Patient-Centered Outcomes Research Institute Research Articles

1082-P: Cardiovascular Effectiveness of SGLT-2 Inhibitors and GLP-1 Receptor Agonists in Routine Care of Frail People with Type 2 Diabetes

Frailty is important in diabetes management but its impact on the cardiovascular (CV) effectiveness of SGLT-2i and GLP-1 RA as used in routine care is unexplored. Using Medicare claims data, we identified three pairwise 1:1 propensity score (PS) matched cohorts of people with type 2 diabetes who initiated a SGLT-2i, a GLP-1 RA, or a DPP-4i between 04/2013-12/2018. The primary outcome was a composite of major adverse CV events (MACE) including acute myocardial infarction, ischemic stroke, hospitalization for heart failure, or all-cause mortality. We estimated hazard ratios (HR) and absolute rate differences (RD) per 1`000 person-years, with their 95% CI, in each PS-matched cohort by level of frailty, using a validated claims-based frailty index (3 strata: non-frail, <0.15; pre-frail, 0.15-0.24; frail, ≥0.25) , controlling for >150 baseline covariates. We used the Wald test for homogeneity to assess treatment heterogeneity across strata. The HR for MACE associated with SGLT-2i vs. DPP4i (n=91`141 PS-matched pairs) was 0.82 (95% CI 0.72 to 0.93) in frail, 0.71 (0.67 to 0.75) in pre-frail, and 0.78 (0.71 to 0.86) in non-frail people (p for homogeneity=0.033) . The HR for MACE associated with GLP-1 RA vs. DPP4i (n=90`988 pairs) was 0.84 (0.76 to 0.93) in frail, 0.77 (95% CI 0.73 to 0.81) in pre-frail, and 0.82 (0.74 to 0.91) in non-frail people (p for h.=0.150) . The HR for MACE associated with SGLT-2i versus GLP-1 RA (n=67`067 pairs) was 0.87 (0.75 to 1.01) in frail, 0.93 (95% CI 0.87 to 1.01) in pre-frail, and 0.90 (0.79 to 1.03) in non-frail people (p for h.=0.692) . Compared to DPP-4i, the absolute benefit of either SGLT-2i or GLP-1 RA was largest in frail people [RD, -25.0 (-42.1 to -7.9) , p for h.<0.001, NNT=20; and RD, -24.9 (-39.0 to -10.7) , p for h.<0.001, NNT=21; respectively]. While, compared to DPP4i, SGLT-2i and GLP-1 RA were associated with similar relative risk reductions in MACE among people with and without frailty, their absolute benefits were largest in frail people. Disclosure A.Kutz: Research Support; Novo Nordisk. C.Gopalakrishnan: None. D.H.Kim: None. E.Patorno: Research Support; Boehringer Ingelheim International GmbH, National Institutes of Health, Patient-Centered Outcomes Research Institute. Funding National Institute on Aging (K08AG055670)

Vital best practices for antiracist patient engagement in AYA oncology research and advocacy: A Delphi study of BIPOC AYA experts.

12136 Background: In the thick of the ongoing global crises of the COVID-19 pandemic, uprisings against anti-Black racism and police brutality, and anti-Asian racism and violence, Black, indigenous, and people of color (BIPOC) adolescent and young adult (AYA) cancer patients may be particularly vulnerable and exploited. Whilst embroiled in sociopolitical complexity, BIPOC AYAs are increasingly called upon to contribute as patient advocates in AYA oncology research and advocacy. Researchers, clinicians, and advocates in AYA oncology must dismantle long-standing racism and create meaningful structural change. The purpose of this study is to derive vital best practices for implementing antiracist patient engagement in AYA oncology research and advocacy that are co-developed by BIPOC AYA cancer patients and oncology professionals. Methods: We utilized a modified Delphi technique with a panel of BIPOC AYA cancer patients (n = 32) to build consensus opinions on professional recommendations from a prior study ( Cheung et al., 2021 ), and to generate antiracist best practices in patient engagement. The Delphi study was comprised of three consecutive and iterative survey rounds over the course of 8 months in 2021; participants were BIPOC AYAs diagnosed with cancer between ages 15-36 years. Results: Results detail best practices for the implementation of antiracist patient engagement across all research activities within the Patient-Centered Outcomes Research Institute’s (PCORI) Framework for Patient Engagement. For example, BIPOC AYAs agreed with oncology professionals’ high priority recommendation for including BIPOC AYAs at the highest levels of decision making in research topic selection. As such, a best practice is for researchers to ensure that such representatives not only hold BIPOC AYA identity, but also hold direct experience with the particular oncology diagnosis, issue, or other outcome of interest. Additionally, BIPOC AYAs concurred with oncology professionals’ high priority for “transparency, honesty, and trust” as a core principle for best practices in patient engagement. They further explained that trustworthy relationships are especially important when collaborating with teens and young adults, who are developmentally just coming into their own. When describing successful experiences of inclusion, participants ranked “build collaborative relationships with BIPOC AYA communities and listen to patients not usually heard” and “recruit a diverse range of BIPOC patients and let them give actual input into the study” as the highest priority best practices. Conclusions: Findings from this study are instructional for AYA oncology researchers, clinicians, and advocates to prevent harmful tokenism and implement genuine antiracist inclusion to advance health equity. Future research should investigate best practices within unique clinical settings.

