Subgroup Differences Research Articles

The Uselessness of Anaerobic Antibiotic Coverage in Aspiration Pneumonia: A Systematic Review and Meta-Analysis

Introduction: Asthma is a prevalent respiratory condition, and biologic agents have proven effective in managing moderate to severe asthma. However, the role of biomarkers in guiding the use of biologic agents remains unclear. Method: On July 30, 2024, a systematic review and subsequent meta-analysis were conducted by searching three major online databases: PubMed, Web of Science, and Cochrane. Results: The final analysis included 10 studies with a total of 6,709 patients with moderate to severe asthma. The overall pooled effect across all ages demonstrated a rate ratio (RR) reduction of 0.61 (95% CI: 0.46 to 0.80; p < 0.01; I² = 71%). Subgroup analysis revealed an onset or treated age of less than 18 years with RRs of 0.79 (95% CI: 0.62 to 1.02; p = 0.07; I² = 0%) and 0.88 (95% CI: 0.42 to 1.84; p = 0.73; I² = 14%), respectively. Patients with varying blood eosinophil levels showed a pooled RR of 0.51 (95% CI: 0.38 to 0.69; p < 0.01; I² = 82.7%). However, blood eosinophil levels below 150/μL demonstrated a limited effect of biologic agents, with an RR of 0.77 (95% CI: 0.35 to 1.67; p = 0.50; I² = 87%). For patients with all levels of fraction of exhaled nitric oxide (FeNO), the RR was 0.43 (95% CI: 0.30 to 0.62; p < 0.01; I² = 84%). The test for subgroup differences yielded a p-value of < 0.001, indicating that patients with higher FeNO levels experienced a more significant reduction in RR. Conclusion: Patients with asthma onset or treatment before age 18 may benefit less from biologics. Blood eosinophil counts and FeNO levels aid in selecting these therapies.

Comparison of Efficacy of Atorvastatin and Rosuvastatin in Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

Acute coronary syndrome (ACS) remains a leading cause of morbidity and mortality worldwide. Statins, particularly atorvastatin, and rosuvastatin, are crucial in managing cholesterol levels and reducing cardiovascular risk in ACS patients. However, direct comparative studies between these two statins are limited. This meta-analysis aimed to compare the efficacy of atorvastatin and rosuvastatin in reducing major adverse cardiovascular events (MACE) and all-cause mortality in patients with ACS. A comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, and Scopus for studies published up to July 2024. Randomized controlled trials and observational studies directly comparing atorvastatin and rosuvastatin in ACS patients were included. The primary outcomes were the incidence of MACE and all-cause mortality. Six studies involving 4195 patients were included in the meta-analysis. Pooled analysis showed no statistically significant difference between atorvastatin and rosuvastatin in reducing MACE [risk ratio (RR): 0.91, 95% confidence interval (CI): 0.68 to 1.22, p-value: 0.54] or all-cause mortality (RR: 0.94, 95% CI: 0.52 to 1.70, p-value: 0.83). No significant heterogeneity was observed among the studies (I-square: 0% for both outcomes). This meta-analysis suggests that atorvastatin and rosuvastatin have comparable efficacy in reducing MACE and all-cause mortality in ACS patients. These findings provide clinicians with flexibility in choosing between these statins based on individual patient factors. However, further large-scale randomized controlled trials are needed to confirm these results and explore potential differences in specific patient subgroups.

Serum uric acid and mortality in metabolic dysfunction-associated steatotic liver disease: Subgroup differences

