30-day Death Research Articles

Restrictive versus liberal blood transfusion strategies in patients with myocardial infarction and anemia: individual patient data meta-analysis of randomized trials

Abstract Background There are insufficient data to guide the appropriate use of red blood cell transfusion in patients with anemia and acute myocardial infarction (MI). Purpose To combine individual patient data from randomized clinical trials evaluating restrictive versus liberal transfusion strategies in patients with acute MI and anemia to generate precise estimates of treatment effects. Methods We searched all major databases to identify trials comparing restrictive versus liberal transfusion strategies in patients with acute MI and anemia (Hgb < 10 g/dl). We included studies that allocated participants to a liberal transfusion strategy that maintained hemoglobin greater than 10 g/dL or a restrictive transfusion strategy in which transfusion was administered if hemoglobin concentration was less than 8 g/dL. The primary outcome was a composite of 30-day death or MI. Secondary outcomes included 30-day death, 30-day cardiac death, and 6-month death. One-stage individual patient data meta-analyses were performed using a multilevel generalized linear model accounting for the clustering of patients within trials. Results We included 4311 participants from four trials. The primary outcome occurred in 334 patients (15.4%) in the restrictive and 296 patients (13.8%) in the liberal strategy (relative risk (RR) 1.13, 95% confidence interval (CI), 0.97 to 1.30) (figure 1). Death at 30-days occurred in 201 patients (9.3%) in the restrictive and 174 patients (8.1%) in the liberal strategy (RR 1.15; 95% CI, 0.95 to 1.39). Cardiac death at 30 days occurred in 5.5% in the restrictive strategy compared to 3.7% in the liberal strategy (RR 1.47; 95% CI, 1.11 to 1.94). Heart failure and thromboembolism occurred slightly more frequently in the liberal transfusion strategy group. Death at six months was higher in the restrictive (20.5%) compared to the liberal strategy (19.1%) (hazard ratio (HR) 1.08; 95% CI 1.05 to 1.11) (figure 2). The HR for cardiac death at 6 months was higher with a restrictive than liberal strategy (HR 1.38; 95% CI 1.08 to 1.76). In contrast, the HR for non-cardiac death at 6 months was lower with a restrictive than a liberal transfusion strategy (HR 0.89; 95% CI 0.84 to 0.94). Adjustment for baseline characteristics minimally changed the relative risk. Results for subgroups were similar except in patients without a history of renal failure whose risk of death or MI was increased with a restrictive strategy (RR 1.19; 95% CI, 1.01 to 1.39). Conclusions Pooled data from randomized trials found no significant differences for the primary outcome 30-day death or MI, but risk of cardiac death at 30 days and all cause death at 6 months was higher with a restrictive transfusion strategy. Given most outcomes favored liberal transfusion, and the risks from liberal transfusion were low, it may be prudent to use a liberal transfusion strategy in patients with acute MI and anemia.

Proenkephalin improves risk prediction in acute coronary syndromes: derivation and external validation of the KID-ACS risk score

Abstract Background Early assessment of renal and mortality risk in patients with acute coronary syndromes (ACS) is essential to guide treatment decisions according to international guidelines. Circulating proenkephalin (PENK) is a stable opioid metabolite with fast response to changes in kidney function. Purpose This study examined the predictive value of PENK for acute kidney injury (AKI) and mortality in patients presenting with acute coronary syndromes (ACS). Methods Plasma PENK levels were measured using a validated sandwich immunoassay in a prospective multicentre ACS cohort from Switzerland (n = 4 787) and in validation cohorts from the UK (n = 1 141) and Czechia (n = 920). A biomarker-enhanced risk score for simultaneous prediction of both in-hospital acute kidney injury (AKI) and 30-day death (KID-ACS score) with model coefficients adjusted to the outcome was derived and externally validated. In the development of the in-hospital AKI model, patients from one participating study centre were reserved for external validation (Swiss validation cohort). Results Circulating PENK ranked among the top predictors of renal outcomes and mortality in patients with ACS. Accounting for established risk factors and risk models, circulating PENK levels at presentation were independently associated with in-hospital AKI (per log2 increase: adjusted odds ratio [OR] 1.56, 95% CI 1.14 – 2.12, P = 0.005) and with 30-day mortality (per log2 increase: adjusted OR 2.69, 95% CI 1.89 – 3.84, P < 0.001). Dynamic changes in PENK levels within the first 12-24 hours after presentation were strongly and independently associated with in-hospital AKI (increase vs. decrease: adjusted OR 2.83, 95% CI 1.98 – 4.05, P < 0.001). The simple 6-item KID-ACS risk score for in-hospital AKI and 30-day mortality integrates PENK levels at presentation and showed an AUC of 0.72 (95% CI 0.68 – 0.76) for in-hospital AKI, and of 0.91 (95% CI 0.87 – 0.95) for 30-day mortality in the derivation cohort. Upon external validation, KID-ACS had similarly high performance for in-hospital AKI (Swiss validation cohort: AUC 0.73, 95% CI 0.70 – 0.77; Czech validation cohort: 0.74, 95% CI 0.68 – 0.80) and 30-day mortality (UK validation cohort: AUC of 0.87, 95% CI 0.82 – 0.91; Czech validation cohort: 0.91, 95% CI 0.87 – 0.94). The simple 6-item KID-ACS score was non-inferior to established risk models and significantly outperformed the CA-AKI risk score in predicting in-hospital AKI (Zurich cohort: delta AUC 0.11, 95% CI 0.07 – 0.15, P = 0.001) and the GRACE 2.0 in predicting 30-day mortality (UK cohort: delta AUC 0.05, 95% CI 0.01 – 0.09, P = 0.027). Conclusions Circulating PENK was identified as independent predictor of in-hospital AKI and 30-day mortality in patients with ACS. The simple 6-item KID-ACS risk score integrates circulating PENK levels and provides a novel tool for simultaneous assessment of renal and mortality risk in patients presenting with ACS.Independent Predictive Value PENKPerformance and validation of KID-ACS

