Credible Interval Research Articles

Adjunctive Fosfomycin for the Treatment of Staphylococcus aureus Bacteremia: A Pooled Post-hoc Analysis of Individual Participant Data from Two Randomized Trials.

The role of adjunctive fosfomycin in Staphylococcus aureus bacteremia (SAB) remains uncertain. We performed a post-hoc pooled analysis of individual participant data from the multicenter BACSARM and SAFO randomized controlled trials, which assessed fosfomycin combined with daptomycin or cloxacillin versus monotherapy for methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) SAB. The primary outcome was treatment success at 8 weeks, defined as the patient being alive, without signs of relapse, and showing resolution of fever and improvement in clinical signs and symptoms of infection. Secondary outcomes included persistent bacteremia at days 3 and 7, all-cause mortality at days 14, 30, and 60, and adverse events leading to treatment discontinuation. Bayesian and frequentist methods were used to estimate treatment effects, with the primary Bayesian analysis using a minimally informative prior centred on no treatment effect. This study is registered with ClinicalTrials.gov, NCT06695832. The intention-to-treat population comprised 369 participants, of whom 178 received fosfomycin combination therapy and 191 received monotherapy. The primary Bayesian analysis showed a 91.8% posterior probability that fosfomycin improves treatment success at 8 weeks (median relative risk [RR] 1.10, 95% credibility interval [Crl] 0.97-1.26) with sensitivity analyses (using pessimistic, sceptical, and optimistic priors) yielding probabilities between 75.8% and 97.2%. Fosfomycin was associated with a significant reduction in persistent bacteremia at day 3 (median RR 0.19, 95% CrI 0.07-0.41) and day 7 (median RR 0.22, 95% CrI 0.03-0.84). The adjusted frequentist analysis demonstrated an association between fosfomycin combination therapy and treatment success at 8 weeks (RR 1.04, 95% CI 1.02-1.06; p<0.001). Combination therapy was associated with a higher risk of adverse events (RR 2.03, 95% CI 1.13-3.63; p=0.017). Adjunctive fosfomycin may improve early bacterial clearance and treatment success in SAB but at the cost of increased toxicity.

Pharmacist-Led Education Intervention for Adults With Allergic Rhinitis: A Randomized Clinical Trial.

Allergic rhinitis (AR) affects 10% to 30% of the adult population globally. The current framework of pharmaceutical care for managing AR focuses on community pharmacies, with limited structured pharmaceutical care in public health care settings. To evaluate the effectiveness of a pharmacist-led education intervention (AR-PRISE) in a public health care institution compared with standard care for managing AR among adults. This randomized clinical trial used a 2-arm, parallel-group, open-label design in the otorhinolaryngology clinic of a government-funded tertiary referral hospital in northern Malaysia. Enrollment occurred from June 1, 2023, to February 15, 2024, with follow-up completed August 6, 2024. The trial included Malaysian patients aged 18 to 80 years who had received a diagnosis of AR and were able to comprehend English or Malay. Of the 209 screened patients, 154 were recruited and randomly assigned into intervention and control groups, with 149 completing the study. The AR-PRISE intervention involved an 8-minute educational video on AR and structured pharmacist counseling. The primary outcomes were between-group differences at day 180 in knowledge level, symptom control (Total Nasal Symptom Score [TNSS] for the past 12 hours and past 2 weeks), medication adherence (number of days of intranasal corticosteroid use), and quality of life (assessed by the European Quality of Life 5-Dimension 5-Level Instrument and European Quality of Life Visual Analog Scale). Assessments were conducted at baseline and days 60 (±7), 120 (±7), and 180 (±7). All analyses were performed on an intention-to-treat basis. Among the 154 participants, the mean (SD) age was 46.5 (17.0) years, and 97 (63.0%) were women; 77 participants were randomized to each group. In the intention-to-treat analysis, the intervention group showed statistically significant improvement in TNSSs for the past 2 weeks compared with controls (estimate [SE], 0.14 [0.06]; 95% credible interval [CrI], 0.03-0.25). Significant reductions in the TNSS for the past 2 weeks were observed at all time points (day 60: estimate [SE], 0.18 [0.05]; 95% CrI, 0.08-0.28; day 120: estimate [SE], 0.21 [0.05]; 95% CrI, 0.11-0.31; and day 180: estimate [SE], 0.11 [0.05]; 95% CrI, 0.01-0.21). No significant differences were observed for knowledge level, TNSS for the past 12 hours, medication adherence, or quality of life. In this randomized clinical trial, the AR-PRISE intervention significantly improved AR symptom control (TNSS for the past 2 weeks) compared with standard care over 180 days but did not show significant effects on other coprimary outcomes (AR knowledge, TNSS for the past 12 hours, medication adherence, or quality of life). These findings suggest that while pharmacist-led education can enhance symptom management, additional strategies may be needed to address broader aspects of AR care. ClinicalTrials.gov Identifier: NCT06027736.

