Patient-Centered Outcomes Research Institute Research Articles

349-P: Hospital Utilization for Hypoglycemia among Patients with Type 2 Diabetes Using Pooled Data from Six Health Systems

Hypoglycemia is the most common serious adverse effect of diabetes treatment and a major cause of medication-related hospitalization. This study aimed to identify trends and predictors of hospital utilization for hypoglycemia among adults with type 2 diabetes. Using electronic health record data from six academic health systems, we performed a retrospective open cohort study including 532,323 patients aged ≥18 years with type 2 diabetes receiving regular care between 2009 and 2019. The primary outcome was the yearly event rate for hypoglycemia hospital utilization: emergency department visits, observation visits, or inpatient admissions for hypoglycemia identified using a validated ICD-9 algorithm. After the transition to ICD-10 in 2015, we used two ICD-10 code sets for hypoglycemia (limited and expanded) that were used in prior studies. We identified independent predictors of hypoglycemia hospital utilization using multivariable logistic regression analysis with data from 2014. We found that yearly rates of hypoglycemia hospital utilization decreased non-significantly from 3.4 to 2.6 events per 1,000 patients from 2009 to 2014. From 2016 to 2019, yearly event rates ranged from 15.5 to 16.5, or 21.1 to 21.8, using the limited and expanded ICD-10 code sets, respectively. The strongest independent risk factors for hypoglycemia hospital utilization were chronic kidney disease (OR 3.13, 95% CI 2.63-3.70), age 18-39 years (OR 3.00 vs. age 40-64 years, 95% CI 2.42-3.73), and insulin use (OR 2.61 vs. no diabetes medications, 95% CI 2.16-3.15). In this multicenter open cohort study, we found that rates of hypoglycemia hospital utilization were stable from 2009 to 2014 and varied considerably by clinical risk factors such that younger adults, insulin users, and those with chronic kidney disease were at especially high risk. There is a need to validate hypoglycemia ascertainment using ICD-10 codes, which detect a substantially higher number of events compared to ICD-9. Disclosure S. J. Pilla: None. J. L. Kraschnewski: None. E. Lehman: None. L. Kong: None. E. Francis: None. J. M. Poger: None. C. L. Bryce: None. N. M. Maruthur: Other Relationship; Self; Johns Hopkins HealthCare Solutions. H. Yeh: None. Funding National Institutes of Health (KL2TR003099); Patient-Centered Outcomes Research Institute (1306-04912)

32-LB: Interstitial Glucose Levels during Exercise in Persons with and without Type 1 Diabetes

Background: Using continuous glucose monitoring (CGM), we investigated potential sex-related differences in glycemia during exercise in persons living with type 1 diabetes (T1D) or without diabetes. Methods: Participants used CGM (Dexcom G6), exercise/meal diaries, or an activity monitor with a meal capture smart phone app, to help identify home based exercise and meal events over a 10 day to 4 wk period. Results: The analyses included 40 T1D (age: 36±15 yrs; BMI: 26.3±3.1 kg/m2; HbA1c: 7.5±1.5%; 35% female; mean±SD) and 120 persons without diabetes (age: 30±20 years; BMI: 24.4±3.2 kg/m2; HbA1c: 5.1±0.3; 64% female) and 283 and 619 exercise events, respectively. The frequency distribution of all CGM values were comparable between males and females overall, but values had a wider distribution among T1D as compared to non-T1D (Fig). Hyperglycemia (> 180 mg/dL) represented ~0.1% of the exercise time in participants without T1D vs. 31% and 24% of the time in the female and male participants without diabetes, respectively. Hypoglycemic values ( Conclusions: Based on CGM, mild hypoglycemic exposure during exercise is surprisingly common in individuals with and without diabetes and may be particularly prevalent in females without diabetes. Disclosure M. Riddell: Advisory Panel; Self; Zealand Pharma A/S. Consultant; Self; Lilly Diabetes. Research Support; Self; Dexcom, Inc., Insulet Corporation. Speaker’s Bureau; Self; Novo Nordisk Inc., Sanofi. Stock/Shareholder; Self; Zucara Therapeutics Inc. Z. Li: None. N. DSouza: None. C. Yeung: None. D. Kesibi: None. S. R. Patton: None. R. Beck: Consultant; Self; Bigfoot Biomedical, Inc., Diasome Pharmaceuticals, Inc., Insulet Corporation, Lilly Diabetes, vTv Therapeutics. Research Support; Self; Beta Bionics, Inc., Dexcom, Inc., Medtronic, Novo Nordisk, Tandem Diabetes Care. P. G. Jacobs: Board Member; Self; Pacific Diabetes Technologies. Research Support; Self; Dexcom, Inc. M. A. Clements: Consultant; Self; Eli Lilly and Company. Employee; Self; Glooko, Inc. Research Support; Self; Abbott Diabetes, Dexcom, Inc. R. L. Gal: None. F. J. Doyle: Advisory Panel; Self; Mode AGC. Other Relationship; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care. C. K. Martin: Advisory Panel; Self; EHE Health. Board Member; Self; NaturallySlim. Research Support; Self; American Society for Nutrition, Leona M. and Harry B. Helmsley Charitable Trust, Lilly, National Institutes of Health, Patient-Centered Outcomes Research Institute, U. S. Department of Agriculture, WW. Other Relationship; Self; ABGIL, Academy of Nutrition and Dietetics. P. Calhoun: None. J. Sherr: Advisory Panel; Self; Cecelia Health, Insulet Corporation, Medtronic. Consultant; Self; Insulet Corporation, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic. Research Support; Self; Dexcom, Inc., Insulet Corporation, Medtronic. Speaker’s Bureau; Self; Lilly Diabetes. J. R. Castle: Advisory Panel; Self; Novo Nordisk, Zealand Pharma A/S. Consultant; Self; ADOCIA. Research Support; Self; Dexcom, Inc. Stock/Shareholder; Spouse/Partner; Insulet Corporation. Stock/Shareholder; Self; Pacific Diabetes Technologies. M. R. Rickels: Advisory Panel; Self; Semma Therapeutics, Sernova, Corp. Research Support; Self; Xeris Pharmaceuticals, Inc.

Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease

BackgroundThe appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy.MethodsUsing an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis.ResultsA total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]).ConclusionsIn this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily. (Funded by the Patient-Centered Outcomes Research Institute; ADAPTABLE ClinicalTrials.gov number, NCT02697916.)

Integrated Digital Health System Tools to Support Decision Making and Treatment Preparation in CKD: The PREPARE NOW Study

Rationale & ObjectiveDigital health system tools to support shared decision making and preparation for kidney replacement treatments for patients with chronic kidney disease (CKD) are needed.Study DesignDescriptive study of the implementation of digital infrastructure to support a patient-centered health system intervention.Setting & Participants4 CKD clinics within a large integrated health system.ExposureWe developed an integrated suite of digital engagement tools to support patients’ shared decision making and preparation for kidney failure treatments. Tools included an automated CKD patient registry and risk prediction algorithm within the electronic health record (EHR) to identify and prioritize patients in need of nurse case management to facilitate shared decision making and preparation for kidney replacement treatments, an electronic patient-facing values clarification tool, a tracking application to document patients’ preparation for treatments, and an EHR work flow to broadcast patients’ treatment preferences to all health care providers.OutcomesUptake and acceptability.Analytic ApproachMixed methods.ResultsFrom July 1, 2017, through June 30, 2018, the CKD registry identified 1,032 patients in 4 nephrology clinics, of whom 243 (24%) were identified as high risk for progressing to kidney failure within 2 years. Kidney Transitions Specialists enrolled 117 (48%) high-risk patients by the end of year 1. The values tool was completed by 30/33 (91%) patients who attended kidney modality education. Nurse case managers used the tracking application for 100% of patients to document 287 planning steps for kidney replacement therapy. Most (87%) high-risk patients had their preferred kidney replacement modality documented and displayed in the EHR. Nurse case managers reported that the tools facilitated their identification of patients needing support and their navigation activities.LimitationsSingle institution, short duration.ConclusionsDigital health system tools facilitated rapid identification of patients needing shared and informed decision making and their preparation for kidney replacement treatments.FundingThis work was supported through a Patient-Centered Outcomes Research Institute (PCORI) Project Program Award (IHS-1409-20967).Trial registrationClinicalTrials.gov NCT02722382.

Associations of quality of social support and beliefs in curability among older adults with advanced cancer.

12049 Background: Prior studies suggest that social support plays a role in disease understanding of older patients with advanced cancer. In this study, we examined the association of quantity and quality of social support with belief in curability among older patients with advanced incurable cancer. Methods: We performed a secondary analysis of a cluster-randomized geriatric assessment trial (URCC 13070: PI Mohile) that recruited older adults (≥70) with advanced incurable cancer and caregivers. At enrollment, patients completed the Older Americans Resources and Services (OARS) Medical Social Support form to measure both quantity (number of close friends and relatives) and quality of social support. Quality of social support was measured using twelve questions, each ranged from 1 (none of the time) to 5 (all of the time). Higher cumulative scores indicated greater quality of support. For beliefs in curability, patients were asked, “What do you believe are the chances that your cancer will go away and never come back with treatment?” Responses were 0%, <50%, 50/50, >50%, and 100%. Ordinal logistic regression was used to investigate the association of social support with beliefs in curability, adjusting for adjusting for age, gender, education, race, number of Geriatric Assessment (GA) impairments, cancer type, and locality (rural versus urban). Results: We included 347 patients; mean age was 76.4 years, 91% were white, 52% were male, 46% had household income <$50,000, and 55% had high school degree or higher. For every unit increase in OARS Medical Social Support score, the odds of believing in curability decreases by 36.4% [Adjusted Odds Ratio (AOR) 0.733, 95% Confidence Interval (CI): (0.555, 0.969)], after controlling for covariates. Quantity of social support was not associated with belief in curability [AOR 1.033 95% CI: (0.921, 1.156)]. Conclusions: Our study revealed that older patients with advanced cancer who felt more supported by their social network were more likely to report that their cancer was not curable. Interventions that improve quality of social support may also affect disease understanding. Funding: Patient-Centered Outcomes Research Institute (PCORI) 4634 and NIH K24 AG056589 to SGM, NCI UG1CA189961, T32CA102618, NCI K99CA237744 to Loh.

Comparing the Effectiveness of Education Versus Digital Cognitive Behavioral Therapy for Adults With Sickle Cell Disease: Protocol for the Cognitive Behavioral Therapy and Real-time Pain Management Intervention for Sickle Cell via Mobile Applications (CaRISMA) Study.

