Search the source libraries

Assessment of parasympathetic reactivation after exercise.

The objective of this study was to evaluate whether heart rate variability (HRV) can be used as an index of parasympathetic reactivation after exercise. Heart rate recovery after exercise has recently been shown to have prognostic significance and has been postulated to be related to abnormal recovery of parasympathetic tone. Ten normal subjects [5 men and 5 women; age 33 +/- 5 yr (mean +/- SE)] exercised to their maximum capacity, and 12 subjects (10 men and 2 women; age 61 +/- 10 yr) with coronary artery disease exercised for 16 min on two separate occasions, once in the absence of atropine and once with atropine (0.04 mg/kg) administered during exercise. The root mean square residual (RMS), which measures the deviation of the R-R intervals from a straight line, as well as the standard deviation (SD) and the root mean square successive difference of the R-R intervals (MSSD), were measured on successive 15-, 30-, and 60-s segments of a 5-min ECG obtained immediately after exercise. In recovery, the R-R interval was shorter with atropine (P < 0.0001). Without atropine, HRV, as measured by the MSSD and RMS, increased early in recovery from 4.1 +/- 0.4 and 3.7 +/- 0.4 ms in the first 15 s to 7.2 +/- 1.0 and 7.4 +/- 0.9 ms after 1 min, respectively (P < 0.0001). RMS (range 1.7-2.1 ms) and MSSD were less with atropine (P < 0.0001). RMS remained flat throughout recovery, whereas MSSD showed some decline over time from 3.0 to 2.2 ms (P < 0.002). RMS and MSSD were both directly related (r(2) = 0.47 and 0.56, respectively; P < 0.0001) to parasympathetic effect, defined as the difference in R-R interval without and with atropine. In conclusion, RMS and MSSD are parameters of HRV that can be used in the postexercise recovery period as indexes of parasympathetic reactivation after exercise. These tools may improve our understanding of parasympathetic reactivation after exercise and the prognostic significance of heart rate recovery.

American journal of physiology. Heart and circulatory physiology · clinical trial · 167 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 →

The prefrontal dysfunction in individuals with Internet gaming disorder: a meta-analysis of functional magnetic resonance imaging studies.

With the advancement in high-resolution magnetic resonance imaging (MRI) technology and automated analysis, studies on functional MRI (fMRI) made it possible to identify the functional activity of brain in vivo in individuals with Internet gaming disorder (IGD), and to explore the underpinning neuroscience basis of IGD. Yet, no available literature has systemically reviewed the fMRI studies of IGD using meta-analyses. This study reviewed 61 candidate articles and finally selected 10 qualified voxel-wise whole-brain analysis studies for performing a comprehensive series of meta-analyses employing effect size signed differential mapping approach. Compared with healthy controls, subjects with IGD showed a significant activation in the bilateral medial frontal gyrus (MFG) and the left cingulate gyrus, as well as the left medial temporal gyrus and fusiform gyrus. Furthermore, the on-line time of IGD subjects was positively correlated with activations in the left MFG and the right cingulated gyrus. These findings implicate the important role of dysfunctional prefrontal lobe in the neuropathological mechanism of IGD. Considering the overlapped role of prefrontal lobe in the reward and self-regulatory system, our results provided supportive evidence for the reclassification of IGD as a behavioural addiction.

Addiction biology · meta-analysis · 103 citationsread the source →

Lifestyle changes for treating psoriasis.

Background: Psoriasis is an inflammatory skin disease that presents with itching, red, scaling plaques; its worsening has been associated with obesity, drinking, smoking, lack of sleep, and a sedentary lifestyle. Lifestyle changes may improve psoriasis. Objectives: To assess the effects of lifestyle changes for psoriasis, including weight reduction, alcohol abstinence, smoking cessation, dietary modification, exercise, and other lifestyle change interventions. Search methods: We searched the following databases up to July 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched the China National Knowledge Infrastructure, the Airiti Library, and five trials registers up to July 2018. We checked the references of included trials for further relevant trials, and we asked the authors of the included trials if they were aware of any relevant unpublished data. Selection criteria: We included randomised controlled trials (RCTs) of lifestyle changes (either alone or in combination) for treating psoriasis in people diagnosed by a healthcare professional. Treatment had to be given for at least 12 weeks. Eligible comparisons were no lifestyle changes or another active intervention. Data collection and analysis: We used standard methodological procedures expected by Cochrane. The primary outcome measures were 'Severity of psoriasis' and 'Adherence to the intervention'. Secondary outcomes were 'Quality of life', 'Time to relapse', and 'Reduction in comorbidities'. We used GRADE to assess the quality of the evidence for each outcome. Main results: We included 10 RCTs with 1163 participants (mean age: 43 to 61 years; 656 men and 478 women were reported). Six trials examined the effects of dietary intervention (low-calorie diet) in 499 obese participants (mean age: 44.3 to 61 years; where reported, 395 had moderate-to-severe psoriasis). One trial assessed a combined dietary intervention and exercise programme in 303 obese participants with moderate-to-severe psoriasis who had started a systemic therapy for psoriasis and had not achieved clearance after four weeks of continuous treatment (median age: 53 years). Another trial assessed a walking exercise and continuous health education in 200 participants (mean age: 43.1 years, severity not reported). Finally, two trials included education programmes promoting a healthy lifestyle in 161 participants (aged 18 to 78 years), with one trial on mild psoriasis and the other trial not reporting severity. Comparisons included information only; no intervention; medical therapy alone; and usual care (such as continuing healthy eating).All trials were conducted in hospitals and treated participants for between 12 weeks and three years. One trial did not report the treatment period. Seven trials measured the outcomes at the end of treatment and there was no additional follow-up. In two trials, there was follow-up after the treatment ended. Five trials had a high risk of performance bias, and four trials had a high risk of attrition bias. We found no trials assessing interventions for alcohol abstinence or smoking cessation. No trials assessed time to relapse. Only two trials assessed adverse events; in one trial these were caused by the add-on therapy ciclosporin (given in both groups). The trial comparing two dietary interventions to a no-treatment group observed no adverse events. The results presented in this abstract are based on trials of obese participants. Outcomes for dietary interventions versus usual care were measured 24 weeks to six months from baseline. Compared to usual care, dietary intervention (strict caloric restriction) may lead to 75% or greater improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) (risk ratio (RR) 1.66, 95% confidence interval (CI) 1.07 to 2.58; 2 trials, 323 participants; low-quality evidence). Adherence to the intervention may be greater with the dietary intervention than usual care, but the 95% CI indicates that the dietary intervention might also make little or no difference (RR 1.26, 95% CI 0.76 to 2.09; 2 trials, 105 participants; low-quality evidence). Dietary intervention probably achieves a greater improvement in dermatology quality-of-life index (DLQI) score compared to usual care (MD -12.20, 95% CI -13.92 to -10.48; 1 trial, 36 participants; moderate-quality evidence), and probably reduces the BMI compared to usual care (MD -4.65, 95% CI -5.93 to -3.36; 2 trials, 78 participants; moderate-quality evidence).Outcomes for dietary interventions plus exercise programme were measured 16 weeks from baseline and are based on one trial (303 participants). Compared to information only (on reducing weight to improve psoriasis), combined dietary intervention and exercise programme (dietetic plan and physical activities) probably improves psoriasis severity, but the 95% CI indicates that the intervention might make little or no difference (PASI 75: RR 1.28, 95% CI 0.83 to 1.98). This combined intervention probably results in a greater reduction in BMI (median change -1.10 kg/m², P = 0.002), but there is probably no difference in adherence (RR 0.95, 95% CI 0.89 to 1.01; 137/151 and 145/152 participants adhered in the treatment and control group, respectively). There were no data on quality of life. These outcomes are based on moderate-quality evidence. Authors' conclusions: Dietary intervention may reduce the severity of psoriasis (low-quality evidence) and probably improves quality of life and reduces BMI (moderate-quality evidence) in obese people when compared with usual care, while combined dietary intervention and exercise programme probably improves psoriasis severity and BMI when compared with information only (moderate-quality evidence). None of the trials measured quality of life. We did not detect a clear difference in treatment adherence between those in the combined dietary intervention and exercise programme group and those given information only (moderate-quality evidence). Adherence may be improved through dietary intervention compared with usual care (low-quality evidence). Participants generally adhered well to the lifestyle interventions assessed in the review. No trials assessed the time to relapse. Trial limitations included unblinded participants and high dropout rate. Future trials should reduce dropouts and include comprehensive outcome measures; they should examine whether dietary intervention with or without an exercise programme is effective in non-obese people with psoriasis, whether an additional exercise programme is more effective than dietary intervention alone, whether the time to relapse prolongs in people who receive dietary intervention with or without exercise programme, and whether smoking cessation and alcohol abstinence are effective in treating psoriasis.

The Cochrane database of systematic reviews · systematic review · 48 citationsread the source →

Prostate-Specific Antigen-Based Screening for Prostate Cancer: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Prostate cancer is the second leading cause of cancer death among US men. Objective: To systematically review evidence on prostate-specific antigen (PSA)-based prostate cancer screening, treatments for localized prostate cancer, and prebiopsy risk calculators to inform the US Preventive Services Task Force. Data sources: Searches of PubMed, EMBASE, Web of Science, and Cochrane Registries and Databases from July 1, 2011, through July 15, 2017, with a surveillance search on February 1, 2018. Study selection: English-language reports of randomized clinical trials (RCTs) of screening; cohort studies reporting harms; RCTs and cohort studies of active localized cancer treatments vs conservative approaches (eg, active surveillance, watchful waiting); external validations of prebiopsy risk calculators to identify aggressive cancers. Data extraction and synthesis: One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality. Main outcomes and measures: Prostate cancer and all-cause mortality; false-positive screening results, biopsy complications, overdiagnosis; adverse effects of active treatments. Random-effects meta-analyses were conducted for treatment harms. Results: Sixty-three studies in 104 publications were included (N = 1 904 950). Randomization to PSA screening was not associated with reduced risk of prostate cancer mortality in either a US trial with substantial control group contamination (n = 76 683) or a UK trial with low adherence to a single PSA screen (n = 408 825) but was associated with significantly reduced prostate cancer mortality in a European trial (n = 162 243; relative risk [RR], 0.79 [95% CI, 0.69-0.91]; absolute risk reduction, 1.1 deaths per 10 000 person-years [95% CI, 0.5-1.8]). Of 61 604 men screened in the European trial, 17.8% received false-positive results. In 3 cohorts (n = 15 136), complications requiring hospitalization occurred in 0.5% to 1.6% of men undergoing biopsy after abnormal screening findings. Overdiagnosis was estimated to occur in 20.7% to 50.4% of screen-detected cancers. In an RCT of men with screen-detected prostate cancer (n = 1643), neither radical prostatectomy (hazard ratio [HR], 0.63 [95% CI, 0.21-1.93]) nor radiation therapy (HR, 0.51 [95% CI, 0.15-1.69]) were associated with significantly reduced prostate cancer mortality vs active monitoring, although each was associated with significantly lower risk of metastatic disease. Relative to conservative management, radical prostatectomy was associated with increased risk of urinary incontinence (pooled RR, 2.27 [95% CI, 1.82-2.84]; 3 trials; n = 1796) and erectile dysfunction (pooled RR, 1.82 [95% CI, 1.62-2.04]; 2 trials; n = 883). Relative to conservative management (8 cohort studies; n = 3066), radiation therapy was associated with increased risk of erectile dysfunction (pooled RR, 1.31 [95% CI, 1.20-1.42]). Conclusions and relevance: PSA screening may reduce prostate cancer mortality risk but is associated with false-positive results, biopsy complications, and overdiagnosis. Compared with conservative approaches, active treatments for screen-detected prostate cancer have unclear effects on long-term survival but are associated with sexual and urinary difficulties.

JAMA · systematic review · 353 citationsread the source →

Plasma free choline, betaine and cognitive performance: the Hordaland Health Study.

Choline and betaine are nutrients involved in one-carbon metabolism. Choline is essential for neurodevelopment and brain function. We studied the associations between cognitive function and plasma concentrations of free choline and betaine. In a cross-sectional study, 2195 subjects (55 % women), aged 70-74 years, underwent extensive cognitive testing including the Kendrick Object Learning Test (KOLT), Trail Making Test (part A, TMT-A), modified versions of the Digit Symbol Test (m-DST), Block Design (m-BD), Mini-Mental State Examination (m-MMSE) and Controlled Oral Word Association Test (COWAT). Compared with low concentrations, high choline (>8·4 μmol/l) was associated with better test scores in the TMT-A (56·0 v. 61·5, P=0·004), m-DST (10·5 v. 9·8, P=0·005) and m-MMSE (11·5 v. 11·4, P=0·01). A generalised additive regression model showed a positive dose-response relationship between the m-MMSE and choline (P=0·012 from a corresponding linear regression model). Betaine was associated with the KOLT, TMT-A and COWAT, but after adjustments for potential confounders, the associations lost significance. Risk ratios (RR) for poor test performance roughly tripled when low choline was combined with either low plasma vitamin B₁₂ (≤257 pmol/l) concentrations (RR(KOLT)=2·6, 95 % CI 1·1, 6·1; RR(m-MMSE)=2·7, 95 % CI 1·1, 6·6; RR(COWAT)=3·1, 95 % CI 1·4, 7·2) or high methylmalonic acid (MMA) (≥3·95 μmol/l) concentrations (RR(m-BD)=2·8, 95 % CI 1·3, 6·1). Low betaine (≤31·1 μmol/l) combined with high MMA was associated with elevated RR on KOLT (RR(KOLT)=2·5, 95 % CI 1·0, 6·2). Low plasma free choline concentrations are associated with poor cognitive performance. There were significant interactions between low choline or betaine and low vitamin B₁₂ or high MMA on cognitive performance.

The British journal of nutrition · cohort or longitudinal · 51 citationsread the source →

Multidisciplinary group rehabilitation versus individual physiotherapy for chronic nonspecific low back pain: a randomized trial.

Study design: A randomized trial. Objective: To evaluate the effectiveness of a semi-intensive multidisciplinary rehabilitation for patients with chronic low back pain in an outpatient setting. Summary and background data: Systematic reviews have shown that there is strong evidence that intensive multidisciplinary treatment (>100 hours), which includes functional restoration, improves function among chronic patients with low back pain, and moderate evidence that it reduces pain but contradictory evidence regarding improvement of working ability. However, there is paucity of data whether semi-intensive outpatient multidisciplinary rehabilitation in groups is more effective than individual physiotherapy. Materials and methods: A total of 120 women employed as healthcare and social care professionals with nonspecific chronic low back pain were recruited from two occupational healthcare centers. The patients were randomized into two intervention programs. Multidisciplinary rehabilitation (n = 59) was conducted in groups and comprised of physical training, workplace interventions, back school, relaxation training, and cognitive-behavioral stress management methods for 70 hours. The individual physiotherapy (n = 61) included physical exercise and passive treatment methods administered for 10 hours. Main outcome measures were: back pain and sciatic pain intensity, disability, sick leaves, healthcare consumption, symptoms of depression, and beliefs of working ability after 2 years. Results: There were no statistically significant differences between the two treatment groups in main outcome measures just after rehabilitation, at 6-, at 12-, or 24-month follow-up. In both intervention arms, however, the before-and-after comparison showed favorable effects, and the effects were still maintained at 2 years follow-up. Conclusions: The results of this study indicate that semilight outpatient multidisciplinary rehabilitation program for female chronic low back pain patients does not offer incremental benefits when compared with rehabilitation carried out by a physiotherapist having a cognitive-behavioral way of administering the treatment.

Spine · randomised controlled trial · 95 citationsread the source →

Intimate partner violence during pregnancy and perinatal mental disorders in low and lower middle income countries: A systematic review of literature, 1990-2017.

Mental health consequences of intimate partner violence (IPV) against pregnant and postpartum women are poorly understood in low and lower-middle-income countries (LLMIC). We systematically reviewed the evidence from 24 studies (1990-2017) selected via a comprehensive search strategy with 14 inclusion, exclusion, and quality-control criteria to assess the extent to which intimate partner violence during pregnancy adversely affects perinatal mental disorders among participants in 10 LLMIC across 4 economic regions. Mostly cross-sectional, studies included 61-1369 participants selected randomly (88%) or non-randomly (12%) from purposively selected 1-6 clinics or 1-50 communities. Multivariate logistic regression was most frequently used (68%) for association estimates, adjusting for 3-16 socio-demographic variables pertinent to: women; husbands; and/or households. The prevalence of physical IPV ranged 2-35% among participants; sexual IPV ranged 9-40%; and psychological IPV ranged 22-65%. The prevalence of antenatal and postnatal depression ranged 15-65% and 5-35% among participants, respectively. Suicidal ideation ranged 5-11% during pregnancy and 2-22% during the postpartum period. Study participants who had experienced IPV had 1.69-3.76 and 1.46-7.04 higher odds of antenatal and postnatal depression compared to those who had not, depending on country, and IPV type and severity. Considering the strong association between IPV and mental disorders, efforts should focus on developing IPV interventions aimed at preventing pregnancy during IPV and promoting mental health resilience among pregnancy and postpartum women in low and lower-middle-income countries.

Clinical psychology review · systematic review · 106 citationsread the source →

Skin Conductance Responses and Neural Activations During Fear Conditioning and Extinction Recall Across Anxiety Disorders.

Importance: The fear conditioning and extinction neurocircuitry has been extensively studied in healthy and clinical populations, with a particular focus on posttraumatic stress disorder. Despite significant overlap of symptoms between posttraumatic stress disorder and anxiety disorders, the latter has received less attention. Given that dysregulated fear levels characterize anxiety disorders, examining the neural correlates of fear and extinction learning may shed light on the pathogenesis of underlying anxiety disorders. Objectives: To investigate the psychophysiological and neural correlates of fear conditioning and extinction recall in anxiety disorders and to document how these features differ as a function of multiple diagnoses or anxiety severity. Design, setting, and participants: This investigation was a cross-sectional, case-control, functional magnetic resonance imaging study at an academic medical center. Participants were healthy controls and individuals with at least 1 of the following anxiety disorders: generalized anxiety disorder, social anxiety disorder, specific phobia, and panic disorder. The study dates were between March 2013 and May 2015. Exposures: Two-day fear conditioning and extinction paradigm. Main outcomes and measures: Skin conductance responses, blood oxygenation level-dependent responses, trait anxiety scores from the State Trait Anxiety Inventory-Trait Form, and functional connectivity. Results: This study included 21 healthy controls (10 women) and 61 individuals with anxiety disorders (36 women). P values reported for the neuroimaging results are all familywise error corrected. Skin conductance responses during extinction recall did not differ between individuals with anxiety disorders and healthy controls (ηp2 = 0.001, P = .79), where ηp2 is partial eta squared. The anxiety group had lower activation of the ventromedial prefrontal cortex (vmPFC) during extinction recall (ηp2 = 0.178, P = .02). A similar hypoactive pattern was found during early conditioning (ηp2 = 0.106, P = .009). The vmPFC hypoactivation was associated with anxiety symptom severity (r = -0.420, P = .01 for conditioning and r = -0.464, P = .004 for extinction recall) and the number of co-occuring anxiety disorders diagnosed (ηp2 = 0.137, P = .009 for conditioning and ηp2 = 0.227, P = .004 for extinction recall). Psychophysiological interaction analyses revealed that the fear network connectivity differed between healthy controls and the anxiety group during fear learning (ηp2 range between 0.088 and 0.176 and P range between 0.02 and 0.003) and extinction recall (ηp2 range between 0.111 and 0.235 and P range between 0.02 and 0.002). Conclusions and relevance: Despite no skin conductance response group differences during extinction recall, brain activation patterns between anxious and healthy individuals differed. These findings encourage future studies to examine the conditions longitudinally and in the context of treatment trials to improve and guide therapeutics via advanced neurobiological understanding of each disorder.

JAMA psychiatry · 104 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 →

Global, regional, and national mortality among young people aged 10-24 years, 1950-2019: a systematic analysis for the Global Burden of Disease Study 2019.

Background: Documentation of patterns and long-term trends in mortality in young people, which reflect huge changes in demographic and social determinants of adolescent health, enables identification of global investment priorities for this age group. We aimed to analyse data on the number of deaths, years of life lost, and mortality rates by sex and age group in people aged 10-24 years in 204 countries and territories from 1950 to 2019 by use of estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Methods: We report trends in estimated total numbers of deaths and mortality rate per 100 000 population in young people aged 10-24 years by age group (10-14 years, 15-19 years, and 20-24 years) and sex in 204 countries and territories between 1950 and 2019 for all causes, and between 1980 and 2019 by cause of death. We analyse variation in outcomes by region, age group, and sex, and compare annual rate of change in mortality in young people aged 10-24 years with that in children aged 0-9 years from 1990 to 2019. We then analyse the association between mortality in people aged 10-24 years and socioeconomic development using the GBD Socio-demographic Index (SDI), a composite measure based on average national educational attainment in people older than 15 years, total fertility rate in people younger than 25 years, and income per capita. We assess the association between SDI and all-cause mortality in 2019, and analyse the ratio of observed to expected mortality by SDI using the most recent available data release (2017). Findings: In 2019 there were 1·49 million deaths (95% uncertainty interval 1·39-1·59) worldwide in people aged 10-24 years, of which 61% occurred in males. 32·7% of all adolescent deaths were due to transport injuries, unintentional injuries, or interpersonal violence and conflict; 32·1% were due to communicable, nutritional, or maternal causes; 27·0% were due to non-communicable diseases; and 8·2% were due to self-harm. Since 1950, deaths in this age group decreased by 30·0% in females and 15·3% in males, and sex-based differences in mortality rate have widened in most regions of the world. Geographical variation has also increased, particularly in people aged 10-14 years. Since 1980, communicable and maternal causes of death have decreased sharply as a proportion of total deaths in most GBD super-regions, but remain some of the most common causes in sub-Saharan Africa and south Asia, where more than half of all adolescent deaths occur. Annual percentage decrease in all-cause mortality rate since 1990 in adolescents aged 15-19 years was 1·3% in males and 1·6% in females, almost half that of males aged 1-4 years (2·4%), and around a third less than in females aged 1-4 years (2·5%). The proportion of global deaths in people aged 0-24 years that occurred in people aged 10-24 years more than doubled between 1950 and 2019, from 9·5% to 21·6%. Interpretation: Variation in adolescent mortality between countries and by sex is widening, driven by poor progress in reducing deaths in males and older adolescents. Improving global adolescent mortality will require action to address the specific vulnerabilities of this age group, which are being overlooked. Furthermore, indirect effects of the COVID-19 pandemic are likely to jeopardise efforts to improve health outcomes including mortality in young people aged 10-24 years. There is an urgent need to respond to the changing global burden of adolescent mortality, address inequities where they occur, and improve the availability and quality of primary mortality data in this age group. Funding: Bill & Melinda Gates Foundation.

