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حَدَّثَنَا أَبُو بَكْرِ بْنُ أَبِي شَيْبَةَ، وَأَبُو سَعِيدٍ الأَشَجُّ جَمِيعًا عَنْ وَكِيعٍ، - قَالَ الأَشَجُّ حَدَّثَنَا وَكِيعٌ، - حَدَّثَنَا الأَعْمَشُ، عَنْ زِيَادِ بْنِ الْحُصَيْنِ أَبِي جَهْمَةَ، عَنْ أَبِي الْعَالِيَةِ، عَنِ ابْنِ عَبَّاسٍ، قَالَ ‏{‏ مَا كَذَبَ الْفُؤَادُ مَا رَأَى‏}‏ ‏{‏ وَلَقَدْ رَآهُ نَزْلَةً أُخْرَى‏}‏ قَالَ رَآهُ بِفُؤَادِهِ مَرَّتَيْنِ ‏.‏

It is narrated on the authority of Ibn Abbas that the words:" The heart belied not what he saw" (al-Qur'an, Iiii. 11) and" Certainly he saw Him in another descent" (al-Qur'an, Iiii. 13) imply that he saw him twice with his heart

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Agro-waste derived compounds (flax and black seed peels): Toxicological effect against the West Nile virus vector, Culex pipiens L. with special reference to GC-MS analysis.

The development of different approaches to use agricultural residues as a source of high value-added products, become a must, especially after the problems emerged due to their accumulation. This contribution demonstrates the potential of agricultural residues, Linuim usitatissium (flax seed) and Nigella sativa (black seed) peels, as raw materials for the production of bioactive products, botanical insecticides, against Cx. pipiens, with deep analysis to their chemical constituents by gas chromatography-mass spectrometry, the larvicidal efficacies of the three crude extracts (methylene chloride, petroleum ether and methanol 70%) from the two plant waste peels were evaluated for the first time against the late third instar larvae of Cx. pipiens. Results indicated different lethal doses in larvae depending on the efficacy of organic solvent used. For both compounds methanol 70% extracts produced the highest dry yield. The most efficient solvent is petroleum ether in case of both flax and Black seed peels. Petroleum ether extract exhibited the highest toxicity against Cx. pipiens with an LC50 of 69.6383 ppm. The same results for black seed indicated that petroleum ether was the most efficient against Cx. pipiens with an LC50 of 40.7748 ppm. The study revealed for the first time the type of phytochemical constituents presents in peels of flax and black seeds using GC-MS analysis which revealed twenty-eight constituents among extracts of flax and black seed peels ranging from to 58.8711% to 99.99% of the total extracts. GC-MS profiling showed that a five constituents, 9-2-Methyl-Z, Z-3, 13 octadecadienol (terpenoid), 9,17-Octadecadienal, (Z)-, Nonanoic acid, 9-oxo-, methyl ester, 9,12-Octadecadienoic acid Z,Z and Octasiloxane, 1,1,3,3,5,5,7,7,9,9,11,11,13,13,15,15-hexadecamethyl- have insecticidal activity beside many other biological activities as recorded from a variety of botanical extracts. While the constituents like Hexadecanoic acid, methyl ester and cis-9-Hexadecenal, both of them are larvicidal, cis-Vaccenic acid and 9-Oxononanoic acid showing only an insecticidal activity beside Undecanoic acid the mosquito repellent. The other six constituents Linoelaidic acid, Oleic Acid, Z-2-Octadecen-1-ol, 1-Methoxy-3-hydroxymethylheptane, Cis-11,14-Eicosadieonic acid-methyl ester and Heptasiloxane, 1,1,3,3,5,5,7,7,9,9,11,11,13,13-tetradecamethyl- are constituents of other plant extracts which showed as a whole an insecticidal activity.

Saudi journal of biological sciences · 9 citationsread the source →

Outcome of children less than three years old at diagnosis with non-metastatic medulloblastoma treated with chemotherapy on the "Head Start" I and II protocols.

Purpose: To determine the survival of infants and young children with non-metastatic medulloblastoma using intensive myeloablative chemotherapy and autologous hematopoietic progenitor cell rescue (AuHCR). Methods: Twenty-one children less than 3 years old at diagnosis with non-metastatic medulloblastoma were enrolled on two identical serial studies, "Head Start" I and "Head Start" II. After surgery, patients received five cycles of induction chemotherapy consisting of vincristine, cisplatin, cyclophosphamide and etoposide. Following induction, all patients underwent myeloablative chemotherapy using carboplatin, thiotepa and etoposide with AuHCR. Irradiation was used only at relapse. Results: The 5-year event-free (EFS) and overall survival (OS) rates (+/-SE) for all patients, patients with gross total resection, and patients with residual tumor were 52 +/- 11% and 70 +/- 10%, 64 +/- 13% and 79 +/- 11%, and 29 +/- 17% and 57 +/- 19%, respectively. The 5-year EFS and OS ( +/- SE) for patients with desmoplastic and classical medulloblastoma were 67 +/- 16% and 78 +/- 14%, and 42 +/- 14 and 67 +/- 14%, respectively. There were four treatment related deaths. The majority of survivors (71%) avoided irradiation completely. Mean intellectual functioning and quality of life (QoL) for children surviving without irradiation was within average range for a majority of survivors tested. Conclusion: This strategy of brief intensive chemotherapy for young children with non-metastatic medulloblastoma eliminated the need for craniospinal irradiation 52% of the patients, and may preserve QoL and intellectual functioning. The excellent survival rates are somewhat dampened by high toxic mortality.

Pediatric blood & cancer · randomised controlled trial · 155 citationsread the source →

Effects of subcutaneous tirzepatide versus placebo or semaglutide on pancreatic islet function and insulin sensitivity in adults with type 2 diabetes: a multicentre, randomised, double-blind, parallel-arm, phase 1 clinical trial.

Background: Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, shows a remarkable ability to lower blood glucose, enabling many patients with long-standing type 2 diabetes to achieve normoglycaemia. We aimed to understand the physiological mechanisms underlying the action of tirzepatide in type 2 diabetes. Methods: This multicentre, randomised, double-blind, parallel-arm, phase 1 study was done at two centres in Germany. Eligible patients were aged 20-74 years, had type 2 diabetes for at least 6 months, and were being treated with lifestyle advice and stable doses of metformin, with or without one additional stable dose of another oral antihyperglycaemic medicine, 3 months before study entry. Via a randomisation table, patients were randomly assigned (3:3:2) to subcutaneously receive either tirzepatide 15 mg, semaglutide 1 mg, or placebo once per week. Endpoint measurements were done at baseline and the last week of therapy (week 28). The primary endpoint was the effect of tirzepatide versus placebo on the change in clamp disposition index (combining measures of insulin secretion and sensitivity) from baseline to week 28 of treatment and was analysed in the pharmacodynamic analysis set, which comprised all randomly assigned participants who received at least one dose of a study drug and had evaluable pharmacodynamic data. Safety was analysed in the safety population, which comprised all randomly assigned participants who received at least one dose of a study drug. Secondary endpoints included the effect of tirzepatide versus semaglutide on the change in clamp disposition index from baseline to week 28 of treatment, glucose control, total insulin secretion rate, M value (insulin sensitivity), and fasting and postprandial glucagon concentrations. Exploratory endpoints included the change in fasting and postprandial insulin concentrations. This study is registered with ClinicalTrials.gov, NCT03951753, and is complete. Findings: Between June 28, 2019, and April 8, 2021, we screened 184 individuals and enrolled 117 participants, all of whom were included in the safety population (45 in the tirzepatide 15 mg group, 44 in the semaglutide 1 mg group, and 28 in the placebo group). Because of discontinuations and exclusions due to missing or unevaluable data, 39 patients in each treatment group and 24 patients in the placebo group comprised the pharmacodynamic analysis set. With tirzepatide, the clamp disposition index increased from a least squares mean of 0·3 pmol m-2 L min-2 kg-1 (SE 0·03) at baseline by 1·9 pmol m-2 L min-2 kg-1 (0·16) to total 2·3 pmol m-2 L min-2 kg-1 (SE 0·16) at week 28 and, with placebo, the clamp disposition index did not change much from baseline (least squares mean at baseline 0·4 pmol m-2 L min-2 kg-1 [SE 0·04]; change from baseline 0·0 pmol m-2 L min-2 kg-1 [0·03]; least squares mean at week 28 0·3 [SE 0·03]; estimated treatment difference [ETD] tirzepatide vs placebo 1·92 [95% CI 1·59-2·24]; p<0·0001). The improvement with tirzepatide in clamp disposition index was significantly greater than with semaglutide (ETD 0·84 pmol m-2 L min-2 kg-1 [95% CI 0·46-1·21]). This result reflected significant improvements in total insulin secretion rate (ETD 102·09 pmol min-1 m-2 [51·84-152·33]) and insulin sensitivity (ETD 1·52 mg min-1 kg-1 [0·53-2·52]) for tirzepatide versus semaglutide. On meal tolerance testing, tirzepatide significantly reduced glucose excursions (lower insulin and glucagon concentrations) compared with placebo, with effects on these variables being greater than with semaglutide. The safety profiles of tirzepatide and semaglutide were similar, with gastrointestinal adverse events being the most common (11 [24%], 13 [30%], and seven [25%] with nausea; nine [20%], 13 [30%], and six [21%] with diarrhoea; and three [7%], five [11%], and one [4%] with vomiting, for tirzepatide, semaglutide, and placebo, respectively). There were no deaths. Interpretation: The glycaemic efficacy of GIP/GLP-1 receptor agonist tirzepatide in type 2 diabetes results from concurrent improvements in key components of diabetes pathophysiology, namely β-cell function, insulin sensitivity, and glucagon secretion. These effects were large and help to explain the remarkable glucose-lowering ability of tirzepatide seen in phase 3 studies. Funding: Eli Lilly.

The lancet. Diabetes & endocrinology · randomised controlled trial · 202 citationsread the source →

A double-blind, multicenter, parallel-group study of paroxetine, desipramine, or placebo in breast cancer patients (stages I, II, III, and IV) with major depression.

Objective: This study compared the efficacy and safety of paroxetine and desipramine with those of placebo in the treatment of depressive disorders in adult women with breast cancer, stages I-IV. Method: In a double-blind, placebo-controlled study, 35 female outpatients with breast cancer and DSM-III-R major depression or adjustment disorder with depressed mood were randomly assigned to treatment with paroxetine (N=13), desipramine (N=11), or placebo (N=11) for 6 weeks. Primary efficacy was assessed by change from baseline in score on the 21-item Hamilton Rating Scale for Depression (HAM-D), and the secondary outcome measure was change from baseline in the Clinical Global Impressions-Severity of Illness scale (CGI-S) score. Results: Mean changes in the total HAM-D and CGI-S scores from baseline to 6-week endpoint for the paroxetine and desipramine groups were not significantly different than those for the placebo-treated group. An unusually high rate of response (defined as >or=50% improvement in the HAM-D score) in the placebo group was observed (55% [N=6]); adverse events precipitated patient discontinuation in the active treatment groups (9% [N=1] for desipramine, 15% [N=2] for paroxetine) similar to that in the placebo-treated patients (18% [N=2]). Improvement on symptom dimensions within the HAM-D and Hamilton Rating Scale for Anxiety (depressive, anxiety, cognitive, neurovegetative, or somatic) was also similar between groups. Conclusion: The small number of women in this study most likely contributed to the lack of observed differences in efficacy observed during the 6 weeks of treatment. Randomized, placebo-controlled trials of adequate power seeking to determine efficacy of antidepressants in the United States for the treatment of women with breast cancer and comorbid depression remain of paramount importance.

The Journal of clinical psychiatry · randomised controlled trial · 57 citationsread the source →

Hospital treatment of patients with ischemic stroke or transient ischemic attack using the "Get With The Guidelines" program.

Background: Adherence to evidence-based interventions for hospitalized patients who have experienced a stroke is suboptimal. We examined the association of process improvement and Internet-based data collection and decision support with stroke care. Methods: A 1-year intervention study to assess performance measure adherence in hospitals using the "Get With The Guidelines-Stroke" program. The program included 18 410 patients with ischemic stroke or transient ischemic attack admitted to 99 volunteer community and teaching hospitals. Data from eligible patients in the preintervention baseline period were compared with data from 4 subsequent quarters for 12 acute care or secondary prevention measures and an all-or-none measure of care based on 7 prespecified measures. Results: Significant improvements from baseline to the fourth quarter were seen in 11 of 13 measures: use of thrombolytic medications for patients with ischemic stroke presenting within 2 hours of onset, 23.5% vs 40.8% (P < .001); early use of antithrombotic medications, 88.2% vs 95.2% (P < .001); antithrombotic medications prescribed at discharge, 91.0% vs 97.9% (P < .001); anticoagulation agents for atrial fibrillation, 81.4% vs 96.5% (P < .001); smoking cessation counseling, 38.3% vs 54.5% (P < .001); lipid treatment for low-density lipoprotein levels 100 mg/dL or greater, 58.7% vs 77.0% (P < .001); diabetes mellitus treatment, 48.5% vs 83.5% (P = .001); and weight reduction counseling 32.5% vs 43.4% (P < .001). The all-or-none measure increased from 50.2% to 58.0% (P < .001). Complications from thrombolytic medications and prophylaxis for deep venous thrombosis did not change. Conclusion: Statistically and clinically significant improvement in 11 of 13 quality improvement measures for the treatment of patients hospitalized for cerebrovascular disease was seen in hospitals participating in the Get With The Guidelines program.

Archives of internal medicine · cohort or longitudinal · 158 citationsread the source →

Effects of non-pharmacological interventions on psychological outcomes among older people with frailty: A systematic review and meta-analysis.

Background: Older people with frailty are more likely to experience negative psychological well-being, depressive symptoms, anxiety, and stress. Deterioration of psychological outcomes, in turn, further aggravates the frailty status among this vulnerable population. Considering the undesirable effects of polypharmacy on older people, the use of non-pharmacological intervention has attracted increasing attention. However, the effects of non-pharmacological interventions on psychological outcomes are not clear. Aims: This review aims to systematically identify and synthesise evidence to examine the effectiveness of non-pharmacological interventions on psychological outcomes among older people with frailty. Methods: Eight electronic databases, including PubMed, MEDLINE, EMBASE, CINAHL, APA PsycInfo, Cochrane Library, CNKI and WANFANG were searched from inception to 14 November 2022. Randomised controlled trials and clinical controlled trials of non-pharmacological interventions on psychological outcomes in older people with frailty were included. The quality of the included studies was assessed using The Cochrane Risk of Bias Tool v2. Meta-analysis was performed using the RevMan5.3. The certainty of the evidence was evaluated by GRADE approach. Results: A total of 4726 articles were initially identified and screened for title and abstract. Eventually, 13 articles from 11 studies were included in this review. The results of the overall risk of bias indicated that four studies had low risk; five studies had some concerns, and two studies had high risk. Four types of intervention were identified, including physical exercise (n = 3), complementary and alternative medicine (music therapy = 1, acupressure = 1), case management (n = 5), and advance care planning (n = 1). The pooled analysis showed that group-based physical exercise had significant beneficial effects on depressive symptoms (SMD: -0.46, 95% CI: -0.81 to -0.10, p = .01; low certainty). There is no difference between the effects of case management and usual care on depressive symptoms (SMD: 0.02, 95% CI: -0.14 to 0.19, p = .79; high certainty). Narrative synthesis of evidence suggested the effects of complementary and alternative medicine on improving depressive symptoms and general mental status. Conclusions: Psychological outcomes in older people with frailty are understudied. Group-based physical exercise could be a strategy to reduce depressive symptoms among older people with frailty. There is limited evidence showing the effects of complementary and alternative medicine on improving psychological outcomes. More rigorous trials are needed to examine the effects of non-pharmacological interventions on psychological outcomes among older people with frailty. Registration: (PROSPERO): CRD42022303370.

International journal of nursing studies · meta-analysis · 19 citationsread the source →

The Effectiveness of Social Robots for Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Studies.

Background and objectives: Social robots may promote the health of older adults by increasing their perceived emotional support and social interaction. This review aims to summarize the effectiveness of social robots on outcomes (psychological, physiological, quality of life, or medications) of older adults from randomized controlled trials (RCTs). Research design and methods: A mixed-method systematic review of RCTs meeting the study inclusion criteria was undertaken. Eight databases were electronically searched up to September 2017. Participants' characteristics, intervention features, and outcome data were retrieved. The mean difference and standardized mean difference with 95% confidence intervals (CI) were synthesized to pool the effect size. Results: A total of 13 articles from 11 RCTs were identified from 2,204 articles, of which 9 studies were included in the meta-analysis. Risk of bias was relatively high in allocation concealment and blinding. Social robots appeared to have positive impacts on agitation, anxiety, and quality of life for older adults but no statistical significance was found in the meta-analysis. However, results from a narrative review indicated that social robot interactions could improve engagement, interaction, and stress indicators, as well as reduce loneliness and the use of medications for older adults. Discussion and implications: Social robots appear to have the potential to improve the well-being of older adults, but conclusions are limited due to the lack of high-quality studies. More RCTs are recommended with larger sample sizes and rigorous study designs.

The Gerontologist · meta-analysis · 212 citationsread the source →

Aerobic exercise for adult patients with major depressive disorder in mental health services: A systematic review and meta-analysis.

Although exercise is associated with depression relief, the effects of aerobic exercise (AE) interventions on clinically depressed adult patients have not been clearly supported. The purpose of this meta-analysis was to examine the antidepressant effects of AE versus nonexercise comparators exclusively for depressed adults (18-65 years) recruited through mental health services with a referral or clinical diagnosis of major depression. Eleven e-databases and bibliographies of 19 systematic reviews were searched for relevant randomized controlled clinical trials. A random effects meta-analysis (Hedges' g criterion) was employed for pooling postintervention scores of depression. Heterogeneity and publication bias were examined. Studies were coded considering characteristics of participants and interventions, outcomes and comparisons made, and study design; accordingly, sensitivity and subgroup analyses were calculated. Across 11 eligible trials (13 comparisons) involving 455 patients, AE was delivered on average for 45 min, at moderate intensity, three times/week, for 9.2 weeks and showed a significantly large overall antidepressant effect (g = -0.79, 95% confidence interval = -1.01, -0.57, P < 0.00) with low and nonstatistically significant heterogeneity (I2 = 21%). No publication bias was found. Sensitivity analyses revealed large or moderate to large antidepressant effects for AE (I2 ≤ 30%) among trials with lower risk of bias, trials with short-term interventions (up to 4 weeks), and trials involving individual preferences for exercise. Subgroup analyses revealed comparable effects for AE across various settings and delivery formats, and in both outpatients and inpatients regardless symptom severity. Notwithstanding the small number of trials reviewed, AE emerged as an effective antidepressant intervention.

