Medical Therapy Before, During and After Hospitalization in Medicare Beneficiaries With Heart Failure and Diabetes: Get With The Guidelines - Heart Failure Registry.

BACKGROUND: Patients hospitalized with heart failure (HF) and diabetes mellitus (DM) are at risk for worsening clinical status. Little is known about the frequency of therapeutic changes during hospitalization. We characterized the use of medical therapies before, during and after hospitalization in patients with HF and DM. METHODS: We identified Medicare beneficiaries in Get With The Guidelines-Heart Failure (GWTG-HF) hospitalized between July 2014 and September 2019 with Part D prescription coverage. We evaluated trends in the use of 7 classes of antihyperglycemic therapies (metformin, sulfonylureas, GLP-1RA, SGLT2-inhibitors, DPP-4 inhibitors, thiazolidinediones, and insulins) and 4 classes of HF therapies (evidence-based ß-blockers, ACEi or ARB, MRA, and ARNI). Medication fills were assessed at 6 and 3 months before hospitalization, at hospital discharge and at 3 months post-discharge. RESULTS: Among 35,165 Medicare beneficiaries, the median age was 77 years, 54% were women, and 76% were white; 11,660 (33%) had HFrEF (LVEF ≤ 40%), 3700 (11%) had HFmrEF (LVEF 41%-49%), and 19,805 (56%) had HFpEF (LVEF ≥ 50%). Overall, insulin was the most commonly prescribed antihyperglycemic after HF hospitalization (n = 12,919, 37%), followed by metformin (n = 7460, 21%) and sulfonylureas (n = 7030, 20%). GLP-1RA (n = 700, 2.0%) and SGLT2i (n = 287, 1.0%) use was low and did not improve over time. In patients with HFrEF, evidence-based beta-blocker, RASi, MRA, and ARNI fills during the 6 months preceding HF hospitalization were 63%, 62%, 19%, and 4%, respectively. Fills initially declined prior to hospitalization, but then rose from 3 months before hospitalization to discharge (beta-blocker: 56%-82%; RASi: 51%-57%, MRA: 15%-28%, ARNI: 3%-6%, triple therapy: 8%-20%; P < 0.01 for all). Prescription rates 3 months after hospitalization were similar to those at hospital discharge. CONCLUSIONS: In-hospital optimization of medical therapy in patients with HF and DM is common in participating hospitals of a large US quality improvement registry.

Electronic health record alerts for management of heart failure with reduced ejection fraction in hospitalized patients: the PROMPT-AHF trial.

BACKGROUND AND AIMS: Patients hospitalized for acute heart failure (AHF) continue to be discharged on an inadequate number of guideline-directed medical therapies (GDMT) despite evidence that inpatient initiation is beneficial. This study aimed to examine whether a tailored electronic health record (EHR) alert increased rates of GDMT prescription at discharge in eligible patients hospitalized for AHF. METHODS: Pragmatic trial of messaging to providers about treatment of acute heart failure (PROMPT-AHF) was a pragmatic, multicenter, EHR-based, and randomized clinical trial. Patients were automatically enrolled 48 h after admission if they met pre-specified criteria for an AHF hospitalization. Providers of patients in the intervention arm received an alert during order entry with relevant patient characteristics along with individualized GDMT recommendations with links to an order set. The primary outcome was an increase in the number of GDMT prescriptions at discharge. RESULTS: Thousand and twelve patients were enrolled between May 2021 and November 2022. The median age was 74 years; 26% were female, and 24% were Black. At the time of the alert, 85% of patients were on ß-blockers, 55% on angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, 20% on mineralocorticoid receptor antagonist (MRA) and 17% on sodium-glucose cotransporter 2 inhibitor. The primary outcome occurred in 34% of both the alert and no alert groups [adjusted risk ratio (RR): 0.95 (0.81, 1.12), P = .99]. Patients randomized to the alert arm were more likely to have an increase in MRA [adjusted RR: 1.54 (1.10, 2.16), P = .01]. At the time of discharge, 11.2% of patients were on all four pillars of GDMT. CONCLUSIONS: A real-time, targeted, and tailored EHR-based alert system for AHF did not lead to a higher number of overall GDMT prescriptions at discharge. Further refinement and improvement of such alerts and changes to clinician incentives are needed to overcome barriers to the implementation of GDMT during hospitalizations for AHF. GDMT remains suboptimal in this setting, with only one in nine patients being discharged on a comprehensive evidence-based regimen for heart failure.

