Outcome Of All-cause Mortality Research Articles

Rationale and design of the STOP-IMH randomised trial: Safety of ticagrelor monotherapy after primary percutaneous coronary intervention for ST-elevation myocardial infarction and the effect on intramyocardial haemorrhage

BackgroundTicagrelor monotherapy after 1–3 months of dual antiplatelet therapy (DAPT) has shown to be effective and safe after percutaneous coronary intervention (PCI), including in patients with an ST elevation myocardial infarction (STEMI). Direct omission of aspirin could further reduce bleeding complications and may reduce the incidence and expansion of intramyocardial haemorrhage (IMH), a frequent complication after revascularisation for a STEMI. MethodsThis multicentre open label pilot study randomises 200 STEMI patients within 24 hours after primary PCI and before the first subsequent dose of aspirin to ticagrelor monotherapy or ticagrelor plus aspirin for twelve months. As IMH is more frequently observed after an anterior STEMI, IMH and infarct size will be determined with cardiac magnetic resonance (CMR) imaging in 60 anterior STEMI patients. In this subgroup, blood samples will be analysed for biochemical outcomes. ResultsThe primary safety endpoint consists of major adverse cardiac and cerebral events, and the primary efficacy endpoint is infarct size on CMR. Secondary efficacy endpoints consist of the incidence and extent of IMH determined by CMR, and of clinical bleeding events. Other endpoints include all-cause mortality and biochemical outcomes. ConclusionThe STOP-IMH pilot study compares ticagrelor monotherapy with ticagrelor plus aspirin directly after primary PCI in 200 STEMI patients. We aim to provide a signal of safety regarding ischemic events for the direct omission of aspirin after primary PCI, and to compare the infarct size by CMR between the two treatment strategies in the first week after primary PCI.

Comparing Cryoprecipitate-Poor Plasma to Fresh Frozen Plasma as Replacement Therapy in Thrombotic Thrombocytopenic Purpura: an Updated Meta-Analysis

Cryoprecipitate-poor plasma (CPP) has been suggested as a promising alternative to the standard fresh frozen plasma (FFP) in plasma exchange therapy (TPE) for thrombotic thrombocytopenic purpura (TTP) given its lower concentrations of von Willebrand Factor (VWF). However, its efficacy and safety remain a topic of debate. We conducted a systematic review and meta-analysis comparing CPP to FFP during TPE in patients with TTP. PubMed, Embase, and Cochrane Central were systematically searched for studies reporting outcomes of all-cause mortality, relapse rate, response to treatment, and the mean number of TPE sessions. Sensitivity analyses restricted to randomized controlled trials (RCTs) were performed. Review Manager v5.4 and RStudio v4.1.2 were used for statistical analysis. The protocol was prospectively registered in PROSPERO (ID CRD42023440665). Eight studies, including three RCTs and five non-randomized studies, met the eligibility criteria. A total of 290 patients with TTP were included, of whom 144 (49.7%) received CPP and 146 (50.3%) received FFP. Use of CPP was associated with lower mortality (RR 0.41; 95% CI 0.23-0.72; p=0.002; I²=0%), while the subgroup analysis restricted to RCTs showed no statistical difference between groups (p=0.36). No significant differences were found in relapse rate, response to treatment, or mean number of TPE sessions between groups. Our findings show that the use of CPP is not inferior to FFP in TPE. Given the limited population, future clinical trials are needed to elucidate its benefits compared to FFP in patients with TTP.

205. Utilization of the Four Themes of the CDC/ATSDR SVI Interactive Map in Assessing Initial Clostridioides difficile Infection Outcomes

Abstract Background Social determinants of health (SDoH) (e.g., education, clean water, health care access) are external factors shown to impact health outcomes. Inequities in SDoH have been hypothesized to contribute to poorer Clostridioides difficile infection (CDI) outcomes. The Centers for Disease Control’s (CDC) Social Vulnerability Index (SVI) is a composite measure of neighborhood (census tract) based on four major themes: socioeconomic status (SES), housing characteristics (H&C), race/ethnicity (REM) status, and housing and transportation (H&T). There is a cessation of literature that describes the impact of each SVI theme on CDI outcomes. The objective of this study was to utilize the four themes of the CDC SVI to determine the impact of SDoH on initial CDI severity and all-cause mortality outcomes. Methods Adult patients admitted to Loma Linda University Medical Center (LLUMC) with an initial episode of CDI between January 2020 to June 2021 were included. Patient residential addresses were collected and input into the CDC/ATSDR SVI Interactive Map. Vulnerability groups were congregated into 2 main subgroups [patients with SVI scores of < 0.4999 are grouped as low vulnerability (LV) and patients with SVI scores of ≥ 0.5 are grouped as high vulnerability (HV)]. Results 206 patients were included, and those with an overall HV SVI score were more likely to have a higher all-cause mortality rate and to present with severe or fulminant initial CDI compared to those with a LV score. The frequency of initial severe CDI was 3x greater for the SVI themes of SES and H&C [61/206 (29.61%) vs 19/206 (9.22%)] in patients with a HV score compared to those with LV scoring. Further, patients who presented with an HV score for the H&T theme were more likely to present with initial severe (26.21% vs 12.62%) or fulminant CDI (13.11% vs 5.34%) versus those with a LV score. When considering the REM status theme, the initial fulminant CDI diagnosis was about 37x greater among individuals with a HV score (17.96% vs 0.49%) and mortality 9x greater when compared to those with LV scoring (8.74% vs 0.97%). Conclusion HV scores across SES, H&C, REM status, and H&T correlate with increased CDI severity and mortality rates. Further research and targeted interventions should be identified. Disclosures Anna Zhou, PharmD, Melinta Therapeutics: Honoraria Jacinda C. Abdul-Mutakabbir, PharmD, MPH, CSL Sequiris: Advisor/Consultant|CSL Sequiris: Honoraria|GSK: Advisor/Consultant|GSK: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria

