Search the source libraries

Efficacy and safety of lisdexamfetamine for treatment of adults with moderate to severe binge-eating disorder: a randomized clinical trial.

Importance: Binge-eating disorder (BED), a public health problem associated with psychopathological symptoms and obesity and possibly with metabolic syndrome, lacks approved pharmacotherapies. Objective: To examine the efficacy and safety of lisdexamfetamine dimesylate, a dextroamphetamine prodrug, to treat moderate to severe BED. Design, setting, and participants: We performed a randomized, double-blind, parallel-group, forced dose titration, placebo-controlled clinical trial at 30 sites from May 10, 2011, through January 30, 2012. Safety and intention-to-treat analyses included 259 and 255 adults with BED, respectively. Interventions: Lisdexamfetamine dimesylate at dosages of 30, 50, or 70 mg/d or placebo were provided to study participants (1:1:1:1). Dosages were titrated across 3 weeks and maintained for 8 weeks. We followed up participants for a mean (SD) of 7 (2) days after the last dose. Main outcomes and measures: We assessed the change in binge-eating (BE) behaviors measured as days per week (baseline to week 11) with a mixed-effects model using transformed log (BE days per week) + 1. Secondary measures included BE cessation for 4 weeks. Safety assessments included treatment-emergent adverse events, vital signs, and change in weight. Results: At week 11, log-transformed BE days per week decreased with the 50-mg/d (least squares [LS] mean [SE] change, -1.49 [0.066]; P = .008) and 70-mg/d (LS mean [SE] change, -1.57 [0.067]; P < .001) treatment groups but not the 30-mg/d treatment group (LS mean [SE] change, -1.24 [0.067]; P = .88) compared with the placebo group. Nontransformed mean (SD) days per week decreased for placebo and the 30-, 50-, and 70-mg/d treatment groups by -3.3 (2.04), -3.5 (1.95), -4.1 (1.52), and -4.1 (1.57), respectively. The percentage of participants achieving 4-week BE cessation was lower with the placebo group (21.3%) compared with the 50-mg/d (42.2% [P = .01]) and 70-mg/d (50.0% [P < .001]) treatment groups. The incidence of any treatment-emergent adverse events was 58.7% for the placebo group and 84.7% for the combined treatment group. In the treatment groups, 1.5% of participants had serious treatment-emergent adverse effects. Events with a frequency of at least 5% and changes in heart rate were generally consistent with the known safety profile. The mean (SD) change in body weight was -0.1 (3.09), -3.1 (3.64), -4.9 (4.43), -4.9 (3.93), and -4.3 (4.09) kg for the placebo group, the 30-, 50-, and 70-mg/d treatment groups, and the combined treatment groups, respectively (P < .001 for each dose vs placebo group comparison in post hoc analysis). Conclusions and relevance: The 50- and 70-mg/d treatment groups demonstrated efficacy compared with the placebo group in decreased BE days, BE cessation, and global improvement. The safety profile was generally consistent with previous findings in adults with attention-deficit/hyperactivity disorder. Further investigation of lisdexamfetamine in BED is ongoing. Trial registration: clinicaltrials.gov Identifier: NCT01291173.

JAMA psychiatry · randomised controlled trial · 161 citationsread the source →

Cannabis-based medicines for chronic neuropathic pain in adults.

Background: This review is one of a series on drugs used to treat chronic neuropathic pain. Estimates of the population prevalence of chronic pain with neuropathic components range between 6% and 10%. Current pharmacological treatment options for neuropathic pain afford substantial benefit for only a few people, often with adverse effects that outweigh the benefits. There is a need to explore other treatment options, with different mechanisms of action for treatment of conditions with chronic neuropathic pain. Cannabis has been used for millennia to reduce pain. Herbal cannabis is currently strongly promoted by some patients and their advocates to treat any type of chronic pain. Objectives: To assess the efficacy, tolerability, and safety of cannabis-based medicines (herbal, plant-derived, synthetic) compared to placebo or conventional drugs for conditions with chronic neuropathic pain in adults. Search methods: In November 2017 we searched CENTRAL, MEDLINE, Embase, and two trials registries for published and ongoing trials, and examined the reference lists of reviewed articles. Selection criteria: We selected randomised, double-blind controlled trials of medical cannabis, plant-derived and synthetic cannabis-based medicines against placebo or any other active treatment of conditions with chronic neuropathic pain in adults, with a treatment duration of at least two weeks and at least 10 participants per treatment arm. Data collection and analysis: Three review authors independently extracted data of study characteristics and outcomes of efficacy, tolerability and safety, examined issues of study quality, and assessed risk of bias. We resolved discrepancies by discussion. For efficacy, we calculated the number needed to treat for an additional beneficial outcome (NNTB) for pain relief of 30% and 50% or greater, patient's global impression to be much or very much improved, dropout rates due to lack of efficacy, and the standardised mean differences for pain intensity, sleep problems, health-related quality of life (HRQoL), and psychological distress. For tolerability, we calculated number needed to treat for an additional harmful outcome (NNTH) for withdrawal due to adverse events and specific adverse events, nervous system disorders and psychiatric disorders. For safety, we calculated NNTH for serious adverse events. Meta-analysis was undertaken using a random-effects model. We assessed the quality of evidence using GRADE and created a 'Summary of findings' table. Main results: We included 16 studies with 1750 participants. The studies were 2 to 26 weeks long and compared an oromucosal spray with a plant-derived combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) (10 studies), a synthetic cannabinoid mimicking THC (nabilone) (two studies), inhaled herbal cannabis (two studies) and plant-derived THC (dronabinol) (two studies) against placebo (15 studies) and an analgesic (dihydrocodeine) (one study). We used the Cochrane 'Risk of bias' tool to assess study quality. We defined studies with zero to two unclear or high risks of bias judgements to be high-quality studies, with three to five unclear or high risks of bias to be moderate-quality studies, and with six to eight unclear or high risks of bias to be low-quality studies. Study quality was low in two studies, moderate in 12 studies and high in two studies. Nine studies were at high risk of bias for study size. We rated the quality of the evidence according to GRADE as very low to moderate. Primary outcomesCannabis-based medicines may increase the number of people achieving 50% or greater pain relief compared with placebo (21% versus 17%; risk difference (RD) 0.05 (95% confidence interval (CI) 0.00 to 0.09); NNTB 20 (95% CI 11 to 100); 1001 participants, eight studies, low-quality evidence). We rated the evidence for improvement in Patient Global Impression of Change (PGIC) with cannabis to be of very low quality (26% versus 21%;RD 0.09 (95% CI 0.01 to 0.17); NNTB 11 (95% CI 6 to 100); 1092 participants, six studies). More participants withdrew from the studies due to adverse events with cannabis-based medicines (10% of participants) than with placebo (5% of participants) (RD 0.04 (95% CI 0.02 to 0.07); NNTH 25 (95% CI 16 to 50); 1848 participants, 13 studies, moderate-quality evidence). We did not have enough evidence to determine if cannabis-based medicines increase the frequency of serious adverse events compared with placebo (RD 0.01 (95% CI -0.01 to 0.03); 1876 participants, 13 studies, low-quality evidence).Secondary outcomesCannabis-based medicines probably increase the number of people achieving pain relief of 30% or greater compared with placebo (39% versus 33%; RD 0.09 (95% CI 0.03 to 0.15); NNTB 11 (95% CI 7 to 33); 1586 participants, 10 studies, moderate quality evidence). Cannabis-based medicines may increase nervous system adverse events compared with placebo (61% versus 29%; RD 0.38 (95% CI 0.18 to 0.58); NNTH 3 (95% CI 2 to 6); 1304 participants, nine studies, low-quality evidence). Psychiatric disorders occurred in 17% of participants using cannabis-based medicines and in 5% using placebo (RD 0.10 (95% CI 0.06 to 0.15); NNTH 10 (95% CI 7 to 16); 1314 participants, nine studies, low-quality evidence).We found no information about long-term risks in the studies analysed. Subgroup analysesWe are uncertain whether herbal cannabis reduces mean pain intensity (very low-quality evidence). Herbal cannabis and placebo did not differ in tolerability (very low-quality evidence). Authors' conclusions: The potential benefits of cannabis-based medicine (herbal cannabis, plant-derived or synthetic THC, THC/CBD oromucosal spray) in chronic neuropathic pain might be outweighed by their potential harms. The quality of evidence for pain relief outcomes reflects the exclusion of participants with a history of substance abuse and other significant comorbidities from the studies, together with their small sample sizes.

The Cochrane database of systematic reviews · meta-analysis · 288 citationsread the source →

Medically unexplained symptoms, somatisation disorder and hypochondriasis: course and prognosis. A systematic review.

Objective: To study the course of medically unexplained symptoms (MUS), somatisation disorder, and hypochondriasis, and related prognostic factors. Knowledge of prognostic factors in patients presenting persistent MUS might improve our understanding of the naturalistic course and the identification of patients with a high risk of a chronic course. Methods: A comprehensive search of Medline, PsycInfo, CINAHL, and EMBASE was performed to select studies focusing on patients with MUS, somatisation disorder, and hypochondriasis, and assessing prognostic factors. Studies focusing on patients with single-symptom unexplained disorder or distinctive functional somatic syndromes were excluded. A best-evidence synthesis for the interpretation of results was used. Results: Only six studies on MUS, six studies on hypochondriasis, and one study on abridged somatisation could be included. Approximately 50% to 75% of the patients with MUS improve, whereas 10% to 30% of patients with MUS deteriorate. In patients with hypochondriasis, recovery rates vary between 30% and 50%. In studies on MUS and hypochondriasis, we found some evidence that the number of somatic symptoms at baseline influences the course of these conditions. Furthermore, the seriousness of the condition at baseline seemed to influence the prognosis. Comorbid anxiety and depression do not seem to predict the course of hypochondriasis. Conclusions: Due to the limited numbers of studies and their high heterogeneity, there is a lack of rigorous empirical evidence to identify relevant prognostic factors in patients presenting persistent MUS. However, it seems that a more serious condition at baseline is associated with a worse outcome.

Journal of psychosomatic research · systematic review · 136 citationsread the source →

Long-term clinical outcomes in survivors of severe acute respiratory syndrome and Middle East respiratory syndrome coronavirus outbreaks after hospitalisation or ICU admission: A systematic review and meta-analysis.

Objective: To determine long-term clinical outcomes in survivors of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus infections after hospitalization or intensive care unit admission. Data sources: Ovid MEDLINE, EMBASE, CINAHL Plus, and PsycINFO were searched. Study selection: Original studies reporting clinical outcomes of adult SARS and MERS survivors 3 months after admission or 2 months after discharge were included. Data extraction: Studies were graded using the Oxford Centre for Evidence-Based Medicine 2009 Level of Evidence Tool. Meta-analysis was used to derive pooled estimates for prevalence/severity of outcomes up to 6 months after hospital discharge, and beyond 6 months after discharge. Data synthesis: Of 1,169 identified studies, 28 were included in the analysis. Pooled analysis revealed that common complications up to 6 months after discharge were: impaired diffusing capacity for carbon monoxide (prevalence 27%, 95% confidence interval (CI) 15–45%); and reduced exercise capacity (mean 6-min walking distance 461 m, CI 450–473 m). The prevalences of post-traumatic stress disorder (39%, 95% CI 31–47%), depression (33%, 95% CI 20–50%) and anxiety (30%, 95% CI 10–61) beyond 6 months after discharge were considerable. Low scores on Short-Form 36 were identified beyond 6 months after discharge. Conclusion: Lung function abnormalities, psychological impairment and reduced exercise capacity were common in SARS and MERS survivors. Clinicians should anticipate and investigate similar long-term outcomes in COVID-19 survivors.

Journal of rehabilitation medicine · meta-analysis · 418 citationsread the source →

Transcutaneous electrical nerve stimulation (TENS) for fibromyalgia in adults.

Background: Fibromyalgia is characterised by persistent, widespread pain; sleep problems; and fatigue. Transcutaneous electrical nerve stimulation (TENS) is the delivery of pulsed electrical currents across the intact surface of the skin to stimulate peripheral nerves and is used extensively to manage painful conditions. TENS is inexpensive, safe, and can be self-administered. TENS reduces pain during movement in some people so it may be a useful adjunct to assist participation in exercise and activities of daily living. To date, there has been only one systematic review in 2012 which included TENS, amongst other treatments, for fibromyalgia, and the authors concluded that TENS was not effective. Objectives: To assess the analgesic efficacy and adverse events of TENS alone or added to usual care (including exercise) compared with placebo (sham) TENS; no treatment; exercise alone; or other treatment including medication, electroacupuncture, warmth therapy, or hydrotherapy for fibromyalgia in adults. Search methods: We searched the following electronic databases up to 18 January 2017: CENTRAL (CRSO); MEDLINE (Ovid); Embase (Ovid); CINAHL (EBSCO); PsycINFO (Ovid); LILACS; PEDRO; Web of Science (ISI); AMED (Ovid); and SPORTDiscus (EBSCO). We also searched three trial registries. There were no language restrictions. Selection criteria: We included randomised controlled trials (RCTs) or quasi-randomised trials of TENS treatment for pain associated with fibromyalgia in adults. We included cross-over and parallel-group trial designs. We included studies that evaluated TENS administered using non-invasive techniques at intensities that produced perceptible TENS sensations during stimulation at either the site of pain or over nerve bundles proximal (or near) to the site of pain. We included TENS administered as a sole treatment or TENS in combination with other treatments, and TENS given as a single treatment or as a course of treatments. Data collection and analysis: Two review authors independently determined study eligibility by assessing each record and reaching agreement by discussion. A third review author acted as arbiter. We did not anonymise the records of studies before assessment. Two review authors independently extracted data and assessed risk of bias of included studies before entering information into a 'Characteristics of included studies' table. Primary outcomes were participant-reported pain relief from baseline of 30% or greater or 50% or greater, and Patient Global Impression of Change (PGIC). We assessed the evidence using GRADE and added 'Summary of findings' tables. Main results: We included eight studies (seven RCTs, one quasi-RCT, 315 adults (299 women), aged 18 to 75 years): six used a parallel-group design and two used a cross-over design. Sample sizes of intervention arms were five to 43 participants. Two studies, one of which was a cross-over design, compared TENS with placebo TENS (82 participants), one study compared TENS with no treatment (43 participants), and four studies compared TENS with other treatments (medication (two studies, 74 participants), electroacupuncture (one study, 44 participants), superficial warmth (one cross-over study, 32 participants), and hydrotherapy (one study, 10 participants)). Two studies compared TENS plus exercise with exercise alone (98 participants, 49 per treatment arm). None of the studies measured participant-reported pain relief of 50% or greater or PGIC. Overall, the studies were at unclear or high risk of bias, and in particular all were at high risk of bias for sample size. Only one study (14 participants) measured the primary outcome participant-reported pain relief of 30% or greater. Thirty percent achieved 30% or greater reduction in pain with TENS and exercise compared with 13% with exercise alone. One study found 10/28 participants reported pain relief of 25% or greater with TENS compared with 10/24 participants using superficial warmth (42 °C). We judged that statistical pooling was not possible because there were insufficient data and outcomes were not homogeneous. There were no data for the primary outcomes participant-reported pain relief from baseline of 50% or greater and PGIC.There was a paucity of data for secondary outcomes. One pilot cross-over study of 43 participants found that the mean (95% confidence intervals (CI)) decrease in pain intensity on movement (100-mm visual analogue scale (VAS)) during one 30-minute treatment was 11.1 mm (95% CI 5.9 to 16.3) for TENS and 2.3 mm (95% CI 2.4 to 7.7) for placebo TENS. There were no significant differences between TENS and placebo for pain at rest. One parallel group study of 39 participants found that mean ± standard deviation (SD) pain intensity (100-mm VAS) decreased from 85 ± 20 mm at baseline to 43 ± 20 mm after one week of dual-site TENS; decreased from 85 ± 10 mm at baseline to 60 ± 10 mm after single-site TENS; and decreased from 82 ± 20 mm at baseline to 80 ± 20 mm after one week of placebo TENS. The authors of seven studies concluded that TENS relieved pain but the findings of single small studies are unlikely to be correct. One study found clinically important improvements in Fibromyalgia Impact Questionnaire (FIQ) subscales for work performance, fatigue, stiffness, anxiety, and depression for TENS with exercise compared with exercise alone. One study found no additional improvements in FIQ scores when TENS was added to the first three weeks of a 12-week supervised exercise programme. No serious adverse events were reported in any of the studies although there were reports of TENS causing minor discomfort in a total of 3 participants. The quality of evidence was very low. We downgraded the GRADE rating mostly due to a lack of data; therefore, we have little confidence in the effect estimates where available. Authors' conclusions: There was insufficient high-quality evidence to support or refute the use of TENS for fibromyalgia. We found a small number of inadequately powered studies with incomplete reporting of methodologies and treatment interventions.

