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Trace amine-associated receptor 1 (TAAR1) agonists for psychosis: protocol for a living systematic review and meta-analysis of human and non-human studies.
BackgroundThere is an urgent need to develop more effective and safer antipsychotics beyond dopamine 2 receptor antagonists. An emerging and promising approach is TAAR1 agonism. Therefore, we will conduct a living systematic review and meta-analysis to synthesize and triangulate the evidence from preclinical animal experiments and clinical studies on the efficacy, safety, and underlying mechanism of action of TAAR1 agonism for psychosis.MethodsIndependent searches will be conducted in multiple electronic databases to identify clinical and animal experimental studies comparing TAAR1 agonists with licensed antipsychotics or other control conditions in individuals with psychosis or animal models for psychosis, respectively. The primary outcomes will be overall psychotic symptoms and their behavioural proxies in animals. Secondary outcomes will include side effects and neurobiological measures. Two independent reviewers will conduct study selection, data extraction using predefined forms, and risk of bias assessment using suitable tools based on the study design. Ontologies will be developed to facilitate study identification and data extraction. Data from clinical and animal studies will be synthesized separately using random-effects meta-analysis if appropriate, or synthesis without meta-analysis. Study characteristics will be investigated as potential sources of heterogeneity. Confidence in the evidence for each outcome and source of evidence will be evaluated, considering the summary of the association, potential concerns regarding internal and external validity, and reporting biases. When multiple sources of evidence are available for an outcome, an overall conclusion will be drawn in a triangulation meeting involving a multidisciplinary team of experts. We plan trimonthly updates of the review, and any modifications in the protocol will be documented. The review will be co-produced by multiple stakeholders aiming to produce impactful and relevant results and bridge the gap between preclinical and clinical research on psychosis.Protocol registrationPROSPERO-ID: CRD42023451628.
Communication in Primary Healthcare: A State-of-the-Art Literature Review of Conversation-Analytic Research
We report the first state-of-the-art review of conversation-analytic (CA) research on communication in primary healthcare. We conducted a systematic search across multiple bibliographic databases and specialist sources and employed backward and forward citation tracking. We included 177 empirical studies spanning four decades of research and 16 different countries/health systems, with data in 17 languages. The majority of studies originated in United States and United Kingdom and focused on medical visits between physicians and adult patients. We generated three broad research themes in order to synthesize the study findings: managing agendas, managing participation, and managing authority. We characterize the state-of-the-art for each theme, illustrating the progression of the work and making comparisons across different languages and health systems, where possible. We consider practical applications of the findings, reflect on the state of current knowledge, and suggest some directions for future research. Data reported are in multiple languages.
Towards agreement amongst parents, teachers and children on perceived psychopathology in children in a Kenyan socio-cultural context: a cross-sectional study.
BACKGROUND: Our objective was to determine levels of agreement between parents, teachers and children on mental symptoms in the children. Teachers, children and parents constitute the TRIAD in the perception of psychopathology in children. Analyzing the perceptions of psychopathology from the perspectives of parents, teachers, and children is essential for a comprehensive understanding of a child's mental health. METHODS: We identified 195 participants across ten randomly sampled primary schools in South East Kenya. Potential participants were randomly selected and a sampling interval calculated to determine the study participants. The children (Class 5-8; aged 11-14) completed the Youth Self-Report (YSR) scale, the parents the Child Behavior Check List (CBCL) on their children and the teachers completed the Teachers Rating Form (TRF) on the children. Only parents and teachers who gave consent as well as children who gave assent were included in the study. Analysis was conducted using Stata 14.1 and Pearson correlation coefficients used to calculate the correlations between CBCL, YSR and TRF. RESULTS: The children agreed least with the parents and more with the teachers. There was a greater agreement between the children and their teachers in 5 (2 internalizing disorders and 3 externalizing disorders) out of the 8 conditions. Children and parents agreed only on somatic disorders and conduct disorders. YSR mean scores were significantly lower than those for CBCL for all problem scales. Mean scores of TRF and YSR were comparable in the majority of the problems measured. CONCLUSION: We suggest broad-based psychoeducation to include children, parents/guardians and teachers to enhance shared awareness of psychopathology and uptake of treatment and for the consideration of an integrated mental health system.
Study protocol for a pragmatic randomised controlled trial of comparing enhanced acceptance and commitment therapy plus (+) added to usual aftercare versus usual aftercare only, in patients living with or beyond cancer: SUrvivors' Rehabilitation Evaluation after CANcer (SURECAN) trial.
