Risk factors for adverse events induced by immune checkpoint inhibitors in patients with non-small-cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause serious immune-related adverse events (irAEs). This study aimed to identify risk factors for all types of irAEs induced by ICIs in patients with non-small-cell lung cancer (NSCLC), by systematic review and meta-analyses. METHODS: A systematic search was performed in Pubmed, Embase and Web of Science by two independent reviewers. Studies were selected that included patients with NSCLC and evaluated characteristics of patients with and without irAEs induced by ICIs. Quality and risk of bias of the selected studies were assessed. Random effects meta-analyses were conducted to estimate pooled odds ratios (ORs) for risk factors of developing all type of irAEs, and separately for pneumonitis, interstitial lung disease and severe irAEs. With the objective of exploring sources of heterogeneity, stratified analyses were performed by quality and region. RESULTS: 25 studies met the inclusion criteria. In total, the data of 6696 patients were pooled. 33 different risk factors for irAEs were reported. irAEs of interest were reported for 1653 (25%) of the patients. Risk factors related to the development of irAEs were: C-reactive protein, neutrophil lymphocyte ratio (NLR), use of PD-1 inhibitor, high PD-L1 expression, an active or former smoking status, ground glass attenuation, and a better treatment response. CONCLUSION: The identified risk factors for the development of these irAEs are mostly related to the alteration of the immune system, proinflammatory states and loss of immunological self-tolerance. Patients identified as having a higher risk for irAEs should be monitored more closely.

On the relations between focus, experience, and hospital performance.

BACKGROUND: In the United States, a long-standing debate has existed over advantages/disadvantages of general versus specialty hospitals. A recent stream of research has investigated whether general hospitals accrue performance benefits from a focus strategy; a strategy of specializing in certain clinical conditions while remaining a multiproduct firm. In contrast, a substantial and long-standing body of research on hospitals has been concerned with the absolute volume of cases in a service area as an indication of experience based largely on the idea that absolute volume confers learning opportunities. PURPOSE: We investigated whether hospital focus and experience in a service area have complementary effects or are largely substitutive for hospital performance. METHODOLOGY/APPROACH: Key data sources were patient discharge records and hospital discharge profiles from California's Office of Statewide Health Policy and Development for years 2010-2014. We specified hospital focus as the proportion of total cardiology-related discharges and hospital experience as the cumulative volume of cardiology-related discharges for each hospital. Performance was specified using quality (inpatient mortality and 30-day readmission) and efficiency (length of stay and cost) patient-level performance metrics. We analyzed the data using logistic and log-linear ordinary least squares regression models. RESULTS: Study results generally supported our hypotheses that focus and experience are related to better quality and efficiency performance and that the effects are largely substitutive for hospitals. CONCLUSION: Our study extends the literature by finding that hospitals exhibit distinct and stable patterns regarding their positioning on focus and experience and that these patterns have important implications for hospitals' performance in terms of quality and efficiency. PRACTICE IMPLICATIONS: Many general hospitals in the United States may be stretched too thin across service areas for which they lack necessary patient volumes for clinical proficiency. A viable alternative is to select a limited set of service areas on which to focus.

Effects of Physician Experience, Specialty Training, and Self-referral on Inappropriate Diagnostic Imaging.

