Evaluating recommendation-based dietary and physical activity strategies for prostate cancer prevention: a target trial emulation in the Health Professionals Follow-up Study.

The 2018 World Cancer Research Fund/American Institute for Cancer Research recommends sustained strategies of physical activity and diet for cancer prevention, but evidence for long-term prostate cancer risk is limited. Using observational data from 27,859 men in the Health Professionals Follow-up Study, we emulated a target trial of recommendation-based physical activity and dietary strategies and 26-year risks of prostate cancer, adjusting for risk factors via the parametric g-formula. Compared with no intervention, limiting sugar-sweetened beverages showed a 0.4% (0.0-0.9%) lower risk of lethal (metastatic or fatal) disease and 0.5% (0.1-0.9%) lower risk of fatal disease. Restricting consumption of processed foods showed a 0.4-0.9% higher risk of all prostate cancer outcomes. Estimated risk differences for clinically significant disease were close to null for strategies involving fruits and non-starchy vegetables, whole grains and legumes, red meat, and processed meat, as well as under a joint strategy of physical activity and diet. Compared with a "low adherence" strategy, maintaining recommended physical activity levels showed a 0.4% (0.1-0.8%) lower risk of lethal and 0.5% (0.2-0.8%) lower risk of fatal disease. Adhering to specific components of current physical activity and dietary recommendations may help to prevent lethal and fatal prostate cancer over 26 years.

The effect of treatment timing on repeat revascularization in patients with stable ischemic heart disease.

Objectives: In patients with stable ischemic heart disease, there is no evidence for the effect of revascularization treatment timing on the need for repeat procedures. We aimed to determine if repeat revascularizations differed among patients who received coronary artery bypass graft surgery after the time recommended by physicians compared with those who had timely percutaneous coronary intervention. Methods: We identified 25,520 British Columbia residents 60 years or older who underwent first-time nonemergency revascularization for angiographically proven, stable left main or multivessel ischemic heart disease between January 1, 2001, and December 31, 2016. We estimated unadjusted and adjusted cumulative incidence functions for repeat revascularization, in the presence of death as a competing risk, after index revascularization or last staged percutaneous coronary intervention for patients undergoing delayed coronary artery bypass grafting compared with timely percutaneous coronary intervention. Results: After adjustment with inverse probability of treatment weights, at 3 years, patients who underwent delayed coronary artery bypass grafting had a statistically significant lower cumulative incidence of a repeat revascularization compared with patients who received timely percutaneous coronary intervention (4.84% delayed coronary artery bypass grafting, 12.32% timely percutaneous coronary intervention; subdistribution hazard ratio, 0.16, 95% CI, 0.04-0.65). Conclusions: Patients who undergo delayed coronary artery bypass grafting have a lower cumulative incidence of repeat revascularization than patients who undergo timely percutaneous coronary intervention. Patients who want to wait to receive coronary artery bypass grafting will see the benefit of lower repeat revascularization over percutaneous coronary intervention unaffected by a delay in treatment.

Aspirin 162 mg versus 81 mg for Preeclampsia Prophylaxis in High-risk Obese Individuals: A Comparative Effectiveness Open Label Randomized Trial (ASPREO).

