Outcomes and risk factors for mortality in clostridioides difficile infection in patients with NAFLD and NASH.

INTRODUCTION AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and can progress to non-alcoholic steatohepatitis (NASH) and, ultimately, cirrhosis. Clostridioides difficile is the most common nosocomial cause of diarrhea and is associated with worse clinical outcomes in other liver diseases, including cirrhosis, but has not been extensively evaluated in concomitant NAFLD/NASH. MATERIALS AND METHODS: We conducted a retrospective cohort study using the National Inpatient Sample database from 2015 to 2017. Patients with a diagnosis of CDI, NAFLD, and NASH were identified using International Classification of Diseases (Tenth Revision) codes. The outcomes of our study include length of stay, hospitalization cost, mortality, and predictors of mortality. RESULTS: The CDI and NASH cohort had a higher degree of comorbidity burden and prevalence of peptic ulcer disease, congestive heart failure, diabetes mellitus, and cirrhosis. Patients with NASH and CDI had a significantly higher mortality rate compared to the CDI only cohort (mortality, 7.11 % vs. 6.36 %; P = 0.042). Patients with CDI and NASH were at increased risk for liver-related complications, acute kidney injury, and septic shock (P < 0.001) compared to patients with CDI only. Older age, intestinal complications, pneumonia, sepsis and septic shock, and liver failure conferred an increased risk of mortality among the CDI and NASH cohort. CONCLUSIONS: Patients with NASH had a higher rate of liver-related complications, progression to septic shock, and mortality rate following CDI infection compared to the CDI only cohort.

Health Care Resource Utilization and Costs for Patients with Spinal Muscular Atrophy: Findings from a Retrospective US Claims Database Analysis.

INTRODUCTION: Spinal muscular atrophy (SMA) is a neurogenic disorder associated with progressive loss of muscle function, respiratory failure, and premature mortality. This study aimed to describe and compare real-world health care resource utilization (HCRU) and costs for US patients with SMA treated with disease-modifying treatments, including onasemnogene abeparvovec, nusinersen, and/or risdiplam. METHODS: This study used claims and structured electronic medical record data from the HealthVerity claims database (January 1, 2017-March 31, 2021). Eligible patients were aged ≤ 2 years at index (treatment initiation or switch), diagnosed with SMA, had ≥ 1 pharmacy/medical claim for onasemnogene abeparvovec, nusinersen, and/or risdiplam, and continuous enrollment ≥ 1 month pre- and ≥ 2 months post-index. SMA-related HCRU and costs during the study period (> 12 months post-index) were compared between treatment groups before and after propensity score weighting. Costs were adjusted to 2021 USD. RESULTS: Of 74 included patients, 62 (83.8%) received nusinersen and 12 (16.2%) received onasemnogene abeparvovec (monotherapy, n = 9; onasemnogene abeparvovec after nusinersen [switching], n = 3). After weighting, nusinersen-treated patients had greater annual numbers of inpatient (mean 5.3 nusinersen vs. 1.8 onasemnogene abeparvovec) and emergency department (mean 3.0 nusinersen vs. 1.5 onasemnogene abeparvovec; p < 0.05) visits, and greater annual SMA-related medical costs (mean $78,446 nusinersen vs. $29,438 onasemnogene abeparvovec; mean difference $49,007, p < 0.05) than onasemnogene abeparvovec-treated patients. Onasemnogene abeparvovec-treated patients incurred greater SMA-treatment pharmacy costs than nusinersen-treated patients (mean $2,241,875 onasemnogene abeparvovec vs. $693,191 nusinersen; mean difference $1,548,684, p < 0.05). CONCLUSIONS: SMA is associated with substantial economic burden. Patients treated with onasemnogene abeparvovec had greater SMA treatment-related pharmacy costs but lower SMA-related HCRU and medical costs compared with patients receiving nusinersen monotherapy.