Dapagliflozin vs. metolazone in heart failure resistant to loop diuretics.

BACKGROUND AND AIMS: To examine the decongestive effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin compared to the thiazide-like diuretic metolazone in patients hospitalized for heart failure and resistant to treatment with intravenous furosemide. METHODS AND RESULTS: A multi-centre, open-label, randomized, and active-comparator trial. Patients were randomized to dapagliflozin 10 mg once daily or metolazone 5-10 mg once daily for a 3-day treatment period, with follow-up for primary and secondary endpoints until day 5 (96 h). The primary endpoint was a diuretic effect, assessed by change in weight (kg). Secondary endpoints included a change in pulmonary congestion (lung ultrasound), loop diuretic efficiency (weight change per 40 mg of furosemide), and a volume assessment score. 61 patients were randomized. The mean (±standard deviation) cumulative dose of furosemide at 96 h was 977 (±492) mg in the dapagliflozin group and 704 (±428) mg in patients assigned to metolazone. The mean (±standard deviation) decrease in weight at 96 h was 3.0 (2.5) kg with dapagliflozin compared to 3.6 (2.0) kg with metolazone [mean difference 0.65, 95% confidence interval (CI) -0.12,1.41 kg; P = 0.11]. Loop diuretic efficiency was less with dapagliflozin than with metolazone [mean 0.15 (0.12) vs. 0.25 (0.19); difference -0.08, 95% CI -0.17,0.01 kg; P = 0.10]. Changes in pulmonary congestion and volume assessment score were similar between treatments. Decreases in plasma sodium and potassium and increases in urea and creatinine were smaller with dapagliflozin than with metolazone. Serious adverse events were similar between treatments. CONCLUSION: In patients with heart failure and loop diuretic resistance, dapagliflozin was not more effective at relieving congestion than metolazone. Patients assigned to dapagliflozin received a larger cumulative dose of furosemide but experienced less biochemical upset than those assigned to metolazone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04860011.

Pragmatic trial of messaging to providers about treatment of acute heart failure: The PROMPT-AHF trial.

Acute Heart failure (AHF) is among the most frequent causes of hospitalization in the United States, contributing to substantial health care costs, morbidity, and mortality. Inpatient initiation of guideline-directed medical therapy (GDMT) is recommended for patients with heart failure with reduced ejection fraction (HFrEF) to reduce the risk of cardiovascular death or HF hospitalization. However, underutilization of GDMT prior to discharge is pervasive, representing a valuable missed opportunity to optimize evidence-based care. The PRagmatic Trial Of Messaging to Providers about Treatment of Acute Heart Failure tests the effectiveness of an electronic health record embedded clinical decision support system that informs providers during hospital management about indicated but not yet prescribed GDMT for eligible AHF patients with HFrEF. PRagmatic Trial Of Messaging to Providers about Treatment of Acute Heart Failureis an open-label, multicenter, pragmatic randomized controlled trial of 1,012 patients hospitalized with HFrEF. Eligible patients randomized to the intervention group are exposed to a tailored best practice advisory embedded within the electronic health record that alerts providers to prescribe omitted GDMT. The primary outcome is an increase in the proportion of additional GDMT medication classes prescribed at the time of discharge compared to those in the usual care arm.

Rationale and design of a cluster-randomized pragmatic trial aimed at improving use of guideline directed medical therapy in outpatients with heart failure: PRagmatic trial of messaging to providers about treatment of heart failure (PROMPT-HF).

Heart failure with reduced ejection fraction (HFrEF) is one of the most common chronic illnesses in the United States and carries significant risk of morbidity and mortality. Use of guideline-directed medical therapy (GDMT) for patients with HFrEF has been shown to dramatically improve outcomes, but adoption of these treatments remains generally low. Possible explanations for poor GDMT uptake include lack of knowledge about recommended management strategies and provider reluctance due to uncertainties regarding application of said guidelines to real-world practice. One way to overcome these barriers is by harnessing the electronic health record (EHR) to create patient-centered "best practice alerts" (BPAs) that can guide clinicians to prescribe appropriate medical therapies. If found to be effective, these low-cost interventions can be rapidly applied across large integrated healthcare systems. The PRagmatic Trial Of Messaging to Providers about Treatment of Heart Failure (PROMPT-HF) trial is a pragmatic, cluster randomized controlled trial designed to test the hypothesis that tailored and timely alerting of recommended GDMT in heart failure (HF) will result in greater adherence to guidelines when compared with usual care. PROMPT-HF has completed enrollment of 1,310 ambulatory patients with HFrEF cared for by 100 providers who were randomized to receive a BPA vs usual care. The BPA alerted providers to GDMT recommended for their patients and displayed current left ventricular ejection fraction (LVEF) along with the most recent blood pressure, heart rate, serum potassium and creatinine levels, and estimated glomerular filtration rate. It also linked to an order set customized to the patient that suggests medications within each GDMT class not already prescribed. Our goal is to examine whether tailored EHR-based alerting for outpatients with HFrEF will lead to higher rates of GDMT at 30 days post randomization when compared with usual care. Additionally, we are assessing clinical outcomes such as hospital readmissions and death between the alert versus usual care group. Trial Registration: Clinicaltrials.gov NCT04514458.

