Issue: Newsletter 6 | October 1, 2025
| Citation of Articles | PICO | Main Results | Risk of Bias |
|---|---|---|---|
| Wolfhagen N, Boldingh JJ, Bom WJ, Posthuma LM, Scheijmans JCG, van der Leeuw BMF, et al. A care bundle added to standard care versus standard care for the prevention of surgical site infections after abdominal surgery (EPO2CH trial): a randomised, open label, pragmatic, superiority multicentre trial. Lancet Reg Health Eur. 2025;58:101448. doi:10.1016/j.lanepe.2025.101448 | P: 1777 patients undergoing elective abdominal surgery with incisions >5 cm, randomized across 7 hospitals in the Netherlands (mean age ~63, 56% female) I: EPO2CH perioperative care bundle (high FiO₂, goal-directed fluid therapy, normothermia, perioperative glucose control, wound irrigation) C: Standard care (including preoperative systemic antibiotic prophylaxis and alcohol-based skin preparation) O: Incidence of surgical site infection (SSI) within 30 days (primary); serious adverse events (secondary) |
SSI incidence was similar between groups: 18.4% (160/869) in EPO2CH vs 18.9% (172/908) in control; RR 0.98 (95% CI 0.81–1.18). Per-protocol analysis also showed no significant benefit (RR 0.91, 95% CI 0.60–1.37). Serious adverse events occurred in 33.3% vs 33.5% (RR 0.99, 95% CI 0.87–1.23). The care bundle did not reduce SSI despite adherence to multiple guideline-recommended interventions. | Moderate risk: Open-label design increases potential for performance and detection bias. Randomisation per hospital/day and multicentre setting improve generalisability. High follow-up completeness reduces attrition bias. However, pragmatic design and bundled intervention may dilute specific effects of individual components. |
| Thompson GR, Huang H, Feng S, Yu Y, Soriano A, Cornely OA, et al. Rezafungin versus caspofungin for the treatment of candidemia and invasive candidiasis: results from the double-blind, randomized phase 3 ReSTORE trial including the China extension study. Open Forum Infect Dis. 2025 Sep 15; ofaf555. doi:10.1093/ofid/ofaf555 | P: 246 adults with candidemia and/or invasive candidiasis (122 rezafungin, 124 caspofungin) I: Weekly rezafungin (400/200 mg) for ≤28 days C: Daily caspofungin (70/50 mg) for ≤28 days O: Primary endpoints: Day 30 all-cause mortality, Day 14 global cure; secondary endpoints: mycological eradication, time to negative blood culture, safety |
Rezafungin was non-inferior to caspofungin for both primary endpoints. Day 30 all-cause mortality was 25.2% vs 24.8% (difference 0.4%; 95% CI −10.8, 11.6). Day 14 global cure was 56.5% vs 57.3% (difference −1.0%; 95% CI −13.5, 11.6). Day 5 mycological eradication was higher with rezafungin (68.7% vs 63.2%) and median time to negative blood culture was shorter (26.5 vs 38.8 hours). Serious adverse events occurred at similar rates (53.3% vs 53.7%). | Low to moderate risk: Double-dummy blinding not described, raising potential for performance bias. Randomisation and predefined non-inferiority margins strengthen internal validity. Relatively small sample size limits power for subgroup analyses, but consistency of primary outcomes across global and China cohorts supports reliability. |
| Ruiz-Tagle C, Seguel R, Villarroel L, Bernales M, Vargas-García S, Pizarro A, et al. Reducing household tuberculosis transmission: a pilot cluster-randomized controlled trial. Clin Infect Dis. 2025 Sep 26; doi:10.1093/cid/ciaf526 • Editorial Commentary: Burzynski JN, Schluger NW. (Un)masking TB. Clin Infect Dis. 2025 Sep 27; doi:10.1093/cid/ciaf528 |
P: 157 patients with newly diagnosed pulmonary tuberculosis and 384 household contacts (56.3% women, mean age 34.6 years; 32.3% baseline QFT positivity) in Santiago, Chile I: Two-week bundled intervention including education, mask use, household ventilation, and nightly separation of TB patients C: Standard of care O: QuantiFERON®-TB Gold Plus (QFT) conversion in household contacts at 12-week follow-up |
Among 216 contacts with negative baseline QFT, 179 (82.9%) completed follow-up. QFT conversions occurred in 11/86 (12.8%) HHCs in the intervention group and 10/93 (10.8%) in the control group (incidence risk ratio 1.10, 95% CI 0.71–1.71, p=0.849). Adherence to the respiratory bundle was moderate (53% on day 7, 54% on day 14). Overall, the intervention did not reduce TB infections in household contacts. | Moderate risk: The open-label cluster design could introduce performance and detection bias. Moderate follow-up completion (82.9%) may slightly influence attrition bias. Small sample size and pilot nature limit statistical power and generalizability. Adherence challenges may have reduced intervention effectiveness. |
| Taweesuk A, Rattanaumpawan P, Rachakhom S, Wangchinda W, Assanasen S, Thamlikitkul V. Cluster-randomized controlled trial of enhanced carbapenem-resistant Enterobacterales prevention program in general medicine wards, Siriraj Hospital. Clin Infect Dis. 2025 Sep 22; doi:10.1093/cid/ciaf523 | P: 363 adults with ≥1 CRE risk factor admitted to six general medical wards at Siriraj Hospital (174 intervention, 189 control; 1,684 vs 1,517 patient-days) I: Enhanced CRE prevention program (standard IPC plus monthly staff education, real-time CRE acquisition notifications, and contact-precaution reminders) C: Standard infection prevention and control (sIC) O: CRE acquisition incidence and CRE acquisition-free time |
