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AbstractObjectiveTo compare the efficacy of covid-19 vaccines between immunocompromised and immunocompetent people.DesignSystematic review and meta-analysis.Data sourcesPubMed, Embase, Central Register of Controlled Trials, COVID-19 Open Research Dataset Challenge (CORD-19), and WHO covid-19 databases for studies published between 1 December 2020 and 5 November 2021. ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched in November 2021 to identify registered but as yet unpublished or ongoing studies.Study selectionProspective observational studies comparing the efficacy of covid-19 vaccination in immunocompromised and immunocompetent participants.MethodsA frequentist random effects meta-analysis was used to separately pool relative and absolute risks of seroconversion after the first and second doses of a covid-19 vaccine. Systematic review without meta-analysis of SARS-CoV-2 antibody titre levels was performed after first, second, and third vaccine doses and the seroconversion rate after a third dose. Risk of bias and certainty of evidence were assessed.Results82 studies were included in the meta-analysis. Of these studies, 77 (94%) used mRNA vaccines, 16 (20%) viral vector vaccines, and 4 (5%) inactivated whole virus vaccines. 63 studies were assessed to be at low risk of bias and 19 at moderate risk of bias. After one vaccine dose, seroconversion was about half as likely in patients with haematological cancers (risk ratio 0.40, 95% confidence interval 0.32 to 0.50, I2=80%; absolute risk 0.29, 95% confidence interval 0.20 to 0.40, I2=89%), immune mediated inflammatory disorders (0.53, 0.39 to 0.71, I2=89%; 0.29, 0.11 to 0.58, I2=97%), and solid cancers (0.55, 0.46 to 0.65, I2=78%; 0.44, 0.36 to 0.53, I2=84%) compared with immunocompetent controls, whereas organ transplant recipients were 16 times less likely to seroconvert (0.06, 0.04 to 0.09, I2=0%; 0.06, 0.04 to 0.08, I2=0%). After a second dose, seroconversion remained least likely in transplant recipients (0.39, 0.32 to 0.46, I2=92%; 0.35, 0.26 to 0.46), with only a third achieving seroconversion. Seroconversion was increasingly likely in patients with haematological cancers (0.63, 0.57 to 0.69, I2=88%; 0.62, 0.54 to 0.70, I2=90%), immune mediated inflammatory disorders (0.75, 0.69 to 0.82, I2=92%; 0.77, 0.66 to 0.85, I2=93%), and solid cancers (0.90, 0.88 to 0.93, I2=51%; 0.89, 0.86 to 0.91, I2=49%). Seroconversion was similar between people with HIV and immunocompetent controls (1.00, 0.98 to 1.01, I2=0%; 0.97, 0.83 to 1.00, I2=89%). Systematic review of 11 studies showed that a third dose of a covid-19 mRNA vaccine was associated with seroconversion among vaccine non-responders with solid cancers, haematological cancers, and immune mediated inflammatory disorders, although response was variable in transplant recipients and inadequately studied in people with HIV and those receiving non-mRNA vaccines.ConclusionSeroconversion rates after covid-19 vaccination were significantly lower in immunocompromised patients, especially organ transplant recipients. A second dose was associated with consistently improved seroconversion across all patient groups, albeit at a lower magnitude for organ transplant recipients. Targeted interventions for immunocompromised patients, including a third (booster) dose, should be performed.Systematic review registrationPROSPERO CRD42021272088.

Autoimmune diseases pose significant health challenges worldwide and affect millions. In recent years, there has been growing interest in exploring preventive strategies through nutritional interventions using vitamins, antioxidants, and micronutrients to reduce the risk of developing autoimmune diseases. However, excessive supplementation has also been associated with toxicity. We aim to assess how the intake of vitamins, antioxidants and micronutrients affect the risk of developing autoimmune diseases. This PRISMA-adherent systematic review involved a systematic search of PubMed, Embase and Cochrane for controlled studies that evaluated the risk of incident autoimmune diseases after supplementation. Random effects meta-analyses were used for primary analysis. 18 studies were included. Overall meta-analyses observed that vitamin D did not influence the risk of autoimmune diseases (RR=0.99, 95%CI: 0.81-1.20). However, among the different vitamin D dosages, subgroup analysis demonstrated that those who were supplemented with 600-800IU/day may have a statistically significant reduction in risk (RR=0.55, 95%CI: 0.38; 0.82). Systematic review suggested that consumption of most vitamins, micronutrients and antioxidants may not have any effect on the risk of autoimmune diseases. Smoking, age, physical or outdoor activity and diet were significant confounding factors that affected the efficacy of such interventions. We studied the effect of various vitamins, micronutrients and antioxidants on the risk of developing autoimmune diseases. Our study contributes to the evolving landscape of nutritional immunology, providing a foundation for future research to unravel more definite relationships with supplementation and the development of incident autoimmune diseases. https://www.crd.york.ac.uk/prospero/, identifier CRD42024504796.

