Utilization Efficiency of Human Milk Oligosaccharides by Human-Associated Akkermansia Is Strain Dependent.

Akkermansia muciniphila is a mucin-degrading bacterium found in the human gut and is often associated with positive human health. However, despite being detected by as early as 1 month of age, little is known about the role of Akkermansia in the infant gut. Human milk oligosaccharides (HMOs) are abundant components of human milk and are structurally similar to the oligosaccharides that comprise mucin, the preferred growth substrate of human-associated Akkermansia. A limited subset of intestinal bacteria has been shown to grow well on HMOs and mucin. We therefore examined the ability of genomically diverse strains of Akkermansia to grow on HMOs. First, we screened 85 genomes representing the four known Akkermansia phylogroups to examine their metabolic potential to degrade HMOs. Furthermore, we examined the ability of representative isolates to grow on individual HMOs in a mucin background and analyzed the resulting metabolites. All Akkermansia genomes were equipped with an array of glycoside hydrolases associated with HMO deconstruction. Representative strains were all able to grow on HMOs with various efficiencies and growth yields. Strain CSUN-19, belonging to the AmIV phylogroup, grew to the highest level in the presence of fucosylated and sialylated HMOs. This activity may be partially related to the increased copy numbers and/or the enzyme activities of the α-fucosidases, α-sialidases, and ß-galactosidases. This study examines the utilization of individual purified HMOs by Akkermansia strains representing all known phylogroups. Further studies are required to examine how HMO ingestion influences gut microbial ecology in infants harboring different Akkermansia phylogroups. IMPORTANCE Human milk oligosaccharides (HMOs) are the third most abundant component of breast milk and provide several benefits to developing infants, including the recruitment of beneficial bacteria to the human gut. Akkermansia strains are largely considered beneficial bacteria and have been detected in colostrum, breast milk, and young infants. A. muciniphila MucT, belonging to the AmI phylogroup, contributes to the HMO deconstruction capacity of the infant. Here, using phylogenomics, we examined the genomic capacities of four Akkermansia phylogroups to deconstruct HMOs. Indeed, each phylogroup contained differences in their genomic capacities to deconstruct HMOs, and representative strains of each phylogroup were able to grow using HMOs. These Akkermansia-HMO interactions potentially influence gut microbial ecology in early life, a critical time for the development of the gut microbiome and infant health.

Efficacy of electronic cigarettes for smoking cessation.

OBJECTIVE: To review data demonstrating effective smoking cessation with electronic cigarettes (e-cigarettes). DATA SOURCES: A literature search of MEDLINE/PubMed (1946-March 2014) was performed using the search terms e-cigarettes, electronic cigarettes, and smoking cessation. Additional references were identified from a review of literature citations. STUDY SELECTION AND DATA EXTRACTION: All English-language clinical studies assessing efficacy of e-cigarettes compared with baseline, placebo, or other pharmacological methods to aid in withdrawal symptoms, smoking reduction, or cessation were evaluated. DATA SYNTHESIS: A total of 6 clinical studies were included in the review. In small studies, e-cigarettes significantly decreased desire to smoke, number of cigarettes smoked per day, and exhaled carbon monoxide levels. Symptoms of nicotine withdrawal and adverse effects were variable. The most common adverse effects were nausea, headache, cough, and mouth/throat irritation. Compared with nicotine patches, e-cigarettes were associated with fewer adverse effects and higher adherence. Most studies showed a significant decrease in cigarette use acutely; however, long-term cessation was not sustained at 6 months. CONCLUSIONS: There is limited evidence for the effectiveness of e-cigarettes in smoking cessation; however, there may be a place in therapy to help modify smoking habits or reduce the number of cigarettes smoked. Studies available provided different administration patterns such as use while smoking, instead of smoking, or as needed. Short-term studies reviewed were small and did not necessarily evaluate cessation with a focus on parameters associated with cessation withdrawal symptoms. Though long-term safety is unknown, concerns regarding increased poisoning exposures among adults in comparison with cigarettes are alarming.

