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Objective: This study aimed to evaluate the degrees of dependence and presence of bacterial plaque in children with autism spectrum disorder (ASD) and the quality of life of children and their caregivers. Method and materials: This was a cross-sectional observational study. This study included 119 individuals with ASD and their caregivers. Data were collected through a sociodemographic questionnaire, WHOQOL-Bref, and Burden interview to measure quality of life and caregiver burden, respectively. The Autoquestionnaire Qualité de Vie Enfant Imagé questionnaire, adapted in game format, was applied to verify quality of life in children with ASD. An oral clinical examination evaluated the visible plaque index. The collected data were tabulated and organized for statistical analysis with a significance level of 5%. Results: It was observed that 52% of the children had a severity of ASD level 1; 70% were dependent for general activities, and 65% were dependent for oral hygiene. Of the 77 children who thoroughly answered the questionnaire about their quality of life, 64.9% had good quality of life, and 35.1% had scores below 48, that is, low quality of life. In general, the caregivers generally presented quality of life with a rate of 60.95 (good) points on the scale. It was observed that gingival bleeding greater than 30% is two (ASD 2 + ASD 3) to three (ASD 3) times more likely to occur in patients who have higher levels of ASD (P < .004). Conclusion: It was concluded that the quality of life of individuals with ASD was good, that most children are dependent for their daily activities and oral hygiene, and that they showed reasonable plaque control. On the other hand, the caregivers presented low quality of life and moderate burden. [ABSTRACT FROM AUTHOR]

Background: Weakness of the shoulder girdle muscles has been reported in patients with chronic lateral elbow tendinopathy. The aim of this study was to assess the short- and long-term effects of a conventional treatment plus scapular exercises program in patients with chronic lateral elbow tendinopathy. Methods: A single-group prestudy and poststudy were conducted. The primary outcome was the Patient-Rated Tennis Elbow Evaluation questionnaire score. Secondary outcomes were grip strength; Disabilities of the Arm, Shoulder, and Hand questionnaire score; Visual Analogue Scale score at rest and at grip, and presence of scapular dyskinesis. Results: A total of 65 patients (72.3% females), with a mean age of 41.8 years, were analyzed. At the end of 6 weeks, the results showed clinically and statistically significant differences (P< .05). At 1-year follow-up, the differences were: Patient-Rated Tennis Elbow Evaluation -31 points (P<.001); grip strength +33.6% (P<.001); Disabilities of the Arm, Shoulder, and Hand -34.2 points (P < .001); Visual Analogue Scale at rest -2.5 cm (P < .001); and Visual Analogue Scale at grip -2.3 cm (P < .001). Conclusion: At the end of 6 weeks and at 1-year follow-up, conventional treatment plus scapular exercises program showed statistically and clinically significant differences in all functional outcomes assessed in patients with lateral elbow tendinopathy. [ABSTRACT FROM AUTHOR]

We explore one systematic review and meta-analysis of both observational and randomized studies examining COVID-19 vaccines in 5- to 11-year-olds, which reported substantial benefits associated with vaccinating this age group. We discuss the limitations of the individual studies that were used to estimate vaccination benefits. The review included five observational studies that evaluated vaccine effectiveness (VE) against COVID-19 severe disease or hospitalization. All five studies failed to adequately assess differences in underlying health between vaccination groups. In terms of vaccination harms, looking only at the randomized studies, a significantly higher odds of adverse events was identified among the vaccinated compared with the unvaccinated. Observational studies are at risk of overestimating the effectiveness of vaccines against severe disease if healthy vaccinee bias is present. Falsification endpoints can provide valuable information about underlying healthy vaccinee bias. Studies that have not adequately ruled out bias due to better health among the vaccinated or more vaccinated should be viewed as unreliable for estimating the VE of COVID-19 vaccination against severe disease and mortality. Existing systematic reviews that include observational studies of the COVID-19 vaccine in children may have overstated or falsely inferred vaccine benefits due to unidentified or undisclosed healthy vaccinee bias.

INTRODUCTION: Optimal venous thromboembolism (VTE) enoxaparin prophylaxis dosing remains elusive. Weight-based (WB) dosing safely increases anti-factor Xa levels without the need for routine monitoring but it is unclear if it leads to lower VTE risk. We hypothesized that WB dosing would decrease VTE risk compared with standard fixed dosing (SFD). METHODS: Patients from the prospective, observational CLOTT-1 registry receiving prophylactic enoxaparin (n=5539) were categorized as WB (0.45-0.55 mg/kg two times per day) or SFD (30 mg two times per day, 40 mg once a day). Multivariate logistic regression was used to generate a predicted probability of VTE for WB and SFD patients. RESULTS: Of 4360 patients analyzed, 1065 (24.4%) were WB and 3295 (75.6%) were SFD. WB patients were younger, female, more severely injured, and underwent major operation or major venous repair at a higher rate than individuals in the SFD group. Obesity was more common among the SFD group. Unadjusted VTE rates were comparable (WB 3.1% vs. SFD 3.9%; p=0.221). Early prophylaxis was associated with lower VTE rate (1.4% vs. 5.0%; p=0.001) and deep vein thrombosis (0.9% vs. 4.4%; p

Background: Non-life-threatening cases treated by emergency services have been increasing in recent years, especially in older people. In a region in Germany with approximately 600,000 inhabitants, the role of a specially trained community paramedic (Gemeindenotfallsanitäter, G-NFS) was introduced in 2019. The G-NFS is dispatched to low-acuity requests, attends the assignment alone and is allowed to treat patients at home. Aim: The aim of this study was to analyse the assignments attended by the G-NFS relating to the suspected diagnoses, with a focus on older people (≥ 65 years) according to their care setting. Methods: In this descriptive, retrospective study, we analysed the anonymous assignment report forms 07/2023–12/2023 of cases where patients were aged ≥ 65 years. The suspected diagnoses (free text field) were categorised according to the International Classification of Primary Care 2nd Edition (ICPC-2) scheme. Furthermore, baseline characteristics, urgency of the assignment, provided measures, transport and further treatment were analysed, stratified by care setting. Results: Of the 1,643 included anonymous assignment report forms, 52.9% (n = 869) related to patients aged ≥ 65 years. In this population, the mean age was 80.7 years (SD 8.2), 49.6% were female and most were in long-term care, whether as home care recipients (34.8%) or as nursing home residents (26.9%). The most frequent diagnoses were categorised as urological (24.9%), general and unspecified (13.7%), circulatory (13.6%), digestive (12.8%), musculoskeletal (11.5%) and respiratory (10.3%). In 52.7% of the cases no transport was necessary, while 73.7% of urological cases did not need to be transported. Conclusion: The G-NFS was dispatched mainly to older people. Most of them were in long-term care and were not transported. The most common suspected diagnoses were categorised as urological, followed by general and unspecified, and circulatory, and differed by care setting. There is a strong need to strengthen outpatient healthcare structures for low-acuity health issues in older and immobile patients. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion An innovative New South Wales government funded statewide Cannabis Medicines Advisory Service (CMAS) operated between January 2018 and June 2022. The service provided comprehensive patient‐specific and evidence‐based information to support health professionals in prescribing and patient care decisions. This study aimed to describe real‐world data collected by CMAS.A sub‐set of de‐identified, patient‐specific enquiries collected between January 2021 and June 2022 (n = 123/567; 21.7%) were analyzed using R version 4.2.1. Diagnosis, indication, and comorbidities were coded using Medical Dictionary for Regulatory Activities (MedDRA) terminology.Most patient‐specific enquiries from medical practitioners were from general practitioners (n = 103/123; 83.7%). Female (n = 53/123; 43.1%) and male (n = 59/123; 48.0%) patients were similarly represented. Sex was not specified for 8.9% (n = 11/123) of patients. The mean age of patients was 52.1 years (range <10–90). The most common three diagnoses were osteoarthritis, anxiety, and chronic pain. Indications that were most frequently reported included chronic pain, anxiety, back pain, non‐neuropathic pain, and insomnia. Comedications were most commonly non‐opioid and opioid analgesics and antidepressants. Most practitioners were considering prescribing a cannabidiol (CBD) product for their patient. Cannabinoid composition selection guidance provided by CMAS was predominantly (delta‐9‐tetrahydrocannabinol) THC:CBD ~1:1, followed by CBD‐only products. CMAS was contacted by health professionals regarding the management of potential adverse events for five patients.The findings of this study shed light on the information medical practitioners were seeking to inform their clinical decision‐making about medical cannabis and can inform the development of clinical guidance resources. [ABSTRACT FROM AUTHOR]

Background: Recently, there has been a growing interest in combining causal inference with machine learning algorithms. Double machine learning model (DML), as an implementation of this combination, has received widespread attention for their expertise in estimating causal effects within high-dimensional complex data. However, the DML model is sensitive to the presence of outliers and heavy-tailed noise in the outcome variable. In this paper, we propose the robust double machine learning (RDML) model to achieve a robust estimation of causal effects when the distribution of the outcome is contaminated by outliers or exhibits symmetrically heavy-tailed characteristics. Results: In the modelling of RDML model, we employed median machine learning algorithms to achieve robust predictions for the treatment and outcome variables. Subsequently, we established a median regression model for the prediction residuals. These two steps ensure robust causal effect estimation. Simulation study show that the RDML model is comparable to the existing DML model when the data follow normal distribution, while the RDML model has obvious superiority when the data follow mixed normal distribution and t-distribution, which is manifested by having a smaller RMSE. Meanwhile, we also apply the RDML model to the deoxyribonucleic acid methylation dataset from the Alzheimer's disease (AD) neuroimaging initiative database with the aim of investigating the impact of Cerebrospinal Fluid Amyloid β 42 (CSF A β 42) on AD severity. Conclusion: These findings illustrate that the RDML model is capable of robustly estimating causal effect, even when the outcome distribution is affected by outliers or displays symmetrically heavy-tailed properties. [ABSTRACT FROM AUTHOR]

