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حَدَّثَنَا عُبَيْدُ اللَّهِ بْنُ مُعَاذٍ، حَدَّثَنَا خَالِدٌ، حَدَّثَنَا شُعْبَةُ، عَنْ خُبَيْبِ بْنِ عَبْدِ الرَّحْمَنِ، قَالَ سَمِعْتُ حَفْصَ بْنَ عَاصِمٍ، يُحَدِّثُ عَنْ أَبِي سَعِيدِ بْنِ الْمُعَلَّى، أَنَّ النَّبِيَّ صلى الله عليه وسلم مَرَّ بِهِ وَهُوَ يُصَلِّي فَدَعَاهُ قَالَ فَصَلَّيْتُ ثُمَّ أَتَيْتُهُ قَالَ فَقَالَ ‏"‏ مَا مَنَعَكَ أَنْ تُجِيبَنِي ‏"‏ ‏.‏ قَالَ كُنْتُ أُصَلِّي ‏.‏ قَالَ ‏"‏ أَلَمْ يَقُلِ اللَّهُ عَزَّ وَجَلَّ ‏{‏ يَا أَيُّهَا الَّذِينَ آمَنُوا اسْتَجِيبُوا لِلَّهِ وَلِلرَّسُولِ إِذَا دَعَاكُمْ لِمَا يُحْيِيكُمْ ‏}‏ لأُعَلِّمَنَّكَ أَعْظَمَ سُورَةٍ مِنَ الْقُرْآنِ أَوْ فِي الْقُرْآنِ ‏"‏ ‏.‏ شَكَّ خَالِدٌ ‏"‏ قَبْلَ أَنْ أَخْرُجَ مِنَ الْمَسْجِدِ ‏"‏ ‏.‏ قَالَ قُلْتُ يَا رَسُولَ اللَّهِ قَوْلَكَ ‏.‏ قَالَ ‏"‏ ‏{‏ الْحَمْدُ لِلَّهِ رَبِّ الْعَالَمِينَ ‏}‏ وَهِيَ السَّبْعُ الْمَثَانِي الَّتِي أُوتِيتُ وَالْقُرْآنُ الْعَظِيمُ ‏"‏ ‏.‏

Abu Sa'id b. al-Mu'alla said that when he was praying the Prophet (ﷺ) passed by him and he called him. He said:I prayed ant then I came to him. He asked: What prevented you from answering me ? He replied: I was praying. He said: Has not Allah said: "O you who believe, respond to Allah and the Apostle when he calls you to that which gives you life ? (8:24) Let me teach you the greatest surah from the Qur'an or in the Qur'an (the narrator Khalid doubted) before I leave the mosque. I said: (I shall memorize) your saying. He said: It is: "Praise be to Allah, the Lord of the Universe" which is the seven oft-repeated verses, and the mighty Qur'an

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A nonrandomized controlled clinical pilot trial on 8 wk of intermittent fasting (24 h/wk).

Objective: The aim of the study was to evaluate whether intermittent fasting (IF) is an effective preventive measure, and whether it is feasible for healthy volunteers under every day conditions. Methods: A nonrandomized controlled clinical trial on IF was performed with healthy volunteers over a period of 8 wk, and a subsequent 4-mo follow-up. Outcomes were assessed at baseline, after 8 wk, and after 6 mo. Volunteers who were not interested in fasting served as a control group. Participants in the fasting group were asked to continue their regular nutritional habits on the nonfasting days, whereas the control group maintained their habitual nutrition throughout the whole period. Outcomes included changes of metabolic parameters (insulin, glucose, insulin resistance, insulin-like growth factor-1, brain-derived neurotropic factor, lipids, liver enzymes, hemoglobin A1c) and coagulation markers; bioelectrical impedance analysis; body mass index; abdominal girth; blood pressure; general quality of life (five-item World Health Organization Well-Being Index [WHO-5] questionnaire), as well as mood and anxiety (Hospital Anxiety and Depression Scale [HADS], Profile of Mood States, Flourishing-Scale, visual analog scale, Likert scales). The intervention consisted of a fasting day, which was repeated every week for 8 wk, with abstinence from solid food between 00:00 and 23:59 at minimum and a maximum caloric intake of 300 kcal on each fasting day. A per-protocol analysis was performed. P < 0.05 was considered significant. Results: Thirty-six volunteers were included; 22 allocated themselves to the fasting group, and 14 to the control group. Thirty-three data sets were included in the final analysis. Although significant in-group changes were observed in both groups for a number of outcomes after 8 wk and 6 mo, no significant between-group differences were observed for any outcome other than overall body fat mass after 8 wk as well as for the HADS total score and the WHO-5 total score after 6 mo, all in favor of the fasting group. However, none of the between-group differences were clinically relevant. Conclusions: We did not find any clinically relevant differences between groups in this controlled clinical pilot trial of 8 wk of IF in healthy volunteers. Further clinical research in this field is warranted to further analyze mechanisms and effects of IF.

Nutrition (Burbank, Los Angeles County, Calif.) · randomised controlled trial · 27 citationsread the source →

Effect of Digital Cognitive Behavioral Therapy for Insomnia on Health, Psychological Well-being, and Sleep-Related Quality of Life: A Randomized Clinical Trial.

Importance: Digital cognitive behavioral therapy (dCBT) is a scalable and effective intervention for treating insomnia. Most people with insomnia, however, seek help because of the daytime consequences of poor sleep, which adversely affects quality of life. Objectives: To investigate the effect of dCBT for insomnia on functional health, psychological well-being, and sleep-related quality of life and to determine whether a reduction in insomnia symptoms was a mediating factor. Design, setting, and participants: This online, 2-arm, parallel-group randomized trial comparing dCBT for insomnia with sleep hygiene education (SHE) evaluated 1711 participants with self-reported symptoms of insomnia. Participants were recruited between December 1, 2015, and December 1, 2016, and dCBT was delivered using web and/or mobile channels plus treatment as usual; SHE comprised a website and a downloadable booklet plus treatment as usual. Online assessments took place at 0 (baseline), 4 (midtreatment), 8 (posttreatment), and 24 (follow-up) weeks. Programs were completed within 12 weeks after inclusion. Main outcomes and measures: Primary outcomes were scores on self-reported measures of functional health (Patient-Reported Outcomes Measurement Information System: Global Health Scale; range, 10-50; higher scores indicate better health); psychological well-being (Warwick-Edinburgh Mental Well-being Scale; range, 14-70; higher scores indicate greater well-being); and sleep-related quality of life (Glasgow Sleep Impact Index; range, 1-100; higher scores indicate greater impairment). Secondary outcomes comprised mood, fatigue, sleepiness, cognitive failures, work productivity, and relationship satisfaction. Insomnia was assessed with the Sleep Condition Indicator (range: 0-32; higher scores indicate better sleep). Results: Of the 1711 participants included in the intention-to-treat analysis, 1329 (77.7%) were female, mean (SD) age was 48.0 (13.8) years, and 1558 (91.1%) were white. Use of dCBT was associated with a small improvement in functional health compared with SHE (adjusted difference [95% CI] at week 4, 0.90 [0.40-1.40]; week 8, 1.76 [1.24-2.28]; week 24, 1.76 [1.22-2.30]) and psychological well-being (adjusted difference [95% CI] at week 4, 1.04 [0.28-1.80]; week 8, 2.68 [1.89-3.47]; week 24, 2.95 [2.13-3.76]), and with a large improvement in sleep-related quality of life (at week 4, -8.76 [-11.83 to -5.69]; week 8, -17.60 [-20.81 to -14.39]; week 24, -18.72 [-22.04 to -15.41]) (all P < .01). A large improvement in insomnia mediated these outcomes (range mediated, 45.5%-84.0%). Conclusions and relevance: Use of dCBT is effective in improving functional health, psychological well-being, and sleep-related quality of life in people reporting insomnia symptoms. A reduction in insomnia symptoms mediates these improvements. These results confirm that dCBT improves both daytime and nighttime aspects of insomnia, strengthening existing recommendations of CBT as the treatment of choice for insomnia. Trial registration: isrctn.org identifier: ISRCTN60530898.

JAMA psychiatry · randomised controlled trial · 314 citationsread the source →

Effects of internet-based pain coping skills training before home exercise for individuals with hip osteoarthritis (HOPE trial): a randomised controlled trial.

This assessor-, therapist-, and participant-blinded randomised controlled trial evaluated the effects of an automated internet-based pain coping skills training (PCST) program before home exercise for people with clinically diagnosed hip osteoarthritis. One hundred forty-four people were randomised to either the PCST group or the comparator group. In the first 8 weeks, the PCST group received online education and PCST, whereas the comparison group received online education only. From weeks 8 to 24, both groups visited a physiotherapist 5 times for home exercise prescription. Assessments were performed at baseline, 8, 24, and 52 weeks. Primary outcomes were hip pain on walking (11-point numerical rating scale) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) at 24 weeks. Secondary outcomes were other measures of pain, quality-of-life, global change, self-efficacy, pain coping, pain catastrophizing, depression, anxiety, stress, physical activity, and adverse events. Primary outcomes were completed by 137 (95%), 131 (91%), and 127 (88%) participants at 8, 24, and 52 weeks, respectively. There were no significant between-group differences in primary outcomes at week 24 (change in: walking pain [mean difference 0.5 units; 95% confidence interval, -0.3 to 1.3] and function [-0.9 units; 95% confidence interval, -4.8 to 2.9]), with both groups showing clinically relevant improvements. At week 8, the PCST group had greater improvements in function, pain coping, and global improvement than comparison. Greater pain coping improvements persisted at 24 and 52 weeks. In summary, online PCST immediately improved pain coping and function but did not confer additional benefits to a subsequent exercise program, despite sustained pain coping improvements.

Pain · randomised controlled trial · 54 citationsread the source →

Telephone-Based Cognitive Behavioral Therapy for Insomnia in Perimenopausal and Postmenopausal Women With Vasomotor Symptoms: A MsFLASH Randomized Clinical Trial.

Importance: Effective, practical, nonpharmacologic therapies are needed to treat menopause-related insomnia symptoms in primary and women's specialty care settings. Objective: To evaluate the efficacy of telephone-based cognitive behavioral therapy for insomnia (CBT-I) vs menopause education control (MEC). Design, setting, and participants: A single-site, randomized clinical trial was conducted from September 1, 2013, to August 31, 2015, in western Washington State among 106 perimenopausal or postmenopausal women aged 40 to 65 years with moderate insomnia symptoms (Insomnia Severity Index [ISI] score, ≥12) and 2 or more daily hot flashes. Blinded assessments were conducted at baseline, 8, and 24 weeks postrandomization. An intent-to-treat analysis was conducted. Interventions: Six CBT-I or MEC telephone sessions in 8 weeks. Participants submitted weekly electronic sleep diaries and received group-specific written educational materials. The CBT-I sessions included sleep restriction, stimulus control, sleep hygiene education, cognitive restructuring, and behavioral homework; MEC sessions provided information about menopause and women's health. Main outcomes and measures: Primary outcome was scores on the ISI (score range, 0-28; scores ≥15 indicate moderate to severe insomnia). Secondary outcome was scores on the Pittsburgh Sleep Quality Index (score range, 0-21; higher scores indicate worse sleep quality). Additional outcomes included sleep and hot flash diary variables and hot flash interference. Results: At 8 weeks, ISI scores had decreased 9.9 points among 53 women receiving CBT-I (mean [SD] age, 55.0 [3.5] years) and 4.7 points among 53 women receiving MEC (age, 54.7 [4.7] years), a mean between-group difference of 5.2 points (95% CI, -6.1 to -3.3; P < .001). Pittsburgh Sleep Quality Index scores decreased 4.0 points in women receiving CBT-I and 1.4 points in women receiving MEC, a mean between-group difference of 2.7 points (95% CI, -3.9 to -1.5; P < .001). Significant group differences were sustained at 24 weeks. At 8 and 24 weeks, 33 of 47 women (70%) and 37 of 44 (84%) in the CBT-I group, respectively, had ISI scores in the no-insomnia range compared with 10 of 41 (24%) and 16 of 37 (43%) in the MEC group, respectively. The CBT-I group also had greater improvements in diary-reported sleep latency, wake time, and sleep efficiency. There were no between-group differences in frequency of daily hot flashes, but hot flash interference was significantly decreased at 8 weeks for the CBT-I group (-15.7; 95% CI, -20.4 to -11.0) compared with the MEC group (-7.1; 95% CI, -14.6 to 0.4) (P = .03), differences that were maintained at 24 weeks for the CBT-I group (-22.8; 95% CI, -28.6 to -16.9) and MEC group (-11.6; 95% CI, -19.4 to -3.8) (P = .003). Conclusions and relevance: Telephone-based CBT-I improved sleep in perimenopausal and postmenopausal women with insomnia and hot flashes. Results support further development and testing of centralized CBT-I programs for treating menopausal insomnia. Trial registration: clinicaltrials.gov Identifier: NCT01936441.

JAMA internal medicine · randomised controlled trial · 114 citationsread the source →

Subacromial balloon spacer massive rotator cuff tear treatment systematic review and meta-analysis: Patient selection and physical therapy may be keys to outcome success.

