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Focused psychosocial interventions for children in low-resource humanitarian settings: a systematic review and individual participant data meta-analysis.

Background: Results from studies evaluating the effectiveness of focused psychosocial support interventions in children exposed to traumatic events in humanitarian settings in low-income and middle-income countries have been inconsistent, showing varying results by setting and subgroup (eg, age or gender). We aimed to assess the effectiveness of these interventions, and to explore which children are likely to benefit most. Methods: We did a systematic review and meta-analysis of individual participant data (IPD) from 3143 children recruited to 11 randomised controlled trials of focused psychosocial support interventions versus waiting list. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, PsycArticles, Web of Science, and the main local low-income and middle-income countries (LMICs) databases according to the list of databases relevant to LMIC developed collaboratively by Cochrane and WHO Library, up to November, 2016. We included randomised controlled trials that assessed the effectiveness of focused psychosocial support interventions in children exposed to traumatic events in LMICs, compared with waiting lists (eg, inactive controls). We excluded quasi-randomised trials, studies that did not focus on psychosocial support interventions, and studies that compared two active interventions without control conditions. We requested anonymised data from each trial for each of the prespecified variables for each child who was randomly assigned. The main outcomes considered were continuous scores in post-traumatic stress disorder (PTSD) symptoms, depressive symptoms, and anxiety symptoms assessed with rating scales administered immediately (0-4 weeks) after the intervention. We harmonised all individual items from rating scales using item response theory methods. This study is registered with PROSPERO, number CRD42013006960. Findings: We identified a beneficial effect of focused psychosocial support interventions on PTSD symptoms (standardised mean difference [SMD] -0·33, 95% CI -0·52 to -0·14) that was maintained at follow-up (-0·21, -0·42 to -0·01). We also identified benefits at the endpoint for functional impairment (-0·29, -0·43 to -0·15) and for strengths: coping (-0·22, -0·43 to -0·02), hope (-0·29, -0·48 to -0·09), and social support (-0·27, -0·52 to -0·02). In IPD meta-analyses focused on age, gender, displacement status, region, and household size we found a stronger improvement in PTSD symptoms in children aged 15-18 years (-0·43, -0·63 to -0·23), in non-displaced children (-0·40, -0·52 to -0·27), and in children living in smaller households (<6 members; -0·27, -0·42 to -0·11). Interpretation: Overall, focused psychosocial interventions are effective in reducing PTSD and functional impairment, and in increasing hope, coping, and social support. Future studies should focus on strengthening interventions for younger children, displaced children, and children living in larger households. Funding: European Commission FP7th Framework Programme for Research (Marie Curie International Outgoing Fellowship) and the National Institute on Aging.

The Lancet. Global health · meta-analysis · 99 citationsread the source →

Prevalence and factors associated with adolescent pregnancies in Zambia: a systematic review from 2000-2022.

Background: Adolescent pregnancy increases risk of short- and long-term adverse social and health outcomes for the adolescent mother and child. Zambia has high prevalence rates of adolescent pregnancy. However, the risk factors are varied and in need of further review and research. The study accordingly reviewed the prevalence and factors associated with adolescent pregnancy in Zambia. Methods: This systematic review was conducted following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The review included original peer-reviewed research articles published from 2000 onwards in English, retrieved from Medline, EMBASE, CINAHL, and African Journals Online databases. Thematic synthesis was used in the analysis of the data extracted from the included studies. Results: Six research studies carried out in Zambia (two quantitative, two qualitative, and two mixed methods) were reviewed and included. Prevalence of adolescent pregnancy in Zambia ranged from 29 to 48%. Additionally, it was found that 29.1% of the country's adolescents, nationally, had given birth as of 2018. Factors at an individual's level such as early or child marriage, exposure to media, knowledge about sexual and reproductive health (SRH) and contraception, contraceptive use, as well as risky sexual behaviours were found to be significantly associated with adolescent pregnancy. Peer pressure, educational attainment, household wealth, and the power dynamics of the household head were identified as the major socio-economic factors alongside socio-cultural, gender and sexual norms amongst other environmental and contextual factors. Policy level factors identified were lack and limited access to SRH information and services by adolescents, including an enabling legal environment. Conclusion: From the review, it was abundantly clear that a combination of individual, interpersonal, environmental, and an enabling legal/policy level factors significantly contribute to the high levels of adolescent pregnancy. There is a paucity of empirical research on the prevalence and determinants of adolescent pregnancy, which suggests an imperative need for large multi-site mixed methods studies to properly explore these and other determinants on a national scale, as well as the long-term implications of these pregnancies on adolescent mothers and babies. Multifaceted and multisectoral interventions which include improved access to education, economic empowerment, addressing gender and socio-cultural norms, should be implemented having due regard to the socio-cultural context which should ride on strong political will, failing which adolescent girls in Zambia will definitely be left behind.

Archives of public health = Archives belges de sante publique · systematic review · 14 citationsread the source →

Efficacy and cost-effectiveness of therapist-guided internet cognitive behavioural therapy for paediatric anxiety disorders: a single-centre, single-blind, randomised controlled trial.

Background: Paediatric anxiety disorders are associated with substantial disability and long-term adverse consequences, but only a small proportion of affected children have access to evidence-based treatment. Internet-delivered cognitive behavioural therapy (ICBT) could help increase accessibility but needs further rigorous assessment. We aimed to assess the efficacy and cost-effectiveness of ICBT in the treatment of paediatric anxiety disorders. Methods: We did a single-blind randomised controlled trial in a clinical research unit within the Child and Adolescent Mental Health Services in Stockholm (Sweden). Eligible participants were children aged 8-12 years with a diagnosis of a principal anxiety disorder (seperation anxiety disorder, generalised anxiety disorder, specific phobia, social anxiety disorder, or panic disorder) of at least moderate severity. We randomly allocated participants (1:1) to ICBT or internet-delivered child-directed play, an active comparator aimed to improve parent-child relationships and increase a child's self-esteem without directly targeting anxiety. Block sizes for the randomisation varied between four and six and were generated using a computer random-number generator, and the allocation was concealed from the researchers by opaque sealed envelopes. Both treatment programmes comprised 12 modules presented over 12 weeks with weekly asynchronous online therapist support, and consisted of texts, films, illustrations, and exercises. The primary outcome was severity rating of the principal anxiety disorder 12-weeks post-treatment, via the Anxiety Disorder Interview Schedule for Diagnostic and Statistical Manual of Mental Disorders-IV (a rating of at least 4 corresponds to meeting the criteria for the principal diagnosis), assessed by clinicians masked to treatment allocation. All participants were included in the primary analysis (intention-to-treat). This trial is registered at ClinicalTrials.gov, number NCT02350257. Findings: Between March 11, 2015, and Oct 21, 2016, 131 participants were recruited and allocated to either ICBT (n=66) or internet-delivered child-directed play (n=65). The clinician-assessed severity rating of the principal anxiety disorder improved significantly after the 12-weeks treatment period for participants in both ICBT (within-group effect size 1·22, 95% CI 0·78-1·65) and the active control (0·72, 0·44-1·00) groups. However, greater improvement was seen with ICBT than with the active control (estimated mean difference 0·79, 95% CI 0·42-1·16, p=0·002; between-group effect size 0·77, 95% CI 0·40-1·15). 29 (48%) participants in the ICBT group no longer had their principal diagnosis, compared to nine (15%) in the active control group (odds ratio 5·41, 95% CI 2·26 to 12·90, p<0·0001); the number needed to treat for ICBT to gain one additional participant in remission was three (95% CI 2·85 to 3·15). ICBT resulted in an average societal-cost saving of €493·05 (95% CI 477·17 to 508·92) per participant. No severe adverse events were reported. Interpretation: ICBT is an efficacious and cost-effective treatment for paediatric anxiety disorders that should be considered for implementation in routine clinical care. Funding: The Swedish Research Council for Health, Working Life and Welfare, and Stockholm County Council.

The Lancet. Child & adolescent health · randomised controlled trial · 51 citationsread the source →

Clinical trial: A Mediterranean diet is feasible and improves gastrointestinal and psychological symptoms in irritable bowel syndrome.

Background: Diet is fundamental to the care of irritable bowel syndrome (IBS). However, some approaches are not appropriate for individuals experiencing psychological symptoms. Aims: To assess feasibility of a Mediterranean diet in IBS and its impact on gastrointestinal and psychological symptoms. Methods: We recruited adults with Rome IV IBS and mild or moderate anxiety and/or depressive symptoms to an unblinded 6-week randomised controlled trial. Patients were randomised to Mediterranean diet counselling or habitual diet. We collected gastrointestinal and psychological symptom data, dietary data and stool samples for metagenomic sequencing. Results: We randomised 59 individuals (29 Mediterranean diet, 30 control); 48 completed the study. The Mediterranean Diet Adherence Screener score was higher in the Mediterranean diet group than controls at week 6 (7.5 [95% CI: 6.9-8.0] vs. 5.7 [5.2-6.3], p < 0.001), and there was a greater score increase than controls (2.1 [95% CI: 1.3-2.9] vs. 0.5 [95% CI: 0.1-1.0], p = 0.004), demonstrating Mediterranean diet feasibility. There was a greater proportion of gastrointestinal symptom responders in the Mediterranean diet group than controls (24/29, 83% vs. 11/30, 37%, p < 0.001) and depression responders (15/29, 52% vs. 6/30 20%, p = 0.015). There was no difference in FODMAP intake at week 6 (p = 0.51). Gastrointestinal adverse events were similar (p = 0.588). There were no differences in change in microbiome parameters between groups. Conclusions: A Mediterranean diet is feasible in IBS and leads to improvement in gastrointestinal and psychological symptoms. Although this study was unblinded, these findings together with the broader benefits of the Mediterranean diet, provide strong impetus for future research in IBS. Australia New Zealand Clinical Trials Registry: ACTRN12620001362987.

Alimentary pharmacology & therapeutics · randomised controlled trial · 44 citationsread the source →

Kleine-Levin syndrome: a systematic review of 186 cases in the literature.

Kleine-Levin syndrome (KLS) is a rare disorder with symptoms that include periodic hypersomnia, cognitive and behavioural disturbances. Large series of patients are lacking. In order to report on various KLS symptoms, identify risk factors and analyse treatment response, we performed a systematic review of 195 articles, written in English and non-English languages, which are available on Medline dating from 1962 to 2004. Doubtful or duplicate cases, case series without individual details and reviews (n = 56 articles) were excluded. In addition, the details of 186 patients from 139 articles were compiled. Primary KLS cases (n = 168) were found mostly in men (68%) and occurred sporadically worldwide. The median age of onset was 15 years (range 4-82 years, 81% during the second decade) and the syndrome lasted 8 years, with seven episodes of 10 days, recurring every 3.5 months (median values) with the disease lasting longer in women and in patients with less frequent episodes during the first year. It was precipitated most frequently by infections (38.2%), head trauma (9%), or alcohol consumption (5.4%). Common symptoms were hypersomnia (100%), cognitive changes (96%, including a specific feeling of derealization), eating disturbances (80%), hypersexuality (43%), compulsions (29%), and depressed mood (48%). In 75 treated patients (213 trials), somnolence decreased using stimulants (mainly amphetamines) in 40% of cases, while neuroleptics and antidepressants were of poor benefit. Only lithium (but not carbamazepine or other antiepileptics) had a higher reported response rate (41%) for stopping relapses when compared to medical abstention (19%). Secondary KLS (n = 18) patients were older and had more frequent and longer episodes, but had clinical symptoms and treatment responses similar to primary cases. In conclusion, KLS is a unique disease which may be more severe in female and secondary cases.

Brain : a journal of neurology · systematic review · 166 citationsread the source →

The effect of comprehensive lifestyle intervention or metformin on obesity in young women.

Background and aim: Young women are at high risk of weight gain but few weight management interventions have been investigated in this group. This study aimed to determine the effect of metformin on body weight, body composition, metabolic risk factors and reproductive hormone levels in overweight or obese young women compared to placebo and comprehensive lifestyle intervention. Methods and results: 203 overweight or obese young women (BMI 33.2+/-0.3 kg/m², age 28+/-0.3 years) were randomised to 1500 mg/day metformin (M) plus general lifestyle advice, placebo (P) plus general lifestyle advice or comprehensive lifestyle intervention including structured diet, exercise and behavioural therapy (L) for 12-weeks. At 12-weeks, linear mixed models found that L group had greater weight loss (-4.2+/-0.4 kg) compared to M (-1.0+/-0.4 kg) and P groups (-0.2+/-0.3 kg) (P < 0.0001). Weight loss between M and P groups were not significantly different. Attrition rate was 48% for L, 34% for M and 29% for P (P = 0.08). Intention-to-treat analysis showed that 10% (8/79) of the subjects in P group had gained weight (>3%), compared to 3% (2/65) from M group and none (0/59) from L group (P < 0.001). The L group had the greatest decrease in waist circumference (-5.2+/-0.7 cm) and fat mass (-5.4+/-0.7 kg) compared to the other groups (P < 0.05). No significant time-by-group effects were seen in plasma lipids, SHBG, testosterone, blood pressure, serum folate, serum ferritin and serum vitamin B12. Conclusion: Lifestyle intervention was more effective in reducing body weight and improving body composition compared to metformin among healthy overweight or obese young women.

Nutrition, metabolism, and cardiovascular diseases : NMCD · randomised controlled trial · 24 citationsread the source →

The psychiatric sequelae of the COVID-19 pandemic in adolescents, adults, and health care workers.

Background: The COVID-19 pandemic is the most serious global public health crisis since the 1918 influenza pandemic. This study is the first to assess its mental health impact across the lifespan in the United States in adolescents, adults, and health care workers. Methods: We recruited 4909 participants through an online survey advertising on Facebook and Instagram to assess exposure to COVID-19 and psychiatric symptoms from April 27 to July 13. We also recruited through the University of Pittsburgh, University of Pittsburgh Medical Center, and other health care systems around Pittsburgh. The primary outcomes were clinically significant depression, anxiety, and posttraumatic stress disorder (PTSD) symptoms, suicidal ideation or behavior, and grief reactions since COVID-19. Results: Adolescents were significantly more likely to report moderate to severe symptoms of depression (55% vs. 29%; χ2  = 122, df = 1; p < .001), anxiety (48% vs. 29%; χ2  = 73; df = 1; p < .001), PTSD (45% vs. 33%; χ2  = 12; df = 1; p < .001), suicidal ideation or behavior (38% vs. 16%; χ2  = 117; df = 1; p < .001), and sleep problems (69% vs. 57%; χ2  = 26; df = 1; p < .001) compared to adults. The rates of intense grief reactions among those who lost someone to COVID-19 was 55%. Loneliness was the most common predictor across outcomes and higher number of hours spent on social media and exposure to media about COVID-19 predicted depression symptoms and suicidal ideation or behavior in adolescents. Conclusions: The COVID-19 pandemic is associated with increased rates of clinically significant psychiatric symptoms. Loneliness could put individuals at increased risk for the onset of psychiatric disorders.

Depression and anxiety · 157 citationsread the source →

The effects of heart rate variability biofeedback in patients with preterm labour.

Preterm birth is a highly prevalent phenomenon that was shown to be associated with mental stress during pregnancy (Rich-Edwards and Grizzard in Am J Obstet Gynecol 192(5 Suppl):S30-S35, 2005). We aimed to assess the effects of heart rate variability (HRV)-biofeedback in patients with preterm labour. Therefore, we conducted a controlled randomized parallel group study in 48 female patients aged 19-38 years (median = 29) with preterm labour at gestational week 24th-32nd (median = 29th). In this study, one group (n = 24) attended six sessions of HRV-biofeedback over 2 weeks whereas patients of the other group (n = 24) were assigned to control sessions. In the HRV-biofeedback treated group, perception of chronic stress was decreased 4 weeks after completion of training compared to baseline (p < 0.05) but there was no change in the control group. In the HRV-biofeedback group, preterm birth was seen in 3 patients (13 %) whereas in the control group, preterm delivery occurred in 8 patients (33 %, p = n.s.). There was no difference in birth weight between groups and HRV remained unchanged. In conclusion, our study demonstrates that HRV-biofeedback can reduce chronic stress in patients with preterm labour when administered as an adjunct to routine care. However, it remains unclear whether stress reduction through HRV-biofeedback has a beneficial effect on preterm birth.

Applied psychophysiology and biofeedback · randomised controlled trial · 15 citationsread the source →

Digital health and telehealth in cancer care: a scoping review of reviews.

The COVID-19 pandemic necessitated remote cancer care delivery via the internet and telephone, rapidly accelerating an already growing care delivery model and associated research. This scoping review of reviews characterised the peer-reviewed literature reviews on digital health and telehealth interventions in cancer published from database inception up to May 1, 2022, from PubMed, Cumulated Index to Nursing and Allied Health Literature, PsycINFO, Cochrane Reviews, and Web of Science. Eligible reviews conducted a systematic literature search. Data were extracted in duplicate via a pre-defined online survey. Following screening, 134 reviews met the eligibility criteria. 77 of those reviews were published since 2020. 128 reviews summarised interventions intended for patients, 18 addressed family caregivers, and five addressed health-care providers. 56 reviews did not target a specific phase of the cancer continuum, whereas 48 reviews tended to address the active treatment phase. 29 reviews included a meta-analysis, with results showing positive effects on quality of life, psychological outcomes, and screening behaviours. 83 reviews did not report intervention implementation outcomes but when reported, 36 reported acceptability, 32 feasibility, and 29 fidelity outcomes. Several notable gaps were identified in these literature reviews on digital health and telehealth in cancer care. No reviews specifically addressed older adults, bereavement, or sustainability of interventions and only two reviews focused on comparing telehealth to in-person interventions. Addressing these gaps with rigorous systematic reviews might help guide continued innovation in remote cancer care, particularly for older adults and bereaved families, and integrate and sustain these interventions within oncology.

The Lancet. Digital health · review · 162 citationsread the source →

Leveraging social capital: multilevel stigma, associated HIV vulnerabilities, and social resilience strategies among transgender women in Lima, Peru.

Introduction: In Peru, transgender women (TW) experience unique vulnerabilities for HIV infection due to factors that limit access to, and quality of, HIV prevention, treatment and care services. Yet, despite recent advances in understanding factors associated with HIV vulnerability among TW globally, limited scholarship has examined how Peruvian TW cope with this reality and how existing community-level resilience strategies are enacted despite pervasive social and economic exclusion facing the community. Addressing this need, our study applies the understanding of social capital as a social determinant of health and examines its relationship to HIV vulnerabilities to TW in Peru. Methods: Using qualitative methodology to provide an in-depth portrait, we assessed (1) intersections between social marginalization, social capital and HIV vulnerabilities; and (2) community-level resilience strategies employed by TW to buffer against social marginalization and to link to needed HIV-related services in Peru. Between January and February 2015, 48 TW participated (mean age = 29, range = 18-44) in this study that included focus group discussions and demographic surveys. Analyses were guided by an immersion crystallization approach and all coding was conducted using Dedoose Version 6.1.18. Results: Themes associated with HIV vulnerability included experiences of multilevel stigma and limited occupational opportunities that placed TW at risk for, and limited their engagement with, existing HIV services. Emergent resiliency-based strategies included peer-to-peer and intergenerational knowledge sharing, supportive clinical services (e.g. group-based clinic attendance) and emotional support through social cohesion (i.e. feeling part of a community). Conclusion: This study highlights the importance of TW communities as support structures that create and deploy social resiliency-based strategies aimed at deterring and mitigating the impact of social vulnerabilities to discrimination, marginalization and HIV risk for individual TW in Peru. Public health strategies seeking to provide HIV prevention, treatment and care for this population will benefit from recognizing existing social capital within TW communities and incorporating its strengths within HIV prevention interventions. At the intersection of HIV vulnerabilities and collective agency, dimensions of bridging and bonding social capital emerged as resiliency strategies used by TW to access needed healthcare services in Peru. Fostering TW solidarity and peer support are key components to ensure acceptability and sustainability of HIV prevention and promotion efforts.

Journal of the International AIDS Society · 68 citationsread the source →

Health system and community level interventions for improving antenatal care coverage and health outcomes.

Background: The World Health Organization (WHO) recommends at least four antenatal care (ANC) visits for all pregnant women. Almost half of pregnant women worldwide, and especially in developing countries do not receive this amount of care. Poor attendance of ANC is associated with delivery of low birthweight babies and more neonatal deaths. ANC may include education on nutrition, potential problems with pregnancy or childbirth, child care and prevention or detection of disease during pregnancy. This review focused on community-based interventions and health systems-related interventions. Objectives: To assess the effects of health system and community interventions for improving coverage of antenatal care and other perinatal health outcomes. Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (7 June 2015) and reference lists of retrieved studies. Selection criteria: We included randomised controlled trials (RCTs), quasi-randomised trials and cluster-randomised trials. Trials of any interventions to improve ANC coverage were eligible for inclusion. Trials were also eligible if they targeted specific and related outcomes, such as maternal or perinatal death, but also reported ANC coverage. Data collection and analysis: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Main results: We included 34 trials involving approximately 400,000 women. Some trials tested community-based interventions to improve uptake of antenatal care (media campaigns, education or financial incentives for pregnant women), while other trials looked at health systems interventions (home visits for pregnant women or equipment for clinics). Most trials took place in low- and middle-income countries, and 29 of the 34 trials used a cluster-randomised design. We assessed 30 of the 34 trials as of low or unclear overall risk of bias. Comparison 1: One intervention versus no interventionWe found marginal improvements in ANC coverage of at least four visits (average odds ratio (OR) 1.11, 95% confidence interval (CI) 1.01 to 1.22; participants = 45,022; studies = 10; Heterogeneity: Tau² = 0.01; I² = 52%; high quality evidence). Sensitivity analysis with a more conservative intra-cluster correlation co-efficient (ICC) gave similar marginal results. Excluding one study at high risk of bias shifted the marginal pooled estimate towards no effect. There was no effect on pregnancy-related deaths (average OR 0.69, 95% CI 0.45 to 1.08; participants = 114,930; studies = 10; Heterogeneity: Tau² = 0.00; I² = 0%; low quality evidence), perinatal mortality (average OR 0.98, 95% CI 0.90 to 1.07; studies = 15; Heterogeneity: Tau² = 0.01; I² = 58%; moderate quality evidence) or low birthweight (average OR 0.94, 95% CI 0.82 to 1.06; studies = five; Heterogeneity: Tau² = 0.00; I² = 5%; high quality evidence). Single interventions led to marginal improvements in the number of women who delivered in health facilities (average OR 1.08, 95% CI 1.02 to 1.15; studies = 10; Heterogeneity: Tau² = 0.00; I² = 0%; high quality evidence), and in the proportion of women who had at least one ANC visit (average OR 1.68, 95% CI 1.02 to 2.79; studies = six; Heterogeneity: Tau² = 0.24; I² = 76%; moderate quality evidence). Results for ANC coverage (at least four and at least one visit) and for perinatal mortality had substantial statistical heterogeneity. Single interventions did not improve the proportion of women receiving tetanus protection (average OR 1.03, 95% CI 0.92 to 1.15; studies = 8; Heterogeneity: Tau² = 0.01; I² = 57%). No study reported onintermittent prophylactic treatment for malaria. Comparison 2: Two or more interventions versus no interventionWe found no improvements in ANC coverage of four or more visits (average OR 1.48, 95% CI 0.99 to 2.21; participants = 7840; studies = six; Heterogeneity: Tau² = 0.10; I² = 48%; low quality evidence) or pregnancy-related deaths (average OR 0.70, 95% CI 0.39 to 1.26; participants = 13,756; studies = three; Heterogeneity: Tau² = 0.00; I² = 0%; moderate quality evidence). However, combined interventions led to improvements in ANC coverage of at least one visit (average OR 1.79, 95% CI 1.47 to 2.17; studies = five; Heterogeneity: Tau² = 0.00; I² = 0%; moderate quality evidence), perinatal mortality (average OR 0.74, 95% CI 0.57 to 0.95; studies = five; Heterogeneity: Tau² = 0.06; I² = 83%; moderate quality evidence) and low birthweight (average OR 0.61, 95% CI 0.46 to 0.80; studies = two; Heterogeneity: Tau² = 0.00; I² = 0%; moderate quality evidence). Meta-analyses for both ANC coverage four or more visits and perinatal mortality had substantial statistical heterogeneity. Combined interventions improved the proportion of women who had tetanus protection (average OR 1.48, 95% CI 1.18 to 1.87; studies = 3; Heterogeneity: Tau² = 0.01; I² = 33%). No trial in this comparison reported on intermittent prophylactic treatment for malaria. Comparison 3: Two interventions compared head to head. No trials found. Comparison 4: One intervention versus a combination of interventionsThere was no difference in ANC coverage (four or more visits and at least one visit), pregnancy-related deaths, deliveries in a health facility or perinatal mortality. No trials in this comparison reported on low birthweight orintermittent prophylactic treatment of malaria. Authors' conclusions: Implications for practice - Single interventions may improve ANC coverage (at least one visit and four or more visits) and deliveries in health facilities. Combined interventions may improve ANC coverage (at least one visit), reduce perinatal mortality and reduce the occurrence of low birthweight. The effects of the interventions are unrelated to whether they are community or health system interventions. Implications for research - More details should be provided in reporting numbers of events, group totals and the ICCs used to adjust for cluster effects. Outcomes should be reported uniformly so that they are comparable to commonly-used population indicators. We recommend further cluster-RCTs of pregnant women and women in their reproductive years, using combinations of interventions and looking at outcomes that are important to pregnant women, such as maternal and perinatal morbidity and mortality, alongside the explanatory outcomes along the pathway of care: ANC coverage, the services provided during ANC and deliveries in health facilities.

The Cochrane database of systematic reviews · meta-analysis · 117 citationsread the source →

Music interventions for acquired brain injury.

Background: Acquired brain injury (ABI) can result in impairments in motor function, language, cognition, and sensory processing, and in emotional disturbances, which can severely reduce a survivor's quality of life. Music interventions have been used in rehabilitation to stimulate brain functions involved in movement, cognition, speech, emotions, and sensory perceptions. An update of the systematic review published in 2010 was needed to gauge the efficacy of music interventions in rehabilitation for people with ABI. Objectives: To assess the effects of music interventions for functional outcomes in people with ABI. We expanded the criteria of our existing review to: 1) examine the efficacy of music interventions in addressing recovery in people with ABI including gait, upper extremity function, communication, mood and emotions, cognitive functioning, social skills, pain, behavioural outcomes, activities of daily living, and adverse events; 2) compare the efficacy of music interventions and standard care with a) standard care alone, b) standard care and placebo treatments, or c) standard care and other therapies; 3) compare the efficacy of different types of music interventions (music therapy delivered by trained music therapists versus music interventions delivered by other professionals). Search methods: We searched the Cochrane Stroke Group Trials Register (January 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 6), MEDLINE (1946 to June 2015), Embase (1980 to June 2015), CINAHL (1982 to June 2015), PsycINFO (1806 to June 2015), LILACS (1982 to January 2016), and AMED (1985 to June 2015). We handsearched music therapy journals and conference proceedings, searched dissertation and specialist music databases, trials and research registers, reference lists, and contacted relevant experts and music therapy associations to identify unpublished research. We imposed no language restriction. We performed the original search in 2009. Selection criteria: We included all randomised controlled trials and controlled clinical trials that compared music interventions and standard care with standard care alone or combined with other therapies. We examined studies that included people older than 16 years of age who had ABI of a non-degenerative nature and were participating in treatment programmes offered in hospital, outpatient, or community settings. We included studies in any language, published and unpublished. Data collection and analysis: Two review authors independently extracted data and assessed the risk of bias of the included studies. We contacted trial researchers to obtain missing data or for additional information when necessary. Where possible, we presented results for continuous outcomes in meta-analyses using mean differences (MDs) and standardised mean differences (SMDs). We used post-test scores. In cases of significant baseline difference, we used change scores. We conducted a sensitivity analysis to assess the impact of the randomisation method. Main results: We identified 22 new studies for this update. The evidence for this update is based on 29 trials involving 775 participants. A music intervention known as rhythmic auditory stimulation may be beneficial for improving the following gait parameters after stroke. We found a reported increase in gait velocity of 11.34 metres per minute (95% confidence interval (CI) 8.40 to 14.28; 9 trials; 268 participants; P < 0.00001; moderate-quality evidence). Stride length of the affected side may also benefit, with a reported average of 0.12 metres more (95% CI 0.04 to 0.20; 5 trials; 129 participants; P = 0.003; moderate-quality evidence). We found a reported average improvement for general gait of 7.67 units on the Dynamic Gait Index (95% CI 5.67 to 9.67; 2 trials; 48 participants; P < 0.00001). There may also be an improvement in gait cadence, with a reported average increase of 10.77 steps per minute (95% CI 4.36 to 17.18; 7 trials; 223 participants; P = 0.001; low-quality evidence).Music interventions may be beneficial for improving the timing of upper extremity function after stroke as scored by a reduction of 1.08 seconds on the Wolf Motor Function Test (95% CI -1.69 to -0.47; 2 trials; 122 participants; very low-quality evidence).Music interventions may be beneficial for communication outcomes in people with aphasia following stroke. Overall, communication improved by 0.75 standard deviations in the intervention group, a moderate effect (95% CI 0.11 to 1.39; 3 trials; 67 participants; P = 0.02; very low-quality evidence). Naming was reported as improving by 9.79 units on the Aachen Aphasia Test (95% CI 1.37 to 18.21; 2 trials; 35 participants; P = 0.02). Music interventions may have a beneficial effect on speech repetition, reported as an average increase of 8.90 score on the Aachen Aphasia Test (95% CI 3.25 to 14.55; 2 trials; 35 participants; P = 0.002).There may be an improvement in quality of life following stroke using rhythmic auditory stimulation, reported at 0.89 standard deviations improvement on the Stroke Specific Quality of Life Scale, which is considered to be a large effect (95% CI 0.32 to 1.46; 2 trials; 53 participants; P = 0.002; low-quality evidence). We found no strong evidence for effects on memory and attention. Data were insufficient to examine the effect of music interventions on other outcomes. The majority of studies included in this review update presented a high risk of bias, therefore the quality of the evidence is low. Authors' conclusions: Music interventions may be beneficial for gait, the timing of upper extremity function, communication outcomes, and quality of life after stroke. These results are encouraging, but more high-quality randomised controlled trials are needed on all outcomes before recommendations can be made for clinical practice.

The Cochrane database of systematic reviews · meta-analysis · 116 citationsread the source →

Interventions for the treatment of metastatic extradural spinal cord compression in adults.

Background: Metastatic extradural spinal cord compression (MESCC) is treated with radiotherapy, corticosteroids, and surgery, but there is uncertainty regarding their comparative effects. This is an updated version of the original Cochrane review published in theCochrane Database of Systematic Reviews (Issue 4, 2008). Objectives: To determine the efficacy and safety of radiotherapy, surgery and corticosteroids in MESCC. Search methods: In March 2015, we updated previous searches (July 2008 and December 2013) of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, LILACS, CANCERLIT, clinical trials registries, conference proceedings, and references, without language restrictions. We also contacted experts for relevant published, unpublished and ongoing trials. Selection criteria: Randomised controlled trials (RCTs) of radiotherapy, surgery and corticosteroids in adults with MESCC. Data collection and analysis: Three authors independently screened and selected trials, assessed risk of bias, and extracted data. We sought clarifications from trial authors. Where possible, we pooled relative risks with their 95% confidence intervals, using a random effects model if heterogeneity was significant. We assessed overall evidence-quality using the GRADE approach. Main results: This update includes seven trials involving 876 (723 evaluable) adult participants (19 to 87 years) in high-income countries. Most were free of the risk of bias. Different radiotherapy doses and schedulesTwo equivalence trials in people with MESCC and a poor prognosis evaluated different radiotherapy doses and schedules. In one, a single dose (8 Gray (Gy)) of radiotherapy (RT) was as effective as short-course RT (16 Gy in two fractions over one week) in enhancing ambulation in the short term (65% versus 69%; risk ratio (RR) was 0.93, (95% confidence interval (CI) 0.82 to 1.04); 303 participants; moderate quality evidence). The regimens were also equally effective in reducing analgesic and narcotic use (34% versus 40%; RR 0.85, 95% CI 0.62 to 1.16; 271 participants), and in maintaining urinary continence (90% versus 87%; RR 1.03, 95% CI 0.96 to 1.1; 303 participants) in the short term (moderate quality evidence). In the other trial, split-course RT (30 Gy in eight fractions over two weeks) was no different from short-course RT in enhancing ambulation (70% versus 68%; RR 1.02, 95% CI 0.9 to 1.15; 276 participants); reducing analgesic and narcotic use (49% versus 38%; RR 1.27, 95% CI 0.96 to 1.67; 262 participants); and in maintaining urinary continence (87% versus 90%; RR 0.97, 0.93 to 1.02; 275 participants) in the short term (moderate quality evidence). Median survival was similar with the three RT regimens (four months). Local tumour recurrence may be more common with single-dose compared to short-course RT (6% versus 3%; RR 2.21, 95% CI 0.69 to 7.01; 303 participants) and with short-course compared to split-course RT (4% versus 0%; RR 0.1, 95% CI 0.01 to 1.72; 276 participants), but these differences were not statistically significant (low quality evidence). Gastrointestinal adverse effects were infrequent with the three RT regimens (moderate quality evidence), and serious adverse events or post-radiotherapy myelopathy were not noted. We did not find trials comparing radiotherapy schedules in people with MESCC and a good prognosis. Surgery plus radiotherapy compared to radiotherapyLaminectomy plus RT offered no advantage over RT in one small trial with 29 participants (very low quality evidence). In another trial that was stopped early for apparent benefit, decompressive surgery plus RT resulted in better ambulatory rates (84% versus 57%; RR 1.48, 95% CI 1.16 to 1.90; 101 participants, low quality evidence). Narcotic use may also be lower, and bladder control may also be maintained longer than with than RT in selected patients (low quality evidence). Median survival was longer after surgery (126 days versus 100 days), but the proportions surviving at one month (94% versus 86%; RR 1.09, 95% CI 0.96 to 1.24; 101 participants) did not differ significantly (low quality evidence). Serious adverse events were not noted. Significant benefits with surgery occurred only in people younger than 65 years. High dose corticosteroids compared to moderate dose or no corticosteroidsData from three small trials suggest that high-dose steroids may not differ from moderate-dose or no corticosteroids in enhancing ambulation (60% versus 55%; RR 1.08, 95% CI 0.81 to 1.45; 3 RCTs, 105 participants); survival over two years (11% versus 10%; RR 1.11, 95% CI 0.24 to 5.05; 1 RCT, 57 participants); pain reduction (78% versus 91%; RR 0.86, 95% CI 0.62 to 1.20; 1 RCT, 25 participants); or urinary continence (63% versus 53%; RR 1.18, 95% CI 0.66 to 2.13; 1 RCT, 34 participants; low quality evidence). Serious adverse effects were more frequent with high-dose corticosteroids (17% versus 0%; RR 8.02, 95% CI 1.03 to 62.37; 2 RCTs, 77 participants; moderate quality evidence).None of the trials reported satisfaction with care or quality of life in participants. Authors' conclusions: Based on current evidence, ambulant adults with MESCC with stable spines and predicted survival of less than six months will probably benefit as much from one dose of radiation (8 Gy) as from two doses (16 Gy) or eight doses (30 Gy). We are unsure if a single dose is as effective as two or more doses in preventing local tumour recurrence. Laminectomy preceding radiotherapy may offer no benefits over radiotherapy alone. Decompressive surgery followed by radiotherapy may benefit ambulant and non-ambulant adults younger than 65 years of age, with poor prognostic factors for radiotherapy, a single area of compression, paraplegia for less than 48 hours, and a predicted survival of more than six months. We are uncertain whether high doses of corticosteroids offer any benefits over moderate doses or indeed no corticosteroids; but high-dose steroids probably significantly increases the risk of serious adverse effects. Early detection; and treatment based on neurological status, age and estimated survival, are crucial with all treatment modalities. Most of the evidence was of low quality. High-quality evidence from more trials is needed to clarify current uncertainties, and some studies are in progress.

The Cochrane database of systematic reviews · meta-analysis · 39 citationsread the source →

Home-based prehabilitation: a systematic review and meta-analysis of randomised trials.

Background: Prehabilitation aims to enhance preoperative functional capacity through exercise, nutrition, and psychological programs. Home-based prehabilitation represents an alternative to hospital prehabilitation, with the advantage of not utilising hospital resources. This review aims to evaluate adherence and clinical effectiveness of home-based prehabilitation. Methods: We searched PubMed, Cochrane, and Embase up to October 1, 2024 for randomised controlled trials comparing home-based prehabilitation with standard care. The primary outcome was the proportion of patients with postoperative complications. Secondary outcomes included protocol adherence, and 6-min walking test. We used risk ratios (RR) and mean differences to summarise the results. The risk of bias was assessed using RoB 2 tool. Results: We included 29 randomised trials for a total of 3508 patients. Median adherence to home-based prehabilitation programs was 82%. Home-based prehabilitation reduced the proportion of patients with postoperative complications (508/1322 [38.4%] vs 578/1335 [43.3%], risk ratio 0.84, 95% confidence interval [CI] 0.72-0.98, P=0.02, I2=44%, low certainty). After home-based prehabilitation, 6-min walking test performance was better compared with control (MD 28.2 m (95% CI 9.5-46.9; P<0.01, I2=48). Preoperative depression (MD -0.65, 95% CI -0.87 to -0.43; P<0.001, I2=0%), postoperative anxiety (MD -0.50, 95% CI -0.75 to -0.25; P<0.001, I2=0%, low certainty) and length of hospital stays (MD -0.32 days, 95% CI -0.61 to -0.03; P=0.03, I2=45%, low certainty) were lower with home-based prehabilitation. Conclusions: Home-based prehabilitation reduced the proportion of patients with postoperative complications, but with low certainty of evidence. It also improved preoperative functional capacity, reduced hospital stays, depression and anxiety scores, with good adherence to the intervention. Systematic review protocol: PROSPERO (CRD42024591208).

British journal of anaesthesia · meta-analysis · 18 citationsread the source →

Music interventions for improving psychological and physical outcomes in people with cancer.