Effect of four hemoglobin transfusion threshold strategies in patients with acute myocardial infarction and anemia: a target trial emulation using MINT trial data

Abstract Background The hemoglobin (Hgb) threshold at which red blood cell transfusion affords greatest benefit, without increasing transfusion-associated risks, is uncertain for patients with acute myocardial infarction (MI). The Myocardial Ischemia and Transfusion (MINT) trial recently showed a restrictive transfusion strategy (Hgb threshold <7-8g/dL) resulted in a 15% increased risk of 30-day all-cause death or recurrent MI (death/MI) compared with a liberal strategy (Hgb threshold <10g/dL) in 3,504 adults with acute MI and anemia. However, the transfusion effect at different Hgb thresholds remains uncertain. Purpose To better understand the gradient of effects from Hgb threshold transfusion triggers between 7g/dL and 10g/dL. We estimated the effects of four Hgb transfusion thresholds on 30-day death/MI and death in patients with acute MI and anemia. Methods We used data from the MINT trial and applied an innovative causal inference method, target trial emulation, to assess four Hgb thresholds. We emulated a hypothetical, 4-arm target trial of <10g/dL, <9g/dL, <8g/dL, and <7g/dL transfusion strategies in adults with acute MI and Hgb <10g/dL using a "cloning" procedure. The target trial protocol closely mirrored that of the MINT trial. We conducted a per-protocol analysis of the emulated target trial using censoring and inverse probability (IP) weighting; we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) by fitting pooled logistic regression models with a time-dependent intercept for time free of the outcomes. We estimated IP weighted Kaplan-Meier cumulative incidence curves under each strategy for 30-day outcomes. Results Of the MINT trial participants, 3,492 (99.7%) met eligibility criteria for the hypothetical target trial of four transfusion strategies. The unadjusted rate of 30-day death/MI was lowest in the <10g/dL strategy and highest in the <9g/dL strategy, and the rate of transfusions decreased monotonically as Hgb thresholds decreased. Relative to the <10g/dL strategy, the estimated HRs (95% CI) from the IP weighted model of 30-day death/MI were 1.07 (0.77-1.50) for the <9g/dL strategy, 1.14 (0.84-1.55) for the <8g/dL strategy, and 1.44 (0.99-2.09) for the <7g/dL strategy (Figure). A log-linear estimate over strategy thresholds between 7-10g/dL estimated a 1.12 (95% CI 1.00-1.27) times greater average risk of death/MI and a 1.12 (95% CI 0.92, 1.37) times greater average risk of death over 30 days for each 1g/dL decrease in the Hgb threshold. The IP weighted cumulative incidence curves showed similar increase in risk of death/MI as transfusion thresholds decreased throughout 30 days post-randomization. Conclusions Relative to a <10g/dL transfusion strategy, we estimated a progressively greater risk of 30-day death/MI as transfusion Hgb thresholds decreased within the range of 7-10g/dL. Targeting a Hgb concentration of 10g/dL in patients with a recent acute MI may avoid serious risks associated with anemia.Hazard ratios for 30-day death/MI

Identifying low-risk chest pain in out-of-hours primary care: the diagnostic performance of preHEAR and preHEART scores based on two European cohorts

Abstract Background Distinguishing cardiac from non-cardiac acute chest pain presents a diagnostic challenge. Risk stratification tools, such as the HEART score, have been developed for decision support for hospital-based settings. For prehospital settings, the preHEART score was developed as an alternative to the HEART score, with refinements made to meet prehospital conditions, as illustrated in Figure 1. While promising for use by emergency medical services, the diagnostic performance in primary care is unknown. Purpose In this study, we aim to evaluate the preHEART score (with and without high-sensitivity cardiac troponin (hs-cTn)) as a risk stratification tool to rule out acute myocardial infarction (MI) in patients evaluated in out-of-hours primary care. Methods We relied on retrospective data from two cohorts, namely, the OUT-ACS study involving 1,711 consecutive patients (47.7% female, median age: 56 (25th-75th percentiles: 45-68)) evaluated at a Norwegian primary care emergency centre from 2016-2018; and the TRACE study involving 664 consecutive patients (56.9% female, median age: 48 (25th-75th percentiles: 32-67) from a Dutch primary care emergency centre in 2017. We evaluated the preHEAR (OUT-ACS & TRACE without hs-cTn) and preHEART scores (OUT-ACS). The threshold of ≤3 points was considered low-risk and previously determined as optimal for rule-out purposes. The primary outcome was the diagnostic performance for ruling out MI at the index episode, and the secondary outcome was the composite of 90-day all-cause death or MI. Results In the OUT-ACS cohort, 61 (3.6%) patients were diagnosed with an MI; for the TRACE study, MI was diagnosed in 20 (3.0%) patients. The percentage of patients deemed at low risk by preHEAR was 49.3% (n=843) and 82.7% (n=549) for OUT-ACS and TRACE, respectively. For preHEART, only 33.6% (n=575) of OUT-ACS patients were deemed low-risk. As shown in Figure 2, the corresponding sensitivity/specificity indices for index MI were 63.9%/49.8% (OUT-ACS) and 65.0%/84.2% (TRACE) for preHEAR and 93.4%/34.6% for preHEART. Positive predictive values were low (preHEAR 5.0-11.3%, preHEART 5.0%), whereas negative predictive values were high (preHEAR 97.4-98.7%, preHEART 99.3%). For the secondary outcome, similar diagnostic performance metrics were found. All missed MI cases (n=4) in the low-risk preHEART group were female. Conclusion The preHEAR and preHEART scores did not result in adequate rule-out safety for an emergency primary care setting despite a low a priori MI risk. Moreover, the score appears to underestimate the risk for MI in females.preHEAR(T) risk scoresPerformance of the risk scores

