Real-World Use of Hypofractionated Radiotherapy for Primary CNS Tumors in the Elderly, and Implications on Medicare Spending.

BACKGROUND: For elderly patients with high-grade gliomas, 3-week hypofractionated radiotherapy (HFRT) is noninferior to standard long-course radiotherapy (LCRT). We analyzed real-world utilization of HFRT with and without systemic therapy in Medicare beneficiaries treated with RT for primary central nervous system (CNS) tumors using Centers for Medicare & Medicaid Services data. METHODS: Radiation modality, year, age (65-74, 75-84, or ≥85 years), and site of care (freestanding vs hospital-affiliated) were evaluated. Utilization of HFRT (11-20 fractions) versus LCRT (21-30 or 31-40 fractions) and systemic therapy was evaluated by multivariable logistic regression. Medicare spending over the 90-day episode after RT planning initiation was analyzed using multivariable linear regression. RESULTS: From 2015 to 2019, a total of 10,702 RT courses (ie, episodes) were included (28% HFRT; 65% of patients aged 65-74 years). A considerable minority died within 90 days of RT planning initiation (n=1,251; 12%), and 765 (61%) of those received HFRT. HFRT utilization increased (24% in 2015 to 31% in 2019; odds ratio [OR], 1.2 per year; 95% CI, 1.1-1.2) and was associated with older age (≥85 vs 65-74 years; OR, 6.8; 95% CI, 5.5-8.4), death within 90 days of RT planning initiation (OR, 5.0; 95% CI, 4.4-5.8), hospital-affiliated sites (OR, 1.4; 95% CI, 1.3-1.6), conventional external-beam RT (vs intensity-modulated RT; OR, 2.7; 95% CI, 2.3-3.1), and no systemic therapy (OR, 1.2; 95% CI, 1.1-1.3; P<.001 for all). Increasing use of HFRT was concentrated in hospital-affiliated sites (P=.002 for interaction). Most patients (69%) received systemic therapy with no differences by site of care (P=.12). Systemic therapy utilization increased (67% in 2015 to 71% in 2019; OR, 1.1 per year; 95% CI, 1.0-1.1) and was less likely for older patients, patients who died within 90 days of RT planning initiation, those who received conventional external-beam RT, and those who received HFRT. HFRT significantly reduced spending compared with LCRT (adjusted ß for LCRT = +$8,649; 95% CI, $8,544-$8,755), whereas spending modestly increased with systemic therapy (adjusted ß for systemic therapy = +$270; 95% CI, $176-$365). CONCLUSIONS: Although most Medicare beneficiaries received LCRT for primary brain tumors, HFRT utilization increased in hospital-affiliated centers. Despite high-level evidence for elderly patients, discrepancy in HFRT implementation by site of care persists. Further investigation is needed to understand why patients with short survival may still receive LCRT, because this has major quality-of-life and Medicare spending implications.

Development and Content Validation of Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) in Adolescents and Adults with Moderate-to-Severe AD.

INTRODUCTION: Most patient-reported outcome (PRO) instruments that measure atopic dermatitis (AD) symptoms do not have sufficient documented evidence of content validity to satisfy regulatory agency guidance for inclusion in product-labelling claims in the USA or Europe. The objective of this study was to develop a PRO instrument in accordance with regulatory agency guidance to assess daily AD symptoms during the course of therapy and to establish its content validity and psychometric properties. METHODS: The Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) daily diary was developed based on qualitative interviews with US adolescents and adults with mild-to-severe AD. Content validity, test-retest reliability, internal consistency reliability, clinically important difference, clinically important responder, convergent validity, and known-group validity were evaluated using correlational and regression methods from phase 2b data from US adults with moderate-to-severe AD who were treated with abrocitinib. RESULTS: Patient interviews conducted with US adolescents and adults with mild-to-severe AD identified 11 relevant symptoms (itch, dryness, redness, flaking, discolouration, pain, bleeding, cracking, bumps, swelling, and weeping/oozing) for inclusion in the PSAAD instrument. All PSAAD psychometric parameters were acceptable based on phase 2b data from US adults with moderate-to-severe AD. Convergent validity and known-group validity were confirmed by significant correlations between PSAAD and six other PRO measures (r = 0.24-0.91, all p ≤ 0.01) and Dermatology Life Quality Index category (p ≤ 0.0001), respectively. CONCLUSIONS: Evidence supports the PSAAD instrument validity, reliability, responsiveness and definitions of clinically important changes/differences for adults with moderate-to-severe AD.

