Baseline Mortality Risk Research Articles

Left Atrial Appendage Closure With Catheter Ablation vs. Ablation Alone on Outcomes of Atrial Fibrillation in Heart Failure With Reduced Ejection Fraction: A Propensity Score-Matched Analysis.

Background Combining left atrial appendage closure with catheter ablation (LAACCA) has been proposed as a potential approach to improving outcomes by simultaneously addressing arrhythmia and reducing stroke risk. This study comparesthe in-hospital outcomes of LAACCA vs. catheter ablation (CA) alone for atrial fibrillation (AFib) in patients with heart failure with reduced ejection fraction (HFrEF). Methods We analyzed adult hospitalizations with HFrEF and AFib who underwent LAACCA or CA alone from the 2016-2020 nationwide inpatient sample using validated ICD-10 codes. Propensity score matching, accounting for patient-, hospital-, and procedure-level covariates, illness severity, and baseline risk of mortality, was used to alleviate bias in nonrandomized treatment assignments. The primary endpoints included all-cause in-hospital mortality, hospital stay, and hospitalization costs. Secondary endpoints included postprocedural complication rates. Prolonged hospitalization was defined as hospital stay in the top decile of hospital stay in each cohort. All statistical analyses in the study were based on weighted hospital data. Results About 233,865 HFrEF patients were hospitalized for AFib. Approximately 27,945 (11.9%) underwent LAACCA, while 205,920 (88.1%) underwent CA only. The cohort comprised mostly males (151,077; 64.6%) (mean age: 67.4; SD: 4.3). The propensity score-matched cohort comprised 18,195 LAACCAs and 18,195 CAs; all covariate imbalances were alleviated. LAACCA was associated with a higher rate of prolonged hospital stay (7.6 vs 5.6 days; P<0.001), a higher mortality rate (209 (1.1%) vs. 160 (0.9%); P=0.011), and higher mean hospital costs ($289,960 vs. $183,932; P<0.001) compared with CA alone. LAACCA was associated with a higher incidence of acute myocardial ischemia (528 (2.9%) vs. 455 (2.5%); P=0.013), complete atrioventricular block (1,200 (6.6%) vs. 892 (4.9%); P=0.004), need for implantable device therapy (1,510 (8.3%) vs. 1,348 (7.4%); P=0.017), pneumothorax (328 (1.8%) vs. 91 (0.5%); P<0.0001), hemothorax (200 (1.1%) vs. 127 (0.7%); P<0.0001), pneumonia (983 (5.4%) vs. 546 (3.0%); P<0.0001), vascular access complications (346 (1.9%) vs. 255 (1.4%); P=0.046), and septicemia (309 (1.7%) vs. 182 (1.0%); P<0.001). CA was associated with a greater incidence of cardiac tamponade (237 (1.3%) vs. 382 (2.1%); P=0.010)and femoral artery pseudoaneurysm (364 (0.2%) vs. 91 (0.5%); P<0.001). Conclusion LAACCA was correlated with highermortality odds compared to CA alone for atrial fibrillation in HFrEF.

Sex and Racial Disparities in Hospitalization and Outcomes of Multiple Myeloma with ESRD

Background/Objectives: Renal failure severe enough to require dialysis (ESRD) complicates multiple myeloma (MM) in up to 10% of hospitalizations. This study examined disparities in hospitalization and outcomes among MM and ESRD patients according to sex and race Methods: From the nationwide inpatient sample database, we analyzed 4,615 adult hospitalizations for patients with MM and ESRD between January 1, 2016, and December 31, 2020. Baseline sex and race characteristics were analyzed using chi-square tests and Student's t-test. Hierarchical multivariable logistic regression analysis evaluated the odds of primary and secondary outcomes. All patient refined-diagnosis-related groups (APR-DRG) metrics and the Charlson comorbidity index (CCI) metrics were used to adjust illness severity, baseline risk of mortality, and comorbidity burden. Prolonged hospitalization was defined as the length of hospital stay in the top decile (23 days). Results: Women with MM and ESRD were significantly older (65.5 vs. 58.1 years; P = 0.045) and had a higher prevalence of COPD (17.5 vs. 12.1%; P = 0.022), lymphopenia (14.1% vs. 6.9%; P 0.001), osteoporosis (4% vs. 0.5%; P 0.001), and electrolyte abnormalities (1.7% vs. 0.4; P = 0.014), whereas men had higher prevalence of tobacco use (35.2% vs. 22.6%; P &amp;lt; 0.001), coronary artery disease (163.5% vs. 10.2%; P = 0.008), and previous PCI (4.6% vs. 1.4%; P = 0.010). Compared with nonwhite patients, White Americans were older (67.3 vs. 63.6; P &amp;lt; 0.001) and had a higher prevalence of obesity (6.7% vs. 3.8%; P = 0.047), diabetes (37.3% vs. 24.3%; P &amp;lt; 0.001), and electrolyte abnormalities (2.3% vs. 1%; P = 0.032). A higher prevalence of COPD (17.6% vs. 11%; P = 0.004) was observed in nonwhite patients. Compared with female sex, male sex was significantly correlated with greater odds of mortality (11.6% vs. 9.7%; aOR: 1.32; 95% CI: 1.03-2.08; P = 0.030), bone marrow transplantation (25.0% vs. 22.3%; aOR: 1.15; 95% CI: 1.03-1.58; P = 0.037), and any MACE (3.9% vs. 2.1%; aOR: 3.9; 95% CI: 1.12-1.0; 1.06-2.29; P=0.028). Female sex was correlated with greater odds of VTE (11.3% vs. 7.6%; aOR: 1.59; 95% CI: 1.17-2.61; P = 0.039), depression (1.4% vs. 0.5%; aOR: 1.08; 95% CI: 1.04-1.22; P = 0.028), and prolonged hospitalization (15.5% vs. 13.1%; aOR: 1.24; 95% CI: 1.14-2.66; P = 0.027). White race was correlated with a greater likelihood of ASCT (10.6%; aOR: 1.15; 95% CI: 1.08-1.93; P = 0.026) and depression (1.4%; aOR: 1.08; 95% CI: 1.04-1.32; P = 0.028). Black race was correlated with greater odds of VTE (12.1%; aOR: 1.35; 95% CI: 1.24-1.93; P = 0.048) and any MACE (2.8%; aOR: 1.32; 95% CI: 1.07-3.27; P = 0.035) and lower odds of ASCT (5.4%; aOR: 0.45; 95% CI: 0.27-0.76; P = 0.003). Hispanic and Asian/Pacific Islander descent were associated with significantly higher mortality (12.1%, P = 0.015 and 12.2%, P = 0.002, respectively) and greater likelihood of major transfusion (36.4%, P = 0.029 and 30.3%, P = 0.049, respectively). Asian/Pacific Islander descent was also correlated with greater odds of ARF (39.4%; aOR: 1.61; 95% CI: 1.34-2.46; P = 0.016). Native American descent was correlated with a greater risk of VTE (8.9%; aOR: 4.14; 95% CI: 0.90-8.97; P = 0.068). No significant differences in mean hospital stay and hospital cost were observed by race and sex among patients with MM and ESRD. Conclusion: Male patients exhibited higher odds of mortality, bone marrow transplantation, and major adverse cardiovascular events, whereas female patients exhibited greater odds of venous thromboembolism, depression, and prolonged hospital stays. Racial disparities were also evident; white patients were more likely to receive autologous stem cell transplantation and report depression, whereas nonwhite patients, especially those of Black, Hispanic, Asian/Pacific Islander descent, had higher risk of venous thromboembolism, major adverse cardiovascular events, and mortality.

