We sought to determine the prevalence of strabismus and the esotropia/exotropia ratio in Down syndrome. Wide ranges of an increased strabismus prevalence have been reported and it is unclear by how much esotropia exceeds exotropia in people with Down syndrome.

We compiled in a systematic review and meta-analysis results of over 100 studies that report the strabismus prevalence and ratio of esotropia/exotropia in cohorts of Down syndrome. We calculated the pooled global prevalence and established the geographical distribution of the strabismus prevalence and the esotropia/exotropia ratio.

The ethnically-adjusted global prevalence of strabismus in Down syndrome is 30.2%. In subjects 15 years and older, the global prevalence is 53.2%, and the lifetime prevalence is 51.0%. In populations which normally have more esotropia than exotropia (e.g. Caucasians), Down syndrome subjects have a further increased bias towards esotropia. In populations which normally have more exotropia (e.g. West Africans, Asians and Hispanics), Down syndrome subjects have a significantly lower esotropia/exotropia ratio (3.21) than reported in Caucasians with Down syndrome (9.98).

Worldwide, about 1.81 million people with Down syndrome have strabismus: 1.42 million of them have esotropia, and 0.37 million have exotropia. Differences in the esotropia/exotropia ratio between ethnicities point to the orbital anatomy as a major contributing factor to the etiology of strabismus in Down syndrome. The narrow-set eyes (reduced orbital width) in Down syndrome favor esotropia over exotropia, especially in Caucasians, thus explaining why Down syndrome patients from different ethnicities have different prevalences of esotropia and exotropia.

To estimate the association between abatacept use and the incidence of malignancy excluding non-melanomatous skin cancers (NMSCs).

Systematic database searches were performed, to April 2024, to identify phase II/III/IV randomized clinical trials (RCTs), long-term extension (LTE) and observational cohort studies of abatacept in people with rheumatoid arthritis and psoriatic arthritis. Network and pairwise meta-analyses were performed to estimate incidence rate ratios (IRRs) for malignancy excluding NMSC, comparing abatacept with placebo and tumour necrosis factor inhibitors (TNFi) in RCT/LTE studies. Pairwise meta-analyses evaluated the same outcome in observational studies, comparing abatacept with conventional synthetic DMARDs (csDMARDs) and biologic/targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs).

In 18 eligible RCTs and 10 LTE studies, there were 15 535 person-years of exposure to abatacept, 1495 to placebo and 733 to TNFi. In network meta-analyses of combined RCT/LTE data, the incidence of all malignancies excluding NMSCs was not significantly different between abatacept and placebo (IRR 0.58; 95% CI 0.32-1.09) or TNFi (IRR 0.72; 95% 0.27-1.87). In observational data, the incidence of malignancy was higher with abatacept, relative to other b/tsDMARDs (IRR 1.21; 95% CI 1.15-1.28), but not significantly different compared with csDMARDs (IRR 0.97; 95% CI 0.90-1.06).

Abatacept was associated with a higher incidence of malignancy compared with other b/tsDMARDs in observational studies, but not when compared with placebo or TNFi in RCT/LTE data. Further pharmacovigilance data is essential to help elucidate whether abatacept modifies cancer risk.

CRD42023382314.

We conducted a systematic review with pairwise (PMA) and network meta-analyses (NMA) to evaluate sodium-glucose transport protein 2 inhibitor (SGLT2i) effects in patients with both heart failure (HF) and type 2 diabetes mellitus (T2DM). Five databases were searched up to April 15, 2025. Primary outcomes were all-cause mortality (ACM), cardiovascular death (CVD), all-cause hospitalization (ACH), and hospitalization for heart failure (HHF). SGLT2i class effects versus control were assessed via PMA and individual SGLT2i comparative efficacy via NMA plus ranking using p-scores. Seventeen randomized controlled trials (n = 17,809) were included. Arms included canagliflozin (n = 2), dapagliflozin (n = 6), empagliflozin (n = 6), ertugliflozin (n = 1), ipragliflozin (n = 1), sotagliflozin (n = 1), placebo (n = 13), and standard of care (n = 4). Compared to control, SGLT2i significantly reduced ACM (HR 0.87, 95 %CI 0.78 to 0.98, low quality of evidence [QoE]), ACH (HR 0.74, 95 %CI 0.62 to 0.88, high QoE), and HHF (HR 0.70, 95 %CI 0.63 to 0.77, low QoE); but not CVD (HR 0.87, 95 %CI 0.76 to 1.00, very low QoE). Canagliflozin ranked highest in decreasing ACM (p-score = 0.86), CVD (p-score = 0.82), and HHF (p-score = 0.88). In patients with HF and T2DM, SGLT2i class effects include ACM, ACH, and HHF reduction. Among SGLT2i, canagliflozin showed greatest ACM, CVD, and HHF benefit.

Gut-brain neuromodulators might be efficacious for irritable bowel syndrome (IBS), but there has been no synthesis of evidence from randomised controlled trials (RCTs) of some drug classes, and whether they have pain-modifying properties in IBS is unclear. We updated a previous systematic review and meta-analysis of RCTs examining these questions.

We searched MEDLINE (from Jan 1, 1946, to Jan 1, 2025), Embase and Embase Classic (from Jan 1, 1947, to Jan 1, 2025), and the Cochrane Central Register of Controlled Trials (from database inception to Jan 1, 2025). Trials recruiting adults with IBS and that compared gut-brain neuromodulators versus placebo over at least 4 weeks of treatment were eligible. Dichotomous symptom data were pooled using a random effects model to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% CI.

The search strategy identified 3625 citations. 28 RCTs were eligible containing 2475 patients. Ten RCTs were identified since our previous meta-analysis, containing 1348 patients. The RR of global IBS symptoms not improving with gut-brain neuromodulators versus placebo in 22 RCTs (2222 patients) was 0·77 (95% CI 0·69-0·87). The best evidence in terms of persistence of global IBS symptoms was for tricyclic antidepressants (TCAs) in 11 trials (1144 patients; RR 0·70, 0·62-0·80). The RR of abdominal pain not improving with gut-brain neuromodulators versus placebo in 19 RCTs (1792 patients) was 0·72 (95% CI 0·62-0·83). The best evidence was for TCAs in seven trials (708 patients; RR 0·69, 0·54-0·87), but there was also a benefit of selective serotonin reuptake inhibitors in seven RCTs (324 patients; RR 0·74, 0·56-0·99), and serotonin and norepinephrine reuptake inhibitors in two trials (94 patients; RR 0·22, 0·08-0·59). Adverse events were not significantly more common with gut-brain neuromodulators, although rates of withdrawal due to adverse events were significantly higher. The certainty in the evidence for tricyclic antidepressants for global IBS symptoms was moderate, but it was low to very low for all other endpoints and drug classes studied.

Some gut-brain neuromodulators are efficacious in reducing global symptoms and abdominal pain in IBS. The findings support guidelines that recommend use of tricyclic antidepressants for ongoing global symptoms or abdominal pain but also highlight a potential for SSRIs to be modestly effective for abdominal pain. More data for SNRIs, azapirones, and tetracyclic antidepressants in IBS are required.

None.

Thrombopoietin receptor agonists-romiplostim, eltrombopag and avatrombopag-are commonly used as second-line treatments for immune thrombocytopenia (ITP).

A Markov model was developed to estimate the cost effectiveness of the three TPO-RAs in adults with insufficient response to previous treatment from the perspective of the UK National Health Service (NHS). The model considered the effects of bleeding events, concomitant ITP medications, rescue therapies and treatment related adverse events over a lifetime horizon. Model inputs for effectiveness were based on a network meta-analysis and other published literature on ITP management. Other model inputs included costs (e.g., drug acquisition and administration) and healthcare resource utilisation.

Avatrombopag was associated with higher quality-adjusted life-years (QALYs) (10.979) than romiplostim (10.628) and eltrombopag (10.085), producing incremental QALYs of -0.351 and -0.894, respectively. Avatrombopag was associated with lower total costs (GBP £319,334) compared with romiplostim (GBP 406,361 [cost saving of GBP 87,027]) and higher total costs compared with eltrombopag (GBP 313,987 [incremental cost of GBP 5347]). Avatrombopag therefore dominated romiplostim (more effective and less expensive) and was cost-effective versus eltrombopag (incremental cost-effectiveness ratio of GBP 5982 per QALY).

