Atrial Fibrillation (AF) and Type 2 Diabetes Mellitus (T2DM) are comorbid conditions associated with increased adverse outcomes. Recent evidence suggests that antidiabetic therapies such as sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 agonists (GLP1a) may influence the risk of AF and stroke differently. This study aims to compare the risk of new-onset AF and stroke in T2DM patients treated with SGLT2i versus GLP1a. A systematic literature review was performed on Pubmed and Embase, including studies comparing the effect of SGLT2i or GLP1a on new-onset AF and stroke incidence in T2DM patients. A random effects model was used to pool relative risk and 95% confidence intervals to assess the study outcomes. Univariate metaregression analysis was performed for selected demographics and comorbidities. Six observational studies were included in the analysis comprising 847,028 patients. Our meta-analysis found a significantly lower risk of new-onset AF in patients with T2DM treated with SGLT2i compared to those receiving GLP1a (RR = 0.76, 95% CI: 0.65 to 0.89). There was no statistically significant difference in the risk of stroke between SGLT2i and GLP1a (RR = 1.09, 95% CI = 0.98 to 1.21). Univariate meta-regression indicated male sex was a significant negative effect modifier for new-onset AF (coefficient = -0.0191, p-value = 0.0158). In conclusion, SGLT2i may reduce AF risk in T2DM patients, while GLP1a may provide a modest, nonsignificant protective effect against stroke. Further research is needed to confirm these results and guide cardiovascular risk management in patients with T2DM.

To evaluate the effects of polyphenol-containing products during pregnancy on preeclampsia-related maternal and neonatal outcomes.

Systematic review and meta-analysis.

Nine databases and one trial registry, from inception to August 11th, 2023.

Randomised controlled trials where women received polyphenolic-containing products (as standardised extracts or dietary supplements) compared to placebo or standard care.

All review stages were conducted by two independent reviewers. Random-effects meta-analysis with the Hartung-Knapp-Sidik-Jonkman method using a framework for studies with few events.

Clinical outcomes combining the core outcome set for preeclampsia and WHO's priority outcomes.

Fourteen trials investigating six candidates were included. In women with preeclampsia, the addition of epigallocatechin gallate (EGCG) to nifedipine may reduce the time needed to achieve blood pressure control (mean difference (MD) = -14.10 min, 95% CI -18.46 to -9.74) and increase the time to the next hypertensive crisis (MD = 3.10 h, 95% CI 2.35 to 3.85) compared to nifedipine alone (1 trial, 349 women; low certainty). Similarly, the addition of resveratrol to nifedipine may reduce the time needed to achieve blood pressure control (MD = -15.50 min, 95% CI -19.83 to -11.17) and increase the time to the next hypertensive crisis (MD = 2.50 h, 95% CI 2.09 to 2.91) (1 trial, 349 women; low certainty). No differences were observed for other outcomes or candidates (Salvia miltiorrhiza, Bryophyllum pinnatum , raspberry and cranberry extracts).

ECGC and resveratrol supplements have been investigated for potential effects in managing clinical signs and symptoms of preeclampsia; however, evidence on the clinical and adverse effects of polyphenols is limited and uncertain.

A systematic review and meta-analysis were conducted to evaluate the safety and effectiveness of live attenuated vaccines (LAVs) against African swine fever (ASF) in domestic pigs, focusing on three major disease outcomes: mortality, fever, and clinical signs. The findings indicated that vaccinated pigs exhibited significantly lower risks of mortality (RR = 0.30, 95 % CI: 0.24-0.39), fever (RR = 0.46, 95 % CI: 0.38-0.56), and clinical signs (RR = 0.34, 95 % CI: 0.27-0.43), compared to unvaccinated controls, corresponding to vaccine efficacies (VE) of 70 %, 54 %, and 66 %, respectively. Although this marks significant progress toward ASF control through vaccination, the presence of significant side effects in some vaccinated pigs, such as fever (RD = 0.24, 95 % CI: 0.15-0.34) and clinical reactions (RD = 0.11, 95 % CI: 0.05-0.18) indicates that current vaccine candidates require further refinement to achieve the level of safety and protection needed for field application. Subgroup analysis revealed that homologous recombination technology is the most effective attenuation strategy, with gene deletion mutants derived from virulent strains achieving a VE of 73 % against mortality, 70 % against clinical signs, and 55 % against fever. Moreover, the efficacy and safety of LAVs are strongly influenced by the viral strain used as the vaccine backbone and the challenge strain used. A more comprehensive understanding of the antigenic, pathogenic, and immunogenic variations among ASF virus strains is crucial for the development of an effective and safe vaccine.

Interventions to support breastfeeding may help individuals and families initiate breastfeeding or breastfeed exclusively or for a prolonged period of time.

To systematically review the evidence on the benefits and harms of breastfeeding interventions to support the US Preventive Services Task Force in updating its 2016 recommendation.

Studies included in the previous review were reevaluated for inclusion and updated searches in MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials, and PsycINFO through June 3, 2024. Surveillance for new evidence in targeted publications through January 24, 2025.

Randomized clinical trials that evaluated a primary care-relevant intervention designed to support breastfeeding. Of 290 full-text articles reviewed, 90 met inclusion criteria.

Independent critical appraisal of all provisionally included studies. Data were independently abstracted by one reviewer and confirmed by another.

Child and maternal health outcomes, prevalence, and duration of any and exclusive breastfeeding, and harms related to interventions.

Ninety trials (N = 49 597) reported in 125 publications were included. The evidence represented individuals from diverse backgrounds and interventions that varied in timing, delivery, and duration. There was limited and mixed evidence on the effectiveness of breastfeeding support interventions on infant health outcomes (10 trials [n = 6592]) and maternal symptoms of anxiety, depression, and well-being (9 trials [n = 2334]). Pooled analyses indicated beneficial associations between breastfeeding support interventions and any or exclusive breastfeeding for up to and at 6 months (any breastfeeding: risk ratio, 1.13 [95% CI, 1.05-1.22]; 37 trials [n = 13 579] and exclusive breastfeeding: risk ratio, 1.46 [95% CI, 1.20-1.78]; 37 trials [n = 14 398]). There was no relationship between interventions and breastfeeding initiation or breastfeeding at 12 months.

The updated evidence confirms that breastfeeding support interventions can increase the prevalence of any or exclusive breastfeeding up to and at 6 months. Future efforts should focus on how to best provide this support consistently for all individuals making feeding decisions for their infants.

Odor identification correlates with Alzheimer's disease (AD) biomarkers, and its decline may emerge before measurable cognitive deficits-as early as the subjective cognitive decline (SCD) stage. We aimed to compare odor identification between SCD and cognitively normal (CN) stages and investigate whether cognitive differences moderate olfactory deficits.

A systematic search of four databases identified studies assessing olfactory identification and cognitive screening in individuals aged 50+. A random-effects meta-analysis was performed on 11 studies (660 SCD, 574 CN).

Individuals with SCD exhibited lower olfactory identification scores compared to CN participants (SMD = -0.67, 95%CI [-1.31, -0.03], p = .04). Meta-regression revealed a negative association (β = -1.79, p = .02) between cognitive and olfactory differences, indicating that greater cognitive decline was not consistently associated with greater olfactory deficits, lower odor identification scores in SCD occurred despite minimal cognitive differences across groups.

Odor identification is lower in pre-MCI individuals reporting SCD. Olfactory decline may emerge independently prior to measurable cognitive decline, supporting the role of odor identification as a screen for AD.

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.

The role of sodium-glucose co-transporter inhibitors (SGLT2i) in heart failure is well-established. However, evidence supporting their use in acute myocardial infarction remains limited.

Two independent researchers conducted a comprehensive literature review on PubMed and Embase until April 2024. They identified 14 articles, consisting of randomized controlled trials and observational studies, investigating the use of SGLT2i in acute myocardial infarction. The analysis focused on cardiovascular outcomes, including all-cause mortality, cardiovascular mortality, major adverse cardiovascular events (MACE), heart failure exacerbation, strokes, and recurrence of acute coronary syndrome.

