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Populations and Interventions for Palliative and End-of-Life Care: A Systematic Review.

Importance: Evidence supports palliative care effectiveness. Given workforce constraints and the costs of new services, payers and providers need help to prioritize their investments. They need to know which patients to target, which personnel to hire, and which services best improve outcomes. Objective: To inform how payers and providers should identify patients with "advanced illness" and the specific interventions they should implement, we reviewed the evidence to identify (1) individuals appropriate for palliative care and (2) elements of health service interventions (personnel involved, use of multidisciplinary teams, and settings of care) effective in achieving better outcomes for patients, caregivers, and the healthcare system. Evidence review: Systematic searches of MEDLINE, EMBASE, PsycINFO, Web of Science, and Cochrane Database of Systematic Reviews databases (1/1/2001-1/8/2015). Results: Randomized controlled trials (124) met inclusion criteria. The majority of studies in cancer (49%, 38 of 77 studies) demonstrated statistically significant patient or caregiver outcomes (e.g., p < 0.05), as did those in congestive heart failure (CHF) (62%, 13 of 21), chronic obstructive pulmonary disease (COPD; 58%, 11 of 19), and dementia (60%, 15 of 25). Most prognostic criteria used clinicians' judgment (73%, 22 of 30). Most interventions included a nurse (70%, 69 of 98), and many were nurse-only (39%, 27 of 69). Social workers were well represented, and home-based approaches were common (56%, 70 of 124). Home interventions with visits were more effective than those without (64%, 28 of 44; vs. 46%, 12 of 26). Interventions improved communication and care planning (70%, 12 of 18), psychosocial health (36%, 12 of 33, for depressive symptoms; 41%, 9 of 22, for anxiety), and patient (40%, 8 of 20) and caregiver experiences (63%, 5 of 8). Many interventions reduced hospital use (65%, 11 of 17), but most other economic outcomes, including costs, were poorly characterized. Palliative care teams did not reliably lower healthcare costs (20%, 2 of 10). Conclusions: Palliative care improves cancer, CHF, COPD, and dementia outcomes. Effective models include nurses, social workers, and home-based components, and a focus on communication, psychosocial support, and the patient or caregiver experience. High-quality research on intervention costs and cost outcomes in palliative care is limited.

Journal of palliative medicine · systematic review · 135 citationsread the source →

Acute and long-term safety and tolerability of risperidone in children with autism.

Treatment-emergent adverse events (AEs) were monitored during an 8-week, double-blind, placebo-controlled trial of risperidone (0.5-3.5 mg/day) in 101 children and adolescents with a lifetime diagnosis of autistic disorder. In addition, 37 placebo nonresponders received open-label risperidone for another 8 weeks. Of all the risperidone responders (n=65), 63 entered an open extension of another 16 weeks (6 months total risperidone exposure), and 32 of them were rerandomized to either continued risperidone therapy (n=16) or gradual replacement with placebo (n=16) over 8 weeks. We collected the following measures of safety and tolerability: (1) laboratory blood assessments (CBC with differential, electrolytes, and liver function tests) and urinalyses, (2) vital signs, (3) Side Effects Review of AEs thought to be associated with risperidone, (4) sleep records, (5) Simpson Angus Neurological Rating Scale (SARS), (6) Abnormal Involuntary Movement Scale (AIMS), and (7) height and weight. No clinically significant changes were found on the lab tests. During the 8-week acute trial, the most common AEs on the Side Effects Review, scored as moderate or higher, were as follows (placebo and risperidone, respectively): Somnolence (12% and 37%), enuresis (29% and 33%), excessive appetite (10% and 33%), rhinitis (8% and 16%), difficulty waking (8% and 12%), and constipation (12% and 10%). "Difficulty falling asleep" and anxiety actually favored the risperidone condition at statistically significant levels. The same AEs tended to recur through 6 months of treatment, although often at reduced levels. Using Centers for Disease Control (CDC) standardized scores, both weight and body mass index (BMI) increased with risperidone during the acute trial (0.5 and 0.6 SDs, respectively, for risperidone; 0.0 and 0.1 SDs, respectively, for placebo) and into open-label extension (0.19 and 0.16 SDs, respectively), although the amount of gain decelerated with time. Extrapyramidal symptoms, as assessed by the SARS, were no more common for drug than placebo, although drooling was reported more often in the risperidone group. There were no differences between groups on the AIMS. Two subjects had seizures (one taking placebo), but these were considered unrelated to active drug. Most AEs were mild to moderate and failed to interfere with therapeutic changes; there were no unanticipated AEs. The side effects of most concern were somnolence and weight gain.

Journal of child and adolescent psychopharmacology · randomised controlled trial · 92 citationsread the source →

User-Centered App Adaptation of a Low-Intensity E-Mental Health Intervention for Syrian Refugees.

Introduction: The aim of this study is to describe the initial stages of the iterative and user-centered mobile mental health adaptation process of Step-by-Step (SbS), a modularized and originally web-based e-mental health intervention developed by the World Health Organization (WHO). Given the great need for improving the responsiveness and accessibility of health systems in host countries, the EU-funded STRENGTHS consortium studies the adaptation, implementation and scaling-up of SbS for Syrian refugees in Germany, Sweden and Egypt. Using early prototyping, usability testing and identification of barriers to implementation, the study demonstrates a user-centered process of contextual adaptation to the needs and expectations of Syrian refugees. Materials and Methods: N = 128 adult Syrian refugees residing in Germany, Sweden and Egypt took part in qualitative assessments. Access, usage, and potential barriers regarding information and communication technologies (ICTs) were assessed in free list interviews. Interactive prototypes of the app were presented in key informant interviews and evaluated on usability, user experience and dissemination strategies. Focus groups were conducted to verify the results. The interview protocols were analyzed using inductive and deductive thematic analysis. Results: The use of digital technologies was found to be widespread among Syrian refugees. Technical literacy and problems with accessing the internet were common barriers. The majority of the respondents reacted positively to the presented app prototypes, stressing the potential health impact of the intervention (n = 28; 78%), its flexibility and customizability (n = 19; 53%) as well as the easy learnability of the app (n = 12; 33%). Aesthetic components (n = 12; 33%) and the overall length and pace of the intervention sessions (n = 9; 25%) were criticized in regard to their negative impact on user motivation. Acceptability, credibility, and technical requirements were identified as main barriers to implementation. Discussion: The study provided valuable guidance for adapting the app version of SbS and for mobile mental health adaptation in general. The findings underline the value of contextual adaptation with a focus on usability, user experience, and context specific dissemination strategies. Related factors such as access, acceptability and adherence have major implications for scaling-up digital interventions.

Frontiers in psychiatry · 87 citationsread the source →

A meta-analysis of nutrition interventions on mental development of children under-two in low- and middle-income countries.

Interventions to improve nutritional status of young children in low- and middle-income countries (LMIC) may have the added benefit of improving their mental and motor development. This meta-analysis updates and goes beyond previous ones by answering two important questions: (1) do prenatal and postnatal nutritional inputs improve mental development, and (2) are effects on mental development associated with two theoretically interesting mediators namely physical growth and motor development? The meta-analysis of articles on Medline, PsycINFO, Global Health and Embase was limited to randomized trials in LMICs, with mental development of children from birth to age two years as an outcome. The initial yield of 2689 studies was reduced to 33; 12 received a global quality rating of strong. Of the 10 prenatal and 23 postnatal nutrition interventions, the majority used zinc, iron/folic acid, vitamin A or multiple micronutrients, with a few evaluating macronutrients. The weighted mean effect size, Cohen's d (95% CI) for prenatal and postnatal nutrition interventions on mental development was 0.042 (-0.0084, 0.092) and 0.076 (0.019, 0.13), respectively. Postnatal supplements consisting of macronutrients yielded an effect size d (95% CI) of 0.14 (0.0067, 0.27), multiple micronutrients 0.082 (-0.012, 0.18) and single micronutrients 0.058 (-0.0015, 0.12). Motor development, but not growth status, effect sizes were significantly associated with mental development in postnatal interventions. In summary, nutrition interventions had small effects on mental development. Future studies might have greater effect if they addressed macronutrient deficiencies combined with child stimulation and hygiene and sanitation interventions.

Maternal & child nutrition · meta-analysis · 64 citationsread the source →

Impact of the COVID-19 pandemic on suicidal attempts and death rates: a systematic review.

Background: The COVID-19 pandemic has exacerbated the risk factors associated with suicidal behavior and thus, prioritizing its prevention is recommended. Methods: This study systematically reviewed the global evidence on the incidence of suicide/suicidal attempts and the trend in suicidal rates during the COVID-19 pandemic. Cross-sectional and cohort studies investigating the outcomes of suicidal death and suicidal attempts at any setting during the COVID-19 pandemic were searched in Medline, Embase, and PsycINFO databases for papers published from December 2019 to May 2021. Results: Out of 1052 studies18 studies with 12,746 suicidal attempts and 33,345 suicidal deaths were included in the final analysis. The mental health impact of social distancing, COVID-19 quarantine, and financial crises due to loss of employment were associated risk factors with suicide and/or suicidal attempts during the COVID-19 pandemic. Six common thematic recommendations for preventing suicidal deaths and suicidal attempts were identified. Conclusions: Unexpected behavior changes during the COVID-19 pandemic may have contributed to the increasing trend of suicidal attempts reported. Domestic conflicts and violence, financial loss, anxiety and depression, and pre-existing mental health condition/s should be considered in preventing suicidal attempts and deaths secondary to the COVID 19 pandemic. Early detection and timely intervention for individuals with suicidal behavior is crucial and collated recommendations in the current study can be utilized for those preventive interventions. More systematic suicide risk screening process should be introduced who are at risk, along with an evidence base prevention approach.

BMC psychiatry · systematic review · 82 citationsread the source →

Tenofovir-diphosphate in peripheral blood mononuclear cells during low, medium and high adherence to emtricitabine/ tenofovir alafenamide vs. emtricitabine/ tenofovir disoproxil fumarate.

Objective: Tenofovir alafenamide (TAF) preferentially loads peripheral blood mononuclear cells (PBMCs), resulting in higher PBMC tenofovir-diphosphate (TFV-DP) vs. tenofovir disoproxil fumarate (TDF). No studies have yet compared TFV-DP in PBMC from lower than daily dosing between prodrugs, which has potential implications for event-driven preexposure prophylaxis and pharmacologic forgiveness. Design: Two separate randomized, directly observed therapy (DOT) crossover studies (DOT-DBS and TAF-DBS) were conducted to mimic low, medium and high adherence. Methods: HIV-negative adults were randomized to two 12-week DOT regimens of 33, 67 or 100% of daily dosing with emtricitabine (F)/TAF 200 mg/25 mg (TAF-DBS) or F/TDF 200 mg/300 mg (DOT-DBS), separated by a 12-week washout. PBMC steady-state concentrations (Css) of TFV-DP and FTC-TP were estimated using nonlinear mixed models and compared between F/TAF and F/TDF. Results: Thirty-five participants contributed to 33% (n = 23), 67% (n = 23) and 100% (n = 23) of daily F/TAF regimens. Forty-four contributed to 33% (n = 15), 67% (n = 16) and 100% (n = 32) of daily F/TDF regimens. PBMC TFV-DP Css were 7.3 [95% confidence interval (95% CI): 6.4-8.2], 7.1 (5.9-8.2) and 6.7- (4.4-8.9) fold higher (P < 0.0001) following F/TAF vs. F/TDF; 593 vs. 81.7, 407 vs. 57.4, and 215 vs. 32.3 fmol/106 cells, respectively. TFV-DP was 2.6 (2.1-3.1) fold higher with 33% F/TAF vs. 100% F/TDF. Estimated half-lives (95% CI) of TFV-DP in PBMC were 2.9 (1.5-5.5) days for F/TAF and 2.1 (1.5-2.9) days for F/TDF. FTC-TP was similar in both studies (P = 0.119). Conclusion: F/TAF produced 6.7 to 7.3-fold higher TFV-DP in PBMC vs. F/TDF across adherence levels, supporting increased potency and pharmacologic forgiveness with F/TAF in the PBMC compartment.

AIDS (London, England) · randomised controlled trial · 27 citationsread the source →

Prevalence of depression, anxiety, and insomnia among healthcare workers during the COVID-19 pandemic: A systematic review and meta-analysis.

Background: COVID-19 pandemic has the potential to significantly affect the mental health of healthcare workers (HCWs), who stand in the frontline of this crisis. It is, therefore, an immediate priority to monitor rates of mood, sleep and other mental health issues in order to understand mediating factors and inform tailored interventions. The aim of this review is to synthesize and analyze existing evidence on the prevalence of depression, anxiety and insomnia among HCWs during the Covid-19 outbreak. Methods: A systematic search of literature databases was conducted up to April 17th, 2020. Two reviewers independently assessed full-text articles according to predefined criteria. Risk of bias for each individual study was assessed and data pooled using random-effects meta-analyses to estimate the prevalence of specific mental health problems. The review protocol is registered in PROSPERO and is available online. Findings: Thirteen studies were included in the analysis with a combined total of 33,062 participants. Anxiety was assessed in 12 studies, with a pooled prevalence of 23·2% and depression in 10 studies, with a prevalence rate of 22·8%. A subgroup analysis revealed gender and occupational differences with female HCPs and nurses exhibiting higher rates of affective symptoms compared to male and medical staff respectively. Finally, insomnia prevalence was estimated at 38·9% across 5 studies. Interpretation: Early evidence suggests that a considerable proportion of HCWs experience mood and sleep disturbances during this outbreak, stressing the need to establish ways to mitigate mental health risks and adjust interventions under pandemic conditions.

Brain, behavior, and immunity · meta-analysis · 2357 citationsread the source →

Donepezil for dementia with Lewy bodies: a randomized, placebo-controlled trial.

Objective: Because cholinergic deficits are prominent in dementia with Lewy bodies (DLB), we investigated the effects of a cholinesterase inhibitor, donepezil, in such patients in a randomized, double-blind, placebo-controlled exploratory phase 2 trial. Methods: One-hundred forty patients with DLB, recruited from 48 specialty centers in Japan, were randomly assigned to receive placebo or 3, 5, or 10 mg of donepezil hydrochloride daily for 12 weeks (n = 35, 35, 33, and 37, respectively). Effects on cognitive function were assessed using the Mini-Mental State Examination (MMSE) and several domain-specific neuropsychological tests. Changes in behavior were evaluated using the Neuropsychiatric Inventory, caregiver burden using the Zarit Caregiver Burden Interview, and global function using the Clinician's Interview-Based Impression of Change-plus Caregiver Input (CIBIC-plus). Safety measures included the Unified Parkinson's Disease Rating Scale part III. Results: Donepezil at 5 and 10 mg/day was significantly superior to placebo on both the MMSE (5 mg: mean difference, 3.8; 95% confidence interval [CI], 2.3-5.3; p < 0.001; 10 mg: mean difference, 2.4; 95% CI, 0.9-3.9; p = 0.001) and CIBIC-plus (p < 0.001 for each); 3 mg/day was significantly superior to placebo on CIBIC-plus (p < 0.001), but not on the MMSE (p = 0.017). Significant improvements were found also in behavioral measures (p < 0.001) at 5 and 10 mg/day and caregiver burden (p = 0.004) at 10 mg/day. The safety results were consistent with the known profile of donepezil and similar among groups. Interpretation: Donepezil at 5 and 10mg/day produces significant cognitive, behavioral, and global improvements that last at least 12 weeks in DLB patients, reducing caregiver burden at the highest dose. Donepezil is safe and well tolerated.

Annals of neurology · randomised controlled trial · 173 citationsread the source →

Joblessness and Lost Earnings after Acute Respiratory Distress Syndrome in a 1-Year National Multicenter Study.

Rationale: Following acute respiratory distress syndrome (ARDS), joblessness is common but poorly understood. Objectives: To evaluate the timing of return to work after ARDS, and associated risk factors, lost earnings, and changes in healthcare coverage Methods: Over 12-month longitudinal follow-up, ARDS survivors from 43 U.S. ARDSNet hospitals provided employment and healthcare coverage data via structured telephone interviews. Factors associated with the timing of return to work were assessed using Fine and Gray regression analysis. Lost earnings were estimated using Bureau of Labor Statistics data. Measurements and main results: Of 922 consenting survivors, 386 (42%) were employed before ARDS (56% male; mean ± SD age, 45 ± 13 yr), with seven dying by 12-month follow-up. Of 379 previously employed 12-month survivors, 166 (44%) were jobless at 12-month follow-up. Accounting for competing risks of death and retirement, half of enrolled and previously employed survivors returned to work by 13 weeks after hospital discharge, with 68% ever returning by 12 months. Delays in return to work were associated with longer hospitalization and older age among nonwhite survivors. Over 12-month follow-up, 274 (71%) survivors accrued lost earnings, averaging $26,949 ± $22,447 (60% of pre-ARDS annual earnings). Jobless survivors experienced a 14% (95% confidence interval, 5-22%; P = 0.002) absolute decrease in private health insurance (from 44% pre-ARDS) and a 16% (95% confidence interval, 7-24%; P < 0.001) absolute increase in Medicare and Medicaid (from 33%). Conclusions: At 12 months after ARDS, nearly one-half of previously employed survivors were jobless. Post-ARDS joblessness is associated with readily identifiable patient and hospital variables and accompanied by substantial lost earnings and a shift toward government-funded healthcare coverage.