Avatrombopag is a cost-effective treatment compared with romiplostim and eltrombopag for the second-line treatment of adults with ITP from the perspective of the UK NHS.

To compare clinical outcomes in atrophic (AM) and non-atrophic (NAM) mandibles of edentulous patients rehabilitated with mandibular removable complete dentures (CD) or implant mandibular overdentures (IMO).

Non-randomized clinical studies were searched in 8 databases. Articles were assessed by the risk of bias in non-randomized studies of interventions. Datasets for CDs comparing AM and NAM were plotted [masticatory function, maximum occlusal biting force (MOBF), oral health-related quality of life (OHRQoL)]. Residual ridge (AM and NAM) data (masticatory function, OHRQoL, implant survival, marginal bone loss, and maintenance events) in IMO were also combined.

23 studies were included. Only 1 was classified as low risk of bias. Superior masticatory performance was observed in the NAM group rehabilitated with CD (P <.001). NAM group rehabilitated with CD exhibited increased MOBF (P <.05). Once patients were treated with IMO, improvements were observed in swallowing threshold (number of cycles and time) in the NAM group (P <.05). Comparable results of OHRQoL were noted for both groups (AM and NAM) and rehabilitations (CD and IMO). Similar peri-implant outcomes were displayed for IMO rehabilitation in AM and NAM patients. Most common event for IMO wearers (AM and NAM) was replacement of retention insert.

AM patients presented suboptimum masticatory function whether using CD or IMO. CD wearers with AM also had a reduced MOBF compared with NAM patients.

Clinicians should carefully monitor residual ridge resorption to guide treatment planning and prognosis, particularly in cases of AMs. Our findings indicate that AMs may negatively impact the clinical performance of both CD and IMO rehabilitations.

Current guidelines to treat atopic dermatitis (AD) overlook disease heterogeneity, limiting personalized care. This study assessed NuGel, a topical GPCR19 agonist, for efficacy, safety, and predictive baseline biomarkers in AD patients.

In a multicenter, double-blind, randomized, placebo-controlled Phase 2a trial (August 2020-September 2021, five hospitals, 80 participants), patients received placebo, 0.3% NuGel, or 0.5% NuGel twice daily for four weeks.

NuGel (0.3% [Nu0.3] and 0.5% [Nu0.5]) was well-tolerated, with no adverse drug reactions or serious adverse events. Nu0.3 showed a significant decrease in EASI score from baseline (-12.2%, [-30.3%, 5.9%], p = 0.04). Treatment with Nu0.5 resulted in a numerically decreased EASI score (-11.9%, [-34.9%, 11.1%], p > 0.05), which is comparable with placebo group (-2.9%, [-21.5%, 15.6%], p > 0.05). No significant difference was observed between groups (p>0.05). Plasma proteomic analysis identified biomarkers associated with blood coagulation, complement activation, and cell adhesion as predictors of response to Nu0.5. Patients with baseline profiles characterized by K2C5high, ENTP6low, or CRKlow demonstrated significant clinical improvement when treated with Nu0.5 compared to the placebo group. Among these, the CRKlow subgroup, comprising 54.3% of the biomarker analysis set, showed a ΔEASI of -61.3% [-99.9, -22.8; p = 0.003] and a ΔIGA of -35.2% [-58.2, -12.1; p = 0.004] compared to the placebo group. The biomarker signature demonstrated high predictive accuracy (AUC = 0.92, p = 0.002). Logistic regression analysis revealed that the threshold of predicted probability derived from the baseline plasma level of K2C5 and ENTP6 successfully stratified 100% of participants who responded to Nu0.5 (ΔEASI from baseline ≤ -50%), whereas none (0%) in the placebo group responded (p = 0.035).

Baseline biomarkers, such as K2C5, ENTP6, and CRK, may serve as predictors of clinical improvement in AD patients treated with Nu0.5, highlighting the potential for personalized treatment strategies. Further research is required to validate these findings in larger patient cohorts.

https://clinicaltrials.gov/, identifier NCT04530643.

Limited data exist on the association of glucagon-like peptide 1 receptor agonists (GLP-1RAs) with the risk of venous thromboembolism. This meta-analysis aimed to investigate the association between GLP-1RAs and the risk of venous thromboembolism including deep vein thrombosis (DVT) and pulmonary embolism.

A systematic search of PubMed, Web of Science, EMBASE, and Cochrane library was conducted from inception until July 3, 2024, to identify randomized controlled trials comparing GLP-1RAs with placebo or other anti-iabetic drugs, with reported data on DVT and pulmonary embolism. The primary outcome was venous thromboembolism, and secondary outcomes included DVT and pulmonary embolism. Pooled odds ratios (ORs) were calculated using fixed-effects models with Mantel-Haenszel method and treatment arm continuity correction for zero-event trials. A total of 39 randomized controlled trials involving 70 499 participants were included. A nonsignificant upward trend in the risk of venous thromboembolism was observed among participants using GLP-1RAs (OR, 1.19 [95% CI, 0.94-1.50]). GLP-1RAs were significantly associated with an increased risk of DVT (OR, 1.64 [95% CI, 1.14-2.36]); risk difference 25 (5-52) more events per 10 000 person-years). Subgroup analyses revealed that increased risk of DVT was particularly prominent in randomized controlled trials with treatment duration >1.5 years (OR, 2.32 [95% CI, 1.49-3.60]) and in cardiovascular outcome trials (OR, 2.18 [95% CI, 1.36-3.49]). No significant association was observed between GLP-1RAs and risk of pulmonary embolism.

GLP-1RAs might increase the risk of DVT, especially for long-term use of GLP-1RAs. Clinicians should be aware of this potential risk when prescribing GLP-1RAs.

This review aimed to evaluate the effects of bisphosphonates (BP) and denosumab on dental implants, including implant failure (IF), marginal bone loss (MBL), and medication-related osteonecrosis of the jaw (MRONJ).

A literature search was conducted in four databases and OpenGrey. Studies examining IF/MBL/MBRONJ associated with BP or denosumab were included. ROBINS-I was used to assess the risk of bias. Trial sequential analysis and the GRADE approach were used to examine the certainty of evidence. Statistical analyses were conducted using R version 4.3.1.

Twenty-one studies were included. BP was associated with IF only at the implant level (RR 1.74; 95% CI: 1.10-2.75) but not at the patient level (RR 1.01; 95% CI: 0.35-2.91). The analysis of two studies indicated no significant correlation between BP and MBL (MD 0.05; 95% CI: -0.12 to 0.21). BP was associated with MRONJ (RR 3.45; 95% CI: 2.56-4.65), whereas denosumab showed no significant statistical correlation with MRONJ (RR 25.98; 95% CI: 0.31-2165.63).

In patients with dental implants, the existing very low certainty level evidence suggests that BP intake may be associated with greater risks of IF and MRONJ but not with MBL, whereas it is currently unknown whether denosumab is associated with MRONJ.

BackgroundPatient decision aids (PtDAs) are effective interventions to help people participate in health care decisions. Although there are quality standards, PtDAs are complex interventions with variability in their attributes.PurposeTo determine and compare the effects of PtDA attributes (e.g., content elements, delivery timing, development) on primary outcomes for adults facing health care decisions.Data SourcesA systematic review of randomized controlled trials (RCTs) comparing PtDAs to usual care.Study SelectionEligible RCTs measured at least 1 primary outcome: informed values choice, knowledge, accurate risk perception, decisional conflict subscales, and undecided.Data AnalysisA network meta-analysis evaluated direct and indirect effects of PtDA attributes on primary outcomes.Data SynthesisOf 209 RCTs, 149 reported eligible outcomes. There was no difference in outcomes for PtDAs using implicit compared with explicit values clarification. Compared with PtDAs with probabilities, PtDAs without probabilities were associated with poorer patient knowledge (mean difference [MD] -3.86; 95% credible interval [CrI] -7.67, -0.03); there were no difference for other outcomes. There was no difference in outcomes when PtDAs presented information in ways that decrease cognitive demand and mixed results when PtDAs used strategies to enhance communication. Compared with PtDAs delivered in preparation for consultations, PtDAs used during consultations were associated with poorer knowledge (MD -4.34; 95% CrI -7.24, -1.43) and patients feeling more uninformed (MD 5.07; 95% CrI 1.06, 9.11). Involving patients in PtDA development was associated with greater knowledge (MD 6.56; 95% CrI 1.10, 12.03) compared with involving health care professionals alone.LimitationsThere were no direct comparisons between PtDAs with/without attributes.ConclusionsImprovements in knowledge were influenced by some PtDA content elements, using PtDA content before the consultation, and involving patients in development. There were few or no differences on other outcomes.HighlightsThis is the first known network meta-analysis conducted to determine the contributions of the different attributes of patient decision aids (PtDAs) on patient outcomes.There was no difference in outcomes when PtDAs used implicit compared with explicit values clarification.There were greater improvements in knowledge when PtDAs included information on probabilities, PtDAs were used in preparation for the consultation or development included patients on the research team.There was no difference in outcomes when PtDAs presented information in ways that decrease cognitive demand and mixed results when PtDAs used strategies to enhance communication.

