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A Comprehensive Lifestyle Peer Group-Based Intervention on Cardiovascular Risk Factors: The Randomized Controlled Fifty-Fifty Program.

Background: Cardiovascular diseases stem from modifiable risk factors. Peer support is a proven strategy for many chronic illnesses. Randomized trials assessing the efficacy of this strategy for global cardiovascular risk factor modification are lacking. Objectives: This study assessed the hypothesis that a peer group strategy would help improve healthy behaviors in individuals with cardiovascular risk factors. Methods: A total of 543 adults 25 to 50 years of age with at least 1 risk factor were recruited; risk factors included hypertension (20%), overweight (82%), smoking (31%), and physical inactivity (81%). Subjects were randomized 1:1 to a peer group-based intervention group (IG) or a self-management control group (CG) for 12 months. Peer-elected leaders moderated monthly meetings involving role-play, brainstorming, and activities to address emotions, diet, and exercise. The primary outcome was mean change in a composite score related to blood pressure, exercise, weight, alimentation, and tobacco (Fuster-BEWAT score, 0 to 15). Multilevel models with municipality as a cluster variable were applied to assess differences between groups. Results: Participants' mean age was 42 ± 6 years, 71% were female, and they had a mean baseline Fuster-BEWAT score of 8.42 ± 2.35. After 1 year, the mean scores were significantly higher in the IG (n = 277) than in the CG (n = 266) (IG mean score: 8.84; 95% confidence interval (CI): 8.37 to 9.32; CG mean score: 8.17; 95% CI: 7.55 to 8.79; p = 0.02). The increase in the overall score was significantly larger in the IG compared with the CG (difference: 0.75; 95% CI: 0.32 to 1.18; p = 0.02). The mean improvement in the individual components was uniformly greater in the IG, with a significant difference for the tobacco component. Conclusions: The peer group intervention had beneficial effects on cardiovascular risk factors, with significant improvements in the overall score and specifically on tobacco cessation. A follow-up assessment will be performed 1 year after the final assessment reported here to determine long-term sustainability of the improvements associated with peer group intervention. (Peer-Group-Based Intervention Program [Fifty-Fifty]; NCT02367963).

Journal of the American College of Cardiology · randomised controlled trial · 79 citationsread the source →

5-year mental health and eating pattern outcomes following bariatric surgery in adolescents: a prospective cohort study.

Background: Mental health problems are prevalent among adolescents with severe obesity, but long-term mental health outcomes after adolescent bariatric surgery are not well known. We aimed to assess mental health outcomes over 5 years of follow-up after Roux-en-Y gastric bypass surgery in adolescents who participated in the Adolescent Morbid Obesity Surgery (AMOS) study. Methods: This was a non-randomised matched-control study in adolescents aged 13-18 years who had a BMI of 40 kg/m2 or higher, or 35 kg/m2 or higher in addition to obesity-related comorbidity; who had previously undergone failed comprehensive conservative treatment; and were of pubertal Tanner stage III or higher, with height growth velocity beyond peak. A contemporary control group, matched for BMI, age, and sex, who underwent conventional obesity treatment, was obtained from the Swedish Childhood Obesity Treatment Register. Data on dispensed psychiatric drugs and specialist treatment for mental disorders were retrieved from national registers with complete coverage. In the surgical group only, questionnaires were used to assess self-esteem (Rosenberg Self-Esteem [RSE] score), mood (Mood Adjective Checklist [MACL]), and eating patterns (Binge Eating Scale [BES] and Three-Factor Eating Questionnaire-R21 [TFEQ]). This study is registered with ClinicalTrials.gov (NCT00289705). Findings: Between April 10, 2006, and May 20, 2009, 81 adolescents (53 [65%] female) underwent Roux-en-Y gastric bypass surgery, and 80 control participants received conventional treatment. The proportion of participants prescribed psychiatric drugs did not differ between groups in the years before study inclusion (pre-baseline; absolute risk difference 5% [95% CI -7 to 16], p=0·4263) or after intervention (10% [-6 to 24], p=0·2175). Treatment for mental and behavioural disorders did not differ between groups before baseline (2% [-10 to 14], p=0·7135); however, adolescents in the surgical group had more specialised psychiatric treatment in the 5 years after obesity treatment than did the control group (15% [1 to 28], p=0·0410). There were few patients who discontinued psychiatric treatment post-surgery (three [4%] receiving psychiatric drug treatment and six [7%] receiving specialised care for a mental disorder before surgery). In the surgical group, self-esteem (RSE score) was improved after 5 years (mixed model mean 21·6 [95% CI 19·9 to 23·4]) relative to baseline (18·9 [17·4 to 20·4], p=0·0059), but overall mood (MACL score) was not (2·8 [2·7 to 2·9] at 5 years vs 2·7 [2·6 to 2·8] at baseline, p=0·0737). Binge eating was improved at 5 years (9·3 [7·4 to 11·2]) relative to baseline (15·0 [13·5 to 16·5], p<0·0001). Relative changes in BMI were not associated with the presence or absence of binge eating at baseline. Interpretation: Mental health problems persist in adolescents 5 years after bariatric surgery despite substantial weight loss. Although bariatric surgery can improve many aspects of health, alleviation of mental health problems should not be expected, and a multidisciplinary bariatric team should offer long-term mental health support after surgery. Funding: Swedish Research Council, VINNOVA, Västra Götalandsregionen, ALF VG-region, Region Stockholm, Swedish Child Diabetes Foundation, Swedish Heart and Lung Foundation, Tore Nilsson's Foundation, SUS Foundations and Donations, Capio Research Foundation, and Mary von Sydow's Foundation.

The Lancet. Child & adolescent health · 44 citationsread the source →

Music interventions for improving psychological and physical outcomes in people with cancer.

Background: This is an update of the review published on the Cochrane Library in 2016, Issue 8. Having cancer may result in extensive emotional, physical and social suffering. Music interventions have been used to alleviate symptoms and treatment side effects in people with cancer. This review includes music interventions defined as music therapy offered by trained music therapists, as well as music medicine, which was defined as listening to pre-recorded music offered by medical staff. Objectives: To assess and compare the effects of music therapy and music medicine interventions for psychological and physical outcomes in people with cancer. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 3) in the Cochrane Library, MEDLINE via Ovid, Embase via Ovid, CINAHL, PsycINFO, LILACS, Science Citation Index, CancerLit, CAIRSS, Proquest Digital Dissertations, ClinicalTrials.gov, Current Controlled Trials, the RILM Abstracts of Music Literature, http://www.wfmt.info/Musictherapyworld/ and the National Research Register. We searched all databases, except for the last two, from their inception to April 2020; the other two are no longer functional, so we searched them until their termination date. We handsearched music therapy journals, reviewed reference lists and contacted experts. There was no language restriction. Selection criteria: We included all randomized and quasi-randomized controlled trials of music interventions for improving psychological and physical outcomes in adults and pediatric patients with cancer. We excluded patients undergoing biopsy and aspiration for diagnostic purposes. Data collection and analysis: Two review authors independently extracted the data and assessed the risk of bias. Where possible, we presented results in meta-analyses using mean differences and standardized mean differences. We used post-test scores. In cases of significant baseline difference, we used change scores. We conducted separate meta-analyses for studies with adult participants and those with pediatric participants. Primary outcomes of interest included psychological outcomes and physical symptoms and secondary outcomes included physiological responses, physical functioning, anesthetic and analgesic intake, length of hospitalization, social and spiritual support, communication, and quality of life (QoL) . We used GRADE to assess the certainty of the evidence. Main results: We identified 29 new trials for inclusion in this update. In total, the evidence of this review rests on 81 trials with a total of 5576 participants. Of the 81 trials, 74 trials included adult (N = 5306) and seven trials included pediatric (N = 270) oncology patients. We categorized 38 trials as music therapy trials and 43 as music medicine trials. The interventions were compared to standard care. Psychological outcomes The results suggest that music interventions may have a large anxiety-reducing effect in adults with cancer, with a reported average anxiety reduction of 7.73 units (17 studies, 1381 participants; 95% confidence interval (CI) -10.02 to -5.44; very low-certainty evidence) on the Spielberger State Anxiety Inventory scale (range 20 to 80; lower values reflect lower anxiety). Results also suggested a moderately strong, positive impact of music interventions on depression in adults (12 studies, 1021 participants; standardized mean difference (SMD): -0.41, 95% CI -0.67 to -0.15; very low-certainty evidence). We found no support for an effect of music interventions on mood (SMD 0.47, 95% CI -0.02 to 0.97; 5 studies, 236 participants; very low-certainty evidence). Music interventions may increase hope in adults with cancer, with a reported average increase of 3.19 units (95% CI 0.12 to 6.25) on the Herth Hope Index (range 12 to 48; higher scores reflect greater hope), but this finding was based on only two studies (N = 53 participants; very low-certainty evidence). Physical outcomes We found a moderate pain-reducing effect of music interventions (SMD -0.67, 95% CI -1.07 to -0.26; 12 studies, 632 adult participants; very low-certainty evidence). In addition, music interventions had a small treatment effect on fatigue (SMD -0.28, 95% CI -0.46 to -0.10; 10 studies, 498 adult participants; low-certainty evidence). The results suggest a large effect of music interventions on adult participants' QoL, but the results were highly inconsistent across studies, and the pooled effect size was accompanied by a large confidence interval (SMD 0.88, 95% CI -0.31 to 2.08; 7 studies, 573 participants; evidence is very uncertain). Removal of studies that used improper randomization methods resulted in a moderate effect size that was less heterogeneous (SMD 0.47, 95% CI 0.06 to 0.88, P = 0.02, I2 = 56%). A small number of trials included pediatric oncology participants. The findings suggest that music interventions may reduce anxiety but this finding was based on only two studies (SMD -0.94, 95% CI -1.9 to 0.03; very low-certainty evidence). Due to the small number of studies, we could not draw conclusions regarding the effects of music interventions on mood, depression, QoL, fatigue or pain in pediatric participants with cancer. The majority of studies included in this review update presented a high risk of bias, and therefore the overall certainty of the evidence is low. For several outcomes (i.e. anxiety, depression, pain, fatigue, and QoL) the beneficial treatment effects were consistent across studies for music therapy interventions delivered by music therapists. In contrast, music medicine interventions resulted in inconsistent treatment effects across studies for these outcomes. Authors' conclusions: This systematic review indicates that music interventions compared to standard care may have beneficial effects on anxiety, depression, hope, pain, and fatigue in adults with cancer. The results of two trials suggest that music interventions may have a beneficial effect on anxiety in children with cancer. Too few trials with pediatric participants were included to draw conclusions about the treatment benefits of music for other outcomes. For several outcomes, music therapy interventions delivered by a trained music therapist led to consistent results across studies and this was not the case for music medicine interventions. Moreover, evidence of effect was found for music therapy interventions for QoL and fatigue but not for music medicine interventions. Most trials were at high risk of bias and low or very low certainty of evidence; therefore, these results need to be interpreted with caution.

The Cochrane database of systematic reviews · systematic review · 144 citationsread the source →

Social differences in breast cancer survival in relation to patient management within a National Health Care System (Sweden).

