Helicobacter pylori FlgN binds its substrate FlgK and the flagellum ATPase FliI in a similar manner observed for the FliT chaperone.

In bacterial flagellum biogenesis, secretion of the hook-filament junction proteins FlgK and FlgL and completion of the flagellum requires the FlgN chaperone. Similarly, the related FliT chaperone is necessary for the secretion of the filament cap protein FliD and binds the flagellar export gate protein FlhA and the flagellum ATPase FliI. FlgN and FliT require FliJ for effective substrate secretion. In Helicobacter pylori, neither FlgN, FliT, nor FliJ have been annotated. We demonstrate that the genome location of HP1120 is identical to that of flgN in other flagellated bacteria and that HP1120 is the homolog of Campylobacter jejuni FlgN. A modeled HP1120 structure contains three α-helices and resembles the FliT chaperone, sharing a similar substrate-binding pocket. Using pulldowns and thermophoresis, we show that both HP1120 and a HP1120Δ126-144 deletion mutant bind to FlgK with nanomolar affinity, but not to the filament cap protein FliD, confirming that HP1120 is FlgN. Based on size-exclusion chromatography and multi-angle light scattering, H. pylori FlgN binds to FlgK with 1:1 stoichiometry. Overall structural similarities between FlgN and FliT suggest that substrate recognition on FlgN primarily involves an antiparallel coiled-coil interface between the third helix of FlgN and the C-terminal helix of the substrate. A FlgNΔ126-144 N100A, Y103A, S111I triple mutant targeting this interface significantly impairs the binding of FlgK. Finally, we demonstrate that FlgNΔ126-144 , like FliT, binds with sub-micromolar affinity to the flagellum ATPase FliI or its N-terminal domain. Hence FlgN and FliT likely couple delivery of low-abundance export substrates to the flagellum ATPase FliI.

Autoantibodies Neutralizing Type III Interferons Are Uncommon in Patients with Severe Coronavirus Disease 2019 Pneumonia.

Autoantibodies (AABs) neutralizing type I interferons (IFN) underlie about 15% of cases of critical coronavirus disease 2019 (COVID-19) pneumonia. The impact of autoimmunity toward type III IFNs remains unexplored. We included samples from 1,002 patients with COVID-19 (50% with severe disease) and 1,489 SARS-CoV-2-naive individuals. We studied the prevalence and neutralizing capacity of AABs toward IFNλ and IFNα. Luciferase-based immunoprecipitation method was applied using pooled IFNα (subtypes 1, 2, 8, and 21) or pooled IFNλ1-IFNλ3 as antigens, followed by reporter cell-based neutralization assay. In the SARS-CoV-2-naive cohort, IFNλ AABs were more common (8.5%) than those targeting IFNα2 (2.9%) and were related with older age. In the COVID-19 cohort the presence of autoreactivity to IFNλ did not associate with severe disease [odds ratio (OR) 0.84; 95% confidence interval (CI) 0.40-1.73], unlike to IFNα (OR 4.88; 95% CI 2.40-11.06; P < 0.001). Most IFNλ AAB-positive COVID-19 samples (67%) did not neutralize any of the 3 IFNλ subtypes. Pan-IFNλ neutralization occurred in 5 patients (0.50%), who all suffered from severe COVID-19 pneumonia, and 4 of them neutralized IFNα2 in addition to IFNλ. Overall, AABs to type III IFNs are rarely neutralizing, and do not seem to predispose to severe COVID-19 pneumonia on their own.

Blunt traumatic female urethral and bladder neck injuries: a 15-year single-institution experience.

