Balanced Cohort Research Articles

Examining 1-year mortality risk among patients with malignant melanoma undergoing immune checkpoint inhibitor therapy with a history of cannabis use.

11046 Background: Cannabis use has become an increased topic of discussion in the United States due to rise in legalization, thereby increasing its accessibility for recreational and medicinal use in diseases like cancer. Immune Checkpoint Inhibitor (ICI) therapy has also recently been increasing in patient with metastatic cancers such as melanoma by targeting PD1 or PD-L1 receptors to manipulate the body’s immune response to induce cancer cell death. Cannabis is mediated in part by the CB1 and CB2 receptors in the endocannabinoid system that is present in the natural immune system. Due to the body’s immune response to cannabis, it is hypothesized this could interfere with the activity of ICI therapy. However, research examining this is sparse. Therefore, the goal was to assess mortality in malignant melanoma patients with a history of cannabis use who undergo ICI therapy. Methods: A retrospective cohort study was performed with TriNetX, a federated database of ~100 million patients across 84 healthcare organizations. Patients >17 years from 2012-2023 were identified based on ICI-therapy initiation within 1 month of malignant melanoma diagnosis. Cohorts were then created by history of those with and without cannabis use disorder. 1:1 propensity score matching was conducted to control for confounding comorbidities and demographics. Unadjusted and adjusted hazard ratios (aHR) with 95% CI were calculated for 1-year mortality after therapy initiation. HR’s were estimated using the Cox proportional hazard model. Survival curves were compared using the log-rank test. Results: A total 14589 melanoma patients who underwent ICI therapy were identified, of which 2.3% had documented cannabis use disorder. Prior to matching, melanoma patients with cannabis history had a statistically significant higher 1-year mortality compared to those with no cannabis history (HR [95%CI] = 1.29 [1.04,1.6], log rank test: p=0.0197). After matching, two balanced cohorts of 344 patients remained and adjusting for confounders revealed that melanoma patients with cannabis history had no significant difference in 1-year mortality risk compared to patients without cannabis history (1.18 [0.87,1.6], log rank test: p=0.293). Conclusions: Cannabis use among melanoma patients was shown to not have any meaningful difference in 1-year mortality risk compared to patients without cannabis use history while undergoing ICI-therapy. Additional studies, such as examining cannabis frequency and dosage, is warranted to further examine its effect.

Examining the risk of immune checkpoint inhibitor-related toxicity among patients with melanoma and their history of cannabis use.

e21539 Background: With cannabis use rising due to better availability for recreational and medicinal uses, there is a need for studies examining cannabinoids interactions. Immune Checkpoint Inhibitors have been increasing in popularity among metastatic cancer patients like those with melanoma. The biological impact of cannabis is mediated in part by the CB1 and CB2 receptors present in the endocannabinoid system that is present in the immune system. ICI therapy also targets the immune system through manipulating PD-1/PD-L1 receptors to induce cancer cell death. Therefore, concurrent cannabis use with ICI therapy could have potentiating effects on toxicities and negatively impact efficacy. There is limited information in the literature examining this and therefore the goal was to examine the impact of ICI toxicity risk among melanoma patients on any form of ICI therapy. Methods: A retrospective cohort study was conducted using TriNetX, a multicenter database comprised of ~100 million patients across 84 healthcare organizations. Adults ( > 17 years) from 2012-2023 were identified based on ICI-therapy initiation within 1 month of malignant melanoma diagnosis. Patients were then stratified by history of those with and without cannabis use disorder. ICI toxicity categories were determined a priori and included cardiac, nephrological, gastrointestinal, endocrine, respiratory, ocular, hematological, hepatological, musculoskeletal, and neurological toxicities. 1:1 propensity score matching was conducted to control for comorbidities and demographics. Adjusted hazard ratios (aHR) with 95% CI were calculated at 1-year follow-up after therapy initiation for ICI toxicities between the cohorts. aHR was estimated using the Cox proportional hazard model. Results: A total 14589 melanoma patients who underwent ICI therapy were identified where 2.3% had history of cannabis use. Matching revealed two balanced cohorts of 344 patients. Melanoma patients with a history of cannabis use did not have any significant differences with controls for cardiotoxicity (aHR[95%CI] = 0.94[0.54,1.6]), Nephrotoxicity (0.86[0.51,1.5]), GI toxicity (1.44[0.95,2.2]), endocrine toxicity (1.2[0.82,1.8]), respiratory toxicity (0.93[0.55,1.6]), ocular toxicity (0.63[0.25,1.6]), hematologic toxicity (1.04[0.7,1.6]), neurotoxicity (1.04[0.6,1.7]), liver toxicity (1.41[0.78,2.5]), or musculoskeletal toxicity (1.53[0.62,3.8]). Conclusions: With cannabis use rising due in part to recreational use and in part to medical marijuana, the implications of use must be a topic of research. Cannabis use among melanoma patients did not provide any significant differences in risk of developing ICI-therapy-related toxicities. Additional studies are needed to validate this finding.

