Heart failure subtype after acute kidney injury.

INTRODUCTION: Acute kidney injury (AKI) is associated with increased risk of heart failure (HF). Determining the type of HF experienced by AKI survivors (heart failure with preserved or reduced ejection fraction, HFpEF or HFrEF) could suggest potential mechanisms underlying the association and opportunities for improving post-AKI care. METHODS: In this retrospective study of adults within the Vanderbilt University health system with a diagnosis of HF, we tested whether AKI events in the two years preceding incident HF associated more with HFpEF or HFrEF while controlling for known predictors. HF outcomes were defined by administrative codes and classified as HFpEF or HFrEF by echocardiogram data. We used multivariable logistic regression models to estimate the effects of AKI on the odds of incident HFpEF versus HFrEF. RESULTS: AKI (all stages) trended towards a preferential association with HFpEF in adjusted analyses (adjusted OR 0.80, 95% CI 0.63 - 1.01). Stage 1 AKI was associated with higher odds of HFpEF that was statistically significant (adjusted OR 0.62, 95% CI 0.43 - 0.88), whereas stages 2-3 AKI showed a trend toward HFrEF that did not reach statistical significance (adjusted OR 1.11, 95% CI 0.76 - 1.63). CONCLUSIONS: AKI as a binary outcome trended towards a preferential association with HFpEF. Stage 1 AKI was associated with higher odds of HFpEF, whereas stage 2-3 trended towards an association with HFrEF that did not meet statistical significance. Different mechanisms may predominate in incident HF following mild versus more severe AKI. Close follow-up with particular attention to volume status and cardiac function after discharge is warranted after even mild AKI.

Impact of Helicobacter pylori Infection and Treatment on Colorectal Cancer in a Large, Nationwide Cohort.

PURPOSE: Helicobacter pylori is the most common cause of infection-associated cancer worldwide. We aimed to evaluate the impact of H. pylori infection and treatment on colorectal cancer (CRC) incidence and mortality. PATIENTS: US Veterans who completed H. pylori testing between 1999 and 2018. METHODS: We conducted a retrospective cohort analysis among adults within the Veterans Health Administration who completed testing for H. pylori. The primary exposures were (1) H. pylori test result (positive/negative) and (2) H. pylori treatment (untreated/treated) among H. pylori-positive individuals. The primary outcomes were CRC incidence and mortality. Follow-up started at the first H. pylori testing and continued until the earliest of incident or fatal CRC, non-CRC death, or December 31, 2019. RESULTS: Among 812,736 individuals tested for H. pylori, 205,178 (25.2%) tested positive. Being H. pylori-positive versus H. pylori-negative was associated with higher CRC incidence and mortality. H. pylori treatment versus no treatment was associated with lower CRC incidence and mortality (absolute risk reduction 0.23%-0.35%) through 15-year follow-up. Being H. pylori-positive versus H. pylori-negative was associated with an 18% (adjusted hazard ratio [adjusted HR], 1.18 [95% CI, 1.12 to 1.24]) and 12% (adjusted HR, 1.12 [95% CI, 1.03 to 1.21]) higher incident and fatal CRC risk, respectively. Individuals with untreated versus treated H. pylori infection had 23% (adjusted HR, 1.23 [95% CI, 1.13 to 1.34]) and 40% (adjusted HR, 1.40 [95% CI, 1.24 to 1.58]) higher incident and fatal CRC risk, respectively. The results were more pronounced in the analysis restricted to individuals with nonserologic testing. CONCLUSION: H. pylori positivity may be associated with small but statistically significant higher CRC incidence and mortality; untreated individuals, especially those with confirmed active infection, appear to be most at risk.

The Goldilocks Dilemma on Balancing User Response and Reflection in mHealth Interventions: Observational Study.

