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.
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.
Objectives
In 2018, a nationwide mandatory switch from originator to biosimilar
adalimumab was conducted in Denmark. The available biosimilar was GP2017
(Hyrimoz) in Eastern regions and SB5 (Imraldi) in Western regions. We
aimed to assess the comparative effectiveness of GP2017 versus SB5 in
patients with rheumatoid arthritis (RA)/psoriatic arthritis (PsA)/axial
spondyloarthritis (AxSpA).
Methods
Observational cohort study based on the DANBIO registry with
geographical cluster pseudo-randomisation, analysed by emulating a
randomised clinical trial. Main outcome was adjusted 1-year treatment
retention (Cox regression). Furthermore, 6 months’ remission rates
(logistic regression), reasons for withdrawal and back-switching to
originator were investigated (overall and stratified by
indication).
Results
Overall, of 1570 eligible patients, 1318 switched and were included
(467 RA/321 PsA/530 AxSpA); 623 (47%) switched to GP2017, 695 (53%) to
SB5. Baseline characteristics of the two clusters were largely similar,
but some differences in registration practice were observed. The
combined 1-year retention rate for the two biosimilars was 89.5%.
Compared with SB5, estimated risk of withdrawal for GP2017 was lower (HR
0.60; 95% CI 0.42 to 0.86) and 6 months’ remission rate was higher (OR
1.72; 95% CI 1.25 to 2.37). Stratified analyses gave similar results
(statistically significant for RA). During 1 year, 8.5% and 12.9%
withdrew GP2017 and SB5, respectively (primarily lack of effect and
adverse events), of whom 48 patients (3.6%) back-switched.
Conclusion
This head-to-head comparison of GP2017 versus SB5 following a
mandatory switch from the originator indicated differences in
effectiveness in routine care. This may reflect a true difference, but
other explanations, for example, differences in excipients, differences
between clusters and residual confounding cannot be ruled out.
Levothyroxine treatment in patients with subclinical hypothyroidism and heart disease was not associated with a significant benefit nor risk of all-cause mortality, MACE, or hospital admission in this large real-world cohort study.
Of a random sample comprising 4581 subjects from The Copenhagen County, 3608 (79%) attended an interview and a general health examination. The subjects were defined as suffering from subjective postphlebitic syndrome if they claimed of lower extremity pain or cramps at rest and from objective postphlebitic syndrome if varicose veins, edema, lower extremity ulcers, or skin changes were present. By means of logistic regression analysis, subjective postphlebitic syndrome was found independently associated with previous thromboembolism, obesity, increasing age, female sex, hormonal therapy, varicose veins, and previous major abdominal surgery. Objective postphlebitic syndrome was associated with previous thromboembolism, obesity, former birthgiving, and high social status. The findings support the view that subclinical deep venous thrombosis in connection with previous surgery may give rise to symptoms in the lower extremities.
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