Sex-specific associations between habitual snoring and cancer prevalence: insights from a US Cohort Study.

Study Objectives: To investigate the sex-specific association between habitual snoring and overall cancer prevalence and subtypes, and to examine the influence of age, body mass index (BMI), and sleep duration on this association. Methods: This study utilized data from the National Health and Nutrition Examination Survey cycles between 2005 and 2020 and included 15 892 participants aged 18 and over. We employed inverse probability of treatment weighting based on propensity scores to adjust for confounders when comparing the prevalence of cancer between habitual snorers and non-habitual snorers for each sex and cancer type. Subgroup analyses were conducted based on sleep duration, age, and BMI categories. Results: The cohort (mean age 48.2 years, 50.4% female, and 30.5% habitual snorers) reported 1385 cancer cases. In men, habitual snoring was linked to 26% lower odds of any cancer (OR 0.74, 95% CI: 0.66 to 0.83), while in women, it showed no significant difference except lower odds of breast cancer (OR 0.77, 95% CI: 0.63 to 0.94) and higher odds of cervix cancer (OR 1.54, 95% CI: 1.18 to 2.01). Age and sleep duration significantly influenced the snoring-cancer relationship, with notable variations by cancer type and sex. Conclusions: Habitual snoring exhibits sex-specific associations with cancer prevalence, showing lower prevalence in men and varied results in women. These findings emphasize the critical need for further research to uncover the biological mechanisms involved. Future investigations should consider integrating sleep characteristics with cancer prevention and screening strategies, focusing on longitudinal research and the integration of genetic and biomarker analyses to fully understand these complex relationships.

Multilevel Implementation Strategies for Adolescent Human Papillomavirus Vaccine Uptake: A Cluster Randomized Clinical Trial.

Importance: Despite availability of a safe and effective vaccine, an estimated 36 500 new cancers in the US result from human papillomavirus (HPV) annually. HPV vaccine uptake falls short of national public health goals and lags other adolescent vaccines. Objective: To evaluate the individual and combined impact of 2 evidence-based interventions on HPV vaccination rates among 11- and 12-year-old children. Design, Setting, and Participants: The study team conducted a cluster randomized clinical trial with a stepped-wedge factorial design at 6 primary care practices affiliated with Mayo Clinic in southeastern Minnesota. Using block randomization to ensure balance of patient volumes across interventions, each practice was allocated to a sequence of four 12-month steps with the initial baseline step followed by 2 intermediate steps (none, 1, or both interventions) and a final step wherein all practices implemented both interventions. Each month, all eligible children who turned 11 or 12 years in the 2 months prior were identified and followed until the end of the step. Data were analyzed from April 2018 through March 2019. Participants included children who turned 11 or 12 years old and were due for a dose of the HPV vaccine. Interventions: Parents of eligible patients were mailed reminder/recalls following their child's birthdays. Health care professionals received confidential audit/feedback on their personal in-office success with HPV vaccine uptake via intra-campus mail. These 2 interventions were assessed separately and in combination. Main Outcomes and Measures: Eligible patients' receipt of any valid dose of HPV vaccine during the study step. Results: The cohort was comprised of 9242 11-year-olds (5165 [55.9%]) and 12-year-olds (4077 [44.1%]), and slightly more males (4848 [52.5%]). Parent reminder/recall resulted in 34.6% receiving a dose of HPV vaccine, health care professional audit/feedback, 30.4%, both interventions together resulted in 39.7%-all contrasted to usual care, 21.9%. Compared with usual care, the odds of HPV vaccination were higher for parent reminder/recall (odds ratio [OR], 1.56; 95% CI, 1.23-1.97) and for the combination of parent reminder/recall and health care professional audit/feedback (OR, 2.03; 95% CI, 1.44-2.85). Health care professional audit/feedback alone did not differ significantly from usual care (OR, 1.19; 95% CI, 0.94-1.51). Conclusions and Relevance: In this cluster randomized trial, the combination of parent reminder/recall and health care professional audit/feedback increased the odds of HPV vaccination compared with usual care. These findings underscore the value of simultaneous implementation of evidence-based strategies to improve HPV vaccination.

Uncovering heterogeneous cardiometabolic risk profiles in US adults: the role of social and behavioral determinants of health.

