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Comparison of behavioural activation with guided self-help for treatment of depression in adults with intellectual disabilities: a randomised controlled trial.

Background: Psychological therapies are first-line interventions for depression, but existing provision is not accessible for many adults with intellectual disabilities. We investigated the clinical and cost-effectiveness of a behavioural activation intervention (BeatIt) for people with intellectual disabilities and depression. BeatIt was compared with a guided self-help intervention (StepUp). Methods: We did a multicentre, single-blind, randomised, controlled trial with follow-up at 4 months and 12 months after randomisation. Participants aged 18 years or older, with mild to moderate intellectual disabilities and clinically significant depression were recruited from health and social care services in the UK. The primary outcome was the Glasgow Depression Scale for people with a Learning Disability (GDS-LD) score at 12 months. Analyses were done on an intention-to-treat basis. This trial is registered with ISCRTN, number ISRCTN09753005. Findings: Between Aug 8, 2013, and Sept 1, 2015, 161 participants were randomly assigned (84 to BeatIt; 77 to StepUp); 141 (88%) participants completed the trial. No group differences were found in the effects of BeatIt and StepUp based on GDS-LD scores at 12 months (12·03 [SD 7·99] GDS-LD points for BeatIt vs 12·43 [SD 7·64] GDS-LD points for StepUp; mean difference 0·26 GDS-LD points [95% CI -2·18 to 2·70]; p=0·833). Within-group improvements in GDS-LD scores occurred in both groups at 12 months (BeatIt, mean change -4·2 GDS-LD points [95% CI -6·0 to -2·4], p<0·0001; StepUp, mean change -4·5 GDS-LD points [-6·2 to -2·7], p<0·0001), with large effect sizes (BeatIt, 0·590 [95% CI 0·337-0·844]; StepUp, 0·627 [0·380-0·873]). BeatIt was not cost-effective when compared with StepUp, although the economic analyses indicated substantial uncertainty. Treatment costs were only approximately 3·6-6·8% of participants' total support costs. No treatment-related or trial-related adverse events were reported. Interpretation: This study is, to our knowledge, the first large randomised controlled trial assessing individual psychological interventions for people with intellectual disabilities and mental health problems. These findings show that there is no evidence that BeatIt is more effective than StepUp; both are active and potentially effective interventions. Funding: National Institute for Health Research.

The lancet. Psychiatry · randomised controlled trial · 49 citationsread the source →

The impact of adult behavioural weight management interventions on mental health: A systematic review and meta-analysis.

There is good evidence that behavioural weight management interventions improve physical health; however, the impact on mental health remains unclear. We evaluated the impact of behavioural weight management interventions on mental health-related outcomes in adults with overweight or obesity at intervention-end and 12 months from baseline. Eligible studies were randomized controlled trials (RCTs) or cluster RCTs of adult behavioural weight loss interventions reporting affect, anxiety, binge eating, body image, depression, emotional eating, quality of life, self-esteem and stress. We searched seven databases from inception to 7 May 2019 and included 43 articles reporting 42 RCTs. Eighteen studies were deemed to be at high risk of bias. We conducted random-effects meta-analyses, stratified analyses and meta-regression using Stata. Interventions generated greater improvements than comparators for depression, mental health-related quality of life and self-efficacy at intervention-end and 12 months from baseline. There was no difference between groups for anxiety, overall quality of life, self-esteem or stress at intervention-end. There was insufficient evidence to assess the impact on anxiety, binge eating, body image, emotional eating, affect, life satisfaction, self-esteem or stress at intervention-end and/or 12 months from baseline. Although evidence suggests that interventions benefit some aspects of mental health, high-quality, transparently reported RCTs measuring a range of mental health outcomes over longer durations are required to strengthen the evidence base.

Obesity reviews : an official journal of the International Association for the Study of Obesity · meta-analysis · 62 citationsread the source →

Effect of sleep duration on dietary intake, desire to eat, measures of food intake and metabolic hormones: A systematic review of clinical trials.

Background and aims: Sleep, as well as diet and physical activity, plays a significant role in growth, maturation, health, and regulation of energy homeostasis. Recently, there is increasing evidence indicating a possible causal association between sleep duration and energy balance. We aimed to examine the relationship between sleep duration and food consumption, energy intake, anthropometric characteristics, and appetite-regulating hormones by randomized controlled trials (RCTs). Methods: Electronic literature searches were conducted on Medline, Web of Science, and Google Scholar until July 2020. The search was conducted with the following words: "Sleep Duration", "Circadian Rhythm", "Sleep Disorders" in combination with "Obesity", "Overweight", "Abdominal Obesity", "Physical Activity", "Energy Intake", "Body Mass Index", "Lipid Metabolism", "Caloric Restriction", Leptin, "Weight Gain", and "Appetite Regulation" using human studies.methods RESULTS: After screening 708 abstracts, 50 RCTs (7 on children or adolescents and 43 on adults) were identified and met the inclusion criteria. In general, the findings suggested that sleep restriction may leads to a significant increment in energy intake, fat intake, body weight, appetite, hunger, eating occasions, and portion size, while protein and carbohydrate consumption, total energy expenditure, and respiratory quotient remained unaffected as a result of sleep restriction. Serum leptin, ghrelin, and cortisol concentrations were not influenced by sleep duration as well. Conclusion: Insufficient sleep can be considered as a contributing factor for energy imbalance, weight gain, and metabolic disorders and it is suggested that to tackle disordered eating it may be necessary to pay more attention to sleep duration.

Clinical nutrition ESPEN · systematic review · 28 citationsread the source →

Family-centered advance care planning for teens with cancer.

Importance: Advance care planning (ACP) prepares patients and their families for future health care decisions; however, the needs of adolescent oncology patients for participation in ACP have not been well studied. Objective: To examine the efficacy of family-centered ACP. Design and setting: Two-group randomized controlled trial in a pediatric oncology program. Participants: Sixty adolescents aged 14 to 21 years with cancer and their surrogates or families were enrolled in the study between January 17, 2011, and March 29, 2012. Intervention: Thirty dyads received 3- to 60-minute sessions 1 week apart. Intervention dyads completed (1) the Lyon Family-Centered ACP Survey, (2) the Respecting Choices interview, and (3) Five Wishes. Control subjects received standard care plus information. Main outcome measures: Statement of treatment preferences and Decisional Conflict Scale score. Results: The mean age of the adolescents was 16 years; 36 (60%) were male, 30 (50%) white, 26 (43%) black, and 4 (7%) Asian. Diagnoses were as follows: leukemia (14 patients [47%]), brain tumor (8 [27%]), solid tumor (6 [20%]), and lymphoma (2 [7%]). Significantly increased congruence was observed for intervention dyads compared with controls for 4 of the 6 disease-specific scenarios; for example, for situation 2 ("treatment would extend my life by not more than 2 to 3 months"), intervention dyads demonstrated higher congruence (κ = 0.660; P < .001) vs control dyads (κ = -0.0636; P = .70). Intervention adolescents (100%) wanted their families to do what is best at the time, whereas fewer control adolescents (62%) gave families this leeway. Intervention adolescents were significantly better informed about end-of-life decisions (t = 2.93; effect size, 0.961; 95% CI, 0.742-1.180; P = .007). Intervention families were more likely to concur on limiting treatments than controls. An ethnic difference was found in only one situation. Conclusions: Advance care planning enabled families to understand and honor their adolescents' wishes. Intervention dyads were more likely than controls to limit treatments. Underserved African American families were willing to participate.

JAMA pediatrics · randomised controlled trial · 149 citationsread the source →

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

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

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

Cancer mortality in India: a nationally representative survey.

Background: The age-specific mortality rates and total deaths from specific cancers have not been documented for the various regions and subpopulations of India. We therefore assessed the cause of death in 2001-03 in homes in small areas that were chosen to be representative of all the parts of India. Methods: At least 130 trained physicians independently assigned causes to 122,429 deaths, which occurred in 1·1 million homes in 6671 small areas that were randomly selected to be representative of all of India, based on a structured non-medical surveyor's field report. Findings: 7137 of 122,429 study deaths were due to cancer, corresponding to 556,400 national cancer deaths in India in 2010. 395,400 (71%) cancer deaths occurred in people aged 30-69 years (200,100 men and 195,300 women). At 30-69 years, the three most common fatal cancers were oral (including lip and pharynx, 45,800 [22·9%]), stomach (25,200 [12·6%]), and lung (including trachea and larynx, 22,900 [11·4%]) in men, and cervical (33,400 [17·1%]), stomach (27,500 [14·1%]), and breast (19,900 [10·2%]) in women. Tobacco-related cancers represented 42·0% (84,000) of male and 18·3% (35,700) of female cancer deaths and there were twice as many deaths from oral cancers as lung cancers. Age-standardised cancer mortality rates per 100,000 were similar in rural (men 95·6 [99% CI 89·6-101·7] and women 96·6 [90·7-102·6]) and urban areas (men 102·4 [92·7-112·1] and women 91·2 [81·9-100·5]), but varied greatly between the states, and were two times higher in the least educated than in the most educated adults (men, illiterate 106·6 [97·4-115·7] vs most educated 45·7 [37·8-53·6]; women, illiterate 106·7 [99·9-113·6] vs most educated 43·4 [30·7-56·1]). Cervical cancer was far less common in Muslim than in Hindu women (study deaths 24, age-standardised mortality ratio 0·68 [0·64-0·71] vs 340, 1·06 [1·05-1·08]). Interpretation: Prevention of tobacco-related and cervical cancers and earlier detection of treatable cancers would reduce cancer deaths in India, particularly in the rural areas that are underserved by cancer services. The substantial variation in cancer rates in India suggests other risk factors or causative agents that remain to be discovered. Funding: Bill & Melinda Gates Foundation and US National Institutes of Health.

Lancet (London, England) · 296 citationsread the source →

Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: a randomised controlled, open-label, multicentre trial.

Background: Treatment of patients with ileocaecal Crohn's disease who have not responded to conventional therapy is commonly scaled up to biological agents, but surgery can also offer excellent short-term and long-term results. We compared laparoscopic ileocaecal resection with infliximab to assess how they affect health-related quality of life. Methods: In this randomised controlled, open-label trial, in 29 teaching hospitals and tertiary care centres in the Netherlands and the UK, adults with non-stricturing, ileocaecal Crohn's disease, in whom conventional therapy has failed were randomly allocated (1:1) by an internet randomisation module with biased-coin minimisation for participating centres and perianal fistula to receive laparoscopic ileocaecal resection or infliximab. Eligible patients were aged 18-80 years, had active Crohn's disease of the terminal ileum, and had not responded to at least 3 months of conventional therapy with glucocorticosteroids, thiopurines, or methotrexate. Patients with diseased terminal ileum longer than 40 cm or abdominal abscesses were excluded. The primary outcome was quality of life on the Inflammatory Bowel Disease Questionnaire (IBDQ) at 12 months. Secondary outcomes were general quality of life, measured by the Short Form-36 (SF-36) health survey and its physical and mental component subscales, days unable to participate in social life, days on sick leave, morbidity (additional procedures and hospital admissions), and body image and cosmesis. Analyses of the primary outcome were done in the intention-to-treat population, and safety analyses were done in the per-protocol population. This trial is registered at the Dutch Trial Registry (NTR1150). Findings: Between May 2, 2008, and October 14, 2015, 73 patients were allocated to have resection and 70 to receive infliximab. Corrected for baseline differences, the mean IBDQ score at 12 months was 178·1 (95% CI 171·1-185·0) in the resection group versus 172·0 (164·3-179·6) in the infliximab group (mean difference 6·1 points, 95% CI -4·2 to 16·4; p=0·25). At 12 months, the mean SF-36 total score was 112·1 (95% CI 108·0-116·2) in the resection group versus 106·5 (102·1-110·9) in the infliximab group (mean difference 5·6, 95% CI -0·4 to 11·6), the mean physical component score was 47·7 (45·7-49·7) versus 44·6 (42·5-46·8; mean difference 3·1, 4·2 to 6·0), and the mean mental component score was 49·5 (47·0-52·1) versus 46·1 (43·3-48·9; mean difference 3·5, -0·3 to 7·3). Mean numbers of days of sick leave were 3·4 days (SD 7·1) in the resection group versus 1·4 days (4·7) in the infliximab group (p<0·0001), days not able to take part in social life were 1·8 days (6·3) versus 1·1 days (4·5; p=0·20), days of scheduled hospital admission were 6·5 days (3·8) versus 6·8 days (3·2; p=0·84), and the number of patients who had unscheduled hospital admissions were 13 (18%) of 73 versus 15 (21%) of 70 (p=0·68). Body-image scale mean scores in the patients who had resection were 16·0 (95% CI 15·2-16·8) at baseline versus 17·8 (17·1-18·4) at 12 months, and cosmetic scale mean scores were 17·6 (16·6-18·6) versus 18·6 (17·6-19·6). Surgical intervention-related complications classified as IIIa or worse on the Clavien-Dindo scale occurred in four patients in the resection group. Treatment-related serious adverse events occurred in two patients in the infliximab group. During a median follow-up of 4 years (IQR 2-6), 26 (37%) of 70 patients in the infliximab group had resection, and 19 (26%) of 73 patients in the resection group received anti-TNF. Interpretation: Laparoscopic resection in patients with limited (diseased terminal ileum <40 cm), non-stricturing, ileocaecal Crohn's disease in whom conventional therapy has failed could be considered a reasonable alternative to infliximab therapy. Funding: Netherlands Organisation for Health Research and Development.

The lancet. Gastroenterology & hepatology · randomised controlled trial · 228 citationsread the source →

Comparison of paediatric emergency department visits for attempted suicide, self-harm, and suicidal ideation before and during the COVID-19 pandemic: a systematic review and meta-analysis.

Background: There is a lack of consensus about the effect of the COVID-19 pandemic on the mental health of children and adolescents. We aimed to compare rates of paediatric emergency department visits for attempted suicide, self-harm, and suicidal ideation during the pandemic with those before the pandemic. Methods: For this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO for studies published between Jan 1, 2020, and Dec 19, 2022. Studies published in English with data on paediatric (ie, those aged <19 years) emergency department visits before and during the COVID-19 pandemic were included. Case studies and qualitative analyses were excluded. Changes in attempted suicide, self-harm, suicidal ideation, and other mental-illness indicators (eg, anxiety, depression, and psychosis) were expressed as ratios of the rates of emergency department visits during the pandemic compared with those before the pandemic, and we analysed these with a random-effects meta-analysis. This study was registered with PROSPERO, CRD42022341897. Findings: 10 360 non-duplicate records were retrieved, which yielded 42 relevant studies (with 130 sample-estimates) representing 11·1 million emergency department visits for all indications of children and adolescents across 18 countries. The mean age of the samples of children and adolescents across studies was 11·7 years (SD 3·1, range 5·5-16·3), and there were on average 57·6% girls and 43·4% boys as a proportion of emergency department visits for any health reasons (ie, physical and mental). Only one study had data related to race or ethnicity. There was good evidence of an increase in emergency department visits for attempted suicide during the pandemic (rate ratio 1·22, 90% CI 1·08-1·37), modest evidence of an increase in emergency department visits for suicidal ideation (1·08, 0·93-1·25), and good evidence for only a slight change in self-harm (0·96, 0·89-1·04). Rates of emergency department visits for other mental-illness indications showed very good evidence of a decline (0·81, 0·74-0·89), and paediatric visits for all health indications showed strong evidence of a reduction (0·68, 0·62-0·75). When rates for attempted suicide and suicidal ideation were combined as a single measure, there was good evidence of an increase in emergency department visits among girls (1·39, 1·04-1·88) and only modest evidence of an increase among boys (1·06, 0·92-1·24). Self-harm among older children (mean age 16·3 years, range 13·0-16·3) showed good evidence of an increase (1·18, 1·00-1·39), but among younger children (mean age 9·0 years, range 5·5-12·0) there was modest evidence of a decrease (0·85, 0·70-1·05). Interpretation: The integration of mental health support within community health and the education system-including promotion, prevention, early intervention, and treatment-is urgently needed to increase the reach of mental health support that can mitigate child and adolescent mental distress. In future pandemics, increased resourcing in some emergency department settings would help to address their expected increase in visits for acute mental distress among children and adolescents. Funding: None.

The lancet. Psychiatry · meta-analysis · 164 citationsread the source →

Cognitive behavioural therapy for tinnitus.

Background: Tinnitus affects up to 21% of the adult population with an estimated 1% to 3% experiencing severe problems. Cognitive behavioural therapy (CBT) is a collection of psychological treatments based on the cognitive and behavioural traditions in psychology and often used to treat people suffering from tinnitus. Objectives: To assess the effects and safety of CBT for tinnitus in adults. Search methods: The Cochrane ENT Information Specialist searched the ENT Trials Register; CENTRAL (2019, Issue 11); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 25 November 2019. Selection criteria: Randomised controlled trials (RCTs) of CBT versus no intervention, audiological care, tinnitus retraining therapy or any other active treatment in adult participants with tinnitus. Data collection and analysis: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were the impact of tinnitus on disease-specific quality of life and serious adverse effects. Our secondary outcomes were: depression, anxiety, general health-related quality of life, negatively biased interpretations of tinnitus and other adverse effects. We used GRADE to assess the certainty of evidence for each outcome. Main results: We included 28 studies (mostly from Europe) with a total of 2733 participants. All participants had had tinnitus for at least three months and their average age ranged from 43 to 70 years. The duration of the CBT ranged from 3 to 22 weeks and it was mostly conducted in hospitals or online. There were four comparisons and we were interested in outcomes at end of treatment, and 6 and 12 months follow-up. The results below only refer to outcomes at end of treatment due to an absence of evidence at the other follow-up time points. CBT versus no intervention/wait list control Fourteen studies compared CBT with no intervention/wait list control. For the primary outcome, CBT may reduce the impact of tinnitus on quality of life at treatment end (standardised mean difference (SMD) -0.56, 95% confidence interval (CI) -0.83 to -0.30; 10 studies; 537 participants; low certainty). Re-expressed as a score on the Tinnitus Handicap Inventory (THI; range 0 to 100) this is equivalent to a score 10.91 points lower in the CBT group, with an estimated minimal clinically important difference (MCID) for this scale being 7 points. Seven studies, rated as moderate certainty, either reported or informed us via personal communication about serious adverse effects. CBT probably results in little or no difference in adverse effects: six studies reported none and in one study one participant in the CBT condition worsened (risk ratio (RR) 3.00, 95% CI 0.13 to 69.87). For the secondary outcomes, CBT may result in a slight reduction in depression (SMD -0.34, 95% CI-0.60 to -0.08; 8 studies; 502 participants; low certainty). However, we are uncertain whether CBT reduces anxiety, improves health-related quality of life or reduces negatively biased interpretations of tinnitus (all very low certainty). From seven studies, no other adverse effects were reported (moderate certainty). CBT versus audiological care Three studies compared CBT with audiological care. CBT probably reduces the impact of tinnitus on quality of life when compared with audiological care as measured by the THI (range 0 to 100; mean difference (MD) -5.65, 95% CI -9.79 to -1.50; 3 studies; 444 participants) (moderate certainty; MCID = 7 points). No serious adverse effects occurred in the two included studies reporting these, thus risk ratios were not calculated (moderate certainty). The evidence suggests that CBT may slightly reduce depression but may result in little or no difference in anxiety or health-related quality of life (all low certainty) when compared with audiological care. CBT may reduce negatively biased interpretations of tinnitus when compared with audiological care (low certainty). No other adverse effects were reported for either group (moderate certainty). CBT versus tinnitus retraining therapy (TRT) One study compared CBT with TRT (including bilateral sound generators as per TRT protocol). CBT may reduce the impact of tinnitus on quality of life as measured by the THI when compared with TRT (range 0 to 100) (MD -15.79, 95% CI -27.91 to -3.67; 1 study; 42 participants; low certainty). For serious adverse effects three participants deteriorated during the study: one in the CBT (n = 22) and two in the TRT group (n = 20) (RR 0.45, 95% CI 0.04 to 4.64; low certainty). We are uncertain whether CBT reduces depression and anxiety or improves health-related quality of life (low certainty). CBT may reduce negatively biased interpretations of tinnitus. No data were available for other adverse effects. CBT versus other active control Sixteen studies compared CBT with another active control (e.g. relaxation, information, Internet-based discussion forums). CBT may reduce the impact of tinnitus on quality of life when compared with other active treatments (SMD -0.30, 95% CI -0.55 to -0.05; 12 studies; 966 participants; low certainty). Re-expressed as a THI score this is equivalent to 5.84 points lower in the CBT group than the other active control group (MCID = 7 points). One study reported that three participants deteriorated: one in the CBT and two in the information only group (RR 1.70, 95% CI 0.16 to 18.36; low certainty). CBT may reduce depression and anxiety (both low certainty). We are uncertain whether CBT improves health-related quality of life compared with other control. CBT probably reduces negatively biased interpretations of tinnitus compared with other treatments. No data were available for other adverse effects. Authors' conclusions: CBT may be effective in reducing the negative impact that tinnitus can have on quality of life. There is, however, an absence of evidence at 6 or 12 months follow-up. There is also some evidence that adverse effects may be rare in adults with tinnitus receiving CBT, but this could be further investigated. CBT for tinnitus may have small additional benefit in reducing symptoms of depression although uncertainty remains due to concerns about the quality of the evidence. Overall, there is limited evidence for CBT for tinnitus improving anxiety, health-related quality of life or negatively biased interpretations of tinnitus.