BACKGROUND: Two million people in the UK are living with or beyond cancer and a third of them report poor quality of life (QoL) due to problems such as fatigue, fear of cancer recurrence, and concerns about returning to work. We aimed to develop and evaluate an intervention based on acceptance and commitment therapy (ACT), suited to address the concerns of cancer survivors and in improving their QoL. We also recognise the importance of exercise and vocational activity on QoL and therefore will integrate options for physical activity and return to work/vocational support, thus ACT Plus (+). METHODS: We will conduct a multi-centre, pragmatic, theory driven, randomised controlled trial. We will assess whether ACT+ including usual aftercare (intervention) is more effective and cost-effective than usual aftercare alone (control). The primary outcome is QoL of participants living with or beyond cancer measured using the Functional Assessment of Cancer Therapy: General scale (FACT-G) at 52 weeks. We will recruit 344 participants identified from secondary care sites who have completed hospital-based treatment for cancer with curative intent, with low QoL (determined by the FACT-G) and randomise with an allocation ratio of 1:1 to the intervention or control. The intervention (ACT+) will be delivered by NHS Talking Therapies, specialist services, and cancer charities. The intervention consists of up to eight sessions at weekly or fortnightly intervals using different modalities of delivery to suit individual needs, i.e. face-to-face sessions, over the phone or skype. DISCUSSION: To date, there have been no robust trials reporting both clinical and cost-effectiveness of an ACT based intervention for people with low QoL after curative cancer treatment in the UK. We will provide high quality evidence of the effectiveness and cost-effectiveness of adding ACT+ to usual aftercare provided by the NHS. If shown to be effective and cost-effective then commissioners, providers and cancer charities will know how to improve QoL in cancer survivors and their families. TRIAL REGISTRATION: ISRCTN: ISRCTN67900293 . Registered on 09 December 2019. All items from the World Health Organization Trial Registration Data Set for this protocol can be found in Additional file 2 Table S1.
The association between restricted activity and patient outcomes in older adults: systematic literature review and meta-analysis.
BACKGROUND: Restricted activity is a potential early marker of declining health in older adults. Previous studies of this association with patient outcomes have been inconclusive. This review aimed to evaluate the extent to which restricted activity is associated with decline in health. METHODS: A search was conducted for studies including people over 65 years old which investigated the association between measures of restricted activity and hospitalisation, cognitive decline, and mortality. Following data extraction by two reviewers, eligible studies were summarised using Inverse Variance Heterogeneity meta-analysis. RESULTS: The search identified 8,434 unique publications, with 11 eligible studies. Three measures of restricted activity were identified: bed rest, restricted movement, and dependency for activities of daily living (ADL). Three studies looked at hospitalisations, with two finding a significant association with bed rest or restricted movement and one showing no evidence of an association. Restricted activity was associated with a significant increase in mortality across all three measures (bed rest odds ratio [OR] 6.34, 95%CI 2.51-16.02, I2 = 76%; restricted movement OR 5.38 95%CI 2.60-11.13, I2 = 69%; general ADL dependency OR 4.65 95%CI 2.25-9.26, I2 = 84%). The significant heterogeneity observed could not be explained by restricting the analysis by length of follow-up, or measure of restricted activity. No meta-analysis was conducted on the limited evidence for cognitive decline outcomes. CONCLUSIONS: Limited studies have considered the prognostic value of restricted activity in terms of predicting future declining health. Current evidence suggests restricted activity is associated with hospitalisation and mortality, and therefore could identify a group for whom early intervention might be possible.
Mental and physical health morbidity among people in prisons: an umbrella review.
