Total Events Research Articles

Pipeline Vantage Embolization Device for the treatment of intracranial aneurysms: A systematic review and meta-analysis.

The Pipeline Vantage Embolization Device (PVED) is a novel coated flow diverter with reduced wire diameters to improve neoendothelialization and stent porosity. This systematic review evaluates the safety and efficacy of the PVED based on the current literature. Following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, a thorough literature search was conducted using PubMed, EMBASE, and Cochrane. The random effects model was used to calculate estimates with major neurological complications within 30 days of treatment as the primary safety endpoint and ≤1-year complete occlusion rate as the primary efficacy endpoint. Six single-arm studies (5 retrospective, 1 prospective) with 392 patients and 439 aneurysms (6.8% ruptured) were included. Antiplatelet regimens varied, but dual antiplatelet therapy was administered in the majority. The pooled technical success rate was 99.0% (95%CI, 98.0%-100%) with an average of 1.2 devices implanted per procedure. Balloon angioplasty was performed in 17.0% (95%CI, 6.4-27.6%) and adjunctive coiling in 28.0% (95%CI, 17.8-38.2%), with significant heterogeneity for both variables. Pooled estimates for major neurological complications were 3.5% (95%CI, 1.7%-5.2%) with total ischemic events in 4.1% (95% CI, 1.6%-6.6%) and hemorrhagic events in 1.0% (95% CI, 0.0%-1.9%). The rate of complete angiographic occlusion was 75.7% (95%CI, 70.7%-80.6%) at a mean follow-up of 7 months, with in-stent stenoses in 8.1% (95%CI, 4.5%-11.8%). The safety and efficacy profile of the PVED appears comparable to competing devices, with potentially fewer complications than first-generation flow diverters. Long-term and comparative studies are needed to further confirm these results.

Hypersensitivity Reactions Induced by Iodinated Contrast Media in Radiological Diagnosis: A Disproportionality Analysis Based on the FAERS Database.

This study aimed to evaluate the Pharmacovigilance (PV) and severity of hypersensitivity reactions induced by non-ionic Iodinated Contrast Media (ICM) in the radiology diagnosis reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS). We retrospectively reviewed the reports of ICM-induced hypersensitivity reactions submitted to the FAERS database between January 2015 and January 2023 and conducted a disproportionality analysis. The seven most common non-ionic ICM, including iohexol, iopamidol, ioversol, iopromide, iomeprol, iobitridol, and iodixanol, were chiefly analyzed. Our primary endpoint was the PV of non-ionic ICM-induced total hypersensitivity events. STATA 17.0 MP was used for statistical analysis. In total, 35357 reports of adverse reaction events in radiology diagnosis were retrieved from the FAERS database. Among them, 6181 reports were on hypersensitivity reaction events (mean age: 57.1 ± 17.8 years). The hypersensitivity reaction-related PV signal was detected for iohexol, ioversol, iopromide, iomeprol, iobitridol, and iodixanol, but not for iopamidol. The proportion of iomeprol-induced hypersensitivity reactions and the probability of ioversol-induced severe hypersensitivity reactions have been found to be significantly increased. The probability and severity of hypersensitivity reaction events in non-ionic ICM are different. Iohexol, ioversol, iopromide, iomeprol, iobitridol, and iodixanol have higher risks compared to iopamidol. In addition, the constituent ratio of hypersensitivity reactions induced by iomeprol is significantly increased, and the associated probability induced by ioversol is significantly increased.

Efficacy and Safety of Sanjie Analgesic Capsule in Patients with Endometriosis-Associated Pain: A Multicenter, 3:1 Randomized, Double-Blind, Placebo-Controlled Trial.

To assess the efficacy and safety of Sanjie Analgesic Capsule (SAC) in Chinese patients with endometriosis-associated pain. This was a multicenter, randomized, double-blind, placebo-controlled trial conducted at 15 centers between November 2013 and July 2017 in China. Eligible 323 patients with endometriosis were randomized at a 3:1 ratio to the SAC group (241 cases) and placebo group (82 cases) by stratified block randomization. Patients in the SAC or placebo groups were given SAC or placebo 1.6 g 3 times per day, orally, respectively since the first day of menstruation for 3 consecutive menstrual cycles. The primary endpoint was clinical response to dysmenorrhea evaluated using a 10-point Visual Analogue Scale at 3 and 6 months. The secondary endpoint was the pain score evaluated by VAS (chronic pelvic pain, defecation pain, and dyspareunia) at 3 and 6 months, and the pain recurrence rate at 6 months. Adverse events (AEs) were recorded during the study. A total of 241 women were included in the SAC group, and 82 were in the placebo group. Among these women, 217 (90.0%) and 71 (86.6%) completed the intervention, respectively. At 3 months, overall response rate (ORR) was significantly higher in women administered SAC (80.1%) compared with those who received a placebo (30.5%, P<0.01). Six months after treatment, the ORR for dysmenorrhea was 62.7% in the SAC group and 31.7% in the placebo group (P<0.01). Chronic pelvic pain and defecation pain were significantly improved by SAC compared with placebo (both P<0.05). The incidence rates of total AEs events in the SAC and placebo groups were 6.6% and 9.8%, respectively, and no significant difference was shown between the two groups (P=0.339). SAC is well-tolerated and may improve dysmenorrhea in women with endometriosis-associated pain. (Trial registration: ClinicalTrials.gov, No. NCT02031523).

