Cardiovascular disease risk communication and prevention: a meta-analysis.

BACKGROUND AND AIMS: Knowledge of quantifiable cardiovascular disease (CVD) risk may improve health outcomes and trigger behavioural change in patients or clinicians. This review aimed to investigate the impact of CVD risk communication on patient-perceived CVD risk and changes in CVD risk factors. METHODS: PubMed, Embase, and PsycINFO databases were searched from inception to 6 June 2023, supplemented by citation analysis. Randomized trials that compared any CVD risk communication strategy versus usual care were included. Paired reviewers independently screened the identified records and extracted the data; disagreements were resolved by a third author. The primary outcome was the accuracy of risk perception. Secondary outcomes were clinician-reported changes in CVD risk, psychological responses, intention to modify lifestyle, and self-reported changes in risk factors and clinician prescribing of preventive medicines. RESULTS: Sixty-two trials were included. Accuracy of risk perception was higher among intervention participants (odds ratio = 2.31, 95% confidence interval = 1.63 to 3.27). A statistically significant improvement in overall CVD risk scores was found at 6-12 months (mean difference = -0.27, 95% confidence interval = -0.45 to -0.09). For primary prevention, risk communication significantly increased self-reported dietary modification (odds ratio = 1.50, 95% confidence interval = 1.21 to 1.86) with no increase in intention or actual changes in smoking cessation or physical activity. A significant impact on patients' intention to start preventive medication was found for primary and secondary prevention, with changes at follow-up for the primary prevention group. CONCLUSIONS: In this systematic review and meta-analysis, communicating CVD risk information, regardless of the method, reduced the overall risk factors and enhanced patients' self-perceived risk. Communication of CVD risk to patients should be considered in routine consultations.

Partial synthetic models of FeMoco with sulfide and carbyne ligands: Effect of interstitial atom in nitrogenase active site.

Nitrogen-fixing organisms perform dinitrogen reduction to ammonia at an Fe-M (M = Mo, Fe, or V) cofactor (FeMco) of nitrogenase. FeMco displays eight metal centers bridged by sulfides and a carbide having the MFe7S8C cluster composition. The role of the carbide ligand, a unique motif in protein active sites, remains poorly understood. Toward addressing how the carbon bridge affects the physical and chemical properties of the cluster, we isolated synthetic models of subsite MFe3S3C displaying sulfides and a chelating carbyne ligand. We developed synthetic protocols for structurally related clusters, [Tp*M'Fe3S3X]n-, where M' = Mo or W, the bridging ligand X = CR, N, NR, S, and Tp* = Tris(3,5-dimethyl-1-pyrazolyl)hydroborate, to study the effects of the identity of the heterometal and the bridging X group on structure and electrochemistry. While the nature of M' results in minor changes, the chelating, µ3-bridging carbyne has a large impact on reduction potentials, being up to 1 V more reducing compared to nonchelating N and S analogs.

Synthesis of a Fe3-Carbyne Motif by Oxidation of an Alkyl Ligated Iron-Sulfur (WFe3S3) Cluster.

The presence of a carbide ligand in the active site of nitrogenases remains an unusual example of organometallic chemistry employed by a protein. Carbide incorporation into the MFe7S9C cluster involves complex biosynthesis, but analogous synthetic methodologies are limited. Herein, we present a new synthetic strategy for incorporating carbon based bridging ligands into iron-sulfur clusters. Starting from a halide precursor, a WFe3S3 cluster displaying three terminal alkyl ligands and an open Fe3 face was prepared. Oxidation results in loss of alkane and formation of a µ3-carbyne. Characterization of these clusters and mechanistic studies are presented.

CLN2 disease resulting from a novel homozygous deep intronic splice variant in TPP1 discovered using long-read sequencing.

Neuronal ceroid lipofuscinosis type 2 (CLN2) is an autosomal recessive neurodegenerative disorder with enzyme replacement therapy available. We present two siblings with a clinical diagnosis of CLN2 disease, but no identifiable TPP1 variants after standard clinical testing. Long-read sequencing identified a homozygous deep intronic variant predicted to affect splicing, confirmed by clinical DNA and RNA sequencing. This case demonstrates how traditional laboratory assays can complement emerging molecular technologies to provide a precise molecular diagnosis.

