One query across six libraries. Commentary sits inside the verse it comments on.
How this query's results fall across the libraries. It redraws with every search.
Sound narrations only. Anchored texts rank first.
وَقَالَ لَنَا أَبُو الْوَلِيدِ حَدَّثَنَا حَمَّادُ بْنُ سَلَمَةَ، عَنْ ثَابِتٍ، عَنْ أَنَسٍ، عَنْ أُبَىٍّ، قَالَ كُنَّا نَرَى هَذَا مِنَ الْقُرْآنِ حَتَّى نَزَلَتْ {أَلْهَاكُمُ التَّكَاثُرُ}
Ubayy said (referring to the hadith above), "We considered this as a saying from the Qur'an till the Surah (beginning with):"The mutual rivalry (for piling up of worldly things) diverts you' (102:1) was revealed
Peer-reviewed works with DOI and abstract, discovered from MEDLINE-indexed literature. Candidates: no tier, no stated finding, not yet read.
A randomized controlled trial of MoodSwings 2.0: An internet-based self-management program for bipolar disorder.
Objectives: MoodSwings 2.0 is an online self-guided intervention for bipolar disorder that includes educational modules, interactive tools, and discussion forums. The primary aim of the study was to determine if participation in MoodSwings 2.0 would result in decreased symptoms of depression and mania compared to the control condition. Secondary aims were to identify improvements in core depression symptoms, quality of life, medication adherence, functioning, and time to relapse. Methods: This was a three-arm randomized controlled trial that compared two intervention arms against a peer support control group (forum). A total of 304 adults aged 21 to 65 years with a diagnosis of bipolar disorder were assigned to a forum-only control group (Group 1; n = 102), a forum plus modules treatment group (Group 2; n = 102), or a forum, modules, and tools treatment group (Group 3; n = 100), in addition to usual care. Results: There was a significant intervention impact showing improvement on the primary outcome of depression for Group 2 compared to Group 1 (P = .05) with effect sizes (Cohen's d) ranging from 0.17 to 0.43. There was also a significant intervention impact showing improvement on the secondary outcome of core depression for Group 2 (P = .02) and Group 3 (P = .05), but worse physical functioning for Group 3 (P = .01), compared to Group 1. Conclusions: This study provides evidence of the efficacy of internet-based psychoeducation interventions for bipolar disorder in reducing depressive symptoms. Further investigation is needed to assess effectiveness in a public program.
Mindfulness for smoking cessation.
Background: Mindfulness-based smoking cessation interventions may aid smoking cessation by teaching individuals to pay attention to, and work mindfully with, negative affective states, cravings, and other symptoms of nicotine withdrawal. Types of mindfulness-based interventions include mindfulness training, which involves training in meditation; acceptance and commitment therapy (ACT); distress tolerance training; and yoga. Objectives: To assess the efficacy of mindfulness-based interventions for smoking cessation among people who smoke, and whether these interventions have an effect on mental health outcomes. Search methods: We searched the Cochrane Tobacco Addiction Group's specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, and trial registries to 15 April 2021. We also employed an automated search strategy, developed as part of the Human Behaviour Change Project, using Microsoft Academic. Selection criteria: We included randomised controlled trials (RCTs) and cluster-RCTs that compared a mindfulness-based intervention for smoking cessation with another smoking cessation programme or no treatment, and assessed smoking cessation at six months or longer. We excluded studies that solely recruited pregnant women. Data collection and analysis: We followed standard Cochrane methods. We measured smoking cessation at the longest time point, using the most rigorous definition available, on an intention-to-treat basis. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) for smoking cessation for each study, where possible. We grouped eligible studies according to the type of intervention and type of comparator. We carried out meta-analyses where appropriate, using Mantel-Haenszel random-effects models. We summarised mental health outcomes narratively. Main results: We included 21 studies, with 8186 participants. Most recruited adults from the community, and the majority (15 studies) were conducted in the USA. We judged four of the studies to be at low risk of bias, nine at unclear risk, and eight at high risk. Mindfulness-based interventions varied considerably in design and content, as did comparators, therefore, we pooled small groups of relatively comparable studies. We did not detect a clear benefit or harm of mindfulness training interventions on quit rates compared with intensity-matched smoking cessation treatment (RR 0.99, 95% CI 0.67 to 1.46; I2 = 0%; 3 studies, 542 participants; low-certainty evidence), less intensive smoking cessation treatment (RR 1.19, 95% CI 0.65 to 2.19; I2 = 60%; 5 studies, 813 participants; very low-certainty evidence), or no treatment (RR 0.81, 95% CI 0.43 to 1.53; 1 study, 325 participants; low-certainty evidence). In each comparison, the 95% CI encompassed benefit (i.e. higher quit rates), harm (i.e. lower quit rates) and no difference. In one study of mindfulness-based relapse prevention, we did not detect a clear benefit or harm of the intervention over no treatment (RR 1.43, 95% CI 0.56 to 3.67; 86 participants; very low-certainty evidence). We did not detect a clear benefit or harm of ACT on quit rates compared with less intensive behavioural treatments, including nicotine replacement therapy alone (RR 1.27, 95% CI 0.53 to 3.02; 1 study, 102 participants; low-certainty evidence), brief advice (RR 1.27, 95% CI 0.59 to 2.75; 1 study, 144 participants; very low-certainty evidence), or less intensive ACT (RR 1.00, 95% CI 0.50 to 2.01; 1 study, 100 participants; low-certainty evidence). There was a high level of heterogeneity (I2 = 82%) across studies comparing ACT with intensity-matched smoking cessation treatments, meaning it was not appropriate to report a pooled result. We did not detect a clear benefit or harm of distress tolerance training on quit rates compared with intensity-matched smoking cessation treatment (RR 0.87, 95% CI 0.26 to 2.98; 1 study, 69 participants; low-certainty evidence) or less intensive smoking cessation treatment (RR 1.63, 95% CI 0.33 to 8.08; 1 study, 49 participants; low-certainty evidence). We did not detect a clear benefit or harm of yoga on quit rates compared with intensity-matched smoking cessation treatment (RR 1.44, 95% CI 0.40 to 5.16; 1 study, 55 participants; very low-certainty evidence). Excluding studies at high risk of bias did not substantially alter the results, nor did using complete case data as opposed to using data from all participants randomised. Nine studies reported on changes in mental health and well-being, including depression, anxiety, perceived stress, and negative and positive affect. Variation in measures and methodological differences between studies meant we could not meta-analyse these data. One study found a greater reduction in perceived stress in participants who received a face-to-face mindfulness training programme versus an intensity-matched programme. However, the remaining eight studies found no clinically meaningful differences in mental health and well-being between participants who received mindfulness-based treatments and participants who received another treatment or no treatment (very low-certainty evidence). Authors' conclusions: We did not detect a clear benefit of mindfulness-based smoking cessation interventions for increasing smoking quit rates or changing mental health and well-being. This was the case when compared with intensity-matched smoking cessation treatment, less intensive smoking cessation treatment, or no treatment. However, the evidence was of low and very low certainty due to risk of bias, inconsistency, and imprecision, meaning future evidence may very likely change our interpretation of the results. Further RCTs of mindfulness-based interventions for smoking cessation compared with active comparators are needed. There is also a need for more consistent reporting of mental health and well-being outcomes in studies of mindfulness-based interventions for smoking cessation.
Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: a randomised controlled, open-label, multicentre trial.
Background: Treatment of patients with ileocaecal Crohn's disease who have not responded to conventional therapy is commonly scaled up to biological agents, but surgery can also offer excellent short-term and long-term results. We compared laparoscopic ileocaecal resection with infliximab to assess how they affect health-related quality of life. Methods: In this randomised controlled, open-label trial, in 29 teaching hospitals and tertiary care centres in the Netherlands and the UK, adults with non-stricturing, ileocaecal Crohn's disease, in whom conventional therapy has failed were randomly allocated (1:1) by an internet randomisation module with biased-coin minimisation for participating centres and perianal fistula to receive laparoscopic ileocaecal resection or infliximab. Eligible patients were aged 18-80 years, had active Crohn's disease of the terminal ileum, and had not responded to at least 3 months of conventional therapy with glucocorticosteroids, thiopurines, or methotrexate. Patients with diseased terminal ileum longer than 40 cm or abdominal abscesses were excluded. The primary outcome was quality of life on the Inflammatory Bowel Disease Questionnaire (IBDQ) at 12 months. Secondary outcomes were general quality of life, measured by the Short Form-36 (SF-36) health survey and its physical and mental component subscales, days unable to participate in social life, days on sick leave, morbidity (additional procedures and hospital admissions), and body image and cosmesis. Analyses of the primary outcome were done in the intention-to-treat population, and safety analyses were done in the per-protocol population. This trial is registered at the Dutch Trial Registry (NTR1150). Findings: Between May 2, 2008, and October 14, 2015, 73 patients were allocated to have resection and 70 to receive infliximab. Corrected for baseline differences, the mean IBDQ score at 12 months was 178·1 (95% CI 171·1-185·0) in the resection group versus 172·0 (164·3-179·6) in the infliximab group (mean difference 6·1 points, 95% CI -4·2 to 16·4; p=0·25). At 12 months, the mean SF-36 total score was 112·1 (95% CI 108·0-116·2) in the resection group versus 106·5 (102·1-110·9) in the infliximab group (mean difference 5·6, 95% CI -0·4 to 11·6), the mean physical component score was 47·7 (45·7-49·7) versus 44·6 (42·5-46·8; mean difference 3·1, 4·2 to 6·0), and the mean mental component score was 49·5 (47·0-52·1) versus 46·1 (43·3-48·9; mean difference 3·5, -0·3 to 7·3). Mean numbers of days of sick leave were 3·4 days (SD 7·1) in the resection group versus 1·4 days (4·7) in the infliximab group (p<0·0001), days not able to take part in social life were 1·8 days (6·3) versus 1·1 days (4·5; p=0·20), days of scheduled hospital admission were 6·5 days (3·8) versus 6·8 days (3·2; p=0·84), and the number of patients who had unscheduled hospital admissions were 13 (18%) of 73 versus 15 (21%) of 70 (p=0·68). Body-image scale mean scores in the patients who had resection were 16·0 (95% CI 15·2-16·8) at baseline versus 17·8 (17·1-18·4) at 12 months, and cosmetic scale mean scores were 17·6 (16·6-18·6) versus 18·6 (17·6-19·6). Surgical intervention-related complications classified as IIIa or worse on the Clavien-Dindo scale occurred in four patients in the resection group. Treatment-related serious adverse events occurred in two patients in the infliximab group. During a median follow-up of 4 years (IQR 2-6), 26 (37%) of 70 patients in the infliximab group had resection, and 19 (26%) of 73 patients in the resection group received anti-TNF. Interpretation: Laparoscopic resection in patients with limited (diseased terminal ileum <40 cm), non-stricturing, ileocaecal Crohn's disease in whom conventional therapy has failed could be considered a reasonable alternative to infliximab therapy. Funding: Netherlands Organisation for Health Research and Development.
Palliative Care Phase: inter-rater reliability and acceptability in a national study.
Background: The concept of palliative care consisting of five distinct, clinically meaningful, phases (stable, unstable, deteriorating, terminal and bereavement) was developed in Australia about 20 years ago and is used routinely for communicating clinical status, care planning, quality improvement and funding. Aim: To test the reliability and acceptability of revised definitions of Palliative Care Phase. Design: Multi-centre cross-sectional study involving pairs of clinicians independently rating patients according to revised definitions of Palliative Care Phase. Setting/participants: Clinicians from 10 Australian palliative care services, including 9 inpatient units and 1 mixed inpatient/community-based service. Results: A total of 102 nursing and medical clinicians participated, undertaking 595 paired assessments of 410 patients, of which 90.7% occurred within 2 h. Clinicians rated 54.8% of patients in the stable phase, 15.8% in the unstable phase, 20.8% in the deteriorating phase and 8.7% in the terminal phase. Overall agreement between clinicians' rating of Palliative Care Phase was substantial (kappa = 0.67; 95% confidence interval = 0.61-0.70). A moderate level of inter-rater reliability was apparent across all participating sites. The results indicated that Palliative Care Phase was an acceptable measure, with no significant difficulties assigning patients to a Palliative Care Phase and a good fit between assessment of phase and the definition of that phase. The most difficult phase to distinguish from other phases was the deteriorating phase. Conclusion: Policy makers, funders and clinicians can be confident that Palliative Care Phase is a reliable and acceptable measure that can be used for care planning, quality improvement and funding purposes.
Is structured group psychoeducation for bipolar patients effective in ordinary mental health services? A controlled trial in Italy.
Background: Recent reviews of evidence-based guidelines for the clinical management of Bipolar Disorders (BD) have recommended that "all patients with BD be offered group or individual psychoeducation" to prevent relapse, improve treatment adherence, quality of life, and functioning. The present study evaluated the effectiveness of psychoeducation in routine mental health services in reducing number of hospitalisations and number of days spent in hospital, at a 1-year follow-up. Methods: A total of 102 outpatients were recruited from two Italian Departments of Mental Health. Inclusion criteria were a lifetime BD type I or II diagnosis, assessed with SCID, and ≥ 3 months of euthymia. Exclusion criteria were DSM-IV Axis I comorbidity, mental retardation (IQ<70), organic brain damage, or deafness. All participants received standard psychiatric care, including standard pharmacological treatment; the experimental group also received 21 group psychoeducation sessions, weekly held and conducted according to Colom and Vieta's model. Results: The number of patients hospitalised during the 1-year follow-up, the mean number of hospitalisations per patient, and the mean number of hospitalisation days were significantly lower for psychoeducated patients. Conclusion: Our findings support the view that group psychoeducation is an effective way to prevent hospitalisation and decrease hospital days in pharmacologically treated patients with bipolar disorder also in routine clinical settings. The results confirm that psychoeducation promotes improvement in illness course by preventing acute phases and enhancing mood stability, and consequently, improvement in the quality of life for people with BD.
Cognitive behavioural therapy for insomnia (CBTi) as a treatment for tinnitus-related insomnia: a randomised controlled trial.
