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Aim: To evaluate whether recent low adherence to metformin monotherapy is associated with hypoglycaemia after addition of a sulfonylurea. Methods: We assembled a retrospective cohort of veterans who filled a new prescription for metformin between 2001 and 2011 and intensified treatment with a sulfonylurea after ≥1 year of metformin use. We calculated metformin adherence from pharmacy data using the proportion of days covered in the 180‐day period before intensification. The primary outcome was hypoglycaemia, defined as a hospitalization or emergency department visit for hypoglycaemia or an outpatient blood glucose measurement <3.3 mmol/l in the year following intensification. Cox proportional hazards models were used to compare the risk of hypoglycaemia between participants with low (<80%) and high (≥80%) adherence. Adherence was also modelled as a continuous variable using restricted cubic splines. Results: Of 187 267 participants who initiated metformin monotherapy, 49 424 added a sulfonylurea after ≥1 year. The median (interquartile range) rate of treatment adherence was 87 (50–100)% and 43% had adherence <80%. Hypoglycaemia rates per 1000 person‐years were 23.1 (95% CI 21.1–25.4) and 24.5 (95% CI 22.7–26.4) in participants with low and high adherence, respectively (adjusted hazard ratio 0.95, 95% CI 0.84–1.08). The risk of hypoglycaemia was similar across all levels of adherence when adherence was modelled as a continuous variable. Conclusions: We found no evidence that past low adherence to metformin monotherapy was associated with hypoglycaemia after intensification with a sulfonylurea. What's new?: Providers often intensify anti‐hyperglycaemic treatment for people with Type 2 diabetes mellitus based on laboratory measurements without accurate assessment of adherence, potentially exposing those with low adherence to a more intensive regimen than necessary.This retrospective cohort study, which included incident users of metformin intensifying treatment, found that recent low adherence to metformin monotherapy was not associated with hypoglycaemia in the year following intensification with a sulfonylurea.While it is important for providers to evaluate medication adherence, this study does not suggest that intensifying treatment in the presence of recent non‐adherence is associated with a higher risk of hypoglycaemia. [ABSTRACT FROM AUTHOR]

Importance: The COVID-19 pandemic stressed the healthcare field, resulting in a worker exodus at the onset and throughout the pandemic and straining healthcare systems. Female healthcare workers face unique challenges that may impact job satisfaction and retention. It is important to understand factors related to healthcare workers' intent to leave their current field., Objective: To test the hypothesis that female healthcare workers were more likely than male counterparts to report intention to leave., Design: Observational study of healthcare workers enrolled in the Healthcare Worker Exposure Response and Outcomes (HERO) registry. After baseline enrollment, two HERO 'hot topic' survey waves, in May 2021 and December 2021, ascertained intent to leave. Unique participants were included if they responded to at least one of these survey waves., Setting: HERO registry, a large national registry that captures healthcare worker and community member experiences during the COVID-19 pandemic., Participants: Registry participants self-enrolled online and represent a convenience sample predominantly composed of adult healthcare workers., Exposure(s): Self-reported gender (male, female)., Main Outcome: Primary outcome was intention to leave (ITL), defined as having already left, actively making plans, or considering leaving healthcare or changing current healthcare field but with no active plans. Multivariable logistic regression models were performed to examine the odds of intention to leave with adjustment for key covariates., Results: Among 4165 responses to either May or December surveys, female gender was associated with increased odds of ITL (42.2% males versus 51.4% females reported intent to leave; aOR 1.36 [1.13, 1.63]). Nurses had 74% higher odds of ITL compared to most other health professionals. Among those who expressed ITL, three quarters reported job-related burnout as a contributor, and one third reported experience of moral injury., Conclusions and Relevance: Female healthcare workers had higher odds of intent to leave their healthcare field than males. Additional research is needed to examine the role of family-related stressors., Trial Registration: ClinicalTrials.gov identifier NCT04342806., Competing Interests: The authors declare competing financial interests