Overuse of medications in low- and middle-income countries: a scoping review.

Objective: To identify and summarize the evidence about the extent of overuse of medications in low- and middle-income countries, its drivers, consequences and potential solutions. Methods: We conducted a scoping review by searching the databases PubMed®, Embase®, APA PsycINFO® and Global Index Medicus using a combination of MeSH terms and free text words around overuse of medications and overtreatment. We included studies in any language published before 25 October 2021 that reported on the extent of overuse, its drivers, consequences and solutions. Findings: We screened 3489 unique records and included 367 studies reporting on over 5.1 million prescriptions across 80 low- and middle-income countries - with studies from 58.6% (17/29) of all low-, 62.0% (31/50) of all lower-middle- and 60.0% (33/55) of all upper-middle-income countries. Of the included studies, 307 (83.7%) reported on the extent of overuse of medications, with estimates ranging from 7.3% to 98.2% (interquartile range: 30.2-64.5). Commonly overused classes included antimicrobials, psychotropic drugs, proton pump inhibitors and antihypertensive drugs. Drivers included limited knowledge of harms of overuse, polypharmacy, poor regulation and financial influences. Consequences were patient harm and cost. Only 11.4% (42/367) of studies evaluated solutions, which included regulatory reforms, educational, deprescribing and audit-feedback initiatives. Conclusion: Growing evidence suggests overuse of medications is widespread within low- and middle-income countries, across multiple drug classes, with few data of solutions from randomized trials. Opportunities exist to build collaborations to rigorously develop and evaluate potential solutions to reduce overuse of medications.

Misdiagnosis of Uncomplicated Cellulitis: a Systematic Review and Meta-analysis.

BACKGROUND: Cellulitis is a clinical diagnosis with several mimics and no gold standard diagnostic criteria. Misdiagnosis is common. This review aims to quantify the proportion of cellulitis misdiagnosis in primary or unscheduled care settings based on a second clinical assessment and describe the proportion and types of alternative diagnoses. METHODS: Electronic searches of Medline, Embase and Cochrane library (including CENTRAL) using MeSH and other subject terms identified 887 randomised and non-randomised clinical trials, and cohort studies. Included articles assessed the proportion of cellulitis misdiagnosis in primary or unscheduled care settings through a second clinical assessment up to 14 days post initial diagnosis of uncomplicated cellulitis. Studies on infants and patients with (peri-)orbital, purulent and severe or complex cellulitis were excluded. Screening and data extraction was conducted independently in pairs. Risk of bias was assessed using a modified risk of bias tool from Hoy et al. Meta-analyses were undertaken where ≥ 3 studies reported the same outcome. RESULTS: Nine studies conducted in the USA, UK and Canada, including a total of 1600 participants, were eligible for inclusion. Six studies were conducted in the inpatient setting; three were in outpatient clinics. All nine included studies provided estimates of the proportion cellulitis misdiagnosis, with a range from 19 to 83%. The mean proportion misdiagnosed was 41% (95% CI 28 to 56% for random effects model). Heterogeneity between studies was very high both statistically (I2 96%, p-value for heterogeneity < 0.001) and clinically. Of the misdiagnoses, 54% were attributed to three conditions (stasis dermatitis, eczematous dermatitis and edema/lymphedema). DISCUSSION: The proportion of cellulitis misdiagnosis when reviewed within 14 days was substantial though highly variable, with the majority attributable to three diagnoses. This highlights the need for timely clinical reassessment and system initiatives to improve diagnostic accuracy of cellulitis and its most common mimics. TRIAL REGISTRATION: Open Science Framework ( https://osf.io/9zt72 ).

Gender Differences in Perceived Working Conditions of General Practitioners During the COVID-19 Pandemic-a Cross-Sectional Study.

