Rural-urban Differences in Long-term Mortality and Readmission Following COVID-19 Hospitalization, 2020 to 2023.

Background: We compared long-term mortality and readmission rates after COVID-19 hospitalization based on rural-urban status and assessed the impact of COVID-19 vaccination introduction on clinical outcomes by rurality. Methods: The study comprised adults hospitalized for COVID-19 at 17 hospitals in 4 US states between March 2020 and July 2022, followed until May 2023. The main analysis included all patients, whereas a sensitivity analysis focused on residents from 4 states containing 17 hospitals. Additional analyses compared the pre- and postvaccination periods. Results: The main analysis involved 9325 COVID-19 hospitalized patients: 31% were from 187 rural counties in 31 states; 69% from 234 urban counties in 44 states; the mean age was 65 years (rural, 66 years; urban, 64 years); 3894 women (rural, 41%; urban, 42%); 8007 Whites (rural, 87%; urban, 83%); 1738 deaths (rural, 21%; urban, 17%); and 2729 readmissions (rural, 30%; urban, 29%). During a median follow-up of 602 days, rural residence was associated with a 22% higher all-cause mortality (log-rank, P < .001; hazard ratio, 1.22; 95% confidence interval, 1.10-1.34, P < .001), and a trend toward a higher readmission rate (log-rank, P = .038; hazard ratio, 1.06; 95% confidence interval, .98-1.15; P = .130). The results remained consistent in the sensitivity analysis and in both pre- and postvaccination time periods. Conclusions and Relevance: Patients from rural counties experienced higher mortality and tended to be readmitted more frequently following COVID-19 hospitalization over the long term compared with those from urban counties, a difference that remained even after the introduction of COVID-19 vaccines.

Development and internal validation of machine learning-based models and external validation of existing risk scores for outcome prediction in patients with ischaemic stroke.

Aims: We developed new machine learning (ML) models and externally validated existing statistical models [ischaemic stroke predictive risk score (iScore) and totalled health risks in vascular events (THRIVE) scores] for predicting the composite of recurrent stroke or all-cause mortality at 90 days and at 3 years after hospitalization for first acute ischaemic stroke (AIS). Methods and results: In adults hospitalized with AIS from January 2005 to November 2016, with follow-up until November 2019, we developed three ML models [random forest (RF), support vector machine (SVM), and extreme gradient boosting (XGBOOST)] and externally validated the iScore and THRIVE scores for predicting the composite outcomes after AIS hospitalization, using data from 721 patients and 90 potential predictor variables. At 90 days and 3 years, 11 and 34% of patients, respectively, reached the composite outcome. For the 90-day prediction, the area under the receiver operating characteristic curve (AUC) was 0.779 for RF, 0.771 for SVM, 0.772 for XGBOOST, 0.720 for iScore, and 0.664 for THRIVE. For 3-year prediction, the AUC was 0.743 for RF, 0.777 for SVM, 0.773 for XGBOOST, 0.710 for iScore, and 0.675 for THRIVE. Conclusion: The study provided three ML-based predictive models that achieved good discrimination and clinical usefulness in outcome prediction after AIS and broadened the application of the iScore and THRIVE scoring system for long-term outcome prediction. Our findings warrant comparative analyses of ML and existing statistical method-based risk prediction tools for outcome prediction after AIS in new data sets.

An artificial intelligence approach for predicting death or organ failure after hospitalization for COVID-19: development of a novel risk prediction tool and comparisons with ISARIC-4C, CURB-65, qSOFA, and MEWS scoring systems.

BACKGROUND: We applied machine learning (ML) algorithms to generate a risk prediction tool [Collaboration for Risk Evaluation in COVID-19 (CORE-COVID-19)] for predicting the composite of 30-day endotracheal intubation, intravenous administration of vasopressors, or death after COVID-19 hospitalization and compared it with the existing risk scores. METHODS: This is a retrospective study of adults hospitalized with COVID-19 from March 2020 to February 2021. Patients, each with 92 variables, and one composite outcome underwent feature selection process to identify the most predictive variables. Selected variables were modeled to build four ML algorithms (artificial neural network, support vector machine, gradient boosting machine, and Logistic regression) and an ensemble model to generate a CORE-COVID-19 model to predict the composite outcome and compared with existing risk prediction scores. The net benefit for clinical use of each model was assessed by decision curve analysis. RESULTS: Of 1796 patients, 278 (15%) patients reached primary outcome. Six most predictive features were identified. Four ML algorithms achieved comparable discrimination (P > 0.827) with c-statistics ranged 0.849-0.856, calibration slopes 0.911-1.173, and Hosmer-Lemeshow P > 0.141 in validation dataset. These 6-variable fitted CORE-COVID-19 model revealed a c-statistic of 0.880, which was significantly (P < 0.04) higher than ISARIC-4C (0.751), CURB-65 (0.735), qSOFA (0.676), and MEWS (0.674) for outcome prediction. The net benefit of the CORE-COVID-19 model was greater than that of the existing risk scores. CONCLUSION: The CORE-COVID-19 model accurately assigned 88% of patients who potentially progressed to 30-day composite events and revealed improved performance over existing risk scores, indicating its potential utility in clinical practice.