Lancet (London, England) · 199 citationsread the source →

Effectiveness of brief alcohol interventions in primary care populations.

Background: Excessive drinking is a significant cause of mortality, morbidity and social problems in many countries. Brief interventions aim to reduce alcohol consumption and related harm in hazardous and harmful drinkers who are not actively seeking help for alcohol problems. Interventions usually take the form of a conversation with a primary care provider and may include feedback on the person's alcohol use, information about potential harms and benefits of reducing intake, and advice on how to reduce consumption. Discussion informs the development of a personal plan to help reduce consumption. Brief interventions can also include behaviour change or motivationally-focused counselling. This is an update of a Cochrane Review published in 2007. Objectives: To assess the effectiveness of screening and brief alcohol intervention to reduce excessive alcohol consumption in hazardous or harmful drinkers in general practice or emergency care settings. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and 12 other bibliographic databases to September 2017. We searched Alcohol and Alcohol Problems Science Database (to December 2003, after which the database was discontinued), trials registries, and websites. We carried out handsearching and checked reference lists of included studies and relevant reviews. Selection criteria: We included randomised controlled trials (RCTs) of brief interventions to reduce hazardous or harmful alcohol consumption in people attending general practice, emergency care or other primary care settings for reasons other than alcohol treatment. The comparison group was no or minimal intervention, where a measure of alcohol consumption was reported. 'Brief intervention' was defined as a conversation comprising five or fewer sessions of brief advice or brief lifestyle counselling and a total duration of less than 60 minutes. Any more was considered an extended intervention. Digital interventions were not included in this review. Data collection and analysis: We used standard methodological procedures expected by Cochrane. We carried out subgroup analyses where possible to investigate the impact of factors such as gender, age, setting (general practice versus emergency care), treatment exposure and baseline consumption. Main results: We included 69 studies that randomised a total of 33,642 participants. Of these, 42 studies were added for this update (24,057 participants). Most interventions were delivered in general practice (38 studies, 55%) or emergency care (27 studies, 39%) settings. Most studies (61 studies, 88%) compared brief intervention to minimal or no intervention. Extended interventions were compared with brief (4 studies, 6%), minimal or no intervention (7 studies, 10%). Few studies targeted particular age groups: adolescents or young adults (6 studies, 9%) and older adults (4 studies, 6%). Mean baseline alcohol consumption was 244 g/week (30.5 standard UK units) among the studies that reported these data. Main sources of bias were attrition and lack of provider or participant blinding. The primary meta-analysis included 34 studies (15,197 participants) and provided moderate-quality evidence that participants who received brief intervention consumed less alcohol than minimal or no intervention participants after one year (mean difference (MD) -20 g/week, 95% confidence interval (CI) -28 to -12). There was substantial heterogeneity among studies (I² = 73%). A subgroup analysis by gender demonstrated that both men and women reduced alcohol consumption after receiving a brief intervention. We found moderate-quality evidence that brief alcohol interventions have little impact on frequency of binges per week (MD -0.08, 95% CI -0.14 to -0.02; 15 studies, 6946 participants); drinking days per week (MD -0.13, 95% CI -0.23 to -0.04; 11 studies, 5469 participants); or drinking intensity (-0.2 g/drinking day, 95% CI -3.1 to 2.7; 10 studies, 3128 participants).We found moderate-quality evidence of little difference in quantity of alcohol consumed when extended and no or minimal interventions were compared (-14 g/week, 95% CI -37 to 9; 6 studies, 1296 participants). There was little difference in binges per week (-0.08, 95% CI -0.28 to 0.12; 2 studies, 456 participants; moderate-quality evidence) or difference in days drinking per week (-0.45, 95% CI -0.81 to -0.09; 2 studies, 319 participants; moderate-quality evidence). Extended versus no or minimal intervention provided little impact on drinking intensity (9 g/drinking day, 95% CI -26 to 9; 1 study, 158 participants; low-quality evidence).Extended intervention had no greater impact than brief intervention on alcohol consumption, although findings were imprecise (MD 2 g/week, 95% CI -42 to 45; 3 studies, 552 participants; low-quality evidence). Numbers of binges were not reported for this comparison, but one trial suggested a possible drop in days drinking per week (-0.5, 95% CI -1.2 to 0.2; 147 participants; low-quality evidence). Results from this trial also suggested very little impact on drinking intensity (-1.7 g/drinking day, 95% CI -18.9 to 15.5; 147 participants; very low-quality evidence).Only five studies reported adverse effects (very low-quality evidence). No participants experienced any adverse effects in two studies; one study reported that the intervention increased binge drinking for women and two studies reported adverse events related to driving outcomes but concluded they were equivalent in both study arms. Sources of funding were reported by 67 studies (87%). With two exceptions, studies were funded by government institutes, research bodies or charitable foundations. One study was partly funded by a pharmaceutical company and a brewers association, another by a company developing diagnostic testing equipment. Authors' conclusions: We found moderate-quality evidence that brief interventions can reduce alcohol consumption in hazardous and harmful drinkers compared to minimal or no intervention. Longer counselling duration probably has little additional effect. Future studies should focus on identifying the components of interventions which are most closely associated with effectiveness.

The Cochrane database of systematic reviews · meta-analysis · 409 citationsread the source →

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

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

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

Childhood maltreatment and unfavourable clinical outcomes in bipolar disorder: a systematic review and meta-analysis.

Background: Bipolar disorder affects up to one in 25 individuals and identification of early risk indicators of negative outcomes could facilitate early detection of patients with greatest clinical needs and risk. We aimed to investigate the association between childhood maltreatment and key negative outcomes in patients with bipolar disorder. Methods: For this systematic review and meta-analysis we searched MEDLINE, PsycINFO, and Embase to identify articles published before Jan 1, 2015, examining the association of maltreatment (physical, sexual, or emotional abuse, neglect, or family conflict) before age 18 years with clinical features and course of illness in bipolar disorder. Data were extracted from published reports and any missing information was requested from investigators. We did 12 independent random-effects meta-analyses to quantify the associations between childhood maltreatment and course of illness or clinical features. Findings: We initially identified 527 records and after unsuitable studies were removed, our search yielded 148 publications of which 30 were used in the meta-analysis. Patients with bipolar disorder and history of childhood maltreatment had greater mania severity (six studies, 780 participants; odds ratio [OR] 2·02, 95% CI 1·21-3·39, p=0·008), greater depression severity (eight studies, 1007 participants; 1·57, 1·25-1·99, p=0·0001), greater psychosis severity (seven studies, 1494 participants; 1·49, 1·10-2·04, p=0·011), higher risk of comorbidity with post-traumatic stress disorder (eight studies, 2494 participants; 3·60, 2·45-5·30, p<0·0001), anxiety disorders (seven studies, 5091 participants; 1·90, 1·39-2·61, p<0·0001), substance misuse disorders (11 studies, 5469 participants; 1·84, 1·41-2·39, p<0·0001), alcohol misuse disorder (eight studies, 5040 participants; 1·44, 1·13-1·83, p=0·003), earlier age of bipolar disorder onset (14 studies, 5733 participants; 1·85, 1·43-2·40, p<0·0001), higher risk of rapid cycling (eight studies, 3010 participants; 1·89, 1·45-2·48, p<0·0001), greater number of manic episodes (seven studies, 3909 participants; 1·26, 1·09-1·47, p=0·003), greater number of depressive episodes (eight studies, 4025 participants; 1·38, 1·07-1·79, p=0·013), and higher risk of suicide attempt (13 studies, 3422 participants; 2·25, 1·88-2·70, p<0·0001) compared with those with bipolar disorder without childhood maltreatment. Overall, these associations were not explained by publication bias, undue effects of individual studies, or variation in study quality. Interpretation: Childhood maltreatment predicts unfavourable clinical features and course of illness in patients with bipolar disorder. Funding: None.

The lancet. Psychiatry · meta-analysis · 278 citationsread the source →

Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic.

Background: Before the COVID-19 pandemic, coronaviruses caused two noteworthy outbreaks: severe acute respiratory syndrome (SARS), starting in 2002, and Middle East respiratory syndrome (MERS), starting in 2012. We aimed to assess the psychiatric and neuropsychiatric presentations of SARS, MERS, and COVID-19. Methods: In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases (from their inception until March 18, 2020), and medRxiv, bioRxiv, and PsyArXiv (between Jan 1, 2020, and April 10, 2020) were searched by two independent researchers for all English-language studies or preprints reporting data on the psychiatric and neuropsychiatric presentations of individuals with suspected or laboratory-confirmed coronavirus infection (SARS coronavirus, MERS coronavirus, or SARS coronavirus 2). We excluded studies limited to neurological complications without specified neuropsychiatric presentations and those investigating the indirect effects of coronavirus infections on the mental health of people who are not infected, such as those mediated through physical distancing measures such as self-isolation or quarantine. Outcomes were psychiatric signs or symptoms; symptom severity; diagnoses based on ICD-10, DSM-IV, or the Chinese Classification of Mental Disorders (third edition) or psychometric scales; quality of life; and employment. Both the systematic review and the meta-analysis stratified outcomes across illness stages (acute vs post-illness) for SARS and MERS. We used a random-effects model for the meta-analysis, and the meta-analytical effect size was prevalence for relevant outcomes, I2 statistics, and assessment of study quality. Findings: 1963 studies and 87 preprints were identified by the systematic search, of which 65 peer-reviewed studies and seven preprints met inclusion criteria. The number of coronavirus cases of the included studies was 3559, ranging from 1 to 997, and the mean age of participants in studies ranged from 12·2 years (SD 4·1) to 68·0 years (single case report). Studies were from China, Hong Kong, South Korea, Canada, Saudi Arabia, France, Japan, Singapore, the UK, and the USA. Follow-up time for the post-illness studies varied between 60 days and 12 years. The systematic review revealed that during the acute illness, common symptoms among patients admitted to hospital for SARS or MERS included confusion (36 [27·9%; 95% CI 20·5-36·0] of 129 patients), depressed mood (42 [32·6%; 24·7-40·9] of 129), anxiety (46 [35·7%; 27·6-44·2] of 129), impaired memory (44 [34·1%; 26·2-42·5] of 129), and insomnia (54 [41·9%; 22·5-50·5] of 129). Steroid-induced mania and psychosis were reported in 13 (0·7%) of 1744 patients with SARS in the acute stage in one study. In the post-illness stage, depressed mood (35 [10·5%; 95% CI 7·5-14·1] of 332 patients), insomnia (34 [12·1%; 8·6-16·3] of 280), anxiety (21 [12·3%; 7·7-17·7] of 171), irritability (28 [12·8%; 8·7-17·6] of 218), memory impairment (44 [18·9%; 14·1-24·2] of 233), fatigue (61 [19·3%; 15·1-23·9] of 316), and in one study traumatic memories (55 [30·4%; 23·9-37·3] of 181) and sleep disorder (14 [100·0%; 88·0-100·0] of 14) were frequently reported. The meta-analysis indicated that in the post-illness stage the point prevalence of post-traumatic stress disorder was 32·2% (95% CI 23·7-42·0; 121 of 402 cases from four studies), that of depression was 14·9% (12·1-18·2; 77 of 517 cases from five studies), and that of anxiety disorders was 14·8% (11·1-19·4; 42 of 284 cases from three studies). 446 (76·9%; 95% CI 68·1-84·6) of 580 patients from six studies had returned to work at a mean follow-up time of 35·3 months (SD 40·1). When data for patients with COVID-19 were examined (including preprint data), there was evidence for delirium (confusion in 26 [65%] of 40 intensive care unit patients and agitation in 40 [69%] of 58 intensive care unit patients in one study, and altered consciousness in 17 [21%] of 82 patients who subsequently died in another study). At discharge, 15 (33%) of 45 patients with COVID-19 who were assessed had a dysexecutive syndrome in one study. At the time of writing, there were two reports of hypoxic encephalopathy and one report of encephalitis. 68 (94%) of the 72 studies were of either low or medium quality. Interpretation: If infection with SARS-CoV-2 follows a similar course to that with SARS-CoV or MERS-CoV, most patients should recover without experiencing mental illness. SARS-CoV-2 might cause delirium in a significant proportion of patients in the acute stage. Clinicians should be aware of the possibility of depression, anxiety, fatigue, post-traumatic stress disorder, and rarer neuropsychiatric syndromes in the longer term. Funding: Wellcome Trust, UK National Institute for Health Research (NIHR), UK Medical Research Council, NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London.

The lancet. Psychiatry · meta-analysis · 1531 citationsread the source →

Body mass index is negatively associated with telomere length: a collaborative cross-sectional meta-analysis of 87 observational studies.

Background: Even before the onset of age-related diseases, obesity might be a contributing factor to the cumulative burden of oxidative stress and chronic inflammation throughout the life course. Obesity may therefore contribute to accelerated shortening of telomeres. Consequently, obese persons are more likely to have shorter telomeres, but the association between body mass index (BMI) and leukocyte telomere length (TL) might differ across the life span and between ethnicities and sexes. Objective: A collaborative cross-sectional meta-analysis of observational studies was conducted to investigate the associations between BMI and TL across the life span. Design: Eighty-seven distinct study samples were included in the meta-analysis capturing data from 146,114 individuals. Study-specific age- and sex-adjusted regression coefficients were combined by using a random-effects model in which absolute [base pairs (bp)] and relative telomere to single-copy gene ratio (T/S ratio) TLs were regressed against BMI. Stratified analysis was performed by 3 age categories ("young": 18-60 y; "middle": 61-75 y; and "old": >75 y), sex, and ethnicity. Results: Each unit increase in BMI corresponded to a -3.99 bp (95% CI: -5.17, -2.81 bp) difference in TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -7.67 bp (95% CI: -10.03, -5.31 bp) difference. Each unit increase in BMI corresponded to a -1.58 × 10(-3) unit T/S ratio (0.16% decrease; 95% CI: -2.14 × 10(-3), -1.01 × 10(-3)) difference in age- and sex-adjusted relative TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -2.58 × 10(-3) unit T/S ratio (0.26% decrease; 95% CI: -3.92 × 10(-3), -1.25 × 10(-3)). The associations were predominantly for the white pooled population. No sex differences were observed. Conclusions: A higher BMI is associated with shorter telomeres, especially in younger individuals. The presently observed difference is not negligible. Meta-analyses of longitudinal studies evaluating change in body weight alongside change in TL are warranted.

The American journal of clinical nutrition · meta-analysis · 139 citationsread the source →

Antenatal breastfeeding education for increasing breastfeeding duration.

Background: Breast milk is well recognised as the best food source for infants. The impact of antenatal breastfeeding (BF) education on the duration of BF has not been evaluated. Objectives: To assess the effectiveness of antenatal breastfeeding (BF) education for increasing BF initiation and duration. Search methods: We searched Cochrane Pregnancy and Childbirth's Trials Register on 1 March 2016, CENTRAL (The Cochrane Library, 2016, Issue 3), MEDLINE (1966 to 1 March 2016) and Scopus (January 1985 to 1 March 2016). We contacted experts and searched reference lists of retrieved articles. Selection criteria: All identified published, unpublished and ongoing randomised controlled trials (RCTs) assessing the effect of formal antenatal BF education or comparing two different methods of formal antenatal BF education, on the duration of BF. We included RCTs that only included antenatal interventions and excluded those that combined antenatal and intrapartum or postpartum BF education components. Cluster-randomised trials were included in this review. Quasi-randomised trials were not eligible for inclusion. Data collection and analysis: We assessed all potential studies identified as a result of the search strategy. Two review authors extracted data from each included study using the agreed form and assessed risk of bias. We resolved discrepancies through discussion. We assessed the quality of the evidence using the GRADE approach. Main results: This review update includes 24 studies (10,056 women). Twenty studies (9789 women) contribute data to analyses. Most studies took place in high-income countries such as the USA, UK, Canada and Australia. In the first five comparisons, we display the included trials according to type of intervention without pooling data. For the 'Summary of findings' we pooled data for a summary effect. Five included studies were cluster-randomised trials: all of these adjusted data and reported adjustments as odds ratios (OR). We have analysed the data using the generic inverse variance method and presented results as odds ratios, because we were unable to derive a cluster-adjusted risk ratio from the published cluster-trial. We acknowledge that the use of odds ratio prevents the pooling of these cluster trials in our main analyses. One method of BF education with standard (routine) careThere were no group differences for duration of any BF in days or weeks. There was no evidence that interventions improved the proportion of women with any BF or exclusive BF at three or six months. Single trials of different interventions were unable to show that education improved initiation of BF, apart from one small trial at high risk of attrition bias. Many trial results marginally favoured the intervention but had wide confidence intervals crossing the line of no effect. BF complications such as mastitis and other BF problems were similar in treatment arms in single trials reporting these outcomes. Multiple methods of BF education versus standard careFor all trials included in this comparison we have presented the cluster-adjusted odds ratios as reported in trial publications. One three-arm study found the intervention of BF booklet plus video plus Lactation Consultant versus standard care improved the proportion of women exclusively BF at three months (OR 2.60, 95% CI 1.25 to 5.40; women = 159) and marginally at six months (OR 2.40, 95% CI 1.00 to 5.76; women = 175). For the same trial, an intervention arm without a lactation consultant but with the BF booklet and video did not have the same effect on proportion of women exclusively BF at three months (OR 1.80, 95% CI 0.80 to 4.05; women = 159) or six months (OR 0.90, 95% CI 0.30 to 2.70; women = 184). One study compared monthly BF sessions and weekly cell phone message versus standard care and reported improvements in the proportion of women exclusively BF at both three and six months (three months OR 1.80, 95% CI 1.10 to 2.95; women = 390; six months OR 2.40, 95% CI 1.40 to 4.11; women = 390). One study found monthly BF sessions and weekly cell phone messages improved initiation of BF over standard care (OR 2.61, 95% CI 1.61 to 4.24; women = 380). BF education session versus standard care, pooled analyses for 'Summary of findings' (SoF)This comparison does not include cluster-randomised trials reporting adjusted odds ratios. We did not downgrade any evidence for trials' lack of blinding; no trial had adequate blinding of staff and participants. The SoF table presents risk ratios for all outcomes analysed. For proportion of women exclusively BF there is no evidence that antenatal BF education improved BF at three months (RR 1.06, 95% CI 0.90 to 1.25; women = 822; studies = 3; moderate quality evidence) or at six months (RR 1.07, 95% CI 0.87 to 1.30; women = 2161; studies = 4; moderate quality evidence). For proportion of women with any BF there were no group differences in BF at three (average RR 0.98, 95% CI 0.82 to 1.18; women = 654; studies = 2; I² = 60%; low-quality evidence) or six months (average RR 1.05, 95% CI 0.90 to 1.23; women = 1636; studies = 4; I² = 61%; high-quality evidence). There was no evidence that antenatal BF education could improve initiation of BF (average RR 1.01, 95% CI 0.94 to 1.09; women = 3505; studies = 8; I² = 69%; high-quality evidence). Where we downgraded evidence this was due to small sample size or wide confidence intervals crossing the line of no effect, or both. There was insufficient data for subgroup analysis of mother's occupation or education. Authors' conclusions: There was no conclusive evidence supporting any antenatal BF education for improving initiation of BF, proportion of women giving any BF or exclusively BF at three or six months or the duration of BF. There is an urgent need to conduct a high-quality, randomised controlled study to evaluate the effectiveness and adverse effects of antenatal BF education, especially in low- and middle-income countries. Evidence in this review is primarily relevant to high-income settings.

The Cochrane database of systematic reviews · meta-analysis · 86 citationsread the source →

Adverse events associated with medium- and long-term use of opioids for chronic non-cancer pain: an overview of Cochrane Reviews.

