Secondary Outcome Analysis Research Articles

Cataract Surgery and Incidence of Retinal Vascular Occlusion: Population-Based Cohort Study Using a Target Trial Emulation Framework

BackgroundPrevious studies suggested an association between cataract surgery and retinal vascular occlusion. However, the association may be attributable to detection bias because postoperative monitoring may be more frequent for those who receive cataract surgery than for those who do not. DesignPopulation-based cohort study using target trial emulation framework. MethodsWe included patients with cataract aged 50 years and older receiving cataract surgery or non-surgical interventions identified from the Taiwan National Health Insurance Research Database between 2003 and 2018, matched by propensity score. The primary outcome was retinal vascular occlusion. Cox proportional hazards models were used to compare surgery and control groups. Additional analyses were restricted to patients who had undergone fundoscopic examination within 6 months prior to cataract surgery to address the issue of detection bias. ResultsWe included 577,129 cataract surgery and control pairs. We found the hazard ratio (HR) for retinal vascular occlusion after cataract surgery was 1.23 (95% confidence interval (CI): 1.17-1.29), compared with the control group. Secondary outcome analyses yielded similar results for retinal artery occlusion (HR: 1.13, 95% CI: 1.02-1.26) and retinal vein occlusion (HR: 1.26, 95% CI: 1.20-1.33). However, no risk of retinal vascular occlusion was observed among patients who had received fundoscopic examinations (HR: 1.06, 95% CI: 0.98-1.15) at baseline. ConclusionsOur study underscored the importance of conducting complete baseline fundoscopic examinations before cataract surgery to clarify whether postoperative conditions are due to patients’ underlying diseases or unintended complications of cataract surgery.

G-tube placement in patients with robin sequence undergoing mandibular distraction osteogenesis: A multi-institutional review

The goal of this study was to investigate the relationship between mandibular distraction osteogenesis (MDO) and rates of postoperative gastrostomy tube (G-tube) placement among patients with isolated and syndromic Robin sequence (RS). This study was a multi-institutional retrospective chart review of patients with RS who underwent MDO at one of three different pediatric tertiary medical centers. The primary aim of the study was to compare rates of G-tube placement following MDO among the three institutions. The primary outcome was analyzed using Fischer's exact test. The secondary aim of the study was to assess for other contributing factors to G-tube placement such as demographic differences, length of hospital stay, and age at MDO. Analysis of secondary outcomes was assessed using multiple logistic regression models. A total of 125 patients met the inclusion criteria, which required RS diagnosis, completion of MDO between 2004 and 2019, and adequate medical record availability. Sixty percent (n = 75) of subjects were categorized as isolated RS (iRS) and forty percent (n = 50) as syndromic RS (sRS). After MDO, 20% (n = 25) of all patients had G-tubes placed. Of the iRS group, 14.7% (n = 11) required a G-tube, while 28% (n = 14) of the sRS group required a G-tube. The post-operative G-tube rate was similar between institutions when considering all patients. When considering only those patients with iRS, the post-MDO G-tube rate at one center was significantly higher than the other two. Overall, most patients with RS did not require a G-tube after MDO, regardless of diagnosis. However, the significant differences in rates of G-tube placement among patients with iRS may indicate differing practice philosophies, surgical protocols, thresholds for G-tube placement, or regional influences between institutions.

The traditional Chinese medicine Qiliqiangxin in heart failure with reduced ejection fraction: a randomized, double-blind, placebo-controlled trial

Previous findings have indicated the potential benefits of the Chinese traditional medicine Qiliqiangxin (QLQX) in heart failure. Here we performed a double-blind, randomized controlled trial to evaluate the efficacy and safety of QLQX in patients with heart failure and reduced ejection fraction (HFrEF). This multicenter trial, conducted in 133 hospitals in China, enrolled 3,110 patients with HFrEF with NT-proBNP levels of ≥450 pg ml−1 and left ventricular ejection fraction of ≤40%. Participants were randomized to receive either QLQX capsules or placebo (four capsules three times daily) alongside standard heart failure therapy. The trial met its primary outcome, which was a composite of hospitalization for heart failure and cardiovascular death: over a median follow-up of 18.3 months, the primary outcome occurred in 389 patients (25.02%) in the QLQX group and 467 patients (30.03%) in the placebo group (hazard ratio (HR), 0.78; 95% confidence interval (CI), 0.68−0.90; P < 0.001). In an analysis of secondary outcomes, the QLQX group showed reductions in both hospitalization for heart failure (15.63% versus 19.16%; HR, 0.76; 95% CI, 0.64−0.90; P = 0.002) and cardiovascular death (13.31% versus 15.95%; HR, 0.83; 95% CI, 0.68−0.996; P = 0.045) compared to the placebo group. All-cause mortality did not differ significantly between the two groups (HR, 0.84; 95% CI, 0.70−1.01; P = 0.058) and adverse events were also comparable between the groups. The results of this trial indicate that QLQX may improve clinical outcomes in patients with HFrEF when added to conventional therapy. ChiCTR registration: ChiCTR1900021929.