Effects of restrictive vs liberal transfusion strategies on mortality in patients with acute myocardial infarction and anemia: The 6-month follow up primary results of the MINT trial

Abstract Background The Myocardial Ischemia and Transfusion (MINT) trial identified a statistically non-significant increase in risk of 30-day death or myocardial infarction (MI) (primary endpoint) and all-cause death and a statistically significant increase in cardiac death in patients with an acute MI and anemia assigned to a restrictive transfusion strategy compared to a liberal transfusion strategy. Purpose To determine the effect of a restrictive versus a liberal transfusion strategy on all-cause and cause-specific death 6-months post-randomization (secondary endpoint). Methods The MINT trial randomized 3,504 patients with MI and hemoglobin <10 g/dL to a restrictive (hemoglobin threshold of 7 or 8 g/dL) or liberal (hemoglobin threshold of <10 g/dL) transfusion strategy implemented during the index hospitalization. Sites contacted patients at 30-days and 6-months post-randomization and recorded patient vital status, date of death, and site-reported cause of death (categorized as cardiac, non-cardiac, or unknown). A competing risk analysis (cumulative incidence estimation and Fine-Gray models) was conducted to estimate the effect of transfusion strategy on all-cause and cause-specific death. Results Patients were enrolled from 6 countries between 2017 and 2023; average age was 72 years, and 46% were female. Vital status at 6-months was obtained for 3419 (97.6%) randomized patients (restrictive: 98.1%; liberal: 97.0%); 2,690 (76.8%) patients were alive and 729 (20.8%) had died. At 6-months, all-cause death occurred in 376 patients in the restrictive arm (21.7%) and 353 in the liberal arm (20.5%), hazard ratio [HR]: 1.07, 95% CI: 0.93–1.24. Compared to the liberal arm, a greater proportion of deaths in the restrictive arm were cardiac (41.8% vs. 29.8%). The risk of cardiac death was significantly higher in patients in the restrictive arm (9.0% vs. 6.1%, HR: 1.52; 95% CI: 1.19–1.94) whereas risk of non-cardiac death (HR: 0.87; 95% CI: 0.70–1.08) and unknown cause of death (HR: 0.88; 95% CI: 0.64–1.21) did not differ between the restrictive and the liberal arms. Conclusions In patients with acute MI and anemia, the 6-month incidence of all-cause death did not differ with a restrictive versus a liberal transfusion strategy. However, the numerically higher rate of all-cause mortality, seen with the restrictive strategy at 30-days, persisted through 6-months and was driven by cardiac causes. The long-term findings from the MINT trial suggest that a restrictive transfusion strategy may be harmful for patients with MI and anemia.

A liberal blood transfusion strategy is safe in patients with myocardial infarction, anemia, and heart failure: lessons from MINT

Abstract Background In patients with acute myocardial infarction (MI) and anemia, the Myocardial Ischemia and Transfusion (MINT) trial found a trend toward increased 30-day death or recurrent MI with a restrictive compared with a liberal blood transfusion strategy. Patients with and without heart failure (HF) may respond differently to blood transfusion. Purpose To characterize the effects of restrictive vs. liberal transfusion strategies on clinical outcomes in patients with MI and anemia with and without baseline HF. Methods In the MINT trial, 3504 patients with MI and hemoglobin <10 g/dL were randomized to restrictive (7-8 g/dL) or liberal (10 g/dL) transfusion thresholds. We compared outcomes between patients with and without baseline HF, defined as any history of HF, acute HF, or baseline left ventricular ejection fraction (LVEF) <45%. Outcomes included death or incident HF, death or recurrent MI, death, and incident HF, all at 30 days. Results Compared with patients without baseline HF (n=1633), patients with baseline HF (overall n=1871 (history of HF n=1066, acute HF n=780, LVEF <45% n= 1099) were older, more frequently male and Black, and had higher rates of prior PCI, diabetes, and hypertension. In the restrictive strategy, patients with and without baseline HF received an average of 0.63 and 0.80 units of blood and had a median LOS of 6 and 4 days, respectively. In the liberal strategy, patients with and without baseline HF received an average of 2.44 and 2.49 units of blood and had a median LOS of 5 and 4 days, respectively. Patients with baseline HF had higher rates of death or incident HF (18.0% vs. 10.0%, risk ratio [RR]=1.79 [95% confidence interval {CI} 1.50-2.13]), death or recurrent MI (17.6% vs. 13.5%, RR=1.31 [95% CI 1.12-1.53]), and death (10.5% vs. 7.5%, RR 1.41 [95% CI 1.14-1.75]). Among patients with baseline HF, a restrictive transfusion strategy resulted in a trend toward an increase in death or HF and death or MI compared with a liberal transfusion strategy (Table, Figure). Among patients without baseline HF, the risk of incident HF was lower with restrictive than with liberal transfusion strategy. Conclusions Among patients with MI and anemia, a restrictive transfusion strategy resulted in a greater increase in death or HF, death or MI, and death in patients with baseline HF than in patients without baseline HF. A liberal transfusion strategy is safe for patients with MI and anemia, including those with prior or acute HF.TableFigure