Background and aimsThis study aims to investigate the association between serum uric acid (SUA) and both the risk and long-term mortality of dysfunction-associated steatotic liver disease (MASLD), and to explore differences between the pure MASLD and metabolic and alcohol related/associated liver disease (MetALD) subgroups. Methods and resultsWe included 11,675 participants from the Third National Health and Nutrition Examination Survey, with matched mortality data up to 2019. Logistic regression and Cox proportional hazards regression evaluated the relationship between SUA and both the risk and mortality of MASLD. Non-linear correlations and threshold effects were explored using restricted cubic splines and a two-piecewise Cox proportional hazards model. We found that SUA was positively associated with the risk of MASLD [odds ratio (OR): 1.19, 95 % confidence interval (CI) 1.12–1.27]. For pure MASLD, SUA showed a positive association with all-cause mortality [<4.7 mg/dL: hazard ratio (HR): 1.34, 95 % CI 1.04–1.73; ≥4.7 mg/dL: HR: 1.08, 95 % CI 1.02–1.15] and cardiovascular mortality (HR: 1.12, 95 % CI 1.02–1.22). For MetALD, there was an inverse J-shaped relationship (threshold: 6.6 mg/dL) between SUA and all-cause mortality. Below the threshold, SUA was negatively correlated with all-cause mortality (HR: 0.42, 95 % CI 0.19–0.93), but no association was found above it (HR: 0.81, 95 % CI 0.54–1.21). Additionally, no association was observed between SUA and cardiovascular mortality. ConclusionsSUA serves as an independent predictor of the risk and all-cause mortality of MASLD. The relationship between SUA and both all-cause and cardiovascular mortality differs between the pure MASLD and MetALD subgroups.

Regional Heterogeneity of the Results of Glucagon-Like Peptide 1 Receptor Agonist Trials in Type 2 Diabetes: A Reanalysis of Individual Participant Data.

Multiregional trials are designed under the assumption that treatment effect applies to the entire target population, yet several factors may introduce geographic heterogeneity in treatment effect. We explored whether such variations exist in trials assessing the efficacy of glucagon-like peptide 1 receptor agonists (GLP-1RAs) in major cardiovascular events (MACE) in type 2 diabetes. A systematic search of Medline and the Cochrane Library was conducted from inception until 30 June 2020. We included international randomized controlled trials comparing any GLP-1RA versus placebo, with MACE as a primary end point. Individual participant data were subsequently requested from the sponsor or through data sharing platforms. For each trial, we calculated hazard ratios (HRs) and their 95% CIs for MACE, subgrouped by region. We then performed a random-effects meta-analysis and conducted meta-regressions to assess the influence of predetermined variables of interest on treatment effect. We included six trials including 45,426 patients. Baseline risk of MACE ranged from 2.9 per 100 patient-years in Southern Asia to 7.4 per 100 patient-years in Sub-Saharan Africa. HRs for MACE ranged between 0.25 (95% CI 0.05, 1.12) in Northern Africa to 0.98 (0.79, 1.22) in Western Europe. There was no significant subgroup difference across regions (P = 0.70). Baseline risk of MACE and indexes of development status (i.e., Human Development Index, gross domestic product) were independently associated with GLP-1RA efficacy. This study does not suggest any regional heterogeneity of GLP-1RA efficacy in MACE. However, a higher baseline risk and lower development status were associated with a greater benefit of these drugs.

N-acetylcysteine as a treatment for substance use cravings: A meta-analysis.

N-acetylcysteine (NAC) may serve as a novel pharmacotherapy for substance use and substance craving in individuals with substance use disorders (SUDs), possibly through its potential to regulate glutamate. Though prior meta-analyses generally support NAC's efficacy in reducing symptoms of craving, individual trials have found mixed results. The aims of the this updated meta-analysis were to (1) examine the efficacy of NAC in treating symptoms of craving in individuals with a SUD and (2) explore subgroup differences, risk of bias, and publication bias across trials. Database searches of PubMed, Cochrane Library, and ClinicalTrials.gov were conducted in June and July of 2023 to identify relevant randomized control trials (RCTs). The meta-analysis consisted of 9 trials which analyzed data from a total of 623 participants. The most targeted substance in the clinical trials was alcohol (3/9; 33.3%), followed by tobacco (2/9; 22.2%) and multiple substances (2/9; 22.2%). Meta-analysis, subgroup analyses, and leave-one-out analyses were conducted to examine treatment effect on craving symptoms and adverse events (AEs). Risk of bias assessments, Egger's tests, and funnel plot tests were conducted to examine risk of bias and publication bias. NAC did not significantly outperform placebo in reducing symptoms of craving in the meta-analysis (SMD = 0.189, 95% CI = -0.015 - 0.393). Heterogeneity was very high in the meta-analysis (99.26%), indicating that findings may have been influenced by clinical or methodological differences in the study protocols. Additionally, results indicate that there may be publication bias present. Overall, our findings are contrary to those of prior meta-analyses, suggesting limited impact of NAC on substance craving. However, the high heterogeneity and presence of publication bias identified warrants cautious interpretation of the meta-analytic outcomes.