P-873. Efficacy and Safety of Cefadroxil for Oral Transitional Therapy for Staphylococcal and Streptococcal Bloodstream Infections

Abstract Background Cefadroxil has a longer half-life and reduced clearance allowing for once or twice daily administration, making it an appealing alternative to cephalexin, which requires up to four times daily dosing. There has been increased interest in utilization of oral beta-lactams as oral transitional therapy for bloodstream infections (BSI) due to its favorable safety profile, however, there is currently limited data available evaluating cefadroxil for BSI. Methods A retrospective cohort study of adult patients hospitalized with MSSA or Streptococcal BSI from January 2022 to March 2024 and transitioned from IV to oral antibiotics was conducted. Patients were grouped by cefadroxil vs other highly bioavailable antibiotics (linezolid, TMP/SMX, fluoroquinolones) and compared for clinical outcomes of 30-day all-cause mortality, 30-day readmission, and 90-day recurrence. Results 103 patients were included (cefadroxil 40 patients vs other 63 patients). Overall, 79% were male, 69% were Hispanic, 33% had uncontrolled diabetes, and median CCI was 2. Clinical presentation was similar with median Pitt bacteremia score of 0 in both groups (p=ns). 56% were MSSA BSI, and the most common Strep spp. was Strep pyogenes (15%). The most common source of infection was an intermediate-risk source of infection (78%). Median days of lead in IV antibiotic therapy did not differ between groups (cefadroxil 5 vs other 6, p=0.121). Majority of patients received cefadroxil dose of 1000 mg BID (65%). No differences were observed in 30-day all-cause mortality (cefadroxil 5% vs other 1.6%, p=0.56), 30-day readmission (30% vs 15.9%, p=0.14), or 90-day recurrence (2.5% vs 14.29%, p=0.084). Similar outcomes were seen in sub-analyses comparing cefadroxil dose, MSSA vs Strep spp., and source risk of BSI (p=ns). Adverse effects from oral therapy were reported in 35% of cefadroxil vs 15% in other group (p=0.12); resulting in 0 patients in cefadroxil and 4 patients in the other group changing to alternative therapy. Conclusion Cefadroxil had similar clinical outcomes to other highly bioavailable antibiotic therapy for transitional therapy for MSSA and Streptococcal BSI. As cefadroxil can be dosed less frequently compared to certain other oral beta lactams, it may be an attractive option for outpatient therapy. Disclosures All Authors: No reported disclosures

Elevated left atrial stiffness index is a poor prognostic factor in heart failure with preserved ejection fraction undergoing transcatheter aortic valve replacement

Abstract Background Patients with severe aortic valve stenosis undergoing transcatheter aortic valve replacement (TAVR) present with a high prevalence of heart failure with preserved ejection fraction (HFpEF). An elevated left atrial stiffness index (LASI) has recently been recognized as a potential prognostic factor for worsened outcomes in HFpEF patients. Purpose This study investigates whether the LASI is a prognostic factor for outcomes following TAVR in HFpEF patients. Methods In this single-center retrospective study, patients with severe aortic valve stenosis who underwent TAVR at our center from February 2020 to May 2023 and had left ventricular ejection fraction >40% were included (Figure 1). The LASI was defined as the ratio of E/e’ to the left atrial reservoir strain from transthoracic echocardiography performed before and one week after TAVR. The primary endpoint was a composite outcome of all-cause mortality and cardiovascular events during the follow-up period. Results We analyzed 178 patients with a median age of 84 years, of whom 69% were female. During a median follow-up period of 549 days, 34 cases (19%) experienced the composite outcome. Multivariate Cox proportional hazards analysis using preoperative indices showed that LASI was independently associated with the occurrence of outcomes (HR 1.84 [95% CI; 1.15-2.95, P = 0.011] per 1.0 increase). A sub-analysis excluding cases had left bundle branch block postoperatively revealed a significant association between postoperative LASI and outcomes (HR 3.62 [95% CI; 2.01-6.51, P = <0.001] per 1.0 increase), particularly pronounced in patients with preoperative grade 2 left ventricular diastolic dysfunction (HR 4.38 [95%CI; 2.07-9.26, P=<0.001] per 1.0 increase) (Figure 2). Conclusion There is potential for LASI as a prognostic factor for outcomes following TAVR in HFpEF patients.