Background: Mobile health (mHealth) has the potential to radically improve health behaviors and quality of life; however, there are still key gaps in understanding how to optimize mHealth engagement. Most engagement research reports only on system use without consideration of whether the user is reflecting on the content cognitively. Although interactions with mHealth are critical, cognitive investment may also be important for meaningful behavior change. Notably, content that is designed to request too much reflection could result in users' disengagement. Understanding how to strike the balance between response burden and reflection burden has critical implications for achieving effective engagement to impact intended outcomes. Objective: In this observational study, we sought to understand the interplay between response burden and reflection burden and how they impact mHealth engagement. Specifically, we explored how varying the response and reflection burdens of mHealth content would impact users' text message response rates in an mHealth intervention. Methods: We recruited support persons of people with diabetes for a randomized controlled trial that evaluated an mHealth intervention for diabetes management. Support person participants assigned to the intervention (n=148) completed a survey and received text messages for 9 months. During the 2-year randomized controlled trial, we sent 4 versions of a weekly, two-way text message that varied in both reflection burden (level of cognitive reflection requested relative to that of other messages) and response burden (level of information requested for the response relative to that of other messages). We quantified engagement by using participant-level response rates. We compared the odds of responding to each text and used Poisson regression to estimate associations between participant characteristics and response rates. Results: The texts requesting the most reflection had the lowest response rates regardless of response burden (high reflection and low response burdens: median 10%, IQR 0%-40%; high reflection and high response burdens: median 23%, IQR 0%-51%). The response rate was highest for the text requesting the least reflection (low reflection and low response burdens: median 90%, IQR 61%-100%) yet still relatively high for the text requesting medium reflection (medium reflection and low response burdens: median 75%, IQR 38%-96%). Lower odds of responding were associated with higher reflection burden (P<.001). Younger participants and participants who had a lower socioeconomic status had lower response rates to texts with more reflection burden, relative to those of their counterparts (all P values were <.05). Conclusions: As reflection burden increased, engagement decreased, and we found more disparities in engagement across participants' characteristics. Content encouraging moderate levels of reflection may be ideal for achieving both cognitive investment and system use. Our findings provide insights into mHealth design and the optimization of both engagement and effectiveness.

Interaction between Continuous Pack-Years Smoked and Polygenic Risk Score on Lung Cancer Risk: Prospective Results from the Framingham Heart Study.

BACKGROUND: Lung cancer risk attributable to smoking is dose dependent, yet few studies examining a polygenic risk score (PRS) by smoking interaction have included comprehensive lifetime pack-years smoked. METHODS: We analyzed data from participants of European ancestry in the Framingham Heart Study Original (n = 454) and Offspring (n = 2,470) cohorts enrolled in 1954 and 1971, respectively, and followed through 2018. We built a PRS for lung cancer using participant genotyping data and genome-wide association study summary statistics from a recent study in the OncoArray Consortium. We used Cox proportional hazards regression models to assess risk and the interaction between pack-years smoked and genetic risk for lung cancer adjusting for European ancestry, age, sex, and education. RESULTS: We observed a significant submultiplicative interaction between pack-years and PRS on lung cancer risk (P = 0.09). Thus, the relative risk associated with each additional 10 pack-years smoked decreased with increasing genetic risk (HR = 1.56 at one SD below mean PRS, HR = 1.48 at mean PRS, and HR = 1.40 at one SD above mean PRS). Similarly, lung cancer risk per SD increase in the PRS was highest among those who had never smoked (HR = 1.55) and decreased with heavier smoking (HR = 1.32 at 30 pack-years). CONCLUSIONS: These results suggest the presence of a submultiplicative interaction between pack-years and genetics on lung cancer risk, consistent with recent findings. Both smoking and genetics were significantly associated with lung cancer risk. IMPACT: These results underscore the contributions of genetics and smoking on lung cancer risk and highlight the negative impact of continued smoking regardless of genetic risk.

Health Literacy-Informed Communication to Reduce Discharge Medication Errors in Hospitalized Children: A Randomized Clinical Trial.