Treatment patterns, unmet need, and impact on patient-reported outcomes of psoriatic arthritis in the United States and Europe.

Psoriatic arthritis (PsA) is a chronic, inflammatory disease. The effects of PsA real-world treatment patterns on patient-reported outcomes in the US and 5 European countries (EU5; France, Germany, Italy, Spain, UK) were evaluated. Respondents from the 2016 National Health and Wellness Survey received advanced therapies (e.g., biologic disease-modifying antirheumatic drugs [DMARDs]), other therapies, (e.g., conventional synthetic DMARDs), or no treatment. Assessments included demographics, disease severity (patient-reported), comorbidities (Charlson Comorbidity Index), health status (Short Form-36 Health Survey), depression (Patient Health Questionnaire-9), work productivity (Work Productivity and Activity Index), and treatment adherence (Morisky Medication Adherence Scale-8). Overall, 1037 respondents from the US and 947 respondents from the EU5 were included. Of these, 21.7% US and 7.3% EU5 respondents received advanced therapies; 16.6% and 28.5%, other therapies; and 61.7% and 64.2%, no treatment, respectively. During treatment with advanced or other therapies, 40.8-54.7% US and 57.7-58.9% EU5 respondents self-reported moderate or severe PsA. Respondents receiving advanced therapies had the highest Charlson Comorbidity Index score (US, 1.25; EU5, 1.42); the lowest scores were with no treatment (0.52 and 0.49, respectively). Employment was lowest with other therapies (US, 47.7%; EU5, 41.1%). Overall work impairment was reported by 57.9% US and 62.6% EU5 respondents receiving advanced therapies. Medication adherence was generally low in the US and medium in the EU5 (Morisky Medication Adherence Scale-8: low, US 40.1-46.7%, EU5, 29.0-35.2%; medium, US 29.3-36.1%, EU5 37.8-49.3%; high, US 23.8-24.0%; EU5, 21.7-27.0%). Advanced and other therapies reduced PsA severity; however, > 40% of respondents reported moderate or severe PsA during treatment. Better management and adherence may reduce unmet need and disease burden. Further work is required to improve PsA diagnosis and time to treatment initiation.

Cost Effectiveness of Lenvatinib, Sorafenib and Placebo in Treatment of Radioiodine-Refractory Differentiated Thyroid Cancer.

BACKGROUND: Lenvatinib (Lenvima®) and sorafenib (Nexavar®) are the two most recently Food and Drug Administration-approved drugs for treating radioiodine-refractory differentiated thyroid cancer (RR-DTC). Both demonstrated superior progression-free survival over placebo in their respective Phase III clinical trials. This study compared the cost-effectiveness of the two treatments with placebo from a limited societal perspective. METHODS: A Markov model was developed to estimate the costs and health benefits for treatment of RR-DTC. The probabilities and survival rates were obtained from two Phase III trials: the SELECT trial comparing lenvatinib to placebo, and the DECISION trial comparing sorafenib to placebo. A bimonthly cycle length and half-cycle correction were used for a lifetime time horizon. Medical costs and utility data were obtained from RedBook, Healthcare Cost and Utilization Project, and the published literature. All costs were adjusted to US$2015, discounted at 3% annually. Then second-order Monte Carlo simulation with distributions was conducted to obtain the acceptability curve to address the uncertainty around model inputs. RESULTS: In the base case, lenvatinib was the most cost-effective treatment compared to sorafenib (incremental cost-effectiveness ratio [ICER] = $25,275/quality-adjusted life year [QALY]) and placebo (ICER = $40,869). Sorafenib is also cost-effective compared to placebo (ICER = $64,067/QALY). The treatment decisions were found to be sensitive to the treatment costs and the health utility associated with lenvatinib and its side effects. The acceptability curve showed lenvatinib optimal 80% of time at WTP of $100,000/QALY. CONCLUSIONS: This study suggests that lenvatinib is the optimally cost-effective treatment for RR-DTC, although both lenvatinib and sorafenib are cost-effective compared to placebo.