Depression and anxiety · meta-analysis · 224 citationsread the source →

Nicotine receptor partial agonists for smoking cessation.

Background: Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting as an agonist) and reducing smoking satisfaction (acting as an antagonist). Objectives: To review the efficacy of nicotine receptor partial agonists, including varenicline and cytisine, for smoking cessation. Search methods: We searched the Cochrane Tobacco Addiction Group's specialised register for trials, using the terms ('cytisine' or 'Tabex' or 'dianicline' or 'varenicline' or 'nicotine receptor partial agonist') in the title or abstract, or as keywords. The register is compiled from searches of MEDLINE, EMBASE, and PsycINFO using MeSH terms and free text to identify controlled trials of interventions for smoking cessation and prevention. We contacted authors of trial reports for additional information where necessary. The latest update of the specialised register was in May 2015, although we have included a few key trials published after this date. We also searched online clinical trials registers. Selection criteria: We included randomised controlled trials which compared the treatment drug with placebo. We also included comparisons with bupropion and nicotine patches where available. We excluded trials which did not report a minimum follow-up period of six months from start of treatment. Data collection and analysis: We extracted data on the type of participants, the dose and duration of treatment, the outcome measures, the randomisation procedure, concealment of allocation, and completeness of follow-up. The main outcome measured was abstinence from smoking at longest follow-up. We used the most rigorous definition of abstinence, and preferred biochemically validated rates where they were reported. Where appropriate we pooled risk ratios (RRs), using the Mantel-Haenszel fixed-effect model. Main results: Two trials of cytisine (937 people) found that more participants taking cytisine stopped smoking compared with placebo at longest follow-up, with a pooled risk ratio (RR) of 3.98 (95% confidence interval (CI) 2.01 to 7.87; low-quality evidence). One recent trial comparing cytisine with NRT in 1310 people found a benefit for cytisine at six months (RR 1.43, 95% CI 1.13 to 1.80).One trial of dianicline (602 people) failed to find evidence that it was effective (RR 1.20, 95% CI 0.82 to 1.75). This drug is no longer in development. We identified 39 trials that tested varenicline, 27 of which contributed to the primary analysis (varenicline versus placebo). Five of these trials also included a bupropion treatment arm. Eight trials compared varenicline with nicotine replacement therapy (NRT). Nine studies tested variations in varenicline dosage, and 13 tested usage in disease-specific subgroups of patients. The included studies covered 25,290 participants, 11,801 of whom used varenicline. The pooled RR for continuous or sustained abstinence at six months or longer for varenicline at standard dosage versus placebo was 2.24 (95% CI 2.06 to 2.43; 27 trials, 12,625 people; high-quality evidence). Varenicline at lower or variable doses was also shown to be effective, with an RR of 2.08 (95% CI 1.56 to 2.78; 4 trials, 1266 people). The pooled RR for varenicline versus bupropion at six months was 1.39 (95% CI 1.25 to 1.54; 5 trials, 5877 people; high-quality evidence). The RR for varenicline versus NRT for abstinence at 24 weeks was 1.25 (95% CI 1.14 to 1.37; 8 trials, 6264 people; moderate-quality evidence). Four trials which tested the use of varenicline beyond the 12-week standard regimen found the drug to be well-tolerated during long-term use. The number needed to treat with varenicline for an additional beneficial outcome, based on the weighted mean control rate, is 11 (95% CI 9 to 13). The most commonly reported adverse effect of varenicline was nausea, which was mostly at mild to moderate levels and usually subsided over time. Our analysis of reported serious adverse events occurring during or after active treatment suggests there may be a 25% increase in the chance of SAEs among people using varenicline (RR 1.25; 95% CI 1.04 to 1.49; 29 trials, 15,370 people; high-quality evidence). These events include comorbidities such as infections, cancers and injuries, and most were considered by the trialists to be unrelated to the treatments. There is also evidence of higher losses to follow-up in the control groups compared with the intervention groups, leading to a likely underascertainment of the true rate of SAEs among the controls. Early concerns about a possible association between varenicline and depressed mood, agitation, and suicidal behaviour or ideation led to the addition of a boxed warning to the labelling in 2008. However, subsequent observational cohort studies and meta-analyses have not confirmed these fears, and the findings of the EAGLES trial do not support a causal link between varenicline and neuropsychiatric disorders, including suicidal ideation and suicidal behaviour. The evidence is not conclusive, however, in people with past or current psychiatric disorders. Concerns have also been raised that varenicline may slightly increase cardiovascular events in people already at increased risk of those illnesses. Current evidence neither supports nor refutes such an association, but we await the findings of the CATS trial, which should establish whether or not this is a valid concern. Authors' conclusions: Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and three-fold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion or with NRT. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The most frequently recorded adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Early reports of possible links to suicidal ideation and behaviour have not been confirmed by current research. Future trials of cytisine may test extended regimens and more intensive behavioural support.

The Cochrane database of systematic reviews · meta-analysis · 234 citationsread the source →

Systematic review of measurement tools to assess surgeons' intraoperative cognitive workload.

Background: Surgeons in the operating theatre deal constantly with high-demand tasks that require simultaneous processing of a large amount of information. In certain situations, high cognitive load occurs, which may impact negatively on a surgeon's performance. This systematic review aims to provide a comprehensive understanding of the different methods used to assess surgeons' cognitive load, and a critique of the reliability and validity of current assessment metrics. Methods: A search strategy encompassing MEDLINE, Embase, Web of Science, PsycINFO, ACM Digital Library, IEEE Xplore, PROSPERO and the Cochrane database was developed to identify peer-reviewed articles published from inception to November 2016. Quality was assessed by using the Medical Education Research Study Quality Instrument (MERSQI). A summary table was created to describe study design, setting, specialty, participants, cognitive load measures and MERSQI score. Results: Of 391 articles retrieved, 84 met the inclusion criteria, totalling 2053 unique participants. Most studies were carried out in a simulated setting (59 studies, 70 per cent). Sixty studies (71 per cent) used self-reporting methods, of which the NASA Task Load Index (NASA-TLX) was the most commonly applied tool (44 studies, 52 per cent). Heart rate variability analysis was the most used real-time method (11 studies, 13 per cent). Conclusion: Self-report instruments are valuable when the aim is to assess the overall cognitive load in different surgical procedures and assess learning curves within competence-based surgical education. When the aim is to assess cognitive load related to specific operative stages, real-time tools should be used, as they allow capture of cognitive load fluctuation. A combination of both subjective and objective methods might provide optimal measurement of surgeons' cognition.

The British journal of surgery · systematic review · 154 citationsread the source →

Utility of models to predict 28-day or 30-day unplanned hospital readmissions: an updated systematic review.

Objective: To update previous systematic review of predictive models for 28-day or 30-day unplanned hospital readmissions. Design: Systematic review. Setting/data source: CINAHL, Embase, MEDLINE from 2011 to 2015. Participants: All studies of 28-day and 30-day readmission predictive model. Outcome measures: Characteristics of the included studies, performance of the identified predictive models and key predictive variables included in the models. Results: Of 7310 records, a total of 60 studies with 73 unique predictive models met the inclusion criteria. The utilisation outcome of the models included all-cause readmissions, cardiovascular disease including pneumonia, medical conditions, surgical conditions and mental health condition-related readmissions. Overall, a wide-range C-statistic was reported in 56/60 studies (0.21-0.88). 11 of 13 predictive models for medical condition-related readmissions were found to have consistent moderate discrimination ability (C-statistic ≥0.7). Only two models were designed for the potentially preventable/avoidable readmissions and had C-statistic >0.8. The variables 'comorbidities', 'length of stay' and 'previous admissions' were frequently cited across 73 models. The variables 'laboratory tests' and 'medication' had more weight in the models for cardiovascular disease and medical condition-related readmissions. Conclusions: The predictive models which focused on general medical condition-related unplanned hospital readmissions reported moderate discriminative ability. Two models for potentially preventable/avoidable readmissions showed high discriminative ability. This updated systematic review, however, found inconsistent performance across the included unique 73 risk predictive models. It is critical to define clearly the utilisation outcomes and the type of accessible data source before the selection of the predictive model. Rigorous validation of the predictive models with moderate-to-high discriminative ability is essential, especially for the two models for the potentially preventable/avoidable readmissions. Given the limited available evidence, the development of a predictive model specifically for paediatric 28-day all-cause, unplanned hospital readmissions is a high priority.

BMJ open · systematic review · 180 citationsread the source →

Psychotherapy for depression in older veterans via telemedicine: a randomised, open-label, non-inferiority trial.

Background: Many older adults with major depression, particularly veterans, do not have access to evidence-based psychotherapy. Telemedicine could increase access to best-practice care for older adults facing barriers of mobility, stigma, and geographical isolation. We aimed to establish non-inferiority of behavioural activation therapy for major depression delivered via telemedicine to same-room care in largely male, older adult veterans. Methods: In this randomised, controlled, open-label, non-inferiority trial, we recruited veterans (aged ≥58 years) meeting DSM-IV criteria for major depressive disorder from the Ralph H Johnson Veterans Affairs Medical Center and four associated community outpatient-based clinics in the USA. We excluded actively psychotic or demented people, those with both suicidal ideation and clear intent, and those with substance dependence. The study coordinator randomly assigned participants (1:1; block size 2-6; stratified by race; computer-generated randomisation sequence by RGK) to eight sessions of behavioural activation for depression either via telemedicine or in the same room. The primary outcome was treatment response according to the Geriatric Depression Scale (GDS) and Beck Depression Inventory (BDI; defined as a 50% reduction in symptoms from baseline at 12 months), and Structured Clinical Interview for DSM-IV, clinician version (defined as no longer being diagnosed with major depressive disorder at 12 months follow-up), in the per-protocol population (those who completed at least four treatment sessions and for whom all outcome measurements were done). Those assessing outcomes were masked. The non-inferiority margin was 15%. This trial is registered with ClinicalTrials.gov, number NCT00324701. Findings: Between April 1, 2007, and July 31, 2011, we screened 780 patients, and the study coordinator randomly assigned participants to either telemedicine (120 [50%]) or same-room treatment (121 [50%]). We included 100 (83%) patients in the per-protocol analysis in the telemedicine group and 104 (86%) in the same-room group. Treatment response according to GDS did not differ significantly between the telemedicine (22 [22·45%, 90% CI 15·52-29·38] patients) and same-room (21 [20·39%, 90% CI 13·86-26·92]) groups, with an absolute difference of 2·06% (90% CI -7·46 to 11·58). Response according to BDI also did not differ significantly (telemedicine 19 [24·05%, 90% CI 16·14-31·96] patients; same room 19 [23·17%, 90% CI 15·51-30·83]), with an absolute difference of 0·88% (90% CI -10·13 to 11·89). Response on the Structured Clinical Interview for DSM-IV, clinician version, also did not differ significantly (39 [43·33%, 90% CI 34·74-51·93] patients in the telemedicine group and 46 [48·42%, 90% CI 39·99-56·85] in the same-room group), with a difference of -5·09% (-17·13 to 6·95; p=0·487). Results from the intention-to-treat population were similar. MEM analyses showed that no significant differences existed between treatment trajectories over time for BDI and GDS. The criteria for non-inferiority were met. We did not note any adverse events. Interpretation: Telemedicine-delivered psychotherapy for older adults with major depression is not inferior to same-room treatment. This finding shows that evidence-based psychotherapy can be delivered, without modification, via home-based telemedicine, and that this method can be used to overcome barriers to care associated with distance from and difficulty with attendance at in-person sessions in older adults. Funding: US Department of Veterans Affairs.

The lancet. Psychiatry · randomised controlled trial · 123 citationsread the source →

The Use of Online Posts to Identify Barriers to and Facilitators of HIV Pre-exposure Prophylaxis (PrEP) Among Men Who Have Sex with Men: A Comparison to a Systematic Review of the Peer-Reviewed Literature.

Pre-exposure prophylaxis (PrEP) remains an under-utilized HIV prevention tool among men who have sex with men (MSM). To more comprehensively elucidate barriers and facilitators to PrEP use among US MSM, we conducted a systematic review of peer-reviewed published articles and content analysis of online posts about PrEP. We searched peer-reviewed databases (Medline, Web of Science, Google Scholar) using MESH headings and keywords about PrEP and/or HIV prevention from 2005 to 2015. We included original studies among MSM in the US that reported on barriers, facilitators, or other factors related to PrEP use. We also searched online posts and associated comments (news articles, opinion pieces, blogs and other social media posts) in diverse venues (Facebook, Slate Outward, Huffington Post Gay Voices, Queerty, and My PrEP Experience blog) to identify posts about PrEP. We used content analysis to identify themes and compare potential differences between the peer-reviewed literature and online posts. We identified 25 peer-reviewed articles and 28 online posts meeting inclusion criteria. We identified 48 unique barriers and 46 facilitators to using PrEP. These 94 themes fit into six overarching categories: (1) access (n = 14), (2) attitudes/beliefs (n = 24), (3) attributes of PrEP (n = 13), (4) behaviors (n = 11), (5) sociodemographic characteristics (n = 8), and (6) social network (n = 6). In all categories, analysis of online posts resulted in identification of a greater number of unique themes. Thirty-eight themes were identified in the online posts that were not identified in the peer-reviewed literature. We identified barriers and facilitators to PrEP in online posts that were not identified in a systematic review of the peer-reviewed literature. By incorporating data both from a systematic review of peer-reviewed articles and from online posts, we have identified salient and novel information about barriers to and facilitators of PrEP use. Traditional research approaches may not comprehensively capture current factors important for designing and implementing PrEP related interventions.

AIDS and behavior · systematic review · 68 citationsread the source →

Protective Prevention Effects on the Association of Poverty With Brain Development.

Importance: This study was designed to determine whether a preventive intervention focused on enhancing supportive parenting could ameliorate the association between exposure to poverty and brain development in low socioeconomic status African American individuals from the rural South. Objective: To determine whether participation in an efficacious prevention program designed to enhance supportive parenting for rural African American children will ameliorate the association between living in poverty and reduced hippocampal and amygdalar volumes in adulthood. Design, setting, and participants: In the rural southeastern United States, African American parents and their 11-year-old children were assigned randomly to the Strong African American Families randomized prevention trial or to a control condition. Parents provided data used to calculate income-to-needs ratios when children were aged 11 to 13 years and 16 to 18 years. When the participants were aged 25 years, hippocampal and amygdalar volumes were measured using magnetic resonance imaging. Exposures: Household poverty was measured by income-to-needs ratios. Main outcomes and measures: Young adults' whole hippocampal, dentate gyrus, and CA3 hippocampal subfields as well as amygdalar volumes were assessed using magnetic resonance imaging. Results: Of the 667 participants in the Strong African American Families randomized prevention trial, 119 right-handed African American individuals aged 25 years living in rural areas were recruited. Years lived in poverty across ages 11 to 18 years forecasted diminished left dentate gyrus (simple slope, -14.20; standard error, 5.22; P = .008) and CA3 (simple slope, -6.42; standard error, 2.42; P = .009) hippocampal subfields and left amygdalar (simple slope, -34.62; standard error, 12.74; P = .008) volumes among young adults in the control condition (mean [SD] time, 2.04 [1.88] years) but not among those who participated in the Strong African American Families program (mean [SD] time, 2.61 [1.77] years). Conclusions and relevance: In this study, we described how participation in a randomized clinical trial designed to enhance supportive parenting ameliorated the association of years lived in poverty with left dentate gyrus and CA3 hippocampal subfields and left amygdalar volumes. These findings are consistent with a possible role for supportive parenting and suggest a strategy for narrowing social disparities.

JAMA pediatrics · randomised controlled trial · 92 citationsread the source →

The Social Epidemiology of Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome

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

Impact of Internet-Based Interventions on Caregiver Mental Health: Systematic Review and Meta-Analysis.

Background: The health of informal caregivers of adults with chronic conditions is increasingly vital since caregivers comprise a large proportion of supportive care to family members living in the community. Due to efficiency and reach, internet-based interventions for informal caregivers have the potential to mitigate the negative mental health outcomes associated with caregiving. Objective: The objective of this systematic review and meta-analysis was to examine the impact of internet-based interventions on caregiver mental health outcomes and the impact of different types of internet-based intervention programs. Methods: MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane, and AgeLine databases were searched for randomized controlled trials or controlled clinical trials published from January 1995 to April 2017 that compared internet-based intervention programs with no or minimal internet-based interventions for caregivers of adults with at least 1 chronic condition. The inclusion criteria were studies that included (1) adult informal caregivers (aged 18 years or older) of adults living in the community with a chronic condition; (2) an internet-based intervention program to deliver education, support, or monitoring to informal caregivers; and (3) outcomes of mental health. Title and abstract and full-text screening were completed in duplicate. Data were extracted by a single reviewer and verified by a second reviewer, and risk of bias assessments were completed accordingly. Where possible, data for mental health outcomes were meta-analyzed. Results: The search yielded 7923 unique citations of which 290 studies were screened at full-text. Of those, 13 studies met the inclusion criteria; 11 were randomized controlled trials, 1 study was a controlled clinical trial, and 1 study comprised both study designs. Beneficial effects of any internet-based intervention program resulted in a mean decrease of 0.48 points (95% CI -0.75 to -0.22) for stress and distress and a mean decrease of 0.40 points (95% CI -0.58 to -0.22) for anxiety among caregivers. For studies that examined internet-based information and education plus professional psychosocial support, the meta-analysis results showed small to medium beneficial effect sizes of the intervention for the mental health outcomes of depression (-0.34; 95% CI -0.63 to -0.05) and anxiety (-0.36; 95% CI -0.66 to -0.07). Some suggestion of a beneficial effect on overall health for the use of information and education plus combined peer and professional support was also shown (1.25; 95% CI 0.24 to 2.25). Overall, many studies were of poor quality and were rated at high risk of bias. Conclusions: The review found evidence for the benefit of internet-based intervention programs on mental health for caregivers of adults living with a chronic condition, particularly for the outcomes of caregiver depression, stress and distress, and anxiety. The types of interventions that predominated as efficacious included information and education with or without professional psychological support, and, to a lesser extent, with combined peer and psychological support. Further high-quality research is needed to inform the effectiveness of interactive, dynamic, and multicomponent internet-based interventions. Trial registration: PROSPERO CRD42017075436; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=75436 (Archived by WebCite at http://www.webcitation.org/709M3tDvn).

