Absolute Mortality Reduction Research Articles

Medication use evaluation of tocilizumab implementation in COVID-19 treatment guidelines: A causal inference approach.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Introduction of new medications to health-system formularies is often not accompanied by assessments of their clinical impact on the local patient population. The growing availability of electronic health record (EHR) data and advancements in pharmacoepidemiology methods offer institutions the opportunity to monitor the medication implementation process and assess clinical effectiveness in the local clinical context. In this study, we applied novel causal inference methods to evaluate the effects of a formulary policy introducing tocilizumab therapy for critically ill patients with coronavirus disease 2019 (COVID-19). We conducted a medication use evaluation utilizing EHR data from patients admitted to a large medical center during the 6 months before and after implementation of a formulary policy endorsing the use of tocilizumab for treatment of COVID-19. The impact of tocilizumab on 28-day all-cause mortality was assessed using a difference-in-differences analysis, with ineligible patients serving as a nonequivalent control group, and a matched analysis guided by a target trial emulation framework. Safety endpoints assessed included the incidence of secondary infections and liver enzyme elevations. Our findings were benchmarked against clinical trials, an observational study, and a meta-analysis. Following guideline modification, tocilizumab was administered to 69% of eligible patients. This implementation was associated with a 3.1% absolute risk reduction in 28-day mortality (odds ratio, 0.86; number needed to treat to prevent one death, 32) attributable to the inclusion of tocilizumab in the guidelines and an additional 8.6% absolute risk reduction (odds ratio, 0.65; number needed to treat to prevent one death, 12) linked to its administration. These findings were consistent with estimates from published literature, although the effect estimates from the difference-in-differences analysis exhibited imprecision. Evaluating formulary management decisions through novel causal inference approaches offers valuable estimates of clinical effectiveness and the potential to optimize the impact of new medications on population outcomes.

Patterns of Acute Ischemic Stroke Treatment from 2010 to 2020: An Evolving Landscape in Stroke Management Following Thrombectomy Trials.

Population-based studies on stroke can help guide the care of patients with acute ischemic stroke (AIS) by providing health care communities with information regarding the current usage of stroke treatments. It remains unclear how rapidly new techniques, particularly endovascular stroke treatment (EST), are being adopted and whether there is any disparity in their availability. Although studies using the National Inpatient Sample (NIS) have been conducted, updated studies over a longer period may provide further insights. This study aimed to understand patterns of AIS treatment, discharge disposition, in-hospital mortality, and mean length of stay (LOS) for each modality from 2010 to 2020 using the NIS database. This retrospective longitudinal study was conducted using NIS data from 2010 to 2020. Patients were categorized into groups based on whether they received intravenous recombinant tissue plasminogen activator (rt-PA), EST, both rt-PA and EST (combined therapy), or supportive care alone. Demographic, socioeconomic, regional, insurance, and hospital data were also obtained. The primary outcome was the proportion of patients receiving each modality, whereas the secondary outcomes were in-hospital mortality, mean LOS, and discharge disposition. The usage rates increased (p < 0.001) in all groups between 2010 and 2020 (rt-PA: 5.09% to 8.39%, EST: 0.31% to 4.40%, and rt-PA+EST: 0.46% to 1.09%). The highest increase in usage was observed for EST, with a thirteen-fold increase. Mortality decreased from 2010 to 2020 in all groups (rt-PA: 8.45% to 3.54%, EST: 25.22% to 12.50%, and rt-PA+EST: 21.12% in 2010 to 9.30%) (p < 0.001). Combination therapy demonstrated the greatest improvement, with an 11.2% reduction in absolute mortality. Mean LOS was reduced for patients who received rt-PA (6.8 to 4.8 days), EST (9.3 to 8.9 days), and combined therapy (10.0 to 8.3 days) (p < 0.001) over the study period. The proportion of patients discharged to home increased for rt-PA (29.01% to 41.85%), EST (14.13% to 17.70%), and combined therapy (12.89% to 24.29%) (p < 0.001). Overall, stroke treatment usage was higher among the higher income groups, regardless of race. Higher usage was also observed for Whites in the West and Hispanic ethnicities in the South and West. Regardless of income or treatment method, utilization rates were lower for Black patients. Utilization rates were lower for Black patients with Medicare, Medicaid, or self-pay than for White patients. Our study demonstrated that endovascular stroke treatment continues to expand, leading to better outcomes for mortality, LOS, and home discharge. Despite these positive patterns, there are visible inequities across regions, income status, and races.

Does proactive care in care homes improve survival? A quality improvement project

BackgroundNHS England’s ‘Enhanced Health in Care Homes’ specification aims to make the healthcare of care home residents more proactive. Primary care networks (PCNs) are contracted to provide this, but approaches...