Our pooled analysis of 19319 participants revealed a significant reduction in MACE [OR 0.50, 95% CI [0.36; 0.70], p-value= 0.0001] and hospitalization due to heart failure [OR 0.59 (0.43-0.79), P < 0.0004] in the SGLT2i group compared to the control group. In contrast, there were no statistically significant differences between the SGLT2i and control groups regarding all-cause mortality, cardiovascular mortality, recurrence of acute coronary syndrome, or new-onset arrhythmia.

Our study highlights that among patients with acute myocardial infarction, the use of SGLT2i reduces MACE and hospitalizations due to heart failure. However, there was no significant reduction in mortality, recurrence of acute coronary syndrome, or arrhythmia in the SGLT2i group.

Deprescribing has the potential to improve patient safety and quality of care by reducing polypharmacy and potentially inappropriate medications (PIMs), which in turn may reduce adverse drug events. Questions remain about the effectiveness of deprescribing interventions in outpatient settings.

To determine the association of deprescribing interventions with reducing medication count and PIMs in community-dwelling older adults.

Included studies were English-language human studies in PubMed and the Cochrane Library published from January 2019 to July 26, 2024, and results were supplemented with reference-mining and expert consultation.

Studies were eligible if they were solely or primarily about deprescribing, focused on community-dwelling adults, were multisite, used a randomized trial design, and reported on the primary or secondary outcome.

Two authors extracted study design, intervention characteristics, population characteristics, and follow-up. Outcomes were extracted by the statistician and checked by a second author. Meta-analyses were conducted using random effects with the Hartung-Knapp-Sidik-Jonkman method. The study was reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria.

The primary outcome was the number of PIMs or total medications, and the secondary outcome was proportion of persons prescribed at least 1 PIM.

Two authors independently screened 1586 titles from PubMed and Cochrane and 33 from other sources; 321 abstracts and 133 full-text studies were further reviewed, and disagreements were reconciled through discussion, resulting in 17 studies in 18 publications. A total of 8 studies of interventions targeting multiple medications were identified for primary outcome analysis; the random-effects pooled analysis found a mean difference of -0.14 (95% CI, -0.27 to -0.01) medications prescribed. A total of 6 studies of interventions targeting multiple medications were identified for secondary outcome analysis; the random effects pooled analysis found no significant reduction in the proportion of persons prescribed at least 1 PIM (odds ratio, 0.92 [95% CI, 0.74 to 1.14]).

This systematic review and meta-analysis found moderate-certainty evidence that deprescribing interventions were associated with reduced PIM and medication counts in community-dwelling older adults. While the individual-level association was very small, on an aggregated population level, the outcomes may be large, given the high prevalence of polypharmacy and PIMs in community-dwelling older adults.

This review aims to analyze sex-related differences in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS).

10 studies were retrieved from PubMed and Embase comparing outcomes between men and women admitted with AMI complicated by CS. Pooled log odds ratios (OR) were calculated for binary outcomes using the Mantel-Haenszel method, and Hedges' g with the inverse-variance method was used for continuous outcomes.

The primary endpoints were in-hospital mortality and 30-day mortality. The secondary endpoints were reinfarction rate, length of hospital stay (LOS), requirement of renal replacement therapy (RRT), and stroke (ischemic and hemorrhagic). Males exhibited a lower risk of in-hospital mortality (OR 0.77, 95 % CI 0.69-0.85, I2 = 97 %, p < 0.0001), 30-day mortality (OR 0.69, 95 % CI: 0.61-0.78, I² = 0 %, p < 0.0001) and stroke (OR 0.91, 95 % CI 0.87-0.95, I2 = 36 %, p < 0.0001) compared to females. In contrast, males were more likely to require renal replacement therapy (RRT) (OR 1.27, 95 % CI 1.09-1.48, I2 = 69 % p = 0.0017). However, there were no statistically significant differences between females and males in terms of reinfarction rate (OR 0.88, 95 % CI 0.66-1.18, I2 = 56 %, p = 0.3936) or length of hospital stay during hospitalization (Hedges's g 0.35 days, 95 % CI -0.38-1.07, I2 = 100 %, p = 0.34).

Females with AMI and CS have higher in-hospital mortality, 30-day mortality, and stroke risk than men. Men are more likely to require RRT. Further research is needed to understand underlying mechanisms and improve outcomes for both genders.

We conducted a systematic review and meta-analysis to compare venous couplers and hand-sewn techniques for venous anastomosis in head and neck reconstruction.

PubMed/MEDLINE and Scopus, databases were searched for relevant publications. Additionally, a manual search was performed in Google Scholar and through reference lists.

Retrospective and prospective cohort studies were included. Odds ratios (ORs) and mean differences (MD) were calculated with their 95% confidence intervals (CIs) for each study comparing the 2 groups (coupler vs hand). The inverse variance method was used to combine the effect sizes from the individual studies.

A total of 14,053 patients undergoing 14,270 head and neck free flap reconstructions were included from 52 studies. A total of 6080 flaps were performed using a coupling device for the venous anastomoses, while 8190 flaps were performed with the hand-sewn technique. No significant difference was found for the venous thrombosis rate (OR: 1.06, 95% CI: 0.65-1.72), and reoperation rate (OR: 0.93, 95% CI: 0.51-1.70), but a significantly lower failure rate was measured for the coupler group (OR = 0.34, 95% CI: 0.20-0.58). A nonsignificant lower operative time was found for venous anastomoses (MD: -20.5, 95% CI: -51.7 to 10.7) and total surgery (MD: -23.7, 95% CI: -344.3 to 296.8) for the coupler group.

Despite the slight advantages observed with venous couplers, the overall outcomes of both techniques are excellent, and the choice of anastomotic technique should be guided by surgeon preference.

To systematically synthesize the impact of autonomy and key theoretical models, including Self-Determination Theory (SDT), Technology Acceptance Model (TAM), Value Adoption Model (VAM), Theory of Planned Behavior (TPB), and Health Action Process Approach (HAPA), on health behavior and behavior change determinants, focusing on self-determination and intrinsic motivation as central drivers of independent health decisions.

A meta-analysis was conducted on 135 studies published between 2005 and 2023, with a total sample size of 53,242 participants. We searched the Web of Science and PubMed databases for relevant literature. The theoretical frameworks explored include SDT, TAM, VAM, TPB, and HAPA. Data analysis was performed using Review Manager 5.4.1 software, with effect size calculated as the standardized mean difference with 95% confidence intervals. Heterogeneity was evaluated using I2 statistics.

(1) SDT significantly impacted motivation, while TAM and VAM influenced perceived value [SMD = 0.96 > 0.8, 95% CI (0.68, 1.24), P < 0.001]. (2) Implementation intentions, action planning, and coping planning were key moderators of health behavior change (I2 = 65.4%). (3) HAPA's structured planning strategies positively impacted long-term health behavior changes.

Autonomy, self-determination, and intrinsic motivation play a crucial role in health behavior change. Integrating theoretical models such as SDT, TAM, VAM, and HAPA facilitates structured approaches to health interventions, emphasizing implementation intentions, action planning, and coping strategies.

Our study aims to investigate the associations between stress-related neural activity (SNA), a quantified imaging biomarker in processing stress responses assessed by 18F-FDG-PET/CT, and cardiovascular (CV) outcomes based on available evidence.

We searched databases from inception to December 1, 2024. Studies assessing the associations between SNA, as quantified by measuring FDG uptake values in the amygdala using 18F-FDG-PET/CT, and CV outcomes were included. Risk of bias was evaluated using the Newcastle-Ottawa Scale. Random-effects model was implemented for pooled effect sizes (ESs) and heterogeneity evaluation.