Proton pump inhibitors and all-cause mortality risk among cancer patients

BACKGROUND Proton pump inhibitors (PPIs) are widely used, including among cancer patients, to manage gastroesophageal reflux and other gastric acid-related disorders. Recent evidence suggests associations between long-term PPI use and higher risks for various adverse health outcomes, including greater mortality. AIM To investigate the association between PPI use and all-cause mortality among cancer patients by a comprehensive analysis after adjustment for various confounders and a robust methodological approach to minimize bias. METHODS This retrospective cohort study used data from the TriNetX research network, with electronic health records from multiple healthcare organizations. The study employed a new-user, active comparator design, which compared newly treated PPI users with non-users and newly treated histamine2 receptor antagonists (H2RA) users among adult cancer patients. Newly prescribed PPIs (esomeprazole, lansoprazole, omeprazole, pantoprazole, or rabeprazole) users were compared to non-users or newly prescribed H2RAs (cimetidine, famotidine, nizatidine, or ranitidine) users. The primary outcome was all-cause mortality. Each patient in the main group was matched to a patient in the control group using 1:1 propensity score matching to reduce confounding effects. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence interval (CI). RESULTS During the follow-up period (median 5.4 ± 1.8 years for PPI users and 6.5 ± 1.0 years for non-users), PPI users demonstrated a higher all-cause mortality rate than non-users after 1 year, 2 years, and at the end of follow up (HRs: 2.34-2.72). Compared with H2RA users, PPI users demonstrated a higher rate of all-cause mortality HR: 1.51 (95%CI: 1.41-1.69). Similar results were observed across sensitivity analyses by excluding deaths from the first 9 months and 1-year post-exposure, confirming the robustness of these findings. In a sensitivity analysis, we analyzed all-cause mortality outcomes between former PPI users and individuals who have never used PPIs, providing insights into the long-term effects of past PPI use. In addition, at 1-year follow-up, the analysis revealed a significant difference in mortality rates between former PPI users and non-users (HR: 1.84; 95%CI: 1.82-1.96). CONCLUSION PPI use among cancer patients was associated with a higher risk of all-cause mortality compared to non-users or H2RA users. These findings emphasize the need for cautious use of PPIs in cancer patients and suggest that alternative treatments should be considered when clinically feasible. However, further studies are needed to corroborate our findings, given the significant adverse outcomes in cancer patients.

Kidney and Cardiovascular Outcomes Among Patients With CKD Receiving GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis of Randomized Trials.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve cardiac and kidney outcomes in patients with diabetes; however their efficacy in individuals with reduced estimated glomerular filtration rate (eGFR) is uncertain. This study evaluated the effects of GLP-1RAs on kidney and cardiovascular (CV) outcomes in patients with chronic kidney disease (CKD). Systematic review and meta-analysis of randomized controlled trials (RCTs) reported through May 25, 2024. Adult participants in RCTs with baseline eGFR <60 mL/min/1.73 m2. RCTs including adults (≥18 years old) with varying degrees of kidney function, including individuals with CKD characterized by a baseline eGFR of less than 60 mL/min/1.73 m2, that compared GLP-1RAs with control treatments with respect to a composite kidney outcome, all-cause mortality, or a composite CV disease outcome. From among 212 screened studies, 12 trials involving that included participants with baseline eGFR <60 mL/min/1.73 m2 were included. Two independent investigators extracted the data. Pooled odds ratios (ORs) for composite kidney outcome, all-cause mortality, and composite CV outcome were estimated using random-effects models. Evidence certainty was assessed using the GRADE system. 17,996 RCT participants with baseline eGFR <60 mL/min/1.73 m2 were included in analyses. GLP-1RAs were significantly associated with a reduced risk of the composite kidney outcome (OR: 0.85 [95% CI 0.77-0.94]; p=0.001) with low heterogeneity (I2<0.01%). GLP-1RAs were also associated with a reduced the risk of a >30% eGFR decline (OR: 0.78, p=0.004), a >40% decline (OR: 0.76, p=0.01), and a >50% decline (OR: 0.72, p<0.001). Risk of all-cause mortality was also lower in the GLP-1RA group (OR: 0.77 [95% CI 0.60-0.98]; p=0.03), though there was high heterogeneity (I2=71.6%). Composite CV outcomes were also lower with the use of GLP-1R (OR: 0.86 [95% CI 0.74-0.99]; p=0.03; I2=40.3%). Sensitivity analyses restricted to human GLP-1 backbone agents showed enhanced benefits. Inconsistent kidney outcome definitions, focus on diabetic populations in most studies, and potential publication bias. GLP-1RAs improved kidney and cardiovascular outcomes, and survival in patients with CKD enrolled in an array of clinical trials.

Comparative performance of risk prediction indices for mortality or readmission following heart failure hospitalization.