Purpose: Subacromial balloon spacer implantation (SBSI) efficacy for massive rotator cuff tear treatment was evaluated based on perceived shoulder function, active shoulder mobility, pain, complications and research study methodological quality. The purpose was to better discern the efficacy of this device from both surgical and rehabilitative perspectives to improve patient outcomes. Methods: PubMed, EMBASE and Cochrane Library databases were searched (1 January 2010 to 1 June 2024) using 'balloon spacer', 'subacromial spacer', 'subacromial balloon spacer', 'shoulder spacer' and 'inspace' terms. Pre-surgery (baseline), 12-month (12-m) and 24-month (24-m) post-SBSI mean changes were compared using one-way ANOVA and Scheffe post hoc tests, and comparative study effect sizes were calculated (p ≤ 0.05). Results: This review consists of 27 studies with 894 patients (67.8 ± 5 years of age) and 29.4 ± 17-month follow-up. Modified Coleman Methodology Scores (MCMS) revealed fair overall quality (mean = 61.4 ± 11). Constant-Murley scores improved from 34.8 ± 6 (baseline), to 64.2 ± 9 (12-m) and 67.9 ± 8 (24-m) (12-m, 24-m > baseline, p < 0.001). ASES scores improved from 35.1 ± 14 (baseline), to 83.3 ± 7 (12-m) and 81.8 ± 5 (24-m)(12-m, 24-m > baseline, p < 0.001). VAS pain scores improved from 6.6 ± 1 (baseline), to 2.6 ± 1 (12-m) and 2.0 ± 1 (24-m) (12-m, 24-m < baseline, p < 0.001). Flexion increased from 108.5 ± 25° (baseline), to 128.5 ± 30° (12-m) and 151.2 ± 14° (24-m) (24-m > 12-m, baseline, p = 0.01). Abduction increased from 97.7 ± 24° (baseline) to 116.3 ± 23° (12-m) and 142.3 ± 15° (24-m) (24-m > 12-m, baseline, p = 0.02). External rotation (ER) in adduction changed from 33.1 ± 7° (baseline) to 32.5 ± 4° (12-m) and 53.9 ± 9° (24-m)(24-m > 12-m, baseline, p = 0.01). ER at 90° abduction increased from 56.3 ± 3° (baseline) to 83.5 ± 5° (12-m) and 77.1 ± 4° (24-m) (24-m, 12-m > baseline, p = 0.01). Comparison studies, however, displayed insignificant results with small effect sizes. Conclusion: Despite overall fair MCMS scores, at 24-m post-SBSI, shoulder function improved and pain decreased. More rigorous comparative studies, however, revealed insignificant findings. Patients with the potential to re-establish the essential glenohumeral joint force couple that depresses the humeral head on the glenoid fossa and who comply with physical therapy may be more likely to achieve success following SBSI. Level of evidence: Level IV.

Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA · meta-analysis · 3 citationsread the source →

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

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

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

Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder.

Background: Anecdotal reports suggest that psychedelic agents may relieve symptoms of obsessive-compulsive disorder (OCD). This modified double-blind study investigated the safety, tolerability, and clinical effects of psilocybin, a potent 5-HT(1A) and 5-HT(2A/2C) agonist, in patients with OCD. Method: Nine subjects with DSM-IV-defined OCD and no other current major psychiatric disorder participated in up to 4 single-dose exposures to psilocybin in doses ranging from sub-hallucinogenic to frankly hallucinogenic. Low (100 microg/kg), medium (200 microg/kg), and high (300 microg/kg) doses were assigned in that order, and a very low dose (25 microg/kg) was inserted randomly and in double-blind fashion at any time after the first dose. Testing days were separated by at least 1 week. Each session was conducted over an 8-hour period in a controlled environment in an outpatient clinic; subjects were then transferred to a psychiatric inpatient unit for overnight observation. The Yale-Brown Obsessive Compulsive Scale (YBOCS) and a visual analog scale measuring overall obsessive-compulsive symptom severity were administered at 0, 4, 8, and 24 hours post-ingestion. The Hallucinogen Rating Scale was administered at 8 hours, and vital signs were recorded at 0, 1, 4, 8, and 24 hours after ingestion. The study was conducted from November 2001 to November 2004. Results: Nine subjects were administered a total of 29 psilocybin doses. One subject experienced transient hypertension without relation to anxiety or somatic symptoms, but no other significant adverse effects were observed. Marked decreases in OCD symptoms of variable degrees were observed in all subjects during 1 or more of the testing sessions (23%-100% decrease in YBOCS score). Repeated-measures analysis of variance for all YBOCS values revealed a significant main effect of time on Wilks lambda (F = 9.86, df = 3,3; p = .046), but no significant effect of dose (F = 2.25, df = 3,3; p = .261) or interaction of time and dose (F = 0.923, df = 9,45; p = .515). Improvement generally lasted past the 24-hour timepoint. Conclusions: In a controlled clinical environment, psilocybin was safely used in subjects with OCD and was associated with acute reductions in core OCD symptoms in several subjects.

The Journal of clinical psychiatry · clinical trial · 441 citationsread the source →

Efficacy and safety of the muscarinic receptor agonist KarXT (xanomeline-trospium) in schizophrenia (EMERGENT-2) in the USA: results from a randomised, double-blind, placebo-controlled, flexible-dose phase 3 trial.

Background: New treatments with new mechanisms are urgently needed for people with schizophrenia. Xanomeline is a dual M1 and M4-preferring muscarinic receptor agonist that does not block D2 dopamine receptors, unlike all currently approved treatments for schizophrenia. Xanomeline-trospium (KarXT) combines xanomeline with the peripherally restricted muscarinic receptor antagonist trospium chloride with the goal of ameliorating xanomeline-related adverse events associated with peripheral muscarinic receptors. The EMERGENT-2 trial aimed to assess the efficacy and safety of KarXT in people with schizophrenia experiencing acute psychosis. Methods: EMERGENT-2 was a randomised, double-blind, placebo-controlled, flexible-dose, 5-week, inpatient, phase 3 trial in people with schizophrenia. Participants were adults aged 18-65 years with a diagnosis of schizophrenia who had a recent worsening of psychosis warranting hospital admission, a Positive and Negative Syndrome Scale (PANSS) score of 80 or higher, and a Clinical Global Impression-Severity score of 4 or higher. The participants were recruited from 22 inpatient sites in the USA, and were randomly assigned (1:1) to KarXT or placebo twice per day. Participants randomly assigned to KarXT received 50 mg xanomeline and 20 mg trospium twice per day for the first 2 days and then 100 mg xanomeline and 20 mg trospium twice per day for days 3-7. Beginning on day 8, KarXT dosing was flexible with an optional increase to 125 mg xanomeline and 30 mg trospium twice per day and the option to return to 100 mg xanomeline and 20 mg trospium based on tolerability. The primary endpoint was change from baseline to week 5 in PANSS total score. Efficacy analyses used the modified intention-to-treat population (all randomly assigned participants who received at least one trial medication dose and had at least one post-baseline PANSS assessment). Least squares mean change from baseline, SE, and least squares mean difference between the KarXT and placebo groups at week 5, along with the 95% CI and two-sided p values were calculated for the primary and secondary continuous efficacy endpoints. Safety analyses included all participants receiving at least one trial medication dose and used descriptive statistics. This trial is registered with ClinicalTrials.gov (NCT04659161). Findings: From Dec 16, 2020, to April 13, 2022, of 407 people who were screened, 252 participants meeting enrolment criteria were randomly assigned to the KarXT (n=126) or placebo (n=126). Baseline PANSS total scores were 98·3 (KarXT; n=126) and 97·9 (placebo; n=125). The trial met the primary endpoint with a mean change from baseline to week 5 in PANSS total score that favoured KarXT (-21·2 points, SE 1·7) versus placebo (-11·6 points, 1·6; least squares mean difference -9·6; 95% CI -13·9 to -5·2; p<0·0001, Cohen's d effect size=0·61). All secondary endpoints were also met, and favoured KarXT versus placebo (p<0·05). The most common adverse events with KarXT versus placebo were constipation (27 [21%] vs 13 [10%]), dyspepsia (24 [19%] vs 10 [8%]), headache (17 [14%] vs 15 [12%]), nausea (24 [19%] vs seven [6%]), vomiting (18 [14%] vs one [1%]), hypertension (12 [10%] vs one [1%]), dizziness (11 [9%] vs four [3%]), gastro-oesophageal reflux disease (eight [6%] vs zero [0%]), and diarrhoea (seven [6%] vs four [3%]). Treatment-emergent adverse event rates of extrapyramidal motor symptoms (KarXT, zero [0%] vs placebo, zero [0%]), akathisia (one [1%] vs one [1%]), weight gain (zero [0%] vs one [1%]), and somnolence (six [5%] vs five [4%]) were similar between the KarXT and placebo groups, as were adverse event-related discontinuation rates (nine [7%] vs seven [6%]). Interpretation: In the EMERGENT-2 trial, KarXT was effective in reducing positive and negative symptoms and was generally well tolerated. These results support the potential for KarXT to represent a new class of effective and well tolerated antipsychotic medicines based on activating muscarinic receptors, not the D2 dopamine receptor-blocking mechanism of all current antipsychotic medications. Results from additional trials, including the identical EMERGENT-3 trial and the 52-week, open-label EMERGENT-4 and EMERGENT-5 trials, will provide additional information on the efficacy and safety of KarXT in people with schizophrenia. Funding: Karuna Therapeutics.

Lancet (London, England) · randomised controlled trial · 144 citationsread the source →

A 12-week double-blind, placebo-controlled study of bupropion sr added to high-dose dual nicotine replacement therapy for smoking cessation or reduction in schizophrenia.

The objective of this study was to examine whether there is a benefit of adding bupropion SR to high-dose combination nicotine replacement therapy (NRT) and weekly group cognitive behavioral therapy (CBT) for smoking reduction or cessation in schizophrenia. Fifty-one adult smokers with schizophrenia were randomly assigned to a 12-week trial of bupropion SR 300 mg/d or placebo added to transdermal nicotine patch, nicotine polacrilex gum, and CBT. The treatment goal was smoking cessation. The primary outcome measure was biochemically confirmed 7-day point-prevalence of 50% to 100% smoking reduction at week 12. Secondary outcomes were biochemically confirmed tobacco abstinence and change from baseline in expired air carbon monoxide (CO) and psychiatric symptoms. Subjects on bupropion + NRT had a greater rate of 50% to 100% smoking reduction at weeks 12 (60% vs. 31%; P = 0.036) and 24, a lower expired air CO in the treatment and follow-up periods, (F = 13.8; P < 0.001) and a greater continuous abstinence rate at week 8, before NRT taper, (52% vs. 19%; P = 0.014). However, relapse rates in subjects on bupropion + dual NRT were 31% during NRT taper (weeks 8-12) and 77% at the 12-month follow-up. Abstinence rates did not differ by treatment group at weeks 12 (36% vs. 19%), 24 (20% vs. 8%), or 52 (12% vs. 8%). Because abstinence rates were high during treatment with combination pharmacotherapy and relapse rates were very high during taper and after discontinuation of treatment, study of longer term treatment with combination pharmacotherapy and CBT for sustained abstinence is warranted in those who attain initial abstinence with this intervention.

Journal of clinical psychopharmacology · randomised controlled trial · 112 citationsread the source →

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

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

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

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

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

Nutrition journal · systematic review · 103 citationsread the source →

Physical activity for women with breast cancer after adjuvant therapy.

Background: Women with a diagnosis of breast cancer may experience short- and long-term disease and treatment-related adverse physiological and psychosocial outcomes. These outcomes can negatively impact prognosis, health-related quality of life (HRQoL), and psychosocial and physical function. Physical activity may help to improve prognosis and may alleviate the adverse effects of adjuvant therapy. Objectives: To assess effects of physical activity interventions after adjuvant therapy for women with breast cancer. Search methods: We searched the Cochrane Breast Cancer Group (CBCG) Specialised Registry, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Physiotherapy Evidence Database (PEDro), SPORTDiscus, PsycINFO, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform, on 18 September 2015. We also searched OpenGrey and Healthcare Management Information Consortium databases. Selection criteria: We searched for randomised and quasi-randomised trials comparing physical activity interventions versus control (e.g. usual or standard care, no physical activity, no exercise, attention control, placebo) after adjuvant therapy (i.e. after completion of chemotherapy and/or radiation therapy, but not hormone therapy) in women with breast cancer. Data collection and analysis: Two review authors independently selected studies, assessed risk of bias, and extracted data. We contacted trial authors to ask for additional information when needed. We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome and used GRADE to assess the quality of evidence for the most important outcomes. Main results: We included 63 trials that randomised 5761 women to a physical activity intervention (n = 3239) or to a control (n = 2524). The duration of interventions ranged from 4 to 24 months, with most lasting 8 or 12 weeks (37 studies). Twenty-eight studies included aerobic exercise only, 21 involved aerobic exercise and resistance training, and seven used resistance training only. Thirty studies described the comparison group as usual or standard care, no intervention, or control. One-fifth of studies reported at least 20% intervention attrition and the average physical activity adherence was approximately 77%.No data were available on effects of physical activity on breast cancer-related and all-cause mortality, or on breast cancer recurrence. Analysis of immediately postintervention follow-up values and change from baseline to end of intervention scores revealed that physical activity interventions resulted in significant small-to-moderate improvements in HRQoL (standardised mean difference (SMD) 0.39, 95% CI 0.21 to 0.57, 22 studies, 1996 women; SMD 0.78, 95% CI 0.39 to 1.17, 14 studies, 1459 women, respectively; low-quality evidence), emotional function (SMD 0.21, 95% CI 0.10 to 0.32, 26 studies, 2102 women, moderate-quality evidence; SMD 0.31, 95% CI 0.09 to 0.53, 15 studies, 1579 women, respectively; low-quality evidence), perceived physical function (SMD 0.33, 95% CI 0.18 to 0.49, 25 studies, 2129 women; SMD 0.60, 95% CI 0.23 to 0.97, 13 studies, 1433 women, respectively; moderate-quality evidence), anxiety (SMD -0.57, 95% CI -0.95 to -0.19, 7 studies, 326 women; SMD -0.37, 95% CI -0.63 to -0.12, 4 studies, 235 women, respectively; low-quality evidence), and cardiorespiratory fitness (SMD 0.44, 95% CI 0.30 to 0.58, 23 studies, 1265 women, moderate-quality evidence; SMD 0.83, 95% CI 0.40 to 1.27, 9 studies, 863 women, respectively; very low-quality evidence).Investigators reported few minor adverse events. Small improvements in physical activity interventions were sustained for three months or longer postintervention in fatigue (SMD -0.43, 95% CI -0.60 to -0.26; SMD -0.47, 95% CI -0.84 to -0.11, respectively), cardiorespiratory fitness (SMD 0.36, 95% CI 0.03 to 0.69; SMD 0.42, 95% CI 0.05 to 0.79, respectively), and self-reported physical activity (SMD 0.44, 95% CI 0.17 to 0.72; SMD 0.51, 95% CI 0.08 to 0.93, respectively) for both follow-up values and change from baseline scores. However, evidence of heterogeneity across trials was due to variation in intervention components (i.e. mode, frequency, intensity, duration of intervention and sessions) and measures used to assess outcomes. All trials reviewed were at high risk of performance bias, and most were also at high risk of detection, attrition, and selection bias. In light of the aforementioned issues, we determined that the evidence was of very low, low, or moderate quality. Authors' conclusions: No conclusions regarding breast cancer-related and all-cause mortality or breast cancer recurrence were possible. However, physical activity interventions may have small-to-moderate beneficial effects on HRQoL, and on emotional or perceived physical and social function, anxiety, cardiorespiratory fitness, and self-reported and objectively measured physical activity. The positive results reported in the current review must be interpreted cautiously owing to very low-to-moderate quality of evidence, heterogeneity of interventions and outcome measures, imprecision of some estimates, and risk of bias in many trials. Future studies with low risk of bias are required to determine the optimal combination of physical activity modes, frequencies, intensities, and durations needed to improve specific outcomes among women who have undergone adjuvant therapy.

