Real-World Treatment Patterns and Clinical Outcomes Among Patients with Metastatic or Unresectable EGFR-Mutated Non-Small Cell Lung Cancer Previously Treated with Osimertinib and Platinum-Based Chemotherapy.

INTRODUCTION: For patients with epidermal growth factor receptor-mutated (EGFRm) locally advanced/metastatic non-small cell lung cancer (mNSCLC) whose disease has progressed on or after osimertinib and platinum-based chemotherapy (PBC), no uniformly accepted standard of care exists. Moreover, limited efficacy of standard treatments indicates an unmet medical need, which is being addressed by ongoing clinical investigations, including the HERTHENA-Lung01 (NCT04619004) study of patritumab deruxtecan (HER3­DXd). However, because limited information is available on real-world clinical outcomes in such patients, early-phase trials of investigational therapies lack sufficient context for comparison. This study describes the real-world clinical characteristics, treatments, and outcomes for patients with EGFRm mNSCLC who initiated a new line of therapy following previous osimertinib and PBC, including a subset matched to the HERTHENA-Lung01 population. METHODS: This retrospective analysis used a US database derived from deidentified electronic health records. The reference cohort included patients with EGFRm mNSCLC who had initiated a new line of therapy between November 13, 2015 and June 30, 2021, following prior osimertinib and PBC. A subset of patients resembling the HERTHENA-Lung01 population was then extracted from the reference cohort; this matched subset was optimized using propensity score (PS) weighting. Endpoints were real-world overall survival (rwOS) and real-world progression-free survival (rwPFS). Confirmed real-world objective response rate (rwORR; partial/complete response confirmed ≥ 28 days later) was calculated for the response-evaluable subgroups of patients (with ≥ 2 response assessments spaced ≥ 28 days apart). RESULTS: In the reference cohort (N = 273), multiple treatment regimens were used, and none was predominant. Median rwPFS and rwOS were 3.3 and 8.6 months, respectively; confirmed rwORR (response evaluable, n = 123) was 13.0%. In the matched subset (n = 126), after PS weighting, median rwPFS and rwOS were 4.2 and 9.1 months, respectively; confirmed rwORR (response evaluable, n = 57) was 14.1%. CONCLUSION: The treatment landscape for this heavily pretreated population of patients with EGFRm mNSCLC is fragmented, with no uniformly accepted standard of care. A high unmet need exists for therapeutic options that provide meaningful improvements in clinical benefit.

Bolstering the Business Case for Adoption of Shared Decision-Making Systems in Primary Care: Randomized Controlled Trial.

BACKGROUND: Limited budgets may often constrain the ability of health care delivery systems to adopt shared decision-making (SDM) systems designed to improve clinical encounters with patients and quality of care. OBJECTIVE: This study aimed to assess the impact of an SDM system shown to improve diabetes and cardiovascular patient outcomes on factors affecting revenue generation in primary care clinics. METHODS: As part of a large multisite clinic randomized controlled trial (RCT), we explored the differences in 1 care system between clinics randomized to use an SDM intervention (n=8) versus control clinics (n=9) regarding the (1) likelihood of diagnostic coding for cardiometabolic conditions using the 10th Revision of the International Classification of Diseases (ICD-10) and (2) current procedural terminology (CPT) billing codes. RESULTS: At all 24,138 encounters with care gaps targeted by the SDM system, the proportion assigned high-complexity CPT codes for level of service 5 was significantly higher at the intervention clinics (6.1%) compared to that in the control clinics (2.9%), with P<.001 and adjusted odds ratio (OR) 1.64 (95% CI 1.02-2.61). This was consistently observed across the following specific care gaps: diabetes with glycated hemoglobin A1c (HbA1c)>8% (n=8463), 7.2% vs 3.4%, P<.001, and adjusted OR 1.93 (95% CI 1.01-3.67); blood pressure above goal (n=8515), 6.5% vs 3.7%, P<.001, and adjusted OR 1.42 (95% CI 0.72-2.79); suboptimal statin management (n=17,765), 5.8% vs 3%, P<.001, and adjusted OR 1.41 (95% CI 0.76-2.61); tobacco dependency (n=7449), 7.5% vs. 3.4%, P<.001, and adjusted OR 2.14 (95% CI 1.31-3.51); BMI >30 kg/m2 (n=19,838), 6.2% vs 2.9%, P<.001, and adjusted OR 1.45 (95% CI 0.75-2.8). Compared to control clinics, intervention clinics assigned ICD-10 diagnosis codes more often for observed cardiometabolic conditions with care gaps, although the difference did not reach statistical significance. CONCLUSIONS: In this randomized study, use of a clinically effective SDM system at encounters with care gaps significantly increased the proportion of encounters assigned high-complexity (level 5) CPT codes, and it was associated with a nonsignificant increase in assigning ICD-10 codes for observed cardiometabolic conditions. TRIAL REGISTRATION: ClinicalTrials.gov NCT02451670; https://clinicaltrials.gov/ct2/show/NCT02451670.

Predictors of Mortality in Elder Patients With Proximal Humeral Fracture.