Background: Chronic pain is common and can be challenging to manage. Despite increased utilisation of opioids, the safety and efficacy of long-term use of these compounds for chronic non-cancer pain (CNCP) remains controversial. This overview of Cochrane Reviews complements the overview entitled 'High-dose opioids for chronic non-cancer pain: an overview of Cochrane Reviews'. Objectives: To provide an overview of the occurrence and nature of adverse events associated with any opioid agent (any dose, frequency, or route of administration) used on a medium- or long-term basis for the treatment of CNCP in adults. Methods: We searched the Cochrane Database of Systematic Reviews (the Cochrane Library) Issue 3, 2017 on 8 March 2017 to identify all Cochrane Reviews of studies of medium- or long-term opioid use (2 weeks or more) for CNCP in adults aged 18 and over. We assessed the quality of the reviews using the AMSTAR criteria (Assessing the Methodological Quality of Systematic Reviews) as adapted for Cochrane Overviews. We assessed the quality of the evidence for the outcomes using the GRADE framework. Main results: We included a total of 16 reviews in our overview, of which 14 presented unique quantitative data. These 14 Cochrane Reviews investigated 14 different opioid agents that were administered for time periods of two weeks or longer. The longest study was 13 months in duration, with most in the 6- to 16-week range. The quality of the included reviews was high using AMSTAR criteria, with 11 reviews meeting all 10 criteria, and 5 of the reviews meeting 9 out of 10, not scoring a point for either duplicate study selection and data extraction, or searching for articles irrespective of language and publication type. The quality of the evidence for the generic adverse event outcomes according to GRADE ranged from very low to moderate, with risk of bias and imprecision being identified for the following generic adverse event outcomes: any adverse event, any serious adverse event, and withdrawals due to adverse events. A GRADE assessment of the quality of the evidence for specific adverse events led to a downgrading to very low- to moderate-quality evidence due to risk of bias, indirectness, and imprecision. We calculated the equivalent milligrams of morphine per 24 hours for each opioid studied (buprenorphine, codeine, dextropropoxyphene, dihydrocodeine, fentanyl, hydromorphone, levorphanol, methadone, morphine, oxycodone, oxymorphone, tapentadol, tilidine, and tramadol). In the 14 Cochrane Reviews providing unique quantitative data, there were 61 studies with a total of 18,679 randomised participants; 12 of these studies had a cross-over design with two to four arms and a total of 796 participants. Based on the 14 selected Cochrane Reviews, there was a significantly increased risk of experiencing any adverse event with opioids compared to placebo (risk ratio (RR) 1.42, 95% confidence interval (CI) 1.22 to 1.66) as well as with opioids compared to a non-opioid active pharmacological comparator, with a similar risk ratio (RR 1.21, 95% CI 1.10 to 1.33). There was also a significantly increased risk of experiencing a serious adverse event with opioids compared to placebo (RR 2.75, 95% CI 2.06 to 3.67). Furthermore, we found significantly increased risk ratios with opioids compared to placebo for a number of specific adverse events: constipation, dizziness, drowsiness, fatigue, hot flushes, increased sweating, nausea, pruritus, and vomiting. There was no data on any of the following prespecified adverse events of interest in any of the included reviews in this overview of Cochrane Reviews: addiction, cognitive dysfunction, depressive symptoms or mood disturbances, hypogonadism or other endocrine dysfunction, respiratory depression, sexual dysfunction, and sleep apnoea or sleep-disordered breathing. We found no data for adverse events analysed by sex or ethnicity. Authors' conclusions: A number of adverse events, including serious adverse events, are associated with the medium- and long-term use of opioids for CNCP. The absolute event rate for any adverse event with opioids in trials using a placebo as comparison was 78%, with an absolute event rate of 7.5% for any serious adverse event. Based on the adverse events identified, clinically relevant benefit would need to be clearly demonstrated before long-term use could be considered in people with CNCP in clinical practice. A number of adverse events that we would have expected to occur with opioid use were not reported in the included Cochrane Reviews. Going forward, we recommend more rigorous identification and reporting of all adverse events in randomised controlled trials and systematic reviews on opioid therapy. The absence of data for many adverse events represents a serious limitation of the evidence on opioids. We also recommend extending study follow-up, as a latency of onset may exist for some adverse events.

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

Home-based multidimensional survivorship programmes for breast cancer survivors.

Background: The prognosis and survival rate of women with breast cancer have significantly improved worldwide. Effective home-based multidimensional programmes for breast cancer survivors have gained an ever greater emphasis in survivorship care to maximise women's quality of life for their successful transition to rehabilitation and normal life. It is important to summarise the best available evidence to evaluate the effects of home-based multidimensional survivorship programmes on quality of life in women within 10 years of the completion of surgery or adjuvant cancer therapy for breast cancer, or both. Objectives: To assess the effects of home-based, multidimensional survivorship (HBMS) programmes on maintaining or improving the quality of life in breast cancer survivors. Search methods: In April 2016 we searched the Cochrane Breast Cancer Specialised Register, CENTRAL, PubMed, Embase, CINAHL Plus, PsycINFO, Web of Science, and the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov. We also screened reference lists of all identified studies and contacted study authors. Selection criteria: Randomised controlled trials (RCTs) and quasi-RCTs assessing the effects of HBMS programmes in maintaining or improving quality of life in women with stages 0 to 3 breast cancer who completed primary cancer treatment (surgery or adjuvant cancer therapy, or both) up to 10 years earlier. We considered studies where the interventions included more than one of the following listed components: educational (such as information provision and self-management advice), physical (such as exercise training and resistance training) and psychological (such as counselling and cognitive therapies), to constitute a multidimensional programme. Interventions had to be allowed to be carried out at home. Data collection and analysis: Two authors independently assessed eligible studies for inclusion, and performed quality assessment and extracted relevant data of the included studies. Quality of life was the primary outcome of the review. Main results: We included 22 RCTs and four quasi-RCTs on 2272 participants. We categorised the intervention components into four groups: educational and psychological; educational and physical; physical and psychological; and educational, physical and psychological. Most of the studies used usual care (routine medical follow-up services) as the comparator. A few studies used a lower level or different type of intervention (e.g. stress management or exercise) or attention control as the comparator. We used the Functional Assessment of Cancer Therapy-Breast (FACT B), European Organisation for Research and Treatment of Cancer Quality of Life C30 (EORTC C30), Quality of Life (QoL) Breast Cancer, and SF36 questionnaires to assess quality of life. HBMS programmes may increase breast cancer-specific quality of life and global quality of life immediately after the intervention, as measured by FACT-B and EORTC C30 (FACT-B: mean difference (MD) 4.55, 95% confidence interval (CI) 2.33 to 6.78, 7 studies, 764 participants; EORTC: MD 4.38, 95% CI 0.11 to 8.64, 6 studies; 299 participants; moderate-quality evidence). There was no evidence of a difference in quality of life as measured by QoL-Breast Cancer or SF-36 (QoL-Breast Cancer: MD 0.42, 95% CI -0.02 to 0.85, 2 studies, 111 participants, very low-quality evidence; physical composite score SF36: MD 0.55, 95% CI -3.52 to 4.63, 2 studies, 308 participants, low-quality evidence).We observed a similar pattern at one to three months after the intervention: FACT-B (MD 6.10, 95% CI 2.48 to 9.72, 2 studies, 426 participants), EORTC-C30 (MD 6.32, 95% CI 0.61 to 12.04, 2 studies; 172 participants) and QoL-Breast Cancer (MD 0.45, 95% CI -0.19 to 1.09, 1 study, 61 participants). At four to six months and 12 months, there was no evidence of a difference in quality of life between groups (four to six months: EORTC - MD 0.08, 95% CI -7.28 to 7.44, 2 studies; 117 participants; SF-36 - MD -1.05, 95% CI -5.60 to 3.51, 2 studies, 308 participants; 12 months: EORTC - MD 2.04, 95% CI -9.91 to 13.99, 1 study; 57 participants).Functional status was incorporated into the quality of life subscale findings. HBMS programmes may decrease anxiety (MD of Hospital Anxiety and Depression Scale (HADS) -1.01, 95% CI -1.94 to -0.08, 5 studies, 253 participants, low-quality evidence) compared to control immediately after the intervention but the effect did not persist at four to six months. There was no evidence of improvements in depression immediately after HBMS (MD of HADS -1.36, 95% CI -2.94 to 0.22, 4 studies, 213 participants, low-quality evidence) or at follow-up. HBMS programmes may also decrease fatigue (MD -1.11, 95% CI -1.78 to -0.45, 3 studies, 127 participants; low-quality evidence) and insomnia (MD -1.81, 95% CI -3.34 to -0.27, 3 studies, 185 participants, low-quality evidence).None of the included studies reported service needs and utilisation and cost of care, and therefore the effect of HBMS programmes on healthcare utilisation and cost is unknown. Due to the variations in assessment methods of adherence among the eight studies, we could not combine the results for meta-analysis. We synthesised the results narratively, with the reported adherence rates of 58% to 100%. Authors' conclusions: The results of this systematic review and meta-analysis revealed that HBMS programmes in breast cancer survivors appear to have a short-term beneficial effect of improving breast cancer-specific quality of life and global quality of life as measured by FACT-B and EORTC-C30, respectively. In addition, HBMS programmes are associated with a reduction in anxiety, fatigue and insomnia immediately after the intervention. We assessed the quality of evidence across studies as moderate for some outcomes, meaning that we are fairly confident about the results, while we assessed other outcomes as being low-quality, meaning that we are uncertain about the result.

The Cochrane database of systematic reviews · meta-analysis · 59 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 →

Stigma reduction interventions for children and adolescents in low- and middle-income countries: Systematic review of intervention strategies.

Stigmatisation and discrimination are common worldwide, and have profound negative impacts on health and quality of life. Research, albeit limited, has focused predominantly on adults. There is a paucity of literature about stigma reduction strategies concerning children and adolescents, with evidence especially sparse for low- and middle-income countries (LMIC). This systematic review synthesised child-focused stigma reduction strategies in LMIC, and compared these to adult-focused interventions. Relevant publications were systematically searched in July and August 2018 in the following databases; Cochrane, Embase, Global Health, HMIC, Medline, PsycINFO, PubMed and WorldWideScience.org, and through Google Custom Search. Included studies and identified reviews were cross-referenced. Three categories of search terms were used: (i) stigma, (ii) intervention, and (iii) LMIC settings. Data on study design, participants and intervention details including strategies and implementation factors were extracted. Within 61 unique publications describing 79 interventions, utilising 14 unique stigma reduction strategies, 14 papers discussed 21 interventions and 10 unique strategies involving children. Most studies targeted HIV/AIDS (50% for children, 38% for adults) or mental illness (14% vs 34%) stigma. Community education (47%), individual empowerment (15%) and social contact (12%) were most employed in child-focused interventions. Most interventions were implemented at one socio-ecological level; child-focused interventions mostly employed community-level strategies (88%). Intervention duration was mostly short; between half a day and a week. Printed or movie-based material was key to deliver child-focused interventions (37%), while professionals most commonly implemented adult-focused interventions (53%). Ten unique, child-focused strategies were all evaluated positively, using a diverse set of scales. Children and adolescents are under-represented in stigma reduction in LMIC. More stigma reduction interventions in LMIC, addressing a wider variety of stigmas, with children as direct and indirect target group, are needed. This systematic review is registered under International Prospective Register of Systematic Reviews PROSPERO, reference number #CRD42018094700.

Social science & medicine (1982) · systematic review · 77 citationsread the source →

Advance care planning beyond advance directives: perspectives from patients and surrogates.

Context: Advance care planning (ACP) has focused on documenting life-sustaining treatment preferences in advance directives (ADs). The ADs alone may be insufficient to prepare diverse patients and surrogates for complex medical decisions. Objectives: To understand what steps best prepare patients and surrogates for decision making. Methods: We conducted 13 English/Spanish focus groups with participants from a Veterans Affairs and county hospital and the community. Seven groups included patients (n=38), aged ≥65 years, who reported making serious medical decisions. Six separate groups included surrogates (n=31), aged ≥18 years, who made decisions for others. Semistructured focus groups asked what activities best prepared the participants for decision making. Two investigators independently coded data and performed thematic content analysis. Disputes were resolved by consensus. Results: The mean±SD patient age was 78±8 years, and 61% were nonwhite. The mean±SD surrogate age was 57±10 years, and 91% were nonwhite. Qualitative analysis identified four overarching themes about how to best prepare for decision making: 1) identify values based on past experiences and quality of life, 2) choose surrogates wisely and verify that they understand their role, 3) decide whether to grant leeway in surrogate decision making, and 4) inform other family and friends of one's wishes to prevent conflict. Conclusion: Beyond ADs, patients and surrogates recommend several additional steps to prepare for medical decision making including using past experiences to identify values, verifying that the surrogate understands their role, deciding whether to grant surrogates leeway, and informing other family and friends of one's wishes. Future ACP interventions should consider incorporating these additional ACP activities.

Journal of pain and symptom management · cohort or longitudinal · 142 citationsread the source →

Harms of Breast Cancer Screening: Systematic Review to Update the 2009 U.S. Preventive Services Task Force Recommendation.

Background: In 2009, the U.S. Preventive Services Task Force recommended biennial mammography screening for women aged 50 to 74 years and selective screening for those aged 40 to 49 years. Purpose: To review studies of screening in average-risk women with mammography, magnetic resonance imaging, or ultrasonography that reported on false-positive results, overdiagnosis, anxiety, pain, and radiation exposure. Data sources: MEDLINE and Cochrane databases through December 2014. Study selection: English-language systematic reviews, randomized trials, and observational studies of screening. Data extraction: Investigators extracted and confirmed data from studies and dual-rated study quality. Discrepancies were resolved through consensus. Data synthesis: Based on 2 studies of U.S. data, 10-year cumulative rates of false-positive mammography results and biopsies were higher with annual than biennial screening (61% vs. 42% and 7% vs. 5%, respectively) and for women aged 40 to 49 years, those with dense breasts, and those using combination hormone therapy. Twenty-nine studies using different methods reported overdiagnosis rates of 0% to 54%; rates from randomized trials were 11% to 22%. Women with false-positive results reported more anxiety, distress, and breast cancer-specific worry, although results varied across 80 observational studies. Thirty-nine observational studies indicated that some women reported pain during mammography (1% to 77%); of these, 11% to 46% declined future screening. Models estimated 2 to 11 screening-related deaths from radiation-induced cancer per 100,000 women using digital mammography, depending on age and screening interval. Five observational studies of tomosynthesis and mammography indicated increased biopsies but reduced recalls compared with mammography alone. Limitations: Studies of overdiagnosis were highly heterogeneous, and estimates varied depending on the analytic approach. Studies of anxiety and pain used different outcome measures. Radiation exposure was based on models. Conclusion: False-positive results are common and are higher for annual screening, younger women, and women with dense breasts. Although overdiagnosis, anxiety, pain, and radiation exposure may cause harm, their effects on individual women are difficult to estimate and vary widely. Primary funding source: Agency for Healthcare Research and Quality.

Annals of internal medicine · systematic review · 267 citationsread the source →

The Use of Facebook in Recruiting Participants for Health Research Purposes: A Systematic Review.

Background: Social media is a popular online tool that allows users to communicate and exchange information. It allows digital content such as pictures, videos and websites to be shared, discussed, republished and endorsed by its users, their friends and businesses. Adverts can be posted and promoted to specific target audiences by demographics such as region, age or gender. Recruiting for health research is complex with strict requirement criteria imposed on the participants. Traditional research recruitment relies on flyers, newspaper adverts, radio and television broadcasts, letters, emails, website listings, and word of mouth. These methods are potentially poor at recruiting hard to reach demographics, can be slow and expensive. Recruitment via social media, in particular Facebook, may be faster and cheaper. Objective: The aim of this study was to systematically review the literature regarding the current use and success of Facebook to recruit participants for health research purposes. Methods: A literature review was completed in March 2017 in the English language using MEDLINE, EMBASE, Web of Science, PubMed, PsycInfo, Google Scholar, and a hand search of article references. Papers from the past 12 years were included and number of participants, recruitment period, number of impressions, cost per click or participant, and conversion rate extracted. Results: A total of 35 studies were identified from the United States (n=22), Australia (n=9), Canada (n=2), Japan (n=1), and Germany (n=1) and appraised using the Critical Appraisal Skills Programme (CASP) checklist. All focused on the feasibility of recruitment via Facebook, with some (n=10) also testing interventions, such as smoking cessation and depression reduction. Most recruited young age groups (16-24 years), with the remaining targeting specific demographics, for example, military veterans. Information from the 35 studies was analyzed with median values being 264 recruited participants, a 3-month recruitment period, 3.3 million impressions, cost per click of US $0.51, conversion rate of 4% (range 0.06-29.50), eligibility of 61% (range 17-100), and cost per participant of US $14.41. The studies showed success in penetrating hard to reach populations, finding the results representative of their control or comparison demographic, except for an over representation of young white women. Conclusions: There is growing evidence to suggest that Facebook is a useful recruitment tool and its use, therefore, should be considered when implementing future health research. When compared with traditional recruitment methods (print, radio, television, and email), benefits include reduced costs, shorter recruitment periods, better representation, and improved participant selection in young and hard to reach demographics. It however, remains limited by Internet access and the over representation of young white women. Future studies should recruit across all ages and explore recruitment via other forms of social media.

Journal of medical Internet research · systematic review · 503 citationsread the source →

Pharmacological and psychotherapeutic interventions for management of obsessive-compulsive disorder in adults: a systematic review and network meta-analysis.

Background: Several interventions are available for management of obsessive-compulsive disorder in adults, but few studies have compared their relative efficacy in a single analysis. We aimed to simultaneously compare all available treatments using both direct and indirect data. Methods: In this systematic review and network meta-analysis, we searched the two controlled trials registers maintained by the Cochrane Collaboration Common Mental Disorders group for trials published up to Feb 16, 2016. We selected randomised controlled trials in which an active psychotherapeutic or pharmacological intervention had been used in adults with obsessive-compulsive disorder. We allowed all comorbidities except for schizophrenia or bipolar disorder. We excluded studies that focused exclusively on treatment-resistant patient populations defined within the same study. We extracted data from published reports. The primary outcome was symptom severity as measured by the Yale-Brown Obsessive Compulsive Scale. We report mean differences with 95% credible intervals compared with placebo. This study is registered with PROSPERO, number CRD42012002441. Findings: We identified 1480 articles in our search and included 53 articles (54 trials; 6652 participants) in the network meta-analysis. Behavioural therapy (mean difference -14·48 [95% credible interval -18·61 to -10·23]; 11 trials and 287 patients), cognitive therapy (-13·36 [-18·40 to -8·21]; six trials and 172 patients), behavioural therapy and clomipramine (-12·97 [-19·18 to -6·74]; one trial and 31 patients), cognitive behavioural therapy and fluvoxamine (-7·50 [-13·89 to -1·17]; one trial and six patients), cognitive behavioural therapy (-5·37 [-9·10 to -1·63]; nine trials and 231 patients), clomipramine (-4·72 [-6·85 to -2·60]; 13 trials and 831 patients), and all SSRIs (class effect -3·49 [95% credible interval -5·12 to -1·81]; 37 trials and 3158 patients) had greater effects than did drug placebo. Clomipramine was not better than were SSRIs (-1·23 [-3·41 to 0·94]). Psychotherapeutic interventions had a greater effect than did medications, but a serious limitation was that most psychotherapeutic trials included patients who were taking stable doses of antidepressants (12 [80%] of the 15 psychotherapy trials explicitly allowed antidepressants). Interpretation: A range of interventions is effective in the management of obsessive-compulsive disorder, but considerable uncertainty and limitations exist regarding their relative efficacy. Taking all the evidence into account, the combination of psychotherapeutic and psychopharmacological interventions is likely to be more effective than are psychotherapeutic interventions alone, at least in severe obsessive-compulsive disorder. Funding: National Institute for Health Research.

The lancet. Psychiatry · systematic review · 236 citationsread the source →

Trajectories of relapse in randomised, placebo-controlled trials of treatment discontinuation in major depressive disorder: an individual patient-level data meta-analysis.

Background: Understanding patterns of relapse in patients who respond to antidepressant treatment can inform strategies for prevention of relapse. We aimed to identify distinct trajectories of depression severity, assess whether similar or different trajectory classes exist for patients who continued or discontinued active treatment, and test whether clinical predictors of trajectory class membership exist using pooled data from clinical trials. Methods: We analysed individual patient data from four double-blind discontinuation clinical trials of duloxetine or fluoxetine versus placebo in major depression from before 2012 (n=1462). We modelled trajectories of relapse up to 26 weeks during double-blind treatment. Trajectories of depression severity, as measured by the Hamilton Depression Rating Scale score, were identified in the entire sample, and separately in groups in which antidepressants had been continued or discontinued, using growth mixture models. Predictors of trajectory class membership were assessed with weighted logistic regression. Findings: We identified similar relapse trajectories and two trajectories of stable depression scores in the normal range on active medication and on placebo. Active treatment significantly lowered the odds of membership in the relapse trajectory (odds ratio 0·47, 95% CI 0·37-0·61), whereas female sex (1·56, 1·23-2·06), shorter length of time with clinical response by 1 week (1·10, 1·06-1·15), and higher Clinical Global Impression score at baseline (1·28, 1·01-1·62) increased the odds. Overall, the protective effect of antidepressant medication relative to placebo on the risk of being classified as a relapser was about 13% (33% vs 46%). Interpretation: The existence of similar relapse trajectories on active medication and on placebo suggests that there is no specific relapse signature associated with antidepressant discontinuation. Furthermore, continued treatment offers only modest protection against relapse. These data highlight the need to incorporate treatment strategies that prevent relapse as part of the treatment of depression. Funding: National Institutes of Health, the US Department of Veterans Affairs Alcohol Research Center, and National Center for Post-Traumatic Stress Disorder.

The lancet. Psychiatry · randomised controlled trial · 49 citationsread the source →

The Healthy Activity Program (HAP), a lay counsellor-delivered brief psychological treatment for severe depression, in primary care in India: a randomised controlled trial.

