Disparities in Tumor Mutational Burden, Immunotherapy Use, and Outcomes Based on Genomic Ancestry in Non-Small-Cell Lung Cancer.

PURPOSE: In patients with advanced non-small-cell lung cancer (aNSCLC), tumor mutational burden (TMB) may vary by genomic ancestry; however, its impact on treatment outcomes is unclear. This retrospective, observational study describes treatment patterns of patients with aNSCLC by genomic ancestry and electronic health record (EHR)-reported race and/or ethnicity and evaluates differences in TMB, cancer immunotherapy (CIT) access, and treatment outcomes across racial and ancestral groups. METHODS: Patients diagnosed with aNSCLC after January 1, 2011, were selected from a real-world deidentified clinicogenomics database and EHR-derived database; continuously enrolled patients were evaluated. Race and/or ethnicity was recorded using variables from the EHR database; genomic ancestry was classified by single-nucleotide polymorphisms on a next-generation sequencing panel. A threshold of 16 mutations per megabase was used to categorize TMB status. RESULTS: Of 59,559 patients in the EHR-derived database and 7,548 patients in the clinicogenomics database, 35,016 (58.8%) and 4,392 (58.2%) were continuously enrolled, respectively. CIT use was similar across EHR-reported race groups, ranging from 34.4% to 37.3% for non-Hispanic Asian and non-Hispanic Black patients, respectively. TMB levels varied significantly across ancestry groups (P < .001); patients of African ancestry had the highest median TMB (8.75 mutations per megabase; interquartile range, 4.35-14.79). In patients who had received CIT, high TMB was associated with improved overall survival compared with low TMB (20.89 v 11.83 months; hazard ratio, 0.60; 95% CI, 0.51 to 0.70) across genomic ancestral groups. CONCLUSION: These results suggest that equitable access to next-generation sequencing may improve aNSCLC outcome disparities in racially and ancestrally diverse populations.

Front-line treatment patterns in multiple myeloma: An analysis of U.S.-based electronic health records from 2011 to 2019.

Multiple myeloma (MM) treatment options have evolved rapidly, but how new agents are incorporated into treatment decisions in current practice is not well understood. This study examined prescribing trends of physicians treating newly diagnosed MM and treatment outcomes in the United States. Electronic health record data from 6271 adult patients diagnosed with MM and receiving initial treatment between 1 January 2011 and 31 January 2020 were derived from the Flatiron Health electronic-health record de-identified database. The number/types of agents included in therapy regimens, time to next treatment (TTNT), and overall survival (OS) were assessed. Subgroups were analyzed by the International Staging System (ISS) disease stage at diagnosis, stem cell transplant eligibility and timing, and practice type. Exploratory prognostic models evaluated the association between baseline covariates and time-to-event outcomes. The proportion of patients receiving triplet therapies increased from 2011 (36%) to 2019 (72%) as those receiving initial monotherapy or doublet therapy decreased. Overall, the most prevalent triplet regimen consisted of an immunomodulatory drug (IMiD), a proteasome inhibitor, and a steroid. From 2017 to 2019, median TTNT from front-line to second-line was longer in patients with ISS stage I versus stages II/III, and in those receiving IMiD-containing doublet or triplet therapies versus other combinations. Overall median OS was 56 months and increased from 2011 to 2014, after which median OS was not yet reached. Age, ISS stage, and high-risk status were prognostic for both OS and TTNT, while sex, practice type, and ECOG status were prognostic for OS only.

Application of a Two-Analyte Integrated Population Pharmacokinetic Model to Evaluate the Impact of Intrinsic and Extrinsic Factors on the Pharmacokinetics of Polatuzumab Vedotin in Patients with Non-Hodgkin Lymphoma.

PURPOSE: The established two-analyte integrated population pharmacokinetic model was applied to assess the impact of intrinsic/extrinsic factors on the pharmacokinetics (PK) of polatuzumab vedotin (pola) in patients with non-Hodgkin lymphoma (NHL) following bodyweight-based dosing. METHODS: Model simulations based on individual empirical Bayes estimates were used to evaluate the impact of intrinsic/extrinsic factors as patient subgroups on Cycle 6 exposures. Intrinsic factors included bodyweight, age, sex, hepatic and renal functions. Extrinsic factors included rituximab/obinutuzumab or bendamustine combination with pola and manufacturing process. The predicted impact on exposures along with the established exposure-response relationships were used to assess clinical relevance. RESULTS: No clinically meaningful differences in Cycle 6 pola exposures were found for the following subgroups: bodyweight 100-146 kg versus 38-<100 kg, age ≥ 65 years versus <65 years, female versus male, mild hepatic impairment versus normal, mild-to-moderate renal impairment versus normal. Co-administration of rituximab/obinutuzumab or bendamustine, and change in the pola manufacturing process, also had no meaningful impact on PK. CONCLUSIONS: In patients with NHL, bodyweight-based dosing is adequate, and no further dose adjustment is recommended for the heavier subgroup (100-146 kg). In addition, no dose adjustments are recommended for other subgroups based on intrinsic/extrinsic factors evaluated.

