Impact on glycated haemoglobin of a biological response-based measure of medication adherence.

AIMS: The aim of this study was to examine the relationship between a specific glycated haemoglobin (HbA1c) measurement and a pharmaceutical dispensings-based measure of adherence calculated over the 90 days before each HbA1c measure among patients who have newly initiated metformin therapy. METHODS: We identified 3109 people with type 2 diabetes who initiated metformin as their first-ever antihyperglycaemic drug, analysing all 9918 HbA1c measurements that were taken over the next 2 years. We used an adaptation of the 'proportion of days covered' method for assessing medication adherence that corresponded to an ∼90-day interval preceding an HbA1c measurement, terming the adaptation the 'biological response-based proportion of days covered' (BRB-PDC). To account for multiple observations per patient, we analysed the association between HbA1c and BRB-PDC within the generalized estimating equation framework. Analyses were stratified by HbA1c level before metformin initiation using a threshold of 8% (64 mmol/mol). RESULTS: After multivariable adjustment using 0% adherence as the reference category, BRB-PDC in the range 50-79% was associated with HbA1c values lower by -0.113 [95% confidence interval (CI) -0.202, -0.025] among patients with pre-metformin HbA1c <8%, and by -0.247 (95% CI -0.390, -0.104) among those with HbA1c ≥8% at metformin initiation. Full adherence (≥80%) was associated with HbA1c values lower by -0.175% (95% CI -0.257, -0.093) and by -0.453% (95% CI -0.586, -0.320). CONCLUSIONS: Using this novel short-interval approach that more closely associates adherence with the expected biological response, the association between better adherence and HbA1c levels was considerably stronger than has been previously reported; however, the strength of the impact was dependent upon the HbA1c level before initiating metformin.

Features associated with survival and disease-free survival in early endometrial cancer.

Age, clinical stage, histologic grade, depth of myometrial penetration, adnexal status, peritoneal cytology, and progesterone and estrogen receptor status were available for 139 patients with clinical stage IA, IB, or II endometrial adenocarcinoma who had therapy at Indiana University Hospital or St. Vincent Hospital in Indianapolis. These features were analyzed for their association with survival and disease-free survival. Patients treated at Indiana University Hospital were similar to those from St. Vincent Hospital when comparisons were made by chi 2 test for age, clinical stage, grade, adnexal metastases, peritoneal cytologic results, progesterone receptor status, or estrogen receptor status. However, patients treated at Indiana University Hospital had lesions that were deeper (p = 0.03) than those treated at St. Vincent Hospital. Survival differences were observed for patients with progesterone receptor-rich versus progesterone receptor-poor tumors (p = 0.004), grades 1 and 2 versus grade 3 lesions (p = 0.013), and malignant versus benign peritoneal cytologic results (p = 0.01). Differences in disease-free survival were observed for those patients with adnexal metastases versus those with no adnexal disease (p = 0.002), those with estrogen receptor-rich versus estrogen receptor-poor tumors, outer third myometrial invasion (p = 0.002), and patients with clinical stage I versus clinical stage II disease (p = 0.03). A stepwise Cox proportional hazards model was constructed to determine correlates of disease-free survival. In the final model, grade (p = 0.0002), peritoneal cytologic results (p = 0.0002), progesterone receptor status (p = 0.004), and age as a continuous variable (p = 0.008) were most closely associated with disease-free survival.