Association between prediabetes and the incidence of gastric cancer: A meta-analysis.

Prediabetes has been found to be associated with an elevated overall risk of cancer, which may be site-specific. we performed a protocol for systematic review and meta-analysis to investigate the correlation between prediabetes and the incidence of gastric cancer (GC). A thorough review of the literature was conducted in the PubMed, Embase, and Web of Science databases to identify pertinent observational studies with longitudinal follow-up. The random-effects model was employed to consolidate the data, taking into account the potential impact of heterogeneity. A total of 13 datasets from 8 prospective cohort studies were included. The prevalence of prediabetes was 9.6%. During the mean follow-up duration of 7.1 to 12.2 years, 33,135 patients were diagnosed with GC. According to the results of the pooled analysis, prediabetes was associated with a mildly higher incidence of GC over time (risk ratio: 1.07, 95% confidence interval: 1.01-1.13, P = .03; I2 = 44%). Subsequent subgroup analyses indicated that the relationship between prediabetes and the heightened risk of GC may not be substantially influenced by factors such as the country in which the study was conducted, the average age of participants, their gender, the definition of prediabetes used, the prevalence of prediabetes at the beginning of the study, the incidence of GC within the studied population, or the adjustment made for body mass index (P for subgroup difference all >.05). The presence of prediabetes may increase the risk of GC by a mild amount when compared with people with normoglycemia in community-derived adult populations.

Outcomes and Practices of Endotracheal Intubation Using the Glasgow Coma Scale in Acute Non-Traumatic Poisoning: A Systematic Review and Meta-Analysis of Proportions.

Acute poisoning often results in decreased consciousness, necessitating airway assessment and management. Existing literature in the trauma setting suggests the importance of airway protection in unconscious patients to prevent complications, including aspiration. Practices for endotracheal intubation in non-traumatic acute poisoning are poorly described and variable, particularly regarding the use of a Glasgow Coma Scale (GCS) ≤ 8 threshold for intubation. A systematic review and meta-analysis of proportions was conducted to evaluate intubation rates and outcomes in patients presenting for acute non-traumatic poisoning. Studies were excluded if the primary indication for intubation was not airway protection. We analyzed rates of intubation, mortality, and aspiration by subgrouping patients into GCS ≤ 8, GCS 9-15, or mixed GCS. Common and random-effects analysis were used, supplemented by subgroup analyses. 39 studies were included in the analysis, involving 15,959 patients. Random-effects pooled intubation rates varied significantly across GCS categories: GCS ≤ 8 (30.0%, I2 = 92%, p < 0.01), GCS 9-15 (1.0%, I2 = 0%, p = 0.91), and mixed GCS (11.0%, I2 = 94%, p < 0.01), p-value <0.01 for subgroup difference. Aspiration rates also varied: GCS ≤ 8 (19.0%, I2 = 84%, p < 0.01), GCS 9-15 (4.0%, I2 = 78%, p < 0.01), and mixed group (5.0%, I2 = 72%, p < 0.01), p-value <0.01 for subgroup difference. Mortality rates remained low across all groups: GCS ≤ 8 (1.0%, I2 = 0%, p = 0.62), GCS 9-15 (1.0%, I2 = 0%, p = 0.99), and mixed group (2.0%, I2 = 68%, p < 0.01). The conventional "less than 8, intubate" approach may not be directly applicable to acute poisoning patients due to heterogeneity in patient presentation, intubation practices, and low mortality. Therefore, a nuanced approach is warranted to optimize airway management strategies tailored to individual patient needs.

