Evaluating analytic models for individually randomized group treatment trials with complex clustering in nested and crossed designs.

Many individually randomized group treatment (IRGT) trials randomly assign individuals to study arms but deliver treatments via shared agents, such as therapists, surgeons, or trainers. Post-randomization interactions induce correlations in outcome measures between participants sharing the same agent. Agents can be nested in or crossed with trial arm, and participants may interact with a single agent or with multiple agents. These complications have led to ambiguity in choice of models but there have been no systematic efforts to identify appropriate analytic models for these study designs. To address this gap, we undertook a simulation study to examine the performance of candidate analytic models in the presence of complex clustering arising from multiple membership, single membership, and single agent settings, in both nested and crossed designs and for a continuous outcome. With nested designs, substantial type I error rate inflation was observed when analytic models did not account for multiple membership and when analytic model weights characterizing the association with multiple agents did not match the data generating mechanism. Conversely, analytic models for crossed designs generally maintained nominal type I error rates unless there was notable imbalance in the number of participants that interact with each agent.

Reducing Central Nervous System-Active Medications to Prevent Falls and Injuries Among Older Adults: A Cluster Randomized Clinical Trial.

Importance: High-risk medications that contribute to adverse health outcomes are frequently prescribed to older adults. Deprescribing interventions reduce their use, but studies are often not designed to examine effects on patient-relevant health outcomes. Objective: To test the effect of a health system-embedded deprescribing intervention targeting older adults and their primary care clinicians for reducing the use of central nervous system-active drugs and preventing medically treated falls. Design, Setting, and Participants: In this cluster randomized, parallel-group, clinical trial, 18 primary care practices from an integrated health care delivery system in Washington state were recruited from April 1, 2021, to June 16, 2022, to participate, along with their eligible patients. Randomization occurred at the clinic level. Patients were community-dwelling adults aged 60 years or older, prescribed at least 1 medication from any of 5 targeted medication classes (opioids, sedative-hypnotics, skeletal muscle relaxants, tricyclic antidepressants, and first-generation antihistamines) for at least 3 consecutive months. Intervention: Patient education and clinician decision support. Control arm participants received usual care. Main Outcomes and Measures: The primary outcome was medically treated falls. Secondary outcomes included medication discontinuation, sustained medication discontinuation, and dose reduction of any and each target medication. Serious adverse drug withdrawal events involving opioids or sedative-hypnotics were the main safety outcome. Analyses were conducted using intent-to-treat analysis. Results: Among 2367 patient participants (mean [SD] age, 70.6 [7.6] years; 1488 women [63%]), the adjusted cumulative incidence rate of a first medically treated fall at 18 months was 0.33 (95% CI, 0.29-0.37) in the intervention group and 0.30 (95% CI, 0.27-0.34) in the usual care group (estimated adjusted hazard ratio, 1.11 (95% CI, 0.94-1.31) (P = .11). There were significant differences favoring the intervention group in discontinuation, sustained discontinuation, and dose reduction of tricyclic antidepressants at 6 months (discontinuation adjusted rate: intervention group, 0.23 [95% CI, 0.18-0.28] vs usual care group, 0.13 [95% CI, 0.09-0.17]; adjusted relative risk, 1.79 [95% CI, 1.29-2.50]; P = .001) and secondary time points (9, 12, and 15 months). Conclusions and Relevance: In this randomized clinical trial of a health system-embedded deprescribing intervention targeting community-dwelling older adults prescribed central nervous system-active medications and their primary care clinicians, the intervention was no more effective than usual care in reducing medically treated falls. For health systems that attend to deprescribing as part of routine clinical practice, additional interventions may confer modest benefits on prescribing without a measurable effect on clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT05689554.

Residential Density Is Associated With BMI Trajectories in Children and Adolescents: Findings From the Moving to Health Study.

