Objective: To examine whether vitamin D supplementation in patients with depression would result in a reduction in Hamilton D-17 depression score (primary outcome) at 3 and 6 months compared to controls and to explore the correlations between serum vitamin D and symptoms of depression, wellbeing, systolic blood pressure, and waist circumference. In this outpatient multicentre study conducted between 2010 and 2013, patients, 18–65 years old, diagnosed with mild to severe depression were randomly assigned to receive D supplementation 70 micrograms daily or placebo on top of standard treatment. Participants, care givers and those assessing the outcomes were blinded to group assignment. Results: At baseline, 23 patients had a normal 25(OH)D level, 22 had insufficiency (< 25 nmol/L), and 17 had deficiency (25–50 nmol/L). No significant reduction in depression was seen after vitamin D supplementation compared to placebo at Hamilton (18.4–18.0; p = 0.73 at 12 weeks). Vitamin D supplementation did not provide a reduction in symptom score among patients with depression. Trial registration The trial was registered in the National Board of Health (EudraCT: 2011-002585-20) and in ClinicalTrials.Gov (NCT01390662).

Context Large, longitudinal studies on androgen levels in pregnant women with polycystic ovary syndrome (PCOS) are lacking. While metformin has a mild androgen-lowering effect in non-pregnant women with PCOS, its effects on maternal androgen levels in pregnancy are less well understood. Objective To describe androgen patterns in pregnant women with PCOS and in healthy control women, and to explore the potential effects of metformin on maternal androgen levels in PCOS. Design and Setting A post hoc analysis from a randomized, placebo-controlled, multicenter study carried out at 11 secondary care centers and a longitudinal single-center study on healthy pregnant women in Norway. Participants A total of 262 women with PCOS and 119 controls. Intervention The participants with PCOS were randomly assigned to metformin (2 g daily) or placebo, from first trimester to delivery. Main Outcome Measures Androstenedione (A4), testosterone (T), sex-hormone binding globulin (SHBG), and free testosterone index (FTI) at 4 time points in pregnancy. Results Women with PCOS versus healthy controls had higher A4, T, and FTI, and lower SHBG at all measured time points in pregnancy. In the overall cohort of women with PCOS, metformin had no effect on A4, T, SHBG, and FTI. In subgroup analyses, metformin reduced A4 (P = 0.019) in nonobese women. Metformin also reduced A4 (P = 0.036), T (P = 0.023), and SHBG (P = 0.010) levels through pregnancy in mothers with a male fetus. Conclusion Metformin had no effect on maternal androgens in PCOS pregnancies. In subgroup analyses, a modest androgen-lowering effect was observed in nonobese women with PCOS. In PCOS women carrying a male fetus, metformin exhibited an androgen-lowering effect.

Introduction: During pregnancy, maternal cortisol levels are increased 3-fold by the third trimester. The enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD, isoforms 1 and 2) regulates the balance between cortisol and cortisone levels. Perfluoroalkyl substances (PFAS) have been reported to inhibit 11β-HSD1 and more potently 11β-HSD2, which could lead to reduced levels of cortisol and more extensively cortisone.Aim: The aim of this work is to investigate a possible effect of early pregnancy PFAS exposure on late pregnancy activity of 11β-HSD1 and 11β-HSD2 assessed by cortisol and cortisone levels in diurnal urine (dU) and blood samples.Methods: This study is part of the prospective cohort study, Odense Child Cohort (OCC). A total of 1628 pregnant women had serum (S) concentrations of 5 PFAS (perfluorooctanoic acid [PFOA], perfluorooctane sulfonic acid [PFOS], perfluorohexane sulfonic acid [PFHxS], perfluorononanoic acid [PFNA], and perfluorodecanoic acid (PFDA)) measured in the first trimester (median gestational week, GW 11). dU cortisol and cortisone (n = 344) and S-cortisol (n = 1048) were measured in the third trimester (median GW 27).Results: In multiple regression analyses, a 2-fold increase in S-PFOS was significantly associated with lower dU-cortisone (β = –9.1%, P < .05) and higher dU-cortisol/dU-cortisone (dU-C/C) (β = 9.3%, P < .05). In crude models, a doubling in PFOS, PFOA, PFHxS, and PFNA concentrations were associated with a significant increase in S-cortisol; however, these associations became insignificant after adjustment.Conclusion: Early pregnancy maternal S-PFAS were inversely associated with late pregnancy dU-cortisone, indicating reduced activity of 11β-HSD2.

