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المكتبة البحثية60 results
Peer-reviewed works with DOI and abstract, discovered from MEDLINE-indexed literature. Candidates: no tier, no stated finding, not yet read.
Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic.
Background: Before the COVID-19 pandemic, coronaviruses caused two noteworthy outbreaks: severe acute respiratory syndrome (SARS), starting in 2002, and Middle East respiratory syndrome (MERS), starting in 2012. We aimed to assess the psychiatric and neuropsychiatric presentations of SARS, MERS, and COVID-19.
Methods: In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases (from their inception until March 18, 2020), and medRxiv, bioRxiv, and PsyArXiv (between Jan 1, 2020, and April 10, 2020) were searched by two independent researchers for all English-language studies or preprints reporting data on the psychiatric and neuropsychiatric presentations of individuals with suspected or laboratory-confirmed coronavirus infection (SARS coronavirus, MERS coronavirus, or SARS coronavirus 2). We excluded studies limited to neurological complications without specified neuropsychiatric presentations and those investigating the indirect effects of coronavirus infections on the mental health of people who are not infected, such as those mediated through physical distancing measures such as self-isolation or quarantine. Outcomes were psychiatric signs or symptoms; symptom severity; diagnoses based on ICD-10, DSM-IV, or the Chinese Classification of Mental Disorders (third edition) or psychometric scales; quality of life; and employment. Both the systematic review and the meta-analysis stratified outcomes across illness stages (acute vs post-illness) for SARS and MERS. We used a random-effects model for the meta-analysis, and the meta-analytical effect size was prevalence for relevant outcomes, I2 statistics, and assessment of study quality.
Findings: 1963 studies and 87 preprints were identified by the systematic search, of which 65 peer-reviewed studies and seven preprints met inclusion criteria. The number of coronavirus cases of the included studies was 3559, ranging from 1 to 997, and the mean age of participants in studies ranged from 12·2 years (SD 4·1) to 68·0 years (single case report). Studies were from China, Hong Kong, South Korea, Canada, Saudi Arabia, France, Japan, Singapore, the UK, and the USA. Follow-up time for the post-illness studies varied between 60 days and 12 years. The systematic review revealed that during the acute illness, common symptoms among patients admitted to hospital for SARS or MERS included confusion (36 [27·9%; 95% CI 20·5-36·0] of 129 patients), depressed mood (42 [32·6%; 24·7-40·9] of 129), anxiety (46 [35·7%; 27·6-44·2] of 129), impaired memory (44 [34·1%; 26·2-42·5] of 129), and insomnia (54 [41·9%; 22·5-50·5] of 129). Steroid-induced mania and psychosis were reported in 13 (0·7%) of 1744 patients with SARS in the acute stage in one study. In the post-illness stage, depressed mood (35 [10·5%; 95% CI 7·5-14·1] of 332 patients), insomnia (34 [12·1%; 8·6-16·3] of 280), anxiety (21 [12·3%; 7·7-17·7] of 171), irritability (28 [12·8%; 8·7-17·6] of 218), memory impairment (44 [18·9%; 14·1-24·2] of 233), fatigue (61 [19·3%; 15·1-23·9] of 316), and in one study traumatic memories (55 [30·4%; 23·9-37·3] of 181) and sleep disorder (14 [100·0%; 88·0-100·0] of 14) were frequently reported. The meta-analysis indicated that in the post-illness stage the point prevalence of post-traumatic stress disorder was 32·2% (95% CI 23·7-42·0; 121 of 402 cases from four studies), that of depression was 14·9% (12·1-18·2; 77 of 517 cases from five studies), and that of anxiety disorders was 14·8% (11·1-19·4; 42 of 284 cases from three studies). 446 (76·9%; 95% CI 68·1-84·6) of 580 patients from six studies had returned to work at a mean follow-up time of 35·3 months (SD 40·1). When data for patients with COVID-19 were examined (including preprint data), there was evidence for delirium (confusion in 26 [65%] of 40 intensive care unit patients and agitation in 40 [69%] of 58 intensive care unit patients in one study, and altered consciousness in 17 [21%] of 82 patients who subsequently died in another study). At discharge, 15 (33%) of 45 patients with COVID-19 who were assessed had a dysexecutive syndrome in one study. At the time of writing, there were two reports of hypoxic encephalopathy and one report of encephalitis. 68 (94%) of the 72 studies were of either low or medium quality.
Interpretation: If infection with SARS-CoV-2 follows a similar course to that with SARS-CoV or MERS-CoV, most patients should recover without experiencing mental illness. SARS-CoV-2 might cause delirium in a significant proportion of patients in the acute stage. Clinicians should be aware of the possibility of depression, anxiety, fatigue, post-traumatic stress disorder, and rarer neuropsychiatric syndromes in the longer term.
Funding: Wellcome Trust, UK National Institute for Health Research (NIHR), UK Medical Research Council, NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London.
The lancet. Psychiatry · meta-analysis · 1531 citationsread the source →
Pre-intervention distress moderates the efficacy of psychosocial treatment for cancer patients: a meta-analysis.
This meta-analysis examined whether effects of psychosocial interventions on psychological distress in cancer patients are conditional upon pre-intervention distress levels. Published articles and unpublished dissertations between 1980 and 2005 were searched for interventions reporting the Hospital Anxiety and Depression Scale (HADS) or the Spielberger State-Trait Anxiety Inventory (STAI). Multilevel mixed-effects modeling was used to meta-analyze effect-sizes separately for the HADS (27 trials, 2,424 patients) and STAI (34 trials, 2,029 patients). Pre-intervention distress significantly moderated intervention effects, explaining up to 50% of the between-study effect-size variance: effects on anxiety and depression were generally negligible when pre-intervention distress was low and pronounced when it was high. These results could not be explained by differences in intervention type, setting, dose, and whether intervention was targeted at distressed patients. Psychosocial interventions may be most beneficial for cancer patients with elevated distress. Future research should identify which treatment components are most effective for these patients to facilitate optimal treatment tailoring and cost-effective health care.
Journal of behavioral medicine · meta-analysis · 122 citationsread the source →
Tyler R, Cacace A, Stocking C, Tarver B, Engineer N, Martin J, Deshpande A, Stecker N, Pereira M, Kilgard M, Burress C, Pierce D, Rennaker R, Vanneste S. (2017)MEDLINE-indexed journal, not yet read by usScientific reports · randomised controlled trial Vagus Nerve Stimulation Paired with Tones for the Treatment of Tinnitus: A Prospective Randomized Double-blind Controlled Pilot Study in Humans.
The aim of the pilot study was to evaluate the effect of Vagus Nerve Stimulation (VNS) paired with sounds in chronic tinnitus patients. All participants were implanted and randomized to a paired VNS (n = 16) or control (n = 14) group. After 6 weeks of home therapy, all participants received paired VNS. The device was used on 96% of days with good compliance. After 6 weeks, the paired VNS group improved on the Tinnitus Handicap Inventory (THI) (p = 0.0012) compared to controls (p = 0.1561). The between-group difference was 10.3% (p = 0.3393). Fifty percent of the participants in the paired VNS group showed clinically meaningful improvements compared to 28% in controls. At one year, 50% of participants had a clinically meaningful response. The therapy had greater benefits for participants with tonal and non-blast induced tinnitus at the end of 6 (24.3% vs. 2%, p = 0.05) and 12 weeks (34% vs. 2%, p = 0.004) compared to controls with 80% and 70% responding at 6 months and 1 year, respectively. Adverse effects were mild and well-tolerated and the therapy had a similar safety profile to VNS for epilepsy. VNS paired with tones may be effective for a subgroup of tinnitus patients and provides impetus for a larger pivotal study.
Scientific reports · randomised controlled trial · 126 citationsread the source →
Antidepressants for depression in adults with HIV infection.
Background: Rates of major depression among people living with HIV (PLWH) are substantially higher than those seen in the general population and this may adversely affect antiretroviral treatment outcomes. Several unique clinical and psychosocial factors may contribute to the development and persistence of depression in PLWH. Given these influences, it is unclear if antidepressant therapy is as effective for PLWH as the general population.
Objectives: To assess the efficacy of antidepressant therapy for treatment of depression in PLWH.
Search methods: We searched The Cochrane Common Mental Disorders Group's specialised register (CCMD-CTR), the Cochrane Library, PubMed, Embase and ran a cited reference search on the Web of Science for reports of all included studies. We conducted additional searches of the international trial registers including; ClinicalTrials.gov, World Health Organization Trials Portal (ICTRP), and the HIV and AIDS - Clinical trials register. We searched grey literature and reference lists to identify additional studies and contacted authors to obtain missing data. We applied no restrictions on date, language or publication status to the searches, which included studies conducted between 1 January 1980 and 18 April 2017.
Selection criteria: We included randomized controlled trials of antidepressant drug therapy compared to placebo or another antidepressant drug class. Participants eligible for inclusion had to be aged 18 years and older, from any setting, and have both HIV and depression. Depression was defined according to Diagnostic and Statistical Manual of Mental Disorders or International Statistical Classification of Diseases criteria.
Data collection and analysis: Two review authors independently applied the inclusion criteria and extracted data. We presented categorical outcomes as risk ratios (RR) with 95% confidence intervals (CIs). Continuous outcomes were presented mean (MD) or standardized mean differences (SMD) with standard deviations (SD). We assessed quality of evidence using the GRADE approach.
Main results: We included 10 studies with 709 participants in this review. Of the 10 studies, eight were conducted in high income countries (USA and Italy), seven were conducted prior to 2000 and seven had predominantly men. Seven studies assessed antidepressants versus placebo, two compared different antidepressant classes and one had three arms comparing two antidepressant classes with placebo. Antidepressant therapy may result in a greater improvement in depression compared to placebo. There was a moderate improvement in depression when assessed with the Hamilton Depression Rating Scale (HAM-D) score as a continuous outcome (SMD 0.59, 95% CI 0.21 to 0.96; participants = 357; studies = 6; I2 = 62%, low quality evidence). However, there was no evidence of improvement when this was assessed with HAM-D score as a dichotomized outcome (RR 1.10, 95% CI 0.89 to 1.35; participants = 434; studies = 5; I2 = 0%, low quality evidence) or Clinical Global Impression of Improvement (CGI-I) score (RR 1.28, 95% CI 0.93 to 1.77; participants = 346; studies = 4; I2 = 29%, low quality evidence). There was little to no difference in the proportion of study dropouts between study arms (RR 1.28, 95% CI 0.91 to 1.80; participants = 306; studies = 4; I2 = 0%, moderate quality evidence).The methods of reporting adverse events varied substantially between studies, this resulted in very low quality evidence contributing to a pooled estimate (RR 0.88, 95% CI 0.64 to 1.21; participants = 167; studies = 2; I2 = 34%; very low quality evidence). Based on this, we were unable to determine if there was a difference in the proportion of participants experiencing adverse events in the antidepressant versus placebo arms. However, sexual dysfunction was reported commonly in people receiving selective serotonin reuptake inhibitors (SSRIs). People receiving tricyclic antidepressants (TCAs) frequently reported anticholinergic adverse effects such as dry mouth and constipation. There were no reported grade 3 or 4 adverse events in any study group. There was no evidence of a difference in follow-up CD4 count at study termination (MD -6.31 cells/mm3, 95% CI -72.76 to 60.14; participants = 176; studies = 3; I2 = 0%; low quality evidence). Only one study evaluated quality of life score (MD 3.60, 95% CI -0.38 to 7.58; participants = 87; studies = 1; very low quality evidence), due to the poor quality evidence we could not draw conclusions for this outcome. There were few studies comparing different antidepressant classes. We are uncertain if SSRIs differ from TCAs with regard to improvement in depression as evaluated by HAM-D score (MD -3.20, 95% CI -10.87 to 4.47; participants = 14; studies = 1; very low quality evidence). There was some evidence that mirtazapine resulted in a greater improvement in depression compared to an SSRI (MD 9.00, 95% CI 3.61 to 14.39; participants = 70; studies = 1; low quality evidence); however, this finding was not consistent for all measures of improvement in depression for this comparison. No studies reported on virological suppression or any other HIV specific outcomes. The studies included in this review had an overall unclear or high risk of bias due to under-reporting of study methods, high risk of attrition bias and inadequate sequence generation methods. Heterogeneity between studies and the limited number of participants, and events lead to downgrading of the quality of the evidence for several outcomes.
Authors' conclusions: This review demonstrates that antidepressant therapy may be more beneficial than placebo for the treatment of depression in PLWH. The low quality of the evidence contributing to this assessment and the lack of studies representing PLWH from generalized epidemics in low- to middle-income countries make the relevance of these finding in today's context limited. Future studies that evaluate the effectiveness of antidepressant therapy should be designed and conducted rigorously. Such studies should incorporate evaluation of stepped care models and health system strengthening interventions in the study design. In addition, outcomes related to HIV care and antiretroviral therapy should be reported.
The Cochrane database of systematic reviews · meta-analysis · 24 citationsread the source →
Little P, Stuart B, Hobbs FR, Kelly J, Smith ER, Bradbury KJ, Hughes S, Smith PW, Moore MV, Lean ME, Margetts BM, Byrne CD, Griffin S, Davoudianfar M, Hooper J, Yao G, Zhu S, Raftery J, Yardley L. (2016)MEDLINE-indexed journal, not yet read by usThe lancet. Diabetes & endocrinology · randomised controlled trial 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 →
Patel V, Weobong B, Weiss HA, Anand A, Bhat B, Katti B, Dimidjian S, Araya R, Hollon SD, King M, Vijayakumar L, Park AL, McDaid D, Wilson T, Velleman R, Kirkwood BR, Fairburn CG. (2017)MEDLINE-indexed journal, not yet read by usLancet (London, England) · randomised controlled trial The Healthy Activity Program (HAP), a lay counsellor-delivered brief psychological treatment for severe depression, in primary care in India: a randomised controlled trial.
Background: Although structured psychological treatments are recommended as first-line interventions for depression, only a small fraction of people globally receive these treatments because of poor access in routine primary care. We assessed the effectiveness and cost-effectiveness of a brief psychological treatment (Healthy Activity Program [HAP]) for delivery by lay counsellors to patients with moderately severe to severe depression in primary health-care settings.
Methods: In this randomised controlled trial, we recruited participants aged 18-65 years scoring more than 14 on the Patient Health Questionnaire 9 (PHQ-9) indicating moderately severe to severe depression from ten primary health centres in Goa, India. Pregnant women or patients who needed urgent medical attention or were unable to communicate clearly were not eligible. Participants were randomly allocated (1:1) to enhanced usual care (EUC) alone or EUC combined with HAP in randomly sized blocks (block size four to six [two to four for men]), stratified by primary health centre and sex, and allocation was concealed with use of sequential numbered opaque envelopes. Physicians providing EUC were masked. Primary outcomes were depression symptom severity on the Beck Depression Inventory version II and remission from depression (PHQ-9 score of <10) at 3 months in the intention-to-treat population, assessed by masked field researchers. Secondary outcomes were disability, days unable to work, behavioural activation, suicidal thoughts or attempts, intimate partner violence, and resource use and costs of illness. We assessed serious adverse events in the per-protocol population. This trial is registered with the ISRCTN registry, number ISRCTN95149997.
Findings: Between Oct 28, 2013, and July 29, 2015, we enrolled and randomly allocated 495 participants (247 [50%] to the EUC plus HAP group [two of whom were subsequently excluded because of protocol violations] and 248 [50%] to the EUC alone group), of whom 466 (95%) completed the 3 month primary outcome assessment (230 [49%] in the EUC plus HAP group and 236 [51%] in the EUC alone group). Participants in the EUC plus HAP group had significantly lower symptom severity (Beck Depression Inventory version II in EUC plus HAP group 19·99 [SD 15·70] vs 27·52 [13·26] in EUC alone group; adjusted mean difference -7·57 [95% CI -10·27 to -4·86]; p<0·0001) and higher remission (147 [64%] of 230 had a PHQ-9 score of <10 in the HAP plus EUC group vs 91 [39%] of 236 in the EUC alone group; adjusted prevalence ratio 1·61 [1·34-1·93]) than did those in the EUC alone group. EUC plus HAP showed better results than did EUC alone for the secondary outcomes of disability (adjusted mean difference -2·73 [-4·39 to -1·06]; p=0·001), days out of work (-2·29 [-3·84 to -0·73]; p=0·004), intimate partner physical violence in women (0·53 [0·29-0·96]; p=0·04), behavioural activation (2·17 [1·34-3·00]; p<0·0001), and suicidal thoughts or attempts (0·61 [0·45-0·83]; p=0·001). The incremental cost per quality-adjusted life-year gained was $9333 (95% CI 3862-28 169; 2015 international dollars), with an 87% chance of being cost-effective in the study setting. Serious adverse events were infrequent and similar between groups (nine [4%] in the EUC plus HAP group vs ten [4%] in the EUC alone group; p=1·00).
Interpretation: HAP delivered by lay counsellors plus EUC was better than EUC alone was for patients with moderately severe to severe depression in routine primary care in Goa, India. HAP was readily accepted by this previously untreated population and was cost-effective in this setting. HAP could be a key strategy to reduce the treatment gap for depressive disorders, the leading mental health disorder worldwide.
Funding: Wellcome Trust.
Lancet (London, England) · randomised controlled trial · 295 citationsread the source →
Well-being interventions for individuals with diabetes: A systematic review.
In patients with diabetes, psychological well-being constructs (e.g., optimism, positive affect) have been associated with superior medical outcomes, including better glucose control and lower mortality rates. Well-being interventions may be well-suited to individuals with diabetes, as they are simple to deliver, broadly applicable across a range of psychological distress, and may help increase self-efficacy and motivation for diabetes self-care. This systematic review, completed using PRISMA guidelines, examined peer-reviewed studies indexed in PubMed, PsycINFO, and/or Scopus between database inception and October 2017 that investigated the effects of well-being interventions (e.g., positive psychology interventions, mindfulness-based interventions, resilience-based interventions) on psychological and physical health outcomes in individuals with Type 1 or Type 2 diabetes. The search yielded 34 articles (N = 1635 participants), with substantial variability in intervention type, measures used, and outcomes studied; the majority found the intervention to provide benefit. Overall, results indicate that a range of well-being interventions appear to have promise in improving health outcomes in this population, but the literature does not yet provide definitive data about which specific interventions are most effective. The variability in interventions and outcomes points to a need for further rigorous, controlled, and well-powered studies of specific interventions, with well-accepted, clinically relevant outcome measures.
Diabetes research and clinical practice · systematic review · 54 citationsread the source →
Loneliness before and during the COVID-19 pandemic: A systematic review with meta-analysis.
The COVID-19 pandemic and measures aimed at its mitigation, such as physical distancing, have been discussed as risk factors for loneliness, which increases the risk of premature mortality and mental and physical health conditions. To ascertain whether loneliness has increased since the start of the pandemic, this study aimed to narratively and statistically synthesize relevant high-quality primary studies. This systematic review with meta-analysis was registered at PROSPERO (ID CRD42021246771). Searched databases were PubMed, PsycINFO, Cochrane Library/Central Register of Controlled Trials/EMBASE/CINAHL, Web of Science, the World Health Organization (WHO) COVID-19 database, supplemented by Google Scholar and citation searching (cutoff date of the systematic search December 5, 2021). Summary data from prospective research including loneliness assessments before and during the pandemic were extracted. Of 6,850 retrieved records, 34 studies (23 longitudinal, 9 pseudolongitudinal, 2 reporting both designs) on 215,026 participants were included. Risk of bias (RoB) was estimated using the risk of bias in non-randomised studies-of interventions (ROBINS-I) tool. Standardized mean differences (SMD, Hedges' g) for continuous loneliness values and logOR for loneliness prevalence rates were calculated as pooled effect size estimators in random-effects meta-analyses. Pooling studies with longitudinal designs only (overall N = 45,734), loneliness scores (19 studies, SMD = 0.27 [95% confidence interval = 0.14-0.40], Z = 4.02, p < .001, I 2 = 98%) and prevalence rates (8 studies, logOR = 0.33 [0.04-0.62], Z = 2.25, p = .02, I 2 = 96%) increased relative to prepandemic times with small effect sizes. Results were robust with respect to studies' overall RoB, pseudolongitudinal designs, timing of prepandemic assessments, and clinical populations. The heterogeneity of effects indicates a need to further investigate risk and protective factors as the pandemic progresses to inform targeted interventions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
The American psychologist · meta-analysis · 317 citationsread the source →
Kane JM, Schooler NR, Marcy P, Correll CU, Brunette MF, Mueser KT, Rosenheck RA, Addington J, Estroff SE, Robinson J, Penn DL, Robinson DG. (2015)MEDLINE-indexed journal, not yet read by usThe Journal of clinical psychiatry · randomised controlled trial The RAISE early treatment program for first-episode psychosis: background, rationale, and study design.
Objective: The premise of the National Institute of Mental Health Recovery After an Initial Schizophrenia Episode Early Treatment Program (RAISE-ETP) is to combine state-of-the-art pharmacologic and psychosocial treatments delivered by a well-trained, multidisciplinary team in order to significantly improve the functional outcome and quality of life for first-episode psychosis patients. The study is being conducted in non-academic (ie, real-world) treatment settings, using primarily extant reimbursement mechanisms.
Method: We developed a treatment model and training program based on extensive literature review and expert consultation. Our primary aim is to compare the experimental intervention to "usual care" on quality of life. Secondary aims include comparisons on remission, recovery, and cost-effectiveness. Patients 15-40 years old with a first episode of schizophrenia, schizoaffective disorder, schizophreniform disorder, psychotic disorder not otherwise specified, or brief psychotic disorder according to DSM-IV and no more than 6 months of treatment with antipsychotic medications were eligible. Patients are followed for a minimum of 2 years, with major assessments conducted by blinded, centralized raters using live, 2-way video. We selected 34 clinical sites in 21 states and utilized cluster randomization to assign 17 sites to the experimental treatment and 17 to usual care. Enrollment began in July 2010 and ended in July 2012 with 404 subjects. The results of the trial will be published separately. The goal of the article is to present both the overall development of the intervention and the design of the clinical trial to evaluate its effectiveness.
Conclusions: We believe that we have succeeded in both designing a multimodal treatment intervention that can be delivered in real-world clinical settings and implementing a controlled clinical trial that can provide the necessary outcome data to determine its impact on the trajectory of early phase schizophrenia.
Trial registration: ClinicalTrials.gov identifier: NCT01321177.
The Journal of clinical psychiatry · randomised controlled trial · 113 citationsread the source →
Brandes JL, Kudrow D, Stark SR, O'Carroll CP, Adelman JU, O'Donnell FJ, Alexander WJ, Spruill SE, Barrett PS, Lener SE. (2007)MEDLINE-indexed journal, not yet read by usJAMA · randomised controlled trial Sumatriptan-naproxen for acute treatment of migraine: a randomized trial.
Context: Multiple pathogenic mechanisms may be involved in generating the migraine symptom complex, and multimechanism-targeted therapy may confer advantages over monotherapy.
Objective: To evaluate the efficacy and safety of a fixed-dose tablet containing sumatriptan succinate and naproxen sodium relative to efficacy and safety of each monotherapy and placebo for the acute treatment of migraine.
Design, setting, and participants: Two replicate, randomized, double-blind, single-attack, parallel-group studies conducted among 1461 (study 1) and 1495 (study 2) patients at 118 US clinical centers who were diagnosed as having migraine and received study treatment for a moderate or severe migraine attack.
Interventions: Patients were randomized in a 1:1:1:1 ratio to receive a single tablet containing sumatriptan, 85 mg, and naproxen sodium, 500 mg; sumatriptan, 85 mg (monotherapy); naproxen sodium, 500 mg (monotherapy); or placebo, to be used after onset of a migraine with moderate to severe pain.
Main outcome measures: Primary outcome measures included the percentages of patients with headache relief 2 hours after dosing, absence of photophobia, absence of phonophobia, and absence of nausea for the comparison between sumatriptan-naproxen sodium and placebo, and the percentages of patients with sustained pain-free response for the comparison between sumatriptan-naproxen sodium and each monotherapy.
Results: Sumatriptan-naproxen sodium was more effective than placebo for headache relief at 2 hours after dosing (study 1, 65% vs 28%; P<.001 and study 2, 57% vs 29%; P<.001), absence of photophobia at 2 hours (58% vs 26%; P<.001 and 50% vs 32%; P<.001), and absence of phonophobia at 2 hours (61% vs 38%; P<.001 and 56% vs 34%; P<.001). The absence of nausea 2 hours after dosing was higher with sumatriptan-naproxen sodium than placebo in study 1 (71% vs 65%; P = .007), but in study 2 rates of absence of nausea did not differ between sumatriptan-naproxen sodium and placebo (65% vs 64%; P = .71). For 2- to 24-hour sustained pain-free response, sumatriptan-naproxen sodium was superior at P<.01 (25% and 23% in studies 1 and 2, respectively) to sumatriptan monotherapy (16% and 14% in studies 1 and 2), naproxen sodium monotherapy (10% and 10% in studies 1 and 2), and placebo (8% and 7% in studies 1 and 2). The incidence of adverse events was similar between sumatriptan-naproxen sodium and sumatriptan monotherapy.