BackgroundPatients with sickle cell disease (SCD) experience significant medical and psychological stressors that affect their mental health, well-being, and disease outcomes. Digital cognitive behavioral therapy (CBT) has been used in other patient populations and has demonstrated clinical benefits. Although evidence-based, nonpharmacological interventions for pain management are widely used in other populations, these treatments have not been well studied in SCD. Currently, there are no adequately powered large-scale clinical trials to evaluate the effectiveness and dissemination potential of behavioral pain management for adults with SCD. Furthermore, some important details regarding behavioral therapies in SCD remain unclear—in particular, what works best for whom and when.ObjectiveOur primary goal is to compare the effectiveness of two smartphone–delivered programs for reducing SCD pain symptoms: digital CBT versus pain and SCD education (Education). Our secondary goal is to assess whether baseline depression symptoms moderate the effect of interventions on pain outcomes. We hypothesize that digital CBT will confer greater benefits on pain outcomes and depressive symptoms at 6 months and a greater reduction in health care use (eg, opioid prescriptions or refills or acute care visits) over 12 months.MethodsThe CaRISMA (Cognitive Behavioral Therapy and Real-time Pain Management Intervention for Sickle Cell via Mobile Applications) study is a multisite comparative effectiveness trial funded by the Patient-Centered Outcomes Research Institute. CaRISMA is conducted at six clinical academic sites, in partnership with four community-based organizations. CaRISMA will evaluate the effectiveness of two 12-week health coach–supported digital health programs with a total of 350 participants in two groups: CBT (n=175) and Education (n=175). Participants will complete a series of questionnaires at baseline and at 3, 6, and 12 months. The primary outcome will be the change in pain interference between the study arms. We will also evaluate changes in pain intensity, depressive symptoms, other patient-reported outcomes, and health care use as secondary outcomes. We have 80% power to detect a difference of 0.37 SDs between study arms on 6-month changes in the outcomes with 15% expected attrition at 6 months. An exploratory analysis will examine whether baseline depression symptoms moderate the effect of the intervention on pain interference.ResultsThis study will be conducted from March 2021 through February 2022, with results expected to be available in February 2023.ConclusionsPatients with SCD experience significant disease burden, psychosocial stress, and impairment of their quality of life. CaRISMA proposes to leverage digital technology and overcome barriers to the routine use of behavioral treatments for pain and depressive symptoms in the treatment of adults with SCD. The study will provide data on the comparative effectiveness of digital CBT and Education approaches and evaluate the potential for implementing evidence-based behavioral interventions to manage SCD pain.Trial RegistrationClinicalTrials.gov NCT04419168; https://clinicaltrials.gov/ct2/show/NCT04419168.International Registered Report Identifier (IRRID)PRR1-10.2196/29014

Spotlight commentary: A role for real-world evidence to inform the clinical care of patients with diabetes mellitus.

Spotlight commentary: A role for real-world evidence to inform the clinical care of patients with diabetes mellitus.

723 Sleep Apnea Care During the COVID-19 Pandemic: Perspectives on the Transition to Telemedicine from Clinicians and Patients

IntroductionCovid-19-related public health control measures have necessitated a rapid transition in healthcare delivery. We qualitatively explored clinicians’ and patients’ experiences of the pandemic’s impact on the delivery and receipt of obstructive sleep apnea (OSA) care.MethodsBetween September and December 2020, we conducted ten 90-minute virtual focus groups with sleep clinicians (n=19) and English and Spanish-speaking patients with OSA (n= 30) recruited through an urban academic sleep clinic, national organizations, social media, and snowball sampling. An interdisciplinary team conducted a rapid qualitative analysis that included prefigured and emergent domains. The team developed a comprehensive analytic matrix, identifying key themes within and between groups and triangulating them across participant types.ResultsClinicians and patients across all groups confirmed a rapid shift to the adoption of telemedicine. Clinicians reported telemedicine enhanced evaluations by enabling direct observation of the home environment, providing opportunities to guide patients on medical equipment used in the home, and cultivating meaningful social connections for patients. Perceived benefits varied across patient subgroups (age, language, technological self-efficacy). The majority of clinicians reported that telemedicine’s initial uptake resulted in delays in care and revenue loss, but sustained use was thought to be feasible over time. Patients reported delays in care related to the pandemic’s disruption on healthcare and their personal safety concerns. Additionally, telemedicine’s adoption directly altered other elements of care, including the delivery of patient education materials and loss of tacit information gained during the in-person visit. All groups reported adequate mask fitting as a central challenge for patients using positive airway pressure therapy. Spanish-speaking patients noted concerns of increased difficulty accessing care and navigating the OSA care system due to limited English proficiency, in addition to the limited availability of OSA resources in Spanish.ConclusionDuring the Covid-19 pandemic, the rapid adoption of telemedicine largely facilitated OSA care but altered patient-clinician interactions, delivery of patient education materials, and mask fitting success. Given that telemedicine will likely be sustained post-pandemic, there are needs for targeted efforts aimed at addressing disparities in telemedicine, enhancing practitioner telepresence and education, and new approaches for mask fitting to ensure successful OSA care.Support (if any)Patient-Centered Outcomes Research Institute EADI-16493

Identifying Treatment Effect Moderators in the TARGET Trial: A Secondary Analysis

