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حَدَّثَنَا أَبُو الْيَمَانِ، أَخْبَرَنَا شُعَيْبٌ، حَدَّثَنَا أَبُو الزِّنَادِ، عَنْ عَبْدِ الرَّحْمَنِ، عَنْ أَبِي هُرَيْرَةَ، أَنَّ رَسُولَ اللَّهِ صلى الله عليه وسلم قَالَ ‏ "‏ لاَ تَقُومُ السَّاعَةُ حَتَّى تَقْتَتِلَ فِئَتَانِ عَظِيمَتَانِ، يَكُونُ بَيْنَهُمَا مَقْتَلَةٌ عَظِيمَةٌ، دَعْوَتُهُمَا وَاحِدَةٌ، وَحَتَّى يُبْعَثَ دَجَّالُونَ كَذَّابُونَ، قَرِيبٌ مِنْ ثَلاَثِينَ، كُلُّهُمْ يَزْعُمُ أَنَّهُ رَسُولُ اللَّهِ، وَحَتَّى يُقْبَضَ الْعِلْمُ، وَتَكْثُرَ الزَّلاَزِلُ، وَيَتَقَارَبَ الزَّمَانُ، وَتَظْهَرَ الْفِتَنُ، وَيَكْثُرَ الْهَرْجُ وَهْوَ الْقَتْلُ، وَحَتَّى يَكْثُرَ فِيكُمُ الْمَالُ فَيَفِيضَ، حَتَّى يُهِمَّ رَبَّ الْمَالِ مَنْ يَقْبَلُ صَدَقَتَهُ، وَحَتَّى يَعْرِضَهُ فَيَقُولَ الَّذِي يَعْرِضُهُ عَلَيْهِ لاَ أَرَبَ لِي بِهِ‏.‏ وَحَتَّى يَتَطَاوَلَ النَّاسُ فِي الْبُنْيَانِ، وَحَتَّى يَمُرَّ الرَّجُلُ بِقَبْرِ الرَّجُلِ فَيَقُولُ يَا لَيْتَنِي مَكَانَهُ‏.‏ وَحَتَّى تَطْلُعَ الشَّمْسُ مِنْ مَغْرِبِهَا، فَإِذَا طَلَعَتْ وَرَآهَا النَّاسُ ـ يَعْنِي ـ آمَنُوا أَجْمَعُونَ، فَذَلِكَ حِينَ لاَ يَنْفَعُ نَفْسًا إِيمَانُهَا لَمْ تَكُنْ آمَنَتْ مِنْ قَبْلُ، أَوْ كَسَبَتْ فِي إِيمَانِهَا خَيْرًا، وَلَتَقُومَنَّ السَّاعَةُ وَقَدْ نَشَرَ الرَّجُلاَنِ ثَوْبَهُمَا بَيْنَهُمَا، فَلاَ يَتَبَايَعَانِهِ وَلاَ يَطْوِيَانِهِ، وَلَتَقُومَنَّ السَّاعَةُ وَقَدِ انْصَرَفَ الرَّجُلُ بِلَبَنِ لِقْحَتِهِ فَلاَ يَطْعَمُهُ، وَلَتَقُومَنَّ السَّاعَةُ وَهْوَ يُلِيطُ حَوْضَهُ فَلاَ يَسْقِي فِيهِ، وَلَتَقُومَنَّ السَّاعَةُ وَقَدْ رَفَعَ أُكْلَتَهُ إِلَى فِيهِ فَلاَ يَطْعَمُهَا ‏"‏‏.‏

Narrated Abu Huraira:Allah's Messenger (ﷺ) said, "The Hour will not be established (1) till two big groups fight each other whereupon there will be a great number of casualties on both sides and they will be following one and the same religious doctrine, (2) till about thirty Dajjals (liars) appear, and each one of them will claim that he is Allah's Messenger (ﷺ), (3) till the religious knowledge is taken away (by the death of Religious scholars) (4) earthquakes will increase in number (5) time will pass quickly, (6) afflictions will appear, (7) Al-Harj, (i.e., killing) will increase, (8) till wealth will be in abundance ---- so abundant that a wealthy person will worry lest nobody should accept his Zakat, and whenever he will present it to someone, that person (to whom it will be offered) will say, 'I am not in need of it, (9) till the people compete with one another in constructing high buildings, (10) till a man when passing by a grave of someone will say, 'Would that I were in his place (11) and till the sun rises from the West. So when the sun will rise and the people will see it (rising from the West) they will all believe (embrace Islam) but that will be the time when: (As Allah said,) 'No good will it do to a soul to believe then, if it believed not before, nor earned good (by deeds of righteousness) through its Faith.' (6.158) And the Hour will be established while two men spreading a garment in front of them but they will not be able to sell it, nor fold it up; and the Hour will be established when a man has milked his she-camel and has taken away the milk but he will not be able to drink it; and the Hour will be established before a man repairing a tank (for his livestock) is able to water (his animals) in it; and the Hour will be established when a person has raised a morsel (of food) to his mouth but will not be able to eat it

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Long-term outcomes of childhood sexual abuse: an umbrella review.

Background: Although many meta-analyses have examined the association between childhood sexual abuse and subsequent outcomes, the scope, validity, and quality of this evidence has not been comprehensively assessed. We aimed to systematically review existing meta-analyses on a wide range of long-term psychiatric, psychosocial, and physical health outcomes of childhood sexual abuse, and evaluate the quality of the literature. Methods: In this umbrella review, we searched four databases (PsycINFO, PubMed, Cumulative Index to Nursing and Allied Health Literature, and Global Health) from inception to Dec 31, 2018, to identify meta-analyses of observational studies that examined the association between childhood sexual abuse (before 18 years of age) and long-term consequences (after 18 years). We compared odds ratios (ORs) across different outcomes. We also examined measures of quality, including heterogeneity between studies and evidence for publication bias. This study is registered with PROSPERO, CRD42016049701. Findings: We identified 19 meta-analyses that included 559 primary studies, covering 28 outcomes in 4 089 547 participants. Childhood sexual abuse was associated with 26 of 28 specific outcomes: specifically, six of eight adult psychiatric diagnoses (ORs ranged from 2·2 [95% CI 1·8-2·8] to 3·3 [2·2-4·8]), all studied negative psychosocial outcomes (ORs ranged from 1·2 [1·1-1·4] to 3·4 [2·3-4·8]), and all physical health conditions (ORs ranged from 1·4 [1·3-1·6] to 1·9 [1·4-2·8]). Strongest psychiatric associations with childhood sexual abuse were reported for conversion disorder (OR 3·3 [95% CI 2·2-4·8]), borderline personality disorder (2·9 [2·5-3·3]), anxiety (2·7 [2·5-2·8]), and depression (2·7 [2·4-3·0]). The systematic reviews for two psychiatric outcomes (post-traumatic stress disorder and schizophrenia) and one psychosocial outcome (substance misuse) met high quality standards. Quality was low for meta-analyses on borderline personality disorder and anxiety, and moderate for conversion disorder. Assuming causality, population attributable risk fractions for outcomes ranged from 1·7% (95% CI 0·7-3·3) for unprotected sexual intercourse to 14·4% (8·8-19·9) for conversion disorder. Interpretation: Although childhood sexual abuse was associated with a wide range of psychosocial and health outcomes, systematic reviews on only two psychiatric disorders (post-traumatic stress disorder and schizophrenia) and one psychosocial outcome (substance misuse) were of a high quality. Whether services should prioritise interventions that mitigate developing certain psychiatric disorders following childhood abuse requires further review. Higher-quality meta-analyses for specific outcomes and more empirical studies on the developmental pathways from childhood sexual abuse to later outcomes are necessary. Funding: Wellcome Trust.

The lancet. Psychiatry · systematic review · 459 citationsread the source →

Effects of digital cognitive behavioural therapy for insomnia on insomnia severity: a large-scale randomised controlled trial.

Background: Although several large-scale randomised controlled trials have shown the efficacy of digital cognitive behavioural therapy for insomnia (dCBT-I), there is a need to validate widespread dissemination of dCBT-I using recommended key outcomes for insomnia. We investigated the effect of a fully automated dCBT-I programme on insomnia severity, sleep-wake patterns, sleep medication use, and daytime impairment. Methods: We did a parallel-group superiority randomised controlled trial comparing dCBT-I with online patient education about sleep. The interventions were available through a free-to-access website, publicised throughout Norway, which incorporated automated screening, informed consent, and randomisation procedures, as well as outcome assessments. Adults (age ≥18 years) who had regular internet access and scored 12 or higher on the Insomnia Severity Index (ISI) were eligible for inclusion, and were allocated (1:1) to receive dCBT-I (consisting of six core interactive sessions to be completed over 9 weeks) or patient education (control group). Participants were masked to group assignment and had no contact with researchers during the intervention period. The primary outcome was the change in ISI score from baseline to 9-week follow-up, assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02558647) and is ongoing, with 2-year follow-up assessments planned. Findings: Between Feb 26, 2016, and July 1, 2018, 5349 individuals commenced the online screening process, of which 1497 were ineligible or declined to participate, 2131 discontinued the screening process, and 1721 were randomly allocated (868 to receive dCBT-I and 853 to receive patient education). At 9-week follow-up, 584 (67%) participants in the dCBT-I group and 534 (63%) in the patient education group completed the ISI assessment. The latent growth model showed that participants in the dCBT-I group had a significantly greater reduction in ISI scores from baseline (mean score 19·2 [SD 3·9]) to 9-week follow-up (10·4 [6·2]) than those in the patient education group (from 19·6 [4·0] to 15·2 [5·3]; estimated mean difference -4·7 (95% CI -5·4 to -4·1; Cohen's d -1·21; p<0·001). Compared with patient education, the number needed to treat with dCBT-I was 2·7 (95% CI 2·4 to 3·2) for treatment response (ISI score reduction ≥8) and 3·2 (2·8 to 3·8) for insomnia remission (ISI score <8). No adverse events were reported to the trial team. Interpretation: dCBT-I is effective in reducing the severity of symptoms associated with the insomnia disorder. These findings support the widespread dissemination of dCBT-I. Future research is needed to identify the moderators of response and to improve targeting. Funding: Norwegian Research Council; Liaison Committee for Education, Research and Innovation in Central Norway.

The Lancet. Digital health · randomised controlled trial · 95 citationsread the source →

Effectiveness of Family Integrated Care in neonatal intensive care units on infant and parent outcomes: a multicentre, multinational, cluster-randomised controlled trial.

Background: Despite evidence suggesting that parent involvement was beneficial for infant and parent outcomes, the Family Integrated Care (FICare) programme was one of the first pragmatic approaches to enable parents to become primary caregivers in the neonatal intensive care unit (NICU). We aimed to analyse the effect of FICare on infant and parent outcomes, safety, and resource use. Methods: In this multicentre, cluster-randomised controlled trial, we stratified 26 tertiary NICUs from Canada, Australia, and New Zealand by country and size, and assigned them, using a computer-generated random allocation sequence, to provide FICare or standard NICU care. Eligible infants were born at 33 weeks' gestation or earlier, and had no or low-level respiratory support; parents gave written informed consent for enrolment. To be eligible, parents in the FICare group had to commit to be present for at least 6 h a day, attend educational sessions, and actively care for their infant. The primary outcome, analysed at the individual level, was infant weight gain at day 21 after enrolment. Secondary outcomes were weight gain velocity, high frequency breastfeeding (≥6 times a day) at hospital discharge, parental stress and anxiety at enrolment and day 21, NICU mortality and major neonatal morbidities, safety, and resource use (including duration of oxygen therapy and hospital stay). This trial is registered with ClinicalTrials.gov, number NCT01852695. Findings: From Oct 1, 2012, 26 sites were randomly assigned to provide FICare (n=14) or standard care (n=12). One site assigned to FICare discontinued because of poor site enrolment. Parents and infants were enrolled between April 1, 2013, and Aug 31, 2015, with 895 infants being eligible in the FICare group and 891 in the standard care group. At day 21, weight gain was greater in the FICare group than in the standard care group (mean change in Z scores -0·071 [SD 0·42] vs -0·155 [0·42]; p<0·0002). Average daily weight gain was significantly higher in infants receiving FICare than those receiving standard care (mean daily weight gain 26·7 g [SD 9·4] vs 24·8 g [9·5]; p<0·0001). The high-frequency exclusive breastmilk feeding rate at discharge was higher for infants in the FICare group (279 [70%] of 396) than those in the standard care group (394 [63%] of 624; p=0·016). At day 21, parents in the FICare group had lower mean stress scores than did parents in the standard care group (2·3 [SD 0·8] vs 2·5 [0·8]; p<0·00043), and lower mean anxiety scores (70·8 [20·1] vs 74·2 [19·9]; p=0·0045). There were no significant differences between groups in the rates of the secondary outcomes of mortality, major morbidity, duration of oxygen therapy, and duration of hospital stay. Although the safety assessment was not completed, there were no adverse events. Interpretation: FICare improved infant weight gain, decreased parent stress and anxiety, and increased high-frequency exclusive breastmilk feeding at discharge, which together suggest that FICare is an important advancement in neonatal care. Further research is required to examine if these results translate into better long-term outcomes for families. Funding: Canadian Institutes of Health Research Partnerships for Health System Improvement, and Ontario Ministry of Health and Long-Term Care.

The Lancet. Child & adolescent health · randomised controlled trial · 374 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 →

A systematic review of the associations between biodiversity and children's mental health and wellbeing.

There is a growing interest in how exposure to biodiversity influences mental health and wellbeing; however, few studies have focused on children. The aim of this review was to identify studies that used components of biodiversity and children's health outcomes to assess if there were any themes that could be used to inform urban design and understand the mechanisms behind associations. We used a PROSPERO registered protocol to identify eligible studies following pre-defined inclusion criteria. After searching five databases, 25 studies were included in the review. From these articles we extracted data on the biodiversity exposure and mental health and wellbeing outcomes. Five categories of biodiversity exposure were identified, including species diversity (n = 1; 4%), functional diversity (n = 6; 26%), ecological community (n = 9; 36%), green space metrics (n = 4; 16%), and high-level classifications (n = 6; 24%). Children's health and wellbeing were tabulated into seven categories: play (n = 10; 40%), wellbeing (n = 6; 24%), mental health and cognitive functioning (n = 5; 20%), attention deficit hyperactivity disorder (ADHD)-related behaviours (n = 4; 16%), preferences for nature (n = 3; 12%), academic achievement (n = 2; 8%), and restoration (n = 2; 8%). The high heterogeneity of biodiversity and health measures reduced our ability to identify relationships across studies and formally test for an exposure-dose response. Future research that uses standardised and transferable biodiversity measurements at multiple scales, has stronger reporting rigour, greater consideration of potential modifiers, and increased representation of studies from the Majority World are essential for building a stronger evidence base to deliver child-centred biodiverse landscapes.

Environmental research · systematic review · 2 citationsread the source →

Effect of a high-fat Mediterranean diet on bodyweight and waist circumference: a prespecified secondary outcomes analysis of the PREDIMED randomised controlled trial.

Background: Because of the high density of fat, high-fat diets are perceived as likely to lead to increased bodyweight, hence health-care providers are reluctant to recommend them to overweight or obese individuals. We assessed the long-term effects of ad libitum, high-fat, high-vegetable-fat Mediterranean diets on bodyweight and waist circumference in older people at risk of cardiovascular disease, most of whom were overweight or obese. Methods: PREDIMED was a 5 year parallel-group, multicentre, randomised, controlled clinical trial done in primary care centres affiliated to 11 hospitals in Spain. 7447 asymptomatic men (aged 55-80 years) and women (aged 60-80 years) who had type 2 diabetes or three or more cardiovascular risk factors were randomly assigned (1:1:1) with a computer-generated number sequence to one of three interventions: Mediterranean diet supplemented with extra-virgin olive oil (n=2543); Mediterranean diet supplemented with nuts (n=2454); or a control diet (advice to reduce dietary fat; n=2450). Energy restriction was not advised, nor was physical activity promoted. In 2016, we reported the 5 year changes in bodyweight and waist circumference, but because of a subsequently identified protocol deviation (including enrolment of household members without randomisation, assignment to a study group without randomisation of some participants at one of 11 study sites, and apparent inconsistent use of randomisation tables at another site; 866 [11·6%] participants were affected in total), we have withdrawn our previously published report and now report revised effect estimates based on reanalyses that do not rely exclusively on the assumption that all the participants were randomly assigned. In this analysis of the trial, we measured bodyweight and waist circumference at baseline and yearly for 5 years in the intention-to-treat population. The PREDIMED trial is registered with ISRCTN.com, number ISRCTN35739639. Findings: After a median 4·8 years (IQR 2·8-5·8) of follow-up, participants in all three groups had marginally reduced bodyweight and increased waist circumference. After multivariable adjustment, including adjustment for propensity scores and use of robust variance estimators, the difference in 5 year changes in bodyweight in the Mediterranean diet with olive oil group was -0·410 kg (95% CI -0·830 to 0·010; p=0·056) and in the nut group was -0·016 kg (-0·453 to 0·421; p=0·942), compared with the control group. The adjusted difference in 5 year changes in waist circumference was -0·466 cm (-1·109 to 0·176; p=0·154) in the Mediterranean diet with olive oil group and -0·923 cm (-1·604 to -0·241; p=0·008) in the nut group, compared with the control group. Interpretation: A long-term intervention with an unrestricted-calorie, high-vegetable-fat Mediterranean diet was associated with no significant difference in bodyweight and some evidence of less gain in central adiposity compared with a control diet. These results lend support to advice not restricting intake of healthy fats for bodyweight maintenance. Funding: Spanish Government, CIBERobn, Instituto de Salud Carlos III, Hojiblanca, Patrimonio Comunal Olivarero, California Walnut Commission, Borges SA, and Morella Nuts.

The lancet. Diabetes & endocrinology · randomised controlled trial · 101 citationsread the source →

Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.