Projected Clinical Benefits of Implementation of SGLT-2 Inhibitors Among Medicare Beneficiaries Hospitalized for Heart Failure.

BACKGROUND: The sodium-glucose cotransporter-2 (SGLT-2) inhibitors form the latest pillar in the management of heart failure with reduced ejection fraction (HFrEF) and appear to be effective across a range of patient profiles. There is increasing interest in initiating SGLT-2 inhibitors during hospitalization, yet little is known about the putative benefits of this implementation strategy. METHODS: We evaluated Medicare beneficiaries with HFrEF (≤ 40%) hospitalized at 228 sites in the Get With The Guidelines-Heart Failure (GWTG-HF) registry in 2016 who had linked claims data for ≥ 1 year postdischarge. We identified those eligible for dapagliflozin under the latest U.S. Food and Drug Administration label (excluding estimated glomerular filtration rates < 25 mL/min per 1.73 m2, dialysis and type 1 diabetes). We evaluated 1-year outcomes overall and among key subgroups (age ≥ 75 years, gender, race, hospital region, kidney function, diabetes status, triple therapy). We then projected the potential benefits of implementation of dapagliflozin based on the risk reductions observed in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial. RESULTS: Among 7523 patients hospitalized for HFrEF, 6576 (87%) would be candidates for dapagliflozin (mean age 79 ± 8 years, 39% women, 11% Black). Among eligible candidates, discharge use of ß-blockers, ACEi/ARB, MRA, ARNI, and triple therapy (ACEi/ARB/ARNI+ß-blocker+MRA) was recorded in 88%, 64%, 29%, 3%, and 20%, respectively. Among treatment-eligible patients, the 1-year incidence (95% CI) of mortality was 37% (36-38%) and of HF readmission was 33% (32-34%), and each exceeded 25% across all key subgroups. Among 1333 beneficiaries eligible for dapagliflozin who were already on triple therapy, the 1-year incidence of mortality was 26% (24%-29%) and the 1-year readmission due to HF was 30% (27%-32%). Applying the relative risk reductions observed in DAPA-HF, absolute risk reductions with complete implementation of dapagliflozin among treatment-eligible Medicare beneficiaries are projected to be 5% (1%-9%) for mortality and 9% (5%-12%) for HF readmission by 1 year. The projected number of Medicare beneficiaries who would need to be treated for 1 year to prevent 1 death is 19 (11-114), and 12 (8-21) would need to be treated to prevent 1 readmission due to HF. CONCLUSIONS: Medicare beneficiaries with HFrEF who are eligible for dapagliflozin after hospitalization due to HF, including those well-treated with other disease-modifying therapies, face high risks of mortality and HF readmission by 1 year. If the benefits of reductions in death and hospitalizations due to HF observed in clinical trials can be fully realized, the absolute benefits of implementation of SGLT-2 inhibitors among treatment-eligible candidates are anticipated to be substantial in this high-risk postdischarge setting.

Ribonucleoprotein Capture by in Vivo Expression of a Designer Pentatricopeptide Repeat Protein in Arabidopsis.

