Prevalence Of Disease Research Articles

Safety of fingolimod in patients with relapsing remitting multiple sclerosis: A descriptive analysis of data from the EudraVigilance database

The most prevalent disease course of Multiple Sclerosis (MS) is relapsing remitting multiple sclerosis (RRMS). Fingolimod (Gilenya®) was the first oral disease-modifying therapy to RRMS. Patients affected by MS require long-term treatment, making the ongoing evaluation of the safety profile of fingolimod imperative. The aim of this study was to analyze the post-marketing pharmacovigilance data of fingolimod in Europe.Data of 12-year period (1 January 2011–19 June 2023) were obtained from EudraVigilance, and a descriptive analysis using drug-reaction pairs was performed.A total of 22,957 reports were collected. The most reported adverse events (AEs) were related to nervous system disorders SOC (multiple sclerosis relapse n = 2271; 3.51%, headache n = 921; 1.42%, central nervous system lesion n = 893; 1,38%, dizziness 769; 1,19%, hypoaesthesia 487; 0.75% and multiple sclerosis 449; 0.69%), followed by investigations (lymphocyte count decreased n = 1648; 2.55%, white blood cell count decreased n = 833; 1.29%), blood and lymphatic system disorder (lymphopenia n = 1146; 1.77%), and general disorders and administration site condition (fatigue n = 1106; 1.71%, gait disturbance 564; 0.87%). A percentage of 23.00% of serious adverse events (SAEs), among the most reported were multiple sclerosis relapse (n = 2271; 15.27%), macular oedema (n = 793; 5.33%), bradycardia (n = 678; 4.56%), leukopenia (n = 533; 3.58%), and multiple sclerosis (n = 449; 3.02%).Most of AEs were non-serious, some SAEs related to cardiac, ophthalmic and infectious disorders emerged: their prevalence, along with the alignment of reported AEs with existing literature, supports the overall safety of fingolimod. Considering the rare and long-term ADRs that may arise in patients chronically treated for MS, continuous pharmacovigilance remains essential.

Clinical and molecular characterization of steatotic liver disease in the setting of immune-mediated inflammatory diseases

Background and aimsGrowing evidence suggest an increased prevalence of metabolic associated steatotic liver disease (MASLD) in the context of immune-mediated inflammatory diseases (IMIDs). We aimed to characterize clinically and mechanistically a prospective cohort of steatotic liver disease (SLD) in IMID patients compared to controls. MethodsCross-sectional, case‒control study including a subset of IMID patients. Controls from the general population were age-, sex-, type 2 diabetes-, and BMI-matched at a 1:2 ratio. SLD was established using controlled attenuation parameter. Liver biopsies were obtained when significant liver fibrosis was suspected. Total RNA was extracted from freshly frozen cases and analyzed by RNA-seq. Differential gene expression was performed with ‘limma-voom’. Gene set enrichment analysis was performed using the fgsea R package with a preranked “limma t-statistic” gene list. Results1456 IMID patients and 2945 controls were included. Advanced-SLD (LSM ≥9.7 kPa) (13.46% vs. 3.79%; p<0.001) and advanced-MASLD (12.8% vs. 2.8%; p<0.001) prevalence were significantly higher among IMID patients than controls. In multivariate analysis, concomitant IMID was an independent and the strongest predictor of advanced-SLD (Adjusted OR 3.318 [2.225-4.947]; p < 0.001). Transcriptomic data was obtained in 109 patients and showed 87 significant genes differentially expressed between IMID-MASLD and control-MASLD. IMID-MASLD cases displayed an enriched expression of genes implicated in pro-tumoral activities or the control of the cell cycle concomitant with a negative expression of genes related to metabolism. ConclusionsThe prevalence of advanced SLD and MASLD is disproportionately elevated in IMID cohorts. Our findings suggest that IMIDs may catalyse a distinct MASLD pathway, divergent from classical metabolic routes, highlighting the need for tailored clinical management strategies. Impact and implicationsThe prevalence of advanced fibrosis SLD is increased in patients with immune-mediated inflammatory diseases, independent of classic metabolic risk factors or high-risk alcohol consumption. The transcriptomic analysis reveals a unique gene expression signature associated with cellular activities that can be compatible with a liver condition leading to an accelerated and aggressive form of SLD. Our findings underscore the importance of heightened screening for advanced liver disease risk across various medical disciplines overseeing IMID patients.

