Recent metformin adherence and the risk of hypoglycaemia in the year following intensification with a sulfonylurea.

AIM: To evaluate whether recent low adherence to metformin monotherapy is associated with hypoglycaemia after addition of a sulfonylurea. METHODS: We assembled a retrospective cohort of veterans who filled a new prescription for metformin between 2001 and 2011 and intensified treatment with a sulfonylurea after ≥1 year of metformin use. We calculated metformin adherence from pharmacy data using the proportion of days covered in the 180-day period before intensification. The primary outcome was hypoglycaemia, defined as a hospitalization or emergency department visit for hypoglycaemia or an outpatient blood glucose measurement <3.3 mmol/l in the year following intensification. Cox proportional hazards models were used to compare the risk of hypoglycaemia between participants with low (<80%) and high (≥80%) adherence. Adherence was also modelled as a continuous variable using restricted cubic splines. RESULTS: Of 187 267 participants who initiated metformin monotherapy, 49 424 added a sulfonylurea after ≥1 year. The median (interquartile range) rate of treatment adherence was 87 (50-100)% and 43% had adherence <80%. Hypoglycaemia rates per 1000 person-years were 23.1 (95% CI 21.1-25.4) and 24.5 (95% CI 22.7-26.4) in participants with low and high adherence, respectively (adjusted hazard ratio 0.95, 95% CI 0.84-1.08). The risk of hypoglycaemia was similar across all levels of adherence when adherence was modelled as a continuous variable. CONCLUSIONS: We found no evidence that past low adherence to metformin monotherapy was associated with hypoglycaemia after intensification with a sulfonylurea.

Early discontinuation of treatment in patients with orthostatic hypotension.

BACKGROUND: Midodrine and fludrocortisone are considered the first-line pharmacologic treatments for orthostatic hypotension (OH). Although OH is thought to require long-term therapy, it is unknown how long patients remain on treatment ("persistence"). METHODS: We assembled a retrospective cohort of patients with OH aged ≥ 50 years enrolled in Tennessee Medicaid (1996-2008), and identified new episodes of midodrine and fludrocortisone use. Follow-up continued from the first medication fill through treatment discontinuation (90 days without medication), change in treatment, death, hospitalization, and loss of enrollment or study end. We compared persistence on treatment using Cox regression models and fludrocortisone as reference. Covariates included demographics, healthcare utilization measurements and co-morbidities. RESULTS: We identified 1704 OH patients, who initiated 1767 episodes of fludrocortisone (1103) or midodrine (664) use. The median age was 69 years, 53% were female and 80% were white. During 738 person years of follow-up, episodes of use ended because of treatment discontinuation in 467 (27% fludrocortisone, 25% midodrine); treatment change in 72 (3% fludrocortisone, 6% midodrine) and death in 53 (3% fludrocortisone, 2% midodrine). Overall median persistence on fludrocortisone and midodrine was 254 (IQR: 119-783) and 259 (IQR: 119-807) days, respectively. The adjusted hazard ratio (aHR) for overall non-persistence on midodrine compared to fludrocortisone was 1.07 (95% CI: 0.90-1.28). CONCLUSIONS: Overall duration of OH treatment with first-line medications was short, and similar for fludrocortisone and midodrine. Further research is warranted to determine the causes of this low persistence. (Words#234).

Incidence and risk factors for progressive multifocal leukoencephalopathy among patients with selected rheumatic diseases.

OBJECTIVE: To ascertain the incidence of progressive multifocal leukoencephalopathy (PML) in patients with selected rheumatic diseases, to describe the characteristics of PML cases occurring in this setting, and to evaluate the extent to which such cases occurred in the context of biologic therapies such as rituximab or tumor necrosis factor antagonists. METHODS: We conducted a large population-based study to describe the incidence and risk factors for PML among patients with rheumatoid arthritis, psoriatic arthritis, psoriasis, juvenile idiopathic arthritis, inflammatory bowel disease, and ankylosing spondylitis using national inpatient and outpatient administrative data from the entire Center for Medicare and Medicaid Services from 2000-2009. Suspected PML cases were identified using hospital discharge diagnosis codes. Risk factors for PML were evaluated using outpatient data ≥6 months prior to PML diagnosis. RESULTS: Among 2,030,578 patients with autoimmune diseases of interest, a total of 53 PML cases were identified (2.6 per 100,000 patients). Most PML cases had human immunodeficiency virus (HIV) and/or cancer. Nine PML cases had evidence for biologic use prior to PML hospitalization, of which 3 had neither HIV nor malignancy and were exposed to biologics within 12 (rituximab) or 6 months (all other biologics) prior to PML diagnosis. PML occurred at an estimated incidence of 0.2 per 100,000 patients with autoimmune diseases who did not have HIV or malignancy. CONCLUSION: PML occurs at a very low incidence among patients with rheumatic diseases but can occur even in the absence of HIV or malignancy.