The Cochrane database of systematic reviews · meta-analysis · 48 citationsread the source →

Is daytime napping an effective strategy to improve sport-related cognitive and physical performance and reduce fatigue? A systematic review and meta-analysis of randomised controlled trials.

Objective: To estimate the association between daytime napping and cognitive and physical sport performance and fatigue after normal sleep and partial sleep deprivation (less sleep duration than necessary). Design: Systematic review and meta-analysis. Data sources: The PubMed, Scopus, Web of Science, Cochrane Central, SportDiscus and PsycINFO databases. Eligibility criteria for selecting studies: Randomised controlled trials on the effect of daytime napping on sport performance and fatigue available from inception to 2 December 2022. Standardised mean differences (SMD) and their 95% compatibility intervals (CI) were estimated with the DerSimonian-Laird method through random effect models. Results: In the 22 included trials, 291 male participants (164 trained athletes and 127 physically active adults) aged between 18 and 35 years were studied. When performed after a normal night of sleep, napping from 12:30 hours to 16:50 hours (with 14:00 hours being the most frequent time) improved cognitive (SMD=0.69, 95% CI: 0.37 to 1.00; I2=71.5%) and physical performance (SMD=0.99, 95% CI: 0.67 to 1.31; I2=89.1%) and reduced the perception of fatigue (SMD=-0.76, 95% CI: -1.24 to -0.28; I2=89.5%). The positive effects of napping were also confirmed after partial sleep deprivation. Overall, the benefits were higher with a nap duration between 30 and <60 min and when the time from nap awakening to test was greater than 1 hour. Conclusions: After a night of normal sleep or partial sleep deprivation, a daytime nap between 30 and <60 min has a moderate-to-high effect on the improvement of cognitive performance and physical performance and on the reduction of perceived fatigue. Prospero registration number: CRD42020212272.

British journal of sports medicine · meta-analysis · 36 citationsread the source →

What five decades of research tells us about the effects of youth psychological therapy: A multilevel meta-analysis and implications for science and practice.

Across 5 decades, hundreds of randomized trials have tested psychological therapies for youth internalizing (anxiety, depression) and externalizing (misconduct, attention deficit and hyperactivity disorder) disorders and problems. Since the last broad-based youth meta-analysis in 1995, the number of trials has almost tripled and data-analytic methods have been refined. We applied these methods to the expanded study pool (447 studies; 30,431 youths), synthesizing 50 years of findings and identifying implications for research and practice. We assessed overall effect size (ES) and moderator effects using multilevel modeling to address ES dependency that is common, but typically not modeled, in meta-analyses. Mean posttreatment ES was 0.46; the probability that a youth in the treatment condition would fare better than a youth in the control condition was 63%. Effects varied according to multiple moderators, including the problem targeted in treatment: Mean ES at posttreatment was strongest for anxiety (0.61), weakest for depression (0.29), and nonsignificant for multiproblem treatment (0.15). ESs differed across control conditions, with "usual care" emerging as a potent comparison condition, and across informants, highlighting the need to obtain and integrate multiple perspectives on outcome. Effects of therapy type varied by informant; only youth-focused behavioral therapies (including cognitive-behavioral therapy) showed similar and robust effects across youth, parent, and teacher reports. Effects did not differ for Caucasian versus minority samples, but more diverse samples are needed. The findings underscore the benefits of psychological treatments as well as the need for improved therapies and more representative, informative, and rigorous intervention science. (PsycINFO Database Record

American Psychologist · meta-analysis · 887 citationsread the source →

Effect of intermittent versus continuous energy restriction on weight loss, maintenance and cardiometabolic risk: A randomized 1-year trial.

Background & aims: Long-term adherence to conventional weight-loss diets is limited while intermittent fasting has risen in popularity. We compared the effects of intermittent versus continuous energy restriction on weight loss, maintenance and cardiometabolic risk factors in adults with abdominal obesity and ≥1 additional component of metabolic syndrome. Methods & results: In total 112 participants (men [50%] and women [50%]) aged 21-70 years with BMI 30-45 kg/m2 (mean 35.2 [SD 3.7]) were randomized to intermittent or continuous energy restriction. A 6-month weight-loss phase including 10 visits with dieticians was followed by a 6-month maintenance phase without additional face-to-face counselling. The intermittent energy restriction group was advised to consume 400/600 kcal (female/male) on two non-consecutive days. Based on dietary records both groups reduced energy intake by ∼26-28%. Weight loss was similar among participants in the intermittent and continuous energy restriction groups (8.0 kg [SD 6.5] versus 9.0 kg [SD 7.1]; p = 0.6). There were favorable improvements in waist circumference, blood pressure, triglycerides and HDL-cholesterol with no difference between groups. Weight regain was minimal and similar between the intermittent and continuous energy restriction groups (1.1 kg [SD 3.8] versus 0.4 kg [SD 4.0]; p = 0.6). Intermittent restriction participants reported higher hunger scores than continuous restriction participants on a subjective numeric rating scale (4.7 [SD 2.2] vs 3.6 [SD 2.2]; p = 0.002). Conclusions: Both intermittent and continuous energy restriction resulted in similar weight loss, maintenance and improvements in cardiovascular risk factors after one year. However, feelings of hunger may be more pronounced during intermittent energy restriction. Trial registration: www.clinicaltrials.govNCT02480504.

Nutrition, metabolism, and cardiovascular diseases : NMCD · randomised controlled trial · 156 citationsread the source →

Transcutaneous vagus nerve stimulation boosts associative memory in older individuals.

Direct vagus nerve stimulation (dVNS) is known to improve mood, epilepsy, and memory. Memory improvements have been observed in Alzheimer's disease patients after long-term stimulation. The potential of transcutaneous vagus nerve stimulation (tVNS), a noninvasive alternative to dVNS, to alter memory performance remains unknown. We aimed to investigate the effect of a single-session tVNS on associative memory performance in healthy older individuals. To investigate this, we performed a single-blind sham-controlled randomized crossover pilot study in healthy older individuals (n = 30, 50% female). During the stimulation or sham condition, participants performed an associative face-name memory task. tVNS enhanced the number of hits of the memory task, compared with the sham condition. This effect was specific to the experimental task. Participants reported few side effects. We conclude that tVNS is a promising neuromodulatory technique to improve associative memory performance in older individuals, even after a single session. More research is necessary to investigate its underlying neural mechanisms, the impact of varying stimulation parameters, and its applicability in patients with cognitive decline.

Neurobiology of aging · randomised controlled trial · 185 citationsread the source →

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

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

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

Cost analysis of in-home telerehabilitation for post-knee arthroplasty.

Background: Rehabilitation provided through home visits is part of the continuum of care after discharge from hospital following total knee arthroplasty (TKA). As demands for rehabilitation at home are growing and becoming more difficult to meet, in-home telerehabilitation has been proposed as an alternate service delivery method. However, there is a need for robust data concerning both the effectiveness and the cost of dispensing in-home telerehabilitation. Objective: The objective of this study was to document, analyze, and compare real costs of two service delivery methods: in-home telerehabilitation and conventional home visits. Methods: The economic analysis was conducted as part of a multicenter randomized controlled trial (RCT) on telerehabilitation for TKA, and involved data from 197 patients, post-TKA. Twice a week for 8 weeks, participants received supervised physiotherapy via two delivery methods, depending on their study group allocation: in-home telerehabilitation (TELE) and home-visit rehabilitation (VISIT). Patients were recruited from eight hospitals in the province of Quebec, Canada. The TELE group intervention was delivered by videoconferencing over high-speed Internet. The VISIT group received the same intervention at home. Costs related to the delivery of the two services (TELE and VISIT) were calculated. Student's t tests were used to compare costs per treatment between the two groups. To take distance into account, the two treatment groups were compared within distance strata using two-way analyses of variance (ANOVAs). Results: The mean cost of a single session was Can $93.08 for the VISIT group (SD $35.70) and $80.99 for the TELE group (SD $26.60). When comparing both groups, real total cost analysis showed a cost differential in favor of the TELE group (TELE minus VISIT: -$263, 95% CI -$382 to -$143). However, when the patient's home was located less than 30 km round-trip from the health care center, the difference in costs between TELE and VISIT treatments was not significant (P=.25, .26, and .11 for the <10, 10-19, and 20-29 km strata, respectively). The cost of TELE treatments was lower than VISIT treatments when the distance was 30 km or more (30-49 km: $81<$103, P=.002; ≥50 km: $90<$152, P<.001). Conclusions: To our knowledge, this is the first study of the actual costs of in-home telerehabilitation covering all subcosts of telerehabilitation and distance between the health care center and the patient's home. The cost for a single session of in-home telerehabilitation compared to conventional home-visit rehabilitation was lower or about the same, depending on the distance between the patient's home and health care center. Under the controlled conditions of an RCT, a favorable cost differential was observed when the patient was more than 30 km from the provider. Stakeholders and program planners can use these data to guide decisions regarding introducing telerehabilitation as a new service in their clinic. Trial registration: International Standard Registered Clinical Study Number (ISRCTN): 66285945; http://www.isrctn.com/ISRCTN66285945 (Archived by WebCite at http://www.webcitation.org/6WlT2nuX4).

Journal of medical Internet research · randomised controlled trial · 111 citationsread the source →

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

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

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

Home dim light melatonin onsets with measures of compliance in delayed sleep phase disorder.

The dim light melatonin onset (DLMO) assists with the diagnosis and treatment of circadian rhythm sleep disorders. Home DLMOs are attractive for cost savings and convenience, but can be confounded by home lighting and sample timing errors. We developed a home saliva collection kit with objective measures of light exposure and sample timing. We report on our first test of the kit in a clinical population. Thirty-two participants with delayed sleep phase disorder (DSPD; 17 women, aged 18-52 years) participated in two back-to-back home and laboratory phase assessments. Most participants (66%) received at least one 30-s epoch of light >50 lux during the home phase assessments, but for only 1.5% of the time. Most participants (56%) collected every saliva sample within 5 min of the scheduled time. Eighty-three per cent of home DLMOs were not affected by light or sampling errors. The home DLMOs occurred, on average, 10.2 min before the laboratory DLMOs, and were correlated highly with the laboratory DLMOs (r = 0.93, P < 0.001). These results indicate that home saliva sampling with objective measures of light exposure and sample timing, can assist in identifying accurate home DLMOs.

Journal of sleep research · randomised controlled trial · 41 citationsread the source →

Family-centered advance care planning for teens with cancer.

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

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

Topiramate for the treatment of binge eating disorder associated with obesity: a placebo-controlled study.

Background: In a single-center, placebo-controlled study, topiramate reduced binge eating and weight in patients with binge eating disorder (BED) and obesity. The current investigation evaluated the safety and efficacy of topiramate in a multicenter, placebo-controlled trial. Methods: Eligible patients between 18 and 65 years with >or= 3 binge eating days/week and a body mass index (BMI) between 30 and 50 kg/m2 were randomized. Results: A total of 407 patients enrolled; 13 failed to meet inclusion criteria, resulting in 195 topiramate and 199 placebo patients. Topiramate reduced binge eating days/week (-3.5 +/- 1.9 vs. -2.5 +/- 2.1), binge episodes/week (-5.0 +/- 4.3 vs. -3.4 +/- 3.8), weight (-4.5 +/- 5.1 kg vs. .2 +/- 3.2 kg), and BMI (-1.6 +/- 1.8 kg/m2 vs. .1 +/- 1.2 kg/m2) compared with placebo (p < .001). Topiramate induced binge eating remission in 58% of patients (placebo, 29%; p < .001). Discontinuation rates were 30% in each group; adverse events (AEs) were the most common reason for topiramate discontinuation (16%; placebo, 8%). Paresthesia, upper respiratory tract infection, somnolence, and nausea were the most common AEs with topiramate. Conclusions: This multicenter study in patients with BED associated with obesity demonstrated that topiramate was well tolerated and efficacious in improving the features of BED and in reducing obesity.

Biological psychiatry · randomised controlled trial · 169 citationsread the source →

Adult romantic relationships as contexts of human development: A multimethod comparison of same-sex couples with opposite-sex dating, engaged, and married dyads.

This article presents a multimethod, multi-informant comparison of community samples of committed gay male (n=30) and lesbian (n=30) couples with both committed (n=50 young engaged and n=40 older married) and noncommitted (n=109 exclusively dating) heterosexual pairs. Specifically, in this study the quality of same- and opposite-sex relationships was examined at multiple levels of analysis via self-reports and partner reports, laboratory observations, and measures of physiological reactivity during dyadic interactions. Additionally, individuals in same-sex, engaged, and marital relationships were compared with one another on adult attachment security as assessed through the coherence of participants' narratives about their childhood experiences. Results indicated that individuals in committed same-sex relationships were generally not distinguishable from their committed heterosexual counterparts, with one exception--lesbians were especially effective at working together harmoniously in laboratory observations.

Developmental Psychology · cohort or longitudinal · 145 citationsread the source →

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

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

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

Case-mix, care pathways, and outcomes in patients with traumatic brain injury in CENTER-TBI: a European prospective, multicentre, longitudinal, cohort study.

Background: The burden of traumatic brain injury (TBI) poses a large public health and societal problem, but the characteristics of patients and their care pathways in Europe are poorly understood. We aimed to characterise patient case-mix, care pathways, and outcomes of TBI. Methods: CENTER-TBI is a Europe-based, observational cohort study, consisting of a core study and a registry. Inclusion criteria for the core study were a clinical diagnosis of TBI, presentation fewer than 24 h after injury, and an indication for CT. Patients were differentiated by care pathway and assigned to the emergency room (ER) stratum (patients who were discharged from an emergency room), admission stratum (patients who were admitted to a hospital ward), or intensive care unit (ICU) stratum (patients who were admitted to the ICU). Neuroimages and biospecimens were stored in repositories and outcome was assessed at 6 months after injury. We used the IMPACT core model for estimating the expected mortality and proportion with unfavourable Glasgow Outcome Scale Extended (GOSE) outcomes in patients with moderate or severe TBI (Glasgow Coma Scale [GCS] score ≤12). The core study was registered with ClinicalTrials.gov, number NCT02210221, and with Resource Identification Portal (RRID: SCR_015582). Findings: Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study and from 22 782 patients in the registry. In the core study, 848 (19%) patients were in the ER stratum, 1523 (34%) in the admission stratum, and 2138 (47%) in the ICU stratum. In the ICU stratum, 720 (36%) patients had mild TBI (GCS score 13-15). Compared with the core cohort, the registry had a higher proportion of patients in the ER (9839 [43%]) and admission (8571 [38%]) strata, with more than 95% of patients classified as having mild TBI. Patients in the core study were older than those in previous studies (median age 50 years [IQR 30-66], 1254 [28%] aged >65 years), 462 (11%) had serious comorbidities, 772 (18%) were taking anticoagulant or antiplatelet medication, and alcohol was contributory in 1054 (25%) TBIs. MRI and blood biomarker measurement enhanced characterisation of injury severity and type. Substantial inter-country differences existed in care pathways and practice. Incomplete recovery at 6 months (GOSE <8) was found in 207 (30%) patients in the ER stratum, 665 (53%) in the admission stratum, and 1547 (84%) in the ICU stratum. Among patients with moderate-to-severe TBI in the ICU stratum, 623 (55%) patients had unfavourable outcome at 6 months (GOSE <5), similar to the proportion predicted by the IMPACT prognostic model (observed to expected ratio 1·06 [95% CI 0·97-1·14]), but mortality was lower than expected (0·70 [0·62-0·76]). Interpretation: Patients with TBI who presented to European centres in the core study were older than were those in previous observational studies and often had comorbidities. Overall, most patients presented with mild TBI. The incomplete recovery of many patients should motivate precision medicine research and the identification of best practices to improve these outcomes. Funding: European Union 7th Framework Programme, the Hannelore Kohl Stiftung, OneMind, and Integra LifeSciences Corporation.