Background: The NOVA study (NCT01847274) compared niraparib with placebo as a maintenance treatment for patients with recurrent ovarian cancer (OC) but was not powered to detect an overall survival (OS) improvement. Objective: To compare OS in a real-world population of patients with BRCA wild-type (BRCA wt) recurrent OC who received second-line maintenance (2LM) niraparib monotherapy versus active surveillance (AS). Design: A retrospective study using a US-based nationwide deidentified electronic health record-derived database. Methods: Patients diagnosed with epithelial OC (January 1, 2011–May 31, 2021) who completed second-line (2L) therapy (January 1, 2017–March 2, 2022) and were BRCA wt were included. A NOVA study-like subpopulation included patients with an Eastern Cooperative Oncology Group performance status score of 0–1 and platinum-sensitive disease. Patients were assigned to 2LM niraparib or AS cohorts. Follow-up was measured from the index date (2L non-maintenance therapy end) until the first of study end (May 31, 2022), last clinical activity, or death. Median OS (mOS) and hazard ratios were estimated with an emulated trial methodology. Results: The overall population comprised 199 patients in the 2LM niraparib monotherapy cohort and 707 patients in the AS cohort; the NOVA study-like subpopulation included 123 patients in the 2LM niraparib monotherapy cohort and 143 in the AS cohort. Demographic and clinical characteristics were similar in both populations. Overall, adjusted mOS was 24.1 months for the 2LM niraparib monotherapy cohort versus 18.4 months for the AS cohort (hazard ratio, 0.8; 95% confidence interval [CI]: 0.7–0.9). In the NOVA study-like subpopulation, adjusted mOS was 28.1 months for the 2LM niraparib monotherapy cohort versus 21.5 months for the AS cohort (hazard ratio, 0.6; 95% CI: 0.5–0.9). Conclusion: These results provide important real-world OS data for patients with recurrent BRCA wt OC who received niraparib monotherapy compared with patients receiving AS. Plain language summary: Niraparib maintenance treatment versus monitoring for recurrent ovarian cancer without BRCA mutation This study examined the real-life survival of patients with ovarian cancer (OC) who received two lines of chemotherapy for OC, known as recurrent OC. We compared two groups: one patient group received a subsequent oral medication called niraparib (a type of maintenance therapy) to delay recurrence, whereas the other group was monitored by their physicians without receiving any medication (also known as active surveillance). This study analyzed health records from across the United States, focusing on patients who were diagnosed with OC between January 2011 and May 2021. Importantly, these patients completed their second line of therapy between January 2017 and March 2022 and had BRCA wild-type disease (meaning that they did not have a specific gene mutation known as BRCA). Patients then received maintenance therapy with niraparib or active surveillance. To assess how long patients lived, patient records were reviewed until the study ended in May 2022, or for patients who did not have data available through that date, until the date of their last visit or death. The study found a significant difference in how long the two groups of patients survived on average. Those patients who received the medication niraparib survived for 24.1 months, compared with 18.4 months for patients in the group that was monitored by their physicians. These results provide valuable insights into the real-life benefits of using niraparib to treat OC outside of a clinical trial. Importantly, these results support the positive outcomes seen in clinical trials, indicating that this medication is a promising option for patients with recurring OC. [ABSTRACT FROM AUTHOR]

Background: Assessing maternal health care utilisation is imperative for the health of both mother and her child. Maternal education is an important determinant in subsequent maternal health care usage, according to research. There is a dearth of research on the causal relationship between maternal education and maternal health services as well as examining the performance of different propensity score methods for estimating absolute effects. Therefore, this study aims to estimate the effect of maternal education on usage of maternal health services minimising the confounding effect and to compare different propensity score approaches to estimate absolute effects of maternal education on usage of maternal health services. Methods: We used data from a cross-sectional study conducted by icddr,b in Bangladesh. A total of 1300 recently delivered mothers were included in this study. We used different propensity score (PS) methods to estimate the causal effect of maternal education on receiving maternal health services, including PS matching, PS weighting, covariate adjustment using PS, as well as used modified log-Poisson regression with and without multiple covariates. Results: The study revealed highly imbalanced possible confounding factors for mother's educational level, which might lead to erroneous estimates. All methods indicated a significant effect of higher maternal education, whether measured as a continuous scale or a binary variable (secondary or higher vs. below secondary) on maternal health services, significantly increased the likelihood of receiving four or more ANC, delivered at facility, PNC within 42 days and receiving all maternal health services compared to the mothers with lower level of education. The PS weighting provided precise estimates with a low range of confidence interval. Conclusions: The results provided important insights on how well these techniques worked to reduce effect of confounding variables and achieve precise estimates. Propensity score weighting method performed better in terms of providing more precise estimates with a narrower range of confidence intervals, indicating that this method may be a reliable approach for estimating the causal effect of maternal education on maternal health service utilisation. However, careful consideration should be given to selecting the most appropriate method. [ABSTRACT FROM AUTHOR]

The article discusses the discontinuation of SGLT2 inhibitors (SGLT2i) in individuals with type 2 diabetes following hospitalization for heart failure. The study found that nearly 30% of SGLT2i users discontinued therapy within 90 days of discharge, with one in five remaining off treatment at 365 days. Factors such as age, hospitalization duration, number of prior hospitalizations, and chronic kidney disease were associated with higher discontinuation rates. The study highlights the importance of minimizing SGLT2i discontinuation to reduce mortality and readmission risk in individuals with type 2 diabetes after a heart failure hospitalization. [Extracted from the article]

Objective: To clarify the causal relationship between anxiety-depression and the progression and outcomes of vitiligo, providing a basis for enhancing psychological interventions in the treatment of vitiligo. Methods: A two-sample Mendelian randomization analysis was used to validate the causal relationship between anxiety, depression, and vitiligo. The Hospital Anxiety and Depression Scale (HADS) assessed the psychiatric condition of vitiligo patients. Fisher's chi-square tests and rank sum tests analyzed the differences in clinical characteristics among vitiligo patients with different HADS scores. Regression analysis assessed the correlation between anxiety-depression and disease progression and treatment outcomes. Results: Mendelian randomization analysis showed that depression significantly increases the risk of vitiligo (OR = 4.46, 95% CI: 1.16–17.18, p = 0.03). According to the HADS scores, clinical characteristics differed significantly among the groups (p < 0.05). Univariate regression analysis demonstrated that both HADS (B = –1.168, p < 0.001, 95% CI: −1.532 to −0.804) and VIDA (B = –2.157, p < 0.001, 95% CI: −3.464 to −0.887) were significantly negative associated factors for disease outcomes. However, HADS (B = –1.006, p < 0.001, 95% CI: −1.475 to −0.657) emerged as the only factor influencing therapeutic efficacy in multivariate regression analysis. A restricted cubic spline graph illustrates a U-shaped relationship between HADS and clinical efficacy, with the most significant impact on therapeutic efficacy occurring when HADS equals 15. Conclusion: Anxiety—depression exhibit a bidirectional positive causal relationship with vitiligo. Moderate to severe anxiety-depression significantly influences the clinical efficacy of vitiligo treatment. [ABSTRACT FROM AUTHOR]

Background: The latest guidelines discourage the use of long-acting beta2-agonists/inhaled corticosteroids (LABA/ICS) for chronic obstructive pulmonary disease (COPD). However, there is a lack of evidence regarding the optimal subsequent treatment after discontinuing LABA/ICS. Objectives: To compare the effectiveness and safety of switching from LABA/ICS to triple therapy (LABA/long-acting muscarinic antagonists (LAMA)/ICS) or to dual bronchodilators (LABA/LAMA) in COPD patients. Design: This was a new-user, active-comparator, and propensity score-matched cohort study analyzing the Taiwanese nationwide healthcare insurance claims. Methods: We recruited COPD patients switching from LABA/ICS to triple therapy or to dual bronchodilators from 2015 to 2019. The primary effectiveness outcome was the annual rate of exacerbations, and safety outcomes included severe pneumonia and all-cause mortality. Stratification by prior exacerbations was conducted. Results: After matching, each group comprised 1892 patients, 55% of whom experienced no exacerbations in the prior year. Treatment with LABA/LAMA/ICS versus LABA/LAMA showed comparable annual rate of moderate-to-severe exacerbations (incidence rate ratio, 1.04; 95% confidence interval (CI), 0.91–1.19). However, switching to LABA/LAMA/ICS was associated with increased risks of severe pneumonia (hazard ratio (HR), 1.65; 95% CI, 1.30–2.09) and all-cause death (HR, 1.39; 95% CI, 1.09–1.78). In patients with⩾2 prior exacerbations, LABA/LAMA/ICS versus LABA/LAMA was related to a 21% reduced rate of exacerbations but with a twofold increased pneumonia risk and a 49% elevated risk of all-cause mortality. Conclusion: Switching from LABA/ICS to triple therapy versus dual bronchodilators in COPD patients was associated with similar rates of annual exacerbations but was related to elevated risks of severe pneumonia and all-cause mortality. Among frequent exacerbators, triple therapy was associated with lower rates of exacerbation but was accompanied by increased risks of pneumonia and mortality compared to LABA/LAMA. Careful consideration of the examined safety events is necessary when switching from LABA/ICS to triple therapy in COPD management. [ABSTRACT FROM AUTHOR]

The difference in restricted mean survival time has been increasingly used as an alternative measure to the hazard ratio in survival analysis. Although some statistical methods have been developed for estimating the difference in restricted mean survival time adjusted for measured confounders in observational studies, the impact of unmeasured confounding on the estimate has rarely been assessed. We develop a novel sensitivity analysis for the estimate of the difference in restricted mean survival time with respect to unmeasured confounding. After formulating the sensitivity analysis problem as an optimization problem, we explain how to obtain the sensitivity range of the difference in restricted mean survival time efficiently and assess its uncertainty using the percentile bootstrap confidence interval. Analytic results are provided for some important survival settings. Simulation studies show that the proposed methods perform well in various settings. We illustrate the proposed sensitivity analysis method by analyzing data from the German Breast Cancer Study Group study. [ABSTRACT FROM AUTHOR]

