Association of Serum Thyroxine and Atrial Fibrillation in Patients on Levothyroxine.

INTRODUCTION: Excess thyroid hormone is a well-documented risk factor for the development of atrial fibrillation (AF). The purpose of the study is to assess incidence of AF in patients taking levothyroxine for hypothyroidism and correlate it with biochemical thyroid function. MATERIALS AND METHODS: This was a retrospective cohort study of patients aged 18 years and older who were treated with levothyroxine. Exclusion criteria were pre-existing diagnosis of AF and use of amiodarone in the prior year. Patients were followed 2012 through 2019 and stratified into 4 groups based on mean thyroid-stimulating hormone (TSH) value or mean fT4 value in 2012. Primary outcome was incidence of AF. Rates of AF between groups were assessed via Poisson regression with control of underlying confounders. RESULTS: Of 21,035 patients, 1091 (5.2%) developed AF during follow-up. Thyroid-stimulating hormone at baseline was not significantly associated with incident AF. Higher fT4 levels at baseline were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio 1.22; 95% CI, 1.03-1.44) for the highest quartile versus the lowest quartile of fT4. CONCLUSIONS: In hypothyroid patients treated with levothyroxine, higher circulating fT4 levels are associated with increased risk of incident AF. There is no association of serum TSH with risk of AF. In patients at risk for AF, consideration should be given to avoiding fT4 levels in the highest quartile.

Identifying Risk Factors for Cardiovascular Events Among Active-Duty Service Members and Veterans Prescribed Nonsteroidal Anti-Inflammatory Drugs (NSAIDs).

Background: Oral NSAIDs are widely used analgesic medications for the treatment of musculoskeletal and inflammatory conditions. NSAIDs are associated with adverse effects that arise from COX enzyme inhibition including cardiovascular events. The combined role of patient and prescription factors associated with NSAID use on cardiovascular risk is not well characterized. Objective: The purpose of this study is to identify the risk factors with cardiovascular events among NSAID users. Methods: This study is a retrospective, nested case-control study, within the DAVINCI database, among active-duty service members and veterans with at least one NSAID pharmacy claim between fiscal year (FY) 2015-FY2020. Inclusion criteria individuals ≥18 years of age received a prescription NSAID for ≥7-day supply and a duration ≥1 month overall. Cases experienced nonfatal myocardial infarction, nonfatal stroke, or new onset heart failure. Ten controls were selected per case. Risk factors were identified through logistic regression modeling. Results: The risk factors with strongest association to the primary outcome included age starting at 45 up to 75 and older, the first 90 days of NSAID exposure, cerebrovascular disease, cardiomyopathy, and history of myocardial infarction. Cox-selectivity and dose did not appear to be clinically significant in their association with cardiovascular events. Conclusion: The results of this study indicate that age, initial NSAID exposure, and comorbidities are more predictive than NSAID-specific factors such as COX-selectivity and dose. The results provide the framework for development of a risk score to improve prediction of NSAID-associated cardiovascular events.

Relationship Between Body Mass Index and Diagnosis of Obesity in the Military Health System Active Duty Population.

OBJECTIVE: The overall rate of obesity is rising in the USA; this is also reflected in the military population. It is important that providers appropriately diagnose obesity and discuss treatment options with their patients.The purpose of this study was to investigate diagnosis of obesity compared to documented body mass index (BMI) in the military health system. METHODS: Institutional review board approval was obtained by the 59th Medical Wing (Lackland Air Force Base, Texas) as an exempt study. This study included active duty military service members aged 18-65 years who sought outpatient care at a military treatment facility from September 2013 to August 2018 with a weight within the range of 31.8-226.8 kg and height between 121.9 and 215.9 cm. Data were collected from the Clinical Data Repository vitals and M2 encounter data to determine the percentage of each sub-population with a diagnosis of obesity according to BMI (≥30 kg/m2) and International Classification of Diseases diagnosis codes. RESULTS: Using BMI, 19.2% of female and 26.8% of male service members can be diagnosed with obesity; however, only 42.2% and 35.1%, respectively, with a BMI ≥30 was diagnosed as such. This discrepancy was consistent among all service branches and BMI ranges. CONCLUSION: This study demonstrates that obesity is underdiagnosed compared to BMI. This may result in insufficient resources being provided to patients to reduce weight. Further investigation is warranted to identify causes of underdiagnosis and potential barriers to diagnosis.

Neutral effect of exenatide on serum testosterone in men with type 2 diabetes mellitus: A prospective cohort.