The Cochrane database of systematic reviews · meta-analysis · 131 citationsread the source →

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

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

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

Ramadan Fasting during Pregnancy and Health Outcomes in Offspring: A Systematic Review.

Ramadan is one of the five pillars of Islam, during which fasting is obligatory for all healthy individuals. Although pregnant women are exempt from this Islamic law, the majority nevertheless choose to fast. This review aims to identify the effects of Ramadan fasting on the offspring of Muslim mothers, particularly on fetal growth, birth indices, cognitive effects and long-term effects. A systematic literature search was conducted until March 2020 in Web of Science, Pubmed, Cochrane Library, Embase and Google Scholar. Studies were evaluated based on a pre-defined quality score ranging from 0 (low quality) to 10 (high quality), and 43 articles were included. The study quality ranged from 2 to 9 with a mean quality score of 5.4. Only 3 studies had a high quality score (>7), of which one found a lower birth weight among fasting women. Few medium quality studies found a significant negative effect on fetal growth or birth indices. The quality of articles that investigated cognitive and long-term effects was poor. The association between Ramadan fasting and health outcomes of offspring is not supported by strong evidence. To further elucidate the effects of Ramadan fasting, larger prospective and retrospective studies with novel designs are needed.

Nutrients · systematic review · 19 citationsread the source →

Global, regional, and national incidence and mortality burden of non-COVID-19 lower respiratory infections and aetiologies, 1990-2021: a systematic analysis from the Global Burden of Disease Study 2021.

Background: Lower respiratory infections (LRIs) are a major global contributor to morbidity and mortality. In 2020-21, non-pharmaceutical interventions associated with the COVID-19 pandemic reduced not only the transmission of SARS-CoV-2, but also the transmission of other LRI pathogens. Tracking LRI incidence and mortality, as well as the pathogens responsible, can guide health-system responses and funding priorities to reduce future burden. We present estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 of the burden of non-COVID-19 LRIs and corresponding aetiologies from 1990 to 2021, inclusive of pandemic effects on the incidence and mortality of select respiratory viruses, globally, regionally, and for 204 countries and territories. Methods: We estimated mortality, incidence, and aetiology attribution for LRI, defined by the GBD as pneumonia or bronchiolitis, not inclusive of COVID-19. We analysed 26 259 site-years of mortality data using the Cause of Death Ensemble model to estimate LRI mortality rates. We analysed all available age-specific and sex-specific data sources, including published literature identified by a systematic review, as well as household surveys, hospital admissions, health insurance claims, and LRI mortality estimates, to generate internally consistent estimates of incidence and prevalence using DisMod-MR 2.1. For aetiology estimation, we analysed multiple causes of death, vital registration, hospital discharge, microbial laboratory, and literature data using a network analysis model to produce the proportion of LRI deaths and episodes attributable to the following pathogens: Acinetobacter baumannii, Chlamydia spp, Enterobacter spp, Escherichia coli, fungi, group B streptococcus, Haemophilus influenzae, influenza viruses, Klebsiella pneumoniae, Legionella spp, Mycoplasma spp, polymicrobial infections, Pseudomonas aeruginosa, respiratory syncytial virus (RSV), Staphylococcus aureus, Streptococcus pneumoniae, and other viruses (ie, the aggregate of all viruses studied except influenza and RSV), as well as a residual category of other bacterial pathogens. Findings: Globally, in 2021, we estimated 344 million (95% uncertainty interval [UI] 325-364) incident episodes of LRI, or 4350 episodes (4120-4610) per 100 000 population, and 2·18 million deaths (1·98-2·36), or 27·7 deaths (25·1-29·9) per 100 000. 502 000 deaths (406 000-611 000) were in children younger than 5 years, among which 254 000 deaths (197 000-320 000) occurred in countries with a low Socio-demographic Index. Of the 18 modelled pathogen categories in 2021, S pneumoniae was responsible for the highest proportions of LRI episodes and deaths, with an estimated 97·9 million (92·1-104·0) episodes and 505 000 deaths (454 000-555 000) globally. The pathogens responsible for the second and third highest episode counts globally were other viral aetiologies (46·4 million [43·6-49·3] episodes) and Mycoplasma spp (25·3 million [23·5-27·2]), while those responsible for the second and third highest death counts were S aureus (424 000 [380 000-459 000]) and K pneumoniae (176 000 [158 000-194 000]). From 1990 to 2019, the global all-age non-COVID-19 LRI mortality rate declined by 41·7% (35·9-46·9), from 56·5 deaths (51·3-61·9) to 32·9 deaths (29·9-35·4) per 100 000. From 2019 to 2021, during the COVID-19 pandemic and implementation of associated non-pharmaceutical interventions, we estimated a 16·0% (13·1-18·6) decline in the global all-age non-COVID-19 LRI mortality rate, largely accounted for by a 71·8% (63·8-78·9) decline in the number of influenza deaths and a 66·7% (56·6-75·3) decline in the number of RSV deaths. Interpretation: Substantial progress has been made in reducing LRI mortality, but the burden remains high, especially in low-income and middle-income countries. During the COVID-19 pandemic, with its associated non-pharmaceutical interventions, global incident LRI cases and mortality attributable to influenza and RSV declined substantially. Expanding access to health-care services and vaccines, including S pneumoniae, H influenzae type B, and novel RSV vaccines, along with new low-cost interventions against S aureus, could mitigate the LRI burden and prevent transmission of LRI-causing pathogens. Funding: Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care (UK).

The Lancet. Infectious diseases · systematic review · 388 citationsread the source →

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

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

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

Prevalence of Health Misinformation on Social Media: Systematic Review.

Background: Although at present there is broad agreement among researchers, health professionals, and policy makers on the need to control and combat health misinformation, the magnitude of this problem is still unknown. Consequently, it is fundamental to discover both the most prevalent health topics and the social media platforms from which these topics are initially framed and subsequently disseminated. Objective: This systematic review aimed to identify the main health misinformation topics and their prevalence on different social media platforms, focusing on methodological quality and the diverse solutions that are being implemented to address this public health concern. Methods: We searched PubMed, MEDLINE, Scopus, and Web of Science for articles published in English before March 2019, with a focus on the study of health misinformation in social media. We defined health misinformation as a health-related claim that is based on anecdotal evidence, false, or misleading owing to the lack of existing scientific knowledge. We included (1) articles that focused on health misinformation in social media, including those in which the authors discussed the consequences or purposes of health misinformation and (2) studies that described empirical findings regarding the measurement of health misinformation on these platforms. Results: A total of 69 studies were identified as eligible, and they covered a wide range of health topics and social media platforms. The topics were articulated around the following six principal categories: vaccines (32%), drugs or smoking (22%), noncommunicable diseases (19%), pandemics (10%), eating disorders (9%), and medical treatments (7%). Studies were mainly based on the following five methodological approaches: social network analysis (28%), evaluating content (26%), evaluating quality (24%), content/text analysis (16%), and sentiment analysis (6%). Health misinformation was most prevalent in studies related to smoking products and drugs such as opioids and marijuana. Posts with misinformation reached 87% in some studies. Health misinformation about vaccines was also very common (43%), with the human papilloma virus vaccine being the most affected. Health misinformation related to diets or pro-eating disorder arguments were moderate in comparison to the aforementioned topics (36%). Studies focused on diseases (ie, noncommunicable diseases and pandemics) also reported moderate misinformation rates (40%), especially in the case of cancer. Finally, the lowest levels of health misinformation were related to medical treatments (30%). Conclusions: The prevalence of health misinformation was the highest on Twitter and on issues related to smoking products and drugs. However, misinformation on major public health issues, such as vaccines and diseases, was also high. Our study offers a comprehensive characterization of the dominant health misinformation topics and a comprehensive description of their prevalence on different social media platforms, which can guide future studies and help in the development of evidence-based digital policy action plans.

Journal of medical Internet research · systematic review · 808 citationsread the source →

Exercise as adjunctive therapy for systemic lupus erythematosus.

Background: Systemic lupus erythematosus (SLE) is a rare, chronic autoimmune inflammatory disease with a prevalence varying from 4.3 to 150 people in 100,000, or approximately five million people worldwide. Systemic manifestations frequently include internal organ involvement, a characteristic malar rash on the face, pain in joints and muscles, and profound fatigue. Exercise is purported to be beneficial for people with SLE. For this review, we focused on studies that examined all types of structured exercise as an adjunctive therapy in the management of SLE. Objectives: To evaluate the benefits and harms of structured exercise as adjunctive therapy for adults with SLE compared with usual pharmacological care, usual pharmacological care plus placebo and usual pharmacological care plus non-pharmacological care. Search methods: We used standard, extensive Cochrane search methods. The latest search date was 30 March 2022. Selection criteria: We included randomised controlled trials (RCTs) of exercise as an adjunct to usual pharmacological treatment in SLE compared with placebo, usual pharmacological care alone and another non-pharmacological treatment. Major outcomes were fatigue, functional capacity, disease activity, quality of life, pain, serious adverse events, and withdrawals due to any reason, including any adverse events. Data collection and analysis: We used standard Cochrane methods. Our major outcomes were 1. fatigue, 2. functional capacity, 3. disease activity, 4. quality of life, 5. pain, 6. serious adverse events, and 7. withdrawals due to any reason. Our minor outcomes were 8. responder rate, 9. aerobic fitness, 10. depression, and 11. anxiety. We used GRADE to assess certainty of evidence. The primary comparison was exercise compared with placebo. Main results: We included 13 studies (540 participants) in this review. Studies compared exercise as an adjunct to usual pharmacological care (antimalarials, immunosuppressants, and oral glucocorticoids) with usual pharmacological care plus placebo (one study); usual pharmacological care (six studies); and another non-pharmacological treatment such as relaxation therapy (seven studies). Most studies had selection bias, and all studies had performance and detection bias. We downgraded the evidence for all comparisons because of a high risk of bias and imprecision. Exercise plus usual pharmacological care versus placebo plus usual pharmacological care Evidence from a single small study (17 participants) that compared whole body vibration exercise to whole body placebo vibration exercise (vibrations switched off) indicated that exercise may have little to no effect on fatigue, functional capacity, and pain (low-certainty evidence). We are uncertain whether exercise results in fewer or more withdrawals (very low-certainty evidence). The study did not report disease activity, quality of life, and serious adverse events. The study measured fatigue using the self-reported Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue), scale 0 to 52; lower score means less fatigue. People who did not exercise rated their fatigue at 38 points and those who did exercise rated their fatigue at 33 points (mean difference (MD) 5 points lower, 95% confidence interval (CI) 13.29 lower to 3.29 higher). The study measured functional capacity using the self-reported 36-item Short Form health questionnaire (SF-36) Physical Function domain, scale 0 to 100; higher score means better function. People who did not exercise rated their functional capacity at 70 points and those who did exercise rated their functional capacity at 67.5 points (MD 2.5 points lower, 95% CI 23.78 lower to 18.78 higher). The study measured pain using the SF-36 Pain domain, scale 0 to 100; lower scores mean less pain. People who did not exercise rated their pain at 43 points and those who did exercise rated their pain at 34 points (MD 9 points lower, 95% CI 28.88 lower to 10.88 higher). More participants from the exercise group (3/11, 27%) withdrew from the study than the placebo group (1/10, 10%) (risk ratio (RR) 2.73, 95% CI 0.34 to 22.16). Exercise plus usual pharmacological care versus usual pharmacological care alone The addition of exercise to usual pharmacological care may have little to no effect on fatigue, functional capacity, and disease activity (low-certainty evidence). We are uncertain whether the addition of exercise improves pain (very low-certainty evidence), or results in fewer or more withdrawals (very low-certainty evidence). Serious adverse events and quality of life were not reported. Exercise plus usual care versus another non-pharmacological intervention such as receiving information about the disease or relaxation therapy Compared with education or relaxation therapy, exercise may reduce fatigue slightly (low-certainty evidence), may improve functional capacity (low-certainty evidence), probably results in little to no difference in disease activity (moderate-certainty evidence), and may result in little to no difference in pain (low-certainty evidence). We are uncertain whether exercise results in fewer or more withdrawals (very low-certainty evidence). Quality of life and serious adverse events were not reported. Authors' conclusions: Due to low- to very low-certainty evidence, we are not confident on the benefits of exercise on fatigue, functional capacity, disease activity, and pain, compared with placebo, usual care, or advice and relaxation therapy. Harms data were not well reported.

The Cochrane database of systematic reviews · systematic review · 11 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 →

Cost-effectiveness and economic returns of group-based parenting interventions to promote early childhood development: Results from a randomized controlled trial in rural Kenya.

Background: Early childhood development (ECD) programs can help address disadvantages for the 43% of children under 5 in low- and middle-income countries (LMICs) experiencing compromised development. However, very few studies from LMIC settings include information on their program's cost-effectiveness or potential returns to investment. We estimated the cost-effectiveness, benefit-cost ratios (BCRs), and returns on investment (ROIs) for 2 effective group-based delivery models of an ECD parenting intervention that utilized Kenya's network of local community health volunteers (CHVs). Methods and findings: Between October 1 and November 12, 2018, 1,152 mothers with children aged 6 to 24 months were surveyed from 60 villages in rural western Kenya. After baseline, villages were randomly assigned to one of 3 intervention arms: a group-only delivery model with 16 fortnightly sessions, a mixed-delivery model combining 12 group sessions with 4 home visits, and a control group. At endline (August 5 to October 31, 2019), 1,070 children were retained and assessed for primary outcomes including cognitive and receptive language development (with the Bayley Scales of Infant Development, Third Edition) and socioemotional development (with the Wolke scale). Children in the 2 intervention arms showed better developmental outcomes than children in the control arm, although the group-only delivery model generally had larger effects on children. Total program costs included provider's implementation costs collected during the intervention period using financial reports from the local nongovernmental organization (NGO) implementer, as well as societal costs such as opportunity costs to mothers and delivery agents. We combined program impacts with these total costs to estimate incremental cost-effectiveness ratios (ICERs), as well as BCRs and the program's ROI for the government based on predictions of future lifetime wages and societal costs. Total costs per child were US$140 in the group-only arm and US$145 in the mixed-delivery arm. Because of higher intention-to-treat (ITT) impacts at marginally lower costs, the group-only model was the most cost-effective across all child outcomes. Focusing on child cognition in this arm, we estimated an ICER of a 0.37 standard deviation (SD) improvement in cognition per US$100 invested, a BCR of 15.5, and an ROI of 127%. A limitation of our study is that our estimated BCR and ROI necessarily make assumptions about the discount rate, income tax rates, and predictions of intervention impacts on future wages and schooling. We examine the sensitivity of our results to these assumptions. Conclusions: To the best of our knowledge, this study is the first economic evaluation of an effective ECD parenting intervention targeted to young children in sub-Saharan Africa (SSA) and the first to adopt a societal perspective in calculating cost-effectiveness that accounts for opportunity costs to delivery agents and program participants. Our cost-effectiveness and benefit-cost estimates are higher than most of the limited number of prior studies from LMIC settings providing information about costs. Our results represent a strong case for scaling similar interventions in impoverished rural settings, and, under reasonable assumptions about the future, demonstrate that the private and social returns of such investments are likely to largely outweigh their costs. Trial registration: This trial is registered at ClinicalTrials.gov, NCT03548558, June 7, 2018. American Economic Association RCT Registry trial AEARCTR-0002913.

PLoS medicine · randomised controlled trial · 24 citationsread the source →

Adoption, reach, and implementation of a cancer education intervention in African American churches.

Background: Use of technology is increasing in health promotion and has continued growth potential in intervention research. Guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, this paper reports on the adoption, reach, and implementation of Project HEAL (Health through Early Awareness and Learning)-a community-based implementation trial of a cancer educational intervention in 14 African American churches. We compare adoption, reach, and implementation at the organizational and participant level for churches in which lay peer community health advisors (CHAs) were trained using traditional classroom didactic methods compared with a new online system. Methods: Fifteen churches were randomized to one of two study groups in which two CHAs per church were trained through either classroom ("Traditional"; n = 16 CHAs in 8 churches) or web-based ("Technology"; n = 14 CHAs in 7 churches) training methods. Once trained and certified, all CHAs conducted a series of three group educational workshops in their churches on cancer early detection (breast, prostate, and colorectal). Adoption, reach, and implementation were assessed using multiple data sources including church-level data, participant engagement in the workshops, and study staff observations of CHA performance. Results: The project had a 41% overall adoption rate at the church level. In terms of reach, a total of 375 participants enrolled in Project HEAL-226 participants in the Traditional group (43% reach) and 149 in the Technology group (21% reach; p < .10). Implementation was evaluated in terms of adherence, dosage, and quality. All churches fully completed the three workshops; however, the Traditional churches took somewhat longer (M = 84 days) to complete the workshop series than churches in the Technology group (M = 64 days). Other implementation outcomes were comparable between both the Traditional and Technology groups (p > .05). Conclusions: Overall, the Project HEAL intervention had reasonable adoption, though reach could have been better. Implementation was strong across both study groups, suggesting the promise of using web-based methods to disseminate and implement evidence-based interventions in faith-based settings and other areas where community health educators work to eliminate health disparities.

