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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 →

Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial.

Background: Treatment-resistant major depressive disorder is common; repetitive transcranial magnetic stimulation (rTMS) by use of high-frequency (10 Hz) left-side dorsolateral prefrontal cortex stimulation is an evidence-based treatment for this disorder. Intermittent theta burst stimulation (iTBS) is a newer form of rTMS that can be delivered in 3 min, versus 37·5 min for a standard 10 Hz treatment session. We aimed to establish the clinical effectiveness, safety, and tolerability of iTBS compared with standard 10 Hz rTMS in adults with treatment-resistant depression. Methods: In this randomised, multicentre, non-inferiority clinical trial, we recruited patients who were referred to specialty neurostimulation centres based at three Canadian university hospitals (Centre for Addiction and Mental Health and Toronto Western Hospital, Toronto, ON, and University of British Columbia Hospital, Vancouver, BC). Participants were aged 18-65 years, were diagnosed with a current treatment-resistant major depressive episode or could not tolerate at least two antidepressants in the current episode, were receiving stable antidepressant medication doses for at least 4 weeks before baseline, and had an HRSD-17 score of at least 18. Participants were randomly allocated (1:1) to treatment groups (10 Hz rTMS or iTBS) by use of a random permuted block method, with stratification by site and number of adequate trials in which the antidepressants were unsuccessful. Treatment was delivered open-label but investigators and outcome assessors were masked to treatment groups. Participants were treated with 10 Hz rTMS or iTBS to the left dorsolateral prefrontal cortex, administered on 5 days a week for 4-6 weeks. The primary outcome measure was change in 17-item Hamilton Rating Scale for Depression (HRSD-17) score, with a non-inferiority margin of 2·25 points. For the primary outcome measure, we did a per-protocol analysis of all participants who were randomly allocated to groups and who attained the primary completion point of 4 weeks. This trial is registered with ClinicalTrials.gov, number NCT01887782. Findings: Between Sept 3, 2013, and Oct 3, 2016, we randomly allocated 205 participants to receive 10 Hz rTMS and 209 participants to receive iTBS. 192 (94%) participants in the 10 Hz rTMS group and 193 (92%) in the iTBS group were assessed for the primary outcome after 4-6 weeks of treatment. HRSD-17 scores improved from 23·5 (SD 4·4) to 13·4 (7·8) in the 10 Hz rTMS group and from 23·6 (4·3) to 13·4 (7·9) in the iTBS group (adjusted difference 0·103 [corrected], lower 95% CI -1·16; p=0·0011), which indicated non-inferiority of iTBS. Self-rated intensity of pain associated with treatment was greater in the iTBS group than in the 10 Hz rTMS group (mean score on verbal analogue scale 3·8 [SD 2·0] vs 3·4 [2·0] out of 10; p=0·011). Dropout rates did not differ between groups (10 Hz rTMS: 13 [6%] of 205 participants; iTBS: 16 [8%] of 209 participants); p=0·6004). The most common treatment-related adverse event was headache in both groups (10 Hz rTMS: 131 [64%] of 204; iTBS: 136 [65%] of 208). Interpretation: In patients with treatment-resistant depression, iTBS was non-inferior to 10 Hz rTMS for the treatment of depression. Both treatments had low numbers of dropouts and similar side-effects, safety, and tolerability profiles. By use of iTBS, the number of patients treated per day with current rTMS devices can be increased several times without compromising clinical effectiveness. Funding: Canadian Institutes of Health Research.

Lancet (London, England) · randomised controlled trial · 938 citationsread the source →

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

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

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

Adverse childhood experiences and maternal anxiety and depression: a meta-analysis.

Background: It has been proposed that adverse childhood experiences (ACEs) can put women at risk for mental illness in the pregnancy and postpartum periods. While some studies have found strong support for this proposition, others have found weak or no support. This study is a meta-analysis of the association between ACEs and maternal mental health to resolve between-study discrepancies, and to examine potential moderators of associations. Methods: Three electronic databases (i.e., MEDLINE, Embase, and PsycINFO) were searched up to November 2018 by a health sciences librarian. A hand search was conducted in January 2020 and relevant studies were added. Included studies reported on associations between ACEs and maternal depression and/or anxiety in the perinatal period (pregnancy to 1-year postpartum). Pregnancy and postpartum outcomes were examined separately for both depression and anxiety. Random-effect meta-analyses were conducted. Moderator analyses were conducted using meta-regression. Study quality was evaluated using a 15-point scale. Results: The initial search yielded 4646 non-duplicate records and full text review occurred for 196 articles. A total of 15 studies (N = 7788) were included in the meta-analyses, of which 2 were also described narratively. Publication year ranged from 1998 to 2019. Mothers were approximately 28.93 years of age when they retrospectively reported on their ACEs. All studies had maternal self-report questionnaires for the mental health outcomes. Study quality ranged from 7 to 12. The pooled effect sizes between ACEs and prenatal (N = 12; r = .19; 95% CI= .13, .24) and postpartum (N = 7; r = .23; 95% CI = .06 to .39) depressive symptoms were significant. The pooled effect size between ACEs and prenatal anxiety was also significant (N = 5; r = .14; 95% CI= .07, .21). Moderator analyses indicated that timing of depressive and anxiety symptoms may be important for understanding associations. Conclusions: ACEs confer risk to maternal mental health, albeit effect sizes are small to moderate in magnitude. Trauma-informed approaches, as well as increased mental health support during and after pregnancy, may help to offset the relative risk of ACEs on maternal mental health.

BMC psychiatry · meta-analysis · 128 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 →

Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors.

Background: Persistent infection with high-risk human papillomaviruses (hrHPV) types is causally linked with the development of cervical precancer and cancer. HPV types 16 and 18 cause approximately 70% of cervical cancers worldwide. Objectives: To evaluate the harms and protection of prophylactic human papillomaviruses (HPV) vaccines against cervical precancer and HPV16/18 infection in adolescent girls and women. Search methods: We searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and Embase (June 2017) for reports on effects from trials. We searched trial registries and company results' registers to identify unpublished data for mortality and serious adverse events. Selection criteria: Randomised controlled trials comparing efficacy and safety in females offered HPV vaccines with placebo (vaccine adjuvants or another control vaccine). Data collection and analysis: We used Cochrane methodology and GRADE to rate the certainty of evidence for protection against cervical precancer (cervical intraepithelial neoplasia grade 2 and above [CIN2+], CIN grade 3 and above [CIN3+], and adenocarcinoma-in-situ [AIS]), and for harms. We distinguished between the effects of vaccines by participants' baseline HPV DNA status. The outcomes were precancer associated with vaccine HPV types and precancer irrespective of HPV type. Results are presented as risks in control and vaccination groups and risk ratios (RR) with 95% confidence intervals in brackets. Main results: We included 26 trials (73,428 participants). Ten trials, with follow-up of 1.3 to 8 years, addressed protection against CIN/AIS. Vaccine safety was evaluated over a period of 6 months to 7 years in 23 studies. Studies were not large enough or of sufficient duration to evaluate cervical cancer outcomes. All but one of the trials was funded by the vaccine manufacturers. We judged most included trials to be at low risk of bias. Studies involved monovalent (N = 1), bivalent (N = 18), and quadrivalent vaccines (N = 7). Most women were under 26 years of age. Three trials recruited women aged 25 and over. We summarize the effects of vaccines in participants who had at least one immunisation. Efficacy endpoints by initial HPV DNA statushrHPV negativeHPV vaccines reduce CIN2+, CIN3+, AIS associated with HPV16/18 compared with placebo in adolescent girls and women aged 15 to 26. There is high-certainty evidence that vaccines lower CIN2+ from 164 to 2/10,000 (RR 0.01 (0 to 0.05)) and CIN3+ from 70 to 0/10,000 (RR 0.01 (0.00 to 0.10). There is moderate-certainty evidence that vaccines reduce the risk of AIS from 9 to 0/10,000 (RR 0.10 (0.01 to 0.82).HPV vaccines reduce the risk of any CIN2+ from 287 to 106/10,000 (RR 0.37 (0.25 to 0.55), high certainty) and probably reduce any AIS lesions from 10 to 0/10,000 (RR 0.1 (0.01 to 0.76), moderate certainty). The size of reduction in CIN3+ with vaccines differed between bivalent and quadrivalent vaccines (bivalent: RR 0.08 (0.03 to 0.23), high certainty; quadrivalent: RR 0.54 (0.36 to 0.82), moderate certainty). Data in older women were not available for this comparison.HPV16/18 negativeIn those aged 15 to 26 years, vaccines reduce CIN2+ associated with HPV16/18 from 113 to 6 /10,000 (RR 0.05 (0.03 to 0.10). In women 24 years or older the absolute and relative reduction in the risk of these lesions is smaller (from 45 to 14/10,000, (RR 0.30 (0.11 to 0.81), moderate certainty). HPV vaccines reduce the risk of CIN3+ and AIS associated with HPV16/18 in younger women (RR 0.05 (0.02 to 0.14), high certainty and RR 0.09 (0.01 to 0.72), moderate certainty, respectively). No trials in older women have measured these outcomes. Vaccines reduce any CIN2+ from 231 to 95/10,000, (RR 0.41 (0.32 to 0.52)) in younger women. No data are reported for more severe lesions. Regardless of HPV DNA statusIn younger women HPV vaccines reduce the risk of CIN2+ associated with HPV16/18 from 341 to 157/10,000 (RR 0.46 (0.37 to 0.57), high certainty). Similar reductions in risk were observed for CIN3+ associated with HPV16/18 (high certainty). The number of women with AIS associated with HPV16/18 is reduced from 14 to 5/10,000 with HPV vaccines (high certainty).HPV vaccines reduce any CIN2+ from 559 to 391/10,000 (RR 0.70 (0.58 to 0.85, high certainty) and any AIS from 17 to 5/10,000 (RR 0.32 (0.15 to 0.67), high certainty). The reduction in any CIN3+ differed by vaccine type (bivalent vaccine: RR 0.55 (0.43 to 0.71) and quadrivalent vaccine: RR 0.81 (0.69 to 0.96)).In women vaccinated at 24 to 45 years of age, there is moderate-certainty evidence that the risks of CIN2+ associated with HPV16/18 and any CIN2+ are similar between vaccinated and unvaccinated women (RR 0.74 (0.52 to 1.05) and RR 1.04 (0.83 to 1.30) respectively). No data are reported in this age group for CIN3+ or AIS.Adverse effectsThe risk of serious adverse events is similar between control and HPV vaccines in women of all ages (669 versus 656/10,000, RR 0.98 (0.92 to 1.05), high certainty). Mortality was 11/10,000 in control groups compared with 14/10,000 (9 to 22) with HPV vaccine (RR 1.29 [0.85 to 1.98]; low certainty). The number of deaths was low overall but there is a higher number of deaths in older women. No pattern in the cause or timing of death has been established. Pregnancy outcomesAmong those who became pregnant during the studies, we did not find an increased risk of miscarriage (1618 versus 1424/10,000, RR 0.88 (0.68 to 1.14), high certainty) or termination (931 versus 838/10,000 RR 0.90 (0.80 to 1.02), high certainty). The effects on congenital abnormalities and stillbirths are uncertain (RR 1.22 (0.88 to 1.69), moderate certainty and (RR 1.12 (0.68 to 1.83), moderate certainty, respectively). Authors' conclusions: There is high-certainty evidence that HPV vaccines protect against cervical precancer in adolescent girls and young women aged 15 to 26. The effect is higher for lesions associated with HPV16/18 than for lesions irrespective of HPV type. The effect is greater in those who are negative for hrHPV or HPV16/18 DNA at enrolment than those unselected for HPV DNA status. There is moderate-certainty evidence that HPV vaccines reduce CIN2+ in older women who are HPV16/18 negative, but not when they are unselected by HPV DNA status. We did not find an increased risk of serious adverse effects. Although the number of deaths is low overall, there were more deaths among women older than 25 years who received the vaccine. The deaths reported in the studies have been judged not to be related to the vaccine. Increased risk of adverse pregnancy outcomes after HPV vaccination cannot be excluded, although the risk of miscarriage and termination are similar between trial arms. Long-term of follow-up is needed to monitor the impact on cervical cancer, occurrence of rare harms and pregnancy outcomes.

The Cochrane database of systematic reviews · systematic review · 290 citationsread the source →

Guided graded exercise self-help plus specialist medical care versus specialist medical care alone for chronic fatigue syndrome (GETSET): a pragmatic randomised controlled trial.

Background: Graded exercise therapy is an effective and safe treatment for chronic fatigue syndrome, but it is therapist intensive and availability is limited. We aimed to test the efficacy and safety of graded exercise delivered as guided self-help. Methods: In this pragmatic randomised controlled trial, we recruited adult patients (18 years and older) who met the UK National Institute for Health and Care Excellence criteria for chronic fatigue syndrome from two secondary-care clinics in the UK. Patients were randomly assigned to receive specialist medical care (SMC) alone (control group) or SMC with additional guided graded exercise self-help (GES). Block randomisation (randomly varying block sizes) was done at the level of the individual with a computer-generated sequence and was stratified by centre, depression score, and severity of physical disability. Patients and physiotherapists were necessarily unmasked from intervention assignment; the statistician was masked from intervention assignment. SMC was delivered by specialist doctors but was not standardised; GES consisted of a self-help booklet describing a six-step graded exercise programme that would take roughly 12 weeks to complete, and up to four guidance sessions with a physiotherapist over 8 weeks (maximum 90 min in total). Primary outcomes were fatigue (measured by the Chalder Fatigue Questionnaire) and physical function (assessed by the Short Form-36 physical function subscale); both were self-rated by patients at 12 weeks after randomisation and analysed in all randomised patients with outcome data at follow-up (ie, by modified intention to treat). We recorded adverse events, including serious adverse reactions to trial interventions. We used multiple linear regression analysis to compare SMC with GES, adjusting for baseline and stratification factors. This trial is registered at ISRCTN, number ISRCTN22975026. Findings: Between May 15, 2012, and Dec 24, 2014, we recruited 211 eligible patients, of whom 107 were assigned to the GES group and 104 to the control group. At 12 weeks, compared with the control group, mean fatigue score was 19·1 (SD 7·6) in the GES group and 22·9 (6·9) in the control group (adjusted difference -4·2 points, 95% CI -6·1 to -2·3, p<0·0001; effect size 0·53) and mean physical function score was 55·7 (23·3) in the GES group and 50·8 (25·3) in the control group (adjusted difference 6·3 points, 1·8 to 10·8, p=0·006; 0·20). No serious adverse reactions were recorded and other safety measures did not differ between the groups, after allowing for missing data. Interpretation: GES is a safe intervention that might reduce fatigue and, to a lesser extent, physical disability for patients with chronic fatigue syndrome. These findings need confirmation and extension to other health-care settings. Funding: UK National Institute for Health Research Research for Patient Benefit Programme and the Sue Estermann Fund.

Lancet (London, England) · randomised controlled trial · 44 citationsread the source →

Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial.

Background: Systemic relapses remain a major problem in locally advanced rectal cancer. Using short-course radiotherapy followed by chemotherapy and delayed surgery, the Rectal cancer And Preoperative Induction therapy followed by Dedicated Operation (RAPIDO) trial aimed to reduce distant metastases without compromising locoregional control. Methods: In this multicentre, open-label, randomised, controlled, phase 3 trial, participants were recruited from 54 centres in the Netherlands, Sweden, Spain, Slovenia, Denmark, Norway, and the USA. Patients were eligible if they were aged 18 years or older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, had a biopsy-proven, newly diagnosed, primary, locally advanced rectal adenocarcinoma, which was classified as high risk on pelvic MRI (with at least one of the following criteria: clinical tumour [cT] stage cT4a or cT4b, extramural vascular invasion, clinical nodal [cN] stage cN2, involved mesorectal fascia, or enlarged lateral lymph nodes), were mentally and physically fit for chemotherapy, and could be assessed for staging within 5 weeks before randomisation. Eligible participants were randomly assigned (1:1), using a management system with a randomly varying block design (each block size randomly chosen to contain two to four allocations), stratified by centre, ECOG performance status, cT stage, and cN stage, to either the experimental or standard of care group. All investigators remained masked for the primary endpoint until a prespecified number of events was reached. Patients allocated to the experimental treatment group received short-course radiotherapy (5 × 5 Gy over a maximum of 8 days) followed by six cycles of CAPOX chemotherapy (capecitabine 1000 mg/m2 orally twice daily on days 1-14, oxaliplatin 130 mg/m2 intravenously on day 1, and a chemotherapy-free interval between days 15-21) or nine cycles of FOLFOX4 (oxaliplatin 85 mg/m2 intravenously on day 1, leucovorin [folinic acid] 200 mg/m2 intravenously on days 1 and 2, followed by bolus fluorouracil 400 mg/m2 intravenously and fluorouracil 600 mg/m2 intravenously for 22 h on days 1 and 2, and a chemotherapy-free interval between days 3-14) followed by total mesorectal excision. Choice of CAPOX or FOLFOX4 was per physician discretion or hospital policy. Patients allocated to the standard of care group received 28 daily fractions of 1·8 Gy up to 50·4 Gy or 25 fractions of 2·0 Gy up to 50·0 Gy (per physician discretion or hospital policy), with concomitant twice-daily oral capecitabine 825 mg/m2 followed by total mesorectal excision and, if stipulated by hospital policy, adjuvant chemotherapy with eight cycles of CAPOX or 12 cycles of FOLFOX4. The primary endpoint was 3-year disease-related treatment failure, defined as the first occurrence of locoregional failure, distant metastasis, new primary colorectal tumour, or treatment-related death, assessed in the intention-to-treat population. Safety was assessed by intention to treat. This study is registered with the EudraCT, 2010-023957-12, and ClinicalTrials.gov, NCT01558921, and is now complete. Findings: Between June 21, 2011, and June 2, 2016, 920 patients were enrolled and randomly assigned to a treatment, of whom 912 were eligible (462 in the experimental group; 450 in the standard of care group). Median follow-up was 4·6 years (IQR 3·5-5·5). At 3 years after randomisation, the cumulative probability of disease-related treatment failure was 23·7% (95% CI 19·8-27·6) in the experimental group versus 30·4% (26·1-34·6) in the standard of care group (hazard ratio 0·75, 95% CI 0·60-0·95; p=0·019). The most common grade 3 or higher adverse event during preoperative therapy in both groups was diarrhoea (81 [18%] of 460 patients in the experimental group and 41 [9%] of 441 in the standard of care group) and neurological toxicity during adjuvant chemotherapy in the standard of care group (16 [9%] of 187 patients). Serious adverse events occurred in 177 (38%) of 460 participants in the experimental group and, in the standard of care group, in 87 (34%) of 254 patients without adjuvant chemotherapy and in 64 (34%) of 187 with adjuvant chemotherapy. Treatment-related deaths occurred in four participants in the experimental group (one cardiac arrest, one pulmonary embolism, two infectious complications) and in four participants in the standard of care group (one pulmonary embolism, one neutropenic sepsis, one aspiration, one suicide due to severe depression). Interpretation: The observed decreased probability of disease-related treatment failure in the experimental group is probably indicative of the increased efficacy of preoperative chemotherapy as opposed to adjuvant chemotherapy in this setting. Therefore, the experimental treatment can be considered as a new standard of care in high-risk locally advanced rectal cancer. Funding: Dutch Cancer Foundation, Swedish Cancer Society, Spanish Ministry of Economy and Competitiveness, and Spanish Clinical Research Network.

The Lancet. Oncology · randomised controlled trial · 1212 citationsread the source →

Designing and developing a nature-based virtual reality with heart rate variability biofeedback for surgical anxiety and pain management: evidence from total knee arthroplasty patients.

Objectives: Total knee arthroplasty (TKA) is one of the most common joint surgeries, with over a million procedures performed annually in the US. Over 70% of patients report moderate to high pain and anxiety surrounding TKA surgery, and 96% are discharged with an opioid prescription. This population requires special attention as approximately 90% of TKA patients are older adults and one of the riskiest groups prone to misusing opioids. This study aimed to develop and compare the efficacy of nature-based virtual reality (VR) with heart rate variability biofeedback (HRVBF) to mitigate surgical pain and anxiety. Methods: This randomized control trial recruited 30 patients (mean age = 66.3 ± 8.2 years, 23 F, 7 M) undergoing TKA surgery and randomly assigned to a control, 2D video with HRVBF, or VR with HRVBF group. A visual analog scale (VAS) was used to measure pain levels before and after the intervention. In addition, a second VAS and the State-Trait Anxiety Inventory (STAI) were used to measure anxiety before and after the intervention. Electrocardiogram (ECG) was used to continuously measure HRV and respiration rate in preoperative and postoperative settings. Results: VR and 2D-video with HRVBF decreased pain and anxiety post-intervention compared with the control group, p's <.01. On analyzing physiological signals, both treatment groups showed greater parasympathetic activity levels, and VR with HRVBF reduced pain more than the 2D video, p < .01. Conclusions: Nature-based VR and 2D video with HRVBF can mitigate surgical pain and anxiety. However, VR may be more efficacious than 2D video in reducing pain.

Aging & mental health · randomised controlled trial · 17 citationsread the source →

Benefits of Early Versus Delayed Palliative Care to Informal Family Caregivers of Patients With Advanced Cancer: Outcomes From the ENABLE III Randomized Controlled Trial.