Journal of medical Internet research · meta-analysis · 100 citationsread the source →

The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis.

Study question: What is the reported overall prevalence of polycystic ovary syndrome (PCOS) according to the criteria of the National Institutes of Health (NIH), Rotterdam or the Androgen Excess and PCOS Society (AE-PCOS Society)? Summary answer: The reported overall prevalence of PCOS (95% CI) according to diagnostic criteria of the NIH, Rotterdam and the AE-PCOS Society is 6% (5-8%, n = 18 trials), 10% (8-13%, n = 15 trials) and 10% (7-13%, n = 10 trials), respectively. What is already known: PCOS is the most common endocrine disorder among women of reproductive age. Although many studies have investigated the prevalence of PCOS, there are discrepancies in their results, in part due to the use of various definitions of the syndrome and its subphenotypes, differences between study cohorts, ethnicities, and types of recruitment and sampling. Study design, size, duration: A systematic review and meta-analysis were performed on all published studies that have reported the prevalence of PCOS according to at least one subset of diagnostic criteria. Participants/materials, setting, methods: To identify relevant studies based on the PRISMA statement, PubMed and Ovid databases were searched up to September 2015 by two blind investigators using the terms 'PCOS', 'polycystic ovarian disease', 'Stein Leventhal syndrome', 'Androgen Excess Society', 'National Institute of Health', 'Rotterdam', 'ESHRE/ASRM', 'criteria' and 'prevalence'. Articles that represented the prevalence of PCOS according to at least one subset of diagnostic criteria were included. Exclusion criteria were a focus on adolescent subjects, an absence of data on prevalence, inappropriate design or non-English reporting. An appraisal tool to evaluate the methodological quality of the available studies was generated by the authors. Main results and the role of chance: A total of 55 reports remained following screening of the abstracts and text for the subject of the study. Of these, 24 articles were eligible and evaluated for qualitative and quantitative synthesis. Since heterogeneity was observed among studies, a random-effects model was used to estimate the prevalence and its 95% CI. The proportions of PCOS prevalence (95% CI) according to the diagnostic criteria of NIH, Rotterdam and AE-PCOS Society were 6% (5-8%, n = 18 trials), 10% (8-13%, n = 15 trials) and 10% (7-13%, n = 10 trials), respectively. When only unselected population studies were included, the given rates were 6% (5-8%, n = 3 trials), 9% (7-12%, n = 6 trials) and 10% (7-14%, n = 3 trials). The respective proportions for hirsutism, hyperandrogenaemia, polycystic ovaries (PCO) and oligo-anovulation were 13% (8-20%, n = 14 trials), 11% (8-15%, n = 9 trials), 28% (22-35%, n = 12 trials) and 15% (12-18%, n = 19 trials), respectively. Limitations, reasons for caution: The effects of ethnic differences, particularly, on the presence or severity of hirsutism cannot be ruled out in any way. In addition, there was a lack of standardization in defining phenotypes of the syndrome and selection bias was evident in most of the studies regarding recruitment of the cohorts. Wider implications of the findings: Geographical differences in frequencies of the components of the syndrome, such as oligo-anovulation and clinical/biochemical androgen excess, must be taken into account in the development and implementation of regional diagnostic and precision treatment strategies. Further efforts and resources are required to increase standardization of the methods and comparability of the study results on prevalence and phenotypic characterization of PCOS around the globe. Study funding/competing interests: No funding to declare. The authors have no conflicts of interest to declare. Registration number: None.

Human reproduction (Oxford, England) · meta-analysis · 918 citationsread the source →

The Amagugu intervention for disclosure of maternal HIV to uninfected primary school-aged children in South Africa: a randomised controlled trial.

Background: Increasing populations of children who are HIV-exposed but uninfected will face the challenge of disclosure of parental HIV infection status. We aimed to test the efficacy of an intervention to increase maternal HIV-disclosure to primary school-aged HIV-uninfected children. Methods: This randomised controlled trial was done at the Africa Health Research Institute in KwaZulu-Natal, South Africa. Women who had tested HIV positive at least 6 months prior, had initiated HIV treatment or been enrolled in pretreatment HIV care, and had an HIV-uninfected child (aged 6-10 years) were randomly allocated to either the Amagugu intervention or enhanced standard of care, using a computerised algorithm based on simple randomisation and equal probabilities of being assigned to each group. Lay counsellors delivered the Amagugu intervention, which included six home-based counselling sessions of 1-2 h and materials and activities to support HIV disclosure and parent-led health promotion. The enhanced standard of care included one clinic-based counselling session. Outcome measures at 3 months, 6 months, and 9 months post baseline were done by follow-up assessors who were masked to participants' group and counsellor allocation. The primary outcome was maternal HIV disclosure (full [using the word HIV], partial [using the word virus], or none) at 9 months post baseline. We did the analysis in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT01922882). Findings: Between July 1, 2013, and Dec 31, 2014, we randomly assigned 464 participants to the Amagugu intervention (n=235) or enhanced standard of care (n=229). 428 (92%) participants completed the 9 month assessment by Sept 3, 2015. Disclosure at any level was more common in the Amagugu intervention group (n=204 [87%]) than in the enhanced standard-of-care group (n=128 [56%]; adjusted odds ratio 9·88, 95% CI 5·55-17·57; p<0·0001). Full disclosure was also more common in the Amagugu intervention group (n=150 [64%]) than in the enhanced standard-of-care group (n=98 [43%]; 4·13, 2·80-6·11; p<0·0001). Treatment-unrelated adverse effects were reported for 17 participants in the Amagugu intervention group versus six in the enhanced standard-of-care group; adverse effects included domestic violence (five [2%] in the Amagugu intervention group vs one [<1%] in the enhanced standard-of-care group), sexual assault (four [2%] vs one [<1%]), participant illness or death (four [2%] vs four [2%]), and family member illness or death (four [2%] vs none). No treatment-related deaths occurred. Interpretation: The lay-counsellor-driven Amagugu intervention to aid parental disclosure has potential for wide-scale implementation after further effectiveness research and could be adapted to other target populations and other diseases. Further follow-up and effectiveness research is required. Funding: National Institutes of Health.

The lancet. HIV · randomised controlled trial · 19 citationsread the source →

Prevalence of depression in cancer patients: a meta-analysis of diagnostic interviews and self-report instruments.

Objective: We aimed to investigate the prevalence of depression in cancer patients assessed by diagnostic interviews and self-report instruments, and to study differences in prevalence between type of instrument, type of cancer and treatment phase. Methods: A literature search was conducted in four databases to select studies on the prevalence of depression among adult cancer patients during or after treatment. A total of 211 studies met the inclusion criteria. Pooled mean prevalence of depression was calculated using Comprehensive Meta-Analysis. Results: Hospital Anxiety and Depression Scale-depression subscale (HADS-D) ≥ 8, HADS-D ≥11, Center for Epidemiologic Studies ≥ 16, and (semi-)structured diagnostic interviews were used to define depression in 66, 53, 35 and 49 studies, respectively. Respective mean prevalence of depression was 17% (95% CI = 16-19%), 8% (95% CI = 7-9%), 24% (95% CI = 21-26%), and 13% (95% CI = 11-15%) (p < 0.001). Prevalence of depression ranged from 3% in patients with lung cancer to 31% in patients with cancer of the digestive tract, on the basis of diagnostic interviews. Prevalence of depression was highest during treatment 14% (95% CI = 11-17%), measured by diagnostic interviews, and 27% (95% CI = 25-30%), measured by self-report instruments. In the first year after diagnosis, prevalence of depression measured with diagnostic interviews and self-report instruments were 9% (95% CI = 7-11%) and 21% (95% CI = 19-24%), respectively, and they were 8% (95% CI = 5-12%) and 15% (95% CI = 13-17%) ≥ 1 year after diagnosis. Conclusions: Pooled mean prevalence of depression in cancer patients ranged from 8% to 24% and differed by the type of instrument, type of cancer and treatment phase. Future prospective studies should disentangle whether differences in prevalence of depression are caused by differences in the type of instrument, type of cancer or treatment phase. © 2013 The Authors. Psycho-Oncology published by John Wiley & Sons, Ltd.

Psycho-oncology · meta-analysis · 595 citationsread the source →

Screening women for intimate partner violence in healthcare settings: abridged Cochrane systematic review and meta-analysis.

Objective: To examine the effectiveness of screening for intimate partner violence conducted within healthcare settings to determine whether or not screening increases identification and referral to support agencies, improves women's wellbeing, decreases further violence, or causes harm. Design: Systematic review and meta-analysis of trials assessing effectiveness of screening. Study assessment, data abstraction, and quality assessment were conducted independently by two of the authors. Standardised estimations of the risk ratios and 95% confidence intervals were calculated. Data sources: Nine databases searched up to July 2012 (CENTRAL, Medline, Medline(R), Embase, DARE, CINAHL, PsycINFO, Sociological Abstracts, and ASSIA), and five trials registers searched up to 2010. Eligibility criteria for selecting studies: Randomised or quasi-randomised trials of screening programmes for intimate partner violence involving all women aged ≥ 16 attending a healthcare setting. We included only studies in which clinicians in the intervention arm personally conducted the screening, or were informed of the screening result at the time of the consultation, compared with usual care (or no screening). Studies of screening programmes that were followed by structured interventions such as advocacy or therapeutic intervention were excluded. Results: 11 eligible trials (n=13,027) were identified. In six pooled studies (n=3564), screening increased the identification of intimate partner violence (risk ratio 2.33, 95% confidence interval 1.39 to 3.89), particularly in antenatal settings (4.26, 1.76 to 10.31). Based on three studies (n=1400), we detected no evidence that screening increases referrals to domestic violence support services (2.67, 0.99 to 7.20). Only two studies measured women's experience of violence after screening (three to 18 months after screening) and found no reduction in intimate partner violence. One study reported that screening does not cause harm. Conclusions: Though screening is likely to increase identification of intimate partner violence in healthcare settings, rates of identification from screening interventions were low relative to best estimates of prevalence of such violence. It is uncertain whether screening increases effective referral to supportive agencies. Screening does not seem to cause harm in the short term, but harm was measured in only one study. As the primary studies did not detect improved outcomes for women screened for intimate partner violence, there is insufficient evidence for screening in healthcare settings. Studies comparing screening versus case finding, or screening in combination with therapeutic intervention for women's long term wellbeing, are needed to inform the implementation of identification policies in healthcare settings.

BMJ (Clinical research ed.) · meta-analysis · 120 citationsread the source →

Safety and efficacy of a cytomegalovirus glycoprotein B (gB) vaccine in adolescent girls: A randomized clinical trial.

Background: Cytomegalovirus (CMV) is a leading cause of congenital infection and an important target for vaccine development. Methods: CMV seronegative girls between 12 and 17 years of age received CMV glycoprotein B (gB) vaccine with MF59 or saline placebo at 0, 1 and 6 months. Blood and urine were collected throughout the study for evidence of CMV infection based on PCR and/or seroconversion to non-vaccine CMV antigens. Results: 402 CMV seronegative subjects were vaccinated (195 vaccine, 207 placebo). The vaccine was generally well tolerated, although local and systemic adverse events were significantly more common in the vaccine group. The vaccine induced gB antibody in all vaccine recipients with a gB geometric mean titer of 13,400 EU; 95%CI 11,436, 15,700, after 3 doses. Overall, 48 CMV infections were detected (21 vaccine, 27 placebo). In the per protocol population (124 vaccine, 125 placebo) vaccine efficacy was 43%; 95%CI: -36; 76, p=0.20. The most significant difference was after 2 doses, administered as per protocol; vaccine efficacy 45%, 95%CI: -9; 72, p=0.08. Conclusion: The vaccine was safe and immunogenic. Although the efficacy did not reach conventional levels of significance, the results are consistent with a previous study in adult women (Pass et al. N Engl J Med 2009;360:1191) using the same formulation.

Vaccine · randomised controlled trial · 190 citationsread the source →

Bowel health to better health: a minimal contact lifestyle intervention for people at increased risk of colorectal cancer.

Colorectal cancer screening forms part of Scotland's cancer reduction strategy. Screened participants, who had undergone colonoscopy and had adenoma(s) removed, were invited to participate in the bowel health to better health (BHBH) programme. BHBH tested the hypothesis that a minimal contact lifestyle intervention could prove effective in promoting changes in diet and activity. Baseline and follow-up questionnaires on lifestyle and psycho-social measures were undertaken in adults randomised to BHBH or a comparison group (CG). The 3-month intervention comprised personalised lifestyle advice, goal-setting and social support to promote increases in physical activity, fibre, fruit and vegetables. Response rate to BHBH was 51 %. BHBH participants (n 32) increased their intake of fibre (DINE FFQ scores 30 (sd 11)-41 (sd 13)) significantly (P < 0.001) more than the CG (n 30; 31 (sd 8)-30 (sd 11). No significant differences between the groups were detected for changes in fruits, vegetables and moderate activity. At baseline, only one participant from each study arm, met the target recommendations for fibre, fruit and vegetable intakes and physical activity. At follow up a significant number of BHBH participants, 15 (47 %) compared to 4 (13 %) of the CG were achieving all three lifestyle recommendations (chi2 (1, n 62) = 8.196, P = 0.006). If sustained, the positive behaviour change achieved through this intervention has the potential to impact on the progression of chronic disease risk including CVD.

The British journal of nutrition · randomised controlled trial · 25 citationsread the source →

Progressive and interrelated functional and structural evidence of post-onset brain reduction in schizophrenia.

Context: Progressive brain abnormalities in schizophrenia remain controversial. Evidence of interrelated progressive functional impairment would buttress the case for structural progression. Mismatch negativity (MMN) is reduced in chronic but not first-hospitalized schizophrenia and may index progressive structural changes. Objective: To determine whether MMN shows associations with underlying auditory cortex gray matter at first hospitalization and progressive reduction longitudinally. Design: Cross-sectional (first hospitalization) and longitudinal (1.5-year follow-up). Setting: A private psychiatric hospital. Participants: Protocol entrance: MMN and magnetic resonance imaging at first hospitalization in 20 subjects with schizophrenia, 21 subjects with bipolar disorder with psychosis, and 32 control subjects. Longitudinal electrophysiologic testing: MMN in 16 subjects with schizophrenia, 17 subjects with bipolar disorder, and 20 control subjects. Longitudinal electrophysiologic testing and magnetic resonance imaging: MMN and magnetic resonance imaging in 11 subjects with schizophrenia, 13 subjects with bipolar disorder, and 13 control subjects. At each time point, reported samples were group matched for age, handedness, and parental socioeconomic status. Interventions: Electrophysiologic testing and high-resolution structural magnetic resonance imaging. Main outcome measures: Mismatch negativity amplitude and Heschl gyrus and planum temporale gray matter volumes. Results: Initially, groups did not differ in MMN amplitude. Subjects with schizophrenia showed associations between MMN and Heschl gyrus (r=-0.52; P=.02) not present in the other groups. At longitudinal MMN testing, schizophrenia showed MMN reduction (P=.004). Only schizophrenia evinced longitudinal left hemisphere Heschl gyrus reduction (P=.003), highly correlated with MMN reduction (r=0.6; P=.04). Conclusions: At first hospitalization for schizophrenia, MMN indexed left hemisphere Heschl gyrus gray matter volume, consistent with variable progression of pre-hospitalization cortical reduction. Longitudinally, the interrelated progressive reduction of functional and structural measures suggests progressive pathologic processes early in schizophrenia. An active process of progressive cortical reduction presents a potential therapeutic target. Mismatch negativity may be a simple, sensitive, and inexpensive index not only of this progressive pathologic process but also of successful intervention.

Archives of general psychiatry · cohort or longitudinal · 288 citationsread the source →

A preliminary study of luteal phase versus symptom-onset dosing with escitalopram for premenstrual dysphoric disorder.

Objective: This preliminary study compared the efficacy and tolerability of escitalopram administered at symptom onset or throughout the luteal phase in premenstrual dysphoric disorder (PMDD). Method: Twenty-seven women meeting DSM-IV criteria for PMDD were randomly assigned in a double-blind manner to luteal phase (N = 13) or symptom-onset (N = 14) dosing of escitalopram (10-20 mg/day) for 3 consecutive menstrual cycles. Participants were enrolled from November 2002 to July 2003, and data collection was completed in December 2003. Symptoms were assessed using the 17-item Penn Daily Symptom Report (DSR), the Clinical Global Impressions-Improvement scale, the Hamilton Rating Scale for Depression, and the Sheehan Disability Scale. Scores were compared using repeated measures analysis of covariance and t statistics. Results: Luteal phase and symptom-onset groups received escitalopram for a mean of 13.5 and 6.0 days, respectively (mean +/- SD dose = 15.2 +/- 5.1 mg/day at the third treatment cycle). Total premenstrual DSR scores significantly improved from baseline (p = .003), with a 57% decrease in the luteal phase group and a 51% decrease in the symptom-onset group. Clinical improvement (DSR score decrease > or = 50% from baseline) was reported by 11 of 13 patients in the luteal phase group and 9 of 14 patients in the symptom-onset group. Symptom severity differentiated the response in the symptom-onset group, with those having more severe symptoms less likely to respond. Symptom severity did not differentiate treatment response to luteal phase dosing. Escitalopram was well tolerated. Adverse events were mild and transient, with only 2 patients discontinuing due to adverse events related to the medication. Conclusion: Premenstrual dysphoric disorder improved significantly with either luteal phase or symptom-onset dosing of escitalopram. Women with more severe PMDD may respond better to luteal phase dosing than symptom-onset dosing.