1086-P: Cardiovascular Effectiveness of SGLT2 Inhibitors: Head-to-Head Comparisons

In placebo-controlled cardiovascular (CV) outcome trials, SGLT2 inhibitors (SGLT2i) reduced the risk of CV events in patients with T2D and CV disease. However, not all trials showed consistent CV benefits across individual SGLT2i. We assembled a cohort of adults with T2D (median age 62, 57% male) , newly treated with an SGLT2i (canagliflozin, dapagliflozin, empagliflozin) from Medicare and two US commercial healthcare claims databases (4/2012 - 12/2020) . We assessed the risk of a composite event of myocardial infarction (MI) or stroke (MI/stroke) , its individual components, hospitalization for heart failure (HHF) , and mortality. To account for differences between initiators of different SGLT2i, we reweighed each group using inverse probability of treatment weights, adjusting for >130 baseline characteristics. In each database, hazard ratios (HRs) and 95% CI were estimated using Cox proportional hazards models and results were pooled using random-effects models. Compared to canagliflozin, the most frequently used SGLT2i during the study period, dapagliflozin and empagliflozin had a similar risk of MI/stroke, though empagliflozin was associated with a reduced risk of HHF [HR (95% CI) = 0.73 (0.57-0.94) ], over a median 0.65 years of follow-up. Individual SGLT2i showed a similar risk of other outcomes (Table) . This study suggests that SGLT2i have similar effectiveness on most CV outcomes and mortality in patients with T2D. Disclosure D.Abrahami: None. E.D’andrea: None. J.M.Paik: None. D.J.Wexler: Other Relationship; Elsevier, Novo Nordisk, UpToDate. B.M.Everett: Consultant; Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Lilly, Provention Bio, Inc., UpToDate, Other Relationship; American Heart Association, Research Support; Novo Nordisk. S.C.Kim: Research Support; AbbVie Inc., Bristol-Myers Squibb Company, Pfizer Inc., Roche Pharmaceuticals. E.Patorno: Research Support; Boehringer Ingelheim International GmbH, National Institutes of Health, Patient-Centered Outcomes Research Institute. Funding Patient-Centered Outcomes Research Institute (DB-2020C2-20326)

863-P: SGLT2i Use and the Risk of Nephrolithiasis in Patients with T2D

Diabetes is associated with an increased risk of kidney stones. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) might lower the risk of nephrolithiasis, as they increase urinary flow. However, a prior meta-analysis was inconclusive, and only one Danish study reported a lower risk of kidney stones. We investigated the association between SGLT2i use and the risk of nephrolithiasis in routine practice. Using claims data from 2 private health plans and Medicare (2013-2020) , we identified 331,028 pairs of 1:1 propensity score-matched adults with type 2 diabetes (T2D) initiating an SGLT2i or a DPP4 inhibitor (DPP4i) , and 358,203 pairs initiating an SGLT2i or a GLP1 receptor agonist (GLP1RA) . Our primary outcome was nephrolithiasis diagnosed by ICD codes in the inpatient or outpatient setting. We estimated hazard ratios (HRs) , rate differences (RD) and 95% confidence intervals (CI) , adjusting for 57 baseline covariates in the PS model. Over a mean follow-up of ∼months on treatment, the risk of nephrolithiasis was lower in the SGLT2i group compared with the DPP4i group (HR 0.74 [95%CI 0.71-0.77]; RD 4.0 [95%CI, -4.6, -3.4]) or the GLP1RA group (HR 0.69 [95%CI 0.67-0.72]; RD -4.1 [95%CI, -4.7, -3.5]) (Table) . Secondary definitions of the outcome based on a hospital discharge diagnosis produced consistent results. In routine care, SGLT2i use was associated with a reduced risk of nephrolithiasis, compared to DPP4i or GLP1RA use in patients with T2D. Disclosure J.M.Paik: None. H.Tesfaye: None. G.Curhan: Employee; OM1, Inc, Other Relationship; UpToDate. J.M.Mastrorilli: None. D.J.Wexler: Other Relationship; Elsevier, Novo Nordisk, UpToDate. S.C.Kim: Research Support; AbbVie Inc., Bristol-Myers Squibb Company, Pfizer Inc., Roche Pharmaceuticals. E.Patorno: Research Support; Boehringer Ingelheim International GmbH, National Institutes of Health, Patient-Centered Outcomes Research Institute.

Comparing an operation to monitoring, with or without endocrine therapy (COMET), for low-risk ductal carcinoma in situ (DCIS).

TPS616 Background: Approximately 50,000 women in the U.S. are diagnosed with ductal carcinoma in situ (DCIS) each year. Without treatment, it is estimated that only 20-30% of DCIS will lead to invasive breast cancer (IBC). However, over 97% of women are currently treated with surgery +/- radiation. An alternative to surgery is active monitoring (AM), a management approach in which mammograms/physical exams are used to monitor breast changes and determine when, or if, surgery is needed. The COMET Study will compare risks and benefits of AM versus surgery for low-risk DCIS in the setting of a Phase III multicenter prospective randomized trial. The study is funded by the Patient-Centered Outcomes Research Institute. The COMET trial opened in the U.S. in June 2017 (Clinicaltrials.gov reference: NCT02926911). In November 2021, the Data Safety Monitoring Board reviewed the trial and suggested that it continue as planned. Patient accrual will continue until 12/31/2022. Methods: The primary objective is to assess whether the 2-year ipsilateral IBC rate for AM is non-inferior to that for surgery. Secondary objectives include determining whether AM is non-inferior to surgery for 2-year mastectomy rate; breast conservation rate; contralateral breast cancer rate; overall and breast cancer-specific survival. Patient reported outcomes will enable comparison of health-related quality of life and psychosocial outcomes between surgery and AM groups at baseline, 6-months, and years 1-5. Eligibility criteria include: age > 40 at diagnosis; pathologic confirmation of grade I/II DCIS or atypia verging on DCIS without invasion by two pathologists; ER and/or PR ≥ 10%; no mass on physical exam or imaging. The accrual goal is 1200 randomized patients across 100 Alliance for Clinical Trials in Oncology sites. Sample size is estimated using a 2-group test of non-inferiority of proportions, with the 2-year IBC rate in the surgery group assumed to be 0.10 based on published studies and non-inferiority margin of 0.05. Based on a 1-sided un-pooled z-test, with alpha = 0.05, a sample size of n = 446 per group will have 80% power to detect the specified non-inferiority margin. Final analysis plan will include a per protocol component as well as a pragmatic component for patients who are randomized and decline participation in their assigned arm. Primary analyses will adjust for dropout, non-compliance and contamination by utilizing instrumental variable methods. Clinical trial information: NCT02926911.