PURPOSE: To describe our experience in the management and outcomes of female patients with urethral or bladder neck (BN) injury at a high-volume Level 1 trauma center. METHODS: A retrospective chart review of all female patients with urethral or BN injury by blunt trauma mechanism admitted to a Level 1 trauma center between 2005 and 2019 was performed. RESULTS: Ten patients met study criteria with median age 36.5 years. All had concomitant pelvic fractures. All injuries were confirmed operatively, with no delayed diagnoses. Two patients were lost to follow up. One patient was not eligible for early repair of urethral injury and had two repairs of a urethrovaginal fistula. Two of seven (29%) patients who underwent early repair of their injury had an early Clavien grade > 2 complication, with none reporting long-term complications at median follow-up of 15.2 months. CONCLUSIONS: Intraoperative evaluation is critical in the diagnosis of female urethral and BN injury. In our experience, acute surgical complications are not uncommon after the management of such injuries. However, there were no reported long-term complications in those patients who had prompt management of their injury. This aggressive diagnostic and surgical strategy is instrumental in attaining excellent surgical outcomes.

Functional outcomes of Fournier's gangrene: a multi-institutional experience.

INTRODUCTION: Fournier's gangrene (FG), is a progressive, necrotizing soft tissue infection of the external genitalia, perineum, and/or anorectal region. How treatment and recovery from FG impacts quality of life related to sexual and general health is poorly characterized. Our purpose is to evaluate the long term impact of FG on overall and sexual quality of life using standardized questionnaires through a multi-institutional observational study. MATERIALS AND METHODS: Multi-institutional retrospective data were collected by standardized questionnaires on patient-reported outcome measures including the Changes in Sexual Functioning Questionnaire (CSFQ) and the Veterans RAND 36 (VR-36) survey of general health-related quality of life. Data were collected via telephone call, email, and certified mail, with a 10% response rate. There was no incentive for patient participation. RESULTS: Thirty-five patients responded to the survey, with 9 female and 26 male patients. All patients in the study underwent surgical debridement between 2007-2018 at three tertiary care centers. Further reconstructions were performed for 57% of respondents. Values for respondents with overall lower sexual function were reduced in all component categories (pleasure, desire/ frequency, desire/interest, arousal/excitement, orgasm/ completion), and trended toward male sex, older age, longer time from initial debridement to reconstruction, and poorer self-reported general health-related quality of life metrics. CONCLUSION: FG is associated with high morbidity and significant decreases in quality of life across general and sexual functional domains.

Clinical and Demographic Profiles of Home Care Patients With Alzheimer's Disease and Related Dementias: Implications for Information Transfer Across Care Settings.

Home health care (HHC) clinicians serving individuals with Alzheimer's disease and related dementias (ADRD) do not always have information about the person's ADRD diagnosis, which may be used to improve the HHC plan of care. This retrospective cohort study examined characteristics of 56,652 HHC patients with varied documentation of ADRD diagnoses. Data included clinical assessments and Medicare claims for a 6-month look-back period and 4-year follow-up. Nearly half the sample had an ADRD diagnosis observed in the claims either prior to or following the HHC admission. Among those with a prior diagnosis, 63% did not have it documented on the HHC assessment; the diagnosis may not have been known to the HHC team or incorporated into the care plan. Patients with ADRD had heightened risk for adverse outcomes (e.g., urinary tract infection and aspiration pneumonia). Interoperable data across health care settings should include ADRD-specific elements about diagnoses, symptoms, and risk factors.

Mitochondrial copper and phosphate transporter specificity was defined early in the evolution of eukaryotes.

The mitochondrial carrier family protein SLC25A3 transports both copper and phosphate in mammals, yet in Saccharomyces cerevisiae the transport of these substrates is partitioned across two paralogs: PIC2 and MIR1. To understand the ancestral state of copper and phosphate transport in mitochondria, we explored the evolutionary relationships of PIC2 and MIR1 orthologs across the eukaryotic tree of life. Phylogenetic analyses revealed that PIC2-like and MIR1-like orthologs are present in all major eukaryotic supergroups, indicating an ancient gene duplication created these paralogs. To link this phylogenetic signal to protein function, we used structural modeling and site-directed mutagenesis to identify residues involved in copper and phosphate transport. Based on these analyses, we generated an L175A variant of mouse SLC25A3 that retains the ability to transport copper but not phosphate. This work highlights the utility of using an evolutionary framework to uncover amino acids involved in substrate recognition by mitochondrial carrier family proteins.