Pentatricopeptide repeat (PPR) proteins bind RNA via a mechanism that facilitates the customization of sequence specificity. However, natural PPR proteins have irregular features that limit the degree to which their specificity can be predicted and customized. We demonstrate here that artificial PPR proteins built from consensus PPR motifs selectively bind the intended RNA in vivo, and we use this property to develop a new tool for ribonucleoprotein characterization. We show by RNA coimmunoprecipitation sequencing (RIP-seq) that artificial PPR proteins designed to bind the Arabidopsis (Arabidopsis thaliana) chloroplast psbA mRNA bind with high specificity to psbA mRNA in vivo. Analysis of coimmunoprecipitating proteins by mass spectrometry showed the psbA translational activator HCF173 and two RNA binding proteins of unknown function (CP33C and SRRP1) to be highly enriched. RIP-seq revealed that these proteins are bound primarily to psbA RNA in vivo, and precise mapping of the HCF173 and CP33C binding sites placed them in different locations on psbA mRNA. These results demonstrate that artificial PPR proteins can be tailored to bind specific endogenous RNAs in vivo, add to the toolkit for characterizing native ribonucleoproteins, and open the door to other applications that rely on the ability to target a protein to a specified RNA sequence.

Wash-Free, Digital Immunoassay in Polydisperse Droplets.

Immunoassays are important for the detection of proteins to enable disease identification and monitor treatment, but many immunoassays suffer from sensitivity limitations. The development of digital assays has enabled highly sensitive biomarker detection and quantification, but the necessary devices typically require precisely controlled volumes to reduce biases in concentration estimates from compartment size variation. These constraints have led to systems that are often expensive, cumbersome, and challenging to operate, confining many digital assays to centralized laboratories. To overcome these limitations, we have developed a simplified digital immunoassay performed in polydisperse droplets that are prepared without any specialized equipment. This polydisperse digital droplet immunoassay (ddIA) uses proximity ligation to remove the need for wash steps and simplifies the system to a single reagent addition step. Using interleukin-8 (IL-8) as an example analyte, we demonstrated the concept with samples in buffer and diluted whole blood with limits of detection of 0.793 pM and 1.54 pM, respectively. The development of a one-pot, washless assay greatly improves usability compared to traditional immunoassays or digital-based systems that rely heavily on wash steps and can be run with common and readily available laboratory equipment such as a heater and simple fluorescent microscope. We also developed a stochastic model with physically meaningful parameters that can be utilized to optimize the assay and enable quantification without standard curves, after initial characterization of the parameters. Our polydisperse ddIA assay serves as an example of sensitive, lower-cost, and simpler immunoassays suitable for both laboratory and point-of-care applications.

RNA-binding specificity landscapes of designer pentatricopeptide repeat proteins elucidate principles of PPR-RNA interactions.

Pentatricopeptide repeat (PPR) proteins are helical-repeat proteins that offer a promising scaffold for the engineering of proteins to bind specified RNAs. PPR tracts bind RNA in a modular 1-repeat, 1-nucleotide fashion. An amino acid code specifying the bound nucleotide has been elucidated. However, this code does not fully explain the sequence specificity of native PPR proteins. Furthermore, it does not address nuances such as the contribution toward binding affinity of various repeat-nucleotide pairs or the impact of mismatches between a repeat and aligning nucleotide. We used an in vitro bind-n-seq approach to describe the population of sequences bound by four artificial PPR proteins built from consensus scaffolds. The specificity of these proteins can be accounted for by canonical code-based nucleotide recognition. The results show, however, that interactions near the 3'-end of binding sites make less contribution to binding affinity than do those near the 5'-end, that proteins with 11 and 14 repeats exhibit similar affinity for their intended targets but 14-repeats are more permissive for mismatches, and that purine-binding repeats are less tolerant of transversion mismatches than are pyrimidine-binding motifs. These findings have implications for mechanisms that establish PPR-RNA interactions and for optimizing PPR design to minimize off-target interactions.

Utilization of Left Ventricular Assist Devices in Vulnerable Adults Across Medicaid Expansion.