BACKGROUND: Known possible consequences of proximal humerus fractures include impaired shoulder function, decreased independence, and increased risk for mortality. The purpose of this report is to describe the survival and independence of elderly patients with fractures of the proximal humerus, treated in our institution, relative to patient characteristics and treatment method. METHODS: Retrospective cohort study from 2006 to 2012. SETTING: Community-based hospital with level 1 designation. PATIENTS/PARTICIPANTS: Three hundred nineteen patients ≥60 years who presented to the emergency department with an isolated fracture of the proximal humerus were either admitted to the inpatient ward for the organization and provision of immediate definitive care or discharged with the expectation of coordination of their care as an outpatient. Treatment was nonoperative or operative. OUTCOME MEASURES: One- and 2-year mortality. RESULTS: Significant predictors of mortality at 1 year included Charlson Comorbidity Index (CCI; continuous, hazard ratio [HR] = 1.40; 95% confidence interval [CI]: 1.06-1.86), body mass index (BMI; <25 vs ≥25; HR = 3.43; 95% CI: 1.45-8.14), and American Society of Anesthesiologists (ASA) disease severity score (3-4 vs 1-2; HR = 4.48; 95% CI: 1.21-16.55). In addition to CCI and BMI, reliance on a cane/walker/wheelchair at the time of fracture predicted mortality at 2 years (vs unassisted ambulation; HR = 3.13; 95% CI: 1.59-5.88). Although the Neer classification of fracture severity significantly correlated with inpatient admission (P < .001), it was not significantly associated with mortality or with loss of living or ambulatory independence. Among admitted patients, 64% were discharged to a facility with a higher level of care than their prefracture living facility. Twenty percent of study patients experienced a loss in ambulatory status by at least 1 level at 1 year postfracture. CONCLUSION: In a cohort of elderly patients with fractures of the proximal humerus, patient characteristics including comorbidities, ASA classification, and lower BMI were associated with increased mortality. Specifically, those admitted at the time of fracture and treated nonoperatively had the highest mortality rate and, likely, represent the frailest cohort. Those initially treated as outpatients and later treated operatively had the lowest mortality and, likely, represent the healthiest cohort. These data are inherently biased by prefracture comorbidities but help stratify our patients' mortality risk at the time of injury.

Displacement of diaphyseal clavicle fractures related to patient position and progressive displacement in the peri-injury period.

BACKGROUND: The purposes of this study were (1) to determine how supine versus upright patient position affects the measurement of diaphyseal clavicle fracture displacement, (2) to describe the incidence of progressive displacement in the peri-injury period, and (3) to investigate variables associated with the progressive displacement. METHODS: Between 2013 and 2015, patients aged 14 years or older presenting with a diaphyseal clavicle fracture within 7 days of injury were included (N = 50). A well-defined radiographic protocol was established. Nine patients underwent surgery after the second follow-up, and the remaining 41 patients, who did not undergo surgery, received the full complement of measures at the first, second, and third follow-up time points. The second follow-up (8-21 days after injury) and third follow-up (22-60 days after injury) had the same defined radiographic protocol as the first visit. The amount of displacement and angulation was measured in both the supine and upright positions on the initial injury radiographs and subsequent follow-up radiographs. RESULTS: Vertical translation was 2.4 mm (95% confidence interval, 1.8-3.0 mm) greater and angulation was 3.9° (95% confidence interval, 3.3°-4.6°) greater in the upright position. Progressive displacement occurred in 16 patients (32%). Older age (P = .015) and ipsilateral shoulder girdle or chest wall injury (P = .007) were significantly associated with progressive displacement. CONCLUSIONS: Upright radiographs evaluate maximal displacement in diaphyseal clavicle fractures. Close follow-up of nonoperatively treated clavicle fractures is warranted. Progressive displacement was more likely in older patients and/or those who had ipsilateral shoulder girdle or chest wall injury.

CD4 recovery on antiretroviral therapy is associated with decreased progression to liver disease among hepatitis C virus-infected injecting drug users.

Background. Human immunodeficiency virus (HIV) coinfection accelerates liver disease progression in individuals with chronic hepatitis C. We evaluated the associations of CD4, HIV RNA, and antiretroviral therapy (ART)-induced CD4 recovery with liver diagnoses in a prospective cohort of injecting drug users (IDUs). Methods. We evaluated 383 coinfected IDUs in the Boston area, prospectively observed for a median of 1.8 years. Liver disease progression included the first occurrence of hepatocellular carcinoma, variceal bleeding, ascites, encephalopathy, or death due to hepatic failure. Multivariable-adjusted extended Cox models were specified to estimate hazard ratios (HRs) for comparisons of CD4, change in CD4 (from nadir), and HIV RNA with respect to liver disease progression events. Results. Twenty-four persons experienced a liver disease progression event over 1155 person-years (2.1 per 100 person-years), including 20 deaths attributed to end-stage liver disease (1.7 per 100 person-years). CD4 at baseline and over follow-up strongly predicted liver disease progression (baseline CD4 <200 vs ≥200: HR = 5.23, 95% confidence interval [CI], 2.30-11.92; time-updated CD4 <200 vs ≥200: HR = 11.79, 95% CI, 4.47-31.07). Nadir CD4 was also a strong indicator (<100 vs ≥100: HR = 3.52, 95% CI, 1.54-8.06). A lack of CD4 recovery (failure to increase 100 cells over nadir) among ART initiators was associated with increased risk (HR = 7.69; 95% CI, 2.60-22.69). Human immunodeficiency virus RNA was not significantly associated with liver disease progression. Conclusions. Impaired immune function was highly predictive of liver disease progression in this cohort of IDUs, and a lack of CD4 recovery on ART was associated with increased risk of progression to HCV-associated liver disease.