The Lancet. Neurology · cohort or longitudinal · 381 citationsread the source →

Pharmacotherapy for Alcohol Dependence: The 2015 Recommendations of the French Alcohol Society, Issued in Partnership with the European Federation of Addiction Societies.

Background: The latest French good practice recommendations (GPRs) for the screening, prevention, and treatment of alcohol misuse were recently published in partnership with the European Federation of Addiction Societies (EUFAS). This article aims to synthesize the GPRs focused on the pharmacotherapy of alcohol dependence. Methods: A four-member European steering committee defined the questions that were addressed to an 18-member multiprofessional working group (WG). The WG developed the GPRs based on a systematic, hierarchical, and structured literature search and submitted the document to two review processes involving 37 French members from multiple disciplines and 5 non-French EUFAS members. The final GPRs were graded A, B, or C, or expert consensus (EC) using a reference recommendation grading system. Results: The treatment of alcohol dependence consists of either alcohol detoxification or abstinence maintenance programs or drinking reduction programs. The therapeutic objective is the result of a decision made jointly by the physician and the patient. For alcohol detoxification, benzodiazepines (BZDs) are recommended in first-line (grade A). BZD dosing should be guided by regular clinical monitoring (grade B). Residential detoxification is more appropriate for patients with a history of seizures, delirium tremens, unstable psychiatric comorbidity, or another associated substance use disorder (grade B). BZDs are only justified beyond a 1-week period in the case of persistent withdrawal symptoms, withdrawal events or associated BZD dependence (grade B). BZDs should not be continued for more than 4 weeks (grade C). The dosing and duration of thiamine (vitamin B1) during detoxification should be adapted to nutritional status (EC). For relapse prevention, acamprosate and naltrexone are recommended as first-line medications (grade A). Disulfiram can be proposed as second-line option in patients with sufficient information and supervision (EC). For reducing alcohol consumption, nalmefene is indicated in first line (grade A). The second-line prescription of baclofen, up to 300 mg/day, to prevent relapse or reduce drinking should be carried out according to the "temporary recommendation for use" measure issued by the French Health Agency (EC). During pregnancy, abstinence is recommended (EC). If alcohol detoxification is conducted during pregnancy, BZD use is recommended (grade B). No medication other than those for alcohol detoxification should be initiated in pregnant or breastfeeding women (EC). In a stabilized pregnant patient taking medication to support abstinence, the continuation of the drug should be considered on a case-by-case basis, weighing the benefit/risk ratio. Only disulfiram should be always stopped, given the unknown risks of the antabuse effect on the fetus (EC). First-line treatments to help maintain abstinence or reduce drinking are off-label for people under 18 years of age and should thus be considered on a case-by-case basis after the repeated failure of psychosocial measures alone (EC). Short half-life BZDs should be preferred for the detoxification of elderly patients (grade B). The initial doses of BZDs should be reduced by 30 to 50% in elderly patients (EC). In patients with chronic alcohol-related physical disorders, abstinence is recommended (EC). Any antidepressant or anxiolytic medication should be introduced after a psychiatric reassessment after 2-4 weeks of alcohol abstinence or low-risk use (grade B). A smoking cessation program should be offered to any smokers involved in an alcohol treatment program (grade B).

CNS neuroscience & therapeutics · guideline · 72 citationsread the source →

Associations of C-reactive protein and interleukin-6 with cognitive symptoms of depression: 12-year follow-up of the Whitehall II study.

Background: A lack of longitudinal studies has made it difficult to establish the direction of associations between circulating concentrations of low-grade chronic inflammatory markers, such as C-reactive protein and interleukin-6, and cognitive symptoms of depression. The present study sought to assess whether C-reactive protein and interleukin-6 predict cognitive symptoms of depression or whether these symptoms predict inflammatory markers. Method: In a prospective occupational cohort study of British white-collar civil servants (the Whitehall II study), serum C-reactive protein, interleukin-6 and cognitive symptoms of depression were measured at baseline in 1991-1993 and at follow-up in 2002-2004, an average follow-up of 11.8 years. Symptoms of depression were measured with four items describing cognitive symptoms of depression from the General Health Questionnaire. The number of participants varied between 3339 and 3070 (mean age 50 years, 30% women) depending on the analysis. Results: Baseline C-reactive protein (beta=0.046, p=0.004) and interleukin-6 (beta=0.046, p=0.005) predicted cognitive symptoms of depression at follow-up, while baseline symptoms of depression did not predict inflammatory markers at follow-up. After full adjustment for sociodemographic, behavioural and biological risk factors, health conditions, medication use and baseline cognitive systems of depression, baseline C-reactive protein (beta=0.038, p=0.036) and interleukin-6 (beta=0.041, p=0.018) remained predictive of cognitive symptoms of depression at follow-up. Conclusions: These findings suggest that inflammation precedes depression at least with regard to the cognitive symptoms of depression.

Psychological medicine · cohort or longitudinal · 427 citationsread the source →

Beneficial effects of breast milk in the neonatal intensive care unit on the developmental outcome of extremely low birth weight infants at 18 months of age.

Objective: Beneficial effects of breast milk on cognitive skills and behavior ratings have been demonstrated previously in term and very low birth weight infants. Extremely low birth weight infants are known to be at increased risk for developmental and behavior morbidities. The benefits of breast milk that is ingested in the NICU by extremely low birth weight infants on development and behavior have not been evaluated previously. Methods: Nutrition data including enteral and parenteral feeds were collected prospectively, and follow-up assessments of 1035 extremely low birth weight infants at 18 months' corrected age were completed at 15 sites that were participants in the National Institute of Child Health and Human Development Neonatal Research Network Glutamine Trial between October 14, 1999, and June 25, 2001. Total volume of breast milk feeds (mL/kg per day) during hospitalization was calculated. Neonatal characteristics and morbidities, interim history, and neurodevelopmental and growth outcomes at 18 to 22 months' corrected age were assessed. Results: There were 775 (74.9%) infants in the breast milk and 260 (25.1%) infants in the no breast milk group. Infants in the breast milk group were similar to those in the no breast milk group in every neonatal characteristic and morbidity, including number of days of hospitalization. Mean age of first day of breast milk for the breast milk infants was 9.3 +/- 9 days. Infants in the breast milk group began to ingest non-breast milk formula later (22.8 vs 7.3 days) compared with the non-breast milk group. Age at achieving full enteral feeds was similar between the breast milk and non-breast milk groups (29.0 +/- 18 vs 27.4 +/- 15). Energy intakes of 107.5 kg/day and 105.9 kg/day during the hospitalization did not differ between the breast milk and non-breast milk groups, respectively. At discharge, 30.6% of infants in the breast milk group still were receiving breast milk. Mothers in the breast milk group were significantly more likely to be white (42% vs 27%), be married (50% vs 30%), have a college degree (22% vs 6%), and have private health insurance (34% vs 18%) compared with the no breast milk group. Mothers who were black, had a low household income (< or = dollar 20000), or had higher parity were less likely to provide breast milk feeds. The analysis of outcomes between the any human milk and no human milk groups were adjusted for maternal age, maternal education, marital status, race/ethnicity, and the other standard covariates. Children in the breast milk group were more likely to have a Bayley Mental Development Index > or = 85, higher mean Bayley Psychomotor Development Index, and higher Bayley Behavior Rating Scale percentile scores for orientation/engagement, motor regulation, and total score. There were no differences in the rates of moderate to severe cerebral palsy or blindness or hearing impairment between the 2 study groups. There were no differences in the mean weight (10.4 kg vs 10.4 kg), length (80.5 cm vs 80.5 cm), or head circumference (46.8 cm vs 46.6 cm) for the breast milk and no breast milk groups, respectively, at 18 months. Multivariate analyses, adjusting for confounders, confirmed a significant independent association of breast milk on all 4 primary outcomes: the mean Bayley (Mental Development Index, Psychomotor Development Index, Behavior Rating Scale, and incidence of rehospitalization). For every 10-mL/kg per day increase in breast milk ingestion, the Mental Development Index increased by 0.53 points, the Psychomotor Development Index increased by 0.63 points, the Behavior Rating Scale percentile score increased by 0.82 points, and the likelihood of rehospitalization decreased by 6%. In an effort to identify a threshold effect of breast milk on Bayley Mental Development Index and Psychomotor Development Index scores and Behavior Rating Scale percentile scores, the mean volume of breast milk per kilogram per day during the hospitalization was calculated, and infants in the breast milk group were divided into quintiles of breast milk ingestion adjusted for confounders. Overall, the differences across the feeding quintiles of Mental Development Index and Psychomotor Development Index were significant. There was a 14.0% difference in Behavior Rating Scale scores between the lowest and highest quintiles. For the outcomes (Mental Development Index, Psychomotor Development Index, Behavior Rating Scale, and Rehospitalization <1 year), only the values for the >80th percentile quintile of breast milk feeding were significantly different from the no breast milk values. In our adjusted regression analyses, every 10 mL/kg per day breast milk contributed 0.53 points to the Bayley Mental Development Index; therefore, the impact of breast milk ingestion during the hospitalization for infants in the highest quintile (110 mL/kg per day) on the Bayley Mental Development Index would be 10 x 0.53, or 5.3 points. Conclusions: An increase of 5 points potentially would optimize outcomes and decrease costs by decreasing the number of very low birth weight children who require special education services. The societal implications of a 5-point potential difference (one third of an SD) in IQ are substantial. The potential long-term benefit of receiving breast milk in the NICU for extremely low birth weight infants may be to optimize cognitive potential and reduce the need for early intervention and special education services.

Pediatrics · cohort or longitudinal · 344 citationsread the source →

The distribution of ''sense of coherence'' among Swedish adults: a quantitative cross-sectional population study.

Background: Antonovsky's concept of ''sense of coherence'' (SOC) has been shown to be related to health. The aim of this study was to describe the distribution of SOC scores and their components in an adult Swedish population aged 20-80 years. Methods: A random sample of 910 individuals from Jönköping, Sweden, aged 20, 30, 40, 50, 60, 70 and 80 years, of which 589 agreed to participate in an oral health examination. The participants answered Antonovsky's 13-item version of ''the life orientation questionnaire scale''. The response to the items and the distribution of the three components of comprehensibility, manageability and meaningfulness were analyzed for different age groups and genders using mean values and standard deviations, Student's t-test and ANOVA. Results: A total of 526 individuals, 263 men and 263 women, answered all 13 questions and constituted the final material for the study (response rate 89%). The individual SOC score increased with age. The 20 year olds had a statistically significantly lower SOC score compared with the other age groups and 55% of them had a low SOC (< or = 66 points) compared with 17% of the 80 year olds. Men in the 60 and 70 year age groups had a statistically significantly higher SOC score compared with women of the same age. Conclusions: The individual distribution of SOC varied with age and gender. Twenty year olds had a significantly lower SOC score compared with elderly age groups. Elderly men had a statistically significantly higher SOC score compared with women of the same age.

Scandinavian journal of public health · cohort or longitudinal · 60 citationsread the source →

Behavioral genetic analyses of prosocial behavior in adolescents.

Prosocial behavior is an important aspect of normal social and psychological development. Adult and child twin studies typically estimate the heritability of prosocial behavior to be between 30 and 50%, although relatively little is known about genetic and environmental influences upon prosocial behavior in adolescence. We therefore examined reports of prosocial behavior in a large longitudinal family study of 1160 adolescent twin pairs (aged between 13 and 19 years). Prosocial behavior was assessed at two time points by self-report and at the second time point by additional parent-ratings using the Strengths and Difficulties Questionnaire (SDQ; Goodman, 1997). Adolescent females were reported to be significantly more prosocial than males (p < .001). Univariate analyses primarily showed moderate heritability and large nonshared environmental influences. There was a moderate genetic correlation between self- and parent-reported prosocial behaviour, suggesting that both types of rater were tapping into genetically overlapping constructs. Longitudinal analyses revealed that continuity was largely explained by genes. Unique environmental influences were predominantly time-specific and were the major source of individual differences.

Developmental science · cohort or longitudinal · 35 citationsread the source →

Does cognitive-behavioural therapy influence the long-term outcome of generalized anxiety disorder? An 8–14 year follow-up of two clinical trials

BACKGROUND: Generalized anxiety disorder is a common condition of excessive worry and tension which tends to run a chronic course associated with significant psychiatric and medical problems. Cognitive behaviour therapy (CBT) has been shown to be of clinical value in about 50% of cases with treatment gains maintained over follow-up periods ranging from 6 to 12 months. The potential value of CBT over the longer term has not been subject to rigorous investigation. METHOD: Results are reported of 8-14 year follow-up of two randomized controlled trials of cognitive-behaviour therapy for generalized anxiety disorder employing structured interview with an assessor blind to initial treatment condition. Comparison groups included medication and placebo in one study based in primary care, and analytical psychotherapy in the other based in secondary care. Follow-up samples (30% and 55% of trial entrants) were broadly representative of the original cohorts. RESULTS: Overall, 50% of participants were markedly improved of whom 30-40% were recovered (i.e. free of symptoms). Outcome was significantly worse for the study based in secondary care in which the clinical presentation of participants was more complex and severe. For a minority (30-40%), mainly from the secondary care study, outcome was poor. Treatment with CBT was associated with significantly lower overall severity of symptomatology and less interim treatment, in comparison with non-CBT conditions, but there was no evidence that CBT influenced diagnostic status, probability of recovery or patient perceptions of overall improvement. CONCLUSIONS: Both CBT and the complexity and severity of presenting problems appear to influence the long-term outcome of GAD.

Psychological Medicine · randomised controlled trial · 93 citationsread the source →

The visual scoring of sleep and arousal in infants and children.