Characteristics, Treatment Patterns, and Clinical Outcomes After Heart Failure Hospitalizations During the COVID-19 Pandemic, March to October 2020.

OBJECTIVE: To compare clinical characteristics, treatment patterns, and 30-day all-cause readmission and mortality between patients hospitalized for heart failure (HF) before and during the coronavirus disease 2019 (COVID-19) pandemic. PATIENTS AND METHODS: The study was conducted at 16 hospitals across 3 geographically dispersed US states. The study included 6769 adults (mean age, 74 years; 56% [5033 of 8989] men) with cumulative 8989 HF hospitalizations: 2341 hospitalizations during the COVID-19 pandemic (March 1 through October 30, 2020) and 6648 in the pre-COVID-19 (October 1, 2018, through February 28, 2020) comparator group. We used Poisson regression, Kaplan-Meier estimates, multivariable logistic, and Cox regression analysis to determine whether prespecified study outcomes varied by time frames. RESULTS: The adjusted 30-day readmission rate decreased from 13.1% (872 of 6648) in the pre-COVID-19 period to 10.0% (234 of 2341) in the COVID-19 pandemic period (relative risk reduction, 23%; hazard ratio, 0.77; 95% CI, 0.66 to 0.89). Conversely, all-cause mortality increased from 9.7% (645 of 6648) in the pre-COVID-19 period to 11.3% (264 of 2341) in the COVID-19 pandemic period (relative risk increase, 16%; number of admissions needed for one additional death, 62.5; hazard ratio, 1.19; 95% CI, 1.02 to 1.39). Despite significant differences in rates of index hospitalization, readmission, and mortality across the study time frames, the disease severity, HF subtypes, and treatment patterns remained unchanged (P>0.05). CONCLUSION: The findings of this large tristate multicenter cohort study of HF hospitalizations suggest lower rates of index hospitalizations and 30-day readmissions but higher incidence of 30-day mortality with broadly similar use of HF medication, surgical interventions, and devices during the COVID-19 pandemic compared with the pre-COVID-19 time frame.

How to promote a healthy lifestyle among schoolchildren: Development of an intervention module (i-PROMISe).

Objective: Lifestyle preferences are inculcated in childhood and once established, persist into adulthood. The Project PROMoting Health LIteracy in School (i-PROMISe) aims to promote a healthy lifestyle among students for the universal prevention of non-communicable diseases (NCDs) like diabetes. Study design: Qualitative study using focus-group-discussions (FGDs) and In-Depth Interviews (IDI). Method: Project was undertaken in two-phases in two private schools in New Delhi, India. In phase-one, FGDs with students (grades IV to VIII) and IDIs with teachers were conducted to ascertain their perceptions of diabetes prevention and management according to the Health Belief Model. The data was analyzed using a thematic framework method. In phase-two, the resources were pre-tested and participants' feedback was requested on the duration, quality, and understanding of the resources. Results: In total, 89 students and 17 teachers participated in phase-one (n = 54 [in FGDs] and n = 5 [in IDIs]) and phase-two (n = 35 students and n = 12 teachers in FGDs). In phase-one, themes that emerged included: diabetes was considered a disease of the elderly; misconceptions about susceptibility to these diseases were common; children were largely aware of measures to prevent these diseases, but barriers to adopting a healthy lifestyle existed. Based on the findings, a comprehensive module was developed, which consisted of a teacher's manual with interactive activities and short films. The resources (teacher's manual and short films) were well received and contributed to a better understanding of diabetes and other NCDs; myths/misconceptions were clarified. Conclusion: Development of resources using participatory approach can be effective in promoting and reinforcing healthy behaviours among school going children to prevent and control NCDs in schools.

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.