Introduction: This study investigates the associations between built environment features and 3-year BMI trajectories in children and adolescents. Methods: This retrospective cohort study utilized electronic health records of individuals aged 5-18 years living in King County, Washington, from 2005 to 2017. Built environment features such as residential density; counts of supermarkets, fast-food restaurants, and parks; and park area were measured using SmartMaps at 1,600-meter buffers. Linear mixed-effects models performed in 2022 tested whether built environment variables at baseline were associated with BMI change within age cohorts (5, 9, and 13 years), adjusting for sex, age, race/ethnicity, Medicaid, BMI, and residential property values (SES measure). Results: At 3-year follow-up, higher residential density was associated with lower BMI increase for girls across all age cohorts and for boys in age cohorts of 5 and 13 years but not for the age cohort of 9 years. Presence of fast food was associated with higher BMI increase for boys in the age cohort of 5 years and for girls in the age cohort of 9 years. There were no significant associations between BMI change and counts of parks, and park area was only significantly associated with BMI change among boys in the age cohort of 5 years. Conclusions: Higher residential density was associated with lower BMI increase in children and adolescents. The effect was small but may accumulate over the life course. Built environment factors have limited independent impact on 3-year BMI trajectories in children and adolescents.

Sitting Time Reduction and Blood Pressure in Older Adults: A Randomized Clinical Trial.

Importance: Practical health promotion strategies for improving cardiometabolic health in older adults are needed. Objective: To examine the efficacy of a sedentary behavior reduction intervention for reducing sitting time and improving blood pressure in older adults. Design, Setting, and Participants: This parallel-group randomized clinical trial was conducted in adults aged 60 to 89 years with high sitting time and body mass index of 30 to 50 from January 1, 2019, to November 31, 2022, at a health care system in Washington State. Intervention: Participants were randomized 1:1 to the sitting reduction intervention or a healthy living attention control condition for 6 months. Intervention participants received 10 health coaching contacts, sitting reduction goals, and a standing desk and fitness tracker to prompt sitting breaks. The attention control group received 10 health coaching contacts to set general healthy living goals, excluding physical activity or sedentary behavior. Main Outcomes and Measures: The primary outcome, measured at baseline, 3 months, and 6 months, was sitting time assessed using accelerometers worn for 7 days at each time point. Coprimary outcomes were systolic and diastolic blood pressure measured at baseline and 6 months. Results: A total of 283 participants (140 intervention and 143 control) were randomized (baseline mean [SD] age, 68.8 [6.2] years; 186 [65.7%] female; mean [SD] body mass index, 34.9 [4.7]). At baseline, 147 (51.9%) had a hypertension diagnosis and 97 (69.3%) took at least 1 antihypertensive medication. Sitting time was reduced, favoring the intervention arm, with a difference in the mean change of -31.44 min/d at 3 months (95% CI, -48.69 to -14.19 min/d; P < .001) and -31.85 min/d at 6 months (95% CI, -52.91 to -10.79 min/d; P = .003). Systolic blood pressure change was lower by 3.48 mm Hg, favoring the intervention arm at 6 months (95% CI, -6.68 to -0.28 mm Hg; P = .03). There were 6 serious adverse events in each arm and none were study related. Conclusions and Relevance: In this study of a 6-month sitting reduction intervention, older adults in the intervention reduced sedentary time by more than 30 min/d and reduced systolic blood pressure. Sitting reduction could be a promising approach to improve health in older adults. Trial Registration: ClinicalTrials.gov Identifier: NCT03739762.

Neighborhood built and food environment in relation to glycemic control in people with type 2 diabetes in the moving to health study.

OBJECTIVE: To examine whether built environment and food metrics are associated with glycemic control in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: We included 14,985 patients with type 2 diabetes using electronic health records from Kaiser Permanente Washington. Patient addresses were geocoded with ArcGIS using King County and Esri reference data. Built environment exposures estimated from geocoded locations included residential unit density, transit threshold residential unit density, park access, and having supermarkets and fast food restaurants within 1600-m Euclidean buffers. Linear mixed effects models compared mean changes of HbA1c from baseline at 1, 3 (primary) and 5 years by each built environment variable. RESULTS: Patients (mean age = 59.4 SD = 13.2, 49.5% female, 16.6% Asian, 9.8% Black, 5.5% Latino/Hispanic, 57.1% White, 20% insulin dependent, mean BMI = 32.7±7.7) had an average of 6 HbA1c measures available. Participants in the 1st tertile of residential density (lowest) had a greater decline in HbA1c (-0.42, -0.43, and -0.44 in years 1, 3, and 5 respectively) than those in the 3rd tertile (HbA1c = -0.37 at 1- and 3-years and -0.36 at 5-years; all p-values <0.05). Having any supermarkets within 1600 m of home was associated with a greater decrease in HbA1c at 1-year and 3-years compared to having none (all p-values <0.05). CONCLUSIONS: Lower residential density and better proximity to supermarkets may benefit HbA1c control in people with people with type 2 diabetes. However, effects were small and indicate limited clinical significance.