American journal of respiratory and critical care medicine · cohort or longitudinal · 124 citationsread the source →

A meta-ethnography of how children and young people with chronic non-cancer pain and their families experience and understand their condition, pain services, and treatments.

Background: Chronic non-cancer pain in childhood is widespread, affecting 20% to 35% of children and young people worldwide. For a sizeable number of children, chronic non-cancer pain has considerable negative impacts on their lives and quality of life, and leads to increased use of healthcare services and medication. In many countries, there are few services for managing children's chronic non-cancer pain, with many services being inadequate. Fourteen Cochrane Reviews assessing the effects of pharmacological, psychological, psychosocial, dietary or physical activity interventions for managing children's chronic non-cancer pain identified a lack of high-quality evidence to inform pain management. To design and deliver services and interventions that meet the needs of patients and their families, we need to understand how children with chronic non-cancer pain and their families experience pain, their views of services and treatments for chronic pain, and which outcomes are important to them. Objectives: 1. To synthesise qualitative studies that examine the experiences and perceptions of children with chronic non-cancer pain and their families regarding chronic non-cancer pain, treatments and services to inform the design and delivery of health and social care services, interventions and future research. 2. To explore whether our review findings help to explain the results of Cochrane Reviews of intervention effects of treatments for children's chronic non-cancer pain. 3. To determine if programme theories and outcomes of interventions match children and their families' views of desired treatments and outcomes. 4. To use our findings to inform the selection and design of patient-reported outcome measures for use in chronic non-cancer pain studies and interventions and care provision to children and their families. The review questions are: 1. How do children with chronic non-cancer pain and their families conceptualise chronic pain? 2. How do children with chronic non-cancer pain and their families live with chronic pain? 3. What do children with chronic non-cancer pain and their families think of how health and social care services respond to and manage their child's chronic pain? 4. What do children with chronic non-cancer pain and their families conceptualise as 'good' chronic pain management and what do they want to achieve from chronic pain management interventions and services? Search methods: Review strategy: we comprehensively searched 12 bibliographic databases including MEDLINE, CINAHL, PsycInfo and grey literature sources, and conducted supplementary searches in 2020. We updated the database searches in September 2022. Selection criteria: To identify published and unpublished qualitative research with children aged 3 months to 18 years with chronic non-cancer pain and their families focusing on their perceptions, experiences and views of chronic pain, services and treatments. The final inclusion criteria were agreed with a patient and public involvement group of children and young people with chronic non-cancer pain and their families. Data collection and analysis: We conducted a qualitative evidence synthesis using meta-ethnography, a seven-phase, systematic, interpretive, inductive methodology that takes into account the contexts and meanings of the original studies. We assessed the richness of eligible studies and purposively sampled rich studies ensuring they addressed the review questions. Cochrane Qualitative Methods Implementation Group guidance guided sampling. We assessed the methodological limitations of studies using the Critical Appraisal Skills Programme tool. We extracted data on study aims, focus, characteristics and conceptual findings from study reports using NVivo software. We compared these study data to determine how the studies related to one another and grouped studies by pain conditions for synthesis. We used meta-ethnography to synthesise each group of studies separately before synthesising them all together. Analysis and interpretation of studies involved children with chronic non-cancer pain and their families and has resulted in theory to inform service design and delivery. Sampling, organising studies for synthesis, and analysis and interpretation involved our patient and public involvement group who contributed throughout the conduct of the review. We used the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach to assess our confidence in each review finding. We used a matrix approach to integrate our findings with existing Cochrane Reviews on treatment effectiveness for children's chronic non-cancer pain. Main results: We synthesised 43 studies sampled from 170 eligible studies reported in 182 publications. Included studies involved 633 participants. GRADE-CERQual assessments of findings were mostly high (n = 21, 58%) or moderate (n = 12, 33%) confidence with three (8%) low or very low confidence. Poorly managed, moderate or severe chronic non-cancer pain had profound adverse impacts on family dynamics and relationships; family members' emotions, well-being, autonomy and sense of self-identity; parenting strategies; friendships and socialising; children's education and future employment prospects; and parental employment. Most children and parents understood chronic non-cancer pain as having an underlying biological cause and wanted curative treatment. However, families had difficulties seeking and obtaining support from health services to manage their child's pain and its impacts. Children and parents felt that healthcare professionals did not always listen to their experiences and expertise, or believe the child's pain. Some families repeatedly visited health services seeking a diagnosis and cure. Over time, some children and families gave up hope of effective treatment. Outcomes measured within trials and Cochrane Reviews of intervention effects did not include some outcomes of importance to children and families, including impacts of pain on the whole family and absence of pain. Cochrane Reviews have mainly neglected a holistic biopsychosocial approach, which specifies the interrelatedness of biological, psychological and social aspects of illness, when selecting outcome measures and considering how chronic pain management interventions work. Authors' conclusions: We had high or moderate confidence in the evidence contributing to most review findings. Further research, especially into families' experiences of treatments and services, could strengthen the evidence for low or very low confidence findings. Future research should also explore families' experiences in low- to middle-income contexts; of pain treatments including opioid use in children, which remains controversial; and of social care services. We need development and testing of family-centred interventions and services acceptable to families. Future trials of children's chronic non-cancer pain interventions should include family-centred outcomes.

The Cochrane database of systematic reviews · review · 16 citationsread the source →

Compensatory mechanisms activated with intermittent energy restriction: A randomized control trial.

Background & aims: Strong compensatory responses, with reduced resting metabolic rate (RMR), increased exercise efficiency (ExEff) and appetite, are activated when weight loss (WL) is achieved with continuous energy restriction (CER), which try to restore energy balance. Intermittent energy restriction (IER), where short spells of energy restriction are interspaced by periods of habitual energy intake, may offer some protection in minimizing those responses. We aimed to compare the effect of IER versus CER on body composition and the compensatory responses induced by WL. Methods: 35 adults (age: 39 ± 9 y) with obesity (BMI: 36 ± 4 kg/m2) were randomized to lose a similar weight with an IER (N = 18) or a CER (N = 17) diet over a 12 week period. Macronutrient composition and overall energy restriction (33% reduction) were similar between groups. Body weight/composition, RMR, fasting respiratory quotient (RQ), ExEff (10, 25, and 50 W), subjective appetite ratings (hunger, fullness, desire to eat, and prospective food consumption (PFC)), and appetite-regulating hormones (active ghrelin (AG), cholecystokinin (CCK), total peptide YY (PYY), active glucagon-like peptide-1 (GLP-1), and insulin) were measured before and after WL. Results: Changes in body weight (≈12.5% WL) and composition were similar in both groups. Fasting RQ and ExEff at 10 W increased in both groups. Losing weight, either by IER or CER dieting, did not induce significant changes in subjective appetite ratings. RMR decreased and ExEff at 25 and 50 W increased (P < 0.001 for all) in IER group only. Basal and postprandial AG increased (P < 0.05) in IER group, whereas basal active GLP-1 decreased (P = 0.033) in CER group only. Postprandial CCK decreased in both groups (P = 0.0012 and P = 0.009 for IER and CER groups, respectively). No between group differences were apparent for any of the outcomes. Conclusions: The technique used to achieve energy restriction, whether it is continuous or intermittent, does not appear to modulate the compensatory mechanisms activated by weight loss. Clinical trial registration number: NCT02169778 (the study was registered in clinicaltrial.gov).

Clinical nutrition (Edinburgh, Scotland) · randomised controlled trial · 77 citationsread the source →

Intermittent Hypoxia/Hyperoxia Versus Intermittent Hypoxia/Normoxia: Comparative Study in Prediabetes.

Background: Intermittent hypoxia/normoxia training (IHT) is considered a possible means to alleviate chronic diseases such as diabetes. In the last decade, another method of intermittent hypoxia/hyperoxia training (IHHT) began to enter the clinical practice, when the periods of breathing with atmospheric air are replaced by breathing a hyperoxic mixture. The present study compared the impact of adaptation to IHHT versus IHT on some metabolic variables in prediabetic patients. Methods: A placebo-controlled trial included 55 patients with prediabetes, sea level residents, ages 51-74 years. Control Group (16 patients) took sham 3-week course, and the IHHT Group (17 patients) and IHT Group (22 patients) received similar actual sessions of IHHT or IHT five times a week for 3 weeks, each session consisting four cycles of 5 minutes of hypoxia (12% O2) followed by 3 minutes of hyperoxia (IHHT, 33% O2) or 5 minutes of normoxia (IHT, breathing room air). Fasting glucose, oral glucose tolerance test (OGTT), blood lipids, and the level of blood oxygen saturation (SpO2) were investigated at baseline, as well as 1 day and 1 month after IHHT/IHT termination. Results: The study showed the same positive effect of two types of training: equal reduction of serum glucose concentrations, both fasting and 2 hours of OGTT; decreased total blood cholesterol and low-density lipoproteins; and an equally smaller drop in SpO2 during acute hypoxic test (breathing with 12% O2 for 20 minutes). Improved parameters persisted 1 month after training termination in both groups. Conclusion: One of the advantages of IHHT over IHT observed in this study could be some reduction in the duration of the sessions due to shortening reoxygenation periods. Further studies are required to search for additional beneficial effects of IHHT when using other training modes or other pathologies.

High altitude medicine & biology · randomised controlled trial · 26 citationsread the source →

Perspectives on HIV pre-exposure prophylaxis (PrEP) utilization and related intervention needs among people who inject drugs.

Background: Antiretroviral pre-exposure prophylaxis (PrEP) is clinically efficacious and recommended for HIV prevention among people who inject drugs (PWID), but uptake remains low and intervention needs are understudied. To inform the development of PrEP interventions for PWID, we conducted a qualitative study in the Northeastern USA, a region where recent clusters of new HIV infections have been attributed to injection drug use. Methods: We conducted qualitative interviews with 33 HIV-uninfected PWID (hereafter, "participants") and 12 clinical and social service providers (professional "key informants") in Boston, MA, and Providence, RI, in 2017. Trained interviewers used semi-structured interviews to explore PrEP acceptability and perceived barriers to use. Thematic analysis of coded data identified multilevel barriers to PrEP use among PWID and related intervention strategies. Results: Among PWID participants (n = 33, 55% male), interest in PrEP was high, but both participants and professional key informants (n = 12) described barriers to PrEP utilization that occurred at one or more socioecological levels. Individual-level barriers included low PrEP knowledge and limited HIV risk perception, concerns about PrEP side effects, and competing health priorities and needs due to drug use and dependence. Interpersonal-level barriers included negative experiences with healthcare providers and HIV-related stigma within social networks. Clinical barriers included poor infrastructure and capacity for PrEP delivery to PWID, and structural barriers related to homelessness, criminal justice system involvement, and lack of money or identification to get prescriptions. Participants and key informants provided some suggestions for strategies to address these multilevel barriers and better facilitate PrEP delivery to PWID. Conclusions: In addition to some of the facilitators of PrEP use identified by participants and key informants, we drew on our key findings and behavioral change theory to propose additional intervention targets. In particular, to help address the multilevel barriers to PrEP uptake and adherence, we discuss ways that interventions could target information, self-regulation and self-efficacy, social support, and environmental change. PrEP is clinically efficacious and has been recommended for PWID; thus, development and testing of strategies to improve PrEP delivery to this high-risk and socially marginalized population are needed.

Harm reduction journal · cohort or longitudinal · 119 citationsread the source →

Assessment of anticipatory grief in informal caregivers of dependants with dementia: a systematic review.

Objectives: Informal caregivers of dependants with dementia commence their bereavement experience long before the physical death of their dependant, a process referred to as "anticipatory grief". This represents an ambiguous state that has been acknowledged as a measurable variable among informal caregivers. The use of assessment tools for the identification of anticipatory grief is important for timely intervention to promote well-being and positive bereavement experiences. The aim of this systematic review is to identify and examine existing tools for assessing anticipatory grief among caregivers of dependants with dementia. Methods: MEDLINE, EMBASE, PsychINFO, CINAHL and Web of Science were searched to July 2021. Studies focusing on the development/evaluation of instruments for measuring anticipatory grief in dementia caregivers were eligible. The quality of each measurement was graded as positive, fair, poor or no information based on defined criteria. Results: 100 studies were identified. 33 papers were selected for full-text assessment and 12 papers met the eligibility criteria. Seven assessment tools were identified for measurement of pre-death grief caregivers - the Anticipatory Grief Scale (AGS), Marwit-Meuser Caregiver Grief Inventory (MM-CGI), MM-CGI-short-form (MM-CGI-SF), MM-CGI-brief (MM-CGI-BF), Prolonged Grief Scale (PG-12), Caregiver Grief Scale (CGS) and Caregiver Grief Questionnaire (CGQ). Based on content/construct validity, internal consistency and test-retest reliability the MM-CGI/MM-CGI-SF scored highest for quality followed by the CGS. Conclusion: Anticipatory grief in dementia has multiple facets that can be measured using self-scoring questionnaires. Our findings provide support for different measures of anticipatory grief. Further research is needed for the evaluation of the responsiveness and interpretability of these instruments.

Aging & mental health · systematic review · 22 citationsread the source →

Targeting risk factors for type 2 diabetes in American Indian youth: the Tribal Turning Point pilot study.

Background: American Indian (AI) youth are at high risk for type 2 diabetes. Objectives: To partner with Eastern Band of Cherokee Indians and Navajo Nation to develop a culturally sensitive behavioural intervention for youth (Tribal Turning Point; TTP) and assess feasibility in an 8-month randomized pilot study. Methods: We enrolled 62 overweight/obese AI children (7-10 years) who participated with ≥1 parent/primary caregiver. Intervention participants (n = 29) attended 12 group classes and five individual sessions. Control participants (n = 33) attended three health and safety group sessions. We analysed group differences for changes in anthropometrics (BMI, BMI z-score, waist circumference), cardiometabolic (insulin, glucose, blood pressure) and behavioural (physical activity and dietary self-efficacy) outcomes. Results: Study retention was 97%, and intervention group attendance averaged 84%. We observed significant treatment effects (p = 0.02) for BMI and BMI z-score: BMI increased in control (+1.0 kg m-2 , p < 0.001) but not intervention participants (+0.3 kg m-2 , p = 0.13); BMI z-score decreased in intervention (-0.17, p = 0.004) but not control participants (0.01, p = 0.82). There were no treatment effects for cardiometabolic or behavioural outcomes. Conclusions: We demonstrated that a behavioural intervention is feasible to deliver and improved obesity measures in AI youth. Future work should evaluate TTP for effectiveness, sustainability and long-term impact in expanded tribal settings.

Pediatric obesity · randomised controlled trial · 32 citationsread the source →

Third-wave cognitive behaviour therapies for weight management: A systematic review and network meta-analysis.

This systematic review and network meta-analysis synthesized evidence on the effects of third-wave cognitive behaviour therapies (3wCBT) on body weight, and psychological and physical health outcomes in adults with overweight or obesity. Studies that included a 3wCBT for the purposes of weight management and measured weight or body mass index (BMI) pre-intervention and ≥ 3 months post-baseline were identified through database searches (MEDLINE, CINAHL, Embase, Cochrane database [CENTRAL], PsycINFO, AMED, ASSIA, and Web of Science). Thirty-seven studies were eligible; 21 were randomized controlled trials (RCT) and included in the network meta-analyses. Risk of bias was assessed using RoB2, and evidence quality was assessed using GRADE. Random-effects pairwise meta-analysis found moderate- to high-quality evidence suggesting that 3wCBT had greater weight loss than standard behavioural treatment (SBT) at post-intervention (standardized mean difference [SMD]: -0.09, 95% confidence interval [CI]: -0.22, 0.04; N = 19; I2 = 32%), 12 months (SMD: -0.17, 95% CI: -0.36, 0.02; N = 5; I2 = 33%), and 24 months (SMD: -0.21, 95% CI: -0.42, 0.00; N = 2; I2 = 0%). Network meta-analysis compared the relative effectiveness of different types of 3wCBT that were not tested in head-to-head trials up to 18 months. Acceptance and commitment therapy (ACT)-based interventions had the most consistent evidence of effectiveness. Only ACT had RCT evidence of effectiveness beyond 18 months. Meta-regression did not identify any specific intervention characteristics (dose, duration, delivery) that were associated with greater weight loss. Evidence supports the use of 3wCBT for weight management, specifically ACT. Larger trials with long-term follow-up are needed to identify who these interventions work for, their most effective components, and the most cost-effective method of delivery.

Obesity reviews : an official journal of the International Association for the Study of Obesity · systematic review · 72 citationsread the source →

Working out the worries: A randomized controlled trial of high intensity interval training in generalized anxiety disorder.

