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Objective: To identify and summarize FDA's Adverse Event Reporting System (FAERS) cases of progressive multifocal leukoencephalopathy (PML) associated with biological and targeted cancer therapies (BTCT) that were approved between 2009 and 2015., Methods: FAERS was searched using each BTCT name as primary or secondary suspect drug and the adverse reaction of PML. Among BTCTs with >2 case reports of PML, proportional reporting ratios (PRR) and 95% confidence intervals (CI) were calculated., Results: Among 49 new BTCTs, 82 cases of PML were found for 16 drugs. Significant PRR signals were found among 7 (14.6%) BTCTs including: brentuximab (24.5, CI:14.8-40.6), ofatumumab (16.3, CI:9.6-27.4), alemtuzumab (9.9, CI:6.0-16.4), obinutuzumab (7.4, CI:2.4-22.8), ibrutinib (5.6 CI:3.0-10.5), belimumab (4.5 CI:2.3-9.0), and idelalisib (4.1, CI:1.3-12.6). Among the 82 cases with significant signals, confirmation of the diagnosis of PML using objective criteria was found in 56% of the cases. A limitation of FAERS data is that missing data are common., Conclusions: When using BTCTs, clinicians and patients consider the risk of PML versus the therapeutic benefit, particularly when used in combination with other drugs which may cause PML, such as rituximab. It is important to recognize that PML may occur in some conditions, such as chronic lymphocytic leukemia, regardless of drug therapy., Competing Interests: Declaration of Interest Funding was received by National Cancer institute, 1 RO1 CA165609-01A1. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Primary Objective: Evaluate the effects of a point-of-dispensing (POD) pharmaceutical care model on outcomes of self-monitored blood glucose (SMBG) results, SMBG frequency, and medication adherence rates for patients with diabetes., Secondary Objective: Measure the rate at which physicians implemented therapy recommendations made by community pharmacists., Design: 12-month, noncrossover, single-group trial., Setting: Two independent community pharmacies in Richmond, Va., Patients: 101 patients were initially identified as potential participants; of the 82 that elected to participate in the study, 62 (76%) completed the first 6 months and 52 (63%) completed the entire 12-month study period., Intervention: This pharmaceutical care program was integrated into the dispensing function: subjective and objective data related to diabetes care were gathered with each prescription refill. Recommendations were made to patients and their physicians., Main Outcome Measures: SMBG values and frequency at baseline, 6, and 12 months. Diabetic medication adherence rates for 1 year before and during participation were evaluated. Community pharmacist recommendations and implementation status were followed over the 12-month period., Results: Average morning blood glucose values (n = 27) decreased from 178.6 mg/dL to 159.3 mg/dL, from baseline to 6 months, respectively (p = .07). Blood glucose values (n = 23) at baseline and 12 months decreased from 179.0 mg/dL to 149.7 mg/dL, respectively (p < .05). There was no statistical difference in SMBG frequency. A diabetes medication adherence rate of 90% was maintained over the 12-month study period. Physicians implemented 15 of 20 (75%) recommendations., Conclusion: This model offers an effective and efficient mechanism for providing pharmaceutical care for patients with diabetes.

Objective: To determine the effects of the maximum recommended over-the-counter (OTC) cimetidine dosage on phenytoin concentrations in ambulatory seizure patients on long-term phenytoin therapy., Methods: Adults with seizure disorders requiring phenytoin therapy were recruited. Trough total phenytoin concentrations were measured initially and once weekly for six weeks. All assays were performed using Biotrack patient-side cartridges. After a two-week baseline period, patients took cimetidine 200 mg twice daily for two weeks. Toxicity was monitored via weekly neurologic examinations and midweek telephone surveys. Patients were asked to return to clinic weekly during a two-week cimetidine washout period., Results: Nine patients entered and completed the study. All but two patients took other anticonvulsants known to interact with phenytoin (carbamazepine, n = 5; phenobarbital, n = 2). No adverse effects or changes in seizure frequency were reported. Paired Student's t-tests revealed no significant difference between serum phenytoin concentrations before (12.3+/-3.2 mg/L [mean +/- SD]) and after (12.8+/-4.0 mg/L) two weeks on the OTC cimetidine regimen. No differences were noted in estimated pharmacokinetic parameters (maximum metabolic rate, Michaelis-Menten constant) for the same time periods (paired Student's t-test, p > 0.05). The Biotrack assay had an r2 = 0.7311 (p < 0.001, two-sided) when compared with TDx., Conclusions: It is possible that the lack of change in phenytoin concentrations was a result of the low daily dosage of cimetidine used or other factors related to the "real world" setting of the study. However, the potential for a serious drug interaction occurring in patients taking long-term oral phenytoin and OTC cimetidine appears to be small.

We evaluated the possibility that increased arteriolar tone in salt-sensitive hypertension could be partially due to an altered vascular responsiveness to oxygen and/or tissue metabolites. The microvasculature of the superfused spinotrapezius muscle was studied with fluorescence microscopy in Dahl salt-sensitive rats fed low (0.45%) or high (7%) salt diets for 4 weeks. High salt intake produced hypertension (mean arterial pressure = 162 +/- 5 mm Hg vs 130 +/- 4 mm Hg for low salt rats, p < 0.05), and increased vascular tone at the level of the arcade arterioles but not in the smaller transverse or distal arterioles. Arcade arteriole constriction induced by increasing superfusate oxygen content (from 0% to 10% O2) was 60% greater in hypertensive rats than in normotensive rats, whereas oxygen-dependent constriction of transverse and distal arterioles was similar in the two groups. The oxygen-induced reduction in capillary perfusion (the fraction of time during which flow was observed in each vessel) was also greater in hypertensive than in normotensive rats. Arcade arteriole dilation during 2 Hz muscle contraction was significantly greater in hypertensive than in normotensive rats, but there were no differences between groups in the dilation of any other vessel type or in the capillary flow increases accompanying 2 or 8 Hz contraction. These results suggest that a hyperresponsiveness to the actions of blood-borne or tissue oxygen could contribute to increased arcade arteriolar tone in the spinotrapezius muscle of Dahl rats with salt-induced hypertension. The enhanced dilation of arcade arterioles during muscle contraction also suggests a localized hyperresponsiveness to tissue metabolites in this form of hypertension.