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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long COVID. We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02–8.39), hair loss (3.99, 3.63–4.39), sneezing (2.77, 1.40–5.50), ejaculation difficulty (2.63, 1.61–4.28) and reduced libido (2.36, 1.61–3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors. A retrospective analysis of primary care records in the United Kingdom reveals individual symptoms associated with SARS-CoV-2 infections, which persisted for 12 weeks or more after infection, as well as risk factors associated with developing long COVID.

BackgroundPersons experiencing homelessness (PEH) often use hospital Emergency Department (ED) as the only source of healthcare. The aim of this study was to undertake a systematic review to identify the prevalence, clinical reasons and outcomes in relation to ED visits by PEH.MethodsA protocol-led (CRD42020189263) systematic review was conducted using search of MEDLINE, EMBASE, CINAHL and Google Scholar databases. Studies that reported either the prevalence of homelessness in the ED or clinical reasons for presentation to ED by PEH and published in English language were included. Definitions of homelessness used by study authors were accepted.ResultsFrom the screening of 1349 unique titles, a total of 36 studies were included. Wide variations in the prevalence and key cause of presentations were identified across the studies often linked to differences in country, study setting, disease classification and data collection methods. The proportion of ED visits contributed by PEH ranged from 0.41 to 19.6%. PEH made an average of 0.72 visits to 5.8 visits per person per year in the ED [rate ratio compared to non-homeless 1.63 to 18.75]. Up to a third and quarter of the visits were contributed by alcohol-related diagnoses and substance poisoning respectively. The percentage of PEH who died in the ED ranged from 0.1 to 0.5%.ConclusionsDrug-, alcohol- and injury-related presentations dominate the ED visits by PEH. Wide variations in the data were observed in regard to attendance and treatment outcomes. There is a need for prevention actions in the community, integrated discharge and referral pathways between health, housing and social care to minimise frequent usage and improve attendance outcomes.

Severe mental illness (SMI; schizophrenia, bipolar disorders (BDs), and other nonorganic psychoses) is associated with increased risk of cardiovascular disease (CVD) and CVD-related mortality. To date, no systematic review has investigated changes in population level CVD-related mortality over calendar time. It is unclear if this relationship has changed over time in higher-income countries with changing treatments. To address this gap, a systematic review was conducted, to assess the association between SMI and CVD including temporal change. Seven databases were searched (last: November 30, 2021) for cohort or case-control studies lasting ≥1 year, comparing frequency of CVD mortality or incidence in high-income countries between people with versus without SMI. No language restrictions were applied. Random effects meta-analyses were conducted to compute pooled hazard ratios (HRs) and rate ratios, pooled standardised mortality ratios (SMRs), pooled odds ratios (ORs), and pooled risk ratios (RRs) of CVD in those with versus without SMI. Temporal trends were explored by decade. Subgroup analyses by age, sex, setting, world region, and study quality (Newcastle-Ottawa scale (NOS) score) were conducted. The narrative synthesis included 108 studies, and the quantitative synthesis 59 mortality studies (with (≥1,841,356 cases and 29,321,409 controls) and 28 incidence studies (≥401,909 cases and 14,372,146 controls). The risk of CVD-related mortality for people with SMI was higher than controls across most comparisons, except for total CVD-related mortality for BD and cerebrovascular accident (CVA) for mixed SMI. Estimated risks were larger for schizophrenia than BD. Pooled results ranged from SMR = 1.55 (95% confidence interval (CI): 1.33 to 1.81, p < 0.001), for CVA in people with BD to HR/rate ratio = 2.40 (95% CI: 2.25 to 2.55, p < 0.001) for CVA in schizophrenia. For schizophrenia and BD, SMRs and pooled HRs/rate ratios for CHD and CVD mortality were larger in studies with outcomes occurring during the 1990s and 2000s than earlier decades (1980s: SMR = 1.14, 95% CI: 0.57 to 2.30, p = 0.71; 2000s: SMR = 2.59, 95% CI: 1.93 to 3.47, p < 0.001 for schizophrenia and CHD) and in studies including people with younger age. The incidence of CVA, CVD events, and heart failure in SMI was higher than controls. Estimated risks for schizophrenia ranged from HR/rate ratio 1.25 (95% CI: 1.04 to 1.51, p = 0.016) for total CVD events to rate ratio 3.82 (95% CI: 3.1 to 4.71, p < 0.001) for heart failure. Incidence of CHD was higher in BD versus controls. However, for schizophrenia, CHD was elevated in higher-quality studies only. The HR/rate ratios for CVA and CHD were larger in studies with outcomes occurring after the 1990s. Study limitations include the high risk of bias of some studies as they drew a comparison cohort from general population rates and the fact that it was difficult to exclude studies that had overlapping populations, although attempts were made to minimise this. In this study, we found that SMI was associated with an approximate doubling in the rate ratio of CVD-related mortality, particularly since the 1990s, and in younger groups. SMI was also associated with increased incidence of CVA and CHD relative to control participants since the 1990s. More research is needed to clarify the association between SMI and CHD and ways to mitigate this risk.