Development of a heat mortality surveillance approach for England

Abstract Background England’s unprecedented temperatures in 2022 and 2023 highlighted the severe risks of rising global temperatures on public health. This study considers the impact of heatwave events on mortality rates, supporting the development of improved health surveillance and intervention strategies. Methods Firstly, heat-associated mortality for each heat episode was estimated by comparing observed daily mortality values with the expected baseline of daily deaths. Secondly, the historic temperature-mortality relationship was established at national and regional levels using a distributed lag non-linear model with temperature and mortality data from the previous 5 years. Finally, modelled estimates of heat-associated excess mortality were generated based on the historic temperature-mortality relationships, to assess any difference between observed and modelled estimates. Results In 2022 which saw record-breaking maximum temperatures in the UK, an estimated 2,985 (2,258-3,712) heat-associated deaths were recorded across five heat episodes, the highest annual count to date. Despite relatively cool temperatures, 2023 saw the third-highest heat-associated mortality since reporting began in 2016 of 2,295 (1,681-2,910). Comparisons between modelled and observed mortality were generally similar, but showed statistically significant discrepancies for certain heat episodes across the two summers. Conclusions Heatwaves have a rapid and clear impact on health, emphasising the need for effective early warning systems and interventions. The comparison of observed mortality with predictions from historic temperature-mortality relationships at regional level demonstrates the need for a nuanced approach to surveillance and health protection for adverse heat, with factors other than temperature also playing a critical role in health impacts. This will inform continuous improvements in England’s impact-based Heat Health Alerting system. Key messages • Heatwaves pose a significant risk to public health, as evidenced by the unprecedented excess deaths during the record-breaking temperatures in England in Summer 2022. • Comparison of observed mortality with predictions from historic data can provide insight into contextual factors modulating the health impacts of heat, and inform future surveillance and response.

Early outcomes of robotic versus video-thoracoscopic anatomical segmentectomy: a propensity score-matched real-world study.

Minimally invasive anatomic segmentectomy for the resection of pulmonary nodules has significantly increased in the last years. Nevertheless, there is limited evidence on the safety and feasibility of robotic segmentectomy compared to video-assisted thoracic surgery. This study aimed to compare the real-world early outcomes of robotic and video-thoracoscopic in anatomic segmentectomy. Single centre cohort study including all consecutive patients undergoing segmentectomy by either robotic or video-thoracoscopic from June 2018 to November 2023. Propensity score case matching analysis generated two matched groups undergoing robotic or video-thoracoscopic segmentectomy. Short-term outcomes were analysed and compared between groups. 204 patients (75 robotic and 129 video-thoracoscopic patients) were included. After matching, 146 patients (73 cases in each group) were compared. One 30-day death was observed in the robotic group (P = 1). Two conversions to thoracotomy occurred in the robotic, and none in the video-thoracoscopic group (P = 0.5). Surgical time was longer in the robotic group (P = 0.091). There were no significant differences between robotic and video-thoracoscopic groups in postoperative complications (13.7% vs 15.1%, P = 1), cardiopulmonary complications (6.8% vs 6.8%, P = 1), major complications (4.1% vs 4.1%, P = 1), prolonged air leak (4.1% vs 5.5%, P = 1), arrythmia (1.4% vs 0%, P = 1) and reoperation (2.7% vs 2.7%, P = 1). Median length of stay was 3 days (IQR, 2-3 days) in the robotic group vs 3 days (IQR, 2.5-4 days) in the video-thoracoscopic group (P = 0.212). Robotic segmentectomy is a safe and feasible alternative to video-thoracoscopy, as no significant differences in early postoperative outcomes were found between the two techniques.

Quality in Acute Stroke Care (QASC) Germany: improving efficiency in stroke care with nurse-initiated FeSS-protocols

BackgroundNurse-initiated supported implementation of protocols to manage fever, hyperglycaemia (sugar) and swallowing (FeSS) following acute stroke reduced 90-day death and disability in the landmark Australian Quality in Acute Stroke Care (QASC)-Trial. An international interprofessional collaboration sought to evaluate the effects of nurse-led FeSS implementation on FeSS Protocol adherence in German stroke units.MethodsThis pre-test/post-test study was conducted in eight German stroke units between 2020 and 2022. Stroke nurses as clinical champions, supported by the project team, conducted multidisciplinary workshops discussing pre-implementation medical record audit results, barriers and facilitators to FeSS Protocol implementation, developed action plans and provided education, with ongoing support from Australia. Medical record audit data were collected by nurses, pre-implementation and three months post-implementation.ResultsIn 771 (pre-implementation) and 679 (post-implementation) patients there were improvements in overall FeSS adherence (pre 20%, post 28%; adjusted difference in proportions (95% CI) 11%, (5.1%, 16%); p < 0.001), adherence to hyperglycaemia (pre 43%, post 55%; adjusted difference 23%, (17%, 29%); p < 0.001) and swallowing (pre 52%, post 61%; adjusted difference 11%, (5.2%, 17%); p < 0.001) but not fever protocol (pre 76%, post 78%; adjusted difference 1.5%, (-2.6%, 5.7%); p = 0.474). Improvements also were noted in administration of anti-pyretics (pre 29%, post 59%; adjusted difference 32%, (20%, 44%); p < 0.001); and insulin (pre 41%, post 60%; adjusted difference 14%, (1.1%, 28%); p < 0.034) both within one hour, as well as in performing a swallow screen within 24 h of admission (pre 65%, post 74%; adjusted difference 18% (8.8%, 26%); p < 0.001).ConclusionsSupported implementation of the FeSS Protocols significantly improved acute care for post stroke complications of fever, hyperglycaemia and dysphagia in terms of higher adherence and shorter time to treatment.Trial registrationAs this is a pre-test/post-test study and does not meet the WHO/ICMJE definition of a clinical trial, registration was not required.