1145-P: Individual SGLT2 Inhibitors and the Risk of Diabetic Ketoacidosis

SGLT2 inhibitors (SGLT2i) are increasingly prescribed to treat type 2 diabetes (T2D) given their cardiovascular benefits. However, SGLT2i are known to increase the risk of diabetic ketoacidosis (DKA) , a rare yet serious outcome. It remains unclear whether individual SGLT2i are associated with a differential risk of DKA. Using 3 US healthcare claims databases (1/2014 - 12/2020) we assembled 2 cohorts of adults with T2D initiating (1) individual SGLT2i, i.e., canagliflozin, dapagliflozin, or empagliflozin, for a within-class comparison between SGLT2i (cohort #1, median age=62 years, 55% male) , and (2) individual SGLT2i or dulaglutide, for comparisons between SGLT2i and an out-of-class comparison (cohort #2, median age=63 years, 54% male) . Cohorts were reweighed using inverse probability of treatment weights, accounting for >130 baseline patient characteristics. Hazard ratios (HRs) and 95% CIs were estimated for hospitalization for DKA in each database and pooled using random-effects models. Over a median follow-up of 6 months, neither empagliflozin [HR (95% CI) = 0.96 (0.78-1.19) ], or dapagliflozin [HR (95% CI) = 0.76 (0.58-1.01) ] had a differential DKA risk vs. canagliflozin. All 3 SGLT2i were associated with a similar increase in DKA risk vs. dulaglutide (Table) . In this large cohort study, we found no difference in the risk of DKA across individual SGLT2i, but all SGLT2i types were associated with an increased risk of DKA vs. dulaglutide. Disclosure D.Abrahami: None. E.D'andrea: None. S.C.Kim: Research Support; AbbVie Inc., Bristol-Myers Squibb Company, Pfizer Inc., Roche Pharmaceuticals. D.J.Wexler: Other Relationship; Elsevier, Novo Nordisk, UpToDate. J.M.Paik: None. E.Patorno: Research Support; Boehringer Ingelheim International GmbH, National Institutes of Health, Patient-Centered Outcomes Research Institute. Funding Patient-Centered Outcomes Research Institute (DB-2020C2-20326)

1146-P: SGLT2 Inhibitors and the Risk of Early Bladder Cancer Events

SGLT2 inhibitors (SGLT2is) have been shown to reduce the risk of cardiovascular and mortality events in large cardiovascular outcome trials in patients with type 2 diabetes. However, their safety profile is controversial, with some trials reporting imbalances in bladder cancer events, all of which occurred relatively soon after randomization. To address this safety concern, we used 3 US healthcare claims databases and 1 UK primary care database (01/2013-12/2020) . In each database, we identified adults newly treated with either SGLT2is (total n=453,726) or GLP-1 receptor agonists (GLP1RAs, n=375,990) (comparison #1) , and SGLT2is (n=347,055) or DPP-4 inhibitors (DPP4is, n=854,141) (comparison #2) . Propensity score-based fine stratification was used to reweigh the cohorts, adjusting for a wide range of patient characteristics at baseline. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for bladder cancer in each database using Cox proportional hazards models. After a median follow-up of 1.8 years, use of SGLT2is may slightly reduce the risk of bladder cancer, compared to GLP1RAs [HR (95% CI) =0.90 (0.81-1.00) ]. Compared to use of DPP4is, SGLT2is are not associated with bladder cancer incidence [HR (95% CI) : 1.00 (0.91-1.11) ] after a median follow-up of 2.0 years (Table) . Overall, the results of this large international cohort study provide reassurance on the short-term effects of SGLT2is on bladder cancer incidence. Disclosure D.Abrahami: None. H.Tesfaye: None. H.Yin: None. O.Yu: None. R.W.Platt: Consultant; Amgen Inc., Biogen, Merck & Co., Inc., Nant Pharma, Pfizer Inc. S.Schneeweiss: None. E.Patorno: Research Support; Boehringer Ingelheim International GmbH, National Institutes of Health, Patient-Centered Outcomes Research Institute. L.Azoulay: Consultant; Pfizer Inc. Funding Canadian Institutes of Health Research (PJT-169040)

179-OR: Cardiovascular Effectiveness of Empagliflozin vs. Glucagon-Like Peptide-1 Receptor Agonists or Liraglutide in the EMPRISE Study

Within the EMPRISE® monitoring program, we evaluated the cardiovascular effectiveness of empagliflozin (EMPA) vs. glucagon-like peptide-1 receptor agonists (GLP1RA) or liraglutide using data from Medicare and 2 U.S. commercial claims databases [2014- (2018 for Medicare) ]. We identified patients ≥18 years with type 2 diabetes initiating (i) EMPA vs. GLP1-RA or (ii) EMPA vs. liraglutide. Primary outcomes were hospitalization for heart failure (HHF) , myocardial infarction (MI) , stroke, and all-cause mortality (Medicare only) . After 1:1 propensity score matching, we estimated pooled HR (95% CI) overall and in subgroups of patients with and without baseline cardiovascular disease (CVD) . We identified 105,955 pairs of EMPA vs. GLP1RA initiators and 72,498 pairs of EMPA vs. liraglutide initiators (Table) . Relative to GLP1RA, EMPA had a lower risk of HHF [HR:0.62 (95% CI, 0.53, 0.71) ] and a similar risk of MI [0.95 (0.85, 1.07) ], stroke [1. (0.94, 1.27) ], and mortality [0.91 (0.77, 1.08) ]. Results were consistent for patients with and without CVD. When we compared EMPA vs. liraglutide, estimates were similar to those from GLP1 RA, both overall and across subgroups. Among real-world patients, EMPA was associated with a reduced risk of HHF, but with similar risk of MI, stroke, and mortality, across the broad spectrum of CVD, compared with GLP-1RA overall or liraglutide. Disclosure P.T.Htoo: Employee; Johnson & Johnson. S.Schneeweiss: None. E.Patorno: Research Support; Boehringer Ingelheim International GmbH, National Institutes of Health, Patient-Centered Outcomes Research Institute. H.Tesfaye: None. J.M.Paik: None. D.J.Wexler: Other Relationship; Elsevier, Novo Nordisk, UpToDate. M.Najafzadeh: None. R.Glynn: Research Support; Amarin Corporation, AstraZeneca, Kowa Pharmaceuticals America, Inc., Novartis AG, Pfizer Inc. A.Deruaz-luyet: Employee; Boehringer Ingelheim International GmbH, Other Relationship; IQVIA Inc., Sanofi. S.F.Fazeli farsani: Employee; Boehringer Ingelheim International GmbH. L.Koeneman: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.