INTRODUCTION: Social and behavioral determinants of health (SBDH) have been linked to diabetes risk, but their role in explaining variations in cardiometabolic risk across race/ethnicity in US adults is unclear. This study aimed to classify adults into distinct cardiometabolic risk subgroups using SBDH and clinically measured metabolic risk factors, while comparing their associations with undiagnosed diabetes and pre-diabetes by race/ethnicity. RESEARCH DESIGN AND METHODS: We analyzed data from 38,476 US adults without prior diabetes diagnosis from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. The k-prototypes clustering algorithm was used to identify subgroups based on 16 SBDH and 13 metabolic risk factors. Each participant was classified as having no diabetes, pre-diabetes or undiagnosed diabetes using contemporaneous laboratory data. Logistic regression was used to assess associations between subgroups and diabetes status, focusing on differences by race/ethnicity. RESULTS: Three subgroups were identified: cluster 1, primarily middle-aged adults with high rates of smoking, alcohol use, short sleep duration, and low diet quality; cluster 2, mostly young non-white adults with low income, low health insurance coverage, and limited healthcare access; and cluster 3, mostly older males who were the least physically active, but with high insurance coverage and healthcare access. Compared with cluster 2, adjusted ORs (95% CI) for undiagnosed diabetes were 14.9 (10.9, 20.2) in cluster 3 and 3.7 (2.8, 4.8) in cluster 1. Clusters 1 and 3 (vs cluster 2) had high odds of pre-diabetes, with ORs of 1.8 (1.6, 1.9) and 2.1 (1.8, 2.4), respectively. Race/ethnicity was found to modify the relationship between identified subgroups and pre-diabetes risk. CONCLUSIONS: Self-reported SBDH combined with metabolic factors can be used to classify adults into subgroups with distinct cardiometabolic risk profiles. This approach may help identify individuals who would benefit from screening for diabetes and pre-diabetes and potentially suggest effective prevention strategies.

Association of Population Well-Being With Cardiovascular Outcomes.

Importance: Mortality from cardiovascular disease (CVD) varies across communities and is associated with known structural and population health factors. Still, a population's well-being, including sense of purpose, social relationships, financial security, and relationship to community, may be an important target to improve cardiovascular health. Objective: To examine the association of population level measures of well-being with rates of CVD mortality in the US. Design, Setting, and Participants: This cross-sectional study linked data from the Gallup National Health and Well-Being Index (WBI) survey to county-level rates of CVD mortality from the Centers for Disease Control and Prevention Atlas of Heart Disease and Stroke. Participants were respondents of the WBI survey, which was conducted by Gallup with randomly selected adults aged 18 years or older from 2015 to 2017. Data were analyzed from August 2022 to May 2023. Main Outcomes and Measures: The primary outcome was the county-level rate of total CVD mortality; secondary outcomes were mortality rates for stroke, heart failure, coronary heart disease, acute myocardial infarction, and total heart disease. The association of population well-being (measured using a modified version of the WBI) with CVD mortality was assessed, and an analysis of whether the association was modified by county structural factors (Area Deprivation Index [ADI], income inequality, and urbanicity) and population health factors (percentages of the adult population who had hypertension, diabetes, or obesity; were currently smoking; and were physically inactive) was conducted. Population WBI and its ability to mediate the association of structural factors associated with CVD using structural equation models was also assessed. Results: Well-being surveys were completed by 514 971 individuals (mean [SD] age 54.0 [19.2] years; 251 691 [48.9%] women; 379 521 [76.0%] White respondents) living in 3228 counties. Mortality rates for CVD decreased from a mean of 499.7 (range, 174.2-974.7) deaths per 100 000 persons in counties with the lowest quintile of population well-being to 438.6 (range, 110.1-850.4) deaths per 100 000 persons in counties with the highest quintile of population well-being. Secondary outcomes showed similar patterns. In the unadjusted model, the effect size (SE) of WBI on CVD mortality was -15.5 (1.5; P < .001), or a decrease of 15 deaths per 100 000 persons for each 1-point increase of population well-being. After adjusting for structural factors and structural plus population health factors, the association was attenuated but still significant, with an effect size (SE) of -7.3 (1.6; P < .001); for each 1-point increase in well-being, the total cardiovascular death rate decreased by 7.3 deaths per 100 000 persons. Secondary outcomes showed similar patterns, with mortality due to coronary heart disease and heart failure being significant in fully adjusted models. In mediation analyses, associations of income inequality and ADI with CVD mortality were all partly mediated by the modified population WBI. Conclusions and Relevance: In this cross-sectional study assessing the association of well-being and cardiovascular outcomes, higher well-being, a measurable, modifiable, and meaningful outcome, was associated with lower CVD mortality, even after controlling for structural and cardiovascular-related population health factors, indicating that well-being may be a focus for advancing cardiovascular health.

Prevalence, Severity, and Co-Occurrence of SPPADE Symptoms in 31,866 Patients With Cancer.

