Complex Issues Affecting Student Pharmacist Debt

It is time for colleges and schools of pharmacy to examine and confront the rising costs of pharmacy education and the increasing student loan debt borne by graduates. These phenomena likely result from a variety of complex factors. The academy should begin addressing these issues before pharmacy education becomes cost-prohibitive for future generations. This paper discusses some of the more salient drivers of cost and student debt load and offers suggestions that may help alleviate some of the financial pressures.     

Risk factors for transmission of Mycobacterium tuberculosis from HIV-infected tuberculosis patients, Botswana.

OBJECTIVE: To identify risk factors for transmission of Mycobacterium tuberculosis from patients with tuberculosis and human immunodeficiency virus (HIV) infection in Botswana. DESIGN: Transmission was studied in 210 children aged <10 years (contacts) of unknown HIV status exposed to 51 adults with tuberculosis (index cases), including 41/49 (83.7%) with HIV infection. METHODS: Data collected on index cases included demographics, clinical and social characteristics, sputum, HIV, and CD4 lymphocyte results. Tuberculin skin testing was performed on contacts, and their parent or guardian was interviewed. A positive test was defined as > or = 10 mm induration. Skin test results were compared with results obtained from a population survey of children of similar age from the same community. RESULTS: A positive skin test was found in 12.1% of exposed children compared with 6.2% in the community (P = 0.005). Of the infected children, 22 (78.6%) were contacts of a close female relative. The risk of transmission increased with the degree of sputum smear positivity for acid-fast bacilli among female index cases (10.8% if smear 0+, 9.3% if smear 1+,29.4% if smear 2+, 44% if smear 3+, P < 0.001). In multivariate analysis, severe immunodeficiency (CD4 lymphocyte count <200 cells/mm3) among HIV-infected index cases was protective against transmission (OR 0.08, 95%CI 0.01-0.5, P = 0.006). CONCLUSION: The intensity of exposure to tuberculosis patients and the degree of sputum smear positivity for acid-fast bacilli remain important risk factors for transmission of M. tuberculosis during the era of HIV. However, tuberculosis patients with advanced AIDS may be less infectious than patients in earlier stages of AIDS.     

Effect of the first day correction on systematic setup error reduction

Treatment simulation is usually performed with a conventional simulator using kV X-rays or with a computed tomography (CT) simulator before the treatment course begins. The purpose is to verify patient setup under the same conditions as for treatment planning. Systematic (preparation) setup errors can be introduced by this process. The purpose of this study is to characterize the setup errors using electronic portal image (EPI) analyses and to propose a method to reduce the systematic component by performing simulation and patient preparation on the treatment machine. In this study, the first four or five days EPIs were analyzed from a total of 533 prostate cancer patients who were simulated on conventional simulators. We characterized setup errors using four parameters: {M(microi), Sigma (microi), RMS(microi), sigma (sigmai)}, where microi and sigmai are individual patient mean and standard deviation, M, Sigma, and RMS are the mean, standard deviation, and root-mean-square of underlying variables (microi and sigmai). We have performed a simulation of removing systematic components by correcting the first day setup error. As a comparison, we also carried out a similar analyses for patients simulated on a CT simulator and patients treated on a linac with an on-board kV CT imaging system, although a limited number of patients were available in these two samples. We found that Sigma (/ui)=(2.6,3.4,2.4) mm, and RMS(sigmai)=(1.5,1.9,1.0) mm in lateral, anterior/posterior, and cranial/caudal directions, indicating that systematic errors are much larger than random errors. Strong correlations were found between measurement on the first day and microi, implying the first day's measurement is a good predictor for microi. The same parameters were also computed for days 2-4, with and without the first day correction. Without correction, M(microi)2-4=(0.7,1.6,-1.0) mm, and Sigma(microi)2-4=(2.6,3.5,2.4) mm. With correction, M(microi)2-4=(0.0,0.4,0.4) mm, much closer to zero, and Sigma(microi)2-4=(1.8,2.2, 1.2) mm, also much smaller. While the use of a CT simulator can reduce the systematic errors, the benefits of first day correction can still be observed, although at a smaller magnitude. Therefore, the systematic setup error can be significantly reduced if the patient is marked and fields are verified on the treatment machine on the first fraction, preferably with an on-board kV imaging system.     

East/West Visiting Scholars in Pediatric Anesthesia Program (ViSiPAP): Developing tomorrow’s pediatric anesthesia leaders

Promoting and retaining junior faculty are major challenges for many medical schools. High clinical workloads often limit time for scholarly projects and academic development, especially in anesthesiology. To address this, we created the East/West Visiting Scholars in Pediatric Anesthesia Program (ViSiPAP). The program's goal is to help “jumpstart” academic careers by providing opportunities for national exposure and recognition through invited lectures and collaborative opportunities. East/West ViSiPAP benefits the participating scholars, the home and hosting anesthesia departments, and pediatric anesthesia fellowship training programs. By fostering a sense of well‐being and inclusion in the pediatric anesthesia community, East/West ViSiPAP has the potential to increase job satisfaction, help faculty attain promotion, and reduce attrition. Faculty and trainees are exposed to new expertise and role models. Moreover, ViSiPAP provides opportunities for women and underrepresented in medicine faculty. This program can help develop today's junior faculty into tomorrow's leaders in pediatric anesthesia. We advocate for expanding the concept of ViSiPAP to other institutions in academic medicine.     

HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana

There are limited real-world mutational and virological outcomes data of treatment-experienced persons diagnosed with HIV-1 subtype C (HIV-1 C) who are failing Integrase Strand Transfer Inhibitor-based regimens. Requisition forms sent for HIV-1 genotypic resistance testing (GRT) between May 2015 and September 2019 were reviewed and participants experiencing virologic failure while on dolutegravir (DTG) or raltegravir (RAL) cART at sampling recruited. Sanger sequencing of the HIV-1 Pol gene was performed from residual plasma samples and drug resistance mutational (DRM) analysis performed using the Stanford University HIV drug resistance database. 40 HIV-1C integrase sequences were generated from 34 individuals, 24 of whom were on DTG cART, three on RAL cART and seven on an unknown (DTG or RAL)-anchored cART at time of GRT. 11/34 (32%) individuals had DRMs to DTG and other integrase inhibitors. 7/11 (64%) patients had exposure to a RAL-based cART at the time of sampling. Out of the 11 individuals with DRMs, one (9%) had 2-class, 6 (55%) had 3-class, and 4 (36%) had 4-class multidrug-resistant HIV-1C. 7/11 individuals (64%) are currently virologically suppressed. Of the four individuals not virologically suppressed, three had extensive DRMs involving 4-classes of ARV drugs and one individual has demised. Resistance to DTG occurs more often in patients exposed to RAL cART. Individuals with 4-class DRMs plus integrase T97 and E157Q mutations appear to have worse outcomes. There is a need for frequent VL monitoring and GRT amongst treatment-experienced HIV-1C diagnosed individuals.     

Change in imitation for object manipulation between 10 and 12 months of age

By the end of the first year, infants show dramatic increases in manual skill. In this study we tested one factor likely to contribute to this change: an increase in the capacity for observational learning, which may enable infants to learn new behaviors and practice ones that they already possess. Thus, we evaluated change in imitation between 10 and 12 months of age. Twelve 10‐month‐olds and twelve 12‐month‐old infants were shown different kinds of manual actions on a variety of objects; infants also manipulated objects during a free play control condition. Results indicated that older infants benefited more than younger ones in the Demonstration condition and that at both ages, infants performed the target action more quickly after observing a demonstration. We hypothesize that observational learning can help manual skill development by enabling infants to learn new actions and select and practice ones already in their skill set. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 52: 90–99, 2010     

Norchloro-fluoro-homoepibatidine (NCFHEB) - a promising radioligand for neuroimaging nicotinic acetylcholine receptors with PET.

Cholinergic neurotransmission depends on the integrity of nicotinic acetylcholine receptors (nAChRs), and impairment of both is characteristic for various neurodegenerative diseases. Visualization of specific receptor subtypes by positron emission tomography (PET) has potential to assist with diagnosis of such neurodegenerative diseases and with design of suitable therapeutic approaches. The goal of our study was to evaluate in vivo the potential of (18)F-labelled (+)- and (-)-norchloro-fluoro-homoepibatidine ([(18)F]NCFHEB) in comparison to 2-[(18)F]F-A-85380 as PET tracers. In the brains of NMRI mice, highest levels of radioactivity were detected at 20 min post-injection of (+)-[(18)F]NCFHEB, (-)-[(18)F]NCFHEB, and 2-F-[(18)F]-A-85380 (7.45, 5.60, and 3.2% ID/g tissue, respectively). No marked pharmacological adverse effects were observed at 25 mug NCFHEB/kg. Uptake studies in RBE4 cells and in situ perfusion studies suggest an interaction of epibatidine and NCFHEB with the carrier-mediated choline transport at the blood-brain barrier. The data indicate that (+)- and (-)-[(18)F]NCFHEB have potential for further development as PET tracers.     

A class of sterol 14-demethylase inhibitors as anti-Trypanosoma cruzi agents

Chronic infection with the protozoan parasite Trypanosoma cruzi is a major cause of morbidity and mortality in Latin America. Drug treatments for the associated illness, Chagas disease, are toxic and frequently unsuccessful. In a screening effort against the drug target protein farnesyltransferase, we identified a series of disubstituted imidazoles with highly potent anti-T. cruzi activity that apparently acted through a mechanism independent of protein farnesylation. Metabolic labeling studies of T. cruzi suggested that sterol biosynthesis was inhibited. Combined GC/MS analysis confirmed depletion of cellular sterols and suggested that the site of action was sterol 14-demethylase, a cytochrome P450 enzyme. Spectral studies with recombinant T. cruzi sterol 14-demethylase demonstrated that the compounds bind directly to this enzyme. Two of the compounds were well absorbed when given orally to mice, gave sustained plasma levels, and were well tolerated. The compounds were administered orally to mice with acute T. cruzi infection and caused dramatic decrease in parasitemia and led to 100% survival. These disubstituted imidazole compounds can be prepared by a relatively short synthetic route and represent a structural class with potent anti-T. cruzi activity.