Parvalbumin expression does not account for discrete electrophysiological profiles of glutamatergic ventral pallidal subpopulations

The ventral pallidum (VP) has emerged as a critical node in the mesolimbic reward system. Modulating the VP can impact the subjective valuation of rewards, reward motivation, and reward seeking under conflict, making it an attractive target for clinical neuromodulation therapies that manage substance use disorders. To understand how to rationally modulate the VP, we need a better understanding of the electrophysiological properties of VP neurons and the molecular and biophysical determinants of these properties. Here, we used patch-clamp electrophysiology to characterize the intrinsic properties of glutamatergic VP (VPGlu) neurons and observed two distinct electrophysiological profiles: VPGlu neurons that undergo depolarization block in response to progressively increasing current injection amplitudes and those that were resistant to depolarization block. To explore the mechanisms that could contribute to these distinct profiles, we used targeted ribosome affinity purification to identify ion channel subunits and regulatory proteins by isolating actively transcribed mRNA selectively from VPGlu neurons. We then used this transcriptomic information to implement a Markov Chain Monte Carlo method to parameterize a large population of biophysically distinct multicompartment models of VPGlu neurons conforming to either subpopulation. Based on prior literature suggesting parvalbumin (PV) is expressed in a subset of VPGlu neurons, and that PV expression governs the firing properties of those neurons, we tested the hypothesis that PV expression accounted for differences in subgroups, by increasing the maximal firing frequency and conferring resistance to depolarization block. In contrast, our model determined that PV expression at physiological levels had no effect on maximum firing rate. However, supraphysiological expression levels of PV appeared to induce a depolarization block in previously depolarization block-resistant neuron models, suggesting that other intracellular calcium-binding proteins could play a role in determining the firing phenotype of VPGlu neurons. We corroborated this result with single-cell patch-clamp RT-PCR, which confirmed that PV expression did not distinguish the two electrophysiologically distinct subpopulations. Together, these findings establish that VPGlu neurons are composed of biophysically distinct subpopulations that have not been appreciated in prior studies interrogating the function of this population. With the advent of novel tools for cell-type specific pharmacology and targeted neurostimulation, this understanding will be critical for developing strategies to rationally modulate VPGlu cells to treat disorders characterized by maladaptive reward seeking.

Altered Function and Structure of the Cerebellum Associated with Gut-Brain Regulation in Crohn's Disease: a Structural and Functional MRI Study.

This study employed structural and functional magnetic resonance imaging (MRI) to investigate changes in the function and structure of the cerebellum associated with gut-brain axis (GBA) regulation in patients diagnosed with Crohn's disease (CD). The study comprised 20 CD patients, including 12 with active disease (CD-A) and 8 in remission (CD-R), as well as 21 healthy controls. Voxel-based morphometry (VBM) was utilized for structural analysis of cerebellar gray matter volume, while independent component analysis (ICA) was applied for functional analysis of cerebellar functional connectivity (FC). The results showed significant GMV reduction in the left posterior cerebellar lobe across all CD patients compared to HCs, with more pronounced differences in the CD-A subgroup. Additionally, an increase in mean FC of the cerebellar network was observed in all CD patients, particularly in the CD-A subgroup, which demonstrated elevated FC in the vermis and bilateral posterior cerebellum. Correlation analysis revealed a positive relationship between cerebellar FC and the Crohn's Disease Activity Index (CDAI) and a trend toward a negative association with the reciprocal of the Self-rating Depression Scale (SDS) score in CD patients. The study's findings suggest that the cerebellum may play a role in the abnormal regulation of the GBA in CD patients, contributing to a better understanding of the neural mechanisms underlying CD and highlighting the cerebellum's potential role in modulating gut-brain interactions.

Telehealth-Supported Exercise or Physical Activity Programs for Knee Osteoarthritis: Systematic Review and Meta-Analysis.