Increasing evidence connects gallstone disease (GSD) to all types of cancer incidence; however, the results were inconsistent. The present study aimed to evaluate whether and to what extent these associations exist comprehensively.

We systematically searched published longitudinal studies indexed in PubMed and Embase database from dates of inception to March 31, 2020. We pooled the effect of GSD on all-cause cancer incidence. Moreover, we further employed stratified analysis concerning sex, geographic background, surgery status, and follow-up period. Trial sequential analysis (TSA) was applied to decide whether the included sample size was sufficient for evaluating these associations.

Fifty-one studies incorporating over 13 million participants were eligible for analysis in this study. GSD pose an increased risk of all-cause cancer risk (pooled RR = 1.43; 95% CI: 1.33-1.54) compared with the healthy controls, especially hematologic malignancy (pooled RR = 1.14; 95% CI: 1.05-1.25), gastrointestinal cancers (pooled RR = 1.28; 95% CI: 1.15-1.41), liver, pancreas, and biliary tract cancer (pooled RR = 1.84; 95% CI: 1.62-2.10), and kidney cancer (pooled RR = 1.19; 95% CI: 1.03-1.37). These associations are not markedly changed after stratification by different subgroups. Moreover, the TSA confirmed the sample size was sufficient to draw these conclusive conclusions.

The present meta-analysis with sufficient evidence indicates GSD increases the risk for all causes of cancer incidence. The evidence may warrant GSD patients to perform screening and prophylactic treatment for the prevention of these complications. The indication for cholecystectomy should be determined through a comprehensive evaluation of the patient's clinical presentation, with a thorough assessment of the potential therapeutic benefits and surgical risks.

Naturally derived products have become popular as a mosquito repellent in addition to mosquito nets and chemical repellents. Coconut-derived fatty acids have demonstrated repellent properties against various blood-feeding arthropods, including mosquitoes. Daily use moisturizers and body soaps containing coconut have displayed some repellent effect against mosquitoes. However, no studies have been conducted on coconut oil specifically, and the effects of pure coconut oil still remain unknown in the western Kenya region.

In this study, we investigated the effect of coconut oil on decreasing mosquito bites in a laboratory and field setting. Using Anopheles stephensi mosquitoes, the laboratory experiment compared coconut oil treated and non-treated membranes on a Hemotek blood feeding device. In the cross-sectional study in western Kenya, we investigated bite counts among 490 children, 5 years and under. Descriptive analysis, simple, multiple and mixed regression models were employed. The outcome was the number of mosquito bite marks, the primary explanatory variable was skin cream types, in addition to demographic, environmental, behavioral and socio-economic variables.

Coconut oil significantly reduced mosquito blood feeding, with a pooled Mantel-Haenszel odds ratio of 0.06, a Mantel-Haenszel chi-square statistic of 79.82 (p = 0.01), and an average blood-feeding rate of 1% compared to 31% in the control group. The mixed model identified significant factors influencing mosquito bite counts while accounting for village-level random effects. Coconut oil users experienced 15% reduction in bites (p = 0.01) compared to synthetic creams users. High and medium cream application frequencies reduced bites by 57% (p < 0.001) and 17% (p = 0.007), respectively. Late cream application and late net entry significantly increased bite counts by 41% (p < 0.001) and 53% (p < 0.001), respectively. In addition, higher temperatures from the preceding 2 weeks in the region was associated with a 26% (p = 0.003) increase in bite counts.

These findings underscore the protective impact of cream application and timing and net use timing, as well as environmental temperature influences on bite outcomes. Particularly, the effect of coconut oil in decreasing mosquito bites and its potential as an alternative repellent has been observed in both laboratory and field settings.

Around 40% of patients diagnosed with Primary Biliary Cholangitis (PBC) experience a suboptimal biochemical response to ursodeoxycholic acid (UDCA).

We aimed to compare fibrates and obeticholic acid (OCA) as add-on second-line therapy and evaluate whether these drugs hold superiority over each other.

We systematically searched Embase, MEDLINE, and Cochrane CENTRAL for studies comparing fibrates and OCA published by May 6, 2024. A pooled analysis was conducted to evaluate changes in liver biochemistry and response rates based on validated criteria. Data were expressed as mean difference (MD) for continuous outcomes and as Odds Ratio (OR) when binary.

We included 883 patients from 4 studies, 468 (53.0%) under UDCA + OCA. Follow-up time ranged from 6 to 12 months. Patients treated with fibrates have similar mean bilirubin post-intervention values (MD 0.11 × upper limit of normal [ULN]; 95% CI - 0.26 to 0.49) compared to OCA. However, fibrates demonstrated superiority over OCA for percentual reduction in ALP compared to baseline (MD 20.13%; 95% CI 11.84-28.41), ALP post-intervention values (MD - 0.59 xULN; 95% CI - 1.02 to - 0.15), and rate of ALP normalization (OR 32.34; 95% CI 14.54-71.92). Patients treated with fibrates also more frequently met Barcelona (OR 4.28; 95% CI 2.26-8.11), POISE (OR 5.48; 95% CI 2.70-11.13), and Paris II (OR 5.88; 95% CI 3.96-8.74) response criteria.

In patients with PBC and an incomplete response to UDCA, fibrates seem to be associated with greater ALP reduction and achievement of response criteria compared to OCA.

To study the impact of lack of blinding of outcome assessors on estimated treatment effects of randomized clinical trials.

Meta-epidemiological study. We included randomized trials with binary or measurement scale outcomes that (1) allocated patients to subtrials with and without blinded outcome assessment, or (2) had both blinded and non-blinded assessments of the same outcome. We identified trials from previous meta-epidemiological studies and searched six databases from 2013 to 2024. We calculated a ratio of odds ratios (ROR) for each trial. A ROR < 1 indicated a more favorable effect estimate by the non-blinded assessor. We pooled RORs using random effects meta-analysis and conducted meta-regression, subgroup, and sensitivity analyses.

We included 66 trials (9451 patients) across 18 clinical specialties. The pooled RORs in 43 trials (7055 patients) was 0.71 (0.55-0.92). Thirty of the 43 trials assessed highly subjective outcomes. Meta-regression showed no statistically significant association between ROR and scores for outcome subjectivity (P = .53), vulnerability (P = .91), and involvement (P = .99). Heterogeneity was partly explained by a larger impact in non-drug trials, ROR 0.62 (0.46-0.84), and industry-funded trials, ROR 0.57 (0.37-0.88). Sensitivity analyses, including imputed data for 23 trials (2396 patients randomized), did not modify the observed impact importantly.

We provide empirical evidence of considerable bias in effect estimates of randomized trials with non-blinded assessors of subjective binary and measurement scale outcomes. Non-blinded assessors exaggerated effect estimates, expressed as odds ratios, by 29% (8%-45%) on average. This strongly supports blinding outcome assessors of subjective outcomes.