Background: This is an update of the review published on the Cochrane Library in 2016, Issue 8. Having cancer may result in extensive emotional, physical and social suffering. Music interventions have been used to alleviate symptoms and treatment side effects in people with cancer. This review includes music interventions defined as music therapy offered by trained music therapists, as well as music medicine, which was defined as listening to pre-recorded music offered by medical staff. Objectives: To assess and compare the effects of music therapy and music medicine interventions for psychological and physical outcomes in people with cancer. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 3) in the Cochrane Library, MEDLINE via Ovid, Embase via Ovid, CINAHL, PsycINFO, LILACS, Science Citation Index, CancerLit, CAIRSS, Proquest Digital Dissertations, ClinicalTrials.gov, Current Controlled Trials, the RILM Abstracts of Music Literature, http://www.wfmt.info/Musictherapyworld/ and the National Research Register. We searched all databases, except for the last two, from their inception to April 2020; the other two are no longer functional, so we searched them until their termination date. We handsearched music therapy journals, reviewed reference lists and contacted experts. There was no language restriction. Selection criteria: We included all randomized and quasi-randomized controlled trials of music interventions for improving psychological and physical outcomes in adults and pediatric patients with cancer. We excluded patients undergoing biopsy and aspiration for diagnostic purposes. Data collection and analysis: Two review authors independently extracted the data and assessed the risk of bias. Where possible, we presented results in meta-analyses using mean differences and standardized mean differences. We used post-test scores. In cases of significant baseline difference, we used change scores. We conducted separate meta-analyses for studies with adult participants and those with pediatric participants. Primary outcomes of interest included psychological outcomes and physical symptoms and secondary outcomes included physiological responses, physical functioning, anesthetic and analgesic intake, length of hospitalization, social and spiritual support, communication, and quality of life (QoL) . We used GRADE to assess the certainty of the evidence. Main results: We identified 29 new trials for inclusion in this update. In total, the evidence of this review rests on 81 trials with a total of 5576 participants. Of the 81 trials, 74 trials included adult (N = 5306) and seven trials included pediatric (N = 270) oncology patients. We categorized 38 trials as music therapy trials and 43 as music medicine trials. The interventions were compared to standard care. Psychological outcomes The results suggest that music interventions may have a large anxiety-reducing effect in adults with cancer, with a reported average anxiety reduction of 7.73 units (17 studies, 1381 participants; 95% confidence interval (CI) -10.02 to -5.44; very low-certainty evidence) on the Spielberger State Anxiety Inventory scale (range 20 to 80; lower values reflect lower anxiety). Results also suggested a moderately strong, positive impact of music interventions on depression in adults (12 studies, 1021 participants; standardized mean difference (SMD): -0.41, 95% CI -0.67 to -0.15; very low-certainty evidence). We found no support for an effect of music interventions on mood (SMD 0.47, 95% CI -0.02 to 0.97; 5 studies, 236 participants; very low-certainty evidence). Music interventions may increase hope in adults with cancer, with a reported average increase of 3.19 units (95% CI 0.12 to 6.25) on the Herth Hope Index (range 12 to 48; higher scores reflect greater hope), but this finding was based on only two studies (N = 53 participants; very low-certainty evidence). Physical outcomes We found a moderate pain-reducing effect of music interventions (SMD -0.67, 95% CI -1.07 to -0.26; 12 studies, 632 adult participants; very low-certainty evidence). In addition, music interventions had a small treatment effect on fatigue (SMD -0.28, 95% CI -0.46 to -0.10; 10 studies, 498 adult participants; low-certainty evidence). The results suggest a large effect of music interventions on adult participants' QoL, but the results were highly inconsistent across studies, and the pooled effect size was accompanied by a large confidence interval (SMD 0.88, 95% CI -0.31 to 2.08; 7 studies, 573 participants; evidence is very uncertain). Removal of studies that used improper randomization methods resulted in a moderate effect size that was less heterogeneous (SMD 0.47, 95% CI 0.06 to 0.88, P = 0.02, I2 = 56%). A small number of trials included pediatric oncology participants. The findings suggest that music interventions may reduce anxiety but this finding was based on only two studies (SMD -0.94, 95% CI -1.9 to 0.03; very low-certainty evidence). Due to the small number of studies, we could not draw conclusions regarding the effects of music interventions on mood, depression, QoL, fatigue or pain in pediatric participants with cancer. The majority of studies included in this review update presented a high risk of bias, and therefore the overall certainty of the evidence is low. For several outcomes (i.e. anxiety, depression, pain, fatigue, and QoL) the beneficial treatment effects were consistent across studies for music therapy interventions delivered by music therapists. In contrast, music medicine interventions resulted in inconsistent treatment effects across studies for these outcomes. Authors' conclusions: This systematic review indicates that music interventions compared to standard care may have beneficial effects on anxiety, depression, hope, pain, and fatigue in adults with cancer. The results of two trials suggest that music interventions may have a beneficial effect on anxiety in children with cancer. Too few trials with pediatric participants were included to draw conclusions about the treatment benefits of music for other outcomes. For several outcomes, music therapy interventions delivered by a trained music therapist led to consistent results across studies and this was not the case for music medicine interventions. Moreover, evidence of effect was found for music therapy interventions for QoL and fatigue but not for music medicine interventions. Most trials were at high risk of bias and low or very low certainty of evidence; therefore, these results need to be interpreted with caution.

The Cochrane database of systematic reviews · systematic review · 144 citationsread the source →

Investigating the efficacy of digital cognitive behavioural therapy in comparison to a sleep-monitoring application via integrated diary and actigraphy: A randomised-controlled trial.

Dissemination of digital cognitive behavioural therapy is a promising approach for treating insomnia in the broad population. Current evidence supports the effectiveness of the digital format, but clinical findings are often limited by the choice of control group and lack of in-depth therapeutic measures. This study was designed to investigate the specific effects of digital cognitive behavioural therapy in comparison to a self-monitoring application. Participants meeting criteria for insomnia were randomly allocated (1:1) to 8 weeks of digital cognitive behavioural therapy or 8 weeks of digital sleep monitoring (control application). The primary outcome, insomnia severity, was assessed at baseline, 8- and 16-weeks post-randomisation. Secondary outcomes included the assessment of sleep via application-integrated sleep diaries and actigraphy. Linear-mixed models were fitted to assess between-group differences. Fifty-six participants (48 females, mean age: M = 45.55 ± 13.70 years) were randomised to either digital cognitive behavioural therapy (n = 29) or digital sleep monitoring (n = 27). At 8- and 16-weeks post-randomisation, large treatment effects (d = 0.87-1.08) indicated robust reductions (-3.70 and -2.97, respectively; p ≤ 0.003) in insomnia severity in the digital cognitive behavioural therapy arm, relative to digital sleep monitoring. Treatment effects in favour of digital cognitive behavioural therapy were also found for self-reported and actigraphy-derived sleep continuity variables, indicating that sleep improved throughout the 8-week intervention period. Our study reinforces the role of digital cognitive behavioural therapy in achieving clinical improvements for patients with insomnia, affirming previous findings and supporting the specific effects of cognitive behavioural therapy.

Journal of sleep research · randomised controlled trial · 11 citationsread the source →

Does Improving Medical Record Documentation Better Reflect Severity of Illness in Neurosurgical Patients?

Physician documentation in the medical record is essential for communicating the clinical status and care plan to other healthcare providers. The medical record also serves as a medicolegal document to protect the physician should medical malpractice be alleged. In addition to these uses, documentation of patients' diagnoses and procedures is used by hospital coders to calculate severity of illness (SOI) and risk of mortality (ROM) ratings. A rating given from level 1 to 4 (4 being most severe), SOI reflects a patient's degree of physiological illness. Also scored from 1 to 4, ROM is a gauge of the patient's risk of death while in the hospital on the basis of the patient's diagnoses (Table 1).TABLE: 1. Severity of Illness and Risk of Mortality Grading SystemsBoth SOI and ROM have significant roles in healthcare economics. Hospital reimbursement depends in part on SOI. The Centers for Medicare and Medicaid Services (CMS) is the entity of the federal government that is responsible for healthcare financing, coverage, and payment of Medicare and Medicaid beneficiaries. Formerly known as the Health Care Financing Administration, CMS adopted diagnosis-related groups (DRGs) in 1983 after their development at Yale University in 1970. Their purpose was to replace the traditional per-diem method of hospital reimbursement. Per diems were cost based and characterized as an undifferentiated patient day regardless of patient illness. In contrast, each DRG classification represents similar resource consumption and length-of-stay patterns so that reimbursement is based on these expectations. In 2008, the CMS went one step further and added a severity-adjusted version to the original DRGs called Medicare-severity DRG.1 The severity adjustment takes into account the patient's SOI and is now used by the Medicare Inpatient Prospective Payment System. The SOI and ROM scores are also being used to gauge quality control issues. Data for every Medicare inpatient stay are maintained in the Medicare Provider and Analysis Review file.2 Quality improvement organizations contracted by CMS to provide quality oversight to Medicare providers use the data to assess potential problems with noncompliance. Additionally, these organizations analyze a facility's Medicare-severity DRG mix to look for problems with hospitals that may potentially always code for higher-weighted DRGs and appear as outliers compared with other similar facilities.3 Finally, “quality of care” assessments use SOI and ROM. Mortality rates vary between providers and hospitals; the presumption is that after controlling for patients' severity of illness, residual differences in mortality rates relate to differences in quality of care. Corporations such as Thompson Reuters have created a marketing tool and “status” based on this information that hospitals may strive to achieve. The well-known “Top 100 Hospitals”4 lists the 100 “best” hospitals across the country in a given specialty line. When the results of the Hospital Consumer Assessment of Healthcare Providers and Systems survey5 are compared between winners of the Top 100 Hospitals award and nonwinners, the award winners do slightly better than nonwinners on all survey items that showed modest but statistically significant differences between the 2 groups.6 These findings suggest that marketing tools such as the Top 100 Hospitals might play a role in consumer perception, assessment, and decision making. All-patient-refined DRGs (APR-DRGs) are another mode for comparison. Trademarked by 3M, APR-DRGs classify all inpatient admissions based on the SOI and ROM levels represented by International Classification of Disease, ninth revision (ICD-9), codes. Institutions such as the Agency for Healthcare Research and Quality are using APR-DRGs for quality monitoring purposes, especially for severity adjustment of mortality rates.1 The SOI and ROM are derived from documentation of patients' diagnoses and comorbidities.1,7 Errors in documentation can lead to overestimation or underestimation of expected mortality, which has an effect on an institution's comparison with other hospitals.8,9 Furthermore, neurosurgeons contribute significantly to hospitals' financial health.10,11 Better documentation of admitting diagnoses and comorbidities should enable more accurate ICD-9 coding, which in turn should lead to more accurate calculation of SOI and ROM. The rationale for the study stemmed from a need for resident participation in a quality improvement project, a requirement dictated by the Accreditation Council of Graduate Medical Education.12 Before the project, a preliminary review of progress notes on the neurosurgery service by one of the authors (N.S.L.) indicated suboptimal documentation of patient comorbidities. The objective of this study was to determine whether interventions designed to effectively improve physician clinical documentation would subsequently lead to increased capture of SOI and ROM. A secondary aim of the project was to simultaneously provide residents with a quality improvement opportunity. We hypothesize that the multimodality interventions that improve neurosurgeons' clinical documentation lead to better characterization of SOI and ROM. MATERIALS AND METHODS Documentation Improvement Interventions Before data collection, 3 specific interventions were used to educate physicians with the goal of improving medical record documentation as part of the master's thesis of one of the authors (C.H.). These modalities included the following: group in-service, development and use of a progress note template, and concurrent medical record coder review and feedback to the physician during the patients' in-hospital stays. Faculty and residents in the Division of Neurological Surgery at University of Missouri Hospitals and Clinics participated in a 30-minute in-service on coding, SOI, and ROM. A new neurosurgery progress note template (Figure 1) was introduced, and instructions for its use were provided. The template was organized to include comorbidities listed as ICD-9 codes and grouped into organ system for ease of location.FIGURE 1: Neurosurgery progress note. Mechanisms for queries to the physicians from the nurse reviewer and appropriate responses were explained to the group. Informed consent was obtained from the participating physicians. The study was approved by the Health Sciences Institutional Review Board. After the in-service, a nurse-reviewer (working in the capacity of assistant manager of medical records) began random review of neurosurgical patient records. Random record review was performed 2 to 3 times per week, averaging 10 to 15 h/wk, while patients were still hospitalized to look for potential diagnoses that were not appropriately documented. Charts for review were chosen at random; however, intensive care unit patients were given priority for review over floor patients. Information gathered was kept on a worksheet (Figure 2), and cases for which questions existed were e-mailed to the physicians with a copy to the senior author (N.S.L). A typical query follows: “Patient X, MNICU 13, had a 3400cc EBL during OR, and received several units of PRBCx and FFP. H&H dropped from 12.1/35.2 to 5.9/17. Would a secondary diagnosis of acute blood loss anemia be appropriate? If so, please document in the progress notes.”FIGURE 2: Clinical documentation review tool. Follow-up on queries was completed to determine whether the physician had documented the diagnosis in question. If no response was made, a second e-mail was sent. In cases when the patient had been discharged and confirmation or disagreement with the query was not documented in the progress notes as requested, an e-mail notification was sent, asking the physician to address the query in the discharge summary. This method of review, queries by e-mail, and rereview occurred for 8 weeks. Data Collection All neurosurgery service adult in-patient charts at University of Missouri Hospital and Clinics were retrospectively reviewed from 3 time intervals. June 2004 to December 2004 represented the preintervention period. August 2007 to December 2007 was the time period during active educational intervention. Finally, June 2008 to December 2008 represented the postintervention period. Data collected included patient age, sex, ICD-9 diagnoses, raw patient mortality, SOI, and ROM. Patients younger than 18 years of age at the time of admission were excluded. Versions 24 and 25 of the 3M APR-DRGs13,14 were used to calculate ROM and SOI. Preliminary data were pulled from each time period and analyzed according to the description below. From the results of the preliminary data analysis, the standard deviation for the SOI and ROM outcomes was estimated to be about 1.0 units. It was determined that sample sizes of 300 patients per time period would give well over 80% power for detecting differences in mean scores of 0.25 units. The estimated power was found using the POWER procedure in SAS version 9 (SAS Institute Inc, Cary, North Carolina). Data Analysis The outcomes of mortality, SOI, and ROM can all be influenced by a patient's age, sex, and primary diagnosis. Consequently, analyses were done to determine whether any of these variables differed between time periods. Furthermore, these variables were considered covariates when testing the primary outcomes for differences between time periods. Primary diagnoses were grouped into 9 categories based on ICD-9 codes as follows: malignant neoplasms, benign neoplasms, nervous system disorders, cardiovascular disease, musculoskeletal disorders, skull/spine injuries, brain contusions, complications, and other diagnoses. The Kruskal-Wallis test was used to test for differences in age between time periods. Sex differences were assessed with a χ2 model. Stratification or adjustment for differences in age and sex was performed with the Cochran-Mantel-Haenszel test. For the prediction of the probability of occurrence of mortality, logistic regression was used. Finally, the cumulative logit model was used to analyze SOI and ROM, taking into account differences in primary diagnoses over time. The SAS Analytical Software version 9.0 was used for the analysis. In view of the fact that preliminary data were reanalyzed, allowing 2 opportunities to reject the null hypothesis of no group differences, only values of P < .01 were considered significant. RESULTS Chart Review Intervention During the 8-week period of chart review, 53 inpatient charts were reviewed. A total of 99 reviews were completed in total, with 41 queries sent to physicians (41%). All but 2 queries were sent via e-mail. Sixteen second-request queries were sent. Twenty queries (53%) were agreed on and documented in the record. A physician disagreed with 1 query, so no change in documentation was made, and 17 queries yielded no response (44.7%). SOI/ROM Values Over the 3 time periods, 1009 cases were analyzed: 329 patients during the preintervention period, 306 patients during the intervention period, and 374 patients during the post-intervention period. The simple mean values of SOI in the 3 time periods were as follows: 1.72 before intervention, 1.69 during intervention, and 1.82 after intervention (P = .09, χ2). Simple mean values of ROM in each time period were 1.40, 1.43, and 1.56 respectively (P = .02, χ2), with mortality rates of 6.38%, 3.59%, and 5.61% respectively (P = .27, χ2). Raw data results are summarized in Table 2.TABLE: 2. Summary of Raw DataaEffect of Age and Sex on SOI and ROM Mean patient age differed significantly between time periods: 48.3 years of age before intervention, 52.1 years of age during intervention, and 53.1 years of age after intervention (P = .001, Kruskal-Wallis). Accounting for differences in age did not affect SOI (P = .24), ROM (P = .48), and raw mortality (P = .06, Cochran-Mantel-Haenszel). Sex distributions were similar in each time period (P = .64, χ2). Effect of Diagnosis The distribution of diagnoses in each time period is shown in Table 3. Primary diagnosis did not differ significantly between the preintervention and intervention time periods (P = .13), even when adjusted for age and sex (P = .28, Cochran-Mantel-Haenszel). However, when the preintervention and intervention periods were combined and compared with the postintervention period, differences in diagnoses were noted (P < .001, Cochran-Mantel-Haenszel).TABLE: 3. Distributions of Diagnoses Between 3 Time PeriodsIn an effort to account for differences in diagnoses, a statistical compromise had to be achieved between not using primary diagnoses as a covariant and using them with a large number of categories. Therefore, 3 categories were established on the basis of the diagnosis frequency: cardiovascular disease (32 deaths), brain contusion (6 deaths), and other (15 deaths). After diagnosis differences (3 categories) were accounted for with logistic regression, no differences in mortality rate were found between the postintervention period and either the intervention (P = .08) or preintervention (P = .15) period. No significant differences between preintervention and postinterventional periods for SOI (P = .29) or ROM (P = .48) were present when differences in diagnoses were accounted for (cumulative logit model). DISCUSSION Overall, we expected SOI to be lower during the preintervention period and the ROM modified by SOI to be lower during the intervention and postintervention periods. However, despite interventions such as educational in-service, progress note template, and reminders about the possibility of addending progress notes, no differences in SOI or ROM were present during active intervention or in the period after intervention. The lack of impact of intervention on SOI and ROM was not affected by the differences in age or diagnoses present among the 3 time periods. Other studies have shown success with progress note templates. Grogan et al15 focused on improvements to physician documentation and evaluated the effectiveness in terms of ICD-9 coding, APR-DRG, DRG weight, and University Healthcare Consortium-predicted mortality. A progress note template included a section developed by coding specialists with 40 of the most common general surgery comorbidities and complications (in check-box format). A significant increase was found in total ICD-9 codes, template-specific ICD-9 codes, APR-DRG, DRG weight, and University Healthcare Consortium-predicted mortality. Sprtel and Zlabek16 also showed success with the implementation of a progress note template in conjunction with a brief documentation lecture. Their results showed an absolute increase in the highest code by 14.5%, increased billable income by $10 385, and improved resident awareness of documentation. A number of interventions for improvement in documentation and assessment end points have been suggested. Marco and Buchman17 noted that simply asking for private commitment to change can yield measurable results. They obtained in writing acknowledgement that improvement in documentation was necessary and noticed that the acknowledging physicians showed improvement in the percentage of cases with the required documentation over time. As-Sanie et al18 had success with obstetrics/gynecology residents after providing individual instructional sessions with faculty on coding and documentation, whereas Lemen19 also showed success within the same specialty with the assistance of an online module. At the other end of the spectrum, Tinsley20 described the use of a whole multidisciplinary team to improve documentation among psychiatry residents. The team met regularly to clarify resident charting responsibilities, to make the inpatient record a better communication tool, and to consider the various causes of charting deficiencies. Improvement in charting 4 of 5 items (admission note, an off-service note, descriptions of medication changes, daily progress notes, and the name and discipline of the individual recording these items) improved significantly after 1 month of intervention and was maintained at 6 months. Table 4 summarizes these intervention results.TABLE: 4. Summary of Literature ReviewaTime is likely necessary to establish educational interventions that generate long-lasting habits in physicians and improve documentation. Relationships are present between repetition and automaticity of such habits. For instance, in 1 study,33 82 mostly postgraduate students were asked to choose a healthy eating, drinking, or exercise behavior to convert into a daily habit. A self-report habit index34 was used to quantify habit strength. During 12 weeks of active study, 48% of participants reached levels thought to be consistent with habit formation. Further analysis concluded that the time needed for participants to reach 95% of their automaticity ranged from 18 to 254 days (mean, 64 days). The 8 weeks of active intervention in this study may not have been sufficient to allow documentation habits to form fully. Furthermore, educators must also question whether the amount of time required to learn simple habits differs from more complex habits requiring additional planning. Verplanken35 showed that when repetitions are limited, a simple behavior had a higher habit score than a complex behavior. Physician documentation in the setting of demanding schedules and the intricacies of medical coding likely falls into the category of a complex habit. Therefore, physicians' documentation habits promoting better documentation may be on the longer end of the to The effect the number of daily repetitions on the time to automaticity is also This study other that may improvement in documentation. did not to of queries with documentation The physicians would not be to their e-mail in the day or and progress note were not Additionally, physicians may have that an or new note in the medical record for the purpose of to a query was given their other A more of review and physician feedback have to an increase in in the medical record. and medical for diagnoses that were and not appropriately documented is a Over the 8 weeks of the intervention period, 99 reviews on 53 charts were Therefore, of the total neurosurgical admissions during the 8-week period, only of them were reviewed at during their For review and more nurse-reviewer might be required to review a of inpatient charts before significant results can be in improving documentation be that the progress note template was progress note was from Grogan et was modified by a multidisciplinary the of neurosurgical and the assistant manager of medical to include complications and comorbidities typical of neurosurgical patients. No studies were to the of the template in accurate diagnoses. the educational interventions improved medical record documentation, SOI and ROM may not have differed between the 3 time periods for other This study did not assess the level and of the medical Medical coders are by to them on can and codes However, a is required to review and to the clinical between various and common complications with specific for the to documentation to look Documentation of comorbidities and complications on a progress note template might provide more documentation but not more accurate must also consider whether ICD-9 codes are appropriate for SOI and ROM. have found of in codes, on the diagnoses and being After a review of medical from et concluded that coding of diagnosis had an rate of compared with medical record et the of codes for cardiovascular and risk Overall, in Medicare the of codes was whereas the ranged from only to the ICD-9 data to illness, other studies have shown that these can is in disease and For instance, et and the of Health found that an illness of ICD-9 data from a in the with from and ICD-9 codes have been found in of disease to be for is not known whether the same can be for using ICD-9 codes to calculate of SOI and ROM. Interventions to improve documentation by physicians to change SOI or ROM in patients on a neurosurgical these interventions were to make a or coders a amount of and to at documentation to look to improve their quality in to SOI and ROM must be to time and to the of the of these physicians should play an active role in the development and of educational such as physician feedback and chart review all patients on the inpatient service may lead to a more medical record documentation. for this project was by the Division of Neurological Surgery Research The authors have no financial or in any of the or described in this This was based in part on the 2007 master's thesis project by for the University of Missouri Health and are Interventions for Physician Documentation of Severity of Illness and Risk of We to of University of Missouri for assistance with the statistical analysis. We also to for

Neurosurgery · 11 citationsread the source →

Are parenting style and controlling feeding practices related?

This study examined the relationships between parenting styles, feeding practices and BMI in a non-clinical sample of mothers and fathers of UK preschool children. Ninety-six cohabiting parents of 48 children (19 male, 29 female, mean age 42 months) completed a series of self-report questionnaires assessing parenting style, feeding practices, eating psychopathology and a range of demographic information. There were no relationships between authoritarian parenting and controlling feeding practices. In both mothers and fathers, permissive parenting style was related to lower monitoring of children's unhealthy food intake. Permissive parenting was also associated with increased use of restriction by mothers and pressure to eat by fathers. Authoritative parenting style was also related to lower use of pressure to eat by fathers only. Parenting styles were not related to child BMI in this sample. Higher child BMI was best predicted by lower paternal application of pressure to eat and greater paternal reports of drive for thinness. Parenting style may not have a direct impact on child BMI until child food selection and consumption becomes more autonomous.

Appetite · 97 citationsread the source →

Promoting school climate and health outcomes with the SEHER multi-component secondary school intervention in Bihar, India: a cluster-randomised controlled trial.

Background: School environments affect health and academic outcomes. With increasing secondary school retention in low-income and middle-income countries, promoting quality school social environments could offer a scalable opportunity to improve adolescent health and wellbeing. Methods: We did a cluster-randomised trial to assess the effectiveness of a multi-component whole-school health promotion intervention (SEHER) with integrated economic and process evaluations in grade 9 students (aged 13-14 years) at government-run secondary schools in the Nalanda district of Bihar state, India. Schools were randomly assigned (1:1:1) to three groups: the SEHER intervention delivered by a lay counsellor (the SEHER Mitra [SM] group), the SEHER intervention delivered by a teacher (teacher as SEHER Mitra [TSM] group), and a control group in which only the standard government-run classroom-based life-skills Adolescence Education Program was implemented. The primary outcome was school climate measured with the Beyond Blue School Climate Questionnaire (BBSCQ). Students were assessed at the start of the academic year (June, 2015) and again 8 months later at the end of the academic year (March, 2016) via self-completed questionnaires. This study is registered with ClinicalTrials.gov, number NCT02484014. Findings: Of the 112 eligible schools in the Nalanda district, 75 were randomly selected to participate in the trial. We randomly assigned 25 schools to each of the three groups. One school subsequently dropped out of the TSM group, leaving 24 schools in this group. The baseline survey included a total of 13 035 participants, and the endpoint survey included 14 414 participants. Participants in the SM-delivered intervention schools had substantially higher school climate scores at endpoint survey than those in the control group (BBSCQ baseline-adjusted mean difference [aMD] 7·57 [95% CI 6·11-9·03]; effect size 1·88 [95% CI 1·44-2·32], p<0·0001) and the TSM-delivered intervention (aMD 7·57 [95% CI 6·06-9·08]; effect size 1·88 [95% CI 1·43-2·34], p<0·0001). There was no effect of the TSM-delivered intervention compared with control (aMD -0·009 [95% CI -1·53 to 1·51], effect size 0·00 [95% CI -0·45 to 0·44], p=0·99). Compared with the control group, participants in the SM-delivered intervention schools had moderate to large improvements in the secondary outcomes of depression (aMD -1·23 [95% CI -1·89 to -0·57]), bullying (aMD -0·91 [95% CI -1·15 to -0·66]), violence victimisation (odds ratio [OR] 0·62 [95% CI 0·46-0·84]), violence perpetration (OR 0·68 [95% CI 0·48-0·96]), attitude towards gender equity (aMD 0·41 [95% CI 0·21-0·61]), and knowledge of reproductive and sexual health (aMD 0·29 [95% CI 0·06-0·53]). Similar results for these secondary outcomes were noted for the comparison between SM-delivered intervention schools and TSM-delivered intervention schools (depression: aMD -1·23 [95% CI -1·91 to -0·55]; bullying: aMD -0·83 [95% CI -1·08 to -0·57]; violence victimisation: OR 0·49 [95% CI 0·35-0·67]; violence perpetration: OR 0·49 [95% CI 0·34-0·71]; attitude towards gender equity: aMD 0·23 [95% CI 0·02-0·44]; and knowledge of reproductive and sexual health: aMD 0·22 [95% CI -0·02 to 0·47]). However, no effects on these secondary outcomes were observed for the TSM-delivered intervention schools compared with the control group (depression: aMD -0·03 [95% CI -0·70 to 0·65]; bullying: aMD -0·08 [95% CI -0·34 to 0·18]; violence victimisation: OR 1·27 [95% CI 0·93-1·73]; violence perpetration: OR 1·37 [95% CI 0·95-1·95]; attitude towards gender equity: aMD 0·17 [95% CI -0·09 to 0·38]; and knowledge of reproductive and sexual health: aMD 0·06 [95% CI -0·18 to 0·32]). Interpretation: The multi-component whole-school SEHER health promotion intervention had substantial beneficial effects on school climate and health-related outcomes when delivered by lay counsellors, but no effects when delivered by teachers. Future research should focus on the evaluation of the scaling up of the SEHER intervention in diverse contexts and delivery agents. Funding: John D. and Catherine T. MacArthur Foundation, USA and the United Nations Population Fund India Office.

Lancet (London, England) · randomised controlled trial · 121 citationsread the source →

Cognitive behavioural therapy for adults with dissociative seizures (CODES): a pragmatic, multicentre, randomised controlled trial.

Background: Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency. Methods: In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544. Findings: Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0-20] in the CBT plus standardised medical care group vs 7 seizures [1-35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56-1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference -0·53 [95% CI -0·97 to -0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference -4·12 [95% CI -6·35 to -1·89]; p<0·001), less overall psychological distress than the standardised medical care group on the Clinical Outcomes in Routine Evaluation-10 scale (estimated mean difference -1·65 [95% CI -2·96 to -0·35]; p=0·013), and fewer somatic symptoms on the modified Patient Health Questionnaire-15 scale (estimated mean difference -1·67 [95% CI -2·90 to -0·44]; p=0·008). Clinical improvement at 12 months was greater in the CBT plus standardised medical care group than the standardised medical care alone group as reported by patients (estimated mean difference 0·66 [95% CI 0·26 to 1·04]; p=0·001) and by clinicians (estimated mean difference 0·47 [95% CI 0·21 to 0·73]; p<0·001), and the CBT plus standardised medical care group had greater satisfaction with treatment than did the standardised medical care group (estimated mean difference 0·90 [95% CI 0·48 to 1·31]; p<0·001). No significant differences in patient-reported seizure severity (estimated mean difference -0·11 [95% CI -0·50 to 0·29]; p=0·593) or seizure freedom in the last 3 months of the study (estimated odds ratio [OR] 1·77 [95% CI 0·93 to 3·37]; p=0·083) were identified between the groups. Furthermore, no significant differences were identified in the proportion of patients who had a more than 50% reduction in dissociative seizure frequency compared with baseline (OR 1·27 [95% CI 0·80 to 2·02]; p=0·313). Additionally, the 12-item Short Form survey-version 2 scores (estimated mean difference for the Physical Component Summary score 1·78 [95% CI -0·37 to 3·92]; p=0·105; estimated mean difference for the Mental Component Summary score 2·22 [95% CI -0·30 to 4·75]; p=0·084), the Generalised Anxiety Disorder-7 scale score (estimated mean difference -1·09 [95% CI -2·27 to 0·09]; p=0·069), and the Patient Health Questionnaire-9 scale depression score (estimated mean difference -1·10 [95% CI -2·41 to 0·21]; p=0·099) did not differ significantly between groups. Changes in dissociative seizures (rated by others) could not be assessed due to insufficient data. During the 12-month period, the number of adverse events was similar between the groups: 57 (31%) of 186 participants in the CBT plus standardised medical care group reported 97 adverse events and 53 (29%) of 182 participants in the standardised medical care group reported 79 adverse events. Interpretation: CBT plus standardised medical care had no statistically significant advantage compared with standardised medical care alone for the reduction of monthly seizures. However, improvements were observed in a number of clinically relevant secondary outcomes following CBT plus standardised medical care when compared with standardised medical care alone. Thus, adults with dissociative seizures might benefit from the addition of dissociative seizure-specific CBT to specialist care from neurologists and psychiatrists. Future work is needed to identify patients who would benefit most from a dissociative seizure-specific CBT approach. Funding: National Institute for Health Research, Health Technology Assessment programme.

The lancet. Psychiatry · randomised controlled trial · 192 citationsread the source →

Sphincter of Oddi botulinum toxin injection to prevent pancreatic fistula after distal pancreatectomy.

Background: Postoperative pancreatic fistula represents the most important complication after distal pancreatectomy. The aim of this study was to evaluate the use of a preoperative endoscopic injection of botulinum toxin into the sphincter of Oddi to prevent postoperative pancreatic fistula (German Clinical Trials Register number: DRKS00007885). Methods: This was an investigator-initiated, prospective clinical phase I/II trial with an exploratory study design. We included patients who underwent preoperative endoscopic sphincter botulinum toxin injection (100 units of Botox). End points were the feasibility, safety, and postoperative outcomes, including postoperative pancreatic fistula within 30 days after distal pancreatectomy. Botulinum toxin patients were compared with a control collective of patients undergoing distal pancreatectomy without botulinum toxin injection by case-control matching in a 1:1 ratio. Results: Between February 2015 and February 2016, 29 patients were included. All patients underwent successful sphincter of Oddi botulinum toxin injection within a median of 6 (range 0-10) days before operation. One patient had an asymptomatic, self-limiting (48 hours) increase in serum amylase and lipase after injection. Distal pancreatectomy was performed in 24/29 patients; 5 patients were not resectable. Of the patients receiving botulinum toxin, 7 (29%) had increased amylase levels in drainage fluid on postoperative day 3 (the International Study Group of Pancreatic Surgery definition of postoperative pancreatic fistula grade A) without symptoms or need for reintervention. Importantly, no clinically relevant fistulas (International Study Group of Pancreatic Surgery grades B/C) were observed in botulinum toxin patients compared to 33% postoperative pancreatic fistula grade B/C in case-control patients (P < .004). Conclusion: Preoperative sphincter of Oddi botulinum toxin injection is a novel and safe approach to decrease the incidence of clinically relevant postoperative pancreatic fistula after distal pancreatectomy. The results of the present trial suggest its efficacy in the prevention of clinically relevant postoperative pancreatic fistula and are validated currently in the German Federal Government-sponsored, multicenter, randomized controlled PREBOT trial.

Surgery · randomised controlled trial · 44 citationsread the source →

Uptake of antiretroviral therapy and male circumcision after community-based HIV testing and strategies for linkage to care versus standard clinic referral: a multisite, open-label, randomised controlled trial in South Africa and Uganda.

Background: Male circumcision decreases HIV acquisition by 60%, and antiretroviral therapy (ART) almost eliminates HIV transmission from HIV-positive people who are virally suppressed; however, coverage of these interventions has lagged behind targets. We aimed to assess whether community-based HIV testing with counsellor support and point-of-care CD4 cell count testing would increase uptake of ART and male circumcision. Methods: We did this multisite, open-label, randomised controlled trial in six research-naive communities in rural South Africa and Uganda. Eligible HIV-positive participants (aged ≥16 years) were randomly assigned (1:1:1) in a factorial design to receive lay counsellor clinic linkage facilitation, lay counsellor follow-up home visits, or standard-of-care clinic referral, and then (1:1) either point-of-care CD4 cell count testing or referral for CD4 testing. HIV-negative uncircumcised men (aged 16-49 years) who could receive secure mobile phone text messages were randomly assigned (1:1:1) to receive text message reminders, lay counsellor visits, or standard clinic referral. The study biostatistician generated the randomisation schedule via a computer-generated random number program with varying block sizes (multiples of six or three) stratified by country. Primary outcomes for HIV-positive people were obtaining a CD4 cell count, linkage to an HIV clinic, ART initiation, and viral suppression at 9 months, and for HIV-negative uncircumcised men were visiting a circumcision facility and uptake of male circumcision at 3 months. We assessed social harms as a safety outcome throughout the study. We did the primary analyses by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02038582. Findings: Between June 6, 2013, and March 11, 2015, 15 332 participants were tested. 2339 (15%) participants tested HIV positive, of whom 1325 (57%) were randomly assigned to receive lay counsellor clinic linkage facilitation (n=437), lay counsellor follow-up home visits (n=449), or standard clinic referral (n=439), and then point-of-care CD4 cell testing (n=206, n=220, and n=213, respectively) or referral for CD4 testing (n=231, n=229, and n=226, respectively). 12 993 (85%) participants tested HIV negative, of whom 750 (6%) uncircumcised men were randomly assigned to receive clinic referral (n=230), text message reminders (n=288), or lay counsellor follow-up visits (n=232). 1218 (93%) of 1303 HIV-positive participants were linked to care, but only 488 (37%) participants initiated ART. Overall, 635 (50%) of 1272 HIV-positive individuals achieved viral suppression at 9 months: 219 (52%) of 419 participants in the clinic facilitation group, 202 (47%) of 431 participants in the lay counsellor follow-up group, and 214 (51%) of 422 participants in the clinic referral group, with no significant differences between groups (p=0·668 for clinic facilitation and p=0·273 for lay counsellor follow-up vs clinic referral). 523 (72%) of 734 HIV-negative men visited a circumcision facility, with no difference between groups. 62 (28%) of 224 men were circumcised in the male circumcision clinic referral group compared with 137 (48%) of 284 men in the text message reminder group (relative risk 1·72, 95% CI 1·36-2·17; p<0·0001) and 106 (47%) of 226 men in the lay counsellor follow-up group (1·67, 1·29-2·14; p=0·0001). No cases of study-related social harm were reported, including probing about partnership separation, unintended disclosure, gender-based violence, and stigma. Interpretation: All the community-based strategies achieved high rates of linkage of HIV-positive people to HIV clinics, roughly a third of whom initiated ART, and of those more than 80% were virally suppressed at 9 months. Uptake of male circumcision was almost two-times higher in men who received text message reminders or lay counsellor visits than in those who received standard-of-care clinic referral. Clinic barriers to ART initiation should be addressed in future strategies to increase the proportion of HIV-positive people accessing treatment and achieving viral suppression. Funding: National Institute of Allergy and Infectious Diseases, National Institutes of Health.

The lancet. HIV · randomised controlled trial · 65 citationsread the source →

Dialectical behavior therapy for high suicide risk in individuals with borderline personality disorder: a randomized clinical trial and component analysis.

Importance: Dialectical behavior therapy (DBT) is an empirically supported treatment for suicidal individuals. However, DBT consists of multiple components, including individual therapy, skills training, telephone coaching, and a therapist consultation team, and little is known about which components are needed to achieve positive outcomes. Objective: To evaluate the importance of the skills training component of DBT by comparing skills training plus case management (DBT-S), DBT individual therapy plus activities group (DBT-I), and standard DBT which includes skills training and individual therapy. Design, setting, and participants: We performed a single-blind randomized clinical trial from April 24, 2004, through January 26, 2010, involving 1 year of treatment and 1 year of follow-up. Participants included 99 women (mean age, 30.3 years; 69 [71%] white) with borderline personality disorder who had at least 2 suicide attempts and/or nonsuicidal self-injury (NSSI) acts in the last 5 years, an NSSI act or suicide attempt in the 8 weeks before screening, and a suicide attempt in the past year. We used an adaptive randomization procedure to assign participants to each condition. Treatment was delivered from June 3, 2004, through September 29, 2008, in a university-affiliated clinic and community settings by therapists or case managers. Outcomes were evaluated quarterly by blinded assessors. We hypothesized that standard DBT would outperform DBT-S and DBT-I. Interventions: The study compared standard DBT, DBT-S, and DBT-I. Treatment dose was controlled across conditions, and all treatment providers used the DBT suicide risk assessment and management protocol. Main outcomes and measures: Frequency and severity of suicide attempts and NSSI episodes. Results: All treatment conditions resulted in similar improvements in the frequency and severity of suicide attempts, suicide ideation, use of crisis services due to suicidality, and reasons for living. Compared with the DBT-I group, interventions that included skills training resulted in greater improvements in the frequency of NSSI acts (F1,85 = 59.1 [P < .001] for standard DBT and F1,85 = 56.3 [P < .001] for DBT-S) and depression (t399 = 1.8 [P = .03] for standard DBT and t399 = 2.9 [P = .004] for DBT-S) during the treatment year. In addition, anxiety significantly improved during the treatment year in standard DBT (t94 = -3.5 [P < .001]) and DBT-S (t94 = -2.6 [P = .01]), but not in DBT-I. Compared with the DBT-I group, the standard DBT group had lower dropout rates from treatment (8 patients [24%] vs 16 patients [48%] [P = .04]), and patients were less likely to use crisis services in follow-up (ED visits, 1 [3%] vs 3 [13%] [P = .02]; psychiatric hospitalizations, 1 [3%] vs 3 [13%] [P = .03]). Conclusions and relevance: A variety of DBT interventions with therapists trained in the DBT suicide risk assessment and management protocol are effective for reducing suicide attempts and NSSI episodes. Interventions that include DBT skills training are more effective than DBT without skills training, and standard DBT may be superior in some areas. Trial registration: clinicaltrials.gov Identifier: NCT00183651.

JAMA psychiatry · randomised controlled trial · 325 citationsread the source →

A novel digital intervention for actively reducing severity of paediatric ADHD (STARS-ADHD): a randomised controlled trial.

