Is Type 2 Diabetes Mellitus Associated with Spinal Degenerative Disorders?: Evidence from Observational and 2-Sample Mendelian Randomization Analyses.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and spinal degenerative disorders (SDD) are common diseases that frequently coexist. However, both traditional observational studies and recent Mendelian randomization (MR) studies have demonstrated conflicting evidence on the association between T2DM and SDD. This comparative study explored and compared the association between T2DM and SDD using observational and MR analyses. METHODS: For observational analyses, cross-sectional studies (44,972 participants with T2DM and 403,095 participants without T2DM), case-control studies (38,234 participants with SDD and 409,833 participants without SDD), and prospective studies (35,550 participants with T2DM and 392,046 participants without T2DM with follow-up information until 2022) were performed to test the relationship between T2DM and SDD using individual-level data from the U.K. Biobank from 2006 to 2022. For MR analyses, the associations between single-nucleotide polymorphisms with SDD susceptibility obtained using participant data from the U.K. Biobank, which had 407,938 participants from 2006 to 2022, and the FinnGen Consortium, which had 227,388 participants from 2017 to 2022, and genetic predisposition to T2DM obtained using summary statistics from a pooled genome-wide association study involving 1,407,282 individuals were examined. The onset and severity of T2DM are not available in the databases being used. RESULTS: Participants with T2DM were more likely to have SDD than their counterparts. Logistic regression analysis identified T2DM as an independent risk factor for SDD, which was confirmed by the Cox proportional hazard model results. However, using single-nucleotide polymorphisms as instruments, the MR analyses demonstrated no causal relationship between T2DM and SDD. The lack of such an association was robust in the sensitivity analysis, and no pleiotropy was seen. CONCLUSIONS: Our results suggest that the association between T2DM and SDD may be method-dependent. Researchers and clinicians should be cautious in interpreting the association, especially the causal association, between T2DM and SDD. Our findings provide fresh insights into the association between T2DM and SDD by various analysis methods and guide future research and clinical efforts in the effective prevention and management of T2DM and SDD. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Comprehensive Observational and Longitudinal study on the Outbreak of Stroke-related Spasticity focusing on the Early Onset management with Botulinum NeuroToxin (COLOSSEO-BoNT): protocol for a real-world prospective observational study on upper limb spasticity.

INTRODUCTION: Poststroke spasticity (PSS) affects up to 40% of patients who had a stroke. Botulinum neurotoxin type A (BoNT-A) has been shown to improve spasticity, but the optimal timing of its application remains unclear. While several predictors of upper limb PSS are known, their utility in clinical practice in relation to BoNT-A treatment has yet to be fully elucidated. The COLOSSEO-BoNT study aims to investigate predictors of PSS and the effects of BoNT-A timing on spasticity-related metrics in a real-world setting. METHODS AND ANALYSIS: The recruitment will involve approximately 960 patients who have recently experienced an ischaemic stroke (within 10 days, V0) and will follow them up for 24 months. Parameters will be gathered at specific intervals: (V1) 4, (V2) 8, (V3) 12, (V4) 18 months and (V5) 24 months following enrolment. Patients will be monitored throughout their rehabilitation and outpatient clinic journeys and will be compared based on their BoNT-A treatment status-distinguishing between patients receiving treatment at different timings and those who undergo rehabilitation without treatment. Potential predictors will encompass the Fugl-Meyer assessment, the National Institute of Health Stroke Scale (NIHSS), stroke radiological characteristics, performance status, therapies and access to patient care pathways. Outcomes will evaluate muscle stiffness using the modified Ashworth scale and passive range of motion, along with measures of quality of life, pain, and functionality. ETHICS AND DISSEMINATION: This study underwent review and approval by the Ethics Committee of the Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy. Regardless of the outcome, the findings will be disseminated through publication in peer-reviewed journals and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT05379413.

Impact of dietary inflammatory index on gestational diabetes mellitus in normal and overweight women: a systematic review and meta-analysis of observational studies.