BACKGROUND: Although previous research has demonstrated high rates of inappropriate diagnostic imaging, the potential influence of several physician-level characteristics is not well established. OBJECTIVE: To examine the influence of three types of physician characteristics on inappropriate imaging: experience, specialty training, and self-referral. DESIGN: A retrospective analysis of over 70,000 MRI claims submitted for commercially insured individuals. Physician characteristics were identified through a combination of administrative records and primary data collection. Multi-level modeling was used to assess relationships between physician characteristics and inappropriate MRIs. SETTING: Massachusetts PARTICIPANTS: Commercially insured individuals who received an MRI between 2010 and 2013 for one of three conditions: low back pain, knee pain, and shoulder pain. MEASUREMENTS: Guidelines from the American College of Radiology were used to classify MRI referrals as appropriate/inappropriate. Experience was measured from the date of medical school graduation. Specialty training comprised three principal groups: general internal medicine, family medicine, and orthopedics. Two forms of self-referral were examined: (a) the same physician who ordered the procedure also performed it, and (b) the physicians who ordered and performed the procedure were members of the same group practice and the procedure was performed outside the hospital setting. RESULTS: Approximately 23% of claims were classified as inappropriate. Physicians with 10 or less years of experience had significantly higher odds of ordering inappropriate MRIs. Primary care physicians were almost twice as likely to order an inappropriate MRI as orthopedists. Self-referral was not associated with higher rates of inappropriate MRIs. LIMITATIONS: Classification of MRIs was conducted with claims data. Not all self-referred MRIs could be detected. CONCLUSIONS: Inappropriate imaging continues to be a driver of wasteful health care spending. Both physician experience and specialty training were highly associated with inappropriate imaging.

Correction to: Effects of Physician Experience, Specialty Training, and Self-referral on Inappropriate Diagnostic Imaging.

There were some errors in the variables in this paper.

Effectiveness of a Modular Cognitive-Behavioral Skills Curriculum in High-Risk Justice-Involved Youth.

The aim of this study was to evaluate the effectiveness of a flexible modular cognitive-behavioral theory (CBT) skills curriculum delivered by paraprofessionals in a community organization targeting high-risk justice-involved youth. Programmatic data were collected from 980 high-risk young men (Mage, 21.12; SD, 2.30), and Cox proportional hazards regression was used. The results showed that compared with young men with no CBT encounters, those with one or more CBT encounters had a 66% (hazard ratio [HR], 0.34; 95% confidence interval [CI], 0.28-0.42; p < 0.001) lower risk of unenrolling from programming, 65% (HR, 1.65; 95% CI, 1.29-2.12; p < 0.001) higher risk of obtaining a job, and no difference in risk of engaging in new criminal activity while enrolled in programming (HR, 0.99; 95% CI, 0.78-1.25; p = 0.918), despite higher risk factors. Training paraprofessionals to deliver CBT skills to high-risk populations is effective and has scalability potential.

Magnitude and financial implications of inappropriate diagnostic imaging for three common clinical conditions.

OBJECTIVE: To quantify the level of adherence to imaging guidelines for three common clinical indications for a commercially insured population. DESIGN: Retrospective analysis of administrative claims data for commercially insured individuals with diagnostic imaging claims (MRI and X-ray) for either uncomplicated low back pain, non-traumatic knee pain or non-traumatic shoulder pain. SETTING: The State of Massachusetts for 2010 and 2013. PARTICIPANTS: Adults with no chronic conditions and without evidence of prior management in the 12 months preceding to the initial office visit for each of the clinical indications. MAIN OUTCOMES MEASURES: Imaging procedures performed within 30 days of the initial office visit were classified as appropriate or inappropriate according to adherence to imaging guidelines from American College of Radiology. RESULTS: More than 60% of lumbar spine MRI's were deemed inappropriate in 2010 and in 2013. Over 30% of MRI's for shoulder pain and knee pain were inappropriate in 2010 and in 2013. Patients age 18-59 with inappropriate imaging claims had significantly lower rates of surgical procedures within 90 days of imaging than those with appropriate imaging. Inappropriate imaging accounted for over 20% of annual imaging costs for the three clinical indications. CONCLUSIONS: Reducing inappropriate imaging procedures can lead to substantial savings through the elimination of unnecessary and low value procedures. Increased awareness of and adherence to best practice guidelines should be a focus of efforts to cut waste in our healthcare system.

Impact of ACA Medicaid Expansion on Hospitals' Financial Status.

