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ObjectiveTo 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 methodsThe 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.ResultsThe 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).ConclusionThe 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.

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.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.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.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.

ObjectiveTo characterise the potential association of hyperlipidaemia (HLP) versus no HLP with all-cause mortality among patients hospitalised for pneumonia.DesignPropensity score matched retrospective study.ParticipantsThe 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.OutcomesThe 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.ResultsAmong 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.ConclusionsAmong 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.

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).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.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.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.

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 ~ 30 kg/m2) adults with impaired fasting glucose or untreated diabetes. Participants were randomized to three months of pioglitazone (45 mg per day) plus metformin (1000 mg 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.

Mitochondria are widely recognized for their ability to generate chemical energy to fuel cellular energy requirements. In metabolically active tissues such as skeletal muscle, the abundance and function of these organelles correlates with physical performance (1). More recently there has been growing interest in understanding how these organelles are involved in the etiology or pathophysiology of many human diseases such as type 2 diabetes (2), obesity (3), heart failure (4), stroke (5), and Alzheimer’s Disease (6). Historically, mitochondrial function in human skeletal muscle has been estimated from activities of marker enzymes (7) or from direct measurements of oxygen consumption (8) or ATP production rates (9) in tissues or isolated mitochondria. Muscle biopsy specimens also permit measurements of mRNA, DNA, and protein expression measurements. In spite of the wealth of information afforded by in vitro measurements from biopsy tissue, practical and ethical considerations limit the frequency and location of tissue biopsies as well as subject populations such as children or frail elderly. Since Chance and colleagues pioneered the use of phosphorous magnetic resonance spectroscopy (31P-MRS) for in vivo assessment of human skeletal muscle metabolism (10), this non-invasive technology has become widespread. The capability for non-invasive assessment of skeletal muscle oxidative capacity holds appeal for investigators who desire an in vivo measurement that can be performed repeatedly with minimal risk to participants. Skeletal muscle oxidative capacity may be measured in vivo using 31P-MRS by monitoring the recovery of phosphocreatine (PCr) following prior depletion by a stimulus such as exercise. Through the equilibrium of the creatine kinase reaction, post-exercise PCr resynthesis is a function of mitochondrial ATP production. Thus, the rate constant of PCr recovery (kPCr) is proportional to muscle mitochondrial oxidative capacity, calculated as the product of kPCr and PCr concentration in resting skeletal muscle (11–13). This kinetic analysis has been found to be reproducible (14–16)and well-correlated with citrate synthase activity measured in vitro (17,18), whole body oxygen uptake (16–20), and theoretical models (17,21). In spite of good agreement between 31P-MRS and mitochondrial enzyme activity, to our knowledge there have been no comparisons of skeletal muscle oxidative capacity measured by 31P-MRS and more direct in vitro measurements of mitochondrial oxidative capacity. An evaluation of the level of agreement between 31P-MRS and gold-standard in vitro measurements of skeletal muscle oxidative capacity would help establish 31P-MRS as a valuable tool in research and clinical settings. In the present study we cross-validated skeletal muscle oxidative capacity measured by 31P-MRS and by high-resolution respirometry of mitochondria isolated from muscle biopsy tissue. We also assessed the test-retest reliability of oxidative capacity measured by 31P-MRS.

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.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.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.

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.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 thyrotropin3.0 mIU/L or free thyroxine0.8 ng/dL.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 (p0.001). By 6-8 weeks after RAI treatment, the prevalence of hypothyroidism was ∼40%, while that of hyperthyroidism was only 20%.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.

Patients recall less than half the information provided to them by their physicians.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.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.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%); P0.05 for all three outcomes. Improvement was not seen in patients' knowledge of their diagnoses (from 74% to 73% and 70%; P0.05).This pilot study shows how QI tools can be used for creating and initiating system improvements aimed at enhancing patient education and counselling.

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, HbA1c, 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.

Source Citation Gillies CL, Abrams KR, Lambert PC, et al. Pharmacological and lifestyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: systematic revie...