Implementation science : IS · randomised controlled trial · 40 citationsread the source →

Mindful gratitude journaling: psychological distress, quality of life and suffering in advanced cancer: a randomised controlled trial.

Context: Numerous studies have shown that gratitude can reduce stress and improve quality of life. Objective: Our study aimed to examine the effect of mindful gratitude journaling on suffering, psychological distress and quality of life of patients with advanced cancer. Methods: We conducted a parallel-group, blinded, randomised controlled trial at the University of Malaya Medical Centre, Malaysia. Ninety-two adult patients with advanced cancer, and an overall suffering score ≥4/10 based on the Suffering Pictogram were recruited and randomly assigned to either a mindful gratitude journaling group (N=49) or a routine journaling group (N=43). Results: After 1 week, there were significant reductions in the overall suffering score from the baseline in both the intervention group (mean difference in overall suffering score=-2.0, 95% CI=-2.7 to -1.4, t=-6.125, p=0.000) and the control group (mean difference in overall suffering score=-1.6, 95% CI=-2.3 to -0.8, t=-4.106, p=0.037). There were also significant improvements in the total Hospital Anxiety and Depression Scale score (mean difference=-3.4, 95% CI=-5.3 to -1.5, t=-3.525, p=0.000) and the total Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being score (mean difference=7.3, 95% CI=1.5 to 13.1, t=2.460, p=0.014) in the intervention group after 7 days, but not in the control group. Conclusion: The results provide evidence that 7 days of mindful gratitude journaling could positively affect the state of suffering, psychological distress and quality of life of patients with advanced cancer. Trial registration number: The trial was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN1261800172191) and conducted in accordance with the Declaration of Helsinki.

BMJ supportive & palliative care · randomised controlled trial · 17 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 →

Job strain as a risk factor for coronary heart disease: a collaborative meta-analysis of individual participant data.

Background: Published work assessing psychosocial stress (job strain) as a risk factor for coronary heart disease is inconsistent and subject to publication bias and reverse causation bias. We analysed the relation between job strain and coronary heart disease with a meta-analysis of published and unpublished studies. Methods: We used individual records from 13 European cohort studies (1985-2006) of men and women without coronary heart disease who were employed at time of baseline assessment. We measured job strain with questions from validated job-content and demand-control questionnaires. We extracted data in two stages such that acquisition and harmonisation of job strain measure and covariables occurred before linkage to records for coronary heart disease. We defined incident coronary heart disease as the first non-fatal myocardial infarction or coronary death. Findings: 30,214 (15%) of 197,473 participants reported job strain. In 1·49 million person-years at risk (mean follow-up 7·5 years [SD 1·7]), we recorded 2358 events of incident coronary heart disease. After adjustment for sex and age, the hazard ratio for job strain versus no job strain was 1·23 (95% CI 1·10-1·37). This effect estimate was higher in published (1·43, 1·15-1·77) than unpublished (1·16, 1·02-1·32) studies. Hazard ratios were likewise raised in analyses addressing reverse causality by exclusion of events of coronary heart disease that occurred in the first 3 years (1·31, 1·15-1·48) and 5 years (1·30, 1·13-1·50) of follow-up. We noted an association between job strain and coronary heart disease for sex, age groups, socioeconomic strata, and region, and after adjustments for socioeconomic status, and lifestyle and conventional risk factors. The population attributable risk for job strain was 3·4%. Interpretation: Our findings suggest that prevention of workplace stress might decrease disease incidence; however, this strategy would have a much smaller effect than would tackling of standard risk factors, such as smoking. Funding: Finnish Work Environment Fund, the Academy of Finland, the Swedish Research Council for Working Life and Social Research, the German Social Accident Insurance, the Danish National Research Centre for the Working Environment, the BUPA Foundation, the Ministry of Social Affairs and Employment, the Medical Research Council, the Wellcome Trust, and the US National Institutes of Health.

Lancet (London, England) · meta-analysis · 578 citationsread the source →

The reliability of relationship satisfaction: a reliability generalization meta-analysis.

We conducted a reliability-generalization meta-analysis of 7 of the most frequently used measures of relationship satisfaction: the Locke-Wallace Marital Adjustment Test (LWMAT), the Kansas Marital Satisfaction Scale (KMS), the Quality of Marriage Index, the Relationship Assessment Scale, the Marital Opinion Questionnaire, Karney and Bradbury's (1997) semantic differential scale, and the Couples Satisfaction Index. Six hundred thirty-nine reliability coefficients from 398 articles and 636,806 individuals provided internal consistency reliability estimates for this meta-analysis. We present the average score reliabilities for each measure, characterize the variance in score reliabilities across studies, and consider sample and study characteristics that are predictive of score reliability. Overall, the KMS and the LWMAT appear to be the strongest and weakest measures, respectively, from a reliability perspective. We discuss the importance of considering reliability invariance when making cross-group comparisons and provide recommendations for researchers when electing a measure of relationship satisfaction.

Journal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43) · meta-analysis · 64 citationsread the source →

Interventions for treating femoral shaft fractures in children and adolescents.

Background: Fractures of the femoral shaft in children are relatively uncommon but serious injuries that disrupt the lives of children and their carers and can result in significant long-term disability. Treatment involves either surgical fixation, such as intramedullary nailing or external fixation, or conservative treatment involving prolonged immobilisation, often in hospital. Objectives: To assess the effects (benefits and harms) of interventions for treating femoral shaft fractures in children and adolescents. Search methods: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (accessed 16 August 2013), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2013 Issue 7), MEDLINE (1946 to August Week 1 2013), EMBASE (1980 to 2012 week 9), CINAHL (16 August 2013), clinical trials registries, conference proceedings and reference lists; and contacted trial authors and experts in the field. Selection criteria: Randomised and quasi-randomised controlled trials comparing conservative and surgical interventions for diaphyseal fractures of the femur in children under 18 years of age. Our primary outcomes were functional outcome measures, unacceptable malunion, and serious adverse events. Data collection and analysis: Two authors independently screened and selected trials, assessed risk of bias and extracted data. We assessed the overall quality of the evidence for each outcome for each comparison using the GRADE approach. We pooled data using a fixed-effect model. Main results: We included 10 trials (six randomised and four quasi-randomised) involving a total of 527 children (531 fractures). All trials were at some risk of bias, including performance bias as care provider blinding was not practical, but to a differing extent. Just one trial was at low risk of selection bias. Reflecting both the risk of bias and the imprecision of findings, we judged the quality of evidence to be 'low' for most outcomes, meaning that we are unsure about the estimates of effect. Most trials failed to report on self-assessed function or when children resumed their usual activities. The trials evaluated 10 different comparisons, belonging to three main categories. Surgical versus conservative treatment Four trials presenting data for 264 children aged 4 to 12 years made this comparison. Low quality evidence (one trial, 101 children) showed children had very similar function assessed using the RAND health status score at two years after surgery (external fixation) compared with conservative treatment (spica cast): mean 69 versus 68. The other three trials did not report on function. There was moderate quality evidence (four trials, 264 children, aged 4 to 12 years, followed up 3 to 24 months) that surgery reduced the risk of malunion (risk ratio (RR) 0.29, 95% confidence interval (CI) 0.15 to 0.59, 4 trials). Assuming an illustrative baseline risk of 115 malunions per 1000 in children treated conservatively, these data equate to 81 fewer (95% CI 47 to 97 fewer) malunions per 1000 in surgically-treated children. Conversely, low quality evidence indicated that there were more serious adverse events such as infections after surgery (RR 2.39, 95% CI 1.10 to 5.17, 4 trials). Assuming an illustrative baseline risk of 40 serious adverse events per 1000 for conservative treatment, these data equate to 56 more (95% CI 4 to 167 more) serious adverse events per 1000 children treated surgically. There was low quality evidence (one trial, 101 children) of similar satisfaction levels in children and parents with surgery involving external fixation and plaster cast only. However, there was low quality evidence (one trial, 46 children) that more parents were satisfied with intramedullary nailing than with traction followed by a cast, and that surgery reduced the time taken off from school. Comparisons of different methods of conservative treatmentThe three trials in this category made three different comparisons. We are very unsure if unacceptable malunion rates differ between immediate hip spica versus skeletal traction followed by spica in children aged 3 to 10 years followed up for six to eight weeks (RR 4.0, 95% CI 0.5 to 32.9; one trial, 42 children; very low quality evidence). Malunion rates at 5 to 10 years may not differ between traction followed by functional orthosis versus traction followed by spica cast in children aged 5 to 13 years (RR 0.98, 95% CI 0.46 to 2.12; one trial, 43 children; low quality evidence). We are very unsure (very low quality evidence) if either function or serious adverse events (zero events reported) differ between single-leg versus double-leg spica casts (one trial, 52 young children aged two to seven years). Low quality evidence on the same comparison indicates that single-leg casts are less awkward to manage by parents, more comfortable for the child and may require less time off work by the caregiver. Comparisons of different methods of surgical treatmentThe three trials in this category made three different comparisons. Very low quality evidence means that we are very unsure if the rates of malunion, serious adverse events, time to return to school or parental satisfaction actually differ in children whose fractures were fixed using elastic stable intramedullary nailing or external fixation (one trial, 19 children). The same applies to the rates of serious adverse events and time to resume full weight-bearing in children treated with dynamic versus static external fixation (one trial, 52 children). Very low quality evidence (one trial, 47 children) means that we do not know if malunion, serious adverse events and time to resume weight-bearing actually differ between intramedullary nailing versus submuscular plating. However, there could be more difficulties in plate removal subsequently. Authors' conclusions: There is insufficient evidence to determine if long-term function differs between surgical and conservative treatment. Surgery results in lower rates of malunion in children aged 4 to 12 years, but may increase the risk of serious adverse events. Elastic stable intramedullary nailing may reduce recovery time. There is insufficient evidence from comparisons of different methods of conservative treatment or of different methods of surgical treatment to draw conclusions on the relative effects of the treatments compared in the included trials.

The Cochrane database of systematic reviews · meta-analysis · 23 citationsread the source →

The Social Epidemiology of Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome

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

Association of Early-Life Antibiotic Use and Protective Effects of Breastfeeding: Role of the Intestinal Microbiota.

Importance: Long duration of breastfeeding is known to reduce the frequency of infections and the risk of overweight, both of which are prevalent health problems among children, but the mechanisms are unclear. Objectives: To test whether early-life antibiotic use in children prevents the beneficial long-term effects of breastfeeding on weight development and lifetime antibiotic use, and to investigate whether the duration of breastfeeding is associated with long-term microbiota development. Design, setting, and participants: Retrospective cohort study, conducted from June 2015 to December 2015, of the association between the duration of breastfeeding and lifetime antibiotic use by children as well as body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) z score in a cohort of 226 healthy children aged 2 to 6 years attending day care at the study area in northern Finland and participating in a probiotic trial from October 1, 2009, through April 30, 2010. Fecal microbiota composition analysis was performed in a subcohort of 42 of these children. Exposures: Duration of breastfeeding and the number of different antibiotic courses purchased for the child. Main outcomes and measures: The BMI z score, lifetime antibiotic use after weaning, and fecal microbiota composition. Results: A total of 226 children (mean [SD] age, 55 [1.4] months; 54% male) were included in the study. Among the 113 children with no antibiotics before weaning, each month of breastfeeding decreased the mean number of postweaning antibiotic courses by 5% (95% CI, 2% to 8%; P = .001) and mean BMI z scores by 0.08 unit (95% CI, 0.04 to 0.11; P < .001). Among the 113 early-life antibiotic users, the effect of breastfeeding on postweaning antibiotic use was borderline significant (estimated 4% decrease per month; 95% CI, 0% to 7%; P = .04) and the effect on BMI z score disappeared (estimated 1% increase; 95% CI, -3% to 5%; P = .50). In the subcohort of 42 children with fecal microbiota composition analysis, the children with short breastfeeding duration (0-6 months) and no early-life antibiotic use or with long breastfeeding duration (8-16 months) and early-life use of antibiotics had a significantly lower abundance of Bifidobacterium (by 55%; 95% CI, 43% to 87%; P = .006; and 39%, 95% CI, 30% to 68%; P < .001, respectively) and Akkermansia (by 71%; 95% CI, 28% to 87%; P = .008; and 69%; 95% CI, 22% to 90%; P = .02, respectively) compared with those with long duration of breastfeeding and no early-life antibiotics. Conclusions and relevance: Antibiotic use in a child during breastfeeding may weaken the beneficial effects of long breastfeeding duration. The results suggest that particularly the long-term metabolic benefits of breastfeeding are conveyed by the intestinal microbiota.

JAMA pediatrics · clinical trial · 75 citationsread the source →

Exercise on prescription for women aged 40-74 recruited through primary care: two year randomised controlled trial.

Objective: To assess the effectiveness of a primary care based programme of exercise on prescription among relatively inactive women over a two year period. Design: Randomised controlled trial. Setting: 17 primary care practices in Wellington, New Zealand Participants: 1089 women aged 40-74 not undertaking 30 minutes of moderate intensity physical activity on at least five days of the week Intervention: Brief physical activity intervention led by nurse with six month follow-up visit and monthly telephone support over nine months. Main outcome measure: Physical activity assessed at baseline and 12 and 24 months. Secondary outcomes were quality of life (SF-36), weight, waist circumference, blood pressure, concentrations of fasting serum lipids, glycated haemoglobin (HbA(1c)), glucose, insulin, and physical fitness. Results: Mean age was 58.9 (SD 7) years. Trial retention rates were 93% and 89% at 12 and 24 months, respectively. At baseline, 10% of intervention participants and 11% of control participants were achieving 150 minutes of at least moderate intensity physical activity a week. At 12 months rates increased to 43% and 30% and at 24 months to 39.3% and 32.8% (P<0.001), respectively. SF-36 physical functioning (P=0.03) and mental health (P<0.05) scores improved more in intervention compared with control participants, but role physical scores were significantly lower (P<0.01). There were no significant differences in clinical outcomes. More falls (P<0.001) and injuries (P=0.03) were recorded in the intervention group. Conclusions: This programme of exercise on prescription increased physical activity and quality of life over two years, although falls and injuries also increased. This finding supports the use of exercise on prescription programmes as part of population strategies to reduce physical inactivity. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ANZCTRN012605000490673.

BMJ (Clinical research ed.) · randomised controlled trial · 108 citationsread the source →

Long-term quality-of-life outcomes after radical prostatectomy or watchful waiting: the Scandinavian Prostate Cancer Group-4 randomised trial.

Background: For men with localised prostate cancer, surgery provides a survival benefit compared with watchful waiting. Treatments are associated with morbidity. Results for functional outcome and quality of life are rarely reported beyond 10 years and are lacking from randomised settings. We report results for quality of life for men in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) after a median follow-up of more than 12 years. Methods: All living Swedish and Finnish men (400 of 695) randomly assigned to radical prostatectomy or watchful waiting in SPCG-4 from 1989 to 1999 were included in our analysis. An additional 281 men were included in a population-based control group matched for region and age. Physical symptoms, symptom-induced stress, and self-assessed quality of life were evaluated with a study-specific questionnaire. Longitudinal data were available for 166 Swedish men who had answered quality-of-life questionnaires at an earlier timepoint. Findings: 182 (88%) of 208 men in the radical prostatectomy group, 167 (87%) of 192 men in the watchful-waiting group, and 214 (76%) of 281 men in the population-based control group answered the questionnaire. Men in SPCG-4 had a median follow-up of 12·2 years (range 7-17) and a median age of 77·0 years (range 61-88). High self-assessed quality of life was reported by 62 (35%) of 179 men allocated radical prostatectomy, 55 (34%) of 160 men assigned to watchful waiting, and 93 (45%) of 208 men in the control group. Anxiety was higher in the SPCG-4 groups (77 [43%] of 178 and 69 [43%] of 161 men) than in the control group (68 [33%] of 208 men; relative risk 1·42, 95% CI 1·07-1·88). Prevalence of erectile dysfunction was 84% (146 of 173 men) in the radical prostatectomy group, 80% (122 of 153) in the watchful-waiting group, and 46% (95 of 208) in the control group and prevalence of urinary leakage was 41% (71 of 173), 11% (18 of 164), and 3% (six of 209), respectively. Distress caused by these symptoms was reported significantly more often by men allocated radical prostatectomy than by men assigned to watchful waiting. In a longitudinal analysis of men in SPCG-4 who provided information at two follow-up points 9 years apart, 38 (45%) of 85 men allocated radical prostatectomy and 48 (60%) of 80 men allocated watchful waiting reported an increase in number of physical symptoms; 50 (61%) of 82 and 47 (64%) of 74 men, respectively, reported a reduction in quality of life. Interpretation: For men in SPCG-4, negative side-effects were common and added more stress than was reported in the control population. In the radical prostatectomy group, erectile dysfunction and urinary leakage were often consequences of surgery. In the watchful-waiting group, side-effects can be caused by tumour progression. The number and severity of side-effects changes over time at a higher rate than is caused by normal ageing and a loss of sexual ability is a persistent psychological problem for both interventions. An understanding of the patterns of side-effects and time dimension of their occurrence for each treatment is important for full patient information. Funding: US National Institutes of Health; Swedish Cancer Society; Foundation in Memory of Johanna Hagstrand and Sigfrid Linnér.

The Lancet. Oncology · randomised controlled trial · 277 citationsread the source →

Nicotine therapy sampling to induce quit attempts among smokers unmotivated to quit: a randomized clinical trial.

Background: Rates of smoking cessation have not changed in a decade, accentuating the need for novel approaches to prompt quit attempts. Methods: Within a nationwide randomized clinical trial (N = 849) to induce further quit attempts and cessation, smokers currently unmotivated to quit were randomized to a practice quit attempt (PQA) alone or to nicotine replacement therapy (hereafter referred to as nicotine therapy), sampling within the context of a PQA. Following a 6-week intervention period, participants were followed up for 6 months to assess outcomes. The PQA intervention was designed to increase motivation, confidence, and coping skills. The combination of a PQA plus nicotine therapy sampling added samples of nicotine lozenges to enhance attitudes toward pharmacotherapy and to promote the use of additional cessation resources. Primary outcomes included the incidence of any ever occurring self-defined quit attempt and 24-hour quit attempt. Secondary measures included 7-day point prevalence abstinence at any time during the study (ie, floating abstinence) and at the final follow-up assessment. Results: Compared with PQA intervention, nicotine therapy sampling was associated with a significantly higher incidence of any quit attempt (49% vs 40%; relative risk [RR], 1.2; 95% CI, 1.1-1.4) and any 24-hour quit attempt (43% vs 34%; 1.3; 1.1-1.5). Nicotine therapy sampling was marginally more likely to promote floating abstinence (19% vs 15%; RR, 1.3; 95% CI, 1.0-1.7); 6-month point prevalence abstinence rates were no different between groups (16% vs 14%; 1.2; 0.9-1.6). Conclusion: Nicotine therapy sampling during a PQA represents a novel strategy to motivate smokers to make a quit attempt. Trial registration: clinicaltrials.gov Identifier: NCT00706979.

Archives of internal medicine · randomised controlled trial · 109 citationsread the source →

A double-blind, randomized clinical trial comparing soybean oil-based versus olive oil-based lipid emulsions in adult medical-surgical intensive care unit patients requiring parenteral nutrition.

