Levothyroxine Dosing in Older Adults: Recommendations Derived From The Baltimore Longitudinal Study of Aging.

OBJECTIVE: As thyroid hormone metabolism slows with advancing age, treatment dosing requirements change. Guidelines recommend titration from a low starting dose for older adults with hypothyroidism while providing weight-based estimates for younger populations. However, rapid replacement may be appropriate with acute onset of overt hypothyroidism. Therefore, a weight-based recommendation specific to older adults is needed. METHODS: We determined mean levothyroxine dose using actual and ideal body weight (IBW) ratios for the outcome of euthyroid on therapy relative to assay-specific and proposed age-specific ranges for independently living participants aged ≥65 years in the Baltimore Longitudinal Study of Aging. We examined risk factors to identify those at highest risk of overtreatment using regression analyses adjusted for potential covariables and clustering to account for multiple visits per individual. RESULTS: One hundred eighty-five participants aged ≥65 years were on levothyroxine at 645 eligible visits. At euthyroid visits, participants were on an average dose of 1.09 µg/kg (1.35 µg/kg IBW), with 84% of euthyroid individuals on a dose of <1.6 µg/kg. Average euthyroid dose did not differ by sex using either actual body weight (ABW) or IBW. For obese individuals, mean euthyroid dose was lower if calculated using ABW (0.9 µg/kg vs 1.14 µg/kg; P < .01) but similar if calculated using IBW (1.42 vs 1.32 µg/kg IBW; P = .41) compared with those with a body mass index of <30. CONCLUSION: Thyroid hormone dose per body weight estimates for replacement in older adults (1.09 µg/kg ABW or 1.35 µg/kg IBW) are one-third lower than current weight-based dose recommendations for younger populations.

Free Thyroxine Distinguishes Subclinical Hypothyroidism From Other Aging-Related Changes in Those With Isolated Elevated Thyrotropin.

Background: Although a finding of isolated elevated thyrotropin (TSH) often leads to treatment with thyroid hormone, it is not specific to a diagnosis of subclinical hypothyroidism, particularly in older adults. We have previously used longitudinal assessment of TSH and free thyroxine (FT4) to distinguish primary and secondary changes in the hypothalamic-pituitary-thyroid (HPT) axis, an approach which is impractical for clinical diagnosis. Objective: Identify contemporaneous clinical tests and criteria that predict the longitudinally-derived HPT axis phenotype in those with isolated elevated TSH. Methods: Using data from Baltimore Longitudinal Study of Aging, participants with over three years of follow up not on thyroid hormone replacement, with a TSH above the reference range and an in-range FT4 at the current visit, and at least 1% per year increase in TSH (mean 6.9% annual increase; n=72), we examined correlations between various clinical factors and the change in FT4 across the phenotypic range from emerging hypothyroidism, with falling FT4, to adaptive stress-response, with rising FT4. Results: Current FT4 level, but not TSH, Free T3, anti-TPO antibody status, age or sex, was significantly associated with phenotype, determined by the annual rate of change in FT4 in those with elevated and rising TSH, both as a continuous variable (ß=0.07 per ng/dL increase in FT4; p<0.001) and in quartiles (p<0.001). We estimated a threshold for FT4 of less than 0.89 ng/dL (11.45 pmol/L; the 24th percentile of the reference range), as predictive of a phenotype in the first quartile, consistent with subclinical hypothyroidism, while a FT3:FT4 ratio below 2.77 predicted a phenotype in the fourth quartile, more consistent with adaptive stress-response. Conclusions: In those with isolated elevated TSH, a FT4 in the lowest quartile of the reference range differentiates those with developing hypothyroidism from other HPT-axis aging changes.

The Global Health Security Index is not predictive of vaccine rollout responses among OECD countries.