The integration of telehealth-supported programs in chronic disease management has become increasingly common. However, its effectiveness for individuals with knee osteoarthritis (KOA) remains unclear. This study aimed to assess the effectiveness of telehealth-supported exercise or physical activity programs for individuals with KOA. A comprehensive literature search encompassing Embase, MEDLINE, CENTRAL, Web of Science, PubMed, Scopus, PEDro, GreyNet, and medRxiv from inception to September 2023 was conducted to identify randomized controlled trials comparing telehealth-supported exercise or physical activity programs to a control condition for KOA. Data were extracted and qualitatively synthesized across eligible studies, and a meta-analysis was performed to evaluate the effects. The study was reported according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020. In total, 23 studies met eligibility criteria, with 20 included in the meta-analysis. Results showed that telehealth-supported exercise or physical activity programs reduced pain (g=-0.39; 95% CI -0.67 to -0.11; P<.001), improved physical activity (g=0.13; 95% CI 0.03-0.23; P=.01), and enhanced physical function (g=-0.51; 95% CI -0.98 to -0.05; P=.03). Moreover, significant improvements in quality of life (g=0.25; 95% CI 0.14-0.36; P<.001), self-efficacy for pain (g=0.72; 95% CI 0.53-0.91; P<.001), and global improvement (odds ratio 2.69, 95% CI 1.41-5.15; P<.001) were observed. However, self-efficacy for physical function (g=0.14; 95% CI -0.26 to 0.53; P=.50) showed insignificant improvements. Subgroup analyses based on the World Health Organization classification of digital health (pain: χ22=6.5; P=.04 and physical function: χ22=6.4; P=.04), the type of teletechnology in the intervention group (pain: χ24=4.8; P=.31 and function: χ24=13.0; P=.01), and active or inactive controls (pain: χ21=5.3; P=.02 and physical function: χ21=3.4; P=.07) showed significant subgroup differences. Telehealth-supported exercise or physical activity programs might reduce knee pain and improve physical activity, physical function, quality of life, self-efficacy, and global improvement in individuals with KOA. Future research should consider longer implementation durations and assess the feasibility of incorporating wearables and standardized components into large-scale interventions to evaluate the effects. PROSPERO CRD42022359658; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=359658.

Effects of Contextualization on Subgroup Differences and Applicant Perceptions

Effects of Contextualization on Subgroup Differences and Applicant Perceptions

Sexual Orientation Differences in Age of First Treatment for a Mental Health Diagnosis: A Population-Based Study of Childhood and Adolescence

The aim of the current study was to identify the age at which sexual orientation disparity in mental health diagnoses can be first identified, as well as gender and sexual identity subgroup differences in such treatment, in a population-based sample. Young people aged 16 to 25 (N= 10,365) participating in the probability-based Swedish National Public Health Survey in 2018 were included. This sample was linked to physician-assessed mental health care treatment history data starting when all participants were 8 years old using national health care registries. Participants reporting a sexual minority identity in adolescence and young adulthood were more than 3 times as likely to have been treated for an internalizing disorder diagnosis (eg, depression, anxiety) and more than twice as likely to have been treated for a neurodevelopmental disorder diagnosis during childhood than participants reporting a heterosexual identity. Sexual minority participants overall and women in particular were more likely to have been treated for an internalizing disorder diagnosis at an early age compared with heterosexual participants, with this disparity starting at age 13. The sexual orientation disparity in likelihood of treatment for a neurodevelopmental disorder diagnosis was particularly elevated among bisexual/pansexual women with this disparity starting in early/middle adolescence. This population-based study linked to physician-assessed mental health diagnoses during childhood and adolescence identifies the age at which sexual orientation differences in treatment for common mental disorders emerge. The early emergence of this disparity suggests a potential benefit of interventions that facilitate social belonging for all youth.

P2Y12 Inhibitor Monotherapy After Short DAPT in Acute Coronary Syndrome: A Systematic Review and Meta-analysis.

P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) may balance ischemic and bleeding risks in patients with acute coronary syndrome (ACS). However, it remains uncertain how different P2Y12 inhibitors used as monotherapy affect outcomes. Randomized controlled trials comparing P2Y12 inhibitor monotherapy after a short course of DAPT (≤3 months) versus 12-month DAPT in ACS were included. The primary endpoint was major adverse cardiovascular events (MACE). All analyses included an interaction term for the P2Y12 inhibitor used as monotherapy. Trial sequential analysis were run to explore whether the effect estimate of each outcomes may be affected by further studies. Seven trials encompassing 27,284 ACS patients were included. Compared with 12-month DAPT, P2Y12 inhibitor monotherapy after a short course of DAPT was associated with no difference in MACE (OR 0.92, 95% CI 0.76-1.12) and a significant reduction in net adverse clinical events (NACE) (OR 0.75; 95% CI 0.60-0.94), any bleeding (OR 0.54, 95% CI 0.43-0.66) and major bleeding (OR 0.47, 95% CI 0.37-0.60). Significant interactions for subgroup difference between ticagrelor and clopidogrel monotherapy were found for MACE (pint=0.016), all-cause death (pint=0.042), NACE (pint=0.018), and myocardial infarction (pint=0.028). Trial sequential analysis showed conclusive evidence of improved NACE with ticagrelor, but not with clopidogrel monotherapy, compared with standard DAPT. In patients with ACS, P2Y12 inhibitor monotherapy after short DAPT halves bleeding without increasing ischemic events compared with standard DAPT. Ticagrelor, but not clopidogrel monotherapy, reduced MACE, NACE and mortality compared with standard DAPT, supporting its use after aspirin discontinuation. Protocol registration: This study is registered in PROSPERO (CRD42023494797).