BACKGROUND AND OBJECTIVES: To systematically investigate the association between the dietary inflammatory index (DII) and gestational diabetes mellitus (GDM), with a focus on the role of BMI in this relationship. METHODS AND STUDY DESIGN: A comprehensive search was conducted in PubMed, Embase, Web of Science, The Cochrane Library, Medline, CINAHL Complete, Chinese Periodical Full-text Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and China Wanfang Database for rele-vant observational studies published up to August 2023. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. The pooled effect size was calculated using a random-effects model. Sub-group and meta-regression analyses were performed to explore potential sources of heterogeneity. RESULTS: The study included 54,058 participants from 10 studies. Pregnant women with a higher DII, indicating a pro-inflammatory diet, had a significantly increased risk of GDM compared to those with a lower DII, indicating an anti-inflammatory diet (pooled OR: 1.17, 95% CI: 1.01-1.36; I²=70%, p <0.001). Subgroup analyses revealed a stronger association in normal weight stratification (OR: 1.25, 95%CI: 1.04-1.51), case-control studies (OR: 1.45, 95%CI: 1.03-2.05), Asia (OR: 1.26, 95%CI: 1.10-1.43), Europe (OR: 1.27, 95%CI: 1.09-1.48), 3-day dietary record as a dietary assessment tool (OR: 1.30, 95%CI: 1.16-1.46), physical activity adjustment (OR: 1.28, 95%CI: 1.13-1.46), and energy intake adjustment (OR: 1.33, 95%CI: 1.19-1.48). Meta-regression analysis confirmed that geographical region significantly influenced heterogeneity between studies (p <0.05). CONCLUSIONS: An elevated DII is independently linked to a higher risk of GDM, especially in women of normal weight.

Health Outcomes around Pregnancy and Exposure to HIV/Antiretrovirals (HOPE) study protocol: a prospective observational cohort study of reproductive-aged women living with HIV.

INTRODUCTION: Over 265 000 women are living with HIV in the USA, but limited research has investigated the physical, mental and behavioural health outcomes among women living with HIV of reproductive age. Health status during the reproductive years before, during and after pregnancy affects pregnancy outcomes and long-term health. Understanding health outcomes among women living with HIV of reproductive age is of substantial public health importance, regardless of whether they experience pregnancy. The Health Outcomes around Pregnancy and Exposure to HIV/Antiretrovirals (HOPE) study is a prospective observational cohort study designed to investigate physical and mental health outcomes of young women living with HIV as they age, including HIV disease course, engagement in care, reproductive health and choices and cardiometabolic health. We describe the HOPE study design, and characteristics of the first 437 participants enrolled as of 1 January 2024. METHODS AND ANALYSIS: The HOPE study seeks to enrol and follow 1630 women living with HIV of reproductive age, including those with perinatally-acquired HIV, at 12 clinical sites across 9 US states and Puerto Rico. HOPE studies multilevel dynamic determinants influencing physical, mental and social well-being and behaviours of women living with HIV across the reproductive life course (preconception, pregnancy, post partum, not or never-pregnant), informed by the socioecological model. Key research areas include the clinical course of HIV, relationship of HIV and antiretroviral medications to reproductive health, pregnancy outcomes and comorbidities and the influence of racism and social determinants of health. HOPE began enrolling in April 2022. ETHICS AND DISSEMINATION: The HOPE study received approval from the Harvard Longwood Campus Institutional Review Board, the single institutional review board of record for all HOPE sites. Results will be disseminated through conference presentations, peer-reviewed journals and lay summaries.

Effectiveness of Sodium-Glucose Cotransporter 2 Inhibitors in Patients With Acute Myocardial Infarction With or Without Type 2 Diabetes: A Systematic Review and Meta-analysis.

ABSTRACT: Recent studies have revealed the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in heart failure patients. However, their effects on acute myocardial infarction (AMI) remain uncertain. Therefore, we conducted this meta-analysis to assess the effectiveness of SGLT2i in patients with AMI with or without diabetes. We conducted a comprehensive search of PubMed, Embase, and Cochrane Library encompassing data from inception until November 30, 2023. Relevant studies comparing SGLT2i with placebo or non-SGLT2i in patients with AMI were included. The mean difference and/or odds ratio (OR) with 95% confidence intervals were pooled using a fixed-effects model when the heterogeneity statistic (I2) was less than 50%; otherwise, a random-effects model was employed. Four randomized controlled trials and 4 observational studies involving 9397 patients with AMI were included in this meta-analysis. Patients treated with SGLT2i exhibited a significantly lower rate of hospitalization for heart failure (OR = 0.50, 95% CI: 0.32-0.80) and all-cause death (OR = 0.65, 95% CI: 0.44-0.95) compared with those treated with placebo or non-SGLT2i. Furthermore, the use of SGLT2i was associated with a significant increase in left ventricular ejection fraction (mean difference = 1.90, 95% CI: 1.62-2.17) and a greater reduction of N-terminal prohormone of brain natriuretic peptide (OR = 0.88, 95% CI 0.82-0.94). Subgroup analysis revealed that in patients with diabetes, SGLT2i exhibited similar effects. The present meta-analysis provided evidence indicating the effectiveness of SGLT2i in patients with AMI; SGLT2i may serve as an additional therapeutic option for patients with AMI, regardless of the presence or absence of diabetes.