Purpose: To determine the effect of early versus delayed initiation of a palliative care intervention for family caregivers (CGs) of patients with advanced cancer. Patients and methods: Between October 2010 and March 2013, CGs of patients with advanced cancer were randomly assigned to receive three structured weekly telephone coaching sessions, monthly follow-up, and a bereavement call either early after enrollment or 3 months later. CGs of patients with advanced cancer were recruited from a National Cancer Institute cancer center, a Veterans Administration Medical Center, and two community outreach clinics. Outcomes were quality of life (QOL), depression, and burden (objective, stress, and demand). Results: A total of 122 CGs (early, n = 61; delayed, n = 61) of 207 patients participated; average age was 60 years, and most were female (78.7%) and white (92.6%). Between-group differences in depression scores from enrollment to 3 months (before delayed group started intervention) favored the early group (mean difference, -3.4; SE, 1.5; d = -.32; P = .02). There were no differences in QOL (mean difference, -2; SE, 2.3; d = -.13; P = .39) or burden (objective: mean difference, 0.3; SE, .7; d = .09; P = .64; stress: mean difference, -.5; SE, .5; d = -.2; P = .29; demand: mean difference, 0; SE, .7; d = -.01; P = .97). In decedents' CGs, a terminal decline analysis indicated between-group differences favoring the early group for depression (mean difference, -3.8; SE, 1.5; d = -.39; P = .02) and stress burden (mean difference, -1.1; SE, .4; d = -.44; P = .01) but not for QOL (mean difference, -4.9; SE, 2.6; d = -.3; P = .07), objective burden (mean difference, -.6; SE, .6; d = -.18; P = .27), or demand burden (mean difference, -.7; SE, .6; d = -.23; P = .22). Conclusion: Early-group CGs had lower depression scores at 3 months and lower depression and stress burden in the terminal decline analysis. Palliative care for CGs should be initiated as early as possible to maximize benefits.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology · randomised controlled trial · 342 citationsread the source →

Evaluation of the effectiveness of a home-based inspiratory muscle training programme in patients with chronic obstructive pulmonary disease using multiple inspiratory muscle tests.

Purpose: To evaluate the effectiveness of a home-based inspiratory muscle training (IMT) programme using multiple inspiratory muscle tests. Method: Sixty-eight patients (37 M) with moderate to severe chronic obstructive pulmonary disease (COPD) (Mean [SD], FEV1 36.1 [13.6]% pred.; FEV1/FVC 35.7 [11.2]%) were randomised into an experimental or control group and trained with a threshold loading device at intensity >30% maximum inspiratory pressure (PImax) or <15% PImax, respectively, for 7 weeks. Thirty-nine patients (23 M) completed the study. The following measures were assessed pre- and post-IMT: PImax, sniff inspiratory nasal pressure (SNIP), diaphragm contractility (Pdi,tw), incremental shuttle walk test (ISWT), respiratory muscle endurance (RME), chronic respiratory disease questionnaire (CRDQ), the hospital anxiety and depression scale (HADS) and the SF-36. Between-group changes were assessed using one-way analysis of variance (ANOVA). Results: PImax and perception of well-being improved significantly post-IMT [p = 0.04 and <0.05 in four domains, respectively]. This was not reflected in SNIP [p = 0.7], Pdi,tw [p = 0.8], RME [p = 0.9] or ISWT [p = 0.5]. Conclusions: A seven-week, community-based IMT programme, with realistic use of health-care resources, improves PImax and perception of well-being but a different design may be required for improvement in other measures. Multiple tests provide a more comprehensive evaluation of changes in muscle function post-IMT. Implications for rehabilitation: A seven-week, home-based inspiratory muscle training programme improves maximal inspiratory pressure and perception of well-being in patients with moderate to severe COPD but not sniff nasal inspiratory pressure or diaphragm contractility, respiratory muscle endurance and exercise capacity. Multiple tests are recommended for a more comprehensive assessment of changes in muscle function following inspiratory muscle training programmes. Therapists need to explore different community-based inspiratory muscle training regimes for COPD patients and identify the optimal exercise protocol that is likely to lead to improvements in diaphragm contractility and exercise capacity.

Disability and rehabilitation · randomised controlled trial · 28 citationsread the source →

Labor migration and HIV risk: a systematic review of the literature.

To inform the development of multilevel strategies for addressing HIV risk among labor migrants, 97 articles from the health and social science literatures were systematically reviewed. The study locations were Africa (23 %), the Americas (26 %), Europe (7 %), South East Asia (21 %), and Western Pacific (24 %). Among the studies meeting inclusion criteria, HIV risk was associated with multilevel determinants at the levels of policy, sociocultural context, health and mental health, and sexual practices. The policy determinants most often associated with HIV risk were: prolonged and/or frequent absence, financial status, and difficult working and housing conditions. The sociocultural context determinants most often associated with HIV risk were: cultural norms, family separation, and low social support. The health and mental health factors most often associated with HIV risk were: substance use, other STIs, mental health problems, no HIV testing, and needle use. The sexual practices most often associated with increased HIV risk were: limited condom use, multiple partnering, clients of sex workers, low HIV knowledge, and low perceived HIV risk. Magnitude of effects through multivariate statistics were demonstrated more for health and mental health and sexual practices, than for policy or sociocultural context. The consistency of these findings across multiple diverse global labor migration sites underlines the need for multilevel intervention strategies. However, to better inform the development, implementation, and evaluation of multilevel interventions, additional research is needed that overcomes prior methodological limitations and focuses on building new contextually tailored interventions and policies.

AIDS and behavior · systematic review · 172 citationsread the source →

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

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

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

Female sexual dysfunction, sexual distress, and compatibility with partner.

Introduction: Few studies have looked at prevalence estimates for female sexual dysfunctions in combination with personal distress, although existing diagnostic criteria for sexual disorders include both aspects. Further, the variation in female sexual function has been shown to be largely explained by unique nongenetic factors. Such factors may include partner sexual function and perception of sexual compatibility with a partner, factors which may also be associated with sexual distress. Aim: We investigated the association between female sexual dysfunction and distress as well as their association with partner compatibility. Methods: In order to assess sexual function and distress, the Female Sexual Function Index and seven items from the Female Sexual Distress Scale were used in a population-based sample of 5,463 women, aged 18-49 years. The women were, based on cutoff points, classified as either having neither dysfunction nor distress, one of them, or both, separately for each dysfunction. Further, the associations between partner compatibility, distress, and sexual dysfunctions were analyzed. Sexual compatibility with partner was investigated by using several items exploring, for example, amount of foreplay, interest in sex, and communication about sexual matters. Main outcome measures: Associations between partner compatibility and female sexual function and sexual distress. Results: The proportion of women reporting both sexual dysfunction and distress ranged from 7% to 23%, depending on the dysfunction. Desire disorders followed by orgasmic disorders were most common. All compatibility variables were significantly associated with distress and with most of the sexual dysfunctions. The main complaints of the women were "too little foreplay" (42%) and "partner is more interested" (35%). The women feeling distress or having a sexual dysfunction reported more incompatibility with partner compared with functional women. Conclusions: The findings highlight the importance of addressing partner compatibility for successful treatment and counseling of female sexual dysfunctions.

The journal of sexual medicine · cohort or longitudinal · 122 citationsread the source →

Parental education and inequalities in child mortality: a global systematic review and meta-analysis.

Background: The educational attainment of parents, particularly mothers, has been associated with lower levels of child mortality, yet there is no consensus on the magnitude of this relationship globally. We aimed to estimate the total reductions in under-5 mortality that are associated with increased maternal and paternal education, during distinct age intervals. Methods: This study is a comprehensive global systematic review and meta-analysis of all existing studies of the effects of parental education on neonatal, infant, and under-5 child mortality, combined with primary analyses of Demographic and Health Survey (DHS) data. The literature search of seven databases (CINAHL, Embase, MEDLINE, PsycINFO, PubMed, Scopus, and Web of Science) was done between Jan 23 and Feb 8, 2019, and updated on Jan 7, 2021, with no language or publication date restrictions. Teams of independent reviewers assessed each record for its inclusion of individual-level data on parental education and child mortality and excluded articles on the basis of study design and availability of relevant statistics. Full-text screening was done in 15 languages. Data extracted from these studies were combined with primary microdata from the DHS for meta-analyses relating maternal or paternal education with mortality at six age intervals: 0-27 days, 1-11 months, 1-4 years, 0-4 years, 0-11 months, and 1 month to 4 years. Novel mixed-effects meta-regression models were implemented to address heterogeneity in referent and exposure measures among the studies and to adjust for study-level covariates (wealth or income, partner's years of schooling, and sex of the child). This study was registered with PROSPERO (CRD42020141731). Findings: The systematic review returned 5339 unique records, yielding 186 included studies after exclusions. DHS data were compiled from 114 unique surveys, capturing 3 112 474 livebirths. Data extracted from the systematic review were synthesized together with primary DHS data, for meta-analysis on a total of 300 studies from 92 countries. Both increased maternal and paternal education showed a dose-response relationship linked to reduced under-5 mortality, with maternal education emerging as a stronger predictor. We observed a reduction in under-5 mortality of 31·0% (95% CI 29·0-32·6) for children born to mothers with 12 years of education (ie, completed secondary education) and 17·3% (15·0-18·8) for children born to fathers with 12 years of education, compared with those born to a parent with no education. We also showed that a single additional year of schooling was, on average, associated with a reduction in under-5 mortality of 3·04% (2·82-3·23) for maternal education and 1·57% (1·35-1·72) for paternal education. The association between higher parental education and lower child mortality was significant for both parents at all ages studied and was largest after the first month of life. The meta-analysis framework incorporated uncertainty associated with each individual effect size into the model fitting process, in an effort to decrease the risk of bias introduced by study design and quality. Interpretation: To our knowledge, this study is the first effort to systematically quantify the transgenerational importance of education for child survival at the global level. The results showed that lower maternal and paternal education are both risk factors for child mortality, even after controlling for other markers of family socioeconomic status. This study provides robust evidence for universal quality education as a mechanism to achieve the Sustainable Development Goal target 3.2 of reducing neonatal and child mortality. Funding: Research Council of Norway, Bill & Melinda Gates Foundation, and Rockefeller Foundation-Boston University Commission on Social Determinants, Data, and Decision Making (3-D Commission).

Lancet (London, England) · meta-analysis · 132 citationsread the source →

Moral Injury, Chaplaincy and Mental Health Provider Approaches to Treatment: A Scoping Review.

The aim of this research was to describe the evidence examining the approaches taken by mental health providers (MHPs) and chaplains to address symptoms related to moral injury (MI) or exposure to potentially morally injurious events (PMIEs). This research also considers the implications for a holistic approach to address symptoms related to MI that combines mental health and chaplaincy work. A scoping review of literature was conducted using Medline, PsycINFO, Embase, Central Register of Controlled Trials, Proquest, Philosphers Index, CINAHL, SocINDEX, Academic Search Complete, Web of Science and Scopus databases using search terms related to MI and chaplaincy approaches or psychological approaches to MI. The search identified 35 eligible studies: 26 quantitative studies and nine qualitative studies. Most quantitative studies (n = 33) were conducted in military samples. The studies examined interventions delivered by chaplains (n = 5), MHPs (n = 23) and combined approaches (n = 7). Most studies used symptoms of post-traumatic stress disorder (PTSD) and/or depression as primary outcomes. Various approaches to addressing MI have been reported in the literature, including MHP, chaplaincy and combined approaches, however, there is currently limited evidence to support the effectiveness of any approach. There is a need for high quality empirical studies assessing the effectiveness of interventions designed to address MI-related symptoms. Outcome measures should include the breadth of psychosocial and spiritual impacts of MI if we are to establish the benefits of MHP and chaplaincy approaches and the potential incremental value of combining both approaches into a holistic model of care.

Journal of religion and health · review · 25 citationsread the source →

Mobile Apps and Quality of Life in Patients With Breast Cancer and Survivors: Systematic Literature Review.

Background: Side effects of breast cancer treatment may persist long into survivorship, reducing quality of life (QOL) in patients with breast cancer and survivors. There is growing evidence for the use of digital health technologies, such as mobile apps, to support self-management, decrease symptom burden, and improve QOL in patients with cancer. However, an updated overview of the effects of mobile apps on QOL and well-being in patients with breast cancer and survivors is needed. Objective: The aim of this review was to provide an overview of breast cancer-specific, mobile app-driven lifestyle or behavioral interventions in patient care through to survivorship and their impact on QOL and mental well-being. Methods: A systematic search of PubMed, Scopus, and Web of Science was conducted to identify relevant studies. The inclusion criteria were limited to original studies involving a trial of a mobile app-driven lifestyle or behavioral intervention for patients with breast cancer or survivors and using QOL or well-being measures. The results of the studies that met the inclusion criterion were then synthesized in text and table format. The quality of the evidence was assessed with the Cochrane risk-of-bias tool. Results: A total of 17 studies with the number of participants ranging from 23 to 356 met the inclusion criterion. Of the 17 reviewed studies, 7 (41%) delivered an app-only intervention, and 10 (59%) combined an app with additional supporting materials, such as SMS text messaging, telecoaching, wearables, or printed materials. Among the 17 reviewed studies, 6 (35%) focused on aiding patients with breast cancer during the active treatment phase (excluding ongoing hormone therapy), whereas the remaining 11 (65%) focused on survivorship. The majority of the studies (14/17, 82%) observed some positive effects on QOL or well-being measures. Conclusions: The results of the review indicate that mobile apps are a promising avenue for improving QOL and well-being in breast cancer care. Positive effects were observed in patients undergoing active treatment in all reviewed studies, but effects were less clear after chemotherapy and in long-term survivors. Although lifestyle and behavioral digital interventions are still being developed, and further research should still be pursued, the available data suggest that current mobile health apps aid patients with breast cancer and survivors.

Journal of medical Internet research · systematic review · 47 citationsread the source →

Review: Assessment, development, and treatment of childhood perfectionism: a systematic review.

Background: In the adult literature, perfectionism has been linked with psychopathology and poor treatment outcomes, leading to perfectionism-focussed therapies. The child and adolescent perfectionism literature is comparatively sparse. Method: A systematic search of five electronic databases (Web of Knowledge, APA PsycNET, PubMed, ERIC/ProQuest, and Scopus) was conducted to identify studies of perfectionism in children and adolescents, in the context of psychopathology. Results: The search identified 133 studies, 84 of which discussed perfectionism as a correlate of mental health problems. These studies were briefly synthesised, with the systematic review focussing on evaluating papers on the development (n = 23), assessment (n = 19), and treatment (n = 7) of perfectionism. Conclusion: Treatment studies did not reflect the phenomenology of perfectionism found in this review.

Child and adolescent mental health · review · 22 citationsread the source →

Social Participation Among Older Adults Before and After Long-Term Care Facility Entry.

Importance: Social participation is essential throughout life and is associated with decreased mortality and increased quality of life. It is unknown whether long-term care facility (LTCF) entry disrupts or facilitates it. Objectives: To determine longitudinal trends in social participation before and after entry into nursing homes (NHs) and assisted living facilities (ALs) and to explore factors associated with participation. Design, setting, and participants: This nationally representative longitudinal cohort study using prospectively collected annual data from the US National Health and Aging Trends Study from 2011 to 2019 included community-dwelling Medicare beneficiaries entering LTCFs. Interviews conducted 4 years before and 2 years after NH or AL entry (index date) were included. Data analysis was performed from September 16, 2022, to May 25, 2025. Main outcomes and measures: Two categories of social participation comprising 5 activities were assessed: socialization (visiting with friends or family and going out for enjoyment) and community participation (attending religious services, participating in clubs or other organized activities, and volunteering). Participation over time was modeled using linear splines before, upon, and after LTCF entry. Modified Poisson regressions were used to explore associations with maintaining and starting activities, adjusted for age, sex, race and ethnicity, and proxy response were used. Results: The total sample included 606 LTCF entrants (weighted mean [SD] age 85 [7.4] years, 404 female [66% weighted]), of whom 104 individuals were Black (7%), 23 Hispanic (4%), 464 White (86%); and 15 of any other race and ethnicity (3%). Before entry, social participation decreased in all activities (-4.7 to -2.0% annually). Of the total, 275 (44%) entered a NH and 331 (56%) entered an AL facility. Upon entry, going out for enjoyment decreased (-14.1%), but club participation and religious attendance increased (15.6% and 12.6%, respectively). Before LTCF entry, social participation decreased in all activities (-4.7 to -2.0% annually). After entry, going out for enjoyment decreased (-14.1%), but club participation and religious attendance (12.6%) increased (15.6% and 12.6%, respectively). In exploratory analyses, women were more likely to maintain visits (adjust risk ratio [aRR], 1.3; 95% CI, 1.1-1.5) and start attending religious services (aRR, 1.6; 95% CI, 1.0-2.8). NH residents were less likely to go out for enjoyment (aRR, 0.6; 95% CI, 0.5-0.8 for maintaining; aRR, 0.6; 95% CI, 0.4-1.0 for starting) and keep attending religious services (aRR, 0.7; 95% CI, 0.6-0.9). Black, Hispanic, and residents of other race or ethnicity were much less likely to start going out for enjoyment (aRR, 0.3; 95% CI, 0.1-0.8). Conclusions and relevance: This cohort study found that LTCF entry generally promoted community participation and reduced socialization. Benefits may be less likely among men, NH entrants, and residents of racial and ethnic minority groups.

JAMA internal medicine · 4 citationsread the source →

Familial Factors in the Development of Social Anxiety Disorder.

The purpose of the current article is to explore familial factors that influence the development of social anxiety disorder (SAD) in children and adolescents, including parenting, sibling relationships, and family environment. A multitude of interrelated genetic and familial factors have been found to cause and maintain SAD in children and adolescents. There are many challenges in diagnosing and treating the disorder. Knowledge and awareness of familial factors provide insight on targeted treatments that prevent or ameliorate SAD. [Journal of Psychosocial Nursing and Mental Health Services, 59(7), 23-34.].

Journal of psychosocial nursing and mental health services · 4 citationsread the source →

Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.

Background: Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods: We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings: In 2019, there were 12·2 million (95% UI 11·0-13·6) incident cases of stroke, 101 million (93·2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6·55 million (6·00-7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8-12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1-6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0-73·0), prevalent strokes increased by 85·0% (83·0-88·0), deaths from stroke increased by 43·0% (31·0-55·0), and DALYs due to stroke increased by 32·0% (22·0-42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0-18·0), mortality decreased by 36·0% (31·0-42·0), prevalence decreased by 6·0% (5·0-7·0), and DALYs decreased by 36·0% (31·0-42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0-24·0) and incidence rates increased by 15·0% (12·0-18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5-3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5-3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57-8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97-3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01-1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7-90·8] DALYs or 55·5% [48·2-62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3-48·6] DALYs or 24·3% [15·7-33·2]), high fasting plasma glucose (28·9 million [19·8-41·5] DALYs or 20·2% [13·8-29·1]), ambient particulate matter pollution (28·7 million [23·4-33·4] DALYs or 20·1% [16·6-23·0]), and smoking (25·3 million [22·6-28·2] DALYs or 17·6% [16·4-19·0]). Interpretation: The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Funding: Bill & Melinda Gates Foundation.

The Lancet. Neurology · 5441 citationsread the source →

Clinical and cost-effectiveness of cognitive behaviour therapy for health anxiety in medical patients: a multicentre randomised controlled trial.

Background: Health anxiety has been treated by therapists expert in cognitive behaviour therapy with some specific benefit in some patients referred to psychological services. Those in hospital care have been less often investigated. Following a pilot trial suggesting efficacy we carried out a randomised study in hospital medical clinics. Methods: We undertook a multicentre, randomised trial on health anxious patients attending cardiac, endocrine, gastroenterological, neurological, and respiratory medicine clinics in secondary care. We included those aged 16-75 years, who satisfied the criteria for excessive health anxiety, and were resident in the area covered by the hospital, were not under investigation for new pathology or too medically unwell to take part. We used a computer-generated random scheme to allocate eligible medical patients to an active treatment group of five-to-ten sessions of adapted cognitive behaviour therapy (CBT-HA group) delivered by hospital-based therapists or to standard care in the clinics. The primary outcome was change in health anxiety symptoms measured by the Health Anxiety Inventory at 1 year and the main secondary hypothesis was equivalence of total health and social care costs over 2 years, with an equivalence margin of £150. Analysis was by intention to treat. The study is registered with controlled-trials.com, ISRCTN14565822. Findings: Of 28,991 patients screened, 444 were randomly assigned to receive either adapted cognitive behaviour therapy (CBT-HA group, 219 participants) or standard care (standard care group, 225), with 205 participants in the CBT-HA group and 212 in the standard care group included in the analyses of the primary endpoints. At 1 year, improvement in health anxiety in the patients in the CBT-HA group was 2·98 points greater than in those in the standard care group (95% CI 1·64-4·33, p<0·0001), and twice as many patients receiving cognitive behaviour therapy achieved normal levels of health anxiety compared with those in the control group (13·9% vs 7·3%; odds ratio 2·15, 95% CI 1·09-4·23, p=0·0273). Similar differences were observed at 6 months and 2 years, and there were concomitant reductions in generalised anxiety and, to a lesser extent, depression. Of nine deaths, six were in the control group; all were due to pre-existing illness. Social functioning or health-related quality of life did not differ significantly between groups. Equivalence in total 2-year costs was not achieved, but the difference was not significant (adjusted mean difference £156, 95% CI -1446 to 1758, p=0·848). Interpretation: This form of adapted cognitive behaviour therapy for health anxiety led to sustained symptomatic benefit over 2 years, with no significant effect on total costs. It deserves wider application in medical care. Funding: National Institute for Health Research Health Technology Assessment Programme.