Background: The mental disorders included in the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 were depressive disorders, anxiety disorders, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, eating disorders, idiopathic developmental intellectual disability, and a residual category of other mental disorders. We aimed to measure the global, regional, and national prevalence, disability-adjusted life-years (DALYS), years lived with disability (YLDs), and years of life lost (YLLs) for mental disorders from 1990 to 2019. Methods: In this study, we assessed prevalence and burden estimates from GBD 2019 for 12 mental disorders, males and females, 23 age groups, 204 countries and territories, between 1990 and 2019. DALYs were estimated as the sum of YLDs and YLLs to premature mortality. We systematically reviewed PsycINFO, Embase, PubMed, and the Global Health Data Exchange to obtain data on prevalence, incidence, remission, duration, severity, and excess mortality for each mental disorder. These data informed a Bayesian meta-regression analysis to estimate prevalence by disorder, age, sex, year, and location. Prevalence was multiplied by corresponding disability weights to estimate YLDs. Cause-specific deaths were compiled from mortality surveillance databases. The Cause of Death Ensemble modelling strategy was used to estimate death rate by age, sex, year, and location. The death rates were multiplied by the years of life expected to be remaining at death based on a normative life expectancy to estimate YLLs. Deaths and YLLs could be calculated only for anorexia nervosa and bulimia nervosa, since these were the only mental disorders identified as underlying causes of death in GBD 2019. Findings: Between 1990 and 2019, the global number of DALYs due to mental disorders increased from 80·8 million (95% uncertainty interval [UI] 59·5-105·9) to 125·3 million (93·0-163·2), and the proportion of global DALYs attributed to mental disorders increased from 3·1% (95% UI 2·4-3·9) to 4·9% (3·9-6·1). Age-standardised DALY rates remained largely consistent between 1990 (1581·2 DALYs [1170·9-2061·4] per 100 000 people) and 2019 (1566·2 DALYs [1160·1-2042·8] per 100 000 people). YLDs contributed to most of the mental disorder burden, with 125·3 million YLDs (95% UI 93·0-163·2; 14·6% [12·2-16·8] of global YLDs) in 2019 attributable to mental disorders. Eating disorders accounted for 17 361·5 YLLs (95% UI 15 518·5-21 459·8). Globally, the age-standardised DALY rate for mental disorders was 1426·5 (95% UI 1056·4-1869·5) per 100 000 population among males and 1703·3 (1261·5-2237·8) per 100 000 population among females. Age-standardised DALY rates were highest in Australasia, Tropical Latin America, and high-income North America. Interpretation: GBD 2019 showed that mental disorders remained among the top ten leading causes of burden worldwide, with no evidence of global reduction in the burden since 1990. The estimated YLLs for mental disorders were extremely low and do not reflect premature mortality in individuals with mental disorders. Research to establish causal pathways between mental disorders and other fatal health outcomes is recommended so that this may be addressed within the GBD study. To reduce the burden of mental disorders, coordinated delivery of effective prevention and treatment programmes by governments and the global health community is imperative. Funding: Bill & Melinda Gates Foundation, Australian National Health and Medical Research Council, Queensland Department of Health, Australia.

The lancet. Psychiatry · systematic review · 4002 citationsread the source →

The global burden of perinatal common mental health disorders and substance use among migrant women: a systematic review and meta-analysis.

Background: There are one billion migrants globally, of whom 82 million are forced migrants. Pregnant migrants face pre-migration stressors such as conflict, transit stressors including poverty, and post-migration stressors including navigating the immigration system; these stressors can make them vulnerable to mental illness. We aimed to assess the global prevalence of and risk factors for perinatal mental health disorders or substance use among women who are migrants. Methods: In this systematic review and meta-analysis, we searched OVID MEDLINE, Embase, PsycINFO, CENTRAL, Global Health, Scopus, and Web of Science for studies published from database inception until July 8, 2022. Cohort, cross-sectional, and interventional studies with prevalence data for any mental illness in pregnancy or the postnatal period (ie, up to a year after delivery) or substance use in pregnancy were included. The primary outcome was the prevalence of perinatal common mental health disorders among women who are migrants, globally. Data for study quality and risk factors were also extracted. A random-effects meta-analysis was used to calculate pooled prevalence estimates, when appropriate. Sensitivity analyses were conducted according to study quality, sample representativeness, and method of outcome assessment. Risk factor data were synthesised narratively. This study is registered with PROSPERO, CRD42021226291. Findings: 18 650 studies were retrieved, of which 135 studies comprising data from 621 995 participants met the inclusion criteria. 123 (91%) of 135 studies were conducted in high-income host countries. Five (4%) of 135 studies were interventional, 40 (30%) were cohort, and 90 (66%) were cross-sectional. The most common regions of origin of participants were South America, the Middle East, and north Africa. Only 26 studies presented disaggregated data for forced migrants or economic migrants. The pooled prevalence of perinatal depressive disorders was 24·2% (range 0·5-95·5%; I2 98·8%; τ2 0·01) among all women who are migrants, 32·5% (1·5-81·6; 98·7%; 0·01) among forced migrants, and 13·7% (4·7-35·1; 91·5%; 0·01) among economic migrants (p<0·001). The pooled prevalence of perinatal anxiety disorders was 19·6% (range 1·2-53·1; I2 96·8%; τ2 0·01) among all migrants. The pooled prevalence of perinatal post-traumatic stress disorder (PTSD) among all migrant women was 8·9% (range 3·2-33·3; I2 97·4%; τ2 0·18). The pooled prevalence of perinatal PTSD among forced migrants was 17·1% (range 6·5-44·3; I2 96·6%; τ2 0·32). Key risk factors for perinatal depression were being a recently arrived immigrant (ie, approximately within the past year), having poor social support, and having a poor relationship with one's partner. Interpretation: One in four women who are migrants and who are pregnant or post partum experience perinatal depression, one in five perinatal anxiety, and one in 11 perinatal PTSD. The burden of perinatal mental illness appears higher among women who are forced migrants compared with women who are economic migrants. To our knowledge, we have provided the first pooled estimate of perinatal depression and PTSD among women who are forced migrants. Interpreting the prevalence estimate should be observed with caution due to the very wide range found within the included studies. Additionally, 66% of studies were cross-sectional representing low quality evidence. These findings highlight the need for community-based routine perinatal mental health screening for migrant communities, and access to interventions that are culturally sensitive, particularly for forced migrants who might experience a higher burden of disease than economic migrants. Funding: UK National Institute for Health Research (NIHR); March of Dimes European Preterm Birth Research Centre, Imperial College; Imperial College NIHR Biomedical Research Centre; and Nuffield Department of Population Health, University of Oxford.

The Lancet. Public health · meta-analysis · 63 citationsread the source →

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

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

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

Molecular Conformations of Di-, Tri-, and Tetra-α-(2→8)-Linked Sialic Acid from NMR Spectroscopy and MD Simulations.

By using molecular dynamics simulations with an efficient enhanced sampling technique and in combination with nuclear magnetic resonance (NMR) spectroscopy quantitative structural information on α -2,8-linked sialic acids is presented. We used a bottom-up approach to obtain a set of larger ensembles for tetra- and deca-sialic acid from model dimer and trimer systems that are in agreement with the available J-coupling constants and nuclear Overhauser effects. The molecular dynamic (MD) simulations with enhanced sampling are used to validate the force field used in this study for its further use. This empowered us to couple NMR observables in the MD framework via J-coupling and distance restraining simulations to obtain conformations that are supported by experimental data. We used these conformations in thermodynamic integration and one-step perturbation simulations to calculate the free-energy of suggested helical conformations. This study brings most of the available NMR experiments together and supplies information to resolve the conflict on the structures of poly- α -2,8-linked sialic acid.

International journal of molecular sciences · 10 citationsread the source →

5-year mental health and eating pattern outcomes following bariatric surgery in adolescents: a prospective cohort study.

Background: Mental health problems are prevalent among adolescents with severe obesity, but long-term mental health outcomes after adolescent bariatric surgery are not well known. We aimed to assess mental health outcomes over 5 years of follow-up after Roux-en-Y gastric bypass surgery in adolescents who participated in the Adolescent Morbid Obesity Surgery (AMOS) study. Methods: This was a non-randomised matched-control study in adolescents aged 13-18 years who had a BMI of 40 kg/m2 or higher, or 35 kg/m2 or higher in addition to obesity-related comorbidity; who had previously undergone failed comprehensive conservative treatment; and were of pubertal Tanner stage III or higher, with height growth velocity beyond peak. A contemporary control group, matched for BMI, age, and sex, who underwent conventional obesity treatment, was obtained from the Swedish Childhood Obesity Treatment Register. Data on dispensed psychiatric drugs and specialist treatment for mental disorders were retrieved from national registers with complete coverage. In the surgical group only, questionnaires were used to assess self-esteem (Rosenberg Self-Esteem [RSE] score), mood (Mood Adjective Checklist [MACL]), and eating patterns (Binge Eating Scale [BES] and Three-Factor Eating Questionnaire-R21 [TFEQ]). This study is registered with ClinicalTrials.gov (NCT00289705). Findings: Between April 10, 2006, and May 20, 2009, 81 adolescents (53 [65%] female) underwent Roux-en-Y gastric bypass surgery, and 80 control participants received conventional treatment. The proportion of participants prescribed psychiatric drugs did not differ between groups in the years before study inclusion (pre-baseline; absolute risk difference 5% [95% CI -7 to 16], p=0·4263) or after intervention (10% [-6 to 24], p=0·2175). Treatment for mental and behavioural disorders did not differ between groups before baseline (2% [-10 to 14], p=0·7135); however, adolescents in the surgical group had more specialised psychiatric treatment in the 5 years after obesity treatment than did the control group (15% [1 to 28], p=0·0410). There were few patients who discontinued psychiatric treatment post-surgery (three [4%] receiving psychiatric drug treatment and six [7%] receiving specialised care for a mental disorder before surgery). In the surgical group, self-esteem (RSE score) was improved after 5 years (mixed model mean 21·6 [95% CI 19·9 to 23·4]) relative to baseline (18·9 [17·4 to 20·4], p=0·0059), but overall mood (MACL score) was not (2·8 [2·7 to 2·9] at 5 years vs 2·7 [2·6 to 2·8] at baseline, p=0·0737). Binge eating was improved at 5 years (9·3 [7·4 to 11·2]) relative to baseline (15·0 [13·5 to 16·5], p<0·0001). Relative changes in BMI were not associated with the presence or absence of binge eating at baseline. Interpretation: Mental health problems persist in adolescents 5 years after bariatric surgery despite substantial weight loss. Although bariatric surgery can improve many aspects of health, alleviation of mental health problems should not be expected, and a multidisciplinary bariatric team should offer long-term mental health support after surgery. Funding: Swedish Research Council, VINNOVA, Västra Götalandsregionen, ALF VG-region, Region Stockholm, Swedish Child Diabetes Foundation, Swedish Heart and Lung Foundation, Tore Nilsson's Foundation, SUS Foundations and Donations, Capio Research Foundation, and Mary von Sydow's Foundation.

The Lancet. Child & adolescent health · 44 citationsread the source →

Early Time-Restricted Feeding Improves 24-Hour Glucose Levels and Affects Markers of the Circadian Clock, Aging, and Autophagy in Humans.

Time-restricted feeding (TRF) is a form of intermittent fasting that involves having a longer daily fasting period. Preliminary studies report that TRF improves cardiometabolic health in rodents and humans. Here, we performed the first study to determine how TRF affects gene expression, circulating hormones, and diurnal patterns in cardiometabolic risk factors in humans. Eleven overweight adults participated in a 4-day randomized crossover study where they ate between 8 am and 2 pm (early TRF (eTRF)) and between 8 am and 8 pm (control schedule). Participants underwent continuous glucose monitoring, and blood was drawn to assess cardiometabolic risk factors, hormones, and gene expression in whole blood cells. Relative to the control schedule, eTRF decreased mean 24-hour glucose levels by 4 ± 1 mg/dl (p = 0.0003) and glycemic excursions by 12 ± 3 mg/dl (p = 0.001). In the morning before breakfast, eTRF increased ketones, cholesterol, and the expression of the stress response and aging gene SIRT1 and the autophagy gene LC3A (all p < 0.04), while in the evening, it tended to increase brain-derived neurotropic factor (BNDF; p = 0.10) and also increased the expression of MTOR (p = 0.007), a major nutrient-sensing protein that regulates cell growth. eTRF also altered the diurnal patterns in cortisol and the expression of several circadian clock genes (p < 0.05). eTRF improves 24-hour glucose levels, alters lipid metabolism and circadian clock gene expression, and may also increase autophagy and have anti-aging effects in humans.

Nutrients · randomised controlled trial · 493 citationsread the source →

Well-Being Outcomes of Health Care Workers After a 5-Hour Continuing Education Intervention: The WELL-B Randomized Clinical Trial.

Importance: Compromised well-being in health care workers (HCWs) is detrimental to the workforce, organizations, and patients. Objective: To test the effectiveness of Well-Being Essentials for Learning Life-Balance (WELL-B), a web-based continuing education program to deliver brief, evidence-based, reflective, psychological interventions to improve 4 dimensions of HCW well-being (ie, emotional exhaustion, emotional thriving, emotional recovery, and work-life integration). Design, setting, and participants: A randomized clinical trial (RCT) of US inpatient and outpatient HCWs randomized 1:1 was conducted from January 3 through May 31, 2023, using a web-based intervention. Cohort 1 received 5 hours of WELL-B over 8 days; cohort 2 acted as the control group and received WELL-B after the end of the RCT. Eligibility criteria were US HCWs aged 18 years or older, including clinical (physician, nurse, and respiratory therapist) and nonclinical (administrative, information technology, and finance) roles. Interventions: Continuing education sessions exposed participants to positive psychology interventions (gratitude letter, work-life integration, self-compassion and cultivating awe). Main outcomes and measures: The primary outcome was emotional exhaustion on day 8; secondary outcomes included emotional thriving, emotional recovery, and work-life integration. All outcomes were measured using psychometrically valid scales previously reported in well-being RCTs and were assessed on days 1 and 8 (primary end point). Differences in outcome measures between the WELL-B intervention group and controls were assessed using t tests. Baseline-adjusted multiple linear regression models were evaluated to examine the association between the WELL-B intervention and the outcome measures after adjusting for additional covariates (sex, race and ethnicity, age, HCW role, and discipline). Intention-to-treat analysis was performed. Results: The cohorts were similar at baseline, mostly female (528 [89%]) and nurses (177 [30%]). A total of 643 respondents participated in the study. In cohort 1, 331 participants initiated WELL-B, and 262 (71%) completed the day 8 follow-up; in cohort 2, 312 participants initiated WELL-B and 291 (77%) completed the day 8 follow-up. Compared with the control cohort, WELL-B significantly improved emotional exhaustion (estimate: -9.0; 95% CI, -13.1 to -4.9; P < .001), emotional thriving (estimate: 6.6; 95% CI, 3.2-10.0; P < .001), emotional recovery (estimate: 5.5; 95% CI, 2.0-9.0; P = .002), and work-life integration (estimate: -5.0; 95% CI, -8.2 to -1.9; P = .002). After adjusting for baseline outcome measures, sex, race and ethnicity, age, HCW role, and discipline, the linear regression model showed WELL-B improved day 8 emotional exhaustion (estimate: -9.6; 95% CI, -12.5 to -6.6; P < .001) compared with the control group. Favorable impressions of WELL-B were reported by more than 90% of the participants. Conclusions and relevance: In this RCT, brief well-being activities delivered during continuing education sessions improved short-term HCW emotional exhaustion, emotional thriving, emotional recovery, and work-life integration, with and without adjusting for covariates. Health care worker impressions of WELL-B were positive. These findings suggest that WELL-B is a beneficial intervention. Trial registration: ClinicalTrials.gov Identifier: NCT05636072.

JAMA network open · randomised controlled trial · 7 citationsread the source →

Adjuvant chemotherapy with cisplatin and gemcitabine versus chemotherapy at relapse in patients with muscle-invasive bladder cancer submitted to radical cystectomy: an Italian, multicenter, randomized phase III trial.

Background: The purpose of the study was to evaluate the benefit of adjuvant chemotherapy (AC) versus surgery alone in patients with muscle-invasive bladder cancer (MIBC). Patients and methods: One hundred and ninety-four patients with pT2G3, pT3-4, N0-2 transitional cell bladder carcinoma were randomly allocated to control (92 patients) or to four courses of AC (102 patients). These latter patients were further randomly assigned to receive gemcitabine 1000 mg/m(2) days 1, 8 and 15 and cisplatin 70 mg/m(2) day 2 or gemcitabine as above plus cisplatin 70 mg/m(2) day 15, every 28 days. Results: At a median follow-up of 35 months, the 5-year overall survival (OS) was 48.5%, with no difference between the two arms [P = 0.24, hazard ratio (HR) 1.29, 95% confidence interval (CI) 0.84-1.99]. Mortality hazard was significantly correlated with Nodes (N) and Tumor (T) stage. The control and AC arms had comparable disease-free survival (42.3% and 37.2%, respectively; P = 0.70, HR 1.08, 95% CI 0.73-1.59). Only 62% of patients received the planned cycles. A significant higher incidence of thrombocytopenia was observed in patients receiving cisplatin on day 2 (P = 0.006). A similar global quality of life was observed in the two arms. Conclusion: The study was underpowered to demonstrate that AC with cisplatin and gemcitabine improves OS and disease-free survival in patients with MIBC.

Annals of oncology : official journal of the European Society for Medical Oncology · randomised controlled trial · 155 citationsread the source →

Inactivated poliovirus vaccine given alone or in a sequential schedule with bivalent oral poliovirus vaccine in Chilean infants: a randomised, controlled, open-label, phase 4, non-inferiority study.