Risk prediction indices used in worsening heart failure (HF) vary in complexity, performance, and the type of datasets in which they were validated. We compared the performance of seven risk prediction indices in a contemporary cohort of patients hospitalized for HF. We assessedthe performance ofthe Length of stay and number of Emergency department visits in the prior 6 months (LE), Length of stay, number of Emergency department visits in the prior 6 months, and admission N-Terminal prohormone of brain natriuretic peptide (NT-proBNP (LENT), Length of stay, Acuity, Charlson co-morbidity index, and number of Emergency department visits in the prior 6 months (LACE), Get With The Guidelines Heart Failure (GWTG), Readmission Risk Score (RRS), Enhanced Feedback for Effective Cardiac Treatment model (EFFECT), and Acute Decompensated Heart Failure National Registry (ADHERE)risk indices among consecutive patients hospitalized for HF and discharged alive from January 2017 to December 2019 in a network of hospitals in England. The primary composite outcome was 30-day all-cause mortality or readmission. We assessed model discrimination and overall accuracy using the C-statistic (higher values, better) and Brier score (lower values, better), respectively. Among 1206 patients in the cohort, 45.0% were female, mean (SD) age was 76.6 (11.7) years, and mean (SD) left ventricular ejection fraction was 43.0% (11.6). At 30days, 236 (19.6%) patients were readmitted and 28 (2.3%) patients died, with 264 (21.9%) patients experiencing either readmission or death. The LENT index offered the combination of greatest risk discrimination and accuracy for the primary composite outcome (C-statistic: 0.97; 95% CI 0.96, 0.98; 0.29; Brier score: 0.05). The LE (C-statistic: 0.95; 95% CI 0.93, 0.96; Brier score: 0.06) and LACE (C-statistic: 0.90; 95% CI 0.88, 0.92; Brier score 0.09) indices had high discrimination and accuracy. Discrimination and accuracy were modest with the RRS (C-statistic: 0.65; 95% CI 0.61, 0.69; Brier score: 0.16) and EFFECT (C-statistic: 0.64; 95% CI 0.60, 0.67; Brier score: 0.16) score; and poor with the GWTG-HF (C-statistic: 0.62; 95% CI 0.58, 0.66; Brier score: 0.17) and ADHERE (C-statistic: 0.54; 95% CI 0.50, 0.57; Brier score: 0.17) scores. In a study that compared the performance of seven risk prediction indices in a contemporary cohort of patients hospitalized for HF, the simple LENT index offered the greatest combination of discrimination and accuracy for the primary composite outcome of 30-day all-cause mortality or readmission. This three-variable index -using length of hospital stay, preceding emergency department visits and admission NT-proBNP level- is a practical and reliable way to assess prognosis following hospitalization for HF.

Impact of geriatric nutritional risk index on clinical outcomes in acute coronary syndrome patients: a comprehensive meta-analysis.

The Geriatric Nutritional Risk Index (GNRI), derived from serum albumin levels and body weight relative to ideal body weight, is a novel tool for assessing nutritional status. This meta-analysis explored the association between GNRI and the clinical outcomes in patients with acute coronary syndrome (ACS). We systematically searched PubMed, Embase, and Web of Science for studies evaluating the GNRI in patients with ACS. Inclusion criteria were observational studies reporting all-cause mortality or major adverse cardiovascular events (MACEs) among ACS patients categorized by low versus normal GNRI. Data extraction and quality assessment were independently performed by two authors, utilizing a random-effects model to account for potential heterogeneity. Eleven cohort studies, encompassing 18 616 patients with ACS, were included. A low GNRI was associated with significantly increased risks of all-cause mortality (RR, 1.95; 95% CI, 1.63-2.34; P < 0.001; I² = 32%) and MACEs (RR, 1.93; 95% CI, 1.62-2.29; P < 0.001; I² = 25%). Subgroup analyses for the all-cause mortality outcome showed consistent findings across varied study designs, patient demographics, and follow-up periods (P for subgroup differences all >0.05). Sensitivity analyses conducted by sequentially excluding individual studies confirmed the stability of these results. A low GNRI at the time of admission is a significant predictor of increased all-cause mortality and MACEs in patients with ACS.

Longitudinal Outcomes of Patients with Aortic Stenosis Stratified by Sex: An Asian Perspective.