Comparisons of persistence and durability among three oral antidiabetic therapies using electronic prescription-fill data: the impact of adherence requirements and stockpiling.

Two important challenges are inherent in the design of studies using prescription data from electronic health records: how to define the minimum level of adherence that would qualify as "continuous drug use" and how to handle stockpiling of medications. Generally, the sensitivity of a study's conclusions to these design choices is not analyzed. In our study, covariate adjusted Cox models were used to compare persistence and durability with respect to three common oral antidiabetic therapies in a cohort of 12,697 incident users. Assuming 50% stockpiling, sulfonylurea therapy, as compared with metformin, showed a significantly lower risk of nonpersistence (changing or stopping therapy) when no gap days were allowed (HR 0.95, P = 0.032), no significant difference when 14 gap days were allowed (HR 0.99, P = 0.536), and significantly greater risk of nonpersistence when 30 gap days were allowed (HR 1.05, P = 0.046). All the drug comparisons showed statistically significant effects in both directions, the risk of nonpersistence increasing or decreasing depending on the design parameters.

Changing patterns of medication use in patients with rheumatoid arthritis in a Medicaid population.

OBJECTIVE: To examine changes in patterns of medication utilization in patients with RA. METHODS: Data from Tennessee Medicaid (TennCare) databases (1995-2004) were used to identify adults with both a diagnosis of RA and at least one DMARD prescription each year. Annual age-specific utilization of DMARDs, glucocorticoids, NSAIDs and narcotics was measured on the last day of each year to determine the point prevalence of use of these agents. RESULTS: Records from 23 342 patients with treated RA were analysed. Most patients were females (78%) and white (74%). The median age was 57 yrs (interquartile range: 48-65). The proportion of patients who had a current DMARD prescription on the index date increased from 62% in 1995 to 71% in 2004 (P < 0.001). MTX was the most commonly used DMARD. By the end of 2004, 22% of patients had a current prescription for a biologic, and etanercept represented 51% of all biologic therapies. During the study period, the overall utilization of glucocorticoids decreased from 46% to 38% (P < 0.001), whereas NSAID utilization increased from 33% to 38% (P < 0.001), and use of narcotics increased from 38% to 55% (P < 0.001). A secondary analysis that identified RA patients based on diagnosis codes alone, showed similar patterns, but lower DMARD utilization which increased from 33% to 52% overall and from 0% to 16% for biologics. CONCLUSIONS: The utilization of DMARDs increased in TennCare patients with RA, and by 2004, use of biologics was substantial. Although glucocorticoid utilization decreased, use of both NSAIDs and narcotics increased.

Estimating the undetected burden of influenza hospitalizations in children.

During the 2004-2005 influenza season two independent influenza surveillance systems operated simultaneously in three United States counties. The New Vaccine Surveillance Network (NVSN) prospectively enrolled children hospitalized for respiratory symptoms/fever and tested them using culture and RT-PCR. The Emerging Infections Program (EIP) and a similar clinical-laboratory surveillance system identified hospitalized children who had positive influenza tests obtained as part of their usual medical care. Using data from these systems, we applied capture-recapture analyses to estimate the burden of influenza related-hospitalizations in children aged<5 years. During the 2004-2005 influenza season the influenza-related hospitalization rate estimated by capture-recapture analysis was 8.6/10,000 children aged<5 years. When compared to this estimate, the sensitivity of the prospective surveillance system was 69% and the sensitivity of the clinical-laboratory based system was 39%. In the face of limited resources and an increasing need for influenza surveillance, capture-recapture analysis provides better estimates than either system alone.