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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.

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.

To investigate the association of the two most common bariatric surgical procedures, vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB), with sustained remission from chronic migraine. Using IBM MarketScan® research database to examine inpatient and pharmacy claims from 2010 through 2017. A cohort of bariatric patients with chronic migraine was created using inclusion and exclusion criteria. Remission was defined as no refill of first-line migraine medication for 180 days after a patients’ medication was expected to run out, and recurrence as medication refill after at least 180 days of remission. Of 1680 patients in our cohort, 931 (55.4%) experienced remission of migraine. Of these, 462 (49.6%) had undergone VSG, while 469 (50.4%) had undergone RYGB. Patients who underwent RYGB had an 11% (RR = 1.11, 95% CI: 1.05, 1.17) increase in likelihood of remission of migraine and a 20% (RR = 0.80, 95% CI: 0.63, 1.04) decrease in likelihood of recurrence of migraine compared to patients who underwent VSG. Older age group, higher number of medications at time of surgery, and female sex were associated with a decreased likelihood of remission. Type of bariatric procedure, age, number of medications at surgery, and sex were the most important predictors of migraine remission after surgery.

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.

BackgroundAlthough 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.ObjectiveIdentify contemporaneous clinical tests and criteria that predict the longitudinally-derived HPT axis phenotype in those with isolated elevated TSH.MethodsUsing 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.ResultsCurrent 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 (β=0.07 per ng/dL increase in FT4; pth 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.ConclusionsIn 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.

RationaleAlthough the incidence of tuberculosis (TB) is higher in males compared to females, the relationship of sex with TB treatment outcomes has not been adequately studied.Objectives and MethodsWe performed a retrospective cohort study and a systematic review and meta-analysis of observational studies during the last 10 years to assess the sex differences in clinical and microbiological outcomes in tuberculosis.Measurements and Main ResultsIn our cohort of 2,894 patients with drug-susceptible pulmonary TB (1,975 males and 919 females), males had higher adjusted hazards of mortality due to all causes (HR 1·43,95%CI 1.03-1.98) and infections (HR 1.70, 95%CI 1.09-2.64) at 9 months and higher adjusted odds ratio for sputum culture (OR 1.56,95%CI 1.05-2.33) and similar odds ratio for smear positivity (OR 1.27, 0.71-2.27) at 2 months compared to females. Among 7896 articles retrieved, 398 articles were included in our systematic review with a total of 3,957,216 patients. The odds of all-cause mortality was higher in males compared to females in the pooled unadjusted (OR 1.26, 95%CI 1.19-1.34) and adjusted (OR 1.31, 95%CI 1.18-1.45) analyses. Relative to females, males had higher pooled odds of sputum culture (OR 1.44,95% CI 1.14-1.81) and sputum smear (OR 1.58,95%CI 1.41-1.77) positivity at the end of the intensive phase, and upon completion of treatment.ConclusionsDuring TB treatment, males have higher all-cause-, infection- and TB-related mortality, as well as higher rates of sputum smear and culture positivity, both after the intensive phase and at the completion of TB treatment, after adjusting for confounding factors.

Background: Given the relatively modest benefit of currently available treatments in improving COVID-19 clinical outcomes, there is an urgent need for novel therapeutic strategies, especially in reversing associated lung inflammation. Attention has focused on repurposing existing agents with immune modulatory properties to accelerate their incorporation into clinical practice. Recent evidence has demonstrated that the cholesterol-lowering agents, statins, are associated with reduced mortality in patients with influenza, sepsis, community-acquired pneumonia, and chronic obstructive pulmonary diseases (COPD). 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

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.

Abstract: Introduction: Thyrotropin (TSH) levels on average are higher and vary more widely among older adults.1 Large meta-analyses and treatment trials for isolated elevated TSH in older adults did not demonstrate harm from no treatment or benefit from treatment in this population.2 Isolated, elevated TSH can result from adaptations to aging, rather than primary thyroid disease, suggesting that thyroid hormone treatment could actually cause harm.3 Objective:To determine if there is a survival effect from thyroid hormone treatment in adults aged 65+. Methodology:Thyroid functional status and thyroid hormone exposure were analyzed for 1,258 participants of the BLSA aged 65+ through death or end of follow up. We analyzed exposures by visit and also compared survival between individuals with consistently elevated, euthyroid or low TSH both on and off of therapy.Incident rate ratios (IRR) were calculated using time-dependent Poisson regression models. Covariates included age, sex, race, walking index (measure of physical function), self-rated health (SF-12), body mass index (BMI), smoking and comorbidity score. Results: Average follow-up was 9 years, with 169 deaths over the study period. The cohort comprised 49.5% women, with average age in the study being 78 years (SD ±8.2). Thyroid hormone use trended towards harm analyzed at each visit with an IRR=1.40 (95% CI 0.93–2.12) after adjusting for other covariates. Among ‘treated-to-target’versus euthyroid individuals, thyroid hormone use was associated with a significantly increased mortality rate with an IRR=1.80 (95% CI 1.09–2.96) in multivariable analysis. Conclusion: Thyroid hormone replacement among older adults,even when treated-to-target, is associated with a significantly increased mortality risk compared to euthyroid individuals with no history of thyroid hormone exposure. This suggests that treating isolated elevated TSH when changes are aging adaptations rather than primary thyroid disease could adversely affect health by altering key homeostatic adaptation. We recommend clinicians consider the underlying physiology of aging and employ age specific reference ranges when deciding on treatment for elevated TSH in older adults.4References 1. Surks et al., J Clin Endo. Met. 2007;92(12):4575–4582. 2. Stott et al., NEJM. 2017;376(26):2534–2544. 3. Mammen et al., Thyroid. 2017;27(11):1370–1377. 4. Surks et al., J Clin Endo. Met. 2010:95(2):496-502Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

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.

BackgroundThere 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.MethodsA 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.ResultsOf 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 ConclusionStatin use was not associated with altered mortality, but with an 18% increased risk of severe COVID-19 infection.

Because of heterogeneity in hormonal aging,1 we believe isolated elevated TSH is insufficient to drive clinical decision making for thyroid hormone replacement in older adults. We performed a cross-sectional study involving 63 older adult participants of the BLSA in order to assess the diagnostic value of individual hormone levels or free T3: free T4 ratio for differentiating thyroid-aging phenotypes. We defined two phenotypic groups, central adaptation and primary hypothyroidism, both with a rising TSH and with a rising or falling FT4 respectively. Fifty-four percent of study participants were male, the average age was 78.8 years, and 66.7% had the primary hypothyroidism phenotype. The unadjusted odds ratio of having the central adaptation phenotype is 23.40 (95% CI 3.66-149.73) for every unit increase in the FT3:FT4 ratio. The ROC curve had a C-statistic of 0.815. Similarly, FT4 alone distinguished the phenotypes with a C-statistic of 0.864. In contrast, TSH and FT3 were not predictive (C-statistic of 0.617, and 0.479 respectively). When the analysis is limited to the 24 individuals with elevated TSH, the ratio remains predictive (0.839). Both the higher FT4 and the lower ratio found in individuals with adaptive changes are consistent with a physiology similar to the adaptations seen in acute illness. This supports the hypothesis that elevated TSH can represent a response to stressors with aging and doesn’t always warrant treatment with thyroid hormone. Our findings suggest that full thyroid function panel can be used to make better diagnostic decisions in older adults.