0774 Positive Airway Pressure Utilization, Major Adverse Cardiovascular Events Incidence Risk and Mortality in Medicare Beneficiaries with Obstructive Sleep Apnea

Abstract Introduction Positive airway pressure (PAP) is the first line treatment for moderate-severe or symptomatic obstructive sleep apnea (OSA). Randomized controlled trials have established that PAP therapy has beneficial impact on cardiovascular and metabolic functions. However, evidence on the benefits of PAP for preventing major adverse cardiovascular events (MACE) is limited. We aimed to determine the association between PAP utilization and incidence of MACE and all-cause mortality in a large sample of Medicare beneficiaries. Methods Medicare beneficiaries (>65 years) with at least 5 years of consecutive enrollment to part A and B and ≥2 distinct OSA claims were collected from multi-state (Kansas, Missouri, Iowa, Wisconsin, Nebraska, Minnesota, Texas, Utah, North Dakota, South Dakota and Indiana), multi-year (2011-2017) Medicare fee-for-service claims data. We further required at least 1-year enrollment before the first OSA claim. Evidence of PAP utilization and index date was defined based on the first Healthcare Common Procedure Coding System PAP initiation codes (E0601, E0470, E0471) after first OSA diagnosis. MACE was defined as the first occurrence of myocardial infarction, coronary revascularization, stroke, or heart failure (identified by diagnostic and procedure code claims) after PAP initiation. Analyses were adjusted by age at initial OSA diagnosis, sex, race and presence of hypertension, type 2 diabetes, obesity, and evidence of MACE prior to the index date. Results Our sample included 212,445 eligible Medicare beneficiaries with evidence of OSA diagnosis (mean [SD] age 75 [5.7] years; 45.2% women; median [Q1, Q3] follow-up 4 [2.0, 4.9] years at censoring). Five-year MACE cumulative incidence rate was 59.3% and the mortality rate was 17.8%. In adjusted analyses, OSA patients with evidence of PAP utilization (50.8%) had significantly lower MACE incidence risk (HR=0.812; 95%CI=0.803-0.822; p<0.0001) when compared to those without evidence of using PAP. OSA patients with evidence of PAP utilization also had significantly lower mortality risk (HR=0.575; 95%CI=0.560-0.591; p<0.0001). Pre-existing hypertension, type II diabetes and obesity were also significantly associated with increased mortality and MACE risk. Conclusion PAP utilization based on device initiation derived from claims data is associated with lower MACE incidence and mortality in older adults that are Medicare beneficiaries. Support (If Any) American Heart Association (20CDA35310360), Patient-Centered Outcomes Research Institute (RI-CRN-2020-003-IC); NIH CTSA NCATS Frontiers: University of Kansas Clinical and Translational Science Institute (UL1TR002366); Tier 2 grant, University of Missouri.

0441 Treating Insomnia Disorder in Black Women: Results from an Internet-Based, Randomized Clinical Trial of a Culturally Tailored Intervention

Abstract Introduction Black women are at high risk for insomnia. Despite considerable interest in addressing sleep health disparities, there is very limited research investigating the efficacy of gold standard treatment (cognitive-behavioral therapy for insomnia; CBT-I) among this minority population. Further, we are not aware of any data studying whether a culturally tailored intervention would improve treatment efficacy and/or engagement among Black women. Methods We conducted a randomized clinical trial within a national, longitudinal cohort study (Black Women’s Health Study; BWHS). BWHS participants with elevated insomnia symptoms were randomized to receive: (1) automated Internet-delivered CBT-I (Sleep Healthy Using the Internet; SHUTi); (2) a stakeholder-informed, tailored version of SHUTi for Black women (SHUTi-BWHS); or (3) patient education about sleep (PE). Primary outcomes were insomnia severity (Insomnia Severity Index; ISI) and treatment engagement (completion of the intervention). We hypothesized that both SHUTi and SHUTi-BWHS would lead to significantly decreased insomnia severity compared to PE, and that SHUTi-BWHS participants would be more likely to complete the intervention. Results Three-hundred and thirty-three Black women (mean age=59.3 years) were enrolled in the trial. Those randomized to receive either SHUTi or SHUTi-BWHS had greater reductions in ISI scores at 6-month follow-up (-10.0 and -9.3 points, respectively) compared to PE (-3.6 points). More participants randomized to SHUTi-BWHS completed the intervention compared to those randomized to SHUTi (78.2% vs 64.8%; p<.01). Participants who completed either SHUTi or SHUTi-BWHS showed greater reductions in insomnia severity compared to non-completers (-10.4 vs -6.2 points; p<.01). Conclusion Both SHUTi and SHUTi-BWHS improved sleep outcomes more than an active control. The culturally tailored SHUTi-BWHS program was more effective at engaging participants with the program as a greater proportion completed the full intervention, which was associated with greater improvements in sleep outcomes. These compelling data demonstrate that offering a culturally adapted program is a possible path in efforts to address the sleep health disparities facing Black Americans. Support (If Any) This trial was funded by Patient-Centered Outcomes Research Institute grant AD-2017C1-6314. National Cancer Institute grant U01 CA164974 supports the BWHS infrastructure.