Age is probably the single most crucial factor determining how humans sleep. Age and level of vigilance significantly influence the electroencephalogram (EEG) and the polysomnogram (PSG). The Pediatric Task Force provide an evidence-based review of the age-related development of the polysomnographic features of sleep in neonates, infants, and children, assessing the reliability and validity of these features, and assessing alternative methods of measurement. We used this annotated supporting text to develop rules for scoring sleep and arousals in infants and children. A pediatric EEG or PSG can only be determined to be normal by assessing whether the EEG patterns are appropriate for maturational age. Sleep in infants at term can be scored as NREM and REM sleep because all the polysomnographic and EEG features of REM sleep are present and quiet sleep, if not NREM sleep, is at least "not REM sleep." The dominant posterior rhythm (DPR) of relaxed wakefulness increases in frequency with age: (1) 3.5-4.5 Hz in 75% of normal infants by 3-4 months post-term; (2) 5-6 Hz in most infants 5-6 months post-term; 3) 6 Hz in 70% of normal children by 2 months of age; and 3) 8 Hz (range 7.5-9.5 Hz) in 82% of normal children age 3 years, 9 Hz in 65% of 9-year-olds, and 10 Hz in 65% of 15-year-old controls. Sleep spindles in children occur independently at two different frequencies and two different scalp locations: 11.0-12.75 Hz over the frontal and 13.0-14.75 Hz over the centroparietal electrodes; these findings are most prominent in children younger than 13 years. Centroparietal spikes are often maximal over the vertex (Cz), less often maximal over the left central (C3) or right central (C4) EEG derivation. About 50% of sleep spindles within a particular infant's PSG are asynchronous before 6 months of age, 30% at 1 year. Based on this, we recommend that: (1) sleep spindles be scored as a polysomnographic signature of NREM stage 2 sleep (N2) at whatever age they are first seen in a PSG, typically present by 2 to 3 months post-term; (2) identify and score sleep spindles from the frontal and centroparietal EEG derivations, especially in infants and children younger than 13 years. NREM sleep in an infant or child can be scored if the dominant posterior rhythm occupies <50% of a 30-second epoch, and one or more of the following EEG patterns appear: (1) a diffuse lower voltage mixed frequency activity; (2) hypnagogic hypersynchrony; (3) rhythmic anterior theta of drowsiness; (4) diffuse high voltage occipital delta slowing; (5) runs or bursts of diffuse, frontal, frontocentral, or occipital maximal rhythmic 3-5 Hz slowing; (6) vertex sharp waves; and/or (7) post-arousal hypersynchrony. K complexes first appear 5 months post-term and are usually present by 6 months post-term, whereas clearly recognizable vertex sharp waves are most often seen 16 months post-term. Vertex sharp waves are best seen over the central (Cz, C3, C4) and K complexes over the frontal (Fz, F3, F4) electrodes. Slow wave activity (SWA) of slow wave sleep (SWS) is first seen as early as 2 to 3 months post-term and is usually present 4 to 4.5 months post-term. SWA of SWS in an infant or child often has a peak-to-peak amplitude of 100 to 400 microV. Based on consensus voting we recommended scoring N1, N2, and N3 corresponding to NREM 1, 2, and SWS whenever it was recognizable in an infant's PSG, usually by 4 to 4.5 months post-term (as early as 2-3 months post-term). Epochs of NREM sleep which contain no sleep spindles, K complexes, or SWA would be scored as N1; those which contain either K complexes or sleep spindles and <20% SWS as N2, and those in which >20% of the 30-second epoch contain 0.5 to 2 Hz >75 microV (usually 100-400 microV) activity as N3. The DPR should be scored in the EEG channel that is best observed, (typically occipital), but DPR reactive to eye opening can be seen in central electrodes. Because sleep spindles occur independently over the frontal and central regions in children, they should be scored whether they occur in the frontal or central regions. Because sleep spindles are asynchronous before age 2 years, simultaneous recording of left and right frontal and central activity may be warranted in children 1-2 years of age. Simultaneous recording of left, right, and midline central electrodes may be appropriate because of the asynchronous nature of sleep spindles before age 2 years, but reliability testing is needed. Evidence has shown that the PSG cannot reliably be used to identify neurological deficits or to predict behavior or outcome in infants because of significant diversity of results, even in normal infants. Normal sleep EEG patterns and architecture are present in the first year of life, even in infants with severe neurological compromise. Increasing evidence suggests that sleep and its disorders play critical roles in the development of healthy children and healthy adults thereafter. Reliability studies comparing head-to-head different scoring criteria, recording techniques, and derivations are needed so that future scoring recommendations can be based on evidence rather than consensus opinion. We need research comparing clinical outcomes with PSG measures to better inform clinicians and families exactly what meaning a PSG has in evaluating a child's suspected sleep disorder.

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · review · 206 citationsread the source →

Psychotherapy of obsessive-compulsive disorder and spectrum: established facts and advances, 1995-2005.

Dropout rates and refractory cases persist, for reasons that remain unexplained. There are few predictor variables and few innovative approaches to deal with them. New treatment approaches must be developed to improve treatment response even for the responders. Studies show that symptoms are reduced minimally (30% 50%). No new ways of dealing with treatment-refractory cases have been developed. Studies now include more co-morbid cases, however, and their inclusion may account for some of the lack of progress in improvement rates. It needs to be seen whether patients who have one or more comorbid conditions do as well as patients who do not have comorbidity and whether the number or type of comorbid disorders accounts for treatment response. Perhaps better results would be seen with pure OCD cases. Certainly results now are more generalizable to clinical practice. Now it is important to look for alternative treatment approaches and to apply cognitive therapy to more specific problems. Cognitive therapy seems to be helpful with the disorders of the obsessive-compulsive spectrum. The attrition rate is lower when cognitive therapy is used in the treatment of hypochondriasis, and cognitive therapy also is helpful in reducing OVI , which is more severe in body dysmorphic disorder and hypochondriasis. The role of cognitive therapy in OVI needs further exploration.

The Psychiatric clinics of North America · review · 15 citationsread the source →

Gender differences in hypothalamic-pituitary-adrenal (HPA) axis reactivity.

The present study was designed to determine whether there are gender differences in hormonal response patterns to HPA axis activation. To this end, two methods of activating the HPA axis were employed: a standardized psychological stress test and a pharmacological challenge. Healthy subjects (mean age 23.4 years, SD 7.0 years) completed a naloxone challenge and/or the modified Trier Social Stress Test (TSST). For the naloxone challenge, two baseline blood samples were obtained. Placebo was then administered (0 min), followed by increasing doses of intravenous naloxone (50, 100, 200 and 400 microg/kg) at 30-min intervals. Post-placebo blood samples were collected at 15-min intervals for 180 min. The TSST consisted of 5 min of public speaking followed by 5 min of mental arithmetic exercises. Three baseline and five post-TSST blood samples were drawn. Eighty subjects (53 male, 27 female) underwent the TSST. Following the psychological stressor, adrenocorticotropin (ACTH) and cortisol responses were significantly greater in male subjects compared to female subjects (z=-2.34, p=0.019 and z=-2.12, p=0.034, respectively). Seventy-two subjects (52 male, 20 female) underwent HPA axis activation induced by naloxone. In contrast to the TSST, cortisol responses to the naloxone challenge were significantly greater in female subjects compared to male subjects (z=4.11, p<0.001). Forty-one subjects (25 male, 16 female) completed both the TSST and naloxone challenge. In this subset, ACTH and cortisol responses to the TSST did not differ significantly by gender, although the effect size was moderate to large. Adrenocorticotropin and cortisol responses to the naloxone challenge were significantly greater in female subjects compared to male subjects (z=2.29, p=0.022 and z=4.34, p<0.001, respectively). In summary, male subjects had greater HPA axis responses to a psychological stressor than female subjects, and females had greater hormonal reactivity than males to pharmacological stimulation with naloxone. Such differences are of interest as potential contributors to gender differences in health risks.

Psychoneuroendocrinology · cohort or longitudinal · 200 citationsread the source →

Euthanasia and Assisted Suicide of Patients With Psychiatric Disorders in the Netherlands 2011 to 2014.

Importance: Euthanasia or assisted suicide (EAS) of psychiatric patients is increasing in some jurisdictions such as Belgium and the Netherlands. However, little is known about the practice, and it remains controversial. Objectives: To describe the characteristics of patients receiving EAS for psychiatric conditions and how the practice is regulated in the Netherlands. Design, setting, and participants: This investigation reviewed psychiatric EAS case summaries made available online by the Dutch regional euthanasia review committees as of June 1, 2015. Two senior psychiatrists used directed content analysis to review and code the reports. In total, 66 cases from 2011 to 2014 were reviewed. Main outcomes and measures: Clinical and social characteristics of patients, physician review process of the patients' requests, and the euthanasia review committees' assessments of the physicians' actions. Results: Of the 66 cases reviewed, 70% (n = 46) were women. In total, 32% (n = 21) were 70 years or older, 44% (n = 29) were 50 to 70 years old, and 24% (n = 16) were 30 to 50 years old. Most had chronic, severe conditions, with histories of attempted suicides and psychiatric hospitalizations. Most had personality disorders and were described as socially isolated or lonely. Depressive disorders were the primary psychiatric issue in 55% (n = 36) of cases. Other conditions represented were psychotic, posttraumatic stress or anxiety, somatoform, neurocognitive, and eating disorders, as well as prolonged grief and autism. Comorbidities with functional impairments were common. Forty-one percent (n = 27) of physicians performing EAS were psychiatrists. Twenty-seven percent (n = 18) of patients received the procedure from physicians new to them, 14 of whom were physicians from the End-of-Life Clinic, a mobile euthanasia clinic. Consultation with other physicians was extensive, but 11% (n = 7) of cases had no independent psychiatric input, and 24% (n = 16) of cases involved disagreement among consultants. The euthanasia review committees found that one case failed to meet legal due care criteria. Conclusions and relevance: Persons receiving EAS for psychiatric disorders in the Netherlands are mostly women and of diverse ages, with complex and chronic psychiatric, medical, and psychosocial histories. The granting of their EAS requests appears to involve considerable physician judgment, usually involving multiple physicians who do not always agree (sometimes without independent psychiatric input), but the euthanasia review committees generally defer to the judgments of the physicians performing the EAS.

JAMA psychiatry · 129 citationsread the source →

"I would never want to have a mental health diagnosis on my record": A survey of female physicians on mental health diagnosis, treatment, and reporting.

Introduction: Physicians have high rates of suicide and depression. Most state medical boards require disclosure of mental health problems on physician licensing applications, which has been theorized to increase stigma about mental health and prevent help-seeking among physicians. Methods: We surveyed a convenience sample of female physician-parents on a closed Facebook group. The anonymous 24-question survey asked about mental health history and treatment, perceptions of stigma, opinions about state licensing questions on mental health, and personal experiences with reporting. Results: 2106 women responded, representing all 50 states and the District of Columbia. Most respondents were aged 30-59. Almost 50% of women believed that they had met the criteria for mental illness but had not sought treatment. Key reasons for avoiding care included a belief they could manage independently, limited time, fear of reporting to a medical licensing board, and the belief that diagnosis was embarrassing or shameful. Only 6% of physicians with formal diagnosis or treatment of mental illness had disclosed to their state. Conclusions: Women physicians report substantial and persistent fear regarding stigma which inhibits both treatment and disclosure. Licensing questions, particularly those asking about a diagnosis or treatment rather than functional impairment may contribute to treatment reluctance.

General hospital psychiatry · 114 citationsread the source →

Pharmacokinetics of once-daily darunavir-ritonavir and atazanavir-ritonavir over 72 hours following drug cessation.

The object of this study was to investigate the pharmacokinetics of darunavir-ritonavir and atazanavir-ritonavir once-daily dosing over 72 h (h) following drug intake cessation. Volunteers received darunavir-ritonavir at 800 and 100 mg, respectively, once daily for 10 days, followed by a 7-day washout period, and atazanavir-ritonavir at 300 and 100 mg, respectively, once daily for 10 days. Full pharmacokinetic profiles were assessed for each phase for the 72 h following day 10. Pharmacokinetic parameters were determined over 24 h and to the last measurable concentration by noncompartmental methods. Seventeen subjects completed the study. The geometric mean (GM) terminal elimination half-life to 72 h of darunavir was 6.48 h, which was lower than the 0- to 24-h half-life (10.70 h). The terminal elimination half-life of atazanavir was 6.74 h, which was lower than the 0- to 24-h half-life (13.72 h). All subjects but one had darunavir concentrations higher than the target of 550 ng/ml for protease-resistant HIV isolates (equivalent to 10 times the protein-binding-corrected 50% inhibitory concentration [IC(50)] for wild-type virus) at 24 h postdose, and 14 out of 17 had concentrations higher than the target at 30 h postdose (GM of 1,088 and 851 ng/ml). All subjects had atazanavir concentrations above the suggested minimum effective concentration of 150 ng/ml (equivalent to 10 times the protein-binding-corrected IC(50) for wild-type virus) at 24 and 30 h postdose (GM of 693 and 392 ng/ml). Two of 17 and 5 of 17 subjects were above target at 48 h postdose while on darunavir-ritonavir and atazanavir-ritonavir. Ritonavir half-life to 72 h was 6.84 h with darunavir and 6.07 with atazanavir. This study investigated the pharmacokinetic forgiveness of two boosted protease inhibitors. Although the rates of decline of darunavir and atazanavir slightly increased as ritonavir concentrations declined, most individuals had concentrations 6 h after the end of the ideal dosing interval of 24 h which were above the cutoff used to define therapeutic concentrations.

Antimicrobial agents and chemotherapy · clinical trial · 31 citationsread the source →

A randomized trial of interpersonal psychotherapy, problem solving therapy, and supportive therapy for major depressive disorder in women with breast cancer.

Purpose: Breast cancer (BC) is a risk factor for major depressive disorder (MDD), yet little research has tested the efficacy of different psychotherapies for depressed women with BC. This study, the largest to date, compared outcomes of three evidence-based, 12-week therapies in treating major depressive disorder among women with breast cancer. Methods: This randomized trial compared interpersonal psychotherapy (IPT), problem solving therapy (PST), and brief supportive psychotherapy (BSP). Conducted at the outpatient clinic of the New York State Psychiatric Institute/Columbia University, the trial offered bilingual treatment by treatment-specific psychotherapists supervised by treatment experts. The primary outcome was change in the Hamilton Depression Rating Scale (HAM-D) at 12 weeks. Secondary outcomes included other validated patient-reported outcomes for depression and quality of life. Results: Of 179 women with breast cancer screening positive for depression at the Columbia Cancer Center, 134 eligible patients signed informed treatment consent. Half of patients were Hispanic and economically disadvantaged. Most women had stage I (35.2%) or II (36.9%) BC; 9% had stage IV. The three brief psychotherapies showed similar improvements on the HAM-D, with large pre-post effect sizes (d ~ 1.0); a priori defined response rates were 35% for IPT, 50% for PST and 31% for BSP, and remission rates 25%, 30% and 27%, respectively. The three treatments also showed similar improvements in the Quality of Life Enjoyment and Satisfaction Questionnaire. Dropout was high, ranging from 37 to 52% across treatments. Predictors of dropout included having < 16 years of education and annual family income < $20,000. Conclusions: Among patients who completed treatment, all three psychotherapies were associated with similar, meaningful improvements in depression. Physical distance between the oncology and psychiatric treatment sites might have contributed to high dropout. This study suggests various psychotherapy approaches may benefit patients with breast cancer and major depression.

Breast cancer research and treatment · randomised controlled trial · 28 citationsread the source →

The Economic Impact of Smoking and of Reducing Smoking Prevalence: Review of Evidence.