Objective: Parenteral nutrition has been associated with metabolic and infectious complications in intensive care unit patients. The underlying mechanism for the high risk of complications is not known but may relate to the proinflammatory effects of soybean oil-based lipid emulsions, the only Food and Drug Administration-approved lipid formulation for clinical use. Design: Prospective, double-blind, randomized, controlled trial. Setting: Medical-surgical intensive care units from a major urban teaching hospital and a tertiary referral university hospital. Patients: Adult medical-surgical intensive care unit patients. Intervention: Parenteral nutrition containing soybean oil-based (Intralipid) or olive oil-based (ClinOleic) lipid emulsions. Measurements: Differences in hospital clinical outcomes (nosocomial infections and noninfectious complications), hospital length of stay, glycemic control, inflammatory and oxidative stress markers, and granulocyte and monocyte functions between study groups. Results: A total of 100 patients were randomized to either soybean oil-based parenteral nutrition or olive oil-based parenteral nutrition for up to 28 days. A total of 49 patients received soybean oil-based parenteral nutrition (age 51 ± 15 yrs, body mass index 27 ± 6 kg/m2, and Acute Physiology and Chronic Health Evaluation II score 15.5 ± 7 [±SD]), and a total of 51 patients received olive oil-based lipid emulsion in parenteral nutrition (age 46 ± 19 yrs, body mass index 27 ± 8 kg/m2, and Acute Physiology and Chronic Health Evaluation II score 15.1 ± 6 [±SD]) for a mean duration of 12.9 ± 8 days. The mean hospital blood glucose concentration during parenteral nutrition was 129 ± 14 mg/dL, without differences between groups. Patients treated with soybean oil-based and olive oil-based parenteral nutrition had a similar length of stay (47 ± 47 days and 41 ± 36 days, p = .49), mortality (16.3% and 9.8%, p = .38), nosocomial infections (43% vs. 57%, p = .16), and acute renal failure (26% vs. 18%, p = .34). In addition, there were no differences in inflammatory and oxidative stress markers or in granulocyte and monocyte functions between groups. Conclusion: The administration of parenteral nutrition containing soybean oil-based and olive oil-based lipid emulsion resulted in similar rates of infectious and noninfectious complications and no differences in glycemic control, inflammatory and oxidative stress markers, and immune function in critically ill adults.

Critical care medicine · randomised controlled trial · 43 citationsread the source →

Breaking bad news education for emergency medicine residents: A novel training module using simulation with the SPIKES protocol.

Breaking bad news (BBN) in the emergency department (ED) is a common occurrence. This is especially true for an emergency physician (EP) as there is little time to prepare for the event and likely little or no knowledge of the patients or family background information. At our institution, there is no formal training for EP residents in delivering bad news. We felt teaching emergency medicine residents these communication skills should be an important part of their educational curriculum. We describe our experience with a defined educational program designed to educate and improve physician's confidence and competence in bad news and death notification. A regularly scheduled 5-h grand rounds conference time frame was dedicated to the education of EM residents about BBN. A multidisciplinary approach was taken to broaden the prospective of the participants. The course included lectures from different specialties, role playing for three short scenarios in different capacities, and hi-fidelity simulation cases with volatile psychosocial issues and stressors. Participants were asked to fill out a self-efficacy form and evaluation sheets. Fourteen emergency residents participated and all thought that this education is necessary. The mean score of usefulness is 4.73 on a Likert Scale from 1 to 5. The simulation part was thought to be the most useful (43%), with role play 14%, and lecture 7%. We believe that teaching physicians to BBN in a controlled environment is a good use of educational time and an important procedure that EP must learn.

Journal of emergencies, trauma, and shock · 62 citationsread the source →

Prevalence of and Factors Related to Discordance About Prognosis Between Physicians and Surrogate Decision Makers of Critically Ill Patients.

Importance: Misperceptions about prognosis by individuals making decisions for incapacitated critically ill patients (surrogates) are common and often attributed to poor comprehension of medical information. Objective: To determine the prevalence of and factors related to physician-surrogate discordance about prognosis in intensive care units (ICUs). Design, setting, and participants: Mixed-methods study comprising quantitative surveys and qualitative interviews conducted in 4 ICUs at a major US medical center involving surrogate decision makers and physicians caring for patients at high risk of death from January 4, 2005, to July 10, 2009. Main outcomes and measures: Discordance about prognosis, defined as a difference between a physician's and a surrogate's prognostic estimates of at least 20%; misunderstandings by surrogates (defined as any difference between a physician's prognostic estimate and a surrogate's best guess of that estimate); differences in belief (any difference between a surrogate's actual estimate and their best guess of the physician's estimate). Results: Two hundred twenty-nine surrogate decision makers (median age, 47 [interquartile range {IQR}, 35-56] years; 68% women) and 99 physicians were involved in the care of 174 critically ill patients (median age, 60 [IQR, 47-74] years; 44% women). Physician-surrogate discordance about prognosis occurred in 122 of 229 instances (53%; 95% CI, 46.8%-59.7%). In 65 instances (28%), discordance was related to both misunderstandings by surrogates and differences in belief about the patient's prognosis; 38 (17%) were related to misunderstandings by surrogates only; 7 (3%) were related to differences in belief only; and data were missing for 12. Seventy-five patients (43%) died. Surrogates' prognostic estimates were much more accurate than chance alone, but physicians' prognostic estimates were statistically significantly more accurate than surrogates' (C statistic, 0.83 vs 0.74; absolute difference, 0.094; 95% CI, 0.024-0.163; P = .008). Among 71 surrogates interviewed who had beliefs about the prognosis that were more optimistic than that of the physician, the most common reasons for optimism were a need to maintain hope to benefit the patient (n = 34), a belief that the patient had unique strengths unknown to the physician (n = 24), and religious belief (n = 19). Conclusions and relevance: Among critically ill patients, discordant expectations about prognosis were common between patients' physicians and surrogate decision makers and were related to misunderstandings by surrogates about physicians' assessments of patients' prognoses and differences in beliefs about patients' prognoses.

JAMA · cohort or longitudinal · 151 citationsread the source →

Joblessness and Lost Earnings after Acute Respiratory Distress Syndrome in a 1-Year National Multicenter Study.

Rationale: Following acute respiratory distress syndrome (ARDS), joblessness is common but poorly understood. Objectives: To evaluate the timing of return to work after ARDS, and associated risk factors, lost earnings, and changes in healthcare coverage Methods: Over 12-month longitudinal follow-up, ARDS survivors from 43 U.S. ARDSNet hospitals provided employment and healthcare coverage data via structured telephone interviews. Factors associated with the timing of return to work were assessed using Fine and Gray regression analysis. Lost earnings were estimated using Bureau of Labor Statistics data. Measurements and main results: Of 922 consenting survivors, 386 (42%) were employed before ARDS (56% male; mean ± SD age, 45 ± 13 yr), with seven dying by 12-month follow-up. Of 379 previously employed 12-month survivors, 166 (44%) were jobless at 12-month follow-up. Accounting for competing risks of death and retirement, half of enrolled and previously employed survivors returned to work by 13 weeks after hospital discharge, with 68% ever returning by 12 months. Delays in return to work were associated with longer hospitalization and older age among nonwhite survivors. Over 12-month follow-up, 274 (71%) survivors accrued lost earnings, averaging $26,949 ± $22,447 (60% of pre-ARDS annual earnings). Jobless survivors experienced a 14% (95% confidence interval, 5-22%; P = 0.002) absolute decrease in private health insurance (from 44% pre-ARDS) and a 16% (95% confidence interval, 7-24%; P < 0.001) absolute increase in Medicare and Medicaid (from 33%). Conclusions: At 12 months after ARDS, nearly one-half of previously employed survivors were jobless. Post-ARDS joblessness is associated with readily identifiable patient and hospital variables and accompanied by substantial lost earnings and a shift toward government-funded healthcare coverage.

American journal of respiratory and critical care medicine · cohort or longitudinal · 124 citationsread the source →

Testing the generalizability of couple communication typologies: A multisite replication and extension study.

Research on couple typologies has advanced our understanding of the communication patterns that distinguish happy from distressed partners. However, this work has suffered from a lack of conceptual and methodological cohesion and replication in large, heterogeneous samples, resulting in idiosyncratic typologies with limited generalizability beyond their initial development. The present study replicates and extends prior research by testing the external validity of previous communication typologies in a multisite sample of couples. We combined data from 13 studies that used the Rapid Marital Interaction Coding System to observe communication during mixed-gender couples' 10-min conflict interactions (N = 1,957). We used latent profile analysis to examine men's and women's (a) positive, negative, and neutral behavior and (b) positive and negative reciprocity. Groups were compared on relationship satisfaction and intimate partner violence to further characterize differences among couple subtypes. A five-class solution revealed couples whose communication can be described as (a) task-oriented (low positivity/negativity, high neutral problem discussion; 53%), (b) warm (high positivity/low negativity; 24%), (c) hostile (low positivity/high negativity; 9%), (d) expressive (high positivity/negativity; 7%), and (e) warm-but-reactive (high positivity/low negativity, high negative reciprocity; 6%). Men and women reported the highest levels of satisfaction in the warm, task-oriented, and warm-but-reactive groups. Intimate partner violence was highest in the hostile and expressive groups. These outcomes are largely concordant with the previous findings and should increase the field's confidence in the generalizability of earlier typologies. Our findings also raise new questions about the heterogeneous nature of communication among happy couples. We discuss these questions and their clinical implications. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Journal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43) · cohort or longitudinalread the source →

Healthy lifestyle and life expectancy at age 30 years in the Chinese population: an observational study.

Background: The improvement of life expectancy is one of the aims of the Healthy China 2030 blueprint. We aimed to investigate the extent to which healthy lifestyles are associated with life expectancy in Chinese adults. Methods: We used the prospective China Kadoorie Biobank (CKB) study to examine the relative risk of mortality associated with individual and combined lifestyle factors (never smoking or quitting not for illness, no excessive alcohol use, being physically active, healthy eating habits, and healthy body shape). Participants with coronary heart disease, stroke, cancer, or missing values for body-mass index were excluded. For analysis of chronic respiratory diseases, participants with chronic obstructive pulmonary disease or asthma were excluded. We estimated the national prevalence of lifestyle factors using data from the China Nutrition and Health Surveillance (CNHS; 2015) and derived mortality rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (2015). All three data sources were combined to estimate the life expectancy of individuals at age 30 years following different levels of lifestyle factors by using the life table method. The cause-specific decomposition of the life expectancy differences was analysed using Arriaga's method. Findings: After the exclusion of CKB participants with coronary heart disease, stroke, cancer, or missing BMI data at baseline, 487 209 were included in the primary analysis. Participants with COPD or asthma at baseline were additionally excluded for chronic respiratory disease-related analysis, leaving 451 233 participants with data available for analysis. Data from 171 127 adults aged 30-84 years from the CNHS 2015 were used to estimate the sex-specific and age-specific prevalence of lifestyle-related factors. There were 42 496 deaths documented over a median follow-up of 11·1 years (IQR 10·2-12·1) in CKB. The adjusted hazard ratios (aHRs) of participants adopting five versus 0-1 low-risk factors was 0·38 (95% CI 0·34-0·43) for all-cause mortality, aHR 0·37 (0·30-0·46) for cardiovascular disease mortality, aHR 0·47 (0·39-0·56) for cancer mortality, and aHR 0·30 (0·14-0·64) for chronic respiratory disease mortality. The life expectancy at age 30 years for individuals with 0-1 low-risk factors was on average 41·7 years (95% CI 41·5-42·0) for men and 47·3 years (46·6-48·0) for women. For individuals with all five low-risk factors, the life expectancy at age 30 was 50·5 years (95% CI 48·5-52·4) for men and 55·4 years (53·5-57·4) for women; meaning a difference of 8·8 years (95% CI 6·8-10·7) for men and 8·1 years (6·5-9·9) for women. The estimated extended life expectancy for men and women was mainly attributable to reduced death from cardiovascular disease (2·4 years [27% of the total extended life expectancy] for men and 3·7 years [46%] for women), cancer (2·6 years [30%] for men and 0·9 years [11%] for women), and chronic respiratory disease (0·6 years [7%] for men and 1·2 years [15%] for women). Interpretation: Our findings suggest that increasing the adoption of these five healthy lifestyle factors through public health interventions could be associated with substantial gains in life expectancy in the Chinese population. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Kadoorie Charitable Foundation, UK Wellcome Trust.

The Lancet. Public health · cohort or longitudinal · 129 citationsread the source →

Natural recovery and treatment-seeking in pathological gambling: results of two U.S. national surveys.

Objective: Pathological gambling is described in DSM-IV as a chronic and persisting disorder, but recent community-based longitudinal studies that have highlighted the transitory nature of gambling-related problems have called into question whether this is an accurate characterization. This emerging evidence of high rates of recovery coupled with low rates of treatment-seeking for pathological gambling suggests that natural recovery might be common. The purpose of the present study was to document the rates of recovery, treatment-seeking, and natural recovery among individuals with DSM-IV pathological gambling disorder in two large and representative U.S. national surveys. Method: Prevalences of recovery, treatment-seeking, and natural recovery were estimated among individuals from the Gambling Impact and Behavior Study (N=2,417) and the National Epidemiologic Survey on Alcohol and Related Conditions (N=43,093) who reported a lifetime history of DSM-IV pathological gambling disorder (N=21 and N=185, respectively). Results: Among individuals with a lifetime history of DSM-IV pathological gambling, 36%-39% did not experience any gambling-related problems in the past year, even though only 7%-12% had ever sought either formal treatment or attended meetings of Gamblers Anonymous. About one-third of the individuals with pathological gambling disorder in these two nationally representative U.S. samples were characterized by natural recovery. Conclusions: Pathological gambling may not always follow a chronic and persisting course. A substantial portion of individuals with a history of pathological gambling eventually recover, most without formal treatment. The results of large epidemiological surveys of pathological gambling may eventually overturn the established wisdom about pathological gambling disorder.

The American journal of psychiatry · cohort or longitudinal · 245 citationsread the source →

Transdiagnostic Symptom Clusters and Associations With Brain, Behavior, and Daily Function in Mood, Anxiety, and Trauma Disorders.

Importance: The symptoms that define mood, anxiety, and trauma disorders are highly overlapping across disorders and heterogeneous within disorders. It is unknown whether coherent subtypes exist that span multiple diagnoses and are expressed functionally (in underlying cognition and brain function) and clinically (in daily function). The identification of cohesive subtypes would help disentangle the symptom overlap in our current diagnoses and serve as a tool for tailoring treatment choices. Objective: To propose and demonstrate 1 approach for identifying subtypes within a transdiagnostic sample. Design, setting, and participants: This cross-sectional study analyzed data from the Brain Research and Integrative Neuroscience Network Foundation Database that had been collected at the University of Sydney and University of Adelaide between 2006 and 2010 and replicated at Stanford University between 2013 and 2017. The study included 420 individuals with a primary diagnosis of major depressive disorder (n = 100), panic disorder (n = 53), posttraumatic stress disorder (n = 47), or no disorder (healthy control participants) (n = 220). Data were analyzed between October 2016 and October 2017. Main outcomes and measures: We followed a data-driven approach to achieve the primary study outcome of identifying transdiagnostic subtypes. First, machine learning with a hierarchical clustering algorithm was implemented to classify participants based on self-reported negative mood, anxiety, and stress symptoms. Second, the robustness and generalizability of the subtypes were tested in an independent sample. Third, we assessed whether symptom subtypes were expressed at behavioral and physiological levels of functioning. Fourth, we evaluated the clinically meaningful differences in functional capacity of the subtypes. Findings were interpreted relative to a complementary diagnostic frame of reference. Results: Four hundred twenty participants with a mean (SD) age of 39.8 (14.1) years were included in the final analysis; 256 (61.0%) were female. We identified 6 distinct subtypes characterized by tension (n=81; 19%), anxious arousal (n=55; 13%), general anxiety (n=38; 9%), anhedonia (n=29; 7%), melancholia (n=37; 9%), and normative mood (n=180; 43%), and these subtypes were replicated in an independent sample. Subtypes were expressed through differences in cognitive control (F5,383 = 5.13, P < .001, ηp2 = 0.063), working memory (F5,401 = 3.29, P = .006, ηp2 = 0.039), electroencephalography-recorded β power in a resting paradigm (F5,357 = 3.84, P = .002, ηp2 = 0.051), electroencephalography-recorded β power in an emotional paradigm (F5,365 = 3.56, P = .004, ηp2 = 0.047), social functional capacity (F5,414 = 21.33, P < .001, ηp2 = 0.205), and emotional resilience (F5,376 = 15.10, P < .001, ηp2 = 0.171). Conclusions and relevance: These findings offer a data-driven framework for identifying robust subtypes that signify specific, coherent, meaningful associations between symptoms, behavior, brain function, and observable real-world function, and that cut across DSM-IV-defined diagnoses of major depressive disorder, panic disorder, and posttraumatic stress disorder.

JAMA psychiatry · 115 citationsread the source →

A critical reappraisal of current staging of Lewy-related pathology in human brain.

Sporadic Parkinson disease (sPD) or brainstem-predominant type of Lewy body (LB) disease, and dementia with Lewy bodies (DLB), the two most frequent alpha-synucleinopathies, are progressive multisystem neurodegenerative disorders with widespread occurrence of alpha-synuclein (AS) deposits in the central, peripheral, and autonomic nervous system. For both LB-related disorders, staging/classification systems based on semiquantitative assessment of the distribution and progression pattern of Lewy-related/AS pathology are used that are considered to be linked to clinical dysfunctions. In PD, a six-stage system (Braak) has been suggested to indicate a predictable sequence of lesions with ascending progression from medullary and olfactory nuclei to the cortex, the first two presymptomatic stages being related to incidental LB disease, stages 3 and 4 with motor symptoms, and the last two (cortical) stages may be frequently associated with cognitive impairment. DLB, according to consensus pathologic guidelines, by semiquantitative scoring of AS pathology (LB density and distribution) in specific brain regions, is distinguished into three phenotypes (brainstem, transitional/limbic, and diffuse neocortical), also considering concomitant Alzheimer-related pathology. Retrospective clinico-pathologic studies, although largely confirming the staging system, particularly for younger onset PD with long duration, have shown that between 6.3 and 43% of the cases did not follow the proposed caudo-rostral progression pattern of AS pathology. There was sparing of medullary nuclei in 7-8.3% of clinically manifested PD cases with AS inclusions in midbrain and cortex corresponding to Braak stages 4 and 5, whereas mild parkinsonian symptoms were already observed in stages 2 and 3. There is considerable clinical and pathologic overlap between PD (with or without dementia) and DLB, corresponding to Braak LB stages 5 and 6, both frequently associated with variable Alzheimer-type pathology. Dementia often does not correlate with progressed stages of LB pathology, but may also be related to concomitant Alzheimer lesions or mixed pathologies. There is no relationship between Braak LB stage and the clinical severity of PD, and the predictive validity of this concept is doubtful, since large unselected, retrospective autopsy series in 30-55% of elderly subjects with widespread AS/Lewy-related pathology (Braak stages 5 and 6) reported no definite neuropsychiatric symptoms, suggesting considerable cerebral compensatory mechanisms. Applying the original criteria to large dementia samples, 49% of positive cases were not classifiable. Therefore, modified criteria for the categorization of Lewy-related pathology were proposed for patients with a history of dementia. The causes and molecular basis of the not infrequent deviations from the current staging schemes of AS pathology in PD and DLB, its relation to the onset of classical parkinsonian symptoms and for the lack of definite clinical deficits despite widespread AS pathology in the nervous system remain to be elucidated.