Postpartum haemorrhage (excessive bleeding after birth) is a leading cause of maternal mortality and morbidity worldwide. However, there is no global consensus on which clinical markers best define excessive bleeding or reliably predict adverse maternal outcomes. The aim of this study was to assess the prognostic accuracy of clinical markers of postpartum bleeding in predicting maternal mortality or severe morbidity. In this individual participant data meta-analysis, eligible datasets were identified through a global call for data issued by WHO and systematic searches of PubMed, MEDLINE, Embase, the Cochrane Library, and WHO trial registries (from database inception to Nov 6, 2024). Studies were eligible if they included at least 200 participants with objectively measured blood loss or other clinical markers of haemodynamic instability, and reported at least one clinical outcome of interest. Individual participant data were requested for all eligible studies. For each dataset, we computed the prognostic accuracy of each clinical marker to predict a composite outcome of maternal mortality or severe morbidity (blood transfusion, surgical interventions, or admission to intensive care unit). Five clinical markers were assessed: measured blood loss, pulse rate, systolic blood pressure, diastolic blood pressure, and shock index. Results were meta-analysed through two-level mixed-effects logistic regression models, with a bivariate normal model used to generate summary accuracy estimates. Clinical marker and threshold selections were informed by a WHO expert consensus process, which placed emphasis on maximising prognostic sensitivity (preferably >80%) over prognostic specificity (preferably ≥50%). This meta-analysis was registered on PROSPERO (CRD420251034918). We identified 33 potentially eligible datasets and successfully obtained and analysed full data for 12 datasets, comprising 312 151 women. At the conventional threshold of 500 mL, measured blood loss had a summary prognostic sensitivity of 75·7% (95% CI 60·3–86·4) and specificity of 81·4% (95% CI 70·7–88·8) for predicting the composite outcome. The preferred sensitivity threshold was reached at 300 mL (83·9% [95% CI 72·8–91·1]), although at the expense of reduced specificity (54·8% [95% CI 38·0–70·5]). Prognostic performance improved with a decision rule that combined the use of either blood loss thresholds less than 500 mL (≥300 mL to ≥450 mL) and any abnormal haemodynamic sign (pulse rate >100 beats per min, systolic blood pressure <100 mm Hg, diastolic blood pressure <60 mm Hg, or shock index >1·0) or 500 mL or more of blood loss, with sensitivities ranging from 86·9% to 87·9% and specificities from 66·6% to 76·1%. Measured blood loss below the conventional threshold, combined with abnormal haemodynamic signs, accurately predicts women at risk of death or life-threatening complications from postpartum bleeding and could support earlier postpartum haemorrhage diagnosis and treatment. The Gates Foundation and UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction.