Repeat emergency room visits for hand and wrist injuries.

PURPOSE: To characterize patients with hand or wrist injuries presenting to our university-based emergency department (ED) after a previous evaluation by an outside ED. We hypothesized that a majority of these patients did not require emergent care, most arrived during working hours, and a disproportionate number were uninsured. METHODS: We retrospectively reviewed 3,047 orthopedic hand consults from 2002 to 2010. Patients were included if our ED was the patient's second ED evaluation within 30 days for the same complaint. Demographics, diagnosis, referral instructions from the initial institution, date and time of ED visit, treatment received, and insurance status were recorded. Clinical urgency was quantified on an ordinal scale. RESULTS: A total of 325 patients met the inclusion criteria. The most common diagnoses were distal radius and metacarpal fractures. There were 266 (82%) patients with nonurgent diagnoses. A junior-level orthopedic resident treated and discharged 97% of patients from the ED. Sixty-two percent of the patients were uninsured, 32% had Medicaid, and 6% had commercial insurance or Medicare. There was a disproportionate percentage of uninsured and Medicaid patients compared with the payer mix of our state, orthopedic department, and ED. Ninety percent of patients presented on weekdays, and 84% arrived between 6 am and 6 pm. CONCLUSIONS: Most patients who met our inclusion criteria presented to our ED during regular business hours. Most were uninsured and did not have a condition that warranted urgent or emergent evaluation and treatment. With limited resources, it is important that an appropriate follow-up plan from the initial ED be in place so that patients do not have to present to a second ED for the same problem. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

The use of epidurals in abdominal wall reconstruction: an analysis of outcomes and cost.

BACKGROUND: Ventral hernias are a common, challenging, and expensive problem for general and reconstructive surgeons. The authors assessed the impact of epidurals on morbidity following abdominal wall reconstruction for hernia. METHODS: A retrospective review of abdominal wall reconstruction patients operated on between 2007 and 2012 was performed with a specific focus on the use of epidurals. Bivariate and multivariate logistic regression analyses were used to assess independent predictors of morbidity. Subgroup analyses were also performed. RESULTS: The study included 134 consecutive reconstructions performed by a single surgeon over a 5-year period at an academic teaching center. Patient groups were similar in terms of demographics, preoperative characteristics, hernia grade, and intraoperative characteristics. Epidural use was associated with a lower incidence of major surgical complications (19.7 percent versus 36.1 percent; p = 0.04) and medical complications (26.8 percent versus 54.1 percent; p = 0.001). A significant and independent reduction in medical morbidity (OR, 0.09; p ≤ 0.001) and unplanned reoperations (OR, 0.23; p = 0.052), was found with patients receiving epidurals. Furthermore, a notable trend toward reduced major surgical complications (OR, 0.45; p = 0.141) and cost savings (-$22,184; p = 0.01) was found in patients who received epidurals. Subgroup analysis did not demonstrate statistically significant reductions in major surgical morbidity in reconstruction either with (p = 0.13) or without (p = 0.07) concurrent intra abdominal procedures when epidurals were not or were used, respectively. CONCLUSIONS: Epidural use may be associated with reduced morbidity and cost savings in abdominal wall reconstruction. This effect appears to be related to reduced medical morbidity and shortened length of stay in patients undergoing more complex, concurrent intraabdominal hernia procedures. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Disparities among Blacks, Hispanics, and Whites in time from starting dialysis to kidney transplant waitlisting.