Getting out what you put in: Copper in mitochondria and its impacts on human disease.

Mitochondria accumulate copper in their matrix for the eventual maturation of the cuproenzymes cytochrome c oxidase and superoxide dismutase. Transport into the matrix is achieved by mitochondrial carrier family (MCF) proteins. The major copper transporting MCF described to date in yeast is Pic2, which imports the metal ion into the matrix. Pic2 is one of ~30 MCFs that move numerous metabolites, nucleotides and co-factors across the inner membrane for use in the matrix. Genetic and biochemical experiments showed that Pic2 is required for cytochrome c oxidase activity under copper stress, and that it is capable of transporting ionic and complexed forms of copper. The Pic2 ortholog SLC25A3, one of 53 mammalian MCFs, functions as both a copper and a phosphate transporter. Depletion of SLC25A3 results in decreased accumulation of copper in the matrix, a cytochrome c oxidase defect and a modulation of cytosolic superoxide dismutase abundance. The regulatory roles for copper and cuproproteins resident to the mitochondrion continue to expand beyond the organelle. Mitochondrial copper chaperones have been linked to the modulation of cellular copper uptake and export and the facilitation of inter-organ communication. Recently, a role for matrix copper has also been proposed in a novel cell death pathway termed cuproptosis. This review will detail our understanding of the maturation of mitochondrial copper enzymes, the roles of mitochondrial signals in regulating cellular copper content, the proposed mechanisms of copper transport into the organelle and explore the evolutionary origins of copper homeostasis pathways.

Effects of employer management on employee recruitment, satisfaction, engagement, and retention on large US dairy farms.

Lack of employee engagement and satisfaction and high turnover rate of employees are major problems on some US dairy farms. Farm adoption of human resource management (HRM) practices varies widely. Using feedback from 168 employees from 12 large dairy farms, our objectives were to understand employee perceptions of HRM strengths and weaknesses and their influence on (1) employee satisfaction, (2) retention of employees, (3) willingness of employees to recommend the farm as a place to work, and (4) level of employee engagement on the farm. Employees who rated their employers higher for almost any management-related question (MRQ) were more satisfied in their jobs and more likely to recommend their place of work to other potential employees. Employees reported a higher intention to stay on the farm when employers scored higher on MRQs connected to employer-employee relationships. Employees who rated "Relationships" (a component consisting of 5 MRQs) higher were more likely to have a higher rate of satisfaction, were more likely to intend to stay at their job, and were more likely to recommend their place of work to others. No single management question was positively related to employee engagement (as measured by employees having and sharing ideas to improve the business); however, ethnicity, gender, job role, duration of employment, and employee's self-appraisal of their desire to learn and commitment to the farm were each associated with engagement. Female employees were less likely to provide ideas to their employers (compared with male employees), as were Spanish-speaking employees (compared with English-speaking employees). Differences between Spanish- and English-speaking employees were also present in measures such as intention to stay (shorter) and willingness to recommend the farm as a place to work (higher). Employees who rated themselves higher on their desire to learn and commitment to the farm were more likely to provide ideas to their employers, as were longer-term employees. In conclusion, we inferred that dairy farm management can improve employee retention and engagement through improved use of HRM practices.

Risk Factors for Long-term Mortality and Patterns of End-of-Life Care Among Medicare Sepsis Survivors Discharged to Home Health Care.