Dose-response of daridorexant in insomnia disorder: An analysis of Phase 2 and 3 studies

ObjectiveDaridorexant is approved for the treatment of insomnia at two dose levels (25 and 50 mg). Dose-efficacy and -safety response relationships were evaluated using Phase 2 and 3 data. MethodsData (N = 2153) from one Phase 2 (daridorexant 5, 10, 25, 50 mg, placebo once daily for 1 month) and two Phase 3 studies (daridorexant 10 and 25 or 25 and 50 mg, placebo once daily for 3 months) were pooled. Dose-response analyses at 1 month of double-blind treatment were performed using a linear regression and a two-stage meta-analysis approach. Efficacy endpoints were polysomnography-derived wake after sleep onset, latency to persistent sleep (LPS), self-reported total sleep time and the Insomnia Daytime Symptoms and Impacts Questionnaire total score (only Phase 3 data for the latter). Safety endpoints were the incidence of total adverse events (AEs) and AEs corresponding to somnolence/fatigue. ResultsDose-responses for all efficacy endpoints were significant in the observed dose range (both statistical approaches, p < 0.01). All dose-response relationships were linear except for LPS (two-stage meta-analysis) which showed a change in slope above 10 mg without reaching a plateau. No significant dose-response was observed for any AE (both approaches, p > 0.05). The incidence of AEs corresponding to somnolence/fatigue was low at all doses and, without linear assumption (two-stage meta-analysis) there was no dose-dependency (p = 0.369). ConclusionsThe data support the use of 50 mg as the preferred daridorexant dose in patients with insomnia disorder to provide the greatest opportunity for efficacy with no increased risk for AEs, including somnolence/fatigue, compared to lower doses.

Patient Harm Events and Associated Cost Outcomes Reported to a Patient Safety Organization.

The aims of the study were to describe inpatient harm events detected via an automatic electronic trigger system (ETS) and to consider their financial consequences. Over a 27-month period, inpatient harm events were identified and documented in 1 healthcare system with 37 acute care facilities. Patients who experienced harm (all harm or preventable harm only) were compared with similar patients who did not. Clinical, financial, and demographic data were used to identify labor-adjusted direct variable costs (DVC) and potential differences in length of stay (LOS) associated with all-harm, preventable-harm, and nonharmed cohorts. Age-adjusted Charlson Comorbidity Index, case mix index, diagnosis-related groups, major diagnostic category, sex, age, location, diagnosis, adverse event category and subcategory, preventability, and harm severity were used to compare cohorts. Total harm events reported via the ETS and the health system's voluntary event reporting system were compared. Nearly 93,000 encounters for all-harm (n = 25,665) and nonharmed cohorts (n = 67,217) were compared by random sampling of diagnosis-related group-matched all-harm and nonharmed groups to ensure similar clinical conditions, as measured by Charlson Comorbidity Index and case mix index. Sampling (2 groups, n = 100 and n = 200) showed that increased LOS was associated with harm; yet other clinical comparators were similar across groups. the preventable-harm subcohort had longer LOS (10.7 versus 5.9 days) and higher DVC ($13,442 versus $8024) than the nonharmed cohort. Identification of harm events was nearly 6-fold higher with the ETS than with the voluntary event reporting system. Patients with preventable harm had increased LOS that was associated with higher DVC per preventable-harm encounter in a large US healthcare system.