The Cochrane database of systematic reviews · meta-analysis · 165 citationsread the source →

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

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

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

Long-term benefits of digital cognitive behavioural therapy for insomnia: Follow-up report from a randomized clinical trial.

Digital cognitive behavioural therapy (dCBT) is an effective treatment for chronic insomnia and also improves well-being and quality of life (QoL). We assessed whether these benefits are sustained and if the effects of dCBT extend to the use of sleep medication and healthcare. In total 1,711 adults (48.0 ± 13.8 years, 77.6% female) with complaints of chronic insomnia participated in a previously published randomized controlled trial (ISRCTN 60530898) comparing dCBT (n = 853) with sleep hygiene education (SHE, n = 858). At weeks 0, 4, 8, 24, 36 and 48, we assessed functional health (Patient-Reported Outcomes Measurement Information System: Global Health Scale); psychological well-being (Warwick-Edinburgh Mental Well-being Scale) and sleep-related QoL (Glasgow Sleep Impact Index), prescribed and non-prescribed sleep medication use, and healthcare utilization. At week 25, those who received SHE at baseline were offered dCBT. dCBT improved functional health (difference: 2.45, 95% confidence interval [CI]: 2.03; 2.88, Cohen's d: 0.50, p < .001), psychological well-being (difference: 4.34, 95% CI: 3.70; 4.98, Cohen's d: 0.55, p < .001) and sleep-related QoL (difference: -44.61, 95%CI: -47.17; -42.05, Cohen's d: -1.44, p < .001) at week 48 compared to baseline. At week 24 dCBT, compared to SHE, also reduced use of prescription and non-prescription sleep medication up to week 24 (adjusted rate ratio [RR]: 0.64, 95% CI: 0.42; 0.97, p = .037 and adjusted RR: 0.52, 95% CI: 0.37; 0.74, p < .0001, respectively), but not healthcare utilization. Uncontrolled follow-up suggests that these effects were sustained for non-prescribed sleep medication (RR: 0.52, 95% CI: 0.40; 0.67, p < .001). In conclusion, this study suggests that dCBT results in sustained benefits to insomnia and its daytime outcomes.

Journal of sleep research · randomised controlled trial · 24 citationsread the source →

Diet and exercise in uterine cancer survivors (DEUS pilot) - piloting a healthy eating and physical activity program: study protocol for a randomized controlled trial.

Background: Endometrial cancer survivors comprise a high-risk group for obesity-related comorbidities. Healthy eating and physical activity can lead to better health and well-being, but this population may experience difficulties adopting healthy lifestyle practices. Personalised behaviour change programmes that are feasible, acceptable and cost-effective are needed. The aim of this trial is to pilot a manualised programme about healthy eating and physical activity. Methods/design: This is a phase II, individually randomized, parallel, controlled, two-site, pilot clinical trial. Adult endometrial cancer survivors (n = 64) who have been diagnosed with endometrial cancer within the previous 3 years and are not on active treatment will be invited to participate. Participants will be assigned in a 1:1 ratio through minimisation to either an 8-week, group-based, behaviour-change programme with weekly 90-min sessions about healthy eating and physical activity or usual care. The intervention will focus on self-monitoring, goal setting and self-rewards. Follow-up assessments will be conducted at 8 and 24 weeks from the baseline assessment. Primary feasibility outcomes will include rates of recruitment, adherence, and retention. Discussion: The study results will inform the development of a definitive randomised controlled trial to test if the programme can improve the health and quality of life of this population. It will also provide guidance on costing the intervention and the health care resource use in this population. Trial registration: ClinicalTrials.gov identifier: NCT02433080, 20 April 2015.

Trials · randomised controlled trial · 14 citationsread the source →

A lay navigator-led, early palliative care intervention for African American and rural family caregivers of individuals with advanced cancer (Project Cornerstone): Results of a pilot randomized trial.

Background: The objective of this study was to assess the feasibility, acceptability, and potential efficacy of ENABLE (Educate, Nurture, Advise, Before Life Ends) Cornerstone-a lay navigator-led, early palliative care telehealth intervention for African American/Black and/or rural-dwelling family caregivers of individuals with advanced cancer (ClinicalTrials.gov identifier NCT03464188). Methods: This was a pilot randomized trial (November 2019 to March 2021). Family caregivers of patients with newly diagnosed, stage III/IV, solid-tumor cancers were randomized to receive either an intervention or usual care. Intervention caregivers were paired with a specially trained lay navigator who delivered 6 weekly, 20-minute to 60-minute telehealth coaching sessions plus monthly follow-up for 24 weeks, reviewing skills in stress management, self-care, getting help, staying organized, and future planning. Feasibility was assessed according to the completion of sessions and questionnaires (predefined as a completion rate ≥80%). Acceptability was determined through intervention participants' ratings of their likelihood of recommending the intervention. Measures of caregiver distress and quality of life were collected at 8 and 24 weeks. Results: Sixty-three family caregivers were randomized (usual care, n = 32; intervention, n = 31). Caregivers completed 65% of intervention sessions and 87% of questionnaires. Average ratings for recommending the program were 9.4, from 1 (not at all likely) to 10 (extremely likely). Over 24 weeks, the mean ± SE Hospital Anxiety and Depression Scale score improved by 0.30 ± 1.44 points in the intervention group and worsened by 1.99 ± 1.39 points in the usual care group (difference, -2.29; Cohen d, -0.32). The mean between-group difference scores in caregiver quality of life was -1.56 (usual care - intervention; d, -0.07). Similar outcome results were observed for patient participants. Conclusions: The authors piloted ENABLE Cornerstone, an intervention for African American and rural-dwelling advanced cancer family caregivers. The acceptability of the intervention and data collection rates were high, and the preliminary efficacy for caregiver distress was promising. Lay summary: To date, very few programs have been developed to support under-resourced cancer family caregivers. To address this need, the authors successfully pilot tested an early palliative care program, called Educate, Nurture, Advise, Before Life Ends (ENABLE) Cornerstone, for African American and rural family caregivers of individuals with advanced cancer. Cornerstone is led by specially trained lay people and involves a series of weekly phone sessions focused on coaching caregivers to manage stress and provide effective support to patients with cancer. The authors are now testing Cornerstone in a larger trial. If the program demonstrates benefit, it may yield a model of caregiver support that could be widely implemented.

Cancer · randomised controlled trial · 47 citationsread the source →

Dialectical behavior therapy for high suicide risk in individuals with borderline personality disorder: a randomized clinical trial and component analysis.

Importance: Dialectical behavior therapy (DBT) is an empirically supported treatment for suicidal individuals. However, DBT consists of multiple components, including individual therapy, skills training, telephone coaching, and a therapist consultation team, and little is known about which components are needed to achieve positive outcomes. Objective: To evaluate the importance of the skills training component of DBT by comparing skills training plus case management (DBT-S), DBT individual therapy plus activities group (DBT-I), and standard DBT which includes skills training and individual therapy. Design, setting, and participants: We performed a single-blind randomized clinical trial from April 24, 2004, through January 26, 2010, involving 1 year of treatment and 1 year of follow-up. Participants included 99 women (mean age, 30.3 years; 69 [71%] white) with borderline personality disorder who had at least 2 suicide attempts and/or nonsuicidal self-injury (NSSI) acts in the last 5 years, an NSSI act or suicide attempt in the 8 weeks before screening, and a suicide attempt in the past year. We used an adaptive randomization procedure to assign participants to each condition. Treatment was delivered from June 3, 2004, through September 29, 2008, in a university-affiliated clinic and community settings by therapists or case managers. Outcomes were evaluated quarterly by blinded assessors. We hypothesized that standard DBT would outperform DBT-S and DBT-I. Interventions: The study compared standard DBT, DBT-S, and DBT-I. Treatment dose was controlled across conditions, and all treatment providers used the DBT suicide risk assessment and management protocol. Main outcomes and measures: Frequency and severity of suicide attempts and NSSI episodes. Results: All treatment conditions resulted in similar improvements in the frequency and severity of suicide attempts, suicide ideation, use of crisis services due to suicidality, and reasons for living. Compared with the DBT-I group, interventions that included skills training resulted in greater improvements in the frequency of NSSI acts (F1,85 = 59.1 [P < .001] for standard DBT and F1,85 = 56.3 [P < .001] for DBT-S) and depression (t399 = 1.8 [P = .03] for standard DBT and t399 = 2.9 [P = .004] for DBT-S) during the treatment year. In addition, anxiety significantly improved during the treatment year in standard DBT (t94 = -3.5 [P < .001]) and DBT-S (t94 = -2.6 [P = .01]), but not in DBT-I. Compared with the DBT-I group, the standard DBT group had lower dropout rates from treatment (8 patients [24%] vs 16 patients [48%] [P = .04]), and patients were less likely to use crisis services in follow-up (ED visits, 1 [3%] vs 3 [13%] [P = .02]; psychiatric hospitalizations, 1 [3%] vs 3 [13%] [P = .03]). Conclusions and relevance: A variety of DBT interventions with therapists trained in the DBT suicide risk assessment and management protocol are effective for reducing suicide attempts and NSSI episodes. Interventions that include DBT skills training are more effective than DBT without skills training, and standard DBT may be superior in some areas. Trial registration: clinicaltrials.gov Identifier: NCT00183651.

JAMA psychiatry · randomised controlled trial · 325 citationsread the source →

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

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

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

Digital smartphone intervention to recognise and manage early warning signs in schizophrenia to prevent relapse: the EMPOWER feasibility cluster RCT.

Background: Relapse is a major determinant of outcome for people with a diagnosis of schizophrenia. Early warning signs frequently precede relapse. A recent Cochrane Review found low-quality evidence to suggest a positive effect of early warning signs interventions on hospitalisation and relapse. Objective: How feasible is a study to investigate the clinical effectiveness and cost-effectiveness of a digital intervention to recognise and promptly manage early warning signs of relapse in schizophrenia with the aim of preventing relapse? Design: A multicentre, two-arm, parallel-group cluster randomised controlled trial involving eight community mental health services, with 12-month follow-up. Settings: Glasgow, UK, and Melbourne, Australia. Participants: Service users were aged > 16 years and had a schizophrenia spectrum disorder with evidence of a relapse within the previous 2 years. Carers were eligible for inclusion if they were nominated by an eligible service user. Interventions: The Early signs Monitoring to Prevent relapse in psychosis and prOmote Wellbeing, Engagement, and Recovery (EMPOWER) intervention was designed to enable participants to monitor changes in their well-being daily using a mobile phone, blended with peer support. Clinical triage of changes in well-being that were suggestive of early signs of relapse was enabled through an algorithm that triggered a check-in prompt that informed a relapse prevention pathway, if warranted. Main outcome measures: The main outcomes were feasibility of the trial and feasibility, acceptability and usability of the intervention, as well as safety and performance. Candidate co-primary outcomes were relapse and fear of relapse. Results: We recruited 86 service users, of whom 73 were randomised (42 to EMPOWER and 31 to treatment as usual). Primary outcome data were collected for 84% of participants at 12 months. Feasibility data for people using the smartphone application (app) suggested that the app was easy to use and had a positive impact on motivations and intentions in relation to mental health. Actual app usage was high, with 91% of users who completed the baseline period meeting our a priori criterion of acceptable engagement (> 33%). The median time to discontinuation of > 33% app usage was 32 weeks (95% confidence interval 14 weeks to ∞). There were 8 out of 33 (24%) relapses in the EMPOWER arm and 13 out of 28 (46%) in the treatment-as-usual arm. Fewer participants in the EMPOWER arm had a relapse (relative risk 0.50, 95% confidence interval 0.26 to 0.98), and time to first relapse (hazard ratio 0.32, 95% confidence interval 0.14 to 0.74) was longer in the EMPOWER arm than in the treatment-as-usual group. At 12 months, EMPOWER participants were less fearful of having a relapse than those in the treatment-as-usual arm (mean difference -4.29, 95% confidence interval -7.29 to -1.28). EMPOWER was more costly and more effective, resulting in an incremental cost-effectiveness ratio of £3041. This incremental cost-effectiveness ratio would be considered cost-effective when using the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year gained. Limitations: This was a feasibility study and the outcomes detected cannot be taken as evidence of efficacy or effectiveness. Conclusions: A trial of digital technology to monitor early warning signs that blended with peer support and clinical triage to detect and prevent relapse is feasible. Future work: A main trial with a sample size of 500 (assuming 90% power and 20% dropout) would detect a clinically meaningful reduction in relapse (relative risk 0.7) and improvement in other variables (effect sizes 0.3-0.4). Trial registration: This trial is registered as ISRCTN99559262. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 27. See the NIHR Journals Library website for further project information. Funding in Australia was provided by the National Health and Medical Research Council (APP1095879).

Health technology assessment (Winchester, England) · randomised controlled trial · 24 citationsread the source →

A Dating Violence Prevention Program for Middle School Youth: A Cluster Randomized Trial.

Objectives: We conducted a cluster randomized controlled trial to test the a priori hypothesis that students attending an intervention middle school would be less likely to report physical adolescent relationship abuse (ARA) 1 year later compared with students attending a control school. Secondary objectives were to determine if the intervention reduced substance misuse, bullying, and fighting. Methods: Twenty-four Texas public middle schools were matched by the size of student enrollment, number of economically disadvantaged students, and race and ethnicity of the student body and randomly assigned to the intervention (n = 12; 1237 participants) or the control (n = 12; 1531participants) group. The intervention, Fourth R, is a classroom-based curriculum delivered by existing teachers and consists of 21 lessons on injury prevention, substance use, and growth and development. Results: Participants (50% female) self-reported ethnicity as Hispanic or Latinx (35%), Black or African American (24%), Asian American (17%), White (8%), and multiethnicity or other (16%). Among those who have dated, students in the intervention schools were less likely to report perpetrating physical ARA (intervention = 14.9% versus control = 18.3%) relative to students in the control schools (adjusted odds ratio, 0.66; 95% confidence interval, 0.43-1.00; P = .05). In the overall sample, no significant differences emerged between control and intervention groups with respect to substance misuse, fighting, and bullying. Conclusions: The middle school version of Fourth R is effective in reducing physical ARA perpetration over at least 1 year. The intervention did not have an effect on bullying perpetration, physical fighting with peers, and substance misuse. Long-term assessment, especially follow-up that covers the transition to high school, is needed to examine the program benefit on key outcomes.