Background: Bivalent oral poliovirus vaccine (bOPV; types 1 and 3) is expected to replace trivalent OPV (tOPV) globally by April, 2016, preceded by the introduction of at least one dose of inactivated poliovirus vaccine (IPV) in routine immunisation programmes to eliminate vaccine-associated or vaccine-derived poliomyelitis from serotype 2 poliovirus. Because data are needed on sequential IPV-bOPV schedules, we assessed the immunogenicity of two different IPV-bOPV schedules compared with an all-IPV schedule in infants. Methods: We did a randomised, controlled, open-label, non-inferiority trial with healthy, full-term (>2·5 kg birthweight) infants aged 8 weeks (± 7 days) at six well-child clinics in Santiago, Chile. We used supplied lists to randomly assign infants (1:1:1) to receive three polio vaccinations (IPV by injection or bOPV as oral drops) at age 8, 16, and 24 weeks in one of three sequential schedules: IPV-bOPV-bOPV, IPV-IPV-bOPV, or IPV-IPV-IPV. We did the randomisation with blocks of 12 stratified by study site. All analyses were done in a masked manner. Co-primary outcomes were non-inferiority of the bOPV-containing schedules compared with the all-IPV schedule for seroconversion (within a 10% margin) and antibody titres (within two-thirds log2 titres) to poliovirus serotypes 1 and 3 at age 28 weeks, analysed in the per-protocol population. Secondary outcomes were seroconversion and titres to serotype 2 and faecal shedding for 4 weeks after a monovalent OPV type 2 challenge at age 28 weeks. Safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01841671, and is closed to new participants. Findings: Between April 25 and August 1, 2013, we assigned 570 infants to treatment: 190 to IPV-bOPV-bOPV, 192 to IPV-IPV-bOPV, and 188 to IPV-IPV-IPV. 564 (99%) were vaccinated and included in the intention-to-treat cohort, and 537 (94%) in the per-protocol analyses. In the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups, respectively, the proportions of children with seroconversion to type 1 poliovirus were 166 (98·8%) of 168, 95% CI 95·8-99·7; 178 (100%), 97·9-100·0; and 175 (100%), 97·9-100·0. Proportions with seroconvsion to type 3 poliovirus were 163 (98·2%) of 166, 94·8-99·4; 177 (100%), 97·9-100·0, and 172 (98·9%) of 174, 95·9-99·7. Non-inferiority was thus shown for the bOPV-containing schedules compared with the all-IPV schedule, with no significant differences between groups. In the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups, respectively, the proportions of children with seroprotective antibody titres to type 1 poliovirus were 168 (98·8%) of 170, 95% CI 95·8-99·7; 181 (100%), 97·9-100·0; and 177 (100%), 97·9-100·0. Proportions to type 3 poliovirus were 166 (98·2%) of 169, 94·9-99·4; 180 (100%), 97·9-100·0; and 174 (98·9%) of 176, 96·0-99·7. Non-inferiority comparisons could not be done for this outcome because median titres for the groups receiving OPV were greater than the assay's upper limit of detection (log2 titres >10·5). The proportions of children seroconverting to type 2 poliovirus in the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups, respectively, were 130 (77·4%) of 168, 95% CI 70·5-83·0; 169 (96·0%) of 176, 92·0-98·0; and 175 (100%), 97·8-100. IPV-bOPV schedules resulted in almost a 0·3 log reduction of type 2 faecal shedding compared with the IPV-only schedule. No participants died during the trial; 81 serious adverse events were reported, of which one was thought to be possibly vaccine-related (intestinal intussusception). Interpretation: Seroconversion rates against polioviruses types 1 and 3 were non-inferior in sequential schedules containing IPV and bOPV, compared with an all-IPV schedule, and proportions of infants with protective antibodies were high after all three schedules. One or two doses of bOPV after IPV boosted intestinal immunity for poliovirus type 2, suggesting possible cross protection. Additionally, there was evidence of humoral priming for type 2 from one dose of IPV. Our findings could give policy makers flexibility when choosing a vaccination schedule, especially when trying to eliminate vaccine-associated and vaccine-derived poliomyelitis. Funding: Bill & Melinda Gates Foundation.

The Lancet. Infectious diseases · randomised controlled trial · 60 citationsread the source →

Low-level laser irradiation improves functional recovery and nerve regeneration in sciatic nerve crush rat injury model.

The development of noninvasive approaches to facilitate the regeneration of post-traumatic nerve injury is important for clinical rehabilitation. In this study, we investigated the effective dose of noninvasive 808-nm low-level laser therapy (LLLT) on sciatic nerve crush rat injury model. Thirty-six male Sprague Dawley rats were divided into 6 experimental groups: a normal group with or without 808-nm LLLT at 8 J/cm(2) and a sciatic nerve crush injury group with or without 808-nm LLLT at 3, 8 or 15 J/cm(2). Rats were given consecutive transcutaneous LLLT at the crush site and sacrificed 20 days after the crush injury. Functional assessments of nerve regeneration were analyzed using the sciatic functional index (SFI) and hindlimb range of motion (ROM). Nerve regeneration was investigated by measuring the myelin sheath thickness of the sciatic nerve using transmission electron microscopy (TEM) and by analyzing the expression of growth-associated protein 43 (GAP43) in sciatic nerve using western blot and immunofluorescence staining. We found that sciatic-injured rats that were irradiated with LLLT at both 3 and 8 J/cm(2) had significantly improved SFI but that a significant improvement of ROM was only found in rats with LLLT at 8 J/cm(2). Furthermore, the myelin sheath thickness and GAP43 expression levels were significantly enhanced in sciatic nerve-crushed rats receiving 808-nm LLLT at 3 and 8 J/cm(2). Taken together, these results suggest that 808-nm LLLT at a low energy density (3 J/cm(2) and 8 J/cm(2)) is capable of enhancing sciatic nerve regeneration following a crush injury.

PloS one · 54 citationsread the source →

Monofocal bone transport technique for bone defects greater than 5 cm in tibia: our experience in a case series of 24 patients.

Background: As the tibial bone defect increases in size, the problems in treatment also increase. The treatment may be problematic but different treatment approaches can be used. Among these approaches, distraction osteogenesis is a method an orthopedic surgeon with limited conditions can use although it has a longer treatment period. In our case series, we evaluated current treatment approaches. Method: Retrospective study based on patient records and radiographs. We evaluated our cases with tibial bone defects Type B and greater than 5 cm. Twenty four cases were operated between 1995 and 2013. Clinical follow-up consisted of physical examination, review of radiographs, and Association for the Study of the Method of Ilizarov (ASAMI) scoring system of bone and functional results. Results: The defects had an average lenght of 7.01 cm (SD:2.88) (range, 5-18). The mean follow-up time from removal of the apparatus to the time of the last clinic visit averaged 74.08 ±24.17 months (range: 39-122). The Ilizarov frame was placed for transport and until bone was solid, average of 275.5 ± 70.6 days (range: 190-437 days). The mean external fixator time (EFT) was 350.91 ± 89.22 days (range: 261-627 days). The mean external fixator index (EFI) was 52 days/cm (range: 34.8-62.8 days/cm). Bone union was obtained in 23/24 (95.8%) patients. Seven patients suffered from stiffness (2 knee, 5 ankle) from which 3 patients developed equinus deformity and required tenoplasty (Achilles tendon lengthening at the time of frame removal. After reaching docking site, 5 patients needed intramedullary nailing to speed up union. Twelve (50%) cases had excellent radiological results, 8 (33%) cases had good, 2 (8%) cases fair and 2 (8%) cases had poor results. Regarding the functional ASAMI scoring system 14 (58%) cases had excellent, 9 (38%) cases had good and one case (4%) had fair result. Conclusion: According to our experience, the Ilizarov bone transport technique remains a reliable method to repair bone defects. However, the treatment time is lengthy with a considerable risk of complications. We found closed intramedullary nailing as an effective and easy solution for cases without pin tract infections to manage the nonunion problem of the docking site and this option should be considered where the surgeon envisages difficulties of healing or the patient has lost patience with the frame. Careful selection of case and patient profile can optimize the outcomes.

Injury · 42 citationsread the source →

Effectiveness of internet-based cognitive behavioural treatment for adolescents with chronic fatigue syndrome (FITNET): a randomised controlled trial.

Background: Chronic fatigue syndrome is characterised by persistent fatigue and severe disability. Cognitive behavioural therapy seems to be a promising treatment, but its availability is restricted. We developed Fatigue In Teenagers on the interNET (FITNET), the first dedicated internet-based therapeutic program for adolescents with this disorder, and compared its effectiveness with that of usual care. Methods: Adolescents aged 12-18 years with chronic fatigue syndrome were assigned to FITNET or usual care in a 1:1 ratio at one tertiary treatment centre in the Netherlands by use of a computer-generated blocked randomisation allocation schedule. The study was open label. Primary outcomes were school attendance, fatigue severity, and physical functioning, and were assessed at 6 months with computerised questionnaires. Analysis was by intention to treat. Thereafter, all patients were offered FITNET if needed. This trial is registered, number ISRCTN59878666. Findings: 68 of 135 adolescents were assigned to FITNET and 67 to usual care, and 67 and 64, respectively, were analysed. FITNET was significantly more effective than was usual care for all dichotomised primary outcomes at 6 months-full school attendance (50 [75%] vs 10 [16%], relative risk 4·8, 95% CI 2·7-8·9; p<0·0001), absence of severe fatigue (57 [85%] vs 17 [27%], 3·2, 2·1-4·9; p<0·0001), and normal physical functioning (52 [78%] vs 13 [20%], 3·8, 2·3-6·3; p<0·0001). No serious adverse events were reported. Interpretation: FITNET offers a readily accessible and highly effective treatment for adolescents with chronic fatigue syndrome. The results of this study justify implementation on a broader scale. Funding: Netherlands Organisation for Health Research and Development.

Lancet (London, England) · randomised controlled trial · 140 citationsread the source →

Sustained-release bupropion versus naltrexone in the treatment of pathological gambling: a preliminary blind-rater study.

Background: Pathological gambling (PG) is a relatively common and highly disabling impulse control disorder. A range of psychotherapeutic agents, including selective serotonin reuptake inhibitors, mood stabilizers, and opioid antagonists, has been shown to be effective in the treatment of PG. The use of selective serotonin reuptake inhibitors and opioid antagonists for PG is consistent with the observation that PG shares features of both the obsessive-compulsive spectrum disorders and addictive disorders. The aim of the study is to compare the effectiveness of sustained-release bupropion versus naltrexone in the treatment of PG. Methods: Thirty-six male pathological gamblers were enrolled in our study. A comprehensive psychiatric diagnostic evaluation was performed at baseline on all patients, and patients were screened for symptoms of gambling, depression, and anxiety using the South Oaks Gambling Screen, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Clinical Global Impression-Severity Scale. In addition, the patients completed self-report questionnaires about their demographic status. Patients were randomized in 2 groups and received either naltrexone (n = 19) or sustained-release bupropion (n = 17) for 12 weeks in a parallel fashion. Treatment response was monitored using the Clinical Global Impression-Improvement Scale which was performed at weeks 2, 4, 8, and 12. Patients were also assessed for the presence of gambling behavior via an unstructured interview, which was also performed at weeks 2, 4, 6, 8, and 12. Raters were blind to the study treatment. Results: The majority of patients responded well to the drug treatment. Twelve of 17 patients in the sustained-release bupropion group completed the 12-week study, and 13 of 19 naltrexone patients completed the study. Nine (75%) of the 12 completers were rated as full responders in the sustained-release bupropion group versus 10 (76%) of 12 in the naltrexone group. Three (25%) of 12 completers in the bupropion group were rated as partial responders. In the naltrexone group, 3 (23%) of 13 completers were rated as partial responders. Full response was defined as the absence of gambling for a 2-week duration together with improvement on the Clinical Global Impression-Improvement Scale. Partial response was defined as a decrease in the frequency of gambling behavior and a decrease in the amount of money spent on gambling. Conclusion: This preliminary study shows that sustained-release bupropion may be effective as naltrexone in the treatment of PG. Further studies are needed to confirm our findings.

Journal of clinical psychopharmacology · randomised controlled trial · 51 citationsread the source →

Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial.

Background: Treatment-resistant major depressive disorder is common; repetitive transcranial magnetic stimulation (rTMS) by use of high-frequency (10 Hz) left-side dorsolateral prefrontal cortex stimulation is an evidence-based treatment for this disorder. Intermittent theta burst stimulation (iTBS) is a newer form of rTMS that can be delivered in 3 min, versus 37·5 min for a standard 10 Hz treatment session. We aimed to establish the clinical effectiveness, safety, and tolerability of iTBS compared with standard 10 Hz rTMS in adults with treatment-resistant depression. Methods: In this randomised, multicentre, non-inferiority clinical trial, we recruited patients who were referred to specialty neurostimulation centres based at three Canadian university hospitals (Centre for Addiction and Mental Health and Toronto Western Hospital, Toronto, ON, and University of British Columbia Hospital, Vancouver, BC). Participants were aged 18-65 years, were diagnosed with a current treatment-resistant major depressive episode or could not tolerate at least two antidepressants in the current episode, were receiving stable antidepressant medication doses for at least 4 weeks before baseline, and had an HRSD-17 score of at least 18. Participants were randomly allocated (1:1) to treatment groups (10 Hz rTMS or iTBS) by use of a random permuted block method, with stratification by site and number of adequate trials in which the antidepressants were unsuccessful. Treatment was delivered open-label but investigators and outcome assessors were masked to treatment groups. Participants were treated with 10 Hz rTMS or iTBS to the left dorsolateral prefrontal cortex, administered on 5 days a week for 4-6 weeks. The primary outcome measure was change in 17-item Hamilton Rating Scale for Depression (HRSD-17) score, with a non-inferiority margin of 2·25 points. For the primary outcome measure, we did a per-protocol analysis of all participants who were randomly allocated to groups and who attained the primary completion point of 4 weeks. This trial is registered with ClinicalTrials.gov, number NCT01887782. Findings: Between Sept 3, 2013, and Oct 3, 2016, we randomly allocated 205 participants to receive 10 Hz rTMS and 209 participants to receive iTBS. 192 (94%) participants in the 10 Hz rTMS group and 193 (92%) in the iTBS group were assessed for the primary outcome after 4-6 weeks of treatment. HRSD-17 scores improved from 23·5 (SD 4·4) to 13·4 (7·8) in the 10 Hz rTMS group and from 23·6 (4·3) to 13·4 (7·9) in the iTBS group (adjusted difference 0·103 [corrected], lower 95% CI -1·16; p=0·0011), which indicated non-inferiority of iTBS. Self-rated intensity of pain associated with treatment was greater in the iTBS group than in the 10 Hz rTMS group (mean score on verbal analogue scale 3·8 [SD 2·0] vs 3·4 [2·0] out of 10; p=0·011). Dropout rates did not differ between groups (10 Hz rTMS: 13 [6%] of 205 participants; iTBS: 16 [8%] of 209 participants); p=0·6004). The most common treatment-related adverse event was headache in both groups (10 Hz rTMS: 131 [64%] of 204; iTBS: 136 [65%] of 208). Interpretation: In patients with treatment-resistant depression, iTBS was non-inferior to 10 Hz rTMS for the treatment of depression. Both treatments had low numbers of dropouts and similar side-effects, safety, and tolerability profiles. By use of iTBS, the number of patients treated per day with current rTMS devices can be increased several times without compromising clinical effectiveness. Funding: Canadian Institutes of Health Research.

Lancet (London, England) · randomised controlled trial · 938 citationsread the source →

The ENCOURAGE mortality risk score and analysis of long-term outcomes after VA-ECMO for acute myocardial infarction with cardiogenic shock.

Purpose: This study was designed to identify factors associated with in-intensive care unit (ICU) death and develop a practical mortality risk score for venoarterial-extracorporeal membrane oxygenation (VA-ECMO)-treated acute myocardial infarction (AMI) patients. Long-term survivors' health-related quality of life (HRQOL), anxiety, depression, and post-traumatic stress disorder (PTSD) frequencies were also assessed. Methods: Data from 138 ECMO-treated AMI patients admitted to two French ICUs (2008-2013) were analyzed. ICU survivors contacted >6 months post-ICU discharge were assessed for HRQOL, psychological and PTSD status. Results: Sixty-five patients (47%) survived to ICU discharge. On the basis of multivariable logistic regression analyses, the ENCOURAGE score was constructed with seven pre-ECMO parameters: age >60, female sex, body mass index >25 kg/m(2), Glasgow coma score <6, creatinine >150 μmol/L, lactate (<2, 2-8, or >8 mmol/L), and prothrombin activity <50%. Six months after ECMO, probabilities of survival were 80, 58, 25, 20, and 7% for ENCOURAGE score classes 0-12, 13-18, 19-22, 23-27, and ≥28, respectively. The ENCOURAGE score ROC AUC [0.84 (95% CI 0.77-0.91)] was significantly better than those of the SAVE, SAPS II, and SOFA scores. Survivors' HRQOL evaluated after median follow-up of 32 months revealed satisfactory mental health but persistent physical and emotional-related difficulties, with 34% (95% CI 20-49%) anxiety, 20% (95% CI 8-32%) depression, and 5% (95% CI 0-12%) PTSD symptoms reported. Conclusions: The ENCOURAGE score might be a useful tool to predict mortality of severe cardiogenic shock AMI patients who received VA-ECMO. However, it now needs prospective validation on other populations of AMI patients.

Intensive care medicine · cohort or longitudinal · 351 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 →

Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): a randomised, blinded, pivotal, device trial.