Evaluating tests for cluster-randomized trials with few clusters under generalized linear mixed models with covariate adjustment: A simulation study.

Generalized linear mixed models (GLMM) are commonly used to analyze clustered data, but when the number of clusters is small to moderate, standard statistical tests may produce elevated type I error rates. Small-sample corrections have been proposed for continuous or binary outcomes without covariate adjustment. However, appropriate tests to use for count outcomes or under covariate-adjusted models remains unknown. An important setting in which this issue arises is in cluster-randomized trials (CRTs). Because many CRTs have just a few clusters (eg, clinics or health systems), covariate adjustment is particularly critical to address potential chance imbalance and/or low power (eg, adjustment following stratified randomization or for the baseline value of the outcome). We conducted simulations to evaluate GLMM-based tests of the treatment effect that account for the small (10) or moderate (20) number of clusters under a parallel-group CRT setting across scenarios of covariate adjustment (including adjustment for one or more person-level or cluster-level covariates) for both binary and count outcomes. We find that when the intraclass correlation is non-negligible ( ≥ $$ \ge $$ 0.01) and the number of covariates is small ( ≤ $$ \le $$ 2), likelihood ratio tests with a between-within denominator degree of freedom have type I error rates close to the nominal level. When the number of covariates is moderate ( ≥ $$ \ge $$ 5), across our simulation scenarios, the relative performance of the tests varied considerably and no method performed uniformly well. Therefore, we recommend adjusting for no more than a few covariates and using likelihood ratio tests with a between-within denominator degree of freedom.

Engaging staff to improve COVID-19 vaccination response at long-term care facilities (ENSPIRE): A cluster randomized trial of co-designed, tailored vaccine promotion materials.

BACKGROUND: COVID-19 vaccination rates among long-term care center (LTCC) workers are among the lowest of all frontline health care workers. Current efforts to increase COVID-19 vaccine uptake generally focus on strategies that have proven effective for increasing influenza vaccine uptake among health care workers including educational and communication strategies. Experimental evidence is lacking on the comparative advantage of educational strategies to improve vaccine acceptance and uptake, especially in the context of COVID-19. Despite the lack of evidence, education and communication strategies are recommended to improve COVID-19 vaccination rates and decrease vaccine hesitancy (VH), especially strategies using tailored messaging for disproportionately affected populations. METHODS: We describe a cluster-randomized comparative effectiveness trial with 40 LTCCs and approximately 4000 LTCC workers in 2 geographically, culturally, and ethnically distinct states. We compare the effectiveness of two strategies for increasing COVID-19 booster vaccination rates and willingness to promote COVID-19 booster vaccination: co-design processes for tailoring educational messages vs. an enhanced usual care comparator. Our study focuses on the language and/or cultural groups that are most disproportionately affected by VH and low COVID-19 vaccine uptake in these LTCCs. CONCLUSION: Finding effective methods to increase COVID-19 vaccine uptake and decrease VH among LTCC staff is critical. Beyond COVID-19, better approaches are needed to improve vaccine uptake and decrease VH for a variety of existing vaccines as well as vaccines created to address novel viruses as they emerge.

Considerations for Subgroup Analyses in Cluster-Randomized Trials Based on Aggregated Individual-Level Predictors.

In research assessing the effect of an intervention or exposure, a key secondary objective often involves assessing differential effects of this intervention or exposure in subgroups of interest; this is often referred to as assessing effect modification or heterogeneity of treatment effects (HTE). Observed HTE can have important implications for policy, including intervention strategies (e.g., will some patients benefit more from intervention than others?) and prioritizing resources (e.g., to reduce observed health disparities). Analysis of HTE is well understood in studies where the independent unit is an individual. In contrast, in studies where the independent unit is a cluster (e.g., a hospital or school) and a cluster-level outcome is used in the analysis, it is less well understood how to proceed if the HTE analysis of interest involves an individual-level characteristic (e.g., self-reported race) that must be aggregated at the cluster level. Through simulations, we show that only individual-level models have power to detect HTE by individual-level variables; if outcomes must be defined at the cluster level, then there is often low power to detect HTE by the corresponding aggregated variables. We illustrate the challenges inherent to this type of analysis in a study assessing the effect of an intervention on increasing COVID-19 booster vaccination rates at long-term care centers.