Spinal muscular atrophy (SMA) is a crippling neurodegenerative disease with symptoms of respiratory failure, muscle weakness and loss of function, and premature death. This study describes and compares real-world health care resource utilization (HCRU) and costs for US patients with SMA receiving current treatments (e.g., onasemnogene abeparvovec, nusinersen, risdiplam) using claims and electronic medical record data from a US claims database. Patients included (n = 74) in the study were ≤ 2 years old at treatment initiation/switching of treatments (index), had been diagnosed with SMA and had one or more pharmacy or medical claim for onasemnogene abeparvovec, nusinersen, or risdiplam, and were continuously enrolled for ≥ 1 month before and ≥ 2 months after index. SMA-related HCRU and costs during the study period (up to 12 months post-index) were compared between treatment groups before and after propensity score weighting, with costs adjusted to 2021 USD. Propensity score weighting allows better comparison between patients in treatment and comparison groups by assigning patients different "weights." This weighting allows investigators to be certain that differences in outcomes between patient groups are a result of a particular treatment. After weighting, nusinersen-treated patients had a greater number of inpatient and emergency department visits and greater SMA-related medical costs annually, whereas patients who received onasemnogene abeparvovec had greater pharmacy costs. Our study indicates the greater medical costs among patients receiving nusinersen were largely driven by invasive procedures, such as tracheostomy and gastrostomy, that required hospitalization, but the exact mechanism of greater HCRU/costs associated with nusinersen needs to be further assessed.

Incidence of Non-variceal Upper Gastrointestinal Bleeding Worsens Outcomes with Acute Coronary Syndrome: Result of a National Cohort.

INTRODUCTION: Upper gastrointestinal bleeding (UGIB) is a feared complication of acute coronary syndrome (ACS) and has been shown to increase morbidity and mortality. Our aim was to assess the incidence of non-variceal UGIB in patients with ACS in a national cohort and its impact on in-hospital mortality, length of stay (LOS), and cost of hospitalization. METHODS: This was a retrospective cohort study analyzing the 2016 Nationwide Inpatient Sample (NIS) utilizing ICD 10 CM codes. Principal discharge diagnoses of ACS (STEMI, NSTEMI, and UA) in patients over 18 years old were included. Non-variceal UGIB with interventions including endoscopy, angiography, and embolization were also evaluated. Primary outcome was the national incidence of concomitant non-variceal UGIB in the setting of ACS. Secondary outcomes included in-hospital mortality, length of stay, and cost of stay. RESULTS: A total of 661,404 discharges with principal discharge diagnosis of ACS in 2016 were analyzed. Of the included cohort, 0.80% (n = 5324) were complicated with non-variceal UGIB with increased frequency in older patients (OR 1.03, 95% CI 1.03-1.04; p = 0.0001). Despite endoscopic evaluation, 17.35% (n = 744) underwent angiography. After adjustment of confounders, inpatient mortality was significantly higher in patients with UGIB (OR 2.07, 95% CI 1.63-2.63, p = 0.0001). Non-variceal UGIB also led to significantly longer LOS (10.38 days vs 4.37 days, p = 0.0001) and cost of stay ($177,324 vs $88,468, p = 0.0001). DISCUSSION: Our study shows that the national incidence of non-variceal UGIB complicating ACS is low at less than 1%, but resulted in significantly higher inpatient mortality, LOS, and hospitalization charges.

Association of Clostridioides difficile with adverse clinical outcomes in patients with acute diverticulitis: A nationwide study.

BACKGROUND AND AIM: Acute diverticulitis (AD) is a common gastrointestinal disease with a significant health care-associated burden. Patients hospitalized with AD have many risk factors for developing Clostridioides difficile infection (CDI). CDI is associated with poor outcomes in many diseases but has yet to be studied in AD. METHODS: We utilized data from the National Inpatient Sample from January 2012 to October 2015 for patients hospitalized with AD and CDI compared with AD alone. Primary outcomes, which were mortality, length of stay, and hospitalization cost, were compared. Secondary outcomes were complications of diverticulitis and need for surgical interventions. Risk factors for mortality in AD and risk factors associated with CDI in AD patients were analyzed. RESULTS: Among 767 850 hospitalizations for AD, 8755 also had CDI. A propensity score-matched cohort analysis demonstrated that CDI was associated with increased risk of inpatient mortality (odds ratio [OR] 2.78, 95% confidence interval [CI] 1.30, 5.95), prolonged duration of hospitalization by 4.27 days (P < 0.0001), total hospital cost by $33 271 (P < 0.0001), need for surgery (OR 1.45, 95% CI 1.22, 1.71), and complications of diverticulitis (OR 1.45, 95% CI 1.21, 1.74). Predictors of CDI among patients with AD included female gender (1.12 OR, 95% CI 1.01, 1.24), three or more comorbidities (1.81 OR, 95% CI 1.57, 2.09), and admissions to teaching hospitals (1.44 OR, 95% CI 1.22, 1.70). CONCLUSIONS: Clostridioides difficile infection in AD is associated with increased mortality, length of stay, and hospital cost. Preventative measures should be made for at-risk patients with AD to decrease infection rate and poor outcomes.