BACKGROUND: The ongoing COVID-19 pandemic has revealed gender-specific differences between general practitioners in adapting to the posed challenges. As primary care workforce is becoming increasingly female, in many countries, it is essential to take a closer look at gender-specific influences when the global health care system is confronted with a crisis. OBJECTIVE: To explore gender-specific differences in the perceived working conditions and gender-specific differences in challenges facing GPs at the beginning of the COVID-19 pandemic in 2020. DESIGN: Online survey in seven countries. PARTICIPANTS: 2,602 GPs from seven countries (Austria, Australia, Switzerland, Germany, Hungary, Italy, Slovenia). Of the respondents, 44.4% (n = 1,155) were women. MAIN MEASURES: Online survey. We focused on gender-specific differences in general practitioners' perceptions of working conditions at the beginning of the COVID-19 pandemic in 2020. KEY RESULTS: Female GPs rated their skills and self-confidence significantly lower than male GPs (f: 7.1, 95%CI: 6.9-7.3 vs. m: 7.6, 95%CI 7.4-7.8; p < .001), and their perceived risk (concerned about becoming infected or infecting others) higher than men (f: 5.7, 95%CI: 5.4-6.0 vs. m: 5.1, 95%CI: 4.8-5.5; p = .011). Among female GPs, low self-confidence in the treatment of COVID-19 patients appear to be common. Results were similar in all of the participating countries. CONCLUSIONS: Female and male GPs differed in terms of their self-confidence when dealing with COVID-19-related issues and their perceptions of the risks arising from the pandemic. To ensure optimal medical care, it is important that GPs realistically assess their own abilities and overall risk.

Volunteering on Heritage at Risk sites and wellbeing: A qualitative interview study.

INTRODUCTION: We explored experiences of volunteering in Heritage at Risk (HAR) projects, intended to mitigate the deterioration to historic assets, and the relationship with wellbeing. We aimed to understand the value of HAR to volunteers' wellbeing and relationships between HAR programme characteristics such as location, asset type and type of activity. METHODS: We used a qualitative design with semi-structured interviews of a purposive sample of volunteers recruited via Historic England (HE), employing Systematic Grounded Theory involving open, axial and selective coding. FINDINGS: We interviewed 35 volunteers (18 male and 17 female) participating in 10 HAR projects. We identified six themes from the data analysis. (1) Purpose-was associated with volunteering motivations; there were some barriers to volunteering and many types of facilitators, including accessibility to local heritage sites. (2) Being-volunteers showed an appreciation and attachment to their place of residence. (3) Capacity-to learn heritage-specific skills and diversify experiences in learning new skills (life, technical and personal). (4) Sharing-community engagement, connectedness, and inclusivity captured diversity and inclusion within volunteers across age, ethnicity, ability, and gender. (5) Self-nurture-HAR volunteering created physical, psychological, and social benefits with limited risks and adverse outcomes. (6) Self-actualisation-described volunteers reflecting on their experiences. CONCLUSION: HAR volunteering was associated with positive physical, social and psychological wellbeing outcomes. The study provides an evidence base for specific wellbeing benefits of volunteering at Heritage at Risk sites, although we could not conclude that HAR project activity was the cause of increased wellbeing. PUBLIC CONTRIBUTION: Staff from HE were involved in designing the project brief. In selecting the HAR project sites, we took advice and recommendations from HE staff across all their six regional offices.

Co-designing nutrition interventions with consumers: A scoping review.

BACKGROUND: There is little known about nutrition intervention research involving consumer co-design. The aim of this scoping review was to identify and synthesise the existing evidence on the current use and extent of consumer co-design in nutrition interventions. METHODS: This scoping review is in line with the methodological framework developed by Arksey and O'Malley and refined by the Joanna Briggs Institute using an adapted 2weekSR approach. We searched Medline, EMBASE, PsycInfo, CINAHL and Cochrane. Only studies that included consumers in the co-design and met the 'Collaborate' or 'Empower' levels of the International Association of Public Participation's Public Participation Spectrum were included. Studies were synthesised according to two main concepts: (1) co-design for (2) nutrition interventions. RESULTS: The initial search yielded 8157 articles, of which 19 studies were included (comprising 29 articles). The studies represented a range of intervention types and participants from seven countries. Sixteen studies were published in the past 5 years. Co-design was most often used for intervention development, and only two studies reported a partnership with consumers across all stages of research. Overall, consumer involvement was not well documented. No preferred co-design framework or approach was reported across the various studies. CONCLUSIONS: Consumer co-design for nutrition interventions has become more frequent in recent years, but genuine partnerships with consumers across all stages of nutrition intervention research remain uncommon. There is an opportunity to improve the reporting of consumer involvement in co-design and enable equal partnerships with consumers in nutrition research.