In a randomized clinical trial, the person evaluating the results (assessor) may be either unaware of the intervention received by participants (blinded assessor) or aware of it (non-blinded assessor). Knowing which treatment a patient received can influence the assessor's evaluation of the effect; for example, if an assessor has high expectations for a new experimental intervention, they may rate a patient's improvement more favorably in the group that received the intervention compared to the group that did not. We call this observer bias. In this study, we compared the results obtained from blinded assessors to those from non-blinded assessors within the same trials to estimate the impact of observer bias in randomized trials. We found that non-blinded assessors exaggerated the experimental intervention effect by approximately 29%, on average, compared to blinded assessors. Our results indicate that when an evaluation of a patient in a randomized trial requires judgment, there is potential for substantial bias if assessors are not blinded. To ensure more reliable results, randomized clinical trials should blind assessors whenever possible.

The potential of Klebsiella pneumoniae (K. pneumoniae) to acquire and spread carbapenem-resistant genes is the most concerning characteristic of the bacteria. In hospitals and other healthcare settings, multidrug-resistant K. pneumoniae can be prevalent and cause severe infections, posing significant challenges to patient management. Studying genetic variants and drug-resistant mutations in pathogenic bacteria of public health importance is essential. Therefore, this study aimed to assess the overall prevalence of carbapenemase-encoding genes in K. pneumoniae across Africa.

All studies published between January 2010, and December 2023, were retrieved from the electronic databases PubMed, Science Direct, and Scopus, as well as through the Google Scholar search engine. This systematic review and meta-analysis adhered strictly to the PRISMA guidelines. Data analysis was performed using STATA version 17. The quality of the included studies was critically evaluated using the "Joanna Briggs Institute" criteria. To evaluate heterogeneity among the studies, inverse variance (I2) tests were utilized. Subgroup analysis was conducted when heterogeneity exists among studies. To assess publication bias, we used a funnel plot and Egger's regression test. A random effects model was used to calculate the weighted pooled prevalence of genetic variants associated with carbapenem resistance in K. pneumoniae.

A total of 49 potential studies were included in this systematic review and meta-analysis, encompassing 8,021 K. pneumoniae isolates. Among these isolates, 2,254 (28.1%) carbapenems-resistance-conferring genes were identified. The overall pooled prevalence of carbapenemase-encoding genes in K. pneumoniae isolated from clinical specimens across Africa was found to be 34.0% (95% CI: 26.01-41.98%). Furthermore, the pooled prevalence of the carbapenemase genes blaOXA-48 and blaNDM-1 was 16.96% (95% CI: 12.17-21.76%) and 15.08% (95% CI: 9.79-20.37%), respectively. The pooled prevalence of carbapenemase genes in K. pneumoniae isolates from clinical samples across Africa increased over time, reported as 20.4%(-0.7-41.4%) for 2010-2015, 34.5% (20.2-48.8%) for 2016-2020, and 35.2% (24.8-45.5%) for 2021-2023, with heterogeneity (I2) values of 36.5%, 96.7%, and 99.3%, respectively.

The emergence and spread of carbapenemase-encoding genes in K. pneumoniae pose a major threat to public health. Knowledge on the genetic mechanisms of carbapenem resistance is crucial for developing effective strategies to combat these multidrug-resistant infections and reduce their impact on healthcare systems. The carbapenemase genes blaOXA-48 and blaNDM-1 were the most prevalent and showed an increasing trend over time.

Glucagon-like peptide-1 receptor agonists are known to delay gastric emptying; however, the association between glucagon-like peptide-1 receptor agonist use and peri-operative pulmonary aspiration risk is not known. This systematic review and meta-analysis aimed to summarise the evidence on whether glucagon-like peptide-1 receptor agonist exposure is associated with pulmonary aspiration or increased residual gastric content in fasted patients undergoing procedures requiring anaesthesia or sedation.

We searched six databases for studies assessing peri-operative pulmonary aspiration or residual gastric contents in fasted patients or volunteers who were using any form of glucagon-like peptide-1 receptor agonist. Pooled odds ratios were estimated for each outcome using random effects meta-analysis. Certainty of evidence for each outcome was assessed using the GRADE framework.

Of 9010 screened studies, 28 observational studies were included. In a meta-analysis of nine studies involving 304,060 patients and 481 cases of pulmonary aspiration, glucagon-like peptide-1 receptor agonist exposure was not associated with pulmonary aspiration (OR 1.04, 95%CI 0.87-1.25, low certainty of evidence). In a meta-analysis of 18 studies involving 165,522 patients and 3831 cases of residual gastric contents, glucagon-like peptide-1 receptor agonist exposure was associated with an increased risk of residual gastric contents despite appropriate fasting (odds ratio 5.96, 95%CI 3.96-8.98, low certainty of evidence). In a meta-analysis of five studies involving 1706 patients and 208 cases of residual gastric contents, withholding at least one dose of glucagon-like peptide-1 receptor agonist before a procedure was associated with lower odds of residual gastric contents (odds ratio 0.51, 95%CI 0.33-0.81, very low certainty of evidence).

Patients using glucagon-like peptide-1 receptor agonists are at increased risk of presenting for anaesthesia with residual gastric contents, though the available evidence does not indicate that this translates to an increased risk of pulmonary aspiration.

Antimicrobial resistance (AMR) is a growing global health threat. Acinetobacter baumannii (A. baumannii) emerged as one of the most concerning critical priority pathogens due to its ability to develop resistance to multiple antimicrobial agents. In Ethiopia, the public health impact of AMR is increasingly significant, with A. baumannii responsible for a variety of infections. Although A. baumannii causes a range of infections in Ethiopian patients, the drug resistance status of the clinical isolates has not been thoroughly assessed. Therefore, this systematic review and meta-analysis aimed to determine the country-wide AMR of A. baumannii.

This systematic review and meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We conducted a search of articles on PubMed, Web of Science, Science Direct, Scopes electronic databases, Google Scholar search engine, and institutional repositories/libraries for studies published between 2015 and 2024. Eligible studies on A. baumannii-related infections and AMR in Ethiopia were assessed for quality using the Joanna Briggs Institute (JBI) criteria. Data on study characteristics were extracted, and statistical analyses, including heterogeneity (Invers of variance), publication bias (Eggers test), and subgroup analyses, were performed using STATA 17.0. A random effect model was used to compute the pooled prevalence of AMR.

This systematic review and meta-analysis of 26 Ethiopian studies (26,539 participants) found an A. baumannii prevalence of 3.99% (95% CI: 3.01-4.98%) and 9.13% of all bacterial infections (95% CI: 6.73-11.54%). The most common infections were surgical site infections, urinary tract infections, pneumonia, and sepsis. Pooled resistance to antibiotics varied, with amikacin showing the lowest resistance (20.27%) (95% CI: 11.51-29.03) and cefotaxime the highest (83.18) (95% CI: 71.87-94.48). A pooled multi-drug resistant (MDR) A. baumannii was found in 88.22% (95% CI: 82.28-94.15) of isolates, with regional and infection-type variations, particularly in higher prevalence in Oromia and Amhara regions and sepsis cases.

This systematic review underscores the alarming rise of antimicrobial resistance in A. baumannii, particularly against carbapenems. The findings highlight a high prevalence of MDR A. baumannii and widespread extended-spectrum beta-lactamase production, with notable regional variations in resistance patterns. These high resistance rates reinforce A. baumannii as a critical global health threat, necessitating urgent interventions such as enhanced antimicrobial stewardship programs, improved infection control measures, and the development of alternative treatment strategies. Healthcare professionals, policymakers, and researchers must collaborate to mitigate the clinical and public health impact of this pathogen.

This systematic review and meta-analysis was registered on PROSPERO (Registration ID: CRD42024623927).

Non-suicidal self-injury (NSSI) is a common and serious injury behavior in children and adolescents, however, its treatment remains controversial. Here, using network meta-analysis (NMA), we compared and ranked all available therapeutic treatment interventions to explore the best treatment strategy for NSSI in children and adolescents.

We searched PubMed, Embase, the Cochrane Library and PsycINFO for randomized controlled trials used to reduce the frequency of NSSI in children and adolescents from database inception until Jan. 11, 2025. Primary outcomes were efficacy and acceptability. We estimated summary odds ratios (ORs) with credible intervals (CIs) in random effects models.