STRategies to Improve Pain and Enjoy life (STRIPE): results of a pragmatic randomized trial of pain coping skills training and opioid medication taper guidance for patients on long-term opioid therapy.

ABSTRACT: Because long-term opioid therapy (LtOT) for chronic pain has uncertain benefits and dose-dependent harms, safe and effective strategies for opioid tapering are needed. Adapting a promising pilot study intervention, we conducted the STRategies to Improve Pain and Enjoy life (STRIPE) pragmatic clinical trial. Patients in integrated health system on moderate-to-high dose of LtOT for chronic noncancer pain were randomized individually to usual care plus intervention (n = 79) or usual care only (n = 74). The intervention included pain coping skills training and optional support for opioid taper, delivered in 18 telephone sessions over a year, with pharmacologic guidance provided to participants' primary care providers by a pain physician. Coprimary outcomes were daily opioid dose (morphine milligram equivalent [MME]), calculated using pharmacy dispensing data, and the self-reported Pain, Enjoyment of Life and General Activity scale at 12 months (primary time point) and 6 months. Secondary outcomes included opioid misuse, opioid difficulties, opioid craving, pain self-efficacy, and global impression of change, depression, and anxiety. Only 41% randomized to the intervention completed all sessions. We did not observe significant differences between intervention and usual care for MME (adjusted mean difference: -2.3 MME; 95% confidence interval: -10.6, 5.9; P = 0.578), the Pain, Enjoyment of Life, General Activity scale (0.0 [95% confidence interval: -0.5, 0.5], P = 0.985), or most secondary outcomes. The intervention did not lower opioid dose or improve pain or functioning. Other strategies are needed to reduce opioid doses while improving pain and function for patients who have been on LtOT for years with high levels of medical, mental health, and substance use comorbidity.

A health-system-embedded deprescribing intervention targeting patients and providers to prevent falls in older adults (STOP-FALLS trial): study protocol for a pragmatic cluster-randomized controlled trial.

BACKGROUND: Central nervous system (CNS) active medications have been consistently linked to falls in older people. However, few randomized trials have evaluated whether CNS-active medication reduction reduces falls and fall-related injuries. The objective of the Reducing CNS-active Medications to Prevent Falls and Injuries in Older Adults (STOP-FALLS) trial is to test the effectiveness of a health-system-embedded deprescribing intervention focused on CNS-active medications on the incidence of medically treated falls among community-dwelling older adults. METHODS: We will conduct a pragmatic, cluster-randomized, parallel-group, controlled clinical trial within Kaiser Permanente Washington to test the effectiveness of a 12-month deprescribing intervention consisting of (1) an educational brochure and self-care handouts mailed to older adults prescribed one or more CNS-active medications (aged 60 + : opioids, benzodiazepines and Z-drugs; aged 65 + : skeletal muscle relaxants, tricyclic antidepressants, and antihistamines) and (2) decision support for their primary health care providers. Outcomes are examined over 18-26 months post-intervention. The primary outcome is first incident (post-baseline) medically treated fall as determined from health plan data. Our sample size calculations ensure at least 80% power to detect a 20% reduction in the rate of medically treated falls for participants receiving care within the intervention (n = 9) versus usual care clinics (n = 9) assuming 18 months of follow-up. Secondary outcomes include medication discontinuation or dose reduction of any target medications. Safety outcomes include serious adverse drug withdrawal events, unintentional overdose, and death. We will also examine medication signetur fields for attempts to decrease medications. We will report factors affecting implementation of the intervention. DISCUSSION: The STOP-FALLS trial will provide new information about whether a health-system-embedded deprescribing intervention that targets older participants and their primary care providers reduces medically treated falls and CNS-active medication use. Insights into factors affecting implementation will inform future research and healthcare organizations that may be interested in replicating the intervention. TRIAL REGISTRATION: ClinicalTrial.gov NCT05689554. Registered on 18 January 2023, retrospectively registered.

Comparing the clinical and cost-effectiveness of remote (telehealth and online) cognitive behavioral therapy-based treatments for high-impact chronic pain relative to usual care: study protocol for the RESOLVE multisite randomized control trial.

