Subclinical Thyroid Dysfunction and the Risk of Cognitive Decline: a Meta-Analysis of Prospective Cohort Studies.

Although both overt hyper- and hypothyroidism are known to lead to cognitive impairment, data on the association between subclinical thyroid dysfunction and cognitive function are conflicting. This study sought to determine the risk of dementia and cognitive decline associated with subclinical thyroid dysfunction among prospective cohorts. We searched in MEDLINE and EMBASE from inception until November 2014. Two physicians identified prospective cohorts that assessed thyroid function and cognitive outcomes (dementia; Mini-Mental State Examination [MMSE]). Data were extracted by one reviewer following standardized protocols and verified by a second reviewer. The primary outcome was dementia and decline in cognitive function was the secondary outcome. Eleven prospective cohorts followed 16,805 participants during a median followup of 44.4 months. Five studies analyzed the risk of dementia in subclinical hyperthyroidism (SHyper) (n = 6410), six in subclinical hypothyroidism (SHypo) (n = 7401). Five studies analyzed MMSE decline in SHyper (n = 7895), seven in SHypo (n = 8960). In random-effects models, the pooled adjusted risk ratio for dementia in SHyper was 1.67 (95% confidence interval, 1.04; 2.69) and 1.14 (95% confidence interval, 0.84; 1.55) in SHypo vs euthyroidism, both without evidence of significant heterogeneity (I(2) = 0.0%). The pooled mean MMSE decline from baseline to followup (mean 32 mo) did not significantly differ between SHyper or SHypo vs euthyroidism. SHyper might be associated with an elevated risk for dementia, whereas SHypo is not, and both conditions are not associated with faster decline in MMSE over time. Available data are limited, and additional large, high-quality studies are needed

Novel bleeding risk score for patients with atrial fibrillation on oral anticoagulants, including direct oral anticoagulants

Objective: Balancing bleeding risk and stroke risk in patients with atrial fibrillation (AF) is a common challenge. Though several bleeding risk scores exist, most have not included patients on direct oral anticoagulants (DOACs). We aimed at developing a novel bleeding risk score for patients with AF on oral anticoagulants (OAC) including both vitamin K antagonists (VKA) and DOACs. Methods: We included patients with AF on OACs from a prospective multicenter cohort study in Switzerland (SWISS-AF). The outcome was time to first bleeding. Bleeding events were defined as major or clinically relevant non-major bleeding. We used backward elimination to identify bleeding risk variables. We derived the score using a point score system based on the β-coefficients from the multivariable model. We used the Brier score for model calibration (<0.25 indicating good calibration), and Harrel's c-statistics for model discrimination. Results: We included 2147 patients with AF on OAC (72.5% male, mean age 73.4 ± 8.2 years), of whom 1209 (56.3%) took DOACs. After a follow-up of 4.4 years, a total of 255 (11.9%) bleeding events occurred. After backward elimination, age > 75 years, history of cancer, prior major hemorrhage, and arterial hypertension remained in the final prediction model. The Brier score was 0.23 (95% confidence interval [CI] 0.19–0.27), the c-statistic at 12 months was 0.71 (95% CI 0.63–0.80). Conclusion: In this prospective cohort study of AF patients and predominantly DOAC users, we successfully derived a bleeding risk prediction model with good calibration and discrimination

Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts

Background Subclinical hyperthyroidism (SHyper) has been associated with increased risk of hip and other fractures, but the linking mechanisms remain unclear. Objective To investigate the association between subclinical thyroid dysfunction and bone loss. Methods Individual participant data analysis was performed after a systematic literature search in MEDLINE/EMBASE (1946–2016). Two reviewers independently screened and selected prospective cohorts providing baseline thyroid status and serial bone mineral density (BMD) measurements. We classified thyroid status as euthyroidism (thyroid-stimulating hormone [TSH] 0.45–4.49 mIU/L), SHyper (TSH < 0.45 mIU/L) and subclinical hypothyroidism (SHypo, TSH ≥ 4.50–19.99 mIU/L) both with normal free thyroxine levels. Our primary outcome was annualized percentage BMD change (%ΔBMD) from serial dual X-ray absorptiometry scans of the femoral neck, total hip and lumbar spine, obtained from multivariable regression in a random-effects two-step approach. Results Amongst 5458 individuals (median age 72 years, 49.1% women) from six prospective cohorts, 451 (8.3%) had SHypo and 284 (5.2%) had SHyper. During 36 569 person-years of follow-up, those with SHyper had a greater annual bone loss at the femoral neck versus euthyroidism: %ΔBMD = −0.18 (95% CI: −0.34, −0.02; I2 = 0%), with a nonstatistically significant pattern at the total hip: %ΔBMD = −0.14 (95% CI: −0.38, 0.10; I2 = 53%), but not at the lumbar spine: %ΔBMD = 0.03 (95% CI: −0.30, 0.36; I2 = 25%); especially participants with TSH < 0.10 mIU/L showed an increased bone loss in the femoral neck (%Δ BMD = −0.59; [95% CI: −0.99, −0.19]) and total hip region (%ΔBMD = −0.46 [95% CI: −1.05, −0.13]). In contrast, SHypo was not associated with bone loss at any site. Conclusion Amongst adults, SHyper was associated with increased femoral neck bone loss, potentially contributing to the increased fracture risk