Vaporized Nicotine Products for Smoking Cessation Among People Experiencing Social Disadvantage : A Randomized Clinical Trial.

Vaporized nicotine products (VNPs) are more effective than nicotine replacement therapy (NRT) for smoking cessation in general populations, but their effectiveness among low socioeconomic groups is largely unknown. To examine whether VNPs are more effective than NRT for smoking cessation among people experiencing social disadvantage. Two-group, open-label, randomized trial with blinded outcome ascertainment. (Australian New Zealand Clinical Trials Registry ACTRN12621000076875). Australia, between March 2021 and December 2022. 1045 adults who smoked daily, were willing to quit smoking, and were receiving a government pension/allowance (proxy for social disadvantage). Participants were randomly assigned (1:1) to either a free 8-week supply of NRT or VNPs, and all participants received text-message support. The primary outcome was 6-month continuous smoking abstinence verified using a carbon monoxide breath test at 7-month follow-up. Analysis included randomly assigned participants in accordance with Russell Standard criteria and the intention-to-treat principle. Among 1045 randomly assigned participants, 866 (82.9%) completed final follow-up. The verified 6-month continuous abstinence rate was 9.6% (50 of 523) in the NRT group and 28.4% (148 of 522) in the VNP group (posterior risk difference estimate, 18.7% [95% credible interval, 14.1% to 23.3%]; >99% posterior probability that VNP is superior). Self-reported adverse events occurred less frequently in the VNP group (355 events among 237 participants) compared with the NRT group (442 events among 278 participants; incident rate ratio, 0.75 [95% CI, 0.65 to 0.88]; P < 0.001). Biochemical verification method tested short-term exposure to cigarette smoke. Findings indicate that VNPs were more effective than NRT for smoking cessation in this population. Given the challenges for cessation among these socially disadvantaged populations, VNPs present a promising treatment option for this priority group. Australian National Health and Medical Research Council.

Systemic evaluation of inclisiran on the risk of new-onset diabetes and hyperglycemia compared to evolocumab and atorvastatin

BackgroundInclisiran is an siRNA-based cholesterol-lowering drug with N-acetylgalactosamine carbohydrate (GalNAc) and is used for the treatment of hypercholesterolemia or dyslipidemia. It reduces LDL-C by 50%, with a convenient dosing schedule and fewer adverse events. Unlike statins, inclisiran has not been associated with an increased risk of muscle or liver adverse events in clinical studies. This favorable safety profile makes inclisiran a valuable alternative for patients who are intolerant of statins due to muscle or hepatic side effects. However, its impact on glycemic control and diabetes risk is unclear and understudied.Methods and resultsThe US Food and Drug Administration Adverse Event Reporting System (FAERS) study analyzed hyperglycemia and diabetes risks for inclisiran, atorvastatin, and evolocumab. Data from 2021 to 2024 were assessed for Medical Dictionary (MedDRA) terms, and SAS 9.4 with a reporting advantage ratio (ROR) and Bayesian credible interval progressive neural network (BCPNN) was used for analysis. Systematic review and meta-analysis were conducted using PubMed, Embase, and specific search terms. Two research workers extracted data independently, and the study quality was assessed with the Cochrane and Newcastle–Ottawa scales. RevMan 5.4 and Stata 18.0 were used for analyses. Ethical approval was waived due to the use of public, anonymous data. From 2015 Q1 to 2024 Q1, 12,821,285 adverse events were reported in FEARS, with 3,375 inclisiran, 126,620 evolocumab, and 42,228 atorvastatin cases. Atorvastatin had a higher ROR for type 2 diabetes (195.03) than inclisiran (0.95) and evolocumab, but it was not statistically significant. Glucose intolerance and blood glucose issues showed weak signals for inclisiran and atorvastatin. A literature search yielded 16 relevant articles, including six cohort studies and 10 RCTs, totaling 297,863 patients. The incidence of new-onset diabetes was higher with atorvastatin than with inclisiran, placebo, and evolocumab. The SUCRA rankings were atorvastatin &amp;gt; inclisiran &amp;gt; placebo &amp;gt; evolocumab for new diabetes incidence.ConclusionThe FAERS study and meta-analysis indicate that inclisiran may carry a lower risk of new-onset diabetes than atorvastatin, warranting further investigation into inclisiran’s impact on glycemic control.