BACKGROUND: Cognitive behavioral therapy for chronic pain (CBT-CP) is an effective but underused treatment for high-impact chronic pain. Increased access to CBT-CP services for pain is of critical public health importance, particularly for rural and medically underserved populations who have limited access due to these services being concentrated in urban and high income areas. Making CBT-CP widely available and more affordable could reduce barriers to CBT-CP use. METHODS: As part of the National Institutes of Health Helping to End Addiction Long-term® (NIH HEAL) initiative, we designed and implemented a comparative effectiveness, 3-arm randomized control trial comparing remotely delivered telephonic/video and online CBT-CP-based services to usual care for patients with high-impact chronic pain. The RESOLVE trial is being conducted in 4 large integrated healthcare systems located in Minnesota, Georgia, Oregon, and Washington state and includes demographically diverse populations residing in urban and rural areas. The trial compares (1) an 8-session, one-on-one, professionally delivered telephonic/video CBT-CP program; and (2) a previously developed and tested 8-session online CBT-CP-based program (painTRAINER) to (3) usual care augmented by a written guide for chronic pain management. Participants are followed for 1 year post-allocation and are assessed at baseline, and 3, 6, and 12 months post-allocation. The primary outcome is minimal clinically important difference (MCID; ≥ 30% reduction) in pain severity (composite of pain intensity and pain-related interference) assessed by a modified 11-item version of the Brief Pain Inventory-Short Form at 3 months. Secondary outcomes include pain severity, pain intensity, and pain-related interference scores, quality of life measures, and patient global impression of change at 3, 6, and 12 months. Cost-effectiveness is assessed by incremental cost per additional patient with MCID in primary outcome and by cost per quality-adjusted life year achieved. Outcome assessment is blinded to group assignment. DISCUSSION: This large-scale trial provides a unique opportunity to rigorously evaluate and compare the clinical and cost-effectiveness of 2 relatively low-cost and scalable modalities for providing CBT-CP-based treatments to persons with high-impact chronic pain, including those residing in rural and other medically underserved areas with limited access to these services. TRIAL REGISTRATION: ClinicalTrials.gov NCT04523714. This trial was registered on 24 August 2020.

Acupuncture for chronic low back pain in older adults: Design and protocol for the BackInAction pragmatic clinical trial.

BACKGROUND: Back pain prevalence and burden increase with age; approximately one-third of U.S. adults 65 years of age and older experience lower back pain (LBP). For chronic low back pain (cLBP), typically defined as lasting three months or longer, many treatments for younger adults may be inappropriate for older adults given their greater prevalence of comorbidities with attendant polypharmacy. While acupuncture has been demonstrated to be safe and effective for cLBP in adults overall, few studies of acupuncture have either included or focused on adults ≥65 years old. METHODS: The BackInAction study is a pragmatic, multi-site, three-arm, parallel-groups randomized controlled trial designed to test the effectiveness of acupuncture needling for improving back pain-related disability among 807 older adults ≥65 years old with cLBP. Participants are randomized to standard acupuncture (SA; up to 15 treatment sessions across 12 weeks), enhanced acupuncture (EA; SA during first 12 weeks and up to 6 additional sessions across the following 12 weeks), and usual medical care (UMC) alone. Participants are followed for 12 months with study outcomes assessed monthly with the primary outcome timepoint at 6 months. DISCUSSION: The BackInAction study offers an opportunity to further understand the effectiveness, dose-dependence, and safety of acupuncture in a Medicare population. Additionally, study results may encourage broader adoption of more effective, safer, and more satisfactory options to the continuing over-reliance on opioid- and invasive medical treatments for cLBP among older adults. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04982315. Clinical trial registration date: July 29, 2021.

Acceptability and Adherence to Home, Kiosk, and Clinic Blood Pressure Measurement Compared to 24-H Ambulatory Monitoring.