The purpose of this secondary analysis was to identify treatment effect moderators from a large, pragmatic, cluster randomized trial for prevention of chronic low back pain (LBP). The TARGET trial was conducted at 76 primary care clinics in 4 health systems across the United States between May 2016 and June 2018. Practices were randomly assigned (1:1) to stratified care (intervention) or usual care (control). The intervention included identifying high risk patients with acute LBP and triggering an electronic best practice alert for referral for psychologically informed physical therapy (PIPT). We estimated and compared average Oswestry Disability Questionnaire (ODQ) scores at 6 months using linear mixed models controlling for baseline ODQ scores with site (fixed effects) and clinic (random effects) to account for cluster randomization. Baseline factors were considered treatment effect moderators if the type III test for the treatment x factor interaction resulted in a p-value ≤0.15. These analyses included 1,250 patients with completed baseline data and 6-month ODQ scores. Baseline characteristics were (Intervention, Control respectively): under 45 years of age (44%, 43%), female (61%, 62%), White (81%, 74%), non-Hispanic (91%, 92%), obese (50%, 48%), and non-smoking (65%, 68%). Potential effect modifiers were pain medication and smoking (p's ≤ 0.15). The intervention group had larger 6 month ODQ improvement for patients taking ≥3 pain medications, (7.0 points, P = 0.05) and current smokers (5.7 points, P = 0.02). In the TARGET trial smoking and taking ≥3 pain medications were patient level factors related to larger ODQ improvements from PIPT. The magnitude of improvements did not exceed clinically meaningful thresholds, however these factors still could be used to tailor receipt of PIPT treatment. These findings add to the existing treatment moderation literature for LBP but need to confirmed in additional trials. Patient-Centered Outcomes Research Institute (PCORI) contract # PCS-1402-10867. The purpose of this secondary analysis was to identify treatment effect moderators from a large, pragmatic, cluster randomized trial for prevention of chronic low back pain (LBP). The TARGET trial was conducted at 76 primary care clinics in 4 health systems across the United States between May 2016 and June 2018. Practices were randomly assigned (1:1) to stratified care (intervention) or usual care (control). The intervention included identifying high risk patients with acute LBP and triggering an electronic best practice alert for referral for psychologically informed physical therapy (PIPT). We estimated and compared average Oswestry Disability Questionnaire (ODQ) scores at 6 months using linear mixed models controlling for baseline ODQ scores with site (fixed effects) and clinic (random effects) to account for cluster randomization. Baseline factors were considered treatment effect moderators if the type III test for the treatment x factor interaction resulted in a p-value ≤0.15. These analyses included 1,250 patients with completed baseline data and 6-month ODQ scores. Baseline characteristics were (Intervention, Control respectively): under 45 years of age (44%, 43%), female (61%, 62%), White (81%, 74%), non-Hispanic (91%, 92%), obese (50%, 48%), and non-smoking (65%, 68%). Potential effect modifiers were pain medication and smoking (p's ≤ 0.15). The intervention group had larger 6 month ODQ improvement for patients taking ≥3 pain medications, (7.0 points, P = 0.05) and current smokers (5.7 points, P = 0.02). In the TARGET trial smoking and taking ≥3 pain medications were patient level factors related to larger ODQ improvements from PIPT. The magnitude of improvements did not exceed clinically meaningful thresholds, however these factors still could be used to tailor receipt of PIPT treatment. These findings add to the existing treatment moderation literature for LBP but need to confirmed in additional trials. Patient-Centered Outcomes Research Institute (PCORI) contract # PCS-1402-10867.

Lessons Learned from Developing Plain Language Summaries of Research Studies.

Background:Plain language translation may facilitate the public's ability to understand and use results of scientific research.Brief description of activity:This article describes the Patient-Centered Outcomes Research Institute's (PCORI) approach to and lessons learned from developing plain language summaries of PCORI-funded research for the lay public.Implementation:We developed and tested a standard template for the summaries, incorporating feedback in the template design from focus groups with members of the public. Between February 2017 and March 2020, we completed translation of 272 plain language summaries of PCORI-funded studies, covering topics including cardiovascular disease, obesity, cancer, mental health, asthma, HIV/AIDS, and comparative effectiveness research methods.Results:Templates use a question-and-answer format, with sections on the rationale, methods, results, limitations, and how the research will help inform decisions. In addition to feedback on template heading wording and order, focus group participants stressed the importance of establishing relevance and conveying credibility and limitations.Lessons learned:Lessons learned relate to supporting consistency across individual summaries, carefully prioritizing content to include in the summaries, and balancing plain language and reading level with precision. These lessons learned from template development and implementation may be useful to other organizations or publishers contemplating similar efforts to make scientific research results more accessible. [HLRP: Health Literacy Research and Practice. 2021;5(2):e155–e161.]Plain Language Summary:The Patient-Centered Outcomes Research Institute (PCORI) funds comparative effectiveness research. This research compares the benefits and harms of two or more health care choices. In this article, we describe lessons learned from PCORI's efforts to develop plain language summaries of results from the research it funds. These lessons may help other organizations that want to share research results in plain language.

Palliative Care and Parkinson's Disease: Time to Move Beyond Cancer.