Importance: Inadequate communication between caregivers and clinicians at hospital discharge contributes to medication dosing errors in children. Health literacy-informed communication strategies during medication counseling can reduce dosing errors but have not been tested in the pediatric hospital setting. Objective: To test a health literacy-informed communication intervention to decrease liquid medication dosing errors compared with standard counseling in hospitalized children. Design, Setting, and Participants: This parallel, randomized clinical trial was performed from June 22, 2021, to August 20, 2022, at a tertiary care, US children's hospital. English- and Spanish-speaking caregivers of hospitalized children 6 years or younger prescribed a new, scheduled liquid medication at discharge were included in the analysis. Interventions: Permuted block (n = 4) randomization (1:1) to a health literacy-informed discharge medication communication bundle (n = 99) compared with standard counseling (n = 99). A study team member delivered the intervention consisting of a written, pictogram-based medication instruction sheet, teach back (caregivers state information taught), and demonstration of dosing with show back (caregivers show how they would draw the liquid medication in the syringe). Main Outcome and Measures: Observed dosing errors, assessed using a caregiver-submitted photograph of their child's medication-filled syringe and expressed as the percentage difference from the prescribed dose. Secondary outcomes included caregiver-reported medication knowledge. Outcome measurements were blinded to participant group assignment. Results: Among 198 caregivers randomized (mean [SD] age, 31.4 [6.5] years; 186 women [93.9%]; 36 [18.2%] Hispanic or Latino and 158 [79.8%] White), the primary outcome was available for 151 (76.3%). The observed mean (SD) percentage dosing error was 1.0% (2.2 percentage points) among the intervention group and 3.3% (5.1 percentage points) among the standard counseling group (absolute difference, 2.3 [95% CI, 1.0-3.6] percentage points; P < .001). Twenty-four of 79 caregivers in the intervention group (30.4%) measured an incorrect dose compared with 39 of 72 (54.2%) in the standard counseling group (P = .003). The intervention enhanced caregiver-reported medication knowledge compared with the standard counseling group for medication dose (71 of 76 [93.4%] vs 55 of 69 [79.7%]; P = .03), duration of administration (65 of 76 [85.5%] vs 49 of 69 [71.0%]; P = .04), and correct reporting of 2 or more medication adverse effects (60 of 76 [78.9%] vs 13 of 69 [18.8%]; P < .001). There were no differences in knowledge of medication name, indication, frequency, or storage. Conclusions and Relevance: A health literacy-informed discharge medication communication bundle reduced home liquid medication administration errors and enhanced caregiver medication knowledge compared with standard counseling. Routine use of these standardized strategies can promote patient safety following hospital discharge. Trial Registration: ClinicalTrials.gov Identifier: NCT05143047.

Helicobacter pylori Burden in the United States According to Individual Demographics and Geography: A Nationwide Analysis of the Veterans Healthcare System.

BACKGROUND & AIMS: There are no contemporary large-scale studies evaluating the burden of Helicobacter pylori in the United States according to detailed demographics. The primary objective was to evaluate H pylori positivity in a large national healthcare system according to individual demographics and geography. METHODS: We conducted a nationwide retrospective analysis of adults in the Veterans Health Administration who completed H pylori testing between 1999 and 2018. The primary outcome was H pylori positivity overall, as well as according to zip code-level geography, race, ethnicity, age, sex, and time period. RESULTS: Among 913,328 individuals (mean, 58.1 years; 90.2% male) included between 1999 and 2018, H pylori was diagnosed in 25.8%. Positivity was highest in non-Hispanic black (median, 40.2%; 95% confidence interval [CI], 40.0%-40.5%) and Hispanic (36.7%; 95% CI, 36.4%-37.1%) individuals and lowest in non-Hispanic white individuals (20.1%; 95% CI, 20.0%-20.2%). Although H pylori positivity declined in all racial and ethnic groups over the timeframe, the disproportionate burden of H pylori in non-Hispanic black and Hispanic compared with non-Hispanic white individuals persisted. Approximately 4.7% of the variation in H pylori positivity was explained by demographics, with race and ethnicity accounting for the vast majority. CONCLUSIONS: The burden of H pylori is substantial in the United States among veterans. These data should (1) motivate research aimed at better understanding why marked demographic differences in H pylori burden persist so that mitigating interventions may be implemented and (2) guide resource allocation to optimize H pylori testing and eradication in high-risk groups.

Glycemic outcomes of a family-focused intervention for adults with type 2 diabetes: Main, mediated, and subgroup effects from the FAMS 2.0 RCT.