Epidemiologic studies have shown that cancer survival is poorer in low compared with high socioeconomic groups. We investigated whether these differences were associated with disparities in tumour characteristics and management. This cohort study was based on 9,908 women aged 20-79 years at diagnosis with primary breast cancer identified in a Swedish population-based clinical register. Information on socioeconomic standing was obtained from a social database. The 5-year cause-specific survival (CSS) and mortality hazard ratios (HR) were estimated by Cox proportional hazard models to assess differences in survival between socioeconomic groups while adjusting for diagnostic intensity, tumour characteristics and treatment. Following adjustment for age, year and stage at diagnosis, the risk of dying of breast cancer was 35% lower among women with high education compared with that of low education (HR = 0.65, 95% CI 0.53-0.80). When compared with women with high education, a lower percentage of women with low education had been investigated for proliferation (84 vs. 76%) or hormone receptor status (89 vs. 81%), had tumours <or=20 mm (68 vs. 64%), were treated at a main hospital (75 vs. 68%) and had received radiation treatment (80 vs. 67%) or chemotherapy (31 vs. 18%). However, these proportional differences could not explain the observed social gradient in survival. To minimize social differences in breast cancer survival, further research should address not only factors leading to inequities in management but also focus on patient factors such as health awareness, comorbidity burden and compliance to adjuvant treatment.

International journal of cancer · 56 citationsread the source →

Impaired survival and long-term neurological problems in benign meningioma.

Purpose: To assess long-term functional outcome and survival among patients with meningioma World Health Organization (WHO) grade I. Methods: Retrospective analysis of 205 patients after resection of WHO grade I intracranial meningioma from 1985 through 2003. Expected age- and sex-specific survival was calculated by applying Dutch life-table statistics to each patient for the individual duration of follow-up. Long-term functional outcome was assessed using a mailed questionnaire to the general practitioner. Results: The mean duration of follow-up was 11.5 years. Survival at 5, 10, 15, and 20 years was 92%, 81%, 63%, and 53%, respectively, which is significantly lower than the expected survival (94%, 86%, 78%, and 66%, respectively). Survival was worse with higher age (P < .001). Survival among patients younger than 45 years and older than 65 years was comparable to the expected survival but significantly worse among patients aged 45-65 years. Analysis of the cause of death suggests an excess mortality associated with both brain tumor death and stroke (P = .07). Recurrence rates at 5, 10, and 15 years were 18%, 26%, and 32%, respectively. Higher Simpson grade (P < .001) and lower age (P = .02) were associated with a higher recurrence rate. In 29 patients (14%) receiving radiotherapy, the 5-year recurrence rate was 18% and the 5-year survival was only 58%. Long-term functioning (≥ 5 years after last treatment) could be assessed in 89 long-term survivors: 29 patients (33%) showed no deficits, and 60 (67%) showed at least 1 neurological symptom, of whom 24 (27%) were unable to perform normal daily activities. Conclusion: Long-term survival in WHO grade I meningioma is challenged in patients more than 45 years of age. Excess mortality seems to be associated with both tumor recurrence and stroke. The majority of patients have long-term neurological problems.

Neuro-oncology · 165 citationsread the source →

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

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

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

Effectiveness of a brief behavioural intervention on psychological distress among women with a history of gender-based violence in urban Kenya: A randomised clinical trial.

Background: Gender-based violence (GBV) represents a major cause of psychological morbidity worldwide, and particularly in low- and middle-income countries (LMICs). Although there are effective treatments for common mental disorders associated with GBV, they typically require lengthy treatment programs that may limit scaling up in LMICs. The aim of this study was to test the effectiveness of a new 5-session behavioural treatment called Problem Management Plus (PM+) that lay community workers can be taught to deliver. Methods and findings: In this single-blind, parallel, randomised controlled trial, adult women who had experienced GBV were identified through community screening for psychological distress and impaired functioning in Nairobi, Kenya. Participants were randomly allocated in a 1:1 ratio either to PM+ delivered in the community by lay community health workers provided with 8 days of training or to facility-based enhanced usual care (EUC) provided by community nurses. Participants were aware of treatment allocation, but research assessors were blinded. The primary outcome was psychological distress as measured by the total score on the 12-item General Health Questionnaire (GHQ-12) assessed at 3 months after treatment. Secondary outcomes were impaired functioning (measured by the WHO Disability Adjustment Schedule [WHODAS]), symptoms of posttraumatic stress (measured by the Posttraumatic Stress Disorder Checklist [PCL]), personally identified problems (measured by Psychological Outcome Profiles [PSYCHLOPS]), stressful life events (measured by the Life Events Checklist [LEC]), and health service utilisation. Between 15 April 2015 and 20 August 2015, 1,393 women were screened for eligibility on the basis of psychological distress and impaired functioning. Of these, 518 women (37%) screened positive, of whom 421 (81%) were women who had experienced GBV. Of these 421 women, 209 were assigned to PM+ and 212 to EUC. Follow-up assessments were completed on 16 January 2016. The primary analysis was intention to treat and included 53 women in PM+ (25%) and 49 women in EUC (23%) lost to follow-up. The difference between PM+ and EUC in the change from baseline to 3 months on the GHQ-12 was 3.33 (95% CI 1.86-4.79, P = 0.001) in favour of PM+. In terms of secondary outcomes, for WHODAS the difference between PM+ and EUC in the change from baseline to 3-month follow-up was 1.96 (95% CI 0.21-3.71, P = 0.03), for PCL it was 3.95 (95% CI 0.06-7.83, P = 0.05), and for PSYCHLOPS it was 2.15 (95% CI 0.98-3.32, P = 0.001), all in favour of PM+. These estimated differences correspond to moderate effect sizes in favour of PM+ for GHQ-12 score (0.57, 95% CI 0.32-0.83) and PSYCHLOPS (0.67, 95% CI 0.31-1.03), and small effect sizes for WHODAS (0.26, 95% CI 0.02-0.50) and PCL (0.21, 95% CI 0.00-0.41). Twelve adverse events were reported, all of which were suicidal risks detected during screening. No adverse events were attributable to the interventions or the trial. Limitations of the study include no long-term follow-up, reliance on self-report rather than structured interview data, and lack of an attention control condition. Conclusions: Among a community sample of women in urban Kenya with a history of GBV, a brief, lay-administered behavioural intervention, compared with EUC, resulted in moderate reductions in psychological distress at 3-month follow-up. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12614001291673.

PLoS medicine · randomised controlled trial · 156 citationsread the source →

An internet-based intervention with brief nurse support to manage obesity in primary care (POWeR+): a pragmatic, parallel-group, randomised controlled trial.

Background: The obesity epidemic has major public health consequences. Expert dietetic and behavioural counselling with intensive follow-up is effective, but resource requirements severely restrict widespread implementation in primary care, where most patients are managed. We aimed to estimate the effectiveness and cost-effectiveness of an internet-based behavioural intervention (POWeR+) combined with brief practice nurse support in primary care. Methods: We did this pragmatic, parallel-group, randomised controlled trial at 56 primary care practices in central and south England. Eligible adults aged 18 years or older with a BMI of 30 kg/m(2) or more (or ≥28 kg/m(2) with hypertension, hypercholesterolaemia, or diabetes) registered online with POWeR+-a 24 session, web-based, weight management intervention lasting 6 months. After registration, the website automatically randomly assigned patients (1:1:1), via computer-generated random numbers, to receive evidence-based dietetic advice to swap foods for similar, but healthier, choices and increase fruit and vegetable intake, in addition to 6 monthly nurse follow-up (control group); web-based intervention and face-to-face nurse support (POWeR+Face-to-face [POWeR+F]; up to seven nurse contacts over 6 months); or web-based intervention and remote nurse support (POWeR+Remote [POWeR+R]; up to five emails or brief phone calls over 6 months). Participants and investigators were masked to group allocation at the point of randomisation; masking of participants was not possible after randomisation. The primary outcome was weight loss averaged over 12 months. We did a secondary analysis of weight to measure maintenance of 5% weight loss at months 6 and 12. We modelled the cost-effectiveness of each intervention. We did analysis by intention to treat, with multiple imputation for missing data. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN21244703. Findings: Between Jan 30, 2013, and March 20, 2014, 818 participants were randomly assigned to the control group (n=279), the POWeR+F group (n=269), or the POWeR+R group (n=270). Weight loss averaged over 12 months was recorded in 666 (81%) participants. The control group lost almost 3 kg over 12 months (crude mean weight: baseline 104·38 kg [SD 21·11; n=279], 6 months 101·91 kg [19·35; n=136], 12 months 101·74 kg [19·57; n=227]). The primary imputed analysis showed that compared with the control group, patients in the POWeR+F group achieved an additional weight reduction of 1·5 kg (95% CI 0·6-2·4; p=0·001) averaged over 12 months, and patients in the POWeR+R group achieved an additional 1·3 kg (0·34-2·2; p=0·007). 21% of patients in the control group had maintained a clinically important 5% weight reduction at month 12, compared with 29% of patients in the POWeR+F group (risk ratio 1·56, 0·96-2·51; p=0·070) and 32% of patients in the POWeR+R group (1·82, 1·31-2·74; p=0·004). The incremental overall cost to the health service per kg weight lost with the POWeR+ interventions versus the control strategy was £18 (95% CI -129 to 195) for POWeR+F and -£25 (-268 to 157) for POWeR+R; the probability of being cost-effective at a threshold of £100 per kg lost was 88% and 98%, respectively. No adverse events were reported. Interpretation: Weight loss can be maintained in some individuals by use of novel written material with occasional brief nurse follow-up. However, more people can maintain clinically important weight reductions with a web-based behavioural program and brief remote follow-up, with no increase in health service costs. Future research should assess the extent to which clinically important weight loss can be maintained beyond 1 year. Funding: Health Technology Assessment Programme of the National Institute for Health Research.

The lancet. Diabetes & endocrinology · randomised controlled trial · 85 citationsread the source →

3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial.