Background: Aerobic exercise (AE) demonstrated an overall medium treatment effect in anxiety disorders (AD) but there is evidence for an "intensity-response" relationship. High intensity interval training (HIIT) was highly effective on a range of (mental) health parameters. However, so far no randomised-controlled trial (RCT) investigated the efficacy of HIIT in AD. Methods: 33 patients with generalized anxiety disorder (GAD) were randomly assigned to 12-day HIIT or a training of lower intensity (LIT). Anxiety, comorbid depression, stress-related bodily symptoms and perceived control over anxiety related stimuli (PC) were assessed at baseline, post-training and 30 days after baseline by using the Penn State Worry Questionnaire (PSWQ), the Hamilton Inventories for Anxiety and Depression (Ham-A, Ham-D), the Screening for Somatoform Symptoms-7 (SOMS-7) and the Anxiety Control Questionnaire (ACQ-R). Results: Both interventions showed moderate or large effects on all clinical measures. However, effects for HIIT were generally about twice as high as for LIT. PC negatively correlated with GAD severity in the whole sample at baseline but an association of training-induced changes in PC and worrying were exclusively detectable in HIIT. Conclusion: HIIT was highly effective and fast acting in GAD. Therefore, it may complement first-line treatment approaches in this condition.

Journal of anxiety disorders · randomised controlled trial · 27 citationsread the source →

Cognitive training for people with mild to moderate dementia.

Background: Cognitive impairment, a defining feature of dementia, plays an important role in the compromised functional independence that characterises the condition. Cognitive training (CT) is an approach that uses guided practice on structured tasks with the direct aim of improving or maintaining cognitive abilities. Objectives: • To assess effects of CT on cognitive and non-cognitive outcomes for people with mild to moderate dementia and their caregivers.• To compare effects of CT with those of other non-pharmacological interventions, including cognitive stimulation or rehabilitation, for people with mild to moderate dementia and their caregivers.• To identify and explore factors related to intervention and trial design that may be associated with the efficacy of CT for people with mild to moderate dementia and their caregivers. Search methods: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialised Register, on 5 July 2018. ALOIS contains records of clinical trials identified through monthly searches of several major healthcare databases and numerous trial registries and grey literature sources. In addition to this, we searched MEDLINE, Embase, PsycINFO, CINAHL, LILACS, Web of Science Core Collection, ClinicalTrials.gov, and the World Health Organization's trials portal, ICTRP, to ensure that searches were comprehensive and up-to-date. Selection criteria: We included randomised controlled trials (RCTs) that described interventions for people with mild to moderate dementia and compared CT versus a control or alternative intervention. Data collection and analysis: We extracted relevant data from published manuscripts and through contact with trial authors if required. We assessed risk of bias using the Cochrane 'Risk of bias' tool. We divided comparison conditions into active or passive control conditions and alternative treatments. We used a large number of measures and data to evaluate 19 outcomes at end of treatment, as well as 16 outcomes at follow-up in the medium term; we pooled this information in meta-analyses. We calculated pooled estimates of treatment effect using a random-effects model, and we estimated statistical heterogeneity using a standard Chi² statistic. We graded the evidence using GradePro. Main results: The 33 included trials were published between 1988 and 2018 and were conducted in 12 countries; most were unregistered, parallel-group, single-site RCTs, with samples ranging from 12 to 653 participants. Interventions were between two and 104 weeks long. We classified most experimental interventions as 'straight CT', but we classified some as 'augmented CT', and about two-thirds as multi-domain interventions. Researchers investigated 18 passive and 13 active control conditions, along with 15 alternative treatment conditions, including occupational therapy, mindfulness, reminiscence therapy, and others. The methodological quality of studies varied, but we rated nearly all studies as having high or unclear risk of selection bias due to lack of allocation concealment, and high or unclear risk of performance bias due to lack of blinding of participants and personnel. We used data from 32 studies in the meta-analysis of at least one outcome. Relative to a control condition, we found moderate-quality evidence showing a small to moderate effect of CT on our first primary outcome, composite measure of global cognition at end of treatment (standardised mean difference (SMD) 0.42, 95% confidence interval (CI) 0.23 to 0.62), and high-quality evidence showing a moderate effect on the secondary outcome of verbal semantic fluency (SMD 0.52, 95% CI 0.23 to 0.81) at end of treatment, with these gains retained in the medium term (3 to 12 months post treatment). In relation to many other outcomes, including our second primary outcome of clinical disease severity in the medium term, the quality of evidence was very low, so we were unable to determine whether CT was associated with any meaningful gains. When compared with an alternative treatment, we found that CT may have little to no effect on our first primary outcome of global cognition at end of treatment (SMD 0.21, 95% CI -0.23 to 0.64), but the quality of evidence was low. No evidence was available to assess our second primary outcome of clinical disease severity in the medium term. We found moderate-quality evidence showing that CT was associated with improved mood of the caregiver at end of treatment, but this was based on a single trial. The quality of evidence in relation to many other outcomes at end of treatment and in the medium term was too low for us to determine whether CT was associated with any gains, but we are moderately confident that CT did not lead to any gains in mood, behavioural and psychological symptoms, or capacity to perform activities of daily living. Authors' conclusions: Relative to a control intervention, but not to a variety of alternative treatments, CT is probably associated with small to moderate positive effects on global cognition and verbal semantic fluency at end of treatment, and these benefits appear to be maintained in the medium term. Our certainty in relation to many of these findings is low or very low. Future studies should take stronger measures to mitigate well-established risks of bias, and should provide long-term follow-up to improve our understanding of the extent to which observed gains are retained. Future trials should also focus on direct comparison of CT versus alternative treatments rather than passive or active control conditions.

The Cochrane database of systematic reviews · meta-analysis · 183 citationsread the source →

Cost-effectiveness of adherence-enhancing interventions: a quality assessment of the evidence.

Objective: To determine whether the current cost-effectiveness evidence on adherence-enhancing interventions (AEIs) was of sufficient quality to aid in decision-making regarding medication adherence policies. Data sources: A computerized search of Embase, MEDLINE, Cinahl, Econlit, NHSEED, Psychlit, EPIC, and Cochrane databases (1980-April 2004) was performed. English-language human subject articles were identified using the key words compliance, adherence, concordance, patient assistance, therapeutic alliance, costs, economics, efficiency, resource use/utilization, cost-of-illness, cost-effectiveness, cost-minimization, cost-utility, and cost-benefit. Study selection and data extraction: Studies that appeared to assess the cost-effectiveness of medication AEIs were included. Methodologic rigor was assessed using 15 minimum quality criteria. Data synthesis: We found 45 comparative studies in 43 publications. Asthma (14 studies) and psychiatric illness (12 studies) were most commonly investigated. In 33 studies, interventions were educational, 18 had multiple components, and 23 did not appear to be linked to proven reasons for nonadherence. Reporting of adherence and outcome results was often unclear. Cost data were poorer quality than outcome data, using average or estimated costs and omitting some cost elements. Nine studies carried out incremental economic analysis. No study met all quality criteria. Conclusions: We were not able to make definitive conclusions about the cost-effectiveness of AEIs due to the heterogeneity of the studies found and incomplete reporting of results. Important policy decisions need to be made about nonadherence; however, they are currently being made in a vacuum of adequate information. AEIs must be based on reasons for nonadherence and be evaluated using accepted clinical and economic quality criteria.

The Annals of pharmacotherapy · review · 52 citationsread the source →

A Preliminary, Randomized-Controlled Trial of Mindfulness and Game-Based Executive Function Trainings to Promote Self-Regulation in Internationally-Adopted Children.

Although many children adopted internationally show remarkable recovery once placed in families, as a group they continue to exhibit persisting developmental deficits and delays in self-regulation. The current study uses a stratified, randomized, controlled trial to evaluate the effects of mindfulness-based and executive function trainings (EFTs) on internationally adopted (IA) children's self-regulation, including effortful/inhibitory control, attention, delay of gratification, and emotion-regulation. IA children ages 6-10 years were randomized into mindfulness training (MT), EFT, or no intervention (NI) groups. The MT and EFT groups attended 12 one-hour group sessions. Ninety-six children (MT, n = 33; EFT, n = 32; NI, n = 31) completed the study and were tested on computerized and non-computerized measures of self-regulation. Compared with the NI group, the MT group improved delay of gratification, and the EFT group improved inhibitory control and selective attention. There was no effect of either intervention on emotion regulation. MTs and EFTs show promise for improving self-regulation in IA children.

Development and psychopathology · randomised controlled trial · 14 citationsread the source →

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 →

Helping Yourself by Offering Help: Mediators of Expressive Helping in Survivors of Hematopoietic Stem Cell Transplant.

Background: A randomized experiment by Rini et al. (Health Psychol. 33(12):1541-1551, 2014) demonstrated that expressive helping, which involves three expressive writing sessions regarding hematopoietic stem cell transplant, followed by one writing session directed toward helping other stem cell transplant recipients, reduced psychological distress and bothersome physical symptoms among stem cell transplant recipients with elevated survivorship problems, relative to a neutral writing control condition. Purpose: The current study evaluated whether word use reflective of emotional expression, cognitive processing, and change in perspective mediates the effects of expressive helping. Method: The essays of 67 stem cell transplant recipients with high survivorship problems were analyzed with Linguistic Inquiry and Word Count. Multiple mediation modeling was used to test the hypothesized mechanisms of expressive helping on distress and bothersome physical symptoms. Results: Relative to the control condition, expressive helping produced significant reductions in psychological distress and marginal reductions in physical symptom bother in the analyzed subset of participants from the parent study. Results indicated that positive emotion word use significantly mediated effects of expressive helping on reduced distress, but only for participants who used average (compared to above or below average) rates of negative emotion words. Cognitive processing and change in perspective did not significantly mediate benefits of expressive helping. Conclusions: Expressive helping carried its positive effects on distress through participants' higher expression of positive emotions when coupled with moderate rates of negative emotions. Findings highlight the benefit of expressing both positive and negative emotions in stressful situations.

Annals of behavioral medicine : a publication of the Society of Behavioral Medicine · 7 citationsread the source →

The psychiatric sequelae of the COVID-19 pandemic in adolescents, adults, and health care workers.

Background: The COVID-19 pandemic is the most serious global public health crisis since the 1918 influenza pandemic. This study is the first to assess its mental health impact across the lifespan in the United States in adolescents, adults, and health care workers. Methods: We recruited 4909 participants through an online survey advertising on Facebook and Instagram to assess exposure to COVID-19 and psychiatric symptoms from April 27 to July 13. We also recruited through the University of Pittsburgh, University of Pittsburgh Medical Center, and other health care systems around Pittsburgh. The primary outcomes were clinically significant depression, anxiety, and posttraumatic stress disorder (PTSD) symptoms, suicidal ideation or behavior, and grief reactions since COVID-19. Results: Adolescents were significantly more likely to report moderate to severe symptoms of depression (55% vs. 29%; χ2  = 122, df = 1; p < .001), anxiety (48% vs. 29%; χ2  = 73; df = 1; p < .001), PTSD (45% vs. 33%; χ2  = 12; df = 1; p < .001), suicidal ideation or behavior (38% vs. 16%; χ2  = 117; df = 1; p < .001), and sleep problems (69% vs. 57%; χ2  = 26; df = 1; p < .001) compared to adults. The rates of intense grief reactions among those who lost someone to COVID-19 was 55%. Loneliness was the most common predictor across outcomes and higher number of hours spent on social media and exposure to media about COVID-19 predicted depression symptoms and suicidal ideation or behavior in adolescents. Conclusions: The COVID-19 pandemic is associated with increased rates of clinically significant psychiatric symptoms. Loneliness could put individuals at increased risk for the onset of psychiatric disorders.

Depression and anxiety · 157 citationsread the source →

Evaluation of a collaborative care model for integrated primary care of common mental disorders comorbid with chronic conditions in South Africa.

Background: The rise in multimorbid chronic conditions in South Africa, large treatment gap for common mental disorders (CMDs) and shortage of mental health specialists demands a task sharing approach to chronic disease management that includes treatment for co-existing CMDs to improve health outcomes. The aim of this study was thus to evaluate a task shared integrated collaborative care package of care for chronic patients with co-existing depressive and alcohol use disorder (AUD) symptoms. Methods: The complex intervention strengthened capacity of primary care nurse practitioners to identify, diagnose and review symptoms of CMDs among chronic care patients; and implemented a stepped up referral system, that included clinic-based psychosocial lay counsellors, doctors and mental health specialists. Under real world conditions, in four PHC facilities, a repeat cross-sectional Facility Detection Survey (FDS) assessed changes in capacity of nurses to correctly detect CMDs in 1310 patients before implementation and 1246 patients following implementation of the intervention at 12 months; and a non-randomly assigned comparison group cohort study comprising 373 screen positive patients with depressive symptoms using the Patient Health Questionnaire-9 (PHQ9) at baseline, evaluated responses of patients correctly identified and referred for treatment (intervention arm) or not identified and referred (control arm) at three and 12 months. Results: The FDS showed a significant increase in the identification of depression and AUD from pre-implementation to 12-month post-implementation. Depression: (5.8 to 16.4%) 95% CI [2.9, 19.1]); AUD: (0 to 13.8%) 95% CI [0.6-24.9]. In the comparison group cohort study, patients with depressive symptoms having more than a 50% reduction in PHQ-9 scores were greater in the treatment group (n = 69, 55.2%) compared to the comparison group (n = 49, 23.4%) at 3 months (RR = 2.10, p < 0.001); and 12 months follow-up (intervention: n = 57, 47.9%; comparison: n = 60, 30.8%; RR = 1.52, p = 0.006). Remission (PHQ-9 ≤ 5) was greater in the intervention group (n = 32, 26.9%) than comparison group (n = 33, 16.9%) at 12 months (RR = 1.72, p = 0.016). Conclusion: A task shared collaborative stepped care model can improve detection of CMDs and reduce depressive symptoms among patients with chronic conditions under real world conditions.

BMC psychiatry · 55 citationsread the source →

Determinants of breastfeeding initiation and cessation among employed mothers: a prospective cohort study.

Background: The U.S. continues to have one of the lowest breastfeeding rates in the industrialized world. Studies have shown that full-time employment and early return to work decreased breastfeeding duration, but little is known about the relationship between leave policies and breastfeeding initiation and cessation. This study aimed to identify workplace-related barriers and facilitators associated with breastfeeding initiation and cessation in the first 6 months postpartum. Methods: A prospective cohort study design was utilized to recruit 817 Minnesota women aged 18 and older while hospitalized for childbirth. Selection criteria included English-speaking, employed mothers with a healthy, singleton birth. These women were followed up using telephone interviews at 6 weeks, 12 weeks, and 6 months after childbirth. The main study outcomes were breastfeeding initiation, measured during hospital enrollment, and breastfeeding cessation by 6 months postpartum. Results: Women were 30 years old; 86 % were White, and 73 % were married. Breastfeeding rates were 81 % at childbirth, 67 % at 6 weeks, 49 % at 12 weeks, and 33 % at 6 months postpartum. Logistic regression revealed the odds of breastfeeding initiation were higher for women who: held professional jobs, were primiparae, had graduate degree, did not smoke prenatally, had no breastfeeding problems, and had family or friends who breastfeed. Survival analyses showed the hazard for breastfeeding cessation by 6 months was: higher for women who returned to work at any time during the 6 months postpartum versus those who did not return, lower for professional workers, higher among single than married women, higher for every educational category compared to graduate school, and higher for those with no family or friends who breastfeed. Conclusions: While employer paid leave policy did not affect breastfeeding initiation or cessation, women who took shorter leaves were more likely to stop breastfeeding in the first 6 months postpartum. Future research should examine women's awareness of employer policies regarding paid and unpaid leave.

BMC pregnancy and childbirth · 89 citationsread the source →

A double-blind, placebo-controlled pilot trial of quetiapine for the treatment of Type A and Type B alcoholism.

Background: Atypical antipsychotics may be useful in the treatment of alcohol dependence. Human trials suggest that atypical antipsychotics may reduce alcohol craving and consumption, especially among patients with comorbid psychopathology. Therefore, these medications may be more useful for treating more severely affected alcoholics, such as patients with Type B alcoholism. Type B alcoholics are characterized by an early age of onset of problem drinking, high severity of alcohol dependence, increased psychopathology, and treatment-resistance. Quetiapine is an atypical antipsychotic with a favorable side effect profile, and may be a promising medication for the treatment of alcohol dependence, particularly Type B alcoholism. Methods: Male and female alcoholics (33 Type A and 28 Type B) were included in a 12-week, double-blind, placebo-controlled trial. After detoxification, patients were randomized to receive quetiapine (n = 29), 400 mg/d at bedtime, or placebo (n = 32). The primary outcome measure was the quantity and frequency of alcohol consumption, measured by the timeline follow back. Results: Forty-seven patients (77%) completed the trial, with no significant between-group differences in treatment retention. Nine quetiapine-treated patients (31%) maintained complete abstinence compared with 2 placebo-treated patients (6%) (chi(2) = 6.3, P = 0.012). There was a significant interaction between quetiapine and alcoholic subtype. As predicted, quetiapine- versus placebo-treated Type B alcoholics had significantly fewer days of drinking and fewer days of heavy drinking. Alcohol craving was also significantly reduced in quetiapine-treated compared with placebo-treated Type B alcoholics. Among Type A alcoholics, quetiapine provided no advantage over placebo in improving drinking outcomes. Conclusions: Quetiapine may be effective for the treatment of alcohol dependence, particularly in the more complicated Type B, early-onset alcoholics.