Comparison of Telephone and Video Telehealth Consultations: Systematic Review.

BACKGROUND: Telehealth has been used for health care delivery for decades, but the COVID-19 pandemic greatly accelerated the uptake of telehealth in many care settings globally. However, few studies have carried out a direct comparison among different telehealth modalities, with very few studies having compared the effectiveness of telephone and video telehealth modalities. OBJECTIVE: This study aimed to identify and synthesize randomized controlled trials (RCTs) comparing synchronous telehealth consultations delivered by telephone and those conducted by video with outcomes such as clinical effectiveness, patient safety, cost-effectiveness, and patient and clinician satisfaction with care. METHODS: PubMed (MEDLINE), Embase, and CENTRAL were searched via the Cochrane Library from inception until February 10, 2023, for RCTs without any language restriction. Forward and backward citation searches were conducted on included RCTs. The Cochrane Risk of Bias 2 tool was used to assess the quality of the studies. We included studies carried out in any health setting-involving all types of outpatient cohorts and all types of health care providers-that compared synchronous video consultations directly with telephone consultations and reported outcomes specified in the objective. We excluded studies of clinician-to-clinician telehealth consults, hospitalized patients, and asynchronous consultations. RESULTS: Sixteen RCTs-10 in the United States, 3 in the United Kingdom, 2 in Canada, and 1 in Australia involving 1719 participants-were included in the qualitative and quantitative analyses. Most of the telehealth interventions were for hospital-based outpatient follow-ups, monitoring, and rehabilitation (n=13). The 3 studies that were conducted in the community all focused on smoking cessation. In half of the studies, nurses delivered the care (n=8). Almost all included studies had high or unclear risk of bias, mainly due to bias in the randomization process and selection of reported results. The trials found no substantial differences between telephone and video telehealth consultations with regard to clinical effectiveness, patient satisfaction, and health care use (cost-effectiveness) outcomes. None of the studies reported on patient safety or adverse events. We did not find any study on telehealth interventions for diagnosis, initiating new treatment, or those conducted in a primary care setting. CONCLUSIONS: Based on a small set of diverse trials, we found no notable differences between telephone and video consultations for the management of patients with an established diagnosis. There is also a significant lack of telehealth research in primary care settings despite its high uptake.

High-Spin and Reactive Fe13 Cluster with Exposed Metal Sites.

Atomically defined large metal clusters have applications in new reaction development and preparation of materials with tailored properties. Expanding the synthetic toolbox for reactive high nuclearity metal complexes, we report a new class of Fe clusters, Tp*4 W4 Fe13 S12 , displaying a Fe13 core with M-M bonds that has precedent only in main group and late metal chemistry. M13 clusters with closed shell electron configurations can show significant stability and have been classified as superatoms. In contrast, Tp*4 W4 Fe13 S12 displays a large spin ground state of S=13. This compound performs small molecule activations involving the transfer of up to 12 electrons resulting in significant cluster rearrangements.

A rapid and non-invasive proteomic analysis using DBS and buccal swab for multiplexed second-tier screening of Pompe disease and Mucopolysaccharidosis type I.