Distribution of catheterisation laboratories in Indonesia 2017–2022: a nationwide survey

BackgroundGeographical terrains of Indonesia pose a major hindrance to transportation. The difficulty of transportation affects the provision of acute time-dependent therapy such as percutaneous coronary intervention (PCI). Also, Indonesia’s aging population would have a significant impact on the prevalence of acute coronary syndrome in the next decade. Therefore, the analysis and enhancement of cardiovascular care are crucial. The catheterisation laboratory performs PCI procedures. In the current study, we mapped the number and distribution of catheterisation laboratories in Indonesia. MethodsA direct survey was used to collect data related to catheterisation laboratory locations in July 2022. The population data was sourced from the Ministry of Home Affairs. The recent growth of catheterisation laboratories was examined and evaluated based on geographical areas. The main instruments for comparing regions and changes throughout time are the ratio of catheterisation laboratories per 100,000 population and the Gini index (a measure of economic and healthcare inequality. Gini index ranges from 0 to 1, with greater values indicating more significant levels of inequality). Regression analysis was carried out to see how the number of catheterisation laboratories was affected by health demand (prevalence) and economic capacity (Gross Domestic Regional Product [GDRP] per Capita). FindingsThe number of catheterisation laboratories in Indonesia significantly increased from 181 to 310 during 2017-2022, with 44 of the 119 new labs built in an area that did not have one. Java has the most catheterisation laboratories (208, 67%). The catheterisation laboratory ratio in the provinces of Indonesia ranges from 0·0 in West Papua and Maluku to 4·46 in Jakarta; the median is 1·09. (IQR 0·71–1·18). The distribution remains a problem, as shown by the high catheterisation laboratory Gini index (0·48). Regression shows that distribution of catheterisation laboratories was significantly affected by GDRP and the prevalence of heart disease. InterpretationThe number of catheterisation laboratories in Indonesia has increased significantly recently, however, maldistribution remains a concern. To improve Indonesia's cardiovascular emergency services, future development of catheterisation laboratories must be better planned considering the facility's accessibility and density. FundingIndonesia Endowment Fund for Education – Lembaga Pengelola Dana Pendidikan (LPDP)

A pilot trial of CRESCENT in a large academic healthcare system: A CaReEcoSystem primary Care Embedded demeNtia Treatment

ObjectiveThe prevalence of Alzheimer's Disease (AD) and related dementias is escalating, with substantial societal and economic impact. Existing dementia care is often inadequate due to underdiagnosis, delayed diagnosis, and insufficient resources, especially for caregivers. Behavioral symptoms of dementia further complicate care, contributing to negative outcomes. Collaborative care programs show promise, yet resource-intensive models can be challenging to scale. This study aimed to assess the feasibility of CRESCENT (CaReEcoSystem primary Care Embedded dementia Treatment), an adaptation of the CareEcosystem intervention, providing dementia care training to nurse care managers in a primary care setting. DesignEmbedded pilot cluster randomized controlled study. ParticipantsThe thirty nurse care managers enrolled in the trial had 393 patients with an ICD-10 diagnosis code consistent with dementia on their panels, 206 patients corresponding to the 15 intervention nurses and 187 patients corresponding to the 15 control nurses. MeasurementsPrimary outcome: Feasibility of capturing ED utilization using Medicare claims data and of implementing the intervention in a care management program. Secondary outcomes: ED use and change in caregiver distress (via survey) between baseline and 6-month follow-up using the Neuropsychiatric Inventory Questionnaire (NPI-Q) Distress scale. ResultsWe demonstrated the feasibility of collecting ED visit data through Medicare claims and of implementing the intervention in a busy care management program. In the 6-month follow-up, there were no changes in ED visits post-intervention. A non-significant 2.7-point greater reduction in caregiver distress among caregivers of PWD in the intervention cohort was observed. ConclusionA dementia care coordination program can be integrated into a care management program. Future trials will explore the effectiveness of CRESCENT in a fully powered clinical trial, aiming to address the rising dementia epidemic and improve dementia-informed care in healthcare systems.