The Journal of clinical psychiatry · randomised controlled trial · 38 citationsread the source →

Feasibility of Formal Mindfulness-Based Stress-Resilience Training Among Surgery Interns

Importance: Among surgical trainees, burnout and distress are prevalent, but mindfulness has been shown to decrease the risk of depression, suicidal ideation, burnout, and overwhelming stress. In other high-stress populations, formal mindfulness training has been shown to improve mental health, yet this approach has not been tried in surgery. Objective: To test the feasibility and acceptability of modified Mindfulness-Based Stress Reduction (MBSR) training during surgical residency. Design, Setting, and Participants: A pilot randomized clinical trial of modified MBSR vs an active control was conducted with 21 surgical interns in a residency training program at a tertiary academic medical center, from April 30, 2016, to December 2017. Interventions: Weekly 2-hour, modified MBSR classes and 20 minutes of suggested daily home practice over an 8-week period. Main Outcomes and Measures: Feasibility was assessed along 6 domains (demand, implementation, practicality, acceptability, adaptation, and integration), using focus groups, interviews, surveys, attendance, daily practice time, and subjective self-report of experience. Results: Of the 21 residents included in the analysis, 13 were men (62%). Mean (SD [range]) age of the intervention group was 29.0 (2.4 [24-31]) years, and the mean (SD [range]) age of the control group was 27.4 (2.1 [27-33]) years. Formal stress-resilience training was feasible through cultivation of stakeholder support. Modified MBSR was acceptable as evidenced by no attrition; high attendance (12 of 96 absences [13%] in the intervention group and 11 of 72 absences [15%] in the control group); no significant difference in days per week practiced between groups; similar mean (SD) daily practice time between groups with significant differences only in week 1 (control, 28.15 [12.55] minutes; intervention, 15.47 [4.06] minutes; P = .02), week 2 (control, 23.89 [12.93] minutes; intervention, 12.61 [6.06] minutes; P = .03), and week 4 (control, 26.26 [13.12] minutes; intervention, 15.36 [6.13] minutes; P = .04); course satisfaction (based on interviews and focus group feedback); and posttraining-perceived credibility (control, 18.00 [4.24]; intervention, 20.00 [6.55]; P = .03). Mindfulness skills were integrated into personal and professional settings and the independent practice of mindfulness skills continued over 12 months of follow-up (mean days [SD] per week formal practice, 3 [1.0]). Conclusions and Relevance: Formal MBSR training is feasible and acceptable to surgical interns at a tertiary academic center. Interns found the concepts and skills useful both personally and professionally and participation had no detrimental effect on their surgical training or patient care. Trial Registration: ClinicalTrials.gov identifier: NCT03141190.

JAMA Surgery · randomised controlled trial · 130 citationsread the source →

Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial.

Importance: Although vitamin E and memantine have been shown to have beneficial effects in moderately severe Alzheimer disease (AD), evidence is limited in mild to moderate AD. Objective: To determine if vitamin E (alpha tocopherol), memantine, or both slow progression of mild to moderate AD in patients taking an acetylcholinesterase inhibitor. Design, setting, and participants: Double-blind, placebo-controlled, parallel-group, randomized clinical trial involving 613 patients with mild to moderate AD initiated in August 2007 and concluded in September 2012 at 14 Veterans Affairs medical centers. Interventions: Participants received either 2000 IU/d of alpha tocopherol (n = 152), 20 mg/d of memantine (n = 155), the combination (n = 154), or placebo (n = 152). Main outcomes and measures: Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Inventory score (range, 0-78). Secondary outcomes included cognitive, neuropsychiatric, functional, and caregiver measures. Results: Data from 561 participants were analyzed (alpha tocopherol = 140, memantine = 142, combination = 139, placebo = 140), with 52 excluded because of a lack of any follow-up data. Over the mean (SD) follow-up of 2.27 (1.22) years, ADCS-ADL Inventory scores declined by 3.15 units (95% CI, 0.92 to 5.39; adjusted P = .03) less in the alpha tocopherol group compared with the placebo group. In the memantine group, these scores declined 1.98 units less (95% CI, -0.24 to 4.20; adjusted P = .40) than the placebo group's decline. This change in the alpha tocopherol group translates into a delay in clinical progression of 19% per year compared with placebo or a delay of approximately 6.2 months over the follow-up period. Caregiver time increased least in the alpha tocopherol group. All-cause mortality and safety analyses showed a difference only on the serious adverse event of "infections or infestations," with greater frequencies in the memantine (31 events in 23 participants) and combination groups (44 events in 31 participants) compared with placebo (13 events in 11 participants). Conclusions and relevance: Among patients with mild to moderate AD, 2000 IU/d of alpha tocopherol compared with placebo resulted in slower functional decline. There were no significant differences in the groups receiving memantine alone or memantine plus alpha tocopherol. These findings suggest benefit of alpha tocopherol in mild to moderate AD by slowing functional decline and decreasing caregiver burden. Trial registration: clinicaltrials.gov Identifier: NCT00235716.

JAMA · randomised controlled trial · 380 citationsread the source →

The suitability of caffeinated drinks for children: a systematic review of randomised controlled trials, observational studies and expert panel guidelines.

Background: The increased availability of caffeinated drinks raises questions about the level of caffeine that is appropriate for children, as well as the benefits and risks associated with their consumption. Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, this systematic review evaluates evidence from randomised controlled trials investigating the effects of caffeine on cognition, behaviour, mood and exercise performance in children. Observational studies and expert panel guidelines are also discussed. Results: One hundred and nine studies were found, with 11 randomised controlled trials and 13 observational studies meeting the criteria. High caffeine intakes (e.g. >5 mg kg(-1) body weight day(-1)) were associated with an increased risk of anxiety and withdrawal symptoms. However, smaller amounts were not linked with such effects and may benefit cognitive function and sports performance based on adult studies. The evidence suggests that children and adolescents should limit daily caffeine consumption to 2.5 mg kg(-1) body weight day(-1), equating to one or two cups of tea or one small cup of coffee. Lower contributors of caffeine, such as tea, may be more appropriate for children because they contribute to daily fluid intakes and provide flavonoids. By contrast, caffeinated soft drinks may be less suitable options for children as a result of their acidity, higher caffeine content, presence of added sugar (in some cases) and absence of bioactive compounds. Conclusions: More studies are needed to determine the intakes that represent a risk and whether there may be benefits for alertness and sports performance with moderate intakes of caffeine.

Journal of human nutrition and dietetics : the official journal of the British Dietetic Association · systematic review · 30 citationsread the source →

Effectiveness of peer-based healthy living lesson plans on anthropometric measures and physical activity in elementary school students: a cluster randomized trial.

Importance: Schools are considered an attractive setting to promote healthy living behaviors in children, but previous school-based interventions aimed at preventing weight gain in children have yielded mixed results. Novel school-based approaches are needed to modify healthy living behaviors and attenuate weight gain in children. Objective: To assess the effectiveness of a peer-led healthy living program called Healthy Buddies on weight gain and its determinants when disseminated at the provincial level to elementary school students. Design, setting, and participants: Cluster-randomized effectiveness trial performed during the 2009-2010 school year. Baseline and follow-up measurements were made in October 2009 and May 2010, respectively. The study was performed in 19 elementary schools in Manitoba, Canada, and included 647 elementary school students aged 6 to 12 years (48% girls). Intervention: Schools were randomized to receive regular curriculum or Healthy Buddies lesson plans. Lesson plans were delivered by older (9- to 12-year-old) elementary school students to the younger (6- to 8-year-old) peers and targeted 3 components of health: physical activity, healthy eating, and self-esteem and body image. Main outcomes and measures: The primary outcome measures were the change in waist circumference and body mass index z score. Secondary outcomes included physical activity (steps per day), cardiorespiratory fitness, self-efficacy, healthy living knowledge, and self-reported dietary intake. Results: At baseline, 36% of children were overweight or obese and 11% achieved the recommended 13,500 steps per day. Intention-to-treat analyses showed that waist circumference declined significantly in the intervention group relative to controls: -1.42 cm (-2.68 to -0.17; P = .03). Reductions in waist circumference were particularly significant for children who were younger, overweight or obese, or attending First Nations schools. No difference in body mass index z score was observed between groups. Self-efficacy, healthy living knowledge, and dietary intake significantly improved in younger peers who received the intervention compared with students from control schools. No differences were observed in daily step counts or cardiorespiratory fitness between the groups. Conclusions and relevance: The implementation of Healthy Buddies lesson plans delivered by older peers within an elementary school setting is an effective method for attenuating increases in central adiposity and improving knowledge of healthy living behaviors among elementary school students. Improvements were achieved with parallel improvements in diet quality, self-efficacy, and knowledge of healthy living. Trial registration: clinicaltrials.gov Identifier: NCT01979978.

JAMA pediatrics · randomised controlled trial · 54 citationsread the source →

Cross-national analysis of the prevalence of prolonged grief disorder.

Background: Prolonged grief disorder (PGD) is now included as a diagnosis in international classification systems. Most research on PGD is based on Western populations, but first data from non-Western countries have recently become available. Little is still known about country-related effects on PGD's prevalence. Objective: Determining possible causes of variations in the prevalence of PGD as defined by DSM-5-TR and ICD-11 within and between countries. Methods: We retrieved data from 24 prevalence studies, the World Bank and the 2022 World Risk Report. Negative binomial regressions were used to explore methodological, loss-related and country context characteristics as predictors of PGD. The average rate of PGD was calculated using random effects models. Results: The included studies comprised 34 samples from 16 countries (20,347 participants). Non-probability sampling and older mean age of the sample as well as lower country vulnerability were associated with higher PGD rates. The average PGD prevalence was 13 % (95 % CI [11, 22]), varying from 5 % (95 % CI [3, 11]) in probability to 16 % (95 % CI [13, 25]) in non-probability samples. Limitations: Samples from Europe and North America were overrepresented. For about half of the countries, data were available from only one sample. Conclusions: While confirming the importance of studies' methodological quality, the results show that PGD is of public health relevance around the world, but especially common in less vulnerabled countries with better access to daily necessities and healthcare services, highlighting sociocultural impacts on grief processing. Further investigations of cross-national differences are needed.

Journal of affective disorders · 33 citationsread the source →

Lest we forget: comparing retrospective and prospective assessments of adverse childhood experiences in the prediction of adult health.

Background: Adverse childhood experiences (ACEs; e.g. abuse, neglect, and parental loss) have been associated with increased risk for later-life disease and dysfunction using adults' retrospective self-reports of ACEs. Research should test whether associations between ACEs and health outcomes are the same for prospective and retrospective ACE measures. Methods: We estimated agreement between ACEs prospectively recorded throughout childhood (by Study staff at Study member ages 3, 5, 7, 9, 11, 13, and 15) and retrospectively recalled in adulthood (by Study members when they reached age 38), in the population-representative Dunedin cohort (N = 1,037). We related both retrospective and prospective ACE measures to physical, mental, cognitive, and social health at midlife measured through both objective (e.g. biomarkers and neuropsychological tests) and subjective (e.g. self-reported) means. Results: Dunedin and U.S. Centers for Disease Control ACE distributions were similar. Retrospective and prospective measures of adversity showed moderate agreement (r = .47, p < .001; weighted Kappa = .31, 95% CI: .27-.35). Both associated with all midlife outcomes. As compared to prospective ACEs, retrospective ACEs showed stronger associations with life outcomes that were subjectively assessed, and weaker associations with life outcomes that were objectively assessed. Recalled ACEs and poor subjective outcomes were correlated regardless of whether prospectively recorded ACEs were evident. Individuals who recalled more ACEs than had been prospectively recorded were more neurotic than average, and individuals who recalled fewer ACEs than recorded were more agreeable. Conclusions: Prospective ACE records confirm associations between childhood adversity and negative life outcomes found previously using retrospective ACE reports. However, more agreeable and neurotic dispositions may, respectively, bias retrospective ACE measures toward underestimating the impact of adversity on objectively measured life outcomes and overestimating the impact of adversity on self-reported outcomes. Associations between personality factors and the propensity to recall adversity were extremely modest and warrant further investigation. Risk predictions based on retrospective ACE reports should utilize objective outcome measures. Where objective outcome measurements are difficult to obtain, correction factors may be warranted.

Journal of child psychology and psychiatry, and allied disciplines · cohort or longitudinal · 616 citationsread the source →

Dose-dependent and joint associations between screen time, physical activity, and mental wellbeing in adolescents: an international observational study.

Background: Mental wellbeing in adolescents has declined considerably during past decades, making the identification of modifiable risk factors important. Prolonged screen time and insufficient physical activity appear to operate independently and synergistically to increase the risk of poor mental wellbeing in school-aged children. We aimed to examine the gender-stratified dose-dependent and joint associations of screen time and physical activity with mental wellbeing in adolescents. Methods: We used data from three rounds of Health Behaviour in School-aged Children cross-sectional surveys (2006, 2010, and 2014) from 42 European and North American countries. Survey participants, aged 11 years, 13 years, and 15 years, provided self-reported information by completing an anonymous questionnaire that included items on health indicators and related behaviours. We used the self-reported variables of life satisfaction and psychosomatic complaints as indicators of adolescents' mental wellbeing, combining these with the self-reported discretionary use of screens and engagement in physical activity. We used generalised additive models and multilevel regression modelling to examine the gender-stratified relationships between mental wellbeing and screen time and physical activity. Findings: Our sample included 577 475 adolescents (mean age 13·60 years, SD 1·64), with 296 542 (51·35%) girls and 280 933 (48·64%) boys. The mean reported life satisfaction score (on a scale of 0-10) was 7·70 (95% CI 7·69-7·71) in boys and 7·48 (7·46-7·50) in girls. Psychosomatic complaints were more common among girls (mean 9·26, 95% CI 9·23-9·28) than boys (6·89, 6·87-6·91). Generalised additive model analyses showed slightly non-linear associations of screen time and physical activity with life satisfaction and psychosomatic complaints for girls and boys. Detrimental associations between screen time and mental wellbeing started when screen time exceeded 1 h per day, whereas increases in physical activity levels were beneficially and monotonically associated with wellbeing. Multilevel modelling showed that screen time levels were negatively associated with life satisfaction and positively associated with psychosomatic complaints in a dose-dependent manner. Physical activity levels were positively associated with life satisfaction and negatively associated with psychosomatic complaints in a dose-dependent manner. Joint associations of screen time-physical activity with mental wellbeing showed that, compared with the least active participants with more than 8 h per day of screen time and no physical activity, most of the other screen time-physical activity groups had considerably higher life satisfaction and lower psychosomatic complaints. Interpretation: Higher levels of screen time and lower levels of physical activity were associated with lower life satisfaction and higher psychosomatic complaints among adolescents from high-income countries. Public health strategies to promote adolescents' mental wellbeing should aim to decrease screen time and increase physical activity simultaneously. Funding: None.

The Lancet. Child & adolescent health · cohort or longitudinal · 63 citationsread the source →

Coparenting and parenting pathways from the couple relationship to children's behavior problems.

Although an extensive literature has linked couple conflict with the development of children's externalizing behavior problems, longer term protective effects of positive dimensions of couple relationships on children's externalizing behavior remain understudied, particularly in relation to underlying mechanisms. Supportiveness in the dyadic couple relationship may enhance mothers' and fathers' individual parenting skills and protect against children's behavior problems, but the contribution of coparenting (couples' support for one another's individual parenting) remains unclear. This observational study investigated associations between couple supportiveness in children's infancy and middle childhood externalizing problems, exploring pathways involving coparenting and/or mothers' and fathers' individual parenting using data from the U.K. Millennium Cohort Study (MCS; N = 5,779) and the U.S. Fragile Families and Child Wellbeing Study (FFS; N = 2,069). Couple supportiveness was associated with reduced externalizing problems 8 to 10 years later (standardized betas: MCS = -.13, FFS = -.11, both ps < .001). Much of this effect (60% MCS, 55% FFS) was attributable to coparenting and parenting when children were aged 3 to 5 years. Pathways from couple supportiveness involving negative parenting were stronger than those via positive parenting, pathways via mothers' parenting were stronger than those via fathers' parenting, and there were pathways via coparenting alone (without affecting parenting). Pathways involving coparenting were similar in magnitude (MCS), or larger (FFS), than those involving parenting alone. Consistent findings across different population samples suggest that helping parents to support one another in coparenting and to develop their individual parenting skills may lessen the longer term impact of couple relationship problems during early childhood. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Journal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43) · cohort or longitudinal · 30 citationsread the source →

Impact of the Interaction Between Screen Time and Activity Interests on Adolescent Depression Risk: Construction of a Predictive Model Based on Machine Learning.

Background: Adolescent depression is an increasing public health concern, with excessive screen time elevating depression risk and activity interests providing protection. However, most studies examine these behaviors separately and rely on limited analytical methods. This study used machine learning (ML) to develop a predictive model and evaluate the combined influence of screen time and activity interests on adolescent mental health. Methods: A multi-center survey was conducted among adolescents aged 10-14 years in Chongchuan District, Nantong. Depression-related domains were assessed using the Child and Adolescent Mental Health Screening Questionnaire, integrating seven validated scales. A twostage feature-selection strategy identified 11 key predictors. Three ML models (logistic regression [LR], extreme gradient boosting [XGBoost], and categorical boosting [CatBoost]) were trained with an 80:20 stratified split. Class imbalance was addressed using synthetic minority oversampling technique and class-weighting. Model performance and interpretability were evaluated using receiver operating characteristic (ROC) and calibration curves, partial dependence plots, and shapley additive explanations (SHAP) analyses. Results: A total of 2202 valid questionnaires were analyzed. The distribution of depression severity was as follows: safe 59%, mild 17%, moderate 11%, and severe 13%. The integrated questionnaire demonstrated strong reliability (Cronbach's α = 0.910) and good construct validity (Kaiser-Meyer-Olkin [KMO] = 0.91; root mean square error of approximation [RMSEA] = 0.049; and comparative fit index [CFI] = 0.859). ROC-Youden analysis confirmed expert-defined cutoffs (29, 32, and 35). Feature selection identified 11 key predictors, with activity interest and psychological functioning consistently ranking highest in importance. Across the three ML models, LR exhibited the best generalizability, XGBoost showed overfitting, and CatBoost achieved balanced performance. SHAP and partial dependence analyses revealed nonlinear screen-time effects and dose-dependent protective effects of activity interest, including the moderation of high screen exposure in severe-risk groups. Conclusions: This study suggests that ML models can be used to screen adolescents at risk of depression by capturing the combined influence of screen time and activity interests. The model is intended for screening rather than diagnosis and may support school-based early identification, and further validation in clinical contexts is needed.