Hypothermic oxygenated perfusion of the donor heart in heart transplantation: the short-term outcome from a randomised, controlled, open-label, multicentre clinical trial

Static cold storage (SCS) remains the gold standard for preserving donor hearts before transplantation but is associated with ischaemia, anaerobic metabolism, and organ injuries, leading to patient morbidity and mortality. We aimed to evaluate whether continuous, hypothermic oxygenated machine perfusion (HOPE) of the donor heart is safe and superior compared with SCS. We performed a multinational, multicentre, randomised, controlled, open-label clinical trial with a superiority design at 15 transplant centres across eight European countries. Adult candidates for heart transplantation were eligible and randomly assigned in a 1:1 ratio. Donor inclusion criteria were age 18-70 years with no previous sternotomy and donation after brain death. In the treatment group, the preservation protocol involved the use of a portable machine perfusion system ensuring HOPE of the resting donor heart. The donor hearts in the control group underwent ischaemic SCS according to standard practices. The primary outcome was time to first event of a composite of either cardiac-related death, moderate or severe primary graft dysfunction (PGD) of the left ventricle, PGD of the right ventricle, acute cellular rejection at least grade 2R, or graft failure (with use of mechanical circulatory support or re-transplantation) within 30 days after transplantation. We included all patients who were randomly assigned, fulfilled inclusion and exclusion criteria, and received a transplant in the primary analysis and all patients who were randomly assigned and received a transplant in the safety analyses. This trial was registered with ClicalTrials.gov (NCT03991923) and is ongoing. A total of 229 patients were enrolled between Nov 25, 2020, and May 19, 2023. The primary analysis population included 204 patients who received a transplant. There were no patients who received a transplant lost to follow-up. All 100 donor hearts preserved with HOPE were transplantable after perfusion. The primary endpoint was registered in 19 (19%) of 101 patients in the HOPE group and 31 (30%) of 103 patients in the SCS group, corresponding to a risk reduction of 44% (hazard ratio 0·56; 95% CI 0·32-0·99; log-rank test p=0·059). PGD was the primary outcome event in 11 (11%) patients in the HOPE group and 29 (28%) in the SCS group (risk ratio 0·39; 95% CI 0·20-0·73). In the HOPE group, 63 (65%) patients had a reported serious adverse event (158 events) versus 87 (70%; 222 events) in the SCS group. Major adverse cardiac transplant events were reported in 18 (18%) and 33 (32%) patients in the HOPE and SCS group (risk ratio 0·56; 95% CI 0·34-0·92). Although there was not a significant difference in the primary endpoint, the 44% risk reduction associated with HOPE was suggested to be a clinically meaningful benefit. Post-transplant complications, measured as major adverse cardiac transplant events, were reduced. Analysis of secondary outcomes suggested that HOPE was beneficial in reducing primary graft dysfunction. HOPE in donor heart preservation addresses the existing challenges associated with graft preservation and the increasing complexity of donors and heart transplantation recipients. Future investigation will help to further elucidate the benefit of HOPE. XVIVO Perfusion.

Preventable sources of bias in subgroup analyses and secondary outcomes of randomized trials

BackgroundRandomized controlled trials are the gold standard for determining treatment efficacy in medicine. To deter harmful practices such as p-hacking and hypothesizing after the results are known, any analysis of subgroups and secondary outcomes must be documented and pre-specified. However, they can still introduce bias (and routinely do) if they are not treated with the same consideration as the primary analysis. MethodsWe describe several sources of bias that affect subgroup and secondary outcome analyses using published randomized trials and causal directed acyclic graphs (DAGs). ResultsWe use the RECOVERY and START trials to elucidate sources of bias in analyses of subgroups and secondary outcomes. Chance imbalance can occur if the distribution of prognostic variables is not sought for any given subgroup analysis as for the main analysis. This differential distribution of prognostic variables can also occur in analyses of secondary outcomes. Selection bias can occur if the subgroup variable is causally related to staying in the trial. Given loss to follow up is not normally addressed in subgroups, attrition bias can pass unnoticed in these cases. In every case, the solution is to take the same considerations for these analyses as we do for primary analyses. ConclusionsApproval of treatments and clinical decisions can occur based on results from subgroup or secondary outcome analyses. Thus, it is important to give them the same treatment as primary analyses to avoid preventable biases.