OBJECTIVE: This study sought to evaluate the utility of the Global Health Security (GHS) index in predicting the launch of COVID-19 vaccine rollout by Organization for Economic Cooperation and Development (OECD) member countries. METHODS: Country-level data on the preparedness to respond to infectious disease threats through vaccination rollout were collected using the GHS index. OECD member countries were rank-ordered based on the percentage of their populations fully vaccinated against COVID-19. Rank-ordering was conducted from the lowest to the highest, with each country assigned a score ranging from 1 to 33. Spearman's rank correlation between the GHS index and the percentage of the population that is fully vaccinated was also performed. RESULTS: Israel, ranked 34th in the world on the GHS index for pandemic preparedness, had the highest percentage of the population that was fully vaccinated against COVID-19 within 2 months of the global vaccine rollout. The Spearman rank correlation coefficient between GHS index and the percentage of population fully vaccinated was -0.1378, with a p-value of 0.43. CONCLUSION: The findings suggest an absence of correlation between the GHS index rating and the COVID-19 vaccine rollout of OECD countries, indicating that the preparedness of OECD countries for infectious disease threats may not be accurately reflected by the GHS index.

Statins use and COVID-19 outcomes in hospitalized patients.

BACKGROUND: There is an urgent need for novel therapeutic strategies for reversing COVID-19-related lung inflammation. Recent evidence has demonstrated that the cholesterol-lowering agents, statins, are associated with reduced mortality in patients with various respiratory infections. We sought to investigate the relationship between statin use and COVID-19 disease severity in hospitalized patients. METHODS: A retrospective analysis of COVID-19 patients admitted to the Johns Hopkins Medical Institutions between March 1, 2020 and June 30, 2020 was performed. The outcomes of interest were mortality and severe COVID-19 infection, as defined by prolonged hospital stay (≥ 7 days) and/ or invasive mechanical ventilation. Logistic regression, Cox proportional hazards regression and propensity score matching were used to obtain both univariable and multivariable associations between covariates and outcomes in addition to the average treatment effect of statin use. RESULTS: Of the 4,447 patients who met our inclusion criteria, 594 (13.4%) patients were exposed to statins on admission, of which 340 (57.2%) were male. The mean age was higher in statin users compared to non-users [64.9 ± 13.4 vs. 45.5 ± 16.6 years, p <0.001]. The average treatment effect of statin use on COVID-19-related mortality was RR = 1.00 (95% CI: 0.99-1.01, p = 0.928), while its effect on severe COVID-19 infection was RR = 1.18 (95% CI: 1.11-1.27, p <0.001). CONCLUSION: Statin use was not associated with altered mortality, but with an 18% increased risk of severe COVID-19 infection.

Male Sex Is Associated With Worse Microbiological and Clinical Outcomes Following Tuberculosis Treatment: A Retrospective Cohort Study, a Systematic Review of the Literature, and Meta-analysis.

BACKGROUND: Although the incidence of tuberculosis is higher in men than in women, the relationship of sex with tuberculosis treatment outcomes has not been adequately studied. METHODS: We performed a retrospective cohort study and a systematic review and meta-analysis of observational studies during the last 10 years to assess sex differences in clinical and microbiological outcomes in tuberculosis. RESULTS: In our cohort of 2894 Taiwanese patients with drug-susceptible pulmonary tuberculosis (1975 male and 919 female), male patients had higher adjusted hazards of 9-month mortality due to all causes (hazard ratio, 1.43 [95% confidence interval (CI), 1.03-1.98]) and infections (1.70 [1.09-2.64]) and higher adjusted odds of 2-month sputum culture positivity (odds ratio [OR], 1.56 [95% CI, 1.05-2.33]) compared with female patients. Smear positivity at 2 months did not differ significantly (OR, 1.27 [95% CI, .71-2.27]) between the sexes. Among 7896 articles retrieved, 398 were included in our systematic review describing a total of 3 957 216 patients. The odds of all-cause mortality were higher in men than in women in the pooled unadjusted (OR, 1.26 [95% CI, 1.19-1.34]) and adjusted (1.31 [1.18-1.45]) analyses. Men had higher pooled odds of sputum culture (OR, 1.44 [95% CI, 1.14-1.81]) and sputum smear (1.58 [1.41-1.77]) positivity, both at the end of the intensive phase and on completion of treatment. CONCLUSIONS: Our retrospective cohort showed that male patients with tuberculosis have higher 9-month all-cause and infection-related mortality, with higher 2-month sputum culture positivity after adjustment for confounding factors. In our meta-analysis, male patients showed higher all-cause and tuberculosis-related mortality and higher sputum culture and smear positivity rates during and after tuberculosis treatment.

Thyroid Hormone Supplementation and All-Cause Mortality in Community-Dwelling Older Adults: Results from the Baltimore Longitudinal Study of Aging.