Background: Although structured psychological treatments are recommended as first-line interventions for depression, only a small fraction of people globally receive these treatments because of poor access in routine primary care. We assessed the effectiveness and cost-effectiveness of a brief psychological treatment (Healthy Activity Program [HAP]) for delivery by lay counsellors to patients with moderately severe to severe depression in primary health-care settings. Methods: In this randomised controlled trial, we recruited participants aged 18-65 years scoring more than 14 on the Patient Health Questionnaire 9 (PHQ-9) indicating moderately severe to severe depression from ten primary health centres in Goa, India. Pregnant women or patients who needed urgent medical attention or were unable to communicate clearly were not eligible. Participants were randomly allocated (1:1) to enhanced usual care (EUC) alone or EUC combined with HAP in randomly sized blocks (block size four to six [two to four for men]), stratified by primary health centre and sex, and allocation was concealed with use of sequential numbered opaque envelopes. Physicians providing EUC were masked. Primary outcomes were depression symptom severity on the Beck Depression Inventory version II and remission from depression (PHQ-9 score of <10) at 3 months in the intention-to-treat population, assessed by masked field researchers. Secondary outcomes were disability, days unable to work, behavioural activation, suicidal thoughts or attempts, intimate partner violence, and resource use and costs of illness. We assessed serious adverse events in the per-protocol population. This trial is registered with the ISRCTN registry, number ISRCTN95149997. Findings: Between Oct 28, 2013, and July 29, 2015, we enrolled and randomly allocated 495 participants (247 [50%] to the EUC plus HAP group [two of whom were subsequently excluded because of protocol violations] and 248 [50%] to the EUC alone group), of whom 466 (95%) completed the 3 month primary outcome assessment (230 [49%] in the EUC plus HAP group and 236 [51%] in the EUC alone group). Participants in the EUC plus HAP group had significantly lower symptom severity (Beck Depression Inventory version II in EUC plus HAP group 19·99 [SD 15·70] vs 27·52 [13·26] in EUC alone group; adjusted mean difference -7·57 [95% CI -10·27 to -4·86]; p<0·0001) and higher remission (147 [64%] of 230 had a PHQ-9 score of <10 in the HAP plus EUC group vs 91 [39%] of 236 in the EUC alone group; adjusted prevalence ratio 1·61 [1·34-1·93]) than did those in the EUC alone group. EUC plus HAP showed better results than did EUC alone for the secondary outcomes of disability (adjusted mean difference -2·73 [-4·39 to -1·06]; p=0·001), days out of work (-2·29 [-3·84 to -0·73]; p=0·004), intimate partner physical violence in women (0·53 [0·29-0·96]; p=0·04), behavioural activation (2·17 [1·34-3·00]; p<0·0001), and suicidal thoughts or attempts (0·61 [0·45-0·83]; p=0·001). The incremental cost per quality-adjusted life-year gained was $9333 (95% CI 3862-28 169; 2015 international dollars), with an 87% chance of being cost-effective in the study setting. Serious adverse events were infrequent and similar between groups (nine [4%] in the EUC plus HAP group vs ten [4%] in the EUC alone group; p=1·00). Interpretation: HAP delivered by lay counsellors plus EUC was better than EUC alone was for patients with moderately severe to severe depression in routine primary care in Goa, India. HAP was readily accepted by this previously untreated population and was cost-effective in this setting. HAP could be a key strategy to reduce the treatment gap for depressive disorders, the leading mental health disorder worldwide. Funding: Wellcome Trust.

Lancet (London, England) · randomised controlled trial · 295 citationsread the source →

The SANTÉ study at 10 years of follow-up: Effectiveness, safety, and sudden unexpected death in epilepsy.

Objective: We evaluated the efficacy and safety of deep brain anterior thalamus stimulation after 7 and 10 years, and report the incidence of sudden unexpected death in epilepsy (SUDEP) and overall mortality in adults in the Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy (SANTÉ) study. Methods: After the 3-month blinded and 9-month unblinded phases, subjects continued to be assessed during long-term follow-up (LTFU) and later a continued therapy access phase (CAP), to further characterize adverse events and the incidence of SUDEP. Stimulus parameter and medication changes were allowed. Results: One hundred ten implanted subjects accumulated a total of 938 device-years of experience (69 subjects during the LTFU phase and 61 subjects in the CAP phase). Prior to study closure, 57 active subjects continued therapy at 14 study centers, with follow-up of at least 10 (maximum 14) years. At 7 years, median seizure frequency percent reduction from baseline was 75% (p < .001), with no outcome differences related to prior vagus nerve stimulation or resective surgery. The most severe seizure type, focal to bilateral tonic-clonic, was reduced by 71%. Adding new antiseizure medications did not impact the pattern of seizure reduction over time. There were no unanticipated serious adverse events in the study. The definite-plus-probable SUDEP rate, based on SANTÉ study experience (two deaths in 938 years) and previous pilot studies (0 deaths in 76 years), indicated a rate of 2.0 deaths for 1000 person-years. Overall mortality was 6.9 deaths per 1000 person-years. Significance: The long-term efficacy and safety profiles of the deep brain stimulation (DBS) system for epilepsy are favorable and demonstrate stable outcomes. Improvement in frequency of the most severe seizure type may reduce SUDEP risk. The SUDEP rate with DBS (2.0) is comparable to other neuromodulation treatments (i.e., vagus nerve stimulation, responsive neurostimulation) for drug-resistant focal epilepsy.

Epilepsia · randomised controlled trial · 251 citationsread the source →

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

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

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

Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial.

Background: The antiviral efficacy of remdesivir against SARS-CoV-2 is still controversial. We aimed to evaluate the clinical efficacy of remdesivir plus standard of care compared with standard of care alone in patients admitted to hospital with COVID-19, with indication of oxygen or ventilator support. Methods: DisCoVeRy was a phase 3, open-label, adaptive, multicentre, randomised, controlled trial conducted in 48 sites in Europe (France, Belgium, Austria, Portugal, Luxembourg). Adult patients (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and illness of any duration were eligible if they had clinical evidence of hypoxaemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzymes, severe chronic kidney disease, any contraindication to one of the studied treatments or their use in the 29 days before random assignment, or use of ribavirin, as well as pregnancy or breastfeeding. Participants were randomly assigned (1:1:1:1:1) to receive standard of care alone or in combination with remdesivir, lopinavir-ritonavir, lopinavir-ritonavir and interferon beta-1a, or hydroxychloroquine. Randomisation used computer-generated blocks of various sizes; it was stratified on severity of disease at inclusion and on European administrative region. Remdesivir was administered as 200 mg intravenous infusion on day 1, followed by once daily, 1-h infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. The primary outcome was the clinical status at day 15 measured by the WHO seven-point ordinal scale, assessed in the intention-to-treat population. Safety was assessed in the modified intention-to-treat population and was one of the secondary outcomes. This trial is registered with the European Clinical Trials Database, EudraCT2020-000936-23, and ClinicalTrials.gov, NCT04315948. Findings: Between March 22, 2020, and Jan 21, 2021, 857 participants were enrolled and randomly assigned to remdesivir plus standard of care (n=429) or standard of care only (n=428). 15 participants were excluded from analysis in the remdesivir group, and ten in the control group. At day 15, the distribution of the WHO ordinal scale was: (1) not hospitalised, no limitations on activities (61 [15%] of 414 in the remdesivir group vs 73 [17%] of 418 in the control group); (2) not hospitalised, limitation on activities (129 [31%] vs 132 [32%]); (3) hospitalised, not requiring supplemental oxygen (50 [12%] vs 29 [7%]); (4) hospitalised, requiring supplemental oxygen (76 [18%] vs 67 [16%]); (5) hospitalised, on non-invasive ventilation or high flow oxygen devices (15 [4%] vs 14 [3%]); (6) hospitalised, on invasive mechanical ventilation or extracorporeal membrane oxygenation (62 [15%] vs 79 [19%]); (7) death (21 [5%] vs 24 [6%]). The difference between treatment groups was not significant (odds ratio 0·98 [95% CI 0·77-1·25]; p=0·85). There was no significant difference in the occurrence of serious adverse events between treatment groups (remdesivir, 135 [33%] of 406 vs control, 130 [31%] of 418; p=0·48). Three deaths (acute respiratory distress syndrome, bacterial infection, and hepatorenal syndrome) were considered related to remdesivir by the investigators, but only one by the sponsor's safety team (hepatorenal syndrome). Interpretation: No clinical benefit was observed from the use of remdesivir in patients who were admitted to hospital for COVID-19, were symptomatic for more than 7 days, and required oxygen support. Funding: European Union Commission, French Ministry of Health, Domaine d'intérêt majeur One Health Île-de-France, REACTing, Fonds Erasme-COVID-Université Libre de Bruxelles, Belgian Health Care Knowledge Centre, Austrian Group Medical Tumor, European Regional Development Fund, Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation. Translation: For the French translation of the abstract see Supplementary Materials section.

The Lancet. Infectious diseases · randomised controlled trial · 264 citationsread the source →

Randomised clinical non-inferiority trial of breathing-based meditation and cognitive processing therapy for symptoms of post-traumatic stress disorder in military veterans.

Objective: Test whether Sudarshan Kriya Yoga (SKY) was non-inferior to cognitive processing therapy (CPT) for treating symptoms of post-traumatic stress disorder (PTSD) among veterans via a parallel randomised controlled non-inferiority trial. Setting: Outpatient Veterans Affairs healthcare centre. Participants: 85 veterans (75 men, 61% white, mean age 56.9) with symptoms of PTSD participated between October 2015 and March 2020: 59 participants completed the study. Interventions: SKY emphasises breathing routines and was delivered in group format in a 15-hour workshop followed by two 1-hour sessions per week for 5 weeks. CPT is an individual psychotherapy which emphasises shifting cognitive appraisals and was delivered in two 1-hour sessions per week for 6 weeks. Measures: The primary outcome measure was the PTSD Checklist-Civilian Version (PCL-C). The secondary measures were the Beck Depression Inventory-II (BDI-II) and Positive and Negative Affect Scale (PANAS). Results: Mean PCL-C at baseline was 56.5 (±12.6). Intent-to-treat analyses showed that PCL-C scores were reduced at 6 weeks (end of treatment) relative to baseline (SKY, -5.6, d=0.41, n=41: CPT, -6.8, d=0.58, n=44). The between-treatment difference in change scores was within the non-inferiority margin of 10 points (-1.2, 95% CI -5.7 to 3.3), suggesting SKY was not inferior to CPT. SKY was also non-inferior at 1-month (CPT-SKY: -2.1, 95% CI -6.9 to 2.8) and 1-year (CPT-SKY: -1.8, 95% CI -6.6 to 2.9) assessments. SKY was also non-inferior to CPT on the BDI-II and PANAS at end of treatment and 1 month, but SKY was inferior to CPT on both BDI-II and PANAS at 1 year. Dropout rates were similar (SKY, 27%, CPT, 34%: OR=1.36, 95% CI 0.51 to 3.62, p=0.54). Conclusions: SKY may be non-inferior to CPT for treating symptoms of PTSD and merits further consideration as a treatment for PTSD. Trial registration number: NCT02366403.

BMJ open · randomised controlled trial · 15 citationsread the source →

Computerized Cognitive Training for Amelioration of Cognitive Late Effects Among Childhood Cancer Survivors: A Randomized Controlled Trial.

Purpose: Children receiving CNS-directed therapy for cancer are at risk for cognitive problems, with few available empirically supported interventions. Cognitive problems indicate neurodevelopmental disruption that may be modifiable with intervention. This study evaluated short-term efficacy of a computerized cognitive training program and neural correlates of cognitive change. Patient and methods: A total of 68 survivors of childhood acute lymphoblastic leukemia (ALL) or brain tumor (BT) with identified cognitive deficits were randomly assigned to computerized cognitive intervention (male, n = 18; female, n = 16; ALL, n = 23; BT, n = 11; mean age ± standard deviation, 12.21 ± 2.47 years) or waitlist (male, n = 18; female, n = 16; ALL, n = 24; BT, n = 10; median age ± standard deviation, 11.82 ± 2.42 years). Intervention participants were asked to complete 25 training sessions at home with weekly, telephone-based coaching. Cognitive assessments and functional magnetic resonance imaging scans (intervention group) were completed pre- and postintervention, with immediate change in spatial span backward as the primary outcome. Results: Survivors completing the intervention (n = 30; 88%) demonstrated greater improvement than controls on measures of working memory (mean ± SEM; eg, Wechsler Intelligence Scale for Children [fourth edition; WISC-IV] spatial span backward, 3.13 ± 0.58 v 0.75 ± 0.43; P = .002; effect size [ES], 0.84), attention (eg, WISC-IV spatial span forward, 3.30 ± 0.71 v 1.25 ± 0.39; P = .01; ES, 0.65), and processing speed (eg, Conners' Continuous Performance Test hit reaction time, -2.10 ± 1.47 v 2.54 ± 1.25; P = .02; ES, .61) and showed greater reductions in reported executive dysfunction (eg, Conners' Parent Rating Scale III, -6.73 ± 1.51 v 0.41 ± 1.53; P = .002; ES, 0.84). Functional magnetic resonance imaging revealed significant pre- to post-training reduction in activation of left lateral prefrontal and bilateral medial frontal areas. Conclusion: Study findings show computerized cognitive training is feasible and efficacious for childhood cancer survivors, with evidence for training-related neuroplasticity.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology · randomised controlled trial · 119 citationsread the source →

Impact of a combined multimodal-aerobic and multimodal intervention compared to standard aerobic treatment in breast cancer survivors with chronic cancer-related fatigue - results of a three-armed pragmatic trial in a comprehensive cohort design.

Background: Cancer-related fatigue (CRF) and insomnia are major complaints in breast cancer survivors (BC). Aerobic training (AT), the standard therapy for CRF in BC, shows only minor to moderate treatment effects. Other evidence-based treatments include cognitive behavioral therapy, e.g., sleep education/restriction (SE) and mindfulness-based therapies. We investigated the effectiveness of a 10-week multimodal program (MT) consisting of SE, psycho-education, eurythmy- and painting-therapy, administered separately or in combination with AT (CT) and compared both arms to AT alone. Methods: In a pragmatic comprehensive cohort study BC with chronic CRF were allocated randomly or by patient preference to (a) MT, (b) CT (MT + AT) or (c) AT alone. Primary endpoint was a composite score of the Pittsburgh Sleep Quality Index and the Cancer Fatigue Scale after 10 weeks of intervention (T1); a second endpoint was a follow-up assessment 6 months later (T2). The primary hypothesis stated superiority of CT and non-inferiority of MT vs. AT at T1. A closed testing procedure preserved the global α-level. The intention-to-treat analysis included propensity scores for the mode of allocation and for the preferred treatment, respectively. Results: Altogether 126 BC were recruited: 65 were randomized and 61 allocated by preference; 105 started the intervention. Socio-demographic parameters were generally balanced at baseline. Non-inferiority of MT to AT at T1 was confirmed (p < 0.05), yet the confirmative analysis stopped as it was not possible to confirm superiority of CT vs. AT (p = 0.119). In consecutive exploratory analyses MT and CT were superior to AT at T1 and T2 (MT) or T2 alone (CT), respectively. Conclusions: The multimodal CRF-therapy was found to be confirmatively non-inferior to standard therapy and even yielded exploratively sustained superiority. A randomized controlled trial including a larger sample size and a longer follow-up to evaluate multimodal CRF-therapy is highly warranted. Trial register: DRKS-ID: DRKS00003736 . Recruitment period June 2011 to March 2013. Date of registering 19 June 2012.

BMC cancer · randomised controlled trial · 41 citationsread the source →

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

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

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

Towards universal voluntary HIV testing and counselling: a systematic review and meta-analysis of community-based approaches.

Background: Effective national and global HIV responses require a significant expansion of HIV testing and counselling (HTC) to expand access to prevention and care. Facility-based HTC, while essential, is unlikely to meet national and global targets on its own. This article systematically reviews the evidence for community-based HTC. Methods and findings: PubMed was searched on 4 March 2013, clinical trial registries were searched on 3 September 2012, and Embase and the World Health Organization Global Index Medicus were searched on 10 April 2012 for studies including community-based HTC (i.e., HTC outside of health facilities). Randomised controlled trials, and observational studies were eligible if they included a community-based testing approach and reported one or more of the following outcomes: uptake, proportion receiving their first HIV test, CD4 value at diagnosis, linkage to care, HIV positivity rate, HTC coverage, HIV incidence, or cost per person tested (outcomes are defined fully in the text). The following community-based HTC approaches were reviewed: (1) door-to-door testing (systematically offering HTC to homes in a catchment area), (2) mobile testing for the general population (offering HTC via a mobile HTC service), (3) index testing (offering HTC to household members of people with HIV and persons who may have been exposed to HIV), (4) mobile testing for men who have sex with men, (5) mobile testing for people who inject drugs, (6) mobile testing for female sex workers, (7) mobile testing for adolescents, (8) self-testing, (9) workplace HTC, (10) church-based HTC, and (11) school-based HTC. The Newcastle-Ottawa Quality Assessment Scale and the Cochrane Collaboration's "risk of bias" tool were used to assess the risk of bias in studies with a comparator arm included in pooled estimates. 117 studies, including 864,651 participants completing HTC, met the inclusion criteria. The percentage of people offered community-based HTC who accepted HTC was as follows: index testing, 88% of 12,052 participants; self-testing, 87% of 1,839 participants; mobile testing, 87% of 79,475 participants; door-to-door testing, 80% of 555,267 participants; workplace testing, 67% of 62,406 participants; and school-based testing, 62% of 2,593 participants. Mobile HTC uptake among key populations (men who have sex with men, people who inject drugs, female sex workers, and adolescents) ranged from 9% to 100% (among 41,110 participants across studies), with heterogeneity related to how testing was offered. Community-based approaches increased HTC uptake (relative risk [RR] 10.65, 95% confidence interval [CI] 6.27-18.08), the proportion of first-time testers (RR 1.23, 95% CI 1.06-1.42), and the proportion of participants with CD4 counts above 350 cells/µl (RR 1.42, 95% CI 1.16-1.74), and obtained a lower positivity rate (RR 0.59, 95% CI 0.37-0.96), relative to facility-based approaches. 80% (95% CI 75%-85%) of 5,832 community-based HTC participants obtained a CD4 measurement following HIV diagnosis, and 73% (95% CI 61%-85%) of 527 community-based HTC participants initiated antiretroviral therapy following a CD4 measurement indicating eligibility. The data on linking participants without HIV to prevention services were limited. In low- and middle-income countries, the cost per person tested ranged from US$2-US$126. At the population level, community-based HTC increased HTC coverage (RR 7.07, 95% CI 3.52-14.22) and reduced HIV incidence (RR 0.86, 95% CI 0.73-1.02), although the incidence reduction lacked statistical significance. No studies reported any harm arising as a result of having been tested. Conclusions: Community-based HTC achieved high rates of HTC uptake, reached people with high CD4 counts, and linked people to care. It also obtained a lower HIV positivity rate relative to facility-based approaches. Further research is needed to further improve acceptability of community-based HTC for key populations. HIV programmes should offer community-based HTC linked to prevention and care, in addition to facility-based HTC, to support increased access to HIV prevention, care, and treatment. Review registration: International Prospective Register of Systematic Reviews CRD42012002554 Please see later in the article for the Editors' Summary.

PLoS medicine · meta-analysis · 313 citationsread the source →

Enduring mental health morbidity and social function impairment in world trade center rescue, recovery, and cleanup workers: the psychological dimension of an environmental health disaster.

Background: The World Trade Center (WTC) attacks exposed thousands of workers to hazardous environmental conditions and psychological trauma. In 2002, to assess the health of these workers, Congress directed the National Institute for Occupational Safety and Health to establish the WTC Medical Monitoring and Treatment Program. This program has established a large cohort of WTC rescue, recovery, and cleanup workers. We previously documented extensive pulmonary dysfunction in this cohort related to toxic environmental exposures. Objectives: Our objective in this study was to describe mental health outcomes, social function impairment, and psychiatric comorbidity in the WTC worker cohort, as well as perceived symptomatology in workers' children. Methods: Ten to 61 months after the WTC attack, 10,132 WTC workers completed a self-administered mental health questionnaire. Results: Of the workers who completd the questionnaire, 11.1% met criteria for probable post-traumatic stress disorder (PTSD), 8.8% met criteria for probable depression, 5.0% met criteria for probable panic disorder, and 62% met criteria for substantial stress reaction. PTSD prevalence was comparable to that seen in returning Afghanistan war veterans and was much higher than in the U.S. general population. Point prevalence declined from 13.5% to 9.7% over the 5 years of observation. Comorbidity was extensive and included extremely high risks for impairment of social function. PTSD was significantly associated with loss of family members and friends, disruption of family, work, and social life, and higher rates of behavioral symptoms in children of workers. Conclusions: Working in 9/11 recovery operations is associated with chronic impairment of mental health and social functioning. Psychological distress and psychopathology in WTC workers greatly exceed population norms. Surveillance and treatment programs continue to be needed.

Environmental health perspectives · 129 citationsread the source →

Effect of immunotherapy time-of-day infusion on overall survival among patients with advanced melanoma in the USA (MEMOIR): a propensity score-matched analysis of a single-centre, longitudinal study.