Movement DisordersVolume 36, Issue 6 p. 1325-1329 Viewpoint Palliative Care and Parkinson's Disease: Time to Move Beyond Cancer Benzi M. Kluger MD, MS, Corresponding Author benzi_kluger@urmc.rochester.edu Departments of Neurology and Medicine, University of Rochester Medical Center, Rochester, New York, USA Correspondence to: Prof. Benzi M. Kluger, Departments of Neurology and Medicine, University of Rochester Medical Center, 265 Crittenden Blvd, Box CU 420694, Rochester, NY 14618, USA; E-mail: benzi_kluger@urmc.rochester.eduSearch for more papers by this authorRachel Dolhun MD, The Michael J. Fox Foundation, New York, New York, USASearch for more papers by this authorMalenna Sumrall PhD, Parkinson Foundation Patient and Family Advisory Council, New York, New York, USASearch for more papers by this authorKirk Hall MBA, Parkinson Foundation Patient and Family Advisory Council, New York, New York, USASearch for more papers by this authorMichael S. Okun MD, Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida, USA Parkinson's Foundation, Miami, Florida, USASearch for more papers by this author Benzi M. Kluger MD, MS, Corresponding Author benzi_kluger@urmc.rochester.edu Departments of Neurology and Medicine, University of Rochester Medical Center, Rochester, New York, USA Correspondence to: Prof. Benzi M. Kluger, Departments of Neurology and Medicine, University of Rochester Medical Center, 265 Crittenden Blvd, Box CU 420694, Rochester, NY 14618, USA; E-mail: benzi_kluger@urmc.rochester.eduSearch for more papers by this authorRachel Dolhun MD, The Michael J. Fox Foundation, New York, New York, USASearch for more papers by this authorMalenna Sumrall PhD, Parkinson Foundation Patient and Family Advisory Council, New York, New York, USASearch for more papers by this authorKirk Hall MBA, Parkinson Foundation Patient and Family Advisory Council, New York, New York, USASearch for more papers by this authorMichael S. Okun MD, Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida, USA Parkinson's Foundation, Miami, Florida, USASearch for more papers by this author First published: 30 March 2021 https://doi.org/10.1002/mds.28556 Relevant conflicts of interest/financial disclosures:: B.M.K. has received research grant support from the National Institute of Aging, National Institute of Nursing Research, and Patient-Centered Outcomes Research Institute; he has received speaker honoraria from the Parkinson's Foundation. R.D. has nothing to report. M.S. has received support as a care partner stakeholder from the Patient-Centered Outcomes Research Institute. K.H. has received support as a patient stakeholder from the Patient-Centered Outcomes Research Institute. M.S.O. serves as a consultant for the Parkinson's Foundation and has received research grants from the NIH, Parkinson's Foundation, The Michael J. Fox Foundation, the Parkinson Alliance, Smallwood Foundation, the Bachmann-Strauss Foundation, the Tourette Syndrome Association, and the UF Foundation. M.S.O.'s deep brain stimulation research is supported by NIH grants R01 NR014852 and R01 NS096008. M.S.O. is the primary investigator (PI) of the NIH R25NS108939 Training Grant; has received royalties for publications with Demos, Manson, Amazon, Smashwords, Books4Patients, Perseus, Robert Rose, Oxford, and Cambridge (movement disorders books); is an associate editor for New England Journal of Medicine Journal Watch Neurology; has participated in Continuing Medical Education and educational activities on movement disorders sponsored by the Academy for Healthcare Learning, PeerView, Prime, QuantiaMD, WebMD/Medscape, Medicus, MedNet, Einstein, MedNet, Henry Stewart, American Academy of Neurology, Movement Disorders Society, and Vanderbilt University. The institution and not M.S.O. receives grants from Medtronic, AbbVie, Boston Scientific, Abbott, and Allergan, and the PI has no financial interest in these grants. M.S.O. has participated as a site PI and/or coinvestigator for several NIH-, foundation-, and industry-sponsored trials over the years but has not received honoraria. Research projects at the University of Florida receive device and drug donations. Full financial disclosures and author roles may be found in the online version of this article. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Volume36, Issue6June 2021Pages 1325-1329 RelatedInformation

The Effect of Different National Treatment Strategies on Disability Outcome in Relapsing-Remitting Multiple Sclerosis: A Propensity Score Adjusted Comparison between Denmark and Sweden

Background: Treatment strategies for relapsing-remitting multiple sclerosis (RRMS) vary markedly between Denmark and Sweden. The objective was to investigate the influence of such differences on disease modifying treatment (DMT) and disability outcome. Methods: Patients with RRMS commencing their first DMT 2013-2016 were retrospectively included from the Swedish and Danish MS registries. Time to the 24-week confirmed disability worsening (CDW, primary outcome) and 24-week confirmed disability improvement (CDI, secondary outcome) and milestone expanded disability status scale (EDSS) score 3 and 4 end-points (secondary outcomes) were analyzed using Inverse Probability of Treatment Weighting (IPTW)-based Cox regression models with robust standard errors. The IPTW model used a propensity score to weight and correct the comparison for the imbalance of confounders observed at baseline between the two countries. Findings: A total of 2700 patients from the Swedish registry and 2161 patients from the Danish MS registry commencing a first DMT between 2013 and 2016 were included in the analysis and observed for an average of 4 years. The proportion of patients initiating with a low-moderate as compared to highly effective DMT was 92.4% (teriflunomide 42%) and 7.6% in Denmark and 62.4% (teriflunomide 2.4%) and 35% in Sweden, respectively. Swedish patients were associated with a 29% reduction in the rate of post-baseline 24-week CDW relative to Danish patients (IPTW HR 0.71; 95% CI 0.57-0.90; p=0.004). The Swedish cohort was associated with a 27% and 26% reduction in the rate of reaching EDSS 3 and 4 respectively, relative to Danish patients (HR 0.73; 95% CI 0.62-0.85; p<0.001; and 0.74; 95% CI 0.59-0.93; p=0.009, reference = Denmark). Interpretation: We show for the first time that differences in treatment strategies of RRMS have an impact on disability outcomes at a national level. Escalation of treatment efficacy seemed inferior to using more efficacious DMT as initial treatment. Funding Statement: This study was supported by the Swedish Research Council, the Swedish Brain foundation, the Karolinska University Hospital & the Patient-Centered Outcomes Research Institute (PCORI), the Swedish Multiple Sclerosis Research Foundation, the Swedish Federal Government (LUA/ALF Agreement ALFGBG-722081), the Swedish Association of Persons with Neurological Disabilities, the Research Foundation of the Multiple Sclerosis Society of Gothenburg, the Edit Jacobson Foundation, and NEURO Sweden. Declaration of Interests: TS has received compensation for serving on scientific advisory boards, honoraria for consultancy and funding for travel from Biogen Inc; speaker honoraria from Novartis. MM has served on scientific advisory board for Biogen, Sanofi, Roche, Novartis, Merck, Abbvie, has received honoraria for lecturing from Biogen, Merck, Novartis, Sanofi, Genzyme, has received research support and support for congress participation from Biogen, Genzyme, Roche, Merck, Novartis. FP has received research grants from Biogen and Novartis. AS reports no conflicts of interest FS has served on scientific advisory boards for, served as consultant for, received support for congress participation or received speaker honoraria from Alexion, Biogen, Merck, Novartis, Roche and Sanofi Genzyme. His laboratory has received research support from Biogen, Merck, Novartis, Roche and Sanofi Genzyme. PVR has served on scientific advisory board for Biogen, Sanofi, Roche, Novartis, Merck, and Alexion, has received honoraria for lecturing from Biogen, Merck, Novartis, Roche, has received support for congress participation from Biogen, Genzyme, Roche, Merck, Novartis. MK reports no conflicts of interest HJ has received honoraria for participating in advisory board from Biogen. JH has received honoraria for serving on advisory boards for Biogen, Sanofi-Genzyme and Novartis and speaker’s fees from Biogen, Novartis, Merck-Serono, Bayer-Schering, Teva and Sanofi-Genzyme. He has served as P.I. for projects, or received unrestricted research support from, BiogenIdec, Merck- Serono, TEVA, Sanofi-Genzyme and Bayer-Schering. His MS research is funded by the Swedish Research Council and the Swedish Brain foundation JL has received travel support and/or lecture honoraria from Biogen, Novartis, Merck, Alexion, Roche and SanofiGenzyme; has served on scientific advisory boards for Biogen, Novartis, Merck, Roche, BSM and SanofiGenzyme; serves on the editorial board of the Acta Neurologica Scandinavica; has received unconditional research grants from Biogen, and Novartis. Ethics Approval Statement: The study was approved by the The Swedish Ethical Review Authority (Dnr: 2019-00839/1199-18), and The Danish Data Protection Authority (Org. number 202100 2973).