Severe aortic stenosis (AS) stratified by sex has been increasingly studied in the European population. Sex-specific outcomes in Asian patients with AS remain poorly defined. Hence, we aimed to study the clinical characteristics and impact of sex in moderate-to-severe AS, undergoing both invasive and conservative interventions in an Asian cohort over 10 years. Consecutive data with echocardiographic diagnoses of AS were stratified according to gender in a tertiary academic center between 2011 and 2021. Demographics, comorbidities, and clinical outcomes were compared. Seven hundred and three (703) patients were included (56%, n = 397 were female). Calcific AS was the dominant etiology in both genders. Females had higher incidences of anemia (p < 0.001) and chronic kidney disease (p = 0.026); although, females had lower incidences of cardiovascular complications of coronary artery disease (CAD) (p = 0.002) and prior acute myocardial infarction (AMI) (p = 0.015). Echocardiographically, females had a smaller left ventricular outflow tract diameter (LVOTd) (p < 0.001), LV mass (p < 0.001), and left ventricle end diastolic volume (LVEDV) (p < 0.001). Conversely, the left atrial (LA) area (p < 0.001) and volume index (LAVI) (p < 0.001) were larger in females. Females had higher average E/e' (p = 0.010) ratios compared to males. The mean follow-up duration between genders was 4.1 ± 3.3 years. Upon univariate analysis, a greater proportion of female AS patients encountered cardiovascular (CV) hospitalization during follow-up (female: 27.5%, n = 109 vs. male: 18.3%, n = 56; p = 0.005) compared to male patients, but there were no significant differences for the outcomes of heart failure (p = 0.612), stroke (p = 0.664), and all-cause mortality (p = 0.827). Fewer females underwent aortic valve (AV) intervention compared to males (21.2% vs. 27.8%, p = 0.042), albeit with a longer duration to AV intervention (3.6 years ± 2.4 vs. 2.6 years ± 2.3, p = 0.016). In the severe AS cohort, female sex remained an independent predictor for subsequent heart failure (aHR 2.89, 95% CI 1.01-8.29, p = 0.048) and CV hospitalization (aHR 20.0, 95% CI 1.19-335, p = 0.037) after adjustments for age, ethnicity, body mass index (BMI), comorbidities, left ventricular ejection fraction (LVEF), and AV intervention. There was no difference in heart failure, stroke, and all-cause mortality outcomes between male and female Asian patients with moderate-to-severe AS. However, there were more cardiovascular hospitalizations, with fewer and longer duration to AV intervention in females compared to males in our cohort.

Cigar, Pipe, and Smokeless Tobacco Use and Cardiovascular Outcomes From Cross Cohort Collaboration

Cardiovascular health outcomes associated with noncigarette tobacco products (cigar, pipe, and smokeless tobacco) remain unclear, yet such data are required for evidence-based regulation. To investigate the association of noncigarette tobacco products with cardiovascular health outcomes. This cohort study was conducted within the Cross Cohort Collaboration Tobacco Working Group by harmonizing tobacco-related data and conducting a pooled analysis from 15 US-based prospective cohorts with data on the use of at least 1 noncigarette tobacco product ranging between 1948 and 2015. The analysis for this study was conducted between September 2023 and February 2024. The median (IQR) follow-up time for the all-cause mortality outcome was 13.8 (10.2-19.2) years. Current, sole, and exclusive use of noncigarette tobacco products. Sole use refers to using a noncigarette tobacco product without currently smoking cigarettes. Exclusive use means using only the noncigarette tobacco product and never having smoked cigarettes. Myocardial infarction, stroke, heart failure, atrial fibrillation, total coronary heart disease, total cardiovascular disease (CVD), coronary heart disease mortality, CVD mortality, and all-cause mortality. Of 103 642 participants (mean [SD] age, 55.7 [13.2] years; 49 550 female [47.8%] and 54 092 male [52.2%]), current use rates were 26 962 participants (26.3%) for cigarettes, 1147 participants (2.1%) for cigars, 530 participants (1.2%) for pipes, and 1410 participants (2.1%) for smokeless tobacco. Current cigar use was associated with stroke (hazard ratio [HR], 1.25; 95% CI, 1.01-1.55), atrial fibrillation (HR, 1.32; 95% CI, 1.13-1.53), and heart failure (HR, 1.29; 95% CI, 1.10-1.51) compared with never using cigars in the model adjusted for demographic and socioeconomic factors, cardiovascular risk factors, and cohort. Sole (HR, 1.34; 95% CI, 1.12-1.62) and exclusive (HR, 1.53; 95% CI, 1.20-1.96) cigar use was associated with stroke compared with never using cigars or cigarettes. Current pipe use was associated with heart failure (HR, 1.23; 95% CI, 1.01-1.49) compared with never using pipes, and sole pipe use was associated with myocardial infarction (HR, 1.43; 95% CI, 1.17-1.74) compared with never using pipes or cigarettes. Current use of smokeless tobacco was associated with coronary heart disease mortality (HR, 1.31; 95% CI, 1.08-1.59) and myocardial infarction (HR, 1.20; 95% CI, 1.03-1.39) compared with never using smokeless tobacco. Sole and exclusive smokeless tobacco use demonstrated associations with total CVD (HR, 1.34; 95% CI, 1.19-1.50 and HR, 1.34; 955 CI, 1.13-1.59, respectively), total coronary heart disease (HR, 1.41; 95% CI, 1.21-1.64 and HR, 1.36; 95% CI, 1.08-1.70, respectively), heart failure (HR, 1.41; 95% CI, 1.22-1.64 and HR, 1.70; 95% CI, 1.40-2.06, respectively), and cardiovascular (HR, 1.41; 95% CI, 1.20-1.65 and HR, 1.54; 95% CI, 1.24-1.91, respectively) and all-cause (HR, 1.46; 95% CI, 1.34-1.60 and HR, 1.39; 95% CI, 1.22-1.58, respectively) mortality compared with never using smokeless tobacco or cigarettes. In this study, there were distinct risk patterns associated with the use of noncigarette tobacco products. These findings may carry implications for public health and regulation of noncigarette tobacco products.