Introduction: Daratumumab, lenalidomide, and dexamethasone (DRd) and bortezomib, lenalidomide, and dexamethasone (VRd) are the only preferred treatment regimens for patients with transplant‐ineligible (TIE) newly diagnosed multiple myeloma (NDMM). As there are no randomized head‐to‐head studies of DRd versus VRd, this analysis aimed to compare real‐world time‐to‐next‐treatment (TTNT) or death in this population. Methods: Patients with NDMM who received front‐line (FL) DRd or VRd were identified from the Acentrus database (January 1, 2018 to May 31, 2023). Those with a record of a stem cell transplant or aged < 65 years were excluded to limit analysis to the TIE population. Inverse probability of treatment weighting was used to balance baseline patient characteristics. A doubly robust Cox proportional hazards model was used to compare TTNT or death between cohorts. Results: A total of 149 and 494 patients who initiated DRd and VRd, respectively, were identified. After weighting (weighted NDRd = 302, weighted NVRd = 341), cohorts had similar baseline characteristics. Of these, 98 (32.4%) DRd and 175 (51.2%) VRd patients either received a subsequent line of therapy or died, with a median TTNT or death of 37.8 months in the DRd cohort and 18.7 months in the VRd cohort (hazard ratio: 0.58, 95% confidence interval: 0.35, 0.81; p < 0.001). Conclusion: Treatment of TIE NDMM patients with DRd led to a significantly longer TTNT or death compared to VRd, evidenced by a 42% risk reduction, supporting the effectiveness of DRd over VRd as FL treatment in this patient population. [ABSTRACT FROM AUTHOR]

In recent times, the world has witnessed unprecedented challenges, with the COVID-19 pandemic being a major disruptor to various aspects of daily life. This article delves into the profound impact of pandemics on primary care, specifically focussing on changes in antidepressant prescriptions and mental health referrals before, during, and after lockdowns in England, UK. In this retrospective study, we used anonymised individual-level electronic health record data from general practitioner (GP) practices in the North of England, UK. We applied a negative binomial-logit hurdle model and a multinominal logit regression model to assess the impact on antidepressant prescriptions and GP referral types, respectively. The initiation of antidepressant prescriptions showed a notable decrease during and post lockdowns, with a minor uptick in ongoing antidepressant prescriptions during the lockdown periods. Over the course of lockdowns and beyond, there was a growing trend of patients being referred to social prescribing interventions. Notably, individuals from ethnic minorities were more inclined to receive fewer medical treatments and more social prescribing interventions. The increase in antidepressant prescriptions during the pandemic-related lockdowns was expected due to these challenging circumstances. Reduced referrals to secondary mental health services occurred as online counselling services were deemed inappropriate by some doctors, and patients were hesitant to seek face-to-face help. Notably, there was a rise in social prescribing referrals, emerging as a valuable resource for psychological support amid heightened mental health strain. Additionally, ethnic minority patients were less likely to receive medical treatments but more likely to be referred to social prescribing services. Despite the inevitable negative impacts of the COVID-19 pandemic, these findings highlight the active role of non-clinical support in a social model of health, addressing unmet needs and reducing barriers to mental health care for certain groups. [ABSTRACT FROM AUTHOR]

Aims: To investigate the independent contributions of glycated haemoglobin (HbA1c) reduction and weight loss to clinical outcomes in patients with type 2 diabetes (T2D) treated with antidiabetic drugs, including glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs). Materials and Methods: This observational, retrospective cohort study used deidentified electronic health record‐derived data from patients evaluated at the Cleveland Clinic (1 January 2000–31 December 2020). Cohort A included 8876 patients with newly diagnosed T2D treated with any of six antidiabetic drug classes. Cohort B included 4161 patients with T2D initiating GLP‐1RA treatment. The effects of body mass index (BMI) and HbA1c reduction, variability, and durability on clinical outcomes were investigated. Results: In Cohort A, each 1% BMI reduction was associated with 3%, 1%, and 4% reduced risk of heart failure (p = 0.017), hypertension (p = 0.006), and insulin initiation (p = 0.001), respectively. Each 1% (~11 mmol/mol) HbA1c reduction was associated with 4% and 29% reduced risk of hypertension (p = 0.041) and insulin initiation (p = 0.001), respectively. In Cohort B, each 1% BMI reduction was associated with 4% and 3% reduced risk of cardiovascular disease (p = 0.008) and insulin initiation (p = 0.002), respectively. Each 1% (~11 mmol/mol) HbA1c reduction was associated with 4% and 16% reduced risk of chronic kidney disease (p = 0.014) and insulin initiation (p = 1 × 10−4), respectively. Lower BMI variability and greater BMI durability were associated with decreased risk of clinical outcomes in both cohorts. Conclusions: Antidiabetic medication‐associated, and specifically GLP‐1RA‐associated, weight loss and HbA1c reductions independently reduce real‐world clinical outcome risk. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the utilization and costs of non‐insulin glucose‐lowering drugs (GLDs) in Australia from 2013 to 2023. Materials and Methods: We conducted a retrospective analysis of the Australian Pharmaceutical Benefits Scheme (PBS) administrative dataset of 118 727 494 GLD prescriptions. The main outcome measures were the annual number of GLD prescriptions dispensed, accounting for type 2 diabetes mellitus (T2DM) prevalence and healthcare system costs, adjusted for inflation. Results: Utilization of GLDs doubled from 6.4 million prescriptions in 2013 to 15.6 million in 2023. The average annual percent increase in utilization was 8.1%, compared to the average annual increase in prevalence of T2DM of 1.8%. The biggest change was in sodium‐glucose cotransporter‐2 (SGLT2) inhibitors, for which there was an average annual increase in utilization of 59.4% (95% confidence interval [CI] 51.7%, 68.2%; p < 0.05) from 2014 (first full year of PBS listing), followed by glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs), which showed an increase of 31.4% (95% CI 28.5%, 33.8%; p < 0.05) annually (2013 to 2023). Dipeptidyl peptidase‐4 inhibitor utilization tripled, with an average annual increase of 10.9% (95% CI 8.1%, 13.8%; p < 0.05), but this plateaued from 2020. Metformin utilization increased by 4.7% (95% CI 2.0%, 6.9%; p < 0.05) annually. In contrast, sulphonylurea, glitazone and acarbose utilization declined. Total GLD costs increased threefold over the same period. Despite only accounting for 11.7% of utilization, GLP‐1RAs contributed to 35% of the costs. Conclusion: Utilization of GLDs doubled, and associated costs tripled over the past 11 years, with no sign of either utilization or costs plateauing, predominantly due to increased GLP‐1RA and SGLT2 inhibitor prescribing. [ABSTRACT FROM AUTHOR]

Aim: To establish trust in real‐world evidence (RWE) derived from CareLink Personal (CP), Medtronic's data management system for MiniMed system users, we show that this database and its analyses strictly adhere to the principles of RWE. Methods: The methodology is applicable to all MiniMed iterations. We described every step from raw data to predefined outcomes. In addition, we showed CP's fitness‐for‐research by the below metrics (using last year's MiniMed 780G system data as a case study): representative population, relevant endpoints, appropriate granularity, high data completeness, high data representativity and consistency in results. Results: The process from raw data to outcomes has been validated, and metrics/logics adhere to established definitions. Over 95% of users have a CP account; with 96% providing consent, this allows the use of >91% of the census population. There is no rationale for an over‐representation of a specific phenotype among users not included. CP includes >50 endpoints, including 'International Consensus on Time in Range' based metrics. Data are recorded at 5‐min intervals (maximum 288 per day), and on average there were 263 data points per person per day. Ninety‐nine per cent of uploads were automated. For the last year, only 1 in 6 users had a data gap >1 day, and 1 in 50 had a gap >1 week. The time in range from in‐silico studies was similar to that of real‐world studies from different geographies and with ever growing populations. Conclusion: RWE from CP adheres to the principles of RWE and can serve as robust evidence on the performance and safety of MiniMed systems. [ABSTRACT FROM AUTHOR]

Aim: To assess the prevalence of individual obesity‐related complications (ORCs) and multimorbidity (≥ 1, ≥ 2 and ≥ 3 ORCs), and multimorbidity‐associated healthcare costs, over 10 years. Methods: This retrospective open cohort study used Discover, a UK database of linked primary and secondary electronic health records. Adults were stratified by body mass index (BMI; overweight: 25‐< 30 kg/m2; obesity class I: 30‐< 35 kg/m2; obesity class II: 35‐< 40 kg/m2; obesity class III: ≥ 40 kg/m2). Outcomes by year since baseline were assessed for serial cross sections across the study period (1 January 2004 to 31 December 2019; the index date was the date of first eligible BMI measurement). Results: Across 1 410 146 individuals (overweight: 1 008 101; obesity class I: 278 782; obesity class II: 80 621; obesity class III: 42 642), ORC prevalence was higher in successive BMI groups, and increases over time were generally greater for obesity relative to overweight. In those with ORC multimorbidity, both higher BMI and the presence of more ORCs were associated with higher annual per‐person healthcare costs. Costs increased over time in those individuals with obesity and one or more ORC, as well as in those with obesity and two or more ORCs. Conclusions: Higher BMI was associated with higher baseline ORC prevalence and a greater increase in ORC prevalence over time, and with higher healthcare costs in those with multimorbidity. To reduce the burden of overweight and obesity on patients and healthcare systems, the presence, number and type of ORCs should be considered in developing effective, targeted prevention and management care pathways. [ABSTRACT FROM AUTHOR]

Aims: To estimate healthcare resource utilization (HCRU) and healthcare costs by body mass index (BMI) in a UK cohort and to explore how this varied by defined BMI strata. Materials and Methods: This retrospective open cohort study used Discover, a linked primary and secondary electronic health records database covering 2.7 million individuals. Adults were stratified by BMI as: overweight (25–<30 kg/m2); obesity class I (30–<35 kg/m2); obesity class II (35–<40 kg/m2); or obesity class III (≥40 kg/m2). Cost data, comprising primary care, secondary care (inpatient admissions, outpatient appointments and emergency room visits) and prescriptions, were reported for 2015–2019. Results: Overall, 1 008 101 individuals were overweight, 278 782 had obesity class I; 80 621 had obesity class II, and 42 642 had obesity class III. Healthcare costs and HCRU events per person per year increased over time (2015: £851–£1321 and 10.6–13.4 events; 2019: £1143–£1871 and 11.4–14.9 events), and were higher for each successive BMI group. Groups with chronic kidney disease or cardiovascular disease incurred particularly high costs. In 270 493 individuals with obesity in 2019, more than 72% of total healthcare costs were incurred by the highest cost quintile, which had a higher mean age and more obesity‐related complications (ORCs) than lower cost quintiles. Conclusions: The economic impact of obesity could be alleviated by weight management support based on unmet need, to limit the effects of BMI progression and ORC development. [ABSTRACT FROM AUTHOR]