Insomnia is a significant difficulty and is reported by large proportion of people with tinnitus. Although cognitive behavioural therapy for insomnia (CBTi) might be an effective treatment, no controlled studies had been conducted to date. This randomised controlled trial evaluated the benefits of CBTi on a sample of 102 people with tinnitus-related insomnia. Participants were randomised to 1) CBTi, 2) Audiology-Based Care (ABC) or 3) Sleep Support Group (SSG). Primary outcomes included insomnia, sleep efficiency and total sleep time. Secondary outcomes measured sleep onset latency, sleep quality, tinnitus distress, psychological distress, functioning and quality of life. CBTi was superior at reducing insomnia and increasing sleep efficiency compared to ABC post-intervention and at 6-month follow-up. ABC was superior at reducing insomnia and increasing sleep efficiency compared to SSG. Both CBTi and ABC reported increased total sleep time compared to SSG at 6-month follow. More than 80% of participants in the CBTi group reported clinically meaningful improvements compared to 47% in ABC and 20% for those receiving social support. CBTi was more effective in reducing tinnitus distress and improving sleep quality, functioning and some aspects of mental health. CBTi and ABC offer effective treatments for tinnitus-related sleep disorder but CBTi offers a sizeable benefit.
Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions.
Major depression is a debilitating psychiatric illness that is typically associated with low mood and anhedonia. Depression has a heritable component that has remained difficult to elucidate with current sample sizes due to the polygenic nature of the disorder. To maximize sample size, we meta-analyzed data on 807,553 individuals (246,363 cases and 561,190 controls) from the three largest genome-wide association studies of depression. We identified 102 independent variants, 269 genes, and 15 genesets associated with depression, including both genes and gene pathways associated with synaptic structure and neurotransmission. An enrichment analysis provided further evidence of the importance of prefrontal brain regions. In an independent replication sample of 1,306,354 individuals (414,055 cases and 892,299 controls), 87 of the 102 associated variants were significant after multiple testing correction. These findings advance our understanding of the complex genetic architecture of depression and provide several future avenues for understanding etiology and developing new treatment approaches.
Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study.
Background: Global estimates of the effect of common modifiable risk factors on cardiovascular disease and mortality are largely based on data from separate studies, using different methodologies. The Prospective Urban Rural Epidemiology (PURE) study overcomes these limitations by using similar methods to prospectively measure the effect of modifiable risk factors on cardiovascular disease and mortality across 21 countries (spanning five continents) grouped by different economic levels. Methods: In this multinational, prospective cohort study, we examined associations for 14 potentially modifiable risk factors with mortality and cardiovascular disease in 155 722 participants without a prior history of cardiovascular disease from 21 high-income, middle-income, or low-income countries (HICs, MICs, or LICs). The primary outcomes for this paper were composites of cardiovascular disease events (defined as cardiovascular death, myocardial infarction, stroke, and heart failure) and mortality. We describe the prevalence, hazard ratios (HRs), and population-attributable fractions (PAFs) for cardiovascular disease and mortality associated with a cluster of behavioural factors (ie, tobacco use, alcohol, diet, physical activity, and sodium intake), metabolic factors (ie, lipids, blood pressure, diabetes, obesity), socioeconomic and psychosocial factors (ie, education, symptoms of depression), grip strength, and household and ambient pollution. Associations between risk factors and the outcomes were established using multivariable Cox frailty models and using PAFs for the entire cohort, and also by countries grouped by income level. Associations are presented as HRs and PAFs with 95% CIs. Findings: Between Jan 6, 2005, and Dec 4, 2016, 155 722 participants were enrolled and followed up for measurement of risk factors. 17 249 (11·1%) participants were from HICs, 102 680 (65·9%) were from MICs, and 35 793 (23·0%) from LICs. Approximately 70% of cardiovascular disease cases and deaths in the overall study population were attributed to modifiable risk factors. Metabolic factors were the predominant risk factors for cardiovascular disease (41·2% of the PAF), with hypertension being the largest (22·3% of the PAF). As a cluster, behavioural risk factors contributed most to deaths (26·3% of the PAF), although the single largest risk factor was a low education level (12·5% of the PAF). Ambient air pollution was associated with 13·9% of the PAF for cardiovascular disease, although different statistical methods were used for this analysis. In MICs and LICs, household air pollution, poor diet, low education, and low grip strength had stronger effects on cardiovascular disease or mortality than in HICs. Interpretation: Most cardiovascular disease cases and deaths can be attributed to a small number of common, modifiable risk factors. While some factors have extensive global effects (eg, hypertension and education), others (eg, household air pollution and poor diet) vary by a country's economic level. Health policies should focus on risk factors that have the greatest effects on averting cardiovascular disease and death globally, with additional emphasis on risk factors of greatest importance in specific groups of countries. Funding: Full funding sources are listed at the end of the paper (see Acknowledgments).
Prevalence of antenatal and postnatal anxiety: systematic review and meta-analysis.
BackgroundMaternal anxiety negatively influences child outcomes. Reliable estimates have not been established because of varying published prevalence rates. AimsTo establish summary estimates for the prevalence of maternal anxiety in the antenatal and postnatal periods. MethodWe searched multiple databases including MEDLINE, Embase, and PsycINFO to identify studies published up to January 2016 with data on the prevalence of antenatal or postnatal anxiety. Data were extracted from published reports and any missing information was requested from investigators. Estimates were pooled using random-effects meta-analyses. ResultsWe reviewed 23 468 abstracts, retrieved 783 articles and included 102 studies incorporating 221 974 women from 34 countries. The prevalence for self-reported anxiety symptoms was 18.2% (95% CI 13.6-22.8) in the first trimester, 19.1% (95% CI 15.9-22.4) in the second trimester and 24.6% (95% CI 21.2-28.0) in the third trimester. The overall prevalence for a clinical diagnosis of any anxiety disorder was 15.2% (95% CI 9.0-21.4) and 4.1% (95% CI 1.9-6.2) for a generalised anxiety disorder. Postnatally, the prevalence for anxiety symptoms overall at 1-24 weeks was 15.0% (95% CI 13.7-16.4). The prevalence for any anxiety disorder over the same period was 9.9% (95% CI 6.1-13.8), and 5.7% (95% CI 2.3-9.2) for a generalised anxiety disorder. Rates were higher in low- to middle-income countries. ConclusionsResults suggest perinatal anxiety is highly prevalent and merits clinical attention. Research is warranted to develop evidence-based interventions.
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 role of self-criticism, dependency, and hassles in the course of depressive illness: a multiwave longitudinal study.
The current study utilized a multiwave longitudinal design to examine whether dependency and/or self-criticism influence the course of depressive symptoms in a community sample of adults with a history of major depression. In addition, the authors examined whether self-esteem serves as a buffer against the development of depressive symptoms following increases in hassles in individuals possessing such traits. At Time 1, 102 participants completed measures assessing depressive symptoms, self-criticism, dependency, and self-esteem. Every 6 weeks for the next year, participants completed measures assessing depressive symptoms and hassles. High self-criticism was associated with greater elevations in depressive symptoms following elevations in hassles in low but not high-self-esteem individuals. Results with respect to dependency, however, were contrary to hypotheses. High dependency was associated with elevations in depressive symptoms following elevations in hassles in high-self-esteem individuals. In contrast, high dependency was associated with chronically elevated depressive symptoms in low-self-esteem individuals.
Microsurgical denervation of the spermatic cord for chronic orchialgia: long-term results from a single center.
Purpose: We assessed the long-term efficacy, complications and patient perceptions of microsurgical denervation of the spermatic cord in the treatment of chronic orchialgia. Materials and methods: Microsurgical denervation of the spermatic cord was performed on 95 testicular units in 79 men (mean age 40.3 years, mean duration of pain 62 months, 16 bilateral) for chronic orchialgia. Conservative management failed in all, and patients were evaluated with an extensive medical history and physical examination. To be a candidate for microsurgical denervation of the spermatic cord each man would have responded either completely or partially to spermatic cord block (greater than 50% decrease in pain) and had no identifiable reversible etiology. Postoperative pain rating scales (0 to 10) were used to determine efficacy. Results: Mean followup was 20.3 months (range 1 to 102 months) and complete, durable relief was noted in 67 (71%) testicular units, partial relief in 17 (17%), and unchanged in 11 (12%). No patients reported worse pain. Complications included testicular atrophy without hypogonadism in 2 patients, superficial wound infection in 2, hydrocele in 2 and an incisional hematoma in 1. Conclusions: Microsurgical denervation of the spermatic cord is a minimally invasive, effective and durable management option for treatment of chronic orchialgia refractory to medical management, preserving the physiological function and psychological role of the testes.
Fitting in matters: markers of in-group belonging and academic outcomes.
Minority boys are at risk of academic disengagement. Prior research documents that an aspect of racial-ethnic identity, in-group connection, can buffer against this risk, but that in-group connection is undermined in high-risk neighborhoods. We examined another way that boys may feel connected to the in-group, by looking like in-group members. We hypothesize that physical markers of in-group membership can serve to improve boys' sense of belongingness, thereby facilitating their engagement in school. We tested our model with low-income, high-risk African American (Study 1, n= 102) and Latino (Study 2, n= 66) teens. Hierarchical regression supported our model; dark skin tone was a protective factor (and light skin tone a risk factor) for African American boys, and feeling that one looks Latino was a protective factor (and feeling that one does not look Latino a risk factor) for Latino boys' grades, in-class behavior, and school engagement. Mediational analyses suggest that markers of belongingness have their impact via peer-group choice.
Approaches to the assessment of adherence to CBT-I, predictors of adherence, and the association of adherence to outcomes: A systematic review.
This systematic review (PROSPERO registration CRD42020158010) aimed to: 1) assess how adherence to cognitive behavioural therapy for insomnia (CBT-I) has been measured; 2) evaluate predictors of adherence; and 3) determine whether treatment outcome is associated with adherence. Inclusion criteria included: adults with insomnia; an intervention of CBT-I, including sleep restriction and/or stimulus control; a reported measure of adherence; and written in English. Searches of eight databases returned 2038 publications as of April 2021. The final sample included 102 papers. Publication quality and risk of bias were assessed using Joanna Briggs institute tools. Studies assessed either global adherence or adherence to specific components of CBT-I via questionnaires, sleep diaries, interviews or actigraphy. Twenty-eight papers examined predictors of adherence. Better pre- and post-session sleep, greater psychosocial support, increased self-efficacy, and fewer dysfunctional beliefs about sleep predicted greater adherence. Twenty-eight papers examined whether adherence predicted treatment outcomes. Only insomnia severity index scores post-treatment were consistently predicted by adherence, and only by a few measures of adherence. Overall, there was very little consistency in how adherence was measured, and in predictors and outcome variables assessed. A standardised method for assessing specific adherence constructs is indicated, to fully understand the role of adherence in CBT-I.
Effectiveness of counseling for anxiety and depression in mothers of children ages 0-30 months by community workers in Karachi, Pakistan: a quasi experimental study.
Background: The prevalence of anxiety/depression is quite high during the perinatal period but unfortunately its detection and treatment have been less than satisfactory. Moreover, many women are reluctant to take pharmacotherapy for fear of excretion of drugs into their breast milk. This study assesses the effectiveness of counseling from minimally trained community health workers in reducing anxiety/depression, the rate of recurrence and the interval preceding recurrence in women during first two and a half years after childbirth. Methods: In a quasi-experimental study, community women from two under-privileged communities were trained in data gathering, teaching healthy child-rearing practices, basic counseling skills, and screening for anxiety/depression by using an indigenously developed questionnaire, the Aga Khan University Anxiety and Depression Scale (AKUADS). The diagnosis was further confirmed by a clinical psychologist using DSM IV criteria. After obtaining consent, 420 women were screened and 102 were identified as having anxiety/depression. Screening was carried out after 1, 2, 6, 12, 18, 24 and 30 months of a live birth. Only 62 out of 102 agreed to be counseled and received eight weekly sessions. AKUADS was re-administered at 4 weeks and 8 weeks after the beginning of counseling; this was followed by the clinical psychologist's interview for confirmation of response. After recovery, screening was continued every 3 months for detection of recurrence throughout the study period. Out of the women who had declined counseling 12 agreed to retake AKUADS after 4 and 8 weeks of diagnosis. Independent samples t-test, chi-square test, Repeated Measures ANOVA and Kaplan Meier technique were used for the analysis. Results: A significant decline in level of anxiety/depression was found in both the counseled and the non-counseled groups at 4 and 8 weeks (p-value < 0.001) but the counseled group fared better than the non-counseled for recovery, reduction in the rate of recurrence and increase in the duration before relapse. Conclusions: As our results cannot be generalized; further studies need to be carried out, to assess the benefit of incorporating minimal counseling skills in the training of community health workers.
Comparative effectiveness of cognitive behavioural therapy, modafinil, and their combination for treating fatigue in multiple sclerosis (COMBO-MS): a randomised, statistician-blinded, parallel-arm trial.