Peripheral Arterial Disease in Nova Scotia: Increased Prevalence, Low Public Awareness and Poor Edinburg Claudication Questionnaire Sensitivity

BackgroundThe goal of this study was threefold: (1) assess the prevalence of peripheral arterial disease (PAD) in a Nova Scotian population, (2) evaluate the validity of the Edinburg Claudication Questionnaire (ECQ) in a Nova Scotian context, and (3) evaluate Nova Scotian public knowledge about PAD. MethodsParticipants were recruited from eight sites across Nova Scotia. In 2022, they were recruited at Heartland Tour® (HLT) sites—a provincial health promotion campaign. In 2023 they were recruited in communities coinciding with HLT sites (Public). Participants completed a demographics questionnaire, ECQ, and had an Ankle-Brachial Index (ABI) measurement. ABI of <0.9 was considered positive for presence of PAD. ResultsThere were 417 recruited participants, 263 from HLT, and 154 Public. 398 participants had ABI scores resulting in a PAD prevalence of 2.81% (249) in the HLT group, and 5.37% (149) in the public group. 394 participants had both ABI and ECQ scores, resulting with a found a sensitivity of 6.67% (CI 0.17-31.95%) and specificity of 97.63% (CI 95.54%-98.91%). 75% (311/417) of participants did not have prior knowledge of PAD. ConclusionPAD prevalence in both cohorts were higher than anticipated, with the Public cohort being over double the national average. This raises the question: should there be specific PAD targeted primary and/or secondary prevention strategies within the province? Our study demonstrated that a public-awareness campaign would be highly impactful due to low awareness within both cohorts, and that the ECQ was not an effective screening tool when used on the Nova Scotian population.

Accelerometer-Based Estimates of Physical Activity and Sedentary Time Among Samoan Adults.

The prevalence of obesity-related cardiometabolic disease in Samoa is among the highest globally. While physical activity is a modifiable risk factor for obesity-related disease, little is known about physical activity levels among adult Samoans. Using wrist-worn accelerometer-based devices, this study aimed to characterize physical activity among Samoan adults. Samoan adults (n = 385; 55% female, mean [SD] age 52 [10] y) wore Actigraph GT3X+ devices for 7 to 10days. General linear models were used to examine mean daily minutes of sedentary time, light physical activity, and moderate to vigorous physical activity by various participant characteristics. Time spent in moderate to vigorous physical activity did not differ statistically between men (88 [5]min; 95% confidence interval [CI], 80-97) and women (78 [4]min; 95% CI, 70-86; P = .08). Women, however, spent more time than men in light physical activity: 380 (7)minutes (95% CI, 367-393) versus 344 (7)minutes (95% CI, 329-358; P < .001). While there were no differences in physical activity by census region, education, or occupation among women, men in urban areas spent significantly less time in moderate to vigorous physical activity than those in peri-urban and rural areas (P = .015). Women with class II/III obesity spent more time in sedentary activities than those with healthy weight or overweight/class I obesity (P = .048). This study characterizes physical activity among Samoan adults and highlights variation by sex, urbanicity, and weight status. In providing initial device-measured estimates of physical activity in Samoa, this analysis establishes a baseline from which the success of future attempts to intervene on physical activity may be assessed.

Comparative effectiveness of positron emission tomography and single-photon emission computed tomography myocardial perfusion imaging for predicting risk in patients with cardiometabolic disease

BackgroundThe epidemiology of coronary artery disease (CAD) has shifted, with increasing prevalence of cardiometabolic disease and decreasing findings of obstructive CAD on myocardial perfusion imaging (MPI). Coronary microvascular dysfunction (CMD), defined as impaired myocardial flow reserve (MFR) by positron emission tomography (PET), has emerged as a key mediator of risk. We aimed to assess whether PET MFR provides additive value for risk stratification of cardiometabolic disease patients compared with single-photon emission computed tomography (SPECT) MPI. MethodsWe retrospectively followed patients referred for PET, exercise SPECT, or pharmacologic SPECT MPI with cardiometabolic disease (obesity, diabetes, or chronic kidney disease) and without known CAD. We compared rates and hazards of composite major adverse cardiovascular events (MACEs) (annualized cardiac mortality or acute myocardial infarction) among propensity-matched PET and SPECT patients using Poisson and Cox regression. Normal SPECT was defined as a total perfusion deficit (TPD) of <5%, reflecting the absence of obstructive CAD. Normal PET was defined as a TPD of <5% plus an MFR of ≥2.0. ResultsAmong 21,544 patients referred from 2006 to 2020, cardiometabolic disease was highly prevalent (PET: 2308 [67%], SPECT: 9984 [55%]) and higher among patients referred to PET (P < 0.001). Obstructive CAD findings (TPD > 5%) were uncommon (PET: 21% and SPECT: 11%). Conversely, impaired MFR on PET (<2.0) was common (62%). In a propensity-matched analysis over a median 6.4-year follow-up, normal PET identified low-risk (0.9%/year MACE) patients, and abnormal PET identified high-risk (4.2%/year MACE) patients with cardiometabolic disease; conversely, those with normal pharmacologic SPECT remained moderate-risk (1.6%/year, P < 0.001 compared to normal PET). ConclusionsCardiometabolic disease is common among patients referred for MPI and is associated with a heterogenous level of risk. Compared with pharmacologic SPECT, PET with MFR can detect nonobstructive CAD including CMD and can more accurately discriminate low-risk from higher-risk individuals.

