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Life course health consequences and associated annual costs of adverse childhood experiences across Europe and North America: a systematic review and meta-analysis.

Background: An increasing number of studies are identifying associations between adverse childhood experiences (ACEs) and ill health throughout the life course. We aimed to calculate the proportions of major risk factors for and causes of ill health that are attributable to one or multiple types of ACE and the associated financial costs. Methods: In this systematic review and meta-analysis, we searched for studies in which risk data in individuals with ACEs were compared with these data in those without ACEs. We searched six electronic databases (MEDLINE, CINAHL, PsycINFO, Applied Social Sciences Index and Abstracts, Criminal Justice Databases, and the Education Resources Information Center) for quantitative studies published between Jan 1, 1990, and July 11, 2018, that reported risks of health-related behaviours and causes of ill health in adults that were associated with cumulative measures of ACEs (ie, number of ACEs). We included studies in adults in populations that did not have a high risk of ACEs, that had sample sizes of at least 1000 people, and that provided ACE prevalence data. We calculated the pooled RR for risk factors (harmful alcohol use, illicit drug use, smoking, and obesity) and causes of ill health (cancer, diabetes, cardiovascular disease, respiratory disease, anxiety, and depression) associated with ACEs. RRs were used to estimate the population-attributable fractions (PAFs) of risk attributable to ACEs and the disability-adjusted life-years (DALYs) and financial costs associated with ACEs. This study was prospectively registered in PROSPERO (CRD42018090356). Findings: Of 4387 unique articles found following our initial search, after review of the titles (and abstracts, when the title was relevant), we assessed 880 (20%) full-text articles. We considered 221 (25%) full-text articles for inclusion, of which 23 (10%) articles met all selection criteria for our meta-analysis. We found a pooled prevalence of 23·5% of individuals (95% CI 18·7-28·5) with one ACE and 18·7% (14·7-23·2) with two or more ACEs in Europe (from ten studies) and of 23·4% of individuals (22·0-24·8) with one ACE and 35·0% (31·6-38·4) with two or more ACEs in north America (from nine studies). Illicit drug use had the highest PAFs associated with ACEs of all the risk factors assessed in both regions (34·1% in Europe; 41·1% in north America). In both regions, PAFs of causes of ill health were highest for mental illness outcomes: ACEs were attributed to about 30% of cases of anxiety and 40% of cases of depression in north America and more than a quarter of both conditions in Europe. Costs of cardiovascular disease attributable to ACEs were substantially higher than for most other causes of ill health because of higher DALYs for this condition. Total annual costs attributable to ACEs were estimated to be US$581 billion in Europe and $748 billion in north America. More than 75% of these costs arose in individuals with two or more ACEs. Interpretation: Millions of adults across Europe and north America live with a legacy of ACEs. Our findings suggest that a 10% reduction in ACE prevalence could equate to annual savings of 3 million DALYs or $105 billion. Programmes to prevent ACEs and moderate their effects are available. Rebalancing expenditure towards ensuring safe and nurturing childhoods would be economically beneficial and relieve pressures on health-care systems. Funding: World Health Organization Regional Office for Europe.

The Lancet. Public health · meta-analysis · 660 citationsread the source →

Smoking cessation for people with severe mental illness (SCIMITAR+): a pragmatic randomised controlled trial.

Background: People with severe mental illnesses such as schizophrenia are three times more likely to smoke than the wider population, contributing to widening health inequalities. Smoking remains the largest modifiable risk factor for this health inequality, but people with severe mental illness have not historically engaged with smoking cessation services. We aimed to test the effectiveness of a combined behavioural and pharmacological smoking cessation intervention targeted specifically at people with severe mental illness. Methods: In the smoking cessation intervention for severe mental illness (SCIMITAR+) trial, a pragmatic, randomised controlled study, we recruited heavy smokers with bipolar disorder or schizophrenia from 16 primary care and 21 community-based mental health sites in the UK. Participants were eligible if they were aged 18 years or older, and smoked at least five cigarettes per day. Exclusion criteria included substantial comorbid drug or alcohol problems and people who lacked capacity to consent at the time of recruitment. Using computer-generated random numbers, participants were randomly assigned (1:1) to a bespoke smoking cessation intervention or to usual care. Participants, mental health specialists, and primary care physicians were unmasked to assignment. The bespoke smoking cessation intervention consisted of behavioural support from a mental health smoking cessation practitioner and pharmacological aids for smoking cessation, with adaptations for people with severe mental illness-such as, extended pre-quit sessions, cut down to quit, and home visits. Access to pharmacotherapy was via primary care after discussion with the smoking cessation specialist. Under usual care participants were offered access to local smoking cessation services not specifically designed for people with severe mental illnesses. The primary endpoint was smoking cessation at 12 months ascertained via carbon monoxide measurements below 10 parts per million and self-reported cessation for the past 7 days. Secondary endpoints were biologically verified smoking cessation at 6 months; number of cigarettes smoked per day, Fagerström Test for Nicotine Dependence (FTND) and Motivation to Quit (MTQ) questionnaire; general and mental health functioning determined via the Patient Health Questionnaire-9 (PHQ-9), the Generalised Anxiety Disorder-7 (GAD-7) questionnaire, and 12-Item Short Form Health Survey (SF-12); and body-mass index (BMI). This trial was registerd with the ISRCTN registry, number ISRCTN72955454, and is complete. Findings: Between Oct 7, 2015, and Dec 16, 2016, 526 eligible patients were randomly assigned to the bespoke smoking cessation intervention (n=265) or usual care (n=261). 309 (59%) participants were male, median age was 47·2 years (IQR 36·3-54·5), with high nicotine dependence (mean 24 cigarettes per day [SD 13·2]), and the most common severe mental disorders were schizophrenia or other psychotic illness (n=343 [65%]), bipolar disorder (n=115 [22%]), and schizoaffective disorder (n=66 [13%]). 234 (88%) of intervention participants engaged with the treatment programme and attended 6·4 (SD 3·5) quit smoking sessions, with an average duration of 39 min (SD 17; median 35 min, range 5-120). Verified quit data at 12 months were available for 219 (84%) of 261 usual care and 223 (84%) of 265 intervention participants. The proportion of participants who had quit at 12 months was higher in the intervention group than in the usual care group, but non-significantly (34 [15%] of 223 [13% of those assigned to group] vs 22 [10%] of 219 [8% of those assigned to group], risk difference 5·2%, 95% CI -1·0 to 11·4; odds ratio [OR] 1·6, 95% CI 0·9 to 2·9; p=0·10). The proportion of participants who quit at 6 months was significantly higher in the intervention group than in the usual care group (32 [14%] of 226 vs 14 [6%] of 217; risk difference 7·7%, 95% CI 2·1 to 13·3; OR 2·4, 95% CI 1·2 to 4·6; p=0·010). The incidence rate ratio for number of cigarettes smoked per day at 6 months was 0·90 (95% CI 0·80 to 1·01; p=0·079), and at 12 months was 1·00 (0·89 to 1·13; p=0·95). At both 6 months and 12 months, the intervention group was non-significantly favoured in the FTND (adjusted mean difference 6 months -0·18, 95% CI -0·53 to 0·17, p=0·32; and 12 months -0·01, -0·39 to 0·38, p=0·97) and MTQ questionnaire (adjusted mean difference 0·58, -0·01 to 1·17, p=0·056; and 12 months 0·64, 0·04 to 1·24, p=0·038). The PHQ-9 showed no difference between the groups (adjusted mean difference at 6 months 0·20, 95% CI -0·85 to 1·24 vs 12 months -0·12, -1·18 to 0·94). For the SF-12 survey, we saw evidence of improvement in physical health in the intervention group at 6 months (adjusted mean difference 1·75, 95% CI 0·21 to 3·28), but this difference was not evident at 12 months (0·59, -1·07 to 2·26); and we saw no difference in mental health between the groups at 6 or 12 months (adjusted mean difference at 6 months -0·73, 95% CI -2·82 to 1·36, and 12 months -0·41, -2·35 to 1·53). The GAD-7 questionnaire showed no difference between the groups (adjusted mean difference at 6 months -0·32 95% CI -1·26 to 0·62 vs 12 months -0·10, -1·05 to 0·86). No difference in BMI was seen between the groups (adjusted mean difference 6 months 0·16, 95% CI -0·54 to 0·85; 12 months 0·25, -0·62 to 1·13). Interpretation: This bespoke intervention is a candidate model of smoking cessation for clinicians and policy makers to address high prevalence of smoking. The incidence of quitting at 6 months shows that smoking cessation can be achieved, but the waning of this effect by 12 months means more effort is needed for sustained quitting. Funding: National Institute for Health Research Health Technology Assessment Programme.

The lancet. Psychiatry · randomised controlled trial · 134 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 →

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

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

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

Health and financial costs of adverse childhood experiences in 28 European countries: a systematic review and meta-analysis.

Background: Adverse childhood experiences (ACEs) are associated with increased health risks across the life course. We aimed to estimate the annual health and financial burden of ACEs for 28 European countries. Methods: In this systematic review and meta-analysis, we searched MEDLINE, CINAHL, PsycINFO, Applied Social Sciences Index and Abstracts, Criminal Justice Databases, and Education Resources Information Center for quantitative studies (published Jan 1, 1990, to Sept 8, 2020) that reported prevalence of ACEs and risks of health outcomes associated with ACEs. Pooled relative risks were calculated for associations between ACEs and harmful alcohol use, smoking, illicit drug use, high body-mass index, depression, anxiety, interpersonal violence, cancer, type 2 diabetes, cardiovascular disease, stroke, and respiratory disease. Country-level ACE prevalence was calculated using available data. Country-level population attributable fractions (PAFs) due to ACEs were generated and applied to 2019 estimates of disability-adjusted life-years. Financial costs (US$ in 2019) were estimated using an adapted human capital approach. Findings: In most countries, interpersonal violence had the largest PAFs due to ACEs (range 14·7-53·5%), followed by harmful alcohol use (15·7-45·0%), illicit drug use (15·2-44·9%), and anxiety (13·9%-44·8%). Harmful alcohol use, smoking, and cancer had the highest ACE-attributable costs in many countries. Total ACE-attributable costs ranged from $0·1 billion (Montenegro) to $129·4 billion (Germany) and were equivalent to between 1·1% (Sweden and Turkey) and 6·0% (Ukraine) of nations' gross domestic products. Interpretation: Availability of ACE data varies widely between countries and country-level estimates cannot be directly compared. However, findings suggest ACEs are associated with major health and financial costs across European countries. The cost of not investing to prevent ACEs must be recognised, particularly as countries look to recover from the COVID-19 pandemic, which interrupted services and education, and potentially increased risk factors for ACEs. Funding: WHO Regional Office for Europe.

The Lancet. Public health · meta-analysis · 140 citationsread the source →

Integration of pre-exposure prophylaxis services into public HIV care clinics in Kenya: a pragmatic stepped-wedge randomised trial.

Background: Successful and sustainable models for HIV pre-exposure prophylaxis (PrEP) delivery in public health systems in Africa are needed. We aimed to evaluate the implementation of PrEP delivery integrated in public HIV care clinics in Kenya. Methods: As part of Kenya's national PrEP roll-out, we conducted a stepped-wedge cluster-randomised pragmatic trial to catalyse scale-up of PrEP delivery integrated in 25 public HIV care clinics. We selected high-volume clinics in these regions (ie, those with a high number of people living with HIV enrolled in HIV care and treatment). Clinics (each representing a cluster) were stratified by region and randomly assigned to the order in which clinic staff would receive PrEP training and ongoing technical support using numbered opaque balls picked from a bag. There was no masking. PrEP provision was done by clinic staff without additional financial support. Data were abstracted from records of individuals initiating PrEP. The primary outcome was the number of people initiating PrEP per clinic per month comparing intervention to control periods. Other outcomes included PrEP continuation, adherence, and incident HIV infections. This trial is registered with ClinicalTrials.gov, NCT03052010. Findings: After the baseline period, which started in January, 2017, every month two to six HIV care clinics crossed over from control to intervention, until August, 2017, when all clinics were implementing the intervention. Of 4898 individuals initiating PrEP (27 during the control period and 4871 during the intervention period), 2640 (54%) were women, the median age was 31 years (IQR 25-39), and 4092 (84%) reported having a partner living with HIV. The mean monthly number of PrEP initiations per clinic was 0·1 (SD 0·5) before the intervention and 7·5 (2·7) after intervention introduction (rate ratio 23·7, 95% CI 14·2-39·5, p<0·0001). PrEP continuation was 57% at 1 month, 44% at 3 months, and 34% at 6 months, and 12% of those who missed a refill returned later for PrEP re-initiation. Tenofovir diphosphate was detected in 68 (96%) of 71 blood samples collected from a randomly selected subset of participants. Six HIV infections were observed over 2531 person-years of observation (incidence 0·24 cases per 100 person-years), three of which occurred at the first visit after PrEP initiation. Interpretation: We observed high uptake, reasonable continuation with high adherence, frequent PrEP restarts, and low HIV incidence. Integration of PrEP services within public HIV care clinics in Africa is feasible. Funding: National Institute of Mental Health and Bill & Melinda Gates Foundation.

The Lancet. Global health · randomised controlled trial · 40 citationsread the source →

Extracorporeal life support during cardiac arrest and cardiogenic shock: a systematic review and meta-analysis.

Purpose: Veno-arterial extracorporeal life support (ECLS) is increasingly used in patients during cardiac arrest and cardiogenic shock, to support both cardiac and pulmonary function. We performed a systematic review and meta-analysis of cohort studies comparing mortality in patients treated with and without ECLS support in the setting of refractory cardiac arrest and cardiogenic shock complicating acute myocardial infarction. Methods: We systematically searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the publisher subset of PubMed updated to December 2015. Thirteen studies were included of which nine included cardiac arrest patients (n = 3098) and four included patients with cardiogenic shock after acute myocardial infarction (n = 235). Data were pooled by a Mantel-Haenzel random effects model and heterogeneity was examined by the I 2 statistic. Results: In cardiac arrest, the use of ECLS was associated with an absolute increase of 30 days survival of 13 % compared with patients in which ECLS was not used [95 % CI 6-20 %; p < 0.001; number needed to treat (NNT) 7.7] and a higher rate of favourable neurological outcome at 30 days (absolute risk difference 14 %; 95 % CI 7-20 %; p < 0.0001; NNT 7.1). Propensity matched analysis, including 5 studies and 438 patients (219 in both groups), showed similar results. In cardiogenic shock, ECLS showed a 33 % higher 30-day survival compared with IABP (95 % CI, 14-52 %; p < 0.001; NNT 13) but no difference when compared with TandemHeart/Impella (-3 %; 95 % CI -21 to 14 %; p = 0.70; NNH 33). Conclusions: In cardiac arrest, the use of ECLS was associated with an increased survival rate as well as an increase in favourable neurological outcome. In the setting of cardiogenic shock there was an increased survival with ECLS compared with IABP.