Pediatrics · randomised controlled trial · 19 citationsread the source →

Use of the PREPARE (PREhabilitation, Physical Activity and exeRcisE) program to improve outcomes after lumbar fusion surgery for severe low back pain: a study protocol of a person-centred randomised controlled trial.

Background: Following lumbar fusion surgery, a successful outcome is empirically linked to effective rehabilitation. While rehabilitation is typically postoperative, the phase before surgery - termed prehabilitation - is reportedly an ideal time to prepare the patient. There are presently no guidelines for prehabilitation before lumbar fusion surgery. Physical activity has well-known health benefits, and staying physically active despite pain is a major principle in non-pharmacological chronic low back pain treatment. Psychological factors such as fear of movement, pain catastrophizing and low self-efficacy are known to be barriers to staying active. No studies have investigated prehabilitation protocols that promote physical activity and target psychological risk factors before lumbar fusion surgery. The aim of our proposed randomised controlled trial is to investigate whether patients who undergo lumbar fusion surgery for degenerative disc disease experience better functioning with a physiotherapeutic prehabilitation program (PREPARE) based on a cognitive behavioural approach compared to conventional care. Methods/design: We will recruit 110 patients between 18-70 years of age with degenerative disc disease who are waiting for lumbar fusion surgery. These patients will be randomly assigned to receive either PREPARE or conventional care. PREPARE uses a person-centred perspective and focuses on promoting physical activity and targeting psychological risk factors before surgery. The primary outcome will be disability measured using the Oswestry Disability Index 2.0. Secondary outcomes will include functioning (patient-reported and performance-based), physical activity (accelerometer), health-related quality of life, back and leg pain intensity, pain catastrophizing, kinesiophobia, self-efficacy, depression, anxiety, satisfaction with treatment results and health economic factors. Data will be collected at baseline (preoperatively) after the intervention (preoperatively), 3 and 8 weeks, 3, 6, 12, 24 and 60 months postoperatively. Discussion: We hypothesise that the focus on promoting physical activity and targeting psychological risk factors before surgery will decrease disability and help the patients to be more active despite pain both before and after surgery. We will use a combination of outcome measures both patient-reported and performance-based, as well as accelerometer data. This will provide a more comprehensive picture of the patient's functioning than just patient-reported outcomes alone. Trial registration: Current Controlled Trials ISCRTN17115599 , Retrospectively Registered 18 May 2015.

BMC musculoskeletal disorders · randomised controlled trial · 26 citationsread the source →

Outreach for chlamydia and gonorrhoea screening: a systematic review of strategies and outcomes.

Background: High Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) prevalence have been reported in populations that do not regularly access health centres for sexually transmissible infections (STI) testing. We reviewed current outreach strategies used to increase access to STI testing and their outcomes. Methods: We systematically reviewed the literature for English language studies published between 1 January 2005 and 28 January 2011 describing CT and/or NG screening programs in non-clinical outreach settings. Results: We identified 25 programs, with the majority occurring in either Australia (32%) or the United States (32%). The most common target groups were young people aged 15-29 years (52%), men who have sex with men (24%) and sex workers (8%). The median CT positivity was 7.7% (Inter Quartile Range [IQR]: 3.0%-11.1%, n=19 programs), and median NG positivity was 2.6% (IQR: 0.0%-8.0%, n=10). The median participation rate was 53% (IQR: 23.9%-81.3%), and a median of 79.6% (IQR: 55.1%-89.4%) of participants were tested, with a median of 100 tests conducted per program (IQR: 65-331, range: 11-1808). Across all settings the participation rate was highest among target groups gathering in community service venues (community centres, parenting centres, homeless shelters) (median=81.4%, n=4), and social venues (sporting venues or bars) (80.4%, n=1). Lower participation rates were found in street/public community areas (median=23.9%, n=3) and sex on premises venues (10.4% and 24.3%, n=2). Conclusions: The review indicated that although CT and NG outreach programs reached a relatively small number of people the yield of infections is high. Settings which appear to be more effective at encouraging participation appear to be those within an existing venue, rather than in public areas.

BMC public health · systematic review · 32 citationsread the source →

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

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

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

Exercise for women receiving adjuvant therapy for breast cancer.

Background: A huge clinical research database on adjuvant cancer treatment has verified improvements in breast cancer outcomes such as recurrence and mortality rates. On the other hand, adjuvant and neoadjuvant therapy with chemotherapy and radiotherapy impacts on quality of life due to substantial short- and long-term side effects. A number of studies have evaluated the effect of exercise interventions on those side effects. This is an updated version of the original Cochrane review published in 2006. The original review identified some benefits of physical activity on physical fitness and the resulting capacity for performing activities of daily life. It also identified a lack of evidence for other outcomes, providing clear justification for an updated review. Objectives: To assess the effect of aerobic or resistance exercise interventions during adjuvant treatment for breast cancer on treatment-related side effects such as physical deterioration, fatigue, diminished quality of life, depression, and cognitive dysfunction. Search methods: We carried out an updated search in the Cochrane Breast Cancer Group Specialised Register (30 March 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2015), MEDLINE (1966 to 30 March 2015), and EMBASE (1966 to 30 March 2015). We did not update the original searches in CINAHL (1982 to 2004), SPORTDiscus (1975 to 2004), PsycINFO (1872 to 2003), SIGLE (1880 to 2004), and ProQuest Digital Dissertations (1861 to 2004). We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov for ongoing trials on 30 March 2015. We screened references in relevant reviews and published clinical trials. Selection criteria: We included randomised controlled trials that examined aerobic or resistance exercise or both in women undergoing adjuvant treatment for breast cancer. Published and unpublished trials were eligible. Data collection and analysis: Two review authors independently performed data extraction, assessed trials, and graded the methodological quality using Cochrane's 'Risk of bias' tool. Any disagreements were resolved through discussion or by consulting the third review author. We entered data into Review Manager for analysis. For outcomes assessed with a variety of instruments, we used the standardised mean difference (SMD) as a summary statistic for meta-analysis; for those assessed with the same instrument, we used the mean difference (MD). Main results: For this 2015 update we included a total of 32 studies with 2626 randomised women, 8 studies from the original search and 24 studies from the updated search. We found evidence that physical exercise during adjuvant treatment for breast cancer probably improves physical fitness (SMD 0.42, 95% confidence interval (CI) 0.25 to 0.59; 15 studies; 1310 women; moderate-quality evidence) and slightly reduces fatigue (SMD -0.28, 95% CI -0.41 to -0.16; 19 studies; 1698 women; moderate-quality evidence). Exercise may lead to little or no improvement in health-related quality of life (MD 1.10, 95% CI -5.28 to 7.48; 1 study; 68 women; low-quality evidence), a slight improvement in cancer site-specific quality of life (MD 4.24, 95% CI -1.81 to 10.29; 4 studies; 262 women; low-quality evidence), and an improvement in cognitive function (MD -11.55, 95% CI -22.06 to -1.05; 2 studies; 213 women; low-quality evidence). Exercise probably leads to little or no difference in cancer-specific quality of life (SMD 0.12, 95% CI 0.00 to 0.25; 12 studies; 1012 women; moderate-quality evidence) and little or no difference in depression (SMD -0.15, 95% CI -0.30 to 0.01; 5 studies; 674 women; moderate-quality evidence). Evidence for other outcomes ranged from low to moderate quality. Seven trials reported a very small number of adverse events. Authors' conclusions: Exercise during adjuvant treatment for breast cancer can be regarded as a supportive self care intervention that probably results in less fatigue, improved physical fitness, and little or no difference in cancer-specific quality of life and depression. Exercise may also slightly improve cancer site-specific quality of life and cognitive function, while it may result in little or no difference in health-related quality of life. This review is based on trials with a considerable degree of clinical heterogeneity regarding adjuvant cancer treatments and exercise interventions. Due to the difficulty of blinding exercise trials, all included trials were at high risk for performance bias. Furthermore, the majority of trials were at high risk for detection bias, largely due to most outcomes being self reported. The findings of the updated review have enabled us to make a more precise conclusion that both aerobic and resistance exercise can be regarded as beneficial for individuals with adjuvant therapy-related side effects. Further research is required to determine the optimal type, intensity, and timing of an exercise intervention. Furthermore, long-term evaluation is required due to possible long-term side effects of adjuvant treatment.

The Cochrane database of systematic reviews · meta-analysis · 188 citationsread the source →

Hippocampal N-acetylaspartate concentration and response to riluzole in generalized anxiety disorder.

Background: Previous research has suggested the therapeutic potential of glutamate-modulating agents for severe mood and anxiety disorders, potentially resulting from enhancement of neuroplasticity. We used proton magnetic resonance spectroscopic imaging ((1)H MRSI) to examine the acute and chronic effects of the glutamate-release inhibitor riluzole on hippocampal N-acetylaspartate (NAA), a neuronal marker, in patients with generalized anxiety disorder (GAD) and examined the relationship between changes in NAA and clinical outcome. Methods: Fourteen medication-free GAD patients were administered open-label riluzole and then evaluated by (1)H MRSI before drug administration, and 24 hours and 8 weeks following treatment. Patients were identified as responders (n = 9) or nonresponders (n = 5). Seven untreated, medically healthy volunteers, comparable in age, sex, IQ, and body mass index to the patients, received scans at the same time intervals. Molar NAA concentrations in bilateral hippocampus, and change in anxiety ratings were the primary outcome measures. Results: A group-by-time interaction was found, with riluzole responders showing mean increases in hippocampal NAA across the three time points, whereas nonresponders had decreases over time. In GAD patients at Week 8, hippocampal NAA concentration and proportional increase in NAA from baseline both were positively associated with improvements in worry and clinician-rated anxiety. Conclusions: These preliminary data support a specific association between hippocampal NAA and symptom alleviation following riluzole treatment in GAD. Placebo-controlled investigations that examine hippocampal NAA as a viable surrogate endpoint for clinical trials of neuroprotective and plasticity-enhancing agents are warranted.

Biological psychiatry · randomised controlled trial · 49 citationsread the source →

Stepped care for depression and anxiety: from primary care to specialized mental health care: a randomised controlled trial testing the effectiveness of a stepped care program among primary care patients with mood or anxiety disorders.

Background: Mood and anxiety disorders are highly prevalent and have a large impact on the lives of the affected individuals. Therefore, optimal treatment of these disorders is highly important. In this study we will examine the effectiveness of a stepped care program for primary care patients with mood and anxiety disorders. A stepped care program is characterized by different treatment steps that are arranged in order of increasing intensity. Methods: This study is a randomised controlled trial with two conditions: stepped care and care as usual, whereby the latter forms the control group. The stepped care program consists of four evidence based interventions: (1) Watchful waiting, (2) Guided self-help, (3) Problem Solving Treatment and (4) Medication and/or specialized mental health care. The study population consists of primary care attendees aged 18-65 years. Screeners are sent to all patients of the participating general practitioners. Individuals with a Diagnostic and Statistical Manual of mental disorders (DSM) diagnosis of major depression, dysthymia, panic disorder (with or without agoraphobia), generalized anxiety disorder, or social phobia are included as well as individuals with minor depression and anxiety disorders. Primary focus is the reduction of depressive and anxiety symptoms. Both conditions are monitored at 8, 16 and 24 weeks. Discussion: This study evaluates the effectiveness of a stepped care program for patients with depressive and anxiety disorder. If effective, a stepped care program can form a worthwhile alternative for care as usual. Strengths and limitations of this study are discussed. Trial registration: Current Controlled Trails: ISRCTN17831610.

BMC health services research · randomised controlled trial · 26 citationsread the source →

Stepped care treatment for depression and anxiety in primary care. a randomized controlled trial.

Background: Depressive and anxiety disorders are common in general practice but not always treated adequately. Introducing stepped care might improve this. In this randomized trial we examined the effectiveness of such a stepped care model. Methods: The study population consisted of primary care attendees aged 18-65 years with minor or major DSM-IV depressive and/or anxiety disorders, recruited through screening. We randomized 120 patients to either stepped care or care as usual. The stepped care program consisted of (1) watchful waiting, (2) guided self-help, (3) short face-to-face problem solving treatment and (4) pharmacotherapy and/or specialized mental health care. Patients were assessed at baseline and after 8, 16 and 24 weeks. Results: Symptoms of depression and anxiety decreased significantly over time for both groups. However, there was no statistically significant difference between the two groups (IDS: P = 0.35 and HADS: P = 0.64). The largest, but not significant, effect (d = -0.21) was found for anxiety on T3. In both groups approximately 48% of the patients were recovered from their DSM-IV diagnosis at the final 6 months assessment. Conclusions: In summary we could not demonstrate that stepped care for depression and anxiety in general practice was more effective than care as usual. Possible reasons are discussed. Trial registration: Current Controlled Trails: ISRCTN17831610.

Trials · randomised controlled trial · 46 citationsread the source →

Zinc for attention-deficit/hyperactivity disorder: placebo-controlled double-blind pilot trial alone and combined with amphetamine.

Objective: To explore effects of zinc supplementation in American children with attention-deficit/hyperactivity disorder (ADHD). Mideastern trials reported significant benefit from 13-40 mg elemental zinc as the sulfate. Method: We randomly assigned 52 children aged 6-14 with DSM-IV ADHD to zinc supplementation (15 mg every morning [qAM] or two times per day [b.i.d.] as glycinate, n = 28) or matched placebo (n = 24) for 13 weeks: 8 weeks monotherapy and then 5 weeks with added d-amphetamine (AMPH). AMPH dose was weight-standardized for 2 weeks and then clinically optimized by week 13. Zinc glycinate was chosen as having less gastrointestinal discomfort than sulfate. Hypotheses were that zinc would improve inattention more than placebo by effect size of d > 0.25 at 8 weeks; zinc+AMPH would improve ADHD symptoms more than placebo+AMPH by d > 0.25, and optimal dose of AMPH with zinc would be 20% lower than with placebo. An interim analysis requested by the National Institute of Mental Health resulted in an increased dosage, so that 20 received 15 mg/day qAM and 8 received 30 mg/day (15 mg b.i.d.) Results: Only the third hypothesis was upheld: Optimal mg/kg AMPH dose with b.i.d. zinc was 37% lower than with placebo. Other clinical outcomes were equivocal, sometimes favoring zinc, sometimes placebo, but objective neuropsychological measures mostly favored b.i.d. zinc (d = 0.36-0.7). Safety tests and adverse events were not different between groups. Copper and iron blood indices were not impaired by 8 weeks of 30 mg/day zinc. Conclusion: Doses up to 30 mg/day of zinc were safe for at least 8 weeks, but clinical effect was equivocal except for 37% reduction in amphetamine optimal dose with 30 mg/day zinc (not with 15 mg). Possible reasons for difference from mideastern reports include endemic diets, population genetics, relative rate of zinc deficiency, difference in background nutrition, insufficient dosage or absorption, or wrong anion (sulfate may be necessary for reported benefit). Dose may be especially important: All visually impressive advantages over placebo appeared only with 15 mg b.i.d. rather than once a day. Future research should use larger doses than 15 mg/day, provide a basic recommended daily allowance/intake multivitamin/mineral supplement for all to standardize background nutrition, select participants for low zinc, and consider the issue of anion interaction.