EXECUTIVE SUMMARY: The Patient Protection and Affordable Care Act's insurance reforms were expected to have significant and positive implications for hospital finances. In particular, state expansion of Medicaid programs held the promise of reducing hospitals' uncompensated care costs as a result of expanding health insurance to many previously uninsured individuals. Recent research indicates that in the early phases of Medicaid expansion, many hospitals did experience a substantial decline in uncompensated care costs. However, studies to date have not considered whether Medicaid expansion resulted in payment shortfalls that offset some of what hospitals saved from lower uncompensated care costs. We examined filings submitted by hospitals to the Internal Revenue Service (IRS)-one of the few publicly available sources of national data on both uncompensated care costs and Medicaid payment shortfalls. We also compared changes in uncompensated care costs and Medicaid payment shortfalls for hospitals in expansion states with those in nonexpansion states. Our findings indicate that state expansion of Medicaid led to substantial reductions in hospitals' uncompensated care costs, but the savings were offset somewhat by increased Medicaid payment shortfalls. Therefore, studies that focus only on reductions in uncompensated care costs can overstate the benefits of Medicaid expansion on hospitals finances.

Neonatal respiratory syncytial virus infection has an effect on lung inflammation and the CD4(+) CD25(+) T cell subpopulation during ovalbumin sensitization in adult mice.

In BALB/c adult mice, respiratory syncytial virus (RSV) infection enhances the degree of lung inflammation before and/or after ovalbumin (OVA) respiratory sensitization. However, it is unclear whether RSV infection in newborn mice has an effect on the immune response to OVA respiratory sensitization in adult mice. The aim of this study was to determine if RSV neonatal infection alters T CD4(+) population and lung inflammation during OVA respiratory sensitization in adult mice. BALB/c mice were infected with RSV on the fourth day of life and challenged by OVA 4 weeks later. We found that in adult mice, RSV neonatal infection prior to OVA sensitization reduces the CD4(+) CD25(+) and CD4(+) CD25(+) forkhead protein 3 (FoxP3)(+) cell populations in the lungs and bronchoalveolar lavage. Furthermore, it also attenuates the inflammatory infiltrate and cytokine/chemokine expression levels in the mouse airways. In conclusion, the magnitude of the immune response to a non-viral respiratory perturbation in adult mice is not enhanced by a neonatal RSV infection.

CCR9 Is a Key Regulator of Early Phases of Allergic Airway Inflammation.

Airway inflammation is the most common hallmark of allergic asthma. Chemokine receptors involved in leukocyte recruitment are closely related to the pathology in asthma. CCR9 has been described as a homeostatic and inflammatory chemokine receptor, but its role and that of its ligand CCL25 during lung inflammation remain unknown. To investigate the role of CCR9 as a modulator of airway inflammation, we established an OVA-induced allergic inflammation model in CCR9-deficient mice. Here, we report the expression of CCR9 and CCL25 as early as 6 hours post-OVA challenge in eosinophils and T-lymphocytes. Moreover, in challenged CCR9-deficient mice, cell recruitment was impaired at peribronchial and perivenular levels. OVA-administration in CCR9-deficient mice leads to a less inflammatory cell recruitment, which modifies the expression of IL-10, CCL11, and CCL25 at 24 hours after OVA challenge. In contrast, the secretion of IL-4 and IL-5 was not affected in CCR9-deficient mice compared to WT mice. These results demonstrate for the first time that CCR9 and CCL25 expressions are induced in the early stages of airway inflammation and they have an important role modulating eosinophils and lymphocytes recruitment at the first stages of inflammatory process, suggesting that they might be a potential target to regulate inflammation in asthma.

Hospital employment of physicians and supply chain performance: An empirical investigation.