Ten studies with 3523 patients with 18F-FDG-PET/CT were included in our analysis (mean age: 58.5 years; 48.9% female). The ESs included in the analysis comprised hazard ratios (HR) and standardized mean differences (SMD). Among the studies reporting HR, 192 (11.5%) patients experienced composite adverse CV events during a mean follow-up period of 3.8 years. SNA significantly correlated with an increased risk of composite adverse CV events (pooled adjusted HR: 1.61, 95% confidence interval [CI]: 1.12, 2.32). Among the studies reported SMD, individuals experienced composite adverse CV events had significantly higher SNA values than those who did not (Hedges's g = 0.55, 95% CI: 0.14, 0.96).

SNA, as a noninvasive quantified indicator of processing stress responses assessed by brain 18F-FDG-PET/CT, is associated with an increased risk of CV outcomes. Further research is warranted to validate these findings and to investigate the clinical utility of SNA across various demographic groups.

Radiotherapy quality assurance (RTQA) is a critical aspect of randomized controlled trials (RCTs) and is associated with validity and reproducibility of the study findings. We conducted a systematic review and meta-analysis to assess the impact of RTQA results in contemporary RCTs on patient outcomes.

We searched MEDLINE and CENTRAL from January 2010, to April 2024, for papers that report on the impact of RTQA on patient outcomes in contemporary RCTs. We conducted random-effects meta-analyses to examine the association of radiotherapy protocol deviations with overall survival (OS), progression free survival (PFS), and locoregional recurrence (LR).

Of 2,723 citations, 16 publications reporting on 13 RCTs were included across various disease sites. Of 7,170 total randomized patients across 1,076 institutions in over 25 countries, 5,560 patients had radiotherapy quality data and were included in RTQA analyses. Most included RCTs (7/12; 58 %) conducted exclusively retrospective RTQA after treatment completion. Our meta-analyses found that protocol deviations may be associated with worse OS [HR = 1.65 (95 % CI: 1.23-2.22; p < 0.001)] and PFS [HR = 1.79 (95 % CI: 1.00-3.21; p = 0.03)]. No significant association was demonstrated between protocol deviations and LR [HR = 2.09 (95 % CI: 0.85-5.15; p = 0.108)].

Quality of radiotherapy continues to have an important, measurable impact on patient outcomes in oncology RCTs, and rigorous, real-time RTQA procedures may diminish these effects by standardizing RT. Future trials should provide patient outcome data in relation to RTQA and continue to report on the effect of protocol deviations in the context of modern RT techniques.

Post-mycobacterial residual lung abnormality (PMLA) from prior tuberculous (PTLA) or non-tuberculous mycobacterial (PNTLA) lung infections predisposes to chronic pulmonary aspergillosis (CPA). However, the prevalence of CPA in patients with PMLA remains uncertain. We aimed to determine the prevalence of CPA in patients with PMLA.

We performed a systematic search of PubMed and Embase databases up to January 31, 2025, to identify studies reporting CPA prevalence in patients with PTLA or PNTLA (excluding those with active tuberculosis). The pooled prevalence was calculated using frequentist meta-analysis (primary outcome), with Bayesian and trim-and-fill methods as sensitivity analyses. Study heterogeneity (I2) and publication bias were assessed. We performed multivariable meta-regression to evaluate factors affecting heterogeneity.

Thirty-one studies (4172 PTLA and 13,905 PNTLA) were included. Frequentist meta-analysis yielded a pooled CPA prevalence of 18% (95% confidence interval [CI], 11.6-25.4). Bayesian analysis with informative priors estimated prevalence of 7.1% (95% Credible Index, 4.5-10.4), and trim-and-fill adjustment for publication bias suggested prevalence to be 3.4% (95% CI, 0.69-7.7). On a multivariable analysis, we found CPA prevalence higher in hospital-based studies, high TB burden settings and studies with prospective or cross-sectional study designs; although CPA prevalence was higher in PTLA (23.1%) than in PNTLA (7%), it was not significantly different. We detected substantial heterogeneity (I2 = 98.8%) and publication bias.

There is a high prevalence of CPA in patients with PMLA, particularly in TB-endemic regions and hospital settings. Patients with PMLA should be routinely screened for CPA in high prevalence settings.

Valve-in-valve transcatheter aortic valve implantation (ViV-TAVI) has emerged as a feasible alternative to reoperative surgery in patients with degenerated surgical bio-prosthesis. However, data regarding the choice of valve type in ViV-TAVI remain inconclusive. This meta-analysis compares the procedural and clinical outcomes of self-expanding (SE) vs. balloon-expandable (BE) valves in ViV-TAVI. MEDLINE and Scopus were queried to identify studies reporting outcomes of ViV-TAVI by SE/BE valve type or comparing outcomes between SE or BE valves for ViV-TAVI. The primary outcome was incidence of all-cause mortality at 30 days. Data were presented as incidence of outcomes, analyzed via random effects model using inverse variance method with 95 % confidence intervals. Further incidence rates of primary and secondary outcomes were presented as subgroups of BE and SE, with comparison in incidence rates between the subgroups made using p-interaction of proportions. 27 studies with 13,182 patients (SE: 7346; BE: 5836) were included. There were no significant differences between the BE vs. SE valves in 30-day mortality (BE 4 % vs. SE 3 %, p = 0.44), 1-year mortality (BE 12 % vs. SE 10 %, p = 0.60), and moderate-to-severe AR at 1 year (BE 1 % vs. SE 3 %, p = 0.36). However, patients with SE valves had higher rates of new permanent pacemaker insertion (BE 4 % vs. SE 9 %, p = 0.0019). There were no significant differences in the incidence of 30-day safety outcomes, including stroke, AKI, coronary obstruction, major bleeding, and major vascular complications. Both BE and SE valve types showed comparable mortality and safety outcomes in ViV-TAVI, except pacemaker insertion, which was higher in SE compared with BE valves.

Recently, some studies have noted a negative cognitive impact on individuals in the aftermath of large-scale natural disasters; however, the causal relationship between disasters and cognitive/neurodegenerative effects remains widely unexplored. This review analyzes the impact of natural disasters on the development of cognitive decline (CD), all-cause dementia, and Alzheimer's disease (AD) in disaster-affected individuals. Studies reported from their inception to August 2023 were obtained via public online databases. All data presented in this review was derived from precalculated study results, data presented within/alongside articles, or statistics calculated using data obtained by contacting the articles' authors for ancillary information. Data from 28 studies, representing 4,606,561 individuals, 158,994 CD events, 179,694 dementia events, and 47,193 AD events was included for analysis. The pooled odds ratio (OR) and 95% confidence interval (CI) estimates showed that natural disasters significantly increased the risk of CD (OR: 1.25, CI: 1.20-1.30), all-cause dementia (OR: 1.07, CI: 1.05-1.08), and AD (OR: 1.07, CI: 1.05-1.10) in disaster victims as opposed to less- or non-impacted individuals. The greatest effects were noted following hurricanes, earthquakes with tsunamis, and heat waves. The findings from this meta-analysis indicate that natural disasters are significantly associated with the development of CD, all-cause dementia, and AD.

There is a growing interest of researchers in meta-analytic methods for comparing variances as a means to answer questions on between-group differences in variability. When measurements are fallible, however, the variance of an outcome reflects both the variance of the true scores and the error variance. Consequently, effect sizes based on variances, such as the log variability ratio (lnVR) or the log coefficient of variation ratio (lnCVR), may thus not only reflect between-group differences in the true-score variances but also differences in measurement reliability. In this article, we derive formulas to correct the lnVR and lnCVR and their sampling variances for between-group differences in reliability and evaluate their performance in simulation studies. We find that when the goal is to meta-analyze differences between the true-score variances and reliability differs between groups, our proposed corrections lead to accurate estimates of effect sizes and sampling variances in single studies, accurate estimates of the average effect and the between-study variance in random-effects meta-analysis, and adequate type I error rates for the significance test of the average effect. We discuss how to deal with problems arising from missing or imprecise group-specific reliability estimates in meta-analytic data sets and identify questions for further methodological research.