Background Type 1 diabetes is characterised by the immune-mediated destruction of pancreatic beta cells. We aimed to determine the effectiveness of immunotherapies for preserving residual beta cell function in newly diagnosed (stage 3) type 1 diabetes. Methods Searches were carried out in MEDLINE, Embase, Cochrane CENTRAL and trial registries until 31st Jul 2024. RCTs of immunotherapies to preserve beta cells in newly diagnosed type 1 diabetes were included. Data were extracted using a bespoke, piloted extraction sheet. Risk of bias was assessed using Cochrane Risk of Bias Tool 1. A random effects network meta-analysis was undertaken in R. The primary outcome was C-peptide. Interventions were analysed by class. Results Sixty trials were included (4597 patients, 32 intervention classes). Forty-one trials of 42 interventions were eligible for network meta-analysis. Eleven interventions demonstrated statistically significantly higher levels of C-peptide than placebo at 12 months, mesenchymal stem cells (autologous and Wharton’s jelly-derived cells), azathioprine, interferon-alpha (5000 IU), autologous dendritic cells, anti-TNF golimumab, low-dose ATG, 3 mg 1-course anti-CD3 teplizumab, baricitinib, cyclosporin and 9/11 mg 2-course anti-CD3 teplizumab but with substantial heterogeneity present ( I 2  = 66%). Azathioprine ranked highest (median ranking 3rd); however, rankings demonstrated relatively wide confidence intervals and thus uncertainty in exact rank order of near adjacent therapies. Risk of bias assessment identified poor reporting, particularly in older trials, but few studies demonstrated high risk overall. Conclusions Eleven of 42 interventions demonstrated statistically significantly higher C-peptide levels than placebo at 12 months in the network meta-analysis. These results have identified the 11 most promising therapies trialled and help to direct future head-to-head clinical trials to support approvals for interventions to treat those newly diagnosed with type 1 diabetes. However, data for some interventions originated from small studies (mesenchymal stem cell therapies, azathioprine, autologous dendritic cells) and findings should be considered as hypothesis generating and interpreted with caution due to evidence heterogeneity. Systematic review registration The protocol for the systematic review was registered on PROSPERO, the international database of prospectively registered systematic reviews (registration: CRD42018107904).

This study was aimed to evaluate the impact of community pharmacy (CP)-based medication therapy management (MTM) program on clinical and humanistic outcomes in patients with uncontrolled diabetes. An open label, parallel-group randomised controlled trial was undertaken at a community pharmacy in Riyadh city, Kingdom of Saudi Arabia. Patients with a diagnosis of uncontrolled diabetes (HbA1c of ≥ 8%) meeting the eligibility criteria were randomised to receive either the MTM programme provided by pharmacists or standard care. The primary outcome was change in HbA1c over 6 months. Secondary outcomes included: changes in clinical parameters (blood pressure (BP), lipid profile, serum creatinine (SCr) and albumin-to- creatinine ratio (ACR)), types of drug-related problems (DRPs), health service utilization (HSU), adherence, diabetes distress and overall patient satisfaction with the service at 6-month. A sufficiently powered sample of 160 participants with a mean age was 50 years (SD ± 11.9) was recruited. The majority of the patients (68.1%) were male and had diabetes for more than eight years [IQR 3, 14]. After adjusting for baseline HbA1c, compared to the control group, the mean HbA1c level was 0.02% ( p  = 0.929) and 0.2% ( p  = 0.47) lower in the intervention arm at 3-month and 6-month respectively. However, these differences were not statistically significant. Nonetheless, within each arm, there was a significant improvement in HbA1c from baseline. Furthermore, the intervention arm demonstrated improvement in BP control (SBP lowered by 3.2 mmHg (p = 0.05) and DBP lowered by 3.8 mmHg (p = 0.008)). During the study period, none of the participants in the intervention group reported hospitalization or ER visits compared to 14 patients in the control group [OR 0.069 (95% CI 0.004, 1.3)]. Patient satisfaction as measured by Patient Satisfaction with Pharmacist Services Questionnaire 2.0 (PSPSQ 2.0) was significantly higher among MTM program participants compared to standard care ( p  = 0.00001). Patients in the MTM program were eight times more likely to be adherent compared to the patients in the standard care [OR 7.89 (95% CI 3.6, 17.4)]. MTM program metrics showed that per patient, the pharmacists spent a median of 35 [IQR 30, 44.5] minutes at the initial visit and 20 [IQR 10, 25] minutes during the 6-month visit. The number of DRPs had significantly dropped in the intervention arm at 3 and 6-month (p = 0.0001). In conclusion, CP-based MTM program can improve health outcomes and prevent hospitalisations in patients with diabetes. These findings support the implementation of CP-based MTM services for patients with diabetes in the Kingdom of Saudi Arabia.