BACKGROUND: As hospital employment of physicians becomes increasingly common in the United States, much speculation exists as to whether this type of arrangement will promote hospital operating efficiency in such areas as supply chain management. Little empirical research has been conducted to address this question. PURPOSE: The aim of this study was to provide an exploratory assessment of whether hospital employment of physicians is associated with better supply chain performance. Drawing from both agency and stewardship theories, we examined whether hospitals with a higher proportion of employed medical staff members have relatively better supply chain performance based on two performance measures, supply chain expenses and inventory costs. APPROACH: We conducted the study using a pooled, cross-sectional sample of hospitals located in California between 2007 and 2009. Key data sources were hospital annual financial reports from California's Office of Statewide Health Policy and Development and the American Hospital Association annual survey of hospitals. To examine the relationship between physician employment and supply chain performance, we specified physician employment as the proportion of total employed medical staff members as well as the proportion of employed medical staff members within key physician subgroups. We analyzed the data using generalized estimating equations. FINDINGS: Study results generally supported our hypothesis that hospital employment of physicians is associated with better supply chain performance. PRACTICAL IMPLICATIONS: Although the results of our study should be viewed as preliminary, the trend in the United States toward hospital employment of physicians may be a positive development for improved hospital operating efficiency. Hospital managers should also be attentive to training and educational resources that medical staff members may need to strengthen their role in supply chain activities.

The association of nutritional and inflammatory biomarkers with overall survival in patients with non-small-cell lung cancer treated with immune checkpoint inhibitors.

OBJECTIVES: Pretreatment biomarkers are needed to identify patients with non-small-cell lung cancer (NSCLC) likely to have worse survival. This ensures that only patients with a real chance of benefit receive immune checkpoint inhibitor (ICI) treatment. In this study, we examined the associations of baseline nutritional and inflammatory biomarkers with overall survival in a real-world cohort of NSCLC patients who received ICIs. MATERIALS AND METHODS: We used prospectively collected data from the OncoLifeS data biobank. The cohort included 500 advanced-stage NSCLC patients treated with ICIs from May 2015 to June 2021. Biomarkers were evaluated within 2 weeks before ICI treatment: neutrophil-to-lymphocyte ratio, C-reactive protein (CRP), Glasgow prognostic score, CRP/albumin ratio (CAR), prognostic nutritional index (PNI), and advanced lung cancer inflammation index. For each biomarker, low- and high-risk groups were defined using literature-based cut-offs. Adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were estimated using adjusted survival analysis. RESULTS: Most patients were male (60.8%), the mean baseline age was 65 ± 9 years, and 88% had stage IV disease. For each biomarker, low-risk patients had better overall survival (all, p < 0.001), with CAR and PNI showing the strongest associations. In multivariable analyses a combined CAR/PNI risk score had a stronger association with overall survival (aHR 3.09, 95% CI 2.36-4.06) than CAR alone (aHR 2.22, 95% CI 1.79-2.76) or PNI alone (aHR 2.09, 95% CI 1.66-2.61). CONCLUSION: These results highlight the potential value of nutritional and inflammatory biomarkers, in particular CAR and PNI, in identifying NSCLC patients with highest mortality risk before starting ICI treatment.

"For the first time I am seriously fighting burnout": clinician experiences with a challenging electronic health record transition.

Objectives: The Department of Veterans Affairs (VA) is transitioning from its legacy electronic health record (EHR) to a new commercial EHR in a nationwide, rolling-wave transition. We evaluated clinician and staff experiences to identify strategies to improve future EHR rollouts. Materials and Methods: We completed a convergent mixed-methods formative evaluation collecting survey and interview data to measure and describe clinician and staff experiences. Survey responses were analyzed using descriptive statistics; interview transcripts were coded using a combination of a priori and emergent codes followed by qualitative content analysis. Qualitative and quantitative findings were compared to provide a more comprehensive understanding of participant experience. Employees of specialty and primary care teams at the first nationwide EHR transition site agreed to participate in our study. We distributed surveys at 1-month pre-transition, 2 months post-transition, and 10 months post-transition to each of the 68 identified team members and completed longitudinal interviews with 30 of these individuals totaling 122 semi-structured interviews. Results: Interview participants reported profoundly disruptive experiences during the EHR transition that persisted at 1-year post implementation. Survey responses indicated training difficulties throughout the transition, and sharp declines (P ≤ .05) between pre- and post-go-live measures of EHR usability and increase in EHR burden that were perceived to be due in part to system inefficiencies, discordant positive messaging that initially ignored user challenges, and inadequate support for and attention to ongoing EHR issues. Participants described persistent high levels of stress associated with these disruptions. Discussion: Our findings highlight strategies to improve employee experiences during EHR transitions: (1) working with Oracle Cerner to resolve known issues and improve usability; (2) role-based training with opportunities for self-directed learning; (3) peer-led support systems and timely feedback on issues; (4) messaging that responds to challenges and successes; and (5) continuous efforts to support staff with issues and address clinician and staff stress and burnout. Conclusion: Our findings provide relevant strategies to navigate future EHR transitions while supporting clinical teams.