BACKGROUND: Endogenous testosterone increases with weight loss from diet, exercise, and bariatric surgery. However, little is known about testosterone levels after weight loss from medication. OBJECTIVES: Uncover the effects of Glucagon-Like Peptide-1 receptor agonist (GLP-1 RA) therapy on serum testosterone. MATERIAL AND METHODS: Prospective cohort study of men starting GLP-1 RA therapy for type 2 diabetes mellitus. RESULTS: 51 men lost 2.27 kg (p = 0.00162) and their HbA1c values improved by 0.7% (p = 0.000503) after 6 months of GLP-1 RA therapy. There was no significant change in testosterone for the group as a whole. However, in subgroup analyses, there was a significant difference in total testosterone change between men starting with baseline total testosterone <320 ng/dL (238.5 ± 56.5 ng/dL to 272.2 ± 82.3 ng/dL) compared to higher values (438 ± 98.2 ng/dL to 412 ± 141.2 ng/dL) (p = 0.0172);free testosterone increased if the baseline total testosterone was <320 ng/dL (55.2 ± 12.8 pg/mL to 57.2 ± 17.6 pg/mL) and decreased if >320 ng/dL (74.7 ± 16.3 pg/mL to 64.2 ± 17.7 pg/mL) (p = 0.00807). Additionally, there were significant differences in testosterone change between men with HbA1c improvements ≥1% (351.6 ± 123.9 ng/dL to 394.4 ± 136.5 ng/dL) compared to men with HbA1c changes <1% (331.8 ± 128.6 ng/dL to 316.1 ± 126.2 ng/dL) (p = 0.0413). CONCLUSION: GLP-1 RA therapy improves weight and HbA1c without adverse effects on testosterone. Those starting with lower testosterone values or attaining greater improvement in HbA1c may see additional benefits.

IMPACT OF STRUCTURED INSULIN ORDER SETS ON INPATIENT HYPOGLYCEMIA AND GLYCEMIC CONTROL.

Objective: In hospitalized patients, glycemic excursions outside recommended glycemic targets have been associated with increased morbidity and mortality. Despite recommendations to avoid use of correctional insulin alone for managing hyperglycemia, this approach remains common. We performed a quality improvement project aimed at both reducing hypoglycemic events and promoting increased use of basal insulin by updating our insulin order sets to reflect clinical practice guideline recommendations. Methods: Brooke Army Medical Center correctional insulin order sets were modified to reflect higher treatment thresholds and targets, and a basal insulin order was added with a recommended weight-based starting dose. Pre- and postintervention analyses were performed. Patients were included if they were prescribed subcutaneous insulin during their hospital stay. The following outcomes were measured: (1) glucose levels, and (2) prescriptions for basal insulin. Results: A significant reduction in hypoglycemia events was noted following the intervention (glucose <70 mg/dL: 9.2% pre-intervention vs. 8.8% postintervention; glucose <55 mg/dL: 4.2% pre-intervention vs. 2.2% postintervention). When excluding patients that were ordered correctional insulin alone but did not receive a dose, an increase in basal insulin use was seen (50% pre-intervention vs. 61% postintervention). Rates and severity of hyperglycemia (glucose >180 mg/dL) remained unchanged. Conclusion: The alteration in insulin order set parameters resulted in a significant reduction in hypoglycemia without significant increases in hyperglycemia. Although basal insulin use increased, optimal dosing recommendations were not often utilized. Further interventions are necessary to reduce hyperglycemia. Abbreviations: CPOE = computerized provider order entry; EMR = electronic medical record; HbA1c = hemoglobin A1c; LOS = length of stay; QI = quality improvement; SSI = sliding scale insulin.

Modeling Ertapenem: the impact of body mass index on distribution of the antibiotic in the body.

Ertapenem is an antibiotic commonly used to treat a broad spectrum of infections and is part of a broader class of antibiotics called carbapenems. Unlike other carbapenems, ertapenem has a longer half-life and thus only has to be administered once a day. Previously, a physiologically-based pharmacokinetic (PBPK) model was developed to investigate the uptake, distribution, and elimination of ertapenem following a single one gram dose in normal height, normal weight males. Due to the absorption properties of ertapenem, the amount of fat in the body can influence how the drug binds, how quickly the drug passes through the body, and thus how effective the drug might be. Thus, we have revised the model so that it is applicable to males and females of differing body mass index (BMI). Simulations were performed to consider the distribution of the antibiotic in males and females with varying body mass indexes. These results could help to determine if there is a need for altered dosing regimens in the future.

A physiologically-based pharmacokinetic model for the antibiotic ertapenem.

Ertapenem is an antibiotic commonly used to treat a broad spectrum of infections, which is part of a broader class of antibiotics called carbapenem. Unlike other carbapenems, ertapenem has a longer half-life and thus only has to be administered once a day. A physiologically-based pharmacokinetic (PBPK) model was developed to investigate the uptake, distribution, and elimination of ertapenem following a single one gram dose. PBPK modeling incorporates known physiological parameters such as body weight, organ volumes, and blood flow rates in particular tissues. Furthermore, ertapenem is highly bound in human blood plasma; therefore, nonlinear binding is incorporated in the model since only the free portion of the drug can saturate tissues and, hence, is the only portion of the drug considered to be medicinally effective. Parameters in the model were estimated using a least squares inverse problem formulation with published data for blood concentrations of ertapenem for normal height, normal weight males. Finally, an uncertainty analysis of the parameter estimation and model predictions is presented.