Hyperlipidaemia and mortality among patients hospitalised with pneumonia: retrospective cohort and propensity score matched study.

OBJECTIVE: To characterise the potential association of hyperlipidaemia (HLP) versus no HLP with all-cause mortality among patients hospitalised for pneumonia. DESIGN: Propensity score matched retrospective study. PARTICIPANTS: The study cohort consisted of consecutive 8553 adults hospitalised at a large academic centre with a discharge diagnosis of pneumonia from 1996 through 2015, followed until death or end of the study period, 17 August 2017. OUTCOMES: The outcome was HR for mortality at 28 days and in the long term in patients with pneumonia with concurrent HLP compared with those with no HLP. We first constructed multivariable Cox proportional regression models to estimate the association between concurrent HLP versus no HLP and mortality after pneumonia hospitalisation for the entire cohort. We then identified 1879 patients with pneumonia with concurrent HLP and propensity score matched in a 1:1 ratio to 1879 patients with no HLP to minimise the imbalance from measured covariates for further analysis. RESULTS: Among 8553 unmatched patients with pneumonia, concurrent HLP versus no HLP was independently associated with lower mortality at 28 days (HR 0.52, 95% CI 0.41 to 0.66) and at a median follow-up of 3.9 years (HR 0.75, 95% CI 0.70 to 0.80). The risk difference in mortality was consistent between 1879 propensity score matched pairs both at 28 days (HR 0.65, 95% CI 0.49 to 0.86) and at a median follow-up of 4 years (HR 0.88, 95% CI 0.81 to 0.96). In the subgroup of patients with clinically measured low-density lipoprotein cholesterol (LDL-C), graded inverse associations between LDL-C levels and mortality were found in both unmatched and matched cohorts. CONCLUSIONS: Among hospitalised patients with pneumonia, a diagnosis of HLP is protective against both short-term and long-term risk of death after adjustment for other major contributors to mortality in both unmatched and propensity score matched cohorts. These findings should be further investigated.

Initial and subsequent 3-year cost after hospitalization for first acute ischemic stroke and intracerebral hemorrhage.

AIMS: To examine 1) the major drivers of index hospitalization and 3-year post-acute follow-up care, 2) cost for rehabilitation and homecare, and 3) indirect cost from lost productivity after acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH). METHODS: Retrospective study of adults hospitalized with AIS (n = 811) and ICH (N = 145) between 2003 and 2014. Direct costs standardized to Medicare reimbursement rates were captured for hospitalization and 3-year follow-up or death. Adjusted cost estimates were assessed using generalized linear modeling with gamma distribution. Costs for rehabilitation, home healthcare, and lost productivity were assessed using sets of cost captured through literature review. RESULTS: Calculated as mean cost per person: hospitalization $18,154 for AIS and $24,077 for ICH; monthly 3-year aggregate $5138 for AIS and $8172 for ICH; 3-year inpatient rehabilitation $4185 for AIS and $4196 for ICH; homecare $19,728 for AIS and $14,487 for ICH; indirect cost from lost productivity $77,078 for AIS and $56,601 for ICH. Age < 55 years, being non-white, and stroke severity were strongly associated with greater hospitalization cost for AIS and ICH. Hyperlipidemia incurred lower while cancer, coronary artery disease, asthma/chronic obstructive pulmonary disease, heart failure, and anemia incurred higher 3-year aggregate cost for AIS. Cancer and diabetes mellitus incurred higher 3-year aggregate cost for ICH. CONCLUSIONS: We provide estimates of direct and indirect costs incurred for acute and continuing post-acute care through a 3-year follow-up period after first-ever AIS and ICH with important comparisons for predictors between index hospitalization and 3-year post-stroke costs.

Effect of insulin sensitizer therapy on amino acids and their metabolites.