The efficacy of topical oxygen therapy for wound healing: A meta-analysis of randomized controlled trials and observational studies.

In preclinical studies, topical oxygen treatment (TOT) was shown to enhance wound healing by applying supplemental oxygen topically to the surface of a moist wound at normobaric conditions. The objective of this systematic review and meta-analysis is to provide a thorough evaluation of published RCTs and observational studies that compare supplemental TOT with standard wound care. A total of 1077 studies were obtained from a variety of databases, including PubMed, ScienceDirect, Web of Science, ProQuest, Scopus, ClinicalTrials.gov, EU Clinical Trial Registers, and Preprints.org. The Jadad scale was employed to assess the reliability of RCT studies, while the Newcastle-Ottawa Scale (NOS) was employed to assess the quality of observational studies. Seven RCT studies (n = 692) and two controlled observational studies (n = 111) were analysed. The rate of healed wounds was 25.8% in the control group and 43.25% in the adjuvant TOT group, which shows the use of TOT significantly increased the number of healed wounds (RR = 1.77; 95% CI 1.18-2.64; p = 0.005). A significant decrease in the percentage of wound area was found in the TOT group in RCT studies (mean difference = 15.64; 95% CI 5.22-26.06; p = 0.003). In observational studies, the rate of healed wounds was 37.5% in the standard care group and 80.95% in the adjuvant TOT group, which shows a significant increase in the number of healed wounds in the adjuvant TOT group (RR = 2.15; 95% CI 1.46-3.15; p < 0.00001). Topical oxygen therapy is considered a great adjuvant therapy for chronic wound healing, particularly wounds with vascular compromise such as diabetic ulcers and pressure ulcers. Further studies on this topic are still needed as there are a lot of potential uses for this technology in various types of wounds.

Adherence to Mediterranean dietary pattern and the risk of gestational diabetes mellitus: a systematic review and meta-analysis of observational studies.

BACKGROUND AND AIM: Gestational diabetes mellitus (GDM) is one of the most prevalent disorders occurring during pregnancy, which confers significant risk of short and long-term adverse outcomes in both mothers and offspring. Recently, more attention has been paid to the association of pre-pregnancy and early pregnancy healthy dietary patterns, such as Mediterranean dietary pattern with GDM. However, there is a lack of systematic review and meta-analysis summarizing findings in this regard. Hence, we sought to assess the association of MedDiet and GDM in observational studies by performing a systematic review and meta-analysis. METHODS: A comprehensive systematic literature search of observational studies was conducted via PubMed, Scopus, and Google Scholar, up to August 2023. Studies were included in our review if they evaluated the association of MedDiet and GDM, following an observational study design. RESULTS: Ten studies were included in this study. Combining effect sizes, we found that adherence to MedDiet was inversely associated with GDM risk (OR = 0.64; CI: 0.52-0.78); implying that higher adherence to the MedDiet could reduce the risk of GDM by about 36%. Stratification by the geographic area, Mediterranean countries, time of dietary assessment and study design, showed a consistent significant association between MedDiet and GDM. CONCLUSION: We conclude that adhering to diets resembling MedDiet, before or in early pregnancy, could be associated with lower risks or odds of GDM.

Bias due to coarsening of time intervals in the inference for the effectiveness of colorectal cancer screening.