Background: Nonsuicidal self-injury (NSSI) is highly prevalent in adolescents and young adults worldwide. It is linked to a broad variety of mental disorders and an increased suicide risk. Despite its high prevalence, research on the underlying mechanisms and on potential risk and resilience factors for maintaining or quitting NSSI remains scarce. This manuscript presents an overview of the "Self-injury: Treatment-Assessment-Recovery" (STAR) collaboration, which aimed to address these gaps. Methods: We investigated the natural course of NSSI as well as its social, psychological, and neurobiological predictors (observational study; OS). OS data collection occurred at four timepoints (baseline [T0], 4 [post, T1], 12 [follow-up (FU), T2], and 18 [FU, T3] months after baseline) for the NSSI group, which was compared to a healthy control (HC) group at T0 only. Online self-report was used at all timepoints, while semi-structured interviews (face-to-face (f2f)) were conducted at T0 and T3. At T0 only, we conducted ecological momentary assessment and neurobiological investigations. Here, we present the general methodology and sample characteristics of the completed OS including the f2f subprojects, while other subprojects are not within the scope of this paper. Sample description: The OS sample consists of 343 participants at T0 (180 NSSI, 163 HC). Mean age in the NSSI group (T0) was 18.1 years (SD = 2.09, range: 15–25), gender-related data is available for 166: 156 = female, 7 = male, 3 = transgender, 10 = not disclosed). In the HC group, mean age (T0) was 19.1 years (SD = 2.35, range: 15–25) (142 = female, 21 = male). At T1, 128 (71.11%) of the NSSI participants completed the questionnaires, at T2 125 (69.44%) and at T3 104 (57.78%). In the fMRI subproject, 126 adolescents participated (NSSI = 66, HC = 60, 100% female; mean age (T0): NSSI = 18.10 years, SD = 2.21; HC = 19.08, SD = 2.36). Conclusion: Understanding predictors is of utmost importance for adequate diagnosis and intervention for NSSI. Our OS applied a multimodal investigation of social, psychological, and neurobiological parameters and is the largest sample of adolescents with NSSI to date including follow-up assessments. As health care providers require specific knowledge to develop new treatments, we believe that our in-depth assessments can potentially enhance care for youths engaging in NSSI. [ABSTRACT FROM AUTHOR]

Aims Materials and Methods Results Conclusions This study aimed to explore the effect of discontinuation of long‐term spironolactone treatment on markers of kidney function in individuals with type 2 diabetes (T2D) at high risk of kidney disease enrolled in the Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria (PRIORITY) study.An observational study following the nested randomised part of the PRIORITY study was conducted. A total of 115 individuals with T2D and normoalbuminuria but high risk for progression based on urinary proteomics, randomised to daily spironolactone (n = 50) or placebo (n = 65) for a median of 2.5 years, were re‐examined approximately 6 weeks after the final visit in the PRIORITY study. Primary endpoint was relative change in geometric mean of urinary albumin‐creatinine ratio (UACR) between the final visit in PRIORITY (baseline) and follow‐up. Secondary endpoints were change in estimated glomerular filtration rate (eGFR), systolic blood pressure (SBP) and serum potassium.No change in UACR was observed in neither the spironolactone (geometric mean change: 17%; 95% CI −12, 55; p = 0.28) nor the placebo (5%; 95% CI −13, 26; p = 0.63) group at follow‐up. No difference in UACR between the groups was observed at follow‐up (relative difference in geometric mean: 11%, 95% CI −26, 67; p = 0.60). For eGFR and SBP, an increase after discontinuation of spironolactone was observed, as well as for SBP after placebo discontinuation. Potassium levels were lower after discontinuation of spironolactone, but higher after placebo discontinuation (all p < 0.05).UACR did not change after discontinuation of long‐term treatment with spironolactone. However, an increase in eGFR was observed supporting a haemodynamic effect of spironolactone in the kidneys. [ABSTRACT FROM AUTHOR]

Background: Frailty often requires intensive care, and the admission outcomes of frail patients are often poor. However, owing to the lack of reliable diagnostic indicators, quickly identifying frailty is challenging. The present study aimed to explore the associations of the platelet/high-density lipoprotein cholesterol ratio (PHR; a novel inflammatory indicator) with frailty and all-cause mortality. Methods: The present study analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. Frailty was assessed on the basis of the 49-item Frailty Index. The associations of the PHR with frailty and long-term survival prognosis were explored through weighted logistic regression, weighted restricted cubic spline (RCS), and weighted Cox regression, with adjustments for demographic factors, lifestyle, blood lipids, medication history, and complications. In addition, subgroup and interaction analyses were conducted. Finally, several sensitivity analyses were performed. Results: A total of 15,615 adult participants were included, with 7,928 women (53.63%) and an average age of 60.76 years. After fully adjusting for confounding variables, the prevalence of frailty in the highest PHR quartile group of was significantly greater than that in the lowest quartile group (OR: 1.23, 95% CI: 1.04–1.47; P = 0.02). The RCS showed that the inflection point was 166.7. Before and after the inflection point, the PHR was negatively associated (OR: 0.88, 95% CI: 0.80–0.97, P = 0.01) and positively associated (OR: 1.10, 95% CI: 1.02–1.19, P = 0.01) with frailty, respectively. Subgroup analysis suggested that the association between PHR and frailty was stronger in women than in men. A total of 5,544 frail participants were included in the survival analysis. The RCS revealed that the PHR was associated with the all-cause mortality risk of frail participants in a U-shaped manner, with an inflection point of 240.4. Before and after the inflection point, the PHR decreased (HR: 0.89, 95% CI: 0.81–0.97, P = 0.01) and the all-cause mortality risk increased (HR: 1.08, 95% CI: 1.02–1.14, P = 0.01), respectively. Conclusion: The present study suggests that there is a J-shaped association between PHR and frailty in the adult population of the United States and that the association between the PHR and frailty is stronger in women. In addition, the PHR has a U-shaped relationship with the all-cause mortality risk of frail patients. [ABSTRACT FROM AUTHOR]

Background: Malnutrition is a complication of chronic kidney disease (CKD). Whether malnutrition, assessed via the geriatric nutritional risk index (GNRI), is associated with the incidence and risk of CKD in older individuals remains unclear. Methods: Data from the National Health and Nutrition Examination Survey and the UK Biobank database were used. Older participants over 60 years old with available data for GNRI assessment and CKD diagnosis were enrolled. Logistic regression models and Cox regression models were used to assess associations between the geriatric nutritional risk index and the risk of and mortality associated with CKD. Results: This study enrolled 13,162 participants from the NHANES and 66,326 participants from the UK Biobank. We identified 6,135 and 16,662 CKD patients in the NHANES and UK Biobank, respectively, with the majority being male (74% in the NHANES and 52% in the UK Biobank). The average age of CKD patients was 72.3 (SD 7.2) years in the NHANES and 64.9 (SD 2.9) years in the UK Biobank. The median follow-up times of older CKD patients were 81 months and 162 months in the NHANES and UK Biobank, respectively. According to the cross-sectional analysis, individuals with a lower GNRI had an increased likelihood of having CKD, with odds ratios of 1.38 (95% CI: 1.05–1.80, P = 0.020) in the NHANES and 2.35 (95% CI: 1.89–2.92, P < 0.001) in the UK Biobank. According to our analysis of the risk of incident CKD in the UK Biobank, a lower GNRI was associated with a greater incidence of CKD (HR: 1.11, 95% CI: 1.04–1.18; P = 0.002). According to the analysis of the risk of mortality, a lower GNRI was associated with an increased risk of death among older CKD patients (NHANES: HR: 1.69, 95% CI: 1.13–2.53, P = 0.011; UK Biobank: HR: 2.28, 95% CI: 1.94–2.69, P < 0.001). Conclusion: Malnutrition assessed by the GNRI was significantly and independently associated with the incidence of CKD. Moreover, CKD patients with malnutrition also have a high risk of mortality. [ABSTRACT FROM AUTHOR]

Background: Musculoskeletal alterations causing reduced range of motion of the ankle joint are common in children with cerebral palsy (CP). Objective measurements of passive joint resistance and three-dimensional skeletal muscle volume and muscle architecture can lead to a comprehensive understanding of which factors influence joint range of motion. Research question: To investigate the relation between the passive dorsiflexion of the ankle joint, biomechanical contributing factors to the passive joint resistance, and muscular architectural properties of the triceps surae muscle in children with CP. Methods: In this cross-sectional observational study, 14 children with spastic CP (bilateral: 5, unilateral: 9, Gross Motor Function Classification System (GMFCS) level I:11, II:3) naïve to intramuscular tone reducing treatment, and 14 TD children were included. The passive dorsiflexion of the ankle was measured with a goniometer. Passive joint resistance and related parameters were estimated based on a biomechanical model and measurements using a motorized device, the Neuroflexor. Three-dimensional muscle architecture was quantified with diffusion tensor magnetic resonance imaging (DT-MRI). Results: In the CP group, the median [min, max] passive dorsiflexion was decreased in the most affected leg (MAL) compared to the less affected leg (LAL) (2.5° [-25°, 20°] vs. 12.5° [5°, 30°], p = 0.001). The stiffness coefficient (Nm/rad) in the MAL was significantly higher in children with CP compared to TD children (7.10 [3.39, 62.00] vs. 2.82 [1.24, 10.46], p = 0.015). Muscle architecture properties did not differ between CP and TD, except for pennation angle in the medial gastrocnemius (MG) of the MAL (CP 17.64° (2.29) vs. TD 21.46° (3.20), p = 0.017). The stiffness coefficient, in the MAL, correlated negatively to passive dorsiflexion (rs=-0.638) and pennation angle in medial gastrocnemius (rs=-0.964), and the non-linear coefficient (Non-linear 1) correlated negatively to the fascicle length of the medial gastrocnemius (rs=-0.857). Conclusion: This study shows that stiffness of the plantarflexors is related to decreased passive dorsiflexion of the ankle and muscle structure of the MG in high-functioning children with spastic CP. Assessments of how dynamic components as well as microscopic muscle alterations contribute to joint stiffness in the plantarflexors in individuals with CP are warranted. Trial registration: Retrospectively registered in ClinicalTrials.gov, NCT05447299. Observational study. Study start: 2019-01-15, register date: 2022-07-01. [ABSTRACT FROM AUTHOR]