AIMS: Family/friend Activation to Motivate Self-care (FAMS) is a self-care support intervention delivered via mobile phones. We evaluated FAMS' effects on hemoglobin A1c (HbA1c) and intervention targets among adults with type 2 diabetes in a 15-month RCT. METHODS: Persons with diabetes (PWDs) were randomized to FAMS or control with their support person (family/friend, optional). FAMS included monthly phone coaching and text messages for PWDs, and text messages for support persons over a 9-month intervention period. RESULTS: PWDs (N = 329) were 52 % male, 39 % reported minoritized race or ethnicity, with mean HbA1c 8.6 ± 1.7 %. FAMS improved HbA1c among PWDs with a non-cohabitating support person (-0.64 %; 95 % CI [-1.22 %, -0.05 %]), but overall mean effects were not significant. FAMS improved intervention targets including self-efficacy, dietary behavior, and family/friend involvement during the intervention period; these improvements mediated post-intervention HbA1c improvements (total indirect effect -0.27 %; 95 % CI [-0.49 %, -0.09 %]) and sustained HbA1c improvements at 12 months (total indirect effect -0.19 %; 95 % CI [-0.40 %, -0.01 %]). CONCLUSIONS: Despite improvements in most intervention targets, HbA1c improved only among PWDs engaging non-cohabitating support persons suggesting future family interventions should emphasize inclusion of these relationships. Future work should also seek to identify intervention targets that mediate improvements in HbA1c.

Family Typology for Adults With Type 2 Diabetes: Longitudinal Stability and Validity for Diabetes Management and Well-being.

OBJECTIVE: We validated longitudinally a typology of diabetes-specific family functioning (named Collaborative and Helpful, Satisfied with Low Involvement, Want More Involvement, and Critically Involved) in adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted k-means cluster analyses with nine dimensions to determine if the typology replicated in a diverse sample and if type assignment was robust to variations in sampling and included dimensions. In a subsample with repeated assessments over 9 months, we examined the stability and validity of the typology. We also applied a multinomial logistic regression approach to make the typology usable at the individual level, like a diagnostic tool. RESULTS: Participants (N = 717) were 51% male, more than one-third reported minority race or ethnicity, mean age was 57 years, and mean hemoglobin A1c (HbA1c) was 7.9% (63 mmol/mol; 8.7% [72 mmol/mol] for the longitudinal subsample). The typology was replicated with respect to the number of types and dimension patterns. Type assignment was robust to sampling variations (97% consistent across simulations). Type had an average 52% stability over time within participants; instability was not explained by measurement error. Over 9 months, type was independently associated with HbA1c, diabetes self-efficacy, diabetes medication adherence, diabetes distress, and depressive symptoms (all P < 0.05). CONCLUSIONS: The typology of diabetes-specific family functioning was replicated, and longitudinal analyses suggest type is more of a dynamic state than a stable trait. However, type varies with diabetes self-management and well-being over time as a consistent independent indicator of outcomes. The typology is ready to be applied to further precision medicine approaches to behavioral and psychosocial diabetes research and care.

Well-being outcomes of a family-focused intervention for persons with type 2 diabetes and support persons: Main, mediated, and subgroup effects from the FAMS 2.0 RCT.

AIMS: Type 2 diabetes self-management occurs within social contexts. We sought to test the effects of Family/friend Activation to Motivate Self-care (FAMS), a self-care support intervention delivered via mobile phones, on psychosocial outcomes for persons with diabetes (PWDs) and their support persons. METHODS: PWDs had the option to enroll with a friend/family member as a support person in a 15-month RCT to evaluate FAMS versus enhanced usual care. FAMS included 9 months of monthly phone coaching and text message support for PWDs, and text message support for enrolled support persons. RESULTS: PWDs (N = 329) were 52% male and 39% reported minoritized race or ethnicity ; 50% enrolled with elevated diabetes distress. Support persons (N = 294) were 26% male and 33% reported minoritized race or ethnicity. FAMS improved PWDs' diabetes distress (d = -0.19) and global well-being (d = 0.21) during the intervention, with patterns of larger effects among minoritized groups. Post-intervention (9-month) and sustained (15-month) improvements were driven by changes in PWDs' self-efficacy, self-care behaviors, and autonomy support. Among support persons, FAMS improved helpful involvement without increasing burden or harmful involvement. CONCLUSIONS: FAMS improved PWDs' psychosocial well-being, with post-intervention and sustained improvements driven by improved self-efficacy, self-care, and autonomy support. Support persons increased helpful involvement without adverse effects.