Statistical analysis plan for the replacing protein via enteral nutrition in a stepwise approach in critically ill patients (REPLENISH) randomized clinical trial

BackgroundThe optimal amount and timing of protein intake in critically ill patients are unknown. REPLENISH (Replacing Protein via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial evaluates whether supplemental enteral protein added to standard enteral nutrition to achieve a high amount of enteral protein given from ICU day five until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve a moderate amount of enteral protein would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients.MethodsIn this multicenter randomized trial, critically ill patients will be randomized to receive supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition to achieve a high amount of enteral protein (range of 2–2.4 g/kg/day) or no supplemental enteral protein to achieve a moderate amount of enteral protein (0.8–1.2 g/kg/day). The primary outcome is 90-day all-cause mortality; other outcomes include functional and health-related quality-of-life assessments at 90 days. The study sample size of 2502 patients will have 80% power to detect a 5% absolute risk reduction in 90-day mortality from 30 to 25%. Consistent with international guidelines, this statistical analysis plan specifies the methods for evaluating primary and secondary outcomes and subgroups. Applying this statistical analysis plan to the REPLENISH trial will facilitate unbiased analyses of clinical data.ConclusionEthics approval was obtained from the institutional review board, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia (RC19/414/R). Approvals were also obtained from the institutional review boards of each participating institution. Our findings will be disseminated in an international peer-reviewed journal and presented at relevant conferences and meetings.Trial registrationClinicalTrials.gov, NCT04475666. Registered on July 17, 2020.

Eligibility and Projected Benefits of Rapid Initiation of Quadruple Therapy for Newly Diagnosed Heart Failure

BackgroundU.S. nationwide estimates of the proportion of patients newly diagnosed with heart failure with reduced ejection fraction (HFrEF) eligible for quadruple medical therapy, and the associated benefits of rapid implementation, are not well characterized. ObjectivesThis study sought to characterize the degree to which patients newly diagnosed with HFrEF are eligible for quadruple medical therapy, and the projected benefits of in-hospital initiation. MethodsAmong patients hospitalized for newly diagnosed HFrEF in the Get With The Guidelines–Heart Failure registry from 2016 to 2023, eligibility criteria based on regulatory labeling, guidelines, and expert consensus documents were applied for angiotensin receptor-neprilysin inhibitor, beta-blocker, mineralocorticoid receptor antagonist, and sodium-glucose cotransporter 2 inhibitor therapies. Of those eligible, the projected effect of quadruple therapy on 12-month mortality was modeled using treatment effects from pivotal clinical trials utilized by the AHA/ACC/HFSA Guideline for the Management of Heart Failure, and compared with observed outcomes among patients treated with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and beta-blockers. ResultsOf 33,036 patients newly diagnosed with HFrEF, 27,158 (82%) were eligible for quadruple therapy, and 30,613 (93%) were eligible for ≥3 components. From 2021 to 2023, of patients eligible for quadruple therapy, 15.3% were prescribed quadruple therapy and 41.5% were prescribed triple therapy. Among Medicare beneficiaries eligible for quadruple therapy, 12-month incidence of mortality was 24.7% and HF hospitalization was 22.2%. Applying the relative risk reductions in clinical trials, complete implementation of quadruple therapy by time of discharge was projected to yield absolute risk reductions in 12-month mortality of 10.4% (number needed to treat = 10) compared with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and beta-blocker, and 24.8% (number needed to treat = 4) compared with no GDMT. ConclusionsIn this nationwide U.S. cohort of patients hospitalized for newly diagnosed HFrEF, >4 of 5 patients were projected as eligible for quadruple therapy at discharge; yet, <1 in 6 were prescribed it. If clinical trial benefits can be fully realized, in-hospital initiation of quadruple medical therapy for newly diagnosed HFrEF would yield large absolute reductions in mortality.

Temporal Trends in Mortality of Critically Ill Patients with Sepsis in the United Kingdom, 1988-2019.

Rationale: Sepsis is a frequent cause of ICU admission and mortality. Objectives: To evaluate temporal trends in the presentation and outcomes of patients admitted to the ICU with sepsis and to assess the contribution of changing case mix to outcomes. Methods: We conducted a retrospective cohort study of patients admitted to 261 ICUs in the United Kingdom during 1988-1990 and 1996-2019 with nonsurgical sepsis. Measurements and Main Results: A total of 426,812 patients met study inclusion criteria. The patients had a median (interquartile range) age of 66 (53-75) years, and 55.6% were male. The most common sites of infection were respiratory (60.9%), genitourinary (11.5%), and gastrointestinal (10.3%). Compared with patients in 1988-1990, patients in 2017-2019 were older (median age, 66 vs. 63 yr), were less acutely ill (median Acute Physiology and Chronic Health Evaluation II acute physiology score, 14 vs. 20), and more often had genitourinary sepsis (13.4% vs. 2.0%). Hospital mortality decreased from 54.6% (95% confidence interval [CI], 51.0-58.1%) in 1988-1990 to 32.4% (95% CI, 32.1-32.7%) in 2017-2019, with an adjusted odds ratio of 0.64 (95% CI, 0.54-0.75). The adjusted absolute hospital mortality reduction from 1988-1990 to 2017-2019 was 8.8% (95% CI, 5.6-12.1). Thus, of the observed 22.2-percentage point reduction in hospital mortality, 13.4 percentage points (60% of total reduction) were explained by case mix changes, whereas 8.8 percentage points (40% of total reduction) were not explained by measured factors and may be a result of improvements in ICU management. Conclusions: Over a 30-year period, mortality for ICU admissions with sepsis decreased substantially. Although changes in case mix accounted for the majority of observed mortality reduction, there was an 8.8-percentage point reduction in mortality not explained by case mix.