Effects of extreme climate events and child mortality on total fertility rate in Bangladesh

Floods, storms, and temperature extremes are examples of extreme weather events that have a substantial influence on a country's demographic dynamics, including migration, fertility, and mortality. Changes in population size, composition, and distribution may result from these occurrences. This study, which spans the years 1966–2018, looks at how Bangladesh's total fertility rate (TFR) is affected by extreme weather events and child mortality, including neonatal, infant, male infant, and under-five mortality. We use data from secondary publicly accessible sources, such as the World Bank and The Emergency Events Database (EM-DAT), and we investigate the correlations using the autoregressive integrated moving average model (ARIMA), complemented by bivariate and multivariable analyses.Our findings from the univariate analysis are noteworthy. Total extreme climate events (β = −0.345, 95 % CI: 0.510, −0.180), as well as individual extreme climate events, such as extreme temperatures (β = −1.176, 95 % CI: 1.88, −0.47), floods (β = −0.644, 95 % CI: 1.0729, −0.216), and storms (β = −0.351, 95 % CI: 0.63159, −0.07154), exhibited negative associations with the TFR. Additionally, factors such as contraceptive prevalence rate (CPR) (β = −0.085, 95 % CI: 0.09072, −0.07954) and gross national income (GNI) per capita (β = −0.003, 95 % CI: 0.0041123, −0.0024234) were negatively correlated with the TFR. Conversely, various categories of child mortality, namely, infants (β = 0.041, 95 % CI: 0.040474, 0.042748), males (β = 0.038, 95 % CI:0.037719, 0.039891), and under-five (β = 0.026, 95 % CI:0.025684, 0.026979) – are positively associated with TFR. Controlling for two pivotal confounding factors, time and GNI per capita, yielded consistent results in the multivariate analysis. These findings provide insight on the dual impact of extreme weather events, which can reduce TFR while also raising it through infant mortality. This phenomena may be due to the increased vulnerability of younger children in climate-event-prone areas, prompting parents to seek additional children as both a replacement for lost offspring and an insurance mechanism against future child loss.

An overview of the CANVAS Program and CREDENCE trial: The primary outcomes and key clinical implications for those managing patients with type 2 diabetes.

To provide an overview of the primary outcomes and key clinical implications of the CANVAS Program and CREDENCE trial, which were event-driven, double-blind randomized controlled trials that established the efficacy and safety of canagliflozin in those with type 2 diabetes (T2D) and high cardiovascular risk (CV) or albuminuric chronic kidney disease (CKD). The CANVAS programme (CANVAS and CANVAS-R trials) randomized 10 142 people with T2D and high CV risk to canagliflozin or placebo and followed them for a median of 126 weeks. The primary efficacy outcome was met, with canagliflozin treatment associated with a 14% reduction in major adverse CV events (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.75 to 0.97; p < 0.001) as compared to placebo. The CREDENCE trial randomized 4401 individuals with T2D and albuminuric CKD to canagliflozin or placebo and followed them for 109 weeks. The CREDENCE trial also met its primary endpoint; canagliflozin treatment was associated with a 30% reduction in the composite of kidney failure, sustained doubling of serum creatinine level, or death from kidney or CV causes (HR 0.70, 95% CI 0.59 to 0.82; p < 0.001). Substantial reductions in hospitalization for heart failure (CANVAS: HR 0.67, 95% CI 0.52 to 0.87; CREDENCE: HR 0.61, 95% CI 0.47 to 0.80) and other key CV and kidney outcomes were also identified. Relative clinical benefits were consistent across subgroups defined by baseline age, sex, kidney function and history of CV disease but absolute benefits were greatest in those at highest baseline risk. Total serious adverse events were less common with canagliflozin treatment. Concerns about amputation and fracture risk observed in the CANVAS Program were not seen in CREDENCE and appear to have been spurious chance findings. Canagliflozin reduced important CV, kidney and mortality outcomes in those with T2D and high CV risk or CKD across diverse patient groups, with a good safety profile. Taken together with the other sodium-glucose cotransporter-2 inhibitor CV and renal outcomes trials, these landmark findings have changed the treatment landscape for patients worldwide.

Role of spot urinary sodium in outpatients with heart failure

Introduction and objectivesSpot determination of urinary sodium (UNa+) has emerged as a useful tool for monitoring diuretic response in patients with acute heart failure (AHF). However, the evidence in outpatients is scarce. We aimed to examine the relationship between spot UNa+ levels and the risk of mortality and worsening heart failure (WHF) events in individuals with chronic HF. MethodsThis observational and ambispective study included 1145 outpatients with chronic HF followed in a single center specialized HF clinic. UNa+ assessment was carried out 1-5 days before each visit. The endpoints of the study were the association between UNa+ and risk of a) long-term death and b) AHF-hospitalization and total WHF events (including AHF-hospitalization, emergency department visits or parenteral loop-diuretic administration in HF clinic), assessed by multivariate Cox and negative binomial regressions. ResultsThe mean±standard deviation of age was 73±11 years, 670 (58.5%) were men, 902 (78.8%) were on stable NYHA class II, and 595 (52%) had LFEF ≥50%. The median (interquartile range) UNa+ was 72 (51-94) mmol/L. Over a median follow-up of 2.63 (1.70-3.36) years, there were 293 (25.6%) deaths and 382 WHF events (244 AHF-admissions) in 233 (20.3%) patients. After multivariate adjustment, baseline UNa+ was inverse and linearly associated with the risk of total WHF (IRR, 1.07; 95%CI, 1.02-1.12; P=.007) and AHF-admissions (IRR, 1.08; 95%CI, 1.02-1.14; P=.012) and borderline associated with all-cause mortality (HR, 1.04; 95%CI, 0.99-1.09; P=.068). ConclusionsIn outpatients with chronic HF, lower UNa+ was associated with a higher risk of recurrent WHF events.