Well-being outcomes of a family-focused intervention for persons with type 2 diabetes and support persons: Main, mediated, and subgroup effects from the FAMS 2.0 RCT.

Aims: Type 2 diabetes self-management occurs within social contexts. We sought to test the effects of Family/friends Activation to Motivate Self-care (FAMS), a self-care support intervention delivered via mobile phones, on psychosocial outcomes for persons with diabetes (PWDs) and their support persons. Methods: PWDs had the option to enroll with a friend/family member as a support person in a 15-month RCT to evaluate FAMS versus enhanced usual care. FAMS included 9-months of monthly phone coaching and text message support for PWDs, and text message support for enrolled support persons. Results: PWDs (N=329) were 52% male and 39% from minoritized racial or ethnic groups; 50% enrolled with elevated diabetes distress. Support persons (N=294) were 26% male and 33% minoritized racial or ethnic groups. FAMS improved PWDs' diabetes distress ( d =-0.19) and global well-being ( d =0.21) during the intervention, with patterns of larger effects among minoritized groups. Post-intervention and sustained (15-month) improvements were driven by changes in PWDs' self-efficacy, self-care behaviors, and autonomy support. Among support persons, FAMS improved helpful involvement without increasing burden or harmful involvement. Conclusions: FAMS improved PWDs' psychosocial well-being, with post-intervention and sustained improvements driven by improved self-efficacy, self-care, and autonomy support. Support persons increased helpful involvement without adverse effects.

Glycemic outcomes of a family-focused intervention for adults with type 2 diabetes: Main, mediated, and subgroup effects from the FAMS 2.0 RCT.

Aims: Family/friends Activation to Motivate Self-care (FAMS) is a self-care support intervention delivered via mobile phones. We evaluated FAMS effects on hemoglobin A1c (HbA1c) and intervention targets among adults with type 2 diabetes in a 15-month RCT. Methods: Persons with diabetes (PWDs) and their support persons (family/friend, optional) were randomized to FAMS or control. FAMS included monthly phone coaching and text messages for PWDs, and text messages for support persons over a 9-month intervention period. Results: PWDs (N=329) were 52% male, 39% from minoritized racial or ethnic groups, with mean HbA1c 8.6±1.7%. FAMS improved HbA1c among PWDs with a non-cohabitating support person (-0.64%; 95% CI [-1.22%, -0.05%]), but overall effects were not significant. FAMS improved intervention targets including self-efficacy, dietary behavior, and family/friend involvement during the intervention period; these improvements mediated post-intervention HbA1c improvements (total indirect effect -0.27%; 95% CI [-0.49%, -0.09%]) and sustained HbA1c improvements at 12 months (total indirect effect -0.19%; 95% CI [-0.40%, -0.01%]). Conclusions: Despite improvements in most intervention targets, HbA1c improved only among PWDs engaging non-cohabitating support persons suggesting future family interventions should emphasize inclusion of these relationships. Future work should also seek to identify intervention targets that mediate improvements in HbA1c.

Prerandomization withdrawals from a Type 2 diabetes self-care support intervention trial are associated with lack of available support person coparticipant.

OBJECTIVES: Dyadic interventions, involving two persons with a preexisting close relationship, offer the opportunity to activate support persons (SPs) to improve health for adults with chronic conditions. Requiring SP coparticipation can challenge recruitment and bias samples; however, the associations between voluntary SP coparticipation and recruitment outcomes across patient characteristics are unknown. METHODS: The Family/Friend Activation to Motivate Self-care 2.0 randomized controlled trial (RCT) enrolled adults with Type 2 diabetes (T2D) from an academic health system. Participants were asked-but not required-to invite an SP to coenroll. Using data from the electronic health record we sought to describe RCT enrollment in the setting of voluntary SP coparticipation. RESULTS: In a diverse sample of adults with (T2D) (48% female, 44% minoritized race/ethnicity), most participants (91%) invited SPs and (89%) enrolled with SPs. However, prerandomization withdrawal was significantly higher among participants who did not have consenting SPs than those who did. Females were less likely to invite SPs than males and more Black PWD were prerandomization withdrawals than randomized. DISCUSSION: Voluntary SP coenrollment may benefit recruitment for dyadic sampling; however, more research is needed to understand if these methods systematically bias sampling and to prevent these unintended biases.