BACKGROUND: Although elevated thyrotropin (TSH) is common in older adults, controversy exists over what degree of elevation should be treated with thyroid hormone supplements. Isolated, elevated TSH in this population can be consistent with aging-related adaptations rather than indicative of primary thyroid disease, raising the possibility that thyroid hormone replacement may be harmful. OBJECTIVES: Determine the association between all-cause mortality and levothyroxine use among older adults. DESIGN: Longitudinal observational study. SETTING: Baltimore Longitudinal Study of Aging. PARTICIPANTS: One thousand two hundred and fifty eight community dwelling adult participants aged 65+ with an average of 9 years of follow up. MEASUREMENTS: Thyroid and pituitary hormone levels and thyroid hormone supplementation were determined at each visit. Incident rate ratios (IRR) for all-cause mortality were calculated using time-dependent Poisson regression models to accommodate the varying start times. To isolate the effects of hormone replacement from its effects on TSH, the association between treatment and all-cause mortality was analyzed in participants with stable thyroid function status throughout follow-up (N = 638). RESULTS: Thyroid hormone supplementation was not associated with a significant increase all-cause mortality in the subsequent year in the fully adjusted model (IRR = 1.40, 95% confidence interval (CI) = 0.93-2.12). In a stratified analysis of euthyroid participants, thyroid hormone use was associated with significantly greater mortality, with an adjusted IRR = 1.81 (95% CI = 1.10-2.98). CONCLUSION: The increased mortality associated with thyroid hormone use among the subclass of euthyroid community dwelling older adults is consistent with a model in which TSH elevation can result from a variety of underlying pathophysiologic processes, not all of which should be treated with thyroid hormone supplementation. Clinicians should consider overall clinical status when interpreting an isolated elevated TSH in older adults.

Comparative Effectiveness of Roux-en Y Gastric Bypass Versus Vertical Sleeve Gastrectomy for Sustained Remission of Type 2 Diabetes Mellitus.

BACKGROUND: Bariatric surgery results in rapid weight loss and resolution of comorbidities such as type 2 diabetes mellitus (T2DM). We aimed to determine whether the type of surgical procedure-vertical sleeve gastrectomy (VSG) versus Roux-en-Y gastric bypass (RYGB)-was associated with sustained remission from T2DM, and to identify other independent predictors of sustained remission. METHODS: Using the IBM MarketScan database of privately insured patients in the United States, we performed a retrospective cohort study on individuals aged 18-65 y with T2DM on hypoglycemic medication, who underwent either VSG or RYGB from 2010 to 2016. Remission was defined as no refill of antidiabetic medication 180 d after a patient's medication was expected to run out and recurrence as medication refill after at least 180 d of remission. RESULTS: Of 5119 patients in our cohort, 4127 (81%) experienced remission of T2DM, and 816 (19.8%) of the 4127 patients experienced recurrence. Patients who underwent RYGB had a 24% (HR = 1.24, 95% CI: 1.16, 1.32) increased probability of achieving remission compared with VSG. RYGB had a 36% (HR = 0.64, 95% CI: 0.55, 0.74) decreased risk of recurrence compared with VSG. A higher number of diabetic medications at the time of surgery and a higher Charlson index score were associated with decreased probability of remission and an increased risk of recurrence of T2DM. CONCLUSIONS: While both procedures are initially effective, RYGB may be better than VSG at providing lasting remission of T2DM.

The Global Health Security Index is not predictive of coronavirus pandemic responses among Organization for Economic Cooperation and Development countries.

The ongoing COVID-19 pandemic has devastated many countries with ripple effects felt in various sectors of the global economy. In November 2019, the Global Health Security (GHS) Index was released as the first detailed assessment and benchmarking of 195 countries to prevent, detect, and respond to infectious disease threats. This paper presents the first comparison of Organization for Economic Cooperation and Development OECD countries' performance during the pandemic, with the pre-COVID-19 pandemic preparedness as determined by the GHS Index. Using a rank-based analysis, four indices were compared between select countries, including total cases, total deaths, recovery rate, and total tests performed, all standardized for comparison. Our findings suggest a discrepancy between the GHS index rating and the actual performance of countries during this pandemic, with an overestimation of the preparedness of some countries scoring highly on the GHS index and underestimation of the preparedness of other countries with relatively lower scores on the GHS index.