Search the source libraries

Targeted client communication via mobile devices for improving sexual and reproductive health.

Background: The burden of poor sexual and reproductive health (SRH) worldwide is substantial, disproportionately affecting those living in low- and middle-income countries. Targeted client communication (TCC) delivered via mobile devices (MD) (TCCMD) may improve the health behaviours and service use important for sexual and reproductive health. Objectives: To assess the effects of TCC via MD on adolescents' knowledge, and on adolescents' and adults' sexual and reproductive health behaviour, health service use, and health and well-being. Search methods: In July/August 2017, we searched five databases including The Cochrane Central Register of Controlled Trials, MEDLINE and Embase. We also searched two trial registries. A search update was carried out in July 2019 and potentially relevant studies are awaiting classification. Selection criteria: We included randomised controlled trials of TCC via MD to improve sexual and reproductive health behaviour, health service use, and health and well-being. Eligible comparators were standard care or no intervention, non-digital TCC, and digital non-targeted communication. Data collection and analysis: We used standard methodological procedures recommended by Cochrane, although data extraction and risk of bias assessments were carried out by one person only and cross-checked by a second. We have presented results separately for adult and adolescent populations, and for each comparison. Main results: We included 40 trials (27 among adult populations and 13 among adolescent populations) with a total of 26,854 participants. All but one of the trials among adolescent populations were conducted in high-income countries. Trials among adult populations were conducted in a range of high- to low-income countries. Among adolescents, nine interventions were delivered solely through text messages; four interventions tested text messages in combination with another communication channel, such as emails, multimedia messaging, or voice calls; and one intervention used voice calls alone. Among adults, 20 interventions were delivered through text messages; two through a combination of text messages and voice calls; and the rest were delivered through other channels such as voice calls, multimedia messaging, interactive voice response, and instant messaging services. Adolescent populations TCCMD versus standard care TCCMD may increase sexual health knowledge (risk ratio (RR) 1.45, 95% confidence interval (CI) 1.23 to 1.71; low-certainty evidence). TCCMD may modestly increase contraception use (RR 1.19, 95% CI 1.05 to 1.35; low-certainty evidence). The effects on condom use, antiretroviral therapy (ART) adherence, and health service use are uncertain due to very low-certainty evidence. The effects on abortion and STI rates are unknown due to lack of studies. TCCMD versus non-digital TCC (e.g. pamphlets) The effects of TCCMD on behaviour (contraception use, condom use, ART adherence), service use, health and wellbeing (abortion and STI rates) are unknown due to lack of studies for this comparison. TCCMD versus digital non-targeted communication The effects on sexual health knowledge, condom and contraceptive use are uncertain due to very low-certainty evidence. Interventions may increase health service use (attendance for STI/HIV testing, RR 1.61, 95% CI 1.08 to 2.40; low-certainty evidence). The intervention may be beneficial for reducing STI rates (RR 0.61, 95% CI 0.28 to 1.33; low-certainty evidence), but the confidence interval encompasses both benefit and harm. The effects on abortion rates and on ART adherence are unknown due to lack of studies. We are uncertain whether TCCMD results in unintended consequences due to lack of evidence. Adult populations TCCMD versus standard care For health behaviours, TCCMD may modestly increase contraception use at 12 months (RR 1.17, 95% CI 0.92 to 1.48) and may reduce repeat abortion (RR 0.68 95% CI 0.28 to 1.66), though the confidence interval encompasses benefit and harm (low-certainty evidence). The effect on condom use is uncertain. No study measured the impact of this intervention on STI rates. TCCMD may modestly increase ART adherence (RR 1.13, 95% CI 0.97 to 1.32, low-certainty evidence, and standardised mean difference 0.44, 95% CI -0.14 to 1.02, low-certainty evidence). TCCMD may modestly increase health service utilisation (RR 1.17, 95% CI 1.04 to 1.31; low-certainty evidence), but there was substantial heterogeneity (I2 = 85%), with mixed results according to type of service utilisation (i.e. attendance for STI testing; HIV treatment; voluntary male medical circumcision (VMMC); VMMC post-operative visit; post-abortion care). For health and well-being outcomes, there may be little or no effect on CD4 count (mean difference 13.99, 95% CI -8.65 to 36.63; low-certainty evidence) and a slight reduction in virological failure (RR 0.86, 95% CI 0.73 to 1.01; low-certainty evidence). TCCMD versus non-digital TCC No studies reported STI rates, condom use, ART adherence, abortion rates, or contraceptive use as outcomes for this comparison. TCCMD may modestly increase in service attendance overall (RR: 1.12, 95% CI 0.92-1.35, low certainty evidence), however the confidence interval encompasses benefit and harm. TCCMD versus digital non-targeted communication No studies reported STI rates, condom use, ART adherence, abortion rates, or contraceptive use as outcomes for this comparison. TCCMD may increase service utilisation overall (RR: 1.71, 95% CI 0.67-4.38, low certainty evidence), however the confidence interval encompasses benefit and harm and there was considerable heterogeneity (I2 = 72%), with mixed results according to type of service utilisation (STI/HIV testing, and VMMC). Few studies reported on unintended consequences. One study reported that a participant withdrew from the intervention as they felt it compromised their undisclosed HIV status. Authors' conclusions: TCCMD may improve some outcomes but the evidence is of low certainty. The effect on most outcomes is uncertain/unknown due to very low certainty evidence or lack of evidence. High quality, adequately powered trials and cost effectiveness analyses are required to reliably ascertain the effects and relative benefits of TCC delivered by mobile devices. Given the sensitivity and stigma associated with sexual and reproductive health future studies should measure unintended consequences, such as partner violence or breaches of confidentiality.

The Cochrane database of systematic reviews · meta-analysis · 32 citationsread the source →

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 →

Integrated weight loss and cognitive behavioural therapy (CBT) for the treatment of recurrent binge eating and high body mass index: a randomized controlled trial.

Purpose: The association between binge eating and obesity is increasing. Treatments for disorders of recurrent binge eating comorbid with obesity reduce eating disorder (ED) symptoms, but not weight. This study investigated the efficacy and safety of introducing a weight loss intervention to the treatment of people with disorders of recurrent binge eating and a high body mass index (BMI). Methods: A single-blind randomized controlled trial selected adults with binge eating disorder or bulimia nervosa and BMI ≥ 27 to < 40 kg/m2. The primary outcome was sustained weight loss at 12-month follow-up. Secondary outcomes included ED symptoms. Mixed effects models analyses were conducted using multiple imputed datasets in the presence of missing data. Results: Ninety-eight participants were randomized to the Health Approach to Weight Management and Food in Eating Disorders (HAPIFED) or to the Cognitive Behavioural Therapy-Enhanced (CBT-E). No between-group differences were found for percentage of participants achieving weight loss or secondary outcomes, except for reduction of purging behaviour, which was greater with HAPIFED (p = 0.016). Binge remission rates specifically at 12-month follow-up favoured HAPIFED (34.0% vs 16.7%; p = 0.049). Overall, significant improvements in the reduction of ED symptoms were seen in both groups and these were sustained at the 12-month follow-up. Conclusion: HAPIFED was not superior to CBT-E in promoting clinically significant weight loss and was not significantly different in reducing most ED symptoms. No harm was observed with HAPIFED, in that no worsening of ED symptoms was observed. Further studies should test approaches that target both the management of ED symptoms and the high BMI. Level of evidence: Level I, randomized controlled trial TRIAL REGISTRATION: US National Institutes of Health clinical trial registration number NCT02464345, date of registration 1 June 2015.

Eating and weight disorders : EWD · randomised controlled trial · 23 citationsread the source →

Comparing cognitive behavioural therapy for eating disorders integrated with behavioural weight loss therapy to cognitive behavioural therapy-enhanced alone in overweight or obese people with bulimia nervosa or binge eating disorder: study protocol for a randomised controlled trial.

Background: Around 40 % of individuals with eating disorders of recurrent binge eating, namely bulimia nervosa and binge eating disorder, are obese. In contrast to binge eating disorder, currently there is no evidence base for weight management or weight loss psychological therapies in the treatment of bulimia nervosa despite their efficacy in binge eating disorder. Thus, a manualised therapy called HAPIFED (Healthy APproach to weIght management and Food in Eating Disorders) has been developed. HAPIFED integrates the leading evidence-based psychological therapies, cognitive behavioural therapy-enhanced (CBT-E) and behavioural weight loss treatment (BWLT) for binge eating disorder and obesity respectively. The aim of the present study is to detail the protocol for a randomised controlled trial (RCT) of HAPIFED versus CBT-E for people with bulimia nervosa and binge eating disorder who are overweight/obese. Method/design: A single-blind superiority RCT is proposed. One hundred Brazilian participants aged ≥ 18 years, with a diagnosis of bulimia nervosa or binge eating disorder, BMI > 27 to < 40 kg/m(2), will be recruited from both community and clinics and individually randomised to a therapy arm. Five groups of ten participants will receive the experimental intervention (HAPIFED) and the other five groups of ten the control intervention (CBT-E). Both therapies are manualised, and in this RCT will comprise 1 individual session and 29 office-based group sessions over 6 months. Assessment points will be at baseline, end of therapy, and 6 and 12 months after end of therapy. The primary outcome of this intervention will be reduced weight. Secondary outcomes will be improved metabolic indicators of weight management, reduction in eating disorder symptoms including improved control over eating, improved adaptive function, physical and mental health-related quality of life, and reduced levels of depression and anxiety. Discussion: This study will be the first to investigate a psychological therapy that aims to assist weight management in people with co-morbid overweight or obesity bulimia nervosa as well as with binge eating disorder. It will have the potential to improve health outcomes for the rapidly increasing number of adults with co-morbid obesity and binge eating disorder or bulimia nervosa. Trial registration: US National Institutes of Health clinical trial registration number NCT02464345 , date of registration 1 June 2015.

Trials · randomised controlled trial · 21 citationsread the source →

Effects of a parenting intervention to address maternal psychological wellbeing and child development and growth in rural Uganda: a community-based, cluster randomised trial.

Background: Parenting interventions have been implemented to improve the compromised developmental potential among 39% of children younger than 5 years living in low-income and middle-income countries. Maternal wellbeing is important for child development, especially in children younger than 3 years who are vulnerable and dependent on their mothers for nutrition and stimulation. We assessed an integrated, community-based parenting intervention that targeted both child development and maternal wellbeing in rural Uganda. Methods: In this community-based, cluster randomised trial, we assessed the effectiveness of a manualised, parenting intervention in Lira, Uganda. We selected and randomly assigned 12 parishes (1:1) to either parenting intervention or control (inclusion on a waitlist with a brief message on nutrition) groups using a computer-generated list of random numbers. Within each parish, we selected two to three eligible communities that had a parish office or a primary school in which a preschool could be established, more than 75 households with children younger than 6 years, and at least 15 socially disadvantaged families (ie, maternal education of primary school level or lower) with at least one child younger than 36 months. Participants within communities were mother-child dyads, where the child was 12-36 months of age at enrollment, and the mother had low maternal education. In the parenting intervention group, participants attended 12 fortnightly peer-led group sessions focusing on child care and maternal wellbeing. The primary outcomes were cognitive and receptive language development, as measured with the Bayley Scales of Infant Development, 3rd edn. Secondary outcomes included self-reported maternal depressive symptoms, using the Center for Epidemiologic Studies Depression Scale, and child growth. Theoretically-relevant parenting practices, including the Home Observation for Measurement of the Environment inventory, and mother-care variables, such as perceived spousal support, were also assessed as potential mediators. Baseline assessments were done in January, 2013, and endline assessments were done in November, 2013, 3 months after completion of the programme. Ethics approval was received from Mbarara and McGill universities. This trial is registered with ClinicalTrials.gov, NCT01906606. Findings: Between December, 2012, and January, 2013, 13 communities (194 dyads) were randomly assigned to receive intervention, and 12 communities (154 dyads) were assigned to a waitlist control. 319 dyads completed baseline measures (171 in the intervention group and 148 in the control group), and 291 dyads completed endline measures (160 in the intervention group and 131 in the control group). At endline, children in the intervention group had significantly higher cognitive scores (58·90 vs 55·65, effect size 0·36, 95% CI 0·12-0·59) and receptive language scores (23·86 vs 22·40, 0·27, 0·03-0·50) than did children in the control group. Mothers in the intervention group reported significantly fewer depressive symptoms (15·36 vs 18·61, -0·391, 95% CI -0·62 to -0·16) than did mothers in the control group. However, no differences were found in child growth between groups. Interpretation: The 12 session integrated parenting intervention delivered by non-professional community members improved child development and maternal wellbeing in rural Uganda. Because this intervention was largely managed and implemented by a local organisation, using local community members and minimal resources, such a programme has the potential to be replicated and scaled up in other low-resource, village-based settings. Funding: Plan Uganda via Plan Finland (Ministry of Foreign Affairs) and Plan Australia (Australian Aid).

The Lancet. Global health · randomised controlled trial · 208 citationsread the source →

Artificial Intelligence-Based Chatbots for Promoting Health Behavioral Changes: Systematic Review.

Background: Artificial intelligence (AI)-based chatbots can offer personalized, engaging, and on-demand health promotion interventions. Objective: The aim of this systematic review was to evaluate the feasibility, efficacy, and intervention characteristics of AI chatbots for promoting health behavior change. Methods: A comprehensive search was conducted in 7 bibliographic databases (PubMed, IEEE Xplore, ACM Digital Library, PsycINFO, Web of Science, Embase, and JMIR publications) for empirical articles published from 1980 to 2022 that evaluated the feasibility or efficacy of AI chatbots for behavior change. The screening, extraction, and analysis of the identified articles were performed by following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Results: Of the 15 included studies, several demonstrated the high efficacy of AI chatbots in promoting healthy lifestyles (n=6, 40%), smoking cessation (n=4, 27%), treatment or medication adherence (n=2, 13%), and reduction in substance misuse (n=1, 7%). However, there were mixed results regarding feasibility, acceptability, and usability. Selected behavior change theories and expert consultation were used to develop the behavior change strategies of AI chatbots, including goal setting, monitoring, real-time reinforcement or feedback, and on-demand support. Real-time user-chatbot interaction data, such as user preferences and behavioral performance, were collected on the chatbot platform to identify ways of providing personalized services. The AI chatbots demonstrated potential for scalability by deployment through accessible devices and platforms (eg, smartphones and Facebook Messenger). The participants also reported that AI chatbots offered a nonjudgmental space for communicating sensitive information. However, the reported results need to be interpreted with caution because of the moderate to high risk of internal validity, insufficient description of AI techniques, and limitation for generalizability. Conclusions: AI chatbots have demonstrated the efficacy of health behavior change interventions among large and diverse populations; however, future studies need to adopt robust randomized control trials to establish definitive conclusions.

Journal of medical Internet research · systematic review · 309 citationsread the source →

Empowering consumers to PREVENT diet-related diseases through OMICS sciences (PREVENTOMICS): protocol for a parallel double-blinded randomised intervention trial to investigate biomarker-based nutrition plans for weight loss.

Introduction: Personalised nutrition holds immense potential over conventional one-size-fits-all approaches for preventing and treating diet-related diseases, such as obesity. The current study aims to examine whether a personalised nutritional plan produces more favourable health outcomes than a standard approach based on general dietary recommendations in subjects with overweight or obesity and elevated waist circumference. Methods and analysis: This project is a 10-week parallel, double-blinded randomised intervention trial. We plan to include 100 adults aged 18-65 years interested in losing weight, with body mass index ≥27 but<40 kg/m2 and elevated waist circumference (males >94 cm; females >80 cm). Participants will be categorised into one of five predefined 'clusters' based on their individual metabolic biomarker profile and genetic background, and will be randomised in a 1:1 ratio to one of two groups: (1) personalised plan group that will receive cluster-specific meals every day for 6 days a week, in conjunction with a personalised behavioural change programme via electronic push notifications; or (2) control group that will receive meals following the general dietary recommendations in conjunction with generic health behaviour prompts. The primary outcome is the difference between groups (personalised vs control) in the change in fat mass from baseline. Secondary outcomes include changes in weight and body composition, fasting blood glucose and insulin, lipid profile, adipokines, inflammatory biomarkers, and blood pressure. Other outcomes involve measures of physical activity and sleep patterns, health-related quality of life, dietary intake, eating behaviour, and biomarkers of food intake. The effect of the intervention on the primary outcome will be analysed by means of linear mixed models. Ethics and dissemination: The protocol has been approved by the Ethics Committee of the Capital Region, Copenhagen, Denmark. Study findings will be disseminated through peer-reviewed publications, conference presentations and media outlets. Trial registration number: NCT04590989.

BMJ open · clinical trial · 18 citationsread the source →

Early palliative care for patients with advanced cancer: a cluster-randomised controlled trial.

Background: Patients with advanced cancer have reduced quality of life, which tends to worsen towards the end of life. We assessed the effect of early palliative care in patients with advanced cancer on several aspects of quality of life. Methods: The study took place at the Princess Margaret Cancer Centre (Toronto, ON, Canada), between Dec 1, 2006, and Feb 28, 2011. 24 medical oncology clinics were cluster randomised (in a 1:1 ratio, using a computer-generated sequence, stratified by clinic size and tumour site [four lung, eight gastrointestinal, four genitourinary, six breast, two gynaecological]), to consultation and follow-up (at least monthly) by a palliative care team or to standard cancer care. Complete masking of interventions was not possible; however, patients provided written informed consent to participate in their own study group, without being informed of the existence of another group. Eligible patients had advanced cancer, European Cooperative Oncology Group performance status of 0-2, and a clinical prognosis of 6-24 months. Quality of life (Functional Assessment of Chronic Illness Therapy--Spiritual Well-Being [FACIT-Sp] scale and Quality of Life at the End of Life [QUAL-E] scale), symptom severity (Edmonton Symptom Assessment System [ESAS]), satisfaction with care (FAMCARE-P16), and problems with medical interactions (Cancer Rehabilitation Evaluation System Medical Interaction Subscale [CARES-MIS]) were measured at baseline and monthly for 4 months. The primary outcome was change score for FACIT-Sp at 3 months. Secondary endpoints included change score for FACIT-Sp at 4 months and change scores for other scales at 3 and 4 months. This trial is registered with ClinicalTrials.gov, number NCT01248624. Findings: 461 patients completed baseline measures (228 intervention, 233 control); 393 completed at least one follow-up assessment. At 3-months, there was a non-significant difference in change score for FACIT-Sp between intervention and control groups (3·56 points [95% CI -0·27 to 7·40], p=0·07), a significant difference in QUAL-E (2·25 [0·01 to 4·49], p=0·05) and FAMCARE-P16 (3·79 [1·74 to 5·85], p=0·0003), and no difference in ESAS (-1·70 [-5·26 to 1·87], p=0·33) or CARES-MIS (-0·66 [-2·25 to 0·94], p=0·40). At 4 months, there were significant differences in change scores for all outcomes except CARES-MIS. All differences favoured the intervention group. Interpretation: Although the difference in quality of life was non-significant at the primary endpoint, this trial shows promising findings that support early palliative care for patients with advanced cancer. Funding: Canadian Cancer Society, Ontario Ministry of Health and Long Term Care.

Lancet (London, England) · randomised controlled trial · 1215 citationsread the source →

Parent Perceptions of Infant Symptoms and Suffering and Associations With Distress Among Bereaved Parents in the NICU.