The multiple faces of CCL13 in immunity and inflammation.

CCL13/MCP-4, is a CC family chemokine that is chemoattractant for eosinophils, basophils, monocytes, macrophages, immature dendritic cells, and T cells, and its capable of inducing crucial immuno-modulatory responses through its effects on epithelial, muscular and endothelial cells. Similar to other CC chemokines, CCL13 binds to several chemokine receptors (CCR1, CCR2 and CCR3), allowing it to elicit different effects on its target cells. A number of studies have shown that CCL13 is involved in many chronic inflammatory diseases, in which it functions as a pivotal molecule involved in the selective recruitment of cell lineages to the inflamed tissues and their subsequent activation. Based on these studies, we suggest that blocking the actions of CCL13 can serve as a novel strategy for the generation of agents with anti-inflammatory activity. The main goal of this review is to present the current information about CCL13, its gene and protein structure and the roles of this chemokine during innate/adaptive immune responses in inflammatory diseases.

Quality of life after treatment with immune checkpoint inhibitors for lung cancer; the impact of age.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have revolutionized lung cancer treatment. However, it remains unclear as to whether changes in Health-Related Quality-of-Life (HRQoL) are associated with the age of lung cancer patients treated using ICIs. This study aimed to evaluate this possible association and to compare ICI-treated patients' HRQoL scores with normative data of an age-matched non-cancer general population. METHODS: Lung cancer patients from the OncoLifeS data-biobank were included if they were treated with ICIs, irrespective of other treatments, at the University Medical Center Groningen between 2015 and 2021 and had completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTCQLQ-C30), both at the start of ICI treatment and after six months. Association of age as a continuous variable (per 10 years) and changes in HRQoL scores between baseline and 6 months was assessed using multivariable regression analyses. Clinical relevance of differences in HRQoL scores between OncoLifeS and the general population was classified into trivial, small, medium, and large, for three age groups (<60, 60-69 and ≥ 70 years). RESULTS: 151 patients were included with a mean age of 65.8 years. An increase in age per 10 years was associated with a larger decrease in the summary HRQoL score(ß = -3.28,CI95%-6.42;-0.14), physical(ß = -4.8, CI95% -8.71;-0.88), cognitive(ß = -4.51,CI95%-8.24;-0.78), role functioning(ß = -5.41,CI95%-10.78;-0.05), symptom burden(ß = -3.66,CI95%-6.6;-0.73), and smaller negative changes in financial difficulties(ß = 6.5 95 % CI 3.16; 9.85). OncoLifeS HRQoL scores were lower than those of the general population and differences were most often classified as large and medium. CONCLUSION: Older lung cancer patients experience larger deteriorations in most HRQoL domains after 6 months of ICI treatment. Also, these patients showed significantly lower HRQoL scores compared to the general population.

Human eotaxin is a specific chemoattractant for eosinophil cells and provides a new mechanism to explain tissue eosinophilia.