BACKGROUND: Observational studies are frequently used to estimate the comparative effectiveness of different colorectal cancer (CRC) screening methods due to the practical limitations and time needed to conduct large clinical trials. However, time-varying confounders, e.g. polyp detection in the last screening, can bias statistical results. Recently, generalized methods, or G-methods, have been used for the analysis of observational studies of CRC screening, given their ability to account for such time-varying confounders. Discretization, or the process of converting continuous functions into discrete counterparts, is required for G-methods when the treatment and outcomes are assessed at a continuous scale. DEVELOPMENT: This paper evaluates the interplay between time-varying confounding and discretization, which can induce bias in assessing screening effectiveness. We investigate this bias in evaluating the effect of different CRC screening methods that differ from each other in typical screening frequency. APPLICATION: First, using theory, we establish the direction of the bias. Then, we use simulations of hypothetical settings to study the bias magnitude for varying levels of discretization, frequency of screening and length of the study period. We develop a method to assess possible bias due to coarsening in simulated situations. CONCLUSIONS: The proposed method can inform future studies of screening effectiveness, especially for CRC, by determining the choice of interval lengths where data are discretized to minimize bias due to coarsening while balancing computational costs.

Efficacy and Safety of Azvudine in Patients With COVID-19 in China: A Meta-Analysis of Observational Studies.

BACKGROUND: Azvudine (FNC) is a novel small molecule antiviral drug for treating COVID-19 that is available only on the Chinese market. Despite being recommended for treating COVID-19 by the Chinese guidelines, its efficacy and safety are still unclear. This study aimed to evaluate the protective effect of FNC on COVID-19 outcomes and its safety. METHODS: We followed the PRISMA 2020 guidelines and searched the PubMed, Embase, Web of Science, Scopus, and China National Knowledge Infrastructure (CNKI) databases to evaluate studies on the effectiveness of FNC in treating COVID-19 in China, focusing on mortality and overall outcomes. Additionally, its impact on the length of hospital stay (LOHS), time to first nucleic acid negative conversion (T-FNANC), and adverse events was evaluated. The inclusion criterion was that the studies were published from July 2021 to April 10, 2024. This study uses the ROBINS-I tool to assess bias risk and employs the GRADE approach to evaluate the certainty of the evidence. RESULTS: The meta-analysis included 24 retrospective studies involving a total of 11 830 patients. Low-certainty evidence revealed no significant difference in mortality (OR = 0.91, 95% CI: 0.76-1.08) or LOHS (WMD = -0.24, 95% CI: -0.83 to 0.35) between FNC and Paxlovid in COVID-19 patients. Low-certainty evidence shows that the T-FNANC was longer (WMD = 1.95, 95% CI: 0.36-3.53). Compared with the Paxlovid group, low-certainty evidence shows the FNC group exhibited a worse composite outcome (OR = 0.77, 95% CI: 0.63-0.95) and fewer adverse events (OR = 0.63, 95% CI: 0.46-0.85). Compared with supportive treatment, low certainty shows FNC significantly reduced the mortality rate in COVID-19 patients (OR = 0.61, 95% CI: 0.51-0.74) and decreased the composite outcome (OR = 0.67, 95% CI: 0.50-0.91), and very low certainty evidence shows significantly decreased the T-FNANC (WMD = -4.62, 95% CI: -8.08 to -1.15). However, in very low certainty, there was no significant difference in LOHS (WMD = -0.70, 95% CI: -3.32 to 1.91) or adverse events (OR = 1.97, 95% CI: 0.48-8.17). CONCLUSIONS: FNC appears to be a safe and potentially effective treatment for COVID-19 in China, but further research with larger, high-quality studies is necessary to confirm these findings. Due to the certainty of the evidence and the specific context of the studies conducted in China, caution should be exercised when considering whether the results are applicable worldwide. TRIAL REGISTRATION: PROSPERO number: CRD42024520565.

Real-world evidence of early rhythm control in patients with atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: The favorable benefits of early rhythm control (ERC) therapy in newly diagnosed patients with atrial fibrillation (AF) have been demonstrated in the EAST-AFNET 4 trial. However, the generalizability and applicability of ERC in real-world clinical settings remain inconclusive. METHODS: We conducted a systematic search of the PubMed and Embase databases to identify observational studies published between January 2020 and February 2024 that focused on real-world evidence pertaining to ERC. The effectiveness and safety outcomes in our study were analogous to those evaluated in the EAST-AFNET 4 trial. RESULTS: A total of 4 observational studies that fulfilled the inclusion criteria of EAST-AFNET 4 were included, involving 130,970 patients with AF, 30.7% of whom received ERC therapy. In our pooled analysis using the fixed-effects model, compared with rate control, ERC significantly decreased the occurrence risk of the primary composite outcome (hazard ratio [HR] 0.86, 95% confidence interval[CI] 0.82-0.91), cardiovascular death (HR 0.87, 95% CI 0.78-0.98), stroke (HR 0.80, 95% CI 0.73-0.87), and hospitalization with worsening heart failure (HR 0.91, 95% CI 0.84-0.99) or acute coronary syndrome (HR 0.72, 95% CI 0.59-0.87). In terms of safety outcomes, there were no differences in the composite safety outcome (HR 1.00, 95% CI 0.95-1.05) and all-cause death (HR 0.93, 95% CI 0.82-1.06) between the two studied groups. CONCLUSIONS: ERC therapy showed favorable effectiveness outcomes compared with rate control, whereas the safety outcomes between the two therapeutic strategies did not differ significantly, supporting the benefits of ERC therapy over rate control in selected real-world patients with AF. REGISTRATION: The study protocol was registered to PROSPERO (CRD42023443569).