12620 Developing Hospital Protocols For Managing Patients With Hypertriglyceridemia-induced Acute Pancreatitis In Diabetic Ketoacidosis Hospitalizations

Abstract Disclosure: U. Agbedia-ejughemre: None. Methods: We queried the combined 2017-2020 nationwide inpatient sample database for all adult hospitalizations for DKA with and without HTG-AP using the ICD-10 revision codes. Baseline characteristics were compared between DKA hospitalizations with and without HTG-AP using Pearson’s χ2 tests and Student’s t-test for categorical and continuous variables. Study endpoints were the incidence, predictors, and outcomes of HTG-AP, including mortality, hospitalization duration, mean hospital costs, and acute in-hospital complications (sepsis, ARDS, and acute renal failure). Predictors of HTG-AP were assessed using stepwise multivariable logistic regression analysis. Illness severity, baseline risk of mortality, and comorbidity burden were adjusted using APR-DRG metrics and CCI. Prolonged hospitalization was defined as the length of hospital stay in the top decile of hospital stay for all hospitalizations in the study. Results: We analyzed 630,435 hospitalizations for DKA. The study cohort was 51.4% male, 57.6% white Americans and 26.1% Blacks, with a mean age of 40 (SD, 16.2) years. Incidence of HTG-AP was 2.1% (13,445). Hospitalizations with HTG-AP were older (mean age: 44 vs. 40 years; P&amp;lt;0.001) and had greater comorbidity (CCI score of 2: 38.7 vs. 33.8; P&amp;lt;0.001) compared with DKA hospitalizations without HTG-AP. While DKA hospitalizations showed an uptrend, increasing from 105,769 to 199,429 hospitalizations (Average annual percent change [AAPC]: 27.04%; P=0.029), the incidence of HTG-AP showed a downtrend from 2650 (2.5%) to 4085 (2.0%) (P=0.006). Predictors of HTG-AP included Hispanic (aOR: 2.45; 95% CI: 1.95-3.07; P&amp;lt;0.001) or Asian race (aOR: 2.48; 95% CI: 1.37-4.48; P=0.003), private insurance (aOR: 1.57; 95% CI: 1.10-2.25; P=0.013), self-pay (aOR: 2.2; 95% CI: 1.49-3.27; P&amp;lt;0.001), APR-DRG moderate risk of mortality (aOR: 1.52; 1.21-1.92; P&amp;lt;0.001), APR-DRG major loss of function (aOR: 1.46; 95% CI: 1.31-1.69; P&amp;lt;0.001), dyslipidemia (aOR: 1.87; 95% CI: 1.47-2.38; P&amp;lt;0.001), hypertension (aOR: 1.39; 95% CI: 1.13-1.72; P=0.002), obesity (aOR: 3.09; 95% CI: 2.42-3.96; P&amp;lt;0.001), obstructive sleep apnea (aOR: 2.05; 95% CI: 1.35-3.10; P=0.001), chronic liver disease (aOR: 9.44; 95% CI: 6.61-13.48; P&amp;lt;0.001), old MI (aOR: 2.11; 95% CI: 1.02-4.38; P=0.045), and COPD (aOR: 2.31; 95% CI: 1.47-3.64; P&amp;lt;0.001). DKA hospitalizations with HTG-AP were correlated with higher risk of septicemia (aOR: 1.20; 95% CI: 1.05-1.69; P=0.029), ARDS (aOR: 1.24; 95% CI; 1.04-2.07; P=0.004), and resource use, including prolonged hospitalization (26.3% vs. 11.1%; P&amp;lt;0.001), and higher mean hospital costs ($57,773 vs. $32,692; P&amp;lt;0.001). Conclusion: HTG-AP was linked to worse outcomes, excluding mortality, in hospital admissions for DKA. There is a need for enhanced diagnostic guidelines and protocols targeting this subgroup of patients could improve outcomes. Presentation: 6/2/2024

Baseline weight recovery and mortality risk in head and neck cancer.

