Faculty Bibliography

BACKGROUND:First-line PD-inhibition in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer represents a novel clinical setting, with uncertainty concerning second-line outcomes. Specifying second-line treatment and outcomes will provide guidance in this new sequence. We performed a retrospective chart review to document the outcomes of these patients treated at our institution. PATIENTS AND METHODS/METHODS:Our cohort consisted of 43 patients with advanced urothelial cancer receiving first-line checkpoint inhibition. Baseline factors, programmed death-ligand 1 (PD-L1) status, treatments, and outcomes during and beyond the first line were obtained. Response was scored using Response Evaluation Criteria in Solid Tumors, version 1.1 criteria. Log rank tests were used to compare outcomes in prognostic subgroups, and outcome associations with PD-L1 status were analyzed with Fisher exact tests. RESULTS:A total of 43 patients received first-line atezolizumab or pembrolizumab from June 2014 until June 2018. The median age was 76.8 years, and the population was 74% male, with 60% having visceral metastases. Reasons for cisplatin ineligibility were Eastern Cooperative Oncology Group performance status 2%, 30%; renal insufficiency, 44%, and both, 21%. First-line objective response rate (ORR) was 30%, and complete response was 14%. The median overall survival was 11.7 months. Of 29 patients progressing, 17 received second-line treatment (most commonly, gemcitabine/carboplatin [10 patients]). The second-line response rate was 33%, and the ORR was 11%. The second-line median overall survival was 6.2 months. No association was found between PD-L1 status and outcomes. CONCLUSION/CONCLUSIONS:Outcomes with first-line immunotherapy are consistent with historical outcomes. The ORR after first-line checkpoint inhibition falls short of historical comparators; however, the response rate compares favorably to those of chemotherapies used in previous second-line regimens. The older age and poorer performance status may have contributed to second-line outcomes.

Atypical response patterns following immune checkpoint blockade (ICB) in Hodgkin lymphoma (HL) led to the concept of continuation of treatment beyond progression (TBP); however, the longitudinal benefit of this approach is unclear. We therefore performed a retrospective analysis of 64 patients treated with ICB - 20 who received TBP (TBP cohort) and 44 who stopped ICB at initial progression (non-TBP cohort). The TBP cohort received ICB for a median of 4.7 months after initial progression and delayed subsequent treatment by a median of 6.6 months. Despite receiving more prior lines of therapy, the TBP cohort achieved longer progression-free survival with post-ICB treatment (median 17.5m vs 6.1m, p=0.035) and longer time-to-subsequent treatment failure (TTSTF), defined as time from initial ICB progression to failure of subsequent treatment (median 34.6m vs 9.9m, p=0.003). With the limitations of a retrospective study, these results support the clinical benefit of TBP with ICB for selected patients.

Policy makers are increasingly using performance feedback that compares physicians to their peers as part of payment policy reforms. However, it is not known whether peer comparisons can improve broad outcomes, beyond changing specific individual behaviors such as reducing inappropriate prescribing of antibiotics. We conducted a cluster-randomized controlled trial with Blue Cross Blue Shield of Hawaii to examine the impact of providing peer comparisons feedback on the quality of care to primary care providers in the setting of a shift from fee-for-service to population-based payment. Over 74,000 patients and eighty-eight primary care providers across sixty-three sites were included over a period of nine months in 2016. Patients in the peer comparisons intervention group experienced a 3.1-percentage-point increase in quality scores compared to the control group-whose members received individual feedback only. This result underscores the effectiveness of peer comparisons as a way to improve health care quality, and it supports Medicare's decisions to provide comparative feedback as part of recently implemented primary care and specialty payment reform programs.

BACKGROUND:Patients' understanding of the hemoglobin A1c (HbA1c) has been linked to better diabetes care outcomes (glycemic control, self-care). This is concerning given low documented rates of HbA1c understanding. In this non-blinded, randomized trial, we compared two formats for communicating the HbA1c, selected based on input from people with diabetes, to standard presentation to assess their impact on participants' glycemic control and diabetes-related perceptions. METHODS:To design the tested formats, we interviewed 25 patients with diabetes and reviewed a range of possible formats, including color-based scales and graphs. The interviews were recorded, transcribed, and subjected to thematic analysis. Synthesizing interviewees' feedback, we selected two formats, one using a combination of words and colors (Words) and one using a color-coded graph (Graph), for further evaluation. We then randomized adults with poorly controlled diabetes to receive mailed information on their current diabetes control in one of three ways: 1) standard lab report (control), 2) Words format, or 3) Graph format. The primary outcome was HbA1c change at 6 months. Also examined were changes in participants' diabetes-related perceptions and choice of participation incentive. RESULTS:Of the 234 enrolled participants, 76.9% were Black, and their median baseline HbA1c was 9.1% (interquartile range 8.4-10.4). There were no between-arm differences in HbA1c change (- 1.04% [SD 2.2] Control vs. -0.59% [SD 2.0] Words vs. -0.54% [SD 2.1] Graph, p > 0.05 for all comparisons). Participants in the Words arm had an increase in the accuracy of their perceptions of diabetes seriousness (p = 0.04) and in the number of participants reporting a diabetes management goal (p = 0.01). CONCLUSIONS:The two patient-informed communication formats did not differentially impact glycemic control among adults with inadequately controlled diabetes. However, a significant proportion of participants in the Words arm had an increase in the accuracy of their perception of diabetes seriousness, a potential mediating factor in positive diabetes-related behavioral changes. With increasing use of patient-facing online portals, thoughtfully designed approaches for visually communicating essential, but poorly understood, information like the HbA1c to patients have the potential to facilitate interpretation and support self-management. CLINICAL TRIAL REGISTRATION/BACKGROUND:Prospectively registered as NCT01886170.