A Quality Improvement Initiative for Inpatient Advance Care Planning

The Centers for Medicare & Medicaid Services (CMS) implemented advance care planning (ACP) billing codes in 2016 to encourage practitioners to conduct and document ACP conversations, and included ACP as a quality metric in the CMS Bundled Payments for Care Improvement Initiative in 2018. Use of this billing code in the inpatient setting has not been studied. To determine whether a quality improvement intervention to increase inpatient ACP is effective in increasing ACP billing rates or changing hospital treatment plans or patient outcomes. This nationwide cohort study and difference-in-differences analyses compared changes in ACP billing, treatment, and outcomes in Medicare fee-for-service beneficiaries aged 65 years and older who were hospitalized and cared for by 3 different groups: practitioners employed by a national acute care staffing organization who underwent an ACP quality improvement intervention, nonintervention practitioners at the same hospital, and control group practitioners from other hospitals. Using data from the Master Beneficiary Summary File, acute care hospital stays for nonsurgical conditions were linked to Medicare enrollment, claims, and vital status data from 1-year preadmission to 1-year postadmission from 2015 to 2019. The ACP billing rates for each group were assessed for associations with 6 inpatient treatments and 4 outcomes. Data analyses were performed from January 2022 to December 2024. Billed ACP conversations, receipt of intensive care and life support (intensive care unit admission, gastrostomy tube placement, mechanical ventilation, tracheostomy), treatment limitations (newly initiated do-not-resuscitate orders) and outcomes (discharge to hospice, inpatient death, 30-day postadmission death, and 1-year postadmission death). The total study sample included 109 intervention hospitals, 1691 control hospitals, nearly 12 million Medicare fee-for-service beneficiaries aged 65 years and older, and 738 309 practitioners associated with admissions from 2016 to 2018. ACP billing rates increased more for the intervention (1.3% in preintervention to 14.0% in postintervention; P < .001) than for the nonintervention (same hospitals) and control groups (odds ratio [OR], 2.6; 95% CI, 1.7-4.1 intervention vs control). Increased ACP billing rates were significantly associated with decreased rates of inpatient death in the intervention group (OR, 0.95; 95% CI, 0.90-1.00) compared to the nonintervention (OR, 1.10; 95% CI, 1.04-1.17) and control groups (reference). All other associations were nonsignificant. This nationwide cohort study suggests that while the ACP quality initiative increased ACP billing, changes in clinical outcomes were inconsistent with the hypotheses. Further study is needed to address questions regarding confounding by unobserved measures of care quality.

Effect of Four Hemoglobin Transfusion Threshold Strategies in Patients With Acute Myocardial Infarction and Anemia : A Target Trial Emulation Using MINT Trial Data.

The optimal hemoglobin threshold to guide red blood cell (RBC) transfusion for patients with acute myocardial infarction (MI) and anemia is uncertain. To estimate the efficacy of 4 individual hemoglobin thresholds (<10 g/dL [<100 g/L], <9 g/dL [<90 g/L], <8 g/dL [<80 g/L], and <7 g/dL [<70 g/L]) to guide transfusion in patients with acute MI and anemia. Prespecified secondary analysis of the MINT (Myocardial Ischemia and Transfusion) trial using target trial emulation methods. (ClinicalTrials.gov: NCT02981407). 144 clinical sites in 6 countries. 3492 MINT trial participants with acute MI and a hemoglobin level below 10 g/dL. Four transfusion strategies to maintain patients' hemoglobin concentrations at or above thresholds of 10, 9, 8, or 7 g/dL. Protocol exceptions were permitted for specified adverse clinical events. Data from the MINT trial were leveraged to emulate 4 transfusion strategies and estimate per protocol effects on the composite outcome of 30-day death or recurrent MI (death/MI) and 30-day death using inverse probability weighting. The 30-day risk for death/MI was 14.8% (95% CI, 11.8% to 18.4%) for a <10-g/dL strategy, 15.1% (CI, 11.7% to 18.2%) for a <9-g/dL strategy, 15.9% (CI, 12.4% to 19.0%) for a <8-g/dL strategy, and 18.3% (CI, 14.6% to 22.0%) for a <7-g/dL strategy. Absolute risk differences and risk ratios relative to the <10-g/dL strategy for 30-day death/MI increased as thresholds decreased, although 95% CIs were wide. Findings were similar and imprecise for 30-day death. Unmeasured confounding may have persisted despite adjustment. The 30-day risks for death/MI and death among patients with acute MI and anemia seem to increase progressively with lower hemoglobin concentration thresholds for transfusion. However, the imprecision around estimates from this target trial analysis precludes definitive conclusions about individual hemoglobin thresholds. National Heart, Lung, and Blood Institute.

Evaluation of an emergency department-based approach to reduce subsequent opioid overdoses.