As a surrogate of malnutrition, degree of weight loss and recovery from head and neck cancer (HNC) treatment is understudied. The influence of modifiable factors that affect weight, including speech/language pathology (SLP) and nutrition counseling, is also poorly defined. We characterize weight loss trends, baseline weight recovery (BWR), and the impact of interdisciplinary care on oncologic outcomes. Retrospective cohort study assessing 266 newly diagnosed patients with HNC who completed curative-intent radiation (definitive or adjuvant) between January 2016 to January 2022. Relevant treatment factors were analyzed using multivariable Cox regression models. Altogether, 266 patients completed full-course radiation therapy (RT), encompassing definitive chemoRT (53.0%), surgery with chemoRT (18.4%), surgery with RT (17.7%), and RT alone (10.9%). Patient weight reached a nadir at median 3.0 months (IQR 3.0-11.3) after radiation, with a median weight loss of 12.6% (IQR 7.9-18.7). Notably, only 47.4% exhibited BWR. For those who recovered, median time to BWR was 10.5 months (IQR 3.0-24.0). On multivariable analysis, BWR by 6 months was significantly associated with overall survival (HR 0.28 [95% CI 0.10-0.76], p = 0.013), as was SLP consultation (HR 0.40 [95% CI 0.17-0.92], p = 0.031) and nutrition consultation (HR 0.34 [95% CI 0.13-0.89], p = 0.028). A high proportion of patients with HNC fail to recover baseline weight after treatment; those that do can take longer than expected to return. Failure to recover baseline weight is associated with a notable decrease in survival. Similarly, SLP and nutrition consultation are independent, modifiable determinants correlated with outcomes, supporting the emphasis on multidisciplinary management. Measures to promote BWR may reduce mortality.

Survival outcomes after breast cancer surgery among older women with early invasive breast cancer in England: population-based cohort study.

This study assessed the influence of age, co-morbidity and frailty on 5-year survival outcomes after breast conservation surgery (BCS) with radiotherapy (RT) versus mastectomy (with or without RT) in women with early invasive breast cancer. Women aged over 50 years with early invasive breast cancer diagnosed in England (2014-2019) who had breast surgery were identified from Cancer Registry data. Survival estimates were calculated from a flexible parametric survival model. A competing risk approach was used for breast cancer-specific survival (BCSS). Standardized survival probabilities and cumulative incidence functions for breast cancer death were calculated for each treatment by age. Among 101 654 women, 72.2% received BCS + RT and 27.8% received mastectomy. Age, co-morbidity and frailty were associated with overall survival (OS), but only age and co-morbidity were associated with BCSS. Survival probabilities for OS were greater for BCS + RT (90.3%) versus mastectomy (87.0%), and the difference between treatments varied by age (50 years: 1.9% versus 80 years: 6.5%). Cumulative incidence functions for breast cancer death were higher after mastectomy (5.1%) versus BCS + RT (3.9%), but there was little change in the difference by age (50 years: 0.9% versus 80 years: 1.2%). The results highlight the change in baseline mortality risk by age for OS compared to the stable baseline for BCSS. For OS, the difference in survival probabilities for BCS + RT and mastectomy increased slightly with age. The difference in cumulative incidence functions for breast cancer death by surgery type was small regardless of age. Evidence on real-world survival outcomes among older populations with breast cancer is informative for treatment decision-making.

Influence of incomplete death information on cumulative risk estimates in US claims data.

Administrative claims databases often do not capture date or fact of death, so studies using these data may inappropriately treat death as a censoring event-equivalent to other withdrawal reasons-rather than a competing event. We examined 1-, 3-, and 5-year inverse-probability-of-treatment weighted cumulative risks of a composite cardiovascular outcome among 34 527 initiators of telmisartan (exposure) and ramipril (referent), who were aged ≥55 years, in Optum (United States) claims data from 2003 to 2020. Differences in cumulative risks of the cardiovascular endpoint due to censoring of death (cause-specific), as compared with treating death as a competing event (subdistribution), increased with greater follow-up time and older age, where event and mortality risks were higher. Among ramipril users, 5-year cause-specific and subdistribution cumulative risk estimates per 100, respectively, were 16.4 (95% CI, 15.3-17.5) and 16.2 (95% CI, 15.1-17.3) among ages 55-64 (difference= 0.2) and were 43.2 (95% CI, 41.3-45.2) and 39.7 (95% CI, 37.9-41.4) among ages ≥75 (difference= 3.6). Plasmode simulation results demonstrated the differences in cause-specific versus subdistribution cumulative risks to increase with increasing mortality rate. We suggest researchers consider the cohort's baseline mortality risk when deciding whether real-world data with incomplete death information can be used without concern. This article is part of a Special Collection on Pharmacoepidemiology.

Association of Periodic Limb Movements and Obstructive Sleep Apnea With Risk of Cardiovascular Disease and Mortality.