Rationale, Design, and Baseline Characteristics of Participants in the Health@NUS mHealth Augmented Cohort Study Examining Student-to-Work Life Transition: Protocol for a Prospective Cohort Study.

BACKGROUND: Integration of mobile health data collection methods into cohort studies enables the collection of intensive longitudinal information, which gives deeper insights into individuals' health and lifestyle behavioral patterns over time, as compared to traditional cohort methods with less frequent data collection. These findings can then fill the gaps that remain in understanding how various lifestyle behaviors interact as students graduate from university and seek employment (student-to-work life transition), where the inability to adapt quickly to a changing environment greatly affects the mental well-being of young adults. OBJECTIVE: This paper aims to provide an overview of the study methodology and baseline characteristics of participants in Health@NUS, a longitudinal study leveraging mobile health to examine the trajectories of health behaviors, physical health, and well-being, and their diverse determinants, for young adults during the student-to-work life transition. METHODS: University students were recruited between August 2020 and June 2022 in Singapore. Participants would complete biometric assessments and questionnaires at 3 time points (baseline, 12-, and 24-month follow-up visits) and use a Fitbit smartwatch and smartphone app to continuously collect physical activity, sedentary behavior, sleep, and dietary data over the 2 years. Additionally, up to 12 two-week-long bursts of app-based ecological momentary surveys capturing lifestyle behaviors and well-being would be sent out among the 3 time points. RESULTS: Interested participants (n=1556) were screened for eligibility, and 776 participants were enrolled in the study between August 2020 and June 2022. Participants were mostly female (441/776, 56.8%), of Chinese ethnicity (741/776, 92%), undergraduate students (759/776, 97.8%), and had a mean BMI of 21.9 (SD 3.3) kg/m2, and a mean age of 22.7 (SD 1.7) years. A substantial proportion were overweight (202/776, 26.1%) or obese (42/776, 5.4%), had indicated poor mental well-being (World Health Organization-5 Well-Being Index ≤50; 291/776, 37.7%), or were at higher risk for psychological distress (Kessler Psychological Distress Scale ≥13; 109/776, 14.1%). CONCLUSIONS: The findings from this study will provide detailed insights into the determinants and trajectories of health behaviors, health, and well-being during the student-to-work life transition experienced by young adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT05154227; https://clinicaltrials.gov/study/NCT05154227. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56749.

Hypothesis testing and sample size considerations for the test-negative design.

The test-negative design (TND) is an observational study design to evaluate vaccine effectiveness (VE) that enrolls individuals receiving diagnostic testing for a target disease as part of routine care. VE is estimated as one minus the adjusted odds ratio of testing positive versus negative comparing vaccinated and unvaccinated patients. Although the TND is related to case-control studies, it is distinct in that the ratio of test-positive cases to test-negative controls is not typically pre-specified. For both types of studies, sparse cells are common when vaccines are highly effective. We consider the implications of these features on power for the TND. We use simulation studies to explore three hypothesis-testing procedures and associated sample size calculations for case-control and TND studies. These tests, all based on a simple logistic regression model, are a standard Wald test, a continuity-corrected Wald test, and a score test. The Wald test performs poorly in both case-control and TND when VE is high because the number of vaccinated test-positive cases can be low or zero. Continuity corrections help to stabilize the variance but induce bias. We observe superior performance with the score test as the variance is pooled under the null hypothesis of no group differences. We recommend using a score-based approach to design and analyze both case-control and TND. We propose a modification to the TND score sample size to account for additional variability in the ratio of controls over cases. This work enhances our understanding of the data generating mechanism in a test-negative design (TND) and how it is distinct from that of a case-control study due to its passive recruitment of controls.