Journal of clinical psychopharmacology · randomised controlled trial · 59 citationsread the source →

Associations between adolescent adversity and young adult depression symptoms and allostatic load in Mexican-origin individuals.

Childhood adversity increases risk for depression and higher allostatic load (AL), defined as long-term wear and tear on the body, and adolescence is an especially sensitive time for adversity to be biologically embedded. Individuals of Mexican origin may face multiple forms of adversities relating to their intersectional identities of ethnicity and class, including ethnic discrimination and economic hardship, the experience of which may further depend on sex. However, relatively little research has simultaneously assessed associations between these two types of adolescent adversity and outcomes of both young adult depression and AL longitudinally in Mexican-origin individuals. This preregistered study addressed these gaps in a longitudinal study of 208 Mexican-origin participants. Ethnic discrimination and economic hardship were assessed annually from ages 10-19 and AL and depression symptoms were assessed at age 26. Sex differences were also tested. Perceived discrimination in adolescence significantly predicted higher levels of depression at age 26 (β =.09, p = .045, R2 =.03, ΔR2 = 0.005, 95% CI [.002,.181]). In addition, age 26 depression levels moderated the association between adolescent economic hardship and age 26 AL (β = -.17, p = .03, R2 =.12, ΔR2 =.028, 95% CI [-.33, -.02]). Participants exhibited higher AL with high levels of economic hardship but low levels of depression, as well as with low levels of economic hardship and high depression, suggesting that both psychological resilience to economic hardship and the association between mental health and AL may depend on context. Findings indicate intersectional effects of different types of adversity during adolescence on mental and physical health in young adulthood within Latino individuals.

Psychoneuroendocrinology · 1 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 →

Psychological therapies for the treatment of mental disorders in low- and middle-income countries affected by humanitarian crises.

Background: People living in humanitarian settings in low- and middle-income countries (LMICs) are exposed to a constellation of stressors that make them vulnerable to developing mental disorders. Mental disorders with a higher prevalence in these settings include post-traumatic stress disorder (PTSD) and major depressive, anxiety, somatoform (e.g. medically unexplained physical symptoms (MUPS)), and related disorders. A range of psychological therapies are used to manage symptoms of mental disorders in this population. Objectives: To compare the effectiveness and acceptability of psychological therapies versus control conditions (wait list, treatment as usual, attention placebo, psychological placebo, or no treatment) aimed at treating people with mental disorders (PTSD and major depressive, anxiety, somatoform, and related disorders) living in LMICs affected by humanitarian crises. Search methods: We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR), the Cochrane Central Register of Controlled Trials (Wiley), MEDLINE (OVID), Embase (OVID), and PsycINFO (OVID), with results incorporated from searches to 3 February 2016. We also searched the World Health Organization (WHO) trials portal (ICTRP) and ClinicalTrials.gov to identify any unpublished or ongoing studies. We checked the reference lists of relevant studies and reviews. Selection criteria: All randomised controlled trials (RCTs) comparing psychological therapies versus control conditions (including no treatment, usual care, wait list, attention placebo, and psychological placebo) to treat adults and children with mental disorders living in LMICs affected by humanitarian crises. Data collection and analysis: We used standard Cochrane procedures for collecting data and evaluating risk of bias. We calculated standardised mean differences for continuous outcomes and risk ratios for dichotomous data, using a random-effects model. We analysed data at endpoint (zero to four weeks after therapy); at medium term (one to four months after therapy); and at long term (six months or longer). GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) was used to assess the quality of evidence for post-traumatic stress disorder (PTSD), depression, anxiety and withdrawal outcomes. Main results: We included 36 studies (33 RCTs) with a total of 3523 participants. Included studies were conducted in sub-Saharan Africa, the Middle East and North Africa, and Asia. Studies were implemented in response to armed conflicts; disasters triggered by natural hazards; and other types of humanitarian crises. Together, the 33 RCTs compared eight psychological treatments against a control comparator. Four studies included children and adolescents between 5 and 18 years of age. Three studies included mixed populations (two studies included participants between 12 and 25 years of age, and one study included participants between 16 and 65 years of age). Remaining studies included adult populations (18 years of age or older).Included trials compared a psychological therapy versus a control intervention (wait list in most studies; no treatment; treatment as usual). Psychological therapies were categorised mainly as cognitive-behavioural therapy (CBT) in 23 comparisons (including seven comparisons focused on narrative exposure therapy (NET), two focused on common elements treatment approach (CETA), and one focused on brief behavioural activation treatment (BA)); eye movement desensitisation and reprocessing (EMDR) in two comparisons; interpersonal psychotherapy (IPT) in three comparisons; thought field therapy (TFT) in three comparisons; and trauma or general supportive counselling in two comparisons. Although interventions were described under these categories, several psychotherapeutic elements were common to a range of therapies (i.e. psychoeducation, coping skills).In adults, psychological therapies may substantially reduce endpoint PTSD symptoms compared to control conditions (standardised mean difference (SMD) -1.07, 95% confidence interval (CI) -1.34 to -0.79; 1272 participants; 16 studies; low-quality evidence). The effect is smaller at one to four months (SMD -0.49, 95% CI -0.68 to -0.31; 1660 participants; 18 studies) and at six months (SMD -0.37, 95% CI -0.61 to -0.14; 400 participants; five studies). Psychological therapies may also substantially reduce endpoint depression symptoms compared to control conditions (SMD -0.86, 95% CI -1.06 to -0.67; 1254 participants; 14 studies; low-quality evidence). Similar to PTSD symptoms, follow-up data at one to four months showed a smaller effect on depression (SMD -0.42, 95% CI -0.63 to -0.21; 1386 participants; 16 studies). Psychological therapies may moderately reduce anxiety at endpoint (SMD -0.74, 95% CI -0.98 to -0.49; 694 participants; five studies; low-quality evidence) and at one to four months' follow-up after treatment (SMD -0.53, 95% CI -0.66 to -0.39; 969 participants; seven studies). Dropout rates are probably similar between study conditions (19.5% with control versus 19.1% with psychological therapy (RR 0.98 95% CI 0.82 to 1.16; 2930 participants; 23 studies, moderate quality evidence)).In children and adolescents, we found very low quality evidence for lower endpoint PTSD symptoms scores in psychotherapy conditions (CBT) compared to control conditions, although the confidence interval is wide (SMD -1.56, 95% CI -3.13 to 0.01; 130 participants; three studies;). No RCTs provided data on major depression or anxiety in children. The effect on withdrawal was uncertain (RR 1.87 95% CI 0.47 to 7.47; 138 participants; 3 studies, low quality evidence).We did not identify any studies that evaluated psychological treatments on (symptoms of) somatoform disorders or MUPS in LMIC humanitarian settings. Authors' conclusions: There is low quality evidence that psychological therapies have large or moderate effects in reducing PTSD, depressive, and anxiety symptoms in adults living in humanitarian settings in LMICs. By one to four month and six month follow-up assessments treatment effects were smaller. Fewer trials were focused on children and adolescents and they provide very low quality evidence of a beneficial effect of psychological therapies in reducing PTSD symptoms at endpoint. Confidence in these findings is influenced by the risk of bias in the studies and by substantial levels of heterogeneity. More research evidence is needed, particularly for children and adolescents over longer periods of follow-up.

The Cochrane database of systematic reviews · meta-analysis · 114 citationsread the source →

Psychological therapies for women who experience intimate partner violence.

Background: Intimate partner violence (IPV) against women is prevalent and strongly associated with mental health problems. Women experiencing IPV attend health services frequently for mental health problems. The World Health Organization recommends that women who have experienced IPV and have a mental health diagnosis should receive evidence-based mental health treatments. However, it is not known if psychological therapies work for women in the context of IPV and whether they cause harm. Objectives: To assess the effectiveness of psychological therapies for women who experience IPV on the primary outcomes of depression, self-efficacy and an indicator of harm (dropouts) at six- to 12-months' follow-up, and on secondary outcomes of other mental health symptoms, anxiety, quality of life, re-exposure to IPV, safety planning and behaviours, use of healthcare and IPV services, and social support. Search methods: We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR), CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, and three other databases, to the end of October 2019. We also searched international trials registries to identify unpublished or ongoing trials and handsearched selected journals, reference lists of included trials and grey literature. Selection criteria: We included randomised controlled trials (RCTs), quasi-RCTs, cluster-RCTs and cross-over trials of psychological therapies with women aged 16 years and older who self-reported recent or lifetime experience of IPV. We included trials if women also experienced co-existing mental health diagnoses or substance abuse issues, or both. Psychological therapies included a wide range of interventions that targeted cognition, motivation and behaviour compared with usual care, no treatment, delayed or minimal interventions. We classified psychological therapies according to Cochrane Common Mental Disorders's psychological therapies list. Data collection and analysis: Two review authors extracted data and undertook 'Risk of Bias' assessment. Treatment effects were compared between experimental and comparator interventions at short-term (up to six months post-baseline), medium-term (six to under 12 months, primary outcome time point), and long-term follow-up (12 months and above). We used standardised mean difference (SMD) for continuous and odds ratio (OR) for dichotomous outcomes, and used random-effects meta-analysis, due to high heterogeneity across trials. Main results: We included 33 psychological trials involving 5517 women randomly assigned to experimental (2798 women, 51%) and comparator interventions (2719 women, 49%). Psychological therapies included 11 integrative therapies, nine humanistic therapies, six cognitive behavioural therapy, four third-wave cognitive behavioural therapies and three other psychologically-orientated interventions. There were no trials classified as psychodynamic therapies. Most trials were from high-income countries (19 in USA, three in Iran, two each in Australia and Greece, and one trial each in China, India, Kenya, Nigeria, Pakistan, Spain and UK), among women recruited from healthcare, community, shelter or refuge settings, or a combination of any or all of these. Psychological therapies were mostly delivered face-to-face (28 trials), but varied by length of treatment (two to 50 sessions) and staff delivering therapies (social workers, nurses, psychologists, community health workers, family doctors, researchers). The average sample size was 82 women (14 to 479), aged 37 years on average, and 66% were unemployed. Half of the women were married or living with a partner and just over half of the participants had experienced IPV in the last 12 months (17 trials), 6% in the past two years (two trials) and 42% during their lifetime (14 trials). Whilst 20 trials (61%) described reliable low-risk random-sampling strategies, only 12 trials (36%) described reliable procedures to conceal the allocation of participant status. While 19 trials measured women's depression, only four trials measured depression as a continuous outcome at medium-term follow-up. These showed a probable beneficial effect of psychological therapies in reducing depression (SMD -0.24, 95% CI -0.47 to -0.01; four trials, 600 women; moderate-certainty evidence). However, for self-efficacy, there may be no evidence of a difference between groups (SMD -0.12, 95% CI -0.33 to 0.09; one trial with medium-term follow-up data, 346 women; low-certainty evidence). Further, there may be no difference between the number of women who dropped out from the experimental or comparator intervention groups, an indicator of no harm (OR 1.04, 95% CI 0.75 to 1.44; five trials with medium-term follow-up data, 840 women; low-certainty evidence). Although no trials reported adverse events from psychological therapies or participation in the trial, only one trial measured harm outcomes using a validated scale. For secondary outcomes, trials measured anxiety only at short-term follow-up, showing that psychological therapies may reduce anxiety symptoms (SMD -0.96, 95% CI -1.29 to -0.63; four trials, 158 women; low-certainty evidence). However, within medium-term follow-up, low-certainty evidence revealed that there may be no evidence between groups for the outcomes safety planning (SMD 0.04, 95% CI -0.18 to 0.25; one trial, 337 women), post-traumatic stress disorder (SMD -0.24, 95% CI -0.54 to 0.06; four trials, 484 women) or re-exposure to any form of IPV (SMD 0.03, 95% CI -0.14 to 0.2; two trials, 547 women). Authors' conclusions: There is evidence that for women who experience IPV, psychological therapies probably reduce depression and may reduce anxiety. However, we are uncertain whether psychological therapies improve other outcomes (self-efficacy, post-traumatic stress disorder, re-exposure to IPV, safety planning) and there are limited data on harm. Thus, while psychological therapies probably improve emotional health, it is unclear if women's ongoing needs for safety, support and holistic healing from complex trauma are addressed by this approach. There is a need for more interventions focused on trauma approaches and more rigorous trials (with consistent outcomes at similar follow-up time points), as we were unable to synthesise much of the research.

The Cochrane database of systematic reviews · meta-analysis · 78 citationsread the source →

Psychological interventions for antisocial personality disorder.

Background: Antisocial personality disorder (AsPD) is associated with poor mental health, criminality, substance use and relationship difficulties. This review updates Gibbon 2010 (previous version of the review). Objectives: To evaluate the potential benefits and adverse effects of psychological interventions for adults with AsPD. Search methods: We searched CENTRAL, MEDLINE, Embase, 13 other databases and two trials registers up to 5 September 2019. We also searched reference lists and contacted study authors to identify studies. Selection criteria: Randomised controlled trials of adults, where participants with an AsPD or dissocial personality disorder diagnosis comprised at least 75% of the sample randomly allocated to receive a psychological intervention, treatment-as-usual (TAU), waiting list or no treatment. The primary outcomes were aggression, reconviction, global state/functioning, social functioning and adverse events. Data collection and analysis: We used standard methodological procedures expected by Cochrane. Main results: This review includes 19 studies (eight new to this update), comparing a psychological intervention against TAU (also called 'standard Maintenance'(SM) in some studies). Eight of the 18 psychological interventions reported data on our primary outcomes. Four studies focussed exclusively on participants with AsPD, and 15 on subgroups of participants with AsPD. Data were available from only 10 studies involving 605 participants. Eight studies were conducted in the UK and North America, and one each in Iran, Denmark and the Netherlands. Study duration ranged from 4 to 156 weeks (median = 26 weeks). Most participants (75%) were male; the mean age was 35.5 years. Eleven studies (58%) were funded by research councils. Risk of bias was high for 13% of criteria, unclear for 54% and low for 33%. Cognitive behaviour therapy (CBT) + TAU versus TAU One study (52 participants) found no evidence of a difference between CBT + TAU and TAU for physical aggression (odds ratio (OR) 0.92, 95% CI 0.28 to 3.07; low-certainty evidence) for outpatients at 12 months post-intervention. One study (39 participants) found no evidence of a difference between CBT + TAU and TAU for social functioning (mean difference (MD) -1.60 points, 95% CI -5.21 to 2.01; very low-certainty evidence), measured by the Social Functioning Questionnaire (SFQ; range = 0-24), for outpatients at 12 months post-intervention. Impulsive lifestyle counselling (ILC) + TAU versus TAU One study (118 participants) found no evidence of a difference between ILC + TAU and TAU for trait aggression (assessed with Buss-Perry Aggression Questionnaire-Short Form) for outpatients at nine months (MD 0.07, CI -0.35 to 0.49; very low-certainty evidence). One study (142 participants) found no evidence of a difference between ILC + TAU and TAU alone for the adverse event of death (OR 0.40, 95% CI 0.04 to 4.54; very low-certainty evidence) or incarceration (OR 0.70, 95% CI 0.27 to 1.86; very low-certainty evidence) for outpatients between three and nine months follow-up. Contingency management (CM) + SM versus SM One study (83 participants) found evidence that, compared to SM alone, CM + SM may improve social functioning measured by family/social scores on the Addiction Severity Index (ASI; range = 0 (no problems) to 1 (severe problems); MD -0.08, 95% CI -0.14 to -0.02; low-certainty evidence) for outpatients at six months. 'Driving whilst intoxicated' programme (DWI) + incarceration versus incarceration One study (52 participants) found no evidence of a difference between DWI + incarceration and incarceration alone on reconviction rates (hazard ratio 0.56, CI -0.19 to 1.31; very low-certainty evidence) for prisoner participants at 24 months. Schema therapy (ST) versus TAU One study (30 participants in a secure psychiatric hospital, 87% had AsPD diagnosis) found no evidence of a difference between ST and TAU for the number of participants who were reconvicted (OR 2.81, 95% CI 0.11 to 74.56, P = 0.54) at three years. The same study found that ST may be more likely to improve social functioning (assessed by the mean number of days until patients gain unsupervised leave (MD -137.33, 95% CI -271.31 to -3.35) compared to TAU, and no evidence of a difference between the groups for overall adverse events, classified as the number of people experiencing a global negative outcome over a three-year period (OR 0.42, 95% CI 0.08 to 2.19). The certainty of the evidence for all outcomes was very low. Social problem-solving (SPS) + psychoeducation (PE) versus TAU One study (17 participants) found no evidence of a difference between SPS + PE and TAU for participants' level of social functioning (MD -1.60 points, 95% CI -5.43 to 2.23; very low-certainty evidence) assessed with the SFQ at six months post-intervention. Dialectical behaviour therapy versus TAU One study (skewed data, 14 participants) provided very low-certainty, narrative evidence that DBT may reduce the number of self-harm days for outpatients at two months post-intervention compared to TAU. Psychosocial risk management (PSRM; 'Resettle') versus TAU One study (skewed data, 35 participants) found no evidence of a difference between PSRM and TAU for a number of officially recorded offences at one year after release from prison. It also found no evidence of difference between the PSRM and TAU for the adverse event of death during the study period (OR 0.89, 95% CI 0.05 to 14.83, P = 0.94, 72 participants (90% had AsPD), 1 study, very low-certainty evidence). Authors' conclusions: There is very limited evidence available on psychological interventions for adults with AsPD. Few interventions addressed the primary outcomes of this review and, of the eight that did, only three (CM + SM, ST and DBT) showed evidence that the intervention may be more effective than the control condition. No intervention reported compelling evidence of change in antisocial behaviour. Overall, the certainty of the evidence was low or very low, meaning that we have little confidence in the effect estimates reported. The conclusions of this update have not changed from those of the original review, despite the addition of eight new studies. This highlights the ongoing need for further methodologically rigorous studies to yield further data to guide the development and application of psychological interventions for AsPD and may suggest that a new approach is required.