The purpose of this study was to determine the association of a multi-pronged treatment program in emergency department (ED) patients with an acute presentation of opioid use disorder (OUD) on the rate of subsequent opioid overdose (OD). This approach included ED-initiated take-home naloxone, prescription buprenorphine, and an ED-based peer support and recovery program. This was a retrospective observational analysis of adult patients presenting to the ED at a large urban hospital system from November 1, 2017 to March 17, 2023. Patients with an ED discharge diagnosis of OD or OUD were included. Outcomes determined were subsequent 90-day OD and 180-day OD death. Post hoc analyses were performed to identify intervention utilization throughout the study period including the COVID-19 pandemic as well as ED characteristics associated with subsequent OD and OD death. Statistical comparisons were made using logistic regression and chi-squared test. A total of 2634 patients presented to the ED with an opioid OD or diagnosis of OUD. Subsequent 90-day OD decreased significantly over time (11.5%-2.3%, odds ratio [OR] 0.85, confidence interval [CI] 0.82-0.89). No single intervention was independently associated with 90-day OD or 180-day OD death. Resource utilization was stable during the COVID-19 pandemic and increased afterward. A higher buprenorphine fill-rate among all patients and the Back race subgroup was associated with a decrease in 90-day OD. Subsequent OD and OD death decreased over time after implementation of a multi-pronged treatment program to ED patients with OUD. No single intervention was associated with a decrease of subsequent OD or OD death.

Rapid Acute Coronary Syndrome Evaluation Over One Hour With High-Sensitivity Cardiac Troponin I: A United States-Based Stepped-Wedge, Randomized Trial

The real-world effectiveness and safety of a 0/1-hour accelerated protocol using high-sensitivity cardiac troponin (hs-cTn) to exclude myocardial infarction (MI) compared to routine care in the United States is uncertain. The objective was to compare a 0/1-hour accelerated protocol for evaluation of MI to a 0/3-hour standard care protocol. The RACE-IT trial was a stepped-wedge, randomized trial across 9 emergency departments (EDs) that enrolled 32,609 patientsevaluated for possible MI from July 2020 through April 2021. Patients undergoing high-sensitivity cardiac troponin I testing with concentrations less than or equal to 99th percentile were included. Patients who had MI excluded by the 0/1-hour protocol could be discharged from the ED. Patients in the standard care protocol had 0- and 3-hour troponin testing and application of a modified HEART score to be eligible for discharge. The primary endpoint was the proportion of patients discharged from the ED without 30-day death or MI. There were 13,505 and 19,104 patients evaluated in the standard care and accelerated protocol groups, respectively, of whom 19,152 (58.7%) were discharged directly from the ED. There was no significant difference in safe discharges between standard care and the accelerated protocol (59.5% vs 57.8%; adjusted odds ratio (aOR)=1.05, 95% confidence interval [CI] 0.95 to 1.16). At 30 days, there were 90 deaths or MIs with 38 (0.4%) in the standard care group and 52 (0.4%) in the accelerated protocol group (aOR=0.84, 95% CI 0.43 to 1.68). A 0/1-hour accelerated protocol using high-sensitivity cardiac troponin I did not lead to more safe ED discharges compared with standard care.

Gender differences in the management and outcomes of acute coronary syndrome in indians: A systematic review and meta-analysis

BackgroundGender differences in acute coronary syndrome (ACS) outcomes have been noted in global data, which however did not analyse Indian data. No prior systematic review and meta-analysis (SRM) has addressed this important aspect of gender bias in Indian women with ACS. Hence this SRM aimed to address this knowledge gap. MethodsElectronic databases were searched for studies in ACS comparing cardiovascular disease presentation, treatment received and outcomes in women and men from India. Primary outcomes were to evaluate gender-differences in 30-day death and major adverse cardiovascular events (MACE). Secondary outcomes were to evaluate gender-differences in presentation, management and mortality. The SRM is registered with PROSPERO (CRD42023477286). ResultsFrom initially screened 3753 articles, data from 9 studies (61,185 patients) were analysed. Women with ACS had higher prevalence of diabetes [Odds ratio (OR) 1.65(95%CI:1.33–2.04); p < 0.001; I2 = 95 %] and hypertension [OR2.06(95%CI:1.88–2.25); p < 0.001; I2 = 42 %]. Smoking was significantly lower in women [OR 0.05(95%CI:0.03–0.07); p < 0.001; I2 = 87 %]. Non-ST elevation myocardial infarction (NSTEMI) was significantly higher in women [OR 1.92(95%CI:1.66–2.21); p < 0.001; I2 = 0 %]. Diagnostic angiography [OR 0.64(95%CI:0.56–0.74); p < 0.001; I2 = 46 %] and percutaneous coronary interventions [OR0.71(95%CI:0.55–0.92); p = 0.01; I2 = 92 %] were significantly lower in women. Women had significantly higher 30-day mortality [Hazard ratio (HR)2.26(95%CI:2.01–2.55); p < 0.001; I2 = 6 %], 1-year mortality [HR2.41(95%CI:1.89–3.07); p < 0.001; I2 = 53 %], in-hospital death [HR1.88(95%CI:1.19–2.96); p = 0.007; I2 = 92 %], stroke [HR 1.84 (95%CI:1.34–2.52); p < 0.001; I2 = 0 %] and MACE outcomes [OR 2.05 (95%CI:1.78–2.35); p < 0.001]. Use of aspirin, clopidogrel, beta-blockers and nitrates were significantly lower in women. ConclusionOur study highlights worse outcomes in Indian women with ACS. Higher burden of diabetes and hypertension, decreased used of PCI and lesser aggressive pharmacotherapy may be some of the contributing factors.

The High-Sensitivity HEART Pathway Safely Reduces Hospitalizations Regardless of Sex or Race in a Multisite Prospective US Cohort.