Eotaxin is an eosinophil-specific chemoattractant that has been recently identified in rodent models of asthma and host response against tumors. To determine whether a similar molecule might play a role in human inflammatory diseases characterized by eosinophilia, we isolated the human eotaxin gene. We demonstrate that human eotaxin is an early response gene of cytokine-stimulated epithelial and endothelial cells, and is induced in peripheral blood eosinophils by interleukin-3. Eotaxin is directly chemotactic for eosinophils, but not mononuclear cells or neutrophils. Eotaxin messenger RNA accumulates markedly in the lesions of patients with inflammatory bowel disease (ulcerative colitis and Crohn's disease), but not in the lesions of patients with diverticulitis. These results now provide a mechanism involving eotaxin to explain the eosinophil infiltration seen in a variety of human disease; as such, an eotaxin antagonist may be a novel therapy for certain human diseases characterized by tissue eosinophilia.

Trichinella spiralis: intranasal immunization with attenuated Salmonella enterica carrying a gp43 antigen-derived 30mer epitope elicits protection in BALB/c mice.

Trichinellosis is a public health problem and is considered an emergent/re-emergent disease in various countries. The etiological agent of trichinellosis is the nematode Trichinella, which infects domestic animals such as pigs and horses, as well as wild animals and humans. A veterinary vaccine could be an option to control the disease in domestic animals. Although several vaccine candidates have shown promising results, a vaccine against trichinellosis remains unavailable to date. Attenuated Salmonella strains are especially attractive live vectors because they elicit mucosal immunity, which is known to be important for the control of Trichinella spiralis infection at the intestinal level and can be administered by oral or intranasal routes. In this study, the autotransporter ShdA was used to display, on the surface of the Salmonella enterica serovar Typhimurium SL3261, the 210-239 amino acid epitope, (designated as Ag30) derived from the 43 kDa glycoprotein of T. spiralis muscle larvae. The fusion protein elicited antibodies in BALB/c mice that were able to recognize the native epitope on the surface of T. spiralis muscle larvae. Mice immunized by intranasal route with the recombinant Salmonella induced a protective immune response against the T. spiralis challenge, reducing by 61.83% the adult burden at day eight postinfection. This immune response was characterized by the induction of antigen-specific IgG1 and of IL-5 production. This study demonstrates the usefulness of Salmonella as a carrier of nematode epitopes providing a surface display system for intestinal parasite vaccine applications.

Hospital Employment Of Physicians In Massachusetts Is Associated With Inappropriate Diagnostic Imaging.

The transition among many US physicians from independent practice to hospital employment has raised concerns about whether employed physicians will be more inclined to refer patients for hospital-based services that are unnecessary or inappropriate. Using claims data for 2009-16, we conducted a difference-in-differences analysis to investigate whether this form of hospital-physician integration is associated with inappropriate referrals for magnetic resonance imaging (MRI), a widely used mode of diagnostic imaging, for three common medical conditions: lower back pain, knee pain, and shoulder pain. Study findings indicate that the odds of a patient receiving an inappropriate MRI referral increased by more than 20 percent after a physician transitioned to hospital employment. Most patients who received an MRI referral by an employed physician obtained the procedure at the hospital where the referring physician was employed. These results point to hospital-physician integration as a potential driver of low-value care.

Molecular and biological characterization of the murine leukotriene B4 receptor expressed on eosinophils.