Background: Tobacco smoking is the cause of many preventable diseases and premature deaths in the UK and around the world. It poses enormous health- and non-health-related costs to the affected individuals, employers, and the society at large. The World Health Organization (WHO) estimates that, globally, smoking causes over US$500 billion in economic damage each year. Objectives: This paper examines global and UK evidence on the economic impact of smoking prevalence and evaluates the effectiveness and cost effectiveness of smoking cessation measures. Study selection: SEARCH METHODS We used two major health care/economic research databases, namely PubMed and the National Institute for Health Research (NIHR) database that contains the British National Health Service (NHS) Economic Evaluation Database; Cochrane Library of systematic reviews in health care and health policy; and other health-care-related bibliographic sources. We also performed hand searching of relevant articles, health reports, and white papers issued by government bodies, international health organizations, and health intervention campaign agencies. SELECTION CRITERIA The paper includes cost-effectiveness studies from medical journals, health reports, and white papers published between 1992 and July 2014, but included only eight relevant studies before 1992. Most of the papers reviewed reported outcomes on smoking prevalence, as well as the direct and indirect costs of smoking and the costs and benefits of smoking cessation interventions. We excluded papers that merely described the effectiveness of an intervention without including economic or cost considerations. We also excluded papers that combine smoking cessation with the reduction in the risk of other diseases. DATA COLLECTION AND ANALYSIS The included studies were assessed against criteria indicated in the Cochrane Reviewers Handbook version 5.0.0. OUTCOMES ASSESSED IN THE REVIEWPrimary outcomes of the selected studies are smoking prevalence, direct and indirect costs of smoking, and the costs and benefits of smoking cessation interventions (eg, "cost per quitter", "cost per life year saved", "cost per quality-adjusted life year gained," "present value" or "net benefits" from smoking cessation, and "cost savings" from personal health care expenditure). Main results: The main findings of this study are as follows: The costs of smoking can be classified into direct, indirect, and intangible costs. About 15% of the aggregate health care expenditure in high-income countries can be attributed to smoking. In the US, the proportion of health care expenditure attributable to smoking ranges between 6% and 18% across different states. In the UK, the direct costs of smoking to the NHS have been estimated at between £2.7 billion and £5.2 billion, which is equivalent to around 5% of the total NHS budget each year. The economic burden of smoking estimated in terms of GDP reveals that smoking accounts for approximately 0.7% of China's GDP and approximately 1% of US GDP. As part of the indirect (non-health-related) costs of smoking, the total productivity losses caused by smoking each year in the US have been estimated at US$151 billion. The costs of smoking notwithstanding, it produces some potential economic benefits. The economic activities generated from the production and consumption of tobacco provides economic stimulus. It also produces huge tax revenues for most governments, especially in high-income countries, as well as employment in the tobacco industry. Income from the tobacco industry accounts for up to 7.4% of centrally collected government revenue in China. Smoking also yields cost savings in pension payments from the premature death of smokers. Smoking cessation measures could range from pharmacological treatment interventions to policy-based measures, community-based interventions, telecoms, media, and technology (TMT)-based interventions, school-based interventions, and workplace interventions. The cost per life year saved from the use of pharmacological treatment interventions ranged between US$128 and US$1,450 and up to US$4,400 per quality-adjusted life years (QALYs) saved. The use of pharmacotherapies such as varenicline, NRT, and Bupropion, when combined with GP counseling or other behavioral treatment interventions (such as proactive telephone counseling and Web-based delivery), is both clinically effective and cost effective to primary health care providers. Price-based policy measures such as increase in tobacco taxes are unarguably the most effective means of reducing the consumption of tobacco. A 10% tax-induced cigarette price increase anywhere in the world reduces smoking prevalence by between 4% and 8%. Net public benefits from tobacco tax, however, remain positive only when tax rates are between 42.9% and 91.1%. The cost effectiveness ratio of implementing non-price-based smoking cessation legislations (such as smoking restrictions in work places, public places, bans on tobacco advertisement, and raising the legal age of smokers) range from US$2 to US$112 per life year gained (LYG) while reducing smoking prevalence by up to 30%-82% in the long term (over a 50-year period).Smoking cessation classes are known to be most effective among community-based measures, as they could lead to a quit rate of up to 35%, but they usually incur higher costs than other measures such as self-help quit-smoking kits. On average, community pharmacist-based smoking cessation programs yield cost savings to the health system of between US$500 and US$614 per LYG.Advertising media, telecommunications, and other technology-based interventions (such as TV, radio, print, telephone, the Internet, PC, and other electronic media) usually have positive synergistic effects in reducing smoking prevalence especially when combined to deliver smoking cessation messages and counseling support. However, the outcomes on the cost effectiveness of TMT-based measures have been inconsistent, and this made it difficult to attribute results to specific media. The differences in reported cost effectiveness may be partly attributed to varying methodological approaches including varying parametric inputs, differences in national contexts, differences in advertising campaigns tested on different media, and disparate levels of resourcing between campaigns. Due to its universal reach and low implementation costs, online campaign appears to be substantially more cost effective than other media, though it may not be as effective in reducing smoking prevalence. School-based smoking prevalence programs tend to reduce short-term smoking prevalence by between 30% and 70%. Total intervention costs could range from US$16,400 to US$580,000 depending on the scale and scope of intervention. The cost effectiveness of school-based programs show that one could expect a saving of approximately between US$2,000 and US$20,000 per QALY saved due to averted smoking after 2-4 years of follow-up. Workplace-based interventions could represent a sound economic investment to both employers and the society at large, achieving a benefit-cost ratio of up to 8.75 and generating 12-month employer cost savings of between $150 and $540 per nonsmoking employee. Implementing smoke-free workplaces would also produce myriads of new quitters and reduce the amount of cigarette consumption, leading to cost savings in direct medical costs to primary health care providers. Workplace interventions are, however, likely to yield far greater economic benefits over the long term, as reduced prevalence will lead to a healthier and more productive workforce. Conclusions: We conclude that the direct costs and externalities to society of smoking far outweigh any benefits that might be accruable at least when considered from the perspective of socially desirable outcomes (ie, in terms of a healthy population and a productive workforce). There are enormous differences in the application and economic measurement of smoking cessation measures across various types of interventions, methodologies, countries, economic settings, and health care systems, and these may have affected the comparability of the results of the studies reviewed. However, on the balance of probabilities, most of the cessation measures reviewed have not only proved effective but also cost effective in delivering the much desired cost savings and net gains to individuals and primary health care providers.

Tobacco use insights · review · 189 citationsread the source →

Effects of a popular exercise and weight loss program on weight loss, body composition, energy expenditure and health in obese women.

Objective: To determine the safety and efficacy of altering the ratio of carbohydrate and protein in low-energy diets in conjunction with a popular exercise program in obese women. Design: Matched, prospective clinical intervention study to assess efficacy of varying ratios of carbohydrate and protein intake in conjunction with a regular exercise program. Participants: One-hundred sixty one sedentary, obese, pre-menopausal women (38.5 ± 8.5 yrs, 164.2 ± 6.7 cm, 94.2 ± 18.8 kg, 34.9 ± 6.4 kg.m⁻², 43.8 ± 4.2%) participated in this study. Participants were weight stable and not participating in additional weight loss programs. Methods: Participants were assigned to either a no exercise + no diet control (CON), a no diet + exercise group (ND), or one of four diet + exercise groups (presented as kcals; % carbohydrate: protein: fat): 1) a high energy, high carbohydrate, low protein diet (HED) [2,600; 55:15:30%], 2) a very low carbohydrate, high protein diet (VLCHP) [1,200 kcals; 63:7:30%], 3) a low carbohydrate, moderate protein diet (LCMP) [1,200 kcals; 50:20:30%] and 4) a high carbohydrate, low protein diet (HCLP) [1,200 kcals; 55:15:30%]. Participants in exercise groups (all but CON) performed a pneumatic resistance-based, circuit training program under supervision three times per week. Measurements: Anthropometric, body composition, resting energy expenditure (REE), fasting blood samples and muscular fitness assessments were examined at baseline and weeks 2, 10 and 14. Results: All groups except CON experienced significant reductions (P < 0.05 - 0.001) in waist circumference over 14 weeks. VLCHP, LCHP and LPHC participants experienced similar but significant (P < 0.05 - 0.001) reductions in body mass when compared to other groups. Delta responses indicated that fat loss after 14 weeks was significantly greatest in VLCHP (95% CI: -5.2, -3.2 kg), LCMP (-4.0, -1.9 kg) and HCLP (-3.8, -2.1 kg) when compared to other groups. Subsequent reductions in % body fat were significantly greater in VLCHP, LCMP and HCLP participants. Initial dieting decreased (P < 0.05) relative REE similarly in all groups. All exercise groups significantly (P < 0.05) improved in muscular fitness, but these improvements were not different among groups. Favorable but non-significant mean changes occurred in lipid panels, glucose and HOMA-IR. Leptin levels decreased (P < 0.05) in all groups, except for CON, after two weeks of dieting and remained lower throughout the 14 week program. Exercise participation resulted in significant improvements in quality of life and body image. Conclusion: Exercise alone (ND) appears to have minimal impact on measured outcomes with positive outcomes apparent when exercise is combined with a hypoenergetic diet. Greater improvements in waist circumference and body composition occurred when carbohydrate is replaced in the diet with protein. Weight loss in all diet groups (VLCHP, LCMP and HCLP) was primarily fat and stimulated improvements in markers of cardiovascular disease risk, body composition, energy expenditure and psychosocial parameters.

Nutrition & metabolism · 58 citationsread the source →

Clinical correlates of vitamin D deficiency in established psychosis.

Background: Suboptimal vitamin D levels have been identified in populations with psychotic disorders. We sought to explore the relationship between vitamin D deficiency, clinical characteristics and cardiovascular disease risk factors among people with established psychosis. Methods: Vitamin D levels were measured in 324 community dwelling individuals in England with established psychotic disorders, along with measures of mental health, cardiovascular risk and lifestyle choices. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D (25-OHD) levels below 10 ng/ml (equivalent to <25 nmol/L) and "sufficient" Vitamin D as above 30 ng/ml (>50 nmol/L). Results: The mean 25-OHD serum level was 12.4 (SD 7.3) ng/ml, (range 4.0-51.7 ng/ml). Forty nine percent (n = 158) were vitamin D deficient, with only 14 % (n = 45) meeting criteria for sufficiency. Accounting for age, gender, ethnicity and season of sampling, serum 25-OHD levels were negatively correlated with waist circumference (r = -0.220, p < 0.002), triglycerides (r = -0.160, p = 0.024), total cholesterol (r = -0.144, p = 0.043), fasting glucose (r = -0.191, p = 0.007), HbA1c (r = -0.183, p = 0.01), and serum CRP levels (r = -0.211, p = 0.003) and were linked to the presence of metabolic syndrome. Conclusions: This is the largest cross sectional study of serum 25-OHD levels in community dwelling individuals with established psychosis, indicating a high level of vitamin D deficiency. Lower vitamin D levels are associated with increased cardiovascular disease risk factors and in particular metabolic syndrome. Further research is needed to define appropriate protocols for vitamin D testing and supplementation in practice to see if this can improve cardiovascular disease risk. Trial registration: ISRCTN number is ISRCTN58667926 Date of registration: 23/04/2010.

BMC psychiatry · 39 citationsread the source →

Men living through multiple miscarriages: protocol for a qualitative exploration of experiences and support requirements.

Introduction: Up to 1 in 4 pregnancies and 1 in 20 subsequent pregnancies end in miscarriage. Despite such prevalence the psychosocial effects are often unrecognised and unsupported. In the absence of any biomedical sequelae among men such marginalisation may be intensified. Men living through multiple miscarriages may also find any grief or anxiety intensified by loss of hope for future parenthood, but robust qualitative studies of these experiences are limited. We aim to rectify the deficiency. Methods and analysis: Our qualitative study will adopt the sounds of silence framework designed by Serrant-Green to hear the voices of populations possibly marginalised. We will listen and learn from 30 to 50 men with a history of two or more miscarriages. The research participants will be recruited from a recurrent miscarriage clinic at a large tertiary hospital in England, and from advertisements to be disseminated by the project sponsor and miscarriage charities. Individual telephone interviews supported by a semistructured discussion guide will be audio-recorded, transcribed and anonymised. The transcriptions and any field notes will be interpreted by the framework method of Ritchie and Lewis embedded within the sounds of silence framework. Tentative findings will be presented to research participants in face-to-face focus group discussion, to enable member synthesis to enhance authenticity. The focus group discussion will be audio-recorded, transcribed, anonymised and similarly interpreted to contribute to our final synthesis. Ethics and dissemination: The protocol of this project received a favourable opinion from the West Midlands South Birmingham Research Ethics Committee (16/WM/0423). Results will be submitted for publication in peer-reviewed journals and at conferences, and disseminated via newsletters and social media of our clinical collaborators and miscarriage charities. Outputs are anticipated to inform future policy and practice in the management of multiple miscarriages. Trial registration number: ISRCTN 21828561.

BMJ open · 2 citationsread the source →

Premenstrual Dysphoric Disorder Symptoms Following Ovarian Suppression: Triggered by Change in Ovarian Steroid Levels But Not Continuous Stable Levels.

Objective: Premenstrual dysphoric disorder (PMDD) symptoms are eliminated by ovarian suppression and stimulated by administration of ovarian steroids, yet they appear with ovarian steroid levels indistinguishable from those in women without PMDD. Thus, symptoms could be precipitated either by an acute change in ovarian steroid levels or by stable levels above a critical threshold playing a permissive role in expression of an underlying infradian affective "pacemaker." The authors attempted to determine which condition triggers PMDD symptoms. Method: The study included 22 women with PMDD, ages 30 to 50 years. Twelve women who experienced symptom remission after 2-3 months of GnRH agonist-induced ovarian suppression (leuprolide) then received 1 month of single-blind (participant only) placebo and then 3 months of continuous combined estradiol/progesterone. Primary outcome measures were the Rating for Premenstrual Tension observer and self-ratings completed every 2 weeks during clinic visits. Multivariate repeated-measure ANOVA for mixed models was employed. Results: Both self- and observer-rated scores on the Rating for Premenstrual Tension were significantly increased (more symptomatic) during the first month of combined estradiol/progesterone compared with the last month of leuprolide alone, the placebo month, and the second and third months of estradiol/progesterone. There were no significant differences in symptom severity between the last month of leuprolide alone, placebo month, or second and third months of estradiol/progesterone. Finally, the Rating for Premenstrual Tension scores in the second and third estradiol/progesterone months did not significantly differ. Conclusions: The findings demonstrate that the change in estradiol/progesterone levels from low to high, and not the steady-state level, was associated with onset of PMDD symptoms. Therapeutic efforts to modulate the change in steroid levels proximate to ovulation merit further study.

The American journal of psychiatry · 141 citationsread the source →

Asperger syndrome in males over two decades: Quality of life in relation to diagnostic stability and psychiatric comorbidity.

This study examined objective quality of life (work, academic success, living situation, relationships, support system) and subjective quality of life (Sense of Coherence and Short-Form Health Survey-36) in an adult sample of males ( n = 50, mean age: 30 years) with Asperger syndrome diagnosed in childhood and followed prospectively over two decades. The association between long-term diagnostic stability of an autism spectrum disorder and/or comorbid psychiatric disorders with quality of life was also examined. The results showed great variability as regards quality of life. The subsample that no longer fulfilled an autism spectrum disorder had full-time jobs or studies (10/11), independent living (100%), and reported having two or more friends (100%). In the stable autism spectrum disorder group, 41% had full-time job or studies, 51% lived independently, and 33% reported two or more friends, and a significant minority had specialized employments, lived with support from the government, or had no friends. Academic success was positively correlated with IQ. A majority of the total group scored average Sense of Coherence scores, and the mean for Short-Form Health Survey-36 was above average regarding psychical health and below average regarding mental health. Stability of autism spectrum disorder diagnosis was associated with objective but not subjective quality of life, while psychiatric comorbidity was associated with subjective but not objective quality of life.

Autism : the international journal of research and practice · 41 citationsread the source →

The Prevalence and Burden of Non-AIDS Comorbidities Among Women Living With or at Risk for Human Immunodeficiency Virus Infection in the United States.

Background: The prevalence and burden of age-related non-AIDS comorbidities (NACMs) are poorly characterized among women living with HIV (WLWH). Methods: Virologically suppressed WLWH and HIV-seronegative participants followed in the Women's Interagency HIV Study (WIHS) through at least 2009 (when >80% of WLWH used antiretroviral therapy) were included, with outcomes measured through 31 March 2018. Covariates, NACM number, and prevalence were summarized at most recent WIHS visit. We used linear regression models to determine NACM burden by HIV serostatus and age. Results: Among 3232 women (2309 WLWH, 923 HIV-seronegative) with median observation of 15.3 years, median age and body mass index (BMI) were 50 years and 30 kg/m2, respectively; 65% were black; 70% ever used cigarettes. WLWH had a higher mean NACM number than HIV-seronegative women (3.6 vs 3.0, P < .0001) and higher prevalence of psychiatric illness, dyslipidemia, non-AIDS cancer, kidney, liver, and bone disease (all P < .01). Prevalent hypertension, diabetes, and cardiovascular and lung disease did not differ by HIV serostatus. Estimated NACM burden was higher among WLWH versus HIV-seronegative women in those aged 40-49 (P < .0001) and ≥60 years (P = .0009) (HIV × age interaction, P = .0978). In adjusted analyses, NACM burden was associated with HIV, age, race, income, BMI, alcohol abstinence, cigarette, and crack/cocaine use; in WLWH, additional HIV-specific indices were not associated, aside from recent abacavir use. Conclusions: Overall, NACM burden was high in the cohort, but higher in WLWH and in certain age groups. Non-HIV traditional risk factors were significantly associated with NACM burden in WLWH and should be prioritized in clinical guidelines for screening and intervention to mitigate comorbidity burden in this high-risk population.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 58 citationsread the source →

Transcutaneous Spinal Cord Stimulation Induces Temporary Attenuation of Spasticity in Individuals with Spinal Cord Injury.