Context: Healthcare providers and parents face many challenges caring for infants at the end of life (EOL). Symptom assessment and management in critically ill infants can be especially difficult. However, the impact of the infant's EOL experience on bereaved parents is largely unknown. Objective: Explore associations between parental perceptions of infant symptoms and suffering at EOL in the neonatal intensive care unit (NICU) and parent adjustment following the death. Methods: Retrospective, cross-sectional pilot study involving parents of infants who died within the previous five years in a large, Midwestern, level IV NICU. Parents were recruited through mailed invitations, and 40 mothers and 27 fathers participated from 40 families. Parents retrospectively reported on infant symptom burden and suffering during the last week of life and the Impact of Events Scale-Revised (IES-R), and Prolonged Grief-13 (PG-13). Hierarchical regressions examined demographic/medical factors and parent perceptions at EOL in relation to post-traumatic stress symptoms (PTSS) and prolonged grief (PG). Results: Clinical levels of PTSS (Mothers = 18%; Fathers = 11%) and PG (Mothers and Fathers = 3%) were low. Maternal perception of higher symptom burden was associated with greater PTSS, R2 = 0.46, P= 0.001, and PG, R2 = 0.47, P < 0.01. Paternal perception of greater infant suffering was associated with greater PTSS, R2 = 0.48, P= 0.001, and PG, R2 = .38, P < 0.01. Conclusion: Perceptions of symptoms and suffering were associated differently with mother and father adjustment after bereavement. While not necessarily causal, better symptom management at EOL could minimize distress for both infants and their parents.

Journal of pain and symptom management · 22 citationsread the source →

Physical activity and likelihood of depression in adults: a review.

Objective: This review examines original research which has investigated associations between physical activity (PA) dose (i.e. frequency, intensity and duration) and domain and depression or symptoms of depression in adults. Methods: A search of electronic databases and authors' own bibliographic libraries was performed between 2006 and 2007 for original research articles investigating associations between PA and depression in adults. A total of 27 observational and 40 intervention studies were included. Results: Of the studies that focused on the association between duration of PA and likelihood of depression, all five observational studies, and five of the seven intervention studies found both shorter and longer durations of PA were associated with reduced likelihood of depression. Of the studies that focused on the association between intensity of PA and likelihood of depression, four of the six observational studies found that vigorous-intensity PA was more strongly associated with decreased likelihood of depression than lower intensities. Most intervention studies showed that both intensities were effective in reducing the likelihood of depression. Two observational studies found a stronger inverse relationship of leisure-time PA with depression than PA in other domains. There is insufficient evidence regarding the importance of the PA setting on depression. Conclusion: Although the dose and domain of physical activity varied across studies reviewed, evidence suggests that even low doses of PA may be protective against depression. Further studies examining the optimal domain of PA for reducing the likelihood of depression are needed.

Preventive medicine · review · 403 citationsread the source →

Dropouts versus completers among chronically depressed outpatients.

Background: Premature termination is common among patients treated for depression with either pharmacotherapy or psychotherapy. Yet little is known about factors associated with premature treatment termination among depressed patients. Methods: This study examines predictors of, time to, and reasons for dropout from the 12-week acute phase treatment of nonpsychotic adult outpatients, age 18-75, with chronic major depression who were randomly assigned to nefazadone alone (MED), cognitive behavioral analysis system of psychotherapy alone (CBASP) or both treatments (COMB). Results: Of 681 randomized study participants, 156 were defined as dropouts. Dropout rates were equivalent across the three treatments. Among dropouts, those in COMB remained in treatment (Mean=40 days) significantly longer than those in either MED (Mean=27 days) or CBASP (Mean=28 days). Dropouts attributed to medication side-effects were significantly lower in COMB than in MED, suggesting that the relationship with the psychotherapist may increase patient willingness to tolerate side-effects associated with antidepressant medications. Ethnic or racial minority status, younger age, lower income, and co-morbid anxiety disorders significantly predicted dropout in the full sample. Within treatments, differences between completers and dropouts in minority status and the prevalence of anxiety disorders were most pronounced in MED. Among those receiving CBASP, dropouts had significantly lower therapeutic alliance scores than completers. Limitations: The sample included only individuals with chronic depression. Conclusions: Predictors of dropout included baseline patient characteristics, but not early response to treatment. Ethnic and racial minorities and those with comorbid anxiety are at higher risk of premature termination, particularly in pharmacotherapy, and may require modified treatment strategies.

Journal of affective disorders · randomised controlled trial · 94 citationsread the source →

Prevalence of psychological morbidities among general population, healthcare workers and COVID-19 patients amidst the COVID-19 pandemic: A systematic review and meta-analysis.

This review was done to synthesize the existing evidence on the prevalence of various psychological morbidities among general public, healthcare workers and COVID-19 patients amidst this pandemic situation. Systematic searches were conducted in various databases and search engines such as Medline, Chinese national knowledge infrastructure, Cochrane library, ScienceDirect, and Google Scholar from inception until 22 April 2020. Newcastle Ottawa scale was used to assess the quality of included studies. We carried out a meta-analysis with random-effects model and reported pooled prevalence with 95% confidence intervals (CIs).A total of 50 studies were included in the review. Only seven studies (14%) had low risk of bias. Pooled prevalence rate of psychological morbidities includes poor sleep quality (40%), stress (34%), psychological distress (34%), insomnia (30%), post-traumatic stress symptoms (27%), anxiety (26%), depression (26%). Pooled prevalence rate of psychological morbidities with respect to impact of event due to COVID-19 pandemic was 44% (95%CI-42% to 47%). The burden of these psychological morbidities was highest among the COVID-19 patients followed by healthcare workers and general population.

Psychiatry research · meta-analysis · 355 citationsread the source →

Water intake, hydration status and 2-year changes in cognitive performance: a prospective cohort study.

Background: Water intake and hydration status have been suggested to impact cognition; however, longitudinal evidence is limited and often inconsistent. This study aimed to longitudinally assess the association between hydration status and water intake based on current recommendations, with changes in cognition in an older Spanish population at high cardiovascular disease risk. Methods: A prospective analysis was conducted of a cohort of 1957 adults (aged 55-75) with overweight/obesity (BMI between ≥ 27 and < 40 kg/m2) and metabolic syndrome from the PREDIMED-Plus study. Participants had completed bloodwork and validated, semiquantitative beverage and food frequency questionnaires at baseline, as well as an extensive neuropsychological battery of 8 validated tests at baseline and 2 years of follow-up. Hydration status was determined by serum osmolarity calculation and categorized as < 295 mmol/L (hydrated), 295-299.9 mmol/L (impending dehydration), and ≥ 300 mmol/L (dehydrated). Water intake was assessed as total drinking water intake and total water intake from food and beverages and according to EFSA recommendations. Global cognitive function was determined as a composite z-score summarizing individual participant results from all neuropsychological tests. Multivariable linear regression models were fitted to assess the associations between baseline hydration status and fluid intake, continuously and categorically, with 2-year changes in cognitive performance. Results: The mean baseline daily total water intake was 2871 ± 676 mL/day (2889 ± 677 mL/day in men; 2854 ± 674 mL/day in women), and 80.2% of participants met the ESFA reference values for an adequate intake. Serum osmolarity (mean 298 ± 24 mmol/L, range 263 to 347 mmol/L) indicated that 56% of participants were physiologically dehydrated. Lower physiological hydration status (i.e., greater serum osmolarity) was associated with a greater decline in global cognitive function z-score over a 2-year period (β: - 0.010; 95% CI - 0.017 to - 0.004, p-value = 0.002). No significant associations were observed between water intake from beverages and/or foods with 2-year changes in global cognitive function. Conclusions: Reduced physiological hydration status was associated with greater reductions in global cognitive function over a 2-year period in older adults with metabolic syndrome and overweight or obesity. Future research assessing the impact of hydration on cognitive performance over a longer duration is needed. Trial registration: International Standard Randomized Controlled Trial Registry, ISRCTN89898870. Retrospectively registered on 24 July 2014.

BMC medicine · 32 citationsread the source →

The effectiveness of community engagement in public health interventions for disadvantaged groups: a meta-analysis.

Background: Inequalities in health are acknowledged in many developed countries, whereby disadvantaged groups systematically suffer from worse health outcomes such as lower life expectancy than non-disadvantaged groups. Engaging members of disadvantaged communities in public health initiatives has been suggested as a way to reduce health inequities. This systematic review was conducted to evaluate the effectiveness of public health interventions that engage the community on a range of health outcomes across diverse health issues. Methods: We searched the following sources for systematic reviews of public health interventions: Cochrane CDSR and CENTRAL, Campbell Library, DARE, NIHR HTA programme website, HTA database, and DoPHER. Through the identified reviews, we collated a database of primary studies that appeared to be relevant, and screened the full-text documents of those primary studies against our inclusion criteria. In parallel, we searched the NHS EED and TRoPHI databases for additional primary studies. For the purposes of these analyses, study design was limited to randomised and non-randomised controlled trials. Only interventions conducted in OECD countries and published since 1990 were included. We conducted a random effects meta-analysis of health behaviour, health consequences, self-efficacy, and social support outcomes, and a narrative summary of community outcomes. We tested a range of moderator variables, with a particular emphasis on the model of community engagement used as a potential moderator of intervention effectiveness. Results: Of the 9,467 primary studies scanned, we identified 131 for inclusion in the meta-analysis. The overall effect size for health behaviour outcomes is d = .33 (95% CI .26, .40). The interventions were also effective in increasing health consequences (d = .16, 95% CI .06, .27); health behaviour self-efficacy (d = .41, 95% CI .16, .65) and perceived social support (d = .41, 95% CI .23, .65). Although the type of community engagement was not a significant moderator of effect, we identified some trends across studies. Conclusions: There is solid evidence that community engagement interventions have a positive impact on a range of health outcomes across various conditions. There is insufficient evidence to determine whether one particular model of community engagement is more effective than any other.

BMC public health · meta-analysis · 351 citationsread the source →

The feasibility of progressive resistance training in women with polycystic ovary syndrome: a pilot randomized controlled trial.

Background: To evaluate the feasibility of executing a randomized controlled trial of progressive resistance training (PRT) in women with polycystic ovary syndrome (PCOS). Methods: Women with PCOS were randomized to an experimental (PRT) group or a no-exercise (usual care) control group. The PRT group was prescribed two supervised and two unsupervised (home-based) training sessions per week for 12 weeks. Feasibility outcomes included recruitment and attrition, adherence, adverse events, and completion of assessments. Secondary outcomes, collected pre and post intervention, included a range of pertinent physiological, functional and psychological measures. Results: Fifteen participants were randomised into the PRT group (n = 8) or control group (n = 7); five women (n = 2 in PRT group and n = 3 in control group) withdrew from the study. The most successful recruitment sources were Facebook (40 %) and online advertisement (27 %), while least successful methods were referrals by clinicians, colleagues and flyers. In the PRT group, attendance to supervised sessions was higher (95 %; standard deviation ±6 %) compared to unsupervised sessions (51 %; standard deviation ±28 %). No adverse events were attributed to PRT. Change in menstrual cycle status was not significantly different between groups over time (p = 0.503). However, the PRT group significantly increased body weight (p = 0.01), BMI (p = 0.04), lean mass (p = 0.01), fat-free mass (p = 0.005) and lower body strength (p = 0.03), while reducing waist circumference (p = 0.03) and HbA1c (p = 0.033) versus the control group. The PRT group also significantly improved across several domains of disease-specific and general health-related quality of life, depression, anxiety and exercise self-efficacy. Conclusion: A randomized controlled trial of PRT in PCOS would be feasible, and this mode of exercise may elicit a therapeutic effect on clinically important outcomes in this cohort. The success of a large-scale trial required to confirm these findings would be contingent on addressing the feasibility hurdles identified in this study with respect to recruitment, attrition, compliance, and collection of standardized clinical data. Trial registration: Australia New Zealand Clinical Trials Registry; ACTRN12614000517673 Registered 15 May 2014.

BMC sports science, medicine & rehabilitation · 44 citationsread the source →

Sleep interventions for osteoarthritis and spinal pain: a systematic review and meta-analysis of randomized controlled trials.

Objectives: To determine if sleep interventions improve pain and sleep in people with osteoarthritis (OA) and/or spinal pain compared to control/placebo. Design: Medline, Embase, AMED, PsycINFO, CENTRAL, CINAHL and PEDro were searched from their inception date to July 2017. Keywords relating to "sleep", "OA", "spinal pain", and "randomized controlled trial (RCT)" were combined. Included RCTs investigated the use of sleep interventions for people with OA and/or spinal pain, and measured at least one sleep and health related outcome. Meta-analyses were performed to pool mean differences for pain and sleep quality. Prospero: CRD42016036315. Results: Of 1445 unique records, 24 studies were included. Sixteen studies included participants with spinal pain, seven with OA, and one included a mixed population. Sleep interventions included established sleep interventions (ESI) [cognitive behavioural therapy (CBT) and pharmacological interventions], and a range of others. Intervention periods ranged from 4 to 10 weeks. Thirteen studies were of moderate to high quality (PEDro ≥ 6/10). Due to high heterogeneity between studies we also performed sub-group and sensitivity analyses. ESI decreased Insomnia Severity Index (ISI) for people with low back pain (LBP) (pooled mean difference: -6.78/28, 95% confidence interval (95% CI): [-9.47, -4.09], I2 = 40%) and OA (-2.41, [-4.19, -0.63], 0%). However ESI decreased pain for people with LBP (pooled mean difference: visual analogue scale (VAS) -12.77/100, 95% CI: [-17.57, -7.97], I2 = 0%), but not OA (-2.32, [-7.18, 2.54], 27%). Conclusion: ESI appeared to improve sleep and pain for people with LBP, and sleep for people with OA. However more vigorous studies need to be conducted.

Osteoarthritis and cartilage · meta-analysis · 41 citationsread the source →

Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic.

Background: Before the COVID-19 pandemic, coronaviruses caused two noteworthy outbreaks: severe acute respiratory syndrome (SARS), starting in 2002, and Middle East respiratory syndrome (MERS), starting in 2012. We aimed to assess the psychiatric and neuropsychiatric presentations of SARS, MERS, and COVID-19. Methods: In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases (from their inception until March 18, 2020), and medRxiv, bioRxiv, and PsyArXiv (between Jan 1, 2020, and April 10, 2020) were searched by two independent researchers for all English-language studies or preprints reporting data on the psychiatric and neuropsychiatric presentations of individuals with suspected or laboratory-confirmed coronavirus infection (SARS coronavirus, MERS coronavirus, or SARS coronavirus 2). We excluded studies limited to neurological complications without specified neuropsychiatric presentations and those investigating the indirect effects of coronavirus infections on the mental health of people who are not infected, such as those mediated through physical distancing measures such as self-isolation or quarantine. Outcomes were psychiatric signs or symptoms; symptom severity; diagnoses based on ICD-10, DSM-IV, or the Chinese Classification of Mental Disorders (third edition) or psychometric scales; quality of life; and employment. Both the systematic review and the meta-analysis stratified outcomes across illness stages (acute vs post-illness) for SARS and MERS. We used a random-effects model for the meta-analysis, and the meta-analytical effect size was prevalence for relevant outcomes, I2 statistics, and assessment of study quality. Findings: 1963 studies and 87 preprints were identified by the systematic search, of which 65 peer-reviewed studies and seven preprints met inclusion criteria. The number of coronavirus cases of the included studies was 3559, ranging from 1 to 997, and the mean age of participants in studies ranged from 12·2 years (SD 4·1) to 68·0 years (single case report). Studies were from China, Hong Kong, South Korea, Canada, Saudi Arabia, France, Japan, Singapore, the UK, and the USA. Follow-up time for the post-illness studies varied between 60 days and 12 years. The systematic review revealed that during the acute illness, common symptoms among patients admitted to hospital for SARS or MERS included confusion (36 [27·9%; 95% CI 20·5-36·0] of 129 patients), depressed mood (42 [32·6%; 24·7-40·9] of 129), anxiety (46 [35·7%; 27·6-44·2] of 129), impaired memory (44 [34·1%; 26·2-42·5] of 129), and insomnia (54 [41·9%; 22·5-50·5] of 129). Steroid-induced mania and psychosis were reported in 13 (0·7%) of 1744 patients with SARS in the acute stage in one study. In the post-illness stage, depressed mood (35 [10·5%; 95% CI 7·5-14·1] of 332 patients), insomnia (34 [12·1%; 8·6-16·3] of 280), anxiety (21 [12·3%; 7·7-17·7] of 171), irritability (28 [12·8%; 8·7-17·6] of 218), memory impairment (44 [18·9%; 14·1-24·2] of 233), fatigue (61 [19·3%; 15·1-23·9] of 316), and in one study traumatic memories (55 [30·4%; 23·9-37·3] of 181) and sleep disorder (14 [100·0%; 88·0-100·0] of 14) were frequently reported. The meta-analysis indicated that in the post-illness stage the point prevalence of post-traumatic stress disorder was 32·2% (95% CI 23·7-42·0; 121 of 402 cases from four studies), that of depression was 14·9% (12·1-18·2; 77 of 517 cases from five studies), and that of anxiety disorders was 14·8% (11·1-19·4; 42 of 284 cases from three studies). 446 (76·9%; 95% CI 68·1-84·6) of 580 patients from six studies had returned to work at a mean follow-up time of 35·3 months (SD 40·1). When data for patients with COVID-19 were examined (including preprint data), there was evidence for delirium (confusion in 26 [65%] of 40 intensive care unit patients and agitation in 40 [69%] of 58 intensive care unit patients in one study, and altered consciousness in 17 [21%] of 82 patients who subsequently died in another study). At discharge, 15 (33%) of 45 patients with COVID-19 who were assessed had a dysexecutive syndrome in one study. At the time of writing, there were two reports of hypoxic encephalopathy and one report of encephalitis. 68 (94%) of the 72 studies were of either low or medium quality. Interpretation: If infection with SARS-CoV-2 follows a similar course to that with SARS-CoV or MERS-CoV, most patients should recover without experiencing mental illness. SARS-CoV-2 might cause delirium in a significant proportion of patients in the acute stage. Clinicians should be aware of the possibility of depression, anxiety, fatigue, post-traumatic stress disorder, and rarer neuropsychiatric syndromes in the longer term. Funding: Wellcome Trust, UK National Institute for Health Research (NIHR), UK Medical Research Council, NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London.

The lancet. Psychiatry · meta-analysis · 1531 citationsread the source →

Social network interventions for health behaviours and outcomes: A systematic review and meta-analysis.

Background: There has been a growing interest in understanding the effects of social networks on health-related behaviour, with a particular backdrop being the emerging prominence of complexity or systems science in public health. Social network interventions specifically use or alter the characteristics of social networks to generate, accelerate, or maintain health behaviours. We conducted a systematic review and meta-analysis to investigate health behaviour outcomes of social network interventions. Methods and findings: We searched eight databases and two trial registries from 1990 to May 28, 2019, for English-language reports of randomised controlled trials (RCTs) and before-and-after studies investigating social network interventions for health behaviours and outcomes. Trials that did not specifically use social networks or that did not include a comparator group were excluded. We screened studies and extracted data from published reports independently. The primary outcome of health behaviours or outcomes at ≤6 months was assessed by random-effects meta-analysis. Secondary outcomes included those measures at >6-12 months and >12 months. This study is registered with the International Prospective Register of Systematic Reviews, PROSPERO: CRD42015023541. We identified 26,503 reports; after exclusion, 37 studies, conducted between 1996 and 2018 from 11 countries, were eligible for analysis, with a total of 53,891 participants (mean age 32.4 years [SD 12.7]; 45.5% females). A range of study designs were included: 27 used RCT/cluster RCT designs, and 10 used other study designs. Eligible studies addressed a variety of health outcomes, in particular sexual health and substance use. Social network interventions showed a significant intervention effect compared with comparator groups for sexual health outcomes. The pooled odds ratio (OR) was 1.46 (95% confidence interval [CI] 1.01-2.11; I2 = 76%) for sexual health outcomes at ≤6 months and OR 1.51 (95% CI 1.27-1.81; I2 = 40%) for sexual health outcomes at >6-12 months. Intervention effects for drug risk outcomes at each time point were not significant. There were also significant intervention effects for some other health outcomes including alcohol misuse, well-being, change in haemoglobin A1c (HbA1c), and smoking cessation. Because of clinical and measurement heterogeneity, it was not appropriate to pool data on these other behaviours in a meta-analysis. For sexual health outcomes, prespecified subgroup analyses were significant for intervention approach (p < 0.001), mean age of participants (p = 0.002), and intervention length (p = 0.05). Overall, 22 of the 37 studies demonstrated a high risk of bias, as measured by the Cochrane Risk of Bias tool. The main study limitations identified were the inclusion of studies of variable quality; difficulty in isolating the effects of specific social network intervention components on health outcomes, as interventions included other active components; and reliance on self-reported outcomes, which have inherent recall and desirability biases. Conclusions: Our findings suggest that social network interventions can be effective in the short term (<6 months) and longer term (>6 months) for sexual health outcomes. Intervention effects for drug risk outcomes at each time point were not significant. There were also significant intervention effects for some other health outcomes including alcohol misuse, well-being, change in HbA1c, and smoking cessation.