Conclusion: Sumatriptan, 85 mg, plus naproxen sodium, 500 mg, as a single tablet for acute treatment of migraine resulted in more favorable clinical benefits compared with either monotherapy, with an acceptable and well-tolerated adverse effect profile.
Trial registration: clinicaltrials.gov Identifiers: NCT00434083 (study 1); NCT00433732 (study 2).
JAMA · randomised controlled trial · 181 citationsread the source →
Interventions to increase the duration of breastfeeding in obese mothers: the Bassett Improving Breastfeeding Study.
Objective: Maternal obesity is associated with poor breastfeeding outcomes, yet no intervention has been developed to improve them. To ascertain whether increased breastfeeding support or provision of a breast pump is a feasible, effective intervention to improve breastfeeding, we enrolled obese women who intended to breastfeed in two randomized trials.
Methods: In Bassett Improving Breastfeeding Study (BIBS) 1, 40 women received targeted breastfeeding support in the hospital and via telephone or usual care. Information regarding breastfeeding was collected via telephone for 7 days after delivery and at 30 and 90 days postpartum. In BIBS 2, 34 obese mothers received a manual or electric breast pump to use for 10-14 days or no pump; data collection was similar.
Results: In both experiments, randomization failed to distribute women of differing postpartum body mass index adequately among the treatment groups. When analyses were adjusted for this, there was no difference in BIBS 1 between targeted and usual care groups and in BIBS 2 among the treatment groups in the proportion of women still breastfeeding at the times studied.
Conclusions: In future studies of obese women, stratified randomization may be necessary. Further development of interventions to help obese women achieve optimal breastfeeding outcomes is required.
Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine · randomised controlled trial · 62 citationsread the source →
Body composition and appetite: fat-free mass (but not fat mass or BMI) is positively associated with self-determined meal size and daily energy intake in humans.
The idea of body weight regulation implies that a biological mechanism exerts control over energy expenditure and food intake. This is a central tenet of energy homeostasis. However, the source and identity of the controlling mechanism have not been identified, although it is often presumed to be some long-acting signal related to body fat, such as leptin. Using a comprehensive experimental platform, we have investigated the relationship between biological and behavioural variables in two separate studies over a 12-week intervention period in obese adults (total n 92). All variables have been measured objectively and with a similar degree of scientific control and precision, including anthropometric factors, body composition, RMR and accumulative energy consumed at individual meals across the whole day. Results showed that meal size and daily energy intake (EI) were significantly correlated with fat-free mass (FFM, P values < 0·02-0·05) but not with fat mass (FM) or BMI (P values 0·11-0·45) (study 1, n 58). In study 2 (n 34), FFM (but not FM or BMI) predicted meal size and daily EI under two distinct dietary conditions (high-fat and low-fat). These data appear to indicate that, under these circumstances, some signal associated with lean mass (but not FM) exerts a determining effect over self-selected food consumption. This signal may be postulated to interact with a separate class of signals generated by FM. This finding may have implications for investigations of the molecular control of food intake and body weight and for the management of obesity.
The British journal of nutrition · randomised controlled trial · 151 citationsread the source →
Griffin SJ, Simmons RK, Williams KM, Prevost AT, Hardeman W, Grant J, Whittle F, Boase S, Hobbis I, Brage S, Westgate K, Fanshawe T, Sutton S, Wareham NJ, Kinmonth AL, ADDITION-Plus study team. (2011)MEDLINE-indexed journal, not yet read by usBMC public health · randomised controlled trial Protocol for the ADDITION-Plus study: a randomised controlled trial of an individually-tailored behaviour change intervention among people with recently diagnosed type 2 diabetes under intensive UK general practice care.
Background: The increasing prevalence of type 2 diabetes poses both clinical and public health challenges. Cost-effective approaches to prevent progression of the disease in primary care are needed. Evidence suggests that intensive multifactorial interventions including medication and behaviour change can significantly reduce cardiovascular morbidity and mortality among patients with established type 2 diabetes, and that patient education in self-management can improve short-term outcomes. However, existing studies cannot isolate the effects of behavioural interventions promoting self-care from other aspects of intensive primary care management. The ADDITION-Plus trial was designed to address these issues among recently diagnosed patients in primary care over one year.
Methods/design: ADDITION-Plus is an explanatory randomised controlled trial of a facilitator-led, theory-based behaviour change intervention tailored to individuals with recently diagnosed type 2 diabetes. 34 practices in the East Anglia region participated. 478 patients with diabetes were individually randomised to receive (i) intensive treatment alone (n = 239), or (ii) intensive treatment plus the facilitator-led individual behaviour change intervention (n = 239). Facilitators taught patients key skills to facilitate change and maintenance of key behaviours (physical activity, dietary change, medication adherence and smoking), including goal setting, action planning, self-monitoring and building habits. The intervention was delivered over one year at the participant's surgery and included a one-hour introductory meeting followed by six 30-minute meetings and four brief telephone calls. Primary endpoints are physical activity energy expenditure (assessed by individually calibrated heart rate monitoring and movement sensing), change in objectively measured dietary intake (plasma vitamin C), medication adherence (plasma drug levels), and smoking status (plasma cotinine levels) at one year. We will undertake an intention-to-treat analysis of the effect of the intervention on these measures, an assessment of cost-effectiveness, and analyse predictors of behaviour change in the cohort.
Discussion: The ADDITION-Plus trial will establish the medium-term effectiveness and cost-effectiveness of adding an externally facilitated intervention tailored to support change in multiple behaviours among intensively-treated individuals with recently diagnosed type 2 diabetes in primary care. Results will inform policy recommendations concerning the management of patients early in the course of diabetes. Findings will also improve understanding of the factors influencing change in multiple behaviours, and their association with health outcomes.
BMC public health · randomised controlled trial · 21 citationsread the source →
Postpartum anxiety and maternal-infant health outcomes.
Objective: Postpartum anxiety screening does not typically occur, despite changes in life roles and responsibility after childbirth. We sought to determine the prevalence of postpartum anxiety during the maternity hospitalization and its associations with maternal and child outcomes. We further aimed to compare correlates of anxiety with correlates of depression.
Methods: For a randomized controlled trial of mothers with "well" newborns ≥34 weeks' gestation comparing 2 post-hospital discharge care models, mothers completed baseline in-person interviews during the postpartum stay and telephone surveys at 2 weeks, 2 months, and 6 months to assess health care use, breastfeeding duration, anxiety, and depression. All participants intended to breastfeed. State anxiety scores ≥40 on the State Trait Anxiety Inventory (STAI) and depression scores ≥12 on the Edinburgh Postnatal Depression Survey (EPDS) were considered positive.
Results: A total of 192 (17%) of 1123 participating mothers had a positive baseline STAI; 62 (6%) had a positive EPDS. Primiparity was associated with a positive STAI (20% vs 15%, P = .02), but not a positive EPDS (4% vs 7%, P = .05). Positive STAI scores were associated with cesarean delivery (22% vs 15%, P = .001), reduced duration of breastfeeding (P = .003), and increased maternal, but not infant total unplanned health care utilization within 2 weeks of delivery (P = .001). Positive STAI scores occurred more frequently than positive EPDS scores at each assessment through 6 months postpartum.
Conclusions: Postpartum state anxiety is a common, acute phenomenon during the maternity hospitalization that is associated with increased maternal health care utilization after discharge and reduced breastfeeding duration. State anxiety screening during the postpartum stay could improve these outcomes.
Pediatrics · randomised controlled trial · 132 citationsread the source →
Self-Compassion as a prospective predictor of PTSD symptom severity among trauma-exposed U.S. Iraq and Afghanistan war veterans.
U.S. combat veterans of the Iraq and Afghanistan wars have elevated rates of posttraumatic stress disorder (PTSD) compared to the general population. Self-compassion, characterized by self-kindness, a sense of common humanity when faced with suffering, and mindful awareness of suffering, is a potentially modifiable factor implicated in the development and maintenance of PTSD. We examined the concurrent and prospective relationship between self-compassion and PTSD symptom severity after accounting for level of combat exposure and baseline PTSD severity in 115 Iraq and Afghanistan war veterans exposed to 1 or more traumatic events during deployment. PTSD symptoms were assessed using the Clinician Administered PTSD Scale for DSM-IV (CAPS-IV) at baseline and 12 months (n =101). Self-compassion and combat exposure were assessed at baseline via self-report. Self-compassion was associated with baseline PTSD symptoms after accounting for combat exposure (β = -.59; p < .001; ΔR(2) = .34; f(2) = .67; large effect) and predicted 12-month PTSD symptom severity after accounting for combat exposure and baseline PTSD severity (β = -.24; p = .008; ΔR(2) = .03; f(2) = .08; small effect). Findings suggest that interventions that increase self-compassion may be beneficial for treating chronic PTSD symptoms among some Iraq and Afghanistan war veterans.
Journal of traumatic stress · 41 citationsread the source →
The Indirect Effect of Parental Intolerance of Uncertainty on Perinatal Mental Health via Mindfulness During COVID-19.
Objectives: The COVID-19 pandemic is associated with mental health difficulties, especially during pregnancy and early postpartum. Intolerance of uncertainty (IU) and reduced capacity for mindfulness-a protective factor for child-bearers-may be particularly relevant factors driving mental health problems given the unpredictable nature of the pandemic. The current study aims to shed light on modifiable paths to perinatal psychological distress by testing whether there is an indirect effect of IU on psychological symptoms through a perceived reduction in mindfulness during the pandemic.
Methods: Pregnant individuals (67%, n = 133) and new mothers within 6 months postpartum (33%, n = 66) participated in a cross-sectional online survey assessing IU, current and retrospective pre-pandemic mindfulness (FFMQ), and psychological symptoms (anxiety, depression, somatization; BSI). Perceived change in mindfulness was captured by including retrospective mindfulness as a covariate in the PROCESS macro used for analyses.
Results: Tests of the direct association between mindfulness, IU, and psychological symptoms showed significant effects of IU (b = 0.46, SE = 0.064; p < .001) and perceived decrease in mindfulness during the pandemic (b = - 0.72, SE = 0.08, p < .001) on psychological symptoms (R 2 = .21-.34; F[2, 197] = 51.13-52.81, p < .001). The indirect effect of IU on symptoms via perceived decrease in mindfulness during the pandemic (b = 0.13, SE = 0.043, 95%CI [.060, .226]) was significant (R 2 = .41, F[3, 195] = 45.08, p < .001).
Conclusions: Results suggest that mothers who are less able to tolerate uncertainty experience more psychological symptoms, in part due to perceived reduction in mindfulness during the pandemic. Future research should examine whether IU is a screening risk marker and target for mindfulness-based interventions to improve maternal well-being and family outcomes.
Mindfulness · 16 citationsread the source →
Hand Posturing Is a Nonverbal Indicator of Catastrophic Thinking for Finger, Hand, or Wrist Injury.
Background: Prior research documents that greater psychologic distress (anxiety/depression) and less effective coping strategies (catastrophic thinking, kinesophobia) are associated with greater pain intensity and greater limitations. Recognition and acknowledgment of verbal and nonverbal indicators of psychologic factors might raise opportunities for improved psychologic health. There is evidence that specific patient words and phrases indicate greater catastrophic thinking. This study tested proposed nonverbal indicators (such as flexion of the wrist during attempted finger flexion or extension of uninjured fingers as the stiff and painful finger is flexed) for their association with catastrophic thinking.
Questions/purposes: (1) Do patients with specific protective hand postures during physical examination have greater pain interference (limitation of activity in response to nociception), limitations, symptoms of depression, catastrophic thinking (protectiveness, preparation for the worst), and kinesophobia (fear of movement)? (2) Do greater numbers of protective hand postures correlate with worse scores on these measures?
Methods: Between October 2014 and September 2016, 156 adult patients with stiff or painful fingers within 2 months after sustaining a finger, hand, or wrist injury were invited to participate in this study. Six patients chose not to participate as a result of time constraints and one patient was excluded as a result of inconsistent scoring of a possible hand posture, leaving 149 patients for analysis. We asked all patients to complete a set of questionnaires and a sociodemographic survey. We used Patient Reported Outcomes Measurement Information System (PROMIS) Depression, Upper Extremity Physical Function, and Pain Interference computer adaptive test (CAT) questionnaires. We used the Abbreviated Pain Catastrophizing Scale (PCS-4) to measure catastrophic thinking in response to nociception. Finally, we used the Tampa Scale of Kinesophobia (TSK) to assess fear of movement. The occurrence of protective hand postures during the physical examination was noted by both the physician and researcher. For uncertainty or disagreement, a video of the physical examination was recorded and a group decision was made.
Results: Patients with one or more protective hand postures did not score higher on the PROMIS Pain Interference CAT (hand posture: 59 [56-64]; no posture: 59 [54-63]; difference of medians: 0; p = 0.273), Physical Function CAT (32 ± 8 versus 34 ± 8; mean difference: 2 [confidence interval {CI}, -0.5 to 5]; p = 0.107), nor the Depression CAT (48 [41-55] versus 48 [42-53]; difference of medians: 0; p = 0.662). However, having at least one hand posture was associated with a higher degree of catastrophic thinking (PCS scores: 13 [6-26] versus 10 [3-16]; difference of medians: 3; p = 0.0104) and a higher level of kinesophobia (TSK: 40 ± 6 versus 38 ± 6; mean difference: -2 [CI, -4 to -1]; p = 0.0420). Greater catastrophic thinking was associated with a greater number of protective hand postures on average (rho: 0.20, p = 0.0138).
Conclusions: Protective hand postures and (based on prior research) specific words and phrases are associated with catastrophic thinking and kinesophobia, less effective coping strategies that hinder recovery. Surgeons can learn to recognize these signs and begin to treat catastrophic thinking and kinesophobia starting with compassion, empathy, and patience and be prepared to add formal support (such as cognitive-behavioral therapy) to help facilitate recovery.
Level of evidence: Level III, diagnostic study.
Clinical orthopaedics and related research · cohort or longitudinal · 35 citationsread the source →
Comorbidity and associated severity of borderline personality disorder and physical health conditions in a nationally representative sample.
Objective: To investigate the comorbidity and severity of borderline personality disorder and physical health conditions in a nationally representative sample. Despite the recent trend of examining the relationship between physical and mental health, there has been limited research examining the association of physical health conditions and personality disorders, in particular, borderline personality disorder.
Methods: The National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) Wave 2 (n = 34,653; cumulative response rate, 70.2%; age, ≥20 years) was used in the current study. The Alcohol Use Disorder and Associated Disabilities Interview Schedule-Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition was used to assess mental disorders, and self-reports were used to assess physical health conditions. Multiple logistic regression models examined the comorbidity of physical health conditions with borderline personality disorder and associated suicide attempts.
Results: After adjusting for sociodemographic variables, common Axis I mental disorders, and Axis II personality disorders, the presence of borderline personality disorder was significantly associated with arteriosclerosis or hypertension, hepatic disease, cardiovascular disease, gastrointestinal disease, arthritis, venereal disease, and "any assessed medical condition" (adjusted odds ratios, range 1.46-2.80). In the most stringent adjusted model, diabetes, stroke, and obesity were not associated with borderline personality disorder. Furthermore, a greater likelihood of suicide attempts was associated with cardiovascular disease, venereal disease, and "any assessed medical condition" with comorbid borderline personality disorder than borderline personality disorder alone.
Conclusion: Careful screening and treatment of physical health conditions among people with borderline personality disorder are warranted.
Psychosomatic medicine · cohort or longitudinal · 137 citationsread the source →
Welch V, Tugwell P, Petticrew M, de Montigny J, Ueffing E, Kristjansson B, McGowan J, Benkhalti Jandu M, Wells GA, Brand K, Smylie J. (2010)MEDLINE-indexed journal, not yet read by usThe Cochrane database of systematic reviews · systematic review How effects on health equity are assessed in systematic reviews of interventions.
Background: Enhancing health equity has now achieved international political importance with endorsement from the World Health Assembly in 2009. The failure of systematic reviews to consider effects on health equity is cited by decision-makers as a limitation to their ability to inform policy and program decisions.
Objectives: To systematically review methods to assess effects on health equity in systematic reviews of effectiveness.
Search strategy: We searched the following databases up to July 2 2010: MEDLINE, PsychINFO, the Cochrane Methodology Register, CINAHL, Education Resources Information Center, Education Abstracts, Criminal Justice Abstracts, Index to Legal Periodicals, PAIS International, Social Services Abstracts, Sociological Abstracts, Digital Dissertations and the Health Technology Assessment Database. We searched SCOPUS to identify articles that cited any of the included studies on October 7 2010.
Selection criteria: We included empirical studies of cohorts of systematic reviews that assessed methods for measuring effects on health inequalities.
Data collection and analysis: Data were extracted using a pre-tested form by two independent reviewers. Risk of bias was appraised for included studies according to the potential for bias in selection and detection of systematic reviews.
Main results: Thirty-four methodological studies were included. The methods used by these included studies were: 1) Targeted approaches (n=22); 2) gap approaches (n=12) and gradient approach (n=1). Gender or sex was assessed in eight out of 34 studies, socioeconomic status in ten studies, race/ethnicity in seven studies, age in seven studies, low and middle income countries in 14 studies, and two studies assessed multiple factors across health inequity may exist. Only three studies provided a definition of health equity. Four methodological approaches to assessing effects on health equity were identified: 1) descriptive assessment of reporting and analysis in systematic reviews (all 34 studies used a type of descriptive method); 2) descriptive assessment of reporting and analysis in original trials (12/34 studies); 3) analytic approaches (10/34 studies); and 4) applicability assessment (11/34 studies). Both analytic and applicability approaches were not reported transparently nor in sufficient detail to judge their credibility.
Authors' conclusions: There is a need for improvement in conceptual clarity about the definition of health equity, describing sufficient detail about analytic approaches (including subgroup analyses) and transparent reporting of judgments required for applicability assessments in order to assess and report effects on health equity in systematic reviews.
