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Researchers are increasingly using insights derived from large-scale, electronic healthcare data to inform drug development and provide human validation of novel treatment pathways and aid in drug repurposing/repositioning. The objective of this study was to determine whether treatment of patients with multiple sclerosis with dimethyl fumarate, an activator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, results in a change in incidence of type 2 diabetes and its complications. This retrospective cohort study used administrative claims data to derive four cohorts of adults with multiple sclerosis initiating dimethyl fumarate, teriflunomide, glatiramer acetate or fingolimod between January 2013 and December 2018. A causal inference frequentist model averaging framework based on machine learning was used to compare the time to first occurrence of a composite endpoint of type 2 diabetes, cardiovascular disease or chronic kidney disease, as well as each individual outcome, across the four treatment cohorts. There was a statistically significantly lower risk of incidence for dimethyl fumarate versus teriflunomide for the composite endpoint (restricted hazard ratio [95% confidence interval] 0.70 [0.55, 0.90]) and type 2 diabetes (0.65 [0.49, 0.98]), myocardial infarction (0.59 [0.35, 0.97]) and chronic kidney disease (0.52 [0.28, 0.86]). No differences for other individual outcomes or for dimethyl fumarate versus the other two cohorts were observed. This study effectively demonstrated the use of an innovative statistical methodology to test a clinical hypothesis using real-world data to perform early target validation for drug discovery. Although there was a trend among patients treated with dimethyl fumarate towards a decreased incidence of type 2 diabetes, cardiovascular disease and chronic kidney disease relative to other disease-modifying therapies–which was statistically significant for the comparison with teriflunomide–this study did not definitively support the hypothesis that Nrf2 activation provided additional metabolic disease benefit in patients with multiple sclerosis. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between adherence to glucose-lowering agents and patient outcomes, including costs, acute-care resource utilization, and complications, in an older, type 2 diabetic population. Data and methods: The study used Truven's Medicare Supplemental database from July 1, 2009 to June 30, 2014. Patients aged 65 years or older were included if they had at least two type 2 diabetes diagnoses and received a glucose-lowering agent from July 1, 2010 through June 30, 2011. Multivariable analyses examined the relationships among 3-year patient outcomes and levels of adherence, proxied by the proportion of days covered. Outcomes included all-cause medical costs, diabetes-related medical costs, acute-care resource utilization, and acute complications. Results: In this study (N=123,235), higher adherence was linked to reduced costs and improved health outcomes. For example, comparing an individual with adherence of proportion of days covered <20% to one with proportion of days covered ⩾80% illustrates an average saving of $28,824 in total 3-year costs. Furthermore, a 1% increase in adherence among 1,000 patients was associated with all-cause savings of $65,464 over 3 years. The probability of a hospitalization, an emergency room (ER) visit, or an acute complication decreased monotonically as adherence levels got higher, as did the number of hospitalizations, ER visits, and days hospitalized (P<0.005). Conclusion: Higher adherence was associated with substantially less need for acute care, as indicated by a lowered probability of hospitalization or ER use, a reduced risk of an acute complication, and a decreased number of hospitalizations, ER visits, and days hospitalized. Higher adherence was also generally associated with lower all-cause and diabetes-related total costs, despite higher drug costs. These lower total costs were driven by the diminished acute care and outpatient costs. Results suggest that higher glucose-lowering agent adherence is associated with significant benefits for payers and older patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Purpose: Pharmaceutical formulation and treatment process attributes, such as dose frequency and route of administration, can have an impact on quality of life, treatment adherence, and disease outcomes. The aim of this literature review was to examine studies on preferences for pharmaceutical treatment process attributes, focusing on research in diabetes, oncology, osteoporosis, and autoimmune disorders. Methods: The literature search focused on identifying studies reporting preferences for attributes of the pharmaceutical treatment process. Studies were required to use formal quantitative preference assessment methods, such as utility valuation, conjoint analysis, or contingent valuation. Searches were conducted using Medline, EMBASE, Cochrane Library, Health Economic Evaluation Database, and National Health Service Economic Evaluation Database (January 1993-October 2013). Results: A total of 42 studies met inclusion criteria: 19 diabetes, nine oncology, five osteoporosis, and nine autoimmune. Across these conditions, treatments associated with shorter treatment duration, less frequent administration, greater flexibility, and less invasive routes of administration were preferred over more burdensome or complex treatments. While efficacy and safety often had greater relative importance than treatment process, treatment process also had a quantifiable impact on preference. In some instances, particularly in diabetes and autoimmune disorders, treatment process attributes had greater relative importance than some or all efficacy and safety attributes. Some studies suggested that relative importance of treatment process depends on disease (eg, acute vs chronic) and patient (eg, injection experience) characteristics. Conclusion: Despite heterogeneity in study methods and design, some general patterns of preference clearly emerged. Overall, the results of this review suggest that treatment process has a quantifiable impact on preference and willingness to pay for treatment, even in many situations where safety and efficacy were the primary concerns. Patient preferences for treatment process attributes can inform drug development decisions to better meet the needs of patients and deliver improved outcomes. [ABSTRACT FROM AUTHOR]