Adolescent and Adult Transitions From Major Depressive Disorder to Bipolar Disorder

Bipolar disorder (BD) often first appears in adolescence after onset of major depressive disorder (MDD), but diagnosis and treatment are commonly delayed. This delay is a concern because untreated BD is associated with adverse long-term outcomes, a more recurrent disease course and difficult-to-treat illness, and suicide attempts and deaths. To examine the association of age at MDD onset with early transition to BD and the subsequent use of psychiatric inpatient services as a severity indicator. This retrospective cohort study analyzed comprehensive data sourced from the Stockholm MDD Cohort data from 1997 to 2018, which encompass both outpatient and inpatient care. Individuals with an initial MDD episode from January 1, 2010, to December 31, 2013, who transitioned to BD by December 31, 2018, were identified. Data were analyzed between September 5 and December 28, 2023. Post MDD assessments included a depression severity index, comorbidities, psychotherapy, psychotropic drugs, and electroconvulsive therapy. The main outcome was the transition from MDD to BD, dichotomized as occurring early (within 3 years of MDD onset) or late (3 years after MDD onset). Secondary outcomes encompassed the use of psychiatric inpatient services post transition and patterns of medication usage. A robust propensity score matching framework was used to estimate outcomes. The final balanced cohort included 228 individuals, with an equal distribution between adults (n = 114; mean [SD] age, 24.5 [6.3] years; 96 female [84.2%]; 20 experiencing an early transition to BD [17.5%]) and youths (n = 114; mean [SD] age, 15.3 [1.6] years; 93 female [81.6%]; 8 experiencing an early transition to BD [7.0%]). Youths were substantially less likely to transition early (odds ratio, 0.42; 95% CI, 0.20-0.88; P = .02), despite having more outpatient visits (mean [SD] visits per month, 1.21 [1.07] vs 0.97 [0.98] for adults; P = .01). Both groups experienced substantially reduced inpatient care following a BD diagnosis, concurring with a marked decline in antidepressant use without increased lithium use. These findings suggest that adolescents may experience delayed BD progression and that diagnosis substantially reduced inpatient care in all age groups, which coincided with a reduction in the use of antidepressants. These findings may inform pharmacologic strategies in patients with first-episode MDD at risk for BD.

Safety of Combined Statin and Fibrate Therapy: Risks of Liver Injury and Acute Kidney Injury in a Cohort Study from the Shizuoka Kokuho Database.

Statins and fibrates are important means of preventing cardiovascular diseases, particularly when administered in combination as part of various therapeutic strategies. In this study, we explored the risks associated with various combinations of these drugs. We aimed to evaluate the risk of 1-year hospitalization with acute kidney injury, liver injury, pancreatitis, or rhabdomyolysis related to the concurrent administration of statins and fibrates. We performed a retrospective cohort study using data from the Shizuoka Kokuho Database, focusing on patients prescribed statins, fibrates, or a combination. Four drug exposure patterns were evaluated: adding statins to fibrates (exposure 1), switching from fibrates to statins (exposure 2), adding fibrates to statins (exposure 3), and switching from statins to fibrates (exposure 4). Hospitalization for the specified conditions within 1year was the outcome. Propensity score matching was used to create balanced cohorts for comparison. We studied 269,226 statin users and 16,282 fibrate users. After propensity score matching, there were 498 participants in the group of exposure 1, matched with 2988 in the fibrate-only group; 1180 in the group of exposure 2, matched with 7080 in the fibrate-only group; 1183 in group of exposure 3, matched with 11,830 in the statin only group; and 1356 in group of exposure 4, matched with 13,560 in the statin only group. The 1-year hospitalization rate with liver injury was higher in the group of exposure 1 than in the fibrate-only group (1.2% vs 0.3%, p < 0.01), in the group of exposure 2 than in the fibrate-only group (0.9% vs 0.3%, p < 0.01), and in the group of exposure 4 than in the statin-only group (0.6% vs 0.2%, p = 0.02). There was also a higher risk of 1-year hospitalization with acute kidney injury in group of exposure 1 than in the fibrate-only group (1.3% vs 0.3%, p = 0.01) but not in evaluations of exposure 2, 3, and 4. However, there were no differences in the risks of 1-year hospitalization with pancreatitis or rhabdomyolysis among the matched groups. We have demonstrated higher risks of 1-year hospitalization with liver injury or acute kidney injury associated with the use of combinations of statins and fibrates. This underscores the need for a cautious approach to the prescribing of such drug combinations and the importance of monitoring patients for potential adverse events.

The association between ondansetron use and mortality risk of traumatic brain injury patients: a population-based study.

Traumatic brain injury (TBI) patients suffer high risks of mortality. Ondansetron has been verified to be effective in improving the prognosis of some kinds of critically ill patients. We design this study to explore whether ondansetron use is associated with lower risks of mortality among TBI patients. TBI patients from the Medical Information Mart for Intensive Care-III were collected. The usage of ondansetron, including intravenous injection and oral tablet, since admission to the Beth Israel Deaconess Medical Center between 2001 and 2012 was identified. Univariate and multivariate logistic regression were performed to analyze the relationship between the ondansetron use and mortality of TBI patients. Propensity score matching (PSM) was utilized to generate balanced cohorts of the non-ondansetron use group and ondansetron use group. Sub-group analysis was performed to verify the association between the ondansetron use and mortality of TBI patients in different TBI severity levels after PSM. In TBI cohorts before PSM, the usage incidence of ondansetron was 37.2%. The 30-day mortality was significantly lower in the ondansetron group (p < 0.001). The multivariate logistic regression showed that ondansetron was associated with the lower mortality of TBI patients (p = 0.008). In TBI cohorts after PSM, the 30-day mortality of the ondansetron group was lower than that of the non-ondansetron group, although without statistical significance (p = 0.079). Logistic regression indicated ondansetron use was significantly associated with the lower mortality of moderate-to-severe TBI (p < 0.001) but not mild TBI (p = 0.051). In addition, Cox regression also presented that ondansetron use was significantly associated with the lower mortality of moderate-to-severe TBI (p < 0.001) but not mild TBI (p = 0.052). Ondansetron usage is associated with a lower mortality risk of moderate-to-severe TBI but not mild TBI patients. Ondansetron may be a novel adjunctive therapeutic strategy to improve the prognosis of moderate-to-severe TBI patients.