BACKGROUND: Continuous-flow left ventricular assist device (LVAD) implantation is a payor sensitive procedure influenced by preoperative comorbidities and social factors. Whether expansion in insurance coverage will further influence device utilization is unknown. This study sought to assess the effects of Medicaid expansion on vulnerable populations (namely racial-ethnic minorities and those with low-income status) undergoing continuous-flow LVAD implantation after the enactment of the 2014 Affordable Care Act (ACA). METHODS: Data from the 2012 to Q3 2015 State Inpatient Database were used to examine a cohort of 624 nonelderly adults (aged 18-64 y) who were given a continuous-flow LVAD in three expansion states (Kentucky, New Jersey, and Maryland) and two nonexpansion states (North Carolina and Florida). The cohort excluded patients who had a heart transplant, heart-lung transplant, or noncontinuous-flow LVAD. Poisson Interrupted Time Series was used with three-way interactions and change of slope and intercept parameters at 2014 to determine the impact of the ACA expansion on utilization of continuous-flow LVAD by race and insurance strata. RESULTS: Poisson Interrupted Time Series models show that within expansion states, the population of Medicaid and uninsured patients saw an increase in the utilization of LVAD's immediately after ACA expansion, from 2.8 in Q4 2013 to 9.83 Q1 2014 (incidence rate ratio [IRR] 5.26, P = 0.02). Utilization eventually declined to pre-ACA levels, however, ending with 3.04 LVADs in Q3 2015 (IRR 0.84, 95% confidence interval 0.58-1.20). Models testing for racial effect showed no statistically preferential or disparate effects (immediate effect IRR 1.608, P = 0.506; marginal effect IRR 0.897, P = 0.512). CONCLUSIONS: These findings show that despite expanded insurance coverage, the utilization of continuous-flow LVADs was not increased in nonelderly racial and ethnic minorities following the ACA Medicaid expansion. Although these findings are preliminary and require further long-term evaluation, they suggest that insurance coverage alone does not play a significant role in increased utilization of continuous-flow LVAD. These findings point toward the importance of further exploring social, medical, and hospital drivers of these disparities.

Impact of intraoperative distractions on patient safety: a prospective descriptive study using validated instruments.

BACKGROUND: There is emerging evidence indicating that distractions in the operating room (OR) are prevalent. Studies have shown a negative impact of distractions, but they have been conducted mostly with residents in simulated environments. We tested the hypothesis that intraoperative distractions are associated with deterioration in patient safety checks in the OR. METHODS: We assessed 24 elective urologic procedures. Blinded trained assessors (two surgeons, one psychologist) used validated instruments to prospectively assess in vivo frequency and severity of distractions (related to communication, phones/pagers, equipment/provisions, OR environment, other hospital departments, or a member of the OR team) and completion of safety-related tasks (related to the patient, equipment, and communication). Descriptive and correlational analyses were conducted. RESULTS: Mean case duration was 70 min (mean intraoperative time 31 min). A mean of 4.0 communication distractions (range 0-9) and 2.48 other distractions (range 0-5) were recorded per case (distraction rate of one per 10 min). Distractions from external visitors (addressed to the entire team or the surgeon) and distractions due to lack of coordination between hospital departments were most disruptive. Regarding safety checks, patient tasks were completed most often (85-100 %) followed by equipment tasks (75-100 %) and communication tasks (55-90 %). Correlational analyses showed that more frequent/severe communication distractions were linked to lower completion of patient checks intraoperatively (median rho -0.56, p < 0.05). CONCLUSIONS: Distractions are prevalent in ORs and in this study were linked to deterioration in intraoperative patient safety checks. Surgeons should be mindful of their tolerance to distractions. Surgical leadership can help control distractions and reduce their potential impact on patient safety and performance.

Measuring Sleep Quality Among Medical Students Using the Epworth Sleepiness Scale.

Introduction While existing literature establishes the positive impact of sleep on test performance among medical students and its correlation with better outcomes among physicians, there is a notable gap in the quantitative understanding of how the transition from preclinical to clinical training affects sleep quality. Methods Our survey was sent to all medical students attending the California University of Science and Medicine between April 2023 and January 2024. The relative risks for having an Epworth sleepiness scale (ESS) greater than 10 were calculated and compared for various subgroups in our sample. Univariate logistic regression analysis was also carried out to assess the effect of covariates on our primary outcome. Results In total, our sample consisted of 124 medical students. Only 11.3% (n=14) were somewhat dissatisfied or very dissatisfied with their medical school experience. The relative risk of having an ESS > 10 when on clinical rotations was 2.06 (95% CI: 1.22-3.49). Conclusion This study demonstrates that the risk of medical students experiencing excessive sleepiness, defined by an ESS > 10, doubles when students are on clinical rotations. Despite being limited by information bias and a smaller sample size, this study provides interesting pilot data on the quantitative examination of sleepiness among medical students and may be used to guide areas for future work.

A Rare Case of Arthroscopic Lateral Segmental Meniscal Allograft Transplantation (SMALT) and Osteochondral Allograft Transplantation (OCA) of the Lateral Femoral Condyle Augmented With Bone Marrow Aspirate Concentrate (BMAC).