Background: Attention-deficit hyperactivity disorder (ADHD) is a common paediatric neurodevelopmental disorder with substantial effect on families and society. Alternatives to traditional care, including novel digital therapeutics, have shown promise to remediate cognitive deficits associated with this disorder and may address barriers to standard therapies, such as pharmacological interventions and behavioural therapy. AKL-T01 is an investigational digital therapeutic designed to target attention and cognitive control delivered through a video game-like interface via at-home play for 25 min per day, 5 days per week for 4 weeks. This study aimed to assess whether AKL-T01 improved attentional performance in paediatric patients with ADHD. Methods: The Software Treatment for Actively Reducing Severity of ADHD (STARS-ADHD) was a randomised, double-blind, parallel-group, controlled trial of paediatric patients (aged 8-12 years, without disorder-related medications) with confirmed ADHD and Test of Variables of Attention (TOVA) Attention Performance Index (API) scores of -1·8 and below done by 20 research institutions in the USA. Patients were randomly assigned 1:1 to AKL-T01 or a digital control intervention. The primary outcome was mean change in TOVA API from pre-intervention to post-intervention. Safety, tolerability, and compliance were also assessed. Analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02674633 and is completed. Findings: Between July 15, 2016, and Nov 30, 2017, 857 patients were evaluated and 348 were randomly assigned to receive AKL-T01 or control. Among patients who received AKL-T01 (n=180 [52%]; mean [SD] age, 9·7 [1·3] years) or control (n=168 [48%]; mean [SD] age, 9·6 [1·3] years), the non-parametric estimate of the population median change from baseline TOVA API was 0·88 (95% CI 0·24-1·49; p=0·0060). The mean (SD) change from baseline on the TOVA API was 0·93 (3·15) in the AKL-T01 group and 0·03 (3·16) in the control group. There were no serious adverse events or discontinuations. Treatment-related adverse events were mild and included frustration (5 [3%] of 180) and headache (3 [2%] of 180). Patient compliance was a mean of 83 (83%) of 100 expected sessions played (SD, 29·2 sessions). Interpretation: Although future research is needed for this digital intervention, this study provides evidence that AKL-T01 might be used to improve objectively measured inattention in paediatric patients with ADHD, while presenting minimal adverse events. Funding: Sponsored by Akili Interactive Labs.

The Lancet. Digital health · randomised controlled trial · 215 citationsread the source →

Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial.

Background: The antiviral efficacy of remdesivir against SARS-CoV-2 is still controversial. We aimed to evaluate the clinical efficacy of remdesivir plus standard of care compared with standard of care alone in patients admitted to hospital with COVID-19, with indication of oxygen or ventilator support. Methods: DisCoVeRy was a phase 3, open-label, adaptive, multicentre, randomised, controlled trial conducted in 48 sites in Europe (France, Belgium, Austria, Portugal, Luxembourg). Adult patients (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and illness of any duration were eligible if they had clinical evidence of hypoxaemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzymes, severe chronic kidney disease, any contraindication to one of the studied treatments or their use in the 29 days before random assignment, or use of ribavirin, as well as pregnancy or breastfeeding. Participants were randomly assigned (1:1:1:1:1) to receive standard of care alone or in combination with remdesivir, lopinavir-ritonavir, lopinavir-ritonavir and interferon beta-1a, or hydroxychloroquine. Randomisation used computer-generated blocks of various sizes; it was stratified on severity of disease at inclusion and on European administrative region. Remdesivir was administered as 200 mg intravenous infusion on day 1, followed by once daily, 1-h infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. The primary outcome was the clinical status at day 15 measured by the WHO seven-point ordinal scale, assessed in the intention-to-treat population. Safety was assessed in the modified intention-to-treat population and was one of the secondary outcomes. This trial is registered with the European Clinical Trials Database, EudraCT2020-000936-23, and ClinicalTrials.gov, NCT04315948. Findings: Between March 22, 2020, and Jan 21, 2021, 857 participants were enrolled and randomly assigned to remdesivir plus standard of care (n=429) or standard of care only (n=428). 15 participants were excluded from analysis in the remdesivir group, and ten in the control group. At day 15, the distribution of the WHO ordinal scale was: (1) not hospitalised, no limitations on activities (61 [15%] of 414 in the remdesivir group vs 73 [17%] of 418 in the control group); (2) not hospitalised, limitation on activities (129 [31%] vs 132 [32%]); (3) hospitalised, not requiring supplemental oxygen (50 [12%] vs 29 [7%]); (4) hospitalised, requiring supplemental oxygen (76 [18%] vs 67 [16%]); (5) hospitalised, on non-invasive ventilation or high flow oxygen devices (15 [4%] vs 14 [3%]); (6) hospitalised, on invasive mechanical ventilation or extracorporeal membrane oxygenation (62 [15%] vs 79 [19%]); (7) death (21 [5%] vs 24 [6%]). The difference between treatment groups was not significant (odds ratio 0·98 [95% CI 0·77-1·25]; p=0·85). There was no significant difference in the occurrence of serious adverse events between treatment groups (remdesivir, 135 [33%] of 406 vs control, 130 [31%] of 418; p=0·48). Three deaths (acute respiratory distress syndrome, bacterial infection, and hepatorenal syndrome) were considered related to remdesivir by the investigators, but only one by the sponsor's safety team (hepatorenal syndrome). Interpretation: No clinical benefit was observed from the use of remdesivir in patients who were admitted to hospital for COVID-19, were symptomatic for more than 7 days, and required oxygen support. Funding: European Union Commission, French Ministry of Health, Domaine d'intérêt majeur One Health Île-de-France, REACTing, Fonds Erasme-COVID-Université Libre de Bruxelles, Belgian Health Care Knowledge Centre, Austrian Group Medical Tumor, European Regional Development Fund, Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation. Translation: For the French translation of the abstract see Supplementary Materials section.

The Lancet. Infectious diseases · randomised controlled trial · 264 citationsread the source →

Physicians' needs in coping with emotional stressors: the case for peer support.

Objective: To design an evidence-based intervention to address physician distress, based on the attitudes toward support among physicians at our hospital. Design, setting, and participants: A 56-item survey was administered to a convenience sample (n = 108) of resident and attending physicians at surgery, emergency medicine, and anesthesiology departmental conferences at a large tertiary care academic hospital. Main outcome measures: Likelihood of seeking support, perceived barriers, awareness of available services, sources of support, and experience with stress. Results: Among the resident and attending physicians, 79% experienced either a serious adverse patient event and/or a traumatic personal event within the preceding year. Willingness to seek support was reported for legal situations (72%), involvement in medical errors (67%), adverse patient events (63%), substance abuse (67%), physical illness (62%), mental illness (50%), and interpersonal conflict at work (50%). Barriers included lack of time (89%), uncertainty or difficulty with access (69%), concerns about lack of confidentiality (68%), negative impact on career (68%), and stigma (62%). Physician colleagues were the most popular potential sources of support (88%), outnumbering traditional mechanisms such as the employee assistance program (29%) and mental health professionals (48%). Based on these results, a one-on-one peer physician support program was incorporated into support services at our hospital. Conclusions: Despite the prevalence of stressful experiences and the desire for support among physicians, established services are underused. As colleagues are the most acceptable sources of support, we advocate peer support as the most effective way to address this sensitive but important issue.

Archives of surgery (Chicago, Ill. : 1960) · 181 citationsread the source →

The Social Epidemiology of Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome

Social epidemiology is defined as the study of the distribution of health outcomes and their social determinants (1). It builds on the classic epidemiologic triangle of host, agent, and environment to focus explicitly on the role of social determinants in infectious disease transmission and progression. These determinants are the “features of and pathways by which societal conditions affect health” (2, p. 697). Early studies of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) focused on individual characteristics and behaviors in determining HIV risk, an approach that Fee and Krieger (3) refer to as “biomedical individualism.” Biomedical individualism is the basis of risk factor epidemiology; by contrast, the social epidemiology perspective emphasizes social conditions as fundamental causes of disease (4) (table 1). Social epidemiologists examine how persons become exposed to risk or protective factors and under what social conditions individual risk factors are related to disease. Social factors are thus the focus of analysis and are not simply adjusted for as potentially confounding factors or used as proxies for unavailable individual-level data. Social factors are indeed critical to understanding nonuniform infectious disease patterns that emerge as a result of the dependent nature of disease transmission or the idea that an outcome in one person is dependent upon outcomes and exposures in others (5, 6). Contact patterns that enhance HIV/AIDS vulnerability may be conceptualized at multiple levels. Figure 1 distinguishes determinants of HIV/AIDS at three levels: individual, social, and structural. Individual factors include biologic, demographic, and behavioral risk factors that may influence the risk of HIV acquisition and disease progression. Social-level factors include critical pathways by which community and network structures link persons to society. These structures are central to understanding the diffusion and differential distribution of HIV/AIDS in population subgroups. Structural-level factors include social and economic factors, as well as laws and policies. These factors, in turn, affect HIV transmission dynamics and the differential distribution of HIV/AIDS. Infectious disease epidemiology provides models of the mechanisms through which social determinants affect HIV transmission (7). For example, the basic reproductive number of an infectious disease, R0 (8), describes secondary infections that arise from a primary infection. In the equation R0 = βCD, β is the probability of infection per contact, C is the number of contacts, and D is the duration of infectivity. The goal of intervention efforts is to reduce the empirical value of these terms by modifying the social conditions under which individual risk factors lead to disease. Examples of factors that affect the component terms of R0 in HIV epidemiology are presented in table 2. In this review, we present existing evidence linking social and structural determinants to HIV/AIDS. In addition, we discuss the implications of these findings for future social epidemiology research on HIV/AIDS as well as the design of more effective HIV/AIDS interventions. We searched the published literature to identify conceptual and empirical research reports on the social epidemiology of HIV/AIDS. Five databases were searched: PsycINFO (American Psychological Association, Washington, DC), PubMed (MEDLINE; National Institutes of Health, Bethesda, Maryland), Social Science Citation Index (Web of Science; Thomson ISI, Stamford, Connecticut), Sociological Abstracts (CSA, Bethesda, Maryland), and Digital Dissertations (ProQuest; UMI, Ann Arbor, Michigan). Searches were designed to include the factors we specified in our framework as social or structural factors (figure 1). Searches were limited to published articles in the English language for the period 1981–2003. The following keywords were included in each search: AIDS/acquired immunodeficiency syndrome, HIV, and epidemiol*. Additional searches were conducted by using combinations of keywords listed in Appendix table 1 corresponding with our framework. We identified four categories of social-level factors of importance to HIV/AIDS epidemiology: cultural context, social networks, neighborhood effects, and social capital. Each uses different conceptual and methodological approaches to examine the effects of social forces on population HIV/AIDS vulnerability. Anthropologist Edward Tylor defined culture as “that complex whole which includes knowledge, belief, art, law, morals, custom, and any other capabilities and habits acquired by man as a member of society” (9, p. 1). Anthropologic and epidemiologic approaches may be integrated in a variety of ways to identify features of the social environment that affect HIV/AIDS risk. One way to explore how the social environment affects HIV/AIDS epidemiology is through the use of mixed research methods. Mixed-methods study designs integrate qualitative and quantitative research methods either sequentially or concurrently (10). In sequential study designs, qualitative methods may be used to explore a topic under study or to explain quantitative epidemiologic findings. Concurrent study designs are meant to confirm, cross-validate, or corroborate findings within a single study. A common type of concurrent mixed methods study is “triangulation,” and this approach has been used extensively in rapid assessments of illicit drug use and HIV/AIDS (11–13). Mixed methods approaches are particularly well suited to the investigation of the often hidden and stigmatizing behavioral and social factors underlying HIV epidemics. One exemplary study combining qualitative methods with quantitative methods was conducted by Beyrer et al. (14) to examine the role of overland heroin trafficking routes in shaping explosive HIV/AIDS epidemics among injection drug users in Southeast Asia. Piecing together data from a variety of sources, including existing epidemiologic data, key informant interviews, and laboratory data, this study revealed that distinct HIV subtypes emerged and recombined along drug trafficking routes originating in Myanmar, one of the world’s largest heroin producers. Along these trafficking routes, communities of injection drug users formed, facilitating the spread of HIV into local communities in Laos, Thailand, Vietnam, India, and China (refer, for example, to Panda et al. (15)). This illustration highlights the broader understanding of HIV/AIDS epidemiology that can be achieved by examining the interplay between contextual factors and social and behavioral factors. Investigation of social networks in HIV/AIDS began with the mapping of relationships between one of the first identified AIDS cases, an airline steward, and a large number of his male sex partners in the early 1980s (16). Social network analysis generates measures of the quality, density, position, and structure of relationships between persons, including dyads (partnerships), personal networks (“egocentric” networks), and larger communities (“sociometric” networks) (17, 18). Social networks can influence health outcomes in direct and indirect ways, including 1) social influence, 2) social engagement and participation, 3) prevalence of infectious disease and network member mixing, 4) access to material goods and informational resources, and 5) social support (19). Researchers have demonstrated that patterns in the structure of relationships—rather than differences in individual risk behaviors alone—explain observed HIV patterns (20, 21). The theoretical foundation for examining social networks in HIV research is closely tied to advances in sexually transmitted disease (STD) epidemiology. A key concept from STD epidemiology is the notion of the “core group,” a small group of disease transmitters responsible for a large proportion of cases (22). Friedman et al. (23) found that individuals’ locations within sociometric risk networks were associated with HIV risk among a group of injection drug users in New York City. Other concepts from STD epidemiology, such as partner concurrency, bridging, and mixing patterns, are also important in understanding HIV risk (24–29). Specific network characteristics that have been associated with HIV/AIDS include the size of subgroups and their distribution in a network (23), the centrality of HIV-positive persons within networks (30), partner selection patterns (24, 31–33), and concurrent sexual partnerships (28). Inclusion of these variables has been shown to improve transmission estimates in mathematical modeling (34, 35). Social and normative influences have also been associated with individual HIV risks (36, 37). Network-related social and normative influences are predictive of illicit drug use (38) and condom use behavior (37, 39), highlighting the importance of network-based interventions for HIV prevention (18). Kelly et al. (40, 41) developed a popular opinion leader model that has been effective in reducing HIV risk in several populations, including men who have sex with men and women in low-income housing (42). The success of this model has led to its adaption for international use by the National Institute of Mental Health Collaborative HIV/STD Prevention Trial in China, India, Peru, Russia, and Zimbabwe. Neighborhoods represent the intersection of social networks and physical spatial locations, a confluence Wallace (43) has called the “sociogeographic networks” through which infectious diseases spread. Early interest in the role of neighborhood social environment in disease transmission was sparked by a study in Colorado Springs, Colorado, in which researchers found that gonorrhea was highly focused geographically in core residential neighborhoods (44). Both direct and indirect mechanisms may determine how neighborhood-level factors shape population HIV/AIDS patterns. Direct mechanisms are those that increase the likelihood of a person coming into contact with someone who is HIV positive, for example, through residential segregation and the social isolation of marginalized populations. Indirect mechanisms include those that increase population vulnerability to HIV/AIDS, such as exposure to poor socioeconomic conditions, high unemployment, or the proliferation of illicit drug markets. A range of neighborhood-level factors have been examined in relation to infectious disease, including poverty and income (45, 46), residential segregation (47), and neighborhood physical environment (48, 49). Current research in neighborhood and area effects on health emphasizes the importance of moving beyond documentation of associations to analyze the social and epidemiologic mechanisms through which neighborhood effects might operate (50–54). Increasing concentrations of affluence and poverty are contributing to what demographer Douglas Massey has called “a radical change in the geographic basis of human society” (55, p. 395). Powerful social and economic forces in US cities are increasing neighborhood segregation by class and race/ethnicity (56, 57). Resulting social disorganization and loss of resources and services in poor neighborhoods are in turn shaping HIV/AIDS patterns at the neighborhood level. In a number of studies in New York City, for example, Wallace (58–63) has examined the complex interplay of public policies such as “planned shrinkage” with HIV epidemic dynamics in the Bronx, documenting the “synergy of plagues” that has accompanied rapid social change and the destruction of essential protective networks in poor communities. Using AIDS surveillance data, ecologic studies conducted in various US cities have also consistently found significant associations between income and poverty measures and neighborhood-level AIDS incidence and prevalence rates, and these findings have been consistent across census block groups (46), census tracts (64), and zip codes (65, 66). 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Epidemiologic Reviews · meta-analysis · 394 citationsread the source →

A Randomized Trial of MBSR Versus Aerobic Exercise for Social Anxiety Disorder

OBJECTIVE: Effective treatments for social anxiety disorder (SAD) exist, but additional treatment options are needed for nonresponders as well as those who are either unable or unwilling to engage in traditional treatments. Mindfulness-based stress reduction (MBSR) is one nontraditional treatment that has demonstrated efficacy in treating other mood and anxiety disorders, and preliminary data suggest its efficacy in SAD as well. METHOD: Fifty-six adults (52% female; 41% Caucasian; age mean [M] ± standard deviation [SD]: 32.8 ± 8.4) with SAD were randomized to MBSR or an active comparison condition, aerobic exercise (AE). At baseline and post-intervention, participants completed measures of clinical symptoms (Liebowitz Social Anxiety Scale, Social Interaction Anxiety Scale, Beck Depression Inventory-II, and Perceived Stress Scale) and subjective well-being (Rosenberg Self-Esteem Scale, Satisfaction with Life Scale, Self-Compassion Scale, and UCLA-8 Loneliness Scale). At 3 months post-intervention, a subset of these measures was readministered. For clinical significance analyses, 48 healthy adults (52.1% female; 56.3% Caucasian; age [M ± SD]: 33.9 ± 9.8) were recruited. MBSR and AE participants were also compared with a separate untreated group of 29 adults (44.8% female; 48.3% Caucasian; age [M ± SD]: 32.3 ± 9.4) with generalized SAD who completed assessments over a comparable time period with no intervening treatment. RESULTS: A 2 (Group) x 2 (Time) repeated measures analyses of variance (ANOVAs) on measures of clinical symptoms and well-being were conducted to examine pre-intervention to post-intervention and pre-intervention to 3-month follow-up. Both MBSR and AE were associated with reductions in social anxiety and depression and increases in subjective well-being, both immediately post-intervention and at 3 months post-intervention. When participants in the randomized controlled trial were compared with the untreated SAD group, participants in both interventions exhibited improvements on measures of clinical symptoms and well-being. CONCLUSION: Nontraditional interventions such as MBSR and AE merit further exploration as alternative or complementary treatments for SAD.

Journal of Clinical Psychology · randomised controlled trial · 214 citationsread the source →

Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial.

Background: Obesity is associated with a reduction in life expectancy and an increase in mortality from cardiovascular diseases, cancer, and other causes. We therefore assessed the efficacy and safety of two doses of phentermine plus topiramate controlled-release combination as an adjunct to diet and lifestyle modification for weight loss and metabolic risk reduction in individuals who were overweight and obese, with two or more risk factors. Methods: In this 56-week phase 3 trial, we randomly assigned overweight or obese adults (aged 18-70 years), with a body-mass index of 27-45 kg/m(2) and two or more comorbidities (hypertension, dyslipidaemia, diabetes or prediabetes, or abdominal obesity) to placebo, once-daily phentermine 7·5 mg plus topiramate 46·0 mg, or once-daily phentermine 15·0 mg plus topiramate 92·0 mg in a 2:1:2 ratio in 93 centres in the USA. Drugs were administered orally. Patients were randomly assigned by use of a computer-generated algorithm that was implemented through an interactive voice response system, and were stratified by sex and diabetic status. Investigators, patients, and study sponsors were masked to treatment. Primary endpoints were the percentage change in bodyweight and the proportion of patients achieving at least 5% weight loss. Analysis was by intention to treat. This study is registered with Clinical Trials.gov, number NCT00553787. Findings: Of 2487 patients, 994 were assigned to placebo, 498 to phentermine 7·5 mg plus topiramate 46·0 mg, and 995 to phentermine 15·0 mg plus topiramate 92·0 mg; 979, 488, and 981 patients, respectively, were analysed. At 56 weeks, change in bodyweight was -1·4 kg (least-squares mean -1·2%, 95% CI -1·8 to -0·7), -8·1 kg (-7·8%, -8·5 to -7·1; p<0·0001), and -10·2 kg (-9·8%, -10·4 to -9·3; p<0·0001) in the patients assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus topiramate 92·0 mg, respectively. 204 (21%) patients achieved at least 5% weight loss with placebo, 303 (62%; odds ratio 6·3, 95% CI 4·9 to 8·0; p<0·0001) with phentermine 7·5 mg plus topiramate 46·0 mg, and 687 (70%; 9·0, 7·3 to 11·1; p<0·0001) with phentermine 15·0 mg plus topiramate 92·0 mg; for ≥10% weight loss, the corresponding numbers were 72 (7%), 182 (37%; 7·6, 5·6 to 10·2; p<0·0001), and 467 (48%; 11·7, 8·9 to 15·4; p<0·0001). The most common adverse events were dry mouth (24 [2%], 67 [13%], and 207 [21%] in the groups assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus topiramate 92·0 mg, respectively), paraesthesia (20 [2%], 68 [14%], and 204 [21%], respectively), constipation (59 [6%], 75 [15%], and 173 [17%], respectively), insomnia (47 [5%], 29 [6%], and 102 [10%], respectively), dizziness (31 [3%], 36 [7%], 99 [10%], respectively), and dysgeusia (11 [1%], 37 [7%], and 103 [10%], respectively). 38 (4%) patients assigned to placebo, 19 (4%) to phentermine 7·5 mg plus topiramate 46·0 mg, and 73 (7%) to phentermine 15·0 mg plus topiramate 92·0 mg had depression-related adverse events; and 28 (3%), 24 (5%), and 77 (8%), respectively, had anxiety-related adverse events. Interpretation: The combination of phentermine and topiramate, with office-based lifestyle interventions, might be a valuable treatment for obesity that can be provided by family doctors. Funding: Vivus.

Lancet (London, England) · randomised controlled trial · 667 citationsread the source →

The epidemiology of trauma and post-traumatic stress disorder in a representative cohort of young people in England and Wales.

Background: Despite the emphasis placed on childhood trauma in psychiatry, comparatively little is known about the epidemiology of trauma and trauma-related psychopathology in young people. We therefore aimed to evaluate the prevalence, clinical features, and risk factors associated with trauma exposure and post-traumatic stress disorder (PTSD) in young people. Methods: We carried out a comprehensive epidemiological study based on participants from the Environmental Risk Longitudinal Twin Study, a population-representative birth-cohort of 2232 children born in England and Wales in 1994-95. At the follow-up home visit at age 18 years, participants were assessed with structured interviews for trauma exposure, PTSD, other psychopathology, risk events, functional impairment, and service use. Risk factors for PTSD were measured prospectively over four previous assessments between age 5 and 12 years. The key outcomes were the prevalence, clinical features, and risk factors associated with trauma exposure and PTSD. We also derived and tested the internal validity of a PTSD risk calculator. Findings: We found that 642 (31·1%) of 2064 participants reported trauma exposure and 160 (7·8%) of 2063 experienced PTSD by age 18 years. Trauma-exposed participants had high rates of psychopathology (187 [29·2%] of 641 for major depressive episode, 146 [22·9%] of 638 for conduct disorder, and 102 [15·9%] of 641 for alcohol dependence), risk events (160 [25·0%] of 641 for self-harm, 53 [8·3%] of 640 for suicide attempt, and 42 [6·6%] of 640 for violent offence), and functional impairment. Participants with lifetime PTSD had even higher rates of psychopathology (87 [54·7%] of 159 for major depressive episode, 43 [27·0%] of 159 for conduct disorder, and 41 [25·6%] of 160 for alcohol dependence), risk events (78 [48·8%] of 160 for self-harm, 32 [20·1%] of 159 for suicide attempt, and 19 [11·9%] of 159 for violent offence), and functional impairment. However, only 33 (20·6%) of 160 participants with PTSD received help from mental health professionals. The PTSD risk calculator had an internally validated area under the receiver operating characteristic curve of 0·74, indicating adequate discrimination of trauma-exposed participants with and without PTSD, and internally validated calibration-in-the-large of -0·10 and calibration slope of 0·90, indicating adequate calibration. Interpretation: Trauma exposure and PTSD are associated with complex psychiatric presentations, high risk, and significant impairment in young people. Improved screening, reduced barriers to care provision, and comprehensive clinical assessment are needed to ensure that trauma-exposed young people and those with PTSD receive appropriate treatment. Funding: The Medical Research Council, the National Institute of Child Health and Development, the Jacobs Foundation, the Nuffield Foundation, the National Society for Prevention of Cruelty to Children, the Economic and Social Research Council, the National Institute for Health Research, MQ, and Canadian Institutes for Advanced Research.

The lancet. Psychiatry · cohort or longitudinal · 287 citationsread the source →

The Surgeon as the Second Victim? Results of the Boston Intraoperative Adverse Events Surgeons' Attitude (BISA) Study.

Background: An intraoperative adverse event (iAE) is often directly attributable to the surgeon's technical error and/or suboptimal intraoperative judgment. We aimed to examine the psychological impact of iAEs on surgeons as well as the surgeons' attitude about iAE reporting. Study design: We conducted a web-based cross-sectional survey of all surgeons at 3 major teaching hospitals of the same university. The 29-item questionnaire was developed using a systematic closed and open approach focused on assessing the surgeons' personal account of iAE incidence, emotional response to iAEs, available support systems, and perspective about the barriers to iAE reporting. Results: The response rate was 44.8% (n = 126). Mean age of respondents was 49 years, 77% were male, and 83% performed >150 procedures/year. During the last year, 32% recalled 1 iAE, 39% recalled 2 to 5 iAEs, and 9% recalled >6 iAEs. The emotional toll of iAEs was significant, with 84% of respondents reporting a combination of anxiety (66%), guilt (60%), sadness (52%), shame/embarrassment (42%), and anger (29%). Colleagues constituted the most helpful support system (42%) rather than friends or family; a few surgeons needed psychological therapy/counseling. As for reporting, 26% preferred not to see their individual iAE rates, and 38% wanted it reported in comparison with their aggregate colleagues' rate. The most common barriers to reporting iAEs were fear of litigation (50%), lack of a standardized reporting system (49%), and absence of a clear iAE definition (48%). Conclusions: Intraoperative AEs occur often, have a significant negative impact on surgeons' well-being, and barriers to transparency are fear of litigation and absence of a well-defined reporting system. Efforts should be made to support surgeons and standardize reporting when iAEs occur.

Journal of the American College of Surgeons · cohort or longitudinal · 110 citationsread the source →

Modifiable risk factors in the first 1000 days for subsequent risk of childhood overweight in an Asian cohort: significance of parental overweight status.

Background/objective: Many studies have identified early-life risk factors for subsequent childhood overweight/obesity, but few have evaluated how they combine to influence risk of childhood overweight/obesity. We examined associations, individually and in combination, of potentially modifiable risk factors in the first 1000 days after conception with childhood adiposity and risk of overweight/obesity in an Asian cohort. Methods: Six risk factors were examined: maternal pre-pregnancy overweight/obesity (body mass index (BMI) ⩾25 kg m-2), paternal overweight/obesity at 24 months post delivery, maternal excessive gestational weight gain, raised maternal fasting glucose during pregnancy (⩾5.1 mmol l-1), breastfeeding duration <4 months and early introduction of solid foods (<4 months). Associations between number of risk factors and adiposity measures (BMI, waist-to-height ratio (WHtR), sum of skinfolds (SSFs), fat mass index (FMI) and overweight/obesity) at 48 months were assessed using multivariable regression models. Results: Of 858 children followed up at 48 months, 172 (19%) had none, 274 (32%) had 1, 244 (29%) had 2, 126 (15%) had 3 and 42 (5%) had ⩾4 risk factors. Adjusting for confounders, significant graded positive associations were observed between number of risk factors and adiposity outcomes at 48 months. Compared with children with no risk factors, those with four or more risk factors had s.d. unit increases of 0.78 (95% confidence interval 0.41-1.15) for BMI, 0.79 (0.41-1.16) for WHtR, 0.46 (0.06-0.83) for SSF and 0.67 (0.07-1.27) for FMI. The adjusted relative risk of overweight/obesity in children with four or more risk factors was 11.1(2.5-49.1) compared with children with no risk factors. Children exposed to maternal pre-pregnancy (11.8(9.8-13.8)%) or paternal overweight status (10.6(9.6-11.6)%) had the largest individual predicted probability of child overweight/obesity. Conclusions: Early-life risk factors added cumulatively to increase childhood adiposity and risk of overweight/obesity. Early-life and preconception intervention programmes may be more effective in preventing overweight/obesity if they concurrently address these multiple modifiable risk factors.

International journal of obesity (2005) · 47 citationsread the source →

Heart rate variability

IN FOCUSHeart rate variabilityHarald M. StaussHarald M. StaussDepartment of Exercise Science, University of Iowa, Iowa City, Iowa 52242Published Online:01 Nov 2003https://doi.org/10.1152/ajpregu.00452.2003MoreSectionsPDF (59 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations the rhythm of the heart has not only fascinated cardiologists but also inspired poets and musicians. Indeed, the periodic beat of the heart was used to define the speed of music. In music notation, the traditional Italian term "moderato" originally referred to one beat of the measure per walking pace (76-80 paces/min) or heartbeat (∼72 beats/min). The use of the heartbeat to define the speed of music may imply that the periodicity of the beat of the heart is very constant. However, this is not necessarily the case. In fact, loss of heart rate variability can indicate severe cardiovascular diseases and reliably predict poor outcome of such conditions (18, 22, 27, 47a). This In Focus article reviews sources of heart rate variability, its role as a prognostic marker for cardiovascular diseases, and its application in estimation of cardiac autonomic nervous system activity. All of these topics have been addressed intensely in articles published in the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology during the last two years. In healthy subjects, the sinoatrial node located at the posterior wall of the right atrium initiates each beat of the heart. Due to the unstable membrane potential of the myocytes located in this region, action potentials are generated periodically at a fairly constant frequency. This relatively constant frequency generated by the autorhythmicity of the sinoatrial node is modulated by many factors that add variability to the heart rate signal at different frequencies. According to the Task Force of The European Society of Cardiology and The North American Society of Pacing and Electrophysiology (47a) these frequencies are classified into 1) ultra-low frequencies (ULF; >5-h cycle length) that include the circadian rhythm (6, 9, 34, 54); 2) very low frequencies (VLF; >25-s cycle length) that are supposed to be affected by temperature regulation (1, 7, 34, 52, 54) and humoral systems (9, 36); 3) low frequencies (LF; >6-s cycle length in humans) that are sensitive to changes in cardiac sympathetic (and presumably parasympathetic) nerve activity (27, 30); and 4) high frequencies (HF; 2.5- to 6.0-s cycle length in humans) that are synchronized to the respiratory rhythm (5) and are primarily modulated by cardiac parasympathetic innervation (38).The most prominent oscillation in the ULF band of the heart rate spectrum is the circadian rhythm. The autonomic nervous system contributes significantly to circadian heart rate variability. Using long-term recordings in conscious rabbits, Barrett et al. (6) demonstrated a strong circadian rhythm in heart rate, mean arterial blood pressure, renal blood flow, and renal sympathetic nerve activity. The importance of this study is that it clearly demonstrates that sympathetic nerve discharges exhibit a strong circadian rhythmicity. The paraventricular nucleus of the hypothalamus (PVN) appears to play a central role in mediating the circadian rhythm of autonomic nervous system activity. First, GABAergic and glutamatergic neurons project from the suprachiasmatic nuclei of the hypothalamus (SCN) to spinal-projecting neurons of the PVN (12). The SCN is the major central oscillator that triggers the day/night cycle. It receives photic input from the retina (47) and drives many neuroendocrine, metabolic, autonomic, and behavioral circadian rhythms (14, 16, 21, 31, 35, 44, 46, 50). In addition, microinjections of the inhibitory neurotransmitter GABA into the PVN of anesthetized rats elicit dose-dependent decreases in renal sympathetic nerve activity, whereas bicuculline (a GABA antagonist) increases renal sympathetic nerve activity (56). Second, from the PVN, neurons project to the nucleus of the solitary tract (that integrates inputs from the baroreceptors), the nucleus ambiguus (origin of preganglionic parasympathetic neurons to the heart), the rostroventrolateral medulla (location of sympathetic premotor neurons), and the intermediolateral cell column of the thoracolumbar spinal cord (location of preganglionic sympathetic neurons). Thus PVN neurons can modulate autonomic nervous system activity by sending inputs to major sites of autonomic nervous system regulation. As an example, a pivotal role of the PVN for sympathoexcitation during parturition was recently demonstrated in sheep. The increase in sympathetic nerve activity that accompanies birth in maternal animals was prevented by stereotactic lesioning of the PVN (43). Taken together, a major component of the circadian heart rate variability is elicited by diurnal fluctuations in autonomic nervous system activity, generated by corresponding fluctuations of neuronal activity within the PVN, which depend on circadian inputs originating from the SCN.It has been suggested that thermoregulation affects VLF heart rate variability (10, 26). Cooling the heart causes bradycardia, a mechanism used in heart surgeries. Conversely, fever is known to increase heart rate. Raising body core temperature from 36.0 to 36.6°C caused an increase in heart rate by almost 40 beats/min in male subjects (1), whereas acutely reducing ambient temperature from thermoneutral conditions (35°C) to 29, 23, and 17°C, reduced heart rate from 400 to 250 beats/min in 8-day-old rats (7). In addition, lowering temperature in the isolated working rat heart from 37 to 31°C reduced heart rate from 332 to 215 beats/min and markedly increased heart rate variability (28), indicating that parts of the temperature effects on heart rate and heart rate variability are independent from the autonomic nervous system. In contrast to the tachycardia that accompanies acute elevations in temperature, chronically raising ambient temperature in adult rodents from a standard housing temperature of 21-23°C to thermoneutral conditions (29-30°C) reduced heart rate by roughly 50 beats/min in rats (34) and by 200-300 beats/min in mice (54). The authors of these articles (34, 54) suggested that standard housing temperatures are associated with cold stress that causes parallel activation of brown adipose tissue, cardiac, and vasomotor sympathetic drives that elicits nonshivering thermogenesis and tonically elevates heart rate and arterial blood pressure. These and other studies indicate that both direct effects of temperature on pacemaker activity of the sinus node (28) and indirect effects mediated via the autonomic nervous system (11, 25, 51, 55) mediate temperature effects on heart rate and heart rate variability. Thus fluctuation in temperature is an important source of heart rate variability that should not be underestimated. In a more recent study, this was taken into account by core body temperature correction of heart rate variability (3).Endocrine factors affecting heart rate variability include thyroxine, reproductive hormones, the renin-angiotensin system, steroids, and others. Chronic subcutaneous infusion of angiotensin II in rats markedly increased blood pressure and heart rate variability, expressed as standard deviation (9). In contrast, chronic corticosterone treatment is likely to reduce baroreflex-mediated heart rate variability, because baroreceptor-heart rate (39) and baroreceptor-renal sympathetic nerve activity reflex sensitivity (41) were blunted in chronically corticosterone-treated rats. Furthermore, an interaction between angiotensin II and glucocorticoids was recently described. Intracerebro-ventricular microinjections of angiotensin II AT1 receptor antagonists caused marked decreases in mean blood pressure and heart rate in rats chronically treated with corticosterone but not in control animals (40). This interaction is likely to take place in the central nervous system, because peripheral angiotensin II AT1 receptor blockade did not alter the effects of betamethasone treatment on blood pressure, heart rate, and baroreceptor-heart rate reflex sensitivity in newborn lambs (42).Adenosine is a substance less known to affect heart rate variability. It is produced locally in the heart (53) and binds to A1-adenosinergic receptors, which are among the earliest expressed G protein-coupled receptors in the heart (36). The A1-adenosinergic agonist N6-cyclopentyladenosine dose dependently reduced heart rate in murine embryos, whereas 1,3-dipropyl-8-cyclopentylxanthine, an A1-adenosinergic antagonist, increased heart rate (36). Adenosine also exerts central nervous system effects in various brain areas (15, 20). Microinjections of adenosine into the nucleus of the solitary tract of awake rats caused dose-dependent changes in heart rate: low doses (0.01 nmol) produced a bradycardic response, whereas high doses (2.5-5.0 nmol) elicited a tachycardic response (15). Thus adenosine may indeed be involved in the regulation of heart rate and modulate heart rate variability via local cardiac and central nervous system effects. It has been proposed that the intrinsic cardiac nervous system plays an active role in regulating cardiac function (4, 37, 45, 57). This nervous system consists of sympathetic and parasympathetic neurons and interconnecting local circuits (37). Neurons in the canine right atrial ganglionated plexus (RAGP) spontaneously generate activity even after chronic cardiac autonomic denervation (45). Right atrial neurons in patients undergoing coronary artery bypass surgery generated spontaneous activity that was unrelated to the cardiac cycle but sensitive to changes in systemic arterial pressure, indicating that these neurons receive pressure-sensitive sensory inputs (4). In addition, it has been suggested that substance P acts as a neuromodulator and neurotransmitter in intracardiac ganglia of the guinea pig, modulates the response to vagal inputs, and triggers action potentials at the site of parasympathetic ganglia independent of acetylcholine (57). Furthermore, the right atrial (RAGP) and the posterior atrial ganglionated plexus (PAGP) appear to have different functions. Ablation of the PAGP reduced vagally mediated bradycardia by 26%, whereas RAGP ablation completely abolished this response. Inhibition of sympathetically mediated tachycardia by vagal stimulation was attenuated by ablation of either plexus (37). Thus parasympathetic efferent neurons are primarily located in the RAGP, whereas prejunctional parasympathetic-sympathetic interactions also involve neurons within the PAGP (37). The spontaneous activity of neurons in the intrinsic cardiac nervous system, even after cardiac denervation (45), suggests an active role of this system in regulating heart rate. However, the impact of the intrinsic cardiac nervous system on heart rate variability remains to be elucidated. The importance of the autonomic nervous system for heart rate variability in humans becomes apparent in patients following cardiac transplantation, in whom heart rate variability is markedly reduced (49). Although reinnervation is possible after months and years, initially transplanted hearts can be considered to be denervated. Thus the reduced heart rate variability in cardiac transplanted patients (49) underlines the importance of an intact autonomic innervation for spontaneously occurring heart rate variability. A major component of the chronotropic effect of the autonomic nervous system is linked to cAMP. Intracellular cAMP increases the inward current of Na+ (funny current, If), which determines the rate of the slow diastolic depolarization that precedes each action potential. The activity of adenylate cyclase and thus intracellular cAMP levels are increased by stimulation of sympathetic β1-adrenergic receptors and decreased (via a Gi protein) by stimulation of parasympathetic muscarinic receptors. Thus cardiac sympathetic innervation increases the rate of the slow diastolic depolarization and accelerates heart rate, while cardiac parasympathetic innervation elicits opposite effects. Interestingly, parasympathetic-mediated changes in heart rate occur much faster than sympathetic-mediated effects on heart rate (27, 30, 47a). As a result, cardiac sympathetic nervous system activity can only affect LF components of heart rate variability, whereas the parasympathetic nervous system can also modulate HF components. A hitherto unsolved question in this context is if the rapid heart rate response to parasympathetic stimulation compared with the slow effect of sympathetic inputs is due to 1) different kinetics of β1-adrenergic vs. muscarinic receptors, 2) different kinetics of adenylate cyclase vs. phosphodiesterase, the enzyme that cleaves cAMP, or 3) fast parasympathetic-mediated opening of KACh channels (via muscarinic receptors and a GK protein). Support for the latter possibility comes from experiments in the rabbit sinoatrial node that demonstrated that activation of KACh channels contributes to the initial slowing of heart rate as a result of vagal stimulation (8).On the basis of the different frequency response characteristics of sympathetic and parasympathetic modulation of heart rate, frequency analysis of heart rate variability is often used as a tool to determine "autonomic balance" or sympathetic and parasympathetic nervous system activity (27, 47a). As an example, the wavelet transform was recently used to determine cardiac autonomic responses to reperfusion in patients with thrombolysis after coronary thrombosis. Depending on the location of the infarct, marked alterations in LF or HF spectral power of heart rate or in the LF/HF ratio was observed in all successful reperfusions (48).The HF component corresponds to the frequency of respiration and is driven by the vagus as indicated by the strong respiratory pattern of cardiac vagal motoneurons in the nucleus ambiguus (38). The LF component has been ascribed to sympathetic modulation of cardiac pacemaker activity, because a variety of studies demonstrated that acute interventions that increase sympathetic nervous system activity, such as orthostatic perturbations (17, 19, 33), mental stress (32), or handgrip exercise (13, 24) increases LF spectral power of heart rate (27, 30). In addition to acute perturbations of cardiac sympathetic nerve activity, feedback oscillations generated by the baroreceptor reflex also appear to contribute to LF spectral power of heart rate as it was demonstrated that sinoaortic denervation markedly reduces the LF component (27, 30). Despite the strong modulation of heart rate by the autonomic nervous system, the LF and HF spectral components of heart rate variability may not always be very reliable markers for cardiac sympathetic and parasympathetic "tone" (30). In a recent study, muscle sympathetic nerve activity was recorded together with heart rate variability during application of lower body negative pressure that is known to increase muscle sympathetic nerve activity (17, 33). At higher levels of lower body negative pressure (-15 mmHg), both muscle sympathetic nerve activity and relative LF spectral power of heart rate increased significantly, whereas HF spectral power decreased (17). These findings suggest that LF spectral power reflects cardiac sympathetic "tone." However, no correlation within subjects was found between changes in LF/HF ratio and muscle sympathetic nerve activity (17). Thus heart rate variability does not reliably reflect the sympathetic response to orthostatic stress. Respiration-related fluctuation of heart rate (respiratory sinus arrhythmia) is probably the most often investigated component of heart rate variability, as it is believed that this component reflects respiration-driven vagal modulation of sinus arrhythmia (27). In a recent study, Rentero et al. (38) recorded the electrical activity from cardiac vagal motoneurons in the nucleus ambiguus. Firing of these neurons was modulated by the central respiratory cycle. This and other studies support the view that respiratory sinus arrhythmia is generated by central coupling of the respiratory oscillator with autonomic centers in the brain stem. However, a mechanical cardiopulmonary coupling as a source of respiration-related heart rate variability has also been suggested (5). The Bainbridge reflex causes a tachycardia in response to hypervolemia. This reflex is initiated by atrial mechanoreceptors and uses efferent sympathetic and parasympathetic pathways to modulate heart rate in response to changes in central venous pressure (23). Thus respiratory changes in central blood volume cause corresponding respiratory fluctuations in cardiac autonomic nervous system activity via the Bainbridge reflex. Only the parasympathetic component of the efferent pathway of the reflex can contribute to respiratory sinus arrhythmia, because sympathetic actions on heart rate are too damped to follow the respiratory frequency. The gain and phase of the transfer function between respiratory changes in lung volume and R-R intervals of the ECG were calculated in human subjects during graded changes in central blood volume (5). At the respiratory frequency, the phase was -180 degree, indicating that an inspiratory increase in central blood volume was associated with a decrease in R-R interval (increase in heart rate). Furthermore, the gain of the transfer function at the respiratory frequency steadily increased with increasing central volumes (except at the highest volume). Both of these findings confirm the presence of the Bainbridge reflex in humans (5). Thus, in addition to the central coupling of respiratory oscillators with cardiovascular centers, the Bainbridge reflex may contribute to respiration-related heart rate variability by mechanical cardiopulmonary coupling. There is general agreement that low heart rate variability is an unfavorable prognostic marker for cardiovascular diseases, such as diabetic autonomic neuropathy, hypertension, myocardial infarction, and heart failure (18, 22, 27, 29, 47a). Heart rate variability (variance of R-R intervals) was reduced in patients with mild hypertension (29) compared with normal values (1,134 ± 202 vs. 3,466 ± 1,018 ms2) provided by the Task Force (47a). In the rat model of myocardial infarction-induced congestive heart failure, Francis and colleagues (18) reported loss of spontaneous heart rate variability 6 wk after coronary artery ligation. Interestingly, reduced heart rate variability was also observed in a rat model of depression that is based on chronic (4 wk) mild stress application (22). Because depression is an independent risk factor for coronary artery disease, this finding may realistically model a human disease process. The reduction in heart rate variability was abolished by β-adrenergic receptor blockade, indicating that the reduced heart rate variability in this model of depression is related to elevated cardiac sympathetic tone (22).In summary, heart rate variability is generated by multiple factors not exclusively limited to the autonomic nervous system. Specific frequency components of heart rate variability mirror acute perturbations of the autonomic nervous system but do not always reflect autonomic nervous system activity. Simple statistics of heart rate variability, such as the standard deviation of R-R intervals in the ECG, can reliably predict the prognosis of cardiovascular diseases.I thank Dr. R. McAllen for critically reviewing the manuscript. References 1 Aoki K, Stephens DP, and Johnson JM. Diurnal variation in cutaneous vasodilator and vasoconstrictor systems during heat stress. 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The Pediatric Role in the Care of Children in Foster and Kinship Care