AIMS: Prior studies have reported that elevated concentrations of several plasma amino acids (AA), particularly branched chain (BCAA) and aromatic AA predict the onset of type 2 diabetes. We sought to test the hypothesis that circulating BCAA, aromatic AA and related AA metabolites decline in response to the use of insulin sensitizing agents in overweight/obese adults with impaired fasting glucose or untreated diabetes. METHODS: We performed a secondary analysis of a randomized, double-blind, placebo, controlled study conducted in twenty five overweight/obese (BMI ~30kg/m(2)) adults with impaired fasting glucose or untreated diabetes. Participants were randomized to three months of pioglitazone (45mg per day) plus metformin (1000mg twice per day, N=12 participants) or placebo (N=13). We measured insulin sensitivity by the euglycemic-hyperinsulinemic clamp and fasting concentrations of AA and AA metabolites using ultra-pressure liquid chromatography tandem mass spectrometry before and after the three-month intervention. RESULTS: Insulin sensitizer therapy that significantly enhanced insulin sensitivity reduced 9 out of 33 AA and AA metabolites measured compared to placebo treatment. Moreover, insulin sensitizer therapy significantly reduced three functionally clustered AA and metabolite pairs: i) phenylalanine/tyrosine, ii) citrulline/arginine, and iii) lysine/α-aminoadipic acid. CONCLUSIONS: Reductions in plasma concentrations of several AA and AA metabolites in response to three months of insulin sensitizer therapy support the concept that reduced insulin sensitivity alters AA and AA metabolites.

Cohort study on radioactive iodine-induced hypothyroidism: implications for Graves' ophthalmopathy and optimal timing for thyroid hormone assessment.

BACKGROUND: Graves' ophthalmopathy (GO) develops or worsens in up to one-third of patients treated with radioactive iodine (RAI) for Graves' hyperthyroidism. We sought to identify the prevalence of development or worsening of GO in patients treated with RAI for Graves' hyperthyroidism and to identify the risk factors associated with that outcome. METHODS: We identified a retrospective cohort of consecutive patients treated with RAI at Mayo Clinic (Rochester, MN) between 2005 and 2006. We assessed their medical records for evidence of hypothyroidism and development or worsening of GO in the year after therapy. Hypothyroidism was defined as thyrotropin >3.0 mIU/L or free thyroxine <0.8 ng/dL. RESULTS: We identified 291 consecutive patients who received RAI therapy during the study period, with 195 out of 291 having complete follow-up data for a one-year period. GO was present in 46 out of 195 patients (23.6%) at baseline. After RAI treatment, GO developed or worsened in 25 out of 195 patients (12.8%) and it was associated with hypothyroidism at first follow-up (p=0.011) with an odds ratio (OR) of 3.3 [95% confidence interval (CI) 1.3-8.7]. More smokers than nonsmokers developed new or worse GO (17.7% vs. 11.8%), but that difference did not reach statistical significance (p=0.35). Preexisting GO (24% of patients) was associated with a higher risk for negative GO outcome compared with patients who had no GO at baseline (11%; p=0.021). Both development of hypothyroidism by the first visit after RAI therapy (OR 3.6) and preexistent GO (OR 2.8) remained significant in a multivariate analysis. Development of hypothyroidism was more likely in patients with longer duration to first follow-up (p<0.001). By 6-8 weeks after RAI treatment, the prevalence of hypothyroidism was ∼40%, while that of hyperthyroidism was only 20%. CONCLUSIONS: The presence of hypothyroidism at the first assessment of thyroid function after RAI administration is a strong predictor for adverse GO outcome. This risk is highest in patients with preexisting GO. We suggest that in order to prevent clinical hypothyroidism and the associated risk for GO, the optimal time for first measurement of fT4 is before 6 weeks after RAI therapy.

Measurement of human skeletal muscle oxidative capacity by 31P-MR spectroscopy: a cross-validation with in vitro measurements.

PURPOSE: To cross-validate skeletal muscle oxidative capacity measured by (31)P-MR spectroscopy with in vitro measurements of oxidative capacity in mitochondria isolated from muscle biopsies of the same muscle group in 18 healthy adults. MATERIALS AND METHODS: Oxidative capacity in vivo was determined from PCr recovery kinetics following a 30-s maximal isometric knee extension. State 3 respiration was measured in isolated mitochondria using high-resolution respirometry. A second cohort of 10 individuals underwent two (31)P-MRS testing sessions to assess the test-retest reproducibility of the method. RESULTS: Overall, the in vivo and in vitro methods were well-correlated (r = 0.66-0.72) and showed good agreement by Bland Altman plots. Excellent reproducibility was observed for the PCr recovery rate constant (CV = 4.6%; ICC = 0.85) and calculated oxidative capacity (CV = 3.4%; ICC = 0.83). CONCLUSION: These results indicate that (31)P-MRS corresponds well with gold-standard in vitro measurements and is highly reproducible.

Using quality-improvement techniques to enhance patient education and counselling of diagnosis and management.