Atomistic-Based Fatigue Property Normalization Through Maximum A Posteriori Optimization in Additive Manufacturing

This work presents a multiscale, microstructure-aware framework for predicting fatigue strength distributions in additively manufactured (AM) alloys—specifically, laser powder bed fusion (L-PBF) AlSi10Mg and Ti-6Al-4V—by integrating density functional theory (DFT), instrumented indentation, and Bayesian inference. The methodology leverages principles common to all 3D printing (additive manufacturing) processes: layer-wise material deposition, process-induced defect formation (such as porosity and residual stress), and microstructural tailoring through parameter control, which collectively differentiate AM from conventional manufacturing. By linking DFT-derived cohesive energies with indentation-based modulus measurements and a MAP-based statistical model, we quantify the effect of additive-manufactured microstructural heterogeneity on fatigue performance. Quantitative validation demonstrates that the predicted fatigue strength distributions agree with experimental high-cycle and very-high-cycle fatigue (HCF/VHCF) data, with posterior modes and 95 % credible intervals of σ^fAlSi10Mg=86−7+8MPa and σ^fTi–6Al–4V=115−9+10MPa, respectively. The resulting Woehler (S–N) curves and Paris crack-growth parameters envelop more than 92 % of the measured coupon data, confirming both accuracy and robustness. Furthermore, global sensitivity analysis reveals that volumetric porosity and residual stress account for over 70 % of the fatigue strength variance, highlighting the central role of process–structure relationships unique to AM. The presented framework thus provides a predictive, physically interpretable, and data-efficient pathway for microstructure-informed fatigue design in additively manufactured metals, and is readily extensible to other AM alloys and process variants.

Metformin and Time to Sustained Recovery in Adults With COVID-19: The ACTIV-6 Randomized Clinical Trial.

The effect of metformin on reducing symptom duration among outpatient adults with COVID-19 has not been studied. To assess metformin compared with placebo for symptom resolution during acute infection with SARS-CoV-2. The Accelerating COVID-19 Therapeutic Interventions and Vaccines platform evaluated repurposed medications for mild to moderate COVID-19. Between September 19, 2023, and May 1, 2024, participants 30 years or older with confirmed SARS-CoV-2 infection and 2 or more COVID-19 symptoms for 7 days or less were included at 90 US sites. Participants were randomized to receive metformin (titrated to 1500 mg, daily) or placebo for 14 days. The primary outcome was time to sustained recovery (3 consecutive days without COVID-19 symptoms) within 28 days of receiving the study drug. Secondary outcomes included time to clinic visit, emergency department (ED) visit, hospitalization, or death. Safety events of interest were hypoglycemia and lactic acidosis. Among 2991 participants who were randomized and received study drug, the median age was 47 (IQR, 38-58) years; 1895 (63.4%) were female, 25 (0.8%) were American Indian of Alaska Native, 77 (2.6%) were Asian, 350 (11.7%) were Black, African American, or African, 1392 (46.5%) identified as Hispanic or Latino, 8 (0.3%) were Native Hawaiian or other Pacific Islander, 2395 (80.1%) were White, and 2044 (68.3%) reported 2 or more doses of a SARS-CoV-2 vaccine. Among 1443 (48.2%) participants who received metformin and 1548 (51.8%) who received placebo, differences in time to sustained recovery were not observed (adjusted hazard ratio, 0.96; 95% credible interval [CrI], 0.89-1.03; P for efficacy = .11). The median time to sustained recovery was 9 days (95% CI, 9-10) for metformin and 10 days (95% CI, 9-10) for placebo. No deaths were reported; 103 participants reported clinic visits, ED visits, or hospitalization: 54 in the metformin group and 49 in the placebo group (hazard ratio, 1.25; 95% CrI, 0.82-1.78; P for efficacy = .13). Overall, 35 (1.2%) reported ED visits or hospitalization (1.1% in the metformin and 1.3% in the placebo group). Seven participants who received metformin and 3 who received placebo experienced a serious adverse event over 180 days. There were 4 episodes of participant-reported hypoglycemia in the placebo group and 2 in the metformin group. In this randomized clinical trial, metformin was not shown to shorten the time to symptom resolution in low-risk adults with COVID-19. The median days to symptom resolution was numerically but not significantly lower for metformin. Safety was not a limitation in the study population. ClinicalTrials.gov Identifier: NCT04885530.