Prevalence of Chronic Obstructive Pulmonary Disease and Its Associated Risk Factors in Yunnan Province, China: A Population Based Cross-Sectional Study.

Chronic obstructive pulmonary disease (COPD) is a significant disease impacting health and quality of life. Yunnan Province, a major tobacco producer, lacks comprehensive COPD studies. The purpose of this study is to describe the epidemic situation of COPD in Yunnan province and explore its influencing factors. This study is a cross-sectional research conducted in a representative sample of adults aged 20 and older from 13 prefectures and cities in Yunnan Province, China. COPD was diagnosed using post-bronchodilator pulmonary function tests. Demographics were analyzed with descriptive statistics. The influencing factors of COPD were examined by using the multivariate logistic regression models. Our study found that high-risk individuals for COPD accounted for 20.30% of the screened population aged 20 and above, with a COPD prevalence of 27.18% among this high-risk group. Male had a higher prevalence (33.01%) than did female (16.35%; p<0.001 for sex difference). Additionally, the proportion of severe and extremely severe COPD cases in Yunnan Province was higher than the national average and other provinces. After considering the potential confounding variables, male (OR=2.291, 95% CI: 1.584-3.313), age (OR=1.501, 95% CI: 1.338-1.685), underweight (OR=1.747, 95% CI: 1.225-2.491), previous smoking (OR=1.712, 95% CI: 1.182-2.478), passive smoking (OR=1.444, 95% CI: 1.159-1.800), and a history of respiratory system diseases in childhood (OR=2.010, 95% CI: 1.346-3.001) were significantly associated with an increased risk of COPD. Conversely, being overweight (OR=0.636, 95% CI: 0.489-0.828), and residing in high-altitude counties (OR=0.445, 95% CI: 0.263-0.754) were negatively correlated with the risk of COPD. There is significant prevalence of COPD (27.18%) among high-risk population aged 20 and above in Yunnan Province, China. Apart from male, smoking, BMI and other known risk factors for COPD. We found that high-altitude residence had a lower prevalence of COPD. There is no significant difference in COPD prevalence between Han and ethnic minority populations.

Excessive Daytime Napping Increases the Risk of Non-Alcoholic Fatty Liver Disease: A Meta-Analysis and a Mendelian Randomization Study.

Prior research based on observations has furnished evidence that supports a connection between daytime napping and the prevalence of non-alcoholic fatty liver disease (NAFLD). Nevertheless, the question of whether this correlation is indicative of a causal link has not been definitively answered. We used meta-analysis and Mendelian randomization (MR) to synthesize genetic and observational data. A two-sample MR analysis was conducted, leveraging 105 single-nucleotide polymorphisms (SNPs) known to be associated with daytime napping patterns. Additionally, summary-level data pertaining to NAFLD outcomes were acquired from the comprehensive UK Biobank study. Network meta-analyses were employed to investigate the relationship between excessive daytime napping and NAFLD, while subgroup was also performed. Significant associations were observed between daytime napping and NAFLD. The systematic review/meta-analysis uncovered a heightened risk of NAFLD development among individuals who engaged in daytime naps exceeding 30 minutes, when compared to those who did not nap(odds ratio [OR] = 1.32, 95% confidence interval [CI]: 1.05 to 1.66). Furthermore, MR analysis indicated that a genetic propensity towards longer daytime napping was significantly linked to an increased likelihood of NAFLD (OR = 2.26, 95% CI: 1.38 to 3.73). Daytime napping has been found to be causally related to a higher risk of NAFLD. Furthermore, across all participants, napping for an average duration over 30 minutes was linked to an elevated likelihood of NAFLD.