Optimizing Outcomes of Treatment - Resistant Depression in Older Adults (OPTIMUM): Study Design and Sample

<h3>Introduction</h3> Late-life treatment resistant depression (LLTRD) is common in older adults as many fail to respond to first-line pharmacotherapies such as SSRIs and SNRIs. LLTRD is associated with deleterious effects as it leads to worsening of medical outcomes, increased disability, and worsening of cognitive dysfunction. Thus, there remains a need to determine more effective and safer treatments for LLTRD. Next line treatments, including augmentation strategies (e.g., with aripiprazole, bupropion, or lithium) or switching to a tricyclic antidepressant have not been studied systematically in older adults. OPTIMUM is a pragmatic randomized clinical trial (RCT) in which we compared strategies of augmentation vs switching in older adults (60 years and older) with TRD in a five- center collaborative study funded by the Patient-Centered Outcomes Research Institute (PCORI). OPTIMUM compared the effectiveness and risks of several strategies using a two-step protocol. <h3>Methods</h3> Participants were recruited and randomized if they were 60 years and older, met the <i>Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition</i> (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 antidepressants being different from the medications being tested in OPTIMUM). Upon study entry, participants either continued their index antidepressant, if assigned to augmentation, or tapered it off, if assigned to switching. Randomization occurred in two steps, with each step lasting 10 weeks. In Step 1, 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 Depression Rating Scale (MADRS) after ten weeks of treatment. Those who do not remit (defined as a MADRS score <10) proceed to Step 2 where they were randomized to either lithium augmentation of an index antidepressant or switching to nortriptyline. <h3>Results</h3> Step 1 involved 621 participants, of which 212 were randomized to augmentation with aripiprazole, 206 to augmentation with bupropion, and 203 to a switch to bupropion. Of these 621 Step-1 participants, 269 (43%) were >70 years, 415 (67%) were female, and 98 (16%) were non-Caucasian. Step 2 involved 251 participants of which 127 were randomized to augmentation to augmentation with lithium and 124 to a switch to nortriptyline. Of these 251 Step-2 participants, 104 (41%) were >70 years, 176 (70%) were female, and 26 (10%) were non-Caucasian. <h3>Conclusions</h3> OPTIMUM is a pragmatic RCT comparing the effectiveness, tolerability, and safety of several augmentation and switch strategies in a large and diverse group of patients with LLTRD. The study responds to the need of clinicians and patients to make treatment decisions and improve the quality of life of their patients with LLTRD based on evidence on the benefits and risks of commonly used treatment options. <h3>Funding</h3> This research was funded through a Patient-Centered Outcomes Research Institute (PCORI) award TRD-1511- 33321.

A Prognostic Tool for COVID-19 Decision Support: The Intermountain Risk Score Predicts Major Adverse Health Events in Patients Positive for COVID-19