Designing Policy Solutions to Build a Healthier Rural America.

Disparities exist in the health, livelihood, and opportunities for the 46-60 million people living in America's rural communities. Rural communities across the United States need a new energy and focus concentrated around health and health care that allows for the designing capturing, and spreading of existing and new innovations. This paper aims to provide a framework for policy solutions to build a healthier rural America describing both the current state of rural health policy and the policies and practices in states that could be used as a national model for positive change.

Development of Entrustable Professional Activities for Advanced Inflammatory Bowel Disease Fellowship Training in the United States.

BACKGROUND: The level of inflammatory bowel disease (IBD) training in general gastroenterology fellowship is often insufficient to prepare trainees to deliver advanced IBD care in practice. Advanced IBD fellowships have been developed to fill this training gap, but there is no established curriculum, and significant variability exists across programs. Entrustable professional activities (EPAs) are practical and realistic objectives that define essential tasks of a specialty that physicians should master to be competent during independent practice. The American College of Gastroenterology (ACG) and Crohn's & Colitis Foundation (Foundation) established a task force to develop and appraise EPAs for advanced IBD fellowship. METHODS: Entrustable professional activities were developed using a multistep approach in a similar manner to other specialties. Initial EPAs identified via focus groups were evaluated, critiqued, and changed using an iterative model of feedback. The final EPAs were selected after the task force conducted a 3-phase modified Delphi method consisting of 2 sequential rounds of web-based voting and an in-person consensus meeting. RESULTS: Ten EPAs for advanced IBD fellowship were established including detailed descriptions with the associated knowledge, skills, and attitudes for each that can serve as curricular milestones. CONCLUSION: Ten EPAs describing the core work of an advanced IBD fellowship-trained physician have been established by a multisociety task force. Creating EPAs for an advanced curriculum comes with unique challenges, particularly the need to prevent duplication of prior training competencies while demonstrating the potential for unique milestones.

Portal Hypertension and Chronic Kidney Disease Significantly Increase the Risk of Early Unplanned Readmissions in GAVE- Related Admissions.

BACKGROUND AND AIMS: Gastric antral vascular ectasia (GAVE) is an uncommon cause of non-variceal upper gastrointestinal bleeding that is characterized by dilation of blood vessels in the antrum of the stomach. Various co-morbidities are associated with the development of GAVE, but the impact of co-morbidities on unplanned GAVE readmissions is unclear. The aim of this study was to assess the national incidence, 30-day mortality rate, and 30-day readmissions related to GAVE. Secondary outcomes were evaluation of predictors of early readmission, hospital length of stay (LOS) and total hospitalization charges. METHODS: Using the 2016 National Readmission Database, we analyzed discharges for GAVE. ICD-10 CM codes were utilized to identify associated comorbidities and inpatient procedures during the index admission. 30-day readmissions were identified for GAVE. Secondary measures of outcomes including LOS and hospitalization charges were also calculated. Risk factors for early readmission were also evaluated using multivariate analysis to adjust for confounders. RESULTS: A total of 18,375 index admissions for GAVE were identified. 20.49% (n=3,720) of the discharged patients were readmitted within 30 days. 30-day mortality of GAVE-related admissions was 1.82% (n=335). Early readmissions accounted for 20,157 hospital days along with $189 million in hospitalization costs. Multivariate analysis revealed that the presence of portal hypertension (OR 1.63; 95% CI 1.37-1.93; p=0.0001) and chronic kidney disease (CKD) (OR 1.62, 95% CI 1.44-1.82; p<0.0001) significantly increased the odds of early readmission. CONCLUSIONS: Our analysis demonstrates that the overall 30-day mortality rate of GAVE-related admissions is relatively low, but the 30-day readmission rate is significantly high. Patients with comorbid CKD and portal hypertension have a significantly higher risk of readmission. Further studies are required to determine if therapeutic interventions such as argon plasma coagulation or radiofrequency ablation during the index admission may prevent readmissions in these specific subgroups.