as follows. Dr. Linzer is supported through his employer Hennepin Healthcare for work by large healthcare organizations to reduce burnout (ABIM, ACP, AMA, IHI, Optum Office for Provider Advancement, Essentia Health Systems, Gillette Children’s Hospital and California AHEC). He is supported for other scholarly work by NIH and AHRQ, and consults for Harvard University on a grant to assess relationships between work conditions and diagnostic accuracy (consulting funds donated to Hennepin Healthcare). This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Apple et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Social determinants of health (SDH) contribute to nearly 50% of health outcomes; however, SDH data collection is inconsistent in clinical practice. This study used mixed methods to evaluate health care professionals' perceptions of universal SDH screening at an academic medical center by surveying physicians, advanced practice providers, nurses, social workers, case managers, pharmacists, and administrators. An electronic survey assessed SDH screening practices, prioritization of SDH domains, disciplines to perform screening, and attitudes and barriers to universal screening. Likert-scale responses were dichotomized and compared disciplines with proportions tests. Qualitative interviews identified themes and elaborated survey findings. Participant discipline was the primary predictor variable. Of 193 survey participants (62.5% response rate), most were physicians (31%) or social workers (22%). Participants overwhelmingly reported using SDH information in patient care (93%), and social workers as the most appropriate role for screening (95%). Most respondents (75%) believed health literacy is important, but 40% reported routine assessment. Housing status (73% vs. 53%) and financial strain (62% vs. 48%) followed similar patterns. SDH screening barriers included lacking resources to address identified needs (51%), time to ask (45%), support staff to ask (33%), and training in responding to identified needs (28%). Social workers cited barriers less often than non-social workers ( P  < 0.001). Qualitative interviews (n = 16) supported survey findings and described barriers including lack of time, resources, standardized approaches, and professional burnout. Health care professionals support universal SDH screening while highlighting the need to address implementation barriers. Strategies should leverage social work expertise and optimize SDH data accessibility for all providers.

Background & Aims: Helicobacter pylori infects approximately 50% of individuals worldwide. Successful H pylori eradication is associated with reduced risk of gastric cancer and peptic ulcer disease, among other conditions. We hypothesized that host genetic determinants, especially those affecting gastric pH, might contribute to eradication therapy failure, particularly when treatment adherence and antibiotic susceptibility are confirmed. We aimed to conduct a meta-analysis of host genetic variants associated with H pylori eradication failure., Methods: We searched the literature for studies comparing posttreatment H pylori eradication failure vs success (outcome) according to host genetic polymorphisms (exposure). Reference groups were defined according to genotypes (or corresponding phenotypes) hypothesized to be associated with successful eradication. We pooled estimates using a random-effects model and performed comprehensive sensitivity analyses., Results: We analyzed 57 studies from 11 countries; the vast majority analyzed CYP2C19 polymorphisms. Among individuals prescribed eradication regimens with proton pump inhibitors predominantly CYP2C19 metabolized, enhanced vs poor metabolizer phenotypes were associated with a 2.52-fold significantly higher likelihood of eradication failure and 4.44-fold significantly higher likelihood when treatment adherence and H pylori clarithromycin susceptibility (if relevant) were confirmed. There was no association between CYP2C19 variants and eradication failure if proton pump inhibitors less metabolized by or that bypass CYP2C19 metabolism were used. IL1B polymorphisms that are vs are not associated with less gastric acid suppression were associated with 1.72-fold significantly higher likelihood of eradication failure. There was no association between MDR1 polymorphisms and H pylori eradication failure. The certainty of evidence was moderate., Conclusion: Based on meta-analysis, we identified host genetic polymorphisms significantly associated with H pylori eradication failure; host genetics might underlie eradication failure among treatment-adherent individuals with confirmed H pylori antibiotic susceptibility., (Published by Elsevier Inc.)