We included 28 trials comprising 6496 participants. Dialectical behavior therapy (DBT) was better than other interventions. In subgroup analysis, pharmacotherapy and psychotherapy significantly aggravated the frequency of NSSI in depression (OR = 1.53; 95% CI: 1.10 to 2.14); however, these interventions significantly reduced NSSI in patients with self-harm (OR = 0.53; 95% CI: 0.30 to 0.96). We also found that NSSI was significantly increased in the first 3 months when using SSRIs in treatment but was significantly reduced after 3 months.

Psychotherapy seems to be a better choice than pharmacotherapy, especially DBT. DBT was associated with a better reduction in the frequency of NSSI than treatment as usual, with high confidence of evidence. NSSI is frequently used to combat depression symptoms, suggesting that clinicians should pay greater attention to depression symptoms to reduce NSSI, especially in the first 3 months of treatment with SSRIs.

Ventricular arrhythmias (VA), including ventricular tachycardia and fibrillation, are critical cardiac conditions that are often managed by catheter ablation among those unresponsive to pharmacologic therapy. The choice of anesthesia and sedation regimens for VA ablations may impact arrhythmia inducibility and hemodynamic stability, which can affect procedural success and complication rates. This systematic review and meta-analysis aimed to compare the efficacy and safety of sedation versus general anesthesia (GA) among patients undergoing VA ablation. The review was prospectively registered on PROSPERO (CRD42023441553). Database searches were conducted across five major databases from inception to March 9, 2024 to identify randomized trials or observational studies including adult patients undergoing ablations for VA. Screening and data extraction were completed in duplicate. Risk-of-bias assessments were conducted using ROBINS-I as all included studies were observational, and the quality of evidence was evaluated using the GRADE framework. Six observational studies (N = 16,435) were included. No significant differences were found between sedation and GA for total procedure time (MD: -14.16 minutes; 95%CI: -38.61 to 10.29 minutes), arrhythmia non-inducibility (RR: 0.73; 95% CI: 0.33-1.58), acute ablation success (RR: 1.06; 95% CI: 0.65-1.71), or procedural complications (RR: 0.72; 95% CI: 0.28-1.85). However, sedation was associated with significantly lower intraprocedural hemodynamic instability (RR: 0.28; 95% CI: 0.12-0.70). These findings indicate that while sedation and GA have comparable outcomes, sedation may be associated with less hemodynamic instability during VA ablation. However, more high-quality studies are needed to confirm these results.

Antimicrobial resistance among Enterobacteriaceae poses a significant global threat, particularly in developing countries. Colistin, a critical last-resort treatment for infections caused by carbapenem-resistant and multidrug-resistant strains, is increasingly facing resistance due to inappropriate use of colistin and the spread of plasmid-mediated resistance genes. Despite the significance of this issue, comprehensive and updated data on colistin resistance in Africa is lacking. Thus, the current study was aimed to determine the pooled prevalence of colistin-resistant Enterobacteriaceae in Africa.

A systematic search was conducted across PubMed, Scopus, ScienceDirect, and Google Scholar to identify relevant studies. Forty-one studies reporting on the prevalence of colistin resistance in Enterobacteriaceae isolates from clinical specimens in Africa were included in the analysis. Stata 17 software was used to calculate the pooled prevalence of colistin resistance, employing a random-effects model to determine the event rate of resistance. Heterogeneity across studies was assessed using the I2 statistic, and publication bias was evaluated using Egger's test. Subgroup analyses were performed to address any identified heterogeneity.

This systematic review analyzed the colistin resistance profile of 9,636 Enterobacteriaceae isolates. The overall pooled prevalence of colistin resistance was 26.74% (95% CI: 16.68-36.80). Subgroup analysis by country revealed significant variability in resistance rates, ranging from 0.5% in Djibouti to 50.95% in South Africa. Species-specific prevalence of colistin resistance was as follows: K. pneumoniae 28.8% (95% CI: 16.64%-41.05%), E. coli 24.5% (95% CI: 11.68%-37.3%), Proteus spp. 50.0% (95% CI: 6.0%-106.03%), and Enterobacter spp. 1.22% (95% CI: -0.5%-3.03%). Analysis based on AST methods revealed significant differences in colistin resistance rates (p = 0.001). The resistance rates varied between 12.60% for the disk diffusion method and 28.0% for the broth microdilution method. Additionally, a subgroup analysis of clinical specimens showed significant variation (p < 0.001) in colistin resistance. Stool specimen isolates had the highest resistance rate at 42.0%, while blood specimen isolates had a much lower resistance rate of 3.58%.

Colistin resistance in Enterobacteriaceae is notably high in Africa, with significant variation across countries. This underscores the urgent need for effective antimicrobial stewardship, improved surveillance, and the development of new antibiotics.

The optimal long-term antithrombotic strategy in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) remains uncertain. Individual randomized controlled trials (RCTs) had variations in their reported results and were not powered for effectiveness outcomes.

This study aimed to pool the results of RCTs comparing the effectiveness and safety of oral anticoagulation (OAC) monotherapy vs OAC plus single antiplatelet therapy (SAPT) in patients with AF and stable CAD.

We systematically searched PubMed, Embase, and ClinicalTrials.gov until September 09, 2024. The primary effectiveness outcome was a composite of myocardial infarction, ischemic stroke, systemic embolism, or death. The primary safety outcome was major bleeding. We obtained unpublished results from principal investigators of the included RCTs, as needed, to calculate pooled HRs and 95% CIs and to perform prespecified subgroup analyses.

Among 690 screened records, 4 RCTs with 4,092 randomized patients were included (2 using edoxaban, 1 using rivaroxaban, and 1 using any oral anticoagulant; mean age 73.9 years, 20.1% women). The median follow-up durations ranged from 12 to 30 months (overall estimated weighted mean follow-up of 21.9 months). There were no statistically significant differences between OAC monotherapy vs OAC plus SAPT in the primary effectiveness outcome (7.3% vs 8.2%; HR: 0.90; 95% CI: 0.72-1.12), myocardial infarction (1.0% vs 0.7%; HR: 1.51; 95% CI: 0.75-3.04), ischemic stroke (1.9% vs 2.1%; HR: 0.89; 95% CI: 0.57-1.37), all-cause death (4.2% vs 5.3%; HR: 0.94; 95% CI: 0.49-1.80), or cardiovascular death (2.4% vs 3.0%; HR: 0.79; 95% CI: 0.54-1.15). OAC monotherapy was associated with a lower risk of major bleeding than OAC plus SAPT (3.3% vs 5.7%; HR: 0.59; 95% CI: 0.44-0.79). Subgroup analyses did not show significant interactions for effectiveness but suggested that the magnitude of bleeding reduction may be greater among men (Pinteraction = 0.03) and among patients with diabetes mellitus (Pinteraction = 0.04).

In patients with AF and stable CAD, OAC monotherapy, compared with OAC plus SAPT, was not associated with a statistically significant increased risk of ischemic events but resulted in a significantly reduced risk of bleeding.

The Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) are established classification systems used to evaluate atrophic gastritis and intestinal metaplasia, respectively.

We evaluated the association of OLGA and OLGIM scores and the risk of gastric cancer (GC) in only prospective cohort studies.

Systematic review and meta-analysis.

We systematically searched four databases for prospective cohorts that evaluated the use of OLGA and OLGIM staging systems in predicting the risk of GC. We primarily compared OLGA/OLGIM III-IV versus OLGA/OLGIM 0-II categories and GC events. Pooled risk ratios (RR) and absolute risk differences with their 95% confidence intervals (CIs) were calculated.

Eight studies were included (n = 12,526). The mean age of the patients ranged from 48.2 to 64.9 years. OLGA III-IV and OLGIM III-IV were associated with the development of GC in comparison to their 0-II categories (RR 32.31, 95% CI 9.14-114.21 and RR 12.38, 95% CI 5.75-26.65, respectively). OLGA III-IV and OLGIM III-IV were associated with an increase in the absolute risk of GC of 4% and 5%, respectively. The risk remained significant if we only included countries with high incidence of GC, and was greater if we excluded one study that included mostly patients with autoimmune gastritis. OLGA II and OLGIM II were associated with higher risk of high-grade dysplasia (HGD) and GC in comparison with OLGA 0-I and OLGIM 0-I, respectively.

Higher stages in OLGA and OLGIM systems are associated with a significantly increased risk of developing HGD and GC, validating these scoring systems for the assessment of GC risk and the design of endoscopic surveillance programs.