Epidural spinal cord stimulation (SCS) is currently regarded as a breakthrough procedure for enabling movement after spinal cord injury (SCI), yet one of its original applications was for spinal spasticity. An emergent method that activates similar target neural structures non-invasively is transcutaneous SCS. Its clinical value for spasticity control would depend on inducing carry-over effects, because the surface-electrode-based approach cannot be applied chronically. We evaluated single-session effects of transcutaneous lumbar SCS in 12 individuals with SCI by a test-battery approach, before, immediately after and 2 h after intervention. Stimulation was applied for 30 min at 50 Hz with an intensity sub-threshold for eliciting reflexes in lower extremity muscles. The tests included evaluations of stretch-induced spasticity (Modified Ashworth Scale [MAS] sum score, pendulum test, electromyography-based evaluation of tonic stretch reflexes), clonus, cutaneous-input-evoked spasms, and the timed 10 m walk test. Across participants, the MAS sum score, clonus, and spasms were significantly reduced immediately after SCS, and all spasticity measures were improved 2 h post-intervention, with large effect sizes and including clinically meaningful improvements. The effect on walking speed varied across individuals. We further conducted a single-case multi-session study over 6 weeks to explore the applicability of transcutaneous SCS as a home-based therapy. Self-application of the intervention was successful; weekly evaluations suggested progressively improving therapeutic effects during the active period and carry-over effects for 7 days. Our results suggest that transcutaneous SCS can be a viable non-pharmacological option for managing spasticity, likely working through enhancing pre- and post-synaptic spinal inhibitory mechanisms, and may additionally serve to identify responders to treatments with epidural SCS.

Journal of neurotrauma · 120 citationsread the source →

Randomized, Controlled Trial of an Advance Care Planning Video Decision Support Tool for Patients With Advanced Heart Failure.

Background: Conversations about goals of care and cardiopulmonary resuscitation (CPR)/intubation for patients with advanced heart failure can be difficult. This study examined the impact of a video decision support tool and patient checklist on advance care planning for patients with heart failure. Methods: This was a multisite, randomized, controlled trial of a video-assisted intervention and advance care planning checklist versus a verbal description in 246 patients ≥64 years of age with heart failure and an estimated likelihood of death of >50% within 2 years. Intervention participants received a verbal description for goals of care (life-prolonging care, limited care, and comfort care) and CPR/intubation plus a 6-minute video depicting the 3 levels of care, CPR/intubation, and an advance care planning checklist. Control subjects received only the verbal description. The primary analysis compared the proportion of patients preferring comfort care between study arms immediately after the intervention. Secondary outcomes were CPR/intubation preferences and knowledge (6-item test; range, 0-6) after intervention. Results: In the intervention group, 27 (22%) chose life-prolonging care, 31 (25%) chose limited care, 63 (51%) selected comfort care, and 2 (2%) were uncertain. In the control group, 50 (41%) chose life-prolonging care, 27 (22%) selected limited care, 37 (30%) chose comfort care, and 8 (7%) were uncertain (P<0.001). Intervention participants (compared with control subjects) were more likely to forgo CPR (68% versus 35%; P<0.001) and intubation (77% versus 48%; P<0.001) and had higher mean knowledge scores (4.1 versus 3.0; P<0.001). Conclusions: Patients with heart failure who viewed a video were more informed, more likely to select a focus on comfort, and less likely to desire CPR/intubation compared with patients receiving verbal information only. Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01589120.

Circulation · randomised controlled trial · 88 citationsread the source →

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

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

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

A systematic review and meta-analysis of correlates of prolonged grief disorder in adults exposed to violent loss.

Background: Violent loss (i.e. loss through homicide, suicide, or accident) is associated with high levels of prolonged grief disorder (PGD). Objective: The current meta-analysis aims at identifying correlates of PGD in adults exposed to violent loss. Method: We conducted a systematic literature search in PsycINFO, PsycARTICLES, PubMed, Web of Science, and Scopus. We used the Pearson correlation coefficient r as an effect size measure and a random effects model was applied to calculate effect sizes. Results: Thirty-seven eligible studies published between 2003 and 2017 (N = 5911) revealed 29 potential correlates. Most studies used a cross-sectional design. Analyses revealed large significant effect sizes for comorbid psychopathology (r = .50-.59), suicidality (r = .41, 95% confidence interval [CI] [.30; .52]), and rumination (r = .42, 95% CI [.31; .52]), while medium effect sizes were found for exposure to traumatic events and factors concerning the relationship to the deceased. Small effect sizes emerged for sociodemographic characteristics, multiple loss, physical symptoms, and religious beliefs. Ten variables did not show a significant association with PGD. Heterogeneity and a small number of studies assessing certain correlates were observed. Conclusions: The associations with psychological disorders may indicate shared mechanisms of psychopathology. Moreover, we recommend that clinicians carefully assess suicidal ideation among individuals with PGD who have been exposed to violent loss. Further research is warranted using longitudinal study designs with large sample sizes to understand the relevance of these factors for the development of PGD.

European journal of psychotraumatology · review · 84 citationsread the source →

Pharmacotherapies for sleep disturbances in dementia.

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

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

Prevalence of psychological morbidities among general population, healthcare workers and COVID-19 patients amidst the COVID-19 pandemic: A systematic review and meta-analysis.

This review was done to synthesize the existing evidence on the prevalence of various psychological morbidities among general public, healthcare workers and COVID-19 patients amidst this pandemic situation. Systematic searches were conducted in various databases and search engines such as Medline, Chinese national knowledge infrastructure, Cochrane library, ScienceDirect, and Google Scholar from inception until 22 April 2020. Newcastle Ottawa scale was used to assess the quality of included studies. We carried out a meta-analysis with random-effects model and reported pooled prevalence with 95% confidence intervals (CIs).A total of 50 studies were included in the review. Only seven studies (14%) had low risk of bias. Pooled prevalence rate of psychological morbidities includes poor sleep quality (40%), stress (34%), psychological distress (34%), insomnia (30%), post-traumatic stress symptoms (27%), anxiety (26%), depression (26%). Pooled prevalence rate of psychological morbidities with respect to impact of event due to COVID-19 pandemic was 44% (95%CI-42% to 47%). The burden of these psychological morbidities was highest among the COVID-19 patients followed by healthcare workers and general population.

Psychiatry research · meta-analysis · 355 citationsread the source →

Effect of psychological therapy on disease activity, psychological comorbidity, and quality of life in inflammatory bowel disease: a systematic review and meta-analysis.

Background: Inflammatory bowel disease is associated with psychological comorbidity and impaired quality of life. Psychological comorbidity could affect the natural history of inflammatory bowel disease. Psychological therapies might therefore have beneficial effects on disease activity, mood, and quality of life in patients with inflammatory bowel disease. We did a systematic review and meta-analysis examining these issues. Methods: In this systematic review and meta-analysis, we searched MEDLINE, Embase, Embase Classic, PsychINFO, and the Cochrane Central Register of Controlled Trials for articles published between 1947 and Sept 22, 2016. Randomised controlled trials (RCTs) recruiting patients with inflammatory bowel disease aged at least 16 years that compared psychological therapy with a control intervention or usual treatment were eligible. We pooled dichotomous data to obtain relative risks of induction of remission in active disease or prevention of relapse of quiescent disease, with 95% CIs. We pooled continuous data to estimate standardised mean differences in disease activity indices, anxiety, depression, perceived stress, and quality-of-life scores in patients dichotomised into those with clinically active or quiescent disease, with 95% CIs. We extracted data from published reports and contacted the original investigators of studies for which the required data were not available. We pooled all data using a random-effects model. Findings: The search identified 1824 studies, with 14 RCTs of 1196 patients eligible for inclusion. The relative risk of relapse of quiescent inflammatory bowel disease with psychological therapy versus control was 0·98 (95% CI 0·77-1·24; p=0·87; I2=50%; six trials; 518 patients). We observed a significant difference in depression scores (standardised mean difference -0·17 [-0·33 to -0·01]; p=0·04; I2=0%; seven trials; 605 patients) and quality of life (0·30 [0·07-0·52]; p=0·01; I2=42%; nine trials; 578 patients) with psychological therapy versus control at the end of therapy for patients with quiescent disease. However, these beneficial effects were lost at final point of follow-up (depression scores -0·11 [-0·27 to 0·05], p=0·17, I2=0%, eight trials, 593 patients; quality of life 0·15 [-0·05 to 0·34], p=0·14, I2=22%, ten trials, 577 patients). When we assessed the effect of individual physiological therapies on quality of life, only cognitive behavioural therapy had any significant beneficial effect (0·37 [0·02-0·72]). We noted no effect on disease activity indices or other psychological wellbeing scores when compared with control in patients with quiescent disease. Dichotomous data for induction of remission and continuous data for change in clinical disease activity indices, depression, anxiety, and perceived stress scores were only reported in one RCT of patients with active disease. Quality of life was assessed in two RCTs of patients with active disease, but was not significantly different between intervention and control groups (0·27 [-0·05 to 0·59]). Interpretation: Psychological therapies, and cognitive behavioural therapy in particular, might have small short-term beneficial effects on depression scores and quality of life in patients with inflammatory bowel disease. Further RCTs of these interventions in patients with coexistent psychological distress are required. Funding: None.

The lancet. Gastroenterology & hepatology · meta-analysis · 163 citationsread the source →

Effective behaviour change techniques for physical activity and healthy eating in overweight and obese adults; systematic review and meta-regression analyses.

Purpose: This systematic review aims to explain the heterogeneity in results of interventions to promote physical activity and healthy eating for overweight and obese adults, by exploring the differential effects of behaviour change techniques (BCTs) and other intervention characteristics. Methods: The inclusion criteria specified RCTs with ≥ 12 weeks' duration, from January 2007 to October 2014, for adults (mean age ≥ 40 years, mean BMI ≥ 30). Primary outcomes were measures of healthy diet or physical activity. Two reviewers rated study quality, coded the BCTs, and collected outcome results at short (≤6 months) and long term (≥12 months). Meta-analyses and meta-regressions were used to estimate effect sizes (ES), heterogeneity indices (I2) and regression coefficients. Results: We included 48 studies containing a total of 82 outcome reports. The 32 long term reports had an overall ES = 0.24 with 95% confidence interval (CI): 0.15 to 0.33 and I2 = 59.4%. The 50 short term reports had an ES = 0.37 with 95% CI: 0.26 to 0.48, and I2 = 71.3%. The number of BCTs unique to the intervention group, and the BCTs goal setting and self-monitoring of behaviour predicted the effect at short and long term. The total number of BCTs in both intervention arms and using the BCTs goal setting of outcome, feedback on outcome of behaviour, implementing graded tasks, and adding objects to the environment, e.g. using a step counter, significantly predicted the effect at long term. Setting a goal for change; and the presence of reporting bias independently explained 58.8% of inter-study variation at short term. Autonomy supportive and person-centred methods as in Motivational Interviewing, the BCTs goal setting of behaviour, and receiving feedback on the outcome of behaviour, explained all of the between study variations in effects at long term. Conclusion: There are similarities, but also differences in effective BCTs promoting change in healthy eating and physical activity and BCTs supporting maintenance of change. The results support the use of goal setting and self-monitoring of behaviour when counselling overweight and obese adults. Several other BCTs as well as the use of a person-centred and autonomy supportive counselling approach seem important in order to maintain behaviour over time. Trial registration: PROSPERO CRD42015020624.

The international journal of behavioral nutrition and physical activity · meta-analysis · 494 citationsread the source →

Skin-to-skin care for procedural pain in neonates.

Background: Skin-to-skin care (SSC), often referred to as 'kangaroo care' (KC) due to its similarity with marsupial behaviour of ventral maternal-infant contact, is one non-pharmacological intervention for pain control in infants. Objectives: The primary objectives were to determine the effect of SSC alone on pain from medical or nursing procedures in neonates compared to no intervention, sucrose or other analgesics, or additions to simple SSC such as rocking; and to determine the effects of the amount of SSC (duration in minutes), method of administration (e.g. who provided the SSC) of SSC in reducing pain from medical or nursing procedures in neonatesThe secondary objectives were to determine the safety of SSC care for relieving procedural pain in infants; and to compare the SSC effect in different postmenstrual age subgroups of infants. Search methods: For this update, we used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 1); MEDLINE via PubMed (1966 to 25 February 2016); Embase (1980 to 25 February 2016); and CINAHL (1982 to 25 February 2016). We also searched clinical trials' databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials. Selection criteria: Studies with randomisation or quasi-randomisation, double- or single-blinded, involving term infants (≥ 37 completed weeks' postmenstrual age (PMA) to a maximum of 44 weeks' PMA and preterm infants (< 37 completed weeks PMA) receiving SSC for painful procedures conducted by healthcare professionals. Data collection and analysis: The main outcome measures were physiological or behavioural pain indicators and composite pain scores. A mean difference (MD) with 95% confidence interval (CI) using a fixed-effect model was reported for continuous outcome measures. We included variations on type of tissue-damaging procedure, provider of care, and duration of SSC. Main results: Twenty-five studies (n = 2001 infants) were included. Nineteen studies (n = 1065) used heel lance as the painful procedure, one study combined venepuncture and heel stick (n = 50), three used intramuscular injection (n = 776), one used 'vaccination' (n = 60), and one used tape removal (n = 50). The studies were generally strong and had low or uncertain risk of bias. Blinding of the intervention was not possible, making them subject to high risk, depending on the method of scoring outcomes. Seventeen studies (n = 810) compared SSC to a no-treatment control. Although 15 studies measured heart rate during painful procedures, data from only five studies (n = 161) could be combined for a mean difference (MD) of -10.78 beats per minute (95% CI -13.63 to -7.93) favouring SSC. Meta-analysis of four studies (n = 120) showed no difference in heart rate following the painful procedure (MD 0.08, 95% CI -4.39 to 4.55). Two studies (n = 38) reported heart rate variability with no significant differences. Two studies (n = 101) in a meta-analysis on oxygen saturation at 30 and 60 seconds following the painful procedure did not show a difference. Duration of crying meta-analysis was performed on four studies (n = 133): two (n = 33) investigated response to heel lance (MD = -34.16, 95% CI -42.86 to -25.45), and two (n = 100) following IM injection (MD = -8.83, 95% CI -14.63 to -3.02), favouring SSC. Five studies, one consisting of two substudies (n = 267), used the Premature Infant Pain Profile (PIPP) as a primary outcome, which favoured SCC at 30 seconds (MD -3.21, 95% CI -3.94 to -2.47), at 60 seconds (3 studies; n = 156) (MD -1.64, 95% CI -2.86 to -0.43), and at 90 seconds (n = 156) (MD -1.28, 95% CI -2.53 to -0.04); but at 120 seconds there was no difference (n = 156) (MD 0.07, 95% CI -1.11 to 1.25). No studies on return of heart rate to baseline level, cortisol levels, and facial actions could be combined for meta-analysis findings. Eight studies compared SSC to another intervention with or without a no-treatment control. Two cross-over studies (n = 80) compared mother versus other provider (father, another female) on PIPP scores at 30, 60, 90, and 120 seconds with no significant difference. When SSC was compared to other interventions, there were not enough similar studies to pool results in an analysis. One study compared SSC (n = 640) with and without dextrose and found that the combination was most effective and that SSC alone was more effective than dextrose alone. Similarly, in another study SSC was more effective than oral glucose for heart rate (n = 95). SSC either in combination with breastfeeding or alone was favoured over a no-treatment control, but not different to breastfeeding. One study compared SSC alone and in combination with both sucrose and breastfeeding on heart rate (HR), NIPS scores, and crying time (n = 127). The combinations were more effective than SSC alone for NIPS and crying. Expressed breast milk was compared to SSC in one study (n = 50) and found both equally effective on PIPP scores. There were not enough participants with similar outcomes and painful procedures to compare age groups or duration of SSC. No adverse events were reported in any of the studies. Authors' conclusions: SSC appears to be effective as measured by composite pain indicators with both physiological and behavioural indicators and, independently, using heart rate and crying time; and safe for a single painful procedure. Purely behavioural indicators tended to favour SSC but with facial actions there is greater possibility of observers not being blinded. Physiological indicators were mixed although the common measure of heart rate favoured SSC. Two studies compared mother-providers to others, with non-significant results. There was more heterogeneity in the studies with behavioural or composite outcomes. There is a need for replication studies that use similar, clearly defined outcomes. Studies examining optimal duration of SSC, gestational age groups, repeated use, and long-term effects of SSC are needed. Of interest would be to study synergistic effects of SSC with other interventions.