Background: Long-term loss of arm function after ischaemic stroke is common and might be improved by vagus nerve stimulation paired with rehabilitation. We aimed to determine whether this strategy is a safe and effective treatment for improving arm function after stroke. Methods: In this pivotal, randomised, triple-blind, sham-controlled trial, done in 19 stroke rehabilitation services in the UK and the USA, participants with moderate-to-severe arm weakness, at least 9 months after ischaemic stroke, were randomly assigned (1:1) to either rehabilitation paired with active vagus nerve stimulation (VNS group) or rehabilitation paired with sham stimulation (control group). Randomisation was done by ResearchPoint Global (Austin, TX, USA) using SAS PROC PLAN (SAS Institute Software, Cary, NC, USA), with stratification by region (USA vs UK), age (≤30 years vs >30 years), and baseline Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score (20-35 vs 36-50). Participants, outcomes assessors, and treating therapists were masked to group assignment. All participants were implanted with a vagus nerve stimulation device. The VNS group received 0·8 mA, 100 μs, 30 Hz stimulation pulses, lasting 0·5 s. The control group received 0 mA pulses. Participants received 6 weeks of in-clinic therapy (three times per week; total of 18 sessions) followed by a home exercise programme. The primary outcome was the change in impairment measured by the FMA-UE score on the first day after completion of in-clinic therapy. FMA-UE response rates were also assessed at 90 days after in-clinic therapy (secondary endpoint). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT03131960. Findings: Between Oct 2, 2017, and Sept 12, 2019, 108 participants were randomly assigned to treatment (53 to the VNS group and 55 to the control group). 106 completed the study (one patient for each group did not complete the study). On the first day after completion of in-clinic therapy, the mean FMA-UE score increased by 5·0 points (SD 4·4) in the VNS group and by 2·4 points (3·8) in the control group (between group difference 2·6, 95% CI 1·0-4·2, p=0·0014). 90 days after in-clinic therapy, a clinically meaningful response on the FMA-UE score was achieved in 23 (47%) of 53 patients in the VNS group versus 13 (24%) of 55 patients in the control group (between group difference 24%, 6-41; p=0·0098). There was one serious adverse event related to surgery (vocal cord paresis) in the control group. Interpretation: Vagus nerve stimulation paired with rehabilitation is a novel potential treatment option for people with long-term moderate-to-severe arm impairment after ischaemic stroke. Funding: MicroTransponder.

Lancet (London, England) · randomised controlled trial · 397 citationsread the source →

Cognitive-motor dissociation and time to functional recovery in patients with acute brain injury in the USA: a prospective observational cohort study.

Background: Recovery trajectories of clinically unresponsive patients with acute brain injury are largely uncertain. Brain activation in the absence of a behavioural response to spoken motor commands can be detected by EEG, also known as cognitive-motor dissociation. We aimed to explore the role of cognitive-motor dissociation in predicting time to recovery in patients with acute brain injury. Methods: In this observational cohort study, we prospectively studied two independent cohorts of clinically unresponsive patients (aged ≥18 years) with acute brain injury. Machine learning was applied to EEG recordings to diagnose cognitive-motor dissociation by detecting brain activation in response to verbal commands. Survival statistics and shift analyses were applied to the data to identify an association between cognitive-motor dissociation and time to and magnitude of recovery. The prediction accuracy of the model that was built using the derivation cohort was assessed using the validation cohort. Functional outcomes of all patients were assessed with the Glasgow Outcome Scale-Extended (GOS-E) at hospital discharge and at 3, 6, and 12 months after injury. Patients who underwent withdrawal of life-sustaining therapies were censored, and death was treated as a competing risk. Findings: Between July 1, 2014, and Sept 30, 2021, we screened 598 patients with acute brain injury and included 193 (32%) patients, of whom 100 were in the derivation cohort and 93 were in the validation cohort. At 12 months, 28 (15%) of 193 unresponsive patients had a GOS-E score of 4 or above. Cognitive-motor dissociation was seen in 27 (14%) patients and was an independent predictor of shorter time to good recovery (hazard ratio 5·6 [95% CI 2·5-12·5]), as was underlying traumatic brain injury or subdural haematoma (4·4 [1·4-14·0]), a Glasgow Coma Scale score on admission of greater than or equal to 8 (2·2 [1·0-4·7]), and younger age (1·0 [1·0-1·1]). Among patients discharged home or to a rehabilitation setting, those diagnosed with cognitive-motor dissociation consistently had higher scores on GOS-E indicating better functional recovery compared with those without cognitive-motor dissociation, which was seen as early as 3 months after the injury (odds ratio 4·5 [95% CI 2·0-33·6]). Interpretation: Recovery trajectories of clinically unresponsive patients diagnosed with cognitive-motor dissociation early after brain injury are distinctly different from those without cognitive-motor dissociation. A diagnosis of cognitive-motor dissociation could inform the counselling of families of clinically unresponsive patients, and it could help clinicians to identify patients who will benefit from rehabilitation. Funding: US National Institutes of Health.

The Lancet. Neurology · cohort or longitudinal · 115 citationsread the source →

Sumatriptan-naproxen for acute treatment of migraine: a randomized trial.

Context: Multiple pathogenic mechanisms may be involved in generating the migraine symptom complex, and multimechanism-targeted therapy may confer advantages over monotherapy. Objective: To evaluate the efficacy and safety of a fixed-dose tablet containing sumatriptan succinate and naproxen sodium relative to efficacy and safety of each monotherapy and placebo for the acute treatment of migraine. Design, setting, and participants: Two replicate, randomized, double-blind, single-attack, parallel-group studies conducted among 1461 (study 1) and 1495 (study 2) patients at 118 US clinical centers who were diagnosed as having migraine and received study treatment for a moderate or severe migraine attack. Interventions: Patients were randomized in a 1:1:1:1 ratio to receive a single tablet containing sumatriptan, 85 mg, and naproxen sodium, 500 mg; sumatriptan, 85 mg (monotherapy); naproxen sodium, 500 mg (monotherapy); or placebo, to be used after onset of a migraine with moderate to severe pain. Main outcome measures: Primary outcome measures included the percentages of patients with headache relief 2 hours after dosing, absence of photophobia, absence of phonophobia, and absence of nausea for the comparison between sumatriptan-naproxen sodium and placebo, and the percentages of patients with sustained pain-free response for the comparison between sumatriptan-naproxen sodium and each monotherapy. Results: Sumatriptan-naproxen sodium was more effective than placebo for headache relief at 2 hours after dosing (study 1, 65% vs 28%; P<.001 and study 2, 57% vs 29%; P<.001), absence of photophobia at 2 hours (58% vs 26%; P<.001 and 50% vs 32%; P<.001), and absence of phonophobia at 2 hours (61% vs 38%; P<.001 and 56% vs 34%; P<.001). The absence of nausea 2 hours after dosing was higher with sumatriptan-naproxen sodium than placebo in study 1 (71% vs 65%; P = .007), but in study 2 rates of absence of nausea did not differ between sumatriptan-naproxen sodium and placebo (65% vs 64%; P = .71). For 2- to 24-hour sustained pain-free response, sumatriptan-naproxen sodium was superior at P<.01 (25% and 23% in studies 1 and 2, respectively) to sumatriptan monotherapy (16% and 14% in studies 1 and 2), naproxen sodium monotherapy (10% and 10% in studies 1 and 2), and placebo (8% and 7% in studies 1 and 2). The incidence of adverse events was similar between sumatriptan-naproxen sodium and sumatriptan monotherapy. Conclusion: Sumatriptan, 85 mg, plus naproxen sodium, 500 mg, as a single tablet for acute treatment of migraine resulted in more favorable clinical benefits compared with either monotherapy, with an acceptable and well-tolerated adverse effect profile. Trial registration: clinicaltrials.gov Identifiers: NCT00434083 (study 1); NCT00433732 (study 2).

JAMA · randomised controlled trial · 181 citationsread the source →

Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010.

Background: We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to estimate the burden of disease attributable to mental and substance use disorders in terms of disability-adjusted life years (DALYs), years of life lost to premature mortality (YLLs), and years lived with disability (YLDs). Methods: For each of the 20 mental and substance use disorders included in GBD 2010, we systematically reviewed epidemiological data and used a Bayesian meta-regression tool, DisMod-MR, to model prevalence by age, sex, country, region, and year. We obtained disability weights from representative community surveys and an internet-based survey to calculate YLDs. We calculated premature mortality as YLLs from cause of death estimates for 1980-2010 for 20 age groups, both sexes, and 187 countries. We derived DALYs from the sum of YLDs and YLLs. We adjusted burden estimates for comorbidity and present them with 95% uncertainty intervals. Findings: In 2010, mental and substance use disorders accounted for 183·9 million DALYs (95% UI 153·5 million-216·7 million), or 7·4% (6·2-8·6) of all DALYs worldwide. Such disorders accounted for 8·6 million YLLs (6·5 million-12·1 million; 0·5% [0·4-0·7] of all YLLs) and 175·3 million YLDs (144·5 million-207·8 million; 22·9% [18·6-27·2] of all YLDs). Mental and substance use disorders were the leading cause of YLDs worldwide. Depressive disorders accounted for 40·5% (31·7-49·2) of DALYs caused by mental and substance use disorders, with anxiety disorders accounting for 14·6% (11·2-18·4), illicit drug use disorders for 10·9% (8·9-13·2), alcohol use disorders for 9·6% (7·7-11·8), schizophrenia for 7·4% (5·0-9·8), bipolar disorder for 7·0% (4·4-10·3), pervasive developmental disorders for 4·2% (3·2-5·3), childhood behavioural disorders for 3·4% (2·2-4·7), and eating disorders for 1·2% (0·9-1·5). DALYs varied by age and sex, with the highest proportion of total DALYs occurring in people aged 10-29 years. The burden of mental and substance use disorders increased by 37·6% between 1990 and 2010, which for most disorders was driven by population growth and ageing. Interpretation: Despite the apparently small contribution of YLLs--with deaths in people with mental disorders coded to the physical cause of death and suicide coded to the category of injuries under self-harm--our findings show the striking and growing challenge that these disorders pose for health systems in developed and developing regions. In view of the magnitude of their contribution, improvement in population health is only possible if countries make the prevention and treatment of mental and substance use disorders a public health priority. Funding: Queensland Department of Health, National Health and Medical Research Council of Australia, National Drug and Alcohol Research Centre-University of New South Wales, Bill & Melinda Gates Foundation, University of Toronto, Technische Universität, Ontario Ministry of Health and Long Term Care, and the US National Institute of Alcohol Abuse and Alcoholism.

Lancet (London, England) · review · 3758 citationsread the source →

Sleep deprivation selectively enhances interpersonal emotion recognition from dynamic facial expressions at long viewing times: An observational study.

Observational and experimental studies have shown that sleep deprivation disinhibits emotional responses to disturbing and rewarding external events. On the other hand, most studies on sleep deprivation and interpersonal emotion recognition report that sensitivity to others' emotions is dampened during sleep deprivation. This is at odds with current neuroscientific theories of social cognition that assume that affective experiences and emotion recognition in others are closely tied at the neural and physiological level. In this observational study we show that sleep deprivation can actually increase emotion recognition accuracy from dynamically unfolding facial expressions if they are viewed sufficiently long. Participants viewed 2-4 s or 8-10s video clips of female senders who facially communicated anger, disgust, fear or sadness to their romantic partner and evaluated the sender's affective state in a forced-choice paradigm, either during sleep deprivation after a night shift (N = 40) or after normal night sleep (N = 50). All participants showed a significant increase in emotion recognition accuracy from 2-4 s to 8-10 s stimulus presentation times. Emotion recognition accuracy did not differ between sleep-deprived and control participants for 2-4 s videos, but sleep-deprived participants showed significantly higher emotion recognition accuracy than control participants for 8-10 s videos. We surmise that this effect might be due to the break-down of prefrontal activity associated with sleep deprivation, which might not only disinhibit affective responses to external events but might also release simulation-based neural processes that contribute to interpersonal emotion recognition from dynamic facial expressions at longer time scales than usually investigated in emotion recognition studies.

Neuroscience letters · cohort or longitudinal · 5 citationsread the source →

The effects of psychological intervention on atopic dermatitis. A systematic review and meta-analysis.

Background: Psychological interventions may be valuable in atopic dermatitis. We systematically reviewed and carried out a meta-analysis of randomized controlled trials of psychological interventions. Methods: Electronic searches and manual journal searches were carried out. Two coders independently coded study designs, participants, treatments and outcome characteristics of the studies meeting the selection criteria. Results: Eight journal articles published between 1986 and 2006 were included. Eight types of intervention were tested: aromatherapy, autogenic training, brief dynamic psychotherapy, cognitive-behavioral therapy, dermatological education and cognitive-behavioral therapy, habit reversal behavioral therapy, a stress management program, and structured educational programs. Effect sizes were computed as correlation coefficient (r), and random effects models were used in the analysis. For eczema severity, the average effect size for the 8 trials including 8 interventions was -0.367 [chi(2)(1) = 7.452, p = 0.006; 95% CI -0.579 to -0.108]. The average effect sizes on itching intensity (5 trials with 5 interventions) and scratching (5 trials with 4 interventions) were -0.805 [chi(2)(1) = 4.719, p = 0.030; 95% CI -0.971 to -0.108] and -0.620 [chi(2)(1) = 24.24, p < 0.0001; 95% CI -0.767 to -0.410], respectively. Conclusions: Although the present meta-analysis revealed that psychological interventions had a significant ameliorating effect on eczema severity, itching intensity and scratching in atopic dermatitis patients, a definite conclusion about their effectiveness seems premature. Accordingly, future studies should involve more sophisticated methodologies, use established measures of outcome variables, adjust for possible confounders between the intervention and control groups, and provide sufficient data to calculate the effect sizes for future meta-analyses.

International archives of allergy and immunology · meta-analysis · 82 citationsread the source →

Hand Posturing Is a Nonverbal Indicator of Catastrophic Thinking for Finger, Hand, or Wrist Injury.

Background: Prior research documents that greater psychologic distress (anxiety/depression) and less effective coping strategies (catastrophic thinking, kinesophobia) are associated with greater pain intensity and greater limitations. Recognition and acknowledgment of verbal and nonverbal indicators of psychologic factors might raise opportunities for improved psychologic health. There is evidence that specific patient words and phrases indicate greater catastrophic thinking. This study tested proposed nonverbal indicators (such as flexion of the wrist during attempted finger flexion or extension of uninjured fingers as the stiff and painful finger is flexed) for their association with catastrophic thinking. Questions/purposes: (1) Do patients with specific protective hand postures during physical examination have greater pain interference (limitation of activity in response to nociception), limitations, symptoms of depression, catastrophic thinking (protectiveness, preparation for the worst), and kinesophobia (fear of movement)? (2) Do greater numbers of protective hand postures correlate with worse scores on these measures? Methods: Between October 2014 and September 2016, 156 adult patients with stiff or painful fingers within 2 months after sustaining a finger, hand, or wrist injury were invited to participate in this study. Six patients chose not to participate as a result of time constraints and one patient was excluded as a result of inconsistent scoring of a possible hand posture, leaving 149 patients for analysis. We asked all patients to complete a set of questionnaires and a sociodemographic survey. We used Patient Reported Outcomes Measurement Information System (PROMIS) Depression, Upper Extremity Physical Function, and Pain Interference computer adaptive test (CAT) questionnaires. We used the Abbreviated Pain Catastrophizing Scale (PCS-4) to measure catastrophic thinking in response to nociception. Finally, we used the Tampa Scale of Kinesophobia (TSK) to assess fear of movement. The occurrence of protective hand postures during the physical examination was noted by both the physician and researcher. For uncertainty or disagreement, a video of the physical examination was recorded and a group decision was made. Results: Patients with one or more protective hand postures did not score higher on the PROMIS Pain Interference CAT (hand posture: 59 [56-64]; no posture: 59 [54-63]; difference of medians: 0; p = 0.273), Physical Function CAT (32 ± 8 versus 34 ± 8; mean difference: 2 [confidence interval {CI}, -0.5 to 5]; p = 0.107), nor the Depression CAT (48 [41-55] versus 48 [42-53]; difference of medians: 0; p = 0.662). However, having at least one hand posture was associated with a higher degree of catastrophic thinking (PCS scores: 13 [6-26] versus 10 [3-16]; difference of medians: 3; p = 0.0104) and a higher level of kinesophobia (TSK: 40 ± 6 versus 38 ± 6; mean difference: -2 [CI, -4 to -1]; p = 0.0420). Greater catastrophic thinking was associated with a greater number of protective hand postures on average (rho: 0.20, p = 0.0138). Conclusions: Protective hand postures and (based on prior research) specific words and phrases are associated with catastrophic thinking and kinesophobia, less effective coping strategies that hinder recovery. Surgeons can learn to recognize these signs and begin to treat catastrophic thinking and kinesophobia starting with compassion, empathy, and patience and be prepared to add formal support (such as cognitive-behavioral therapy) to help facilitate recovery. Level of evidence: Level III, diagnostic study.

Clinical orthopaedics and related research · cohort or longitudinal · 35 citationsread the source →

Diet quality indices and their associations with health-related outcomes in children and adolescents: an updated systematic review.

Background: To describe a-priori diet quality indices used in children and adolescents, appraise the validity and reliability of these indices, and synthesise evidence on the relationship between diet quality and physical and mental health, and growth-related outcomes. Methods: Five electronic databases were searched until January 2019. An a-priori diet quality index was included if it applied a scoring structure to rate child or adolescent (aged 0-18-years) dietary intakes relative to dietary or nutrient guidelines. Diagnostic accuracy studies and prospective cohort studies reporting health outcomes were appraised using the Academy of Nutrition and Dietetics Quality Criteria Checklist. Results: From 15,577 records screened, 128 unique paediatric diet quality indices were identified from 33 countries. Half of the indices' scores rated both food and nutrient intakes (n = 65 indices). Some indices were age specific: infant (< 24-months; n = 8 indices), child (2-12-years; n = 16), adolescent (13-18 years; n = 8), and child/adolescent (n = 14). Thirty-seven indices evaluated for validity and/or reliability. Eleven of the 15 indices which investigated associations with prospective health outcomes reported significant results, such as improved IQ, quality of life, blood pressure, body composition, and prevalence of metabolic syndrome. Conclusions: Research utilising diet quality indices in paediatric populations is rapidly expanding internationally. However, few indices have been evaluated for validity, reliability, or association with health outcomes. Further research is needed to determine the validity, reliability, and association with health of frequently utilised diet quality indices to ensure data generated by an index is useful, applicable, and relevant. Registration: PROSPERO number: CRD42018107630 .

Nutrition journal · systematic review · 103 citationsread the source →

Attention Bias Modification training in individuals with depressive symptoms: A randomized controlled trial.