Actas espanolas de psiquiatria · cohort or longitudinalread the source →

Nursing home residents' perspectives on their social relationships.

Aims and objectives: To explore nursing home residents' perspectives on their relationships with other residents, family members and staff. Background: The cultivation of social relationships is central to promoting well-being in nursing homes, as these relationships allow residents, family members and staff to be valued as unique persons and empowered as partners in care. Few studies have examined how nursing home residents perceive the relationships in their social networks, both within and beyond the facility. Design: Qualitative secondary analysis. Methods: We analysed individual and group interviews obtained during "stakeholder engagement sessions" with cognitively intact residents (N = 11 sessions; N = 13 participants) from two nursing homes in North Carolina. The interviews were conducted as part of a larger study on person-directed care planning. We integrated thematic and narrative analytic approaches to guide the analysis of interview data, using a three-cycle coding approach. The COREQ checklist was followed. Results: Four broad themes emerged from this analysis: (a) peer relationships foster a sense of belonging, purpose, achievement and significance; (b) residents' relationships with family members support a sense of belonging, continuity and significance; (c) mutual respect and reciprocity between residents and nursing home staff promote a sense of belonging and significance; and (d) organisational factors pose barriers to forging meaningful relationships. Each type of relationship-peer, family and staff-made distinctive contributions residents' psychosocial well-being. Conclusion: Recognising the diverse roles of different actors from residents' social networks raises questions for future research to optimise the distinctive contributions of network members that promote residents' psychosocial well-being. Relevance to clinical practice: This study highlights the need for nursing home staff to understand how residents' social relationships influence residents' psychosocial outcomes. Staff training programmes are needed to support residents' rights and to dispel inaccurate interpretations of regulations that threaten sustained meaningful relationships.

Journal of clinical nursing · cohort or longitudinal · 43 citationsread the source →

The EMPOWER blended digital intervention for relapse prevention in schizophrenia: a feasibility cluster randomised controlled trial in Scotland and Australia.

Background: Early warning signs monitoring by service users with schizophrenia has shown promise in preventing relapse but the quality of evidence is low. We aimed to establish the feasibility of undertaking a definitive randomised controlled trial to determine the effectiveness of a blended digital intervention for relapse prevention in schizophrenia. Methods: This multicentre, feasibility, cluster randomised controlled trial aimed to compare Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery (EMPOWER) with treatment as usual in community mental health services (CMHS) in Glasgow and Melbourne. CMHS were the unit of randomisation, selected on the basis of those that probably had five or more care coordinators willing to participate. Participants were eligible if they were older than 16 years, had a schizophrenia or related diagnosis confirmed via case records, were able to provide informed consent, had contact with CMHS, and had had a relapse within the previous 2 years. Participants were randomised within stratified clusters to EMPOWER or to continue their usual approach to care. EMPOWER blended a smartphone for active monitoring of early warning signs with peer support to promote self-management and clinical triage to promote access to relapse prevention. Main outcomes were feasibility, acceptability, usability, and safety, which was assessed through face-to-face interviews. App usage was assessed via the smartphone and self-report. Primary end point was 12 months. Participants, research assistants and other team members involved in delivering the intervention were not masked to treatment conditions. Assessment of relapse was done by an independent adjudication panel masked to randomisation group. The study is registered at ISRCTN (99559262). Findings: We identified and randomised eight CMHS (six in Glasgow and two in Melbourne) comprising 47 care coordinators. We recruited 86 service users between Jan 19 and Aug 8, 2018; 73 were randomised (42 [58%] to EMPOWER and 31 [42%] to treatment as usual). There were 37 (51%) men and 36 (49%) women. At 12 months, main outcomes were collected for 32 (76%) of service users in the EMPOWER group and 30 (97%) of service users in the treatment as usual group. Of those randomised to EMPOWER, 30 (71%) met our a priori criterion of more than 33% adherence to daily monitoring that assumed feasibility. Median time to discontinuation of these participants was 31·5 weeks (SD 14·5). There were 29 adverse events in the EMPOWER group and 25 adverse events in the treatment as usual group. There were 13 app-related adverse events, affecting 11 people, one of which was serious. Fear of relapse was lower in the EMPOWER group than in the treatment as usual group at 12 months (mean difference -7·53 (95% CI -14·45 to 0·60; Cohen's d -0·53). Interpretation: A trial of digital technology to monitor early warning signs blended with peer support and clinical triage to detect and prevent relapse appears to be feasible, safe, and acceptable. A further main trial is merited. Funding: UK National Institute for Health Research Health Technology Assessment programme and the Australian National Health and Medical Research Council.

The lancet. Psychiatry · randomised controlled trial · 50 citationsread the source →

Health Care Professionals' Responses to Religious or Spiritual Statements by Surrogate Decision Makers During Goals-of-Care Discussions.

Importance: Although many patients and their families view religion or spirituality as an important consideration near the end of life, little is known about the extent to which religious or spiritual considerations arise during goals-of-care conversations in the intensive care unit. Objectives: To determine how frequently surrogate decision makers and health care professionals discuss religious or spiritual considerations during family meetings in the intensive care unit and to characterize how health care professionals respond to such statements by surrogates. Design, setting, and participants: A multicenter prospective cohort study was conducted between October 8, 2009, and October 24, 2012, regarding 249 goals-of-care conversations between 651 surrogate decision makers and 441 health care professionals in 13 intensive care units across the United States. Audio-recorded conversations between surrogate decision makers and health care professionals were analyzed, transcribed, and qualitatively coded. Data analysis took place from March 10, 2012, through May 24, 2014. Exposures: Goals-of-care conferences. Main outcomes and measures: Constant comparative methods to develop a framework for coding religious and spiritual statements were applied to the transcripts. Participants completed demographic questionnaires that included religious affiliation and religiosity. Results: Of 457 surrogate decision makers, 355 (77.6%) endorsed religion or spirituality as fairly or very important in their life. Discussion of religious or spiritual considerations occurred in 40 of 249 conferences (16.1%). Surrogates were the first to raise religious or spiritual considerations in most cases (26 of 40). Surrogates' statements (n=59) fell into the following 5 main categories: references to their religious or spiritual beliefs, including miracles (n=34); religious practices (n=19); religious community (n=8); the notion that the physician is God's instrument to promote healing (n=4); and the interpretation that the end of life is a new beginning for their loved one (n=4). Some statements fell into more than 1 category. In response to surrogates' religious or spiritual statements, health care professionals redirected the conversation to medical considerations (n=15), offered to involve hospital spiritual care providers or the patient's own religious or spiritual community (n=14), expressed empathy (n=13), acknowledged surrogates' statements (n=11), or explained their own religious or spiritual beliefs (n=3). In only 8 conferences did health care professionals attempt to further understand surrogates' beliefs, for example, by asking questions about the patient's religion. Conclusions and relevance: Among a cohort of surrogate decision makers with a relatively high degree of religiosity, discussion of religious or spiritual considerations occurred in fewer than 20% of goals-of-care conferences in intensive care units, and health care professionals rarely explored the patient's or family's religious or spiritual ideas.

JAMA internal medicine · cohort or longitudinal · 94 citationsread the source →

What do childhood anxiety disorders predict?

Background: Few longitudinal studies of child and adolescent psychopathology have examined the links between specific childhood anxiety disorders and adolescent psychiatric disorder. In this paper we test the predictive specificity of separation anxiety disorder (SAD), overanxious disorder (OAD), generalized anxiety disorder (GAD), and social phobia. Methods: Data come from the Great Smoky Mountains Study (GSMS). A representative population sample of children--ages 9, 11, and 13 years at intake--was followed to age 19. Diagnoses of both childhood (before age 13 years) and adolescent psychiatric disorders (age 13 to 19 years) were available from 906 participants. Results: Childhood SAD predicted adolescent SAD, whereas OAD was associated with later OAD, panic attacks, depression and conduct disorder (CD). GAD was related only to CD. Social phobia in childhood was associated with adolescent OAD, social phobia, and attention-deficit/hyperactivity disorder (ADHD). Conclusions: Anxiety disorders in childhood are predictors of a range of psychiatric disorders in adolescence. It appears that children meriting a well-defined diagnosis are missed by the current rules for the diagnosis of GAD. Future studies should examine whether OAD deserves reconsideration as a nosological entity.

Journal of child psychology and psychiatry, and allied disciplines · cohort or longitudinal · 391 citationsread the source →

Prediction of differential adult health burden by conduct problem subtypes in males.

Context: A cardinal feature of the DSM-IV diagnostic criteria for conduct disorder is the distinction between childhood- vs adolescent-onset subtypes. Whether such developmental subtypes exist in the population and have different prognoses should be rigorously tested to inform the DSM-V. Objectives: To evaluate the epidemiological validity of childhood- vs adolescent-onset conduct problems in a prospective birth cohort, and to assess whether life-course-persistent conduct problems are associated with a greater adult health burden. Design, setting, and participants: Our sample includes 526 male study members in the Dunedin Multidisciplinary Health and Development Study, a 1-year birth cohort (April 1, 1972, through March 30, 1973). Developmental trajectories were defined using prospective ratings of conduct problems at 7, 9, 11, 13, 15, 18, 21, and 26 years of age. Main outcome measures: Health burden was assessed as mental and physical health problems at 32 years of age measured via diagnostic interviews and physical examinations. Results: We identified the following 4 developmental subtypes of conduct problems through general growth mixture modeling: (1) childhood-onset/life-course-persistent, (2) adolescent onset, (3) childhood limited, and (4) low. At 32 years of age, study members with the life-course-persistent subtype experienced the worst health burden. To a lesser extent, those with the adolescent-onset subtype also experienced health problems. A childhood-limited subtype not specified by DSM-IV was revealed; its adult health outcomes were within the range of the cohort norm. Conclusions: Results support the epidemiological validity of the DSM-IV conduct disorder distinction based on age of onset but highlight the need to also consider long-term persistence to refine diagnosis. Preventing and treating conduct problems has the potential to reduce the adult health burden.

Archives of general psychiatry · cohort or longitudinal · 242 citationsread the source →

Ethnic diversity and pathways to care for a first episode of psychosis in Ontario.

Objective: To examine ethnic variations in the pathways to care for persons accessing early intervention (EI) services in Ontario. Method: The pathways to care and the duration of untreated psychosis were assessed for first-episode psychosis patients who entered specialized EI services in Ontario. The sample was assigned to the following ethnic classifications: the White (Caucasian), Black (African descent), and Asian (ancestry from the continent) groups, plus all the "other ethnicities" group. Results: There were 200 participants: 78% were male; 61% from the White, 15% Black, 13% Asian, and 11% were from the other ethnicities group. At the first point of contact, more participants used nonmedical contacts (12%), such as clergy and naturopathic healers, than psychologists (8%) or psychiatrists (7%). There were no ethnic differences for duration of untreated psychosis (median 22 weeks) or for initiation of help seeking by family/friends (53%), police (15%), or self (33%). After adjusting for relevant clinical and demographic factors, the Asian and other ethnicities groups were 4 and 3 times (respectively) more likely than the White or Black groups (P = .017) to use emergency room services as the first point of contact in the pathways to care. Participants from the Asian group experienced less involuntary hospitalizations (P = .023) than all the other groups. Yet overall, there were many more similarities than significant differences in the pathways to care. Conclusion: EI services should monitor the pathways to care for young people of diverse ethnic backgrounds to address any disparities in accessing care.

Schizophrenia bulletin · cohort or longitudinal · 74 citationsread the source →

Developmental changes in hypothalamus-pituitary-adrenal activity over the transition to adolescence: normative changes and associations with puberty.

Home baseline and laboratory stressor (Trier Social Stress Test for Children) measures of salivary cortisol were obtained from 82 participants (40 girls) aged 9, 11, 13, and 15 years. Measures of pubertal development, self-reported stress, parent reports of child depressive symptoms and fearful temperament, and cardiac measures of sympathetic and parasympathetic activity were also obtained. Significant increases in the home cortisol baselines were found with age and pubertal development. Cortisol stress reactivity differed by age group with 11-year-olds and 13-year-old boys showing blunted reactivity and 9-year-olds, 13-year-old girls, and 15-year-olds showing significant cortisol reactions. Cortisol reactivity correlated marginally with sexual maturation. Measures of sympathetic activity revealed increased sympathetic modulation with age. Higher sympathetic tone was associated with more fearful temperament, whereas greater cortisol reactivity was associated with more anxious and depressed symptoms for girls. The importance of these findings for the hypothesis that puberty-associated increases in hypothalamic-pituitary-adrenal axis activity heightens the risk of psychopathology is discussed.

Development and psychopathology · 466 citationsread the source →

Telehealth versus face-to-face delivery of cognitive behavioural therapy for insomnia: A systematic review and meta-analysis of randomised controlled trials.

ObjectiveThis systematic review and meta-analysis compared the effectiveness of the delivery of care to patients with insomnia via telehealth to its delivery face-to-face. MethodsWe searched Medline, Embase, and Cochrane CENTRAL from inception to 11 January 2023, and conducted a citation analysis on 13 June 2023. No language restrictions were imposed. We included randomised controlled trials. Where feasible, mean differences were calculated; we used a random effects model. ResultsFour trials (239 patients) were included. There were no significant differences between telehealth and face-to-face for insomnia severity scores shortly post-intervention (MD 1.13, 95% CI -0.29-2.55) or at 3 months (mean difference (MD) 1.79, 95% CI -0.01-3.59). There were no differences in Short Form-36 physical and mental scores, Work and Social Adjustment scores, and sleep quality components. Depression scores did not differ post-intervention or at 3 months (MD 0.42, 95% CI -2.42-3.26). Functioning likewise did not differ post-intervention or at 3 months (standardised mean difference (SMD) 0.15, 95% CI -0.37-0.67, P = 0.58). Treatment satisfaction did not differ (one trial) or favoured the face-to-face group (one trial).ConclusionsTelehealth may be a viable alternative to the face-to-face provision of cognitive behavioural therapy for insomnia to patients with insomnia. However, the volume of the existing evidence is limited, therefore additional trials are needed, evaluating cognitive behavioural therapy for insomnia and other therapies for individuals for whom cognitive behavioural therapy for insomnia is not effective, and conducted with a wider range of populations, providers and settings.

Journal of telemedicine and telecare · meta-analysis · 6 citationsread the source →

Midlife contributors to socioeconomic differences in frailty during later life: a prospective cohort study.

Background: Health inequalities persist into old age. We aimed to investigate risk factors for socioeconomic differences in frailty that could potentially be modified through policy measures. Methods: In this multi-wave longitudinal cohort study (Whitehall II study), we assessed participants' socioeconomic status, behavioural and biomedical risk factors, and disease status at age 45-55 years, and frailty (defined according to the Fried phenotype) at baseline and at one or more of three clinic visits about 18 years later (mean age 69 years [SD 5·9]). We used logistic mixed models to examine the associations between socioeconomic status and risk factors at age 50 years and subsequent prevalence of frailty (adjusted for sex, ethnic origin, and age), with sensitivity analyses and multiple imputation for missing data. Findings: Between Sept 9, 2007, and Dec 8, 2016, 6233 middle-aged adults were measured for frailty. Frailty was present in 562 (3%) of 16 164 person-observations, and varied by socioeconomic status: 145 (2%) person-observations had high socioeconomic status, 241 (4%) had intermediate status, and 176 (7%) had low socioeconomic status, adjusting for sex and age. Risk factors for frailty included cardiovascular disease, depression, smoking, high or abstinent alcohol consumption, low fruit and vegetable consumption, physical inactivity, poor lung function, hypertension, and overweight or obesity. Cardiometabolic markers for future frailty were high ratio of total to high-density lipoprotein cholesterol, and raised interleukin-6 and C-reactive protein concentrations. The five most important factors contributing to the frailty gradient, assessed by percent attenuation of the association between socioeconomic status and frailty, were physical activity (13%), interleukin-6 (13%), body-mass index category (11%), C-reactive protein (11%), and poor lung function (10%). Overall, socioeconomic differences in frailty were reduced by 40% in the maximally-adjusted model compared with the minimally-adjusted model. Interpretation: Behavioural and cardiometabolic risk factors in midlife account for more than a third of socioeconomic differences in frailty. Our findings suggest that interventions targeting physical activity, obesity, smoking, and low-grade inflammation in middle age might reduce socioeconomic differences in later-life frailty. Funding: British Heart Foundation and British Medical Research Council.

The Lancet. Public health · 66 citationsread the source →

Standard gastroenterologist versus multidisciplinary treatment for functional gastrointestinal disorders (MANTRA): an open-label, single-centre, randomised controlled trial.