The Cochrane database of systematic reviews · meta-analysis · 158 citationsread the source →

Cognitive behavioral therapy for insomnia in patients with mental disorders and comorbid insomnia: A systematic review and meta-analysis.

Almost 70% of patients with mental disorders report sleep difficulties and 30% fulfill the criteria for insomnia disorder. Cognitive behavioral therapy for insomnia (CBT-I) is the first-line treatment for insomnia according to current treatment guidelines. Despite this circumstance, insomnia is frequently treated only pharmacologically especially in patients with mental disorders. The aim of the present meta-analysis was to quantify the effects of CBT-I in patients with mental disorders and comorbid insomnia on two outcome parameters: the severity of insomnia and mental health. The databases PubMed, CINHAL (Ebsco) und PsycINFO (Ovid) were searched for randomized controlled trials on adult patients with comorbid insomnia and any mental disorder comparing CBT-I to placebo, waitlist or treatment as usual using self-rating questionnaires as outcomes for either insomnia or mental health or both. The search resulted in 1994 records after duplicate removal of which 22 fulfilled the inclusion criteria and were included for the meta-analysis. The comorbidities were depression (eight studies, 491 patients), post-traumatic stress disorder (PTSD, four studies, 216 patients), alcohol dependency (three studies, 79 patients), bipolar disorder (one study, 58 patients), psychosis (one study, 50 patients) and mixed comorbidities within one study (five studies, 189 patients). The effect sizes for the reduction of insomnia severity post treatment were 0.5 (confidence interval, CI, 0.3-0.8) for patients with depression, 1.5 (CI 1.0-1.9) for patients with PTSD, 1.4 (CI 0.9-1.9) for patients with alcohol dependency, 1.2 (CI 0.8-1.7) for patients with psychosis/bipolar disorder, and 0.8 (CI 0.1-1.6) for patients with mixed comorbidities. Effect sizes for the reduction of insomnia severity were moderate to large at follow-up. Regarding the effects on comorbid symptom severity, effect sizes directly after treatment were 0.5 (CI 0.1-0.8) for depression, 1.3 (CI 0.6-1.9) for PTSD, 0.9 (CI 0.3-1.4) for alcohol dependency in only one study, 0.3 (CI -0.1 - 0.7, insignificant) for psychosis/bipolar, and 0.8 (CI 0.1-1.5) for mixed comorbidities. There were no significant effects on comorbid symptoms at follow-up. Together, these significant, stable medium to large effects indicate that CBT-I is an effective treatment for patients with insomnia and a comorbid mental disorder, especially depression, PTSD and alcohol dependency. CBT-I is also an effective add-on treatment with the aim of improving mental health in patients with depression, PTSD, and symptom severity in outpatients with mixed diagnoses. Thus, in patients with mental disorders and comorbid insomnia, given the many side effects of medication, CBT-I should be considered as a first-line treatment.

Sleep medicine reviews · meta-analysis · 263 citationsread the source →

Relaxin for the treatment of patients with acute heart failure (Pre-RELAX-AHF): a multicentre, randomised, placebo-controlled, parallel-group, dose-finding phase IIb study.

Background: Most patients admitted for acute heart failure have normal or increase blood pressure. Relaxin is a natural human peptide that affects multiple vascular control pathways, suggesting potential mechanisms of benefit for such patients. We assessed the dose response of relaxin's effect on symptom relief, other clinical outcomes, and safety. Methods: In a placebo-controlled, parallel-group, dose-ranging study, 234 patients with acute heart failure, dyspnoea, congestion on chest radiograph, and increased brain natriuretic peptide (BNP) or N-terminal prohormone of BNP, mild-to-moderate renal insufficiency, and systolic blood pressure greater than 125 mm Hg were recruited from 54 sites in eight countries and enrolled within 16 h of presentation. Patients were randomly assigned, in a double-blind manner via a telephone-based interactive voice response system, to standard care plus 48-h intravenous infusion of placebo (n=62) or relaxin 10 microg/kg (n=40), 30 microg/kg (n=43), 100 microg/kg (n=39), or 250 microg/kg (n=50) per day. Several clinical endpoints were explored to assess whether intravenous relaxin should be pursued in larger studies of acute heart failure, to identify an optimum dose, and to help to assess endpoint selection and power calculations. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT00520806. Findings: In the modified intention-to-treat population, 61 patients were assessed in the placebo group, 40 in the relaxin 10 microg/kg per day group, 42 in the relaxin 30 microg/kg per day group, 37 in the relaxin 100 microg/kg per day group, and 49 in the relaxin 250 microg/kg per day group. Dyspnoea improved with relaxin 30 microg/kg compared with placebo, as assessed by Likert scale (17 of 42 patients [40%] moderately or markedly improved at 6 h, 12 h, and 24 h vs 14 of 61 [23%]; p=0.044) and visual analogue scale through day 14 (8214 mm x h [SD 8712] vs 4622 mm x h [9003]; p=0.053). Length of stay was 10.2 days (SD 6.1) for relaxin-treated patients versus 12.0 days (7.3) for those given placebo, and days alive out of hospital were 47.9 (10.1) versus 44.2 (14.2). Cardiovascular death or readmission due to heart or renal failure at day 60 was reduced with relaxin (2.6% [95% CI 0.4-16.8] vs 17.2% [9.6-29.6]; p=0.053). The number of serious adverse events was similar between groups. Interpretation: When given to patients with acute heart failure and normal-to-increased blood pressure, relaxin was associated with favourable relief of dyspnoea and other clinical outcomes, with acceptable safety.

Lancet (London, England) · randomised controlled trial · 314 citationsread the source →

Melatonin agonist tasimelteon (VEC-162) for transient insomnia after sleep-time shift: two randomised controlled multicentre trials.

Background: Circadian rhythm sleep disorders are common causes of insomnia for millions of individuals. We did a phase II study to establish efficacy and physiological mechanism, and a phase III study to confirm efficacy of the melatonin agonist tasimelteon (VEC-162) for treatment of transient insomnia associated with shifted sleep and wake time. Methods: We undertook phase II and phase III randomised, double-blind, placebo-controlled, parallel-group studies. In a phase II study, 39 healthy individuals from two US sites were randomly assigned to tasimelteon (10 [n=9], 20 [n=8], 50 [n=7], or 100 mg [n=7]) or placebo (n=8). We monitored individuals for 7 nights: 3 at baseline, 3 after a 5-h advance of sleep-wake schedule with treatment before sleep, and 1 after treatment; we measured plasma melatonin concentration for circadian phase assessment. In a phase III study, 411 healthy individuals from 19 US sites, who had transient insomnia induced in a sleep clinic by a 5-h advance of the sleep-wake schedule and a first-night effect in a sleep clinic, were given tasimelteon (20 [n=100], 50 [n=102], or 100 mg [n=106]) or placebo (n=103) 30 min before bedtime. Prespecified primary efficacy outcomes were polysomnographic sleep efficiency (phase II study), latency to persistent sleep (phase III study), and circadian phase shifting (phase II study). Analysis was by intention to treat. Safety was assessed in both studies. These trials are registered with ClinicalTrials.gov, numbers NCT00490945 and NCT00291187. Findings: In the phase II study, tasimelteon reduced sleep latency and increased sleep efficiency compared with placebo. The shift in plasma melatonin rhythm to an earlier hour was dose dependent. In the phase III study, tasimelteon improved sleep latency, sleep efficiency, and wake after sleep onset (ie, sleep maintenance). The frequency of adverse events was similar between tasimelteon and placebo. Interpretation: After an abrupt advance in sleep time, tasimelteon improved sleep initiation and maintenance concurrently with a shift in endogenous circadian rhythms. Tasimelteon may have therapeutic potential for transient insomnia in circadian rhythm sleep disorders.

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

Efficacy and evaluation of therapeutic exercises on adults with Parkinson's disease: a systematic review and network meta-analysis.

Background: Exercises are an effective treatment in Parkinson's disease (PD), but there is still controversy over which types should be used. We aimed to compare and rank the types of exercise that improve PD symptoms by quantifying information from randomised controlled trials. Methods: We performed a systematic review and network meta-analysis and searched PubMed, MEDLINE, Embase, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and China National Knowledge Infrastructure (CNKI) from their inception date to June 30, 2022. We included randomized controlled trials of 24 types of exercise for the interventional treatment of adults (≥ 50 years old) with PD. Effect size measures were standardized mean differences (SMDs) with 95% credible intervals (CrIs). The confidence of evidence was examined using Confidence in Network Meta-Analysis (CINeMA). Results: We identified 10 474 citations and included 250 studies involving 13 011 participants. Results of NMA showed that power training (PT) had the best benefits for motor symptoms compared with the control group (CON), with SMDs (95% CrI) (-1.46, [-2.18 to -0.74]). Body weight support treadmill training (BWS_TT) showed the best improvement in balance (1.55, [0.72 to 2.37]), gait velocity (1.15 [0.57 to 1.31]) and walking distance (1.96, [1.18 to 2.73]), and robotic assisted gait training (RA_GT) had the most benefits for freezing of gait (-1.09, [-1.80 to -0.38]). For non-motor symptoms, Dance showed the best benefits for depression (-1.71, [-2.79 to -0.73]). Only Yoga significantly reduced anxiety symptom compared with CON (-0.53, [0.96 to -0.11]). Only resistance training (RT) significantly enhanced sleep quality and cognition (-1.42, [-2.60 to -0.23]; 0.51, [0.09 to 0.94]). For muscle strength, PT showed the best advance (1.04, [0.64 to 1.44]). For concern of falling, five types of exercise were more effective than CON. Conclusions: There is low quality evidence that PT, Yoga, BWS_TT, Dance, and RT are the most effective treatments, pending outcome of interest, for adults with PD. Trial registration: PROSPERO (CRD42021220052).

BMC geriatrics · systematic review · 34 citationsread the source →

Non-invasive measurement of stress in dairy cows using infrared thermography.

The possibility that changes in eye temperature, measured using infrared thermography (IRT), can detect stress in dairy cattle was examined by six different stimulations of the stress axis. Six cows were given six treatments in a random Latin-square design: 1) Control (saline) 2) ACTH (0.05 mg Synacthen) 3) bCRH (20 mug) 4) bCRH (40 mug) 5) epinephrine (1.4 mug /kg liveweight) and 6) social isolation. Treatments were administered at time 0 and blood samples were taken at -30, -15, 0, 5, 10, 15, 20, 30, 40, 50, 60, 75, 90, 120, 180 and 240 min except for epinephrine which was sampled at -30, -15, -10, -5, 0, 2, 5, 10, 15, 20, 30, 45, 60, 90 and 120 min. Core body temperature was recorded every 10 min and eye images collected every 2 min. Eye temperature and cortisol increased following catheterization (P<0.05). ACTH increased following bCRH, cortisol increased following ACTH and bCRH (P<0.001) and NEFA increased following epinephrine (P<0.001). Core body temperature was unaffected by treatments. Eye temperature was unaffected by CRH and epinephrine but was higher 30 and 60 min following control and ACTH (P<0.001). Our results provide evidence that exogenous HPA stimulation does not increase eye temperature. The increases in eye temperature following catheterization however raise the possibility that a cognitive component may be required for an eye temperature response to occur.

Physiology & behavior · 137 citationsread the source →

The socioeconomic gradient in the incidence of stroke: a prospective study in middle-aged women in Sweden.

Background and purpose: A socioeconomic gradient in stroke has been demonstrated in a variety of settings, but mostly in men. Our purpose was to establish whether a socioeconomic gradient in stroke existed in a group of Swedish women and whether this gradient could be explained by established stroke risk factors or psychosocial factors. Methods: The Women's Lifestyle and Health Cohort Study includes 49 259 women from Sweden aged 30 to 50 years at baseline (1991 to 1992). The women completed an extensive questionnaire and were traced through linkages to national registries until the end of 2002. Among the 47 942 women included in these analyses, there were 200 cases of incident stroke during follow up (121 ischemic stroke, 47 hemorrhagic stroke, and 32 of unknown origin). Statistical analysis was through the Cox proportional hazards model. Results: The risk of stroke was significantly inversely related to years of education completed, our proxy for socioeconomic status (hazard ratio comparing lowest with highest education group=2.1, 95% CI: 1.4 to 2.9, P for trend <0.001). This association was reduced after adjustment for established risk factors, although remaining significant (1.5, 1.0 to 2.2, P for trend=0.04). The gradient was more pronounced for ischemic stroke (2.9, 1.8 to 4.7, P for trend <0.001) than for hemorrhagic stroke (1.4, 0.7 to 2.9, P for trend=0.35). Job strain and social support were unrelated to risk of stroke. Self-rated health was strongly related to risk of stroke mediated by established risk factors. Psychosocial factors did not contribute toward the socioeconomic gradient in stroke. Conclusions: There was a strong gradient in risk of stroke by years of education, especially for ischemic stroke. Most of the social gradient was explained by established risk factors, particularly smoking and alcohol, but not by psychosocial factors.

Stroke · 93 citationsread the source →

Sense of coherence and its relationship with oral health-related behaviour and knowledge of and attitudes towards oral health.

Objective: To investigate the relationship between sense of coherence (SOC), oral health-related behaviour, knowledge of and attitudes towards oral health in an adult Swedish population. Methods: A cross-sectional design with a stratified random sample of 910 individuals aged 20, 30, 40, 50, 60, 70 and 80 years were invited to the study, from Jönköping, Sweden. The investigation used the Swedish short version of the SOC questionnaire comprising 13 items and self-reported questions about oral health habits and knowledge of and attitudes towards oral health. In addition, a self-report questionnaire to elicit demographic information was included. Results: A total of 525 individuals, 261 men and 264 women, answered all the 13-item SOC questions, which constituted the final number of the participants. After adjustment for all the sociodemographic factors included in the analysis, individuals with a stronger SOC had twice as high a chance of having healthier behaviour, including a lower frequency of snacks and drinks between meals, as well as a more positive attitude, such as the importance of having one's own teeth as one gets older, satisfaction with their own teeth, perceiving their teeth as good and no feeling of dental fear, compared with individuals with a poorer SOC. Moreover, SOC and a good knowledge of caries were significantly associated after adjustment for age and gender. Conclusions: SOC was significantly associated with several oral health-related behaviours, attitudes towards oral health and knowledge of dental caries. When working with oral health promotion, SOC could be a way for promoting a better understanding of the behaviour and attitudes of individuals and for enabling dental personals to use that knowledge for the guidance of the individual.

Community dentistry and oral epidemiology · 45 citationsread the source →

Dapivirine vaginal ring for HIV prevention: modelling health outcomes, drug resistance and cost-effectiveness.

Introduction: A vaginal ring containing dapivirine is effective for HIV prevention as pre-exposure prophylaxis (PrEP). We evaluated the potential epidemiological impact and cost-effectiveness of dapivirine vaginal ring PrEP among 22- to 45-year-old women in KwaZulu-Natal, South Africa. Methods: Using mathematical modelling, we studied dapivirine vaginal ring PrEP implementation, either unprioritized, or prioritized based on HIV incidence (≥3% per year), age (22 to 29 years) or female sex worker status, alongside the implementation of voluntary medical male circumcision and antiretroviral therapy scaled-up to UNAIDS Fast-Track targets. Outcomes over the intervention (2019 to 2030) and lifetime horizons included cumulative HIV infections, life-years lived, costs and cost-effectiveness. We assessed the incremental cost-effectiveness ratios against the revealed willingness to pay ($500) and the standard (2017 per capita gross domestic product; $6161) cost-effectiveness thresholds for South Africa. Results: Compared to a reference scenario without PrEP, implementation of dapivirine vaginal ring PrEP, assuming 56% effectiveness and covering 50% of 22 to 29-year-old or high-incidence women, prevented 10% or 11% of infections by 2030 respectively. Equivalent, unprioritized coverage (30%) prevented fewer infections (7%), whereas 50% coverage of female sex workers had the least impact (4%). Drug resistance attributable to PrEP was modest (2% to 4% of people living with drug-resistant HIV). Over the lifetime horizon, dapivirine PrEP implementation among female sex workers was cost-saving, whereas incidence-based PrEP cost $1898 per life-year gained, relative to PrEP among female sex workers and $989 versus the reference scenario. In a scenario of 37% PrEP effectiveness, PrEP had less impact, but prioritization to female sex workers remained cost-saving. In uncertainty analysis, female sex worker PrEP was consistently cost-saving; and over the lifetime horizon, PrEP cost less than $6161 per life-year gained in over 99% of simulations, whereas incidence- and age-based PrEP cost below $500 per life-year gained in 61% and 49% of simulations respectively. PrEP adherence and efficacy, and the effectiveness of antiretroviral therapy for HIV prevention, were the principal drivers of uncertainty in the cost-effectiveness of PrEP. Conclusions: Dapivirine vaginal ring PrEP would be cost-saving in KwaZulu-Natal if prioritized to female sex workers. PrEP's impact on HIV prevention would be increased, with potential affordability, if prioritized to women by age or incidence.