OBJECTIVES: To examine the prevalence, severity, and co-occurrence of SPPADE symptoms as well as their association with cancer type and patient characteristics. BACKGROUND: The SPPADE symptoms (sleep disturbance, pain, physical function impairment, anxiety, depression, and low energy /fatigue) are prevalent, co-occurring, and undertreated in oncology and other clinical populations. METHODS: Baseline SPPADE symptom data were analyzed from the E2C2 study, a stepped wedge pragmatic, population-level, cluster randomized clinical trial designed to evaluate a guideline-informed symptom management model targeting the six SPPADE symptoms. Symptom prevalence and severity were measured with a 0-10 numeric rating (NRS) scale for each of the six symptoms. Prevalence of severe (NRS ≥ 7) and potential clinically relevant (NRS ≥ 5) symptoms as well as co-occurrence of clinical symptoms were determined. Distribution-based methods were used to estimate the minimally important difference (MID). Associations of cancer type and patient characteristics with a SPPADE composite score were analyzed. RESULTS: A total of 31,886 patients were assessed for SPPADE symptoms prior to, during, or soon after an outpatient medical oncology encounter. The proportion of patients with a potential clinically relevant symptom ranged from 17.5% for depression to 33.4% for fatigue. Co-occurrence of symptoms was high, with the proportion of patients with three or more additional clinically relevant symptoms ranging from 45.2% for fatigue to 68.6% for depression. The summed SPPADE composite score demonstrated good internal reliability (Cronbach's alpha of 0.86), with preliminary MID estimates of 4.1-4.3. Symptom burden differed across several types of cancer but was generally similar across most sociodemographic characteristics. CONCLUSION: The high prevalence and co-occurrence of SPPADE symptoms in patients with all types of cancer warrants clinical approaches that optimize detection and management.

Pragmatic cluster randomized trial to evaluate effectiveness and implementation of EHR-facilitated collaborative symptom control in cancer (E2C2): addendum.

We previously described the hypotheses, outcomes, design, and analysis for E2C2, a pragmatic stepped-wedge trial to assess an intervention to improve symptom control in patients with cancer. Subsequent consideration of the design and cohort led to the addition of a second primary hypothesis. This article describes and presents the rationale for this second hypothesis. This addendum also details a revised analytic approach, necessitated by inconsistencies in the original analytic plan. The design, outcomes, and other aspects of the protocol remain unchanged.

Perioperative magnetic resonance imaging in breast cancer care: Distinct adoption trajectories among physician patient-sharing networks.

BACKGROUND: Despite no proven benefit in clinical outcomes, perioperative magnetic resonance imaging (MRI) was rapidly adopted into breast cancer care in the 2000's, offering a prime opportunity for assessing factors influencing overutilization of unproven technology. OBJECTIVES: To examine variation among physician patient-sharing networks in their trajectory of adopting perioperative MRI for breast cancer surgery and compare the characteristics of patients, providers, and mastectomy use in physician networks that had different adoption trajectories. METHODS AND FINDINGS: Using the Surveillance, Epidemiology, and End Results-Medicare database in 2004-2009, we identified 147 physician patient-sharing networks (caring for 26,886 patients with stage I-III breast cancer). After adjusting for patient clinical risk factors, we calculated risk-adjusted rate of perioperative MRI use for each physician network in 2004-2005, 2006-2007, and 2008-2009, respectively. Based on the risk-adjusted rate, we identified three distinct trajectories of adopting perioperative MRI among physician networks: 1) low adoption (risk-adjusted rate of perioperative MRI increased from 2.8% in 2004-2005 to 14.8% in 2008-2009), 2) medium adoption (8.8% to 45.1%), and 3) high adoption (33.0% to 71.7%). Physician networks in the higher adoption trajectory tended to have a larger proportion of cancer specialists, more patients with high income, and fewer patients who were Black. After adjusting for patients' clinical risk factors, the proportion of patients undergoing mastectomy decreased from 41.1% in 2004-2005 to 38.5% in 2008-2009 among those in physician networks with low MRI adoption, but increased from 27.0% to 31.4% among those in physician networks with high MRI adoption (p = 0.03 for the interaction term between trajectory group and time). CONCLUSIONS: Physician patient-sharing networks varied in their trajectory of adopting perioperative MRI. These distinct trajectories were associated with the composition of patients and providers in the networks, and had important implications for patterns of mastectomy use.

A Clinical Decision Aid to Support Personalized Treatment Selection for Patients with Clinical T1 Renal Masses: Results from a Multi-institutional Competing-risks Analysis.