Harm-to-Benefit of Three Decades of Prostate Cancer Screening in Black Men

BackgroundProstate-specific antigen screening has profoundly affected the epidemiology of prostate cancer in the United States. Persistent racial disparities in outcomes for Black men warrant re-examination of the harms of screening relative to its cancer-specific mortality benefits in this population.MethodsWe estimated overdiagnoses and overtreatment of prostate cancer for men of all races and for Black men 50 to 84 years of age until 2016, the most recent year with treatment data available, using excess incidence relative to 1986 based on the Surveillance, Epidemiology, and End Results registry and U.S. Census data as well as an established microsimulation model of prostate cancer natural history. Combining estimates with plausible mortality benefit, we calculated numbers needed to diagnose (NND) and treat (NNT) to prevent one prostate cancer death.ResultsFor men of all races, we estimated 1.5 to 1.9 million (range between estimation approaches) overdiagnosed and 0.9 to 1.5 million overtreated prostate cancers by 2016. Assuming that half of the 270,000 prostate cancer deaths avoided by 2016 were attributable to screening, the NND and the NNT would be 11 to 14 and 7 to 11 for men of all races and 8 to 12 and 5 to 9 for Black men, respectively. Alternative estimates incorporating a lag between incidence and mortality resulted in a NND and a NNT for Black men that reached well into the low single digits.ConclusionsComplementary approaches to quantifying overdiagnosis indicate a harm-benefit tradeoff of prostate-specific antigen screening that is more favorable for Black men than for men of all races considered together. Our findings highlight the need to account for the increased value of screening in Black men in clinical guidelines. (Funded by the Patient-Centered Outcomes Research Institute, the National Cancer Institute, the Bristol Myers Squibb Foundation, and the Damon Runyon Cancer Research Foundation.)

Changing the Trajectory of Heart Failure and Kidney Disease: A Call for Action.

Changing the Trajectory of Heart Failure and Kidney Disease: A Call for Action.

MP28-08 BURDEN OF DEPRESSION AND ANXIETY IN MEN WITH HIGH-RISK, INTERMEDIATE-RISK OR LOW-RISK PROSTATE CANCER

You have accessJournal of UrologyCME1 May 2022MP28-08 BURDEN OF DEPRESSION AND ANXIETY IN MEN WITH HIGH-RISK, INTERMEDIATE-RISK OR LOW-RISK PROSTATE CANCER Sumedha Chhatre, S. Bruce Malkowicz, and Ravishankar Jayadevappa Sumedha ChhatreSumedha Chhatre More articles by this author , S. Bruce MalkowiczS. Bruce Malkowicz More articles by this author , and Ravishankar JayadevappaRavishankar Jayadevappa More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002571.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: While psychological difficulties such as depression and anxiety facing men with prostate cancer are acknowledged widely, they remain understudied. Objective was to assess the short-term and log-term burden of depression and anxiety by treatment type across different risk categories of prostate cancer. METHODS: We used data from a multi-centered randomized controlled study among localized prostate cancer patients. Outcomes were assessed at baseline, and at 3, 6, 12 and 24-month follow-up. Treatments were robotic-assisted laparoscopic radical prostatectomy, radiation therapy and active surveillance. Participants were categorized into risk groups as: low risk (PSA <10 ng/ml, Gleason ≤ 6, clinical stage T1-2a), intermediate risk (PSA 10 -20 ng/ml, Gleason 7, clinical stage T2b), and high risk (PSA > 20, Gleason ≥8, clinical stage T2c-3a). Depression was assessed using Center for Epidemiologic Studies Depression (CES-D) scale. CES-D score > 16 indicates depression. Anxiety was assessed using Scale for Prostate Cancer (MAX-PC). MAX-PC score > 27 indicates anxiety. Proportion of participants with depression and anxiety were compared by treatment type, for each prostate cancer risk category. RESULTS: Total of 743 localized prostate cancer patients were recruited for the study. Retention rate was > 75% during follow-up. 34% patients were low-risk, 32% were intermediate-risk and 34% were high-risk. For all risk groups, proportion of patients with depression increased between baseline and 24-month, for all treatment types. For low-risk group, at 24-month, proportion of patients on active surveillance who were depressed was lower than surgery and radiation groups (25% vs. 46% and 43%). For intermediate-risk and high risk-group, at 24-month, proportion of patients with depression was comparable between surgery and radiation. Similar pattern was observed for burden of anxiety. CONCLUSIONS: Ours is one of the largest randomized controlled study that has assessed the burden of depression and anxiety in localized prostate cancer patients. In our study, we observed that a substantial proportion of localized prostate cancer patients experienced depression and anxiety. Especially, in the follow-up period, the proportion of patients with depression and anxiety increased significantly. Future studies need to examine the effects of depression and anxiety on process of care and outcomes; and the pathways. Patient-centered survivorship care strategies are needed for reducing depression and anxiety and improving outcomes in prostate cancer care. Source of Funding: Patient-centered Outcomes Research Institute (PCORI) CE-12-11-4973 © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e463 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sumedha Chhatre More articles by this author S. Bruce Malkowicz More articles by this author Ravishankar Jayadevappa More articles by this author Expand All Advertisement PDF DownloadLoading ...