A novel Bayesian approach based on wing geometric morphometry to discriminate Culicoides species (Diptera: Ceratopogonidae)

Abstract A Bayesian Procrustes analysis (BPA) was used to discriminate livestock-associated species: Culicoides innoxius Sen and Das Gupta, Culicoides peregrinus Kieffer, and Culicoides oxystoma Kieffer. BPA results were compared with classical geometric morphometric analysis (CGMA). Markov Chain Monte Carlo (MCMC) parameters, Kullback-Leibler (KL) divergence, Hellinger distance, and total variation distance were considered. BPA validation was further done using CGMA. BPA depicted significant differences at 95% credible intervals (CrIs) in their posterior distribution of Procrustes variance (σ) between the species with minimum overlap between closely related ones, C. innoxius and C. peregrinus, and no overlap between distantly related C. oxystoma and C. peregrinus; C. innoxius. MCMC posterior convergence plots supported the accuracy of the BPA. In the trace plots, the MCMC explored the parameter space effectively. For the estimation of divergence between the distribution of species, KL divergence, Hellinger distance, and total variance distance were calculated, which exhibited the highest dissimilarity between C. oxystoma and C. innoxius, followed by C. oxystoma and C. peregrinus and the lowest was between C. peregrinus and C. innoxius. The effectiveness of the BPA over CGMA was assessed by incorporating Culicoides regalis individuals within the analysis. In BPA, an erratic convergence plot indicated the presence of C. regalis within the C. innoxius dataset, whereas CGMA could not separate C. regalis. This is probably the first time the Bayesian approach has been used in Culicoides taxonomy. So far, the results have yielded reliable, sensitive, and accurate species identification.

Randomized Phase 2 Trial of Presurgical Androgen Deprivation Therapy With or Without Axitinib in Prostate Cancer Presenting With Lymph Node Metastasis.

Randomized Phase 2 Trial of Presurgical Androgen Deprivation Therapy With or Without Axitinib in Prostate Cancer Presenting With Lymph Node Metastasis.

Universal cervical-length screening to prevent preterm birth in twin pregnancy: cost-utility analysis.