In September 2010, 408,425 children and adolescents resided in foster care. Recent legislation highlights an increasing focus on involving pediatricians in supporting children in foster care and defines specific requirements relevant to the role of pediatricians. After completing this article, readers should be able to: Foster care is intended to provide a temporary haven for children during a time of family crisis when children are at imminent risk for harm. The goals of foster care are to promote child health, safety, permanency, and well-being. Foster care also has the mission of building on family strengths and providing birth parents with the services they need to reconnect (reunify) with their children. Because children fare best in stable and nurturing families, there has been an increased emphasis in the past decade on shortening the time to permanency through reunification, placement with relatives, and adoption. Foster care also has the obligation to prepare youth for independent living when none of these permanency options is possible. In some states, more than one third of children in foster care are in court-ordered (formal) kinship placements, arrangements in which the related (kin) caregiver may or may not be a certified foster parent. Even outside the child welfare system, somewhere between 4% and 8% of children reside with members of their extended family, neighbors, or friends for a variety of reasons. During the past decade, several studies were published reporting that children experience greater placement stability in kinship care than in nonrelative foster care, and that kin caregivers report fewer child behavior problems. Other data indicate that children in kinship care have as many issues as children in foster care, and that kinship caregivers are older, are less healthy, and have less access to services than nonrelative foster parents. However, recognizing that maintaining a child’s ties to his or her family of origin holds advantages for the child, relatively more children are being placed in kinship care as a result of child protective investigation. Other children are spending brief amounts of time in foster care while child welfare attempts to identify and investigate kinship resources. The definition of kin has expanded to include nonrelatives, such as family friends, acquaintances, and neighbors. There is little information about the outcomes of reunification with parents or kinship care, including child health and mental health outcomes and the percentage of kinship homes that undergo disruption. The vast majority of kinship placements are without oversight or subsidy, although recent federal legislation was intended to improve financial support for this group of caregivers. Children in foster care are classified as children who have special health-care needs by the American Academy of Pediatrics (AAP) because of their high prevalence of medical, emotional, behavioral, developmental, educational, and dental health-care problems. Most pediatric practitioners will encounter children and adolescents in foster or kinship care in their practices. It is important that pediatricians be familiar with the effects of childhood trauma and adversity, separation from family, and ongoing uncertainty on child behavior, mental health, and development. Pediatricians are in a unique position to identify problems, make appropriate referrals, and offer support and advice to caregivers. Foster care ideally should be developmentally appropriate and child-centered, and pediatricians can play a crucial role in offering developmentally sound advice and emotional support to caregivers about parenting traumatized children and children who have significant behavior problems. Pediatricians also should suggest ways to promote placement stability and successful permanency. Most maltreated children are not removed from their birth parents, but they appear to have the same health issues as children in foster and kinship care. The knowledge and skills that pediatricians bring to the care of children in foster and kinship care also apply to the larger population of children whose families are involved with child welfare agencies. Of 3.3 million child abuse and neglect reports in 2010, 436,321 (22%) were substantiated, and 254,000 children were removed to foster care. Over the past decade, the increasing trend toward keeping children with their birth parents or with kin caregivers after child protective investigation has reduced the total number of children in foster care. In the United States, on September 30, 2010, 408,425 children and adolescents resided in foster care, 26% in a relative (kinship) foster home, 48% in a nonrelative foster home, and 9% in either a group home or residential care setting. Of the remainder, 4% lived with a preadoptive family, 5% were on a trial discharge with their parents, and 2% were listed as “run-away.”Estimates suggest that more than 700,000 individual children have spent some time in foster care during the preceding 12 months. Census data indicate that approximately four to eight times as many children and teenagers live in informal, unregulated kinship care without child welfare involvement. Approximately 40% of those in foster care are teenagers, whereas 30% are children under age 5 years. Children in foster care range in age from birth to 21 years, although 47 states still emancipate adolescents at age 18 years. Minorities are represented prominently in foster care. In 2010, 29% of children were of African American heritage, 21% Hispanic, 41% white, and 5% of two or more races. Significant concern exists that the overrepresentation of minority children reflects bias in child protective referrals, investigation, and removal, as well as a lower likelihood of reunification after removal. Discrete subpopulations in foster care that present with unique health needs include children who have multiple handicaps, teenagers involved with juvenile justice, pregnant and parenting teenagers, and unaccompanied refugee minors from countries ravaged by war or severe internal strife. The average length of stay in foster care in 2010 was 25 months, with a median of 14.5 months. The lower median is attributed to more intensive permanency planning, resulting in shorter times to reunification or placement with extended family. However, the higher mean is affected by the 25% of children who remain in care for years. Length of stay is affected by several factors: the biological family’s cooperation with the individualized case plan for their family; the availability of appropriate extended family to care for the child; diligence in permanency planning by child welfare; and the challenges of finding adoptive resources for older children, minority children, large sibling groups, and children who have significant behavioral and developmental problems. Longer stays in foster care are associated with a reduced likelihood of reunification and an increased number of placements. Approximately 50% of children and teenagers will experience more than one foster care placement, with approximately 25% having three or more placements. In 2010, of the 254,114 children who exited foster care, 51% returned to their parents and 14% went to a relative or guardian, whereas 21% were adopted and 11% aged out of foster care. The vast majority of the 27,854 individuals who aged out were emancipated at age 18 years. Because the long-term benefit of foster care placement is uncertain, admission to foster care is and should be difficult. Almost all children entering foster care are placed involuntarily by court order after child protective investigation. Child neglect, including lack of supervision or neglect of basic nutritional, educational, and medical needs, is the most commonly cited reason for placement. Overall, approximately 70% of admissions are for maltreatment. Teenagers tend to be placed for disruptive behaviors through either the juvenile justice system or as persons in need of supervision. Voluntary placements constitute less than 1% of admissions and often are made by families as a means of accessing treatment services for a child or teenager who has complex mental health or medical problems. Families whose children reside in foster care come from all walks of life, but financial poverty remains a pervasive common factor underlying foster care placement (>50% of children live with impoverished families before foster care). Poverty, however, extends beyond the financial to the lack of the normal, predictable, nurturing environment that promotes good developmental and emotional health. Most children have experienced childhood adversities beyond maltreatment, including exposure to significant violence in their homes (84%) or communities placement, report that of caregivers have parenting with mental health abuse or often lack have and high and are one third of birth parents to being or as children, and about the same percentage spent time in foster care. Children often have multiple caregivers before placement in foster care. of a child often with child welfare with the after have been when the child’s health and are at imminent that childhood trauma or multiple childhood and are associated with and long-term mental health, developmental, and health exposure and in the of protective the of the in a those of the involved in emotional and children entering foster care with their and adversities are children who have emotional, developmental, and health on and are but data indicate that stability in a nurturing and family promotes after childhood foster care is with and for children. high of family from the family of origin and all that is familiar is experience for many children, for children, placement in foster care may be the time they have stable placement in a foster home can promote the ongoing and to foster care may a child’s of highlights an increasing focus on involving pediatricians in supporting children in foster care. The to and of foster care to identify kinship resources at to foster care, promote and support kinship care, children in their of support American in keeping children foster care and resources for with a of independent for pediatric health states to health for children in foster care, pediatricians in the of such health improve health-care promote the of medical and health foster care system is in of providing children with nurturing families, but also complex in legislation of and but for the of foster care with which in to or child welfare by the foster care system remains by birth parents who have multiple problems, and and that appear to be in with child welfare is for and for is a complex multiple skills with Most however, more than of in many case for the biological family, parents the care of their children while to with or resources are mental health, parenting medical care, and and to promote also educational, developmental, medical, and mental health services for children, and support the foster parents in their care. birth parents are or to the for reunification, have the of supporting through the of permanency also are to children and a of to a family than their family of also and foster parents. have a with the system in their family court and the juvenile justice of a child from a family, the prepare a court the for the child or in foster care, the to court at to provide ongoing for the of placement and to their on of parents and children toward child in foster care is represented in court by a who may or may not be an on the In some states, in the court also may a special on of the who are not special many to the child’s for to the oversight with the court have the of on information to in a child remains in placement after or services for biological and at the case for a child in care to placement or an permanency is the court the permanency with the that such a is on the from all child welfare mental health and and the youth who is of age and developmental to on his or her for the child and childhood trauma remains parents are the and of the foster care system, and foster parenting is the Foster parents come from all walks of life, on tend to be be of lower have at a high be and have children of their have and most are by a to for children. foster parents with the of percentage of foster parents are and are to that can foster and 5% of foster families undergo to as resources for or children. However, most foster parents little about parenting children who have significant trauma and There are some studies that specific and for foster parents and birth parents as Foster and parenting for foster improve outcomes for children, but these have not for foster parenting are a for child in their care that is by individual The is by the child’s health needs, and the of the parenting The is to needs, and most and recent that approximately two of the of parenting a child in foster and of foster families are some of the most child welfare are in the foster care system in of and Foster families the of the for children and teenagers, but are to the system, and the birth family for the child’s care. remains with the birth a child is for but the foster care is for that a child’s needs are and the child is well of youth in foster care, reside in residential or group home placements, which can of child health services are but is The outcomes of group care have not been well and there to be in the of such of a child with his or her biological is the best for reunification, may be for the parents and The of the is Children who have been or by their parents may not in a setting. parents may not the need to focus on the child during and focus on their issues or with child parents may to the of the child with the and may which is and for children, and and the the with separation that may be for and through with by in a setting. to a or the home, the is before placement may for more with the birth but kin caregivers also may unique challenges they toward the birth are about or have to court-ordered to which the and is for of in which a mental health parents identify their child’s their child’s developmental parenting skills in parenting and to their child in an appropriate such as or still are not because such are and and is in which prepare birth parents for the stay on during the and with to the challenges associated with children may encounter adversities in foster care. in foster care placement, in or child care placement, separation from the of children entering or their foster home, by birth parents, a with their foster being or and court are but some of the children may an child, one can be to is as the of a child to foster care after reunification, placement with extended family or guardian, or adoption. on the to 30% of children to foster care, as a result of a of reunification with their birth parents. but percentage of undergo during an parents of their children in the care and of the or of can be as of a in which the the child’s the child either the age of majority or is parents to their children for more of involuntarily after at reunification have The can years, during which time but at reunification and permanency planning by federal legislation in states to a child has been in foster care for of the past and when there is reason not to the and in the with which they this federal child as a result of the of studies on childhood and placement has toward a to foster care, the is not to permanency on the of the out of foster care several Over of children adopted out of care are adopted by their foster parents, and 30% are adopted by kinship caregivers. to the most recent there were children out of foster care in 2010, of were for and resided in preadoptive children without an adoptive tend to be older, minority children, to be of large sibling groups, or to have significant emotional and behavioral problems, that to be to parents most often child welfare as an their and the reason for the of their family. some parents with child welfare either to remain with a or in that the child for the removal, whereas the of their family and for the resources that child welfare birth parents have trauma and their that have and lack the most basic of parenting and of their children may their of and welfare may children in a an foster home, or the home of a the of the court after child protective investigation. with kin caregivers is to be less the child has a with The in foster care may be with a of from child protective to health and members of the foster to foster care often are for the several a by most child welfare as a time of emotional for the and Children who have severe trauma may to behaviors that were in their but in the setting. The majority of children are by they not and or in in foster care often about they are in foster care, and children may for the of their about the of their parents and and their they will be in care, or when their parents will come for or when a will out of or parents may make they not or Other children about being in foster care, to their and of children and to foster parents and may their less birth as a in parenting or between for children and Children may not be for discharge from foster care or to a in foster care placement are for children, that a that of and for placements but include child behavior problems, foster between birth and foster parents, and a foster home may be or neglect a child’s needs, resulting in foster care is because the care is and nurturing foster a of and for the child, the child to the of family and to the The foster care placement is stable during the child’s time in care. The foster and birth and on of the The birth for at and of the services by child Child welfare the birth identify and on the family’s and the crisis that to the family’s is Children appropriate mental health and their parents in those services as the foster care experience not this in foster care are a have in foster care, whereas foster care through the juvenile justice system or are placed by a to their behaviors or to access appropriate mental health-care tend to have the placement they experience a variety of foster care time family group residential or and between foster care, home, juvenile percentage of teenagers are and have significant behavior teenagers may lack the to in or parenting teenagers are group who may be living with their children or placed from they have significant mental health issues or constitute a risk to their teenagers foster care as unaccompanied refugee having to the United from a variety of countries after or the of their majority of adolescents in foster care reside in their are is and they mental health services and adolescents in foster care have experienced childhood including maltreatment, as children in foster care. have and but their including and may be that the underlying remain in foster care are less to permanency, either through reunification or adoption. to parents or relatives, but many age out at age 18 years, or are to or placement care or group home care). to and for independent living is resources are Foster or kin families who remain in youth are their best and youth who identify and remain to foster parents, or appear to fare is about the outcomes of youth who have aged out is a of most youth have spent at one and many have an who are a decade removed from foster care are have with in and have high of mental health problems, including and studies indicate that with a of foster care are the and is the time during which the individual is to a stable in a of in and a larger of and in to in foster care, minority lack of and a lack of are outcomes of the of multiple and a of is from living in the of foster abuse and neglect, with separation and and a lack of role for result in a high prevalence of who are and to well are those foster youth who are and a multiple childhood health issues of children in foster care are in their of neglect, and and multiple childhood and childhood with the lack of protective the health of children in foster care. The defines children in foster care as children with special health-care needs because of their high prevalence of medical developmental dental problems, and behavioral, emotional, and mental health In of children in foster care have issues related to family about the health of the foster care population have to care, 30% to have at one medical and approximately have complex health problems. The for the high prevalence of health include medical neglect or lack of access to health services before foster of the to with child’s health needs, resulting in and the of childhood adversities on health. and developmental are and may be the result of the of and childhood or the result of studies report that the ongoing health of children in foster care are mental health and developmental problems. of children under age foster care with developmental in at one and to 70% of children age 5 have a mental health or behavioral are in the adversities and trauma children have experienced before foster care. that may have been in a or environment in a more setting. that significant behavioral of by developmental problems, to placement in emotional and mental health children foster care, their health not appear to improve The of the population the likelihood that they will to have access to information on admission foster care is foster parents have the of knowledge to as the health-care the foster system on to this complex most children in foster care have health in the of this also access to health-care because of in and of medical to in care may access to medical care, but mental health access for children in foster care. to support and foster parents about a child’s medical, developmental, and mental health needs and to appropriate treatment can to in placement when foster parents and requirements may and treatment and care can be is not However, has specific about who can for health-care on of a child in foster care. states, for of the guardian, who is the birth for including of In child welfare have in for and health-care should issues with their child welfare the health of the legislation states to health for children in foster care, is in in most with intensive care are because health-care the of care children children in foster care will their health-care as children who have special health-care needs in the of a pediatric medical The has a number of resources to pediatric but the of the medical home for the child in foster care are as The medical home should the health-care for children and teenagers in foster care by the on Foster from for Children and in Foster The are on the Foster was for by child mental health, and and youth in foster care. resources and may also be to pediatricians in with states and foster care for health brief of the health-care for children in foster care are listed in and should children and after to care, because often more health needs than one and they a between the and The admission health-care for all children, but for those with special health-care Children in foster care should have health-care and those for all children to all of their health developmental, educational, emotional and behavioral, and health-care encounter should include for child abuse and neglect in the placement. Foster that should be in to the children who have complex medical, developmental, or mental health problems, the may more health health is the most important health-care need of children in foster care. Children need and of mental health and to pediatric mental health of mental health-care basic should be in when and are two health needs of children in foster care. and may result in and multiple and are the most to be developmental for all children in foster care is not the pediatric should at a developmental to identify children in need of a some children developmental skills and in foster care, child who has behavioral or in should an It is that the with the child’s to that needs are and parents in most communities report that children in foster care have access to dental care, a high prevalence of significant dental are to with their health and dental to access issues for children in foster is a and in foster care. foster families have a of but the should not that they have in parenting children and teenagers who have past and ongoing In to the should issues specific to foster care, such as on the child’s parenting the of trauma on child supporting children through permanency planning, in placement, significant the need for and with birth parents to and and children should be about planning for their and with teenagers in foster care, have their to to a pediatric can foster parents the emotional while supporting an parenting for foster families and youth in foster care and can a foster care placement for a the also the birth and the child’s in these is the of the foster care with the as the case However, the pediatric medical home has an important role to play in that a child in foster care all health-care in a and that and youth in care all and in the health-care that health with child welfare to and information health-care are in are in a unique position to for in of care for children in foster care, in of the health in the can with their the and a and on in the of Children in Foster and the children and families for their and her at Pediatrics and the of for their and

Pediatrics in Review · review · 19 citationsread the source →

Willingness to participate in genomics research and desire for personal results among underrepresented minority patients: a structured interview study.

Patients from traditionally underrepresented communities need to be involved in discussions around genomics research including attitudes towards participation and receiving personal results. Structured interviews, including open-ended and closed-ended questions, were conducted with 205 patients in an inner-city hospital outpatient clinic: 48 % of participants self-identified as Black or African American, 29 % Hispanic, 10 % White; 49 % had an annual household income of <$20,000. When the potential for personal results to be returned was not mentioned, 82 % of participants were willing to participate in genomics research. Reasons for willingness fell into four themes: altruism; benefit to family members; personal health benefit; personal curiosity and improving understanding. Reasons for being unwilling fell into five themes: negative perception of research; not personally relevant; negative feelings about procedures (e.g., blood draws); practical barriers; and fear of results. Participants were more likely to report that they would participate in genomics research if personal results were offered than if they were not offered (89 vs. 62 % respectively, p < 0.001). Participants were more interested in receiving personal genomic risk results for cancer, heart disease and type 2 diabetes than obesity (89, 89, 91, 80 % respectively, all p < 0.001). The only characteristic consistently associated with interest in receiving personal results was disease-specific worry. There was considerable willingness to participate in and desire for personal results from genomics research in this sample of predominantly low-income, Hispanic and African American patients. When returning results is not practical, or even when it is, alternatively or additionally providing generic information about genomics and health may also be a valuable commodity to underrepresented minority and other populations considering participating in genomics research.

Journal of community genetics · 65 citationsread the source →

Ethnoracial and social trends in breast cancer staging at diagnosis in Brazil, 2001-14: a case only analysis.

Background: Policies for early detection of breast cancer, including clinical breast examinations and mammographic screening, were introduced in Brazil in 2004, but their effect on disease stage at diagnosis is unclear. We aimed to assess whether these policies have led to a decrease in the prevalence of late-stage breast cancer at diagnosis. Methods: In this case only analysis, using an anonymised nationwide hospital based-cancer registry network, we identified women aged 18-89 years who had been diagnosed with an invasive breast cancer in Brazil during 2001-14. We extracted individual patient-level data on patient demographics, tumour variables, and health-care provider variables for the centre where the patient was diagnosed. Our objectives were to estimate the prevalence of late-stage breast cancer (TNM stage III or IV) at diagnosis overall, across age groups, and by ethnoracial and social strata (ie, self-reported ethnoracial group, as white, black, brown, Asian, or Indigenous, and educational level, marital status, and region of residence) across the study period, and compare these estimates with international data from high-income countries (Norway and the USA). We used logistic regression to estimate odds ratios (ORs) for late-stage versus early-stage (TNM stage I or II) breast cancer at diagnosis in relation to relevant exposures, either minimally adjusted (for age, year of diagnosis, and region of residence) or fully adjusted (for all patient, tumour, and health-care provider variables). Findings: We identified 247 719 women who were diagnosed with invasive breast cancer between Jan 1, 2001, and Dec 31, 2014, with a mean age at diagnosis of 55·4 years (SD 13·3), of whom 36·2% (n=89 550) identified as white, 29·8% (n=73 826) as black or brown, and 0·7% (n=1639) as Asian or Indigenous. Prevalence of late-stage breast cancer at diagnosis remained high throughout 2001-14, at approximately 40%, was inversely associated with educational level (p value for linear trend <0·0001), and was higher for women who identified as black (minimally adjusted OR 1·61, 95% CI 1·53-1·70; fully adjusted OR 1·45, 95% CI 1·38-1·54) and brown (minimally adjusted OR 1·26, 95% CI 1·22-1·30; fully adjusted OR 1·18, 1·14-1·23) than those who identified as white. The predicted prevalence of late-stage cancer at diagnosis was highest for women who were black or brown with little or no formal education (48·8%, 95% CI 48·2-49·5) and lowest for women who were white with university education (29·4%, 28·2-30·6), but both these prevalences were higher than that of all women diagnosed with breast cancer in Norway before the introduction of mammography screening (ie, 16·3%, 95% CI 15·4%-17·2% in 1970-74). Similar ethnoracial and social patterns emerged in analyses restricted to the age group targeted by screening (50-69 years). Interpretation: The persistently high prevalence of late-stage breast cancer at diagnosis across all ethnoracial and social strata in Brazil, although more substantially among the most disadvantaged populations, implies that early detection policies might have had little effect on breast cancer mortality so far, and highlights the need to focus primarily on timely diagnosis of symptomatic breast cancer rather than on screening for asymptomatic disease. Funding: Newton Fund, Research Councils UK, and Conselho Nacional das Fundações Estaduais de Amparo à Pesquisa.

The Lancet. Global health · 56 citationsread the source →

The pleasure of art as a matter of fact

You have accessMoreSectionsView PDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditEmail Cite this article Nadal Marcos and Skov Martin 2018The pleasure of art as a matter of factProc. R. Soc. B.2852017225220172252http://doi.org/10.1098/rspb.2017.2252SectionYou have accessCommentThe pleasure of art as a matter of fact Marcos Nadal Marcos Nadal http://orcid.org/0000-0002-9341-4688 Department of Psychology, University of the Balearic Islands, Palma de Mallorca 07122, Spain [email protected] Google Scholar Find this author on PubMed Search for more papers by this author and Martin Skov Martin Skov Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Copenhagen 2650, Denmark Center for Decision Neuroscience, Copenhagen Business School, Copenhagen 2000, Denmark Google Scholar Find this author on PubMed Search for more papers by this author Marcos Nadal Marcos Nadal http://orcid.org/0000-0002-9341-4688 Department of Psychology, University of the Balearic Islands, Palma de Mallorca 07122, Spain [email protected] Google Scholar Find this author on PubMed and Martin Skov Martin Skov Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Copenhagen 2650, Denmark Center for Decision Neuroscience, Copenhagen Business School, Copenhagen 2000, Denmark Google Scholar Find this author on PubMed Published:21 March 2018https://doi.org/10.1098/rspb.2017.2252All other forms of perception divide a man, because they are exclusively based either on the sensuous or on the intellectual part of his being; only the perception of the Beautiful makes something whole of him, because both his natures must accord with it.— Schiller, 1793–1795, Letters on the Aesthetic Education of Man, p. 138, Letter 27Can art make us better people? Better members of society? In her recent article, 'Pleasure junkies all around! Why it matters and why "the arts" might be the answer: a biopsychological perspective', Christensen [1] claims that engaging with art can promote healthy choices, choices that balance short-term pleasure goals with long-term general well-being. She suggests that many modern life conveniences, such as social media, computer games or online shopping, have the potential to turn us into 'pleasure junkies' because they maximize short-term pleasures. But art, Christensen argues, is a safe choice and a means to remedy this unhealthy addiction to pleasure. Christensen's argument is grounded on three claims about the sort of pleasure we get from art. First, in contrast to low-level pleasure, which Christensen conceives as 'a mere perceptual stimulation leading to a rewarding sensation (food, sex, etc.)' ([1], p. 2), pleasure from art is presented as a kind of higher-order pleasure that engages 'broader neural networks implied in the attribution of meaning' (p. 2), presumably leading to 'long-term maintenance of healthy bodily function' (p. 2). Second, 'the arts do not induce states of craving without fulfilment—as do activities with reinforcement schedules which are prone to create habits and addictions such as intermittent variable ratio or interval reinforcement schedules (e.g. social media, gambling, football, extreme sports, drugs' (p. 4). Third, 'the arts do not search for a perceptual "Bliss point" […]. They do not just repeat over and over again a sensory stimulus that excites the senses and induces craving for more of a "pleasurable itch" (e.g. sugar, sexualized body displays, certain musical lyrics, tones; i.e. a perceptual "bliss point")' (p. 4).The claim, in a nutshell, is that the pleasure induced by art is different to the pleasure induced by food, sex, sports or drugs, because it is related to the balanced activation of brain systems related to short-term pleasure and long-term wellbeing goals, because it does not induce craving, and because it is not aimed at a perceptual 'bliss point'. This distinct sort of pleasure, according to Christensen, makes it possible for the arts to thwart the pernicious effects that the unhealthy urges and cravings licensed by 'today's mainstream acceptance of pleasure-seeking behaviour' (p. 5) have on individuals' lives and on societies. Such sweeping statements about art, food, sex, sports and society as a whole merit close examination. Christensen's primary claim that the pleasure induced by art is of a special kind, different to the pleasure induced by other activities is not supported by current understanding of what pleasure is. It is, moreover, contradicted by abundant empirical evidence. This evidence shows that pleasures, whatever their source, owe to activity in the same mesocorticolimbic circuit [2] and are encoded as a common neural currency [3]. As Kent Berridge and Morten Kringelbach put it: 'the brain mechanisms involved in fundamental pleasures (food and sexual pleasures) overlap with those for higher-order pleasures (e.g. monetary, artistic, musical, altruistic and transcendent pleasures) […] From sensory pleasures and drugs of abuse […] to monetary, aesthetic and musical delights, all pleasures seem to involve the same hedonic brain systems' ([4], p. 481). Thus, there is no evidence for specific brain regions or neural circuits related to the pleasure from art. Rather, the appreciation of art relies on brain mechanisms that evolved to appraise the value of biologically relevant objects in relation to internal homeostatic states [5]: 'Emotional reactions to music, further, activate the same cortical, subcortical and autonomic circuits, which are considered as the essential survival circuits of biological organisms in general' ([6], p. 6). In sum, the evidence shows that pleasure elicited by music and other art forms is no different in genesis and function to the pleasure induced by food, drugs and sex [7,8]. This is a matter of fact, not opinion. What supports Christensen's argument if not empirical evidence? In our view, her argument for the distinctness of art-induced pleasure seems based upon an oversimplified and devaluing conception of the pleasures of sex, food and sports, and a very narrow notion of art and its function. Christensen presents food, sex and sports as meaningless low-level sources of pleasure, and the arts as privileged vehicles for meaningful experiences. It is the personal and meaningful engagement with art—Christensen suggests—that fosters a balanced activation of brain systems related to short-term pleasure and long-term well-being goals. However, rarely—if ever—are food, sex and sports meaningless rewarding sensations. Contrary to Christensen's definition on page 2 of her article, pleasure—even sensory pleasure—is not simply reward, and never simply a sensation [4]. Indulging in food, sex or sports are meaningful and personally significant experiences that are not a matter of mere physical sensation. The experience of pleasure from food and sex is shaped by context, knowledge, expectations, anticipations, attitudes and beliefs that bring meaning to them [9–11]. Sex can be meaningful because it signifies physical connection with one's loved one, because it is cheating on someone, or deemed a sin. Likewise, eating is not about obtaining low-level pleasure. What we eat, the way we eat, what we believe about what we eat, where and whom we eat with, imbue eating with individual and social meaning, and shape the actual pleasure of eating [12]. On the other hand, encounters with art are not necessarily meaningful [13,14]. Actually, there is nothing intrinsically meaningful about engaging with art. Many laypeople lack the knowledge schemata required to engage meaningfully with abstract, cubist or contemporary art [15,16]. There are plenty of artworks people do not find meaningful or pleasant. Meaning making is not a special feature of art; it is a general feature of our species's cognition [17,18]. We can endow virtually any aspect of reality with meaning: sex, food, sports, a urinal, the shape of a cloud, an averted glance, someone's absence. Christensen's argument also rests on a historically and culturally narrow conception of art and its function. Art is presented as a circumscribed category of activities that elicit a unique sort of pleasant experiences: — The arts are set of activities of a special kind that share certain defining features distinguishing them from other activities: 'the arts push boundaries, surprise, reveal and excite both artist and spectator' ([1], p. 4).— Art encounters are positive, leading to 'pleasurable chills' and pleasurable experiences of understanding: 'The moment of meaning-assignation, also called "mastering" or "understanding" an artwork, is therefore a pleasurable experience' ([1], p. 4).— The pleasure elicited by art is special, because it does not involve craving for intense peaks: 'The arts do not search for a perceptual "bliss point" […] They do not just repeat over and over a sensory stimulus that excites the senses and induces craving for more of a "pleasurable itch"' ([1], p. 4).This characterization of the arts substantially overlaps with the notion of 'fine arts'. The core features of this characterization were instituted in the eighteenth century, after European intellectuals grouped certain activities into a distinct and autonomous collection, labelled 'fine arts'. To make sense of and promote this grouping, it became imperative to identify a common essence setting art apart from other activities [19,20,21]. One of the most popular proposals was that only art could produce a special sort of pleasure, sophisticated and polite [19,21]—a conception stemming not from any understanding of physiology, but from mere speculation. This limited historical and cultural scope renders this conception of the arts unfit for behavioural or neuroscientific research [19]. The category 'the arts' should not be mistaken for a natural kind. It is a historical convention, and has no direct biological correspondence. Moreover, this conception of art that Christensen espouses does not apply to art as practised in non-Western societies [19,22]. It does not even apply to Western art before the eighteenth century or after the nineteenth century [19,20,21]. First, art does not necessarily evoke pleasurable experiences. There are abundant artworks intended to arouse negative emotions [19,23], and to portray physical and moral ugliness [24]. Understanding art is not necessarily a pleasant experience: it can be an angering, disgusting or upsetting one [25]. Second, many artworks actually exploit repetition, bliss points and craving [26]. Repetition is a fundamental design feature of music and other performance arts [27]: In Relation in Space (1976) Marina Abramovic and Ulay ran into each other repeatedly for an hour; Ravel's Bolero is a 17 min-long instance of melodic and rhythmic repetitiveness. Anticipation and craving for bliss points are also essential to music [28]. In fact, the enjoyment of music is linked to intense feelings of anticipation and expectation caused by dopamine activity in the caudate nucleus (also involved in the rewarding aspect of food) [29,30], and peak pleasure states (bliss points) [31], caused by the release of dopamine and opioids in the brain's reward system (also involved in cocaine induced euphoria) [29,30]. Given the available evidence, therefore, there is no reason to believe that the pleasure from art is special or unique [32].In sum, Christensen's claim for the distinctiveness of pleasure from art is contradicted by empirical evidence, and her argument for the beneficial effects of art rests upon disputed foundations. Art's capacity to promote healthier choices and make us better people that can contribute to a better society remains as unconfirmed today as it was when Schiller speculated on art's power to harmonize human's conflicting sensuous and formal impulses. Christensen's argument is problematic even if intended to highlight hypothetical possibilities. Arguments about hypothetical possibilities should still rely on valid premises, and scientific hypotheses should be grounded on evidence, or at least in line with it. Otherwise, they are merely unfounded speculations. Scientific aesthetics is only just finding its footing and its place within cognitive neuroscience [33,34]. If evidence is ignored or rejected because it does not fit preconceived notions about art and its function, scientific aesthetics will become only an arena to promote and legitimize personally appealing notions of art by applying a scientific gloss over them. A proper scientific study of art needs to be grounded on empirical evidence and strong arguments that follow from solid premises [35,36]. Only then can scientific aesthetics provide reliable explanations for artistic and aesthetic behaviour, and thus make a significant contribution to the understanding of our human nature. Data accessibilityThis article has no additional data. Authors' contributionsBoth authors have contributed to conceiving, developing and writing the research presented in this paper, and approved it for publication. Competing interestsWe declare we have no competing interests. FundingThis research was supported by grant PSI2016-77327-P (MINECO/AEI/ERDF, EU).Footnotes© 2018 The Author(s)Published by the Royal Society. All rights reserved. References1Christensen JF. 2017Pleasure junkies all around! Why it matters and why 'the arts' might be the answer: a biopsychological perspective. Proc. R. Soc. B 284, 20162837. (doi:10.1098/rspb.2016.2837) Link, ISI, Google Scholar2Berridge CW, Kringelbach ML. 2013Neuroscience of affect: brain mechanisms of pleasure and displeasure. Curr. Opin. 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(doi:10.1016/j.plrev.2017.06.013) PubMed, ISI, Google Scholar Previous ArticleNext Article VIEW FULL TEXT DOWNLOAD PDF FiguresRelatedReferencesDetailsCited by Clemente A, Pearce M, Skov M and Nadal M (2021) Evaluative judgment across domains: Liking balance, contour, symmetry and complexity in melodies and visual designs, Brain and Cognition, 10.1016/j.bandc.2021.105729, 151, (105729), Online publication date: 1-Jul-2021. Chuan-Peng H, Huang Y, Eickhoff S, Peng K and Sui J (2020) Seeking the "Beauty Center" in the Brain: A Meta-Analysis of fMRI Studies of Beautiful Human Faces and Visual Art, Cognitive, Affective, & Behavioral Neuroscience, 10.3758/s13415-020-00827-z, 20:6, (1200-1215), Online publication date: 1-Dec-2020. Skov M and Nadal M (2020) A Farewell to Art: Aesthetics as a Topic in Psychology and Neuroscience, Perspectives on Psychological Science, 10.1177/1745691619897963, 15:3, (630-642), Online publication date: 1-May-2020. Kalpokas I (2019) Making the Theory Political A Political Theory of Post-Truth, 10.1007/978-3-319-97713-3_4, (87-121), . Kalpokas I (2019) Affective Encounters of the Algorithmic Kind: Post-Truth and Posthuman Pleasure, Social Media + Society, 10.1177/2056305119845678, 5:2, (205630511984567), Online publication date: 1-Apr-2019. Skov M (2019) Aesthetic Appreciation: The View From Neuroimaging, Empirical Studies of the Arts, 10.1177/0276237419839257, 37:2, Online publication date: H, I and (2020) A for We Aesthetic in Human Neuroscience, A and in A New for Arts, This March Article in 2018 The Author(s)Published by the Royal Society. All rights Citations and are available with

Proceedings of the Royal Society B Biological Sciences · editorial or comment · 24 citationsread the source →

Exploring Proof of Concept for a Novel Web-Based Self-Management Support Intervention for Polycystic Ovary Syndrome: Multimethod Study.