The Cochrane database of systematic reviews · meta-analysis · 32 citationsread the source →

Bariatric surgery, lifestyle interventions and orlistat for severe obesity: the REBALANCE mixed-methods systematic review and economic evaluation.

Background: Adults with severe obesity [body mass index (BMI) of ≥ 35 kg/m2] have an increased risk of comorbidities and psychological, social and economic consequences. Objectives: Systematically review bariatric surgery, weight-management programmes (WMPs) and orlistat pharmacotherapy for adults with severe obesity, and evaluate the feasibility, acceptability, clinical effectiveness and cost-effectiveness of treatment. Data sources: Electronic databases including MEDLINE, EMBASE, PsycINFO, the Cochrane Central Register of Controlled Trials and the NHS Economic Evaluation Database were searched (last searched in May 2017). Review methods: Four systematic reviews evaluated clinical effectiveness, cost-effectiveness and qualitative evidence for adults with a BMI of ≥ 35 kg/m2. Data from meta-analyses populated a microsimulation model predicting costs, outcomes and cost-effectiveness of Roux-en-Y gastric bypass (RYGB) surgery and the most effective lifestyle WMPs over a 30-year time horizon from a NHS perspective, compared with current UK population obesity trends. Interventions were cost-effective if the additional cost of achieving a quality-adjusted life-year is < £20,000-30,000. Results: A total of 131 randomised controlled trials (RCTs), 26 UK studies, 33 qualitative studies and 46 cost-effectiveness studies were included. From RCTs, RYGB produced the greatest long-term weight change [-20.23 kg, 95% confidence interval (CI) -23.75 to -16.71 kg, at 60 months]. WMPs with very low-calorie diets (VLCDs) produced the greatest weight loss at 12 months compared with no WMPs. Adding a VLCD to a WMP gave an additional mean weight change of -4.41 kg (95% CI -5.93 to -2.88 kg) at 12 months. The intensive Look AHEAD WMP produced mean long-term weight loss of 6% in people with type 2 diabetes mellitus (at a median of 9.6 years). The microsimulation model found that WMPs were generally cost-effective compared with population obesity trends. Long-term WMP weight regain was very uncertain, apart from Look AHEAD. The addition of a VLCD to a WMP was not cost-effective compared with a WMP alone. RYGB was cost-effective compared with no surgery and WMPs, but the model did not replicate long-term cost savings found in previous studies. Qualitative data suggested that participants could be attracted to take part in WMPs through endorsement by their health-care provider or through perceiving innovative activities, with WMPs being delivered to groups. Features improving long-term weight loss included having group support, additional behavioural support, a physical activity programme to attend, a prescribed calorie diet or a calorie deficit. Limitations: Reviewed studies often lacked generalisability to UK settings in terms of participants and resources for implementation, and usually lacked long-term follow-up (particularly for complications for surgery), leading to unrealistic weight regain assumptions. The views of potential and actual users of services were rarely reported to contribute to service design. This study may have failed to identify unpublished UK evaluations. Dual, blinded numerical data extraction was not undertaken. Conclusions: Roux-en-Y gastric bypass was costly to deliver, but it was the most cost-effective intervention. Adding a VLCD to a WMP was not cost-effective compared with a WMP alone. Most WMPs were cost-effective compared with current population obesity trends. Future work: Improved reporting of WMPs is needed to allow replication, translation and further research. Qualitative research is needed with adults who are potential users of, or who fail to engage with or drop out from, WMPs. RCTs and economic evaluations in UK settings (e.g. Tier 3, commercial programmes or primary care) should evaluate VLCDs with long-term follow-up (≥ 5 years). Decision models should incorporate relevant costs, disease states and evidence-based weight regain assumptions. Study registration: This study is registered as PROSPERO CRD42016040190. Funding: The National Institute for Health Research Health Technology Assessment programme. The Health Services Research Unit and Health Economics Research Unit are core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate.

Health technology assessment (Winchester, England) · meta-analysis · 68 citationsread the source →

Prevalence of symptoms of anxiety and depression in patients with inflammatory bowel disease: a systematic review and meta-analysis.

Background: Inflammatory bowel disease (IBD) is a lifelong condition with no cure. Patients with IBD might experience symptoms of common mental disorders such as anxiety and depression because of bidirectional communication via the gut-brain axis and chronicity of symptoms, and because of impaired quality of life and reduced social functioning. However, uncertainties remain about the magnitude of this problem. We aimed to assess prevalence of symptoms of anxiety or depression in adult patients with IBD. Methods: In this systematic review and meta-analysis, we searched MEDLINE, Embase, Embase Classic, and PsycINFO for papers published from inception to Sept 30, 2020, reporting observational studies that recruited at least 100 adult patients with IBD and that reported prevalence of symptoms of anxiety or depression according to validated screening instruments. We excluded studies that only used a structured interview to assess for these symptoms and studies that did not provide extractable data. We extracted data from published study reports and calculated pooled prevalences of symptoms of anxiety and depression, odds ratios (OR), and 95% CIs. Findings: Of 5544 studies identified, 77 fulfilled the eligibility criteria, including 30 118 patients in total. Overall, pooled prevalence of anxiety symptoms was 32·1% (95% CI 28·3-36·0) in 58 studies (I2=96·9%) and pooled prevalence of depression symptoms was 25·2% (22·0-28·5) in 75 studies (I2=97·6%). In studies that reported prevalence of anxiety or depression in patients with Crohn's disease and ulcerative colitis within the same study population, patients with Crohn's disease had higher odds of anxiety symptoms (OR 1·2, 95% CI 1·1-1·4) and depression symptoms (1·2, 1·1-1·4) than patients with ulcerative colitis. Overall, women with IBD were more likely to have symptoms of anxiety than were men with IBD (pooled prevalence 33·8% [95% CI 26·5-41·5] for women vs 22·8% [18·7-27·2] for men; OR 1·7 [95% CI 1·2-2·3]). They were also more likely to have symptoms of depression than men were (pooled prevalence 21·2% [95% CI 15·4-27·6] for women vs 16·2% [12·6-20·3] for men; OR 1·3 [95% CI 1·0-1·8]). The prevalence of symptoms of anxiety (57·6% [95% CI 38·6-75·4]) or depression (38·9% [26·2-52·3]) was higher in patients with active IBD than in patients with inactive disease (38·1% [30·9-45·7] for anxiety symptoms and 24·2% [14·7-35·3] for depression symptoms; ORs 2·5 [95% CI 1·5-4·1] for anxiety and 3·1 [1·9-4·9] for depression). Interpretation: There is a high prevalence of symptoms of anxiety and depression in patients with IBD, with up to a third of patients affected by anxiety symptoms and a quarter affected by depression symptoms. Prevalence was also increased in patients with active disease: half of these patients met criteria for anxiety symptoms and a third met criteria for depression symptoms. Encouraging gastroenterologists to screen for and treat these disorders might improve outcomes for patients with IBD. Funding: None.

The lancet. Gastroenterology & hepatology · meta-analysis · 514 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 →

Effectiveness of brief alcohol interventions in primary care populations.

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

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

Cannabis-based medicines for chronic neuropathic pain in adults.

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

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

The Efficacy of Emotionally Focused Couples Therapy and Behavioral Couples Therapy: A Meta‐Analysis

Behavioral couple therapy (BCT) and emotionally focused couples therapy (EFCT) are well-established treatments to reduce couple distress. This meta-analysis summarizes the current state of knowledge on the efficacy of these two therapy methods by focusing on randomized controlled trials only. A literature search revealed 33 suitable primary studies (2,730 participants in total), all of them measuring relationship satisfaction. Robust-variance random-effects meta-analysis revealed medium effect sizes at post-test (overall: g = 0.60; BCT: g = 0.53; EFCT: g = 0.73) and small effect sizes of 6 months after treatment (overall: g = 0.44; BCT: g = 0.35; EFCT: g = 0.66), but these gains were not maintained after 12 months (BCT only: g = 0.06). Between the two therapy methods, no significant effect size differences could be found. Results have to be interpreted with caution due to potential publication bias.

Journal of Marital and Family Therapy · meta-analysis · 76 citationsread the source →

Efficacy of school-based interventions aimed at decreasing sugar-sweetened beverage consumption among adolescents: a systematic review.

Objective: To verify the efficacy of school-based interventions aimed at reducing sugar-sweetened beverage (SSB) consumption among adolescents in order to develop or improve public health interventions. Design: Systematic review of interventions targeting adolescents and/or the school environment. Setting: The following databases were investigated: MEDLINE/PubMed, PsycINFO, CINAHL and EMBASE. Proquest Dissertations and Theses was also investigated for unpublished trials. Subjects: Adolescents were defined as individuals between the ages of 12 and 17 years. Results: A total of thirty-six studies detailing thirty-six different interventions tested among independent samples (n 152 001) were included in the review. Twenty interventions were classified as educational/behavioural and ten were classified as legislative/environmental interventions. Only six interventions targeted both individuals and their environment. Over 70 % of all interventions, regardless of whether they targeted individuals, their environment or both, were effective in decreasing SSB consumption. Legislative/environmental studies had the highest success rate (90·0 %). Educational/behavioural interventions only and interventions that combined educational/behavioural and legislative/environmental approaches were almost equally effective in reducing SSB consumption with success rates of 65·0 and 66·7 %, respectively. Among the interventions that had an educational/behavioural component, 61·5 % were theory-based. The behaviour change techniques most frequently used in interventions were providing information about the health consequences of performing the behaviour (72·2 %), restructuring the physical environment (47·2 %), behavioural goal setting (36·1 %), self-monitoring of behaviour (33·3 %), threat to health (30·6 %) and providing general social support (30·6 %). Conclusions: School-based interventions show promising results to reduce SSB consumption among adolescents. A number of recommendations are made to improve future studies.

Public health nutrition · meta-analysis · 69 citationsread the source →

Exercise therapy for chronic fatigue syndrome.

Background: Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004. Objectives: The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.• Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).• Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).• Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone). Search methods: We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies SELECTION CRITERIA: Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy. Data collection and analysis: Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome. Main results: We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures. Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate-quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes. Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate. With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions. Authors' conclusions: Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention.

The Cochrane database of systematic reviews · meta-analysis · 80 citationsread the source →

Are interventions focused on gender-norms effective in preventing domestic violence against women in low and lower-middle income countries? A systematic review and meta-analysis.

Background: One in three women experience intimate partner violence worldwide, according to many primary studies. However, systematic review and meta-analysis of intimate partner violence is very limited. Therefore, we set to summarize the findings of existing primary studies to generate evidence for informed decisions to tackle domestic violence against women in low and lower-middle income countries. Methods: Studies were searched from main databases (Medline via PubMed, EMBASE, CINAHL, PopLine and Web of Science), Google scholar and other relevant sources using electronic and manual techniques. Published and unpublished studies written in English and conducted among women aged (15-49 years) from 1994 to 2017 were eligible. Data were extracted independently by two authors, and recorded in Microsoft Excel sheet. Heterogeneity between included studies was assessed using I2, and publication bias was explored using visual inspection of funnel plot. Statistical analysis was carried out to determine the pooled prevalence using Comprehensive Meta-Analysis software. In addition, sub-group analysis was carried out by study-setting and types of intimate partner violence. Results: Fifty two studies were included in the systematic review. Of these, 33 studies were included in the meta-analysis. The pooled prevalence of lifetime intimate partner violence was 55% (95% CI: 52, 59%). Of these, main categories were lifetime physical violence [39% (95% CI: 33, 45%); psychological violence [45% (95% CI: 40, 52%)] and sexual violence [20% (95% CI: 17, 23%)]. Furthermore, the pooled prevalence of current intimate partner violence was 38% (95% CI: 34, 43%). Of these, physical violence [25% (95% CI: 21, 28%)]; psychological violence [30% (95% CI: 24, 36%)] and sexual violence [7.0% (95% CI: 6.6, 7.5%)] were the pooled prevalence for the major types of intimate partner violence. In addition, concurrent intimate partner violence was 13% (95% CI: 12, 15%). Individual, relationship, community and societal level factors were associated with intimate partner violence. Traditional community gender-norm transformation, stakeholders' engagement, women's empowerment, intervention integration and policy/legal framework were highly recommended interventions to prevent intimate partner violence. Conclusion: Lifetime and current intimate partner violence is common and unacceptably high. Therefore, concerned bodies will need to design and implement strategies to transform traditional gender norms, engage stakeholders, empower women and integrate service to prevent violence against women. Protocol registration: PROSPERO: 2017: CRD42017079977 .

Reproductive health · meta-analysis · 43 citationsread the source →

Educational and psychological interventions for managing atopic dermatitis (eczema).