Intensive care medicine · meta-analysis · 353 citationsread the source →

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

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

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

Therapist-guided remote versus in-person cognitive behavioural therapy: a systematic review and meta-analysis of randomized controlled trials.

Background: Cognitive behavioural therapy (CBT) has been shown to be effective for several psychiatric and somatic conditions; however, most randomized controlled trials (RCTs) have administered treatment in person and whether remote delivery is similarly effective remains uncertain. We sought to compare the effectiveness of therapist-guided remote CBT and in-person CBT. Methods: We systematically searched MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials from inception to July 4, 2023, for RCTs that enrolled adults (aged ≥ 18 yr) presenting with any clinical condition and that randomized participants to either therapist-guided remote CBT (e.g., teleconference, videoconference) or in-person CBT. Paired reviewers assessed risk of bias and extracted data independently and in duplicate. We performed random-effects model meta-analyses to pool patient-important primary outcomes across eligible RCTs as standardized mean differences (SMDs). We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance to assess the certainty of evidence and used the Instrument to Assess the Credibility of Effect Modification Analyses (ICEMAN) to rate the credibility of subgroup effects. Results: We included 54 RCTs that enrolled a total of 5463 patients. Seventeen studies focused on treatment of anxiety and related disorders, 14 on depressive symptoms, 7 on insomnia, 6 on chronic pain or fatigue syndromes, 5 on body image or eating disorders, 3 on tinnitus, 1 on alcohol use disorder, and 1 on mood and anxiety disorders. Moderate-certainty evidence showed little to no difference in the effectiveness of therapist-guided remote and in-person CBT on primary outcomes (SMD -0.02, 95% confidence interval -0.12 to 0.07). Interpretation: Moderate-certainty evidence showed little to no difference in the effectiveness of in-person and therapist-guided remote CBT across a range of mental health and somatic disorders, suggesting potential for the use of therapist-guided remote CBT to facilitate greater access to evidence-based care. Systematic review registration: Open Science Framework (https://osf.io/7asrc).

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · meta-analysis · 24 citationsread the source →

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

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

Epilepsia · randomised controlled trial · 251 citationsread the source →

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

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

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

The association between loneliness, social isolation and inflammation: A systematic review and meta-analysis.

The review synthesised evidence examining the association between a. loneliness with inflammation and b. social isolation with inflammation in adults aged 16 or older from the general population. From an initial 7,400 articles we identified 14 papers that examined loneliness, and 16 that examined social isolation. Qualitative syntheses indicated mixed results, variable study quality, and methodological heterogeneity. Most studies provided associations for C-reactive protein CRP, fibrinogen and Interleukin-6 IL-6, and these results were synthesised using random-effects meta-analyses. There was no association between loneliness with CRP or fibrinogen, but there was a significant association between loneliness and IL-6 for most-adjusted but not least-adjusted analyses. There was also a significant least-adjusted association between social isolation with CRP and fibrinogen, which remained significant for fibrinogen in most-adjusted analyses. There was no association between social isolation with IL-6. Sensitivity analyses indicated that methodological heterogeneity impacted on results. Results indicate that social isolation and loneliness could be linked with systemic inflammation, but more robust methodology is needed to confirm these associations and unpack mechanisms.

Neuroscience and biobehavioral reviews · meta-analysis · 198 citationsread the source →

Randomized proof of concept trial of GLYX-13, an N-methyl-D-aspartate receptor glycine site partial agonist, in major depressive disorder nonresponsive to a previous antidepressant agent.

Background: Approximately 45% of patients with major depressive disorder (MDD) do not remit when treated with biogenic amine antidepressants. Consequently, there is a significant need for antidepressant agents with different mechanisms of action. Early proof of concept (POC) studies with such novel agents play a significant role in helping drug developers identify agents and mechanisms of action that merit more intensive research. Studies have demonstrated that high affinity N-methyl-Daspartate (NMDA) receptor blockers (eg, ketamine) can produce rapid antidepressant effects in patients who have not responded to currently available agents, but treatment with these agents is accompanied by psychotomimetic effects that make their use problematic. This column describes a POC study involving GLYX-13, an N-methyl-D-aspartate receptor glycine site functional partial agonist. Method: In this double-blind, randomized, placebo-controlled study, a single intravenous (IV) dose of GLYX-13 (1, 5, 10, or 30 mg/kg) or placebo was administered to 116 subjects with MDD who had not benefitted from a trial of at least one biogenic amine antidepressant during the current episode. The primary outcome measure was score on the Hamilton Depression Rating Scale-17 (Ham-D17), which was used to rate overall depressive symptoms at baseline and at 24 hours and days 3, 7, 14, and, in some arms, days 21 and 28 after administration. Results: GLYX-13, 5 or 10 mg/kg IV, reduced depressive symptoms as assessed by the Ham-D17 at days 1 through 7. Onset of action as assessed using the Bech-6 occurred within 2 hours. GLYX-13 did not elicit psychotomimetic or other significant side effects. Conclusion: In this early POC study, GLYX-13 reduced depressive symptoms within 2 hours and this effect was maintained for 7 days on average in subjects with MDD who had not responded to another antidepressant agent during the current depressive episode. The findings of this study support the hypothesis that modulation of the NMDA receptor is a valid target for the development of antidepressant drugs and the need for additional studies to further evaluate the effects of GLYX-13. POC studies such as the one described here play a pivotal role in allowing drug researchers to decide whether to move forward with larger and more expensive studies, and they enable them to focus available resources on those molecules that appear to have the most therapeutic promise. Based on the POC study described here, a multiple dose study has been completed which showed sustained therapeutic benefit with repeated dosing of GLYX-13 for more than 6 weeks. Phase 3 studies are now being planned.

Journal of psychiatric practice · randomised controlled trial · 139 citationsread the source →

Promoting well-being in refugee children: An exploratory controlled trial of a positive psychology intervention delivered in Greek refugee camps.

Rigorously evaluated interventions that target protective factors and positive resources rather than ameliorating negative outcomes in child refugees are rare. To address this, we developed and evaluated a short, group-based resilience-building intervention called Strengths for the Journey (SFJ), which was designed for war-affected children. We conducted a quasi-randomized pilot study of the SFJ intervention with 72 7- to 14-year-old forcibly displaced children (Mage = 10.76, 64.8% female) in three refugee camps in Lesvos, Greece. Intervention effectiveness was assessed by measuring pre-post changes in well-being, self-esteem, optimism, and depressive symptoms from before (T1) to immediately after the intervention/wait-list task (T2). Four focus group interviews were conducted with 31 of the participants to discuss their views on the effects of the intervention and the continued use of the skills that were learned. Using repeated-measures ANOVAs, we found improvements in well-being, F (1, 46) = 42.99, ηp2 = .48, self-esteem, F (1, 56) = 29.11, ηp2 = .40, optimism, F (1, 53) = 27.16, ηp2 = .34, and depressive symptoms, F (1, 31) = 62.14, ηp2 = .67, in the intervention group compared with the wait-listed group (p < .05). Focus group participants highlighted the importance of SFJ in developing a sense of togetherness and building their strengths. Child refugees in low-resource settings may benefit from brief, first-line interventions that target protective factors such as well-being, hope, self-esteem, and belonging.

Development and psychopathology · randomised controlled trial · 24 citationsread the source →

Adoption, reach, and implementation of a cancer education intervention in African American churches.

Background: Use of technology is increasing in health promotion and has continued growth potential in intervention research. Guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, this paper reports on the adoption, reach, and implementation of Project HEAL (Health through Early Awareness and Learning)-a community-based implementation trial of a cancer educational intervention in 14 African American churches. We compare adoption, reach, and implementation at the organizational and participant level for churches in which lay peer community health advisors (CHAs) were trained using traditional classroom didactic methods compared with a new online system. Methods: Fifteen churches were randomized to one of two study groups in which two CHAs per church were trained through either classroom ("Traditional"; n = 16 CHAs in 8 churches) or web-based ("Technology"; n = 14 CHAs in 7 churches) training methods. Once trained and certified, all CHAs conducted a series of three group educational workshops in their churches on cancer early detection (breast, prostate, and colorectal). Adoption, reach, and implementation were assessed using multiple data sources including church-level data, participant engagement in the workshops, and study staff observations of CHA performance. Results: The project had a 41% overall adoption rate at the church level. In terms of reach, a total of 375 participants enrolled in Project HEAL-226 participants in the Traditional group (43% reach) and 149 in the Technology group (21% reach; p < .10). Implementation was evaluated in terms of adherence, dosage, and quality. All churches fully completed the three workshops; however, the Traditional churches took somewhat longer (M = 84 days) to complete the workshop series than churches in the Technology group (M = 64 days). Other implementation outcomes were comparable between both the Traditional and Technology groups (p > .05). Conclusions: Overall, the Project HEAL intervention had reasonable adoption, though reach could have been better. Implementation was strong across both study groups, suggesting the promise of using web-based methods to disseminate and implement evidence-based interventions in faith-based settings and other areas where community health educators work to eliminate health disparities.

Implementation science : IS · randomised controlled trial · 40 citationsread the source →

Preoperative physiotherapy for the prevention of respiratory complications after upper abdominal surgery: pragmatic, double blinded, multicentre randomised controlled trial.

Objective: To assess the efficacy of a single preoperative physiotherapy session to reduce postoperative pulmonary complications (PPCs) after upper abdominal surgery. Design: Prospective, pragmatic, multicentre, patient and assessor blinded, parallel group, randomised placebo controlled superiority trial. Setting: Multidisciplinary preadmission clinics at three tertiary public hospitals in Australia and New Zealand. Participants: 441 adults aged 18 years or older who were within six weeks of elective major open upper abdominal surgery were randomly assigned through concealed allocation to receive either an information booklet (n=219; control) or preoperative physiotherapy (n=222; intervention) and followed for 12 months. 432 completed the trial. Interventions: Preoperatively, participants received an information booklet (control) or an additional 30 minute physiotherapy education and breathing exercise training session (intervention). Education focused on PPCs and their prevention through early ambulation and self directed breathing exercises to be initiated immediately on regaining consciousness after surgery. Postoperatively, all participants received standardised early ambulation, and no additional respiratory physiotherapy was provided. Main outcome measures: The primary outcome was a PPC within 14 postoperative hospital days assessed daily using the Melbourne group score. Secondary outcomes were hospital acquired pneumonia, length of hospital stay, utilisation of intensive care unit services, and hospital costs. Patient reported health related quality of life, physical function, and post-discharge complications were measured at six weeks, and all cause mortality was measured to 12 months. Results: The incidence of PPCs within 14 postoperative hospital days, including hospital acquired pneumonia, was halved (adjusted hazard ratio 0.48, 95% confidence interval 0.30 to 0.75, P=0.001) in the intervention group compared with the control group, with an absolute risk reduction of 15% (95% confidence interval 7% to 22%) and a number needed to treat of 7 (95% confidence interval 5 to 14). No significant differences in other secondary outcomes were detected. Conclusion: In a general population of patients listed for elective upper abdominal surgery, a 30 minute preoperative physiotherapy session provided within existing hospital multidisciplinary preadmission clinics halves the incidence of PPCs and specifically hospital acquired pneumonia. Further research is required to investigate benefits to mortality and length of stay. Trial registration: Australian New Zealand Clinical Trials Registry ANZCTR 12613000664741.

BMJ (Clinical research ed.) · randomised controlled trial · 169 citationsread the source →

Emollients improve treatment results with topical corticosteroids in childhood atopic dermatitis: a randomized comparative study.

The aim of the study was to investigate whether adding emollients to the standard topical corticosteroid therapy influences the outcome of children with atopic dermatitis. Fifty-two children aged between 2 and 12 yr were divided randomly in two subgroups consisting of 26 children each. Both groups applied 0.1% methylprednisolone aceponate cream on lesional atopic skin once daily for 2 wk and were observed for another 4 wk after treatment discontinuation. Group B used additionally emollients for the whole study period. Patients were evaluated at days 0 (baseline), 7, 14 (end of therapy), 28 and 42 (follow-up). Both groups demonstrated significant improvement of disease severity according to EASI (Eczema Area and Severity Index) scale (group A: 6.8 +/- 3.59 before and 0.87 +/- 1.25 after therapy, p < 0.001; group B: 9.6 +/- 8.39 before and 1.11 +/- 2.37 after therapy, p < 0.001). Xerosis improved significantly better in group B compared to group A, both clinically (group A: 1.38 +/- 0.57 scores before and 1.5 +/- 0.58 scores after therapy, p = 0.11; group B: 1.62 +/- 0.64 scores before and 0.12 +/- 0.33 scores after therapy, p < 0.001), and by corneometry assessment (group A: 41.7 +/- 9.1 units before and 51.3 +/- 11.3 units after therapy, p < 0.001; group B: 38.9 +/- 12.9 units before and 58.2 +/- 13.5 units after therapy, p < 0.001). A trend towards faster resolving of pruritus in group B (group A: 5.44 +/- 2.6 scores before and 3.22 +/- 2.31 scores after therapy, p = 0.001; group B: 5.87 +/- 2.79 scores before and 2.24 +/- 1.59 scores after therapy, p < 0.001) was also observed. In group B, the improvement was maintained for couple of weeks after treatment discontinuation, while in group A recurrence of the disease was noted (EASI at day 42 in group A vs. group B: 5.29 +/- 5.6 vs. 1.25 +/- 1.4, p = 0.01). Similar results were also observed for xerosis (p < 0.001) and pruritus (p = 0.002). Concomitant usage of emollients significantly improves xerosis and pruritus during corticosteroid treatment of atopic dermatitis and enables to maintain clinical improvement after therapy discontinuation.

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · randomised controlled trial · 67 citationsread the source →

A randomized controlled evaluation of an online chronic pain self management program.

Internet-based educational and therapeutic programs (e-health applications) are becoming increasingly popular for a variety of psychological and physical disorders. We tested the efficacy of an online Chronic Pain Management Program, a comprehensive, fully self-directed and self-paced system that integrates social networking features and self-management tools into an interactive learning environment. Of 305 adult participants (196 women, 109 men), a total of 162 individuals with chronic pain were randomly assigned unsupervised access to the program for approximately 6 weeks; 143 were assigned to the wait-listed control group with treatment as usual. A comprehensive assessment was administered before the study and approximately 7 and 14 weeks thereafter. All recruitment, data collection, and participant involvement took place online. Participation was fully self-paced, permitting the evaluation of program effectiveness under real-world conditions. Intent-to-treat analysis that used linear growth models was used as the primary analytic tool. Results indicated that program utilization was associated with significant decreases in pain severity, pain-related interference and emotional burden, perceived disability, catastrophizing, and pain-induced fear. Further, program use led to significant declines in depression, anxiety, and stress. Finally, as compared to the wait-listed control group, the experimental group displayed a significant increase in knowledge about the principles of chronic pain and its management. Study limitations are considered, including the recognition that not all persons with chronic pain are necessarily good candidates for self-initiated, self-paced, interactive learning.