PLoS medicine · meta-analysis · 211 citationsread the source →

Mild dehydration impairs cognitive performance and mood of men.

The present study assessed the effects of mild dehydration on cognitive performance and mood of young males. A total of twenty-six men (age 20·0 (sd 0·3) years) participated in three randomised, single-blind, repeated-measures trials: exercise-induced dehydration plus a diuretic (DD; 40 mg furosemide); exercise-induced dehydration plus placebo containing no diuretic (DN); exercise while maintaining euhydration plus placebo (EU; control condition). Each trial included three 40 min treadmill walks at 5·6 km/h, 5 % grade in a 27·7°C environment. A comprehensive computerised six-task cognitive test battery, the profile of mood states questionnaire and the symptom questionnaire (headache, concentration and task difficulty) were administered during each trial. Paired t tests compared the DD and DN trials resulting in >1 % body mass loss (mean 1·59 (sd 0·42) %) with the volunteer's EU trial (0·01 (sd 0·03) %). Dehydration degraded specific aspects of cognitive performance: errors increased on visual vigilance (P = 0·048) and visual working memory response latency slowed (P = 0·021). Fatigue and tension/anxiety increased due to dehydration at rest (P = 0·040 and 0·029) and fatigue during exercise (P = 0·026). Plasma osmolality increased due to dehydration (P < 0·001) but resting gastrointestinal temperature was not altered (P = 0·238). In conclusion, mild dehydration without hyperthermia in men induced adverse changes in vigilance and working memory, and increased tension/anxiety and fatigue.

The British journal of nutrition · randomised controlled trial · 162 citationsread the source →

A clinical trial comparing trauma-informed guilt reduction therapy (TrIGR), a brief intervention for trauma-related guilt, to supportive care therapy.

Introduction: Trauma-related guilt is common, associated with posttraumatic mental health problems, and can persist after posttraumatic stress disorder (PTSD) treatment. We compared the efficacy of two six-session psychotherapies, Trauma-Informed Guilt Reduction (TrIGR) and Supportive Care Therapy (SCT), for reducing trauma-related guilt. TrIGR helps patients accurately appraise their role in the trauma and re-engage in values. In SCT, patients guide session content. Methods: A total of 184 veterans seeking VA mental health services were enrolled across two sites; 145 veterans (mean age: 39.2 [8.1]; 92.4% male; 84.8% with PTSD) who endorsed guilt related to a traumatic event that occurred during a post 9/11 Iraq or Afghanistan deployment were randomized and assessed at baseline, posttreatment, 3- and 6-month follow-up. Results: Linear mixed models using intent-to-treat analyses showed guilt decreased in both conditions with a greater decrease for TrIGR (treatment × time, -0.22; F 1, 455.2  = 18.49, p = .001; d = 0.92) than supportive therapy. PTSD and depressive symptoms showed the same pattern. TrIGR had significantly higher likelihood of PTSD treatment response (67% vs. 40%), loss of PTSD diagnosis (50% vs. 14%), and meaningful change in depression (54% vs. 27%) than supportive therapy. Psychological distress and trait shame improved in both conditions. Quality of life did not change. Conclusions: Targeting guilt appears to be an effective means for reducing posttraumatic symptoms and distress.

Depression and anxiety · randomised controlled trial · 30 citationsread the source →

Mental health care for unaccompanied young refugees in Germany through a stepped care approach versus enhanced usual care: a cluster-randomised hybrid effectiveness-implementation trial.

Background: Unaccompanied young refugees are a vulnerable group with high rates of post-traumatic stress symptoms (PTSS). Stepped care approaches are recommended as a potential treatment framework, but research on the effectiveness of these models remains scarce. We aimed to compare a stepped care approach for unaccompanied young refugees with enhanced usual care under real-world conditions. Methods: In this cluster-randomised controlled type I hybrid implementation-effectiveness trial, we compared two active conditions, BETTER CARE and enhanced usual care, for unaccompanied young refugees in child and youth welfare service (CYWS) facilities across seven states in Germany. Eligibility criteria included age 12-20 years; arrival in Germany as unaccompanied minors; asylum application or intention; in CYWS facility care at baseline; and at least one traumatic event reported. Masking of participants was not possible due to each CYWS facility being randomly assigned to a specific treatment arm. Additionally, although study personnel were not masked to the condition, all data were self-reported and study personnel remained masked to data entry. BETTER CARE was a stepped care approach consisting of screening, prevention (via the Mein Weg [My Way] group intervention), and trauma-focused cognitive behavioural therapy (TF-CBT). Enhanced usual care included screening and a corresponding treatment recommendation. Clusters comprised one CYWS facility and were stratified and randomly assigned (1:1) using permuted blocks. Self-report questionnaires were used to assess PTSS, depressive symptoms, anxiety symptoms, and quality of life at baseline, 6 months, and 12 months. The primary outcome was a reduction in PTSS, analysed with the Child and Adolescent Trauma Screen (CATS-2) score in the intention-to-treat sample (all randomly assigned participants). The study was preregistered in the German Clinical Trials Register (DRKS00017453). Findings: The study was conducted between Oct 14, 2019, and July 27, 2023. 58 (11%) of 525 eligible facilities, including 627 unaccompanied young refugees originating from 40 countries, decided to participate and were randomly assigned. The mean age of the participants was 16·7 years (SD 1·3), with 569 (91%) identifying as male, 53 (8%) as female, and five (1%) as gender diverse. Participants reported a mean of six traumatic events (SD 3·3). 270 (43%) unaccompanied young refugees had clinically elevated levels of PTSS, and 357 (57%) were below the clinical threshold for PTSS (based on CATS-2 scores). 12 months after random assignment, there was a significant between-groups change over time effect size for PTSS in favour of BETTER CARE in the intention-to-treat sample (d=-0·17 [95% CI -0·34 to -0·004]). The dropout rate at 12 months was 38% (n=124) in BETTER CARE and 43% (n=131) in enhanced usual care. Service use and retention were low within the 12-month study period. Interpretation: This study shows the effectiveness of a stepped care model including screening, prevention, and evidence-based interventions for unaccompanied young refugees in a high-income country. The potential benefit of screening and structured care recommendations was highlighted further by improvements in the enhanced usual care condition. Dropout rates were high but similar to those in previous studies with young refugees. Future studies should address demand-side barriers to improve service use and retention. Funding: German Federal Ministry of Education and Research.

The Lancet. Global health · randomised controlled trial · 1 citationsread the source →

Suicide prevention strategies revisited: 10-year systematic review.

Background: Many countries are developing suicide prevention strategies for which up-to-date, high-quality evidence is required. We present updated evidence for the effectiveness of suicide prevention interventions since 2005. Methods: We searched PubMed and the Cochrane Library using multiple terms related to suicide prevention for studies published between Jan 1, 2005, and Dec 31, 2014. We assessed seven interventions: public and physician education, media strategies, screening, restricting access to suicide means, treatments, and internet or hotline support. Data were extracted on primary outcomes of interest, namely suicidal behaviour (suicide, attempt, or ideation), and intermediate or secondary outcomes (treatment-seeking, identification of at-risk individuals, antidepressant prescription or use rates, or referrals). 18 suicide prevention experts from 13 European countries reviewed all articles and rated the strength of evidence using the Oxford criteria. Because the heterogeneity of populations and methodology did not permit formal meta-analysis, we present a narrative analysis. Findings: We identified 1797 studies, including 23 systematic reviews, 12 meta-analyses, 40 randomised controlled trials (RCTs), 67 cohort trials, and 22 ecological or population-based investigations. Evidence for restricting access to lethal means in prevention of suicide has strengthened since 2005, especially with regard to control of analgesics (overall decrease of 43% since 2005) and hot-spots for suicide by jumping (reduction of 86% since 2005, 79% to 91%). School-based awareness programmes have been shown to reduce suicide attempts (odds ratio [OR] 0·45, 95% CI 0·24-0·85; p=0·014) and suicidal ideation (0·5, 0·27-0·92; p=0·025). The anti-suicidal effects of clozapine and lithium have been substantiated, but might be less specific than previously thought. Effective pharmacological and psychological treatments of depression are important in prevention. Insufficient evidence exists to assess the possible benefits for suicide prevention of screening in primary care, in general public education and media guidelines. Other approaches that need further investigation include gatekeeper training, education of physicians, and internet and helpline support. The paucity of RCTs is a major limitation in the evaluation of preventive interventions. Interpretation: In the quest for effective suicide prevention initiatives, no single strategy clearly stands above the others. Combinations of evidence-based strategies at the individual level and the population level should be assessed with robust research designs. Funding: The Expert Platform on Mental Health, Focus on Depression, and the European College of Neuropsychopharmacology.

The lancet. Psychiatry · systematic review · 1070 citationsread the source →

Populations and Interventions for Palliative and End-of-Life Care: A Systematic Review.

Importance: Evidence supports palliative care effectiveness. Given workforce constraints and the costs of new services, payers and providers need help to prioritize their investments. They need to know which patients to target, which personnel to hire, and which services best improve outcomes. Objective: To inform how payers and providers should identify patients with "advanced illness" and the specific interventions they should implement, we reviewed the evidence to identify (1) individuals appropriate for palliative care and (2) elements of health service interventions (personnel involved, use of multidisciplinary teams, and settings of care) effective in achieving better outcomes for patients, caregivers, and the healthcare system. Evidence review: Systematic searches of MEDLINE, EMBASE, PsycINFO, Web of Science, and Cochrane Database of Systematic Reviews databases (1/1/2001-1/8/2015). Results: Randomized controlled trials (124) met inclusion criteria. The majority of studies in cancer (49%, 38 of 77 studies) demonstrated statistically significant patient or caregiver outcomes (e.g., p < 0.05), as did those in congestive heart failure (CHF) (62%, 13 of 21), chronic obstructive pulmonary disease (COPD; 58%, 11 of 19), and dementia (60%, 15 of 25). Most prognostic criteria used clinicians' judgment (73%, 22 of 30). Most interventions included a nurse (70%, 69 of 98), and many were nurse-only (39%, 27 of 69). Social workers were well represented, and home-based approaches were common (56%, 70 of 124). Home interventions with visits were more effective than those without (64%, 28 of 44; vs. 46%, 12 of 26). Interventions improved communication and care planning (70%, 12 of 18), psychosocial health (36%, 12 of 33, for depressive symptoms; 41%, 9 of 22, for anxiety), and patient (40%, 8 of 20) and caregiver experiences (63%, 5 of 8). Many interventions reduced hospital use (65%, 11 of 17), but most other economic outcomes, including costs, were poorly characterized. Palliative care teams did not reliably lower healthcare costs (20%, 2 of 10). Conclusions: Palliative care improves cancer, CHF, COPD, and dementia outcomes. Effective models include nurses, social workers, and home-based components, and a focus on communication, psychosocial support, and the patient or caregiver experience. High-quality research on intervention costs and cost outcomes in palliative care is limited.

Journal of palliative medicine · systematic review · 135 citationsread the source →

Impulse control disorder behaviors associated with pramipexole used to treat fibromyalgia.

Objective: Compulsivity has been associated with use of dopamine agonists used to treat Parkinson's disease (PD). Increasing use of these agents to treat fibromyalgia (FM) raises concern for this unexpected toxicity in a new group of patients. This is the first report of compulsive gambling and shopping among patients taking dopamine agonists for treatment of FM. Design: A retrospective chart review of all patients in a large, active FM research practice was used to identify compulsivity associated with dopamine agonists and describe its remission following dug withdrawal. Results: Of 3006 patients with FM treated between 2002 and 2006, 1356 had taken > or =1 dose of a dopamine agonist ( >95% pramipexole). Twenty-one (3 male, 18 female) were identified with compulsive gambling (33%), shopping (40%) or both (27%) after taking a 4.5 mg mean dose of pramipexole at bedtime for 14.4 +/- 14.9 months. Compulsivity resolved in 3-10 days for 19 of 21 patients and by 3 months for all following a monitored, compulsory tapered discontinuation over 7 days. Conclusions: While biologic aspects of PD and FM differ considerably, compulsive gambling and shopping have become important, yet unexpected concerns related to use of dopamine agonists for patients with FM and their treating clinicians.

Journal of gambling studies · 51 citationsread the source →

Gynecologic cancer treatment and the impact of cancer-related infertility.

Objective: The objective of this study was to empirically assess the emotional and sexual impact of cancer-related infertility in women with a history of gynecologic cancer. Method: Women with a history of gynecologic cancer were approached during their gynecologic oncology clinic appointment; they were provided a description of the study and asked to participate. All participants completed a one-time self-report survey. We present data acquired via the following methods: Center for Epidemiologic Studies-Depression Scale (CES-D), Impact of Events Scale (IES), Modified Inventory of Traumatic Grief (M-ITG), Female Sexual Function Index (FSFI), and the Menopausal Symptom Checklist. Results: The study sample consisted of 20 women, ages 27 to 49 years (mean, approximately 40 years), who had undergone treatment for cervical (40%), ovarian (20%), or uterine (40%) cancer. Forty percent of the sample reported depressive symptoms as measured by the CES-D, with 35% of the women experiencing moderate to severe levels of distress as measured by the IES. The women in this sample experienced dissatisfaction with their overall sex lives (67%), pain during vaginal penetration (62%), and low levels of sexual desire (56%). Conclusions: The preliminary findings of this study indicated that feelings of depression, grief, stress, and sexual dysfunction are being experienced by women with a history of gynecologic cancer who have lost their fertility as a result of their cancer treatment.

Gynecologic oncology · 142 citationsread the source →

Effect of Family Navigation on Diagnostic Ascertainment Among Children at Risk for Autism: A Randomized Clinical Trial From DBPNet.

Importance: Early identification of autism spectrum disorder (ASD) is associated with improved cognitive and behavioral outcomes. Targeted strategies are needed to support equitable access to diagnostic services to ensure that children from low-income and racial/ethnic minority families receive the benefits of early ASD identification and treatment. Objective: To test the efficacy of family navigation (FN), an individually tailored, culturally informed care management strategy, to increase the likelihood of achieving diagnostic ascertainment among young children at risk for ASD. Design, setting, and participants: This randomized clinical trial of 249 families of children aged 15 to 27 months who had positive screening results for possible ASD was conducted in 11 urban primary care sites in 3 cities. Data collection occurred from February 24, 2015, through November 5, 2018. Statistical analysis was performed on an intent-to-treat basis from November 5, 2018, to July 27, 2020. Interventions: Families were randomized to FN or conventional care management (CCM). Families receiving FN were assigned a navigator who conducted community-based outreach to families to address structural barriers to care and support engagement in recommended services. Families receiving CCM were assigned to a care manager, who did limited telephone outreach. Families received FN or CCM after positive initial screening results and for 100 days after diagnostic ascertainment. Main outcomes and measures: The primary outcome, diagnostic ascertainment, was measured as the number of days from randomization to completion of the child's clinical developmental evaluation, when a diagnosis of ASD or other developmental disorder was determined. Results: Among 250 families randomized, 249 were included in the primary analysis (174 boys [69.9%]; mean [SD] age, 22.0 [3.5] months; 205 [82.3%] publicly insured; 233 [93.6%] non-White). Children who received FN had a greater likelihood of reaching diagnostic ascertainment over the course of 1 year (FN, 108 of 126 [85.7%]; CCM, 94 of 123 [76.4%]; unadjusted hazard ratio [HR], 1.39 [95% CI, 1.05-1.84]). Site (Boston, New Haven, and Philadelphia) and ethnicity (Hispanic vs non-Hispanic) moderated the effect of FN (treatment × site interaction; P = .03; Boston: HR, 2.07 [95% CI, 1.31-3.26]; New Haven: HR, 1.91 [95% CI, 0.94-3.89]; and Philadelphia: HR, 0.91 [95% CI, 0.60-1.37]) (treatment × ethnicity interaction; P < .001; Hispanic families: HR, 2.81 [95% CI, 2.23-3.54] vs non-Hispanic families: HR, 1.49 [95% CI, 1.45-1.53]). The magnitude of FN's effect was significantly greater among Hispanic families than among non-Hispanic families (diagnostic ascertainment among Hispanic families: FN, 90.9% [30 of 33], and CCM, 53.3% [16 of 30]; vs non-Hispanic families: FN, 89.7% [35 of 39], and CCM, 77.5% [31 of 40]). Conclusions and relevance: Family navigation improved the likelihood of diagnostic ascertainment among children from racial/ethnic minority, low-income families who were detected as at risk for ASD in primary care. Results suggest differential effects of FN by site and ethnicity. Trial registration: ClinicalTrials.gov Identifier: NCT02359084.

JAMA pediatrics · randomised controlled trial · 46 citationsread the source →

Depression and anxiety in long-term cancer survivors compared with spouses and healthy controls: a systematic review and meta-analysis.

Background: Cancer survival has improved in the past 20 years, affecting the long-term risk of mood disorders. We assessed whether depression and anxiety are more common in long-term survivors of cancer compared with their spouses and with healthy controls. Methods: We systematically searched Medline, PsycINFO, Embase, Science Direct, Ingenta Select, Ovid, and Wiley Interscience for reports about the prevalence of mood disorders in patients diagnosed with cancer at least 2 years previously. We also searched the records of the International Psycho-oncology Society and for reports that cited relevant references. Three investigators independently extracted primary data. We did a random-effects meta-analysis of the prevalences of depression and anxiety in cancer patients compared with spouses and healthy controls. Findings: Our search returned 144 results, 43 were included in the main analysis: for comparisons with healthy controls, 16 assessed depression and ten assessed anxiety; of the comparisons with spouses, 12 assessed depression and five assessed anxiety. The prevalence of depression was 11·6% (95% CI 7·7-16·2) in the pooled sample of 51 381 cancer survivors and 10·2% (8·0-12·6) in 217 630 healthy controls (pooled relative risk [RR] 1·11, 95% CI 0·96-1·27; p=0·17). The prevalence of anxiety was 17·9% (95% CI 12·8-23·6) in 48 964 cancer survivors and 13·9% (9·8-18·5) in 226 467 healthy controls (RR 1·27, 95% CI 1·08-1·50; p=0·0039). Neither the prevalence of depression (26·7% vs 26·3%; RR 1·01, 95% CI 0·86-1·20; p=0·88) nor the prevalence of anxiety (28·0% vs 40·1%; RR 0·71, 95% CI 0·44-1·14; p=0·16) differed significantly between cancer patients and their spouses. Interpretation: Our findings suggest that anxiety, rather than depression, is most likely to be a problem in long-term cancer survivors and spouses compared with healthy controls. Efforts should be made to improve recognition and treatment of anxiety in long-term cancer survivors and their spouses. Funding: None.