BACKGROUND: Patients recall less than half the information provided to them by their physicians. AIMS: The aim of this study was to use quality-improvement (QI) techniques to enhance patient understanding of diagnosis, management and follow-up at the end of the office visit. METHOD: QI techniques including stakeholder analysis, process mapping and plan-do-study-act (PDSA) cycles were used in a pilot study in an outpatient endocrinology clinic specialising in bone disease. The impact of these interventions was evaluated by pre- and post-intervention patient surveys that included qualitative and quantitative data. RESULTS: A team of endocrinology fellows and faculty with expertise in QI developed a series of tools to encourage conversation and interaction during the encounter and to serve as a reference for patients to take home through five PDSA cycles. The tools were iterations of written materials provided to patients at the end of the clinical encounter. In each cycle, the tools were modified according to feedback from patients and providers. Ninety-three patients participated in this study. Patients were surveyed after the implementation of two of the five cycles. Compared with pre-intervention, modifications during the two cycles were associated with a non-significant increase in patients' understanding of the reasons for testing (from 64% to 80% and 75%); management plan (from 61% to 86% and 79%); and future follow-up plans (from 64% to 86% and 81%); P > 0.05 for all three outcomes. Improvement was not seen in patients' knowledge of their diagnoses (from 74% to 73% and 70%; P > 0.05). CONCLUSION: This pilot study shows how QI tools can be used for creating and initiating system improvements aimed at enhancing patient education and counselling.

Dehydroepiandrosterone in adrenal insufficiency and ageing.

PURPOSE OF REVIEW: The physiological role of dehydroepiandrosterone remains unclear, and there is continuing controversy on whether dehydroepiandrosterone treatment benefits adrenal-deficient and elderly people with an age-related decline in dehydroepiandrosterone. The objective of this study is to critically review published results and determine whether there is a valid case for dehydroepiandrosterone treatment with advancing age and hypoadrenalism. RECENT FINDINGS: Oral dehydroepiandrosterone therapy in both elderly and hypoadrenal subjects achieves dehydroepiandrosterone levels comparable to young subjects. Long-term dehydroepiandrosterone replacement in elderly people demonstrated no improvement in body composition, physical performance or any metabolic parameters; however, a modest but inconsistent improvement in bone mineral density occurred at certain sites. Dehydroepiandrosterone replacement in hypoadrenalism modestly improved insulin sensitivity and altered the lipid profile, but it remains uncertain whether these changes improve any patient-important outcomes. Dehydroepiandrosterone replacement in adrenal deficiency inconsistently improves some aspects of mental health. SUMMARY: Dehydroepiandrosterone replacement increases bone mineral density in elderly subjects; however, the effect is relatively small compared with established therapies for osteoporosis. No additional benefits have been identified for long-term dehydroepiandrosterone replacement, when used in the elderly to prevent or delay ageing. Dehydroepiandrosterone replacement may improve some metabolic variables and measures of psychological well-being in adrenal deficiency, but these benefits are not consistently sustained in long-term therapy. Long-term studies are needed to confirm sustained benefits in adrenal deficiency and establish long-term safety.

Systematic evaluation of the quality of randomized controlled trials in diabetes.

OBJECTIVE: We sought to systematically ascertain the quality of randomized controlled trials (RCTs) in diabetes. RESEARCH DESIGN AND METHODS: We identified the 10 most recently published trials as of 31 October 2003 in each of six general medical, five diabetes, and five metabolism and nutrition journals and further enriched our sample with 10 additional RCTs from each of five journals that published the most eligible RCTs in a year. We explored the association between trial characteristics and reporting quality using univariate analyses and a preplanned multivariate regression model. RESULTS: After excluding redundant reports of included trials and one trial that measured outcomes on the health system and not on patients, we included 199 RCTs: 119 assessed physiological and other laboratory outcomes, 42 assessed patient-important outcomes (e.g., morbidity and mortality, quality of life), and 38 assessed surrogate outcomes (e.g., disease progression or regression, HbA(1c), cholesterol). Fifty-three percent were of low methodological quality, as were one-third (36-40%) of trials reporting patient-important or surrogate outcomes and two-thirds (64%) of laboratory investigations. Independent predictors of low quality were nonprofit funding source (odds ratio 3.1 [95% CI 1.5-6.2]), measure of physiological and laboratory outcomes (2.3 [1.2-4.4]), and cross-over design (2.3 [1.1-4.8]), all characteristics of laboratory clinical investigations. CONCLUSIONS: There is ample room for improving the quality of diabetes trials. To enhance the practice of evidence-based diabetes care, trialists need to pay closer attention to the rigorous implementation and reporting of important methodological safeguards against bias in randomized trials.