Mortality, healthcare resource utilization, and cost among Medicare beneficiaries with Clostridioides difficile infection with and without sepsis.

Objective: To describe mortality, healthcare resource utilization (HRU), and costs among Medicare beneficiaries with primary Clostridioides difficile infection (pCDI) or recurrent CDI (rCDI), with and without sepsis. Methods: We conducted a retrospective observational study of 100% Medicare Fee-for-Service claims from adults aged ⩾ 65 years with ⩾1 CDI episode between 1 January 2009 and 31 December 2017. Patients were continuously enrolled in Medicare Parts A/B/D 12 months before and up to 12 months after pCDI. ICD-9/10 codes defined CDI using ⩾1 inpatient claim, or ⩾1 outpatient claim plus ⩾1 claim for CDI treatment. The pCDI episode ended after 14 days without a CDI claim. rCDI episodes started within 8 weeks from the end of a previous CDI episode. ICD-9/10 codes identified all-cause sepsis over 12 month follow-up. Results: Of 497,489 CDI patients, 41.0% (N = 203,888) had sepsis; 57.7% with sepsis died versus 32.4% without sepsis. Among patients with pCDI only (N = 345,893) or ⩾1 rCDI (N = 151,596), 39.2% and 45.1% suffered sepsis, respectively. All-cause hospitalizations were frequent for all cohorts (range: 81-99%). Among patients who died, those with sepsis versus without had more-frequent intensive care unit (ICU) use (pCDI: 29% versus 15%; rCDI: 65% versus 34%), longer hospital stays (pCDI: 12 versus 10 days; rCDI: 12 versus 9 days), and higher per-patient-per-month costs (pCDI: $34,841 versus $22,753; rCDI: $42,269 versus $25,047). In both cohorts, sepsis patients who survived had higher total costs and all-cause HRU than those without sepsis. All p < 0.001 above. Conclusions: Sepsis was common among Medicare beneficiaries with CDI. CDI patients with sepsis, especially after an rCDI, experienced higher mortality, HRU, and costs compared with those without sepsis.

Mortality, Health Care Use, and Costs of Clostridioides difficile Infections in Older Adults.

OBJECTIVES: Estimate mortality, cost, and health care resource utilization for Medicare beneficiaries aged ≥65 years who suffered a primary Clostridioides difficile infection (CDI) episode only or any recurrent CDI, and understand how outcomes covary with death. DESIGN: Retrospective observational claims analysis. SETTING AND PARTICIPANTS: Patients aged ≥65 years who had an inpatient or outpatient CDI diagnosis claim to Medicare and continuous enrollment in Medicare parts A, B, and D during the 12-month pre- and post-index periods. METHODS: Using 100% Medicare Fee-for-Service claims data for 2009-2017, primary (pCDI, n = 345,893) and recurrent (rCDI: n = 151,596) CDI episodes were identified. Demographic and clinical characteristics, mortality, health care resource utilization, and costs (per patient per month) were summarized for 12 months before and up to 12 months after episode start. Regression models were estimated for hospitalization risk, hospital length of stay (LOS), and cost to adjust for comorbidities. RESULTS: CDI-associated deaths were almost 10 times higher after recurrent CDI (25.4%) than primary CDI (2.7%). Compared with survivors, decedents were older, had higher Charlson Comorbidity Index scores, and were more likely Black. Adjusting for comorbidities, during follow-up, decedents had higher hospitalization rates [pCDI: odds ratio (OR) = 1.83, P < .001; rCDI: OR = 2.58, P < .001], and recurrent CDI decedents had more intensive care unit use (OR = 2.34, P < .001) compared with survivors. Decedents also had a longer length of stay (pCDI: +3.2 days, P < .001; rCDI: +2.6 days, P < .001), and higher total cost (pCDI: +303%, P < .001; rCDI: +297%, P < .001). CONCLUSIONS AND IMPLICATIONS: CDI is an important contributing diagnosis to all-cause mortality, particularly for recurrences. Prior to death, older Medicare beneficiaries who experienced CDI received longer, more intensive, and more costly care compared with survivors. Clinicians should be particularly attentive to prevention, identification, and appropriate treatment of CDI in older adults. Better treatments to reduce primary C difficile infection and recurrences in this vulnerable population can lower both mortality and economic burden.