Background: Post-traumatic stress disorder (PTSD) is prevalent in military personnel and first responders, many of whom do not respond to currently available treatments. This study aimed to assess the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for treating chronic PTSD in this population. Methods: We did a randomised, double-blind, dose-response, phase 2 trial at an outpatient psychiatric clinic in the USA. We included service personnel who were 18 years or older, with chronic PTSD duration of 6 months or more, and who had a Clinician-Administered PTSD Scale (CAPS-IV) total score of 50 or greater. Using a web-based randomisation system, we randomly assigned participants (1:1:2) to three different dose groups of MDMA plus psychotherapy: 30 mg (active control), 75 mg, or 125 mg. We masked investigators, independent outcome raters, and participants until after the primary endpoint. MDMA was administered orally in two 8-h sessions with concomitant manualised psychotherapy. The primary outcome was mean change in CAPS-IV total score from baseline to 1 month after the second experimental session. Participants in the 30 mg and 75 mg groups subsequently underwent three 100-125 mg MDMA-assisted psychotherapy sessions in an open-label crossover, and all participants were assessed 12 months after the last MDMA session. Safety was monitored through adverse events, spontaneously reported expected reactions, vital signs, and suicidal ideation and behaviour. This study is registered with ClinicalTrials.gov, number NCT01211405. Findings: Between Nov 10, 2010, and Jan 29, 2015, 26 veterans and first responders met eligibility criteria and were randomly assigned to receive 30 mg (n=7), 75 mg (n=7), or 125 mg (n=12) of MDMA plus psychotherapy. At the primary endpoint, the 75 mg and 125 mg groups had significantly greater decreases in PTSD symptom severity (mean change CAPS-IV total scores of -58·3 [SD 9·8] and -44·3 [28·7]; p=0·001) than the 30 mg group (-11·4 [12·7]). Compared with the 30 mg group, Cohen's d effect sizes were large: 2·8 (95% CI 1·19-4·39) for the 75 mg group and 1·1 (0·04-2·08) for the 125 mg group. In the open-label crossover with full-dose MDMA (100-125 mg), PTSD symptom severity significantly decreased in the group that had previously received 30 mg (p=0·01), whereas no further significant decreases were observed in the group that previously achieved a large response after 75 mg doses in the blinded segment (p=0·81). PTSD symptoms were significantly reduced at the 12-month follow-up compared with baseline after all groups had full-dose MDMA (mean CAPS-IV total score of 38·8 [SD 28·1] vs 87·1 [16·1]; p<0·0001). 85 adverse events were reported by 20 participants. Of these adverse events, four (5%) were serious: three were deemed unrelated and one possibly related to study drug treatment. Interpretation: Active doses (75 mg and 125 mg) of MDMA with adjunctive psychotherapy in a controlled setting were effective and well tolerated in reducing PTSD symptoms in veterans and first responders. Funding: Multidisciplinary Association for Psychedelic Studies.

The lancet. Psychiatry · randomised controlled trial · 258 citationsread the source →

Randomised controlled trial and economic analysis of an internet-based weight management programme: POWeR+ (Positive Online Weight Reduction).

Background: Behavioural counselling with intensive follow-up for obesity is effective, but in resource-constrained primary care settings briefer approaches are needed. Objectives: To estimate the clinical effectiveness and cost-effectiveness of an internet-based behavioural intervention with regular face-to-face or remote support in primary care, compared with brief advice. Design: Individually randomised three-arm parallel trial with health economic evaluation and nested qualitative interviews. Setting: Primary care general practices in the UK. Participants: Patients with a body mass index of ≥ 30 kg/m2 (or ≥ 28 kg/m2 with risk factors) identified from general practice records, recruited by postal invitation. Interventions: Positive Online Weight Reduction (POWeR+) is a 24-session, web-based weight management intervention completed over 6 months. Following online registration, the website randomly allocated participants using computer-generated random numbers to (1) the control intervention (n = 279), which had previously been demonstrated to be clinically effective (brief web-based information that minimised pressure to cut down foods, instead encouraging swaps to healthier choices and increasing fruit and vegetables, plus 6-monthly nurse weighing); (2) POWeR+F (n = 269), POWeR+ supplemented by face-to-face nurse support (up to seven contacts); or (3) POWeR+R (n = 270), POWeR+ supplemented by remote nurse support (up to five e-mails or brief telephone calls). Main outcome measures: The primary outcome was a modelled estimate of average weight reduction over 12 months, assessed blind to group where possible, using multiple imputation for missing data. The secondary outcome was the number of participants maintaining a 5% weight reduction at 12 months. Results: A total of 818 eligible individuals were randomised using computer-generated random numbers. Weight change, averaged over 12 months, was documented in 666 out of 818 participants (81%; control, n = 227; POWeR+F, n = 221; POWeR+R, n = 218). The control group maintained nearly 3 kg of weight loss per person (mean weight per person: baseline, 104.4 kg; 6 months, 101.9 kg; 12 months, 101.7 kg). Compared with the control group, the estimated additional weight reduction with POWeR+F was 1.5 kg [95% confidence interval (CI) 0.6 to 2.4 kg; p = 0.001] and with POWeR+R was 1.3 kg (95% CI 0.34 to 2.2 kg; p = 0.007). By 12 months the mean weight loss was not statistically significantly different between groups, but 20.8% of control participants, 29.2% of POWeR+F participants (risk ratio 1.56, 95% CI 0.96 to 2.51; p = 0.070) and 32.4% of POWeR+R participants (risk ratio 1.82, 95% CI 1.31 to 2.74; p = 0.004) maintained a clinically significant 5% weight reduction. The POWeR+R group had fewer individuals who reported doing another activity to help lose weight [control, 47.1% (64/136); POWeR+F, 37.2% (51/137); POWeR+R, 26.7% (40/150)]. The incremental cost to the health service per kilogram weight lost, compared with the control group, was £18 (95% CI -£129 to £195) for POWeR+F and -£25 (95% CI -£268 to £157) for POWeR+R. The probability of being cost-effective at a threshold of £100 per kilogram was 88% and 98% for POWeR+F and POWeR+R, respectively. POWeR+R was dominant compared with the control group. No harms were reported and participants using POWeR+ felt more enabled in managing their weight. The qualitative studies documented that POWeR+ was viewed positively by patients and that health-care professionals generally enjoyed supporting patients using POWeR+. Study limitations: Maintenance of weight loss after 1 year is unknown. Future work: Identifying strategies for longer-term engagement, impact in community settings and increasing physical activity. Conclusion: Clinically valuable weight loss (> 5%) is maintained in 20% of individuals using novel written materials with brief follow-up. A web-based behavioural programme and brief support results in greater mean weight loss and 10% more participants maintain valuable weight loss; it achieves greater enablement and fewer participants undertaking other weight-loss activities; and it is likely to be cost-effective. Trial registration: Current Controlled Trials ISRCTN21244703. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 4. See the NIHR Journals Library website for further project information.

Health technology assessment (Winchester, England) · randomised controlled trial · 34 citationsread the source →

Surgical management of pelvic organ prolapse in women.

Background: Pelvic organ prolapse may occur in up to 50% of parous women. A variety of urinary, bowel and sexual symptoms may be associated with the prolapse. Objectives: To determine the effects of the many different surgeries used in the management of pelvic organ prolapse. Search methods: We searched the Cochrane Incontinence Group Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In Process and handsearching of journals and conference proceedings, healthcare-related bibliographic databases, handsearched conference proceedings (searched 20 August 2012), and reference lists of relevant articles. We also contacted researchers in the field. Selection criteria: Randomised or quasi-randomised controlled trials that included surgical operations for pelvic organ prolapse. Data collection and analysis: Trials were assessed and data extracted independently by two review authors. Six investigators were contacted for additional information with five responding. Main results: Fifty-six randomised controlled trials were identified evaluating 5954 women. For upper vaginal prolapse (uterine or vault) abdominal sacral colpopexy was associated with a lower rate of recurrent vault prolapse on examination and painful intercourse than with vaginal sacrospinous colpopexy. These benefits must be balanced against a longer operating time, longer time to return to activities of daily living and increased cost of the abdominal approach. In single studies the sacral colpopexy had a higher success rate on examination and lower reoperation rate than high vaginal uterosacral suspension and transvaginal polypropylene mesh. Twenty-one trials compared a variety of surgical procedures for anterior compartment prolapse (cystocele). Ten compared native tissue repair with graft (absorbable and permanent mesh, biological grafts) repair for anterior compartment prolapse. Native tissue anterior repair was associated with more recurrent anterior compartment prolapse than when supplemented with a polyglactin (absorbable) mesh inlay (RR 1.39, 95% CI 1.02 to 1.90) or porcine dermis mesh inlay (RR 2.08, 95% CI 1.08 to 4.01), however there was no difference in post-operative awareness of prolapse after absorbable mesh (RR 0.96, 95% CI 0.33 to 2.81) or a biological graft (RR 1.21, 95% CI 0.64 to 2.30). Data on morbidity and other clinical outcomes were lacking. Standard anterior repair was associated with more anterior compartment prolapse on examination than for any polypropylene (permanent) mesh repair (RR 3.15, 95% CI 2.50 to 3.96). Awareness of prolapse was also higher after the anterior repair as compared to polypropylene mesh repair (28% versus 18%, RR 1.57, 95% CI 1.18 to 2.07). However, the reoperation rate for prolapse was similar at 14/459 (3%) after the native tissue repair compared to 6/470 (1.3%) (RR 2.18, 95% CI 0.93 to 5.10) after the anterior polypropylene mesh repair and no differences in quality of life data or de novo dyspareunia were identified. Blood loss (MD 64 ml, 95% CI 48 to 81), operating time (MD 19 min, 95% CI 16 to 21), recurrences in apical or posterior compartment (RR 1.9, 95% CI 1.0 to 3.4) and de novo stress urinary incontinence (RR 1.8, 95% CI 1.0 to 3.1) were significantly higher with transobturator meshes than for native tissue anterior repair. Mesh erosions were reported in 11.4% (64/563), with surgical interventions being performed in 6.8% (32/470).Data from three trials compared native tissue repairs with a variety of total, anterior, or posterior polypropylene kit meshes for vaginal prolapse in multiple compartments. While no difference in awareness of prolapse was able to be identified between the groups (RR 1.3, 95% CI 0.6 to 1.7) the recurrence rate on examination was higher in the native tissue repair group compared to the transvaginal polypropylene mesh group (RR 2.0, 95% CI 1.3 to 3.1). The mesh erosion rate was 35/194 (18%), and 18/194 (9%) underwent surgical correction for mesh erosion. The reoperation rate after transvaginal polypropylene mesh repair of 22/194 (11%) was higher than after the native tissue repair (7/189, 3.7%) (RR 3.1, 95% CI 1.3 to 7.3).Data from three trials compared posterior vaginal repair and transanal repair for the treatment of posterior compartment prolapse (rectocele). The posterior vaginal repair had fewer recurrent prolapse symptoms (RR 0.4, 95% CI 0.2 to 1.0) and lower recurrence on examination (RR 0.2, 95% CI 0.1 to 0.6) and on defecography (MD -1.2 cm, 95% CI -2.0 to -0.3).Sixteen trials included significant data on bladder outcomes following a variety of prolapse surgeries. Women undergoing prolapse surgery may have benefited from having continence surgery performed concomitantly, especially if they had stress urinary incontinence (RR 7.4, 95% CI 4.0 to 14) or if they were continent and had occult stress urinary incontinence demonstrated pre-operatively (RR 3.5, 95% CI 1.9 to 6.6). Following prolapse surgery, 12% of women developed de novo symptoms of bladder overactivity and 9% de novo voiding dysfunction. Authors' conclusions: Sacral colpopexy has superior outcomes to a variety of vaginal procedures including sacrospinous colpopexy, uterosacral colpopexy and transvaginal mesh. These benefits must be balanced against a longer operating time, longer time to return to activities of daily living, and increased cost of the abdominal approach. The use of mesh or graft inlays at the time of anterior vaginal wall repair reduces the risk of recurrent anterior wall prolapse on examination. Anterior vaginal polypropylene mesh also reduces awareness of prolapse, however these benefits must be weighted against increased operating time, blood loss, rate of apical or posterior compartment prolapse, de novo stress urinary incontinence, and reoperation rate for mesh exposures associated with the use of polypropylene mesh. Posterior vaginal wall repair may be better than transanal repair in the management of rectocele in terms of recurrence of prolapse. The evidence is not supportive of any grafts at the time of posterior vaginal repair. Adequately powered randomised, controlled clinical trials with blinding of assessors are urgently needed on a wide variety of issues, and they particularly need to include women's perceptions of prolapse symptoms. Following the withdrawal of some commercial transvaginal mesh kits from the market, the generalisability of the findings, especially relating to anterior compartment transvaginal mesh, should be interpreted with caution.