The Lancet. Oncology · meta-analysis · 536 citationsread the source →

Meditation or exercise for preventing acute respiratory infection: a randomized controlled trial.

Purpose: This study was designed to evaluate potential preventive effects of meditation or exercise on incidence, duration, and severity of acute respiratory infection (ARI) illness. Methods: Community-recruited adults aged 50 years and older were randomized to 1 of 3 study groups: 8-week training in mindfulness meditation, matched 8-week training in moderate-intensity sustained exercise, or observational control. The primary outcome was area-under-the-curve global illness severity during a single cold and influenza season, using the Wisconsin Upper Respiratory Symptom Survey (WURSS-24) to assess severity. Health care visits and days of missed work were counted. Nasal wash collected during ARI illness was assayed for neutrophils, interleukin-8, and viral nucleic acid. Results: Of 154 adults randomized into the study, 149 completed the trial (82% female, 94% white, mean age 59.3 ± 6.6 years). There were 27 ARI episodes and 257 days of ARI illness in the meditation group (n = 51), 26 episodes and 241 illness days in the exercise group (n = 47), and 40 episodes and 453 days in the control group (n = 51). Mean global severity was 144 for meditation, 248 for exercise, and 358 for control. Compared with control, global severity was significantly lower for meditation (P = .004). Both global severity and total days of illness (duration) trended toward being lower for the exercise group (P=.16 and P=.032, respectively), as did illness duration for the meditation group (P=.034). Adjusting for covariates using zero-inflated multivariate regression models gave similar results. There were 67 ARI-related days of-work missed in the control group, 32 in the exercise group (P = .041), and 16 in the meditation group (P <.001). Health care visits did not differ significantly. Viruses were identified in 54% of samples from meditation, 42% from exercise, and 54% from control groups. Neutrophil count and interleukin-8 levels were similar among intervention groups. Conclusions: Training in meditation or exercise may be effective in reducing ARI illness burden.

Annals of family medicine · randomised controlled trial · 91 citationsread the source →

Cognitive behaviour therapy-based intervention by community health workers for mothers with depression and their infants in rural Pakistan: a cluster-randomised controlled trial.

Background: The treatment of perinatal depression is a public-health priority because of its high prevalence and association with disability and poor infant development. We integrated a cognitive behaviour therapy-based intervention into the routine work of community-based primary health workers in rural Pakistan and assessed the effect of this intervention on maternal depression and infant outcomes. Methods: We randomly assigned 40 Union Council clusters in rural Rawalpindi, Pakistan, in equal numbers to intervention or control. Married women (aged 16-45 years) in their third trimester of pregnancy with perinatal depression were eligible to participate. In the intervention group, primary health workers were trained to deliver the psychological intervention, whereas in the control group untrained health workers made an equal number of visits to the depressed mothers. The primary outcomes were infant weight and height at 6 months and 12 months, and secondary outcome was maternal depression. The interviewers were unaware of what group the participants were assigned to. Analysis was by intention to treat. The study is registered as ISRCTN65316374. Findings: The number of clusters per group was 20, with 463 mothers in the intervention group and 440 in the control group. At 6 months, 97 (23%) of 418 and 211 (53%) of 400 mothers in the intervention and control groups, respectively, met the criteria for major depression (adjusted odds ratio (OR) 0.22, 95% CI 0.14 to 0.36, p<0.0001). These effects were sustained at 12 months (111/412 [27%] vs 226/386 [59%], adjusted OR 0.23, 95% CI 0.15 to 0.36, p<0.0001). The differences in weight-for-age and height-for-age Z scores for infants in the two groups were not significant at 6 months (-0.83 vs -0.86, p=0.7 and -2.03 vs -2.16, p=0.3, respectively) or 12 months (-0.64 vs -0.8, p=0.3 and -1.10 vs -1.36, p=0.07, respectively). Interpretation: This psychological intervention delivered by community-based primary health workers has the potential to be integrated into health systems in resource-poor settings.

Lancet (London, England) · randomised controlled trial · 616 citationsread the source →

The impact of trauma and daily hardships on the mental health of unaccompanied refugee minors detained in Libya.

Background: The high trauma load and prevalence of mental distress in unaccompanied refugee minors (URMs) who resettle in Western (European) countries is well documented. However, the lack of studies investigating the potentially most vulnerable population, URMs who are currently on the move in transit countries such as Libya, is alarming. Aims: To document the mental health of URMs detained in Libya and the possible associations with trauma, flight and daily hardships. Method: In total n = 99 (94.9% male; n = 93) URMs participated in this cross-sectional study conducted in four detention centres near the Libyan capital Tripoli. Data were collected via standardised questionnaires in an interview format and analysed using structured equation modelling. Results: Participants reported high rates of trauma, especially within Libya itself. Reports of daily hardships in detention ranged between 40 and 95% for basic needs and between 27 and 80% for social needs. Higher social needs were associated with increased anxiety symptoms (β = 0.59; P = 0.028) and increased pre-migration (β = 0.10; P = 0.061) and peri-migration trauma (β = 0.16; P = 0.017) with symptoms of depression. Similarly, higher levels of pre-migration trauma were associated with higher post-traumatic stress disorder levels (β = 0.17; P = 0.010). Conclusions: The rates of daily hardships and traumatic events are higher compared with those recorded for URMs living in asylum centres in Europe. The emotional, social and cognitive development of detained URMs is severely threatened in both the short and long term. This paper outlines some of the most detrimental effects of migration policies on URMs transiting through Libya.

BJPsych open · 10 citationsread the source →

Clinical outcomes on B/F/TAF and dolutegravir-based regimens at 12 months following regimen switch: an observational cohort study.

Background: This retrospective observational study evaluated the clinical use and treatment outcomes in virologically suppressed people with HIV (PWH) switching to either bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir (DTG)-based regimens (single- and multi-tablet formulations (STR and MTR)). Methods: We analyzed electronic medical and dispensing records from Trio Health HIV Research Network for treatment-experienced PWH ≥ 18 years suppressed (viral load [VL] < 200 copies/mL) at switch to B/F/TAF, DTG STR (DTG/3TC, DTG/RPV, DTG/3TC/ABC) or most common DTG MTRs with VL at 12 months (+/-3) since switch between April 2019 and December 2024. Univariate comparisons: chi-square or t-test; characteristics associated with virologic suppression at 12 months: multivariable logistic regression [LR], controlling for age, gender, race, baseline CD4 count, regimen, and adherence (proportion days covered [PDC] ≥ 80%). Results: Of 3141 PWH, 66% switched to B/F/TAF, 27% to DTG STR, and 7% to DTG MTRs. Baseline characteristics differed significantly between groups: B/F/TAF group had a higher proportion of males (81% vs. 67% DTG MTR) and Black individuals (40% vs. 31% DTG STR), while the DTG STR and MTR groups had higher proportions of PWH with cardiovascular disease (35% and 39% respectively vs. 32% on B/F/TAF) and eGFR < 60 mL/min/1.73 m² (18% and 22% respectively vs. 8% on B/F/TAF). At 12 months post switch, proportion of individuals with PDC ≥ 80% was higher in the DTG STR group (76%) compared to DTG MTR (67%) and B/F/TAF (69%) with similar virologic suppression across groups (98%, 98%, and 97% respectively). In multivariable LR, there was an association of White race, PDC ≥ 80%, and CD4 ≥ 200 cells/mm3 with greater probability of suppression at 12 months. Conclusions: Despite differences in baseline characteristics and regimen adherence between individuals switched to B/F/TAF, DTG STRs, and MTRs, both B/F/TAF and DTG-based regimens were associated with high rates of virologic suppression. This data strongly supports the inclusion of these simple and safe regimens as switch options in virologically suppressed PWH. Baseline differences in patient demographics and characteristics may have impacted the adherence on B/F/TAF compared to DTG STR, however virologic outcomes were preserved, demonstrating the forgiveness of B/F/TAF in populations potentially facing adherence challenges.

AIDS research and therapy · cohort or longitudinalread the source →

Visual outcome in infants born to drug-misusing mothers prescribed methadone in pregnancy.

Background: Flash visual evoked potentials (VEPs) were abnormal in a cohort of 100 neonates exposed to maintenance methadone in utero. This prospective cohort study now describes clinical visual and electrophysiological outcomes at 6 months. Methods: Visual assessment included modified Atkinson test battery; strabismus, nystagmus, reduced visual acuity, delayed visual maturation or refractive error (>3 dioptres) defined a fail. Pattern-onset VEPs were recorded to 120', 60' and 15' checks. Results: 81 drug-exposed and 26 comparison infants (79% and 52% of the original cohorts) were assessed at a median age of 27 weeks (range 26-30). 90% of drug-exposed infants had been additionally exposed to illicit drugs and 41% to excess alcohol in utero. 40% of the drug-exposed cohort failed clinical visual assessment: the relative risk of abnormal assessment was 5.1 (95% CI 1.3 to 20; p=0.02). Nystagmus was particularly common. VEP peak times were slower and amplitudes smaller in drug-exposed infants, of whom 70% had one or more abnormal VEP parameter. Abnormal visual outcome at 6 months was not associated with the pattern of additional drug exposure or a history of neonatal abstinence. Conclusions: Abnormal visual electrophysiology in infants born to drug-misusing mothers prescribed maintenance methadone persists to 6 months of age, and is associated with abnormal clinical visual assessment.

The British journal of ophthalmology · cohort or longitudinal · 53 citationsread the source →

Heterogeneity of phenotypes in severe asthmatics. The Belgian Severe Asthma Registry (BSAR).

Unlabelled: The Belgian severe asthma registry is a web-based registry encompassing demographic, clinical, functional and inflammatory data of severe asthmatics (SA), aiming at improving awareness, knowledge on its natural history and subphenotypes, and offering tools to optimize care of this asthma population. Methods: The cross-sectional analyses of this registry included 350 SA as defined by the ATS (2000) from 9 Belgian centres, with at least one year follow up. Results: Mean age was 55 ± 14 yrs. SA were more frequently female (57%) and atopic (70%). Late-onset asthma (≥40 yr) was observed in 31% of SA. Current smokers represented 12% while 31% were ex-smokers. In addition to high doses ICS + LABA, 65% of patients were receiving LTRA, 27% anti-IgE and 24% maintenance oral corticosteroids (8 mg (Interquartile range-IQR:4-8) methylprednisolone). Despite impaired airflow (median FEV1:67%; IQR: 52-81) only 65% had a post-bronchodilator FEV1/FVC ratio <70%. The median blood eosinophil count was 240/mm³. The median FENO was 26 ppb (IQR: 15-43) and 22% of SA had FENO ≥ 50 ppb. Induced sputum was successful in 86 patients. Eosinophilic asthma (sputum Eos ≥ 3%) was the predominant phenotype (55%) while neutrophilic (sputum Neu ≥ 76%) and paucigranulocytic asthma accounted for 22% and 17% respectively. Comorbidities included rhinitis and chronic rhinosinusitis (49%), nasal polyposis (19%), oesophageal reflux (36%), overweight and obesity (47%) and depression (19%). In addition, 8% had aspirin-induced asthma and 3% ABPA. Asthma was not well-controlled in 83% according to ACT < 20 and 77% with ACQ > 1.5. Conclusion: In this cohort of patients with severe asthma, the majority displayed indices of persistent airflow limitation and eosinophilic inflammation despite high-dose corticosteroids, suggesting potential for eosinophil-targeted biotherapies.

Respiratory medicine · cohort or longitudinal · 199 citationsread the source →

Cardiac iodine-123 metaiodobenzylguanidine imaging predicts sudden cardiac death independently of left ventricular ejection fraction in patients with chronic heart failure and left ventricular systolic dysfunction: results from a comparative study with signal-averaged electrocardiogram, heart rate variability, and QT dispersion.

Objectives: We prospectively compared the predictive value of cardiac iodine-123 metaiodobenzylguanidine (MIBG) imaging for sudden cardiac death (SCD) with that of the signal-averaged electrocardiogram (SAECG), heart rate variability (HRV), and QT dispersion in patients with chronic heart failure (CHF). Background: Cardiac MIBG imaging predicts prognosis of CHF patients. However, the long-term predictive value of MIBG imaging for SCD in this population remains to be elucidated. Methods: At entry, cardiac MIBG imaging, SAECG, 24-h Holter monitoring, and standard 12-lead electrocardiography (ECG) were performed in 106 consecutive stable CHF outpatients with a radionuclide left ventricular ejection fraction (LVEF) <40%. The cardiac MIBG washout rate (WR) was obtained from MIBG imaging. Furthermore, the time and frequency domain HRV parameters were calculated from 24-h Holter recordings, and QT dispersion was measured from the 12-lead ECG. Results: During a follow-up period of 65 +/- 31 months, 18 of 106 patients died suddenly. A multivariate Cox analysis revealed that WR and LVEF were significantly and independently associated with SCD, whereas the SAECG, HRV parameters, or QT dispersion were not. Patients with an abnormal WR (>27%) had a significantly higher risk of SCD (adjusted hazard ratio: 4.79, 95% confidence interval: 1.55 to 14.76). Even when confined to the patients with LVEF >35%, SCD was significantly more frequently observed in the patients with than without an abnormal WR (p = 0.02). Conclusions: Cardiac MIBG WR, but not SAECG, HRV, or QT dispersion, is a powerful predictor of SCD in patients with mild-to-moderate CHF, independently of LVEF.

Journal of the American College of Cardiology · cohort or longitudinal · 154 citationsread the source →

Measuring EQ-5D-5L utility values in parents who have experienced perinatal death.

Background: Policymakers use clinical and cost-effectiveness evidence to support decisions about health service commissioning. In England, the National Institute for Health and Care Excellence (NICE) recommend that in cost-effectiveness analyses "effectiveness" is measured as quality-adjusted life years (QALYs), derived from health utility values. The impact of perinatal death (stillbirth/neonatal death) on parents' health utility is currently unknown. This knowledge would improve the robustness of cost-effectiveness evidence for policymakers. Objective: This study aimed to estimate the impact of perinatal death on parents' health utility. Methods: An online survey conducted with mothers and fathers in England who experienced a perinatal death. Participants reported how long ago their baby died and whether they/their partner subsequently became pregnant again. They were asked to rate their health on the EQ-5D-5L instrument (generic health measure). EQ-5D-5L responses were used to calculate health utility values. These were compared with age-matched values for the general population to estimate a utility shortfall (i.e. health loss) associated with perinatal death. Results: There were 256 survey respondents with a median age of 40 years (IQR 26-40). Median time since death was 27 months (IQR 8-71). The mean utility value of the sample was 0.774 (95% CI 0.752-0.796). Utility values in the sample were 13% lower than general population values (p < 0.05). Over 10 years, this equated to a loss of 1.1 QALYs. This reduction in health utility was driven by anxiety and depression. Conclusions: Perinatal death has important and long-lasting health impacts on parents. Mental health support following perinatal bereavement is especially important.

The European journal of health economics : HEPAC : health economics in prevention and care · 6 citationsread the source →

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 →

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. Am J Physiol Regul Integr Comp Physiol 281: R591-R595, 2001.Link | ISI | Google Scholar3 Aoyagi N, Ohashi K, and Yamamoto Y. Frequency characteristics of long-term heart rate variability during constant-routine protocol. Am J Physiol Regul Integr Comp Physiol 285: R171-R176, 2003.Link | ISI | Google Scholar4 Arora RC, Hirsch GM, Johnson Hirsch K, Hancock Friesen C, and Armour JA. Function of human intrinsic cardiac neurons in situ. Am J Physiol Regul Integr Comp Physiol 280: R1736-R1740, 2001.Link | ISI | Google Scholar5 Barbieri R, Triedman JK, and Saul JP. Heart rate control and mechanical cardiopulmonary coupling to assess central volume: a systems analysis. Am J Physiol Regul Integr Comp Physiol 283: R1210-R1220, 2002.Link | ISI | Google Scholar6 Barrett CJ, Navakatikyan MA, and Malpas SC. Long-term control of renal blood flow: what is the role of the renal nerves? Am J Physiol Regul Integr Comp Physiol 280: R1534-R1545, 2001.Link | ISI | Google Scholar7 Blumberg MS, Knoot TG, and Kirby RF. Neural and hormonal control of arterial pressure during cold exposure in un-anesthetized week-old rats. Am J Physiol Regul Integr Comp Physiol 281: R1514-R1521, 2001.Link | ISI | Google Scholar8 Boyett MR, Kodama I, Honjo H, Arai A, Suzuki R, and Toyama J. Ionic basis of the chronotropic effect of acetylcholine on the rabbit sinoatrial node. Cardiovasc Res 29: 867-878, 1995.Crossref | PubMed | ISI | Google Scholar9 Braga and of on fluctuations and changes in blood pressure. Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google and elicited of heart rate variability. J Physiol | ISI | Google and modulation of sympathetic nerve activity to muscle in Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google and and GABA mediate suprachiasmatic nucleus inputs to spinal-projecting paraventricular Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and is not associated with of the exercise reflex in Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google C, and Y. The effect of on the circadian control of human core body temperature is Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and of adenosine receptors in the does not affect the in awake rats. Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google JK, A, and circadian and during two Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and sympathetic nerve and heart rate spectral effects of lower body negative pressure. Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google Francis Johnson and of heart failure after myocardial in the Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google A, and of lower body pressure on muscle sympathetic nerve activity response to Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and Adenosine initial depression of in the rat in Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google R, and and circadian phase in a diurnal the Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and Johnson alterations and autonomic in an model of Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google MA, and The interaction of the Bainbridge and in the conscious Res | ISI | Google A, and handgrip exercise arterial control of sympathetic in Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and nerve regulation to is in rats. Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and in heart rate variability. J Physiol | ISI | Google and function and cardiovascular interactions and Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and interval variability in isolated working rat hearts at various conditions and Res | PubMed | Google A, A, and and autonomic of in patients with mild Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google Malpas SC. Neural on cardiovascular and Am J Physiol Heart Physiol 2002.Link | ISI | Google and thermoregulation in and rats in a Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and effects on reflex responses to mental stress in Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and reflex during orthostatic in Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and and responses to and are in rats. Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and and in a by cycle. Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and of humoral heart rate regulation in the Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google Armour and within the intrinsic cardiac nervous system contribute to chronotropic regulation. Am J Physiol Regul Integr Comp Physiol 285: 2003.Link | ISI | Google Rentero N, A, and McAllen of cardiac vagal motoneurons in rat nucleus ambiguus. Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and modulate control of heart rate in conscious rats. Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google and central actions of angiotensin to increase arterial pressure. Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and modulate control of renal sympathetic nerve activity. Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and modulation of cardiovascular and autonomic function in role of Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and Inhibition of sympathetic responses at birth in by of the paraventricular Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and JP. pattern of during acute and chronic in conscious adult rats. Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google Armour and of chronic cardiac on of canine intracardiac neurons in Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and levels and circadian rhythm of activity in the a model of Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and nerve response of suprachiasmatic nucleus and Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google

American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · review · 309 citationsread the source →

Metastasis Suppressor Proteins: Discovery, Molecular Mechanisms, and Clinical Application