BACKGROUND: Personalized treatment for clinical T1 renal cortical masses (RCMs) should take into account competing risks related to tumor and patient characteristics. OBJECTIVE: To develop treatment-specific prediction models for cancer-specific mortality (CSM), other-cause mortality (OCM), and 90-d Clavien grade ≥3 complications across radical nephrectomy (RN), partial nephrectomy (PN), thermal ablation (TA), and active surveillance (AS). DESIGN, SETTING, AND PARTICIPANTS: Pretreatment clinical and radiological features were collected for consecutive adult patients treated with initial RN, PN, TA, or AS for RCMs at four high-volume referral centers (2000-2019). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Prediction models used competing-risks regression for CSM and OCM and logistic regression for 90-d Clavien grade ≥3 complications. Performance was assessed using bootstrap validation. RESULTS AND LIMITATIONS: The cohort comprised 5300 patients treated with RN (n = 1277), PN (n = 2967), TA (n = 476), or AS (n = 580). Over median follow-up of 5.2 yr (interquartile range 2.5-8.7), there were 117 CSM, 607 OCM, and 198 complication events. The C index for the predictive models was 0.80 for CSM, 0.77 for OCM, and 0.64 for complications. Predictions from the fitted models are provided in an online calculator (https://small-renal-mass-risk-calculator.fredhutch.org). To illustrate, a hypothetical 74-yr-old male with a 4.5-cm RCM, body mass index of 32 kg/m2, estimated glomerular filtration rate of 50 ml/min, Eastern Cooperative Oncology Group performance status of 3, and Charlson comorbidity index of 3 has predicted 5-yr CSM of 2.9-5.6% across treatments, but 5-yr OCM of 29% and risk of 90-d Clavien grade 3-5 complications of 1.9% for RN, 5.8% for PN, and 3.6% for TA. Limitations include selection bias, heterogeneity in practice across treatment sites and the study time period, and lack of control for surgeon/hospital volume. CONCLUSIONS: We present a risk calculator incorporating pretreatment features to estimate treatment-specific competing risks of mortality and complications for use during shared decision-making and personalized treatment selection for RCMs. PATIENT SUMMARY: We present a risk calculator that generates personalized estimates of the risks of death from cancer or other causes and of complications for surgical, ablation, and surveillance treatment options for patients with stage 1 kidney tumors.

Receptivity to a Nurse-Led Symptom Management Intervention Among Highly Symptomatic Patients With Cancer.

BACKGROUND: The symptom burden associated with cancer and its treatment can negatively affect patients' quality of life and survival. Symptom-focused collaborative care model (CCM) interventions can improve outcomes, but only if patients engage with them. We assessed the receptivity of severely symptomatic oncology patients to a remote nurse-led CCM intervention. METHODS: In a pragmatic, cluster-randomized, stepped-wedge trial conducted as part of the National Cancer Institute IMPACT Consortium (E2C2, NCT03892967), patients receiving cancer care were asked to rate their sleep disturbance, pain, anxiety, emotional distress, fatigue, and limitations in physical function. Patients reporting at least 1 severe symptom (≥7/10) were offered phone consultation with a nurse symptom care manager (RN SCM). Initially, patients had to "opt-in" to receive a call, but the protocol was later modified so they had to "opt-out" if they did not want a call. We assessed the impact of opt-in vs opt-out framing and patient characteristics on receptiveness to RN SCM calls. All statistical tests were 2-sided. RESULTS: Of the 1204 symptom assessments (from 864 patients) on which at least 1 severe symptom was documented, 469 (39.0%) indicated receptivity to an RN SCM phone call. The opt-out period (odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.12 to 2.32, P = .01), receiving care at a tertiary care center (OR = 3.59, 95% CI = 2.18 to 5.91, P < .001), and having severe pain (OR = 1.80, 95% CI = 1.24 to 2.62, P = .002) were associated with statistically significantly greater willingness to receive a call. CONCLUSIONS: Many severely symptomatic patients were not receptive to an RN SCM phone call. Better understanding of reasons for refusal and strategies for improving patient receptivity are needed.

Comparative Risk of Serious Infections With Tumor Necrosis Factor α Antagonists vs Vedolizumab in Patients With Inflammatory Bowel Diseases.

BACKGROUND AND AIMS: We conducted a retrospective cohort study comparing the risk of serious infections between patients treated with tumor necrosis factor-a (TNFa) antagonists vs. vedolizumab in patients with inflammatory bowel diseases (IBD). METHODS: Using an administrative claims database, we identified patients with IBD who were new-users of either TNFa antagonists or vedolizumab between 2014-2018 and had insurance coverage for at least 1y before and after treatment initiation. We compared the risk of serious infections (infections requiring hospitalization) between patients treated with vedolizumab or TNFa antagonists using marginal structural Cox proportional hazard models adjusted for baseline disease characteristics, healthcare utilization, comorbidities, and time-varying use of corticosteroids, immunomodulators and opiates. RESULTS: We included 4881 patients treated with TNFa antagonists (age, 41 ± 15y, 60% with Crohn's disease [CD]) of whom 434 developed serious infections over 5786 person-year [PY] follow-up, and 1106 patients treated with vedolizumab (age, 44 ± 16y, 39% with CD) of whom 86 developed serious infections over 1040-PY follow-up. Vedolizumab was associated with 46% lower risk of serious infections as compared with TNFa antagonists in patients with ulcerative colitis (HR,0.54 [95% CI,0.35-0.83), but no significant differences were observed in patients with CD (HR,1.30 [0.80-2.11]). Vedolizumab was associated with lower risk of extra-intestinal serious infections in patients with UC, but higher risk of gastrointestinal serious infections in patients with CD. CONCLUSIONS: In an observational study of patients with IBD, vedolizumab was associated with lower risk of serious infections as compared with TNFa antagonists, in patients with UC, but not in patients with CD.

Real-world Cardiovascular Outcomes Associated With Degarelix vs Leuprolide for Prostate Cancer Treatment.