Adverse cardiovascular outcomes associated with proton pump inhibitor use after percutaneous coronary intervention: a systematic review and meta-analysis.

BACKGROUND: Proton pump inhibitors (PPIs) are commonly prescribed for gastroprotection in patients undergoing percutaneous coronary intervention (PCI), who are at increased risk of gastrointestinal bleeding due to antiplatelet therapy. However, emerging evidence suggests that PPIs may adversely impact cardiovascular outcomes. This systematic review and meta-analysis sought to assess the relationship between using PPIs and cardiovascular outcomes in patients following PCI. METHODS: We searched various databases up to March 15, 2024, for observational studies and randomized controlled trials (RCTs) assessing the cardiovascular effects of PPIs in PCI patients. Data were extracted on study characteristics, patient demographics, PPI use, and cardiovascular outcomes. The Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool 2 assessed study quality. Meta-analyses were conducted using a random-effects model using R software version 4.3. RESULTS: A total of 21 studies involving diverse populations and study designs were included. Observational studies suggested a moderate increase in risk for composite cardiovascular diseases (CVD), myocardial infarction (MI), and major adverse cardiac events (MACE) associated with PPI use, with pooled hazard ratios (HRs) of 1.20 (95% CI: 1.093-1.308) for CVD, 1.186 (95% CI: 1.069-1.303) for MI, and 1.155 (95% CI: 1.001-1.309) for MACE. However, RCTs showed no significant link between PPI therapy and negative cardiovascular events (Relative Risk: 1.016, 95% CI: 0.878-1.175). Substantial heterogeneity was observed among observational studies but not RCTs. CONCLUSION: The findings indicate that while observational studies suggest a potential risk of adverse cardiovascular events with post-PCI use of PPI, RCTs do not support this association. Further large-scale, high-quality studies are required to understand the cardiovascular implications of individual PPIs better and optimize patient management post-PCI. This analysis shows the complexity of PPI use in patients with coronary artery diseases and the necessity to balance gastroprotective benefits against potential cardiovascular risks.

Waiving the consent requirement to mitigate bias in observational precision medicine research.

Consent bias is a type of selection bias in biomedical research where those consenting to the research differ systematically from those not consenting. It is particularly relevant in precision medicine research because the complexity of these studies prevents certain subgroups from understanding, trusting, and consenting to the research. Because consent bias distorts research findings and causes inequitable distribution of research benefits, scholars propose two types of schemes to reduce consent bias: reforming existing consent models and removing the consent requirement altogether. This study explores the possibility of waiving consent in observational studies using existing data, because they involve fewer risks to participants than clinical trials if privacy safeguards are strengthened. It suggests that data protection mechanisms such as security enhancement and data protection impact assessment should be conducted to protect data privacy of participants in observational studies without consent.

Long-term trajectories of weight loss and health outcomes: protocol of the SCOOP-RNPC nationwide observational study.

INTRODUCTION: Behavioural weight loss programmes are generally accepted as being beneficial in reducing cardiometabolic risk and improving patient-reported outcomes. However, prospective data from large real-world cohorts are scarce concerning the mid-term and long-term impact of such interventions. The objective of this large prospective cohort study (n>10 000 participants) is to demonstrate the effectiveness of the standardised Nutritional and Psycho-Behavioural Rehabilitation programme (RNPC Programme) in reducing the percentage of subjects requiring insulin and/or other diabetes drug therapy, antihypertensive drugs, lipid-lowering therapies and continuous positive airway pressure therapy for obstructive sleep apnoea after the end of the intervention. The rate of remission of hypertension, type 2 diabetes and sleep apnoea will also be prospectively assessed. METHODS: This is a prospective multicentre observational study carried out in 92 RNPC centres in France. Participants will follow the standardised RNPC Programme. The prospective dataset will include clinical, anthropometric and biochemical data, comorbidities, medications, body composition, patient-reported outcome questionnaire responses, sleep study data with objective measurements of sleep apnoea severity and surrogate markers of cardiovascular risk (ie, blood pressure and arterial stiffness). About 10 000 overweight or obese participants will be included over 2 years with a follow-up duration of up to 5 years. ETHICS AND DISSEMINATION: Ethical approval for this study has been granted by the Ethics Committee (Comité de protection des personnes Sud-Est I) of Saint-Etienne University Hospital, France (SI number: 23.00174.000237). Results will be submitted for publication in peer-review journals, presented at conferences and inform the design of a future randomised controlled trial in the specific population identified as good responders to the RNPC Programme. TRIAL REGISTRATION NUMBER: NCT05857319.