Journal of child and adolescent psychopharmacology · randomised controlled trial · 59 citationsread the source →

The impact of cash transfers on social determinants of health and health inequalities in sub-Saharan Africa: a systematic review.

Cash transfers (CTs) are now high on the agenda of most governments in low- and middle-income countries. Within the field of health promotion, CTs constitute a healthy public policy initiative as they have the potential to address the social determinants of health (SDoH) and health inequalities. A systematic review was conducted to synthesise the evidence on CTs' impacts on SDoH and health inequalities in sub-Saharan Africa, and to identify the barriers and facilitators of effective CTs. Twenty-one electronic databases and the websites of 14 key organizations were searched in addition to grey literature and hand searching of selected journals for quantitative and qualitative studies on CTs' impacts on SDoH and health outcomes. Out of 182 full texts screened for eligibility, 79 reports that reported findings from 53 studies were included in the final review. The studies were undertaken within 24 CTs comprising 11 unconditional CTs (UCTs), 8 conditional CTs (CCTs) and 5 combined UCTs and CCTs. The review found that CTs can be effective in tackling structural determinants of health such as financial poverty, education, household resilience, child labour, social capital and social cohesion, civic participation, and birth registration. The review further found that CTs modify intermediate determinants such as nutrition, dietary diversity, child deprivation, sexual risk behaviours, teen pregnancy and early marriage. In conjunction with their influence on SDoH, there is moderate evidence from the review that CTs impact on health and quality of life outcomes. The review also found many factors relating to intervention design features, macro-economic stability, household dynamics and community acceptance of programs that could influence the effectiveness of CTs. The external validity of the review findings is strong as the findings are largely consistent with those from Latin America. The findings thus provide useful insights to policy makers and managers and can be used to optimise CTs to reduce health inequalities.

Health policy and planning · systematic review · 88 citationsread the source →

Burden of 375 diseases and injuries, risk-attributable burden of 88 risk factors, and healthy life expectancy in 204 countries and territories, including 660 subnational locations, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023.

Background: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. Methods: The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. Findings: Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant). Interpretation: Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. Funding: Gates Foundation and Bloomberg Philanthropies.

Lancet (London, England) · 257 citationsread the source →

Repetitive task training for improving functional ability after stroke.

Background: Repetitive task training (RTT) involves the active practice of task-specific motor activities and is a component of current therapy approaches in stroke rehabilitation. Objectives: Primary objective: To determine if RTT improves upper limb function/reach and lower limb function/balance in adults after stroke. Secondary objectives: 1) To determine the effect of RTT on secondary outcome measures including activities of daily living, global motor function, quality of life/health status and adverse events. 2) To determine the factors that could influence primary and secondary outcome measures, including the effect of 'dose' of task practice; type of task (whole therapy, mixed or single task); timing of the intervention and type of intervention. Search methods: We searched the Cochrane Stroke Group Trials Register (4 March 2016); the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 5: 1 October 2006 to 24 June 2016); MEDLINE (1 October 2006 to 8 March 2016); Embase (1 October 2006 to 8 March 2016); CINAHL (2006 to 23 June 2016); AMED (2006 to 21 June 2016) and SPORTSDiscus (2006 to 21 June 2016). Selection criteria: Randomised/quasi-randomised trials in adults after stroke, where the intervention was an active motor sequence performed repetitively within a single training session, aimed towards a clear functional goal. Data collection and analysis: Two review authors independently screened abstracts, extracted data and appraised trials. We determined the quality of evidence within each study and outcome group using the Cochrane 'Risk of bias' tool and GRADE (Grades of Recommendation, Assessment, Development and Evaluation) criteria. We did not assess follow-up outcome data using GRADE. We contacted trial authors for additional information. Main results: We included 33 trials with 36 intervention-control pairs and 1853 participants. The risk of bias present in many studies was unclear due to poor reporting; the evidence has therefore been rated 'moderate' or 'low' when using the GRADE system. There is low-quality evidence that RTT improves arm function (standardised mean difference (SMD) 0.25, 95% confidence interval (CI) 0.01 to 0.49; 11 studies, number of participants analysed = 749), hand function (SMD 0.25, 95% CI 0.00 to 0.51; eight studies, number of participants analysed = 619), and lower limb functional measures (SMD 0.29, 95% CI 0.10 to 0.48; five trials, number of participants analysed = 419). There is moderate-quality evidence that RTT improves walking distance (mean difference (MD) 34.80, 95% CI 18.19 to 51.41; nine studies, number of participants analysed = 610) and functional ambulation (SMD 0.35, 95% CI 0.04 to 0.66; eight studies, number of participants analysed = 525). We found significant differences between groups for both upper-limb (SMD 0.92, 95% CI 0.58 to 1.26; three studies, number of participants analysed = 153) and lower-limb (SMD 0.34, 95% CI 0.16 to 0.52; eight studies, number of participants analysed = 471) outcomes up to six months post treatment but not after six months. Effects were not modified by intervention type, dosage of task practice or time since stroke for upper or lower limb. There was insufficient evidence to be certain about the risk of adverse events. Authors' conclusions: There is low- to moderate-quality evidence that RTT improves upper and lower limb function; improvements were sustained up to six months post treatment. Further research should focus on the type and amount of training, including ways of measuring the number of repetitions actually performed by participants. The definition of RTT will need revisiting prior to further updates of this review in order to ensure it remains clinically meaningful and distinguishable from other interventions.

The Cochrane database of systematic reviews · meta-analysis · 242 citationsread the source →

Cognitive behavioural therapy and short-term psychoanalytical psychotherapy versus a brief psychosocial intervention in adolescents with unipolar major depressive disorder (IMPACT): a multicentre, pragmatic, observer-blind, randomised controlled superiority trial.

Background: Psychological treatments for adolescents with unipolar major depressive disorder are associated with diagnostic remission within 28 weeks in 65-70% of patients. We aimed to assess the medium-term effects and costs of psychological therapies on maintenance of reduced depression symptoms 12 months after treatment. Methods: We did this multicentre, pragmatic, observer-blind, randomised controlled superiority trial (IMPACT) at 15 National Health Service child and adolescent mental health service (CAMHS) clinics in three regions in England. Adolescent patients (aged 11-17 years) with a diagnosis of DSM IV major depressive disorder were randomly assigned (1:1:1), via a web-based randomisation service, to receive cognitive behavioural therapy (CBT) or short-term psychoanalytical therapy versus a reference brief psychological intervention. Randomisation was stochastically minimised by age, sex, self-reported depression sum score, and region. Patients and clinicians were aware of group allocation, but allocation was concealed from outcome assessors. Patients were followed up and reassessed at weeks 6, 12, 36, 52, and 86 post-randomisation. The primary outcome was self-reported depression symptoms at weeks 36, 52, and 86, as measured with the self-reported Mood and Feelings Questionnaire (MFQ). Because our aim was to compare the two psychological therapies with the brief psychosocial intervention, we first established whether CBT was inferior to short-term psychoanalytical psychotherapy for the same outcome. Primary analysis was by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN83033550. Findings: Between June 29, 2010, and Jan 17, 2013, we randomly assigned 470 patients to receive the brief psychosocial intervention (n=158), CBT (n=155), or short-term psychoanalytical therapy (n=157); 465 patients comprised the intention-to-treat population. 392 (84%) patients had available data for primary analysis by the end of follow-up. Treatment fidelity and differentiation were established between the three interventions. The median number of treatment sessions differed significantly between patients in the brief psychosocial intervention group (n=6 [IQR 4-11]), CBT group (n=9 [5-14]), and short-term psychoanalytical therapy group (n=11 [5-23]; p<0·0001), but there was no difference between groups in the average duration of treatment (27·5 [SD 21·5], 24·9 [17·7], 27·9 [16·8] weeks, respectively; Kruskal-Wallis p=0·238). Self-reported depression symptoms did not differ significantly between patients given CBT and those given short-term psychoanalytical therapy at weeks 36 (treatment effect 0·179, 95% CI -3·731 to 4·088; p=0·929), 52 (0·307, -3·161 to 3·774; p=0·862), or 86 (0·578, -2·948 to 4·104; p=0·748). These two psychological treatments had no superiority effect compared with brief psychosocial intervention at weeks 36 (treatment effect -3·234, 95% CI -6·611 to 0·143; p=0·061), 52 (-2·806, -5·790 to 0·177; p=0·065), or 86 (-1·898, -4·922 to 1·126; p=0·219). Physical adverse events (self-reported breathing problems, sleep disturbances, drowsiness or tiredness, nausea, sweating, and being restless or overactive) did not differ between the groups. Total costs of the trial interventions did not differ significantly between treatment groups. Interpretation: We found no evidence for the superiority of CBT or short-term psychoanalytical therapy compared with a brief psychosocial intervention in maintenance of reduced depression symptoms 12 months after treatment. Short-term psychoanalytical therapy was as effective as CBT and, together with brief psychosocial intervention, offers additional patient choice for psychological therapy, alongside CBT, for adolescents with moderate to severe depression who are attending routine specialist CAMHS clinics. Funding: National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme, and the Department of Health.

The lancet. Psychiatry · randomised controlled trial · 149 citationsread the source →

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

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

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

Histology, physiology, and glucose and lipid metabolism of Lateolabrax maculatus under low temperature stress.

Spotted sea bass (Lateolabrax maculatus) is a popular and important commercial fish throughout the world, but it is unknown whether introducing domesticated fish to locations that experience cold weather might alter physiological performance. In this study, we evaluated the behavior, fatty acid content, histological analysis of liver and gills, liver enzymatic activity in carbohydrate and lipid metabolism, and gene expression in liver related to carbohydrate and lipid metabolism of spotted sea bass acclimatized at 22 °C (control), 16 °C, 10 °C, 8 °C, and 4 °C for 24 h, and 8 °C for 4 days. When L. maculatus was exposed to acute cold stress for 24 h, the gill showed curling, lamellar disorganization, lamellar epithelium hyperplasia, and formed aneurysms inside of the secondary lamellae. Long term stress over four days resulted in severe lamellar epithelium hyperplasia and curling. Continued extreme cold exposure (4 °C) in L. maculatus caused liver HK, PK levels and LDH activities to achieve a peak value at 0 h, and decreased over time. These indicated that glucose metabolism might play critical roles in the initial time of stress. Results of carbohydrate and lipid metabolism showed that lipids appear to play roles in prolonged cold stress. The constitutive transcriptional levels of six genes related to glucose (G6Pase) and lipid metabolism (PPAR-α, PPAR-γ) and mTOR signal pathway (eif4ebp1, eif4ebp2, mlst8) genes increased significantly in most groups during cold stress.

Journal of thermal biology · 30 citationsread the source →

Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic heart failure.

Aims: In chronic heart failure (CHF), reduced vagal activity correlates with increased mortality and acute decompensation. Experimentally, chronic vagus nerve stimulation (VNS) improved left ventricular (LV) function and survival; clinically, it is used for the treatment of drug-refractory epilepsy. We assessed safety and tolerability of chronic VNS in symptomatic CHF patients, using a novel implantable nerve stimulation system. The secondary goal was to obtain preliminary data on clinical efficacy. Methods and results: This multi-centre, open-label phase II, two-staged study (8-patient feasibility phase plus 24-patient safety and tolerability phase) enrolled 32 New York Heart Association (NYHA) class II-IV patients [age 56 ± 11 years, LV ejection fraction (LVEF) 23 ± 8%]. Right cervical VNS with CardioFit (BioControl Medical) implantable system started 2-4 weeks after implant, slowly raising intensity; patients were followed 3 and 6 months thereafter with optional 1-year follow-up. Overall, 26 serious adverse events (SAEs) occurred in 13 of 32 patients (40.6%), including three deaths and two clearly device-related AEs (post-operative pulmonary oedema, need of surgical revision). Expected non-serious device-related AEs (cough, dysphonia, and stimulation-related pain) occurred early but were reduced and disappeared after stimulation intensity adjustment. There were significant improvements (P < 0.001) in NYHA class quality of life, 6-minute walk test (from 411 ± 76 to 471 ± 111 m), LVEF (from 22 ± 7 to 29 ± 8%), and LV systolic volumes (P = 0.02). These improvements were maintained at 1 year. Conclusions: This open-label study shows that chronic VNS in CHF patients with severe systolic dysfunction may be safe and tolerable and may improve quality of life and LV function. A controlled clinical trial appears warranted.

European heart journal · clinical trial · 373 citationsread the source →

Mindfulness intervention for child abuse survivors.

Twenty-seven adult survivors of childhood sexual abuse participated in a pilot study comprising an 8-week mindfulness meditation-based stress reduction (MBSR) program and daily home practice of mindfulness skills. Three refresher classes were provided through final follow-up at 24 weeks. Assessments of depressive symptoms, post-traumatic stress disorder (PTSD), anxiety, and mindfulness, were conducted at baseline, 4, 8, and 24 weeks. At 8 weeks, depressive symptoms were reduced by 65%. Statistically significant improvements were observed in all outcomes post-MBSR, with effect sizes above 1.0. Improvements were largely sustained until 24 weeks. Of three PTSD symptom criteria, symptoms of avoidance/numbing were most greatly reduced. Compliance to class attendance and home practice was high, with the intervention proving safe and acceptable to participants. These results warrant further investigation of the MBSR approach in a randomized, controlled trial in this patient population.

Journal of clinical psychology · 102 citationsread the source →

End-of-life decisions: a cohort study of the withdrawal of all active treatment in intensive care units in the United Kingdom.