Operative versus Nonoperative Treatment of Proximal Hamstring Avulsions

BackgroundOperative treatment is widely used for acute proximal hamstring avulsions, but its effectiveness compared with that of nonoperative treatment has not been shown in randomized trials.MethodsIn this noninferiority trial at 10 centers in Sweden and Norway, we enrolled patients 30 to 70 years of age with a proximal hamstring avulsion in a randomized trial and a parallel observational cohort. Treatments were operative reinsertion of the tendons or nonoperative management. The primary end point was the Perth Hamstring Assessment Tool (PHAT) at 2 years of follow-up. Secondary outcomes included scores on the Lower Extremity Functional Scale (LEFS).ResultsA total of 119 patients were enrolled in the randomized trial and 97 patients in the observational cohort. In the per-protocol analysis of the randomized trial, the mean (±standard deviation) PHAT scores were 79.9±19.5 and 78.5±19.4 in the operative and nonoperative groups, respectively (PHAT scores range from 0 to 100, with higher scores indicating higher function). The prespecified noninferiority limit of 10 points was not crossed (mean difference, −1.2; 95% confidence interval [CI], −8.6 to 6.2; P=0.009 for noninferiority). Analyses of secondary outcomes, including a mean difference in the LEFS score of −1.6 (95% CI, −5.2 to 2.0), aligned with the primary outcome. The observed numbers of adverse events in the randomized trial were nine in the operative group versus three in the nonoperative group (odds ratio, 0.3; 95% CI, 0.1 to 1.2). In the analysis of the observational cohort, the mean PHAT score difference between the nonoperative and operative treatment groups was −2.6 (95% CI, −9.9 to 4.6).ConclusionsIn patients 30 to 70 years of age with proximal hamstring avulsions, nonoperative treatment was noninferior to operative treatment. (Funded by Afa Försäkring and others; ClinicalTrials.gov number, NCT03311997.)

Effects of concurrent aerobic and strength training in women diagnosed with non-metastatic breast cancer: a systematic review and meta-analysis.

To investigate the potential impact of concurrent aerobic and strength training (CT) on women diagnosed with breast cancer. Articles published in English and indexed in the PubMed, Web of Science, SPORTDiscus, The Cochrane Library, PsycINFO, EMBASE, and CINAHL Plus databases from their inception to 12 December 2023 were searched. Eligible studies were randomized controlled trials that involved CT and assessed cardiorespiratory fitness, cancer-related fatigue, and quality of life (QoL) using specialized tools. Subgroup analyses were conducted as per treatment status and characteristics. Risk of bias was evaluated with the Cochrane risk-of-bias tool (RoB 2.0). This study included 29 studies involving 2071 participants. CT was found to significantly improve patients' cardiorespiratory fitness (weighted mean difference = 4.24mL/kg/min, 95% confidence interval (CI) = 1.93-6.55, P < 0.001), cancer-related fatigue (standardized mean difference (SMD) = - 0.74, 95% CI = - 1.05 to - 0.44, P < 0.001), and QoL (SMD = 0.76, 95% CI = 0.50-1.01, P < 0.001). The analysis of secondary outcomes found that CT could significantly improve patients' body composition, anxiety, pain, sleep disorders, and anorexia and enhance upper and lower limb muscle strength, but was ineffective on depression. For women with breast cancer, CT significantly enhances cardiorespiratory fitness, alleviates cancer-related fatigue, and improves QoL. The health benefits of CT are inferior in the postmenopausal cohort compared to the overall study population. CT is advisable for female breast cancer survivors due to its significant effectiveness in mitigating cancer-related fatigue, enhancing cardiorespiratory fitness, and improving the QoL.

Outcome of Flexible Intramedullary Nailing versus Plating in Treatment of Diaphyseal Femur Fractures in Paediatrics: Systematic Review and Meta-analysis

Abstract Background Pediatric femoral fractures are the most the common long bone fracture in children, with one third of these occurring between ages 5 to 12. These injuries are usually the result of road traffic accidents, sports and non-accidental injury. Different modalities exist for managing these fractures, often stratified according to the age of the patient. Aim of the Work The aim of this work is to provide a complete overview of the optimal surgical treatment of diaphyseal femur fractures in children by evaluating and comparing the clinical and functional outcomes of flexible intramedullary nailing versus plating for such fractures. Patients and Methods This review followed the Cochrane Handbook's standard methodology and reported the findings in accordance with the Preferred Reporting Items for Systematic Reviews and Meta- analyses (PRISMA) statement guidelines. Result In patients undergoing flexible nailing, the surgical variable data found this treatment modality to be superior in terms of certain operative features: shorter operative duration times (p = 0.00001), smaller volumes of estimated blood loss (p = 0.00001). There was no difference regarding length of hostital stay (p = 0.59). This suggests that flexible nailing may offer increased safety to patients in terms of duration of anesthesia, volume of blood loss, and cost of surgery when compared to plating. However, Secondary outcome analysis also found a statistically significant increased risk of malunion (p = 0.002) and metalwork irritation (p = 0.00001) when using FIN compared to plating techniques. There was no difference regarding risk of infection (p = 0.53) and developing leg length discrepancy (p = 0.44). Conclusion Options for stabilization and fixation in this age group include flexible nailing, plating (open or sub-muscular), external fixation, or hybrid techniques.