BACKGROUND: In the United States, leading medical societies recommend 81 mg of aspirin daily for the prevention of preeclampsia (PE) in women at risk, whereas the NICE guidelines in the UK recommend a dose as high as 150 mg of aspirin. Recent data also suggest that in the obese population, inadequate dosing or aspirin resistance may impact the efficacy of aspirin at the currently recommend doses. OBJECTIVE: We evaluated whether daily administration of 162 mg aspirin would be more effective compared to 81 mg in decreasing the rate of PE with severe features in high-risk obese pregnant individuals. STUDY DESIGN: We performed a randomized trial between May 2019 and November 2022. Individuals at 12 to 20-weeks gestational age (GA) with a BMI ≥ 30 kg/m2 at time to enrollment, and at least one of three high risk factors: history of PE in a prior pregnancy, at least stage I hypertension documented in the index pregnancy, pre-gestational diabetes or gestational diabetes diagnosed prior to 20 weeks GA were randomized to either 162 mg or 81 mg of aspirin daily till delivery, participants were not blinded to treatment allocation. Exclusion criteria were: multifetal gestation, known major fetal anomalies, seizure disorder, baseline proteinuria, on aspirin due to other indications, or contraindication to aspirin. The primary outcome was PE with severe features (PE or superimposed PE with severe features, eclampsia, or HELLP). Secondary outcomes included rates of preterm birth due to PE, small for gestational age (SGA), postpartum hemorrhage, abruption, and medication side effects. A sample size of 220 was needed using a preplanned Bayesian analysis of the primary outcome to estimate the posterior probability of benefit or harm with a neutral informative prior. RESULTS: Of 343 eligible individuals, 220 (64.1%) were randomized. The primary outcome was available for 209/220 (95%). Baseline characteristics were similar between groups, median gestational age at enrollment was 15.9 weeks in the 162 mg aspirin group and 15.6 weeks in the 81 mg aspirin group. Enrollment prior to 16 weeks occurred in 55/110 of those assigned to 162 mg and 58/110 of those assigned to 81 mg of aspirin. The primary outcome occurred in 35% in the 162 mg aspirin group and in 40% in the 81 mg aspirin group (posterior relative risk, 0.88; 95% credible interval, 0.64-1.22). Bayesian analysis indicated a 78% probability of a reduction in the primary outcome with 162 mg aspirin compared to 81 mg aspirin dose. Rates of indicated preterm birth due to preeclampsia (21% vs 21%), SGA (6.5% vs 2.9%), abruption (2.8% vs 3.0%) and postpartum hemorrhage (10% vs 8.8%) were similar between groups. Medication adverse effects were also similar. CONCLUSION: Among high-risk obese individuals, there was 78% probability of benefit that 162 mg aspirin compared to 81 mg will decrease the rate of PE with severe features. With a best estimate of a 12% reduction when using 162 mg of aspirin in comparison to 81 mg of aspirin in this population. This trial supports doing a larger multicenter trial.

Examining external control arms in oncology: A scoping review of applications to date.

OBJECTIVES: Randomized controlled trials (RCTs) are the gold standard for evaluating the comparative efficacy and safety of new cancer therapies. However, enrolling patients in control arms of clinical trials can be challenging for rare cancers, particularly in the context of precision oncology and targeted therapies. External Control Arms (ECAs) are a potential solution to address these challenges in clinical research design. We conducted a scoping review to explore the use of ECAs in oncology. METHODS: We systematically searched four databases, namely MEDLINE, EMBASE, Web of Science, and Scopus. We screened titles, abstracts, and full texts for eligible articles focusing on patients undergoing therapy for cancer, employing ECAs, and reporting clinical outcomes. RESULTS: Of the 629 articles screened, 23 were included in this review. The earliest included studies were published in 1996, while most studies were published in the past 5 years. 44% (10/23) of ECAs were employed in blood-related cancer studies. Geographically, 30% (7/23) of studies were conducted in the United States, 22% (5/23) in Japan, and 9% (2/23) in South Korea. The primary data sources used to construct the ECAs involved pooled data from previous trials (35%, 8/23), administrative health databases (17%, 4/23) and electronic medical records (17%, 4/23). While 52% (12/23) of the studies employed methods to align treatment and ECAs characteristics, 48% (11/23) lacked explicit strategies. CONCLUSION: ECAs offer a valuable approach in oncology research, particularly when alternative designs are not feasible. However, careful methodological planning and detailed reporting are essential for meaningful and reliable results.

Sodium-glucose cotransporter-2 inhibitors and incidence of atrial fibrillation in older adults with type 2 diabetes: a retrospective cohort analysis.