Associations of Pap test utilisation with comorbidity and functional impairment among middle-aged non-Hispanic black women in the USA: a cross-sectional analysis of the 2018 BRFSS data

ObjectivesLimited evidence exists on the association of Pap test utilisation with comorbidity and functional impairment among middle-aged non-Hispanic black (NHB) women in the USA. We aimed to assess whether middle-aged...

Upper Limb Robots for Recovery of Motor Arm Function in Patients With Stroke: A Systematic Review and Meta-Analysis.

Robot technology to support upper limb (UL) rehabilitation poststroke has rapidly developed over the past 3 decades. We aimed to assess the effects of UL-robots (UL-RTs) on recovery of UL motor functioning and capacity poststroke when compared with any non-UL-RT and to identify variables that are associated with the found effect sizes (ESs). Randomized controlled trials (RCTs) comparing UL-RTs with any other intervention on patients with UL limitations poststroke were identified in electronic searches from PubMed, Wiley/Cochrane Libraries, Embase, Cumulative Index of Nursing and Allied Health Literature, Web of Science, SportDISCUS, Physiotherapy Evidence Database (PEDro), and Google Scholar from inception until August 1, 2022. Two reviewers independently extracted relevant data using a Microsoft Excel spreadsheet. Meta-analyses were performed for measures of UL-muscle synergism, muscle power, muscle tone, capacity, self-reported motor performance, and basic activities of daily living (ADLs). Subgroup, sensitivity, and meta-regression analyses were applied to identify factors potentially associated with found ESs. Analyses were performed using Review Manager version 5.4 or IBM SPSS statistics version 27. Ninety RCTs (N = 4,311) were included (median PEDro score 6 [6-7]). Meta-analyses of 86 trials (N = 4,240) showed small significant improvements in UL-muscle synergism (Fugl-Meyer Assessment of the UL [FM-UL]) (mean difference 2.23 [1.11-3.35]), muscle power (standardized mean difference [SMD] 0.39 [0.16-0.61]), motor performance (SMD 0.11 [0.00-0.21]), and basic ADLs (SMD 0.28 [0.10-0.45]). No overall effects were found for muscle tone (SMD -0.1 [-0.26 to 0.07]) or UL-capacity (SMD 0.04 [-0.10 to 0.18]), except with exoskeletons (SMD 0.27 [0.10-0.43]). Meta-regressions showed a significant positive association between baseline mean FM-UL and ESs for UL-capacity (r = 0.339; p = 0.03), in particular in the acute and early-subacute phases poststroke (r = 0.65; p = 0.01). No further significant subgroup differences or associations were found in our analyses. The small significant effects found at the level of motor impairment do not show generalization to clinically meaningful effects at the level of UL-capacity. Meta-regressions suggest that selected participants with some potential of UL-recovery may benefit most from UL-RT, especially earlier poststroke. The robustness and consistency of our findings suggest that the development of the next generation of UL-RT needs to be guided by a better mechanistic understanding about assumed underlying interaction effects between motor learning and motor recovery poststroke. A prospectively registered study protocol is available in the PROSPERO database under ID CRD42020197450.

Prediabetes and the treatment outcome of tuberculosis: A meta-analysis.