Challenges of estimating treatment effects after a positive interim analysis

BackgroundThis research investigates why a beneficial treatment effect reported at the first interim analysis (IA) may diminish at a subsequent analysis (SA). We examined three challenges in interpreting treatment effects from randomized clinical trials (RCTs) after the first positive IA: overestimation bias; non-proportional hazards; and heterogeneity in recruitment. We investigate how a penalized estimation method can address overestimation bias, and discuss additional factors to consider when interpreting positive IA results. MethodsWe identified oncology RCTs reporting positive results at the initial IA and a SA for event-free (EFS) and overall survival (OS). We modeled: (1) the hazard ratio at IA (HRIA) versus its timing as measured by the information fraction (IF; i.e., events at IA versus total events sought); and (2), the ratio of HRIA to HRSA (rHR) versus the IF. This was repeated for HRIA adjusted for overestimation bias. Examples of the other two challenges were sought. ResultsAmongst 71 RCTs, HRIA were positively associated with the IF (slope: EFS 0.83, 95 % CI 0.44–1.22; OS 0.25, 95 % CI 0.10–0.41). HRIA tended to exaggerate HRSA, and more so the lower the IF (slope rHR versus IF: EFS 0.10, 95 % CI − 0.22 to 0.42; OS 0.26, 95 % CI 0.07–0.46). Adjusted HRIA did not exaggerate HRSA (slope rHR versus IF: EFS − 0.14, 95 % CI − 0.67 to 0.39; OS 0.02, 95 % CI − 0.26 to 0.30). Examples of two other challenges are shown. ConclusionOverestimation bias, non-proportional hazards, and heterogeneity in recruitment and other important treatments should be considered when communicating estimates of treatment effects from positive IAs.

Efficacy and safety of the serratus anterior plane block (SAP block) for pain management in patients with multiple rib fractures in the emergency department: a retrospective study.

Chest trauma is a severe and frequent cause of admission to the emergency department (ED). The serratus anterior plane (SAP) block seems to be an effective method of pain management; however, data on efficacy and safety of a single SAP block performed in the ED by emergency physicians (EP) are limited. This study aimed to compare SAP block performed by the EP in the ED plus standard therapy to standard therapy alone in terms of pain severity at 0-3-6-12-18 and 24h, total opioid consumption (milligrams of morphine equivalents, MME), respiratory function (SpO2/FiO2 ratio), and adverse events (i.e. pneumothorax, infections in the site of injection, or Local Anaesthetic Systemic Toxicity syndrome due to SAP block) in the first 24h. This retrospective, monocentric study included adult patients admitted to the Sub-intensive Care Unit (SICU) of the ED with multiple rib fractures between 01/2022 and 03/2023. 156 patients (65.4% male; median age 62 years; median injury severity score 16; median thoracic trauma severity score 8) were included. 75 (48.2%) underwent SAP block. Patients undergoing SAP block showed significantly less pain 3-6-18h after a single block, required less MME (0 [0-20] vs. 20 [0-40], p < 0.001), showed higher SpO2/FiO2 ratio, and no adverse events were reported. The SAP block, in combination with standard therapy, appeared to be more effective in providing pain relief than standard therapy alone in patients admitted to the SICU for traumatic rib fractures.

Effect of empagliflozin on total myocardial infarction events by type and additional coronary outcomes: insights from the randomized EMPA-REG OUTCOME trial