The Cochrane database of systematic reviews · systematic review · 48 citationsread the source →
Harald M. Stauss (2003)MEDLINE-indexed journal, not yet read by usAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology · review Heart rate variability
IN FOCUSHeart rate variabilityHarald M. StaussHarald M. StaussDepartment of Exercise Science, University of Iowa, Iowa City, Iowa 52242Published Online:01 Nov 2003https://doi.org/10.1152/ajpregu.00452.2003MoreSectionsPDF (59 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations the rhythm of the heart has not only fascinated cardiologists but also inspired poets and musicians. Indeed, the periodic beat of the heart was used to define the speed of music. In music notation, the traditional Italian term "moderato" originally referred to one beat of the measure per walking pace (76-80 paces/min) or heartbeat (∼72 beats/min). The use of the heartbeat to define the speed of music may imply that the periodicity of the beat of the heart is very constant. However, this is not necessarily the case. In fact, loss of heart rate variability can indicate severe cardiovascular diseases and reliably predict poor outcome of such conditions (18, 22, 27, 47a). This In Focus article reviews sources of heart rate variability, its role as a prognostic marker for cardiovascular diseases, and its application in estimation of cardiac autonomic nervous system activity. All of these topics have been addressed intensely in articles published in the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology during the last two years. In healthy subjects, the sinoatrial node located at the posterior wall of the right atrium initiates each beat of the heart. Due to the unstable membrane potential of the myocytes located in this region, action potentials are generated periodically at a fairly constant frequency. This relatively constant frequency generated by the autorhythmicity of the sinoatrial node is modulated by many factors that add variability to the heart rate signal at different frequencies. According to the Task Force of The European Society of Cardiology and The North American Society of Pacing and Electrophysiology (47a) these frequencies are classified into 1) ultra-low frequencies (ULF; >5-h cycle length) that include the circadian rhythm (6, 9, 34, 54); 2) very low frequencies (VLF; >25-s cycle length) that are supposed to be affected by temperature regulation (1, 7, 34, 52, 54) and humoral systems (9, 36); 3) low frequencies (LF; >6-s cycle length in humans) that are sensitive to changes in cardiac sympathetic (and presumably parasympathetic) nerve activity (27, 30); and 4) high frequencies (HF; 2.5- to 6.0-s cycle length in humans) that are synchronized to the respiratory rhythm (5) and are primarily modulated by cardiac parasympathetic innervation (38).The most prominent oscillation in the ULF band of the heart rate spectrum is the circadian rhythm. The autonomic nervous system contributes significantly to circadian heart rate variability. Using long-term recordings in conscious rabbits, Barrett et al. (6) demonstrated a strong circadian rhythm in heart rate, mean arterial blood pressure, renal blood flow, and renal sympathetic nerve activity. The importance of this study is that it clearly demonstrates that sympathetic nerve discharges exhibit a strong circadian rhythmicity. The paraventricular nucleus of the hypothalamus (PVN) appears to play a central role in mediating the circadian rhythm of autonomic nervous system activity. First, GABAergic and glutamatergic neurons project from the suprachiasmatic nuclei of the hypothalamus (SCN) to spinal-projecting neurons of the PVN (12). The SCN is the major central oscillator that triggers the day/night cycle. It receives photic input from the retina (47) and drives many neuroendocrine, metabolic, autonomic, and behavioral circadian rhythms (14, 16, 21, 31, 35, 44, 46, 50). In addition, microinjections of the inhibitory neurotransmitter GABA into the PVN of anesthetized rats elicit dose-dependent decreases in renal sympathetic nerve activity, whereas bicuculline (a GABA antagonist) increases renal sympathetic nerve activity (56). Second, from the PVN, neurons project to the nucleus of the solitary tract (that integrates inputs from the baroreceptors), the nucleus ambiguus (origin of preganglionic parasympathetic neurons to the heart), the rostroventrolateral medulla (location of sympathetic premotor neurons), and the intermediolateral cell column of the thoracolumbar spinal cord (location of preganglionic sympathetic neurons). Thus PVN neurons can modulate autonomic nervous system activity by sending inputs to major sites of autonomic nervous system regulation. As an example, a pivotal role of the PVN for sympathoexcitation during parturition was recently demonstrated in sheep. The increase in sympathetic nerve activity that accompanies birth in maternal animals was prevented by stereotactic lesioning of the PVN (43). Taken together, a major component of the circadian heart rate variability is elicited by diurnal fluctuations in autonomic nervous system activity, generated by corresponding fluctuations of neuronal activity within the PVN, which depend on circadian inputs originating from the SCN.It has been suggested that thermoregulation affects VLF heart rate variability (10, 26). Cooling the heart causes bradycardia, a mechanism used in heart surgeries. Conversely, fever is known to increase heart rate. Raising body core temperature from 36.0 to 36.6°C caused an increase in heart rate by almost 40 beats/min in male subjects (1), whereas acutely reducing ambient temperature from thermoneutral conditions (35°C) to 29, 23, and 17°C, reduced heart rate from 400 to 250 beats/min in 8-day-old rats (7). In addition, lowering temperature in the isolated working rat heart from 37 to 31°C reduced heart rate from 332 to 215 beats/min and markedly increased heart rate variability (28), indicating that parts of the temperature effects on heart rate and heart rate variability are independent from the autonomic nervous system. In contrast to the tachycardia that accompanies acute elevations in temperature, chronically raising ambient temperature in adult rodents from a standard housing temperature of 21-23°C to thermoneutral conditions (29-30°C) reduced heart rate by roughly 50 beats/min in rats (34) and by 200-300 beats/min in mice (54). The authors of these articles (34, 54) suggested that standard housing temperatures are associated with cold stress that causes parallel activation of brown adipose tissue, cardiac, and vasomotor sympathetic drives that elicits nonshivering thermogenesis and tonically elevates heart rate and arterial blood pressure. These and other studies indicate that both direct effects of temperature on pacemaker activity of the sinus node (28) and indirect effects mediated via the autonomic nervous system (11, 25, 51, 55) mediate temperature effects on heart rate and heart rate variability. Thus fluctuation in temperature is an important source of heart rate variability that should not be underestimated. In a more recent study, this was taken into account by core body temperature correction of heart rate variability (3).Endocrine factors affecting heart rate variability include thyroxine, reproductive hormones, the renin-angiotensin system, steroids, and others. Chronic subcutaneous infusion of angiotensin II in rats markedly increased blood pressure and heart rate variability, expressed as standard deviation (9). In contrast, chronic corticosterone treatment is likely to reduce baroreflex-mediated heart rate variability, because baroreceptor-heart rate (39) and baroreceptor-renal sympathetic nerve activity reflex sensitivity (41) were blunted in chronically corticosterone-treated rats. Furthermore, an interaction between angiotensin II and glucocorticoids was recently described. Intracerebro-ventricular microinjections of angiotensin II AT1 receptor antagonists caused marked decreases in mean blood pressure and heart rate in rats chronically treated with corticosterone but not in control animals (40). This interaction is likely to take place in the central nervous system, because peripheral angiotensin II AT1 receptor blockade did not alter the effects of betamethasone treatment on blood pressure, heart rate, and baroreceptor-heart rate reflex sensitivity in newborn lambs (42).Adenosine is a substance less known to affect heart rate variability. It is produced locally in the heart (53) and binds to A1-adenosinergic receptors, which are among the earliest expressed G protein-coupled receptors in the heart (36). The A1-adenosinergic agonist N6-cyclopentyladenosine dose dependently reduced heart rate in murine embryos, whereas 1,3-dipropyl-8-cyclopentylxanthine, an A1-adenosinergic antagonist, increased heart rate (36). Adenosine also exerts central nervous system effects in various brain areas (15, 20). Microinjections of adenosine into the nucleus of the solitary tract of awake rats caused dose-dependent changes in heart rate: low doses (0.01 nmol) produced a bradycardic response, whereas high doses (2.5-5.0 nmol) elicited a tachycardic response (15). Thus adenosine may indeed be involved in the regulation of heart rate and modulate heart rate variability via local cardiac and central nervous system effects. It has been proposed that the intrinsic cardiac nervous system plays an active role in regulating cardiac function (4, 37, 45, 57). This nervous system consists of sympathetic and parasympathetic neurons and interconnecting local circuits (37). Neurons in the canine right atrial ganglionated plexus (RAGP) spontaneously generate activity even after chronic cardiac autonomic denervation (45). Right atrial neurons in patients undergoing coronary artery bypass surgery generated spontaneous activity that was unrelated to the cardiac cycle but sensitive to changes in systemic arterial pressure, indicating that these neurons receive pressure-sensitive sensory inputs (4). In addition, it has been suggested that substance P acts as a neuromodulator and neurotransmitter in intracardiac ganglia of the guinea pig, modulates the response to vagal inputs, and triggers action potentials at the site of parasympathetic ganglia independent of acetylcholine (57). Furthermore, the right atrial (RAGP) and the posterior atrial ganglionated plexus (PAGP) appear to have different functions. Ablation of the PAGP reduced vagally mediated bradycardia by 26%, whereas RAGP ablation completely abolished this response. Inhibition of sympathetically mediated tachycardia by vagal stimulation was attenuated by ablation of either plexus (37). Thus parasympathetic efferent neurons are primarily located in the RAGP, whereas prejunctional parasympathetic-sympathetic interactions also involve neurons within the PAGP (37). The spontaneous activity of neurons in the intrinsic cardiac nervous system, even after cardiac denervation (45), suggests an active role of this system in regulating heart rate. However, the impact of the intrinsic cardiac nervous system on heart rate variability remains to be elucidated. The importance of the autonomic nervous system for heart rate variability in humans becomes apparent in patients following cardiac transplantation, in whom heart rate variability is markedly reduced (49). Although reinnervation is possible after months and years, initially transplanted hearts can be considered to be denervated. Thus the reduced heart rate variability in cardiac transplanted patients (49) underlines the importance of an intact autonomic innervation for spontaneously occurring heart rate variability. A major component of the chronotropic effect of the autonomic nervous system is linked to cAMP. Intracellular cAMP increases the inward current of Na+ (funny current, If), which determines the rate of the slow diastolic depolarization that precedes each action potential. The activity of adenylate cyclase and thus intracellular cAMP levels are increased by stimulation of sympathetic β1-adrenergic receptors and decreased (via a Gi protein) by stimulation of parasympathetic muscarinic receptors. Thus cardiac sympathetic innervation increases the rate of the slow diastolic depolarization and accelerates heart rate, while cardiac parasympathetic innervation elicits opposite effects. Interestingly, parasympathetic-mediated changes in heart rate occur much faster than sympathetic-mediated effects on heart rate (27, 30, 47a). As a result, cardiac sympathetic nervous system activity can only affect LF components of heart rate variability, whereas the parasympathetic nervous system can also modulate HF components. A hitherto unsolved question in this context is if the rapid heart rate response to parasympathetic stimulation compared with the slow effect of sympathetic inputs is due to 1) different kinetics of β1-adrenergic vs. muscarinic receptors, 2) different kinetics of adenylate cyclase vs. phosphodiesterase, the enzyme that cleaves cAMP, or 3) fast parasympathetic-mediated opening of KACh channels (via muscarinic receptors and a GK protein). Support for the latter possibility comes from experiments in the rabbit sinoatrial node that demonstrated that activation of KACh channels contributes to the initial slowing of heart rate as a result of vagal stimulation (8).On the basis of the different frequency response characteristics of sympathetic and parasympathetic modulation of heart rate, frequency analysis of heart rate variability is often used as a tool to determine "autonomic balance" or sympathetic and parasympathetic nervous system activity (27, 47a). As an example, the wavelet transform was recently used to determine cardiac autonomic responses to reperfusion in patients with thrombolysis after coronary thrombosis. Depending on the location of the infarct, marked alterations in LF or HF spectral power of heart rate or in the LF/HF ratio was observed in all successful reperfusions (48).The HF component corresponds to the frequency of respiration and is driven by the vagus as indicated by the strong respiratory pattern of cardiac vagal motoneurons in the nucleus ambiguus (38). The LF component has been ascribed to sympathetic modulation of cardiac pacemaker activity, because a variety of studies demonstrated that acute interventions that increase sympathetic nervous system activity, such as orthostatic perturbations (17, 19, 33), mental stress (32), or handgrip exercise (13, 24) increases LF spectral power of heart rate (27, 30). In addition to acute perturbations of cardiac sympathetic nerve activity, feedback oscillations generated by the baroreceptor reflex also appear to contribute to LF spectral power of heart rate as it was demonstrated that sinoaortic denervation markedly reduces the LF component (27, 30). Despite the strong modulation of heart rate by the autonomic nervous system, the LF and HF spectral components of heart rate variability may not always be very reliable markers for cardiac sympathetic and parasympathetic "tone" (30). In a recent study, muscle sympathetic nerve activity was recorded together with heart rate variability during application of lower body negative pressure that is known to increase muscle sympathetic nerve activity (17, 33). At higher levels of lower body negative pressure (-15 mmHg), both muscle sympathetic nerve activity and relative LF spectral power of heart rate increased significantly, whereas HF spectral power decreased (17). These findings suggest that LF spectral power reflects cardiac sympathetic "tone." However, no correlation within subjects was found between changes in LF/HF ratio and muscle sympathetic nerve activity (17). Thus heart rate variability does not reliably reflect the sympathetic response to orthostatic stress. Respiration-related fluctuation of heart rate (respiratory sinus arrhythmia) is probably the most often investigated component of heart rate variability, as it is believed that this component reflects respiration-driven vagal modulation of sinus arrhythmia (27). In a recent study, Rentero et al. (38) recorded the electrical activity from cardiac vagal motoneurons in the nucleus ambiguus. Firing of these neurons was modulated by the central respiratory cycle. This and other studies support the view that respiratory sinus arrhythmia is generated by central coupling of the respiratory oscillator with autonomic centers in the brain stem. However, a mechanical cardiopulmonary coupling as a source of respiration-related heart rate variability has also been suggested (5). The Bainbridge reflex causes a tachycardia in response to hypervolemia. This reflex is initiated by atrial mechanoreceptors and uses efferent sympathetic and parasympathetic pathways to modulate heart rate in response to changes in central venous pressure (23). Thus respiratory changes in central blood volume cause corresponding respiratory fluctuations in cardiac autonomic nervous system activity via the Bainbridge reflex. Only the parasympathetic component of the efferent pathway of the reflex can contribute to respiratory sinus arrhythmia, because sympathetic actions on heart rate are too damped to follow the respiratory frequency. The gain and phase of the transfer function between respiratory changes in lung volume and R-R intervals of the ECG were calculated in human subjects during graded changes in central blood volume (5). At the respiratory frequency, the phase was -180 degree, indicating that an inspiratory increase in central blood volume was associated with a decrease in R-R interval (increase in heart rate). Furthermore, the gain of the transfer function at the respiratory frequency steadily increased with increasing central volumes (except at the highest volume). Both of these findings confirm the presence of the Bainbridge reflex in humans (5). Thus, in addition to the central coupling of respiratory oscillators with cardiovascular centers, the Bainbridge reflex may contribute to respiration-related heart rate variability by mechanical cardiopulmonary coupling. There is general agreement that low heart rate variability is an unfavorable prognostic marker for cardiovascular diseases, such as diabetic autonomic neuropathy, hypertension, myocardial infarction, and heart failure (18, 22, 27, 29, 47a). Heart rate variability (variance of R-R intervals) was reduced in patients with mild hypertension (29) compared with normal values (1,134 ± 202 vs. 3,466 ± 1,018 ms2) provided by the Task Force (47a). In the rat model of myocardial infarction-induced congestive heart failure, Francis and colleagues (18) reported loss of spontaneous heart rate variability 6 wk after coronary artery ligation. Interestingly, reduced heart rate variability was also observed in a rat model of depression that is based on chronic (4 wk) mild stress application (22). Because depression is an independent risk factor for coronary artery disease, this finding may realistically model a human disease process. The reduction in heart rate variability was abolished by β-adrenergic receptor blockade, indicating that the reduced heart rate variability in this model of depression is related to elevated cardiac sympathetic tone (22).In summary, heart rate variability is generated by multiple factors not exclusively limited to the autonomic nervous system. Specific frequency components of heart rate variability mirror acute perturbations of the autonomic nervous system but do not always reflect autonomic nervous system activity. Simple statistics of heart rate variability, such as the standard deviation of R-R intervals in the ECG, can reliably predict the prognosis of cardiovascular diseases.I thank Dr. R. McAllen for critically reviewing the manuscript. References 1 Aoki K, Stephens DP, and Johnson JM. Diurnal variation in cutaneous vasodilator and vasoconstrictor systems during heat stress. Am J Physiol Regul Integr Comp Physiol 281: R591-R595, 2001.Link | ISI | Google Scholar3 Aoyagi N, Ohashi K, and Yamamoto Y. Frequency characteristics of long-term heart rate variability during constant-routine protocol. Am J Physiol Regul Integr Comp Physiol 285: R171-R176, 2003.Link | ISI | Google Scholar4 Arora RC, Hirsch GM, Johnson Hirsch K, Hancock Friesen C, and Armour JA. Function of human intrinsic cardiac neurons in situ. Am J Physiol Regul Integr Comp Physiol 280: R1736-R1740, 2001.Link | ISI | Google Scholar5 Barbieri R, Triedman JK, and Saul JP. Heart rate control and mechanical cardiopulmonary coupling to assess central volume: a systems analysis. Am J Physiol Regul Integr Comp Physiol 283: R1210-R1220, 2002.Link | ISI | Google Scholar6 Barrett CJ, Navakatikyan MA, and Malpas SC. Long-term control of renal blood flow: what is the role of the renal nerves? Am J Physiol Regul Integr Comp Physiol 280: R1534-R1545, 2001.Link | ISI | Google Scholar7 Blumberg MS, Knoot TG, and Kirby RF. Neural and hormonal control of arterial pressure during cold exposure in un-anesthetized week-old rats. Am J Physiol Regul Integr Comp Physiol 281: R1514-R1521, 2001.Link | ISI | Google Scholar8 Boyett MR, Kodama I, Honjo H, Arai A, Suzuki R, and Toyama J. Ionic basis of the chronotropic effect of acetylcholine on the rabbit sinoatrial node. Cardiovasc Res 29: 867-878, 1995.Crossref | PubMed | ISI | Google Scholar9 Braga and of on fluctuations and changes in blood pressure. Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google and elicited of heart rate variability. J Physiol | ISI | Google and modulation of sympathetic nerve activity to muscle in Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google and and GABA mediate suprachiasmatic nucleus inputs to spinal-projecting paraventricular Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and is not associated with of the exercise reflex in Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google C, and Y. The effect of on the circadian control of human core body temperature is Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and of adenosine receptors in the does not affect the in awake rats. Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google JK, A, and circadian and during two Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and sympathetic nerve and heart rate spectral effects of lower body negative pressure. Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google Francis Johnson and of heart failure after myocardial in the Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google A, and of lower body pressure on muscle sympathetic nerve activity response to Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and Adenosine initial depression of in the rat in Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google R, and and circadian phase in a diurnal the Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and Johnson alterations and autonomic in an model of Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google MA, and The interaction of the Bainbridge and in the conscious Res | ISI | Google A, and handgrip exercise arterial control of sympathetic in Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and nerve regulation to is in rats. Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and in heart rate variability. J Physiol | ISI | Google and function and cardiovascular interactions and Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and interval variability in isolated working rat hearts at various conditions and Res | PubMed | Google A, A, and and autonomic of in patients with mild Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google Malpas SC. Neural on cardiovascular and Am J Physiol Heart Physiol 2002.Link | ISI | Google and thermoregulation in and rats in a Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and effects on reflex responses to mental stress in Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and reflex during orthostatic in Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and and responses to and are in rats. Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and and in a by cycle. Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and of humoral heart rate regulation in the Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google Armour and within the intrinsic cardiac nervous system contribute to chronotropic regulation. Am J Physiol Regul Integr Comp Physiol 285: 2003.Link | ISI | Google Rentero N, A, and McAllen of cardiac vagal motoneurons in rat nucleus ambiguus. Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and modulate control of heart rate in conscious rats. Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google and central actions of angiotensin to increase arterial pressure. Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and modulate control of renal sympathetic nerve activity. Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and modulation of cardiovascular and autonomic function in role of Am J Physiol Regul Integr Comp Physiol 280: 2001.Link | ISI | Google and Inhibition of sympathetic responses at birth in by of the paraventricular Am J Physiol Regul Integr Comp Physiol 283: 2002.Link | ISI | Google and JP. pattern of during acute and chronic in conscious adult rats. Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google Armour and of chronic cardiac on of canine intracardiac neurons in Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and levels and circadian rhythm of activity in the a model of Am J Physiol Regul Integr Comp Physiol 281: 2001.Link | ISI | Google and nerve response of suprachiasmatic nucleus and Am J Physiol Regul Integr Comp Physiol 2002.Link | ISI | Google
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · review · 309 citationsread the source →
Raising Spanish Children With an Antisocial Tendency: Do We Know What the Optimal Parenting Style Is?
Families can play an essential role in preventing violent and antisocial behaviors, which are considered a significant public health issue. However, some studies argue that most children are antisocial only during adolescence, and even teenagers can mimic antisocial behavior in ways that are normative and well-adjusted. This study analyzed patterns of competence and adjustment in young adults with and without an antisocial tendency during adolescence from authoritative (characterized by warmth and strictness), authoritarian (strictness but not warmth), indulgent (warmth but not strictness), and neglectful (neither warmth nor strictness) families. Emergent research has indicated that in a European context, the indulgent parenting style is optimal. Offspring's competence and adjustment were captured through self-esteem (academic and family), psychosocial development (self-competence and empathy), and low emotional maladjustment (nervousness and hostility). Participants consisted of a community sample of 489 Spanish young adults, 191 men (39.1%) and 298 women (60.9%), aged 18 to 34 years old. The design was a 4 × 2 × 2 × 2 MANOVA (parenting style × antisocial tendency × sex × age). Analysis of main effects showed that youths with an antisocial tendency have less self-esteem and psychosocial development, but more emotional maladjustment. Regardless of the parenting style, an antisocial tendency during adolescence is consistently associated with worse adjustment in young adults. Both the authoritative and indulgent parenting styles are consistently associated with better outcomes (higher self-esteem and psychosocial development, and lower emotional maladjustment) than the authoritarian and neglectful parenting styles. However, there are interactions between the parenting style and the antisocial tendency. For young adults without an antisocial tendency, only indulgent parenting is associated with less emotional maladjustment. These results support the idea that in Europe the indulgent parenting style performs better than the authoritative style, but only when raising adolescents without an antisocial tendency. For young adults with an antisocial tendency, indulgent and authoritative parenting are equally optimal for all the studied outcomes.
Journal of interpersonal violence · 36 citationsread the source →
The Silent Crisis: Loneliness in Older Adults-A Critical Review of Impacts, Strategies and Path Forward.
Background: Loneliness, distinct from social isolation, is a subjective sense of social disconnection exacerbating a public health crisis among older adults. Affecting ~33% of community-dwelling individuals aged 50-80 years post-COVID-19, it rivals smoking in mortality risk and drives cognitive, cardiovascular, and mental health declines. This review synthesises evidence to inform clinical strategies.
Methods: A critical review of per-reviewed meta-analyses, RCTs, and prospective cohorts literature (2019-2025) was conducted for adults aged 50 years and above. Studies were selected using validated loneliness or social isolation measures, with quality appraised via AMSTAR-2, Cochrane RoB 2, and Newcastle-Ottawa Scale; 34 studies met eligibility criteria from an initial yield of 1,847 records.
Results: Prevalence of loneliness stands at 29% isolation by 2024, highest among those with poor health (53%-75%), unemployment (52%), solitary living, and ages 50-64. Loneliness elevates all-cause mortality (32%), dementia (50%-59%), cardiovascular events (29%-32%), depression (40%), and anxiety (35%). Mechanisms include increased inflammation (↑CRP, IL-6), HPA dysregulation, immune compromise, hippocampal atrophy, and behavioural lapses. Interventions like CBT/reminiscence therapy, multicomponent programs, animal therapy, exercise, and digital platforms have been shown to reduce loneliness, though primary care implementation lags due to screening/referral barriers. Tools such as the UCLA Loneliness Scale enable feasible assessment.
Conclusions: Loneliness as a geriatric syndrome demands mandated screening, provider education, and reimbursement reforms. Coordinated healthcare-community efforts could avert substantial morbidity/mortality, addressing gaps in long-term outcomes and cost-effectiveness research.