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

To assess the comparative cardiovascular and renal effectiveness and safety of empagliflozin vs. dapagliflozin among patients with type 2 diabetes in routine clinical practice. Cohort study using data from nationwide registers in Sweden, Denmark, and Norway, from June 2014 to June 2021 included 141065 new users of empagliflozin and 58306 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. 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% confidence interval 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. Use of empagliflozin and dapagliflozin was associated with similar risk of cardiovascular and renal outcomes, mortality, and diabetic ketoacidosis.

Clinical Outcomes Following Operative and Nonoperative Management of Odontoid Fractures Among Elderly Individuals with Dementia.

The incidence of odontoid fractures among the elderly population has been increasing in recent years. Elderly individuals with dementia may be at increased risk for inferior outcomes following such fractures. Although surgical intervention has been maintained to optimize survival and recovery, it is unclear if this benefit extends to patients with dementia. We hypothesized that patients with dementia who were treated operatively for odontoid fractures would experience improved survival and lower rates of hospice admission but higher rates of delirium and of intensive interventions. We used Medicare claims data (2017 to 2018) to identify community-dwelling individuals with dementia who sustained type-II odontoid fractures. We considered treatment strategy (operative or nonoperative) as the primary predictor and survival as the primary outcome. The secondary outcomes consisted of post-treatment delirium, hospice admission, post-treatment intensive intervention, and post-discharge admission to a nursing home or a skilled nursing facility. In all models, we controlled for age, biological sex, race, Elixhauser Comorbidity Index, Frailty Index, admission source, treating hospital, and dual eligibility. Adjusted analyses for survival were conducted using Cox proportional hazards regression. Adjusted analyses for secondary outcomes were performed using generalized estimating equations. To address confounding by indication, we performed confirmatory analyses using inverse probability of treatment weighting. In this study, we included 1,030 patients. The median age of the cohort was 86.5 years (interquartile range, 80.9 to 90.8 years), 60.7% of the patients were female, and 90% of the patients were White. A surgical procedure was performed in 19.8% of the cohort. Following an adjusted analysis, patients treated surgically had a 28% lower hazard of mortality (hazard ratio, 0.72 [95% confidence interval (CI), 0.53 to 0.98]), but higher odds of delirium (odds ratio, 1.64 [95% CI, 1.10 to 2.44]). These findings were preserved in the inverse probability weighted analysis. We found that, among individuals with dementia who sustain a type-II odontoid fracture, surgical intervention may confer a survival benefit. A surgical procedure may be an appropriate treatment strategy for individuals with dementia whose life-care goals include life prolongation and maximizing quality of life in the short term following an injury. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Comparative Efficacy and Acceptability of Treatment Strategies for Antipsychotic-Induced Akathisia: A Systematic Review and Network Meta-analysis.

Antipsychotics are the treatment of choice for schizophrenia, but they often induce akathisia. However, comparative efficacy of treatment strategies for akathisia remains unclear. We performed a systematic review and network meta-analyses (PROSPERO CRD42023450720). We searched multiple databases on July 24, 2023. We included randomized clinical trials comparing 1 or more treatment strategies for antipsychotic-induced akathisia against each other or control conditions. We included adults with schizophrenia or other psychiatric disorders treated with antipsychotics. The primary outcome was akathisia severity at posttreatment. Secondary outcomes included akathisia response, all-cause dropout, psychotic symptoms, and long-term akathisia severity. We synthesized data in random effects frequentist network meta-analyses and assessed confidence in the evidence using CINeMA. We identified 19 trials with 661 randomized participants (mean age 35.9 [standard deviation 12.0]; 36.7% [195 of 532] women). No trials examined dose reduction or switching of antipsychotics. Findings suggested 5-HT2A antagonists (k = 6, n = 108; standardized mean difference [SMD] -1.07 [95% confidence interval, -1.42; -0.71]) and beta-blockers (k = 8, n = 105; SMD -0.46 [-0.85; -0.07]) may improve akathisia severity, but confidence in the evidence was deemed low. We also found that benzodiazepines (k = 2, n = 13; SMD -1.62 [-2.64; -0.59]) and vitamin B6 (k = 3, n = 67; SMD -0.99 [-1.49; -0.50]) might also be beneficial, but confidence in the evidence was very low. Analyses of secondary outcomes did not provide additional insights. Our findings suggest that 5-HT2A antagonists, beta-blockers, and with a lesser certainty, benzodiazepines, and vitamin B6 might improve akathisia. Given the low to very low confidence in the evidence of add-on agents and the absence of evidence of their long-term efficacy, careful consideration of side effects is warranted. These recommendations are extremely preliminary and further trials are needed.