PURPOSE: Current newborn screening programs for Pompe disease (PD) and mucopolysaccharidosis type I (MPS I) suffer from a high false positive rate and long turnaround time for clinical follow up. This study aimed to develop a novel proteomics-based assay for rapid and accurate second-tier screening of PD and MPS I. A fast turnaround assay would enable the identification of severe cases who need immediate clinical follow up and treatment. METHODS: We developed an immunocapture coupled with mass spectrometry-based proteomics (Immuno-SRM) assay to quantify GAA and IDUA proteins in dried blood spots (DBS) and buccal swabs. Sensitivity, linearity, reproducibility, and protein concentration range in healthy control samples were determined. Clinical performance was evaluated in known PD and MPS I patients as well as pseudodeficiency and carrier cases. RESULTS: Using three 3.2 mm punches (~13.1 µL of blood) of DBS, the assay showed reproducible and sensitive quantification of GAA and IDUA. Both proteins can also be quantified in buccal swabs with high reproducibility and sensitivity. Infantile onset Pompe disease (IOPD) and severe MPS I cases are readily identifiable due to the absence of GAA and IDUA, respectively. In addition, late onset Pompe disease (LOPD) and attenuated MPS I patients showed much reduced levels of the target protein. By contrast, pseudodeficiency and carrier cases exhibited significant higher target protein levels compared to true patients. CONCLUSION: Direct quantification of endogenous GAA and IDUA peptides in DBS by Immuno-SRM can be used for second-tier screening to rapidly identify severe PD and MPS I patients with a turnaround time of <1 week. Such patients could benefit from immediate clinical follow up and possibly earlier treatment.

Telehealth v. face-to-face provision of care to patients with depression: a systematic review and meta-analysis.

Ensuring continuity of care for patients with major depressive disorders poses multiple challenges. We conducted a systematic review and meta-analysis of randomised controlled trials comparing real-time telehealth to face-to-face therapy for individuals with depression. We searched Medline, Embase, and Cochrane Central (to November 2020), conducted a citation analysis (January 2021), and searched clinical trial registries (March 2021). We included randomised controlled trials comparing similar or identical care, delivered via real-time telehealth (phone, video) to face-to-face. Outcomes included: depression severity, quality of life, therapeutic alliance, and care satisfaction. Where data were sufficient, mean differences were calculated. Nine trials (1268 patients) were included. There were no differences between telehealth and face-to-face care for depression severity at post-treatment (SMD -0.04, 95% CI -0.21 to 0.13, p = 0.67) or at other time points, except at 9 months post-treatment (SMD -0.39, 95% CI -0.75 to -0.02, p = 0.04). One trial reported no differences in quality-of-life scores at 3- or 12-months post-treatment. One trial found no differences in therapeutic alliance at weeks 4 and 14 of treatment. There were no differences in treatment satisfaction between telehealth and face-to-face immediately post-treatment (SMD -0.14, 95% CI -0.56 to 0.28, p = 0.51) or at 3 or 12-months. Evidence suggests that for patients with depression or depression symptoms, the provision of care via telehealth may be a viable alternative to the provision of care face-to-face. However, additional trials are needed with longer follow-up, conducted in a wider range of settings, and with younger patients.

The impact of antibiotics on clinical response over time in uncomplicated cellulitis: a systematic review and meta-analysis.

PURPOSE: Antibiotic treatment of uncomplicated cellulitis is highly variable with respect to agent, dose, and route of administration. As there is uncertainty about optimal/appropriate time to reassess, we aimed to assess time to clinical response. METHODS: We conducted a systematic review of randomized controlled trials reporting clinical response of uncomplicated cellulitis to antibiotic treatment over multiple timepoints. PubMed, Embase, CENTRAL, WHO ICTRP, and clinicaltrials.gov were searched from inception to June 2021 without language restrictions. The primary outcome was time to clinical response. Other outcomes were components of clinical response (pain, severity score, redness, edema measured at ≥ 2 timepoints) and the proportion of patients with treatment failure. We performed a pooled estimate of the average time to clinical response together with 95% confidence intervals using a random effects model. RESULTS: We included 32 randomized controlled trials (n = 13,576 participants). The mean time to clinical response was 1.68 days (95%CI 1.48-1.88; I2 = 76%). The response to treatment for specific components was as follows: ~ 50% reduction of pain and severity score by day 5, a ~ 33% reduction in area of redness by day 2-3, and a 30-50% reduction of proportion of patients with edema by day 2-4. Treatment failure was variably defined with an overall failure rate of 12% (95%CI 9-16%). CONCLUSION: The best available data suggest the optimal time to clinical reassessment is between 2 and 4 days, but this must be interpreted with caution due to considerable heterogeneity and small number of included studies.