Scandinavian journal of caring sciences · reviewread the source →
Research Summit III Proceedings on Dosing in Children With an Injured Brain or Cerebral Palsy: Executive Summary
Children with brain injuries or cerebral palsy (CP) comprise a large percentage of pediatric clients served by physical therapists. There is no consensus on what the basic parameters should be for different treatment protocols. A very important parameter of intervention that is pivotal for treatment efficacy is dosing. Dosing decisions are complex. To date, the minimum doses for changing structure and function, activity, and participation in children with various disabilities are unknown. This article describes the process and outcomes of a research summit with the goals of: (1) fostering a critical debate that would result in recommendations for the development of large-scale, second-generation research proposals to address thresholds for effective dosing of interventions for children with brain injuries or CP and (2) enhancing the research capacity of pediatric physical therapists through collaborative research networks. The summit brought together an interdisciplinary cadre of researchers (physical therapists, basic and clinical scientists), representatives from funding agencies, and consumers to an intensive 2.5-day think tank. The summit targeted questions of treatment dosage related to 3 areas: practice and neuroplasticity, structure-behavior connections, and clinical trial design. The consensus was that the intervention must demonstrate some evidence of effectiveness before optimal dosing can be investigated. Constraint-induced movement therapy (CIMT) is used as an example of an intervention that has demonstrated effectiveness and that requires dosing-related research. Summit results, including factors that merit special consideration and recommendations for future dose-related studies, are highlighted. Physical therapy is an important service for children with physical disabilities, particularly those with an injured brain resulting in neuromotor impairments and functional limitations.1 These children typically have multiple health complications that often result in complex functional limitations and require extensive health care, education, and vocational training. The costs of interventions result in substantial financial and social challenges for families and society.2 Although physical therapists frequently provide continuous interventions for children with physical disabilities, including CP,3 there remains limited empirical support for these services.4 Dosing represents a critical and pressing aspect of intervention that is central for treatment efficacy. In this article, dose is defined as the frequency, intensity, time, and type of an intervention.5Frequency refers to how often, such as the number of sessions for a given intervention per day, week, or month. Intensity refers to how hard the child works within the intervention session and is recorded as the number of repetitions per minute, day, or week or amount of work (eg, 75% of maximal heart rate). Time refers to the duration of the intervention. Type refers to the kind of intervention and can be focused at any of the dimensions of the International Classification of Functioning, Disability and Health (ICF): body functions and structures, activity, or participation.6 Within types, variation exists. For example, task practice can vary in the type of behavioral shaping (ie, structured versus unstructured training) and amount of feedback or reward. Type of intervention is central to the discussion because determining the “salient” or “active” ingredient of an intervention strategy is intimately related to the question of dosing. What is “it” that should be dosed? Intervention strategies also involve interactions with biomechanical, neuromuscular, and psychological elements of a child's behavior, necessitating insight into the mechanism leading to a change in behavior. Consequently, the nature of optimal dosage can be expected to vary with different types of interventions. Intervention-related dosing is a source of disagreement among service providers, policy makers, insurers, and researchers, whose recent findings show the potential for high dosing intervention to be the catalyst for positive intervention outcomes.7 The cost related to high dosing is one impediment to implementation. Another is uncertainty about the minimal dose that is effective and sufficient. Some of the most promising targeted interventions that seek to promote plastic changes in the brain and muscle, such as training on a treadmill,8 CIMT,9–12 and strength training,13,14 have used varying doses. The findings from these studies have highlighted a complex dosing knowledge gap, namely, a disconnect between structural and behavioral changes, where changes that are seen at one dimension of the ICF are not always incorporated into others. The disconnect between structural and behavioral changes15 provides a compelling argument for revisiting hypotheses regarding mechanisms for adaptive motor learning and for a critical examination of dosing at the cellular, structural, activity, and participation levels. Collectively, these findings and the question of dosing suggest that scientific exploration of the effect of dosing in pediatric physical therapy and its interaction with other aspects of intervention will be a challenging enterprise. The findings suggest that for the field of pediatric physical therapy or rehabilitation to move forward, the dosing question will require an interdisciplinary coordinated effort, using sound conceptual frameworks and a systems perspective. A research summit offers a plausible launching pad for promoting an interdisciplinary coordinated effort and addressing some of these complex questions related to dosing. In this article, we define a research summit as a think-tank mechanism whereby different parties can contribute to the development of well-crafted research programs or action plans designed to move science on a specific topic to the next level. For the past 9 years, the Section on Pediatrics of the American Physical Therapy Association (APTA) has used interdisciplinary research summits developed by the first author and colleagues to foster development of large-scale research proposals on a topic of great importance to pediatric practice and simultaneously increase the research capacity of pediatric physical therapists. The results have shown that, with creative and meaningful collaborations, short-term intensive meetings can help increase the numbers of pediatric therapists with postprofessional doctoral training who are successful in securing funding to conduct research on a targeted topic that advances practice. The first research summit (RS I), in 2004, addressed physical fitness in children with CP and secondary complications.16 To date, this summit has resulted in 71 publications, 36 presentations, and 29 funded grants, 6 of which were from the National Institutes of Health (NIH), totaling more than $2 million. The second summit (RS II), in 2007, focused on early intervention for children with or at risk for disabilities. It has resulted in 34 publications, 34 submitted grants, and 14 funded grants, 2 from NIH and 2 from the National Institute on Disability and Rehabilitation Research (NIDRR), totaling more than $900,000. Many of the grant proposals have involved collaboration between several physical therapists and non–physical therapist summit participants. The current research summit (RS III) was modeled after these 2 highly successful summits to direct research attention to the critical issue of dosing of interventions for children with an injured brain. The goals of RS III were: (1) to foster a critical debate that would result in recommendations for the development of large-scale, second-generation research proposals to address thresholds for effective dosing for children with an injured brain or CP and (2) to enhance the research capacity of pediatric physical therapists by facilitating collaborations, information exchange (cross-fertilization), and networking among physical therapists, other researchers (basic, neuroscience, movement, and clinical scientists), consumers, and funding agencies in the area of dosing of interventions for children with an injured brain or CP. The summit was held in Alexandria, Virginia, in October 2011. This article summarizes the highlights of the summit deliberations, factors that merited special consideration regarding dosing interventions, and recommendations for dosing studies that will help advance this area. The emphasis was on 3 body structures known to be affected by injury to the brain, rehabilitation, and dosing: muscle, bone, and brain.17–19 We used the ICF6 as an organizing framework. In addition to discussing issues related to direct intervention strategies, we also emphasized patient and family education and addressed the importance of activity, participation, and family dynamics. We illustrate the need for sequential and systematic studies of dosing and the salient features of intervention upon which dosing parameters should be based by summarizing the findings from an intervention with known efficacy (CIMT) that still requires dosing-related research. A total of 48 individuals (see Appendix) participated in the summit. The planning committee, with the help of other researchers and representatives of funding agencies, identified 12 scientists with relevant expertise in neuroscience, movement science, pediatrics, muscle and exercise physiology, imaging, bone health, neurology, occupational therapy, and statistics. Also invited were representatives from APTA, funding agencies and foundations, and 4 consumers. The committee identified 2 physical therapy researchers with established research agendas and a history of federal funding (Dr Stuart Binder-Macleod and Dr Diane Damiano) to serve as facilitators. Details of participants are listed in Table 1. Characteristics of Research Summit Participants Characteristics of Research Summit Participants Participation by additional pediatric physical therapists was through an application process. An independent review committee selected 17 physical therapist participants who met one or more criteria: history of funded research in the area of interventions or measurement for children with neurological disorders, currently conducting research (funded or unfunded) in this area, or postprofessional physical therapist students who are mentored by researchers conducting clinical trials or intervention research. All participants submitted a 3-page biographical sketch and a 2- to 4-page position or perspective paper that focused on the subject of dosing and expectations from the summit and highlighted their own research. The biographical sketches and position or perspective papers were disseminated to all participants before the summit to maximize information sharing and help participants become familiar with one another's research and expertise, thereby facilitating networking and communication during the summit. The planning committee applied for and received funding from APTA's Section on Pediatrics, the National Institute of Child Health and Human Development, and the National Institute of Neurologic Disorders and Stroke to support the cost of the summit. The RS III was a 3-day conference designed to systematically address the current state of clinical research in the area of intervention dosing and to create research networks and goals. The first day focused on information exchange and identification of knowledge gaps. The second day built on the information presented on the first day by formulating scientific questions and considering research designs to explore dosing. The day was to the development of action and research The the of the summit. and of Research Summit The and and of 2 by representatives from funding agencies, and or by participants. The first address was by Dr an established in clinical The goals of this address were to the and to of the in the area of intervention dosing. A of 2 family and 2 individuals with CP the second All were from the area and in of and The goals for the were to the of on the of clinical practice and the of or for the were to provide a catalyst for and and of the of dosing and its and potential research by all participants were to define the of by the to the and of research in which participants are exchange information on current and past research and potential for and strategies for The goals of these were: (1) to promote the of (2) to research to research questions that would to research and to promote discussion of research action and researchers were with based on of or There were a total of 3 discussion of at (1) practice and or muscle and in children with injured or (2) structural and behavioral changes and and clinical These 3 were by the planning committee to be the for the of intervention dosing and emphasized muscle, bone, and brain. Participants were for the first 2 sessions and to for the session based on research and potential of the topic of were presented to the large for an discussion and consensus for future collaborative research The the to the and at the and of the summit the to and of the planning committee served as to the of the goals of the to the summit goals and to the and for In the that we and from and specific aspects that merited critical consideration on the topic of and recommendations for research by the summit participants. from the of bone and brain are used to of research that were in the summit. The consensus from the first discussion that the and by research participants and representatives from funding agencies was that dosing is a Participants that the minimal and optimal dosage of interventions would on the neuromuscular, and of the children the nature of the intervention the type of functional goals to be and and A by Dr in address was to the salient of the intervention that to changes in motor and to be repetitions of movement per of intervention per day, per week, total number of and amount of intervention. the of of clinical questions of of of and total of intervention are related as are their The was that of these would require its own of studies or that the interaction of these should be in effectiveness research. Another by the information presented by the of consumers, was to the interaction of dose with other interventions used in pediatric rehabilitation, often within or The that because dosing need to be for a systematic exploration of dosing would be a research from the first the need to the effectiveness or mechanism of for specific types of interventions within and and must seek to address the question of some changes are and some are studies also must address and factors to with plastic changes in the bone, and of the of the bone of children with CP or injured a for considering specific and Dosing research questions bone in children with CP should exercise that the in the are most to with and are more is between The of be based on a child's of and change as a child to the exercise the repetitions with more between exercise sessions to maximize the of dosing will be important has a at which factors that have the potential to enhance and the potential of a such as and or also need to be In the requires a duration a minimum of 3 to a to exercise with other systems such as and muscle dose-related questions were to be different on the of the of questions are presented in Table of Research What is the minimal and optimal dose of for important change in is the change and What is the optimal dose of physical to increase muscle the and increase participation in with and What are the minimal and optimal doses of training to and functional in children with CP What is the minimal and optimal dose of for important change in is the change and What is the optimal dose of physical to increase muscle the and increase participation in with and What are the minimal and optimal doses of training to and functional in children with CP movement therapy, Classification of Research What is the minimal and optimal dose of for important change in is the change and What is the optimal dose of physical to increase muscle the and increase participation in with and What are the minimal and optimal doses of training to and functional in children with CP What is the minimal and optimal dose of for important change in is the change and What is the optimal dose of physical to increase muscle the and increase participation in with and What are the minimal and optimal doses of training to and functional in children with CP movement therapy, Classification from the discussion based on from on structure-behavior (1) that current intervention studies have outcomes that not always to (2) that changes to be and that the results through intervention are specific (ie, what of these that the high doses of for children with CP has not to in functional of the affected in muscle structure have with limited changes in studies have demonstrated in capacity in children who received training and in those who received 2 of research questions identified by the that, would help to to dosing questions and structure-behavior to the need to structure-behavior was the consideration that outcomes in the are the also must be to the intervention in the not the not outcomes must of and change has The was that studies of intervention dosing must the minimum and optimal doses that can all of the ICF that are and to The also highlighted the importance of using and of patient and in addition to of intervention and The of that ICF and the of the of with and cost were from the clinical with knowledge of the mechanisms brain or in children with dose-related research also must involve of of body structure and that changes in and The of of at the of the ICF was These be with from recent advances in such as and The of is at the participation level. The outcomes such as adaptive which that to the child's level. have developed and to physical the of the which was developed by NIH to provide a of highly measurement of health for and social The of and with children with CP has the of several recent The discussion session on clinical trials and other research designs identified 3 of (1) minimal dose and optimal dose for important (2) optimal dose to and functional in children with CP Classification and which the optimal dose of physical to the to increase muscle and bone and bone and the between and outcomes in studies or effectiveness research (ie, what works for and and the potential and of an A of the extensive on dose-related and as to these 3 are The also as recommendations for future dose-related research trials and studies, including effectiveness were as strategies for a critical of to address the dosing questions and challenges should and interventions that have the potential to meaningful change for the child and family and that are and and effective dose must involve a sequential of related hypotheses and of effectiveness in a meaningful should by studies to the minimal dose for or the The sequential should require identification of the salient of the intervention that to changes in of the participants and questions of frequency, intensity, and of a type of intervention which are related as as including such as child For the intervention to be at the of an intervention must be which would require at one after more would have would need to strategies such as a which is a to of to to is the of intervention This refers to changes at different during an intervention to information on the at what different outcomes were and intervention that to This that dosing-related studies will require designs than Although all that would be to optimal was that other factors the dose would the would need to be as and factors will or the must be and in factors must of and family The that the should be on all to interventions that have the potential to meaningful change for the child and family and that are and in to interventions is in to that are and the of the of will be by the among these factors and the factors The question for researchers should What aspects of the and with intervention doses to The about of therapy, as children and on the importance of the of therapy to the child's current such as or dose-related studies will require of designs and or conceptual The for an of in research and training and that such should be early in the process of grant or The the need to an minimal or of outcomes for studies with such as those with the of or such as the NIH and consideration and exploration as outcomes for dosing are one to the effectiveness of interventions, the of outcomes was as of great importance in addressing dosing the consensus was that the intervention must demonstrate some evidence of effectiveness before optimal dosing should be investigated. An example of an intervention that has demonstrated effectiveness and that requires dosing-related research is with This intervention also was selected as a future area by one during the to address the question of a minimal dose and optimal dose for important What is a of the in Table that dosing be from the various other parameters of intervention that with of the Therapy (CIMT) and to A of more than children or of or intensive therapy show that of training resulted in or of at than of training. Classification of Functioning, Disability and of the Therapy (CIMT) and to A of more than children or of or intensive therapy show that of training resulted in or of at than of training. Classification of Functioning, Disability and children with CP and to were given 6 of intervention per day functional task practice with shaping (ie, training with positive for in children with CP and 2 to 6 years, was that 3 per day, for results that were research that the duration of training from to the number of of training per day at 3 not the of the affected by was per day in of the Another early research developed in demonstrated motor learning after extensive In this and with the more affected were It should be that there studies of pediatric all of these studies the intervention with a or and at dosing that be a of than the type of intervention the development of intensive therapy trials of and have shown that demonstrated in and of the as a in of the during a suggest the importance of of practice show that of training resulted in and of at than of training. This example highlights the importance of research to the specific and their to The of this summit was to foster a critical debate that would result in recommendations for the development of large-scale research proposals to address dosing for children with injured or CP. presented in the that the summit was successful in fostering a critical debate on this topic and recommendations for research on this The next for intervention dosing are in Table 4 and what RS III physical therapists, and different can to that intervention dosing be a research and to foster on a for Research on movement therapy, for Research and Physical Therapy International Research for Research on movement therapy, for Research and Physical Therapy International Research The second of enhancing the research capacity of pediatric physical therapists by facilitating and networking was as by how the for the Some of the on to and 2 interdisciplinary planning that were funded by the Section on Pediatrics in physical therapists served as in we the of this summit to increase with Summit participants will be 2 about submitted grants, funded and that resulted from this summit. This research summit was the first and in a systematic and of dosing questions and an interdisciplinary second-generation dose-related research. The consensus is that an intervention must demonstrate effectiveness before dose-related studies can be In this article, we the process and of the highlighted several factors that merit special consideration for dosing studies, and recommendations for clinical trials and other strategies to advance research on this The recommendations are to second-generation intervention research questions and targeted interdisciplinary foster of rehabilitation at all of the and the of children with an injured brain or CP. Section on Pediatrics Research Summit The Research Summit III and for Children an or was by the American Physical Therapy Association (APTA) Section on Pediatrics, the National Institutes of National Institute of Child Health and Human and the National Institute of Disorders and Stroke October Alexandria, at the of Research Summit III are Section on Pediatrics Research Summit The Research Summit III and for Children an or was by the American Physical Therapy Association (APTA) Section on Pediatrics, the National Institutes of National Institute of Child Health and Human and the National Institute of Disorders and Stroke October Alexandria, at the of Research Summit III are
Physical Therapy · 69 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 →
Garvey WT, Mechanick JI, Brett EM, Garber AJ, Hurley DL, Jastreboff AM, Nadolsky K, Pessah-Pollack R, Plodkowski R, Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. (2016)MEDLINE-indexed journal, not yet read by usEndocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · guideline AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY COMPREHENSIVE CLINICAL PRACTICE GUIDELINES FOR MEDICAL CARE OF PATIENTS WITH OBESITY.
Objective: Development of these guidelines is mandated by the American Association of Clinical Endocrinologists (AACE) Board of Directors and the American College of Endocrinology (ACE) Board of Trustees and adheres to published AACE protocols for the standardized production of clinical practice guidelines (CPGs).
Methods: Recommendations are based on diligent review of clinical evidence with transparent incorporation of subjective factors.
Results: There are 9 broad clinical questions with 123 recommendation numbers that include 160 specific statements (85 [53.1%] strong [Grade A]; 48 [30.0%] intermediate [Grade B], and 11 [6.9%] weak [Grade C], with 16 [10.0%] based on expert opinion [Grade D]) that build a comprehensive medical care plan for obesity. There were 133 (83.1%) statements based on strong (best evidence level [BEL] 1 = 79 [49.4%]) or intermediate (BEL 2 = 54 [33.7%]) levels of scientific substantiation. There were 34 (23.6%) evidence-based recommendation grades (Grades A-C = 144) that were adjusted based on subjective factors. Among the 1,790 reference citations used in this CPG, 524 (29.3%) were based on strong (evidence level [EL] 1), 605 (33.8%) were based on intermediate (EL 2), and 308 (17.2%) were based on weak (EL 3) scientific studies, with 353 (19.7%) based on reviews and opinions (EL 4).
Conclusion: The final recommendations recognize that obesity is a complex, adiposity-based chronic disease, where management targets both weight-related complications and adiposity to improve overall health and quality of life. The detailed evidence-based recommendations allow for nuanced clinical decision-making that addresses real-world medical care of patients with obesity, including screening, diagnosis, evaluation, selection of therapy, treatment goals, and individualization of care. The goal is to facilitate high-quality care of patients with obesity and provide a rational, scientific approach to management that optimizes health outcomes and safety.
Abbreviations: A1C = hemoglobin A1c AACE = American Association of Clinical Endocrinologists ACE = American College of Endocrinology ACSM = American College of Sports Medicine ADA = American Diabetes Association ADAPT = Arthritis, Diet, and Activity Promotion Trial ADHD = attention-deficit hyperactivity disorder AHA = American Heart Association AHEAD = Action for Health in Diabetes AHI = apnea-hypopnea index ALT = alanine aminotransferase AMA = American Medical Association ARB = angiotensin receptor blocker ART = assisted reproductive technology AUC = area under the curve BDI = Beck Depression Inventory BED = binge eating disorder BEL = best evidence level BLOOM = Behavioral Modification and Lorcaserin for Overweight and Obesity Management BLOSSOM = Behavioral Modification and Lorcaserin Second Study for Obesity Management BMI = body mass index BP = blood pressure C-SSRS = Columbia Suicidality Severity Rating Scale CAD = coronary artery disease CARDIA = Coronary Artery Risk Development in Young Adults CBT = cognitive behavioral therapy CCO = Consensus Conference on Obesity CHF = congestive heart failure CHO = carbohydrate CI = confidence interval COR-I = Contrave Obesity Research I CPG = clinical practice guideline CV = cardiovascular CVD = cardiovascular disease DASH = Dietary Approaches to Stop Hypertension DBP = diastolic blood pressure DEXA = dual-energy X-ray absorptiometry DPP = Diabetes Prevention Program DSE = diabetes support and education EL = evidence level ED = erectile dysfunction ER = extended release EWL = excess weight loss FDA = Food and Drug Administration FDG = 18F-fluorodeoxyglucose GABA = gamma-aminobutyric acid GERD = gastroesophageal reflux disease GI = gastrointestinal GLP-1 = glucagon-like peptide 1 HADS = Hospital Anxiety and Depression Scale HDL-c = high-density lipoprotein cholesterol HR = hazard ratio HTN = hypertension HUNT = Nord-Trøndelag Health Study ICSI = intracytoplasmic sperm injection IFG = impaired fasting glucose IGT = impaired glucose tolerance ILI = intensive lifestyle intervention IVF = in vitro fertilization LAGB = laparoscopic adjustable gastric banding LDL-c = low-density lipoprotein cholesterol LES = lower esophageal sphincter LSG = laparoscopic sleeve gastrectomy LV = left ventricle LVH = left ventricular hypertrophy LVBG = laparoscopic vertical banded gastroplasty MACE = major adverse cardiovascular events MAOI = monoamine oxidase inhibitor MI = myocardial infarction MNRCT = meta-analysis of non-randomized prospective or case-controlled trials MRI = magnetic resonance imaging MUFA = monounsaturated fatty acid NAFLD = nonalcoholic fatty liver disease NASH = nonalcoholic steatohepatitis NES = night eating syndrome NHANES = National Health and Nutrition Examination Surveys NHLBI = National Heart, Lung, and Blood Institute NHS = Nurses' Health Study NICE = National Institute for Health and Care Excellence OA = osteoarthritis OGTT = oral glucose tolerance test OR = odds ratio OSA = obstructive sleep apnea PHQ-9 = Patient Health Questionnaire PCOS = polycystic ovary syndrome PCP = primary care physician POMC = pro-opiomelanocortin POWER = Practice-Based Opportunities for Weight Reduction PPI = proton pump inhibitor PRIDE = Program to Reduce Incontinence by Diet and Exercise PSA = prostate specific antigen QOL = quality of life RA = receptor agonist RCT = randomized controlled trial ROC = receiver operator characteristic RR = relative risk RYGB = Roux-en-Y gastric bypass SAD = sagittal abdominal diameter SBP = systolic blood pressure SCOUT = Sibutramine Cardiovascular Outcome Trial SG = sleeve gastrectomy SHBG = sex hormonebinding globulin SIEDY = Structured Interview on Erectile Dysfunction SNRI = serotonin-norepinephrine reuptake inhibitors SOS = Swedish Obese Subjects SS = surveillance study SSRI = selective serotonin reuptake inhibitors STORM = Sibutramine Trial on Obesity Reduction and Maintenance TCA = tricyclic antidepressant TONE = Trial of Nonpharmacologic Intervention in the Elderly TOS = The Obesity Society T2DM = type 2 diabetes mellitus UKPDS = United Kingdom Prospective Diabetes Study U.S = United States VAT = visceral adipose tissue VLDL = very low-density lipoprotein WC = waist circumference WHO = World Health Organization WHR = waist-hip ratio WHtR = waist-to-height ratio WMD = weighted mean difference WOMAC = Western Ontario and McMaster Universities osteoarthritis index XENDOS = XEnical in the Prevention of Diabetes in Obese Subjects.
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · guideline · 1258 citationsread the source →
Bohren MA, Vogel JP, Hunter EC, Lutsiv O, Makh SK, Souza JP, Aguiar C, Saraiva Coneglian F, Diniz AL, Tunçalp Ö, Javadi D, Oladapo OT, Khosla R, Hindin MJ, Gülmezoglu AM. (2015)MEDLINE-indexed journal, not yet read by usPLoS medicine · systematic review The Mistreatment of Women during Childbirth in Health Facilities Globally: A Mixed-Methods Systematic Review.
Background: Despite growing recognition of neglectful, abusive, and disrespectful treatment of women during childbirth in health facilities, there is no consensus at a global level on how these occurrences are defined and measured. This mixed-methods systematic review aims to synthesize qualitative and quantitative evidence on the mistreatment of women during childbirth in health facilities to inform the development of an evidence-based typology of the phenomenon.
Methods and findings: We searched PubMed, CINAHL, and Embase databases and grey literature using a predetermined search strategy to identify qualitative, quantitative, and mixed-methods studies on the mistreatment of women during childbirth across all geographical and income-level settings. We used a thematic synthesis approach to synthesize the qualitative evidence and assessed the confidence in the qualitative review findings using the CERQual approach. In total, 65 studies were included from 34 countries. Qualitative findings were organized under seven domains: (1) physical abuse, (2) sexual abuse, (3) verbal abuse, (4) stigma and discrimination, (5) failure to meet professional standards of care, (6) poor rapport between women and providers, and (7) health system conditions and constraints. Due to high heterogeneity of the quantitative data, we were unable to conduct a meta-analysis; instead, we present descriptions of study characteristics, outcome measures, and results. Additional themes identified in the quantitative studies are integrated into the typology.
Conclusions: This systematic review presents a comprehensive, evidence-based typology of the mistreatment of women during childbirth in health facilities, and demonstrates that mistreatment can occur at the level of interaction between the woman and provider, as well as through systemic failures at the health facility and health system levels. We propose this typology be adopted to describe the phenomenon and be used to develop measurement tools and inform future research, programs, and interventions.
PLoS medicine · systematic review · 950 citationsread the source →
The melatonin receptor agonist is effective for free-running type circadian rhythm sleep disorder: case report on two sighted patients.
Along with urbanization of the living environment, the number of patients with circadian rhythm sleep disorder (CRSD) has been increasing. There are several treatment candidates for CRSD, such as light therapy, drugs (melatonin and vitamin B12), and sleep hygiene education. However, successful treatment method has not been established. In free-running type (FRT) CRSD, the endogenous circadian rhythm cannot be entrained to the 24-h light-dark cycle, resulting in free running on a cycle 0.5-2.5 h longer than the 24-h period. This condition is relatively common in blind individuals and is unusual in sighted individuals. Here we report two sighted patients with FRT, successfully treated with a melatonin receptor agonist, ramelteon. Patient 1 (36-year-old female) had suffered from FRT for nearly 4 months after resigning her job. She was given sleep hygiene education together with ramelteon at first and the free-running cycle stopped after treatment day 15. Triazolam was added from the day 25 to promote earlier sleep onset. And the sleep-wake schedule was normalized by the day 34. Patient 2 (33-year-old male) had suffered from FRT for nearly 8 months after starting to take a leave of absence from his job. He was given sleep hygiene education and was treated with ramelteon and methylcobalamin. His sleep-wake schedule was normalized from the first treatment day. By the combined treatment with ramelteon, both patients have maintained favorable sleep-wake schedules. The agonist action of ramelteon at the melatonin 2 receptor may have primarily contributed to the cessation of the free-running cycle in these patients.
The Tohoku journal of experimental medicine · case report · 11 citationsread the source →
Comparison of the dipeptidyl peptidase-4 inhibitor vildagliptin and the sulphonylurea gliclazide in combination with metformin, in Muslim patients with type 2 diabetes mellitus fasting during Ramadan: results of the VECTOR study.
Objective: To compare the incidence of hypoglycaemic events (HEs) in a real-world setting in Muslim patients with type 2 diabetes mellitus fasting during Ramadan.
Research design and methods: We performed a ≤16-week prospective, non-interventional, two-cohort study. Data were collected 1-6 weeks before and ≤6 weeks after fasting. Patients were enrolled who had been receiving vildagliptin (50 mg twice daily) or sulphonylurea (SU) as add-on to metformin at least 4 weeks prior to fasting.
Main outcome measures: The primary efficacy endpoint was incidence of HEs during the Ramadan fast. Changes in glycated haemoglobin (HbA(1c)) and body weight, as well as adherence to treatment, were also assessed.
Results: Seventy-two patients were enrolled (vildagliptin, n = 30; SU, n = 41; no treatment, n = 1), of whom 23 (76.7%) and 36 (87.8%), respectively, completed the study. With vildagliptin, there were no HEs or severe HEs, compared with 34 HEs (15 patients, 41.7%) and one severe (grade 2) HE with SU. The mean between-group difference in the proportion who experienced at least one HE was -41.7% (95%CI -57.8%, -25.6%), p = 0.0002. Vildagliptin lowered mean HbA(1c) from 7.6% (SD 0.9%) at baseline to 7.2% (SD 0.7%) post-Ramadan, whereas SU had no effect (7.2% [SD 0.6%] vs 7.3% [SD 0.7%]; mean between-group difference -0.5% [95% CI -0.9%, -0.1%], p = 0.0262). The mean number of missed doses was markedly lower with vildagliptin (0.2 [SD 0.8] vs 7.6 [SD 14.9]; mean between-group difference -7.4 [95% CI -13.7, -1.20] doses; p = 0.0204). Body weight remained unchanged in both groups.
Conclusion: Vildagliptin caused no hypoglycaemia, was well adhered to and improved HbA(1c), making it a suitable treatment option for managing fasting. Study limitations are the sample size and the lack of diet and exercise data. When extrapolated to the global Muslim population with a similar clinical background, these findings could have considerable public health and clinical implications.
Current medical research and opinion · cohort or longitudinal · 56 citationsread the source →
Sexual victimisation, peer victimisation, and mental health outcomes among adolescents in Burkina Faso: a prospective cohort study.
Background: Sexual victimisation and peer victimisation are pervasive and increase risk for mental illness. Longitudinal studies that compare their unique and cumulative effects are scarce and have been done predominantly in high-income countries. The aims of this study were to examine the prevalence, prospective associations, and gender differences in sexual and peer victimisation and mental health in a low-income, African setting.
Methods: In this prospective cohort study, data were obtained from the 2017 ARISE Adolescent Health Study, a population-representative, two-wave, prospective study of adolescents (aged 12-20 years) from Burkina Faso. A random sample of adolescents was drawn from ten villages, selected to capture the five main ethnic groups, and from one of the seven sectors of Nouna town, Burkina Faso, at two timepoints: Nov 12 to Dec 27, 2017, and Nov 15 to Dec 20, 2018. Standardised interviews were conducted in French or a local language by trained researchers. We measured victimisation exposure as sexual victimisation, peer victimisation, and polyvictimisation, using lifetime frequency of exposure, and we measured mental health symptoms and disorders using the Kutcher Adolescent Depression Scale, the Primary Care Post-Traumatic Stress Disorder screen IV and 5, and a question on lifetime self-harm and number of incidents in the past year. We calculated prevalence of victimisation and mental health symptoms and disorders at the two timepoints, and we used lifetime victimisation at the first timepoint to predict mental health at the second timepoint using logistic and negative binomial regressions. Gender differences were examined using interaction terms.