Describing Intravenous Extravasation Injuries in Children (DIVE2 Study).

Extravasation is the erroneous delivery of IV medication or fluid into the extravascular space. Complications ranging from mild injury to amputation can result, depending on the physical and pharmacologic properties of the infusate. Children are at increased risk for extravasation injuries. There is a paucity of data on the treatment and outcomes of extravasation injuries, particularly in terms of the role of pharmacologic antidotes. To describe the incidence of extravasation at a tertiary pediatric care centre (as an update to a previous study), to identify the agents most commonly involved in extravasation injuries, to describe the antidotes used for management of injuries and their related adverse drug effects, and to describe complications related to injuries. The medical records of pediatric patients who experienced an extravasation injury at the BC Children's and BC Women's Hospitals, between September 1, 2008, and September 30, 2020, were reviewed. Data regarding management (adherence with institutional protocol) and outcomes of injuries were collected. The 242 charts included in the analysis noted a total of 245 extravasation injuries, for an extravasation incidence of 0.04% per patient-day. Of the 242 patients, 110 were excluded from secondary outcome analysis due to lack of data detailing the extravasation event. Of the remaining 132 patients, the majority were neonates (n = 54, 40.9%), infants (n = 33, 25.0%), and children (n = 34, 25.8%), and more than a third were treated on general pediatric wards (n = 50, 37.9%). The medications most frequently involved were total parenteral nutrition with lipids (36/132, 27.3%), vancomycin (36/132, 27.3%), and IV fluids (35/132, 26.5%). Most of the patients had mild outcomes and recovered without complications. No adverse drug events from antidotes were reported. The incidence of extravasation at the study institution remained low, with the medications involved being similar to those reported in the literature and the majority of patients having mild outcomes. Additional prospective studies are needed to assess the efficacy and safety of antidotes administered for extravasation injuries.

BCG vaccination is associated with longitudinal changes in systemic eicosanoid levels in elderly individuals: A secondary outcome analysis

We investigated how BCG vaccination affects the levels of certain eicosanoids, namely Leukotriene B4, 15-epimer of LXA4, prostaglandin F2, Lipoxin A4, Prostaglandin E2 and Resolvin D1 in the plasma of healthy elderly individuals (aged 60–80) before vaccination, one month post-vaccination (M1), and six months post-vaccination (M6). This study is part of the clinical trial "BCG Vaccine Study: Reducing COVID-19 Impact on the Elderly in Indian Hotspots," registered in the clinical trial registry (NCT04475302). While some primary outcomes have been previously reported, this analysis delves into the immunological outcomes. Our findings indicate that BCG vaccination leads to reduced plasma levels of 15-epi-LXA4, LXA4, PGE2, and Resolvin D1 at both M1 and M6. In contrast, there is a notable increase in circulating levels of LTB4 at these time points following BCG vaccination. This underscores the immunomodulatory effects of BCG vaccination and hints at its potential to modulate immune responses by dampening inflammatory reactions.

Interactive assistance via eHealth for small- and medium-sized enterprises’ employer and health care manager teams on tobacco control (eSMART-TC): A cluster randomized hybrid type II trial (N-EQUITY2101/J-SUPPORT2102).

10606 Background: Organizational commitment and consistent leadership are crucial to facilitate implementation of workplace wellness programs. We aimed to investigate whether interactive assistance for SME managers to implement tobacco control programs (compared with usual practice) would increase 6-month abstinence rates in tobacco-smoking employees. Methods: This hybrid type II cluster randomized effectiveness implementation trial was done in Japan. SMEs in the intervention group received interactive assistance to employers and health managers for 6 months by supporting employees through campaigns, tailored ongoing facilitation, and ensuring executive engagement and support, aiming to promote utilization of reimbursed smoking cessation treatments and implement smoke-free workplaces. SMEs in the control group received feedback on the results of the baseline survey and information on smoking cessation measures. Stratified randomization was used to allocate SMEs to either group. The primary outcome was salivary cotinine-validated 7-day point-prevalence abstinence rate at 6 months, and the key secondary outcome was the adoption score of the two recommended measures (promote smoking cessation standard treatment visits, and smoke-free policy) at each SME at 6 months (range: 0–2). Other secondary outcomes included implementation and process outcomes (e.g., proportion of smoking cessation treatment use). Results: Between July 1, 2021, and May 16, 2022, 38 SMEs enrolled. Twenty SMEs were randomly assigned to the intervention group and 18 SMEs to the control group. Among 2,929 employees enrolled, 2,556 responded the baseline survey (response rate: 87.3%; men 65.0%; mean age 44.8 years) and 713 of them (27.9%) indicated being a current smoker in the baseline. Then 176 (6.9%) were omitted because of missing primary outcome data (mainly owing to not responding, turnover, resignation, or retirement); therefore, 537 participants (21.0%) were included in the intention-to-treat based analyses of the primary outcome. At 6 months, the validated 7-day point-prevalence abstinence rate in the intervention group was significantly higher than that in the control group (11.2% vs 4.6%; difference = 6.6%, 95% confidence interval: 2.2%–11.1%, p=0.004). Regarding the analysis for key secondary outcomes, all randomized SMEs were included. At 6 months, adoption score of the two recommended measures was also significantly higher than that in the control group (1.5 vs 1.1; difference = 0.4, 95% confidence interval: 0.01–0.86, p=0.047). Conclusions: Interactive support for SME managers to implement tobacco control measures (compared with usual practice) can accelerate the implementation of evidence-based smoking cessation measures and significantly increase 6-month abstinence rates. Clinical trial information: UMIN000044526.