Pain · randomised controlled trial · 108 citationsread the source →

Maintenance cognitive stimulation therapy for dementia: single-blind, multicentre, pragmatic randomised controlled trial.

Background: There is good evidence for the benefits of short-term cognitive stimulation therapy for dementia but little is known about possible long-term effects. Aims: To evaluate the effectiveness of maintenance cognitive stimulation therapy (CST) for people with dementia in a single-blind, pragmatic randomised controlled trial including a substudy with participants taking acetylcholinesterase inhibitors (AChEIs). Method: The participants were 236 people with dementia from 9 care homes and 9 community services. Prior to randomisation all participants received the 7-week, 14-session CST programme. The intervention group received the weekly maintenance CST group programme for 24 weeks. The control group received usual care. Primary outcomes were cognition and quality of life (clinical trial registration: ISRCTN26286067). Results: For the intervention group at the 6-month primary end-point there were significant benefits for self-rated quality of life (Quality of Life in Alzheimer's Disease (QoL-AD) P = 0.03). At 3 months there were improvements for proxy-rated quality of life (QoL-AD P = 0.01, Dementia Quality of Life scale (DEMQOL) P = 0.03) and activities of daily living (P = 0.04). The intervention subgroup taking AChEIs showed cognitive benefits (on the Mini-Mental State Examination) at 3 (P = 0.03) and 6 months (P = 0.03). Conclusions: Continuing CST improves quality of life; and improves cognition for those taking AChEIs.

The British journal of psychiatry : the journal of mental science · randomised controlled trial · 104 citationsread the source →

Community Treatment of Posttraumatic Stress Disorder for Children Exposed to Intimate Partner Violence

OBJECTIVE: To evaluate community-provided trauma-focused cognitive behavior therapy (TF-CBT) compared with usual community treatment for children with intimate partner violence (IPV)-related posttraumatic stress disorder (PTSD) symptoms. DESIGN: Randomized controlled trial conducted using blinded evaluators. SETTING: Recruitment, screening, and treatment were conducted at a community IPV center between September 1, 2004, and June 30, 2009. PARTICIPANTS: Of 140 consecutively referred 7- to 14-year-old children, 124 participated. INTERVENTIONS: Children and mothers were randomly assigned to receive 8 sessions of TF-CBT or usual care (child-centered therapy). MAIN OUTCOME MEASURES: Total child PTSD symptoms assessed using child and parent structured interview (Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime Version [K-SADS-PL]) and self-report (University of California at Los Angeles PTSD Reaction Index [RI]). Secondary child outcomes were scores on the K-SADS-PL (PTSD symptom clusters), Screen for Child Anxiety Related Emotional Disorders (SCARED) (anxiety), Children's Depression Inventory (depression), Kaufman Brief Intelligence Test (cognitive functioning), and Child Behavior Checklist (total behavior problems). RESULTS: Intent-to-treat analysis using last observation carried forward showed superior outcomes for TF-CBT on the total K-SADS-PL (mean difference, 1.63; 95% confidence interval [CI], 0.44-2.82), RI (mean difference, 5.5; 95% CI, 1.37-9.63), K-SADS-PL hyperarousal (mean difference, 0.71; 95% CI, 0.22-1.20), K-SADS-PL avoidance (0.55; 0.07-1.03), and SCARED (mean difference, 5.13; 95% CI, 1.31-8.96). Multiple imputation analyses confirmed most of these findings. The TF-CBT completers experienced significantly greater PTSD diagnostic remission (χ(2) = 4.67, P = .03) and had significantly fewer serious adverse events. CONCLUSIONS: Community TF-CBT effectively improves children's IPV-related PTSD and anxiety. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00183326.

Archives of Pediatrics and Adolescent Medicine · randomised controlled trial · 350 citationsread the source →

Long-term outcomes of childhood sexual abuse: an umbrella review.

Background: Although many meta-analyses have examined the association between childhood sexual abuse and subsequent outcomes, the scope, validity, and quality of this evidence has not been comprehensively assessed. We aimed to systematically review existing meta-analyses on a wide range of long-term psychiatric, psychosocial, and physical health outcomes of childhood sexual abuse, and evaluate the quality of the literature. Methods: In this umbrella review, we searched four databases (PsycINFO, PubMed, Cumulative Index to Nursing and Allied Health Literature, and Global Health) from inception to Dec 31, 2018, to identify meta-analyses of observational studies that examined the association between childhood sexual abuse (before 18 years of age) and long-term consequences (after 18 years). We compared odds ratios (ORs) across different outcomes. We also examined measures of quality, including heterogeneity between studies and evidence for publication bias. This study is registered with PROSPERO, CRD42016049701. Findings: We identified 19 meta-analyses that included 559 primary studies, covering 28 outcomes in 4 089 547 participants. Childhood sexual abuse was associated with 26 of 28 specific outcomes: specifically, six of eight adult psychiatric diagnoses (ORs ranged from 2·2 [95% CI 1·8-2·8] to 3·3 [2·2-4·8]), all studied negative psychosocial outcomes (ORs ranged from 1·2 [1·1-1·4] to 3·4 [2·3-4·8]), and all physical health conditions (ORs ranged from 1·4 [1·3-1·6] to 1·9 [1·4-2·8]). Strongest psychiatric associations with childhood sexual abuse were reported for conversion disorder (OR 3·3 [95% CI 2·2-4·8]), borderline personality disorder (2·9 [2·5-3·3]), anxiety (2·7 [2·5-2·8]), and depression (2·7 [2·4-3·0]). The systematic reviews for two psychiatric outcomes (post-traumatic stress disorder and schizophrenia) and one psychosocial outcome (substance misuse) met high quality standards. Quality was low for meta-analyses on borderline personality disorder and anxiety, and moderate for conversion disorder. Assuming causality, population attributable risk fractions for outcomes ranged from 1·7% (95% CI 0·7-3·3) for unprotected sexual intercourse to 14·4% (8·8-19·9) for conversion disorder. Interpretation: Although childhood sexual abuse was associated with a wide range of psychosocial and health outcomes, systematic reviews on only two psychiatric disorders (post-traumatic stress disorder and schizophrenia) and one psychosocial outcome (substance misuse) were of a high quality. Whether services should prioritise interventions that mitigate developing certain psychiatric disorders following childhood abuse requires further review. Higher-quality meta-analyses for specific outcomes and more empirical studies on the developmental pathways from childhood sexual abuse to later outcomes are necessary. Funding: Wellcome Trust.

The lancet. Psychiatry · systematic review · 459 citationsread the source →

A randomised trial of dialectical behaviour therapy and the conversational model for the treatment of borderline personality disorder with recent suicidal and/or non-suicidal self-injury: An effectiveness study in an Australian public mental health service.

Objectives: Borderline personality disorder is a complex mental disorder that is associated with a high degree of suffering for the individual. Dialectical behaviour therapy has been studied in the largest number of controlled trials for treatment of individuals with borderline personality disorder. The conversational model is a psychodynamic treatment also developed specifically for treatment of borderline personality disorder. We report on the outcomes of a randomised trial comparing dialectical behaviour therapy and conversational model for treatment of borderline personality disorder in a routine clinical setting. Method: Participants had a diagnosis of borderline personality disorder and a minimum of three suicidal and/or non-suicidal self-injurious episodes in the previous 12 months. Consenting individuals were randomised to either dialectical behaviour therapy or conversational model and contracted for 14 months of treatment (n = 162 commenced therapy). Dialectical behaviour therapy involved participants attending weekly individual therapy, weekly group skills training and having access to after-hours phone coaching. Conversational model involved twice weekly individual therapy. Assessments occurred at baseline, mid-treatment (7 months) and post-treatment (14 months). Assessments were conducted by a research assistant blind to treatment condition. Primary outcomes were change in suicidal and non-suicidal self-injurious episodes and severity of depression. We hypothesised that dialectical behaviour therapy would be more effective in reducing suicidal and non-suicidal self-injurious behaviour and that conversational model would be more effective in reducing depression. Results: Both treatments showed significant improvement over time across the 14 months duration of therapy in suicidal and non-suicidal self-injury and depression scores. There were no significant differences between treatment models in reduction of suicidal and non-suicidal self-injury. However, dialectical behaviour therapy was associated with significantly greater reductions in depression scores compared to conversational model. Conclusion: This research adds to the accumulating body of knowledge of psychotherapeutic treatment of borderline personality disorder and supports the use of both dialectical behaviour therapy and conversational model as effective treatments in routine clinical settings, with some additional benefits for dialectical behaviour therapy for persons with co-morbid depression.

The Australian and New Zealand journal of psychiatry · randomised controlled trial · 14 citationsread the source →

Cognitive stimulation therapy in the Italian context: its efficacy in cognitive and non-cognitive measures in older adults with dementia.

Objective: Cognitive stimulation therapy (CST) has been shown to have significant benefits in enhancing cognitive functioning and improving the quality of life of people with mild to moderate dementia. The present study examines the efficacy of the Italian version of the therapy (CST-IT). Methods: Older adults with mild to moderate dementia (n = 39) were randomly assigned to two programs: one group participated in the CST-IT, consisting of 14 sessions (twice a week for 7 weeks) and the active control group took part in alternative general activities. The outcome measures were cognitive functioning (measured by the Mini-Mental State Examination-MMSE-, the Alzheimer's Disease Assessment scale-cognitive subscale, the backward digit span test, and a narrative language test); quality of life (Quality of life--Alzheimer's Disease scale); mood (Cornell scale for depression in dementia and the social and emotional loneliness scale); functional activities in daily living (Disability Assessment for Dementia); and behavior (neuropsychiatric inventory). Results: After the intervention, only the CST-IT group maintained its MMSE score, while the control group displayed deterioration. The CST-IT group also performed better in some of the cognitive measures (Alzheimer's Disease Assessment Scale-Cognitive subscale and narrative language), mood measures (Cornell scale, social and emotional loneliness scale with a decrease in reported loneliness), and the Quality of life--Alzheimer's Disease scale. No other treatment effect was observed. Conclusions: The findings confirm the efficacy, at least in the short term, of the CST in sustaining cognitive functions and perceived quality of life in older adults with dementia in the Italian care setting as well.

International journal of geriatric psychiatry · randomised controlled trial · 54 citationsread the source →

evoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating efficacy, safety, and tolerability of semaglutide in early-stage symptomatic Alzheimer's disease.

Background: Disease-modifying therapies targeting the diverse pathophysiology of Alzheimer's disease (AD), including neuroinflammation, represent potentially important and novel approaches. The glucagon-like peptide-1 receptor agonist semaglutide is approved for the treatment of type 2 diabetes and obesity and has an established safety profile. Semaglutide may have a disease-modifying, neuroprotective effect in AD through multimodal mechanisms including neuroinflammatory, vascular, and other AD-related processes. Large randomized controlled trials are needed to assess the efficacy and safety of semaglutide in early-stage symptomatic AD. Methods: evoke and evoke+ are randomized, double-blind, placebo-controlled phase 3 trials investigating the efficacy, safety, and tolerability of once-daily oral semaglutide versus placebo in early-stage symptomatic AD. Eligible participants were men or women aged 55-85 years with mild cognitive impairment or mild dementia due to AD with confirmed amyloid abnormalities (assessed by positron emission tomography or cerebrospinal fluid [CSF] analysis). After a maximum 12-week screening phase, an anticipated 1840 patients in each trial are randomized (1:1) to semaglutide or placebo for 156 weeks (104-week main treatment phase and 52-week extension). Randomized participants follow an 8-week dose escalation regimen (3 mg [weeks 0-4], 7 mg [weeks 4-8], and 14 mg [weeks 8-156]). The primary endpoint is the semaglutide-placebo difference on change from baseline to week 104 in the Clinical Dementia Rating - Sum of Boxes score. Analyses of plasma biomarkers, collected from all participants, and a CSF sub-study (planned n = 210) will explore semaglutide effects on AD biomarkers and neuroinflammation. Results: Enrollment was undertaken between May 18, 2021, and September 8, 2023. Completion of the trials' main phase is expected in September 2025, and the 52-week extension (in which participants and investigators remain blinded to treatment assignment) will continue to October 2026. Conclusion: evoke and evoke+ are the first large-scale trials to investigate the disease-modifying potential of semaglutide in participants with early-stage symptomatic AD, including exploration of effects on AD biomarkers and neuroinflammation. The trials will provide data on the potential disease-modifying effects of semaglutide and will be important in evaluating its utility in the treatment of early-stage symptomatic AD. Trial registration: Clinicaltrials.gov, NCT04777396 and NCT04777409. Date: 02/03/2021.

Alzheimer's research & therapy · randomised controlled trial · 111 citationsread the source →

A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression.

Context: Existing therapies for bipolar depression have a considerable lag of onset of action. Pharmacological strategies that produce rapid antidepressant effects-for instance, within a few hours or days-would have an enormous impact on patient care and public health. Objective: To determine whether an N-methyl-D-aspartate-receptor antagonist produces rapid antidepressant effects in subjects with bipolar depression. Design: A randomized, placebo-controlled, double-blind, crossover, add-on study conducted from October 2006 to June 2009. Setting: Mood Disorders Research Unit at the National Institute of Mental Health, Bethesda, Maryland. Patients Eighteen subjects with DSM-IV bipolar depression (treatment-resistant). Interventions: Subjects maintained at therapeutic levels of lithium or valproate received an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2 test days 2 weeks apart. The Montgomery-Asberg Depression Rating Scale was used to rate subjects at baseline and at 40, 80, 110, and 230 minutes and on days 1, 2, 3, 7, 10, and 14 postinfusion. Main outcome measures: Change in Montgomery-Asberg Depression Rating Scale primary efficacy measure scores. Results: Within 40 minutes, depressive symptoms significantly improved in subjects receiving ketamine compared with placebo (d = 0.52, 95% confidence interval [CI], 0.28-0.76); this improvement remained significant through day 3. The drug difference effect size was largest at day 2 (d = 0.80, 95% CI, 0.55-1.04). Seventy-one percent of subjects responded to ketamine and 6% responded to placebo at some point during the trial. One subject receiving ketamine and 1 receiving placebo developed manic symptoms. Ketamine was generally well tolerated; the most common adverse effect was dissociative symptoms, only at the 40-minute point. Conclusion: In patients with treatment-resistant bipolar depression, robust and rapid antidepressant effects resulted from a single intravenous dose of an N-methyl-D-aspartate antagonist.

Archives of general psychiatry · randomised controlled trial · 725 citationsread the source →

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

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

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

Brief Mindfulness Practices for Healthcare Providers - A Systematic Literature Review.