Importance: With a growing interest in the use of real-world evidence for regulatory decision-making, it is important to understand whether real-world data can be used to emulate the results of randomized clinical trials. Objective: To use electronic health record and administrative claims data to emulate the ongoing PRONOUNCE trial (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease). Design, Setting, and Participants: This retrospective, propensity-matched cohort study included adult men with a diagnosis of prostate cancer and cardiovascular disease who initiated either degarelix or leuprolide between December 24, 2008, and June 30, 2019. Participants were commercially insured individuals and Medicare Advantage beneficiaries included in a large US administrative claims database. Exposures: Degarelix or leuprolide. Main Outcomes and Measures: The primary end point was time to first occurrence of a major adverse cardiovascular event (MACE), defined as death due to any cause, myocardial infarction, or stroke, analogous to the PRONOUNCE trial. Secondary end points were time to death due to any cause, myocardial infarction, stroke, and angina. Cox proportional hazards regression was used to evaluate primary and secondary end points. Results: A total of 32 172 men initiated degarelix or leuprolide for prostate cancer; of them, 9490 (29.5%) had cardiovascular disease, and 7800 (24.2%) met the PRONOUNCE trial eligibility criteria and were included in this study. Overall, 165 participants (2.1%) were Asian, 1390 (17.8%) were Black, 663 (8.5%) were Hispanic, and 5258 (67.4%) were White. The mean (SD) age was 74.4 (7.4) years. Among 2226 propensity score-matched patients, no significant difference was observed in the risk of MACE for patients taking degarelix vs those taking leuprolide (10.18 vs 8.60 events per 100 person-years; hazard ratio [HR], 1.18; 95% CI, 0.86-1.61). Degarelix was associated with a higher risk of death from any cause (HR, 1.48; 95% CI, 1.01-2.18) but not of myocardial infarction (HR, 1.16; 95% CI, 0.60-2.25), stroke (HR, 0.92; 95% CI, 0.45-1.85), or angina (HR, 1.36; 95% CI, 0.43-4.27). Conclusions and Relevance: In this emulation of a clinical trial of men with cardiovascular disease undergoing treatment for prostate cancer, degarelix was not associated with a lower risk of cardiovascular events than leuprolide. Comparison of these data with PRONOUNCE trial results, when published, will help enhance our understanding of the appropriate role of using real-world data to emulate clinical trials.

Uptake of evidence by physicians: De-adoption of erythropoiesis-stimulating agents after the TREAT trial.

BACKGROUND: Variation in de-adoption of ineffective or unsafe treatments is not well-understood. We examined de-adoption of erythropoiesis-stimulating agents (ESA) in anemia treatment among patients with chronic kidney disease (CKD) following new clinical evidence of harm and ineffectiveness (the TREAT trial) and the FDA's revision of its safety warning. METHOD: We used a segmented regression approach to estimate changes in use of epoetin alfa (EPO) and darbepoetin alfa (DPO) in the commercial, Medicare Advantage (MA) and Medicare fee-for-service (FFS) populations. We also examined how changes in both trends and levels of use were associated with physicians' characteristics. RESULTS: Use of DPO and EPO declined over the study period. There were no consistent changes in DPO trend across insurance groups, but the level of DPO use decreased right after the FDA revision in all groups. The decline in EPO use trend was faster after the TREAT trial for all groups. Nephrologists were largely more responsive to evidence than primary care physicians. Differences by physician's gender, and age were not consistent across insurance populations and types of ESA. CONCLUSIONS: Physician specialty has a dominant role in prescribing decision, and that specializations with higher use of treatment (nephrologists) were more responsive to new evidence of unsafety and ineffectiveness.

Physician trajectories of abandoning long-course breast radiotherapy and their cost impact.

OBJECTIVE: To examine variation in trajectories of abandoning conventionally fractionated whole-breast irradiation (CF-WBI) for adjuvant breast radiotherapy among physician peer groups and the associated cost implications. DATA SOURCES: Medicare claims data were obtained from the Chronic Conditions Data Warehouse for fee-for-service beneficiaries with breast cancer in 2011-2014. STUDY DESIGN: We used social network methods to identify peer groups of physicians that shared patients. For each physician peer group in each time period (T1 = 2011-2012 and T2 = 2013-2014), we calculated a risk-adjusted rate of CF-WBI use among eligible women, after adjusting for patient clinical characteristics. We applied a latent class growth analysis to these risk-adjusted rates to identify distinct trajectories of CF-WBI use among physician peer groups. We further estimated potential savings to the Medicare program by accelerating abandonment of CF-WBI in T2 using a simulation model. DATA COLLECTION/EXTRACTION METHODS: Use of conventionally fractionated whole-breast irradiation was determined from Medicare claims among women ≥ 66 years of age who underwent adjuvant radiotherapy after breast conserving surgery. PRINCIPAL FINDINGS: Among 215 physician peer groups caring for 16 988 patients, there were four distinct trajectories of abandoning CF-WBI: (a) persistent high use (mean risk-adjusted utilization rate: T1 = 94.3%, T2 = 90.6%); (b) decreased high use (T1 = 81.3%, T2 = 65.3%); (c) decreased medium use (T1 = 60.1%, T2 = 44.0%); and (d) decreased low use (T1 = 31.6%, T2 = 23.6%). Peer groups with a smaller proportion of patients treated at free-standing radiation facilities and a larger proportion of physicians that were surgeons tended to follow trajectories with lower use of CF-WBI. If all physician peer groups had practice patterns in T2 similar to those in the "decreased low use" trajectory, the Medicare program could save $83.3 million (95% confidence interval: $58.5 million-$112.2 million). CONCLUSIONS: Physician peer groups had distinct trajectories of abandoning CF-WBI. Physician composition and setting of radiotherapy were associated with the different trajectories. Distinct practice patterns across the trajectories had important cost implications.