The effectiveness of parasympathomimetics for treating underactive bladder: A systematic review and meta-analysis.

AIMS: Biological rationale suggests that parasympathomimetics (cholinergic receptor stimulating agents) could be beneficial for patients with underactive bladder. However, no systematic review with meta-analysis addressing potential benefits or adverse effects exists. The aim of this review was to assess the effectiveness, both benefits and harms, of using parasympathomimetics for the treatment of underactive bladder. METHODS: The protocol was registered in PROSPERO, and searches undertaken in PubMed, Embase, and CENTRAL, including randomized and non-randomized controlled trials of patients with underactive bladder, comparing parasympathomimetic to placebo, no treatment, or other pharmaceuticals. Risk ratios, odds ratios, and mean differences were calculated. RESULTS: Twelve trials with 3024 participants were included. There was a significant difference between parasympathomimetics and comparators (favoring parasympathomimetics) in the number of patients with urinary retention (risk ratio 0.55, 95% confidence interval [CI] 0.3-0.98, p = 0.04, low quality of evidence). There was no difference in mean postvoid volume overall (MD -41.4 ml, 95% CI -92.0 to 9.1, p = 0.11, low quality of evidence). There was a significant difference at up to 1 week post-intervention, favoring parasympathomimetics (MD -77.5 ml, 95% CI -90.9 to -64.1, p < 0.001, low quality of evidence), but no difference at 1 month post-intervention. There was no difference in adverse events (odds ratio 1.19, 95% CI 0.62-2.28, p = 0.6, moderate quality of evidence). CONCLUSIONS: The evidence supporting the use of parasympathomimetics is of low quality, with relatively short follow-up durations. Overall, it is not possible to draw clear evidence-based conclusions from the current literature, presenting the use of parasympathomimetics for treating underactive bladder as a key area that requires future well-controlled clinical trials.

Occupational therapy for cognitive impairment in stroke patients.

