The OPTIMIST study: optimisation of cost effectiveness through individualised FSH stimulation dosages for IVF treatment. A randomised controlled trial

Contains fulltext : 109739.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Costs of in vitro fertilisation (IVF) are high, which is partly due to the use of follicle stimulating hormone (FSH). FSH is usually administered in a standard dose. However, due to differences in ovarian reserve between women, ovarian response also differs with potential negative consequences on pregnancy rates. A Markov decision-analytic model showed that FSH dose individualisation according to ovarian reserve is likely to be cost-effective in women who are eligible for IVF. However, this has never been confirmed in a large randomised controlled trial (RCT). The aim of the present study is to assess whether an individualised FSH dose regime based on an ovarian reserve test (ORT) is more cost-effective than a standard dose regime. METHODS/DESIGN: Multicentre RCT in subfertile women indicated for a first IVF or intracytoplasmic sperm injection cycle, who are aged < 44 years, have a regular menstrual cycle and no major abnormalities at transvaginal sonography. Women with polycystic ovary syndrome, endocrine or metabolic abnormalities and women undergoing IVF with oocyte donation, will not be included. Ovarian reserve will be assessed by measuring the antral follicle count. Women with a predicted poor response or hyperresponse will be randomised for a standard versus an individualised FSH regime (150 IU/day, 225-450 IU/day and 100 IU/day, respectively). Participants will undergo a maximum of three stimulation cycles during maximally 18 months. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months after randomisation. Secondary outcomes are parameters for ovarian response, multiple pregnancies, number of cycles needed per live birth, total IU of FSH per stimulation cycle, and costs. All data will be analysed according to the intention-to-treat principle. Cost-effectiveness analysis will be performed to assess whether the health and associated economic benefits of individualised treatment of subfertile women outweigh the additional costs of an ORT. DISCUSSION: The results of this study will be integrated into a decision model that compares cost-effectiveness of the three dose-adjustment strategies to a standard dose strategy. The study outcomes will provide scientific foundation for national and international guidelines. TRIAL REGISTRATION: NTR2657

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Modeling and experimental evaluation of a rotary peristaltic magnetorheological fluid device with low off-state torque for haptic interfaces

This article presents a novel rotary magnetorheological fluid device with inherently low off-state torque. The working principle of the device is similar to peristaltic pumps except the fluid remains inside the device and circulates continuously. Unlike other continuous rotation magnetorheological fluid devices, which operate in shear mode, the proposed device works in pressure driven flow mode. A proof of concept prototype with arbitrary dimensions is built and experimentally evaluated. Measured off-state torque is as low as 20 N.mm. Analytical model of the resistant torque and finite element simulations of the magnetic circuit are presented and validated with the experimental results. Using these models, an optimal device with similar off-state characteristics can be designed to fulfill specific requirements of size, weight, power and on-state torque. The proposed concept is promising especially for use in high precision haptic interfaces that require stability and transparency at the lower end of force spectrum. © 2018, The Brazilian Society of Mechanical Sciences and Engineering

A retrospective clinical, radiographic and microbiological study of periodontal conditions of teeth with and without crowns Um estudo retrospectivo clínico, radiográfico e microbiológico das condições periodontais de dentes com e sem coroas

The aim of this study was to evaluate retrospectively the periodontal conditions of teeth with fixed crowns that had been in place from 3 to 5 years before the study was conducted. Forty individuals were recalled for a follow-up visit. Full-mouth clinical examinations were carried out and Visible Plaque Index (VPI), Gingival Bleeding Index (GBI), Probing Pocket Depth (PPD), and clinical attachment level (CAL) were assessed in 6 sites per tooth. Parallel radiographs were also taken and blindly analyzed by a digital caliper (distance between the apex and the bone crest). BANA tests were performed. A contra-lateral sound tooth was considered the control. Mean values were obtained and Wilcoxon and paired sample t tests were used to compare the test and control sites. Crowns had a mean VPI value of 30.42% as compared to 49.17% for sound teeth. The GBI was 33.33% and 26.25% for test and control teeth respectively. Assessment of PPD revealed values of 2.30 and 2.14 mm, and assessment of CAL revealed averages of 2.02 and 1.89 mm for test and control teeth respectively. The mean values for radiographic distances were 12.73 and 13.67 mm, and for the BANA test, 67.50 and 50.00 for sound and crowned teeth, respectively. Statistically significant differences were observed for all parameters except for CAL and for the BANA test. It may be concluded that, with the methods used in the present study, crowns may be associated with more signs of inflammation, however not with periodontal breakdown.<br>O objetivo deste estudo foi avaliar retrospectivamente as condições periodontais de pacientes com coroas fixas colocadas de 3 a 5 anos antes da realização da pesquisa. Quarenta indivíduos foram rechamados. Exames clínicos de toda a boca foram realizados avaliando-se Índice de Placa Visível (IPV), Índice de Sangramento Gengival (ISG), Profundidade de Sondagem (PS) e Nível Clínico de Inserção (NCI) em 6 sítios por dente. Radiografias paralelas foram obtidas e analisadas cegamente por paquímetro digital (distância do ápice à crista óssea). Testes BANA foram realizados. Um dente hígido contralateral foi considerado como controle. Valores médios foram obtidos e testes de Wilcoxon e t pareado foram utilizados para comparar os sítios teste e controle. Coroas apresentaram um valor médio de IPV de 30,42%, comparado com 49,17% para dentes hígidos. O ISG foi de 33,33% e 26,25% para dentes com coroas e hígidos, respectivamente. A PS revelou valores de 2,30 e 2,14 mm e a análise do NCI demonstrou médias de 2,02 e 1,89 mm para dentes teste e controle, respectivamente. Os valores médios para as distâncias radiográficas foram de 12,73 e 13,67 mm, e para o teste BANA, de 67,50 e 50,00 para dentes hígidos e com coroas, respectivamente. Diferenças estatisticamente significantes foram observadas para todos os parâmetros, exceto para NCI e para o teste BANA. Pode-se concluir que, com os métodos utilizados no presente estudo, coroas podem ser associadas a mais sinais de inflamação, entretanto não com destruição periodontal