Background: Adverse pregnancy outcomes have reached epidemic proportions in recent years with serious health ramifications, especially for diverse cancers risk. Therefore, we carried out an umbrella review to systematically evaluate the validity and strength of the data and the extent of potential biases of the established association between adverse pregnancy outcomes and cancers risk in both mother and offspring. Methods: PubMed, Embase, and Web of Science databases were searched from inception until 18 January 2024. Meta-analyses of observational studies investigating the relationship between adverse pregnancy outcomes and multiple cancers risk in both mother and offspring were included. Evidence certainty was assessed using Grading of Recommendations, Assessment, Development, and Evaluation. The protocol for this umbrella review was prospectively registered in PROSPERO (CRD42023470544). Results: The search identified 129 meta-analyses of observational studies and 42 types of cancer. Moderate certainty of evidence, exhibiting statistical significance, has been observed linking per kilogram increase in birth weight to a heightened risk of breast cancer (OR = 1.07, 95% CI = 1.02–1.12), prostate cancer (OR = 1.02, 95% CI = 1.00–1.05), leukemia (OR = 1.18, 95% CI = 1.13–1.23), and acute lymphoblastic leukemia in offspring (OR = 1.18, 95% CI = 1.12–1.23); rubella infection during pregnancy to an increased risk of leukemia in offspring (OR = 2.79, 95% CI = 1.16–6.71); and a linear dose–response association between an increase in the proportion of optimal birth weight and an elevated risk of acute lymphoblastic leukemia in offspring (OR = 1.16, 95% CI = 1.09–1.24), respectively. Conclusions: Although some adverse pregnancy outcomes have clinically promising associations with risk of several cancers in both mother and offspring, it is essential to conduct additional research to solidify the evidence, evaluate causality, and ascertain clinical utility. [ABSTRACT FROM AUTHOR]

Background: The procedures used to assess the methodological quality and risk of bias (RoB) of systematic reviews of observational dental studies have not been investigated. The purpose of this research was to examine the way that authors of systematic reviews of epidemiological observational studies published in dentistry conducted the methodological assessment of those primary studies. In the present article, we aimed to assess the characteristics and the level of reporting of tools used to assess the methodologies of these reviews. Methods: We searched Scopus and the Web of Science from their inceptions to June 2023 for systematic reviews with meta-analyses of observational studies published in dentistry. Document selection and data extraction were performed in duplicate and independently by two authors. In a random sample of 10% of the systematic reviews, there was an agreement of more than 80% between the reviewers; data selection and extraction were conducted in the remaining 90% of the sample by one author. Data on the article and systematic review characteristics were extracted and recorded for descriptive reporting. Results: The search in the two databases resulted in the inclusion of 3,214 potential documents. After the elimination of duplicates and the application of the eligibility criteria, a total of 399 systematic reviews were identified and included. A total of 368 systematic reviews reported a methodological tool, of which 102 used the Newcastle–Ottawa scale. Additionally, 76 systematic reviews stated the use of a modified methodological tool. Information about the approach of assessing the methodological quality or RoB of primary studies but reporting no tool or tool name occurred in 25 reviews. Conclusions: The majority of authors of systematic reviews of epidemiological observational studies published in dentistry reported the tools used to assess the methodological quality or RoB of the included primary studies. Modifying existing tools to meet the individual characteristics of various studies should be considered. [ABSTRACT FROM AUTHOR]

Background: While traditional medicine (TM) is employed by a significant portion of the global population for managing health issues, clinical guidelines and state recommendations often overlook this practice. The aim of this study was to describe the frequency of use of TM to control 3 metabolic risk factors (MRF): hypertension, hypercholesterolemia, and hyperglycaemia; and the sociodemographic, economic, and clinical characteristics associated with the use of TM. Methods: Cross-sectional descriptive study that analyses data obtained from a representative population survey in 2 health districts, one urban in the south of Quito and another in a forested rural area with diverse ethnic groups in Esmeraldas, Ecuador. We include 602 individuals with at least one MRF. We calculated the proportion of people reporting the regular use of TM (herbal or traditional remedy) to control their MRF and we assessed potential associations with sociodemographic, economic, and clinical characteristics with a multivariable logistic regression model. Results: In two very different sociocultural contexts in Ecuador we found that use of TM to control MRF was frequent (39.4% in Esmeraldas, 31.1% in Quito), frequently in combination with CM. There is a notable percentage of people, 33.9% in Esmeraldas and 39.0% in Quito, who did not take any treatment for their MRF, and the remainder used CM alone. In both settings, an individual's education lever was significantly associated with TM use. Whereas in Quito individuals with higher education more frequently treated their MRF with TM (aOR 2.04, 95% CI 1.03–3.90), in the rural, hard-to-reach context of Esmeraldas, it was more frequent among people with no formal schooling (aOR: 3.76; 95%CI 1.59–8.88), as well as those of younger age (aOR by year: 0.97; 95% CI 0.95–0.99) and afro ethnicity (aOR: 2.13; 95%CI 1.02–4.45). Conclusion: Traditional medicine is used by a significant proportion of the population in Ecuador, highlighting the need for a more accessible and intercultural healthcare approach. The health system should ensure access to the necessary information and resources for the management of their metabolic risk factors. [ABSTRACT FROM AUTHOR]

Objective: To clarify the causal relationship between anxiety-depression and the progression and outcomes of vitiligo, providing a basis for enhancing psychological interventions in the treatment of vitiligo. Methods: A two-sample Mendelian randomization analysis was used to validate the causal relationship between anxiety, depression, and vitiligo. The Hospital Anxiety and Depression Scale (HADS) assessed the psychiatric condition of vitiligo patients. Fisher's chi-square tests and rank sum tests analyzed the differences in clinical characteristics among vitiligo patients with different HADS scores. Regression analysis assessed the correlation between anxiety-depression and disease progression and treatment outcomes. Results: Mendelian randomization analysis showed that depression significantly increases the risk of vitiligo (OR = 4.46, 95% CI: 1.16-17.18, p = 0.03). According to the HADS scores, clinical characteristics differed significantly among the groups (p < 0.05). Univariate regression analysis demonstrated that both HADS (B = -1.168, p < 0.001, 95% CI: -1.532 to -0.804) and VIDA (B = -2.157, p < 0.001, 95% CI: -3.464 to -0.887) were significantly negative associated factors for disease outcomes. However, HADS (B = -1.006, p < 0.001, 95% CI: -1.475 to -0.657) emerged as the only factor influencing therapeutic efficacy in multivariate regression analysis. A restricted cubic spline graph illustrates a U-shaped relationship between HADS and clinical efficacy, with the most significant impact on therapeutic efficacy occurring when HADS equals 15. Conclusion: Anxiety--depression exhibit a bidirectional positive causal relationship with vitiligo. Moderate to severe anxiety-depression significantly influences the clinical efficacy of vitiligo treatment. [ABSTRACT FROM AUTHOR]

Background We aimed to evaluate the effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations in previously SARS-CoV-2–infected adults in the general population of Austria during the Delta wave and with extended follow-up. Methods In a nationwide retrospective cohort study, we calculated age-, sex-, and nursing home residency–adjusted Cox proportional hazard ratios (HRs) of coronavirus disease 2019 (COVID-19) deaths, SARS-CoV-2 infections, and non-COVID-19 deaths from 1 October to 31 December 2021, and secondarily with extended follow-up to 30 June 2022. Relative vaccine effectiveness (rVE) is rVE = (1 – HR) × 100. Results Among 494 646 previously infected adults, 169 543 had received 2 vaccine doses, 133 567 had received 1 dose, and 190 275 were unvaccinated at baseline. We recorded 17 COVID-19 deaths (6 vaccinated, 11 unvaccinated) and 8209 SARS-CoV-2 infections. Absolute risk of COVID-19 deaths was 0.003%. rVE estimates for COVID-19 deaths and reinfections exceeded 75% until the end of 2021 but decreased substantially with extended follow-up. The risk of non-COVID-19 death was lower in those vaccinated versus unvaccinated. Conclusions First and second SARS-CoV-2 vaccine doses appear effective in the short-term, but with diminishing effectiveness over time. The extremely low COVID-19 mortality, regardless of vaccination, indicates strong protection of previous infection against COVID-19 death. Lower non-COVID-19 mortality in the vaccinated population might suggest a healthy vaccinee bias. [ABSTRACT FROM AUTHOR]

Background/Objectives: Patients with Non-Alcoholic Fatty Liver Disease (NAFLD) are reported to have an increased risk of developing severe infections, leading to hospitalizations with sepsis. However, data regarding the impact of comorbid NAFLD on in-hospital outcomes of patients with sepsis is scarce. Methods: This nationwide retrospective observational study using discharge data from the National Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), and Agency for Healthcare Research and Quality included 21,057,911 adult patients who were admitted to hospitals in the United States between 2000 and 2019 with a primary discharge diagnosis of sepsis. These patients were categorized according to the presence or absence of comorbid NAFLD. The twenty-year trend of nationwide NAFLD prevalence among sepsis inpatients was elucidated. Multivariable logistic regression analysis was used to analyze NAFLD's impact on sepsis outcomes. Results: In the twenty-year study period, the prevalence of NALFD among sepsis inpatients trended up from 1.2% in 2000 to 4.2% in 2019. Similar trends were observed in regional analysis. While overall sepsis mortality decreased, comorbid NAFLD in sepsis patients was consistently associated with a higher adjusted in-hospital all-cause mortality rate (adjusted odds ratio (OR), 1.19; 95% confidence interval (CI), 1.07–1.32), higher odds of developing septic shock, and higher likelihood of development of multi–organ dysfunction. Conclusions: Comorbid NAFLD in the stage of NASH or cirrhosis is associated with higher in-hospital all-cause mortality and worse clinical outcomes in sepsis inpatients. Addressing this rising epidemic will be of paramount importance to improve sepsis in-hospital outcomes. [ABSTRACT FROM AUTHOR]