Pregnancy Outcomes and All-Cause Mortality After Pregnancy Among US-Born Women With Perinatally Acquired HIV.

Maternal and pregnancy outcomes among women with perinatally acquired HIV (PHIV) versus women with HIV acquired through other routes (NPHIV) are not fully understood. US-born women during 2005-2015 in New York City. We used data from the New York City HIV surveillance registry, Expanded Perinatal Surveillance database, and Vital Statistics, to compare pregnancy and all-cause mortality outcomes among women with PHIV versus NPHIV delivering infants during 2005-2015. There were 186 deliveries among 137 women with PHIV and 1188 deliveries among 910 women with NPHIV. Women with PHIV were younger at delivery, more likely to be aware of their HIV status, and less likely to use substances or be incarcerated. At the time of delivery, women with PHIV were more likely to have HIV RNA >1000 copies/mL (34% vs. 19%), CD4 <200 cells/µL (18% vs. 7%; median CD4 300 cells/µL vs. 435 cells/µL), to have adequate prenatal care (43% vs. 35%), and to deliver by elective C-section (63% vs. 49%). There were no differences in intrapartum and neonatal antiretroviral therapy use, perinatal transmission, gestational age, and birth weight of the infants, nor infant mortality. Women with NPHIV had higher survival than women with PHIV (RR = 2.29, P = 0.004; age-adjusted risk ratio = 3.23, P < 0.001; age and CD4 adjusted risk ratio = 2.09, P = 0.046). Women with PHIV had lower long-term survival after delivery likely because of limited HIV treatment options in childhood and a longer duration of HIV infection, underscoring the importance of close follow-up and tailored support services beyond the postpartum period.

Prediction and Longer-Term Outcomes of All-cause and Cardiovascular Mortality in the HEART-FID Trial.

The HEART-FID trial is the largest trial to test intravenous iron (ferric carboxymaltose [FCM]) versus placebo in patients with heart failure and iron deficiency. The results showed a modest but non-statistically significant reduction in important clinical outcomes, including all-cause mortality. We sought to understand the factors associated with all-cause mortality. Data on patients enrolled in HEART-FID were used to determine factors associated with all-cause mortality via multivariable models. The models included key clinical characteristics, including treatment interactions identified in the primary analysis (age by sex and country of enrollment). All-cause mortality at 12 months and over the full duration of follow-up (median 23.1 months) was evaluated using Cox proportional hazard regression. A total of 3065 patients had 737 all-cause mortality events over the duration of the trial, with 289 events occurring in the first 12 months. Fewer patients randomized to FCM died by 12 months compared with the placebo group (131 receiving FCM vs. 158 receiving placebo; hazard ratio 0.82 [95% confidence interval: 0.65-1.04]). Patients who died were more likely to be older with diabetes, atrial fibrillation, lower ejection fraction and estimated glomerular filtration rate, and a higher N-terminal pro b-type natriuretic peptide (NT-proBNP) level. The 3 multivariable factors most strongly associated with all-cause mortality at 12 months were NT-proBNP level, country of enrollment, and 6-minute walk test distance. Similar results were seen for predicting all-cause mortality over the entire follow-up; the addition of an age × sex × FCM interaction yielded statistically significant results, with greater association of benefit from FCM found for older women than for other patient subgroups. FCM, compared with placebo, was associated with a potentially clinically meaningful (but not statistically significant) reduction in all-cause mortality, with key predictors of mortality being natriuretic peptide level, country of enrollment, and 6-minute walk test distance.

Arrhythmogenic Right Ventricular Cardiomyopathy: The Importance of Biventricular Strain in Risk-Stratification.

Despite arrhythmogenic right ventricular cardiomyopathy (ARVC) being predominantly a right ventricular (RV) disease, concomitant left ventricular (LV) involvement has been recognized. ARVC is diagnosed by the RV-centric 2010 Task Force Criteria(TFC) using routine echocardiography, but previous studies have suggested that strain imaging may be more sensitive to detect RV and LV dysfunction. No data however are available regarding the additional value of combining biventricular strain for risk stratification. This study aims to assess the prognostic value of both LV global longitudinal strain (GLS) and RV free wall strain (FWLS) in patients with ARVC. To accomplish this, 204 patients who met the TFC for the ARVC spectrum were included. Patients (age 41 ± 17 years,55% men) were divided into impaired(n = 33), discordant (RV or LV impaired, n = 70), and normal (n = 101) strain groups based on a value of ≥18% for both ventricles. During a follow-up of 87 [24-136] months, 57 (28%) experienced the composite outcome of all-cause mortality, arrhythmic events, implantable cardioverter defibrillator therapy and heart failure events, and a significant difference in event-free survival was observed (p <0.001) between the 3 groups. In the multivariable analysis, the strain groups remained associated with outcomes (p = 0.014) after adjusting for age, sex, history of syncope and definite ARVC diagnosis. A subanalysis including only definite and borderline diagnosed ARVC confirmed that the strain groups were independently predictive of the endpoint (p = 0.023). In conclusion, biventricular involvement by strain analysis may help risk stratification in ARVC patients, with the worst outcomes of patients with both RV and LV impaired strain.