Background: The dependence of the adaptive immune system on circadian rhythm is an emerging field of study with potential therapeutic implications. We aimed to determine whether specific time-of-day patterns of immune checkpoint inhibitor infusions might alter melanoma treatment efficacy. Methods: Melanoma Outcomes Following Immunotherapy (MEMOIR) is a longitudinal study of all patients with melanoma who received ipilimumab, nivolumab, or pembrolizumab, or a combination of these at a single tertiary cancer centre (Winship Cancer Institute of Emory University, Atlanta, GA, USA). For this analysis, we collected deidentified participant-level data from the MEMOIR database for adults (age ≥18 years) diagnosed with stage IV melanoma between 2012 and 2020. Those who received fewer than four infusions were excluded. Standard of care doses were used, with modifications at the treating physicians' discretion. The primary outcome was overall survival, defined as death from any cause and indexed from date of first infusion of immune checkpoint inhibitor. We calculated the association between overall survival and proportion of infusions of immune checkpoint inhibitors received after 1630 h (a composite time cutoff derived from seminal studies of the immune-circadian rhythm to represent onset of evening) using Cox regression and propensity score-matching on age, Eastern Cooperative Oncology Group performance status, serum lactate dehydrogenase concentration, and receipt of corticosteroids and radiotherapy. Treatment-related adverse events that led to change or discontinuation of immune checkpoint inhibitors were also assessed. Findings: Between Jan 1, 2012, and Dec 31, 2020, 481 patients with melanoma received treatment with immune checkpoint inhibitors at the study centre, of whom 299 had stage IV disease and were included in this study; median follow-up was 27 months (IQR 14 to 47). In the complete unmatched sample, 102 (34%) patients were female and 197 (66%) were male, with a median age of 61 years (IQR 51 to 72). Every additional 20% of infusions of immune checkpoint inhibitors received after 1630 h (among all infusions received by a patient) conferred an overall survival hazard ratio (HR) of 1·31 (95% CI 1·00 to 1·71; p=0·046). A propensity score-matched analysis of patients who did (n=73) and did not (n=73) receive at least 20% of their infusions of immune checkpoint inhibitors after 1630 h (54 [37%] of 146 patients were women and 92 [63%] were men, with a median age of 58 years [IQR 48 to 68]) showed that having at least 20% of infusions in the evening was associated with shorter overall survival (median 4·8 years [95% CI 3·9 to not estimable] vs not reached; HR 2·04 [1·04 to 4·00; p=0·038]). This result remained robust to multivariable proportional hazards adjustment with (HR 1·80 [1·08 to 2·98; p=0·023]) and without (2·16 [1·10 to 4·25; p=0·025]) inclusion of the complete unmatched study sample. The most common adverse events were colitis (54 [18%] of 299 patients), hepatitis (27 [9%]), and hypophysitis (15 [5%]), and there were no treatment-related deaths. Interpretation: Our findings are in line with an increasing body of evidence that adaptive immune responses are less robust when initially stimulated in the evening than if stimulated in the daytime. Although prospective studies of the timing of immune checkpoint inhibitor infusions are warranted, efforts towards scheduling infusions before mid-afternoon could be considered in the multidisciplinary management of advanced melanoma. Funding: National Institutes of Health, American Society for Radiation Oncology and Melanoma Research Alliance, and Winship Cancer Institute.

The Lancet. Oncology · clinical trial · 146 citationsread the source →

Replication of ketamine's antidepressant efficacy in bipolar depression: a randomized controlled add-on trial.

Background: Currently, no pharmacological treatments for bipolar depression exist that exert rapid (within hours) antidepressant or antisuicidal effects. We previously reported that intravenous administration of the N-methyl-D-aspartate antagonist ketamine produced rapid antidepressant effects in patients with treatment-resistant bipolar depression. The present study sought to replicate this finding in an independent sample. Methods: In this double-blind, randomized, crossover, placebo-controlled study, 15 subjects with DSM-IV bipolar I or II depression maintained on therapeutic levels of lithium or valproate received a single intravenous infusion of either ketamine hydrochloride (.5 mg/kg) or placebo on 2 test days 2 weeks apart. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale, which was used to rate overall depressive symptoms at baseline; at 40, 80, 110, and 230 minutes postinfusion; and on days 1, 2, 3, 7, 10, and 14 postinfusion. Results: Within 40 minutes, depressive symptoms, as well as suicidal ideation, significantly improved in subjects receiving ketamine compared with placebo (d = .89, 95% confidence interval = .61-1.16, and .98, 95% confidence interval = .64-1.33, respectively); this improvement remained significant through day 3. Seventy-nine percent of subjects responded to ketamine and 0% responded to placebo at some point during the trial. The most common side effect was dissociative symptoms, which occurred only at the 40-minute time point. Conclusions: This study replicated our previous finding that patients with bipolar depression who received a single ketamine infusion experienced a rapid and robust antidepressant response. In addition, we found that ketamine rapidly improved suicidal ideation in these patients.

Biological psychiatry · randomised controlled trial · 586 citationsread the source →

Internet-based intervention for smoking cessation (StopAdvisor) in people with low and high socioeconomic status: a randomised controlled trial.

Background: Internet-based interventions for smoking cessation could help millions of people stop smoking at very low unit costs; however, long-term biochemically verified evidence is scarce and such interventions might be less effective for smokers with low socioeconomic status than for those with high status because of lower online literacy to engage with websites. We aimed to assess a new interactive internet-based intervention (StopAdvisor) for smoking cessation that was designed with particular attention directed to people with low socioeconomic status. Methods: We did this online randomised controlled trial between Dec 6, 2011, and Oct 11, 2013, in the UK. Participants aged 18 years and older who smoked every day were randomly assigned (1:1) to receive treatment with StopAdvisor or an information-only website. Randomisation was automated with an unseen random number function embedded in the website to establish which treatment was revealed after the online baseline assessment. Recruitment continued until the required sample size had been achieved from both high and low socioeconomic status subpopulations. Participants, and researchers who obtained data and did laboratory analyses, were masked to treatment allocation. The primary outcome was 6 month sustained, biochemically verified abstinence. The main secondary outcome was 6 month, 7 day biochemically verified point prevalence. Analysis was by intention to treat. Homogeneity of intervention effect across the socioeconomic subsamples was first assessed to establish whether overall or separate subsample analyses were appropriate. The study is registered as an International Standard Randomised Controlled Trial, number ISRCTN99820519. Findings: We randomly assigned 4613 participants to the StopAdvisor group (n=2321) or the control group (n=2292); 2142 participants were of low socioeconomic status and 2471 participants were of high status. The overall rate of smoking cessation was similar between participants in the StopAdvisor and control groups for the primary (237 [10%] vs 220 [10%] participants; relative risk [RR] 1·06, 95% CI 0·89-1·27; p=0·49) and the secondary (358 [15%] vs 332 [15%] participants; 1·06, 0·93-1·22; p=0·37) outcomes; however, the intervention effect differed across socioeconomic status subsamples (1·44, 0·99-2·09; p=0·0562 and 1·37, 1·02-1·84; p=0·0360, respectively). StopAdvisor helped participants with low socioeconomic status stop smoking compared with the information-only website (primary outcome: 90 [8%] of 1088 vs 64 [6%] of 1054 participants; RR 1·36, 95% CI 1·00-1·86; p=0·0499; secondary outcome: 136 [13%] vs 100 [10%] participants; 1·32, 1·03-1·68, p=0·0267), but did not improve cessation rates in those with high socioeconomic status (147 [12%] of 1233 vs 156 [13%] of 1238 participants; 0·95, 0·77-1·17; p=0·61 and 222 [18%] vs 232 [19%] participants; 0·96, 0·81-1·13, p=0·64, respectively). Interpretation: StopAdvisor was more effective than an information-only website in smokers of low, but not high, socioeconomic status. StopAdvisor could be implemented easily and made freely available, which would probably improve the success rates of smokers with low socioeconomic status who are seeking online support. Funding: National Prevention Research Initiative.

The Lancet. Respiratory medicine · randomised controlled trial · 99 citationsread the source →

Effectiveness of a school-based group psychotherapy program for war-exposed adolescents: a randomized controlled trial.

Objective: To evaluate the comparative effectiveness of a classroom-based psychoeducation and skills intervention (tier 1) and a school-based trauma- and grief-focused group treatment (tier 2) of a three-tiered mental health program for adolescents exposed to severe war-related trauma, traumatic bereavement, and postwar adversity. Method: A total of 127 war-exposed and predominantly ethnic Muslim secondary school students attending 10 schools in central Bosnia who reported severe symptoms of posttraumatic stress disorder (PTSD), depression, or maladaptive grief and significant impairment in school or relationships were randomly assigned to one of two experimental conditions. These included either an active-treatment comparison condition (tier 1), consisting of a classroom-based psychoeducation and skills intervention alone (n = 61, 66% girls, mean age 16.0 years, SD 1.13) or a treatment condition composed of both the classroom-based intervention and a 17-session manual-based group therapy intervention (tier 2), trauma and grief component therapy for adolescents (n = 66, 63% girls, mean age 15.9 years, SD 1.11). Both interventions were implemented throughout the school year. Distressed students who were excluded from the study due to acute risk for harm (n = 9) were referred for community-based mental health services (tier 3). Results: Program effectiveness was measured via reductions in symptoms of PTSD, depression, and maladaptive grief assessed at pretreatment, posttreatment, and 4-month follow-up. Analysis of mean-level treatment effects showed significant pre- to posttreatment and posttreatment to 4-month follow-up reductions in PTSD and depression symptoms in both the treatment and comparison conditions. Significant pre- to posttreatment reductions in maladaptive grief reactions were found only in the treatment condition. Analyzed at the individual case level, the percentages of students in the treatment condition who reported significant (p <.05) pre- to posttreatment reductions in PTSD symptoms (58% at posttreatment, 81% at 4-month follow-up) compare favorably to those reported in controlled treatment efficacy trials, whereas the percentages who reported significant reductions in depression symptoms (23% at posttreatment, 61% at follow-up) are comparable to, or higher than, those found in community treatment settings. Lower but substantial percentages of significant symptom reduction were found for PTSD (33% at posttreatment, 48% at follow-up) and depression symptoms (13% at posttreatment; 47% at follow-up) in students in the comparison condition. The odds of significant symptom reduction were higher for PTSD symptoms at both posttreatment and 4-month follow-up and for maladaptive grief at posttreatment (no follow-up was conducted on maladaptive grief). Rates of significantly worsened cases were generally rare in both the treatment and comparison conditions. Conclusions: A three-tiered, integrative mental health program composed of schoolwide dissemination of psychoeducation and coping skills (tier 1), specialized trauma- and grief-focused intervention for severely traumatized and traumatically bereaved youths (tier 2), and referral of youths at acute risk for community-based mental health services (tier 3) constitutes an effective and efficient method for promoting adolescent recovery in postwar settings.

Journal of the American Academy of Child and Adolescent Psychiatry · randomised controlled trial · 141 citationsread the source →

Reducing sedentary behaviour and increasing physical activity among 10-year-old children: overview and process evaluation of the 'Switch-Play' intervention.

Overweight and obesity has doubled among children in Australia. There is an urgent need to develop primary prevention strategies to prevent current and future unhealthy weight gain. The aims of this paper are to describe a randomized controlled trial ('Switch-Play') developed to prevent unhealthy weight gain among 10-year-old children and to report the findings of the process evaluation. Children from three government primary schools were randomized by class to one of four conditions: a behavioural modification group (BM; n = 69); a fundamental motor skills group (FMS; n = 73); a combined BM and FMS group (n = 90); or a control (usual classroom lessons) group (n = 61). Children in the BM group participated in 19 sessions that encouraged them to reduce screen-based behaviours, and identified physical activity alternatives. The FMS group participated in 19 lessons that focused on mastery of six skills: run, throw, dodge, strike, vertical jump and kick. The combined group participated in all the BM and FMS activities. The intervention specialist teacher reported that the children showed high enjoyment and engagement (88% lessons attended) in most aspects of the programme. At-home tasks were completed by 57-62% of the children, and 92% completed the in-class tasks. Two-thirds of the children in the BM group participated in the behavioural contracting to switch off the TV. Most of the children reported high enjoyment of the programmes, and only a small proportion (7-17%) reported difficulties in switching off their nominated TV shows. More than half the children reported reducing their TV viewing; however, less than half reported increasing their physical activity. It was found that most aspects of the intervention arms of the programme were successfully delivered to the majority of children participating in 'Switch-Play'; that the programmes were delivered as intended; and that the programmes were favourably evaluated by participating children and their parents.

Health promotion international · randomised controlled trial · 30 citationsread the source →

The effect of telithromycin in acute exacerbations of asthma.

Background: We conducted a double-blind, randomized, placebo-controlled study to evaluate the efficacy of telithromycin in patients with acute exacerbations of asthma. Methods: A total of 278 adults with diagnosed asthma were enrolled within 24 hours after an acute exacerbation of asthma requiring short-term medical care. The patients were randomly assigned to receive 10 days of oral treatment with telithromycin (at a dose of 800 mg daily) or placebo in addition to usual care. Primary efficacy end points were a change from baseline over the treatment period in symptoms (as recorded by patients in a diary card) and in the peak expiratory flow in the morning at home. The presence of Chlamydophila pneumoniae or Mycoplasma pneumoniae was ascertained by serologic analysis, polymerase chain reaction, and culture. Results: Of the two prespecified primary outcomes, only asthma symptoms showed a significantly greater reduction among patients receiving telithromycin than among those receiving placebo. Mean (+/-SD) scores on a test of asthma symptoms (on a 7-point scale, with 0 denoting no symptoms and 6 denoting severe symptoms) were 3.0+/-1.4 at baseline and 1.7+/-1.1 at the end of treatment for the telithromycin group and 2.8+/-1.3 at baseline and 2.0+/-1.0 at the end of treatment for the placebo group. The mean decrease in symptom scores during the treatment period was 1.3 for telithromycin and 1.0 for placebo (mean difference, -0.3; 95 percent confidence interval, -0.5 to -0.1; P=0.004). There was no significant treatment effect on the other primary outcome measure, a change in morning peak expiratory flow. Nausea was more common among patients in the telithromycin group than in the placebo group (P=0.01). Although 61 percent of patients had evidence of infection with C. pneumoniae, M. pneumoniae, or both, there was no relationship between bacteriologic status and the response to asthma treatment. Conclusions: This study provides evidence of the benefit of telithromycin in patients with acute exacerbations of asthma; the mechanisms of benefit remain unclear. (ClinicalTrials.gov number, NCT00273520.).

The New England journal of medicine · randomised controlled trial · 184 citationsread the source →

Long-term quality-of-life outcomes after radical prostatectomy or watchful waiting: the Scandinavian Prostate Cancer Group-4 randomised trial.

Background: For men with localised prostate cancer, surgery provides a survival benefit compared with watchful waiting. Treatments are associated with morbidity. Results for functional outcome and quality of life are rarely reported beyond 10 years and are lacking from randomised settings. We report results for quality of life for men in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) after a median follow-up of more than 12 years. Methods: All living Swedish and Finnish men (400 of 695) randomly assigned to radical prostatectomy or watchful waiting in SPCG-4 from 1989 to 1999 were included in our analysis. An additional 281 men were included in a population-based control group matched for region and age. Physical symptoms, symptom-induced stress, and self-assessed quality of life were evaluated with a study-specific questionnaire. Longitudinal data were available for 166 Swedish men who had answered quality-of-life questionnaires at an earlier timepoint. Findings: 182 (88%) of 208 men in the radical prostatectomy group, 167 (87%) of 192 men in the watchful-waiting group, and 214 (76%) of 281 men in the population-based control group answered the questionnaire. Men in SPCG-4 had a median follow-up of 12·2 years (range 7-17) and a median age of 77·0 years (range 61-88). High self-assessed quality of life was reported by 62 (35%) of 179 men allocated radical prostatectomy, 55 (34%) of 160 men assigned to watchful waiting, and 93 (45%) of 208 men in the control group. Anxiety was higher in the SPCG-4 groups (77 [43%] of 178 and 69 [43%] of 161 men) than in the control group (68 [33%] of 208 men; relative risk 1·42, 95% CI 1·07-1·88). Prevalence of erectile dysfunction was 84% (146 of 173 men) in the radical prostatectomy group, 80% (122 of 153) in the watchful-waiting group, and 46% (95 of 208) in the control group and prevalence of urinary leakage was 41% (71 of 173), 11% (18 of 164), and 3% (six of 209), respectively. Distress caused by these symptoms was reported significantly more often by men allocated radical prostatectomy than by men assigned to watchful waiting. In a longitudinal analysis of men in SPCG-4 who provided information at two follow-up points 9 years apart, 38 (45%) of 85 men allocated radical prostatectomy and 48 (60%) of 80 men allocated watchful waiting reported an increase in number of physical symptoms; 50 (61%) of 82 and 47 (64%) of 74 men, respectively, reported a reduction in quality of life. Interpretation: For men in SPCG-4, negative side-effects were common and added more stress than was reported in the control population. In the radical prostatectomy group, erectile dysfunction and urinary leakage were often consequences of surgery. In the watchful-waiting group, side-effects can be caused by tumour progression. The number and severity of side-effects changes over time at a higher rate than is caused by normal ageing and a loss of sexual ability is a persistent psychological problem for both interventions. An understanding of the patterns of side-effects and time dimension of their occurrence for each treatment is important for full patient information. Funding: US National Institutes of Health; Swedish Cancer Society; Foundation in Memory of Johanna Hagstrand and Sigfrid Linnér.

The Lancet. Oncology · randomised controlled trial · 277 citationsread the source →

The influence of medical and psychological interventions on women's distress after miscarriage.

Objective: The aim of this study was to examine the impact of medical and psychological interventions on women's distress after early miscarriage. Methods: This was a prospective study of women attending for a routine scan at 10-14 weeks of gestation and found to have a missed miscarriage. An intervention group of 66 women had medical investigations to ascertain the cause of miscarriage, and at 5 weeks after the scan, they all had a medical consultation to discuss the results of the investigations. These 66 women were randomly allocated into a group which received further psychological counselling (MPC, n=33), and a group which received no psychological counselling (MC, n=33). They were compared to a control group of 61 women who received no specific postmiscarriage counselling. All participants completed preintervention and postintervention measures and 4-month follow-up questionnaires. Results: The scores on the outcome variables decreased significantly with time for all three groups. In group MPC, compared to controls, there was a significantly greater decrease over time in the levels of grief, self-blame, and worry and, compared to MC group, a significantly greater decrease in grief and worry. In group MC, compared to controls, there was a significantly greater decrease in self-blame. In the MC and MPC groups, those with an identified cause of the miscarriage had significantly lower levels of anxiety and self-blame over time than those with a nonidentified cause. Conclusions: Psychological counselling, in addition to medical investigations and consultation, is beneficial in reducing women's distress after miscarriage. However, absence of an identifiable cause of miscarriage led to the maintenance of the initial anxiety levels, which should have otherwise decreased with time.

Journal of psychosomatic research · randomised controlled trial · 58 citationsread the source →

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

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

JAMA · randomised controlled trial · 181 citationsread the source →

Breaking bad news: what parents would like you to know.

Objective: Breaking bad news about life-threatening and possibly terminal conditions is a crucial part of paediatric care for children in this situation. Little is known about how the parents of children with life-threatening conditions experience communication of bad news. The objective of this study is to analyse parents' experiences (barriers and facilitators) of communication of bad news. Design: A qualitative study consisting of a constant comparative analysis of in-depth interviews conducted with parents. Setting: The Netherlands. Participants: Sixty-four parents-bereaved and non-bereaved-of 44 children (aged 1-12 years, 61% deceased) with a life-threatening condition. Interventions: None. Results: Based on parents' experiences, the following 10 barriers to the communication of bad news were identified: (1) a lack of (timely) communication, (2) physicians' failure to ask parents for input, (3) parents feel unprepared during and after the conversation, (4) a lack of clarity about future treatment, (5) physicians' failure to voice uncertainties, (6) physicians' failure to schedule follow-up conversations, (7) presence of too many or unknown healthcare professionals, (8) parental concerns in breaking bad news to children, (9) managing indications of bad news in non-conversational contexts, and (10) parents' misunderstanding of medical terminology. Conclusions: This study shows healthcare professionals how parents experience barriers in bad news conversations. This mainly concerns practical aspects of communication. The results provide practical pointers on how the communication of bad news can be improved to better suit the needs of parents. From the parents' perspective, the timing of conversations in which they were informed that their child might not survive was far too late. Sometimes, no such conversations ever took place.

Archives of disease in childhood · cohort or longitudinal · 49 citationsread the source →

Methylphenidate and the risk of psychosis in adolescents and young adults: a population-based cohort study.

Background: There is a clinical concern that prescribing methylphenidate, the most common pharmacological treatment for attention-deficit hyperactivity disorder (ADHD), might increase the risk of psychotic events, particularly in young people with a history of psychosis. We aimed to determine whether the risk of psychotic events increases immediately after initiation of methylphenidate treatment or, in the longer term, 1 year after treatment initiation in adolescents and young adults with and without a previously diagnosed psychotic disorder. Methods: In this cohort study, we used population-based observational data from the Swedish Prescribed Drug Register, the National Patient Register, and the Total Population Register, three population-based registers containing data on all individuals in Sweden, to attain data on sex, birth, death, migration, medication use, and psychotic events for all eligible participants. We screened individuals on these registers to identify those receiving methylphenidate treatment, and who were aged 12-30 years at the start of treatment, for their inclusion in the study. We used a within-individual design to compare the incidence of psychotic events in these individuals during the 12-week periods immediately before and after methylphenidate initiation. Longer term risk was assessed by comparing the incidence of psychotic events 12 weeks before methylphenidate initiation and during a 12-week period one calendar year before the initiation of methylphenidate with the incidence of these events during the 12-week period one calendar year after methylphenidate initiation. We estimated the incidence rate ratios (IRR) and 95% CIs of psychotic events after the initation of methylphenidate treatment, relative to the events before treatment, which were defined as any hospital visit (inpatient admission or outpatient attendance, based on data from the National Patient Register) because of psychosis, using the International Classification of Diseases version 10 definition. Analyses were stratified by whether the individual had a history of psychosis. Findings: We searched the Swedish Prescribed Drug Register to find eligible individuals who had received methylphenidate between Jan 1, 2007 and June 30, 2012. 61 814 individuals were screened, of whom 23 898 (38·7%) individuals were assessed and 37 916 (61·3%) were excluded from the study because they were outside of the age criteria at the start of treatment, they had immigrated, emigrated, or died during the study period, or because they were administered other ADHD medications. The median age at methylphenidate initiation was 17 years, and a history of psychosis was reported in 479 (2·0%) participants. The IRR of psychotic events in the 12-week period after initiation of methylphenidate treatment relative to that in the 12-week period before treatment start was 1·04 (95% CI 0·80-1·34) in adolescents and young adults without a history of psychosis and 0·95 (0·69-1·30) among those with a history of psychosis. Interpretation: Contrary to clinical concerns, we found no evidence that initiation of methylphenidate treatment increases the risk of psychotic events in adolescents and young adults, including in those individuals with a history of psychosis. Our study should reassure clinicians considering initiating methylphenidate treatment for ADHD in adolescents and young adults, and it challenges the widely held view in clinical practice that methylphenidate should be avoided, or its use restricted, in individuals with a history of psychosis. Funding: Swedish Research Council, National Institute of Mental Health, UK National Institute of Health Research Nottingham Biomedical Research Centre.

