The Association of Odor Identification With Nutritional Status and Systemic Inflammation in Patients With Advanced Chronic Kidney Disease.

OBJECTIVES: Anorexia is common in patients with chronic kidney disease (CKD) and could lead to protein-energy wasting (PEW). An altered sense of smell, a reflection of olfactory dysfunction, is a potential mechanism that exacerbates the impact of anorexia on PEW. In this study, we examined the extent of the altered sense of smell and its association with PEW in patients with moderate-to-advanced CKD. METHODS: We studied 139 individuals (34 healthy subjects- controls, 50 patients with stage 3-4 CKD, and 55 patients on maintenance hemodialysis (MHD)) using the odor identification test (Sniffin' Sticks odor screening test containing 12 different smells). The odor identification test was scored as either correct or incorrect, and each participant's total odor score was calculated. Malnutrition inflammation score (MIS) was used to assess PEW. RESULTS: Patients with CKD had higher C-reactive protein and lower serum albumin concentrations compared to healthy individuals. Total odor scores were different between groups, with controls having the highest scores and MHD patients having the lowest scores. A similar difference was observed in MIS, and MHD patients displayed the worst nutritional score (P ≤ .001). The number of participants with severe olfactory dysfunction (≤6 correct answers) was significantly higher in the CKD and MHD groups compared to the controls (P ≤ .01). There was an inverse trend between the total odor score and the MIS score for the study population. However, this relationship was not statistically significant (r = -0.124, P = .21). CONCLUSION: This cross-sectional study suggests that olfactory dysfunction, as assessed by the odor identification test, is altered in patients with advanced CKD, most notably in ones on MHD. Although the diminished sense of smell was observed alongside development of PEW, we explicitly noted that there is no statistically significant correlation.

Ascertainment of Helicobacter pylori Infection and Eradication Treatment Using a Nationwide Electronic Health Record Database.

Background and Aims: There are limited contemporary population-based data on Helicobacter pylori epidemiology and outcomes in the United States. Our primary aim was to create a validated cohort of veterans with H pylori testing or treatment using Veterans Health Administration data. Methods: Using Veterans Health Administration structured and unstructured data, we developed and validated 4 algorithms for H pylori infection (3 algorithms) and treatment status (1 algorithm). During the development phase, we iteratively modified each algorithm based on a manual review of random sets of electronic health records (reference standard). The a priori validation goal was to achieve a one-sided 95% confidence lower bound (LB) for positive predictive value (PPV) and/or negative predictive value (NPV) >90%. We applied the Bonferroni correction when both PPV and NPV were relevant. Results: For H pylori infection, we achieved 99.0% PPV (LB = 94.6%) and 100% NPV (LB = 96.4%) for discriminating H pylori positive vs negative status using structured (ie, laboratory tests) and 95% PPV (LB = 90.3%) and 97.9% NPV (LB = 93.9%) using unstructured (ie, histopathology reports) data. Diagnostic codes achieved 98% PPV (LB = 93.0%) for H pylori diagnosis. The treatment algorithm was composed of multiple antimicrobial combinations and overall achieved ≥98% PPV (LB = 93.0%) for H pylori treatment, except for amoxicillin/levofloxacin (PPV<60%). Application of these algorithms yielded nearly 1.2 million veterans with H pylori testing and/or treatment between 1999 and 2018. Conclusion: We assembled a validated national cohort of veterans who were tested or treated for H pylori infection. This cohort can be used for evaluating H pylori epidemiology and treatment patterns, as well as complications of chronic infection.

Ultrafiltration Patterns during Automated Peritoneal Dialysis: Findings and Insights to Peritoneal Physiology.

BACKGROUND: With the growing use of automated peritoneal dialysis (APD), it is important to improve our knowledge of the clinical patterns and physiology of APD treatment sessions. The ultrafiltration (UF) achieved during each cycle of an APD treatment is assumed to be relatively linear if the delivered prescription is the same. We set out to determine if that is indeed the case. METHODS: Single-center, cross-sectional study of prevalent PD patients. All adult APD patients (> 18 years of age), who had been on PD for >3 months, and >3 months on APD were included. Continuous ambulatory PD patients or those with peritonitis within 3 months of the consent date were excluded. Individual treatment data from 7 consecutive APD treatment sessions with consistent dialysate composition for each cycler exchange were collected for each subject. RESULTS: Thirty-nine subjects met the inclusion criteria and were enrolled. The probability of yielding a positive UF was 48.9% for cycle 1, rising to 90.5% by cycle 6. Adjusting for average dextrose concentration, dwell time, fill volume, solute transfer rate, and number of cycles, we observed that cycles 2 through 6 achieved progressively higher UF volumes than cycle 1 (p < 0.001). The first and last cycles demonstrated significantly different cycle UF volumes compared to a middle cycle (-230 ml and 277 ml, respectively, p < 0.001). CONCLUSIONS: We observed a consistent increase in UF volumes achieved per cycle over the course of an APD treatment session with numerous clinical and physiologic implications. This provides the foundation for future studies investigating peritoneal inter-cycle variations and membrane physiology.

Genome-wide association study of hospitalized patients and acute kidney injury.

Acute kidney injury (AKI) is a common and devastating complication of hospitalization. Here, we identified genetic loci associated with AKI in patients hospitalized between 2002-2019 in the Million Veteran Program and data from Vanderbilt University Medical Center's BioVU. AKI was defined as meeting a modified KDIGO Stage 1 or more for two or more consecutive days or kidney replacement therapy. Control individuals were required to have one or more qualifying hospitalizations without AKI and no evidence of AKI during any other observed hospitalizations. Genome-wide association studies (GWAS), stratified by race, adjusting for sex, age, baseline estimated glomerular filtration rate (eGFR), and the top ten principal components of ancestry were conducted. Results were meta-analyzed using fixed effects models. In total, there were 54,488 patients with AKI and 138,051 non-AKI individuals included in the study. Two novel loci reached genome-wide significance in the meta-analysis: rs11642015 near the FTO locus on chromosome 16 (obesity traits) (odds ratio 1.07 (95% confidence interval, 1.05-1.09)) and rs4859682 near the SHROOM3 locus on chromosome 4 (glomerular filtration barrier integrity) (odds ratio 0.95 (95% confidence interval, 0.93-0.96)). These loci colocalized with previous studies of kidney function, and genetic correlation indicated significant shared genetic architecture between AKI and eGFR. Notably, the association at the FTO locus was attenuated after adjustment for BMI and diabetes, suggesting that this association may be partially driven by obesity. Both FTO and the SHROOM3 loci showed nominal evidence of replication from diagnostic-code-based summary statistics from UK Biobank, FinnGen, and Biobank Japan. Thus, our large GWA meta-analysis found two loci significantly associated with AKI suggesting genetics may explain some risk for AKI.

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.

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.

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.

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.

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.

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.