Bile Acid Sequestrant Use and Gastric Cancer: A National Retrospective Cohort Analysis.

INTRODUCTION: Bile acids have been implicated in gastric carcinogenesis. We hypothesized that bile acid sequestrant medication (BAM) use is associated with a lower gastric cancer (GC) incidence. METHODS: We assembled a cohort of veterans receiving longitudinal care within the Veterans Health Administration between 2000 and 2020 who completed testing for Helicobacterpylori . The index date was the date of completed H. pylori testing. The primary exposure was the number of filled BAM prescription(s) in the 5 years before the index date. The primary outcome was incident GC, stratified by anatomic subsite. Follow-up began at the index date and ended at the earliest of GC, death, after 2 years of follow-up, or the study end (May 31, 2020). We used Kaplan-Meier curves to visualize differences in GC incidence by exposure group and multivariable Cox proportional hazards models to estimate the association between BAM exposure and anatomic site-specific GC. RESULTS: Among 417,239 individuals (89% male, mean age 54 years, 63% non-Hispanic White), 4,916 (1.2%) filled at least one BAM prescription, 2,623 of whom filled ≥4. Compared with unexposed individuals, those with ≥4 BAM fills before entry had a lower incidence (adjusted hazard ratio 0.71; 95% confidence interval, 0.37-1.36) of GC, but confidence intervals were wide. Results were consistent irrespective of GC anatomic site. DISCUSSION: BAMs may have a protective effect against both cardia and noncardia GC. Further research and external validation are needed to confirm these findings.

Rematching on-the-fly: Sequential matched randomization and a case for covariate-adjusted randomization.

Covariate-adjusted randomization (CAR) can reduce the risk of covariate imbalance and, when accounted for in analysis, increase the power of a trial. Despite CAR advances, stratified randomization remains the most common CAR method. Matched randomization (MR) randomizes treatment assignment within optimally identified matched pairs based on covariates and a distance matrix. When participants enroll sequentially, sequentially matched randomization (SMR) randomizes within matches found "on-the-fly" to meet a pre-specified matching threshold. However, pre-specifying the ideal threshold can be challenging and SMR yields less-optimal matches than MR. We extend SMR to allow multiple participants to be randomized simultaneously, to use a dynamic threshold, and to allow matches to break and rematch if a better match later enrolls (sequential rematched randomization; SRR). In simplified settings and a real-world application, we assess whether these extensions improve covariate balance, estimator/study efficiency, and optimality of matches. We investigate whether adjusting for more covariates can be detrimental upon covariate balance and efficiency as is the case of traditional stratified randomization. As secondary objectives, we use the case study to assess how SMR schemes compare side-by-side with common and related CAR schemes and whether adjusting for covariates in the design can be as powerful as adjusting for covariates in a parametric model. We find each SMR extension, individually and collectively, to improve covariate balance, estimator efficiency, study power, and quality of matches. We provide a case-study where CAR schemes with randomization-based inference can be as and more powerful than non-CAR schemes with parametric adjustment for covariates.

Validation of an algorithm to identify fractures among patients within the Veterans Health Administration.

OBJECTIVE: To validate an algorithm that identifies fractures using billing codes from the International Classification of Diseases Ninth Revision (ICD-9) and Tenth Revision (ICD-10) for inpatient, outpatient, and emergency department visits in a population of patients. METHODS: We identified and reviewed a random sample of 543 encounters for adults receiving care within a single Veterans Health Administration healthcare system and had a first fracture episode between 2010 and 2019. To determine if an encounter represented a true incident fracture, we performed chart abstraction and assessed the type of fracture and mechanism. We calculated the positive predictive value (PPV) for the overall algorithm and each component diagnosis code along with 95% confidence intervals. Inverse probabilities of selection sampling weights were used to reflect the underlying study population. RESULTS: The algorithm had an initial PPV of 73.5% (confidence interval [CI] 69.5, 77.1), with low performance when weighted to reflect the full population (PPV 66.3% [CI 58.8, 73.1]). The modified algorithm was restricted to diagnosis codes with PPVs > 50% and outpatient codes were restricted to the first outpatient position, with the exception of one high performing code. The resulting unweighted PPV improved to 90.1% (CI 86.2, 93.0) and weighted PPV of 91.3% (CI 86.8, 94.4). A confirmation sample demonstrated verified performance with PPV of 87.3% (76.0, 93.7). PPVs by location of care (inpatient, emergency department and outpatient) remained greater than 85% in the modified algorithm. CONCLUSIONS: The modified algorithm, which included primary billing codes for inpatient, outpatient, and emergency department visits, demonstrated excellent PPV for identification of fractures among a cohort of patients within the Veterans Health Administration system.