Background and objectives: Negative attentional biases are often considered to have a causal role in the onset and maintenance of depressive symptoms. This suggests that reduction of such biases may be a plausible strategy in the treatment of depressive symptoms. The present clinical randomized controlled trial examined long-term effects of a computerized attention bias modification (ABM) procedure on individuals with elevated depressive symptoms. Methods: In a double-blind study design, 77 individuals with ongoing mild to severe symptoms of depression were randomly assigned to one of three conditions: 1) ABM training (n = 27); 2) placebo (n = 27); 3) assessment-only (n = 23). In both the ABM and placebo conditions, participants completed 8 sessions of 216-trials (1728 in total) during a 2-week period. Assessments were conducted at pre-training and post-training (0, 2, 4, 8-week, 3, 7-month follow-ups). Change in depressive symptoms and restoration of asymptomatic level were the primary outcome measures. Results: In the ABM, but not the other two conditions, significant reductions in depressive symptoms were found at post-training and maintained during the 3-month follow-up. Importantly, more participants remained asymptomatic in the ABM condition, as compared to the other two conditions, from post-training to 7-month follow-up. ABM also significantly reduced secondary outcome measures including rumination and trait anxiety, and notably, the ABM effect on reducing depressive symptoms was mediated by rumination. Limitation: Generalization of the findings may be limited because the present sample included only college students. Conclusions: The ABM effect on reducing depressive symptoms was maintained for at least 3-month duration in individuals with elevated depressive symptoms, and these results suggest that ABM may be a useful tool for the prevention of depressive symptoms. CLINICALTRIALS.GOV: NCT01628016.

Journal of behavior therapy and experimental psychiatry · randomised controlled trial · 91 citationsread the source →

Prevalence of symptoms of anxiety and depression in patients with inflammatory bowel disease: a systematic review and meta-analysis.

Background: Inflammatory bowel disease (IBD) is a lifelong condition with no cure. Patients with IBD might experience symptoms of common mental disorders such as anxiety and depression because of bidirectional communication via the gut-brain axis and chronicity of symptoms, and because of impaired quality of life and reduced social functioning. However, uncertainties remain about the magnitude of this problem. We aimed to assess prevalence of symptoms of anxiety or depression in adult patients with IBD. Methods: In this systematic review and meta-analysis, we searched MEDLINE, Embase, Embase Classic, and PsycINFO for papers published from inception to Sept 30, 2020, reporting observational studies that recruited at least 100 adult patients with IBD and that reported prevalence of symptoms of anxiety or depression according to validated screening instruments. We excluded studies that only used a structured interview to assess for these symptoms and studies that did not provide extractable data. We extracted data from published study reports and calculated pooled prevalences of symptoms of anxiety and depression, odds ratios (OR), and 95% CIs. Findings: Of 5544 studies identified, 77 fulfilled the eligibility criteria, including 30 118 patients in total. Overall, pooled prevalence of anxiety symptoms was 32·1% (95% CI 28·3-36·0) in 58 studies (I2=96·9%) and pooled prevalence of depression symptoms was 25·2% (22·0-28·5) in 75 studies (I2=97·6%). In studies that reported prevalence of anxiety or depression in patients with Crohn's disease and ulcerative colitis within the same study population, patients with Crohn's disease had higher odds of anxiety symptoms (OR 1·2, 95% CI 1·1-1·4) and depression symptoms (1·2, 1·1-1·4) than patients with ulcerative colitis. Overall, women with IBD were more likely to have symptoms of anxiety than were men with IBD (pooled prevalence 33·8% [95% CI 26·5-41·5] for women vs 22·8% [18·7-27·2] for men; OR 1·7 [95% CI 1·2-2·3]). They were also more likely to have symptoms of depression than men were (pooled prevalence 21·2% [95% CI 15·4-27·6] for women vs 16·2% [12·6-20·3] for men; OR 1·3 [95% CI 1·0-1·8]). The prevalence of symptoms of anxiety (57·6% [95% CI 38·6-75·4]) or depression (38·9% [26·2-52·3]) was higher in patients with active IBD than in patients with inactive disease (38·1% [30·9-45·7] for anxiety symptoms and 24·2% [14·7-35·3] for depression symptoms; ORs 2·5 [95% CI 1·5-4·1] for anxiety and 3·1 [1·9-4·9] for depression). Interpretation: There is a high prevalence of symptoms of anxiety and depression in patients with IBD, with up to a third of patients affected by anxiety symptoms and a quarter affected by depression symptoms. Prevalence was also increased in patients with active disease: half of these patients met criteria for anxiety symptoms and a third met criteria for depression symptoms. Encouraging gastroenterologists to screen for and treat these disorders might improve outcomes for patients with IBD. Funding: None.

The lancet. Gastroenterology & hepatology · meta-analysis · 514 citationsread the source →

Impact of a mental health teaching programme on adolescents.

Background: Child and adolescent mental health disorders are present in around 10% of the population. Research indicates that many young people possess negative attitudes towards mental health difficulties among peers. Aims: To assess the impact of a mental health teaching programme on adolescent pupils' understanding. Method: Two-group pre-test-post-test control group study in two English secondary schools. Experimental classes (School E) received a six-lesson teaching intervention on mental health; control classes (School C) did not. Participants were 14- and 15-year-old pupils. The intervention consisted of six lessons on mental health issues common to young people: stress; depression; suicide/self-harm; eating disorders; being bullied; and intellectual disability. School C was given access to these lesson plans and materials on completion of the study. Understanding was measured at two time points, Time 1 (T(1)) and Time 2 (T(2)), 8 months apart, by a Mental Health Questionnaire. Behavioural, emotional and relationship strengths and difficulties were measured by the self-rated Strengths and Difficulties Questionnaire (SDQ) with five subscales: hyperactivity, emotional symptoms, conduct problems, peer problems and prosocial behaviour. Results: At T(2), pupils in School E compared with those in School C showed significantly more sensitivity and empathy towards people with mental health difficulties. They also used significantly fewer pejorative expressions to describe mental health difficulties. There was a significant reduction in SDQ scores on conduct problems and a significant increase on prosocial behaviour among School E pupils compared with controls. Pupils valued the intervention highly, in particular the lessons on suicide/self-harm. Conclusions: Teaching 14- and 15-year-olds about mental health difficulties helps to reduce stigma by increasing knowledge and promoting positive attitudes. The intervention also reduced self-reported conduct problems and increased prosocial behaviour. Generally, participating pupils were positive about the importance of lessons on mental health, and said that they had learnt much about the lesson topics.

The British journal of psychiatry : the journal of mental science · cohort or longitudinal · 42 citationsread the source →

Loneliness before and during the COVID-19 pandemic: A systematic review with meta-analysis.

The COVID-19 pandemic and measures aimed at its mitigation, such as physical distancing, have been discussed as risk factors for loneliness, which increases the risk of premature mortality and mental and physical health conditions. To ascertain whether loneliness has increased since the start of the pandemic, this study aimed to narratively and statistically synthesize relevant high-quality primary studies. This systematic review with meta-analysis was registered at PROSPERO (ID CRD42021246771). Searched databases were PubMed, PsycINFO, Cochrane Library/Central Register of Controlled Trials/EMBASE/CINAHL, Web of Science, the World Health Organization (WHO) COVID-19 database, supplemented by Google Scholar and citation searching (cutoff date of the systematic search December 5, 2021). Summary data from prospective research including loneliness assessments before and during the pandemic were extracted. Of 6,850 retrieved records, 34 studies (23 longitudinal, 9 pseudolongitudinal, 2 reporting both designs) on 215,026 participants were included. Risk of bias (RoB) was estimated using the risk of bias in non-randomised studies-of interventions (ROBINS-I) tool. Standardized mean differences (SMD, Hedges' g) for continuous loneliness values and logOR for loneliness prevalence rates were calculated as pooled effect size estimators in random-effects meta-analyses. Pooling studies with longitudinal designs only (overall N = 45,734), loneliness scores (19 studies, SMD = 0.27 [95% confidence interval = 0.14-0.40], Z = 4.02, p < .001, I 2 = 98%) and prevalence rates (8 studies, logOR = 0.33 [0.04-0.62], Z = 2.25, p = .02, I 2 = 96%) increased relative to prepandemic times with small effect sizes. Results were robust with respect to studies' overall RoB, pseudolongitudinal designs, timing of prepandemic assessments, and clinical populations. The heterogeneity of effects indicates a need to further investigate risk and protective factors as the pandemic progresses to inform targeted interventions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The American psychologist · meta-analysis · 317 citationsread the source →

Neuropsychiatric phenotypes in children with Noonan syndrome.

Aim: We investigated neuropsychiatric outcomes in children with Noonan syndrome and addressed limitations in previous research with a focus on prepubertal children, comparison to typically developing children, comprehensive neuropsychiatric evaluation, and controlling for overall cognitive abilities. Method: Forty-five children with Noonan syndrome (mean = 8 years 6 months, SD = 2 years 2 months; 29 females) and 40 typically developing children (mean = 8 years 9 months, SD = 2 years; 22 females) were evaluated with objective, parent-report, and psychiatric interview measures. Results: Children with Noonan syndrome demonstrated elevated symptoms across attention-deficit/hyperactivity disorder (ADHD) (attention, hyperactivity, and inhibition), autism spectrum disorder (ASD) (maintaining social relationships, behavioral rigidity, and sensory sensitivity), and oppositional defiant disorder (ODD) (aggression) symptom clusters relative to typically developing children (all p < 0.05). Group differences in nearly all parent-report measures were significant after accounting for variations in intellectual functioning, suggesting that increased neurodevelopmental symptoms are not simply driven by overall intelligence. Twenty out of 42 children with Noonan syndrome met criteria for ADHD, eight out of 42 for ODD, and 11 out of 43 demonstrated clinically significant symptoms seen in children with ASD. Interpretation: Children with Noonan syndrome are at increased risk for a range of ADHD, ASD, and ODD associated symptoms. A dimensional approach reveals significant ASD symptoms in Noonan syndrome that do not emerge when using the currently accepted categorical diagnostic approach. What this paper adds: Neuropsychiatric disorders occur in more than half of children with Noonan syndrome. Children with Noonan syndrome demonstrate highly variable neurodevelopmental symptom profiles. Children with Noonan syndrome display variable impairments in attention, hyperactivity, and inhibition. Specific social concerns include behavioral rigidity, transitions, and difficulties maintaining social relationships. Children with Noonan syndrome display variably elevated levels of aggression and emotional dysregulation.

Developmental medicine and child neurology · 34 citationsread the source →

Airway glutathione homeostasis is altered in children with severe asthma: evidence for oxidant stress.

Background: Severe asthma is characterized by persistent airway inflammation and increased formation of reactive oxygen species. Objectives: Glutathione (GSH) is an important antioxidant in the epithelial lining fluid (ELF). We hypothesized that airway GSH homeostasis was altered in children with severe asthma and was characterized by decreased GSH and increased glutathione disulfide (GSSG) concentrations. Methods: Bronchoalveolar lavage was obtained from 65 children with severe asthma, including 35 children with baseline airway obstruction evidenced by FEV(1) <80%. Control data were obtained from 6 children with psychogenic (habit) cough or vocal cord dysfunction undergoing diagnostic bronchoscopy and 35 healthy adult controls. GSH, GSSG, and other determinants of airway oxidative stress including glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), malondialdehyde, 8-isoprostane, and H(2)O(2) were measured in the ELF. The ELF redox potential was calculated from GSH and GSSG by using the Nernst equation. Results: Compared with controls, subjects with severe asthma had lower airway GSH with increased GSSG despite no differences in GST, GR, and GPx activities between groups. This was accompanied by increased malondialdehyde, 8-isoprostane, and H(2)O(2) concentrations in the ELF. GSH oxidation was most apparent in subjects with severe asthma with airway obstruction and was supported by an upward shift in the ELF GSH redox potential. Conclusion: Children with severe asthma have increased biomarkers of oxidant stress in the ELF that are associated with increased formation of GSSG and a shift in the GSH redox potential toward the more oxidized state.

The Journal of allergy and clinical immunology · 138 citationsread the source →

Refinement of a meaning-centered counseling program for Chinese patients with advanced cancer: integrating cultural adaptation and implementation science approaches.

Background: This mixed methods study identified needed refinements to a telehealth-delivered cultural and linguistic adaptation of Meaning-Centered Psychotherapy for Chinese patients with advanced cancer (MCP-Ch) to enhance acceptability, comprehensibility, and implementation of the intervention in usual care settings, guided by the Ecological Validity Model (EVM) and the Practical, Robust Implementation and Sustainability Model (PRISM). Methods: Fifteen purposively sampled mental health professionals who work with Chinese cancer patients completed surveys providing Likert-scale ratings on acceptability and comprehensibility of MCP-Ch content (guided by the EVM) and pre-implementation factors (guided by PRISM), followed by semi-structured interviews. Survey data were descriptively summarized and linked to qualitative interview data. Three analysts independently coded the transcripts according to EVM and PRISM domains; discrepancies were resolved through discussion and consensus. Results: Quantitative findings showed high appropriateness and relevance of MCP-Ch across five EVM domains of Language, Metaphors/Stories, Goals, Content, and Concepts. Qualitative analysis yielded 23 inductive codes under the seven EVM domains: (1) Language (3 subcodes), (2) Persons (2 subcodes), (3) Metaphors/Stories (2 subcodes), (4) Methods (8 subcodes), (5) Content (2 subcodes), (6) Goals (4 subcodes), and (7) Concepts (2 subcodes). Themes based on PRISM included (1) Intervention characteristics (organizational perspective, 7 subcodes; and patient perspective, 6 subcodes) (2) External environment (2 subcodes), (3) Implementation and sustainability infrastructure (4 subcodes), and (4) Recipients (organizational characteristics, 5 subcodes; and patient characteristics, 4 subcodes). Conclusion: Recommendations for next steps include increasing the MCP-Ch protocol's flexibility and adaptability to allow interventionists to flexibly tailor MCP-Ch material to meet patients' individual needs, simplifying content to improve comprehension and acceptability, providing additional training to Chinese-serving providers to increase adoption and sustainability, and considering interpreter-assisted delivery to increase access. Findings yielded important information to maximize cultural relevance as well as the implementation and sustainability potential of MCP-Ch in real-world settings.

BMC health services research · 6 citationsread the source →

Testing the Pragmatic Effectiveness of a Consumer-Based Mindfulness Mobile App in the Workplace: Randomized Controlled Trial.

Background: Mental health and sleep problems are prevalent in the workforce, corresponding to costly impairment in productivity and increased health care use. Digital mindfulness interventions are efficacious in improving sleep and mental health in the workplace; however, evidence supporting their pragmatic utility, potential for improving productivity, and ability to reduce employer costs is limited. Objective: This pragmatic, cluster randomized controlled trial aimed to evaluate the experimental effects of implementing a commercially available mindfulness app-Calm-in employees of a large, multisite employer in the United States. Outcomes included mental health (depression, anxiety, and stress), sleep (insomnia and daytime sleepiness), resilience, productivity impairment (absenteeism, presenteeism, overall work impairment, and non-work activity impairment), and health care use (medical visit frequency). Methods: Employees were randomized at the work site to receive either the Calm app intervention or waitlist control. Participants in the Calm intervention group were instructed to use the Calm app for 10 minutes per day for 8 weeks; individuals with elevated baseline insomnia symptoms could opt-in to 6 weeks of sleep coaching. All outcomes were assessed every 2 weeks, with the exception of medical visits (weeks 4 and 8 only). Effects of the Calm intervention on outcomes were evaluated via mixed effects modeling, controlling for relevant baseline characteristics, with fixed effects of the intervention on outcomes assessed at weeks 2, 4, 6, and 8. Models were analyzed via complete-case and intent-to-treat analyses. Results: A total of 1029 employees enrolled (n=585 in the Calm intervention group, including 101 who opted-in to sleep coaching, and n=444 in waitlist control). Of them, 192 (n=88 for the Calm intervention group and n=104 for waitlist) completed all 5 assessments. In the complete-case analysis at week 8, employees at sites randomized to the Calm intervention group experienced significant improvements in depression (P=.02), anxiety (P=.01), stress (P<.001), insomnia (P<.001), sleepiness (P<.001), resilience (P=.02), presenteeism (P=.01), overall work impairment (P=.004), and nonwork impairment (P<.001), and reduced medical care visit frequency (P<.001) and productivity impairment costs (P=.01), relative to the waitlist control. In the intent-to-treat analysis at week 8, significant benefits of the intervention were observed for depression (P=.046), anxiety (P=.01), insomnia (P<.001), sleepiness (P<.001), nonwork impairment (P=.04), and medical visit frequency (P<.001). Conclusions: The results suggest that the Calm app is an effective workplace intervention for improving mental health, sleep, resilience, and productivity and for reducing medical visits and costs owing to work impairment. Future studies should identify optimal implementation strategies that maximize employee uptake and large-scale implementation success across diverse, geographically dispersed employers. Trial registration: ClinicalTrials.gov NCT05120310; https://clinicaltrials.gov/ct2/show/NCT05120310.

JMIR mHealth and uHealth · randomised controlled trial · 28 citationsread the source →

From grief, guilt pain and stigma to hope and pride - a systematic review and meta-analysis of mixed-method research of the psychosocial impact of stillbirth.

Background: Despite improvements in maternity healthcare services over the last few decades, more than 2.7 million babies worldwide are stillborn each year. The global health agenda is silent about stillbirth, perhaps, in part, because its wider impact has not been systematically analysed or understood before now across the world. Our study aimed to systematically review, evaluate and summarise the current evidence regarding the psychosocial impact of stillbirth to parents and their families, with the aim of improving guidance in bereavement care worldwide. Methods: Systematic review and meta-summary (quantitative aggregation of qualitative findings) of quantitative, qualitative, and mixed-methods studies. All languages and countries were included. Results: Two thousand, six hundred and nineteen abstracts were identified; 144 studies were included. Frequency effect sizes (FES %) were calculated for each theme, as a measure of their prevalence in the literature. Themes ranged from negative psychological symptoms post bereavement (77 · 1) and in subsequent pregnancies (27 · 1), to disenfranchised grief (31 · 2), and incongruent grief (28 · 5), There was also impact on siblings (23 · 6) and on the wider family (2 · 8). They included mixed-feelings about decisions made when the baby died (12 · 5), avoidance of memories (13 · 2), anxiety over other children (7 · 6), chronic pain and fatigue (6 · 9), and a different approach to the use of healthcare services (6 · 9). Some themes were particularly prominent in studies of fathers; grief suppression (avoidance)(18 · 1), employment difficulties, financial debt (5 · 6), and increased substance use (4 · 2). Others found in studies specific to mothers included altered body image (3 · 5) and impact on quality of life (2 · 1). Counter-intuitively, Some themes had mixed connotations. These included parental pride in the baby (5 · 6), motivation for engagement in healthcare improvement (4 · 2) and changed approaches to life and death, self-esteem, and own identity (25 · 7). In studies from low/middle income countries, stigmatisation (13 · 2) and pressure to prioritise or delay conception (9) were especially prevalent. Conclusion: Experiencing the birth of a stillborn child is a life-changing event. The focus of the consequences may vary with parent gender and country. Stillbirth can have devastating psychological, physical and social costs, with ongoing effects on interpersonal relationships and subsequently born children. However, parents who experience the tragedy of stillbirth can develop resilience and new life-skills and capacities. Future research should focus on developing interventions that may reduce the psychosocial cost of stillbirth.