Background: Neck reflex points (NRPs) are 2 × 6 potentially tender areas of the neck, denominated NRP-C0 to NRP-C7. They are different from muscular trigger points and become tender in response to chronic trigeminal irritation. NRP examination has a high inter-rater reproducibility. We investigated the prevalence of NRPs in two populations to investigate their usefulness as a clinical test for trigeminal irritation. Methods: In total, 165 patients with chronic pain and 431 students were examined for NRP tenderness using a three-level pain scale: absent pain (PI = 0), mild tenderness (PI = 1), or marked tenderness (PI = 2). Results: In patients, we found more tender NRPs than in the student group (p < 0.001), and on the left side, more tender NRPs were found in NRP-C0–C4. Left and right NRPs appeared independently (kappa 0.1–0.4), except for NRP-C7 (kappa 0.55). Females had more tender NRPs (p < 0.001). Tenderness was independent of age, BMI, and pre-existing diseases. Conclusions: NRP tenderness occurs more frequently in patients than in students, independent from potential covariates. Our results, together with previous findings, support the use of NRP examination as a clinical test for chronic silent inflammation of the trigeminal region. These data provide a base for further studies investigating correlations of NRPs with clinical findings. [ABSTRACT FROM AUTHOR]

Background Worldwide, atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in adults and poses a significant burden to patients, physicians, and healthcare systems. We developed a quality of care score based on the Atrial Fibrillation Better Care pathway recommended by the European Society of Cardiology and the European Heart Rhythm Association guidelines. This is a 14-point score that we have termed the MAGIC score(Management of Atrial Fibrillation in Integrated Care and General Practice). Objective The objective of this pilot study was to develop and test a quality of care score for patients with permanent AF in general practice. Methods An observational cross-sectional pilot study was undertaken. Proportionate sampling was used across 11 practices from the Ireland East practice-based research network. The GPs completed a report form on each patient by undertaking a retrospective chart review. Eleven practices participated with a total of 1855 patients with AF. We received data on 153 patients. Results The main findings were that no patient met all 14 guideline based recommendations. The mean MAGIC score was 11.3. Points were most commonly deducted because the creatinine clearance and HAS-BLED score were not recorded, and the patient was not on the correct dose of oral anti-coagulation. Conclusion This study demonstrates the feasibility of using a quality of care score to measure the quality of AF management in general practice. This scoring system, which is based on internationally recognized quality of care markers, highlights key areas that can be targeted with quality improvement intervention. [ABSTRACT FROM AUTHOR]

Background: Abnormal lipid metabolism is linked to intervertebral disc degeneration (IVDD), sciatica, and low back pain (LBP), but it remains unclear whether targeted interventions can prevent these issues. This study investigated the causal effects of lipid-lowering drug use on IVDD, sciatica, and LBP development. Methods: Single-nucleotide polymorphisms (SNPs) linked to total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), and non-high-density-lipoprotein cholesterol (non-HDL-C) were obtained from the Global Lipids Genetics Consortium's genome-wide association study (GWAS). Genes near HMGCR, PCSK9, and NPC1L1 were selected to represent therapeutic inhibition targets. Using Mendelian randomization (MR) focusing on these drug targets, we identified causal effects of PCSK9, HMGCR, and NPC1L1 on the risk of developing IVDD, sciatica, and LBP, with coronary heart disease risk serving as a positive control. Using summary data from Mendelian randomization (SMR) analysis, we evaluated potential therapeutic targets for IVDD, sciatica, and LBP through protein quantitative trait loci (pQTL). The genetic associations with IVDD, sciatica, LBP, and coronary heart disease were derived from FinnGen (discovery) and UK Biobank (replication). Additionally, a cross-sectional observational study was performed using data from the National Health and Nutrition Examination Survey (NHANES) to further investigate the connection between LBP and statin use, with a sample size of 4343 participants. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to assess the outcomes. Results: The NHANES-based cross-sectional study indicated that non-statin use was associated with an increased risk of developing LBP (OR = 1.29, 95% CI [1.04, 1.59], P = 0.019). Moreover, Inverse-variance weighting (IVW) analysis revealed that NPC1L1-mediated reductions in TC, LDL-C, and non-HDL-C concentrations were associated with a decreased risk of developing IVDD (P = 9.956E-03; P = 3.516E-02; P = 1.253E-04). Similarly, PCSK9-mediated reductions in LDL-C and TC concentrations were linked to a lower risk of developing sciatica (P = 3.825E-02; P = 2.709E-02). Sensitivity analysis confirmed the stability and reliability of the MR results. MST1 (macrophage stimulating 1) levels was inversely associated with IVDD, sciatica, and LBP risks. Conclusion: The results of cross-sectional study suggested that non-use of statins was positively correlated with LBP. The results of Mendelian randomization study suggest that NPC1L1 could lower the risk of developing IVDD by reducing TC, LDL-C, and non-HDL-C levels. Additionally, PCSK9 may reduce the risk of developing sciatica by lowering LDL-C and TC levels. In contrast, HMGCR appears to have no significant effect on IVDD, sciatica, or LBP development. Nonetheless, further research is needed to verify these preliminary results. MST1 warrants further exploration as a potential therapeutic target. It is necessary to do further research to validate these findings. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions Hospitalizations for adverse drug reactions (ADR‐HA) have increased over the last decade, but the impact of ADR‐HA has rarely been evaluated. The aim of this study was to estimate the economic burden of ADR‐HA in France.A partial economic evaluation from the viewpoint of French public health insurance was performed, based on a previous pharmacovigilance study (IATROSTAT) performed in 2018 in public hospital medical units. The cost included direct medical costs, collected retrospectively, from the French hospital discharge database. The economic burden was estimated by calculating the total cost per ADR‐HA patient (cost of hospital stays, additional daily cost of specific stays, such as in a resuscitation, intensive care or continuous surveillance unit, drug products and medical devices in addition to Healthcare Resource Group‐based tariffs, and specific outpatient consultations and other clinical and technical medical procedures, over 3 months as from the first day of ADR‐HA). The robustness of the results was assessed using a one‐way deterministic sensitivity analysis of cost factors applying tariffs from 2023 instead of 2018.According to the 2018 tariffs (vs. 2023), the mean total cost per patient with ADR‐HA was estimated at €5208 ± €3719 (vs. €5974 ± €4232) ranging from €514 to €23 355 (vs. €618 to €27 380). The total cost for 196 patients with ADR‐HA admitted to a sample of French public hospitals was estimated at €1 020 549 (vs. €1 170 960). It could be estimated at €1.3 billion at the national level.In addition to the increase in the number of expensive drugs, the ageing population and polypharmacy, the economic impact of serious ADR‐HA weighs heavily on healthcare spending. [ABSTRACT FROM AUTHOR]

Purpose: We investigated whether a 52-gene signature was associated with transplant-free survival and other clinically meaningful outcomes in patients with idiopathic pulmonary fibrosis (IPF) in the IPF-PRO Registry, which enrolled patients who were and were not taking antifibrotic therapy. Methods: The 52-gene risk signature was implemented to classify patients as being at "high risk" or "low risk" of disease progression and mortality. Transplant-free survival and other outcomes were compared between patients with a low-risk versus high-risk signature. Results: The 52-gene signature classified 159 patients as at low risk and 86 as at high risk; in these groups, respectively, 56.6% and 51.2% used antifibrotic therapy at enrollment. Among those taking antifibrotic therapy, patients with a low-risk versus high-risk signature were at decreased risk of death, a composite of lung transplant or death, and a composite of decline in DLco % predicted > 15%, lung transplant, or death. Similar results were observed in the overall cohort. Conclusions: These data suggest that the 52-gene signature can be used in patients with IPF treated with antifibrotic therapy to distinguish patients at higher risk of disease progression and mortality. [ABSTRACT FROM AUTHOR]

Aim: The relative contributions of insulin secretory defects and possible additional contribution of insulin resistance for the development of cystic fibrosis (CF)‐related diabetes (CFRD) are poorly understood. We aimed to (a) determine which indices of insulin resistance predict progression to CFRD, and (b) to model the relative contributions of insulin secretory function and insulin resistance to predict the risk of CFRD. Materials and Methods: Three hundred and three individuals living with CF underwent a 2‐h oral glucose tolerance test with blood sampling every 30 min at 12–24‐month intervals until they developed CFRD or until the end of follow‐up (up to 15 years). Indices of insulin resistance (e.g. Stumvoll) and insulin secretion were calculated from oral glucose tolerance test glucose and insulin measurements. CFRD‐free survival was assessed by survival analysis. Results: Estimated insulin resistance showed associations with glucose homeostasis and risk of progression to CFRD. The CFRD‐free survival was significantly different between quartiles of insulin resistance (p < 0.0001). When patients were subdivided according to both insulin resistance and insulin secretion (insulinogenic index), CFRD‐free survival was significantly lower in those with combined lowest insulin secretion and highest insulin resistance (Stumvoll) indices (hazard ratio: 11.2; p < 0.0001). There was no significant difference when the same analysis was performed for the nine other indices. Conclusions: Insulin resistance is correlated with glucose homeostasis and the risk of progression to CFRD. Patients combining low insulin secretion and high insulin resistance had the greatest odds of developing CFRD over a 15‐year period. [ABSTRACT FROM AUTHOR]

Aim: To examine the associations of tea consumption (both frequency and type) with (1) prediabetes and diabetes and (2) urinary glucose and sodium excretion in Chinese community‐dwelling adults. Materials and Methods: In 1923 participants (457 with diabetes, 720 with prediabetes, and 746 with normoglycaemia), the frequency (occasional, frequent, daily, or nil) and type (green, black, dark, or other) of tea consumption were assessed using a standardized questionnaire. Morning spot urinary glucose and urine glucose‐to‐creatinine ratios (UGCRs) were assessed as markers of urinary glucose excretion. Tanaka's equation was used to estimate 24‐h urinary sodium excretion. Logistic and multivariate linear regression analyses were performed. Results: Compared with non‐tea drinkers, the corresponding multivariable‐adjusted odds ratios (ORs) for prediabetes and diabetes were 0.63 (95% confidence interval [CI] 0.48, 0.83) and 0.58 (95% CI 0.41, 0.82) in participants drinking tea daily. However, only drinking dark tea was associated with reduced ORs for prediabetes (0.49, 95% CI 0.36, 0.66) and diabetes (0.41, 95% CI 0.28, 0.62). Dark tea consumption was associated with increased morning spot urinary glucose (0.22 mmol/L, 95% CI 0.11, 0.34 mmol/L), UGCR (0.15 mmol/mmol, 95% CI 0.05, 0.25 mmol/L) and estimated 24‐h urinary sodium (7.78 mEq/day, 95% CI 2.27, 13.28 mEq/day). Conclusions: Regular tea consumption, especially dark tea, is associated with a reduced risk of dysglycaemia and increased urinary glucose and sodium excretion in Chinese community‐dwelling adults. [ABSTRACT FROM AUTHOR]