BackgroundThe effect of empagliflozin, a sodium-glucose-co-transporter-2 inhibitor, on risk for myocardial infarction has not been fully characterized.MethodsThis study comprised prespecified and post-hoc analyses of the EMPA-REG OUTCOME trial in which 7020 people with type 2 diabetes (T2D) and cardiovascular disease [mostly atherosclerotic (ASCVD)] were randomized to empagliflozin or placebo and followed for a median 3.1 years. We assessed the effect of empagliflozin on total (first plus recurrent) events of centrally adjudicated fatal and non-fatal myocardial infarction (MI) using a negative binomial model with robust confidence intervals (CI) that preserves randomization and accounts for the within-patient correlation of multiple events. Post hoc, we analyzed types of MI: type 1 (related to plaque-rupture/thrombus), type 2 (myocardial supply–demand imbalance), type 3 (sudden-death related, i.e. fatal MI), type 4 (percutaneous coronary intervention-related), and type 5 (coronary artery bypass graft-related). MIs could be assigned to > 1 type.ResultsThere were 421 total MIs (including recurrent); 299, 86, 26, 19, and 1 were classified as type 1, 2, 3, 4, and 5 events, respectively. Overall, empagliflozin reduced the risk of total MI events by 21% [rate ratio for empagliflozin vs. placebo, 0.79 (95% CI, 0.620–0.998), P = 0.0486], largely driven by its effect on type 1 [rate ratio, 0.79 (95% CI, 0.61–1.04)] and type 2 MIs [rate ratio, 0.67 (95% CI, 0.41–1.10)].ConclusionsIn T2D patients with ASCVD, empagliflozin reduced the risk of MIs, with consistent effects across the two most common etiologies, i.e. type 1 and 2.Trail Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01131676.

Bifid triple viable preparation combined with enteral nutrition as a supportive treatment for acute ischemic stroke: a systematic review and meta-analysis.

The benefits and risks of bifid triple viable preparations in patients with acute ischemic stroke (AIS) are still controversial. This study aimed to assess the efficacy and safety of bifid triple viable preparations in combination with enteral nutrition for the management of AIS. Eight public databases including China National Knowledge Infrastructure, China Biology Medicine, VIP, WanFang, EBSCO, PubMed, Cochrane Library, and Web of Science were searched for relevant clinical literature, published through January 2024. These data were then used in the present meta-analysis. A total of 15 studies involving 1,544 patients were included in the meta-analysis. In terms of nutritional status, the results showed that compared with enteral nutrition alone, the bifid triple viable preparation combination group increased the levels of total protein (mean difference [MD], 5.53; 95%confidence interval [CI], 1.94-9.12; p = 0.003), albumin (MD, 4.01; 95%CI, 2.96-5.06; p < 0.00001), prealbumin (MD, 23.08; 95%CI, 16.22-29.95; p < 0.00001), hemoglobin (MD, 9.31; 95%CI, 6.34-12.27; p < 0.00001), and transferrin (MD, 0.64; 95%CI, 0.23-1.05; p = 0.002); in terms of neurological function, it improved the Glasgow Coma Scale (MD, 2.09; 95%CI, 0.69-3.49; p = 0.003), National Institute of Health Stroke Scale (MD, -3.07; 95%CI, -3.73 to -2.40; p < 0.00001), and Neurological Disability Score (MD, -6.68; 95%CI, -7.29 to -6.08; p < 0.00001); in terms of intestinal barrier function, it reduced the levels of endotoxin (MD, -0.55; 95%CI, -0.71 to -0.39; p < 0.00001), D-lactic acid (MD, -3.17; 95%CI, -4.07 to -2.26; p < 0.00001), diamine oxidase (MD, -4.39; 95%CI, -6.20 to -2.57; p < 0.00001), and endothelin (MD, -21.35; 95%CI, -27.86 to -14.83; p < 0.00001); in terms of immune function, it increased the levels of immunoglobulin G (MD, 1.01; 95%CI, 0.20-1.82; p = 0.01) and immunoglobulin M (MD, 0.16; 95%CI, 0.02-0.30; p = 0.03). Additionally, it reduced the incidence of pulmonary infection, vomiting, constipation, and diarrhea, while there were no significant differences in total adverse events, abdominal distension, anorexia, reflux, gastrointestinal bleeding, or electrolyte disturbance. The addition of bifid triple viable preparation to enteral nutrition improved the nutritional status, neurological function, intestinal barrier function, and immune function of patients with AIS, and reduced the risk of infection and gastrointestinal events.

Venous Thromboembolism Prophylaxis Should Be Recommended for Antepartum Admissions and Cesarean Delivery if Age and Body Mass Index are Greater Than 35.