BACKGROUND: The US Preventive Services Task Force recommends measuring blood pressure (BP) outside of clinic/office settings. While various options are available, including home devices, BP kiosks, and 24-h ambulatory BP monitoring (ABPM), understanding patient acceptability and adherence is a critical factor for implementation. OBJECTIVE: To compare the acceptability and adherence of clinic, home, kiosk, and ABPM measurement. DESIGN: Comparative diagnostic accuracy study which randomized adults to one of three BP measurement arms: clinic, home, and kiosk. ABPM was conducted on all participants. PARTICIPANTS: Adults (18-85 years) receiving care at 12 Kaiser Permanente Washington primary care clinics (Washington State, USA) with a high BP (≥ 138 mmHg systolic or ≥ 88 mmHg diastolic) in the electronic health record with no hypertension diagnosis and on no hypertensive medications and with high BP at a research screening visit. MEASURES: Patient acceptability was measured using a validated survey which was used to calculate an overall acceptability score (range 1-7) at baseline, after completing their assigned BP measurement intervention, and after completing ABPM. Adherence was defined based on the pre-specified number of BP measurements completed. KEY RESULTS: Five hundred ten participants were randomized (mean age 59 years), with mean BP of 150/88. Overall acceptability score was highest (i.e. most acceptable) for Home BP (mean 6.2, SD 0.7) and lowest (least acceptable) for ABPM (mean 5.0, SD 1.0); scores were intermediate for Clinic (5.5, SD 1.1) and Kiosk (5.4, SD 1.0). Adherence was higher for Home (154/170, 90.6%) and Clinic (150/172, 87.2%) than for Kiosk (114/168, 67.9%)). The majority of participants (467/510, 91.6%) were adherent to ABPM. CONCLUSIONS: Participants found home BP measurement most acceptable followed by clinic, BP kiosks, and ABPM. Our findings, coupled with recent evidence regarding the accuracy of home BP measurement, further support the routine use of home-based BP measurement in primary care practice in the US. TRIAL REGISTRATION: ClinicalTrials.gov NCT03130257 https://clinicaltrials.gov/ct2/show/NCT03130257.

Moderators and Nonspecific Predictors of Treatment Benefits in a Randomized Trial of Mindfulness-Based Stress Reduction vs Cognitive-Behavioral Therapy vs Usual Care for Chronic Low Back Pain.

Both mindfulness-based stress reduction (MBSR) and cognitive-behavioral therapy (CBT) are effective for chronic low back pain (CLBP), but little is known regarding who might benefit more from one than the other. Using data from a randomized trial comparing MBSR, CBT, and usual care (UC) for adults aged 20 to 70 years with CLBP (N = 297), we examined baseline characteristics that moderated treatment effects or were associated with improvement regardless of treatment. Outcomes included 8-week function (modified Roland Disability Questionnaire), pain bothersomeness (0-10 numerical rating scale), and depression (Patient Health Questionnaire-8). There were differences in the effects of CBT versus MBSR on pain based on participant gender (P = .03) and baseline depressive symptoms (P = .01), but the only statistically significant moderator after Bonferroni correction was the nonjudging dimension of mindfulness. Scores on this measure moderated the effects of CBT versus MBSR on both function (P = .001) and pain (P = .04). Pain control beliefs (P <.001) and lower anxiety (P < .001) predicted improvement regardless of treatment. Replication of these findings is needed to guide treatment decision-making for CLBP. TRIAL REGISTRATION: The trial and analysis plan were preregistered in ClinicalTrials.gov (Identifier: NCT01467843). PERSPECTIVE: Although few potential moderators and nonspecific predictors of benefits from CBT or MBSR for CLBP were statistically significant after adjustment for multiple comparisons, these findings suggest potentially fruitful directions for confirmatory research while providing reassurance that patients could reasonably expect to benefit from either treatment.

Active Postlicensure Safety Surveillance for Recombinant Zoster Vaccine Using Electronic Health Record Data.

Recombinant zoster vaccine (RZV) (Shingrix; GlaxoSmithKline, Brentford, United Kingdom) is an adjuvanted glycoprotein vaccine that was licensed in 2017 to prevent herpes zoster (shingles) and its complications in older adults. In this prospective, postlicensure Vaccine Safety Datalink study using electronic health records, we sequentially monitored a real-world population of adults aged ≥50 years who received care in multiple US Vaccine Safety Datalink health systems to identify potentially increased risks of 10 prespecified health outcomes, including stroke, anaphylaxis, and Guillain-Barré syndrome (GBS). Among 647,833 RZV doses administered from January 2018 through December 2019, we did not detect a sustained increased risk of any monitored outcome for RZV recipients relative to either historical (2013-2017) recipients of zoster vaccine live, a live attenuated virus vaccine (Zostavax; Merck & Co., Inc., Kenilworth, New Jersey), or contemporary non-RZV vaccine recipients who had an annual well-person visit during the 2018-2019 study period. We confirmed prelicensure trial findings of increased risks of systemic and local reactions following RZV. Our study provides additional reassurance about the overall safety of RZV. Despite a large sample, uncertainty remains regarding potential associations with GBS due to the limited number of confirmed GBS cases that were observed.