A national heart failure initiative is associated with improved use of quadruple guideline-directed medical therapy

Abstract Background Heart Failure (HF) is projected to impact over 8 million people in the US by 2030. The 2022 AHA/ACC/HFSA Guideline for the Management of HF recommend four foundational medication classes for treating HFrEF patients: RAAS inhibitors, preferably angiotensin receptor/neprilysin inhibitor (ARNi), evidence-based beta-blockers (EBBB), sodium-glucose cotransporter-2 inhibitor (SGLT2i) and mineralocorticoid receptor antagonist (MRA) referred to as Quadruple Guideline-Directed Medical Therapy (Q-GDMT). Q-GDMT has shown an estimated 73% relative and 26% absolute reduction in all-cause mortality over 2 years. Yet, despite remarkable clinical potential, these therapies are patently underutilized in clinical practice. It is unknown whether an implementation science strategy may enhance adherence to Q-GDMT for HF. Methods IMPLEMENT-HF (IHF) is a national HF quality improvement initiative composed of a multidisciplinary learning collaborative and resource repository across seven U.S regions. IHF promotes adherence to Q-GDMT by focusing on early adoption and rapid adherence to prescribing at hospital discharge and within 30 days post discharge. Multi-disciplinary participation in the learning collaborative includes pharmacy, provider groups, nursing, quality, social services, outpatient clinics and others. Shared interventions to promote Q-GDMT include formulary changes (e.g., adding SGLT2i), optimizing electronic health record tools (disease-specific order sets, dot phrases), clinician education, and user-friendly patient resources to address medication access. IHF sites receive educational materials, including webinars, learning modules, pocket guideline booklets, and reminder cards to reinforce Q-GDMT. IHF participating hospitals collect Q-GDMT data at discharge and at 30 days post discharge in Get With The Guidelines®-Heart Failure (GWTG-HF). These data were analyzed from baseline (Q1 Q2 2021 aggregate) through Q3 2022. Results Data from 71 IHF participating sites of 13,858 HFrEF patient hospitalization episodes (median age 69, 34% females, median LVEF 24%), demonstrated Q-GDMT prescription at discharge increased from 14% at baseline to 47% in Q3 2022 (p value &amp;lt;0.001). 30-day post discharge data from 52 IHF sites demonstrated an increase in Q-GDMT from 9% at baseline to 58% in Q3 2022 (p value &amp;lt;0.001) as seen in Figure 1. Conclusions Among sites participating in IHF, the use of an implementation science strategy suggest a rapid increase in prescribing Q-GDMT for eligible HFrEF patients at discharge and 30-days post discharge. This multi-region quality improvement initiative demonstrates the potential for this learning collaborative model to drive improvement in adherence to Q-GDMT prescribing, using shared implementation strategies to overcome barriers. Ongoing study will assess continued compliance and clinical outcomes with Q-GDMT beyond the timeframe of this analysis.Quadruple Medication Therapy baseline-Q3

Abstract 16761: Preprocedural Frailty is Associated With Lower Cardiac Rehabilitation Use Despite Greater Benefit

Introduction: Increased frailty before cardiovascular procedures is associated with poorer outcomes. While underutilized, cardiac rehabilitation (CR) is guideline-recommended for patients undergoing cardiovascular procedures and may help mitigate frailty through individualized, monitored exercise and risk factor reduction. Research Question/Hypothesis: Evaluate the relationship between preprocedural frailty, CR use, and one-year mortality. Methods: Medicare fee-for-service claims data were queried for patients who underwent inpatient percutaneous or surgical revascularization or aortic valve replacement between July 2016 and December 2018. Patients were stratified into quartiles (Q1 through Q4) using the validated claims-based frailty index. CR use was defined as attending any CR session within one year of discharge. Unadjusted and adjusted logistic regression was used to compare CR use across increasing frailty quartiles, and inverse probability treatment weighting was used to evaluate the effect of CR on one-year mortality across frailty quartiles. Results: Overall CR enrollment among the 570,851 beneficiaries was 35.3%; increasing frailty was associated with decreased CR use (unadjusted: frailty Q1: 48.3% vs Q4: 20.6%, p&lt;0.001; adjusted OR: 0.61, p&lt;0.001). Unadjusted one-year mortality was lower among CR users as opposed to non-users (2.7% vs 14.6%). After weighted adjustment, the absolute reduction in mortality associated with CR use was greater among frailer patients (Q4: -12.2%) relative to less frail patients (Q1: -2.9%) (Figure). Significant interaction effects between CR use and frailty quartiles indicated stronger associations of CR on mortality among more frail patients. Conclusions: Preprocedural frailty was associated with lower CR use despite greater absolute benefits on one-year mortality. Increasing CR enrollment in frail patients may enhance outcomes after cardiac interventions.