Burden of illness and outcomes in second-line large B-cell lymphoma treatment: real-world analysis of Medicare beneficiaries.

Aims: To characterize elderly large B-cell lymphoma patients who progress to second-line treatment to identify potential unmet treatment needs. Patients & methods: Retrospective USA cohort study, patients receiving second-line autologous stem cell transplant (SCT) preparative regimen ('ASCT-intended') versus those who did not; stratified further into those who received a stem cell transplant and those who did not. Primary outcomes were: healthcare resource utilization, costs and adverse events. Results: 1045 patients (22.0%) were included in the ASCT-intended group, 23.3% of whom received SCT (5.1% of entire second-line population). Non-SCT patients were older and had more comorbidities and generally higher rates of healthcare resource utilization and costs. Conclusion: Elderly second-line large B-cell lymphoma patients incurred substantial costs and a minority received potentially curative SCT, suggesting significant unmet need.

Lay abstract Large B-cell lymphoma (LBCL) is an aggressive form of cancer. Although chemotherapy is often initially successful, LBCL recurs in about 50% of patients. For many years, the standard of care for recurrent LBCL has been a course of strong chemotherapy followed by stem cell transplant (SCT). However, many older patients cannot tolerate or do not respond well to chemotherapy and therefore cannot proceed to SCT. In this real-world study of Medicare patients, we found that only 5.1% of patients with recurrent LBCL ever received potentially curative SCT. They also had higher healthcare costs than similar patients who did receive SCT. This shows a significant unmet need in elderly LBCL patients that may potentially be addressed with recent treatment innovations.

Sprr2f protects against renal injury by decreasing the level of reactive oxygen species in female mice.

Renal injury leads to chronic kidney disease, with which women are not only more likely to be diagnosed than men but have poorer outcomes as well. We have previously shown that expression of small proline-rich region 2f (Sprr2f), a member of the small proline-rich region (Sprr) gene family, is increased several hundredfold after renal injury using a unilateral ureteral obstruction (UUO) mouse model. To better understand the role of Sprr2f in renal injury, we generated a Sprr2f knockout (Sprr2f-KO) mouse model using CRISPR-Cas9 technology. Sprr2f-KO female mice showed greater renal damage after UUO compared with wild-type (Sprr2f-WT) animals, as evidenced by higher hydroxyproline levels and denser collagen staining, indicating a protective role of Sprr2f during renal injury. Gene expression profiling by RNA sequencing identified 162 genes whose expression levels were significantly different between day 0 and day 5 after UUO in Sprr2f-KO mice. Of the 162 genes, 121 genes were upregulated after UUO and enriched with those involved in oxidation-reduction, a phenomenon not observed in Sprr2f-WT animals, suggesting a protective role of Sprr2f in UUO through defense against oxidative damage. Consistently, bilateral ischemia-reperfusion injury resulted in higher serum blood urea nitrogen levels and higher tissue reactive oxygen species in Sprr2f-KO compared with Sprr2f-WT female mice. Moreover, cultured renal epithelial cells from Sprr2f-KO female mice showed lower viability after oxidative damage induced by menadione compared with Sprr2f-WT cells that could be rescued by supplementation with reduced glutathione, suggesting that Sprr2f induction after renal damage acts as a defense against reactive oxygen species.

An Efficient Development Paradigm for Biosimilars.

The current development paradigm for biosimilars required by regulators in highly regulated jurisdictions is derived from the development of novel drugs and is unnecessarily burdensome and inefficient. It requires the accumulation of data from analytical, nonclinical (including in vivo studies in some jurisdictions), and clinical studies (including powered efficacy studies in most cases); this paradigm is known as 'totality of evidence' (ToE) and does not admit a conclusion of biosimilarity from analytical data alone. The record of biosimilar approvals in these jurisdictions shows that no biosimilar candidate that has been found highly similar to its reference in analytical and pharmacokinetic studies has failed to be approved. We propose a new paradigm ('confirmation of sufficient likeness', CSL) that emphasizes the demonstration of analytical resemblance between the biosimilar candidate and its reference, and permits the conclusion of biosimilarity upon this basis. CSL does not entail bridging studies between reference products, in vivo nonclinical studies, or powered efficacy studies and is, therefore, substantially more efficient than ToE while maintaining equivalent scientific rigor. Such efficiency will contribute to the attractiveness as well as the sustainability of biosimilars as a therapeutic modality.