Objective: To describe the epidemiology of active treatment withdrawal in a nationally representative cohort of intensive care units (ICUs) focusing on between-unit differences. Design and setting: Cohort study in 127 adult general ICUs in England, Wales and Northern Ireland, 1995 to 2001. Patients: 118,199 adult admissions to ICUs. Measurements and results: The decision to withdraw all active treatment was made for 11,694 of 118,199 patients (9.9%). There were a total of 36,397 deaths (30.8%) before discharge from hospital, and 11,586 (31.8%) of these occurred after the decision to withdraw active treatment, with no change over time (p=0.54). Considerable variation existed between units regarding the percentage of ICU deaths that occurred after the decision to withdraw active treatment (1.7-96.1%). Median time to death after the decision to withdraw active treatment was 2.4 h; 8% survived more than 24 h. After multilevel modelling, the factors independently associated with the decision to withdraw active treatment were: older age, pre-existing severe medical conditions, emergency surgery or medical admission, cardiopulmonary resuscitation in the 24 h prior to admission, and ventilation or sedation/paralysis in the first 24 h after admission. Substantial between unit variability remained after accounting for case-mix differences in admissions. Conclusions: Although we were unable to examine partial withdrawal or withholding of care in this study, we found that the withdrawal of all active treatment is widespread in ICUs in the United Kingdom. There was little change in this practice over the period examined. However, there was considerable variation by unit, even after accounting for patient factors and differences in size and type of ICU, suggesting improved guidelines may be useful to facilitate uniform decision making.

Intensive care medicine · cohort or longitudinal · 111 citationsread the source →

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

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

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

Nicotine receptor partial agonists for smoking cessation.

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

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

Kangaroo mother care for preterm or low birth weight infants: a systematic review and meta-analysis.

Importance: The Cochrane review (2016) on kangaroo mother care (KMC) demonstrated a significant reduction in the risk of mortality in low birth weight infants. New evidence from large multi-centre randomised trials has been available since its publication. Objective: Our systematic review compared the effects of KMC vs conventional care and early (ie, within 24 hours of birth) vs late initiation of KMC on critical outcomes such as neonatal mortality. Methods: Eight electronic databases, including PubMed®, Embase, and Cochrane CENTRAL, from inception until March 2022, were searched. All randomised trials comparing KMC vs conventional care or early vs late initiation of KMC in low birth weight or preterm infants were included. Data extraction and synthesis: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered with PROSPERO. Main outcomes and measures: The primary outcome was mortality during birth hospitalization or 28 days of life. Other outcomes included severe infection, hypothermia, exclusive breastfeeding rates, and neurodevelopmental impairment. Results were pooled using fixed-effect and random-effects meta-analyses in RevMan 5.4 and Stata 15.1 (StataCorp, College Station, TX). Results: In total, 31 trials with 15 559 infants were included in the review; 27 studies compared KMC with conventional care, while four compared early vs late initiation of KMC. Compared with conventional care, KMC reduces the risks of mortality (relative risk (RR) 0.68; 95% confidence interval (CI) 0.53 to 0.86; 11 trials, 10 505 infants; high certainty evidence) during birth hospitalisation or 28 days of age and probably reduces severe infection until the latest follow-up (RR 0.85, 95% CI 0.79 to 0.92; nine trials; moderate certainty evidence). On subgroup analysis, the reduction in mortality was noted irrespective of gestational age or weight at enrolment, time of initiation, and place of initiation of KMC (hospital or community); the mortality benefits were greater when the daily duration of KMC was at least 8 hours per day than with shorter-duration KMC. Studies comparing early vs late-initiated KMC demonstrated a reduction in neonatal mortality (RR 0.77, 95% CI 0.66 to 0.91; three trials, 3693 infants; high certainty evidence) and a probable decrease in clinical sepsis until 28-days (RR 0.85, 95% CI 0.76 to 0.96; two trials; low certainty evidence) following early initiation of KMC. Conclusions and relevance: The review provides updated evidence on the effects of KMC on mortality and other critical outcomes in preterm and low birth weight infants. The findings suggest that KMC should preferably be initiated within 24 hours of birth and provided for at least 8 hours daily.

BMJ global health · meta-analysis · 90 citationsread the source →

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

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

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

Improvement of Attention-Deficit/Hyperactivity Disorder Symptoms in School-Aged Children, Adolescents, and Young Adults With Autism via a Digital Smartglasses-Based Socioemotional Coaching Aid: Short-Term, Uncontrolled Pilot Study.

Background: People with autism spectrum disorder (ASD) commonly experience symptoms related to attention-deficit/hyperactivity disorder (ADHD), including hyperactivity, inattention, and impulsivity. One-third of ASD cases may be complicated by the presence of ADHD. Individuals with dual diagnoses face greater barriers to accessing treatment for ADHD and respond less positively to primary pharmacologic interventions. Nonpharmacologic technology-aided tools for hyperactivity and inattention in people with ASD are being developed, although research into their efficacy and safety remains limited. Objective: The objective of this preliminary study was to describe the changes in ADHD-related symptoms in children, adolescents, and young adults with ASD immediately after use of the Empowered Brain system, a behavioral and social communication aid for ASD running on augmented reality smartglasses. Methods: We recruited 8 children, adolescents, and young adults with ASD (male to female ratio of 7:1, mean age 15 years, range 11.7-20.5 years) through a Web-based research signup form. The baseline score on the hyperactivity subscale of the Aberrant Behavioral Checklist (ABC-H), a measure of hyperactivity, inattention, and impulsivity, determined their classification into a high ADHD-related symptom group (n=4, ABC-H≥13) and a low ADHD-related symptom group (n=4, ABC-H<13). All participants received an intervention with Empowered Brain, where they used smartglasses-based social communication and behavioral modules while interacting with their caregiver. We then calculated caregiver-reported ABC-H scores at 24 and 48 hours after the session. Results: All 8 participants were able to complete the intervention session. Postintervention ABC-H scores were lower for most participants at 24 hours (n=6, 75%) and for all participants at 48 hours (n=8, 100%). At 24 hours after the session, average participant ABC-H scores decreased by 54.9% in the high ADHD symptom group and by 20% in the low ADHD symptom group. At 48 hours after the session, ABC-H scores compared with baseline decreased by 56.4% in the high ADHD symptom group and by 66.3% in the low ADHD symptom group. Conclusions: This study provides initial evidence for the possible potential of the Empowered Brain system to reduce ADHD-related symptoms, such as hyperactivity, inattention, and impulsivity, in school-aged children, adolescents, and young adults with ASD. This digital smartglasses intervention can potentially be targeted at a broader array of mental health conditions that exhibit transdiagnostic attentional and social communication deficits, including schizophrenia and bipolar disorder. Further research is required to understand the clinical importance of these observed changes and to conduct longitudinal studies on this intervention with control groups and larger sample sizes.

JMIR mental health · 27 citationsread the source →

Advocacy interventions to reduce or eliminate violence and promote the physical and psychosocial well-being of women who experience intimate partner abuse.

Background: Intimate partner abuse is common worldwide, damaging the short- and long-term physical, mental, and emotional health of survivors and children. Advocacy may contribute to reducing abuse, empowering women to improve their situation by providing informal counselling and support for safety planning and increasing access to different services. Advocacy may be a stand-alone service, accepting referrals from healthcare providers, or part of a multi-component (and possibly multi-agency) intervention provided by service staff or others. Objectives: To assess the effects of advocacy interventions within or outside healthcare settings in women who have experienced intimate partner abuse. Search methods: In April 2015, we searched CENTRAL, Ovid MEDLINE, EMBASE, and 10 other databases. We also searched WHO ICTRP, mRCT, and UK Clinical Research Network (UKCRN), and examined relevant websites and reference lists with forward citation tracking of included studies. For the original review we handsearched six key journals. We also contacted first authors of eligible papers and experts in the field. Selection criteria: Randomised or quasi-randomised controlled trials comparing advocacy interventions for women with experience of intimate partner abuse versus no intervention or usual care (if advocacy was minimal and fewer than 20% of women received it). Data collection and analysis: Two review authors independently assessed risk of bias and undertook data extraction. We contacted authors for missing information needed to calculate statistics for the review and looked for adverse events. Main results: We included 13 trials involving 2141 participants aged 15 to 65 years, frequently having low socioeconomic status. The studies were quite heterogeneous in terms of methodology, study processes and design, including with regard to the duration of follow-up (postintervention to three years), although this was not associated with differences in effect. The studies also had considerable clinical heterogeneity in relation to staff delivering advocacy; setting (community, shelter, antenatal, healthcare); advocacy intensity (from 30 minutes to 80 hours); and abuse severity. Three trials evaluated advocacy within multi-component interventions. Eleven measured some form of abuse (eight scales), six assessed quality of life (three scales), and six measured depression (three scales). Countries and ethnic groups varied (one or more minority ethnic groups in the USA or UK, and local populations in Hong Kong and Peru). Setting was associated with intensity and duration of advocacy. Risk of bias was high in five studies, moderate in five, and low in three. The quality of evidence (considering multiple factors such as risk of bias, study size, missing data) was moderate to low for brief advocacy and very low for intensive advocacy. Incidence of abuse Physical abuseModerate quality pooled data from two healthcare studies (moderate risk of bias) and one community study (low risk of bias), all with 12-month follow-up data, showed no effect on physical abuse for brief (< 12 hours) advocacy interventions (standardised mean difference (SMD) 0.00, 95% confidence interval (CI) - 0.17 to 0.16; n = 558). One antenatal study (low risk of bias) showed an association between brief advocacy and reduced minor physical abuse at one year (mean difference (MD) change - 1.00, 95% CI - 1.82 to - 0.18; n = 110). An antenatal, multi-component study showed a greater likelihood of physical abuse ending (odds ratio (OR) 0.42, 95% CI 0.23 to 0.75) immediately after advocacy (number needed to treat (NNT) = 8); we cannot exclude impact from other components. Low to very low quality evidence from two intensive advocacy trials (12 hours plus duration) showed reduced severe physical abuse in women leaving a shelter at 24 months (OR 0.39, 95% CI 0.20 to 0.77; NNT = 8), but not at 12 or 36 months. Sexual abuseMeta-analysis of two studies (n = 239) showed no effect of advocacy on sexual abuse (SMD - 0.12, 95% CI - 0.37 to 0.14), agreeing with the change score (MD - 0.07, 95% CI - 0.30 to 0.16) from a third study and the OR (0.96, 95% CI 0.44 to 2.12) from a fourth antenatal, multi-component study. Emotional abuseOne study in antenatal care, rated at low risk of bias, showed reduced emotional abuse at ≤ 12-month follow-up (MD (change score) - 4.24, 95% CI - 6.42 to - 2.06; n = 110). Psychosocial health Quality of lifeMeta-analysis of two studies (high risk of bias) showed intensive advocacy slightly improved overall quality of life of women recruited from shelters (MD 0.23, 95% CI 0.00 to 0.46; n = 343) at 12-month follow-up, with greater improvement in perceived physical quality of life from a primary care study (high risk of bias; MD 4.90, 95% CI 0.98 to 8.82) immediately postintervention. Depression Meta-analysis of two studies in healthcare settings, one at high risk of bias and one at moderate risk, showed that fewer women developed depression (OR 0.31, 95% CI 0.15 to 0.65; n = 149; NNT = 4) with brief advocacy. One study at high risk of bias reported a slight reduction in depression in pregnant women immediately after the intervention (OR 0.51, 95% CI 0.20 to 1.29; n = 103; NNT = 8).There was no evidence that intensive advocacy reduced depression at ≤ 12-month follow-up (MD - 0.14, 95% CI - 0.33 to 0.05; 3 studies; n = 446) or at two years (SMD - 0.12, 95% CI - 0.36 to 0.12; 1 study; n = 265). Adverse effectsTwo women died, one who was murdered by her partner and one who committed suicide. No evidence links either death to study participation. Authors' conclusions: Results suggest some benefits from advocacy. However, most studies were underpowered. Clinical and methodological heterogeneity largely precluded pooling of trials. Therefore, there is uncertainty about the magnitude of benefit, the impact of abuse severity, and the setting. Based on the evidence reviewed, intensive advocacy may improve short-term quality of life and reduce physical abuse one to two years after the intervention for women recruited from domestic violence shelters or refuges. Brief advocacy may provide small short-term mental health benefits and reduce abuse, particularly in pregnant women and for less severe abuse.

The Cochrane database of systematic reviews · meta-analysis · 114 citationsread the source →

Diagnosing cancer in the bush: a mixed-methods study of symptom appraisal and help-seeking behaviour in people with cancer from rural Western Australia.

Background: Previous studies have focused on the treatment received by rural cancer patients and have not examined their diagnostic pathways as reasons for poorer outcomes in rural Australia. Objectives: To compare and explore symptom appraisal and help-seeking behaviour in patients with breast, lung, prostate or colorectal cancer from rural Western Australia (WA). Methods: A mixed-methods study of people recently diagnosed with breast, lung, prostate or colorectal cancer from rural WA. The time from first symptom to diagnosis (i.e. total diagnostic interval, TDI) was calculated from interviews and medical records. Results: Sixty-six participants were recruited (24 breast, 20 colorectal, 14 prostate and 8 lung cancer patients). There was a highly significant difference in time from symptom onset to seeking help between cancers (P = 0.006). Geometric mean symptom appraisal for colorectal cancer was significantly longer than that for breast and lung cancers [geometric mean differences: 2.58 (95% confidence interval, CI: 0.64-4.53), P = 0.01; 3.97 (1.63-6.30), P = 0.001, respectively]. There was a significant overall difference in arithmetic mean TDI (P = 0.046); breast cancer TDI was significantly shorter than colorectal or prostate cancer TDI [mean difference : 266.3 days (95% CI: 45.9-486.8), P = 0.019; 277.0 days, (32.1-521.9), P = 0.027, respectively]. These differences were explained by the nature and personal interpretation of symptoms, perceived as well as real problems of access to health care, optimism, stoicism, machismo, fear, embarrassment and competing demands. Conclusions: Longer symptom appraisal was observed for colorectal cancer. Participants defined core characteristics of rural Australians as optimism, stoicism and machismo. These features, as well as access to health care, contribute to later presentation of cancer.

Family practice · cohort or longitudinal · 74 citationsread the source →

Efficacy of a novel biphasic controlled-release methylphenidate formula in adults with attention-deficit/hyperactivity disorder: results of a double-blind, placebo-controlled crossover study.