Background: Fatigue is one of the most disabling symptoms reported by people with multiple sclerosis. Although behavioural and pharmacological interventions might be partly beneficial, their combined effects have not been evaluated for multiple sclerosis fatigue, or examined with sufficient consideration of characteristics that might affect treatment response. In this comparative effectiveness research trial, we compared the effectiveness of cognitive behavioural therapy (CBT), modafinil, and their combination for treating multiple sclerosis fatigue. Methods: This randomised, analyst-blinded, parallel-arm, comparative effectiveness trial was done at two universities in the USA. Adults (aged ≥18 years) with multiple sclerosis and problematic fatigue (Fatigue Severity Scale [FSS] score ≥4) were randomly assigned (1:1:1), using a web-based treatment assignment system with minimisation, to receive CBT, modafinil, or both for 12 weeks. Statisticians were masked to group assignment, but participants, study neurologists, CBT interventionalists, and coordinators were not masked to treatment assignment. The primary outcome was the change in Modified Fatigue Impact Scale (MFIS) from baseline to 12 weeks, assessed using multiple linear regression, adjusted for age, sex, study site, anxiety, pain, baselines MFIS score, and physical activity. Analyses were done by intent to treat. The trial was registered with clinicaltrials.gov, NCT03621761, and is completed. Findings: Between Nov 15, 2018, and June 2, 2021, 336 participants were randomly assigned treatment (114 assigned to CBT, 114 assigned to modafinil, and 108 assigned to combination therapy). At 12 weeks, CBT (n=103), modafinil (n=107), and combination therapy (n=102) were associated with clinically meaningful within-group MFIS reductions of 15·20 (SD 11·90), 16·90 (15·90), and 17·30 (16·20) points, respectively. Change in MFIS scores from baseline to 12 weeks did not differ between groups: relative to combination therapy, the adjusted total mean difference in MFIS change score was 1·88 (95% CI -2·21 to 5·96) for CBT and 1·20 (-2·83 to 5·23) for modafinil. Most common adverse events for modafinil-containing treatment groups included insomnia (eight [7%] for modafinil and eight [7%] for combination therapy) and anxiety (three [3%] for modafinil and nine [8%] for combination therapy). Interpretation: Modafinil, CBT, and combination therapy were associated with similar reductions in the effects of multiple sclerosis fatigue at 12 weeks. Combination therapy was not associated with augmented improvement compared with the individual interventions. Further research is needed to determine whether effects of these interventions on multiple sclerosis-related fatigue is influenced by sleep hygiene and sleepiness. No serious adverse events related to the study drug were encountered. Funding: Patient-Centered Outcomes Research Institute and National Multiple Sclerosis Society.
Early liver transplantation for severe alcohol-related hepatitis not responding to medical treatment: a prospective controlled study.
Background: Early liver transplantation for severe alcohol-related hepatitis is an emerging treatment option. We aimed to assess the risk of alcohol relapse 2 years after early liver transplantation for alcohol-related hepatitis compared with liver transplantation for alcohol-related cirrhosis after at least 6 months of abstinence. Methods: We conducted a multicentre, non-randomised, non-inferiority, controlled study in 19 French and Belgian hospitals. All participants were aged 18 years or older. There were three groups of patients recruited prospectively: patients with severe alcohol-related hepatitis who did not respond to medical treatment and were eligible for early liver transplantation according to a new selection scoring system based on social and addiction items that can be quantified in points (early transplantation group); patients with alcohol-related cirrhosis listed for liver transplantation after at least 6 months of abstinence (standard transplantation group); patients with severe alcohol-related hepatitis not responding to medical treatment not eligible for early liver transplantation according to the selection score (not eligible for early transplantation group), this group did not enter any further liver transplantation processes. We also defined a historical control group of patients with severe alcohol-related hepatitis unresponsive to medical therapy and non-transplanted. The primary outcome was the non-inferiority of 2-year rate of alcohol relapse after transplantation in the early transplantation group compared with the standard transplantation group using the alcohol timeline follow back (TLFB) method and a prespecified non-inferiority margin of 10%. Secondary outcomes were the pattern of alcohol relapse, 2-year survival rate post-transplant in the early transplantation group compared with the standard transplantation group, and 2-year overall survival in the early transplantation group compared with patients in the not eligible for early transplantation group and historical controls. This trial is registered with ClinicalTrials.gov, NCT01756794. Findings: Between Dec 5, 2012, and June 30, 2016, we included 149 patients with severe alcohol-related hepatitis: 102 in the early transplantation group and 47 in the not eligible for early transplantation group. 129 patients were included in the standard transplantation group. 68 patients in the early transplantation group and 93 patients in the standard transplantation group received a liver transplant. 23 (34%) patients relapsed in the early transplantation group, and 23 (25%) patients relapsed in the standard transplantation group; therefore, the non-inferiority of early transplantation versus standard transplantation was not demonstrated (absolute difference 9·1% [95% CI -∞ to 21·1]; p=0·45). The 2-year rate of high alcohol intake was greater in the early transplantation group than the standard transplantation group (absolute difference 16·7% [95% CI 5·8-27·6]) The time spent drinking alcohol was not different between the two groups (standardised difference 0·24 [95% CI -0·07 to 0·55]), but the time spent drinking a large quantity of alcohol was higher in the early transplantation group than the standard transplantation group (standardised difference 0·50 [95% CI 0·17-0·82]). 2-year post-transplant survival was similar between the early transplantation group and the standard transplantation group (hazard ratio [HR] 0·87 [95% CI 0·33-2·26]); 2-year overall survival was higher in the early transplantation group than the not eligible for early transplantation group and historical controls (HR 0·27 [95% CI 0·16-0·47] and 0·21 [0·13-0·32]). Interpretation: We cannot conclude non-inferiority in terms of rate of alcohol relapse post-transplant between early liver transplantation and standard transplantation. High alcohol intake is more frequent after early liver transplantation. This prospective controlled study confirms the important survival benefit related to early liver transplantation for severe alcohol-related hepatitis; and this study provides objective data on survival and alcohol relapse to tailor the management of patients with severe alcohol-related hepatitis. Funding: The present study has been granted by the French Ministry of Health-Programme Hospitalier de Recherche Clinique 2010.
Self-help cognitive behavior therapy for working women with problematic hot flushes and night sweats (MENOS@Work): a multicenter randomized controlled trial.
Objective: The aim of the study was to examine the efficacy of an unguided, self-help cognitive behavior therapy (SH-CBT) booklet on hot flush and night sweat (HFNS) problem rating, delivered in a work setting. Methods: Women aged 45 to 60 years, having 10 or more problematic HFNS a week, were recruited to a multicenter randomized controlled trial, via the occupational health/human resources departments of eight organizations. Participants were 1:1 randomized to SH-CBT or no treatment waitlist control (NTWC). The primary outcome was HFNS problem rating; secondary outcomes included HFNS frequency, work and social adjustment, sleep, mood, beliefs and behaviors, and work-related variables (absence, performance, turnover intention, and work impairment due to presenteeism). Intention-to-treat analysis was used, and between-group differences estimated using linear mixed models. Results: A total of 124 women were randomly allocated to SH-CBT (n = 60) and NTWC (n = 64). 104 (84%) were assessed for primary outcome at 6 weeks and 102 (82%) at 20 weeks. SH-CBT significantly reduced HFNS problem rating at 6 weeks (SH-CBT vs NTWC adjusted mean difference, -1.49; 95% CI, -2.11 to -0.86; P < 0.001) and at 20 weeks (-1.09; 95% CI, -1.87 to -0.31; P < 0.01). SH-CBT also significantly reduced HFNS frequency, improved work and social adjustment; sleep, menopause beliefs, HFNS beliefs/behaviors at 6 and 20 weeks; improved wellbeing and somatic symptoms and reduced work impairment due to menopause-related presenteeism at 20 weeks, compared with the NTWC. There was no difference between groups in other work-related outcomes. Conclusions: A brief, unguided SH-CBT booklet is a potentially effective management option for working women experiencing problematic HFNS.
Mindfulness-Based Stress Reduction vs Escitalopram for the Treatment of Adults With Anxiety Disorders: A Randomized Clinical Trial.
Importance: Anxiety disorders are common, highly distressing, and impairing conditions. Effective treatments exist, but many patients do not access or respond to them. Mindfulness-based interventions, such as mindfulness-based stress reduction (MBSR) are popular and can decrease anxiety, but it is unknown how they compare to standard first-line treatments. Objective: To determine whether MBSR is noninferior to escitalopram, a commonly used first-line psychopharmacological treatment for anxiety disorders. Design, setting, and participants: This randomized clinical trial (Treatments for Anxiety: Meditation and Escitalopram [TAME]) included a noninferiority design with a prespecified noninferiority margin. Patients were recruited between June 2018 and February 2020. The outcome assessments were performed by blinded clinical interviewer at baseline, week 8 end point, and follow-up visits at 12 and 24 weeks. Of 430 individuals assessed for inclusion, 276 adults with a diagnosed anxiety disorder from 3 urban academic medical centers in the US were recruited for the trial, and 208 completed the trial. Interventions: Participants were 1:1 randomized to 8 weeks of the weekly MBSR course or the antidepressant escitalopram, flexibly dosed from 10 to 20 mg. Main outcomes and measures: The primary outcome measure was anxiety levels as assessed with the Clinical Global Impression of Severity scale (CGI-S), with a predetermined noninferiority margin of -0.495 points. Results: The primary noninferiority sample consisted of 208 patients (102 in MBSR and 106 in escitalopram), with a mean (SD) age of 33 (13) years; 156 participants (75%) were female; 32 participants (15%) were African American, 41 (20%) were Asian, 18 (9%) were Hispanic/Latino, 122 (59%) were White, and 13 (6%) were of another race or ethnicity (including Native American or Alaska Native, more than one race, or other, consolidated owing to low numbers). Baseline mean (SD) CGI-S score was 4.44 (0.79) for the MBSR group and 4.51 (0.78) for the escitalopram group in the per-protocol sample and 4.49 (0.77) vs 4.54 (0.83), respectively, in the randomized sample. At end point, the mean (SD) CGI-S score was reduced by 1.35 (1.06) for MBSR and 1.43 (1.17) for escitalopram. The difference between groups was -0.07 (0.16; 95% CI, -0.38 to 0.23; P = .65), where the lower bound of the interval fell within the predefined noninferiority margin of -0.495, indicating noninferiority of MBSR compared with escitalopram. Secondary intent-to-treat analyses using imputed data also showed the noninferiority of MBSR compared with escitalopram based on the improvement in CGI-S score. Of patients who started treatment, 10 (8%) dropped out of the escitalopram group and none from the MBSR group due to adverse events. At least 1 study-related adverse event occurred for 110 participants randomized to escitalopram (78.6%) and 21 participants randomized to MBSR (15.4%). Conclusions and relevance: The results from this randomized clinical trial comparing a standardized evidence-based mindfulness-based intervention with pharmacotherapy for the treatment of anxiety disorders found that MBSR was noninferior to escitalopram. Trial registration: ClinicalTrials.gov Identifier: NCT03522844.
Cancer mortality in India: a nationally representative survey.
Background: The age-specific mortality rates and total deaths from specific cancers have not been documented for the various regions and subpopulations of India. We therefore assessed the cause of death in 2001-03 in homes in small areas that were chosen to be representative of all the parts of India. Methods: At least 130 trained physicians independently assigned causes to 122,429 deaths, which occurred in 1·1 million homes in 6671 small areas that were randomly selected to be representative of all of India, based on a structured non-medical surveyor's field report. Findings: 7137 of 122,429 study deaths were due to cancer, corresponding to 556,400 national cancer deaths in India in 2010. 395,400 (71%) cancer deaths occurred in people aged 30-69 years (200,100 men and 195,300 women). At 30-69 years, the three most common fatal cancers were oral (including lip and pharynx, 45,800 [22·9%]), stomach (25,200 [12·6%]), and lung (including trachea and larynx, 22,900 [11·4%]) in men, and cervical (33,400 [17·1%]), stomach (27,500 [14·1%]), and breast (19,900 [10·2%]) in women. Tobacco-related cancers represented 42·0% (84,000) of male and 18·3% (35,700) of female cancer deaths and there were twice as many deaths from oral cancers as lung cancers. Age-standardised cancer mortality rates per 100,000 were similar in rural (men 95·6 [99% CI 89·6-101·7] and women 96·6 [90·7-102·6]) and urban areas (men 102·4 [92·7-112·1] and women 91·2 [81·9-100·5]), but varied greatly between the states, and were two times higher in the least educated than in the most educated adults (men, illiterate 106·6 [97·4-115·7] vs most educated 45·7 [37·8-53·6]; women, illiterate 106·7 [99·9-113·6] vs most educated 43·4 [30·7-56·1]). Cervical cancer was far less common in Muslim than in Hindu women (study deaths 24, age-standardised mortality ratio 0·68 [0·64-0·71] vs 340, 1·06 [1·05-1·08]). Interpretation: Prevention of tobacco-related and cervical cancers and earlier detection of treatable cancers would reduce cancer deaths in India, particularly in the rural areas that are underserved by cancer services. The substantial variation in cancer rates in India suggests other risk factors or causative agents that remain to be discovered. Funding: Bill & Melinda Gates Foundation and US National Institutes of Health.
Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial.
Background: Obesity is associated with a reduction in life expectancy and an increase in mortality from cardiovascular diseases, cancer, and other causes. We therefore assessed the efficacy and safety of two doses of phentermine plus topiramate controlled-release combination as an adjunct to diet and lifestyle modification for weight loss and metabolic risk reduction in individuals who were overweight and obese, with two or more risk factors. Methods: In this 56-week phase 3 trial, we randomly assigned overweight or obese adults (aged 18-70 years), with a body-mass index of 27-45 kg/m(2) and two or more comorbidities (hypertension, dyslipidaemia, diabetes or prediabetes, or abdominal obesity) to placebo, once-daily phentermine 7·5 mg plus topiramate 46·0 mg, or once-daily phentermine 15·0 mg plus topiramate 92·0 mg in a 2:1:2 ratio in 93 centres in the USA. Drugs were administered orally. Patients were randomly assigned by use of a computer-generated algorithm that was implemented through an interactive voice response system, and were stratified by sex and diabetic status. Investigators, patients, and study sponsors were masked to treatment. Primary endpoints were the percentage change in bodyweight and the proportion of patients achieving at least 5% weight loss. Analysis was by intention to treat. This study is registered with Clinical Trials.gov, number NCT00553787. Findings: Of 2487 patients, 994 were assigned to placebo, 498 to phentermine 7·5 mg plus topiramate 46·0 mg, and 995 to phentermine 15·0 mg plus topiramate 92·0 mg; 979, 488, and 981 patients, respectively, were analysed. At 56 weeks, change in bodyweight was -1·4 kg (least-squares mean -1·2%, 95% CI -1·8 to -0·7), -8·1 kg (-7·8%, -8·5 to -7·1; p<0·0001), and -10·2 kg (-9·8%, -10·4 to -9·3; p<0·0001) in the patients assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus topiramate 92·0 mg, respectively. 204 (21%) patients achieved at least 5% weight loss with placebo, 303 (62%; odds ratio 6·3, 95% CI 4·9 to 8·0; p<0·0001) with phentermine 7·5 mg plus topiramate 46·0 mg, and 687 (70%; 9·0, 7·3 to 11·1; p<0·0001) with phentermine 15·0 mg plus topiramate 92·0 mg; for ≥10% weight loss, the corresponding numbers were 72 (7%), 182 (37%; 7·6, 5·6 to 10·2; p<0·0001), and 467 (48%; 11·7, 8·9 to 15·4; p<0·0001). The most common adverse events were dry mouth (24 [2%], 67 [13%], and 207 [21%] in the groups assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus topiramate 92·0 mg, respectively), paraesthesia (20 [2%], 68 [14%], and 204 [21%], respectively), constipation (59 [6%], 75 [15%], and 173 [17%], respectively), insomnia (47 [5%], 29 [6%], and 102 [10%], respectively), dizziness (31 [3%], 36 [7%], 99 [10%], respectively), and dysgeusia (11 [1%], 37 [7%], and 103 [10%], respectively). 38 (4%) patients assigned to placebo, 19 (4%) to phentermine 7·5 mg plus topiramate 46·0 mg, and 73 (7%) to phentermine 15·0 mg plus topiramate 92·0 mg had depression-related adverse events; and 28 (3%), 24 (5%), and 77 (8%), respectively, had anxiety-related adverse events. Interpretation: The combination of phentermine and topiramate, with office-based lifestyle interventions, might be a valuable treatment for obesity that can be provided by family doctors. Funding: Vivus.