Objectives: To investigate the risk of atrial fibrillation (AF) with sodium-glucose cotransporter-2 inhibitors (SGLT2is) compared to dipeptidyl peptidase-4 inhibitor (DPP4i) use in older US adults and across diverse subgroups. Methods: We conducted a retrospective cohort analysis using claims data from 15% random samples of Medicare fee-for-service beneficiaries. Patients were adults with type 2 diabetes (T2D), no preexisting AF, and were newly initiated on SGLT2i or DPP4i. The outcome was the first incident AF. Inverse probability treatment weighting (IPTW) was used to balance the baseline covariates between the treatment groups including sociodemographics, comorbidities, and co-medications. Cox regression models were used to assess the effect of SGLT2i compared to DPP4i on incident AF. Results: Of the 97,436 eligible individuals (mean age 71.2 ± 9.8 years, 54.6% women), 1.01% (n = 983) had incident AF over a median follow-up of 361 days. The adjusted incidence rate was 8.39 (95% CI: 6.67-9.99) and 11.70 (95% CI: 10.9-12.55) per 1,000 person-years in the SGLT2i and DPP4i groups, respectively. SGLT2is were associated with a significantly lower risk of incident AF (HR 0.73; 95% CI, 0.57 to 0.91; p = 0.01) than DPP4is. The risk reduction of incident AF was significant in non-Hispanic White individuals and subgroups with existing atherosclerotic cardiovascular diseases and chronic kidney disease. Conclusion: Compared to the use of DPP4i, that of SGLT2i was associated with a lower risk of AF in patients with T2D. Our findings contribute to the real-world evidence regarding the effectiveness of SGLT2i in preventing AF and support a tailored therapeutic approach to optimize treatment selection based on individual characteristics.

Implementation of statistical features of a Bayesian two-armed responsive adaptive randomization trial with post hoc analysis of time trend drift.

Bayesian adaptive designs with response adaptive randomization (RAR) have the potential to benefit more participants in a clinical trial. While there are many papers that describe RAR designs and results, there is a scarcity of works reporting the details of RAR implementation from a statistical point exclusively. In this paper, we introduce the statistical methodology and implementation of the trial Changing the Default (CTD). CTD is a single-center prospective RAR comparative effectiveness trial to compare opt-in to opt-out tobacco treatment approaches for hospitalized patients. The design assumed an uninformative prior, conservative initial allocation ratio, and a higher threshold for stopping for success to protect results from statistical bias. A particular emerging concern of RAR designs is the possibility that time trends will occur during the implementation of a trial. If there is a time trend and the analytic plan does not prespecify an appropriate model, this could lead to a biased trial. Adjustment for time trend was not pre-specified in CTD, but post hoc time-adjusted analysis showed no presence of influential drift. This trial was an example of a successful two-armed confirmatory trial with a Bayesian adaptive design using response adaptive randomization.

Comparative cardiovascular and renal effectiveness of empagliflozin and dapagliflozin: scandinavian cohort study.

AIMS: To assess the comparative cardiovascular and renal effectiveness and safety of empagliflozin vs. dapagliflozin among patients with type 2 diabetes in routine clinical practice. METHODS: Cohort study using data from nationwide registers in Sweden, Denmark and Norway, from June 2014 to June 2021 including 141 065 new users of empagliflozin and 58 306 new users of dapagliflozin. Coprimary outcomes were major cardiovascular events (myocardial infarction, stroke, and cardiovascular death), heart failure (hospitalization or death because of heart failure) and serious renal events (renal replacement therapy, hospitalization for renal events, and death from renal causes). Secondary outcomes were the individual components of the primary outcomes, any cause death and diabetic ketoacidosis. RESULTS: Use of empagliflozin vs. dapagliflozin was associated with similar risk of major cardiovascular events (adjusted incidence rate: 15.9 vs. 15.8 events per 1000 person-years; HR 1.02, [95% CI 0.97-1.08]), heart failure (6.5 vs. 6.3 events per 1000 person-years; HR 1.05 [0.97-1.14]) and serious renal events (3.7 vs. 4.1 events per 1000 person-years; HR 0.97 [0.87-1.07]). In secondary outcome analyses, the HRs for use of empagliflozin vs. dapagliflozin were 1.00 (0.93-1.07) for myocardial infarction, 1.03 (0.95-1.12) for stroke, 1.01 (0.92-1.13) for cardiovascular death, 1.06 (1.00-1.11) for any cause death, 0.77 (0.60-0.99) for renal replacement therapy, 1.20 (0.75-1.93) for renal death, 1.01 (0.90-1.12) for hospitalization for renal events and 1.12 (0.94-1.33) for diabetic ketoacidosis. CONCLUSIONS: Use of empagliflozin and dapagliflozin was associated with similar risk of cardiovascular and renal outcomes, mortality and diabetic ketoacidosis.

Comparative Effectiveness of Patient-Driven versus Standardized Diabetes Shared Medical Appointments: A Pragmatic Cluster Randomized Trial.