CRD42024565771.

The use of transcatheter aortic valve implantation (TAVI) for severe aortic stenosis is expanding to patients across the entire spectrum of surgical risk. We performed a meta-analysis and compared TAVI with surgical aortic valve replacement (SAVR) in trials that enrolled lower-risk patients.

We conducted a meta-analysis of randomized controlled trials and compared safety and efficacy outcomes between TAVI and SAVR among lower-risk patients (mean and/or median Society of Thoracic Surgeons [STS] score < 4). Point-estimate meta-analysis and reconstructed individual patient data survival analysis were conducted. Primary outcomes included all-cause mortality, stroke, and a composite of all-cause mortality or disabling stroke (PROSPERO, CRD42024541837).

The analysis included 6 randomized controlled trials, totaling 2668 TAVI and 2573 SAVR patients, with a mean follow-up time of 3.02 years. TAVI was associated with lower risk of all-cause mortality (risk ratio, 0.68; 95% confidence interval, 0.52-0.88) and a composite of all-cause mortality or disabling stroke (risk ratio, 0.69; 95% confidence interval, 0.55-0.86) without a significant difference in stroke up to 2 years. Longer-term point-estimate analysis showed no difference. In reconstructed individual patient data, TAVI was associated with a lower risk of all-cause mortality, driven by an early advantage. Restricted mean survival time differences for primary outcomes were < 2.5 months and ≤ 1 month for all-cause mortality. TAVI was associated with a lower risk of bleeding, kidney injury, and atrial fibrillation, but a higher risk of pacemaker implantation and moderate to severe aortic regurgitation.

In patients at lower surgical risk, TAVI was associated with improved short-term mortality. More data from long-term studies are needed.

The effectiveness of intra-articular platelet-rich plasma (IA-PRP) injections for managing pain in knee osteoarthritis (KOA) remains inconsistent. Therefore, this study aimed to systematically review randomized controlled trials (RCTs) assessing the efficacy of IA-PRP.

A total of 21 studies meeting the inclusion criteria were selected from various scientific databases, all of which compared PRP to either a placebo or an active comparator, such as corticosteroids (CS), in the treatment of KOA. Weighted mean differences (WMDs) for the Visual Analogue Scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Knee Injury and Osteoarthritis Outcome Score (KOOS), along with their 95 % confidence intervals (CIs), were calculated for each study. A subgroup analysis was conducted for the pain scores, comparing leukocyte-poor and leukocyte-rich PRP with either a placebo or CS. The evidence was synthesized using a random-effects meta-analysis.

There were 2406 participants in all included studies; 1223 were in the PRP versus placebo group and 1183 were in the PRP versus corticosteroid group. The IA-PRP showed significant improvement of VAS, and WOMAC scores compared to placebo (P < 0.00.05), except KOOS score (P > 0.05). All pain scores were highly sinficant improved with IA-PRP, compared to IA-CS (P < 0.05). Additionally, the leukocyte rich PRP was efficasious than leukocyte poor PRP (P < 0.05) improving the all pain scores at the 6-month follow-up.

PRP treatment showed better results than placebo and corticosteroids in terms of reducing pain and improving function in KOA patients. Furthermore, lecocyte rich PRP is more effective than lecocyte poor PRP [PROSPERO, CRD42024540507].

Zero-event counts are common in clinical studies, particularly when assessing rare adverse events. These occurrences can result from low event rates, short follow-up periods, and small sample sizes. When both intervention and control groups report zero events in a clinical trial, the study is referred to as a double-zero-event study, which presents methodological challenges for evidence synthesis. There has been ongoing debate about whether these studies should be excluded from evidence synthesis, as traditional two-stage meta-analysis methods may not estimate an effect size for them. Recent research suggests that these studies may still contain valuable clinical and statistical information.

This study examines the role of double-zero-event studies from the perspective of the fragility index (FI), a popular metric for assessing the robustness of clinical results. We aim to determine how including or excluding double-zero-event studies affects FI derivations in meta-analyses.

We conducted an illustrative case study to demonstrate how double-zero-event studies can impact FI derivations. Additionally, we performed a large-scale analysis of 12,184 Cochrane meta-analyses involving zero-event studies to assess the prevalence and effect of double-zero-event studies on FI calculations.

Our analysis revealed that FI derivations in 6608 (54.2%) of these meta-analyses involved double-zero-event studies. Excluding double-zero-event studies could lead to artificially inflated FI values, potentially misrepresenting the results as more robust than they are.

We advocate for retaining double-zero-event studies in meta-analyses and emphasise the importance of carefully considering their role in FI assessments. Including these studies ensures a more accurate evaluation of the robustness of clinical results in evidence synthesis.

Prison populations have been increasing worldwide. Previous studies suggest that there is a high burden of psychiatric morbidity in people in prison, but, to our knowledge, the last published meta-analysis of prevalence is more than a decade old. We aimed to describe the pooled prevalence of depression, psychosis, bipolar disorder, and schizophrenia spectrum disorders for people who are incarcerated.

In this updated systematic review and meta-analysis, we searched six databases and grey literature published from database inception until Aug 8, 2024, with no language or geographical restrictions. We included primary quantitative studies that reported the prevalence of depression and psychotic disorders in the unselected prison population, based their diagnoses on clinical examination or from interviews and by the use of validated diagnostic instruments, met standardised criteria of the ICD or the Diagnostic and Statistical Manual of Mental Disorders for the diagnoses, and provided pooled prevalences for psychosis in the previous 6 months and clinical depression in the previous 2 weeks to 1 month. We excluded studies that used selected samples or were only qualitative. We investigated bipolar and schizophrenia spectrum disorders as separate diagnostic subcategories. We synthesised studies using random-effects meta-analysis and explored heterogeneity with meta-regression and subgroup analyses. The protocol is registered with PROSPERO, CRD42022378568.

We identified 131 publications reporting the prevalence of mental illness in 58 838 people in prison in 43 countries. We estimated that the prevalence of depression was 12·8% (95% CI 11·1-14·6) and for any psychosis was 4·1% (3·6-4·7). For diagnostic subcategories, we found that the prevalence of bipolar disorder was 1·7% (1·0-2·6) and schizophrenia spectrum disorders was 3·6% (1·3-7·1). Between-study heterogeneity was substantial for these estimates (I2 69-97%) with few explanations. However, subgroup analyses revealed that people in prison in low-income and middle-income countries had higher prevalences for depression (16·7% [95% CI 13·6-20·0]) than in high-income countries (10·8% [9·0-13·0]), and that, for people with psychosis who are incarcerated, psychiatrists were less likely to diagnose (3·5% [2·8-4·3]) than were non-psychiatrists (4·7% [3·9-5·5]).

Our study indicates that the prevalence of severe mental illness in people who are incarcerated worldwide is considerable. Meeting the treatment needs of people in prison who have mental ill health remains an ongoing challenge for public mental health. More evidence on how to improve the assessment, treatment, and linkage to services on release, which will require more research-friendly prison services, is now needed.

None.

Linezolid-induced thrombocytopenia (LIT) occurs in a dose-dependent manner. There is no consensus regarding personalized dosing of linezolid in the real world. This study investigated the usefulness of personalized dosing for the potential mitigation of LIT compared with standard dosing.

A systematic review and meta-analysis were performed using 4 medical electronic databases. Inclusion criteria were original research articles published up to October 23, 2023, whereas nonoriginal articles were excluded. Eligible participants included adults who were administered linezolid. A random-effects model was used to synthesize the results.

Four studies were eligible for inclusion. There were 208 patients in the personalized dosing (intervention) group and 195 patients in the standard dosing (comparison) group. The odds ratio for the intervention was 0.648 (95% confidence interval: 0.150-2.797), although significant heterogeneity was observed (I2 = 83.3%). An ad hoc analysis was performed by excluding one study with a significant bias risk in the treatment duration. The odds ratio for the intervention in the ad hoc analysis was 0.356 (95% confidence interval: 0.179-0.708) with little heterogeneity, showing a lower incidence risk of LIT.

Personalized dosing in linezolid therapy may mitigate the risk of LIT.