Journal of the International AIDS Society · 20 citationsread the source →

A Novel Approach to Tackling Bullying in Schools: Personality-Targeted Intervention for Adolescent Victims and Bullies in Australia.

Objective: To examine the secondary effects of a personality-targeted intervention on bullying and harms among adolescent victims and bullies. Method: Outcomes were examined for victims and bullies in the Climate and Preventure study, Australia. Participants completed self-report measures at baseline and four follow-up assessments (6, 12, 24, and 36 months). Thirteen intervention schools (n = 1,087) received Preventure, a brief personality-targeted cognitive-behavioral therapy intervention for adolescents with high-risk personality types (hopelessness, anxiety sensitivity, impulsivity, sensation seeking). Thirteen control schools (n = 1,103) received health education as usual. Bullying was examined for high-risk victims (n = 143 in Preventure schools versus n = 153 in control schools) and bullies (n = 63 in Preventure schools versus n = 67 in control schools) in the total sample. Harms were examined for high-risk victims (n = 110 in Preventure schools versus n = 87 in control schools) and bullies (n = 50 in Preventure schools versus n = 30 in control schools) in independent schools. Results: There was no significant intervention effect for bullying victimization or perpetration in the total sample. In the subsample, mixed models showed greater reductions in victimization (b = -0.208, 95% CI -0.4104 to -0.002, p < .05), suicidal ideation (b = -0.130, 95% CI -0.225 to -0.034, p < .01), and emotional symptoms (b = -0.263, 95% CI -0.466 to -0.061, p < .05) among high-risk victims in Preventure versus control schools. Conduct problems (b = -0.292, 95% CI -0.554 to -0.030, p < .05) showed greater reductions among high-risk bullies in Preventure versus control schools, and suicidal ideation showed greater reductions among high-risk female bullies in Preventure versus control schools (b = -0.820, 95% CI -1.198 to -0.442, p < .001). Conclusion: The findings support targeting personality in bullying prevention. Clinical trial registration information: The CAP Study: Evaluating a Comprehensive Universal and Targeted Intervention Designed to Prevent Substance Use and Related Harms in Australian Adolescents; http://www.anzctr.org.au/; ACTRN12612000026820.

Journal of the American Academy of Child and Adolescent Psychiatry · 20 citationsread the source →

Balancing risks and benefits of cannabis use: umbrella review of meta-analyses of randomised controlled trials and observational studies.

Objective: To systematically assess credibility and certainty of associations between cannabis, cannabinoids, and cannabis based medicines and human health, from observational studies and randomised controlled trials (RCTs). Design: Umbrella review. Data sources: PubMed, PsychInfo, Embase, up to 9 February 2022. Eligibility criteria for selecting studies: Systematic reviews with meta-analyses of observational studies and RCTs that have reported on the efficacy and safety of cannabis, cannabinoids, or cannabis based medicines were included. Credibility was graded according to convincing, highly suggestive, suggestive, weak, or not significant (observational evidence), and by GRADE (Grading of Recommendations, Assessment, Development and Evaluations) (RCTs). Quality was assessed with AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). Sensitivity analyses were conducted. Results: 101 meta-analyses were included (observational=50, RCTs=51) (AMSTAR 2 high 33, moderate 31, low 32, or critically low 5). From RCTs supported by high to moderate certainty, cannabis based medicines increased adverse events related to the central nervous system (equivalent odds ratio 2.84 (95% confidence interval 2.16 to 3.73)), psychological effects (3.07 (1.79 to 5.26)), and vision (3.00 (1.79 to 5.03)) in people with mixed conditions (GRADE=high), improved nausea/vomit, pain, spasticity, but increased psychiatric, gastrointestinal adverse events, and somnolence among others (GRADE=moderate). Cannabidiol improved 50% reduction of seizures (0.59 (0.38 to 0.92)) and seizure events (0.59 (0.36 to 0.96)) (GRADE=high), but increased pneumonia, gastrointestinal adverse events, and somnolence (GRADE=moderate). For chronic pain, cannabis based medicines or cannabinoids reduced pain by 30% (0.59 (0.37 to 0.93), GRADE=high), across different conditions (n=7), but increased psychological distress. For epilepsy, cannabidiol increased risk of diarrhoea (2.25 (1.33 to 3.81)), had no effect on sleep disruption (GRADE=high), reduced seizures across different populations and measures (n=7), improved global impression (n=2), quality of life, and increased risk of somnolence (GRADE=moderate). In the general population, cannabis worsened positive psychotic symptoms (5.21 (3.36 to 8.01)) and total psychiatric symptoms (7.49 (5.31 to 10.42)) (GRADE=high), negative psychotic symptoms, and cognition (n=11) (GRADE=moderate). In healthy people, cannabinoids improved pain threshold (0.74 (0.59 to 0.91)), unpleasantness (0.60 (0.41 to 0.88)) (GRADE=high). For inflammatory bowel disease, cannabinoids improved quality of life (0.34 (0.22 to 0.53) (GRADE=high). For multiple sclerosis, cannabinoids improved spasticity, pain, but increased risk of dizziness, dry mouth, nausea, somnolence (GRADE=moderate). For cancer, cannabinoids improved sleep disruption, but had gastrointestinal adverse events (n=2) (GRADE=moderate). Cannabis based medicines, cannabis, and cannabinoids resulted in poor tolerability across various conditions (GRADE=moderate). Evidence was convincing from observational studies (main and sensitivity analyses) in pregnant women, small for gestational age (1.61 (1.41 to 1.83)), low birth weight (1.43 (1.27 to 1.62)); in drivers, car crash (1.27 (1.21 to 1.34)); and in the general population, psychosis (1.71 (1.47 to 2.00)). Harmful effects were noted for additional neonatal outcomes, outcomes related to car crash, outcomes in the general population including psychotic symptoms, suicide attempt, depression, and mania, and impaired cognition in healthy cannabis users (all suggestive to highly suggestive). Conclusions: Convincing or converging evidence supports avoidance of cannabis during adolescence and early adulthood, in people prone to or with mental health disorders, in pregnancy and before and while driving. Cannabidiol is effective in people with epilepsy. Cannabis based medicines are effective in people with multiple sclerosis, chronic pain, inflammatory bowel disease, and in palliative medicine but not without adverse events. Study registration: PROSPERO CRD42018093045. Funding: None.

BMJ (Clinical research ed.) · systematic review · 159 citationsread the source →

Engagement Strategies to Improve Adherence and Retention in Web-Based Mindfulness Programs: Systematic Review.

Background: Web-based mindfulness programs may be beneficial in improving the well-being outcomes of those living with chronic illnesses. Adherence to programs is a key indicator in improving outcomes; however, with the digitization of programs, it is necessary to enhance engagement and encourage people to return to digital health platforms. More information is needed on how engagement strategies have been used in web-based mindfulness programs to encourage adherence. Objective: The aim of this study is to develop a list of engagement strategies for web-based mindfulness programs and evaluate the impact of engagement strategies on adherence. Methods: A narrative systematic review was conducted across the MEDLINE Complete, CINAHL Complete, APA PsycINFO, and Embase databases and followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Articles were screened using the population, intervention, comparator, and outcome framework. Adults aged >18 years with chronic health conditions were included in the study. Mindfulness interventions, including those in combination with mindfulness-based cognitive therapy, delivered on the web through the internet or smartphone technology were included. Interventions lasted at least 2 weeks. Studies with a randomized controlled trial design or a pilot randomized controlled trial design were included. Engagement strategies, including web-based program features and facilitator-led strategies, adherence, and retention, were included. Results: A total of 1265 articles were screened, of which 19 were relevant and were included in the review. On average, 70.98% (2258/3181) of the study participants were women with a mean age of 46 (SD 13) years. Most commonly, mindfulness programs were delivered to people living with mental health conditions (8/19, 42%). Of the 19 studies, 8 (42%) used only program features to encourage adherence, 5 (26%) used facilitator-led strategies, and 6 (32%) used a combination of the two. Encouraging program adherence was the most common engagement strategy used, which was used in 77% (10/13) of the facilitator-led studies and 57% (8/14) of the program feature studies. Nearly two-thirds (63%) of the studies provided a definition of adherence, which varied between 50% and 100% completion across studies. The overall mean participant compliance to the mindfulness programs was 56% (SD 15%). Most studies (10/19, 53%) had a long-term follow-up, with the most common follow-up period being 12 weeks after intervention (3/10, 30%). After the intervention, the mean retention was 78% (SD 15%). Conclusions: Engagement strategies in web-based mindfulness programs comprise reminders to use the program. Other features may be suitable for encouraging adherence to interventions, and a facilitator-led component may result in higher retention. There is variance in the way adherence is measured, and intervention lengths and follow-up periods are inconsistent. More thorough reporting and a standardized framework for measuring adherence are needed to more accurately assess adherence and engagement strategies.

Journal of medical Internet research · systematic review · 45 citationsread the source →

Interventions for central serous chorioretinopathy: a network meta-analysis.

Background: Central serous chorioretinopathy (CSC) is characterized by serous detachment of the neural retina with dysfunction of the choroid and retinal pigment epithelium (RPE). The effects on the retina are usually self limited, although some people are left with irreversible vision loss due to progressive and permanent photoreceptor damage or RPE atrophy. There have been a variety of interventions used in CSC, including, but not limited to, laser treatment, photodynamic therapy (PDT), and intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents. However, it is not known whether these or other treatments offer significant advantages over observation or other interventions. At present there is no evidence-based consensus on the management of CSC. Due in large part to the propensity for CSC to resolve spontaneously or to follow a waxing and waning course, the most common initial approach to treatment is observation. It remains unclear whether this is the best approach with regard to safety and efficacy. Objectives: To compare the relative effectiveness of interventions for central serous chorioretinopathy. Search methods: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2014), EMBASE (January 1980 to October 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 October 2015. Selection criteria: Randomized controlled trials (RCTs) that compared any intervention for CSC with any other intervention for CSC or control. Data collection and analysis: Two review authors independently selected studies and extracted data. We pooled data from all studies using a fixed-effect model. For interventions applied to the eye (i.e. not systemic interventions), we synthesized direct and indirect evidence in a network meta-analysis model. Main results: We included 25 studies with 1098 participants (1098 eyes) and follow-up from 16 weeks to 12 years. Studies were conducted in Europe, North and South America, Middle East, and Asia. The trials were small (most trials enrolled fewer than 50 participants) and poorly reported; often it was unclear whether key aspects of the trial, such as allocation concealment, had been done. A substantial proportion of the trials were not masked. The studies considered a variety of treatments: anti-VEGF (ranibizumab, bevacizumab), PDT (full-dose, half-dose, 30%, low-fluence), laser treatment (argon, krypton and micropulse laser), beta-blockers, carbonic anhydrase inhibitors, Helicobactor pylori treatment, and nutritional supplements (Icaps, lutein); there were only one or two trials contributing data for each comparison. We downgraded for risk of bias and imprecision for most analyses, reflecting study limitations and imprecise estimates. Network meta-analysis (as planned in our protocol) did not help to resolve this uncertainty due to a lack of trials, and problems with intransitivity, particularly with respect to acute or chronic CSC.Low quality evidence from two trials suggested little difference in the effect of anti-VEGF (ranibizumab or bevacizumab) or observation on change in visual acuity at six months in acute CSC (mean difference (MD) 0.01 LogMAR (logarithm of the minimal angle of resolution), 95% confidence interval (CI) -0.02 to 0.03; 64 participants). CSC had resolved in all participants by six months. There were no significant adverse effects noted. Low quality evidence from one study (58 participants) suggested that half-dose PDT treatment of acute CSC probably results in a small improvement in vision (MD -0.10 logMAR, 95% CI -0.18 to -0.02), less recurrence (risk ratio (RR) 0.10, 95% CI 0.01 to 0.81) and less persistent CSC (RR 0.12, 95% CI 0.01 to 1.02) at 12 months compared to sham treatment. There were no significant adverse events noted. Low quality evidence from two trials (56 participants) comparing anti-VEGF to low-fluence PDT in chronic CSC found little evidence for any difference in visual acuity at 12 months (MD 0.03 logMAR, 95% CI -0.08 to 0.15). There was some evidence that more people in the anti-VEGF group had recurrent CSC compared to people treated with PDT but, due to inconsistency between trials, it was difficult to estimate an effect. More people in the anti-VEGF group had persistent CSC at 12 months (RR 6.19, 95% CI 1.61 to 23.81; 34 participants).Two small trials of micropulse laser, one in people with acute CSC and one in people with chronic CSC, provided low quality evidence that laser treatment may lead to better visual acuity (MD -0.20 logMAR, 95% CI -0.30 to -0.11; 45 participants). There were no significant adverse effects noted. Other comparisons were largely inconclusive. We identified 12 ongoing trials covering the following interventions: aflibercept and eplerenone in acute CSC; spironolactone, eplerenone, lutein, PDT, and micropulse laser in chronic CSC; and micropulse laser and oral mifepristone in two trials where type of CSC not clearly specified. Authors' conclusions: CSC remains an enigmatic condition in large part due to a natural history of spontaneous improvement in a high proportion of people and also because no single treatment has provided overwhelming evidence of efficacy in published RCTs. While a number of interventions have been proposed as potentially efficacious, the quality of study design, execution of the study and the relatively small number of participants enrolled and followed to revealing endpoints limits the utility of existing data. It is not clear whether there is a clinically important benefit to treating acute CSC which often resolves spontaneously as part of its natural history. RCTs comparing individual treatments to the natural history would be valuable in identifying potential treatment groups for head-to-head comparison. Of the interventions studied to date, PDT or micropulse laser treatment appear the most promising for study in future trials.

The Cochrane database of systematic reviews · systematic review · 74 citationsread the source →

Couple Interventions for Chronic Pain: A Systematic Review.

Objective: Couple interventions for chronic pain have been shown to more effectively reduce pain intensity for individuals with chronic pain (ICPs) than individual behavioral interventions or usual care. This systematic review identified randomized controlled trials of couple interventions to highlight strategies that could be incorporated into psychotherapy with ICPs and their romantic partners. Methods: The authors identified articles reporting randomized controlled trials of couple interventions for chronic pain. Three databases were searched (ie, PubMed, Embase, and PsycInfo), resulting in 18 studies and 22 articles. Results: Couple interventions resulted in statistically significant improvements in pain intensity compared with other conditions in 8% to 40% of the studies depending on the comparator group (i.e., control, individual intervention, another couple intervention), and in statistically significant improvements on a pain-related outcome compared with other conditions in 31% to 50% of the studies depending on the comparator group (ie, control, individual intervention, another couple intervention). Educating couples about pain was the most common strategy (83%). Jointly administered relaxation or meditation skills were included in nearly half of the interventions (48%). Many interventions taught cognitive-behavioral skills jointly to couples (39%) or to the ICP with partner encouragement (30%). Teaching couples how to request and provide assistance (30%), and encouraging partners to avoid reinforcing pain behaviors (39%), occurred frequently. ICPs and their partners were often asked to set goals (30%). Discussion: This review outlined strategies included in couple interventions for chronic pain that are derived from the cognitive-behavioral therapy, acceptance and commitment therapy, and operant behavioral traditions, but delivered relationally. Therapists working with ICPs and their partners may integrate these strategies into their practice to help couples who are managing chronic pain.

The Clinical journal of pain · systematic review · 12 citationsread the source →