Value-based care for the treatment and evaluation of benign prostatic hyperplasia: an analysis of a metropolitan service area claims database.

PURPOSE: With an aging population, cost containment and improved outcomes will be crucial for a sustainable healthcare ecosystem. Current data demonstrate great variation in payments for procedures and diagnostic workup of benign prostatic hyperplasia (BPH). To help determine the best financial value in BPH care, we sought to analyze the major drivers of total payments in BPH. MATERIALS AND METHODS: Commercial and Medicare claims from the Truven Health Analytics Markestscan® database for the Austin, Texas Metropolitan Service Area from 2012 to 2014 were queried for encounters with diagnosis and procedural codes related to BPH. Linear regression was utilized to assess factors related to BPH-related payments. Payments were then compared between surgical patients and patients managed with medication alone. RESULTS: Major drivers of total payments in BPH care were operative, namely transurethral resection of prostate (TURP) [$2778, 95% CI ($2385-$3171), p < 0.001) and photoselective vaporization (PVP) ($3315, 95% CI ($2781-$3849) p < 0.001). Most office procedures were also associated with significantly higher payments, including cystoscopy [$708, 95% CI ($417-$999), p < 0.001], uroflometry [$446, 95% CI ($225-668), p < 0.001], urinalysis [$167, 95% CI ($32-$302), p = 0.02], postvoid residual (PVR) [$245, 95% CI ($83-$407), p < 0.001], and urodynamics [$1251, 95% CI ($405-2097), p < 0.001]. Patients who had surgery had lower payments for their medications compared to patients who had no surgery [$120 (IQR: $0, $550) vs. $532 (IQR: $231, $1852), respectively, p < 0.001]. CONCLUSION: Surgery and office-based procedures are associated with increased payments for BPH treatment. Although payments for surgery were more in total, surgical patients paid significantly less for BPH medications.

Blunt versus penetrating trauma: Is there a resource intensity discrepancy?

BACKGROUND: The rising cost of healthcare requires responsible allocation of resources. Not all trauma centers see the same types of patients. We hypothesized that patients with blunt injuries require more resources than patients with penetrating injuries. METHODS: This was a retrospective analysis of all highest-level activation trauma patients at our busy urban Level I Trauma Center over five years. Data included demographics, injuries, hospital charges, and resources used. A p value < 0.05 was significant. RESULTS: 4578 patients were included (2037 blunt and 2541 penetrating). Blunt patients were more severely injured, more often admitted, required more radiographic studies, had longer hospital, intensive care unit, and mechanical ventilation days, and therefore, higher hospital charges. CONCLUSIONS: Within one center, patients with blunt injuries required more resources than those with penetrating injuries. Understanding this pattern will allow trauma systems to better allocate limited resources based on each center's mechanism of injury distribution.

Pricing of monoclonal antibody therapies: higher if used for cancer?

OBJECTIVES: The rising prices of specialty drugs have prompted a debate about how medications are priced. With the average price of cancer drugs doubling in the last decade, the unsustainability of drug prices is especially concerning in oncology and hematology. The objective of this study was to compare the prices of monoclonal antibodies (mAbs) approved in the last 20 years by the FDA across disease states. STUDY DESIGN: We identified all indications approved by the FDA for mAbs from 1997 to 2016 and calculated the annual price of 1-year treatment for each mAb-indication combination as the product of the US average wholesale price per milligram and the recommended dose. METHODS: We compared the annual price of treatment with each mAb across disease states using generalized linear models with gamma distribution and log link, controlling for route of administration, chemical structure, source, and time since FDA approval. RESULTS: The average annual price of a mAb was $96,731, exceeding $100,000 for 34 mAb-indication combinations. Oncology and hematology mAbs represented 40% of the mAb-indication combinations approved, yet they accounted for more than 85% of those priced $100,000 or higher. After adjusting for factors that can affect production costs, the annual price of oncology or hematology mAbs was $149,622 higher than those used in cardiovascular or metabolic disorders; $98,981 higher than in immunology; $128,856 higher than in infectious diseases or allergy; and $106,830 higher than in ophthalmology (all P <.001). CONCLUSIONS: The annual price of mAb therapies is about $100,000 higher in oncology and hematology than in other disease states.

Mini-Mental State Examination (MMSE) for the detection of dementia in clinically unevaluated people aged 65 and over in community and primary care populations.