Findings: Of 2544 eligible adolescents, 1644 participated at time 1 and 1291 participated at time 2. The final sample with data at both timepoints included 1160 adolescents aged 12-20 years (mean 15·1, SE 0·2), of whom 469 (40·4%) were girls and 691 (59·6%) were boys. The majority ethnic group was Dafin (626 [39·1%]), followed by Bwaba (327 [20·5%]), Mossi (289 [16·0%]), Samo (206 [13·0%]), Peulh (166 [9·7%]), and other (30 [1·6%]). After survey weight adjustment, sexual victimisation (weighted percentages, time 1, 256 [13·8%] of 1620; time 2, 93 [7·2%] of 1264) and peer victimisation (weighted percentages, time 1, 453 [29·9%] of 1620; time 2, 272 [21·9%] of 1264) were common, whereas polyvictimisation was more rare (weighted percentages, time 1, 116 [6·6%] of 1620; time 2, 76 [5·7%] of 1264). Longitudinally, sexual victimisation was associated with probable clinical disorder (adjusted odds ratio 2·59, 95% CI 1·15-5·84), depressive symptoms (adjusted incidence rate ratio [aIRR] 1·39, 95% CI 1·12-1·72), and symptoms of post-traumatic stress disorder (aIRR 2·34, 1·31-4·16). Peer victimisation was associated with symptoms of post-traumatic stress disorder (aIRR 1·89, 1·13-3·17) and polyvictimisation was associated with depressive symptoms (aIRR 1·34, 1·01-1·77). Girls reported more sexual victimisation (weighted percentages, 130 [17·3%] of 681 vs 126 [11·4%] of 939), boys reported more peer victimisation (weighted percentages, 290 [33·1%] of 939 vs 163 [25·2%] of 681), and there was a significant interaction between lifetime victimisation and gender for probable clinical disorder (F [degrees of freedom 7, sample 376] 2·16; p=0·030).
Interpretation: Sexual and peer victimisation were common in the study setting and increased risk for mental health problems. Adolescent girls who have been sexually victimised are especially at risk of mental health problems. Interventions targeting sexual and peer violence in low-income settings are needed.
Funding: Alexander von Humboldt Foundation, the Wellcome Trust, Fondation Botnar, and Harvard TH Chan School of Public Health.
The lancet. Psychiatry · 9 citationsread the source →
Gong J, Cheung S, Fasso-Opie A, Galvin O, Moniz LS, Earle D, Durham T, Menzo J, Li N, Duffy S, Dolgin J, Shearman MS, Fiorani C, Banhazi J, Daly A. (2021)MEDLINE-indexed journal, not yet read by usClinical ophthalmology (Auckland, N.Z.) The Impact of Inherited Retinal Diseases in the United States of America (US) and Canada from a Cost-of-Illness Perspective.
Objective: To estimate the annual cost of inherited retinal diseases (IRDs) in the United States of America (US) and Canada from a societal perspective - including costs to the health system, individual and family productivity costs, lost wellbeing and other societal economic costs - by setting and payer. Findings will inform the need for policy action to mitigate the impact of IRDs.
Methods: The costs of IRDs were estimated using a cost-of-illness methodology, based on the prevalence of IRDs in each country. Intangible costs of reduced wellbeing were also estimated using disability-adjusted life years which were then converted to monetary values using the value of a statistical life.
Results: Using base prevalence rates, total costs attributable to IRDs in the US were estimated to range between US$13,414.0 and US$31,797.4 million in 2019, comprising both economic costs (between US$4,982 and US$11,753.9 million; 37% of total costs) and wellbeing costs (between US$8,431.7 and US$20,043.6 million; 63%). Total costs attributable to IRDs in Canada were estimated to range between CAN$1637.8 and CAN$6687.5 million in 2019, comprising both economic costs (between CAN$566.6 and CAN$2,305.7 million; 34%) and wellbeing costs (between CAN$1,071.4 and CAN$4,381.9 million; 66% of total costs).
Conclusion: The impact of IRDs in the US and Canada is substantial when considering both economic costs and reduced wellbeing. The wellbeing costs due to IRDs in the US and Canada are considerable, accounting for over 60% of total costs. Vision loss from IRDs often manifests in childhood, meaning some people live with vision impairment and blindness for their whole lives. Further research into current and emerging cost-effective therapies and interventions is required given the substantial economic burden faced by those living with vision loss.
Clinical ophthalmology (Auckland, N.Z.) · 60 citationsread the source →
Koster EB, Baars EW, Delnoij DM. (2016)MEDLINE-indexed journal, not yet read by usQuality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation Patient-centered outcomes on quality of life and anthroposophic healthcare: a qualitative triangulation study.
Purpose: To provide a qualitative investigation of aspects that matter to patients regarding quality of life (QOL) and other perceived treatment effects of anthroposophic healthcare (AH). It is a first step in the development of patient reported outcome measures (PROMs) for AH. Hence, it will contribute to the evaluation of AH quality from patients' perspectives.
Method: Within-method triangulation of four qualitative data sources is: (1) Survey of 2063 patients of AH general practitioners; single open item; (2) Survey of 34 patients of AH nurses; single open item; (3) and (4) Sixteen semi-structured interviews with patients. The data sources contained patients' qualitative reports on contribution of treatment to QOL, other perceived treatment effects and/or quality of care aspects. Content analysis Construction of items and domains by open, axial and selective coding.
Results: Twelve domains regarding quality of life are found: Recovery/Symptom reduction, Active contribution/Autonomy, General well-being, Meaning, Rest/Relaxation, Functioning, Energy/Strength, Care relationship, Natural healing, Mindful inner attitude, Being well informed and Social relations. The interviews demonstrate relations between domains.
Conclusions: The findings give a comprehensive insight into aspects of care that are relevant to patients, providing a first step to develop PROMs for AH. Findings show a broadening of domains compared to existing measurement instruments and show close similarities with the recently developed concept of "positive health." Extending QOL instruments with a broader set of domains would give concrete tools to improve evaluation of quality of care and make this evaluation more in line with aspects that matter to AH patients.
Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation · 9 citationsread the source →
Griffin SJ, Simmons RK, Prevost AT, Williams KM, Hardeman W, Sutton S, Brage S, Ekelund U, Parker RA, Wareham NJ, Kinmonth AL, ADDITION-Plus study team. (2014)MEDLINE-indexed journal, not yet read by usDiabetologia · randomised controlled trial Multiple behaviour change intervention and outcomes in recently diagnosed type 2 diabetes: the ADDITION-Plus randomised controlled trial.
Aims/hypothesis: The aim of this study was to assess whether or not a theory-based behaviour change intervention delivered by trained and quality-assured lifestyle facilitators can achieve and maintain improvements in physical activity, dietary change, medication adherence and smoking cessation in people with recently diagnosed type 2 diabetes.
Methods: An explanatory randomised controlled trial was conducted in 34 general practices in Eastern England (Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care-Plus [ADDITION-Plus]). In all, 478 patients meeting eligibility criteria (age 40 to 69 years with recently diagnosed screen or clinically detected diabetes) were individually randomised to receive either intensive treatment (n = 239) or intensive treatment plus a theory-based behaviour change intervention led by a facilitator external to the general practice team (n = 239). Randomisation was central and independent using a partial minimisation procedure to balance stratifiers between treatment arms. Facilitators taught patients skills to facilitate change in and maintenance of key health behaviours, including goal setting, self-monitoring and building habits. Primary outcomes included physical activity energy expenditure (individually calibrated heart rate monitoring and movement sensing), change in objectively measured fruit and vegetable intake (plasma vitamin C), medication adherence (plasma drug levels) and smoking status (plasma cotinine levels) at 1 year. Measurements, data entry and laboratory analysis were conducted with staff unaware of participants' study group allocation.
Results: Of 475 participants still alive, 444 (93%; intervention group 95%, comparison group 92%) attended 1-year follow-up. There were no significant differences between groups in physical activity (difference: +1.50 kJ kg(-1) day(-1); 95% CI -1.74, 4.74), plasma vitamin C (difference: -3.84 μmol/l; 95% CI -8.07, 0.38), smoking (OR 1.37; 95% CI 0.77, 2.43) and plasma drug levels (difference in metformin levels: -119.5 μmol/l; 95% CI -335.0, 95.9). Cardiovascular risk factors and self-reported behaviour improved in both groups with no significant differences between groups.
Conclusions/interpretation: For patients with recently diagnosed type 2 diabetes receiving intensive treatment in UK primary care, a facilitator-led individually tailored behaviour change intervention did not improve objectively measured health behaviours or cardiovascular risk factors over 1 year.
Trial registration: ISRCTN99175498 FUNDING: The trial is supported by the Medical Research Council, the Wellcome Trust, National Health Service R&D support funding (including the Primary Care Research and Diabetes Research Networks) and National Institute of Health Research under its Programme Grants for Applied Research scheme. The Primary Care Unit is supported by NIHR Research funds. Bio-Rad provided equipment for HbA1c testing during the screening phase.
Diabetologia · randomised controlled trial · 28 citationsread the source →
Volunteer group participation and subsequent health and well-being among older adults in Japan: An outcome-wide longitudinal approach.
Background: Prior studies have underscored the importance of studying volunteering in the East Asian context. However, no study has conducted a holistic assessment of the relationship between volunteering and the multidimensional health and well-being outcomes of East Asian populations using a strong study design for causal inference. To address this gap, this study examined the associations between volunteer group participation and the subsequent health and well-being of Japanese older adults.
Methods: Three waves of data (2013, 2016, and 2019), obtained from the Japan Gerontological Evaluation Study-a nationwide cohort study of physically and cognitively independent older adults, aged ≥ 65 years, in Japan-were utilized. Exposure was evaluated as the frequency of volunteer group participation: ≥ 1/week, 1 - 3 times a month, a few times a year, and none (2016). As outcomes, 40 indicators of health and well-being were assessed across seven domains (2019): physical/cognitive health, health behaviors, mental health, subjective well-being, social well-being, pro-social/altruistic behaviors, and cognitive social capital. We included 47,318 respondents for four outcomes (death, dementia, and functional disability [any level and level 2 or greater]) and 34,187 respondents for the 36 other outcomes.
Results: More frequent volunteering (≥ 1/week) was associated with higher social well-being outcomes, more frequent pro-social/altruistic behaviors and outings, and fewer depressive symptoms, even after considering multiple testing.
Conclusion: Throughout the three-year follow-ups, volunteer group participation was beneficial for depressive symptoms, social well-being, and other proximal outcomes.
Archives of gerontology and geriatrics · 2 citationsread the source →
Islamophobia, Health, and Public Health: A Systematic Literature Review.
Background: In 2017, a "Muslim ban" on immigrants to the United States was coupled with a continued rise in Islamophobia and hate crimes toward Muslims. Islamophobia undermines health equity, yet delineating the effects of Islamophobia globally is challenging as it affects a myriad of groups (geographically, racially, and socially). Additionally, stereotypes equate all Muslims with populations from the Middle East and South Asia. To date, health research pays insufficient attention to Islamophobia, Muslims, and those racialized to be Muslim.
Objectives: This literature review advances our understanding of racism and health by examining the racialization of religion, by specifically examining Islamophobia as a form of discrimination.
Search methods: Per PRISMA guidelines, we conducted a search in October 2017 using PubMed-MEDLINE and a combination of terms. We identified additional articles using other search engines. For inclusion, articles needed to include a descriptor of discrimination, contain an identifier of Muslim or Muslim-like identity (i.e., groups commonly perceived as Muslim, including Arabs, Middle Easterners, North Africans, and South Asians), include a health outcome, be in English, and be published between 1990 and 2017.
Selection criteria: We identified 111 unique peer-reviewed articles. We excluded articles that did not meet the following criteria: (1) examined Islamophobia, discrimination, or racism among a Muslim or Muslim-like population; (2) included a health outcome or discussion of health disparities; and (3) was conducted in North America, Europe, Australia, or New Zealand. This yielded 53 articles.
Results: The majority of studies (n = 34; 64%) were quantitative. The remaining studies were qualitative (n = 7; 13%), mixed methods (n = 2; 4%), or reviews (n = 10; 19%). Most studies were based in the United States (n = 31; 58%). Nearly half of the reviewed studies examined mental health (n = 24; 45%), and one fourth examined physical health or health behaviors (n = 13; 25%). Others focused on both physical and mental health (n = 10; 19%) or health care seeking (n = 7; 13%). Studies showed associations between Islamophobia and poor mental health, suboptimal health behaviors, and unfavorable health care-seeking behaviors.
Conclusions: This study elucidates the associations between Islamophobia, health, and socioecological determinants of health. Future studies should examine the intersectional nature of Islamophobia and include validated measures, representative samples, subgroup analyses, and comparison groups. More methodologically rigorous studies of Islamophobia and health are needed. Public Health Implications. Addressing the discrimination-related poor health that Muslims and racialized Muslim-like subgroups experience is central to the goals of health equity and assurance of the fundamental right to health.
American journal of public health · systematic review · 73 citationsread the source →
Interoception in anxiety, depression, and psychosis: a review.
Research has examined the relationship between interoception and anxiety, depression, and psychosis; however, it is unclear which aspects of interoception have been systematically examined, what the combined findings are, and which areas require further research. To answer these questions, we systematically searched and narratively synthesised relevant reviews, meta-analyses, and theory papers (total n = 34). Existing systematic reviews and meta-analyses (anxiety n = 2; depression n = 2; psychosis n = 0), focus on cardiac interoceptive accuracy (heartbeat perception), and indicate that heartbeat perception is not systematically impaired in anxiety or depression. Heartbeat perception might be poorer in people with psychosis, but further evidence is needed. Other aspects of interoception, such as different body systems and processing levels, have been studied but not systematically reviewed. We highlight studies examining these alternative bodily domains and levels, review the efficacy of interoception-based psychological interventions, and make suggestions for future research.
Funding: Wellcome Trust UK.
EClinicalMedicine · review · 25 citationsread the source →
Afifi TO, Bolton SL, Mota N, Marrie RA, Stein MB, Enns MW, El-Gabalawy R, Bernstein CN, Mackenzie C, VanTil L, MacLean MB, Wang JL, Patten S, Asmundson GJG, Sareen J. (2021)MEDLINE-indexed journal, not yet read by usCanadian journal of psychiatry. Revue canadienne de psychiatrie Rationale and Methodology of the 2018 Canadian Armed Forces Members and Veterans Mental Health Follow-up Survey (CAFVMHS): A 16-year Follow-up Survey: Raison D'être Et Méthodologie De L'enquête De Suivi Sur La Santé Mentale Des Membres Des Forces Armées Canadiennes Et Des Anciens Combattants, 2018 (ESSMFACM).
Objective: Knowledge is limited regarding the longitudinal course and predictors of mental health problems, suicide, and physical health outcomes among military and veterans. Statistics Canada, in collaboration with researchers at the University of Manitoba and an international team, conducted the Canadian Armed Forces Members and Veterans Mental Health Follow-Up Survey (CAFVMHS). Herein, we describe the rationale and methods of this important survey.
Method: The CAFVMHS is a longitudinal survey design with 2 time points (2002 and 2018). Regular Force military personnel who participated in the first Canadian Community Health Survey Cycle 1.2-Mental Health and Well-Being, Canadian Forces Supplement (CCHS-CFS) in 2002 (N = 5,155) were reinterviewed in 2018 (n = 2,941). The World Mental Health Survey-Composite International Diagnostic Interview was used with the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria.
Results: The CAFVMHS includes 2,941 respondents (66% veterans; 34% active duty) and includes data on mental disorder diagnoses, physical health conditions, substance use, medication use, general health, mental health services, perceived need for care, social support, moral injury, deployment experiences, stress, physical activity, military-related sexual assault, childhood experiences, and military and sociodemographic information.
Conclusions: The CAFVMHS provides a unique opportunity to further understand the health and well-being of military personnel in Canada over time to inform intervention and prevention strategies and improve outcomes. The data are available through the Statistics Canada Research Data Centres across Canada and can be used cross-sectionally or be longitudinally linked to the 2002 CCHS-CFS data.
Canadian journal of psychiatry. Revue canadienne de psychiatrie · 18 citationsread the source →
Interventions for the treatment of metastatic extradural spinal cord compression in adults.
Background: Metastatic extradural spinal cord compression (MESCC) is treated with radiotherapy, corticosteroids, and surgery, but there is uncertainty regarding their comparative effects. This is an updated version of the original Cochrane review published in theCochrane Database of Systematic Reviews (Issue 4, 2008).
Objectives: To determine the efficacy and safety of radiotherapy, surgery and corticosteroids in MESCC.
Search methods: In March 2015, we updated previous searches (July 2008 and December 2013) of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, LILACS, CANCERLIT, clinical trials registries, conference proceedings, and references, without language restrictions. We also contacted experts for relevant published, unpublished and ongoing trials.
Selection criteria: Randomised controlled trials (RCTs) of radiotherapy, surgery and corticosteroids in adults with MESCC.
Data collection and analysis: Three authors independently screened and selected trials, assessed risk of bias, and extracted data. We sought clarifications from trial authors. Where possible, we pooled relative risks with their 95% confidence intervals, using a random effects model if heterogeneity was significant. We assessed overall evidence-quality using the GRADE approach.
Main results: This update includes seven trials involving 876 (723 evaluable) adult participants (19 to 87 years) in high-income countries. Most were free of the risk of bias. Different radiotherapy doses and schedulesTwo equivalence trials in people with MESCC and a poor prognosis evaluated different radiotherapy doses and schedules. In one, a single dose (8 Gray (Gy)) of radiotherapy (RT) was as effective as short-course RT (16 Gy in two fractions over one week) in enhancing ambulation in the short term (65% versus 69%; risk ratio (RR) was 0.93, (95% confidence interval (CI) 0.82 to 1.04); 303 participants; moderate quality evidence). The regimens were also equally effective in reducing analgesic and narcotic use (34% versus 40%; RR 0.85, 95% CI 0.62 to 1.16; 271 participants), and in maintaining urinary continence (90% versus 87%; RR 1.03, 95% CI 0.96 to 1.1; 303 participants) in the short term (moderate quality evidence). In the other trial, split-course RT (30 Gy in eight fractions over two weeks) was no different from short-course RT in enhancing ambulation (70% versus 68%; RR 1.02, 95% CI 0.9 to 1.15; 276 participants); reducing analgesic and narcotic use (49% versus 38%; RR 1.27, 95% CI 0.96 to 1.67; 262 participants); and in maintaining urinary continence (87% versus 90%; RR 0.97, 0.93 to 1.02; 275 participants) in the short term (moderate quality evidence). Median survival was similar with the three RT regimens (four months). Local tumour recurrence may be more common with single-dose compared to short-course RT (6% versus 3%; RR 2.21, 95% CI 0.69 to 7.01; 303 participants) and with short-course compared to split-course RT (4% versus 0%; RR 0.1, 95% CI 0.01 to 1.72; 276 participants), but these differences were not statistically significant (low quality evidence). Gastrointestinal adverse effects were infrequent with the three RT regimens (moderate quality evidence), and serious adverse events or post-radiotherapy myelopathy were not noted. We did not find trials comparing radiotherapy schedules in people with MESCC and a good prognosis. Surgery plus radiotherapy compared to radiotherapyLaminectomy plus RT offered no advantage over RT in one small trial with 29 participants (very low quality evidence). In another trial that was stopped early for apparent benefit, decompressive surgery plus RT resulted in better ambulatory rates (84% versus 57%; RR 1.48, 95% CI 1.16 to 1.90; 101 participants, low quality evidence). Narcotic use may also be lower, and bladder control may also be maintained longer than with than RT in selected patients (low quality evidence). Median survival was longer after surgery (126 days versus 100 days), but the proportions surviving at one month (94% versus 86%; RR 1.09, 95% CI 0.96 to 1.24; 101 participants) did not differ significantly (low quality evidence). Serious adverse events were not noted. Significant benefits with surgery occurred only in people younger than 65 years. High dose corticosteroids compared to moderate dose or no corticosteroidsData from three small trials suggest that high-dose steroids may not differ from moderate-dose or no corticosteroids in enhancing ambulation (60% versus 55%; RR 1.08, 95% CI 0.81 to 1.45; 3 RCTs, 105 participants); survival over two years (11% versus 10%; RR 1.11, 95% CI 0.24 to 5.05; 1 RCT, 57 participants); pain reduction (78% versus 91%; RR 0.86, 95% CI 0.62 to 1.20; 1 RCT, 25 participants); or urinary continence (63% versus 53%; RR 1.18, 95% CI 0.66 to 2.13; 1 RCT, 34 participants; low quality evidence). Serious adverse effects were more frequent with high-dose corticosteroids (17% versus 0%; RR 8.02, 95% CI 1.03 to 62.37; 2 RCTs, 77 participants; moderate quality evidence).None of the trials reported satisfaction with care or quality of life in participants.
Authors' conclusions: Based on current evidence, ambulant adults with MESCC with stable spines and predicted survival of less than six months will probably benefit as much from one dose of radiation (8 Gy) as from two doses (16 Gy) or eight doses (30 Gy). We are unsure if a single dose is as effective as two or more doses in preventing local tumour recurrence. Laminectomy preceding radiotherapy may offer no benefits over radiotherapy alone. Decompressive surgery followed by radiotherapy may benefit ambulant and non-ambulant adults younger than 65 years of age, with poor prognostic factors for radiotherapy, a single area of compression, paraplegia for less than 48 hours, and a predicted survival of more than six months. We are uncertain whether high doses of corticosteroids offer any benefits over moderate doses or indeed no corticosteroids; but high-dose steroids probably significantly increases the risk of serious adverse effects. Early detection; and treatment based on neurological status, age and estimated survival, are crucial with all treatment modalities. Most of the evidence was of low quality. High-quality evidence from more trials is needed to clarify current uncertainties, and some studies are in progress.
The Cochrane database of systematic reviews · meta-analysis · 39 citationsread the source →
Depression and telomere length: A meta-analysis.
Background: Several recent studies have investigated the relationship between telomere length and depression with inconsistent results. This meta-analysis examined whether telomere length and depression are associated and explored factors that might affect this association.
Methods: Studies measuring telomere length in subjects with clinically significant unipolar depression were included. A comprehensive search strategy identified studies in PubMed, MEDLINE, PsycINFO, Global Health, The Cochrane Library, and Web of Science. A structured data abstraction form was used and studies were appraised for inclusion or exclusion using a priori conditions. Analyses were conducted using standardized mean differences in a continuous random effects model.
Results: Thirty-eight studies (N=34,347) met the inclusion criteria. The association between depression and telomere length was significant, with a Cohen's d effect size of -0.205 (p<0.0001, I(2)=42%). Depression severity significantly associated with telomere length (p=0.03). Trim and fill analysis indicated the presence of publication bias (p=0.003), but that the association remained highly significant after accounting for the bias. Subgroup analysis revealed depression assessment tools, telomere measurement techniques, source tissue and comorbid medical conditions significantly affected the relationship.
Limitations: Other potentially important sub-groups, including antidepressant use, have not been investigated in sufficient detail or number yet and thus were not addressed in this meta-analysis.
Conclusions: There is a negative association between depression and telomere length. Further studies are needed to clarify potential causality underlying this association and to elucidate the biology linking depression and this cellular marker of stress exposure and aging.
Journal of affective disorders · meta-analysis · 211 citationsread the source →
Murphy R, Hutton P. (2018)MEDLINE-indexed journal, not yet read by usJournal of child psychology and psychiatry, and allied disciplines · meta-analysis Practitioner Review: Therapist variability, patient-reported therapeutic alliance, and clinical outcomes in adolescents undergoing mental health treatment - a systematic review and meta-analysis.
Background: Previous meta-analyses have only found small correlations (r = .10 to r = .19) between therapeutic alliance and clinical outcomes in samples of adolescents receiving psychological therapy. Although study-level variables have been found to moderate this, little is known about the impact of therapist variability. The present meta-analysis aimed to address this gap by using patient-therapist ratio as a moderator variable.
Methods: Contrary to previous reviews of adolescent alliance, individual effect sizes were extracted using a preregistered conceptual hierarchy. Controlling for treatment-level confounds, a random effects meta-analysis assessed the moderating effect of patient-therapist ratio on the alliance-outcome relationship in predefined single-predictor and multipredictor meta-regressions.
Results: The alliance-outcome relationship was found to be larger than previously thought (k = 28, N = 2,911, r = .29, 95% Confidence Interval 0.21, 0.37; p < .0001, I2 = 80%). When study samples exceeding the adolescent 12-19 age range were removed, the correlation rose (k = 15, N = 1,797, r = .34, 95% Confidence Interval 0.23, 0.45; p < .0001, I2 = 83%). In contrast to research with adults, patient-therapist ratio did not moderate this relationship in either single-predictor (p = .26) or multi-predictor (p = .22) models.