The global burden of stroke is increasing every year. Residual impairments from stroke reduce the future independence of affected patients while also increasing their susceptibility to oral health-related diseases. Oral healthcare prevention programs (OHCP) are vital in maintaining acceptable oral hygiene during rehabilitation. Dysphagia among stroke elevates the risk of ingesting oral opportunistic pathogens, potentially leading to severe conditions.

A systematic search was conducted in three main databases (Medline, EMBASE, CENTRAL) until November 29th, 2022.

We included randomized clinical trials that measure the effect of OHCP on oral health and oral opportunistic pathogens. After the systematic search (7608 articles), we conducted title/abstract selection by two independent authors, followed by full-text selection. In both cases, Cohen's kappa was calculated. Finally, we found 15 articles that were eligible for analysis.

The plaque index showed a slight but non-significant reduction with the OHCP program (SMD= -2.77, CI:6.6-1.06). In terms of the risk of oral yeast detection, there was a statistically non-significant difference between the intervention and control groups at short-term and after a 3-month follow-up (RR: 1.06, 95 % CI: 0.20;5.69; RR:0.98 CI: 0.33; 2.93), respectively. For S.aureus and AGNB, there was no statistically significant difference in short-term evaluation (RR: 0.89 CI: 0.07; 11.99; RR:0.77 CI: 0.00; 888.18), respectively.

Current evidence did not identify that regular OHCP had a beneficial effect on oral pathogen-related diseases.

CRD42022346788 CLINICAL SIGNIFICANCE: Regular oral health care, including assistance from a dental hygienist in stroke units, is essential for preventing oral health-related diseases. Integrating into post-stroke rehabilitation can enhance overall quality of life and well-being.

We conducted a systematic review of randomized, controlled trials (RCTs) to generate more precise estimates of the efficacy and safety of oral versus intravenous antibiotic therapy for Staphylococcus aureus bacteremia or endocarditis.

MEDLINE, Embase, the Cochrane Library, and Web of Science databases were searched through February 2024. RCTs were included if they compared oral versus intravenous antibiotic therapy for S. aureus bacteremia or endocarditis and appropriately reported outcomes for each group. Risk of bias was assessed using the revised Cochrane tool for assessing risk of bias in randomized trials. Heterogeneity between studies was evaluated with Cochran's Q-statistic and I2 test. Treatment effects were summarized with pooled risk ratios using a random effects model meta-analysis (PROSPERO CRD42024481512).

Only four RCTs met criteria for inclusion in meta-analysis. Among participants assessed for treatment failure, there was no difference between oral and intravenous therapy groups (risk ratio [RR], 0.99; 95% confidence interval [CI], .63-1.57; I2 = 0%). There was also no significant difference in adverse events between oral and intravenous therapy groups (RR, 0.65; 95% CI, .07-5.94; I2 = 74%); however, the confidence interval was wide, and heterogeneity was high.

In this systematic review of RCTs comparing oral with intravenous antibiotic therapy for S. aureus bacteremia or endocarditis, few studies met the eligibility criteria for inclusion. Meta-analysis of these studies suggests that transitioning from intravenous to oral therapy is likely effective in a subgroup of carefully selected patients. Additional randomized trials are necessary before transition to oral therapy can be routinely recommended.

We did a systematic review and meta-analysis of trials of treatment for rifampicin-susceptible tuberculosis to evaluate the representativeness of participants compared with characteristics of the global population of people with tuberculosis, and the adequacy of adverse event reporting. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews from Jan 1, 2000, to Dec 10, 2023, for trials that had greater than or equal to 50 participants per arm and had follow-up to at least treatment completion. Studies were excluded if they compared different formulations of standard drugs (eg, fixed-dose combination tablets); aimed to primarily enrol participants with isoniazid-resistant or rifampicin-resistant tuberculosis; evaluated treatment to prevent tuberculosis infection; tested dietary or vitamin supplementation; tested vaccines or other immune-based interventions; tested adherence support or system-related mechanisms; or enrolled participants with tuberculosis, but tuberculosis treatment itself was not randomised (ie, trials of the timing of antiretroviral therapy initiation). Trial protocols and trials not available in English were also excluded. The outcomes were inclusion and exclusion criteria, characteristics of participants, and adverse event reporting. This systematic review was prospectively registered (PROSPERO ID CRD42022373954). We identified 7328 articles, of which 40 were eligible for analysis. Demographic characteristics, including sex, were reported for 20 420 participants, of which 6663 (33%) were female and 13 757 (67%) were male. We found that people who were greatly affected by the global tuberculosis pandemic were frequently excluded from participation: of the 40 trials, 25 (62·5%) excluded people younger than 18 years, 12 (30·0%) excluded people aged 65 years or older, 34 (85·0%) excluded pregnant or lactating people, 12 (30·0%) excluded people with diabetes, and 11 (27·5%) excluded people with excessive alcohol use, drug use, or both. In the nine trials that reported enrolment of people with diabetes, the pooled proportion of participants with diabetes (9%) was lower than global estimates for the proportion of people with tuberculosis who have diabetes (16%). There were important gaps in adverse event ascertainment, analysis, and interpretation. Of the 40 trials, a minority reported measures of regimen acceptability: 14 (35·0%) reported study withdrawal, eight (20·0%) reported temporary and 16 (40·0%) reported permanent discontinuation of assigned therapy, and 11 (27·5%) reported adherence. Participants in trials were not representative of the global tuberculosis pandemic in demographic and clinical characteristics, restricting the generalisability of trial outcomes. Adverse event reporting could be improved through the use of patient-reported outcomes, standardised definitions of key outcomes, and uniform reporting of measures of regimen acceptability. There was no funding for this systematic review.

Is the probability of pregnancy different between women using biosimilars versus the originator of follitropin alfa for ovarian stimulation in ART?

Meta-analysis of eight randomized clinical trials (RCTs) suggests that live birth, clinical, and ongoing pregnancy rates are significantly lower with biosimilars of follitropin alfa compared to the originator.

All biosimilars of follitropin alfa have received regulatory approval by demonstrating non-inferiority in the number of retrieved oocytes compared to the originator. Nevertheless, the most clinically relevant outcome in ART for both clinicians and patients is live birth. A meta-analysis published in 2021 suggested that biosimilars of follitropin alfa are associated with lower live birth rates compared to the originator. Since then, more relevant RCTs have been published, and thus an updated critical synthesis of the available evidence is urgently warranted.

A systematic review and meta-analysis were performed to compare biosimilars versus the originator of follitropin alfa in women undergoing ovarian stimulation for ART. A literature search was conducted until January 2024 in MEDLINE, Embase, Cochrane CENTRAL, Scopus, Web of Science, WHO, Clinicaltrials.gov, and others to identify eligible RCTs. The primary outcome was live birth. Secondary outcomes included clinical and ongoing pregnancy, duration of gonadotrophin administration and total FSH dose, number of oocytes retrieved, and ovarian hyperstimulation syndrome (OHSS).

Data were extracted independently by two reviewers. Quality was assessed using the RoB-2 Tool by Cochrane, and a sensitivity analysis was performed by excluding studies having high risk of bias. Meta-analysis was performed using the random or fixed effects model depending on the presence or not of significant (>50%) statistical heterogeneity (I2). Results were combined using the intention-to-treat principle and are reported as risk ratio (RR) or weighted-mean-difference (WMD) with 95% CIs.