The Cochrane database of systematic reviews · meta-analysis · 393 citationsread the source →

Direct Parabrachial-Cortical Connectivity.

The parabrachial nucleus (PB) in the upper brain stem tegmentum includes several neuronal subpopulations with a wide variety of connections and functions. A subpopulation of PB neurons projects axons directly to the cerebral cortex, and limbic areas of the cerebral cortex send a return projection directly to the PB. We used retrograde and Cre-dependent anterograde tracing to identify genetic markers and characterize this PB-cortical interconnectivity in mice. Cortical projections originate from glutamatergic PB neurons that contain Lmx1b (81%), estrogen receptor alpha (26%), and Satb2 (20%), plus mRNA for the neuropeptides cholecystokinin (Cck, 48%) and calcitonin gene-related peptide (Calca, 13%), with minimal contribution from FoxP2+ PB neurons (2%). Axons from the PB produce an extensive terminal field in an unmyelinated region of the insular cortex, extending caudally into the entorhinal cortex, and arcing rostrally through the dorsolateral prefrontal cortex, with a secondary terminal field in the medial prefrontal cortex. In return, layer 5 neurons in the insular cortex and other prefrontal areas, along with a dense cluster of cells dorsal to the claustrum, send a descending projection to subregions of the PB that contain cortically projecting neurons. This information forms the neuroanatomical basis for testing PB-cortical interconnectivity in arousal and interoception.

Cerebral cortex (New York, N.Y. : 1991) · 55 citationsread the source →

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

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

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

Skills to Enhance Positivity in Suicidal Adolescents: Results From an Open Development Trial.

"Skills to Enhance Positivity" (STEP) is a two-part positive affect program designed to decrease recurrent suicidal behavior in adolescents hospitalized due to suicide risk. Here, we describe the initial pilot phase in which the intervention was developed and modified based on a sample of 20 adolescent participants, aged 12 to 18 years old ( Mage = 15.9, SD = 1.5). STEP consisted of an in-person phase (four sessions) and a remote delivery phase (text messaging and phone calls). The inpatient sessions focused on psychoeducation of positive affect, mindfulness meditation, gratitude, and savoring. The remote delivery phase comprised of weekly phone calls and daily text messages to enhance mood monitoring and skills practice reminders. Average session attendance was 81%, and mean daily response rate to text messages was 73.6%, demonstrating high engagement. STEP was described as good or excellent by over 90% of parents and 100% of adolescents. Only one participant had a suicide attempt, and five were readmitted for suicidality in the following 6 months, fewer than comparable naturalistic studies. Although preliminary results are promising, larger randomized trials are needed to determine the efficacy of STEP in reducing suicidal behaviors.

Behavior modification · clinical trial · 15 citationsread the source →

Video decision support tool for advance care planning in dementia: randomised controlled trial.

Objective: To evaluate the effect of a video decision support tool on the preferences for future medical care in older people if they develop advanced dementia, and the stability of those preferences after six weeks. Design: Randomised controlled trial conducted between 1 September 2007 and 30 May 2008. Setting Four primary care clinics (two geriatric and two adult medicine) affiliated with three academic medical centres in Boston. Participants: Convenience sample of 200 older people (>or=65 years) living in the community with previously scheduled appointments at one of the clinics. Mean age was 75 and 58% were women. Intervention: Verbal narrative alone (n=106) or with a video decision support tool (n=94). Main outcome measures: Preferred goal of care: life prolonging care (cardiopulmonary resuscitation, mechanical ventilation), limited care (admission to hospital, antibiotics, but not cardiopulmonary resuscitation), or comfort care (treatment only to relieve symptoms). Preferences after six weeks. The principal category for analysis was the difference in proportions of participants in each group who preferred comfort care. Results: Among participants receiving the verbal narrative alone, 68 (64%) chose comfort care, 20 (19%) chose limited care, 15 (14%) chose life prolonging care, and three (3%) were uncertain. In the video group, 81 (86%) chose comfort care, eight (9%) chose limited care, four (4%) chose life prolonging care, and one (1%) was uncertain (chi(2)=13.0, df=3, P=0.003). Among all participants the factors associated with a greater likelihood of opting for comfort care were being a college graduate or higher, good or better health status, greater health literacy, white race, and randomisation to the video arm. In multivariable analysis, participants in the video group were more likely to prefer comfort care than those in the verbal group (adjusted odds ratio 3.9, 95% confidence interval 1.8 to 8.6). Participants were re-interviewed after six weeks. Among the 94/106 (89%) participants re-interviewed in the verbal group, 27 (29%) changed their preferences (kappa=0.35). Among the 84/94 (89%) participants re-interviewed in the video group, five (6%) changed their preferences (kappa=0.79) (P<0.001 for difference). Conclusion: Older people who view a video depiction of a patient with advanced dementia after hearing a verbal description of the condition are more likely to opt for comfort as their goal of care compared with those who solely listen to a verbal description. They also have more stable preferences over time. Trial registration: Clinicaltrials.gov NCT00704886.

BMJ (Clinical research ed.) · randomised controlled trial · 207 citationsread the source →

A pragmatic randomized controlled trial of computerized CBT (SPARX) for symptoms of depression among adolescents excluded from mainstream education.

Background: Adolescents excluded from mainstream education have high mental health needs. The use of computerized Cognitive Behavioural Therapy (cCBT) has not been investigated with this group. Aims: To test the efficacy of the SPARX cCBT programme for symptoms of depression among adolescents in programmes for students excluded or alienated from mainstream education. Method: Adolescents (32; 34% Maori, 38% Pacific Island, 56% male) aged 13-16 with Child Depression Rating Scale Revised (CDRS-R) scores indicating possible through to almost certain depressive disorder were randomized to SPARX to be completed over the following 5 weeks (n = 20) or to waitlist control (n = 12). Assessments were at baseline, 5 weeks and 10 weeks. Those in the wait condition were invited to complete SPARX after the 5 week assessment. Results: Most participants (n = 26, 81%) completed at least 4 levels of SPARX and 22 (69%) completed all 7 levels. Among the 30 (94%) participants who began treatment as randomized and provided 5-week data, significant differences were found between cCBT and wait groups on the CDRS-R (baseline to 5-week mean change -14.7 versus -1.1, p<.001), remission (78% vs. 36%, p = .047) and on the Reynolds Adolescent Depression Scale (-4.6 vs. +3.2 p = .05) but not on other self-rating psychological functioning scales. In intent-to-treat analyses CDRS-R changes and remission remained significant. Gains were maintained at 10-week follow-up. Conclusions: SPARX appears to be a promising treatment for students with symptoms of depression who are in alternative schooling programmes for those excluded from mainstream education.

Behavioural and cognitive psychotherapy · randomised controlled trial · 118 citationsread the source →

Comparison of therapeutic effects of omega-3 fatty acid eicosapentaenoic acid and fluoxetine, separately and in combination, in major depressive disorder.

Objective: To compare therapeutic effects of eicosapentaenoic acid (EPA), fluoxetine and a combination of them in major depression. Method: Sixty outpatients with a diagnosis of major depressive disorder based on DSM-IV criteria and a score >or=15 in the 17-item Hamilton Depression Rating Scale (HDRS) were randomly allocated to receive daily either 1000 mg EPA or 20 mg fluoxetine, or their combination for 8 weeks. Double dummy technique was used to double blind the study. Patients were assessed at 2 week intervals. Change in HDRS was the primary outcome measure. Results: Analysis of covariance for HDRS at week 8 across treatment groups was performed in 48 patients who completed at least 4 weeks of the study, with the last observation carried forward. Treatment, age of onset and baseline HDRS had a significant effect on HDRS at week 8. EPA + fluoxetine combination was significantly better than fluoxetine or EPA alone from the fourth week of treatment. Fluoxetine and EPA appear to be equally effective in controlling depressive symptoms. Response rates (>or=50% decrease in baseline HDRS) were 50%, 56% and 81% in the fluoxetine, EPA and combination groups, respectively. Conclusions: In the present 8 week trial EPA and fluoxetine had equal therapeutic effects in major depressive disorder. EPA + fluoxetine combination was superior to either of them alone.

The Australian and New Zealand journal of psychiatry · randomised controlled trial · 142 citationsread the source →

Screening and brief intervention for drug use in primary care: the ASPIRE randomized clinical trial.

Importance: The United States has invested substantially in screening and brief intervention for illicit drug use and prescription drug misuse, based in part on evidence of efficacy for unhealthy alcohol use. However, it is not a recommended universal preventive service in primary care because of lack of evidence of efficacy. Objective: To test the efficacy of 2 brief counseling interventions for unhealthy drug use (any illicit drug use or prescription drug misuse)-a brief negotiated interview (BNI) and an adaptation of motivational interviewing (MOTIV)-compared with no brief intervention. Design, setting, and participants: This 3-group randomized trial took place at an urban hospital-based primary care internal medicine practice; 528 adult primary care patients with drug use (Alcohol, Smoking, and Substance Involvement Screening Test [ASSIST] substance-specific scores of ≥4) were identified by screening between June 2009 and January 2012 in Boston, Massachusetts. Interventions: Two interventions were tested: the BNI is a 10- to 15-minute structured interview conducted by health educators; the MOTIV is a 30- to 45-minute intervention based on motivational interviewing with a 20- to 30-minute booster conducted by master's-level counselors. All study participants received a written list of substance use disorder treatment and mutual help resources. Main outcomes and measures: Primary outcome was number of days of use in the past 30 days of the self-identified main drug as determined by a validated calendar method at 6 months. Secondary outcomes included other self-reported measures of drug use, drug use according to hair testing, ASSIST scores (severity), drug use consequences, unsafe sex, mutual help meeting attendance, and health care utilization. Results: At baseline, 63% of participants reported their main drug was marijuana, 19% cocaine, and 17% opioids. At 6 months, 98% completed follow-up. Mean adjusted number of days using the main drug at 6 months was 12 for no brief intervention vs 11 for the BNI group (incidence rate ratio [IRR], 0.97; 95% CI, 0.77-1.22) and 12 for the MOTIV group (IRR, 1.05; 95% CI, 0.84-1.32; P = .81 for both comparisons vs no brief intervention). There were also no significant effects of BNI or MOTIV on any other outcome or in analyses stratified by main drug or drug use severity. Conclusions and relevance: Brief intervention did not have efficacy for decreasing unhealthy drug use in primary care patients identified by screening. These results do not support widespread implementation of illicit drug use and prescription drug misuse screening and brief intervention. Trial registration: clinicaltrials.gov Identifier: NCT00876941.