Primary Occurrence of Cardiovascular Events After Adding Sodium-Glucose Cotransporter-2 Inhibitors or Glucagon-like Peptide-1 Receptor Agonists Compared With Dipeptidyl Peptidase-4 Inhibitors: A Cohort Study in Veterans With Diabetes.

BACKGROUND: The effectiveness of glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) in preventing major adverse cardiac events (MACE) is uncertain for those without preexisting cardiovascular disease. OBJECTIVE: To test the hypothesis that MACE incidence was lower with the addition of GLP1RA or SGLT2i compared with dipeptidyl peptidase-4 inhibitors (DPP4i) for primary cardiovascular prevention. DESIGN: Retrospective cohort study of U.S. veterans from 2001 to 2019. SETTING: Veterans aged 18 years or older receiving care from the Veterans Health Administration, with data linkage to Medicare, Medicaid, and the National Death Index. PATIENTS: Veterans adding GLP1RA, SGLT2i, or DPP4i onto metformin, sulfonylurea, or insulin treatment alone or in combination. Episodes were stratified by history of cardiovascular disease. MEASUREMENTS: Study outcomes were MACE (acute myocardial infarction, stroke, or cardiovascular death) and heart failure (HF) hospitalization. Cox models compared the outcome between medication groups using pairwise comparisons in a weighted cohort adjusted for covariates. RESULTS: The cohort included 28 759 GLP1RA versus 28 628 DPP4i weighted pairs and 21 200 SGLT2i versus 21 170 DPP4i weighted pairs. Median age was 67 years, and diabetes duration was 8.5 years. Glucagon-like peptide-1 receptor agonists were associated with lower MACE and HF versus DPP4i (adjusted hazard ratio [aHR], 0.82 [95% CI, 0.72 to 0.94]), yielding an adjusted risk difference (aRD) of 3.2 events (CI, 1.1 to 5.0) per 1000 person-years. Sodium-glucose cotransporter-2 inhibitors were not associated with MACE and HF (aHR, 0.91 [CI, 0.78 to 1.08]; aRD, 1.28 [-1.12 to 3.32]) compared with DPP4i. LIMITATION: Residual confounding; use of DPP4i, GLP1RA, and SGLT2i as first-line therapies were not examined. CONCLUSION: The addition of GLP1RA was associated with primary reductions of MACE and HF hospitalization compared with DPP4i use; SGLT2i addition was not associated with primary MACE prevention. PRIMARY FUNDING SOURCE: VA Clinical Science Research and Development and supported in part by the Centers for Diabetes Translation Research.

Family involvement and diabetes distress across dyads for adults with type 2 diabetes.

OBJECTIVE: Family/friend involvement and diabetes distress are associated with outcomes for persons with type 2 diabetes (PWDs), but little is known about how they relate to each other. We aim to (1) describe associations between PWD and support person (SP) distress; (2) describe associations between involvement and diabetes distress for PWDs, for SPs, and across the dyad; and (3) explore whether associations differ by PWD-SP cohabitation. METHODS: PWDs and SPs co-enrolled in a study evaluating the effects of a self-care support intervention and completed self-report measures at baseline. RESULTS: PWDs and SPs (N = 297 dyads) were, on average, in their mid-50s and around one-third identified as racial or ethnic minorities. The association between PWD and SP diabetes distress was small (Spearman's ρ = 0.25, p < 0.01). For PWDs, experienced harmful involvement from family/friends was associated with more diabetes distress (standardized ß = 0.23, p < 0.001) independent of helpful involvement in adjusted models. Separately, SPs' self-reported harmful involvement was associated with their own diabetes distress (standardized ß = 0.35, p < 0.001) and with PWDs' diabetes distress (standardized ß = 0.25, p = 0.002), independent of SPs' self-reported helpful involvement. CONCLUSION AND PRACTICE IMPLICATIONS: Findings suggest dyadic interventions may need to address both SP harmful involvement and SP diabetes distress, in addition to PWD distress.