Background: Antibiotics are not recommended for treatment of acute uncomplicated bronchitis (AUB), but are often prescribed (85% of AUB visits within the Veterans Affairs nationally). This quality improvement project aimed to decrease antibiotic prescribing for AUB in community-based outpatient centres from 65% to <32% by April 2020., Methods: From January to December 2018, community-based outpatient clinics' 6 months' average of prescribed antibiotics for AUB and upper respiratory infections was 63% (667 of 1054) and 64.6% (314 of 486) when reviewing the last 6 months. Seven plan-do-study-act (PDSA) cycles were implemented by an interprofessional antimicrobial stewardship team between January 2019 and March 2020. Balancing measures were a return patient phone call or visit within 4 weeks for the same complaint. Χ 2 tests and statistical process control charts using Western Electric rules were used to analyse intervention data., Results: The AUB antibiotic prescribing rate decreased from 64.6% (314 of 486) in the 6 months prior to the intervention to 36.8% (154 of 418) in the final 6 months of the intervention. No change was seen in balancing measures. The largest reduction in antibiotic prescribing was seen after implementation of PDSA 6 in which 14 high prescribers were identified and targeted for individualised reviews of encounters of patients with AUB with an antimicrobial steward., Conclusions: Operational implementation of successful stewardship interventions is challenging and differs from the traditional implementation study environment. As a nascent outpatient stewardship programme with limited resources and no additional intervention funding, we successfully reduced antibiotic prescribing from 64.6% to 36.8%, a reduction of 43% from baseline. The most success was seen with targeted education of high prescribers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: ST-segment elevation myocardial infarction (STEMI) predominantly affects older adults. Lower incidence among younger patients may challenge diagnosis., Objectives: We hypothesize that among patients ≤ 50 years old, emergent percutaneous coronary intervention (PCI) for STEMI is delayed when compared with patients aged > 50 years., Methods: This 3-year, 10-center retrospective cohort study included emergency department (ED) STEMI patients ≥ 18 years of age treated with emergent PCI. We excluded patients with an electrocardiogram (ECG) completed prior to ED arrival or a nondiagnostic initial ECG. Our primary outcome was door-to-balloon (D2B) time. We compared characteristics and outcomes among younger vs. older STEMI patients, and among age subgroups., Results: There were 576 ED STEMI PCI patients, of whom 100 were ≤ 50 years old and 476 were > 50 years old. Median age was 44 years in the younger cohort (interquartile range [IQR] 41-47) vs. 62 years (IQR 57-70) among older patients. Median D2B time for the younger cohort was 76.5 min (IQR 67.5-102.5) vs. 81.0 min (IQR 65.0-105.5) in the older cohort (p = 0.91). This outcome did not change when ages 40 or 45 years were used to demarcate younger vs. older. The younger cohort had a higher prevalence of nonwhite races (38% vs. 21%; p < 0.001) and those currently smoking (36% vs. 23%; p = 0.005). The very young (≤30 years; 6/576) and very old (>80 years; 45/576) had 5.51 and 2.2 greater odds of delays., Conclusion: We found no statistically significant difference in D2B times between patients ≤ 50 years old and those > 50 years old. Nonwhite patients and those who smoke were disproportionately represented within the younger population. The very young and very old had higher odds of D2B times > 90 min., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background/objectives: Chronic kidney disease (CKD) is associated with frailty. Fibroblast growth factor 23 (FGF23) is elevated in CKD and associated with frailty among non-CKD older adults and individuals with human immunodeficiency virus. Whether FGF23 is associated with frailty and falls in CKD is unknown., Design: Cross-sectional and longitudinal observational study., Setting: Systolic Blood Pressure Intervention Trial (SPRINT), a randomized trial evaluating standard (systolic blood pressure [SBP] <140 mm Hg) versus intensive (SBP <120 mm Hg) blood pressure lowering on cardiovascular and cognitive outcomes among older adults without diabetes mellitus., Participants: A total of 2,376 participants with CKD (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m 2 )., Measurements: The exposure variable was intact FGF23. We used multinomial logistic regression to determine the cross-sectional association of intact FGF23 with frailty and Cox proportional hazards analysis to determine the longitudinal association with incident falls. Models were adjusted for demographics, comorbidities, randomization group, antihypertensives, eGFR, mineral metabolism markers, and frailty., Results: After adjustment, the odds ratio for prevalent frailty versus non-frailty per twofold higher FGF23 was 1.34 (95% confidence interval [CI] = 1.01-1.77). FGF23 levels in the highest quartile versus the lowest quartile demonstrated more than a twofold increased fall risk (hazard ratio [HR] = 2.32; 95% CI = 1.26-4.26), and the HR per twofold higher FGF23 was 1.99 (95% CI = 1.48-2.68)., Conclusion: Among SPRINT participants with CKD, FGF23 was associated with prevalent frailty and falls., (© 2020 The American Geriatrics Society.)