Eight RCTs (n = 2987) (published between 2015 and 2023) were identified, assessing seven biosimilar products of follitropin alfa. The number of patients included in the eligible studies ranged from 100 to 1100. Three of the RCTs were deemed to be at high risk of bias. The duration of gonadotrophin administration was shorter in the biosimilars group (WMD: -0.19 days, 95% CI: -0.34 to -0.05; I2 = 0%, 5 studies, n = 2081), while no difference was observed in the total dose of FSH (WMD: -34.69 IUs, 95% CI: -74.54 to 5.16; I2 = 15.53%, 5 studies, n = 2081). No difference was observed in the number of oocytes retrieved (WMD: 0.27, 95% CI: -0.43 to 0.96; I2 = 10.7%, 6 studies, n = 1527) and OHSS rates (RR: 1.17, 95% CI: 0.90-1.52; I2 = 0%, 8 studies, n = 2986) between the two groups. A significantly lower live birth rate was observed using the biosimilars of follitropin alfa compared to the originator in women undergoing ovarian stimulation for ART (RR: 0.83, 95% CI: 0.72-0.96; I2 = 0%, 6 studies, n = 2335; moderate certainty of evidence). Similarly, clinical pregnancy (RR: 0.82, 95% CI: 0.73-0.92; I2 = 0%, 7 studies, n = 2876; low certainty of evidence) and ongoing pregnancy rates (RR: 0.81, 95% CI: 0.70-0.94; I2 = 0%, 7 studies, n = 1886; low certainty of evidence) were lower in the biosimilars group. These results were not materially altered in the sensitivity analyses performed where studies deemed at high risk of bias were excluded.

This meta-analysis included RCTs evaluating seven different biosimilars of follitropin alfa; however, pooled data appeared to be homogeneous. No data were available comparing biosimilars of follitropin alfa with the originator regarding cumulative live birth rate per aspiration or the probability of live birth in frozen thawed cycles. The population examined in the eligible RCTs includes mainly normal responders and no RCTs were identified focusing on poor or high responders.

Clinicians should be informed that although biosimilars of follitropin alfa produce similar number of oocytes with the originator, pregnancy rates after a fresh transfer are likely to be lower. Future research should focus on optimizing the production and use of biosimilars of follitropin alfa, so that they lead to pregnancy rates comparable to the originator.

No external funding was used for this study. K.I.K. and A.S. have no competing interest to disclose. E.M.K. reports personal fees and non-financial support from Merck, Ferring, IBSA, and Vianex. B.W.M. has been supported by an investigator grant from NHMRC, has received consulting fees from Organon, Merck, and Norgine, research support and non-financial support from Merck KGaA, Darmstadt, Germany. B.W.M. also reports having stocks from OBsEva. C.A.V. reports grants, personal fees, and non-financial support from Merck KGaA, Darmstadt, Germany, personal fees, and non-financial support from Merck, Sharpe and Dohme, personal fees and non-financial support from Organon, grants and non-financial support from Ferring, personal fees from IBSA, and personal fees and non-financial support from Gedeon Richter and Vianex.

Protocol for the systematic review registered in The International Prospective Register of Systematic Reviews (PROSPERO; CRD42024498237).

To determine whether a liberal transfusion strategy (≥ 9 g/dL) improves neurological outcomes in adults with acute brain injury (ABI).

We systematically searched MEDLINE, EMBASE, the Cochrane Library, and trial registries for randomized controlled trials comparing liberal (≥ 9 g/dL) vs. restrictive (≥ 7 g/dL) transfusion in adults with ABI (traumatic brain injury, subarachnoid hemorrhage, intracranial hemorrhage) and Glasgow Coma Scale ≤ 13. Frequentist, Bayesian, and trial sequential analyses were used. The primary outcome was favorable neurological status at 180 days.

Four randomized controlled trials (N = 1853; 922 liberal, 931 restrictive) were included. The pooled frequentist risk ratio (RR) for favorable neurological outcome was 0.84 (95% CI 0.65-1.09; I2 = 58%). In a pre-specified sensitivity analysis including only low-risk-of-bias trials, the results suggested a potential benefit in favor of the liberal strategy (RR 0.74 [95% CI 0.63-0.87]) with no heterogeneity (I2 = 0%). Subgroup analyses for patients with traumatic brain injury or stratified by initial Glasgow coma scale were consistent with the main findings. Bayesian analyses showed that the estimated treatment effect depended on the assumptions and priors used, with an unfavorable prior derived from one trial with distinct protocol appearing less likely than neutral or favorable priors. Trial sequential analysis indicated that current evidence is insufficient to confirm a definitive effect. Secondary outcomes did not differ significantly between groups.

This review did not provide definitive evidence of a neurological benefit from liberal transfusion strategies in acute brain injury. Both frequentist and Bayesian analyses highlight the influence of a single trial on the overall effect estimate and heterogeneity. However, sensitivity analyses excluding this trial and focusing on studies with low risk of bias suggested that liberal transfusion strategies could improve neurological outcomes. Future research should focus on identifying patient subgroups most likely to benefit, guiding a more individualized approach.

Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used to treat refractory cardiac arrest, although with variable results in survival and neurological outcomes. The intra-aortic balloon pump (IABP) showed mixed effects on survival in veno-arterial extracorporeal membrane oxygenation. Furthermore, the impact of IABP on survival and neurological outcomes in ECPR recipients has yet to be fully investigated.

We searched relevant databases for studies concerning ECPR recipients and intra-aortic balloon pump with information on survival and neurological outcomes. The inverse variance method (95 % confidence intervals) was used to determine the odds ratios of outcomes. We decided on a priori use of the random-effects model with the Hartung-Knapp adjustment.

We included in our analysis nine cohort studies dealing with a total of 4994 patients. The association of IABP with ECPR was associated with a survival benefit compared to ECPR alone: 1029/3124 (32.9 %) patients survived in the ECPR+IABP group versus 379/1870 (20.2 %) in the ECPR group, OR 1.94, 95 % CI [1.36 to 2.77]. Survival with good neurological outcome was analyzed in 4 studies for 4018 patients. The association of ECPR and IABP was associated with a not significant advantage in survival with favorable neurological outcome compared with ECPR alone: 555/2687 (20.7 %) patients with good neurological outcome in the group of ECPR+IABP versus 149/1331 (11.2 %) patients in the group of ECPR, OR 1.33, 95 % CI [0.61 to 2.92].

The association of IABP and ECPR significantly increases survival rates compared to ECPR alone. Nevertheless, the impact on favorable neurological outcomes remains uncertain.

Gamma-glutamyl transferase (GGT) has been shown to have associations with several diseases including cancers. Previous studies have investigated the effect of GGT levels on the gastrointestinal (GI) cancer incidence. We aim to systematically investigate these studies to provide better insights into the interrelationship between GGT and GI cancers.

Online databases were searched to find relevant studies investigating different GGT levels' effects on the incidence of GI cancers including colorectal, esophageal, liver, pancreas, gastric, and biliary duct cancers. Random-effect meta-analysis was conducted to pool the hazard ratios (HRs) of GGT quartiles (Qs) effect on cancer incidence.

A total of 26 studies were included in the final review, 12 of which underwent meta-analysis that investigated 11 million patients. Based on the meta-analysis, Q4 patients had a 69% higher hazard of GI cancer incidence (HR 1.69, 95% CI 1.41-2.02, p-value < 0.001). The hazard ratio significance was also similar for Q3 (HR 1.22, 95% CI 1.15-1.30, p-value < 0.001) and Q2 (HR 1.10, 95% CI 1.05-1.16, p-value =0.002) of GGT. Colorectal and liver cancers showed a higher hazard ratio among Q2, Q3, and Q4 of GGT compared to Q1. In pancreas and bile duct cancers, only Q4 of GGT had significantly higher HR. Q3 and Q4 of GGT levels had statistically significant associations with gastric cancer incidence.

Higher GGT levels correlate with higher rates of GI cancer incidence, especially in colorectal and hepatic cancers. Future studies should investigate this biomarker's potential role in risk assessment for digestive cancers.

Electroencephalogram burst suppression can be associated with postoperative delirium; however, the results of relevant studies are discrepant. This systematic review and meta-analysis aimed to assess the association between intraoperative burst suppression and postoperative delirium in adult surgical patients.

PubMed, MEDLINE, Embase, Google Scholar, and the Cochrane Central Register of Controlled Trials were systematically searched and updated in May 2023. The authors included cohort studies, case-control studies, and randomized controlled studies reporting on postoperative delirium incidence with documented intraoperative burst suppression in adults receiving general anesthesia for any surgery. The primary outcome was the pooled odds ratio for postoperative delirium in cases with intraoperative burst suppression compared to those without burst suppression, calculated using a random-effects model. Two independent investigators extracted the data. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (registration No. CRD42022326479); the results were reported according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.