The purpose of this cost-utility analysis was to model the clinical and economic impact of three cervical-length screening strategies among low-risk twin pregnancies: two-step universal screening (at 18-20 and 20-22 weeks), one-step universal screening (at 18-20 weeks) and no screening. This study used a decision-analytic model (decision tree and cohort state transition model) with a 100-year time horizon in a Canadian context. The population included dichorionic diamniotic twin pregnancies without a history of preterm birth or prophylactic progesterone or cerclage. The model assumed that vaginal progesterone was initiated for cervical length ≤ 25 mm and that cervical cerclage was performed plus vaginal progesterone treatment for cervical length ≤ 15mm. The primary outcomes were total lifetime health-related costs (in 2023 Canadian dollars ($)), quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios. Clinical outcomes included the probability of preterm birth (≤ 28 and ≤ 34 weeks), probability of stillbirth and life expectancy. Probabilistic and deterministic sensitivity analyses were carried out. Base-case and probabilistic sensitivity analysis showed that, when compared with no screening, the two-step screening strategy increased the QALYs modestly (0.62 (95% credible interval (CrI), -0.16 to 1.41)) and decreased lifetime costs (-$2460 (95% CrI, -$4850 to $251)) by reducing the rate of preterm birth. The one-step screening strategy, although inferior to the two-step screening strategy, also increased the QALYs and reduced costs. Findings consistent with these were obtained on testing of the model assumptions with deterministic sensitivity analysis. This cost-utility analysis supports a universal two-step screening strategy for twin pregnancies in a Canadian context. Although the conclusions of this analysis are robust in terms of the sensitivity analysis, more reliable predictions of long-term costs and quality of life require more twin-specific lifetime data. Additionally, cost-utility analyses in other healthcare contexts are needed. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Dipeptidyl Peptidase-4 Inhibitors and the Risk of Fractures in Type 2 Diabetes Mellitus Patients: A Bayesian Network Meta-Analysis.

Type 2 diabetes mellitus (T2DM) increases the risk of fractures and its effects on bone health. The impact of dipeptidyl peptidase-4 inhibitors (DPP-4i) on bone fracture risk is unclear. We performed a network meta-analysis (NMA) to assess the impact of DPP-4i on fracture risk in patients with T2DM. A comprehensive systematic literature search was conducted on PubMed/Medline, Cochrane Library, and ClinicalTrials.gov until June 2024 to identify RCTs reporting fracture events with DPP-4i among T2DM patients. A Bayesian NMA has been performed to calculate the odds ratio (OR) and 95% credible intervals (CrI). Surface under the cumulative ranking analysis (SUCRA) was utilized to assess the rank probability of DPP-4i. A total of 85 RCTs were identified, including 89,965 T2DM patients with 1,083 fracture events. In the direct meta-analysis, DPP-4i did not elevate fracture risk compared to placebo or other oral anti-diabetics (OADs) (OR (95%CI): 1.04 (0.91-1.18); p=0.57 and 1.18 (0.79-1.74); p=0.96, respectively). Alogliptin and sitagliptin indicated a non-significant trend towards reducing fracture risk compared to placebo (OR (95%CI): 0.59 (0.31-1.15); p=0.12) and OADs (OR (95%CI): 0.73 (0.41-1.30); p=0.28), respectively. In the NMA, alogliptin significantly reduced fracture risk compared to linagliptin and SGLT2i (OR (95%CrI): 0.41 (0.16-0.93) and 0.16 (0.017-0.83), respectively). Conversely, linagliptin increased fracture risk compared to sulfonylurea (OR (95%CrI): 2.3 (1.1-5.2)). According to SUCRA, alogliptin (84%) ranked as the preferred treatment for reducing fracture risk in T2DM patients. Overall, DPP-4i was not associated with an increased risk of fractures in patients with T2DM. However, alogliptin demonstrated a reduced risk of fractures when compared to both linagliptin and SGLT2i. Further long-term clinical studies are needed to confirm the present findings.

Higher fat-soluble vitamin and phosphorus intake are associated with less dental caries among children and adolescents in the United States, NHANES 2011–2018