Obstructive sleep apnea is a well-established risk factor for cardiovascular disease (CVD). Recent studies have also linked periodic limb movements during sleep to CVD. We aimed to determine whether periodic limb movements during sleep and obstructive sleep apnea are independent or synergistic factors for CVD events or death. We examined data from 1049 US veterans with an apnea-hypopnea index (AHI) <30 events/hour. The primary outcome was incident CVD or death. Cox proportional hazards regression assessed the relationships between the AHI, periodic limb movement index (PLMI), and the AHI×PLMI interaction with the primary outcome. We then examined whether AHI and PLMI were associated with primary outcome after adjustment for age, sex, race and ethnicity, obesity, baseline risk of mortality, and Charlson Comorbidity Index. During a median follow-up of 5.1 years, 237 of 1049 participants developed incident CVD or died. Unadjusted analyses showed an increased risk of the primary outcome with every 10-event/hour increase in PLMI (hazard ratio [HR], 1.08 [95% CI, 1.05-1.13]) and AHI (HR, 1.17 [95% CI, 1.01- 1.37]). Assessment associations of AHI and PLMI and their interaction with the primary outcome revealed no significant interaction between PLMI and AHI. In fully adjusted analyses, PLMI, but not AHI, was associated with an increased risk of primary outcome: HR of 1.05 (95% CI, 1.00-1.09) per every 10 events/hour. Results were similar after adjusting with Framingham risk score. Our study revealed periodic limb movements during sleep as a risk factor for incident CVD or death among those who had AHI <30 events/hour, without synergistic association between periodic limb movements during sleep and obstructive sleep apnea.

Validation of the GRACE 3.0 score and redefinition of the risk threshold for early invasive treatment in non-ST-segment elevation acute coronary syndromes: a modelling study from five countries

Abstract Background Clinical use of the GRACE scoring system is recommended across international guidelines to guide early treatment stratification in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). Recently, the machine learning-based GRACE 3.0 score was derived from patients with NSTE-ACS undergoing contemporary treatment approaches. External validation studies and the reassessment of clinical risk categories are lacking. Purpose We aimed to evaluate the predictive performance of the GRACE 3.0 score and to explore clinically meaningful risk groups in contemporary patients with NSTE-ACS. Methods We studied the GRACE 3.0 score in 8070 patients with NSTE-ACS in contemporary ACS cohorts from Denmark (VERDICT, n=2147), Germany (Heidelberg-ACS, n=2034), Italy and Spain (CORALYS, n=1650), and Switzerland (SPUM-ACS, n=2239). Heterogeneity in the treatment effect of very early invasive management (within 12 hours) or standard invasive management (within 48 to 72 hours) on the primary composite outcome of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure in relation to baseline mortality risk was assessed in 2147 patients enrolled in the VERDICT trial who were randomized to different timing of invasive treatment. Results The GRACE 3.0 score showed excellent discriminatory properties with an area under the receiver operating characteristic curve (AUC) for in-hospital death of 0.89 (95% CI, 0.85–0.93) in the total study cohort. Similar results were observed in Denmark (AUC 0.93, 95% CI, 0.88–0.98), Germany (AUC 0.90, 95% CI, 0.85–0.94), and Italy and Spain (AUC 0.85, 95% CI, 0.77–0.94), and Switzerland (AUC 0.93, 95% CI, 0.86–1.00). Early invasive treatment reduced the composite endpoint (absolute risk reduction: 0.12, 95% CI, 0.03–0.21, P=0.011) in patients at high risk (≥1.7%), but not in those with lower risk profiles (P interaction=0.033). Based on this new high-risk threshold, GRACE 3.0 stratified 475 (42.2%) more patients into the high-risk group, as compared to traditional GRACE risk categories (P&amp;lt;0.001). Conclusion GRACE 3.0 shows unprecedented predictive performance in patients with NSTE-ACS. In the context of a comprehensive clinical evaluation, GRACE 3.0 can support clinical decision making for the timing of invasive treatment. The high-risk group of patients with NSTE-ACS who benefit from early invasive treatment is substantially larger than previously described.ROC curve and risk groupsRestratfication towards high risk group

Baseline risk, time window, and indications for delayed percutaneous coronary interventions, their significance in treatment of ST-segment elevation myocardial infarction

The aim of the study was to estimate the significance of delayed percutaneous coronary interventions (PCIs) in the treatment of ST-segment elevation myocardial infarction (STEMI), to weigh the initial mortality risk (MR) while determining the indications for their use and the time window for the use of mechanical reperfusion in late hospital admission. Total 2226 patients admitted to the Institute with STEMI for the period 2008–2017 were studied. Emergency coronary angiography was performed in 945 admitted patients in the initial 12 hours and in 834 patients after 12–72 hours of STEMI onset; PCI was performed in 784 and 619 patients, respectively. In all patients, MR was scored by TIMI; angiographic success was assessed as TIMI 3 coronary flow and compared to ECG signs of reperfusion. The baseline MR score averaged 5 or 12.5%, being corresponded to score 4.2 or 8% in patients with PCI performed in the initial 12 hours, score 5 or 12.5% in those with PCI performed after 12–72 hours, and score 6 or 16% in patients without PCI; or with respect to the patient age, MR scored 3.7 or 7%, 6 or 16%, and 7.5 or 25%, for those under the age of 65 years, those from 65–75 years, and those over 75 years old, respectively. Mortality in patients with an early and delayed PCI was 5.2% and 4.2%, respectively, and 15.6% in patients without PCI; after patient distribution by age under 65, 65–75, and over 75 years old, the respective mortality rates were 3.8%, 4.9%, and 10.8% after an early PCI; 2.6%, 5.8%, and 8.2% after a delayed PCI; and 8.4%, 19.4%, and 28% among those without PCI. For 10 years, the number of primary PCIs had increased from 39% to 78%. The ratio of early to delayed PCI made 56% to 44%. Of 195 deaths (67 patients with PCI and 128 without PCI), 90% of patients had a three-vessel disease; 83% of patients had the MI area over 30%; and the cause of death in 84% was pulmonary edema. The presented data suggest a high practical significance of delayed PCI in patients with initially high MR, its most weighty components being the age over 75 years and severe manifestations of acute heart failure (AHF). Unlike early PCIs, the delayed PCIs are used less frequently, the initial MR is not taken into account, and they are abstained from in respect to people over 75 years of age. The reduction in mortality, proportional to the baseline MR, suggests their correlation to PCI results and the feasibility of PCI use without age restrictions. The use of primary PCIs in late hospital admissions, by analogy with early ones or selectively in high MR, will help to optimize the treatment tactics and minimize mortality.