Importance/UNASSIGNED:There is limited evidence regarding how patients make choices in advance directives (ADs) or whether these choices influence subsequent care. Objective/UNASSIGNED:To examine whether default options in ADs influence care choices and clinical outcomes. Design, Setting, and Participants/UNASSIGNED:This randomized clinical trial included 515 patients who met criteria for having serious illness and agreed to participate. Patients were enrolled at 20 outpatient clinics affiliated with the University of Pennsylvania Health System and the University of Pittsburgh Medical Center from February 2014 to April 2016 and had a median follow-up of 18 months. Data analysis was conducted from November 2018 to April 2019. Interventions/UNASSIGNED:Patients were randomly assigned to complete 1 of the 3 following ADs: (1) a comfort-promoting plan of care and nonreceipt of potentially life-sustaining therapies were selected by default (comfort AD), (2) a life-extending plan of care and receipt of potentially life-sustaining therapies were selected by default (life-extending AD), or (3) no choices were preselected (standard AD). Main Outcomes and Measures/UNASSIGNED:This trial was powered to rule out a reduction in hospital-free days in the intervention groups. Secondary outcomes included choices in ADs for an overall comfort-oriented approach to care, choices to forgo 4 forms of life support, patients' quality of life, decision conflict, place of death, admissions to hospitals and intensive care units, and costs of inpatient care. Results/UNASSIGNED:Among 515 patients randomized, 10 withdrew consent and 13 were later found to be ineligible, leaving 492 (95.5%) in the modified intention-to-treat (mITT) sample (median [interquartile range] age, 63 [56-70] years; 279 [56.7%] men; 122 [24.8%] black; 363 [73.8%] with cancer). Of these, 264 (53.7%) returned legally valid ADs and were debriefed about their assigned intervention. Among these, patients completing comfort ADs were more likely to choose comfort care (54 of 85 [63.5%]) than those returning standard ADs (45 of 91 [49.5%]) or life-extending ADs (33 of 88 [37.5%]) (P = .001). Among 492 patients in the mITT sample, 57 of 168 patients [33.9%] who completed the comfort AD, 47 of 165 patients [28.5%] who completed the standard AD, and 35 of 159 patients [22.0%] who completed the life-extending AD chose comfort care (P = .02), with patients not returning ADs coded as not selecting comfort care. In mITT analyses, median (interquartile range) hospital-free days among 168 patients assigned to comfort ADs and 159 patients assigned to life-extending default ADs were each noninferior to those among 165 patients assigned to standard ADs (standard AD: 486 [306-717] days; comfort AD: 554 [296-833] days; rate ratio, 1.05; 95% CI, 0.90-1.23; P < .001; life-extending AD: 550 [325-783] days; rate ratio, 1.03; 95% CI, 0.88-1.20; P < .001). There were no differences among groups in other secondary outcomes. Conclusions and Relevance/UNASSIGNED:In this randomized clinical trial, default options in ADs altered the choices seriously ill patients made regarding their future care without changing clinical outcomes. Trial Registration/UNASSIGNED:ClinicalTrials.gov Identifier: NCT02017548.

OBJECTIVE:To evaluate whether the implementation of a new population-based primary care payment system, Population-Based Payments for Primary Care (3PC), initiated by Hawaii Medical Service Association (HMSA; the Blue Cross Blue Shield of Hawaii), was associated with changes in spending and utilization for outpatient imaging in its first year. METHODS:In this observational study, we used claims data from January 1, 2012, to December 31, 2016. We used a propensity-weighted difference-in-differences design to compare 70,284 HMSA patients in Hawaii attributed to 107 primary care physicians (PCPs) and 4 physician organizations participating in 3PC in its first year of implementation (2016) and 195,902 patients attributed to 312 PCPs and 14 physician organizations that used a fee-for-service model during the study period. The primary outcome was total spending on outpatient imaging tests, and secondary outcomes included spending and utilization by modality. RESULTS:The study included 266,186 HMSA patients (mean age of 43.3 years; 51.7% women) and 419 PCPs (mean age of 54.9 years; 34.8% women). The 3PC system was not significantly associated with changes in total spending for outpatient imaging. Of 12 secondary outcomes, only 3 were statistically significant, including changes in nuclear medicine spending (adjusted differential change = -20.1% [95% confidence interval = -27.5% to -12.1%]; P < .001) and utilization (adjusted differential change = -18.1% [95% confidence interval = -23.8 to -11.9%]; P < .001). DISCUSSION/CONCLUSIONS:The HMSA 3PC system was not associated with significant changes in total spending for outpatient imaging, though spending and utilization on nuclear medicine tests decreased.