Risk of Systemic Adverse Events after Intravitreal Bevacizumab, Ranibizumab, and Aflibercept in Routine Clinical Practice.

PURPOSE: Intravitreal anti-vascular endothelial growth factor (VEGF) pharmacotherapy plays a central role in the management of neovascular age-related macular degeneration (nAMD), diabetic retinal disease (DRD), and retinal venous occlusive disease (RVO). Within clinical trials, rates of systemic serious adverse events (SAEs) after anti-VEGF treatment have been low. However, the comparative systemic safety profile of common anti-VEGF agents remains incompletely understood. The goal of this study was to compare the systemic safety of intravitreal bevacizumab, ranibizumab, and aflibercept in real-world practice. DESIGN: Retrospective cohort study. PARTICIPANTS: Using a large U.S. administrative claims database of commercially insured and Medicare Advantage enrollees, we identified adult cohorts receiving initial anti-VEGF injections for nAMD, DRD, and RVO between January 1, 2007, and June 30, 2018. We included patients with 1 year of insurance coverage before initial treatment. METHODS: We compared predefined systemic outcomes between anti-VEGF agents occurring within 180 days of treatment initiation using propensity score-weighted Cox proportional hazards models. Patients were censored upon treatment with a different anti-VEGF medication or termination of health plan coverage. MAIN OUTCOME MEASURES: Primary outcomes were acute myocardial infarction (MI), acute cerebrovascular disease (CVD), major bleeding, and all-cause hospitalization. RESULTS: A total of 87 844 patients received initial anti-VEGF injections for nAMD, DRD, and RVO between January 1, 2007, and June 30, 2018 (69 007 bevacizumab; 10 895 ranibizumab; 7942 aflibercept). Postinjection 180-day event rates per 100 patients for MI, CVD, major bleeding, and all-cause hospitalization were similar for bevacizumab (0.64, 0.59, 0.34, and 10.41, respectively), ranibizumab (0.62, 0.53, 0.40, and 9.44, respectively), and aflibercept (0.63, 0.60, 0.20, and 9.88, respectively). No differences were identified for the risk of MI, CVD, major bleeding, or all-cause hospitalization when comparing the risk-adjusted effect of treatment initiation with bevacizumab versus ranibizumab (hazard ratio [HR], 0.96 [95% confidence interval {CI}, 0.74-1.25]; HR, 1.04 [95% CI, 0.78-1.38]; HR, 0.85 [95% CI, 0.61-1.19]; HR, 1.03 [95% CI, 0.96-1.10], all P > 0.05), bevacizumab versus aflibercept (HR, 0.95 [95% CI, 0.68-1.33], HR, 0.99 [95% CI, 0.71-1.38], HR, 1.02 [95% CI, 0.60-1.74], HR, 1.01 [95% CI, 0.93-1.10], all P > 0.05), or aflibercept versus ranibizumab (HR, 0.91 [95% CI, 0.62-1.35], HR, 1.12 [95% CI, 0.74-1.69], HR, 0.96 [95% CI, 0.53-1.73], HR, 1.02 [95% CI, 0.92-1.13], all P > 0.05). CONCLUSIONS: We observed no differences in the risk of acute MI, CVD, major bleeding, or all-cause hospitalization after treatment initiation with intravitreal bevacizumab, ranibizumab, or aflibercept during routine clinical practice.

Identifying characteristics of high-poverty counties in the United States with high well-being: an observational cross-sectional study.