A novel high-titer, bifunctional lentiviral vector for autologous hematopoietic stem cell gene therapy of sickle cell disease.

A major limitation of gene therapy for sickle cell disease (SCD) is the availability and access to a potentially curative one-time treatment, due to high treatment costs. We have developed a high-titer bifunctional lentiviral vector (LVV) in a vector backbone that has reduced size, high vector yields, and efficient gene transfer to human CD34+ hematopoietic stem and progenitor cells (HSPCs). This LVV contains locus control region cores expressing an anti-sickling ßAS3-globin gene and two microRNA-adapted short hairpin RNA simultaneously targeting BCL11A and ZNF410 transcripts to maximally induce fetal hemoglobin (HbF) expression. This LVV induces high levels of anti-sickling hemoglobins (HbAAS3 + HbF), while concurrently decreasing sickle hemoglobin (HbS). The decrease in HbS and increased anti-sickling hemoglobin impedes deoxygenated HbS polymerization and red blood cell sickling at low vector copy per cell in transduced SCD patient CD34+ cells differentiated into erythrocytes. The dual alterations in red cell hemoglobins ameliorated the SCD phenotype in the SCD Berkeley mouse model in vivo. With high titer and enhanced transduction of HSPC at a low multiplicity of infection, this LVV will increase the number of patient doses of vector from production lots to decrease costs and help improve accessibility to gene therapy for SCD.

Improving pharmacist knowledge of oral chemotherapy in the community.

BACKGROUND: Approximately 10% of chemotherapy agents are administered orally, with anticipated annual growth of this practice. In the future, community pharmacy practitioners will potentially serve a larger role in the management of patients with cancer. OBJECTIVE: To improve pharmacist confidence, knowledge of oral chemotherapy agents, and dispensing behaviors through live continuing pharmacy education (CPE) programs. METHODS: A prospective cohort study of pharmacists attending live CPE programs in Rhode Island and Maine was conducted between March and May 2010. A survey was administered before and after the educational program; primary outcome measures included change in level of pharmacist confidence in oral chemotherapy knowledge, overall knowledge, and willingness to adjust behavior when dispensing oral chemotherapy agents in community pharmacy. RESULTS: Two hundred fifty-seven of the 410 pharmacists in attendance participated in the survey. Pharmacists significantly improved in confidence level, from no confidence to some confidence (p < 0.001). Counseling the family on the safe handling of oral chemotherapy increased from 37.1% pre-CPE program to 100% post-CPE program. Following the CPE program, behaviors such as (1) using a separate counting tray, (2) wearing gloves, and (3) requiring a double-check improved from 22.5%, 31.5%, and 29.4% baseline to 92.0%, 81.3%, and 81.8%, respectively. All responses to knowledge-based questions improved significantly. CONCLUSIONS: A live CPE program on oral chemotherapy designed to improve pharmacist confidence and knowledge, as well as inform about behaviors, is an effective method. Additional education to improve the knowledge of community-based practitioners to safely dispense and properly counsel patients receiving oral chemotherapy is required.

Pharmacy availability of emergency contraception in southwestern Pennsylvania: A simulated patient study.

OBJECTIVE: To assess the availability of oral emergency contraception in southwestern Pennsylvania pharmacies. STUDY DESIGN: We conducted a simulated patient study to assess on-the-shelf availability of levonorgestrel emergency contraception and immediate availability of ulipristal acetate emergency contraception. RESULTS: Only 44% of pharmacies stocked levonorgestrel on-the-shelf and only 5% of pharmacies had ulipristal acetate immediately available. CONCLUSIONS: We found significant barriers to obtaining timely oral emergency contraception in southwestern Pennsylvania. IMPLICATIONS STATEMENT: Timely access to emergency contraception is important for people's ability to determine if, when, how, and under what circumstances to have children. Pharmacies in southwestern Pennsylvania need to expand access to oral emergency contraception.