Acta neuropathologica · review · 158 citationsread the source →

Essential Hypertension

HomeCirculationVol. 101, No. 3Essential Hypertension Free AccessOtherPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessOtherPDF/EPUBEssential Hypertension Part I: Definition and Etiology Oscar A. Carretero and Suzanne Oparil Oscar A. CarreteroOscar A. Carretero From the Hypertension and Vascular Research Division, Heart and Vascular Institute, Henry Ford Hospital, Detroit, Mich (O.A.C.), and the Division of Cardiovascular Disease, Vascular Biology and Hypertension Program, University of Alabama School of Medicine, Birmingham (S.O.). and Suzanne OparilSuzanne Oparil From the Hypertension and Vascular Research Division, Heart and Vascular Institute, Henry Ford Hospital, Detroit, Mich (O.A.C.), and the Division of Cardiovascular Disease, Vascular Biology and Hypertension Program, University of Alabama School of Medicine, Birmingham (S.O.). Originally published25 Jan 2000https://doi.org/10.1161/01.CIR.101.3.329Circulation. 2000;101:329–335Essential hypertension remains a major modifiable risk factor for cardiovascular disease (CVD) despite important advances in our understanding of its pathophysiology and the availability of effective treatment strategies. High blood pressure (BP) increases the risk of CVD for millions of people worldwide, and there is evidence that the problem is only getting worse. In the past decade, age-adjusted rates of stroke incidence have risen, and the slope of the age-adjusted rate of decline in coronary disease has leveled off. The incidence of end-stage renal disease and the prevalence of heart failure have also increased. A major contributor to these trends is inadequate control of BP in the hypertensive population. This review of current concepts regarding the definition, etiology, and treatment of essential hypertension is intended to aid the clinician in identifying those individuals at high risk who need to undergo evaluation and treatment, as well as in selecting optimal treatment strategies for hypertensive patients with comorbid conditions and/or target organ damage. The part of the review that deals with the genetic basis of hypertension and the gene/environment interaction that may lead to elevated BP is still a work in progress. Information gained from the Human Genome Project and from ongoing studies of the genetic basis of hypertension both in animal models and human populations may revolutionize the treatment of hypertension by replacing current empirical therapy with more effective, targeted treatments based on the genotype of the patient. Concepts introduced in this review form the basis for such "pharmacogenomic" approaches to antihypertensive therapy. Definition of Essential or Primary HypertensionBP is a quantitative trait that is highly variable1 ; in population studies, BP has a normal distribution that is slightly skewed to the right. There is a strong positive and continuous correlation between BP and the risk of CVD (stroke, myocardial infarction, heart failure), renal disease, and mortality, even in the normotensive range. This correlation is more robust with systolic than with diastolic BP.2 There is no specific level of BP where cardiovascular and renal complications start to occur; thus the definition of hypertension is arbitrary but needed for practical reasons in patient assessment and treatment. The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) defined and classified hypertension in adults, as shown in Table 1.3 The diagnosis of hypertension is made when the average of 2 or more diastolic BP measurements on at least 2 subsequent visits is ≥90 mm Hg or when the average of multiple systolic BP readings on 2 or more subsequent visits is consistently ≥140 mm Hg. Isolated systolic hypertension is defined as systolic BP ≥140 mm Hg and diastolic BP <90 mm Hg. Individuals with high normal BP tend to maintain pressures that are above average for the general population and are at greater risk for development of definite hypertension and cardiovascular events than the general population. With the use of these definitions, it is estimated that 43 million people in the United States have hypertension or are taking antihypertensive medication, which is ≈24% of the adult population. This proportion changes with (1) race, being higher in blacks (32.4%) and lower in whites (23.3%) and Mexican Americans (22.6%); (2) age, because in industrialized countries systolic BP rises throughout life, whereas diastolic BP rises until age 55 to 60 years and thus the greater increase in prevalence of hypertension among the elderly is mainly due to systolic hypertension; (3) geographic patterns, because hypertension is more prevalent in the southeastern United States; (4) gender, because hypertension is more prevalent in men (though menopause tends to abolish this difference); and (5) socioeconomic status, which is an indicator of lifestyle attributes and is inversely related to the prevalence, morbidity, and mortality rates of hypertension. Essential, primary, or idiopathic hypertension is defined as high BP in which secondary causes such as renovascular disease, renal failure, pheochromocytoma, aldosteronism, or other causes of secondary hypertension or mendelian forms (monogenic) are not present. Essential hypertension accounts for 95% of all cases of hypertension. Essential hypertension is a heterogeneous disorder, with different patients having different causal factors that lead to high BP. Essential hypertension needs to be separated into various syndromes because the causes of high BP in most patients presently classified as having essential hypertension can be recognized. Known Etiological Factors in Essential HypertensionAlthough it has frequently been indicated that the causes of essential hypertension are not known, this is only partially true because we have little information on genetic variations or genes that are overexpressed or underexpressed as well as the intermediary phenotypes that they regulate to cause high BP.4 A number of factors increase BP, including (1) obesity, (2) insulin resistance, (3) high alcohol intake, (4) high salt intake (in salt-sensitive patients), (5) aging and perhaps (6) sedentary lifestyle, (7) stress, (8) low potassium intake, and (9) low calcium intake.56 Furthermore, many of these factors are additive, such as obesity and alcohol intake. In this review, variations in BP that are genetically determined will be called "inherited BP," although we do not know which genes cause BP to vary; we know from family studies that inherited BP can range from low normal BP to severe hypertension. Factors that increase BP, such as obesity and high alcohol and salt intake, will be called "hyperten-sinogenic factors." Some of these factors have inherited, behavioral, and environmental components. Inherited BP could be considered core BP, whereas hypertensinogenic factors cause BP to increase above the range of inherited BPs, thus creating 4 main possibilities: (1) patients who have inherited BP in the optimal category (<120/<80 mm Hg); if 1 or more hypertensinogenic factors are added, BP would probably increase but remain in the normal range (<135/<85 mm Hg) (Figure 1, first 2 columns); (2) patients who have inherited BP in the normal category (≤130/≤85 mm Hg); if 1 or more hypertensinogenic factors are added, BP will probably increase to the high normal range (130 to 139/85 to 89 mm Hg) or to stage 1 of the hypertensive category (140 to 159/90 to 99 mm Hg) (Figure 1, second 2 columns); (3) patients who have inherited BP in the high normal category (130 to 139/85 to 89 mm Hg); if 1 or more hypertensinogenic factors are added, BP will increase to the hypertensive range (≥140/≥90 mm Hg) (Figure 1, third 2 columns); and (4) patients who have inherited BP in the hypertensive range; addition of 1 or more hypertensinogenic factors will make hypertension more severe, changing it from stage 1 to stage 2 or 3 (Figure 1, fourth to sixth 2 columns).Theoretically, in a population unaffected by hypertensinogenic factors, BP will have a normal distribution; it will be skewed to the right and will have a narrow base or less variance (Figure 2, continuous line). When 1 hypertensinogenic factor is added to this population, such as increased body mass, one would expect the normal distribution curve to be further skewed to the right; consequently the base will be wider (more variance) and the curve will be flatter (Figure 2, broken line). If a second hypertensinogenic factor such as alcohol intake is added to increased body mass, the curve will be skewed more to the right and the variance will increase further, with more subjects classified as hypertensive (Figure 2, dotted line).Discovering which genetic variations place BP on the left or right side of the distribution curve is of both theoretical and practical importance because it could help the physician to better treat or cure hypertension.7 Recognition of the hypertensinogenic factors may allow nonpharmacological prevention, treatment, or cure of hypertension. Hypertensinogenic factors such as obesity, insulin resistance, or high alcohol intake also have an important genetic component. Furthermore, there are interactions between genetic and environmental factors (Figure 2) that influence intermediary phenotypes such as sympathetic nerve activity, the renin-angiotensin-aldosterone and renal kallikrein-kinin systems, and endothelial factors, which in turn influence other intermediary phenotypes such as sodium excretion, vascular reactivity, and cardiac contractility. These and many other intermediary phenotypes determine total vascular resistance and cardiac output and, consequently, BP. Recognition of the hypertensinogenic factor(s) and establishing that the patient's hypertension is the result of obesity (either alone or combined with other factors such as insulin resistance or high alcohol intake) or old age instead of essential hypertension may help the physician as well as the patient and his or her family to modify or eliminate these hypertensinogenic and CVD risk factors when possible, which may cure the hypertension or at least facilitate control of BP. When the hypertensinogenic factor cannot be reduced or eliminated, as with systolic hypertension induced by aging (arteriosclerosis), recognition of the underlying cause of high BP will emphasize the need for (1) further studies to determine whether the patient has arteriosclerosis and/or atherosclerosis, the magnitude of the disease, and whether there are occlusive lesions; (2) treatment of the atherosclerosis with lifestyle and dietary changes and lipid-lowering agents if necessary; and (3) pharmacological treatment of systolic hypertension to decrease passive stiffness (arteriosclerosis) of the major central elastic arteries and decrease morbidity and mortality rates. Thus recognition of factors that induce hypertension is not only of theoretical but also of practical importance. In conclusion, as stated by Beilin,8 "it is no longer appropriate to define essential hypertension as a rise in blood pressure without cause," since a number of causes can be clearly identified in most cases of so-called "essential hypertension." As discussed later in more detail, there is clear evidence that changes in lifestyle, including dietary changes that reduce body weight, fat, and alcohol intake and increase potassium and calcium intake,9 as well as exercise,1011 reduce or normalize BP in many patients. Inherited BPThe identification of variant (allelic) genes that contribute to the development of hypertension is complicated by the fact that the 2 phenotypes that determine BP, cardiac output and total peripheral resistance, are controlled by intermediary phenotypes, including the autonomic nervous system, vasopressor/vasodepressor hormones, the structure of the cardiovascular system, body fluid volume and renal function, and many others. Furthermore, these intermediary phenotypes are also controlled by complex mechanisms including BP itself.12 Thus there are many genes that could participate in the development of hypertension. The influence of genes on BP has been suggested by family studies demonstrating associations of BP among siblings and between parents and children. There is a better association among BP values in biological children than in adopted children and in identical as opposed to nonidentical twins. BP variability attributed to all genetic factors varies from 25% in pedigree studies to 65% in twin studies. Furthermore, genetic factors also influence behavioral patterns, which might lead to BP elevation. For example, a tendency toward obesity or alcoholism will be influenced by both genetic and environmental factors; thus the proportion of BP variability caused by inheritance is difficult to determine and may vary in different populations. Mutations in at least 10 genes have been shown to raise or lower BP through a common pathway by increasing or decreasing salt and water reabsorption by the nephron.1314 The genetic mutations responsible for 3 rare forms of mendelian (monogenic) hypertensive syndromes−glucocorticoid-remediable aldosteronism (GRA), Liddle's syndrome, and apparent mineralocorticoid excess−have been identified, whereas in a fourth, autosomal dominant hypertension with brachydactyly, the gene is not yet identified but has been mapped to chromosome 12 (12p). Subtle variations in one of these genes may also cause some forms of "essential" hypertension. For a review of the mutations that cause a decrease in BP, see Lifton.13Glucocorticoid-Remediable AldosteronismThis is an autosomal dominant form of monogenic hypertension in which aldosterone secretion is regulated by adrenocorticotropic hormone. Glucocorticoid treatment causes BP to decrease and gives the syndrome its name. The genetic mutation that causes GRA has been identified by Lifton14 as a chimeric gene fusing nucleotide sequences of the promoter-regulatory region of 11β-hydroxylase (controlled by adrenocorticotropic hormone) and the structural portion of the aldosterone synthase gene. The chimeric gene results from a meiotic mismatch and unequal crossing over. The patients are usually thought to have primary aldosteronism because they exhibit volume expansion, metabolic alkalosis with hypokalemia, low plasma renin, and high aldosterone. Most of the patients first described as having GRA showed severe hypertension and died prematurely from stroke. However, with the development of direct genetic testing, the BP of patients with this syndrome was found to cover a wide range, including normotensive levels.1516 In patients with GRA and normal BP, expression of the chimeric gene may be variable, but because steroid levels are similar in patients with severe and mild hypertension, this seems unlikely. It is also possible that the genetic background of the trait (other than the chimeric mutation), such as high renal kallikrein, places the inherited BP of these subjects in the low or ideal normal range and the mutation causes BP to increase to high normal or hypertensive stage 1. Thus the final BP would be the combined result of the inherited BP (including the genetic mutation) and the increase in BP caused by hypertensinogenic factors such as salt. Liddle's SyndromeThis is an autosomal dominant form of monogenic hypertension that results from mutations in the amiloride-sensitive epithelial sodium channel, leading to increased channel activity.17 The mutations reported to date result in the elimination of 45 to 75 amino acids from the cytoplasmic carboxyl terminus of β- or γ-subunits of the channel; thus Liddle's syndrome is genetically heterogeneous. It is characterized by the early onset of hypertension with hypokalemia and suppression of both plasma renin activity and aldosterone, the latter differentiating this syndrome from primary aldosteronism. Both the hypertension and the hypokalemia vary in severity, raising the possibility that some patients classified as having salt-sensitive essential hypertension actually have Liddle's syndrome.18 It is also possible that high BP in blacks, who are frequently salt-sensitive, is due to a polymorphism in one of the sodium channel genes or in one of the genes of systems that regulate it, causing its activity to increase. Apparent Mineralocorticoid ExcessThis is an autosomal recessive form of monogenic juvenile hypertension that results from a mutation in the renal-specific isoform 11β-hydroxysteroid dehydrogenase gene.19 Normally this enzyme converts cortisol to the inactive metabolite cortisone. In the distal nephron this is important because cortisol and aldosterone have a similar affinity for the mineralocorticoid receptor. The enzymatic deficiency allows the mineralocorticoid receptors in the nephron to be occupied and activated by cortisol, causing sodium and water retention, volume expansion, low renin, low aldosterone, and more importantly, a salt-sensitive form of hypertension. Thus this gene may be a locus for salt-sensitive essential hypertension. Autosomal Dominant Hypertension With BrachydactylyIn this monogenic syndrome, hypertension and brachydactyly are always inherited together (100% cosegregation).4 Affected persons are shorter than nonaffected relatives. The gene for hypertension has been mapped to the short arm of chromosome 12 (12p) in a large Turkish kindred. Two other families with this syndrome have been reported, 1 in Canada and 1 in the United States. In addition, the study of a Japanese child with hypertension and type E brachydactyly has allowed the area on 12p containing the gene mutation to be pinpointed further, although the gene responsible for this syndrome has not yet been cloned. Unlike the other 3 autosomal forms of hypertension, BP is not affected by volume expansion and the underlying mechanism is not known. Thus identification of the gene responsible may help clarify some of the genetic alterations in essential hypertension. Essential or Primary HypertensionThe genetic alterations responsible for inherited "essential" hypertension remain largely unknown.4 Results from family studies suggest several possible intermediary phenotypes (genetic traits) that may be related to inherited high BP, such as high sodium-lithium countertransport, low urinary kallikrein excretion, high fasting plasma insulin concentrations, high-density LDL subfractions, fat pattern index, and body mass index (BMI).12 Jeunemaitre et al2021 first reported a polymorphism in the angiotensinogen gene linked with essential hypertension in hypertensive siblings from Utah and France. This polymorphism consists of a substitution of thymidine for cytosine in nucleotide 704, which causes substitution of methionine for threonine at position 235 (M235T) and is associated with increased concentrations of plasma angiotensinogen. This variant appears to be in tight linkage disequilibrium with a promoter mutation in which adenine replaces guanine (-6A) upstream from the initiation side of transcription.22 Tests of promoter activity suggest that this nucleotide substitution increases the rate of gene transcription, which may explain the higher angiotensinogen concentration found in subjects with the variant M235T.22 Many studies have been published on various racial groups with regard to the association between allelic variations in angiotensinogen and hypertension.23 However, these variations explain only a small part of the BP variation (≈6%). Furthermore, plasma angiotensinogen concentrations, though higher in patients with the polymorphism, clearly overlap with normotensive patients. Polymorphisms and mutations in other genes such as angiotensin-converting enzyme, β2-adrenergic receptor, α-adducin, angiotensinase C, renin-binding protein, G-protein β3-subunit, atrial natriuretic factor, and the insulin receptor have also been linked to the development of essential hypertension; however, most of them show a weak association if any, and most of these studies need further confirmation. Thus these gene alterations will not be discussed here because they go beyond the scope of this review (see Luft4 ).Hypertensinogenic FactorsThere is evidence that obesity, insulin resistance, high alcohol intake, high salt intake, a sedentary lifestyle, stress, dyslipidemia, and low potassium or calcium intake increase BP in susceptible subjects. Here we will briefly discuss obesity and insulin resistance; other hypertensinogenic factors will be discussed in the section "Lifestyle Modification."Obesity and Insulin ResistanceObesity, and obesity, is the main hypertensinogenic It was estimated in the study that is associated with a mm Hg increase in systolic is also the cause of insulin resistance, left and Thus obesity is an important cardiovascular its incidence and prevalence are in most industrialized and in the United States has The between BP and body fat is not to the but is continuous throughout the range of body A direct association between hypertension and in by the in has been in and population studies from early to old A of is considered normal or whereas a of to with increases the risk of high BP by and the risk of insulin resistance by Thus insulin resistance is in many patients with obesity and hypertension. The mechanism by which obesity BP is not but increased is associated with an increase in plasma volume and cardiac both these alterations and BP can be by in both normotensive and hypertensive even when sodium intake is BP in is and fasting insulin is the of this In these BP by 10 mm Hg changing from 2 on a to a When some of these subjects by BP by 10 mm Hg and salt was no longer present. The that sodium fasting plasma plasma aldosterone, and plasma the that BP is to dietary sodium and that this may be due to the combined of and increased activity of the sympathetic nervous It is not clear whether body fat by is a factor because in for 1 3 BP, and this decrease was mainly in those who high fasting insulin and insulin levels in to In this study was not a factor because the subjects on a and actually gained an average of the which that plasma insulin by a different mechanism than of body These studies can be as that high plasma insulin causes salt and that decreasing insulin resistance by or BP. Furthermore, hypertensive subjects are more to exhibit insulin resistance than normotensive the other insulin by has a In subjects with hypertension there is resistance to the of insulin on However, in addition to this metabolic insulin increases both sympathetic nerve activity and sodium and water retention, and it could be that the hypertension is due to the of resistance to these secondary of factor and a that have also been in the of hypertension. although the mechanisms by which obesity and insulin resistance increase BP remain it is clear that these increases in BP are on the inherited of of the evaluation are to determine the and of target organ and for specific causes of hypertension hypertensinogenic factors and other CVD risk factors; and the patient to facilitate the of therapy and define and of BP by the is the most important part of the evaluation and of the patient and be in a 2) with the use of and A is a or a to an arm Two or 3 measurements be at and at least 2 be allowed between The diastolic is at the level when of BP by patients or family and/or BP the diagnosis and the of hypertension. BP values the are lower and better with target organ than BP measurements by of BP has several including hypertension from hypertension that only in the the to antihypertensive to treatment by the patient a in his or her and by the need for BP or of BP is for many patients with high BP, those who to be to antihypertensive A of or BP measurements is that and BP be and that and in to BP be and be and a in all patients The assessment the described in Table It help to known, causes of high the or of target organ and and other CVD or comorbid conditions that might or Tests and only blood blood fasting total and high-density or and a indicated in patients for the diagnosis of secondary hypertension and/or comorbid conditions urinary protein, of fasting and plasma renin is Part of a Part of this will be published in the 1, of 1. of hypertensinogenic factors such as obesity and alcohol intake on systolic and diastolic BP the stage of inherited BP to without the of the hypertensinogenic with normal or high normal inherited BP hypertensive stage 1 when BP is increased by a hypertensinogenic In patients with inherited hypertension in 1 to hypertension more severe when hypertensinogenic factors are among genetic and environmental factors in the development of hypertension. side of environmental factors and multiple genes responsible for high BP and intermediary The result of these intermediary phenotypes is blood pressure with a normal distribution skewed to the right. the theoretical BP of the population that is not affected by hypertensinogenic factors; area systolic BP in the hypertensive range. and dotted populations in which 1 or 2 hypertensinogenic factors high alcohol intake) have been that in these 2 populations the distribution are to the right and the number of hypertensive individuals is increased when hypertensinogenic factors are Table 1. and of Blood Pressure mm mm 1 2 3 systolic a patient's systolic and

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Heart rate variability

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

Relationship of patient and medical characteristics to health status in children and adolescents after the Fontan procedure.