Mindfulness practice, where an individual maintains openness, patience, and acceptance while focusing attention on a situation in a nonjudgmental way, can improve symptoms of anxiety, burnout, and depression. The practice is relevant for health care providers; however, the time commitment is a barrier to practice. For this reason, brief mindfulness interventions (eg, ≤ 4 hours) are being introduced. We systematically reviewed the literature from inception to January 2017 about the effects of brief mindfulness interventions on provider well-being and behavior. Studies that tested a brief mindfulness intervention with hospital providers and measured change in well-being (eg, stress) or behavior (eg, tasks of attention or reduction of clinical or diagnostic errors) were selected for narrative synthesis. Fourteen studies met inclusion criteria; 7 were randomized controlled trials. Nine of 14 studies reported positive changes in levels of stress, anxiety, mindfulness, resiliency, and burnout symptoms. No studies found an effect on provider behavior. Brief mindfulness interventions may be effective in improving provider well-being; however, larger studies are needed to assess an impact on clinical care.

The American journal of medicine · systematic review · 116 citationsread the source →

The association of demoralization with mental disorders and suicidal ideation in patients with cancer.

Background: Demoralization refers to a state in which there is a perceived inability to cope, that is associated with a sense of disheartenment and a loss of hope and meaning. This study investigated the co-occurrence versus independence of demoralization with mental disorders and suicidal ideation to evaluate its features as a concept of distress in the context of severe illness. Methods: In a cross-sectional sample of 430 mixed cancer patients, we assessed demoralization with the Demoralization Scale (DS); the 4-week prevalence of mood, anxiety, and adjustment disorders and suicidal ideation with the standardized Composite International Diagnostic Interview-Oncology (CIDI-O); and depressive symptoms with the Patient Health Questionnaire-9 (PHQ-9). We compared the relative risk (RR) for mental disorders associated with demoralization to that associated with self-reported depression. Results: Clinically relevant levels of demoralization were present in 21% of the patients. Demoralization co-occurred with a mood/anxiety disorder in 7%; 14% were demoralized in absence of any mood/anxiety disorder. Demoralization and adjustment disorders co-occurred in 2%. The RR for any mood/anxiety disorder was 4.0 in patients with demoralization (95% confidence interval [CI], 2.5-6.2) and 3.0 in those with depression (95% CI, 1.9-4.6). Demoralization, but not depression, was associated with a significantly increased risk for suicidal ideation after controlling for mental disorders (RR, 2.0; 95% CI, 1.1-3.5). Conclusions: Clinically relevant demoralization frequently occurs independently of a mental disorder in patients with cancer and has a unique contribution to suicidal ideation. Demoralization is a useful concept to identify profiles of psychological distress symptoms amenable to interventions improving psychological well-being in this population. Cancer 2017;123:3394-401. © 2017 American Cancer Society.

Cancer · cohort or longitudinal · 124 citationsread the source →

What are the unmet supportive care needs of people with cancer? A systematic review.

Goals of work: The identification and management of unmet supportive care needs is an essential component of health care for people with cancer. Information about the prevalence of unmet need can inform service planning/redesign. Materials and methods: A systematic review of electronic databases was conducted to determine the prevalence of unmet supportive care needs at difference time points of the cancer experience. Results: Of 94 articles or reports identified, 57 quantified the prevalence of unmet need. Prevalence of unmet need, their trends and predictors were highly variable in all domains at all time points. The most frequently reported unmet needs were those in the activities of daily living domain (1-73%), followed by psychological (12-85%), information (6-93%), psychosocial (1-89%) and physical (7-89%). Needs within the spiritual (14-51%), communication (2-57%) and sexuality (33-63%) domains were least frequently investigated. Unmet needs appear to be highest and most varied during treatment, however a greater number of individuals were likely to express unmet need post-treatment compared to any other time. Tumour-specific unmet needs were difficult to distinguish. Variations in the classification of unmet need, differences in reporting methods and the diverse samples from which patients were drawn inhibit comparisons of studies. Conclusion: The diversity of methods used in studies hinders analysis of patterns and predictors of unmet need among people with cancer and precludes generalisation. Well-designed, context-specific, prospective studies, using validated instruments and standard methods of analysis and reporting, are needed to benefit future interventional research to identify how best to address the unmet supportive care needs of people with cancer.

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · systematic review · 641 citationsread the source →

Targeted smoking cessation for dual users of combustible and electronic cigarettes: a randomised controlled trial.

Background: Although many smokers use electronic cigarettes (e-cigarettes) to quit smoking, most continue to smoke while vaping. This dual use might delay cessation and increase toxicant exposure. We aimed to test the efficacy of a self-help intervention designed to help dual users to quit smoking. Methods: In this three-arm randomised controlled trial we recruited individuals in the USA using Facebook and multimedia advertisements. Included participants were 18 years or older, smoked at least weekly in the preceding year, and vaped at least weekly in the preceding month. We used computer generated randomisation with balanced-permuted blocks (block size 10, with 2-4-4 ratio) to allocate participants to assessment only (ASSESS group), generic smoking cessation self-help booklets (GENERIC group), or booklets targeting dual users (eTARGET group). Individuals in the generic or targeted intervention groups received monthly cessation materials for 18 months, with assessments every 3 months for 24 months. The main outcome was self-reported 7-day point-prevalence smoking abstinence at each assessment point. All randomly allocated participants were included in primary analyses using generalised estimating equations for each of 20 datasets created by multiple imputation. Analysis of the χ2s produced an F test. The trial is registered with ClinicalTrials.gov, NCT02416011, and is now closed. Findings: Between July 12, 2016, and June 30, 2017, we randomly assigned 2896 dual users (575 to assessment, 1154 to generic intervention, and 1167 to targeted self-help). 7-day point-prevalence smoking abstinence increased from 14% at 3 months to 42% at 24 months (F7,541·7=67·1, p<0·0001) in the overall sample. Targeted self-help resulted in higher smoking abstinence than did assessment alone throughout the treatment period (F1,973·8=10·20, p=0·0014 [α=0·017]). The generic intervention group had abstinence rates between those of the assessment and targeted groups, but did not significantly differ from either when adjusted for multiple comparisons (GENERIC vs eTARGET F1,1102·5=1·79, p=0·18 [α=0·05]; GENERIC vs ASSESS F1,676·7=4·29, p=0·039 [α=0·025]). Differences between study groups attenuated after the interventions ended. Interpretation: A targeted self-help intervention with high potential for dissemination could be efficacious in promoting smoking cessation among dual users of combustible cigarettes and e-cigarettes. Funding: National Institute on Drug Abuse, National Cancer Institute.

The Lancet. Public health · randomised controlled trial · 45 citationsread the source →

Family-centered advance care planning for teens with cancer.

Importance: Advance care planning (ACP) prepares patients and their families for future health care decisions; however, the needs of adolescent oncology patients for participation in ACP have not been well studied. Objective: To examine the efficacy of family-centered ACP. Design and setting: Two-group randomized controlled trial in a pediatric oncology program. Participants: Sixty adolescents aged 14 to 21 years with cancer and their surrogates or families were enrolled in the study between January 17, 2011, and March 29, 2012. Intervention: Thirty dyads received 3- to 60-minute sessions 1 week apart. Intervention dyads completed (1) the Lyon Family-Centered ACP Survey, (2) the Respecting Choices interview, and (3) Five Wishes. Control subjects received standard care plus information. Main outcome measures: Statement of treatment preferences and Decisional Conflict Scale score. Results: The mean age of the adolescents was 16 years; 36 (60%) were male, 30 (50%) white, 26 (43%) black, and 4 (7%) Asian. Diagnoses were as follows: leukemia (14 patients [47%]), brain tumor (8 [27%]), solid tumor (6 [20%]), and lymphoma (2 [7%]). Significantly increased congruence was observed for intervention dyads compared with controls for 4 of the 6 disease-specific scenarios; for example, for situation 2 ("treatment would extend my life by not more than 2 to 3 months"), intervention dyads demonstrated higher congruence (κ = 0.660; P < .001) vs control dyads (κ = -0.0636; P = .70). Intervention adolescents (100%) wanted their families to do what is best at the time, whereas fewer control adolescents (62%) gave families this leeway. Intervention adolescents were significantly better informed about end-of-life decisions (t = 2.93; effect size, 0.961; 95% CI, 0.742-1.180; P = .007). Intervention families were more likely to concur on limiting treatments than controls. An ethnic difference was found in only one situation. Conclusions: Advance care planning enabled families to understand and honor their adolescents' wishes. Intervention dyads were more likely than controls to limit treatments. Underserved African American families were willing to participate.

JAMA pediatrics · randomised controlled trial · 149 citationsread the source →

Asthma as a barrier to children's physical activity: implications for body mass index and mental health.

Objectives: The purpose of this work was to identify barriers to physical activity in children with asthma and to compare their customary activity levels, BMI and emotional well-being with that of children with other medical conditions. It was hypothesized that children with asthma would have higher BMI and lower levels of customary activity. Patients and methods: We studied children aged 7 to 14 years attending hospital outpatient clinics for either asthma (asthma group: n = 56) or for otorhinolaryngology or dermatological conditions (nonasthma group: n = 61). In this cross-sectional survey, children's weight and height were recorded and their BMI classified according to International Obesity Task Force classification of obesity. Child mental health was assessed by the parent-rated Strengths and Difficulties Questionnaire. The child-rated Physical Activity Questionnaire assessed total sedentary and physical activities during the previous 24 hours. Results: The asthma group had a higher mean BMI (20.78 vs 18.82) and higher rates of obesity (21.4% vs 6.6%). Children with asthma reported fewer physical activities than the nonasthma group (median 4 per day vs 6 per day) but comparable levels of sedentary activities. Asthma was the strongest predictor of lower activity scores, followed by younger age. The asthma group had higher levels of emotional difficulties and, within this group, more active children had better mental health. More parents in the asthma group identified the child's health as a barrier to exercise (60.7% vs 11%). The same was true of children (66.1% vs 11.5%). Conclusions: We found that children attending a hospital clinic for asthma were more likely to be obese and were significantly less active than a comparison group with other medical conditions. Asthma was identified as a barrier to exercise by parents and children. Strategies to promote exercise within pediatric asthma care are needed to protect both mental and physical health.

Pediatrics · cohort or longitudinal · 117 citationsread the source →

When adolescents stop psychological therapy: Rupture-repair in the therapeutic alliance and association with therapy ending.

The therapeutic alliance predicts dropout from psychological therapy, and ruptures in the therapeutic alliance may also predict dropout, yet there is a dearth of research with adolescents. This study investigated whether markers of rupture-repair in the alliance were indicative of different types of treatment ending in adolescents receiving psychological treatment for depression. Data were from the IMPACT study, a trial investigating the effectiveness of therapies for adolescent depression. Participants were randomly allocated to receive a brief psychosocial intervention, cognitive-behavioral therapy, or short-term psychoanalytic psychotherapy. The sample (N = 35) comprised adolescents who had either completed their treatment (n = 14) or dropped out (n = 21) according to their therapist. Dropout cases were further classified as dissatisfied (n = 14) or got-what-they-needed (n = 7) based on posttherapy interviews with the adolescent and therapist. Selected recordings of therapy sessions were rated using the Rupture Resolution Rating System and Working Alliance Inventory (observer version). Therapeutic alliance and rupture-repair during therapy were similar for completers and got-what-they-needed dropouts, whereas dissatisfied dropouts had poorer therapeutic alliance, more ruptures, ruptures that were frequently unresolved, and greater therapist contribution to ruptures. Qualitative analysis of sessions led to the construction of three categories of therapist contribution to ruptures: therapist minimal response, persisting with a therapeutic activity, and focus on risk. Results suggest that ruptures, especially when unresolved, could be warning signs of disengagement and dropout from therapy. Future research should investigate how ruptures may be effectively identified and resolved in treatment with adolescents. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Psychotherapy (Chicago, Ill.) · randomised controlled trial · 33 citationsread the source →

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

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

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

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 →

Barriers and facilitators to screening and treating malnutrition in older adults living in the community: a mixed-methods synthesis.

Background: Malnutrition (specifically undernutrition) in older, community-dwelling adults reduces well-being and predisposes to disease. Implementation of screen-and-treat policies could help to systematically detect and treat at-risk and malnourished patients. We aimed to identify barriers and facilitators to implementing malnutrition screen and treat policies in primary/community care, which barriers have been addressed and which facilitators have been successfully incorporated in existing interventions. Method: A data-base search was conducted using MEDLINE, Embase, PsycINFO, DARE, CINAHL, Cochrane Central and Cochrane Database of Systematic Reviews from 2012 to June 2016 to identify relevant qualitative and quantitative literature from primary/community care. Studies were included if participants were older, community-dwelling adults (65+) or healthcare professionals who would screen and treat such patients. Barriers and facilitators were extracted and mapped onto intervention features to determine whether these had addressed barriers. Results: Of a total of 2182 studies identified, 21 were included (6 qualitative, 12 quantitative and 3 mixed; 14 studies targeting patients and 7 targeting healthcare professionals). Facilitators addressing a wide range of barriers were identified, yet few interventions addressed psychosocial barriers to screen-and-treat policies for patients, such as loneliness and reluctance to be screened, or healthcare professionals' reservations about prescribing oral nutritional supplements. Conclusion: The studies reviewed identified several barriers and facilitators and addressed some of these in intervention design, although a prominent gap appeared to be psychosocial barriers. No single included study addressed all barriers or made use of all facilitators, although this appears to be possible. Interventions aiming to implement screen-and-treat approaches to malnutrition in primary care should consider barriers that both patients and healthcare professionals may face. Review registrations: PROSPERO: CRD42017071398 . The review protocol was registered retrospectively.

BMC family practice · review · 50 citationsread the source →

Interoception in Psychiatric Disorders: A Review of Randomized, Controlled Trials with Interoception-Based Interventions.

Interoception, or the process of sensing, interpreting, and integrating internal bodily signals, has increasingly been the subject of scientific research over the past decade but is still not well known in clinical practice. The aim of this article is to review clinical treatment interventions that use interoception, to synthesize the current research knowledge, and to identify the gaps where future research is needed. We conducted a comprehensive literature search on randomized, controlled trials that both include interoception in treatment interventions for individuals with psychiatric disorders and measure aspects of interoception using self-report measures. Out of 14 randomized, controlled trials identified, 7 found that interventions with interoception were effective in ameliorating symptoms. These studies included individuals with anxiety disorders, eating disorders, psychosomatic disorders, and addictive disorders. All of the intervention studies with positive clinical outcomes also demonstrated changes on interoceptive measures; however, these measures were often related to specific illness symptoms. Interoception may be a mechanism of action in improving clinical symptomatology, though studies incorporating general, symptom-independent interoceptive measures remain scarce. To further our understanding of the role interoception has in psychiatric disorders and their treatment, more studies integrating interoceptive measures are needed, along with a clearer definition of interoceptive terms used.

Harvard review of psychiatry · review · 89 citationsread the source →

A preliminary investigation of neural correlates of treatment in adolescents with generalized anxiety disorder.