Real-world effectiveness of belimumab in patients with lupus in China: RELIABLE observational cohort study protocol.

INTRODUCTION: The efficacy of belimumab in SLE has been demonstrated in randomised clinical trials, and its real-world effectiveness has been shown in studies in several countries. While belimumab was approved for treating SLE in China in 2019, data on its benefit in clinical practice are limited. This study will evaluate belimumab's effectiveness in China, using practical clinical measures, such as Lupus Low Disease Activity State (LLDAS), to add to the body of real-world evidence. METHODS AND ANALYSIS: The Real-world Effectiveness of beLImumAB in patients with systemic Lupus Erythematosus in China (RELIABLE) is an ambidirectional, observational descriptive cohort study across approximately 15 centres in China. Adults with SLE newly initiating belimumab with ≥1 measure of all five LLDAS components (SLE Disease Activity Index-2000; no new lupus disease activity; Physician Global Assessment; prednisolone-equivalent dose; immunosuppressants/biologics use) in the 3 months preceding belimumab initiation (index date) will be eligible and retrospectively and/or prospectively enrolled, depending on data availability. The retrospective follow-up will be ≤6 months, and retrospective and prospective patients will have a maximum 24-month follow-up. The primary objectives will be to describe the proportion of patients achieving LLDAS at 12 and 24 months post-index. The key secondary objective will be to describe the proportion of patients achieving LLDAS and each component at 3, 6, 9 and 18 months post-index. All data will be analysed descriptively; a statistical estimand will be applied to account for intercurrent events expected in a real-world setting. ETHICS AND DISSEMINATION: This study will comply with all applicable laws regarding patient privacy; institutional review board approval will be obtained before the study commencement. CONCLUSIONS: This study will evaluate belimumab's effectiveness in patients with SLE initiating belimumab in clinical practice in China. Using LLDAS will provide clinicians with valuable insights into the impact of belimumab on the treat-to-target strategy with a relevant measure that can be repeated across the clinical practice.

Multiply robust estimation of marginal structural models in observational studies subject to covariate-driven observations.

Electronic health records and other sources of observational data are increasingly used for drawing causal inferences. The estimation of a causal effect using these data not meant for research purposes is subject to confounding and irregularly-spaced covariate-driven observation times affecting the inference. A doubly-weighted estimator accounting for these features has previously been proposed that relies on the correct specification of two nuisance models used for the weights. In this work, we propose a novel consistent multiply robust estimator and demonstrate analytically and in comprehensive simulation studies that it is more flexible and more efficient than the only alternative estimator proposed for the same setting. It is further applied to data from the Add Health study in the United States to estimate the causal effect of therapy counseling on alcohol consumption in American adolescents.

Factors associated with sarcopenic obesity in Brazilian adults and older people: Systematic review and meta-analysis of observational studies.

AIM: Sarcopenic obesity (SO) is characterized by the coexistence of the loss of muscle mass and function with excess adipose tissue. Its prevalence has increased concomitantly with population aging, becoming one of the most significant challenges for public health, threatening the quality of life and the physical and mental health of the elderly population. METHODS: This study estimated the prevalence and factors associated with SO among adults and the elderly in Brazil's macro-regions, utilizing MEDLINE, Embase, Web of Science, and the Virtual Health Library databases. Primary outcomes included SO prevalence overall and by subgroups, with secondary outcomes identifying associated factors. RESULTS: A systematic review of 33 studies with 10 266 participants up to July 2023 showed a 17% prevalence of SO (95% confidence interval: 13-21%), using a random effects meta-analysis. The Central-West region had the highest occurrence (27%). Dual-energy X-ray absorptiometry (26%) and bioimpedance (6%) were the top diagnostic methods. Protective factors were chronic kidney disease and healthy lifestyles; risk factors included socioeconomic status, functionality, lifestyle, biochemical parameters, and comorbidities such as osteoarthritis and apnea. CONCLUSIONS: The prevalence of SO in Brazil is significant, emerging as a critical public health problem. It is essential to direct attention to changes in prevalence rates in the coming years, given the rising obesity trends and the absolute increase in the elderly population. Geriatr Gerontol Int 2024; 24: 661-674.