IntroductionHistoric research shows that a diet rich in calcium, phosphorus, fat-soluble vitamins, and vitamin C, and low in phytates may help to prevent and arrest dental caries; however, current research on this topic is scarce. We examined associations of dietary intake of these nutrients with dental caries prevalence in the United States among youth 1–19 years old.MethodsThe study included 2,676 young children (1–5 years), 3,214 older children (6–11 years) and 3,701 adolescents (12–19 years) from the National Health and Nutrition Examination Survey (NHANES 2011–2018). Daily nutrient intake was ascertained via two 24 h recalls. We assessed the number and presence (yes/no) of decayed and/or filled teeth (DFT) among young children and decayed, missing and/or filled teeth (DMFT) among older children and adolescents. Covariate-adjusted survey-weighted negative binomial regression was used to examine associations of nutrient quartiles with DFT or DMFT scores. We examined joint associations of nutrients with the probability of caries using the probit extension of Bayesian Kernel Machine Regression.ResultsMean (SD) DFT or DMFT scores were 0.82 (2.23) for young children, 2.08 (2.81) for older children and 2.51 (3.35) for adolescents. Higher phosphorus and vitamin A intake was associated with fewer DFT among young children [incident rate ratio (IRR) = 0.52, 95% CI: 0.29–0.94, p = 0.03, and IRR = 0.60, 95% CI: 0.37–0.95, p = 0.03, respectively]. Unexpectedly, higher intake of phytates was also associated with lower DFT scores among young children (IRR = 0.37, 95% CI: 0.21–0.65, p = 0.001). Higher phosphorus and vitamin E intake was associated with fewer DMFT among older children (IRR = 0.58, 95% CI: 0.40–0.84, p = 0.003 and IRR = 0.73, 95% CI: 0.54–0.97, p = 0.03, respectively). For adolescents, higher phosphorus and vitamin K intake was associated with fewer DMFT (IRR = 0.72, 95% CI: 0.53–0.99, p &amp;lt; 0.05; IRR = 0.82, 95% CI: 0.68–0.97, p = 0.02, respectively). The joint effect of nutrients was also associated with lower odds of DMFT. Setting all nutrients at their 75th relative to 50th percentiles was associated with 0.87 [95% credible interval (CrI): 0.81, 0.94] and 0.92 (95% CrI: 0.85, 0.99) lower odds of DMFT in older children and adolescents, respectively. Phosphorus and vitamin K contributed most to these associations.ConclusionFat-soluble vitamins and phosphorus may have systemic dental benefits that warrant further investigation.

Cost Savings of Switching to Aspirin for Thromboprophylaxis in Orthopaedic Trauma Patients: A Budget Impact Analysis.

Clinical guidelines recommend low-molecular-weight heparin (enoxaparin) to prevent venous thromboembolism in orthopaedic trauma patients. However, a large trial recently found aspirin noninferior to enoxaparin in preventing death and pulmonary embolism in this population. We modeled cost implications for the United States healthcare system if aspirin replaced enoxaparin as the standard of care for thromboprophylaxis in orthopaedic trauma patients. The modeling compared spending under two scenarios: continued use of enoxaparin versus switching to aspirin. The model included fracture incidence estimates from the National Inpatient Sample and dose and duration data from the clinical trial. We derived medication costs from current market prices across payer types and care settings (ie, inpatient and postdischarge prescriptions). The model incorporates uncertainty around each parameter based on calculated standard errors and generates bootstrapped estimates of costs and cost savings disaggregated by the payer. The results indicated that prescribing enoxaparin for thromboprophylaxis to more than 600,000 fracture patients costs $162.7 million annually, whereas thromboprophylaxis with aspirin would cost $1.6 million annually. Spending on thromboembolic events totals $210.7 million under the enoxaparin scenario and $222.1 million with aspirin. Overall, aspirin for thromboprophylaxis in fracture patients would yield annual savings of $149.7 million (95% credible interval: $97 to $208 million) compared with enoxaparin. Our findings suggest that a widespread switch from enoxaparin thromboprophylaxis to aspirin would lead to more than $100 million in annual cost savings in the United States alone. Insurers stand to benefit most from this practice change. However, patients, especially those without insurance, would realize considerable savings from aspirin thromboprophylaxis. Level 1, Economic.

Estimation of System Reliability Based on Inverted Exponentiated Pareto Distribution Under a Progressively First‐Failure Censored Scheme With Application

ABSTRACTThis article explores and derives the estimation of the multicomponent stress–strength (MSS) reliability parameter, assuming that the samples are coming from the inverted exponentiated Pareto distribution using a progressively first‐failure censored scheme. To estimate the MSS reliability, both classical and Bayesian approaches are adopted. In the classical approach, the maximum likelihood and the asymptotic confidence interval estimation methods are used. The Bayes estimates with their corresponding highest posterior density credible interval estimates are obtained under the Bayesian approach, under the linear exponential loss function under both the noninformative and gamma informative priors. In addition, to compute the Bayes estimates, Markov chain Monte Carlo methods are used. To compare the efficacy of the different estimation strategies adopted in this paper, a Monte Carlo simulation study is carried out. To demonstrate the applicability of the proposed methodology, two real‐life scenarios resulting/arising from two different carbon fiber data sets are re‐analyzed.