Diabetes has been related to higher risk and poor prognosis of patients with tuberculosis, while the influence of prediabetes on the treatment outcome of patients with tuberculosis remains not determined. A meta-analysis was performed to evaluate the influence of prediabetes on treatment outcome of patients with tuberculosis. Relevant cohort studies were acquired through a search of Medline, Embase, and Web of Science databases. To minimise the influence of between-study heterogeneity, a randomised-effects model was used to pool the results. Eight prospective cohort studies including 3001 patients with tuberculosis were available for the meta-analysis. Among them, 752 (25.1%) were with prediabetes at baseline, and the patients were followed for a mean duration of 17.7 months. It was shown that compared to patients with normoglycemia, those with prediabetes were associated with a higher incidence of unfavourable treatment outcome (risk ratio [RR]: 1.41, 95% confidence interval [CI]: 1.02 to 1.96, p = 0.04; I2 = 56%). Subgroup analysis did not support that difference in study country (Asian or non-Asian), diagnosis (pulmonary tuberculosis only or also with extrapulmonary tuberculosis), mean age, follow-up duration, or study quality score had significant influence on the results (p for subgroup difference all >0.05). However, prediabetes at baseline was not associated with an increased risk of all-cause mortality during follow-up (RR: 1.59, 95% CI: 0.75 to 3.38, p = 0.23; I2 = 54%). Patients with tuberculosis and prediabetes may have a higher risk of unfavourable treatment outcome compared to patients with normoglycemia.

Effectiveness of Technology-Delivered Psychosocial Interventions for Family Caregivers of Patients With Dementia: A Systematic Review, Meta-Analysis and Meta-Regression.

Family caregivers living with patients with dementia (PwD) face psychological challenges due to care burden. Technology-delivered psychosocial interventions (TPIs) have played a promising role in improving health outcomes among family caregivers living with PwD. This review aims to synthesise evidence of the effectiveness of TPIs on primary (burden and depression) and secondary outcomes (self-efficacy, stress and anxiety) for family caregivers living with PwD. Random-effects meta-analyses were performed to determine effect size. Using Cochran's Q and I2 tests, statistical heterogeneity was evaluated. Sensitivity, subgroup analyses and meta-regression were employed to explain statistical heterogeneity. Twenty-eight trials comprising 4160 family caregivers from eight countries were included. Our meta-analysis revealed that TPIs resulted in slight reduction in depression, probably resulted in a slight reduction in burden and anxiety and slight increase in self-efficacy. Subgroup differences were detected in geographical regions (Western Pacific and Southeast Asia) for burden. While there were no significant subgroup differences in other factors, TPIs with preventive function and mobile applications had a more prominent larger effect size. Meta-regression analysis showed that attrition rate was a significant moderator on depression. Results are limited by the high risk of bias of included trials, which may reduce certainty of evidence. This review suggest TPIs are recommended as an adjunct treatment for alleviating burden and depressive outcomes in healthcare institutions. PROSPERO Registration Number: PROSPERO (CRD42023387962).

Metabolic activity of CYP2C19 and CYP2D6 on antidepressant response from 13 clinical studies using genotype imputation: a meta-analysis

Cytochrome P450 enzymes including CYP2C19 and CYP2D6 are important for antidepressant metabolism and polymorphisms of these genes have been determined to predict metabolite levels. Nonetheless, more evidence is needed to understand the impact of genetic variations on antidepressant response. In this study, individual clinical and genetic data from 13 studies of European and East Asian ancestry populations were collected. The antidepressant response was clinically assessed as remission and percentage improvement. Imputed genotype was used to translate genetic polymorphisms to metabolic phenotypes (poor, intermediate, normal, and rapid+ultrarapid) of CYP2C19 and CYP2D6. CYP2D6 structural variants cannot be imputed from genotype data, limiting the determination of metabolic phenotypes, and precluding testing for association with response. The association of CYP2C19 metabolic phenotypes with treatment response was examined using normal metabolizers as the reference. Among 5843 depression patients, a higher remission rate was found in CYP2C19 poor metabolizers compared to normal metabolizers at nominal significance but did not survive after multiple testing correction (OR = 1.46, 95% CI [1.03, 2.06], p = 0.033, heterogeneity I2 = 0%, subgroup difference p = 0.72). No metabolic phenotype was associated with percentage improvement from baseline. After stratifying by antidepressants primarily metabolized by CYP2C19, no association was found between metabolic phenotypes and antidepressant response. Metabolic phenotypes showed differences in frequency, but not effect, between European- and East Asian-ancestry studies. In conclusion, metabolic phenotypes imputed from genetic variants using genotype were not associated with antidepressant response. CYP2C19 poor metabolizers could potentially contribute to antidepressant efficacy with more evidence needed. Sequencing and targeted pharmacogenetic testing, alongside information on side effects, antidepressant dosage, depression measures, and diverse ancestry studies, would more fully capture the influence of metabolic phenotypes.