Radiotherapy to regional nodes in early breast cancer: an individual patient data meta-analysis of 14 324 women in 16 trials

Radiotherapy has become much better targeted since the 1980s, improving both safety and efficacy. In breast cancer, radiotherapy to regional lymph nodes aims to reduce risks of recurrence and death. Its effects have been studied in randomised trials, some before the 1980s and some after. We aimed to assess the effects of regional node radiotherapy in these two eras. In this meta-analysis of individual patient data, we sought data from all randomised trials of regional lymph node radiotherapy versus no regional lymph node radiotherapy in women with early breast cancer (including one study that irradiated lymph nodes only if the cancer was right-sided). Trials were identified through the EBCTCG's regular systematic searches of databases including MEDLINE, Embase, the Cochrane Library, and meeting abstracts. Trials were eligible if they began before Jan 1, 2009. The only systematic difference between treatment groups was in regional node radiotherapy (to the internal mammary chain, supraclavicular fossa, or axilla, or any combinations of these). Primary outcomes were recurrence at any site, breast cancer mortality, non-breast-cancer mortality, and all-cause mortality. Data were supplied by trialists and standardised into a format suitable for analysis. A summary of the formatted data was returned to trialists for verification. Log-rank analyses yielded first-event rate ratios (RRs) and confidence intervals. We found 17 eligible trials, 16 of which had available data (for 14 324 participants), and one of which (henceforth excluded), had unavailable data (for 165 participants). In the eight newer trials (12 167 patients), which started during 1989-2008, regional node radiotherapy significantly reduced recurrence (rate ratio 0·88, 95% CI 0·81-0·95; p=0·0008). The main effect was on distant recurrence as few regional node recurrences were reported. Radiotherapy significantly reduced breast cancer mortality (RR 0·87, 95% CI 0·80-0·94; p=0·0010), with no significant effect on non-breast-cancer mortality (0·97, 0·84-1·11; p=0·63), leading to significantly reduced all-cause mortality (0·90, 0·84-0·96; p=0·0022). In an illustrative calculation, estimated absolute reductions in 15-year breast cancer mortality were 1·6% for women with no positive axillary nodes, 2·7% for those with one to three positive axillary nodes, and 4·5% for those with four or more positive axillary nodes. In the eight older trials (2157 patients), which started during 1961-78, regional node radiotherapy had little effect on breast cancer mortality (RR 1·04, 95% CI 0·91-1·20; p=0·55), but significantly increased non-breast-cancer mortality (1·42, 1·18-1·71; p=0·00023), with risk mainly after year 20, and all-cause mortality (1·17, 1·04-1·31; p=0·0067). Regional node radiotherapy significantly reduced breast cancer mortality and all-cause mortality in trials done after the 1980s, but not in older trials. These contrasting findings could reflect radiotherapy improvements since the 1980s. Cancer Research UK, Medical Research Council.

Effect of Breast Screening Regimen on Breast Cancer Outcomes: A Modeling Study.

Guidelines vary for the age at which to begin breast cancer screening and the interval between examinations. A validated computer model was used to compare estimated outcomes between various screening regimens. The OncoSim-Breast microsimulation model (Canadian Partnership Against Cancer) was used to simulate a cohort of 1.53 million Canadian women born in 1975. The effect of screening regimen on absolute breast cancer mortality rates, stage at diagnosis, number needed to be screened to avert a breast cancer death or save a life year, abnormal recall rates and negative biopsy rates was examined for unscreened women or those entering screening at age 40 or 50 and screened annually or biennially to age 74. Compared to no screening, absolute mortality reduction was 4.6 (biennial 50-74), 5.9 (biennial 40-74) and 7.9 (annual 40-74) fewer deaths per 1000 women. The absolute rate of diagnosis of advanced cancers (Stage 2, 3 and 4) falls in favor of earlier stages as the number of lifetime screens increases. Annual screening beginning at age 40 until age 74 would provide an additional reduction of 2 and 3.3 breast cancer deaths per 1000 women compared to biennial screening beginning at ages 40 and 50, respectively. There is a corresponding drop in the absolute number of Stage 2, 3 and 4 cancers diagnosed.

Relationship Between Community-Level Distress and Cardiac Rehabilitation Participation, Facility Access, and Clinical Outcomes After Inpatient Coronary Revascularization.

Although disparities in cardiac rehabilitation (CR) participation are well documented, the role of community-level distress is poorly understood. This study evaluated the relationship between community-level distress and CR participation, access to CR facilities, and clinical outcomes. A retrospective cohort study was conducted on a 100% sample of Medicare beneficiaries undergoing inpatient coronary revascularization between July 2016 and December 2018. Community-level distress was defined using the Distressed Community Index quintile at the beneficiary zip code level, with the first and fifth quintiles representing prosperous and distressed communities, respectively. Outpatient claims were used to identify any CR use within 1 year of discharge. Beneficiary and CR facility zip codes were used to describe access to CR facilities. Adjusted logistic regression models evaluated the association between Distressed Community Index quintiles, CR use, and clinical outcomes, including one-year mortality, all-cause hospitalization, and acute myocardial infarction hospitalization. A total of 414 730 beneficiaries were identified, with 96 929 (23.4%) located in the first and 67 900 (16.4%) in the fifth quintiles, respectively. Any CR use was lower for beneficiaries in distressed compared with prosperous communities (26.0% versus 46.1%, P<0.001), which was significant after multivariable adjustment (odds ratio, 0.41 [95% CI, 0.40-0.42]). A total of 98 458 (23.7%) beneficiaries had a CR facility within their zip code, which increased from 16.3% in prosperous communities to 26.6% in distressed communities. Any CR use was associated with absolute reductions in mortality (-6.8% [95% CI, -7.0% to -6.7%]), all-cause hospitalization (-5.9% [95% CI, -6.3% to -5.6%]), and acute myocardial infarction hospitalization (-1.3% [95% CI, -1.5% to -1.1%]), which were similar across each Distressed Community Index quintiles. Although community-level distress was associated with lower CR participation, the clinical benefits were universally received. Addressing barriers to CR in distressed communities should be considered a significant priority to improve survival after coronary revascularization and reduce disparities.

