Very high prevalence of 25-hydroxyvitamin D deficiency in 6433 UK South Asian adults : Analysis of the UK Biobank Cohort

Acknowledgements This research has been conducted using the UK Biobank Resource under application number 15168. This work was supported by in-house funds from the University of Surrey for payment of the UK Biobank access fee. The UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government and the British Heart Foundation. UK Biobank is hosted by the University of Manchester and supported by the National Health Service (NHS). All the above funders had no role in the design, analysis or writing of the present study. Author contributions were as follows: Formulating the research question(s) (A. L. D., D. J. B., K. R. A., S. L. N.), designing the study (A. L. D., D. J. B., K. R. A., S. A. L.-N.), data collection (not applicable), analysing the data (A. L. D., D. J. B., K. R. A., S. A. L.-N.) and writing the article (A. L. D., D. J. B., K. R. A., S. L. N.). S. A. L.-N. discloses that she is Research Director of D3-TEX limited which holds the UK and Gulf Corporation Council (GCC) patents for the use of UVB transparent clothing to prevent vitamin D deficiency. S. A. L.-N.’s husband William Lanham-New is Managing Director of D3-TEX limited. S. A. L.-N. has received grants from (1) The UK Biotechnology and Biological Sciences Research Council (BBSRC) (project: Ergocalciferol (D2) v. Cholecalciferol (D3) Food Fortification: Comparative Efficiency in Raising 25OHD Status & Mechanisms of Action (D2–D3 Study), BB/I006192/1, £516 823); (2) The UK Food Standards Agency (Project: Vitamin D, Food Intake, Nutrition and Exposure to Sunlight in Southern England (D-FINES) Study, N05064, £600 000); (3) The European Union (Project: Food Based Solutions for optimal vitamin D nutrition and health through the life cycle, Lead Work Package; (4) nutritional requirements for vitamin D during pregnancy, childhood and adolescence using RCTs, FP7-613977-ODIN, Euro 6·2 million) and (5) The UK Ministry of Defence (MoD, £2·4 million). S. L. N. is a current member of the Scientific Advisory Committee for Nutrition (SACN) and a member of the panel who was responsible for the most recent revision of vitamin D recommended nutritional intake guidelines in the UK. She is a board member for the UK Royal Osteoporosis Society and the British Nutrition Foundation. She is Secretary of the Nutrition Society as well as Editor in Chief of the Nutrition Society textbook series. All other authors have no conflict of interest.Peer reviewedPublisher PD

Dietary Protein and Bone Health Across the Life-Course : an updated systematic review and meta-analysis over 40 years

Abstract Purpose: This systematic review and meta-analysis analysed the relationship between dietary protein and bone health across the life-course. Methods: The PubMed database was searched for all relevant human studies from the 1st 4 January 1976 to 22nd January 2016, including all bone outcomes except calcium metabolism. Results: The searches identified 127 papers for inclusion, including 74 correlational studies, 23 fracture or osteoporosis risk studies and 30 supplementation trials. Protein intake accounted for 0 - 4% of areal BMC and areal BMD variance in adults and 0-14% of areal BMC variance in children and adolescents. However, when confounder adjusted (5 studies) adult lumbar spine and femoral neck BMD associations were not statistically significant. There was no association between protein intake and relative risk (RR) of osteoporotic fractures for total (RR(random) = 0.94; 0.72 to 1.23, I2=32%), animal (RR (random) = 0.98; 0.76 to 1.27, I2 = 46%) or vegetable protein (RR (fixed)= 0.97 (0.89 to 1.09, I2 = 15%). In total protein supplementation studies, pooled effect sizes were not statistically significant for LSBMD (total n=255, MD(fixed)=0.04 g/cm2 (0.00 to 0.08, P=0.07), I2=0%) or FNBMD (total n=435, MD(random)=0.01 g/cm2 (-0.03 to 0.05, P=0.59), I2=68%). Conclusions: There appears to be little benefit of increasing protein intake for bone health in healthy adults but there is also clearly no indication of any detrimental effect, at least within the protein intakes of the populations studied (around 0.8-1.3 g/Kg/day). More studies are urgently required on the association between protein intake and bone health in children and adolescents. Key Words: Aging, Epidemiology, IGF-1, Nutrition, Osteoporosis, Die