Budesonide Versus Mesalamine in Microscopic Colitis: A Comparative Meta-analysis of Randomized Controlled Trials.

Microscopic colitis (MC) is an inflammatory bowel disease of autoimmune origin that causes chronic watery diarrhea. Medications, including budesonide, mesalamine, loperamide, cholestyramine, and bismuth subsalicylate, are first-line therapies. Meanwhile, azathioprine, 6-mercaptopurine, and methotrexate are indicated for refractory MC. We aim to assess the efficacy and safety of budesonide compared with mesalamine for induction of remission in MC patients. We searched the Cochrane Library, Scopus, Web of Science, and PubMed for relevant clinical trials comparing either mesalamine or budesonide with a control group. We included the following outcomes: clinical remission (3 or fewer stools/day), daily stool weight, daily stool frequency, number of patients with clinical response <50% in the disease activity, and daily stool consistency. Safety end points included: any adverse event, serious adverse events, any adverse event-related discontinuation, abdominal discomfort, constipation, flatulence, nausea, dizziness, headache, bronchitis, nasopharyngitis, and depression. We conducted a meta-analysis model using the generic inverse variance method and performed a subgroup analysis based on the intervention administered. Nineteen randomized clinical trials were included. We found that after 6 weeks of follow-up, budesonide is associated with increased clinical remission rates compared with mesalamine [RR=2.46 (2.27, 2.67), and RR=2.24 (1.95, 2.57), respectively]. However, the test of subgroup difference revealed that the difference is not significant (P=0.25). After 8 weeks of follow-up, budesonide showed significantly higher clinical remission rates than mesalamine RR=2.29 (2.14, 2.45), and RR=1.7 (1.41, 2.05), respectively (P=0.003). Regarding the daily stool weight, patients in the budesonide group showed nonsignificant less stool weight [MD=-351.62 (-534.25, -168.99)] compared with mesalamine [MD=-104.3 (-372.34, 163.74)], P=0.14. However, daily stool frequency was significantly less in the budesonide group compared with mesalamine (P<0.001). Budesonide is associated with a significantly lower incidence of adverse events compared with mesalamine (P=0.002). Analysis of other safety endpoints was not significant between both groups. Budesonide was found to be better than mesalamine in MC patients in terms of clinical remission rate, especially after 8 weeks of follow-up. Budesonide also showed less incidence of adverse events. There is an urgent need for randomized, double-blinded clinical trials to provide direct and reliable evidence.

Serum Cytokeratin-18 levels as a prognostic biomarker in advanced liver disease: a comprehensive meta-analysis

Cytokeratin-18 (CK-18) is a marker of hepatic cell death. Serum CK-18 could serve as a prognostic marker for patients with advanced liver disease (ALD). This meta-analysis aims to explore the association between total CK-18 (M65) and caspase-cleaved CK-18 (M30) levels with the prognosis of ALD patients. Relevant longitudinal observational studies were identified through comprehensive searches of the Medline, Web of Science, and Embase databases. A random-effects model was utilized to synthesize the findings, accommodating heterogeneity among studies. The analysis included 14 datasets from 11 studies. Elevated serum CK-18 levels at admission were linked to a higher risk of death or liver transplantation during follow-up. This association was consistent for both M65 (risk ratio [RR] 1.99, 95% confidence interval [CI] 1.65 to 2.40, p < 0.001; I2 = 43%) and M30 (RR 1.94, 95% CI 1.57 to 2.40, p < 0.001; I2 = 46%). Subgroup analysis revealed that the relationship between serum M65 levels and adverse outcomes was attenuated in studies using multivariate analysis compared to those using univariate analysis (RR 1.78 vs. 2.80, p for subgroup difference = 0.03). Further subgroup analyses indicated that the prognostic significance of CK-18 for ALD patients was not significantly influenced by study design, methods of determining CK-18 cutoff values, or follow-up durations. Elevated serum CK-18 levels at admission indicate a poor prognosis in patients with ALD. This finding holds for both M65 and M30.