Lancet (London, England) · randomised controlled trial · 96 citationsread the source →

Resilience under conditions of extreme stress: a multilevel perspective

From the perspective of developmental psychopathology, maladaptation and mental disorder are viewed as evolving from progressive liabilities in the organization of biological and psychological systems, resulting in the undermining of the individual's efforts to adapt effectively to stressful and adverse experiences 1,2. The dynamic interplay between risk and protective forces is conceived as influencing the developmental course through the impact it has on the quality of the organization of biological and psychological systems as the individual develops 3. Developmental psychopathologists stress that there is multifinality in developmental processes such that the manner in which persons respond to and interact with vulnerability and protective factors at each level of the ecology (i.e., culture, community, family, and their transactions) allows for diversity in developmental outcomes 4,5. Individuals may begin on the same major developmental trajectory, yet exhibit very different patterns of maladaptation or adaptation. The pathway to either psychopathology or resilience is influenced by a complex matrix of the individual's level of biological and psychological organization, current experiences, active choices, the social context, timing of the adverse event(s) and experiences, and the developmental history of the individual 5. Understanding the dynamic transactions between risk and protective factors plays a central role in building developmentally informed models of prevention. Through increasing the relative balance of protective processes over risk factors, the potential for righting the developmental course, attaining adaptive developmental pathways, and reducing the emergence of psychopathology may be achieved 4,6. Just as deviations from the average expectable environment potentiate some individuals toward the development of maladaptation, others demonstrate adaptation in the face of the same challenges 7,8,9. Thus, it is equally important to comprehend the mechanisms that promote adaptation among individuals experiencing significant adversity as it is to investigate the developmental trajectories toward maladaptation. Research conducted on biological, as well as psychological, protective factors is critically important for discovering mechanisms and processes that contribute to the development of either the recovery of function or resilient adaptation in the face of significant adversity 10,11,12. Resilience is conceived as a dynamic developmental process encompassing the attainment of positive adaptation within the context of significant adversity 8,13,14. There are two critical conditions that are implicit within this conceptualization of resilience: a) exposure to significant threat, severe adversity, or trauma; and b) the achievement of positive adaptation despite major assaults on the developmental process 8,14. For four decades, researchers interested in children who develop well in the context of significant adversity have endeavored to enhance understanding of the diverse pathways to psychopathology, to elucidate the processes that eventuate in normal development, and to inform preventive interventions and social policies that could improve the lives of vulnerable children and families 7,15,16,17,18. Investigations in the area of risk and resilience have led scientists to rethink their prior assumptions about the causes and course of psychopathology and have resulted in a reformulation of the deficit etiological models that characterized earlier viewpoints about the development of children who have experienced disadvantage and great adversity 9,19,20. Studies conducted on individuals at high risk for psychopathology and on persons with mental disorders frequently portrayed the developmental course as deterministic, inevitably resulting in maladaptive and pathological outcomes. Investigations focusing on genetic and biological predispositions to psychopathology, assaults on development associated with inadequate caregiving, and traumatic occurrences within the home — such as child maltreatment and domestic violence, exposure to community violence, chronic illness, and catastrophic life events — graphically convey the multiplicity of risks that can eventuate in disordered outcomes. As researchers discovered that not all high-risk children manifested the dire consequences that extant theories of psychopathology predicted, comprehending the processes through which children at risk did not develop psychopathology became viewed as important for informing theories on the development of maladaptation and pathology. Before investigations on resilience could be initiated, a significant and illustrious history of research detailing the precursors to, as well as the contemporary patterns of, stress resistance had to take place (e.g., 8,21). In many of these early studies, researchers had discovered evidence of adaptive behavior; however, the nomenclature for labeling these results as indicative of resilience had not yet emerged. The historical roots of resilience can be traced to early programs of research on individuals with schizophrenia and on persons exposed to parental mental illness, extreme stress and poverty, as well as on the functioning of individuals who experienced traumatic occurrences earlier in their lives 7,15,22,23. Early investigations of severely disordered schizophrenic patients were focused primarily on understanding maladaptive behavior, and the subset of patients who showed relatively adaptive patterns were considered atypical and afforded little attention. By the middle of the 20th century, researchers had discovered that people with schizophrenia with the least severe courses of illness were characterized by a premorbid history of a relative competence at work, good social relations, marriage and the capacity to fulfill responsibility (see 23). In a parallel fashion, studies of children of mothers with schizophrenia played a crucial role in the emergence of childhood resilience as a major theoretical and empirical topic 16,19,24. Additionally, Werner's longitudinal study 17,18, that systematically searched for protective forces that differentiated children with healthy adaptation profiles from those who were comparatively less well adjusted, was a groundbreaking investigation. Evidence that many of these children experiencing great adversity thrived despite their high-risk status led to increasing empirical efforts to understand individual variations in response to adversity. Early empirical efforts were primarily focused on the personal qualities of “resilient children”, such as autonomy or high self-esteem 25. As work in the area evolved, however, researchers increasingly acknowledged that resilience may often derive from factors external to the child 8. Subsequent research led to the delineation of these sets of factors implicated in the development of resilience: a) attributes of the children themselves; b) aspects of their families; and c) characteristics of their wider social environments 8,25. In recent decades, there has been a shift in the focus of empirical investigations; rather than searching for protective factors, researchers are increasingly striving to discover the mechanisms underlying resilient functioning 8. This focus on processes as opposed to identifying factors has enabled scientists to design prevention and intervention strategies that are developmentally sensitive for promoting resilience in persons experiencing significant adversity or trauma 26,27,28. Knowledge of the processes contributing to resilient functioning can enable prevention and intervention scientists to capitalize on periods of developmental change and transitions as unique opportunities for promoting positive adaptation during significant adversity or trauma 27,29. As S. Luthar asserted, “it is far more prudent to promote the development of resilient functioning early in the course of development rather than to implement treatments to repair disorders once they are already crystallized” 7. Randomized control trial (RCT) preventive interventions may be conceptualized as true experiments in altering the course of development 30, thereby presenting opportunities to test existing developmental theories as well as to provide insights into the etiology and course of positive adaptational outcomes in individuals experiencing significant adversity 8,31. As research on resilience has evolved and transformed over the years, it has become clear that the attainment of positive adaptation in the face of significant adversity involves a developmental progression; new vulnerabilities and challenges and/or strengths and opportunities often emerge with changing circumstances over the life course 8. Resilience is not something an individual “has” — it is a multiply determined developmental process that is not fixed or immutable. Hence, it is important to conduct longitudinal studies of the determinants of resilient functioning. In this regard, longitudinal studies on resilience should focus not only on assessing the stability of the construct over developmental time, but also on the ability of formerly resilient individuals to “bounce back” or to recover positive functioning experiencing periods and their prior resilient adaptation resilient adaptation may be achieved at in the life there is a for research on the achievement of positive outcomes at different in development, in and in life 8. the the empirical study of resilience focused on and of, and to, the and did not biological or studies were prior to the of for the and biological of and Evidence from earlier and investigations of resilience on a of attributes of child and environment that to be of adaptation and there were and in the early studies more contemporary investigations to the factors associated with resilient a) with and in the and b) c) positive of to be in the environment (i.e., and and and with and in and a to active and the capacity to and have all been associated with resilient functioning positive stressful occurrences in less and the ability to adverse experiences in a positive and to trauma have each been to resilience the relative of as to developmental on the of adaptive outcomes in the face of adversity was primarily to the of that about the and organization of the There was not about development and function to their role in the and of normal and mental in their to the development of resilient adaptation of is about the course, and consequences of resilient functioning in the face of adversity have been from investigations that focused on relatively of it is from the by developmental psychopathologists that toward a understanding of resilient adaptation the of research and strategies that for the of of within and of the In the a of scientists have researchers to and genetic into their investigations of the developmental pathways to resilient functioning in and have it more to conduct research on the development of resilience from a perspective In the of with many associated an to current and to the study of it is critically important to in that biological not function more the functioning of the of or more systems, through a developmental of influenced processes this increasing of the of many of processes in to the understanding of a such as it is resilience researchers to the of of and within systems and psychological are to in research on resilience and in level and all of the of on is different of as scientists more about of resilience researchers their work at each level to develop theories that are all function in they the risk of theories that be from has either been or is Just as is the in systems it is critical that there be an that all of about complex systems in the development of resilience conditions of child maltreatment a in severe stress that challenges and frequently development diverse of biological and psychological functioning The conditions associated with maltreatment a severe from the average expectable children are to in and development, social and children are to develop a of relatively vulnerability factors, at great risk for maladaptation and not all individuals who have been and to the extreme adversity in their of some individuals despite experiencing significant stress and trauma an to discover processes at of that are to be to in the face of adversity, yet less more stress exposure children develop and function despite experiencing a of for developmental theories of and for prevention and In a longitudinal of the pathways to resilience in to there were different pathways to resilient functioning in and children from and to there were between these in recovery of or in functioning over the of the study children than children on of resilient functioning (e.g., competence with with many of these or of each of the years, children a level of resilient functioning than did the Additionally, the of maladaptive functioning by children the course of this longitudinal study was these the impact that maltreatment experiences on functioning and to the of their In this also on the of resilient functioning in and of these that there was a of children than children in the resilient functioning a of than children competence thereby an of resilient the study that children the ability to some resilience in the of chronic and adversity. The of resilient in of the children is for great as are characteristics of all The of such the of the is and also factors that to the development of resilient functioning in the of and For the the major of resilient functioning were the characteristics of (i.e., the ability to and control and and (i.e., the of relative in and to and positive In for the positive with their and and played in the of adaptive functioning. the high of and in it that factors be more to the attainment of resilience in the characteristics and processes were more important in resilient adaptation in the of and in with (i.e., to well for the development of resilient adaptation in Through a more and of and (i.e., resilient children who function in a resilient may be more to is for adaptation in their adverse home is that their more may from of maltreatment In the more of resilient may not be well for adaptation in such may and from others that could in risk for maltreatment the of this longitudinal of the processes underlying resilience in two The perspective that this research into of and allows for biological and psychological mechanisms within the same This perspective not to level of over and it of between and and and This theoretical perspective a for the of a perspective into In the of and in and children from that the positive and ability associated with resilient functioning be associated with relatively of the and of in has that this a that has the two of the have been to be in the is associated with positive and the is with and in positive and good have been associated with resilient adaptation Thus, the potential of with resilience in their with and central between children with high and resilient such that characterized those children who were on competence (e.g., good relations, to of and a of on of of the to the of resilience in and The of a such as in the context of resilient adaptation that there is that be in the process of resilience over the course of Resilience is a process between time, of which at viewed development, the relative of biological and psychological inevitably may also In conducted in resilient functioning in and children in to the of two and as well as the of and was The to investigate as potential of resilience are the two of of the The capacity of individuals to in response to exposure to trauma is important for an impact a diverse of biological on the and central systems As in the and research on the pathways to resilient adaptation a of resilience that of relations, and of and that and and the associated with stress (i.e., and and to at different of and biological factors each unique to as is often the in child can to characterized by biological systems, through a of causes and that can change the systems, and the balance that and is to the adaptation to stress that the be over and can be conceived as a biological — that the systems that the adapt to and a protective function in the also may take in the development of processes or that of were to of resilient for the may that children are experiencing stress exposure are in their ability to adapt the of in were as a function of the of maltreatment children with high had resilient functioning than children with of The positive role of for children is from the more of to resilient functioning as discovered in the and children in this research on has that children exhibit of may be that the of children who were to to with the life was a striving for resilient adaptation. 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Atypical Antipsychotics: CATIE Study, Drug-Induced Movement Disorder and Resulting Iatrogenic Psychiatric-Like Symptoms, Supersensitivity Rebound Psychosis and Withdrawal Discontinuation Syndromes