JAMA · randomised controlled trial · 225 citationsread the source →

The acute efficacy of antipsychotics in schizophrenia: a review of recent meta-analyses.

Schizophrenia is the eighth leading cause of disability worldwide in people aged 15-44 years. Before antidopaminergic antipsychotics were introduced in the 1950s, no effective medications existed for the treatment of schizophrenia. This review summarizes key meta-analytic findings regarding antipsychotic efficacy in the acute treatment of schizophrenia, including clozapine in treatment-resistant patients. In the most comprehensive meta-analysis of randomized controlled trials conducted in multi-episode schizophrenia, antipsychotics outperformed placebo regarding total symptoms, positive symptoms, negative symptoms, depressive symptoms, quality of life and social functioning. Amongst these outcomes, the standardized mean difference for overall symptoms was largest, that is, 0.47 (95% credible interval = 0.42-0.51), approaching a medium effect size, being reduced to 0.38 when publication bias and small-trial effects were accounted for. A comparison of two meta-analyses indicated that first-episode patients, compared with multi-episode patients, were more likely to have at least minimal treatment response [⩾20% Positive and Negative Syndrome Scale (PANSS)/Brief Psychiatric Rating Scale (BPRS) score reduction: 81% versus 51%] and good response (⩾50% PANSS/BPRS score reduction: 52% versus 23%). In multi-episode schizophrenia, no response or worsening after 2 weeks of a therapeutic antipsychotic dose was highly predictive of not achieving a good response at endpoint (median treatment = 6 weeks: specificity = 86%; positive predictive value = 90%), suggesting a change in treatment should be considered in such cases. In first-episode psychosis, adequately dosed antipsychotic treatment trials for more than 2 weeks are recommended before using no response or worsening as a decision point for aborting a given antipsychotic. In clearly defined treatment-resistant schizophrenia, clozapine generally outperformed other antipsychotics, especially when dosed appropriately (target = 3-6 months' duration; trough clozapine level ⩾350-400 μg/L) with a response rate (⩾20% PANSS/BPRS) of 33% by 3 months of treatment. High antipsychotic doses and psychotropic combinations are unlikely to be superior to standard doses of antipsychotic monotherapy. Acute antipsychotic efficacy in schizophrenia depends on the targeted symptom domain (greater efficacy: total and positive symptoms, lesser efficacy: negative symptoms, depressive symptoms, social functioning and quality of life). Greater antipsychotic efficacy is associated with higher total baseline symptom severity, treatment-naïveté/first-episode status, shorter illness duration, and trials that are nonindustry sponsored and that have a lower placebo effect. The heterogeneity of antipsychotic response across individuals and key symptom domains, the considerable degree of nonresponse/treatment resistance in multi-episode patients, and the adverse effect potential of antipsychotics are major limitations, underscoring the need to develop new medications for the treatment of schizophrenia. Drug development should include matching patient subgroups, which are identified by means of clinical and biomarker variables, to mechanisms of action of novel medications, targeting specific symptom domains, and investigating mechanisms of action other than dopaminergic blockade.

Therapeutic advances in psychopharmacology · review · 154 citationsread the source →

Visual outcome in infants born to drug-misusing mothers prescribed methadone in pregnancy.

Background: Flash visual evoked potentials (VEPs) were abnormal in a cohort of 100 neonates exposed to maintenance methadone in utero. This prospective cohort study now describes clinical visual and electrophysiological outcomes at 6 months. Methods: Visual assessment included modified Atkinson test battery; strabismus, nystagmus, reduced visual acuity, delayed visual maturation or refractive error (>3 dioptres) defined a fail. Pattern-onset VEPs were recorded to 120', 60' and 15' checks. Results: 81 drug-exposed and 26 comparison infants (79% and 52% of the original cohorts) were assessed at a median age of 27 weeks (range 26-30). 90% of drug-exposed infants had been additionally exposed to illicit drugs and 41% to excess alcohol in utero. 40% of the drug-exposed cohort failed clinical visual assessment: the relative risk of abnormal assessment was 5.1 (95% CI 1.3 to 20; p=0.02). Nystagmus was particularly common. VEP peak times were slower and amplitudes smaller in drug-exposed infants, of whom 70% had one or more abnormal VEP parameter. Abnormal visual outcome at 6 months was not associated with the pattern of additional drug exposure or a history of neonatal abstinence. Conclusions: Abnormal visual electrophysiology in infants born to drug-misusing mothers prescribed maintenance methadone persists to 6 months of age, and is associated with abnormal clinical visual assessment.

The British journal of ophthalmology · cohort or longitudinal · 53 citationsread the source →

Improving newborn preventive services at the birth hospitalization: a collaborative, hospital-based quality-improvement project.

Objective: The goal was to test the effectiveness of a statewide, collaborative, hospital-based quality-improvement project targeting preventive services delivered to healthy newborns during the birth hospitalization. Methods: All Vermont hospitals with obstetric services participated. The quality-improvement collaborative (intervention) was based on the Breakthrough Series Collaborative model. Targeted preventive services included hepatitis B immunization; assessment of breastfeeding; assessment of risk of hyperbilirubinemia; performance of metabolic and hearing screens; assessment of and counseling on tobacco smoke exposure, infant sleep position, car safety seat fit, and exposure to domestic violence; and planning for outpatient follow-up care. The effect of the intervention was assessed at the end of an 18-month period. Preintervention and postintervention chart audits were conducted by using a random sample of 30 newborn medical charts per audit for each participating hospital. Results: Documented rates of assessment improved for breastfeeding adequacy (49% vs 81%), risk for hyperbilirubinemia (14% vs 23%), infant sleep position (13% vs 56%), and car safety seat fit (42% vs 71%). Documented rates of counseling improved for tobacco smoke exposure (23% vs 53%) and car safety seat fit (38% vs 75%). Performance of hearing screens also improved (74% vs 97%). No significant changes were noted in performance of hepatitis B immunization (45% vs 30%) or metabolic screens (98% vs 98%), assessment of tobacco smoke exposure (53% vs 67%), counseling on sleep position (46% vs 68%), assessment of exposure to domestic violence (27% vs 36%), or planning for outpatient follow-up care (80% vs 71%). All hospitals demonstrated preintervention versus postintervention improvement of > or = 20% in > or = 1 newborn preventive service. Conclusions: A statewide, hospital-based quality-improvement project targeting hospital staff members and community physicians was effective in improving documented newborn preventive services during the birth hospitalization.

Pediatrics · cohort or longitudinal · 30 citationsread the source →

Scoping review of interventions aimed at promoting healthy screen use among adolescents.

Objectives: The objective of this scoping review is to map and synthesise existing literature on interventions aimed at promoting healthy screen use among adolescents. This review identifies the types, functions and settings of interventions, explores the diversity of targeted outcomes and highlights equity considerations and research gaps. Design: We conducted a scoping review in accordance with the Arksey and O'Malley framework and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines. Data sources: We systematically searched Medline, PsycINFO and ERIC from January 2013 to June 2024. Reference lists of included studies were also manually screened. Eligibility criteria: We included peer-reviewed experimental, quasi-experimental, observational and qualitative studies reporting on interventions designed to promote healthy screen use among adolescents aged 10-19 years. Data extraction and synthesis: One author extracted data using a structured charting form, and a second author verified all entries. Results were synthesised descriptively across key themes including target populations, theoretical frameworks, intervention components and reported outcomes. Results: From 6433 records, we identified 93 articles on 81 interventions, mainly conducted in high school settings in the USA and Australia. Most examined short-term interventions targeting recreational screen time. Outcomes included media literacy, cyberbullying, internet and gaming addiction, safe internet use, social media use and mental and sexual health. Seventy-eight per cent of interventions attempted to educate adolescents, while 34% offered training activities (eg, educational sessions to elevate risk awareness and skill-based training to enhance digital literacy and self-regulation). Interventions targeting external influences were used less frequently. About 20% of studies showed no statistically significant findings, highlighting the need to promote evidence-based interventions. Conclusion: This review identifies a need for broader, multilevel strategies that account for contextual factors and social determinants in influencing screen use and its related health issues. Future research should explore long-term effectiveness while examining the potential moderating and mediating effects of social determinants. Equity considerations were not a primary focus of most interventions, underscoring an important gap in this literature. Future interventions could incorporate equity-focused design and evaluation to ensure they respond to the needs of diverse adolescent populations.

BMJ open · review · 1 citationsread the source →

How Do Corticosteroids Work in Asthma?

