BackgroundSubclinical hypothyroidism is associated with a number of cardiovascular risk factors, yet only limited data exist on long-term outcome of levothyroxine treatment of this condition with respect to hard end-points. The aim of this retrospective cohort study was to determine effects of levothyroxine treatment on myocardial infarction (MI), cardiovascular death and all-cause mortality, in patients with subclinical hypothyroidism.Methods and ResultsPrimary care patients aged 18 years and older that underwent thyroid function tests between 2000 and 2009 were enrolled. Participants were identified by individual-level linkage of nationwide registers. Patients with subclinical hypothyroidism at baseline were included in the study. Exclusion criteria included a history of thyroid disease, related medication or medication affecting thyroid function. The total cohort comprised 628,953 patients of which 12,212 (1.9%) had subclinical hypothyroidism (mean age 55.2 [SD ± 18.8] years; 79.8% female). Within the first six months 2,483 (20.3%) patients claimed a prescription for levothyroxine. During a median follow-up of 5.0 (IQR: 5.2) years, 358 MI’s and 1,566 (12.8%) deaths were observed. Out of these, 766 of the deaths were cardiovascular related. No beneficial effects were found in levothyroxine treated patients on MI (IRR 1.08 [95% CI: 0.81 to 1.44]), cardiovascular death (IRR 1.02 [95% CI: 0.83 to 1.25]) or all-cause mortality (IRR 1.03 [95% CI: 0.90 to 1.19]), except in patients under the age of 65 years (IRR 0.63 [95% CI: 0.40 to 0.99]).ConclusionLevothyroxine substitution in subclinical hypothyroid patients does not indicate an association with lower mortality or decreased risk of MI.

Prolonged thromboprophylaxis had no significant effect on the incidence of DVT occurring late after general surgery.

Van der Waals energies of interaction between model cell surfaces are calculated for various distances of separation, layer thicknesses and compositions of cell surfaces and intercellular media. In these calculations the cell peripheries are considered to consist of two layers: (1) A phospholipid-cholesterol-protein plasma membrane and (2) a surface coat, which consists of protein, sugar and water. The required Van der Waals parameters of sugars, phospholipids and cholesterol are derived from refractive indices of their solutions in the visible and ultraviolet regions. Polarizabilities and Van der Waals parameters of these substances are determined and shown to be almost independent of concentration of solutions. Resulting isotropic polarizabilities differ by less than five percent from values obtained by the addition of bond polarizabilities. The magnitude of Van der Walls interactions between cell surfaces has been found to vary with composition according to the following sequence: water less than phospholipid less than cholesterol, protein less than sugar. A decrease in the concentration of a given substance in the cell surface at the expense of a corresponding increase in the concentration of a substance preceding it in this sequence lowers the magnitude of attractive interactions, whereas a similar change in the extracellular medium would have an opposite effect. A consideration of experimentally found variations in composition of cell surfaces results in calculated values of Hamaker's coefficients between 8 X 10(-15) ergs and 6 X 10(-14) ergs at 50 A distance of separation, which corresponds to free energies per unit area of 210-1600 kT/mu2.

Nearly one in five (19%) biologic treatments for RA was prescribed in Denmark as monotherapy, of which 70% were on monotherapy from bio-initiation and 30% were on monotherapy after cessation of a concomitant csDMARD. Acceptable drug adherence and remission rates were achieved with bDMARDs. With the exception of infliximab, no statistically significant differences were observed between anti-TNFs and biologics with other modes of action.