Conclusions: The alliance-outcome relationship for adolescents was larger than previously thought, and comparable to estimates in adult samples. The failure of patient-therapist ratio to moderate its strength, however, challenges the hypothesis that variability in therapist characteristics is an important determinant of the alliance-outcome effect in this age group.
Journal of child psychology and psychiatry, and allied disciplines · meta-analysis · 48 citationsread the source →
Life course health consequences and associated annual costs of adverse childhood experiences across Europe and North America: a systematic review and meta-analysis.
Background: An increasing number of studies are identifying associations between adverse childhood experiences (ACEs) and ill health throughout the life course. We aimed to calculate the proportions of major risk factors for and causes of ill health that are attributable to one or multiple types of ACE and the associated financial costs.
Methods: In this systematic review and meta-analysis, we searched for studies in which risk data in individuals with ACEs were compared with these data in those without ACEs. We searched six electronic databases (MEDLINE, CINAHL, PsycINFO, Applied Social Sciences Index and Abstracts, Criminal Justice Databases, and the Education Resources Information Center) for quantitative studies published between Jan 1, 1990, and July 11, 2018, that reported risks of health-related behaviours and causes of ill health in adults that were associated with cumulative measures of ACEs (ie, number of ACEs). We included studies in adults in populations that did not have a high risk of ACEs, that had sample sizes of at least 1000 people, and that provided ACE prevalence data. We calculated the pooled RR for risk factors (harmful alcohol use, illicit drug use, smoking, and obesity) and causes of ill health (cancer, diabetes, cardiovascular disease, respiratory disease, anxiety, and depression) associated with ACEs. RRs were used to estimate the population-attributable fractions (PAFs) of risk attributable to ACEs and the disability-adjusted life-years (DALYs) and financial costs associated with ACEs. This study was prospectively registered in PROSPERO (CRD42018090356).
Findings: Of 4387 unique articles found following our initial search, after review of the titles (and abstracts, when the title was relevant), we assessed 880 (20%) full-text articles. We considered 221 (25%) full-text articles for inclusion, of which 23 (10%) articles met all selection criteria for our meta-analysis. We found a pooled prevalence of 23·5% of individuals (95% CI 18·7-28·5) with one ACE and 18·7% (14·7-23·2) with two or more ACEs in Europe (from ten studies) and of 23·4% of individuals (22·0-24·8) with one ACE and 35·0% (31·6-38·4) with two or more ACEs in north America (from nine studies). Illicit drug use had the highest PAFs associated with ACEs of all the risk factors assessed in both regions (34·1% in Europe; 41·1% in north America). In both regions, PAFs of causes of ill health were highest for mental illness outcomes: ACEs were attributed to about 30% of cases of anxiety and 40% of cases of depression in north America and more than a quarter of both conditions in Europe. Costs of cardiovascular disease attributable to ACEs were substantially higher than for most other causes of ill health because of higher DALYs for this condition. Total annual costs attributable to ACEs were estimated to be US$581 billion in Europe and $748 billion in north America. More than 75% of these costs arose in individuals with two or more ACEs.
Interpretation: Millions of adults across Europe and north America live with a legacy of ACEs. Our findings suggest that a 10% reduction in ACE prevalence could equate to annual savings of 3 million DALYs or $105 billion. Programmes to prevent ACEs and moderate their effects are available. Rebalancing expenditure towards ensuring safe and nurturing childhoods would be economically beneficial and relieve pressures on health-care systems.
Funding: World Health Organization Regional Office for Europe.
The Lancet. Public health · meta-analysis · 660 citationsread the source →
Pharmacological interventions for promoting smoking cessation during pregnancy.
Background: Tobacco smoking in pregnancy causes serious health problems for the developing fetus and mother. When used by non-pregnant smokers, pharmacotherapies (nicotine replacement therapy (NRT), bupropion, and varenicline) are effective for increasing smoking cessation, however their efficacy and safety in pregnancy remains unknown. Electronic cigarettes (ECs) are becoming widely used, but their efficacy and safety when used for smoking cessation in pregnancy are also unknown.
Objectives: To determine the efficacy and safety of smoking cessation pharmacotherapies and ECs used during pregnancy for smoking cessation in later pregnancy and after childbirth, and to determine adherence to smoking cessation pharmacotherapies and ECs for smoking cessation during pregnancy.
Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (20 May 2019), trial registers, and grey literature, and checked references of retrieved studies.
Selection criteria: Randomised controlled trials (RCTs) conducted in pregnant women, comparing smoking cessation pharmacotherapy or EC use with either placebo or no pharmacotherapy/EC control. We excluded quasi-randomised, cross-over, and within-participant designs, and RCTs with additional intervention components not matched between trial arms.
Data collection and analysis: We followed standard Cochrane methods. The primary efficacy outcome was smoking cessation in later pregnancy; safety was assessed by 11 outcomes (principally birth outcomes) that indicated neonatal and infant well-being. We also collated data on adherence to trial treatments. We calculated the risk ratio (RR) or mean difference (MD) and the 95% confidence intervals (CI) for each outcome for each study, where possible. We grouped eligible studies according to the type of comparison. We carried out meta-analyses where appropriate.
Main results: We included 11 trials that enrolled a total of 2412 pregnant women who smoked at enrolment, nine trials of NRT and two trials of bupropion as adjuncts to behavioural support, with comparable behavioural support provided in the control arms. No trials investigated varenicline or ECs. We assessed four trials as at low risk of bias overall. The overall certainty of the evidence was low across outcomes and comparisons as assessed using GRADE, with reductions in confidence due to risk of bias, imprecision, and inconsistency. Compared to placebo and non-placebo (behavioural support only) controls, there was low-certainty evidence that NRT increased the likelihood of smoking abstinence in later pregnancy (RR 1.37, 95% CI 1.08 to 1.74; I² = 34%, 9 studies, 2336 women). However, in subgroup analysis by comparator type, there was a subgroup difference between placebo-controlled and non-placebo controlled RCTs (test for subgroup differences P = 0.008). There was unclear evidence of an effect in placebo-controlled RCTs (RR 1.21, 95% CI 0.95 to 1.55; I² = 0%, 6 studies, 2063 women), whereas non-placebo-controlled trials showed clearer evidence of a benefit (RR 8.55, 95% CI 2.05 to 35.71; I² = 0%, 3 studies, 273 women). An additional subgroup analysis in which studies were grouped by the type of NRT used found no difference in the effectiveness of NRT in those using patches or fast-acting NRT (test for subgroup differences P = 0.08). There was no evidence of a difference between NRT and control groups in rates of miscarriage, stillbirth, premature birth, birthweight, low birthweight, admissions to neonatal intensive care, caesarean section, congenital abnormalities, or neonatal death. In one study infants born to women who had been randomised to NRT had higher rates of 'survival without developmental impairment' at two years of age compared to the placebo group. Non-serious adverse effects observed with NRT included headache, nausea, and local reactions (e.g. skin irritation from patches or foul taste from gum), but data could not be pooled. Adherence to NRT treatment regimens was generally low. We identified low-certainty evidence that there was no difference in smoking abstinence rates observed in later pregnancy in women using bupropion when compared to placebo control (RR 0.74, 95% CI 0.21 to 2.64; I² = 0%, 2 studies, 76 women). Evidence investigating the safety outcomes of bupropion use was sparse, but the existing evidence showed no difference between the bupropion and control group.
Authors' conclusions: NRT used for smoking cessation in pregnancy may increase smoking cessation rates in late pregnancy. However, this evidence is of low certainty, as the effect was not evident when potentially biased, non-placebo-controlled RCTs were excluded from the analysis. Future studies may therefore change this conclusion. We found no evidence that NRT has either positive or negative impacts on birth outcomes; however, the evidence for some of these outcomes was also judged to be of low certainty due to imprecision and inconsistency. We found no evidence that bupropion may be an effective aid for smoking cessation during pregnancy, and there was little evidence evaluating its safety in this population. Further research evidence on the efficacy and safety of pharmacotherapy and EC use for smoking cessation in pregnancy is needed, ideally from placebo-controlled RCTs that achieve higher adherence rates and that monitor infants' outcomes into childhood. Future RCTs of NRT should investigate higher doses than those tested in the studies included in this review.
The Cochrane database of systematic reviews · meta-analysis · 92 citationsread the source →
Exercise training undertaken by people within 12 months of lung resection for non-small cell lung cancer.
Background: Decreased exercise capacity and health-related quality of life (HRQoL) are common in people following lung resection for non-small cell lung cancer (NSCLC). Exercise training has been demonstrated to confer gains in exercise capacity and HRQoL for people with a range of chronic conditions, including chronic obstructive pulmonary disease and heart failure, as well as in people with prostate and breast cancer. A programme of exercise training may also confer gains in these outcomes for people following lung resection for NSCLC. This systematic review updates our 2013 systematic review.
Objectives: The primary aim of this review was to determine the effects of exercise training on exercise capacity and adverse events in people following lung resection (with or without chemotherapy) for NSCLC. The secondary aims were to determine the effects of exercise training on other outcomes such as HRQoL, force-generating capacity of peripheral muscles, pressure-generating capacity of the respiratory muscles, dyspnoea and fatigue, feelings of anxiety and depression, lung function, and mortality.
Search methods: We searched for additional randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2019, Issue 2 of 12), MEDLINE (via PubMed) (2013 to February 2019), Embase (via Ovid) (2013 to February 2019), SciELO (The Scientific Electronic Library Online) (2013 to February 2019), and PEDro (Physiotherapy Evidence Database) (2013 to February 2019).
Selection criteria: We included RCTs in which participants with NSCLC who underwent lung resection were allocated to receive either exercise training, which included aerobic exercise, resistance exercise, or a combination of both, or no exercise training.
Data collection and analysis: Two review authors screened the studies and identified those eligible for inclusion. We used either postintervention values (with their respective standard deviation (SD)) or mean changes (with their respective SD) in the meta-analyses that reported results as mean difference (MD). In meta-analyses that reported results as standardised mean difference (SMD), we placed studies that reported postintervention values and those that reported mean changes in separate subgroups. We assessed the certainty of evidence for each outcome by downgrading or upgrading the evidence according to GRADE criteria.
Main results: Along with the three RCTs included in the original version of this review (2013), we identified an additional five RCTs in this update, resulting in a total of eight RCTs involving 450 participants (180 (40%) females). The risk of selection bias in the included studies was low and the risk of performance bias high. Six studies explored the effects of combined aerobic and resistance training; one explored the effects of combined aerobic and inspiratory muscle training; and one explored the effects of combined aerobic, resistance, inspiratory muscle training and balance training. On completion of the intervention period, compared to the control group, exercise capacity expressed as the peak rate of oxygen uptake (VO2peak) and six-minute walk distance (6MWD) was greater in the intervention group (VO2peak: MD 2.97 mL/kg/min, 95% confidence interval (CI) 1.93 to 4.02 mL/kg/min, 4 studies, 135 participants, moderate-certainty evidence; 6MWD: MD 57 m, 95% CI 34 to 80 m, 5 studies, 182 participants, high-certainty evidence). One adverse event (hip fracture) related to the intervention was reported in one of the included studies. The intervention group also achieved greater improvements in the physical component of general HRQoL (MD 5.0 points, 95% CI 2.3 to 7.7 points, 4 studies, 208 participants, low-certainty evidence); improved force-generating capacity of the quadriceps muscle (SMD 0.75, 95% CI 0.4 to 1.1, 4 studies, 133 participants, moderate-certainty evidence); and less dyspnoea (SMD -0.43, 95% CI -0.81 to -0.05, 3 studies, 110 participants, very low-certainty evidence). We observed uncertain effects on the mental component of general HRQoL, disease-specific HRQoL, handgrip force, fatigue, and lung function. There were insufficient data to comment on the effect of exercise training on maximal inspiratory and expiratory pressures and feelings of anxiety and depression. Mortality was not reported in the included studies.
Authors' conclusions: Exercise training increased exercise capacity and quadriceps muscle force of people following lung resection for NSCLC. Our findings also suggest improvements on the physical component score of general HRQoL and decreased dyspnoea. This systematic review emphasises the importance of exercise training as part of the postoperative management of people with NSCLC.
The Cochrane database of systematic reviews · meta-analysis · 76 citationsread the source →
Benefits and Harms of Sodium-Glucose Co-Transporter 2 Inhibitors in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis.
Objective: Sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are a novel drug class for the treatment of diabetes. We aimed at describing the maximal benefits and risks associated with SGLT2-i for patients with type 2 diabetes.
Design: Systematic review and meta-analysis.
Data sources and study selection: We included double-blinded, randomised controlled trials (RCTs) evaluating SGLT2-i administered in the highest approved therapeutic doses (canagliflozin 300 mg/day, dapagliflozin 10 mg/day, and empagliflozin 25 mg/day) for ≥12 weeks. Comparison groups could receive placebo or oral antidiabetic drugs (OAD) including metformin, sulphonylureas (SU), or dipeptidyl peptidase 4 inhibitors (DPP-4-i). Trials were identified through electronic databases and extensive manual searches. Primary outcomes were glycated haemoglobin A1c (HbA1c) levels, serious adverse events, death, severe hypoglycaemia, ketoacidosis and CVD. Secondary outcomes were fasting plasma glucose, body weight, blood pressure, heart rate, lipids, liver function tests, creatinine and adverse events including infections. The quality of the evidence was assessed using GRADE.
Results: Meta-analysis of 34 RCTs with 9,154 patients showed that SGLT2-i reduced HbA1c compared with placebo (mean difference -0.69%, 95% confidence interval -0.75 to -0.62%). We downgraded the evidence to 'low quality' due to variability and evidence of publication bias (P = 0.015). Canagliflozin was associated with the largest reduction in HbA1c (-0.85%, -0.99% to -0.71%). There were no differences between SGLT2-i and placebo for serious adverse events. SGLT2-i increased the risk of urinary and genital tract infections and increased serum creatinine, and exerted beneficial effects on bodyweight, blood pressure, lipids and alanine aminotransferase (moderate to low quality evidence). Analysis of 12 RCTs found a beneficial effect of SGLT2-i on HbA1c compared with OAD (-0.20%, -0.28 to -0.13%; moderate quality evidence).
Conclusion: This review includes a large number of patients with type 2 diabetes and found that SGLT2-i reduces HbA1c with a notable increased risk in non-serious adverse events. The analyses may overestimate the intervention benefit due bias.
PloS one · meta-analysis · 174 citationsread the source →
Health system and community level interventions for improving antenatal care coverage and health outcomes.
Background: The World Health Organization (WHO) recommends at least four antenatal care (ANC) visits for all pregnant women. Almost half of pregnant women worldwide, and especially in developing countries do not receive this amount of care. Poor attendance of ANC is associated with delivery of low birthweight babies and more neonatal deaths. ANC may include education on nutrition, potential problems with pregnancy or childbirth, child care and prevention or detection of disease during pregnancy. This review focused on community-based interventions and health systems-related interventions.
Objectives: To assess the effects of health system and community interventions for improving coverage of antenatal care and other perinatal health outcomes.
Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (7 June 2015) and reference lists of retrieved studies.
Selection criteria: We included randomised controlled trials (RCTs), quasi-randomised trials and cluster-randomised trials. Trials of any interventions to improve ANC coverage were eligible for inclusion. Trials were also eligible if they targeted specific and related outcomes, such as maternal or perinatal death, but also reported ANC coverage.
Data collection and analysis: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy.
Main results: We included 34 trials involving approximately 400,000 women. Some trials tested community-based interventions to improve uptake of antenatal care (media campaigns, education or financial incentives for pregnant women), while other trials looked at health systems interventions (home visits for pregnant women or equipment for clinics). Most trials took place in low- and middle-income countries, and 29 of the 34 trials used a cluster-randomised design. We assessed 30 of the 34 trials as of low or unclear overall risk of bias. Comparison 1: One intervention versus no interventionWe found marginal improvements in ANC coverage of at least four visits (average odds ratio (OR) 1.11, 95% confidence interval (CI) 1.01 to 1.22; participants = 45,022; studies = 10; Heterogeneity: Tau² = 0.01; I² = 52%; high quality evidence). Sensitivity analysis with a more conservative intra-cluster correlation co-efficient (ICC) gave similar marginal results. Excluding one study at high risk of bias shifted the marginal pooled estimate towards no effect. There was no effect on pregnancy-related deaths (average OR 0.69, 95% CI 0.45 to 1.08; participants = 114,930; studies = 10; Heterogeneity: Tau² = 0.00; I² = 0%; low quality evidence), perinatal mortality (average OR 0.98, 95% CI 0.90 to 1.07; studies = 15; Heterogeneity: Tau² = 0.01; I² = 58%; moderate quality evidence) or low birthweight (average OR 0.94, 95% CI 0.82 to 1.06; studies = five; Heterogeneity: Tau² = 0.00; I² = 5%; high quality evidence). Single interventions led to marginal improvements in the number of women who delivered in health facilities (average OR 1.08, 95% CI 1.02 to 1.15; studies = 10; Heterogeneity: Tau² = 0.00; I² = 0%; high quality evidence), and in the proportion of women who had at least one ANC visit (average OR 1.68, 95% CI 1.02 to 2.79; studies = six; Heterogeneity: Tau² = 0.24; I² = 76%; moderate quality evidence). Results for ANC coverage (at least four and at least one visit) and for perinatal mortality had substantial statistical heterogeneity. Single interventions did not improve the proportion of women receiving tetanus protection (average OR 1.03, 95% CI 0.92 to 1.15; studies = 8; Heterogeneity: Tau² = 0.01; I² = 57%). No study reported onintermittent prophylactic treatment for malaria. Comparison 2: Two or more interventions versus no interventionWe found no improvements in ANC coverage of four or more visits (average OR 1.48, 95% CI 0.99 to 2.21; participants = 7840; studies = six; Heterogeneity: Tau² = 0.10; I² = 48%; low quality evidence) or pregnancy-related deaths (average OR 0.70, 95% CI 0.39 to 1.26; participants = 13,756; studies = three; Heterogeneity: Tau² = 0.00; I² = 0%; moderate quality evidence). However, combined interventions led to improvements in ANC coverage of at least one visit (average OR 1.79, 95% CI 1.47 to 2.17; studies = five; Heterogeneity: Tau² = 0.00; I² = 0%; moderate quality evidence), perinatal mortality (average OR 0.74, 95% CI 0.57 to 0.95; studies = five; Heterogeneity: Tau² = 0.06; I² = 83%; moderate quality evidence) and low birthweight (average OR 0.61, 95% CI 0.46 to 0.80; studies = two; Heterogeneity: Tau² = 0.00; I² = 0%; moderate quality evidence). Meta-analyses for both ANC coverage four or more visits and perinatal mortality had substantial statistical heterogeneity. Combined interventions improved the proportion of women who had tetanus protection (average OR 1.48, 95% CI 1.18 to 1.87; studies = 3; Heterogeneity: Tau² = 0.01; I² = 33%). No trial in this comparison reported on intermittent prophylactic treatment for malaria. Comparison 3: Two interventions compared head to head. No trials found. Comparison 4: One intervention versus a combination of interventionsThere was no difference in ANC coverage (four or more visits and at least one visit), pregnancy-related deaths, deliveries in a health facility or perinatal mortality. No trials in this comparison reported on low birthweight orintermittent prophylactic treatment of malaria.
Authors' conclusions: Implications for practice - Single interventions may improve ANC coverage (at least one visit and four or more visits) and deliveries in health facilities. Combined interventions may improve ANC coverage (at least one visit), reduce perinatal mortality and reduce the occurrence of low birthweight. The effects of the interventions are unrelated to whether they are community or health system interventions. Implications for research - More details should be provided in reporting numbers of events, group totals and the ICCs used to adjust for cluster effects. Outcomes should be reported uniformly so that they are comparable to commonly-used population indicators. We recommend further cluster-RCTs of pregnant women and women in their reproductive years, using combinations of interventions and looking at outcomes that are important to pregnant women, such as maternal and perinatal morbidity and mortality, alongside the explanatory outcomes along the pathway of care: ANC coverage, the services provided during ANC and deliveries in health facilities.
The Cochrane database of systematic reviews · meta-analysis · 117 citationsread the source →
Effectiveness of brief alcohol interventions in primary care populations.
Background: Excessive drinking is a significant cause of mortality, morbidity and social problems in many countries. Brief interventions aim to reduce alcohol consumption and related harm in hazardous and harmful drinkers who are not actively seeking help for alcohol problems. Interventions usually take the form of a conversation with a primary care provider and may include feedback on the person's alcohol use, information about potential harms and benefits of reducing intake, and advice on how to reduce consumption. Discussion informs the development of a personal plan to help reduce consumption. Brief interventions can also include behaviour change or motivationally-focused counselling. This is an update of a Cochrane Review published in 2007.
Objectives: To assess the effectiveness of screening and brief alcohol intervention to reduce excessive alcohol consumption in hazardous or harmful drinkers in general practice or emergency care settings.
Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and 12 other bibliographic databases to September 2017. We searched Alcohol and Alcohol Problems Science Database (to December 2003, after which the database was discontinued), trials registries, and websites. We carried out handsearching and checked reference lists of included studies and relevant reviews.
Selection criteria: We included randomised controlled trials (RCTs) of brief interventions to reduce hazardous or harmful alcohol consumption in people attending general practice, emergency care or other primary care settings for reasons other than alcohol treatment. The comparison group was no or minimal intervention, where a measure of alcohol consumption was reported. 'Brief intervention' was defined as a conversation comprising five or fewer sessions of brief advice or brief lifestyle counselling and a total duration of less than 60 minutes. Any more was considered an extended intervention. Digital interventions were not included in this review.
Data collection and analysis: We used standard methodological procedures expected by Cochrane. We carried out subgroup analyses where possible to investigate the impact of factors such as gender, age, setting (general practice versus emergency care), treatment exposure and baseline consumption.
Main results: We included 69 studies that randomised a total of 33,642 participants. Of these, 42 studies were added for this update (24,057 participants). Most interventions were delivered in general practice (38 studies, 55%) or emergency care (27 studies, 39%) settings. Most studies (61 studies, 88%) compared brief intervention to minimal or no intervention. Extended interventions were compared with brief (4 studies, 6%), minimal or no intervention (7 studies, 10%). Few studies targeted particular age groups: adolescents or young adults (6 studies, 9%) and older adults (4 studies, 6%). Mean baseline alcohol consumption was 244 g/week (30.5 standard UK units) among the studies that reported these data. Main sources of bias were attrition and lack of provider or participant blinding. The primary meta-analysis included 34 studies (15,197 participants) and provided moderate-quality evidence that participants who received brief intervention consumed less alcohol than minimal or no intervention participants after one year (mean difference (MD) -20 g/week, 95% confidence interval (CI) -28 to -12). There was substantial heterogeneity among studies (I² = 73%). A subgroup analysis by gender demonstrated that both men and women reduced alcohol consumption after receiving a brief intervention. We found moderate-quality evidence that brief alcohol interventions have little impact on frequency of binges per week (MD -0.08, 95% CI -0.14 to -0.02; 15 studies, 6946 participants); drinking days per week (MD -0.13, 95% CI -0.23 to -0.04; 11 studies, 5469 participants); or drinking intensity (-0.2 g/drinking day, 95% CI -3.1 to 2.7; 10 studies, 3128 participants).We found moderate-quality evidence of little difference in quantity of alcohol consumed when extended and no or minimal interventions were compared (-14 g/week, 95% CI -37 to 9; 6 studies, 1296 participants). There was little difference in binges per week (-0.08, 95% CI -0.28 to 0.12; 2 studies, 456 participants; moderate-quality evidence) or difference in days drinking per week (-0.45, 95% CI -0.81 to -0.09; 2 studies, 319 participants; moderate-quality evidence). Extended versus no or minimal intervention provided little impact on drinking intensity (9 g/drinking day, 95% CI -26 to 9; 1 study, 158 participants; low-quality evidence).Extended intervention had no greater impact than brief intervention on alcohol consumption, although findings were imprecise (MD 2 g/week, 95% CI -42 to 45; 3 studies, 552 participants; low-quality evidence). Numbers of binges were not reported for this comparison, but one trial suggested a possible drop in days drinking per week (-0.5, 95% CI -1.2 to 0.2; 147 participants; low-quality evidence). Results from this trial also suggested very little impact on drinking intensity (-1.7 g/drinking day, 95% CI -18.9 to 15.5; 147 participants; very low-quality evidence).Only five studies reported adverse effects (very low-quality evidence). No participants experienced any adverse effects in two studies; one study reported that the intervention increased binge drinking for women and two studies reported adverse events related to driving outcomes but concluded they were equivalent in both study arms. Sources of funding were reported by 67 studies (87%). With two exceptions, studies were funded by government institutes, research bodies or charitable foundations. One study was partly funded by a pharmaceutical company and a brewers association, another by a company developing diagnostic testing equipment.