BACKGROUND: Diabetes self-management education and support can be effectively and efficiently delivered in primary care in the form of shared medical appointments (SMAs). Comparative effectiveness of SMA delivery features such as topic choice, multi-disciplinary care teams, and peer mentor involvement is not known. OBJECTIVE: To compare effects of standardized and patient-driven models of diabetes SMAs on patient-level diabetes outcomes. DESIGN: Pragmatic cluster randomized trial. PARTICIPANTS: A total of 1060 adults with type 2 diabetes in 22 primary care practices. INTERVENTIONS: Practice personnel delivered the 6-session Targeted Training in Illness Management (TTIM) curriculum using either standardized (set content delivered by a health educator) or patient-driven SMAs (patient-selected topic order delivered by health educators, behavioral health providers [BHPs], and peer mentors). MAIN MEASURES: Outcomes included self-reported diabetes distress and diabetes self-care behaviors from baseline and follow-up surveys (assessed at 1st and final SMA session), and HbA1c, BMI, and blood pressure from electronic health records. Analyses used descriptive statistics, linear regression, and linear mixed models. KEY RESULTS: Both standardized and patient-driven SMAs effectively improved diabetes distress, self-care behaviors, BMI (- 0.29 on average), and HbA1c (- 0.45% (mmol/mol) on average, 8.3 to 7.8%). Controlling for covariates, there was a small, significant effect of condition on overall diabetes distress in favor of standardized SMAs (F(1,841) = 4.3, p = .04), attributable to significant effects of condition on emotion and regimen distress subscales. There was a small, significant effect of condition on diastolic blood pressure in favor of standardized SMAs (F(1,5199) = 4.50, p = .03). There were no other differences between conditions. CONCLUSIONS: Both SMA models using the TTIM curriculum yielded significant improvement in diabetes distress, self-care, and HbA1c. Patient-driven diabetes SMAs involving BHPs and peer mentors and topic selection did not lead to better clinical or patient-reported outcomes than standardized diabetes SMAs facilitated by a health educator following a set topic order. NIH TRIAL REGISTRY NUMBER: NCT03590041.

Remdesivir is Associated with Reduced Mortality in Patients Hospitalized for COVID-19 Not Requiring Supplemental Oxygen.

Background: Remdesivir has demonstrated benefit in some hospitalized patients with coronavirus disease 2019 (COVID-19) on supplemental oxygen and in nonhospitalized patients breathing room air. The durability of this benefit across time periods with different circulating severe acute respiratory syndrome coronavirus 2 variants of concern (VOC) is unknown. This comparative effectiveness study in patients hospitalized for COVID-19 and not receiving supplemental oxygen at admission compared those starting remdesivir treatment in the first 2 days of admission with those receiving no remdesivir during their hospitalization across different VOC periods. Method: Using a large, multicenter US hospital database, in-hospital mortality rates were compared among patients hospitalized for COVID-19 but not requiring supplemental oxygen at admission between December 2020 and April 2022. Patients receiving remdesivir at hospital admission were matched 1:1 to those not receiving remdesivir during hospitalization, using propensity score matching. Cox proportional hazards models were used to assess 14- and 28-day in-hospital mortality rates or discharge to hospice. Results: Among the 121 336 eligible patients, 58 188 remdesivir-treated patients were matched to 17 574 unique patients not receiving remdesivir. Overall, 5.4% of remdesivir-treated and 7.3% in the non-remdesivir group died within 14 days, and 8.0% and 9.8%, respectively, died within 28 days. Remdesivir treatment was associated with a statistically significant reduction in the in-hospital mortality rate compared with non-remdesivir treatment (14-day and 28-day adjusted hazard ratios [95% confidence interval], 0.75 [0.68-0.83] and 0.83 [0.76-0.90], respectively). This significant mortality benefit endured across the different VOC periods. Conclusions: Remdesivir initiation in patients hospitalized for COVID-19 and not requiring supplemental oxygen at admission was associated with a significantly reduced in-hospital mortality rate. These findings highlight a potential survival benefit when clinicians initiated remdesivir on admission across the dominant variant eras of the evolving pandemic.

Comparative effectiveness of antihypertensive monotherapies in primary prevention of cardiovascular events-a real-world longitudinal inception cohort study.