Accurate classification of lymphadenopathy is essential for determining the pathological nature of lymph nodes (LNs), which plays a crucial role in treatment selection. The biopsy method is invasive and carries the risk of sampling failure, while the utilization of non-invasive approaches such as ultrasound can minimize the probability of iatrogenic injury and infection. With the advancement of artificial intelligence (AI) and machine learning, the diagnostic efficiency of LNs is further enhanced. This study evaluates the performance of ultrasound-based AI applications in the classification of benign and malignant LNs.

The literature research was conducted using the PubMed, EMBASE, and Cochrane Library databases as of June 2024. The quality of the included studies was evaluated using the QUADAS-2 tool. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated to assess the diagnostic efficacy of ultrasound-based AI in classifying benign and malignant LNs. Subgroup analyses were also conducted to identify potential sources of heterogeneity.

A total of 1,355 studies were identified and reviewed. Among these studies, 19 studies met the inclusion criteria, and 2,354 cases were included in the analysis. The pooled sensitivity, specificity, and DOR of ultrasound-based machine learning in classifying benign and malignant LNs were 0.836 (95% CI [0.805, 0.863]), 0.850 (95% CI [0.805, 0.886]), and 33.331 (95% CI [22.873, 48.57]), respectively, indicating no publication bias (p = 0.12). Subgroup analyses may suggest that the location of lymph nodes, validation methods, and type of primary tumor are the sources of heterogeneity.

AI can accurately differentiate benign from malignant LNs. Given the widespread use of ultrasonography in diagnosing malignant LNs in cancer patients, there is significant potential for integrating AI-based decision support systems into clinical practice to enhance the diagnostic accuracy.

To assess the efficacy and safety of corticosteroids for the management of pediatric sepsis and septic shock.

Ovid MEDLINE, Ovid Embase, CENTRAL, Web of Science (Core Collection) and China National Knowledge Infrastructure were systematically searched up to September 2023. Preprint servers, clinical trial registries and the reference sections of previous reviews were hand-searched.

Randomized controlled trials that enrolled pediatric sepsis, septic shock or systemic inflammatory response syndrome patients, compared the use of corticosteroid regimens against standard sepsis care and reported eligible outcomes were included. Title/abstract and full-text screening were conducted in-duplicate.

Eligible articles were extracted using a standardized form in-duplicate. Outcomes extracted include mortality incidence, hospital and pediatric intensive care unit length of stay, duration of shock, incidence of adverse events and serious adverse events and incidence of corticosteroid-related adverse events. The risk of bias was assessed using the Revised Cochrane Risk of Bias Tool for Assessing Randomized Trials.

Random-effects meta-analyses were conducted, and the quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach. Sixteen randomized controlled trials (N = 973) were included. Corticosteroid use may be associated with reduced mortality risks (risk ratio: 0.65, 95% CI: 0.50-0.85), shorter length of hospital stay (MD: -3.76 days, 95% CI: -6.66 to -0.86), and shorter pediatric intensive care unit length of stay (MD -2.34 days, 95% CI: -3.14 to -1.53 days). Corticosteroid use may be associated with gastrointestinal bleeding but not a higher risk of secondary infection. No studies reported on serious adverse events. All findings were based on low to very low quality of evidence.

While corticosteroids show promise for managing pediatric sepsis and septic shock, the question of how to select the best candidate and the most optimal regimen remains unanswered. Future trials need to focus on assessing corticosteroid-related adverse events and stratifying patient inclusion by sepsis subphenotypes.

Mental health apps are efficacious, yet they may pose risks in some. This review (CRD42024506486) examined adverse events (AEs) from mental health apps. We searched (May 2024) the Medline, PsycINFO, Web of Science, and ProQuest databases to identify clinical trials of mental health apps. The risk of bias was assessed using the Cochrane Risk of Bias tool. Only 55 of 171 identified clinical trials reported AEs. AEs were more likely to be reported in trials sampling schizophrenia and delivering apps with symptom monitoring technology. The meta-analytic deterioration rate from 13 app conditions was 6.7% (95% CI = 4.3, 10.1, I2 = 75%). Deterioration rates did not differ between app and control groups (OR = 0.79, 95% CI = 0.62-1.01, I2 = 0%). Reporting of AEs was heterogeneous, in terms of assessments used, events recorded, and detail provided. Overall, few clinical trials of mental health apps report AEs. Those that do often provide insufficient information to properly judge risks related to app use.

The safety and efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors in hospitalized patients are unclear.

To evaluate outcomes of inpatient SGLT2 inhibitor use.

MEDLINE, Embase, Emcare, and Cochrane databases were searched through 29 May 2024.

Randomized controlled trials (RCTs) and observational cohort studies with assessment of SGLT2 inhibitor use in patients hospitalized for any reason were included.

Study characteristics and clinical outcomes were extracted.

We performed a random-effects meta-analysis analyzing RCTs and cohort studies separately. Heterogeneity was quantified with the I2 statistic. Twenty-three RCTs comprising 19,846 participants (29.5% with type 2 diabetes) with comparison of SGLT2 inhibitors with placebo or active comparator were included. Ketoacidosis rates were 0.210 per 100 person-years (95% CI 0.119, 0.370) for SGLT2 inhibitors and 0.140 per 100 person-years (95% CI 0.070, 0.280) for control (rate ratio 1.50 [95 CI 0.56, 4.23], P = 0.38). SGLT2 inhibitor use was associated with fewer readmissions and urgent visits (odds ratio [OR] 0.64 [95 CI 0.47, 0.86], P < 0.01) and lower mortality rates (OR 0.74 [95% CI 0.56, 0.98], P = 0.03) in heart failure trials and lower incidence of acute kidney injury (OR 0.76 [95% CI 0.60, 0.97], P = 0.03) among all RCTs. Twenty observational studies were included and did not show increased adverse events.

Ketoacidosis rates were low, likely leading to lack of power to detect significant differences.

SGLT2 inhibitor use among hospitalized patients was associated with numerically higher rates of ketoacidosis, although further studies are required.

Newer glucose-lowering drugs (GLDs) protect against cerebrovascular, neurodegenerative, and neuroinflammatory pathologies. Therefore, we performed a meta-analysis of randomized controlled trials (RCTs) comparing newer GLDs to placebo that assessed long-term cardiovascular and renal outcomes to analyze their potential to prevent late-onset seizures and epilepsy, separately and as a combined outcome. A comprehensive MEDLINE and CENTRAL databases search for DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitor RCTs, which reported adverse effects, including seizures and epilepsy on clinicaltrials.gov, yielded 413 studies. Of them, 27 studies with almost 200 000 patients (mean age 64.9 years, 65.6% males) were included. We calculated relative risk (RR) and odds ratio (OR) using the Mantel-Haenszel method and Peto's method. Patients taking newer GLDs had a 24% lower risk of late-onset seizures and epilepsy, combined, (RR: 0.76, 95% CI: 0.62-0.95) and 22% lower risk of late-onset seizures only (RR = 0.78; 95% CI = 0.60-1.00), compared to patients on placebo. This seizure and epilepsy prevention benefit was only noted among patients taking GLP-1 receptor agonists. Stroke incidence was comparable between newer GLDs and placebo group. GLP-1 receptor agonists like Semaglutide significantly reduce late-onset seizures and epilepsy, and their anti-epileptogenic potential in older adults needs further exploration. PLAIN LANGUAGE SUMMARY: Our analysis 27 clinical trials and nearly 200 000 patients evaluated the potential of newer glucose-lowering drugs (GLDs) to prevent late-onset seizures and epilepsy in older adults. The study found that newer GLDs, especially GLP-1 receptor agonists like Semaglutide, reduced the combined risk of seizures and epilepsy by 24% compared to placebo. These findings suggest that newer GLDs may offer prevention against the development of seizures and epilepsy in older adults. However, further research is needed to confirm their anti-epileptogenic effects.