Importance: Despite a growing recognition of the increased mortality risk among sepsis survivors, little is known about the patterns of end-of-life care among this population. Objective: To describe patterns of end-of-life care among a national sample of sepsis survivors and identify factors associated with long-term mortality risk and hospice use. Design, Setting, and Participants: This cohort study assessed sepsis survivors who were Medicare fee-for-service beneficiaries discharged to home health care using national Medicare administrative, claims, and home health assessment data from 2013 to 2014. The initial and final primary analyses were conducted in July 2017 and from July to August 2019, respectively. Exposures: Sepsis hospital discharge and 1 or more home health assessments within 1 week. Main Outcomes and Measures: Outcomes were 1-year mortality among all sepsis survivors and hospitalization in the last 30 days of life, death in an acute care hospital, and hospice use among decedents. Multivariate logistic regression was used to identify factors associated with 1-year mortality and hospice use. Results: Among 87 581 sepsis survivors who were Medicare fee-for-service beneficiaries discharged to home health care, 49 323 (56.3%) were aged 75 years or older, 69 499 (79.4%) were non-Hispanic white, and 48 472 (55.3%) were female. Among the total survivors, 24 423 (27.9%) people died within 1 year of discharge, with a median (interquartile range) survival time of 119 (51-220) days. Among these decedents, 16 684 (68.2%) were hospitalized in the last 30 days of life, 6560 (26.8%) died in an acute care hospital, and 12 573 (51.4%) were enrolled in hospice, with 5729 (45.6%) using hospice for 7 or fewer days. Several factors were associated with 1-year mortality, including a cancer diagnosis (odds ratio [OR], 3.66; 95% CI, 3.50-3.83; P < .001), multiple dependencies of activities of daily living or instrumental activities of daily living (OR, 2.80; 95% CI, 2.57-3.05; P < .001), and an overall poor health status (OR, 2.21; 95% CI, 2.01-2.44; P < .001) documented on home health assessment. Among the decedents, cancer was associated with hospice use (OR, 2.25; 95% CI, 2.11-2.41; P < .001), patients aged 85 years or older (OR, 1.49; 95% CI, 1.37-1.61; P < .001), and living in an assisted living setting (OR, 1.93; 95% CI, 1.69-2.19; P < .001). Conclusions and Relevance: The findings of this study suggest that death within 1 year after sepsis discharge may be common among Medicare beneficiaries discharged to home health care. Although 1 in 2 decedents used hospice, aggressive care near the end of life and late hospice referral were common. Readily identifiable risk factors suggest opportunities to target efforts to improve palliative and end-of-life care among high-risk sepsis survivors.

Role of Neutrophil Extracellular Traps Regarding Patients at Risk of Increased Disease Activity and Cardiovascular Comorbidity in Systemic Lupus Erythematosus.

OBJECTIVE: Neutrophil extracellular traps (NET) are essential in host defense, but are also linked to inflammation and autoimmunity, including in systemic lupus erythematosus (SLE). We recently described that immune complexes (IC) induce NET formation, promoting SLE-like disease in mice. In the current study, we investigated, for the first time to our knowledge, the role of NET in human SLE and their association with disease activity and severity. METHODS: Levels of NET (myeloperoxidase-DNA complexes) were analyzed in plasma from 4 cross-sectional SLE cohorts (n = 44-142), 1 longitudinal SLE cohort (n = 47), and healthy individuals (n = 100) using ELISA. Type I interferon activity was determined using a cell reporter system. RESULTS: Patients with SLE had elevated levels of NET in circulation compared to healthy controls (p < 0.01). NET levels identified patients with a severe disease phenotype characterized by IC-driven nephritis (p < 0.05). Though not associated with current disease activity (p = 0.20), levels of NET were associated with future increase in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) within 3 months (OR 1.75, p = 0.01), as well as an overall heightened SLEDAI over 1 year (p < 0.01). Finally, levels of NET were associated with arterial events (OR 5.0, p = 0.02) and endothelial cell activation (p < 0.001). CONCLUSION: NET levels are elevated in patients with SLE, associated with IC-driven disease. NET levels provide significant clinical value in identifying patients at risk of active disease and/or severe disease, including nephritis and cardiovascular disease, and may allow for early interventions.

Does Early Follow-Up Improve the Outcomes of Sepsis Survivors Discharged to Home Health Care?