Comparison of the short-term outcomes between Y-incision aortic annular enlargement and traditional aortic annular enlargement techniques.

The short-term efficacy and safety of the Y-incision technique of aortic annular enlargement (AAE) has been established. We aimed to determine how the short-term outcomes of the Y-incision technique compared to traditional AAE techniques. From February 2011 to June 2022, 380 patients at the University of Michigan Hospital underwent aortic valve replacement (AVR) with AAE using either traditional annular enlargement techniques (Traditional group, n=270), including Nicks [63% (171/270)], Manouguian [34% (91/270)], and others [3% (8/270)], or the Y-incision technique (Y-incision group, n=110). Propensity score matching was performed by controlling for age, sex, body surface area (BSA), hypertension, diabetes, dialysis, chronic lung disease, stroke, prior cardiac surgery, primary indication, operative status, concomitant procedures, and prosthesis type, to generate a balanced cohort of 103 pairs. There were no differences in demographics, comorbidities, primary indications of the operations, or concomitant procedures between the matched groups. The median native aortic annulus diameter, measured in the operating room, was 21 mm for both groups. Median prosthesis size was 23 in the Traditional group, and 27 in the Y-incision group (P<0.001). There were no differences in perioperative complications/outcomes between the matched groups, including operative mortality, which was 3.9% (8/206) overall. Short-term survival was similar between the groups on Kaplan-Meier analysis; one-year survival was 95% in the Traditional group, and 97% in the Y-incision group (P=0.54). The Y-incision group had significantly lower mean aortic valve gradients (7 vs. 10 mmHg, P<0.001), larger aortic valve areas (2.2 vs. 1.8 cm2, P=0.007), and less moderate/severe patient-prosthesis mismatch (PPM) (5.5% vs. 23%, P=0.039) on one-year follow-up echocardiography. The Y-incision technique was as safe and more effective in enlarging the aortic annulus and upsizing the prosthetic valve than the traditional techniques of AAE in AVR for small aortic annuli.

Burden of Neurologic Health Care and Incident Neurologic Diagnoses in the Year After COVID-19 or Influenza Hospitalization.

Following the outbreak of viral infections from the severe acute respiratory syndrome coronavirus 2 virus in 2019 (coronavirus disease 2019 [COVID-19]), reports emerged of long-term neurologic sequelae in survivors. To better understand the burden of neurologic health care and incident neurologic diagnoses in the year after COVID-19 vs influenza, we performed an analysis of patient-level data from a large collection of electronic health records (EMR). We acquired deidentified data from TriNetX, a global health research network providing access to EMR data. We included individuals aged 18 years or older during index event, defined as hospital-based care for COVID-19 (from April 1, 2020, until November 15, 2021) or influenza (from 2016 to 2019). The study outcomes were subsequent health care encounters over the following year for 6 neurologic diagnoses including migraine, epilepsy, stroke, neuropathy, movement disorders, and dementia. We also created a composite of the 6 diagnoses as an incident event, which we call "incident neurologic diagnoses." We performed a 1:1 complete case nearest-neighbor propensity score match on age, sex, race/ethnicity, marital status, US census region patient residence, preindex years of available data, and Elixhauser comorbidity score. We fit time-to-event models and reported hazard ratios for COVID-19 vs influenza infection. After propensity score matching, we had a balanced cohort of 77,272 individuals with COVID-19 and 77,272 individuals with influenza. The mean age was 51.0 ± 19.7 years, 57.7% were female, and 41.5% were White. Compared with patients with influenza, patients with COVID-19 had a lower risk of subsequent care for migraine (HR 0.645, 95% CI 0.604-0.687), epilepsy (HR 0.783, 95% CI 0.727-0.843), neuropathies (HR 0.567, 95% CI 0.532-0.604), movement disorders (HR 0.644, 95% CI 0.598-0.693), stroke (HR 0.904, 95% CI 0.845-0.967), or dementia (HR 0.931, 95% CI 0.870-0.996). Postinfection incident neurologic diagnoses were observed in 2.79% of the COVID-19 cohort vs 4.91% of the influenza cohort (HR 0.618, 95% CI 0.582-0.657). Compared with a matched cohort of adults with a hospitalization or emergency department visit for influenza infection, those with COVID-19 had significantly fewer health care encounters for 6 major neurologic diagnoses over a year of follow-up. Furthermore, we found that COVID-19 infection was associated with a lower risk of an incident neurologic diagnosis in the year after infection.