Background: After the Fontan procedure, patients are at risk for suboptimal health status related to their complex healthcare experience, physiological limitations, medical complications, and guarded long-term prognosis. Methods and results: In the Pediatric Heart Network cross-sectional study of Fontan survivors 6 to 18 years of age, parents completed the Child Health Questionnaire, and scores were related in multivariable analysis to patient and medical characteristics obtained from medical record review. For 537 patients (mean age at study, 11.9 years; 60% male) with a median age at Fontan of 2.8 years (range, 0.7 to 14.6 years), parent-reported patient morbidities included deficits in vision in 33%, speech in 27%, and hearing in 7%, as well as problems with attention in 46%, learning in 43%, development in 24%, behavior in 23%, anxiety in 17%, and depression in 8%. Child Health Questionnaire summary scores were significantly lower than the US population sample for Physical Functioning (mean Z score, -0.47+/-1.19; P<0.001) and Psychosocial Functioning (-0.28+/-1.08; P<0.001). Parent-reported medical conditions and long-term and current medical problems explained the greatest amount of variation in the Physical Functioning scores. Parent-reported patient conditions, including behavior, learning, anxiety, and attention problems and depression, explained the greatest amount of variation in the Psychosocial Functioning scores. Lower family income had a negative impact on both Physical and Psychosocial Functioning. Conclusions: There are deficits in health status in children and adolescents after the Fontan procedure. Strategies to address this problem might emphasize coordinated and effective prevention, detection, and management of noncardiac and psychosocial conditions, as well as specific targeting of patients from low-income households.

Circulation · 118 citationsread the source →

Prevalence and correlates of stress and burnout among U.S. healthcare workers during the COVID-19 pandemic: A national cross-sectional survey study.

Background: COVID-19 has put extraordinary stress on healthcare workers. Few studies have evaluated stress by worker role, or focused on experiences of women and people of color. Methods: The "Coping with COVID" survey assessed US healthcare worker stress. A stress summary score (SSS) incorporated stress, fear of exposure, anxiety/depression and workload (Omega 0.78). Differences from mean were expressed as Cohen's d Effect Sizes (ESs). Regression analyses tested associations with stress and burnout. Findings: Between May 28 and October 1, 2020, 20,947 healthcare workers responded from 42 organizations (median response rate 20%, Interquartile range 7% to 35%). Sixty one percent reported fear of exposure or transmission, 38% reported anxiety/depression, 43% suffered work overload, and 49% had burnout. Stress scores were highest among nursing assistants, medical assistants, and social workers (small to moderate ESs, p < 0.001), inpatient vs outpatient workers (small ES, p < 0.001), women vs men (small ES, p < 0.001), and in Black and Latinx workers vs Whites (small ESs, p < 0.001). Fear of exposure was prevalent among nursing assistants and Black and Latinx workers, while housekeepers and Black and Latinx workers most often experienced enhanced meaning and purpose. In multilevel models, odds of burnout were 40% lower in those feeling valued by their organizations (odds ratio 0.60, 95% CIs [0.58, 0.63], p< 0.001). Interpretation: Stress is higher among nursing assistants, medical assistants, social workers, inpatient workers, women and persons of color, is related to workload and mental health, and is lower when feeling valued.

EClinicalMedicine · 352 citationsread the source →

Avoiding holiday seasonal weight gain with nutrient-supported intermittent energy restriction: a pilot study.

This pilot randomised controlled study evaluated the effects of a nutrient-supported intermittent energy restriction nutrition programme to prevent weight gain in healthy overweight adults during the 6-week winter holiday period between Thanksgiving and New Year. For 52 d, twenty-two overweight adults (mean age 41·0 years, BMI 27·3 kg/m2) were assigned to either the nutrition programme (n 10; two fasting days of 730 kcal/d (3050 kJ/d) of balanced shake and dietary supplements to support weight management efforts, followed by 5 d of habitual diet) or a control group (n 12; habitual diet). A significant weight loss from baseline (pre-holiday 10 d before Thanksgiving) to day 52 (post-holiday 3 January) was observed in the nutrition programme (75·0 (sd 9·8) v. 76·3 (sd 9·8) kg; P < 0·05). Body weight did not significantly change in the control group and there was no between-group difference. Increases from baseline in fasting insulin (42·9 %; P = 0·0256), updated homoeostasis model assessment (HOMA2) (43 %; P = 0·025), LDL-cholesterol (8·4 %; P = 0·0426) and total cholesterol (7·1 %; P = 0·0154) levels were also reported in the control group. In the nutrition programme group, baseline HDL-cholesterol and TAG levels measured after two fasting days increased (13 %; P = 0·0245) and decreased (22·8 %; P = 0·0416), respectively. There was no significant change in HOMA2. Between-group differences in changes in insulin levels (P = 0·0227), total cholesterol:HDL-cholesterol ratio (P = 0·0419) and HOMA2 (P = 0·0210) were significant. Overall compliance rate was 98 % and no severe adverse events were reported. These preliminary findings suggest that this intermittent energy restriction intervention might support weight management efforts and help promote metabolic health during the winter holiday season.

Journal of nutritional science · 21 citationsread the source →

Stress response and the adolescent transition: performance versus peer rejection stressors.

Little is known about normative variation in stress response over the adolescent transition. This study examined neuroendocrine and cardiovascular responses to performance and peer rejection stressors over the adolescent transition in a normative sample. Participants were 82 healthy children (ages 7-12 years, n = 39, 22 females) and adolescents (ages 13-17, n = 43, 20 females) recruited through community postings. Following a habituation session, participants completed a performance (public speaking, mental arithmetic, mirror tracing) or peer rejection (exclusion challenges) stress session. Salivary cortisol, salivary alpha amylase (sAA), systolic and diastolic blood pressure (SBP, DBP), and heart rate were measured throughout. Adolescents showed significantly greater cortisol, sAA, SBP, and DBP stress response relative to children. Developmental differences were most pronounced in the performance stress session for cortisol and DBP and in the peer rejection session for sAA and SBP. Heightened physiological stress responses in typical adolescents may facilitate adaptation to new challenges of adolescence and adulthood. In high-risk adolescents, this normative shift may tip the balance toward stress response dysregulation associated with depression and other psychopathology. Specificity of physiological response by stressor type highlights the importance of a multisystem approach to the psychobiology of stress and may also have implications for understanding trajectories to psychopathology.

Development and psychopathology · 408 citationsread the source →

Association between physical exercise and mental health in 1·2 million individuals in the USA between 2011 and 2015: a cross-sectional study.

Background: Exercise is known to be associated with reduced risk of all-cause mortality, cardiovascular disease, stroke, and diabetes, but its association with mental health remains unclear. We aimed to examine the association between exercise and mental health burden in a large sample, and to better understand the influence of exercise type, frequency, duration, and intensity. Methods: In this cross-sectional study, we analysed data from 1 237 194 people aged 18 years or older in the USA from the 2011, 2013, and 2015 Centers for Disease Control and Prevention Behavioral Risk Factors Surveillance System survey. We compared the number of days of bad self-reported mental health between individuals who exercised and those who did not, using an exact non-parametric matching procedure to balance the two groups in terms of age, race, gender, marital status, income, education level, body-mass index category, self-reported physical health, and previous diagnosis of depression. We examined the effects of exercise type, duration, frequency, and intensity using regression methods adjusted for potential confounders, and did multiple sensitivity analyses. Findings: Individuals who exercised had 1·49 (43·2%) fewer days of poor mental health in the past month than individuals who did not exercise but were otherwise matched for several physical and sociodemographic characteristics (W=7·42 × 1010, p<2·2 × 10-16). All exercise types were associated with a lower mental health burden (minimum reduction of 11·8% and maximum reduction of 22·3%) than not exercising (p<2·2 × 10-16 for all exercise types). The largest associations were seen for popular team sports (22·3% lower), cycling (21·6% lower), and aerobic and gym activities (20·1% lower), as well as durations of 45 min and frequencies of three to five times per week. Interpretation: In a large US sample, physical exercise was significantly and meaningfully associated with self-reported mental health burden in the past month. More exercise was not always better. Differences as a function of exercise were large relative to other demographic variables such as education and income. Specific types, durations, and frequencies of exercise might be more effective clinical targets than others for reducing mental health burden, and merit interventional study. Funding: Cloud computing resources were provided by Microsoft.

The lancet. Psychiatry · 681 citationsread the source →

Non-familial intergenerational interventions and their impact on social and mental wellbeing of both younger and older people-A mapping review and evidence and gap map.

Background: Opportunities for social connection between generations in the UK have diminished over the last few decades because of changes in the way that we live and work. The decline in communal spaces such as libraries, youth clubs and community centres mean that there are fewer opportunities to meet and mix socially with other generations outside our own families. Increased working hours, improved technology, changes in family patterns, relationship breakdowns within families and migration are also believed to be contributory factors to generation segregation. There are many potential economic, social and political impacts of generations living separate and parallel lives, for example, higher health and social care costs, an undermining of trust between generations reduced social capital, a reliance on the media to form understanding of others' viewpoints and higher levels of anxiety and loneliness. Intergenerational programmes and activities can take many forms and are delivered in many settings.  Evidence suggests that intergenerational activity can have a positive impact on participants, for example, in reducing loneliness and exclusion for both older people and children and young people, improving mental health, increasing mutual understanding and addressing important issues such as ageism, housing and care. There are currently no other EGMs that exist that address this type of intervention; however, it would complement existing EGMs addressing child welfare. Objectives: To identify, appraise and bring together the evidence on the use of intergenerational practice, to answer the following specific research questions: What is the volume, nature and diversity of research on, and evaluation of, intergenerational practice and learning?What approaches have been used to deliver intergenerational activities and programmes that may be relevant to providing such services during and in the subsequent recovery from the COVID-19 pandemic?What promising intergenerational activities and programmes have been developed and are being used but have not yet been subject to formal evaluation? Search methods: We searched MEDLINE (via OvidSp), EMBASE (via OvidSp), PsycINFO (via OvidSp), CINAHL (via EBSCOHost), Social Policy and Practice (via OvidSp), Health Management Information Consortium (via OvidSp), Ageline (via EBSCOhost), ASSIA (via ProQuest), Social Science Citations Index (via Web of Science), ERIC (via EBSCOhost), Community Care Inform Children, Research in Practice for Children, ChildData (via Social Policy and Practice), the Campbell Library, the Cochrane Database of Systematic Reviews and the CENTRAL database between 22 and 30 July 2021. We searched for additional grey literature via the Conference Proceedings Citation Index (via Web of Science) and ProQuest Dissertation & Theses Global and via relevant organisation websites, for example, Age UK, Age International, the Centre for Ageing Better, Barnado's, Children's Commission, UNICEF, Generations Working Together, the Intergenerational Foundation, Linking Generations and The Beth Johnson Foundation) and the Ottawa initiative called Older Adults and Students for Intergenerational support. Selection criteria: Any intervention that brings older and younger people together with the purpose of interacting to achieve positive health and/or social and/or educational outcomes from any study design including systematic reviews, randomised controlled studies, observational studies, surveys and qualitative studies are included. The titles and abstracts, and later full texts, of records identified by the search methods were screened against inclusion criteria by two independent reviewers. Data collection and analysis: Data extraction was undertaken by one reviewer and checked by a second with any inconsistencies identified and resolved through discussion. The data extraction tool was developed on EPPI reviewer and was modified and tested through stakeholder and advisor consultation, and piloting of the process. The tool was informed by the research question and the structure of the map. We did not undertake quality appraisal of the included studies. Main results: Our searches identified 12,056 references, after screening 500 research articles were included in the evidence gap map conducted across 27 countries. We identified 26 systematic reviews, 236 quantitative comparative studies (of which 38 were randomised controlled trials), 227 were qualitative studies (or had a qualitative element), 105 were observational studies (or had elements of observational methods) and 82 used a mixed methods approach. The outcomes reported in the research cover mental health (n = 73), physical health (n = 62), attainment and knowledge (n = 165), agency (n = 174), mental wellbeing (n = 224), loneliness and social isolation (n = 54), attitudes towards the other generation (n = 283), intergenerational interactions (n = 196), peer interactions (n = 30) and health promotion (n = 23) and including mutual outcomes such as the impact on community (n = 37) and perceptions on the sense of community (n = 43). Gaps in the evidence that were identified include: research that reports on mutual, societal and community outcomes of intergenerational interventions; more research on interventions classified as levels 1-4 and level 7 on the Intergenerational Engagement Scale, mental health, loneliness, social isolation, peer interactions, physical health and health promotion outcomes in children and young people; health promotion in older people; outcomes centred on care giver wellbeing, mental health and attitudes; economic outcomes; process outcomes and adverse or unexpected outcomes. Authors’ conclusions: Whilst a substantional amount of research on intergenerational interventions has been identified in this EGM, as well as the gaps identified above, there is a need to explore promising interventions not yet formally evaluated. Research on this topic is gradually increasing, and systematic reviews will be important to determine how and why interventions are or are not beneficial. However, the primary research needs to build more cohesively so that the findings can be comparable and avoid research waste. The EGM presented here will nevertheless be a useful resource for decision-makers allowing them to explore the evidence with regard to the different interventions that may be relevant to their population needs and the settings or resources available to them.

Campbell systematic reviews · 25 citationsread the source →

Father involvement, maternal depression and child nutritional outcomes in Soweto, South Africa.

Father involvement in South Africa is low, despite evidence that it can improve maternal and child health and wellbeing. Within a larger randomised controlled trial, we assessed whether father involvement during and after pregnancy increased birth weight and exclusive breastfeeding through improved maternal mental health. At 6-week postnatal, mothers completed questionnaires on birth, feeding practices, social support, father involvement and postnatal depression. Father involvement during pregnancy was measured by their attendance at antenatal care and the study intervention, whereas postnatal involvement was measured by attendance at antenatal care and type of paternal support provided. Structural equation modelling was used to identify associations between father involvement, maternal depression, low birth weight and exclusive breastfeeding. Among the 212 mother-baby pairs, father involvement was very low with only 43%, 33% and 1% of partners attending early ultrasound, antenatal care and the birth of the child, respectively. Twenty-nine percent of the mothers showed signs of depression during pregnancy, compared with 7% after birth. Eighteen percent of the infants were born low birth weight, and 57% of mothers reported exclusively breastfeeding at 6 weeks. Father involvement was directly associated with postnatal depression, but it did not directly or indirectly impact exclusive breastfeeding or low birth weight. We conclude that postnatal father involvement can improve postnatal maternal depression and that men would benefit from specific guidance on how they can support mothers during and after pregnancy.

Maternal & child nutrition · 33 citationsread the source →

Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK.

Background: A rise in the incidence of some autoimmune disorders has been described. However, contemporary estimates of the overall incidence of autoimmune diseases and trends over time are scarce and inconsistent. We aimed to investigate the incidence and prevalence of 19 of the most common autoimmune diseases in the UK, assess trends over time, and by sex, age, socioeconomic status, season, and region, and we examine rates of co-occurrence among autoimmune diseases. Methods: In this UK population-based study, we used linked primary and secondary electronic health records from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex and ethnicity. Eligible participants were men and women (no age restriction) with acceptable records, approved for Hospital Episodes Statistics and Office of National Statistics linkage, and registered with their general practice for at least 12 months during the study period. We calculated age and sex standardised incidence and prevalence of 19 autoimmune disorders from 2000 to 2019 and used negative binomial regression models to investigate temporal trends and variation by age, sex, socioeconomic status, season of onset, and geographical region in England. To characterise co-occurrence of autoimmune diseases, we calculated incidence rate ratios (IRRs), comparing incidence rates of comorbid autoimmune disease among individuals with a first (index) autoimmune disease with incidence rates in the general population, using negative binomial regression models, adjusted for age and sex. Findings: Among the 22 009 375 individuals included in the study, 978 872 had a new diagnosis of at least one autoimmune disease between Jan 1, 2000, and June 30, 2019 (mean age 54·0 years [SD 21·4]). 625 879 (63·9%) of these diagnosed individuals were female and 352 993 (36·1%) were male. Over the study period, age and sex standardised incidence rates of any autoimmune diseases increased (IRR 2017-19 vs 2000-02 1·04 [95% CI 1·00-1·09]). The largest increases were seen in coeliac disease (2·19 [2·05-2·35]), Sjogren's syndrome (2·09 [1·84-2·37]), and Graves' disease (2·07 [1·92-2·22]); pernicious anaemia (0·79 [0·72-0·86]) and Hashimoto's thyroiditis (0·81 [0·75-0·86]) significantly decreased in incidence. Together, the 19 autoimmune disorders examined affected 10·2% of the population over the study period (1 912 200 [13·1%] women and 668 264 [7·4%] men). A socioeconomic gradient was evident across several diseases, including pernicious anaemia (most vs least deprived area IRR 1·72 [1·64-1·81]), rheumatoid arthritis (1·52 [1·45-1·59]), Graves' disease (1·36 [1·30-1·43]), and systemic lupus erythematosus (1·35 [1·25-1·46]). Seasonal variations were observed for childhood-onset type 1 diabetes (more commonly diagnosed in winter) and vitiligo (more commonly diagnosed in summer), and regional variations were observed for a range of conditions. Autoimmune disorders were commonly associated with each other, particularly Sjögren's syndrome, systemic lupus erythematosus, and systemic sclerosis. Individuals with childhood-onset type 1 diabetes also had significantly higher rates of Addison's disease (IRR 26·5 [95% CI 17·3-40·7]), coeliac disease (28·4 [25·2-32·0]), and thyroid disease (Hashimoto's thyroiditis 13·3 [11·8-14·9] and Graves' disease 6·7 [5·1-8·5]), and multiple sclerosis had a particularly low rate of co-occurrence with other autoimmune diseases. Interpretation: Autoimmune diseases affect approximately one in ten individuals, and their burden continues to increase over time at varying rates across individual diseases. The socioeconomic, seasonal, and regional disparities observed among several autoimmune disorders in our study suggest environmental factors in disease pathogenesis. The inter-relations between autoimmune diseases are commensurate with shared pathogenetic mechanisms or predisposing factors, particularly among connective tissue diseases and among endocrine diseases. Funding: Research Foundation Flanders.