Fourteen studies (6,435 patients) were included in the analysis. The overall incidence of postoperative delirium was 21.1% (1,358 of 6,435). Patients with intraoperative burst suppression had a higher incidence of postoperative delirium than those without burst suppression (pooled odds ratio, 1.492; 95% CI, 1.022 to 2.178; I2 = 44%; 95% CI, 0 to 75%; τ2 = 0.110). The intraoperative duration of burst suppression was significantly longer in patients who developed postoperative delirium (standardized mean difference, 0.462; 95% CI, 0.293 to 0.632; I2 = 63%; 95% CI, 16 to 84%; τ2 = 0.027). The burst suppression ratio was significantly higher in the delirium group (standardized mean difference, 0.150; 95% CI, 0.055 to 0.245; I2 = 0%; 95% CI, 0 to 85%; τ2 = 0.00).

The meta-analysis suggests an association between intraoperative burst suppression and postoperative delirium; however, the quality of evidence was very low. The limited number of studies and substantial heterogeneity across them emphasize the need for further high-quality studies to establish a more robust conclusion.

Recurrent pregnancy loss (RPL) represents a complication of pregnancy occurring in 1%-3% of all couples trying to conceive. About 50%-60% of RPL cases remain idiopathic, therefore therapeutic strategies seem empirical and based on unproven evidence. We investigated the efficacy of corticosteroids in women with RPL. We conducted a systematic review and meta-analysis, up to August 2024, in the PubMed, Scopus, and Web of Science databases, including studies on idiopathic RPL women and comparing corticosteroids versus control treatment. Primary outcome was the ongoing pregnancy rate beyond 12 weeks of gestation; secondary outcomes were live birth rate (LBR), stillbirth, birth weight, incidence of preeclampsia and/or gestational diabetes, gestational age at delivery, and fetal abnormalities. Four studies comprising 417 RPL women randomly assigned to steroid or control treatment were included. We found that oral corticosteroids significantly increase the ongoing pregnancy rate beyond 12 weeks of gestation compared to the control group (log OR [odds ratio] = 1.49 [0.32, 2.67], p = 0.01), with high heterogeneity (I2 = 75%), and improve LBR (log OR = 0.9 [0.11, 1.69], p = 0.03), with low heterogeneity (I2 = 0.05%). However, the limited number of studies significantly limits the strength of the findings. Also, the benefit/risk assessment of the use of corticosteroids in early pregnancy for RPL is still unclear.

Pneumococcal infections are a serious health issue associated with increased morbidity and mortality. This systematic review evaluated the efficacy, effectiveness, immunogenicity, and safety of the pneumococcal conjugate vaccine (PCV)15 compared to other pneumococcal vaccines or no vaccination in children and adults. We identified 20 randomized controlled trials (RCTs). A meta-analysis of six RCTs in infants showed that PCV15 was non-inferior compared with PCV13 for 12 shared serotypes. Based on a meta-analysis of seven RCTs in adults, PCV15 was non-inferior to PCV13 for 13 shared serotypes. For the unique PCV15 serotypes, 22F and 33F, immune responses were higher in infants and adults vaccinated with PCV15 compared to those receiving PCV13. Regarding safety, meta-analyses indicated comparable risks of adverse events between PCV15 and PCV13 in infants. Adults receiving PCV15 had a slightly higher risk of adverse events, though serious events were similar between groups.

Mean platelet volume (MPV) is a widely available laboratory index, however its prognostic significance in patients with coronary artery disease (CAD) is still unclear. We intended to investigate and pool the evidence on the prognostic utility of admission MPV in predicting clinical outcomes in patients with CAD.

PubMed, Web of Science, and Scopus were the major databases used for literature search. The risk of bias was assessed using the quality in prognostic factor studies. We used random-effects pairwise analysis with the Knapp and Hartung approach supported further with permutation tests and prediction intervals (PIs).

We identified 52 studies with 47,066 patients. A meta-analysis of nine studies with 14,864 patients demonstrated that one femtoliter increase in MPV values was associated with a rise of 29% in the risk of long-term mortality (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.22-1.37) in CAD as a whole. The results were further supported with PIs, permutation tests and leave-one-out sensitivity analyses. MPV also demonstrated its stable and significant prognostic utility in predicting long-term mortality as a linear variable in patients treated with percutaneous coronary intervention (PCI) and presented with acute coronary syndrome (ACS) (HR 1.29, 95% CI 1.20-1.39, and 1.29, 95% CI 1.19-1.39, respectively).

The meta-analysis found robust evidence on the link between admission MPV and the increased risk of long-term mortality in patients with CAD patients, as well as in patients who underwent PCI and patients presented with ACS.

To compare the risk of hospital admissions with infections and infections not in hospital in children born by caesarean section with children born by vaginal birth.

Medline, Embase, and PubMed were searched with no restriction on start date up to 12 February 2024.

Observational studies were included that reported the association between caesarean section and vaginal birth in relation to the risk of infections (both those that lead to hospital admission and those that do not) up to 18 years of age. Studies were excluded if they were not representative of a general population or if they focused on congenital, neonatal, or vertically acquired infections. No restrictions were made for language, publication date, or setting.

Findings for hospital admissions with infection were synthesised by meta-analyses of specific infection outcomes and type of caesarean birth (emergency v elective) and findings for other infections (ie, infection episodes reported by parents and primary care visits) by direction of effect. Risk of bias was assessed using the ROBINS-E tool and the overall certainty of evidence through the GRADE framework.

31 eligible studies of over 10 million children were included. Findings were from population-based birth cohorts and registry data linkage studies in high income countries. Cohort sizes ranged from 288 to 7.2 million and follow up age was from one to 18 years. Outcomes included overall and specific clinical categories of infection. From studies of overall admission to hospital with infection, the proportion of children admitted ranged between 9-29% across exposure groups. In random-effects meta-analyses combining hazard ratios, children delivered by caesarean section had an increased rate of hospital admission with infections overall and in three common clinical infection categories: (1) overall admissions to hospital with infection (emergency caesarean section: n=6 study populations, hazard ratio 1.10 (95% confidence interval 1.06 to 1.14), τ 2=0.0009, I2=96%; elective caesarean section: n=7, 1.12 (1.09 to 1.15), τ 2=0.0006, I2=88%); (2) admission to hospital for upper respiratory infections (emergency caesarean section: n=7, 1.11 (1.09 to 1.13), τ 2=0.0003, I2=73%; elective caesarean section: n=7, 1.16 (1.12 to 1.20), τ 2=0.0012, I2=89%); (3) admission to hospital for lower respiratory infections (emergency caesarean section: n=8, 1.09 (1.06 to 1.12), τ 2=0.0010, I2=88%; elective caesarean section: n=8, 1.13 (1.10 to 1.16), τ 2=0.0009, I2=84%); (4) admission to hospital for gastrointestinal infections (emergency caesarean section: n=7, 1.19 (1.13 to 1.26), τ 2=0.0025, I2=86%; elective caesarean section: n=7, 1.20 (1.15 to 1.25), τ 2=0.0009, I2=67%). Eight of 11 studies of other infections suggested an increased risk of their primary infection outcome in those born by caesarean section. Risk of bias concerns primarily related to confounding.

Findings from high income countries showed a consistent association between caesarean section birth and greater risk of infections in children across various settings. Limitations of existing studies include the potential for unmeasured confounding, specifically confounding by indication, and a scarcity of studies from low and middle income countries.

PROSPERO (CRD42022369252).