Background: Atopic dermatitis (eczema), can have a significant impact on well-being and quality of life for affected people and their families. Standard treatment is avoidance of triggers or irritants and regular application of emollients and topical steroids or calcineurin inhibitors. Thorough physical and psychological assessment is central to good-quality treatment. Overcoming barriers to provision of holistic treatment in dermatological practice is dependent on evaluation of the efficacy and economics of both psychological and educational interventions in this participant group. This review is based on a previous Cochrane review published in 2014, and now includes adults as well as children. Objectives: To assess the clinical outcomes of educational and psychological interventions in children and adults with atopic dermatitis (eczema) and to summarise the availability and principal findings of relevant economic evaluations. Search methods: We searched the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, APA PsycINFO and two trials registers up to March 2023. We checked the reference lists of included studies and related systematic reviews for further references to relevant randomised controlled trials (RCTs) and contacted experts in the field to identify additional studies. We searched NHS Economic Evaluation Database, MEDLINE and Embase for economic evaluations on 8 June 2022. Selection criteria: Randomised, cluster-randomised and cross-over RCTs that assess educational and psychological interventions for treating eczema in children and adults. Data collection and analysis: We used standard Cochrane methods, with GRADE to assess the certainty of the evidence for each outcome. Primary outcomes were reduction in disease severity, as measured by clinical signs, patient-reported symptoms and improvement in health-related quality-of-life (HRQoL) measures. Secondary outcomes were improvement in long-term control of symptoms, improvement in psychological well-being, improvement in standard treatment concordance and adverse events. We assessed short- (up to 16 weeks after treatment) and long-term time points (more than 16 weeks). Main results: We included 37 trials (6170 participants). Most trials were conducted in high-income countries (34/37), in outpatient settings (25/37). We judged three trials to be low risk of bias across all domains. Fifteen trials had a high risk of bias in at least one domain, mostly due to bias in measurement of the outcome. Trials assessed interventions compared to standard care. Individual educational interventions may reduce short-term clinical signs (measured by SCORing Atopic Dermatitis (SCORAD); mean difference (MD) -5.70, 95% confidence interval (CI) -9.39 to -2.01; 1 trial, 30 participants; low-certainty evidence) but patient-reported symptoms, HRQoL, long-term eczema control and psychological well-being were not reported. Group education interventions probably reduce clinical signs (SCORAD) both in the short term (MD -9.66, 95% CI -19.04 to -0.29; 3 studies, 731 participants; moderate-certainty evidence) and the long term (MD -7.22, 95% CI -11.01 to -3.43; 3 studies, 1424 participants; moderate-certainty evidence) and probably reduce long-term patient-reported symptoms (SMD -0.47 95% CI -0.60 to -0.33; 2 studies, 908 participants; moderate-certainty evidence). They may slightly improve short-term HRQoL (SMD -0.19, 95% CI -0.36 to -0.01; 4 studies, 746 participants; low-certainty evidence), but may make little or no difference to short-term psychological well-being (Perceived Stress Scale (PSS); MD -2.47, 95% CI -5.16 to 0.22; 1 study, 80 participants; low-certainty evidence). Long-term eczema control was not reported. We don't know whether technology-mediated educational interventions could improve short-term clinical signs (SCORAD; 1 study; 29 participants; very low-certainty evidence). They may have little or no effect on short-term patient-reported symptoms (Patient Oriented Eczema Measure (POEM); MD -0.76, 95% CI -1.84 to 0.33; 2 studies; 195 participants; low-certainty evidence) and probably have little or no effect on short-term HRQoL (MD 0, 95% CI -0.03 to 0.03; 2 studies, 430 participants; moderate-certainty evidence). Technology-mediated education interventions probably slightly improve long-term eczema control (Recap of atopic eczema (RECAP); MD -1.5, 95% CI -3.13 to 0.13; 1 study, 232 participants; moderate-certainty evidence), and may improve short-term psychological well-being (MD -1.78, 95% CI -2.13 to -1.43; 1 study, 24 participants; low-certainty evidence). Habit reversal treatment may reduce short-term clinical signs (SCORAD; MD -6.57, 95% CI -13.04 to -0.1; 1 study, 33 participants; low-certainty evidence) but we are uncertain about any effects on short-term HRQoL (Children's Dermatology Life Quality Index (CDLQI); 1 study, 30 participants; very low-certainty evidence). Patient-reported symptoms, long-term eczema control and psychological well-being were not reported. We are uncertain whether arousal reduction therapy interventions could improve short-term clinical signs (Eczema Area and Severity Index (EASI); 1 study, 24 participants; very low-certainty evidence) or patient-reported symptoms (visual analogue scale (VAS); 1 study, 18 participants; very low-certainty evidence). Arousal reduction therapy may improve short-term HRQoL (Dermatitis Family Impact (DFI); MD -2.1, 95% CI -4.41 to 0.21; 1 study, 91 participants; low-certainty evidence) and psychological well-being (PSS; MD -1.2, 95% CI -3.38 to 0.98; 1 study, 91 participants; low-certainty evidence). Long-term eczema control was not reported. No studies reported standard care compared with self-help psychological interventions, psychological therapies or printed education; or adverse events. We identified two health economic studies. One found that a 12-week, technology-mediated, educational-support programme may be cost neutral. The other found that a nurse practitioner group-education intervention may have lower costs than standard care provided by a dermatologist, with comparable effectiveness. Authors' conclusions: In-person, individual education, as an adjunct to conventional topical therapy, may reduce short-term eczema signs compared to standard care, but there is no information on eczema symptoms, quality of life or long-term outcomes. Group education probably reduces eczema signs and symptoms in the long term and may also improve quality of life in the short term. Favourable effects were also reported for technology-mediated education, habit reversal treatment and arousal reduction therapy. All favourable effects are of uncertain clinical significance, since they may not exceed the minimal clinically important difference (MCID) for the outcome measures used (MCID 8.7 points for SCORAD, 3.4 points for POEM). We found no trials of self-help psychological interventions, psychological therapies or printed education. Future trials should include more diverse populations, address shared priorities, evaluate long-term outcomes and ensure patients are involved in trial design.

The Cochrane database of systematic reviews · meta-analysis · 14 citationsread the source →

Multidisciplinary biopsychosocial rehabilitation for subacute low back pain.

Background: Low back pain (LBP) is associated with enormous personal and societal burdens, especially when it reaches the chronic stage of the disorder (pain for a duration of more than three months). Indeed, individuals who reach the chronic stage tend to show a more persistent course, and they account for the majority of social and economic costs. As a result, there is increasing emphasis on the importance of intervening at the early stages of LBP.According to the biopsychosocial model, LBP is a condition best understood with reference to an interaction of physical, psychological, and social influences. This has led to the development of multidisciplinary biopsychosocial rehabilitation (MBR) programs that target factors from the different domains, administered by healthcare professionals from different backgrounds. This review is an update of a Cochrane Review on MBR for subacute LBP, which was published in 2003. It is part of a series of reviews on MBR for musculoskeletal pain published by the Cochrane Back and Neck Group and the Cochrane Musculoskeletal Group. Objectives: To examine the effectiveness of MBR for subacute LBP (pain for a duration of six to 12 weeks) among adults, with a focus on pain, back-specific disability, and work status. Search methods: We searched for relevant trials in any language by a computer-aided search of CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO and two trials registers. Our search is current to 13 July 2016. Selection criteria: We included randomised controlled trials (RCTs) of adults with subacute LBP. We included studies that investigated a MBR program compared to any type of control intervention. We defined MBR as an intervention that included a physical component (e.g. pharmacological, physical therapy) in combination with either a psychological, social, or occupational component (or any combination of these). We also required involvement of healthcare professionals from at least two different clinical backgrounds with appropriate training to deliver the component for which they were responsible. Data collection and analysis: We used standard methodological procedures expected by Cochrane. In particular, the data extraction and 'risk of bias' assessment were conducted by two people, independently. We used the Cochrane tool to assess risk of bias and the GRADE approach to assess the overall quality of the evidence for each outcome. Main results: We included a total of nine RCTs (981 participants) in this review. Five studies were conducted in Europe and four in North America. Sample sizes ranged from 33 to 351. The mean age across trials ranged between 32.0 and 43.7 years. All included studies were judged as having high risk of performance bias and high risk of detection bias due to lack of blinding, and four of the nine studies suffered from at least one additional source of possible bias. In MBR compared to usual care for subacute LBP, individuals receiving MBR had less pain (four studies with 336 participants; SMD -0.46, 95% CI -0.70 to -0.21, moderate-quality of evidence due to risk of bias) and less disability (three studies with 240 participants; SMD -0.44, 95% CI -0.87 to -0.01, low-quality of evidence due to risk of bias and inconsistency), as well as increased likelihood of return-to-work (three studies with 170 participants; OR 3.19, 95% CI 1.46 to 6.98, very low-quality of evidence due to serious risk of bias and imprecision) and fewer sick leave days (two studies with 210 participants; SMD -0.38 95% CI -0.66 to -0.10, low-quality of evidence due to risk of bias and imprecision) at 12-month follow-up. The effect sizes for pain and disability were low in terms of clinical meaningfulness, whereas effects for work-related outcomes were in the moderate range. However, when comparing MBR to other treatments (i.e. brief intervention with features from a light mobilization program and a graded activity program, functional restoration, brief clinical intervention including education and advice on exercise, and psychological counselling), we found no differences between the groups in terms of pain (two studies with 336 participants; SMD -0.14, 95% CI -0.36 to 0.07, low-quality evidence due to imprecision and risk of bias), functional disability (two studies with 345 participants; SMD -0.03, 95% CI -0.24 to 0.18, low-quality evidence due to imprecision and risk of bias), and time away from work (two studies with 158 participants; SMD -0.25 95% CI -0.98 to 0.47, very low-quality evidence due to serious imprecision, inconsistency and risk of bias). Return-to-work was not reported in any of the studies. Although we looked for adverse events in both comparisons, none of the included studies reported this outcome. Authors' conclusions: On average, people with subacute LBP who receive MBR will do better than if they receive usual care, but it is not clear whether they do better than people who receive some other type of treatment. However, the available research provides mainly low to very low-quality evidence, thus additional high-quality trials are needed before we can describe the value of MBP for clinical practice.

The Cochrane database of systematic reviews · meta-analysis · 94 citationsread the source →

Assessment of parasympathetic reactivation after exercise.

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

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

Trajectories of 24-h movement guidelines from middle adolescence to adulthood on depression and suicidal ideation: a 22-year follow-up study.

Background: The 24-h movement guidelines for youth and adults recommend the specific duration of physical activity, sedentary time, and sleep duration to ensure optimal health, but little is known about its relationship to mental health indicators. The aim of the study was to explore the association between 24-h movement guidelines in adolescence and its trajectories from middle adolescence (12-17 years old) to adulthood (33-39 years old) with depression and suicidal ideation in adulthood. Methods: This prospective cohort study included individuals who participated in Waves I (1994-1995) and V (2016-2018) of the National Longitudinal Study of Adolescent Health (Add Health) in the United States. Physical activity, screen time and sleep duration were measured using questionnaires. Adults were categorized as having depression if they had a self-reported history of depression and/or prescription medication-use for depression in the previous four weeks. Suicidal ideation was assessed by a self-reported single question in both waves. Poisson regression analyses were used to estimate the incidence rate ratio (IRR) of depression and suicidal ideation at adulthood, according to meeting specific and combinations of 24-h movement guidelines at Wave I and its trajectories from adolescence to adulthood. Results: The study included 7,069 individuals (56.8% women). Adolescents who met physical activity guidelines and all three guidelines at middle adolescence had lower risk of depression (IRR = 0.84, 95%CI 0.72 to 0.98) and suicidal ideation (IRR = 0.74, 95%CI 0.55 to 0.99) at adulthood than those who did not meet any of these guidelines, respectively. Individuals who met the guidelines for screen time and all three guidelines in both adolescence and adulthood had lower risk of depression (screen time, IRR = 0.87, 95% CI 0.72 to 0.98; all three, IRR = 0.37, 95% CI 0.15 to 0.92) and suicidal ideation (screen time, IRR = 0.74, 95% CI 0.51 to 0.97; all three, IRR = 0.12, 95% CI 0.06 to 0.33) than those who never met the guidelines. Additionally, individuals who did not meet all three guidelines in adolescence but met the guidelines in adulthood had lower risk of suicidal ideation than those who never met the guidelines (IRR = 0.81, 95%CI 0.45 to 0.89). Conclusion: Our findings highlight the importance of promoting and maintaining adherence to the 24-h movement guidelines from middle adolescence to adulthood to prevent mental health problems. However, our findings must be interpreted carefully due to declared limitations, e.g., the self-reported assessments which are subject to sources of error and bias or that the dataset used to gauge meeting a guidelines (1994-1996) was made later (2016).

The international journal of behavioral nutrition and physical activity · 28 citationsread the source →

Brief Behavioral Interventions for Substance Use in Adolescents: A Meta-analysis.

Context: Adolescents with problematic substance use (SU) are at risk for far-reaching adverse outcomes. Objective: Synthesize the evidence regarding the effects of brief behavioral interventions for adolescents (12-20 years) with problematic SU. Data sources: We conducted literature searches in Medline, the Cochrane Central Register of Controlled Trials, Embase, Cumulative Index to Nursing and Allied Health Literature, and PsycInfo through October 31, 2019. Study selection: We screened 33 272 records and citations for interventions in adolescents with at least problematic SU, retrieved 1831 articles, and selected 22 randomized controlled trials of brief interventions meeting eligibility criteria for meta-analysis. Data extraction: We followed Agency for Healthcare Research and Quality guidelines. We categorized brief interventions into components, including motivational interviewing (MI), psychoeducation, and treatment as usual. Outcomes included SU (abstinence, days used per month) for alcohol and cannabis, and substance-related problem scales. Strength of evidence (SoE) was assessed. Results: Both pairwise and network meta-analyses were conducted by using random effects models. Compared to treatment as usual, the use of MI reduces heavy alcohol use days by 0.7 days per month (95% credible interval [CrI]: -1.6 to 0.02; low SoE), alcohol use days by 1.1 days per month (95% CrI -2.2 to -0.3; moderate SoE), and overall substance-related problems by a standardized net mean difference of 0.5 (95% CrI -1.0 to 0; low SoE). The use of MI did not reduce cannabis use days, with a net mean difference of -0.05 days per month (95% CrI: -0.26 to 0.14; moderate SoE). Limitations: There was lack of consistently reported outcomes and limited available comparisons. Conclusions: The use of MI reduces heavy alcohol use, alcohol use days, and SU-related problems in adolescents but does not reduce cannabis use days.

Pediatrics · systematic review · 56 citationsread the source →

Social Return on Investment (SROI) methodology to account for value for money of public health interventions: a systematic review.

Background: Increased scarcity of public resources has led to a concomitant drive to account for value-for-money of interventions. Traditionally, cost-effectiveness, cost-utility and cost-benefit analyses have been used to assess value-for-money of public health interventions. The social return on investment (SROI) methodology has capacity to measure broader socio-economic outcomes, analysing and computing views of multiple stakeholders in a singular monetary ratio. This review provides an overview of SROI application in public health, explores lessons learnt from previous studies and makes recommendations for future SROI application in public health. Methods: A systematic review of peer-reviewed and grey literature to identify SROI studies published between January 1996 and December 2014 was conducted. All articles describing conduct of public health SROI studies and which reported a SROI ratio were included. An existing 12-point framework was used to assess study quality. Data were extracted using pre-developed codes: SROI type, type of commissioning organisation, study country, public health area in which SROI was conducted, stakeholders included in study, discount rate used, SROI ratio obtained, time horizon of analysis and reported lessons learnt. Results: 40 SROI studies, of varying quality, including 33 from high-income countries and 7 from low middle-income countries, met the inclusion criteria. SROI application increased since its first use in 2005 until 2011, declining afterwards. SROI has been applied across different public health areas including health promotion (12 studies), mental health (11), sexual and reproductive health (6), child health (4), nutrition (3), healthcare management (2), health education and environmental health (1 each). Qualitative and quantitative methods have been used to gather information for public health SROI studies. However, there remains a lack of consensus on who to include as beneficiaries, how to account for counterfactual and appropriate study-time horizon. Reported SROI ratios vary widely (1.1:1 to 65:1). Conclusions: SROI can be applied across healthcare settings. Best practices such as analysis involving only beneficiaries (not all stakeholders), providing justification for discount rates used in models, using purchasing power parity equivalents for monetary valuations and incorporating objective designs such as case-control or before-and-after designs for accounting for outcomes will improve robustness of public health SROI studies.

BMC public health · systematic review · 93 citationsread the source →

Pharmacological and electronic cigarette interventions for smoking cessation in adults: component network meta-analyses.