ObjectivesThis systematic review aims to evaluate externally validated models for individualised prediction of recurrence or survival in adults treated with curative intent for oropharyngeal cancer.DesignSystematic review.SettingHospital care.MethodsSystematic searches were conducted up to September 2023 and records were screened independently by at least two reviewers. The Prediction model Risk Of Bias ASsessment Tool was used to assess risk of bias (RoB). Model discrimination measures (c-indices) were presented in forest plots. Clinical and methodological heterogeneity precluded meta-analysis.ResultsFifteen studies developing and/or evaluating 25 individualised risk prediction models were included. The majority (77%) of c-indices for model developments and validations were ≥0.7 indicating ‘good’ discriminatory ability for models predicting overall survival. For disease-specific measures, most (73%) c-indices for model development were also ≥0.7, but fewer (40%) were ≥0.7 for external validations. Comparisons across models and outcome measures were hampered by heterogeneity. Only two studies directly compared models in the same cohort. Since all models were subject to a high RoB, primarily due to concerns with the analysis, the trustworthiness of the findings remains uncertain. Concerns included a lack of accounting for potentially missing data, model overfitting or competing risks as well as small event numbers. There were fewer concerns related to the participant, predictor and outcome domains, although reporting was not always detailed enough to make an informed decision. Where human papilloma virus (HPV) status and/or a radiomics score were included as a variable, models had better discriminative ability.ConclusionsThere were no models assessed as being at low RoB. Given that HPV status or a radiomics score appeared to improve model discriminative performance, further external validation of existing models to assess generalisability should focus on models that include HPV status as a variable. Development and validation of future models should be considered in HPV+ or HPV− cohorts separately to ensure representativeness.PROSPERO registration numberCRD42021248762.

Background Smoke from solid biomass cooking is often stated to reduce household mosquito levels and, therefore, malarial transmission. However, household air pollution (HAP) from solid biomass cooking is estimated to be responsible for 1.67 times more deaths in children aged under 5 years compared to malaria globally. This cross-sectional study investigates the association between malaria and (i) cleaner fuel usage; (ii) wood compared to charcoal fuel; and, (iii) household cooking location, among children aged under 5 years in sub-Saharan Africa (SSA). Methods Population-based data was obtained from Demographic and Health Surveys (DHS) for 85,263 children within 17 malaria-endemic sub-Saharan countries who were who were tested for malaria with a malarial rapid diagnostic test (RDT) or microscopy. To assess the independent association between malarial diagnosis (positive, negative), fuel type and cooking location (outdoor, indoor, attached to house), multivariable logistic regression was used, controlling for individual, household and contextual confounding factors. Results Household use of solid biomass fuels and kerosene cooking fuels was associated with a 57% increase in the odds ratio of malarial infection after adjusting for confounding factors (RDT adjusted odds ratio (AOR):1.57 [1.30–1.91]; Microscopy AOR: 1.58 [1.23–2.04]) compared to cooking with cleaner fuels. A similar effect was observed when comparing wood to charcoal among solid biomass fuel users (RDT AOR: 1.77 [1.54–2.04]; Microscopy AOR: 1.21 [1.08–1.37]). Cooking in a separate building was associated with a 26% reduction in the odds of malarial infection (RDT AOR: 0.74 [0.66–0.83]; Microscopy AOR: 0.75 [0.67–0.84]) compared to indoor cooking; however no association was observed with outdoor cooking. Similar effects were observed within a sub-analysis of malarial mesoendemic areas only. Conclusion Cleaner fuels and outdoor cooking practices associated with reduced smoke exposure were not observed to have an adverse effect upon malarial infection among children under 5 years in SSA. Further mixed-methods research will be required to further strengthen the evidence base concerning this risk paradigm and to support appropriate public health messaging in this context.

Recent studies suggest that chromosomal polymorphic variations are associated with infertility. A systematic review of chromosomal polymorphisms in assisted reproduction found an association with higher rates of miscarriage. Aim of this study is to analyse the influence of specific types or number of chromosomal polymorphic variations on reproductive outcomes of couples undergoing ICSI treatment. We analysed data from 929 fresh and frozen embryo transfer cycles of 692 women who underwent karyotyping analysis using Giemsa-Trypsin-Leishman (GTL) banding prior to the ICSI procedure at the Fertility Centre of Lanka Hospitals Corporation Plc, Sri Lanka, from January 2016 to December 2018. The outcomes of interest were the pregnancy, miscarriage and live birth rate per cycle. There was no evidence of a difference in the reproductive outcomes between carriers or non-carriers of any type or number of chromosomal polymorphic variation. Our data, in contrast to previous studies, does not support a deleterious effect for the type or number of chromosomal polymorphic variations on reproductive outcomes. However, additional prospective, adequately powered studies, conducted in multiethnic populations, are required to further investigate whether the detection of chromosomal polymorphic variants prior to assisted conception may in fact be a futile diagnostic tool.