Ease of use of two autoinjectors in patients with multiple sclerosis treated with interferon beta-1a subcutaneously three times weekly: results of the randomized,crossover REDEFINE study

Background: For interferon beta-1a subcutaneously three times weekly (IFN β-1a SC tiw), administration options include manually injected prefilled syringes; a preassembled, single-use autoinjector; and a reusable autoinjector. This study evaluated patient-perceived ease of use of two injection devices.

Research design and methods: REDEFINE, a Phase IV, multicenter crossover study, randomized patients with multiple sclerosis and ≥5 weeks’ IFN β-1a 44 μg SC tiw use to 4 weeks using a single-use autoinjector, then 4 weeks using a reusable autoinjector, or vice versa. The primary endpoint was the proportion rating each ‘easy’ or ‘very easy’, with/without regard to previous device experience.

Results: Of 97 randomized patients, 29 had most recent experience with manual injection; 23 with single-use autoinjector; and 45 with reusable autoinjector. 68.4% found using the single-use autoinjector very easy or easy, versus 77.9% for the reusable device (difference ?9.5%; p = 0.200). 40.0% versus 29.5% found the respective devices very easy (difference 10.5%; p = 0.203).

Conclusions: Most patients found both autoinjectors easy or very easy to use. Having two viable options may help accommodate patient preferences. Ease of administration and patient satisfaction relates to adherence; satisfied patients may more likely be adherent.

Trial registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT02019550).     

Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia is characterized by moderate thrombocytopenia and thrombotic complications, whereas quinine/quinidine-induced thrombocytopenia usually presents with severe thrombocytopenia and bleeding. Using flow cytometry and assays of procoagulant activity, we investigated whether sera from patients with these immune drug reactions could stimulate normal platelets to generate platelet-derived microparticles with procoagulant activity. Sera or purified IgG from patients with heparin-induced thrombocytopenia stimulated the formation of platelet-derived microparticles in a heparin-dependent fashion. Further studies showed that heparin-induced thrombocytopenia sera also produced a marked increase in procoagulant activity. In contrast, sera from patients with quinine- or quinidine-induced thrombocytopenia did not generate platelet-derived microparticles nor generate increased procoagulant activity. However, quinine/quinidine-induced thrombocytopenia sera produced a significant increase in the binding of IgG to platelets in a drug-dependent fashion, whereas sera from patients with heparin-induced thrombocytopenia demonstrated no drug-dependent binding of IgG to platelets. We also observed increased levels of circulating microparticles in patients with acute heparin-induced thrombocytopenia compared with control patients. Our observations indicate that the generation of procoagulant platelet-derived microparticles in vivo is a plausible explanation for the thrombotic complications observed in some patients with heparin-induced thrombocytopenia.     

What effect does increasing inpatient time have on outpatient-oriented internist satisfaction?

OBJECTIVE: Because career satisfaction among general internists is relatively low, we sought to understand the impact on satisfaction of general internists managing patients both in and outside of the hospital. Using data from a national survey, we asked, “Among outpatient-oriented general internists (i.e., internists who spend less than 50% of their clinical time caring for inpatients), what effect does time spent in the hospital have on physician satisfaction, stress, and burnout?” DESIGN/PARTICIPANTS: The Physician Worklife Study, in which 5,704 physicians in primary and specialty nonsurgical care selected from the American Medical Association’s Masterfile were surveyed (adjusted response rate=52%), was used. Our analyses focused on clinically active outpatient-oriented general internists (N=339). MEASUREMENTS AND MAIN RESULTS: We constructed multivariate linear models to test for statistically significant associations between the amount of time spent seeing inpatients and physician satisfaction as measured by several satisfaction scales. Even after controlling for total hours worked and other possible confounding variables, we found that increased time working in the hospital was significantly associated with decreases in satisfaction with administration, specialty, autonomy, and personal time, and significantly associated with an increase in life stress. There was also a significant association between increased time spent in the hospital and burnout. CONCLUSIONS: Our findings imply that there may be a tension between the practice of inpatient and outpatient medicine by general internists, and suggest that fewer hospital duties may increase career satisfaction for outpatient-oriented internists. Although additional studies are warranted in order to better understand why these relationships exist, our data suggest that the hospitalist model of inpatient care might be one approach to alleviate stress and improve satisfaction for many general internists.     

Supraoptic neurons in the rat hypothalamo-neurohypophysial explant: double-labeling with Lucifer Yellow injection and immunocytochemical identification of vasopressin- and neurophysin-containing neuroendocrine cells

By combining intracellular electrophysiology with double-labeled intracellular dye-marking and immunocytochemical identification of the same magnocellular neuroendocrine cell, we studied supraoptic neurons in the rat hypothalamo-neurohypophysial explant in vitro. This report examines neurophysiological and light microscopical features of vasopressin- and neurophysin-immunoreactive, pituitary-projecting supraoptic neurons.     

Training enhances vascular relaxation after chemotherapy-induced vasoconstriction

PURPOSE: Although evidence is accumulating that suggests regular moderate physical activity improves physiological and psychological well-being of cancer patients undergoing chemotherapy, the mechanisms involved remain unclear. Therefore, the purpose of this study was to determine if exercise training improves endothelium-dependent vasodilation after exposure to the chemotherapeutic agent 5-fluorouracil (5-FU). METHODS: Rats were injected with N-methyl-N-nitrosourea (MNU) and assigned to either exercise (EX; treadmill running, 20-25 m.min(-1) grade, 30 min.d(-1), 5 d.wk(-1) for 8 wk) or sedentary (SED) groups. After the exercise training period, aortic rings were obtained and used to assess contractile and relaxation characteristics. In addition, endothelial nitric oxide synthase (eNOS) protein content and eNOS enzyme activity was determined. RESULTS: Exercise training resulted in increased maximal endothelium-dependent vasorelaxation to acetylcholine (ACh, 1 x 10(-5) M) (SED, 56 +/- 3%; exercise, 71 +/- 5%; P < 0.05) after norepinephrine-induced (1 x 10(-7) M) vasoconstriction. Exposure of aortic rings from each group to increasing concentrations of 5-FU (7 x 10(-5) x 10 M(-3)) resulted in vasoconstriction. Rings obtained from exercise-trained animals demonstrated enhanced vasorelaxation to ACh (1 x 10(-5) M) after 5-FU-induced vasoconstriction compared with rings obtained from SED animals (P < 0.05). In addition, exercise training enhanced eNOS protein content and eNOS activity. CONCLUSION: Exercise training enhances endothelium-dependent vasorelaxation after 5-FU-induced vasoconstriction, and this may be due, at least in part, to an increase in aortic eNOS protein content and activity. Such exercise-induced adaptations may help alleviate chemotherapy-related fatigue observed in cancer patients.