Improving Cancer Probability Estimation in Non-Diagnostic Bronchoscopies: A meta-analysis

BackgroundIn patients with peripheral pulmonary lesions (PPL), non-diagnostic bronchoscopy, results are not uncommon. The conventional approach to estimate the probability of cancer (pCA) following bronchoscopies relies on dichotomous test assumptions, utilizing prevalence, sensitivity, and specificity to determine negative predictive value (NPV). However, bronchoscopy is a multi-disease test, raising concerns about the accuracy of dichotomous methodologies. Research QuestionBy how much does calculating pCA using a dichotomous approach (pCAdichotomous) underestimate the true pCA when applied to multi-disease tests like bronchoscopy for the diagnosis of PPL? MethodsMeta-analysis of cohort studies involving radial-EBUS for PPL. PRISMA guidelines were followed, constructing 2×2 contingency tables for calculating pCAdichotomous. For the multi-disease test approach, 3×3 contingency tables for calculating pCAmulti-disease using the likelihood ratio method for non-diagnostic results LR(T0) was used. Observed malignancy rates in patients with non-diagnostic results were compared to pCAdichotomous and pCAmulti-disease. ResultsIn 46 studies (7506 patients), malignancy was the underlying diagnosis in 76%, another specific disease in 13%, and non-specific fibrosis/scar in 10%. The percentage of patients with non-diagnostic results who had malignancy matched pCAmulti-disease across all studies. In contrast, pCAdichotomous consistently underestimated cancer risk (median difference: 0.12, 25th−75th percentile: 0.06−0.23), particularly in studies with a higher prevalence of non-malignant disease. The pooled LR(T0) was 0.46 (95% CI 0.40−0.52, I2 76%, p<0.001), and correlated with the prevalence of non-malignant diseases (p=0.001). InterpretationConventional dichotomous methods for estimating pCA after non-diagnostic bronchoscopies underestimate the likelihood of malignancy. Physicians should opt for the multi-disease test approach when interpreting bronchoscopy results.

Palliative care and end stage liver disease: A survey study comparing perspectives of hepatology and palliative care physicians and clinical scenarios that could require palliative care intervention

Background and aimsThe prevalence and mortality of chronic liver disease has risen significantly. In end stage liver disease (ESLD) the survival of patients is approximately 2 years. Despite the poor prognosis and high symptom burden of these patients, integration of palliative care is reduced. We aim to analyze the agreement between palliative care and hepatology physicians of clinical scenarios that could require palliative care intervention. MethodsA cross-sectional study was conducted. Palliative care and hepatology physicians were surveyed. Using a five-point Likert scale, their perceptions of palliative care in ESLD were rated. Their agreement in clinical scenarios that could require palliative care intervention were evaluated. Analyses were conducted to assess any differences by primary role (hepatology vs. palliative care) and length of practice (<10 years vs. 10 years). ResultsA total of 123 responses were obtained: 52% from palliative care and 48% from hepatology. The majority (66.7%) work in the field for up to ten years. There was a great consensus in 4 of the 8 clinical scenarios. In scenarios with less consensus, the area of activity and length of practice influence the reliance of physicians on palliative care. Involvement of palliative care in ESLD was considered “rare” by 30% and 61% consider difficult to predict the prognosis. More than 90% support medical training in both areas of activity. ConclusionThe current involvement of palliative care is considered low, but there are clinical conditions that reveal a clear consensus and there's a unanimous view of the relevance of training.

Association between wet-bulb globe temperature and kidney function in different geographic regions in a large Taiwanese population study.

The worldwide prevalence and incidence rates of end-stage renal disease have been increasing, and the trend is pronounced in Taiwan. This is especially evident in southern Taiwan, where the wet-bulb globe temperature (WBGT) is consistently higher than in other regions. The association between kidney function and WBGT has not been fully investigated. Therefore, the aim of this study was to evaluate the association between estimated glomerular filtration rate (eGFR) and WBGT and variations in this association across different geographic regions in Taiwan. We used the Taiwan Biobank (TWB) to obtain data on community-dwelling individuals, linked these data with WBGT data obtained from the Central Weather Bureau and then processed the data using a machine learning model. WBGT data were recorded during the working period of the day from 8:00 a.m. to 5:00 p.m. These data were then compiled as 1-year, 3-year and 5-year averages, recorded prior to the survey year of the TWB of each participant. We identified 114483 participants who had WBGT data during 2012-2020. Multivariable analysis showed that, in northern Taiwan, increases in 1- and 3-year averages of WBGT during the working period (β=-0.092, P=.043 and β=-0.193, P<.001, respectively) were significantly associated with low eGFR. In southern Taiwan, increases in 1-, 3- and 5-year averages of WBGT during the working period (β=-0.518, P<.001; β=-0.690, P<.001; and β=-0.386, P=.001, respectively) were gnificantly associated with low eGFR. These findings highlight the importance of heat protection for people working outdoors or in high-temperature environments as a measure to prevent negative impacts on kidney function. Moreover, we observed that in southern Taiwan, every 1°C increase in WBGT had a greater impact on the decrease in eGFR compared with other regions in Taiwan.