BACKGROUND: There is little evidence to guide the care of over a million sepsis survivors following hospital discharge despite high rates of hospital readmission. OBJECTIVE: We examined whether early home health nursing (first visit within 2 days of hospital discharge and at least 1 additional visit in the first posthospital week) and early physician follow-up (an outpatient visit in the first posthospital week) reduce 30-day readmissions among Medicare sepsis survivors. DESIGN: A pragmatic, comparative effectiveness analysis of Medicare data from 2013 to 2014 using nonlinear instrumental variable analysis. SUBJECTS: Medicare beneficiaries in the 50 states and District of Columbia discharged alive after a sepsis hospitalization and received home health care. MEASURES: The outcomes, protocol parameters, and control variables were from Medicare administrative and claim files and the home health Outcome and Assessment Information Set (OASIS). The primary outcome was 30-day all-cause hospital readmission. RESULTS: Our sample consisted of 170,571 mostly non-Hispanic white (82.3%), female (57.5%), older adults (mean age, 76 y) with severe sepsis (86.9%) and a multitude of comorbid conditions and functional limitations. Among them, 44.7% received only the nursing protocol, 11.0% only the medical doctor protocol, 28.1% both protocols, and 16.2% neither. Although neither protocol by itself had a statistically significant effect on readmission, both together reduced the probability of 30-day all-cause readmission by 7 percentage points (P=0.006; 95% confidence interval=2, 12). CONCLUSIONS: Our findings suggest that, together, early postdischarge care by home health and medical providers can reduce hospital readmissions for sepsis survivors.

Structure of Ddi2, a highly inducible detoxifying metalloenzyme from Saccharomyces cerevisiae.

Cyanamide (H2N-CN) is used to break bud dormancy in woody plants and to deter alcohol use in humans. The biological effects of cyanamide in both these cases require the enzyme catalase. We previously demonstrated that Saccharomyces cerevisiae exposed to cyanamide resulted in strong induction of DDI2 gene expression. Ddi2 enzymatically hydrates cyanamide to urea and belongs to the family of HD-domain metalloenzymes (named after conserved active-site metal-binding His and Asp residues). Here, we report the X-ray structure of yeast Ddi2 to 2.6 Å resolution, revealing that Ddi2 is a dimeric zinc metalloenzyme. We also confirm that Ddi2 shares structural similarity with other known HD-domain proteins. HD residues His-55, His-88, and Asp-89 coordinate the active-site zinc, and the fourth zinc ligand is a water/hydroxide molecule. Other HD domain enzymes have a second aspartate metal ligand, but in Ddi2 this residue (Thr-157) does not interact with the zinc ion. Several Ddi2 active-site point mutations exhibited reduced catalytic activity. We kinetically and structurally characterized H137N and T157V mutants of Ddi2. A cyanamide soak of the Ddi2-T157V enzyme revealed cyanamide bound directly to the Zn2+ ion, having displaced the zinc-bound water molecule. The mode of cyanamide binding to Ddi2 resembles cyanamide binding to the active-site zinc of carbonic anhydrase, a known cyanamide hydratase. Finally, we observed that the sensitivity of ddi2Δ ddi3Δ to cyanamide was not rescued by plasmids harboring ddi2-H137N or ddi2-TI57V variants, demonstrating that yeast cells require a functioning cyanamide hydratase to overcome cyanamide-induced growth defects.

Predictors of Hospice Enrollment for Patients With Advanced Heart Failure and Effects on Health Care Use.