BACKGROUND: Although a longer time on dialysis before kidney transplant waitlisting has been shown for Blacks versus non-Blacks, relatively few studies have compared this outcome between Hispanics and Whites. METHODS: A multivariable analysis of 1910 (684 Black, 452 Hispanic, and 774 White) consecutive patients waitlisted at our center for a primary kidney transplant between 2005 and mid-2010 was performed for time from starting dialysis to waitlisting (months), the percentage who were preemptively waitlisted (waitlisted before starting dialysis), and time from starting dialysis to waitlisting after excluding the preemptively waitlisted patients. RESULTS: The variables associated with significantly longer median times from starting dialysis to waitlisting and less preemptive waitlisting included Medicare insurance for patients ages <65 years (by far, the most significant variable in each analysis), Black race, higher percentage of households in the patient's zip code living in poverty, being a non-U.S. citizen (for preemptive waitlisting), Medicaid insurance, waitlisted for kidney-alone (vs. kidney-pancreas) transplant, and higher body mass index (longer median times for the latter three variables). Although the effect of Black race was mostly explained by significant associations with lower socioeconomic status (Medicare insurance for patients ages <65 years and greater poverty in the patient's zip code), an unexplained component still remained. The univariable differences showing poorer outcomes for Hispanics versus Whites were smaller and completely explained in multivariable analysis by significant associations with lower socioeconomic status and non-U.S. citizenship. CONCLUSION: Black and Hispanic patients had significantly longer times from starting dialysis to waitlisting, in large part related to their lower socioeconomic status and less preemptive waitlisting. A greater focus on earlier nephrology care may help to erase much of these disparities.

The modeled lifetime cost-effectiveness of published adherence-improving interventions for antihypertensive and lipid-lowering medications.

OBJECTIVE: We sought to compare the cost-effectiveness of different interventions that have been shown to improve adherence with antihypertensive and lipid-lowering therapy, by combining a burden of nonadherence model framework with literature-based data on adherence-improving interventions. METHODS: MEDLINE was reviewed for studies that evaluated ≥1 adherence intervention compared with a control, used an adherence measure other than self-report, and followed patients for ≥6 months. Effectiveness was assessed as Relative Improvement, ratio of adherence with an intervention versus control. Costs, standardized to 12 months and adjusted to 2007 US$, and effectiveness estimates for each intervention were entered into a previously published model designed to measure the burden of nonadherence with antihypertensive and lipid-lowering medications, in a hypertensive population. Outputs included direct medical costs and incremental costs per quality-adjusted life-year (QALY) gained. RESULTS: After screening, 23 eligible adherence-improving interventions were identified from 18 studies. Relative Improvement ranged from 1.13 to 3.60. After eliminating more costly/less effective interventions, two remained. Self-monitoring, reminders, and educational materials incurred total health-care costs of $17,520, and compared with no adherence intervention, had an incremental cost-effectiveness ratio (ICER) of $4984 per QALY gained. Pharmacist/nurse management incurred total health-care costs of $17,896, and versus self-monitoring, reminders, and education had an ICER of $6358 per QALY gained. CONCLUSIONS: Of published interventions shown to improve adherence, reminders and educational materials, and a pharmacist/nurse management program, appear to be cost-effective and should be considered before other interventions. Understanding relative cost-effectiveness of adherence interventions may guide design and implementation of efficient adherence-improving programs.

Rapid assessment of trachoma in Hainan Province, China: validation of the new World Health Organization methodology.

This study was undertaken to validate a WHO methodology for the rapid assessment of trachoma. Fourteen villages were chosen by random sampling in two counties in Hainan Province, China. For the rapid assessment, trichiasis patients were identified, 50 children ages 1-10 years were examined for active trachoma, and information was collected on community access to services and community risk factors. To validate the methodology, a prevalence survey was undertaken simultaneously in the same villages. For the prevalence survey, 2428 people from 1606 households in the 14 villages were chosen by random sampling. Very little active trachoma was found by either method, although the rates of trichiasis were more substantial. Ranking of the villages by the two methods for trichiasis was highly correlated (Spearman's correlation coefficient = 0.60, p = 0.02). For active trachoma, the Spearman's correlation coefficient for the ranking of villages by the two methods was 0.40 and not significant (p = 0.14), suggesting that a correlation this close may have been seen by chance alone. The observational data showed all the villages to be at risk of active trachoma (due to poor environmental hygiene conditions), suggesting that this aspect of the WHO methodology overestimates the risk for active trachoma. We conclude that, with the exception of the community assessment of risk, this rapid assessment methodology is a valid tool for the assessment of trichiasis and possibly of active trachoma in rural communities, although the level of active trachoma in this study was too low to effectively validate that aspect of the methodology.