Determinants of Pediatric Psychiatry Length of Stay in 2 Urban Emergency Departments.

OBJECTIVES: Pediatric mental illness poses a significant burden with an overall prevalence of approximately 10%. Increasingly, children with mental disorders seek care in the emergency department (ED). However, the ED is not an ideal setting. Pediatric mental health patients receive limited treatment and experience significantly longer length of stay (LOS) than other patients seen in the ED. This study examines patient and hospital factors associated with LOS and prolonged LOS (PLOS). METHODS: This is a retrospective chart review of patients between the ages of 3 and 17 presenting at 2 participating urban EDs with a psychiatric diagnosis from May 2010 to May 2012. RESULTS: This study includes 939 patients with an average age of 14.1 years and a median LOS of 295 minutes. The diagnosis was the strongest predictor of LOS and PLOS. Patients with a psychotic disorder or suicide attempt or ideation experienced a longer LOS, 35% and 55% increases, respectively, and an increased odds of PLOS (odds ratio, 3.07 and 8.36, respectively). Patient sex, previous history of self-harm, and the daily census were associated with both a longer LOS and PLOS. Ethnicity, site of admission, and year of admission were only associated with LOS. CONCLUSIONS: Diagnosis-specific management factors are the primary determinant of LOS. However, some patient characteristics and hospital operational factors are also associated with LOS. Organizational reforms and an evaluation of the required human and material resources are necessary to improve access to and availability of pediatric mental health care.

A retrospective analysis of ethnic and gender differences in alcohol consumption among emergency department patients: a cross-sectional study.

BACKGROUND: Previous studies of alcohol use have recognized several trends in consumption patterns among gender and age yet few have examined ethnic differences. This study examines the intra- and inter-ethnic differences in alcohol consumption among a population of patients seen in the emergency department. METHODS: This is a cross-sectional study conducted in the emergency department in a large urban setting. Information on drinking behavior and ethnicity was collected using the Computerized Alcohol Screening and Brief Intervention (CASI) tool. We explored differences in drinking patterns using a multivariate multinomial logistic regression model. RESULTS: We analyzed the drinking habits of 2,444 patients surveyed between November 2012 and May 2014. The results indicate that when compared to non-Hispanic whites, Asians have the lowest odds of drinking within normal limits or excessively, followed by other Latinos, and Mexicans. Age and gender consistently showed statistically significant associations with alcohol-use. The odds of drinking within normal limits or excessively are inversely associated with age and were lower among females. The predicted probabilities show a marked gender-specific difference in alcohol use both between and within ethnic/racial groups. They also highlight an age-related convergence in alcohol use between men and women within ethnic groups. DISCUSSION: The results of this study show intra-racial/ethnic variability associated with sex and education. The highlighted differences within and between ethnic groups reinforce the need to use refined categories when examining alcohol use among minorities. CONCLUSION: The results of this study confirm some alcohol consumption trends among ethnic minorities observed in literature. It provides empirical evidence of the marked gender differences and highlights an age-related convergence for gender-specific alcohol use. Health-care personnel should be aware of these differences when screening and counseling.

Patient Motivators for Emergency Department Utilization: A Pilot Cross-Sectional Survey of Uninsured Admitted Patients at a University Teaching Hospital.

BACKGROUND: During the past several decades, emergency department (ED) increasing volume has proven to be a difficult challenge to address. With the advent of the Affordable Care Act, there is much speculation on the impact that health care coverage expansion will have on ED usage across the country. It is currently unclear what the effects of Medicaid expansion and a decreased number of uninsured patients will have on ED usage. OBJECTIVE: We sought to identify the motivators behind ED use in patients who were admitted to a university teaching hospital in order to project the possible impact of health care reform on ED utilization. METHODS: We surveyed a convenience sample of uninsured patients who presented to the ED and were subsequently admitted to the inpatient setting. RESULTS: Our respondents sought care in the ED primarily because they perceived their condition to be a medical emergency. Their lack of insurance and associated costs of care resulted in delays in seeking care, in reduced access, and a limited ability to manage chronic health conditions. Thus, contributing to their admission. CONCLUSIONS: Affordability will reduce financial barriers to health care insurance coverage. However, efficient and timely access to primary care is a stronger determinant of ED usage in our sample. Health insurance coverage does not guarantee improved health care access. Patients may continue to experience significant challenges in managing chronic health conditions.