Objective: Generalized anxiety disorder (GAD) is a prevalent and debilitating psychiatric condition of adolescence. Two effective forms of treatment are cognitive behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs). This pilot study examined changes in brain function following each type of treatment in GAD. Method: Subjects were 14 youths with GAD (7 had CBT, 7 received fluoxetine) and 10 age- and gender-matched healthy peers. Functional magnetic resonance imaging (fMRI) scans were acquired before and after treatment for patients and over two comparable time points for controls. During fMRI acquisition, a probe detection task with emotional (angry, happy) and neutral faces allowed for assessment of neural response to threat. Following previous research, region of interest analyses were performed in the right ventrolateral prefrontal cortex (VLPFC). Results: fMRI results showed increased right VLPFC activation, relative to controls, in the medication (t(15) = 3.01, p < 0.01) and CBT (t(15) = 3.22, p < 0.01) groups following treatment. Conclusions: This study shows significant increase in right VLPFC activation in response to angry faces following treatment with CBT or fluoxetine for GAD. This is consistent with previous research indicating that the VLPFC may facilitate effective responding to underlying neural correlates of anxiety in other brain regions, such as the amygdala.

Journal of child and adolescent psychopharmacology · 84 citationsread the source →

Effect of a cash transfer programme for schooling on prevalence of HIV and herpes simplex type 2 in Malawi: a cluster randomised trial.

Background: Lack of education and an economic dependence on men are often suggested as important risk factors for HIV infection in women. We assessed the efficacy of a cash transfer programme to reduce the risk of sexually transmitted infections in young women. Methods: In this cluster randomised trial, never-married women aged 13-22 years were recruited from 176 enumeration areas in the Zomba district of Malawi and randomly assigned with computer-generated random numbers by enumeration area (1:1) to receive cash payments (intervention group) or nothing (control group). Intervention enumeration areas were further randomly assigned with computer-generated random numbers to conditional (school attendance required to receive payment) and unconditional (no requirements to receive payment) groups. Participants in both intervention groups were randomly assigned by a lottery to receive monthly payments ranging from US$1 to $5, while their parents were independently assigned with computer-generated random numbers to receive $4-10. Behavioural risk assessments were done at baseline and 12 months; serology was tested at 18 months. Participants were not masked to treatment status but counsellors doing the serologic testing were. The primary outcomes were prevalence of HIV and herpes simplex virus 2 (HSV-2) at 18 months and were assessed by intention-to-treat analyses. The trial is registered, number NCT01333826. Findings: 88 enumeration areas were assigned to receive the intervention and 88 as controls. For the 1289 individuals enrolled in school at baseline with complete interview and biomarker data, weighted HIV prevalence at 18 month follow-up was 1·2% (seven of 490 participants) in the combined intervention group versus 3·0% (17 of 799 participants) in the control group (adjusted odds ratio [OR] 0·36, 95% CI 0·14-0·91); weighted HSV-2 prevalence was 0·7% (five of 488 participants) versus 3·0% (27 of 796 participants; adjusted OR 0·24, 0·09-0·65). In the intervention group, we noted no difference between conditional versus unconditional intervention groups for weighted HIV prevalence (3/235 [1%] vs 4/255 [2%]) or weighted HSV-2 prevalence (4/233 [1%] vs 1/255 [<1%]). For individuals who had already dropped out of school at baseline, we detected no significant difference between intervention and control groups for weighted HIV prevalence (23/210 [10%] vs 17/207 [8%]) or weighted HSV-2 prevalence (17/211 [8%] vs 17/208 [8%]). Interpretation: Cash transfer programmes can reduce HIV and HSV-2 infections in adolescent schoolgirls in low-income settings. Structural interventions that do not directly target sexual behaviour change can be important components of HIV prevention strategies. Funding: Global Development Network, Bill & Melinda Gates Foundation, National Bureau of Economic Research Africa Project, World Bank's Research Support Budget, and several World Bank trust funds (Gender Action Plan, Knowledge for Change Program, and Spanish Impact Evaluation fund).

Lancet (London, England) · randomised controlled trial · 389 citationsread the source →

The Management of Preoperative Anxiety in Children: An Update

Anxiety in children undergoing surgery is characterized by subjective feelings of tension, apprehension, nervousness, and worry that may be expressed in various forms (1). Postoperative maladaptive behaviors, such as new onset enuresis, feeding difficulties, apathy and withdrawal, and sleep disturbances, may also result from anxiety before surgery. In fact, studies have indicated that up to 60% of all children undergoing surgery may present with negative behavioral changes at 2 wk postoperatively (1,2). Variables such as age, temperament, and anxiety of the child and parent in the preoperative holding area have been identified as predictors for these behavioral changes (1). Extreme anxiety during induction of anesthesia is also associated with an increase of these postoperative negative behavioral changes (3). In addition to behavioral manifestations, preoperative anxiety activates the human stress response, leading to increased serum cortisol, epinephrine, and natural killer cell activity (4,5). This stress response can be activated by many different noxious stimuli including fear, anxiety, pain, cold, major surgery, and infection. The main components of the stress system are the corticotropin-releasing hormone and the locus ceruleus-norepinephrine/autonomic systems and their peripheral effectors, the hypothalamic pituitary-adrenal axis and the limbs of the autonomic system (5). There is also evidence for a bidirectional communication between the neuroendocrine system and the immune system. Stress activates the hypothalamic pituitary-adrenal axis, increases circulating glucocorticoids, and is associated with alterations of immune function and susceptibility to infection and neoplastic disease (6). The human response to surgical stress is characterized by a series of hormonal, immunological, and metabolic changes that together constitute the global surgical stress response (7,8). This perioperative response is considered a homeostatic mechanism for adapting to the perioperative injury. The effects of the surgical stress response, however, may be detrimental: neuroendocrine hormones (e.g., cortisol, catecholamines) and cytokines (e.g., interleukin-6) provoke a negative nitrogen balance and catabolism, delay wound healing, and cause postoperative immunosuppression (7,8). Children are particularly vulnerable to the global surgical stress response because of limited energy reserves, larger brain masses, and obligatory glucose requirements (9). Because acute psychological stress, such as preoperative anxiety, is associated with immediate stress hormone release, the contribution of perioperative psychological factors to the global perioperative stress response cannot be ignored. In adults, increased preoperative anxiety is associated with poor postoperative behavioral and clinical recovery (10,11). As an indicator of the importance of preoperative anxiety, a panel of 72 anesthesiologists recently ranked various anesthesia low-morbidity clinical outcomes based on importance and frequency. The five clinical outcomes with the highest combined score were incisional pain, nausea, vomiting, preoperative anxiety, and discomfort from IV insertion (12). Thus, consensus is evident among anesthesiologists about the need to treat anxiety before surgery. In a modern epidemiological framework, diseases can be characterized in terms of risk factors, interventions, and outcomes. In this update, we will review preoperative anxiety in children using this conceptual framework (Fig. 1).Figure 1: Conceptual framework of perioperative anxiety. Revised from (72).The Psychobiology of Separation Learning to cope with separation from a parent is necessary for a child’s normal development (13). Separation experiences such as going to school facilitate normal psychological development and personality organization. Other separation experiences, such as perioperative separation, may precipitate confusion and anxiety. Between these two extremes, there are many separation experiences with varying degrees of psychobiological stress. In the first weeks of life, infants are able to discriminate among people, but will accept care and comfort from adults other than their parents (14). By 3 mo of age, however, infants begin to respond differently to familiar and unfamiliar people. Older infants smile more at familiar people and may even try to engage their attention (14). Separation anxiety usually begins at 7–8 mo of age and peaks around 1 yr of age. In part, separation anxiety represents the infant’s acquisition of new cognitive abilities and object permanence. The intensity of separation anxiety declines with age, largely because of increasing cognitive abilities and memory capacity. Frequently, however, the increase in abilities does not immunize toddlers and preschoolers against the stress and distress of separations. The extent to which separation is traumatic or evokes adaptive responses reflects an individual child’s developmental age, parenting experiences, genetic endowment, and environmental stability. For children with biologically based vulnerabilities, such as a sensitivity to novelty and transitions, even expected separations may impose a greater degree of stress than for less sensitive children (13). How parents help the child mediate a separation experience play a crucial role in the child’s acute and long-term responses. In the extreme, the parent may be unable to mediate the experience for the child because of limitations such as severe anxiety. How well children have been cared for up to the time of the separation also influences their response to the stressor. Children deprived of attention in the home are at increased risk for stress in response to separations. Thus, the extent to which separations evoke adaptive responses reflects an individual child’s genetics, personality, parenting, and previous life experiences. Preoperative Anxiety: Identification Identifying risk factors for development of preoperative anxiety is important, as more resources can be directed toward vulnerable children. Children 1–5 yr old are at the highest risk for developing extreme anxiety (1). This is not surprising considering the psychobiology of separation anxiety. Children who are shy or inhibited and those who have a high intelligence quotient and lack good adaptive abilities are also at increased risk (15). Previous surgery or hospitalization and poor response to visits to the pediatrician’s office are also predictors for the development of preoperative anxiety. Finally, parental anxiety has been identified as a predictor for increased child’s anxiety. Preoperative Anxiety: Behavioral Modalities Preoperative Preparation Programs Most studies suggest that preoperative preparation programs reduce anxiety and enhance coping in children (16). These behavioral preparation programs have evolved significantly over recent decades. In the 1960s, preparation programs were designed to provide an orientation tour and narrative information and facilitate trust between the hospital staff, the child, and the parent (16). In the 1970s, modeling techniques were developed where children indirectly experienced the perioperative course by role rehearsal using dolls or by viewing a video (17). These modeling techniques were augmented in the late 1980s with child life preparation and the teaching of coping skills (17). Currently, development of coping skills is considered the most effective preoperative preparation intervention, followed by modeling, play therapy, operating room tour, and printed material (18). Although experts favor teaching of coping skills, most preparation programs in the United States consist of an orientation tour and printed information (18). Although coping preparation has been associated with reduction of anxiety in the preoperative holding area, no differences were found among the various preparation programs during induction, in the recovery room period, or postoperatively (19). Thus, the cost-effectiveness of child life specialists may or may not be justified by an associated reduction in preoperative anxiety. Psychological preparation programs should be tailored to individual needs such as age, developmental stage, and previous experience (20). The priority of the age criterion relates to both the anxiety such exposure might generate and the length of time over which children can cope with anticipation. In addition, timing of the program before surgery is an important variable (20). Children aged ≥6 yr benefit most if they participate in a preparation program ≥5 days before surgery and benefit least if the program is given only 1 day before surgery. This phenomenon is related to the way that children in this age group process new information. Finally, a child who has previously undergone surgery or has been hospitalized may develop an exaggerated emotional response to an information-based preparation program (20). As increased parental anxiety results in increased child’s anxiety (1), there is a need for interventions that are designed specifically for parents. Cassady et al. (21) demonstrated that parental preoperative anxiety decreased after viewing an educational videotape. We suggest that more parental interventions need to be developed and that a child’s anxiety should be evaluated as an outcome. Preoperative Anxiety: Behavioral Modalities Parental Presence during Induction of Anesthesia. Parents and children prefer to stay together during medical procedures such as immunizations, dental treatment, and induction of anesthesia (22). Some data indicate, however, that parental presence during induction of anesthesia (PPIA) is allowed in 26% of US hospitals and is encouraged in only 8% of hospitals (23). In contrast, 28% of hospitals have no formal hospital policy and parental presence is against hospital policy for 32% of hospitals in the US. The smallest use of this induction technique was reported in the South-Central region and the highest in the Northwest and the Northeast (23). Interestingly, anesthesiologists from Great Britain (GB) encourage PPIA significantly more than anesthesiologists from the US (23,24). The reasons for these differences may include the use of different induction techniques, less concern about legal ramifications in GB, and a stronger demand for parental presence in GB. Economic issues such as operating room (OR) efficiency, infrastructure issues, lack of induction rooms and patchy preoperative educational programs, probably limit the availability of PPIA in the US. Potential benefits from PPIA include reducing the need for preoperative sedatives and avoiding the fear and anxiety that may occur on separation to the OR. Other benefits, such as increasing the child’s compliance during induction, remain controversial. Objections to PPIA include concern about disruption of the OR routine, crowded ORs, and a possible adverse reaction of parents. In addition, increased parental anxiety can increase a child’s anxiety, prolong anesthetic induction, and place additional stress on the anesthesiologist. Although early observational studies suggested reduced anxiety if parents were present during induction (25), more recent randomized controlled trials indicate that routine parental presence is not beneficial (26–28). One study demonstrated that only children >4 yr of age, those who have a “calm” baseline personality, or those who have a parent with a “calm” baseline personality benefit from this intervention (26). When interpreting the results of these studies, however, it should be noted that the design of a randomized controlled study does not reflect the practice of all anesthesiologists. When data of survey studies are reviewed (23,24), it is noticed that most anesthesiologists use either PPIA or sedative premedication to treat preoperative anxiety. When sedative premedications were directly compared with PPIA, however, it was found that children receiving oral midazolam were significantly less anxious and more compliant during the induction process (27). A recent study examined whether a combination of PPIA and oral midazolam is more effective than oral midazolam alone (28). The investigators found that PPIA has no additive anxiolytic effects for children who received oral midazolam preoperatively. Parents who accompany their sedated children into the ORs, however, are significantly less anxious and more satisfied both with the separation process and with the overall anesthetic, nursing and surgical care provided (28). PPIA is also associated with important legal implications. Lewyn (29) described a case in which a mother was invited to accompany her son into an emergency treatment room. According to the court, the mother fainted and suffered an injury to the head. In its verdict the Illinois Supreme Court stated that a hospital, which allows a nonpatient to accompany a patient during treatment, does not have a duty to protect the nonpatient from fainting. However, if medical personnel invite the nonpatient to participate in the treatment, then the hospital has a legal responsibility toward the nonpatient. Interestingly, some hospitals in the US now require the parents to sign a written informed consent acknowledging the risk of being present during induction of anesthesia. We believe that future research interests should shift towards an emphasis on what parents actually do during induction of anesthesia, rather than simply on their presence. Allowing a parent into an OR without significant preparation may be counterproductive because some parent behaviors, such as criticism and commands, are associated with increased distress. Effective methods of training such as parental preparation programs can be developed for enhancing the effects of PPIA. Preoperative Anxiety: Pharmacological Modalities The reported rate of use of pharmacological modalities for the treatment of preoperative anxiety in the US varies widely among age groups and geographical locations (24). Premedicant sedative drugs are least often used with children <3 yr of age and most often used with adults <65 yr of age (25% vs 75%). Currently, the most commonly used sedative premedicant in the preoperative holding area is midazolam (85%), followed by ketamine (4%), transmucosal fentanyl (3%), and meperidine (2%) (Fig. 2). TABLETABLE The majority of children in the US are premedicated via the oral route (80%), followed by the intranasal route (8%), the IM route (6%), and the rectal route (3%).Figure 2: Types of premedicants used in the preoperative holding area (23).Table 1: Premedications Administered by the Oral RouteTable 2: Premedications Administered Transmucosally and RectallyMidazolam. Midazolam is a short-acting benzodiazepine that is very lipophilic at physiologic pH, which accounts for its rapid onset of action. Davis et al. (30) has demonstrated that intranasally administered midazolam in a dosage of 0.2–0.3 mg/kg in patients undergoing myringotomies led to satisfactory separation from parents and a satisfactory induction over 70% of the time and did not prolong recovery time and hospital discharge time. Midazolam administered intranasally is effective in reducing anxiety in children within 10–12 min (31). A major drawback of intranasally administered midazolam, however, is that at least 50% of children cry on administration because it transiently irritates the nasal passages. Midazolam can also be given as a nasal spray, which is effective in reducing procedural anxiety in children undergoing cancer therapy (32). Midazolam can be administrated sublingually at the same dosage as intranasally. Although sublingual administration of midazolam is associated with a decreased incidence of crying (18%), it may be difficult to prevent small children from either swallowing the midazolam or spitting it out immediately (33). Rectal administration of midazolam in doses of 0.5–1.0 mg/kg effectively reduces the anxiety of children before induction of anesthesia (34). Although the incidence of hiccups after IV midazolam is <2%, the incidence noted that in a recent study involving rectally administered midazolam was more than 20%(34). The investigators had no explanation as to the increased rate of hiccups other than the young age of the children, but they found that the hiccups were easily treated by ethyl chloride nasal spray (34). Orally administered midazolam (0.5 mg/kg) has been shown to significantly reduce preoperative anxiety in young children (27,28). Orally administered midazolam can be given in a dosage of 0.25 mg to 1.0 mg/kg up to total dose of 20 mg depending on the of surgery and the anxiety of the A and and midazolam in a of 2 in et al. examined different doses of the midazolam and found that 0.25 mg/kg in satisfactory and in a majority of patients within 20 This study also found that increasing the dose in an increase in the of patients with satisfactory and a time to onset of Other that the time for premedicated children from their parents is min with a sedative between 20 and min The of administered midazolam and in the discharge of patients is controversial. Although recent studies noted that administrated midazolam is not associated with a discharge two studies involving children undergoing that and recovery are in the children who oral midazolam study involving children who myringotomies using or anesthesia indicated that children who were given oral midazolam experienced significant in recovery time but no in discharge time from the hospital Finally, et al. have the of a combination of preoperative oral midazolam and The investigators found that requirements by and discharge was in children who had been given midazolam preoperatively. The investigators suggested that the increased postoperative may have been to of and midazolam on As indicated a significant of children experiences maladaptive behavioral changes after surgery (1). In children who were premedicated with oral midazolam had a significantly decreased incidence of negative behavioral changes during the first after surgery However, this study noted that by 2 wk postoperatively there were no significant differences between the midazolam and The mechanism by which midazolam the incidence of postoperative behavioral changes is not but it may be related to of the perioperative process Children who received a benzodiazepine for dental and were about the experience dental than children who were not about their dental This may be particularly important for children undergoing surgical in children after oral midazolam as early as min and anxiolytic effects are as early as min after administration This timing to onset of is of importance in surgery where the of is very Midazolam and can be with which The dose in children is mg/kg given IV in a of up to 1.0 mg Some children who are with will experience it is to for can also be intranasally in a dose of given by from a is a that is very which the a good for administration and Oral transmucosal fentanyl administered in the of a to a and as the was the first sedative by the and in for use in children. Oral transmucosal in and dosage is in a and given to children in the dosage of for sedative is often associated with which usually min after children begin to the children before induction of anesthesia does however, to decreased or with induction in young children In a small of can cause a leading to significant a in be present this is administered in children is associated with a incidence of postoperative and that is not easily by In fact, at least study was because of a very incidence of preoperative A significant of is that it the postoperative et al. reported that preoperative is as effective as IV fentanyl given for of postoperative in children undergoing is an that a of and from the of ketamine compared with other premedicants is that it less given in sedative doses A of ketamine as compared with other premedicants is the of increased and which can to can also cause and in children, which can parents if they are not informed about this increased incidence of postoperative is associated with preoperative administration of ketamine The effects are all dose related and can be with the use of a small dose of administered ketamine mg/kg) the time of onset of the of administered ketamine is also dose related with administered ketamine mg/kg) an onset of of min and ketamine leading to within 20 min administration may be associated with and during the postoperative recent studies have found that use of a benzodiazepine given to children undergoing ketamine did not the incidence of In addition, the incidence of postoperative and is no different in children receiving midazolam, or a combination of ketamine and midazolam together The IV preparation of ketamine can be with or to an oral of which is by most children. can be also be given intranasally rectally and IM mg/kg) care discharge time of children who received administered ketamine is reported not to be compared with administered midazolam provided that of surgery is than min administered IM in an emergency room however, was found to significantly delay discharge and increase compared with midazolam administered rectally or intranasally et al. reported that the combination of midazolam and ketamine administrated had a rate of satisfactory compared with with either oral was also found to be to IM and in children undergoing The provided and and there was less need for IV as compared with the IM is an first developed as an but found to have and sedative Orally administrated in a dose of anesthetic and for postoperative requirements by 50% in children premedicated with This in may be to the of as well as a administered is also as effective as administered fentanyl for postoperative in children undergoing The recovery of children who is to the recovery of children who oral but significantly less postoperative as compared with One major drawback for the use of as a sedative premedicant is its onset of action. has to be administered as early as min before surgery In children, is at min for administered and min for rectally administered for the research should on the development of sedatives that will be well have a very time for onset of and have of action. In addition, developed preoperative sedatives should such as and should anesthetic requirements and reduce postoperative Finally, new methods of sedative premedications should also be For of should be as well as oral transmucosal methods for other than usually at least 1 for effective serum of drugs to be is can significantly the of a and has been effective in fentanyl in adults within min at 2 Finally, the of treatment modalities such as should be research is in these The to for review of this