Chronic illness can result in chronicity of clinical practice. As we have moved away from prescribing classical antipsychotics and tricyclic antidepressants, issues remain with the use of atypical antipsychotics and second-generation antidepressants that need to be addressed, namely, iatrogenic discontinuation syndromes and supersensitivity psychiatric symptoms. An optimal maintenance drug treatment consists of regular attempts to reduce the dose by finding a minimal therapeutic dose, regularly asking the question of when to reduce or withdraw treatment and for which patients, and moreover, why it is difficult to decrease a given drug treatment. Recently, Falloon [1] proposed that maintenance pharmacotherapy in schizophrenia will depend on finally finding minimally effective doses through ‘extensive training in stress management’. In the long-term treatment of major depression, Fava [2] has hypothesized that antidepressants can aggravate the course of depressive illness. Lambert [3] recently suggested that ‘antipsychotic-switching syndromes’, which include discontinuation syndromes, are a ‘major barrier’ to adjusting antipsychotic treatment. In this paper, we propose that to achieve optimal maintenance treatment with antipsychotics, and to reduce or withdraw antipsychotics effectively, we must distinguish syndromes associated with discontinuing antipsychotics, such as supersensitivity psychosis, from true relapse. While the prevalence and incidence of drug-induced movement disorder(s) (DIMD) has continuously decreased with atypical antipsychotics, DIMD persist as do psychiatric and psychiatric-like symptoms associated with DIMD, and these must also be identified and evaluated. Persistent DIMD have been found to be a predictor of the later emergence of tardive dyskinesia (TD) and supersensitivity psychosis [4]. At present, we need to determine the relative risk of iatrogenic discontinuation syndromes, DIMD and DIMD psychiatric symptoms resulting from atypical antipsychotics. Although atypical antipsychotics are now most commonly prescribed, a debate has emerged on the differences between classical and atypical antipsychotics following the results of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study [5]. The question that comes to the forefront is why recent studies are no longer finding well-established differences between these two generations in terms of efficacy and DIMD. Reasons to explain why recent schizophrenia studies have found reduced drug and placebo differences were examined at the International Society for CNS Clinical Trials and Methodology Annual Mid-Year Conference [6]. While the fact must be considered that patients included in recent studies have less severe illness with symptoms that are better controlled than in past studies (likely due to earlier treatment), the issue that psychiatric symptoms specific to schizophrenia are not being adequately measured nor differentiated from psychiatric and psychiatric-like symptoms associated with DIMD is crucial to answering this question. For example, it is hard to believe that in a recent review of psychomotor slowing in schizophrenia, the authors, when evaluating its effect on measurement and treatment research to improve cognition in schizophrenia (MATRICS), nearly completely ignored the influence of akinesia and DIMD on neuropsychological tests in schizophrenia and the importance of accurate DIMD measurements [7]. As we pursue this ongoing discussion, we recommend the discontinuation of all classical antipsychotics due to their neurotoxic association with a high prevalence of DIMD and increases in basal ganglia volumes [8], and now address how to prescribe atypical antipsychotics most effectively, by taking into account DIMD-associated psychiatric symptoms and iatrogenic discontinuation syndromes. The first widely prescribed atypical antipsychotic, risperidone, was first approved in Canada in 1993 following the publication of the Canadian Multicenter Risperidone Study, which reported clear advantages of risperidone over haloperidol and the placebo, and significantly less appearance of DIMD with risperidone than haloperidol [9]. DIMD includes the 4 types of movement disorders induced by antipsychotics: parkinsonism, dystonia, dyskinesia and akathisia [10]. These findings were confirmed by the American Risperidone Study [11] and several other studies reporting greater efficacy of risperidone over classical antipsychotics in terms of cost-efficiency [12] and the clinical management of patients with schizophrenia [13,14,15,16,17]. However, the CATIE study [5] challenged these results. The CATIE study found that of the 4 atypical antipsychotics studied, olanzapine was the only atypical to be more efficacious than the classical antipsychotic perphenazine, and to be highly superior to risperidone for discontinuation of treatment, due to lack of efficacy [5]. Olanzapine is known to produce less DIMD compared to risperidone, therefore one would expect psychiatric symptoms caused by DIMD to be less frequent with olanzapine than risperidone. The expected higher rate of DIMD-induced emergent psychiatric symptoms associated with risperidone would explain the CATIE results, showing risperidone to be significantly less efficacious than olanzapine [5], despite risperidone being known to be at least as efficacious as olanzapine for true schizophrenic symptoms. Furthermore, the rating scales used to measure DIMD did not find the well-established differences between the 5 antipsychotics for DIMD rates [5]. Thus, we propose that DIMD and DIMD-induced psychiatric symptoms were confounded with true schizophrenic symptoms in the CATIE study. DIMD-associated psychiatric symptoms could be classified into 3 types: (1) emergent psychiatric symptoms caused by DIMD, such as akinesia inducing depression, akathisia inducing anxiety; (2) iatrogenic psychiatric-like symptoms resulting from confounding DIMD with psychiatric symptoms, such as akinesia confounded with psychomotor retardation, akathisia with agitation; (3) supersensitivity psychosis symptoms associated with DIMD. In the CATIE study, quetiapine (mean dose = 543.4 mg/day), which shares a low rate of DIMD with olanzapine, was also found to be significantly less efficacious compared to olanzapine, but in contrast to risperidone, this lack of efficacy could be due to psychiatric symptoms related to supersensitivity psychosis explained by quetiapine’s loose binding properties at the D2 receptor [18]. Patients taking quetiapine had a completion rate of 18% out of 329 patients, whereas in our 3-year prospective study of quetiapine monotherapy with a lower mean dose of 487 mg/day (thus less likely to develop therapeutic tolerance), the completion rate was 21.7% out of 23 patients; 6 of 7 patients who relapsed, after a minimum 3 months of stabilized quetiapine treatment, met the criteria for supersensitivity psychosis [19]. Without distinguishing these DIMD-associated psychiatric symptoms from symptoms due to the original illness, the major impact of atypical antipsychotics is on the reduction of DIMD and TD [10, 20,] and their beneficial effects on psychosis are masked by DIMD emergent psychiatric symptoms, including supersensitivity psychosis. We will review 4 multicenter trials, which include a total of 14,497 patients, to illustrate how psychiatric and schizophrenic symptoms are confounded with DIMD-associated psychiatric symptoms.TD epidemiology has changed significantly since the introduction of atypical antipsychotics, with a constant decline in its prevalence [10]. TD, classified as a DIMD, is a hyperkinetic, involuntary and purposeless movement disorder [10, 20]. Considered as the most significant side effect of classical antipsychotics, TD has been associated with antipsychotics and gastrointestinal neuroleptics, and usually occurs after several years of treatment. Persistent TD can also occur after short-term exposure to classical antipsychotics and gastrointestinal neuroleptics even at low doses and for as few as 2 months [8,21,22,23], while reversible and withdrawal dyskinesias share properties with levodopa-induced dyskinesia [24]. We conducted several epidemiological studies of TD [4,25,26,27] and in 1975, using the National Institute of Mental Health (NIMH) psychopharmacology criteria, we found a 31% prevalence of TD in 261 outpatients with schizophrenia [25]. We also evaluated these patients according to the Schooler and Kane research diagnostic criteria and found a 22% prevalence of TD. This variability of findings related to defining criteria complicates comparisons across studies [10]. In a 5-year follow-up study of 169 of the same patients [4, 25], 45% met the research diagnostic criteria for TD. In 1975, 131 of the 261 patients did not meet the research diagnostic for TD, and in 1980 treatment-emergent TD was found in 46 of the patients who did not have it in 1975, for a 5-year cumulative incidence rate of 35% and a mean annual incidence rate of 8.4%. When corrected for remissions, the mean annual incidence rate decreased to 2.9%. This incidence rate, which includes both patients who developed and remitted from TD over time, is similar to results found by other studies during the same time period [28, 29]. The cumulative incidence of treatment-emergent TD in the study by Kane et al. [29] was 12% after 4 years and 40% after 8 years of neuroleptic exposure, which is similar to our finding of an annual incidence rate (corrected for remissions) of 3% for classical antipsychotics. In a study carried out in 130 lithium-treated affective disorder patients previously, but less, exposed to antipsychotics, we found a TD prevalence of 9.2% [26], which was a quarter of the incidence reported in our previous studies on patients with schizophrenia who had greater exposure to antipsychotics. In this time period of classical antipsychotics, 2 meta-analyses (including mostly patients with schizophrenia) reported mean TD prevalences of 23% [30] and 20% [31]. In view of the fact that 58% of patients treated with classical antipsychotics will develop treatment-emergent TD after 10–15 years of treatment [4], and the known beneficial neuroprotective effects of atypical antipsychotics on TD [32] and on increased basal ganglia volumes induced by classical antipsychotics [8], we recommend the discontinuation of all classical antipsychotics due to their neurotoxic effects. In the time period of both classical and atypical antipsychotics, the following multicenter studies (n = 3,753) evaluated the incidence and prevalence of TD, using the same definitions, Extrapyramidal Symptom Rating Scale [20] and training videotapes as in the previous time period. In the first study, an annual TD incidence of 0.68% was reported prospectively in 725 patients with schizophrenia, treated with the long-acting injectable atypical antipsychotic risperidone [27, 33]. Treatment-emergent TD was found in 12 of 587 patients without dyskinesia at the baseline [33]; however, expert case assessment determined 7 cases (1.19%) of withdrawal dyskinesia (3 cases resolved, 4 cases unchanged), 1 case (0.17%) of reversible dyskinesia and 4 cases (0.68%) of persistent treatment-emergent TD. Of the patients with baseline dyskinesia, 28.4% improved, no longer met TD criteria and maintained this response [33]. This annual treatment-emergent TD incidence of 0.68% with atypical antipsychotics is only 22% of the annual incidence of 3% reported with classical antipsychotics [4]. In the second study, the Schizophrenia International Suicide Prevention Trial (67 centers in 11 countries) [34], 980 patients with schizophrenia, or schizoaffective disorders, taking an atypical alone (25.6%), a classical alone (31.5%) or both a classical and an atypical antipsychotic (42.9%) were included from March 19, 1998, to February 14, 1999, and TD was found at the baseline in 115 (12%) patients [27, 35]. Thus, after 10 years in the time period of both classical and atypical antipsychotics, the overall prevalence of TD decreased by at least twofold compared to our previous 1979–1988 studies with classical antipsychotics [4, 25], using the same definitions, Extrapyramidal Symptom Rating Scale and training videotapes. In the third study (baseline data from three Ris-Consta multicenter studies) [27, 36] carried out 1 year later, 2,048 patients were included from March 21, 1999, to December 15, 2000, and TD was found at the baseline in 209 patients (10.2%), using the same methodology. This study showed a further decrease in the prevalence of TD after an additional year of atypical use. This changing epidemiology of TD with atypical antipsychotics is confirmed by Correll et al. [37] in a systematic review of 1-year prospective studies with atypical antipsychotics, and by Jeste et al. [38] in a 1-year study of elderly patients treated with risperidone. In conclusion, following the introduction of atypical antipsychotics, the prevalence and incidence of TD have significantly decreased. However, the risk for TD still exists with both atypical and classical antipsychotics, and there is a need for continued surveillance of emerging cases of TD in patients taking antipsychotics [39], especially as the current debate continues on the differences in efficacy between these two generations of antipsychotics following results from studies such as the CATIE [5, 39]. Furthermore, Kane [39] has pointed out that newly trained clinicians using mostly atypical antipsychotics may not have had the same exposure to TD as previously trained clinicians.A high prevalence of all 4 types of DIMD (parkinsonism, dystonia, dyskinesia and akathisia) remains. In the Schizophrenia International Suicide Prevention Trial (n = 980), a prevalence of 57.5% of DIMD (n = 551 patients) was found [27, 35]. In the Ris-Consta studies (n = 2,048) [27, 36], 970 patients (47.4%) had DIMD at the baseline, which consisted of 778 patients with parkinsonism (38.0%), 285 patients with akathisia (14%) and 209 patients with TD (10.2%). Thus, nearly 1 patient out of 2 had a definite DIMD in this time period of classical and atypical antipsychotics. In addition, DIMD have been consistently associated with significant psychiatric symptoms as measured by the positive and negative syndrome scale (PANSS) [40, 41]. In the InterSept study (n = 980), which included patients with schizophrenia and schizoaffective disorder who were at risk of suicide, suicidality was associated at baseline with DIMD, parkinsonism, TD and akathisia, and depression was associated with TD and akathisia [27, 35]. Based on these results, we recommend routinely assessing DIMD in patients with schizophrenia with suicidal and depressive symptoms. In the Ris-Consta studies (n = 2,048), baseline DIMD were also significantly associated with the PANSS total score, positive, negative and anxiety/depression symptoms [27, 36]. Greater anxiety and depression were seen in patients with severer DIMD, akathisia and parkinsonism. Higher PANSS negative symptom rating was associated with parkinsonism and higher PANSS total scores were associated with akathisia. In this time period, these last two studies (n = 3,028) show that DIMD persists with atypical antipsychotics, and that patients with DIMD have significantly higher PANSS scores compared to patients without DIMD.These results are in agreement with findings from 2 other multicenter studies: the American CATIE study [5] and the European Schizophrenia Outpatient Health Outcomes (SOHO) study [42]. In the CATIE baseline data, patients with TD (n = 212) were found to have significantly more psychopathology than patients without TD (n = 1,098) as measured by the PANSS total score and PANSS general psychopathology subscale [43]. In the 3-year prospective SOHO study, emergent cases of TD were associated with greater overall psychopathology. An increase in clinical global impression overall symptom severity was longitudinally associated with cases of TD in patients without TD at the baseline (n = The SOHO and the CATIE studies have also examined other for TD. the CATIE and SOHO studies found that other DIMD were associated with TD the CATIE study showed that patients with TD had more parkinsonism akathisia while the SOHO study found that baseline symptoms TD our findings in a prospective study of TD [4]. In to reporting that the incidence of TD was lower in patients taking atypical compared to classical antipsychotics after 6 months the SOHO study showed that the incidence of TD was associated with the incidence of of drug-induced in is crucial to that there is a of DIMD with atypical antipsychotics, which are not and confounded with psychiatric symptoms rating scales used routinely in clinical to DIMD do not DIMD from psychiatric symptoms from the 4 multicenter (n = 14,497 patients) into this the CATIE the [27, the Ris-Consta [27, 36] and the SOHO studies have all confirmed the association of DIMD with psychiatric symptoms. most of the studies included in this measure psychiatric symptoms according to the we propose the following of PANSS psychiatric symptoms associated with emergent psychiatric symptoms caused by DIMD, such as depression and suicidality example, akinesia is known to produce depression, psychomotor and suicidal while akathisia psychomotor and suicidal and TD is also associated with suicidal iatrogenic psychiatric-like symptoms resulting from confounding and DIMD with psychiatric symptoms, such as confounding and with and retardation, akathisia with anxiety and and and dyskinesias with and schizophrenic psychiatric schizophrenic symptoms associated with DIMD caused by supersensitivity psychosis, which we are now to first reported drug-induced associated with TD a in and increased receptor after long-term treatment with classical antipsychotics, and we this supersensitivity psychosis. We that TD and supersensitivity psychosis with the decrease or withdrawal of an antipsychotic, given risk not and at the same The debate continues on how to most withdraw antipsychotic [1] and and psychiatric syndromes associated with types of syndromes have been with the discontinuation of (1) withdrawal syndromes and major (2) syndromes anxiety and which have been reported with and (3) supersensitivity syndromes such as TD and supersensitivity psychosis These discontinuation syndromes all produce psychiatric symptoms that can be confounded with true of the original illness. In a recent review of the on psychosis the importance of between antipsychotic withdrawal effects related to the course of the original illness and drug-induced effects such as supersensitivity psychosis. due to the discontinuation of a drug can be differentiated from the course of original illness and more long-term maintenance treatment could be reduced and in patients The long-term maintenance with second-generation antidepressants and of a major depressive disorder is of the in and during long-term maintenance treatment. The has also recently been to produce a persistent disorder following withdrawal to be related to supersensitivity When discontinuing antipsychotics and antidepressants, the of supersensitivity syndromes and other iatrogenic discontinuation syndromes must be to high doses or of outpatients and with schizophrenia treated with a classical antipsychotic treatment also included 1 but no antidepressants, no and no showed a prevalence of 22% for supersensitivity psychosis The prevalence of TD using Schooler and Kane criteria, was that found for supersensitivity psychosis. cases of supersensitivity psychosis increased the prevalence of supersensitivity psychosis to psychosis was associated with a higher maintenance dose of classical antipsychotics, high and schizophrenia with a The higher antipsychotic dose and higher associated with supersensitivity psychosis to the of supersensitivity and these results that lower doses of antipsychotics could the appearance of supersensitivity psychosis. In this study, there was no found between TD and supersensitivity psychosis, due to TD being associated with schizophrenia and supersensitivity psychosis with higher antipsychotic dose was not to be a risk for TD, whereas increased was associated with TD but not associated with supersensitivity psychosis. is that most patients in this study were treated with which has a high for the D2 which could to both a high incidence of supersensitivity psychosis and DIMD as the drug is known to produce a high incidence of symptoms psychosis, in its masked and withdrawal is known to occur 6 following the decrease or withdrawal of an antipsychotic or 3 months for a long-acting injectable We have proposed that TD and supersensitivity psychosis can result from the of in the caused by following in D2 with high for The of supersensitivity psychosis and TD share can both occur after long-term use of antipsychotics and can and difficult to with of the antipsychotic stress both TD and supersensitivity psychosis and both can be by and by and TD was to be the predictor of supersensitivity psychosis in our and follow-up study of supersensitivity psychosis [4, TD and supersensitivity psychosis may or may not occur in the same time but TD is associated with supersensitivity psychosis when it occurs during withdrawal of antipsychotics These two supersensitivity syndromes have been difficult to study due to the fact that antipsychotics can their appearance further with supersensitivity psychosis is that symptoms the original illness and true however, supersensitivity psychosis can be as it more after of the antipsychotic than true occurs with high doses of antipsychotics and not with antipsychotic treatment and therapeutic to antipsychotic treatment after drug response time, as therapeutic there is further of supersensitivity and further syndromes, TD, can (1) or (2) persistent or (3) reversible or symptoms can persist for several months or years and can still be reversible or When persistent and supersensitivity symptoms symptoms, being severer than the original symptoms, but these supersensitivity symptoms persist in contrast to symptoms and may include symptoms atypical antipsychotics, it has been proposed that supersensitivity psychosis occurs more with antipsychotics with from the D2 receptor The 2 atypical antipsychotics most associated with supersensitivity psychosis are quetiapine and which both have loose binding properties at the D2 receptor An additional which and severe in the withdrawal of is its effect as an receptor Thus, for the withdrawal would be by the receptor following of at this drug in the of the a and psychosis results cases of supersensitivity psychosis have also been reported with olanzapine psychosis was found to be associated with quetiapine in our 3-year study of quetiapine in 23 outpatients with schizophrenia and schizoaffective disorder who had previously been treated with classical antipsychotics risperidone, and had symptoms and of side effects [19]. As in our of the CATIE study, 7 patients after a minimum of 3 months of stabilized treatment and 6 of these patients met the criteria for supersensitivity psychosis [19]. the 11 of patients with baseline TD relapsed, the that TD to supersensitivity psychosis and have been to be efficacious in of patients with supersensitivity psychosis We also recommend the use of in supersensitivity and anxiety disorder induced by the discontinuation of the An can be used in with an antipsychotic or an in to more decrease or withdraw these and find the minimal therapeutic dose for patients who still need long-term treatment. a minimal therapeutic dose with an has an additional for a drug olanzapine, as the dose will significant side In in the of Mental Health psychiatric 35% of patients with a of schizophrenia and For severe cases of schizophrenia, the use of or is in to drug to antipsychotic While is less than or it is superior to for anxiety and the of optimal minimal maintenance drug treatment. proposed the beneficial results of treatment in schizophrenia is their effect We have also related their beneficial effects to an of a We recommend treatment as a first for from treatment, can also be prescribed as with as it has a In a and that and had than other in addition, emerging that may improve DIMD has also been to be effective as an to antipsychotic monotherapy in patients with schizophrenia who treatment We that of cases of schizophrenia can be related to supersensitivity psychosis. In patients for maintenance treatment is a minimal therapeutic dose can be with the use of an that will patients from antipsychotic or conclusion, DIMD-induced psychiatric symptoms and supersensitivity syndromes will to to results such as found in the CATIE study which show that olanzapine is the only atypical antipsychotic more efficacious than a classical The proposed for psychiatric and psychiatric-like symptoms associated with DIMD may to the of all classical antipsychotics and the use of higher doses and longer than of atypical antipsychotics. research is in to develop to distinguish between true and iatrogenic discontinuation syndromes and to to more withdraw antipsychotics and antidepressants by and supersensitivity syndromes, for the antipsychotics and quetiapine and for the may to further of DIMD, TD and supersensitivity psychosis as we to more differences in the of As most of antipsychotics and second-generation antidepressants are not routinely or for more differences in drug will also to prescribe minimal therapeutic doses of antipsychotics and antidepressants for greater efficacy and better in the maintenance has and the last 3 years from and

Psychotherapy and Psychosomatics · editorial or comment · 168 citationsread the source →

Effectiveness of non-pharmaceutical public health interventions against COVID-19: A systematic review and meta-analysis.

Non-Pharmaceutical Public Health Interventions (NPHIs) have been used by different countries to control the spread of the COVID-19. Despite available evidence regarding the effectiveness of NPHSs, there is still no consensus about how policymakers can trust these results. Studies on the effectiveness of NPHSs are single studies conducted in specific communities. Therefore, they cannot individually prove if these interventions have been effective in reducing the spread of the infection and its adverse health outcomes. In this systematic review, we aimed to examine the effects of NPHIs on the COVID-19 case growth rate, death growth rate, Intensive Care Unit (ICU) admission, and reproduction number in countries, where NPHIs have been implemented. We searched relevant electronic databases, including Medline (via PubMed), Scopus, CINAHL, Web of Science, etc. from late December 2019 to February 1, 2021. The key terms were primarily drawn from Medical Subject Heading (MeSh and Emtree), literature review, and opinions of experts. Peer-reviewed quasi-experimental studies were included in the review. The PROSPERO registration number is CRD42020186855. Interventions were NPHIs categorized as lockdown, stay-at-home orders, social distancing, and other interventions (mask-wearing, contact tracing, and school closure). We used PRISMA 2020 guidance for abstracting the data and used Cochrane Effective Practice and Organization of Practice (EPOC) Risk of Bias Tool for quality appraisal of the studies. Hartung-Knapp-Sidik-Jonkman random-effects model was performed. Main outcomes included COVID-19 case growth rate (percentage daily changes), COVID-19 mortality growth rate (percentage daily changes), COVID-19 ICU admission (percentage daily changes), and COVID-19 reproduction number changes. Our search strategies in major databases yielded 12,523 results, which decreased to 7,540 articles after eliminating duplicates. Finally, 35 articles qualified to be included in the systematic review among which 23 studies were included in the meta-analysis. Although studies were from both low-income and high-income countries, the majority of them were from the United States (13 studies) and China (five studies). Results of the meta-analysis showed that adoption of NPHIs has resulted in a 4.68% (95% CI, -6.94 to -2.78) decrease in daily case growth rates, 4.8% (95 CI, -8.34 to -1.40) decrease in daily death growth rates, 1.90 (95% CI, -2.23 to -1.58) decrease in the COVID-19 reproduction number, and 16.5% (95% CI, -19.68 to -13.32) decrease in COVID-19 daily ICU admission. A few studies showed that, early enforcement of lockdown, when the incidence rate is not high, contributed to a shorter duration of lockdown and a lower increase of the case growth rate in the post-lockdown era. The majority of NPHIs had positive effects on restraining the COVID-19 spread. With the problems that remain regarding universal access to vaccines and their effectiveness and considering the drastic impact of the nationwide lockdown and other harsh restrictions on the economy and people's life, such interventions should be mitigated by adopting other NPHIs such as mass mask-wearing, patient/suspected case isolation strategies, and contact tracing. Studies need to address the impact of NPHIs on the population's other health problems than COVID-19.

PloS one · meta-analysis · 86 citationsread the source →

Single-arm trial of the second version of an acceptance & commitment therapy smartphone application for smoking cessation.

Background: The first randomized trial of a smartphone application (app) for adult smoking cessation (SmartQuit 1.0) revealed key features that predict cessation. These findings guided the revision of this Acceptance & Commitment Therapy (ACT)-based application (SmartQuit 2.0), which was primarily tested to examine participant receptivity, short-term cessation and reduction, and the relationship between program completion, smoking cessation and reduction. Secondarily, outcomes were descriptively compared with the SmartQuit1.0 trial. Method: Adult participants (78% female, 25% with high school or less education, 30% unemployed) were recruited into the single-arm pilot trial (N=99) of SmartQuit 2.0 with a two-month follow-up (85% retention). Results: Regarding receptivity, 84% of participants were satisfied with SmartQuit 2.0 (vs. 59% for SmartQuit1.0), 73% would recommend it to a friend (vs. 48% for SmartQuit1.0), 81% found the ACT exercises useful for quitting (vs. 44% for SmartQuit1.0). At the 2-month follow-up, the quit rates were 21% for 7-day point prevalence (vs. 23% for SmartQuit1.0), 11% for 30-day point prevalence (vs. 13% for SmartQuit1.0), and 75% of participants reduced their smoking frequency (vs. 57% for SmartQuit1.0). Among program completers (24% of total sample), the quit rates were 33% for 7-day point prevalence, 28% for 30-day point prevalence, and 88% of participants reduced their smoking frequency. Conclusions: The revised app had high user receptivity, modest quit rates, and high smoking reduction rates. Program completion may be key to boosting the app's effectiveness.

Drug and alcohol dependence · 66 citationsread the source →

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

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

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

Physical activity for women with breast cancer after adjuvant therapy.

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

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

Psychological interventions for parents of children and adolescents with chronic illness.

Background: Psychological therapies for parents of children and adolescents with chronic illness aim to improve parenting behavior and mental health, child functioning (behavior/disability, mental health, and medical symptoms), and family functioning. This is an updated version of the original Cochrane Review (2012) which was first updated in 2015. Objectives: To evaluate the efficacy and adverse events of psychological therapies for parents of children and adolescents with a chronic illness. Search methods: We searched CENTRAL, MEDLINE, Embase, PsycINFO, and trials registries for studies published up to July 2018. Selection criteria: Included studies were randomized controlled trials (RCTs) of psychological interventions for parents of children and adolescents with a chronic illness. In this update we included studies with more than 20 participants per arm. In this update, we included interventions that combined psychological and pharmacological treatments. We included comparison groups that received either non-psychological treatment (e.g. psychoeducation), treatment as usual (e.g. standard medical care without added psychological therapy), or wait-list. Data collection and analysis: We extracted study characteristics and outcomes post-treatment and at first available follow-up. Primary outcomes were parenting behavior and parent mental health. Secondary outcomes were child behavior/disability, child mental health, child medical symptoms, and family functioning. We pooled data using the standardized mean difference (SMD) and a random-effects model, and evaluated outcomes by medical condition and by therapy type. We assessed risk of bias per Cochrane guidance and quality of evidence using GRADE. Main results: We added 21 new studies. We removed 23 studies from the previous update that no longer met our inclusion criteria. There are now 44 RCTs, including 4697 participants post-treatment. Studies included children with asthma (4), cancer (7), chronic pain (13), diabetes (15), inflammatory bowel disease (2), skin diseases (1), and traumatic brain injury (3). Therapy types included cognitive-behavioural therapy (CBT; 21), family therapy (4), motivational interviewing (3), multisystemic therapy (4), and problem-solving therapy (PST; 12). We rated risk of bias as low or unclear for most domains, except selective reporting bias, which we rated high for 19 studies due to incomplete outcome reporting. Evidence quality ranged from very low to moderate. We downgraded evidence due to high heterogeneity, imprecision, and publication bias. Evaluation of parent outcomes by medical conditionPsychological therapies may improve parenting behavior (e.g. maladaptive or solicitous behaviors; lower scores are better) in children with cancer post-treatment and follow-up (SMD -0.28, 95% confidence interval (CI) -0.43 to -0.13; participants = 664; studies = 3; SMD -0.21, 95% CI -0.37 to -0.05; participants = 625; studies = 3; I2 = 0%, respectively, low-quality evidence), chronic pain post-treatment and follow-up (SMD -0.29, 95% CI -0.47 to -0.10; participants = 755; studies = 6; SMD -0.35, 95% CI -0.50 to -0.20; participants = 678; studies = 5, respectively, moderate-quality evidence), diabetes post-treatment (SMD -1.39, 95% CI -2.41 to -0.38; participants = 338; studies = 5, very low-quality evidence), and traumatic brain injury post-treatment (SMD -0.74, 95% CI -1.25 to -0.22; participants = 254; studies = 3, very low-quality evidence). For the remaining analyses data were insufficient to evaluate the effect of treatment. Psychological therapies may improve parent mental health (e.g. depression, anxiety, lower scores are better) in children with cancer post-treatment and follow-up (SMD -0.21, 95% CI -0.35 to -0.08; participants = 836, studies = 6, high-quality evidence; SMD -0.23, 95% CI -0.39 to -0.08; participants = 667; studies = 4, moderate-quality evidence, respectively), and chronic pain post-treatment and follow-up (SMD -0.24, 95% CI -0.42 to -0.06; participants = 490; studies = 3; SMD -0.20, 95% CI -0.38 to -0.02; participants = 482; studies = 3, respectively, low-quality evidence). Parent mental health did not improve in studies of children with diabetes post-treatment (SMD -0.24, 95% CI -0.90 to 0.42; participants = 211; studies = 3, very low-quality evidence). For the remaining analyses, data were insufficient to evaluate the effect of treatment on parent mental health. Evaluation of parent outcomes by psychological therapy typeCBT may improve parenting behavior post-treatment (SMD -0.45, 95% CI -0.68 to -0.21; participants = 1040; studies = 9, low-quality evidence), and follow-up (SMD -0.26, 95% CI -0.42 to -0.11; participants = 743; studies = 6, moderate-quality evidence). We did not find evidence for a beneficial effect for CBT on parent mental health at post-treatment or follow-up (SMD -0.19, 95% CI -0.41 to 0.03; participants = 811; studies = 8; SMD -0.07, 95% CI -0.34 to 0.20; participants = 592; studies = 5; respectively, very low-quality evidence). PST may improve parenting behavior post-treatment and follow-up (SMD -0.39, 95% CI -0.64 to -0.13; participants = 947; studies = 7, low-quality evidence; SMD -0.54, 95% CI -0.94 to -0.14; participants = 852; studies = 6, very low-quality evidence, respectively), and parent mental health post-treatment and follow-up (SMD -0.30, 95% CI -0.45 to -0.15; participants = 891; studies = 6; SMD -0.21, 95% CI -0.35 to -0.07; participants = 800; studies = 5, respectively, moderate-quality evidence). For the remaining analyses, data were insufficient to evaluate the effect of treatment on parent outcomes. Adverse eventsWe could not evaluate treatment safety because most studies (32) did not report on whether adverse events occurred during the study period. In six studies, the authors reported that no adverse events occurred. The remaining six studies reported adverse events and none were attributed to psychological therapy. We rated the quality of evidence for adverse events as moderate. Authors' conclusions: Psychological therapy may improve parenting behavior among parents of children with cancer, chronic pain, diabetes, and traumatic brain injury. We also found beneficial effects of psychological therapy may also improve parent mental health among parents of children with cancer and chronic pain. CBT and PST may improve parenting behavior. PST may also improve parent mental health. However, the quality of evidence is generally low and there are insufficient data to evaluate most outcomes. Our findings could change as new studies are conducted.

The Cochrane database of systematic reviews · meta-analysis · 81 citationsread the source →

From grief, guilt pain and stigma to hope and pride - a systematic review and meta-analysis of mixed-method research of the psychosocial impact of stillbirth.

