Treatment intensification for patients with type 2 diabetes and poor glycaemic control.

AIMS: To identify the time to and patient characteristics associated with treatment intensification in patients with type 2 diabetes (T2D) and poor glycaemic control. METHODS: Using a large US insurance claims database, we conducted a retrospective cohort study among adult patients with T2D and glycated haemoglobin (HbA1c) ≥8% (index date) after ≥3 months of therapy including metformin. Patients were required to have continuous enrolment for at least 12 months before (baseline) and after index date, and no injectable antidiabetes medications. We defined treatment intensification as prescription fill for injectable or additional oral antidiabetic drugs (OADs). Cox modelling was performed to identify factors associated with time to treatment intensification. RESULTS: For the 11 525 patients meeting the inclusion criteria, the mean age at index date was 57 years, 40% were female and the mean index HbA1c was 9.1%. Overall, 37% of patients had their treatment intensified <6 months after, 11% had their treatment intensified 6-12 months after, and 52% did not have their treatment intensified <12 months after the index date. A higher index HbA1c was associated with early intensification [hazard ratio (HR) 1.18 for HbA1c ≥9 to <10% and HR 1.41 for HbA1c ≥10% compared with HbA1c ≥8 to <9%; p < 0.0001), and later line of therapy was associated with late intensification (HR 0.78 for metformin with one OAD and HR 0.68 for metformin with ≥2 OADs compared with metformin monotherapy; p < 0.0001). CONCLUSIONS: Fewer than half of patients with T2D and treatment failure received intensification within 12 months in a real-world US population. Factors associated with treatment inertia can be used to target clinical care for these patients.

Risk of cardiovascular adverse events from trastuzumab (Herceptin(®)) in elderly persons with breast cancer: a population-based study.

Randomized controlled trials have reported a 4-5 times increased risk of heart failure (HF) in breast cancer patients receiving trastuzumab (Herceptin (®) ) compared to patients who do not receive trastuzumab. However, data regarding the cardiac effects of trastuzumab on elderly patients treated in general practice remain very limited. Using the US surveillance, epidemiology, and end results (SEER)-Medicare database, we conducted a retrospective cohort study on the cardiac effects of trastuzumab use in all incident breast cancer patients diagnosed from 1998 to 2007 who were 66 years and older, had no prior recent claims for cardiomyopathy (CM) or HF, and were followed through 2009. We defined our outcome as the first CM/HF event after diagnosis. We performed Cox-proportional hazard models with propensity score adjustment to estimate CM/HF risk associated with trastuzumab use. A total of 6,829 out of 68,536 breast cancer patients (median age: 75) had an incident CM/HF event. Patients who received trastuzumab tended to be younger, non-white, diagnosed more recently, and had a stage IV diagnosis. Trastuzumab use was associated with an increased risk of CM/HF (HR = 2.08, 95 % CI 1.77-2.44, p < 0.001). The trastuzumab-associated CM/HF risk was stronger in patients who were younger (HR = 2.52 for 66-75 years and HR = 1.44 for 76 years and older, p < 0.001) and diagnosed in recent years (HR = 2.58 for 2006-2007 vs. 1.86 for 1998-2005, p = 0.01). The twofold risk of CM/HF associated with trastuzumab remained regardless of patients' diagnosis stage, presence of hypertension, cardiovascular comorbidities, or receipt of anthracyclines, taxanes, or radiation. Trastuzumab may double CM/HF risk among elderly breast cancer patients. Our findings reinforce the need to prevent and manage cardiac risk among elderly breast cancer patients receiving trastuzumab.

Bevacizumab use and risk of cardiovascular adverse events among elderly patients with colorectal cancer receiving chemotherapy: a population-based study.

