Shorter-acting glucagon-like peptide-1 receptor agonists are associated with increased development of gastro-oesophageal reflux disease and its complications in patients with type 2 diabetes mellitus: a population-level retrospective matched cohort study.

BACKGROUND: Shorter half-life glucagon-like peptide-1 receptor agonists (GLP-1 RAs) delay gastric emptying (DGE) more than GLP-1 RAs with longer half-lives. DGE is a known risk factor for gastro-oesophageal reflux disease (GERD) and its complications. AIM: To determine whether short-acting or long-acting GLP-1 RAs are associated with an increased risk of new GERD or GERD-related complications DESIGN: We used the TriNetX global database to identify adult patients with type 2 diabetes mellitus and generated two cohorts totalling 1 543 351 patients on (1) GLP-1 RA or (2) other second-line diabetes medication. Using propensity-score matching, Kaplan-Meier Analysis and Cox-proportional hazards ratio (HR), we analysed outcomes and separately examined outcomes in patients starting short-acting (≤1 day) and long-acting (≥5 days) GLP-1 RAs. RESULTS: 177 666 patients were in each propensity-matched cohort. GLP-1 RA exposure was associated with an increased risk (HR 1.15; 95% CI 1.09 to 1.22) of erosive reflux disease (ERD). However, this was solely due to short-acting (HR 1.215; 95% CI 1.111 to 1.328), but not long-acting (HR 0.994; 95% CI 0.924 to 1.069) GLP-1 RA exposure. Short-acting GLP-1 RAs were also associated with increased risk of oesophageal stricture (HR 1.284; 95% CI 1.135 to 1.453), Barrett's without dysplasia (HR 1.372; 95% CI 1.217 to 1.546) and Barrett's with dysplasia (HR 1.505; 95% CI 1.164 to 1.946) whereas long-acting GLP-1 RAs were not. This association persisted in sensitivity analyses, and when individually examining the short-acting GLP-1 RAs liraglutide, lixisenatide and exenatide. CONCLUSION: Starting shorter-acting GLP-1 RAs is associated with increased risks of GERD and its complications.

Reducing Racial Disparities in the Timeliness of Potential Lung Cancer Evaluation With a Novel Application-Supported Rapid Outpatient Diagnostic Program: An Interrupted Time Series Analysis.

INTRODUCTION: Rapid outpatient diagnostic programs (RODP) expedite lung cancer evaluation, but their impact on racial disparities in the timeliness of evaluation is less clear. MATERIALS AND METHODS: This was a retrospective analysis of the impact of an internally developed application-supported RODP on racial disparities in timely referral completion rates for patients with potential lung cancer at a safety-net healthcare system. An application screened referrals to pulmonology for indications of lung mass or nodule and presented relevant clinical information that enabled dedicated pulmonologists to efficiently review and triage cases according to urgency. Subsequent care coordination was overseen by a dedicated nurse coordinator. To determine the program's impact, we conducted an interrupted time series analysis of the monthly fraction of referrals completed within 30 days, stratified by those identified as White, non-Hispanic and those that were not (racial and ethnic minorities). RESULTS: There were 902 patients referred in the 2 years preintervention and 913 in the 2 years postintervention. Overall, the median age was 63 years, and 44.7% of referred patients were female. 44.2% were White, non-Hispanic while racial and ethnic minorities constituted 54.3%. After the intervention, there was a significant improvement in the proportion of referrals completed within 30 days (62.4% vs. 48.2%, P <.01). The interrupted time series revealed a significant immediate improvement in timely completion among racial and ethnic minorities (23%, P < .01) that was not reflected in the majority White, non-Hispanic subgroup (11%, not significant). CONCLUSION: A thoughtfully designed and implemented RODP reduced racial disparities in the timely evaluation of potential lung cancer.

Neighborhood and racial influences on triple negative breast cancer: evidence from Northeast Ohio.