Background: Despite improvements in maternity healthcare services over the last few decades, more than 2.7 million babies worldwide are stillborn each year. The global health agenda is silent about stillbirth, perhaps, in part, because its wider impact has not been systematically analysed or understood before now across the world. Our study aimed to systematically review, evaluate and summarise the current evidence regarding the psychosocial impact of stillbirth to parents and their families, with the aim of improving guidance in bereavement care worldwide. Methods: Systematic review and meta-summary (quantitative aggregation of qualitative findings) of quantitative, qualitative, and mixed-methods studies. All languages and countries were included. Results: Two thousand, six hundred and nineteen abstracts were identified; 144 studies were included. Frequency effect sizes (FES %) were calculated for each theme, as a measure of their prevalence in the literature. Themes ranged from negative psychological symptoms post bereavement (77 · 1) and in subsequent pregnancies (27 · 1), to disenfranchised grief (31 · 2), and incongruent grief (28 · 5), There was also impact on siblings (23 · 6) and on the wider family (2 · 8). They included mixed-feelings about decisions made when the baby died (12 · 5), avoidance of memories (13 · 2), anxiety over other children (7 · 6), chronic pain and fatigue (6 · 9), and a different approach to the use of healthcare services (6 · 9). Some themes were particularly prominent in studies of fathers; grief suppression (avoidance)(18 · 1), employment difficulties, financial debt (5 · 6), and increased substance use (4 · 2). Others found in studies specific to mothers included altered body image (3 · 5) and impact on quality of life (2 · 1). Counter-intuitively, Some themes had mixed connotations. These included parental pride in the baby (5 · 6), motivation for engagement in healthcare improvement (4 · 2) and changed approaches to life and death, self-esteem, and own identity (25 · 7). In studies from low/middle income countries, stigmatisation (13 · 2) and pressure to prioritise or delay conception (9) were especially prevalent. Conclusion: Experiencing the birth of a stillborn child is a life-changing event. The focus of the consequences may vary with parent gender and country. Stillbirth can have devastating psychological, physical and social costs, with ongoing effects on interpersonal relationships and subsequently born children. However, parents who experience the tragedy of stillbirth can develop resilience and new life-skills and capacities. Future research should focus on developing interventions that may reduce the psychosocial cost of stillbirth.

BMC pregnancy and childbirth · meta-analysis · 201 citationsread the source →

Perceived stress and telomere length: A systematic review, meta-analysis, and methodologic considerations for advancing the field.

Importance: Psychological stress contributes to numerous diseases and may do so in part through damage to telomeres, protective non-coding segments on the ends of chromosomes. Objective: We conducted a systematic review and meta-analysis to determine the association between self-reported, perceived psychological stress (PS) and telomere length (TL). Data sources: We searched 3 databases (PubMed, PsycInfo, and Scopus), completed manual searches of published and unpublished studies, and contacted all study authors to obtain potentially relevant data. Study selection: Two independent reviewers assessed studies for original research measuring (but not necessarily reporting the correlation between) PS and TL in human subjects. 23 studies met inclusion criteria; 22 (totaling 8948 subjects) could be meta-analyzed. Data extraction and synthesis: We assessed study quality using modified MINORS criteria. Since not all included studies reported PS-TL correlations, we obtained them via direct calculation from author-provided data (7 studies), contact with authors (14 studies), or extraction from the published article (1 study). Main outcomes and measures: We conducted random-effects meta-analysis on our primary outcome, the age-adjusted PS-TL correlation. We investigated potential confounders and moderators (sex, life stress exposure, and PS measure validation) via post hoc subset analyses and meta-regression. Results: Increased PS was associated with a very small decrease in TL (n=8724 total; r=-0.06; 95% CI: -0.10, -0.008; p=0.01; α=0.025), adjusting for age. This relationship was similar between sexes and within studies using validated measures of PS, and marginally (nonsignificantly) stronger among samples recruited for stress exposure (r=-0.13; vs. general samples: b=-0.11; 95% CI: -0.27, 0.01; p=0.05; α=0.013). Publication bias may exist; correcting for its effects attenuated the relationship. Conclusions and relevance: Our analysis finds a very small, statistically significant relationship between increased PS (as measured over the past month) and decreased TL that may reflect publication bias, although fully parsing the effects of publication bias from other sample-size correlates is challenging, as discussed. The association may be stronger with known major stressors and is similar in magnitude to that noted between obesity and TL. All included studies used single measures of short-term stress; the literature suggests long-term chronic stress may have a larger cumulative effect. Future research should assess for potential confounders and use longitudinal, multidimensional models of stress.

Brain, behavior, and immunity · meta-analysis · 186 citationsread the source →

Supporting smoking cessation and preventing relapse following a stay in a smoke-free setting: a meta-analysis and investigation of effective behaviour change techniques.

Background and aims: Admission to a smoke-free setting presents a unique opportunity to encourage smokers to quit. However, risk of relapse post-discharge is high, and little is known about effective strategies to support smoking cessation following discharge. We aimed to identify interventions that maintain abstinence following a smoke-free stay and determine their effectiveness, as well as the probable effectiveness of behaviour change techniques (BCTs) used in these interventions. Methods: Systematic review and meta-analyses of studies of adult smokers aged ≥ 18 years who were temporarily or fully abstinent from smoking to comply with institutional smoke-free policies. Institutions included prison, inpatient mental health, substance misuse or acute hospital settings. A Mantel-Haenszel random-effects meta-analysis of randomized controlled trials (RCTs) was conducted using biochemically verified abstinence (7-day point prevalence or continuous abstinence). BCTs were defined as 'promising' in terms of probable effectiveness (if BCT was present in two or more long-term effective interventions) and feasibility (if BCT was also delivered in ≥ 25% of all interventions). Results: Thirty-seven studies (intervention n = 9041, control n = 6195) were included: 23 RCTs (intervention n = 6593, control n = 5801); three non-randomized trials (intervention n = 845, control n = 394) and 11 cohort studies (n = 1603). Meta-analysis of biochemically verified abstinence at longest follow-up (4 weeks-18 months) found an overall effect in favour of intervention [risk ratio (RR) = 1.27, 95% confidence interval (CI) = 1.08-1.49, I2  = 42%]. Nine BCTs (including 'pharmacological support', 'goal-setting (behaviour)' and 'social support') were characterized as 'promising' in terms of probable effectiveness and feasibility. Conclusions: A systematic review and meta-analyses indicate that behavioural and pharmacological support is effective in maintaining smoking abstinence following a stay in a smoke-free institution. Several behaviour change techniques may help to maintain smoking abstinence up to 18 months post-discharge.

Addiction (Abingdon, England) · meta-analysis · 29 citationsread the source →

Probiotics for the prevention of pediatric antibiotic-associated diarrhea.

Background: Antibiotics alter the microbial balance commonly resulting in antibiotic-associated diarrhea (AAD). Probiotics may prevent AAD via providing gut barrier, restoration of the gut microflora, and other potential mechanisms of action. Objectives: The primary objectives were to assess the efficacy and safety of probiotics (any specified strain or dose) used for the prevention of AAD in children. Search methods: MEDLINE, Embase, CENTRAL, CINAHL, and the Web of Science (inception to 28 May 2018) were searched along with registers including the ISRCTN and Clinicaltrials.gov. We also searched the NICE Evidence Services database as well as reference lists from relevant articles. Selection criteria: Randomized, parallel, controlled trials in children (0 to 18 years) receiving antibiotics, that compare probiotics to placebo, active alternative prophylaxis, or no treatment and measure the incidence of diarrhea secondary to antibiotic use were considered for inclusion. Data collection and analysis: Study selection, data extraction, and risk of bias assessment were conducted independently by two authors. Dichotomous data (incidence of AAD, adverse events) were combined using a pooled risk ratio (RR) or risk difference (RD), and continuous data (mean duration of diarrhea) as mean difference (MD), along with corresponding 95% confidence interval (95% CI). We calculated the number needed to treat for an additional beneficial outcome (NNTB) where appropriate. For studies reporting on microbiome characteristics using heterogeneous outcomes, we describe the results narratively. The certainty of the evidence was evaluated using GRADE. Main results: Thirty-three studies (6352 participants) were included. Probiotics assessed included Bacillus spp., Bifidobacterium spp., Clostridium butyricum, Lactobacilli spp., Lactococcus spp., Leuconostoc cremoris, Saccharomyces spp., orStreptococcus spp., alone or in combination. The risk of bias was determined to be high in 20 studies and low in 13 studies. Complete case (patients who did not complete the studies were not included in the analysis) results from 33 trials reporting on the incidence of diarrhea show a precise benefit from probiotics compared to active, placebo or no treatment control. After 5 days to 12 weeks of follow-up, the incidence of AAD in the probiotic group was 8% (259/3232) compared to 19% (598/3120) in the control group (RR 0.45, 95% CI 0.36 to 0.56; I² = 57%, 6352 participants; NNTB 9, 95% CI 7 to 13; moderate certainty evidence). Nineteen studies had loss to follow-up ranging from 1% to 46%. After making assumptions for those lost, the observed benefit was still statistically significant using an extreme plausible intention-to-treat (ITT) analysis, wherein the incidence of AAD in the probiotic group was 12% (436/3551) compared to 19% (664/3468) in the control group (7019 participants; RR 0.61; 95% CI 0.49 to 0.77; P <0.00001; I² = 70%). An a priori available case subgroup analysis exploring heterogeneity indicated that high dose (≥ 5 billion CFUs per day) is more effective than low probiotic dose (< 5 billion CFUs per day), interaction P value = 0.01. For the high dose studies the incidence of AAD in the probiotic group was 8% (162/2029) compared to 23% (462/2009) in the control group (4038 participants; RR 0.37; 95% CI 0.30 to 0.46; P = 0.06; moderate certainty evidence). For the low dose studies the incidence of AAD in the probiotic group was 8% (97/1155) compared to 13% (133/1059) in the control group (2214 participants; RR 0.68; 95% CI 0.46 to 1.01; P = 0.02). Again, assumptions for loss to follow-up using an extreme plausible ITT analysis was statistically significant. For high dose studies the incidence of AAD in the probiotic group was 13% (278/2218) compared to 23% (503/2207) in control group (4425 participants; RR 0.54; 95% CI 0.42 to 0.70; P <0.00001; I² = 68%; moderate certainty evidence).None of the 24 trials (4415 participants) that reported on adverse events reported any serious adverse events attributable to probiotics. Adverse event rates were low. After 5 days to 4 weeks follow-up, 4% (86/2229) of probiotics participants had an adverse event compared to 6% (121/2186) of control participants (RD 0.00; 95% CI -0.01 to 0.01; P < 0.00001; I² = 75%; low certainty evidence). Common adverse events included rash, nausea, gas, flatulence, abdominal bloating, and constipation. After 10 days to 12 weeks of follow-up, eight studies recorded data on our secondary outcome, the mean duration of diarrhea; with probiotics reducing diarrhea duration by almost one day (MD -0.91; 95% CI -1.38 to -0.44; P <0.00001; low certainty evidence). One study reported on microbiome characteristics, reporting no difference in changes with concurrent antibiotic and probiotic use. Authors' conclusions: The overall evidence suggests a moderate protective effect of probiotics for preventing AAD (NNTB 9, 95% CI 7 to 13). Using five criteria to evaluate the credibility of the subgroup analysis on probiotic dose, the results indicate the subgroup effect based on high dose probiotics (≥ 5 billion CFUs per day) was credible. Based on high-dose probiotics, the NNTB to prevent one case of diarrhea is 6 (95% CI 5 to 9). The overall certainty of the evidence for the primary endpoint, incidence of AAD based on high dose probiotics was moderate due to the minor issues with risk of bias and inconsistency related to a diversity of probiotic agents used. Evidence also suggests that probiotics may moderately reduce the duration of diarrhea, a reduction by almost one day. The benefit of high dose probiotics (e.g. Lactobacillus rhamnosus orSaccharomyces boulardii) needs to be confirmed by a large well-designed multi-centered randomized trial. It is premature to draw firm conclusions about the efficacy and safety of 'other' probiotic agents as an adjunct to antibiotics in children. Adverse event rates were low and no serious adverse events were attributable to probiotics. Although no serious adverse events were observed among inpatient and outpatient children, including small studies conducted in the intensive care unit and in the neonatal unit, observational studies not included in this review have reported serious adverse events in severely debilitated or immuno-compromised children with underlying risk factors including central venous catheter use and disorders associated with bacterial/fungal translocation.

The Cochrane database of systematic reviews · meta-analysis · 162 citationsread the source →

Women's and girls' experiences of menstruation in low- and middle-income countries: A systematic review and qualitative metasynthesis.

Background: Attention to women's and girls' menstrual needs is critical for global health and gender equality. The importance of this neglected experience has been elucidated by a growing body of qualitative research, which we systematically reviewed and synthesised. Methods and findings: We undertook systematic searching to identify qualitative studies of women's and girls' experiences of menstruation in low- and middle-income countries (LMICs). Of 6,892 citations screened, 76 studies reported in 87 citations were included. Studies captured the experiences of over 6,000 participants from 35 countries. This included 45 studies from sub-Saharan Africa (with the greatest number of studies from Kenya [n = 7], Uganda [n = 6], and Ethiopia [n = 5]), 21 from South Asia (including India [n = 12] and Nepal [n = 5]), 8 from East Asia and the Pacific, 5 from Latin America and the Caribbean, 5 from the Middle East and North Africa, and 1 study from Europe and Central Asia. Through synthesis, we identified overarching themes and their relationships to develop a directional model of menstrual experience. This model maps distal and proximal antecedents of menstrual experience through to the impacts of this experience on health and well-being. The sociocultural context, including menstrual stigma and gender norms, influenced experiences by limiting knowledge about menstruation, limiting social support, and shaping internalised and externally enforced behavioural expectations. Resource limitations underlay inadequate physical infrastructure to support menstruation, as well as an economic environment restricting access to affordable menstrual materials. Menstrual experience included multiple themes: menstrual practices, perceptions of practices and environments, confidence, shame and distress, and containment of bleeding and odour. These components of experience were interlinked and contributed to negative impacts on women's and girls' lives. Impacts included harms to physical and psychological health as well as education and social engagement. Our review is limited by the available studies. Study quality was varied, with 18 studies rated as high, 35 medium, and 23 low trustworthiness. Sampling and analysis tended to be untrustworthy in lower-quality studies. Studies focused on the experiences of adolescent girls were most strongly represented, and we achieved early saturation for this group. Reflecting the focus of menstrual health research globally, there was an absence of studies focused on adult women and those from certain geographical areas. Conclusions: Through synthesis of extant qualitative studies of menstrual experience, we highlight consistent challenges and developed an integrated model of menstrual experience. This model hypothesises directional pathways that could be tested by future studies and may serve as a framework for program and policy development by highlighting critical antecedents and pathways through which interventions could improve women's and girls' health and well-being. Review protocol registration: The review protocol registration is PROSPERO: CRD42018089581.

PLoS medicine · meta-analysis · 270 citationsread the source →

Interactive telemedicine: effects on professional practice and health care outcomes.

Background: Telemedicine (TM) is the use of telecommunication systems to deliver health care at a distance. It has the potential to improve patient health outcomes, access to health care and reduce healthcare costs. As TM applications continue to evolve it is important to understand the impact TM might have on patients, healthcare professionals and the organisation of care. Objectives: To assess the effectiveness, acceptability and costs of interactive TM as an alternative to, or in addition to, usual care (i.e. face-to-face care, or telephone consultation). Search methods: We searched the Effective Practice and Organisation of Care (EPOC) Group's specialised register, CENTRAL, MEDLINE, EMBASE, five other databases and two trials registers to June 2013, together with reference checking, citation searching, handsearching and contact with study authors to identify additional studies. Selection criteria: We considered randomised controlled trials of interactive TM that involved direct patient-provider interaction and was delivered in addition to, or substituting for, usual care compared with usual care alone, to participants with any clinical condition. We excluded telephone only interventions and wholly automatic self-management TM interventions. Data collection and analysis: For each condition, we pooled outcome data that were sufficiently homogenous using fixed effect meta-analysis. We reported risk ratios (RR) and 95% confidence intervals (CI) for dichotomous outcomes, and mean differences (MD) for continuous outcomes. Main results: We included 93 eligible trials (N = 22,047 participants), which evaluated the effectiveness of interactive TM delivered in addition to (32% of studies), as an alternative to (57% of studies), or partly substituted for usual care (11%) as compared to usual care alone. The included studies recruited patients with the following clinical conditions: cardiovascular disease (36), diabetes (21), respiratory conditions (9), mental health or substance abuse conditions (7), conditions requiring a specialist consultation (6), co morbidities (3), urogenital conditions (3), neurological injuries and conditions (2), gastrointestinal conditions (2), neonatal conditions requiring specialist care (2), solid organ transplantation (1), and cancer (1).Telemedicine provided remote monitoring (55 studies), or real-time video-conferencing (38 studies), which was used either alone or in combination. The main TM function varied depending on clinical condition, but fell typically into one of the following six categories, with some overlap: i) monitoring of a chronic condition to detect early signs of deterioration and prompt treatment and advice, (41); ii) provision of treatment or rehabilitation (12), for example the delivery of cognitive behavioural therapy, or incontinence training; iii) education and advice for self-management (23), for example nurses delivering education to patients with diabetes or providing support to parents of very low birth weight infants or to patients with home parenteral nutrition; iv) specialist consultations for diagnosis and treatment decisions (8), v) real-time assessment of clinical status, for example post-operative assessment after minor operation or follow-up after solid organ transplantation (8) vi), screening, for angina (1).The type of data transmitted by the patient, the frequency of data transfer, (e.g. telephone, e-mail, SMS) and frequency of interactions between patient and healthcare provider varied across studies, as did the type of healthcare provider/s and healthcare system involved in delivering the intervention. We found no difference between groups for all-cause mortality for patients with heart failure (16 studies; N = 5239; RR:0.89, 95% CI 0.76 to 1.03, P = 0.12; I(2) = 44%) (moderate to high certainty of evidence) at a median of six months follow-up. Admissions to hospital (11 studies; N = 4529) ranged from a decrease of 64% to an increase of 60% at median eight months follow-up (moderate certainty of evidence). We found some evidence of improved quality of life (five studies; N = 482; MD:-4.39, 95% CI -7.94 to -0.83; P < 0.02; I(2) = 0%) (moderate certainty of evidence) for those allocated to TM as compared with usual care at a median three months follow-up. In studies recruiting participants with diabetes (16 studies; N = 2768) we found lower glycated haemoglobin (HbA1c %) levels in those allocated to TM than in controls (MD -0.31, 95% CI -0.37 to -0.24; P < 0.00001; I(2)= 42%, P = 0.04) (high certainty of evidence) at a median of nine months follow-up. We found some evidence for a decrease in LDL (four studies, N = 1692; MD -12.45, 95% CI -14.23 to -10.68; P < 0.00001; I(2 =) 0%) (moderate certainty of evidence), and blood pressure (four studies, N = 1770: MD: SBP:-4.33, 95% CI -5.30 to -3.35, P < 0.00001; I(2) = 17%; DBP: -2.75 95% CI -3.28 to -2.22, P < 0.00001; I(2) = 45% (moderate certainty evidence), in TM as compared with usual care. Seven studies that recruited participants with different mental health and substance abuse problems, reported no differences in the effect of therapy delivered over video-conferencing, as compared to face-to-face delivery. Findings from the other studies were inconsistent; there was some evidence that monitoring via TM improved blood pressure control in participants with hypertension, and a few studies reported improved symptom scores for those with a respiratory condition. Studies recruiting participants requiring mental health services and those requiring specialist consultation for a dermatological condition reported no differences between groups. Authors' conclusions: The findings in our review indicate that the use of TM in the management of heart failure appears to lead to similar health outcomes as face-to-face or telephone delivery of care; there is evidence that TM can improve the control of blood glucose in those with diabetes. The cost to a health service, and acceptability by patients and healthcare professionals, is not clear due to limited data reported for these outcomes. The effectiveness of TM may depend on a number of different factors, including those related to the study population e.g. the severity of the condition and the disease trajectory of the participants, the function of the intervention e.g., if it is used for monitoring a chronic condition, or to provide access to diagnostic services, as well as the healthcare provider and healthcare system involved in delivering the intervention.

The Cochrane database of systematic reviews · meta-analysis · 456 citationsread the source →

Interventions for promoting habitual exercise in people living with and beyond cancer.