Early detection of unilateral ureteral obstruction by desorption electrospray ionization mass spectrometry.

Desorption electrospray ionization mass spectrometry (DESI-MS) is an emerging analytical tool for rapid in situ assessment of metabolomic profiles on tissue sections without tissue pretreatment or labeling. We applied DESI-MS to identify candidate metabolic biomarkers associated with kidney injury at the early stage. DESI-MS was performed on sections of kidneys from 80 mice over a time course following unilateral ureteral obstruction (UUO) and compared to sham controls. A predictive model of renal damage was constructed using the LASSO (least absolute shrinkage and selection operator) method. Levels of lipid and small metabolites were significantly altered and glycerophospholipids comprised a significant fraction of altered species. These changes correlate with altered expression of lipid metabolic genes, with most genes showing decreased expression. However, rapid upregulation of PG(22:6/22:6) level appeared to be a hitherto unknown feature of the metabolic shift observed in UUO. Using LASSO and SAM (significance analysis of microarrays), we identified a set of well-measured metabolites that accurately predicted UUO-induced renal damage that was detectable by 12 h after UUO, prior to apparent histological changes. Thus, DESI-MS could serve as a useful adjunct to histology in identifying renal damage and demonstrates early and broad changes in membrane associated lipids.

A long wait: barriers to discharge for long length of stay patients.

INTRODUCTION: Reducing long length of stay (LLOS, or inpatient stays lasting over 30 days) is an important way for hospitals to improve cost efficiency, bed availability and health outcomes. Discharge delays can cost hundreds to thousands of dollars per patient, and LLOS represents a burden on bed availability for other potential patients. However, most research studies investigating discharge barriers are not LLOS-specific. Of those that do, nearly all are limited by further patient subpopulation focus or small sample size. To our knowledge, our study is the first to describe LLOS discharge barriers in an entire Department of Medicine. METHODS: We conducted a chart review of 172 LLOS patients in the Department of Medicine at an academic tertiary care hospital and quantified the most frequent causes of delay as well as factors causing the greatest amount of delay time. We also interviewed healthcare staff for their perceptions on barriers to discharge. RESULTS: Discharge site coordination was the most frequent cause of delay, affecting 56% of patients and accounting for 80% of total non-medical postponement days. Goals of care issues and establishment of follow-up care were the next most frequent contributors to delay. CONCLUSION: Together with perspectives from interviewed staff, these results highlight multiple different areas of opportunity for reducing LLOS and maximising the care capacity of inpatient hospitals.

Building Partner Health Capacity with U.S. Military Forces: Enhancing AFSOC Health Engagement Missions.

The U.S. Air Force Special Operations Command (AFSOC) has developed an approach to planning for, assessing, and enhancing the effectiveness of missions to build partner capacity in health. These missions are systematic, long-term efforts to enhance the ability of governments in developing states that are important to U.S. interests to deliver essential medical, dental, and veterinary services to vulnerable populations. Helping to improve local public health and providing health services is expected to support the extension of good governance and counter insurgent and terrorist infiltration, recruitment, and exploitation. AFSOC believes that its health assets can be more effectively and systematically used by combatant commanders in achieving their theater security cooperation objectives, in conjunction with other organizations. This article documents the results of three research tasks undertaken to assist AFSOC in executing its mission: (1) placing health security in the context of U.S. strategy and security cooperation efforts; (2) drawing lessons from outside organizations on ways U.S. military forces can maximize their effectiveness in helping build partner health capacity; (3) developing a framework for planning and executing partner health capacity missions. Key findings are presented, along with recommendations for maximizing the effectiveness of efforts to build partner health capacity.