Untreated infective endocarditis (IE) is uniformly fatal. The practice of combination antibiotic therapy for IE is recommended by treatment guidelines but largely unsupported by high-quality evidence. This study aimed to assess the efficacy of combination antibiotic therapy compared to monotherapy in IE through a systematic review and meta-analysis. We systematically searched MEDLINE, Embase, Cochrane, Web of Science, and CINAHL from inception to 29 July 2024. Studies reporting mortality outcomes of combination therapy versus monotherapy in adult patients with IE were included. Non-English papers and studies with less than 10 patients in the combination therapy group were excluded. Two reviewers independently assessed the studies and extracted relevant data. Summaries of odds ratios (ORs) with 95% confidence intervals (CIs) were evaluated using random-effects models. Out of 4545 studies identified, 32 studies (involving 2761 patients) met the inclusion criteria for the meta-analysis. There was no significant difference in the risk of all-cause mortality between the monotherapy and combination therapy groups (OR = 0.90; 95% CI = 0.67-1.20). Similar results were observed in subgroup analyses based on mortality time points, bacterial species, publication date, and type of study. Studies conducted in Europe reported a statistically significant decrease in overall mortality risk with combination therapy (OR = 0.67; 95% CI = 0.51-0.89), though this result was driven entirely by a single outlier study. Combination antibiotic therapy in patients with IE was not associated with reduced mortality.

Retrospective studies suggest that immunosuppressive treatment of immune-related adverse events (irAEs) impairs survival in patients with melanoma who received immune checkpoint inhibitors. Here, we study this association across tumor types using data from six international phase II/III registrational trials.

A post hoc analysis was performed on individual patient data from the anti-programmed cell death-1 (anti-PD-1) + anti-cytotoxic T lymphocyte-associated protein-4 (anti-CTLA-4) treatment arms of six clinical trials (CheckMate-067, -142, -214, -648, -743, and -9LA). Among patients who received systemic immunosuppression for treatment-related adverse events (trAEs), associations of peak and cumulative corticosteroid dose, and use of second-line immunosuppression with overall survival (OS) and progression-free survival (PFS) were assessed using multilevel Cox regression with adjustment for age and sex.

Of the 1,959 patients who received anti-PD-1 + anti-CTLA-4 therapy, 834 patients who were treated with immunosuppression for trAEs were included. Eight hundred and thirty-two patients (100%) received corticosteroids and 81 patients (10%) received second-line immunosuppressants. High corticosteroid peak dose was associated with worse PFS: adjusted hazard ratio (HRadj), 1.15 (95% CI, 1.02 to 1.29) for 1 versus 0.5 mg/kg prednisolone and HRadj, 1.43 (95% CI, 1.05 to 1.96) for 2 versus 0.5 mg/kg. Similar effects were observed for OS: HRadj, 1.21 (95% CI, 1.06 to 1.39) and HRadj, 1.66 (95% CI, 1.17 to 2.37) for 1 and 2 versus 0.5 mg/kg, respectively. Cumulative corticosteroid dose was not associated with survival. HRadj of use of second-line immunosuppression was 1.23 (95% CI, 0.90 to 1.68) for PFS and 1.25 (95% CI, 0.88 to 1.77) for OS.

Higher corticosteroid peak dose for trAEs is associated with worse survival across tumor types, while cumulative dose is not. Too few patients received second-line immunosuppressants to confirm or reject an association with survival. These data argue for a reconsideration of irAE management approaches, starting with lower corticosteroid dose whenever feasible.

In sparse data meta-analyses (with few trials or zero events), conventional methods may distort results. Although better-performing one-stage methods have become available in recent years, their implementation remains limited in practice. This study examines the impact of using conventional methods compared to one-stage models by re-analysing meta-analyses from the Cochrane Database of Systematic Reviews in scenarios with zero event trials and few trials. For each scenario, we computed one-stage methods (Generalised linear mixed model [GLMM], Beta-binomial model [BBM], Bayesian binomial-normal hierarchical model using a weakly informative prior [BNHM-WIP]) and compared them with conventional methods (Peto-Odds-ratio [PETO], DerSimonian-Laird method [DL] for zero event trials; DL, Paule-Mandel [PM], Restricted maximum likelihood [REML] method for few trials). While all methods showed similar treatment effect estimates, substantial variability in statistical precision emerged. Conventional methods generally resulted in smaller confidence intervals (CIs) compared to one-stage models in the zero event situation. In the few trials scenario, the CI lengths were widest for the BBM on average and significance often changed compared to the PM and REML, despite the relatively wide CIs of the latter. In agreement with simulations and guidelines for meta-analyses with zero event trials, our results suggest that one-stage models are preferable. The best model can be either selected based on the data situation or, using a method that can be used in various situations. In the few trial situation, using BBM and additionally PM or REML for sensitivity analyses appears reasonable when conservative results are desired. Overall, our results encourage careful method selection.

Individual participant data (IPD) meta-analysis projects obtain, harmonise, and synthesise original data from multiple studies. Many IPD meta-analyses of randomised trials are initiated to identify treatment effect modifiers at the individual level, thus requiring statistical modelling of interactions between treatment effect and participant-level covariates. Using a two-stage approach, the interaction is estimated in each trial separately and combined in a meta-analysis. In practice, two complications often arise with continuous outcomes: examining non-linear relationships for continuous covariates and dealing with multiple time-points. We propose a two-stage multivariate IPD meta-analysis approach that summarises non-linear treatment-covariate interaction functions at multiple time-points for continuous outcomes. A set-up phase is required to identify a small set of time-points; relevant knot positions for a spline function, at identical locations in each trial; and a common reference group for each covariate. Crucially, the multivariate approach can include participants or trials with missing outcomes at some time-points. In the first stage, restricted cubic spline functions are fitted and their interaction with each discrete time-point is estimated in each trial separately. In the second stage, the parameter estimates defining these multiple interaction functions are jointly synthesised in a multivariate random-effects meta-analysis model accounting for within-trial and across-trial correlation. These meta-analysis estimates define the summary non-linear interactions at each time-point, which can be displayed graphically alongside confidence intervals. The approach is illustrated using an IPD meta-analysis examining effect modifiers for exercise interventions in osteoarthritis, which shows evidence of non-linear relationships and small gains in precision by analysing all time-points jointly.

Collecting data for an individual participant data meta-analysis (IPDMA) project can be time consuming and resource intensive and could still have insufficient power to answer the question of interest. Therefore, researchers should consider the power of their planned IPDMA before collecting IPD. Here we propose a method to estimate the power of a planned IPDMA project aiming to synthesise multiple cohort studies to investigate the (unadjusted or adjusted) effects of potential prognostic factors for a binary outcome. We consider both binary and continuous factors and provide a three-step approach to estimating the power in advance of collecting IPD, under an assumption of the true prognostic effect of each factor of interest. The first step uses routinely available (published) aggregate data for each study to approximate Fisher's information matrix and thereby estimate the anticipated variance of the unadjusted prognostic factor effect in each study. These variances are then used in step 2 to estimate the anticipated variance of the summary prognostic effect from the IPDMA. Finally, step 3 uses this variance to estimate the corresponding IPDMA power, based on a two-sided Wald test and the assumed true effect. Extensions are provided to adjust the power calculation for the presence of additional covariates correlated with the prognostic factor of interest (by using a variance inflation factor) and to allow for between-study heterogeneity in prognostic effects. An example is provided for illustration, and Stata code is supplied to enable researchers to implement the method.

Necrotizing enterocolitis (NEC) is a known cause of morbidity and mortality in infants with congenital heart disease (CHD), but reports about the burden of cardiogenic NEC frequently conflict. To synthesize the extant literature on the incidence, risk factors, and prognosis of NEC in patients with CHD. Medline, Cochrane, and EMBASE were searched from 1946 through 2023 for studies of NEC in infants 0-12 months of age with CHD. Risk of bias was assessed with validated tools for incidence and risk factors. Pooled estimates were meta-analyzed by risk of bias or synthesized without meta-analysis. Eighty-six studies with a total of 67,924 participants were included. The incidence of cardiogenic NEC was 7.1% (95% CI 4.7-10.5%) in term infants and 13.0% (10.2-16.5%) in low birthweight preterm infants. NEC required surgery in 0.8% (0.5-1.1%) of term and 2.7% (2.0-3.7%) of premature infants, respectively. Only gestational age and birth weight were consistently associated with risk of NEC. Restricting pooled estimates to studies of moderate or low risk of bias significantly reduced the number of studies included. Necrotizing enterocolitis is a common cause of morbidity in infants with CHD, but additional research is needed to determine which infants are at highest risk of developing NEC and would benefit most from a change in management. This systematic review and meta-analysis was conducted according to a prespecified protocol registered at the Prospective Register of Systematic Reviews (CRD42021282114).