Abstract 16234: Higher 30-Day Mortality Following Diagnostic Coronary Angiographies Performed at Community versus VA Hospitals Despite Similar Pre-Procedure Mortality Risk

Introduction: Polices to improve access increased referrals to VA community care (VACC), including diagnostic coronary angiography (DCA). Yet, studies showing higher mortality rates following percutaneous coronary intervention at VACC vs VA facilities (VAF), raise concern about VACC quality. Hypothesis: 30-day mortality following DCA would be greater at VACC vs VAF. Methods: We identified outpatient DCAs at VAF and VACC from October 2014-June 2019 (N=75,950) and were matched to balance DCAs on eight characteristics including baseline mortality risk. DCAs with same-day PCI, missing covariates or without a good match were excluded (n=33,060). Primary exposure was DCA at VACC (vs. VAF). We examined weighted characteristics of DCAs and 30-day mortality by VACC status; used weighted logistic regression, adjusting for Veterans’ age, race, rurality, insurance, distance to VAF, Elixhauser mortality risk score and presence of ischemic heart disease, to compare 30-day mortality following DCA at VACC vs VAF. We used instrumental variables analysis to explore any confounders. Results: Among 42,890 DCAs, 27% were at VACC. Weighted characteristics of DCAs were similar by VACC status; were predominantly among male, white race, older aged patients. VACC vs VAF patients had similar mean pre-DCA mortality risk scores (4.7 [SD 9.2]) vs 4.8 [SD 9.2]), respectively (SMD=-0.01). Overall, 30-day mortality was 0.9%; 2.5% at VACC and 0.4% at VAF (SMD=0.18). Overall, predicted probabilities of 30-day mortality were greater in VACC vs VAF (Figure 1).In weighted regression analysis, odds of 30-day mortality were greater in VACC vs VAF (aOR 7.07, 95% CI=4.88, 10.24, p lt0.001). Instrument variable analysis suggested selection on unobserved factors contributed to VACC assignment and mortality. Conclusions: Risk of 30-day mortality was greater following DCAs performed at VACC vs VAF, despite comparable baseline mortality risk. Further research is needed to explain this difference.

Interventions to reduce camel and small ruminant young stock morbidity and mortality in Ethiopia.

Morbidity and mortality of young stock is a challenge for livestock producers globally. In Ethiopia, where camels and small ruminants (sheep and goats) are essential smallholder and pastoral livestock, young stock losses can cause severe consequences to livelihoods. This pilot study, part of a Government-led Young Stock Mortality Reduction Consortium project, was undertaken to identify and evaluate interventions to reduce young stock mortality in mixed crop-livestock and pastoral production systems in Ethiopia. Pastoralists and mixed crop-livestock farmers were enrolled by convenience sampling across four regions. Households were sampled with questionnaire surveys to establish baseline mortality risk and prevalence of diarrhoea and respiratory disease in animals younger than one year, and followed longitudinally over a one-year period, with final evaluations conducted from March to July 2020. Mortality risk and prevalence of diarrhoea and respiratory disease before and after implementation were compared using Poisson regression models including household as random effect. Prior to intervention, median camel mortality, prevalence of diarrhoea, and respiratory disease across production systems in the different households was 0.4, 0.44 and 0.2, respectively. This compared to median pastoralist small ruminant mortality risk and prevalence of diarrhoea and respiratory disease of 0.45, 0.32 and 0.18, respectively. Post-intervention, median camel mortality, prevalence of diarrhoea and respiratory disease dropped to 0.1, 0.08 and 0. Similarly, more than half of the small ruminant households reported no mortality, and no cases of diarrhoea or respiratory disease. In camels, rate ratios of mortality risk, prevalence of diarrhoea, and respiratory disease post-intervention compared to the baseline were 0.41, 0.41 and 0.37. In small ruminants, rate ratios were 0.33, 0.35 and 0.46. All reductions were statistically significant (p<0.01). Generally, pastoralists experienced higher mortality and disease prevalence compared to mixed crop-livestock smallholders, and the effect of intervention was slightly higher in pastoralist households. The pilot study findings demonstrated highly significant reductions in mortality and risk of diarrhoea and respiratory disease post-interventions. However, not all households benefitted from the interventions, with a few households reporting increased mortality and morbidity. Many households had very few animals which made it challenging to measure impact and the study was conducted over a single year, without a control group, so between year effects could not be accounted for in the reductions observed. These findings should contribute to improved livestock productivity in Ethiopia.