Adjuvant chemotherapy with cisplatin and gemcitabine versus chemotherapy at relapse in patients with muscle-invasive bladder cancer submitted to radical cystectomy: an Italian, multicenter, randomized phase III trial.
Background: The purpose of the study was to evaluate the benefit of adjuvant chemotherapy (AC) versus surgery alone in patients with muscle-invasive bladder cancer (MIBC). Patients and methods: One hundred and ninety-four patients with pT2G3, pT3-4, N0-2 transitional cell bladder carcinoma were randomly allocated to control (92 patients) or to four courses of AC (102 patients). These latter patients were further randomly assigned to receive gemcitabine 1000 mg/m(2) days 1, 8 and 15 and cisplatin 70 mg/m(2) day 2 or gemcitabine as above plus cisplatin 70 mg/m(2) day 15, every 28 days. Results: At a median follow-up of 35 months, the 5-year overall survival (OS) was 48.5%, with no difference between the two arms [P = 0.24, hazard ratio (HR) 1.29, 95% confidence interval (CI) 0.84-1.99]. Mortality hazard was significantly correlated with Nodes (N) and Tumor (T) stage. The control and AC arms had comparable disease-free survival (42.3% and 37.2%, respectively; P = 0.70, HR 1.08, 95% CI 0.73-1.59). Only 62% of patients received the planned cycles. A significant higher incidence of thrombocytopenia was observed in patients receiving cisplatin on day 2 (P = 0.006). A similar global quality of life was observed in the two arms. Conclusion: The study was underpowered to demonstrate that AC with cisplatin and gemcitabine improves OS and disease-free survival in patients with MIBC.
Herbal treatments for alleviating premenstrual symptoms: a systematic review.
Premenstrual syndrome (PMS) is a condition of cyclical and recurrent physical and psychological discomfort occurring 1 to 2 weeks before menstrual period. More severe psychological symptoms have been described for the premenstrual dysphoric disorder (PMDD). No single treatment is universally recognised as effective and many patients often turn to therapeutic approaches outside of conventional medicine. This systematic review is aimed at analysing the effects of herb remedies in the above conditions. Systematic literature searches were performed in electronic databases, covering the period January 1980 to September 2010. Randomised controlled clinical trials (RCTs) were included. Papers quality was evaluated with the Jadad' scale. A further evaluation of PMS/PMDD diagnostic criteria was also done. Of 102 articles identified, 17 RCTs were eligible and 10 of them were included. The heterogeneity of population included, study design and outcome presentation refrained from a meta-analysis. Vitex agnus castus was the more investigated remedy (four trials, about 500 women), and it was reported to consistently ameliorate PMS better than placebo. Single trials also support the use of either Gingko biloba or Crocus sativus. On the contrary, neither evening primrose oil nor St. John's Wort show an effect different than placebo. None of the herbs was associated with major health risks, although the reduced number of tested patients does not allow definitive conclusions on safety. Some herb remedies seem useful for the treatment of PMS. However, more RCTs are required to account for the heterogeneity of the syndrome.
Effect of immunotherapy time-of-day infusion on overall survival among patients with advanced melanoma in the USA (MEMOIR): a propensity score-matched analysis of a single-centre, longitudinal study.
Background: The dependence of the adaptive immune system on circadian rhythm is an emerging field of study with potential therapeutic implications. We aimed to determine whether specific time-of-day patterns of immune checkpoint inhibitor infusions might alter melanoma treatment efficacy. Methods: Melanoma Outcomes Following Immunotherapy (MEMOIR) is a longitudinal study of all patients with melanoma who received ipilimumab, nivolumab, or pembrolizumab, or a combination of these at a single tertiary cancer centre (Winship Cancer Institute of Emory University, Atlanta, GA, USA). For this analysis, we collected deidentified participant-level data from the MEMOIR database for adults (age ≥18 years) diagnosed with stage IV melanoma between 2012 and 2020. Those who received fewer than four infusions were excluded. Standard of care doses were used, with modifications at the treating physicians' discretion. The primary outcome was overall survival, defined as death from any cause and indexed from date of first infusion of immune checkpoint inhibitor. We calculated the association between overall survival and proportion of infusions of immune checkpoint inhibitors received after 1630 h (a composite time cutoff derived from seminal studies of the immune-circadian rhythm to represent onset of evening) using Cox regression and propensity score-matching on age, Eastern Cooperative Oncology Group performance status, serum lactate dehydrogenase concentration, and receipt of corticosteroids and radiotherapy. Treatment-related adverse events that led to change or discontinuation of immune checkpoint inhibitors were also assessed. Findings: Between Jan 1, 2012, and Dec 31, 2020, 481 patients with melanoma received treatment with immune checkpoint inhibitors at the study centre, of whom 299 had stage IV disease and were included in this study; median follow-up was 27 months (IQR 14 to 47). In the complete unmatched sample, 102 (34%) patients were female and 197 (66%) were male, with a median age of 61 years (IQR 51 to 72). Every additional 20% of infusions of immune checkpoint inhibitors received after 1630 h (among all infusions received by a patient) conferred an overall survival hazard ratio (HR) of 1·31 (95% CI 1·00 to 1·71; p=0·046). A propensity score-matched analysis of patients who did (n=73) and did not (n=73) receive at least 20% of their infusions of immune checkpoint inhibitors after 1630 h (54 [37%] of 146 patients were women and 92 [63%] were men, with a median age of 58 years [IQR 48 to 68]) showed that having at least 20% of infusions in the evening was associated with shorter overall survival (median 4·8 years [95% CI 3·9 to not estimable] vs not reached; HR 2·04 [1·04 to 4·00; p=0·038]). This result remained robust to multivariable proportional hazards adjustment with (HR 1·80 [1·08 to 2·98; p=0·023]) and without (2·16 [1·10 to 4·25; p=0·025]) inclusion of the complete unmatched study sample. The most common adverse events were colitis (54 [18%] of 299 patients), hepatitis (27 [9%]), and hypophysitis (15 [5%]), and there were no treatment-related deaths. Interpretation: Our findings are in line with an increasing body of evidence that adaptive immune responses are less robust when initially stimulated in the evening than if stimulated in the daytime. Although prospective studies of the timing of immune checkpoint inhibitor infusions are warranted, efforts towards scheduling infusions before mid-afternoon could be considered in the multidisciplinary management of advanced melanoma. Funding: National Institutes of Health, American Society for Radiation Oncology and Melanoma Research Alliance, and Winship Cancer Institute.
Changes in cognitive function in a randomized trial of physical activity: results of the lifestyle interventions and independence for elders pilot study.
Background: Cognitive impairment is an important contributor to disability. Limited clinical trial evidence exists regarding the impact of physical exercise on cognitive function (CF). We report results of a pilot study to provide estimates of the relative impact of physical activity (PA) on 1-year changes in cognitive outcomes and to characterize relationships between changes in mobility disability and changes in cognition in older adults at increased risk for disability. Methods: Sedentary persons (102) at increased risk for disability (aged 70-89 years) were randomized to moderate-intensity PA or health education. Participants were administered the Digit Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test (RAVLT), modified Stroop test, and Modified Mini-Mental State Examination at baseline and 1 year. Results: Group differences were not significant but improvements in cognitive scores were associated with improvements in physical function. Specifically, the DSST significantly correlated with change in the Short Physical Performance Battery score (r = .38, p = .0002), in chair stand score (r = .26, p = .012), in balance score (r = .21, p = .046), and in 400-m gait speed (r = .15, p = .147). Change recall on the RAVLT and in the Stroop test was also positively correlated with changes in chair stand and balance, respectively. Conclusions: These results provide further support for the benefits of exercise on CF in older adults. An adequately powered clinical trial of PA involving older adults at increased risk for cognitive disability is needed to expand the indications for prescribing exercise for prevention of decline in brain function.
Efficacy of REACH Forgiveness across cultures.
Objective: This study investigates the efficacy of the 6-hour REACH Forgiveness intervention among culturally diverse undergraduates. Method: Female undergraduates (N = 102) and foreign extraction (46.2%) and domestic (43.8%) students in the United States were randomly assigned to immediate treatment or waitlist conditions. Treatment efficacy and the effect of culture on treatment response were assessed using measures of emotional and decisional forgiveness across 3 time periods. Results: Students in the treatment condition reported greater improvement in emotional forgiveness, but not decisional forgiveness, relative to those in the waitlist condition. Gains were maintained at a 1-week follow-up. Although culture did not moderate the effect of treatment, a main effect of culture on emotional forgiveness and marginally significant interaction effect of culture on decisional forgiveness were found. Conclusion: The REACH Forgiveness intervention was efficacious for college students from different cultural backgrounds when conducted in the United States. However, some evidence may warrant development of culturally adapted forgiveness interventions.
Treatment outcomes of a stage 1 cognitive-behavioral trial to reduce alcohol use among human immunodeficiency virus-infected out-patients in western Kenya.
Aims: Dual epidemics of human immunodeficiency virus (HIV) and alcohol use disorders, and a dearth of professional resources for behavioral treatment in sub-Saharan Africa, suggest the need for development of culturally relevant and feasible interventions. The purpose of this study was to test the preliminary efficacy of a culturally adapted six-session gender-stratified group cognitive-behavioral therapy (CBT) intervention delivered by paraprofessionals to reduce alcohol use among HIV-infected out-patients in Eldoret, Kenya. Design: Randomized clinical trial comparing CBT against a usual care assessment-only control. Setting: A large HIV out-patient clinic in Eldoret, Kenya, part of the Academic Model for Providing Access to Healthcare collaboration. Participants: Seventy-five HIV-infected out-patients who were antiretroviral (ARV)-initiated or ARV-eligible and who reported hazardous or binge drinking. Measurements: Percentage of drinking days (PDD) and mean drinks per drinking days (DDD) measured continuously using the Time line Follow back method. Findings: There were 299 ineligible and 102 eligible out-patients with 12 refusals. Effect sizes of the change in alcohol use since baseline between the two conditions at the 30-day follow-up were large [d=0.95, P=0.0002, mean difference=24.93, 95% confidence interval (CI): 12.43, 37.43 PDD; d=0.76, P=0.002, mean difference=2.88, 95% CI: 1.05, 4.70 DDD]. Randomized participants attended 93% of the six CBT sessions offered. Reported alcohol abstinence at the 90-day follow-up was 69% (CBT) and 38% (usual care). Paraprofessional counselors achieved independent ratings of adherence and competence equivalent to college-educated therapists in the United States. Treatment effect sizes were comparable to alcohol intervention studies conducted in the United States. Conclusions: Cognitive-behavioral therapy can be adapted successfully to group paraprofessional delivery in Kenya and may be effective in reducing alcohol use among HIV-infected Kenyan out-patients.
Melatonin agonist tasimelteon (VEC-162) for transient insomnia after sleep-time shift: two randomised controlled multicentre trials.
Background: Circadian rhythm sleep disorders are common causes of insomnia for millions of individuals. We did a phase II study to establish efficacy and physiological mechanism, and a phase III study to confirm efficacy of the melatonin agonist tasimelteon (VEC-162) for treatment of transient insomnia associated with shifted sleep and wake time. Methods: We undertook phase II and phase III randomised, double-blind, placebo-controlled, parallel-group studies. In a phase II study, 39 healthy individuals from two US sites were randomly assigned to tasimelteon (10 [n=9], 20 [n=8], 50 [n=7], or 100 mg [n=7]) or placebo (n=8). We monitored individuals for 7 nights: 3 at baseline, 3 after a 5-h advance of sleep-wake schedule with treatment before sleep, and 1 after treatment; we measured plasma melatonin concentration for circadian phase assessment. In a phase III study, 411 healthy individuals from 19 US sites, who had transient insomnia induced in a sleep clinic by a 5-h advance of the sleep-wake schedule and a first-night effect in a sleep clinic, were given tasimelteon (20 [n=100], 50 [n=102], or 100 mg [n=106]) or placebo (n=103) 30 min before bedtime. Prespecified primary efficacy outcomes were polysomnographic sleep efficiency (phase II study), latency to persistent sleep (phase III study), and circadian phase shifting (phase II study). Analysis was by intention to treat. Safety was assessed in both studies. These trials are registered with ClinicalTrials.gov, numbers NCT00490945 and NCT00291187. Findings: In the phase II study, tasimelteon reduced sleep latency and increased sleep efficiency compared with placebo. The shift in plasma melatonin rhythm to an earlier hour was dose dependent. In the phase III study, tasimelteon improved sleep latency, sleep efficiency, and wake after sleep onset (ie, sleep maintenance). The frequency of adverse events was similar between tasimelteon and placebo. Interpretation: After an abrupt advance in sleep time, tasimelteon improved sleep initiation and maintenance concurrently with a shift in endogenous circadian rhythms. Tasimelteon may have therapeutic potential for transient insomnia in circadian rhythm sleep disorders.