Lancet (London, England) · 508 citationsread the source →

Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.

Background: Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods: We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings: In 2019, there were 12·2 million (95% UI 11·0-13·6) incident cases of stroke, 101 million (93·2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6·55 million (6·00-7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8-12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1-6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0-73·0), prevalent strokes increased by 85·0% (83·0-88·0), deaths from stroke increased by 43·0% (31·0-55·0), and DALYs due to stroke increased by 32·0% (22·0-42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0-18·0), mortality decreased by 36·0% (31·0-42·0), prevalence decreased by 6·0% (5·0-7·0), and DALYs decreased by 36·0% (31·0-42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0-24·0) and incidence rates increased by 15·0% (12·0-18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5-3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5-3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57-8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97-3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01-1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7-90·8] DALYs or 55·5% [48·2-62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3-48·6] DALYs or 24·3% [15·7-33·2]), high fasting plasma glucose (28·9 million [19·8-41·5] DALYs or 20·2% [13·8-29·1]), ambient particulate matter pollution (28·7 million [23·4-33·4] DALYs or 20·1% [16·6-23·0]), and smoking (25·3 million [22·6-28·2] DALYs or 17·6% [16·4-19·0]). Interpretation: The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Funding: Bill & Melinda Gates Foundation.

The Lancet. Neurology · 5441 citationsread the source →

Effectiveness of Early Time-Restricted Eating for Weight Loss, Fat Loss, and Cardiometabolic Health in Adults With Obesity: A Randomized Clinical Trial.

Importance: It is unclear how effective intermittent fasting is for losing weight and body fat, and the effects may depend on the timing of the eating window. This randomized trial compared time-restricted eating (TRE) with eating over a period of 12 or more hours while matching weight-loss counseling across groups. Objective: To determine whether practicing TRE by eating early in the day (eTRE) is more effective for weight loss, fat loss, and cardiometabolic health than eating over a period of 12 or more hours. Design, setting, and participants: The study was a 14-week, parallel-arm, randomized clinical trial conducted between August 2018 and April 2020. Participants were adults aged 25 to 75 years with obesity and who received weight-loss treatment through the Weight Loss Medicine Clinic at the University of Alabama at Birmingham Hospital. Interventions: All participants received weight-loss treatment (energy restriction [ER]) and were randomized to eTRE plus ER (8-hour eating window from 7:00 to 15:00) or control eating (CON) plus ER (≥12-hour window). Main outcomes and measures: The co-primary outcomes were weight loss and fat loss. Secondary outcomes included blood pressure, heart rate, glucose levels, insulin levels, and plasma lipid levels. Results: Ninety participants were enrolled (mean [SD] body mass index, 39.6 [6.7]; age, 43 [11] years; 72 [80%] female). The eTRE+ER group adhered 6.0 (0.8) days per week. The eTRE+ER intervention was more effective for losing weight (-2.3 kg; 95% CI, -3.7 to -0.9 kg; P = .002) but did not affect body fat (-1.4 kg; 95% CI, -2.9 to 0.2 kg; P = .09) or the ratio of fat loss to weight loss (-4.2%; 95% CI, -14.9 to 6.5%; P = .43). The effects of eTRE+ER were equivalent to reducing calorie intake by an additional 214 kcal/d. The eTRE+ER intervention also improved diastolic blood pressure (-4 mm Hg; 95% CI, -8 to 0 mm Hg; P = .04) and mood disturbances, including fatigue-inertia, vigor-activity, and depression-dejection. All other cardiometabolic risk factors, food intake, physical activity, and sleep outcomes were similar between groups. In a secondary analysis of 59 completers, eTRE+ER was also more effective for losing body fat and trunk fat than CON+ER. Conclusions and relevance: In this randomized clinical trial, eTRE was more effective for losing weight and improving diastolic blood pressure and mood than eating over a window of 12 or more hours at 14 weeks. Trial registration: ClinicalTrials.gov Identifier: NCT03459703.

JAMA internal medicine · 202 citationsread the source →

Socioeconomic disparities in first stroke incidence, quality of care, and survival: a nationwide registry-based cohort study of 44 million adults in England.

Background: We aimed to estimate socioeconomic disparities in the incidence of hospitalisation for first-ever stroke, quality of care, and post-stroke survival for the adult population of England. Methods: In this cohort study, we obtained data collected by a nationwide register on patients aged 18 years or older hospitalised for first-ever acute ischaemic stroke or primary intracerebral haemorrhage in England from July 1, 2013, to March 31, 2016. We classified socioeconomic status at the level of Lower Super Output Areas using the Index of Multiple Deprivation, a neighbourhood measure of deprivation. Multivariable models were fitted to estimate the incidence of hospitalisation for first stroke (negative binomial), quality of care using 12 quality metrics (multilevel logistic), and all-cause 1 year case fatality (Cox proportional hazards). Findings: Of the 43·8 million adults in England, 145 324 were admitted to hospital with their first-ever stroke: 126 640 (87%) with ischaemic stroke, 17 233 (12%) with intracerebral haemorrhage, and 1451 (1%) with undetermined stroke type. We observed a socioeconomic gradient in the incidence of hospitalisation for ischaemic stroke (adjusted incidence rate ratio 2·0, 95% CI 1·7-2·3 for the most vs least deprived deciles) and intracerebral haemorrhage (1·6, 1·3-1·9). Patients from the lowest socioeconomic groups had first stroke a median of 7 years earlier than those from the highest (p<0·0001), and had a higher prevalence of pre-stroke disability and diabetes. Patients from lower socioeconomic groups were less likely to receive five of 12 care processes but were more likely to receive early supported discharge (adjusted odds ratio 1·14, 95% CI 1·07-1·22). Low socioeconomic status was associated with a 26% higher adjusted risk of 1-year mortality (adjusted hazard ratio 1·26, 95% CI 1·20-1·33, for highest vs lowest deprivation decile), but this gradient was largely attenuated after adjustment for the presence of pre-stroke diabetes, hypertension, and atrial fibrillation (1·11, 1·05-1·17). Interpretation: Wide socioeconomic disparities exist in the burden of ischaemic stroke and intracerebral haemorrhage in England, most notably in stroke hospitalisation risk and case fatality and, to a lesser extent, in the quality of health care. Reducing these disparities requires interventions to improve the quality of acute stroke care and address disparities in cardiovascular risk factors present before stroke. Funding: NHS England and the Welsh Government.

The Lancet. Public health · 104 citationsread the source →

Child behavior and sibling relationship quality: A cross-lagged analysis.

Bidirectional associations between sibling relationships and children's problem behaviors are robust, and links with prosocial behavior have also been reported. Using cross-lagged models, we were able to conservatively test temporal directions of links between positive and negative aspects of sibling relationships and children's prosocial behavior and conduct problems across a 3-year time span in middle childhood. The Avon Longitudinal Study of Parents and Children (ALSPAC; http://www.bristol.ac.uk/alspac/researchers/data-access/data-dictionary/) is an ongoing population-based study designed to investigate the effects of a wide range of factors on children's health and development. For the purposes of the current analyses, we included 2,043 ALSPAC families who had just 1 older sibling as well as the target child, with an age gap of no more than 5 years. Mothers reported about the quality of the sibling relationship and both children's prosocial behavior and conduct problems when the target child was 4 years of age and again when the target child was 7 years old. Confirming our hypothesis, individual child behavior was predictive of sibling relationship quality, and sibling relationship quality was predictive of later child behavior, providing robust evidence of bidirectionality for both prosocial behavior and conduct problems. It would be consistent to expect that an improvement in either sibling relationship quality or individual children's behavior could have a positive spill over effect. We also found evidence of older sibling dominance in the domain of prosocial behavior and the positive aspects of sibling interaction. (PsycINFO Database Record

Journal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43) · 18 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 →

An objective assessment of children's exposure to brand marketing in New Zealand (Kids'Cam): a cross-sectional study.

Background: Marketing promotes values of consumerism and overconsumption, and negatively affects children's wellbeing and psychological development. The threat marketing poses to planetary health is just being realised. However, little is known about children's exposure to marketing at an aggregate level. Using an objective method of wearable cameras, we aimed to determine the nature and extent of children's exposure to marketing. Methods: Kids'Cam was a cross-sectional study of children aged 11-13 years in New Zealand, from which we randomly selected a sample of 90 children. Children wore cameras from when they woke up until they went to sleep for four consecutive days (Thursday-Sunday) that captured images at an angle of 136° every 7 s for exposure to marketing. Marketing brands were categorised into three groups: core food and social marketing messages, harmful commodities (eg, non-core food, alcohol, and gambling), or other. Exposure rates by marketing medium, setting, and product category were calculated using negative binomial regression models. Findings: From June 21, 2014, to June 30, 2015, we recruited 168 children, and randomly selected data from 90 children for the present study. Children in this study were exposed to a mean of 554 brands per 10 h day (95% CI 491-625), nearly a brand a minute, through multiple mediums (predominantly brand labels [36% of exposures] and product packaging [22%]) and mostly in schools (43%) and at home (30%). Food and beverages (20% of exposures) were the dominant product category. The most pervasive marketing brands typically sold a range of products across more than one product category (eg, children were exposed to Nike on average 20 exposures per day). Children were exposed to more than twice as many harmful commodities (mean 76 per 10 h day [95% CI 55-105]) as core food and social marketing messages (32 [26-39]) per day. Interpretation: We found that children are repeatedly exposed to marketing through multiple mediums and across all settings, and our findings suggests that marketing privileges particular messages, for example, marketing of harmful commodities. Given the key role marketing plays in establishing and supporting consumption norms, and perpetuating the normalisation of overconsumption which contributes to environmental degradation, these findings suggest an urgent need to reduce marketing to promote planetary health. Funding: This research was funded by a University of Otago, Dean's Research Grant. The Kids'Cam study was funded by a Health Research Council of New Zealand Programme Grant (13/724).

The Lancet. Planetary health · 10 citationsread the source →

Scaling-up treatment of depression and anxiety: a global return on investment analysis.

Background: Depression and anxiety disorders are highly prevalent and disabling disorders, which result not only in an enormous amount of human misery and lost health, but also lost economic output. Here we propose a global investment case for a scaled-up response to the public health and economic burden of depression and anxiety disorders. Methods: In this global return on investment analysis, we used the mental health module of the OneHealth tool to calculate treatment costs and health outcomes in 36 countries between 2016 and 2030. We assumed a linear increase in treatment coverage. We factored in a modest improvement of 5% in both the ability to work and productivity at work as a result of treatment, subsequently mapped to the prevailing rates of labour participation and gross domestic product (GDP) per worker in each country. Findings: The net present value of investment needed over the period 2016-30 to substantially scale up effective treatment coverage for depression and anxiety disorders is estimated to be US$147 billion. The expected returns to this investment are also substantial. In terms of health impact, scaled-up treatment leads to 43 million extra years of healthy life over the scale-up period. Placing an economic value on these healthy life-years produces a net present value of $310 billion. As well as these intrinsic benefits associated with improved health, scaled-up treatment of common mental disorders also leads to large economic productivity gains (a net present value of $230 billion for scaled-up depression treatment and $169 billion for anxiety disorders). Across country income groups, resulting benefit to cost ratios amount to 2·3-3·0 to 1 when economic benefits only are considered, and 3·3-5·7 to 1 when the value of health returns is also included. Interpretation: Return on investment analysis of the kind reported here can contribute strongly to a balanced investment case for enhanced action to address the large and growing burden of common mental disorders worldwide. Funding: Grand Challenges Canada.

The lancet. Psychiatry · 792 citationsread the source →

Charting the Future of Cancer Health Disparities Research: A Position Statement from the American Association for Cancer Research, the American Cancer Society, the American Society of Clinical Oncology, and the National Cancer Institute

The academic field of cancer health disparities was stimulated by the U.S. civil rights movement. Concerns about civil rights led to concerns about equality in health care. The first publications to make the observation that black Americans have higher rates of death as a result of certain cancers compared with white Americans were published by the early 1970s (1, 2). The discipline concerned with these differences was first called “minority health research” and later “special populations health” or “special populations research.” The National Cancer Institute (NCI) defines cancer health disparities as adverse differences in cancer incidence, cancer prevalence, cancer mortality, cancer survivorship, and burden of cancer or related health conditions that exist among specific population groups in the United States (3). However, with greater and renewed acknowledgment of health disparities as rooted within the context of historical and contextual inequities in the United States, many health disparities are considered health inequities (4).The National Cancer Act of 1971 created the Surveillance, Epidemiology, and End Results (SEER) program within the NCI. This program began collecting incidence, mortality, and survival data by race in the early 1970s from a number of population-based registries around the United States. The SEER program improved documentation of differences in outcomes and analyzed them through its black–white studies (5). These studies especially demonstrated differences in treatment patterns, with a higher proportion of blacks receiving inappropriate cancer care compared with whites. The discipline grew from a focus on black–white differences to encompass differences in outcomes for a number of racial and ethnic groups, as well as for cohorts defined by age, sex, socioeconomic status (SES), and other social determinants of health. There is now even greater appreciation for disparities among communities, whether rural versus urban or even by state or region. The definition of health outcomes also broadened beyond death rates. The field of health disparities was once simply a description of population differences and a call for cultural competence among health care providers. Today, the field is transdisciplinary, integrating basic science, clinical science, policy, epidemiology, and the social sciences. It involves people trained in diverse nonmedical fields, such as education, economics, sociology, religion, geography, and anthropology. The field is also dynamic. It changes as better and more granular statistics, greater understanding of causes of health disparities, and new challenges to mitigate these underlying causes have emerged. As an example, in the 1970s, the breast cancer death rate for black and white American women was the same. Today, the death rate is substantially higher for blacks compared with whites (6). Policy changes have also created opportunities and challenges. The Affordable Care Act has allowed for Medicaid expansion in each state. Expansion has been adopted by 32 states and the District of Columbia. This will create a new challenge, because poor residents of some states have expanded access to care and residents of other states do not. It is essential that any future policy changes should be carefully designed to increase, rather than decrease, equitable access to care throughout the cancer continuum. Population categorizations also are being redefined. The Asian category includes Korean Americans and Pakistani Americans. The Pacific Islander category, often merged with the Asian category, includes native Hawaiians and Samoans. These populations are incredibly heterogeneous and have dramatically different cancer statistics. In 2015, representatives from four leading cancer organizations, the American Association for Cancer Research, the American Cancer Society, the American Society of Clinical Oncology (ASCO), and the NCI, began to meet to discuss the state of health disparities in the United States. These discussions involved the state of cancer health disparities research and what could be done to move it forward. The discussions were purposely not meant as a comprehensive review of cancer health disparities research. Rather, the meeting and the resulting document aimed to identify issues in health disparities research and make specific recommendations to improve the way disparities research is conducted and disseminated. This statement presents a unified strategy among four of the leading cancer organizations in the United States to promote cooperation among investigators in all areas of the cancer health disparities research community, to ensure that cancer research benefits all populations and patients regardless of race, ethnicity, age, gender identity, sexual orientation, SES, or the communities in which they live. Disparities in outcomes across the cancer continuum have been identified in numerous medically underserved populations, including racial and ethnic minorities and patients of lower SES. In addition to individual social status, social contextual and community factors, such as neighborhood safety, social cohesion, availability of healthy foods, and residential segregation, play an important role in health of both individuals and populations. All of these factors can intersect to generate larger disparities (7, 8).To understand and fully address cancer health disparities, complete, consistent, and accurate collection of patient, community, and structural factors that put people at risk for disparate outcomes is essential. Unfortunately, cancer health disparities research has often been fraught with missing, inaccurate, or overly simplified patient-level data, and most research has failed to consider the community-level factors described above (9–11).For the most part, the manner in which data are collected and integrated in disparities research is suboptimal. The literature is characterized by variable methodology for collection of the factors that put patients and communities at risk for disparate care and outcomes. For example, although race and ethnicity are distinct constructs, they are often conflated such that a person is identified as Hispanic without identification of his or her race. Many studies that investigate cancer care or outcomes according to socioeconomic position have only area-level data on socioeconomic position, whereas others use only composite measures. While valuable in many cases in identifying disparities, such measures fall short in providing the richness of data needed to understand an individual's socioeconomic position. Health literacy and numeracy are rarely assessed in practice and are not available in administrative and research databases. Finally, methods for uniform data collection of information on sexual orientation and gender identity are in their infancy, despite calls for such data collection from the Institute of Medicine, among others (12).Disparities in cancer incidence are pronounced and longstanding. Drivers of these disparities are multifactorial and multilevel, and they include sociodemographic factors, access to health care, risk factor profiles and lifestyle/health habits, cultural perceptions, biologic differences, and genetic predisposition. Disparities in cancers for which single etiologic factors account for a substantial proportion of disease (e.g., human papillomavirus and cervical cancer, or Helicobacter pylori and stomach cancer) can be reasonably understood and explained, but disparities for many of the common etiologically heterogeneous cancers, such as breast, prostate, and colorectal cancers, remain much less well understood. Multilevel approaches are needed to advance knowledge relevant to addressing disparities in cancer incidence rates. One approach is to design and implement observational studies focused on a population in which disparities exist to advance knowledge about etiology and to inform novel prevention strategies. A successful example of such an effort is the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium, a multicenter consortium that has combined data and biospecimens from 7,500 African American patients with breast cancer and 17,000 healthy controls, representing the largest study of breast cancer in African American women in the United States (14). It has yielded a number of insights on multilevel risk factors specific to the major molecular subtypes of breast cancer among African American women (15–17).There is also a need for studies focused on identifying the genetic contributors to cancer health disparities. Recent work has focused on the prioritization of candidate variants relevant to prostate cancer risk within the context of genetic ancestry (based on ancestry informative markers) across those with European, African, Japanese, or Latino ancestry (18). Furthermore, the African Ancestry Prostate Cancer Genome-Wide Association Studies (GWAS) Consortium has reported on susceptibility loci for aggressive prostate cancer specific to men of African ancestry (19).Although some cancer risk factors are well established, the biologic mechanisms through which their impact on cancer risk varies across different populations remain incompletely understood. For example, variations in diet are hypothesized to be the primary driver of the dramatic variations in colorectal cancer incidence rates observed across populations. Recent research has evaluated the impact that different diets have on microbiota composition and function, which in turn affects the production of metabolites that either promote mucosal health or are proinflammatory/neoplastic in the gut. A study that compared Americans with African ancestry (who have a relatively high incidence of colorectal cancer) with rural South Africans (who have a comparatively very low colorectal cancer incidence rate) demonstrated that a typical U.S. diet with high meat and fat intake increases mucosal proliferation rates (a marker of cancer risk) when fed to both populations, whereas typical high-fiber South African diets were associated with low proliferation rates when fed to both groups. This demonstrates that diet can have a profound and fairly immediate impact on the gut microbiome that can either promote or suppress tumors (20).Cancer outcome disparities are well documented for racial and ethnic minorities, and presentation at more advanced stages of cancer explains much of this difference. However, even when controlling for the stage of cancer at diagnosis, the survival disparities persist. What is most concerning is that rather than improving over time, for cancers such as colon cancer, the stage-specific disparities are actually worsening (21). The reason for this growing disparity is not completely clear but involves socioeconomic issues such as education status and the level of insurance and access to medical care. Even in studies that normalize socioeconomic issues (with the limitations cited in the Defining Measures section), disparities that disproportionally affect U.S. minority populations can still be demonstrated for several cancers and may highlight the not-so-well-understood interplay between genetic predisposition and environmental exposure, such as lifestyle and diet, that modifies cancer risk (22, 23). Ultimately, growing postdiagnosis survival disparities are caused by the interplay of system, social, biologic, and environmental factors. Documenting and addressing each of these and their interactions are key to eliminating these disparities. The role of system-level and social determinants in explaining cancer health disparities is best demonstrated by recognizing that disparities vary widely across the United States; some states show almost no disparities, whereas others show striking ones (24). We also know that disparities in treatment of cancer differ and that when treatment differences are accounted for, either through the use of standardized therapies on a clinical trial or through multivariable modeling, cancer-specific survival disparities often disappear. We also have clear examples of successful system-level reform (21, 25, 26). We know, therefore, this is a solvable problem. The key step toward improving care and reducing cancer health disparities requires accurate measurement of meaningful variables, fed back in real time to key stakeholders in the system, followed by meaningful action and continued monitoring to ensure that the action was successful. Determining meaningful measurement across the cancer spectrum may vary by sociocultural factors and require patient and stakeholder input. These system-based practices formed the core of a recent Institute of Medicine report, “Systems Practices for the Care of Socially At-Risk Populations” (27). Systems can be thought of at a macro level, such as state, county, or city governments, all the way down to the individual practice or physician level. Implementation science can inform the best approaches to ensure delivery of high-quality cancer care. Cancers can start as a result of chronic inflammation, and inflammation can modify the behavior of cancer. Biomarkers, such as elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) that can be detected from inflammation-laden cancers, are associated with worse patient outcome and increased metastasis and appear to be more common among African Americans. Microsatellite-unstable (MSI) cancers, which have an overall good prognosis, may be half as common among African Americans compared with whites (28). Both EMAST and MSI have implications for (1) chemotherapeutic response and (2) immunotherapeutic response. In terms of race, these aspects have not been studied. Furthermore, there is much evidence that the microbiome can influence (1) inflammation, (2) response to chemotherapy, and (3) cancer or precancerous lesion formation; also, the microbiome itself can be determined by diet and other factors. These aspects have not been examined with race in mind. Additionally, driver genes may be different within the same type of cancer from patients with different genetic backgrounds, which have implications for correct, definitive therapeutic approaches (29).Most studies that use human specimens to study aspects of cancer and race or ethnicity come from limited individual collections with sparse clinical–epidemiologic information, with rare exception. The exceptions tend to be NCI-funded projects, such as the North Carolina Colon Cancer Study, in which peer review and thoughtful input about how the collection was made with controls, surveys, and linked information to make the collection more meaningful, comprehensive in information, potentially useful for other future studies, and possessed of longevity. However, these types of collections or biorepositories, which include tumor and nontumor specimens, have not been created from diverse samples representative of the U.S. Census population. Current models of health care delivery are highly focused on the use of technology and innovation to improve patient outcomes across disease processes, as demonstrated by the focus on precision medicine in cancer treatment (32–36). Although oncology attempts to embrace this approach, the impact of innovative treatments has been hampered by poor translation of innovation into health care systems and patients from diverse community settings (37, 38). As precision medicine in cancer is accelerated as part of the Beau Biden Cancer Moonshot and other initiatives, the importance of community engagement to ensure that all patients benefit from these advances cannot be overlooked. Cancer health disparities must be taken into consideration in the design, execution, and evaluation of all such programs. Community-engaged research (CER) has been documented as an effective, beneficial method for engaging communities and formulating research that has relevance and impact for both researchers and affected communities (39–42). Involving relevant community stakeholders in research at the planning stages allows for a deeper understanding of community needs, allows researchers to have an iterative method for evaluating research questions in an active realistic milieu, and simultaneously creates a valuable vehicle for active dissemination of the research findings into the communities they are intended to serve. CER offers the potential to improve processes and outcomes in several areas, including care delivery, continuity of care, managing comorbidities, and supportive care (42).Unfortunately, there is a dearth of support for oncology health professionals who choose to work in CER, given its necessity for infrastructure and relationship building, the complex personal interactions with communities and community organizations, and the need to establish long-term benefits to the community after the research project is completed. Importantly, CER requires not only a broad range of expertise across multiple disciplines, but also investigators skilled in a team science approach (43). The benefit of this type of team science has been touted across disciplines; however, its implementation has been limited (44).A lack of workforce diversity has been identified as a barrier to improving access to care for underserved minority groups as well as to advancing research on health disparities (45, 46). Organizations, including ASCO and the American Society of Hematology, have sought to increase workforce diversity in oncology through awards and mentoring programs that expose minorities to in oncology at the medical and In the to Cancer Health Disparities and the American Association for Cancer several programs aimed at the of researchers in cancer and cancer health disparities research. of these types are needed to an oncology workforce that the diversity of the patients it CER not often with most and will require on of the research in both and such an it will remain to create a between CER and the that in cancer are the most important and available to evidence for care and of patients with cancer and individuals at risk for cancer that advanced new approaches from clinical care and diverse oncology the of clinical is to evidence that is both and future must include research questions that consider the multifactorial and multilevel that populations with the cancer This to advance disparities research within the cancer clinical within a new of for in cancer clinical and common for providing trial information have been to for rural patients and patients with lower SES, limited low health and The high and of chronic and of risk factors for chronic such as and must inform to these populations fully in cancer As an example, African Americans a burden of the that from studies, and it is to which could be reasonably as or could be or within the study In addition to those from cancer prevention and treatment also has that populations often are later in the and do not support and rates are key that influence the outcome of clinical cancer studies, those in which minorities have higher disease such as breast, prostate, and cancers In and treatment and rates lower rates exist for those patients who from to and Many such as and to the However, community engagement is to address the and challenges that the clinical CER has been demonstrated to promote building, and the and dissemination of information needed for and long-term As an example, the evaluated the of community health to promote and in and rural populations and that community health can be trained to as research and can be for of and cancer clinical trial and require an of often to be collected at multiple time thought should be given to how best to the of and the study (e.g., and needed to support collection and of specimens from and that to field of cancer health disparities has into a complex science and an field of cancer research. Unfortunately, the to this research has not been and the infrastructure needed to it to the level, can be is The of this which has been by from these four organizations, is to the of advances in this is that this statement will be by both and organizations to inform specific made to improve cancer health disparities eliminating identified disparities in cancer incidence, of care, and recommendations for action have a new in cancer health disparities that has the potential to benefit from across and the in cancer incidence and disparities that affects minorities and the medically it is that in this of cancer research when are being there will be opportunities to this new knowledge to all populations, and cancer health disparities for and future has in a or role for and and as a of the for has research from and has other from the has in a or role for and has research his from and and has and from and has from has in a or role for the and and has research from or other in and has from and has and from for both and an immediate or other in and and has research her from potential of were by the other and and of and of for all aspects of the the of and the for their of this to and