Risk of stroke in patients with atrial fibrillation and chronic lymphocytic leukemia.

e19030 Background: There has been a noticeable increase in the incidence of Atrial Fibrillation (AF) in patients with Chronic lymphocytic leukemia (CLL), especially patients treated with first-line therapy medications such as ibrutinib. However, these patients' risk of thromboembolic events is not well defined. Methods: Data for hospitalized patients with AF was obtained from The National Inpatient Sample (NIS) database from 2016-2018. Baseline risk factors were identified using ICD-10 codes. Patients who were already on anticoagulation were excluded. A logistic regression model was used to establish the relationship between variables and to adjust for underlying risk factors. The primary outcome was ischemic stroke between CLL and non-CLL patient cohorts. Results: The total number of patients was 1784456, out of which 1171644 patients were included in the study. There were 1165283 patients without CLL and 6361 with CLL. AF patients with CLL had more males (62.5% vs. 37.5%; P&lt;.001), were older (74.6 vs. 78.82; P&lt;.001), and had a lower prevalence of diabetes, hypertension, coronary artery disease, and hyperlipidemia. Pre-match analysis showed a lower rate of stroke in patients with AF and CLL compared to those without CLL (2.7% vs 4.2%; p&lt;0.001). Post-match analysis revealed similar results with a lower risk of strokes in patients with CLL (4% vs 2.7%; p&lt;0.001). Binary logistic regression analysis for primary and secondary outcomes revealed similar results pre-match and post-match. Patients who have AF and CLL had lower rates of stroke compared to those without CLL (OR: 0.647(0.530–0.790); p&lt;0.001). Conclusions: AF patients with CLL were associated with a lower risk of ischemic stroke compared to those without CLL despite a higher risk profile as assessed by traditional risk factors. These findings should be considered while making decisions for therapies for the prevention of thromboembolic events.

Sex differences among S-ICD recipients: a propensity-matched, multicenter, international analysis from the i-SUSI project

Abstract Background Women have been historically underrepresented in implantable cardioverter defibrillator (ICD) trials, despite sex differences in the epidemiology and clinical presentation of ventricular arrhythmias (VAs). So far, no data on sex differences among subcutaneous-ICD (S-ICD) recipients have ever been described. Purpose To investigate sex-related differences in patients undergoing S-ICD implantation. Methods Consecutive patients enrolled in the multicenter i-SUSI project were analyzed. The iSUSI (International SUbcutaneouS Implantable cardioverter defibrillator) is a multi-center, open-label, independent, and physician-initiated observational project, involving 22 Public and Private Healthcare Institutions from 5 different countries in Europe and in the US. Comparisons between sexes were performed using an adjusted analysis with 1:1 propensity matching for age, body mass index (BMI), left ventricular function (LVEF) and underlying myocardial substrate (ischemic vs non-ischemic cardiomyopathy). The primary outcome was the rate of appropriate shocks during follow-up. Inappropriate shocks and other device-related complications were deemed secondary outcomes. Results A total of 1698 patients were enrolled in the current project. Females represented the 23.5% (n=399) of the study cohort. After propensity matching, two cohorts of 374 matched patients with similar baseline characteristics served as the study cohort for this analysis (Figure 1, panel A). Despite similar procedural characteristics and a matched BMI, female S-ICD recipients had a lower calculated risk of ventricular arrhythmias conversion failure as per PRAETORIAN score (females at low-risk 73.4% vs males 81.3%, p=0.049). Over a median follow-up time of 26.5 [12.7–42.5] months (without differences between the two cohorts), n=68 (9.1%) patients experienced appropriate shocks and n=105 (14.0%) patients suffered from a device-related complication, including 75 (10.3%) cases of inappropriate shock therapy (Figure 1). Appropriate shocks were more common in the male cohort (rate/y 3.4% vs 1.7%; log-rank p=0.049), while no significant differences in device-related complications (rate/y: 6.3% vs 5.8%; log-rank p=0.595) and inappropriate shocks (rate/y: 4.3% vs 3.1% log-rank p=0.375) were observed among groups. Survival analysis for primary and secondary outcomes has been reported in Figure 1, panel B-C-D. At multivariate analysis, male sex remained significantly associated with the primary outcome of interest (aHR 1.591 CI 0.975–2.595, p=0.063). Conclusion In a large S-ICD registry, females were overall underrepresented. In a propensity-matched cohort of S-ICD recipients, women were less likely to experience appropriate ICD therapy, while not showing higher risk of device related-complications and inappropriate shocks. Despite similar BMI and peri-procedural characteristics, women showed a lower risk of conversion failure according to PRAETORIAN score.Figure 1