The Footprint of Mortality: Outcome Analysis in Charcot Neuroarthropathy Patients Who Underwent Multiple Surgical Procedures

Category: Midfoot/Forefoot; Diabetes Introduction/Purpose: Charcot neuroarthropathy (CN) is a progressive degenerative disease that most commonly manifests in the foot and ankle as a result of peripheral neuroarthropathy. Primary treatment is typically management of disease progression, however, surgical procedures including arthrodesis, exostectomy, and amputation may be indicated for more refractory cases. Our prior research analyzed a subset of the current sample to evaluate patients who underwent multiple surgical procedures to manage their CN, identifying amputation to be associated with the highest all-cause mortality rate. The purpose of this study is to analyze demographic data and mortality rates from a larger sample of patients with an emphasis on the mortality associated with procedure order and type in patients who underwent multiple procedures in the management of their CN. Methods: Following IRB approval, a database of all patients at a single institution from 1/1/2000 to 1/31/2022 with CPT and ICD codes indicating a diagnosis of Charcot foot of the lower extremity who underwent amputation, exostectomy, and/or arthrodesis was created from the electronic health record. Only patients who underwent multiple procedures in the treatment of their CN were included in the study. Amputation was further classified as major (transmetatarsal amputation or above) or minor (below the metatarsal level or a single toe at the metatarsal level). Demographics including age, sex, race, and insurance status were recorded in addition to all-cause mortality rates for each procedure type and all-cause mortality rates relative to procedure order. Descriptive statistics and chi-square tests for homogeneity were conducted for analysis. One patient, identified as an outlier, had 13 procedures, and was excluded so as to not distort the statistical analysis. Results: A total of 700 individual patients who underwent at least 2 procedures were included in this study, with a total of 1902 procedures performed of which 363, 651, 459, and 429 were completed for major amputation, minor amputation, exostectomy, and arthrodesis respectively. Figure 1A describes the baseline characteristics of patients who underwent each procedure. The all- cause mortality rate remained the lowest in arthrodesis patients, regardless of the order in which it was performed. Furthermore, patients who underwent either arthrodesis or exostectomy at any point in their procedure sequence had an absolute risk reduction in all-cause mortality of 42.5% and 21.1% respectively, while both amputation groups had an absolute risk increase in all- cause mortality of 46.0% (minor) and 48.3% (major). Conclusion: For patients who underwent multiple procedures to manage their CN, those who underwent arthrodesis at any point during their procedure sequence showed the trend of having the lowest all-cause mortality rates (Figure 1D). This may indicate that early anatomic correction through arthrodesis could lead to improved mortality in Charcot patients. Figure 1E describes the significantly increased (p &lt; 0.001) mortality rates associated with both amputation groups, which further highlights the importance of early intervention and management of disease progression. Future research should aim to develop surgical treatment guidelines based on disease progression to continue to minimize mortality rates.

Mortality Trends After Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction

BackgroundObservational studies have reported that mortality rates after ST-segment elevation myocardial infarction (STEMI) have been stable since 2006 to 2010. ObjectivesThe aim of this study was to evaluate the temporal trends in 1-year, 30-day, and 31- to 365-day mortality after STEMI in Western Denmark where primary percutaneous coronary intervention (PCI) has been the national reperfusion strategy since 2003. MethodsUsing the Western Denmark Heart Registry, the study identified first-time PCI-treated patients undergoing primary PCI (pPCI) for STEMI from 2003 to 2018. Based on the year of pPCI, patients were divided into 4 time-interval groups and followed up for 1 year using the Danish national health registries. ResultsA total of 19,613 patients were included. Median age was 64 years, and 74% were male. One-year mortality decreased gradually from 10.8% in 2003-2006, 10.4% in 2007-2010, 9.1% in 2011-2014, to 7.7% in 2015-2018 (2015-2018 vs 2003-2006: adjusted HR [aHR]: 0.71; 95% CI: 0.62-0.82). The largest absolute mortality decline occurred in the 0- to 30-day period with a 2.3% reduction (aHR: 0.69; 95% CI: 0.59-0.82), and to a lesser extent in the 31- to 365-day period (risk reduction: 1.0%; aHR: 0.71; 95% CI: 0.56-0.90). ConclusionsIn a high-income European country with a fully implemented pPCI strategy, 1-year mortality in pPCI-treated patients with STEMI decreased substantially between 2003 and 2018. Approximately three-quarters of the absolute mortality reduction occurred within the first 30 days after pPCI. These results indicate that optimization of early management of pPCI-treated patients with STEMI offers great opportunities for improving overall survival in contemporary clinical practice.

Effect of the modified snorkel mask as noninvasive ventilatory support in patients with acute hypoxemic respiratory failure due to COVID-19.

