Advancing our pharmacy reformation-accelerating education and practice transformation: Report of the 2019-2020 argus commission

© 2020, American Association of Colleges of Pharmacy. All rights reserved. The Argus Commission examined changes that should be considered by colleges and schools of pharmacy to meet the bold aim of better integrating pharmacists’ and physi-cians’ practices articulated by President Sorensen. The Commission assessed the readiness of pharmacy educators to contribute to the acceleration of practice transformation. The primary focus of the report is on how the doctor of pharmacy curriculum and post-graduate training might be modified and better aligned to ensure that graduates complete their education ready to engage in roles partnered with primary care clinicians. The aim is to achieve comprehensive medication management and other pharmacist patient care services as standards of care. The Argus Commission provides preliminary recommendations for new or more intensified priorities by the 2020-21 AACP Strategic Planning Committee as they update the AACP plan. This includes the recommendation that AACP should create the Center for Academic Innovation and Practice Transformation, a hub to coordinate many current and emerging activities relevant to accelerating change in pharmacy education and practice

TLR9 regulates Th1 responses and cooperates with TLR2 in mediating optimal resistance to Mycobacterium tuberculosis

To investigate the role of Toll-like receptor (TLR)9 in the immune response to mycobacteria as well as its cooperation with TLR2, a receptor known to be triggered by several major mycobacterial ligands, we analyzed the resistance of TLR9−/− as well as TLR2/9 double knockout mice to aerosol infection with Mycobacterium tuberculosis. Infected TLR9−/− but not TLR2−/− mice displayed defective mycobacteria-induced interleukin (IL)-12p40 and interferon (IFN)-γ responses in vivo, but in common with TLR2−/− animals, the TLR9−/− mice exhibited only minor reductions in acute resistance to low dose pathogen challenge. When compared with either of the single TLR-deficient animals, TLR2/9−/− mice displayed markedly enhanced susceptibility to infection in association with combined defects in proinflammatory cytokine production in vitro, IFN-γ recall responses ex vivo, and altered pulmonary pathology. Cooperation between TLR9 and TLR2 was also evident at the level of the in vitro response to live M. tuberculosis, where dendritic cells and macrophages from TLR2/9−/− mice exhibited a greater defect in IL-12 response than the equivalent cell populations from single TLR9-deficient animals. These findings reveal a previously unappreciated role for TLR9 in the host response to M. tuberculosis and illustrate TLR collaboration in host resistance to a major human pathogen

Translating Hemoglobin A1c Scores across an Ethnically Diverse Population: Is the Language Consistent across All Races?

Hemoglobin A1c testing is an accepted measure of how well the blood glucose level has been controlled in the recent past (six to eight weeks) among individuals with diabetes. The purpose of this study was to evaluate the relationship between hemoglobin A1c (HbA1c) and blood glucose in an ethnically diverse population in a clinical setting. A cross-sectional research design was employed to explore associations between these two diabetes control measures in a sample of African American, White and Hispanic patients receiving diabetes treatment and follow-up in an outpatient clinic in Tallahassee, Florida. Data collection included a questionnaire, medical examinations, and lab results. Although we found a significant association between the glucose level and the HbA1c levels, the A1c value did not predict the mean glucose value as closely as previously found in less diverse groups. These findings suggest there is need for further study of these two variables among minority groups

Measurement of Condensed Water Content in Liquid and Ice Clouds Using an Airborne Counterflow Virtual Impactor

Condensed water content (CWC) measured using a counterflow virtual impactor (CVI) with a Lyman-α hygrometer downstream is compared with that measured by other airborne instruments (a hot-wire probe, a PMS FSSP, and a PMS 2D-C). Results indicate that the CVI system provides a reliable measurement of CWC in both liquid- and ice-phase clouds and that the CVI measures CWC contained in both large and small hydrometeors; this means that the condensed water present in both phases and virtually all hydrometeor sizes can be measured with a single device. Small ice contents of a few milligrams per cubic meter present in cirrus clouds can also be measured by the technique

Timing and source of subtype-C HIV-1 superinfection in the newly infected partner of Zambian couples with disparate viruses

BACKGROUND: HIV-1 superinfection occurs at varying frequencies in different at risk populations. Though seroincidence is decreased, in the negative partner of HIV-discordant couples after joint testing and counseling in the Zambia Emory HIV Research Project (ZEHRP) cohort, the annual infection rate remains relatively high at 7-8%. Based on sequencing within the gp41 region of each partner's virus, 24% of new infections between 2004 and 2008 were the result of transmission from a non-spousal partner. Since these seroconvertors and their spouses have disparate epidemiologically-unlinked viruses, there is a risk of superinfection within the marriage. We have, therefore, investigated the incidence and viral origin of superinfection in these couples. RESULTS: Superinfection was detected by heteroduplex mobility assay (HMA), degenerate base counting of the gp41 sequence, or by phylogenetic analysis of the longitudinal sequences. It was confirmed by full-length env single genome amplification and phylogenetic analysis. In 22 couples (44 individuals), followed for up to five years, three of the newly infected (initially HIV uninfected) partners became superinfected. In each case superinfection occurred during the first 12 months following initial infection of the negative partner, and in each case the superinfecting virus was derived from a non-spousal partner. In addition, one probable case of intra-couple HIV-1 superinfection was observed in a chronically infected partner at the time of his seroconverting spouse's initial viremia. Extensive recombination within the env gene was observed following superinfection. CONCLUSIONS: In this subtype-C discordant couple cohort, superinfection, during the first year after HIV-1 infection of the previously negative partner, occurred at a rate similar to primary infection (13.6% [95% CI 5.2-34.8] vs 7.8% [7.1-8.6]). While limited intra-couple superinfection may in part reflect continued condom usage within couples, this and our lack of detecting newly superinfected individuals after one year of primary infection raise the possibility that immunological resistance to intra-subtype superinfection may develop over time in subtype C infected individuals