Anesthesia & Analgesia · review · 408 citationsread the source →

Leadership Development in Postgraduate Medical Education: A Systematic Review of the Literature.

Purpose: To evaluate and interpret evidence relevant to leadership curricula in postgraduate medical education (PGME) to better understand leadership development in residency training. Method: The authors conducted a systematic review of peer-reviewed, English-language articles from four databases published between 1980 and May 2, 2017 that describe specific interventions aimed at leadership development. They characterized the educational setting, curricular format, learner level, instructor type, pedagogical methods, conceptual leadership framework (including intervention domain), and evaluation outcomes. They used Kirkpatrick effectiveness scores and Best Evidence in Medical Education (BEME) Quality of Evidence scores to assess the quality of the interventions. Results: Twenty-one articles met inclusion criteria. The classroom setting was the most common educational setting (described in 17 articles). Most curricula (described in 13 articles) were isolated, with all curricula ranging from three hours to five years. The most common instructor type was clinical faculty (13 articles). The most commonly used pedagogical method was small group/discussion, followed by didactic teaching (described in, respectively, 15 and 14 articles). Study authors evaluated both pre/post surveys of participant perceptions (n = 7) and just postintervention surveys (n = 10). The average Kirkpatrick Effectiveness score was 1.0. The average BEME Quality of Evidence score was 2. Conclusions: The results revealed that interventions for developing leadership during PGME lack grounding conceptual leadership frameworks, provide poor evaluation outcomes, and focus primarily on cognitive leadership domains. Medical educators should design future leadership interventions grounded in established conceptual frameworks and pursue a comprehensive approach that includes character development and emotional intelligence.

Academic medicine : journal of the Association of American Medical Colleges · systematic review · 67 citationsread the source →

Selective serotonin reuptake inhibitors for premenstrual syndrome.

Background: Premenstrual syndrome (PMS) is a common cause of physical, psychological and social problems in women of reproductive age. The key characteristic of PMS is the timing of symptoms, which occur only during the two weeks leading up to menstruation (the luteal phase of the menstrual cycle). Selective serotonin reuptake inhibitors (SSRIs) are increasingly used as first line therapy for PMS. SSRIs can be taken either in the luteal phase or else continuously (every day). SSRIs are generally considered to be effective for reducing premenstrual symptoms but they can cause adverse effects. Objectives: The objective of this review was to evaluate the effectiveness and safety of SSRIs for treating premenstrual syndrome. Search methods: Electronic searches for relevant randomised controlled trials (RCTs) were undertaken in the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, PsycINFO, and CINAHL (February 2013). Where insufficient data were presented in a report, attempts were made to contact the original authors for further details. Selection criteria: Studies were considered in which women with a prospective diagnosis of PMS, PMDD or late luteal phase dysphoric disorder (LPDD) were randomised to receive SSRIs or placebo for the treatment of premenstrual syndrome. Data collection and analysis: Two review authors independently selected the studies, assessed eligible studies for risk of bias, and extracted data on premenstrual symptoms and adverse effects. Studies were pooled using random-effects models. Standardised mean differences (SMDs) with 95% confidence intervals (CIs) were calculated for premenstrual symptom scores, using separate analyses for different types of continuous data (that is end scores and change scores). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for dichotomous outcomes. Analyses were stratified by type of drug administration (luteal or continuous) and by drug dose (low, medium, or high). We calculated the number of women who would need to be taking a moderate dose of SSRI in order to cause one additional adverse event (number needed to harm: NNH). The overall quality of the evidence for the main findings was assessed using the GRADE working group methods. Main results: Thirty-one RCTs were included in the review. They compared fluoxetine, paroxetine, sertraline, escitalopram and citalopram versus placebo. SSRIs reduced overall self-rated symptoms significantly more effectively than placebo. The effect size was moderate when studies reporting end scores were pooled (for moderate dose SSRIs: SMD -0.65, 95% CI -0.46 to -0.84, nine studies, 1276 women; moderate heterogeneity (I(2) = 58%), low quality evidence). The effect size was small when studies reporting change scores were pooled (for moderate dose SSRIs: SMD -0.36, 95% CI -0.20 to -0.51, four studies, 657 women; low heterogeneity (I(2)=29%), moderate quality evidence).SSRIs were effective for symptom relief whether taken only in the luteal phase or continuously, with no clear evidence of a difference in effectiveness between these modes of administration. However, few studies directly compared luteal and continuous regimens and more evidence is needed on this question. Withdrawals due to adverse effects were significantly more likely to occur in the SSRI group (moderate dose: OR 2.55, 95% CI 1.84 to 3.53, 15 studies, 2447 women; no heterogeneity (I(2) = 0%), moderate quality evidence). The most common side effects associated with a moderate dose of SSRIs were nausea (NNH = 7), asthenia or decreased energy (NNH = 9), somnolence (NNH = 13), fatigue (NNH = 14), decreased libido (NNH = 14) and sweating (NNH = 14). In secondary analyses, SSRIs were effective for treating specific types of symptoms (that is psychological, physical and functional symptoms, and irritability). Adverse effects were dose-related. The overall quality of the evidence was low to moderate, the main weakness in the included studies being poor reporting of methods. Heterogeneity was low or absent for most outcomes, though (as noted above) there was moderate heterogeneity for one of the primary analyses. Authors' conclusions: SSRIs are effective in reducing the symptoms of PMS, whether taken in the luteal phase only or continuously. Adverse effects are relatively frequent, the most common being nausea and asthenia. Adverse effects are dose-dependent.

The Cochrane database of systematic reviews · meta-analysis · 118 citationsread the source →

"I don't want my marriage to end": a qualitative investigation of the sociocultural factors influencing contraceptive use among married Rohingya women residing in refugee camps in Bangladesh.

Background: The timely provision of comprehensive contraceptive services to Rohingya women is impeded due to a lack of clarity and understanding of their traditional beliefs and cultural frameworks. Recognizing this challenge, our paper aims to explore the socio-cultural factors influencing the utilization of contraceptives among married Rohingya women living in the refugee camps of Cox's Bazar, Bangladesh. Method: A qualitative study was conducted in two unregistered Rohingya camps (Camp 7&14) located in Ukhiya Upazila, Cox's Bazar from January 10th to 20th, 2022. A total of 14 In-Depth Interviews (IDIs) were conducted among married Rohingya women of reproductive age (15-49 years), along with 16 Key Informant Interviews (KIIs) involving stakeholders engaged in reproductive healthcare provision. Participants were selected using purposive sampling. All interviews were conducted in the local language, recorded, transcribed verbatim, and subsequently translated into English. The data were analyzed using NVivo (Version 11), and the analysis process followed Neuman's three-phase coding system. Results: Five broad themes were identified: Sociocultural expectations and values attached to births, power imbalances within marital relationships, the role of religious beliefs, fear of side effects, and misperceptions about contraception. Having a larger number of children is viewed positively as it is believed that children play a crucial role in preserving the lineage and contributing to the growth of the Islamic population. Despite expressing an inclination towards contraception, the disapproval of husbands becomes a significant barrier for women. Defying their husbands' wishes can result in instances of Intimate Partner Violence (IPV) and even marriage dissolution within the camps. Moreover, the fear of side effects, such as a particular method would cause infertility, discourages women from using contraception. Many of these fears stem from myths, misconceptions, and mistrust in the existing medical system. Conclusion: Addressing the socio-cultural barriers that prevent women from using modern contraception will have important public health implications. These findings can support in crafting culturally sensitive programs and educational interventions. These initiatives can assist Rohingya refugee women in planning their pregnancies and reducing high-risk pregnancies, ultimately leading to a decrease in maternal mortality rates within the community.

Reproductive health · 4 citationsread the source →

Evaluation of Frequency of Encounters With Primary Care Physicians vs Visits to Community Pharmacies Among Medicare Beneficiaries.

Importance: The shift toward value-based care has placed emphasis on preventive care and chronic disease management services delivered by multidisciplinary health care teams. Community pharmacists are particularly well positioned to deliver these services due to their accessibility. Objective: To compare the number of patient visits to community pharmacies and the number of encounters with primary care physicians among Medicare beneficiaries who actively access health care services. Design, setting, and participants: This cross-sectional study analyzed a 5% random sample of 2016 Medicare beneficiaries from January 1, 2016, to December 31, 2016 (N = 2 794 078). Data were analyzed from October 23, 2019, to December 20, 2019. Medicare Part D beneficiaries who were continuously enrolled and had at least 1 pharmacy claim and 1 encounter with a primary care physician were included in the final analysis (n = 681 456). Those excluded from the study were patients who were not continuously enrolled in Part D until death, those with Part B skilled nursing claims, and those with Part D mail-order pharmacy claims. Exposures: We conducted analyses for the overall sample and for subgroups defined by demographics, region of residence, and clinical characteristics. Main outcomes and measures: Outcomes included the number of visits to community pharmacies and encounters with primary care physicians. Unique visits to the community pharmacy were defined using a 13-day window between individual prescription drug claims. Kruskal-Wallis tests were used to compare the medians for the 2 outcomes. Results: A total of 681 456 patients (mean [SD] age, 72.0 [12.5] years; 418 685 [61.4%] women and 262 771 [38.6%] men) were included in the analysis; 82.2% were white, 9.6% were black, 2.4% were Hispanic, and 5.7% were other races/ethnicities. Visits to the community pharmacy outnumbered encounters with primary care physicians (median [interquartile range (IQR)], 13 [9-17] vs 7 [4-14]; P < .001). The number of pharmacy visits was significantly larger than the number of primary care physician encounters for all subgroups evaluated except for those with acute myocardial infarction (median [IQR], 15 [12-19] vs 14 [7-26]; P = .60 using a 13-day window). The difference in the number of pharmacy and primary care physician encounters was larger in rural areas (median [IQR], 14 [10-17] vs 5 [2-11]; P < .001) than in metropolitan areas (median [IQR], 13 [8-17] vs 8 [4-14]; P < .001). In all 50 states and in all but 9 counties, the number of community pharmacy visits was larger than the number of encounters with primary care physicians. Conclusions and relevance: This cross-sectional study suggests that community pharmacists are accessible health care professionals with frequent opportunities to interact with community-dwelling patients. Primary care physicians should work collaboratively with community pharmacists, who can assist in the delivery of preventive care and chronic disease management.