Background: Tobacco smoking is the leading preventable cause of death and disease worldwide. Stopping smoking can reduce this harm and many people would like to stop. There are a number of medicines licenced to help people quit globally, and e-cigarettes are used for this purpose in many countries. Typically treatments work by reducing cravings to smoke, thus aiding initial abstinence and preventing relapse. More information on comparative effects of these treatments is needed to inform treatment decisions and policies. Objectives: To investigate the comparative benefits, harms and tolerability of different smoking cessation pharmacotherapies and e-cigarettes, when used to help people stop smoking tobacco. Search methods: We identified studies from recent updates of Cochrane Reviews investigating our interventions of interest. We updated the searches for each review using the Cochrane Tobacco Addiction Group (TAG) specialised register to 29 April 2022. Selection criteria: We included randomised controlled trials (RCTs), cluster-RCTs and factorial RCTs, which measured smoking cessation at six months or longer, recruited adults who smoked combustible cigarettes at enrolment (excluding pregnant people) and randomised them to approved pharmacotherapies and technologies used for smoking cessation worldwide (varenicline, cytisine, nortriptyline, bupropion, nicotine replacement therapy (NRT) and e-cigarettes) versus no pharmacological intervention, placebo (control) or another approved pharmacotherapy. Studies providing co-interventions (e.g. behavioural support) were eligible if the co-intervention was provided equally to study arms. Data collection and analysis: We followed standard Cochrane methods for screening, data extraction and risk of bias (RoB) assessment (using the RoB 1 tool). Primary outcome measures were smoking cessation at six months or longer, and the number of people reporting serious adverse events (SAEs). We also measured withdrawals due to treatment. We used Bayesian component network meta-analyses (cNMA) to examine intervention type, delivery mode, dose, duration, timing in relation to quit day and tapering of nicotine dose, using odds ratios (OR) and 95% credibility intervals (CrIs). We calculated an effect estimate for combination NRT using an additive model. We evaluated the influence of population and study characteristics, provision of behavioural support and control arm rates using meta-regression. We evaluated certainty using GRADE. Main results: Of our 332 eligible RCTs, 319 (835 study arms, 157,179 participants) provided sufficient data to be included in our cNMA. Of these, we judged 51 to be at low risk of bias overall, 104 at high risk and 164 at unclear risk, and 118 reported pharmaceutical or e-cigarette/tobacco industry funding. Removing studies at high risk of bias did not change our interpretation of the results. Benefits We found high-certainty evidence that nicotine e-cigarettes (OR 2.37, 95% CrI 1.73 to 3.24; 16 RCTs, 3828 participants), varenicline (OR 2.33, 95% CrI 2.02 to 2.68; 67 RCTs, 16,430 participants) and cytisine (OR 2.21, 95% CrI 1.66 to 2.97; 7 RCTs, 3848 participants) were associated with higher quit rates than control. In absolute terms, this might lead to an additional eight (95% CrI 4 to 13), eight (95% CrI 6 to 10) and seven additional quitters per 100 (95% CrI 4 to 12), respectively. These interventions appeared to be more effective than the other interventions apart from combination NRT (patch and a fast-acting form of NRT), which had a lower point estimate (calculated additive effect) but overlapping 95% CrIs (OR 1.93, 95% CrI 1.61 to 2.34). There was also high-certainty evidence that nicotine patch alone (OR 1.37, 95% CrI 1.20 to 1.56; 105 RCTs, 37,319 participants), fast-acting NRT alone (OR 1.41, 95% CrI 1.29 to 1.55; 120 RCTs, 31,756 participants) and bupropion (OR 1.43, 95% CrI 1.26 to 1.62; 71 RCTs, 14,759 participants) were more effective than control, resulting in two (95% CrI 1 to 3), three (95% CrI 2 to 3) and three (95% CrI 2 to 4) additional quitters per 100 respectively. Nortriptyline is probably associated with higher quit rates than control (OR 1.35, 95% CrI 1.02 to 1.81; 10 RCTs, 1290 participants; moderate-certainty evidence), resulting in two (CrI 0 to 5) additional quitters per 100. Non-nicotine/placebo e-cigarettes (OR 1.16, 95% CrI 0.74 to 1.80; 8 RCTs, 1094 participants; low-certainty evidence), equating to one additional quitter (95% CrI -2 to 5), had point estimates favouring the intervention over control, but CrIs encompassed the potential for no difference and harm. There was low-certainty evidence that tapering the dose of NRT prior to stopping treatment may improve effectiveness; however, 95% CrIs also incorporated the null (OR 1.14, 95% CrI 1.00 to 1.29; 111 RCTs, 33,156 participants). This might lead to an additional one quitter per 100 (95% CrI 0 to 2). Harms There were insufficient data to include nortriptyline and non-nicotine EC in the final SAE model. Overall rates of SAEs for the remaining treatments were low (average 3%). Low-certainty evidence did not show a clear difference in the number of people reporting SAEs for nicotine e-cigarettes, varenicline, cytisine or NRT when compared to no pharmacotherapy/e-cigarettes or placebo. Bupropion may slightly increase rates of SAEs, although the CrI also incorporated no difference (moderate certainty). In absolute terms bupropion may cause one more person in 100 to experience an SAE (95% CrI 0 to 2). Authors' conclusions: The most effective interventions were nicotine e-cigarettes, varenicline and cytisine (all high certainty), as well as combination NRT (additive effect, certainty not rated). There was also high-certainty evidence for the effectiveness of nicotine patch, fast-acting NRT and bupropion. Less certain evidence of benefit was present for nortriptyline (moderate certainty), non-nicotine e-cigarettes and tapering of nicotine dose (both low certainty). There was moderate-certainty evidence that bupropion may slightly increase the frequency of SAEs, although there was also the possibility of no increased risk. There was no clear evidence that any other tested interventions increased SAEs. Overall, SAE data were sparse with very low numbers of SAEs, and so further evidence may change our interpretation and certainty. Future studies should report SAEs to strengthen certainty in this outcome. More head-to-head comparisons of the most effective interventions are needed, as are tests of combinations of these. Future work should unify data from behavioural and pharmacological interventions to inform approaches to combined support for smoking cessation.

The Cochrane database of systematic reviews · systematic review · 114 citationsread the source →

Outcomes of childhood epilepsy at age 33 years: a population-based birth-cohort study.

Purpose: There is uncertainty about health and socioeconomic outcomes of children with epilepsy, knowledge of adult outcomes, and factors associated with adverse outcomes are essential to guide prognosis, improve management, and determine appropriate allocation of resources. Methods: A subgroup of 101 children with epilepsy (onset ≤ age 16 years) were previously identified and reported from the 1958 National Child Development Study (NCDS), a national United Kingdom birth cohort study. In the current study we examine outcomes of this unique childhood epilepsy subgroup at age 33 compared to unaffected NCDS cohort members in mental and general health, education and employment, marriage, and parenthood. Multivariable regression analyses were used to investigate factors (including etiology, cognitive development, parental interest, and childhood anxiety/depression at age 11 years) associated with adverse outcomes. key findings: Sixty-five (66%) were still participating at 33 years. Median follow-up after epilepsy onset was 28 years (range 17-33 years). Thirty participants [46%, 95% confidence interval (CI) 35-58] had epilepsy onset <5 years, 32 (49%, 95% CI 37-61) had "symptomatic" epilepsy, and 33 (51%, 95% CI 39-63) had idiopathic epilepsy. Thirty-one participants (48%) reported being seen by their doctor for epilepsy in the preceding year, 27 (42%) were registered disabled, 39 (60%) had a drivers license, and 42 (65%) thought their epilepsy made it harder to get/keep a paid job. People who had childhood epilepsy had an increased risk of death [standardized mortality rate (SMR) 3.1, 95% CI 1.1-6.1]. Childhood epilepsy was associated with poor general and mental health at 33 years on univariable analyses, but not after adjusting for childhood cognitive development/comorbidities and anxiety over acceptance by peers/adults at age 11. Childhood epilepsy was an independent risk factor for not being married [odds ratio (OR) 0.45, 95% CI 0.05-0.94] or being a parent (OR 0.67, 95% CI 0.42-0.91). People with childhood epilepsy and poor cognitive development compared to those with poor cognitive development without epilepsy had a greater proportion with subsequent poor mental health (56% vs. 24%, difference in proportion 33%, 95% CI 12-50), and a lesser proportion who married (39% vs. 78%, difference in proportion -39%, 95% CI -56 to -19). Significance: Compared to the unaffected population, children with epilepsy with good cognitive development/without comorbidities have similar adult health, educational, and employment outcomes but have difficulties with establishing and maintaining personal relationships. A combination of having childhood epilepsy plus poor cognitive development is more likely to be associated with adverse outcomes compared to having poor cognitive development without childhood epilepsy. Children with epilepsy have increased risk of death compared to the rest of the population. Pharmacologic management alone is inadequate and long-term psychosocial support is needed.

Epilepsia · 46 citationsread the source →

Social feedback processing from early to late adolescence: influence of sex, age, and attachment style.

Objective: The establishment of an accurate understanding of one's social context is a central developmental task during adolescence. A critical component of such development is to learn how to integrate the objective evaluation of one's behavior with the social response to the latter--here referred to as social feedback processing. Case report: We measured brain activity by means of fMRI in 33 healthy adolescents (12-19 years old, 14 females). Participants played a difficult perceptual game with integrated verbal and visual feedback. Verbal feedback provided the participants with objective performance evaluation (won vs. lost). Visual feedback consisted of either smiling or angry faces, representing positive or negative social evaluations. Together, the combination of verbal and visual feedback gave rise to congruent versus incongruent social feedback combinations. In addition to assessing sex differences, we further tested for the effects of age and attachment style on social feedback processing. Results revealed that brain activity during social feedback processing was significantly modulated by sex, age, and attachment style in prefrontal cortical areas, ventral anterior cingulate cortex, anterior insula, caudate, and amygdala/hippocampus. We found indication for heightened activity during incongruent social feedback processing in females, older participants, and individuals with an anxious attachment style. Conversely, we observed stronger activity during processing of congruent social feedback in males and participants with an avoidant attachment style. Conclusion: Our findings not only extend knowledge on the typical development of socio-emotional brain function during adolescence, but also provide first clues on how attachment insecurities, and particularly attachment avoidance, could interfere with the latter mechanisms.

Brain and behavior · 36 citationsread the source →

Effect of Telephone Cognitive Behavioral Therapy for Insomnia in Older Adults With Osteoarthritis Pain: A Randomized Clinical Trial.

Importance: Scalable delivery models of cognitive behavioral therapy for insomnia (CBT-I), an effective treatment, are needed for widespread implementation, particularly in rural and underserved populations lacking ready access to insomnia treatment. Objective: To evaluate the effectiveness of telephone CBT-I vs education-only control (EOC) in older adults with moderate to severe osteoarthritis pain. Design, setting, and participants: This is a randomized clinical trial of 327 participants 60 years and older who were recruited statewide through Kaiser Permanente Washington from September 2016 to December 2018. Participants were double screened 3 weeks apart for moderate to severe insomnia and osteoarthritis (OA) pain symptoms. Blinded assessments were conducted at baseline, after 2 months posttreatment, and at 12-month follow-up. Interventions: Six 20- to 30-minute telephone sessions provided over 8 weeks. Participants submitted daily diaries and received group-specific educational materials. The CBT-I instruction included sleep restriction, stimulus control, sleep hygiene, cognitive restructuring, and homework. The EOC group received information about sleep and OA. Main outcomes and measures: The primary outcome was score on the Insomnia Severity Index (ISI) at 2 months posttreatment and 12-month follow-up. Secondary outcomes included pain (score on the Brief Pain Inventory-short form), depression (score on the 8-item Patient Health Questionnaire), and fatigue (score on the Flinders Fatigue Scale). Results: Of the 327 participants, the mean (SD) age was 70.2 (6.8) years, and 244 (74.6%) were women. In the 282 participants with follow-up ISI data, the total 2-month posttreatment ISI scores decreased 8.1 points in the CBT-I group and 4.8 points in the EOC group, an adjusted mean between-group difference of -3.5 points (95% CI, -4.4 to -2.6 points; P < .001). Results were sustained at 12-month follow-up (adjusted mean difference, -3.0 points; 95% CI, -4.1 to -2.0 points; P < .001). At 12-month follow-up, 67 of 119 (56.3%) participants receiving CBT-I remained in remission (ISI score, ≤7) compared with 33 of 128 (25.8%) participants receiving EOC. Fatigue was also significantly reduced in the CBT-I group compared with the EOC group at 2 months posttreatment (mean between-group difference, -2.0 points; 95% CI, -3.1 to -0.9 points; P = <.001) and 12-month follow-up (mean between-group difference, -1.8 points; 95% CI, -3.1 to -0.6 points; P = .003). Posttreatment significant differences were observed for pain, but these differences were not sustained at 12-month follow-up. Conclusions and relevance: In this randomized clinical trial, telephone CBT-I was effective in improving sleep, fatigue, and, to a lesser degree, pain among older adults with comorbid insomnia and OA pain in a large statewide health plan. Results support provision of telephone CBT-I as an accessible, individualized, effective, and scalable insomnia treatment. Trial registration: Clinical Trials.gov Identifier: NCT02946957.

JAMA internal medicine · randomised controlled trial · 69 citationsread the source →

Smartphone-Enhanced Symptom Management In Psychosis: Open, Randomized Controlled Trial.

Background: Improving recovery from acute symptoms and preventing relapse are two significant challenges in severe mental illness. We developed a personalized smartphone-based app to monitor symptoms in real time and validated its acceptance, reliability, and validity. Objective: To assess (i) acceptability of continuous monitoring to SMI patients and health professionals over 3 months; (ii) impact of active self-monitoring on positive psychotic symptoms assessed at 6 and 12 weeks; and (iii) the feasibility of detecting early warning signs of relapse. Methods: The active symptom monitoring smartphone app was built into an end-to-end system in two NHS Trusts to enable real-time symptom self-monitoring and detection by the clinical team of early signs of relapse in people with severe mental illness. We conducted an open randomized controlled trial of active symptom monitoring compared to usual management to assess: (i) acceptability and safety of continuous monitoring over 3 months; (ii) impact of active self-monitoring on positive psychotic symptoms assessed at 6 and 12 weeks; (iii) feasibility of detecting early warning signs of relapse communicated to the healthcare staff via an app streaming data to the electronic health record. Eligible participants with a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) diagnosis of schizophrenia and related disorders, and a history of relapse within the previous two years were enrolled from an early intervention team and a community mental health team. Results: Of 181 eligible patients, 81 (45%) consented and were randomized to either active symptom monitoring or management as usual. At 12 weeks, 90% (33/36) of those in the active monitoring group continued to use the system and exhibited an adherence rate (defined as responding to >33% of alerts) of 84% (30/36}. Active symptom monitoring was associated with no difference on the empowerment scale in comparison to the usual management group at 12 weeks. The pre-planned intent-to-treat analysis of the primary outcome, a positive score on the Positive and Negative Syndrome Scale (PANSS) scale, showed a significant reduction in the active symptom monitoring group over 12 weeks in the early intervention center. Alerts for personalized early warning signs of relapse were built into the workflows of both NHS Trusts, and 100% of health professional staff used the system in a new digital workflow. Qualitative analyses supported the acceptability of the system to participants and staff. Conclusions: The active smartphone monitoring system is feasible and was accepted by users in a 3-month study of people with severe mental illness, with surprisingly high levels of adherence. App use was associated with psychotic symptom improvement in recent-onset participants, but not those with longstanding illness, supporting the notion of improved self-management. When built into clinical management workflows to enable personalized alerts of symptom deterioration, the app has demonstrated utility in promoting earlier intervention for relapse. Trial registration: ISRCTN Registry ISRCTN88145142; http://www.isrctn.com/ISRCTN88145142.

Journal of medical Internet research · randomised controlled trial · 45 citationsread the source →

Clinical and economic outcomes of remotely delivered cognitive behaviour therapy versus treatment as usual for repeat unscheduled care users with severe health anxiety: a multicentre randomised controlled trial.

Background: It is challenging to engage repeat users of unscheduled healthcare with severe health anxiety in psychological help and high service costs are incurred. We investigated whether clinical and economic outcomes were improved by offering remote cognitive behaviour therapy (RCBT) using videoconferencing or telephone compared to treatment as usual (TAU). Methods: A single-blind, parallel group, multicentre randomised controlled trial was undertaken in primary and general hospital care. Participants were aged ≥18 years with ≥2 unscheduled healthcare contacts within 12 months and scored >18 on the Health Anxiety Inventory. Randomisation to RCBT or TAU was stratified by site, with allocation conveyed to a trial administrator, research assessors masked to outcome. Data were collected at baseline, 3, 6, 9 and 12 months. The primary outcome was change in HAI score from baseline to six months on an intention-to-treat basis. Secondary outcomes were generalised anxiety, depression, physical symptoms, function and overall health. Health economics analysis was conducted from a health service and societal perspective. Results: Of the 524 patients who were referred and assessed for trial eligibility, 470 were eligible and 156 (33%) were recruited; 78 were randomised to TAU and 78 to RCBT. Compared to TAU, RCBT significantly reduced health anxiety at six months, maintained to 9 and 12 months (mean change difference HAI -2.81; 95% CI -5.11 to -0.50; P = 0.017). Generalised anxiety, depression and overall health was significantly improved at 12 months, but there was no significant change in physical symptoms or function. RCBT was strictly dominant with a net monetary benefit of £3,164 per participant at a willingness to pay threshold of £30,000. No treatment-related adverse events were reported in either group. Conclusions: RCBT may reduce health anxiety, general anxiety and depression and improve overall health, with considerable reductions in health and informal care costs in repeat users of unscheduled care with severe health anxiety who have previously been difficult to engage in psychological treatment. RCBT may be an easy-to-implement intervention to improve clinical outcome and save costs in one group of repeat users of unscheduled care. Trial registration: The trial was registered at ClinicalTrials.gov on 19 Nov 2014 with reference number NCT02298036.

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

Effectiveness of Mindfulness Meditation vs Headache Education for Adults With Migraine: A Randomized Clinical Trial.

Importance: Migraine is the second leading cause of disability worldwide. Most patients with migraine discontinue medications due to inefficacy or adverse effects. Mindfulness-based stress reduction (MBSR) may provide benefit. Objective: To determine if MBSR improves migraine outcomes and affective/cognitive processes compared with headache education. Design, setting, and participants: This randomized clinical trial of MBSR vs headache education included 89 adults who experienced between 4 and 20 migraine days per month. There was blinding of participants (to active vs comparator group assignments) and principal investigators/data analysts (to group assignment). Interventions: Participants underwent MBSR (standardized training in mindfulness/yoga) or headache education (migraine information) delivered in groups that met for 2 hours each week for 8 weeks. Main outcomes and measures: The primary outcome was change in migraine day frequency (baseline to 12 weeks). Secondary outcomes were changes in disability, quality of life, self-efficacy, pain catastrophizing, depression scores, and experimentally induced pain intensity and unpleasantness (baseline to 12, 24, and 36 weeks). Results: Most participants were female (n = 82, 92%), with a mean (SD) age of 43.9 (13.0) years, and had a mean (SD) of 7.3 (2.7) migraine days per month and high disability (Headache Impact Test-6: 63.5 [5.7]), attended class (median attendance, 7 of 8 classes), and followed up through 36 weeks (33 of 45 [73%] of the MBSR group and 32 of 44 [73%] of the headache education group). Participants in both groups had fewer migraine days at 12 weeks (MBSR: -1.6 migraine days per month; 95% CI, -0.7 to -2.5; headache education: -2.0 migraine days per month; 95% CI, -1.1 to -2.9), without group differences (P = .50). Compared with those who participated in headache education, those who participated in MBSR had improvements from baseline at all follow-up time points (reported in terms of point estimates of effect differences between groups) on measures of disability (5.92; 95% CI, 2.8-9.0; P < .001), quality of life (5.1; 95% CI, 1.2-8.9; P = .01), self-efficacy (8.2; 95% CI, 0.3-16.1; P = .04), pain catastrophizing (5.8; 95% CI, 2.9-8.8; P < .001), depression scores (1.6; 95% CI, 0.4-2.7; P = .008), and decreased experimentally induced pain intensity and unpleasantness (MBSR group: 36.3% [95% CI, 12.3% to 60.3%] decrease in intensity and 30.4% [95% CI, 9.9% to 49.4%] decrease in unpleasantness; headache education group: 13.5% [95% CI, -9.9% to 36.8%] increase in intensity and an 11.2% [95% CI, -8.9% to 31.2%] increase in unpleasantness; P = .004 for intensity and .005 for unpleasantness, at 36 weeks). One reported adverse event was deemed unrelated to study protocol. Conclusions and relevance: Mindfulness-based stress reduction did not improve migraine frequency more than headache education, as both groups had similar decreases; however, MBSR improved disability, quality of life, self-efficacy, pain catastrophizing, and depression out to 36 weeks, with decreased experimentally induced pain suggesting a potential shift in pain appraisal. In conclusion, MBSR may help treat total migraine burden, but a larger, more definitive study is needed to further investigate these results. Trial registration: ClinicalTrials.gov Identifier: NCT02695498.