The Epileptic Heart Syndrome: Epidemiology, pathophysiology and clinical detection

Population studies report elevated prevalence of cardiovascular disease in patients with chronic epilepsy. Multiple pathophysiologic processes have been implicated, including accelerated atherosclerosis, myocardial infarction, altered autonomic tone, heart failure, atrial and ventricular arrhythmias, and hyperlipidemia. These deleterious influences on the cardiovascular system have been attributed to seizure-induced surges in catecholamines and hypoxemic damage to the heart and coronary vasculature. Certain antiseizure medications can accelerate heart disease through enzyme-inducing increases in plasma lipids and/or increasing risk for life-threatening ventricular arrhythmias as a result of sodium channel blockade. In this review, we propose that this suite of pathophysiologic processes constitutes “The Epileptic Heart Syndrome.” We further propose that this condition can be diagnosed using standard electrocardiography, echocardiography, and lipid panels. The ultimate goal of this syndromic approach is to evaluate cardiac risk in patients with chronic epilepsy and to promote improved diagnostic strategies to reduce premature cardiac death.

Associations between leisure-time physical activity and the prevalence and incidence of osteoporosis disease: Cross-sectional and prospective findings from the UK biobank

BackgroundPrevious studies underscore the protective role of physical activity (PA) in bone health, yet the relationship between different PA categories and osteoporosis risk remains less explored. Understanding the relationships helps tailor health recommendations and policies to maximize the effects of preventing osteoporosis. MethodsThe cross-sectional study involves 488,403 UK Biobank participants with heel quantitative ultrasound-estimated bone mineral density (eBMD) data. The longitudinal cohort involves 471,394 UK Biobank participants without initial osteoporosis and with follow-up records. PA exposure categories in our study included sedentary behavior (SB), total PA (TPA), and different category-specific PA including household, leisure, and work PA. The cases of osteoporosis were assessed using the International Classification of Diseases, 10th revision (ICD-10). The linear, logistic, and Cox proportional hazard regression models were used in our study. ResultsIn the cross-sectional study, 15,818 (3.28 %) participants had osteoporosis. TPA levels have a positive correlation with eBMD and a negative correlation with osteoporosis prevalence. Among different categories of PA, higher levels of leisure PA were correlated with increased eBMD and a lower osteoporosis risk (leisure PA: OR: 0.83, 95 % CI: 0.79 to 0.86;). In the longitudinal study, 16,058 (17.6 % male, 82.4 % female) (3.41 %) individuals developed osteoporosis during an average follow-up of 13 years. We observed consistent protective effects of high levels of PA on osteoporosis incidence risk, particularly within the category of leisure PA (TPA: HR: 0.78, 95 % CI: 0.74 to 0.82; leisure PA:HR: 0.83, 95 % CI: 0.80 to 0.87). Such associations are independent of genetic predisposition, with no evidence of gene-PA interactions, and keep steady among individuals using drugs affecting bone-density. Moreover, among different leisure PA items, strenuous sports, other exercises, and walking for pleasure conferred a substantial protective effect against osteoporosis. Additionally, non-elderly individuals and males exhibited lower osteoporosis risk from PA. ConclusionThis study highlights activity categories differently associated with the risk of osteoporosis. Adherence to frequent leisure PA may have a protective effect against osteoporosis. Such associations are independent of genetic susceptibility to osteoporosis and keep steady among individuals using drugs affecting bone-density. This highlights that leisure PA could be suggested as a more effective intervention in the primary prevention of osteoporosis.

Underrepresentation of black individuals in pivotal trials for novel anticancer drugs: Potential consequence of using estimated creatinine clearance to assess kidney function?