Background: Functional gastrointestinal disorders are common and costly to the health-care system. Most specialist care is provided by a gastroenterologist, but only a minority of patients have improvement in symptoms. Although they have proven to be effective, psychological, behavioural, and dietary therapies are not provided routinely. We aimed to compare the outcome of gastroenterologist-only standard care with multidisciplinary care. Methods: In an open-label, single-centre, pragmatic trial, consecutive new referrals of eligible patients aged 18-80 years with Rome IV criteria-defined functional gastrointestinal disorders were randomly assigned (1:2) to receive gastroenterologist-only standard care or multidisciplinary clinic care. The multidisciplinary clinic included gastroenterologists, dietitians, gut-focused hypnotherapists, psychiatrists, and behavioural (biofeedback) physiotherapists. Randomisation was stratified by Rome IV disorder and whether referred from gastroenterology or colorectal clinic. Outcomes were assessed at clinic discharge or 9 months after the initial visit. The primary outcome was a score of 4 (slightly better) or 5 (much better) on a 5-point Likert scale assessing global symptom improvement. Modified intention-to-treat analysis included all patients who attended at least one clinic visit and who had answered the primary outcome question. This study is registered with ClinicalTrials.gov, NCT03078634. Findings: Between March 16, 2017, and May 10, 2018, 1632 patients referred to the hospital gastrointestinal clinics were screened, of whom 442 were eligible for a screening telephone call and 188 were randomly assigned to receive either standard care (n=65) or multidisciplinary care (n=123). 144 patients formed the modified intention-to-treat analysis (n=46 in the standard-care group and n=98 in the multidisciplinary-care group), 90 (63%) of whom were women. 61 (62%) of 98 patients in the multidisciplinary-care group patients saw allied clinicians. 26 (57%) patients in the standard-care group and 82 (84%) patients in the multidisciplinary-care group had global symptom improvement (risk ratio 1·50 [95% CI 1·13-1·93]; p=0·00045). 29 (63%) patients in the standard-care group and 81 (83%) patients in the multidisciplinary-care group had adequate relief of symptoms in the past 7 days (p=0·010). Patients in the multidisciplinary-care group were more likely to experience a 50% or higher reduction in all Gastrointestinal Symptom Severity Index symptom clusters than were patients in the standard-care group. Of the patients with irritable bowel syndrome, a 50-point or higher reduction in IBS-SSS occurred in 10 (38%) of 26 patients in the standard care group compared with 39 (66%) of 59 patients in the multidisciplinary-care group (p=0·017). Of the patients with functional dyspepsia, a 50% reduction in the Nepean Dyspepsia Index was noted in three (11%) of 11 patients in the standard-care group and in 13 (46%) of 28 in the multidisciplinary-care group (p=0·47). After treatment, the median HADS scores were higher in the standard-care group than in the multidisciplinary-care group (13 [8-20] vs 10 [6-16]; p=0·096) and the median EQ-5D-5L quality of life visual analogue scale was lower in the standard-care group compared with the multidisciplinary-care group (70 [IQR 50-80] vs 75 [65-85]; p=0·0087). The eight SF-36 scales did not differ between the groups at discharge. After treatment, median Somatic Symptom Scale-8 score was higher in the standard-care group than in the multidisciplinary-care group (10 [IQR 7-7] vs 9 [5-13]; p=0·082). Cost per successful outcome was higher in the standard-care group than the multidisciplinary-care group. Interpretation: Integrated multidisciplinary clinical care appears to be superior to gastroenterologist-only care in relation to symptoms, specific functional disorders, psychological state, quality of life, and cost of care for the treatment of functional gastrointestinal disorders. Consideration should be given to providing multidisciplinary care for patients with a functional gastrointestinal disorder. Funding: None.

The lancet. Gastroenterology & hepatology · randomised controlled trial · 89 citationsread the source →

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

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

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

Grief in women with previous miscarriage or stillbirth: a systematic review of cross-sectional and longitudinal prospective studies.

Background: Women who have had miscarriages or stillbirths are known to have a high risk for enduring grief. However, the course and frequency of enduring grief in this subgroup are not fully understood. Objective: Our aims were to assess the intensity of grief and its course in women with miscarriages or stillbirths and to estimate the frequency of severe grief reactions in this population. Additionally, we compared subgroups with miscarriages versus stillbirths and with single versus recurrent pregnancy loss. Method: A systematic literature search of the databases MEDLINE, psycINFO and PSYNDEX was conducted to consider all studies published between 2000 and 31 March 2022 in English or German on the prevalence and intensity of grief in women who had miscarriages or stillbirths. Studies that used validated assessment methods were included in this systematic review. The PRISMA guidelines were followed. Results: Study characteristics and grief data were extracted independently by two investigators from 13 cross-sectional and eight longitudinal studies from 11 countries (N = 2597). All studies used self-reporting instruments. According to 17 of 21 studies (81%), grief is markedly elevated in women after miscarriages or stillbirths. The studies are very heterogeneous regarding the samples, the length of pregnancies and the time of assessment regarding grief after miscarriages. Most studies document intense grief and frequent severe grief reactions - with a decrease over time - in women who have had miscarriages or stillbirths. Clear conclusions regarding corresponding differences between women with miscarriages and stillbirths or single and recurrent pregnancy losses cannot be drawn. Conclusions: Pronounced grief is frequent in women who had miscarriages or stillbirths. More longitudinal studies are needed to examine the course of grief in this group and to identify those women who develop prolonged grief disorder, depression or other mental-health problems.

European journal of psychotraumatology · systematic review · 31 citationsread the source →

Significant Risk of Graft-versus-Host Disease with Exposure to Checkpoint Inhibitors before and after Allogeneic Transplantation.

Investigators are using checkpoint inhibitors (CPIs) to treat aggressive hematologic malignancies in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and in some patients with relapsed disease after allo-HSCT. CTLA-4 inhibitors and PD-1 inhibitors are 2 main types of CPIs, which work through activation of the immune system. On one hand, CPIs can achieve graft-versus-tumor effect, and on the other hand, there is a risk of graft-versus-host disease (GVHD). After a comprehensive literature review, we included data (n = 283) from 24 studies (11 original manuscripts and 13 case reports or case series) and evaluated the results to assess the safety and efficacy of CPI use in conjunction with allo-HSCT. Among the 283 patients, 107 received CPI before allo-HSCT, and 176 received CPI after allo-HSCT. The most common indication for CPI use was for Hodgkin lymphoma. The CPIs used in various studies included ipilimumab, nivolumab, and pembrolizumab. Among the patients exposed to CPI before allo-HSCT, 56% developed acute GVHD and 29% developed chronic GVHD. Investigators reported 20 deaths, 60% of which were GVHD-related. The overall mortality risk with GVHD is 11%. In this group, investigators noted an objective response rate (ORR) in 68% of patients, with complete remission (CR) in 47%, partial remission (PR) in 21%, and stable disease in 11%. Among the patients who received a CPI after allo-HSCT for disease relapse, 14% developed acute GVHD and 9% developed chronic GVHD. Investigators reported 40 deaths, 28% of which were GVHD-related. The mortality risk with GVHD is approximately 7%. Investigators reported ORR in 54% of patients, with CR in 33%, PR in 21%, and disease stabilization in 5%. After careful evaluation of collective data, we found that CPI use both before and after allo-HSCT can be highly effective, but exposure can lead to a significantly increased risk of GVHD-related morbidity and mortality in this patient population. Despite limited availability of data, there is need for extreme caution while making decisions regarding the use of CPIs. Detailed discussions and prospective well-designed clinical trials are needed to explore this issue further.

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · review · 134 citationsread the source →

Autism Spectrum Disorder: A Review.

Importance: Autism spectrum disorder (ASD), characterized by deficits in social communication and the presence of restricted, repetitive behaviors or interests, is a neurodevelopmental disorder affecting approximately 2.3% children aged 8 years in the US and approximately 2.2% of adults. This review summarizes evidence on the diagnosis and treatment of ASD. Observations: The estimated prevalence of ASD has been increasing in the US, from 1.1% in 2008 to 2.3% in 2018, which is likely associated with changes in diagnostic criteria, improved performance of screening and diagnostic tools, and increased public awareness. No biomarkers specific to the diagnosis of ASD have been identified. Common early signs and symptoms of ASD in a child's first 2 years of life include no response to name when called, no or limited use of gestures in communication, and lack of imaginative play. The criterion standard for the diagnosis of ASD is a comprehensive evaluation with a multidisciplinary team of clinicians and is based on semistructured direct observation of the child's behavior and semistructured caregiver interview focused on the individual's development and behaviors using standardized measures, such as the Autism Diagnostic Observation Schedule-Second Edition and the Autism Diagnostic Interview. These diagnostic measures have sensitivity of 91% and 80% and specificity of 76% and 72%, respectively. Compared with people without ASD, individuals with ASD have higher rates of depression (20% vs 7%), anxiety (11% vs 5%), sleep difficulties (13% vs 5%), and epilepsy (21% with co-occurring intellectual disability vs 0.8%). Intensive behavioral interventions, such as the Early Start Denver Model, are beneficial in children 5 years or younger for improvement in language, play, and social communication (small to medium effect size based on standardized mean difference). Pharmacotherapy is indicated for co-occurring psychiatric conditions, such as emotion dysregulation or attention-deficit/hyperactivity disorder. Risperidone and aripiprazole can improve irritability and aggression (standardized mean difference of 1.1, consistent with a large effect size) compared with placebo. Psychostimulants are effective for attention-deficit/hyperactivity disorder (standardized mean difference of 0.6, consistent with a moderate effect size) compared with placebo. These medications are associated with adverse effects including, most commonly, changes in appetite, weight, and sleep. Conclusions and relevance: ASD affects approximately 2.3% of children aged 8 years and approximately 2.2% of adults in the US. First-line therapy consists of behavioral interventions, while co-occurring psychiatric conditions, such as anxiety or aggression, may be treated with specific behavioral therapy or medication.

JAMA · review · 467 citationsread the source →

Marital quality and health: A meta-analytic review.

This meta-analysis reviewed 126 published empirical articles over the past 50 years describing associations between marital relationship quality and physical health in more than 72,000 individuals. Health outcomes included clinical endpoints (objective assessments of function, disease severity, and mortality; subjective health assessments) and surrogate endpoints (biological markers that substitute for clinical endpoints, such as blood pressure). Biological mediators included cardiovascular reactivity and hypothalamic-pituitary-adrenal axis activity. Greater marital quality was related to better health, with mean effect sizes from r = .07 to .21, including lower risk of mortality (r = .11) and lower cardiovascular reactivity during marital conflict (r = -.13), but not daily cortisol slopes or cortisol reactivity during conflict. The small effect sizes were similar in magnitude to previously found associations between health behaviors (e.g., diet) and health outcomes. Effect sizes for a small subset of clinical outcomes were susceptible to publication bias. In some studies, effect sizes remained significant after accounting for confounds such as age and socioeconomic status. Studies with a higher proportion of women in the sample demonstrated larger effect sizes, but we found little evidence for gender differences in studies that explicitly tested gender moderation, with the exception of surrogate endpoint studies. Our conclusions are limited by small numbers of studies for specific health outcomes, unexplained heterogeneity, and designs that limit causal inferences. These findings highlight the need to explicitly test affective, health behavior, and biological mechanisms in future research, and focus on moderating factors that may alter the relationship between marital quality and health.

Psychological Bulletin · meta-analysis · 1568 citationsread the source →

Cystatin C in prediction of acute kidney injury: a systemic review and meta-analysis.

Background: Cystatin C (CysC) has been proposed as a filtration marker for the early detection of acute kidney injury (AKI); however, a wide range of its predictive accuracy has been reported. Study design: Meta-analysis of diagnostic test studies. Setting & population: Various clinical settings of AKI, including patients after cardiac surgery, pediatric patients, and critically ill patients. Selection criteria: Computerized search of PubMed, Current Contents, CINAHL, and EMBASE from inception until November 15, 2010, was performed to identify potentially relevant articles. Inclusion criteria were studies investigating the diagnostic accuracy of CysC level to predict AKI. There were no language restrictions in the search. Index tests: Increasing or increased serum CysC level or urinary CysC excretion. Reference tests: The outcome was the development of AKI, primarily based on serum creatinine level (definition varied across studies). Results: We analyzed data from 19 studies and 11 countries involving 3,336 patients. Of these studies, 13 could be included in the meta-analysis. Across all settings, the diagnostic OR for serum CysC level to predict AKI was 27.7 (95% CI, 12.8-59.8), with sensitivity and specificity of 0.86 and 0.82, respectively. The area under the receiver operating characteristic curve (AUROC) of serum CysC levelto predict AKI was 0.87 (95% CI, 0.81-0.93). In an analysis excluding studies that did not clearly define the measurement time point, early serum CysC (within 24 hours after renal insult or intensive care unit admission) remained of diagnostic value. For the diagnostic value of urinary CysC excretion, the diagnostic OR was 3.10 (95% CI, 2.00-4.81), with sensitivity and specificity of0.61 and 0.67, respectively. TheAUROC of urinary CysC excretion to predict AKI was 0.67 (95% CI, 0.63-0.71) [corrected]. Limitations: Variation in criteria for definitions of index and reference tests, absence of measured glomerular filtration rate in most studies. Conclusion: Serum CysC appears to be a good biomarker in the prediction of AKI, whereas urinary CysC excretion has only moderate diagnostic value.

American journal of kidney diseases : the official journal of the National Kidney Foundation · meta-analysis · 201 citationsread the source →