Venous thromboembolism (VTE) is a major cause of maternal morbidity and mortality. Current expanded treatment recommendations result in the inclusion of a large percentage of the obstetric population, which has limited their adoption. The purpose of this study was to identify a population at high risk for VTE, with minimal impact on the number of patients that would qualify for expanded treatment. We performed a retrospective analysis of a large obstetric population. International Classification of Diseases, 10th Revsion (ICD-10) codes for VTE were used to identify patients presenting for obstetric or postpartum (PP) care from January 2016 to March 2018. The review focused on high-risk factors (history of VTE or high-risk thrombophilia), antepartum hospital admissions that were >72 hours in the previous 30 days, use of sequential compression devices, body mass index (BMI; kg/m2), age, and mode of delivery. Pharmacologic treatment efficacy was set at 90, 75, or 50%. During the 27-month review period, there were 120,235 deliveries and 93 had a VTE event in the index pregnancy or within 4 weeks PP (7.7/10,000 births). A history of VTE or high-risk thrombophilia was seen in 25.8% of cases. Antepartum admission was noted in 40.9%, and the combination of cesarean delivery (CD) with age and BMI ≥35 (Age + BMI + CD) was noted in 17.3% of PP cases. Targeting these latter two groups for VTE prophylaxis with a 75% efficacy suggests that 34% of the VTE events would likely have been prevented while increasing the total population treated by approximately 2%. Expanding pharmacologic prophylactical coverage to include an antepartum admission of >72 hours and those with Age + BMI + CD would result in about a one-third reduction in total VTE events with about 2% requiring treatment. These data support some of the suggested recommendations for expanded pharmacological deep venous thrombosis prophylaxis. · CD, and BMI and age >35 are high-risk factors for VTE.. · Antepartum admission >72 hours is a high-risk factor for VTE.. · Targeting antepartum admissions, CD, and BMI and age >35 would reduce VTE events by about 33%..

Clinical Outcomes of Collagenase Injections in Management of Dupuytren Contracture of the Proximal Interphalangeal Joint

Dupuytren contracture is characterized by the formation of cords and nodules in the palm. Surgical release has historically been the definitive treatment. Collagenase clostridium histolyticum (CCH) has been used successfully as an alternative to surgery. The treatment of proximal interphalangeal (PIP) contractures is the most challenging. The purpose of this study was to evaluate CCH treatment for Dupuytren contracture of the PIP joint. A retrospective chart review was performed for CCH treatment of Dupuytren contracture at a single institution from January 2010 to April 2023. Data collected included pretreatment/posttreatment total flexion contracture and adverse events. Contractures were analyzed both by severity (high >40° and low <40°) and type (isolated PIP; combined metacarpophalangeal and PIP). A total of 304 patients with 470 PIP joints treated were included. Digits with isolated and combined contractures each had an average pre-CCH treatment contracture of 51 (±23) degrees. Postmanipulations the contractures were 6 (±13) and 7 (±16) degrees, respectively. Clinical success (<5° residual contracture) and improvement (>50% correction of contracture) were associated with low severity contractures at postmanipulation. There were 256 adverse events recorded (54.5%), including 187 skin tears (39.8%), 68 cases of lymphadenopathy (14.5%), and one injection site infection (0.2%). High severity and combined contractures were independently associated with an increased incidence of skin tears upon manipulation. Collagenase clostridium histolyticum treatment is effective for isolated or combined PIP joint contractures. Adverse events were associated with more severe contractures. Given the degree of improvement based on contracture severity, earlier intervention may provide better correction of contracture. Therapeutic III.

Assessing morinidazole for surgical site infection in class III wounds prevention: a multi-centre, randomized, single-blind, parallel-controlled study

Surgical site infections are significant postoperative risks, antibiotic prophylaxis is crucial due to the presence of anaerobic bacteria. This study investigated the efficacy and safety of a novel nitroimidazole, morinidazole, in SSI reduction in class Ⅲ wounds, as there is currently a lack of evidence in the existing literature. A multicenter randomized clinical trial was conducted from December 2020 to October 2022 in the general surgery departments of 12 tertiary hospitals in China. 459 patients in two treatment groups using morinidazole plus ceftriaxone or ceftriaxone alone. Efficacy and safety were evaluated including SSI incidence, adverse events, and compliance. Statistical analysis employed SAS 9.4 software. Data analysis was performed from February to May 2023. A total of 440 participants (median [IQR] age, 63.0 [54.0, 70.0] years; 282 males [64.09%]; 437 patients were of Han race [99.32%]) were randomized. The experimental group exhibited a significantly lower SSI rate compared with the control group (31 [14.49%] vs 52 [23.01%]; risk difference, 1.76%, 95%CI, 1.08% to 2.88%; P=0.0224). The superficial incisional site infections revealed a marked reduction in the experimental group (12 [5.61%] vs 31 [13.37%]; risk difference,2.68%; 95%CI,1.34%to5.36%; P=0.0042). Non-surgical site infections, severe postoperative complications, and total adverse events showed no statistically significant differences between the groups (P>0.05). The significant decrease in SSI rates and superficial incisional infections demonstrates morinidazole as a valuable prophylactic antibiotic. Our findings provided valuable insights for clinical practice, where this new-generation nitroimidazole can play a crucial role in SSI prevention.