Clinically and experimentally, primary tumor formation and metastasis are distinct processes — locally growing tumors can progress without the development of metastases. This observation prompted the hypothesis that the molecular processes regulating tumorigenicity and metastasis are distinguishable and could be targeted therapeutically. During the process of transformation and subsequent progression to a malignant phenotype, both genetic and epigenetic alterations alter a cell's ability to perceive and respond to signals that regulate normal tissue homeostasis. A minority of tumorigenic cells accrue the full complement of alterations that enables them to disseminate from the primary tumor, survive insults from the immune system and biophysical forces, and respond to growth-promoting and/or inhibitory signals from the distant tissues and thrive there. Identification of genes and proteins that specifically inhibit the ability of cells to form metastases (e.g., metastasis suppressors) is providing new insights into the molecular mechanisms that regulate this complex process. This review will highlight: (a) the functional identification of metastasis suppressors, (b) the signaling cascades and cellular phenotypes which are controlled or modulated by metastasis suppressors, and (c) opportunities for translation and clinical trials that are based on mechanistic studies regarding metastasis suppressors. The identification of nm23, the first metastasis suppressor gene, provided functional evidence for the existence of genes that specifically regulate metastasis (1, 2). Subsequent to this initial discovery, researchers used in vivo studies to identify additional metastasis suppressors. These pioneering studies used an unbiased approach to identify such candidates by demonstrating that ectopic expression of the putative suppressor gene inhibited the development of spontaneous macroscopic metastases without significantly affecting primary tumor growth (3–5). Recently, this definition has been extended to include genes which specifically inhibit metastatic colonization (i.e., experimental metastasis formation using i.v. injection). The use of in vivo assays is required because in vitro assays are often of inadequate complexity to sufficiently model the entire process of metastasis. Furthermore, there are currently no in vitro models that allow the study of preferential growth within different target tissues. Table 1 lists the proteins which have bona fide metastasis suppressor activity in vivo (i.e., suppression of metastasis following ectopic expression into metastatic cell lines). It is interesting to note that metastasis suppressor activity for many of these genes would not have been predicted a priori based on their known cellular function(s). Furthermore, the unbiased, functional strategy identified novel genes for which no cellular function was known at the time of discovery. Metastasis suppressors can impart their suppressive activity at one or more of the steps in the metastatic cascade (6). For example, in vivo studies showed that metastatic cancer cells which express ectopic KISS1, JNKK1/MKK4, MKK6, MKK7, TXNIP, nm23-H1, or SSeCKS proteins could successfully disseminate and lodge at secondary sites, but are suppressed in their ability to colonize (i.e., form overt metastases) target tissues (7–12). After lodging at secondary sites, disseminated cells may die, persist as nondividing cells, or initiate growth (13). Such pivotal cellular decisions depend on both the expression of a specific gene profile as well as the activation status of key signaling pathways and the cumulative inputs of timing, amplitude, and duration of signaling responses. In short, cells expressing metastasis suppressors grow at primary sites, but fail to proliferate at secondary or metastatic sites, suggesting differential responses to site-specific external signals. Although the observation that a gene of interest functions as a metastasis suppressor is an excellent starting point, research is now focused on the biochemical and molecular mechanisms by which metastasis suppressor proteins execute their in vivo functions. Metastasis suppressors vary widely in their cellular locations and biochemical functions. Such proteins could display either extracellular (e.g., KISS1) or intracellular localization patterns. Within the cell, they are located in various cellular compartments, from the plasma membrane (e.g., cadherin, KAI1, CD44), cytoskeleton (e.g., RhoGDI2, gelsolin), cytosol (e.g., JNKK1/MKK4, nm23-H1, RKIP), mitochondria (e.g., caspase 8), and nucleus (e.g., BRMS1, CRSP3, TXNIP) (14–21).Cells respond to external stimuli by using a limited number of signaling pathways. Signaling specificity is achieved, at least in part, by combinatorial spatiotemporal activation of signaling proteins. The summation of these signaling events, enabled by a cell-specific gene expression profile, is a tailored, situation-appropriate response. During the process of transformation and progression to a malignant phenotype, both genetic and epigenetic alterations influence a cell's ability to perceive and respond to signals which regulate normal tissue homeostasis. The accumulation of such alterations during progressive rounds of cell division could endow a minority of tumorigenic cells with the ability to disseminate from the primary tumor. It is likely that as a result of these changes, metastatic cells are no longer bound by tissue-of-origin–derived signaling specificity and acquire the ability to modulate their responses to the changing environments encountered throughout the metastatic cascade. Current data supports a model in which ectopic expression of metastasis suppressor proteins may restore, at least in part, the endogenous signaling repertoire of earlier, more benign cellular generations, thereby blocking metastasis formation. In this light, metastasis formation can be viewed as the result of a cell's ability to respond to multiple growth milieus as opposed to being restricted to growth in the microenvironment of the tissue of origin. Defining pathways regulating metastatic growth requires the integration and interpretation of data obtained over experimental settings ranging from the molecular interactions of specific proteins, to communication between signaling networks within single cells, and ultimately cellular interactions among populations of cells that yield a particular disease state. This line of inquiry is a particular challenge in studies of metastasis regulation because of the complexity and diversity of downstream events that take place in metastasis formation. The majority of metastasis suppressors identified participate in highly conserved eukaryotic signal transduction pathways. Based on their known biochemical functions, we have divided the metastasis suppressors into four general signaling categories: cytoskeletal signaling, mitogenic pathways, stress-activated pathways, and survival pathways (Fig. 1). Although it may seem straightforward to place a metastatic suppressor into a linear signaling pathway, it is important to be mindful that these pathways are, in fact, dynamic networks that exist in series and parallel leading to crosstalk and interplay; phenomena known as emergent properties. The cytoskeleton is a dynamic structure that enables motility, deformability, and flexibility, while maintaining cellular architecture. For most nonhematopoietic cells, motility is an ancillary function; however, as a nonhematopoietic cell transitions from the benign to the invasive to the metastatic state, motility becomes an increasingly paramount ability. Without a dynamic actin cytoskeleton, a tumor cell would be incapable of intravasation or extravasation, and the cellular deformability is necessary to complete the metastatic cascade. Not surprisingly, several proteins involved in cellular motility have been implicated as metastasis suppressors. The Rho family of GTP-binding proteins, which include Rho, Rac, and Cdc42, are central players in the regulation of actin dynamics. The Rho-GTPase family consists of small 20 to 30 kDa monomeric GTP-binding proteins that bind GDP/GTP and hydrolyze GTP, leading to the activation of downstream effector molecules (22). In this signaling scheme, metastasis suppressors have been identified as upstream inhibitors of the Rho family (23), or downstream effectors (24). RhoGDIs inhibit Rho family members by impeding the dissociation of GDP from Rho proteins, thereby locking the Rho protein in its inactive state, preventing Rho proteins from interacting with effector targets, and/or sequestering Rho-GTPases in the cytosol (25). RHOGDI2 was shown to suppress experimental lung metastasis but not affect in vitro growth or in vivo tumorigenicity. The Src-suppressed C kinase substrate is a protein kinase C substrate with protein scaffolding properties that have been shown to be a negative regulator of Rho family members (26). Reexpression of Src-suppressed C kinase substrate suppressed secondary lung metastases in nude mice and increased cell-cell adhesion, yet had little effect on primary tumor growth (10). Furthermore, Src-suppressed C kinase substrate reexpression at physiologic levels suppresses podosome formation and correlates with the induction of normal actin cytoskeletal structures and cell morphology, but not with the inhibition of Src kinase activity in cells (26).The finding that RhoGDI displayed the ability to suppress metastasis suggested that the downstream molecules it inhibits may have metastasis-promoting activities. This hypothesis seems to hold true in that mice deficient in RhoC, a target of RhoGDI, displayed a marked decrease in metastasis potential (27). Furthermore, specific inhibition of a downstream effector of Rho, ROCK, decreased tumor cell invasiveness in vitro and reduced the dissemination of tumor cells implanted in the peritoneal cavity in vivo (28). RhoGDI2 has also been shown to regulate secreted growth factors such as endothelin 1 (ET-1), which contribute to metastasis and will be discussed below (29). This prometastasic activation of effectors downstream of the Rho family is not universal. Gelsolin is a downstream effector of Rac that regulates the length of actin via its filament severing and capping activities. Overexpression of gelsolin has been shown to inhibit metastasis in vivo (24). Counterintuitively, gelsolin is an indispensable protein of podosomes, which are thought to play an active role in tissue invasion and matrix remodeling through their regulation of matrix metalloprotease (MMP) activity (30, 31).Cell interactions with the extracellular matrix and with neighboring cells trigger numerous responses that have essential roles in the regulation of behavior and fate. Integrin-mediated cell adhesions provide bidirectional links between the microenvironment and the cytoskeleton. This crosstalk between a cell and its local environment occurs whether the cell is benign, malignant, or metastatic. In this light, the cytoskeleton serves as a conduit for the integration and processing of intracellular and extracellular information; however, changes in the cytoskeletal program during pathologic progression may alter how this information is integrated and processed. Two metastasis suppressors have been shown to have interactions with integrins. Connective tissue growth factor is a 38-kDa cysteine-rich heparin-binding protein which is a secreted growth factor that can bind to integrins on the cell surface (32). Ectopic expression of connective tissue growth factor inhibited metastatic colonization by lung cancer cells (33). In contrast, the KAI1 metastasis suppressor protein is a member of the tetraspanin family of proteins and has been shown to interact with a myriad of cell surface proteins including other tetraspans (i.e., CD9, CD81), integrins β1 and β2, MHCII growth factor receptors, and intracellular signaling proteins such as protein kinase C (34). It has been hypothesized that KAI1 modulates integrin and growth receptor signaling by accelerating the rate of internalization via a protein kinase C–dependent pathway, thereby modulating cell adhesion and cell migration (34). Furthermore, KAI1 has been shown to decrease the integrin- and ligand-induced activation of the receptor tyrosine kinase c-Met, and independently decreases integrin-induced Src activation. Both c-Met and Src are thought to be required for invasion (35). A final observation with respect to the involvement of integrins in metastasis suppressor activity concerns caspase-8 function. Loss of caspase-8 in neuroblastoma cells leads to increased survival and an increased incidence of metastasis. The induction of caspase-8-mediated apoptosis seems to be due to unligated integrins because decreased expression of unligated integrins enhanced cell survival (36–38).Claudin-4 is a component of tight junctions which form the most apical component of intercellular junctional complexes where they establish cell polarity and cellular functions such as permeability (39, 40). These intercellular junctions not only carry out adhesive functions but also contain crucial components of signaling pathways that regulate epithelial proliferation and differentiation. Complementary in vitro and in vivo studies identified claudin-4 as an inhibitor of invasion and metastasis in pancreatic cancer cells and a target of transforming growth factor-β and extracellular signal-regulated kinase (ERK) signaling (40, 41).RECK, a membrane glycoprotein that encodes a GPI-anchored glycoprotein harboring three protease inhibitor–like domains, has been shown to negatively regulate MMP-2, MMP-9, and MT1-MMPs in vitro, suggesting that it is an important regulator of extracellular matrix remodeling. Furthermore, RECK-null mouse embryos displayed markedly elevated MMP activity. Interestingly, RECK is down-regulated by Ras signaling, a commonly altered pathway in many malignant cells (42).The role of some putative metastasis suppressors is more complex. There are several of a protein as a metastasis suppressor in one model and a potential tumor suppressor in For example, is a glycoprotein that responses of the cell to their cellular Although it has been in the that of has been shown to suppress metastasis in the cancer system other have that may metastatic activity a of the invasion and of and has been suggested to be a is not the only protein to have an role in metastasis. are a of that cell-cell adhesion in various tissues in a function is controlled by its Both and seem to inhibit cell migration and the in vivo metastatic potential of cells other studies have suggested that may invasion It is important to note that cancer cells of tissue used in several of the The tissue specificity of metastasis suppressor function is with the and integration information through signal transduction is a secreted protein and is hypothesized to processing by The are known as or not be secreted in to its metastatic suppressor activity has yet to be at the identification of upstream of identified a metastasis suppressor activity for CRSP3, a of the receptor of cells with suppressed metastasis and was with an of providing a potential between these and metastasis regulation stress-activated protein and pathways in parallel to the protein kinase In to the of with and have been with cell and apoptosis in to and changes, and growth factor specifically either or The protein is a kinase that has been shown to and the and in to a of extracellular can function as a metastasis suppressor in both and cancer Complementary in vitro and in vivo assays showed that the kinase activity of is required for the suppression of overt metastases and is to Subsequent studies identified metastasis suppressor for and in and interest is the finding that in cancer signals through the of the pathway to suppress metastasis in cancer signals through the of the pathway to suppress metastasis In vivo studies that both and suppress the formation of overt metastases by the ability of disseminated cells to colonize the lung identification of a metastasis suppressor function for protein also or protein mechanistic between the to cellular and of metastatic ability. is an endogenous inhibitor of a component of a system that has been implicated in cancer progression The levels of in cells are by endogenous as the in to to and including The primary of cellular is the is through of membrane or in to to with molecular or thereby highly or a of events that result in cell and of metastasis. this and ectopic expression of modulates these events to suppress metastasis formation is currently pathway is by mitogenic such as growth growth or which receptor tyrosine and The of mitogenic factors to cell surface a series of that with the activation of various factors and proteins and regulation may at in this is through both the of a kinase for a as well as protein expression levels of regulation are by intracellular localization and with scaffolding or proteins. These events may be important for regulating metastatic In the of metastasis the protein with the by to and the kinase suppressor of Ras a protein that has a role in the regulation of Ras activity and activation of the pathway has been shown to regulate signaling, suggesting that metastasis suppression activity may be by the inhibition of signaling kinase inhibitor protein was identified as a metastasis suppressor gene in functions as a negative upstream regulator of signaling and kinase interact with at sites, and of either inhibits of the Both be in to inhibition may suppress metastasis by of metastasis suppressors, and are with the signaling The signaling pathway a key role in many of cell survival and 1 are of an inhibitory and a and signals from various cellular proteins such as and an integration for the activation of and downstream to a that a of downstream targets, the and also regulates a of target proteins that cell proliferation and survival The levels of are and several particular interest is the which to signaling metastasis suppressor protein has been with the of cells showed decreases in endogenous levels of (i.e., of This finding is with a model in which changes in signaling the ability of disseminated cells to survive in the and grow at secondary In contrast, expression of the metastasis suppressor is modulated by clinical is the finding that expression correlates significantly with in both and cancer and that the in as a significantly of and cancer survival either evidence from the cell molecular and genetic studies that the metastatic process requires many steps to The of only one in this of in vivo events the process and a This enabled the identification of metastasis suppressor proteins. the of the however, the is not as straightforward because which signaling in the metastatic process are is not have insights into this by metastatic colonization as the in the metastatic cascade that is from a of A clinical will this to of invasive are with metastatic and (i.e., These that many with invasive disease disseminated cancer cells at preventing the of disseminated cells into the metastatic (i.e., the process of would a for cancer This approach more at preventing cancer cells from the primary tumor for the that this process has place the is first with In where this process has not yet local such as and can the the for additional at the an for metastasis preventing the growth of disseminated tumor cells into an overt clinical metastasis or the metastases. the approach not the in hold disease in providing increased of the with both of these is the identification of at for disease that they may at metastatic that can be to this include both tumor as well as molecular of the primary tumor to the development of metastasis a it has been to of the disseminated tumor cells at a secondary as the and as being distinct from that at the primary with to the tumor tumor cells distinct in the primary and secondary sites, and these interactions can or include locally and as well as cell-cell interactions in environments such as the and these with the of metastasis suppressor protein one can to there are to metastasis suppressor proteins. The of these on of the leading to of metastasis suppressor protein For example, the gene is it that of a normal gene would be the In contrast, was secondary to suppressed for example, at the endogenous gene seem we will provide an of approach from that have the of the first identified metastasis a of metastasis suppressor protein function in disseminated tumor In many cancer is with metastasis that occurs A study used gene to and whether this would cancer metastasis in an model of this A cell line of metastatic potential to the by in vivo was used to the of reexpression on metastasis. of these cells, an expressing was This in expression of the gene in most of the tumor cells in in and was with a in the number of metastases and a of This of of the of induction as a approach The of this approach are also to the of which is a disease that the In with gene is and the with i.v. development from the also the of the metastasis gene but the approach reexpression of the endogenous gene as a the was to a that would expression and allow at to on at of the This of would a that is and with an and have been to For example, was to expression in a cell line elevated the expression of cells out an of the the that elevated the expression of metastatic cell is a used at in and as well as at in cancer Furthermore, elevated expression and inhibited colonization and this effect was through The effect of on the of expression was in an in vivo model system for the of metastases the cell line to lung mice to or in of mice to of The number of metastases mouse was reduced by to on the metastases in reduced by to in the inhibited the number and of metastases in this This in metastases was with reexpression in the lung a of in with metastases and and tumors is of gene expression alterations with of metastasis suppressor protein A would be that functional of metastasis suppressor proteins is with gene expression changes, and cellular Recently, this with the that of metastasis suppressor proteins is with the of was used to a novel These studies focused on RhoGDI2, a suppressor of metastasis in an model of cancer metastasis reduced expression was to be with decreased survival for with cancer that RhoGDI2 as a on the expression of genes and to identify such genes in a of the lung metastasis model and primary clinical of RhoGDI2 protein is currently they to proteins or pathways downstream of These genes required to be following the of RhoGDI2 protein from the cells, and be of being inhibited by or to the changes in gene expression following of RhoGDI2 expression in metastatic cells, several proteins including This finding was by the between RhoGDI2 expression levels and of in tumor (29). Furthermore, inhibition of the endothelin with of the endothelin receptor such as to metastatic suppression in cells deficient for RhoGDI2 (29). The endothelin has been shown to regulate tissue cell cell and remodeling also has on cells in the and lung important of cancer metastasis In to such may growth factor and factor and growth factor one in the proliferation of and cells tumor also a role for in metastases from and and supports a model in which cells, in providing a microenvironment for these that trials with endothelin may be for with cancer following of the primary The for its use in the from the effect these have had in preventing experimental metastasis. These however, not the of these in metastatic but this is yet to be The molecular shown between and RhoGDI2 is because of endothelin receptor A such as with clinical In fact, in with in a the most events and that is well In this there was no at to in other of was not by this the of this effector approach to other metastasis suppressor proteins could identify potential novel for in other for and during the of key of this

Clinical Cancer Research · review · 131 citationsread the source →

Roles for pituitary adenylate cyclase-activating peptide (PACAP) expression and signaling in the bed nucleus of the stria terminalis (BNST) in mediating the behavioral consequences of chronic stress.

Anxiety disorders are frequently long-lasting and debilitating for more than 40 million American adults. Although stressor exposure plays an important role in the etiology of some anxiety disorders, the mechanisms by which exposure to stressful stimuli alters central circuits that mediate anxiety-like emotional behavior are still unknown. Substantial evidence has implicated regions of the central extended amygdala, including the bed nucleus of the stria terminalis (BNST) and the central nucleus of the amygdala as critical structures mediating fear- and anxiety-like behavior in both humans and animals. These areas organize coordinated fear- and anxiety-like behavioral responses as well as peripheral stress responding to threats via direct and indirect projections to the paraventricular nucleus of the hypothalamus and brainstem regions (Walker et al. Eur J Pharmacol 463:199-216, 2003, Prog Neuropsychopharmacol Biol Psychiatry 33(8):1291-1308, 2009; Ulrich-Lai and Herman Nat Rev Neurosci 10:397-409, 2009). In particular, the BNST has been argued to mediate these central and peripheral responses when the perceived threat is of long duration (Waddell et al. Behav Neurosci 120:324-336, 2006) and/or when the anxiety-like response is sustained (Walker and Davis Brain Struct Funct 213:29-42, 2008); hence, the BNST may mediate pathological anxiety-like states that result from exposure to chronic stress. Indeed, chronic stress paradigms result in enhanced BNST neuroplasticity that has been associated with pathological anxiety-like states (Vyas et al. Brain Res 965:290-294, 2003; Pego et al. Eur J Neurosci 27:1503-1516, 2008). Here we review evidence that suggests that pituitary adenylate cyclase-activating polypeptide (PACAP) and corticotropin-releasing hormone (CRH) work together to modulate BNST function and increase anxiety-like behavior. Moreover, we have shown that BNST PACAP as well as its cognate PAC1 receptor is substantially upregulated following chronic stress, particularly in the BNST oval nucleus where PACAP-containing neurons closely interact with CRH-containing neurons (Kozicz et al. Brain Res 767:109-119, 1997; Hammack et al. Psychoneuroendocrinology 34:833-843, 2009). We describe how interactions between PACAP and CRH in the BNST may mediate stress-associated behaviors, including anorexia and anxiety-like behavior. These studies have the potential to define specific mechanisms underlying anxiety disorders, and may provide important therapeutic strategies for stress and anxiety management.