Vitamin D Status of the British African-Caribbean Residents : Analysis of the UK Biobank Cohort

Funding: This work is part of the PhD of R.M.V., which is funded by the Universities Global Part‐ nership Network, co‐supervised by the Universities of Surrey and Wollongong. Funders did not have a role in the study. The researchers are independent to the funders. All authors take responsibility for the integrity of the data and the accuracy of the data analysis.Peer reviewedPublisher PD

Inflammatory and Angiogenic Factors at Mid-Pregnancy Are Associated with Spontaneous Preterm Birth in a Cohort of Tanzanian Women.

Preterm birth (PTB) is the leading cause of perinatal mortality worldwide, with the greatest burden occurring in resource-constrained settings. Based on the hypothesis that altered placental angiogenesis and inflammation early in pregnancy lead to PTB, we examined whether levels of inflammatory and angiogenic mediators, measured early in pregnancy, were predictive of spontaneous PTB (sPTB).\ud Plasma samples were collected from a prospective cohort of primigravid Tanzanian women between 12-27 weeks gestation. A panel of 18 markers was screened on a training cohort of 426 women. Markers associated with sPTB in the training cohort were repeated in a test cohort of 628 women. All markers were measured by ELISA. In both the training and test cohorts plasma levels of IL-18BP, sICAM-1, sEndoglin and CHI3L1 were elevated and Leptin was lower at enrollment in women who subsequently experienced sPTB. In multivariate analysis women with plasma levels of CHI3L1, C5a, sICAM-1, AngptL3, sEndgolin, sFlt-1 and IL-18BP in the highest quartile had an increased risk of sPTB compared with those in the lowest quartile. Women with Leptin and Ang2 in the highest quartile had a reduced risk of sPTB compared with women in the lowest quartile. Levels of angiogenic and inflammatory mediators measured at mid-pregnancy were associated with subsequent sPTB. These findings provide insight into mechanisms underlying sPTB and suggest biomarkers that may have clinical utility in risk-stratifying pregnancies

Improved results of induction chemoradiation before surgical intervention for selected patients with stage IIIA-N2 non–small cell lung cancer

ObjectiveOptimal management of stage IIIA-N2 non–small cell lung cancer remains controversial. The surgical arm of the North American Intergroup 0139 trial was adopted as the standard treatment for patients with resectable N2 disease at the University Health Network. Results after 7 years of experience are reported.MethodsThis is a retrospective study of consecutive patients with biopsy-proved T1-3 N2 M0 lung cancer who underwent induction chemoradiation before surgical intervention from January 1997 through August 2004. Induction chemotherapy consisted of cisplatin, 50 mg/m2, on days 1 and 8; etoposide, 50 mg/m2, on days 1 to 5, weeks 1 and 5; and concurrent daily external beam radiotherapy to 45 Gy. Lung resection was performed within 6 weeks of completion of chemoradiation, followed by 2 further cycles of consolidation chemotherapy.ResultsBetween January 1997 and August 2004, 40 patients were treated according to this protocol (25% T1, 62.5% T2, 7.5% T3, and 5% T4). Overall and disease-free median survivals were 40 and 37.1 months, respectively, whereas overall and disease-free 3-year survivals were 51.7% and 52.3%, respectively. R0 resection was achieved in 92.5%. The overall operative mortality rate was 7.5% (0% for lobectomy and 27% for pneumonectomy). Notably, all mortalities occurred within the first 2 years of our experience with this regimen.ConclusionChemoradiation before pulmonary resection in carefully selected patients with surgically resectable stage IIIA (N2) non–small cell lung cancer can lead to improved overall and disease-free survival

How are "teaching the teachers" courses in evidence based medicine evaluated? A systematic review