Reliability comparison of various nuclear propulsion configurations for Mars mission

Currently, trade-offs are being made among the various propulsion systems being considered for the Space Exploration Initiative (SEI) missions. It is necessary to investigate the reliability aspects as well as the efficiency, mass savings, and experience characteristics of the various configurations. Reliability is a very important factor for the SEI missions because of the long duration and because problems will be fixed onboard. The propulsion options that were reviewed consist of nuclear thermal propulsion (NTP), nuclear electric propulsion (NEP) and various configurations of each system. There were four configurations developed for comparison with the NTP as baselined in the Synthesis (1991): (1) NEP, (2) hybrid NEP/NTP, (3) hybrid with power beaming, and (4) NTP upper stage on the heavy lift launch vehicle (HLLV). The comparisons were based more or less on a qualitative review of complexity, stress levels and operations for each of the four configurations. Each configuration included a pressurized NEP and an NTP ascent stage propulsion system for the Mars mission

Mars mission performance enhancement with hybrid nuclear propulsion

Nuclear electric propulsion (NEP), compared with chemical and nuclear thermal propulsion (NTP), can effectively deliver the same mass to Mars using much less propellant, consequently requiring less mass delivered to Earth orbit. The lower thrust of NEP requires a spiral trajectory near planetary bodies, which significantly increases the travel time. Although the total travel time is long, the portion of the flight time spent during interplanetary transfer is shorter, because the vehicle is thrusting for much longer periods of time. This has led to the supposition that NEP, although very attractive for cargo missions, is not suitable for piloted missions to Mars. However, with the application of a hybrid application of a hybrid approach to propulsion, the benefits of NEP can be utilized while drastically reducing the overall travel time required. Development of a dual-mode system, which utilizes high-thrust NTP to propel the spacecraft from the planetary gravitational influence and low-thrust NEP to accelerate in interplanetary space, eliminates the spiral trajectory and results in a much faster transit time than could be obtained by either NEP or NTP alone. This results in a mission profile with a lower initial mass in low Earth orbit. In addition, the propulsion system would have the capability to provide electrical power for mission applications

Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts

BACKGROUND: Subclinical hyperthyroidism (SHyper) has been associated with increased risk of hip and other fractures, but the linking mechanisms remain unclear. OBJECTIVE: To investigate the association between subclinical thyroid dysfunction and bone loss. METHODS: Individual participant data analysis was performed after a systematic literature search in MEDLINE/EMBASE (1946-2016). Two reviewers independently screened and selected prospective cohorts providing baseline thyroid status and serial bone mineral density (BMD) measurements. We classified thyroid status as euthyroidism (thyroid-stimulating hormone [TSH] 0.45-4.49 mIU/L), SHyper (TSH < 0.45 mIU/L) and subclinical hypothyroidism (SHypo, TSH ≥ 4.50-19.99 mIU/L) both with normal free thyroxine levels. Our primary outcome was annualized percentage BMD change (%ΔBMD) from serial dual X-ray absorptiometry scans of the femoral neck, total hip and lumbar spine, obtained from multivariable regression in a random-effects two-step approach. RESULTS: Amongst 5458 individuals (median age 72 years, 49.1% women) from six prospective cohorts, 451 (8.3%) had SHypo and 284 (5.2%) had SHyper. During 36 569 person-years of follow-up, those with SHyper had a greater annual bone loss at the femoral neck versus euthyroidism: %ΔBMD = -0.18 (95% CI: -0.34, -0.02; I2 = 0%), with a nonstatistically significant pattern at the total hip: %ΔBMD = -0.14 (95% CI: -0.38, 0.10; I2 = 53%), but not at the lumbar spine: %ΔBMD = 0.03 (95% CI: -0.30, 0.36; I2 = 25%); especially participants with TSH < 0.10 mIU/L showed an increased bone loss in the femoral neck (%Δ BMD = -0.59; [95% CI: -0.99, -0.19]) and total hip region (%ΔBMD = -0.46 [95% CI: -1.05, -0.13]). In contrast, SHypo was not associated with bone loss at any site. CONCLUSION: Amongst adults, SHyper was associated with increased femoral neck bone loss, potentially contributing to the increased fracture risk

THYROID DYSFUNCTION AND THE RISK OF DEMENTIA AND COGNITIVE DECLINE: SYSTEMATIC REVIEW, META-ANALYSIS AND CLINICAL IMPLICATIONS

Pathophysiology, epidemiology and therapy of agein