2017 Meeting of the National Directors of Graduate Studies in Pharmacology and Physiology.

The National Directors of Graduate Studies biennial meeting is a forum for directors from pharmacology and physiology graduate programs to discuss challenges and best practices for programs that are preparing trainees to be successful in the biomedical workforce. The 2017 meeting was held on the campus of Stony Brook University in Stony Brook, NY. Over the course of the 3-day event, several themes evolved, including graduate education training and curricula, diversity and career development, and scientific rigor and communication. Overall, presentations and discussions highlighted the challenges and opportunities for training PhD biomedical scientists and featured best practices from across the country.

Medication safety curriculum: enhancing skills and changing behaviors.

BACKGROUND: Adverse drug reactions are a leading cause of death in the United States. Safe and effective management of complex medication regimens is a skill for which recent medical school graduates may be unprepared when they transition to residency. We wished to assess the impact of a medication safety curriculum on student competency when evaluating medication therapeutic appropriateness as well as evaluate students' ability to transfer curricular material to management of patients in clinical settings. METHODS: To prepare 3rd and 4th year medical students to critically evaluate medication safety and appropriateness, we developed a medication reconciliation/optimization curriculum and embedded it within a Patient-Centered Medical Home longitudinal elective. This curriculum is comprised of a medication reconciliation workshop, in-class and individual case-based assignments, and authentic patient encounters in which medication management skills are practiced and refined. Pre- and post-course competency and skills with medication reconciliation/optimization are evaluated by assessing student ability to identify and resolve medication-related problems (MRPs) in case-based assignments using paired difference tests. A group of students who had wished to enroll in the elective but whose schedule did not permit it, served as a comparison group. RESULTS: Students completing the curriculum (n = 45) identified 75 % more MRPs in case assignments compared to baseline. No changes from baseline were apparent in the comparison group. Enrolled students were able to transfer their skills to the care of authentic patients; these students identified an average of 2.5 MRPs per patient from a panel of individuals that had recently transitioned from hospital to home. Moreover, patient questionnaires (before and several months following the medication encounters with assigned students) indicated that patients felt more knowledgeable about several medication parameters as a result of the student-led medication encounter. Patients also indicated that students helped them overcome barriers to medication adherence (e.g. cost, transportation, side effects). CONCLUSIONS: Novice learners may have difficulty transitioning from knowledge of basic pharmacology facts to application of that information in clinical practice. Our curriculum appears to bridge that gap in ways that may positively impact patient care.

Bacillus coagulans GBI-30, 6086 limits the recurrence of Clostridium difficile-Induced colitis following vancomycin withdrawal in mice.

BACKGROUND: Recently, we found that the probiotic strain Bacillus coagulans GBI-30, 6086 (GanedenBC30) improved indices of Clostridium difficile (C. difficile)-induced colitis in mice (Fitzpatrick et al., Gut Pathogens, 2011). Our goal was to determine if BC30 could also prevent the recurrence of C. difficile-induced colitis in mice, following initial treatment with vancomycin. During study days 0 through 5, mice were treated with antibiotics. On day 6, the C. difficile strain VPI 10463 was given by oro-gastric gavage at ≈ 5x104 CFU to induce colitis. Mice were treated on study days 6 to 10 with vancomycin (50 mg/kg) (vanco) or vehicle (saline) by gavage. On days 10 to16, mice were dosed by gavage with saline vehicle or BC30 (2 x 109 CFU per day). Mice were monitored for mortality, weight loss and diarrhea. On study days 14, 16 and 17, stools and colons were collected for analyzing other parameters of colitis. RESULTS: The mean stool consistency score in Vehicle/C.difficile/Vanco mice increased from 0.4 (day 10) to a range of 1.1 to 1.4 (days 14 to 17), indicating the recurrence of colitis. On days 13 through 17, the stool consistency scores for the vancomycin/BC30 mice were significantly lower (p< 0.05) than for the vancomycin/vehicle cohort of animals. On day 17, 88.9% of mice treated with BC30 had normal stools, while this value was 0% with vehicle treatment (p value = 0.0004). Colonic myeloperoxidase (Units/2 cm colon) was significantly (p < 0.05) reduced from 4.3 ± 0.7 (Vehicle/C.difficile/Vanco) to 2.6 ± 0.2 (BC30/C. Difficle/Vanco). The colonic histology score and Keratinocyte derived-chemokine level in the colon were also lower in BC30 treated mice. SUMMARY: In BC30-treated mice, there was evidence of better stool consistency, as well as improved biochemical and histological indices of colitis, following initial treatment of animals with vancomycin. CONCLUSION: BC30 limited the recurrence of CD-induced colitis following vancomycin withdrawal in mice.

Bacillus Coagulans GBI-30 (BC30) improves indices of Clostridium difficile-Induced colitis in mice.