Comparing survival outcomes between neoadjuvant and adjuvant chemotherapy within T2N1M0 stage hormone receptor-positive, HER2-negative breast cancer: a retrospective cohort study based on SEER database

BackgroundGuideline recommendations for the application of neoadjuvant chemotherapy (NACT) in T2N1M0 stage hormone receptor-positive, HER2-negative (HR + /HER2-) breast cancer are ambiguous. The debate continues regarding whether NACT or adjuvant chemotherapy (ACT) offers superior survival outcomes for these patients.Materials and MethodsFemale patients diagnosed with HR + /HER2- breast cancer at T2N1M0 stage between 2010 and 2020, were identified from the Surveillance, Epidemiology, and End Results database and divided into two groups, the NACT group and the ACT group. Propensity score matching (PSM) was utilized to establish balanced cohorts between groups, considering baseline features. Kaplan–Meier (K-M) analysis and the Cox proportional hazards model were executed to assess the efficacy of both NACT and ACT in terms of overall survival (OS) and breast cancer-specific survival (BCSS). A logistic regression model was employed to examine the association between predictive variables and response to NACT.ResultsAfter PSM, 4,682 patients were finally included. K-M curves showed that patients receiving NACT exhibited significantly worse OS and BCSS when compared with patients undergoing ACT. Multivariable Cox analysis indicated that not achieving pathologic complete response (non-pCR) after NACT (versus ACT), was identified as an adverse prognostic factor for OS (HR 1.58, 95% CI 1.36–1.83) and BCSS (HR 1.70, 95% CI 1.44–2. 02). The logistic regression model revealed that low tumor grade independently predicted non-pCR.ConclusionAmong T2N1M0 stage HR + /HER2- patients, OS and BCSS of NACT were inferior to ACT. Patients who attained non-pCR after NACT demonstrated significantly worse survival outcomes compared with those who received ACT.

Effects of Administration and Intensity of Statins on Mortality in Patients Undergoing Hemodialysis.

(1) Background: Few studies have investigated the association between the intensity of statins and patient survival rates in patients undergoing hemodialysis (HD) as primary outcomes. This study aimed to evaluate patient survival rates according to the intensity of statins using a large sample of patients undergoing maintenance HD. (2) Methods: Data from a national HD quality assessment program were used in this study (n = 53,345). We divided the patients into four groups based on the administration and intensity of statins: Group 1, patients without a prescription of statins (n = 37,944); Group 2, patients with a prescription of a low intensity of statins (n = 700); Group 3, patients with a prescription of a moderate intensity of statins (n = 14,160); Group 4, patients with a prescription of a high intensity of statins (n = 541). (3) Results: Significant differences in baseline characteristics were observed among the four groups. Group 1 had the best patient survival among the four groups in the univariate Cox regression analyses. However, multivariable Cox regression analyses showed that the patient survival rate was higher for Group 3 than for Group 1. Cox regression analyses using data of a balanced cohort showed that, on univariate analyses, the HRs were 0.93 (95% CI, 0.91-0.95, p < 0.001) in Group 2 and 0.95 (95% CI, 0.93-0.96, p < 0.001) in Group 3 compared to that in Group 1. Group 4 had a higher mortality rate than Groups 2 or 3. The results from the cohort after balancing showed a similar trend to those from the multivariable Cox regression analyses. Young age and less comorbidities in Group 1 were mainly associated with favorable survival in Group 1 in the univariate analysis using cohort before balancing. Among the subgroup analyses based on sex, age, presence of diabetes mellitus, and heart disease, most multivariable analyses showed significantly higher patient survival rates in Group 3 than for Group 1. (4) Conclusions: Our study exhibited significant differences in baseline characteristics between the groups, leading to limitations in establishing a robust association between statin intensity and clinical outcomes. However, we conducted various statistical analyses to mitigate these differences. Some results, including multivariable analyses controlling for baseline characteristics and analyses of a balanced cohort using propensity score weighting, indicated improved patient survival in the moderate-intensity statin group compared to non-users. These findings suggest that moderate statin use may be associated with favorable patient survival.

Brentuximab vedotin and chemotherapy in relapsed/refractory Hodgkin lymphoma: a propensity score–matched analysis

AbstractSeveral single-arm studies have explored the inclusion of brentuximab vedotin (BV) in salvage chemotherapy followed by autologous stem cell transplantation (ASCT) for relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). However, no head-to-head comparisons with standard salvage chemotherapy have been performed. This study presents a propensity score–matched analysis encompassing individual patient data from 10 clinical trials to evaluate the impact of BV in transplant-eligible patients with R/R cHL. We included 768 patients, of whom 386 were treated with BV with or without chemotherapy (BV cohort), whereas 382 received chemotherapy alone (chemotherapy cohort). Propensity score matching resulted in balanced cohorts of 240 patients each. No significant differences were observed in pre-ASCT complete metabolic response (CMR) rates (P = .69) or progression free survival (PFS; P = .14) between the BV and chemotherapy cohorts. However, in the BV vs chemotherapy cohort, patients with relapsed disease had a significantly better 3-year PFS of 80% vs 70%, respectively (P = .02), whereas there was no difference for patients with primary refractory disease (56% vs 62%, respectively; P = .67). Patients with stage IV disease achieved a significantly better 3-year PFS in the BV cohort (P = .015). Post-ASCT PFS was comparable for patients achieving a CMR after BV monotherapy and those receiving BV followed by sequential chemotherapy (P = .24). Although 3-year overall survival was higher in the BV cohort (92% vs 80%, respectively; P < .001), this is likely attributed to the use of other novel therapies in later lines for patients experiencing progression, given that studies in the BV cohort were conducted more recently. In conclusion, BV with or without salvage chemotherapy appears to enhance PFS in patients with relapsed disease but not in those with primary refractory cHL.