The high-sensitivity HEART pathway (hs-HP) risk stratifies emergency department (ED) patients with chest pain. It is unknown if its safety and effectiveness vary by sex or race. We conducted a subgroup analysis of the hs-HP implementation study, a pre-post interrupted time series at five US EDs. The pre-implementation period (January 2019 to April 2020) utilized the traditional HEART pathway with contemporary troponin (Siemens) and the post-implementation period (November 2020 to February 2022) used the hs-HP using hs-cTnI (Beckman Coulter). Patients were risk-stratified using the hs-HP to rule-out, observation, and rule-in groups. Safety and effectiveness outcomes were 30-day all-cause mortality or myocardial infarction (MI) and 30-day hospitalization. Twenty-six thousand and one hundred twenty-six patients were accrued (12 317 pre- and 13 809 post-implementation), of which 35.3% were non-White and 52.7% were female. Among 9703 patients with complete hs-HP assessments, 48.6% of White and 55.4% of non-White patients were ruled-out (p < 0.001). Additionally, 47.3% of males and 54.4% of females were ruled-out (p < 0.001). Among rule-out patients, 0.3% of White versus 0.3% of non-White patients (p = 0.98) and 0.3% of females versus males 0.3% (p = 0.90) experienced 30-day death or MI. Post-implementation, 30-day hospitalization decreased 17.2% among White patients (aOR 0.49, 95% CI: 0.45-0.52), 14.1% among non-White patients (aOR 0.53, 95% CI: 0.48-0.59), 15.6% among females (aOR 0.50, 95% CI: 0.46-0.54), and 16.6% among males (aOR 0.51, 95% CI: 0.47-0.56). The interactions for 30-day hospitalization between hs-HP implementation and race (p = 0.10) and sex (p = 0.69) were not significant. The hs-HP safely decreases 30-day hospitalizations regardless of sex or race. However, it classifies more non-White patients and women to the rule-out group.

An assessment of excess mortality during the COVID-19 pandemic, a retrospective post-mortem surveillance in 12 districts – Zambia, 2020–2022

BackgroundThe number of COVID-19 deaths reported in Zambia (N = 4069) is most likely an underestimate due to limited testing, incomplete death registration and inability to account for indirect deaths due to socioeconomic disruption during the pandemic. We sought to assess excess mortality during the COVID-19 pandemic in Zambia.MethodsWe conducted a retrospective analysis of monthly-death-counts (2017–2022) and individual-daily-deaths (2020–2022) of all reported health facility and community deaths at district referral health facility mortuaries in 12 districts in Zambia. We defined COVID-19 wave periods based on a sustained nationally reported SARS-CoV-2 test positivity of greater than 5%. Excess mortality was calculated as the difference between observed monthly death counts during the pandemic (2020–2022) and the median monthly death counts from the pre-pandemic period (2017–2019), which served as the expected number of deaths. This calculation was conducted using a Microsoft Excel-based tool. We compared median daily death counts, median age at death, and the proportion of deaths by place of death (health facility vs. community) by wave period using the Mann-Whitney-U test and chi-square test respectively in R.ResultsA total of 112,768 deaths were reported in the 12 districts between 2020 and 2022, of which 17,111 (15.2%) were excess. Wave periods had higher median daily death counts than non-wave periods (median [IQR], 107 [95–126] versus 96 [85–107], p < 0.001). The median age at death during wave periods was older than non-wave periods (44.0 [25.0–67.0] versus 41.0 [22.0–63.0] years, p < 0.001). Approximately half of all reported deaths occurred in the community, with an even greater proportion during wave periods (50.6% versus 53.1%, p < 0.001), respectively.ConclusionThere was excess mortality during the COVID-19 pandemic in Zambia, with more deaths occurring within the community during wave periods. This analysis suggests more COVID-19 deaths likely occurred in Zambia than suggested by officially reported numbers. Mortality surveillance can provide important information to monitor population health and inform public health programming during pandemics.

Cardiovascular outcomes in Parkinson’s disease patients from a retrospective cohort study

Parkinson’s disease (PD) reports high rates of morbidity and mortality, but the risk of adverse cardiovascular outcomes in patients with PD has not been fully elucidated. This bi-center retrospective cohort study using the electronic health records (EHR) database of two tertiary hospitals screened a total of 327,292 subjects who visited the outpatient clinic, and 1194 patients with PD were propensity score-matched with a control population. The primary outcome was the occurrence of major adverse cardiovascular events (MACE). Key secondary outcomes included all-cause death, cardiovascular (CV) death, stroke, myocardial infarction (MI), heart failure hospitalization and 30-day CV death. After PS matching, MACE occurrence was not significantly different between PD and non-PD groups (18.2% vs. 17.5%, log-rank p = 0.98). Key secondary outcomes were also similar between the two groups. In patients with PD, MACE rate, and also CV risk score, were higher in patients with more severe PD (according to Hoehn and Yahr scale and unified Parkinson’s disease rating scale), and after multivariable analysis, PD severity was not an independent predictor of MACE. Patients with PD are at an increased risk of adverse cardiovascular outcomes, but the contribution from other common CV risk factors cannot be ignored. The management of prevalent CV risk factors is therefore important in mitigating adverse outcomes among patients with PD.

Elevated serum albumin-to-creatinine ratio as a protective factor on clinical outcomes among critically ill patients with sepsis: a retrospective study.