Background: Polycystic ovary syndrome (PCOS) is a common chronic hormonal condition affecting 8%-13% of women and individuals assigned female at birth. Symptoms may include subfertility, menstrual, skin, and metabolic problems, with long-term health risks including diabetes and cardiovascular disease. PCOS has a significant negative impact on mental health, quality of life, and well-being. We explored proof of concept for a web-based self-management support intervention, "Hope PCOS," designed to reduce anxiety and depression and increase positive well-being for women living with PCOS. Objective: We aim to pilot the intervention to test feasibility for web-based recruitment and delivery, acceptability, and potential to reduce anxiety and depression and increase positive well-being. Methods: Women with PCOS were recruited via social media with support from a patient advocacy charity and offered places on a 6-session cohort of the intervention. In a pre-post design, participants reported depression (Patient Health Questionnaire 9-Items), anxiety (Generalized Anxiety Disorder 7-Items), well-being (Warwick-Edinburgh Mental Wellbeing Scale), hope (SHS [State Hope Scale]), and gratitude (GQ-6 [Gratitude Questionnaire]) at baseline and 6 weeks. All participants who accessed 3 or more sessions were invited to a follow-up qualitative interview to explore user experience. Data from 8 interviews were thematically analyzed, and pre-post data were explored with descriptive statistics. Results: A total of 63 eligible women responded and were given access to the intervention. Three withdrew, leaving a baseline sample of 60, aged 20-58 (median 30, IQR 25-36) years. Further, 48 of the 60 started, of whom 46% (22/48) completed at least 3 sessions, and 29% (14/48) completed all 6. Additionally, 8 women (aged 25-38, median 29, IQR 26-35) years who completed between 3 and 6 sessions reported acceptability and experiences in exit interviews, including prioritizing self-care, developing a self-management mindset, setting motivating goals, improved mental health, self-compassion, reduced shame, openness about PCOS, preparedness for future health concerns, and continuing practice to consolidate behavior change. Furthermore, 11 women aged 25-43 (median 31, IQR 27-37) years, who completed 1-6 sessions (median 6, IQR 6-6), completed pre- and postintervention outcomes. Descriptive quantitative analysis indicated decreases in anxiety and depression and increases in hope agency, hope pathways, and gratitude. There was a meaningful (≥3 points) increase in well-being. Among patients with baseline and follow-up data, 73% (8/11) met clinical caseness for depression at baseline and 36% (4/11) post intervention. Conclusions: We explored proof of concept. Web-based recruitment and delivery online were feasible. We detected early signs of acceptability and potential benefits for anxiety, depression, and positive well-being that warrant testing in a controlled trial. Future research should assess the feasibility of a randomized controlled trial to evaluate effectiveness, acceptability, and cost-effectiveness.

JMIR formative researchread the source →

Effects of Mindfulness-Based Interventions on Self-compassion in Health Care Professionals: a Meta-analysis.

Objectives: Health care professionals have elevated rates of burnout and compassion fatigue which are correlated with poorer quality of life and patient care, and inversely correlated with self-compassion. Primary studies have evaluated the extent to which mindfulness-based interventions increase self-compassion with contradictory findings. A meta-analytic review of the literature was conducted to quantitatively synthesize the effects of mindfulness-based interventions on self-compassion among health care professionals. Methods: Twenty-eight treatment outcome studies were identified eligible for inclusion. Five cumulative effect sizes were calculated using random-effects models to evaluate differences of changes in self-compassion for treatment and control groups. Within and between group comparisons were evaluated. Sub-group and moderator analyses were conducted to explore potential moderating variables. Results: Twenty-seven articles (k = 29, N = 1020) were utilized in the pre-post-treatment meta-analysis. Fifteen samples (52%) included health care professionals and fourteen (48%) professional health care students. Results showed a moderate effect size between pre-post-treatment comparisons (g = .61, 95% CI = .47 to .76) for self-compassion and a strong effect size for pre-treatment to follow-up (g = .76, 95% CI = .41 to 1.12). The effect size comparing post-treatment versus post-control was moderate. One exploratory moderator analysis was significant, with stronger effects for interventions with a retreat component. Conclusions: Findings suggest mindfulness-based interventions improve self-compassion in health care professionals. Additionally, a variety of mindfulness-based programs may be useful for employees and trainees. Future studies with rigorous methodology evaluating effects on self-compassion and patient care from mindfulness-based interventions are warranted to extend findings and explore moderators.

Mindfulness · 50 citationsread the source →

Child and Adolescent Mental Health During the COVID-19 Pandemic: Results of the Three-Wave Longitudinal COPSY Study.

Purpose: The German population-based longitudinal COVID-19 andPsychological Health study monitors changes in health-related quality of life (HRQoL) and mental health of children and adolescents during the COVID-19 pandemic and identifies vulnerable groups. Methods: A nationwide, population-based survey was conducted in May 2020 to June 2020 (Wave 1), December 2020 to January 2021 (Wave 2), and September 2021 to October 2021 (Wave 3). In total, n = 2,097 children and adolescents aged 7-17 years were investigated using measures to assess HRQoL (KIDSCREEN-10), mental health problems (SDQ), anxiety (SCARED), depressive symptoms(PHQ-2), and psychosomatic complaints(HBSC-SCL). Results: The prevalence of low HRQoL increased from 15% prepandemic to 40% and 48% in Waves 1 and 2 and improved slightly to 35% in Wave 3 (all differences significant). Similarly, overall mental health problems increased from 18% prepandemic to 29% in Wave 1 and 31% in Wave 2 to 28% in Wave 3 (all differences significant, except Wave 3 vs. 2), anxiety increased from 15% prepandemic to 24% and 30% in Waves 1 and 2 and was still 27% in Wave 3. Depressive symptoms increased from 10% prepandemic to 11% and 15% in Waves 1 and 2 and were 11% in Wave 3. A group with low parental education, restricted living conditions, migration background, and parental mental health problems was at significantly increased risk of HRQoL and mental health impairments. Discussion: The prevalence of low HRQoL, mental health problems, and anxiety has been elevated throughout the pandemic. Thus, mental health promotion, prevention, and intervention strategies need to be implemented to support adolescents-particularly those at risk.

The Journal of adolescent health : official publication of the Society for Adolescent Medicine · 161 citationsread the source →

The socioeconomic gradient of alcohol use: an analysis of nationally representative survey data from 55 low-income and middle-income countries.

Background: Alcohol is a leading risk factor for over 200 conditions and an important contributor to socioeconomic health inequalities. However, little is known about the associations between individuals' socioeconomic circumstances and alcohol consumption, especially heavy episodic drinking (HED; ≥5 drinks on one occasion) in low-income or middle-income countries. We investigated the association between individual and household level socioeconomic status, and alcohol drinking habits in these settings. Methods: In this pooled analysis of individual-level data, we used available nationally representative surveys-mainly WHO Stepwise Approach to Surveillance surveys-conducted in 55 low-income and middle-income countries between 2005 and 2017 reporting on alcohol use. Surveys from participants aged 15 years or older were included. Logistic regression models controlling for age, country, and survey year stratified by sex and country income groups were used to investigate associations between two indicators of socioeconomic status (individual educational attainment and household wealth) and alcohol use (current drinking and HED amongst current drinkers). Findings: Surveys from 336 287 participants were included in the analysis. Among males, the highest prevalence of both current drinking and HED was found in lower-middle-income countries (L-MICs; current drinking 49·9% [95% CI 48·7-51·2] and HED 63·3% [61·0-65·7]). Among females, the prevalence of current drinking was highest in upper-middle-income countries (U-MIC; 29·5% [26·1-33·2]), and the prevalence of HED was highest in low-income countries (LICs; 36·8% [33·6-40·2]). Clear gradients in the prevalence of current drinking were observed across all country income groups, with a higher prevalence among participants with high socioeconomic status. However, in U-MICs, current drinkers with low socioeconomic status were more likely to engage in HED than participants with high socioeconomic status; the opposite was observed in LICs, and no association between socioeconomic status and HED was found in L-MICs. Interpretation: The findings call for urgent alcohol control policies and interventions in LICs and L-MICs to reduce harmful HED. Moreover, alcohol control policies need to be targeted at socially disadvantaged groups in U-MICs. Funding: Deutsche Forschungsgemeinschaft and the National Center for Advancing Translational Sciences of the US National Institutes of Health.

The Lancet. Global health · 26 citationsread the source →

Health outcomes in people 2 years after surviving hospitalisation with COVID-19: a longitudinal cohort study.

Background: With the ongoing COVID-19 pandemic, growing evidence shows that a considerable proportion of people who have recovered from COVID-19 have long-term effects on multiple organs and systems. A few longitudinal studies have reported on the persistent health effects of COVID-19, but the follow-up was limited to 1 year after acute infection. The aim of our study was to characterise the longitudinal evolution of health outcomes in hospital survivors with different initial disease severity throughout 2 years after acute COVID-19 infection and to determine their recovery status. Methods: We did an ambidirectional, longitudinal cohort study of individuals who had survived hospitalisation with COVID-19 and who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. We measured health outcomes 6 months (June 16-Sept 3, 2020), 12 months (Dec 16, 2020-Feb 7, 2021), and 2 years (Nov 16, 2021-Jan 10, 2022) after symptom onset with a 6-min walking distance (6MWD) test, laboratory tests, and a series of questionnaires on symptoms, mental health, health-related quality of life (HRQoL), return to work, and health-care use after discharge. A subset of COVID-19 survivors received pulmonary function tests and chest imaging at each visit. Age-matched, sex-matched, and comorbidities-matched participants without COVID-19 infection (controls) were introduced to determine the recovery status of COVID-19 survivors at 2 years. The primary outcomes included symptoms, modified British Medical Research Council (mMRC) dyspnoea scale, HRQoL, 6MWD, and return to work, and were assessed in all COVID-19 survivors who attended all three follow-up visits. Symptoms, mMRC dyspnoea scale, and HRQoL were also assessed in controls. Findings: 2469 patients with COVID-19 were discharged from Jin Yin-tan Hospital between Jan 7 and May 29, 2020. 1192 COVID-19 survivors completed assessments at the three follow-up visits and were included in the final analysis, 1119 (94%) of whom attended the face-to-face interview 2 years after infection. The median age at discharge was 57·0 years (48·0-65·0) and 551 (46%) were women. The median follow-up time after symptom onset was 185·0 days (IQR 175·0-197·0) for the visit at 6 months, 349·0 days (337·0-360·0) for the visit at 12 months, and 685·0 days (675·0-698·0) for the visit at 2 years. The proportion of COVID-19 survivors with at least one sequelae symptom decreased significantly from 777 (68%) of 1149 at 6 months to 650 (55%) of 1190 at 2 years (p<0·0001), with fatigue or muscle weakness always being the most frequent. The proportion of COVID-19 survivors with an mMRC score of at least 1 was 168 (14%) of 1191 at 2 years, significantly lower than the 288 (26%) of 1104 at 6 months (p<0·0001). HRQoL continued to improve in almost all domains, especially in terms of anxiety or depression: the proportion of individuals with symptoms of anxiety or depression decreased from 256 (23%) of 1105 at 6 months to 143 (12%) 1191 at 2 years (p<0·0001). The proportion of individuals with a 6MWD less than the lower limit of the normal range declined continuously in COVID-19 survivors overall and in the three subgroups of varying initial disease severity. 438 (89%) of 494 COVID-19 survivors had returned to their original work at 2 years. Survivors with long COVID symptoms at 2 years had lower HRQoL, worse exercise capacity, more mental health abnormality, and increased health-care use after discharge than survivors without long COVID symptoms. COVID-19 survivors still had more prevalent symptoms and more problems in pain or discomfort, as well as anxiety or depression, at 2 years than did controls. Additionally, a significantly higher proportion of survivors who had received higher-level respiratory support during hospitalisation had lung diffusion impairment (43 [65%] of 66 vs 24 [36%] of 66, p=0·0009), reduced residual volume (41 [62%] vs 13 [20%], p<0·0001), and total lung capacity (26 [39%] vs four [6%], p<0·0001) than did controls. Interpretation: Regardless of initial disease severity, COVID-19 survivors had longitudinal improvements in physical and mental health, with most returning to their original work within 2 years; however, the burden of symptomatic sequelae remained fairly high. COVID-19 survivors had a remarkably lower health status than the general population at 2 years. The study findings indicate that there is an urgent need to explore the pathogenesis of long COVID and develop effective interventions to reduce the risk of long COVID.

The Lancet. Respiratory medicine · 462 citationsread the source →

Identifying patterns of movement behaviours in relation to depressive symptoms during adolescence: A latent profile analysis approach.

Movement behaviour guideline adherence has been associated with lower depressive symptoms during adolescence, yet no studies have used person-centered approaches to examine this relationship. The purpose of the present study was to identify whether unique adolescent movement behaviour profiles exist, evaluate predictors of profile membership, and determine whether profile membership was associated with differences in depressive symptoms cross sectionally and longitudinally. This study involved secondary analysis of the public-use data from Wave 1 and Wave 2 of the National Study of Adolescent Health. Adolescents (N = 6436; 48% male) in grades 7 to 12 (Mage = 16.03 ± 1.75) completed measures to assess moderate-to-vigorous physical activity (MVPA), recreational screen time (ST), and sleep - collectively known as movement behaviours - and depressive symptoms. Latent profile analysis identified four profiles that had similar sleep patterns and were thus characterized by different levels of MVPA and ST: high MVPA/low ST (29%), high MVPA/high ST (4%), low MVPA/low ST (53%), and low MVPA/high ST (14%). Several socio-demographic variables were found to influence profile membership. After adjusting for covariates, findings revealed depressive symptoms were lowest among the high MVPA/low ST profile and this trend was evident one year later. Engaging in high levels of either MVPA or ST alone did not provide additive benefits for depressive symptoms compared to those who engaged in low levels of both MVPA and ST. These findings suggest intervention efforts should take an integrative approach to improve mental health outcomes among adolescents by considering each of the movement behaviours concurrently.

Preventive medicine · 23 citationsread the source →

[Breaking Bad News to Cancer Patients: Content, Communication Preferences and Psychological Distress].

Objectives Breaking bad news can be a very distressing situation for both patients and physicians. Physician communication behavior should therefore match patients' communication preferences. The aim of this study was to characterize the content of bad news from the patients' perspective. Patients' preferences for communication of bad news as well as the fit to communication behavior displayed by physicians were also investigated. Finally, consequences of a mismatch between patients' preferences and physician communication were investigated in relation to psychological distress in patients. Methods The sample consisted of N=270 cancer patients (mean age=56.8 years, 48% female) with various cancer entities and different stages of disease (n=115 patients with early stage of cancer, n=155 patients with advanced cancer). The content of bad news was assessed with a specifically developed list of questions. The Measure of Patients' Preferences Scale (MPP) was used to assess patients' preferences for communication of bad news. Patients further completed the NCCN Distress Thermometer (cancer specific distress), the Hospital Anxiety and Depression Scale (HADS- anxiety and depression) and the Demoralization Scale (DS-Scale) to gain information about psychological distress. Results Patients with early stage breast cancer received bad news M=1.6 times (SD=1.1, range: 1-5), patients with advanced cancers M=2.1 times (SD=1.6, range: 1-12). For 77% of early stage cancer patients and 70% of advanced cancer patients, the subjectively worst consultation was receiving the diagnosis and discussing treatment options. Patients' most important communication preferences were physicians' clinical competence and patient-centered communication, clear and direct communication and asking about patients information preferences. Patients in advanced stages report significantly more (29%) unmet communication needs than patients' in early stages (20%; p<0.01). Breaking bad news without considering patients' preferences was associated with higher psychological distress in patients. Conclusion Physicians should communicate in a patient-centered way to reduce mismatch with patients' preferences and thereby potentially reduce patients' psychological distress.

Psychotherapie, Psychosomatik, medizinische Psychologie · 14 citationsread the source →

Pathophysiology of the risk factors associated with osteoporosis and their correlation to the T-score value in patients with osteopenia and osteoporosis in the United Arab Emirates

INTRODUCTION Osteoporosis is a bone disorder, characterized by loss of bone strength because of an imbalance between the bone resorption and the mechanisms of bone formation, leading to increased fragility and fractures. Pathophysiological mechanisms underlying this disorder include an inadequate formation response during the remodeling process of bone formation, which is an essential factor in osteoporosis pathogenesis. This inadequacy is due to the activation of large numbers of osteoclasts as a response to initiation of hematopoietic precursor cells with failure of normal interaction with the osteoblastic lineage. This will lead to excessive bone resorption that may result in complete loss of trabecular structure and loss of template for new bone formation. The time required for osteoblastic replacement is longer than the resorption phase of bone remodeling by osteoclasts. Therefore, any increase in bone remodeling will lead to damaged architecture and loss of bone mass.[1] Recently, it has been estimated that more than 200 million people worldwide have osteoporosis. On the basis of a statistics from the International Osteoporosis Foundation in 2017, one in five men and one in three women over the age of 50 years will experience fractures during their lifetime because of osteoporosis. Furthermore, it has been found that an osteoporotic fracture occurs every 3s, with the most common fractures occurring at the hip, spine, and wrist.[23] Osteoporotic fractures may be the first manifestation of the disease, which is why it is called a silent disease. Risk factors of osteoporosis, decreased bone mineral density (BMD), and increased fragility fractures may be modifiable or non-modifiable. Among the modifiable factors are low body mass index (BMI), vitamin D deficiency, low calcium intake, excessive caffeine and alcohol consumption, smoking, sedentary life and low physical activity, endocrine disorders (such as estrogen deficiency and insulin-dependent diabetes mellitus or hyperparathyroidism), some drugs (such as corticosteroids), and previous history of fragility fractures. The non-modifiable factors include female gender, family history, race, and early menopause.[45] According to the World Health Organization (WHO) diagnostic criteria, osteoporosis is diagnosed by BMD at the hip or spine, which is below the young normal mean reference population by 2.5 standard deviations (SDs) or more. This is called the T-score, and osteopenia is diagnosed by BMD less than or equal to 1 SD.[6] The guidelines for osteoporosis screening vary greatly in various publications. In general, most organizations recommend that all adults older than 50 years of age with a history of fracture must receive BMD screening.[7] Dual-energy X-ray absorptiometry (DXA) at the hip or spine is the best test for measuring central BMD. An association is present between the T-score values in DXA in patients with osteoporosis or osteopenia and the risk of fractures. A fracture risk assessment tool (FRAX) was designed. It is estimated that for every 1 SD decline in spine BMD, the risk of having a spine fracture increases 2.3 times and the risk of having a hip fracture increases 2.6 times.[89] As the most common bone disease in humans, the prevalence of osteoporosis is steadily increasing due to a growing elderly population, and thus represents a major public health concern with reduced bone strength and a higher risk of fractures.[68] The prevalence of osteoporosis is steadily escalating due to increased life expectancy as a result of developed health services. According to the 2016 WHO report, in the United Arab Emirates (UAE), life expectancy at birth for men was 76 years and for women it was 79 years.[10] The UAE population projection showed that in 2011, 7% of the population were 50 years of age or over and less than 1% were 70 years of age or over. By 2050, it is estimated that 12% of the population will be 50 years or over and 2% will be 70 years or over.[11] MATERIALS AND METHODS Study design The study was performed in accordance with the International Conference on Harmonisation Good Clinical Practice guidelines. Ethical approval number UG-H-18-11-7-10 was obtained from the Research Ethics Committee of the college. The study was conducted on a population sample of national and nonnational people in the UAE. Both men and women were recruited in the study. Data were collected from the patients in six governmental and private hospitals. Research tools A total of 200 male and female participants between the age of 25 and 80 years were recruited in the study. Eighty percent of the sample were women and 20% were men. After obtaining the required consent, each participant was asked to fill a structured questionnaire consisting of 25 questions, which was used as the primary tool for data collection. The questions were formulated both in Arabic and English, it required 3–4min to be completed. BMD of the participants was assessed in the International Radiology Centre and correlated with their data in the questionnaires. DXA scan was used for the measurement of BMD. Data collection and data analysis After ensuring strict confidentiality, data were collected between March 20, 2016 and May 20, 2016. The following information was obtained: Demographic data (gender, age, race, BMI, and occupation) Family history of osteoporosis or osteoporotic fractures Social history and lifestyle, physical activity, and exposure to the sun Dietary habits such as calcium, caffeine, and soft drinks intake Medical history of diseases and medicines. For female participants, number of pregnancies, lactation, and age at menopause were included The following criteria were used to evaluate osteoporosis: Normal BMD: if T-score between +2.5 and –1 Osteopenia: if T-score between –1 and –2.5 Osteoporosis: if T-score below –2.5 The filled questionnaires were coded and data were analyzed statistically using the Statistical Package for the Social Sciences (SPSS) software (version 24; IBM Corporation, Newyork, USA). Spearman’s correlation test was carried out to assess the association between different variables in the study. A P value of less than 0.05 was considered significant. RESULTS Sociodemographic data The sociodemographic background of the study participants is listed in Table 1. A total of 200 participants were included in the study. The control group and the osteoporotic group consisted of 100 participants each, 20% of them were men, whereas 80% of the respondents were women. Table 1: Background demographic data of the respondentsBody mass index The patients with osteoporosis have significantly lower BMI than the control group (P < 0.05). Results showed that 72% of them have a BMI less than 25 kg/m2 (P < 0.05) [Table 2] [Figure 1].Table 2: Body mass index of the respondentsFigure 1: Body mass index (kg/m2) of the respondentsSmoking behavior Regarding smoking behavior, a significant value was evident between smoking and osteoporosis (P < 0.01) as 54% of the patients with osteoporosis were current smokers, whereas 72% of the controls had never smoked before [Table 3] [Figure 2].Table 3: Smoking behavior and intake of milk, coffee, and soft drinks by the respondentsFigure 2: Intake of milk and caffeine and smoking behavior by the respondentsDietary calcium intake The intake of milk and dairy products by the participants was used to assess the dietary calcium intake. The patients with osteoporosis have a significant low calcium intake (P < 0.01), whereas non-osteoporotic control significantly consume more milk and dairy products (P < 0.01). A positive correlation was found between the intake of milk and dairy products and the T-score value of the participants (P < 0.05) [Table 3] [Figures 2 and 3].Figure 3: Correlation between milk intake and T-score in patients with osteoporosisCaffeine consumption Caffeine intake was evaluated in this study by the amount of coffee, tea, or soft drinks consumed by the participants each day. The results showed that the patients with osteoporosis significantly consume more caffeine (P < 0.01). A negative correlation is present between the amount of caffeine intake and T-score value of the participants (P < 0.05) [Table 3] [Figures 2, 4, and 5].Figure 4: Correlation between tea/coffee intake and T-score in patients with osteoporosisFigure 5: Correlation between soft drinks intake and T-score in patients with osteoporosisExercise behavior and exposure to the sun Results showed a significant positive correlation between the duration of exercise and the T-score value of the participants (P < 0.05) [Table 4] [Figure 6].Table 4: Exercise behavior and exposure to sun of the respondentsFigure 6: Correlation between exercise duration and T-score in patients with osteoporosisRegarding the exposure to the sun, the results showed that 96% of the patients with osteoporosis were exposed to the sun for less than 15min, three to four times a week or not exposed at all, whereas most of the normal controls (72%) exposed their bodies to the sun for 16–30min/day, three to four times a week [Table 4] [Figure 7].Figure 7: Sun exposure behavior of the respondentsDiseases and medications Results of the study revealed that 46% of the patients with osteoporosis were diabetic, 42% of them were treated by antidiabetics, 18% had arthritis and 38% had been treated previously by corticosteroids [Table 5].Table 5: Distribution of patients with osteoporosis by their diseases and medicationsNumber of pregnancies and breastfeeding Female participants constituted 80% of the study sample, 75% of the females with osteoporosis were menopausal, 75% of them had three or more pregnancies, and 82.5% of them breastfed their children, whereas these values for the control group participants are 30%, 28%, and 33%, respectively. Results showed a significant positive correlation between the age at menopause and the T-score value of females with osteoporosis (P < 0.05) [Table 6] [Figure 8]. The distribution of patients according to the joint affected by Osteoporosis or Osteopenia is shown in [Figure 9] and [Table 7].Table 6: Distribution of female patients with osteoporosis by number of pregnancies and breastfeedingFigure 8: Correlation between age at menopause and T-score in female patients with osteoporosisFigure 9: Distribution of patients having osteopenia or osteoporosis in wrists, hips, or spineTable 7: Distribution of patients having osteoporosis and/or osteopenia in hips, wrists, and spineDISCUSSION To maintain normal bone structure, a remodeling process that consists of osteoclasts, removing old bone, and osteoblasts, synthesizing new bone, occurs. Hematopoietic progenitors produce osteoclasts, whereas mesenchymal stem cells called marrow stromal fibroblasts produce osteoblasts. This process is controlled by certain circulating hormones, growth factors, and locally produced cytokines through their effects on apoptosis of osteoblasts and osteoclasts. Estrogen deficiency or glucocorticoid excess leads to bone loss because of changes in the production of bone cells. This is caused by the prolongation of the life span of osteoclasts and the shortening of the life span of osteoblasts. On the contrary, drugs that aim to treat or prevent osteoporosis prevent apoptosis of osteoblasts and/or stimulate the apoptosis of osteoclasts.[12] The pathogenesis of osteoporosis is the consequence of various hormonal, genetic, dietary, lifestyle, and physical factors. Genetic factors mainly affect the BMD and bone formation, whereas low levels of estrogen increase parathyroid hormone, and local cytokines are mainly responsible for bone remodeling imbalance.[13] Age and gender In this study, 76% of the patients with osteoporosis were women at or above 50 years of age. Osteoporosis is usually considered a disease of the elderly with low BMD. In a recent study, most of the patients with osteoporosis were in the age groups of 45–49 and 50–54 years.[14] Previous studies showed that women were at an increased risk of developing osteoporosis because of their faulty behavior of physical inactivity, sun-avoidance behavior, low intake of dairy products, and poor diets.[151617] Body mass index The results of this study showed a significant number of patients of osteoporosis with BMI <25 kg/m2, where P < 0.05. Women that have low BMI are at a higher risk of developing osteoporosis. It is reported that one unit change in BMI has a larger effect on the risk of developing osteoporosis than most other modifiable risk factors. To help reduce the risk of osteoporosis, patients should be advised to maintain a weight within the normal range.[1516] The risk of osteoporotic fractures increases in adults who have low BMI of less than 20 kg/m2.[18] On the contrary, patients who are obese (BMI >30 kg/m2) are also at a high risk of developing osteoporosis and fractures because of the risk of repeated falls and the weakness of the skeletal muscles due to loss of its mass as a result of aging.[19] Exercise and physical activity The results of this study showed a significant correlation between the exercise time and the T-score value. Previous studies concluded that physical activity and exercises stimulate skeletal growth and bone strength.[45] Estrogen Estrogen deficiency has a critical effect on the pathogenesis of osteoporosis. The results of this study showed a significant positive correlation between the age at menopause and the T-score value of the female patients. Estrogen has a crucial role in bone formation and physiology. It stimulates the production of T cell cytokines, affects the osteoblastic cell by altering its production of receptor activator of nuclear factor-Kappa B ligand (RANKL) or Osteoprotegerin (OPG), inhibits the differentiation of osteoclasts by direct action, and stimulates the formation of bone performed by osteoblasts and osteocytes, which allows them to enhance their ability to respond to mechanical forces.[2021] Estrogen produces its effect through a specific cell surface receptor called the estrogen receptor alpha (ERα). This receptor binds and then transports estrogen into the nucleus of the cell where certain genes are then activated by the receptor–hormone complex. ERα receptors and estrogen receptor–related receptor alpha (ERRα) are found on the surface of osteoblasts. ERRα may play a supporting role in the regulation of bone cells.[22] Previous studies also suggest that sex hormone–binding globulin may play a significant role in regulating bone cells as well because it facilitates entry of estrogen into cells.[23] Because of the natural drop of estrogen level in postmenopausal women, they are at the highest risk of developing osteoporosis. A previous study showed that it is an increase in bone resorption that might be the driving force for bone loss during estrogen deficiency in postmenopausal women not impaired bone formation as was previously thought.[1] However, other studies indicated that both markers of bone resorption and formation also increased, leading to accelerated bone remodeling at menopause.[2425] Calcium intake and vitamin D Calcium and vitamin D are two pivotal contributors of bone formation and mineralization. The results of this study showed that the patients with osteoporosis have a significant low calcium intake, whereas controls significantly consume more milk and dairy products (P < 0.01). This significant result showed the importance of calcium intake. Results also established a positive correlation between calcium intake and the T-score value of the participants. Vitamin D plays an important role in maintaining calcium homeostasis and bone integrity as it is essential for intestinal calcium absorption.[26] It is estimated that over one billion people around the world have vitamin D deficiency.[2728] Sun exposure is considered as the source of vitamin D, the present results showed a significant value (P < 0.01) as 74% of the patients with osteoporosis exposed their bodies to the sun for 5min or less, three to four times per week, whereas 72% of controls exposed their bodies to the sun for 15–30min, 3 to 4 times a week. A previous study conducted in the UAE showed that 58.2% of the UAE nationals were vitamin D deficient compared to 45% of the patients from other nationalities.[29] In spite of living in sunny areas, such as UAE, Saudi Arabia, and India, young populations have a high prevalence of vitamin D deficiency because of insufficient knowledge and practice of vitamin D and its health implications.[3031] Decreased blood calcium level will lead to secondary hyperparathyroidism. This decrease may result from impaired intestinal calcium absorption due to vitamin D deficiency, aging, or other diseases. Calcitriol, the active form of vitamin D, stimulates the intestinal absorption of calcium and phosphorus. It has an inhibitory effect on the synthesis of parathyroid hormone as well. Therefore, calcitriol deficiency will lead to secondary hyperparathyroidism as well.[32] There is a clear evidence that the risk of having an osteoporotic fracture increases when vitamin D levels are below 50 nmol.[3334] However, a recent study showed that pathological macrophages produced by vitamin D receptor signaling play an important role in the development of myelofibrosis.[35] Smoking The results of this study showed that nicotine has a significant effect on the incidence of osteoporosis (P < 0.01). Smoking has been identified as a modifiable risk factor for low BMD and increased osteoporotic fracture risk.[3637] Smoking behavior should be evaluated when assessing the fracture risk and FRAX.[1638] The role of smoking in decreasing BMD is complicated; smoking is shown to be associated with other risk factors for osteoporosis such as decreased physical activity, low BMI, and poor diet.[38] Nicotine has both direct and indirect effects on BMD. The direct effect is on bone cell proliferation and is described to be biphasic, small doses have a stimulatory effect, whereas toxic large doses have an antiproliferative effect on the proliferation of osteoblasts.[39] This effect on osteoblasts is receptor mediated by the nicotinic acetylcholine receptors, where nicotine in low doses upregulates gene expression of alkaline phosphatase, type 1 collagen, and osteocalcin.[40] Nicotine produces an increased level of tumor necrosis factor α (TNFα) secretion that reduces bone formation by osteoblasts and increases bone resorption by osteoclasts. TNFα has a powerful osteoclastogenic effect through its stimulating effect on RANKL production and by intensifying osteoclasts production.[41] It is strongly supported that RANK/RANKL/OPG systems have a role in regulating bone resorption and the formation of osteoclasts.[42] The main predisposing factor for chronic obstructive pulmonary disease (COPD) has been found to be smoking. The most important factor in managing COPD continues to be the termination of smoking.[43] It has been shown in numerous studies that smokers with COPD have elevated levels of pro-inflammatory cytokines in the form of interleukin-6. In addition, TNFα levels are much higher in COPD smokers than in asymptomatic smokers. This indicates that COPD affects local and systemic inflammatory responses, which in turn affects bone remodeling.[4445] Nicotine has an indirect effect on BMD, which is caused by releasing calcitropic hormones and glucocorticoids, which leads to an increase in bone resorption.[43] Furthermore, smoking has been linked to an increase in the level of cortisol[4446] as well as a decrease in the level of estradiol.[47] Nicotine also harms intestinal calcium absorption, which might lessen the effectiveness of dietary calcium supplements.[48] Also, toxic carcinogenic metabolites of nicotine have also been found to increase osteoclast formation in rats.[49] Moreover, one hip fracture in eight postmenopausal women with osteoporosis is attributable to smoking. This correlation could not be explained by early menopause, low BMI, lower levels of exercise, or by the actions of nicotine on estrogen. This indicates that there is an independent negative effect of nicotine on BMD, which means that smokers lose bone at a faster rate than nonsmokers.[50] CONCLUSION Prevalence of osteoporosis is high in the UAE and is expected to grow due to increased life expectancy and faulty lifestyle of inadequate dietary habits, sun exposure, exercise behavior, and smoking. More intervention should be directed toward changing the modifiable risk factors in the patients with osteoporosis, and more studies should be directed toward osteoporosis in the UAE. Limitations of the study To make the study a polycentric research, it would require greater number of participants from all the emirates of the UAE. Financial support and sponsorship This work is self-funded by the authors. Conflicts of interest There are no conflicts of interest.

Journal of Pharmacy And Bioallied Sciences · 11 citationsread the source →

Combat sports and wellbeing: advancing health and inclusion in athletes and practitioners. An opinion paper

Historically, combat sports have been predominantly conceptualized within the framework of elite competition, emphasizing physical aptitude, technical proficiency, and strategic execution (1-3). Despite their traditional and peculiar constitutions and developments, disciplines such as judo, karate, taekwondo, wrestling, fencing, boxing, and mixed martial arts have commonly been associated with high-performance athletes striving for competitive excellence on national and international stages (1, 4-6). However, contemporary discourse increasingly recognizes their expansive role in contributing to physical and psychological well-being, and social inclusion of the practitioners (7, 8). This paradigmatic shift underscores the capacity of combat sports to function as inclusive and accessible modalities for fostering multidimensional health benefits across diverse populations, including individuals with disabilities and other marginalized groups (9-13).The interdisciplinary exploration of physical activity and health highlights the intricate interrelationship between structured sports engagement and holistic well-being (14). Whilst conventional team and individual sports have long been acknowledged for their physiological and psychosocial benefits, combat sports exhibit distinct characteristics that might amplify these advantages (15, 16). Within combat sports, the synergistic interplay of rigorous physical conditioning, the cognitive engagement, adherence to rules, competition dynamics, respect, externalizing emotions regulation, are intertwined with pedagogical and philosophical values, thus presenting a unique framework for enhancing psychological resilience, cognitive adaptability, and emotional control. Consequently, the systematic practice of combat sports has been increasingly examined as a way of promoting mental health, stress modulation, and social cohesion (17, 18).The inclusive nature of many combat sports programmes further accentuates their relevance in dismantling stereotypes, facilitating integration, and fostering equity and social integration (19-21). In fact, they demonstrated significant adaptability to accommodate individuals with disabilities (e.g., physical impairments, developmental, emotional, intellectual disorders), thereby ensuring equitable access and fostering empowerment (9, 22). Adapted judo, para-taekwondo, and other modified combat disciplines provide individuals with disabilities a structured platform to engage in physical activity, cultivate self-efficacy, and develop meaningful social connections within a supportive and adaptive environment (23). From a public health perspective, the integration of combat sports within community-based health initiatives offers a compelling opportunity to engage populations that may not traditionally participate in structured physical activity programmes (7, 8, 19). The distinctive accessibility of combat sports, which cater to practitioners of all skill levels (e.g., from novices to elite athletes) sets them apart from many other sports. While their structured progression, adaptability, and emphasis on holistic development make them a viable option for lifelong and intergenerational participation (19, 24, 25), the mentorship and pedagogical frameworks cultivate positive role modeling, discipline, and intrinsic motivation, which are integral for sustaining long-term adherence to health-promoting behaviors (8).Furthermore, the intersection between combat sports and mental health has increasingly emerged as a focal point within academic and clinical research (17) with empirical evidence suggesting an association between participation and enhanced self-regulation and self-efficacy, and reduction in anxiety and depressive symptomatology (8, 26, 27). In necessitating sustained focus, adaptability, and emotional equilibrium, combat sports inherently require cognitive and affective demands, which align closely with established psychological frameworks that underpin mental well-being (28, 29). Moreover, the integration of mindfulness techniques, stress management strategies, and resilience-building paradigms within combat sports training substantiates their potential as a non-pharmacological intervention for addressing various mental health challenges (e.g., autism spectrum and oppositional defiant disorders) (30, 31).Despite these advantages, the discourse surrounding combat sports and well-being necessitates a critical examination of inherent risks and potential challenges. Issues related to injury risk, hypercompetitive environments, eating disorders, sexual harassment, and the psychological stressors associated with high-intensity training warrant careful scrutiny (32-36). The implementation of evidence-based injury prevention protocols, the establishment of ethically responsible coaching methodologies, and the promotion of safe training environments are imperative to ensure that the benefits of combat sports are maximized while minimizing adverse outcomes. Against this backdrop, this opinion paper seeks to examine the role of combat sports in advancing health and social inclusion among athletes and practitioners. Through a synthesis of contemporary empirical findings, theoretical paradigms, and applied insights, this paper aims to contribute to the evolving discourse on the potential of combat sports as a catalyst for holistic well-being. By delineating the multidimensional impact of combat sports on physical, psychological, and social health, this paper endeavors to underscore their transformative potential as an instrument for fostering individual and community well-being within different populations. DiscussionWhilst an expanding body of research and an evolution in scholarly discourse is recognizing the combat sports’ broader implications for holistic well-being (30, 37), a rigorous evaluation of the investigation methodologies, the validity of hypotheses, and the translational potential of recent findings is necessary to contextualize their significance within the sports and public health sciences, considering their strengths, weaknesses, opportunities, and threats (Figure 1).----------------------------------------ADD FIGURE 1 ABOUT HERE----------------------------------------Empirical evidence robustly shows the positive impact of combat sports on physical fitness, motor coordination, and cardiovascular health (3, 38). These benefits are attributed to the high-intensity, intermittent nature of combat sports training, which enhances aerobic and anaerobic endurance, muscular strength, and neuromuscular control (39). However, concerns regarding injury risk, particularly in striking and contact-intensive disciplines such as boxing, taekwondo, and mixed martial arts, necessitate continued research into injury mitigation strategies, particularly those targeting concussion and repetitive head trauma (6, 35, 40, 41). Moreover, many combat sports have developed styles with reduced or simulated contact to minimize injury risk. For example, the French "boxe éducative" emphasizing technique and control, penalizing any violent behaviors (42) and the value and application of kata (i.e., forms; prearranged, pattern practices) to learning and adopting judo technique in a safe way educating the athlete culturally, to enrich her/him as a person (43).Beyond physical health, recent studies highlight the psychological benefits of combat sports, including reductions in anxiety and depression and improvements in self-efficacy, emotional regulation, resilience, and stress management (27, 44-47). Therefore, combat sports-based interventions for individuals with mental health conditions have yielded promising outcomes (23). Despite these encouraging findings, variability in study designs, participant demographics, and intervention protocols limits their external validity, underscoring the need for further rigorously controlled investigations. Furthermore, some authors claimed that combat sport athletes might present symptoms of low energy availability and high anxiety levels associated with competition- and injury-related psychological stressors, deficits in executive functions and neuropsychological impairments associated with occurrence of concussions, disordered eating and eating disorders associated with weight-loss, and might suffer offensive, frightening, hostile, degrading, humiliating experiences, or sexual harassment, which urge safeguarding actions (32-36).The role of combat sports in fostering social inclusion has gained empirical support, particularly in programmes aimed at individuals with disabilities and marginalized communities (25, 48). For instance, a recent systematic review shows that judo interventions adapted for intellectual disabilities help improve social integration and self-perception and enhance participants' quality of life (49). The development of para-combat sports demonstrates enhanced physical and motor abilities while providing psychosocial benefits to various populations with different disabilities, promoting social integration, self-perception, and community belonging (50, 51). However, longitudinal research is needed to assess the long-term retention rates and sustainability of these benefits. Furthermore, there is a need of studies focused on the most appropriate adapted rules to achieve a fairer competition for ensuring a sense of success in individuals with physical, emotional, mental, hearing or visual impairments participating in adapted sports competitions at local, national, and international levels. Methodological approaches in combat sports research encompass experimental, longitudinal, qualitative, and systematic review designs. While randomized controlled trials remain the gold standard for establishing causality, their application in combat sports research is constrained by ethical concerns, logistical challenges, and the inherently dynamic nature of training environments (52, 53). Consequently, many studies rely on observational designs, which, despite their value in identifying associations, are susceptible to confounding variables and biases (24, 54).Qualitative methodologies have provided critical insights into the lived experiences of combat sports practitioners, offering perspectives on psychological and social dimensions that are often overlooked in quantitative studies (28). Ethnographic research has been particularly instrumental in elucidating the role of combat sports in shaping identity, discipline, and personal development (55). However, limitations in reproducibility and generalizability highlight the need for mixed-methods approaches to generate a more comprehensive understanding of combat sports' impact (25, 56).Additionally, the incorporation of biometric and neurocognitive assessments, such as heart rate variability analysis, functional MRI, and salivary cortisol measurements, has advanced our understanding of the physiological and psychological mechanisms underlying combat sports participation (47, 57, 58). Despite their objective precision, these techniques often face challenges related to cost, accessibility, and limited sample sizes, necessitating the development of scalable and cost-effective methodologies for broader research application. Finally, recent studies show that virtual reality (VR) technology and digital platforms are increasingly becoming part of combat sports training methods. Due to COVID-19 restrictions, martial arts schools and organizations implemented hybrid or online training models, which allowed athletes to stay engaged. VR boxing programmes provide users with virtual sparring simulations to enhance their motor skills without needing physical interaction. Initial results indicate that VR training enhances response behavior in karate athletes (59). Digital adaptations offer great potential, especially for people with limited mobility or remote locations. However, further studies are necessary to prove their enduring effects on physical health and psychological and social aspects (59-61).Strengths and Weaknesses of Scientific HypothesesThe hypothesis that combat sports confer multidimensional health benefits is strongly supported by empirical evidence spanning physiological, psychological, and social domains (8, 62-64). The integration of physical exertion, cognitive engagement, and structured discipline inherent in combat sports aligns with established theories of exercise psychology, neuroplasticity, and social identity formation (65, 66). This multidimensional perspective provides a robust theoretical foundation for advocating combat sports as a health-promoting activity. Nevertheless, several limitations warrant consideration. The heterogeneity of disciplines, which vary highly in intensity, contact level, and training methodologies, is often inadequately addressed in research, leading to overgeneralized conclusions (17, 39). Often underexamined, individual differences in personality, motivation, and previous trauma history may strongly moderate the psychological outcomes of combat sports participation (35, 67, 68).Additionally, a research focus is needed on concerns regarding the potential for adverse psychological effects (e.g., anxiety, depression, disordered eating behaviors, burnout, and decreased self-esteem), particularly in competitive environments where performance pressure, extreme weight-cutting practices, and aggressive coaching styles are prevalent (69, 70). Indeed, a balanced perspective that considers both benefits and risks is essential for the development of evidence-based recommendations (10, 71).Future DirectionsTo enhance the field, future research should prioritize well-structured longitudinal studies that assess the long-term impact of combat sports participation on physical, psychological, and social health. Standardization of outcome measures, intervention protocols, and participant demographics would facilitate cross-study comparisons and strengthen the reliability of findings (72, 73). Moreover, interdisciplinary collaborations incorporating sports science, psychology, and sociology could provide a more holistic perspective on combat sports' broader implications on practitioners (74).From a policy perspective, to yield valuable insights into combat sports’ practical applications research should investigate their efficacy within public health, educational, and rehabilitation initiatives, particularly for underserved and vulnerable populations (23, 75, 76).Furthermore, while safety remains a primary concern, advancements in protective equipment, training methodologies, education for athletes, coaches, referees and tournament directors, and regulatory frameworks should be continually evaluated to optimize benefits while mitigating risks (40, 41, 58, 77, 78). Ethical considerations, particularly concerning athlete well-being and inclusive participation, should remain a central focus in both research and practical implementation (17, 34, 36).Therefore, key research challenges to be addressed are: 1. Injury risk and safety: a need for injury prevention strategies, especially for concussions and head trauma in striking sports. 2. Psychological wellbeing: risks of stress, anxiety, burnout, and negative self-perception in competitive environments. 3. Inclusion and accessibility: a need for more research on long-term social and psychological benefits for marginalized groups and individuals with disabilities. 4. Methodological limitations: lack of standardized protocols, variability in study designs, and limited reproducibility of findings. 5. Ethical and regulatory issues: concerns over coaching practices, extreme weight-cutting, and athlete wellbeing in high-pressure environments. 6. Technological innovations: more research required on the effectiveness of VR and digital training tools in combat sports. 7. Public health and policy: exploration of combat sports' role in health initiatives, rehabilitation, and educational programs. ConclusionThe evolving discourse on combat sports highlights their potential as a multidimensional tool for well-being promotion. While a substantial body of evidence supports their benefits, a critical examination of methodological limitations, scientific hypotheses, and practical applications is essential for further refine our understanding and enhance their effectiveness. Finally, this article makes a significant contribution not only to the field of martial arts but also to public health and sports psychology. Its interdisciplinary approach calls for scientific collaboration and methodological rigor, reinforces the need for evidence-based policies and can serve as a valuable guide for researchers and policymakers looking to integrate combat sports into strategies for promoting health and social inclusion.