Background: Risk reduction through dietary modifications is an adjunct strategy for prevention of oesophageal cancer, a leading cause of cancer-related mortality and morbidity worldwide. We aimed to estimate the association between calcium and magnesium intakes and incident oesophageal cancer (OC)., Methods: We conducted a retrospective analysis of the NIH-AARP Diet and Health Study prospective cohort. We used multivariable Cox proportional hazard modeling to estimate the association between total intakes and incident OC overall and by histology (oesophageal squamous cell carcinoma (OSCC) and adenocarcinoma (OAC)). Sensitivity and stratified analyses were performed., Results: Among 536,359 included respondents, 1414 incident OCs occurred over 6.5 million person-years follow-up time. Increasing dietary calcium intake was associated with an adjusted 32-41% lower risk of OSCC compared to the lowest quartile (p-trend 0.01). There was a positive association between increasing magnesium intake and OAC risk, but only among participants with low calcium:magnesium intake ratios (p-trend 0.04). There was a significant interaction with smoking status., Conclusions: Based on a retrospective analysis of the NIH-AARP Diet and Health Study prospective cohort, dietary intakes of calcium and magnesium were significantly associated with risk of OSCC and, among certain participants, OAC, respectively. If validated, these findings could inform dietary modifications among at-risk individuals. Mechanistic investigations would provide additional insight.

Gastric cancer remains a leading cause of cancer-related mortality. Identifying dietary and other modifiable disease determinants has important implications for risk attenuation in susceptible individuals. Our primary aim was to estimate the association between dietary and supplemental intakes of calcium and magnesium and the risk of incident gastric cancer. We conducted a prospective cohort analysis of the National Institutes of Health-American Association of Retired Persons Diet and Health Study. We used Cox proportional hazard modeling to estimate the association between calcium and magnesium intakes with risk of incident gastric adenocarcinoma (GA) overall and by anatomic location, noncardia GA (NCGA) and cardia GA (CGA). A total of 536,403 respondents (59% males, 41% females) were included for analysis, among whom 1,518 incident GAs (797 NCGA and 721 CGA) occurred. Increasing calcium intake was associated with lower risk of GA overall (p-trend = 0.05), driven primarily by the association with NCGA, where the above median calcium intakes were associated with a 23% reduction in risk compared to the lowest quartile (p-trend = 0.05). This magnitude of NCGA risk reduction was greater among nonwhite ethnic group and Hispanics (hazard ratio [HR] 0.51, 95% confidence interval [CI]: 0.24-1.07, p-trend = 0.04), current/former smokers (HR 0.58, 95% CI: 0.41-0.81), obese individuals (HR 0.54, 95% CI: 0.31-0.96) and those with high NCGA risk scores (HR 0.50, 95% CI: 0.31-0.80). Among men only, increasing magnesium intake was associated with 22-27% reduced risk of NCGA (p-trend = 0.05), while for the cohort, dietary magnesium intake in the highest vs. lowest quartile was associated with a 34% reduced risk of NCGA (HR 0.66, 95% CI: 0.48-0.90). These findings have important implications for risk factor modification. Future investigations are needed not only to confirm our results, but to define mechanisms underlying these associations., (© 2019 UICC.)