Geographic Variation in Access to Cardiac Rehabilitation.

BACKGROUND: There is marked geographic variation in cardiac rehabilitation (CR) initiation, ranging from 10% to 40% of eligible patients at the state level. The potential causes of this variation, such as patient access to CR centers, are not well studied. OBJECTIVES: The authors sought to determine how access to CR centers affects CR initiation in Medicare beneficiaries. METHODS: The authors used Medicare files to identify CR-eligible Medicare beneficiaries and calculate CR initiation rates at the hospital referral region (HRR) level. We used linear regression to evaluate the percent variation in CR initiation accounted for by CR access across HRRs. We then employed geospatial hotspot analysis to identify CR deserts, or counties in which patient load per CR center is disproportionately high. RESULTS: A total of 1,133,657 Medicare beneficiaries were eligible for CR from 2014 to 2017, of whom 263,310 (23%) initiated CR. The West North Central Census Division had the highest adjusted CR initiation rate (35.4%) and the highest density of CR programs (6.58 per 1,000 CR-eligible Medicare beneficiaries). Density of CR programs accounted for 21.2% of geographic variation in CR initiation at the HRR level. A total of 40 largely urban counties comprising 14% of the United States population age ≥65 years had disproportionately low CR access and were identified as CR deserts. CONCLUSIONS: A substantial proportion of geographic variation in CR initiation was related to access to CR programs, with a significant amount of the U.S. population living in CR deserts. These data invite further study on interventions to increase CR access.

Comparative effectiveness of metformin versus sulfonylureas on kidney function decline or death among patients with reduced kidney function: a retrospective cohort study.

BACKGROUND: Diabetes often causes kidney disease. In this study, we sought to evaluate if metformin use was associated with death or kidney events in patients with diabetes and concurrent reduced kidney function. METHODS: We used data from the Veterans Health Administration, Medicare and National Death Index databases to assemble a national retrospective cohort of veterans who were using metformin or sulfonylureas from 2001 through 2016 and who began follow-up at an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2. The primary composite outcome was a kidney event (i.e., 40% decline in eGFR or end-stage renal disease) or death. The secondary outcome was a kidney event (eGFR decline or end-stage renal disease). We weighted the cohort using propensity scores and used Cox proportional models to estimate the cause-specific hazard of outcomes and of treatment nonpersistence as a competing risk. We stratified follow-up into 2 periods, namely the first 360 days from the start of follow-up, and 361 days and beyond. RESULTS: In the first 360 days, the propensity score-weighted cohort included 24 883 patients who used metformin and 24 998 who used sulfonylureas. There were 33.5 (95% confidence interval [CI] 30.9-36.3) and 43.0 (95% CI 40.1-46.0) deaths or kidney events per 1000 person-years for patients who used metformin or sulfonylureas, respectively (hazard ratio [HR] 0.78, 95% CI 0.71-0.85). For the secondary outcome of kidney events, the HR was 0.94 (95% CI 0.67-1.33). In the second period from 361 days onward, the primary outcome event rate was 26.5 (95% CI 24.7-28.5) per 1000 person-years for those who used metformin, compared with 36.3 (95% CI 34.2-38.6) per 1000 person-years for those who used sulfonylureas (HR 0.73, 95% CI 0.67-0.79). Results were consistent for kidney events alone (HR 0.73, 95% CI 0.59-0.91). INTERPRETATION: Metformin use for 361 days or longer after reaching an eGFR of less than 60 mL/min/1.73 m2 was associated with decreased likelihood of kidney events or death in patients with diabetes, compared with use of sulfonylureas. Metformin provided end-organ protection, in addition to glucose control.