The shortage of mechanical ventilators during the COVID-19 pandemic led doctors to use alternative noninvasive ventilation systems, including a modified snorkel mask. Data on the use of the modified snorkel mask is limited. The study aims to describe the effect and clinical characteristics of patients with COVID-19 treated with a snorkel mask and to investigate the factors associated with the failure to use noninvasive ventilation with a snorkel mask. In this retrospective observational study, adult patients with COVID-19 who were treated with a snorkel mask at Daniel Alcides Carrion Hospital of Huancayo-Perú were selected. Of the 390 patients included, 158 (20.5%) received noninvasive ventilation with a snorkel, 84 (53.2%) patients were discharged alive without intubation, and the mortality rate was 22%. In the control group that received standard treatment, 129 patients (55.6%) failed (i.e., deceased or admitted to a mechanical ventilator). The mortality rate was 33.2%. ROX index < 4.8, consolidation-type tomographic pattern, and the presence of complications, such as bacterial pneumonia or thromboembolism, were independently associated with a higher risk of noninvasive ventilation failure with snorkels. Using the snorkel system resulted in an absolute mortality reduction of 11%, and recovery increased by 15% compared to the standard treatment system. Therefore, this device can be used as an acceptable alternative in the absence of mechanical ventilators.

Age-stratified comparison of prognosis in cardiac resynchronization therapy with or without prophylactic defibrillator for non-ischemic cardiomyopathy - a nationwide cohort study.

Prior studies have suggested that the benefit from primary preventive defibrillator treatment for patients with non-ischemic cardiomyopathy primarily, treated with cardiac resynchronization therapy, may be age-dependent. We aimed to compare age-stratified mortality rates and mode of death in patients with non-ischemic cardiomyopathy who are treated with either primary preventive Cardiac Resynchronization Therapy-defibrillator (CRT-D) or CRT-pacemaker (CRT-P). All patients with non-ischemic cardiomyopathy and CRT-P or primary preventive CRT-D who were implanted in Sweden during the period 2005-2020 were included. Propensity scoring was used to create a matched cohort. Primary outcome was all-cause mortality within five years. 4027 patients were included, 2334 with CRT-P and 1693 with CRT-D. Crude 5-year mortality was 635 (27%) vs. 246 (15%), p < 0.001. In Cox regression analysis, adjusted for clinically relevant covariables, CRT-D was independently associated with higher five-year survival (0.72 [0.61-0.85], p < 0.001). Cardiovascular mortality was similar between groups (62% vs. 64%, p = 0.64), but death from heart failure was more common in the CRT-D group (46% vs. 36%, p = 0.007). In the matched cohort (n = 2414), five-year mortality was 21% (24% versus 16%, p < 0.001). In age-stratified analyses, CRT-P was associated with higher mortality in age-groups <60 years and 70-79 years, but there was no difference in age groups 60-69 years or 80-89 years. In this nationwide registry-based study, patients with CRT-D have better five-year survival compared to patients with CRT-P. The interaction between age and mortality reduction not consistent, but patients with CRT-D aged <60 years had the largest absolute mortality reduction.

Evaluation of the efficacy and safety of TREM-1 inhibition with nangibotide in patients with COVID-19 receiving respiratory support: the ESSENTIAL randomised, double-blind trial.

Activation of the TREM-1 pathway is associated with outcome in life threatening COVID-19. Data suggest that modulation of this pathway with nangibotide, a TREM-1 modulator may improve survival in TREM-1 activated patients (identified using the biomarker sTREM-1). Phase 2 double-blind randomized controlled trial assessing efficacy, safety, and optimum treatment population of nangibotide (1.0mg/kg/h) compared to placebo. Patients aged 18-75 years were eligible within 7 days of SARS-CoV-2 documentation and within 48h of the onset of invasive or non-invasive respiratory support because of COVID-19-related ARDS. Patients were included from September 2020 to April 2022, with a pause in recruitment between January and August 2021. Primary outcome was the improvement in clinical status defined by a seven-point ordinal scale in the overall population with a planned sensitivity analysis in the subgroup of patients with a sTREM-1 level above the median value at baseline (high sTREM-1 group). Secondary endpoints included safety and all-cause 28-day and day 60 mortality. The study was registered in EudraCT (2020-001504-42) and ClinicalTrials.gov (NCT04429334). The study was stopped after 220 patients had been recruited. Of them, 219 were included in the mITT analysis. Nangibotide therapy was associated with an improved clinical status at day 28. Fifty-two (52.0%) of patients had improved in the placebo group compared to 77 (64.7%) of the nangibotide treated population, an odds ratio (95% CI) for improvement of 1.79 (1.02-3.14), p=0.043. In the high sTREM-1 population, 18 (32.7%) of placebo patients had improved by day 28 compared to 26 (48.1%) of treated patients, an odds ratio (95% CI) of 2.17 (0.96-4.90), p=0.063 was observed. In the overall population, 28 (28.0%) of placebo treated patients were not alive at the day 28 visit compared to 19 (16.0%) of nangibotide treated patients, an absolute improvement (95% CI) in all-cause mortality at day 28, adjusted for baseline clinical status of 12.1% (1.18-23.05). In the high sTREM-1 population (n=109), 23 (41.8%) of patients in the placebo group and 12 (22.2%) of patients in the nangibotide group were not alive at day 28, an adjusted absolute reduction in mortality of 19.9% (2.78-36.98). The rate of treatment emergent adverse events was similar in both placebo and nangibotide treated patients. Whilst the study was stopped early due to low recruitment rate, the ESSENTIAL study demonstrated that TREM-1 modulation with nangibotide is safe in COVID-19, and results in a consistent pattern of improved clinical status and mortality compared to placebo. The relationship between sTREM-1 and both risk of death and treatment response merits further evaluation of nangibotide using precision medicine approaches in life threatening viral pneumonitis. The study was sponsored by Inotrem SA.