Frontiers in Psychology · 12 citationsread the source →

Childhood trauma and posttraumatic stress disorder in a real-world Veterans Affairs clinic: Examining treatment preferences and dropout.

Objective: The Department of Veterans Affairs (VA) has promoted large-scale dissemination efforts of evidence-based psychotherapies (EBPs) for posttraumatic stress disorder (PTSD). In spite of efforts to make gold-standard treatments available to veterans, few veterans with PTSD receive a full course of psychotherapy. It is unclear if type of trauma experienced is related to treatment initiation and completion. This study aimed to identify patient factors, including experiencing childhood trauma that related to treatment preferences and dropout in a real-world VA PTSD clinic. Method: A chart review was conducted for veterans who were referred for individual EBPs for PTSD (N = 199). Extracted variables included demographics, PTSD symptoms, treatment preferences, and treatment completion/dropout. Results: Veterans choose to engage in individual EBP (48%), group treatment (11%), nontrauma focused psychotherapy (15%), or no psychotherapy (26%). Slightly over half of the veterans who began individual EBP completed it, with no statistical differences in completion rates for prolonged exposure and cognitive processing therapy. Childhood trauma was the second-most common type of trauma experienced, next to combat exposure. Those who completed EBP had higher rates of combat trauma (88%) than noncompleters (70%), and noncompleters (50%) had higher rates of childhood trauma than completers (29%). Regardless of trauma experienced, those who completed an EBP experienced substantial reductions in PTSD symptoms. Conclusions: Assessing veterans for childhood trauma and emotion regulation difficulties may be beneficial even in VA clinics where treatment is most often focused on combat trauma. (PsycINFO Database Record

Psychological trauma : theory, research, practice and policy · 16 citationsread the source →

Association of tiered restrictions and a second lockdown with COVID-19 deaths and hospital admissions in England: a modelling study.

Background: A second wave of COVID-19 cases in autumn, 2020, in England led to localised, tiered restrictions (so-called alert levels) and, subsequently, a second national lockdown. We examined the impact of these tiered restrictions, and alternatives for lockdown stringency, timing, and duration, on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and hospital admissions and deaths from COVID-19. Methods: We fit an age-structured mathematical model of SARS-CoV-2 transmission to data on hospital admissions and hospital bed occupancy (ISARIC4C/COVID-19 Clinical Information Network, National Health Service [NHS] England), seroprevalence (Office for National Statistics, UK Biobank, REACT-2 study), virology (REACT-1 study), and deaths (Public Health England) across the seven NHS England regions from March 1, to Oct 13, 2020. We analysed mobility (Google Community Mobility) and social contact (CoMix study) data to estimate the effect of tiered restrictions implemented in England, and of lockdowns implemented in Northern Ireland and Wales, in October, 2020, and projected epidemiological scenarios for England up to March 31, 2021. Findings: We estimated a reduction in the effective reproduction number (Rt) of 2% (95% credible interval [CrI] 0-4) for tier 2, 10% (6-14) for tier 3, 35% (30-41) for a Northern Ireland-stringency lockdown with schools closed, and 44% (37-49) for a Wales-stringency lockdown with schools closed. From Oct 1, 2020, to March 31, 2021, a projected COVID-19 epidemic without tiered restrictions or lockdown results in 280 000 (95% projection interval 274 000-287 000) hospital admissions and 58 500 (55 800-61 100) deaths. Tiered restrictions would reduce hospital admissions to 238 000 (231 000-245 000) and deaths to 48 600 (46 400-50 700). From Nov 5, 2020, a 4-week Wales-type lockdown with schools remaining open-similar to the lockdown measures announced in England in November, 2020-was projected to further reduce hospital admissions to 186 000 (179 000-193 000) and deaths to 36 800 (34 900-38 800). Closing schools was projected to further reduce hospital admissions to 157 000 (152 000-163 000) and deaths to 30 300 (29 000-31 900). A projected lockdown of greater than 4 weeks would reduce deaths but would bring diminishing returns in reducing peak pressure on hospital services. An earlier lockdown would have reduced deaths and hospitalisations in the short term, but would lead to a faster resurgence in cases after January, 2021. In a post-hoc analysis, we estimated that the second lockdown in England (Nov 5-Dec 2) reduced Rt by 22% (95% CrI 15-29), rather than the 32% (25-39) reduction estimated for a Wales-stringency lockdown with schools open. Interpretation: Lockdown measures outperform less stringent restrictions in reducing cumulative deaths. We projected that the lockdown policy announced to commence in England on Nov 5, with a similar stringency to the lockdown adopted in Wales, would reduce pressure on the health service and would be well timed to suppress deaths over the winter period, while allowing schools to remain open. Following completion of the analysis, we analysed new data from November, 2020, and found that despite similarities in policy, the second lockdown in England had a smaller impact on behaviour than did the second lockdown in Wales, resulting in more deaths and hospitalisations than we originally projected when focusing on a Wales-stringency scenario for the lockdown. Funding: Horizon 2020, UK Medical Research Council, and the National Institute for Health Research.

The Lancet. Infectious diseases · 109 citationsread the source →

Severity, predictors and clinical correlates of Post-COVID syndrome (PCS) in Germany: A prospective, multi-centre, population-based cohort study.

Background: Post-COVID syndrome (PCS) is an important sequela of COVID-19, characterised by symptom persistence for >3 months, post-acute symptom development, and worsening of pre-existing comorbidities. The causes and public health impact of PCS are still unclear, not least for the lack of efficient means to assess the presence and severity of PCS. Methods: COVIDOM is a population-based cohort study of polymerase chain reaction (PCR) confirmed cases of SARS-CoV-2 infection, recruited through public health authorities in three German regions (Kiel, Berlin, Würzburg) between November 15, 2020 and September 29, 2021. Main inclusion criteria were (i) a PCR confirmed SARS-CoV-2 infection and (ii) a period of at least 6 months between the infection and the visit to the COVIDOM study site. Other inclusion criteria were written informed consent and age ≥18 years. Key exclusion criterion was an acute reinfection with SARS-CoV-2. Study site visits included standardised interviews, in-depth examination, and biomaterial procurement. In sub-cohort Kiel-I, a PCS (severity) score was developed based upon 12 long-term symptom complexes. Two validation sub-cohorts (Würzburg/Berlin, Kiel-II) were used for PCS score replication and identification of clinically meaningful predictors. This study is registered at clinicaltrials.gov (NCT04679584) and at the German Registry for Clinical Studies (DRKS, DRKS00023742). Findings: In Kiel-I (n = 667, 57% women), 90% of participants had received outpatient treatment for acute COVID-19. Neurological ailments (61·5%), fatigue (57·1%), and sleep disturbance (57·0%) were the most frequent persisting symptoms at 6-12 months after infection. Across sub-cohorts (Würzburg/Berlin, n = 316, 52% women; Kiel-II, n = 459, 56% women), higher PCS scores were associated with lower health-related quality of life (EQ-5D-5L-VAS/-index: r = -0·54/ -0·56, all p < 0·0001). Severe, moderate, and mild/no PCS according to the individual participant's PCS score occurred in 18·8%, 48·2%, and 32·9%, respectively, of the Kiel-I sub-cohort. In both validation sub-cohorts, statistically significant predictors of the PCS score included the intensity of acute phase symptoms and the level of personal resilience. Interpretation: PCS severity can be quantified by an easy-to-use symptom-based score reflecting acute phase disease burden and general psychological predisposition. The PCS score thus holds promise to facilitate the clinical diagnosis of PCS, scientific studies of its natural course, and the development of therapeutic interventions. Funding: The COVIDOM study is funded by the Network University Medicine (NUM) as part of the National Pandemic Cohort Network (NAPKON).

EClinicalMedicine · 132 citationsread the source →

Spirituality and mental health

INTRODUCTION All along, the majority position of Psychiatry has been that Psychiatry has nothing to do with religion and spirituality. Religious beliefs and practices have long been thought to have a pathological basis, and psychiatrists over a century have understood them in this light. Religion was considered as a symptom of mental illness. Jean Charcot and Sigmund Freud linked religion with neurosis. DSM3 portrayed religion negatively by suggesting that religious and spiritual experiences are examples of psychopathology. But recent research reports strongly suggest that to many patients, religion and spirituality are resources that help them to cope with the stresses in life, including those of their illness. Many psychiatrists now believe that religion and spirituality are important in the life of their patients. The importance of spirituality in mental health is now widely accepted. As John Turbott[1] puts it, rapprochement between religion and psychiatry is essential for psychiatric practice to be effective. The Royal College of Psychiatrists, London, has a special group on Psychiatry and Spirituality. The American College of Graduate Medical Education mandates in its special requirements for residency training in Psychiatry, that all programs must provide training in religious and spiritual factors that can influence mental health. The World Psychiatric Association recently established a section on psychiatry and religion. Lukoff et al.[2] proposed that the diagnostic entities of religious and psychospiritual problems should be incorporated in DSM4 which has been accepted. DSM4, V 62.89 includes three categories—normal religious and spiritual experiences; religious and spiritual problems leading to mental disturbances; and mental disturbances with a religious and spiritual context. I understand that the Indian Psychiatric Society has formed a task force on spirituality and mental health which is urging the Medical council of India to include taking the spiritual history as part of psychiatric evaluation. Even so the importance of religion and spirituality are not sufficiently recognized by the psychiatric community. Religion does not have a place in most of the psychiatry text books. Only very few psychiatrists make use of religion and spirituality in the therapeutic situation. This paper makes an attempt to bring out the importance of spirituality in mental health. WHAT IS SPIRITUALITY? Spirituality is a globally acknowledged concept. It involves belief and obedience to an all powerful force usually called God, who controls the universe and the destiny of man. It involves the ways in which people fulfill what they hold to be the purpose of their lives, a search for the meaning of life and a sense of connectedness to the universe. The universality of spirituality extends across creed and culture. At the same time, spirituality is very much personal and unique to each person. It is a sacred realm of human experience. Spirituality produces in man qualities such as love, honesty, patience, tolerance, compassion, a sense of detachment, faith, and hope. Of late, there are some reports which suggest that some areas of the brain, mainly the nondominant one, are involved in the appreciation and fulfillment of spiritual values and experiences.[3–5] SPIRITUALITY AND RELIGION Religion is institutionized spirituality. Thus, there are several religions having different sets of beliefs, traditions, and doctrines. They have different types of community-based worship programs. Spirituality is the common factor in all these religions. It is possible that religions can lose their spirituality when they become institutions of oppression instead of agents of goodwill, peace and harmony. They can become divisive instead of unifying. History will tell us that this had happened from time to time. It has been said that more blood has been shed in the cause of religion than any other cause. The medieval holy wars of Europe; the religion-based terrorism and conflicts of modern times are examples. We must remember that the institutions of religion are supposed to help us to practice spirituality in our lives. They need periodical revivals to put spirituality in place. SPIRITUAL DIMENSION IS IMPORTANT IN MENTAL HEALTH Mental health has two dimensions—absence of mental illness and presence of a well-adjusted personality that contributes effectively to the life of the community. Ability to take responsibility for one's own actions, flexibility, high frustration tolerance, acceptance of uncertainty, involvement in activities of social interest, courage to take risks, serenity to accept the things which we cannot change, courage to change the things which we can change, the wisdom to know the difference between the above, acceptance of handicaps, tempered self-control, harmonious relationships to self, others, including Nature and God, are the essential features of mental health. Spirituality is an important aspect of mental health. St. Augustine prayed “O God, thou created us in thy image and our hearts will be restless until they find their rest in Thee.” Though Sigmund Freud looked upon religion as an illusion and neurosis, Carl Jung considered the psyche as a carrier of truth, powerfully rooted in the unconscious mind. Religion is important, directly and indirectly, in the etiology, diagnosis, symptomatology, treatment and prognosis of psychiatric disturbances. Lack of spirituality can interfere with interpersonal relationships, which can contribute to the genesis of psychiatric disturbance. Psychiatric symptoms can have a religious content. For example, the loss of interest in religious activities is a common symptom of depression. Too much and distorted religious practices are common in schizophrenia. It is well recognized that some religious states and experiences are misdiagnosed as symptoms of psychiatric illness. Visions and possession states are examples. The spiritual background of the patient will help in the diagnosis of psychiatric disturbance. They are important in the treatment of psychiatric disturbance because spiritual matters can be profitably incorporated in psychotherapy. Spirituality is important in the prognosis of psychiatric conditions. In the spiritual perspective, a differentiation must be made between cure and healing. Cure is the removal of symptoms. Healing is the healing of the whole person. Adversity often produces maturity. Hence in psychotherapy, the patient must be helped to accept the handicap and transform the handicap to a life of usefulness. SOME SIGNIFICANT CLINICAL AND RESEARCH FINDINGS Recent studies show that religious beliefs and practices are supportive to cope with stresses in life and are beneficial to mental health. Thomas Ashby Wills,[6] Professor of Epidemiology and population health at Albert Einstein College of Medicine developed a scale that determines how important is religion to people. This was administered to 1182 children in New York. It was found that religiosity kept children from smoking, drinking and drug abuse by buffering the impact of life stresses. Gene H. Brody,[7] a research professor of child and family development at the University of Georgia, Athens, found that parents who were more involved in church activities were more likely to have harmonious marital relationships and better parenting skills. That in turn enhanced children's competence, self-regulation, psychosocial adjustment and school performance. Miller et al.[8] made a 10-year follow up study on depressed mothers and their offsprings and reported that maternal religiosity and mother-child concordance in religiosity were protective against depression in the offspring. They also reported that low level of religiosity was associated with substance abuse in the offsprings.[9] J. Scott Tonigan,[10] a research professor of psychiatry at the University of New Mexico, followed up 226 patients of alcohol dependence and reported that spirituality predicts behavior such as honesty and responsibility which in turn promoted alcohol abstinence. Wagner and King[11] conducted a study involving three groups—one group of patients who had psychotic illness, one group of formal care givers, and a third group of informal caregivers. The existential needs were the most important for the patient group, while the other groups considered material needs such as housing and work as more important. Neeleman and King[12] surveyed the psychiatric practices of 231 psychiatrists in London. 73% had no religious affiliation, 28% had belief in God, 61% believed that religion can protect against mental illness, and 48% asked patients about their religious practices. Baetz et al.[13] surveyed 1204 psychiatrists and 157 psychiatric patients in Canada. 54% of psychiatrists believed in God, 47% asked patients regarding their religious beliefs, and 55% consulted clergy for the management of patients. Among the patients, 71% believed in God, and 24% preferred psychiatrists who were religious. In an Australian survey, a large majority of patients with psychiatric illness wanted their therapists to be aware of their spiritual beliefs and needs and believed that their spiritual practices helped them to cope better.[14] Mathai and North[15] constructed a questionnaire, consisting of 5 questions and gave it to 70 parents of children attending child and adolescent mental health clinic. They reported that majority of the parents believed that spiritual concerns were important and that therapists should consider their spiritual beliefs in the management of the problems of the children. In USA, Curlin et al.[16] conducted a study of psychiatrists and compared them with physicians from other specialities in their religious affiliations and found that psychiatrists showed less religious affiliations. Several empirical studies on psychiatrists' religious characteristics have indicated that psychiatrists are significantly less religious than the general population, their patients and other physicians.[17],[18] In a 12-year follow up of all articles appearing in American Journal of Psychiatry and Archives of General Psychiatry, 72% of the religious commitment variables were beneficial to mental health; participation in religious services, social support, prayer and relationship with God were beneficial in 92% of citations.[19] Similar findings were reported in a review of the Journal of Family Practice.[20] In a British epidemiological study, church going and active religion were found to be protective to vulnerability for depression by Brown and Prudo.[21] In a detailed study on suicide in Netherlands, Kerkoff [quoted by Sims[22]] reported that there was a decline in suicidal rate, which was concurrent with a religious revival. A study on the factors in the course and outcome of schizophrenia was conducted in the Department of psychiatry, Christian Medical College, Vellore.. It was a collaborative study among three centers—Vellore, Madras and Lucknow. A two-year and five-year follow up showed that those patients who spent more time in religious activities tended to have a better prognosis.[23],[24] The above reports strongly suggest that religious beliefs and practices of psychiatric patients should be given importance. The sense of hope and spiritual support that patients get by discussing religious matters help them to cope better. They also suggest that the importance of religion and spirituality is not sufficiently recognized by the psychiatric community. Mental health workers must take it seriously since psychiatry cannot afford to ignore the importance of spirituality and religion in psychiatry. Sims[22] gives two case histories which drives home this fact. One is the case of Jim who suffered from Korsakov's psychosis. He was so deteriorated that he mistook his wife for a hat. In the ward, others considered him as desolate individual. But his behavior in the chapel was normal. In absolute concentration and attention, he would partake Holy Communion. He did not forget anything nor did he show any signs of Korsakov's psychosis. The other patient had chronic schizophrenia. He used to hear a voice commanding him to jump out of the window. His simple devout mother had taught him to resist the voice by praying to God. His mind was destroyed, but the capacity for spiritual life was present. Unfortunately, on the final occasion, he was too late to pray and he lost his life. Sims makes a comment, “It is unfortunate that we as psychiatrists can be so crass as to neglect this area of life which is clearly important to many of our patients.” Andresen,[25] in an editorial, has pointed out that our civilization's “loss of soul” may cause psychiatric symptoms such as depression, obsessions, addictions, and violence. She has suggested that it is the responsibility of psychiatrists to remind the medical fraternity the necessity of putting back the soul in medical ethics and the fact that spirituality is of vital importance for the mental health of people. WHAT CAN WE DO? As pointed out earlier, spiritual values and religious practices are important in the lives of our patients. Many of their problems may centre round existential preoccupations. It is therefore important that we incorporate spirituality and religious practices in our treatment protocol. We must propagate the Bio-psycho-socio-spiritual model in our approach in psychiatry. Harold Koening,[26] in his paper Religion and Mental health: what should psychiatrists do?, has made some suggestions in this area. Psychiatric history should be catered to the patients' spiritual orientation and religious practices. When we take psychiatric history, we usually ask for the denomination the patient belongs. We do not try to find out how the patient experiences religion. What does religion and spirituality mean to the patient. The psychiatric history should gather information about patient's religious background and experiences in the past and what role religion plays in coping with life stresses. Has patient had any past negative religious experiences? Has he got spiritual and social support from the congregation which he attends? How active is he in the religious congregation? Some religious beliefs can be in conflict with the proposed treatment. Some religious groups are against any type of treatment. Some religious conflicts and frustrations may be contributing to the present psychiatric problem. Sexual abuse by religious workers, traumatic events which turned the patient away from religious beliefs and activities, unanswered prayers, etc. are examples. There are some questionnaires that can be used to take a history of spirituality and religious experiences.[152728] Discussion with the patient on spiritual matters and religious experiences will strengthen the therapeutic relationship. It can also lead to reversal effect of a personal growth of the therapist. We should respect and support patients' religious beliefs if these help them to cope better or do not adversely affect their mental health. For example, if a patient says that his discipline of fasting and prayer helps him to cope better, then this has to be encouraged. We should also challenge the beliefs that can adversely affect mental health. This has to be done very tactfully. It is better to be neutral till we understand the patients and the issues involved well and a good therapeutic relationship is formed. Patients may wish to discuss with the therapist regarding their subjective experiences and existential needs. We should spend time in listening to them. Partnership with the religious workers is an useful area. Leavy and King[29] in their paper, The devil in the detail: partnership between psychiatry and faith based organizations, brings out the importance of such a partnership. They have reported that in UK, the clergy continue to have a central role in several communities and the utility of their involvement in the care of people with mental health problems is increasing. They have argued the importance of examining the form and parameters of partnership between the mental health team and the faith-based communities. For this partnership to be effective, the mental health workers must be spiritually oriented and the religious workers must be better informed about mental health and illness. As referred to earlier, some religious experiences are often misdiagnosed as symptoms of mental illness and vice versa, some psychiatric symptoms are explained as spiritual experiences. According to Sims,[22] phenomena such as faith, prayer and magic can lend themselves to description and definition using Jasperian phenomenology which can lead to a clear differentiation of normal and pathological religious experiences. This emphasizes the importance of psycho-pastoral partnership. One example of such a partnership is the Bangalore psycho-pastoral association, which runs a very efficient half-way home for psychiatric patients. Recognizing the importance of this, the World Council of Churches has formed an Advisory group on mental health and faith communities, which has been active in the exploration of strategies for an effective partnership between mental health services and faith communities. There can be problems in such a partnership. The religious workers may be reluctant to get involved in secular programs, leaving their spiritual fortress. Some of them can have incorrect ideas about the causes of mental illness, which can interfere with the treatment program. Some others can be against medical treatment. Mental health workers can also be prejudiced against the patients' religious beliefs and practices. As referred to earlier, research findings suggest that majority of psychiatrists do not give importance to the spiritual and religious experiences of patients. According to Neelman and Persaud,[30] this may be due to the following factors. Psychiatrists are by and large less religious than other physicians; psychiatrists often come to know of spirituality through the pathological religious symptoms of patients, which make them prejudiced against spirituality; psychiatrists tend to have a biological approach to mental illness, which ignores spiritual dimension; and psychiatrists may think that religion and spirituality cause dependence and guilt feelings. All these can be minimized with dialogue and periodical orientation programs. As John Turbott[31] puts it, psychiatry as a whole can only benefit if the concepts and vocabulary of religion and spirituality are more widely known and discussed among its practitioners. It is also true that conflicts and problems arise more with religious experiences and not with spirituality Praying with the patient is a controversial area. Many psychiatrists will argue that it is a dangerous ground upon which to tread. If at all it is done, it should be done only after a strong therapeutic relationship is established and only if the patient asks for it. Praying for the patient can be beneficial. Research. Although there is substantial body of literature that describes the connection between mental health and spirituality, we must develop theoretical models to understand their relationship in practice. The statistical findings reported earlier were mainly the results of surveys. High-quality evidence-based research is required to make the clinical applications more objective and effective. There are ample opportunities to do research in this area. Phenomena such as meditation, religious faith, and concepts are all What are their to normal life and psychiatric What are the which influence spiritual experiences? If spirituality is to mental health and if religious beliefs and experiences are important in the life of the psychiatric it is only that we should include religious concepts in psychotherapy. For example, some and can be profitably used to help the patient to cope with life situation. The spiritual concepts are incorporated in the treatment of out of the to spirituality. describes a which is called This is a treatment spiritual values to behavior which was developed and promoted at the University of areas are meaning and purpose and The patient is through to meaning and This with examining the of life such as and the patient to the patient is to the of of and in life. The the patient's that and and The involves a on after examining and one's in life. meaning is by meaning for each This is by and factors life and illness The are of and The use of meditation, and with of beliefs and on symptoms form the of the treatment. When the patient negative is the treatment about each about The are depression and adolescent show that produces

Indian Journal of Psychiatry · editorial or comment · 106 citationsread the source →

PATHOPHYSIOLOGY OF DEPRESSION: DO WE HAVE ANY SOLID EVIDENCE OF INTEREST TO CLINICIANS?

Major depressive disorder (MDD) is a common and costly disorder which is usually associated with severe and persistent symptoms leading to important social role impairment and increased mortality 1,2. It is one of the most important causes of disability worldwide 3. The high rate of inadequate treatment of the disorder remains a serious concern 1. This review is aimed at summarizing the solid evidence on the etiology and pathophysiology of MDD that is likely relevant for clinical psychiatry. Neurobiological findings are regarded as solid when they are consistent and convergent, i.e., they have been confirmed by several studies using the same method and fit into results from studies using different methodological approaches. Family, twin, and adoption studies provide very solid and consistent evidence that MDD is a familial disorder and that this familiality is mostly or entirely due to genetic factors 4. This important finding suggests that parental social behavior and other familial environmental risk factors are not as important in the pathogenesis of MDD as previously assumed and should not be the major focus of the treatment of the disorder. The above-mentioned studies consistently show that the influence of genetic factors is around 30–40% 4. Non-genetic factors, explaining the remaining 60–70% of the variance in susceptibility to MDD, are individual-specific environmental effects (including measurement error effects and gene-environment interactions). These effects are mostly adverse events in childhood and ongoing or recent stress due to interpersonal adversities, including childhood sexual abuse, other lifetime trauma, low social support, marital problems, and divorce 5,6. These results suggest that there is a huge potential in the prevention of MDD by means of psychosocial interventions (e.g., in schools, at workplace). In addition, these results mirror the clinical practice of empirically validated psychotherapies to treat depression 7,8,9, including interpersonal, psychodynamic and cognitive behavioral psychotherapies and cognitive behavioural analysis system of psychotherapy, which all focus directly or indirectly on interpersonal difficulties and skills. This does not exclude the fact that unidentified non-genetic, non-psychosocial risk factors may also play important roles in some patients (e.g., climatic change, medical conditions). Stress sensitivity in depression is partly gender-specific. While men and women are, in general, equally sensitive to the depressogenic effects of stressful life events, their responses vary depending upon the type of stressor. Specifically, men are more likely to have depressive episodes following divorce, separation, and work difficulties, whereas women are more sensitive to events in their proximal social network, such as difficulty getting along with an individual, serious illness, or death 10. These findings point to the importance of gender-sensitive psychosocial approaches in the prevention and treatment of MDD. In contrast to the very solid evidence from epidemiological studies on broad risk factor domains, there is no solid evidence for specific genes and specific gene-by-environment interactions in the pathogenesis of MDD. Genome-wide association studies have indicated that many genes with small effects are involved in complex diseases, increasing the difficulty in identifying such genes 11. While there has been progress in the search for risk genes for several complex diseases despite this methodological problem 12, psychiatric conditions have turned out to be very resistant to robust gene identification. For example, based on a community-based prospective study, it has been proposed that a specific genetic variation in the promoter region of the serotonin transporter (a target of antidepressant drugs) interacts with stressful life events in the pathogenesis of depression 13. Although there is high clinical and neurobiological plausibility of this interaction, a recent meta-analysis yielded no evidence that the serotonin transporter gene alone or in interaction with psychological stress was associated with the risk of depression 14. The limited success of genetic studies of depression has been related to use of current classification schemas including ICD-10 and DSM-IV. These diagnostic manuals are based on clusters of symptoms and characteristics of clinical course that do not necessarily describe homogenous disorders but instead reflect common final pathways of different pathophysiolgical processes 15,16. The clinician should be aware that family history will continue to be the most solid source of information to estimate the genetic risk of MDD. Corticotropin-releasing hormone (CRH) is released from the hypothalamus in response to the perception of psychological stress by cortical brain regions. This hormone induces the secretion of pituitary corticotropin, which stimulates the adrenal gland to release cortisol into the plasma. The physiologic response to stress is partly gender-specific: women show generally greater stress responsiveness than men, which is consistent with the greater incidence of major depression in women 17. Moreover, men show greater cortisol responses to achievement challenges, whereas women show greater cortisol responses to social rejection challenges 18. Although MDD is considered as a stress disorder, most subjects treated for MDD have no evidence of dysfunctions of the hypothalamic-pituitary-adrenal axis (HPA) 19. However, some subjects with MDD do show abnormalities of that axis and of the extrahypothalamic CRH system 20. Altered stress hormone secretion appeared to be most prominent in depressed subjects with a history of childhood trauma 21. Elevated cortisol may act as a mediator between major depression and its physical long-term consequences such as coronary heart disease, type II diabetes, and osteoporosis 22. The importance of HPA axis dysfunction for the efficacy of antidepressants is a matter of debate 23. This axis is regulated through a dual system of mineralocorticoid (MR) and glucocorticoid (GR) receptors. Decreased limbic GR receptor function 24,25 and increased functional activity of the MR system 26 suggest an imbalance in the MR/GR ratio in stress-related conditions such as MDD. Epigenetic regulation of the glucocorticoid receptors has been associated with childhood abuse 27. Such environmental programming of gene expression may represent one possible mechanism that links early life stress to abnormal HPA axis function and increased risk of MDD in adults. While the CRH stimulation test (dex/CRH test) 28 is a sensitive measure of the HPA axis dysfunction in depression, the specificity of this test for MDD is low. However, non-suppression in the dex/CRH test has consistently predicted increased risk for depressive relapse during clinical remission 23. Additionally, the measurement of waking salivary cortisol concentration has been shown to be a simple and sensitive test for HPA axis hyperactivity in depression 29. Hypercortisolemia is almost exclusively found in subjects with severe and psychotic depression, in whom glucocorticoid antagonists may have some therapeutic effect 30. There is convergent evidence for CRH to play a major role in the pathogenesis of certain types of depression. Levels of CRH in the cerebrospinal fluid are elevated in some depressed subjects 31. Post-mortem studies reported an increased number of CRH secreting neurons in limbic brain regions in depression 32, likely reflecting a compensatory response to increased CRH concentrations 33. In addition, CRH produces a number of physiological and behavioral alterations that resemble the symptoms of major depression, including decreased appetite, disrupted sleep, decreased libido, and psychomotor alterations 34. There is also preliminary evidence that CRH1 receptor antagonists reduce symptoms of depression and anxiety 35. “Sickness behavior” as a result of an activation of the inflammatory response system shares many symptoms with depression, including fatigue, anhedonia, psychomotor retardation, and cognitive impairment. Sickness is mediated by pro-inflammatory cytokines such as interleukin-1α, tumor necrosis factor-α, and interleukin-6, which activate the HPA axis and impair the central serotonin system 36. The prevalence of depression as an unwanted effect of recombinant interferons is around 30% 37. In animals, blocking pro-inflammatory cytokine-mediated signaling produces antidepressant-like effects 38. Clinical data suggest that cytokines may play a role in the pathophysiology of a subgroup of depressed subjects, particularly those with comorbid physical conditions 36. The antidepressant enhancing effect of acetylsalicylic acid 39 points to the possible clinical relevance of psychoneuroimmunology in clinical depression research. Taken together, the laboratory tests with the highest potential to be clinically useful in the care of depressed individuals are based on abnormalities of the neuroendocrine and neuroimmune systems. Despite the large amount of basic science data suggesting that the HPA axis is importantly involved in the pathophysiology of depression, the effect of pharmacological modulation of this neuroendocrine system as antidepressant therapy has been disappointing. The link between childhood trauma and a permanently altered physiologic stress system points to the use of specific psychotherapies in the treatment of depressed patients with a history of early life trauma 40. Most of the serotonergic, noradrenergic and dopaminergic neurons are located in midbrain and brainstem nuclei and project to large areas of the entire brain. This anatomy suggests that monoaminergic systems are involved in the regulation of a broad range of brain functions, including mood, attention, reward processing, sleep, appetite, and cognition. Almost every compound that inhibits monoamine reuptake, leading to an increased concentration of monoamines in the synaptic cleft, has been proven to be a clinically effective antidepressant 19. Inhibiting the enzyme monoamine oxidase, which induces an increased availability of monoamines in presynaptic neurons, also has antidepressant effects. These observations led to the pharmacologically most relevant theory of depression, referred to as the monoamine-deficiency hypothesis. The monoamine-deficiency theory posits that the underlying pathophysiological basis of depression is a depletion of the neurotransmitters serotonin, norepinephrine or dopamine in the central nervous system. Serotonin is the most extensively studied neurotransmitter in depression. The most direct evidence for an abnormally reduced function of central serotonergic system comes from studies using tryptophan depletion, which reduces central serotonin synthesis. Such a reduction leads to the development of depressive symptoms in subjects at increased risk of depression (subjects with MDD in full remission, healthy subjects with a family history of depression) 41,42, possibly mediated by increased brain metabolism in the ventromedial prefrontal cortex and subcortical brain regions 42. Experimentally reduced central serotonin has been associated with mood congruent memory bias, altered reward-related behaviors, and disruption of inhibitory affective processing 16, all of which add to the clinical plausibility of the serotonin deficiency hypothesis. There is also evidence for abnormalities of serotonin receptors in depression, with the most solid evidence pointing to the serotonin-1A receptor, which regulates serotonin function. Decreased availability of this receptor has been found in multiple brain areas of patients with MDD 43, although this abnormality is not highly specific for MDD and has been found in patients with panic disorder 44 and temporal lobe epilepsy 45, possibly contributing to the considerable comorbidity among these conditions. However, there is no explanation for the mechanism of serotonin loss in depressed patients, and studies of serotonin metabolites in plasma, urine and cerebrospinal fluid, as well as post-mortem research on the serotonergic system in depression, have yielded inconsistent results. There is preliminary evidence that an increased availability of the brain monoamine oxidase, which metabolizes serotonin, may cause serotonin deficiency 46. In addition, loss-of-function mutations in the gene coding for the brain-specific enzyme tryptophan hydroxylase-2 may explain the loss of serotonin production as a rare risk factor for depression 47. Dysfunction of the central noradrenergic system has been hypothesized to play a role in the pathophysiology of MDD, based upon evidence of decreased norepinephrine metabolism, increased activity of tyrosine hydroxylase, and decreased density of norepinephrine transporter in the locus coeruleus in depressed patients 48. In addition, decreased neuronal counts in the locus coeruleus, increased alpha-2 adrenergic receptor density, and decreased alpha-1 adrenergic receptor density have been found in the brains of depressed suicide victims post-mortem 49. Since there is no method to selectively deplete central norepinephrine and no imaging tool to study the central norepinephrine system, solid evidence for abnormalities of this system in depression is lacking. While the classical theories of the neurobiology of depression mainly focused on serotonin and norepinephrine, there is increasing interest in the role of dopamine 50. Dopamine reuptake inhibitors (e.g., nomifensine) and dopamine receptor agonists (e.g., pramipexole) had antidepressant effects in placebo-controlled studies of MDD 51. In the cerebrospinal fluid and jugular vein plasma, levels of dopamine metabolites were consistently reduced in depression, suggesting decreased dopamine turnover 52. Striatal dopamine transporter binding and dopamine uptake were reduced in MDD, consistent with a reduction in dopamine neurotransmission 53. Degeneration of dopamine projections to the striatum in Parkinson's disease was associated with a major depressive syndrome in about one half of cases, which usually preceded the appearance of motor signs 54. Experimentally reduced dopaminergic transmission into the accumbens has been associated with anhedonic symptoms and performance deficits on a reward processing task in subjects at increased risk of depression 55,56. These findings are consistent with the clinical observation that depressed patients have a blunted reaction to positive reinforcers and an abnormal response to negative feedback 57. Almost all established antidepressants target the monoamine systems 58. However, full and partial resistance to these drugs and their delayed onset of action suggest that dysfunctions of monoaminergic neurotransmitter systems found in MDD represent the downstream effects of other, more primary abnormalities. Despite this limitation, the monoamine-deficiency hypothesis has proved to be the most clinically relevant neurobiological theory of depression. New findings on the role of dopamine in depression emphasize the scientific potential of this theory, and promising reports of antidepressant effects of drugs that modulate the dopaminergic system (e.g., pramipexole, modafinil) in difficult-to-treat depression underline its clinical relevance 51,59. Although many historical attempts to localize mental functions have failed, they have considerably contributed to a modern neuroscientific understanding of mental disorders 60. The development of neuroimaging techniques has opened up the potential to investigate structural and functional abnormalities in living depressed patients. Unfortunately, the diversity of imaging techniques used, the relatively small and heterogeneous study samples studied, and the limited overlap of results across imaging paradigms 61 make it difficult to reliably identify neuronal regions or networks with consistently abnormal structure or function in MDD. Functional imaging studies have provided the most limited overlap of findings. This may be due to methodological limitations and/or the complexity of neurocircuitry involved in MDD. A recent meta-analytic study found the best evidence for abnormal brain activity in MDD in lateral frontal and temporal cortices, insula, and cerebellum. In these brain regions activity was decreased at rest, they showed a relative lack of activation during induction of negative emotions, and an increase in activity following treatment with serotonin reuptake inhibitors. Opposite changes may exist in ventromedial frontal areas, striatum and possibly other subcortical brain regions 61. More solid evidence has been provided by structural imaging and post-mortem studies. A recent meta-analytic study on brain volume abnormalities in MDD revealed relatively large volume reductions in the ventromedial prefrontal cortex, particularly in the left anterior cingulate and in the orbitofrontal cortex. Moderate volume reductions were found in the lateral prefrontal cortex, hippocampus and striatum 62. Post-mortem studies consistently identified a reduction in glia cell density in dorsal, orbital and subgenual prefrontal cortices, as well as in the amygdala 63,64. Overall, functional, structural and post-mortem studies suggest that structural and functional abnormalities in the left subgenual cingulate cortex are the most solid neuroanatomical finding in MDD. Volume reduction in this region was found early in illness and in young adults at high familial risk for MDD 65, suggesting a primary neurobiological abnormality associated with the etiology of the illness. Humans with lesions that include the subgenual prefrontal cortex showed abnormal autonomic responses to social stimuli 66, and rats with left-sided lesions in this region had increased sympathetic arousal and corticosterone responses to restraint stress 67. Most importantly, chronic deep brain stimulation to reduce the potentially elevated activity in the subgenual cingulated cortex produced clinical benefits in patients with treatment-resistant depression 68. In summary, despite the considerable heterogeneity of findings from neuroimaging studies, there is convergent evidence for the presence of abnormalities in the subgenual prefrontal cortex in some patients with MDD. Neuroanatomical research in depression is of great clinical interest, since novel antidepressant treatments such as deep brain stimulation can target specific brain regions. In addition, there are promising leads for neuroimaging findings to predict the likelihood of responses to specific treatments 69. Risk factors for depressive episodes change during the course of the illness. The first depressive episode is usually “reactive”, i.e., triggered by important psychosocial stressors, while subsequent episodes become increasingly “endogenous”, i.e., triggered by minor stressors or occurring spontaneously 70. There is consistent evidence that the volume loss of the hippocampus and other brain regions is related to the duration of depression 71, suggesting that untreated depression leads to hippocampal volume loss, possibly resulting in increased stress sensitivity 72 and increased risk of recurrence 73. Glucocorticoid neurotoxicity, glutamatergic toxicity, decreased neurotrophic factors, and decreased neurogenesis have been proposed as possible mechanisms explaining brain volume loss in depression. There is no solid evidence on of these since there are no imaging to directly and neurotrophic processes in neurotrophic factor has considerable Specifically, studies have shown between and in hippocampal as well as expression of following antidepressant treatment The clinician should be aware of the potentially effect of depression and treat depressed patients as early and as A of studies consistently showed reductions in acid concentrations in the prefrontal and cortex in depression This may reflect stress since psychological stress to presynaptic of prefrontal neurotransmission low concentration may reflect reduction in the density and of In addition, chronic stress may reduce receptor possibly through changes in evidence of the hypothesis of depression the lack of effects of drugs on depressive symptoms and prefrontal concentration in subjects with MDD of evidence suggest a dysfunction of the neurotransmitter system in a of the receptor produced and large antidepressant effects in patients with treatment-resistant MDD inhibitors of release (e.g., antidepressant abnormal levels were found in depressed subjects as by and there is evidence for abnormal signaling in post-mortem Since is the major neurotransmitter involved in almost every brain the of the specific role of in depression (e.g., there are promising leads that the receptor is involved in MDD and are diagnostic for MDD, suggesting regulation in depressed patients. In addition, some depressive symptoms may show psychomotor of of positive and negative and a subgroup of patients with MDD may have a disorder In healthy young subjects, changes in the of the had specific effects on subsequent mood In depressed patients, of can have antidepressant on these abnormalities have been hypothesized to be associated with MDD The association between of the and in cortisol in some subjects with and the effect of antidepressants on of and to the of this hypothesis Despite of the many promising the and genetic of this hypothesis are It remains to be antidepressant effects of such as directly to of on these abnormalities have been hypothesized to be associated with MDD The association between of the and in cortisol in some subjects with and the effect of antidepressants on of and to the of this hypothesis Despite of the many promising the and genetic of this hypothesis are It remains to be antidepressant effects of such as directly to of The and of the neurobiological of depression are in 1. The many theories of depression and the relatively low response rate of all antidepressant treatments a hypothesis of and suggest that depression is a clinically and heterogeneous disorder. This research on of the response to therapeutic interventions using such as neuroimaging and neuroendocrine tests in with for with to stress sensitivity and antidepressant The of of therapeutic will for the development of that has the potential to interventions and to up pathways in the of novel therapeutic approaches.