Reevaluating Normal-Flow Low-Gradient Severe Aortic Stenosis: Clinical Phenotypes and Outcomes in Severe Aortic Stenosis Among TAVR Patients.

Aortic stenosis (AS) is a complex condition with various hemodynamic subtypes, each with distinct clinical profiles and outcomes. This study aimed to assess the characteristics and outcomes of different AS phenotypes based on flow and gradient patterns. In this retrospective cohort study, we included 930 patients who underwent transcatheter aortic valve replacement (TAVR) for severe symptomatic AS at Mayo Clinic sites from 2012-2017. Patients were classified into three groups: high gradient (HG), low-flow low-gradient (LFLG), and normal-flow low-gradient (NFLG). Baseline clinical, echocardiographic, and computed tomography (CT) characteristics, including aortic valve area (AVA), aortic valve calcium score (AVCS), left ventricular ejection fraction (LVEF), and the prevalence of tricuspid regurgitation (TR) and atrial fibrillation were analyzed. One- and five-year all-cause mortality outcomes were compared using Kaplan-Meier analysis and Cox proportional hazards models. The final cohort included 273 patients in the NFLG group (29.4%), 563 in the HG group (60.5%), and 94 in the LFLG group (10.1%). After reevaluation and careful review of the echocardiograms, 41 NFLG patients were reclassified into the LFLG group. LFLG patients had the highest prevalence of atrial fibrillation/flutter (60%) and TR (17%). AVCS was significantly lower in NFLG compared to HG and LFLG groups. One-year mortality was highest in the LFLG group (17.4%), followed by HG (13.9%) and NFLG (10.9%), but the difference was not statistically significant (p=0.2). Five-year mortality rate was higher in the LFLG group (55.6%) compared to NFLG (47.2%) and HG (47.9%) but did not reach statistical significance (p=0.2). LFLG AS is associated with more comorbidities and higher mortality compared to HG and NFLG groups, though differences in mortality were not statistically significant. The NFLG group, after close review and reclassification, showed the least significant AS. Randomized trials are needed to clarify the prognosis and management of NFLG AS.

Association between serum urate levels and all-cause mortality, cardiovascular and renal outcomes among gout patients in Singapore

ObjectivesWe investigated the longitudinal association between Serum Urate (SU) level and Acute Myocardial Infarction (AMI), Stroke, End Stage Renal Failure (ESRF) and all-cause mortality.DesignWe conducted a retrospective hospital-based cohort study of individuals with gout managed in specialist outpatient clinics. Cox proportional hazards regression was used to estimate HR and 95% CI, with adjustments for potential confounders. Where the proportional hazard assumption was violated, stratified Cox regression was applied instead.SettingAn acute care tertiary hospital in Singapore.ParticipantsIndividuals with a first gout diagnosis between 2007–2017, identified through (i) primary discharge diagnosis, (ii) diagnosis from the Rheumatology SOC (iii) patient history of a clinical encounter at the Rheumatology SOC plus use of urate-lowering therapy/colchicine.Main outcome measuresAll-cause mortality, AMI, Stroke and ESRF ascertained through data linkage with the National Registry of Diseases Office.ResultsThe final cohort comprised 2,866 individuals. Post follow-up, there were 800 deaths and 362, 218 and 191 occurrences of AMI, ESRF and stroke respectively. Compared to the reference (second-lowest) SU quartile, being in the highest SU quartile was associated with a significantly increased hazard for mortality (HR:1.66, 95% CI:1.36–2.03), incident ESRF (HR:3.02, 95% CI:2.00-4.56), and increased hazard for incident AMI (HR:1.42, 95% CI:1.06–1.91). The p-trend for all 3 outcomes was significant. No significant association was found between SU quartile and hazard for incident stroke.ConclusionsThis study found that individuals with gout managed at SOC who had higher baseline SU levels had an increased hazard for all-cause mortality, ESRF, and AMI.Clinical trial numberNot applicable.

A complex systems approach to mosaic loss of the Y chromosome.

Mosaic loss of Y chromosome (mLOY) is an acquired condition wherein a sizeable proportion of an organ's cells have lost their Y. Large-scale cohort studies have shown that mLOY is age-dependent and a strong risk factor for all-cause mortality and adverse outcomes of age-related diseases. Emerging multi-omics approaches that combine gene expression, epigenetic and mutational profiling of human LOY cell populations at single-cell levels, and contemporary work in in vitro cell and preclinical mouse models have provided important clues into how mLOY mechanistically contributes to disease onset and progression. Despite these advances, what has been missing is a system-level insight into mLOY. By integrating the most recent advances in wide-ranging aspects of mLOY research, we summarize a unified model to understanding the cause and consequence of mLOY at the molecular, cellular, and organismal levels. This model, referred to as the "Unstable Y Cascade model," states that (i) the rise and expansion of LOY result from interaction by the inherently unstable Y, germline genetic and epigenetic variants, and numerous cell-intrinsic and external factors; (ii) LOY initiates genomic, epigenomic, and transcriptomic alterations in X and autosomes, thereafter induces a cascade of tissue-specific cellular alterations that contribute locally to the onset and progression of diseases; and (iii) LOY cells exert paracrine effects to non-LOY cells, thereby amplifying LOY-associated pathological signaling cascades to remote non-LOY cells. This new model has implications in the development of therapeutic interventions that could prevent or delay age-related diseases via mitigating mLOY burden.