Assessment of Hypertension Complications and Health Service Use 5 Years After Implementation of a Multicomponent Intervention

There is a lack of information regarding the impact of implementing a protocol-driven, team-based, multicomponent intervention in public primary care settings on hypertension-related complications and health care burden over the long term. To compare hypertension-related complications and health service use at 5 years among patients managed with Risk Assessment and Management Program for Hypertension (RAMP-HT) vs usual care. In this population-based prospective matched cohort study, patients were followed up until the date of all-cause mortality, an outcome event, or last follow-up appointment before October 2017, whichever occurred first. Participants included 212 707 adults with uncomplicated hypertension managed at 73 public general outpatient clinics in Hong Kong between 2011 and 2013. RAMP-HT participants were matched to patients receiving usual care using propensity score fine stratification weightings. Statistical analysis was conducted from January 2019 to March 2023. Nurse-led risk assessment linked to electronic action reminder system, nurse intervention, and specialist consultation (as necessary), in addition to usual care. Hypertension-related complications (cardiovascular diseases, end-stage kidney disease), all-cause mortality, public health service use (overnight hospitalization, attendances at accident and emergency department, specialist outpatient clinic, and general outpatient clinic). A total of 108 045 RAMP-HT participants (mean [SD] age: 66.3 [12.3] years; 62 277 [57.6%] female) and 104 662 patients receiving usual care (mean [SD] age 66.3 [13.5] years; 60 497 [57.8%] female) were included. After a median (IQR) follow-up of 5.4 (4.5-5.8) years, RAMP-HT participants had 8.0% absolute risk reduction in cardiovascular diseases, 1.6% absolute risk reduction in end-stage kidney disease, and 10.0% absolute risk reduction in all-cause mortality. After adjusting for baseline covariates, the RAMP-HT group was associated with lower risk of cardiovascular diseases (hazard ratio [HR], 0.62; 95% CI, 0.61-0.64), end-stage kidney disease (HR, 0.54; 95% CI, 0.50-0.59), and all-cause mortality (HR, 0.52; 95% CI, 0.50-0.54) compared with the usual care group. The number needed to treat to prevent 1 cardiovascular disease event, end-stage kidney disease, and all-cause mortality was 16, 106, and 17, respectively. RAMP-HT participants had lower hospital-based health service use (incidence rate ratios ranging from 0.60 to 0.87) but more general outpatient clinic attendances (IRR, 1.06; 95% CI, 1.06-1.06) compared with usual care patients. In this prospective matched cohort study involving 212 707 primary care patients with hypertension, participation in RAMP-HT was associated with statistically significant reductions in all-cause mortality, hypertension-related complications, and hospital-based health service use after 5 years.

MP-453090-7 IDENTIFYING PATIENTS WITH LVEF≤55% WHO MAY BENEFIT FROM A PRIMARY PREVENTION ICD USING SEATTLE PROPORTIONAL RISK MODEL FOR MILDLY REDUCED EF (SPRM-MR) IN 14,752 PATIENTS

Patients with EF>30-35% remain at risk of sudden cardiac death (SCD) but are not currently indicated for a primary prevention ICD. Previous research has identified greater ICD benefit in those with a higher proportion of SCD. We sought to identify patients with EF≤55% who have a high proportion of SCD who may benefit from an ICD. Patients with EF≤55% not eligible for an ICD (NYHA 1- NonIschemic EF 1-55%, Ischemic EF 31-55%, NYHA 2-4 EF 36-55%) with mode of death from clinical trials (Val-HeFT, IPreserve, HAT-AED, HEAAL, GISSI-HF) and prospective observational studies (PRE-DETERMINE, UW, and Italian HF Registry). A Cox Proportional all-cause mortality (ACM) model and logistic regression SCD proportional risk models (SPRM-MR) were derived. Patients were considered potential ICD candidates if the predicted proportion of SCD was ≥45% and the estimated sudden death rate at 5 years ≥5%. ICD benefit was estimated by applying the SPRM*ICD interaction for ACM in HFrEF patients in SCD-HeFT (https://depts.washington.edu/sprm). The cohort included 14,752 patients. During a median follow-up of 3.6±1.4 years, 2,296 (15.6%) died. SCD comprised 30.5% of known deaths. Younger age, male sex, lower EF, higher SBP, and lower creatinine were associated with a higher proportion of SCD. One in 4 patients (23%) had a predicted SCD proportion ≥45% (observed SCD proportion 53%). An estimated SCD 5-year rate of ≥5% was present in 54% of patients. The potential ICD cohort (SPRM-MR≥45% and SCD 5yr ≥5%) comprised 11% of the entire study population. This was 17% with EF ≤45% vs <1% with EF >45%. In the potential ICD cohort, the 5 year Kaplan Meier ACM was 16.8% with 52% sudden death (∼8.7% at 5 years) vs. 20.9% ACM with 28% sudden death in the remaining patients. The estimated ICD benefit was a relative risk reduction in ACM of 27% with an ∼5% absolute risk reduction in ACM at 5 years. The 5 year number needed to treat of 20. Nearly 1 in 5 patients with an LVEF ≤ 45% who do not meet contemporary guideline criteria for ICD implantation demonstrate significant absolute (≥5%/5 years) and proportional (≥45%) risks of SCD. In these patients, we estimate an ICD would provide a 27% relative risk and 5% absolute risk reduction in all-cause mortality with a number needed to treat to save one life with an ICD of 20. Future efforts should focus on the use of integrating absolute and proportional risk as inclusion criteria for evaluating ICD benefit in this substantial population.