PURPOSE: Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with higher recurrence rates and poorer prognoses and most prevalent among non-Hispanic Black women. Studies of multiple health conditions and care processes suggest that neighborhood socioeconomic position is a key driver of health disparities. We examined roles of patients' neighborhood-level characteristics and race on prevalence, stage at diagnosis, and mortality among patients diagnosed with BC at a large safety-net healthcare system in Northeast Ohio. METHODS: We used tumor registry to identify BC cases from 2007 to 2020 and electronic health records and American Community Survey for individual- and area-level factors. We performed multivariable regression analyses to estimate associations between neighborhood-level characteristics, measured by the Area Deprivation Index (ADI), race and comparative TNBC prevalence, stage at diagnosis, and total mortality. RESULTS: TNBC was more common among non-Hispanic Black (53.7%) vs. non-Hispanic white patients (46.4%). Race and ADI were individually significant predictors of TNBC prevalence, stage at diagnosis, and total mortality. Race remained significantly associated with TNBC subtype, adjusting for covariates. Accounting for TNBC status, a more disadvantaged neighborhood was significantly associated with a worse stage at diagnosis and higher death rates. CONCLUSION: Our findings suggest that both neighborhood socioeconomic position and race are strongly associated with TNBC vs. other BC subtypes. The burden of TNBC appears to be highest among Black women in the most socioeconomically disadvantaged neighborhoods. Our study suggests a complex interplay of social conditions and biological disease characteristics contributing to racial disparities in BC outcomes.

Association of hypothyroidism with outcomes in hospitalized adults with COVID-19: Results from the International SCCM Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is associated with high rates of morbidity and mortality. Primary hypothyroidism is a common comorbid condition, but little is known about its association with COVID-19 severity and outcomes. This study aims to identify the frequency of hypothyroidism in hospitalized patients with COVID-19 as well as describe the differences in outcomes between patients with and without pre-existing hypothyroidism using an observational, multinational registry. METHODS: In an observational cohort study we enrolled patients 18 years or older, with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between March 2020 and February 2021. The primary outcomes were (1) the disease severity defined as per the World Health Organization Scale for Clinical Improvement, which is an ordinal outcome corresponding with the highest severity level recorded during a patient's index COVID-19 hospitalization, (2) in-hospital mortality and (3) hospital-free days. Secondary outcomes were the rate of intensive care unit (ICU) admission and ICU mortality. RESULTS: Among the 20,366 adult patients included in the study, pre-existing hypothyroidism was identified in 1616 (7.9%). The median age for the Hypothyroidism group was 70 (interquartile range: 59-80) years, and 65% were female and 67% were White. The most common comorbidities were hypertension (68%), diabetes (42%), dyslipidemia (37%) and obesity (28%). After adjusting for age, body mass index, sex, admission date in the quarter year since March 2020, race, smoking history and other comorbid conditions (coronary artery disease, hypertension, diabetes and dyslipidemia), pre-existing hypothyroidism was not associated with higher odds of severe disease using the World Health Organization disease severity index (odds ratio [OR]: 1.02; 95% confidence interval [CI]: 0.92, 1.13; p = .69), in-hospital mortality (OR: 1.03; 95% CI: 0.92, 1.15; p = .58) or differences in hospital-free days (estimated difference 0.01 days; 95% CI: -0.45, 0.47; p = .97). Pre-existing hypothyroidism was not associated with ICU admission or ICU mortality in unadjusted as well as in adjusted analysis. CONCLUSIONS: In an international registry, hypothyroidism was identified in around 1 of every 12 adult hospitalized patients with COVID-19. Pre-existing hypothyroidism in hospitalized patients with COVID-19 was not associated with higher disease severity or increased risk of mortality or ICU admissions. However, more research on the possible effects of COVID-19 on the thyroid gland and its function is needed in the future.

Mechanisms of socioeconomic differences in COVID-19 screening and hospitalizations.

