Tzeyu L. Michaud

The Comparative Safety of Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis: A Meta-analysis Update of 44 Trials

OBJECTIVE The study objective was to evaluate and update the safety data from randomized controlled trials of tumor necrosis factor inhibitors in patients treated for rheumatoid arthritis. METHODS A systematic literature search was conducted from 1990 to May 2013. All studies included were randomized, double-blind, controlled trials of patients with rheumatoid arthritis that evaluated adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab treatment. The serious adverse events and discontinuation rates were abstracted, and risk estimates were calculated by Peto odds ratios (ORs). RESULTS Forty-four randomized controlled trials involving 11,700 subjects receiving tumor necrosis factor inhibitors and 5901 subjects receiving placebo or traditional disease-modifying antirheumatic drugs were included. Tumor necrosis factor inhibitor treatment as a group was associated with a higher risk of serious infection (OR, 1.42; 95% confidence interval [CI], 1.13-1.78) and treatment discontinuation due to adverse events (OR, 1.23; 95% CI, 1.06-1.43) compared with placebo and traditional disease-modifying antirheumatic drug treatments. Specifically, patients taking adalimumab, certolizumab pegol, and infliximab had an increased risk of serious infection (OR, 1.69, 1.98, and 1.63, respectively) and showed an increased risk of discontinuation due to adverse events (OR, 1.38, 1.67, and 2.04, respectively). In contrast, patients taking etanercept had a decreased risk of discontinuation due to adverse events (OR, 0.72; 95% CI, 0.55-0.93). Although ORs for malignancy varied across the different tumor necrosis factor inhibitors, none reached statistical significance. CONCLUSIONS These meta-analysis updates of the comparative safety of tumor necrosis factor inhibitors suggest a higher risk of serious infection associated with adalimumab, certolizumab pegol, and infliximab, which seems to contribute to higher rates of discontinuation. In contrast, etanercept use showed a lower rate of discontinuation. These data may help guide clinical comparative decision making in the management of rheumatoid arthritis.

Does telemedicine improve treatment outcomes for diabetes? A meta-analysis of results from 55 randomized controlled trials.

AIMS To assess the overall effect of telemedicine on diabetes management and to identify features of telemedicine interventions that are associated with better diabetes management outcomes. METHODS Hedgess g was estimated as the summary measure of mean difference in HbA1c between patients with diabetes who went through telemedicine care and those who went through conventional, non-telemedicine care using a random-effects model. Q statistics were calculated to assess if the effect of telemedicine on diabetes management differs by types of diabetes, age groups of patients, duration of intervention, and primary telemedicine approaches used. RESULTS The analysis included 55 randomized controlled trials with a total of 9258 patients with diabetes, out of which 4607 were randomized to telemedicine groups and 4651 to conventional, non-telemedicine care groups. The results favored telemedicine over conventional care (Hedgess g=-0.48, p<0.001) in diabetes management. The beneficial effect of telemedicine were more pronounced among patients with type 2 diabetes (Hedgess g=-0.63, p<0.001) than among those with type 1 diabetes (Hedgess g=-0.27, p=0.027) (Q=4.25, p=0.04). CONCLUSIONS Compared to conventional care, telemedicine is more effective in improving treatment outcomes for diabetes patients, especially for those with type 2 diabetes.

Cost-Effectiveness of a Statewide Campaign to Promote Aspirin Use for Primary Prevention of Cardiovascular Disease.

Background The U.S. Preventive Services Task Force in 2009 recommended increased aspirin use for primary prevention of cardiovascular disease (CVD) in men ages 45 to 79 years and women ages 55 to 79 years for whom benefit outweighs risk. This study estimated the clinical efficacy and cost‐effectiveness of a statewide public and health professional awareness campaign to increase regular aspirin use among the target population in Minnesota to reduce first CVD events. Methods and Results A state‐transition Markov model was developed, adopting a payer perspective and lifetime time horizon. The main outcomes of interest were quality‐adjusted life years, costs, and the number of CVD events averted among those without a prior CVD history. The model was based on real‐world data about campaign effectiveness from representative state‐specific aspirin use and event rates, and estimates from the scholarly literature. Implementation of a campaign was predicted to avert 9874 primary myocardial infarctions in men and 1223 primary ischemic strokes in women in the target population. Increased aspirin use was associated with as many as 7222 more major gastrointestinal bleeding episodes. The cost‐effectiveness analysis indicated cost‐saving results for both the male and female target populations. Conclusions Using current U.S. Preventive Services Task Force recommendations, a state public and health professional awareness campaign would likely provide clinical benefit and be economically attractive. With clinician adjudication of individual benefit and risk, mechanisms can be made available that would facilitate achievement of aspirins beneficial impact on lowering risk of primary CVD events, with minimization of adverse outcomes.

The risk of incident mild cognitive impairment and progression to dementia considering mild cognitive impairment subtypes

Background: It remains unclear how demographic and clinical characteristics are related to the risk of incident mild cognitive impairment (MCI) by its subtypes. Moreover, the contribution of the subtypes of incident MCI to the progression to dementia remains puzzling. Methods: We used data collected by the National Alzheimer Coordinating Center. Our analysis sample included cognitively normal subjects at baseline. The associations were examined using competing-risks survival regression models and Cox proportional hazards models. Results: About 16.3% of subjects developed incident MCI of whom 15.8% progressed to Alzheimer disease (overall mean follow-up of 4.3 years). The risk of incident amnestic MCI (aMCI) was greater in subjects with 1 copy (subhazard ratio [SHR]: 1.23; 95% CI: 1.00–1.50) or 2 copies (SHR: 2.14; 95% CI: 1.49–3.05) of the APOE ε4 allele than in those who had no ε4 allele. Multiple-domain aMCI patients were more likely to progress to dementia than single-domain aMCI patients (hazard ratio: 2.14; 95% CI: 1.28–3.58). Conclusions: Cognitively normal subjects with an APOE ε4 allele had a higher likelihood of developing aMCI and the MCI subtype was associated with the dementia subtype. Our findings provide important information about practical indicators for the prediction of cognitive decline.