PD25-03 ASSOCIATION BETWEEN FINANCIAL BURDEN AND TREATMENT REGRET IN MEN WITH LOCALIZED PROSTATE CANCER

You have accessJournal of UrologyCME1 May 2022PD25-03 ASSOCIATION BETWEEN FINANCIAL BURDEN AND TREATMENT REGRET IN MEN WITH LOCALIZED PROSTATE CANCER Daniel D. Joyce, Christopher J. D. Wallis, Li-Ching Huang, Karen E. Hoffman, Zhiguo Zhao, Tatsuki Koyama, Ralph Conwill, David F. Penson, and Daniel A. Barocas Daniel D. JoyceDaniel D. Joyce More articles by this author , Christopher J. D. WallisChristopher J. D. Wallis More articles by this author , Li-Ching HuangLi-Ching Huang More articles by this author , Karen E. HoffmanKaren E. Hoffman More articles by this author , Zhiguo ZhaoZhiguo Zhao More articles by this author , Tatsuki KoyamaTatsuki Koyama More articles by this author , Ralph ConwillRalph Conwill More articles by this author , David F. PensonDavid F. Penson More articles by this author , and Daniel A. BarocasDaniel A. Barocas More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002567.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We sought to understand the association between financial burden and treatment regret in men with localized prostate cancer to better understand the importance of inclusion of financial discussions in patient counseling. METHODS: Utilizing the multicenter, population-based Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) dataset, we identified all men accrued between 2011 and 2012 who underwent surgery, radiation, or active surveillance as primary management for localized prostate cancer. Patient-reported functional outcomes were assessed at baseline and longitudinally through 5 years using the 26-item Expanded Prostate Index Composite questionnaire. Treatment regret was assessed at 3- and 5-year follow-up using Clark’s validated scale. Financial burden was similarly evaluated at 3 and 5 years using a previously published 4-item questionnaire. The association between financial burden and treatment regret was assessed using multivariable logistic regression controlling for demographics, disease characteristics, treatment, functional outcomes, and patient expectations. RESULTS: Of the 2,924 men who met inclusion criteria, both regret and financial burden assessments were available for 80.6% (n=2,359). Prostate cancer management included surgery (n=1,256, 53.2%), radiation (n=787, 33.4%), and active surveillance (n=316, 13.4%). Financial burden from “finances in general” was associated with treatment regret at 3 and 5 years, after adjusting for potential confounders (OR 2.47, 95% CI 1.33, 4.57). Similar associations with financial burden from direct costs, such as treatment (OR 1.02, 95% CI 0.47, 2.21), clinic visit (OR 1.85, 95% CI 0.92, 3.71), and health insurance costs (OR 1.71, 95% CI 0.89, 3.30) were not observed (see Table). CONCLUSIONS: In this representative, population-based sample of men with localized prostate cancer, we observed associations between overall financial burden and treatment regret. The lack of association between treatment regret and measures of financial burden due to direct treatment costs may indicate a more profound impact on patients from indirect costs and should guide future efforts to address financial toxicity in prostate cancer management. Source of Funding: This study was supported by the Agency for Healthcare Research and Quality (1R01HS019356, 1R01HS022640) and the Patient-Centered Outcomes Research Institute (CE-12-11-4667). Data management was facilitated by Vanderbilt University’s Research Electronic Data Capture (REDCap) system, which is supported by the Vanderbilt Institute for Clinical and Translational Research grant (UL1TR000011 from NCATS/NIH) © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e422 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Daniel D. Joyce More articles by this author Christopher J. D. Wallis More articles by this author Li-Ching Huang More articles by this author Karen E. Hoffman More articles by this author Zhiguo Zhao More articles by this author Tatsuki Koyama More articles by this author Ralph Conwill More articles by this author David F. Penson More articles by this author Daniel A. Barocas More articles by this author Expand All Advertisement PDF DownloadLoading ...

PD26-10 COMPARISON OF INTRAVESICAL THERAPY AND SURGERY AS TREATMENT OPTIONS FOR RECURRENT BLADDER CANCER (CISTO): UPDATE ON AN ONGOING MULTICENTER PRAGMATIC STUDY

You have accessJournal of UrologyCME1 May 2022PD26-10 COMPARISON OF INTRAVESICAL THERAPY AND SURGERY AS TREATMENT OPTIONS FOR RECURRENT BLADDER CANCER (CISTO): UPDATE ON AN ONGOING MULTICENTER PRAGMATIC STUDY John Gore, Erika Wolff, Bryan Comstock, Kristin Follmer, Michael Nash, On Ho, Stephanie Chisolm, Doug MacLean, Jenney Lee, Sarah Lawrence, Danielle Lavallee, Yair Lotan, Gary Steinberg, Sima Porten, Larry Kessler, Angela Smith, and CISTO Collaborative John GoreJohn Gore More articles by this author , Erika WolffErika Wolff More articles by this author , Bryan ComstockBryan Comstock More articles by this author , Kristin FollmerKristin Follmer More articles by this author , Michael NashMichael Nash More articles by this author , On HoOn Ho More articles by this author , Stephanie ChisolmStephanie Chisolm More articles by this author , Doug MacLeanDoug MacLean More articles by this author , Jenney LeeJenney Lee More articles by this author , Sarah LawrenceSarah Lawrence More articles by this author , Danielle LavalleeDanielle Lavallee More articles by this author , Yair LotanYair Lotan More articles by this author , Gary SteinbergGary Steinberg More articles by this author , Sima PortenSima Porten More articles by this author , Larry KesslerLarry Kessler More articles by this author , Angela SmithAngela Smith More articles by this author , and CISTO Collaborative More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002574.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patients with non-muscle-invasive bladder cancer (NMIBC) that recurs after treatment with intravesical Bacillus Calmette-Guerin (BCG) must weigh the risk of progression of bladder cancer and loss of a window of potential cure with medical therapy against the risk of morbidity and loss of quality of life (QOL) with radical cystectomy. The CISTO Study (NCT03933826) is a pragmatic, prospective observational cohort study comparing medical therapy (i.e., intravesical therapy or systemic immunotherapy) with radical cystectomy for recurrent high-risk NMIBC. Here we report on the design and progress of the CISTO Study. METHODS: 900 patients with recurrent high-risk NMIBC that has failed first-line BCG and who have chosen to undergo standard of care treatment will be enrolled. Patient stakeholders helped determine the primary outcome: 12-month patient-reported QOL using the EORTC QLQ-C30. Secondary outcomes include urinary and sexual function, decisional regret, financial distress, healthcare utilization, return to work/normal activities, progression, and recurrence-free, metastasis-free, and overall survival. Participants will be followed for up to 3 years. RESULTS: Enrollment is active at 32 sites across the US, including 23 university-based centers and 9 community sites. As of November 1, 2021, 173 participants have been enrolled, 104 of whom chose medical therapy and 69 of whom chose radical cystectomy. The completion rate for the primary outcome of QOL at 12 months is 94% (15 out of 16 participants to date). The inclusion of electronic consent and collection of PROs allowed recruitment and follow-up to continue remotely during the COVID-19 pandemic. Significant pandemic-related challenges have included slow study start-up at sites, staffing, periods of suspension, and delays in patients obtaining care. Strategies to address these challenges include improved methods for onboarding and training sites, all-site communication, confirming study eligibility, abstracting EHR data, and remote monitoring while adhering to the highest study standards. CONCLUSIONS: The CISTO Study will compare patient reported outcomes for those undergoing medical therapy with radical cystectomy for recurrent high-risk NMIBC. The CISTO Study has the potential to fill critical evidence gaps and provide for personalized, patient-centered care. Source of Funding: This work was supported through a Patient-Centered Outcomes Research Institute (PCORI) Award (PCS-2017C3-9380) © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e491 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information John Gore More articles by this author Erika Wolff More articles by this author Bryan Comstock More articles by this author Kristin Follmer More articles by this author Michael Nash More articles by this author On Ho More articles by this author Stephanie Chisolm More articles by this author Doug MacLean More articles by this author Jenney Lee More articles by this author Sarah Lawrence More articles by this author Danielle Lavallee More articles by this author Yair Lotan More articles by this author Gary Steinberg More articles by this author Sima Porten More articles by this author Larry Kessler More articles by this author Angela Smith More articles by this author CISTO Collaborative More articles by this author Expand All Advertisement PDF DownloadLoading ...