OBJECTIVES: This study sought to: 1) identify the predictors of hospice enrollment for patients with heart failure (HF); and 2) determine the impact of hospice enrollment on health care use. BACKGROUND: Patients with HF rarely enroll in hospice. Little is known about how hospice affects this group's health care use. METHODS: Using a propensity score-matched sample of Medicare decedents with ≥2 HF discharges within 6 months, an Outcome and Assessment Information Set (OASIS) assessment, and subsequent death, we used Medicare administrative, claims, and patient assessment data to compare hospitalizations, intensive care unit stays, and emergency department visits for those beneficiaries who enrolled in hospice and those who did not. RESULTS: The propensity score-matched sample included 3,067 beneficiaries in each group with a mean age of 82 years; 53% were female, and 15% were Black, Asian, or Hispanic. For objective 1, there were no differences in the characteristics, symptom burden, or functional status between groups that were associated with hospice enrollment. For objective 2, in the 6 months after the second HF discharge, the hospice group had significantly fewer emergency department visits (2.64 vs. 2.82; p = 0.04), hospital days (3.90 vs. 4.67; p < 0.001), and intensive care unit stays (1.25 vs. 1.51; p < 0.001); they were less likely to die in the hospital (3% vs. 56%; p < 0.001), and they had longer median survival (80 days vs. 71 days; log-rank test p = 0.004). CONCLUSIONS: Beneficiaries' characteristics, including symptom burden and functional status, do not predict hospice enrollment. Those patients who enrolled in hospice used less health care, survived longer, and were less likely to die in the hospital. A tailored hospice model may be needed to increase enrollment and offer benefits to patients with HF.

Evaluation by employees of employee management on large US dairy farms.

Employees, many of whom are not native English speakers, perform the majority of work on large US dairy farms. Although management of employees is a critical role of dairy owners and managers, factors that improve employee engagement and retention are not well known. Objectives were to (1) identify key dairy farm employee management issues based on employee perceptions, (2) evaluate strengths and weaknesses of farms based on employee responses, (3) investigate differences between Latino and English-speaking employees, and (4) investigate differences in perception between employers and employees. Employees from 12 US dairy farms (each with a minimum of 10 employees) were interviewed by phone following a questionnaire provided. Employees provided their responses to 21 Likert scale questions and 8 open-ended questions. There was a wide range in employee turnover among farms (<10 to >100%). Latino employees had much shorter tenure and were more often employed in milking and livestock care than English-speaking employees. Employee perceptions differed among farms regarding whether they would recommend their farm as a place to work, teamwork within the dairy, whether rules were fairly applied, availability of tools and equipment, clear lines of supervision, and recognition for good work in the previous 15 d. Latino employees (n = 91) were more positive in many of these measures than their English-speaking counterparts (n = 77) but less often provided ideas to their employer on how to improve the business. Employers, surveyed on how they thought their employees would answer, underestimated employee responses on several questions, particularly the interest of employees in learning about dairy. When asked to cite 3 goals of the operation, there were differences among owners, managers, and employees. Although employees rated their commitment to the farm and their interest in learning as high, based on turnover, there was an obvious disparity between reality and ideal employee management. Consequently, employers should act on identified management shortfalls to improve employee retention.

Patient-derived mutations within the N-terminal domains of p85α impact PTEN or Rab5 binding and regulation.

The p85α protein regulates flux through the PI3K/PTEN signaling pathway, and also controls receptor trafficking via regulation of Rab-family GTPases. In this report, we determined the impact of several cancer patient-derived p85α mutations located within the N-terminal domains of p85α previously shown to bind PTEN and Rab5, and regulate their respective functions. One p85α mutation, L30F, significantly reduced the steady state binding to PTEN, yet enhanced the stimulation of PTEN lipid phosphatase activity. Three other p85α mutations (E137K, K288Q, E297K) also altered the regulation of PTEN catalytic activity. In contrast, many p85α mutations reduced the binding to Rab5 (L30F, I69L, I82F, I177N, E217K), and several impacted the GAP activity of p85α towards Rab5 (E137K, I177N, E217K, E297K). We determined the crystal structure of several of these p85α BH domain mutants (E137K, E217K, R262T E297K) for bovine p85α BH and found that the mutations did not alter the overall domain structure. Thus, several p85α mutations found in human cancers may deregulate PTEN and/or Rab5 regulated pathways to contribute to oncogenesis. We also engineered several experimental mutations within the p85α BH domain and identified L191 and V263 as important for both binding and regulation of Rab5 activity.

Insight into the PTEN - p85α interaction and lipid binding properties of the p85α BH domain.