Aim: To investigate the clinical significance of body weight changes on kidney outcomes among individuals with diabetes using sodium–glucose cotransporter‐2 (SGLT2) inhibitors. Materials and Methods: This is a retrospective cohort study using a nationwide epidemiological database, and we conducted an analysis involving 11 569 individuals with diabetes who were newly prescribed SGLT2 inhibitors. The main outcome was the rate of decline in estimated glomerular filtration rate (eGFR), determined through a linear mixed‐effects model with an unstructured covariance structure. Results: The median age of the patients was 52 (Q1–Q3: 47–58) years, and the median fasting plasma glucose and glycated haemoglobin (HbA1c) levels were 144 (Q1–Q3: 124–175) mg/dL and 7.4 (Q1–Q3: 6.8–8.3)%, respectively. The median estimated eGFR was 77.7 (Q1–Q3: 67.2–89.1) mL/min/1.73 m2. The median follow‐up period was 1.7 (Q1–Q3: 1.0–2.6) years. Participants were stratified into three groups based on the body mass index change rate tertiles between baseline and 1 year after (tertile 1: <−4.55%, tertile 2: −4.55% to −1.43%, tertile 3: >−1.43%). The annual change in eGFR was −0.78 (−0.94 to −0.63) mL/min/1.73 m2 in tertile 1, −0.95 (−1.09 to −0.81) mL/min/1.73 m2 in tertile 2, and −1.65 mL/min/1.73 m2 (−1.84 to −1.47) in tertile 3 (pinteraction < 0.001). A variety of sensitivity analyses confirmed the relationship between the 1‐year body mass index decrease and favourable kidney outcomes after SGLT2 inhibitor administration. Conclusions: Our analysis of a nationwide epidemiological cohort revealed that kidney outcomes following the initiation of SGLT2 inhibitors would be more favourable, with greater body weight loss observed after the initiation of SGLT2 inhibitors. [ABSTRACT FROM AUTHOR]

Aim: To evaluate associations between social disadvantage and insulin pump use among adults with type 1 diabetes (T1D) in the context of a universal publicly funded insulin pump programme in Ontario, Canada, and to ascertain whether social disparities in insulin pump programme enrolment have decreased over time. Methods: Population‐based cross‐sectional studies were conducted using administrative healthcare data in Ontario, Canada. First, among adults aged older than 18 years diagnosed with T1D before 31 March 2021, logistic regression was used to assess the association between neighbourhood social disadvantage (Ontario marginalization index quintiles) and insulin pump use. Second, among all paediatric and adult applicants to the insulin pump programme from 1 September 2006 to 31 March 2022, ordinal logistic regression was used to evaluate associations between year of insulin pump initiation and social disadvantage. Results: Among 27 453 adults with T1D, 60% used insulin pumps. Greater social disadvantage was associated with lower odds of insulin pump use (adjusted odds ratio [OR] 0.44 [95% confidence interval {CI} 0.39‐0.48] for greatest vs. lowest social disadvantage quintile). Among 21 002 paediatric and adult applicants to the insulin pump programme, social disparities in pump use decreased in the first 3 years of the programme, plateaued until 2020, then increased from 2020 to 2022, with no change in the odds of being in a higher social deprivation quintile for 2022 relative to 2007 (OR 1.09 [95% CI 0.83‐1.44]). Conclusions: Despite a universal pump programme for individuals with T1D, disparities by social disadvantage persist. Residual financial and non‐financial barriers must be addressed to promote equitable insulin pump uptake. [ABSTRACT FROM AUTHOR]

Aim: To investigate the associations of the Dietary Approaches to Stop Hypertension (DASH) score with subcutaneous (SAT) and visceral (VAT) adipose tissue volume and hepatic lipid content (HLC) in people with diabetes and to examine whether changes in the DASH diet were associated with changes in these outcomes. Methods: In total, 335 participants with recent‐onset type 1 diabetes (T1D) and type 2 diabetes (T2D) from the German Diabetes Study were included in the cross‐sectional analysis, and 111 participants in the analysis of changes during the 5‐year follow‐up. Associations between the DASH score and VAT, SAT and HLC and their changes were investigated using multivariable linear regression models by diabetes type. The proportion mediated by changes in potential mediators was determined using mediation analysis. Results: A higher baseline DASH score was associated with lower HLC, especially in people with T2D (per 5 points: −1.5% [−2.7%; −0.3%]). Over 5 years, a 5‐point increase in the DASH score was associated with decreased VAT in people with T2D (−514 [−800; −228] cm3). Similar, but imprecise, associations were observed for VAT changes in people with T1D (−403 [−861; 55] cm3) and for HLC in people with T2D (−1.3% [−2.8%; 0.3%]). Body mass index and waist circumference changes explained 8%‐48% of the associations between DASH and VAT changes in both groups. In people with T2D, adipose tissue insulin resistance index (Adipo‐IR) changes explained 47% of the association between DASH and HLC changes. Conclusions: A shift to a DASH‐like diet was associated with favourable VAT and HLC changes, which were partly explained by changes in anthropometric measures and Adipo‐IR. [ABSTRACT FROM AUTHOR]

Aim: Non‐randomized studies on bariatric surgery have reported large reductions in mortality within 6‐12 months after surgery compared with non‐surgical patients. It is unclear whether these findings are the result of bias. Study Design and Setting: We searched PubMed to identify all non‐randomized studies investigating the effect of bariatric surgery on all‐cause mortality compared with non‐surgical patients. We assessed these studies for potential confounding and time‐related biases. We conducted bias analyses to quantify the effect of these biases. Results: We identified 21 cohort studies that met our inclusion criteria. Among those, 11 were affected by immortal time bias resulting from the misclassification or exclusion of relevant follow‐up time. Five studies were subject to potential confounding bias because of a lack of adjustment for body mass index (BMI). All studies used an inadequate comparator group that lacked indications for bariatric surgery. Bias analyses to correct for potential confounding from BMI shifted the effect estimates towards the null [reported hazard ratio (HR): 0.78 vs. bias‐adjusted HR: 0.92]. Bias analyses to correct for the presence of immortal time also shifted the effect estimates towards the null (adjustment for 2‐year wait time: reported HR: 0.57 vs. bias‐adjusted HR: 0.81). Conclusion: Several important sources of bias were identified in non‐randomized studies of the effectiveness of bariatric surgery versus non‐surgical comparators on mortality. Future studies should ensure that confounding by BMI is accounted for, considering the choice of the comparator group, and that the design or analysis avoids immortal time bias from the misclassification or exclusion. [ABSTRACT FROM AUTHOR]

Background: The comparative effectiveness of selective serotonin reuptake inhibitors (SSRIs) has been subjected to relatively little research. However, a recent study based on target trial emulation suggested that sertraline may be more effective than escitalopram. Aims: To investigate whether sertraline, citalopram, and escitalopram differ in their effectiveness—assessed via the risk of psychiatric hospital admission and suicide following treatment initiation. The choice to focus on sertraline, citalopram, and escitalopram was made to limit confounding by indication, as the Danish depression treatment guideline from 2007 specifically listed these three SSRIs as first choice. Method: We conducted a target trial emulation based on data from Danish registers. We identified all individuals that initiated treatment for depression with sertraline, citalopram, or escitalopram in the period from January 1, 2007, to March 1, 2019. These individuals were followed until psychiatric hospital admission or suicide (separate analyses), death, 1 year after treatment initiation or end of data. Cox proportional hazards regression adjusted for relevant baseline covariates was performed to emulate randomized treatment allocation, comparing the rate of psychiatric hospital admission and suicide for individuals treated with sertraline (used as reference), citalopram or escitalopram, respectively. For escitalopram, we conducted a sensitivity analysis excluding data from the period during which the drug was sold under patent, as the price of the drug during that time likely entailed a different prescription pattern, increasing the risk of ("patent‐related") confounding by indication. Results: We identified 56,865, 118,145, and 31,083 individuals initiating treatment with sertraline, citalopram, and escitalopram, respectively. Using sertraline as reference, the adjusted hazard rate ratio (aHRR) for psychiatric admission was 0.98 (95% CI = 0.91–1.05) for citalopram and 1.21 (95% CI = 1.10–1.32) for escitalopram. Notably, in the sensitivity analysis only including patients initiating treatment after the escitalopram patent had expired, the increased risk of psychiatric hospital admission associated with escitalopram treatment was no longer present (aHRR = 0.98, 95% CI = 0.82–1.18). The results of the analyses of suicide were inconclusive, due to few outcome events. Conclusions: Sertraline, citalopram, and escitalopram do not seem to have differential effectiveness in the treatment of depression. Taking potential patent‐related, time varying, confounding by indication (via severity) into account is critical for pharmacoepidemiological studies, including those employing target trial emulation. [ABSTRACT FROM AUTHOR]

To evaluate the association of dry eye disease (DED) subtypes (aqueous deficient dry eye, ADDE and evaporative dry eye, EDE) and the presence of rheumatoid arthritis (RA) in patients. 260 volunteer DED participants were recruited for an observational cross-sectional study based on the Tear Film Ocular Society Dry Eye Workshop II criteria, which included tear film osmolarity, fluorescence break-up time, and ocular surface damage assessment. Participants were recruited using QR linked to designated mobile forms to obtain symptomatology status, demographics, and RA diagnosis by their medical doctor. Tear meniscus and lipid layer were also evaluated to differentiate between ADDE, EDE, or mixed dry eye in addition to the DED diagnostic criteria. Participants with mixed dry eye were excluded from the analysis to avoid bias. After initial recruitment, 149 eligible participants with an ADDE or EDE diagnosis were included in the final analysis, where 12,1% have an RA diagnosis. The ADDE group had a higher likelihood of having RA (OR = 4.69, 95 %CI = 1.46–15.01) than the EDE group. Additionally, the number of participants with RA in the ADDE group was statistically higher than those in the EDE group (all p = 0.006). Furthermore, a correlation was obtained between RA and a diagnosis of ADDE (p = 0.005). There was a significant association between ADDE and the presence of RA in patients and the association was more likely compared to those with EDE. This finding underscores the need for specific diagnostic and management strategies for RA patients presenting with DED. [ABSTRACT FROM AUTHOR]