Cancer Research · 84 citationsread the source →

Assessment of Unmet Health-Related Social Needs Among Patients With Mental Illness Enrolled in Medicare Advantage.

Importance: A large body of literature has found associations between unmet health-related social needs (HRSNs) and adverse mental health outcomes. A comparative analysis of the risks associated with HRSNs among patients with varying severity of mental illness and an assessment of how these risks compare with those of individuals without mental illness are needed. Objective: To examine the prevalence and risks of HRSNs among patients with serious and persistent mental illness (SPMI), patients with mental health diagnoses but no serious and persistent mental illness (non-SPMI), and patients with both SPMI and non-SPMI compared with individuals without mental illness. Design, setting, and participants: This retrospective cohort study used data from the Accountable Health Communities HRSN Screening Tool surveys, which target a nationally representative sample of Medicare Advantage members of a large payer (Humana Inc). The surveys were conducted between October 16, 2019, and February 29, 2020. Of the initial 329 008 eligible Medicare Advantage enrollees, 70 273 responded to the survey (21.4% response rate). Of those, 56 081 respondents (79.8%) had complete survey responses and were included in the final analytic sample. Main outcomes and measures: Outcomes of interest included 7 HRSNs (financial strain, food insecurity, housing instability, housing quality, severe loneliness, transportation problems, and utility affordability) based on responses to the survey. The major independent variable was the presence of mental illness up to 12 months preceding the date of survey completion. Codes indicating mental illness listed as the primary, principal, or secondary diagnoses of a patient's inpatient or outpatient medical claims data were identified, and participants were grouped into 4 cohorts: SPMI, non-SPMI, SPMI plus non-SPMI, and no mental illness. Results: Among 56 081 older adults, the mean (SD) age was 71.31 (8.59) years; 32 717 participants (58.3%) were female, and 43 498 (77.6%) were White. A total of 21 644 participants (38.6%) had at least 1 mental illness diagnosis in the past year, 30 262 (54.0%) had an HRSN, and 14 163 (25.3%) had both mental illness and an HRSN. Across all specific HRSNs, the odds of experiencing the respective HRSN was most substantial for those with SPMI plus non-SPMI vs those with only non-SPMI or SPMI. The HRSN with the largest risk differences among the study cohorts was severe loneliness; compared with the cohort without mental illness, the non-SPMI cohort had 2.07 times higher odds (95% CI, 1.84-2.32; P < .001), the SPMI cohort had 3.35 times higher odds (95% CI, 3.03-3.71; P < .001), and the SPMI plus non-SPMI cohort had 5.13 times higher odds (95% CI, 4.68-5.61; P < .001) of severe loneliness. Conclusions and relevance: In this study, the increased risk of having HRSNs associated with SPMI, alone or in combination with non-SPMI, emphasizes the need for more targeted interventions to address social needs in this vulnerable population.

JAMA network open · 11 citationsread the source →

Risk factors for non-suicidal self-injury (NSSI) in adolescents: A meta-analysis.

Background: Non-suicidal self-injury (NSSI) in adolescents is a significant mental health problem around the world. Here, we performed a meta-analysis to systematically delineate the risk factors for NSSI. Method: We searched Medline, Embase, Web of Science and Cochrane for relevant articles and abstracts published prior to 12 November 2021. Pooled odds ratios (ORs) and 95% confident intervals (CIs) were used to assess various risk factors, and publication bias was assessed by Egger's test, the trim and fill method and meta-regression. This study is registered with PROSPERO, CRD42021265885. Results: A total of 25 articles were eventually included in the analysis. Eighty risk factors were identified and classified into 7 categories: mental disorders (ORs, 1·89; 95% CI, 1·60-2·24), bullying (ORs, 1·98; 95% CI, 1·32-2·95), low health literacy (ORs, 2·20; 95% CI, 1·63-2·96), problem behaviours (ORs, 2·36; 95% CI, 2·00-2·77), adverse childhood experiences (ORs, 2·49; 95% CI, 1·85-3.34), physical symptoms (ORs, 2·85; 95% CI, 1·36-5·97) and the female gender (ORs, 2·89; 95% CI, 2·43-3·43). The range of heterogeneity (I2) was from 20·3% to 99·2%. Conclusion: This meta-analysis found that mental disorders, low health literacy, adverse childhood experiences, bullying, problem behaviours, the female gender and physical symptoms appear to be risk factors for NSSI.

EClinicalMedicine · 170 citationsread the source →

The bidirectional associations between state anger and rumination and the role of trait mindfulness.

Rumination is associated with exacerbated angry mood. Angry moods may also trigger rumination. However, research has not empirically tested the bidirectional associations of state rumination and anger, as experience sampling methodology can do. We predicted that state anger and rumination would be bi-directionally associated, both concurrently and over time, even controlling for trait anger and rumination. In addition, because mindfulness is associated with rumination and anger at the bivariate level, we examined the effect of trait mindfulness on the bidirectional association between state rumination and anger. We examined two hypotheses: (i) state rumination mediates the effect of trait mindfulness on state anger; and (ii) trait mindfulness weakens, or moderates, the bidirectional associations between state rumination and anger. In an experience-sampling study, 200 college students reported their current ruminative thinking and angry mood several times a day for 7 days. Mixed model analyses indicated that state anger and rumination predicted each other concurrently. In cross-lagged analyses, previous anger did not uniquely predict current rumination; previous rumination predicted current anger, although the effect was small. In support of our hypothesis, state rumination mediated the association between trait mindfulness and state anger. Additionally, trait mindfulness moderated the concurrent and cross-lagged associations between state rumination and anger, although the results were complex. This study contributes new information about the complex interplay of rumination and anger. Findings also add support to the theory that mindfulness decreases emotional reactivity. Aggr. Behav. 43:342-351, 2017. © 2016 Wiley Periodicals, Inc.

Aggressive behavior · 15 citationsread the source →

Assessing child development scores among minority and Indigenous language versus dominant language speakers: a cross-sectional analysis of national Multiple Indicator Cluster Surveys.

Background: Multiple studies have highlighted the inequities minority and Indigenous children face when accessing health care. Health and wellbeing are positively impacted when Indigenous children are educated and receive care in their maternal language. However, less is known about the association between minority or Indigenous language use and child development risks and outcomes. In this study, we provide global estimates of development risks and assess the associations between minority or Indigenous language status and early child development using the ten-item Early Child Development Index (ECDI), a tool widely used for global population assessments in children aged 3-4 years. Methods: We did a secondary analysis of cross-sectional data from 65 UNICEF Multiple Indicator Cluster Surveys (MICS) containing the ECDI from 2009-19 (waves 4-6). We included individual-level data for children aged 2-4 years (23-60 months) from datasets with ECDI modules, for surveys that captured the language of the respondent, interview, or head of household. The Expanded Graded Intergenerational Disruption Scale was used to classify household languages as dominant versus minority or Indigenous at the country level. Our primary outcome was on-track overall development, defined per UNICEF's guidelines as development being on track for at least three of the four ECDI domains (literacy-numeracy, learning, physical, and socioemotional). We performed logistic regression of pooled, weighted ECDI scores, aggregated by language status and adjusting for the covariables of child sex, child nutritional status (stunting), household wealth, maternal education, developmental support by an adult caregiver, and country-level early child education proportion. Regression analyses were done for all children aged 3-4 years with ECDI results, and separately for children with functional disabilities and ECDI results. Findings: 65 MICS datasets were included. 186 393 children aged 3-4 years had ECDI and language data, corresponding to an estimated represented population of 34 714 992 individuals. Estimated prevalence of on-track overall development as measured by ECDI scores was 65·7% (95% CI 64·2-67·2) for children from a minority or Indigenous language-speaking household, and 76·6% (75·7-77·4) for those from a dominant language-speaking household. After adjustment, dominant language status was associated with increased odds of on-track overall development (adjusted OR 1·54, 95% CI 1·40-1·71), which appeared to be largely driven by significantly increased odds of on-track development in the literacy-numeracy and socioemotional domains. For the represented population aged 2-4 years (n=11 465 601), the estimated prevalence of family-reported functional disability was 3·6% (95% CI 3·0-4·4). For the represented population aged 3-4 years with a functional disability (n=292 691), language status was not associated with on-track overall development (adjusted OR 1·02, 95% CI 0·43-2·45). Interpretation: In a global dataset, children speaking a minority or Indigenous language were less likely to have on-track ECDI scores than those speaking a dominant language. Given the strong positive benefits of speaking an Indigenous language on the health and development of Indigenous children, this disparity is likely to reflect the sociolinguistic marginalisation faced by speakers of minority or Indigenous languages as well as differences in the performance of ECDI in these languages. Global efforts should consider performance of measures and monitor developmental data disaggregated by language status to stimulate efforts to address this disparity. Funding: None. Translations: For the Spanish, Kaqchikel and K'iche' translations of the abstract see Supplementary Materials section.

The Lancet. Global health · 2 citationsread the source →

Outcomes in people with eating disorders: a transdiagnostic and disorder-specific systematic review, meta-analysis and multivariable meta-regression analysis.

Eating disorders (EDs) are known to be associated with high mortality and often chronic and severe course, but a recent comprehensive systematic review of their outcomes is currently missing. In the present systematic review and meta-analysis, we examined cohort studies and clinical trials published between 1980 and 2021 that reported, for DSM/ICD-defined EDs, overall ED outcomes (i.e., recovery, improvement and relapse, all-cause and ED-related hospitalization, and chronicity); the same outcomes related to purging, binge eating and body weight status; as well as mortality. We included 415 studies (N=88,372, mean age: 25.7±6.9 years, females: 72.4%, mean follow-up: 38.3±76.5 months), conducted in persons with anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), other specified feeding and eating disorders (OSFED), and/or mixed EDs, from all continents except Africa. In all EDs pooled together, overall recovery occurred in 46% of patients (95% CI: 44-49, n=283, mean follow-up: 44.9±62.8 months, no significant ED-group difference). The recovery rate was 42% at <2 years, 43% at 2 to <4 years, 54% at 4 to <6 years, 59% at 6 to <8 years, 64% at 8 to <10 years, and 67% at ≥10 years. Overall chronicity occurred in 25% of patients (95% CI: 23-29, n=170, mean follow-up: 59.3±71.2 months, no significant ED-group difference). The chronicity rate was 33% at <2 years, 40% at 2 to <4 years, 23% at 4 to <6 years, 25% at 6 to <8 years, 12% at 8 to <10 years, and 18% at ≥10 years. Mortality occurred in 0.4% of patients (95% CI: 0.2-0.7, n=214, mean follow-up: 72.2±117.7 months, no significant ED-group difference). Considering observational studies, the mortality rate was 5.2 deaths/1,000 person-years (95% CI: 4.4-6.1, n=167, mean follow-up: 88.7±120.5 months; significant difference among EDs: p<0.01, range: from 8.2 for mixed ED to 3.4 for BN). Hospitalization occurred in 26% of patients (95% CI: 18-36, n=18, mean follow-up: 43.2±41.6 months; significant difference among EDs: p<0.001, range: from 32% for AN to 4% for BN). Regarding diagnostic migration, 8% of patients with AN migrated to BN and 16% to OSFED; 2% of patients with BN migrated to AN, 5% to BED, and 19% to OSFED; 9% of patients with BED migrated to BN and 19% to OSFED; 7% of patients with OSFED migrated to AN and 10% to BN. Children/adolescents had more favorable outcomes across and within EDs than adults. Self-injurious behaviors were associated with lower recovery rates in pooled EDs. A higher socio-demographic index moderated lower recovery and higher chronicity in AN across countries. Specific treatments associated with higher recovery rates were family-based therapy, cognitive-behavioral therapy (CBT), psychodynamic therapy, and nutritional interventions for AN; self-help, CBT, dialectical behavioral therapy (DBT), psychodynamic therapy, nutritional and pharmacological treatments for BN; CBT, nutritional and pharmacological interventions, and DBT for BED; and CBT and psychodynamic therapy for OSFED. In AN, pharmacological treatment was associated with lower recovery, and waiting list with higher mortality. These results should inform future research, clinical practice and health service organization for persons with EDs.

World psychiatry : official journal of the World Psychiatric Association (WPA) · 148 citationsread the source →