Objective: To evaluate the efficacy and safety of a new biphasic multilayer-release (MLR) methylphenidate formulation in a double-blind, placebo-controlled crossover study of adults with attention-deficit/hyperactivity disorder (ADHD). Method: Adults 18 to 60 years of age with a DSM-IV diagnosis of ADHD entered a no-medication baseline week and were then randomly assigned to once-daily MLR methylphenidate or matching placebo. Patients were titrated to optimal effect over 1 to 3 weeks followed by 2 weeks of treatment on a stable dose. The same titration protocol was repeated with the alternate treatment. Clinical Global Impressions scale (CGI) and Conners' Adult ADHD Rating Scales (Self-rated, CAARS-S, and Observer-rated, CAARS-O) were collected at weekly clinic visits. The study was conducted between October 2003 and April 2004. Results: Fifty patients were randomly assigned to treatment, and 39 were analyzed in a per-protocol population (23 men, 16 women; mean age = 37.9 years). CGI-Improvement scores of subjects taking MLR methylphenidate were significantly improved compared with placebo (Global Improvement: 2.6 vs. 3.7; p = .0015). MLR methylphenidate produced improvements over placebo on the ADHD Index T scores of the CAARS-S (12.2 vs. 5.4 [change from baseline score]; p = .0083) and the CAARS-O (10.9 vs. 6.6 [change from baseline score]; p = .1404). The most frequent adverse events for MLR methylphenidate and placebo were headache (26% and 24%, respectively), anorexia (22% and 6%), insomnia (22% and 8%), nervousness (20% and 4%), and nausea (16% and 8%). There were no serious adverse events. Conclusions: Once-daily MLR methylphenidate produces significant improvements in ADHD symptoms and situational behavior in adult patients with ADHD, with a prolonged duration of effect and minimal side effects, thus having the potential to improve compliance and, therefore, treatment outcomes in routine clinical use.

The Journal of clinical psychiatry · randomised controlled trial · 37 citationsread the source →

Global patterns of mortality in international migrants: a systematic review and meta-analysis.

Background: 258 million people reside outside their country of birth; however, to date no global systematic reviews or meta-analyses of mortality data for these international migrants have been done. We aimed to review and synthesise available mortality data on international migrants. Methods: In this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Library, and Google Scholar databases for observational studies, systematic reviews, and randomised controlled trials published between Jan 1, 2001, and March 31, 2017, without language restrictions. We included studies reporting mortality outcomes for international migrants of any age residing outside their country of birth. Studies that recruited participants exclusively from intensive care or high dependency hospital units, with an existing health condition or status, or a particular health exposure were excluded. We also excluded studies limited to maternal or perinatal outcomes. We screened studies using systematic review software and extracted data from published reports. The main outcomes were all-cause and International Classification of Diseases, tenth revision (ICD-10) cause-specific standardised mortality ratios (SMRs) and absolute mortality rates. We calculated summary estimates using random-effects models. This study is registered with PROSPERO, number CRD42017073608. Findings: Of the 12 480 articles identified by our search, 96 studies were eligible for inclusion. The studies were geographically diverse and included data from all global regions and for 92 countries. 5464 mortality estimates for more than 15·2 million migrants were included, of which 5327 (97%) were from high-income countries, 115 (2%) were from middle-income countries, and 22 (<1%) were from low-income countries. Few studies included mortality estimates for refugees (110 estimates), asylum seekers (144 estimates), or labour migrants (six estimates). The summary estimate of all-cause SMR for international migrants was lower than one when compared with the general population in destination countries (0·70 [95% CI 0·65-0·76]; I2=99·8%). All-cause SMR was lower in both male migrants (0·72 [0·63-0·81]; I2=99·8%) and female migrants (0·75 [0·67-0·84]; I2=99·8%) compared with the general population. A mortality advantage was evident for refugees (SMR 0·50 [0·46-0·54]; I2=89·8%), but not for asylum seekers (1·05 [0·89-1·24]; I2=54·4%), although limited data was available on these groups. SMRs for all causes of death were lower in migrants compared with the general populations in the destination country across all 13 ICD-10 categories analysed, with the exception of infectious diseases and external causes. Heterogeneity was high across the majority of analyses. Point estimates of all-cause age-standardised mortality in migrants ranged from 420 to 874 per 100 000 population. Interpretation: Our study showed that international migrants have a mortality advantage compared with general populations, and that this advantage persisted across the majority of ICD-10 disease categories. The mortality advantage identified will be representative of international migrants in high-income countries who are studying, working, or have joined family members in these countries. However, our results might not reflect the health outcomes of more marginalised groups in low-income and middle-income countries because little data were available for these groups, highlighting an important gap in existing research. Our results present an opportunity to reframe the public discourse on international migration and health in high-income countries. Funding: Wellcome Trust, National Institute for Health Research, Medical Research Council, Alliance for Health Policy and Systems Research, Department for International Development, Fogarty International Center, Grand Challenges Canada, International Development Research Centre Canada, Inter-American Institute for Global Change Research, National Cancer Institute, National Heart, Lung and Blood Institute, National Institute of Mental Health, Swiss National Science Foundation, World Diabetes Foundation, UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, and European Society for Clinical Microbiology and Infectious Diseases (ESCMID) Study Group Research Funding for the ESCMID Study Group for Infections in Travellers and Migrants.

Lancet (London, England) · meta-analysis · 198 citationsread the source →

Circadian misalignment increases cardiovascular disease risk factors in humans.

Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. This increased risk cannot be fully explained by classic risk factors. One of the key features of shift workers is that their behavioral and environmental cycles are typically misaligned relative to their endogenous circadian system. However, there is little information on the impact of acute circadian misalignment on cardiovascular disease risk in humans. Here we show-by using two 8-d laboratory protocols-that short-term circadian misalignment (12-h inverted behavioral and environmental cycles for three days) adversely affects cardiovascular risk factors in healthy adults. Circadian misalignment increased 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 3.0 mmHg and 1.5 mmHg, respectively. These results were primarily explained by an increase in blood pressure during sleep opportunities (SBP, +5.6 mmHg; DBP, +1.9 mmHg) and, to a lesser extent, by raised blood pressure during wake periods (SBP, +1.6 mmHg; DBP, +1.4 mmHg). Circadian misalignment decreased wake cardiac vagal modulation by 8-15%, as determined by heart rate variability analysis, and decreased 24-h urinary epinephrine excretion rate by 7%, without a significant effect on 24-h urinary norepinephrine excretion rate. Circadian misalignment increased 24-h serum interleukin-6, C-reactive protein, resistin, and tumor necrosis factor-α levels by 3-29%. We demonstrate that circadian misalignment per se increases blood pressure and inflammatory markers. Our findings may help explain why shift work increases hypertension, inflammation, and cardiovascular disease risk.

Proceedings of the National Academy of Sciences of the United States of America · randomised controlled trial · 476 citationsread the source →

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.

JAMA psychiatry · randomised controlled trial · 97 citationsread the source →

Digital cognitive behavioural therapy for insomnia versus digital sleep education control in an Australian community-based sample: a randomised controlled trial.

Background: Insomnia is a prevalent condition in Australia that increases the risk of depression and anxiety symptoms. Cognitive behaviour therapy for insomnia (CBT-i) is the recommended 'first line' treatment but is accessed by a minority of people with insomnia. Aims: To improve CBT-i access in Australia, we aimed to develop and test a self-guided interactive digital CBT-i program. Methods: An online randomised controlled trial was conducted from August 2022 to August 2023 to investigate the effect of digital CBT-i, versus digital sleep education control, on symptoms of insomnia (ISI), depression (PHQ-9), anxiety (GAD-7), fatigue, sleepiness and maladaptive beliefs about sleep at 8-week follow-up. The control group accessed the intervention after the 8-week follow-up. Questionnaires were additionally administered at 16 and 24 weeks. Intent-to-treat mixed models and complete-case chi-squared analyses were used. Results: Participants included 62 adults with insomnia symptoms (age M (SD) = 52.5 (16.3), 82% female, ISI = 18.6 (2.9)). There were no between-group differences in baseline characteristics or missing 8-week data (14.5%). After adjusting for baseline scores, CBT-i was associated with lower insomnia (Diffadj (95% CI) = 7.32 (5.0-9.6), P < 0.001, d = 1.64), depression (3.36 (1.3-5.4), p = 0.002, d = 0.84), fatigue (5.2 (2.5-7.9), P < 0.001, d = 1.00) and maladaptive beliefs about sleep (11.0 (4.1-18.0), P = 0.002, d = 0.82), but not anxiety symptoms at 8 weeks (1.84 (-0.1 to 3.8), p = 0.060, d = 0.50). Compared to control, CBT-i was associated with greater rates of insomnia remission (ISI <8; 0.0%, vs 40.0%, P < 0.001) and response at 8 weeks (ISI reduction ≥6; 7.1% vs 72.0%, P < 0.001). Improvements in insomnia and depression were maintained at 24 weeks in the CBT-i group. Conclusions: This interactive digital CBT-i program resulted in large and sustained improvements in symptoms of insomnia, depression, fatigue and maladaptive beliefs about sleep in Australian adults with insomnia symptoms. Implementation programs are required to increase digital CBT-i access and uptake.

Internal medicine journal · randomised controlled trial · 7 citationsread the source →

A patient with a resistant major depression disorder treated with deep brain stimulation in the inferior thalamic peduncle.

Objective and importance: The present report explored the effect of electrical stimulation on the inferior thalamic peduncle in a patient with resistant major depression disorder (MDD). Clinical presentation: This report refers to a 49-year-old woman with a history of recurrent episodes of major depression for 20 years (12 episodes and 2 hospitalizations), fulfilling Diagnostic and Statistical Manual of Mental Disorders, 4th edition, revised, criteria for MDD; in addition, the patient met criteria for borderline personality disorder and bulimia. Her longest episode of depression with suicidal ideation began 5 years before surgery. The patient's symptom array responded poorly to different combinations of antidepressants, cognitive therapy, and electroconvulsive therapy, which induced improvement only for short periods of time. Immediately before surgery, her Global Assessment of Functioning score was 20 and her Hamilton Depression Scale score ranged from 33 to 42. The patient was proposed for surgery for MDD. Intervention: The patient had bilateral eight-contact electrodes stereotactically implanted for stimulation of areas at and around the inferior thalamic peduncle. Electrode position was corroborated by unilateral electrical stimulation searching for recruiting responses and regional direct current shifts in the electroencephalogram. Recording electrodes were replaced by tetrapolar electrodes for deep brain stimulation and connected to an internalized stimulation system for continuous bipolar stimulation at 130 Hz, 0.45 milliseconds, 2.5 V. Bimonthly follow-up included psychiatric and neuropsychological evaluations performed over the course of 24 months. After 8 months of ON stimulation, the patient entered a double-blind protocol with stimulators turned OFF. Improvement of depression measured by the Hamilton Depression Scale score was evident after initial placement of electrodes without electrical stimulation. Depression relapsed partially at the end of the first week. Electrical stimulation further improved depression, normalizing depression scores and neuropsychological performance. Patient depression scores ranked between 2 and 8 during 8 months of ON stimulation without antidepressant medication. After stimulation was turned OFF, spontaneous fluctuations in patient symptoms reflected by Hamilton Depression Scale and Global Assessment of Functioning scores were documented; these fluctuations disappeared after stimulation was turned on by Month 20. Conclusion: Complicated patients with comorbid conditions are common referrals to psychosurgery services. In this report, we present promising results of electrical stimulation of the inferior thalamic peduncle to treat recurrent unipolar depression in a patient with MDD and borderline personality disorder who responded poorly to treatment.

Neurosurgery · case report · 180 citationsread the source →

Sleep-disordered breathing, circulating exosomes, and insulin sensitivity in adipocytes.

Background: Sleep-disordered-breathing (SDB), which is characterized by chronic intermittent hypoxia (IH) and sleep fragmentation (SF), is a prevalent condition that promotes metabolic dysfunction, particularly among patients suffering from obstructive hypoventilation syndrome (OHS). Exosomes are generated ubiquitously, are readily present in the circulation, and their cargo may exert substantial functional cellular alterations in both physiological and pathological conditions. However, the effects of plasma exosomes on adipocyte metabolism in patients with OHS or in mice subjected to IH or SF mimicking SDB are unclear. Methods: Exosomes from fasting morning plasma samples from obese adults with polysomnographically-confirmed OSA before and after 3 months of adherent CPAP therapy were assayed. In addition, C57BL/6 mice were randomly assigned to (1) sleep control (SC), (2) sleep fragmentation (SF), and (3) intermittent hypoxia (HI) for 6 weeks, and plasma exosomes were isolated. Equivalent exosome amounts were added to differentiated adipocytes in culture, after which insulin sensitivity was assessed using 0 nM and 5 nM insulin-induced pAKT/AKT expression changes by western blotting. Results: When plasma exosomes were co-cultured and internalized by human naive adipocytes, significant reductions emerged in Akt phosphorylation responses to insulin when compared to exosomes obtained after 24 months of adherent CPAP treatment (n = 24; p < 0.001), while no such changes occur in untreated patients (n = 8). In addition, OHS exosomes induced significant increases in adipocyte lipolysis that were attenuated after CPAP, but did not alter pre-adipocyte differentiation. Similarly, exosomes from SF- and IH-exposed mice induced attenuated p-AKT/total AKT responses to exogenous insulin and increased glycerol content in naive murine adipocytes, without altering pre-adipocyte differentiation. Conclusions: Using in vitro adipocyte-based functional reporter assays, alterations in plasma exosomal cargo occur in SDB, and appear to contribute to adipocyte metabolic dysfunction. Further exploration of exosomal miRNA signatures in either human subjects or animal models and their putative organ and cell targets appears warranted.

International journal of obesity (2005) · randomised controlled trial · 41 citationsread the source →

WHO systematic review of prevalence of chronic pelvic pain: a neglected reproductive health morbidity.

Background: Health care planning for chronic pelvic pain (CPP), an important cause of morbidity amongst women is hampered due to lack of clear collated summaries of its basic epidemiological data. We systematically reviewed worldwide literature on the prevalence of different types of CPP to assess the geographical distribution of data, and to explore sources of variation in its estimates. Methods: We identified data available from Medline (1966 to 2004), Embase (1980 to 2004), PsycINFO (1887 to 2003), LILACS (1982 to 2004), Science Citation index, CINAHL (January 1980 to 2004) and hand searching of reference lists. Two reviewers extracted data independently, using a piloted form, on participants' characteristics, study quality and rates of CPP. We considered a study to be of high quality (valid) if had at least three of the following features: prospective design, validated measurement tool, adequate sampling method, sample size estimation and response rate >80%. We performed both univariate and multivariate meta-regression analysis to explore heterogeneity of results across studies. Results: There were 178 studies (459975 participants) in 148 articles. Of these, 106 studies were (124259 participants) on dysmenorrhoea, 54 (35973 participants) on dyspareunia and 18 (301756 participants) on noncyclical pain. There were only 19/95 (20%) less developed and 1/45 (2.2%) least developed countries with relevant data in contrast to 22/43 (51.2%) developed countries. Meta-regression analysis showed that rates of pain varied according to study quality features. There were 40 (22.5%) high quality studies with representative samples. Amongst them, the rate of dysmenorrhoea was 16.8 to 81%, that of dyspareunia was 8 to 21.8%, and that for noncyclical pain was 2.1 to 24%. Conclusion: There were few valid population based estimates of disease burden due to CPP from less developed countries. The variation in rates of CPP worldwide was due to variable study quality. Where valid data were available, a high disease burden of all types of pelvic pain was found.