The meniscus of the knee serves as a crucial load-bearing structure, and its damage can significantly impact weight distribution. In addressing focal meniscal defects, segmental meniscal allograft transplantation (SMALT) emerges as an innovative solution. Here, we detail a case involving a young, active female who underwent SMALT augmented with osteochondral allograft transplantation (OCA) and bone marrow aspirate concentration (BMAC). The patient, a 40-year-old former Division I volleyball player, previously underwent arthroscopic procedures and presented with knee pain alongside complex lateral meniscus tear evident in magnetic resonance imaging (MRI) findings. Initial arthroscopy revealed multiple tears, including segmental deficiency at the posterior horn-body junction and a horizontal cleavage tear. Despite failed attempts at repair due to the meniscal gap, a second-stage lateral SMALT was performed, with the allograft soaked in the patient's BMAC, supplemented with OCA to the lateral femoral condyle. Rehabilitation protocols tailored to both SMALT and OCA were implemented. This represents the first documented instance of lateral SMALT, extending the scope of viable solutions for segmental meniscal deficiencies, and marking a significant milestone in orthopedic practice.

Management of Gallstone Pancreatitis: A Review.

Importance: Gallstone pancreatitis (GSP) is the leading cause of acute pancreatitis, accounting for approximately 50% of cases. Without appropriate and timely treatment, patients are at increased risk of disease progression and recurrence. While there is increasing consensus among guidelines for the management of mild GSP, adherence to these guidelines remains poor. In addition, there is minimal evidence to guide clinicians in the treatment of moderately severe and severe pancreatitis. Observations: The management of GSP continues to evolve and is dependent on severity of acute pancreatitis and concomitant biliary diagnoses. Across the spectrum of severity, there is evidence that goal-directed, moderate fluid resuscitation decreases the risk of fluid overload and mortality compared with aggressive resuscitation. Patients with isolated, mild GSP should undergo same-admission cholecystectomy; early cholecystectomy within 48 hours of admission has been supported by several randomized clinical trials. Cholecystectomy should be delayed for patients with severe disease; for severe and moderately severe disease, the optimal timing remains unclear. Preoperative endoscopic retrograde cholangiopancreatography (ERCP) is only useful for patients with suspected cholangitis or biliary obstruction, although the concomitance of these conditions in patients with GSP is rare. Modality of evaluation of the common bile duct to rule out concomitant choledocholithiasis varies and should be tailored to level of concern based on objective measures, such as laboratory results and imaging findings. Among these modalities, intraoperative cholangiography is associated with reduced length of stay and decreased use of ERCP. However, the benefit of routine intraoperative cholangiography remains in question. Conclusions and Relevance: Treatment of GSP is dependent on disease severity, which can be difficult to assess. A comprehensive review of clinically relevant evidence and recommendations on GSP severity grading, fluid resuscitation, timing of cholecystectomy, need for ERCP, and evaluation and management of persistent choledocholithiasis can help guide clinicians in diagnosis and management.

Necrotizing Soft Tissue Infections: A Review.

Importance: Necrotizing soft tissue infections (NSTIs) are severe life- and limb-threatening infections with high rates of morbidity and mortality. Unfortunately, there has been minimal improvement in outcomes over time. Observations: NSTIs are characterized by their heterogeneity in microbiology, risk factors, and anatomical involvement. They often present with nonspecific symptoms, leading to a high rate of delayed diagnosis. Laboratory values and imaging help increase suspicion for NSTI, though ultimately, the diagnosis is clinical. Surgical exploration is warranted when there is high suspicion for NSTI, even if the diagnosis is uncertain. Thus, it is acceptable to have a certain rate of negative exploration. Immediate empirical broad-spectrum antibiotics, further tailored based on tissue culture results, are essential and should be continued at least until surgical debridement is complete and the patient shows signs of clinical improvement. Additional research is needed to determine optimal antibiotic duration. Early surgical debridement is crucial for improved outcomes and should be performed as soon as possible, ideally within 6 hours of presentation. Subsequent debridements should be performed every 12 to 24 hours until the patient is showing signs of clinical improvement and there is no additional necrotic tissue within the wound. There are insufficient data to support the routine use of adjunct treatments such as hyperbaric oxygen therapy and intravenous immunoglobulin. However, clinicians should be aware of multiple ongoing efforts to develop more robust diagnostic and treatment strategies. Conclusions and Relevance: Given the poor outcomes associated with NSTIs, a review of clinically relevant evidence and guidelines is warranted. This review discusses diagnostic and treatment approaches to NSTI while highlighting future directions and promising developments in NSTI management.