Comparison of mortality and cardiovascular morbidity following treatment for hyperthyroidism: A systematic review and bayesian network meta-analysis.

Therapeutic approaches for hyperthyroidism, namely antithyroid drugs, radioiodine, and thyroidectomy, aim to restore normal thyroid function while minimizing harm. However, the difference in outcomes related to mortality and cardiovascular diseases between them remains controversial. PubMed, Embase, Cochrane Central, and Web of Science were searched for randomized controlled trials and cohort studies that compared any of the three supracited therapeutic approaches between themselves. A Bayesian model estimated hazard ratios (HR) with 95% credible intervals (CrI) using a random-effects model. Treatments were ranked by surface under the cumulative ranking curve (SUCRA). Eight cohort studies encompassing 172,585 hyperthyroid patients were included. Thyroidectomy was associated with lower all-cause mortality compared to antithyroid drugs (HR 0.442; 95% CrI 0.244-0.783) but not radioiodine (HR 0.675; 95% CrI 0.424-1.296). No significant differences were observed for cardiovascular mortality when comparing thyroidectomy to antithyroids (HR 0.440; 95% CrI 0.177-1.127) and radioiodine (HR 0.580; 95% CrI 0.342-1.064). For major cardiovascular events (MACE) there was no significant difference between radioiodine vs. antithyroids (HR 0.557; 95% CrI 0.265-1.006) and thyroidectomy (HR 0.784; 95% CrI 0.347-1.917). Thyroidectomy did not reduce heart failure risk vs. antithyroids (HR 0.353; 95% CrI 0.115-1.251) and radioiodine (HR 0.426; 95% CrI 0.131-1.749). SUCRA rankings suggested thyroidectomy as the best treatment concerning mortality and heart failure, while radioiodine ranked highest for MACE. Thyroidectomy and radioiodine may offer better long-term cardiovascular and mortality outcomes compared to antithyroid drugs. Further studies with proper designs are needed to verify the nature of these associations.

Comparative Efficacy of Exercise Versus Passive Physical Therapy in Improving Non-Specific Neck Pain: A Multilevel Network Meta-Analysis and Dose-Response Analysis.

Comparative Efficacy of Exercise Versus Passive Physical Therapy in Improving Non-Specific Neck Pain: A Multilevel Network Meta-Analysis and Dose-Response Analysis.

Optimal Tai Chi dose for improving anxiety, depression, and sleep quality in older adults: A Bayesian meta-analysis

Objective As the population ages, an increasing proportion of older adults experience mental health problems. Although Tai Chi ameliorates these negative outcomes, the required dosage remains unknown. This study aimed to determine the optimal dose of Tai Chi to improve anxiety, depressive symptoms, and sleep quality. Data sources A systematic search using MEDLINE, Embase, Cochrane Library, and Web of Science was conducted from the beginning of the respective database information until June 5, 2025. Review methods A pairwise and dose-response meta-analysis using Bayesian hierarchical random-effects models to analyse the effects of a Tai Chi intervention on anxiety, depression, and sleep quality in older adults. In addition, the quality of the literature was assessed using the Cochrane Risk of Bias Tool 2. Results A total of 2843 older adults were enrolled in 37 randomised controlled trials, including 1424 (50.1%) in the Tai Chi group. Tai Chi intervention improved anxiety (standardized mean difference (SMD) : −0.47, 95% credible interval (CrI): −0.65 to −0.30), depressive symptoms (SMD: −0.41, 95% CrI: −0.50 to −0.33). However, while Tai Chi improved sleep quality in older adults, the effect, though statistically significant, was small in magnitude (SMD: −0.12, 95% CrI: −0.20 to −0.04), with large heterogeneity. Conclusion Tai Chi is an effective intervention for improving mental health and sleep in older adults, with dose-dependent benefits. Our findings establish an optimal therapeutic target of 500-700 MET-minutes/week, transforming Tai Chi from a general recommendation into a specific, evidence-based prescription for clinical practice.