Preoperative Depression Status and 5 Year Metabolic and Bariatric Surgery Outcomes in the PCORnet Bariatric Study Cohort.

OBJECTIVE: To examine whether depression status before metabolic and bariatric surgery (MBS) influenced 5-year weight loss, diabetes, and safety/utilization outcomes in the PCORnet Bariatric Study. SUMMARY OF BACKGROUND DATA: Research on the impact of depression on MBS outcomes is inconsistent with few large, long-term studies. METHODS: Data were extracted from 23 health systems on 36,871 patients who underwent sleeve gastrectomy (SG; n=16,158) or gastric bypass (RYGB; n=20,713) from 2005-2015. Patients with and without a depression diagnosis in the year before MBS were evaluated for % total weight loss (%TWL), diabetes outcomes, and postsurgical safety/utilization (reoperations, revisions, endoscopy, hospitalizations, mortality) at 1, 3, and 5 years after MBS. RESULTS: 27.1% of SG and 33.0% of RYGB patients had preoperative depression, and they had more medical and psychiatric comorbidities than those without depression. At 5 years of follow-up, those with depression, versus those without depression, had slightly less %TWL after RYGB, but not after SG (between group difference = 0.42%TWL, P = 0.04). However, patients with depression had slightly larger HbA1c improvements after RYGB but not after SG (between group difference = - 0.19, P = 0.04). Baseline depression did not moderate diabetes remission or relapse, reoperations, revision, or mortality across operations; however, baseline depression did moderate the risk of endoscopy and repeat hospitalization across RYGB versus SG. CONCLUSIONS: Patients with depression undergoing RYGB and SG had similar weight loss, diabetes, and safety/utilization outcomes to those without depression. The effects of depression were clinically small compared to the choice of operation.

Provider knowledge, beliefs, and self-efficacy to deprescribe opioids and sedative-hypnotics.

BACKGROUND: While many studies have assessed and measured patient attitudes toward deprescribing, less quantitative research has addressed the provider perspective. We thus sought to describe provider knowledge, beliefs, and self-efficacy to deprescribe, with a focus on opioids and sedative-hypnotics. METHODS: An electronic anonymous survey was distributed to primary care providers at Kaiser Permanente Washington. Two reminder emails were sent. The survey included 10 questions on general deprescribing, and six questions each specific to opioid and sedative-hypnotic deprescribing. Knowledge questions used a multiple-choice response option format. Questions addressing beliefs and self-efficacy (i.e., confidence) used a 0-10 Likert scale. Scales were dichotomized at ≥7 to define agreement (belief questions) or confidence (self-efficacy questions). We calculated descriptive statistics to summarize the responses. RESULTS: Of 370 eligible primary care providers, 95 (26%) completed the survey. For general deprescribing questions, a majority believed that lack of patient willingness, withdrawal symptoms and fear of symptom return, and time constraints impeded deprescribing. Approximately half chose the correct answers about opioid deprescribing, 21% were confident that they could alleviate patient concerns about opioid tapering, and 32% were confident managing chronic non-cancer pain without opioids. For sedative-hypnotics, 64%-87% of respondents correctly answered questions about risks and the relative effectiveness of alternatives, but only one-third correctly answered a question about sedative-hypnotic tapering. Roughly half were confident in their ability to successfully engage patients in sedative deprescribing conversations and select alternatives. Only 54% and 34% were confident in writing a tapering protocol for opioids and sedative-hypnotics, respectively. CONCLUSION: Results suggest that raising provider awareness of patient willingness to deprescribe, addressing knowledge gaps, and increasing self-efficacy for deprescribing are important targets for improving deprescribing. Support for writing tapering protocols and prescribing evidence-based drug and non-drug alternatives may be important to improve care.

Comparative Safety and Effectiveness of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy for Weight Loss and Type 2 Diabetes Across Race and Ethnicity in the PCORnet Bariatric Study Cohort.

