13 research outputs found

    John Hick's paraeschatology

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    Suicide and Self-starvation

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    Levothyroxine Treatment and Cardiovascular Outcomes in Older People With Subclinical Hypothyroidism: Pooled Individual Results of Two Randomised Controlled Trials.

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    Background The cardiovascular effects of treating older adults with subclinical hypothyroidism (SCH) are uncertain. Although concerns have been raised regarding a potential increase in cardiovascular side effects from thyroid hormone replacement, undertreatment may also increase the risk of cardiovascular events, especially for patients with cardiovascular disease (CVD). Objective To determine the effects of levothyroxine treatment on cardiovascular outcomes in older adults with SCH. Methods Combined data of two parallel randomised double-blind placebo-controlled trials TRUST (Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism - a randomised placebo controlled Trial) and IEMO80+ (the Institute for Evidence-Based Medicine in Old Age 80-plus thyroid trial) were analysed as one-stage individual participant data. Participants aged ≥65 years for TRUST (n=737) and ≥80 years for IEMO80+ (n=105) with SCH, defined by elevated TSH with fT4 within the reference range, were included. Participants were randomly assigned to receive placebo or levothyroxine, with titration of the dose until TSH level was within the reference range. Cardiovascular events and cardiovascular side effects of overtreatment (new-onset atrial fibrillation and heart failure) were investigated, including stratified analyses according to CVD history and age. Results The median [IQR] age was 75.0 [69.7-81.1] years, and 448 participants (53.2%) were women. The mean TSH was 6.38± SD 5.7 mIU/L at baseline and decreased at 1 year to 5.66 ± 3.3 mIU/L in the placebo group, compared with 3.66 ± 2.1 mIU/L in the levothyroxine group (p<0.001), at a median dose of 50 μg. Levothyroxine did not significantly change the risk of any of the prespecified cardiovascular outcomes, including cardiovascular events (HR 0.74 [0.41-1.25]), atrial fibrillation (HR 0.69 [0.32-1.52]), or heart failure (0.41 [0.13-1.35]), or all-cause mortality (HR 1.28 [0.54-3.03]), irrespective of history of CVD and age. Conclusion Treatment with levothyroxine did not significantly change the risk of cardiovascular outcomes in older adults with subclinical hypothyroidism, irrespective of a history of cardiovascular disease and age. Clinical Trial Registration [ClinicalTrials.gov], identifier [NCT01660126] (TRUST); Netherlands Trial Register: NTR3851 (IEMO80+)

    Missingness matters: a secondary analysis of thromboelastography measurements from a recent prehospital randomized tranexamic acid clinical trial

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    Background Tranexamic acid (TXA) has been hypothesized to mitigate coagulopathy in patients after traumatic injury. Despite previous prehospital clinical trials demonstrating a TXA survival benefit, none have demonstrated correlated changes in thromboelastography (TEG) parameters. We sought to analyze if missing TEG data contributed to this paucity of findings.Methods We performed a secondary analysis of the Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport Trial. We compared patients that received TEG (YES-TEG) and patients unable to be sampled (NO-TEG) to analyze subgroups in which to investigate TEG differences. TEG parameter differences across TXA intervention arms were assessed within subgroups disproportionately present in the NO-TEG relative to the YES-TEG cohort. Generalized linear models controlling for potential confounders were applied to findings with p&lt;0.10 on univariate analysis.Results NO-TEG patients had lower prehospital systolic blood pressure (SBP) (100 (78, 140) vs 125 (88, 147), p&lt;0.01), lower prehospital Glascow Coma Score (14 (3, 15) vs 15 (12, 15), p&lt;0.01), greater rates of prehospital intubation (39.4% vs 24.4%, p&lt;0.01) and greater mortality at 30 days (36.4% vs 6.8%, p&lt;0.01). NO-TEG patients had a greater international normalized ratio relative to the YES-TEG subgroup (1.2 (1.1, 1.5) vs 1.1 (1.0, 1.2), p=0.04). Within a severe prehospital shock cohort (SBP&lt;70), TXA was associated with a significant decrease in clot lysis at 30 min on multivariate analysis (β=−27.6, 95% CI (−51.3 to –3.9), p=0.02).Conclusions Missing data, due to the logistical challenges of sampling certain severely injured patients, may be associated with a lack of TEG parameter changes on TXA administration in the primary analysis. Previous demonstration of TXA’s survival benefit in patients with severe prehospital shock in tandem with the current findings supports the notion that TXA acts at least partially by improving clot integrity.Level of evidence Level II
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