Reviews2 September 2003How Do Corticosteroids Work in Asthma?Peter J. Barnes, DM, DSc and Ian M. Adcock, PhDPeter J. Barnes, DM, DScFrom National Heart and Lung Institute, Imperial College, London, United Kingdom. Search for more papers by this author and Ian M. Adcock, PhDFrom National Heart and Lung Institute, Imperial College, London, United Kingdom. Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-139-5_Part_1-200309020-00012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Clinical PrinciplesAsthma is the most common chronic disease in westernized countries. Patients with asthma have an underlying chronic inflammation of the airways characterized by activated mast cells, eosinophils, and T-helper 2 lymphocytes. This results in increased responsiveness of the airways to such triggers as exercise, allergens, and air pollutants. This chronic inflammation underlies the typical symptoms of asthma, which include intermittent wheezing, coughing, shortness of breath, and chest tightness. Corticosteroids are the most effective treatment for asthma, and inhaled corticosteroids have become first-line treatment for children and adults with persistent symptoms. Corticosteroids suppress the chronic airway inflammation in patients with asthma, and the molecular ...References1. Busse WW, Lemanske RF. Asthma. N Engl J Med. 2001;344:350-62. [PMID: 11172168] CrossrefMedlineGoogle Scholar2. Barnes PJ, Chung KF, Page CP. Inflammatory mediators of asthma: an update. Pharmacol Rev. 1998;50:515-96. [PMID: 9860804] MedlineGoogle Scholar3. Barnes PJ, Adcock IM. Transcription factors and asthma. Eur Respir J. 1998;12:221-34. [PMID: 9701442] CrossrefMedlineGoogle Scholar4. Hart LA, Krishnan VL, Adcock IM, Barnes PJ, Chung KF. Activation and localization of transcription factor, nuclear factor-B, in asthma. Am J Respir Crit Care Med. 1998;158:1585-92. [PMID: 9817712] CrossrefMedlineGoogle Scholar5. Barnes PJ, Karin M. Nuclear factor-B: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med. 1997;336:1066-71. [PMID: 9091804] CrossrefMedlineGoogle Scholar6. Donovan CE, Mark DA, He HZ, Liou HC, Kobzik L, Wang Y, . NF-kappa B/Rel transcription factors: c-Rel promotes airway hyperresponsiveness and allergic pulmonary inflammation. J Immunol. 1999;163:6827-33. [PMID: 10586083] MedlineGoogle Scholar7. Ogryzko VV, Schiltz RL, Russanova V, Howard BH, Nakatani Y. The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell. 1996;87:953-9. [PMID: 8945521] CrossrefMedlineGoogle Scholar8. Roth SY, Denu JM, Allis CD. Histone acetyltransferases. Annu Rev Biochem. 2001;70:81-120. [PMID: 11395403] CrossrefMedlineGoogle Scholar9. Ito K, Barnes PJ, Adcock IM. Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin-1-induced histone H4 acetylation on lysines 8 and 12. Mol Cell Biol. 2000;20:6891-903. [PMID: 10958685] CrossrefMedlineGoogle Scholar10. Gao L, Cueto MA, Asselbergs F, Atadja P. Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family. J Biol Chem. 2002;277:25748-55. [PMID: 11948178] CrossrefMedlineGoogle Scholar11. Ito K, Caramori G, Lim S, Oates T, Chung KF, Barnes PJ, . Expression and activity of histone deacetylases in human asthmatic airways. Am J Respir Crit Care Med. 2002;166:392-6. [PMID: 12153977] CrossrefMedlineGoogle Scholar12. Barnes PJ. Anti-inflammatory actions of glucocorticoids: molecular mechanisms [Editorial]. Clin Sci (Lond). 1998;94:557-72. [PMID: 9854452] CrossrefMedlineGoogle Scholar13. Barnes PJ. Molecular mechanisms of corticosteroids in allergic diseases. Allergy. 2001;56:928-36. [PMID: 11576070] CrossrefMedlineGoogle Scholar14. Schwiebert LM, Stellato C, Schleimer RP. The epithelium as a target of glucocorticoid action in the treatment of asthma. Am J Respir Crit Care Med. 1996; 154:S16-9; discussion S19-20. [PMID: 8756782] Google Scholar15. Herrscher RF, Kasper C, Sullivan TJ. Endogenous cortisol regulates immunoglobulin E-dependent late phase reactions. J Clin Invest. 1992;90:596-603. [PMID: 1644926] CrossrefMedlineGoogle Scholar16. Barnes PJ. Therapeutic strategies for allergic diseases. Nature. 1999;402:B31-8. [PMID: 10586893] CrossrefMedlineGoogle Scholar17. Yudt MR, Cidlowski JA. The glucocorticoid receptor: coding a diversity of proteins and responses through a single gene. Mol Endocrinol. 2002;16:1719-26. [PMID: 12145329] CrossrefMedlineGoogle Scholar18. Leung DY, Hamid Q, Vottero A, Szefler SJ, Surs W, Minshall E, . Association of glucocorticoid insensitivity with increased expression of glucocorticoid receptor . J Exp Med. 1997;186:1567-74. [PMID: 9348314] CrossrefMedlineGoogle Scholar19. 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Molecular regulation of granulocyte macrophage colony-stimulating factor in human lung epithelial cells by interleukin (IL)-1, IL-4, and IL-13 involves both transcriptional and post-transcriptional mechanisms. Am J Respir Cell Mol Biol. 2000;22:582-9. [PMID: 10783130] CrossrefMedlineGoogle Scholar37. Caelles C, Gonzalez-Sancho JM, Munoz A. Nuclear hormone receptor antagonism with AP-1 by inhibition of the JNK pathway. Genes Dev. 1997;11:3351-64. [PMID: 9407028] CrossrefMedlineGoogle Scholar38. Vanden Berghe W, Vermeulen L, De Wilde G, De Bosscher K, Boone E, Haegeman G. Signal transduction by tumor necrosis factor and gene regulation of the inflammatory cytokine interleukin-6. Biochem Pharmacol. 2000;60:1185-95. [PMID: 11007957] CrossrefMedlineGoogle Scholar39. Lasa M, Brook M, Saklatvala J, Clark AR. Dexamethasone destabilizes cyclooxygenase 2 mRNA by inhibiting mitogen-activated protein kinase p38. Mol Cell Biol. 2001;21:771-80. [PMID: 11154265] CrossrefMedlineGoogle Scholar40. Lasa M, Abraham SM, Boucheron C, Saklatvala J, Clark AR. Dexamethasone causes sustained expression of mitogen-activated protein kinase (MAPK) phosphatase 1 and phosphatase-mediated inhibition of MAPK p38. Mol Cell Biol. 2002;22:7802-11. [PMID: 12391149] CrossrefMedlineGoogle Scholar41. Barnes PJ. Scientific rationale for inhaled combination therapy with long-acting 2-agonists and corticosteroids. Eur Respir J. 2002;19:182-91. [PMID: 11843317] CrossrefMedlineGoogle Scholar42. Adcock IM, Stevens DA, Barnes PJ. Interactions of glucocorticoids and 2-agonists. Eur Respir J. 1996;9:160-8. [PMID: 8834349] CrossrefMedlineGoogle Scholar43. Mak JC, Nishikawa M, Shirasaki H, Miyayasu K, Barnes PJ. Protective effects of a glucocorticoid on downregulation of pulmonary 2-adrenergic receptors in vivo. J Clin Invest. 1995;96:99-106. [PMID: 7615841] CrossrefMedlineGoogle Scholar44. Mak JC, Hisada T, Salmon M, Barnes PJ, Chung KF. Glucocorticoids reverse IL-1-induced impairment of -adrenoceptor-mediated relaxation and up-regulation of G-protein-coupled receptor kinases. Br J Pharmacol. 2002;135:987-96. [PMID: 11861327] CrossrefMedlineGoogle Scholar45. Eickelberg O, Roth M, Lorx R, Bruce V, Rudiger J, Johnson M, . Ligand-independent activation of the glucocorticoid receptor by 2-adrenergic receptor agonists in primary human lung fibroblasts and vascular smooth muscle cells. J Biol Chem. 1999;274:1005-10. [PMID: 9873044] CrossrefMedlineGoogle Scholar46. Pang L, Knox AJ. Regulation of TNF--induced eotaxin release from cultured human airway smooth muscle cells by 2-agonists and corticosteroids. FASEB J. 2001;15:261-269. [PMID: 11149914] CrossrefMedlineGoogle Scholar47. Korn SH, Wouters EF, Wesseling G, Arends JW, Thunnissen FB. Interaction between glucocorticoids and 2-agonists: and glucocorticoid-receptor mRNA expression in human bronchial epithelial cells. Biochem Pharmacol. 1998;56:1561-9. [PMID: 9973176] CrossrefMedlineGoogle Scholar48. Usmani OS, Maneechotesuwan K, Adcock IM, Barnes PJ. Glucocorticoid receptor activation following inhaled fluticasone and salmeterol [Abstract]. Am J Respir Crit Care Med. 2002;165:A616. Google Scholar49. Barnes PJ. Theophylline: new perspectives for an old drug. Am J Respir Crit Care Med. 2003;167:813-8. [PMID: 12623857] CrossrefMedlineGoogle Scholar50. Ito K, Lim S, Caramori G, Cosio B, Chung KF, Adcock IM, . A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression. Proc Natl Acad Sci U S A. 2002;99:8921-6. [PMID: 12070353] CrossrefMedlineGoogle Scholar51. Evans DJ, Taylor DA, Zetterstrom O, Chung KF, O'Connor BJ, Barnes PJ. A comparison of low-dose inhaled budesonide plus theophylline and high-dose inhaled budesonide for moderate asthma. N Engl J Med. 1997;337:1412-8. [PMID: 9358138] CrossrefMedlineGoogle Scholar52. Ukena D, Harnest U, Sakalauskas R, Magyar P, Vetter N, Steffen H, . Comparison of addition of theophylline to inhaled steroid with doubling of the dose of inhaled steroid in asthma. Eur Respir J. 1997;10:2754-60. [PMID: 9493656] CrossrefMedlineGoogle Scholar53. Lim S, Jatakanon A, Gordon D, Macdonald C, Chung KF, Barnes PJ. Comparison of high dose inhaled steroids, low dose inhaled steroids plus low dose theophylline, and low dose inhaled steroids alone in chronic asthma in general practice. Thorax. 2000;55:837-41. [PMID: 10992535] CrossrefMedlineGoogle Scholar54. Szefler SJ, Leung DY. Glucocorticoid-resistant asthma: pathogenesis and clinical implications for management. Eur Respir J. 1997;10:1640-7. [PMID: 9230260] CrossrefMedlineGoogle Scholar55. Barnes PJ. Steroid-resistant asthma. Eur Resp Rev. 2000;10:74-8. Google Scholar56. Spahn JD, Szefler SJ, Surs W, Doherty DE, Nimmagadda SR, Leung DY. A novel action of IL-13: induction of diminished monocyte glucocorticoid receptor-binding affinity. J Immunol. 1996;157:2654-9. [PMID: 8805670] MedlineGoogle Scholar57. Irusen E, Matthews JG, Takahashi A, Barnes PJ, Chung KF, Adcock IM. p38 Mitogen-activated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity: role in steroid-insensitive asthma. J Allergy Clin Immunol. 2002;109:649-57. [PMID: 11941315] CrossrefMedlineGoogle Scholar58. Hamid QA, Wenzel SE, Hauk PJ, Tsicopoulos A, Wallaert B, Lafitte JJ, . Increased glucocorticoid receptor in airway cells of glucocorticoid-insensitive asthma. Am J Respir Crit Care Med. 1999;159:1600-4. [PMID: 10228133] CrossrefMedlineGoogle Scholar59. Gagliardo R, Chanez P, Vignola AM, Bousquet J, Vachier I, Godard P, . Glucocorticoid receptor and in glucocorticoid dependent asthma. Am J Respir Crit Care Med. 2000;162:7-13. [PMID: 10903212] CrossrefMedlineGoogle Scholar60. Corrigan CJ, Brown PH, Barnes NC, Szefler SJ, Tsai JJ, Frew AJ, . Glucocorticoid resistance in chronic asthma. Glucocorticoid pharmacokinetics, glucocorticoid receptor characteristics, and inhibition of peripheral blood T cell proliferation by glucocorticoids in vitro. Am Rev Respir Dis. 1991;144:1016-25. [PMID: 1952426] CrossrefMedlineGoogle Scholar61. Adcock IM, Lane SJ, Brown CR, Lee TH, Barnes PJ. Abnormal glucocorticoid receptor-activator protein 1 interaction in steroid-resistant asthma. J Exp Med. 1995;182:1951-8. [PMID: 7500041] CrossrefMedlineGoogle Scholar62. Matthews JG, Ito K, Barnes PJ, Adcock IM. Corticosteroid-resistant and corticosteroid-dependent asthma: two clinical phenotypes can be associated with the same in vitro defects in nuclear translocation and acetylation of histone 4 [Abstract]. Am J Respir Crit Care Med. 2000;161:A189. Google Scholar63. Keatings VM, Jatakanon A, Worsdell YM, Barnes PJ. Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD. Am J Respir Crit Care Med. 1997;155:542-8. [PMID: 9032192] CrossrefMedlineGoogle Scholar64. Culpitt SV, Maziak W, Loukidis S, Nightingale JA, Matthews JL, Barnes PJ. Effect of high dose inhaled steroid on cells, cytokines, and proteases in induced sputum in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999;160:1635-9. [PMID: 10556133] CrossrefMedlineGoogle Scholar65. Nightingale JA, Rogers DF, Fan Chung K, Barnes PJ. No effect of inhaled budesonide on the response to inhaled ozone in normal subjects. Am J Respir Crit Care Med. 2000;161:479-86. [PMID: 10673189] CrossrefMedlineGoogle Scholar66. Culpitt SV, Rogers DF, Shah P, De Matos C, Russell RE, Donnelly LE, . Impaired inhibition by dexamethasone of cytokine release by alveolar macrophages from patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003;167:24-31. [PMID: 12406856] CrossrefMedlineGoogle Scholar67. Ito K, Lim S, Caramori G, Chung KF, Barnes PJ, Adcock IM. Cigarette smoking reduces histone deacetylase 2 expression, enhances cytokine expression, and inhibits glucocorticoid actions in alveolar macrophages. FASEB J. 2001;15:1110-2. [PMID: 11292684] CrossrefMedlineGoogle Scholar68. Ito K, Watanabe S, Kharitonov S, Hanazawa T, Adcock IM, Barnes PJ. Histone deacetylase activity and gene expression in COPD patients [Abstract]. Eur Respir J. 2001;18:316S. MedlineGoogle Scholar69. Montuschi P, Collins JV, Ciabattoni G, Lazzeri N, Corradi M, Kharitonov SA, . Exhaled 8-isoprostane as an in vivo biomarker of lung oxidative stress in patients with COPD and healthy smokers. Am J Respir Crit Care Med. 2000;162:1175-7. [PMID: 10988150] CrossrefMedlineGoogle Scholar70. Barnes PJ, Pedersen S, Busse WW. Efficacy and safety of inhaled corticosteroids. New developments. Am J Respir Crit Care Med. 1998;157:S1-53. [PMID: 9520807] CrossrefMedlineGoogle Scholar71. Heck S, Kullmann M, Gast A, Ponta H, Rahmsdorf HJ, Herrlich P, . A distinct modulating domain in glucocorticoid receptor monomers in the repression of activity of the transcription factor AP-1. EMBO J. 1994;13:4087-95. [PMID: 8076604] CrossrefMedlineGoogle Scholar72. Adcock IM, Nasuhara Y, Stevens DA, Barnes PJ. Ligand-induced differentiation of glucocorticoid receptor (GR) trans-repression and transactivation: preferential targetting of NF-B and lack of I-B involvement. Br J Pharmacol. 1999;127:1003-11. [PMID: 10433509] CrossrefMedlineGoogle Scholar73. Vayssiere BM, Dupont S, Choquart A, Petit F, Garcia T, Marchandeau C, . Synthetic glucocorticoids that dissociate transactivation and AP-1 transrepression exhibit antiinflammatory activity in vivo. Mol Endocrinol. 1997;11:1245-55. [PMID: 9259316] CrossrefMedlineGoogle Scholar74. Belvisi MG, Wicks SL, Battram CH, Bottoms SE, Redford JE, Woodman P, . Therapeutic benefit of a dissociated glucocorticoid and the relevance of in vitro separation of transrepression from transactivation activity. J Immunol. 2001;166:1975-82. [PMID: 11160246] CrossrefMedlineGoogle Scholar75. Bledsoe RK, Montana VG, Stanley TB, Delves CJ, Apolito CJ, McKee DD, . Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition. Cell. 2002;110:93-105. [PMID: 12151000] CrossrefMedlineGoogle Scholar76. Barnes PJ. New treatments for COPD. Nat Rev Drug Discov. 2002;1:437-46. [PMID: 12119745] CrossrefMedlineGoogle Scholar77. Ito K, Lim S, Chung KF, Barnes PJ, Adcock IM. Theophylline enhances histone deacetylase activity and restores glucocorticoid function during oxidative stress [Abstract]. Am J Respir Crit Care Med. 2002;165:A625. Google Scholar Author, Article, and Disclosure InformationAffiliations: From National Heart and Lung Institute, Imperial College, London, United Kingdom. Disclosures:Grants received: P.J. Barnes, I.M. Adcock (GlaxoSmithKline and AstraZeneca); Grants pending: P.J. Barnes, I.M. Adcock (GlaxoSmithKline and AstraZeneca).Corresponding Author: P.J. Barnes, DM, DSc, Department of Thoracic Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, United Kingdom; e-mail, p.j.[email protected]ac.uk. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByNanotechnology based advanced therapeutic strategies for targeting interleukins in chronic respiratory diseasesLipopolysaccharide Regulates Pro- and Anti-Inflammatory Cytokines, Corticosterone, and Melatonin in ToadsThe central role of IL-33/IL-1RL1 pathway in asthma: From pathogenesis to interventionAsthma and COVID-19: Emphasis on Adequate of as of and as a Effect of the resistance in asthma: and molecular effects of on a of allergic between and and gene expression of glucocorticoid and receptors from the for of human respiratory with glucocorticoids in the treatment of asthma: of the oral corticosteroids and persistent in from the asthma to bronchial asthma as for A of of Melatonin and Glucocorticoid with in the a between Melatonin and of in Steroid Drug by of proteins during the Efficacy of to in a of corticosteroids in asthma: the between and the novel mode of action of the Association and 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Annals of Internal Medicine · review · 370 citationsread the source →