BMC pregnancy and childbirth · meta-analysis · 201 citationsread the source →

Impact of coronavirus syndromes on physical and mental health of health care workers: Systematic review and meta-analysis.

Background: Health care workers (HCW) are at high risk of developing physical/mental health outcomes related to coronavirus syndromes. Nature and frequency of these outcomes are undetermined. Methods: PRISMA/MOOSE-compliant (PROSPERO-CRD42020180205) systematic review of Web of Science/grey literature until 15th April 2020, to identify studies reporting physical/mental health outcomes in HCW infected/exposed to Severe Acute Respiratory Syndrome -SARS-, Middle East Respiratory Syndrome -MERS-, Novel coronavirus -COVID-19-. Proportion random effect meta-analyses, I2 statistic, quality assessment and sensitivity analysis. Results: 115 articles were included (n=60,458 HCW, age 36.1±7.1, 77.1% female). Physical health outcomes: 75.9% HCW infected by SARS/MERS/COVID-19 reported fever (95%CI=65.9-83.7%, k=12, n=949), 47.9% cough (95%CI=39.2-56.8%, k=14, n=970), 43.6% myalgias (95%CI=31.9-56.0%, k=13, n=898), 42.3% chills (95%CI=20.2-67.9%, k=7, n=716), 41.2% fatigue (95%CI=18.2-68.8%, k=6, n=386), 34.6% headaches (95%CI=23.1-48.2%, k=11, n=893), 31.2% dyspnoea (95%CI=23.2-40.5%, k=12, n=1003), 25.3% sore throat (95%CI=18.8-33.2%, k=8, n=747), 22.2% nausea/vomiting (95%CI=14.9-31.8%, k=6, n=662), 18.8% diarrhoea (95%CI=11.9-28.4%, k=9, n=824). Mental health outcomes: 62.5% HCW exposed to SARS/MERS/COVID-19 reported general health concerns (95%CI=57.0-67,8%, k=2, n=2254), 43.7% fear (95%CI=33.9-54.0%, k=4, n=584), 37.9% insomnia (95%CI=30.9-45.5%, k=6, n=5067), 37.8% psychological distress (95%CI=28.4-48.2%, k=15, n=24,346), 34.4% burnout (95%CI=19.3-53.5%, k=3, n=1337), 29.0% anxiety features (95%CI=14.2-50.3%, k=6, n=9191), 26.3% depressive symptoms (95%CI=12.5-47.1%, k=8, n=9893), 20.7% post-traumatic stress disorder features (95%CI=13.2-31%, k=11, n=3826), 16.1% somatisation (95%CI=0.2-96.0%, k=2, n=2184), 14.0% stigmatisation feelings (95%CI=6.4-28.1%, k=2, n=411). Limitations: Limited amount of evidence for some outcomes and suboptimal design in several studies included. Conclusions: SARS/MERS/COVID-19 have a substantial impact on the physical and mental health of HCW, which should become a priority for public health strategies.

Journal of affective disorders · meta-analysis · 409 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 →

Effects of Intermittent Versus Continuous Energy Intakes on Insulin Sensitivity and Metabolic Risk in Women with Overweight.

Objective: This study aimed to compare intermittent fasting (IF) versus continuous energy intakes at 100% or 70% of calculated energy requirements on insulin sensitivity, cardiometabolic risk, body weight, and composition. Methods: Women with overweight (n = 88; 50 ± 1 years, BMI 32.3 ± 0.5 kg/m2 ) were randomized to one of four diets (IF70, IF100, dietary restriction [DR70], or control) in a 2:2:2:1 ratio for 8 weeks. IF groups fasted for 24 hours after breakfast on three nonconsecutive days per week. All foods were provided and diets matched for macronutrient composition (35% fat, 15% protein, 50% carbohydrate). Insulin sensitivity by hyperinsulinemic-euglycemic clamp, weight, body composition, and plasma markers were assessed following a "fed" day (12-hour fast) and a 24-hour fast (IF only). Results: IF70 displayed greater reductions in weight, fat mass, total- and low-density lipoprotein cholesterol, and nonesterified fatty acids compared with DR70 and IF100 (all P ≤ 0.05). IF100 lost more weight and fat than control. However, fasting insulin was increased. There were no group differences in insulin sensitivity by clamp; however, a 24-hour fast transiently reduced insulin sensitivity. Conclusions: When prescribed at matched energy restriction, IF reduced weight and fat mass and improved total and low-density lipoprotein cholesterol more than DR. IF prescribed in energy balance did not improve health compared with other groups, despite modest weight loss.

Obesity (Silver Spring, Md.) · 94 citationsread the source →

Pharmacotherapies for sleep disturbances in dementia.

Background: Sleep disturbances, including reduced nocturnal sleep time, sleep fragmentation, nocturnal wandering, and daytime sleepiness are common clinical problems in dementia, and are associated with significant caregiver distress, increased healthcare costs, and institutionalisation. Drug treatment is often sought to alleviate these problems, but there is significant uncertainty about the efficacy and adverse effects of the various hypnotic drugs in this vulnerable population. Objectives: To assess the effects, including common adverse effects, of any drug treatment versus placebo for sleep disorders in people with dementia, through identification and analysis of all relevant randomised controlled trials (RCTs). Search methods: We searched ALOIS (www.medicine.ox.ac.uk/alois), the Cochrane Dementia and Cognitive Improvement Group's Specialized Register, in March 2013 and again in March 2016, using the terms: sleep, insomnia, circadian, hypersomnia, parasomnia, somnolence, rest-activity, sundowning. Selection criteria: We included RCTs that compared a drug with placebo, and that had the primary aim of improving sleep in people with dementia who had an identified sleep disturbance at baseline. Trials could also include non-pharmacological interventions, as long as both drug and placebo groups had the same exposure to them. Data collection and analysis: Two review authors independently extracted data on study design, risk of bias, and results from the included study reports. We obtained additional information from study authors where necessary. We used the mean difference as the measure of treatment effect, and where possible, synthesized results using a fixed-effect model. Main results: We found six RCTs eligible for inclusion for three drugs: melatonin (222 participants, four studies, but only two yielded data on our primary sleep outcomes suitable for meta-analysis), trazodone (30 participants, one study), and ramelteon (74 participants, one study, no peer-reviewed publication, limited information available).The participants in the trazodone study and almost all participants in the melatonin studies had moderate-to-severe dementia due to Alzheimer's disease (AD); those in the ramelteon study had mild-to-moderate AD. Participants had a variety of common sleep problems at baseline. All primary sleep outcomes were measured using actigraphy. In one study of melatonin, drug treatment was combined with morning bright light therapy. Only two studies made a systematic assessment of adverse effects. Overall, the evidence was at low risk of bias, although there were areas of incomplete reporting, some problems with participant attrition, related largely to poor tolerance of actigraphy and technical difficulties, and a high risk of selective reporting in one trial that contributed very few participants. The risk of bias in the ramelteon study was unclear due to incomplete reporting. We found no evidence that melatonin, at doses up to 10 mg, improved any major sleep outcome over 8 to 10 weeks in patients with AD who were identified as having a sleep disturbance. We were able to synthesize data for two of our primary sleep outcomes: total nocturnal sleep time (mean difference (MD) 10.68 minutes, 95% CI -16.22 to 37.59; N = 184; two studies), and the ratio of daytime sleep to night-time sleep (MD -0.13, 95% CI -0.29 to 0.03; N = 184; two studies). From single studies, we found no difference between melatonin and placebo groups for sleep efficiency, time awake after sleep onset, or number of night-time awakenings. From two studies, we found no effect of melatonin on cognition or performance of activities of daily living (ADL). No serious adverse effects of melatonin were reported in the included studies. We considered this evidence to be of low quality. There was low-quality evidence that trazodone 50 mg given at night for two weeks improved total nocturnal sleep time (MD 42.46 minutes, 95% CI 0.9 to 84.0; N = 30; one study), and sleep efficiency (MD 8.53%, 95% CI 1.9 to 15.1; N = 30; one study) in patients with moderate-to-severe AD, but it did not affect the amount of time spent awake after sleep onset (MD -20.41, 95% CI -60.4 to 19.6; N = 30; one study), or the number of nocturnal awakenings (MD -3.71, 95% CI -8.2 to 0.8; N = 30; one study). No effect was seen on daytime sleep, cognition, or ADL. No serious adverse effects of trazodone were reported. Results from a phase 2 trial investigating ramelteon 8 mg administered at night were available in summary form in a sponsor's synopsis. Because the data were from a single, small study and reporting was incomplete, we considered this evidence to be of low quality in general terms. Ramelteon had no effect on total nocturnal sleep time at one week (primary outcome) or eight weeks (end of treatment) in patients with mild-to-moderate AD. The synopsis reported few significant differences from placebo for any sleep, behavioural, or cognitive outcomes; none were likely to be of clinical significance. There were no serious adverse effects from ramelteon. Authors' conclusions: We discovered a distinct lack of evidence to help guide drug treatment of sleep problems in dementia. In particular, we found no RCTs of many drugs that are widely prescribed for sleep problems in dementia, including the benzodiazepine and non-benzodiazepine hypnotics, although there is considerable uncertainty about the balance of benefits and risks associated with these common treatments. From the studies we identified for this review, we found no evidence that melatonin (up to 10mg) helped sleep problems in patients with moderate to severe dementia due to AD. There was some evidence to support the use of a low dose (50 mg) of trazodone, although a larger trial is needed to allow a more definitive conclusion to be reached on the balance of risks and benefits. There was no evidence of any effect of ramelteon on sleep in patients with mild to moderate dementia due to AD. This is an area with a high need for pragmatic trials, particularly of those drugs that are in common clinical use for sleep problems in dementia. Systematic assessment of adverse effects is essential.

The Cochrane database of systematic reviews · meta-analysis · 64 citationsread the source →

Psychological therapies for people with borderline personality disorder.

Background: Borderline personality disorder (BPD) is a relatively common personality disorder with a major impact on health services as those affected often present in crisis, often self-harming. Objectives: To evaluate the effects of psychological interventions for people with borderline personality disorder. Search strategy: We conducted a systematic search of 26 specialist and general bibliographic databases (December 2002) and searched relevant reference lists for further trials. Selection criteria: All relevant clinical randomised controlled trials involving psychological treatments for people with BPD. The definition of psychological treatments included behavioural, cognitive-behavioural, psychodynamic and psychoanalytic. Data collection and analysis: We independently selected, quality assessed and data extracted studies. For binary outcomes we calculated a standard estimation of the risk ratio (RR), its 95% confidence interval (CI), and where possible the number need to help/harm (NNT/H). For continuous outcomes, endpoint data were preferred to change data. Non-skewed data from valid scales were summated using a weighted mean difference (WMD). Main results: We identified seven studies involving 262 people, and five separate comparisons. Comparing dialectical behaviour therapy (DBT) with treatment as usual studies found no difference for the outcome of still meeting SCID-II criteria for the diagnosis of BPD by six months (n=28, 1 RCT, RR 0.69 CI 0.35 to 1.38) or admission to hospital in previous three months (n=28, 1 RCT, RR 0.77 CI 0.28 to 2.14). Self harm or parasuicide may decrease at 6 to 12 months (n=63, 1 RCT, RR 0.81 CI 0.66 to 0.98, NNT 12 CI 7 to 108). One study detected statistical difference in favour of people receiving DBT compared with those allocated to treatment as usual for average scores of suicidal ideation at 6 months (n=20, MD -15.30 CI -25.46 to -5.14). There was no difference for the outcome of leaving the study early (n=155, 3 RCTs, RR 0.74 CI 0.52 to 1.04). For the outcome of interviewer-assessed alcohol free days, skewed data are reported and tend to favour DBT. When a substance abuse focused DBT was compared with comprehensive validation therapy plus 12-step substance misuse programme no clear differences were found for service outcomes (n=23, 1 RCT, RR imprisoned 1.09 CI 0.64 to 1.87) or leaving the study early (n=23, 1 RCT, RR 7.58 CI 0.44 to 132.08). When dialectical behaviour therapy-oriented treatment is compared with client centred therapy no differences were found for service outcomes (n=24, 1 RCT, RR admitted 0.33 CI 0.08 to 1.33). However, fewer people in the DBT group displayed indicators of parasuicidal behaviour (n=24, RR 0.13 CI 0.02 to 0.85, NNT 2 CI 2 to 11). There were no differences for outcomes of anxiety and depression (n=24, 1 RCT, RR anxiety BAI >/=10 0.60 CI 0.32 to 1.12; RR depression HDRS >/=10 0.43 CI 0.14 to 1.28) but people who received DBT had less general psychiatric severity than those in the control (MD BPRS at 6 months -7.41 CI -13.72 to -1.10). Finally this one relevant study reports skewed data for suicidal ideation with considerably lower scores for people allocated to DBT. When psychoanalytically oriented partial hospitalization was compared with general psychiatric care the former tended to come off best. People who received treatment in a psychoanalytic orientated day hospital were less likely to be admitted into inpatient care when measured at different time points (e.g. n=44, RR admitted to inpatient 24 hour care >18 to 24 months 0.05 CI 0.00 to 0.77, NNT 3 CI 3 to 10) Fewer people in psychoanalytically oriented partial hospitalization needed day hospital intervention in the 18 months after discharge (n=44, 1 RCT, RR 0.04 CI 0.00 to 0.59, NNT 2 CI 2 to 8). More people in the control group took psychotropic medication by the 30 to 36 month follow-up, than those receiving psychoanalytic treatment (n=44, 1 RCT, RR 0.44 CI 0.25 to 0.80, NNT 3 CI 2 to 7). Anxiety and depression scores were generally lower in the psychoanalytically oriented partial hospitalization group (n=44, 1 RCT, RR >/=14 on BDI 0.52 CI 0.34 to 0.80, NNT 3 CI 3 to 6), as are global severity scores. People receiving psychoanalytic care in a day hospital had better social improvement in social adjustment using the SAS-SR at 6 to 12 months compared with people in general psychiatric care (MD -0.70 CI -1.08 to -0.32). Rates of attrition were the same (n=44, 1 RCT, RR leaving the study early 1.00 CI 0.23 to 4.42). Authors' conclusions: This review suggests that some of the problems frequently encountered by people with borderline personality disorder may be amenable to talking/behavioural treatments but all therapies remain experimental and the studies are too few and small to inspire full confidence in their results. These findings require replication in larger 'real-world' studies.

The Cochrane database of systematic reviews · meta-analysis · 52 citationsread the source →

Physical activity behaviour change in people living with and beyond cancer following an exercise intervention: a systematic review.

Purpose: Exercise interventions can increase physical activity and wellbeing of people living with/beyond cancer. However, little is known about maintenance of physical activity in this population ≥ 6 months post-exercise intervention, when theoretical evidence suggests behaviour maintenance occurs. Study aims are to (i) systematically review maintenance of physical activity ≥ 6-month post-exercise intervention, and (ii) investigate the influence of behaviour change techniques (BCTs) on physical activity maintenance in people living with/beyond cancer. Methods: CINAHL, CENTRAL, EMBASE and PubMed databases were searched for randomised controlled trials up to August 2021. Trials including adults diagnosed with cancer that assessed physical activity ≥ 6 months post-exercise intervention were included. Results: Of 142 articles assessed, 21 reporting on 18 trials involving 3538 participants were eligible. Five (21%) reported significantly higher physical activity ≥ 6 months post-exercise intervention versus a control/comparison group. Total number of BCTs (M = 8, range 2-13) did not influence intervention effectiveness. The BCTs Social support, Goal setting (behaviour), and Action planning, alongside supervised exercise, were important, but not sufficient, components for long-term physical activity maintenance. Conclusions: Evidence for long-term physical activity maintenance post-exercise intervention for people living with/beyond cancer is limited and inconclusive. Further research is required to ensure the physical activity and health benefits of exercise interventions do not quickly become obsolete. Implications for cancer survivors: Implementation of the BCTs Social support, Goal setting (behaviour), and Action planning, alongside supervised exercise, may enhance physical activity maintenance and subsequent health outcomes in people living with/beyond cancer.

Journal of cancer survivorship : research and practice · systematic review · 20 citationsread the source →

An updated systematic review of interventions to increase awareness of mental health and well-being in athletes, coaches, officials and parents.