BACKGROUND: Social and ecological differences in early SARS-CoV-2 pandemic screening and outcomes have been documented, but the means by which these differences have arisen are not well understood. OBJECTIVE: To characterize socioeconomic and chronic disease-related mechanisms underlying these differences. DESIGN: Observational cohort study. SETTING: Outpatient and emergency care. PATIENTS: 12900 Cleveland Clinic Health System patients referred for SARS-CoV-2 testing between March 17 and April 15, 2020. INTERVENTIONS: Nasopharyngeal PCR test for SARS-CoV-2 infection. MEASUREMENTS: Test location (emergency department, ED, vs. outpatient care), COVID-19 symptoms, test positivity and hospitalization among positive cases. RESULTS: We identified six classes of symptoms, ranging in test positivity from 3.4% to 23%. Non-Hispanic Black race/ethnicity was disproportionately represented in the group with highest positivity rates. Non-Hispanic Black patients ranged from 1.81 [95% confidence interval: 0.91-3.59] times (at age 20) to 2.37 [1.54-3.65] times (at age 80) more likely to test positive for the SARS-CoV-2 virus than non-Hispanic White patients, while test positivity was not significantly different across the neighborhood income spectrum. Testing in the emergency department (OR: 5.4 [3.9, 7.5]) and cardiovascular disease (OR: 2.5 [1.7, 3.8]) were related to increased risk of hospitalization among the 1247 patients who tested positive. LIMITATIONS: Constraints on availability of test kits forced providers to selectively test for SARS-Cov-2. CONCLUSION: Non-Hispanic Black patients and patients from low-income neighborhoods tended toward more severe and prolonged symptom profiles and increased comorbidity burden. These factors were associated with higher rates of testing in the ED. Non-Hispanic Black patients also had higher test positivity rates.

On the Front (Phone) Lines: Results of a COVID-19 Hotline.

BACKGROUND: Severe acute respiratory syndrome coronavirus (SARS-CoV-2) and the associated coronavirus disease of 2019 (COVID-19) have presented immense challenges for health care systems. Many regions have struggled to adapt to disruptions to health care practice and use systems that effectively manage the demand for services. METHODS: This was a cohort study using electronic health records at a health care system in northeast Ohio that examined the effectiveness of the first 5 weeks of a 24/7 physician-staffed COVID-19 hotline including social care referrals for patients required to self-isolate. We describe clinical diagnosis, patient characteristics (age, sex race/ethnicity, smoking status, insurance status), and visit disposition. We use logistic regression to evaluate associations between patient characteristics, visit disposition and subsequent emergency department use, hospitalization, and SARS-Cov-2 PCR testing. PARTICIPANTS: In 5 weeks, 10,112 patients called the hotline (callers). Of these, 4213 (42%) were referred for a physician telehealth visit (telehealth patients). Mean age of callers was 42 years; 67% were female, 51% white, and 46% were on Medicaid/uninsured. RESULTS: Common caller concerns included cough, fever, and shortness of breath. Most telehealth patients (79%) were advised to self-isolate at home, 14% were determined to be unlikely to have COVID-19, 3% were advised to seek emergency care, and 4% had miscellaneous other dispositions. A total of 287 patients (7%) had a subsequent emergency department visit, and 44 (1%) were hospitalized with a COVID-19 diagnosis. Of the callers, 482 (5%) had a COVID-19 test reported, with 69 (14%) testing positive. Among patients advised to stay at home, 83% had no further face-to-face visits. In multivariable results, only a physician recommendation to seek emergency care was associated with emergency department use (odds ratio = 4.73, 95% confidence interval = 1.37-16.39, P = .014). Only older age was associated with having a positive test result. Patients with social needs and interest in receiving help were offered services to meet their needs including food deliveries (n = 92), behavioral health telephone visits (n = 49), and faith-based comfort calls from pastoral care personnel (n = 37). CONCLUSIONS AND RELEVANCE: Robust, physician-directed telehealth services can meet a wide range of clinical and social needs during the acute phase of a pandemic, conserving scarce resources such as personal protective equipment and testing supplies and preventing the spread of infections to patients and health care workers.

Assessing Different Approaches to Leveraging Historical Smoking Exposure Data to Better Select Lung Cancer Screening Candidates: A Retrospective Validation Study.