Influence of bodyweight on prednisolone pharmacokinetics in dogs

BackgroundLarger dogs may be at greater risk of prednisolone side effects, yet there is limited research about how bodyweight affects prednisolone pharmacokinetics in dogs.Hypothesis/objectivesTo describe the relationship between prednisolone dose, bodyweight, body surface area (BSA) and prednisolone area under the curve (AUC) in dogs receiving prednisolone for medical reasons.Animals25 client owned dogs receiving prednisolone for medical reasons.MethodsObservational population pharmacokinetic study. Liquid chromatography tandem mass spectrometry was used for plasma prednisolone quantification. Data analysis was conducted in a two-stage approach using non-compartmental modelling. A Bayesian non-linear regression model described the relationship between AUC over 8 hours (ng·min/mL), bodyweight and prednisolone dose.ResultsFrom the allometric scaling model of the form AUC8h = A · BW B, the scaling exponent was.83 (90% credible interval (CrI):.60–1.06) and the coefficient was 22.8 (90% CrI: 11.8–43.4). This model suggests that equivalent exposure would be obtained using an intermediate strategy between BSA and bodyweight dosing, but the total evidence provided was relatively weak.Conclusions and clinical importanceEvidence was obtained regarding the nonlinear relationship between prednisolone pharmacokinetics and bodyweight in dogs; however, this model is currently too imprecise for clinical dose determination.

Network meta-analysis of the prevalence and antimicrobial resistance of Escherichia coli isolated from bovine milk and dairy products: A global perspective.

Network meta-analysis of the prevalence and antimicrobial resistance of Escherichia coli isolated from bovine milk and dairy products: A global perspective.

A systematic review and network meta-analysis of preservation techniques of donor kidneys.

A systematic review and network meta-analysis of preservation techniques of donor kidneys.

Effects of different respiratory training methods on respiratory function in patients with spinal cord injury: a network meta-analysis of randomized controlled trials

ObjectiveThis network meta-analysis (NMA) compared the efficacy of various respiratory training methods in improving respiratory function in patients with spinal cord injury (SCI).MethodsRandomized controlled trials (RCTs) on respiratory training interventions for SCI patients were searched in PubMed, Embase, Web of Science, and the Cochrane Library through September 1, 2024. The risk of bias in the included studies was assessed using the Cochrane tool. Review Manager 5.4 was used to conduct a systematic review using Bayesian NMA methods. The Confidence in Network Meta-Analysis (CINeMA) framework was employed to evaluate the quality of evidence. The primary outcomes were maximal inspiratory pressure (MIP), forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC).ResultsSeventeen RCTs (n = 625) were included, evaluating eight respiratory training interventions and one control intervention. NMA revealed that for improving MIP, transcutaneous spinal cord stimulation plus resistance respiratory muscle training (tSCS_RRMT) (SUCRA 86.32%) showed the greatest efficacy, followed by resistance respiratory muscle training (RRMT) (SUCRA 84.09%). For FEV1, repetitive functional magnetic stimulation combined with abdominal neuromuscular electrical stimulation and routine breathing training (rFMS_NMES_RBT) (SUCRA 89.41%) demonstrated superior efficacy, followed by incentive spirometry combined with the abdominal drawing-in maneuver (IS_ADIM) (SUCRA 70.05%). For FVC, IS_ADIM (SUCRA 76.25%) was most effective, followed by routine breathing training (RBT) (SUCRA 65.40%). League table results indicated that RRMT (mean difference (MD) 13.25, 95% credible intervals (CrI) [7.51, 18.92]) significantly improved MIP compared to the control intervention; IS_ADIM (MD 0.58, 95% CrI [0.31, 0.85]) and RBT (MD 0.49, 95% CrI [0.29, 0.69]) enhanced FVC compared to the control intervention.ConclusiontSCS_RRMT appears to be the most effective for improving MIP, rFMS_NMES_RBT for enhancing FEV1, and IS_ADIM for improving FVC based on SUCRA rankings. Due to irreconcilable heterogeneity, indirectness, imprecision, and incoherence, the reliability of the evidence is limited.Trial registration: This network meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was prospectively registered in PROSPERO (CRD42024592511).