An overview of four studies of a continuous oral contraceptive (levonorgestrel 90 mcg/ethinyl estradiol 20 mcg) on premenstrual dysphoric disorder and premenstrual syndrome.

Background: This article presents an overview of four studies that evaluated a continuous oral contraceptive (OC) containing levonorgestrel (90 mcg) and ethinyl estradiol (20 mcg; LNG/EE) for managing premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS). Study design: Three randomized, double-blind, placebo-controlled trials and one open-label, single-treatment substudy examined mean changes from baseline in the Daily Record of Severity of Problems (DRSP) or Penn Daily Symptom Rating (DSR). Results: Improvements from baseline in mean DRSP and DSR scores were observed, but results were not consistent among the studies. Mean percent improvement of premenstrual symptoms ranged from 30% to 59% in controlled trials and 56% to 81% in an open-label substudy. A large placebo effect was also observed in the placebo-controlled studies. Continuous LNG/EE yielded a favorable safety profile. Conclusions: These data, although not consistent, indicate that continuous LNG/EE may reduce the symptoms of PMDD and PMS, providing an option for women who are appropriate candidates for a continuous OC as a contraceptive, the approved indication for this medication.

Contraception · review · 59 citationsread the source →

Test of mindfulness and hope components in a psychological intervention for women with cancer recurrence.

OBJECTIVE: Psychological interventions can attenuate distress and enhance coping for those with an initial diagnosis of cancer, but there are few intervention options for individuals with cancer recurrence. To address this gap, we developed and tested a novel treatment combining Mindfulness, Hope Therapy, and biobehavioral components. METHOD: An uncontrolled, repeated measures design was used. Women (N = 32) with recurrent breast or gynecologic cancers were provided 20 treatment sessions in individual (n = 12) or group (n = 20) formats. On average, participants were middle aged (M = 58) and Caucasian (81%). Independent variables (i.e., hope and mindfulness) and psychological outcomes (i.e., depression, negative mood, worry, and symptoms of generalized anxiety disorder) were assessed pre-treatment and 2, 4, and 7 months later. Session-by-session therapy process (positive and negative affect, quality-of-life) and mechanism (use of intervention-specific skills) measures were also included. RESULTS: Distress, anxiety, and negative affect decreased, whereas positive affect and mental-health-related quality-of-life increased over the course of treatment, as demonstrated in mixed-effects models with the intent-to-treat sample. Both hope and mindfulness increased, and use of mindfulness skills was related to decreased anxiety. CONCLUSIONS: This treatment was feasible to deliver and was acceptable to patients. The trial serves as preliminary evidence for a multi-component intervention tailored to treat difficulties specific to recurrent cancer. The blending of the components was novel as well as theoretically and practically consistent. A gap in the literature is addressed, providing directions for testing interventions designed for patients coping with the continuing stressors and challenges of cancer recurrence.

Journal of Consulting and Clinical Psychology · 72 citationsread the source →

How intra-familial decision-making affects women's access to, and use of maternal healthcare services in Ghana: a qualitative study.

Background: There is some evidence to suggest that within the household, family and community settings, women in sub-Saharan Africa often have limited autonomy and control over their reproductive health decisions. However, there are few studies that examine how intra-familial decision-making power may affect women's ability to access and use maternal health services. The purpose of this paper is to examine how intra-familial decision-making affects women's ability to access and use maternal health services. Methods: We conducted 12 focus group discussions and 81 individual interviews with a total of 185 expectant and lactating mothers in six communities in Ghana. In addition, 20 key informant interviews were completed with healthcare providers. Attride-Stirling's thematic network analysis framework was used to analyse the data. Results: Findings suggest that decision-making regarding access to and use of skilled maternal healthcare services is strongly influenced by the values and opinions of husbands, mothers-in-law, traditional birth attendants and other family and community members, more than those of individual childbearing women. In 49.2%, 16.2%, and 12.4% of cases in which women said they were unable to access maternal health services during their last pregnancy, husbands, mothers-in-law, and husband plus mothers-in-law, respectively, made the decision. Women themselves were the final decision-makers in only 2.7% of the cases. The findings highlight how the goal of improving access to maternal healthcare services can be undermined by women's lack of decision-making autonomy through complex processes of gender inequality, economic marginalisation, communal decision-making and social power. Conclusion: Interventions to improve women's use of maternity services should move beyond individual women to target different stakeholders at multiple levels, including husbands and mothers-in-law.

BMC pregnancy and childbirth · 105 citationsread the source →

"There Was a Sense That Our Load Had Been Lightened": Evaluating Outcomes of Virtual Ethics Rounds for Veterinary Team Members.

Clinical ethics support services (CESS) are employed in healthcare to improve patient care and help team members develop skills to recognize and navigate ethically challenging situations (ECS). The objective of this study was to evaluate the impact of ethics rounds, one form of CESS, on veterinary team members. An anonymous, online mixed-methods survey incorporating a 15-item instrument designed to assess the outcomes of moral case deliberation originally developed for human healthcare workers (the Euro-MCD 2.0), was developed. The survey was administered to veterinary team members prior to and following participation in a 90-min virtual ethics rounds session. A total of 23 sessions of virtual ethics rounds were held. In total, 213 individuals participated, and 89 completed both surveys (response rate 41.8%). Most respondents were female (n = 70, 81%). Most were veterinarians (n = 51, 59%), followed by other veterinary team members (practice manager, animal attendant) (n = 18, 21%), veterinary nurses or animal health technicians (n = 10, 12%) and veterinary students (n = 8, 9%). Age ranged from 20 to 73 (median 41, IQR 32-52, n = 87). While there was no statistically significant difference between overall modified Euro-MCD 2.0 scores between T1 and T2, there were statistically significant changes in 7 out of 15 Euro-MCD 2.0 items in the domains of moral competence and moral teamwork. Reflexive thematic analysis of free-text responses identified themes including the types, impact and barriers to resolving ECS, the impacts of ethics rounds on veterinary team members and constraints preventing veterinary team members from speaking up in the face of ECS. While participants largely described the impact of ethics rounds as beneficial (for example, by facilitating clarification of thinking about ECS, allowing participants to see ECS from the perspective of others and providing a safe space for discussion), reflecting on ECS could be stressful for participants. Active participation in ethics rounds may be inhibited in the context of power imbalance, or in settings where bullying occurs. Overall, carefully facilitated ethics rounds has the potential to improve the ability of veterinary team members to identify and navigate ECS, and potentially mitigate moral distress.