INTRODUCTION: There is mounting interest in the use of risk prediction models to guide lung cancer screening. Electronic health records (EHRs) could facilitate such an approach, but smoking exposure documentation is notoriously inaccurate. While the negative impact of inaccurate EHR data on screening practices reliant on dichotomized age and smoking exposure-based criteria has been demonstrated, less is known regarding its impact on the performance of model-based screening. AIMS AND METHODS: Data were collected from a cohort of 37 422 ever-smokers between the ages of 55 and 74, seen at an academic safety-net healthcare system between 1999 and 2018. The National Lung Cancer Screening Trial (NLST) criteria, PLCOM2012 and LCRAT lung cancer risk prediction models were validated against time to lung cancer diagnosis. Discrimination (area under the receiver operator curve [AUC]) and calibration were assessed. The effect of substituting the last documented smoking variables with differentially retrieved "history conscious" measures was also determined. RESULTS: The PLCOM2012 and LCRAT models had AUCs of 0.71 (95% CI, 0.69 to 0.73) and 0.72 (95% CI, 0.70 to 0.74), respectively. Compared with the NLST criteria, PLCOM2012 had a significantly greater time-dependent sensitivity (69.9% vs. 64.5%, p < .01) and specificity (58.3% vs. 56.4%, p < .001). Unlike the NLST criteria, the performances of the PLCOM2012 and LCRAT models were not prone to historical variability in smoking exposure documentation. CONCLUSIONS: Despite the inaccuracies of EHR-documented smoking histories, leveraging model-based lung cancer risk estimation may be a reasonable strategy for screening, and is of greater value compared with using NLST criteria in the same setting. IMPLICATIONS: EHRs are potentially well suited to aid in the risk-based selection of lung cancer screening candidates, but healthcare providers and systems may elect not to leverage EHR data due to prior work that has shown limitations in structured smoking exposure data quality. Our findings suggest that despite potential inaccuracies in the underlying EHR data, screening approaches that use multivariable models may perform significantly better than approaches that rely on simpler age and exposure-based criteria. These results should encourage providers to consider using pre-existing smoking exposure data with a model-based approach to guide lung cancer screening practices.

Neighborhood Disadvantage and Lung Cancer Incidence in Ever-Smokers at a Safety Net Health-Care System: A Retrospective Study.

BACKGROUND: Neighborhood circumstances have an influence on multiple health outcomes, but the association between neighborhood conditions and lung cancer incidence has not been studied in sufficient detail. The goal of this study was to understand whether neighborhood conditions are independently associated with lung cancer incidence in ever-smokers after adjusting for individual smoking exposure and other risk factors. METHODS: A cohort of ever-smokers aged ≥ 55 years was assembled from 19 years of electronic health record data from our academic community health-care system. Patient demographic characteristics and other measures known to be associated with lung cancer were ascertained. Patient addresses at their index visit were geocoded to the census block group level to determine the area deprivation index (ADI), drawn from 5-year estimates from the American Community Survey. A multivariate Cox proportional hazards model was fit to assess the association between ADI and time to lung cancer diagnosis. Tests of statistical significance were two-sided. RESULTS: The study included 19,867 male subjects and 21,748 female subjects. Fifty-three percent of the patients were white, 38% were black, and 5% were Hispanic. Of these, 1,149 developed lung cancer. After adjusting for known risk factors, patients residing in the most disadvantaged areas had a significantly increased incidence of lung cancer compared with those in the least disadvantaged areas (hazard ratio, 1.29; 95% CI 1.07-1.55). CONCLUSIONS: Census-derived estimates of neighborhood conditions have a powerful association with lung cancer incidence, even when adjusting for individual variables. Further research investigating the mechanisms that link neighborhood conditions to lung cancer is warranted.

Can an anterior quadriceps release improve range of motion in the stiff arthritic knee?

We hypothesize that tethering adhesions of the quadriceps muscle are the major pathological structures responsible for a limited range of motion in the stiff arthritic knee. Forty-two modified quadriceps muscle releases were performed on 24 patients with advanced osteoarthritis scheduled for total knee arthroplasty. The ranges of motion were documented intraoperatively both before and immediately after the release. Passive flexion improved significantly in all patients (mean, 32.4 degrees of improvement, P < .001) following a modified quadriceps release, despite any presence of osteophytes or severe deformities. These results strongly implicate adhesions of the quadriceps muscle to the underlying femur, which prevent the distal excursion of the quadriceps tendon, as the restrictive pathology preventing deep flexion in patients with osteoarthritis.