Exergaming and older adult cognition: a cluster randomized clinical trial.
Background: Dementia cases may reach 100 million by 2050. Interventions are sought to curb or prevent cognitive decline. Exercise yields cognitive benefits, but few older adults exercise. Virtual reality-enhanced exercise or "exergames" may elicit greater participation. Purpose: To test the following hypotheses: (1) stationary cycling with virtual reality tours ("cybercycle") will enhance executive function and clinical status more than traditional exercise; (2) exercise effort will explain improvement; and (3) brain-derived neurotrophic growth factor (BDNF) will increase. Design: Multi-site cluster randomized clinical trial (RCT) of the impact of 3 months of cybercycling versus traditional exercise, on cognitive function in older adults. Data were collected in 2008-2010; analyses were conducted in 2010-2011. Setting/participants: 102 older adults from eight retirement communities enrolled; 79 were randomized and 63 completed. Interventions: A recumbent stationary ergometer was utilized; virtual reality tours and competitors were enabled on the cybercycle. Main outcome measures: Executive function (Color Trails Difference, Stroop C, Digits Backward); clinical status (mild cognitive impairment; MCI); exercise effort/fitness; and plasma BDNF. Results: Intent-to-treat analyses, controlling for age, education, and cluster randomization, revealed a significant group X time interaction for composite executive function (p=0.002). Cybercycling yielded a medium effect over traditional exercise (d=0.50). Cybercyclists had a 23% relative risk reduction in clinical progression to MCI. Exercise effort and fitness were comparable, suggesting another underlying mechanism. A significant group X time interaction for BDNF (p=0.05) indicated enhanced neuroplasticity among cybercyclists. Conclusions: Cybercycling older adults achieved better cognitive function than traditional exercisers, for the same effort, suggesting that simultaneous cognitive and physical exercise has greater potential for preventing cognitive decline. Trial registration: This study is registered at Clinicaltrials.gov NCT01167400.
Pilot data of a brief veteran peer intervention and its relationship to mental health treatment engagement.
Underutilization of mental health care is a significant problem among veterans. Offering peer support may improve mental health care engagement. This observational pilot study was conducted using an institutional review board-approved data repository to preliminarily evaluate the association and potential impact of a clinic-based veteran peer outreach strategy on treatment engagement and dropout. Veteran peer outreach coordinators (VPOCs) provided systematic contact (a) within 1 week after clinical evaluation and (b) 1 month after the patient's first treatment session to patients entering treatment at a specialty mental health clinic that provides military-informed mental health care to post-9/11 veterans and service members. Individuals were 102 consecutive Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn veteran psychotherapy referrals seen at an outpatient clinic. At 6 months, participants who received both contacts from VPOC had more psychotherapy sessions (M = 10.85, SD = 8.25) compared with those who had received no contact (M = 5.47, SD = 6.41) from VPOCs, t = 2.56, p < .05. The dropout rate was also significantly lower for those who received both peer outreach contacts (17.39%) compared with those who received only 1 VPOC contact (51.11%) or no VPOC contact (43.75%), χ2 = 7.27, p < .05. Veteran peer outreach may be associated with better engagement in mental health treatment and lower dropout. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
The epidemiology of trauma and post-traumatic stress disorder in a representative cohort of young people in England and Wales.
Background: Despite the emphasis placed on childhood trauma in psychiatry, comparatively little is known about the epidemiology of trauma and trauma-related psychopathology in young people. We therefore aimed to evaluate the prevalence, clinical features, and risk factors associated with trauma exposure and post-traumatic stress disorder (PTSD) in young people. Methods: We carried out a comprehensive epidemiological study based on participants from the Environmental Risk Longitudinal Twin Study, a population-representative birth-cohort of 2232 children born in England and Wales in 1994-95. At the follow-up home visit at age 18 years, participants were assessed with structured interviews for trauma exposure, PTSD, other psychopathology, risk events, functional impairment, and service use. Risk factors for PTSD were measured prospectively over four previous assessments between age 5 and 12 years. The key outcomes were the prevalence, clinical features, and risk factors associated with trauma exposure and PTSD. We also derived and tested the internal validity of a PTSD risk calculator. Findings: We found that 642 (31·1%) of 2064 participants reported trauma exposure and 160 (7·8%) of 2063 experienced PTSD by age 18 years. Trauma-exposed participants had high rates of psychopathology (187 [29·2%] of 641 for major depressive episode, 146 [22·9%] of 638 for conduct disorder, and 102 [15·9%] of 641 for alcohol dependence), risk events (160 [25·0%] of 641 for self-harm, 53 [8·3%] of 640 for suicide attempt, and 42 [6·6%] of 640 for violent offence), and functional impairment. Participants with lifetime PTSD had even higher rates of psychopathology (87 [54·7%] of 159 for major depressive episode, 43 [27·0%] of 159 for conduct disorder, and 41 [25·6%] of 160 for alcohol dependence), risk events (78 [48·8%] of 160 for self-harm, 32 [20·1%] of 159 for suicide attempt, and 19 [11·9%] of 159 for violent offence), and functional impairment. However, only 33 (20·6%) of 160 participants with PTSD received help from mental health professionals. The PTSD risk calculator had an internally validated area under the receiver operating characteristic curve of 0·74, indicating adequate discrimination of trauma-exposed participants with and without PTSD, and internally validated calibration-in-the-large of -0·10 and calibration slope of 0·90, indicating adequate calibration. Interpretation: Trauma exposure and PTSD are associated with complex psychiatric presentations, high risk, and significant impairment in young people. Improved screening, reduced barriers to care provision, and comprehensive clinical assessment are needed to ensure that trauma-exposed young people and those with PTSD receive appropriate treatment. Funding: The Medical Research Council, the National Institute of Child Health and Development, the Jacobs Foundation, the Nuffield Foundation, the National Society for Prevention of Cruelty to Children, the Economic and Social Research Council, the National Institute for Health Research, MQ, and Canadian Institutes for Advanced Research.
Development and Validation of the Self-Compassion Scale for Youth.
We present a series of studies on the development and validation of the Self-Compassion Scale-Youth version (SCS-Y), which is intended for use with early adolescents in middle school. Study 1 (N = 279, Mage = 12.17) describes the selection of 17 items out of a pool of 36 potential items, with three items each representing the subscales of self-kindness, mindfulness, common humanity, self-judgment, isolation, and two items representing over-identification. Using state-of-the-art psychometric analyses ideal for examining multidimensional constructs like self-compassion-bifactor exploratory structural equation modeling (bifactor-ESEM)-findings supported the use of a general self-compassion score and six subscale scores. Study 2 cross-validated the factor structure of the SCS-Y with a second sample of youths (N = 402, Mage = 12.43). Study 3 found support for the test-retest reliability of the SCS-Y (N = 102, Mage = 12.52). Study 4 (N = 212, Mage = 12.18) established construct validity for the SCS-Y by demonstrating that SCS-Y scores were significantly associated with mindfulness, happiness, life-satisfaction, depression, resilience, and achievement goal orientation in expected directions. Overall, findings suggest that the SCS-Y is a reliable and valid measure of self-compassion for use with youths.
The Effectiveness of Family Constellation Therapy in Reducing Psychopathological Symptoms in a Naturalistic Setting.
Background: The aim of this study (ClinicalTrials.gov identifier: NCT03233958) was to provide further evidence on the effectiveness and safety of family/systemic constellation therapy, a widely used but rarely investigated form of brief group psychotherapy. Subjects and methods: Altogether, 102 individuals from the general population were followed up 1- and 6 months after their participation in the 2-day intervention. Indicators of general and problem-area-specific psychopathology, interpersonal quality of life, meaning in life, and general wellbeing were assessed. Both statistical and clinical significance were considered, and active surveillance of potential iatrogenic effects was also conducted. Results: The data showed significant improvement post-intervention in the case of the vast majority of the 17 outcome variables. At 1-month follow-up, the magnitude of improvements was typically in the moderate range. The patterns were very similar at the 6-month follow-up, suggesting that most intervention benefits were sustained in the middle term. Sensitivity analyses showed no therapist effects across the three intervention providers. Analyses into clinical significance showed that the most reliable improvements occurred in relation to interpersonal quality of life and non-diagnosis-specific psychopathology, with approximately half of the participants showing reliable improvement. Iatrogenic effects were comparable - both in terms of frequency and severity - to those reported for other forms of psychotherapy. Conclusions: Findings of the present study point toward the safety and effectiveness of family constellation therapy in reducing a variety of psychopathological symptoms (e.g., depression and anxiety) and increasing general well-being. This effectiveness is especially remarkable when considering the brevity and cost-effectiveness of the intervention.
Subjective and Objective Measurement of Sleep Quality and Activity in Glaucoma.
Prcis: Glaucoma patients exhibit worse indices of sleep function by both objective and subjective metrics compared with controls. Purpose: The purpose of this study is to characterize the sleep parameters and physical activity levels of glaucoma patients compared with controls. Patients and methods: A total of 102 patients with a diagnosis of glaucoma in at least 1 eye and 31 control subjects were enrolled in the study. Participants completed the Pittsburgh Sleep Quality Index (PSQI) during enrollment and then wore wrist actigraphs for 7 consecutive days to characterize circadian rhythm, sleep quality, and physical activity. The primary outcomes of the study were subjective and objective metrics of sleep quality using the PSQI and actigraphy devices, respectively. The secondary outcome was physical activity, measured by the actigraphy device. Results: From the PSQI survey, glaucoma patients had higher (worse) scores compared with controls for sleep latency, sleep duration, and subjective sleep quality, whereas scores for sleep efficiency were lower (better), suggesting more time spent in bed asleep. By actigraphy, time in bed was significantly higher in glaucoma patients as was time awake after sleep onset. Interdaily stability, quantifying the synchronization to the 24-hour light-dark cycle, was lower in glaucoma patients. There were no other significant differences between glaucoma and control patients with regard to rest-activity rhythms or physical activity metrics. In contrast to the survey data, findings from the actigraphy demonstrated that there were no significant associations between the study group and controls regarding sleep efficiency, onset latency, or total sleep time. Conclusions: In this study, patients with glaucoma demonstrated several subjective and objective differences in sleep function when compared with controls, whereas physical activity metrics were similar.
Findings of a Pilot Study Investigating the Effects of Mediterranean Diet and Aerobic Exercise on Cognition in Cognitively Healthy Older People Living Independently within Aged-Care Facilities: The Lifestyle Intervention in Independent Living Aged Care (LIILAC) Study.
Background: Cognitive decline and Alzheimer disease are more prevalent in our aging population. Modifiable risk factors, such as diet and sedentary lifestyle, have been proposed as key to potentially ameliorating cognitive decline. Both exercise and Mediterranean diet (MedDiet) have been linked to reduced levels of cardiovascular disease and other comorbidities. Higher levels of exercise and MedDiet adherence may prove to be cognitively protective, both individually and synergistically. Objectives: The aim was to investigate the effect of a 6-mo program of MedDiet, exercise, and a combination of both, on cognition, mood, and general health in older persons living independently in aged-care communities. Methods: The Lifestyle Intervention in Independent Living Aged Care (LIILAC) Study (ACTRN12614001133628) involved 102 participants, aged 60-90 y, who were randomly assigned to 1 of 4 intervention groups. Change in overall memory performance was assessed as the primary outcome. Additionally, changes in cognitive task performance, as well as mood, wellness, cardiovascular function, and blood biomarkers, were investigated. Results: While there was no significant change in overall memory performance, there was a significant improvement in spatial working memory performance in the combined exercise and diet group, relative to controls. This combined intervention group also showed an overall improvement in their emotional state, as assessed by the Depression Anxiety Stress Scale, as did the exercise-only group. Conclusions: This research indicates that diet and exercise programs have the potential to improve aspects of cognition and mood in an aging population. However, given the lower than optimal sample size and lack of resources to reinforce the interventions during the trial, further larger randomized controlled trials are required to substantiate whether the introduction of diet and exercise programs into independent-living facilities is a viable method to preserve cognitive health in older people. This trial was registered at www.ANZCTR.org.au ACTRN 12614001133628 (LIILAC Study).