Survivorship With Incrementally Faster Times to Primary Percutaneous Coronary Intervention (SWIFT-PPCI): A Systematic Review and Meta-Analysis

In the United States, there are approximately 750,000 ST-elevation myocardial infarction cases each year. Streamlined care and rapid delivery for primary percutaneous coronary intervention (PPCI) is associated with improved survival. This systematic review and meta-analysis aimed to generate a practical estimate of mortality savings for every notional 30-minute decrease in the time to achieving PPCI. Included studies were those that provided a specific absolute risk reduction for a specific reduction in pre-PPCI time. The eligible studies evaluated the survival benefit from pre-PPCI time savings measured in any interval ending with PPCI and commencing with objectively recorded timing, such as initial emergency call, first medical contact, or hospital arrival. Study planning called for the reporting of data as individual study results, with a pooled effect estimate of relative risk calculated with random-effects meta-analysis. A total of 1,088 records were eligible for review; 52 were reviewed in full text, with 4 studies (total patient n=235,814, overall mortality 4.7% to 7.8%) included in the final analysis. All 4 studies reported significant time-related survival benefit over the study focus window of 60 to 180minutes pre-PPCI. The number of lives saved per 100 cases for each 30-minute pre-PPCI time savings ranged from 0.8 to 1.9. The overall effect estimate generated was 0.753 (95% confidence interval 0.712 to 0.796), with acceptable heterogeneity (I2=36%). In conclusion, a pooled effect calculation estimated a 24.7% relative risk reduction for each 30minutes of time savings. For cases that underwent PPCI within 60 to 180minutes of initial presentation with known baseline mortality risk, the time savings in 30-minute epochs can be leveraged to estimate a specific number of lives saved; this may be useful for those involved in the organization of medical care who make systemwide plans and individual patient triage decisions.

Conditional survival following radical cystectomy for urothelial carcinoma of the bladder

IntroductionTraditional surveillance protocols do not adequately account for the decreasing risk of mortality over time in aggressive malignancies, such as bladder cancer. Rather, the risk of death depends on both the baseline risk of mortality and the time survived since treatment. We therefore evaluated the conditional survival of patients diagnosed with urothelial carcinoma of the bladder (UCB) following radical cystectomy (RC). Patients and methodsWe identified patients aged 18 to 75 with Charlson 0-1 and pTany pN0-3 cM0 UCB diagnosed from 2006 to 2015 in the National Cancer Database and treated with RC. The 2- and 5-year conditional overall survival (COS)—i.e., the probability of surviving an additional 2- or 5-years given a specified time survived since treatment—was estimated using the Kaplan-Meier method. Multivariable Cox regression models with landmark time analysis were used to evaluate the associations of baseline characteristics with OS over time. ResultsA total of 15,594 patients were included in the study. Median follow-up was 27.8 months. The 2- and 5-year COS for the overall cohort increased through 36 months follow-up and then plateaued. When stratified by pT and pN stage, the COS gain increased with higher pT and pN stage, demonstrating the greatest increase over time for patients with pTany N1-3 disease (5-year COS of 23% at baseline, 58% at 36-months, and 71% at 60-months). In multivariable Cox regression modeling, pT and pN stage were significantly associated with higher all-cause mortality at baseline (HR 3.27 for pT4, HR 2.57 for pT3 vs. ≤pT2; HR 2.26 for pN2-3, HR 1.77 for pN1 vs. pN0), but these associations were attenuated in magnitude with increasing landmark times of 36- and 60-months (HR 1.63 for pT4, HR 1.35 for pT3 vs. ≤pT2; HR 1.34 for pN2-3, HR 1.27 for pN1 vs. pN0). Our study is limited by the retrospective design and the lack of cancer-specific survival data. ConclusionsRisk of death after RC varies with time elapsed since treatment and disease stage. Accordingly, stage-specific COS may be used to improve prognostication and surveillance protocols.

Sex differences in mortality of older adults with falls after emergency department consultation: FALL-ER registry.

To investigate if sex is a risk factor for mortality in patients consulting at the emergency department (ED) for an unintentional fall. This was a secondary analysis of the FALL-ER registry, a cohort of patients ≥65 years with an unintentional fall presenting to one of 5 Spanish EDs during 52 predefined days (one per week during one year). We collected 18 independent patient baseline and fall-related variables. Patients were followed for 6 months and all-cause mortality recorded. The association between biological sex and mortality was expressed as unadjusted and adjusted hazard ratios (HR) with the 95% confidence interval (95% CI), and subgroup analyses were performed by assessing the interaction of sex with all baseline and fall-related mortality risk variables. Of 1315 enrolled patients (median age 81 years), 411 were men (31%) and 904 women (69%). The 6-month mortality was higher in men (12.4% vs. 5.2%, HR = 2.48, 95% CI = 1.65-3.71), although age was similar between sexes. Men had more comorbidity, previous hospitalizations, loss of consciousness, and an intrinsic cause for falling. Women more frequently lived alone, with self-reported depression, and the fall results in a fracture and immobilization. Nonetheless, after adjustment for age and these eight divergent variables, older men aged 65 and over still showed a significantly higher mortality (HR = 2.19, 95% CI = 1.39-3.45), with the highest risk observed during the first month after ED presentation (HR = 4.18, 95% CI = 1.31-13.3). We found no interaction between sex and any patient-related or fall-related variables with respect to mortality (p > 0.05 in all comparisons). Male sex is a risk factor for death following ED presentation for a fall in the older population adults aged 65 and over. The causes for this risk should be investigated in future studies.