Background: Interventions designed to increase mental health awareness in sport have grown substantially in the last 5 years, meaning that those involved in policy, research and intervention implementation are not fully informed by the latest systematic evaluation of research, risking a disservice to healthcare consumers. Hence, our aim was to update a 2017 systematic review that determined the effect of sport-specific mental health awareness programmes to improve mental health knowledge and help-seeking among sports coaches, athletes and officials. We extended the review to incorporate parents as a source of help-seeking and report the validity of outcome measures and quality of research design that occurred since the original review. Methods: Sport-specific mental health awareness programmes adopting an experimental or quasi-experimental design were included for synthesis. Five electronic databases were searched: Psychinfo, Medline (OVID interface), Scopus, Cochrane and Cinahl. Each database was searched from its year of inception to June 2020. As all of the outcomes measured were derived from psychometric scales, we observed statistically significant quantitative effects on the basis of p < .05, and a small, medium or large effect size as d = .2, .5 or .8, respectively. Risk of bias was assessed using the Cochrane and QATSQ tools. Results: Twenty-eight articles were included from the 2048 retrieved, eighteen additional articles since the original review. Eighteen studies targeted athletes, five with coaches, one sport officials (i.e. referees), one 'at-risk children' and three with parents. One of the studies was a combination of athletes, coaches and parents. In terms of study outcomes, health referral efficacy was improved in seven studies; twelve studies reported an increase in knowledge about mental health disorders. Proportionally, higher quality research designs were evident, as three of ten studies within the previous review did not demonstrate a high risk of bias, whereas thirteen of the eighteen additional studies did not display a high risk of bias. However, only one study included a behaviour change model in both the programme design and evaluation. Conclusions: Our updated systematic review provides evidence of the benefits of mental health awareness interventions in sport; these benefits are mainly for athletes and show improvements in the methodological design of recent studies compared to the first review. There was also evidence of the extension of programme delivery to parents. In conclusion, researchers, practitioners and policy makers should consider methodological guidance and the application of theory when developing and evaluating complex interventions. Systematic review registration: PROSPERO CRD42016040178.

Systematic reviews · systematic review · 32 citationsread the source →

The neighborhood social environment and physical activity: a systematic scoping review.

Background: Investigating the association of the neighborhood social environment on physical activity is complex. A systematic scoping review was performed to (1) provide an inventory of studies assessing the influence of the neighborhood social environment on physical activity since 2006; (2) describe methodologies employed; and (3) formulate recommendations for the field. Methods: Two databases were searched using terms related to 'physical activity,' 'neighborhood,' and 'social environment' in January 2017. Eligibility criteria included: 1) physical activity as an outcome; 2) neighborhood social environment as a predictor; 3) healthy population (without diagnosed clinical condition or special population); 4) observational or experimental design. Of 1352 studies identified, 181 were included. Textual data relevant to the social environment measurement and analysis were extracted from each article into qualitative software (MAXQDA) and coded to identify social environmental constructs, measurement methods, level of measurement (individual vs. aggregated to neighborhood), and whether authors explicitly recognized the construct as the social environment. The following measures were generated for each construct: number of unique measurements; % of times measured at an aggregate level; % of times authors referred to the construct as the social environment. Social environmental constructs were then grouped into larger descriptive dimensions. Results/findings: Fifty-nine social environmental constructs were identified and grouped into 9 dimensions: Crime & Safety (n = 133 studies; included in 73% of studies); Economic & Social Disadvantage (n = 55, 33%); Social Cohesion & Capital (n = 47, 26%); Social Relationships (n = 22, 12%); Social Environment (n = 16, 9%); Disorder & Incivilities (n = 15, 8%); Sense of Place/Belonging (n = 8, 4%); Discrimination/Segregation (n = 3, 2%); Civic Participation & Engagement (n = 2, 1%). Across all articles, the social environment was measured using 176 different methods, was measured at an aggregate-level 38% of the time, and referred to as the social environment 23% of the time. Conclusions: Inconsistent terminology, definitions, and measurement of the social environment and the lack of explicit language identifying constructs as the social environment make it challenging to compare results across studies and draw conclusions. Improvements are needed to increase our understanding of social environmental correlates and/or determinants of physical activity and facilitate cross-disciplinary conversations necessary to effectively intervene to promote physical activity. Trial registration: PROSPERO CRD42017059580.

The international journal of behavioral nutrition and physical activity · review · 81 citationsread the source →

Interventions to support the resilience and mental health of frontline health and social care professionals during and after a disease outbreak, epidemic or pandemic: a mixed methods systematic review.

Background: Evidence from disease epidemics shows that healthcare workers are at risk of developing short- and long-term mental health problems. The World Health Organization (WHO) has warned about the potential negative impact of the COVID-19 crisis on the mental well-being of health and social care professionals. Symptoms of mental health problems commonly include depression, anxiety, stress, and additional cognitive and social problems; these can impact on function in the workplace. The mental health and resilience (ability to cope with the negative effects of stress) of frontline health and social care professionals ('frontline workers' in this review) could be supported during disease epidemics by workplace interventions, interventions to support basic daily needs, psychological support interventions, pharmacological interventions, or a combination of any or all of these. Objectives: Objective 1: to assess the effects of interventions aimed at supporting the resilience and mental health of frontline health and social care professionals during and after a disease outbreak, epidemic or pandemic. Objective 2: to identify barriers and facilitators that may impact on the implementation of interventions aimed at supporting the resilience and mental health of frontline health and social care professionals during and after a disease outbreak, epidemic or pandemic. Search methods: On 28 May 2020 we searched the Cochrane Database of Systematic Reviews, CENTRAL, MEDLINE, Embase, Web of Science, PsycINFO, CINAHL, Global Index Medicus databases and WHO Institutional Repository for Information Sharing. We also searched ongoing trials registers and Google Scholar. We ran all searches from the year 2002 onwards, with no language restrictions. Selection criteria: We included studies in which participants were health and social care professionals working at the front line during infectious disease outbreaks, categorised as epidemics or pandemics by WHO, from 2002 onwards. For objective 1 we included quantitative evidence from randomised trials, non-randomised trials, controlled before-after studies and interrupted time series studies, which investigated the effect of any intervention to support mental health or resilience, compared to no intervention, standard care, placebo or attention control intervention, or other active interventions. For objective 2 we included qualitative evidence from studies that described barriers and facilitators to the implementation of interventions. Outcomes critical to this review were general mental health and resilience. Additional outcomes included psychological symptoms of anxiety, depression or stress; burnout; other mental health disorders; workplace staffing; and adverse events arising from interventions. Data collection and analysis: Pairs of review authors independently applied selection criteria to abstracts and full papers, with disagreements resolved through discussion. One review author systematically extracted data, cross-checked by a second review author. For objective 1, we assessed risk of bias of studies of effectiveness using the Cochrane 'Risk of bias' tool. For objective 2, we assessed methodological limitations using either the CASP (Critical Appraisal Skills Programme) qualitative study tool, for qualitative studies, or WEIRD (Ways of Evaluating Important and Relevant Data) tool, for descriptive studies. We planned meta-analyses of pairwise comparisons for outcomes if direct evidence were available. Two review authors extracted evidence relating to barriers and facilitators to implementation, organised these around the domains of the Consolidated Framework of Implementation Research, and used the GRADE-CERQual approach to assess confidence in each finding. We planned to produce an overarching synthesis, bringing quantitative and qualitative findings together. Main results: We included 16 studies that reported implementation of an intervention aimed at supporting the resilience or mental health of frontline workers during disease outbreaks (severe acute respiratory syndrome (SARS): 2; Ebola: 9; Middle East respiratory syndrome (MERS): 1; COVID-19: 4). Interventions studied included workplace interventions, such as training, structure and communication (6 studies); psychological support interventions, such as counselling and psychology services (8 studies); and multifaceted interventions (2 studies). Objective 1: a mixed-methods study that incorporated a cluster-randomised trial, investigating the effect of a work-based intervention, provided very low-certainty evidence about the effect of training frontline healthcare workers to deliver psychological first aid on a measure of burnout. Objective 2: we included all 16 studies in our qualitative evidence synthesis; we classified seven as qualitative and nine as descriptive studies. We identified 17 key findings from multiple barriers and facilitators reported in studies. We did not have high confidence in any of the findings; we had moderate confidence in six findings and low to very low confidence in 11 findings. We are moderately confident that the following two factors were barriers to intervention implementation: frontline workers, or the organisations in which they worked, not being fully aware of what they needed to support their mental well-being; and a lack of equipment, staff time or skills needed for an intervention. We are moderately confident that the following three factors were facilitators of intervention implementation: interventions that could be adapted for local needs; having effective communication, both formally and socially; and having positive, safe and supportive learning environments for frontline workers. We are moderately confident that the knowledge or beliefs, or both, that people have about an intervention can act as either barriers or facilitators to implementation of the intervention. Authors' conclusions: There is a lack of both quantitative and qualitative evidence from studies carried out during or after disease epidemics and pandemics that can inform the selection of interventions that are beneficial to the resilience and mental health of frontline workers. Alternative sources of evidence (e.g. from other healthcare crises, and general evidence about interventions that support mental well-being) could therefore be used to inform decision making. When selecting interventions aimed at supporting frontline workers' mental health, organisational, social, personal, and psychological factors may all be important. Research to determine the effectiveness of interventions is a high priority. The COVID-19 pandemic provides unique opportunities for robust evaluation of interventions. Future studies must be developed with appropriately rigorous planning, including development, peer review and transparent reporting of research protocols, following guidance and standards for best practice, and with appropriate length of follow-up. Factors that may act as barriers and facilitators to implementation of interventions should be considered during the planning of future research and when selecting interventions to deliver within local settings.

The Cochrane database of systematic reviews · meta-analysis · 415 citationsread the source →

Health of men, women, and children in post-trafficking services in Cambodia, Thailand, and Vietnam: an observational cross-sectional study.

Background: Trafficking is a crime of global proportions involving extreme forms of exploitation and abuse. Yet little research has been done of the health risks and morbidity patterns for men, women, and children trafficked for various forms of forced labour. Methods: We carried out face-to-face interviews with a consecutive sample of individuals entering 15 post-trafficking services in Cambodia, Thailand, and Vietnam. We asked participants about living and working conditions, experience of violence, and health outcomes. We measured symptoms of anxiety and depression with the Hopkins Symptoms Checklist and post-traumatic stress disorder with the Harvard Trauma Questionnaire, and used adjusted logistic regression models to estimate the effect of trafficking on these mental health outcomes, controlling for age, sector of exploitation, and time in trafficking. Findings: We interviewed 1102 people, of whom 1015 reached work destinations. Participants worked in various sectors including sex work (329 [32%]), fishing (275 [27%]), and factories (136 [13%]). 481 (48%) of 1015 experienced physical violence, sexual violence, or both, with 198 (35%) of 566 women and girls reporting sexual violence. 478 (47%) of 1015 participants were threatened and 198 (20%) were locked in a room. 685 (70%) of 985 who had data available worked 7 days per week and 296 (30%) of 989 worked at least 11 hours per day. 222 (22%) of 983 had a serious injury at work. 61·2% (95% CI 58·2-64·2) of participants reported symptom of depression, 42·8% (39·8-45·9) reported symptoms of anxiety, and 38·9% (36·0-42·0) reported symptoms of post-traumatic stress disorder. 5·2% (4·0-6·8) had attempted suicide in the past month. Participants who experienced extremely excessive overtime at work, restricted freedom, bad living conditions, threats, or severe violence were more likely to report symptoms of depression, anxiety, and post-traumatic stress disorder. Interpretation: This is the first health study of a large and diverse sample of men, women, and child survivors of trafficking for various forms of exploitation. Violence and unsafe working conditions were common and psychological morbidity was associated with severity of abuse. Survivors of trafficking need access to health care, especially mental health care. Funding: Anesvad Foundation and International Organization for Migration International Development Fund.

The Lancet. Global health · 87 citationsread the source →

Web-Based STAR E-Learning Course Increases Empathy and Understanding in Dementia Caregivers: Results from a Randomized Controlled Trial in the Netherlands and the United Kingdom.

Background: The doubling of the number of people with dementia in the coming decades coupled with the rapid decline in the working population in our graying society is expected to result in a large decrease in the number of professionals available to provide care to people with dementia. As a result, care will be supplied increasingly by untrained informal caregivers and volunteers. To promote effective care and avoid overburdening of untrained and trained caregivers, they must become properly skilled. To this end, the European Skills Training and Reskilling (STAR) project, which comprised experts from the domains of education, technology, and dementia care from 6 countries (the Netherlands, Sweden, Italy, Malta, Romania, and the United Kingdom), worked together to create and evaluate a multilingual e-learning tool. The STAR training portal provides dementia care training both for informal and formal caregivers. Objective: The objective of the current study was to evaluate the user friendliness, usefulness, and impact of STAR with informal caregivers, volunteers, and professional caregivers. Methods: For 2 to 4 months, the experimental group had access to the STAR training portal, a Web-based portal consisting of 8 modules, 2 of which had a basic level and 6 additional modules at intermediate and advanced levels. The experimental group also had access to online peer and expert communities for support and information exchange. The control group received free access to STAR after the research had ended. The STAR training portal was evaluated in a randomized controlled trial among informal caregivers and volunteers in addition to professional caregivers (N=142) in the Netherlands and the United Kingdom. Assessments were performed with self-assessed, online, standardized questionnaires at baseline and after 2 to 4 months. Primary outcome measures were user friendliness, usefulness, and impact of STAR on knowledge, attitudes, and approaches of caregivers regarding dementia. Secondary outcome measures were empathy, quality of life, burden, and caregivers' sense of competence. Results: STAR was rated positively by all user groups on both usefulness and user friendliness. Significant effects were found on a person-centered care approach and on the total score on positive attitudes to dementia; both the experimental and the control group increased in score. Regarding empathy, significant improvements were found in the STAR training group on distress, empathic concern, and taking the perspective of the person with dementia. In the experimental group, however, there was a significant reduction in self-reported sense of competence. Conclusions: The STAR training portal is a useful and user-friendly e-learning method, which has demonstrated its ability to provide significant positive effects on caregiver attitudes and empathy.

Journal of medical Internet research · randomised controlled trial · 117 citationsread the source →

3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial.

Background: Post-traumatic stress disorder (PTSD) is prevalent in military personnel and first responders, many of whom do not respond to currently available treatments. This study aimed to assess the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treating chronic PTSD in this population. Methods: We did a randomised, double-blind, dose-response, phase 2 trial at an outpatient psychiatric clinic in the USA. We included service personnel who were 18 years or older, with chronic PTSD duration of 6 months or more, and who had a Clinician-Administered PTSD Scale (CAPS-IV) total score of 50 or greater. Using a web-based randomisation system, we randomly assigned participants (1:1:2) to three different dose groups of MDMA plus psychotherapy: 30 mg (active control), 75 mg, or 125 mg. We masked investigators, independent outcome raters, and participants until after the primary endpoint. MDMA was administered orally in two 8-h sessions with concomitant manualised psychotherapy. The primary outcome was mean change in CAPS-IV total score from baseline to 1 month after the second experimental session. Participants in the 30 mg and 75 mg groups subsequently underwent three 100-125 mg MDMA-assisted psychotherapy sessions in an open-label crossover, and all participants were assessed 12 months after the last MDMA session. Safety was monitored through adverse events, spontaneously reported expected reactions, vital signs, and suicidal ideation and behaviour. This study is registered with ClinicalTrials.gov, number NCT01211405. Findings: Between Nov 10, 2010, and Jan 29, 2015, 26 veterans and first responders met eligibility criteria and were randomly assigned to receive 30 mg (n=7), 75 mg (n=7), or 125 mg (n=12) of MDMA plus psychotherapy. At the primary endpoint, the 75 mg and 125 mg groups had significantly greater decreases in PTSD symptom severity (mean change CAPS-IV total scores of -58·3 [SD 9·8] and -44·3 [28·7]; p=0·001) than the 30 mg group (-11·4 [12·7]). Compared with the 30 mg group, Cohen's d effect sizes were large: 2·8 (95% CI 1·19-4·39) for the 75 mg group and 1·1 (0·04-2·08) for the 125 mg group. In the open-label crossover with full-dose MDMA (100-125 mg), PTSD symptom severity significantly decreased in the group that had previously received 30 mg (p=0·01), whereas no further significant decreases were observed in the group that previously achieved a large response after 75 mg doses in the blinded segment (p=0·81). PTSD symptoms were significantly reduced at the 12-month follow-up compared with baseline after all groups had full-dose MDMA (mean CAPS-IV total score of 38·8 [SD 28·1] vs 87·1 [16·1]; p<0·0001). 85 adverse events were reported by 20 participants. Of these adverse events, four (5%) were serious: three were deemed unrelated and one possibly related to study drug treatment. Interpretation: Active doses (75 mg and 125 mg) of MDMA with adjunctive psychotherapy in a controlled setting were effective and well tolerated in reducing PTSD symptoms in veterans and first responders. Funding: Multidisciplinary Association for Psychedelic Studies.

The lancet. Psychiatry · randomised controlled trial · 258 citationsread the source →

Evaluation of subjective effects of aripiprazole and methamphetamine in methamphetamine-dependent volunteers.

A variety of neuropharmacological strategies are being pursued in the search for an effective treatment for methamphetamine (Meth) addiction. In this study, we investigated the safety and potential efficacy of aripiprazole, an antipsychotic agent acting on both dopamine and serotonin systems. We conducted a double-blind in-patient clinical pharmacology study to assess potential interactions between intravenous (i.v.) Meth (15 mg and 30 mg) and oral aripiprazole (15 mg). In addition, the effects of aripiprazole treatment on abstinence-related craving and cue-induced craving were evaluated. Participants included non-treatment-seeking, Meth-dependent patients (n=16), aged 18-45 yr, currently using Meth. Following baseline Meth dosing (15 mg and 30 mg), participants received 2 wk treatment with aripiprazole (n=8) or placebo (n=8). Participants then completed cue exposure sessions using neutral and Meth-related cues. Meth dosing (15 mg and 30 mg) was then repeated. Aripiprazole treatment had no effect on cue-induced Meth craving, or on daily baseline craving assessed over the course of medication treatment, although aripiprazole treatment was associated with increased craving independent of Meth dosing. Aripiprazole treatment was associated with significantly higher ratings on Addiction Research Center Inventory (ARCI) subscales reflecting euphoria and amphetamine-like effects following Meth dosing. Aripiprazole treatment was also associated with significant reductions in ratings of 'bad effects' and reductions on the ARCI subscale for sedation effects following Meth dosing. Aripiprazole treatment reduced the increase in systolic blood pressure following Meth dosing, but had no other effects on cardiovascular responses to Meth. Aripiprazole treatment did not alter the pharmacokinetics of Meth. These findings indicate that aripiprazole treatment appears to be safe in volunteers with Meth dependence, although the finding that aripiprazole increased some of the rewarding and stimulatory effects produced by acute Meth suggests that 15 mg aripiprazole is unlikely to be efficacious for the treatment of Meth dependence. Further research with lower doses of aripiprazole, possibly using study designs aimed at evaluating efficacy for relapse prevention, are needed before ruling out aripiprazole as a treatment for Meth dependence.