BackgroundBlack individuals are historically underrepresented in oncology clinical trials. One potential reason for this is the prevalence of kidney disease in Black individuals, utilization of estimated creatinine clearance as a surrogate for glomerular filtration rate (GFR) in oncology, and GFR-based trial eligibility criteria. We characterized the representation of racial minorities in anticancer agent pivotal trials and examined if GFR-based trial eligibility criteria impact the proportion of Black individuals in trial populations. MethodsWe constructed a data repository for anticancer drugs FDA-approved 2015–2019 and associated pivotal trials, from which we extracted trial population racial compositions and GFR-based trial eligibility criteria. We calculated the participation-to-incidence ratio (PIR) and participation-to-mortality ratio (PMR) for a variety of cancer sites, where PIR or PMR >1.2 and < 0.8 indicate overrepresentation and underrepresentation, respectively. We evaluated the relationship between GFR eligibility cutoffs and the proportion of Black enrollees with Spearman rank correlation coefficient. ResultsWe assessed 24,698 patients in 74 trials. Black individuals were underrepresented in all trials (PIR ≤0.48, PMR ≤0.50). For trials with GFR-based eligibility criteria (n = 49), a lower GFR cutoff was modestly associated with a higher proportion of Black enrollees (r = −0.29, p = 0.039). This relationship was strengthened for trials that only used estimated creatinine clearance to estimate GFR (r = −0.43, p = 0.004). ConclusionsGFR-related eligibility, and specifically the use of estimated creatinine clearance, may contribute to Black individuals being disproportionately excluded from cancer clinical trials. This highlights the need for implementation of contemporary GFR equations and other interventions to boost racial minority trial enrollment.

Diagnostic and Prognostic Value of Machine Perfusion Biomarkers in Kidney Graft Evaluation

BackgroundWith the rising prevalence of end-stage kidney disease, the use of expanded criteria donor allografts, seen as essential for meeting organ demand, still proves challenging due to their higher risk of graft loss, delayed function, and rejection. Machine perfusion, a technique in preserving allografts, offers improved allograft outcomes compared to static cold storage while allowing for the noninvasive measurement of kidney injury biomarkers in the perfusate solution. This offers an objective method to assess graft function at various preservation stages. Materials and MethodsWe conducted a narrative review of the databases PubMed and Scopus, including studies written in the English language and published after 2010. ResultsIn this narrative review, we identified biomarkers, like 4-hydroxyproline, taurine, and glutathione transferase, as predictive markers of delayed graft function. Additionally, biomarkers, like extracellular histone h3, vascular cell adhesion protein, and matrix metalloprotease protein, have shown correlation with decreased graft function, although their predictive ability remains inconclusive. DiscussionThe review outlines various suggestions for potential areas of research focus to enhance future expanded criteria donor allograft utilization. However, limitations exist, including the absence of a singular reliable biomarker and the challenges of validating biomarker effectiveness across diverse outcomes.

The association of menopause with cardiometabolic disease risk factors in women living with and without HIV in sub-Saharan Africa: Results from the AWI-Gen 1 study

BackgroundMenopause and HIV are associated with cardiometabolic disease. In sub-Saharan Africa there is a growing population of midlife women living with HIV and a high prevalence of cardiometabolic disease. ObjectivesThe aim of this study was to determine whether menopause and HIV were associated with cardiometabolic disease risk factors in a population of midlife sub-Saharan African women. Study designThis was a cross-sectional comparison of cardiometabolic disease risk factors between 944 premenopausal women (733 living without HIV and 211 living with HIV) and 1135 postmenopausal women (932 living without HIV and 203 living with HIV) in sub-Saharan Africa.Main outcome measuresAnthropometric and cardiometabolic variables were compared between pre- and postmenopausal women living without HIV and between pre- and postmenopausal women living with HIV and between women living without HIV and women living with HIV. ResultsThe prevalence of HIV was 19.9 %. Age at menopause was lower in women living with HIV than in women living without HIV (48.1 ± 5.1 vs 50.9 ± 4.7 years, p < 0.001).Women living with HIV and receiving efavirenz-based antiretroviral therapy had a lower body mass index (BMI), hip circumference, blood pressure and carotid intima media thickness but higher triglyceride levels and insulin resistance than women living without HIV. Antiretroviral therapy-naïve women living with HIV had lower HDL-cholesterol than women living without HIV.In this study, menopause was associated with higher LDL-C levels, regardless of HIV status. ConclusionThe high prevalence of obesity and related cardiometabolic disease risk factors in these midlife sub-Saharan African women is not related to the menopausal transition. The association of cardiometabolic disease risk factors with HIV and antiretroviral therapy is complex and requires further investigation in longitudinal studies, as does the negative association of age at final menstrual period with HIV.

Prevalence of Progressive Fibrosing Interstitial Lung Disease in Patients with Primary Sjogren Syndrome.