A rapid synthesis of the evidence on interventions supporting self-management for people with long-term conditions: PRISMS – Practical systematic Review of Self-Management Support for long-term conditions
Background: Despite robust evidence concerning self-management for some long-term conditions (LTCs), others lack research explicitly on self-management and, consequently, some patient groups may be overlooked. Aim: To undertake a rapid, systematic overview of the evidence on self-management support for LTCs to inform health-care commissioners and providers about what works, for whom, and in what contexts. Methods: Self-management is ‘the tasks . . . individuals must undertake to live with one or more chronic conditions . . . [including] . . . having the confidence to deal with medical management, role management and emotional management of their conditions’. We convened an expert workshop and identified characteristics of LTCs potentially of relevance to self-management and 14 diverse exemplar LTCs (stroke, asthma, type 2 diabetes mellitus, depression, chronic obstructive pulmonary disease, chronic kidney disease, dementia, epilepsy, hypertension, inflammatory arthropathies, irritable bowel syndrome, low back pain, progressive neurological disorders and type 1 diabetes mellitus). For each LTC we conducted systematic overviews of systematic reviews of randomised controlled trials (RCTs) of self-management support interventions (‘quantitative meta-reviews’); and systematic overviews of systematic reviews of qualitative studies of patients’ experiences relating to self-management (‘qualitative meta-reviews’). We also conducted an original systematic review of implementation studies of self-management support in the LTCs. We synthesised all our data considering the different characteristics of LTCs. In parallel, we developed a taxonomy of the potential components of self-management support. Results: We included 30 qualitative systematic reviews (including 515 unique studies), 102 quantitative systematic reviews (including 969 RCTs), and 61 studies in the implementation systematic review. Effective self-management support interventions are multifaceted, should be tailored to the individual, their culture and beliefs, a specific LTC and position on the disease trajectory, and underpinned by a collaborative/communicative relationship between the patient and health-care professional (HCP) within the context of a health-care organisation that actively promotes self-management. Self-management support is a complex intervention and although many components were described and trialled in the studies no single component stood out as more important than any other. Core components include (1) provision of education about the LTC, recognising the importance of understanding patients’ pre-existing knowledge and beliefs about their LTC; (2) psychological strategies to support adjustment to life with a LTC; (3) strategies specifically to support adherence to treatments; (4) practical support tailored to the specific LTC, including support around activities of daily living for disabling conditions, action plans in conditions subject to marked exacerbations, intensive disease-specific training to enable self-management of specific clinical tasks; and (5) social support as appropriate. Implementation requires a whole-systems approach which intervenes at the level of the patient, the HCP and the organisation. The health-care organisation is responsible for providing the means (both training and time/material resources) to enable HCPs to implement, and patients to benefit from, self-management support, regularly evaluating self-management processes and clinical outcomes. More widely there is a societal need to address public understanding of LTCs. The lack of public story for many conditions impacted on patient help-seeking behaviour and public perceptions of need. Conclusions: Supporting self-management is inseparable from the high-quality care for LTCs. Commissioners and health-care providers should promote a culture of actively supporting self-management as a normal, expected, monitored and rewarded aspect of care. Further research is needed to understand how health service managers and staff can achieve this culture change in their health-care organisations. Study registration: This study is registered as PROSPERO CRD42012002898. Funding: The National Institute for Health Research Health Services and Delivery Research programme.
Obstetric Care Consensus #10: Management of Stillbirth: (Replaces Practice Bulletin Number 102, March 2009).
Stillbirth is one of the most common adverse pregnancy outcomes, occurring in 1 in 160 deliveries in the United States. In developed countries, the most prevalent risk factors associated with stillbirth are non-Hispanic black race, nulliparity, advanced maternal age, obesity, preexisting diabetes, chronic hypertension, smoking, alcohol use, having a pregnancy using assisted reproductive technology, multiple gestation, male fetal sex, unmarried status, and past obstetric history. Although some of these factors may be modifiable (such as smoking), many are not. The study of specific causes of stillbirth has been hampered by the lack of uniform protocols to evaluate and classify stillbirths and by decreasing autopsy rates. In any specific case, it may be difficult to assign a definite cause to a stillbirth. A significant proportion of stillbirths remains unexplained, even after a thorough evaluation. Evaluation of a stillbirth should include fetal autopsy; gross and histologic examination of the placenta, umbilical cord, and membranes; and genetic evaluation. The method and timing of delivery after a stillbirth depend on the gestational age at which the death occurred, maternal obstetric history (eg, previous hysterotomy), and maternal preference. Health care providers should weigh the risks and benefits of each strategy in a given clinical scenario and consider available institutional expertise. Patient support should include emotional support and clear communication of test results. Referral to a bereavement counselor, peer support group, or mental health professional may be advisable for management of grief and depression.
Touch as an Interpersonal Emotion Regulation Process in Couples’ Daily Lives
Interpersonal touch seems to promote physical health through its effects on stress-sensitive parameters. However, less is known about the psychological effects of touch. The present study investigates associations between touch and romantic partners' affective state in daily life. We hypothesized that this association is established by promoting the recipient's experience of intimacy. Both partners of 102 dating couples completed an electronic diary 4 times a day during 1 week. Multilevel analyses revealed that touch was associated with enhanced affect in the partner. This association was mediated by the partner's psychological intimacy. Touch was also associated with intimacy and positive affect in the actor. Finally, participants who were touched more often during the diary study week reported better psychological well-being 6 months later. This study provides evidence that intimate partners benefit from touch on a psychological level, conveying a sense of strengthened bonds between them that enhances affect and well-being.
Development of the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) gastrointestinal symptom scales.
Objectives: The National Institutes of Health (NIH) Patient-Reported Outcomes Measurement Information System (PROMIS(®)) is a standardized set of patient-reported outcomes (PROs) that cover physical, mental, and social health. The aim of this study was to develop the NIH PROMIS gastrointestinal (GI) symptom measures. Methods: We first conducted a systematic literature review to develop a broad conceptual model of GI symptoms. We complemented the review with 12 focus groups including 102 GI patients. We developed PROMIS items based on the literature and input from the focus groups followed by cognitive debriefing in 28 patients. We administered the items to diverse GI patients (irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), systemic sclerosis (SSc), and other common GI disorders) and a census-based US general population (GP) control sample. We created scales based on confirmatory factor analyses and item response theory modeling, and evaluated the scales for reliability and validity. Results: A total of 102 items were developed and administered to 865 patients with GI conditions and 1,177 GP participants. Factor analyses provided support for eight scales: gastroesophageal reflux (13 items), disrupted swallowing (7 items), diarrhea (5 items), bowel incontinence/soilage (4 items), nausea and vomiting (4 items), constipation (9 items), belly pain (6 items), and gas/bloat/flatulence (12 items). The scales correlated significantly with both generic and disease-targeted legacy instruments, and demonstrate evidence of reliability. Conclusions: Using the NIH PROMIS framework, we developed eight GI symptom scales that can now be used for clinical care and research across the full range of GI disorders.
Predicting the duration of sickness absence for patients with common mental disorders in occupational health care.
Objectives: This study attempted to determine the factors that best predict the duration of absence from work among employees with common mental disorders. Methods: A cohort of 188 employees, of whom 102 were teachers, on sick leave with common mental disorders was followed for 1 year. Only information potentially available to the occupational physician during a first consultation was included in the predictive model. The predictive power of the variables was tested using Cox's regression analysis with a stepwise backward selection procedure. The hazard ratios (HR) from the final model were used to deduce a simple prediction rule. The resulting prognostic scores were then used to predict the probability of not returning to work after 3, 6, and 12 months. Calculating the area under the curve from the ROC (receiver operating characteristic) curve tested the discriminative ability of the prediction rule. Results: The final Cox's regression model produced the following four predictors of a longer time until return to work: age older than 50 years [HR 0.5, 95% confidence interval (95% CI) 0.3-0.8], expectation of duration absence longer than 3 months (HR 0.5, 95% CI 0.3-0.8), higher educational level (HR 0.5, 95% CI 0.3-0.8), and diagnosis depression or anxiety disorder (HR 0.7, 95% CI 0.4-0.9). The resulting prognostic score yielded areas under the curves ranging from 0.68 to 0.73, which represent acceptable discrimination of the rule. Conclusions: A prediction rule based on four simple variables can be used by occupational physicians to identify unfavorable cases and to predict the duration of sickness absence.
The use of reflective journaling as a learning strategy during the clinical rotations of students from the faculty of health sciences: An action-research study.
Background: Reflective practice contributes significantly to the assimilation of knowledge in undergraduate health students. Reflective journals constitute a learning strategy that promotes student reflection during clinical practice. Aims: The overall aim of the study was to explore teachers' perceptions and experiences regarding the use of reflective clinical journals as a learning tool for students in order to improve the implementation of clinical journal writing in all the Health Science degrees offered by our University. Method: A qualitative research study was performed using the Action-Research method. Students studying various degrees at our Health Faculty were considered for this study (Nursing Physiotherapy, and Physiotherapy and Physical Activity and Sport Science). Data were collected using triangulation of document analysis (102 student journals and 12 teacher journals, together with the teachers' responses to the student's journals) and transcripts from 2 discussion groups (1 student discussion group and 1 teacher discussion group). Data analysis was performed based on the constant comparative method using ATLAS.ti version 6.2 software. Results: Four qualitative themes emerged from the data: the journal as a teaching strategy; building a relationship of trust between the tutor and the student; the role of the teacher and the world of emotions. Conclusions: Several recommendations for supporting clinical journal writing were identified: an informative meeting should be arranged with students; written guidelines should be provided; a personal interview with the student is recommended at the start of the activity; feedback should be offered over short time periods; teachers should provide constructive feedback; and students should adopt a free writing approach, or be guided by very open questions. Finally, it is important that students be familiarized with the assessment criteria.
Inhibition of Lipolysis Ameliorates Diabetic Phenotype in a Mouse Model of Obstructive Sleep Apnea.
Obstructive sleep apnea (OSA) is associated with insulin resistance, glucose intolerance, and type 2 diabetes. Causal mechanisms mediating this association are not well defined; however, augmented lipolysis in adipose might be involved. Here, we investigated the effect of acipimox treatment (lipolysis inhibitor) on glucose tolerance and insulin sensitivity in mice exposed to intermittent hypoxia (IH). C57BL6/J mice were exposed for 14 days to IH or control conditions. IH was created by decreasing the fraction of inspired oxygen from 20.9 to 6.5%, 60 times/h. Control exposure was air (fraction of inspired oxygen, 20.9%) delivered at an identical flow rate. Acipimox was provided in drinking water (0.5 g/ml) during exposures. After exposures, intraperitoneal insulin (0.5 IU/kg) and glucose (1 g/kg) tolerance tests were performed, and primary adipocytes were isolated for lipolysis experiments. IH elevated fasting glucose by 51% and worsened glucose tolerance and insulin sensitivity by 33 and 102%, respectively. In parallel, IH increased spontaneous lipolysis by 264%, and reduced epididymal fat mass by 15% and adipocyte size by 8%. Acipimox treatment prevented IH-induced lipolysis and increased epididymal fat mass and adipocyte size by 19 and 10%, respectively. Acipimox fully prevented IH-induced impairments in fasting glycemia, glucose tolerance, and insulin sensitivity. For all reported results, P less than 0.05 was considered significant. Augmented lipolysis contributes to insulin resistance and glucose intolerance observed in mice exposed to IH. Acipimox treatment ameliorated the metabolic consequences of IH and might represent a novel treatment option for patients with obstructive sleep apnea.
Validating the "Two Faces" of Envy: The Effect of Self-Control.
Envy drives different behaviors, and while we often emphasize the negative effects of envy, there are also relatively positive aspects. This study explored the "two faces" of envy or behaviors that improve oneself or degrade others. In study 1 (N=466, 45.1% males and 54.9% females; M age=18.53, SD age=2.05), we modeled the effects of envy and self-control on effort and aggression. In study 2 (N=102, 51% males and 49% females; M age=20.56, SD age=1.88), we explored the influence of envy on striving behavior and aggressive behavior using an ego depletion paradigm. The different effects of envy on different levels were doubly verified. We established structural equation models of the interactions of benign envy, malicious envy, self-control, and associated behaviors, and we found that: (1) Individuals' striving behavior was only affected by benign envy; (2) Individuals' aggressive behavior was influenced by both malicious envy and self-control. Ego depletion moderated the effect of malicious envy on aggressive behavior.
Antiviral characteristics of GSK1265744, an HIV integrase inhibitor dosed orally or by long-acting injection.
GSK1265744 is a new HIV integrase strand transfer inhibitor (INSTI) engineered to deliver efficient antiviral activity with a once-daily, low-milligram dose that does not require a pharmacokinetic booster. The in vitro antiviral profile and mechanism of action of GSK1265744 were established through integrase enzyme assays, resistance passage experiments, and cellular assays with site-directed molecular (SDM) HIV clones resistant to other classes of anti-HIV-1 agents and earlier INSTIs. GSK1265744 inhibited HIV replication with low or subnanomolar efficacy and with a selectivity index of at least 22,000 under the same culture conditions. The protein-adjusted half-maximal inhibitory concentration (PA-EC50) extrapolated to 100% human serum was 102 nM. When the virus was passaged in the presence of GSK1265744, highly resistant mutants with more than a 10-fold change (FC) in EC50 relative to that of the wild-type were not observed for up to 112 days of culture. GSK1265744 demonstrated activity against SDM clones containing the raltegravir (RAL)-resistant Y143R, Q148K, N155H, and G140S/Q148H signature variants (FC less than 6.1), while these mutants had a high FC in the EC50 for RAL (11 to >130). Either additive or synergistic effects were observed when GSK1265744 was tested in combination with representative anti-HIV agents, and no antagonistic effects were seen. These findings demonstrate that, similar to dolutegravir, GSK1265744 is differentiated as a new INSTI, having a markedly distinct resistance profile compared with earlier INSTIs, RAL, and elvitegravir (EVG). The collective data set supports further clinical development of GSK1265744.
Age, gender, and socioeconomic gradients in metabolic syndrome: biomarker evidence from a large sample in Taiwan, 2005-2013.
Purpose: To examine the age and gender heterogeneities in the association between socioeconomic status (SES) and the risk of metabolic syndrome (MetS) with biomarker data from Taiwan. Methods: Subjects included 102,201 men and 112,015 women aged 25 and above, from the 2005-2013 MJ Health Survey in Taiwan. SES was measured by education and family income. MetS was defined by the Adult Treatment Panel III criteria for Asian population. Logistic regression analyses were performed by age and gender groups. Results: (1) Higher education level was associated with significantly lower risk of MetS. (2) Higher income was associated with lower MetS risk among women aged under 65, but no association among men of all ages. (3) SES gradients were generally much stronger among women than among men of the same age group. (4) SES gradients reduced over the life course with the exception that income gradient remains flat among men of all ages. Conclusions: Among Chinese in Taiwan, the gender and age heterogeneities in the SES gradients in MetS are similar to those reported for Western societies. This cross-cultural convergence is broadly consistent with the general hypothesis that social conditions are fundamental causes of diseases and health disparities.
Do we need to accurately perceive our heartbeats? Cardioceptive accuracy and sensibility are independent from indicators of negative affectivity, body awareness, body image dissatisfaction, and alexithymia.