The movement of leukocytes into tissues is regulated by the local production of chemical mediators collectively referred to as chemoattractants. Although chemoattractants constitute a diverse array of molecules, including proteins, peptides, and lipids, they all appear to signal leukocytes through a related family of seven transmembrane-spanning G protein-coupled receptors. The eosinophil is a potent proinflammatory cell that is attracted into tissues during allergic inflammation, parasitic infection, and certain malignancies. Since the molecular mechanisms controlling eosinophil recruitment are incompletely understood, we performed a degenerate polymerase chain reaction on cDNA isolated from murine eosinophils to identify novel chemoattractant receptors. We report the isolation of a cDNA that encodes a 351-amino acid glycoprotein that is 78% identical to a human gene that has been reported to be a purinoceptor (P2Y7) and a leukotriene B4 (LTB4) receptor (BLTR). Chinese hamster ovary (CHO) cells transfected with this cDNA specifically bound [3H]LTB4 with a dissociation constant of 0.6 +/- 0.1 nM. Furthermore, LTB4 induced a dose-dependent intracellular calcium flux in transfected CHO cells. In contrast, [35S]dATP did not specifically bind to these transfectants. This mRNA was expressed at high levels in interleukin 5-exposed eosinophils, elicited peritoneal macrophages and neutrophils, and to a lesser extent interferon gamma stimulated macrophages. Low levels of expression were detected in the lung, lymph node, and spleen of unchallenged mice. Western blot analysis detected the mBLTR protein in murine eosinophils and alveolar macrophages as well as human eosinophils. In addition, elevated levels of mBLTR mRNA were found in the lungs of mice in a murine model of allergic pulmonary inflammation in a time course consistent with the influx of eosinophils. Our findings indicate that this murine receptor is an LTB4 receptor that is highly expressed on activated leukocytes, including eosinophils, and may play an important role in mediating eosinophil recruitment into inflammatory foci.

Murine monocyte chemoattractant protein (MCP)-5: a novel CC chemokine that is a structural and functional homologue of human MCP-1.

The chemokines are a large family of cytokines that control the recruitment of leukocytes in immune and inflammatory responses. We describe the isolation of a novel murine CC chemokine that, based on its biological and structural features, we have named monocyte chemoattractant protein (MCP)-5. MCP-5 mapped to the CC chemokine cluster on mouse chromosome 11 and was most closely related to human MCP-1 in structure (66% amino acid identity). Purified recombinant MCP-5 protein was a potent chemoattractant for peripheral blood monocytes, was only weakly active on eosinophils at high doses, and was inactive on neutrophils. MCP-5 induced a calcium flux in peripheral blood mononuclear cells, but not in purified murine eosinophils or neutrophils. Consistent with these results, MCP-5 induced a calcium flux in human embryonic kidney (HEK)-293 cells transfected with human and murine CCR2, a CC chemokine receptor expressed on monocytes. MCP-5 did not induce a calcium flux in HEK-293 cells transfected with CCR1, CCR3, or CCR5. Constitutive expression of MCP-5 mRNA was detected predominantly in lymph nodes, and its expression was markedly induced in macrophages activated in vitro and in vivo. Moreover, MCP-5 expression was up-regulated in the lungs of mice following aerosolized antigen challenge of sensitized mice, and during the host response to infection with Nippostrongylus brasiliensis. These data indicate that MCP-5 is a novel and potent monocyte active chemokine that is involved in allergic inflammation and the host response to pathogens.

Hospital Readmissions to Nonindex Hospitals: Patterns and Determinants Following the Medicare Readmission Reduction Penalty Program.

OBJECTIVE: To examine patterns and determinants of nonindex readmissions for Medicare as well as non-Medicare patients both before and immediately after the adoption of Medicare's Hospital Readmission Reduction Program (HRRP) in 2012. Nonindex readmissions are readmissions to hospitals that are different from the one from which the patient was discharged. METHODS: Observational analysis of statewide database from California comprising patient-level discharge reports. Mixed-effects logistic regression models examined the association between nonindex readmissions and both hospital- and patient-level characteristics. RESULTS: Nonindex readmissions for the population studied were approximately 25%, but the percentage of such readmissions was significantly higher for non-Medicare patients than those enrolled in Medicare. Nonindex readmissions were associated with several patient- and hospital-level characteristics from which patients were discharged. The adoption of the HRRP did not have any appreciable impact on the general pattern of nonindex readmissions. CONCLUSIONS: A substantial percentage of hospital readmissions are to nonindex hospitals, but the general pattern and determinants of these events have not changed following the adoption of the HRRP. As preventable readmissions continue to gain attention as a key quality indicator for hospital care, further investigations are needed to understand the potential value of nonindex readmissions as a quality indicator for hospital care.