OBJECTIVE: To identify county characteristics associated with high versus low well-being among high-poverty counties. DESIGN: Observational cross-sectional study at the county level to investigate the associations of 29 county characteristics with the odds of a high-poverty county reporting population well-being in the top quintile versus the bottom quintile of well-being in the USA. County characteristics representing key determinants of health were drawn from the Robert Wood Johnson Foundation County Health Rankings and Roadmaps population health model. SETTING: Counties in the USA that are in the highest quartile of poverty rate. MAIN OUTCOME MEASURE: Gallup-Sharecare Well-being Index, a comprehensive population-level measure of physical, mental and social health. Counties were classified as having a well-being index score in the top or bottom 20% of all counties in the USA. RESULTS: Among 770 high-poverty counties, 72 were categorised as having high well-being and 311 as having low well-being. The high-well-being counties had a mean well-being score of 71.8 with a SD of 2.3, while the low-well-being counties had a mean well-being score of 60.2 with a SD of 2.8. Among the six domains of well-being, basic access, which includes access to housing and healthcare, and life evaluation, which includes life satisfaction and optimism, differed the most between high-being and low-well-being counties. Among 29 county characteristics tested, six were independently and significantly associated with high well-being (p<0.05). These were lower rates of preventable hospital stays, higher supply of primary care physicians, lower prevalence of smoking, lower physical inactivity, higher percentage of some college education and higher percentage of heavy drinkers. CONCLUSIONS: Among 770 high-poverty counties, approximately 9% outperformed expectations, reporting a collective well-being score in the top 20% of all counties in the USA. High-poverty counties reporting high well-being differed from high-poverty counties reporting low well-being in several characteristics.

Association of Survival With Adjuvant Chemotherapy Among Patients With Early-Stage Non-Small Cell Lung Cancer With vs Without High-Risk Clinicopathologic Features.

IMPORTANCE: Tumor size larger than 4 cm is accepted as an indication for adjuvant chemotherapy in patients with node-negative non-small cell lung cancer (NSCLC). Treatment guidelines suggest that high-risk features are also associated with the efficacy of adjuvant chemotherapy among patients with early-stage NSCLC, yet this association is understudied. OBJECTIVE: To assess the association between adjuvant chemotherapy and survival in the presence and absence of high-risk pathologic features in patients with node-negative early-stage NSCLC. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study using data from the National Cancer Database included 50 814 treatment-naive patients with a completely resected node-negative NSCLC diagnosed between January 1, 2010, and December 31, 2015. The study was limited to patients who survived at least 6 weeks after surgery (ie, estimated median time to initiate adjuvant chemotherapy after surgery) to mitigate immortal time bias. Statistical analysis was performed from December 1, 2018, to February 29, 2020. EXPOSURES: Adjuvant chemotherapy use vs observation, stratified according to the presence or absence of high-risk pathologic features (visceral pleural invasion, lymphovascular invasion, and high-grade histologic findings), sublobar surgery, and tumor size. MAIN OUTCOMES AND MEASURES: The association of high-risk pathologic features with survival after adjuvant chemotherapy vs observation was evaluated using Cox proportional hazards regression models. RESULTS: Overall, 50 814 eligible patients with NSCLC (27 365 women [53.9%]; mean [SD] age, 67.4 [9.5] years]) were identified, including 4220 (8.3%) who received adjuvant chemotherapy and 46 594 (91.7%) who did not receive adjuvant chemotherapy. Among patients with tumors 3 cm or smaller, chemotherapy was not associated with improved survival (hazard ratio [HR], 1.10; 95% CI, 0.96-1.26; P = .17). For patients with tumors larger than 3 cm to 4 cm, adjuvant chemotherapy was associated with a survival benefit among patients who underwent sublobar surgery (HR, 0.72; 95% CI, 0.56-0.93; P = .004). For tumors larger than 4 cm to 5 cm, a survival benefit was associated with adjuvant chemotherapy only in patients with at least 1 high-risk pathologic feature (HR, 0.67; 95% CI, 0.56-0.80; P = .02). For tumors larger than 5 cm, adjuvant chemotherapy was associated with a survival benefit irrespective of the presence of high-risk pathologic features (HR, 0.75; 95% CI, 0.61-0.91; P = .004). CONCLUSIONS AND RELEVANCE: In this cohort study, tumor size alone was not associated with improved efficacy of adjuvant chemotherapy in patients with early-stage (node-negative) NSCLC. High-risk clinicopathologic features and tumor size should be considered simultaneously when evaluating patients with early-stage NSCLC for adjuvant chemotherapy.

Pragmatic cluster randomized trial to evaluate effectiveness and implementation of enhanced EHR-facilitated cancer symptom control (E2C2).

BACKGROUND: The prevalence of inadequate symptom control among cancer patients is quite high despite the availability of definitive care guidelines and accurate and efficient assessment tools. METHODS: We will conduct a hybrid type 2 stepped wedge pragmatic cluster randomized clinical trial to evaluate a guideline-informed enhanced, electronic health record (EHR)-facilitated cancer symptom control (E2C2) care model. Teams of clinicians at five hospitals that care for patients with various cancers will be randomly assigned in steps to the E2C2 intervention. The E2C2 intervention will have two levels of care: level 1 will offer low-touch, automated self-management support for patients reporting moderate sleep disturbance, pain, anxiety, depression, and energy deficit symptoms or limitations in physical function (or both). Level 2 will offer nurse-managed collaborative care for patients reporting more intense (severe) symptoms or functional limitations (or both). By surveying and interviewing clinical staff, we will also evaluate whether the use of a multifaceted, evidence-based implementation strategy to support adoption and use of the E2C2 technologies improves patient and clinical outcomes. Finally, we will conduct a mixed methods evaluation to identify disparities in the adoption and implementation of the E2C2 intervention among elderly and rural-dwelling patients with cancer. DISCUSSION: The E2C2 intervention offers a pragmatic, scalable approach to delivering guideline-based symptom and function management for cancer patients. Since discrete EHR-imbedded algorithms drive defining aspects of the intervention, the approach can be efficiently disseminated and updated by specifying and modifying these centralized EHR algorithms. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03892967. Registered on 25 March 2019.

