Relative effectiveness and cost-effectiveness of the midwifery-led care in Nova Scotia, Canada: A retrospective, cohort study.

OBJECTIVES: To compare neonatal and maternal outcomes, and the relative risk of interventions between mothers attended to by midwives, general practitioners, and obstetricians, and to assess the cost-effectiveness of the employee-model of midwifery-led care in Nova Scotia, Canada, when compared with general practitioners. DESIGN, SETTING, AND PARTICIPANTS: The study was a retrospective cohort study involving routinely collected clinical and administrative data from all low-risk births from January 1st, 2013 to December 31st, 2017. There were 24,662 observations. MEASUREMENTS: Descriptive statistics were used to summarise the mother's socio-demographic characteristics. We used a nearest-neighbour matching estimator in assessing differences in outcomes, and generalized linear models in the estimation of the risks of interventions, adjusting for potential confounders. An analytic decision tree served as the vehicle for the cost-effectiveness analysis, assessed using the net monetary benefit approach. All health care resources utilized were measured and valued. Neonatal intensive care admissions avoided was the measure of outcome. We performed probabilistic sensitivity and subgroup analyses. FINDINGS: Mothers attended to by midwives spent less time at the hospital during birth admissions, were less likely to have interventions, instrumental births, and more likely to have exclusive breastfeeding at discharge from birth admission. There were no differences in Apgar scores and neonatal intensive care unit admissions. The employee-model of midwifery-led care was found to be cost-effective. KEY CONCLUSIONS: The midwifery program is both effective and cost-effective for low-risk pregnancies IMPLICATIONS FOR PRACTICE: Increasing the number of midwives will increase access and represents value for money.

Efficacy and safety outcomes in vitamin D supplement users in the fingolimod phase 3 trials.

BACKGROUND: Low serum levels of 25-hydroxyvitamin D have been associated with worse outcomes in multiple sclerosis (MS) patients treated with interferon-beta. Association of vitamin D nutrition on the outcomes of other MS therapies has been studied less. OBJECTIVE: Whether patients in the phase 3 fingolimod trials using vitamin D supplements have better clinical, MRI and safety outcomes than non-users. MATERIALS AND METHODS: Pooled data from phase 3 FREEDOMS trials was analyzed post hoc. Vitamin D use was defined as 'non-users' (n = 562), 'casual users' (n = 157) and 'daily users' (usage 100% time in the study, n = 110). RESULTS: Expanded Disability Status Scale change from baseline to month 24, and annual relapse rate and proportion of patients with relapses were similar across the vitamin D user groups. Proportion of patients free of new/enlarging T2 lesions significantly favored vitamin D 'daily users' versus 'non-users'. Mean number of lesions were lower and proportion of patients free of gadolinium-enhanced T1-lesions were higher in the 'daily users'. At month 12, percent brain volume change was significantly lower in the 'daily users' versus 'non-users' and remained low at month 24 (non-significant). Incidence of depression was lower for vitamin D 'daily users' (non-significant). CONCLUSIONS: We observed improved MRI outcomes on percent brain volume change and proportion of patients free of new/enlarging T2 lesions, and a trend of less depression in the 'daily users' of vitamin D supplement in patients in the FREEDOMS trials.

Targeting αvß3 and αvß5 integrins inhibits pulmonary metastasis in an intratibial xenograft osteosarcoma mouse model.

Osteosarcoma is an aggressive bone cancer that has a high propensity for metastasis to the lungs. Patients with metastatic disease face a very poor prognosis. Therefore, novel therapeutics, efficiently suppressing the metastatic process, are urgently needed. Integrins play a pivotal role in tumor cell adhesion, motility and metastasis. Here, we evaluated αvß3 and αvß5 integrin inhibition with cilengitide as a novel metastasis-suppressive therapeutic approach in osteosarcoma. Immunohistochemical analysis of αvß3 and αvß5 integrins expression in a tissue microarray of tumor specimens collected from osteosarcoma patients revealed that αvß5 integrin is mainly found on tumor cells, whereas αvß3 is predominantly expressed by stromal cells. In vitro functional assays demonstrated that cilengitide dose-dependently inhibited de novo adhesion, provoked detachment and inhibited migration of osteosarcoma cell lines. Cilengitide induced a decline in cell viability, blocked the cell cycle in the G1 phase and caused anoikis by activation of the Hippo pathway. In a xenograft orthotopic mouse model cilengitide minimally affected intratibial primary tumor growth but, importantly, suppressed pulmonary metastasis. The data demonstrate that targeting αvß3 and αvß5 integrins in osteosarcoma should be considered as a novel therapeutic option for patients with metastatic disease.