World Psychiatry · editorial or comment · 607 citationsread the source →

Characteristics, symptomatology and naturalistic treatment in individuals at-risk for bipolar disorders: baseline results in the first 180 help-seeking individuals assessed at the Dresden high-risk project.

Background: Considering results from the early recognition and intervention in psychosis, identification and treatment of individuals with at-risk states for the development of bipolar disorders (BD) could improve the course and severity of illness and prevent long-term consequences. Different approaches to define risk factors and groups have recently been published, data on treatment options are still missing. Methods: Help-seeking persons at the early recognition center in Dresden, Germany, were assessed with a standardized diagnostic procedure including following risk factors for BD: familial risk, increasing mood swings, subsyndromal (hypo)manic symptoms, specific sleep and circadian rhythm disturbances, anxiety/fearfulness, affective disorder, decreased psychosocial functioning, increasing periodic substance use, and attention-deficit/hyperactivity disorder. Based on symptomatology and current and/or life-time psychiatric diagnosis, subjects with an at-risk state were offered individual treatment options. Results: Out of 180 referred and screened persons, 29 (16%) met criteria for at-risk state for BD. Altogether, 27 (93%) at-risk individuals fulfilled criteria for a current and/or life-time mental illness other than BD; 14 (48%) had received pharmacological and/or psychotherapeutic treatment in the past. Treatments recommended included psychoeducation (100%), psychotherapy alone (62%), pharmacotherapy alone (17%), and psychotherapy+pharmacotherapy (14%). Conclusions: To identify at-risk states for BD, a multifactorial approach including all known risk markers should be used. As most at-risk patients meet criteria for other mental disorders, the short- and long-term impact of different treatment strategies on symptomatic, functional and diagnostic outcomes requires detailed investigation. Limitations: Small sample size of at-risk individuals, lack of sufficient prospective data and control groups.

Journal of affective disorders · 20 citationsread the source →

The phenomenon of 'chronic Lyme'; an observational study.

Purposes: To chart clinical, laboratory, and psychometric profiles in patients who attribute their complaints to chronic Lyme disease. Methods: We assessed the patients by clinical examination, laboratory tests, and questionnaires measuring fatigue, depression, anxiety, health-related quality of life, hypochondriasis, and illness perceptions. Results: We found no evidence of ongoing Borrelia burgdorferi (Bb) infection in any of the 29 included patients using current diagnostic guidelines and an extended array of tests. Eight (28%) had other well-defined illnesses. Twenty-one (72%) had symptoms of unknown cause, of those six met the suggested criteria for post-Lyme disease syndrome. Fourteen (48%) had presence of anti-Bb antibodies. The patients had more fatigue and poorer health-related quality of life as compared to normative data, but were not more depressed, anxious, or hypochondriacal. Their beliefs about the illness were characterized by negative expectations. Conclusion: Our patients, who all attributed their symptoms to chronic Lyme disease, were heterogeneous. None had evidences of persistent Bb infection, but whether current diagnostic criteria are functional in patients with longstanding complaints is controversial. Other well-defined illnesses or sequelae from earlier Lyme disease were probable as main explanatory factor in some cases. The patients were not more depressed, anxious, or hypochondriacal than the normal population, but they had poorer health-related quality of life, more fatigue, and negative expectations about their illness.

European journal of neurology · 11 citationsread the source →

Prediction and prevention of schizophrenia: what has been achieved and where to go next?

Since the traditional clinical paradigm has been replaced by the modern molecular one, medicine set off into new directions. “Prediction”, “prevention” and “personalization” are the programmatic key words of this new approach. Like other medical disciplines, psychiatry has broadened its focus from diagnosis and treatment to the detection and estimation of the risk of disease development, the prediction of its onset and strategies to avoid its manifestation 1,2,3,4. Although treatment of schizophrenia has greatly advanced over the last decades, a significant number of patients continue to take an unfavorable chronic course 5,6. This makes schizophrenia the leading cause for permanent occupational disability among people under 40 years of age in Germany 7, and the 8th most common cause for disability adjusted life years (DALYs) lost among the 15 to 34-year olds worldwide 8, despite its low prevalence. Moreover, schizophrenia involves tremendous direct and indirect societal costs 9 and a huge burden on patients and their families 8,10. It is becoming increasingly clear that schizophrenia is a complex disorder with polygenic heredity and that its pathogenesis is greatly influenced by interactions between different genes and between genes and environment. Associations to variants of the genes for dysbindin and neuregulin-1, the genetic locus G72 and the DAOA (D-amino acid oxidase activator) gene have now been repeatedly confirmed. As with all other complex diseases, research is focusing now on characterizing the polygenetic predisposition and clarifying its influence on the development of the phenotype 11. Research methods range from molecular genetics via proteome research to cell biology, neurophysiology, brain structural and functional imaging and neuropsychology. With all these methods, several indicators for an increased risk of schizophrenia have been identified. However, the currently recognized neurobiological risk factors are not sufficiently predictive to allow the development and application of “selective” prevention measures targeting asymptomatic persons at risk. For neuro-psychological risk factors, this has just become evident in the large-scale attempt of the North American Prodrome Longitudinal Study (NAPLS) group to improve their multivariate model by integrating the examined neurocognitive variables 12. There are also established environmental risk factors for schizophrenia, such as pregnancy or birth complications, growing up in a large city, IQ low but normal and drug consumption. However, with odds ratios around 2, each of these factors appears to increase the lifetime risk of the disease only slightly 13. Thus, the currently known risk factors, either alone or taken together, cannot be used for prediction and prevention without knowledge of the complete predispositional basis and the gene-gene and gene-environment interactions, which are probably numerous. In view of this situation, it may be argued that the current efforts towards prediction and prevention are still premature and that further progress of etiological research is needed. However, a different perspective has emerged from the work of the centers for early recognition and prevention, established first in Melbourne, Australia and in Cologne, Germany in the mid 1990s, and later on in many other places around the world. This resulted from retrospective research of the early course of psychosis, in which the pathophysiologically active disturbances in brain development extend beyond early abnormalities in behavior into psychopathologically definable early risk and ultra high risk (UHR) symptoms, depending on the individual combination of stressors and resilience factors. First episode psychosis (FEP) research has shown that the outbreak of the disease is preceded in about 70% to nearly 100% of cases by an initial prodrome, which lasts for an average of five to six years. Even in highly developed health care systems, an average of one year thereafter elapses from the first manifestation of psychotic positive symptoms to the initiation of adequate treatment 14,15. The period over which the FEP remains untreated (duration of untreated psychosis, DUP) correlates with: delayed and incomplete remission of the symptoms; necessity of more protracted treatment and greater risk of relapse; lower compliance, greater burden on the family, and a higher level of “expressed emotion”; increased risk of depression and suicide; greater impact on the individual's employment or education; increased drug abuse and delinquent behavior; markedly increased costs of treatment 16. These correlations have recently been confirmed by a meta-analysis 17, with coefficients ranging from 0.285 to 0.434 (95% CI). This does not only provide strong arguments in favor of treating the FEP as early as possible, but has also led to a systematic effort to decrease the incidence of psychosis through indicated prevention. Two important studies concerning the early stage prior to the conversion to FEP have demonstrated that the earliest and most common symptoms, which generally dominate during the prodrome, are unspecific and cannot be distinguished from impairment in mood, drive, contact, and concentration of depressive episodes. These are the Age-Beginning-Course (ABC) study of schizophrenia, a retrospective study with optimized methods 14, and the Cologne Early Recognition (CER) Study, a long-term prospective study with an average follow-up period just below 10 years 18. These studies also found striking cognitive impairments in the form of self-experienced disturbances in thought, speech, and perception processes. This subgroup of so-called basic symptoms, which were found in more than a quarter of patients, had high specificity and a high positive predictive power, accompanied by only low rates of false positive predictions 19,20,21. Basic symptoms were first operationalized in the Bonn Scale for the Assessment of Basic Symptoms (BSABS). Shorter versions of the scale for adults and for children and adolescents — the Schizophrenia Proneness Instrument, Adult version (SPI-A) and the Schizophrenia Proneness Instrument, Child and Youth version (SPI-CY) — were later developed from dimensional analyses 22,23,24. While the BSABS only allows an assessment of the current state, the SPI-A and the SPI-CY also allow severity ratings according to the maximum frequency of occurrence within the past 3 months. In the CER study, 385 patients who were presumably in the prodromal phase of schizophrenia were followed up for an average of 9.6 (±7.6) years past baseline. Twenty percent of the initial criterion-positive cases (1 of 66 basic symptoms) who agreed to be followed up developed schizophrenia after 12 months, a further 17% after 24 months, a further 13% after 36 months, and finally a total of 70% after an average of 4.5 years. Thus, only 30% did not convert to schizophrenia. The overall presence/absence of at least one basic symptom correctly predicted presence/absence of a subsequent transition to schizophrenia in 78.1% of cases. From further analyses, two partially overlapping basic symptom criteria for defining at risk mental states (ARMS) for psychosis, primarily schizophrenia, were developed (Table 1). The first criterion, which consists of ten cognitive-perceptive basic symptoms and is abbreviated as COPER, was based on findings concerning the predictive accuracy of individual basic symptoms 18,25. The second was based on a methodological re-analysis of the same data set, in which a cluster of nine cognitive basic symptoms had repeatedly been selected as the most predictive. This cluster was called “cognitive disturbances” (COGDIS). In terms of general predictive accuracy, the two criteria slightly differed in the CER study, as COGDIS tended to be more conservative than COPER, i.e. to perform better in ruling in subsequent schizophrenia at the cost of performing worse in ruling it out. The transition rate throughout the average follow-up period of roughly 10 years was 65% for COPER and 79% for COGDIS, with the majority of transitions occurring within the first 3 years past baseline. In a second prospective study 26, conducted with the SPI-A and with a systematic follow-up of 24 months, 38% of the initially included 146 at-risk subjects developed a frank psychosis, mainly schizophrenia, within 12.3 (±10.4) months on average (1–48; median=9) according to COPER. Thus, the positive results of the CER study were confirmed. Again, COGDIS appeared to be more specific but less sensitive than COPER. As a consequence of these findings, predictive basic symptoms have been established as a set of criteria for risk assessment in international research on the early recognition of psychosis. In particular, the German Research Network on Schizophrenia used these symptoms, together with a combined criterion of functional deterioration and biological risk, in defining an “early at-risk of psychosis state” (ERPS), thereby suggesting a clinical risk staging model (Figure 1). Early and late initial prodromal state: a clinical staging approach The positive symptoms typical of schizophrenia — such as delusions, hallucinations or formal thought disorders — often first appear in an attenuated or transient form during the initial prodromal phase. These symptoms provide a valid prediction of conversion into FEP, particularly in the short term. Warning signs of this sort have been used as ultra-high risk (UHR) criteria 27,28. Notwithstanding their differences across studies, these criteria are generally composed of three alternative elements: attenuated positive symptoms (APS), brief limited intermittent psychotic symptoms (BLIPS), or a combination of one or more risk factors (always including genetic risk) and functional decline within a certain recent period. For the ascertainment of the UHR criteria, the Melbourne group gradually developed a specific instrument, the Comprehensive Assessment of At Risk Mental States (CAARMS) 29. Based on the Australian definition of the UHR criteria, the Structured Interview for Prodromal Syndromes (SIPS), the Scale for Prodromal Syndromes (SOPS) and, subsequently, the Criteria of Prodromal Syndromes (COPS) were developed 30,31. Different UHR-related approaches to an early detection of FEP, particularly schizophrenia, were developed by the Hillside Recognition and Prevention (RAP) program in New York 32 and the Basel Früherkennung von Psychosen (FEPSY) study 33. There have been at least 15 prediction studies using UHR criteria, some of which with large samples 34,35,36,37,38,39,40,41. The 12-month rates of transition into FEP published so far range between approximately 13% and 50%. A substantial variance is even observed with comparable observation periods in the same center 34,35. Yet, as the annual incidence for all forms of psychosis in the general population is only about 0.034% 42, even the lowest conversion rates still indicate a dramatic increase in the relative risk of illness, at least in the help-seeking samples of specialized centers. Table 2 depicts the predictive accuracy measures published so far, with the last five listed studies representing secondary predictor analyses of samples meeting at risk criteria. As a result, in the German Research Network on Schizophrenia, the UHR approach was combined with the basic symptom approach and applied in a slightly modified form for the definition of “late at-risk of psychosis state” (LRPS) (Figure 1). This clinical staging model, which suggests a syndromal sequence for the development of FEP progressing from unspecific prodromal symptoms to predictive basic symptoms, and then to APS, to BLIPS and to full-blown psychotic symptoms, was recently strongly supported 15. Universal or selective prevention measures target healthy population groups or clinically still healthy risk carriers, respectively 43. Indicated prevention, instead, targets individuals with basic symptoms and UHR symptoms. Even at the early stages when these individuals seek advice and help at the early recognition and prevention centers, they must be regarded as ill and in need of treatment. Furthermore, the impending deterioration of psychosocial performance in schizophrenia often already occurs in the initial prodromal phase, even prior to the conversion into FEP 14,15. These clinical and psychosocial impairments justify defining the interventions in EPRS and LPRS as indicated prevention, pursuing the following three objectives: a) improvement in the current burden of prodromal symptoms; b) avoidance or perhaps delay in the development of psychosocial handicap; c) prevention of or at least delay or attenuation of psychosis. Five international intervention studies have attempted to find out whether or to what extent these three objectives can be reached 44,45,46,47,48,49,50,51 (Table 3). The preventive measures used were either cognitive behavioral therapy (CBT), adapted to the requirements of the persons at risk, or atypical antipsychotics (risperidone, olanzapine, and amisulpride). These were randomized controlled studies, but there were problems with the blinding condition in the two CBT interventions. This and other methodological shortcomings currently limit conclusions and have encouraged the research groups working in this area to set up new, optimized intervention studies. For example, the protocol of the ongoing parallel group PREVENT study includes careful comparative analyses and superiority and inferiority tests of the psychological and pharmacological treatments 52. A staging of risk, thereby implying a temporal dimension, was considered for the first time in the two intervention studies of the German Research Network on Schizophrenia. One of these studies covered ERPS and only offered CBT as a preventive measure 49,50. The other study was designed for LRPS and used only preventive treatment with amisul-pride 51. When the symptom development in the initial prodromal state follows the sequence shown in Figure 1, it would be beneficial for scientific and especially ethical reasons to focus on psychological interventions in ERPS, which are well tolerated and highly accepted. As soon as the first attenuated or transient psychotic symptoms occur, it seems justifiable to apply well tolerated antipsychotics with few side effects. This differential prevention strategy is now pursued in all German early recognition centers and is also increasingly gaining support in other countries. Another pharmacological option is aripiprazole, tested in a pilot study in UHR states 53. Its possible preventive effects are currently being analyzed in the PREVENT study. Antidepressants were used in a naturalistic, non-randomized observational study of an adolescent sample employing only the APS criterion for inclusion, but, for methodological reasons, this study does not allow any conclusion about differential preventive effects of these medications 54. A critical evaluation of the achievements over the past 15 years through continuous efforts to enhance prediction and prevention of psychoses, particularly of schizophrenia, reveals quite impressive results. However, the results achieved thus far need to be evaluated in the light of the ambitious, initially mentioned objectives of modern predictive and preventive medicine. Once predictive basic symptoms and UHR symptoms have occurred, the underlying pathophysiological process might have already progressed. For such a complex disease with a long-term course and a pre-dispositional basis, this kind of risk identification and risk-oriented prevention may possibly come too late. A more substantial reduction in incidence could be reached with selective and universal prevention measures. Therefore, symptom-based prediction and prevention need to be further developed into the direction of selective prevention for symptom-free risk carriers. In the future, it is necessary to strive for: a) an improvement of risk enrichment with the inclusion of biological risk factors; b) a stronger individualization of the risk estimation by stratification; c) the inclusion of sub-psychotic mental states, as cross-sectionally by current at risk criteria, in the the application of prevention strategies more with the of the the initial prodromal phase for as as then most of the follow-up periods shown in Table 2 are not to the transition A significant number of later may be as and, the predictive of the risk may be 12. Therefore, the first and most important is to out new, optimized large-scale studies with follow-up periods the of the initial prodromal phase, as in the CER study 18. The risk enrichment can also be advanced through the inclusion of following the of recent research on the prediction of through the cognitive impairment This condition a risk for with a conversion rate comparable to the risk for the patients certain imaging and the predictive risk enrichment may be possible for using brain but also impairments of and which are with the psychosis risk and are more and in cases with a later transition to schizophrenia and other new large-scale studies with sufficiently observation periods could whether the risk enrichment can be achieved by of such The of this strategy is on the progress of research on biological and environmental risk factors and their interactions, as is currently attempted in the Network of schizophrenia study In other medical disciplines, such as or a risk which does not in a of is using for multivariate clinical staging by risk In the of study, this approach was into psychosis prediction research for the first time A clinical model was developed based on a including six variables positive disturbances Assessment of in the past and years of Based on the individual a multivariate for further the risk of transition to psychosis into risk was each a increased relative risk to the general with each This model was argued to improve the prediction of psychosis by a of the individual risk in terms of and a more risk estimation or clinical staging of risk, in studies, could the development of risk adapted inclusion criteria for randomized preventive In the first application of this approach in the only clinical and variables were It remains to be whether a model including or environmental variables would increase the predictive accuracy even In studies have to whether such can also be applied to the prediction of psychosis within different time The currently ongoing of the has a about the inclusion of a risk for psychosis in to prevention initially argued this and to the that the application of as criteria could that the high rate of predictions in would be to increase up to in general This is and prior to whether to the in the of the The on the predictive of at risk criteria, thereby the persons meeting at risk criteria already from mental and functional for which they seek Moreover, they psychological and cognitive with and functional the majority of help-seeking at risk persons general criteria for mental disorder a clinically significant behavioral or psychological with disability and have to be considered as i.e. as people with the need and to be these in there are reasons for the inclusion of a clinical in the as by current at risk criteria, not as a prodromal risk for first psychosis, but as an to medical the of such an diagnosis would have the of the by the current mental state to a and Although an increased risk of psychosis would continue to be a of such a the psychological and medical focus would be from an to and At this current state of the criteria would be the for the inclusion of this A for the and of a new of international and studies would be with this inclusion in and later on also in A new prevention approach is by the of and studies a of the onset of psychosis the with the first results are for and The transition rate was lower in an group of UHR adolescents than in a group and this was at a an was evaluated in 10 patients in an pilot and a significant improvement in different was In an study, time was in an UHR group with as with a group suggesting a of This was the first study imaging data on effects in individuals at risk. The preventive of is currently in the process of in the Australian Prodrome study With the of schizophrenia is the first mental disorder to which the prediction and prevention program of modern medicine has been The results are and justify the that in the years to come it be possible to provide preventive strategies to the individual risk of of each In to a reduction in risk assessment has to be by neurobiological and psychosocial risk factors, and indicated prevention has to be further developed towards selective prevention. This a new of large sample studies for prediction as well as prevention, with observation In these studies, of risk selected to predictive must be psychological and pharmacological interventions need to be on a long-term basis, more prevention strategies have to be In to be to and such studies, it would be to mental states, as by the currently used risk symptoms, in the of the

World Psychiatry · 127 citationsread the source →

A social neuroscience perspective on clinical empathy

Clinical empathy is an important element of quality health care. Empathic communication is associated with improved patient satisfaction, increased adherence to treatment, and fewer malpractice complaints 1. Patients' perceptions of their physicians' empathy are positively related to more favorable health outcomes 2-4. In addition to improving patient outcomes, clinical empathy is associated with increased overall well-being for the physician 5. High levels of practitioner empathy have been associated with decreased burnout, personal distress, depression and anxiety, along with increased life satisfaction and psychological well-being 6, 7. Despite increasing appreciation of the value of empathy, medical educators continue to struggle with how best to educate students and residents on empathy maintenance. There have been several promising creative approaches that have shown demonstrable short-term success 8. However, there is a lack of evidence for enduring success, that is, for interventions during medical education that will enable physicians to sustain empathy throughout their careers. A more comprehensive and precise understanding of the subcomponents of empathy and how they are influenced by stress and anxiety is needed in order to design targeted interventions. Empathy is difficult to define, and an operational definition remains elusive. In medicine, empathy has often been conceptualized as consisting of two primary features: cognitive empathy, defined as the ability to recognize and understand another's experience, to communicate and confirm that understanding with the other person, and to take effective action to then act appropriately in a helpful manner 9, and affective empathy, defined as emotional resonance with the patient 10. Cognitive empathy has been singled out as beneficial in the clinical relationship, while affective empathy has been viewed as interfering with the physician's ability to make effective diagnoses and facilitate better outcomes. This has resulted in the teaching and practice of “detached concern”, a process where physicians establish a certain emotional distance from their patients in order to maintain objectivity and limit exposure to the negative emotions routinely experienced by those patients 11. However, recent research has demonstrated that the underlying rationale for implementing a “detached concern” approach is no longer tenable. First, affective engagement contributes to empathy, improving cognitive accuracy as well as affective understanding 12. Second, patients respond differently to emotionally engaged physicians. Patients who perceive their physicians as emotionally attuned or genuinely concerned disclose more, are more adherent to treatment, and show greater agency in addressing serious health problems such as cancer 11. Furthermore, there is now convincing empirical evidence that cognitive and affective aspects interact in the experience of empathy 13. Finally, the primary motivation behind the “detached concern” approach, that emotional connection will necessarily lead individuals into emotional turmoil, is not supported by the literature 14. Despite the clear importance of empathy in clinical settings, many physicians experience difficulty empathizing with their patients. For instance, a study which coded interviews between physicians and lung cancer patients found that, out of 384 empathic opportunities – defined as patients' statements including an explicit description of emotion or patients' statements or clues that indicated an underlying emotion – physicians responded empathically to only 39 (10%), most often reacting with little emotional support and shifting to biomedical questions and statements 15. Using patient-physician interaction videos where students are taught to identify and code these types of empathic opportunities, as well as what would be appropriate empathic responses, could help them more effectively address those opportunities. Additionally, sustaining empathy during distressing moments begins with doctors learning to take their own emotional temperatures, so that they can notice when they are anxious and take a deep breath or count to ten before responding to the patient. Both implementing mindfulness skills 16 and learning to return focus on the patient by becoming curious about what the patient is most concerned about at that moment can help physicians maintain empathy 11. Intensive training in mindful communication has been shown to reduce psychological distress and burnout, and increase empathy 17. The vast majority of individuals have the capacity for empathy, and research suggests that medical students start school with similar or higher levels of empathy compared to an age-matched control group 18. However, empathy significantly declines over the course of medical school 10. The precise underlying causes of this decline are not well understood, and multiple factors likely play a role. The decrease has been attributed to a curriculum that promotes the objectification of the patient 19, increasing workload, mistreatment by supervisors, and lack of emotional support 6, 20. High levels of burnout, personal distress, depression and anxiety have also been found to contribute to the erosion of empathy in medical school 7, 20. Notably, the decline in empathy is not consistent across students. A longitudinal study of 446 medical students found two distinct groups, with 70% showing a significant decline on the Jefferson Scale of Physician Empathy, and 30% seeming to have protective factors that neutralize the erosion of empathy 10. This study demonstrated that individuals in patient oriented specialties showed less decline in empathy than those in technology oriented specialties, and suggested that students with individual traits that protect against empathy erosion self-select into the more patient focused specialties 10. This could be the case, or it could be that training for patient focused areas places more emphasis on skills such as listening to the patient and how to counteract objectification of the patient, important to maintaining empathy in a patient-physician interaction. Additionally, greater perceived social support from faculty and greater satisfaction with the learning quality of the environment have been associated with increased resilience to burnout, and high levels of stress and fatigue have been associated with decreased resilience to burnout 21. As increased burnout has previously been associated with decreased empathy in medical students 22, it is possible that these protective factors might also contribute to maintaining empathy. Empathy is a natural socio-emotional competency that has evolved with the mammalian brain to form and maintain social bonds, and which encompasses different components 13. Affective sharing, the first element of empathy to appear during ontogeny, refers to the unconscious sharing of the affective state of another, which can be assessed by measures of concordance of skin conductance (an index of autonomic arousal) between two individuals 23. Empathic understanding entails the conscious awareness of the emotional state of another person. Empathic concern refers to a motivation to care for someone in need. Successful emotion regulation enables the control of emotion, drive and motivation in the service of adaptive behavior. Even though these components are intertwined and not independent of one another, it is helpful to consider them separately, as each contributes to various aspects of the experience of empathy, and could be the target of specific interventions to promote clinical empathy in medical students 24. Recent work in social neuroscience using functional neuroimaging demonstrates that the affective, cognitive and regulatory components of empathy involve interacting neural circuits 25. Empathic arousal is mediated by strong bidirectional connections between the brainstem, amygdala and sensory cortices, as well as connections with the hypothalamus, insula and somatosensory cortex 13, 24. The cognitive aspects of empathy, such as emotion understanding and emotion regulation, are closely related to processes involved in perspective taking, self-regulation, and executive attention subserved by the medial prefrontal cortex, dorsolateral prefrontal cortex and temporo-parietal junction. Finally, the ability to feel concern and care for others has deep evolutionary roots that likely evolved in the context of parental care 26. Its neural underpinnings are found in subcortical neural systems similar to those known to regulate maternal behavior, especially the hypothalamus and orbitofrontal cortex 27. These components differently contribute to the experience of clinical empathy. Affective sharing may act as a gain antecedent to empathic understanding, while cognitive components are important for representing the mental states of self and other, necessary to make decisions in a medical context 24. Importantly, the type of emotion regulation an individual employs largely determines whether cognitive resources are drained or primed 28. Specifically, research shows that a detached perspective can quickly dampen emotional reactions or filter out emotional information. This can be adaptive to a surgeon while operating on his anesthetized patient, but maladaptive when the same physician interacts with his patient after the surgery 28. This example illustrates the flexibility of emotion regulation in clinical settings, depending on both the physician's goals and the patient's needs. The perception of pain in others acts as an empathic signal, alerting individuals that another person is at risk, attracting their attention and motivating social behaviors. The neural response to the pain and distress of others, a situation familiar to physicians, has been used in social neuroscience research as a window into the neurobiological underpinnings of empathy. Several regions involved in the experience of physical pain, including the anterior cingulate cortex, insula, periaqueductal gray, orbitofrontal cortex and amygdala, are activated by the perception or even the imagination of another individual in pain 29. Importantly, the pattern of neural response is highly flexible and can be modulated by a number of contextual, cognitive, social and interpersonal factors 25. In the context of medicine, two neuroimaging experiments examined the neurophysiological response to the perception of pain in physicians 30, 31. Physicians as well as matched non-physician controls underwent functional magnetic resonance imaging while watching videos of needles being inserted into another person's body parts (face, hands and feet), as well as videos of the same areas being touched by a cotton bud 30. Physicians showed significantly less activation in brain areas involved in empathy for pain (anterior cingulate cortex, insula) than did non-physicians. In addition, physicians showed significantly greater activation in areas involved in executive control, self-regulation, and mental states understanding. These findings suggest less empathic arousal and greater cognitive regulation of an emotional response among the physicians, and indicate that physicians' down-regulation of the pain response dampens their negative arousal to the pain of others. This may have beneficial consequences by freeing up cognitive resources necessary for being of assistance and perhaps even for expressing empathic concern. These results may also inform individual differences in empathic decline and professional distress. Meta-analyses show that clinicians' distress is a key determinant of empathy decline 6. Medical students who are most vulnerable to professional distress, which may lead to emotional exhaustion, detachment and a low sense of accomplishment, may be those who have difficulties regulating their negative emotions. On the other hand, students with overly suppressed pain responses and insufficient negative arousal will also have problems with empathy. Some modicum empathic arousal (or affective sharing) may be necessary to help physicians attune to and empathically understand patients' emotions. A positive emotional reappraisal requires emotional content from the patient to be reinterpreted, molding potentially important information once it is available 28. Empathic disposition varies across individuals, and these differences are likely in part accounted for by interactions between an individual's life history, psychological traits and genetic makeup. Attachment is one construct, first proposed by Bowlby 32, which appears to reside at the interface of all three of these determinants. Attachment theory offers a compelling framework for understanding one's capacity to connect with others and develop supportive relationships as coping resources, and predicts individual differences in empathy 33. Security of attachment correlates with the individual degree of empathy and successful emotion regulation, and is inversely related to pain report and emotional distress 34. Empirical research also indicates that attachment security provides a foundation for empathic concern and caregiving 35. Importantly, these attachment styles are relatively stable across the lifespan. In recent years, a great deal of work has begun to reveal some of the underlying neuroanatomical and neurochemical foundations of attachment-related processes and the variance in such attributes both between and within species 36. Such research has identified a number of neuropeptides that are clearly involved in an array of attachment-related social behaviors, including opioids, vasopressin and oxytocin. Oxytocin, for example, has been demonstrated to play a central role in the initiation of maternal behaviors, social recognition and pair bonding in rodents 37. Studies in humans have demonstrated that oxytocin infusion can modulate a number of attachment-related behaviors, including trust, generosity, empathic concern, and empathic accuracy 38. Oxytocin administration selectively reduces emotional arousal to threatening social images 39 and differentially modulates visual attention toward social signals of positive approach 40. Moreover, it appears that individuals lacking high quality social connections show significantly reduced responses to oxytocin administration 39, which may reflect reduced receptor sensitivity. Research into the influence of genetic variation within the oxytocin receptor has provided converging evidence of the role that oxytocin plays in human social behavior. Polymorphisms within the oxytocin receptor have been shown to be related to affiliative behavior, behavioral and dispositional empathy, and perceived social connectedness 41. Similarly, genetic variation in the oxytocin receptor is related to decreased neuroendocrine and autonomic reactivity to social stress and interacts with perceived social support to dampen physiological reactivity to social-evaluative threat 41. Importantly, this does not suggest that empathy-related behaviors are genetically determined. Particular alleles in the oxytocin receptor system (or vasopressin or opioid systems) previously considered “vulnerability genes” can actually be viewed as “plasticity genes” in that they allow some individuals to be more sensitive to the social environment in general 42. This is consistent with the observation of large individual differences in what can be viewed as a “biological sensitivity to context”, in which people are especially interpersonally adept in socially supportive environments and especially anxious and withdrawn in noxious environments 43. A meta-analysis of studies that evaluated various contextual influences on patient outcomes found that physicians who adopted a reassuring warm and friendly approach were more effective than those employing detached concern 44. Empathic medical care may provide patients with a sense of personal connection and perceived control over their health that results in more effective coping strategies, influencing health outcomes through chronic modulation of physiological stress responses. In fact, a quarter century of research in neuroendocrinology and stress physiology has clearly demonstrated that the perception of social support and stressor controllability can have profound influences on the hormonal, cardiovascular and immunological response to a broad array of physiological responses in both humans and non-human animal models 45. Indeed, perceived controllability over a stressor is associated with prefrontal cortex mediated regulation of limbic (amygdala and hypothalamus) and brainstem (dorsal raphe nucleus) structures associated with neuroendocrine and autonomic nervous system reactivity 45. This provides a direct pathway through which the perception of one's ability to control aspects of his/her disease is capable of regulating physiological processes ranging from glucose metabolism and blood pressure to immunomodulation and neurogenesis 46. Physicians routinely present information to their patients capable of generating substantial physiological stress responses. In many such cases, the physician-patient relationship represents the front line in the battle against disease, as it has the potential to shape the endogenous responses to illness-related stress that, in some cases, can have effects similar to pharmacological interventions 3. Empathic concern, as opposed to detached concern, allows physicians to better understand their patients and modify their approach to fit the individuals they are attempting to treat. Given the past quarter century of work showing that quality emotional connection has comparable influences on health outcomes as obesity and hypertension 47, it is clear that empathic approaches are needed for patient care. The current view of empathy in clinical practice is limited and focused primarily on self-reports of physicians, with little understanding of the mechanisms which contribute to declining empathy during medical school and a lack of empathy generally within the medical field. A better scientific understanding of the connections between the mechanisms involved in interpersonal sensitivity, empathy, and care-giving behavior is needed to help physicians maintain high levels of empathy in clinical practice while limiting burnout and personal distress 48. This understanding should be incorporated into research on the organizational and contextual factors that shape medical professionalization. It is now possible to bring to the study of clinical empathy a risk-vulnerability approach that promises to be both more precise and more comprehensive than previous research. This approach will increase our capacity to design better institutions and educational interventions to support empathy within clinical practice and to protect against its decline. Some interventions to improve empathy and communication between physicians and patients have already shown positive effects on both physicians' professional satisfaction and well-being. There is a need, however, for dedicated research to respond to the vital call for empathy enhancement in medicine with programs using social neuroscience-based knowledge. The writing of this paper was supported by grants from the John Templeton Foundation (The Science of Philanthropy Initiative and Wisdom Research at the University of Chicago) and from National Institutes of Health (R01MH087525; R01MH084934) to J. Decety.

World Psychiatry · 97 citationsread the source →

Lewy body dementia: caregiver burden and unmet needs.

Lewy body dementia (LBD) is a common cause of dementia but to date, little is known about caregiver burden. The Lewy Body Dementia Association (www.LBDA.org) conducted a web-based survey of 962 caregivers (mean age 56 y; 88% women). The most common initial symptoms were cognitive (48%), motor (39%), or both (13%). Caregivers expressed concerns about fear of future (77%), feeling stressed (54%), loss of social life (52%), and uncertainty about what to do next (50%). Caregivers reported moderate-to-severe burden; 80% felt the people around them did not understand their burden and 54% reported feelings of isolation with spousal caregivers reporting more burden than nonspousal caregivers. Only 29% hired in-home assistance, whereas less than 40% used respite or adult day care, geriatric case managers, or attended a support group meeting. Lack of service utilization occurred despite two-thirds of caregivers reporting medical crises requiring emergency services, psychiatric care, or law enforcement. Caregivers reported preferences for web-based information, directories of LBD expert providers, information on LBD research, and location of local support groups. These findings highlight significant unmet needs for LBD caregivers and provide targets for intervention to reduce caregiver burden. Community resources such as the Lewy Body Dementia Association may serve this end, while also providing practical information and support for caregivers.