The lancet. Psychiatry · cohort or longitudinal · 45 citationsread the source →

Patients' and Parents' Needs, Attitudes, and Perceptions About Early Palliative Care Integration in Pediatric Oncology.

Importance: Early palliative care integration for cancer patients is now touted as the optimal care model, yet significant barriers often prevent its implementation. A perceived barrier, especially for pediatric oncology patients, is the notion that patients and their families may not need or want palliative care involvement early in the disease trajectory. Objective: To determine the perception of symptom burden early in treatment and assess attitudes toward early integration of palliative care in pediatric oncology patient-parent pairs. Design, setting, and participants: Novel but pretested survey tools were administered to 129 patient-parent dyads of hospital-based pediatric oncology ambulatory clinics and inpatient units between September 2011 and January 2015. All patient participants were aged between 10 and 17 years and were diagnosed as having an oncologic condition 1 month to 1 year before enrollment. Both the patient and the parent in the dyad spoke English, and all participating parents provided written informed consent. A convenience sample was used for selection, with participants screened when otherwise presenting at a participating site. A total of 280 eligible participants were approached for study inclusion, 258 of whom were enrolled in the study (92.1% positive response-rate). Main outcomes and measures: Degree of perceived suffering from early symptom-related causes, attitudes toward early palliative care integration, and patient-parent concordance. Statistical analysis included descriptive statistics, calculation of concordance, McNemar test results, and Cochran-Armitage trend test results. Results: Of the 129 patients in the dyads, 68 were boys, and 61 girls; of the 129 parents, 15 were men, and 114 women. Patients reported the following symptoms in the first month of cancer therapy: nausea (n = 109; 84.5%), loss of appetite (n = 97; 75.2%), pain (n = 96; 74.4%), anxiety (n = 77; 59.7%), constipation (n = 69; 53.5%), depression (n = 64; 49.6%), and diarrhea (n = 52; 40.3%). A large proportion of those reporting suffering indicated substantial suffering severity from specific symptoms (ie, a great deal or a lot) including nausea, 52.3% (57 of 109), loss of appetite, 50.5% (49 of 97), constipation 30.4% (21 of 69), pain 30.2% (29 of 96), anxiety 28.6% (22 of 77), depression 28.1% (18 of 64), and diarrhea 23.1% (12 of 52). Few children and parents expressed opposition to early palliative care involvement (2 [1.6%] and 8 [6.2%]) or perceived any detrimental effects on their relationship with their oncologist (6 [4.7%] and 5 [3.9%]), loss of hope (3 [2.3%] and 10 [7.8%]), or therapy interference (3 [2.3%] and 2 [1.6%], respectively). Intradyad concordance was low overall: 26% to 29% for exact concordance and 40% to 69% for agreement within 1 response category. Significant differences in patient-parent attitudes toward aspects of early palliative care included child participants being more likely than their parents (40.3% [n = 52] vs 17.8% [n = 23]) to indicate that palliative care would have been helpful for treating their symptoms (P < .001). Conclusions and relevance: Pediatric oncology patients experience a high degree of symptom-related suffering early in cancer therapy, and very few patients or parents in this study expressed negative attitudes toward early palliative care. Our findings suggest that pediatric oncology patients and families might benefit from, and are not a barrier to, early palliative care integration in oncology.

JAMA oncology · cohort or longitudinal · 148 citationsread the source →

Association of Race and Ethnicity With Late-Life Depression Severity, Symptom Burden, and Care.

Importance: Knowledge gaps persist regarding racial and ethnic variation in late-life depression, including differences in specific depressive symptoms and disparities in care. Objective: To examine racial/ethnic differences in depression severity, symptom burden, and care. Design, setting, and participants: This cross-sectional study included 25 503 of 25 871 community-dwelling older adults who participated in the Vitamin D and Omega-3 Trial (VITAL), a randomized trial of cancer and cardiovascular disease prevention conducted from November 2011 to December 2017. Data analysis was conducted from June to September 2018. Exposure: Racial/ethnic group (ie, non-Hispanic white; black; Hispanic; Asian; and other, multiple, or unspecified race). Main outcomes and measures: Depressive symptoms, assessed using the Patient Health Questionnaire-8 (PHQ-8); participant-reported diagnosis, medication, and/or counseling for depression. Differences across racial/ethnic groups were evaluated using multivariable zero-inflated negative binomial regression to compare PHQ-8 scores and multivariable logistic regression to estimate odds of item-level symptom burden and odds of depression treatment among those with diagnosed depression. Results: There were 25 503 VITAL participants with adequate depression data (mean [SD] age, 67.1 [7.1] years) including 12 888 [50.5%] women, 17 828 [69.9%] non-Hispanic white participants, 5004 [19.6%] black participants, 1001 [3.9%] Hispanic participants, 377 [1.5%] Asian participants, and 1293 participants [5.1%] who were categorized in the other, multiple, or unspecified race group. After adjustment for sociodemographic, lifestyle, and health confounders, black participants had a 10% higher severity level of PHQ-8 scores compared with non-Hispanic white participants (rate ratio [RR], 1.10; 95% CI, 1.04-1.17; P < .001); Hispanic participants had a 23% higher severity level of PHQ-8 scores compared with non-Hispanic white participants (RR, 1.23; 95% CI, 1.10-1.38; P < .001); and participants in the other, multiple, or unspecified group had a 14% higher severity level of PHQ-8 scores compared with non-Hispanic white participants (RR, 1.14; 95% CI, 1.04-1.25; P = .007). Compared with non-Hispanic white participants, participants belonging to minority groups had 1.5-fold to 2-fold significantly higher fully adjusted odds of anhedonia (among black participants: odds ratio [OR], 1.76; 95% CI, 1.47-2.11; among Hispanic participants: OR, 1.96; 95% CI, 1.43-2.69), sadness (among black participants: OR, 1.31; 95% CI, 1.07-1.60; among Hispanic participants: OR, 2.09; 95% CI, 1.51-2.88), and psychomotor symptoms (among black participants: OR, 1.77; 95% CI, 1.31-2.39; among Hispanic participants: OR, 2.12; 95% CI, 1.28-3.50); multivariable-adjusted odds of sleep problems and guilt appeared higher among Hispanic vs non-Hispanic white participants (sleep: OR, 1.24; 95% CI, 1.01-1.52; guilt: 1.84; 95% CI, 1.31-2.59). Among those with clinically significant depressive symptoms (ie, PHQ-8 score ≥10) and/or those with diagnosed depression, black participants were 61% less likely to report any treatment (ie, medications and/or counseling) than non-Hispanic white participants after adjusting for confounders (adjusted OR, 0.39; 95% CI, 0.27-0.56). Conclusions and relevance: In this cross-sectional study, significant racial and ethnic differences in late-life depression severity, item-level symptom burden, and depression care were observed after adjustment for numerous confounders. These findings suggest a need for further examination of novel patient-level and clinician-level factors underlying these associations.

JAMA network open · 78 citationsread the source →

Understanding cardiopulmonary resuscitation decision making: perspectives of seriously ill hospitalized patients and family members.

Background: To improve communication and decision making related to cardiopulmonary resuscitation (CPR), a greater understanding of the perspectives of hospitalized patients with advanced diseases and their family members are needed. Methods: In five Canadian hospitals, we administered a face-to-face questionnaire to older inpatients with end-stage cancer and advanced medical diseases and, where possible, to one of their family members, regarding information needs, the deliberation process, and their preferred decisional role. Findings: A total of 440 of 569 patients (78%) and 160 of 176 available caregivers (91%) agreed to participate. Most patients (61%) had thought about what treatment they wanted if their heart stopped, few patients (11.3%) could describe more than two components of CPR, and only 2.7% of patients thought that the success rate of CPR was < 10%. A minority of patients (34%) had discussed CPR with their physician; 37% did not want to discuss their preferences with their doctor. Patients who felt that end-of-life issues were relevant to them were 5.5 times more likely to want a discussion with the physician regarding resuscitation (odds ratio, 5.5; 95% confidence interval, 2.5 to 12.0). The preferred role in decision making was variable, but most patients (59.7%) and family members (81.6%) preferred some degree of shared decision making that included the family member. There were no significant differences between cancer and medical patients in their preferred decisional role. Interpretation: Seriously ill hospitalized patients have poor knowledge about CPR, and variable preferences for deliberation and their role in the decision-making process regarding their treatment. Strategies that improve understanding of CPR and foster discussions that involve patients, family members, and physicians in the decision-making process may improve the quantity and quality of communication and decision making about CPR.

Chest · cohort or longitudinal · 126 citationsread the source →

Barriers and facilitators to chronic pain self-management: a qualitative study of primary care patients with comorbid musculoskeletal pain and depression.

Objective: To identify barriers and facilitators to self-management of chronic musculoskeletal pain among patients with comorbid pain and depression. Design: A qualitative study using focus group methodology. Setting: Veteran Affairs (VA) and University primary care clinics. Patients: Recruited after participation in a clinical trial. Intervention: The Stepped Care for Affective Disorders and Musculoskeletal Pain (SCAMP) trial tested an intervention of optimized antidepressant therapy combined with a pain self-management program versus usual care for primary care patients with comorbid chronic pain and depression. Outcome measures: Thematic content analysis from focus group data was used to identify patient-perceived barriers and facilitators to self-management of chronic musculoskeletal pain. Results: Patients (N = 18) were 27 to 84 years old (M = 54.8), 61% women, 72% white, and 22% black. Barriers to pain self-management included: 1) lack of support from friends and family; 2) limited resources (e.g., transportation, financial); 3) depression; 4) ineffectiveness of pain-relief strategies; 5) time constraints and other life priorities; 6) avoiding activity because of fear of pain exacerbation; 7) lack of tailoring strategies to meet personal needs; 8) not being able to maintain the use of strategies after study completion; 9) physical limitations; and 10) difficult patient-physician interactions. Facilitators to improve pain self-management included 1) encouragement from nurse care managers; 2) improving depression with treatment; 3) supportive family and friends; and 4) providing a menu of different self-management strategies to use. Conclusions: Future research is needed to confirm these findings and to design interventions that capitalize on the facilitators identified while at the same time addressing the barriers to pain self-management.

Pain medicine (Malden, Mass.) · cohort or longitudinal · 179 citationsread the source →

Telemedicine Applications for Cancer Rehabilitation: Scoping Review.

Background: Cancer is a significant public health issue worldwide. Treatments such as surgery, chemotherapy, and radiation therapy often cause psychological and physiological side effects, affecting patients' ability to function and their quality of life (QoL). Physical activity is crucial to cancer rehabilitation, improving physical function and QoL and reducing cancer-related fatigue. However, many patients face barriers to accessing cancer rehabilitation due to socioeconomic factors, transportation issues, and time constraints. Telerehabilitation can potentially overcome these barriers by delivering rehabilitation remotely. Objective: The aim of the study is to identify how telemedicine is used for the rehabilitation of patients with cancer. Methods: This scoping review followed recognized frameworks. We conducted an electronic literature search on PubMed for studies published between January 2015 and May 2023. Inclusion criteria were studies reporting physical therapy telerehabilitation interventions for patients with cancer, including randomized and nonrandomized controlled trials, feasibility studies, and usability studies. In total, 21 studies met the criteria and were included in the final review. Results: Our search yielded 37 papers, with 21 included in the final review. Randomized controlled trials comprised 47% (n=10) of the studies, with feasibility studies at 33% (n=7) and usability studies at 19% (n=4). Sample sizes were typically 50 or fewer participants in 57% (n=12) of the reports. Participants were generally aged 65 years or younger (n=17, 81%), with a balanced gender distribution. Organ-specific cancers were the focus of 66% (n=14) of the papers, while 28% (n=6) included patients who were in the posttreatment period. Web-based systems were the most used technology (n=13, 61%), followed by phone call or SMS text messaging-based systems (n=9, 42%) and mobile apps (n=5, 23%). Exercise programs were mainly home based (n=19, 90%) and included aerobic (n=19, 90%), resistance (n=13, 61%), and flexibility training (n=7, 33%). Outcomes included improvements in functional capacity, cognitive functioning, and QoL (n=10, 47%); reductions in pain and hospital length of stay; and enhancements in fatigue, physical and emotional well-being, and anxiety. Positive effects on feasibility (n=3, 14%), acceptability (n=8, 38%), and cost-effectiveness (n=2, 9%) were also noted. Functional outcomes were frequently assessed (n=19, 71%) with tools like the 6-minute walk test and grip strength tests. Conclusions: Telerehabilitation for patients with cancer is beneficial and feasible, with diverse approaches in study design, technologies, exercises, and outcomes. Future research should focus on developing standardized methodologies, incorporating objective measures, and exploring emerging technologies like virtual reality, wearable or noncontact sensors, and artificial intelligence to optimize telerehabilitation interventions. Addressing these areas can enhance clinical practice and improve outcomes for remote rehabilitation with patients.

JMIR cancer · review · 17 citationsread the source →

What are the known effects of yoga on the brain in relation to motor performances, body awareness and pain? A narrative review.

Objective: The current body of literature was reviewed to evaluate the effects of yoga on the brain in relation to motor performance, body awareness and pain. Background: Yoga has been increasingly popular in the Western countries especially for its unique integration of the mind and body. Yoga has been studied more intensely in the last decade. Although it has been shown to improve cognitive functions, few studies have looked into the effects of yoga on improving motor performance, body awareness or pain and the possible underlying brain mechanisms associated with them. Methods: A search of the current literature was made using keywords such as: "yoga brain motor", "yoga brain pain", "effects yoga brain" and "effects yoga brain motor performance". The findings were then discussed in relation to motor performance, body awareness and pain and their reported mechanisms of action on the brain. Results: A total of 61 articles were selected, out of which 29 were excluded because they did not meet our criteria. A total of thirty-two articles were included in this review, which we further subdivided by focus: motor performance (n = 10), body awareness (n = 14) and pain (n = 8). Discussion: Our review shows that yoga has a positive effect on learning rate, speed and accuracy of a motor task by increasing attention and decreasing stress through a better control of sensorimotor rhythms. Yoga also seems to improve sensory awareness and interoception, regulate autonomic input, increase parasympathetic activity and promote self-regulation. Yoga was also shown to reduce the threat signal, increase pain tolerance, decrease pain unpleasantness and decrease the anxiety and distress associated with pain. Those changes are associated with the recruitment of specific brain areas such as the insula, the amygdala and the hippocampus. Conclusion: Based on the studies reviewed in this report, we found that the practice of yoga seems to facilitate motor learning, to increase body awareness and to decrease pain. These are associated with a wide variety of changes in terms of brain activity and structure. Further studies are necessary to reveal its precise mechanism of action on the brain and to validate its wider application in clinical settings.

Complementary therapies in medicine · review · 41 citationsread the source →

A review and content analysis of engagement, functionality, aesthetics, information quality, and change techniques in the most popular commercial apps for weight management.

Background: There are thousands of apps promoting dietary improvement, increased physical activity (PA) and weight management. Despite a growing number of reviews in this area, popular apps have not been comprehensively analysed in terms of features related to engagement, functionality, aesthetics, information quality, and content, including the types of change techniques employed. Methods: The databases containing information about all Health and Fitness apps on GP and iTunes (7,954 and 25,491 apps) were downloaded in April 2015. Database filters were applied to select the most popular apps available in both stores. Two researchers screened the descriptions selecting only weight management apps. Features, app quality and content were independently assessed using the Mobile App Rating Scale (MARS) and previously-defined categories of techniques relevant to behaviour change. Inter-coder reliabilities were calculated, and correlations between features explored. Results: Of the 23 popular apps included in the review 16 were free (70%), 15 (65%) addressed weight control, diet and PA combined; 19 (83%) allowed behavioural tracking. On 5-point MARS scales, apps were of average quality (Md = 3.2, IQR = 1.4); "functionality" (Md = 4.0, IQR = 1.1) was the highest and "information quality" (Md = 2.0, IQR = 1.1) was the lowest domain. On average, 10 techniques were identified per app (range: 1-17) and of the 34 categories applied, goal setting and self-monitoring techniques were most frequently identified. App quality was positively correlated with number of techniques included (rho = .58, p < .01) and number of "technical" features (rho = .48, p < .05), which was also associated with the number of techniques included (rho = .61, p < .01). Apps that provided tracking used significantly more techniques than those that did not. Apps with automated tracking scored significantly higher in engagement, aesthetics, and overall MARS scores. Those that used change techniques previously associated with effectiveness (i.e., goal setting, self-monitoring and feedback) also had better "information quality". Conclusions: Popular apps assessed have overall moderate quality and include behavioural tracking features and a range of change techniques associated with behaviour change. These apps may influence behaviour, although more attention to information quality and evidence-based content are warranted to improve their quality.

The international journal of behavioral nutrition and physical activity · review · 228 citationsread the source →

Addressing Intimate Partner Violence and Sexual Violence Among Adolescents: Emerging Evidence of Effectiveness

Intimate partner violence (IPV) and sexual violence (SV) are widespread among adolescents and place them on a lifelong trajectory of violence, either as victims or perpetrators. The aim of this review was to identify effective approaches to prevent adolescent IPV and SV and to identify critical knowledge gaps. The interventions reviewed in this article reflect the global focus on interventions addressing violence perpetrated by men against women in the context of heterosexual relationships. Interventions for girls and boys (10-19 years) were identified through electronic searches for peer-reviewed and gray literature such as reports and research briefs. Studies were excluded if they were published before 1990 or did not disaggregate participants and results by age. Programs were classified as "effective," "emerging," "ineffective," or "unclear" based on the strength of evidence, generalizability of results to developing country settings, and replication beyond the initial pilot. Programs were considered "effective" if they were evaluated with well-designed studies, which controlled for threats to validity through randomization of participants. A review of 142 articles and documents yielded 61 interventions, which aimed to prevent IPV and SV among adolescents. These were categorized as "parenting" (n = 8), "targeted interventions for children and adolescents subjected to maltreatment" (n = 3), "school based" (n = 31; including 10 interventions to prevent sexual assault among university students), "community based" (n = 16), and "economic empowerment" (n = 2). The rigor of the evaluations varies greatly. A good number have relatively weak research designs, short follow-up periods, and low or unreported retention rates. Overall, there is a lack of robust standardized measures for behavioral outcomes. Three promising approaches emerge. First, school-based dating violence interventions show considerable success. However, they have only been implemented in high-income countries and should be adapted and evaluated in other settings. Second, community-based interventions to form gender equitable attitudes among boys and girls have successfully prevented IPV or SV. Third, evidence suggests that parenting interventions and interventions with children and adolescents subjected to maltreatment hold promise in preventing IPV or SV by addressing child maltreatment, which is a risk factor for later perpetration or experience of IPV or SV. Results suggest that programs with longer term investments and repeated exposure to ideas delivered in different settings over time have better results than single awareness-raising or discussion sessions. However, lack of rigorous evidence limits conclusions regarding the effectiveness of adolescent IPV and SV prevention programs and indicates a need for more robust evaluation.