Prognosis Impact and Prediction of Trans-Radial Access Failure in Patients With STEMI, A Nationwide Observational Study

Trans-radial access (TRA) is the primary arterial approach for percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI). However, occasionally, a crossover to trans-femoral access is necessary due to unsuccessful TRA. The impact of failed TRA on the prognosis in STEMI patients and the utility of predictive models for TRA failure remains uncertain. Data from the Hungarian Myocardial Infarction Registry (January 2014 - December 2020) were analyzed. Primary endpoints were 1-year mortality and major adverse cardiovascular events (MACE). Propensity score (PS) matching was employed to create a balanced cohort for comparing successful and failed TRA. The impact of unsuccessful TRA on prognosis was evaluated using Cox regression analysis. Machine learning techniques were applied to predict TRA failure. The performance and the clinical applicability of the novel and prior prediction models were comprehensively evaluated. Out of 76,625 registered patients, 34,293 (69.8 ± 13.4 years, male/female: 21,893/12,400) underwent TRA (33,573) or failed TRA (720) PCI for STEMI. After PS-matching, in the unsuccessful TRA group, the risk of mortality (34.3% vs 22.5%, HR: 1.6, 95% CI: [1.3 – 2.0], p < 0.001) and MACE (37.4% vs 26.8%, HR: 1.5, 95% CI: [1.3 – 1.8], p < 0.001) were significantly higher. Door-to-balloon time did not differ significantly (p = 0.835). In predictive analysis, regularized discriminant analysis emerged as the most promising model, surpassing prior prediction models (AUC: 0.66, sensitivity: 0.32, specificity: 0.86). Nevertheless, GRACE 2.0 score demonstrated a remarkable performance (AUC: 0.65, sensitivity: 0.51, specificity: 0.73). This study underscores the pivotal role of successful TRA in enhancing outcomes in STEMI cases, advocating for its prioritization. The inability to conclude interventions via this approach is linked to a poorer prognosis, even in risk-adjusted analyses. Our findings indicate that prediction models utilizing clinical parameters do not outperform the established GRACE 2.0 algorithm, questioning their utility. In conclusion, the results emphasize the significance of TRA success and the continued relevance of the GRACE score in clinical decision-making to optimize patient outcomes.

Comparative effectiveness and mortality of colistin monotherapy versus colistin-fosfomycin combination therapy for the treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections: A propensity score analysis

BackgroundCarbapenem-resistant Enterobacteriaceae (CRE) infections pose a significant threat to global health due to limited treatment options and high mortality rates. Colistin-based regimens have emerged as a primary treatment approach, but the effectiveness and mortality outcomes of colistin monotherapy versus colistin-fosfomycin combination therapy remain uncertain. This study aims to compare the effectiveness and mortality of colistin monotherapy and colistin-fosfomycin combination therapy for CRE infections. Notably, our study is the first to undertake a comprehensive examination of the effectiveness and mortality outcomes between colistin monotherapy and colistin-fosfomycin combination therapy in the context of CRE infections. MethodsA retrospective cohort study was conducted using data from patients diagnosed with carbapenem-resistant Enterobacteriaceae (CRE) infections at Nakornping Hospital during 2015 to 2022. Inverse probability weighting (IPW) was employed to create balanced cohorts of patients receiving either colistin monotherapy or colistin-fosfomycin combination therapy. The primary outcome measure was treatment effectiveness, assessed by 30-day mortality. Secondary outcome measures included clinical response, mortality at the end of treatment, and microbiologic response. Univariate and multivariate logistic regression analysis were employed after applying propensity score weighting using inverse probability of weighting (IPW). ResultsA total of 220 patients were included in the analysis, with 67 receiving colistin monotherapy and 153 receiving colistin-fosfomycin combination therapy. Propensity score weighting using IPW balanced the baseline characteristics between the two groups. The effectiveness of treatment, as measured by 30-day mortality, was not significantly different between the colistin monotherapy group and the colistin-fosfomycin combination therapy group (adjusted odds ratio [aOR] = 1.51, 95% confidence interval [CI]: 0.60–3.78, p = 0.383). Similarly, no significant difference was observed in the mortality at the end of treatment between the two groups (aOR = 1.26, 95% CI: 0.55–2.90, p = 0.576). The clinical response (aOR = 1.48, 95% CI: 0.61–3.59, p = 0.383) and microbiologic response (aOR = 0.66, 95% CI: 0.18–2.38, p = 0.527) were similar between the colistin monotherapy and colistin-fosfomycin combination therapy groups. ConclusionThe propensity score analysis among 220 matched patients showed comparable treatment effectiveness and mortality between colistin monotherapy and colistin-fosfomycin combination therapy for CRE infections. These results suggest that colistin monotherapy may be as effective as combination therapy. More prospective randomized controlled trials are needed to confirm these findings and establish optimal CRE treatment strategies.