Interstitial lung disease (ILD) represents a frequent cause of morbidity and mortality in primary Sjogren syndrome (pSS). However, the prevalence and behavior of pSS-ILD remains incomplete, largely based on retrospective heterogeneous studies. To investigate the prevalence of progressive pulmonary fibrosis (PPF) in a multicentric cohort of patients with pSS-ILD. Additionally, this study explored possible correlations between PPF and clinical, demographic, and serological features of pSS. All consecutive patients with pSS-ILD were enrolled in a 6-month period. Clinical, demographic, and serological features of pSS, other than functional and radiological lung features, were collected. Clinical behaviors of ILD other than PPF were also investigated. Seventy-two patients were enrolled. A fibrosing ILD pattern was observed in 65.3% of patients with pSS-ILD; among them, 55.3% showed a PPF. The radiologic pattern (NSIP, UIP, or others) was not associated with PPF; in particular, patients with PFF had UIP in 42.3% of cases and NSIP in 57.7%, without a significant difference with respect to the non-PPF group (p = 0.29). Shorter pSS disease duration, higher age at pSS diagnosis, and lower frequency of antinuclear antibodies were correlated with the PPF subgroup. However, multivariate analysis did not confirm these associations. This study provides valuable insights into the prevalence and characteristics of PPF in pSS-ILD. In particular, UIP and NSIP showed a similar evolution towards PPF in patients with pSS; for NSIP, this behavior was more frequent than for other rheumatic diseases. Our results emphasize the importance of early recognition of PPF for timely intervention and careful follow-up. This study provides valuable insights into the prevalence and characteristics of PPF in pSS-ILD. In particular, UIP and NSIP showed a similar evolution towards PPF in patients with pSS; for NSIP, this behavior was more frequent than for other rheumatic diseases. Our results emphasize the importance of early recognition of PPF for timely intervention and careful follow-up.

Lamivudine protects mice from gastric ulcer by activating PGK1 to suppress ferroptosis

Gastric ulcer is a highly prevalent digestive tract disease across the world, which is recurrent and hard to cure, sometimes transforming into gastric cancer if left untreated, posing great threat to human health. To develop new medicines for gastric ulcer, we ran a series of screens with ethanol stress model in GES-1 cells, and we uncovered that lamivudine rescued cells from ethanol toxicity. Then, we confirmed this discovery using the well-established ethanol-induced gastric ulcer model in mice and our findings suggest that lamivudine can directly activate phosphoglycerate kinase 1 (PGK1, EC 2.7.2.3), which binds and stimulates superoxide dismutase 1 (SOD1, EC 1.15.1.1) to inhibit ferroptosis and ultimately improve gastric ulcer. Moreover, AAV-PGK1 exhibited comparable gastroprotective effects to lamivudine. The findings are expected to offer novel therapeutic strategies for gastric ulcer, encompassing both lamivudine and AAV-PGK1

Stem Cell-Based or Cell-Free Gene Therapy in Chondrocyte Regeneration: Synovial Fluid-Derived Mesenchymal Stem Cell Exosomes.

Cartilage injuries are currently the most prevalent joint disease. Previous studies have emphasized the use of stem cells as the effective treatment for regenerating cartilage damage. In this study, considering the difficulties of the cellular therapy method, it was hypothesized that human synovial fluid-derived mesenchymal stem cell (hSFMSC) exosomes as a SC source could be used to treat these injuries as a safer and cell-free therapeutic alternative procedure due to its direct relevance to cartilage regeneration. Moreover, this study aimed to determine the miRNA and target genes required for the formation of SC treatment combined with gene therapy in order to reveal the mechanism of cartilage regeneration and increase its effectiveness. MSCs were characterized by flow cytometry, and immunocytochemical and differentiation analyses were done. To characterize functionally isolated exosomes, in vitro uptake analysis was performed. RT-qPCR was used to examine in terms of the advantages of cellular and cell-free therapy, mature human chondroblasts derived by differentiation from hSF-MSCs and human chondrocyte profiles were compared in order to demonstrate the above profile of hSF-MSCs and exosomes isolated from them, and the effectiveness of SC therapy in repairing cartilage damage. According to our findings, the expression level of hsa-miR-155-5p was found to be considerably higher in chondrocytes differentiated from human synovial fluid MSCs than in mature human chondrocytes. These findings were also supported by the TGF-signalling pathway and chondrogenesis marker genes. It was concluded that hSF-MSCs and exosomes can be used in the treatment of cartilage damage, and hsa-miR-155-5p can be used as a target miRNA in a new gene therapy approach because it increases the therapeutic effect on cartilage damage.