Pharmacokinetic profile of nomegestrol acetate and 17β-estradiol after multiple and single dosing in healthy women

BackgroundThe pharmacokinetics of the monophasic oral contraceptive nomegestrol acetate (NOMAC) plus 17β-estradiol (E₂) were investigated after a single dose and multiple dosing.Study designNOMAC/E₂ (2.5 mg/1.5 mg) was administered daily to healthy women (18–50 years, n= 23) for 24 days; blood samples for pharmacokinetic analysis were obtained on Day 24 and again, after a 10-day pill-free interval, on Day 35 after a single dose.ResultsNOMAC reached steady state after 5 days with mean ± standard deviation (SD) trough NOMAC concentration (C_av) of 4.4±1.4 ng/mL. On Day 24, mean±SD peak NOMAC concentration (C_max, 12.3±3.5 ng/mL) was reached in mean 1.5 h (t_max); the mean±SD elimination half-life (t_½) was 45.9±15.3 h. After a single dose, NOMAC mean±SD C_max was 7.2±2.0 ng/mL and mean±SD t_½ was 41.9±16.2 h. On Day 24, E₂ mean±SD C_av was 50.3±25.7 pg/mL; mean±SD C_max was 86.0±51.3 pg/mL. After a single dose, mean±SD E₂ C_max was 253±179 pg/mL.ConclusionsThese data demonstrate that NOMAC/E₂ has a pharmacokinetic profile consistent with once-daily dosing.     

Metatarsus adductus: Development of a non‐surgical treatment pathway

Metatarsus adductus (MA) occurs in one to two cases per 1000 births and is the most common congenital foot deformity in newborns. The appearance is that of a curved or adducted forefoot with a normal hindfoot. A systematic literature review was conducted to answer the following question: For a child who presents with MA, what is the most evidence‐based conservative treatment option? Thirteen articles were reviewed using the National Health and Medical Research Council levels of evidence and guidelines for clinical practice. Conservative treatment options reported on included the following: no treatment, stretching, splinting, serial casting, sitting and sleeping positions and footwear/orthotics. There was strong evidence supporting no treatment in the case of flexible MA. Some limited evidence was found for the treatment of semi‐rigid MA. Clinicians should use these recommendations together with clinical experience when advising parents on treatment of MA.     

Improvements in physical function and pain sustained for up to 10 years after knee or hip arthroplasty irrespective of mental health status before surgery

Background and purpose — There are concerns that mental health (MH) may influence outcomes of total knee arthroplasty (TKA) or total hip arthroplasty (THA). We examined effects of poor MH before surgery on long-term outcomes of osteoarthritis-related TKA or THA in women.

Patients and methods — The data were from 9,737 middle-aged participants (47–52 years) and 9,292 older participants (73–78 years) in the Australian Longitudinal Study on Women’s Health who completed surveys between 1998 and 2013. Dates of arthroplasties were obtained from the Australian Orthopaedics Association National Joint Replacement Registry. Participants without procedures were matched with participants with procedures. Trajectories of the Short-Form 36 scores for physical functioning, bodily pain, social functioning, and mental health based on mixed modeling were plotted for participants with and without surgery (stratified according to mental health, separately for TKA and THA, and for middle-aged and older participants).

Results — In middle-aged women with poor and good MH, TKA improved physical function and reduced bodily pain, with improvements sustained up to 10 years after surgery. TKA contributed to restoration of social function in women with good MH, but this was less clear in women with poor MH. In both MH groups, mental health appeared to be unaffected by TKA. Similar patterns were observed after THA, and in older women.

Interpretation — Recovery of physical and social function and reductions in pain were sustained for up to 10 years after surgery. Improvements in physical function and pain were also observed in women with poor mental health. Thus, in our view poor mental health should not be a contraindication for arthroplasty.