(127) Sexual Health Implications Associated with Psychotropic Medication Use Among Adolescents During the COVID-19 Pandemic

Abstract Introduction The use of psychotropic medications has a notable effect on sexual well-being. Prolonged use is closely linked to dyspareunia, reduced sexual desire, hypogonadism, and erectile dysfunction. We hypothesized that there was an increase in the prescription rates of psychotropic medications among adolescent patients during the COVID-19 pandemic due to the unprecedented stress experienced by isolated youth. Objective We examined the prescription rates of psychotropic medications and the simultaneous usage of PDE5 inhibitors in adolescent patients during the COVID-19 pandemic in order to compare usage of these medications prior to the pandemic. Methods To conduct our retrospective matched cohort study, we utilized data obtained from the TriNetX Research Network. The study focused on adolescent patients aged 10-19 presenting for outpatient evaluation, and were placed into two cohorts: 1) those evaluated before the COVID-19 pandemic, and 2) those evaluated during the pandemic. Patients with previous psychiatric diagnoses or prior use of psychotropic medications were excluded from the study. Our primary interest was to examine new prescription patterns within 90 days of the outpatient evaluation. To ensure balanced cohorts, propensity score matching was conducted using logistic regression, resulting in cohorts of equal size. Results A total of 1,612,283 adolescents pre-COVID-19 and 1,008,161 adolescents presenting during the COVID-19 pandemic for outpatient evaluations were identified. After propensity matching, a total of 1,005,408 adolescents were included in each cohort each with an average age of 14.7 ± 2.84 and 52% female and 48% male. Prescribing of antipsychotics and benzodiazepines were more frequent during the pandemic for adolescents (RR: 1.58, 95% CI 1.01-2.2). However, they were less likely to receive antidepressants (Risk Ratio (RR): 0.6, 95% Confidence Interval (CI) 0.57-0.63), anxiolytics (RR: 0.78, 95% CI 0.75-0.81), stimulants (RR: 0.26, 95% CI 0.25-0.27), as well as mood stabilizers (RR: 0.44, 95% CI 0.39-0.49). Erectile dysfunction requiring oral PDE5i in this cohort was more frequent during the pandemic for adolescents (RR: 1.53, 95% CI 1.05-2.01). Conclusions During the global COVID-19 pandemic, there was a notable rise in the prescription rates of antipsychotic and benzodiazepine medications compared to previous years. Interestingly, this increase aligned with a statistically significant rise in the prescription of PDE5 inhibitors (PDE5i) for treating erectile dysfunction. These findings indicate that clinicians need to be aware of the potential increased risk of medication-related sexual dysfunction among adolescents. Disclosure Yes, this is sponsored by industry/sponsor: NIH health grant RO1 DK130991 and Clinician Scientist Development Grant from the American Cancer Society. Clarification: Industry funding only - investigator initiated and executed study.

Vacuum assisted and gravitational venous drainage in aortic valve surgery: A propensity-match study.

Vacuum assisted venous drainage (VAVD) is widely adopted in minimally invasive cardiac surgery. VAVD enables the advantage of using smaller cannulae in a reduced surgical field while allowing satisfactory drainage and pump flow. The production of gaseous micro-emboli is a recognized risk associated with VAVD, however no difference in clinical endpoints have been reported between patients operated on with gravity venous drainage (GVD) or with VAVD. Due to the paucity of data on selected surgical populations, we sought to evaluate the early outcomes of patients undergoing isolated aortic valve replacement using VAVD or GVD. Data on 521 patients between 09/2016 and 09/2022 were retrieved from our internal database. Patients were divided into two groups according to use VAVD or GVD. A propensity match analysis was performed to account for difference between the two groups. The propensity match provided two well balanced cohorts with 129 patients each. A minimally invasive access was used in 97% of the cases in VAVD group vs 98% in GVD group (p = .68). Mean cardiopulmonary by-pass (CPB) time was 71 vs 73 min (p = .74), respectively. There was no difference in lactates peak (p = .19) and urine output during CPB (p = .74). We registered two in-hospital deaths in VAVD cohort (1.6%) vs. no mortality in GVD group (p = .5). Postoperative cerebral stroke occurred in 1 patient in GVD cohort vs. 0 in VAVD (p = 1). Severe postoperative acute kidney injury complicated the course in 16 patients in GVD group and in 5 patients who had VAVD (p = .012). VAVD was associated with a higher number of patients with elevated postoperative AST (p = .07) and Troponin I (p = .01) values. The use of VAVD during isolated aortic valve replacement was not associated with increased risks of postoperative complications and in-hospital mortality with results that were at least similar to those registered in a matched cohort of patients operated on with GVD.

Impact of Invasive Escherichia Coli Disease on Clinical Outcomes and Medical Resource Utilization Among Asian Patients in the United States.

