Our findings do not support an association between low 25OHD levels and statin-induced myalgia or CK elevation.

Recent meta-analyses suggest an increased risk of acute myocardial infarction (AMI) in patients with type 2 diabetes mellitus (T2DM) treated with rosiglitazone. These meta-analyses have drawn considerable criticisms. Retrospective observational studies do not consistently support this association. The objective of this study was to compare rates of adverse cardiovascular outcomes in T2DM patients treated with rosiglitazone alone or combined with metformin or metformin alone. This retrospective study, using the health maintenance organization database, included patients who were dispensed rosiglitazone (alone or with metformin) for at least 6 months as follows: rosiglitazone alone (n = 745), rosiglitazone and metformin (n = 2753), and metformin alone (n = 11 938). Adverse cardiovascular outcomes were new diagnosis of AMI, acute coronary syndrome (ACS), coronary revascularization (CRV), congestive heart failure (CHF), and all-cause mortality. Mean on-treatment follow-up was 30 months. After adjustment for covariates found to be significant in univariate analyses, rosiglitazone was associated only with CHF (hazard ratio [HR] = 2.23; 95% confidence interval [CI]: 1.41-1.95) with no increase of risk for AMI (HR = 1.13; 95%CI: 0.60-2.12), ACS (HR = 0.85; 95% CI: 0.57-1.26), coronary revascularization (HR = 1.22; 95% CI:0.82-1.54), or all-cause mortality (HR = 1.15; 95% CI: 0.85-1.56). In this community-based cohort, 30 months of therapy with rosiglitazone treatment was associated with increased risk of CHF but was not associated with increased risk of AMI, ACS, coronary revascularization, or all-cause mortality.

Endoxifen, the most active metabolite of the prodrug tamoxifen, is produced by cytochrome P450 CYP2D6. Breast cancer patients treated with tamoxifen who have reduced CYP2D6 activity, related to either genetic variation or drug inhibition, may have inferior outcomes. To assess the effect of concomitant CYP2D6 inhibiting drug use on clinical outcomes of breast cancer patients treated with adjuvant tamoxifen. We conducted a retrospective database analysis. Women with non-metastatic estrogen receptor positive tumors who had completed adjuvant tamoxifen therapy for 2 years, without treatment with adjuvant aromatase inhibitors or early relapse, were included. Patients were classified as users of CYP2D6 inhibitors if they purchased strong CYP2D6 inhibiting drugs for ≥ 4 consecutive months during tamoxifen treatment. Tumors were classified as "high risk" if adjuvant chemotherapy was prescribed. Primary endpoint was disease free (DFS) and secondary endpoint was overall survival (OS). 902 patients treated with tamoxifen (median duration, 4.9 years) were followed for a median period of 5.9 years. Fifty-nine (6.5%) patients were users of CYP2D6 inhibitors (median duration, 23 months). DFS at 3 years (corresponding to 5 years after tamoxifen initiation) did not differ between users and non-users of CYP2D6 inhibiting drugs (92.7 vs. 93.0%, respectively; adjusted P = 0.44). OS at 3 years was lower in the patients using CYP2D6 inhibiting drugs: 89.4 vs. 93.8%, but after adjustment for age and comorbidities this difference was not significant (P = 0.20). Overall recurrence rates did not differ between users and non-users of CYP2D6 inhibiting drugs (11.8 vs. 19.0% respectively, P = 0.23). Concomitant prolonged therapy with strong CYP2D6 inhibiting drugs does not affect adversely DFS and recurrence rates in tamoxifen-treated early breast cancer patients.

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BackgroundModern drug therapy accounts for a major share of health expenditure and challenges public provider resources. The objective of our study was to compare drug expenditure trends for ten major drug classes over 16 years at Maccabi Healthcare Services (MHS), the 2nd largest healthcare organization in Israel.MethodsA retrospective analysis of drug expenditure per HMO beneficiary between the years 1998–2014. Trends in annual mean drug expenditures per MHS member were compared among 10 major drug classes.ResultsAverage annual drug expenditure per beneficiary increased during the study period from 429.56 to 474.32 in 2014 (10.4 %). Ten drug classes accounted for 58.0 % and 77.8 % of total drug cost in 1998 and 2014, respectively. The overall distribution of drug expenditure among drug classes differed significantly between 1998 and 2014 (p < 0.001), mainly due to the increase in expenditure for cancer drugs, from 6.8 % of total drug cost to 30.3 %. In contrast, expenditures for cardiovascular drugs decreased during the same period from 16.0 to 2.7 %. Moreover, the median annual increase in net drug costs per HMO member during 1998–2014 was largest for cancer drugs (NIS 6.18/year; IQR, 1.70–9.92/year), about two-fold that of immunosuppressants, the second fastest growing drug class (NIS 2.81; IQR, 0.58–7.43/year).ConclusionsThe continuous rise in anti-cancer drug expenditure puts a substantial burden on the medication budgets of public health organizations. Coordinated measures involving policy makers, physicians, and pharmaceutical companies will be required for efficient cost containment.