Phenotypic CYP2A6 variation and the risk of pancreatic cancer.

OBJECTIVE: Cytochrome P450 2A6 (CYP2A6) is an important metabolic enzyme capable of activating several procarcinogens, including dietary and tobacco-specific nitrosamines, which have been linked to pancreatic cancer. Positive associations between high CYP2A6 activity and lung and colorectal cancers have been reported. This is the first investigation of CYP2A6 activity and pancreatic cancer. DESIGN: In this case-control study of cancer of the exocrine pancreas, phenotypic CYP2A6 activity was measured using a ratio of urinary caffeine metabolites. Demographic, smoking, dietary and medical information were obtained by questionnaire. CYP2A6 phenotype, which is not influenced by smoking status, was measured for 90 cases and 470 controls. RESULTS: When modeled as a continuous variable, and adjusted for age, sex, race, education, current smoking status and chronic pancreatitis, the odds ratio (OR) per one unit of the natural log of the CYP2A6 ratio was 1.52 (95% confidence interval, CI: 1.09-2.12). In an adjusted categorical analysis, subjects in the uppermost quartile (based on controls) of CYP2A6 activity, when compared to the lower three quartiles, carried an 80% greater risk of pancreatic cancer (OR=1.80; 95% CI: 1.07-3.02). CONCLUSIONS: High levels of CYP2A6 activity, as measured by a caffeine phenotyping assay, were positively associated with pancreatic cancer in this casecontrol study among a Midwestern U.S. population.

Anthropometric variables, physical activity, and incidence of ovarian cancer: The Iowa Women's Health Study.

BACKGROUND: Reports on the relation between anthropometric variables (height, weight) and physical activity with ovarian cancer have been inconclusive. The objective of the current study was to extend investigation of potential associations in the Iowa Women's Health Study cohort. METHODS: The relation between self-reported anthropometric variables and incident ovarian cancer was studied in a prospective cohort of women ages 55-69 years who were followed for 15 years. Two hundred twenty-three incident cases of epithelial ovarian cancer were identified by linkage to a cancer registry. RESULTS: No association was found overall between ovarian cancer and height, but a positive association was observed for serous ovarian cancers (relative risk [RR], 1.86 for highest quartile vs. lowest quartile; 95% confidence interval [95% CI], 1.06-3.29). Although current body mass index (BMI) was not associated with ovarian cancer, a BMI > or =30 kg/m2 at age 18 years appeared to be associated positively with ovarian cancer (multivariate-adjusted RR, 1.83 for BMI > or =30 kg/m2 vs. BMI <25 kg/m2; 95% CI, 0.90-3.72), and this association was stronger after exclusion of the first 2 years of follow-up (RR, 2.15; 95% CI, 1.05-4.40). In a multivariate analysis, waist-to-hip ratio was associated with ovarian cancer (RR, 1.59 for highest quartile vs. lowest quartile; 95% CI, 1.05-2.40), but a linear dose response was not found. An index that combined the frequency and intensity of leisure-time physical activity was associated positively with ovarian cancer incidence (multivariate-adjusted RR, 1.42 for high activity vs. low activity; 95% CI, 1.03-1.97). This association was particularly strong for frequency of vigorous physical activity (multivariate-adjusted RR, 2.38 for >4 times per week vs. rarely/never; 95% CI, 1.29-4.38). CONCLUSIONS: Anthropometric variables were not major risk factors for ovarian cancer in the cohort studied; however, high BMI in early adulthood and frequent and vigorous physical activity may increase the risk of ovarian cancer among postmenopausal women.

Estrogen replacement therapy and ovarian cancer.

BACKGROUND: A recent meta-analysis concluded that there was no overall association between estrogen replacement therapy (ERT) and risk of epithelial ovarian cancer. However, several subsequent studies have suggested that long-term ERT could increase ovarian cancer risk. METHODS: We prospectively examined the association of ERT with epithelial ovarian cancer among 31,381 postmenopausal women in Iowa followed for 15 years. RESULTS: Women who were using ERT at baseline had an elevated multivariate-adjusted relative risk of ovarian cancer (1.7; 95% confidence interval [CI] = 1.1-2.8) compared with never-users. Risk was higher among women who had been using ERT at baseline for more than 5 years (2.5; CI = 1.4-4.5). A time-dependent analysis likewise yielded a relative risk of 1.7 for current ERT use. Former ERT use was not associated with ovarian cancer incidence. CONCLUSIONS: Long duration of ERT use after menopause could increase the risk of epithelial ovarian cancer.