Invasive Escherichia coli disease (IED) can lead to sepsis and death and is associated with a substantial burden. Yet, there is scarce information on the burden of IED in Asian patients. This retrospective study used US hospital data from the PINC AI™ Healthcare database (October 2015-March 2020) to identify IED cases among patients aged ≥ 60years. IED was defined as a positive E.coli culture in blood or other normally sterile body site (group1 IED) or positive culture of E.coli in urine with signs of sepsis (group2 IED). Eligible patients with IED were classified into Asian and non-Asian cohorts based on their reported race. Entropy balancing was used to create cohorts with similar characteristics. Outcomes following IED were descriptively reported in the balanced cohorts. A total of 646 Asian and 19,127 non-Asian patients with IED were included (median age 79years; 68% female after balancing). For both cohorts, most IED encounters had community-onset (> 95%) and required hospitalization (Asian 96%, mean duration 6.9days; non-Asian 95%, mean duration 6.8days), with frequent admission to intensive care (Asian 35%, mean duration 3.3days; non-Asian 34%, mean duration 3.5days), all standardized differences [SD] < 0.20. Compared to non-Asian patients, Asian patients were more likely to be discharged home (54% vs. 43%; SD = 0.22), and less likely to be discharged to a skilled nursing facility (24% vs. 31%; SD = 0.16). In-hospital fatality rates during the IED encounter were similar across cohorts (Asian 9%, non-Asian 10%; SD = 0.01). Most E.coli isolates showed resistance to ≥ 1 antibiotic (Asian 61%; non-Asian 64%) and 36% to ≥ 3 antibiotic classes (all SD < 0.20). IED is associated with a substantial burden, including need for intensive care and considerable mortality, in Asian patients in the USA that is consistent with that observed for non-Asian patients.

Platelet versus fresh frozen plasma transfusion for coagulopathy in cardiac surgery patients.

Platelets (PLTS) and fresh frozen plasma (FFP) are often transfused in cardiac surgery patients for perioperative bleeding. Their relative effectiveness is unknown. We conducted an entropy-weighted retrospective cohort study using the Australian and New Zealand Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database. All adults undergoing cardiac surgery between 2005-2021 across 58 sites were included. The primary outcome was operative mortality. Of 174,796 eligible patients, 15,360 (8.79%) received PLTS in the absence of FFP and 6,189 (3.54%) patients received FFP in the absence of PLTS. The median cumulative dose was 1 unit of pooled platelets (IQR 1 to 3) and 2 units of FFP (IQR 0 to 4) respectively. After entropy weighting to achieve balanced cohorts, FFP was associated with increased perioperative (Risk Ratio [RR], 1.63; 95% Confidence Interval [CI], 1.40 to 1.91; P<0.001) and 1-year (RR, 1.50; 95% CI, 1.32 to 1.71; P<0.001) mortality. FFP was associated with increased rates of 4-hour chest drain tube output (Adjusted mean difference in ml, 28.37; 95% CI, 19.35 to 37.38; P<0.001), AKI (RR, 1.13; 95% CI, 1.01 to 1.27; P = 0.033) and readmission to ICU (RR, 1.24; 95% CI, 1.09 to 1.42; P = 0.001). In perioperative bleeding in cardiac surgery patient, platelets are associated with a relative mortality benefit over FFP. This information can be used by clinicians in their choice of procoagulant therapy in this setting.

Thiamine use is associated with better outcomes for traumatic brain injury patients.

Traumatic brain injury (TBI) is a global health concern that often leads to poor prognosis. We designed this study to explore whether thiamine use is associated with a better prognosis of TBI. TBI patients selected from the Medical Information Mart for Intensive Care-III database were included in the study. Univariate and multivariate Cox regression analyses were performed to examine the relationship between thiamine use and mortality in TBI patients. Propensity score matching (PSM) was utilized to generate balanced cohorts of the non-thiamine use group and the thiamine use group. Subgroup analysis was performed in the cohort after PSM to verify the association between thiamine use and mortality in TBI patients across different stratifications. The incidence of thiamine use in TBI was 18.3%. The thiamine use group had a lower 30-day mortality rate (p < 0.001), a longer length of ICU stay (p < 0.001), and a longer length of hospital stay (p < 0.001) than the non-thiamine use group, both in the primary cohort before PSM and the cohort after PSM. A multivariate Cox regression analysis confirmed that thiamine use was independently associated with mortality (OR = 0.454, p < 0.001) after adjusting for confounding effects. In the cohort after PSM, the subgroup analysis showed that thiamine use is associated with lower mortality in TBI patients with a Glasgow Coma Scale (GCS) score of < 13, but it is not associated with mortality in TBI patients whose GCS score is ≥13. Thiamine supplementation is effective in improving the outcome of TBI, except in cases of mild TBI. The optimal thiamine supplementation strategy for TBI is worthwhile to be explored in future studies.

Association of Human Papillomavirus Vaccination with Risk for Rheumatoid Arthritis

Introduction: The potential association between Human papillomavirus (HPV) vaccination and the onset of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) remains a pivotal point of exploration in immunization safety discourse. Method: This retrospective cohort study aims to ascertain the risk of RA and JIA following HPV vaccination, utilizing the TriNetX database, tracking the health trajectories of 32,165,650 females, from January 1, 2013, to December 31, 2022. By applying inclusion and exclusion criteria, we formed a balanced cohort of 344,165 HPV-vaccinated individuals, the propensity score-matched 1:1 with unvaccinated controls based on a range of demographic and clinical parameters. This study used the Cox proportional hazards model to analyze the risk of RA and JIA after HPV vaccination, expressed the results by adjusted hazard ratio (aHR) and 95% confidence interval (CI), and used Kaplan-Meier survival analysis. Results: The analysis showed that over a follow-up period of up to 10 years after vaccination, the risks of RA and JIA were significantly reduced in the HPV vaccination group, with aHR of 0.428 (95% CI: 0.372-0.492) and 0.310 (95% CI: 0.262-0.367) respectively. This trend persisted in a sensitivity analysis that replaced the control group with influenza-vaccinated individuals. Subgroup analyses showed that the risk of RA and JIA was significantly reduced in the 9-18 and 19-26 age groups, across ethnic backgrounds, and in the obesity and asthma subgroups, but still among those with a smoking history, the risk reduction was not statistically significant. Conclusion: Our findings highlight the significant protective effect of the HPV vaccine against RA and JIA. Further research is needed to delve deeper into this molecular mechanism.