Introduction: Antihypertensive drugs are used preventatively to lower the risk of cardiovascular disease events. Comparative effectiveness studies on angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), beta-blockers (BBs), calcium channel blockers (CCBs), and thiazides have yielded inconsistent results and given little consideration to patient adherence. Using a longitudinal cohort and considering time-varying adherence and confounding factors, we aimed to estimate the real-world effectiveness of five major antihypertensive drug monotherapies in the primary prevention of cardiovascular events. Methods: Eligible patients for a retrospective inception cohort study were selected using information obtained from the University of Groningen IADB.nl pharmacy prescription database. Cohort 1 comprised adherent patients with a follow-up time exceeding 1 year, and cohort 2 comprised all patients independent of adherence. The exposures were ACEIs, ARBs, BBs, CCBs, and thiazides. The primary outcome was the time to the first prescription for an acute cardiac drug therapy (CDT) measured using valid drug proxies to identify the first major cardiovascular event. A per-protocol analytical approach was adopted with inverse probability of treatment weighted (IPTW), time-varying Cox regression analysis to obtain the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: In cohort 1 (n = 22,441), 1,294 patients (5.8%) were prescribed an acute CDT with an average follow-up time of 4.2 ± 2.8 years. Following IPTW, the hazard measures of ARBs and thiazides were lower than those of BBs (HRs: 0.79 and 0.80, respectively; 95% CIs: 0.64-0.97 and 0.69-0.94, respectively). Among drug-treated diabetic patients, the hazard measures were even lower, with HR point estimates of 0.43 (CI: 0.19-0.98) for ARBs and 0.32 (CI: 0.13-0.82) for thiazides. In cohort 2 (n = 33,427) and sensitivity analysis, the comparative effectiveness results for thiazides and BBs were similar to those for cohort 1. Conclusion: The findings of this real-world analysis suggest that the incidence of CDT associated with long-term thiazide or ARB monotherapy is lower than the incidence of CDT with BBs, notably among high-risk patients. Incidences of CDT associated with ACEIs and CCBs were comparable relative to those associated with BBs.

Partial Hepatectomy and Ablation for Survival of Early-Stage Hepatocellular Carcinoma Patients: A Bayesian Emulation Analysis.

Partial hepatectomy and ablation therapy are two widely used surgical procedures for localized early-stage hepatocellular carcinoma (HCC) patients. This article aimed to evaluate their relative effectiveness in terms of overall survival. An emulation analysis approach was first developed based on the Bayesian technique. We estimated propensity scores via Bayesian logistic regression and adopted a weighted Bayesian Weibull accelerated failure time (AFT) model incorporating prior information contained in the published literature. With the Surveillance, Epidemiology, and End Results (SEER)-Medicare data, an emulated target trial with rigorously defined inclusion/exclusion criteria and treatment regimens for early-stage HCC patients over 66 years old was developed. For the main cohort with tumor size less than or equal to 5 cm, a total of 1146 patients were enrolled in the emulated trial, with 301 and 845 in the partial hepatectomy and ablation arms, respectively. The analysis suggested ablation to be significantly associated with inferior overall survival (hazard ratio [HR] = 1.35; 95% credible interval [CrI]: 1.14, 1.60). For the subgroup with tumor size less than or equal to 3 cm, there was no significant difference in overall survival between the two arms (HR = 1.15; 95% CrI: 0.88, 1.52). Overall, the comparative treatment effect of ablation and partial hepatectomy on survival remains inconclusive. This finding may provide further insight into HCC clinical treatment.

Comparative effectiveness of lazertinib in patients with EGFR T790M-positive non-small-cell lung cancer using a real-world external control.

Lazertinib is a recently developed third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors used for patients with advanced EGFR T790M-positive non-small-cell lung cancer. We evaluated the effectiveness of lazertinib compared with osimertinib using an external control. We obtained individual patient data for the lazertinib arm from the LASER201 trial and the osimertinib arm from registry data at the Samsung Medical Center. In total, 75 and 110 patients were included in the lazertinib and osimertinib groups, respectively. After propensity score matching, each group had 60 patients and all baseline characteristics were balanced. The median follow-up duration was 22.0 and 29.6 months in the lazertinib and osimertinib group, respectively. The objective response rate (ORR) were 76.7% and 86.7% for lazertinib and osimertinib, respectively (p = 0.08). The median progression-free survival (PFS) was 12.3 months (95% confidence interval [CI] 9.5-19.1) and 14.4 months (95% CI 11.8-18.1) for the lazertinib and osimertinib group, respectively (hazard ratio [HR] 0.97; 95% CI 0.64-1.45, p = 0.86). The median overall survival with lazertinib was not reached and that with osimertinib was 29.8 months (HR 0.44; 95% CI 0.25-0.77, p = 0.005). Our study suggests that lazertinib has an ORR and PFS comparable to those of osimertinib and has the potential for superior survival benefits.