Oxygenation thresholds for invasive ventilation in hypoxemic respiratory failure: a target trial emulation in two cohorts

BackgroundThe optimal thresholds for the initiation of invasive ventilation in patients with hypoxemic respiratory failure are unknown. Using the saturation-to-inspired oxygen ratio (SF), we compared lower versus higher hypoxemia severity thresholds for initiating invasive ventilation.MethodsThis target trial emulation included patients from the Medical Information Mart for Intensive Care (MIMIC-IV, 2008–2019) and the Amsterdam University Medical Centers (AmsterdamUMCdb, 2003–2016) databases admitted to intensive care and receiving inspired oxygen fraction ≥ 0.4 via non-rebreather mask, noninvasive ventilation, or high-flow nasal cannula. We compared the effect of using invasive ventilation initiation thresholds of SF < 110, < 98, and < 88 on 28-day mortality. MIMIC-IV was used for the primary analysis and AmsterdamUMCdb for the secondary analysis. We obtained posterior means and 95% credible intervals (CrI) with nonparametric Bayesian G-computation.ResultsWe studied 3,357 patients in the primary analysis. For invasive ventilation initiation thresholds SF < 110, SF < 98, and SF < 88, the predicted 28-day probabilities of invasive ventilation were 72%, 47%, and 19%. Predicted 28-day mortality was lowest with threshold SF < 110 (22.2%, CrI 19.2 to 25.0), compared to SF < 98 (absolute risk increase 1.6%, CrI 0.6 to 2.6) or SF < 88 (absolute risk increase 3.5%, CrI 1.4 to 5.4). In the secondary analysis (1,279 patients), the predicted 28-day probability of invasive ventilation was 50% for initiation threshold SF < 110, 28% for SF < 98, and 19% for SF < 88. In contrast with the primary analysis, predicted mortality was highest with threshold SF < 110 (14.6%, CrI 7.7 to 22.3), compared to SF < 98 (absolute risk decrease 0.5%, CrI 0.0 to 0.9) or SF < 88 (absolute risk decrease 1.9%, CrI 0.9 to 2.8).ConclusionInitiating invasive ventilation at lower hypoxemia severity will increase the rate of invasive ventilation, but this can either increase or decrease the expected mortality, with the direction of effect likely depending on baseline mortality risk and clinical context.

Criteria for comparatively evaluating efficacy of treatment for recurrent ST segment elevation myocardial infarction

Hospital mortality rate is considered one of the convincing criteria to assess the efficacy of the treatment for ST-elevation myocardial infarction (STEMI). Among the predictors of the mortality risk (MR), the age over 75 years is the most significant one. The aim of the study was to comparatively assess the treatment efficacy in patients with recurrent STEMI considering the hospital mortality with regard to the baseline MR and/or the age over 75 years in different timeframes in the period from 2008 to 2017. We studied 743 patients with recurrent STEMI admitted at our Institute clinic in the period from 2008 to 2017. The first group consisted of 312 patients hospitalized from 2008 to 2011; 51 of them were over 75 years old. PCI was performed in 71 and 51 cases in the first 12 and 12–72 hours, respectively. The second group included 157 patients who were admitted in the period from 2012 to 2014; 40 of them were over 75 years old, early and delayed PCIs were performed in 57 and 32 patients, respectively. And the third group consisted of 263 patients admitted from 2015 to 2017, among whom 128 patients were over 75 years old; early and delayed PCIs were performed to 82 and 80 patients, respectively. Baseline MR was determined by TIMI. Over 10 years, the number of primary PCIs had increased from 39 % in the first period to 62 % in the third one, and from 3 % to 32 % in patients older than 75 years old. The use of delayed PCI had doubled their total number. Meanwhile, although the angiographic success rate remained unchanged, there was no decrease in hospital mortality. The explanation for this lies in the increased proportion of the hospitalized patients over 75 years of age and higher mortality rates compared to those younger 75 years of age. So, in the older age group, the baseline MR was scored 7.5 or made 25 % by TIMI, the mortality was 18.3 %, making 11.6 % and 25.2 % when the PCI performance and non-performance were taken into account. These figures were 2 times lower among patients younger 75 years of age: initial MR was scored 5 making 12.5 % by TIMI; mortality was 9.6 %, making 6.5 % and 12.5 % for PCI and non-PCI cases, respectively. In this regard, with an increase in the number of hospitalized patients over 75 years of age, a higher number of PCIs performed, which was considered as associated with an increased treatment efficacy, may have not been accompanied by a decrease in hospital mortality. With similar evaluated parameters, the treatment efficacy turns to be higher among the patients with higher MR. The mortality reduction proportional to the baseline MR in different age groups indicates the results of interventions that are similar in their efficacy. These data indicate that the hospital mortality assessment with taking into account the baseline MR and/or age over 75 years, makes it possible to assess the efficacy of treatment for STEMI more objectively, to outline the ways for increasing its efficacy by using PCI in late admission, similar to that in early procedures used without age restrictions.

Evaluation of right ventricular strain in two separate cohorts with precapillary pulmonary hypertension.