In a prospective cohort study of Veterans and community health nurses, we enrolled hospitalized older Veterans referred to home care for skilled nursing and/or physical or occupational therapy for posthospitalization care. We assessed preadmission activities of daily living and instrumental activities of daily living, health literacy, numeracy, and cognition. Postdischarge phone calls identified medication errors and medication reconciliation efforts by home healthcare clinicians. Veterans Administration-based community health nurses completed surveys about content and timing of postdischarge interactions with home healthcare clinicians. We determined the types and frequency of medication errors among older Veterans receiving home healthcare, patient-provider communication patterns in this setting, and patient characteristics affecting medication error rates. Most Veterans (24/30, 80%) had at least one discordant medication, and only one noted that errors were identified and resolved. Veterans were asked about medications in the home healthcare setting, but far fewer were questioned about medication-taking details, adherence, and as-needed or nonoral medications. Higher numeracy was associated with fewer errors. Veterans Administration community health nurses reported contact by home healthcare clinicians in 41% of cases (7/17). Given the high rate of medication errors discovered, future work should focus on implementing best practices for medication review in this setting, as well as documenting barriers/facilitators of patient-provider communication.

Objective: Many patients with advanced serious illness or at the end of life experience delirium, a potentially reversible form of acute brain dysfunction, which may impair ability to participate in medical decision-making and to engage with their loved ones. Screening for delirium provides an opportunity to address modifiable causes. Unfortunately, delirium remains underrecognized. The main objective of this pilot was to validate the brief Confusion Assessment Method (bCAM), a two-minute delirium-screening tool, in a veteran palliative care sample., Method: This was a pilot prospective, observational study that included hospitalized patients evaluated by the palliative care service at a single Veterans' Administration Medical Center. The bCAM was compared against the reference standard, the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Both assessments were blinded and conducted within 30 minutes of each other., Result: We enrolled 36 patients who were a median of 67 years (interquartile range 63-73). The primary reasons for admission to the hospital were sepsis or severe infection (33%), severe cardiac disease (including heart failure, cardiogenic shock, and myocardial infarction) (17%), or gastrointestinal/liver disease (17%). The bCAM performed well against the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, for detecting delirium, with a sensitivity (95% confidence interval) of 0.80 (0.4, 0.96) and specificity of 0.87 (0.67, 0.96)., Significance of Results: Delirium was present in 27% of patients enrolled and never recognized by the palliative care service in routine clinical care. The bCAM provided good sensitivity and specificity in a pilot of palliative care patients, providing a method for nonpsychiatrically trained personnel to detect delirium.

Background: Identifying potential mechanisms that link depressed mood with worse health behaviors is important given the prevalence of depressed mood in patients with coronary heart disease (CHD) and its relationship with subsequent mortality. Perceived health competence is an individual's confidence in his/her ability to successfully engineer solutions to achieve health goals and may explain how depressed mood affects multiple health behaviors., Objective: Examine whether or not perceived health competence mediates the relationship between depressed mood and worse health behaviors., Design: A cross-sectional study conducted by the Patient-Centered Outcomes Research Institute-funded Mid-South Clinical Data Research Network between August 2014 and September 2015. Bootstrapped mediation was used., Participants: Patients with coronary heart disease (n = 2334)., Main Measures: Two items assessing perceived health competence, a single item assessing depressed mood, and a Health Behaviors Index including: the International Physical Activity Questionnaire (IPAQ); select items from the National Adult Tobacco Survey and the Alcohol Use Disorder Inventory Test; and single items assessing diet and medication adherence., Key Results: Depressed mood was associated with lower perceived health competence (a = - 0.21, p < .001) and lower perceived health competence was associated with worse performance on a Health Behaviors Index(b = 0.18, p < .001). Perceived health competence mediated the influence of depressed mood on health behaviors (ab = - 0.04, 95% CI = - 0.05 to - 0.03). The ratio of the indirect effect to the total effect was used as a measure of effect size (P M  = 0.26, 95% CI: 0.18 to 0.39)., Conclusions: Depressed mood is associated with worse health behaviors directly and indirectly via lower perceived health competence. Interventions to increase perceived health competence may lessen the deleterious impact of depressed mood on health behaviors and cardiovascular outcomes.