Real-world comparative effectiveness and safety of pembrolizumab for PD-L1≥50% metastatic non-small-cell lung cancer.

Background: Despite the demonstrated efficacy of pembrolizumab in KEYNOTE-024, effectiveness and safety in routine practice remain unclear. Methods: The authors identified first-line pembrolizumab or chemotherapy patients from April 2013 to March 2021. The primary outcome was overall survival; the secondary safety outcomes included rates of hospitalization, emergency department visits, specialist visits, and adverse events. Baseline differences were adjusted using propensity score matching (1:1). Results: The matched cohort included 2284 pairs. Median overall survival for pembrolizumab (13.0 months) was significantly longer than for chemotherapy (9.2 months), with a hazard ratio of 0.81 (95% CI: 0.71-0.92). Pembrolizumab patients reported significantly more adverse events and specialist visits, as well as a higher 1-year cumulative incidence of direct hospitalizations. Conclusion: The survival benefit of first-line pembrolizumab persists in the real world, although with increased toxicity and diminished benefit.

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Evaluating the Effectiveness of Systemic Heparin During Arteriovenous Fistula Creation by Emulating a Target Trial.

Most of the 800,000 people living with end-stage kidney disease in the United States rely on a functioning vascular access to provide life-sustaining hemodialysis, yet one-third of arteriovenous fistulas experience early failures. Determining the safety and effectiveness of systemic heparin during fistula creation could improve the quality and quantity of life for these vulnerable patients. In this paper, a pragmatic randomized trial was emulated to assess the effect of systemic heparin administration (vs. none) during radiocephalic arteriovenous fistula creation on early bleeding and thrombosis using data from two international multicenter randomized trials performed between 2014 and 2019. Marginal risks were estimated using inverse probability weighted parametric survival analysis and confidence intervals were generated with bootstrapping. A total of 914 patients were enrolled and 61% received systemic heparin; median (IQR) age was 58 (49, 67) years and 45% were on hemodialysis at enrollment. No difference in the risk of bleeding events was observed, with a risk difference (95% CI) at 14 days of -0.1% (-1.6, 1.4). The risk of access thrombosis was lower in the heparin group, with a risk of 3.7% (2.6, 4.8) after heparin and 5.3% (3.4, 7.4) without heparin at 14 days (risk ratio 0.72, 95% CI 0.50, 0.98).

Toward a core outcome set for faecal incontinence-A systematic review of outcomes reported in the literature.

AIM: Faecal incontinence (FI) is a prevalent issue which can have a detrimental impact on the patient's quality of life. Current international guidelines lack strong treatment recommendations due to few studies in the field, in combination with the heterogeneity in outcome reporting. To address this, a core outcome set (COS) is proposed to standardize outcome reporting in FI studies, facilitating meta-analyses and enhancing therapeutic recommendations. Through several steps outlined by COMET 'what' to measure will be determined prior to determining 'how' to measure these outcomes. This systematic review aims to identify 'what' outcomes have been used in FI intervention studies so far in adult patients as a starting phase for the development of a future COS for FI. METHOD: Medline, Embase and the Cochrane library were searched to identify all outcomes reported in comparative effectiveness trials assessing one or more treatment option in adult patients suffering from FI. The outcomes were categorized according to the Core Outcome Measurement in Effectiveness Trials (COMET) taxonomy to standardize outcome terminology, assess completeness, and inform subsequent steps in COS development. RESULTS: A total of 109 studies were included, which revealed 51 unique outcomes classified into 38 domains within four core areas. On average four outcomes were reported per study (range 1-11). The most commonly reported outcomes were "severity of FI" (83%), "quality of life" (64%), "number of FI episodes" (40%), "anorectal motor function" (39%), and "frequency of bowel movements" (16%). CONCLUSION: This systematic review offers an overview of outcomes reported in FI studies, highlighting the heterogeneity between studies. This heterogeneity emphasizes the need for standardizing outcome reporting which can be established through the creation of a COS.