JAMA network open · 150 citationsread the source →

Toll-Like Receptor 4/MyD88-Mediated Signaling of Hepcidin Expression Causing Brain Iron Accumulation, Oxidative Injury, and Cognitive Impairment After Intracerebral Hemorrhage.

Background: Disturbance of brain iron metabolism after intracerebral hemorrhage (ICH) results in oxidative brain injury and cognition impairment. Hepcidin plays an important role in regulating iron metabolism, and we have reported that serum hepcidin is positively correlated with poor outcomes in patients with ICH. However, the roles of hepcidin in brain iron metabolism after ICH remain largely unknown. Methods: Parabiosis and ICH models combined with in vivo and in vitro experiments were used to investigate the roles of hepcidin in brain iron metabolism after ICH. Results: Increased hepcidin-25 was found in serum and primarily in astrocytes after ICH. The brain iron efflux, oxidative brain injury, and cognition impairment were improved in Hepc-/- ICH mice but aggravated by the human hepcidin-25 peptide in C57BL/6 ICH mice. Data obtained in in vitro studies showed that increased hepcidin inhibited the intracellular iron efflux of brain microvascular endothelial cells but was rescued by a hepcidin antagonist, fursultiamine. Using parabiosis ICH models also shows that increased serum hepcidin prevents brain iron efflux. In addition, Toll-like receptor 4 (TLR4)/MyD88 signaling pathway increased hepcidin expression by promoting interleukin-6 expression and signal transducer and activator of transcription 3 phosphorylation. TLR4-/- and MyD88-/- mice exhibited improvement in brain iron efflux at 7, 14, and 28 days after ICH, and the TLR4 antagonist (6R)-6-[N-(2-chloro-4-fluorophenyl) sulfamoyl] cyclohex-1-ene-1-carboxylate significantly decreased brain iron levels at days 14 and 28 after ICH and improved cognition impairment at day 28. Conclusions: The results presented here show that increased hepcidin expression caused by inflammation prevents brain iron efflux via inhibition of the intracellular iron efflux of brain microvascular endothelial cells entering into circulation and aggravating oxidative brain injury and cognition impairment, which identifies a mechanistic target for muting inflammation to promote brain iron efflux and to attenuate oxidative brain injury after ICH.

Circulation · 119 citationsread the source →

Effects of DMT on mental health outcomes in healthy volunteers.

Psilocybin, a serotonergic psychedelic, is being increasingly researched in clinical studies for the treatment of psychiatric disorders. The relatively lengthy duration of oral psilocybin's acute effects (4-6 h) may have pragmatic and cost-effectiveness limitations. Here, we explored the effects of intravenous (IV) N,N-Dimethyltryptamine (DMT), a closely related, but faster-acting psychedelic intervention, on mental health outcomes in healthy volunteers. Data is reported from two separate analyses: (1) A comparison of mental health-related variables 1 week after 7, 14, 18, and 20 mg of IV DMT versus IV saline placebo (n = 13) and, (2) A prospective dataset assessing effects before versus 2 weeks after 20 mg of IV DMT (n = 17). Mental health outcomes included measures of depression severity (QIDS-SR16), trait anxiety (STAI-T), Neuroticism (NEO-FFI), wellbeing (WHO-5), meaning in life (MLQ), optimism (LOT-R), and gratitude (GQ-6). In both the prospective and placebo-controlled datasets, significant improvements in scores of depression were found 1-2 weeks after DMT administration. Significant reductions in trait Neuroticism were only found for the placebo-controlled sample. Finally, changes in depression and trait anxiety correlated with acute peak experiences (assessed via 'Oceanic Boundlessness'). While the use of two separate cohorts in pooled analysis limits the generalizability of these correlational findings, these results suggest that DMT may reduce depressive symptomatology by inducing peak experiences. The short half-life of IV DMT and its potential for flexible dosing via controlled infusions makes it an appealing candidate for psychedelic medicine. Further research in clinical samples is needed to corroborate the therapeutic potential of DMT.

Scientific reports · 26 citationsread the source →

Black Cumin (Nigella sativa L.) Seed Press Cake as a Novel Material for the Development of New Non-Dairy Beverage Fermented with Kefir Grains.

In recent years, there has been a growing interest from the food industry in new products that are increasingly desired by consumers because of the functional ingredients they contain. This category certainly includes fermented plant-based beverages, which combine the properties of plant substrates with the beneficial effects of fermentation on human health. In our study, two trial variants containing 20% and 30% black cumin (Nigella sativa L.) seed press cake (BCPC) were inoculated with kefir grain cultures and then incubated at 25 °C for 24 h. The resulting beverages were stored under refrigeration (6 °C) for 28 days. During storage, pH, total free amino acids, reducing sugars, changes in the microbial population, viscosity, textural parameters, and color were measured on days 1, 5, 7, 14, 21, and 28. Throughout the storage period, the number of lactic acid bacteria, as well as yeasts, exceeded the recommended minimum level. Numerous changes in product parameters were observed in the tested beverages as a result of fermentation compared to non-fermented products. This study indicates the possibility of using BCPC as a valuable matrix for the production of a functional kefir-like beverage.

Microorganisms · 8 citationsread the source →

Heat stress-induced memory impairment is associated with neuroinflammation in mice.

Background: Heat stress induces many pathophysiological responses and has a profound impact on brain structure. It has been demonstrated that exposure to high temperature induces cognitive impairment in experimental animals and humans. Although the effects of heat stress have long been studied, the mechanisms by which heat stress affects brain structure and cognition not well understood. Methods: In our longitudinal study of mice exposed to heat over 7, 14, or 42 days, we found that heat stress time dependently impaired cognitive function as determined by Y-maze, passive avoidance, and novel object recognition tests. To elucidate the histological mechanism by which thermal stress inhibited cognitive abilities, we examined heat stress-induced inflammation in the hippocampus. Results: In mice subjected to heat exposure, we found: 1) an increased number of glial fibrillary acid protein (GFAP)- and macrophage-1 antigen (Mac-1)-positive cells, 2) up-regulated nuclear factor (NF)-κB, a master regulator of inflammation, and 3) marked increases in cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and cytokine interleukin (IL)-1β and tumor necrosis factor (TNF)-α in the mouse hippocampus. We also observed that neuronal and synaptic densities were degenerated significantly in hippocampal regions after heat exposure, as determined by histological analysis of neuronal nuclei (NeuN), postsynaptic density protein 95 (PSD-95), and synaptophysin expression. Moreover, in heat-exposed mice, we found that the number of cells positive for doublecortin (DCX), a marker of neurogenesis, was significantly decreased compared with control mice. Finally, anti-inflammatory agent minocycline inhibited the heat stress-induced cognitive deficits and astogliosis in mice. Conclusions: Together, these findings suggest that heat stress can lead to activation of glial cells and induction of inflammatory molecules in the hippocampus, which may act as causative factors for memory loss, neuronal death, and impaired adult neurogenesis.

Journal of neuroinflammation · 117 citationsread the source →

Usability, Acceptability, Feasibility, and Effectiveness of a Gamified Mobile Health Intervention (Triumf) for Pediatric Patients: Qualitative Study.

Background: Mental disorders are notably prevalent in children with chronic illnesses, whereas a lack of access to psychological support might lead to potential mental health problems or disruptions in treatment. Digitally delivered psychological interventions have shown promising results as a supportive treatment measure for improving health outcomes during chronic illness. Objective: This study aimed to evaluate the usability, acceptability, and feasibility of providing psychological and treatment support in a clinical setting via a mobile game environment. In addition, the study aimed to evaluate the preliminary effectiveness of the mobile health game. Methods: Patients aged 7 to 14 years with less than a year from their diagnosis were eligible to participate in the study. In total, 15 patients were invited to participate by their doctor. A total of 9 patients (age range: 7-12 years; mean age 9.1 years) completed the 60-day-long study in which the Triumf mobile health game was delivered as a digital intervention. In an engaging game environment, patients were offered psychological and treatment support, cognitive challenges, and disease-specific information. The fully digital intervention was followed by a qualitative interview conducted by a trained psychologist. The results of the interview were analyzed in conjunction with patient specific in-game qualitative data. Ethical approval was obtained to conduct the study. Results: Patients positively perceived the game, resulting in high usability and acceptability evaluations. Participants unanimously described the game as easy to use and engaging in terms of gamified activities, while also providing beneficial and trustworthy information. Furthermore, the overall positive evaluation was emphasized by an observed tendency to carry on gaming post study culmination (67%, 10/15). Psychological support and mini games were the most often used components of the game, simultaneously the participants also highlighted the education module as one of the most preferred. On average, the patients sought and received psychological support or education on 66.6 occasions during the 60-day intervention. Participants spent the most time collecting items from the city environment (on average 15.6 days, SD 8.1), indicative of exploratory behavior, based on the quantitative in-game collected data. During the intervention period, we observed a statistically significant decrease in general health problems (P=.003) and saw a trend toward a decrease in depression and anxiety symptoms. Conclusions: This study demonstrated that a game environment could be a promising medium for delivering comprehensive supportive care to pediatric patients with cancer alongside standard treatment, with potential application across a variety of chronic conditions. Importantly, the results indicate that the study protocol was feasible with modifications to randomized controlled trials, and the game could be considered applicable in a clinical context. By giving an empirical evaluation of delivering psychological support via the game environment, our work stands to inform future mobile health interventions.

JMIR serious games · 26 citationsread the source →

Burden of 375 diseases and injuries, risk-attributable burden of 88 risk factors, and healthy life expectancy in 204 countries and territories, including 660 subnational locations, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023.

Background: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. Methods: The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. Findings: Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant). Interpretation: Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. Funding: Gates Foundation and Bloomberg Philanthropies.

Lancet (London, England) · 257 citationsread the source →

The association between breastfeeding, the stress response, inflammation, and postpartum depression during the postpartum period: Prospective cohort study.

Background: Research suggests that exclusive breastfeeding may have a stress-protective role in postpartum depression; however, less is known about the underlying mechanisms by which this protection may occur or whether the protective relationship holds for women who mix breast and bottle feeding. Objectives: To examine patterns of the stress response, inflammation, and depressive symptoms among women predominantly breastfeeding or bottle feeding their infants at 6 months postpartum. Design: A part of a larger longitudinal study across 6 months postpartum investigating the psychoneuroimmunology (PNI) of postpartum depression. Setting: Prenatal clinics and community. Participants: One hundred nineteen postpartum women who met inclusion/exclusion criteria and followed up from the prenatal period to postpartum 6 months. Methods: Data were collected during seven home visits occurring during the 3rd trimester (weeks 32-36) and on postpartum days 7 and 14, months 1, 2, 3, and 6. Women completed stress and depression surveys and provided blood for pro- (IL-1β, IL-6, IL-8, TNF-a, IFN-γ) and anti-inflammatory (IL-10) cytokines, and collected saliva for diurnal cortisol. Results: Self-report of predominant breastfeeding during 6 months postpartum ranged from 91.9% at day 7 to 70.6% at month 6 postpartum. There were no associations between the pattern of feeding and depressive symptoms. Biological differences, however, existed between the groups, with levels of salivary cortisol at 8 AM and 8:30 AM at month 6 higher and levels of IL-6 at month 6 lower in women who primarily breastfed compared to those who primarily bottle fed their infants after controlling for confounding variables. Conclusions: Breastfeeding was not related to postpartum depression however differences in stress and inflammatory markers are apparent at month 6 postpartum.

International journal of nursing studies · 40 citationsread the source →

Motivational processes in mild cognitive impairment and Alzheimer's disease: results from the Motivational Reserve in Alzheimer's (MoReA) study.

Background: Brain reserve, i.e., the ability of the brain to tolerate age- and disease-related changes in a way that cognitive function is still maintained, is assumed to be based on the lifelong training of various abilities. The Motivational Reserve in Alzheimer's (MoReA) is a longitudinal study that aims to examine motivational processes as a protective factor in mild Alzheimer's dementia (AD) and mild cognitive impairment (MCI). This paper presents the results of motivational variables, frequency of diagnoses, and prediction of global cognition as well as depression in a one-year longitudinal study. Methods: The sample consists of 64 subjects with MCI and 47 subjects with mild AD at baseline. At baseline, the physical/neurological examinations, standard clinical assessment, neuropsychological testing, and assessment of motivational variables were performed. At follow-up (FU) one year later, neuropsychological testing including cognition, functional abilities, behavioral and affective symptoms, and global clinical assessments of severity have been repeated. Results: AD cases have lower motivational capacities as measured with a midlife motivation-related occupational score and informant-reported present motivational processes, but do not differ with regard to delay of gratification (DoG) and self-reported motivational processes. DoG and delay discounting (DD) were relatively stable during the measurement interval. However, 20 % of the MCI cases converted to mild AD at FU, and 17 % of the mild AD cases converted to moderate AD. The rate of depression of Alzheimer's disease was 9 at baseline and 21 % at FU, and the rate of apathy was 7 and 14 %, respectively. Global cognition at FU was mainly predicted by baseline global cognition but also by one of the motivational variables (scenario test). Depression at FU was predicted mainly by two motivational variables (self-reported and informant-reported motivational processes). Conclusions: This research might inform motivation-related strategies for prevention and early intervention with older people or people at risk for AD.

BMC psychiatry · 23 citationsread the source →

The Psychological Distress of Food Insecurity: A Qualitative Study of the Emotional Experiences of Parents and Their Coping Strategies.