Results of the COMPASS Trial Analyzed Using Win Ratio Compared With Conventional Analytic Approaches

BackgroundWin ratio (WR) is a newer analytic approach for trials with composite end points that accounts for the relative importance of individual components. Our objective was to compare the results of the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial analyzed using WR with those obtained using conventional statistical approaches. MethodsWe used an unmatched WR analysis for first and total (first plus recurrent) events to examine effects of rivaroxaban with aspirin and rivaroxaban alone vs aspirin alone on primary efficacy (cardiovascular death, stroke, myocardial infarction), safety (modified International Society on Thrombosis and Haemostasis major bleeding), and net clinical benefit (primary efficacy plus fatal or critical organ bleeding) end points. We compared the WR results with those obtained using the Cox proportional hazards regression model for first events and Anderson-Gill method for total events. We calculated the win difference to estimate absolute treatment effects. ResultsThe WR approach produced results consistent with those obtained using conventional statistical methods for the primary composite end point (first event: WR, 1.32 [95% confidence interval (CI), 1.14-1.52]; 1/Cox hazard ratio, 1.32 [95% CI, 1.16-1.52]; total [first plus recurrent] events: WR, 1.32 [95% CI, 1.14-1.52]; 1/Anderson-Gill hazard ratio, 1.32 [95% CI, 1.16-1.54]) as well as for main safety and net clinical benefit end points. The absolute benefits of the combination of rivaroxaban and aspirin compared with aspirin alone calculated using the win difference were greatest in those with multiple high-risk features. ConclusionsReanalysis of the COMPASS trial results using WR produced results that were consistent with those obtained using conventional statistical approaches. Clinical Trial RegistrationNCT01776424

Deep Inspiration Breath Hold in Left-Sided Breast Radiotherapy: A Balance Between Side Effects and Costs

BackgroundDeep inspiration breath hold (DIBH) is an effective technique for reducing heart exposure during radiotherapy for left-sided breast cancer. Despite its benefits, cost considerations and its impact on workflow remain significant barriers to widespread adoption. ObjectivesThis study aimed to assess the cost-effectiveness of DIBH and compare its operational, financial, and clinical outcomes with free breathing (FB) in breast cancer treatment. MethodsTreatment plans for 100 patients with left-sided breast cancer were generated using both DIBH and FB techniques. Dosimetric data, including the average mean heart dose, were calculated for each technique and used to estimate the cardiotoxicity of radiotherapy. A state-transition microsimulation model based on SCORE2 (Systematic Coronary Risk Evaluation) algorithms projected the effects of DIBH on cardiovascular outcomes and quality-adjusted life-years (QALYs). Costs were calculated from a provider perspective using time-driven activity-based costing, applying a willingness-to-pay threshold of €40,000 for cost-effectiveness assessment. A discrete event simulation model assessed the impacts of DIBH vs FB on throughput and waiting times in the radiotherapy workflow. ResultsIn the base case scenario, DIBH was associated with an absolute risk reduction of 1.72% (95% CI: 1.67%-1.76%) in total cardiovascular events and 0.69% (95% CI: 0.67%-0.72%) in fatal cardiovascular events over 20 years. Additionally, DIBH was estimated to provide an incremental 0.04 QALYs (95% CI: 0.05-0.05) per left-sided breast cancer patient over the same time period. However, DIBH increased treatment times, reducing maximum achievable throughput by 12.48% (95% CI: 12.36%-12.75%) and increasing costs by €617 per left-sided breast cancer patient (95% CI: €615-€619). The incremental cost-effectiveness ratio was €14,023 per QALY. ConclusionsDespite time investments, DIBH is cost-effective in the Belgian population. The growing adoption of DIBH may benefit long-term cardiovascular health in breast cancer survivors.

Early Menarche as a Protective Factor Against Cardiovascular Events: A Systematic Review and Meta-analysis.