BMC public health · systematic review · 346 citationsread the source →

Effect of transcutaneous auricular vagus nerve stimulation on major depressive disorder: A nonrandomized controlled pilot study.

Background: Depression presents a significant burden to both patients and society. One treatment that has emerged is vagus nerve stimulation (VNS), an FDA-approved physical treatment for depressive disorders. However, the application of this intervention has been limited by the involvement of surgery and potential side effects. The aim of this study is to explore the effectiveness of stimulating the superficial branches of the vagus nerve as a solo treatment for MDD. Methods: This is a nonrandomized, controlled study. The first cohort of patients (n=91) only received transcutaneous auricular VNS (taVNS) for 12 weeks. In the second cohort (n=69), patients first received 4 weeks of sham taVNS followed by 8 weeks of taVNS. All treatments were self-administered by the patients at home after they received training from the hospitals. The primary outcome measurement was the 24-item Hamilton Depression Rating Scale measured at weeks 0, 4, 8, and 12. Data analysis included a timelag analysis comparing (1) real and sham taVNS groups at week 4; (2) the real taVNS group at week 4 vs the sham taVNS group at week 8 (fourth week of real taVNS following 4 weeks of sham); and (3) the real taVNS group at week 8 vs the sham taVNS group at week 12 (eighth week of real taVNS following sham). Results: After four weeks of treatment, MDD patients in the taVNS group showed greater improvement than patients in the sham taVNS group as indicated by Hamilton score changes as well as response and remission rates at week four. In addition, we also found that the clinical improvements continued until week 12 during taVNS. Limitations: Patients were not randomized in this study. Conclusions: Our results suggest that taVNS is a promising, safe, and cost-effective therapeutic method for mild and moderate MDD.

Journal of affective disorders · clinical trial · 210 citationsread the source →

Severity classification on the Hamilton Depression Rating Scale.

Background: Symptom severity as a moderator of treatment response has been the subject of debate over the past 20 years. Each of the meta- and mega-analyses examining the treatment significance of depression severity used the Hamilton Depression Rating Scale (HAMD), wholly, or in part, to define severity, though the cutoff used to define severe depression varied. There is limited empirical research establishing cutoff scores for bands of severity on the HAMD. The goal of the study is to empirically establish cutoff scores on the HAMD in their allocation of patients to severity groups. Methods: Six hundred twenty-seven outpatients with current major depressive disorder were evaluated with a semi-structured diagnostic interview. Scores on the 17-item HAMD were derived from ratings according to the conversion method described by Endicott et al. (1981). The patients were also rated on the Clinical Global Index of Severity (CGI). Receiver operating curves were computed to identify the cutoff that optimally discriminated between patients with mild vs. moderate and moderate vs. severe depression. Results: HAMD scores were significantly lower in patients with mild depression than patients with moderate depression, and patients with moderate depression scored significantly lower than patients with severe depression. The cutoff score on the HAMD that maximized the sum of sensitivity and specificity was 17 for the comparison of mild vs. moderate depression and 24 for the comparison of moderate vs. severe depression. Limitations: The present study was conducted in a single outpatient practice in which the majority of patients were white, female, and had health insurance. Although the study was limited to a single site, a strength of the recruitment procedure was that the sample was not selected for participation in a treatment study, and exclusion and inclusion criteria did not reduce the representativeness of the patient groups. The analyses were based on HAMD scores extracted from ratings on the SADS. However, we used Endicott et al.'s (1981) empirically established formula for deriving a HAMD score from SADS ratings, and our results concurred with other small studies of the mean and median HAMD scores in severity groups. Conclusions: Based on this large study of psychiatric outpatients with major depressive disorder we recommend the following severity ranges for the HAMD: no depression (0-7); mild depression (8-16); moderate depression (17-23); and severe depression (≥24).

Journal of affective disorders · cohort or longitudinal · 850 citationsread the source →

Enhancing child safety and well-being through pediatric group well-child care and home visitation: The Well Baby Plus Program.

The focus of this article is on an innovative strengths-based child protection effort initiated in Beaufort, South Carolina, that involved working with local systems and structures. Specifically, the program was a school-health partnership that sought to modify services provided to low-resource families to improve child outcomes. The primary components of the prevention program were home visiting and group well visits (GWVs). This article describes the program and the effects of the combined approach on health care utilization, child health status, and parental competence for families with low socioeconomic status. A matched pairs analysis of 102 families (51 intervention and 51 comparison families) was conducted. WB+ families were significantly more likely to attend all scheduled well-child visits (65% vs. 37%) and to be fully immunized (98% vs. 82%) than matched families who received traditional pediatric care. Intervention families had significantly greater recall of anticipatory guidance on safety (65% vs. 41%) and had greater satisfaction with care. Intervention infants were also noted to be statistically less likely to be overweight at 15 months of age (8% vs. 24%). The study demonstrated benefits on child health and parenting competence among families with low socioeconomic status. Implications for practice are discussed.

Child abuse & neglect · 24 citationsread the source →

Interoceptive ability and body awareness in autism spectrum disorder.

Autism spectrum disorder (ASD) has been associated with various sensory atypicalities across multiple domains. Interoception, the ability to detect and attend to internal bodily sensations, has been found to moderate the experience of body ownership, a known difference in ASD that may affect social function. However, interoception has not been empirically examined in ASD. In the current study, 45 children (21 with ASD and 24 controls) ages 8 to 17 years completed a heartbeat perception paradigm as a measure of interoceptive ability. A subset of these children also completed the rubber hand illusion task, a multisensory paradigm probing the malleability of perceived body ownership. Although the heartbeat perception paradigm yielded comparable interoceptive awareness (IA) overall across both groups, children with ASD were superior at mentally tracking their heartbeats over longer intervals, suggesting increased sustained attention to internal cues in ASD. In addition, IA was negatively correlated with rubber hand illusion susceptibility in both groups, supporting a previously demonstrated inverse relationship between internal awareness and one's ability to incorporate external stimuli into one's perception of self. We propose a trade-off between attention to internal cues and attention to external cues, whereby attentional resources are disproportionately allocated to internal, rather than external, sensory cues in ASD.

Journal of experimental child psychology · 109 citationsread the source →

Chronic administration of caffeine, modafinil, AVL-3288 and CX516 induces time-dependent complex effects on cognition and mood in an animal model of sleep deprivation.

Objective: Caffeine and modafinil are used to reverse effects of sleep deprivation. Nicotinic alpha-7 receptor and AMPA receptor positive allosteric modulators (PAM) are also potential substances in this context. Our objective is to evaluate the effects of caffeine, modafinil, AVL-3288 (nicotinic alpha-7 PAM) and CX516 (AMPA receptor PAM) on cognition and mood in a model of sleep deprivation. Method: Modified multiple platform model is used to sleep-deprive mice for 24 days, for 8 h/day. Vehicle, Modafinil (40 mg/kg), Caffeine (5 mg/kg), CX516 (10 mg/kg), and AVL3288 (1 mg/kg) were administered intraperitoneally daily. A cognitive test battery was applied every six days for four times. The battery that included elevated plus maze, novel object recognition, and sucrose preference tests was administered on consecutive days. Results: Sleep deprivation decreased novel object recognition skill, but no significant difference was found in anxiety and depressive mood. Caffeine administration decreased anxiety-like behavior in short term, but this effect disappeared in chronic administration. Caffeine administration increased memory performance in chronic period. AVL group showed better memory performance in short term, but this effect disappeared in the rest of experiment. Although, in the modafinil group, no significant change in mood and memory was observed, anhedonia was observed in the chronic period in vehicle, caffeine and modafinil groups, but not in AVL-3288 and CX-516 groups. Conclusion: Caffeine has anxiolytic effect in acute administration. The improvement of memory in chronic period may be associated with the neuroprotective effects of caffeine. AVL-3288 had a short-term positive effect on memory, but tolerance to these effects developed over time. Furthermore, no anhedonia was observed in AVL-3288 and CX516 groups in contrast to vehicle, caffeine and modafinil groups. This indicates that AVL-3288 and CX516 may show protective effect against depression.

Pharmacology, biochemistry, and behavior · 4 citationsread the source →

How Old Is Your Brain? Slow-Wave Activity in Non-rapid-eye-movement Sleep as a Marker of Brain Rejuvenation After Long-Term Exercise in Mice.

Physical activity is beneficial for health. It has been shown to improve brain functioning and cognition, reduce severity of mood disorders, as well as facilitate healthy sleep and healthy aging. Sleep has been studied in healthy aged mice and absolute slow-wave-activity levels (SWA, electroencephalogram power between 0.75 and 4.0 Hz) in non-rapid-eye-movement sleep (NREM) were elevated, suggesting changes in brain connectivity. To investigate whether physical activity can diminish this aging-induced effect, mice of three age groups were provided with a running wheel (RW) for 1-3 months (6-months-old, n = 9; 18-months-old, n = 9; 24-months-old, n = 8) and were compared with control sedentary mice (n = 11, n = 8 and n = 9 respectively). Two weeks before the sleep-wake recordings the running wheels were removed. The electroencephalogram (EEG) and electromyogram were continuously recorded during undisturbed 24 h baseline (BL) and a sleep-deprivation was conducted during the first 6 h of the second day. Increased waking and decreased NREM sleep was found in the young RW mice, compared to young controls. These effects were not evident in the 18 and 24 months old mice. Unlike sleep architecture, we found that SWA was altered throughout the whole age spectrum. Notably, SWA was increased with aging and attenuated with exercise, exhibiting the lowest levels in the young RW mice. To utilize the cross-age revealing features of SWA, we applied machine learning techniques and found that characteristic information regarding age and exercise was enclosed in SWA. In addition, with cluster analysis, we could classify and accurately distinguish the different groups based solely on their SWA. Therefore, our study comprises a three-fold contribution: (a) effects of exercise on sleep are sustained following 2 weeks after removal of the wheel, (b) we show that EEG SWA can be used as a physiological marker of brain age in the mouse,

Frontiers in aging neuroscience · 12 citationsread the source →

Psychological impacts from COVID-19 among university students: Risk factors across seven states in the United States.

Background: University students are increasingly recognized as a vulnerable population, suffering from higher levels of anxiety, depression, substance abuse, and disordered eating compared to the general population. Therefore, when the nature of their educational experience radically changes-such as sheltering in place during the COVID-19 pandemic-the burden on the mental health of this vulnerable population is amplified. The objectives of this study are to 1) identify the array of psychological impacts COVID-19 has on students, 2) develop profiles to characterize students' anticipated levels of psychological impact during the pandemic, and 3) evaluate potential sociodemographic, lifestyle-related, and awareness of people infected with COVID-19 risk factors that could make students more likely to experience these impacts. Methods: Cross-sectional data were collected through web-based questionnaires from seven U.S. universities. Representative and convenience sampling was used to invite students to complete the questionnaires in mid-March to early-May 2020, when most coronavirus-related sheltering in place orders were in effect. We received 2,534 completed responses, of which 61% were from women, 79% from non-Hispanic Whites, and 20% from graduate students. Results: Exploratory factor analysis on close-ended responses resulted in two latent constructs, which we used to identify profiles of students with latent profile analysis, including high (45% of sample), moderate (40%), and low (14%) levels of psychological impact. Bivariate associations showed students who were women, were non-Hispanic Asian, in fair/poor health, of below-average relative family income, or who knew someone infected with COVID-19 experienced higher levels of psychological impact. Students who were non-Hispanic White, above-average social class, spent at least two hours outside, or less than eight hours on electronic screens were likely to experience lower levels of psychological impact. Multivariate modeling (mixed-effects logistic regression) showed that being a woman, having fair/poor general health status, being 18 to 24 years old, spending 8 or more hours on screens daily, and knowing someone infected predicted higher levels of psychological impact when risk factors were considered simultaneously. Conclusion: Inadequate efforts to recognize and address college students' mental health challenges, especially during a pandemic, could have long-term consequences on their health and education.

PloS one · 340 citationsread the source →

Suicidality in pediatric patients treated with antidepressant drugs.

Context: There has been concern that widely used antidepressant agents might be associated with an increased risk of suicidal ideation and behavior (suicidality) in pediatric patients. Objective: To investigate the relationship between antidepressant drugs and suicidality in pediatric patients participating in randomized, placebo-controlled trials. Data sources: Data were derived from 23 trials conducted in 9 drug company-supported programs evaluating the effectiveness of antidepressants in pediatric patients and 1 multicenter trial (the Treatment for Adolescents With Depression Study) that evaluated fluoxetine hydrochloride. Study selection: All placebo-controlled trials submitted to the Food and Drug Administration were eligible for inclusion. Evaluable data were derived from 4582 patients in 24 trials. Sixteen trials studied patients with major depressive disorder, and the remaining 8 studied obsessive-compulsive disorder (n = 4), generalized anxiety disorder (n = 2), attention-deficit/hyperactivity disorder (n = 1), and social anxiety disorder (n = 1). Only 20 trials were included in the risk ratio analysis of suicidality because 4 trials had no events in the drug or placebo groups. Data extraction: Individual patient data were available for all the trials. Data synthesis: A meta-analysis was conducted to obtain overall suicidality risk estimates for each drug individually, for selective serotonin reuptake inhibitors in depression trials as a group, and for all evaluable trials combined. There were no completed suicides in any of these trials. The multicenter trial was the only individual trial to show a statistically significant risk ratio (4.62; 95% confidence interval [CI], 1.02-20.92). The overall risk ratio for selective serotonin reuptake inhibitors in depression trials was 1.66 (95% CI, 1.02-2.68) and for all drugs across all indications was 1.95 (95% CI, 1.28-2.98). The overall risk difference for all drugs across all indications was 0.02 (95% CI, 0.01-0.03). Conclusion: Use of antidepressant drugs in pediatric patients is associated with a modestly increased risk of suicidality.

Archives of general psychiatry · meta-analysis · 596 citationsread the source →