#1491 Management of immune thrombotic thrombocytopenic purpura without therapeutic plasma exchange

Abstract Background and Aims Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening autoimmune disorder caused by ADAMTS13 deficiency. The anti-VWF nanobody Caplacizumab is approved for iTTP treatment, reducing the need for therapeutic plasma exchange (TPE) and improving platelet recovery and survival. This study evaluates the treatment of acute iTTP with caplacizumab and immunosuppression, but without TPE, in comparison to the conventional management with TPE, caplacizumab and immunosuppression. Method All patients in this study were identified from the Austrian Thrombotic Microangiopathy Registry (ATMAR) and the German REACT-2020 TTP registry (ClinicalTrials.gov identifier: NCT04985318). A total of 42 acute iTTP episodes in 41 patients were managed with a treatment regimen aimed at avoiding first-line TPE if the platelet count increased after the first dose of 10 mg caplacizumab, and the patient's condition and organ function remained stable (TPE-free cohort). This treatment modification was implemented based on shared decision making. An extensive efficacy and safety analysis of this approach was performed, in comparison with a control group of 59 iTTP patients, receiving frontline caplacizumab treatment with TPE and immunosuppression (TPE cohort). The main outcome was time to platelet count normalization. Secondary outcomes included clinical response, exacerbation, refractoriness, and iTTP-related deaths. Results The primary outcome parameter, time to platelet count normalization, was not significantly different between TPE-free and TPE-based management (Kaplan-Meier estimator and log-rank test, Table 1 and Fig. 1). The median time to platelet count normalization was 3 days in the TPE-free cohort and 4 days in the TPE cohort. There were no significant differences in clinical response, exacerbations, refractoriness, or iTTP-related deaths. For evaluation of the short-term treatment response, both cohorts were assessed for the time to platelet count doubling. The median time to platelet count doubling was 1 day in both cohorts. Four patients in the TPE-free cohort did not immediately respond to the first caplacizumab injection and subsequently underwent TPE, after a maximum monitoring period of 40 hours. In these patients, TPE was initiated at a median of 1.5 days after the first caplacizumab dose, and TPE was performed for a median of 4.5 days. This delayed platelet response could be attributed to concomitant diseases and factors, e.g. active HIV and hepatitis B virus coinfection, active CMV infection, concomitant antiplatelet antibodies in association with an ovarian teratoma, and multiple platelet transfusions before the correct diagnosis. During overall follow-up, complications were observed in 11 patients (26.2%) in the TPE-free group and 16 patients (27.1%) in the TPE group, excluding complications of iTTP that were evaluated as outcome parameters. Serious complications occurred in 4 patients (6.8%) from the TPE cohort while on TPE, including severe systemic anaphylactic reactions with severe hypotension, generalized seizure and supraventricular tachycardia. Bleeding complications were reported without a significant difference between groups. Conclusion For the first time since the introduction of TPE in the early 1990s, the results of our study systematically challenge the absolute need for TPE and suggest a paradigm shift in acute iTTP management. In detail, our treatment approach was successfully implemented in 38 of 42 acute iTTP episodes (90.5%). We observed no significant difference in the time to platelet count normalization between patients with iTTP treated with and without TPE. The analysis of key secondary outcomes did not reveal significant differences in the proportion of patients who achieved a clinical response or experienced exacerbations, refractoriness, or TTP-related deaths. In conclusion, Caplacizumab and immunosuppression, without TPE, rapidly controlled microvascular thrombosis and achieved a sustained clinical response in iTTP.

Preterm Infants on Early Solid Foods and Neurodevelopmental Outcome-A Secondary Outcome Analysis of a Randomized Controlled Trial.