Objective: To use a discrete choice experiment (DCE) to evaluate preferences for the actual treatment features and overall profiles of two injectable glucagon-like peptide-1 receptor agonists (dulaglutide and liraglutide) among patients with type 2 diabetes mellitus (T2DM) in the UK. Methods: In-person interviews were conducted in the UK to administer a DCE to patients with self-reported T2DM, naïve to treatment with injectable medications. The DCE examined six attributes of T2DM treatment each described by two levels: "dosing frequency," "hemoglobin A1c change," "weight change," "type of delivery system," "frequency of nausea," and "frequency of hypoglycemia." Part-worth utilities were estimated using random effects logit models and were used to calculate relative importance (RI) values for each attribute. A chi-square test was used to determine differences in preferences for dulaglutide versus liraglutide profiles. Results: A total of 243 participants [mean age: 60.5 (standard deviation 10.9) years; 76.1% male; mean body mass index: 29.8 (standard deviation 5.4) kg/m2] completed the study. RI values for the attributes in rank order were: "dosing frequency" (41.6%), "type of delivery system" (35.5%), "frequency of nausea" (10.4%), "weight change" (5.9%), "hemoglobin A1c change" (3.6%), and "frequency of hypoglycemia" (3.0%). Significantly more participants preferred the dulaglutide profile (83.1%) compared with the liraglutide profile (16.9%; P 0.0001). Conclusion: This study elicited patients' preferences for attributes and levels representing the actual characteristics of two specific glucagon-like peptide-1 medications. In this context, dosing frequency and type of delivery system were most important, accounting for over 75% of the RI. While previous studies have identified efficacy as highly important in T2DM medication decisions, this study suggests that when differences in efficacy between medications are small, other treatment features (eg, dosing frequency and delivery system) are of much greater importance to patients. [ABSTRACT FROM AUTHOR]

The paper reviews evidence from the health care professions about the quality and accessibility of general practice in London, which suggests that inner London is less well served than elsewhere, and recommends changes to the organization and equipment of inner London practice. Results from a community survey in north-east London are presented to show how the views about general practice among residents in a typical inner city district compared with those in a suburban area. The results suggest that while the respondents were generally satisfied with their doctor's practice, a significant minority were dissatisfied, particularly in the inner city. Some of the respondents' views seemed to differ from the model of desirable general practice suggested by the policy literature. In particular, single-handed practice was more popular with patients than group practice. The resuits reflect the importance to patients of good personal rapport and communication with their doctor, which seemed to them the most significant quality of general practice. The implications for policies to improve inner city practice are considered. [ABSTRACT FROM PUBLISHER]

Objectives: Examine the association between adherence to glucose-lowering agents (GLAs) and patient outcomes in an adult type 2 diabetes (T2D) population., Study Design: Retrospective analysis., Methods: Truven's Commercial Claims and Encounters database supplied data from July 1, 2009, to June 30, 2014. Patients 18 to 64 years with T2D were included if they received a GLA from July 1, 2010, through June 30, 2011. Multivariable analyses examined the relationships among 3-year patient outcomes and adherence, defined as proportion of days covered 80% or more. Outcomes included all-cause medical costs, acute care resource utilization, and acute complications., Results: Although there was no statistically significant difference in total costs when comparing adherent and nonadherent patients ($38,633 vs $38,357; P = .0720), acute care costs ($12,153 vs $8233; P <.0001) and outpatient costs ($16,964 vs $15,457; P <.0001) were significantly lower for adherent patients. Adherence was also associated with a lower probability of hospitalization (22.71% vs 17.65%; P <.0001) and emergency department (ED) visits (45.61% vs 38.47%; P <.0001), fewer hospitalizations (0.40 vs 0.27; P <.0001) and ED visits (1.23 vs 0.83; P <.0001), and a shorter hospital length of stay (2.16 vs 1.25 days; P <.0001). Adherent patients were also less likely to be diagnosed with an acute complication in the 3-year post period (12.54% vs 9.64%; P <.0001)., Conclusions: Compared with nonadherence, adherence to GLAs among patients with T2D was associated with a significant reduction in acute care costs and resource utilization, outcomes that may positively impact the welfare of patients.