Authors' conclusions: We found moderate-quality evidence that brief interventions can reduce alcohol consumption in hazardous and harmful drinkers compared to minimal or no intervention. Longer counselling duration probably has little additional effect. Future studies should focus on identifying the components of interventions which are most closely associated with effectiveness.
The Cochrane database of systematic reviews · meta-analysis · 409 citationsread the source →
Mobile health (m-health) smartphone interventions for adolescents and adults with overweight or obesity.
Background: Obesity is considered to be a risk factor for various diseases, and its incidence has tripled worldwide since 1975. In addition to potentially being at risk for adverse health outcomes, people with overweight or obesity are often stigmatised. Behaviour change interventions are increasingly delivered as mobile health (m-health) interventions, using smartphone apps and wearables. They are believed to support healthy behaviours at the individual level in a low-threshold manner.
Objectives: To assess the effects of integrated smartphone applications for adolescents and adults with overweight or obesity.
Search methods: We searched CENTRAL, MEDLINE, PsycINFO, CINAHL, and LILACS, as well as the trials registers ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform on 2 October 2023 (date of last search for all databases). We placed no restrictions on the language of publication.
Selection criteria: Participants were adolescents and adults with overweight or obesity. Eligible interventions were integrated smartphone apps using at least two behaviour change techniques. The intervention could target physical activity, cardiorespiratory fitness, weight loss, healthy diet, or self-efficacy. Comparators included no or minimal intervention (NMI), a different smartphone app, personal coaching, or usual care. Eligible studies were randomised controlled trials of any duration with a follow-up of at least three months.
Data collection and analysis: We used standard Cochrane methodology and the RoB 2 tool. Important outcomes were physical activity, body mass index (BMI) and weight, health-related quality of life, self-efficacy, well-being, change in dietary behaviour, and adverse events. We focused on presenting studies with medium- (6 to < 12 months) and long-term (≥ 12 months) outcomes in our summary of findings table, following recommendations in the core outcome set for behavioural weight management interventions.
Main results: We included 18 studies with 2703 participants. Interventions lasted from 2 to 24 months. The mean BMI in adults ranged from 27 to 50, and the median BMI z-score in adolescents ranged from 2.2 to 2.5. Smartphone app versus no or minimal intervention Thirteen studies compared a smartphone app versus NMI in adults; no studies were available for adolescents. The comparator comprised minimal health advice, handouts, food diaries, smartphone apps unrelated to weight loss, and waiting list. Measures of physical activity: at 12 months' follow-up, a smartphone app compared to NMI probably reduces moderate to vigorous physical activity (MVPA) slightly (mean difference (MD) -28.9 min/week (95% confidence interval (CI) -85.9 to 28; 1 study, 650 participants; moderate-certainty evidence)). We are very uncertain about the results of estimated energy expenditure and cardiorespiratory fitness at eight months' follow-up. A smartphone app compared with NMI probably results in little to no difference in changes in total activity time at 12 months' follow-up and leisure time physical activity at 24 months' follow-up. Anthropometric measures: a smartphone app compared with NMI may reduce BMI (MD of BMI change -2.6 kg/m2, 95% CI -6 to 0.8; 2 studies, 146 participants; very low-certainty evidence) at six to eight months' follow-up, but the evidence is very uncertain. At 12 months' follow-up, a smartphone app probably resulted in little to no difference in BMI change (MD -0.1 kg/m2, 95% CI -0.4 to 0.3; 1 study; 650 participants; moderate-certainty evidence). A smartphone app compared with NMI may result in little to no difference in body weight change (MD -2.5 kg, 95% CI -6.8 to 1.7; 3 studies, 1044 participants; low-certainty evidence) at 12 months' follow-up. At 24 months' follow-up, a smartphone app probably resulted in little to no difference in body weight change (MD 0.7 kg, 95% CI -1.2 to 2.6; 1 study, 245 participants; moderate-certainty evidence). A smartphone app compared with NMI may result in little to no difference in self-efficacy for a physical activity score at eight months' follow-up, but the results are very uncertain. A smartphone app probably results in little to no difference in quality of life and well-being at 12 months (moderate-certainty evidence) and in little to no difference in various measures used to inform dietary behaviour at 12 and 24 months' follow-up. We are very uncertain about adverse events, which were only reported narratively in two studies (very low-certainty evidence). Smartphone app versus another smartphone app Two studies compared different versions of the same app in adults, showing no or minimal differences in outcomes. One study in adults compared two different apps (calorie counting versus ketogenic diet) and suggested a slight reduction in body weight at six months in favour of the ketogenic diet app. No studies were available for adolescents. Smartphone app versus personal coaching Only one study compared a smartphone app with personal coaching in adults, presenting data at three months. Two studies compared these interventions in adolescents. A smartphone app resulted in little to no difference in BMI z-score compared to personal coaching at six months' follow-up (MD 0, 95% CI -0.2 to 0.2; 1 study; 107 participants). Smartphone app versus usual care Only one study compared an app with usual care in adults but only reported data at three months on participant satisfaction. No studies were available for adolescents. We identified 34 ongoing studies.
Authors' conclusions: The available evidence is limited and does not demonstrate a clear benefit of smartphone applications as interventions for adolescents or adults with overweight or obesity. While the number of studies is growing, the evidence remains incomplete due to the high variability of the apps' features, content and components, which complicates direct comparisons and assessment of their effectiveness. Comparisons with either no or minimal intervention or personal coaching show minor effects, which are mostly not clinically significant. Minimal data for adolescents also warrants further research. Evidence is also scarce for low- and middle-income countries as well as for people with different socio-economic and cultural backgrounds. The 34 ongoing studies suggest sustained interest in the topic, with new evidence expected to emerge within the next two years. In practice, clinicians and healthcare practitioners should carefully consider the potential benefits, limitations, and evolving research when recommending smartphone apps to adolescents and adults with overweight or obesity.
The Cochrane database of systematic reviews · meta-analysis · 28 citationsread the source →
Omega-3 fatty acid addition during pregnancy.
Background: Higher intakes of foods containing omega-3 long-chain polyunsaturated fatty acids (LCPUFA), such as fish, during pregnancy have been associated with longer gestations and improved perinatal outcomes. This is an update of a review that was first published in 2006.
Objectives: To assess the effects of omega-3 LCPUFA, as supplements or as dietary additions, during pregnancy on maternal, perinatal, and neonatal outcomes and longer-term outcomes for mother and child.
Search methods: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (16 August 2018), and reference lists of retrieved studies.
Selection criteria: Randomised controlled trials (RCTs) comparing omega-3 fatty acids (as supplements or as foods, stand-alone interventions, or with a co-intervention) during pregnancy with placebo or no omega-3, and studies or study arms directly comparing omega-3 LCPUFA doses or types. Trials published in abstract form were eligible for inclusion.
Data collection and analysis: Two review authors independently assessed study eligibility, extracted data, assessed risk of bias in trials and assessed quality of evidence for prespecified birth/infant, maternal, child/adult and health service outcomes using the GRADE approach.
Main results: In this update, we included 70 RCTs (involving 19,927 women at low, mixed or high risk of poor pregnancy outcomes) which compared omega-3 LCPUFA interventions (supplements and food) compared with placebo or no omega-3. Overall study-level risk of bias was mixed, with selection and performance bias mostly at low risk, but there was high risk of attrition bias in some trials. Most trials were conducted in upper-middle or high-income countries; and nearly half the trials included women at increased/high risk for factors which might increase the risk of adverse maternal and birth outcomes. Preterm birth < 37 weeks (13.4% versus 11.9%; risk ratio (RR) 0.89, 95% confidence interval (CI) 0.81 to 0.97; 26 RCTs, 10,304 participants; high-quality evidence) and early preterm birth < 34 weeks (4.6% versus 2.7%; RR 0.58, 95% CI 0.44 to 0.77; 9 RCTs, 5204 participants; high-quality evidence) were both lower in women who received omega-3 LCPUFA compared with no omega-3. Prolonged gestation > 42 weeks was probably increased from 1.6% to 2.6% in women who received omega-3 LCPUFA compared with no omega-3 (RR 1.61 95% CI 1.11 to 2.33; 5141 participants; 6 RCTs; moderate-quality evidence).For infants, there was a possibly reduced risk of perinatal death (RR 0.75, 95% CI 0.54 to 1.03; 10 RCTs, 7416 participants; moderate-quality evidence: 62/3715 versus 83/3701 infants) and possibly fewer neonatal care admissions (RR 0.92, 95% CI 0.83 to 1.03; 9 RCTs, 6920 participants; moderate-quality evidence - 483/3475 infants versus 519/3445 infants). There was a reduced risk of low birthweight (LBW) babies (15.6% versus 14%; RR 0.90, 95% CI 0.82 to 0.99; 15 trials, 8449 participants; high-quality evidence); but a possible small increase in large-for-gestational age (LGA) babies (RR 1.15, 95% CI 0.97 to 1.36; 6 RCTs, 3722 participants; moderate-quality evidence, for omega-3 LCPUFA compared with no omega-3. Little or no difference in small-for-gestational age or intrauterine growth restriction (RR 1.01, 95% CI 0.90 to 1.13; 8 RCTs, 6907 participants; moderate-quality evidence) was seen. For the maternal outcomes, there is insufficient evidence to determine the effects of omega-3 on induction post-term (average RR 0.82, 95% CI 0.22 to 2.98; 3 trials, 2900 participants; low-quality evidence), maternal serious adverse events (RR 1.04, 95% CI 0.40 to 2.72; 2 trials, 2690 participants; low-quality evidence), maternal admission to intensive care (RR 0.56, 95% CI 0.12 to 2.63; 2 trials, 2458 participants; low-quality evidence), or postnatal depression (average RR 0.99, 95% CI 0.56 to 1.77; 2 trials, 2431 participants; low-quality evidence). Mean gestational length was greater in women who received omega-3 LCPUFA (mean difference (MD) 1.67 days, 95% CI 0.95 to 2.39; 41 trials, 12,517 participants; moderate-quality evidence), and pre-eclampsia may possibly be reduced with omega-3 LCPUFA (RR 0.84, 95% CI 0.69 to 1.01; 20 trials, 8306 participants; low-quality evidence).For the child/adult outcomes, very few differences between antenatal omega-3 LCPUFA supplementation and no omega-3 were observed in cognition, IQ, vision, other neurodevelopment and growth outcomes, language and behaviour (mostly low-quality to very low-quality evidence). The effect of omega-3 LCPUFA on body mass index at 19 years (MD 0, 95% CI -0.83 to 0.83; 1 trial, 243 participants; very low-quality evidence) was uncertain. No data were reported for development of diabetes in the children of study participants.
Authors' conclusions: In the overall analysis, preterm birth < 37 weeks and early preterm birth < 34 weeks were reduced in women receiving omega-3 LCPUFA compared with no omega-3. There was a possibly reduced risk of perinatal death and of neonatal care admission, a reduced risk of LBW babies; and possibly a small increased risk of LGA babies with omega-3 LCPUFA.For our GRADE quality assessments, we assessed most of the important perinatal outcomes as high-quality (e.g. preterm birth) or moderate-quality evidence (e.g. perinatal death). For the other outcome domains (maternal, child/adult and health service outcomes) GRADE ratings ranged from moderate to very low, with over half rated as low. Reasons for downgrading across the domain were mostly due to design limitations and imprecision. Omega-3 LCPUFA supplementation during pregnancy is an effective strategy for reducing the incidence of preterm birth, although it probably increases the incidence of post-term pregnancies. More studies comparing omega-3 LCPUFA and placebo (to establish causality in relation to preterm birth) are not needed at this stage. A further 23 ongoing trials are still to report on over 5000 women, so no more RCTs are needed that compare omega-3 LCPUFA against placebo or no intervention. However, further follow-up of completed trials is needed to assess longer-term outcomes for mother and child, to improve understanding of metabolic, growth and neurodevelopment pathways in particular, and to establish if, and how, outcomes vary by different types of omega-3 LCPUFA, timing and doses; or by characteristics of women.
The Cochrane database of systematic reviews · meta-analysis · 254 citationsread the source →
Effect of essential amino acid supplementation on quality of life, amino acid profile and strength in institutionalized elderly patients.
Background & aims: This study assessed the efficacy of supplemented essential amino acids on depressive symptoms, nutrition, muscle function, daily physical activity, and health-related quality of life (HRQoL) of institutionalized elderly patients.
Methods: Forty-one patients (58.5% women; mean age 79.8 yrs) with sequelae of coronary artery disease (73%), femoral fracture (34%), were randomly assigned to receive oral essential amino acids 4 gr 2 times a day for 8 weeks or isocaloric placebo. Before randomization and 8 weeks after the protocol started, the following variables were measured: depressive symptoms (Geriatric Depression Scale, GDS), nutritional panel (Mini Nutritional Assessment, MNA; serum albumin and prealbumin levels), muscle strength (Hand Grip, HG), Activity Daily Life (ADL), Quality of Life (SF-36, HRQoL) and amino acid profile.
Results: Compared with the placebo group, EAA patients improved nutrition (MNA score 22.6 ± 1.5 post vs 21.8 ± 1.6 pre; p < 0. 04, albumin g/dl 4.04 ± 0.35 post vs 3.88 ± 0.3 pre; p < 0.01), GDS(score 10.3 ± 1.75 post vs 13.85 ± 3.37 pre; p < 0.001), HG (Kg 19.75 ± 1.7 post vs 18.68 ± 1.36 pre; p = 0.001), ADL (p < 0.04) and both physical and mental components of SF-36 (p < 0.002).
Conclusions: Oral supplementation with essential amino acids improved several determinants of quality of life in institutionalized elderly patients, including depressive symptoms, nutrition, muscle function and daily life activity.
Clinical nutrition (Edinburgh, Scotland) · randomised controlled trial · 62 citationsread the source →
Quantifying and visualising heterogeneity in cumulative adverse childhood experiences scores: A national survey of US children.
Objective: Adverse childhood experiences (ACEs) scores mask substantial heterogeneity within the 2-, 3-, and ≥ 4-ACE exposure categories. This exposure heterogeneity has not been systematically investigated.
Methods: Using the US-based 2023 National Survey of Children's Health (N = 55,162), caregivers reported lifetime exposure to 10 ACEs covering family dysfunction and community- and discrimination-related adversities. We quantified heterogeneity of ACE co-occurrence within ACE exposure categories using combinatorial coverage (CC; proportion of possible patterns observed) and visualised common patterns with an UpSet.
Results: Analyses used complete ACE data (N = 51,468; 93.3% of the total sample); co-occurrence analyses were restricted to children with ≥2 ACEs (n = 7897). Across the 2-, 3-, and ≥ 4-ACE categories, 582 of 1013 combinations were observed: all 45/45 patterns for 2 ACEs (CC₂ = 1.00), 110/120 for 3 ACEs (CC₃ = 0.92), and 427/848 for ≥4 ACEs (CC ≥ 4 = 0.50). Fifty combinations met the display threshold (unweighted n ≥ 30) and accounted for 5204 (66%) of children with ≥2 ACEs. Parental divorce/separation appeared in 34 of the 50 displayed patterns, household substance use in 23, and household mental illness in 20.
Conclusions: ACE scores masked heterogeneity in exposure patterns. Simple diagnostics such as combinatorial coverage and UpSet plots can make this heterogeneity explicit and may support pattern-specific analyses of outcomes.
Preventive medicineread the source →
Knowledge, attitudes, and planned practice of HIV-positive to HIV-positive transplantation in US transplant centers.
Background: HIV+ donor organs can now be transplanted into HIV+ recipients (HIV D+/R+) following the HIV Organ Policy Equity (HOPE) Act. Implementation of the HOPE Act requires transplant center awareness and support of HIV D+/R+ transplants.
Methods: To assess center-level barriers to implementation, we surveyed 209 transplant centers on knowledge, attitudes, and planned HIV D+/R+ protocols.
Results: Responding centers (n = 114; 56%) represented all UNOS regions. Fifty centers (93 organ programs) planned HIV D+/R+ protocols (kidney n = 48, liver n = 34, pancreas n = 8, heart n = 2, lung = 1), primarily in the eastern United States (28/50). Most (91.2%) were aware that HIV D+/R+ transplantation is legal; 21.4% were unaware of research restrictions. Respondents generally agreed with HOPE research criteria except the required experience with ≥5 HIV+ transplants by organ type. Centers planning HIV D+/R+ protocols had higher transplant volume, HIV+ recipient volume, increased infectious risk donor utilization, and local HIV prevalence (P < 0.01). Centers not planning HIV D+/R+ protocols were more likely to believe their HIV+ candidates would not accept HIV+ donor organs (P < 0.001). Most centers (83.2%) supported HIV+ living donation.
Conclusions: Although many programs plan HIV D+/R+ transplantation, center-level barriers remain including geographic clustering of kidney/liver programs and concerns about HIV+ candidate willingness to accept HIV+ donor organs.
Clinical transplantation · 26 citationsread the source →
Behavioural and cognitive-behavioural interventions for outwardly directed aggressive behaviour in people with intellectual disabilities.
Background: Outwardly directed aggressive behaviour in people with intellectual disabilities is a significant issue that may lead to poor quality of life, social exclusion and inpatient psychiatric admissions. Cognitive and behavioural approaches have been developed to manage aggressive behaviour but the effectiveness of these interventions on reducing aggressive behaviour and other outcomes are unclear. This is the third update of this review and adds nine new studies, resulting in a total of 15 studies in this review.
Objectives: To evaluate the efficacy of behavioural and cognitive-behavioural interventions on outwardly directed aggressive behaviour compared to usual care, wait-list controls or no treatment in people with intellectual disability. We also evaluated enhanced interventions compared to non-enhanced interventions.
Search methods: We used standard, extensive Cochrane search methods. The latest search date was March 2022. We revised the search terms to include positive behaviour support (PBS).
Selection criteria: We included randomised and quasi-randomised trials of children and adults with intellectual disability of any duration, setting and any eligible comparator.
Data collection and analysis: We used standard Cochrane methods. Our primary outcomes were change in 1. aggressive behaviour, 2. ability to control anger, and 3. adaptive functioning, and 4.
Adverse effects: Our secondary outcomes were change in 5. mental state, 6. medication, 7. care needs and 8. quality of life, and 9. frequency of service utilisation and 10. user satisfaction data. We used GRADE to assess certainty of evidence for each outcome. We expressed treatment effects as mean differences (MD) or odds ratios (OR), with 95% confidence intervals (CI). Where possible, we pooled data using a fixed-effect model.
Main results: This updated version comprises nine new studies giving 15 included studies and 921 participants. The update also adds new interventions including parent training (two studies), mindfulness-based positive behaviour support (MBPBS) (two studies), reciprocal imitation training (RIT; one study) and dialectical behavioural therapy (DBT; one study). It also adds two new studies on PBS. Most studies were based in the community (14 studies), and one was in an inpatient forensic service. Eleven studies involved adults only. The remaining studies involved children (one study), children and adolescents (one study), adolescents (one study), and adolescents and adults (one study). One study included boys with fragile X syndrome. Six studies were conducted in the UK, seven in the USA, one in Canada and one in Germany. Only five studies described sources of funding. Four studies compared anger management based on cognitive behaviour therapy to a wait-list or no treatment control group (n = 263); two studies compared PBS with treatment as usual (TAU) (n = 308); two studies compared carer training on mindfulness and PBS with PBS only (n = 128); two studies involving parent training on behavioural approaches compared to wait-list control or TAU (n = 99); one study of mindfulness to a wait-list control (n = 34); one study of adapted dialectal behavioural therapy compared to wait-list control (n = 21); one study of RIT compared to an active control (n = 20) and one study of modified relaxation compared to an active control group (n = 12). There was moderate-certainty evidence that anger management may improve severity of aggressive behaviour post-treatment (MD -3.50, 95% CI -6.21 to -0.79; P = 0.01; 1 study, 158 participants); very low-certainty evidence that it might improve self-reported ability to control anger (MD -8.38, 95% CI -14.05 to -2.71; P = 0.004, I2 = 2%; 3 studies, 212 participants), adaptive functioning (MD -21.73, 95% CI -36.44 to -7.02; P = 0.004; 1 study, 28 participants) and psychiatric symptoms (MD -0.48, 95% CI -0.79 to -0.17; P = 0.002; 1 study, 28 participants) post-treatment; and very low-certainty evidence that it does not improve quality of life post-treatment (MD -5.60, 95% CI -18.11 to 6.91; P = 0.38; 1 study, 129 participants) or reduce service utilisation and costs at 10 months (MD 102.99 British pounds, 95% CI -117.16 to 323.14; P = 0.36; 1 study, 133 participants). There was moderate-certainty evidence that PBS may reduce aggressive behaviour post-treatment (MD -7.78, 95% CI -15.23 to -0.32; P = 0.04, I2 = 0%; 2 studies, 275 participants) and low-certainty evidence that it probably does not reduce aggressive behaviour at 12 months (MD -5.20, 95% CI -13.27 to 2.87; P = 0.21; 1 study, 225 participants). There was low-certainty evidence that PBS does not improve mental state post-treatment (OR 1.44, 95% CI 0.83 to 2.49; P = 1.21; 1 study, 214 participants) and very low-certainty evidence that it might not reduce service utilisation at 12 months (MD -448.00 British pounds, 95% CI -1660.83 to 764.83; P = 0.47; 1 study, 225 participants). There was very low-certainty evidence that mindfulness may reduce incidents of physical aggression (MD -2.80, 95% CI -4.37 to -1.23; P < 0.001; 1 study; 34 participants) and low-certainty evidence that MBPBS may reduce incidents of aggression post-treatment (MD -10.27, 95% CI -14.86 to -5.67; P < 0.001, I2 = 87%; 2 studies, 128 participants). Reasons for downgrading the certainty of evidence were risk of bias (particularly selection and performance bias); imprecision (results from single, often small studies, wide CIs, and CIs crossing the null effect); and inconsistency (statistical heterogeneity).
Authors' conclusions: There is moderate-certainty evidence that cognitive-behavioural approaches such as anger management and PBS may reduce outwardly directed aggressive behaviour in the short term but there is less certainty about the evidence in the medium and long term, particularly in relation to other outcomes such as quality of life. There is some evidence to suggest that combining more than one intervention may have cumulative benefits. Most studies were small and there is a need for larger, robust randomised controlled trials, particularly for interventions where the certainty of evidence is very low. More trials are needed that focus on children and whether psychological interventions lead to reductions in the use of psychotropic medications.
The Cochrane database of systematic reviews · systematic review · 6 citationsread the source →
Impact of breastfeeding interventions among United States minority women on breastfeeding outcomes: a systematic review.
Background: In the U.S., strong ethnic/racial, socioeconomic, demographic, and geographic breastfeeding (BF) inequities persist, and African American and Hispanic women are less likely to meet their breastfeeding goals compared to White women. This systematic review (SR) was designed to answer the question: What is the impact of breastfeeding interventions targeting ethnic/racial minority women in the U.S. on improving BF initiation, duration and exclusivity rates?
Methods: The SR was conducted following the Institute of Medicine Guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. The study protocol was developed and registered a priori in PROSPERO (ID#CRD42020177764). The electronical databases searched was MEDLINE All (Ovid). Search strategies were led by the team's expert public health librarian using both controlled vocabulary and free text queries and were tested against a validated set of relevant papers included in existing reviews. The GRADE methodology was used to assess the quality of the studies.
Results: We included 60 studies that had randomized (n = 25), observational (n = 24), quasi-experimental (n = 9), or cross-sectional (n = 2) designs. The studies focused on populations that were multi-ethnic/racial (n = 22), only Hispanic (n = 24), only Black (n = 13), and only American Indian (n = 1). The study interventions were classified following the socioecological model: macrosystem/policy level (n = 6); community level (n=51), which included healthcare organizations (n = 34), The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) (n = 9), and community organizations/public health institutions (n = 8); and interpersonal level (n = 3).
Conclusions: Policy and community level interventions delivered through WIC, healthcare facilities, and community agencies) are likely to improve BF outcomes among women of color. The combination of interventions at different levels of the socioecological model has not been studied among minority women in the U.S. Implementation science research is needed to learn how best to scale up and sustain effective BF interventions, taking into account the needs and wants of minority women. Thus, it is strongly recommended to conduct large scale implementation research studies addressesing how to strengthen the different health and social environments surrounding women of color in the U.S. to improving their BF outcomes.
International journal for equity in health · systematic review · 97 citationsread the source →
Effects of physical activity programs on sleep outcomes in older adults: a systematic review.