Importance: Bariatric surgery is the most effective treatment for severe obesity; yet it is unclear whether the long-term safety and comparative effectiveness of these operations differ across racial and ethnic groups. Objective: To compare outcomes of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) across racial and ethnic groups in the National Patient-Centered Clinical Research Network (PCORnet) Bariatric Study. Design, Setting, and Participants: This was a retrospective, observational, comparative effectiveness cohort study that comprised 25 health care systems in the PCORnet Bariatric Study. Patients were adults and adolescents aged 12 to 79 years who underwent a primary (first nonrevisional) RYGB or SG operation between January 1, 2005, and September 30, 2015, at participating health systems. Patient race and ethnicity included Black, Hispanic, White, other, and unrecorded. Data were analyzed from July 1, 2021, to January 17, 2022. Exposure: RYGB or SG. Outcomes: Percentage total weight loss (%TWL); type 2 diabetes remission, relapse, and change in hemoglobin A1c (HbA1c) level; and postsurgical safety and utilization outcomes (operations, interventions, revisions/conversions, endoscopy, hospitalizations, mortality, 30-day major adverse events) at 1, 3, and 5 years after surgery. Results: A total of 36 871 patients (mean [SE] age, 45.0 [11.7] years; 29 746 female patients [81%]) were included in the weight analysis. Patients identified with the following race and ethnic categories: 6891 Black (19%), 8756 Hispanic (24%), 19 645 White (53%), 826 other (2%), and 783 unrecorded (2%). Weight loss and mean reductions in HbA1c level were larger for RYGB than SG in all years for Black, Hispanic, and White patients (difference in 5-year weight loss: Black, -7.6%; 95% CI, -8.0 to -7.1; P < .001; Hispanic, -6.2%; 95% CI, -6.6 to -5.9; P < .001; White, -5.9%; 95% CI, -6.3 to -5.7; P < .001; difference in change in year 5 HbA1c level: Black, -0.29; 95% CI, -0.51 to -0.08; P = .009; Hispanic, -0.45; 95% CI, -0.61 to -0.29; P < .001; and White, -0.25; 95% CI, -0.40 to -0.11; P = .001.) The magnitude of these differences was small among racial and ethnic groups (1%-3% of %TWL). Black and Hispanic patients had higher risk of hospitalization when they had RYGB compared with SG (hazard ratio [HR], 1.45; 95% CI, 1.17-1.79; P = .001 and 1.48; 95% CI, 1.22-1.79; P < .001, respectively). Hispanic patients had greater risk of all-cause mortality (HR, 2.41; 95% CI, 1.24-4.70; P = .01) and higher odds of a 30-day major adverse event (odds ratio, 1.92; 95% CI, 1.38-2.68; P < .001) for RYGB compared with SG. There was no interaction between race and ethnicity and operation type for diabetes remission and relapse. Conclusions and Relevance: Variability of the comparative effectiveness of operations for %TWL and HbA1c level across race and ethnicity was clinically small; however, differences in safety and utilization outcomes were clinically and statistically significant for Black and Hispanic patients who had RYGB compared with SG. These findings can inform shared decision-making regarding bariatric operation choice for different racial and ethnic groups of patients.

Associations between neighborhood built environment, residential property values, and adult BMI change: The Seattle Obesity Study III.

Objective: To examine associations between neighborhood built environment (BE) variables, residential property values, and longitudinal 1- and 2-year changes in body mass index (BMI). Methods: The Seattle Obesity Study III was a prospective cohort study of adults with geocoded residential addresses, conducted in King, Pierce, and Yakima Counties in Washington State. Measured heights and weights were obtained at baseline (n = 879), year 1 (n = 727), and year 2 (n = 679). Tax parcel residential property values served as proxies for individual socioeconomic status. Residential unit and road intersection density were captured using Euclidean-based SmartMaps at 800 m buffers. Counts of supermarket (0 versus. 1+) and fast-food restaurant availability (0, 1-3, 4+) were measured using network based SmartMaps at 1600 m buffers. Density measures and residential property values were categorized into tertiles. Linear mixed-effects models tested whether baseline BE variables and property values were associated with differential changes in BMI at year 1 or year 2, adjusting for age, gender, race/ethnicity, education, home ownership, and county of residence. These associations were then tested for potential disparities by age group, gender, race/ethnicity, and education. Results: Road intersection density, access to food sources, and residential property values were inversely associated with BMI at baseline. At year 1, participants in the 3rd tertile of density metrics and with 4+ fast-food restaurants nearby showed less BMI gain compared to those in the 1st tertile or with 0 restaurants. At year 2, higher residential property values were predictive of lower BMI gain. There was evidence of differential associations by age group, gender, and education but not race/ethnicity. Conclusion: Inverse associations between BE metrics and residential property values at baseline demonstrated mixed associations with 1- and 2-year BMI change. More work is needed to understand how individual-level sociodemographic factors moderate associations between the BE, property values, and BMI change.