Reliever-Triggered Inhaled Glucocorticoid in Black and Latinx Adults with Asthma

BackgroundBlack and Latinx patients bear a disproportionate burden of asthma. Efforts to reduce the disproportionate morbidity have been mostly unsuccessful, and guideline recommendations have not been based on studies in these populations.MethodsIn this pragmatic, open-label trial, we randomly assigned Black and Latinx adults with moderate-to-severe asthma to use a patient-activated, reliever-triggered inhaled glucocorticoid strategy (beclomethasone dipropionate, 80 μg) plus usual care (intervention) or to continue usual care. Participants had one instructional visit followed by 15 monthly questionnaires. The primary end point was the annualized rate of severe asthma exacerbations. Secondary end points included monthly asthma control as measured with the Asthma Control Test (ACT; range, 5 [poor] to 25 [complete control]), quality of life as measured with the Asthma Symptom Utility Index (ASUI; range, 0 to 1, with lower scores indicating greater impairment), and participant-reported missed days of work, school, or usual activities. Safety was also assessed.ResultsOf 1201 adults (603 Black and 598 Latinx), 600 were assigned to the intervention group and 601 to the usual-care group. The annualized rate of severe asthma exacerbations was 0.69 (95% confidence interval [CI], 0.61 to 0.78) in the intervention group and 0.82 (95% CI, 0.73 to 0.92) in the usual-care group (hazard ratio, 0.85; 95% CI, 0.72 to 0.999; P=0.048). ACT scores increased by 3.4 points (95% CI, 3.1 to 3.6) in the intervention group and by 2.5 points (95% CI, 2.3 to 2.8) in the usual-care group (difference, 0.9; 95% CI, 0.5 to 1.2); ASUI scores increased by 0.12 points (95% CI, 0.11 to 0.13) and 0.08 points (95% CI, 0.07 to 0.09), respectively (difference, 0.04; 95% CI, 0.02 to 0.05). The annualized rate of missed days was 13.4 in the intervention group and 16.8 in the usual-care group (rate ratio, 0.80; 95% CI, 0.67 to 0.95). Serious adverse events occurred in 12.2% of the participants, with an even distribution between the groups.ConclusionsAmong Black and Latinx adults with moderate-to-severe asthma, provision of an inhaled glucocorticoid and one-time instruction on its use, added to usual care, led to a lower rate of severe asthma exacerbations. (Funded by the Patient-Centered Outcomes Research Institute and others; PREPARE ClinicalTrials.gov number, NCT02995733.)

Understanding the Influence and Impact of Stakeholder Engagement in Patient-centered Outcomes Research: a Qualitative Study

BackgroundEngaging patients and other stakeholders as partners in research offers promise in improving the relevance and usefulness of research findings.ObjectiveTo explore the influence and impact of patient and other stakeholder engagement on the planning and conduct of comparative effectiveness research studies.DesignQualitative study with virtual, hour-long semi-structured interviews.ParticipantsFifty-eight researchers and fifty-one partners from a diverse purposeful sample of fifty-eight studies funded by the Patient-Centered Outcomes Research Institute (PCORI).ApproachContent and thematic analysis of interview data.Key ResultsDescribed as an integral, long-term part of the research process, engagement influenced all aspects of the design and execution of studies. Partner influence was also dynamic and iterative, taking different forms over the course of the study. Across studies, we identified 387 discrete examples of influence and classified each as one of five types of influence, derived inductively from the interview data: co-producing, redirecting, refining, confirming, and limited. Most projects exhibited multiple types of influence, with 50 researchers and 41 partners reporting two or more types of influence within a project. Of the 387 examples of stakeholder influence, 306 had at least one reported impact on the study. Such impacts included changes to reflect the needs and preferences of patients or clinicians, as well as impacts on study feasibility, study quality, engagement scope or quality, and study relevance. Both researchers and partners identified multiple types of impact within projects, with 42 researchers and 38 partners reporting two or more types within a project. Because of these observable impacts, researchers and partners described engagement as worthwhile.ConclusionsFindings provide insights for funders and institutions supporting engagement, measurement efforts, and clinical researchers aiming to conduct engaged research and observe similar influences and impacts in their own studies.