JAMA internal medicine · randomised controlled trial · 132 citationsread the source →

Randomized controlled trial investigating the effects of a breastfeeding relaxation intervention on maternal psychological state, breast milk outcomes, and infant behavior and growth.

Background: Biological signaling and communication between mothers and infants during breastfeeding may shape infant behavior and feeding. This signaling is complex and little explored in humans, although it is potentially relevant for initiatives to improve breastfeeding rates. Objectives: The aim of this study was to investigate physiological and psychological aspects of mother-infant signaling during breastfeeding experimentally, testing the effects of a relaxation intervention on maternal psychological state, breast milk intake, milk cortisol levels, and infant behavior and growth. Methods: Primiparous breastfeeding mothers and full-term infants were randomly assigned to receive relaxation therapy [intervention relaxation group; n = 33 (RG)] or to the control group [n = 31 (CG); no relaxation therapy] at 2 wk postpartum. Both groups received standard breastfeeding support. Home visits were conducted at 2 (HV1), 6 (HV2), 12 (HV3) and 14 (HV4) wk to measure maternal stress and anxiety, breast milk intake and milk cortisol, and infant behavior and growth. Results: RG mothers had lower stress scores postintervention than the CG (HV3 ∆ = -3.13; 95% CI: -5.9, -0.3) and lower hindmilk cortisol at HV1 (∆ = -44.5%; 95% CI: -76.1%, -12.9%) but not at HV2. RG infants had longer sleep duration (∆ = 82 min/d; 95% CI: 16, 149 min/d) at HV2 and higher gains in weight and body mass index standardized deviation score than the CG infants (∆ = 0.76; 95% CI: 0.3, 1.22; and ∆ = 0.59; 95% CI: 0.09, 1.1, respectively). RG infants had a mean milk intake at HV3 that was 227 g/d higher than that of the CG infants (P = 0.031) after controlling for gender and milk intake at HV1. Conclusions: The trial shows the effectiveness of a simple relaxation intervention for improving maternal and infant outcomes and identifies some potential signaling mechanisms for investigation in future and larger studies, especially in settings where mothers are more stressed, such as those with preterm or low birth weight infants. This trial was registered at clinicaltrials.gov as NCT01971216.

The American journal of clinical nutrition · randomised controlled trial · 66 citationsread the source →

The EMPOWER blended digital intervention for relapse prevention in schizophrenia: a feasibility cluster randomised controlled trial in Scotland and Australia.

Background: Early warning signs monitoring by service users with schizophrenia has shown promise in preventing relapse but the quality of evidence is low. We aimed to establish the feasibility of undertaking a definitive randomised controlled trial to determine the effectiveness of a blended digital intervention for relapse prevention in schizophrenia. Methods: This multicentre, feasibility, cluster randomised controlled trial aimed to compare Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery (EMPOWER) with treatment as usual in community mental health services (CMHS) in Glasgow and Melbourne. CMHS were the unit of randomisation, selected on the basis of those that probably had five or more care coordinators willing to participate. Participants were eligible if they were older than 16 years, had a schizophrenia or related diagnosis confirmed via case records, were able to provide informed consent, had contact with CMHS, and had had a relapse within the previous 2 years. Participants were randomised within stratified clusters to EMPOWER or to continue their usual approach to care. EMPOWER blended a smartphone for active monitoring of early warning signs with peer support to promote self-management and clinical triage to promote access to relapse prevention. Main outcomes were feasibility, acceptability, usability, and safety, which was assessed through face-to-face interviews. App usage was assessed via the smartphone and self-report. Primary end point was 12 months. Participants, research assistants and other team members involved in delivering the intervention were not masked to treatment conditions. Assessment of relapse was done by an independent adjudication panel masked to randomisation group. The study is registered at ISRCTN (99559262). Findings: We identified and randomised eight CMHS (six in Glasgow and two in Melbourne) comprising 47 care coordinators. We recruited 86 service users between Jan 19 and Aug 8, 2018; 73 were randomised (42 [58%] to EMPOWER and 31 [42%] to treatment as usual). There were 37 (51%) men and 36 (49%) women. At 12 months, main outcomes were collected for 32 (76%) of service users in the EMPOWER group and 30 (97%) of service users in the treatment as usual group. Of those randomised to EMPOWER, 30 (71%) met our a priori criterion of more than 33% adherence to daily monitoring that assumed feasibility. Median time to discontinuation of these participants was 31·5 weeks (SD 14·5). There were 29 adverse events in the EMPOWER group and 25 adverse events in the treatment as usual group. There were 13 app-related adverse events, affecting 11 people, one of which was serious. Fear of relapse was lower in the EMPOWER group than in the treatment as usual group at 12 months (mean difference -7·53 (95% CI -14·45 to 0·60; Cohen's d -0·53). Interpretation: A trial of digital technology to monitor early warning signs blended with peer support and clinical triage to detect and prevent relapse appears to be feasible, safe, and acceptable. A further main trial is merited. Funding: UK National Institute for Health Research Health Technology Assessment programme and the Australian National Health and Medical Research Council.

The lancet. Psychiatry · randomised controlled trial · 50 citationsread the source →

Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression.

Background: Psilocybin is being studied for use in treatment-resistant depression. Methods: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits). Results: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; P<0.001) and between the 10-mg group and 1-mg group was -2.5 (95% CI, -6.2 to 1.2; P = 0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups. Conclusions: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. (Funded by COMPASS Pathfinder; EudraCT number, 2017-003288-36; ClinicalTrials.gov number, NCT03775200.).

The New England journal of medicine · randomised controlled trial · 786 citationsread the source →

A randomised controlled trial of dietary improvement for adults with major depression (the 'SMILES' trial).

Background: The possible therapeutic impact of dietary changes on existing mental illness is largely unknown. Using a randomised controlled trial design, we aimed to investigate the efficacy of a dietary improvement program for the treatment of major depressive episodes. Methods: 'SMILES' was a 12-week, parallel-group, single blind, randomised controlled trial of an adjunctive dietary intervention in the treatment of moderate to severe depression. The intervention consisted of seven individual nutritional consulting sessions delivered by a clinical dietician. The control condition comprised a social support protocol to the same visit schedule and length. Depression symptomatology was the primary endpoint, assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) at 12 weeks. Secondary outcomes included remission and change of symptoms, mood and anxiety. Analyses utilised a likelihood-based mixed-effects model repeated measures (MMRM) approach. The robustness of estimates was investigated through sensitivity analyses. Results: We assessed 166 individuals for eligibility, of whom 67 were enrolled (diet intervention, n = 33; control, n = 34). Of these, 55 were utilising some form of therapy: 21 were using psychotherapy and pharmacotherapy combined; 9 were using exclusively psychotherapy; and 25 were using only pharmacotherapy. There were 31 in the diet support group and 25 in the social support control group who had complete data at 12 weeks. The dietary support group demonstrated significantly greater improvement between baseline and 12 weeks on the MADRS than the social support control group, t(60.7) = 4.38, p < 0.001, Cohen's d = -1.16. Remission, defined as a MADRS score <10, was achieved for 32.3% (n = 10) and 8.0% (n = 2) of the intervention and control groups, respectively (χ 2 (1) = 4.84, p = 0.028); number needed to treat (NNT) based on remission scores was 4.1 (95% CI of NNT 2.3-27.8). A sensitivity analysis, testing departures from the missing at random (MAR) assumption for dropouts, indicated that the impact of the intervention was robust to violations of MAR assumptions. Conclusions: These results indicate that dietary improvement may provide an efficacious and accessible treatment strategy for the management of this highly prevalent mental disorder, the benefits of which could extend to the management of common co-morbidities. Trial registration: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000251820 . Registered on 29 February 2012.

BMC medicine · randomised controlled trial · 586 citationsread the source →

Psychological interventions to reduce suicidality in high-risk patients with major depression: a randomized controlled trial.

Background: Positive psychological constructs have been associated with reduced suicidal ideation, and interventions to cultivate positive feelings have the potential to reduce suicide risk. This study compares the efficacy of a 6-week, telephone-based positive psychology (PP) intervention against a cognition-focused (CF) control intervention among patients recently hospitalized for depression and suicidal ideation or behavior. Method: A total of 65 adults with a current major depressive episode reporting suicidal ideation or a recent suicide attempt were enrolled from participating in-patient psychiatric units. Prior to discharge, participants were randomized to the PP (n = 32) or CF (n = 33) intervention. In both interventions, participants received a treatment manual, performed weekly PP (e.g. gratitude letter) or CF (e.g. recalling daily events) exercises, and completed weekly one-on-one telephone sessions over 6 weeks. Between-group differences in hopelessness (primary outcome), depression, suicidality and positive psychological constructs at 6 and 12 weeks were tested using mixed-effects models accounting for intensity of post-hospitalization psychiatric treatment. Results: Compared with PP, the CF intervention was associated with significantly greater improvements in hopelessness at 6 weeks (β = -3.15, 95% confidence interval -6.18 to -0.12, effect size = -0.84, p = 0.04), but not 12 weeks. Similarly, the CF intervention led to greater improvements in depression, suicidal ideation, optimism and gratitude at 6 and 12 weeks. Conclusions: Contrary to our hypothesis, the CF intervention was superior to PP in improving hopelessness, other suicide risk factors and positive psychological constructs during a key post-discharge period among suicidal patients with depression. Further study of this CF intervention is warranted in populations at high suicide risk.

Psychological medicine · randomised controlled trial · 42 citationsread the source →

Online positive-oriented counseling, taking vitamin D3 tablet, online lifestyle modification training on premenstrual syndrome: a 3-armed randomized clinical trial.

Lack of absolute treatment for premenstrual syndrome (PMS), its cyclic nature, considerable prevalence (70-90%), and its mental and physical burden imply necessity of effectiveness comparison of various treatments. Although antidepressant and hormonal drugs are well-known medications for PMS, in affected women who can't tolerate, or don't have compatibility or compliance with these drugs, other effective treatments have always been important concern. This study aimed to compare effectiveness of online positive-oriented counseling, taking vitamin D3 tablet, and online lifestyle modification training on alleviating PMS. 3-armed parallel randomized clinical trial was performed on 84 20-40-year-old eligible women with PMS. 84 women were randomly ( www.random.org/sequenc ) allocated into three groups, but data of 77 women (1, n = 25) online positive-oriented counseling group (6 sessions), (2, n = 27) vitamin D3 tablet group (one vitamin D3 tablet weekly for 6 weeks), and (3, n = 25) online lifestyle training group (6 sessions) were analyzed. Vitamin D3 was measured at baseline, week6 and fallow up week10. Primary outcome variable PMS was measured with Premenstrual Symptoms Screening Tool (PSST) at baseline, week 6, and follow-up week 10. Primary outcome satisfaction with intervention method was measured using satisfaction scale at week 6 and follow-up week 10. ANOVA, Repeated Measures, and Paired samples t-test were used for statistical analysis. There was no statistically significant difference in PMS at baseline between three groups respectively (33 ± 5.8, 34.1 ± 7.1, & 35.2 ± 6.4, P = 0.500). However, at follow-up week 10, there was statistically significant difference between three groups (22.3 ± 4.3, 25.4 ± 6.5, & 31.8 ± 6.5; P < 0.001), with greatest improvement in online positive-oriented counseling group (P < 0.001). Satisfaction differed significantly among three groups at week 6 (51 ± 6.8, 46.4 ± 12, & 42.3 ± 6.3, P = 0.001) and follow-up week 10 (55.7 ± 11.6, 51.4 ± 12; & 43 ± 3.3, P < 0.001), with most satisfaction in positive-oriented counseling group (P < 0.001). All three interventions alleviated PMS, but online positive-oriented counseling was more effective and satisfying. Superiority of positive-oriented counseling implies mechanism of adaptation, better relationships, forgiveness, self-mood-regulation, and feasibility of its skills that could be continued individually by women after counseling completion. It is recommended health providers, health policymakers and managers support use of these interventions in treatment program and clinical guidelines. Trial registration: RCT registration number: IRCT20191231045967N1, Registration date:11/02/2020, Registration timing: prospective (IRCT | Survey the effect of vitamin D3 tablet intake, positivism group consulting with changing in life style in the treatment of premenstrual syndrome in women).

Scientific reports · randomised controlled trial · 4 citationsread the source →

Digital smartphone intervention to recognise and manage early warning signs in schizophrenia to prevent relapse: the EMPOWER feasibility cluster RCT.

Background: Relapse is a major determinant of outcome for people with a diagnosis of schizophrenia. Early warning signs frequently precede relapse. A recent Cochrane Review found low-quality evidence to suggest a positive effect of early warning signs interventions on hospitalisation and relapse. Objective: How feasible is a study to investigate the clinical effectiveness and cost-effectiveness of a digital intervention to recognise and promptly manage early warning signs of relapse in schizophrenia with the aim of preventing relapse? Design: A multicentre, two-arm, parallel-group cluster randomised controlled trial involving eight community mental health services, with 12-month follow-up. Settings: Glasgow, UK, and Melbourne, Australia. Participants: Service users were aged > 16 years and had a schizophrenia spectrum disorder with evidence of a relapse within the previous 2 years. Carers were eligible for inclusion if they were nominated by an eligible service user. Interventions: The Early signs Monitoring to Prevent relapse in psychosis and prOmote Wellbeing, Engagement, and Recovery (EMPOWER) intervention was designed to enable participants to monitor changes in their well-being daily using a mobile phone, blended with peer support. Clinical triage of changes in well-being that were suggestive of early signs of relapse was enabled through an algorithm that triggered a check-in prompt that informed a relapse prevention pathway, if warranted. Main outcome measures: The main outcomes were feasibility of the trial and feasibility, acceptability and usability of the intervention, as well as safety and performance. Candidate co-primary outcomes were relapse and fear of relapse. Results: We recruited 86 service users, of whom 73 were randomised (42 to EMPOWER and 31 to treatment as usual). Primary outcome data were collected for 84% of participants at 12 months. Feasibility data for people using the smartphone application (app) suggested that the app was easy to use and had a positive impact on motivations and intentions in relation to mental health. Actual app usage was high, with 91% of users who completed the baseline period meeting our a priori criterion of acceptable engagement (> 33%). The median time to discontinuation of > 33% app usage was 32 weeks (95% confidence interval 14 weeks to ∞). There were 8 out of 33 (24%) relapses in the EMPOWER arm and 13 out of 28 (46%) in the treatment-as-usual arm. Fewer participants in the EMPOWER arm had a relapse (relative risk 0.50, 95% confidence interval 0.26 to 0.98), and time to first relapse (hazard ratio 0.32, 95% confidence interval 0.14 to 0.74) was longer in the EMPOWER arm than in the treatment-as-usual group. At 12 months, EMPOWER participants were less fearful of having a relapse than those in the treatment-as-usual arm (mean difference -4.29, 95% confidence interval -7.29 to -1.28). EMPOWER was more costly and more effective, resulting in an incremental cost-effectiveness ratio of £3041. This incremental cost-effectiveness ratio would be considered cost-effective when using the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year gained. Limitations: This was a feasibility study and the outcomes detected cannot be taken as evidence of efficacy or effectiveness. Conclusions: A trial of digital technology to monitor early warning signs that blended with peer support and clinical triage to detect and prevent relapse is feasible. Future work: A main trial with a sample size of 500 (assuming 90% power and 20% dropout) would detect a clinically meaningful reduction in relapse (relative risk 0.7) and improvement in other variables (effect sizes 0.3-0.4). Trial registration: This trial is registered as ISRCTN99559262. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 27. See the NIHR Journals Library website for further project information. Funding in Australia was provided by the National Health and Medical Research Council (APP1095879).

Health technology assessment (Winchester, England) · randomised controlled trial · 24 citationsread the source →