BACKGROUND: Cognitive impairment is a frequent consequence of stroke and can impact on a person's ability to perform everyday activities. Occupational therapists use a range of interventions when working with people who have cognitive impairment poststroke. This is an update of a Cochrane Review published in 2010. OBJECTIVES: To assess the impact of occupational therapy on activities of daily living (ADL), both basic and instrumental, global cognitive function, and specific cognitive abilities in people who have cognitive impairment following a stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, Embase, four other databases (all last searched September 2020), trial registries, and reference lists. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials that evaluated an intervention for adults with clinically defined stroke and confirmed cognitive impairment. The intervention needed either to be provided by an occupational therapist or considered within the scope of occupational therapy practice as defined in the review. We excluded studies focusing on apraxia or perceptual impairments or virtual reality interventions as these are covered by other Cochrane Reviews. The primary outcome was basic activities of daily living (BADL) such as dressing, feeding, and bathing. Secondary outcomes were instrumental ADL (IADL) (e.g. shopping and meal preparation), community integration and participation, global cognitive function and specific cognitive abilities (including attention, memory, executive function, or a combination of these), and subdomains of these abilities. We included both observed and self-reported outcome measures. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies that met the inclusion criteria, extracted data, and assessed the certainty of the evidence. A third review author moderated disagreements if consensus was not reached. We contacted trial authors for additional information and data, where available. We assessed the certainty of key outcomes using GRADE.  MAIN RESULTS: We included 24 trials from 11 countries involving 1142 (analysed) participants (two weeks to eight years since stroke onset). This update includes 23 new trials in addition to the one study included in the previous version. Most were parallel randomised controlled trials except for one cross-over trial and one with a two-by-two factorial design. Most studies had sample sizes under 50 participants. Twenty studies involved a remediation approach to cognitive rehabilitation, particularly using computer-based interventions. The other four involved a compensatory and adaptive approach. The length of interventions ranged from 10 days to 18 weeks, with a mean total length of 19 hours. Control groups mostly received usual rehabilitation or occupational therapy care, with a few receiving an attention control that was comparable to usual care; two had no intervention (i.e. a waiting list). Apart from high risk of performance bias for all but one of the studies, the risk of bias for other aspects was mostly low or unclear.  For the primary outcome of BADL, meta-analysis found a small effect on completion of the intervention with a mean difference (MD) of 2.26 on the Functional Independence Measure (FIM) (95% confidence interval (CI) 0.17 to 4.22; P = 0.03, I2 = 0%; 6 studies, 336 participants; low-certainty evidence). Therefore, on average, BADL improved by 2.26 points on the FIM that ranges from 18 (total assist) to 126 (complete independence). On follow-up, there was insufficient evidence of an effect at three months (MD 10.00, 95% CI -0.54 to 20.55; P = 0.06, I2 = 53%; 2 studies, 73 participants; low-certainty evidence), but evidence of an effect at six months (MD 11.38, 95% CI 1.62 to 21.14, I2 = 12%; 2 studies, 73 participants; low-certainty evidence). These differences are below 22 points which is the established minimal clinically important difference (MCID) for the FIM for people with stroke. For IADL, the evidence is very uncertain about an effect (standardised mean difference (SMD) 0.94, 95% CI 0.41 to 1.47; P = 0.0005, I2 = 98%; 2 studies, 88 participants). For community integration, we found insufficient evidence of an effect (SMD 0.09, 95% CI -0.35 to 0.54; P = 0.68, I2 = 0%; 2 studies, 78 participants). There was an improvement of clinical importance in global cognitive functional performance after the intervention (SMD 0.35, 95% CI 0.16 to 0.54; P = 0.0004, I2 = 0%; 9 studies, 432 participants; low-certainty evidence), equating to 1.63 points on the Montreal Cognitive Assessment (MoCA) (95% CI 0.75 to 2.52), which exceeds the anchor-based MCID of the MoCA for stroke rehabilitation patients of 1.22. We found some effect for attention overall (SMD -0.31, 95% CI -0.47 to -0.15; P = 0.0002, I2 = 20%; 13 studies, 620 participants; low-certainty evidence), equating to a difference of 17.31 seconds (95% CI 8.38 to 26.24), and for executive functional performance overall (SMD 0.49, 95% CI 0.31 to 0.66; P < 0.00001, I2 = 74%; 11 studies, 550 participants; very low-certainty evidence), equating to 1.41 points on the Frontal Assessment Battery (range: 0-18). Of the cognitive subdomains, we found evidence of effect of possible clinical importance, immediately after intervention, for sustained visual attention (moderate certainty) equating to 15.63 seconds, for working memory (low certainty) equating to 59.9 seconds, and thinking flexibly (low certainty), compared to control. AUTHORS' CONCLUSIONS: The effectiveness of occupational therapy for cognitive impairment poststroke remains unclear. Occupational therapy may result in little to no clinical difference in BADL immediately after intervention and at three and six months' follow-up. Occupational therapy may slightly improve global cognitive performance of a clinically important difference immediately after intervention, likely improves sustained visual attention slightly, and may slightly increase working memory and flexible thinking after intervention. There is evidence of low or very low certainty or insufficient evidence for effect on other cognitive domains, IADL, and community integration and participation.  Given the low certainty of much of the evidence in our review, more research is needed to support or refute the effectiveness of occupational therapy for cognitive impairment after stroke. Future trials need improved methodology to address issues including risk of bias and to better report the outcome measures and interventions used.

Quantitative analysis of the natural history of prolidase deficiency: description of 17 families and systematic review of published cases.

PURPOSE: Prolidase deficiency is a rare inborn error of metabolism causing ulcers and other skin disorders, splenomegaly, developmental delay, and recurrent infections. Most of the literature is constituted of isolated case reports. We aim to provide a quantitative description of the natural history of the condition by describing 19 affected individuals and reviewing the literature. METHODS: Nineteen patients were phenotyped per local institutional procedures. A systematic review following PRISMA criteria identified 132 articles describing 161 patients. Main outcome analyses were performed for manifestation frequency, diagnostic delay, overall survival, symptom-free survival, and ulcer-free survival. RESULTS: Our cohort presented a wide variability of severity. Autoimmune disorders were found in 6/19, including Crohn disease, systemic lupus erythematosus, and arthritis. Another immune finding was hemophagocytic lymphohistiocytosis (HLH). Half of published patients were symptomatic by age 4 and had a delayed diagnosis (mean delay 11.6 years). Ulcers were present initially in only 30% of cases, with a median age of onset at 12 years old. CONCLUSION: Prolidase deficiency has a broad range of manifestations. Symptoms at onset may be nonspecific, likely contributing to the diagnostic delay. Testing for this disorder should be considered in any child with unexplained autoimmunity, lower extremity ulcers, splenomegaly, or HLH.