BACKGROUND: People who experience incarceration are characterised by poor health profiles. Clarification of the disease burden in the prison population can inform service and policy development. We aimed to synthesise and assess the evidence regarding the epidemiology of mental and physical health conditions among people in prisons worldwide. METHODS: In this umbrella review, five bibliographic databases (Web of Science, PubMed, PsycINFO, Embase, and Global Health) were systematically searched from inception to identify meta-analyses published up to Oct 31, 2023, which examined the prevalence or incidence of mental and physical health conditions in general prison populations. We excluded meta-analyses that examined health conditions in selected or clinical prison populations. Prevalence data were extracted from published reports and study authors were contacted for additional information. Estimates were synthesised and stratified by sex, age, and country income level. The robustness of the findings was assessed in terms of heterogeneity, excess significance bias, small-study effects, and review quality. The study protocol was pre-registered with PROSPERO, CRD42023404827. FINDINGS: Our search of the literature yielded 1909 records eligible for screening. 1736 articles were excluded and 173 full-text reports were examined for eligibility. 144 articles were then excluded due to not meeting inclusion criteria, which resulted in 29 meta-analyses eligible for inclusion. 12 of these were further excluded because they examined the same health condition. We included data from 17 meta-analyses published between 2002 and 2023. In adult men and women combined, the 6-month prevalence was 11·4% (95% CI 9·9-12·8) for major depression, 9·8% (6·8-13·2) for post-traumatic stress disorder, and 3·7% (3·2-4·1) for psychotic illness. On arrival to prison, 23·8% (95% CI 21·0-26·7) of people met diagnostic criteria for alcohol use disorder and 38·9% (31·5-46·2) for drug use disorder. Half of those with major depression or psychotic illness had a comorbid substance use disorder. Infectious diseases were also common; 17·7% (95% CI 15·0-20·7) of people were antibody-positive for hepatitis C virus, with lower estimates (ranging between 2·6% and 5·2%) found for hepatitis B virus, HIV, and tuberculosis. Meta-regression analyses indicated significant differences in prevalence by sex and country income level, albeit not consistent across health conditions. The burden of non-communicable chronic diseases was only examined in adults aged 50 years and older. Overall, the quality of the evidence was limited by high heterogeneity and small-study effects. INTERPRETATION: People in prisons have a specific pattern of morbidity that represents an opportunity for public health to address. In particular, integrating prison health within the national public health system, adequately resourcing primary care and mental health services, and improving linkage with post-release health services could affect public health and safety. Population-based longitudinal studies are needed to clarify the extent to which incarceration affects health. FUNDING: Research Foundation-Flanders, Wellcome Trust, National Institutes of Health.
Comparison of clinic and home blood pressure readings in higher risk pregnancies - Secondary analysis of the BUMP 1 trial.
OBJECTIVE: To compare clinic and home blood pressure readings in higher risk pregnancies in the antenatal period from 20 weeks gestation, and to evaluate differences between the two modalities. STUDY DESIGN: A cohort study comprising a secondary analysis of a large randomised controlled trial (BUMP 1). POPULATION: Normotensive women at higher risk of pregnancy hypertension randomised to self-monitoring of blood pressure. MAIN OUTCOME MEASURES: The primary outcome was the overall mean difference between clinic and home readings for systolic blood pressure (sBP) and diastolic blood pressure (dBP). Blood pressure readings were averaged across each gestational week for each participant and compared within the same gestational week. Calculations of the overall differences were based on the average difference for each week for each participant. RESULTS: The cohort comprised 925 participants. In total, 92 (10 %) developed a hypertensive disorder during the pregnancy. A significant difference in the overall mean sBP (clinic - home) of 1.1 mmHg (0.5-1.6 95 %CI) was noted, whereas no significant difference for the overall mean dBP was found (0.0 mmHg (-0.4-0.4 95 %CI)). No tendency of proportional bias was noted based on Bland-Altman plots. Increasing body mass index in general increased the difference (clinic - home) for both sBP and dBP in a multivariate analysis. CONCLUSIONS: No clinically significant difference was found between clinic and home blood pressure readings in normotensive higher risk pregnancies from gestational week 20+0 until 40+0. Clinic and home blood pressure readings might be considered equal during pregnancy in women who are normotensive at baseline.
Systematic review and meta-analysis: risks of anxiety disorders in offspring of parents with mood disorders
Objective: To examine the risk of anxiety disorders in offspring of parents with mood disorders. Method: We conducted a systematic review and meta-analysis. We searched 4 electronic databases (Medline, Embase, PsycINFO, and Web of Science [core collection]) to identify cross-sectional and cohort studies that examined the association between parental mood disorders (including bipolar disorder and unipolar depression) and risk of anxiety disorders in offspring. Pooled risk ratios (RRs) of overall and specific anxiety disorders were synthesized using a random effects model. Subgroup analyses and meta-regression were performed to identify moderation factors. Results: A total of 35 studies were included in the final analysis. Our results showed higher risks of all types of anxiety disorders in the offspring of parents with mood disorders (any anxiety disorder, RR = 1.82, 95% CI = 1.47-2.26), except for agoraphobia (RR = 1.08, 95% CI = 0.56-2.08), and with an especially elevated risk of panic disorder (RR = 3.07, 95% CI = 2.19-4.32). Subgroup analysis demonstrated no significant difference between the risks of anxiety disorders across the offspring of parents with bipolar disorder as opposed to unipolar depression. The absence of anxiety disorders in control parents, younger offspring age, and specific parent/offspring sex were associated with higher RRs for some anxiety disorders in offspring of parents with mood disorders. Conclusion: Our findings suggest a robust relationship between parental mood disorders and offspring anxiety disorders, and highlight the potential value of prevention and early intervention for anxiety disorders in this context. Diversity & Inclusion Statement: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list.