Assessment of the acuity of heartbeat perception, dubbed cardioceptive accuracy, as well as its association with various psychological characteristics are hot topics of interoception research. In this study, we aimed (1) to replicate previously reported findings on the association between the mental tracking task and a novel motor tracking task that eliminates disturbing tactile sensations; and (2) to explore associations between performance in the latter task and indicators of negative affectivity (anxiety, depression, anxiety sensitivity, somatic symptom distress), alexithymia, body focus, and dissatisfaction with body image. 102 young people (age = 20.8±5.08 yrs) participated in the study. Mental tracking score was significantly higher than motor tracking scores, although they were strongly associated. Frequentist correlation analysis showed no significant associations between indicators of cardioceptive accuracy and questionnaire scores; Bayesian analysis indicated the lack of association for the majority of the cases. Similarly, detectors and non-detectors showed no differences in any of the assessed characteristics and Bayesian results typically supported the lack of associations. In conclusion, cardioceptive accuracy, as assessed with different tracking methods, is not associated with the aforementioned self-reported characteristics in young individuals.
Telling life stories: a dyadic intervention for older Korean couples affected by mild Alzheimer's disease.
ABSTRACTBackground:Dementia has negative consequences for both persons with dementia and their family caregivers. Dyadic interventions in which both groups participate together have shown an effective and promising approach. The Couples Life Story Approach (CLSA) that was recently developed for older couples dealing with dementia in the USA was adapted and implemented for the older Korean population in this study. The purpose of this paper is to understand how older Korean couples dealing with dementia experienced the CLSA. Method: Fifty six couples (n = 102) completed the five-week intervention from December 2013 to October 2015. The participants completed a survey including open-ended questions one week after finishing the intervention. A thematic content analysis was conducted to analyze the responses. Results: Qualitative analysis revealed benefits and challenges in the experience of CLSA. Themes related to benefits were: (1) emotional benefits of reminiscing; (2) positive evaluation of life as a couple; (3) gratitude toward spouse; (4) changes in communications or activities with spouse; and (5) changes in relationship quality. Couples' experience varied, with some having mixed feelings about the intervention. Challenges perceived by participants included revival of bitterness and identification of loss. Conclusions: Findings suggest the CLSA contributes to enhancing the quality of life for couples affected by Alzheimer's disease and improving their relationship. Challenges that emerged in the CLSA will guide future research to identify the sub-population that is appropriate for the couple-oriented intervention in dementia care.
Suicide in children and young people in England: a consecutive case series.
Background: There is concern about the mental health of children and young people and a possible rise in suicidal behaviour in this group. We have done a comprehensive national multi-agency study of suicide in under 20s in England. We aimed to establish how frequently suicide is preceded by child-specific and young person-specific suicide risk factors, as well as all-age factors, and to identify contact with health-care and social-care services and justice agencies. Methods: This study is a descriptive examination of suicide in a national consecutive sample of children and young people younger than 20 years who died by suicide in England between Jan 1, 2014, and April 30, 2015. We obtained general population mortality data from the Office for National Statistics (ONS). We collected information about antecedents considered to be relevant to suicide (eg, abuse, bullying, bereavement, academic pressures, self-harm, and physical health) from a range of investigations and inquiries, including coroner inquest hearings, child death investigations, criminal justice system reports, and the National Health Service, including data on people in contact with mental health services in the 12 months before their death. Findings: 145 suicides in people younger than 20 years were notified to us during the study period, of which we were able to obtain report data about antecedents for 130 (90%). The number of suicides rose sharply during the late teens with 79 deaths by suicide in people aged 18-19 years compared with 66 in people younger than 18 years. 102 (70%) deaths were in males. 92 (63%) deaths were by hanging. Various antecedents were reported among the individuals for whom we had report data, including academic (especially exam) pressures (35 [27%] individuals), bullying (28 [22%]), bereavement (36 [28%]), suicide in family or friends (17 [13%]), physical health conditions (47 [36%]), family problems (44 [34%]), social isolation or withdrawal (33 [25%]), child abuse or neglect (20 [15%]), excessive drinking (34 [26%]), and illicit drug use (38 [29%]). Suicide-related internet use was recorded in 30 (23%) cases. In the week before death 13 (10%) individuals had self-harmed and 35 (27%) had expressed suicidal ideas. 56 (43%) individuals had no known contact with health-care and social-care services or justice agencies. Interpretation: Improved services for self-harm and mental health are crucial to suicide prevention, but the wide range of antecedents emphasises the roles of schools, primary care, social services, and the youth justice system. Funding: The Healthcare Quality Improvement Partnership.
Pregnancy and Motherhood During Surgical Training.
Importance: Although family priorities influence specialty selection and resident attrition, few studies describe resident perspectives on pregnancy during surgical training. Objective: To directly assess the resident experience of childbearing during training. Design, setting, and participants: A self-administered 74-question survey was electronically distributed in January 2017 to members of the Association of Women Surgeons, to members of the Association of Program Directors in Surgery listserv, and through targeted social media platforms. Surgeons who had 1 or more pregnancies during an Accreditation Council for Graduate Medical Education-accredited US general surgery residency program and completed training in 2007 or later were included. Important themes were identified using focus groups of surgeons who had undergone pregnancy during training in the past 7 years. Additional topics were identified through MEDLINE searches performed from January 2000 to July 2016 combining the keywords pregnancy, resident, attrition, and parenting in any specialty. Main outcomes and measures: Descriptive data on perceptions of work schedule during pregnancy, maternity leave policies, lactation and childcare support, and career satisfaction after childbirth. Results: This study included 347 female surgeons (mean [SD] age, 30.5 [2.7] years) with 452 pregnancies. A total of 297 women (85.6%) worked an unmodified schedule until birth, and 220 (63.6%) were concerned that their work schedule adversely affected their health or the health of their unborn child. Residency program maternity leave policies were reported by 121 participants (34.9%). A total of 251 women (78.4%) received maternity leave of 6 weeks or less, and 250 (72.0%) perceived the duration of leave to be inadequate. The American Board of Surgery leave policy was cited as a major barrier to the desired length of leave by 268 of 326 respondents (82.2%). Breastfeeding was important to 329 (95.6%), but 200 (58.1%) stopped earlier than they wished because of poor access to lactation facilities and challenges leaving the operating room to express milk. Sixty-four women (18.4%) had institutional support for childcare, and 231 (66.8%) reported a desire for greater mentorship on integrating a surgical career with motherhood and pregnancy. A total of 135 (39.0%) strongly considered leaving surgical residency, and 102 (29.5%) would discourage female medical students from a surgical career, specifically because of the difficulties of balancing pregnancy and motherhood with training. Conclusions and relevance: The challenges of having children during surgical residency may have significant workforce implications. A deeper understanding is critical to prevent attrition and to continue recruiting talented students. This survey characterizes these issues to help design interventions to support childbearing residents.
An Ecological Momentary Intervention for Smoking Cessation: Evaluation of Feasibility and Effectiveness.
Background: Despite substantial public health progress in reducing the prevalence of smoking in the United States overall, smoking among socioeconomically disadvantaged adults remains high. Objective: To determine the feasibility and preliminary effectiveness of a novel smartphone-based smoking cessation app designed for socioeconomically disadvantaged smokers. Methods: Participants were recruited from a safety-net hospital smoking cessation clinic in Dallas, Texas, and were followed for 13 weeks. All participants received standard smoking cessation clinic care (ie, group counseling and cessation pharmacotherapy) and a smartphone with a novel smoking cessation app (ie, Smart-T). The Smart-T app prompted 5 daily ecological momentary assessments (EMAs) for 3 weeks (ie, 1 week before cessation and 2 weeks after cessation). During the precessation period, EMAs were followed by messages that focused on planning and preparing for the quit attempt. During the postcessation period, participant responses to EMAs drove an algorithm that tailored messages to the current level of smoking lapse risk and currently present lapse triggers (eg, urge to smoke, stress). Smart-T offered additional intervention features on demand (eg, one-click access to the tobacco cessation quitline; "Quit Tips" on coping with urges to smoke, mood, and stress). Results: Participants (N=59) were 52.0 (SD 7.0) years old, 54% (32/59) female, and 53% (31/59) African American, and 70% (40/57) had annual household income less than US $16,000. Participants smoked 20.3 (SD 11.6) cigarettes per day and had been smoking for 31.6 (SD 10.9) years. Twelve weeks after the scheduled quit date, 20% (12/59) of all participants were biochemically confirmed abstinent. Participants responded to 87% of all prompted EMAs and received approximately 102 treatment messages over the 3-week EMA period. Most participants (83%, 49/59) used the on-demand app features. Individuals with greater nicotine dependence and minority race used the Quit Tips feature more than their counterparts. Greater use of the Quit Tips feature was linked to nonabstinence at the 2 (P=.02), 4 (P<.01), and 12 (P=.03) week follow-up visits. Most participants reported that they actually used or implemented the tailored app-generated messages and suggestions (83%, 49/59); the app-generated messages were helpful (97%, 57/59); they would like to use the app in the future if they were to lapse (97%, 57/59); and they would like to refer friends who smoke to use the Smart-T app (85%, 50/59). A minority of participants (15%, 9/59) reported that the number of daily assessments (ie, 5) was "too high." Conclusions: This novel just-in-time adaptive intervention delivered an intensive intervention (ie, 102 messages over a 3-week period), was well-liked, and was perceived as helpful and useful by socioeconomically disadvantaged adults who were seeking smoking cessation treatment. Smartphone apps may be used to increase treatment exposure and may ultimately reduce tobacco-related health disparities among socioeconomically disadvantaged adults.
Sleep phenotype of individuals with autism spectrum disorder bearing mutations in the PER2 circadian rhythm gene.
The Per family of genes functions as a primary circadian rhythm maintenance in the brain. Mutations in PER2 are associated with familial advanced sleep-phase syndrome 1 (FASPS1), and recently suggested in delayed sleep phase syndrome and idiopathic hypersomnia. The detection of PER2 variants in individuals with autism spectrum disorder (ASD) and without reported sleep disorders, has suggested a role of circadian-relevant genes in the pathophysiology of ASD. It remains unclear whether these individuals may have, in addition to ASD, an undiagnosed circadian rhythm sleep disorder. The MSSNG database was used to screen whole genome sequencing data of 5,102 individuals with ASD for putative mutations in PER2. Families identified were invited to complete sleep phenotyping consisting of a structured interview and two standardized sleep questionnaires: the Pittsburgh Sleep Quality Index and the Morningness-Eveningness Questionnaire. From 5,102 individuals with ASD, two nonsense, one frameshift, and one de novo missense PER2 variants were identified (0.08%). Of these four, none had a diagnosed sleep disorder. Three reported either a history of, or ongoing sleep disturbances, and one had symptoms highly suggestive of FASPS1 (as did a mutation carrier father without ASD). The individual with the missense variant did not report sleep concerns. The ASD and cognitive profiles of these individuals varied in severity and symptoms. The results support a possible role of PER2-related circadian rhythm disturbances in the dysregulation of sleep overall and sometimes FASPS1. The relationship between dysregulated sleep and the pathophysiology of ASD require further exploration.
Recognition of Emotions Conveyed by Touch Through Force-Sensitive Screens: Observational Study of Humans and Machine Learning Techniques.
Background: Emotions affect our mental health: they influence our perception, alter our physical strength, and interfere with our reason. Emotions modulate our face, voice, and movements. When emotions are expressed through the voice or face, they are difficult to measure because cameras and microphones are not often used in real life in the same laboratory conditions where emotion detection algorithms perform well. With the increasing use of smartphones, the fact that we touch our phones, on average, thousands of times a day, and that emotions modulate our movements, we have an opportunity to explore emotional patterns in passive expressive touches and detect emotions, enabling us to empower smartphone apps with emotional intelligence. Objective: In this study, we asked 2 questions. (1) As emotions modulate our finger movements, will humans be able to recognize emotions by only looking at passive expressive touches? (2) Can we teach machines how to accurately recognize emotions from passive expressive touches? Methods: We were interested in 8 emotions: anger, awe, desire, fear, hate, grief, laughter, love (and no emotion). We conducted 2 experiments with 2 groups of participants: good imagers and emotionally aware participants formed group A, with the remainder forming group B. In the first experiment, we video recorded, for a few seconds, the expressive touches of group A, and we asked group B to guess the emotion of every expressive touch. In the second experiment, we trained group A to express every emotion on a force-sensitive smartphone. We then collected hundreds of thousands of their touches, and applied feature selection and machine learning techniques to detect emotions from the coordinates of participant' finger touches, amount of force, and skin area, all as functions of time. Results: We recruited 117 volunteers: 15 were good imagers and emotionally aware (group A); the other 102 participants formed group B. In the first experiment, group B was able to successfully recognize all emotions (and no emotion) with a high 83.8% (769/918) accuracy: 49.0% (50/102) of them were 100% (450/450) correct and 25.5% (26/102) were 77.8% (182/234) correct. In the second experiment, we achieved a high 91.11% (2110/2316) classification accuracy in detecting all emotions (and no emotion) from 9 spatiotemporal features of group A touches. Conclusions: Emotions modulate our touches on force-sensitive screens, and humans have a natural ability to recognize other people's emotions by watching prerecorded videos of their expressive touches. Machines can learn the same emotion recognition ability and do better than humans if they are allowed to continue learning on new data. It is possible to enable force-sensitive screens to recognize users' emotions and share this emotional insight with users, increasing users' emotional awareness and allowing researchers to design better technologies for well-being.
Frailty Screening in the Community Using the FRAIL Scale.