Journal of molecular neuroscience : MN · review · 100 citationsread the source →

Decisional Satisfaction, Regret, and Conflict Among Parents of Infants with Neurologic Conditions.

Objective: To characterize decisional satisfaction, regret, and conflict among parents of critically ill infants with neurologic conditions. Study design: In this prospective cohort study, we enrolled parents of infants with neurologic conditions in the intensive care unit (ICU). Hospital discharge surveys included the validated Family Satisfaction with the ICU (FS-ICU) decision making subscale, Decision Regret Scale (DRS), and Decisional Conflict Scale (DCS). We defined high satisfaction with decision making as an FS-ICU score ≥75, high decisional regret/conflict as DRS/DCS score >25, and within-couple disagreement as a difference of at least 25 points between scores. Results: We enrolled 61 parents of 40 infants (n = 40 mothers, n = 21 fathers); 35 mothers and 15 fathers completed surveys. Most mothers reported high satisfaction with decision making (27 of 35; 77%) and low decision regret (28 of 35; 80%); 40% (14 of 35) reported high decisional conflict. Mothers and fathers reported higher decisional conflict in the domains of uncertainty and values clarity compared with the domain of effective decision making (Bonferroni-corrected P < .05). There were no differences in decision outcomes between paired mothers and fathers; however, within any given couple, there were numerous instances of disagreement (7 of 15 for decision regret and 5 of 15 for decisional conflict). Conclusions: Many parents experience decisional conflict even if they ultimately have high satisfaction and low regret, underscoring the need for decision aids targeting uncertainty and values clarity. Couples frequently experience different levels of decisional regret and conflict.

The Journal of pediatrics · 14 citationsread the source →

Determining best methods to screen for religious/spiritual distress.

Purpose: This study sought to validate for the first time a brief screening measure for religious/spiritual (R/S) distress given the Commission on Cancer's mandated screening for psychosocial distress including spiritual distress. Methods: Data were collected in conjunction with an annual survey of adult hematopoietic cell transplantation (HCT) survivors. Six R/S distress screeners were compared to the Brief RCOPE, Negative Religious Coping subscale as the reference standard. We pre-specified validity as a sensitivity score of at least 85 %. As no individual measure attained this, two post hoc analyses were conducted: analysis of participants within 2 years of transplantation and of a simultaneous pairing of items. Data were analyzed from 1449 respondents whose time since HCT was 6 months to 40 years. Results: For the various single-item screening protocols, sensitivity ranged from 27 (spiritual/religious concerns) to 60 % (meaning/joy) in the full sample and 25 (spiritual/religious concerns) to 65 % (meaning/joy) in a subsample of those within 2 years of HCT. The paired items of low meaning/joy and self-described R/S struggle attained a net sensitivity of 82 % in the full sample and of 87 % in those within 2 years of HCT but with low net specificities. Conclusions: While no single-item screener was acceptable using our pre-specified sensitivity value of 85 %, the simultaneous use of meaning/joy and self-described struggle items among cancer survivors is currently the best choice to briefly screen for R/S distress. Future research should validate this and other approaches in active treatment cancer patients and survivors and determine the best times to screen.

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 46 citationsread the source →

Trends in Advance Care Planning in Patients With Cancer: Results From a National Longitudinal Survey.

Importance: Advance care planning (ACP) may prevent end-of-life (EOL) care that is nonbeneficial and discordant with patient wishes. Despite long-standing recognition of the merits of ACP in oncology, it is unclear whether participation in ACP by patients with cancer has increased over time. Objectives: To characterize trends in durable power of attorney (DPOA) assignment, living will creation, and participation in discussions of EOL care preferences and to explore associations between ACP subtypes and EOL treatment intensity as reflected in EOL care decisions and terminal hospitalizations. Design, setting, and participants: We analyzed prospectively collected survey data from 1985 next-of-kin surrogates of Health and Retirement Study (HRS) participants with cancer who died between 2000 and 2012, including data from in-depth "exit" interviews conducted with the surrogates after the participant's death. The HRS is a nationally representative, biennial, longitudinal panel study of US residents older than 50 years. Trends in ACP subtypes were tested, and multivariable logistic regression models examined for associations between ACP subtypes and measures of treatment intensity. Main outcomes and measures: Trends in the surrogate-reported frequency of DPOA assignment, living will creation, and participation in discussions of EOL care preferences; associations between ACP subtypes and both surrogate-reported EOL care decisions and terminal hospitalizations. Results: From 2000 to 2012, there was an increase in DPOA assignment (52% to 74%, P = .03), without significant change in use of living wills (49% to 40%, P = .63) or EOL discussions (68% to 60%, P = .62). Surrogate reports that patients received "all care possible" at EOL increased during the period (7% to 58%, P = .004), and rates of terminal hospitalizations were unchanged (29% to 27%, P = .70). Limiting or withholding treatment was associated with living wills (adjusted odds ratio [AOR], 2.51; 95% CI, 1.53-4.11; P < .001) and EOL discussions (AOR, 1.93; 95% CI, 1.53-3.14; P = .002) but not with DPOA assignment. Conclusions and relevance: Use of DPOA increased significantly between 2000 and 2012 but was not associated with EOL care decisions. Importantly, there was no growth in key ACP domains such as discussions of care preferences. Efforts that bolster communication of EOL care preferences and also incorporate surrogate decision makers are critically needed to ensure receipt of goal-concordant care.

JAMA oncology · editorial or comment · 100 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. Neurobiol. 23, 294–303. (doi:10.1016/j.conb.2013.01.017) Crossref, PubMed, ISI, Google Scholar3Levy DJ, Glimcher PW. 2012The root of all value: a neural common currency for choice. Curr. Opin. Neurobiol. 22, 1027–1038. (doi:10.1016/j.conb.2012.06.001) Crossref, PubMed, ISI, Google Scholar4Kringelbach ML, Berridge KC. 2009Towards a functional neuroanatomy of pleasure and happiness. Trends Cogn. Sci. 13, 479–487. (doi:10.1016/j.tics.2009.08.006) Crossref, PubMed, ISI, Google Scholar5Brown S, Gao X, Tisdelle L, Eickhoff LM. 2011Naturalizing aesthetics: brain areas for aesthetic appraisal across sensory modalities. Neuroimage 58, 250–258. (doi:10.1016/j.neuroimage.2011.06.012) Crossref, PubMed, ISI, Google Scholar6Reybrouck M, Eerola T. 2017Music and its inductive power: a psychobiological and evolutionary approach to musical emotions. Front. Psychol. 8, 494. (doi:10.3389/fpsyg.2017.00494) Crossref, PubMed, ISI, Google Scholar7Blood AJ, Zatorre RJ. 2001Intensely pleasurable responses to music correlate with activity in brain regions implicated in reward and emotion. Proc. Natl Acad. Sci. USA 98, 11 818–11 823. (doi:10.1073/pnas.191355898) Crossref, ISI, Google Scholar8Mallik A, Chandra ML, Levitin DJ. 2017Anhedonia to music and mu-opioids: evidence from the administration of naltrexone. Sci. Rep. 7, 41952. (doi:10.1038/srep41952) Crossref, PubMed, ISI, Google Scholar9Barrett LF. 2015How emotions are made: the secret life of the brain. London, UK: Macmillan. Google Scholar10Bloom P. 2010How pleasure works: the new science of why we like what we like. New York, NY: Norton. Google Scholar11Chatterjee A. 2014The aesthetic brain: how we evolved to desire beauty and enjoy art. New York, NY: Oxford University Press. Google Scholar12Spence C. 2017Gastrophysics: the new science of eating. London, UK: Penguin. Google Scholar13Leder H, Belke B, Oeberst A, Augustin D. 2004A model of aesthetic appreciation and aesthetic judgments. Br. J. Psychol. 95, 489–508. (doi:10.1348/0007126042369811) Crossref, PubMed, ISI, Google Scholar14Vessel EA, Rubin N. 2010Beauty and the beholder: highly individual taste for abstract, but not real-world images. J. Vis. 10, 1–14. (doi:10.1167/10.2.18) Crossref, PubMed, ISI, Google Scholar15Minissale G. 2013The psychology of contemporary art. Cambridge, UK: Cambridge University Press. Crossref, Google Scholar16Muth C, Pepperell R, Carbon C-C. 2013Give me Gestalt! Preference for cubist artworks revealing high detectability of objects. Leonardo 46, 488–489. (doi:10.1162/LEON_a_00649) Crossref, ISI, Google Scholar17Deacon TW. 1997The symbolic species: the co-evolution of language and the brain. New York, NY: Norton. Google Scholar18Henshilwood CS, d'Errico F. 2011Homo symbolicus: the dawn of language, imagination and spirituality. Amsterdam, The Netherlands: John Benjamins Publishing Co. Crossref, Google Scholar19Carroll N. 2008Aesthetic experience, art and artists. In Aesthetic experience (eds Shusterman R, Tomlin A), pp. 145–165. New York, NY: Routledge. Google Scholar20Kivy P. 2012What really happened in the eighteenth century: the 'Modern System' re-examined (again). Br. J. Aesthetics 52, 61–74. (doi:10.1093/aesthj/ayr046) Crossref, ISI, Google Scholar21Shiner L. 2001The invention of art: a cultural history. Chicago, IL: University of Chicago Press. Crossref, Google Scholar22Anderson RL. 1989Art in small-scale societies. 2nd edn. Englewood Cliffs, NJ: Prentice Hall. Google Scholar23Silvia PJ. 2009Looking past pleasure: anger, confusion, disgust, pride, surprise, and other unusual aesthetic emotions. Psychol. Aesthetics Creat. Arts 3, 48–51. (doi:10.1037/a0014632) Crossref, ISI, Google Scholar24Eco U. 2007On ugliness. London, UK: Harvill Secker. Google Scholar25Silvia PJ, Brown EM. 2007Anger, disgust, and the negative aesthetic emotions: expanding an appraisal model of aesthetic experience. Psychol. Aesthetics Creat. Arts 1, 100–106. (doi:10.1037/1931-3896.1.2.100) Crossref, Google Scholar26Huron D. 2006Sweet anticipation: music and the psychology of expectation. Cambridge, MA: MIT Press. Crossref, Google Scholar27Fitch W. 2006The biology and evolution of music: a comparative perspective. Cognition 100, 173–215. (doi:10.1016/j.cognition.2005.11.009) Crossref, PubMed, ISI, Google Scholar28Trainor LJ, Zatorre RJ. 2009The neurobiological basis of musical expectations. In The Oxford handbook of music psychology (eds Hallam S, Cross I, Thaut M), pp. 171–183. Oxford, UK: Oxford University Press. Google Scholar29Salimpoor VN, Benovoy M, Larcher K, Dagher A, Zatorre RJ. 2011Anatomically distinct dopamine release during anticipation and experience of peak emotion to music. Nat. Neurosci. 14, 257–262. (doi:10.1038/nn.2726) Crossref, PubMed, ISI, Google Scholar30Salimpoor VN, Zatorre RJ. 2013Neural interactions that give rise to musical pleasure. Psychol. Aesthetics Creat. Arts 7, 62–75. (doi:10.1037/a0031819) Crossref, ISI, Google Scholar31Whaley J, Sloboda J, Gabrielsson A. 2009Peak experiences in music. In The Oxford handbook of music psychology (eds Hallam S, Cross I, Thaut M), pp. 452–461. Oxford, UK: Oxford University Press. Google Scholar32Skov M, Nadal M.In press. Art is not special: an assault on the last lines of defense against the naturalization of the human mind. Rev. Neurosci. (doi:10.1515/revneuro-2017-0085) ISI, Google Scholar33Chatterjee A. 2011Neuroaesthetics: a coming of age story. J. Cogn. Neurosci. 23, 53–62. (doi:10.1162/jocn.2010.21457) Crossref, PubMed, ISI, Google Scholar34Pearce MT, Zaidel DW, Vartanian O, Skov M, Leder H, Chatterjee A, Nadal M. 2016Neuroaesthetics: the cognitive neuroscience of aesthetic experience. Perspect. Psychol. Sci. 11, 265–279. (doi:10.1177/1745691615621274) Crossref, PubMed, ISI, Google Scholar35Nadal M, Vartanian O, Skov M. 2017Psychological models of art reception must be empirically grounded. Behav. Brain Sci. 40, 36–37. (doi:10.1017/S0140525X17001790) Crossref, ISI, Google Scholar36Nadal M, Skov M. 2017Top–down and bottom–up: front to back: comment on 'Move me, astonish me… delight my eyes and brain: the Vienna integrated model of top–down and bottom–up processes in Art Perception (VIMAP) and corresponding affective, evaluative, and neurophysiological correlates' by Matthew Pelowski et al. Phys. Life Rev. 21, 148–149. (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 →

Prevalence and severity of symptoms across the menopause transition: cross-sectional findings from the Australian Women's Midlife Years (AMY) Study.

Background: The premenopause-to-perimenopause transition is defined by the Stages of Reproductive Aging Workshop +10 (STRAW+10) criteria according to changed menstrual cycle frequency. However, this approach is unhelpful for women and gender-diverse people with oligomenorrhoea or amenorrhoea, and also because a range of diverse symptoms have been ascribed to menopause. We investigated the prevalence and severity of symptoms from the late reproductive stage to late postmenopause, identifying those which might best differentiate menopause onset. Methods: The Australian Women's Midlife Years (AMY) Study was a nationally representative cross-sectional study of women aged 40-69 years who were recruited via a non-probability panel using online and offline sources between Oct 27, 2023, and March 19, 2024. To be eligible, participants needed to be able to complete a questionnaire in English. Menopausal symptoms were assessed using the Menopause-specific Quality of Life (MENQOL) questionnaire. Symptom prevalence and severity over the previous 4 weeks was calculated with 95% CIs, with prevalence ratios adjusted for age, BMI, and other demographic variables. Findings: 8096 women were recruited: 5509 women were classified using STRAW+10 as premenopausal (n=1250), early perimenopausal (n=344), late perimenopausal (n=271), and postmenopausal (n=3644). Among moderately-to-severely bothersome symptoms, hot flushes showed the greatest change in prevalence from premenopause (8·8% [95% CI 7·2-10·4]) to late perimenopause (37·3% [31·5-43·0]; adjusted prevalence ratio 4·74 [95% CI 3·64-6·19]). Less variation was apparent for other symptoms, including poor memory and low mood. Vaginal dryness was the most discriminative sexual symptom from premenopause to late perimenopause (adjusted prevalence ratio 2·54 [95% CI 1·78-3·61]). Women with vasomotor symptoms and changed menstrual flow had more prevalent moderately-to-severely bothersome symptoms compared with women without vasomotor symptoms. Compared with premenopausal women with vasomotor symptoms and changed menstrual flow, early perimenopausal women with vasomotor symptoms reported a higher prevalence of poor memory (adjusted prevalence ratio 1·36 [95% CI 1·06-1·75]). Interpretation: Our findings suggest that moderately-to-severely bothersome vasomotor symptoms can reliably indicate the onset of perimenopause in women with oligomenorrhoea or amenorrhoea. Although other symptoms might be caused or exacerbated by menopause, other factors contributing to their occurrence need to be considered and included in management and care. Additionally, treatment options and care pathways are crucial to improve wellbeing during the perimenopause. Funding: National Health and Medical Research Council. Translations: For the Chinese and Spanish translations of the abstract see Supplementary Materials section.

The lancet. Diabetes & endocrinology · 9 citationsread the source →

Control of a Nosocomial Outbreak of COVID-19 in a University Hospital.

Background: Nosocomial spread of coronavirus disease 2019 (COVID-19) causes clusters of infection among high-risk individuals. Controlling this spread is critical to reducing COVID-19 morbidity and mortality. We describe an outbreak of COVID-19 in Keio University Hospital, Japan, and its control and propose effective control measures. Methods: When an outbreak was suspected, immediate isolation and thorough polymerase chain reaction (PCR) testing of patients and health care workers (HCWs) using an in-house system, together with extensive contact tracing and social distancing measures, were conducted. Nosocomial infections (NIs) were defined as having an onset or positive test after the fifth day of admission for patients and having high-risk contacts in our hospital for HCWs. We performed descriptive analyses for this outbreak. Results: Between March 24 and April 24, 2020, 27 of 562 tested patients were confirmed positive, of whom 5 (18.5%) were suspected as NIs. For HCWs, 52 of 697 tested positive, and 40 (76.9%) were considered NIs. Among transmissions, 95.5% were suspected of having occurred during the asymptomatic period. Large-scale isolation and testing at the first sign of outbreak terminated NIs. The number of secondary cases directly generated by a single primary case found before March 31 was 1.74, compared with 0 after April 1. Only 4 of 28 primary cases generated definite secondary infection; these were all asymptomatic. Conclusions: Viral shedding from asymptomatic cases played a major role in NIs. PCR screening of asymptomatic individuals helped clarify the pattern of spread. Immediate large-scale isolation, contact tracing, and social distancing measures were essential to containing outbreaks.

Open forum infectious diseases · 43 citationsread the source →

Association of neighbourhood disadvantage and individual socioeconomic position with all-cause mortality: a longitudinal multicohort analysis.

Background: Few studies have examined the interactions between individual socioeconomic position and neighbourhood deprivation and the findings so far are heterogeneous. Using a large sample of diverse cohorts, we investigated the interaction effect of neighbourhood socioeconomic deprivation and individual socioeconomic position, assessed using education, on mortality. Methods: We did a longitudinal multicohort analysis that included six cohort studies participating in the European LIFEPATH consortium: the CoLaus (Lausanne, Switzerland), E3N (France), EPIC-Turin (Turin, Italy), EPIPorto (Porto, Portugal), Melbourne Collaborative Cohort Study (Melbourne, VIC, Australia), and Whitehall II (London, UK) cohorts. All participants with data on mortality, educational attainment, and neighbourhood deprivation were included in the present study. The data sources were the databases of each cohort study. Poisson regression was used to estimate the mortality rates and associations (relative risk, 95% CIs) with neighbourhood deprivation (Q1 being least deprived to Q5 being the most deprived). Baseline educational attainment was used as an indicator of individual socioeconomic position. Estimates were combined using pooled analysis and the relative excess risk due to the interaction was computed to identify additive interactions. Findings: The cohorts comprised a total population of 168 801 individuals. The recruitment dates were 2003-06 for CoLaus, 1989-91 for E3N, 1992-98 for EPIC-Turin, 1999-2003 for EPIPorto, 1990-94 for MCCS, and 1991-94 for Whitehall II. We use baseline data only and mortality data obtained using record linkage. Age-adjusted mortality rates were higher among participants residing in more deprived neighbourhoods than those in the least deprived neighbourhoods (Q1 least deprived neighbourhoods, 369·7 per 100 000 person-years [95% CI 356·4-383·2] vs Q5-most deprived neighbourhoods 445·7 per 100 000 person-years [430·2-461·7]), but the magnitude of the association varied according to educational attainment (relative excess risk due to interaction=0·18, 95% CI 0·08-0·28). The relative risk for Q5 versus Q1 was 1·31 (1·23-1·40) among individuals with primary education or less, but less pronounced among those with secondary education (1·12; 1·04-1·21) and tertiary education (1·16; 1·07-1·27). Associations remained after adjustment for individual-level factors, such as smoking, physical activity, and alcohol intake, among others. Interpretation: Our study suggests that the detrimental health effect of living in disadvantaged neighbourhoods is more pronounced among individuals with low education attainment, amplifying social inequalities in health. This finding is relevant to policies aimed at reducing health inequalities, suggesting that these issues should be addressed at both the individual level and the community level. Funding: The European Commission, European Regional Development Fund, the Portugese Foundation for Science and Technology.