Is anti-Black discrimination concentrated among a discriminatory few, or widespread across many decision-makers? The handful of studies that have addressed this question have reached divergent conclusions, with some suggesting that discrimination follows the 80/20 rule (i.e., a Pareto distribution) and others suggesting that discrimination is normally distributed. This paper explores the distribution of discrimination in hiring, housing, and judicial decisions. Study 1 examined the distribution of anti-Black discrimination in judges' repeated sentencing decisions. The distribution of discrimination was more consistent with a normal distribution than a Pareto distribution. In Study 2, meta-analyses of hiring and housing field experiments revealed anti-Black discrimination in more than 80% of studies. Simulations of widespread discrimination using a normal distribution were more consistent with these experimental data than were simulations of concentrated discrimination using a Pareto distribution. These findings suggest that discrimination is not concentrated in the behaviors of a few highly biased individuals.

Although vaccination is considered the most effective weapon against influenza, coverage rates, national vaccination policies, and funding vary largely around the globe. Despite their huge potential for achieving herd immunity, child-focused national vaccination strategies that favor pain-free nasal vaccines are uncommon. CENTRAL, Embase, and MEDLINE were last searched on November 13, 2023. Active-controlled randomized controlled trials comparing the live-attenuated intranasal vaccine with the inactivated intramuscular influenza vaccine in children were included. Event rates of laboratory-confirmed influenza virus infection, all-cause mortality, hospitalization, serious adverse events, adverse events, and financial outcomes were extracted based on the PRISMA 2020 Guideline. PROSPERO: CRD42021285412. Pooled odds ratios (ORs) with 95% confidence intervals (CI) were calculated using the random-effects model when at least three comparable outcomes were available. We found no significant difference between quadrivalent live-attenuated intranasal and trivalent inactivated intramuscular (OR = 1.48; 95% CI 0.49-4.45) or between trivalent live-attenuated intranasal and inactivated intramuscular vaccines (OR = 0.77, CI = 0.44-1.34) regarding their efficacy. However, the subgroup analysis of large, multi-center trials indicated that the trivalent live attenuated intranasal influenza vaccine was superior to the trivalent inactivated intramuscular influenza vaccine (12,154 people, OR = 0.50, CI = 0.28-0.88). Only 23 "vaccine-related serious adverse events" were recorded among 17 833 individuals, with no significant difference between methods. The widespread initiation of pediatric national flu vaccination programs prioritizing the live-attenuated intranasal influenza vaccine would be beneficial. Multi-continent, high-quality studies that include children younger than two years old and those living in subtropical and tropical regions are needed to further enhance our understanding.

Individuals with an autism spectrum disorder (ASD) diagnosis show impairment in executive function (EF). However, findings are mixed regarding differences in the age effect on EF between autistic individuals and persons with typical development (TD). Questions remain regarding whether the age-related trajectories of EF in ASD are the same as or different from those in TD. To bridge this knowledge gap, we conducted a systematic review and meta-analyses of longitudinal studies that compared age-related changes in EF between ASD and TD groups (preregistration: osf.io/j5764). A literature search was conducted using PubMed, PsycINFO, and Web of Science on January 29, 2024. After screening by two independent reviewers, 14 longitudinal studies were included. Random-effects meta-analyses of studies involving a maximum total of 518 autistic and 3558 TD children and adolescents (mean baseline ages: 5.7-12.0 years) showed that ASD had significantly poorer EF than TD at both baseline and follow-up. However, there was no significant group difference in the age-related change in EF across domains, including working memory, inhibition, shifting, and planning. Robust Bayesian meta-analyses also provided substantial evidence in favor of the null hypothesis that ASD and TD groups showed similar changes over time for most EF processes. Limitations of the literature included the limited number of longitudinal studies and a narrow range of developmental stages and EF constructs analyzed across studies. Altogether, these findings suggest that autistic children and adolescents generally can improve in EF over time similarly to their neurotypical peers. This has important implications for parents and educators, encouraging appropriate EF training and intervention for autistic children and adolescents at an early stage.

Literature presents conflicting results on the pros and cons of pledget-reinforced sutures during surgical aortic valve replacement (SAVR). We aimed to investigate the effect of pledget-reinforced sutures versus sutures without pledgets during SAVR on different outcomes in a systematic review and meta-analysis.

A literature search was performed in five different medical literature databases. Studies must include patients undergoing SAVR and must compare any pledget-reinforced with any suturing technique without pledgets. The primary outcome was paravalvular leakage (PVL), and secondary outcomes comprised thromboembolism, endocarditis, mortality, mean pressure gradient (MPG) and effective orifice area (EOA). Results were pooled using a random-effects model as risk ratios (RRs) or mean differences (MDs) for which the no pledgets group served as reference.

Nine observational studies met the inclusion criteria. The risk of bias was critical in seven studies, and high and moderate in two other. The pooled RR for moderate or greater PVL was 0.59 (95 % confidence interval [CI] 0.13, 2.73). The pooled RR for mortality at 30-days was 1.02 (95 % CI 0.48, 2.18) and during follow-up was 1.15 (95 % CI 0.67, 2.00). For MPG and EOA at 1-year follow-up, the pooled MDs were 0.60 mmHg (95 % CI -4.92, 6.11) and -0.03 cm2 (95 % CI -0.18, 0.12), respectively.

Literature on the use of pledget-reinforced sutures during SAVR is at high risk of bias. Pooled results are inconclusive regarding superiority of either pledget-reinforced sutures or sutures without pledgets. Hence, there is no evidence to support or oppose the use of pledget-reinforced sutures.

Adverse neonatal outcomes following in utero antipsychotic exposure remain unclear. This systematic review and meta-analysis aimed to investigate associations between in utero first- and second-generation antipsychotic exposure and various neonatal outcomes. The primary outcome was small for gestational age. Secondary outcomes included other birth weight-related measures, prematurity and neonatal outcomes. MEDLINE, EMBASE, CENTRAL, ICTRP, and ClinicalTrials.gov were searched for on 8th July 2023. Two reviewers independently selected studies reporting associations between exposure and neonatal outcomes (all designs were eligible, no language or time restriction) and extracted data. ROBINS-I was used for risk of bias assessment. Meta-analyses were performed. Measures of association were odds ratios and mean differences. Thirty-one observational studies were included. Regarding small for gestational age < 10th percentile, meta-analysis was only performed for second-generation antipsychotics and showed no evidence for an association (OR 1.31 [95%CI 0.83; 2.07]; I²=46%; phet=0.13, n = 4 studies). First-generation antipsychotics were associated with an increased risk of small for gestational age < 3rd percentile (OR 1.37 [95%CI 1.02; 1.83]; I²=60%; phet=0.04, n = 5) and a lower mean birthweight (MD -135 g [95%CI -203; -66]; I²=53%; phet=0.07, n = 5). Second-generation antipsychotics were associated with large for gestational age > 97th percentile (OR 1.56 [95%CI 1.31; 1.87]; I²=4%; phet=0.37, n = 4) and Apgar score < 7 (OR 1.64 [95%CI 1.09; 2.47]; I²=47%; phet=0.13, n = 4). Both types of antipsychotics were associated with increased risks of preterm birth and neonatal hospitalization. Despite potential confounding in the studies, this systematic review and meta-analysis showed that newborns of mothers using antipsychotics during pregnancy are potentially at risk of adverse neonatal outcomes. Data sources: MEDLINE, EMBASE, CENTRAL, ICTRP, ClinicalTrials.gov. Prospero Registration Number CRD42023401805.