Detecting interactions is a critical aspect of medical research. When interactions are present, it is essential to calculate confidence intervals for both the main effect and the interaction effect. This requires determining the covariance between the two effects. In a two-stage individual patient data (IPD) meta-analysis, the coefficients, as well as their variances and covariances, can be calculated for each study. These coefficients can then be combined into an overall estimate using either a fixed-effect or random-effects meta-analysis model. The overall variance of the combined coefficient is typically derived using the inverse-variance method. The most commonly used method for calculating the overall covariance between the main effect and the interaction effect in meta-analysis is multivariate meta-analysis. In this paper, we propose an alternative, straightforward, and transparent method for calculating this covariance when interactions are considered in a meta-analysis. To facilitate implementation, we have developed an R package, ‘covmeta’.

Clinical prediction models are commonly utilized in clinical practice to screen high-risk patients. This enables healthcare professionals to initiate interventions aimed at delaying or preventing adverse medical events. Nevertheless, the majority of these models focus on calculating probabilities or risk scores for medical events. This information can pose challenges for patients to comprehend, potentially causing delays in their treatment decision-making process. Our paper presents a statistical methodology and protocol for the utilization of a Weibull accelerated failure time (AFT) model in predicting the time until a health-related event occurs. While this prediction technique is widely employed in engineering reliability studies, it is rarely applied to medical predictions, particularly in the context of predicting survival time. Furthermore, we offer a practical demonstration of the implementation of this prediction method using a publicly available dataset.

Background: Recently, it has been discovered that anti-inflammatory and anti-oxidative pathways play a role in depression and anxiety. Lower serum levels of antioxidants, such as vitamin E, have been implicated in both depression and anxiety. Methods: This PROSPERO-registered systematic review (Reference: CRD42021260058) is reported according to PRISMA guidelines. PubMed, EMBASE, CENTRAL, PsycINFO, and CINAHL were searched from inception to June 2021. Results: Twelve studies were included in this systematic review, and nine in meta-analysis of vitamin E versus placebo. For depression, meta-analysis of 354 participants showed a standardised mean difference of –0.88 (95% CI: –1.54, –0.21; I2 = 87%) favouring vitamin E. For anxiety, meta-analysis of 306 participants showed a standardised mean difference of –0.86 (95% CI: –2.11, 0.40; I2 = 95%) favouring vitamin E. Three of the studies involved a pure comparison of vitamin E against placebo, while others included constituents such as omega-3 fatty acids. Nine of the studies were at low risk of bias, two had some concerns, and one was at high risk of bias. Conclusion: Vitamin E supplementation has shown inconclusive results in ameliorating both depression and anxiety. Containing a reassuring safety profile and low cost, future studies would be of promise, and they would benefit from both larger sample sizes and from excluding other constituents, such as omega-3 fatty acids, from experimental and comparator arms.

The UK observed a marked increase in scarlet fever and invasive group A streptococcal infection in 2022 with severe outcomes in children and similar trends worldwide. Here we report lineage M1 UK to be the dominant source of invasive infections in this upsurge. Compared with ancestral M1 global strains, invasive M1 UK strains exhibit reduced genomic diversity and fewer mutations in two-component regulator genes covRS . The emergence of M1 UK is dated to 2008. Following a bottleneck coinciding with the COVID-19 pandemic, three emergent M1 UK clades underwent rapid nationwide expansion, despite lack of detection in previous years. All M1 UK isolates thus-far sequenced globally have a phylogenetic origin in the UK, with dispersal of the new clades in Europe. While waning immunity may promote streptococcal epidemics, the genetic features of M1 UK point to a fitness advantage in pathogenicity, and a striking ability to persist through population bottlenecks. Exponential growth of toxigenic Streptococcus pyogenes M1 UK lineage accounted for most of the 2022/2023 invasive infection upsurge in the UK. Authors provide evidence that M1 UK first emerged in 2008, has genetic evidence of enhanced fitness, and has disseminated to 3 continents.

Abstract Context Diabetes mellitus is associated with morbid complications such as diabetic foot ulcers (DFUs) that may lead to amputations or mortality if not managed adequately. Objective New adjunctive interventions to treat diabetic wounds include topical biologics and growth factors. This study aims to evaluate their efficacy in improving wound-healing outcomes and safety. Methods Comprehensive database searches of MEDLINE via PubMed, EMBASE, and Cochrane were performed from inception to December 2022. Three independent researchers selected the studies. Randomized controlled trials that compared the use of a topical biologic growth factor-containing regimen to other biologics or standard of care (SOC) were included. This review followed PRISMA guidelines. Risk of bias analysis was performed using the Jadad scale. Network meta-analysis was performed. Treatments were grouped into common nodes based on the type of biologic agent. Primary outcomes of interest were healing rate and time to wound closure. Secondary outcomes included wound infection, serious adverse events (AEs), and amputation rate. Results Human umbilical cord (HUC) was associated with the highest cure, followed by recombinant human epidermal growth factor (hEGF). A significantly greater reduction in the time to cure DFUs was seen in HUC, hEGF, and fibroblast growth factor (FGF). There was a significantly lower risk of AEs when platelet-rich plasma (PRP) was administered. Conclusion HUC, hEGF, and FGF are promising topical biologics with statistically significant primary outcomes compared to SOC, while PRP is effective in reducing ulcer-related AEs. HUC has been found to be the most effective in terms of cure rate and a reduction in time to cure.