Alzheimer disease and associated disorders · 85 citationsread the source →

Research Summit III Proceedings on Dosing in Children With an Injured Brain or Cerebral Palsy: Executive Summary

Children with brain injuries or cerebral palsy (CP) comprise a large percentage of pediatric clients served by physical therapists. There is no consensus on what the basic parameters should be for different treatment protocols. A very important parameter of intervention that is pivotal for treatment efficacy is dosing. Dosing decisions are complex. To date, the minimum doses for changing structure and function, activity, and participation in children with various disabilities are unknown. This article describes the process and outcomes of a research summit with the goals of: (1) fostering a critical debate that would result in recommendations for the development of large-scale, second-generation research proposals to address thresholds for effective dosing of interventions for children with brain injuries or CP and (2) enhancing the research capacity of pediatric physical therapists through collaborative research networks. The summit brought together an interdisciplinary cadre of researchers (physical therapists, basic and clinical scientists), representatives from funding agencies, and consumers to an intensive 2.5-day think tank. The summit targeted questions of treatment dosage related to 3 areas: practice and neuroplasticity, structure-behavior connections, and clinical trial design. The consensus was that the intervention must demonstrate some evidence of effectiveness before optimal dosing can be investigated. Constraint-induced movement therapy (CIMT) is used as an example of an intervention that has demonstrated effectiveness and that requires dosing-related research. Summit results, including factors that merit special consideration and recommendations for future dose-related studies, are highlighted. Physical therapy is an important service for children with physical disabilities, particularly those with an injured brain resulting in neuromotor impairments and functional limitations.1 These children typically have multiple health complications that often result in complex functional limitations and require extensive health care, education, and vocational training. The costs of interventions result in substantial financial and social challenges for families and society.2 Although physical therapists frequently provide continuous interventions for children with physical disabilities, including CP,3 there remains limited empirical support for these services.4 Dosing represents a critical and pressing aspect of intervention that is central for treatment efficacy. In this article, dose is defined as the frequency, intensity, time, and type of an intervention.5Frequency refers to how often, such as the number of sessions for a given intervention per day, week, or month. Intensity refers to how hard the child works within the intervention session and is recorded as the number of repetitions per minute, day, or week or amount of work (eg, 75% of maximal heart rate). Time refers to the duration of the intervention. Type refers to the kind of intervention and can be focused at any of the dimensions of the International Classification of Functioning, Disability and Health (ICF): body functions and structures, activity, or participation.6 Within types, variation exists. For example, task practice can vary in the type of behavioral shaping (ie, structured versus unstructured training) and amount of feedback or reward. Type of intervention is central to the discussion because determining the “salient” or “active” ingredient of an intervention strategy is intimately related to the question of dosing. What is “it” that should be dosed? Intervention strategies also involve interactions with biomechanical, neuromuscular, and psychological elements of a child's behavior, necessitating insight into the mechanism leading to a change in behavior. Consequently, the nature of optimal dosage can be expected to vary with different types of interventions. Intervention-related dosing is a source of disagreement among service providers, policy makers, insurers, and researchers, whose recent findings show the potential for high dosing intervention to be the catalyst for positive intervention outcomes.7 The cost related to high dosing is one impediment to implementation. Another is uncertainty about the minimal dose that is effective and sufficient. Some of the most promising targeted interventions that seek to promote plastic changes in the brain and muscle, such as training on a treadmill,8 CIMT,9–12 and strength training,13,14 have used varying doses. The findings from these studies have highlighted a complex dosing knowledge gap, namely, a disconnect between structural and behavioral changes, where changes that are seen at one dimension of the ICF are not always incorporated into others. The disconnect between structural and behavioral changes15 provides a compelling argument for revisiting hypotheses regarding mechanisms for adaptive motor learning and for a critical examination of dosing at the cellular, structural, activity, and participation levels. Collectively, these findings and the question of dosing suggest that scientific exploration of the effect of dosing in pediatric physical therapy and its interaction with other aspects of intervention will be a challenging enterprise. The findings suggest that for the field of pediatric physical therapy or rehabilitation to move forward, the dosing question will require an interdisciplinary coordinated effort, using sound conceptual frameworks and a systems perspective. A research summit offers a plausible launching pad for promoting an interdisciplinary coordinated effort and addressing some of these complex questions related to dosing. In this article, we define a research summit as a think-tank mechanism whereby different parties can contribute to the development of well-crafted research programs or action plans designed to move science on a specific topic to the next level. For the past 9 years, the Section on Pediatrics of the American Physical Therapy Association (APTA) has used interdisciplinary research summits developed by the first author and colleagues to foster development of large-scale research proposals on a topic of great importance to pediatric practice and simultaneously increase the research capacity of pediatric physical therapists. The results have shown that, with creative and meaningful collaborations, short-term intensive meetings can help increase the numbers of pediatric therapists with postprofessional doctoral training who are successful in securing funding to conduct research on a targeted topic that advances practice. The first research summit (RS I), in 2004, addressed physical fitness in children with CP and secondary complications.16 To date, this summit has resulted in 71 publications, 36 presentations, and 29 funded grants, 6 of which were from the National Institutes of Health (NIH), totaling more than $2 million. The second summit (RS II), in 2007, focused on early intervention for children with or at risk for disabilities. It has resulted in 34 publications, 34 submitted grants, and 14 funded grants, 2 from NIH and 2 from the National Institute on Disability and Rehabilitation Research (NIDRR), totaling more than $900,000. Many of the grant proposals have involved collaboration between several physical therapists and non–physical therapist summit participants. The current research summit (RS III) was modeled after these 2 highly successful summits to direct research attention to the critical issue of dosing of interventions for children with an injured brain. The goals of RS III were: (1) to foster a critical debate that would result in recommendations for the development of large-scale, second-generation research proposals to address thresholds for effective dosing for children with an injured brain or CP and (2) to enhance the research capacity of pediatric physical therapists by facilitating collaborations, information exchange (cross-fertilization), and networking among physical therapists, other researchers (basic, neuroscience, movement, and clinical scientists), consumers, and funding agencies in the area of dosing of interventions for children with an injured brain or CP. The summit was held in Alexandria, Virginia, in October 2011. This article summarizes the highlights of the summit deliberations, factors that merited special consideration regarding dosing interventions, and recommendations for dosing studies that will help advance this area. The emphasis was on 3 body structures known to be affected by injury to the brain, rehabilitation, and dosing: muscle, bone, and brain.17–19 We used the ICF6 as an organizing framework. In addition to discussing issues related to direct intervention strategies, we also emphasized patient and family education and addressed the importance of activity, participation, and family dynamics. We illustrate the need for sequential and systematic studies of dosing and the salient features of intervention upon which dosing parameters should be based by summarizing the findings from an intervention with known efficacy (CIMT) that still requires dosing-related research. A total of 48 individuals (see Appendix) participated in the summit. The planning committee, with the help of other researchers and representatives of funding agencies, identified 12 scientists with relevant expertise in neuroscience, movement science, pediatrics, muscle and exercise physiology, imaging, bone health, neurology, occupational therapy, and statistics. Also invited were representatives from APTA, funding agencies and foundations, and 4 consumers. The committee identified 2 physical therapy researchers with established research agendas and a history of federal funding (Dr Stuart Binder-Macleod and Dr Diane Damiano) to serve as facilitators. Details of participants are listed in Table 1. Characteristics of Research Summit Participants Characteristics of Research Summit Participants Participation by additional pediatric physical therapists was through an application process. An independent review committee selected 17 physical therapist participants who met one or more criteria: history of funded research in the area of interventions or measurement for children with neurological disorders, currently conducting research (funded or unfunded) in this area, or postprofessional physical therapist students who are mentored by researchers conducting clinical trials or intervention research. All participants submitted a 3-page biographical sketch and a 2- to 4-page position or perspective paper that focused on the subject of dosing and expectations from the summit and highlighted their own research. The biographical sketches and position or perspective papers were disseminated to all participants before the summit to maximize information sharing and help participants become familiar with one another's research and expertise, thereby facilitating networking and communication during the summit. The planning committee applied for and received funding from APTA's Section on Pediatrics, the National Institute of Child Health and Human Development, and the National Institute of Neurologic Disorders and Stroke to support the cost of the summit. The RS III was a 3-day conference designed to systematically address the current state of clinical research in the area of intervention dosing and to create research networks and goals. The first day focused on information exchange and identification of knowledge gaps. The second day built on the information presented on the first day by formulating scientific questions and considering research designs to explore dosing. The day was to the development of action and research The the of the summit. and of Research Summit The and and of 2 by representatives from funding agencies, and or by participants. The first address was by Dr an established in clinical The goals of this address were to the and to of the in the area of intervention dosing. A of 2 family and 2 individuals with CP the second All were from the area and in of and The goals for the were to the of on the of clinical practice and the of or for the were to provide a catalyst for and and of the of dosing and its and potential research by all participants were to define the of by the to the and of research in which participants are exchange information on current and past research and potential for and strategies for The goals of these were: (1) to promote the of (2) to research to research questions that would to research and to promote discussion of research action and researchers were with based on of or There were a total of 3 discussion of at (1) practice and or muscle and in children with injured or (2) structural and behavioral changes and and clinical These 3 were by the planning committee to be the for the of intervention dosing and emphasized muscle, bone, and brain. Participants were for the first 2 sessions and to for the session based on research and potential of the topic of were presented to the large for an discussion and consensus for future collaborative research The the to the and at the and of the summit the to and of the planning committee served as to the of the goals of the to the summit goals and to the and for In the that we and from and specific aspects that merited critical consideration on the topic of and recommendations for research by the summit participants. from the of bone and brain are used to of research that were in the summit. The consensus from the first discussion that the and by research participants and representatives from funding agencies was that dosing is a Participants that the minimal and optimal dosage of interventions would on the neuromuscular, and of the children the nature of the intervention the type of functional goals to be and and A by Dr in address was to the salient of the intervention that to changes in motor and to be repetitions of movement per of intervention per day, per week, total number of and amount of intervention. the of of clinical questions of of of and total of intervention are related as are their The was that of these would require its own of studies or that the interaction of these should be in effectiveness research. Another by the information presented by the of consumers, was to the interaction of dose with other interventions used in pediatric rehabilitation, often within or The that because dosing need to be for a systematic exploration of dosing would be a research from the first the need to the effectiveness or mechanism of for specific types of interventions within and and must seek to address the question of some changes are and some are studies also must address and factors to with plastic changes in the bone, and of the of the bone of children with CP or injured a for considering specific and Dosing research questions bone in children with CP should exercise that the in the are most to with and are more is between The of be based on a child's of and change as a child to the exercise the repetitions with more between exercise sessions to maximize the of dosing will be important has a at which factors that have the potential to enhance and the potential of a such as and or also need to be In the requires a duration a minimum of 3 to a to exercise with other systems such as and muscle dose-related questions were to be different on the of the of questions are presented in Table of Research What is the minimal and optimal dose of for important change in is the change and What is the optimal dose of physical to increase muscle the and increase participation in with and What are the minimal and optimal doses of training to and functional in children with CP What is the minimal and optimal dose of for important change in is the change and What is the optimal dose of physical to increase muscle the and increase participation in with and What are the minimal and optimal doses of training to and functional in children with CP movement therapy, Classification of Research What is the minimal and optimal dose of for important change in is the change and What is the optimal dose of physical to increase muscle the and increase participation in with and What are the minimal and optimal doses of training to and functional in children with CP What is the minimal and optimal dose of for important change in is the change and What is the optimal dose of physical to increase muscle the and increase participation in with and What are the minimal and optimal doses of training to and functional in children with CP movement therapy, Classification from the discussion based on from on structure-behavior (1) that current intervention studies have outcomes that not always to (2) that changes to be and that the results through intervention are specific (ie, what of these that the high doses of for children with CP has not to in functional of the affected in muscle structure have with limited changes in studies have demonstrated in capacity in children who received training and in those who received 2 of research questions identified by the that, would help to to dosing questions and structure-behavior to the need to structure-behavior was the consideration that outcomes in the are the also must be to the intervention in the not the not outcomes must of and change has The was that studies of intervention dosing must the minimum and optimal doses that can all of the ICF that are and to The also highlighted the importance of using and of patient and in addition to of intervention and The of that ICF and the of the of with and cost were from the clinical with knowledge of the mechanisms brain or in children with dose-related research also must involve of of body structure and that changes in and The of of at the of the ICF was These be with from recent advances in such as and The of is at the participation level. The outcomes such as adaptive which that to the child's level. have developed and to physical the of the which was developed by NIH to provide a of highly measurement of health for and social The of and with children with CP has the of several recent The discussion session on clinical trials and other research designs identified 3 of (1) minimal dose and optimal dose for important (2) optimal dose to and functional in children with CP Classification and which the optimal dose of physical to the to increase muscle and bone and bone and the between and outcomes in studies or effectiveness research (ie, what works for and and the potential and of an A of the extensive on dose-related and as to these 3 are The also as recommendations for future dose-related research trials and studies, including effectiveness were as strategies for a critical of to address the dosing questions and challenges should and interventions that have the potential to meaningful change for the child and family and that are and and effective dose must involve a sequential of related hypotheses and of effectiveness in a meaningful should by studies to the minimal dose for or the The sequential should require identification of the salient of the intervention that to changes in of the participants and questions of frequency, intensity, and of a type of intervention which are related as as including such as child For the intervention to be at the of an intervention must be which would require at one after more would have would need to strategies such as a which is a to of to to is the of intervention This refers to changes at different during an intervention to information on the at what different outcomes were and intervention that to This that dosing-related studies will require designs than Although all that would be to optimal was that other factors the dose would the would need to be as and factors will or the must be and in factors must of and family The that the should be on all to interventions that have the potential to meaningful change for the child and family and that are and in to interventions is in to that are and the of the of will be by the among these factors and the factors The question for researchers should What aspects of the and with intervention doses to The about of therapy, as children and on the importance of the of therapy to the child's current such as or dose-related studies will require of designs and or conceptual The for an of in research and training and that such should be early in the process of grant or The the need to an minimal or of outcomes for studies with such as those with the of or such as the NIH and consideration and exploration as outcomes for dosing are one to the effectiveness of interventions, the of outcomes was as of great importance in addressing dosing the consensus was that the intervention must demonstrate some evidence of effectiveness before optimal dosing should be investigated. An example of an intervention that has demonstrated effectiveness and that requires dosing-related research is with This intervention also was selected as a future area by one during the to address the question of a minimal dose and optimal dose for important What is a of the in Table that dosing be from the various other parameters of intervention that with of the Therapy (CIMT) and to A of more than children or of or intensive therapy show that of training resulted in or of at than of training. Classification of Functioning, Disability and of the Therapy (CIMT) and to A of more than children or of or intensive therapy show that of training resulted in or of at than of training. Classification of Functioning, Disability and children with CP and to were given 6 of intervention per day functional task practice with shaping (ie, training with positive for in children with CP and 2 to 6 years, was that 3 per day, for results that were research that the duration of training from to the number of of training per day at 3 not the of the affected by was per day in of the Another early research developed in demonstrated motor learning after extensive In this and with the more affected were It should be that there studies of pediatric all of these studies the intervention with a or and at dosing that be a of than the type of intervention the development of intensive therapy trials of and have shown that demonstrated in and of the as a in of the during a suggest the importance of of practice show that of training resulted in and of at than of training. This example highlights the importance of research to the specific and their to The of this summit was to foster a critical debate that would result in recommendations for the development of large-scale research proposals to address dosing for children with injured or CP. presented in the that the summit was successful in fostering a critical debate on this topic and recommendations for research on this The next for intervention dosing are in Table 4 and what RS III physical therapists, and different can to that intervention dosing be a research and to foster on a for Research on movement therapy, for Research and Physical Therapy International Research for Research on movement therapy, for Research and Physical Therapy International Research The second of enhancing the research capacity of pediatric physical therapists by facilitating and networking was as by how the for the Some of the on to and 2 interdisciplinary planning that were funded by the Section on Pediatrics in physical therapists served as in we the of this summit to increase with Summit participants will be 2 about submitted grants, funded and that resulted from this summit. This research summit was the first and in a systematic and of dosing questions and an interdisciplinary second-generation dose-related research. The consensus is that an intervention must demonstrate effectiveness before dose-related studies can be In this article, we the process and of the highlighted several factors that merit special consideration for dosing studies, and recommendations for clinical trials and other strategies to advance research on this The recommendations are to second-generation intervention research questions and targeted interdisciplinary foster of rehabilitation at all of the and the of children with an injured brain or CP. Section on Pediatrics Research Summit The Research Summit III and for Children an or was by the American Physical Therapy Association (APTA) Section on Pediatrics, the National Institutes of National Institute of Child Health and Human and the National Institute of Disorders and Stroke October Alexandria, at the of Research Summit III are Section on Pediatrics Research Summit The Research Summit III and for Children an or was by the American Physical Therapy Association (APTA) Section on Pediatrics, the National Institutes of National Institute of Child Health and Human and the National Institute of Disorders and Stroke October Alexandria, at the of Research Summit III are

Physical Therapy · 69 citationsread the source →

Social and demographic predictors of preschoolers' bedtime routines.

Objective: To examine the associations of child and family sociodemographic characteristics with preschooler bedtime routines. Method: We use parent-report data of 3217 3-year-old children (48% black, 26% Hispanic, and 22% white) from the Fragile Families and Child Wellbeing Study to examine whether child and family characteristics are associated with the presence, time, and consistency of bedtime routines. Results: More than 80% of sample children have a bedtime yet only two thirds follow it. After extensive controls for maternal education, family structure, and other household characteristics, black and Hispanic children have later bedtimes than white children and reduced odds of using regular bedtimes (by 22% and 29%, respectively) and using bedtime routines (by 47% and 33%, respectively). Low maternal education, increased household size, and poverty are associated with decreased use of parent-child interactive and hygiene-related bedtime routines. Conclusion: Children from disadvantaged households are less likely to have consistent bedtime routines than their more advantaged counterparts. This may contribute to later disparities in sleep quality, duration and timing, factors known to be associated with adverse behavioral, cognitive, and health outcomes.

Journal of developmental and behavioral pediatrics : JDBP · 152 citationsread the source →

Problematic Internet use: an overview

The “global village”, a metaphor used to describe how the Internet has shortened distances and facilitated the flow of information, has grown to over one billion users 1. Statistics from across the world highlight its reach and penetrance: 90% of South Korean households connect to high-speed, inexpensive broadband 2; Londoners spend an average of 45 days a year online, more than they spend watching TV 3; and the rate of increase in the number of Internet users in Africa and the Middle East exceeded 1,300% between 2000 and 2009 4. For the majority of Internet users, the World Wide Web represents a tremendous wellspring of opportunity that enhances well-being. For others, however, it can lead to a state that appears to meet the DSM definition of a mental disorder, described as a “clinically significant behavioral or psychological syndrome…that is associated with present distress… or with a significantly increased risk of suffering death, pain, disability, or an important loss of freedom” 5. Scientific understanding of that state has lagged behind media attention 6, in part because of inconsistency in defining the problem 7, disagreement about its very existence 8, and the variable research methodology used in studying it. Still, a body of data by scientists from the East and West (with the East increasingly leading the way) tells a cautionary tale about the Internet's potential to bring about psychological harm. In 1996, the psychologist K. Young became the first to publish a detailed case report of problematic Internet use 9. Her “patient zero” was a non-technologically oriented 43-year-old homemaker with a “content home life and no prior addiction or psychiatric history”, who, within three months of discovering chat rooms, was spending up to 60 hours per week online. She reported feeling excited in front of the computer, and depressed, anxious, and irritable when she would log off. She described having an addiction to the medium “like one would to alcohol”. Within one year of purchasing her home computer, she was ignoring household chores, had quit social activities she used to enjoy, and had become estranged from her two teenage daughters and her husband of 17 years. Based on this and other patients she interviewed, Young proposed the first set of diagnostic criteria for what she termed “Internet addiction”. She modeled them on the DSM-IV definition for substance dependence because of similarities she observed with the states of tolerance (needing more of the substance to achieve the same effect) and withdrawal (psychological and physical discomfort upon reducing or stopping the substance) 9. Others conceptualized problematic Internet use as a behavioral addiction not involving an intoxicant 10, and Young subsequently updated her definition, adapting the DSM-IV criteria for pathological gambling, an impulse control disorder often described as a behavioral addiction, into her Diagnostic Questionnaire 11 (Table 1). The questionnaire, which required at least five of the eight criteria be met for the Internet addiction diagnosis, has not received adequate psychometric testing. Shapira et al 12 proposed five years later a more inclusive diagnostic schema in the general style of the impulse control disorders. They argued that definitions based solely on substance dependence or pathological gambling were too narrow to capture the population of problematic Internet users and could lead to premature conclusions about the new disorder and the patients. They eschewed the “Internet addiction” label for lack of scientific proof for true addiction and favored the less controversial “problematic Internet use”, defining it as: a) maladaptive preoccupation with Internet use, experienced as irresistible use for periods of time longer than intended; b) significant distress or impairment resulting from the behavior; and c) the absence of other Axis I pathology that might explain the behavior, such as mania or hypomania. To date, only two studies have attempted to develop diagnostic criteria empirically by testing them against the diagnosis made on the basis of a systematic psychiatric interview. Ko et al 13 tested a set of criteria in 468 Taiwanese high school students. Starting with 13 candidate criteria, they eliminated those with low diagnostic accuracy, and determined that a cutoff of six out of the nine remaining criteria had the best diagnostic accuracy while maintaining high specificity (97.1%) and acceptable sensitivity (87.5%). The criterion for functional impairment was listed separately as criterion B and was required for the diagnosis (Table 2). In a second study, Ko et al 14 confirmed the diagnostic accuracy of their criteria in an older cohort of 216 Taiwanese college students. However, the relatively small size of both studies and the non-representative nature of the groups studied limit the applicability of the proposed criteria to the general population. Several assessment scales have been proposed to screen for, and help diagnose, problematic Internet use. As a group, these instruments show no consensus on the underlying dimensions that constitute the condition 6,15. In addition to Young's Diagnostic Questionnaire, two are in relatively common use in research and/or clinical settings: Young's Internet Addiction Test 16 and the Chen Internet Addiction Scale 17. Young's Internet Addiction Test 16 consists of 20 “how-often” questions, each rated on a scale of 1 to 5 (1=rarely; 2=occasionally; 3=frequently; 4=often; 5=always.) A score of 80 or above is consistent with problematic use (Table 3). The psychometric properties of the instrument were studied in 86 subjects 18. Six factors were extracted from the questionnaire: salience, excessive use, neglect of work, anticipation, lack of control, and neglect of social life. These factors showed good concurrent validity and internal consistency. Salience explained most of the variance and was also found to be the most reliable as indicated by its Cronbach's alpha. However, the selection bias introduced by online recruitment and the small size of the study limit its value. The Chen Internet Addiction Scale 17 is a self-report instrument composed of 26 items rated on a 4-point Likert scale (adapted in Table 4). It assesses five domains of Internet-related problems: compulsive use, withdrawal, tolerance, interpersonal and health consequences, and time management difficulties. Scores range from 26 to 104. In a study of 454 Taiwanese adolescents who completed the scale and received a structured diagnostic interview, a cutoff of 64 was shown to have high diagnostic accuracy and specificity (88% and 92.6%, respectively) 19. The internal reliability of the scale and subscales in the original study ranged from 0.79 to 0.93 17. Due to the lack of consensus on diagnostic criteria and the dearth of large epidemiological studies, the prevalence of problematic Internet use in the general population has not been established. Overall, prevalence surveys conducted in various countries fall into two main categories, online vs. offline studies, with the former typically yielding higher rates, most likely because of inherent selection bias 20. Only two epidemiological studies exploring the prevalence of problematic Internet use in the general population have been published. One was conducted in the US, the other in Norway 20,21. The US study used random-digit telephone dialing (cellular phone numbers were not included) to interview 2,513 adults taken from all 50 states in a manner proportional to the population in each state 20. More than half of the people reached agreed to be interviewed. Participants’ average age was 48, and 51% fell in the middle class socioeconomic stratum. 68.9% were regular Internet users. The authors’ diagnostic definition, based on published criteria and on similarities with impulse control disorders, substance dependence and obsessive-compulsive disorder, required: a) Internet use that interferes in personal relationships; b) preoccupation with the Internet when offline; c) unsuccessful attempts at quitting or cutting down; and d) staying online longer than intended. This definition yielded a point prevalence of 0.7%. Less stringent definitions yielded higher prevalence rates, and individual features consistent with problematic Internet use were endorsed by as many as 13.7% (respondents who found it hard to stay offline for days in a row). In the second study, Bakken et al 21 mailed Young's Diagnostic Questionnaire to 10,000 inhabitants of Norway, randomly selected from a database of the entire population. 3,399 completed questionnaires were returned (a somewhat lower response rate than the US study). Recipients of the mailed questionnaire also had the option of completing it online. Among respondents, 87% were Internet users. The prevalence of “addicted Internet use” (≥5 questions answered “yes”) was calculated to be 1%, whereas the prevalence of “at risk” Internet use (3–4 questions answered “yes”) was 5.2%. Multivariate analysis showed young age, male gender, higher educational achievement, and financial stress to be positively associated with “problematic Internet use” (defined by the authors to include both “Internet addicts” and “at risk” respondents). Prevalence rates among adolescents have been researched more extensively, perhaps because the so-called “digital natives” grew up incorporating the Internet in many aspects of life and as a result are perceived to be at higher risk. However, even when online-based surveys are excluded, the results can vary widely and are difficult to compare, due to differences in Internet access, recruitment methodology, the exact age bracket studied, and the definitions utilized. Considering only relatively large and offline studies, research from China 22, South Korea 23,24, Greece 25, Norway 26, and Iran 27 has yielded prevalence estimates ranging between 2% and 11%. Problematic Internet use has not been incorporated into large-scale epidemiological studies aimed at estimating the relative prevalence of mental disorders. Still, a review of published studies reveals that the presence of other psychiatric conditions in patients with problematic Internet use is the rule rather than the exception 6. The studies, however, were not designed or statistically powered to detect the nature of the association (cause, effect, or independent). In Bakken's general-population study 21, based on subjects’ self-report, 41.4% of Internet “addicts” reported feelings of depression in the 12-month period prior to the study, compared to 15.8% of non-problematic users. Sleep disturbances, anxious feelings, and alcohol and substance abuse were also more common (38.6% vs. 26.4%, 36.4% vs. 5%, and 13.6% vs. 1.1%, respectively). However, the questions used to assess co-occurring psychological impairment were not based on established criteria for mood, sleep, anxiety, or substance use disorders. Two US case series involved face-to-face interviews of adult patients with problematic Internet use. Black et al 28 assessed 21 subjects with the Diagnostic Interview Schedule and found the lifetime prevalence of mood disorders and major depression to be 33% and 15%, respectively. Further, 38% had a lifetime substance use disorder and 19% had a lifetime diagnosis of anxiety disorder. In a case series that included 20 patients, Shapira et al 29 found a very high (70%) lifetime prevalence for bipolar affective disorder, type I or II, compared with 15% for major depression. Fifty-five percent had a lifetime prevalence of substance abuse, and 45% met criteria for social anxiety disorder. Fifty percent of subjects had a lifetime diagnosis of an impulse control disorder. The authors highlight their observation that patients’ Internet-related symptoms were more impulsive and egosyntonic than compulsive and egodystonic, concluding that problematic Internet use resembles the DSM-IV definition of an impulse control disorder more closely than that of obsessive-compulsive disorder. Our clinical experience supports this conclusion. As a group, surveys conducted among high school and college students show similarly high comorbidity rates with mood and anxiety disorders, but a link between attention-deficit/hyperactivity disorder (ADHD) and problematic Internet use seems more obvious than among adults. One study in 752 South Korean elementary students found that 33% of those with ADHD also met criteria for problematic Internet use 30. Another study in 216 Taiwanese college students showed that 32% subjects with problematic Internet use also had ADHD compared to only 8% of regular Internet users 31. Whether Web-based activities appeal to the short attention span of ADHD sufferers or whether excessive Internet use may cause inattention remains to be elucidated. The clinical evaluation of the patient with problematic Internet use should include a careful assessment of the comorbid conditions frequently present. Those should then be treated according to established treatment guidelines. To the extent that the Internet-related problem may stem from another diagnosis (e.g., a patient with severe social anxiety who starts leading a “virtual” life at the expense of offline interactions), it might improve as the primary condition is addressed. Pharmacotherapeutic and psychotherapeutic interventions specific to problematic Internet use have not yet received adequate testing in large, rigorous studies. Pharmacotherapy often begins with selective serotonin reuptake inhibitors (SSRIs). However, while effective in treating obsessive-compulsive disorder, SSRIs have shown mixed results in impulse control disorders 32,33,34,35–36. In light of the greater similarity between problematic Internet use and impulse control disorders compared to obsessive-compulsive disorder 29, it is unclear whether SSRIs will ultimately prove beneficial, and no double-blind placebo-controlled studies have been published so far. One discontinuation study tested escitalopram, 20 mg/day, in 19 subjects with problematic Internet use 37. During the 10-week open-label phase, subjects showed significant decreases in weekly hours spent online (from a mean of 36.8 hours to 16.5 hours) and improvement in global functioning. At the end of the 10 weeks, subjects were blindly randomized to either continued escitalopram treatment or to placebo. Beyond that, they were followed for 9 weeks. No significant difference was seen between the two groups at the end of the second phase, as gains achieved at week 10 were maintained in both treatment groups. The authors speculate that nine weeks may have not been sufficient for the effect to be lost in the placebo group or for additional gains to be made in the escitalopram group, but do not rule out the possibility that the improvement seen in the open-label phase may have been a placebo response. One case study reported successful treatment with naltrexone 38, a drug that has shown benefit in other impulse control disorders 39,40. The patient was a 31 year old male with compulsive cybersexual behavior who had failed antidepressants, group and individual psychotherapy, Sexual Addicts Anonymous, and pastoral counseling. Naltrexone (150 mg/day), gradually added to a stable dose of sertraline which on its own had been ineffective in treating his problematic Internet use, helped induce a three-year remission. The authors hypothesize that, by blocking the capacity of endogenous opioids to trigger dopamine release in response to reward, naltrexone may block the reinforcing nature of compulsive Internet sexual activity. Another case study reported the successful use of an atypical antipsychotic, quetiapine, 200 mg/day, gradually added to citalopram, in a 23 year old subject with problematic Internet use 41. The improvement was maintained at four-month follow-up. More recently, a study tested methylphenidate in 62 children with ADHD who were Internet video game players 42. Participants’ average age was around 9. After 8 weeks of treatment (average dose 30.5 mg/day), Internet usage decreased significantly and correlated with reduction in ADHD symptoms. The authors cautiously suggest that methylphenidate might be beneficial as a treatment for problematic Internet use, especially when co-occurring with ADHD. Of the psychotherapy approaches used, cognitive behavioral therapy (CBT) has received the most empiric investigation. The largest study enrolled 114 adult subjects and employed CBT interventions including: keeping a daily log of Internet activity, teaching time management skills, and confronting cognitive distortions and rationalizations frequently used by patients to justify continued Internet usage, such as “just a few more minutes won't hurt” 43. Most subjects were able to control their symptoms by the eighth session, and improvement was sustained over a 6-month follow-up. For children and adolescents, family-based interventions that improve communication and teach family monitoring of Internet use can be helpful 44. However, the intensive (and typically very expensive) residential treatment options that have received much media attention have undergone little empiric investigation to warrant a strong recommendation 2,45. The same applies to online treatment websites that encourage the person with problematic Internet use to “click here if you are addicted to the Internet”. For a medium that has so radically changed the way we conduct our lives, the Internet's effects on our psychological health remain understudied. Simply stating that similar fears were raised when the radio, movies and early video games were introduced is not sufficient: the immersive and interactive qualities of the virtual world, and its sheer penetrance, make it potentially more serious. Also deserving of exploration are the more subtle psychological changes that occur in the virtual world, such as online disinhibition and increased risk-taking 46. Those changes are not necessarily evidence of “Internet addiction”, and may not be pathological, but, as important features of the new virtual psychology, should also be studied. As our field continues to debate whether their condition belongs in the next edition of the DSM 47, patients continue to present with symptoms born out of the digital age, and their symptoms are changing as the technology evolves from browsers, to “crackberries”, to “smart phones” that combine texting, talking, video games, and browsing in one device that to many is like a new appendage. Even the “problematic Internet use” designation now seems outdated, which is why some have wisely opted for “pathological use of electronic media”, instead 47. Technology, like media outlets, remains far ahead of scientific investigation. Given the dramatic changes that our society is undergoing as a result of the Internet revolution, it behooves us to try to bridge the gap.

World Psychiatry · 340 citationsread the source →

Death Anxiety in the Elderly: The Role of Spiritual Health and Perceived Social Support

Aging as one of the most important periods of life is associated with many challenges including death anxiety. Therefore, the aim of the current study was to investigate the role of spiritual health and perceived social support in predicting death anxiety in the elderly. The present study was a descriptive-correlational one. The study population consisted of the elderly living in Shahrekord in 2020, among whom 385 were selected using convenience sampling method and were assessed by the scales of Templer Death Anxiety, Zemen Perceived Social Support and Paloutzian & Ellison spiritual health. Data were analyzed using correlation coefficient and linear regression analysis in SPSS software version 22. The results indicated that there is a significant relationship between spiritual health (r=-0.51), perceived social support by family (r=-0.37), friends (r=-0.30) and significant other (r=-0.16) with death anxiety in the elderly. The results of linear regression analysis releaved that spiritual health (P=0.001, β=-0.46) and perceived social support by the family (P=0.001, β=-0.29) can predict negatively the death anxiety in the elderly and explain 26.7% of the variance of death anxiety in the elderly. Consequently, counselors and psychologists in the field of aging are suggested to reduce death anxiety in the elderly, using strategies to promote spiritual health and social support. ReferencesAbdel-Khalek, A. M. (2001). Death, anxiety, and depression in Kuwaiti undergraduates. OMEGA-Journal of Death and Dying, 42(4), 309-320.Abdel-Khalek, A. M. (2005). Death anxiety in clinical and non-clinical groups. Death Studies, 29(3), 251-259.Alipour, A., Aliakbari Dehkord, D. M., Amini, F., & Hashemi Jashni, J. A. (2016). Relationship between perceived social support and adherence of treatment in Diabetes Mellitus type 2: mediating role of resiliency and rope. Journal of Research in Psychological Health, 10(2), 53-67. 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B., Rocha, G. P., Fernandez, L. L., de Padua, A. C., & Reppold, C. T. (2018). Association of lower spiritual well-being, social support, self-esteem, subjective well-being, optimism and hope scores with mild cognitive impairment and mild dementia. Frontiers in psychology, 9, 1-10.Ebrahimi, B., Hosseini, M., & Rashedi, V. (2018). The Relationship between social support and death anxiety among the elderly. Elderly Health Journal, 4(2), 37-42.Emamirad, A., Amiri, H. (2018). The Relationship between spiritual health and meaning of life with death anxiety in elders. Aging Psychology, 4(3), 251-261. [Persian]Esmaeilishad, B. (2020). The Effectiveness of self-care training on quality of life, self-care behaviors and blood sugar in elderly lacking self-Care behaviors. Aging Psychology, 6(1), 1-11. [Persian].Fortner, V., Robert A. Neimeyer, B. (1999). Death anxiety in older adults: A quantitative review. Death studies, 23(5), 387-411.Ghasempour, A., Sooreh, J., & Seid Tazeh Kand., M.T (2017). 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Factors influencing death anxiety in community-dwelling elderly: based on the ecology theory. The Korean Journal of Hospice and Palliative Care, 22(1), 30-38.Krause, N., Pargament, K. I., & Ironson, G. (2018). In the shadow of death: Religious hope as a moderator of the effects of age on death anxiety. The Journals of Gerontology: Series B, 73(4), 696-703.Kübler-Ross, E. (2002). On death and dying; Questions and answers on death and dying; on life after death. Quality Paper Book Club. Kurtulan, M. H., & Karaırmak, Ö. (2016). Examination of the relationship among death anxiety, spirituality, religious orientation and existential anxiety. Spiritual Psychology and Counseling, 1(2), 206-217.Lehto, R. H., & Stein, K. F. (2009). Death anxiety: an analysis of an evolving concept. Research and theory for nursing practice, 23(1), 23–41.López‐Cerdá, E., Carmona‐Torres, J. M., & Rodríguez‐Borrego, M. A. (2019). Social support for elderly people over 65 years in Spain. International nursing review, 66(1), 104-111.Mahbobi, M., Etemadi, M., Khorasani, E., & Ghiasi, M. (2012). The Relationship between spiritual health and social anxiety in chemical veterans. Journal of Military Medicine, 14(3), 186-91Mehri Nejad, S. A., Ramezan Saatchi, L., & Paydar, S. (2017). Death anxiety and its relationship with social support and adherence to religion in the elderly. Salmand: Iranian Journal of Ageing, 11(4), 494-503. [Persian].Menzies, R. E., & Dar-Nimrod, I. (2017). Death anxiety and its relationship with obsessive-compulsive disorder. Journal of Abnormal Psychology, 126(4), 367.Michaelson, V., Brooks, F., Jirásek, I., Inchley, J., Whitehead, R., King, N., Walsh, S., Davison, C., Mazur, J., & Pickett, W. (2016). Developmental patterns of adolescent spiritual health in six countries. SSM-population health, 2, 294-303.Moser, S., Luxenberger, W., & Freidl, W. (2017). The influence of social support and coping on quality of life among elderly with age-related hearing loss. American Journal of Audiology, 26(2), 170-179.Poordad, S., Momeni, K., & karami, J. (2019). Death anxiety and its relationship with social support and gratitude in older adults. Salmand: Iranian Journal of Ageing, 14(1), 26-39. [Persian].Rajabi, G.R., & Bahrani, M. (2001). Factor analysis of death anxiety scale questions. Journal of Psychology, 5 (4), 331-341. [Persian].Razavi, V. (2015). Relationship between social support and hope and death anxiety among the old people of Tehran Omid Cultural Center. International Journal of Life Sciences, 9(2), 65-70.Rocha, A. C. A. L. D., & Ciosak, S. I. (2014). Chronic disease in the elderly: spirituality and coping. Revista da Escola de Enfermagem da USP, 48(2), 87-93.Rostami, M., nosrati, K., Mahdinejad Gorji, G., kabiri, M. (2020). Death anxiety in the elderly: the role of psychological hardiness and practical commitment to prayer. Aging Psychology, 5(4), 309-320. [Persian]Russac, R. J., Gatliff, C., Reece, M., & Spottswood, D. (2007). Death anxiety across the adult years: An examination of age and gender effects. Death studies, 31(6), 549-561.Saber, F. M., & Nusratabadi, M. (2014). Social support and quality of life related to health in the elderly covered by the welfare of Kerman city. Journal of Health and Development, 3 (3), 189-199. [Persian].Saini, P., Patidar, A. B., Kaur, R., Kaur, M., & Kaur, J. (2016). Death anxiety and its associated factors among elderly population of Ludhiana city, Punjab. Indian Journal of, 30(1), 101-10.Sarason, B. R., Sarason, I. G., & Pierce, G. R. (1990). Social support: An interactional view. John Wiley & Sons. Seo, J. H., & Noh, Y. G. (2019). Influences of social support and health promotion behavior on aging anxiety among middle-aged women. Journal of Digital Convergence, 17(11), 339-347.Seyedfatemi N., Rezaie M., Givari A., & Hosseini F. (2006). Prayer and spiritual well-being in cancer patients. Health Monitor Journal of the Iranian Institute for Health Sciences Research, 5(4), 0-0. [Persian].Sharma, P., Asthana, H. S., Gambhir, I. S., & Ranjan, J. K. (2019). Death anxiety among elderly people: role of gender, spirituality and mental health

DOAJ (DOAJ: Directory of Open Access Journals) · 11 citationsread the source →