Background: Food insecurity increases the risks of diet-related chronic disease and mental health outcomes in low-income adults; however, the pathways underlying these associations have not been clearly identified. Chronic, psychological distress may represent an important pathway between food insecurity and health. Objective: To identify types of psychological distress, experiential descriptions, and the array of emotional responses and coping strategies specific to food insecurity among parents with children DESIGN: A phenomenological qualitative study using one-on-one, in-depth interviews. Participants and setting: Forty-eight adults (parents) were recruited from the San Francisco Bay Area in 2016-17. Eligibility criteria included any experience of household food insecurity over the past 12 months, having a child aged 7 to 14 years, and both parent and child with the ability to speak English fluently. Statistical analyses: Data were analyzed using the constant comparative method to reveal emergent themes across multiple interviews. Results: Parents discussed six themes related to the psychological distress of food insecurity: stress from the logistical and financial balancing act of feeding one's family, frustration and lack of choice associated with the high costs of healthy foods, stigma of using community resources, shame of not being able to provide for one's family, sadness about their cyclical and chronic food situation, and guilt over their inability to adequately provide for their children. Coping responses included negative responses, such as sleeping and drinking to avoid thinking about food insecurity, and positive responses of relying on their friends and family for support, staying hopeful, and spending time with their children. Conclusions: The commonality of emotional responses stemming from the experience of food insecurity can increase the risk for clinical anxiety and depression. Future development of interventions and policies to alleviate food insecurity must include social support and adequate safety systems.

Journal of the Academy of Nutrition and Dietetics · 39 citationsread the source →

Use of rumination and activity monitoring for the identification of dairy cows with health disorders: Part I. Metabolic and digestive disorders.

The objectives of this study were to evaluate (1) the performance of an automated health-monitoring system (AHMS) to identify cows with metabolic and digestive disorders-including displaced abomasum, ketosis, and indigestion-based on an alert system (health index score, HIS) that combines rumination time and physical activity; (2) the number of days between the first HIS alert and clinical diagnosis (CD) of the disorders by farm personnel; and (3) the daily rumination time, physical activity, and HIS patterns around CD. Holstein cattle (n=1,121; 451 nulliparous and 670 multiparous) were fitted with a neck-mounted electronic rumination and activity monitoring tag (HR Tags, SCR Dairy, Netanya, Israel) from at least -21 to 80 d in milk (DIM). Raw data collected in 2-h periods were summarized per 24 h as daily rumination and activity. A HIS (0 to 100 arbitrary units) was calculated daily for individual cows with an algorithm that used rumination and activity. A positive HIS outcome was defined as a HIS of <86 during at least 1 d from -5 to 2 d after CD. Blood concentrations of nonesterified fatty acids, β-hydroxybutyrate, total calcium, and haptoglobin were determined in a subgroup of cows (n=459) at -11±3, -4±3, 0, 3±1, 7±1, 14±1, and 28±1 DIM. The sensitivity of the HIS was 98% [95% confidence interval (CI): 93, 100] for displaced abomasum (n=41); 91% (95% CI: 83, 99) for ketosis (n=54); 89% (95% CI: 68, 100) for indigestion (n=9); and 93% (95% CI: 89, 98) for all metabolic and digestive disorders combined (n=104). Days (mean and 95% CI) from the first positive HIS <86 and CD were -3 (-3.7, -2.3), -1.6 (-2.3, -1.0), -0.5 (-1.5, 0.5), and -2.1 (-2.5, -1.6) for displaced abomasum, ketosis, indigestion, and all metabolic and digestive disorders, respectively. The patterns of rumination, activity, and HIS for cows flagged by the AHMS were characterized by lower levels than for cows without a health disorder and cows not flagged by the AHMS from -5 to 5 d after CD, depending on the disorder and parameter. Differences between cows without health disorders and those flagged by the AHMS for blood markers of metabolic and health status confirmed the observations of the CD and AHMS alerts. The overall sensitivity and timing of the AHMS alerts for cows with metabolic and digestive disorders indicated that AHMS that combine rumination and activity could be a useful tool for identifying cows with metabolic and digestive disorders.

Journal of dairy science · 106 citationsread the source →

Long-term health outcomes after exposure to repeated concussion in elite level: rugby union players.

Background: There is continuing concern about effects of concussion in athletes, including risk of the neurodegenerative disease chronic traumatic encephalopathy. However, information on long-term health and wellbeing in former athletes is limited. Method: Outcome after exposure to repeated brain injury was investigated in 52 retired male Scottish international rugby players (RIRP) and 29 male controls who were similar in age and social deprivation. Assessment included history of playing rugby and traumatic brain injury, general and mental health, life stress, concussion symptoms, cognitive function, disability and markers of chronic stress (allostatic load). Results: The estimated number of concussions in RIRP averaged 14 (median=7; IQR 5-40). Performance was poorer in RIRP than controls on a test of verbal learning (p=0.022) and of fine co-ordination of the dominant hand (p=0.038) and not significantly different on other cognitive tests (p>0.05). There were no significant associations between number of concussions and performance on cognitive tests. Other than a higher incidence of cardiovascular disease in controls, no group differences were detected in general or mental health or estimates of allostatic load. In RIRP, persisting symptoms attributed to concussion were more common if reporting more than nine concussions (p=0.028), although these symptoms were not perceived to affect social or work functioning. Conclusions: Despite a high number of concussions in RIRP, differences in mental health, social or work functioning were not found late after injury. Subtle group differences were detected on two cognitive tests, the cause of which is uncertain. Prospective group comparison studies on representative cohorts are required.

Journal of neurology, neurosurgery, and psychiatry · 77 citationsread the source →

[Mental health survey of medical staff in a tertiary infectious disease hospital for COVID-19].

Objective: To investigate the mental health of clinical first-line medical staff in COVID-19 epidemic and provide theoretical basis for psychological intervention. Methods: The mental health status of the first-line medical staff was investigated by Self-rating Anxiety Scale(SAS) and Post-Traumatic Stress Disorder Self- rating Scale (PTSD-SS). From February 7 to 14, 2020, 246 medical staff participated in the treatment of COVID-19 were investigated using cluster sampling, and received 230 responses, with a recovery rate of 93.5%. Results: The incidence of anxiety in medical staff was 23.04% (53/230) , and the score of SAS was(42.91±10.89). Among them, the incidence of severe anxiety, moderate anxiety and mild anxiety were 2.17%(5/230) , 4.78%(11/230) and 16.09%(37/230) , respectively. The incidence of anxiety in female medical staff was higher than that in male [25.67%(48/187) vs 11.63%(5/43) , Z=-2.008, P=0.045], the score of SAS in female medical staff was higher than that in male [(43.78±11.12) vs (39.14±9.01) , t=-2.548, P=0.012]. The incidence of anxiety in nurses was higher than that in doctors[26.88% (43/160) vs 14.29% (10/70) , Z=-2.066, P=0.039], and the score of SAS in nurses was higher than that in doctors [ (44.84±10.42) vs (38.50±10.72) , t=-4.207, P<0.001]. The incidence of stress disorder in medical staff was 27.39% (63/230) , and the score of PTSD-SS was (42.92±17.88) . The score of PTSD-SS in female medical staff was higher than that in male[ (44.30±18.42) vs (36.91±13.95) , t=-2.472, P=0.014]. Conclusion: In COVID-19 epidemic , the incidence of anxiety and stress disorder is high among medical staff. Medical institutions should strengthen the training of psychological skills of medical staff. Special attention should be paid to the mental health of female nurses.

Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases · 358 citationsread the source →

Effectiveness of cash-plus programmes on early childhood outcomes compared to cash transfers alone: A systematic review and meta-analysis in low- and middle-income countries.

Background: To strengthen the impact of cash transfers, these interventions have begun to be packaged as cash-plus programmes, combining cash with additional transfers, interventions, or services. The intervention's complementary ("plus") components aim to improve cash transfer effectiveness by targeting mediating outcomes or the availability of supplies or services. This study examined whether cash-plus interventions for infants and children <5 are more effective than cash alone in improving health and well-being. Methods and findings: Forty-two databases, donor agencies, grey literature sources, and trial registries were systematically searched, yielding 5,097 unique articles (as of 06 April 2021). Randomised and quasi-experimental studies were eligible for inclusion if the intervention package aimed to improve outcomes for children <5 in low- and middle-income countries (LMICs) and combined a cash transfer with an intervention targeted to Sustainable Development Goal (SDG) 2 (No Hunger), SDG3 (Good Health and Well-being), SDG4 (Education), or SDG16 (Violence Prevention), had at least one group receiving cash-only, examined outcomes related to child-focused SDGs, and was published in English. Risk of bias was appraised using Cochrane Risk of Bias and ROBINS-I Tools. Random effects meta-analyses were conducted for a cash-plus intervention category when there were at least 3 trials with the same outcome. The review was preregistered with PROSPERO (CRD42018108017). Seventeen studies were included in the review and 11 meta-analysed. Most interventions operated during the first 1,000 days of the child's life and were conducted in communities facing high rates of poverty and often, food insecurity. Evidence was found for 10 LMICs, where most researchers used randomised, longitudinal study designs (n = 14). Five intervention categories were identified, combining cash with nutrition behaviour change communication (BCC, n = 7), food transfers (n = 3), primary healthcare (n = 2), psychosocial stimulation (n = 7), and child protection (n = 4) interventions. Comparing cash-plus to cash alone, meta-analysis results suggest Cash + Food Transfers are more effective in improving height-for-age (d = 0.08 SD (0.03, 0.14), p = 0.02) with significantly reduced odds of stunting (OR = 0.82 (0.74, 0.92), p = 0.01), but had no added impact in improving weight-for-height (d = -0.13 (-0.42, 0.16), p = 0.24) or weight-for-age z-scores (d = -0.06 (-0.28, 0.15), p = 0.43). There was no added impact above cash alone from Cash + Nutrition BCC on anthropometrics; Cash + Psychosocial Stimulation on cognitive development; or Cash + Child Protection on parental use of violent discipline or exclusive positive parenting. Narrative synthesis evidence suggests that compared to cash alone, Cash + Primary Healthcare may have greater impacts in reducing mortality and Cash + Food Transfers in preventing acute malnutrition in crisis contexts. The main limitations of this review are the few numbers of studies that compared cash-plus interventions against cash alone and the potentially high heterogeneity between study findings. Conclusions: In this study, we observed that few cash-plus combinations were more effective than cash transfers alone. Cash combined with food transfers and primary healthcare show the greatest signs of added effectiveness. More research is needed on when and how cash-plus combinations are more effective than cash alone, and work in this field must ensure that these interventions improve outcomes among the most vulnerable children.

PLoS medicine · meta-analysis · 40 citationsread the source →

Adverse event profile and associated factors following surgical voluntary medical male circumcision in two regions of Namibia, 2015-2018.

Introduction: Monitoring clinical safety of voluntary medical male circumcision (VMMC) is critical to minimize risk as VMMC programs for HIV prevention are scaled. This cross-sectional analysis describes the adverse event (AE) profile of a large-scale, routine VMMC program and identifies factors associated with the development, severity, and timing of AEs to provide recommendations for program quality improvement. Materials and methods: From 2015-2018 there were 28,990 circumcisions performed in International Training and Education Center for Health (I-TECH) supported regions of Namibia in collaboration with the Ministry of Health and Social Services. Two routine follow-up visits after VMMC were scheduled to identify clients with AEs. Summary statistics were used to describe characteristics of all VMMC clients and the subset who experienced an AE. We used chi-square tests to evaluate associations between AE timing, patient age, and other patient and AE characteristics. We used a logistic regression model to explore associations between patient characteristics and AE severity. Results: Of the 498 clients with AEs (AE rate of 1.7%), 40 (8%) occurred ≤2 days, 262 (53%) occurred 3-7 days, 161 (32%) between day 8 and 14, and 35 (7%) were ≥15 days post-VMMC. Early AEs (on or before day 2) tended to be severe and categorized as bleeding, while infections were the most common AEs occurring later (p<0.001). Younger clients (aged 10-14 years) experienced more infections, whereas older clients experienced more bleeding (p<0.001). Conclusions: Almost 40% of AEs occurred after the second follow-up visit, of which 179 (91%) were infections. Improvements in pre-surgical and post-surgical counselling and post-operative educational materials encouraging clients to seek care at any time, adoption of alternative follow-up methods, and the addition of a third follow-up visit may improve outcomes for patients. Enhancing post-surgical counselling and emphasizing wound care for younger VMMC clients and their caregivers could help mitigate elevated risk of infection.

PloS one · 10 citationsread the source →

Teacher's Emotional Support and Math Performance: The Chain Mediating Effect of Academic Self-Efficacy and Math Behavioral Engagement.

Positive teacher-student interaction can exert a positive influence on student engagement and math performance. As an important part of teacher-student interaction, emotional support of a teacher plays an indispensable role in the math performance of junior middle school and elementary school students. This study aimed to explore the effects of teacher's emotional support on math performance, and examine the mediating role of academic self-efficacy and math behavioral engagement. A total of 1,294 students in grades 3-5 and 7-8 from 14 junior middle and primary schools in China took part in the web-based survey. Results showed the following: (1) academic self-efficacy mediated the relationship between teacher's emotional support and math performance of Chinese primary and middle school boys and girls; math behavioral engagement mediated the relationship between teacher's emotional support and math performance of Chinese primary and middle school boys and girls; (2) The relationship between teacher's emotional support and math performance of Chinese junior middle school boys and girls was mediated by the chain of academic self-efficacy and math behavioral engagement.

Frontiers in psychology · 28 citationsread the source →

Adverse childhood experiences and trajectories of internalizing, externalizing, and prosocial behaviors from childhood to adolescence.

Background: Adverse childhood experiences (ACEs) predict poorer mental health across the life course but most of the extant research has employed ACE scores or individual adversities using retrospective data. Objectives: To study the impact of ACEs on later mental health using not only ACEs scores and individual ACEs, but also latent class analysis (LCA), which respects the clustering of adversities. Participants and setting: 8823 members from the UK Millennium Cohort Study. Methods: We investigated the impact of prospectively reported ACEs on mental health trajectories derived using the Strengths and Difficulties Questionnaire at age 3, 5, 7, 11 and 14. Associations between LCA-derived ACE clusters, ACE scores, individual ACEs and mental health trajectories were tested using linear mixed effects models. Results: With statistical significance set at 5% level, ACE scores showed a graded association with internalizing (ACE score of 1: β = 0.057; ACE score of 2: β = 0.108; ACE score of 3: β = 0.202), externalizing (ACE score of 1: β = 0.142; ACE score of 2: β = 0.299; ACE score of 3: β = 0.415) and prosocial behaviors (ACE score of 1: β=-0.019; ACE score of 2: β=-0.042; ACE score of 3: β=-0.059). Harsh parenting and physical punishment were particularly strongly associated with externalizing (β = 0.270 and β = 0.256) and negatively associated with prosocial behaviors (β=-0.046 and β=-0.058). Parental discord and parental depression showed the strongest associations with internalizing problems (β = 0.125 and β = 0.113). LCA did not discriminate ACE clusters in this dataset. Conclusions: ACEs have an important impact on mental health from childhood to adolescence. ACEs score approach yielded useful results, which were further enhanced by exploring individual ACEs.

Child abuse & neglect · 83 citationsread the source →