Omega‐3 fatty acids in colorectal cancer prevention

Colon cancer, which is the fourth most common cancer in the world, is one of the leading causes of cancer death in both men and women in the United States, Canada, Northern and Western Europe, Australia and New Zealand.1, 2 It is markedly less frequent in Asia, Africa and South America.1, 2 Therefore, it is a major public health problem. Migrant and temporal trend studies suggest that colon cancer is determined largely by environmental exposures, especially nutritional habits.1 Marked international differences in the incidence and mortality of colon cancer and increase of risk in populations migrating from low- to high-risk areas such as from Japan, China and the Philippines to the United States within 1 or 2 generations suggest that environmental factors, specifically dietary habits, rather than the genetic factors play an important role in the etiology of this cancer. This upward trend in incidences of colon cancer among Japanese immigrants in Hawaii and California compared to Japanese in Japan stimulated epidemiologists to investigate the reasons for this increase. Although the relationship between nutrition and cancer is complex and sometimes perplexing to nutritionists and to those who visualize carcinogenesis in terms of a specific carcinogen, it should be recognized that nutritional factors and diet may relate to cancer risk in several ways; first, food additives, contaminants, a particular dietary component, or products formed during food preparation may act as carcinogens, cocarcinogens and/or promoters; second, nutrient deficiencies and excesses may lead to biochemical/molecular alterations that may promote neoplastic processes; third, changes in the intake of selected macronutrients may induce metabolic, biochemical and molecular abnormalities that enhance cancer risk; and fourth, certain dietary constituents act as anticarcinogens or chemopreventives. During the last 3 decades, substantial progress has been made in understanding the relationship between dietary constituents and colon cancer risk. Fish oils are unique because they contain high levels of polyunsaturated omega-3 fatty acids (n-3 PUFAs) that are not present in vegetable oils or in saturated fats. Omega-3 fatty acids that are present in fish oil include docosahexaenoic acid (DHA; C22:6), eicosapentaenoic acid (EPA; C20:5) and docosapentaenoic acid (DPA; C22:5). Vegetable oils including corn oil and safflower oil contain high levels of linoleic acid (LA; C18:2). LA has the terminal double-bond 6 carbon atoms from the terminal (omega) methyl group of fatty acid, whereas DHA has the terminal double-bond 3 carbon atoms from the terminal (omega) methyl group of fatty acid (Fig. 1). Chemical structures of omega-3 and omega-6 fatty acids. Nutritional epidemiologic studies have provided evidence that dietary factors are important determinants of colorectal cancer in different populations worldwide. Cancer statistics in Japan for 2001 published by the Foundation for Promotion of Cancer Research indicate that there is an upward trend in age-adjusted mortality rates for colon cancer from 1955 to 1999.3 According to this report, the death rates due to colon cancer in Japanese men and women in 1955 were 2.9 and 3.0, respectively, whereas they increased to 14.7 and 9.8 in 1999. This upward trend in death rates due to colon cancer is mainly attributable to Westernization of Japanese food habits.3, 4 In addition, the report by the Foundation for Promotion of Cancer Research provided the data on the time trends in food consumption, which show increased dietary intakes of animal fat and meat and decreased consumption of whole grains from 1960 to 1999. For example, animal fat consumption in 1960 was about 25 g/day (per capita), whereas in 1999 it increased to about 58 g/day. Meat intake was increased from 19 to 78 g/day (per capita), whereas grain consumption decreased from 453 to 245 g/day during these years.3 The importance of types of dietary fat differing in fatty acid composition rather than total fat cannot be discounted because several preclinical studies using well-established colon cancer models strongly supported the notion that the colon tumor-promoting effect of dietary fat or lack of such effect depends on its fatty acid composition.5 A recent report by an expert panel assembled by the American Institute for Cancer Research/World Cancer Research Fund came to the scientific consensus that evidence for an association between the intake of saturated fat and/or animal fat and colon cancer risk is very strong.6 Continuing population studies revealed that diets particularly high in total fat, especially animal fat, are generally associated with increased risk of developing colon cancer, whereas high dietary fish oil or fish reduces this risk.7, 8 A recent ecologic study suggests that mortality data for colorectal cancer in 22 European countries, the United States and Canada correlate with the consumption of animal fat.7 That eating a diet rich in n-3 PUFAs may decrease the risk of colorectal cancer has been hypothesized in relation to fish and fish oil.7 Caygill and Hill et al.8 reported an inverse correlation between fish and fish oil consumption and colorectal cancer when expressed as a proportion of total or animal fat. This inverse relationship was significant for both male and female colorectal cancer, whether the intakes were in the current period or 10 years or 23 years before cancer mortality, It is noteworthy that these effects were only observed in countries with a high (> 85 g/caput/day) animal fat intake.8 Also, Mediterranean diet rich in olive oil and fish is associated with a low risk of colorectal cancer.9 On the basis of epidemiologic evidence, it is reasonable to suggest that diets high in saturated fats increase the risk of colorectal cancer, whereas diets high in fish and fish oil rich in n-3 PUFAs reduce the risk. Animal models have contributed significantly to understanding of the carcinogenesis process and to study the multiple environmental factors against the pathogenesis of colon cancer.10 Several studies have utilized these relevant animal models to investigate the modulation of colon carcinogenesis by nutritional and chemopreventive agents. These animal models include induction of colon tumors in rats by administration of aromatic amines such as 3,2′-dimethyl-4-aminobi-phenyl (DMBA); derivatives and analogs of cycacin, such as methylazoxymethanol (MAM), 1,2-dimethyl-hydrazine (DMH) and azoxymethane (AOM) in rats and mice of selected strains; direct-acting carcinogens of the type of alkylureas, such as methylnitrosourea (MNU) or N-methyl-N′-nitro-N-nitrosoguanidine (MNNG); and heterocyclic amines such as 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). The spectrum of epithelial lesions induced in the colon by these agents is similar to various types of neoplastic lesions observed in the colorectum of humans. Azoxymethane (AOM), which is a potent inducer of carcinomas of the large intestine in various strains of male and female rats, has been used extensively by many investigators to induce colon tumors and to study the effects of nutritional factors and chemopreventive agents in colon carcinogenesis.10, 11, 12, 13, 14, 15, 16, 17 Colons of Fischer (F344) rats treated with AOM seem to have light and electron microscopic morphology as well as histochemical properties that are quite similar to that of humans and the biologic behavior of AOM-induced rat colon carcinomas is similar to that of human colon carcinomas.10, 18 Other characteristics of the human disease process reflected in the AOM rat model are the occurrence of both adenomas and adenocarcinomas.18 Also, aberrant crypt foci (ACF), which are recognized as early appearing preneoplastic lesions, develop in experimentally induced colon carcinogenesis in laboratory rodents as well as in the colonic mucosa of patients with colon cancer.19, 20 Recently, β-catenin-accumulated crypts were identified in the colonic mucosa at the early stages of AOM-induced colon carcinogenesis and are considered as early-appearing preneoplastic lesions.21 Therefore, ACF are now regarded as putative preneoplastic lesions for colon cancers and are used as biomarkers to evaluate potential chemopreventive agents against colon carcinogenesis.22 AOM treatment also induces oncogene mutations at codon 12 of K- and H-ras and increases in the expression of the ras family of protooncogenes have been causally associated with colon tumor development.23, 24 Enhanced ras oncogene expression has been observed in a variety of human colon tumors.25 AOM-induced colon tumors also demonstrate enhanced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression similar to human colon tumors.13, 26 Mutations in the tumor suppressor gene, APC, are known to be early events in the colon cancer process in humans and have been identified in patients with familial adenomatous polyposis, who have germline mutation in one of the APC alleles, and in sporadic colorectal cancer.27, 28 Evidence in humans thus implicates the APC suppressor gene as causal in large bowel carcinogenesis. Recent studies indicating the presence of APC mutation in AOM-induced colon tumors in rats strengthens the concept that these models are appropriate for human colon cancer studies.29 It has been increasingly apparent that β-catenin signaling pathway is closely associated with the development of colon cancer.30 Also, frequent mutations in the β-catenin gene are confirmed in AOM-induced colon tumors in rodent models.30 it has been that the expression of β-catenin is with the of colon of of of adenomas and ACF and several molecular between human colon tumors and AOM-induced colon it is that the AOM model and induced colon models to be appropriate colon cancer Recent progress in the of molecular carcinogenesis has identified multiple molecular for the and nutritional modulation of colon cancer. The multiple which a mutation codon of the APC gene from a to a is markedly different from that of patients with familial adenomatous in which adenomas are in the colon and whereas in adenomas are in the intestine and in the mice also develop at an early These are potential of and models for agents for potential chemopreventive properties against colon carcinogenesis. The development of for of colorectal cancer by dietary has been markedly by the of relevant laboratory animal including colon cancer the neoplastic process that in humans. and evidence from preclinical studies have provided evidence that not only the also types of dietary fat differing in fatty acid composition are important factors in effect of this nutrient in colon tumor in laboratory and those of have that diets high in and corn oil in the significantly increased induced colon carcinogenesis in and rats as compared to diets low in these studies in laboratory also demonstrate that male rats diets or corn oil rich in PUFAs were to colon carcinogenesis compared with those diets or corn et that dietary n-3 PUFAs methylazoxymethanol of areas of and colon whereas PUFAs enhance colon in In a recent et reported a effect of dietary fish oil against AOM-induced colon carcinogenesis in male dietary fish oil significantly colon tumors as compared to high corn oil In addition, colon tumor by fish oil diet was associated with levels of in the colon compared with corn oil These studies provided evidence in preclinical models that diets high of saturated fat of animal or PUFAs a colon effect than diets low in such fatty whereas diets high in n-3 PUFAs such effect studies in laboratory have the effects of high dietary corn oil and safflower oil rich in olive oil high in fatty acid acid, oil high in fatty acids such as acid and fish oil during the of AOM-induced colon carcinogenesis in male diets high corn oil or safflower oil a incidence of colon tumors than those diets low in fat diets high in olive oil or fish oil such colon The effects of different types of fat on colon carcinogenesis during suggest that fatty acid composition is one of the factors in colon tumor by a dietary fat and that the of types and of dietary fat is during the of In this it is to that in a 2 of patients with colonic dietary fish oil have in in the colonic progress has been made with to the relationship between dietary fat intake and colon cancer risk in that of the tumor-promoting effects of diets rich in PUFAs and saturated fatty acids and lack of such effects by n-3 it should be recognized that among the of dietary fat, animal fat with its fatty acid is by the most important to about to the Western dietary fat intake in the United States and Canada and Western countries, colon cancer rates are of a of and polyunsaturated A recent in mice that high dietary fat composition of the diet lesions in the colon of In of the of in colon cancer and because of potential properties of n-3 have a study to the effects of diets that contain rich in saturated fatty acids and to with the effects of fish oil during the different stages of colon carcinogenesis in male preneoplastic lesions, were in the diets for 23 and which are putative preneoplastic lesions in the were observed at high in the colonic mucosa of patients with colon and of rats and mice treated with colon ACF and are to be biomarkers of the effects of agents carcinogenesis in the ACF were observed in the of the diet a significantly of compared with those the corn oil or fish oil diet at time The incidence of aberrant foci was also in the diet group than in the or diet that administration of the diet significantly the and of preneoplastic lesions in the whereas the diet the of such Also, dietary significantly increased colon tumor incidence and when compared with the or rats the diet incidence of colonic compared with incidences of and in rats the and Also, the of was significantly in the diet as compared to those the the diet fat in the of fish induced tumors than diet the of total fat from This that both the type and the of fatty acids in the diet play a role in colon carcinogenesis. In evidence from preclinical studies is with the epidemiologic The of dietary n-3 PUFAs including DHA and against colon carcinogenesis has also been in rodent et reported that administration of of DHA a for 4 and 12 significantly AOM-induced ACF in the et also reported that administration of 1 of DHA a for significantly AOM-induced colon tumor specifically in the and colon in male et compared dietary at LA at or LA at against AOM-induced colon carcinogenesis in male The indicate that the rats a significantly colon tumor incidence and than those the LA of tumors that the rats on diet and than those on the LA Also, the of in the colon tumors of LA diet group was than that in the colon tumors of the diet These suggest that its effect the modulation of in colon Several potential have been for colon cancer of types of dietary fat. Several studies indicate that diets high in saturated fatty acids and and PUFAs oil or safflower increase the of colonic including acid and acid, whereas dietary fish oil high in n-3 PUFAs such epidemiologic studies that populations who are on Western diet and at high risk for colon cancer high levels of acids have been to in a similar to induce and a in and act as in colon these suggest that acids that are by types of dietary fat may be important for in relation to colon tumor in by et dietary PUFAs may and n-3 PUFAs may against colon carcinogenesis by and/or levels of AOM-induced were in fish rats as compared to those corn oil rich in et and et have also that fish oil an increase in in the colon compared with corn It is reasonable to that one of the by which n-3 PUFAs against colon carcinogenesis is in by the of and by the of colonic Also, of fish oil or n-3 fatty acid increased and DHA levels in the of at the of fatty It has been that of colon carcinogenesis by DHA is the of a of a large of n-3 PUFAs effects in the colon the of of the are factors that and are studies to indicate that inducible nitric oxide synthase which is at the is in human colon and in induced colon tumors of laboratory animal data also indicate that the of by is to carcinogenesis process and induces lesions, thus in and in the by family of also These data suggest a role for in tumor and in laboratory indicate that acid induces in with specific expression that one of the by which tumor including acids may an increase in expression of pathway that colon It is known that the fatty acid composition of is to in laboratory indicate that levels of dietary fish oil in rats increased the omega-3 fatty DHA and in the colonic at the of omega-6 PUFAs such as linoleic acid and acid, the that the DHA and of fish oil the of by acid and linoleic acid in the Therefore, the types of dietary fat the fatty acid composition of colonic It is well that acid and of its including play an important role in the signaling pathway associated with and gene increase promote and of which are in tumor The by which n-3 PUFAs colon carcinogenesis are in of an important role in colon and who have in the of of rat epithelial have that of lead to the of high intake of saturated fat and omega-6 PUFAs acid from and levels of have been observed in human colon tumors and induced colon tumors in rodent and human colon levels of that are by Northern Recent have a between the potential of APC mutations and by that of the gene reduces the of tumors in mice for an by than evidence a role for from which show a in colon tumors in rodents with Recent studies in laboratory have provided evidence that an diet AOM-induced expression of and from acid in colon tumors of rats, whereas the diet the levels of In this administration of the diet of in the colon significantly levels than the corn oil diet or the diet 28 indicating This suggests that of the modulation of may be important for the of n-3 PUFAs to colon Also, colon tumors of the diet a than was observed in the colon tumors of rats the The of these studies indicating that of in the tumors of the diet in to the diet and the tumor the that of lead to the of In colon the levels of may be to by and induction of and thus tumor A major that to be is which signaling are in of the These not only a between dietary fatty and of colon also molecular for colon cancer by which n-3 PUFAs colon carcinogenesis. The potential and molecular events by n-3 PUFAs against colon carcinogenesis. The of molecular events by n-3 PUFAs include including and specific and factors including that and dietary n-3 PUFAs by with the and of modulation of thus Recent studies from laboratory have that high dietary PUFAs enhance of including that have been or in colon tumor whereas diet n-3 PUFAs to the of these a gene family of that play in signaling events and are in and include several with unique to the from the et reported that chemopreventive of dietary fish oil is associated with the alterations in colonic a that is by PUFAs may the of the which a of It is that several have been to in The a of ras that is to the of in the of of are in the etiology of human colon It is also known that of from to is by a of closely including which is by It that of ras association of and neoplastic of in laboratory have provided data to indicate that high dietary PUFAs increases expression in colonic whereas high dietary n-3 PUFAs to by with and of the modulation of thus Several have against in both and laboratory animal in have the of in and of colon cancer. of is with the development of certain of has also been to induce an effect that with and have that expression of was in colon tumors of rats than in colon Colon tumors from rats the diet high levels of PUFAs very low levels of whereas the tumors from the diet high of n-3 PUFAs not of These correlate with colon tumor incidences by dietary n-3 and It that modulation of a significant role in n-3 colon tumor and studies in laboratory have that DHA of colon cancer in and induces also the effects of DHA on the genetic of human colon cancer at the using in gene expression due to DHA treatment was observed to be in the multiple signaling in the of and of DHA on and induction of were by an increase in the of several of family of and of such as and of several of these and factors the of the chemopreventive of DHA and important n-3 PUFAs present in fish oil and thus colon cancer. Also, of these and factors provided several expressed biologic many of which suggest as molecular for by chemopreventive including nutritional is a major of and mortality in patients with cancer, including colorectal cancer. Several studies have provided evidence for effects of fish oil administration in cancer during Omega-3 fatty acids have been to have effects on in cancer in patients with cancer is to and is associated with a time and of A fish nutritional has the potential to be a and of a fish oil preparation of and and a preparation in patients with 85 The of of the of which in the of of cancer patients and death from attributable to of of in cancer by and this may be one of the for of tumor Also, fish oil at a of during In on the basis of epidemiologic evidence from ecologic and it is reasonable to suggest that diets high in saturated fats increase the risk of colorectal cancer, whereas diets high in n-3 PUFAs not increase its risk. The studies both epidemiologic and evidence for the effects of diets rich in n-3 in the of colorectal cancer. Also, recent demonstrate effects of fish oil administration in cancer and during and studies have provided evidence that colon tumor-promoting effect of dietary fat depends on its fatty acid that the composition of dietary fatty acids is to colon cancer risk than is the total of fat. studies also demonstrate that a diet high in including saturated fats of animal as well as high dietary PUFAs a potential to promote colon than of a diet on of fat n-3 Although the by which diets high in saturated fats as those in Western and PUFAs promote colon carcinogenesis are not the studies thus indicate that increased levels of colonic modulation of the on and the expression of by the types of dietary fat, especially may play a role in colon carcinogenesis. studies are to the role of n-3 PUFAs on the modulation of that are in colon and types of cancer. The of is to decrease the and mortality from colorectal cancer. and those of suggest that nutritional has the potential to be a major of colorectal cancer especially in the are and in n-3 PUFAs be before they are for cancer Although there are data to indicate and n-3 PUFAs should be for of colorectal cancer, levels of dietary n-3 PUFAs should be with the on epidemiologic studies of disease as by several These studies suggest that fish or as as g/day of fish the risk of Although a dietary for n-3 PUFAs not there is a that consumption of of fish in on the epidemiologic studies may also reduce the risk of colorectal cancer. et has that the of PUFAs to n-3 PUFAs may be important for The risk for and several types of cancer among Mediterranean and Western European populations may at in be on the basis of to n-3 of and 10 in on preclinical and epidemiologic studies on and et for a in the intake of linoleic acid and increase in the intake of n-3 PUFAs that a of 2 be for of and that this is in Western countries for of and and This may well be for the of colorectal cancer in the consumption of and is also for those in Western countries to reduce the risk of colorectal cancer. In the of colorectal cancer in omega-3 fatty acids are in and of be It should be recognized that with nutritional and/or diet may not be for of colorectal cancer in patients such as those with and sporadic colon This to colon cancer is of importance as have not been in the high incidence or low of colorectal cancer. by diet as to the with chemopreventive agents that or the development of those which with and progress to and is an for of colon cancer in these high-risk This is important when chemopreventive agents demonstrate significant may effects at It is certain that colon cancer be a significant of and in high-risk by molecular that or the process of carcinogenesis. there is a to in patients with sporadic colon using the n-3 diets in with a chemopreventive to the of events leading to The for preparation of the and studies on n-3 PUFAs in colon cancer are supported by the Cancer Institute and

International Journal of Cancer · review · 65 citationsread the source →

Mindfulness-based mobile applications: literature review and analysis of current features.

Background: Interest in mindfulness has increased exponentially, particularly in the fields of psychology and medicine. The trait or state of mindfulness is significantly related to several indicators of psychological health, and mindfulness-based therapies are effective at preventing and treating many chronic diseases. Interest in mobile applications for health promotion and disease self-management is also growing. Despite the explosion of interest, research on both the design and potential uses of mindfulness-based mobile applications (MBMAs) is scarce. Objective: Our main objective was to study the features and functionalities of current MBMAs and compare them to current evidence-based literature in the health and clinical setting. Methods: We searched online vendor markets, scientific journal databases, and grey literature related to MBMAs. We included mobile applications that featured a mindfulness-based component related to training or daily practice of mindfulness techniques. We excluded opinion-based articles from the literature. Results: The literature search resulted in 11 eligible matches, two of which completely met our selection criteria-a pilot study designed to evaluate the feasibility of a MBMA to train the practice of "walking meditation," and an exploratory study of an application consisting of mood reporting scales and mindfulness-based mobile therapies. The online market search eventually analyzed 50 available MBMAs. Of these, 8% (4/50) did not work, thus we only gathered information about language, downloads, or prices. The most common operating system was Android. Of the analyzed apps, 30% (15/50) have both a free and paid version. MBMAs were devoted to daily meditation practice (27/46, 59%), mindfulness training (6/46, 13%), assessments or tests (5/46, 11%), attention focus (4/46, 9%), and mixed objectives (4/46, 9%). We found 108 different resources, of which the most used were reminders, alarms, or bells (21/108, 19.4%), statistics tools (17/108, 15.7%), audio tracks (15/108, 13.9%), and educational texts (11/108, 10.2%). Daily, weekly, monthly statistics, or reports were provided by 37% (17/46) of the apps. 28% (13/46) of them permitted access to a social network. No information about sensors was available. The analyzed applications seemed not to use any external sensor. English was the only language of 78% (39/50) of the apps, and only 8% (4/50) provided information in Spanish. 20% (9/46) of the apps have interfaces that are difficult to use. No specific apps exist for professionals or, at least, for both profiles (users and professionals). We did not find any evaluations of health outcomes resulting from the use of MBMAs. Conclusions: While a wide selection of MBMAs seem to be available to interested people, this study still shows an almost complete lack of evidence supporting the usefulness of those applications. We found no randomized clinical trials evaluating the impact of these applications on mindfulness training or health indicators, and the potential for mobile mindfulness applications remains largely unexplored.

JMIR mHealth and uHealth · review · 84 citationsread the source →

Workers' health and productivity under occupational heat strain: a systematic review and meta-analysis.

Background: Occupational heat strain (ie, the effect of environmental heat stress on the body) directly threatens workers' ability to live healthy and productive lives. We estimated the effects of occupational heat strain on workers' health and productivity outcomes. Methods: Following PRISMA guidelines for this systematic review and meta-analysis, we searched PubMed and Embase from database inception to Feb 5, 2018, for relevant studies in any labour environment and at any level of occupational heat strain. No restrictions on language, workers' health status, or study design were applied. Occupational heat strain was defined using international health and safety guidelines and standards. We excluded studies that calculated effects using simulations or statistical models instead of actual measurements, and any grey literature. Risk of bias, data extraction, and sensitivity analysis were performed by two independent investigators. Six random-effects meta-analyses estimated the prevalence of occupational heat strain, kidney disease or acute kidney injury, productivity loss, core temperature, change in urine specific gravity, and odds of occupational heat strain occurring during or at the end of a work shift in heat stress conditions. The review protocol is available on PROSPERO, registration number CRD42017083271. Findings: Of 958 reports identified through our systematic search, 111 studies done in 30 countries, including 447 million workers from more than 40 different occupations, were eligible for analysis. Our meta-analyses showed that individuals working a single work shift under heat stress (defined as wet-bulb globe temperature beyond 22·0 or 24·8°C depending on work intensity) were 4·01 times (95% CI 2·45-6·58; nine studies with 11 582 workers) more likely to experience occupational heat strain than an individual working in thermoneutral conditions, while their core temperature was increased by 0·7°C (0·4-1·0; 17 studies with 1090 workers) and their urine specific gravity was increased by 14·5% (0·0031, 0·0014-0·0048; 14 studies with 691 workers). During or at the end of a work shift under heat stress, 35% (31-39; 33 studies with 13 088 workers) of workers experienced occupational heat strain, while 30% (21-39; 11 studies with 8076 workers) reported productivity losses. Finally, 15% (11-19; ten studies with 21 721 workers) of individuals who typically or frequently worked under heat stress (minimum of 6 h per day, 5 days per week, for 2 months of the year) experienced kidney disease or acute kidney injury. Overall, this analysis include a variety of populations, exposures, and occupations to comply with a wider adoption of evidence synthesis, but resulted in large heterogeneity in our meta-analyses. Grading of Recommendations, Assessment, Development and Evaluation analysis revealed moderate confidence for most results and very low confidence in two cases (average core temperature and change in urine specific gravity) due to studies being funded by industry. Interpretation: Occupational heat strain has important health and productivity outcomes and should be recognised as a public health problem. Concerted international action is needed to mitigate its effects in light of climate change and the anticipated rise in heat stress. Funding: EU Horizon 2020 research and innovation programme.