Introduction: The hypothalamic-pituitary-adrenal axis function in depression has been the subject of considerable interest, and its function has been tested with a variety of methods. We investigated associations between saliva cortisol at awakening and the 24-h urine cortisol output, both measured at study baseline, with endpoint depression scores. Methods: Patients were admitted to a psychiatric inpatient ward with a major depressive episode and were started on fixed duloxetine treatment. They delivered saliva samples at awakening and 15, 30, and 60 min post-awakening and sampled urine for 24 h. Subsequently, they started a daily exercise program maintained for a 9-week period. Clinician-rated depression severity was blindly assessed with the Hamilton Depression Rating 6-item subscale (HAM-D₆). The cortisol awakening response was quantified by the area under the curve with respect to the ground (AUC_G) and with respect to the rise (AUC_I) using saliva cortisol levels in the 1-h period after awakening. Analysis of expected associations between depression severity, AUC_G, AUC_I, exercise, and 24-h cortisol output was performed in a general linear model. Results: In all, 35 participants delivered saliva or 24-h urine samples. The mean age was 49.0 years (SD = 11.0) with 48.6% females with a mean baseline HAM-D₆ score of 12.2 (SD = 2.3). In a statistical model investigating the association between HAM-D₆ at week 9 as a dependent variable and AUC_I, concurrent HAM-D₆, gender, smoking, and exercise volume as covariates, we found a significant effect of AUC_I, concurrent HAM-D₆, and exercise. The following statistics were found: AUC_I (regression coefficient 0.008; F value = 9.1; p = 0.007), concurrent HAM-D₆ (regression coefficient 0.70; F value = 8.0; p = 0.01), and exercise (regression coefficient −0.005; F value = 5.7; p = 0.03). The model had an R² of 0.43. The association between HAM-D₆ endpoint scores and the AUC_I showed that higher AUC_I values predicted higher HAM-D₆ endpoint values. The association between HAM-D₆ endpoint scores and the exercise level showed that a high exercise level was associated with lower HAM-D₆ endpoint values. Conclusion: The results thus showed that high AUC_I values predicted less improvement of depression and high exercise levels predicted more improvement of depression. These findings need to be confirmed in larger samples to test if more covariates can improve prediction of depression severity.

Surgical site infection following spine surgery is associated with increased morbidity and mortality. Perioperative antibiotic prophylaxis is a key factor in lowering the risk of acquiring an infection. Previous studies have assessed perioperative cefuroxime concentrations in the anterior column of the cervical spine with an anterior surgical approach. However, the majority of surgeries are performed in the posterior column and many surgeries involve the lumbar spine. The objective of this study was to compare the perioperative tissue concentrations of cefuroxime in the anterior and posterior column during lumbar spine surgery with a posterior surgical approach. In vivo experimental pharmacokinetic study of cefuroxime concentrations in an acute preclinical porcine model. The lumbar vertebral column was exposed from L1 to L5 in 8 female pigs. Microdialysis catheters were placed for sampling in the anterior column (vertebral body) and posterior column (posterior arch) within the same vertebra (L5). Cefuroxime (1.5 g) was administered intravenously. Microdialysates and plasma samples were continuously obtained over 8 hours. Cefuroxime concentrations were quantified by Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry. The primary endpoint was the time above the cefuroxime clinical breakpoint minimal inhibitory concentration (T>MIC) for Staphylococcus aureus of 4 µg/mL. The secondary endpoint was tissue penetration (AUC_tissue/AUC_plasma). Mean T>MIC 4 µg/mL (95% confidence interval) was 123 min (105-141) in plasma, 97 min (79-115) in the anterior column and 93 min (75-111) in the posterior column. Tissue penetration (95% confidence interval) was incomplete for both the anterior column 0.48 (0.40-0.56) and posterior column 0.40 (0.33-0.48). T>MIC was comparable between the anterior and posterior column. Mean cefuroxime concentrations decreased below the clinical breakpoint minimal inhibitory concentration for S. aureus of 4 µg/mL after 123 minutes (plasma), 97 minutes (anterior column) and 93 minutes (posterior column). This is shorter than the duration of most lumbar spine surgeries, and therefore alternative dosing regimens should be considered in posterior open lumbar spine surgeries lasting more than 1.5 hours. Open lumbar spine surgery often involves extensive soft tissue dissection, stripping and retraction of the paraspinal muscles which may impair the local blood flow exposing the lumbar vertebra to postoperative infections. A single intravenous administration of 1.5 g cefuroxime only provided sufficient prophylactic target tissue concentrations in the vertebra of the lumbar spine for up to 1.5 hours.

Background: Synthetic glucocorticoid exposure in late pregnancy may be associated with higher blood pressure in offspring. We hypothesized that endogenous cortisol in pregnancy relates to offspring blood pressure (OBP). Objective: To investigate associations between maternal cortisol status in third trimester pregnancy and OBP. Methods: We included 1317 mother-child pairs from Odense Child Cohort, an observational prospective cohort. Serum (s-) cortisol and 24-hour urine (u-) cortisol and cortisone were assessed in gestational week 28. Offspring systolic blood pressure and diastolic blood pressure were measured at age 3, 18 months, and 3 and 5 years. Associations between maternal cortisol and OBP were examined by mixed effects linear models. Results: All significant associations between maternal cortisol and OBP were negative. In boys in pooled analyses, 1 nmol/L increase in maternal s-cortisol was associated with average decrease in systolic blood pressure (β=−0.003 mmHg [95% CI, −0.005 to −0.0003]) and diastolic blood pressure (β=−0.002 mmHg [95% CI, −0.004 to −0.0004]) after adjusting for confounders. At 3 months of age, higher maternal s-cortisol was significantly associated with lower systolic blood pressure (β=−0.01 mmHg [95% CI, −0.01 to −0.004]) and diastolic blood pressure (β=−0.010 mmHg [95% CI, −0.012 to −0.011]) in boys after adjusting for confounders, which remained significant after adjusting for potential intermediate factors. Conclusions: We found temporal sex dimorphic negative associations between maternal s-cortisol levels and OBP, with significant findings in boys. We conclude that physiological maternal cortisol is not a risk factor for higher blood pressure in offspring up to 5 years of age.