Background: This is an updated version of the original Cochrane Review published in the Cochrane Library 2013, Issue 9. Despite good evidence for the health benefits of regular exercise for people living with or beyond cancer, understanding how to promote sustainable exercise behaviour change in sedentary cancer survivors, particularly over the long term, is not as well understood. A large majority of people living with or recovering from cancer do not meet current exercise recommendations. Hence, reviewing the evidence on how to promote and sustain exercise behaviour is important for understanding the most effective strategies to ensure benefit in the patient population and identify research gaps. Objectives: To assess the effects of interventions designed to promote exercise behaviour in sedentary people living with and beyond cancer and to address the following secondary questions: Which interventions are most effective in improving aerobic fitness and skeletal muscle strength and endurance? Which interventions are most effective in improving exercise behaviour amongst patients with different cancers? Which interventions are most likely to promote long-term (12 months or longer) exercise behaviour? What frequency of contact with exercise professionals and/or healthcare professionals is associated with increased exercise behaviour? What theoretical basis is most often associated with better behavioural outcomes? What behaviour change techniques (BCTs) are most often associated with increased exercise behaviour? What adverse effects are attributed to different exercise interventions? Search methods: We used standard methodological procedures expected by Cochrane. We updated our 2013 Cochrane systematic review by updating the searches of the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, Embase, AMED, CINAHL, PsycLIT/PsycINFO, SportDiscus and PEDro up to May 2018. We also searched the grey literature, trial registries, wrote to leading experts in the field and searched reference lists of included studies and other related recent systematic reviews. Selection criteria: We included only randomised controlled trials (RCTs) that compared an exercise intervention with usual care or 'waiting list' control in sedentary people over the age of 18 with a homogenous primary cancer diagnosis. Data collection and analysis: In the update, review authors independently screened all titles and abstracts to identify studies that might meet the inclusion criteria, or that could not be safely excluded without assessment of the full text (e.g. when no abstract is available). We extracted data from all eligible papers with at least two members of the author team working independently (RT, LS and RG). We coded BCTs according to the CALO-RE taxonomy. Risk of bias was assessed using the Cochrane's tool for assessing risk of bias. When possible, and if appropriate, we performed a fixed-effect meta-analysis of study outcomes. If statistical heterogeneity was noted, a meta-analysis was performed using a random-effects model. For continuous outcomes (e.g. cardiorespiratory fitness), we extracted the final value, the standard deviation (SD) of the outcome of interest and the number of participants assessed at follow-up in each treatment arm, to estimate the standardised mean difference (SMD) between treatment arms. SMD was used, as investigators used heterogeneous methods to assess individual outcomes. If a meta-analysis was not possible or was not appropriate, we narratively synthesised studies. The quality of the evidence was assessed using the GRADE approach with the GRADE profiler. Main results: We included 23 studies in this review, involving a total of 1372 participants (an addition of 10 studies, 724 participants from the original review); 227 full texts were screened in the update and 377 full texts were screened in the original review leaving 35 publications from a total of 23 unique studies included in the review. We planned to include all cancers, but only studies involving breast, prostate, colorectal and lung cancer met the inclusion criteria. Thirteen studies incorporated a target level of exercise that could meet current recommendations for moderate-intensity aerobic exercise (i.e.150 minutes per week); or resistance exercise (i.e. strength training exercises at least two days per week).Adherence to exercise interventions, which is crucial for understanding treatment dose, is still reported inconsistently. Eight studies reported intervention adherence of 75% or greater to an exercise prescription that met current guidelines. These studies all included a component of supervision: in our analysis of BCTs we designated these studies as 'Tier 1 trials'. Six studies reported intervention adherence of 75% or greater to an aerobic exercise goal that was less than the current guideline recommendations: in our analysis of BCTs we designated these studies as 'Tier 2 trials.' A hierarchy of BCTs was developed for Tier 1 and Tier 2 trials, with programme goal setting, setting of graded tasks and instruction of how to perform behaviour being amongst the most frequent BCTs. Despite the uncertainty surrounding adherence in some of the included studies, interventions resulted in improvements in aerobic exercise tolerance at eight to 12 weeks (SMD 0.54, 95% CI 0.37 to 0.70; 604 participants, 10 studies; low-quality evidence) versus usual care. At six months, aerobic exercise tolerance was also improved (SMD 0.56, 95% CI 0.39 to 0.72; 591 participants; 7 studies; low-quality evidence). Authors' conclusions: Since the last version of this review, none of the new relevant studies have provided additional information to change the conclusions. We have found some improved understanding of how to encourage previously inactive cancer survivors to achieve international physical activity guidelines. Goal setting, setting of graded tasks and instruction of how to perform behaviour, feature in interventions that meet recommendations targets and report adherence of 75% or more. However, long-term follow-up data are still limited, and the majority of studies are in white women with breast cancer. There are still a considerable number of published studies with numerous and varied issues related to high risk of bias and poor reporting standards. Additionally, the meta-analyses were often graded as consisting of low- to very low-certainty evidence. A very small number of serious adverse effects were reported amongst the studies, providing reassurance exercise is safe for this population.

The Cochrane database of systematic reviews · meta-analysis · 153 citationsread the source →

Childhood obesity and adult cardiovascular disease risk factors: a systematic review with meta-analysis.

Background: Overweight and obesity is a major public health concern that includes associations with the development of cardiovascular disease (CVD) risk factors during childhood and adolescence as well as premature mortality in adults. Despite the high prevalence of childhood and adolescent obesity as well as adult CVD, individual studies as well as previous systematic reviews examining the relationship between childhood obesity and adult CVD have yielded conflicting results. The purpose of this study was to use the aggregate data meta-analytic approach to address this gap. Methods: Studies were included if they met the following criteria: (1) longitudinal and cohort studies (including case-cohort), (2) childhood exposure and adult outcomes collected on the same individual over time, (3) childhood obesity, as defined by the original study authors, (4) English-language articles, (5) studies published up to June, 2015, (6) one or more of the following CVD risk factors [systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), non-high-density lipoprotein cholesterol (non-HDL), and triglycerides (TG)], (7) outcome(s) not self-reported, and (8) exposure measurements (child's adiposity) assessed by health professionals, trained investigators, or self-reported. Studies were retrieved by searching three electronic databases as well as citation tracking. Fisher's r to z score was calculated for each study for each outcome. Pooled effect sizes were calculated using random-effects models while risk of bias was assessed using the STROBE instrument. In order to try and identify sources of heterogeneity, random-effects meta-regression was also performed. Results: Of the 4840 citations reviewed, a total of 23 studies were included in the systematic review and 21 in the meta-analysis. The findings suggested that childhood obesity is significantly and positively associated with adult SBP (Zr = 0.11; 95% CI: 0.07, 0.14), DBP (Zr = 0.11; 95% CI: 0.07, 0.14), and TG (Zr =0.08; 95% CI: 0.03, 0.13), and significantly and inversely associated with adult HDL (Zr = -0.06; 95% CI: -0.10, -0.02). For those studies that adjusted for adult body mass index (BMI), associations were reversed, suggesting that adult BMI may be a potential mediator. Nine studies had more than 33% of items that placed them at an increased risk for bias. Conclusions: The results of this study suggest that childhood obesity may be a risk factor for selected adult CVD risk factors. However, a need exists for additional, higher-quality studies that include, but are not limited to, both unadjusted and adjusted measures such as BMI before any definitive conclusions can be reached. Systematic review and meta-analysis: PROSPERO 2015: CRD42015019763 .

BMC public health · meta-analysis · 342 citationsread the source →

Interventions to prevent obesity in children aged 5 to 11 years old.

Background: Prevention of obesity in children is an international public health priority given the prevalence of the condition (and its significant impact on health, development and well-being). Interventions that aim to prevent obesity involve behavioural change strategies that promote healthy eating or 'activity' levels (physical activity, sedentary behaviour and/or sleep) or both, and work by reducing energy intake and/or increasing energy expenditure, respectively. There is uncertainty over which approaches are more effective and numerous new studies have been published over the last five years, since the previous version of this Cochrane review. Objectives: To assess the effects of interventions that aim to prevent obesity in children by modifying dietary intake or 'activity' levels, or a combination of both, on changes in BMI, zBMI score and serious adverse events. Search methods: We used standard, extensive Cochrane search methods. The latest search date was February 2023. Selection criteria: Randomised controlled trials in children (mean age 5 years and above but less than 12 years), comparing diet or 'activity' interventions (or both) to prevent obesity with no intervention, usual care, or with another eligible intervention, in any setting. Studies had to measure outcomes at a minimum of 12 weeks post baseline. We excluded interventions designed primarily to improve sporting performance. Data collection and analysis: We used standard Cochrane methods. Our outcomes were body mass index (BMI), zBMI score and serious adverse events, assessed at short- (12 weeks to < 9 months from baseline), medium- (9 months to < 15 months) and long-term (≥ 15 months) follow-up. We used GRADE to assess the certainty of the evidence for each outcome. Main results: This review includes 172 studies (189,707 participants); 149 studies (160,267 participants) were included in meta-analyses. One hundred forty-six studies were based in high-income countries. The main setting for intervention delivery was schools (111 studies), followed by the community (15 studies), the home (eight studies) and a clinical setting (seven studies); one intervention was conducted by telehealth and 31 studies were conducted in more than one setting. Eighty-six interventions were implemented for less than nine months; the shortest was conducted over one visit and the longest over four years. Non-industry funding was declared by 132 studies; 24 studies were funded in part or wholly by industry. Dietary interventions versus control Dietary interventions, compared with control, may have little to no effect on BMI at short-term follow-up (mean difference (MD) 0, 95% confidence interval (CI) -0.10 to 0.10; 5 studies, 2107 participants; low-certainty evidence) and at medium-term follow-up (MD -0.01, 95% CI -0.15 to 0.12; 9 studies, 6815 participants; low-certainty evidence) or zBMI at long-term follow-up (MD -0.05, 95% CI -0.10 to 0.01; 7 studies, 5285 participants; low-certainty evidence). Dietary interventions, compared with control, probably have little to no effect on BMI at long-term follow-up (MD -0.17, 95% CI -0.48 to 0.13; 2 studies, 945 participants; moderate-certainty evidence) and zBMI at short- or medium-term follow-up (MD -0.06, 95% CI -0.13 to 0.01; 8 studies, 3695 participants; MD -0.04, 95% CI -0.10 to 0.02; 9 studies, 7048 participants; moderate-certainty evidence). Five studies (1913 participants; very low-certainty evidence) reported data on serious adverse events: one reported serious adverse events (e.g. allergy, behavioural problems and abdominal discomfort) that may have occurred as a result of the intervention; four reported no effect. Activity interventions versus control Activity interventions, compared with control, may have little to no effect on BMI and zBMI at short-term or long-term follow-up (BMI short-term: MD -0.02, 95% CI -0.17 to 0.13; 14 studies, 4069 participants; zBMI short-term: MD -0.02, 95% CI -0.07 to 0.02; 6 studies, 3580 participants; low-certainty evidence; BMI long-term: MD -0.07, 95% CI -0.24 to 0.10; 8 studies, 8302 participants; zBMI long-term: MD -0.02, 95% CI -0.09 to 0.04; 6 studies, 6940 participants; low-certainty evidence). Activity interventions likely result in a slight reduction of BMI and zBMI at medium-term follow-up (BMI: MD -0.11, 95% CI -0.18 to -0.05; 16 studies, 21,286 participants; zBMI: MD -0.05, 95% CI -0.09 to -0.02; 13 studies, 20,600 participants; moderate-certainty evidence). Eleven studies (21,278 participants; low-certainty evidence) reported data on serious adverse events; one study reported two minor ankle sprains and one study reported the incident rate of adverse events (e.g. musculoskeletal injuries) that may have occurred as a result of the intervention; nine studies reported no effect. Dietary and activity interventions versus control Dietary and activity interventions, compared with control, may result in a slight reduction in BMI and zBMI at short-term follow-up (BMI: MD -0.11, 95% CI -0.21 to -0.01; 27 studies, 16,066 participants; zBMI: MD -0.03, 95% CI -0.06 to 0.00; 26 studies, 12,784 participants; low-certainty evidence) and likely result in a reduction of BMI and zBMI at medium-term follow-up (BMI: MD -0.11, 95% CI -0.21 to 0.00; 21 studies, 17,547 participants; zBMI: MD -0.05, 95% CI -0.07 to -0.02; 24 studies, 20,998 participants; moderate-certainty evidence). Dietary and activity interventions compared with control may result in little to no difference in BMI and zBMI at long-term follow-up (BMI: MD 0.03, 95% CI -0.11 to 0.16; 16 studies, 22,098 participants; zBMI: MD -0.02, 95% CI -0.06 to 0.01; 22 studies, 23,594 participants; low-certainty evidence). Nineteen studies (27,882 participants; low-certainty evidence) reported data on serious adverse events: four studies reported occurrence of serious adverse events (e.g. injuries, low levels of extreme dieting behaviour); 15 studies reported no effect. Heterogeneity was apparent in the results for all outcomes at the three follow-up times, which could not be explained by the main setting of the interventions (school, home, school and home, other), country income status (high-income versus non-high-income), participants' socioeconomic status (low versus mixed) and duration of the intervention. Most studies excluded children with a mental or physical disability. Authors' conclusions: The body of evidence in this review demonstrates that a range of school-based 'activity' interventions, alone or in combination with dietary interventions, may have a modest beneficial effect on obesity in childhood at short- and medium-term, but not at long-term follow-up. Dietary interventions alone may result in little to no difference. Limited evidence of low quality was identified on the effect of dietary and/or activity interventions on severe adverse events and health inequalities; exploratory analyses of these data suggest no meaningful impact. We identified a dearth of evidence for home and community-based settings (e.g. delivered through local youth groups), for children living with disabilities and indicators of health inequities.

The Cochrane database of systematic reviews · meta-analysis · 40 citationsread the source →

Annual Research Review: Prevention of psychosis in adolescents - systematic review and meta-analysis of advances in detection, prognosis and intervention.

Background: The clinical high-risk state for psychosis (CHR-P) paradigm has facilitated the implementation of psychosis prevention into clinical practice; however, advancements in adolescent CHR-P populations are less established. Methods: We performed a PRISMA/MOOSE-compliant systematic review of the Web of Science database, from inception until 7 October 2019, to identify original studies conducted in CHR-P children and adolescents (mean age <18 years). Findings were systematically appraised around core themes: detection, prognosis and intervention. We performed meta-analyses (employing Q statistics and I 2 test) regarding the proportion of CHR-P subgroups, the prevalence of baseline comorbid mental disorders, the risk of psychosis onset and the type of interventions received at baseline. Quality assessment and publication bias were also analysed. Results: Eighty-seven articles were included (n = 4,667 CHR-P individuals). Quality of studies ranged from 3.5 to 8 (median 5.5) on a modified Newcastle-Ottawa scale. Detection: Individuals were aged 15.6 ± 1.2 years (51.5% males), mostly (83%) presenting with attenuated positive psychotic symptoms. CHR-P psychometric accuracy improved when caregivers served as additional informants. Comorbid mood (46.4%) and anxiety (31.4%) disorders were highly prevalent. Functioning and cognition were impaired. Neurobiological studies were inconclusive. Prognosis: Risk for psychosis was 10.4% (95%CI: 5.8%-18.1%) at 6 months, 20% (95%CI: 15%-26%) at 12 months, 23% (95%CI: 18%-29%) at 24 months and 23.3% (95%CI: 17.3%-30.7%) at ≥36 months. Interventions: There was not enough evidence to recommend one specific treatment (including cognitive behavioural therapy) over the others (including control conditions) to prevent the transition to psychosis in this population. Randomised controlled trials suggested that family interventions, cognitive remediation and fish oil supplementation may improve cognition, symptoms and functioning. At baseline, 30% of CHR-P adolescents were prescribed antipsychotics and 60% received psychotherapy. Conclusions: It is possible to detect and formulate a group-level prognosis in adolescents at risk for psychosis. Future interventional research is required.

Journal of child psychology and psychiatry, and allied disciplines · meta-analysis · 129 citationsread the source →

Interventions to improve return to work in depressed people.

Background: Work disability such as sickness absence is common in people with depression. Objectives: To evaluate the effectiveness of interventions aimed at reducing work disability in employees with depressive disorders. Search methods: We searched CENTRAL (The Cochrane Library), MEDLINE, Embase, CINAHL, and PsycINFO until April 4th 2020. Selection criteria: We included randomised controlled trials (RCTs) and cluster-RCTs of work-directed and clinical interventions for depressed people that included days of sickness absence or being off work as an outcome. We also analysed the effects on depression and work functioning. Data collection and analysis: Two review authors independently extracted the data and rated the certainty of the evidence using GRADE. We used standardised mean differences (SMDs) or risk ratios (RR) with 95% confidence intervals (CI) to pool study results in studies we judged to be sufficiently similar.  MAIN RESULTS: In this update, we added 23 new studies. In total, we included 45 studies with 88 study arms, involving 12,109 participants with either a major depressive disorder or a high level of depressive symptoms. Risk of bias The most common types of bias risk were detection bias (27 studies) and attrition bias (22 studies), both for the outcome of sickness absence. Work-directed interventions Work-directed interventions combined with clinical interventions A combination of a work-directed intervention and a clinical intervention probably reduces days of sickness absence within the first year of follow-up (SMD -0.25, 95% CI -0.38 to -0.12; 9 studies; moderate-certainty evidence). This translates back to 0.5 fewer (95% CI -0.7 to -0.2) sick leave days in the past two weeks or 25 fewer days during one year (95% CI -37.5 to -11.8). The intervention does not lead to fewer persons being off work beyond one year follow-up (RR 0.96, 95% CI 0.85 to 1.09; 2 studies, high-certainty evidence). The intervention may reduce depressive symptoms (SMD -0.25, 95% CI -0.49 to -0.01; 8 studies, low-certainty evidence) and probably has a small effect on work functioning (SMD -0.19, 95% CI -0.42 to 0.06; 5 studies, moderate-certainty evidence) within the first year of follow-up.  Stand alone work-directed interventions A specific work-directed intervention alone may increase the number of sickness absence days compared with work-directed care as usual (SMD 0.39, 95% CI 0.04 to 0.74; 2 studies, low-certainty evidence) but probably does not lead to more people being off work within the first year of follow-up (RR 0.93, 95% CI 0.77 to 1.11; 1 study, moderate-certainty evidence) or beyond (RR 1.00, 95% CI 0.82 to 1.22; 2 studies, moderate-certainty evidence). There is probably no effect on depressive symptoms (SMD -0.10, 95% -0.30 CI to 0.10; 4 studies, moderate-certainty evidence) within the first year of follow-up and there may be no effect on depressive symptoms beyond that time (SMD 0.18, 95% CI -0.13 to 0.49; 1 study, low-certainty evidence). The intervention may also not lead to better work functioning (SMD -0.32, 95% CI -0.90 to 0.26; 1 study, low-certainty evidence) within the first year of follow-up.   Psychological interventions A psychological intervention, either face-to-face, or an E-mental health intervention, with or without professional guidance, may reduce the number of sickness absence days, compared with care as usual (SMD -0.15, 95% CI -0.28 to -0.03; 9 studies, low-certainty evidence). It may also reduce depressive symptoms (SMD -0.30, 95% CI -0.45 to -0.15, 8 studies, low-certainty evidence). We are uncertain whether these psychological interventions improve work ability (SMD -0.15 95% CI -0.46 to 0.57; 1 study; very low-certainty evidence). Psychological intervention combined with antidepressant medication Two studies compared the effect of a psychological intervention combined with antidepressants to antidepressants alone. One study combined psychodynamic therapy with tricyclic antidepressant (TCA) medication and another combined telephone-administered cognitive behavioural therapy (CBT) with a selective serotonin reuptake inhibitor (SSRI). We are uncertain if this intervention reduces the number of sickness absence days (SMD -0.38, 95% CI -0.99 to 0.24; 2 studies, very low-certainty evidence) but found that there may be no effect on depressive symptoms (SMD -0.19, 95% CI -0.50 to 0.12; 2 studies, low-certainty evidence). Antidepressant medication only Three studies compared the effectiveness of SSRI to selective norepinephrine reuptake inhibitor (SNRI) medication on reducing sickness absence and yielded highly inconsistent results. Improved care Overall, interventions to improve care did not lead to fewer days of sickness absence, compared to care as usual (SMD -0.05, 95% CI -0.16 to 0.06; 7 studies, moderate-certainty evidence). However, in studies with a low risk of bias, the intervention probably leads to fewer days of sickness absence in the first year of follow-up (SMD -0.20, 95% CI -0.35 to -0.05; 2 studies; moderate-certainty evidence). Improved care probably leads to fewer depressive symptoms (SMD -0.21, 95% CI -0.35 to -0.07; 7 studies, moderate-certainty evidence) but may possibly lead to a decrease in work-functioning (SMD 0.5, 95% CI 0.34 to 0.66; 1 study; moderate-certainty evidence). Exercise Supervised strength exercise may reduce sickness absence, compared to relaxation (SMD -1.11; 95% CI -1.68 to -0.54; one study, low-certainty evidence). However, aerobic exercise probably is not more effective than relaxation or stretching (SMD -0.06; 95% CI -0.36 to 0.24; 2 studies, moderate-certainty evidence). Both studies found no differences between the two conditions in depressive symptoms. Authors' conclusions: A combination of a work-directed intervention and a clinical intervention probably reduces the number of sickness absence days, but at the end of one year or longer follow-up, this does not lead to more people in the intervention group being at work. The intervention may also reduce depressive symptoms and probably increases work functioning more than care as usual. Specific work-directed interventions may not be more effective than usual work-directed care alone. Psychological interventions may reduce the number of sickness absence days, compared with care as usual. Interventions to improve clinical care probably lead to lower sickness absence and lower levels of depression, compared with care as usual. There was no evidence of a difference in effect on sickness absence of one antidepressant medication compared to another. Further research is needed to assess which combination of work-directed and clinical interventions works best.

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

The ENCOURAGE mortality risk score and analysis of long-term outcomes after VA-ECMO for acute myocardial infarction with cardiogenic shock.

Purpose: This study was designed to identify factors associated with in-intensive care unit (ICU) death and develop a practical mortality risk score for venoarterial-extracorporeal membrane oxygenation (VA-ECMO)-treated acute myocardial infarction (AMI) patients. Long-term survivors' health-related quality of life (HRQOL), anxiety, depression, and post-traumatic stress disorder (PTSD) frequencies were also assessed. Methods: Data from 138 ECMO-treated AMI patients admitted to two French ICUs (2008-2013) were analyzed. ICU survivors contacted >6 months post-ICU discharge were assessed for HRQOL, psychological and PTSD status. Results: Sixty-five patients (47%) survived to ICU discharge. On the basis of multivariable logistic regression analyses, the ENCOURAGE score was constructed with seven pre-ECMO parameters: age >60, female sex, body mass index >25 kg/m(2), Glasgow coma score <6, creatinine >150 μmol/L, lactate (<2, 2-8, or >8 mmol/L), and prothrombin activity <50%. Six months after ECMO, probabilities of survival were 80, 58, 25, 20, and 7% for ENCOURAGE score classes 0-12, 13-18, 19-22, 23-27, and ≥28, respectively. The ENCOURAGE score ROC AUC [0.84 (95% CI 0.77-0.91)] was significantly better than those of the SAVE, SAPS II, and SOFA scores. Survivors' HRQOL evaluated after median follow-up of 32 months revealed satisfactory mental health but persistent physical and emotional-related difficulties, with 34% (95% CI 20-49%) anxiety, 20% (95% CI 8-32%) depression, and 5% (95% CI 0-12%) PTSD symptoms reported. Conclusions: The ENCOURAGE score might be a useful tool to predict mortality of severe cardiogenic shock AMI patients who received VA-ECMO. However, it now needs prospective validation on other populations of AMI patients.