Survival After Cancer Treatment at Top-Ranked US Cancer Hospitals vs Affiliates of Top-Ranked Cancer Hospitals.

Importance: Hospital networks formed around top-ranked cancer hospitals represent an opportunity to optimize complex cancer care in the community. Objective: To compare the short- and long-term survival after complex cancer treatment at top-ranked cancer hospitals and the affiliates of top-ranked hospitals. Design, Setting, and Participants: This cohort study was conducted using data from the unabridged version of the National Cancer Database. Included patients were individuals 18 years or older who underwent surgical treatment for esophageal, gastric, lung, pancreatic, colorectal, or bladder cancer diagnosed between January 1, 2012, and December 31, 2016. Patient outcomes after complex surgical procedures for cancer at top-ranked cancer hospitals (as ranked in top 50 by US News and World Report) were compared with outcomes at affiliates of top-ranked cancer hospitals (affiliation listed in American Hospitals Association survey and confirmed by search of internet presence). Data were analyzed from July through December 2019. Exposures: Undergoing complex cancer treatment at a top-ranked cancer hospital or an affiliated hospital. Main Outcomes and Measures: The association of affiliate status with short-term survival (ie, 90-day mortality) was compared using logistic regression, and the association of affiliate status with long-term survival was compared using time-to-event models, adjusting for patient demographic, payer, clinical, and treatment factors. Results: Among 119 834 patients who underwent surgical treatment for cancer, 79 981 patients (66.7%) were treated at top-ranked cancer hospitals (median [interquartile range] age, 66 [58-74] years; 40 910 [54.9%] men) and 39 853 patients (33.3%) were treated at affiliate hospitals (median [interquartile range] age, 69 [60-77] years; 19 004 [50.0%] men). In a pooled analysis of all cancer types, adjusted perioperative mortality within 90 days of surgical treatment was higher at affiliate hospitals compared with top-ranked hospitals (odds ratio, 1.67 [95% CI, 1.49-1.89]; P < .001). Adjusted long-term survival following cancer treatment at affiliate hospitals was only 77% that of top-ranked hospitals (time ratio, 0.77 [95% CI, 0.72-0.83]; P < .001). The survival advantage was not fully explained by differences in annual surgical volume, with both long- and short-term survival remaining superior at top-ranked hospitals even after models were adjusted for volume. Conclusions and Relevance: These findings suggest that short- and long-term survival after complex cancer treatment were superior at top-ranked hospitals compared with affiliates of top-ranked hospitals. Further study of cancer care within top-ranked cancer networks could reveal collaborative opportunities to improve survival across a broad contingent of the US population.

An instrument for assessing the quality of informed consent documents for elective procedures: development and testing.

OBJECTIVE: To develop a nationally applicable tool for assessing the quality of informed consent documents for elective procedures. DESIGN: Mixed qualitative-quantitative approach. SETTING: Convened seven meetings with stakeholders to obtain input and feedback on the tool. PARTICIPANTS: Team of physician investigators, measure development experts, and a working group of nine patients and patient advocates (caregivers, advocates for vulnerable populations and patient safety experts) from different regions of the country. INTERVENTIONS: With stakeholder input, we identified elements of high-quality informed consent documents, aggregated into three domains: content, presentation and timing. Based on this comprehensive taxonomy of key elements, we convened the working group to offer input on the development of an abstraction tool to assess the quality of informed consent documents in three phases: (1) selecting the highest-priority elements to be operationalised as items in the tool; (2) iteratively refining and testing the tool using a sample of qualifying informed consent documents from eight hospitals; and (3) developing a scoring approach for the tool. Finally, we tested the reliability of the tool in a subsample of 250 informed consent documents from 25 additional hospitals. OUTCOMES: Abstraction tool to evaluate the quality of informed consent documents. RESULTS: We identified 53 elements of informed consent quality; of these, 15 were selected as highest priority for inclusion in the abstraction tool and 8 were feasible to measure. After seven cycles of iterative development and testing of survey items, and development and refinement of a training manual, two trained raters achieved high item-level agreement, ranging from 92% to 100%. CONCLUSIONS: We identified key quality elements of an informed consent document and operationalised the highest-priority elements to define a minimum standard for informed consent documents. This tool is a starting point that can enable hospitals and other providers to evaluate and improve the quality of informed consent.