The phosphatidylinositol 3-kinase (PI3K) pathway plays a key role in regulating cell growth and cell survival and is frequently deregulated in cancer cells. p85α regulates the p110α lipid kinase, and also stabilizes and stimulates PTEN, the lipid phosphatase that downregulates this pathway. In this report, we determined that the p85α BH domain binds several phosphorylated phosphoinositide lipids, an interaction that could help localize p85α to membranes rich in these lipids. We also identified key residues responsible for mediating PTEN - p85α complex formation. Based on these experimental results, a docking model for the PTEN - p85α BH domain complex was developed that is consistent with the known binding interactions for both PTEN and p85α. This model involves extensive side-chain and peptide backbone contacts between both the PASE and C2 domains of PTEN with the p85α BH domains. The p85α BH domain residues shown to be important for PTEN binding were p85α residues E212, Q221, K225, R228 and H234. We also verified experimentally the importance of PTEN-E91 in mediating the interaction with the p85α BH domain. These results shed new light on the mechanism of PTEN regulation by p85α.

Hospice Enrollment in Patients With Advanced Heart Failure Decreases Acute Medical Service Utilization.

BACKGROUND: Patients with advanced heart failure (HF) enroll in hospice at low rates, and data on their acute medical service utilization after hospice enrollment is limited. METHODS AND RESULTS: We performed a descriptive analysis of Medicare fee-for-service beneficiaries, with at least one home health claim between July 1, 2009, and June 30, 2010, and at least 2 HF hospitalizations between July 1, 2009, and December 31, 2009, who subsequently enrolled in hospice between July 1, 2009, and December 31, 2009. We estimated panel-negative binomial models on a subset of beneficiaries to compare their acute medical service utilization before and after enrollment. Our sample size included 5073 beneficiaries: 55% were female, 45% were ≥85 years of age, 13% were non-white, and the mean comorbidity count was 2.38 (standard deviation 1.22). The median number of days between the second HF hospital discharge and hospice enrollment was 45. The median number of days enrolled in hospice was 15, and 39% of the beneficiaries died within 7 days of enrollment. During the study period, 11% of the beneficiaries disenrolled from hospice at least once. The adjusted mean number of hospital, intensive care unit, and emergency room admissions decreased from 2.56, 0.87, and 1.17 before hospice enrollment to 0.53, 0.19, and 0.76 after hospice enrollment. CONCLUSIONS: Home health care Medicare beneficiaries with advanced HF who enrolled in hospice had lower acute medical service utilization after their enrollment. Their pattern of hospice use suggests that earlier referral and improved retention may benefit this population. Further research is necessary to understand hospice referral and palliative care needs of advanced HF patients.

Reducing Readmissions among Heart Failure Patients Discharged to Home Health Care: Effectiveness of Early and Intensive Nursing Services and Early Physician Follow-Up.

OBJECTIVE: To compare the effectiveness of two "treatments"-early, intensive home health nursing and physician follow-up within a week-versus less intense and later postacute care in reducing readmissions among heart failure (HF) patients discharged to home health care. DATA SOURCES: National Medicare administrative, claims, and patient assessment data. STUDY DESIGN: Patients with a full week of potential exposure to the treatments were followed for 30 days to determine exposure status, 30-day all-cause hospital readmission, other health care use, and mortality. An extension of instrumental variables methods for nonlinear statistical models corrects for nonrandom selection of patients into treatment categories. Our instruments are the index hospital's rate of early aftercare for non-HF patients and hospital discharge day of the week. DATA EXTRACTION METHODS: All hospitalizations for a HF principal diagnosis with discharge to home health care between July 2009 and June 2010 were identified from source files. PRINCIPAL FINDINGS: Neither treatment by itself has a statistically significant effect on hospital readmission. In combination, however, they reduce the probability of readmission by roughly 8 percentage points (p < .001; confidence interval = -12.3, -4.1). Results are robust to changes in implementation of the nonlinear IV estimator, sample, outcome measure, and length of follow-up. CONCLUSIONS: Our results call for closer coordination between home health and medical providers in the clinical management of HF patients immediately after hospital discharge.