The Lancet. Planetary health · meta-analysis · 253 citationsread the source →

Into the realm of social capital for adolescents: A latent profile analysis.

Background: Recent reports of increasing prevalence of frequent health complaints and mental health problems among adolescents call for directing more attention on determinants of adolescent health. The relationship between health and social capital has gained increased attention since the early 2000's and research at review level confirms the importance of social capital for health outcomes, despite methodological heterogeneity. The aim of this study was to identify distinct profiles of family, school and peer social capital in a nationally representative sample of adolescents and to explore health outcomes in those profiles. Method: Cross-sectional data from the Swedish Health Behaviour of School-aged Children 2013/14 was used for this study. The analytical sample consisted of 7,804 adolescents aged 11-, 13- and 15-years. Items representing sense of belonging and emotional support were assessed in three contexts; family, school and among peers. Latent profile analyses (LPA) were run to determine social capital profiles. Health outcomes included frequent health complaints and life satisfaction, while socioeconomic status and genders were included as predictors. Results: The results show that five distinct profiles best represent the data for 11- and 15-year olds, while a four-profile model was optimal for 13-year olds. Some profiles were recurrent between age groups but unique profiles were also found. Health outcomes were significantly different between profiles depending on levels of social capital in the different contexts. Conclusions: This study provides novel insight into how social capital co-occurs among adolescents within the contexts of family, school and peers and how this translates into differences in health outcomes. The national representativeness of the sample increases the implications of the results and contributes to meaningful insights that help explain the interactions of social capital in multiple contexts, complementing what is previously known about the relationship with adolescent health.

PloS one · 10 citationsread the source →

A systematic review, meta-analysis, and meta-regression of the impact of diurnal intermittent fasting during Ramadan on glucometabolic markers in healthy subjects.

Aim: Studies on the effect of Ramadan diurnal intermittent fasting (RDIF) on glucometabolic markers have yielded conflicting results. We conducted ameta-analysis to estimate the effect size for changes in glucometabolic markers in healthy, non-athletic Muslims during Ramadan, and to assess the effect of variable covariates using meta-regression. Methods: CINAHL, Cochrane, EBSCOhost, EMBASE, Google Scholar, ProQuest Medical, PubMed/MEDLINE, ScienceDirect, Scopus, and Web of Science databases were searched from date of inceptionto January 2020. The glucometabolic markers analyzed were: fasting glucose (FG), insulin, insulin resistance (HOMA-IR), leptin, and adiponectin. Results: We identified seventy-two studies (3134 participants in total) that were conducted in 22 countries between 1982 and 2020. RDIF-induced effect sizes for the glucometabolic markers were: FG (no. of studies K = 61, number of subjects N = 2743, Hedges'g = -0.102, 95% CI: -0.194, -0.01); serum insulin (K = 16, N = 648, Hedges'g = 0.030 95% CI: -0.165, 0.226); HOMA-IR (K = 10, N = 349, Hedges'g = -0.012, 95% CI: -0.274, 0.250); leptin (K = 13, N = 442, Hedges'g = -0.010, 95% CI: -0.243, 0.223); and adiponectin (K = 11, N = 511, Hedges'g = 0.034, 95% CI: -0.227, 0.296). Conclusion: RDIF imposes no adverse metabolic impacts, and might help in improving some glucometabolic markers in healthy subjects.

Diabetes research and clinical practice · meta-analysis · 66 citationsread the source →

Age- and sex-based differences in the moral intuitions of American early adolescents.

This study sought to explore the validity of a latent-factor model of moral intuition development during early adolescence. The 3-Factor Character Foundations Survey (CFS-3) was used to assess the moral intuitions of early adolescents (n = 850, mean = 12.4 years old, SD = 0.96) under a moral foundations theory framework. Confirmatory factor analysis supported the psychometric validity of the three latent factor constructs (autonomy, loyalty and empathy), and partial metric invariance was established to allow for the comparison of latent factor means between four age- and sex-based groups coinciding with averages for pubertal onset. Results support prior findings of greater latent factor means for females in all three factors when compared with males in the 11-12-year-old age group. Additionally, 13-14-year-old females exhibited lower latent factor means in autonomy and loyalty factors when compared with 11-12-year-old females. This resulted in 13-14-year-old females remaining higher in empathy and autonomy but showing no difference in loyalty when compared with 13-14-year-old males. The results are interpreted through the lens of attachment theory, socio-cultural influence and certain limitations of the survey instrument itself. Suggestions for future studies are proposed.

Evolutionary human sciences · 2 citationsread the source →

Alcoholics Anonymous and other 12-step programs for alcohol use disorder.

Background: Alcohol use disorder (AUD) confers a prodigious burden of disease, disability, premature mortality, and high economic costs from lost productivity, accidents, violence, incarceration, and increased healthcare utilization. For over 80 years, Alcoholics Anonymous (AA) has been a widespread AUD recovery organization, with millions of members and treatment free at the point of access, but it is only recently that rigorous research on its effectiveness has been conducted. Objectives: To evaluate whether peer-led AA and professionally-delivered treatments that facilitate AA involvement (Twelve-Step Facilitation (TSF) interventions) achieve important outcomes, specifically: abstinence, reduced drinking intensity, reduced alcohol-related consequences, alcohol addiction severity, and healthcare cost offsets. Search methods: We searched the Cochrane Drugs and Alcohol Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, CINAHL and PsycINFO from inception to 2 August 2019. We searched for ongoing and unpublished studies via ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 15 November 2018. All searches included non-English language literature. We handsearched references of topic-related systematic reviews and bibliographies of included studies. Selection criteria: We included randomized controlled trials (RCTs), quasi-RCTs and non-randomized studies that compared AA or TSF (AA/TSF) with other interventions, such as motivational enhancement therapy (MET) or cognitive behavioral therapy (CBT), TSF treatment variants, or no treatment. We also included healthcare cost offset studies. Participants were non-coerced adults with AUD. Data collection and analysis: We categorized studies by: study design (RCT/quasi-RCT; non-randomized; economic); degree of standardized manualization (all interventions manualized versus some/none); and comparison intervention type (i.e. whether AA/TSF was compared to an intervention with a different theoretical orientation or an AA/TSF intervention that varied in style or intensity). For analyses, we followed Cochrane methodology calculating the standard mean difference (SMD) for continuous variables (e.g. percent days abstinent (PDA)) or the relative risk (risk ratios (RRs)) for dichotomous variables. We conducted random-effects meta-analyses to pool effects wherever possible. Main results: We included 27 studies containing 10,565 participants (21 RCTs/quasi-RCTs, 5 non-randomized, and 1 purely economic study). The average age of participants within studies ranged from 34.2 to 51.0 years. AA/TSF was compared with psychological clinical interventions, such as MET and CBT, and other 12-step program variants. We rated selection bias as being at high risk in 11 of the 27 included studies, unclear in three, and as low risk in 13. We rated risk of attrition bias as high risk in nine studies, unclear in 14, and low in four, due to moderate (> 20%) attrition rates in the study overall (8 studies), or in study treatment group (1 study). Risk of bias due to inadequate researcher blinding was high in one study, unclear in 22, and low in four. Risks of bias arising from the remaining domains were predominantly low or unclear. AA/TSF (manualized) compared to treatments with a different theoretical orientation (e.g. CBT) (randomized/quasi-randomized evidence) RCTs comparing manualized AA/TSF to other clinical interventions (e.g. CBT), showed AA/TSF improves rates of continuous abstinence at 12 months (risk ratio (RR) 1.21, 95% confidence interval (CI) 1.03 to 1.42; 2 studies, 1936 participants; high-certainty evidence). This effect remained consistent at both 24 and 36 months. For percentage days abstinent (PDA), AA/TSF appears to perform as well as other clinical interventions at 12 months (mean difference (MD) 3.03, 95% CI -4.36 to 10.43; 4 studies, 1999 participants; very low-certainty evidence), and better at 24 months (MD 12.91, 95% CI 7.55 to 18.29; 2 studies, 302 participants; low-certainty evidence) and 36 months (MD 6.64, 95% CI 1.54 to 11.75; 1 study, 806 participants; low-certainty evidence). For longest period of abstinence (LPA), AA/TSF may perform as well as comparison interventions at six months (MD 0.60, 95% CI -0.30 to 1.50; 2 studies, 136 participants; low-certainty evidence). For drinking intensity, AA/TSF may perform as well as other clinical interventions at 12 months, as measured by drinks per drinking day (DDD) (MD -0.17, 95% CI -1.11 to 0.77; 1 study, 1516 participants; moderate-certainty evidence) and percentage days heavy drinking (PDHD) (MD -5.51, 95% CI -14.15 to 3.13; 1 study, 91 participants; low-certainty evidence). For alcohol-related consequences, AA/TSF probably performs as well as other clinical interventions at 12 months (MD -2.88, 95% CI -6.81 to 1.04; 3 studies, 1762 participants; moderate-certainty evidence). For alcohol addiction severity, one study found evidence of a difference in favor of AA/TSF at 12 months (P < 0.05; low-certainty evidence). AA/TSF (non-manualized) compared to treatments with a different theoretical orientation (e.g. CBT) (randomized/quasi-randomized evidence) For the proportion of participants completely abstinent, non-manualized AA/TSF may perform as well as other clinical interventions at three to nine months follow-up (RR 1.71, 95% CI 0.70 to 4.18; 1 study, 93 participants; low-certainty evidence). Non-manualized AA/TSF may also perform slightly better than other clinical interventions for PDA (MD 3.00, 95% CI 0.31 to 5.69; 1 study, 93 participants; low-certainty evidence). For drinking intensity, AA/TSF may perform as well as other clinical interventions at nine months, as measured by DDD (MD -1.76, 95% CI -2.23 to -1.29; 1 study, 93 participants; very low-certainty evidence) and PDHD (MD 2.09, 95% CI -1.24 to 5.42; 1 study, 286 participants; low-certainty evidence). None of the RCTs comparing non-manualized AA/TSF to other clinical interventions assessed LPA, alcohol-related consequences, or alcohol addiction severity. Cost-effectiveness studies In three studies, AA/TSF had higher healthcare cost savings than outpatient treatment, CBT, and no AA/TSF treatment. The fourth study found that total medical care costs decreased for participants attending CBT, MET, and AA/TSF treatment, but that among participants with worse prognostic characteristics AA/TSF had higher potential cost savings than MET (moderate-certainty evidence). Authors' conclusions: There is high quality evidence that manualized AA/TSF interventions are more effective than other established treatments, such as CBT, for increasing abstinence. Non-manualized AA/TSF may perform as well as these other established treatments. AA/TSF interventions, both manualized and non-manualized, may be at least as effective as other treatments for other alcohol-related outcomes. AA/TSF probably produces substantial healthcare cost savings among people with alcohol use disorder.

The Cochrane database of systematic reviews · meta-analysis · 192 citationsread the source →

Intrinsic functional connectivity differentiates minimally conscious from unresponsive patients.

Despite advances in resting state functional magnetic resonance imaging investigations, clinicians remain with the challenge of how to implement this paradigm on an individualized basis. Here, we assessed the clinical relevance of resting state functional magnetic resonance imaging acquisitions in patients with disorders of consciousness by means of a systems-level approach. Three clinical centres collected data from 73 patients in minimally conscious state, vegetative state/unresponsive wakefulness syndrome and coma. The main analysis was performed on the data set coming from one centre (Liège) including 51 patients (26 minimally conscious state, 19 vegetative state/unresponsive wakefulness syndrome, six coma; 15 females; mean age 49 ± 18 years, range 11-87; 16 traumatic, 32 non-traumatic of which 13 anoxic, three mixed; 35 patients assessed >1 month post-insult) for whom the clinical diagnosis with the Coma Recovery Scale-Revised was congruent with positron emission tomography scanning. Group-level functional connectivity was investigated for the default mode, frontoparietal, salience, auditory, sensorimotor and visual networks using a multiple-seed correlation approach. Between-group inferential statistics and machine learning were used to identify each network's capacity to discriminate between patients in minimally conscious state and vegetative state/unresponsive wakefulness syndrome. Data collected from 22 patients scanned in two other centres (Salzburg: 10 minimally conscious state, five vegetative state/unresponsive wakefulness syndrome; New York: five minimally conscious state, one vegetative state/unresponsive wakefulness syndrome, one emerged from minimally conscious state) were used to validate the classification with the selected features. Coma Recovery Scale-Revised total scores correlated with key regions of each network reflecting their involvement in consciousness-related processes. All networks had a high discriminative capacity (>80%) for separating patients in a minimally conscious state and vegetative state/unresponsive wakefulness syndrome. Among them, the auditory network was ranked the most highly. The regions of the auditory network which were more functionally connected in patients in minimally conscious state compared to vegetative state/unresponsive wakefulness syndrome encompassed bilateral auditory and visual cortices. Connectivity values in these three regions discriminated congruently 20 of 22 independently assessed patients. Our findings point to the significance of preserved abilities for multisensory integration and top-down processing in minimal consciousness seemingly supported by auditory-visual crossmodal connectivity, and promote the clinical utility of the resting paradigm for single-patient diagnostics.

Brain : a journal of neurology · cohort or longitudinal · 283 citationsread the source →

Mental Health in Adolescents with a Migration Background in 29 European Countries: The Buffering Role of Social Capital.

Previous research is inconclusive as to whether having an immigration background acts as a risk factor for poor mental health in adolescents, and furthermore, what contribution the social context in which adolescents grow up may make. To address these questions, the current study uses an integrative resilience framework to investigate the association between immigration background and adolescent mental health, and the moderating role of social capital at the individual, the school, and the national level. The study uses data gathered from nationally representative samples of adolescents aged 11, 13, and 15 years (Ngirls = 63,425 (52.1%); Mage = 13.57, SD = 1.64) from 29 countries participating in the 2017/18 Health Behaviour in School-aged Children (HBSC) study. Data analysis reveals that first- and second-generation immigrants reported higher levels of life dissatisfaction and psychosomatic symptoms than their native peers, and that this association varied across schools and countries. In addition, social capital was found to moderate the association between immigration background and adolescent mental health. Individual-level social support from peers and family and national-level trust protected against poor mental health in adolescents with an immigration background, while the opposite was true for individual-level teacher support. Supportive teacher-student relationships were found to provide more protection against poor mental health for native adolescents than for immigrant adolescents. Our findings indicate the importance of taking an ecological approach to design interventions to reduce the negative effects of having an immigration background on adolescent mental health.

Journal of youth and adolescence · 40 citationsread the source →

Trajectories of Screen Time across Adolescence and Their Associations with Adulthood Mental Health and Behavioral Outcomes.

Excessive screen time among adolescents is discussed as a significant public health concern. Identifying adolescent longitudinal patterns of time spent on regularly-used media screens and understanding their young adulthood mental health and behavioral issue correlates may help inform strategies for improving these outcomes. This study aimed to characterize joint developmental patterns of time spent on videogames, surfing/chatting the Internet, and TV/DVDs during adolescence (at ages 11, 13, 15, 17) and their associations with mental health (i.e., depression, anxiety, suicidal ideation, and self-injury) and behavioral issues (i.e., substance use, delinquency, aggression) in early adulthood (at age 20). A parallel-process latent class growth analysis was used to model data from a diverse community-ascertained sample of youth in Zurich, Switzerland (n = 1521; 51.7% males). Results suggested that a five-class model best fitted the data: (1) low-screen use, 37.6%; (2) increasing chatting/surfing, 24.0%; (3) moderate-screen use, 18.6%; (4) early-adolescence screen use, 9.9%; and (5) increasing videogame and chatting/surfing, 9.9%. After adjusting for baseline levels of outcomes (primarily at age 11), the trajectory groups differed in their associations with adulthood outcomes of mental health and behavioral problems, indicating the importance of problematic screen usage patterns in predicting these outcomes. Future research to test the directionality of these associations will be important. These findings suggest which patterns of screen use may be a marker for later mental health and behavioral issues in different domains.

Journal of youth and adolescence · 20 citationsread the source →

Problematic Social Media Use and Health among Adolescents.

(1) Background: The use of social media has become an integral part of adolescents' daily lives. However, the intensive use of social media can develop into a health-threatening addiction, but unfavourable health consequences can occur even with less use. Social media user groups categorized as no-risk, moderate risk (of developing problematic behaviour), and problematic use were examined with reference to their prevalence, their associations with individual determinants and health, and the increased health risk between groups. (2) Methods: The Finnish nationally representative HBSC data (persons aged 11, 13, and 15, n = 3408) and descriptive and binary logistic regression analysis were applied. (3) Results: Problematic social media use (9.4%) was most common among older age groups, and among persons with moderate/low school achievement, low health literacy, and low parental monitoring. Belonging to a moderate risk group (33.5%) was most frequent among girls, and among adolescents with low/moderate parental monitoring and health literacy. All the negative health indicators systematically increased if the respondent belonged to a moderate risk or problematic use group. (4) Conclusions: The study confirmed the association between problematic social media use and negative health outcomes and highlighted the need to pay close attention to adolescents at moderate risk who exhibited negative health outcomes.

International journal of environmental research and public health · 66 citationsread the source →