Impact of Medicaid expansion on outcomes after abdominal aortic aneurysm repair

ObjectiveLack of insurance has been independently associated with an increased risk of in-hospital mortality after abdominal aortic aneurysm repair, possibly due to worse control of comorbidities and delays in diagnosis and treatment. Medicaid expansion has improved insurance rates and access to care, potentially benefiting these patients. We sought to assess the association between Medicaid expansion and outcomes after abdominal aortic aneurysm repair. MethodsA retrospective analysis of Healthcare Cost and Utilization Project State Inpatient Databases data from 14 states between 2012 and 2018 was conducted. The sample was restricted to first-record abdominal aortic aneurysm repairs in adults under age 65 in states that expanded Medicaid on January 1, 2014 (Medicaid expansion group) or had not expanded before December 31, 2018 (non-expansion group). The Medicaid expansion and non-expansion groups were compared between pre-expansion (2012-2013) and post-expansion (2014-2018) time periods to assess baseline demographic and operative differences. We used difference-in-differences multivariable logistic regression adjusted for patient factors, open vs endovascular repair, and standard errors clustered by state. Our primary outcome was in-hospital mortality. Outcomes were stratified by insurance type. ResultsWe examined 8995 patients undergoing abdominal aortic aneurysm repair, including 3789 (42.1%) in non-expansion states and 5206 (57.9%) in Medicaid expansion states. Rates of Medicaid insurance were unchanged in non-expansion states but increased in Medicaid expansion states post-expansion (non-expansion: 10.9% to 9.8%; P = .346; expansion: 9.7% to 19.7%; P < .001). One in 10 patients from both non-expansion and Medicaid expansion states presented with ruptured aneurysms, which did not change over time. Rates of open repair decreased in both non-expansion and Medicaid expansion states over time (non-expansion: 25.1% to 19.2%; P < .001; expansion: 25.2% to 18.4%; P < .001). On adjusted difference-in-differences analysis between expansion and non-expansion states pre-to post-expansion, Medicaid expansion was associated with a 1.02% absolute reduction in in-hospital mortality among all patients (95% confidence interval, −1.87% to −0.17%; P = .019). Additionally, among patients who were either on Medicaid or were uninsured (ie, the patients most likely to be impacted by Medicaid expansion), a larger 4.17% decrease in in-hospital mortality was observed (95% confidence interval, −6.47% to −1.87%; P < .001). In contrast, no significant difference-in-difference in mortality was observed for privately insured patients. ConclusionsMedicaid expansion was associated with decreased in-hospital mortality after abdominal aortic aneurysm repair among all patients and particularly among patients who were either on Medicaid or were uninsured. Our results provide support for improved access to care for patients undergoing abdominal aortic aneurysm repair through Medicaid expansion.

Estimated mortality with early empirical antibiotic coverage of methicillin-resistant Staphylococcus aureus in hospitalized patients with bacterial infections: a systematic review and meta-analysis.

We performed a systematic review and meta-analysis to estimate the effect of early active empirical antibiotics for MRSA on mortality, both in patients admitted with MRSA infections and in patients admitted with common infectious syndromes, for whom the causative pathogen may not have been MRSA. A systematic literature search was conducted using Embase, MEDLINE, PubMed, Web of Science, Cochrane, Scopus and Google Scholar from the earliest entry through to 26 April 2022. We included studies of patients hospitalized with culture-proven MRSA infections that compared mortality rates depending on whether patients received active empirical antibiotics. The primary outcome was the adjusted OR for mortality with early active empirical antibiotics. After performing random-effects meta-analysis, we estimated the absolute risk reduction in mortality with initial empirical MRSA coverage for common infectious syndromes based on the prevalence of MRSA and baseline mortality rate for each syndrome, as reported in the medical literature. Of an initial 2136 unique manuscripts, 37 studies (11 661 participants) met our inclusion criteria. Fifteen studies (6066 participants) reported adjusted OR of mortality. The pooled adjusted OR for mortality was 0.64 (95% CI, 0.48-0.84), favouring active empirical antibiotics. The estimated absolute mortality benefit was 0% for patients with pneumonia, 0.1% (95% CI, 0.04-0.2) for non-critically ill patients with soft tissue infections, 0.04% (95% CI, 0.01-0.05) for non-critically ill patients with urinary tract infections, 0.6% (95% CI, 0.2-1.0) for patients with septic shock, and 1.0% (95% CI, 0.3-1.4) for patients with catheter-related infections admitted to ICUs. For the three most common infections in the hospital, the absolute benefit on mortality of empirical antibiotics against MRSA is 0.1% or less. Meaningful benefit of empirical antimicrobials against MRSA is limited to patients with approximately 30% mortality and 10% prevalence of MRSA. Avoiding empirical antibiotics against MRSA for low-risk infections would substantially reduce the use of anti-MRSA therapy.