Background: As the COVID-19 pandemic evolves, stratifying risk is increasingly important. The Intermountain Risk Score (IMRS) uses the complete blood count (CBC) and basic metabolic profile (BMP) as a first-line predictor of mortality and is widely validated. We hypothesized that IMRS predicts COVID-19 outcomes.Methods: Intermountain Healthcare patients aged ≥18 years were evaluated if they had CBC and BMP measured in 2019 and tested positive for COVID-19 in 2020. Viral RNA testing for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was conducted March 3 through November 2, 2020. IMRS used published sex-specific weightings and associations were evaluated for the composite of COVID-19 hospitalization or mortality.Findings: Among 3,883 patients, 8.2% were hospitalized, 1.6% died. Subjects with low, mild, moderate, and high-risk IMRS had the composite endpoint in 3.5% (52/1,502), 8.6% (108/1,256), 15.5% (152/979), and 28.1% (41/146), respectively. Versus low-risk, subjects in mild, moderate, and high-risk groups had HR=2.33 (95% CI: 1.67, 3.24), HR=4.01 (CI: 2.93, 5.50), and HR=8.34 (CI: 5.54, 12.57), respectively. Subjects aged Interpretation: IMRS, a simple risk score using very basic laboratory results, predicted COVID-19 hospitalization and mortality. This included important abilities to identify risk in younger adults with few diagnosed comorbidities and to predict risk prior to SARS-CoV-2 infection.Funding Statement: This study was funded by internal Intermountain departmental funds.Declaration of Interests: BDH, HTM, BSR, and JLA are inventors of clinical decision tools that are licensed to CareCentra and Alluceo. BDH is the PI of grants related to clinical decision tools that were funded by Intermountain Healthcare’s Foundry innovation program, the Intermountain Research and Medical Foundation, CareCentra, GlaxoSmithKline, and AstraZeneca. BDH is a member of the scientific advisory board of Labme.ai. KUK is PI of and BDH a co-investigator of a grant funded by the Patient- Centered Outcomes Research Institute (PCORI). IDP was supported by a grant from the National Institute of General Medical Sciences (K23GM129661). Outside the current work, IDP has received grant support from the National Institutes of Health, Centers for Disease Control, Janssen Pharmaceuticals, and Immunexpress Inc and funding to his institution from Regeneron Pharmaceuticals. The authors have no other potential conflicts of interest to report.Ethics Approval Statement: This study was approved as a data-only historical records review study with a waiver of consent by the Intermountain Healthcare Institutional Review Board.

FP02.08 Importance of Stakeholder Engagement in a Patient-Centered Outcomes Research Trial

The Watch the Spot Trial is a Patient-Centered Outcomes Research Institute (PCORI)- funded, multi-center, pragmatic, comparative effectiveness trial comparing a more- versus less-intensive surveillance strategies for small lung nodules. As a PCORI-funded study, engagement with patients and other stakeholders is an essential aspect of the Watch the Spot Trial. A key component, the Stakeholder Advisory Group (SAG), provides oversight and guidance regarding research methodology, publications, communications, survey development and recruitment, and dissemination of study results.

21614 Use of an Outcomes Continuum to Describe Disparities in CVOID-19: Data from the OneFlorida Research Consortium

ABSTRACT IMPACT: Identifying differential COVID-19 progression across the disease continuum may help policymakers and service providers better identify or predict gaps in services and resources and develop precision strategies to support COVID-19 patients where the need is mostly needed. OBJECTIVES/GOALS: Single institution studies have documented COVID-19 disproportionally affected US racial and ethnic minority groups compared to Whites. However, few population-wide data studied severity and death in multiracial populations. We aim to examine the current disparity in the COVID-19 continuum, including hospitalizations, severity, and death. METHODS/STUDY POPULATION: Data on 67,094 laboratory documented COVID-19 cases nested from the state-wide ‘OneFlorida’ research consortium through August 3, 2020, were assessed to decide differences and disparities in COVID-19 outcomes. A COVID-19 outcome continuum outlining the proportions of cases transitioning from diagnosis to death was constructed (Figure 1). OneFlorida partners provide health care to more than 40% of Floridians in the nation’s third-largest and very diverse state. OneFlorida partners encompass hospitals, practice/clinic settings, and physicians, which provide care for 15 million patients across all of Florida’s 67 counties. It is part of the Patient-Centered Outcomes Research Institute (PCORI). RESULTS/ANTICIPATED RESULTS: Among cases, 25,443 (37.9%) were non-Hispanic Whites, 11,709 (17.5%) were non-Hispanic Blacks, and 16,119 (24.0%) were Hispanics. Among COVID-19 patients, Blacks and Hispanics had a higher frequency of emergency department (ED) visits (45.7% and 46.0%, respectively), whereas admission rates were higher in Blacks (15.6%) and Whites (15.9%) than in Hispanics (11.5%). Blacks had the highest rates of intubation (3.6%) and in-hospital deaths (2.7%) compared to Whites (2.5% and 2.3%, respectively) and Hispanics (1.3% and 1.4%, respectively), Figure 1. When rates were indexed to the state census data, Blacks had the worst rates across the disease continuum (infection to death). In comparison, Hispanics had higher rates of ED visits but lower rates of intubation and death, Table 1. DISCUSSION/SIGNIFICANCE OF FINDINGS: Outcomes continuum is a useful tool at an individual-level to assess care outcomes and at population-level as a framework to analyze the proportion of population with COVID-19 that progress to each successive disease stage. This will help policymakers to better identify gaps in services and develop precision strategies to support COVID-19 patients.

Web Exclusive. Annals On Call - Pregnancy, Lactation, and the COVID-19 Vaccines.