Frontiers in veterinary science · 8 citationsread the source →

Burden, risk factors, and comorbidities of behavioural and emotional problems in Kenyan children: a population-based study.

Background: Three-quarters of the burden of mental health problems occurs in low-and-middle-income countries, but few epidemiological studies of these problems in preschool children from sub-Saharan Africa have been published. Behavioural and emotional problems often start in early childhood, and this might be particularly important in Africa, where the incidence of perinatal and early risk factors is high. We therefore aimed to estimate the prevalence and risk factors of behavioural and emotional problems in young children in a rural area on the Kenyan coast. Methods: We did a population-based epidemiological study to assess the burden of behavioural and emotional problems in preschool children and comorbidities in the Kilifi Health and Demographic Surveillance System (KHDSS, a database formed of the population under routine surveillance linked to admissions to Kilifi County Hospital). We used the Child Behaviour Checklist (CBCL) to assess behavioural and emotional problems. We then determined risk factors and medical comorbidities associated with behavioural and emotional problems. The strength of associations between the risk factors and the behavioural and emotional problems was estimated using generalised linear models, with appropriate distribution and link functions. Findings: 3539 families were randomly selected from the KHDSS. Of these, 3273 children were assessed with CBCL. The prevalence of total behavioural and emotional problems was 13% (95% CI 12-14), for externalising problems was 10% (9-11), and for internalising problems was 22% (21-24). The most common CBCL syndrome was somatic problems (21%, 20-23), whereas the most common DSM-IV-oriented scale was anxiety problems (13%, 12-14). Factors associated with total problems included consumption of cassava (risk ratio 5·68, 95% CI 3·22-10·03), perinatal complications (4·34, 3·21-5·81), seizure disorders (2·90, 2·24-3·77), and house status (0·11, 0·08-0·14). Seizure disorders, burn marks, and respiratory problems were important comorbidities of behavioural and emotional problems. Interpretation: Behavioural and emotional problems are common in preschool children in this Kenyan rural area and are associated with preventable risk factors. Behavioural and emotional problems and associated comorbidities should be identified and addressed in young children. Funding: Wellcome Trust.

The lancet. Psychiatry · 43 citationsread the source →

Brief teacher training improves student behavior and student-teacher relationships in middle school.

Despite research demonstrating the importance of student-teacher relationships for student functioning, little is known about strategies to enhance such relationships, particularly in secondary school. The current study examined effects of a professional development for middle school teachers on the Establish-Maintain-Restore (EMR) approach. EMR aims to enhance teachers' skills in cultivating relationships with students and involves brief training (3 hr) and ongoing implementation supports. In a randomized controlled trial, 20 teachers and 190 students were assigned to EMR or control. Observers rated academically engaged time and disruptive behavior, and teachers reported on relationship quality. Multilevel models showed that EMR resulted in significant improvements in student-teacher relationships (Hedge's g = .61, 95% CI [0.21, 1.02]), academically engaged time (g = .81, 95% CI [0.01, 1.63]), and disruptive behavior (g = 1.07, 95% CI [0.01, 2.16]). Results indicate potential promise for EMR. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

School psychology (Washington, D.C.) · 22 citationsread the source →

Fertility-related knowledge and reproductive goals in childhood cancer survivors: short communication.

Study question: Do young adult survivors of childhood cancer know their fertility status, in the context of their parenthood goals and screening for gonadal functioning? Summary answer: While 80% of survivors (who were without children) wanted children in the future, most did not know their fertility status, and screening for gonadal functioning was underutilized. What is known already: Survivors of childhood cancer are at risk for infertility, but fertility counseling and assessment are underutilized. Separate studies indicated that survivors' fertility-related knowledge is poor and that they often wanted to have children. Yet, studies have not investigated the intersection of both issues, as well as potential distress if parenthood goals are not met. Study design, size, duration: Young adult male and female survivors of childhood cancer (N = 149) completed cross-sectional surveys, and data for those without children (n = 105, 70.5%) are presented here. Participants/materials, setting, methods: Participants were 20-40 years old (M = 26.5), diagnosed 5-33 years prior to study participation, and completed questionnaires online. Knowledge of fertility status, parenthood goals, and potential distress if survivors were unable to have children were assessed. Medical records were reviewed for hormone levels as indicators of screening for gonadal functioning. Main results and the role of chance: Most survivors (n = 81; 77.1%) did not know their fertility status, while over 80% (n = 89) wanted children (neither aspect varied by socio-demographic/cancer-specific factors). Two-thirds of survivors indicated they would be distressed if parenthood goals remained unfulfilled; especially female (versus male, t = 2.64; P = 0.01) or partnered (versus single, t = -3.45; P < 0.001) survivors. Forty survivors (38.1%) had documented assessments of gonadal functioning, of which 33 (82.5%) reported not knowing their fertility status. Limitations, reasons for caution: Relevant risk factors may have not been identified owing to limited sample size and missing treatment information. The underutilization of screening for gonadal functioning needs further exploration in other pediatric centers. Wider implications of the findings: Most adult childhood cancer survivors want to become parents, but do not know their fertility status, which could cause significant psychological distress. Healthcare providers should continuously address fertility among survivors, but more research is needed on how to implement routine fertility counseling and/or testing. Study funding/competing interest(s): This study was funded by the Research Institute at Nationwide Children's Hospital (V.L.) and Dutch Cancer Society (RUG2009-4442, M.A.T.). All authors have no conflict of interest to declare.

Human reproduction (Oxford, England) · 52 citationsread the source →

The impact of frailty on ICU and 30-day mortality and the level of care in very elderly patients (≥ 80 years).

Purpose: Very old critical ill patients are a rapid expanding group in the ICU. Indications for admission, triage criteria and level of care are frequently discussed for such patients. However, most relevant outcome studies in this group frequently find an increased mortality and a reduced quality of life in survivors. The main objective was to study the impact of frailty compared with other variables with regards to short-term outcome in the very old ICU population. Methods: A transnational prospective cohort study from October 2016 to May 2017 with 30 days follow-up was set up by the European Society of Intensive Care Medicine. In total 311 ICUs from 21 European countries participated. The ICUs included the first consecutive 20 very old (≥ 80 years) patients admitted to the ICU within a 3-month inclusion period. Frailty, SOFA score and therapeutic procedures were registered, in addition to limitations of care. For measurement of frailty the Clinical Frailty Scale was used at ICU admission. The main outcomes were ICU and 30-day mortality and survival at 30 days. Results: A total of 5021 patients with a median age of 84 years (IQR 81-86 years) were included in the final analysis, 2404 (47.9%) were women. Admission was classified as acute in 4215 (83.9%) of the patients. Overall ICU and 30-day mortality rates were 22.1% and 32.6%. During ICU stay 23.8% of the patients did not receive specific ICU procedures: ventilation, vasoactive drugs or renal replacement therapy. Frailty (values ≥ 5) was found in 43.1% and was independently related to 30-day survival (HR 1.54; 95% CI 1.38-1.73) for frail versus non-frail. Conclusions: Among very old patients (≥ 80 years) admitted to the ICU, the consecutive classes in Clinical Frailty Scale were inversely associated with short-term survival. The scale had a very low number of missing data. These findings provide support to add frailty to the clinical assessment in this patient group. Trial registration: ClinicalTrials.gov (ID: NCT03134807).

Intensive care medicine · 338 citationsread the source →

Prevalence and Nature of Sexist and Racial/Ethnic Microaggressions Against Surgeons and Anesthesiologists.

Importance: Workplace mistreatment can manifest as microaggressions that cause chronic, severe distress. As physician burnout becomes a global crisis, quantitative research to delineate the impact of microaggressions is imperative. Objectives: To examine the prevalence and nature of sexist and racial/ethnic microaggressions against female and racial/ethnic-minority surgeons and anesthesiologists and assess the association with physician burnout. Design, setting, and participants: This cross-sectional survey evaluated microaggressions and physician burnout within a diverse cohort of surgeons and anesthesiologists in a large health maintenance organization. A total of 1643 eligible participants were sent a recruitment email on January 8, 2020, 1609 received the email, and 652 replied, for a response rate of 41%. The study survey remained open until February 20, 2020. A total of 588 individuals (37%) were included in the study after exclusion criteria were applied. Exposures: The Maslach Burnout Inventory, the Racial Microaggression Scale, and the Sexist Microaggression Experience and Stress Scale. Main outcomes and measures: The primary outcomes were prevalence and nature of sexist and racial/ethnic microaggressions against female and racial/ethnic-minority surgeons and anesthesiologists using the Sexist Microaggression Experience and Stress Scale and Racial Microaggression Scale. Secondary outcomes were frequency and severity of microaggressions, prevalence of physician burnout, and associations between microaggressions and physician burnout. Results: Data obtained from 588 respondents (249 [44%] female, 367 [62%] racial/ethnic minority, 224 [38.1%] 40-49 years of age) were analyzed. A total of 245 of 259 female respondents (94%) experienced sexist microaggressions, most commonly overhearing or seeing degrading female terms or images. Racial/ethnic microaggressions were experienced by 299 of 367 racial/ethnic-minority physicians (81%), most commonly reporting few leaders or coworkers of the same race/ethnicity. Criminality was rare (18 of 367 [5%]) but unique to and significantly higher for Hispanic and Black physicians. Individuals who identified as underrepresented minorities were more likely to experience environmental inequities (odds ratio [OR], 4.21; 95% CI, 1.6-10.75; P = .002) and criminality (OR, 14.93; 95% CI, 4.5-48.5; P < .001). The prevalence of physician burnout was 47% (280 of 588 physicians) and higher among female physicians (OR, 1.60; 95% CI, 1.03-2.47; P = .04) and racial/ethnic-minority physicians (OR, 2.08; 95% CI, 1.31-3.30; P = .002). Female physicians who experienced sexist microaggressions (racial/ethnic-minority female physicians: OR, 1.84; 95% CI, 1.04-3.25; P = .04; White female physicians: OR, 1.99; 95% CI, 1.07-3.69; P = .03) were more likely to experience burnout. Racial/ethnic-minority female physicians (OR, 1.86; 95% CI, 1.03-3.35; P = .04) who experienced racial microaggressions were more likely to report burnout. Racial/ethnic-minority female physicians who had the compound experience of sexist and racial/ethnic microaggressions (OR, 2.05; 95% CI, 1.14-3.69; P = .02) were more likely to experience burnout. Conclusions and relevance: The prevalence of sexist and racial/ethnic microaggressions against female and racial/ethnic-minority surgeons and anesthesiologists was high and associated with physician burnout. This study provides a valuable response to the increasing call for evidence-based data on surgical workplace mistreatment.

JAMA surgery · 99 citationsread the source →