Journal of Adolescent Health · review · 413 citationsread the source →

Alzheimer’s Association Dementia Care Practice Recommendations

Alzheimer’s disease is a degenerative brain disease and the most common cause of dementia. Dementia is a syndrome—a group of symptoms—that has a number of causes. The characteristic symptoms include difficulties with memory, language, problem solving, and other cognitive skills that affect a person’s ability to perform everyday activities (Alzheimer’s Association, 2017). According to the Alzheimer’s Association 2017 Alzheimer’s Disease Facts and Figures, an estimated 5.5 million Americans are living with Alzheimer’s dementia. One in 10 people aged 65 years and older (10%) has Alzheimer’s dementia, and almost two-thirds of Americans with Alzheimer’s are women. In addition to gender differences, Alzheimer’s dementia affects racial and ethnic groups disproportionately. Compared to older white adults, African Americans are about twice as likely to have Alzheimer’s or other dementias, and Hispanics are approximately 1.5 times as likely (Alzheimer’s Association, 2017). Almost 60% of older adults with Alzheimer’s or other dementias reside in the community, only 25% of who live alone. As their disease progresses, people with Alzheimer’s or other dementias generally receive more care from family members, unpaid caregivers, and community-based and residential care providers. Forty-two percent of residents in assisted living communities have Alzheimer’s or other dementias (Caffrey et al., 2012; Zimmerman, Sloane, & Reed, 2014), and 61% of nursing home residents have moderate or severe cognitive impairment (Centers for Medicare and Medicaid Services, 2016). Further, by age 80, 75% of people with Alzheimer’s dementia are admitted to a nursing home, compared with only 4% of the general population (Arrighi, Neumann, Lieberburg, & Townsend, 2010). Since its inception, the Alzheimer’s Association has been a leader in outlining principles and practices of quality care for individuals living with dementia. Early on, the Guidelines for Dignity described goals for quality care, followed by Key Elements of Dementia Care and the Dementia Care Practice Recommendations, as more evidence became available. In this new iteration, the Alzheimer’s Association Dementia Care Practice Recommendationsoutline recommendations for quality care practices based on a comprehensive review of current evidence, best practice, and expert opinion. The Dementia Care Practice Recommendations were developed to better define quality care across all care settings, and throughout the disease course. They are intended for professional care providers who work with individuals living with dementia and their families in residential and community-based care settings. With the fundamentals of person-centered care as the foundation, the Dementia Care Practice Recommendations (see Figure 1) illustrate the goals of quality dementia care in the following areas: Person-centered care Detection and diagnosis Assessment and care planning Medical management Information, education, and support Ongoing care for behavioral and psychological symptoms of dementia, and support for activities of daily living Staffing Supportive and therapeutic environments Transitions and coordination of services Dementia Care Practice Recommendations. This article highlights the recommendations from all 10 articles in the Supplement Issue of The Gerontologist entitled, Alzheimer’s Association Dementia Care Practice Recommendations. Each article provides more detail about the specific recommendations, as well as the evidence and expert opinion supporting them. This supplement includes two areas that generally are not included in recommendations for providers in community and residential care settings, although these topics are frequently included in recommendations for physicians and other medical care providers—detection and diagnosis and ongoing medical management. Different from existing recommendations on these two topics, the articles are written for nonphysician care providers and address what these providers can do to help with these important aspects of holistic, person-centered dementia care. Throughout all of the articles, Alzheimer’s disease and dementia are used interchangeably. Care partner is used to refer to those people supporting individuals in the early stages of dementia, and caregivers is used to refer to those supporting individuals in the middle and late stages; care provider is used for paid professionals. Lastly, the closing article by Thornhill and Conant (2018) outlines the interplay of policy and practice rounds out the supplement. The Alzheimer’s Association is hopeful that these Recommendations will greatly inform and substantially influence dementia care standards, training, practice, and policy. Know the person living with dementia The individual living with dementia is more than a diagnosis. It is important to know the unique and complete person, including his/her values, beliefs, interests, abilities, likes, and dislikes—both past and present. This information should inform every interaction and experience. Recognize and accept the person’s reality It is important to see the world from the perspective of the individual living with dementia. Doing so recognizes behavior as a form of communication, thereby promoting effective and empathetic communication that validates feelings and connects with the individual in his/her reality. Identify and support ongoing opportunities for meaningful engagement Every experience and interaction can be seen as an opportunity for engagement. Engagement should be meaningful to, and purposeful for, the individual living with dementia. It should support interests and preferences, allow for choice and success, and recognize that even when the dementia is most severe, the person can experience joy, comfort, and meaning in life. Build and nurture authentic, caring relationships Persons living with dementia should be part of relationships that treat them with dignity and respect, and where their individuality is always supported. This type of caring relationship is about being present and concentrating on the interaction, rather than the task. It is about “doing with” rather than “doing for” as part of a supportive and mutually beneficial relationship. Create and maintain a supportive community for individuals, families, and staff A supportive community allows for comfort and creates opportunities for success. It is a community that values each person and respects individual differences, celebrates accomplishments and occasions, and provides access to and opportunities for autonomy, engagement, and shared experiences. Evaluate care practices regularly and make appropriate changes Several tools are available to assess person-centered care practices for people living with dementia. It is important to regularly evaluate practices and models, share findings, and make changes to interactions, programs, and practices as needed. Make information about brain health and cognitive aging readily available to older adults and their families Within their scope of practice and training, nonphysician care providers who work with older adults and their families in community or residential care settings should either talk with them or refer them to other experts for information about brain health, changes in cognition that commonly occur in aging, and the importance of lifestyle behaviors and other approaches to maintain brain health. They should suggest print and online sources of additional information as appropriate. Know the signs and symptoms of cognitive impairment, that signs and symptoms do not constitute a diagnosis of dementia, and that a diagnostic evaluation is essential for diagnosis of dementia All nonphysician care providers who work with older adults in community or residential care settings should be trained to recognize the signs and symptoms of cognitive impairment. They should be trained that signs and symptoms are not sufficient for a diagnosis of dementia and that a diagnostic evaluation must be conducted by a physician who can make the diagnosis. Listen for concerns about cognition, observe for signs and symptoms of cognitive impairment, and note changes in cognition that occur abruptly or slowly over time Depending on their scope of practice, training, and agency procedures, if any, nonphysician care providers who work with older adults in community or residential care settings should listen for older adults’ concerns about dementia and observe for signs and symptoms of cognitive impairment and changes in cognition. As appropriate and in accordance with agency procedures and respect for individuals’ privacy, nonphysician care providers should communicate with coworkers about observed signs and symptoms, changes in cognition, and concerns of older adults and family members about the older adult’s cognition. Depending on their scope of practice and training, they should encourage the older adult and family to talk with the individual’s physician about the signs and symptoms, changes in cognition, and older adult and family concerns. Develop and maintain routine procedures for detection of cognition and referral for diagnostic evaluation Administrators of organizations that provide services for older adults in community or residential care settings and self-employed care providers should develop and maintain routine procedures for assessment of cognition. They should, at a minimum, maintain an up-to-date list of local memory assessment centers and physicians, including neurologists, geriatricians, and geriatric psychiatrists, who can provide a diagnostic evaluation for older adults who do not have a primary care physician or have a primary care physician who does not provide such evaluations. Ideally, nonphysician care providers and organizations that work with older adults should partner with physicians, health plans, and health care systems to establish effective referral procedures to ensure that older adults with signs and symptoms of cognitive impairment can readily receive a diagnostic evaluation. Use a brief mental status test to detect cognitive impairmentonlyif: such testing is within the scope of practice of the nonphysician care provider, and the nonphysician care provider has been trained to use the test; and required consent procedures are known and used; and there is an established procedure for offering a referral for individuals who score below a preset score on the test to a physician for a diagnostic evaluation. Encourage older adults whose physician has recommended a diagnostic evaluation to follow through on the recommendation Within their scope of practice, training, and agency procedures, if any, nonphysician care providers who work with older adults in community or residential care settings and are aware that an older adult’s physician has recommended a diagnostic evaluation should encourage the older adult and family, if appropriate, to follow through on the recommendation. They should talk with the older adult and family about the reasons for and importance of getting a diagnostic evaluation and provide print and online sources of additional information. Support better understanding of a dementia diagnosis Within their scope of practice, training, and agency procedures, if any, nonphysician care providers who work with older adults in community or residential care settings and are aware that the older adult has received a dementia diagnosis but does not understand the diagnosis (or the older adult’s family does not understand the diagnosis) should encourage the older adult and family to talk with the diagnosing physician. The care provider should also offer print and online sources of additional information as appropriate. Perform regular, comprehensive person-centered assessments and timely interim assessments Assessments, conducted at least every 6 months, should prioritize issues that help the person with dementia to live fully. These include assessments of the individual and care partner’s relationships and subjective experience and assessment of cognition, behavior, and function, and Assessment is ongoing and and Use assessment as an opportunity for information education, and support Assessment provides an opportunity to understanding of dementia and the specific of the individual and care and to the quality of the therapeutic Assessment should and and in to community for education, information and Assessment includes an to the to the experience of the person living with dementia and their care assessment and care planning with a assessment and care planning are to address the of dementia. The person living with dementia, care and caregivers are members of the care planning A should be to and share information and to and from providers. Use and communication systems to the of person-centered information all care providers assessment is of only if is and shared with care providers for use in planning and care. must be and Encourage planning to and and to of all care including care and Early and ongoing of what including values, quality of and goals for care, are essential for person-centered care. The person living with and should be in all of the even when is The individual and family should be to health care members to provide ongoing and support about management and care. a holistic, person-centered to care and a to the support for living with dementia and their caregivers that the importance of individuals’ ongoing medical care to their and quality of care providers must a to care and ongoing support to the person living with dementia and their family They should work to existing to coordination of medical and care and a care can or of and and these with and an that living with dementia and their caregivers to support and care over the of the to understand the of medical providers in the care of living with dementia and the that they make to care care providers and family caregivers should work with medical providers a shared of care to support the person living with dementia. Know about common of aging and dementia and encourage living with dementia and their families to talk with the person’s physician about to at home or in residential care settings can a person living with dementia, and a diagnosis of dementia can make the and management of care providers should encourage living with dementia and their families to changes in health and to the person’s and to the physician know about difficulties they in and at home or in a residential care Encourage living with dementia and their families to use for common behavioral and psychological symptoms of dementia evidence are effective at behavioral and psychological symptoms of dementia. care providers should encourage with dementia and their families to these and support the use of when they are for the person’s and quality of are there are times when is for behavioral and psychological It is important for community care providers to understand that can have for the person living with dementia in and to help them and their family to accept such care providers should also understand the general principles for and more and encourage the person living with dementia and family caregivers to their medical providers for and to the of when appropriate. with the person living with dementia, the family, and the person’s physician to and a person-centered for medical and It is for living with dementia and their caregivers to have a in should a medical or such as an or the of a a in will help the person’s physician and community care providers provide care and support that the of the person living with dementia and for family members and care providers who have to make for the person a Encourage living with dementia and their families to care early Persons living with dementia and their caregivers should understand available for care the stages of Alzheimer’s early with the person’s physician and other care providers and the of the person and family across care settings can make the the of dementia more and support early in the disease to for the the early stages creates opportunities to in the and care and of individuals living with dementia and their family the individual’s care values and early in the disease can in planning the moderate and as well as at of life. Early individuals living with dementia a in they are for in the their caregivers of when Encourage care to work and In have been developed that individuals living with dementia and their family caregivers, rather than with each person This person-centered and validates the individual living with care values and the and of the important issues on, the individual with and for their care will an important part of their as the care Build that are to It is important to effective that is to the unique of families living with dementia, such as and or families living with dementia do not out or accept support from issues when and for out to these will to more effective that the unique of all care education, and support are times of are throughout the disease that have on care from early to middle to late new symptoms and behaviors in care and concerns about what to in the through the stages of dementia also about other of such as changes in living or care providers from to nursing home education, and support that the individual with values and these will be to caregivers as they make on of the individual living with dementia. Use to more families in of education, and support Supportive and that use as to those in of services are on the As to and more and help more These be in communities where caregivers and individuals living with dementia are with access to supportive Identify of the and that or behavioral and psychological symptoms for the person living with dementia and psychological symptoms of dementia from changes in the brain in to of the and this interplay a that a or an and affects the quality of of the person living with dementia. The of and to them for each person, meaning that assessment must be and practices that are and in the care and other are generally not to and so practices should be the that have been developed in residential settings and also have in community settings include and care Recognize that the required to practices across care settings Different practices a of in of and and and Depending on the practices developed in residential settings be for by caregivers in settings. to of to ensure that practices are used when and as and in ongoing care of that there is a for care providers as they to These over to the of the practice that are most effective for the person living with dementia. Develop systems for of practices and make changes as The and of living with dementia over and so practices to also to over is to assess the of the practice if or other Support for must recognize the the individual’s ability to perform the and the of cognitive impairment Dementia is a by in the ability to for supportive care over as with support for and and must address cognitive and as well as person-centered care practices when support for all only are respect, and choice a common across all care, but the in support is for must to the abilities, likes, and of the person living with dementia. support for to respect, and the and the In people living with dementia are more to for they are choice and and if they in support for to dignity and the the and health and In people living with dementia are more to be for they are for signs of or have regularly and access to a that is as and and in the support for to respect and the the health and and and and In people living with dementia are more likely to for they are with and in a and maintain health, are and and and appropriate a and for new as well as ongoing A comprehensive should be that includes the and values, and person-centered dementia This is essential for new and should be included in ongoing for all staff Develop systems for and person-centered information It is important that all staff know the person living with dementia as an procedures for person-centered information that includes preferences, and It is also essential that an effective be developed to share this information with all Encourage communication, and should staff and through and is most effective when to include ongoing education, communication and and on all is and will and relationships an caring and supportive a person-centered is not and It is also that the be and know that staff are the of success, and when staff are and they in will more likely and and encourage and family relationships relationships living with dementia, staff and families is to person-centered care, and is in part by staff The of all in planning care, education, and relationships as Evaluate systems and for It is important that an and evaluate information on all staff including and of the should be used to evaluate the of all systems and areas for In should share this information with and the Create a of community within the care The care community includes the person care, their family and other care and professional care providers. The should support relationships with as a of common interests, and the goals of the individuals living with dementia, their caregivers, and other care providers. comfort and dignity for in the care community It is important that members of the care community are to live and work in a of and mental comfort from or are to maintain of and through that support to and Support and within the care community of the care community should and respect in their and behavior each Doing so includes a supportive that does not on individuals and them and also their The for and cognitive changes by and supporting opportunities for choice for all in the care community The of the care community a of opportunities for all to make their and professional as well as their health and The can provide opportunities for and the individual’s to make for opportunities for meaningful engagement to members of the care community are on the person, is based on that provides opportunities to in activities with and the or of meaningful and living with dementia and their family caregivers about common in care and living with dementia and their care about in care should occur and family caregivers are to the care of individuals living with dementia, is important to understand their for information about common including across care settings, such as home to or nursing nursing home to within care settings, such as from an to an care or from of or care providers to tools are available from the Alzheimer’s Disease and and the Alzheimer’s Association that can be to living with dementia and their caregivers to help them for the of and to care settings such as nursing or assisted complete and timely communication of information across and within settings living with dementia are frequently across essential information. is essential to ensure a timely and to share medical and care planning caregivers and providers throughout is needed. health across care settings also this communication across settings, and within organizations or practices is essential written and living with dementia and their caregivers in and information in a and can help to with in care and must be appropriate in should be by a to the of care. these by or approaches to communicate can the of information and of Evaluate the and goals of the person living with dementia the of in care and goals for care, including preferences, and and living the person living with dementia can is essential in care. a person living with dementia is to including caregivers or who know the person well is or other a in care or of care, a review and of the and goals of the person living with dementia should include an assessment of health and ability to the of the person living with dementia. This of the in goals of care and more effective to ensure appropriate assessments are the to a person with dementia to of care is Create environments to living with dementia and their care as they make of a to support the person living with dementia throughout in care is Each of the to have a of in the fundamentals of caring for individuals living with dementia at all stages and their family All of the described were to address the for individuals living with dementia and other as well as the of their family in the were trained in dementia care management over a of in and developed a of on to the care of older adults living with dementia and their family as they from the to this type of work of the to support the person living with dementia and their family as they providers and across Every of the health care must be and to ensure the timely and appropriate of to the or of care. from the of care should maintain for individuals with dementia the caregivers at the to or in care The of care in this review on as or or supporting in residential care settings as nursing or assisted living have or the of living with dementia, of these should be to the that and is important to note that these are to or for living with dementia has the to more common with this population such as of and As of care are and to the of living with dementia across and within settings of care is to share the from these in care The Alzheimer’s Association is the health in Alzheimer’s care, and in by a group of family caregivers and individuals in the Association includes a home in a policy in and a in communities across the an estimated million people are living with dementia. In the more than million have and over million are as their The Alzheimer’s Association this by and support to the who dementia every of a This as part of a supplement and by the Alzheimer’s These recommendations the individual recommendations developed by of the included in the Supplement Issue of The Gerontologist entitled, Alzheimer’s Association Dementia Care Practice and