Polysubstance abuse: alcohol, opioids and benzodiazepines require coordinated engagement by society, patients, and physicians.

The Centers for Disease Control and Prevention (CDC) has published significant data trends related to substance abuse involving opioid pain relievers (OPR), benzodiazepines and alcohol in the United States. The CDC describes opioid misuse and abuse as an epidemic, with the use of OPR surpassing that of illicit drugs. Alcohol has also been a persistent problem and is associated with a number of emergency department visits and deaths independent of other substances. The use of these drugs in combination creates an additive effect with increased central nervous system suppression and a heightened risk of an overdose. We present a summary of the findings from the Morbidity and Mortality Weekly Report (MMWR) with commentary on strategies to combat prescription drug and alcohol abuse.

Using quality measures for quality improvement: the perspective of hospital staff.

RESEARCH OBJECTIVE: This study examines the perspectives of a range of key hospital staff on the use, importance, scientific background, availability of data, feasibility of data collection, cost benefit aspects and availability of professional personnel for measurement of quality indicators among Iranian hospitals. The study aims to facilitate the use of quality indicators to improve quality of care in hospitals. STUDY DESIGN: A cross-sectional study was conducted over the period 2009 to 2010. Staff at Iranian hospitals completed a self-administered questionnaire eliciting their views on organizational, clinical process, and outcome (clinical effectiveness, patient safety and patient centeredness) indicators. POPULATION STUDIED: 93 hospital frontline staff including hospital/nursing managers, medical doctors, nurses, and quality improvement/medical records officers in 48 general and specialized hospitals in Iran. PRINCIPAL FINDINGS: On average, only 69% of respondents reported using quality indicators in practice at their affiliated hospitals. Respondents varied significantly in their reported use of organizational, clinical process and outcome quality indicators. Overall, clinical process and effectiveness indicators were reported to be least used. The reported use of indicators corresponded with their perceived level of importance. Quality indicators were reported to be used among clinical staff significantly more than among managerial staff. In total, 74% of the respondents reported to use obligatory indicators, while this was 68% for voluntary indicators (p<0.05). CONCLUSIONS: There is a general awareness of the importance and usability of quality indicators among hospital staff in Iran, but their use is currently mostly directed towards external accountability purposes. To increase the formative use of quality indicators, creation of a common culture and feeling of shared ownership, alongside an increased uptake of clinical process and effectiveness indicators is needed to support internal quality improvement processes at hospital level.

Regulating Quality and Safety of Health and Social Care: International Experiences.

This study is concerned with "standards of quality and safety" within health and social care systems. Care standards are intended to support efforts in maintaining and improving the quality of care; they have been developed across countries, although the ways in which they are implemented and applied differs between nations. Taking a range of six countries, we review the regulatory mechanisms that have been implemented to ensure that essential standards of care are applied and are being adhered to, and consider the range of policy instruments used to encourage and ensure continuous quality improvement. We report on Australia, England, Finland, Germany, the Netherlands and the USA. The study is intended to inform policy thinking for the Department of Health and others in developing the regulation of safety and quality of health and social care in England. It was prepared as part of the project "An 'On-call' Facility for International Healthcare Comparisons" funded by the Department of Health in England through its Policy Research Programme.

Effects of hospital delivery during off-hours on perinatal outcome in several subgroups: a retrospective cohort study.

BACKGROUND: Studies have demonstrated a higher risk of adverse outcomes among infants born or admitted during off-hours, as compared to office hours, leading to questions about quality of care provide during off-hours (weekend, evening or night). We aim to determine the relationship between off-hours delivery and adverse perinatal outcomes for subgroups of hospital births. METHODS: This retrospective cohort study was based on data from the Netherlands Perinatal Registry, a countrywide registry that covers 99% of all hospital births in the Netherlands. Data of 449,714 infants, born at 28 completed weeks or later, in the period 2003 through 2007 were used. Infants with a high a priori risk of morbidity or mortality were excluded. Outcome measures were intrapartum and early neonatal mortality, a low Apgar score (5 minute score of 0-6), and a composite adverse perinatal outcome measure (mortality, low Apgar score, severe birth trauma, admission to a neonatal intensive care unit). RESULTS: Evening and night-time deliveries that involved induction or augmentation of labour, or an emergency caesarean section, were associated with an increased risk of an adverse perinatal outcome when compared to similar daytime deliveries. Weekend deliveries were not associated with an increased risk when compared to weekday deliveries. It was estimated that each year, between 126 and 141 cases with an adverse perinatal outcomes could be attributed to this evening and night effect. Of these, 21 (15-16%) are intrapartum or early neonatal death. Among the 3100 infants in the study population who experience an adverse outcome each year, death accounted for only 5% (165) of these outcomes. CONCLUSION: This study shows that for infants whose mothers require obstetric interventions during labour and delivery, birth in the evening or at night, are at an increased risk of an adverse perinatal outcomes.