Objectives: To explore the feasibility of using the FRAIL scale in community screening of older Chinese people aged 65 years and older, followed by clinical validation by comprehensive geriatric assessment of those classified as pre-frail or frail. Design: Two-phase study: screening of people aged 65 years and older by trained volunteers, followed by comprehensive geriatric assessment by multidisciplinary staff for those classified as pre-frail or frail. Setting: Elderly Centers in the New Territories East Region of Hong Kong SAR China. Participants: A total of 816 members of elderly centers attending by themselves or accompanied by relatives. Measurements: For phase 1, questionnaire (including demographic, lifestyle, chronic diseases) and screening tools were administered by trained volunteers. These consist of the FRAIL scale, SARC-F to screen for sarcopenia, and mild cognitive impairment using the abbreviated screening for mild cognitive impairment (Abbreviated Memory Inventory for the Chinese). Blood pressure, body mass index, and grip strength were recorded. For phase 2, comprehensive geriatric assessment include questionnaires assessing lifestyle domain (physical activity, nutritional status using the Mini-Nutritional Assessment-Short Form), the physical domain (number of diseases and number of drugs, activities of daily living and instrumental activities of daily living disabilities, geriatric syndromes, self-rated health, sleep quality), cognitive and psychological domain (Mini-Mental State Examination, Geriatric Depression Scale), and social domain (income, housing, living satisfaction, family support). Results: The prevalence of pre-frailty and frailty were 52.4% and 12.5%, respectively. The prevalence for frailty increasing with age from 5.1% for those aged 65-69 years to 16.8% for those ≥75, being greater in women compared with men (13.9% vs 4.2%). Of those who were pre-frail or frail (n = 529), 42.5% had sarcopenia and 60.7% had mild cognitive impairment. Among those who were frail (n = 102), sarcopenia and mild cognitive impairment were also frequently present: 12.8% had sarcopenia, 14.7% had mild cognitive impairment, 63.7% had both sarcopenia and mild cognitive impairment, and only 8.8% had neither. In phase 2, participants who were classified as pre-frail or frail (n = 529) were invited for further interviews; 255 participants (48.2%) returned. Compared with the pre-frail group, those in the frail group were less physically active, had higher number of chronic diseases, were taking more medications (more were taking sleeping pills), reported more falls, rated their health as poor, had higher prevalence of depressive symptoms and mild cognitive impairment, had higher prevalence of sarcopenia, and a high number of activities of daily living and instrumental activities of daily living disabilities. Conclusion: The FRAIL scale may be used as the first step in a step care approach to detecting frailty in the community, allowing targeted intervention to potentially retard decline and future disability.
The Culture is Prevention Project: measuring cultural connectedness and providing evidence that culture is a social determinant of health for Native Americans.
Background: It is important for non-Native persons to understand that the meaning of culture to Native American/Indigenous Peoples is not about esteem, taste or music but rather is described as a cognitive map on how to be. Native American/Indigenous culture can be thought of as all the things and ways in which Native/Indigenous people understand who they are, where they come from and how they are to interact with others. Hundreds of years across many generations have taught that culture-based activities and interventions improve Native/Indigenous health and wellbeing. We explore if increased Native American culture/cultural connectedness is associated with better mental health/well-being and physical health. Methods: We analyzed data from a two-phased study (N = 259 and N = 102) of 361 urban Native Americans in California (2018-2021). The 29 items validated Cultural Connectedness Scale-California (CCS-CA) measured Native culture/cultural connectedness. Mental health/well-being and physical health were assessed using the: modified Herth Hope Index (mHHI), Satisfaction with Life (SWL), Center for Epidemiologic Studies Depression Scale-Revised (CESD-R-10), Substance Abuse (CAGE-AID), and Health Related Quality of Life (HRQOL). We conducted Pearson correlations and stepwise regression analyses with CCS-CA as the independent (predictor) variable to explore our main research questions: 1) Is increased Native American/Indigenous culture associated with: 1) better mental health/well-being; and 2) better physical health? Results: Increased Native/Indigenous culture (CCS-CA scores) is significantly associated with better mental health/well-being (mHHI, p < .001) and satisfaction with life (SWL, p < .001) predicts good physical health days (HRQOL, p < .001). Increased connection to Native American/Indigenous culture (CCS-CA scores) is significantly associated with decreased risk for depression (CESD-R-10, p < .0) and substance abuse and (CAGE-AID, p < .07). Significant results for culture as protective against risk for substance abuse (CAGE-AID) was most likely affected (p value approaching significance) due to an error in language on the measure (i.e., created double negative). Conclusions: Native American/Indigenous culture is a predictor of improved outcomes for mental health/well-being and physical healthy days. Native culture is an important social determinant of health. We add to the evidence that Native/Indigenous culture (i.e., cultural connectedness) be considered an important intervention objective and health-related outcome measure.
Women Oncologists' Perceptions and Factors Associated With Decisions to Pursue Academic vs Nonacademic Careers in Oncology.
Importance: Women outnumber men in US medical school enrollment, but they represent less than 40% of academic oncology faculty. Objective: To identify the key factors associated with female oncologists' decision to pursue academic or nonacademic oncology practice and to characterize their perceptions about their current career. Design, setting, and participants: This cross-sectional survey study was distributed through email and social media to female physicians in academic and nonacademic oncology practice in the United States. The survey was open for 3 months, from August 1 to October 31, 2020. Main outcomes and measures: No single primary study outcome was established because of the cross-sectional nature of the survey. Data were collected anonymously and analyzed using t tests for continuous variables and χ2 tests for categorical variables. Results: Among the 667 female respondents, 422 (63.2%) identified as academic oncologists and 245 (36.8%) identified as nonacademic oncologists. Approximately 25% of respondents reported that their spouse or partner (156 [23.5%]) and/or family (176 [26.4%]) extremely or moderately affected their decision to pursue academic practice. Academic oncologists perceived the biggest sacrifice of pursuing academics to be time with loved ones (181 [42.9%]). Nonacademic oncologists perceived the biggest sacrifice of pursuing academics to be pressure for academic promotion (102 [41.6%]). Respondents had different perceptions of how their gender affected their ability to obtain a chosen job, with 116 academic oncologists (27.6%) and 101 nonacademic oncologists (41.2%) reporting a positive or somewhat positive impact (P = .001). More than half of the women surveyed (54.6% academic oncologists [230]; 50.6% nonacademic oncologists [123]; P = .61) believed they were less likely to be promoted compared with male colleagues. Academic and nonacademic oncologists reported rarely or never having a sense of belonging in their work environment (33 [7.9%] and 5 [2.0%]; P < .001). Most respondents reported that they would choose the same career path again (301 academic oncologists [71.3%]; 168 nonacademic oncologists [68.6%]); however, 92 academic oncologists (21.9%) reported they were likely to pursue a career outside of academic oncology in the next 5 years. Conclusions and relevance: This survey study found that a spouse or partner and/or family were factors in the career choice of both academic and nonacademic oncologists and that female gender was largely perceived to adversely affect job promotion. Given that more than 20% of female academic oncologists were considering leaving academia, gender inequality is at high risk of continuing if the culture is not addressed.
They Saw It Coming: Rising Trends in Depression, Anxiety, and Suicidality in Creative Students and Potential Impact of the COVID-19 Crisis.
Previous research has established that creative adolescents are generally low in neuroticism and as well-adjusted as their peers. From 2006 to 2013, data from cohorts of creative adolescents attending a counseling laboratory supported these results. Clinical findings of increased anxiety, depression, and suicidality among creative students in 2014 led the researchers to create 3 studies to explore these clinical findings. Once artifactual causes of these changes were ruled out, a quantitative study was conducted. Study 1, an analysis of mean differences of pre-2014 and post-2014 cohorts showed that post-2014 cohorts scored significantly higher in Neuroticism, Openness to Experience, and Conscientiousness and lower in Extraversion on Big 5 inventories. Regression analyses suggested that while Neuroticism was associated with gender, Conscientiousness and Grade Point Average for the earlier group, Neuroticism in the post 2014 groups was related to complex interplay of all personality dynamics except Agreeableness. In the qualitative Study 2, focus groups of 6-10 students, for a total of 102 participants were queried about the reasons they perceived for increased anxiety and depression in creative students. Increased achievement pressures and awareness of environmental and social problems were major sources of external stressors; perfectionism and desire to fulfill expectations of others were the primary sources of internal stress. The authors suggest that creative students' openness to experience and advanced knowledge made it possible for these students to see the potential for environmental and social crises and respond to their inability to solve these problems with anxiety and depression. Study 3 was a qualitative study that followed up 19 participants from the post-2014 cohort to explore the impact of the COVID-19 pandemic on mental health and creativity. While the majority perceived a negative effect of the pandemic on their mental health, most also produced a surprising variety of creative works during that time. In conclusion, rapid changes in the lives of creative adolescents since 2014 suggest that scholars focus on current cohorts and the ways in which adolescent personality is shaped by internal expectation and external pressures and global events. Despite the pandemic, creative young people continued to create.
Waist circumference, abdominal obesity, and depression among overweight and obese U.S. adults: National Health and Nutrition Examination Survey 2005-2006.
Background: Obesity is associated with an increased risk of mental illness; however, evidence linking body mass index (BMI)-a measure of overall obesity, to mental illness is inconsistent. The objective of this study was to examine the association of depressive symptoms with waist circumference or abdominal obesity among overweight and obese U.S. adults. Methods: A cross-sectional, nationally representative sample from the 2005-2006 National Health and Nutrition Examination Survey was used. We analyzed the data from 2,439 U.S. adults (1,325 men and 1,114 nonpregnant women) aged ≥ 20 years who were either overweight or obese with BMI of ≥ 25.0 kg/m2. Abdominal obesity was defined as waist circumference of > 102 cm for men and > 88 cm for women. Depressive symptoms (defined as having major depressive symptoms or moderate-to-severe depressive symptoms) were assessed by the Patient Health Questionnaire-9 diagnostic algorithm. The prevalence and the odds ratios (ORs) with 95% confidence intervals (CIs) for having major depressive symptoms and moderate-to-severe depressive symptoms were estimated using logistic regression analysis. Results: After multivariate adjustment for demographics and lifestyle factors, waist circumference was significantly associated with both major depressive symptoms (OR: 1.03, 95% CI: 1.01-1.05) and moderate-to-severe depressive symptoms (OR: 1.02, 95% CI: 1.01-1.04), and adults with abdominal obesity were significantly more likely to have major depressive symptoms (OR: 2.18, 95% CI: 1.35-3.59) or have moderate-to-severe depressive symptoms (OR: 2.56, 95% CI: 1.34-4.90) than those without. These relationships persisted after further adjusting for coexistence of multiple chronic conditions and persisted in participants who were overweight (BMI: 25.0-< 30.0 kg/m2) when stratified analyses were conducted by BMI status. Conclusion: Among overweight and obese U.S. adults, waist circumference or abdominal obesity was significantly associated with increased likelihoods of having major depressive symptoms or moderate-to-severe depressive symptoms. Thus, mental health status should be monitored and evaluated in adults with abdominal obesity, particularly in those who are overweight.
Children's fearfulness as a moderator of parenting in early socialization: Two longitudinal studies.
Findings from 2 longitudinal studies replicate and considerably extend past work on child temperament as a moderating link between parenting and successful socialization outcomes. In Study 1 (N = 106 mothers and children), child fearfulness, mother-child positive relationship, and maternal power assertion were assessed at 22 and 33 months; the outcome--children's moral self--was assessed at 56 months. In Study 2 (N = 102 mothers, fathers, and children), child fearfulness and parent-child positive relationship were assessed at 7 and 15 months; parents' power assertion was assessed at 15 months. The outcomes were children's receptive, willing stance toward the parent at 25 months, and rule-compatible conduct without supervision at 38 months. Child fearfulness significantly moderated the impact of parenting: In both studies, for relatively fearless children, mother-child positive relationship predicted future successful socialization outcomes in mother-child dyads. There was no analogous moderation effect in father-child dyads in Study 2. For relatively fearful children, fathers' power assertion in Study 2 predicted poor socialization outcomes. All Temperament x Parenting interactions appeared limited to measures obtained in the 2nd year.
Pathways between internalized stigma and outcomes related to recovery in schizophrenia spectrum disorders.
Objective: The mechanisms by which internalized stigma affects outcomes related to recovery among people with severe mental illness have yet to be explicitly studied. This study empirically evaluated a model for how internalized stigma affects important outcomes related to recovery. Methods: A total of 102 persons with schizophrenia spectrum disorders completed measures of internalized stigma, awareness of mental illness, psychiatric symptoms, self-esteem, hopefulness, and coping. Path analyses tested a predicted model and an alternative model for the relationships between the variables. Results: Results from model 1 supported the view that internalized stigma increases avoidant coping, active social avoidance, and depressive symptoms and that these relationships are mediated by the impact of internalized stigma on hope and self-esteem. Results from model 2 replicated significant relationships from model 1 but also supported the hypothesis that positive symptoms may influence hope and self-esteem. Conclusions: Findings from two models supported the hypothesis that internalized stigma affects hope and self-esteem, leading to negative outcomes related to recovery. It is recommended that interventions be developed and tested to address the important effects of internalized stigma on recovery.
Inter-individual differences in resting-state functional connectivity predict task-induced BOLD activity.
The resting brain exhibits coherent patterns of spontaneous low-frequency BOLD fluctuations. These so-called resting-state functional connectivity (RSFC) networks are posited to reflect intrinsic representations of functional systems commonly implicated in cognitive function. Yet, the direct relationship between RSFC and the BOLD response induced by task performance remains unclear. Here we examine the relationship between a region's pattern of RSFC across participants and that same region's level of BOLD activation during an Eriksen Flanker task. To achieve this goal we employed a voxel-matched regression method, which assessed whether the magnitude of task-induced activity at each brain voxel could be predicted by measures of RSFC strength for the same voxel, across 26 healthy adults. We examined relationships between task-induced activation and RSFC strength for six different seed regions [Fox, M.D., Snyder, A.Z., Vincent, J.L., Corbetta, M., Van Essen, D.C., Raichle, M.E., 2005. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc. Natl. Acad. Sci. U. S. A. 102, 9673-9678.], as well as the "default mode" and "task-positive" resting-state networks in their entirety. Our results indicate that, for a number of brain regions, inter-individual differences in task-induced BOLD activity were predicted by one of two resting-state properties: (1) the region's positive connectivity strength with the task-positive network, or (2) its negative connectivity with the default mode network. Strikingly, most of the regions exhibiting a significant relationship between their RSFC properties and task-induced BOLD activity were located in transition zones between the default mode and task-positive networks. These results suggest that a common mechanism governs many brain regions' neural activity during rest and its neural activity during task performance.