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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Community Benefit Spending By Tax-Exempt Hospitals Changed Little After ACA.

Provisions of the Affordable Care Act (ACA) encouraged tax-exempt hospitals to invest broadly in community health benefits. Four years after the ACA's enactment, hospitals had increased their average spending for all community benefits by 0.5 percentage point, from 7.6 percent of their operating expenses in 2010 to 8.1 percent in 2014.

Usual Course of Treatment and Predictors of Treatment Utilization for Patients With Posttraumatic Stress Disorder.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is a debilitating psychiatric illness that frequently remains undiagnosed and untreated. While extensive research has been conducted among veterans, little research has evaluated course of treatment for PTSD in a general hospital setting. METHODS: We utilized data from the Partners HealthCare Research Patient Data Registry to evaluate mental health treatment utilization, including psychotherapy and pharmacotherapy, by patients with recently diagnosed primary PTSD following DSM-IV criteria between January 1, 2002, and June 30, 2011. We additionally evaluated predictors of treatment utilization 6 months postdiagnosis. RESULTS: Among 2,475 patients with recently diagnosed primary PTSD, approximately half (55.7%) had any therapy visit and 10% had at least 12 therapy visits in the 6 months following diagnosis. Approximately half (47.0%) received a psychiatric prescription, with 29.3% receiving a selective serotonin reuptake inhibitor (SSRI), 11.8% receiving an atypical antipsychotic, and 24.4% receiving a benzodiazepine. Latinos were 25% (95% CL = 1.09, 1.43) more likely to have an SSRI prescription, 35% (95% CL = 1.05, 1.75) more likely to have an atypical antipsychotic prescription, and 28% (95% CL = 1.19, 1.38) more likely to receive any psychotherapy. Women were 49% (95% CL = 0.42, 0.63) less likely to have an atypical antipsychotic prescription. Patients with Medicare were 23% (95% CL = 0.67, 0.88) less likely to have any psychotherapy, and patients with Medicaid were 35% (95% CL = 0.46, 0.92) less likely to have 12 or more therapy visits. CONCLUSIONS: Many patients with a primary diagnosis of PTSD do not receive psychotherapy, and psychiatric prescriptions, including atypical antipsychotics and benzodiazepines, are common. Future research is needed to determine the quality of care received and explore subpopulation-specific barriers limiting access to care.

Residential segregation and mental health among Latinos in a nationally representative survey.

BACKGROUND: Among Latinos, living in a locality with greater Latino ethnic density may be protective for mental health, although findings vary by Latino subgroup, gender and birthplace. Although little studied, Latino residential segregation may capture different pathways linking risk and protective environmental factors to mental health than local ethnic density. METHODS: This study evaluated the association between residential segregation and mental distress as measured by the Kessler-10 (K10) among Latino participants in the National Latino and Asian American Study (NLAAS). Census data from 2000 was used to calculate metropolitan statistical area (MSA) residential segregation using the dissimilarity and isolation indices, as well as census tract ethnicity density and poverty. Latino subgroup (Puerto Rican, Mexican American, Cuban American and other Latino subgroup), gender and generation status were evaluated as moderators. RESULTS: Among 2554 Latino participants in NLAAS, residential segregation as measured by the isolation index was associated with less mental distress (ß -0.14, 95% CI -0.26 to -0.03 log(K10)) among Latinos overall after adjustment for ethnic density, poverty and individual covariates. Residential segregation as measured by the dissimilarity index was significantly associated with less mental distress among men (ß -0.56, 95% CI -1.04 to -0.08) but not among women (ß -0.20, 95% CI -0.45 to 0.04, p-interaction=0.019). No modification was observed by Latino subgroup or generation. CONCLUSIONS: Among Latinos, increasing residential segregation was associated with less mental distress, and this association was moderated by gender. Findings suggest that MSA-level segregation measures may capture protective effects associated with living in Latino communities for mental health.

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.

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.

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.

A CCL chemokine-derived peptide (CDIP-2) exerts anti-inflammatory activity via CCR1, CCR2 and CCR3 chemokine receptors: Implications as a potential therapeutic treatment of asthma.

Allergic asthma is a chronic inflammatory disease characterized by the accumulation of eosinophils, Th2 cells and mononuclear cells in the airways, leading to changes in lung architecture and subsequently reduced respiratory function. We have previously demonstrated that CDIP-2, a chemokine derived peptide, reduced in vitro chemotaxis and decreased cellular infiltration in a murine model of allergic airway inflammation. However, the mechanisms involved in this process have not been identified yet. Now, we found that CDIP-2 reduces chemokine-mediated functions via interactions with CCR1, CCR2 and CCR3. Moreover, using bone marrow-derived eosinophils, we demonstrated that CDIP-2 modifies the calcium fluxes induced by CCL11 and down-modulated CCR3 expression. Finally, CDIP-2 treatment in a murine model of OVA-induced allergic airway inflammation reduced leukocyte recruitment and decreases production of cytokines. These data suggest that chemokine-derived peptides represent new therapeutic tools to generate more effective antiinflammatory drugs.

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.

CCR9+ T cells contribute to the resolution of the inflammatory response in a mouse model of intestinal amoebiasis.

Analysis of the mechanisms underlying the inflammatory response in amoebiasis is important to understand the immunopathology of the disease. Mucosal associated effector and regulatory T cells may play a role in regulating the inflammatory immune response associated to Entamoeba histolytica infection in the colon. A subpopulation of regulatory T cells has recently been identified and is characterized by the expression of the chemokine receptor CCR9. In this report, we used CCR9 deficient (CCR9(-/-)) mice to investigate the role of the CCR9(+) T cells in a murine model of E. histolytica intestinal infection. Intracecal infection of CCR9(+/+), CCR9(+/-) and CCR9(-/-) mice with E. histolytica trophozoites, revealed striking differences in the development and nature of the intestinal inflammatory response observed between these strains. While CCR9(+/+) and CCR9(+/-) mice were resistant to the infection and resolved the pathogen-induced inflammatory response, CCR9(-/-) mice developed a chronic inflammatory response, which was associated with over-expression of the cytokines IFN-γ, TNF-α, IL-4, IL-6 and IL-17, while IL-10 was not present. In addition, increased levels of CCL11, CCL20 and CCL28 chemokines were detected by qRT-PCR in CCR9(-/-) mice. E. histolytica trophozoites were identified in the lumen of the cecum of CCR9(-/-) mice at seven days post infection (pi), whereas in CCR9(+/+) mice trophozoites disappeared by day 1 pi. Interestingly, the inflammation observed in CCR9(-/-) mice, was associated with a delayed recruitment of CD4(+)CD25(+)FoxP3(+) T cells to the cecal epithelium and lamina propria, suggesting that this population may play a role in the early regulation of the inflammatory response against E. histolytica, likely through IL-10 production. In support of these data, CCR9(+) T cells were also identified in colon tissue sections obtained from patients with amoebic colitis. Our data suggest that a population of CCR9(+)CD4(+)CD25(+)FoxP3(+) T cells may participate in the control and resolution of the inflammatory immune response to E. histolytica infection.