The treatment of multiple sclerosis (MS) has changed over the last 20 years. All immunotherapeutic drugs target relapsing remitting MS (RRMS) and it still remains a medical challenge in MS to develop a treatment for progressive forms. The most common injectable disease-modifying therapies in RRMS include β-interferons 1a or 1b and glatiramer acetate. However, one of the major challenges of injectable disease-modifying therapies has been poor treatment adherence with approximately 50% of patients discontinuing the therapy within the first year. Herein, we go back to the basics to understand the immunopathophysiology of MS to gain insights in the development of new improved drug treatments. We present current disease-modifying therapies (interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, mitoxantrone), humanized monoclonal antibodies (natalizumab, ofatumumab, ocrelizumab, alemtuzumab, daclizumab) and emerging immune modulating approaches (stem cells, DNA vaccines, nanoparticles, altered peptide ligands) for the treatment of MS.
1 March 1997 in Journal of Diabetes and its Complications
Objective: The evidence for the association between obesity and the risk of type 2 diabetes has been derived mainly from the analysis of the degree of obesity. The role of the duration of obesity as an independent risk has not been fully explored. The objective of the present study was to investigate the association between the duration of obesity and the risk of type 2 diabetes.Design: Prospective cohort study.Setting: The Framingham Heart Study (FHS), follow-up from 1948 to 1998.Subjects: A total of 1256 FHS participants who were free from type 2 diabetes at baseline, but were obese on at least two consecutive of the study’s twenty-four biennial examinations, were included. Type 2 diabetes status was collected throughout the 48 years of follow-up of the study. The relationship between duration of obesity and type 2 diabetes was analysed using time-dependent Cox models, adjusting for a number of covariates.Results: The unadjusted hazard ratio (HR) for the risk of type 2 diabetes for men was 1·13 (95 % CI 1·09, 1·17) and for women was 1·12 (95 % CI 1·08, 1·16) per additional 2-year increase in the duration of obesity. Adjustment for sociodemographic variables, family history of diabetes, health behaviour and physical activity made little difference to these HR. For women the evidence of a dose–response relationship was less clear than for men, particularly for women with an older age at obesity onset.Conclusions: The duration of obesity is a relevant risk factor for type 2 diabetes, independent of the degree of BMI.
OBJECTIVE—The objective of this study was to assess the barriers to care for patients with insulin-requiring diabetes in Mozambique and Zambia. RESEARCH DESIGN AND METHODS—We used the Rapid Assessment Protocol for Insulin Access to collect information through interviews, discussions, site visits, and document reviews. Government organizations, health facilities, care givers, and patients were asked about care for people with insulin-requiring diabetes. Between 100 and 200 interviews/discussions per country were undertaken in and around the capital city and the regional capital and in a rural area. RESULTS—Insulin was present in both countries in sufficient quantities, although the financial burden for health services and patients meant that problems with supply exist. There are problems with quantification of needs and equitable distribution of insulin. Problems with availability of syringes and testing equipment were noted, particularly in Mozambique. This lack of tools and infrastructure for diagnosis and follow-up coupled with low levels of health care worker training and lack of diagnostic reagents resulted in a substantial risk of misdiagnosis or failure to detect diabetes. The estimated prevalence of insulin-requiring diabetes differs more than 10-fold between urban and rural areas in Mozambique and 4-fold between Mozambique and Zambia, suggesting that problems in diagnosis and care result in substantial worsening of prognosis for such patients. CONCLUSIONS—Insulin is necessary but not sufficient to improve prognosis for diabetic patients. A Rapid Assessment Protocol methodology can be used to define problems in health care delivery for diabetes. Proper care for insulin-requiring diabetes necessitates health systems able to provide trained personnel, medicines in sufficient quantity, and diagnostic and monitoring facilities.