Risk Stratification Using Cerebrospinal Fluid Biomarkers in Patients with Mild Cognitive Impairment: An Exploratory Analysis.

BACKGROUND Cerebrospinal fluid (CSF) biomarkers can distinguish Alzheimers disease (AD) patients from normal controls; however, their interpretation and potential for use in patients with mild cognitive impairment (MCI) remains unclear. OBJECTIVE To examine whether biomarker levels allow for risk stratification among MCI patients who are at increased risk to develop AD, thus allowing for improved targeting of early interventions for those whose risk are higher. METHODS We analyzed data from the Alzheimers Disease Neuroimaging Initiative on MCI patients (n = 195) to estimate their risk of developing AD for up to 6 years on the basis of baseline CSF biomarkers. We used time-dependent receiver operating characteristic analysis to identify the best combination of biomarkers to discriminate those who converted to AD from those who remained stable. We used these data to construct a multi-biomarker score and estimated the risk of progression to AD for each quintile of the multi-biomarker score. RESULTS We found that Aβ(1-42) and P-tau(181p) were the best combination among CSF biomarkers to predict the overall risk of developing AD among MCI patients (area under the curve = 0.77). The hazard ratio of developing AD among MCI patients with high-risk (3rd-5th quintiles) biomarker levels was about 4 times greater than MCI patients with low-risk (1st quintile) levels (95% confidence interval, 1.93-7.26). CONCLUSION Our study identifies MCI patients at increased risk of developing AD by applying a multi-biomarker score using CSF biomarker results. Our findings may be of value to MCI patients and their clinicians for planning purposes and early intervention as well as for future clinical trials.

For What Illnesses Is a Disease Management Program Most Effective

Objective:We examined the impact of a disease management (DM) program offered at the University of Minnesota for those with various chronic diseases. Methods:Differences-in-differences regression equations were estimated to determine the effect of DM participation by chronic condition on expenditures, absenteeism, hospitalizations, and avoidable hospitalizations. Results:Disease management reduced health care expenditures for individuals with asthma, cardiovascular disease, congestive heart failure, depression, musculoskeletal problems, low back pain, and migraines. Disease management reduced hospitalizations for those same conditions except for congestive heart failure and reduced avoidable hospitalizations for individuals with asthma, depression, and low back pain. Disease management did not have any effect for individuals with diabetes, arthritis, or osteoporosis, nor did DM have any effect on absenteeism. Conclusions:Employers should focus on those conditions that generate savings when purchasing DM programs. Clinical Significance:This study suggests that the University of Minnesotas DM program reduces hospitalizations for individuals with asthma, cardiovascular disease, depression, musculoskeletal problems, low back pain, and migraines. The program also reduced avoidable hospitalizations for individuals with asthma, depression, and low back pain.

Social disparities in exposure to point-of-sale cigarette marketing

While most ecological studies have shown that higher levels of point-of-sale (POS) cigarette marketing are associated with larger proportions of residents from lower socioeconomic and minority backgrounds in neighborhoods, there are no studies that examine individual-level social disparities in exposure to POS cigarette marketing among smokers in the United States. Our aim was to examine these disparities in a Midwestern metropolitan area in the United States. We conducted a telephone survey to collect data on 999 smokers. Cigarette marketing was measured by asking respondents three questions about noticing advertisements, promotions, and displays of cigarettes within their respective neighborhoods. The questions were combined to create a summated scale. We estimated ordered logistic regression models to examine the association of sociodemographic variables with exposure to POS cigarette marketing. Adjusted results showed that having a lower income (p < 0.003) and belonging to a race/ethnicity other than “non-Hispanic White” (p = 0.011) were associated with higher levels of exposure to POS cigarette marketing. The results highlight social disparities in exposure to POS cigarette marketing in the United States, which can potentially be eliminated by banning all forms of cigarette marketing.

Using Cerebrospinal Fluid Biomarker Testing to Target Treatment to Patients with Mild Cognitive Impairment: A Cost-Effectiveness Analysis

ObjectiveCerebrospinal fluid (CSF) biomarkers are shown to facilitate a risk identification of patients with mild cognitive impairment (MCI) into different risk levels of progression to Alzheimer’s disease (AD). Knowing a patient’s risk level provides an opportunity for earlier interventions, which could result in potential greater benefits. We assessed the cost effectiveness of the use of CSF biomarkers in MCI patients where the treatment decision was based on patients’ risk level.MethodsWe developed a state-transition model to project lifetime quality-adjusted life-years (QALYs) and costs for a cohort of 65-year-old MCI patients from a US societal perspective. We compared four test-and-treat strategies where the decision to treat was based on a patient’s risk level (low, intermediate, high) of progressing to AD with two strategies without testing, one where no patients were treated during the MCI phase and in the other all patients were treated. We performed deterministic and probabilistic sensitivity analyses to evaluate parameter uncertainty.ResultsTesting and treating low-risk MCI patients was the most cost-effective strategy with an incremental cost-effectiveness ratio (ICER) of US

Cost effectiveness and return on investment of a scalable community weight loss intervention

37,700 per QALY. Our results were most sensitive to the level of treatment effectiveness for patients with mild AD and for MCI patients. Moreover, the ICERs for this strategy at the 2.5th and 97.5th percentiles were US

Dependence Stage and Pharmacoeconomic Outcomes in Patients With Alzheimer Disease

18,900 and US