BACKGROUND: Probiotics have beneficial effects in rodent models of Clostridium difficile (C. diffiicle)-induced colitis. The spore forming probiotic strain Bacillus Coagulans GBI-30, 6086 (BC30) has demonstrated anti-inflammatory and immune-modulating effects in vitro. Our goal was to determine if BC30 improved C. difficile-induced colitis in mice. Starting on study day 0, female C57BL/6 mice were dosed by oro-gastric gavage for 15 days with vehicle (saline) or BC30 (2 × 109 CFU per day). Mice in the C. difficile groups received an antibiotic mixture (study days 5 to 8 in the drinking water), and clindamycin (10 mg/kg, i.p., on study day 10). The C. difficile strain VPI 10463 was given by gavage at 104 CFU to induce colitis on day 11. On day 16, stools and colons were collected for further analyses. RESULTS: All mice treated with BC30 survived on study day 13, while two mice treated with vehicle did not survive. On day 12, a significant difference (p = 0.0002) in the percentage of mice with normal stools (66.7%) was found in the BC30/C. difficile group, as compared to the vehicle/C. diffcile group (13.0%). On study day 16, 23.8% of mice treated with BC30 had normal stools, while this value was 0% with vehicle treatment (p value = 0.0187). On this day, the stool consistency score for the BC30/C. difficile group (1.1 ± 0.2) was significantly lower (p < 0.05) than for the vehicle/C. difficile cohort (1.9 ± 0.2). BC30 modestly attenuated the colonic pathology (crypt damage, edema, leukocyte influx) that was present following C. difficile infection. Colonic MIP-2 chemokine contents (pg/2 cm colon) were: 10.2 ± 0.5 (vehicle/no C. difficile), 24.6 ± 9.5 (vehicle/C. difficile) and 16.3 ± 4.3 (BC30/C. difficle). CONCLUSION: The probiotic BC30 improved some parameters of C. difficile-induced colitis in mice. BC30 prolonged the survival of C. diffiicle infected mice. Particularly, this probiotic improved the stool consistency of mice, in this infectious colitis model.

Lactobacillus and bifidobacteria combinations: a strategy to reduce hospital-acquired Clostridium difficile diarrhea incidence and mortality.

Incidence and virulence of Clostridium difficile-associated disease (CDAD) is increasing, particularly in institutional settings. Morbidity, mortality, and costs associated with this condition are high. Broad-spectrum antibiotics have long been recognized as the primary risk factor for CDAD due to disruption of protective normal gastrointestinal flora. We suggest that administration of appropriate lactobacilli and bifidobacteria probiotics could be employed as a strategy to protect hospitalized patients from CDAD by normalizing disrupted gastrointestinal flora, resulting in fewer cases per admission. Routine use of probiotics within institutional settings may substantially decrease healthcare costs. To date, relatively little is known about the role of probiotics as a means of preventing initial CDAD diagnosis. Although two reports suggestive of benefits have been published, these studies have been either too under-powered to draw definitive conclusions or have employed such restrictive inclusion criteria that results are not generalizable to most hospitalized adults. Since CDAD is an opportunistic infection associated with disrupted gut flora, it is logical to employ a strategy that modulates gut flora as a preventative approach. Herein, we report pilot data that is strongly suggestive that bifidobacteria and lactobacilli combinations may be effective in preventing this hospital-acquired infection and possibly reducing severity when diagnosed. These data are generalizable to all hospital patients since few exclusion criteria were employed. Limitations to these data are acknowledged since the pilot was not conducted in a placebo-controlled manner. Although generalizable, lack of a placebo precludes a definitive answer in terms of efficacy that lactobacilli and bifidobacteria may provide in CDAD prevention. Given substantial morbidity, mortality, and healthcare costs associated with CDAD, appropriately-designed clinical trials are warranted.

Duloxetine pharmacology: profile of a dual monoamine modulator.

Dysregulation within central monoaminergic systems is believed to underlie the pathology of depression. Drugs that selectively inhibit the reuptake of central monoamines have been used clinically to alleviate symptoms of depressive illnesses. Duloxetine, a novel compound currently under investigation for the treatment of depression, binds selectively with high affinity to both norepinephrine (NE) and serotonin (5-HT) transporters and lacks affinity for monoamine receptors within the central nervous system. It has been suggested that dual inhibition of monoamine reuptake processes may offer advantages over other antidepressants currently in use. In preclinical studies, duloxetine mimics many physiologic effects of antidepressants. Consistent with other antidepressants, duloxetine, by acute administration, elevates extracellular monoamine levels, while by chronic administration it does not alter basal monoamine levels. Like the selective serotonin reuptake inhibitor, fluoxetine, by microiontophoretic application, duloxetine inhibits neuronal cell firing. However, in comparison with fluoxetine, duloxetine is a more potent serotonin reuptake inhibitor. Furthermore, in behavioral experiments, duloxetine attenuates immobility in forced swim tests in animal models of depression to a greater extent than several other commonly used antidepressants. In a six-week open label uncontrolled study, duloxetine was evaluated in patients with a history of depression. Duloxetine was effective in treating depression as determined by marked reduction in Hamilton Depression Rating scores. Adverse effects reported during duloxetine treatment were minor and similar to those of other antidepressants. In an eight-week multicenter, double-blind, placebo-controlled study in patients with a major depressive disorder, duloxetine was effective as an antidepressant, particularly in patients with greater symptom severity. Only limited data are available regarding the pharmacokinetic profile of duloxetine in humans, although a half-life of 10 to 15 h has been reported. Studies conducted in healthy human subjects confirm the preclinical profile of duloxetine as an inhibitor of 5-HT and NE reuptake. Taken together, existing data suggest that duloxetine is a novel and effective antidepressant.