A journey towards answers: Bonnie Odgers Meets Dr. John Graham.

The importance of understanding HIST1H1E Syndrome is sharing our family's personal journey to find a diagnosis for our daughter, Bonnie Odgers. This syndrome has also been referred to as Rahman Syndrome and HIST1H1E Neurodevelopmental Syndrome depending upon the origin of research. Characteristics of HIST1H1E are curved fingers, full cheeks, high forehead, speech impairments and mild to severe intellectual disability. This article reveals the Odgers' family journey towards a diagnosis, the key physicians research through whole exome genetic testing and revealing characteristics of HIST1H1E.

'The ethics approval took 20 months on a trial which was meant to help terminally ill cancer patients. In the end we had to send the funding back': a survey of views on human research ethics reviews.

BACKGROUND: We conducted a survey to identify what types of health/medical research could be exempt from research ethics reviews in Australia. METHODS: We surveyed Australian health/medical researchers and Human Research Ethics Committee (HREC) members. The survey asked whether respondents had previously changed or abandoned a project anticipating difficulties obtaining ethics approval, and presented eight research scenarios, asking whether these scenarios should or should not be exempt from ethics review, and to provide (optional) comments. Qualitative data were analysed thematically; quantitative data in R. RESULTS: We received 514 responses. Forty-three per cent of respondents to whom the question applied, reported changing projects in anticipation of obstacles from the ethics review process; 25% reported abandoning projects for this reason. Research scenarios asking professional staff to provide views in their area of expertise were most commonly exempted from ethics review (to prioritise systematic review topics 84%, on software strengths/weaknesses 85%); scenarios involving surplus samples (82%) and N-of-1 (single case) studies (76%) were most commonly required to undergo ethics review. HREC members were 26% more likely than researchers to require ethics review. Need for independent oversight, and low risk, were most frequently cited in support of decisions to require or exempt from ethics review, respectively. CONCLUSIONS: Considerable differences exist between researchers and HREC members, about when to exempt from review the research that ultimately serves the interests of patients and the public. It is widely accepted that evaluative research should be used to reduce clinical uncertainties-the same principle should apply to ethics reviews.

A Community Jury on initiating weight management conversations in primary care.

BACKGROUND: Current guidelines recommend that patients attending general practice should be screened for excess weight, and provided with weight management advice. OBJECTIVE: This study sought to elicit the views of people with overweight and obesity about the role of GPs in initiating conversations about weight management. METHODS: Participants with a body mass index ≥25 were recruited from a region in Australia to take part in a Community Jury. Over 2 days, participants (n = 11) deliberated on two interconnected questions: 'Should GPs initiate discussions about weight management?' And 'if so, when: (a) opportunistically, (b) in the context of disease prevention, (c) in the context of disease management or (d) other?' The jury deliberations were analysed qualitatively to elicit their views and recommendations. RESULTS: The jury concluded GPs should be discussing weight management, but within the broader context of general health. The jury were divided about the utility of screening. Jurors felt GPs should initiate the conversation if directly relevant for disease prevention or management, otherwise GPs should provide opportunities for patients to consent to the issue being raised. CONCLUSION: The jury's verdict suggests informed people affected by overweight and obesity believe GPs should discuss weight management with their patients. GPs should feel reassured that discussions are likely to be welcomed by patients, particularly if embedded within a more holistic focus on person-centred care. PUBLIC CONTRIBUTION: Members of the public took part in the conduct of this study as jurors, but were not involved in the design, analysis or write-up.