Using self-monitoring to detect and manage raised blood pressure and pre-eclampsia during pregnancy: the BUMP research programme and its impact.
Raised blood pressure affects around ten percent of pregnancies worldwide, causing maternal and perinatal morbidity and mortality. Self-monitoring of blood pressure during higher-risk or hypertensive pregnancy has been shown to be feasible, acceptable, safe, and no more expensive than usual care alone. Additionally, self-testing for proteinuria has been shown to be just as accurate as healthcare professional testing, creating the potential for monitoring of multiple indicators through pregnancy. The work suggests however, that an organisational shift is needed to properly use and see benefits from self-monitored readings. This paper describes the findings from a large programme of work examining the use of self-monitoring in pregnancy, summarising the findings in the context of the wider literature and current clinical context. The BUMP Research Programme developed and tested self-monitoring and self-testing interventions for pregnancy. The work showed that self-monitoring during pregnancy was feasible, acceptable, safe, and no more expensive, but did not improve the detection or control of hypertension.
Childhood Transitions Between Weight Status Categories: Evidence from the UK Millennium Cohort Study.
BACKGROUND: Assessing the cost-effectiveness of interventions targeting childhood excess weight requires estimates of the hazards of transitioning between weight status categories. Current estimates are based on studies characterized by insufficient sample sizes, a lack of national representativeness, and untested assumptions. OBJECTIVES: We sought to (1) estimate transition probabilities and hazard ratios for transitioning between childhood weight status categories, (2) test the validity of the underlying assumption in the literature that transitions between childhood bodyweight categories are time-homogeneous, (3) account for complex sampling procedures when deriving nationally representative transition estimates, and (4) explore the impact of child, maternal, and sociodemographic characteristics. METHODS: We applied a multistate transition modeling approach accounting for complex survey design to UK Millennium Cohort Study (MCS) data to predict transition probabilities and hazard ratios for weight status movements for children aged 3-17. Surveys were conducted at ages 3 (wave 2 in 2004), 5 (wave 3 in 2006), 7 (wave 4 in 2008), 11 (wave 5 in 2012), 14 (wave 6 in 2015), and 17 (wave 7 in 2018) years. We derived datasets that included repeated body mass index measurements across waves after excluding multiple births and children with missing or implausible bodyweight records. To account for the stratified cluster sample design of the MCS, we incorporated survey weights and jackknife replicates of survey weights. Using a validation dataset from the MCS, we tested the validity of our models. Finally, we estimated the relationships between state transitions and child, maternal, and sociodemographic factors. RESULTS: The datasets for our primary analysis consisted of 10,399 children for waves 2-3, 10,729 for waves 3-4, 9685 for waves 4-5, 8593 for waves 5-6, and 7085 for waves 6-7. All datasets consisted of roughly equal splits of boys and girls. Under the assumption of time-heterogeneous transition rates (our base-case model), younger children (ages 3-5 and 5-7 years) had significantly higher annual transition probabilities of moving from healthy weight to overweight (0.033, 95% confidence interval [CI] 0.026-0.041, and 0.027, 95% CI 0.021-0.033, respectively) compared to older children (0.015, 95% CI 0.012-0.018, at ages 7-11; 0.018, 95% CI 0.013-0.023, at ages 11-14; and 0.018, 95% CI 0.013-0.025 at ages 14-17 years). However, the resolution of unhealthy weight was more strongly age-dependent than transitions from healthy weight to non-healthy weight states. Transition hazards differed by child, maternal, and sociodemographic factors. CONCLUSIONS: Our models generated estimates of bodyweight status transitions in a representative UK childhood population. Compared to our scenario models (i.e., time-homogeneous transition rates), our base-case model fits the observed data best, indicating a non-time-homogeneous pattern in transitions between bodyweight categories during childhood. Transition hazards varied significantly by age and across subpopulations, suggesting that conducting subgroup-specific cost-effectiveness analyses of childhood weight management interventions will optimize decision-making.
European Society of Cardiology Quality indicators for the care and outcomes of adults undergoing transcatheter aortic valve implantation.