The Gerontologist · editorial or comment · 230 citationsread the source →

The pleasure of art as a matter of fact

You have accessMoreSectionsView PDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditEmail Cite this article Nadal Marcos and Skov Martin 2018The pleasure of art as a matter of factProc. R. Soc. B.2852017225220172252http://doi.org/10.1098/rspb.2017.2252SectionYou have accessCommentThe pleasure of art as a matter of fact Marcos Nadal Marcos Nadal http://orcid.org/0000-0002-9341-4688 Department of Psychology, University of the Balearic Islands, Palma de Mallorca 07122, Spain [email protected] Google Scholar Find this author on PubMed Search for more papers by this author and Martin Skov Martin Skov Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Copenhagen 2650, Denmark Center for Decision Neuroscience, Copenhagen Business School, Copenhagen 2000, Denmark Google Scholar Find this author on PubMed Search for more papers by this author Marcos Nadal Marcos Nadal http://orcid.org/0000-0002-9341-4688 Department of Psychology, University of the Balearic Islands, Palma de Mallorca 07122, Spain [email protected] Google Scholar Find this author on PubMed and Martin Skov Martin Skov Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Copenhagen 2650, Denmark Center for Decision Neuroscience, Copenhagen Business School, Copenhagen 2000, Denmark Google Scholar Find this author on PubMed Published:21 March 2018https://doi.org/10.1098/rspb.2017.2252All other forms of perception divide a man, because they are exclusively based either on the sensuous or on the intellectual part of his being; only the perception of the Beautiful makes something whole of him, because both his natures must accord with it.— Schiller, 1793–1795, Letters on the Aesthetic Education of Man, p. 138, Letter 27Can art make us better people? Better members of society? In her recent article, 'Pleasure junkies all around! Why it matters and why "the arts" might be the answer: a biopsychological perspective', Christensen [1] claims that engaging with art can promote healthy choices, choices that balance short-term pleasure goals with long-term general well-being. She suggests that many modern life conveniences, such as social media, computer games or online shopping, have the potential to turn us into 'pleasure junkies' because they maximize short-term pleasures. But art, Christensen argues, is a safe choice and a means to remedy this unhealthy addiction to pleasure. Christensen's argument is grounded on three claims about the sort of pleasure we get from art. First, in contrast to low-level pleasure, which Christensen conceives as 'a mere perceptual stimulation leading to a rewarding sensation (food, sex, etc.)' ([1], p. 2), pleasure from art is presented as a kind of higher-order pleasure that engages 'broader neural networks implied in the attribution of meaning' (p. 2), presumably leading to 'long-term maintenance of healthy bodily function' (p. 2). Second, 'the arts do not induce states of craving without fulfilment—as do activities with reinforcement schedules which are prone to create habits and addictions such as intermittent variable ratio or interval reinforcement schedules (e.g. social media, gambling, football, extreme sports, drugs' (p. 4). Third, 'the arts do not search for a perceptual "Bliss point" […]. They do not just repeat over and over again a sensory stimulus that excites the senses and induces craving for more of a "pleasurable itch" (e.g. sugar, sexualized body displays, certain musical lyrics, tones; i.e. a perceptual "bliss point")' (p. 4).The claim, in a nutshell, is that the pleasure induced by art is different to the pleasure induced by food, sex, sports or drugs, because it is related to the balanced activation of brain systems related to short-term pleasure and long-term wellbeing goals, because it does not induce craving, and because it is not aimed at a perceptual 'bliss point'. This distinct sort of pleasure, according to Christensen, makes it possible for the arts to thwart the pernicious effects that the unhealthy urges and cravings licensed by 'today's mainstream acceptance of pleasure-seeking behaviour' (p. 5) have on individuals' lives and on societies. Such sweeping statements about art, food, sex, sports and society as a whole merit close examination. Christensen's primary claim that the pleasure induced by art is of a special kind, different to the pleasure induced by other activities is not supported by current understanding of what pleasure is. It is, moreover, contradicted by abundant empirical evidence. This evidence shows that pleasures, whatever their source, owe to activity in the same mesocorticolimbic circuit [2] and are encoded as a common neural currency [3]. As Kent Berridge and Morten Kringelbach put it: 'the brain mechanisms involved in fundamental pleasures (food and sexual pleasures) overlap with those for higher-order pleasures (e.g. monetary, artistic, musical, altruistic and transcendent pleasures) […] From sensory pleasures and drugs of abuse […] to monetary, aesthetic and musical delights, all pleasures seem to involve the same hedonic brain systems' ([4], p. 481). Thus, there is no evidence for specific brain regions or neural circuits related to the pleasure from art. Rather, the appreciation of art relies on brain mechanisms that evolved to appraise the value of biologically relevant objects in relation to internal homeostatic states [5]: 'Emotional reactions to music, further, activate the same cortical, subcortical and autonomic circuits, which are considered as the essential survival circuits of biological organisms in general' ([6], p. 6). In sum, the evidence shows that pleasure elicited by music and other art forms is no different in genesis and function to the pleasure induced by food, drugs and sex [7,8]. This is a matter of fact, not opinion. What supports Christensen's argument if not empirical evidence? In our view, her argument for the distinctness of art-induced pleasure seems based upon an oversimplified and devaluing conception of the pleasures of sex, food and sports, and a very narrow notion of art and its function. Christensen presents food, sex and sports as meaningless low-level sources of pleasure, and the arts as privileged vehicles for meaningful experiences. It is the personal and meaningful engagement with art—Christensen suggests—that fosters a balanced activation of brain systems related to short-term pleasure and long-term well-being goals. However, rarely—if ever—are food, sex and sports meaningless rewarding sensations. Contrary to Christensen's definition on page 2 of her article, pleasure—even sensory pleasure—is not simply reward, and never simply a sensation [4]. Indulging in food, sex or sports are meaningful and personally significant experiences that are not a matter of mere physical sensation. The experience of pleasure from food and sex is shaped by context, knowledge, expectations, anticipations, attitudes and beliefs that bring meaning to them [9–11]. Sex can be meaningful because it signifies physical connection with one's loved one, because it is cheating on someone, or deemed a sin. Likewise, eating is not about obtaining low-level pleasure. What we eat, the way we eat, what we believe about what we eat, where and whom we eat with, imbue eating with individual and social meaning, and shape the actual pleasure of eating [12]. On the other hand, encounters with art are not necessarily meaningful [13,14]. Actually, there is nothing intrinsically meaningful about engaging with art. Many laypeople lack the knowledge schemata required to engage meaningfully with abstract, cubist or contemporary art [15,16]. There are plenty of artworks people do not find meaningful or pleasant. Meaning making is not a special feature of art; it is a general feature of our species's cognition [17,18]. We can endow virtually any aspect of reality with meaning: sex, food, sports, a urinal, the shape of a cloud, an averted glance, someone's absence. Christensen's argument also rests on a historically and culturally narrow conception of art and its function. Art is presented as a circumscribed category of activities that elicit a unique sort of pleasant experiences: — The arts are set of activities of a special kind that share certain defining features distinguishing them from other activities: 'the arts push boundaries, surprise, reveal and excite both artist and spectator' ([1], p. 4).— Art encounters are positive, leading to 'pleasurable chills' and pleasurable experiences of understanding: 'The moment of meaning-assignation, also called "mastering" or "understanding" an artwork, is therefore a pleasurable experience' ([1], p. 4).— The pleasure elicited by art is special, because it does not involve craving for intense peaks: 'The arts do not search for a perceptual "bliss point" […] They do not just repeat over and over a sensory stimulus that excites the senses and induces craving for more of a "pleasurable itch"' ([1], p. 4).This characterization of the arts substantially overlaps with the notion of 'fine arts'. The core features of this characterization were instituted in the eighteenth century, after European intellectuals grouped certain activities into a distinct and autonomous collection, labelled 'fine arts'. To make sense of and promote this grouping, it became imperative to identify a common essence setting art apart from other activities [19,20,21]. One of the most popular proposals was that only art could produce a special sort of pleasure, sophisticated and polite [19,21]—a conception stemming not from any understanding of physiology, but from mere speculation. This limited historical and cultural scope renders this conception of the arts unfit for behavioural or neuroscientific research [19]. The category 'the arts' should not be mistaken for a natural kind. It is a historical convention, and has no direct biological correspondence. Moreover, this conception of art that Christensen espouses does not apply to art as practised in non-Western societies [19,22]. It does not even apply to Western art before the eighteenth century or after the nineteenth century [19,20,21]. First, art does not necessarily evoke pleasurable experiences. There are abundant artworks intended to arouse negative emotions [19,23], and to portray physical and moral ugliness [24]. Understanding art is not necessarily a pleasant experience: it can be an angering, disgusting or upsetting one [25]. Second, many artworks actually exploit repetition, bliss points and craving [26]. Repetition is a fundamental design feature of music and other performance arts [27]: In Relation in Space (1976) Marina Abramovic and Ulay ran into each other repeatedly for an hour; Ravel's Bolero is a 17 min-long instance of melodic and rhythmic repetitiveness. Anticipation and craving for bliss points are also essential to music [28]. In fact, the enjoyment of music is linked to intense feelings of anticipation and expectation caused by dopamine activity in the caudate nucleus (also involved in the rewarding aspect of food) [29,30], and peak pleasure states (bliss points) [31], caused by the release of dopamine and opioids in the brain's reward system (also involved in cocaine induced euphoria) [29,30]. Given the available evidence, therefore, there is no reason to believe that the pleasure from art is special or unique [32].In sum, Christensen's claim for the distinctiveness of pleasure from art is contradicted by empirical evidence, and her argument for the beneficial effects of art rests upon disputed foundations. Art's capacity to promote healthier choices and make us better people that can contribute to a better society remains as unconfirmed today as it was when Schiller speculated on art's power to harmonize human's conflicting sensuous and formal impulses. Christensen's argument is problematic even if intended to highlight hypothetical possibilities. Arguments about hypothetical possibilities should still rely on valid premises, and scientific hypotheses should be grounded on evidence, or at least in line with it. Otherwise, they are merely unfounded speculations. Scientific aesthetics is only just finding its footing and its place within cognitive neuroscience [33,34]. If evidence is ignored or rejected because it does not fit preconceived notions about art and its function, scientific aesthetics will become only an arena to promote and legitimize personally appealing notions of art by applying a scientific gloss over them. A proper scientific study of art needs to be grounded on empirical evidence and strong arguments that follow from solid premises [35,36]. Only then can scientific aesthetics provide reliable explanations for artistic and aesthetic behaviour, and thus make a significant contribution to the understanding of our human nature. Data accessibilityThis article has no additional data. Authors' contributionsBoth authors have contributed to conceiving, developing and writing the research presented in this paper, and approved it for publication. Competing interestsWe declare we have no competing interests. FundingThis research was supported by grant PSI2016-77327-P (MINECO/AEI/ERDF, EU).Footnotes© 2018 The Author(s)Published by the Royal Society. All rights reserved. References1Christensen JF. 2017Pleasure junkies all around! Why it matters and why 'the arts' might be the answer: a biopsychological perspective. Proc. R. Soc. B 284, 20162837. (doi:10.1098/rspb.2016.2837) Link, ISI, Google Scholar2Berridge CW, Kringelbach ML. 2013Neuroscience of affect: brain mechanisms of pleasure and displeasure. Curr. Opin. Neurobiol. 23, 294–303. (doi:10.1016/j.conb.2013.01.017) Crossref, PubMed, ISI, Google Scholar3Levy DJ, Glimcher PW. 2012The root of all value: a neural common currency for choice. Curr. Opin. Neurobiol. 22, 1027–1038. (doi:10.1016/j.conb.2012.06.001) Crossref, PubMed, ISI, Google Scholar4Kringelbach ML, Berridge KC. 2009Towards a functional neuroanatomy of pleasure and happiness. Trends Cogn. Sci. 13, 479–487. (doi:10.1016/j.tics.2009.08.006) Crossref, PubMed, ISI, Google Scholar5Brown S, Gao X, Tisdelle L, Eickhoff LM. 2011Naturalizing aesthetics: brain areas for aesthetic appraisal across sensory modalities. Neuroimage 58, 250–258. (doi:10.1016/j.neuroimage.2011.06.012) Crossref, PubMed, ISI, Google Scholar6Reybrouck M, Eerola T. 2017Music and its inductive power: a psychobiological and evolutionary approach to musical emotions. Front. Psychol. 8, 494. (doi:10.3389/fpsyg.2017.00494) Crossref, PubMed, ISI, Google Scholar7Blood AJ, Zatorre RJ. 2001Intensely pleasurable responses to music correlate with activity in brain regions implicated in reward and emotion. Proc. Natl Acad. Sci. USA 98, 11 818–11 823. (doi:10.1073/pnas.191355898) Crossref, ISI, Google Scholar8Mallik A, Chandra ML, Levitin DJ. 2017Anhedonia to music and mu-opioids: evidence from the administration of naltrexone. Sci. Rep. 7, 41952. (doi:10.1038/srep41952) Crossref, PubMed, ISI, Google Scholar9Barrett LF. 2015How emotions are made: the secret life of the brain. London, UK: Macmillan. Google Scholar10Bloom P. 2010How pleasure works: the new science of why we like what we like. New York, NY: Norton. Google Scholar11Chatterjee A. 2014The aesthetic brain: how we evolved to desire beauty and enjoy art. New York, NY: Oxford University Press. Google Scholar12Spence C. 2017Gastrophysics: the new science of eating. London, UK: Penguin. Google Scholar13Leder H, Belke B, Oeberst A, Augustin D. 2004A model of aesthetic appreciation and aesthetic judgments. Br. J. Psychol. 95, 489–508. (doi:10.1348/0007126042369811) Crossref, PubMed, ISI, Google Scholar14Vessel EA, Rubin N. 2010Beauty and the beholder: highly individual taste for abstract, but not real-world images. J. Vis. 10, 1–14. (doi:10.1167/10.2.18) Crossref, PubMed, ISI, Google Scholar15Minissale G. 2013The psychology of contemporary art. Cambridge, UK: Cambridge University Press. Crossref, Google Scholar16Muth C, Pepperell R, Carbon C-C. 2013Give me Gestalt! Preference for cubist artworks revealing high detectability of objects. Leonardo 46, 488–489. (doi:10.1162/LEON_a_00649) Crossref, ISI, Google Scholar17Deacon TW. 1997The symbolic species: the co-evolution of language and the brain. New York, NY: Norton. Google Scholar18Henshilwood CS, d'Errico F. 2011Homo symbolicus: the dawn of language, imagination and spirituality. Amsterdam, The Netherlands: John Benjamins Publishing Co. Crossref, Google Scholar19Carroll N. 2008Aesthetic experience, art and artists. In Aesthetic experience (eds Shusterman R, Tomlin A), pp. 145–165. New York, NY: Routledge. Google Scholar20Kivy P. 2012What really happened in the eighteenth century: the 'Modern System' re-examined (again). Br. J. Aesthetics 52, 61–74. (doi:10.1093/aesthj/ayr046) Crossref, ISI, Google Scholar21Shiner L. 2001The invention of art: a cultural history. Chicago, IL: University of Chicago Press. Crossref, Google Scholar22Anderson RL. 1989Art in small-scale societies. 2nd edn. Englewood Cliffs, NJ: Prentice Hall. Google Scholar23Silvia PJ. 2009Looking past pleasure: anger, confusion, disgust, pride, surprise, and other unusual aesthetic emotions. Psychol. Aesthetics Creat. Arts 3, 48–51. (doi:10.1037/a0014632) Crossref, ISI, Google Scholar24Eco U. 2007On ugliness. London, UK: Harvill Secker. Google Scholar25Silvia PJ, Brown EM. 2007Anger, disgust, and the negative aesthetic emotions: expanding an appraisal model of aesthetic experience. Psychol. Aesthetics Creat. Arts 1, 100–106. (doi:10.1037/1931-3896.1.2.100) Crossref, Google Scholar26Huron D. 2006Sweet anticipation: music and the psychology of expectation. Cambridge, MA: MIT Press. Crossref, Google Scholar27Fitch W. 2006The biology and evolution of music: a comparative perspective. Cognition 100, 173–215. (doi:10.1016/j.cognition.2005.11.009) Crossref, PubMed, ISI, Google Scholar28Trainor LJ, Zatorre RJ. 2009The neurobiological basis of musical expectations. In The Oxford handbook of music psychology (eds Hallam S, Cross I, Thaut M), pp. 171–183. Oxford, UK: Oxford University Press. Google Scholar29Salimpoor VN, Benovoy M, Larcher K, Dagher A, Zatorre RJ. 2011Anatomically distinct dopamine release during anticipation and experience of peak emotion to music. Nat. Neurosci. 14, 257–262. (doi:10.1038/nn.2726) Crossref, PubMed, ISI, Google Scholar30Salimpoor VN, Zatorre RJ. 2013Neural interactions that give rise to musical pleasure. Psychol. Aesthetics Creat. Arts 7, 62–75. (doi:10.1037/a0031819) Crossref, ISI, Google Scholar31Whaley J, Sloboda J, Gabrielsson A. 2009Peak experiences in music. In The Oxford handbook of music psychology (eds Hallam S, Cross I, Thaut M), pp. 452–461. Oxford, UK: Oxford University Press. Google Scholar32Skov M, Nadal M.In press. Art is not special: an assault on the last lines of defense against the naturalization of the human mind. Rev. Neurosci. (doi:10.1515/revneuro-2017-0085) ISI, Google Scholar33Chatterjee A. 2011Neuroaesthetics: a coming of age story. J. Cogn. Neurosci. 23, 53–62. (doi:10.1162/jocn.2010.21457) Crossref, PubMed, ISI, Google Scholar34Pearce MT, Zaidel DW, Vartanian O, Skov M, Leder H, Chatterjee A, Nadal M. 2016Neuroaesthetics: the cognitive neuroscience of aesthetic experience. Perspect. Psychol. Sci. 11, 265–279. (doi:10.1177/1745691615621274) Crossref, PubMed, ISI, Google Scholar35Nadal M, Vartanian O, Skov M. 2017Psychological models of art reception must be empirically grounded. Behav. Brain Sci. 40, 36–37. (doi:10.1017/S0140525X17001790) Crossref, ISI, Google Scholar36Nadal M, Skov M. 2017Top–down and bottom–up: front to back: comment on 'Move me, astonish me… delight my eyes and brain: the Vienna integrated model of top–down and bottom–up processes in Art Perception (VIMAP) and corresponding affective, evaluative, and neurophysiological correlates' by Matthew Pelowski et al. Phys. Life Rev. 21, 148–149. (doi:10.1016/j.plrev.2017.06.013) PubMed, ISI, Google Scholar Previous ArticleNext Article VIEW FULL TEXT DOWNLOAD PDF FiguresRelatedReferencesDetailsCited by Clemente A, Pearce M, Skov M and Nadal M (2021) Evaluative judgment across domains: Liking balance, contour, symmetry and complexity in melodies and visual designs, Brain and Cognition, 10.1016/j.bandc.2021.105729, 151, (105729), Online publication date: 1-Jul-2021. Chuan-Peng H, Huang Y, Eickhoff S, Peng K and Sui J (2020) Seeking the "Beauty Center" in the Brain: A Meta-Analysis of fMRI Studies of Beautiful Human Faces and Visual Art, Cognitive, Affective, & Behavioral Neuroscience, 10.3758/s13415-020-00827-z, 20:6, (1200-1215), Online publication date: 1-Dec-2020. Skov M and Nadal M (2020) A Farewell to Art: Aesthetics as a Topic in Psychology and Neuroscience, Perspectives on Psychological Science, 10.1177/1745691619897963, 15:3, (630-642), Online publication date: 1-May-2020. Kalpokas I (2019) Making the Theory Political A Political Theory of Post-Truth, 10.1007/978-3-319-97713-3_4, (87-121), . Kalpokas I (2019) Affective Encounters of the Algorithmic Kind: Post-Truth and Posthuman Pleasure, Social Media + Society, 10.1177/2056305119845678, 5:2, (205630511984567), Online publication date: 1-Apr-2019. Skov M (2019) Aesthetic Appreciation: The View From Neuroimaging, Empirical Studies of the Arts, 10.1177/0276237419839257, 37:2, Online publication date: H, I and (2020) A for We Aesthetic in Human Neuroscience, A and in A New for Arts, This March Article in 2018 The Author(s)Published by the Royal Society. All rights Citations and are available with

Proceedings of the Royal Society B Biological Sciences · editorial or comment · 24 citationsread the source →

Generation lengths of the world's birds and their implications for extinction risk.

Birds have been comprehensively assessed on the International Union for Conservation of Nature (IUCN) Red List more times than any other taxonomic group. However, to date, generation lengths have not been systematically estimated to scale population trends when undertaking assessments, as required by the criteria of the IUCN Red List. We compiled information from major databases of published life-history and trait data for all birds and imputed missing life-history data as a function of species traits with generalized linear mixed models. Generation lengths were derived for all species, based on our modeled values of age at first breeding, maximum longevity, and annual adult survival. The resulting generation lengths varied from 1.42 to 27.87 years (median 2.99). Most species (61%) had generation lengths <3.33 years, meaning that the period of 3 generations-over which population declines are assessed under criterion A-was <10 years, which is the value used for IUCN Red List assessments of species with short generation times. For these species, our trait-informed estimates of generation length suggested that 10 years is a robust precautionary value for threat assessment. In other cases, however, for whole families, genera, or individual species, generation length had a substantial impact on their estimated extinction risk, resulting in higher extinction risk in long-lived species than in short-lived species. Although our approach effectively addressed data gaps, generation lengths for some species may have been underestimated due to a paucity of life-history data. Overall, our results will strengthen future extinction-risk assessments and augment key databases of avian life-history and trait data.

Conservation biology : the journal of the Society for Conservation Biology · 147 citationsread the source →

Implementation of an infant male circumcision programme, Pakistan.

Objective: To retrospectively review outcomes of a health provider-led infant circumcision programme in Pakistan. Methods: Based on World Health Organization guidelines, we trained surgical technicians and midwives to perform circumcisions using the Plastibell device at two Indus Health Network facilities. Programme tools include a training manual for health providers, information brochures for families, an enrolment form and standardized forms for documenting details of the procedure and outcomes. Infants aged 1-92 days were eligible for the study. Health workers contacted families on days 1 and 7 after the procedure to record any adverse events. We compared the characteristics of infants experiencing adverse events with infants facing no complications using multivariate logistic regression. Findings: Between August 2016 and August 2018, 2822 circumcised male infants with mean age 22.8 days were eligible for the study. Of these, 2617 infants (92.7%) were followed up by telephone interviews of caretakers. Older infants were more likely to experience adverse events than infants circumcised between 1-30 days of age: 31-60 days: adjusted odds ratio, aOR: 2.03; 95% confidence interval, CI: 1.31-3.15; 61-92 days: aOR: 2.14; 95% CI: 1.13-4.05. Minor adverse events (100 infants; 3.8%) included failure of the bell to shed (90 infants) and minimal bleeding (10 infants). Major adverse events (eight infants; 0.3%) included bleeding that required intervention (four infants), infection (three infants) and skin tear (one infant). Conclusion: Standardized training protocols and close monitoring enabled nonphysician health providers to perform safe circumcisions on infants aged three months or younger.

Bulletin of the World Health Organization · 6 citationsread the source →

What General and Pain-associated Psychological Distress Phenotypes Exist Among Patients with Hip and Knee Osteoarthritis?

Background: Psychological distress can negatively influence disability, quality of life, and treatment outcomes for individuals with hip and knee osteoarthritis (OA). Clinical practice guidelines recommend a comprehensive disease management approach to OA that includes the identification, evaluation, and management of psychological distress. However, uncertainty around the best psychological screening and assessment methods, a poor understanding of the heterogeneity of psychological distress in those with OA, and lack of guidance on how to scale treatment have limited the growth of OA care models that effectively address individual psychological needs. Questions/purposes: (1) Across which general and pain-related psychological distress constructs do individuals seeking conservative care for hip or knee OA report higher scores than the general population of individuals seeking conservative care for musculoskeletal pain conditions? (2) What common psychological phenotypes exist among nonsurgical care-seeking individuals with hip or knee OA? Methods: The sample included participants from the Duke Joint Health Program (n = 1239), a comprehensive hip and knee OA care program, and the Optimal Screening for Prediction of Referral and Outcome (OSPRO) cohort studies (n = 871) comprising individuals seeking conservative care for knee, shoulder, low back, or neck pain. At the initial evaluation, patients completed the OSPRO Yellow Flag (OSPRO-YF) Assessment Tool, which assesses 11 general and pain-related psychological distress constructs (depression, anxiety, fear of movement, self-efficacy for managing one's own pain). We used OSPRO-YF scores to compare levels of psychological distress between the cohorts. Cohen's d effect sizes were calculated to determine the magnitude of differences between the groups, with d = 0.20, d = 0.50, and d = 0.80 indicating small, medium, and large effect sizes, respectively. We used a latent class analysis to derive psychological distress phenotypes in people with OA based on the 11 OSPRO-YF psychological distress indicators. Psychological distress phenotypes are characterized by specific mood, belief, and behavioral factors that differentiate subgroups within a population. Phenotyping can help providers develop scalable treatment pathways that are better tailored to the common needs of patients. Results: Patients with OA demonstrated higher levels of general and pain-related psychological distress across all psychological constructs except for trait anxiety (that is, anxiety level as a personal characteristic rather than as a response to a stressful situation, like surgery) with small-to-moderate effect sizes. Characteristics with the largest effect sizes in the OA and overall OSPRO cohort were (Cohen's d) general anxiety (-0.66, lower in the OA cohort), pain catastrophizing (the tendency to ruminate over, maginfiy, or feel helpless about a pain experience, 0.47), kinesiophobia (pain-related fear of movement, 0.46), pain self-efficacy (confidence in one's own ability to manage his or her pain, -0.46, lower in the OA cohort), and self-efficacy for rehabilitation (confidence in one's own ability to perform their rehabilitation treatments, -0.44, lower in the OA cohort). The latent class analysis yielded four phenotypes (% sample): high distress (52%, 647 of 1239), low distress (26%, 322 of 1239), low self-efficacy and acceptance (low confidence in managing and willingness to accept pain) (15%, 186 of 1239), and negative pain coping (exhibiting poor pain coping skills) (7%, 84 of 1239). The classification error rate was near zero (2%), and the median of posterior probabilities used to assign subgroup membership was 0.99 (interquartile range 0.98 to 1.00), both indicating excellent model performance. The high-distress group had the lowest mean age (61 ± 11 years) and highest levels of pain intensity (6 ± 2) and disability (HOOS JR: 50 ± 15; KOOS JR: 47 ± 15), whereas the low-distress group had the highest mean age (63 ± 10 years) and lowest levels of pain (4 ± 2) and disability (HOOS JR: 63 ± 15; KOOS JR: 60 ± 12). However, none of these differences met or exceeded anchor-based minimal clinically important difference thresholds. Conclusions: General and pain-related psychological distress are common among individuals seeking comprehensive care for hip or knee OA. Predominant existing OA care models that focus on biomedical interventions, such as corticosteroid injection or joint replacement that are designed to directly address underlying joint pathology and inflammation, may be inadequate to fully meet the care-related needs of many patients with OA due to their underlying psychological distress. We believe this because biomedical interventions do not often address psychological characteristics, which are known to influence OA-related pain and disability independent of joint pathology. Healthcare providers can develop new comprehensive hip and knee OA treatment pathways tailored to these phenotypes where services such as pain coping skills training, relaxation training, and psychological therapies are delivered to patients who exhibit phenotypes characterized by high distress or negative pain coping. Future studies should evaluate whether tailoring treatment to specific psychological phenotypes yields better clinical outcomes than nontailored treatments, or treatments that have a more biomedical focus. Level of evidence: Level III, diagnostic study.

Clinical orthopaedics and related research · 79 citationsread the source →