The Lancet. Public health · 48 citationsread the source →

The wake maintenance zone shows task dependent changes in cognitive function following one night without sleep.

Study objectives: The interaction between homeostatic sleep pressure and circadian timing modulates the impact of sleep deprivation on cognition. We aimed to investigate how this interaction affects different cognitive functions. Methods: Twenty-three healthy volunteers (18 males; mean age = 25.4 ± 5.7 years) underwent 40 hours of sleep deprivation under constant routine conditions. Performance on the Psychomotor Vigilance Test and a cognitive battery assessing vigilant attention, complex attention, recognition memory, and working memory was assessed in the morning (27 hours awake) and evening (37 hours awake) during sleep deprivation and compared to well-rested performance 24 hours earlier. Circadian phase assessments confirmed evening tests occurred in the wake maintenance zone (WMZ). Results: Increased time awake significantly impacted performance on all measures except recognition memory. Post hoc analyses found performance on all measures was significantly impaired in the morning following 27 hours of sleep deprivation compared to well-rested performance 24 hours earlier. In contrast, complex attention and working memory were preserved in the WMZ after 37 hours awake compared to 24 hours earlier, while vigilant attention and PVT performance were significantly impaired. During sleep deprivation, composite scores of speed and accuracy were both impaired in the morning, while only speed was impaired during the WMZ. Conclusions: We observed task- and time-dependent effects of sleep deprivation, such that vigilant attention was significantly impaired after both 27 hours and 37 hours awake (compared to when well-rested at the same circadian clock time). In contrast, complex attention and working memory were impaired at 27 hours awake, but preserved in the WMZ despite increased homeostatic sleep pressure (37 hours awake).

Sleep · 26 citationsread the source →

Psychiatric Findings in Suspected and Confirmed Middle East Respiratory Syndrome Patients Quarantined in Hospital: A Retrospective Chart Analysis.

Objective: Little is known about the psychiatric complications or risk factors for depression in suspected or confirmed Middle East Respiratory Syndrome (MERS) patients quarantined in hospital. Methods: A retrospective chart review was performed of all the patients admitted to the acute MERS inpatient unit at the NMC during the 2015 outbreak. Results: 30 (75%) were confirmed to be MERS-CoV positive among 40 admitted cases. Among the 24 MERS survivors, 17 (70.8%) exhibited psychiatric symptoms and 10 (41.7%) received a psychiatric diagnosis and medication during their hospital stay. Suspected MERS patients did not exhibit psychiatric symptoms or receive a psychiatric diagnosis. 27 suspected or confirmed MERS patients (age 41.15±18.64, male 37.0%) completed psychological assessments. A multiple linear regression analysis revealed that the Korean National Health and Nutrition Examination Survey-Short form and the Impact of Event Scale-Revised scores were significantly positively correlated with Patient Health Questionnaire-9 scores. Conclusion: Our findings indicate that the acute treatment of MERS-CoV infections in quarantine had a significant impact on the patients' mental health. Furthermore, assessment of the risk factors for depression may identify vulnerable patients who require psychiatric care and attention during hospital quarantine.

Psychiatry investigation · 84 citationsread the source →

Potential treatment mechanisms in a mindfulness-based intervention for people with progressive multiple sclerosis.

Objectives: To explore putative mediators of a mindfulness-based intervention to decrease distress in people with multiple sclerosis (MS) and to explore the patients' perspectives on this intervention. Design: We used an explanatory mixed methods design incorporating quantitative data from a pilot randomized control trial and a qualitative interview study with people who completed the mindfulness intervention. Methods: People with MS (n = 40) completed standardized measures of distress (outcome), and acceptance, decentring, self-compassion, and self-efficacy (potential mediators). Semi-structured interviews (n = 15) of patients' experiences of the mindfulness intervention were analysed deductively and inductively. Results: Decentring post-intervention explained 13% of the 3-month change in distress and between 27% and 31% of concurrent changes in distress. Acceptance changed only slightly, and as a result, the indirect effect accounts for only 2% of future distress and between 3% and 11% of concurrent distress. Qualitative data showed that acceptance and self-compassion needed more time to develop, whereas decentring could be implemented readily after being introduced in the sessions. Self-efficacy also had a large mediating effect. Participants in their interviews talked about group dynamics and prior expectations as essential elements that determine their engagement with the course and their level of satisfaction. Conclusions: Mindfulness interventions for people with a chronic progressive condition may benefit from focusing on helping them to accept daily challenges and teach them to recognize their thoughts and feelings, allowing time for acceptance and self-compassion to develop. Group dynamics also play a fundamental role in the success of the mindfulness interventions. Statement of Contribution What is already known on this subject? Mindfulness courses improve psychological well-being for people with chronic conditions. Mindfulness courses have been successful in improving psychological well-being and symptom management for people with multiple sclerosis but we do not know how these courses work. What does this study add? Decentering and self-efficacy appear to be key mechanisms leading to reduced distress. Acceptance and self-compassion may need more time and practice to develop. Group dynamics and expectations of the mindfulness courses were also important elements of mindfulness.

British journal of health psychology · 29 citationsread the source →

Psychosexual health in gynecological cancer

The literature surrounding psychosexual health and cancer patients has primarily considered the functional aspects of the disease and its treatment at the major expense of the emotional sequelae. Sexual health is defined by WHO as: "a state of physical, emotional, mental, and social well-being in relation to sexuality; it is not merely the absence of disease, dysfunction or infirmity. Sexual health requires a positive and respectful approach to sexuality and sexual relationships, as well as the possibility of having pleasurable and safe sexual experiences, free of coercion, discrimination and violence" [1]. A principle goal of WHO is to assist its member states in achieving the highest attainable standard of health care for all, including sexual and reproductive health [2]. Global statistics show that the world's female population is carrying an overwhelming burden of need in this area. Over 200 million women cannot access modern contraception, and millions of women suffer rape, domestic violence, and sexual abuse, not only in the context of wars and criminal activities, but also in their own homes [2]. Although the physical sequelae of these disasters can be treated, such as treatment for sexually transmitted infections, the emotional impact can frequently be hidden, ignored, or may not reveal its impact until many years after the event. Any illness or traumatic life event, past or present, can lead to sexual problems in the lifetime of a woman, and gynecological cancer is no exception. It is the root cause or trigger for sexual difficulties in at least 50% of women affected [3]. In 2012, the estimated number of women living with gynecological cancers was over three million, which means that potentially 1.5 million gynecological cancer survivors could be affected by an associated sexual difficulty [4]. Within the context of gynecological cancer, many of these problems can be alleviated if recognized and acknowledged early in the cancer journey, therefore contributing dramatic improvements to a woman's overall well-being. It is now estimated that half of the population of either sex will develop cancer at some time in their life. Globally, 40% − 45% of women will have a sexual problem at some stage, with the prevalence increasing with age [5]. Between 10% and 90% of women with any cancer will have sexual problems [6] and over 50% of women with gynecological cancer will have either temporary or persistent sexual difficulties [3]. As diagnosis and treatments improve, the number of women surviving cancer will increase, and survivorship issues including quality of life have become increasingly important. Sexuality is a key component of most subjective measurable quality of life indicators [7]. Sexual function and enjoyment are important components of survivorship and should not be ignored. The most common sexual problems can be divided into two groups: problems of function and/or problems of desire. There is, however, a complex interplay of organic disorders with emotional and psychosocial issues, and these divisions are merely artificial. Formal definitions of female sexual dysfunction have been adopted, including the US classifications in the Diagnostic and Statistical Manual of Mental Disorders [8], although having a sexual difficulty does not constitute having a mental health disorder. Basson et al. [9] published a useful classification of the problems. Such classifications are useful for research purposes, but may often be less helpful when treating women. The predominant functional female sexual problem is pain on sexual intercourse, or dyspareunia. Deep dyspareunia describes intracoital pelvic pain, and superficial dyspareunia is pain on vaginal entry. Either could signify organic disease, and should be appropriately investigated. If no pathology is demonstrated, and the pain persists, then an emotional cause must be considered and pursued. Vaginismus, or involuntary spasm of the pubococcygeal and related musculature, can prevent sexual intercourse taking place. Good history taking can clarify whether there has been any penetration of the vagina, not only penile, but by fingers, sex toys, or tampons. If not, this is diagnostic of primary vaginismus, and apart from close inspection of the vulva and offer of gentle digital vaginal examination to determine the extent of the vaginismus, no further clinical investigation is warranted. Women with gynecological cancer are more likely to have secondary vaginismus caused by pain experienced from the disease or its treatment, and fear of the pain occurring during sex [10]. Loss of libido or loss of sexual interest on the other hand is a problem of desire. There are no physiological markers for loss of desire when its origins are psychogenic, with psychosocial contributions, past and present relationships, traumas, and emotional factors all inhibiting the woman's wish to be sexual. One of the key ways to determine the origins of the sexual difficulty is to ask about the sexual and emotional relationship between the woman and her partner before the cancer diagnosis. It should not be assumed that problems are all due to the cancer, as long-standing relationship problems may be disclosed, and need to be incorporated into any counselling. The exception to this is the woman who suddenly becomes menopausal following cancer treatment, who had no problems with sex or desire prior to her cancer therapy. Appropriate standard therapy for her menopausal symptoms should be considered; however, the impact of a cancer diagnosis will be life changing, and drug treatment of hormonal deprivation symptoms may not be sufficient without some psychological or counselling support, or may be contraindicated as in the case of breast and endometrial cancer [11]. A diagnosis of gynecological cancer is overwhelming. While the instinctive professional response from clinicians is to ensure long-term survival, sexual issues are important for quality of life and should be considered in the decision-making process [12]. Sexual dysfunction is one of the most common and distressing consequences of cancer treatment [13]. Many treatments are shown to have sexual impacts, both positive and negative, and should be discussed fully with the woman pre-treatment so that she can make an autonomous decision about her care. Early offer of discussion of sexual issues in the cancer journey can lead to better sexual outcomes. Cervical cancer is the most common gynecological cancer worldwide. Cervical cancer survivors are at risk of sexual pain disorders, no matter which modality of treatment is used. A small study of patients who underwent radical vaginal trachelectomy for early stage cervical cancer showed sexual dysfunction, including loss of libido, for up to one year following treatment; however, by 12 months, sexual activity had reached that of healthy women [14]. Following radical hysterectomy for locally advanced cervical cancer, there was no significant difference in sexual activity and enjoyment between women with benign or malignant disease; however, the cancer group had worse problems than healthy controls with body image and vaginal functioning [15]. In women with advanced cervical cancer given chemoradiotherapy, pain during intercourse was in fact reduced after treatment [16]. This may have been a result of the resolution of bleeding, discharge, and pelvic pain. However, the anxiety surrounding cancer remains for many women. Women surviving up to 15 years following cervical cancer treatment showed poorer quality of life than healthy controls, and those who had received radiotherapy were significantly more affected by sexual dysfunction than those who had surgery alone [17]. Despite this however, orgasm may be unimpaired following radiation [18]. Many additional needs were expressed by women with cervical cancer; however, sexuality and intimacy came to the fore as a predominant issue for survivorship [19]. It has been known for some time that the physical and emotional impact of ovarian cancer can be devastating, leading to sexual as well as global quality of life issues [20]. One study has shown a prevalence of 63% for sexual difficulties among women with a diagnosis of ovarian cancer [3]. The effects of chemotherapy and surgery, combined with the anxiety about survival can have a dramatic negative effect on the woman's libido, and even women who undertake risk-reducing salpingo-oophorectomy can suffer sexual dysfunction [21]. Many of these women are totally unprepared for the devastating effects of sudden menopause, with hot flushes, vaginal dryness, and loss of libido replacing a previously healthy sex life. This could be helped by more realistic counselling before the procedure, and increased postoperative emotional support. One study has shown that women who had surgery for endometrial cancer had no differences in their own sexual experience postoperatively, but compared with healthy controls, they had more sexual difficulties overall [22]. Women with Lynch syndrome who opt for preventive surgery tend to be happy overall with the surgery, but are often unprepared for the physical adverse effects of menopause [23]. In contrast, Moldovan et al. [24] has reported that, despite sometimes debilitating menopausal symptoms, there were no significant sexual difficulties associated with the procedure. Vulvectomy is a common treatment for vulvar malignancy. This is increasingly affecting younger women, who are HIV positive. Women with vulvar cancer can have many years of difficulties with sex due to often distressing vulvar symptoms and bleeding. Following treatment they still suffer severe dyspareunia and body image distortion due to the effects of treatment. Although a recent study showed no differences in psychosocial and sexual functioning before and after vulvectomy, it was acknowledged that women with vulvar malignancy have a high risk for sexual problems compared with healthy controls [25]. Factors associated with postoperative sexual difficulties are increased age, poor overall physical and mental health well-being, and extent of the surgical excision [25]. This often elderly group of patients is usually neglected from the psychosexual point of view. The majority of the literature related to sexuality and cancer stems from high-resource countries. Although most of these studies encompass all women, there is a lack of good published evidence on the treatment of the sexual sequelae of cancer in relation to ethnic minority groups, within a majority culture [26]. Furthermore, data from low- and middle-income countries are scant. Much of the literature focuses on sexual distress and activity in relation to HIV and AIDS which, of course, is a global priority; however, this focus on infection transmission should not take away from the emotional needs of the woman who suffers from gynecological cancer. Sexuality research around the globe must be perceived and researched in terms of cultural, spiritual, ethnic, and religious contexts. Sexual problems in women with gynecological cancer may be associated with adverse effects of surgical, hormonal, and chemical treatments, as well as by the cancer itself. Fortunately, emotional, sexual, and quality of life outcomes improve as less morbid, more minimally invasive surgical treatments for gynecological cancers develop [12]. Chemotherapy-induced ovarian failure in cancer patients is associated with all the possible symptoms of a sudden menopause, combined with the emotional impact not only of the cancer, but loss of physical well-being and fertility all at the same time. Vaginal dryness can be a major problem to those women who wish to have sex [27], and appropriate vaginal moisturizers and lubricants can help. The issue of vaginal estrogen is still debated, but should be discussed with the patient, weighing up the risk − benefit ratio for each individual. Vaginal estrogen will, in most cases, alleviate the dryness, but there may be concerns about using hormones, especially in relation to breast cancer where the evidence is unclear. The scientific data, however, support the safety of low dose vaginal estrogen therapy [28]. It is not well understood that following a few weeks of vaginal estrogen, the vagina thickens and cornifies and estrogen is not absorbed as a result. Newer treatments such as selective estrogen receptor modulators have been used in place of vaginal estrogen in women without cancer [29], and may prove good alternatives in the future [30]. There are non-hormonal vaginal moisturizers and lubricants to make sexual intercourse more comfortable. Unfortunately, some commercial sexual lubricants can be hyperosmolar and could cause epithelial disruption, facilitating HIV transmission [31]. Simple lubricants such as olive oil or liquid glycerin have been used successfully in interventions to alleviate pain on intercourse due to vaginal dryness, combining their use with physiotherapy and psychosexual counselling. Treatments with pelvic external beam radiotherapy and/or with brachytherapy may cause vaginal shortening, tightening, and lack of pliability. The use of vaginal dilators to overcome these complications is widespread, despite lack of conclusive evidence, either for or against, either with or without a coating of estrogen cream [32]. Unsurprisingly, the intrusion of inserting a plastic (or sometimes glass) tube into a tender vagina after treatment is a task that may carry a deep psychological and emotional impact [33], and will have resultant poor compliance. Radiation oncologists agree that information about dilator use should be given before treatment [34], and that sufficient patient information and support are essential to improve compliance. Sensitivity to emotions and women's views and personal values in relation to sexuality are essential supports to encouraging dilator use [35]. Any of the above problems cannot fail to have an emotional impact on the woman and on her partner. Many sexual difficulties are automatically blamed on the organic disruption caused by cancer and its treatments; however, once any clearly indicated treatments have been given, in a sizable proportion of cases, the sexual difficulty will remain unresolved. Many sexual difficulties are psychogenic, and no amount of skilled clinical treatments will help if not linked closely to appropriate counselling, psychological, or psychosexual therapy. This form of intervention will enable the woman to expose and reflect on her sexual difficulties, in the context of her life and relationship not only since the cancer, but beforehand. This is often a time when past problems, such as childhood abuse, or problems with her current partner will surface. Some partners are disgusted by the physical impacts of cancer, and the relationship will suffer. On the other hand, some partners become more supportive and the cancer leads to stronger relationships [36]. Classic psychosexual therapy, using brief, focused psychotherapeutic techniques is the mainstay of treatment. It can be used with an individual or a couple, of any sexual orientation or cultural or religious background. This is a way of listening reflectively to the patient, so that they can gain their own insights into their sexual problem. The issue of genital examination is considered if relevant, as it enables the woman to connect with her genital area, and may trigger deep-seated thoughts or anxieties that the woman had blocked emotionally. This, of course, is a technique used only by clinicians who are qualified to examine the patient [37]. Clinical psychologists and counsellors trained in psychosexual work also treat women with sexual problems. Globally, because the availability of trained personnel differs, many simple innovative treatment interventions have been tried. A brief intervention using a well-accepted treatment, cognitive behavioral therapy (CBT), combined with sexual health education had positive results on patients who had risk-reducing salpingo-oophorectomy [21]. Psychosexual interventions work [38], and like all psychodynamic interventions only require a trained counsellor and a means of allowing access to the patient. The internet has enabled access to health care for many people around the world who are not able to travel long and difficult land journeys to direct provision of health care. An online intervention with a professional moderator has proven acceptable to gynecological cancer patients with a sexual difficulty [39], and another internet-based sexual difficulties intervention with counselling sessions proved more successful in improving sexuality issues than without a counsellor; however, there was no difference between the two groups in relation to emotional distress and quality of life [40]. Elsewhere, telephone interventions are being used, also with some success; however, it is clear that the knowledge, skills, and training of the health professional providing the intervention are relevant to the patient outcome. Multidisciplinary care should form the backbone of treatment of sexual difficulties in women with gynecological cancer, incorporating physical, psychoeducational, and psychosexual input. Team discussions, including clinicians, psychosexual therapists, and physiotherapists are well within the capabilities of many cancer centers, remembering that the patient and her partner are the focal point and should always be consulted. It is impossible to diagnose and treat a sexual problem if one does not acknowledge that it exists. Many studies in the past have identified lack of willingness of doctors and nurses to discuss sex, but sadly recent research has shown that not much has changed. For instance, in a cohort sample of 1154 US obstetrician − gynecologists, 60% did not ask patients about sexual problems [41]. Too often clinicians make value judgements about their patients including whether sexuality is an important part of their lives. Such assumptions may include biases about age, appearance, sexual preferences, and marital status of people who have sex. People with cancer and their partners have unmet sexual information and support needs [42], often due to the unwillingness of healthcare professionals to discuss sexual issues, even though they recognize it may be important to the patient. There are many barriers to talking about sex, affecting both the patient and the clinician, such as cultural background, and age and gender discrepancies between doctor and patient. There may be simple barriers, such as lack of privacy in a consultation, as often cancer patients are accompanied by family or close friends. Patients often state that they feel it is trivial to take up the doctor's time with non-life-threatening issues such as sex. Clinicians often cite lack of training as a reason that they are uncomfortable talking about sex and poor provision of this training has been noted [13]. Different models of communication skills training have been used and those undertaking the training have shown greater empathy and were more inclined to use open questions [43]. This technique of speaking to the patient in an open rather than interrogative manner can easily facilitate discussion of intimate issues. An even greater challenge in communication is the recognition that individuals are sexual beings up to the end of life. To some women in the palliative phase, sexual touch and closeness to their partner is of vital importance. Sadly this is rarely recognized and addressed by palliative care physicians [44]. It is important to remember that a minority of the female population identifies as lesbian, and that about 8% of the population is bisexual. While this should make no difference to the quality of sexual health care they receive, lesbians and bisexuals find it difficult to disclose their sexuality to clinicians, often inhibited by their cultural or religious background, and fears of facing discrimination [45]. If the clinician asks the patient at the outset if they have a sexual partner, and whether the partner is male or female, it will greatly enhance the quality of the doctor − patient interaction. Lesbian partners in particular can be very supportive during the cancer journey, and should be given the opportunity to be present if the patient wishes. Despite the recognized need for treatment of sexual problems in menopause and gynecological cancer, there is poor provision of specialist training to ensure that this important area of service provision is met [46]. Undergraduate teaching is important, but it is only by recognizing psychosexual medicine in formal gynecology or oncology training, as a compulsory requirement of the course, that this situation will begin to be addressed. Innovative online programs [47] can make a major impact on global training opportunities and give trainees around the world an opportunity to gain some skills and insight into treating sexual difficulties in a nonjudgmental way. Owing to the global prevalence of sexual problems associated with gynecological cancer, it should be within every gynecologist's or oncologist's duty of care to the patient to be aware of and have some understanding of how to diagnose and facilitate treatment for sexual problems in a nonjudgmental manner. This is true holistic medicine, recognizing not only the cancer, but the woman behind the symptoms, and requires awareness of the emotional, social, and relationship aspects of the patient's life. The ability of any person to enjoy a sexual life free of coercion, shame, disease, or pain in a consensual manner is a fundamental element of the human rights of women, and should be an unequivocally accepted as part of her gynecological cancer care. To make a difference, even in the absence of expensive and sophisticated cancer treatments, just acknowledging, listening, and offering support to the woman with sexual difficulties related to cancer will ultimately have a major benefit to her quality of life. The author has no conflict of interest. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

International Journal of Gynecology & Obstetrics · 17 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 →

Parent Engagement With a Telehealth-Based Parent-Mediated Intervention Program for Children With Autism Spectrum Disorders: Predictors of Program Use and Parent Outcomes.