Headstrong intervention for pediatric migraine headache: a randomized clinical trial

Background The purpose of this study was to evaluate the efficacy of a self-guided CD-ROM program (“Headstrong”) containing cognitive-behavioral self-management strategies versus an educational CD-ROM program for treating headaches, headache-related disability, and quality of life. Methods Participants were 35 children ages 7–12 years with migraine recruited from one university medical center and two children’s hospital headache clinics. Participants were randomly assigned to complete the Headstrong or educational control CD-ROM program over a 4-week period. Data on headache frequency, duration, and severity, migraine-related disability, and quality of life (QOL) were obtained at baseline, post-intervention, and 3-months post-intervention. Results At post-intervention, Headstrong resulted in lower severity (on a 10-point scale) than the control group by child report (5.06 ± 1.50 SD vs. 6.25 ± 1.92 SD, p = 0.03, ES = 0.7). At 3-months post-intervention, parents reported less migraine-related disability (on the PedMIDAS) in the Headstrong group compared to the control group (1.36 ± 2.06 SD vs. 5.18 ± 6.40 SD; p = 0.04, ES = 0.8). There were no other group differences at post treatment or at 3-months post-intervention. Conclusions When compared to an educational control, Headstrong resulted in lower pain severity at post-treatment and less migraine-related disability at 3-months post-intervention, by child and parent report respectively. Headache frequency and quality of life did not change more for Headstrong versus control. Additional research is needed on the Headstrong Program to increase its efficacy and to test it with a larger sample recruited from multiple centers simultaneously.The study reported in this paper was funded by a grant from the National Institutes of Health, (National Institute of Neurological Disorders and Stroke), R01-NS046641, Michael Rapoff, Principal Investigator

VH1-69 Utilizing Antibodies Are Capable of Mediating Non-neutralizing Fc-Mediated Effector Functions Against the Transmitted/Founder gp120

Multiple antibody effector functions arise in HIV-1 infection that could be harnessed to protect against infection or clear the persistent reservoir. Here, we have investigated the genetic and functional memory B cell and antibody landscape present during early infection in six individuals infected with either subtype A, C, or an A/C recombinant HIV-1. These individuals demonstrated varying levels of plasma autologous neutralization (nAb) against the transmitted/founder envelope (T/F Env) pseudovirus and non-neutralizing Fc-mediated effector function (nnFc) antibody-dependent cell-mediated cytotoxicity (ADCC) against the T/F Env gp120 protein at ~7 months after infection. Genetic analysis of the immunoglobulin heavy (VH) and light (VL) chain variable domain gene segments from 352 autologous T/F Env gp120-specific single B cells recovered at this same 7-month time-point revealed an over-representation of the VH1-69 germline in five of six individuals. A defining feature of the VH1-69 utilizing gp120-specific antibodies was their significantly more hydrophobic complementarity-determining region-2 (CDRH2) regions compared to other VH CDRH2 sequences from each individual. While none of the VH1-69 antibodies possessed strong neutralizing activity against virions pseudotyped with the autologous T/F Env, almost a third were capable of mediating high ADCC activity, as assayed by intracellular granzyme B activity in CEM.NKr.CCR5 target cells coated with autologous T/F Env gp120. High ADCC mediating VH1-69 antibodies exhibited shorter complementarity-determining region-3 (CDRH3) lengths and a more neutral isoelectric point than antibodies lacking this function. In the individual that developed the highest autologous ADCC responses, the high granzyme B producing antibodies bound to surface expressed envelope in the absence of CD4 and were not enhanced by the addition of soluble CD4. Overall, VH1-69 utilizing antibodies are commonly induced against gp120 in diverse HIV-1 infections and a subset of these antibodies can mediate ADCC functions, serving as a bridge between the innate and adaptive immune response to HIV-1

Effect of Expanding the Earned Income Tax Credit to Americans without Dependent Children on Psychological Distress (Paycheck Plus): a Randomized Controlled Trial.

Anti-poverty policies have the potential to improve mental health. We conducted a randomized trial to investigate whether a fourfold increase in the Earned Income Tax Credit for low-income Americans without dependent children would reduce psychological distress relative to the current federal credit (Paycheck Plus, New York City site). Between 2013 and 2014, 5,968 participants were recruited; 2,997 were randomly assigned to the treatment group and 2,971 were assigned to the control group. Survey data were collected 32 months post-randomization (N=4,749). Eligibility for the program increased employment by 1.9 percentage points and after-bonus earnings by 6% ($635 per year) on average over the three years. Treatment was associated with a marginally statistically-significant decline in psychological distress relative to the control group (-0.30 points; 95% CI, -0.63 to 0.03; p=0.076). Women in the treated group experienced a half-a-point reduction in psychological distress (-0.55; 95% CI, -0.97 to -0.13; p=0.032) and noncustodial parents reported a 1.36 point reduction (95% CI, -2.24 to -0.49; p = 0.011) in psychological distress. An expansion of a large anti-poverty program to individuals without dependent children reduced psychological distress for women and noncustodial parents - the groups who benefitted the most in terms of increased after-bonus earnings