There are no evidence-based recommendations regarding the introduction of solid foods in preterm infants. The objective of this study was to investigate whether age at the introduction of solid foods affects neurodevelopmental outcomes. This study focuses on analyzing secondary outcomes from a prospective trial involving very low birth weight infants who were randomly assigned to either an early (10-12th week corrected age) or a late (16-18th week corrected age) complementary feeding group. The study evaluated neurodevelopmental outcomes at one and two years of corrected age, as well as at three years and four months of uncorrected age by utilizing Bayley scales. In total, 89 infants were assigned to the early and 88 infants to the late group, all with a mean gestational age of 27 + 1 weeks. A linear mixed-effects model was used to compare neurodevelopmental outcomes across the study groups, taking into account variables such as gestational age at birth, sex, nutrition at discharge, parents' highest education level, and high-grade intraventricular hemorrhage. The analysis did not reveal any significant differences between the groups. The timepoint of the introduction of solid foods had no impact on neurodevelopmental outcomes at one and two years of corrected age, and at three years and four months of uncorrected age.

The Incidence of Thyroid Cancer in Bethesda III Thyroid Nodules: A Retrospective Analysis at a Single Endocrine Surgery Center.

Fine-needle aspiration cytology (FNAC) is widely used to diagnose and monitor thyroid nodules. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is the standard for interpreting FNAC specimens. The risk of malignancy in Bethesda III nodules, also known as Atypia of Undetermined Significance (AUS), varies significantly throughout several studies published worldwide. This retrospective study examines the risk of cancer in thyroid FNAC categorized as Bethesda III as identified in the final histopathology of thyroidectomy specimens at a single endocrine surgery center. This retrospective cohort analysis included 1038 consecutive patients who underwent elective thyroid surgery with complete follow-up data between January 2020 and March 2024. Preoperative data on clinical and pathological characteristics have been collected. The final histopathology report from the thyroidectomy specimen was compared to the results of the preoperative FNAC on nodules that were judged to be Bethesda category III. Statistical methods were performed using SPSS version 29. A total of 670 ultrasound-guided FNACs (64.5%) performed during the study period were included in the final analysis. The study population was predominantly female, represented by 79.6% of patients with a mean age of 42.5 (SD 12.1), while 20.4% were male and significantly older with mean age of 45.13 years (p = 0.02). The FNAC inadequacy rate was 5.1%, which was associated with a high risk of malignancy (6 out of 34; 17.6%). Out of the total sample size of 170 patients classified as group III, 57 were found to have malignancies in final surgical histopathology, representing 33.5% of the cases within this category. The secondary gender-related outcome analysis showed that female patients classified under the Bethesda II category had a significantly higher risk of malignancy, with a rate of 21.2%, compared to males who had a malignancy rate of 3.4% in the same Bethesda category (p = 0.001, chi-square test). However, the female patients exhibited prognostically superior non-invasive tumors compared to male individuals (p = 0.02, chi-square test). This study's results indicate that Bethesda categories II and III are associated with a higher risk of malignancy in comparison to the reports of the first and third editions of the TBSRTC, particularly for female patients classified under category II.

Progression of adenomyosis: Rate and associated factors.

To evaluate the rate of disease progression and the factors associated with such progression in patients with an ultrasound diagnosis of adenomyosis. This was a single center, prospective, observational, cohort study performed at a tertiary referral center. Patients who obtained an ultrasound diagnosis of adenomyosis from May 2022 to August 2022 were recruited. Demographic, clinical and ultrasound data were recorded at the first visit (T0) and after 12 months (T1) for enrolled patients and compared between T0 and T1. The study population was divided in two groups according to progression (increase in uterine volume >20%) or stability/regression (decrease or increase in uterine volume ≤20%) of adenomyosis at T1. Primary study outcome was the rate of adenomyosis progression, while secondary study outcome was the association of adenomyosis progression with demographic and clinical factors. Post hoc subgroups analyses for primary and secondary study outcomes were performed based on hormonal therapy (untreated and treated). A total of 221 patients were enrolled in the study, with no significant difference in terms of baseline data among the two study groups and no patients were lost to follow-up. The overall rate of adenomyosis progression was 21.3% (47/221 patients). The rate was 30.77% in hormonally untreated women, and 18.34% in hormonally treated women. Progression was associated with the presence of focal adenomyosis of the outer myometrium (P = 0.037), moderate to severe dysmenorrhea (P = 0.001), chronic pelvic pain (P = 0.05), dyschezia (P = 0.05), and worsening of chronic pelvic pain (P = 0.04) at T1. Adenomyosis showed a rate of disease progression of 21.3% at the 12-month follow-up (30.77% in hormonally untreated women, and 18.34% in hormonally treated women). The presence and/or worsening of painful symptoms, such as severe dysmenorrhea, dyschezia and chronic pelvic pain, as well as the presence focal adenomyosis of the outer myometrium, might help identify patients at higher risk of disease progression and tailor their follow-up.