A Comprehensive Analysis of Conventional Acupuncture and Pharmacological Approaches for Cardiac Arrhythmias: An Umbrella Review.

With a global incidence of approximately 3.4% and an annual mortality rate of 3.7 million, cardiac arrhythmias (CAs) are a pressing global health issue. Their increasing prevalence, especially among older people, is intensifying the challenge for health care systems worldwide. This study aims to compare the safety and effectiveness of acupuncture and pharmacological treatments for CAs, addressing critical gaps in understanding optimal therapeutic approaches. A search of PubMed, EMBASE, and the Cochrane database of systematic reviews was performed to identify data compiled through September 2023 for this umbrella review. Randomized controlled trials (RCTs) as the foundation for meta-analyses and peer-reviewed systematic reviews were the primary focus of the literature search. The Grading of Recommendations Assessment, Development, and Evaluation method was used to assess the overall certainty of the evidence, whereas AMSTAR 2 and the Cochrane Collaboration tool were used to evaluate the quality of the included reviews. Following a comprehensive review, three systematic analyses of 27 RCTs were integrated. Acupuncture led to a slightly greater reduction in the recurrence rate of paroxysmal supraventricular tachycardia (SVT) compared to standard pharmaceutical therapy (risk ratio [RR], 1.06; 95% confidence interval [CI], 0.88-1.27; I2 = 56%; P = .55), although the difference was not statistically significant. In contrast, acupuncture significantly outperformed pharmacological treatment in the context of ventricular premature beats (VPBs) (RR, 1.16; 95 CI, 1.08-1.25; I2 = 0%; P < .0001). The reduction in paroxysmal atrial fibrillation (AF)/atrial flutter was increased with acupuncture, albeit without statistical significance (RR, 1.12; 95% CI, 0.88-1.42; I2 = 0%; P = .36). Acupuncture also led to a greater reduction in heart rate (HR) compared to pharmaceutical treatment despite notable heterogeneity and a lack of statistical significance (mean difference, -1.55; 95% CI, -41.37 to 38.28; I2 = 99%; P = .94). Adverse events were effectively managed, affirming the favorable safety profile of acupuncture. Our study suggests that acupuncture leads to a greater reduction in the recurrence rates of VPBs, AF, and atrial flutter but not significantly so in paroxysmal SVT or post-treatment HR. While promising for specific arrhythmias, the varying effectiveness of acupuncture underscores the need for further research and clinical assessment to determine its precise role and suitability in managing particular cardiac conditions.

Overview of the 2023 FDA Circulatory System Devices Advisory Panel meeting on the Recor Paradise Ultrasound-Based Renal Denervation System.

Hypertension continues to be a prominent, avoidable factor contributing to major vascular issues on a global scale. Even with lifestyle adjustments and more aggressive medical treatments, maintaining optimal blood pressure levels remains challenging. This challenge has driven the emergence of device-oriented approaches to address hypertension. To assess the safety and efficacy of the Recor Paradise Ultrasound Renal Denervation System, the Circulatory System Devices Panel was convened by the US Food and Drug Administration (FDA). This manuscript provides a condensed overview of the information put forth by the sponsor and the FDA, along with an account of the considerations and conversations that took place during the meeting.

Emulation of randomized trials of direct oral anticoagulants with claims data and implications for new Factor XI inhibitors.

Direct oral anticoagulants (DOACs) revolutionized the management of thromboembolic disorders. Clinical care may be further improved as Factor XIs undergo large-scale outcome trials. What role can non-randomized database studies play in expediting understanding of these drugs in clinical practice? The RCT-DUPLICATIVE Initiative emulated the design of eight DOAC randomized clinical trials (RCT) using non-randomized claims database studies. RCT study design parameters and measurements were closely emulated by the database studies and produced highly concordant results. The results of the single database study that did not meet all agreement metrics with the specific RCT it was emulating were aligned with a meta-analysis of six trials studying similar questions, suggesting the trial result was an outlier. Well-designed database studies using fit-for-purpose data came to the same conclusions as DOAC trials, illustrating how database studies could complement RCTs for Factor XI inhibitors-by accelerating insights in underrepresented populations, demonstrating effectiveness and safety in clinical practice, and testing broader indications.