Background Teaching of evidence-based medicine (EBM) has become widespread in medical education. Teaching the teachers (TTT) courses address the increased teaching demand and the need to improve effectiveness of EBM teaching. We conducted a systematic review of assessment tools for EBM TTT courses. To summarise and appraise existing assessment methods for teaching the teachers courses in EBM by a systematic review. Methods We searched PubMed, BioMed, EmBase, Cochrane and Eric databases without language restrictions and included articles that assessed its participants. Study selection and data extraction were conducted independently by two reviewers. Results Of 1230 potentially relevant studies, five papers met the selection criteria. There were no specific assessment tools for evaluating effectiveness of EBM TTT courses. Some of the material available might be useful in initiating the development of such an assessment tool. Conclusion There is a need for the development of educationally sound assessment tools for teaching the teachers courses in EBM, without which it would be impossible to ascertain if such courses have the desired effect

Viral suppression and retention in HIV care during the postpartum period among women living with HIV: a longitudinal multicenter cohort study.

BACKGROUND Low rates of postnatal retention in HIV care and viral suppression have been reported in women living with HIV (WLWH) despite viral suppression at delivery. At the same time, postpartum follow-up is of crucial importance in light of the increasing support offered in many resource-rich countries including Switzerland to WLWH choosing to breastfeed their infant, if optimal scenario criteria are met. METHODS We longitudinally investigated retention in HIV care, viral suppression, and infant follow-up in a prospective multicentre HIV cohort study of WLWH in the optimal scenario who had a live birth between January 2000 and December 2018. Risk factors for adverse outcomes in the first year postpartum were assessed using logistic and proportional hazard models. FINDINGS Overall, WLWH were retained in HIV care for at least six months after 94.2% of the deliveries (694/737). Late start of combination antiretroviral therapy (cART) during the third trimester was found to be the main risk factor for failure of retention in HIV care (crude odds ratio [OR] 3.91; 95% confidence interval [CI], 1.50-10.22; p = 0.005). Among mothers on cART until at least one year after delivery, 4.4% (26/591) experienced viral failure, with illicit drugs use being the most important risk factor (hazard ratio [HR], 13.2; 95% CI, 2.35-73.6; p = 0.003). The main risk factors for not following the recommendations regarding infant follow-up was maternal depression (OR, 3.52; 95% CI, 1.18-10.52; p = 0.024). INTERPRETATION Although the results are reassuring, several modifiable risk factors for adverse postpartum outcome, such as late treatment initiation and depression, were identified. These factors should be addressed in HIV care of all WLWH, especially those opting to breastfeed in resource-rich countries. FUNDING This study has been financed within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (grant #201369), by SHCS project 850 and by the SHCS research foundation

Viral suppression and retention in HIV care during the postpartum period among women living with HIV: a longitudinal multicenter cohort study

BACKGROUND: Low rates of postnatal retention in HIV care and viral suppression have been reported in women living with HIV (WLWH) despite viral suppression at delivery. At the same time, postpartum follow-up is of crucial importance in light of the increasing support offered in many resource-rich countries including Switzerland to WLWH choosing to breastfeed their infant, if optimal scenario criteria are met. METHODS: We longitudinally investigated retention in HIV care, viral suppression, and infant follow-up in a prospective multicentre HIV cohort study of WLWH in the optimal scenario who had a live birth between January 2000 and December 2018. Risk factors for adverse outcomes in the first year postpartum were assessed using logistic and proportional hazard models. FINDINGS: Overall, WLWH were retained in HIV care for at least six months after 94.2% of the deliveries (694/737). Late start of combination antiretroviral therapy (cART) during the third trimester was found to be the main risk factor for failure of retention in HIV care (crude odds ratio [OR] 3.91; 95% confidence interval [CI], 1.50-10.22; p = 0.005). Among mothers on cART until at least one year after delivery, 4.4% (26/591) experienced viral failure, with illicit drugs use being the most important risk factor (hazard ratio [HR], 13.2; 95% CI, 2.35-73.6; p = 0.003). The main risk factors for not following the recommendations regarding infant follow-up was maternal depression (OR, 3.52; 95% CI, 1.18-10.52; p = 0.024). INTERPRETATION: Although the results are reassuring, several modifiable risk factors for adverse postpartum outcome, such as late treatment initiation and depression, were identified. These factors should be addressed in HIV care of all WLWH, especially those opting to breastfeed in resource-rich countries. FUNDING: This study has been financed within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (grant #201369), by SHCS project 850 and by the SHCS research foundation