Women are often neglected in cardiovascular health prevention. Age at menarche (AAM) has been linked to cardiovascular (CVD) disease in women and is potentially identified as one of the significant CVD risk factor. However, there is still limited comprehensive evidence addressing this issue. This systematic review and meta-analysis aimed to investigate how early menarche affects the outcome of all-cause mortality, CVD mortality, total cardiovascular disease event, stroke (ischemic, hemorrhagic, and total stroke), and coronary heart disease (CHD). The Cochrane Library, MEDLINE, Embase, ScienceDirect, and Google Scholar databases were searched from March 2013 to March 2023 for cohorts investigating the effect of early onset of menarche on CVD events with a minimum follow-up period of 5 years. Studies that observed specific population and/or included women with a history of CVD at baseline were excluded. The Newcastle-Ottawa scale was used for risk of bias assessment for each cohort included. The data were presented as dichotomous measure using risk ratios. I2 statistics were utilized to evaluate the heterogeneity of presented data. Thirteen cohorts included 18 626 799 female patients with ages ranging from 43 to 62.6 years. These reported 6 estimates each for CHD (5 483 298 patients) and all-cause mortality (1 595 878 patients), 5 estimates each for total stroke (2 941 321 patients) and CVD mortality (1 706 742 patients), 4 estimates each for total CVD events (3 988 311 patients) and ischemic stroke (2 434 580 patients), and 1 estimate for hemorrhagic stroke (66 104 patients). Our study found that events of CHD were significantly lower in early menarche (RR 0.57; 95% CI 0.41-0.78; P <.00001), as well as total stroke (RR 0.51; 95% CI 0.35-0.73; P =.0003), CVD mortality (RR 0.47; 95% CI 0.22-0.98; P =.04), total CVD events (RR 0.44; 95% CI 0.25-0.76; P =.003), ischemic stroke (RR 0.31; 95% CI 0.15-0.61; P <.0008), and hemorrhagic stroke (RR 0.12; 95% CI 0.07-0.20; P <.00001); and insignificantly higher in all-cause mortality (RR 0.90, 95% CI 0.76-1.06, P =.20). In our study, cardiovascular events are lower in women with early menarche; hence, the later age of menarche is a potential risk factor to be considered when assessing CVD risk in a patient. However, our sample characteristics were heterogenous, and we did not consider other female hormonal factors that might potentially contribute to the CVD outcomes observed; thus, further studies are needed to clarify.

Variable soil moisture responses to rainfall events in fields under different management practices

AbstractSoil moisture response to rainfall is a key factor that dictates how well a landscape can support crop growth as well as its susceptibility to water runoff and leaching, however, few studies have investigated how agricultural management impacts this important soil function. This study compares two common agricultural soil treatments (cover crops and soil compaction) and their soil moisture response to rainfall in comparison to a control. In a humid temperate climate during March to November, individual rainfall events were delineated over two growing seasons and corresponding soil moisture responses were identified using in situ soil moisture sensors at four soil depths (20, 30, 40, and 60 cm). Results suggest that hydrological responses differed with both event type and management treatment. Not all rainfall events triggered a response: those that triggered responses at shallower soil depths were typically characterized by higher total event rainfall, and higher maximum and average rainfall intensity. In contrast, rainfall events triggering responses at deeper soil depths were characterized by longer event duration as well as higher 10‐day antecedent rainfall (AR). Soil moisture responses for the cover crop treatment were characterized by relatively lower initial and peak soil moisture at shallower depths but higher values at 60 cm depth, whereas soil moisture responses for the control and compacted soil treatments demonstrated the opposite. Matrix flow was most often generated for rainfall events with high magnitude and was not preferentially associated with any particular soil treatment. However, specific conditions were needed to generate vertical preferential flow, namely high total event rainfall for both horizons, or high AR for preferential flow in the Ap horizon, or high rainfall intensity for preferential flow in the Bt horizon. Our findings demonstrate the potential for detailed event‐based soil water process analysis using high‐frequency, multi‐depth soil moisture data.

Field measurement of entrapped pore‐air pressure and the effect of rising groundwater level in the soil layer

AbstractUnsaturated soil contains pore air, some of which becomes entrapped in the soil layer during the infiltration process. Such entrapped pore air in the soil layer inhibits infiltration, decreases hydraulic conductivity, and causes erroneous estimates of groundwater response. Experimental studies suggest an effect of compressed entrapped pore air on stream discharge. However, few studies have investigated the behaviour of pore air in the field, and no method for measurement of pore‐air behaviour has been established. We measured pore‐air pressure (Pair) with a simple handmade probe, combined with atmospheric pressure (Patm) and groundwater level. The entrapment and compression of pore air were detected based on the pressure difference (ΔP = Pair – Patm). Observations were conducted for approximately 1 year in two small headwater catchments (TC and HA, which have differences in soil depth and groundwater level dynamics) in Ibaraki Prefecture, Japan. Positive responses of ΔP during some rainfall events were confirmed at both TC and HA. Pore‐air entrapment occurred even during weak rainfall events with rainfall intensity of &lt;10 mm/h. During a typhoon event in October 2019, a maximum ΔP of 3.9 kPa was observed at HA. The pore pressure increase recorded by the tensiometer was mostly explained by the increase in ΔP, which was supported by the soil moisture data. Therefore, we concluded that our handmade measurement system could successfully measure Pair and detect pore‐air entrapment in the field. This showed that Pair is not negligible. Total event rainfall was related to the maximum ΔP. It also showed that the rise in the groundwater level plays a significant role in pressurization of the entrapped pore air. We present the first field data demonstrating the effect of groundwater level rise on the pressurization of entrapped Pair.