All-Cause and Cause-Specific Mortality in Tourette Syndrome and Chronic Tic Disorder.

Tourette syndrome (TS) and chronic tic disorder (CTD) may be associated with an increased risk of mortality, but specific causes of death are poorly understood. In this matched cohort and sibling cohort study, we estimated the risk of all-cause and cause-specific mortality in individuals with TS/CTD, compared with unaffected matched individuals and unaffected full siblings. We identified all individuals diagnosed with TS/CTD in the Swedish National Patient Register who were living in the country between 1973 and 2020 and matched them (1:10) to individuals without TS/CTD from the general population. We also identified their siblings without TS/CTD. All-cause and cause-specific mortality outcomes, based on the International Classification of Diseases codes, were extracted from the Cause of Death Register. Covariates included sociodemographic variables and psychiatric disorders. Risks of mortality were estimated using Cox proportional hazards regression models. We included 10,280 individuals with TS/CTD and 102,800 matched individuals without TS/CTD. In adjusted models, individuals with TS/CTD had an 86% increased hazard of all-cause mortality (hazard ratio: 1.86, 95% confidence interval: 1.65-2.11). The increased risk was observed for both natural (particularly nervous, digestive, and respiratory system diseases) and unnatural causes of death (including suicides and accidents). The sibling comparison showed similar results, indicating that the associations were unlikely to be explained by familial confounding. Individuals with TS/CTD are at increased risk of death due to both natural and unnatural causes. As some of these deaths are potentially preventable, greater focus on the somatic health of individuals with TS/CTD is warranted. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The potential of precision diabetology for type 2 diabetes treatment-evidence from a meta-regression for all-cause mortality from large cardiovascular outcome trials.

Two prerequisites must be met for the precision treatment approach to be beneficial for treated individuals. First, there must be treatment heterogeneity; second, in case of treatment heterogeneity, clinical predictors to identify people who would benefit from one treatment more than from others must be available. There is an established meta-regression approach to assess these two prerequisites that relies on measuring the variability of a clinical outcome after treatment in placebo-controlled randomised trials. We recently applied this approach to the treatment of type 2 diabetes for the clinical outcomes of glycaemic control and body weight and repeat it for the clinical outcome of all-cause mortality. We performed a meta-regression analysis using digitalized individual participant information on time to death from 10 large cardiovascular outcome trials (7563 deaths from 99,746 participants) on DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT-2 inhibitors with respect to the variability of all-cause mortality and its potential predictors after treatment. The adjusted difference in log(SD) values of time to death between the verum and placebo arms was -0.036 (95%-CI: -0.059; -0.013), showing larger variability of time to death in the placebo arms. No clinical predictors were found to explain treatment heterogeneity. This analysis suggests that the potential of the precision treatment approach in type 2 diabetes is low, at least with regard to improvement of all-cause mortality in population with high cardiovascular risk. This extends our previous findings for the clinical outcomes of glycaemic control and body weight.

Turbulence in the system: Higher rates of left-without-being-seen emergency department visits and associations with increased risks of adverse patient outcomes since 2020.

To examine risks of severe adverse patient outcomes shortly after a left-without-being-seen emergency department (LWBS ED) visit since 2020. In this retrospective study using linked administrative data, we examined temporal trends in monthly rates of ED and LWBS visits for adults in Ontario, Canada, 2014‒2023. In patient-level analyses restricted to the first eligible LWBS ED visit, we used modified Poisson regression to compare the composite outcome of 7-day all-cause mortality or hospitalization following a LWBS ED visit for April 1, 2022‒March 31, 2023 (recent period) to April 1, 2014‒March 31, 2020 (baseline period), adjusted for age, sex, and Charlson comorbidity index. Despite fewer monthly ED visits since 2020, temporal trends revealed sustained increases in monthly LWBS rates. LWBS ED visits after April 1, 2020 exceeded the baseline period's single-month LWBS maximum of 4.0% in 15 out of 36 months. The composite outcome of 7-day all-cause mortality or hospitalization was 3.4% in the recent period versus 2.9% in the baseline period (adjusted risk ratio [aRR] 1.14, 95% confidence interval [CI] 1.11‒1.18) and remained elevated at 30 days (6.2% vs. 5.8%, respectively; aRR 1.05, 95% CI 1.03‒1.07), despite similar rates of post-ED outpatient visits (7-day recent and baseline: 38.9% and 39.7%, respectively, p=0.38; 30-day: 59.4% and 59.7%, respectively, p=0.05). The rate of short-term mortality or hospitalization after a LWBS ED visit has recently increased, despite fewer ED visits/month and similar proportion of post-ED outpatient encounters. This concerning signal should prompt interventions to address system- and population-level causes.