Evaluation for right ventricular (RV)dysfunction is an important part of risk assessment in care of patients with pulmonary hypertension (PH) as it is associated with morbidity and mortality. Echocardiography provides a widely available and acceptable method to assess RV function. RV global longitudinal strain (RVGLS), a measure of longitudinal shortening of RV deep muscle fibers obtained by two-dimensional echocardiography, was previously shown to predict short-term mortality in patients with PH. The purpose of the current study was to assess the performance of RVGLS in predicting 1-year outcomes in PH. We retrospectively identified 83 subjects with precapillary PH and then enrolled 50 consecutive prevalent pulmonary arterial hypertension (PAH) subjects into a prospective validation cohort. Death as well as combined morbidity and mortality events at 1 year were assessed as outcomes. In the retrospective cohort, 84% of patients had PAH and the overall 1-year mortality rate was 16%. Less negative RVGLS was marginally better than tricuspid annular plane systolic excursion(TAPSE)as a predictor for death. However, in the prospective cohort, 1-year mortality was only 2%, and RVGLS was not predictive of death or a combined morbidity and mortality outcome. This study supports that RV strain and TAPSE have similar 1-year outcome predictions but highlights that low TAPSE or less negative RV strain measures are often false-positive in a cohort with low baseline mortality risk. While RV failure is considered the final common pathway for disease progression in PAH, echocardiographic measures of RV function may be less informative of risk in serial follow-up of treated PAH patients.

Biomarkers estimating baseline mortality risk for neonatal sepsis: nPERSEVERE: neonate-specific sepsis biomarker risk model.

Prognostic biomarker research neonatal sepsis is lacking. We assessed the utility of a validated pediatric prognostic tool called PERSEVERE II that uses decision tree methodology to predict mortality at discharge in neonates who experienced sepsis. Prospective study in a dual-center cohort of neonates with sepsis admitted between June 2020 and December 2021. Biomarker analysis was done on serum samples obtained at the time of evaluation for the event. In a cohort of 59 neonates with a mortality rate of 15.3%, PERSEVERE II was 67% sensitive and 59% specific for mortality, p 0.27. Amongst PERSEVERE II biomarkers, IL-8 showed good prognostic performance for mortality prediction with a cutoff of 300 pg/mL (sensitivity 100%, specificity 65%, negative predictive value 100%, AUC 0.87, p 0.0003). We derived a new decision tree that is neonate specific (nPERSEVERE) with improved performance compared to IL-8 (sensitivity 100%, specificity 86%, negative predictive value 100%, AUC 0.95, p < 0.0001). IL-8 and nPERSEVERE demonstrated good prognostic performance in a small cohort of neonates with sepsis. Moving toward precision medicine in sepsis, our study proposes an important tool for clinical trial prognostic enrichment that needs to be validated in larger studies. Prognostic and predictive biomarker research is lacking in the newborn intensive care unit. Biomarkers can be used at the time of evaluation for neonatal sepsis (blood culture acquisition) to identify neonates with high baseline mortality risk. Stratification is an important step toward precision medicine in neonatal sepsis.

Using national electronic health records for pandemic preparedness: validation of a parsimonious model for predicting excess deaths among those with COVID-19-a data-driven retrospective cohort study.

To use national, pre- and post-pandemic electronic health records (EHR) to develop and validate a scenario-based model incorporating baseline mortality risk, infection rate (IR) and relative risk (RR) of death for prediction of excess deaths. An EHR-based, retrospective cohort study. Linked EHR in Clinical Practice Research Datalink (CPRD); and linked EHR and COVID-19 data in England provided in NHS Digital Trusted Research Environment (TRE). In the development (CPRD) and validation (TRE) cohorts, we included 3.8 million and 35.1 million individuals aged ≥30 years, respectively. One-year all-cause excess deaths related to COVID-19 from March 2020 to March 2021. From 1 March 2020 to 1 March 2021, there were 127,020 observed excess deaths. Observed RR was 4.34% (95% CI, 4.31-4.38) and IR was 6.27% (95% CI, 6.26-6.28). In the validation cohort, predicted one-year excess deaths were 100,338 compared with the observed 127,020 deaths with a ratio of predicted to observed excess deaths of 0.79. We show that a simple, parsimonious model incorporating baseline mortality risk, one-year IR and RR of the pandemic can be used for scenario-based prediction of excess deaths in the early stages of a pandemic. Our analyses show that EHR could inform pandemic planning and surveillance, despite limited use in emergency preparedness to date. Although infection dynamics are important in the prediction of mortality, future models should take greater account of underlying conditions.

Red blood cell volume, but not platelet or plasma volume is associated with mortality in neonatal ECMO.

Blood product transfusions are necessary for critically ill neonates on extracorporeal membrane oxygenation (ECMO). Transfusions are administered in response to unstudied arbitrary thresholds and may be associated with adverse outcomes. The objective of this study was to identify relationships between blood product components and mortality in neonates receiving ECMO support for respiratory indications. A retrospective review of neonates receiving ECMO for respiratory indications from 2002 to 2019 from a single quaternary-referral neonatal intensive care unit (NICU). Demographic and outcome data and transfusion volume (ml/kg/day) were harvested from the medical record, and baseline mortality risk was assessed using NEO-RESCUERS scores. The association between volume of red blood cells (RBC), platelet, plasma transfusion rates (ml/kg/day), and mortality on ECMO were assessed after adjustment for NEO-RESCUERS score. Cox proportional hazards (CPH) competing risk model was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for each variable and mortality outcome. Among 248 neonates undergoing ECMO for respiratory failure, overall survival was 93%. RBC, platelet, and plasma volume were highly associated with mortality during ECMO in an unadjusted model. After adjusting for NEO-RESCUERS score, RBC volume was associated with increased mortality risk (HR 1.013, 95% CI 1.004-1.022, p=.0043), but platelet and plasma volume were not associated with mortality. RBC, but not platelet or plasma volume, is associated with mortality in neonates on ECMO. Our findings refute previous studies demonstrating an association between platelet volume and mortality for neonates on ECMO.