The international journal of neuropsychopharmacology · randomised controlled trial · 37 citationsread the source →

Effect of a smartphone application (Perx) on medication adherence and clinical outcomes: a 12-month randomised controlled trial.

Objective: To determine whether the Perx app improves medication adherence and clinical outcomes over 12 months compared with standard care in patients requiring polypharmacy. Design: Randomised controlled trial with 12-month follow-up. Setting: Outpatient clinics in three tertiary hospitals in Sydney, Australia. Participants: Eligible participants were aged 18-75 years, with at least one chronic condition, taking ≥3 different medications (oral medications or injections), with smartphone accessibility. Participants were randomised in a 1:1 ratio. Interventions: The intervention group used the Perx app that contained customised reminders and gamified interactions to reward verified medication adherence. Main outcome measures: The primary outcome was medication adherence over 12 months measured using pill counts. Secondary outcomes included clinical outcomes (haemoglobin A1c (HbA1c), cholesterol, blood glucose, triglycerides, creatinine, thyroid function, blood pressure and weight). Results: Of 1412 participants screened for eligibility, 124 participants were randomised; 45 in the Perx arm and 40 in the control arm completed the study. The average age was 59.5, 58.9% were women, chronic conditions were cardiovascular disease (78%), type 2 diabetes (75%), obesity (65%) or other endocrine disorders (18%). On average, participants were taking six medications daily. The Perx group had greater improvements in adherence at month 2 (Coef. 8%; 95% CI 0.01 to 0.15), month 3 (Coef. 7%; 95% CI 0.00 to 0.14) and month 12 (Coef. 7%; 95% CI 0.00 to 0.13). The probability of HbA1c ≤6.5% was greater in the Perx group at months 9 and 12 and cholesterol (total and low-density lipoprotein cholesterol) was lower in the Perx group at month 3. The intervention was particularly effective for those with obesity, taking medications for diabetes and taking ≤4 medications. Conclusions: This study provides evidence that app-based behavioural change interventions can increase medication adherence and produce longer-term improvements in some clinical outcomes in adults managing multimorbidity. More trials are needed to build the evidence base. Trial registration number: ACTRN12617001285347.

BMJ open · randomised controlled trial · 33 citationsread the source →

An Internet-Based Mindfulness- and Compassion-Based Intercare Program for Reducing Parental Burnout: Randomized Controlled Trial.

Background: Parental burnout is an underrecognized syndrome characterized by emotional exhaustion, detachment from children, and reduced parental efficacy. It is associated with sleep disturbance, addictive behaviors, suicidal ideation, and increased risk of child neglect and family conflict. Despite its public health relevance, evidence-based interventions remain limited, particularly in low- and middle-income contexts. Objective: This study aims to evaluate the efficacy and safety of a mindfulness- and compassion-based intercare program for parental burnout (IBAP-BP)-designed to reduce burnout symptoms in teleworking mothers. Methods: A 3-arm randomized controlled trial (IBAP-BP, active control, and waitlist) was conducted across Chile (December 2022-March 2023) with a 9-month follow-up. Participants (N=593) were women aged 18 years or older, teleworking ≥1 day/week, and living with at least 1 child. Exclusion criteria were self-reported severe psychiatric disorders. Randomization was computer-generated and centrally concealed; data analysts were blinded. The IBAP-BP group attended 8 weekly 2-hour internet-based sessions plus daily home practice integrating mindfulness and compassion. The active control performed relaxation and reflective journaling matched for duration and structure. The primary outcome was parental burnout at 9 months measured using the average-item score of the Parental Burnout Assessment; secondary outcomes were mindfulness, balance of risks/resources, and adverse effects. Modified intention-to-treat analyses and multilevel structural models assessed effects over time. Results: Of 593 randomized participants, 343 contributed at least 1 postbaseline assessment and comprised the modified intention-to-treat sample. At 9 months, the prespecified primary analysis showed greater reductions in parental burnout for IBAP-BP compared with the waitlist (mean difference=0.62, 95% CI 0.09-1.14; Cohen d≈0.6, 95% CI 0.41-0.77). No significant difference was found between IBAP-BP and the active control, which showed transient improvements up to 3 months. Effects remained robust in sensitivity analyses. Self-reported adverse events were rare and mild across IBAP-BP and active control. Mediation analyses showed inconsistent associations between mindfulness facets and outcomes. Conclusions: The culturally adapted, internet-based IBAP-BP program was feasible, safe, and effective compared with the waitlist condition for reducing parental burnout in working mothers, with effects sustained over 9 months, although it did not demonstrate superiority over the active control at the primary end point. Internet-based mindfulness- and compassion-based interventions may offer scalable, equitable options for preventing and treating parental burnout in resource-limited settings.

Journal of medical Internet research · randomised controlled trialread the source →

Effect of Mindfulness-Based Stress Reduction vs Cognitive Behavioral Therapy or Usual Care on Back Pain and Functional Limitations in Adults With Chronic Low Back Pain: A Randomized Clinical Trial.

Importance: Mindfulness-based stress reduction (MBSR) has not been rigorously evaluated for young and middle-aged adults with chronic low back pain. Objective: To evaluate the effectiveness for chronic low back pain of MBSR vs cognitive behavioral therapy (CBT) or usual care. Design, setting, and participants: Randomized, interviewer-blind, clinical trial in an integrated health care system in Washington State of 342 adults aged 20 to 70 years with chronic low back pain enrolled between September 2012 and April 2014 and randomly assigned to receive MBSR (n = 116), CBT (n = 113), or usual care (n = 113). Interventions: CBT (training to change pain-related thoughts and behaviors) and MBSR (training in mindfulness meditation and yoga) were delivered in 8 weekly 2-hour groups. Usual care included whatever care participants received. Main outcomes and measures: Coprimary outcomes were the percentages of participants with clinically meaningful (≥30%) improvement from baseline in functional limitations (modified Roland Disability Questionnaire [RDQ]; range, 0-23) and in self-reported back pain bothersomeness (scale, 0-10) at 26 weeks. Outcomes were also assessed at 4, 8, and 52 weeks. Results: There were 342 randomized participants, the mean (SD) [range] age was 49.3 (12.3) [20-70] years, 224 (65.7%) were women, mean duration of back pain was 7.3 years (range, 3 months-50 years), 123 (53.7%) attended 6 or more of the 8 sessions, 294 (86.0%) completed the study at 26 weeks, and 290 (84.8%) completed the study at 52 weeks. In intent-to-treat analyses at 26 weeks, the percentage of participants with clinically meaningful improvement on the RDQ was higher for those who received MBSR (60.5%) and CBT (57.7%) than for usual care (44.1%) (overall P = .04; relative risk [RR] for MBSR vs usual care, 1.37 [95% CI, 1.06-1.77]; RR for MBSR vs CBT, 0.95 [95% CI, 0.77-1.18]; and RR for CBT vs usual care, 1.31 [95% CI, 1.01-1.69]). The percentage of participants with clinically meaningful improvement in pain bothersomeness at 26 weeks was 43.6% in the MBSR group and 44.9% in the CBT group, vs 26.6% in the usual care group (overall P = .01; RR for MBSR vs usual care, 1.64 [95% CI, 1.15-2.34]; RR for MBSR vs CBT, 1.03 [95% CI, 0.78-1.36]; and RR for CBT vs usual care, 1.69 [95% CI, 1.18-2.41]). Findings for MBSR persisted with little change at 52 weeks for both primary outcomes. Conclusions and relevance: Among adults with chronic low back pain, treatment with MBSR or CBT, compared with usual care, resulted in greater improvement in back pain and functional limitations at 26 weeks, with no significant differences in outcomes between MBSR and CBT. These findings suggest that MBSR may be an effective treatment option for patients with chronic low back pain. Trial registration: clinicaltrials.gov Identifier: NCT01467843.

JAMA · randomised controlled trial · 469 citationsread the source →

Effect of a behavioural intervention in obese pregnant women (the UPBEAT study): a multicentre, randomised controlled trial.

Background: Behavioural interventions might improve clinical outcomes in pregnant women who are obese. We aimed to investigate whether a complex intervention addressing diet and physical activity could reduce the incidence of gestational diabetes and large-for-gestational-age infants. Methods: The UK Pregnancies Better Eating and Activity Trial (UPBEAT) is a randomised controlled trial done at antenatal clinics in eight hospitals in multi-ethnic, inner-city locations in the UK. We recruited pregnant women (15-18 weeks plus 6 days of gestation) older than 16 years who were obese (BMI ≥30 kg/m(2)). We randomly assigned participants to either a behavioural intervention or standard antenatal care with an internet-based, computer-generated, randomisation procedure, minimising by age, ethnic origin, centre, BMI, and parity. The intervention was delivered once a week through eight health trainer-led sessions. Primary outcomes were gestational diabetes (diagnosed with an oral glucose tolerance test and by criteria from the International Association of Diabetes in Pregnancy Study Groups) and large-for-gestational-age infants (≥90th customised birthweight centile). Analysis was by intention to treat. This trial is registered with Current Controlled Trials, ISCRTN89971375. Recruitment and pregnancy outcomes are complete but childhood follow-up is ongoing. Findings: Between March 31, 2009, and June 2, 2014, we assessed 8820 women for eligibility and recruited 1555, with a mean BMI of 36·3 kg/m(2) (SD 4·8). 772 were randomly assigned to standard antenatal care and 783 were allocated the behavioural intervention, of which 651 and 629 women, respectively, completed an oral glucose tolerance test. Gestational diabetes was reported in 172 (26%) women in the standard care group compared with 160 (25%) in the intervention group (risk ratio 0·96, 95% CI 0·79-1·16; p=0·68). 61 (8%) of 751 babies in the standard care group were large for gestational age compared with 71 (9%) of 761 in the intervention group (1·15, 0·83-1·59; p=0·40). Thus, the primary outcomes did not differ between groups, despite improvements in some maternal secondary outcomes in the intervention group, including reduced dietary glycaemic load, gestational weight gain, and maternal sum-of-skinfold thicknesses, and increased physical activity. Adverse events included neonatal death (two in the standard care group and three in the intervention group) and fetal death in utero (ten in the standard care group and six in the intervention group). No maternal deaths were reported. Incidence of miscarriage (2% in the standard care group vs 2% in the intervention group), major obstetric haemorrhage (1% vs 3%), and small-for-gestational-age infants (≤5th customised birthweight centile; 6% vs 5%) did not differ between groups. Interpretation: A behavioural intervention addressing diet and physical activity in women with obesity during pregnancy is not adequate to prevent gestational diabetes, or to reduce the incidence of large-for-gestational-age infants. Funding: National Institute for Health Research, Guys and St Thomas' Charity, Chief Scientist Office Scotland, Tommy's Charity.

The lancet. Diabetes & endocrinology · randomised controlled trial · 465 citationsread the source →

Intermittent Fasting Improves Cardiometabolic Risk Factors and Alters Gut Microbiota in Metabolic Syndrome Patients.

Context: Intermittent fasting (IF) is an effective strategy to improve cardiometabolic health. Objective: The objective of this work is to examine the effects of IF on cardiometabolic risk factors and the gut microbiota in patients with metabolic syndrome (MS). Design and setting: A randomized clinical trial was conducted at a community health service center. Patients: Participants included adults with MS, age 30 to 50 years. Intervention: Intervention consisted of 8 weeks of "2-day" modified IF. Main outcome measure: Cardiometabolic risk factors including body composition, oxidative stress, inflammatory cytokines, and endothelial function were assessed at baseline and at 8 weeks. The diversity, composition, and functional pathways of the gut microbiota, as well as circulating gut-derived metabolites, were measured. Results: Thirty-nine patients with MS were included: 21 in the IF group and 18 in the control group. On fasting days, participants in the IF group reduced 69% of their calorie intake compared to nonfasting days. The 8-week IF significantly reduced fat mass, ameliorated oxidative stress, modulated inflammatory cytokines, and improved vasodilatory parameters. Furthermore, IF induced significant changes in gut microbiota communities, increased the production of short-chain fatty acids, and decreased the circulating levels of lipopolysaccharides. The gut microbiota alteration attributed to the IF was significantly associated with cardiovascular risk factors and resulted in distinct genetic shifts of carbohydrate metabolism in the gut community. Conclusion: IF induces a significant alteration of the gut microbial community and functional pathways in a manner closely associated with the mitigation of cardiometabolic risk factors. The study provides potential mechanistic insights into the prevention of adverse outcomes associated with MS.

The Journal of clinical endocrinology and metabolism · randomised controlled trial · 153 citationsread the source →

Group therapy processes and treatment outcomes in 2 couple-focused group interventions for breast cancer patients.

Background: There has been little attention paid to the role of therapeutic processes in group therapy outcomes for cancer patients participating in group. The goal was to evaluate the contribution of 3 group processes-group climate (conflict, engagement, and avoidance) working alliance and therapeutic realizations-to the outcomes of 2 couple-focused approaches to group treatment. Methods: Three hundred and two women with early stage breast cancer and their partners were randomized to one of 2 conditions: an 8-session enhanced couple-focused group (ECG) intervention or a couples' support group participated. Couples completed measures of depressive symptoms and well-being before and 6 months after group. Group process measures were completed after sessions 4 and 8. Results: Support group participants (both patients and partners) perceived higher engagement and less avoidance than ECG participants. Conflict, working alliance, and therapeutic realizations did not differ. Group engagement, working alliance, and therapeutic realizations increased, and group conflict decreased over the course of both treatments. Greater conflict was associated with more posttreatment anxiety and lower well-being, and engagement was associated with higher posttreatment well-being. Patients whose partners reported higher conflict reported greater posttreatment anxiety. Working alliance was associated with posttreatment anxiety for ECG patients and with well-being among participants whose partners reported higher working alliance. Conclusions: Fostering a positive group environment bolsters treatment efficacy for women with early stage breast cancer and their partners attending couple-focused groups. Facilitating the leader-member alliance bolsters treatment efficacy. Improving engagement with one member of a couple impacts the other member.

Psycho-oncology · randomised controlled trial · 7 citationsread the source →

Skilled Counseling in Enhancing Early and Exclusive Breastfeeding Rates: An Experimental Study in an Urban Population in India.

Objective: The study was conducted to evaluate the effect of breastfeeding counseling and breastfeeding support by trained counselors during the ante-natal period at health facility and post-natal period at home on breastfeeding practices during the first six months of life. Design: This was a randomized controlled study that compared the effect of counseling on breastfeeding during the first 6 months of life. Setting: study was done in a government medical college in northern India, which is situated in an urban area. Participants: 300 healthy pregnant women from an urban population attending the antenatal clinic at Jawaharlal Nehru Medical College, Aligarh Muslim University were recruited for the study. Intervention: Subjects were equally assigned randomly to the intervention (2 antenatal and 8 postpartum home counseling visits by the counselors) and control (non-counseling) group. Main outcome measures: Infant feeding practices including rates of initiation of the breastfeeding within one hour of birth; exclusive breastfeeding and bottle-feeding during the first 6 months of life. Results: Initiation of breastfeeding within one hour of birth was 73.4% in intervention group as compared to 33.6% in control group (P=0.001). More mothers in the intervention group (88.2%) were able to sustain exclusive breastfeeding rates at 6 months of age in comparison to the control group (50%) (OR 7.44, 95% CI 3.98-13.92). Conclusions: This study substantiates positive role of skilled counseling by a trained dedicated breastfeeding counselor during the antenatal and post-natal periods on breastfeeding practices during the first six months of life.

Indian pediatrics · randomised controlled trial · 15 citationsread the source →

Vitamin D and probiotic co-supplementation affects mental health, hormonal, inflammatory and oxidative stress parameters in women with polycystic ovary syndrome.

Objective: The aim of this study was to determine the effect of vitamin D and probiotic co-administration on mental health, hormonal, inflammatory and oxidative stress parameters in women with polycystic ovary syndrome (PCOS). Methods: This randomized, double-blinded, placebo-controlled clinical trial was carried out on 60 subjects, aged 18-40 years old. Subjects were randomly allocated to take either 50,000 IU vitamin D every 2 weeks plus 8 × 109 CFU/day probiotic (n = 30) or placebo (n = 30) for 12 weeks. Results: Vitamin D and probiotic co-supplementation, compared with the placebo, significantly improved beck depression inventory [β (difference in the mean of outcomes measures between treatment groups) - 0.58; 95% CI, - 1.15, - 0.02; P = 0.04], general health questionnaire scores (β - 0.93; 95% CI, - 1.78, - 0.08; P = 0.03) and depression, anxiety and stress scale scores (β - 0.90; 95% CI, - 1.67, - 0.13; P = 0.02). Vitamin D and probiotic co-supplementation was associated with a significant reduction in total testosterone (β - 0.19 ng/mL; 95% CI, - 0.28, - 0.10; P < 0.001), hirsutism (β - 0.95; 95% CI, - 1.39, - 0.51; P < 0.001), high-sensitivity C-reactive protein (hs-CRP) (β - 0.67 mg/L; 95% CI, - 0.97, - 0.38; P < 0.001) and malondialdehyde (MDA) levels (β - 0.25 μmol/L; 95% CI, - 0.40, - 0.10; P = 0.001), and a significant increase in total antioxidant capacity (TAC) (β 82.81 mmol/L; 95% CI, 42.86, 122.75; P < 0.001) and total glutathione (GSH) levels (β 40.42 μmol/L; 95% CI, 4.69, 76.19; P = 0.02), compared with the placebo. Conclusions: Overall, the co-administration of vitamin D and probiotic for 12 weeks to women with PCOS had beneficial effects on mental health parameters, serum total testosterone, hirsutism, hs-CRP, plasma TAC, GSH and MDA levels. Trial registration: This study was retrospectively registered in the Iranian website ( www.irct.ir ) for registration of clinical trials ( IRCT20170513033941N37 ).

Journal of ovarian research · randomised controlled trial · 109 citationsread the source →