Background: Despite programmatic protocolised care and structured support, considerable variation is observed in completeness of registration and achieving targets of cardiovascular risk management (CVRM) between individual GPs in the Netherlands. Aim: To determine whether completeness of registration and achieved targets of cardiovascular risk factors improves with practice visitation. Design & setting: Observational study utilising the care group's database (2016-2019), comparing changes in registration and achieved targets in non-visited practices and visited practices. Method: We compared completeness scores of registration and scores of targets achieved before visitation and 1 year after visitation. Data were analysed on patient level and GP level. Separate analyses were performed among GPs who were ranked in the lower 25% of score distributions. Results: We observed no clinically relevant improvements in completeness of registration and targets achieved in 2017, 2018, and 2019 that could be attributed to visitations in the previous year, both on individual patient level and on aggregated level per general practice. In practices ranked in the lower 25% of the distribution, improvements over time were clinically relevant and larger than the overall changes. Yet, these findings were irrespective of the number of practice visitations. Conclusion: Practice visitations in our setting did not seem to lead to improvements in practice performance, nor in completeness of registration of risk factors or in reaching predefined target goals for cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Pharmacists' job performance is crucial for improving pharmacy services. The purpose of this study was to evaluate the association of emotional intelligence with the job performance of pharmacists in Saudi Arabia. Using social media platforms, we disseminated an online questionnaire to pharmacists licensed to practice in Saudi Arabia between June and July 2022. The questionnaire was filled out by 352 pharmacists. The majority of the participants were women (60.5%) and working as community pharmacists (55.7%). On self-reported emotional intelligence and job performance scales, the respondents scored an average of 5.5 ± 0.9 (out of 7) and 4.0 ± 0.6 (out of 5), respectively. Multiple linear regression analyses revealed that emotional intelligence had a significant relationship with job performance (β = 0.43, p < 0.001). In conclusion, the findings indicated that emotional intelligence may influence the job performance of pharmacists in Saudi Arabia. As the primary objective of every organization is to accomplish the best possible performance, prioritizing emotional intelligence is important. Further research is needed to identify the impact of emotional intelligence on work performance, which could potentially enhance clinical outcomes for patients. [ABSTRACT FROM AUTHOR]

Background: It remains unknown whether composite-dietary-antioxidant-index (CDAI) is associated with the risk of sarcopenia. This study investigated the association of CDAI with sarcopenia risk among general US adults. Methods: A total of 10,093 participants were enrolled in the National Health and Nutrition Examination Surveys (NHANES) from 6 survey cycles (2003-2004, 2005-2006, 2011-2012, 2013-2014, 2015-2016 and 2017-2018). Multivariate logistic regression was carried out to examine the relationship between CDAI and the risk of sarcopenia. Restricted cubic spline (RCS) curves were employed to analyze nonlinear relationships. Results: In a multi-variable logistic regression model adjusting for demographics, lifestyle, economic status and other dietary factors, higher CDAI score was related to a lower risk of sarcopenia among US adults. Compared the highest quartile of CDAI score with the lowest, the OR and 95%CI were 0.49 (0.31-0.75). Furthermore, the RCS demonstrated a linear dose-response relationship between CDAI and sarcopenia (Pnon-linearity=0.92). These results remained consistent across subgroups stratified by age, sex, physical activity, drinking status, body mass index (BMI), smoking habits, energy intake, and Healthy Eating Index (HEI) score. In addition, the favorable associations of CDAI were primarily attributed to Vitamin E intake. Conclusion: A higher CDAI score was associated with a lower risk of sarcopenia. According to these results, a greater adherence to CDAI may benefit sarcopenia prevention in adults. [ABSTRACT FROM AUTHOR]

Rationale: Observational studies report a significant protective effect of antifibrotics on mortality among patients with idiopathic pulmonary fibrosis (IPF). Many of these studies, however, were subject to immortal time bias because of the mishandling of delayed antifibrotic initiation. Objectives: To evaluate the antifibrotic effect on mortality among patients with IPF using appropriate statistical methods that avoid immortal time bias. Methods: Using a large administrative database, we identified 10,289 patients with IPF, of whom 2,300 used antifibrotics. Treating delayed antifibrotic initiation as a time-dependent variable, three statistical methods were used to control baseline characteristics and avoid immortal time bias. Stratified analysis was performed for patients who initiated antifibrotics early and those who initiated treatment late. For comparison, methods that mishandle immortal time bias were performed. A simulation study was conducted to demonstrate the performance of these models in a wide range of scenarios. Results: All three statistical methods yielded nonsignificant results for the antifibrotic effect on mortality, with the stratified analysis for patients with early antifibrotic initiation suggesting evidence for reduced mortality risk (for all patients, hazard ratio, 0.89; 95% confidence interval, 0.79–1.01; P = 0.08; for patients who were 65 years or older, hazard ratio, 0.85; 95% confidence interval, 0.73–0.98; P = 0.03). Methods that mishandle immortal time bias demonstrated significantly lower mortality risk for antifibrotic users. Bias of these methods was evident in the simulation study, where appropriate methods performed well with little to no bias. Conclusions: Findings in this study did not confirm an association between antifibrotics and mortality, with a stratified analysis showing support for a potential treatment effect with early treatment initiation. [ABSTRACT FROM AUTHOR]

Objectives: The metabolic syndrome in patients with schizophrenia has consistently been a challenge for clinicians. Previous studies indicate that individuals with schizophrenia are highly prone to developing type 2 diabetes mellitus (T2DM). In recent years, a continuous stream of new observational studies has been reported, emphasizing the pressing need for clinicians to gain a more precise understanding of the association between schizophrenia and T2DM. The objective of this meta-analysis is to integrate new observational studies and further explore the potential link between schizophrenia and the risk of T2DM. Methods: We conducted a comprehensive search of PubMed, Cochrane Library, Embase, and Web of Science using medical subject headings (MeSH) and relevant keywords. The risk of bias in cohort studies and case-control studies was assessed using the Newcastle-Ottawa Scale (NOS), while cross-sectional studies were evaluated using the Agency for Healthcare Research and Quality scale (AHRQ), scoring was based on the content of the original studies. A fixedeffects model was employed if P > 0.1 and I2 ≤ 50%, indicating low heterogeneity. Conversely, a random-effects model was utilized if I2 > 50%, indicating substantial heterogeneity. Publication bias was assessed using funnel plots and Egger's test. Statistical analyses were carried out using Stata statistical software version 14.0. Results: This meta-analysis comprised 32 observational studies, involving a total of 2,007,168 patients with schizophrenia and 35,883,980 without schizophrenia, published from 2004 to 2023. The pooled analysis revealed a significant association between a history of schizophrenia and an increased risk of T2DM (Odds Ratio [OR] = 2.15; 95% Confidence Interval [CI]: 1.83--2.52; I2 = 98.9%, P < 0.001). Stratified by gender, females with schizophrenia (OR = 2.12; 95% CI: 1.70- 2.64; I2 = 90.7%, P < 0.001) had a significantly higher risk of T2DM than males (OR = 1.68; 95% CI: 1.39-2.04; I2 = 91.3%, P < 0.001). Regarding WHO regions, EURO (OR = 2.73; 95% CI: 2.23-3.35; I2 = 97.5%, P < 0.001) exhibited a significantly higher risk of T2DM compared to WPRO (OR = 1.72; 95% CI: 1.32-2.23; I2 = 95.2%, P < 0.001) and AMRO (OR = 1.82; 95% CI: 1.40-2.37; I2 = 99.1%, P < 0.001). In terms of follow-up years, the >20 years subgroup (OR = 3.17; 95% CI: 1.24- 8.11; I2 = 99.4%, P < 0.001) showed a significantly higher risk of T2DM than the 10-20 years group (OR = 2.26; 95% CI: 1.76-2.90; I2 = 98.6%, P < 0.001) and <10 years group (OR = 1.68; 95% CI: 1.30-2.19; I2 = 95.4%, P < 0.001). Conclusions: This meta-analysis indicates a strong association between schizophrenia and an elevated risk of developing diabetes, suggesting that schizophrenia may function as an independent risk factor for T2DM. [ABSTRACT FROM AUTHOR]

Introduction: Metabolic dysfunction-associated steatohepatitis (MASH) is increasingly becoming a prevalent cause of hepatocellular carcinoma (HCC). Our study examines the burden of MASH-related HCC globally, regionally, and nationally, along with associated risk factors from 1990 to 2019, considering variables such as age, sex, and socioeconomic status. Objective: We aimed to report the global, regional, and national burden of liver cancer due to MASH and its attributable risk factors between 1990 and 2019, by age, sex, and sociodemographic index (SDI). Methods: Utilizing the Global Burden of Disease 2019 project, we analyzed data on prevalence, mortality, and disability-adjusted life years (DALYs) for liver cancer attributable to MASH across 204 countries. We provided counts and rates per 100,000 population, including 95% uncertainty intervals. Results: In 2019, there were 46.8 thousand cases of MASH-related HCC, leading to 34.7 thousand deaths, and 795.8 thousand DALYs globally. While the prevalence increased by 19.8% since 1990, the death and DALY rates decreased by 5.3% and 15.1%, respectively. The highest prevalence was in High-income Asia Pacific, with the greatest increases observed in Australasia, Central Asia, and High-income North America. Southern Sub-Saharan Africa reported the highest death rate, while the lowest rates were in parts of Latin America, Central Sub-Saharan Africa, and Eastern Europe. DALY rates were the highest in Southern Sub-Saharan Africa and the lowest in Tropical Latin America. Discussion: The burden of MASH-related HCC is expected to rise slightly over the next decade. This disease, which is not associated with the SDI, remains a major public health problem. In addition, the escalating rates of obesity, demographic shifts, and an aging population could position MASH as a leading factor in liver cancer cases, surpassing viral hepatitis. It is imperative, therefore, that the forthcoming years see the implementation of strategic interventions aimed at the early detection and prevention of liver cancer associated with MASH. [ABSTRACT FROM AUTHOR]