Intensive care medicine · cohort or longitudinal · 351 citationsread the source →

Comparative effectiveness of cognitive behavioural therapy, modafinil, and their combination for treating fatigue in multiple sclerosis (COMBO-MS): a randomised, statistician-blinded, parallel-arm trial.

Background: Fatigue is one of the most disabling symptoms reported by people with multiple sclerosis. Although behavioural and pharmacological interventions might be partly beneficial, their combined effects have not been evaluated for multiple sclerosis fatigue, or examined with sufficient consideration of characteristics that might affect treatment response. In this comparative effectiveness research trial, we compared the effectiveness of cognitive behavioural therapy (CBT), modafinil, and their combination for treating multiple sclerosis fatigue. Methods: This randomised, analyst-blinded, parallel-arm, comparative effectiveness trial was done at two universities in the USA. Adults (aged ≥18 years) with multiple sclerosis and problematic fatigue (Fatigue Severity Scale [FSS] score ≥4) were randomly assigned (1:1:1), using a web-based treatment assignment system with minimisation, to receive CBT, modafinil, or both for 12 weeks. Statisticians were masked to group assignment, but participants, study neurologists, CBT interventionalists, and coordinators were not masked to treatment assignment. The primary outcome was the change in Modified Fatigue Impact Scale (MFIS) from baseline to 12 weeks, assessed using multiple linear regression, adjusted for age, sex, study site, anxiety, pain, baselines MFIS score, and physical activity. Analyses were done by intent to treat. The trial was registered with clinicaltrials.gov, NCT03621761, and is completed. Findings: Between Nov 15, 2018, and June 2, 2021, 336 participants were randomly assigned treatment (114 assigned to CBT, 114 assigned to modafinil, and 108 assigned to combination therapy). At 12 weeks, CBT (n=103), modafinil (n=107), and combination therapy (n=102) were associated with clinically meaningful within-group MFIS reductions of 15·20 (SD 11·90), 16·90 (15·90), and 17·30 (16·20) points, respectively. Change in MFIS scores from baseline to 12 weeks did not differ between groups: relative to combination therapy, the adjusted total mean difference in MFIS change score was 1·88 (95% CI -2·21 to 5·96) for CBT and 1·20 (-2·83 to 5·23) for modafinil. Most common adverse events for modafinil-containing treatment groups included insomnia (eight [7%] for modafinil and eight [7%] for combination therapy) and anxiety (three [3%] for modafinil and nine [8%] for combination therapy). Interpretation: Modafinil, CBT, and combination therapy were associated with similar reductions in the effects of multiple sclerosis fatigue at 12 weeks. Combination therapy was not associated with augmented improvement compared with the individual interventions. Further research is needed to determine whether effects of these interventions on multiple sclerosis-related fatigue is influenced by sleep hygiene and sleepiness. No serious adverse events related to the study drug were encountered. Funding: Patient-Centered Outcomes Research Institute and National Multiple Sclerosis Society.

The Lancet. Neurology · randomised controlled trial · 6 citationsread the source →

Non-pharmacological interventions for reducing aggression and violence in serious mental illness: A systematic review and narrative synthesis.

Background: For people with mental illness that are violent, a range of interventions have been adopted with the aim of reducing violence outcomes. Many of these interventions have been borrowed from other (offender) populations and their evidence base in a Serious Mental Illness (SMI) population is uncertain. Aims: To aggregate the evidence base for non-pharmacological interventions in reducing violence amongst adults with SMI and PD (Personality Disorder), and to assess the efficacy of these interventions. We chose to focus on distinct interventions rather than on holistic service models where any element responsible for therapeutic change would be difficult to isolate. Methods: We performed a systematic review and narrative synthesis of non-pharmacological interventions intended to reduce violence in a SMI population and in patients with a primary diagnosis of PD. Five online databases were searched alongside a manual search of seven relevant journals, and expert opinion was sourced. Eligibility of all returned articles was independently assessed by two authors, and quality of studies was appraised via the Cochrane Collaboration Tool for Assessing Risk of Bias. Results: We included 23 studies of diverse psychological and practical interventions, with a range of experimental and quasi-experimental study designs that included 7 Randomised Controlled Trials (RCTs). The majority were studies of Mentally Disordered Offenders. The stronger evidence existed for patients with a SMI diagnosis receiving Cognitive Behavioural Therapy or modified Reasoning & Rehabilitation (R&R). For patients with a primary diagnosis of PD, a modified version of R&R appeared tolerable and Enhanced Thinking Skills showed some promise in improving attitudes over the short-term, but studies of Dialectical Behaviour Therapy in this population were compromised by high risk of experimental bias. Little evidence could be found for non-pharmacological, non-psychological interventions. Conclusions: The evidence for non-pharmacological interventions for reducing violence in this population is not conclusive. Long-term outcomes are lacking and good quality RCTs are required to develop a stronger evidence base.

European psychiatry : the journal of the Association of European Psychiatrists · systematic review · 29 citationsread the source →

Exploring female genital cutting among west African immigrants.

Although many African women immigrate to the United States from countries with high prevalence rates for female genital cutting (FGC), there has been limited research exploring the incidence and impact of FGC among this growing immigrant population. This pilot study sought to examine the experiences of FGC among West African immigrant women in the US. Of the 23 participants, 7 reported a history of FGC, with Muslim participants reporting significantly higher rates of FGC than Christians (Fisher's Exact = .045). Most of the women who had experienced FGC were from Sierra Leone (Fisher's Exact = .027). Limitations of the study are discussed along with suggestions for future research aimed at understanding the impact of FGC, reducing the prevalence and demand for FGC among African immigrant women and improving the health and quality of life of women who have undergone the procedure.

Journal of immigrant and minority health · 16 citationsread the source →

Successful behavior change in obesity interventions in adults: a systematic review of self-regulation mediators.

Background: Relapse is high in lifestyle obesity interventions involving behavior and weight change. Identifying mediators of successful outcomes in these interventions is critical to improve effectiveness and to guide approaches to obesity treatment, including resource allocation. This article reviews the most consistent self-regulation mediators of medium- and long-term weight control, physical activity, and dietary intake in clinical and community behavior change interventions targeting overweight/obese adults. Methods: A comprehensive search of peer-reviewed articles, published since 2000, was conducted on electronic databases (for example, MEDLINE) and journal reference lists. Experimental studies were eligible if they reported intervention effects on hypothesized mediators (self-regulatory and psychological mechanisms) and the association between these and the outcomes of interest (weight change, physical activity, and dietary intake). Quality and content of selected studies were analyzed and findings summarized. Studies with formal mediation analyses were reported separately. Results: Thirty-five studies were included testing 42 putative mediators. Ten studies used formal mediation analyses. Twenty-eight studies were randomized controlled trials, mainly aiming at weight loss or maintenance (n = 21). Targeted participants were obese (n = 26) or overweight individuals, aged between 25 to 44 years (n = 23), and 13 studies targeted women only. In terms of study quality, 13 trials were rated as "strong", 15 as "moderate", and 7 studies as "weak". In addition, methodological quality of formal mediation analyses was "medium". Identified mediators for medium-/long-term weight control were higher levels of autonomous motivation, self-efficacy/barriers, self-regulation skills (such as self-monitoring), flexible eating restraint, and positive body image. For physical activity, significant putative mediators were high autonomous motivation, self-efficacy, and use of self-regulation skills. For dietary intake, the evidence was much less clear, and no consistent mediators were identified. Conclusions: This is the first systematic review of mediational psychological mechanisms of successful outcomes in obesity-related lifestyle change interventions. Despite limited evidence, higher autonomous motivation, self-efficacy, and self-regulation skills emerged as the best predictors of beneficial weight and physical activity outcomes; for weight control, positive body image and flexible eating restraint may additionally improve outcomes. These variables represent possible targets for future lifestyle interventions in overweight/obese populations.

BMC medicine · systematic review · 376 citationsread the source →

Quantifying the mental health burden of the most severe covid-19 restrictions: A natural experiment.

Background: The COVID-19 pandemic, and the restrictions required to halt spread of the infection, are associated with increased population burden of moderate to severe symptoms of depression and anxiety. The aim was to quantify the mental health burden of the most severe COVID-19 related restrictions. Methods: A natural experiment in which differences between Australian states and territories in the severity of restrictions for pandemic control, divided the population. People in Victoria experienced the most severe, and people in all other states and territories less severe or negligible restrictions. Data were collected in national, anonymously completed, online surveys (in April and in July / August 2020) of adults in Australia. Outcomes were, in the previous fortnight, experiencing clinically significant depressive symptoms (Patient Health Questionnaire 9 score ≥10); or symptoms of generalised anxiety (Generalised Anxiety Disorder Scale 7 score ≥10). Results: In total, 23,749 eligible respondents contributed complete data. There were no differences in the population burden of mental health problems between Victoria and the other states and territories at Survey One. By Survey Two prevalence rates of clinically significant depressive (Adjusted Odds Ratio (aOR) 1.96; 95% CI 1.62; 2.37) and anxiety (aOR 1.87; 95%CI 1.53; 2.29) symptoms were substantially and significantly higher in Victoria than in other states and territories. Limitations: Online surveys are less accessible to some groups of people. The data are self-report and not diagnostic. Conclusions: The most severe COVID-19 restrictions are associated with near double the population prevalence of moderate to severe depressive and generalised anxiety symptoms.

Journal of affective disorders · 41 citationsread the source →

Road traffic noise is associated with increased cardiovascular morbidity and mortality and all-cause mortality in London.

Aims: Road traffic noise has been associated with hypertension but evidence for the long-term effects on hospital admissions and mortality is limited. We examined the effects of long-term exposure to road traffic noise on hospital admissions and mortality in the general population. Methods and results: The study population consisted of 8.6 million inhabitants of London, one of Europe's largest cities. We assessed small-area-level associations of day- (7:00-22:59) and nighttime (23:00-06:59) road traffic noise with cardiovascular hospital admissions and all-cause and cardiovascular mortality in all adults (≥25 years) and elderly (≥75 years) through Poisson regression models. We adjusted models for age, sex, area-level socioeconomic deprivation, ethnicity, smoking, air pollution, and neighbourhood spatial structure. Median daytime exposure to road traffic noise was 55.6 dB. Daytime road traffic noise increased the risk of hospital admission for stroke with relative risk (RR) 1.05 [95% confidence interval (CI): 1.02-1.09] in adults, and 1.09 (95% CI: 1.04-1.14) in the elderly in areas >60 vs. <55 dB. Nighttime noise was associated with stroke admissions only among the elderly. Daytime noise was significantly associated with all-cause mortality in adults [RR 1.04 (95% CI: 1.00-1.07) in areas >60 vs. <55 dB]. Positive but non-significant associations were seen with mortality for cardiovascular and ischaemic heart disease, and stroke. Results were similar for the elderly. Conclusions: Long-term exposure to road traffic noise was associated with small increased risks of all-cause mortality and cardiovascular mortality and morbidity in the general population, particularly for stroke in the elderly.

European heart journal · 125 citationsread the source →

Lifestyle behaviour change for preventing the progression of chronic kidney disease: a systematic review.

Objectives: Modifying lifestyle can prevent the progression of chronic kidney disease (CKD) but the specific elements which lead to favourable behaviour change are not well understood. We aimed to identify and evaluate behaviour change techniques and functions in lifestyle interventions for preventing the progression of CKD. Design: Systematic review. Data sources: MEDLINE, EMBASE, CINAHL and PsycINFO. Eligibility criteria: Trials of lifestyle behaviour change interventions (including diet, physical activity, smoking and/or alcohol) published to September 2018 in adults with CKD stages 1-5. Data extraction and synthesis: Trial characteristics including population, sample size, study setting, intervention, comparator, outcomes and study duration, were extracted. Study quality was independently assessed by two reviewers using the Cochrane risk of bias tool. The Behaviour Change Technique Taxonomy v1 was used to identify behaviour change techniques (eg, goal setting) and the Health Behaviour Change Wheel was used to identify intervention functions (eg, education). Both were independently assessed by three reviewers. Results: In total, 26 studies involving 4263 participants were included. Risk of bias was high or unclear in most studies. Interventions involved diet (11), physical activity (8) or general lifestyle (7). Education was the most frequently used function (21 interventions), followed by enablement (18), training (12), persuasion (4), environmental restructuring (4), modelling (2) and incentivisation (2). The most common behaviour change techniques were behavioural instruction (23 interventions), social support (16), behavioural demonstration (13), feedback on behaviour (12) and behavioural practice/rehearsal (12). Eighteen studies (69%) showed a significant improvement in at least one primary outcome, all of which included education, persuasion, modelling and incentivisation. Conclusion: Lifestyle behaviour change interventions for CKD patients frequently used education, goal setting, feedback, monitoring and social support. The most promising interventions included education and used a variety of intervention functions (persuasion, modelling and incentivisation). Prospero registration number: CRD42019106053.

BMJ open · systematic review · 52 citationsread the source →

Twitter as a Tool for Health Research: A Systematic Review.

Background: Researchers have used traditional databases to study public health for decades. Less is known about the use of social media data sources, such as Twitter, for this purpose. Objectives: To systematically review the use of Twitter in health research, define a taxonomy to describe Twitter use, and characterize the current state of Twitter in health research. Search methods: We performed a literature search in PubMed, Embase, Web of Science, Google Scholar, and CINAHL through September 2015. Selection criteria: We searched for peer-reviewed original research studies that primarily used Twitter for health research. Data collection and analysis: Two authors independently screened studies and abstracted data related to the approach to analysis of Twitter data, methodology used to study Twitter, and current state of Twitter research by evaluating time of publication, research topic, discussion of ethical concerns, and study funding source. Main results: Of 1110 unique health-related articles mentioning Twitter, 137 met eligibility criteria. The primary approaches for using Twitter in health research that constitute a new taxonomy were content analysis (56%; n = 77), surveillance (26%; n = 36), engagement (14%; n = 19), recruitment (7%; n = 9), intervention (7%; n = 9), and network analysis (4%; n = 5). These studies collectively analyzed more than 5 billion tweets primarily by using the Twitter application program interface. Of 38 potential data features describing tweets and Twitter users, 23 were reported in fewer than 4% of the articles. The Twitter-based studies in this review focused on a small subset of data elements including content analysis, geotags, and language. Most studies were published recently (33% in 2015). Public health (23%; n = 31) and infectious disease (20%; n = 28) were the research fields most commonly represented in the included studies. Approximately one third of the studies mentioned ethical board approval in their articles. Primary funding sources included federal (63%), university (13%), and foundation (6%). Conclusions: We identified a new taxonomy to describe Twitter use in health research with 6 categories. Many data elements discernible from a user's Twitter profile, especially demographics, have been underreported in the literature and can provide new opportunities to characterize the users whose data are analyzed in these studies. Twitter-based health research is a growing field funded by a diversity of organizations. Public health implications. Future work should develop standardized reporting guidelines for health researchers who use Twitter and policies that address privacy and ethical concerns in social media research.

American journal of public health · systematic review · 368 citationsread the source →

Global, regional, and national incidence and mortality burden of non-COVID-19 lower respiratory infections and aetiologies, 1990-2021: a systematic analysis from the Global Burden of Disease Study 2021.

Background: Lower respiratory infections (LRIs) are a major global contributor to morbidity and mortality. In 2020-21, non-pharmaceutical interventions associated with the COVID-19 pandemic reduced not only the transmission of SARS-CoV-2, but also the transmission of other LRI pathogens. Tracking LRI incidence and mortality, as well as the pathogens responsible, can guide health-system responses and funding priorities to reduce future burden. We present estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 of the burden of non-COVID-19 LRIs and corresponding aetiologies from 1990 to 2021, inclusive of pandemic effects on the incidence and mortality of select respiratory viruses, globally, regionally, and for 204 countries and territories. Methods: We estimated mortality, incidence, and aetiology attribution for LRI, defined by the GBD as pneumonia or bronchiolitis, not inclusive of COVID-19. We analysed 26 259 site-years of mortality data using the Cause of Death Ensemble model to estimate LRI mortality rates. We analysed all available age-specific and sex-specific data sources, including published literature identified by a systematic review, as well as household surveys, hospital admissions, health insurance claims, and LRI mortality estimates, to generate internally consistent estimates of incidence and prevalence using DisMod-MR 2.1. For aetiology estimation, we analysed multiple causes of death, vital registration, hospital discharge, microbial laboratory, and literature data using a network analysis model to produce the proportion of LRI deaths and episodes attributable to the following pathogens: Acinetobacter baumannii, Chlamydia spp, Enterobacter spp, Escherichia coli, fungi, group B streptococcus, Haemophilus influenzae, influenza viruses, Klebsiella pneumoniae, Legionella spp, Mycoplasma spp, polymicrobial infections, Pseudomonas aeruginosa, respiratory syncytial virus (RSV), Staphylococcus aureus, Streptococcus pneumoniae, and other viruses (ie, the aggregate of all viruses studied except influenza and RSV), as well as a residual category of other bacterial pathogens. Findings: Globally, in 2021, we estimated 344 million (95% uncertainty interval [UI] 325-364) incident episodes of LRI, or 4350 episodes (4120-4610) per 100 000 population, and 2·18 million deaths (1·98-2·36), or 27·7 deaths (25·1-29·9) per 100 000. 502 000 deaths (406 000-611 000) were in children younger than 5 years, among which 254 000 deaths (197 000-320 000) occurred in countries with a low Socio-demographic Index. Of the 18 modelled pathogen categories in 2021, S pneumoniae was responsible for the highest proportions of LRI episodes and deaths, with an estimated 97·9 million (92·1-104·0) episodes and 505 000 deaths (454 000-555 000) globally. The pathogens responsible for the second and third highest episode counts globally were other viral aetiologies (46·4 million [43·6-49·3] episodes) and Mycoplasma spp (25·3 million [23·5-27·2]), while those responsible for the second and third highest death counts were S aureus (424 000 [380 000-459 000]) and K pneumoniae (176 000 [158 000-194 000]). From 1990 to 2019, the global all-age non-COVID-19 LRI mortality rate declined by 41·7% (35·9-46·9), from 56·5 deaths (51·3-61·9) to 32·9 deaths (29·9-35·4) per 100 000. From 2019 to 2021, during the COVID-19 pandemic and implementation of associated non-pharmaceutical interventions, we estimated a 16·0% (13·1-18·6) decline in the global all-age non-COVID-19 LRI mortality rate, largely accounted for by a 71·8% (63·8-78·9) decline in the number of influenza deaths and a 66·7% (56·6-75·3) decline in the number of RSV deaths. Interpretation: Substantial progress has been made in reducing LRI mortality, but the burden remains high, especially in low-income and middle-income countries. During the COVID-19 pandemic, with its associated non-pharmaceutical interventions, global incident LRI cases and mortality attributable to influenza and RSV declined substantially. Expanding access to health-care services and vaccines, including S pneumoniae, H influenzae type B, and novel RSV vaccines, along with new low-cost interventions against S aureus, could mitigate the LRI burden and prevent transmission of LRI-causing pathogens. Funding: Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care (UK).

The Lancet. Infectious diseases · systematic review · 388 citationsread the source →

Psychiatric and neuropsychiatric sequelae of COVID-19 - A systematic review.

It has become evident that coronavirus disease 2019 (COVID-19) has a multi-organ pathology that includes the brain and nervous system. Several studies have also reported acute psychiatric symptoms in COVID-19 patients. An increasing number of studies are suggesting that psychiatric deficits may persist after recovery from the primary infection. In the current systematic review, we provide an overview of the available evidence and supply information on potential risk factors and underlying biological mechanisms behind such psychiatric sequelae. We performed a systematic search for psychiatric sequelae in COVID-19 patients using the databases PubMed and Embase. Included primary studies all contained information on the follow-up period and provided quantitative measures of mental health. The search was performed on June 4th 2021. 1725 unique studies were identified. Of these, 66 met the inclusion criteria and were included. Time to follow-up ranged from immediately after hospital discharge up to 7 months after discharge, and the number of participants spanned 3 to 266,586 participants. Forty studies reported anxiety and/or depression, 20 studies reported symptoms- or diagnoses of post-traumatic stress disorder (PTSD), 27 studies reported cognitive deficits, 32 articles found fatigue at follow-up, and sleep disturbances were found in 23 studies. Highlighted risk factors were disease severity, duration of symptoms, and female sex. One study showed brain abnormalities correlating with cognitive deficits, and several studies reported inflammatory markers to correlate with symptoms. Overall, the results from this review suggest that survivors of COVID-19 are at risk of psychiatric sequelae but that symptoms generally improve over time.

Brain, behavior, and immunity · systematic review · 312 citationsread the source →

Identifying bereaved subjects at risk of complicated grief: Predictive value of questionnaire items in a cohort study.