High-risk rural surgical patients and poor access to elective colorectal cancer surgery: insight for multilevel intervention for rural America.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of death in rural America. Rural populations are large and heterogeneous, yet patient-related drivers of inequities in CRC access are understudied. This study aimed to identify vulnerable rural populations at lower odds of undergoing elective CRC surgery. METHODS: Evaluation of the Policy Map and United States Census Bureau identified factors associated with poor surgical access in the most populous states (by total rural population). To assess whether these identified factors were associated with reduced access to elective CRC surgery, the 2007 to 2020 National Inpatient Sample was used to evaluate 69,212 hospitalizations of rural patients undergoing CRC surgery. Rural was defined as counties with a population of <250,000. Multivariable logistic regression models assessed predictors of elective CRC surgery. Patient- and hospital-level factor interactions were specified a priori. RESULTS: More than 72% of hospitalizations of rural patients were elective. Multivariate regression analysis demonstrated that older age, multimorbidity, Black race, Latino-Hispanic ethnicity, Medicaid insurance, and rural hospitals predicted lower odds of elective CRC surgery. On interaction analyses, high-risk patients were less likely to undergo elective CRC surgery in urban facilities relative to rural. CONCLUSION: In this large study of rural dwellers, ethnoracial minorities, elders, and Medicaid beneficiaries had profoundly less access to elective CRC surgery, especially when care was received in urban settings. Future studies should focus on exploring actionable social drivers of health in these rural populations. Findings underscore the need for multilevel interventions to enhance rural access to equitable and quality surgical cancer care.

Clinician-to-clinician connectedness and access to gastric cancer surgery at National Cancer Institute-designated cancer centers.

BACKGROUND: For patients with gastric cancer, the pathway from primary care (PC) clinician to gastroenterologist to cancer specialist (medical oncologist or surgeons) is referral dependent. The impact of clinician connectedness on disparities in quality gastric cancer care, such as at National Cancer Institute-designated cancer centers (NCI-CC), remains underexplored. This study evaluated how clinician connectedness influences access to gastrectomy at NCI-CC. METHODS: Maryland's All-Payer Claims Database was used to evaluate 667 patients who underwent gastrectomy for cancer from 2013 to 2018. Two separate referral linkages, defined as ≥9 shared patients, were examined: (1) PC clinicians to gastroenterologists at NCI-CC and (2) gastroenterologists to cancer specialists at NCI-CC. Multiple logistic regression models determined associations between referral linkages and odds of undergoing gastrectomy at NCI-CC. RESULTS: Only 15% of gastrectomies were performed at NCI-CC. Patients of gastroenterologists with referral links to cancer specialists at NCI-CC were more likely to be <65 years, male, White, and privately insured. Every additional referral link between PC clinician and gastroenterologist at NCI-CC and between gastroenterologist and cancer specialist at NCI-CC increased the odds of gastrectomy at NCI-CC by 71% and 26%, respectively. Black patients had half the odds as White patients in receiving gastrectomy at NCI-CC; however, adjusting for covariates including clinician-to-clinician connectedness attenuated this observation. CONCLUSION: Patients of clinicians with low connectedness and Black patients are less likely to receive gastrectomy at NCI-CC. Enhancing clinician connectedness is necessary to address disparities in cancer care. These results are relevant to policy makers, clinicians, and patient advocates striving for health equity.

Cause-Specific Health Care Costs Following Hospitalization for Heart Failure and Cost Offset With SGLT2i Therapy.