The aim of this study was to examine the prognostic significance of serum albumin-to-creatinine ratio (ACR) in critically ill patients with sepsis. This retrospective study analyzed sepsis cases admitted to the Affiliated Hospital of Jiangsu University between January 2015 and November 2023. The patients were divided into four groups based on their ACR upon admission to the intensive care unit (ICU). Laboratory data were collected at the time of ICU admission, and the primary outcome measure was in-hospital all-cause mortality. Kaplan-Meier survival curves were generated to illustrate the differences in 30-/60-day mortality among the various groups. Multivariate Cox regression models and restricted cubic splines (RCS) were utilized to explore the association between ACR and all-cause mortality in sepsis patients. Subgroup analyses were conducted to examine the impact of other covariates on the relationship between ACR and all-cause mortality. A total of 1,123 eligible patients were included in the study, with a median ACR of 0.169. The in-hospital mortality rate was 33.7%, the ICU mortality rate was 31.9%, and the 30-day mortality rate was 28.1%. Kaplan-Meier survival analysis demonstrated that patients with higher ACR had a significantly lower risk of 30-/60-day mortality (log-rank p < 0.001). Multivariable Cox proportional hazards analyses revealed that ACR was an independent predictor of in-hospital death (HR: 0.454, 95% CI 0.271-0.761, p = 0.003), ICU death (HR: 0.498, 95% CI 0.293-0.847, p = 0.010), and 30-day death (HR: 0.399, 95% CI 0.218-0.730, p = 0.003). For each 1-unit increase in ACR, there was a 1.203-fold decrease in the risk of death during the hospital stay. The RCS curve illustrated a non-linear negative correlation between ACR and in-hospital mortality (p for non-linear =0.018), ICU mortality (p for non-linear =0.005), and 30-day mortality (p for non-linear =0.006). Sensitivity analysis indicated consistent effect sizes and directions in different subgroups, confirming the stability of the results. Low ACR levels were identified as independent risk factors associated with increased in-hospital, ICU, and 30-day mortality in sepsis patients. ACR can serve as a significant predictor of the clinical outcome of sepsis.

Clinical and utilization outcomes with short stay units vs hospital admission for lower risk decompensated heart failure: a systematic review and meta-analysis.

With over 1 million primary heart failure (HF) hospitalizations annually, nearly 80% of patients who present to the emergency department with decompensated HF (DHF) are hospitalized. Short stay units (SSU) present an alternative to hospitalization, yet the effectiveness of the SSU strategy of care is not well known. This study is to determine the effectiveness of a SSU strategy compared with hospitalization in lower-risk patients with DHF. Our primary outcome was a composite of 30-day mortality and re-hospitalization. Key secondary outcomes included 90-day mortality and re-hospitalization, costs, and 30-day days-alive-and-out-of-hospital (DAOOH). This is a systematic review and meta-analysis, following PRISMA guidelines. MEDLINE, EMBASE, CENTRAL, CINAHL, SCOPUS, and Web of Science were searched from inception through February 2024. Either randomized trials or comparative observational studies were included if they compared outcomes between low-risk ED DHF patients admitted to an SSU (defined as an observation unit with expected stay ≤ 48h) vs. admitted to the hospital. Two authors independently screened all titles and abstracts and then identified full texts for inclusion. Data extraction and risk of bias assessments were performed by two authors in parallel. The primary outcome was a composite of death or readmission within 30days, reported as relative risk (RR), where a RR < 1 favored the SSU strategy. Secondary outcomes included 90-day mortality and re-hospitalization, costs, and 1-month days-alive-and-out-of-hospital (DAOOH). Of the 467 articles identified by our search strategy, only 3 full text articles were included. In meta-analysis for the primary outcome of 30-day death or readmission, the RR was 0.95 (95% CI = 0.56 to 1.63; I2 = 0%) for patients randomized to SSU vs hospitalization (2 studies, 241 patients). There were only 2 total deaths at 30days in the 2 studies (total N = 258) which reported 30-day mortality, both in hospitalized patients. Only one study reported 90-day outcomes, showing no significant differences. Costs were lower in the SSU arm from one study, and 30-day DAOOH also favored SSU based on a single randomized trial. Based on very limited evidence, SSU provides similar efficacy for 30-day and 90-day mortality and readmission compared to hospitalization. An SSU strategy appears safe and may be cost effective.

Extensive Dysregulation of Phenylalanine Metabolism Is Associated With Stress Hyperphenylalaninemia and 30-Day Death in Critically Ill Patients With Acute Decompensated Heart Failure.

Stress hyperphenylalaninemia predicts elevated mortality rates in patients with acute decompensated heart failure (ADHF). This study investigated the metabolic pathways underlying this association and identified a unique metabolic phenotype underlying the association between stress hyperphenylalaninemia and adverse outcomes in ADHF. This was a retrospective cohort study. We enrolled 120 patients with ADHF in an intensive care unit (60 with a phenylalanine level ≥112 μM, 60 with a phenylalanine level <112 μM), and 30 controls. Plasma phenylalanine-derived metabolites were measured, and participants were evaluated for 30-day death. Patients with ADHF had extensive activations of the alternative pathways for metabolizing phenylalanine, leading to the levels of phenylalanine-derived downstream metabolites 1.5 to 6.1 times higher in patients with ADHF than in the controls (all P<0.001). Extensive dysregulation of these alternative pathways significantly increased phenylalanine levels and contributed to a distinct metabolic phenotype, characterized by increased phenylalanine, tyrosine, homogentisic acid, and succinylacetone levels but decreased benzoic acid and 3,4-dihydroxyphenylalanine levels. Throughout the 30-day follow-up period, 47 (39.2%) patients died. This distinct metabolic phenotype was associated with an increased mortality rate (odds ratio, 1.59 [95% CI, 1.27-1.99]; P<0.001). A multivariable analysis confirmed the independent association of this metabolic phenotype, in addition to phenylalanine and tyrosine levels, with 30-day death. In patients with ADHF, extensive dysregulation of the alternative pathways for metabolizing phenylalanine was correlated with stress hyperphenylalaninemia and a distinct metabolic phenotype on the phenylalanine-tyrosine-homogentisic acid-succinylacetone axis. Both stress hyperphenylalaninemia and metabolic dysregulation on this axis were associated with poor outcomes.