A multifaceted look at time of admission and its impact on case-fatality among a cohort of ischaemic stroke patients.

PURPOSE: Off-hours admissions have been associated with an increased risk of poor outcomes but results have been inconsistent, possibly due to different measures of off-hours care used. We examined, using a single condition and increasingly refined definitions of time of admission, the effect of off-hours admissions on 7-day stroke case-fatality. METHODS: We studied a retrospective cohort of 82,219 ischaemic stroke admissions to 115 Dutch hospitals between 2000 and 2004. Data were from the Dutch Medical Register and analysed using multivariable multilevel logistic regression. We adjusted for variables such as age, gender, Charlson-Deyo comorbidity score, urgency of admission, hospital teaching status and speciality of attending physician. RESULTS: After adjustment, we observed higher 7-day death risk for weekend admissions when compared to weekday admissions (OR 1.27; 95% CI 1.20 to 1.34). Sunday displayed the highest risk of death (OR 1.31; 95% CI 1.20 to 1.44). With the Monday day-shift as a reference, the death odds were increased during the Sunday and Saturday day-shifts, the evening-shifts on Sunday and Monday, and during all night-shifts. The night-shift ORs ranged from 1.94 (95% CI 1.56 to 2.41) to 2.14 (95% CI 1.74 to 2.63). When compared to admission at 8:00 we observed increased death odds from midnight until 7:00 and decreased death odds from 14:00 until 18:00. CONCLUSIONS: Weekends represent a period of increased death risk for ischaemic stroke patients in the Netherlands. However, this increased risk appears to represent an exacerbation of an underlying night-time risk present during the weekdays.

Hospital stroke volume and case-fatality revisited.

BACKGROUND: A few studies have found an inverse association between hospital patient volume and case-fatality among stroke patients. However, the different stroke categorizations used in these studies might have influenced the findings. Furthermore, the relevance of the association observed remains questionable given that the relatively small magnitude may not support volume-based referral policies. We re-examined this association in a large nationwide study, paying attention to the influence of volume categorizations. METHODS: Applying multilevel logistic regression, we re-examined the relationship between hospital stroke volume and 7-day case-fatality using admissions data obtained from Statistics Netherlands on 73,077 stroke patients for the years 2000 to 2004. Different cut-offs were used to categorize hospitals in volume groups. We also examined the implications of a volume based referral strategy. RESULTS: Stroke patients in high-volume hospitals had decreased risk of dying within 7 days of admission even when different hospital categorizations are applied. For instance, the odds ratio was 0.45(95% CI 0.20-0.99) in high-volume(>200 case-volume) versus low-volume(<50 case-volume) hospitals, but 0.89(95% CI 0.79-1.00) in high-volume(>250 case-volume) versus low-volume (< or =250 case-volume) hospitals. Ignoring travel time and workload implications an optimistic volume-based referral policy would save 183 patients when all patients are referred to the >200 case-volume hospital. A nontransfer policy aimed at reducing mortality by 10% in all those hospitals would save 1260 patients. CONCLUSION: Stroke patients in low-volume versus high-volume hospitals have higher odds of dying. This finding may not lend itself to a substantial volume-based referral strategy.

Too poor to leave, too rich to stay: developmental and global health correlates of physician migration to the United States, Canada, Australia, and the United kingdom.

OBJECTIVES: We analyzed the relationship between physician migration from developing source countries to more developed host countries (brain drain) and the developmental and global health profiles of source countries. METHODS: We used a cross-section of 141 countries that lost emigrating physicians to the 4 major destinations: the United States, Canada, Australia, and the United Kingdom. For each source country, we defined physician migration density as the number of migrant physicians per 1000 population practicing in any of the 4 major destination countries. RESULTS: Source countries with better human resources for health, more economic and developmental progress, and better health status appear to lose proportionately more physicians than the more disadvantaged countries. Higher physician migration density is associated with higher current physician (r=0.42, P< .001), nurse (r=0.27, P=.001), and public health (r=0.48, P=.001) workforce densities and more medical schools (r=0.53, P<.001). CONCLUSIONS: Policymakers should realize that physician migration is positively related to better health systems and development in source countries. In view of the "train, retain, and sustain" perspective of public health workforce policies, physician retention should become even more important to countries growing richer, whereas poorer countries must invest more in training policies.