BACKGROUND AND AIMS: To develop a suite of quality indicators (QIs) for the evaluation of the care and outcomes for adults undergoing transcatheter aortic valve intervention (TAVI). METHODS: We followed the European Society of Cardiology (ESC) methodology for the development of QIs. Key domains were identified by constructing a conceptual framework for the delivery of TAVI care. A list of candidate QIs were developed by conducting a systematic review of the literature. A modified Delphi method was then used to select the final set of QIs. Finally, we mapped the QIs to the EuroHeart Data Standards for TAVI to ascertain the extent to which the EuroHeart TAVI registry captures information to calculate the QIs. RESULTS: We formed an international group of experts in quality improvement and TAVI, including representatives from the European Association of Percutaneous Cardiovascular Interventions, the European Association of Cardiovascular Imaging and the Association of Cardiovascular Nursing & Allied Professions. In total, 27 QIs were selected across eight domains of TAVI care, comprising 22 main (81%) and five secondary (19%) QIs. Of these, 19/27 (70%) are now being utilised in the EuroHeart TAVI registry. CONCLUSION: We present the 2023 ESC QIs for TAVI, developed using a standard methodology and in collaboration with ESC Associations. The EuroHeart TAVI registry allows calculation of the majority of the QIs, which may be used for benchmarking care and quality improvement initiatives.
The diagnostic accuracy of cardiac ultrasound for acute myocardial ischemia in the emergency department: a systematic review and meta-analysis.
BACKGROUND: Chest pain is responsible for millions of visits to the emergency department (ED) annually. Cardiac ultrasound can detect ischemic changes, but varying accuracy estimates have been reported in previous studies. We synthetized the available evidence to yield more precise estimates of the accuracy of cardiac ultrasound for acute myocardial ischemia in patients with chest pain in the ED and to assess the effect of different clinical characteristics on test accuracy. METHODS: A systematic search for studies assessing the diagnostic accuracy of cardiac ultrasound for myocardial ischemia in the ED was conducted in MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Web of Science, two trial registries and supplementary methods, from inception to December 6th, 2022. Prospective cohort, cross-sectional, case-control studies and randomized controlled trials (RCTs) that included data on diagnostic accuracy were included. Risk of bias was assessed with the QUADAS-2 tool and a bivariate hierarchical model was used for meta-analysis with paired Forest and SROC plots used to present the results. Subgroup analyses was conducted on clinically relevant factors. RESULTS: Twenty-nine studies were included, with 5043 patients. The overall summary sensitivity was 79.3% (95%CI 69.0-86.8%) and specificity was 87.3% (95%CI 79.9-92.2%), with substantial heterogeneity. Subgroup analyses showed increased sensitivity in studies where ultrasound was conducted at ED admission and increased specificity in studies that excluded patients with previous heart disease, when the target condition was acute coronary syndrome, or when final chart review was used as the reference standard. There was very low certainty in the results based on serious risk of bias and indirectness in most studies. CONCLUSIONS: Cardiac ultrasound may have a potential role in the diagnostic pathway of myocardial ischemia in the ED; however, a pooled accuracy must be interpreted cautiously given substantial heterogeneity and that important patient and test characteristics affect its diagnostic performance. PROTOCOL REGISTRATION: PROSPERO (CRD42023392058).
Effects of preoperative and postoperative resistance exercise interventions on recovery of physical function in patients undergoing abdominal surgery for cancer: a systematic review of randomised controlled trials.
OBJECTIVE: To systematically review the effects of preoperative and postoperative resistance exercise training on the recovery of physical function in patients undergoing abdominal surgery for cancer. DATA SOURCES: A systematic review of English articles using Medline, Physiotherapy Evidence Database, CINAHL and the Cochrane Library electronic databases was undertaken. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies were included if they used a randomised, quasi-randomised or controlled trial study design and compared the effects of a muscle-strengthening exercise intervention (±other therapy) with a comparative non-exercise group; involved adult participants (≥18 years) who had elected to undergo abdominal surgery for cancer; and used muscle strength, physical function, self-reported functional ability, range of motion and/or a performance-based test as an outcome measure. RESULTS: Following screening of titles and abstracts of the 588 publications retrieved from the initial search, 24 studies met the inclusion criteria and were accessed for review of the full-text version of the article, and 2 eligible studies met the inclusion criteria and were included in the review. One exercise programme was undertaken preoperatively and the other postoperatively, until discharge from hospital. The exercise interventions of the included studies were performed for five and eight sessions, respectively. There were no differences between groups in either study. CONCLUSION: The only two studies designed to determine whether preoperative or postoperative resistance muscle-strengthening exercise programmes improved or negatively affected physical function outcomes in patients undergoing abdominal surgery for cancer provide inconclusive results.