BACKGROUND: Little is known regarding differences in cause-specific costs between heart failure (HF) with ejection fraction (EF) ≤40% vs >40%, and potential cost implications of sodium glucose co-transporter 2 inhibitor (SGLT2i) therapy. OBJECTIVES: This study sought to compare cause-specific health care costs following hospitalization for HF with EF ≤40% vs >40% and estimate the cost offset with implementation of SGLT2i therapy. METHODS: This study examined Medicare beneficiaries hospitalized for HF in the Get With The Guidelines-Heart Failure registry from 2016 to 2020. Mean per-patient total (excluding drug costs) and cause-specific costs from discharge through 1-year follow-up were calculated and compared between EF ≤40% vs >40%. Next, risk reductions on total all-cause and HF hospitalizations were estimated in a trial-level meta-analysis of 5 pivotal trials of SGLT2is in HF. Finally, these relative treatment effects were applied to Medicare beneficiaries eligible for SGLT2i therapy to estimate the projected cost offset with implementation of SGLT2i, excluding drug costs. RESULTS: Among 146,003 patients, 50,598 (34.7%) had EF ≤40% and 95,405 (65.3%) had EF >40%. Mean total cost through 1 year was $40,557. Total costs were similar between EF groups overall but were higher for EF ≤40% among patients surviving the 1-year follow-up period. Patients with EF >40% had higher costs caused by non-HF and noncardiovascular hospitalizations, and skilled nursing facilities (all P < 0.001). Trial-level meta-analysis of the 5 SGLT2i clinical trials estimated 11% (rate ratio: 0.89; 95% CI: 0.84-0.93; P < 0.001) and 29% (rate ratio: 0.71; 95% CI: 0.66-0.76; P < 0.001) relative reductions in rates of total all-cause and HF hospitalizations, respectively, regardless of EF. Reductions in all-cause and HF hospitalizations were projected to reduce annual costs of readmission by $2,451 to $2,668 per patient with EF ≤40% and $1,439 to $2,410 per patient with EF >40%. CONCLUSIONS: In this large cohort of older U.S. adults hospitalized for HF, cause-specific costs of care differed among patients with EF ≤40% vs >40%. SGLT2i significantly reduced the rate of HF and all-cause hospitalizations irrespective of EF in clinical trials, and implementation of SGLT2i therapy in clinical practice is projected to reduce costs by $1,439 to $2,668 per patient over the 1 year post-discharge, excluding drug costs.

Kidney Outcomes Among Medicare Beneficiaries After Hospitalization for Heart Failure.

Importance: Kidney health has received increasing focus as part of comprehensive heart failure (HF) treatment efforts. However, the occurrence of clinically relevant kidney outcomes in contemporary populations with HF has not been well studied. Objective: To examine rates of incident dialysis and acute kidney injury (AKI) among Medicare beneficiaries after HF hospitalization. Design, Setting, and Participants: This retrospective cohort study evaluated adults aged 65 years or older who were hospitalized for HF across 372 sites in the Get With The Guidelines-Heart Failure registry in the US between January 1, 2014, and December 31, 2018. Patients younger than 65 years or requiring dialysis either during or prior to hospitalization were excluded. Data were analyzed from May 4, 2021, to March 8, 2024. Main Outcomes and Measures: The primary outcome was inpatient dialysis initiation in the year after HF hospitalization and was ascertained via linkage with Medicare claims data. Other all-cause and cause-specific hospitalizations were also evaluated. The covariate-adjusted association between discharge estimated glomerular filtration rate (eGFR) and 1-year postdischarge outcomes was examined using Cox proportional hazards regression models. Results: Overall, among 85 298 patients included in the analysis (mean [SD] age, 80 [9] years; 53% women) mean (SD) left ventricular ejection fraction was 47% (16%) and mean (SD) eGFR was 53 (29) mL/min per 1.73 m2; 54 010 (63%) had an eGFR less than 60 mL/min per 1.73 m2. By 1 year after HF hospitalization, 6% had progressed to dialysis, 7% had progressed to dialysis or end-stage kidney disease, and 7% had been readmitted for AKI. Incident dialysis increased steeply with lower discharge eGFR category: compared with patients with an eGFR of 60 mL/min per 1.73 m2 or more, individuals with an eGFR of 45 to less than 60 and of less than 30 mL/min per 1.73 m2 had higher rates of dialysis readmission (45 to <60: adjusted hazard ratio [AHR], 2.16 [95% CI, 1.86-2.51]; <30: AHR, 28.46 [95% CI, 25.25-32.08]). Lower discharge eGFR (per 10 mL/min per 1.73 m2 decrease) was independently associated with a higher rate of readmission for dialysis (AHR, 2.23; 95% CI, 2.14-2.32), dialysis or end-stage kidney disease (AHR, 2.34; 95% CI, 2.24-2.44), and AKI (AHR, 1.25; 95% CI, 1.23-1.27), with similar findings for all-cause mortality, all-cause readmission, and HF readmission. Baseline left ventricular ejection fraction did not modify the covariate-adjusted association between lower discharge eGFR and kidney outcomes. Conclusions and Relevance: In this study, older adults with HF had substantial risk of kidney complications, with an estimated 6% progressing to dialysis in the year after HF hospitalization. These findings emphasize the need for health care approaches prioritizing kidney health in this high-risk population.