Background: One in two older adults report sleep problems, which not only cause fatigue, but also negatively affect general functioning, activities of daily living, and physical and mental health. Although it is known that physical activity is positively associated with sleep in older adults, the effects of physical activity programs on sleep in older adults has not been reviewed. The aim of this systematic review was to systematically review the effects of physical activity programs on sleep in generally healthy older adults aged 60+ years.
Methods: Searches were performed in PubMed, Embase, Web of Science, SPORTDiscus, PEDro and CINAHL. The methodological quality of the included studies was rated using the 'Quality Assessment Tool for Quantitative Studies'. Only studies of moderate and strong quality were included. This review was registered in PROSPERO (CRD42018094007).
Results: Fourteen studies met the inclusion criteria (six randomised controlled trials and eight pretest-posttest studies). Of these studies, five were moderate and nine were strong quality studies. Mean age of study samples ranged from 64 to 76 years. Exercise programs included various activities aimed at improving mobility, endurance and strength. Intervention duration ranged from 2 weeks to 12 months. Eleven studies used subjective measures of sleep, two used objective measures and one used both. Sixteen different sleep outcomes were reported. All but one study, found at least one significant improvement on sleep outcomes. No significantly detrimental effects were reported. Effect sizes, calculated in ten studies, ranged from 0,34-1,55 and were substantial (≥0,8) in four studies.
Conclusions: This systematic review suggests that exercise programs positively affect various aspects of sleep in generally healthy older adults. More specifically, moderate intensity exercise programs, with a frequency of three times per week and a duration of 12 weeks up to 6 months, showed the highest number of significant improvements in different sleep outcomes in older adults. Furthermore, programs that offered single exercise types, such as Baduanjin, Tai chi and the silver yoga program, or a combination of exercises showed the highest proportion of significant versus reported effects on sleep outcomes.
The international journal of behavioral nutrition and physical activity · systematic review · 148 citationsread the source →
Welch V, Dewidar O, Tanjong Ghogomu E, Abdisalam S, Al Ameer A, Barbeau VI, Brand K, Kebedom K, Benkhalti M, Kristjansson E, Madani MT, Antequera Martín AM, Mathew CM, McGowan J, McLeod W, Park HA, Petkovic J, Riddle A, Tugwell P, Petticrew M, Trawin J, Wells GA. (2022)MEDLINE-indexed journal, not yet read by usThe Cochrane database of systematic reviews · systematic review How effects on health equity are assessed in systematic reviews of interventions.
Background: Enhancing health equity is endorsed in the Sustainable Development Goals. The failure of systematic reviews to consider potential differences in effects across equity factors is cited by decision-makers as a limitation to their ability to inform policy and program decisions. OBJECTIVES: To explore what methods systematic reviewers use to consider health equity in systematic reviews of effectiveness.
Search methods: We searched the following databases up to 26 February 2021: MEDLINE, PsycINFO, the Cochrane Methodology Register, CINAHL, Education Resources Information Center, Education Abstracts, Criminal Justice Abstracts, Hein Index to Foreign Legal Periodicals, PAIS International, Social Services Abstracts, Sociological Abstracts, Digital Dissertations and the Health Technology Assessment Database. We searched SCOPUS to identify articles that cited any of the included studies on 10 June 10 2021. We contacted authors and searched the reference lists of included studies to identify additional potentially relevant studies.
Selection criteria: We included empirical studies of cohorts of systematic reviews that assessed methods for measuring effects on health inequalities. We define health inequalities as unfair and avoidable differences across socially stratifying factors that limit opportunities for health. We operationalised this by assessing studies which evaluated differences in health across any component of the PROGRESS-Plus acronym, which stands for Place of residence, Race/ethnicity/culture/language, Occupation, Gender or sex, Religion, Education, Socioeconomic status, Social capital. "Plus" stands for other factors associated with discrimination, exclusion, marginalisation or vulnerability such as personal characteristics (e.g. age, disability), relationships that limit opportunities for health (e.g. children in a household with parents who smoke) or environmental situations which provide limited control of opportunities for health (e.g. school food environment).
Data collection and analysis: Two review authors independently extracted data using a pre-tested form. Risk of bias was appraised for included studies according to the potential for bias in selection and detection of systematic reviews. MAIN RESULTS: In total, 48,814 studies were identified and the titles and abstracts were screened in duplicate. In this updated review, we identified an additional 124 methodological studies published in the 10 years since the first version of this review, which included 34 studies. Thus, 158 methodological studies met our criteria for inclusion. The methods used by these studies focused on evidence relevant to populations experiencing health inequity (108 out of 158 studies), assess subgroup analysis across PROGRESS-Plus (26 out of 158 studies), assess analysis of a gradient in effect across PROGRESS-Plus (2 out of 158 studies) or use a combination of subgroup analysis and focused approaches (20 out of 158 studies). The most common PROGRESS-Plus factors assessed were age (43 studies), socioeconomic status in 35 studies, low- and middle-income countries in 24 studies, gender or sex in 22 studies, race or ethnicity in 17 studies, and four studies assessed multiple factors across which health inequity may exist. Only 16 studies provided a definition of health inequity. Five methodological approaches to consider health equity in systematic reviews of effectiveness were identified: 1) descriptive assessment of reporting and analysis in systematic reviews (140 of 158 studies used a type of descriptive method); 2) descriptive assessment of reporting and analysis in original trials (50 studies); 3) analytic approaches which assessed differential effects across one or more PROGRESS-Plus factors (16 studies); 4) applicability assessment (25 studies) and 5) stakeholder engagement (28 studies), which is a new finding in this update and examines the appraisal of whether relevant stakeholders with lived experience of health inequity were included in the design of systematic reviews or design and delivery of interventions. Reporting for both approaches (analytic and applicability) lacked transparency and was insufficiently detailed to enable the assessment of credibility.
Authors' conclusions: There is a need for improvement in conceptual clarity about the definition of health equity, describing sufficient detail about analytic approaches (including subgroup analyses) and transparent reporting of judgments required for applicability assessments in order to consider health equity in systematic reviews of effectiveness.
The Cochrane database of systematic reviews · systematic review · 38 citationsread the source →
Hartmann-Boyce J, Lindson N, Butler AR, McRobbie H, Bullen C, Begh R, Theodoulou A, Notley C, Rigotti NA, Turner T, Fanshawe TR, Hajek P. (2022)MEDLINE-indexed journal, not yet read by usThe Cochrane database of systematic reviews · systematic review Electronic cigarettes for smoking cessation.
Background: Electronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol by heating an e-liquid. Some people who smoke use ECs to stop or reduce smoking, although some organizations, advocacy groups and policymakers have discouraged this, citing lack of evidence of efficacy and safety. People who smoke, healthcare providers and regulators want to know if ECs can help people quit smoking, and if they are safe to use for this purpose. This is a review update conducted as part of a living systematic review.
Objectives: To examine the effectiveness, tolerability, and safety of using electronic cigarettes (ECs) to help people who smoke tobacco achieve long-term smoking abstinence.
Search methods: We searched the Cochrane Tobacco Addiction Group's Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO to 1 July 2022, and reference-checked and contacted study authors. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and randomized cross-over trials, in which people who smoke were randomized to an EC or control condition. We also included uncontrolled intervention studies in which all participants received an EC intervention. Studies had to report abstinence from cigarettes at six months or longer or data on safety markers at one week or longer, or both.
Data collection and analysis: We followed standard Cochrane methods for screening and data extraction. Our primary outcome measures were abstinence from smoking after at least six months follow-up, adverse events (AEs), and serious adverse events (SAEs). Secondary outcomes included the proportion of people still using study product (EC or pharmacotherapy) at six or more months after randomization or starting EC use, changes in carbon monoxide (CO), blood pressure (BP), heart rate, arterial oxygen saturation, lung function, and levels of carcinogens or toxicants, or both. We used a fixed-effect Mantel-Haenszel model to calculate risk ratios (RRs) with a 95% confidence interval (CI) for dichotomous outcomes. For continuous outcomes, we calculated mean differences. Where appropriate, we pooled data in meta-analyses.
Main results: We included 78 completed studies, representing 22,052 participants, of which 40 were RCTs. Seventeen of the 78 included studies were new to this review update. Of the included studies, we rated ten (all but one contributing to our main comparisons) at low risk of bias overall, 50 at high risk overall (including all non-randomized studies), and the remainder at unclear risk. There was high certainty that quit rates were higher in people randomized to nicotine EC than in those randomized to nicotine replacement therapy (NRT) (RR 1.63, 95% CI 1.30 to 2.04; I2 = 10%; 6 studies, 2378 participants). In absolute terms, this might translate to an additional four quitters per 100 (95% CI 2 to 6). There was moderate-certainty evidence (limited by imprecision) that the rate of occurrence of AEs was similar between groups (RR 1.02, 95% CI 0.88 to 1.19; I2 = 0%; 4 studies, 1702 participants). SAEs were rare, but there was insufficient evidence to determine whether rates differed between groups due to very serious imprecision (RR 1.12, 95% CI 0.82 to 1.52; I2 = 34%; 5 studies, 2411 participants). There was moderate-certainty evidence, limited by imprecision, that quit rates were higher in people randomized to nicotine EC than to non-nicotine EC (RR 1.94, 95% CI 1.21 to 3.13; I2 = 0%; 5 studies, 1447 participants). In absolute terms, this might lead to an additional seven quitters per 100 (95% CI 2 to 16). There was moderate-certainty evidence of no difference in the rate of AEs between these groups (RR 1.01, 95% CI 0.91 to 1.11; I2 = 0%; 5 studies, 1840 participants). There was insufficient evidence to determine whether rates of SAEs differed between groups, due to very serious imprecision (RR 1.00, 95% CI 0.56 to 1.79; I2 = 0%; 8 studies, 1272 participants). Compared to behavioural support only/no support, quit rates were higher for participants randomized to nicotine EC (RR 2.66, 95% CI 1.52 to 4.65; I2 = 0%; 7 studies, 3126 participants). In absolute terms, this represents an additional two quitters per 100 (95% CI 1 to 3). However, this finding was of very low certainty, due to issues with imprecision and risk of bias. There was some evidence that (non-serious) AEs were more common in people randomized to nicotine EC (RR 1.22, 95% CI 1.12 to 1.32; I2 = 41%, low certainty; 4 studies, 765 participants) and, again, insufficient evidence to determine whether rates of SAEs differed between groups (RR 1.03, 95% CI 0.54 to 1.97; I2 = 38%; 9 studies, 1993 participants). Data from non-randomized studies were consistent with RCT data. The most commonly reported AEs were throat/mouth irritation, headache, cough, and nausea, which tended to dissipate with continued EC use. Very few studies reported data on other outcomes or comparisons, hence evidence for these is limited, with CIs often encompassing clinically significant harm and benefit.
Authors' conclusions: There is high-certainty evidence that ECs with nicotine increase quit rates compared to NRT and moderate-certainty evidence that they increase quit rates compared to ECs without nicotine. Evidence comparing nicotine EC with usual care/no treatment also suggests benefit, but is less certain. More studies are needed to confirm the effect size. Confidence intervals were for the most part wide for data on AEs, SAEs and other safety markers, with no difference in AEs between nicotine and non-nicotine ECs nor between nicotine ECs and NRT. Overall incidence of SAEs was low across all study arms. We did not detect evidence of serious harm from nicotine EC, but longest follow-up was two years and the number of studies was small. The main limitation of the evidence base remains imprecision due to the small number of RCTs, often with low event rates, but further RCTs are underway. To ensure the review continues to provide up-to-date information to decision-makers, this review is a living systematic review. We run searches monthly, with the review updated when relevant new evidence becomes available. Please refer to the Cochrane Database of Systematic Reviews for the review's current status.
The Cochrane database of systematic reviews · systematic review · 147 citationsread the source →
Exercise as adjunctive therapy for systemic lupus erythematosus.
Background: Systemic lupus erythematosus (SLE) is a rare, chronic autoimmune inflammatory disease with a prevalence varying from 4.3 to 150 people in 100,000, or approximately five million people worldwide. Systemic manifestations frequently include internal organ involvement, a characteristic malar rash on the face, pain in joints and muscles, and profound fatigue. Exercise is purported to be beneficial for people with SLE. For this review, we focused on studies that examined all types of structured exercise as an adjunctive therapy in the management of SLE.
Objectives: To evaluate the benefits and harms of structured exercise as adjunctive therapy for adults with SLE compared with usual pharmacological care, usual pharmacological care plus placebo and usual pharmacological care plus non-pharmacological care.
Search methods: We used standard, extensive Cochrane search methods. The latest search date was 30 March 2022.
Selection criteria: We included randomised controlled trials (RCTs) of exercise as an adjunct to usual pharmacological treatment in SLE compared with placebo, usual pharmacological care alone and another non-pharmacological treatment. Major outcomes were fatigue, functional capacity, disease activity, quality of life, pain, serious adverse events, and withdrawals due to any reason, including any adverse events.
Data collection and analysis: We used standard Cochrane methods. Our major outcomes were 1. fatigue, 2. functional capacity, 3. disease activity, 4. quality of life, 5. pain, 6. serious adverse events, and 7. withdrawals due to any reason. Our minor outcomes were 8. responder rate, 9. aerobic fitness, 10. depression, and 11. anxiety. We used GRADE to assess certainty of evidence. The primary comparison was exercise compared with placebo.
Main results: We included 13 studies (540 participants) in this review. Studies compared exercise as an adjunct to usual pharmacological care (antimalarials, immunosuppressants, and oral glucocorticoids) with usual pharmacological care plus placebo (one study); usual pharmacological care (six studies); and another non-pharmacological treatment such as relaxation therapy (seven studies). Most studies had selection bias, and all studies had performance and detection bias. We downgraded the evidence for all comparisons because of a high risk of bias and imprecision. Exercise plus usual pharmacological care versus placebo plus usual pharmacological care Evidence from a single small study (17 participants) that compared whole body vibration exercise to whole body placebo vibration exercise (vibrations switched off) indicated that exercise may have little to no effect on fatigue, functional capacity, and pain (low-certainty evidence). We are uncertain whether exercise results in fewer or more withdrawals (very low-certainty evidence). The study did not report disease activity, quality of life, and serious adverse events. The study measured fatigue using the self-reported Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue), scale 0 to 52; lower score means less fatigue. People who did not exercise rated their fatigue at 38 points and those who did exercise rated their fatigue at 33 points (mean difference (MD) 5 points lower, 95% confidence interval (CI) 13.29 lower to 3.29 higher). The study measured functional capacity using the self-reported 36-item Short Form health questionnaire (SF-36) Physical Function domain, scale 0 to 100; higher score means better function. People who did not exercise rated their functional capacity at 70 points and those who did exercise rated their functional capacity at 67.5 points (MD 2.5 points lower, 95% CI 23.78 lower to 18.78 higher). The study measured pain using the SF-36 Pain domain, scale 0 to 100; lower scores mean less pain. People who did not exercise rated their pain at 43 points and those who did exercise rated their pain at 34 points (MD 9 points lower, 95% CI 28.88 lower to 10.88 higher). More participants from the exercise group (3/11, 27%) withdrew from the study than the placebo group (1/10, 10%) (risk ratio (RR) 2.73, 95% CI 0.34 to 22.16). Exercise plus usual pharmacological care versus usual pharmacological care alone The addition of exercise to usual pharmacological care may have little to no effect on fatigue, functional capacity, and disease activity (low-certainty evidence). We are uncertain whether the addition of exercise improves pain (very low-certainty evidence), or results in fewer or more withdrawals (very low-certainty evidence). Serious adverse events and quality of life were not reported. Exercise plus usual care versus another non-pharmacological intervention such as receiving information about the disease or relaxation therapy Compared with education or relaxation therapy, exercise may reduce fatigue slightly (low-certainty evidence), may improve functional capacity (low-certainty evidence), probably results in little to no difference in disease activity (moderate-certainty evidence), and may result in little to no difference in pain (low-certainty evidence). We are uncertain whether exercise results in fewer or more withdrawals (very low-certainty evidence). Quality of life and serious adverse events were not reported.
Authors' conclusions: Due to low- to very low-certainty evidence, we are not confident on the benefits of exercise on fatigue, functional capacity, disease activity, and pain, compared with placebo, usual care, or advice and relaxation therapy. Harms data were not well reported.
The Cochrane database of systematic reviews · systematic review · 11 citationsread the source →
Efficacy of metacognitive therapy for prolonged grief disorder: protocol for a randomised controlled trial
INTRODUCTION: Studies of effective psychotherapy for individuals suffering from the effects of prolonged grief disorder (PGD) are scarce. This paper describes the protocol for an evaluation of a metacognitive therapy programme designed specifically for PGD, to reduce the psychological distress and loss of functioning resulting from bereavement. METHODS AND ANALYSIS: The proposed trial comprises three phases. Phase 1 consists of a review of the literature and semistructured interviews with key members of the target population to inform the development of a metacognitive therapy programme for Prolonged Grief. Phase 2 involves a randomised controlled trial to implement and evaluate the programme. Male and female adults (N=34) will be randomly assigned to either a wait list or an intervention group. Measures of PGD, anxiety, depression, rumination, metacognitions and quality of life will be taken pretreatment and posttreatment and at the 3-month and 6-month follow-up. The generalised linear mixed model will be used to assess treatment efficacy. Phase 3 will test the social validity of the programme. DISCUSSION: This study is the first empirical investigation of the efficacy of a targeted metacognitive treatment programme for PGD. A focus on identifying and changing the metacognitive mechanisms underpinning the development and maintenance of prolonged grief is likely to be beneficial to theory and practice. ETHICS: Ethics approval was obtained from Curtin University Human Research Ethics Committee (Approval number HR 41/2013.) TRIAL REGISTRATION NUMBER: ACTRN12613001270707.
BMJ Open · randomised controlled trial · 18 citationsread the source →
Comparative effectiveness of a faith-based HIV intervention for African American women: importance of enhancing religious social capital.
Objectives: We assessed the effectiveness of P4 for Women, a faith-based HIV intervention.
Methods: We used a 2-arm comparative effectiveness trial involving 134 African American women aged 18 to 34 years to compare the effectiveness of the Centers for Disease Control and Prevention-defined evidence-based Sisters Informing Sisters about Topics on AIDS (SISTA) HIV intervention with P4 for Women, an adapted faith-based version of SISTA. Participants were recruited from a large black church in Atlanta, Georgia, and completed assessments at baseline and follow-up.
Results: Both SISTA and P4 for Women had statistically significant effects on this study's primary outcome-consistent condom use in the past 90 days-as well as other sexual behaviors. However, P4 for Women also had statistically significant effects on the number of weeks women were abstinent, on all psychosocial mediators, and most noteworthy, on all measures of religious social capital. Results were achieved by enhancing structural social capital through ministry participation, religious values and norms, linking trust and by reducing negative religious coping. High intervention attendance may indicate the feasibility of conducting faith-based HIV prevention research for African American women.
Conclusions: P4 for Women enhanced abstinence and safer sex practices as well as religious social capital, and was more acceptable than SISTA. Such efforts may assist faith leaders in responding to the HIV epidemic in African American women.
American journal of public health · randomised controlled trial · 55 citationsread the source →
Irungu EM, Mugwanya KK, Mugo NR, Bukusi EA, Donnell D, Odoyo J, Wamoni E, Peacock S, Morton JF, Ngure K, Mugambi M, Mukui I, O'Malley G, Baeten JM, Partners Scale-Up Project Team. (2021)MEDLINE-indexed journal, not yet read by usThe Lancet. Global health · randomised controlled trial Integration of pre-exposure prophylaxis services into public HIV care clinics in Kenya: a pragmatic stepped-wedge randomised trial.
Background: Successful and sustainable models for HIV pre-exposure prophylaxis (PrEP) delivery in public health systems in Africa are needed. We aimed to evaluate the implementation of PrEP delivery integrated in public HIV care clinics in Kenya.
Methods: As part of Kenya's national PrEP roll-out, we conducted a stepped-wedge cluster-randomised pragmatic trial to catalyse scale-up of PrEP delivery integrated in 25 public HIV care clinics. We selected high-volume clinics in these regions (ie, those with a high number of people living with HIV enrolled in HIV care and treatment). Clinics (each representing a cluster) were stratified by region and randomly assigned to the order in which clinic staff would receive PrEP training and ongoing technical support using numbered opaque balls picked from a bag. There was no masking. PrEP provision was done by clinic staff without additional financial support. Data were abstracted from records of individuals initiating PrEP. The primary outcome was the number of people initiating PrEP per clinic per month comparing intervention to control periods. Other outcomes included PrEP continuation, adherence, and incident HIV infections. This trial is registered with ClinicalTrials.gov, NCT03052010.
Findings: After the baseline period, which started in January, 2017, every month two to six HIV care clinics crossed over from control to intervention, until August, 2017, when all clinics were implementing the intervention. Of 4898 individuals initiating PrEP (27 during the control period and 4871 during the intervention period), 2640 (54%) were women, the median age was 31 years (IQR 25-39), and 4092 (84%) reported having a partner living with HIV. The mean monthly number of PrEP initiations per clinic was 0·1 (SD 0·5) before the intervention and 7·5 (2·7) after intervention introduction (rate ratio 23·7, 95% CI 14·2-39·5, p<0·0001). PrEP continuation was 57% at 1 month, 44% at 3 months, and 34% at 6 months, and 12% of those who missed a refill returned later for PrEP re-initiation. Tenofovir diphosphate was detected in 68 (96%) of 71 blood samples collected from a randomly selected subset of participants. Six HIV infections were observed over 2531 person-years of observation (incidence 0·24 cases per 100 person-years), three of which occurred at the first visit after PrEP initiation.
Interpretation: We observed high uptake, reasonable continuation with high adherence, frequent PrEP restarts, and low HIV incidence. Integration of PrEP services within public HIV care clinics in Africa is feasible.
Funding: National Institute of Mental Health and Bill & Melinda Gates Foundation.
The Lancet. Global health · randomised controlled trial · 40 citationsread the source →
STAR*D: revising conventional wisdom.
The STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study used a series of sequenced, randomized treatment trials following a first and, if needed, subsequent treatment steps to define the tolerability and effectiveness of various options in both acute and longer term treatment. Adult outpatients (n=4041) with nonpsychotic major depressive disorder, substantial chronic and recurrent depression, and co-morbid psychiatric and general medical conditions were enrolled in 41 representative primary and specialty care settings. About one-third of participants remitted in first step treatment with citalopram, 50% of these within 6 weeks. Poorer outcomes were associated with minority status, socioeconomic disadvantage, more axis I and III co-morbid disorders, lower function and quality of life, and anxious and melancholic features. In step 2 medication switch, there were no significant differences in remission among within-class, out-of-class or dual-action agents: sertraline (27%), bupropion-sustained release (26%) and venlafaxine-extended release (25%). In step 2 medication augmentation of citalopram, there was no significant difference in remission between bupropion-sustained release (39%) and buspirone (33%), although participants using bupropion-sustained release had greater symptom reduction and better tolerability. There were no significant differences in remission in step 2 between cognitive therapy and medication treatment in either the switch (31% vs 27%) or augmentation (31% vs 33%) strategies, although participants in cognitive therapy augmentation had a longer time to remission than those in medication augmentation (55 vs 40 days). In step 3, there were no differences in remission between a switch to mirtazapine (8%) or nortriptyline (12%), or between augmentation with lithium (13%) or T(3) (triiodothyronine, liothyronine) [25%], although more participants discontinued lithium due to adverse effects than discontinued T(3). In the fourth step, there was no difference in remission between tranylcypromine (14%) or venlafaxine-extended release plus mirtazapine (16%), although the combination treatment had fewer adverse effects and had the advantages of not requiring a washout period or diet restrictions. Participants requiring more than two well delivered treatments may be characterized as treatment resistant given the substantially lower remission rates after that point. Treatment resistance was associated with more concurrent axis I or III co-morbid conditions, socioeconomic disadvantage, chronicity and melancholic or anxious features. However, if participants remained in treatment for up to four steps, about 67% reached remission. Times to remission were not substantially longer for later treatment steps. The importance of reaching remission is highlighted by the lower relapse rates in naturalistic follow-up for participants entering in remission compared with those entering with response but not remission (step 1: 34% vs 59%; step 2: 47% vs 68%; step 3: 42% vs 76%; step 4: 50% vs 83%). Clinical decision making based on the itemized measurement of symptoms and adverse effects at each treatment visit was feasible in STAR*D's real world settings and resulted in adequate dosages and durations of treatment that generally exceeded those typically found in practice settings. Although switch and augmentation strategies could not be directly compared due to the equipoise stratified randomized design, the higher remission rates at step 2 with medication augmentation are intriguing and merit further study.
CNS drugs · 236 citationsread the source →