Web ExclusivesMarch 2021Annals On Call - Pregnancy, Lactation, and the COVID-19 VaccinesFREERobert M. Centor, MD and Laura E. Riley, MDRobert M. Centor, MDHuntsville Regional Medical Campus, University of Alabama Birmingham School of Medicine, Birmingham, Alabama (R.M.C.)Search for more papers by this author and Laura E. Riley, MDWeill Cornell School of Medicine, New York, New York (L.E.R.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/A20-0009 CME/MOC SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In this episode of Annals On Call, Dr. Centor discusses the current recommendations for COVID-19 vaccination in women who are pregnant or considering pregnancy with Dr. Laura E. Riley from Weill Cornell School of Medicine.Annals articles discussed include...Inclusion of Pregnant and Lactating Persons in COVID-19 Vaccination Efforts: https://www.acpjournals.org/doi/10.7326/M21-0173About Annals On CallAnnals On Call focuses on a clinically influential article published in Annals of Internal Medicine. Dr. Robert Centor shares his own perspective on the material and interviews topic area experts to discuss, debate, and share diverse insights about patient care and health care delivery.For more information on Annals On Call and for more episodes, visit go.annals.org/OnCall. Comments0 CommentsSign In to Submit A Comment Raphael Stricker, MDUnion Square Medical Associates23 February 2021 Pre-Exposure Prophylaxis for COVID-19 in Pregnant Women Alternative to experimental COVID vaccines in pregnancy: https://www.dovepress.com/articles.php?article_id=61495 Author, Article, and Disclosure InformationAffiliations: Huntsville Regional Medical Campus, University of Alabama Birmingham School of Medicine, Birmingham, Alabama (R.M.C.)Weill Cornell School of Medicine, New York, New York (L.E.R.)Disclosures: Dr. Centor has disclosed the following: Consultancy: DynaMed, MDCalc. Employment: U.S. Department of Veterans Affairs. Dr. Riley has disclosed the following: Royalties: UpToDate. Honoraria: GlaxoSmithKline. Other: Contemporary OB-GYN MAVEN.Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Stephanie Chang, MD, MPH, Deputy Editor, reports employment with the Agency for Healthcare Research and Quality, travel compensation from the Guidelines International Network, and participation in the Patient-Centered Outcomes Research Institute methodology committee. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interests to disclose. Eliseo Guallar, MD, MPH, DrPH, Deputy Editor, Statistics, reports that he has no financial relationships or interests to disclose. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.This article was published at Annals.org on 23 February 2021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoInclusion of Pregnant and Lactating Persons in COVID-19 Vaccination Efforts Laura E. Riley and Denise J. Jamieson Metrics Cited byISIDOG Consensus Guidelines on COVID-19 Vaccination for Women before, during and after Pregnancy March 2021Volume 174, Issue 3Page: OC2 ePublished: 23 February 2021 Issue Published: March 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.Loading ...

Evaluating performance of covariate-constrained randomization (CCR) techniques under misspecification of cluster-level variables in cluster-randomized trials

Covariate constrained randomization (CCR) is a method of controlling imbalance in important baseline covariates in cluster-randomized trials (CRT). We use simulated CRTs to investigate the performance (control of imbalance) of CCR relative to simple randomization (SR) under conditions of misspecification of the cluster-level variable used in the CCR algorithm.We use data from a Patient-Centered Outcomes Research Institute (PCORI)-funded CRT evaluating the Mothers and Babies (MB) intervention (AD-1507-31,473). CCR methodology was used in the MB study to control imbalance in, among other baseline variables, the percent minority (i.e., non-White) participants at each study site. Simulation schemes explored variation in degree of misspecification in the baseline covariate of interest, and include correct report, observed misspecification, and a range of simulated misspecification for intervals within and beyond that observed in the MB study. We also consider three within-site sample size scenarios: that observed in the MB study, small (mean 10) and large (mean 50). Simulations at every level of baseline covariate misspecification suggest that use of the CCR strategy provides between-arm imbalance that is simultaneously lower and less variable, on average, than that produced from the SR strategy. We find that the gains to using CCR over SR are nearly twice as high with accurate reporting (Δ = −5.33) compared to the observed study-level misspecification (Δ = −3.03). Although CCR still outperforms SR as the level of misspecification increases, the gains to using CCR over SR decrease; thus, every effort should still be made to obtain high-quality baseline data.

Partnering to Increase Colorectal Cancer Screening: Perspectives of Community Advisory Board Members.

The Patient-Centered Outcomes Research Institute (PCORI) defines engagement in research as the meaningful involvement of patients, caregivers, clinicians, insurers, and others throughout the entire research process-from planning to conducting the study to disseminating study results. The purposes of this paper are to (a) describe methods used to engage community members across the various phases of a PCORI-funded comparative effectiveness trial to increase colorectal cancer screening; and (b) report results of qualitative and quantitative evaluations of community advisory board members' experiences on this project. Decisions to join and stay engaged with the study included feeling valued and appreciated, being compensated, the opportunity to contribute to research based on their skills and expertise, and being committed to colon cancer prevention efforts. Challenges identified by advisory board members included the significant time commitment, transportation, and meeting location. Lessons learned and guidance for researchers committed to patient and community engagement are described.

Associations Between Experience of Early Childhood Trauma and Impact on Obesity Status, Health, as Well as Perceptions of Obesity-Related Health Care

ObjectiveTo evaluate the association between obesity and history of childhood trauma in an effort to define implications for the provider-patient relationship and possible causes of failure of obesity treatment. MethodsMultisite survey developed by the Patient-Centered Outcomes Research Institute Learning Health Systems Obesity Cohort Workgroup consisting of 49 questions with 2 questions focusing on history of being a victim of childhood physical and/or sexual abuse was mailed to 19,964 overweight or obese patients. Data collection for this survey occurred from October 27, 2017, through March 1, 2018. ResultsAmong the 2211 surveys included in analysis, respondents reporting being a victim of childhood abuse increased significantly with obesity (23.6%, 26.0%, 29.1%, and 36.8% for overweight, class I, class II, and class III obesity, respectively; P<.001). A higher percentage of those who reported being a victim of childhood abuse noted that their weight issues began at an earlier age (P=.002) and were more likely to have weight-related comorbidities (P<.001), even after controlling for body mass index. Impacting physician counseling on weight loss, patients who were childhood victims of abuse reported lower self-esteem (P<.001), were more likely to feel judged by their health care providers (P=.009), and less likely to feel being treated with respect (P=.045). ConclusionOverall, being a victim of childhood abuse was significantly associated with obesity, lower self-esteem and negative experiences interacting with health care providers. Health care providers should receive training to ensure open and nonjudgmental visits with obese patients and consider the role of trauma survivorship issues in patients’ development of obesity and health care experiences.