BACKGROUND: Cardiovascular risk attributable to bevacizumab (Avastin(®), BEV) for treatment of metastatic colorectal cancer (CRC) remains unclear. We conducted a population-based cohort study to assess the safety of BEV use among patients aged ≥ 65. PATIENTS AND METHODS: We identified CRC patients diagnosed from 2005 to 2007 who received chemotherapy and were followed until 31 December 2009. Outcomes were 3-year risk of arterial thromboembolic events (ATEs), cardiomyopathy or congestive heart failure (CM/CHF), and cardiac death (CD) after chemotherapy initiation. We fitted Cox-proportional hazards (PHs) models with inverse-probability-of-treatment-weights and calculated hazard ratios (HRs) for the risk of adverse events. RESULTS: We identified 6803 CRC patients (median age: 73 years). Those with cardiac comorbidity were less likely to receive BEV (P < 0.0001). BEV is associated with an elevated risk of ATEs (HR = 1.82, 95% CI = 1.20-2.76, P < 0.001; rate difference: 3.5 additional cases/1000 person-years). We observed no association between BEV and CD or CM/CHF. CONCLUSIONS: In general practice, the cardiovascular risk of BEV in elderly CRC is modest. The observed ATEs risk is lower than reported in clinical trials, which may be due to careful patient selection. Our findings may facilitate clinical decision-making of BEV use in elderly patients.

Predicting preference-based SF-6D index scores from the SF-8 health survey.

PURPOSE: To develop and test functions for predicting the preference-based SF-6D index scores from the SF-8 health survey. METHODS: This study was a secondary analysis of data collected in a population health survey in which respondents (n = 7,529) completed both the SF-36 and the SF-8 questionnaires. We examined seven ordinary least-square estimators for their performance in predicting SF-6D scores from the SF-8 at both the individual and the group levels. RESULTS: In general, all functions performed similarly well in predicting SF-6D scores, and the predictions at the group level were better than predictions at the individual level. At the individual level, 42.5-51.5% of prediction errors were smaller than the minimally important difference (MID) of the SF-6D scores, depending on the function specifications, while almost all prediction errors of the tested functions were smaller than the MID of SF-6D at the group level. At both individual and group levels, the tested functions predicted lower than actual scores at the higher end of the SF-6D scale. CONCLUSIONS: Our study developed functions to generate preference-based SF-6D index scores from the SF-8 health survey, the first of its kind. Further research is needed to evaluate the performance and validity of the prediction functions.

Treatment intensification in patients with type 2 diabetes who failed metformin monotherapy.

AIM: To evaluate the time to and factors associated with treatment intensification in patients with type 2 diabetes who failed metformin monotherapy. METHODS: In a retrospective analysis using a large US electronic medical record database, eligible patients included those with type 2 diabetes and an HbA(1c) of ≥7.0% or at least two fasting blood glucose levels of ≥126 mg/dl while on metformin monotherapy for at least 6 months within the period of 1 January 1997 to 31 December 2008. Time to treatment intensification was calculated as the time between index date (date on which HbA(1c) ≥ 7% after metformin monotherapy for at least 6 months) and first prescription for additional antihyperglycaemic agent during follow-up period. All patients were required to have data for at least 12 months prior to and following the index date. A Cox proportional hazards model was employed to determine patient baseline characteristics associated with time to treatment intensification. RESULTS: Of the 12 566 patients identified, mean age at index date was 63 years and 51% were female. Mean index HbA(1c) was 8.0% overall, with 66, 19 and 15% of patients having an index HbA(1c) of 7 to <8%, 8 to <9% and ≥9%, respectively. Median time to treatment intensification was 14.0 months overall and 19.0, 8.7 and 4.5 months for patients with index HbA(1c) of 7 to <8%, 8 to <9% and ≥9%, respectively. Factors associated with treatment intensification included higher index HbA(1c) , younger age, higher Charlson co-morbidity index, metformin daily dose ≥ 1500 mg and later index date (all p < 0.05). CONCLUSIONS: In US clinical practice, median time to receive additional antihyperglycaemic medication is more than 1 year for patients with type 2 diabetes who failed metformin monotherapy.

Impact of concurrent macrovascular co-morbidities on healthcare utilization in patients with type 2 diabetes in Europe: a matched study.