Advancements in de Quervain Tenosynovitis Management: A Comprehensive Network Meta-Analysis.

PURPOSE: This study presents a network meta-analysis aimed at evaluating nonsurgical treatment modalities for de Quervain tenosynovitis. The primary objective was to assess the comparative effectiveness of nonsurgical treatment options. METHODS: The systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Searches were performed in multiple databases, and studies meeting predefined criteria were included. Data extraction, risk of bias assessment, and statistical analysis were carried out to compare treatment modalities. The analysis was categorized into short-term (within six weeks), medium-term (six weeks up to six months), and long-term (one year) follow-up. RESULTS: The analysis included 14 randomized controlled trials encompassing various treatment modalities for de Quervain tenosynovitis. In the short-term, extracorporeal shockwave therapy demonstrated statistically significant improvement in visual analog scale pain scores compared with placebo. Extracorporeal shockwave therapy also ranked highest in the treatment options based on its treatment effects. Corticosteroid injections (CSIs) combined with casting and laser therapy with orthosis showed favorable outcomes. Corticosteroid injection alone, platelet-rich plasma injections alone, acupuncture, and orthosis alone did not significantly differ from placebo in visual analog scale pain score. In the medium-term, extracorporeal shockwave therapy remained the top-ranking option for visual analog scale pain score, followed by CSI with casting. In the long-term (one year), CSI alone and platelet-rich plasma injections demonstrated sustained pain relief. Combining CSI with orthosis also appeared promising when compared with CSI alone. CONCLUSIONS: Corticosteroid injection with a short duration of immobilization remains the primary and effective treatment for de Quervain tenosynovitis. Extracorporeal shockwave therapy can be considered a secondary option. Alternative treatment modalities, such as isolated therapeutic injection, should be approached with caution because they did not show substantial benefits over placebo. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.

Comparison of mortality and amputation after lower extremity bypass versus peripheral vascular intervention in patients with chronic limb-threatening ischemia and comorbid chronic kidney disease.

OBJECTIVE: Comorbid chronic kidney disease (CKD) is associated with worse outcomes for patients with chronic limb-threatening ischemia (CLTI). However, comparative effectiveness data are limited for lower extremity bypass (LEB) vs peripheral vascular intervention (PVI) in patients with CLTI and CKD. We aimed to evaluate (1) 30-day all-cause mortality and amputation and (2) 5-year all-cause mortality and amputation for LEB vs PVI in patients with comorbid CKD. METHODS: Individuals who underwent LEB and PVI were queried from the Vascular Quality Initiative with Medicare claims-linked outcomes data. Propensity scores were calculated using 13 variables, and a 1:1 matching method was used. The mortality risk at 30 days and 5 years in LEB vs PVI by CKD was assessed using Kaplan-Meier and Cox proportional hazards models, with interaction terms added for CKD. For amputation, cumulative incidence functions and Fine-Gray models were used to account for the competing risk of death, with interaction terms for CKD added. RESULTS: Of 4084 patients (2042 per group), the mean age was 71.0 ± 10.8 years, and 69.0% were male. Irrespective of CKD status, 30-day mortality (hazard ratio [HR]: 0.94, 95% confidence interval [CI]: 0.63-1.42, P = .78) was similar for LEB vs PVI, but LEB was associated with a lower risk of 30-day amputation (sub-HR [sHR]: 0.66, 95% CI: 0.44-0.97, P = .04). CKD status, however, did not modify these results. Similarly, LEB vs PVI was associated with a lower risk of 5-year mortality (HR: 0.79, 95% CI: 0.71-0.88, P < .001) but no difference in 5-year amputation (sHR: 1.03, 95% CI: 0.89-1.20, P = .67). CKD status did not modify these results. CONCLUSIONS: Regardless of CKD status, patients had a lower risk of 5-year all-cause mortality and 30-day amputation with LEB vs PVI. Results may help inform preference-sensitive treatment decisions on LEB vs PVI for patients with CLTI and CKD, who may commonly be deemed too high risk for surgery.