Background: Bereavement is a condition which most people experience several times during their lives. A small but noteworthy proportion of bereaved individuals experience a syndrome of prolonged psychological distress in relation to bereavement. The aim of the study was to develop a clinical tool to identify bereaved individuals who had a prognosis of complicated grief and to propose a model for a screening tool to identify those at risk of complicated grief applicable among bereaved patients in general practice and palliative care. Methods: We examined the responses of 276 newly bereaved individuals to a variety of standardised and ad hoc questionnaire items eight weeks post loss. Inventory of Complicated Grief (ICG-R) was used as a gold standard of distress at six months after bereavement. Receiver operating characteristic (ROC) curves analysis was performed for all scales and items regarding ICG-R score. Sensitivity, specificity and area under curve (AUC) were calculated for scales and items with the most promising ROC curve analyses. Results: Beck's Depression Inventory (BDI) was the scale with the highest AUC (0.83) and adding a single item question ('Even while my relative was dying, I felt a sense of purpose in my life') gave a sensitivity of 80% and specificity of 75%. The positive/negative predictive values for this combination of questions were 70% and 85%, respectively. With this screening tool bereaved people could be categorized into three groups where group 1 had 7%, group 2 had 23% and group 3 had 64% propensity of suffering from complicated grief six months post loss. Conclusions: This study shows that the BDI in combination with a single item question eight weeks post loss may be used for clinical screening for risk of developing complicated grief after six months. The feasibility and clinical implications of the screening tool has to be tested in a clinical setting.

BMC palliative care · 30 citationsread the source →

Evaluation of Drinking Risk Levels as Outcomes in Alcohol Pharmacotherapy Trials: A Secondary Analysis of 3 Randomized Clinical Trials.

Importance: The US Food and Drug Administration recognizes total abstinence and no heavy drinking days as outcomes for pivotal pharmacotherapy trials for alcohol use disorder (AUD). Many patients have difficulty achieving these outcomes, which can discourage seeking treatment and has slowed the development of medications that affect alcohol use. Objective: To compare 2 drinking-reduction outcomes with total abstinence and no heavy drinking outcomes. Design, setting, and participants: Data were obtained from 3 multisite, randomized, placebo-controlled clinical trials of medications for treating alcohol dependence (naltrexone, varenicline, and topiramate) in adults with DSM-IV-categorized alcohol dependence. Main outcomes and measures: Within each trial, the percentage of participants in active and placebo conditions who met responder definitions of abstinence, no heavy drinking days, a WHO 1-level reduction, and a WHO 2-level reduction was computed by month with corresponding effect sizes (Cohen h). Results: Across the 3 trials (N = 1169; mean [SD] age, 45 [10] years; 824 [70.5%] men), the percentage of participants classified as responders during the last 4 weeks of treatment was lowest for abstinence (naltrexone, 34.7% [100 of 288]; varenicline, 7.3% [7 of 96]; topiramate, 11.7% [21 of 179]) followed by no heavy drinking days (naltrexone, 51.0% [147 of 288]; varenicline, 24.0% [23 of 96]; topiramate, 20.7% [37 of 179]), WHO 2-level reduction (naltrexone, 75.0% [216 of 288]; varenicline, 55.2% [53 of 96]; topiramate, 44.7% [80 of 179]), and WHO 1-level reduction (naltrexone, 83.3% [240 of 288]; varenicline, 69.8 [67 of 96]; topiramate, 54.7% [98 of 179]) outcomes. Standardized treatment effects observed for the WHO 2-level reduction outcomes (naltrexone, Cohen h = 0.214 [95% CI, 0.053 -0.375]; varenicline, 0.273 [95% CI, -0.006 to 0.553]; topiramate, 0.230 [95% CI, 0.024-0.435]) and WHO 1-level reduction (naltrexone, Cohen h = 0.116 [95% CI, -0.046 to 0.277]; varenicline, 0.338 [95% CI, 0.058-0.617]; topiramate, 0.014 [95% CI, -0.192 to 0.219]) were comparable with those obtained using abstinence (naltrexone, Cohen h = 0.142 [95% CI, -0.020 to 0.303]; varenicline, 0.146 [95% CI, -0.133 to 0.426]; topiramate, 0.369 [95% CI, 0.163-0.574]) and no heavy drinking days (naltrexone, Cohen h = 0.140 [95% CI, -0.021 to 0.302]; varenicline, 0.232 [95% CI, -0.048 to 0.511]; topiramate, 0.207 [95% CI, 0.002-0.413]). Conclusions and relevance: WHO drinking risk level reductions appear to be worthwhile indicators of treatment outcome in AUD pharmacotherapy trials. These outcomes may align with drinking reduction goals of many patients and capture clinically meaningful improvements experienced by more patients than either abstinence or no heavy drinking days. Trial registration: ClinicalTrials.gov identifiers: NCT00006206; NCT01146613; NCT00210925.

JAMA psychiatry · randomised controlled trial · 98 citationsread the source →

A task-shared, collaborative care psychosocial intervention for improving depressive symptomatology among older adults in a socioeconomically deprived area of Brazil (PROACTIVE): a pragmatic, two-arm, parallel-group, cluster-randomised controlled trial.

Background: There is an urgent need to reduce the burden of depression among older adults in low-income and middle-income countries (LMICs). We aimed to evaluate the efficacy of a task-shared, collaborative care psychosocial intervention for improving recovery from depression in older adults in Brazil. Methods: PROACTIVE was a pragmatic, two-arm, parallel-group, cluster-randomised controlled trial conducted in Guarulhos, Brazil. Primary care clinics (clusters) were stratified by educational level and randomly allocated (1:1) to either enhanced usual care alone (control group) or to enhanced usual care plus the psychosocial intervention (intervention group), which involved a 17-week psychosocial programme based on psychoeducation and behavioural activation approaches. Individuals approached for the initial screening assessment were selected randomly from a list of individuals provided by the Health Secretariat of Guarulhos. Face-to-face baseline assessments were conducted among adults aged 60 years or older registered with one of the primary care clinics and identified with clinically significant depressive symptomatology (9-item Patient Health Questionnaire [PHQ-9] score ≥10). Community health workers delivered the programme through home sessions, supported by a dedicated tablet application. Masking of clinic staff and community health workers who delivered the intervention was not feasible; however, research assistants conducting recruitment and follow-up assessments were masked to trial allocation. The primary outcome was recovery from depression (PHQ-9 score <10) at 8-month follow-up. All primary analyses were performed by intention to treat with imputed data. Adaptations to the protocol were made due to the COVID-19 pandemic; recruitment and intervention home sessions were stopped, and follow-up assessments were conducted by telephone. This trial is registered with the ISRCTN registry, ISRCTN57805470. Findings: We identified 24 primary care clinics in Guarulhos that were willing to participate, of which 20 were randomly allocated to either the control group (ten [50%] clusters) or to the intervention group (ten [50%] clusters). The four remaining eligible clusters were kept as reserves. Between May 23, 2019, and Feb 21, 2020, 8146 individuals were assessed for eligibility, of whom 715 (8·8%) participants were recruited: 355 (49·7%) in the control group and 360 (50·3%) in the intervention group. 284 (80·0%) participants in the control group and 253 (70·3%) in the intervention group completed follow-up at 8 months. At 8-month follow-up, 158 (62·5%) participants in the intervention group showed recovery from depression (PHQ-9 score <10) compared with 125 (44·0%) in the control group (adjusted odds ratio 2·16 [95% CI 1·47-3·18]; p<0·0001). These findings were maintained in the complete case analysis. No adverse events related to the intervention were observed. Interpretation: Although the COVID-19 pandemic altered delivery of the intervention, the low-intensity psychosocial intervention delivered mainly by non-mental health professionals was highly efficacious in improving recovery from depression in older adults in Brazil. Our results support a low-resource intervention that could be useful to reduce the treatment gap for depression among older people in other LMICs. Funding: São Paulo Research Foundation and Joint Global Health Trials (UK Department for International Development, Medical Research Council, and the Wellcome Trust).

The lancet. Healthy longevity · randomised controlled trial · 25 citationsread the source →

REFOCUS-PULSAR recovery-oriented practice training in specialist mental health care: a stepped-wedge cluster randomised controlled trial.

Background: Recovery-oriented practice promotes the strengths and recovery potential of individuals. We aimed to establish whether individuals who access mental health services where staff have received the REFOCUS-PULSAR intervention, an adaptation of the UK's REFOCUS recovery-oriented staff intervention for use in Australia, show increased recovery compared with people using non-intervention services. Methods: We did a pragmatic, two-step, stepped-wedge, randomised controlled trial at 18 sites grouped into 14 clusters across public mental health services and mental health community support services in Victoria, Australia. Eligible staff were working part-time or full-time in a direct service role at one of the 18 sites and had consumers being recruited for this study. Eligible consumers were receiving care from a participating cluster, with contact in the 3 months before data collection; aged 18-75 years; and not imprisoned. Clusters were randomly assigned with a web-based randomisation tool to receive the REFOCUS-PULSAR intervention in either the first year (step one) or second year (step two). Consumers, but not staff, were masked to treatment assignment. The primary outcome was the Questionnaire about the Process of Recovery (QPR), for which cross-sectional data were collected across three timepoints (baseline [T0], year 1 [T1], and year 2 [T2]). The primary analysis was done by intention to treat. This trial is registered with ANZCTR, number ACTRN12614000957695. Findings: 190 staff (111 from public mental health services and 79 from mental health community support services) received the REFOCUS-PULSAR recovery-oriented training intervention. Between Sept 18, 2014, and May 19, 2017, 942 consumers were recruited across the three timepoints (T0: n=301; T1: n=334; T2: n=307). The mean QPR score was 53·6 (SD 16·3) in the control group and 54·4 (16·2) in the intervention group (adjusted difference 3·7, 95% CI 0·5-6·8; p=0·023). The Cohen's d value for the intervention effect was small (d=0·23). Interpretation: The REFOCUS-PULSAR intervention had a small but significant effect on the QPRs of individuals using community mental health services and might be effective in promotion of recovery-oriented practice across sectors. Funding: Victorian Government Mental Illness Research Fund.

The lancet. Psychiatry · randomised controlled trial · 39 citationsread the source →

Effect of Prefrontal Cortex Stimulation on Regulation of Amygdala Response to Threat in Individuals With Trait Anxiety: A Randomized Clinical Trial.

Importance: Transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) is under clinical investigation as a treatment for major depressive disorder. However, the mechanisms of action are unclear, and there is a lack of neuroimaging evidence, particularly among individuals with affective dysfunction. Furthermore, there is no direct causal evidence among humans that the prefrontal-amygdala circuit functions as described in animal models (ie, that increasing activity in prefrontal cortical control regions inhibits amygdala response to threat). Objective: To determine whether stimulation of the prefrontal cortex reduces amygdala threat reactivity in individuals with trait anxiety. Design, setting, and participants: This community-based randomized clinical trial used a double-blind, within-participants design (2 imaging sessions per participant). Eighteen women with high trait anxiety (age range, 18-42 years) who scored greater than 45 on the trait measure of State-Trait Anxiety Inventory were randomized to receive active or sham tDCS of the DLPFC during the first session and the other intervention during the next session. Each intervention was followed immediately by a functional imaging scan during which participants performed an attentional task requiring them to ignore threatening face distractors. Data were collected from May 7 to October 6, 2015. Main outcomes and measures: Amygdala threat response, measured with functional magnetic resonance imaging. Results: Data from 16 female participants (mean age, 23 years; range, 18-42 years), with 8 in each group, were analyzed. Compared with sham stimulation, active DLPFC stimulation significantly reduced bilateral amygdala threat reactivity (z = 3.30, P = .04) and simultaneously increased activity in cortical regions associated with attentional control (z = 3.28, P < .001). In confirmatory behavioral analyses, there was a mean improvement in task accuracy of 12.2% (95% CI, 0.30%-24.0%; mean [SD] difference in number of correct answers, 2.2 [4.5]; t15 = 1.94, P = .04) after active DLPFC stimulation. Conclusions and relevance: These results reveal a causal role for prefrontal regulation of amygdala function in attentional capture by threat in individuals with high trait anxiety. The finding that prefrontal stimulation acutely increases attentional control signals and reduces amygdala threat reactivity may indicate a neurocognitive mechanism that could contribute to tDCS treatment effects in affective disorders. Trial registration: isrctn.org Identifier: ISRCTN78638425.

JAMA psychiatry · randomised controlled trial · 102 citationsread the source →

Attention Bias Modification training in individuals with depressive symptoms: A randomized controlled trial.

Background and objectives: Negative attentional biases are often considered to have a causal role in the onset and maintenance of depressive symptoms. This suggests that reduction of such biases may be a plausible strategy in the treatment of depressive symptoms. The present clinical randomized controlled trial examined long-term effects of a computerized attention bias modification (ABM) procedure on individuals with elevated depressive symptoms. Methods: In a double-blind study design, 77 individuals with ongoing mild to severe symptoms of depression were randomly assigned to one of three conditions: 1) ABM training (n = 27); 2) placebo (n = 27); 3) assessment-only (n = 23). In both the ABM and placebo conditions, participants completed 8 sessions of 216-trials (1728 in total) during a 2-week period. Assessments were conducted at pre-training and post-training (0, 2, 4, 8-week, 3, 7-month follow-ups). Change in depressive symptoms and restoration of asymptomatic level were the primary outcome measures. Results: In the ABM, but not the other two conditions, significant reductions in depressive symptoms were found at post-training and maintained during the 3-month follow-up. Importantly, more participants remained asymptomatic in the ABM condition, as compared to the other two conditions, from post-training to 7-month follow-up. ABM also significantly reduced secondary outcome measures including rumination and trait anxiety, and notably, the ABM effect on reducing depressive symptoms was mediated by rumination. Limitation: Generalization of the findings may be limited because the present sample included only college students. Conclusions: The ABM effect on reducing depressive symptoms was maintained for at least 3-month duration in individuals with elevated depressive symptoms, and these results suggest that ABM may be a useful tool for the prevention of depressive symptoms. CLINICALTRIALS.GOV: NCT01628016.

Journal of behavior therapy and experimental psychiatry · randomised controlled trial · 91 citationsread the source →

Efficacy of cognitive behavioural therapy for sleep improvement in patients with persistent delusions and hallucinations (BEST): a prospective, assessor-blind, randomised controlled pilot trial.

Background: Sleep disturbance occurs in most patients with delusions or hallucinations and should be treated as a clinical problem in its own right. However, cognitive behavioural therapy (CBT)-the best evidence-based treatment for insomnia-has not been tested in this patient population. We aimed to pilot procedures for a randomised trial testing CBT for sleep problems in patients with current psychotic experiences, and to provide a preliminary assessment of potential benefit. Methods: We did this prospective, assessor-blind, randomised controlled pilot trial (Better Sleep Trial [BEST]) at two mental health centres in the UK. Patients (aged 18-65 years) with persistent distressing delusions or hallucinations in the context of insomnia and a schizophrenia spectrum diagnosis were randomly assigned (1:1), via a web-based randomisation system with minimisation to balance for sex, insomnia severity, and psychotic experiences, to receive either eight sessions of CBT plus standard care (medication and contact with the local clinical team) or standard care alone. Research assessors were masked to group allocation. Assessment of outcome was done at weeks 0, 12 (post-treatment), and 24 (follow-up). The primary efficacy outcomes were insomnia assessed by the Insomnia Severity Index (ISI) and delusions and hallucinations assessed by the Psychotic Symptoms Rating Scale (PSYRATS) at week 12. We did analysis by intention to treat, with an aim to provide confidence interval estimation of treatment effects. This study is registered with ISRCTN, number 33695128. Findings: Between Dec 14, 2012, and May 22, 2013, and Nov 7, 2013, and Aug 26, 2014, we randomly assigned 50 patients to receive CBT plus standard care (n=24) or standard care alone (n=26). The last assessments were completed on Feb 10, 2015. 48 (96%) patients provided follow-up data. 23 (96%) patients offered CBT took up the intervention. Compared with standard care, CBT led to reductions in insomnia in the large effect size range at week 12 (adjusted mean difference 6.1, 95% CI 3.0-9.2, effect size d=1.9). By week 12, nine (41%) of 22 patients receiving CBT and one (4%) of 25 patients receiving standard care alone no longer had insomnia, with ISI scores lower than the cutoff for insomnia. The treatment effect estimation for CBT covered a range from reducing but also increasing delusions (adjusted mean difference 0.3, 95% CI -2.0 to 2.6) and hallucinations (-1.9, -6.5 to 2.7). Three patients, all in the CBT group, had five adverse events, although none were regarded as related to study treatment. Interpretation: Our findings show that CBT for insomnia might be highly effective for improving sleep in patients with persistent delusions or hallucinations. A larger, suitably powered phase 3 study is now needed to provide a precise estimate of the effects of CBT for sleep problems, both on sleep and psychotic experiences. Funding: Research for Patient Benefit Programme, National Institute for Health Research.

The lancet. Psychiatry · randomised controlled trial · 160 citationsread the source →

Standardized Rehabilitation and Hospital Length of Stay Among Patients With Acute Respiratory Failure: A Randomized Clinical Trial.

Importance: Physical rehabilitation in the intensive care unit (ICU) may improve the outcomes of patients with acute respiratory failure. Objective: To compare standardized rehabilitation therapy (SRT) to usual ICU care in acute respiratory failure. Design, setting, and participants: Single-center, randomized clinical trial at Wake Forest Baptist Medical Center, North Carolina. Adult patients (mean age, 58 years; women, 55%) admitted to the ICU with acute respiratory failure requiring mechanical ventilation were randomized to SRT (n=150) or usual care (n=150) from October 2009 through May 2014 with 6-month follow-up. Interventions: Patients in the SRT group received daily therapy until hospital discharge, consisting of passive range of motion, physical therapy, and progressive resistance exercise. The usual care group received weekday physical therapy when ordered by the clinical team. For the SRT group, the median (interquartile range [IQR]) days of delivery of therapy were 8.0 (5.0-14.0) for passive range of motion, 5.0 (3.0-8.0) for physical therapy, and 3.0 (1.0-5.0) for progressive resistance exercise. The median days of delivery of physical therapy for the usual care group was 1.0 (IQR, 0.0-8.0). Main outcomes and measures: Both groups underwent assessor-blinded testing at ICU and hospital discharge and at 2, 4, and 6 months. The primary outcome was hospital length of stay (LOS). Secondary outcomes were ventilator days, ICU days, Short Physical Performance Battery (SPPB) score, 36-item Short-Form Health Surveys (SF-36) for physical and mental health and physical function scale score, Functional Performance Inventory (FPI) score, Mini-Mental State Examination (MMSE) score, and handgrip and handheld dynamometer strength. Results: Among 300 randomized patients, the median hospital LOS was 10 days (IQR, 6 to 17) for the SRT group and 10 days (IQR, 7 to 16) for the usual care group (median difference, 0 [95% CI, -1.5 to 3], P = .41). There was no difference in duration of ventilation or ICU care. There was no effect at 6 months for handgrip (difference, 2.0 kg [95% CI, -1.3 to 5.4], P = .23) and handheld dynamometer strength (difference, 0.4 lb [95% CI, -2.9 to 3.7], P = .82), SF-36 physical health score (difference, 3.4 [95% CI, -0.02 to 7.0], P = .05), SF-36 mental health score (difference, 2.4 [95% CI, -1.2 to 6.0], P = .19), or MMSE score (difference, 0.6 [95% CI, -0.2 to 1.4], P = .17). There were higher scores at 6 months in the SRT group for the SPPB score (difference, 1.1 [95% CI, 0.04 to 2.1, P = .04), SF-36 physical function scale score (difference, 12.2 [95% CI, 3.8 to 20.7], P = .001), and the FPI score (difference, 0.2 [95% CI, 0.04 to 0.4], P = .02). Conclusions and relevance: Among patients hospitalized with acute respiratory failure, SRT compared with usual care did not decrease hospital LOS. Trial registration: clinicaltrials.gov Identifier: NCT00976833.

JAMA · randomised controlled trial · 299 citationsread the source →

Circumcision versus preputioplasty for balanitis xerotica obliterans: a randomised controlled feasibility trial.

Objectives: To determine: (i) feasibility for a randomised controlled trial (RCT) comparing circumcision to preputioplasty and intralesional triamcinolone (PIT) to treat balanitis xerotica obliterans (BXO) and (ii) patient outcomes to inform future study design. Patients and methods: Approval was obtained from the UK Health Research Authority and local Research Ethics Committee (Reference 16/NW/0364) and the trial protocol registered with ClinicalTrials.gov (NCT02854995). A total of 20 boys (aged 2-16 years) with BXO were randomised to either circumcision or PIT (online parallel group 1:1 allocation, non-blinded). Exclusion criteria were: (i) previous penile surgery and (ii) contraindication for either treatment. Follow-up (including satisfaction questionnaire) was at 6 weeks, 3 and 12 months. Data are presented as median (interquartile range [IQR]), continuous variables were compared by t-test. Results: A total of 54 boys were approached over 18 months: 23 (45%) were recruited and randomised. The commonest reason for non-entry was treatment preference: 12 preferred circumcision, 18 preferred PIT. Four patients withdrew after randomisation, three did not want circumcision and one did not want PIT. The groups were similar in terms of age (median [IQR] 11 [6-12] vs 8 [7-10] years, P = 0.53) and duration of symptoms (median [IQR] 6 [6-15] vs 6 [2-24] months, P = 0.77). There were no protocol breaches, serious adverse events or postoperative meatal stenosis. There was one self-resolving haematoma after PIT and one suture granuloma after circumcision. Two boys went on to have a circumcision after PIT. Overall, satisfaction levels were high for both groups. Conclusion: A definitive RCT of circumcision vs PIT for BXO appears feasible, with 39% of those approached completing the trial. More families preferred PIT. A robust comparison in the form of a multicentred RCT is required.

BJU international · randomised controlled trial · 5 citationsread the source →