Optimizing Outcomes of Treatment-Resistant Depression (TRD) in Older Adults (OPTIMUM): Measures of Psychological Well-Being

<h3>Introduction</h3> The "Optimizing Antidepressants for Treatment-Resistant Depression in Older Adults" (OPTIMUM) study, funded by the Patient-Centered Outcomes Research Institute, is a 5-center collaboration that randomized 621 depressed individuals aged 60+ with treatment-resistant depression (TRD), the largest pharmacotherapy trial of TRD in late life. A key goal of this pragmatic trial was to measure outcomes of interest to patients, which in this trial included psychological wellbeing. This construct is closely tied to psychological and physical functioning and can be measured by self-report. <h3>Methods</h3> Participants were recruited and randomized if they were 60 years and older, met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for Major Depressive Disorder, and had a score of 10 or higher on the Patient Health Questionnaire (PHQ-9), despite having been treated with at least two antidepressants with an adequate dosage and for at least four weeks (with previous psychotropic medications being different from the medications being testing in OPTIMUM). Upon study entry, participants were randomized to one of three strategies: augmentation with aripiprazole, augmentation with bupropion, or switch to bupropion. Treatment effectiveness was assessed using the Montgomery Asberg Rating Scale (MADRS) after ten weeks of treatment. Participants were also tested at the beginning and end of this 10-week step with the NIH Toolbox Psychological Well-being battery. Two wellbeing scales were used: positive affect (34 items) and general life satisfaction (16 items). Positive affect is characterized as happiness, contentment, and interest in pleasurable or achievement–relevant activities. Each item is scored on a 5-point scale ranging from "not at all" to "very much". General life satisfaction is the cognitive evaluation of life experiences; items assessing this concept are usually phrased in a general or global way rather than having a momentary or recent recall period. These items administered are scored on either a 5-point or 7-point scale ranging from "strongly disagree" to "strongly agree." <h3>Results</h3> Of the 621 study participants, 212 were randomized to augmentation with aripiprazole, 206 to augmentation with bupropion, and 203 to a switch to bupropion. Participants randomized to augmentation with either aripiprazole or bupropion showed a statistically significant improvement in their general life satisfaction subscale score (aripipirazole: 2.99, p< 0.0001; bupropion: 2.61, p=0.0001), while those switched to bupropion did not. Participants in either of the two augmentation arms also showed a statistically significant improvement in positive affect (aripiprazole: 5.35, p< 0.0001; bupropion: 5.02, p< 0.0001) while those switching to bupropion did not. <h3>Conclusions</h3> Among older adults with TRD, augmentation with aripiprazole or bupropion was associated with a statistically significant improvement in psychological well-being and positive affect, while a switch to bupropion monotherapy did not. Further research is needed to replicate findings. <h3>This research was funded by</h3> Patient-Centered Outcomes Research Institute (PCORI)

Augmenting Vs. Switching Antidepressant for Treatment Resistant Depression in Older adults: Results from the Optimum Study

This symposium will provide new information from a large, recently-completed comparative effectiveness trial called “OPTIMUM”, which studied augmentation vs. switch strategies for Treatment Resistant Depression (TRD) in older adults, yielding practical recommendations for treatment. Treatment resistance is common in older depressed adults, as ∼30% fail to remit with first-line antidepressant pharmacotherapies; namely SSRIs and SNRIs. Next-line strategies for TRD include augmentation with aripiprazole, augmentation with bupropion, and switch to bupropion. For those with higher levels of treatment resistance, older but well-known strategies are lithium augmentation and a switch to a secondary amine tricyclic (namely nortriptyline). Understanding the benefits vs. risk of these medication strategies is crucial for this population, which has high morbidity from depression but also significant risks from pharmacotherapy. The "Optimizing antidepressants for TRD in older adults" (OPTIMUM) study, funded by the Patient-Centered Outcomes Research Institute, is a 5-center collaboration that randomized 744 depressed individuals aged 60+ with TRD. It is the largest-ever clinical trial of TRD in older adults, with a similar design as the STAR*D and VAST-D studies that were conducted in younger adults. The OPTIMUM trial was a pragmatic trial conducted in the community, using measurement-based care support from the OPTIMUM team to guide patients through treatment. The study found that augmentation with aripiprazole and augmentation with bupropion had roughly similar effectiveness, and were more effective than switch to bupropion; in contrast, all three of these strategies were roughly equal in their risks such as falls and serious adverse events. In the second step of the trial, lithium augmentation and a switch to nortriptyline were roughly equivalent in both effectiveness and risks. After presenting the data on effectiveness and risk from this trial, the symposium speakers will distill these findings into practical recommendations for physicians in treating older adults and describe remaining, unmet challenges in our understanding of TRD treatment in older adults.

Creating a resident-centric rehabilitation research team

BackgroundThe 36-month Physical Medicine and Rehabilitation (PM&R) or Physiatry residency provides a number of multidisciplinary clinical experiences. These experiences often translate to novel research questions, which may not be pursued by residents due to several factors, including limited research exposure and uncertainty of how to begin a project.Limited resident participation in clinical researchnegatively affects the growth of Physiatry as a field and medicine as a whole. Thetwo largest Physiatry organizations – the Association of Academic Physiatristsand the American Academy of Physical Medicine and Rehabilitation – participate inthe Disability and Rehabilitation Research Coalition (DRRC), seeking to improvethe state of rehabilitation and disability research through fundingopportunities by way of the National Institutes of Health (NIH), the NationalInstitute on Disability, Independent Living and Rehabilitation Research(NIDILRR) and the Patient-Centered Outcomes Research Institute (PCORI). Apaucity of new Physiatry researchers neutralizes these efforts.ResultsThis paper detailsthe creation of a novel, multidisciplinary Rehabilitation Resident Researchprogram that promotes resident research culture and production. Mirroring ourcollaborative clinical care paradigm, this program integrates facultymentorship, institutional research collaborates (Neuroscience Nursing ResearchCenter, Neuroscience Research Development Office) and departmental resources(Shark Tank competition) to provide resident-centric research support.ConclusionsThe resident-centricrehabilitation research team has formed a successful research program that waspiloted from the resident perspective, facilitating academic productivity whilerespecting the clinical responsibilities of the 36-month PM&R residency. Residentresearch trainees are uniquely positioned to become future leaders ofmultidisciplinary and multispecialty collaborative teams, with a focus onpatient function and health outcomes.