BACKGROUND: The Mini Mental State Examination (MMSE) is a cognitive test that is commonly used as part of the evaluation for possible dementia. OBJECTIVES: To determine the diagnostic accuracy of the Mini-Mental State Examination (MMSE) at various cut points for dementia in people aged 65 years and over in community and primary care settings who had not undergone prior testing for dementia. SEARCH METHODS: We searched the specialised register of the Cochrane Dementia and Cognitive Improvement Group, MEDLINE (OvidSP), EMBASE (OvidSP), PsycINFO (OvidSP), LILACS (BIREME), ALOIS, BIOSIS previews (Thomson Reuters Web of Science), and Web of Science Core Collection, including the Science Citation Index and the Conference Proceedings Citation Index (Thomson Reuters Web of Science). We also searched specialised sources of diagnostic test accuracy studies and reviews: MEDION (Universities of Maastricht and Leuven, www.mediondatabase.nl), DARE (Database of Abstracts of Reviews of Effects, via the Cochrane Library), HTA Database (Health Technology Assessment Database, via the Cochrane Library), and ARIF (University of Birmingham, UK, www.arif.bham.ac.uk). We attempted to locate possibly relevant but unpublished data by contacting researchers in this field. We first performed the searches in November 2012 and then fully updated them in May 2014. We did not apply any language or date restrictions to the electronic searches, and we did not use any methodological filters as a method to restrict the search overall. SELECTION CRITERIA: We included studies that compared the 11-item (maximum score 30) MMSE test (at any cut point) in people who had not undergone prior testing versus a commonly accepted clinical reference standard for all-cause dementia and subtypes (Alzheimer disease dementia, Lewy body dementia, vascular dementia, frontotemporal dementia). Clinical diagnosis included all-cause (unspecified) dementia, as defined by any version of the Diagnostic and Statistical Manual of Mental Disorders (DSM); International Classification of Diseases (ICD) and the Clinical Dementia Rating. DATA COLLECTION AND ANALYSIS: At least three authors screened all citations.Two authors handled data extraction and quality assessment. We performed meta-analysis using the hierarchical summary receiver-operator curves (HSROC) method and the bivariate method. MAIN RESULTS: We retrieved 24,310 citations after removal of duplicates. We reviewed the full text of 317 full-text articles and finally included 70 records, referring to 48 studies, in our synthesis. We were able to perform meta-analysis on 28 studies in the community setting (44 articles) and on 6 studies in primary care (8 articles), but we could not extract usable 2 x 2 data for the remaining 14 community studies, which we did not include in the meta-analysis. All of the studies in the community were in asymptomatic people, whereas two of the six studies in primary care were conducted in people who had symptoms of possible dementia. We judged two studies to be at high risk of bias in the patient selection domain, three studies to be at high risk of bias in the index test domain and nine studies to be at high risk of bias regarding flow and timing. We assessed most studies as being applicable to the review question though we had concerns about selection of participants in six studies and target condition in one study.The accuracy of the MMSE for diagnosing dementia was reported at 18 cut points in the community (MMSE score 10, 14-30 inclusive) and 10 cut points in primary care (MMSE score 17-26 inclusive). The total number of participants in studies included in the meta-analyses ranged from 37 to 2727, median 314 (interquartile range (IQR) 160 to 647). In the community, the pooled accuracy at a cut point of 24 (15 studies) was sensitivity 0.85 (95% confidence interval (CI) 0.74 to 0.92), specificity 0.90 (95% CI 0.82 to 0.95); at a cut point of 25 (10 studies), sensitivity 0.87 (95% CI 0.78 to 0.93), specificity 0.82 (95% CI 0.65 to 0.92); and in seven studies that adjusted accuracy estimates for level of education, sensitivity 0.97 (95% CI 0.83 to 1.00), specificity 0.70 (95% CI 0.50 to 0.85). There was insufficient data to evaluate the accuracy of the MMSE for diagnosing dementia subtypes.We could not estimate summary diagnostic accuracy in primary care due to insufficient data. AUTHORS' CONCLUSIONS: The MMSE contributes to a diagnosis of dementia in low prevalence settings, but should not be used in isolation to confirm or exclude disease. We recommend that future work evaluates the diagnostic accuracy of tests in the context of the diagnostic pathway experienced by the patient and that investigators report how undergoing the MMSE changes patient-relevant outcomes.