AIM: To examine and to quantify the impact of concurrent macrovascular co-morbidities (MVC) on healthcare resource utilization among patients with type 2 diabetes mellitus (T2DM) in Europe. METHODS: This is a matched cohort study based on the Real-Life Effectiveness and Care Patterns of Diabetes Management study, a multicentre, observational study with retrospective medical chart reviews of T2DM patients in Spain, France, UK, Norway, Finland, Germany and Poland. Included patients were aged > or =30 years at time of diagnosis of T2DM who added a sulfonylurea or a PPARgamma agonist to failing metformin monotherapy (index date) and had concurrent MVC (cases). A control cohort with T2DM but without concurrent MVC was identified using 1:1 propensity score matching. Logit models were used to identify the relationship between concurrent MVC and the likelihood of emergency room admission, receiving medical/surgical procedures, and hospitalization during the study period after controlling for baseline demographics, clinical information and baseline treatment. Negative binomial models were used to predict the number of office visits and length of hospital stay per year attributable to the concurrent MVC. RESULTS: Relative to controls, patients with MVC were significantly more likely to have emergency department admissions [odds ratio (OR) 2.69; 95% CI: 1.56-4.65], receiving medical/surgical procedures (OR 2.57; 95% CI: 1.56-4.21) and hospitalizations (OR 2.58; 95% CI: 1.64-4.07) after controlling for other predictors. Similarly, MVC were associated with 1.49 additional office visits per year (p = 0.036) and 0.32 days of hospital stay per year (p = 0.023). CONCLUSIONS: Within a seven-country European sample, this study showed that T2DM patients with MVC were more likely to use healthcare resources compared with T2DM patients without MVC.

Using an automated recruitment process to generate an unbiased study sample of multiple sclerosis patients.

The objective of this study was to test the efficiency of an automated recruitment methodology developed as a component of a practical controlled trial to assess the benefits of a Web-based personal health site to guide self-management of multiple sclerosis symptoms called Mellen Center Care On-line. We describe the study's automated recruitment methodology using clinical and administrative databases and assess the comparability between subjects who completed informed consent (IC) forms, and individuals who were invited to participate but did not reply, designated as patient nonresponders (PNR). The IC and PNR groups were compared on demographics, number of physician or advanced practice nurse/physician assistant visits during the 12 months prior to the initial invitation, and level of disability as measured by the Charlson Comorbidity Index (CCI). Out of a total dynamic potential pool of 2,421 patients, 2,041 had been invited to participate, 309 had become ineligible to participate during the study, and 71 individuals remained in the pool at the end of recruitment. The IC group had a slightly greater proportion of females. Both groups were predominantly white with comparable marital status. The groups had comparable mean household income, education level, and commercial insurance. The computed mean CCI was similar between the groups. The only significant difference was that the PNR group had fewer clinic visits in the preceding 12 months. The subjects were highly representative of the target population, indicating that there was little bias in our selection process despite a constantly changing pool of eligible individuals.

Sequential purification of human apolipoprotein B-100, albumin, and fibrinogen by immunoaffinity chromatography for measurement of protein synthesis.

A determinant of the accuracy of protein synthesis measurement using stable isotope is the purity of the protein under study. An Immunoaffinity chromatographic technique to sequentially purify human plasma albumin, fibrinogen, and apolipoprotein B-100 (ApoB-100) was developed to measure isotopic enrichment in these proteins. The technique, utilizing immobilized mouse monoclonal antibodies specific to human plasma ApoB-100, albumin, and fibrinogen onto an affinity matrix, allowed purification of very low density lipoprotein (VLDL) ApoB-100, albumin, and fibrinogen from 1- to 2-ml plasma samples. Analytical sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by silver staining demonstrated consistent purity of the three purified proteins. The identity and the purity of the proteins separated by this technique were also confirmed by amino acid sequence analysis. This technique was applied to sequentially purify and measure the isotopic enrichment in those proteins by mass spectrometry from human plasma samples collected after orally ingesting L[1-13C]-leucine. Reproducibility of the enrichment measurements is within 5% of the coefficient of variation. Measurements [13C]leucine in these proteins purified from plasma samples collected during a 10-h primed continuous intravenous infusion of L-[1-13C]leucine confirmed that this technique provides an efficient way to purify plasma VLDL ApoB-100, albumin, and fibrinogen for measuring their synthetic rates in human metabolism studies.