Background: There has been growing interest in using telehealth to increase access to parent-mediated interventions for children with ASD. However, little is known about how parents engage with such programs. Objective: This paper presents program engagement data from a pilot study comparing self-directed and therapist-assisted versions of a novel telehealth-based parent-mediated intervention for young children with autism spectrum disorders (ASD). Methods: Parents of young children with ASD were randomly assigned to receive a self-directed or therapist-assisted version of ImPACT Online. Parent engagement and satisfaction with the different components of the program website were examined using the program's automated data collection and a post-treatment evaluation survey. We examined the relationship between program engagement and changes in parent knowledge and implementation and participant characteristics associated with program engagement. Results: Of the 27 parent participants, the majority were female (26/27, 96%), married (22/27, 81%), with a college degree or higher (18/27, 66%), and less than half were employed outside of the home (10/27, 37%). The mean chronological age of the child participants was 43.26 months, and the majority were male (19/27, 70%) and white (21/27, 78%). Most of the families (19/27, 70%) resided in a rural or medically underserved area. Parents logged into the website an average of 46.85 times, spent an average of 964.70 minutes on the site, and completed an average of 90.17% of the lesson learning activities. Participants in the therapist-assisted group were more likely to engage with the website than those in the self-directed group: F2,24=17.65, P<.001. In total, 85% of participants completed the program, with a significantly greater completion rate in the therapist-assisted group (N=27): χ(2) 1=5.06, P=.03. Lesson learning activities were visited significantly more often than the supplemental activities (all Ps<.05). Multiple regression controlling for pretreatment performance indicated that program completion (beta=.51, P=.02) predicted post-treatment intervention knowledge, and program completion (beta=.43, P=.03) and group assignment (beta=-.37, P=.045) predicted post-treatment intervention fidelity. Partial correlations indicated that parent depressive symptoms at pretreatment were negatively associated with program completion (r=-.40, P=.04), but other key parent and child demographic factors were not. Post-treatment measures of website usability (r=.65, P<.001), treatment acceptability (r=.58, P=.002), and overall satisfaction (r=.58, P=.002) were all related to program completion. Conclusions: Parent engagement and satisfaction with ImPACT Online was high for both self-directed and therapist-assisted versions of the program, although therapist assistance increased engagement. Program completion was associated with parent outcomes, providing support for the role of the website in parent learning. This program has the potential to increase access to parent-mediated intervention for families of children with ASD.

Journal of medical Internet research · 88 citationsread the source →

Sexual victimisation, peer victimisation, and mental health outcomes among adolescents in Burkina Faso: a prospective cohort study.

Background: Sexual victimisation and peer victimisation are pervasive and increase risk for mental illness. Longitudinal studies that compare their unique and cumulative effects are scarce and have been done predominantly in high-income countries. The aims of this study were to examine the prevalence, prospective associations, and gender differences in sexual and peer victimisation and mental health in a low-income, African setting. Methods: In this prospective cohort study, data were obtained from the 2017 ARISE Adolescent Health Study, a population-representative, two-wave, prospective study of adolescents (aged 12-20 years) from Burkina Faso. A random sample of adolescents was drawn from ten villages, selected to capture the five main ethnic groups, and from one of the seven sectors of Nouna town, Burkina Faso, at two timepoints: Nov 12 to Dec 27, 2017, and Nov 15 to Dec 20, 2018. Standardised interviews were conducted in French or a local language by trained researchers. We measured victimisation exposure as sexual victimisation, peer victimisation, and polyvictimisation, using lifetime frequency of exposure, and we measured mental health symptoms and disorders using the Kutcher Adolescent Depression Scale, the Primary Care Post-Traumatic Stress Disorder screen IV and 5, and a question on lifetime self-harm and number of incidents in the past year. We calculated prevalence of victimisation and mental health symptoms and disorders at the two timepoints, and we used lifetime victimisation at the first timepoint to predict mental health at the second timepoint using logistic and negative binomial regressions. Gender differences were examined using interaction terms. Findings: Of 2544 eligible adolescents, 1644 participated at time 1 and 1291 participated at time 2. The final sample with data at both timepoints included 1160 adolescents aged 12-20 years (mean 15·1, SE 0·2), of whom 469 (40·4%) were girls and 691 (59·6%) were boys. The majority ethnic group was Dafin (626 [39·1%]), followed by Bwaba (327 [20·5%]), Mossi (289 [16·0%]), Samo (206 [13·0%]), Peulh (166 [9·7%]), and other (30 [1·6%]). After survey weight adjustment, sexual victimisation (weighted percentages, time 1, 256 [13·8%] of 1620; time 2, 93 [7·2%] of 1264) and peer victimisation (weighted percentages, time 1, 453 [29·9%] of 1620; time 2, 272 [21·9%] of 1264) were common, whereas polyvictimisation was more rare (weighted percentages, time 1, 116 [6·6%] of 1620; time 2, 76 [5·7%] of 1264). Longitudinally, sexual victimisation was associated with probable clinical disorder (adjusted odds ratio 2·59, 95% CI 1·15-5·84), depressive symptoms (adjusted incidence rate ratio [aIRR] 1·39, 95% CI 1·12-1·72), and symptoms of post-traumatic stress disorder (aIRR 2·34, 1·31-4·16). Peer victimisation was associated with symptoms of post-traumatic stress disorder (aIRR 1·89, 1·13-3·17) and polyvictimisation was associated with depressive symptoms (aIRR 1·34, 1·01-1·77). Girls reported more sexual victimisation (weighted percentages, 130 [17·3%] of 681 vs 126 [11·4%] of 939), boys reported more peer victimisation (weighted percentages, 290 [33·1%] of 939 vs 163 [25·2%] of 681), and there was a significant interaction between lifetime victimisation and gender for probable clinical disorder (F [degrees of freedom 7, sample 376] 2·16; p=0·030). Interpretation: Sexual and peer victimisation were common in the study setting and increased risk for mental health problems. Adolescent girls who have been sexually victimised are especially at risk of mental health problems. Interventions targeting sexual and peer violence in low-income settings are needed. Funding: Alexander von Humboldt Foundation, the Wellcome Trust, Fondation Botnar, and Harvard TH Chan School of Public Health.

The lancet. Psychiatry · 9 citationsread the source →

The Internet Gaming Disorder Scale.

Recently, the American Psychiatric Association included Internet gaming disorder (IGD) in the appendix of the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The main aim of the current study was to test the reliability and validity of 4 survey instruments to measure IGD on the basis of the 9 criteria from the DSM-5: a long (27-item) and short (9-item) polytomous scale and a long (27-item) and short (9-item) dichotomous scale. The psychometric properties of these scales were tested among a representative sample of 2,444 Dutch adolescents and adults, ages 13-40 years. Confirmatory factor analyses demonstrated that the structural validity (i.e., the dimensional structure) of all scales was satisfactory. Both types of assessment (polytomous and dichotomous) were also reliable (i.e., internally consistent) and showed good criterion-related validity, as indicated by positive correlations with time spent playing games, loneliness, and aggression and negative correlations with self-esteem, prosocial behavior, and life satisfaction. The dichotomous 9-item IGD scale showed solid psychometric properties and was the most practical scale for diagnostic purposes. Latent class analysis of this dichotomous scale indicated that 3 groups could be discerned: normal gamers, risky gamers, and disordered gamers. On the basis of the number of people in this last group, the prevalence of IGD among 13- through 40-year-olds in the Netherlands is approximately 4%. If the DSM-5 threshold for diagnosis (experiencing 5 or more criteria) is applied, the prevalence of disordered gamers is more than 5%.

Psychological assessment · 320 citationsread the source →

Effect of a Professional Coaching Intervention on the Well-being and Distress of Physicians: A Pilot Randomized Clinical Trial.

Importance: Burnout symptoms among physicians are common and have potentially serious ramifications for physicians and their patients. Randomized studies testing interventions to address burnout have been uncommon. Objective: To explore the effect of individualized coaching on the well-being of physicians. Design, setting, and participants: A pilot randomized clinical trial involving 88 practicing physicians in the departments of medicine, family medicine, and pediatrics who volunteered for coaching was conducted between October 9, 2017, and March 27, 2018, at Mayo Clinic sites in Arizona, Florida, Minnesota, and Wisconsin. Statistical analysis was conducted from August 24, 2018, to March 25, 2019. Interventions: A total of 6 coaching sessions facilitated by a professional coach. Main outcomes and measures: Burnout, quality of life, resilience, job satisfaction, engagement, and meaning at work using established metrics. Analysis was performed on an intent-to-treat basis. Results: Among the 88 physicians in the study (48 women and 40 men), after 6 months of professional coaching, emotional exhaustion decreased by a mean (SD) of 5.2 (8.7) points in the intervention group compared with an increase of 1.5 (7.7) points in the control group by the end of the study (P < .001). Absolute rates of high emotional exhaustion at 5 months decreased by 19.5% in the intervention group and increased by 9.8% in the control group (-29.3% [95% CI, -34.0% to -24.6%]) (P < .001). Absolute rates of overall burnout at 5 months also decreased by 17.1% in the intervention group and increased by 4.9% in the control group (-22.0% [95% CI, -25.2% to -18.7%]) (P < .001). Quality of life improved by a mean (SD) of 1.2 (2.5) points in the intervention group compared with 0.1 (1.7) points in the control group (1.1 points [95% CI, 0.04-2.1 points]) (P = .005), and resilience scores improved by a mean (SD) of 1.3 (5.2) points in the intervention group compared with 0.6 (4.0) points in the control group (0.7 points [95% CI, 0.0-3.0 points]) (P = .04). No statistically significant differences in depersonalization, job satisfaction, engagement, or meaning in work were observed. Conclusions and relevance: Professional coaching may be an effective way to reduce emotional exhaustion and overall burnout as well as improve quality of life and resilience for some physicians. Trial registration: ClinicalTrials.gov identifier: NCT03207581.

JAMA internal medicine · 218 citationsread the source →

Social Isolation and Loneliness Among San Francisco Bay Area Older Adults During the COVID-19 Shelter-in-Place Orders.

Background/objectives: Physical distancing during the COVID-19 pandemic may have unintended, detrimental effects on social isolation and loneliness among older adults. Our objectives were to investigate (1) experiences of social isolation and loneliness during shelter-in-place orders, and (2) unmet health needs related to changes in social interactions. Design: Mixed-methods longitudinal phone-based survey administered every 2 weeks. Setting: Two community sites and an academic geriatrics outpatient clinical practice. Participants: A total of 151 community-dwelling older adults. Measurements: We measured social isolation using a six-item modified Duke Social Support Index, social interaction subscale, that included assessments of video-based and Internet-based socializing. Measures of loneliness included self-reported worsened loneliness due to the COVID-19 pandemic and loneliness severity based on the three-item University of California, Los Angeles (UCLA) Loneliness Scale. Participants were invited to share open-ended comments about their social experiences. Results: Participants were on average aged 75 years (standard deviation = 10), 50% had hearing or vision impairment, 64% lived alone, and 26% had difficulty bathing. Participants reported social isolation in 40% of interviews, 76% reported minimal video-based socializing, and 42% minimal Internet-based socializing. Socially isolated participants reported difficulty finding help with functional needs including bathing (20% vs 55%; P = .04). More than half (54%) of the participants reported worsened loneliness due to COVID-19 that was associated with worsened depression (62% vs 9%; P < .001) and anxiety (57% vs 9%; P < .001). Rates of loneliness improved on average by time since shelter-in-place orders (4-6 weeks: 46% vs 13-15 weeks: 27%; P = .009), however, loneliness persisted or worsened for a subgroup of participants. Open-ended responses revealed challenges faced by the subgroup experiencing persistent loneliness including poor emotional coping and discomfort with new technologies. Conclusion: Many older adults are adjusting to COVID-19 restrictions since the start of shelter-in-place orders. Additional steps are critically needed to address the psychological suffering and unmet medical needs of those with persistent loneliness or barriers to technology-based social interaction.

Journal of the American Geriatrics Society · 234 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 →

Burden of Stroke in Europe: Thirty-Year Projections of Incidence, Prevalence, Deaths, and Disability-Adjusted Life Years.

Background and purpose: Prediction of stroke impact provides essential information for healthcare planning and priority setting. We aim to estimate 30-year projections of stroke epidemiology in the European Union using multiple modeling approaches. Methods: Data on stroke incidence, prevalence, deaths, and disability-adjusted life years in the European Union between 1990 and 2017 were obtained from the global burden of disease study. Their trends over time were modeled using 3 modeling strategies: linear, Poisson, and exponential regressions-adjusted for the gross domestic product per capita, which reflects the impact of economic development on health status. We used the Akaike information criterion for model selection. The 30-year projections up to 2047 were estimated using the best fitting models, with inputs on population projections from the United Nations and gross domestic product per capita prospects from the World Bank. The technique was applied separately by age-sex-country groups for each stroke measure. Results: In 2017, there were 1.12 million incident strokes in the European Union, 9.53 million stroke survivors, 0.46 million deaths, and 7.06 million disability-adjusted life years lost because of stroke. By 2047, we estimated an additional 40 000 incident strokes (+3%) and 2.58 million prevalent cases (+27%). Conversely, 80 000 fewer deaths (-17%) and 2.31 million fewer disability-adjusted life years lost (-33%) are projected. The largest increase in the age-adjusted incidence and prevalence rates are expected in Lithuania (average annual percentage change, 0.48% and 0.7% respectively), and the greatest reductions in Portugal (-1.57% and -1.3%). Average annual percentage change in mortality rates will range from -2.86% (Estonia) to -0.08% (Lithuania), and disability-adjusted life years' from -2.77% (Estonia) to -0.23% (Romania). Conclusions: The number of people living with stroke is estimated to increase by 27% between 2017 and 2047 in the European Union, mainly because of population ageing and improved survival rates. Variations are expected to persist between countries showing opportunities for improvements in prevention and case management particularly in Eastern Europe.

Stroke · 569 citationsread the source →

The Horyzons project: a randomized controlled trial of a novel online social therapy to maintain treatment effects from specialist first-episode psychosis services.

This study aimed to determine whether, following two years of specialized support for first-episode psychosis, the addition of a new digital intervention (Horyzons) to treatment as usual (TAU) for 18 months was more effective than 18 months of TAU alone. We conducted a single-blind randomized controlled trial. Participants were people with first-episode psychosis (N=170), aged 16-27 years, in clinical remission and nearing discharge from a specialized service. They were randomly assigned (1:1) to receive Horyzons plus TAU (N=86) or TAU alone (N=84) between October 2013 and January 2017. Horyzons is a novel, comprehensive digital platform merging: peer-to-peer social networking; theory-driven and evidence-informed therapeutic interventions targeting social functioning, vocational recovery and relapse prevention; expert clinician and vocational support; and peer support and moderation. TAU involved transfer to primary or tertiary community mental health services. The primary outcome was social functioning at 18 months as measured by the Personal and Social Performance Scale (PSP). Forty-seven participants (55.5%) in the Horyzons plus TAU group logged on for at least 6 months, and 40 (47.0%) for at least 9 months. Social functioning remained high and stable in both groups from baseline to 18-month follow-up, with no evidence of significant between-group differences (PSP mean difference: -0.29, 95% CI: -4.20 to 3.63, p=0.77). Participants in the Horyzons group had a 5.5 times greater increase in their odds to find employment or enroll in education compared with those in TAU (odds ratio, OR=5.55, 95% CI: 1.09-28.23, p=0.04), with evidence of a dose-response effect. Moreover, participants in TAU were twice as likely to visit emergency services compared to those in the Horyzons group (39% vs. 19%; OR=0.31, 95% CI: 0.11-0.86, p=0.03, number needed to treat, NNT=5). There was a non-significant trend for lower hospitalizations due to psychosis in the Horyzons group vs. TAU (13% vs. 27%; OR=0.36, 95% CI: 0.11-1.08, p=0.07, NNT=7). So, although we did not find a significant effect of Horyzons on social functioning compared with TAU, the intervention was effective in improving vocational or educational attainment, a core component of social recovery, and in reducing usage of hospital emergency services, a key aim of specialized first-episode psychosis services. Horyzons holds significant promise as an engaging and sustainable intervention to provide effective vocational and relapse prevention support for young people with first-episode psychosis beyond specialist services.

World psychiatry : official journal of the World Psychiatric Association (WPA) · 94 citationsread the source →

Predicting mid-life capital formation with pre-school delay of gratification and life-course measures of self-regulation.

How well do pre-school delay of gratification and life-course measures of self-regulation predict mid-life capital formation? We surveyed 113 participants of the 1967-1973 Bing pre-school studies on delay of gratification when they were in their late 40's. They reported 11 mid-life capital formation outcomes, including net worth, permanent income, absence of high-interest debt, forward-looking behaviors, and educational attainment. To address multiple hypothesis testing and our small sample, we pre-registered an analysis plan of well-powered tests. As predicted, a newly constructed and pre-registered measure derived from preschool delay of gratification does not predict the 11 capital formation variables (i.e., the sign-adjusted average correlation was 0.02). A pre-registered composite self-regulation index, combining preschool delay of gratification with survey measures of self-regulation collected at ages 17, 27, and 37, does predict 10 of the 11 capital formation variables in the expected direction, with an average correlation of 0.19. The inclusion of the preschool delay of gratification measure in this composite index does not affect the index's predictive power. We tested several hypothesized reasons that preschool delay of gratification does not have predictive power for our mid-life capital formation variables.

Journal of economic behavior & organization · 10 citationsread the source →