Cumulative CRE acquisition was slightly lower in the intervention group (36.8% vs 46.6%, p=0.06), with a significantly lower incidence rate per patient-day (0.038 vs 0.058, p=0.007). Post-hoc analysis excluding acquisitions within 24 hours showed no significant difference (25.7% vs 33.6%, p=0.16). Unadjusted HR for remaining CRE-free was 0.72 (95% CI 0.52–1.00, p=0.05); adjusted HR 0.75 (95% CI 0.54–1.05, p=0.09). No differences in all-cause mortality or hospital length of stay. Overall, the enhanced program tended to reduce CRE acquisition and prolong CRE-free survival. | Moderate risk: Cluster-randomized design reduces individual randomization bias but may introduce ward-level confounding. Open-label design could affect staff behavior (performance bias). Post-hoc analyses and relatively small sample size limit statistical power. Surveillance and adherence to interventions were monitored but could vary across wards. |
| Mølgaard J, Grønbæk KK, Rasmussen SS, Eiberg JP, Jørgensen LN, Achiam MP, et al. Continuous vital sign monitoring at the surgical ward for improved outcomes after major noncardiac surgery: a randomized clinical trial. Anesth Analg. 2025;141(4):807-817. doi:10.1213/ANE.0000000000007606 | P: 400 adult patients undergoing major noncardiac surgery (200 intervention, 200 control) on a general postoperative ward I: Standard of care plus continuous wireless vital sign monitoring with real-time alerts to staff smartphones C: Standard of care (manual intermittent vital sign monitoring) O: Cumulative duration of severe vital sign deviations; adverse events within 30 days |
Median duration of severe vital sign deviations was 60 [25–136] min/day in the intervention group versus 76 [28–192] min/day in the control group (P = 0.19). Duration of SpO₂ <88% decreased by a mean of 47 min/day (95% CI 18–80, P = 0.02). Adverse events occurred in 42.5% vs 31.5% (P = 0.02), while serious adverse events were 34.5% vs 29.5% (P = 0.39). Continuous monitoring reduced desaturations but did not significantly reduce overall cumulative severe vital sign deviations. | Low-moderate risk: Patients and outcome assessors were blinded, reducing detection bias. Intervention was unblinded to staff, introducing potential performance bias. Single-center setting may limit generalizability. Missing data not reported but seems minimal given full follow-up of 400 patients. |
| Kalia S, Nath P, Anand AC, Gupta S, Verma A, Mallick B, et al. Effect of oral rifaximin for prevention of infected pancreatic necrosis and mortality in severe acute pancreatitis: an open-label randomized controlled trial. Pancreatology. 2025 Sep 16; doi:10.1016/j.pan.2025.09.009 | P: 100 hospitalized patients with predicted severe acute pancreatitis I: Standard treatment plus rifaximin 550 mg orally twice daily for 14 days C: Standard treatment alone O: Development of infected pancreatic necrosis and in-hospital mortality |
No significant difference in incidence of infected pancreatic necrosis (31 vs 35, p=0.507) or in-hospital mortality (9 vs 14, p=0.603). Median ICU stay (3 vs 5 days, p=0.209) and organ failure (56% vs 60%, p=0.525) were similar. Length of hospitalization was significantly shorter in the rifaximin group (median 8 vs 11.5 days, p=0.002). Overall, rifaximin did not reduce infection or mortality but shortened hospital stay. | Moderate risk: Open-label design may introduce performance and detection bias. Single-center study with small sample size limits statistical power and generalizability. Primary endpoints were objective, reducing detection bias somewhat, but secondary outcomes like length of stay could be influenced by clinical management decisions. |
| Wang Q, Ke J, Chen Y, Xu H, Wu D, Ke L, et al. Early energy delivery and 28-day mortality in critically ill patients with sepsis: post hoc analysis of a multicenter cluster-randomised controlled trial. J Crit Care. 2026;91:155265. doi:10.1016/j.jcrc.2025.155265 | P: 1,162 ICU patients with sepsis and expected ≥7-day ICU stay (median age 66, 66.3% male) stratified by nutritional risk (mNUTRIC score <5 vs ≥5) I: Early energy delivery ≥60% of target (25 kcal/kg ideal body weight) in first 7 days C: Lower energy delivery than target in first 7 days O: 28-day all-cause mortality |
In high nutritional risk patients (mNUTRIC ≥5), achieving ≥60% of energy target was associated with lower 28-day mortality (HR 0.588, 95% CI 0.388–0.891). No survival benefit was observed in low-risk patients (mNUTRIC <5). Restricted cubic spline analysis suggested a downward trend in mortality with increasing energy delivery in high-risk patients (P-nonlinear = 0.063). Results support individualized energy targets based on nutritional risk. | Moderate risk: Post hoc analysis of a multicentre trial may introduce selection and confounding biases. Nutritional interventions were not randomized for this specific analysis, limiting causal inference. Large sample size strengthens precision, but unmeasured confounders (e.g., illness severity, comorbidities) could influence outcomes. |
Minter DJ, Chow FC. Brief review: Neurosyphilis. Ann Neurol. 2025 Sep 2; doi:10.1002/ana.78016
Weiner AB. Unseen scars. JAMA. 2025 Sep 18; doi:10.1001/jama.2025.15402
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