Background: Transcranial alternating current stimulation (TACS) is a non-invasive method of brain stimulation that is hypothesised to alter cortical excitability and brain electrical activity, modulating functional connectivity within the brain. Several trials have demonstrated its potential in treating psychiatric disorders such as depression and schizophrenia. Objectives: To study the efficacy of TACS in ameliorating symptoms of depression and schizophrenia in patients and its effects on cognition in patients and healthy subjects compared to sham stimulation. Design: Systematic review with meta-analysis. Data Sources and Methods: This PROSPERO-registered systematic review (CRD42022331149) is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, EMBASE, CENTRAL and PsycINFO were searched from inception to March 2022. Only randomised-controlled trials were included. Results: A total of 12 randomised-controlled trials are reviewed for meta-analysis, with three randomised-controlled trials reporting only effects on cognition in psychiatric and cognitively impaired patients, three trials on cognition in healthy subjects, one trial on cognition in both patients and healthy subjects, one trial on only depression, two on both cognition and depression in patients and two on schizophrenia symptoms. No studies were at significant risk of bias. For cognition, TACS showed significant improvement [positive standardised mean differences (SMD) denoting improvement] over sham stimulation in those with psychiatric disorders with an SMD of 0.60 (95% confidence interval [CI]: 0.14, 1.06). Similarly, among patients with depression, an SMD of 1.14 (95% CI: 0.10, 2.18) was found significantly favouring TACS over sham stimulation. Two studies assessed the effect of TACS on schizophrenia symptoms with mixed results. Conclusion: TACS has shown promise in ameliorating symptoms of both schizophrenia and depression in patients. TACS also improves cognition in both patients and healthy subjects. However, these findings are limited by the sample size of included studies, and future studies may be required to better our understanding of the potential of TACS. Registration: PROSPERO (CRD42022331149)

With advances in cancer diagnosis and therapy, survival after childhood and young-adult cancers has improved markedly. As survivorship extends, understanding long-term health sequelae, including obstetric outcomes, has become increasingly important. However, the reproductive safety of pregnancy following cancer remains insufficiently characterized. This systematic review and meta-analysis aims to provide a comprehensive evaluation of obstetric outcomes following pregnancy in survivors of childhood and young-adult cancers. We conducted a systematic review and meta-analysis (PROSPERO: CRD42024573707) of PubMed, Embase, and Cochrane databases to identify controlled studies assessing obstetric complications among female cancer survivors, published between 1 January 2000 and 31 June 2024. Random effects meta-analyses were used to estimate pooled risk ratios (RRs) with 95% confidence intervals (CIs). Heterogeneity, subgroup analyses, and meta-regression were performed to identify sources of variation. Of 6032 records screened, 16 studies involving 89,123 survivors and 21,569,191 controls were included. Cancer survivorship was associated with higher risks of preeclampsia (RR 1.37, 95% CI 1.17-1.62), gestational diabetes (RR 1.29, 95% CI 1.05-1.59), and miscarriage (RR 1.16, 95% CI 1.01-1.35), but not with anemia in pregnancy (RR 1.16, 95% CI 0.98-1.39) or hypertensive disorders (RR 1.21, 95% CI 0.99-1.49). Cancer type emerged as a potential prognostic factor for preeclampsia. Female cancer survivors are at significantly increased risk of major obstetric complications, underscoring the need for anticipatory preconception counselling and enhanced antenatal surveillance. Future research should delineate cancer- and treatment-specific risks to inform precision reproductive care in this growing survivorship population.

Introduction: Caffeine, in the form of coffee, tea and energy drinks, is recognised as the world’s most utilised psychoactive substance and consumed by approximately 80% of the global population daily. Emerging studies have suggested a more complex relationship in terms of the mental health outcomes that can arise after consumption. This is the first systematic review and meta-analysis that aims to explore the effects of caffeine consumption on the risk of suicide attempts, ideation and self-harm. Methods: This PRISMA-adherent systematic review involved a systematic search of PubMed, Embase, Cochrane and PsycINFO for all studies that evaluated the effects of caffeine consumption on the risk of suicide attempts, ideation and self-harm. Random effects meta-analyses and meta-regression were used for primary analysis. Results: Seventeen studies were included. The results demonstrated that coffee consumption of more than 60 cups per month significantly decreases the risk of suicide attempts. In contrast, energy drink consumption from as low as one cup per month was significantly associated with an increased risk of both suicide attempts and ideation. Meta-regression demonstrated a strong association between the dosage consumed and suicidality outcomes. Systematic review highlighted that male gender and substance usage significantly increased caffeine consumption. Conclusion: The results studied the associations between coffee and energy drink intake with suicide risk and suicidal ideation. Coffee intake was associated with reduced odds of suicide ideation and attempts, while consuming energy drinks was associated with an increased risk of both adverse outcomes. Further studies would be essential to elucidate the psychosocial factors and causative links underlying this association. Understanding the relationship between caffeine consumption and mental health outcomes is crucial to develop public health strategies to boost the mental health of consumers.