Curtailing infection risks in hepatitis C patients: the effect of antiviral treatment in revision shoulder arthroplasty

BackgroundRevision shoulder arthroplasty (RevSA) is a complex procedure that can result in various postoperative complications. However, the impact of hepatitis C virus (HCV) on postoperative complications after RevSA remains unclear due to limited and inconsistent evidence. This study aims (1) to investigate the incidence of postoperative complications in patients with HCV undergoing RevSA, and (2) to evaluate the impact of HCV treatment on complication rates at different time points after the revision procedure, specifically at 90 days, 1 year, and 2 years MethodsWe queried a national, all-payer database to investigate recent trends in the utilization of RevSA among HCV patients to assess postoperative complication rates, including venous thromboembolism, wound complication, transfusion, and prosthetic joint infection. Statistical analyses involved propensity score matching to create balanced cohorts and logistic regression to determine the relative risk of postoperative complications. "Data was analyzed with the SPSS Statistics software (version 24.0 for Windows; IBM, Armonk, NY, USA). The study included patients who underwent partial or total RevSA procedures between January 1, 2010, and December 31, 2020. Patients were identified based on medical claims that included procedural codes for RevSA and associated diagnosis codes for PJI or insertion/removal of an antibiotic spacer. A Bonferroni correction was utilized because many tests were performed and statistical significance was set at p=0.0125. ResultsThe HCV cohort demonstrated higher prosthetic joint infection (PJI) rates at one-year (5.5 vs 3.9%, p=0.006) and two-year follow-ups (6.7 vs 4.6%, p=0.006). However, no significant differences emerged in venous thromboembolism (VTE) and wound complications rates between the HCV and non-HCV cohorts. Comparing untreated and treated HCV patients, the former showed significantly higher PJI rates at two-year p=0.010, while the treated group had significantly lower odds ratios for PJI. When comparing treated HCV patients with the no HCV cohort, minimal differences were found in postoperative outcomes, indicating no significant difference in the risk of complications between the groups ConclusionOur study observed an association between HCV patients who received antiviral treatment prior to RevSA and a reduced incidence of PJI compared to untreated HCV patients. When comparing this group to the non-HCV controls, there was no significant difference in the incidence of PJI, suggesting a potential association between antiviral treatment and the observed risk patterns in HCV patients. Proper management of HCV-positive patients during RevSA is crucial for improving outcomes and reducing complications.

Radiomics of pericardial fat: a new frontier in heart failure discrimination and prediction

ObjectivesTo use pericardial adipose tissue (PAT) radiomics phenotyping to differentiate existing and predict future heart failure (HF) cases in the UK Biobank.MethodsPAT segmentations were derived from cardiovascular magnetic resonance (CMR) studies using an automated quality-controlled model to define the region-of-interest for radiomics analysis. Prevalent (present at time of imaging) and incident (first occurrence after imaging) HF were ascertained using health record linkage. We created balanced cohorts of non-HF individuals for comparison. PyRadiomics was utilised to extract 104 radiomics features, of which 28 were chosen after excluding highly correlated ones (0.8). These features, plus sex and age, served as predictors in binary classification models trained separately to detect (1) prevalent and (2) incident HF. We tested seven modeling methods using tenfold nested cross-validation and examined feature importance with explainability methods.ResultsWe studied 1204 participants in total, 297 participants with prevalent (60 ± 7 years, 21% female) and 305 with incident (61 ± 6 years, 32% female) HF, and an equal number of non-HF comparators. We achieved good discriminative performance for both prevalent (voting classifier; AUC: 0.76; F1 score: 0.70) and incident (light gradient boosting machine: AUC: 0.74; F1 score: 0.68) HF. Our radiomics models showed marginally better performance compared to PAT area alone.Increased PAT size (maximum 2D diameter in a given column or slice) and texture heterogeneity (sum entropy) were important features for prevalent and incident HF classification models.ConclusionsThe amount and character of PAT discriminate individuals with prevalent HF and predict incidence of future HF.Clinical relevance statementThis study presents an innovative application of pericardial adipose tissue (PAT) radiomics phenotyping as a predictive tool for heart failure (HF), a major public health concern. By leveraging advanced machine learning methods, the research uncovers that the quantity and characteristics of PAT can be used to identify existing cases of HF and predict future occurrences. The enhanced performance of these radiomics models over PAT area alone supports the potential for better personalised care through earlier detection and prevention of HF.Key Points•PAT radiomics applied to CMR was used for the first time to derive binary machine learning classifiers to develop models for discrimination of prevalence and prediction of incident heart failure.•Models using PAT area provided acceptable discrimination between cases of prevalent or incident heart failure and comparator groups.•An increased PAT volume (increased diameter using shape features) and greater texture heterogeneity captured by radiomics texture features (increased sum entropy) can be used as an additional classifier marker for heart failure.