Dysphagia or swallowing dysfunction is common in patients with acute or critical illness, and diverse methods of dysphagia rehabilitation are provided worldwide. We aimed to examine the efficacy of rehabilitation to treat dysphagia in patients with acute or critical illness. We searched PubMed, ICHUSHI, and Cochrane Central Register of Controlled Trials databases from inception to November 22, 2023 for relevant randomized controlled trials. We focused on dysphagic patients with acute or critical illness who were not orotracheally intubated. Our target intervention included conventional rehabilitation and nerve stimulation/neuromodulation techniques as dysphagia rehabilitation. Comparators were conventional or standard care or no dysphagia interventions. Primary outcomes included mortality, incidence of pneumonia during the study period, and health-related quality of life (HRQoL) scores within 90 days of hospital discharge. We pooled the data using a random-effects model, and classified the certainty of evidence based on the Grading of Recommendations, Assessment, Development, and Evaluation system. Nineteen randomized controlled trials involving 1,096 participants were included. Dysphagia rehabilitation was associated with a reduced incidence of pneumonia (risk ratio [RR], 0.66; 95% confidence interval [CI], 0.54-0.81; moderate certainty), but not with reduced mortality (RR, 0.92; 95% CI, 0.61-1.39; very low certainty) or improved HRQoL scores (mean difference, -0.20; 95% CI, -20.34 to 19.94; very low certainty). Based on the available moderate- or very low- quality evidence, while dysphagia rehabilitation had no impact on mortality or HRQoL, they might reduce the incidence of pneumonia in dysphagic patients with acute or critical illness.

Given the complex role of immunity in dengue severity, we aimed to review the clinical course of dengue infection in immunocompromised patients.

We conducted a systematic review of studies reporting outcomes among immunocompromised patients with laboratory-confirmed dengue infection. Meta-analysis using the Mantel-Haenszel method (fixed effects) was performed for studies with control groups. We registered the study with PROSPERO (No. CRD42021258930).

We included 115 studies. Among these, 30 studies compared immunocompromised (cases) and nonimmunocompromised (control) patients, focusing mainly on children (n = 22 studies) with malnutrition (n=18). Immunocompromised patients had a higher likelihood of dengue complications (OR 1.87; 95% CI: 1.04-3.35]) but a lower likelihood of severe dengue (OR 0.83; 95% CI: 0.69-1.00]. No significant difference in mortality was observed. In the 85 studies focused solely on immunocompromised patients, severe dengue and mortality rates were 9% and 4%, respectively, mostly among adult solid organ transplant recipients and those with inflammatory diseases. Immunosuppressive treatment alterations and temporary graft dysfunction were reported.

Immunocompromised patients have an increased risk of dengue-related complications. However, definitive conclusions about the comparative severity of dengue across different immunocompromised patient groups are limited by a lack of robust data, highlighting the need for well-designed future studies.

To investigate the association of disease-modifying antirheumatic drugs (DMARDs) and risk of incident interstitial lung disease (ILD) among patients with rheumatoid arthritis (RA) using a systematic literature review and meta-analysis.

We performed a systematic literature review and meta-analysis of studies examining the association of DMARDs with incident RA-ILD. PubMed, Embase, Web of Science, and Cochrane Library were searched from inception to November 2023 for randomized controlled trials (RCTs), observational studies, and post-marketing surveillance studies that investigated adults with RA and compared DMARDs of interest with placebo, no DMARDs, or other DMARDs. The outcome was incident ILD. We summarized the literature on DMARDs and incident RA-ILD risk. Among studies with sufficient quality, we performed meta-analyses to obtain odds ratios (OR) and 95 % confidence intervals (95 %CI) using the Mantel-Haenszel method.

Among 3,612 studies, we identified a total of 40 papers that encompassed 486,465 patients with RA and 3,928 incident ILD outcomes that were included in the final systematic review and meta-analysis. Among the studies, 24 were RCTs, 4 were prospective cohort studies, 9 were retrospective cohort studies, 2 were case-control studies, and 1 was a post-marketing surveillance study. The pooled analysis from RCTs revealed no statistically significant difference in the odds of ILD development for any specific DMARD across all comparisons examined. The largest identified RCT (Oral Surveillance trial) of tofacitinib (n = 2,911) vs. tumor necrosis factor inhibitor (TNFi, n = 1,451) found no relationship with incident ILD (OR 0.94, 95 %CI 0.52 to 1.69, p = 0.828). In 7 observational studies, the use of methotrexate (MTX) yielded a pooled OR for ILD of 0.49 (95 %CI 0.32 to 0.76, p < 0.001) compared to those not using MTX. In a single observational study, tofacitinib users had an OR for ILD of 0.36 (95 %CI 0.15 to 0.87, p = 0.024) compared to TNFi users.

Observational data suggest no increased risk for any DMARD for incident RA-ILD risk, and perhaps a potential protective role of MTX and tofacitinib. However, these studies may be susceptible to bias, and no specific DMARD showed associations with incident RA-ILD in RCTs. Further well-designed prospective studies are warranted for definitive conclusions on the potential relationship between DMARDs and RA-ILD risk.

We sought to determine the prevalence of strabismus and the esotropia/exotropia ratio in Down syndrome. Wide ranges of an increased strabismus prevalence have been reported and it is unclear by how much esotropia exceeds exotropia in people with Down syndrome.

We compiled in a systematic review and meta-analysis the results of over 100 studies that report the strabismus prevalence and ratio of esotropia/exotropia in cohorts of Down syndrome. We calculated the pooled global prevalence and established the geographical distribution of the strabismus prevalence and the esotropia/exotropia ratio.

The ethnically-adjusted global prevalence of strabismus in Down syndrome is 30.2%. In subjects 15 years and older, the global prevalence is 53.2%, and the lifetime prevalence is 51.0%. In populations which normally have more esotropia than exotropia (e.g., Caucasians), Down syndrome subjects have a further increased bias towards esotropia. In populations which normally have more exotropia (e.g., West Africans, Asians and Hispanics), Down syndrome subjects have a significantly lower esotropia/exotropia ratio (3.21) than reported in Caucasians with Down syndrome (9.98).

Worldwide, about 1.81 million people with Down syndrome have strabismus: 1.42 million of them have esotropia, and 0.37 million have exotropia. Differences in the esotropia/exotropia ratio between ethnicities point to the orbital anatomy as a major contributing factor to the etiology of strabismus in Down syndrome. The narrow-set eyes (reduced orbital width) in Down syndrome favor esotropia over exotropia, especially in Caucasians, thus explaining why Down syndrome patients from different ethnicities have different prevalences of esotropia and exotropia.

Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes. We aimed to perform a comprehensive meta-analysis of all randomized, sham-controlled trials investigating RDN with first- and second-generation devices in hypertension.

We searched MEDLINE and the Cochrane Library for eligible trials. Outcomes included both efficacy (24-hour and office systolic [SBP] and diastolic blood pressure [DBP]) and safety (all-cause death, vascular complication, renal artery stenosis >70%, hypertensive crisis) of RDN. We performed a study-level, pairwise, random-effects meta-analysis of the summary data.

Ten trials comprising 2478 patients with hypertension while being either off or on treatment were included. Compared with sham, RDN reduced 24-hour and office systolic blood pressure by 4.4 mm Hg (95% CI, 2.7 to 6.1; P<0.00001) and 6.6 mm Hg (95% CI, 3.6 to 9.7; P<0.0001), respectively. The 24-hour and office diastolic blood pressure paralleled these findings (-2.6 mm Hg [95% CI, -3.6 to -1.5]; P<0.00001; -3.5 mm Hg [95% CI, -5.4 to -1.6]; P=0.0003). There was no difference in 24-hour and office systolic blood pressure reduction between trials with and without concomitant antihypertensive medication (P for interaction, 0.62 and 0.73, respectively). There was no relevant difference in vascular complications (odds ratio, 1.69 [95% CI, 0.57 to 5.0]; P=0.34), renal artery stenosis (odds ratio, 1.50 [95% CI, 0.06 to 36.97]; P=0.80), hypertensive crisis (odds ratio, 0.65 [95% CI, 0.30 to 1.38]; P=0.26), and all-cause death (odds ratio, 1.76 [95% CI, 0.34 to 9.20]; P=0.50) between RDN and sham groups. Change of renal function based on estimated glomerular filtration rate was comparable between groups (P for interaction, 0.84). There was significant heterogeneity between trials.

RDN safely reduces ambulatory and office systolic blood pressure/diastolic blood pressure versus a sham procedure in the presence and absence of antihypertensive medications.