A microbiological survey of bicarbonate-based replacement circuits in continuous veno-venous hemofiltration.

OBJECTIVE: The potential for clinically significant transfer of pyrogen-inducing material in dialysate and substitution fluids is well recognized in the setting of chronic hemodialysis and hemodiafiltration and has led to the establishment of strict standards for microbiological purity. Preliminary evidence has indicated the potential for fluid contamination in continuous renal replacement therapy, and although the scale of the problem in contemporary, industry-standard equipment is unclear. We aimed to define the microbial integrity of modern continuous veno-venous hemofiltration (CVVH) replacement fluid circuitry. DESIGN: Twenty-four CVVH replacement fluid circuits (mean lifespan, 34.2 hours; range, 4-86) were studied at completion of therapy. SETTING: The integrated critical care unit and cardiothoracic intensive care unit of the Freeman Hospital, Newcastle upon Tyne, United Kingdom, between January and August 2007. SUBJECTS: Patients with renal failure receiving treatment with CVVH. INTERVENTIONS: Nil. MEASUREMENTS: Culture and endotoxin assays of replacement fluid, culture of endoluminal swabs, and electron microscopy of harvested tubing. MAIN RESULTS: Of the 24 replacement fluid cultures, nine (mean lifespan 32.8 hours, range 5-79) breached European Pharmacopoeia standards for ultrapure water (<0.1 colony-forming units/mL). One of 24 endotoxin measurements breached European Pharmacopoeia standards (<0.03 endotoxin units/mL). Internal tubing cultures were negative, but electron microscopy revealed 13 of the 24 collected tubing samples to be contaminated with biofilm. Only seven of the 24 studied circuits proved to be free from microbial contamination. CONCLUSIONS: We have confirmed frequent breaches of microbial integrity in industry-standard, bicarbonate-based CVVH, indicating the potential for added risk to the vulnerable, critically ill patient. These findings are of particular concern given the need for systemic infusion of replacement fluid. Measures to reduce the levels of contamination and their impact are discussed.

The Effect of a Student Pharmacist Directed Health-Education Program for Elementary-School Children.

OBJECTIVE: The primary objective of this study was to measure the effect of an annual student pharmacist led elementary-school health education program by assessing children's comprehension of educational sessions. Secondary objectives were to evaluate student pharmacists' knowledge of health-related topics and practice skills. METHODS: Student pharmacists led interactive learning sessions for elementary school students on nutrition, physical activity, summer safety, hygiene, medication safety, and tobacco prevention. Pre- and post-intervention surveys were administered to measure change in knowledge of health promotion and healthy lifestyles. Student pharmacists also completed pre- and post-health education intervention surveys to measure change in self-perception of knowledge, confidence, and practice application of health-related topics and practice skills. RESULTS: Three-hundred and four elementary school children participated in the study with significant knowledge improvements observed in medication safety and tobacco prevention. Twenty-five student pharmacists completed surveys, resulting in a collective self-improvement in each area measured. CONCLUSION: Interactive educational sessions led by student pharmacists have a positive impact on elementary school children's knowledge. Student pharmacists also demonstrated professional growth through increased knowledge, confidence, and communication skills in interacting with pediatric populations. PRACTICE IMPLICATION: A co-curricular educational activity allowed student pharmacists to promote health and wellness to elementary students, a Healthy People 2020 goal, while also providing an opportunity to develop professional skills for future practice with pediatric patients.

Primary care scribes: writing a new story for safety net clinics.

The spread of electronic health records systems (EHRs) poses challenges for both patient and provider care experience. Limited research suggests that scribes offer potential benefits to productivity and clinician satisfaction in emergency health and specialty settings. We conducted this evaluation of trained volunteer scribes for primary care clinics serving a diverse, low-income population in a US safety net system, which implemented a new EHR 2011-2014. The scribe programme trained and managed scribes for 51 providers (25% participation) from 5 of 12 San Francisco Health Network primary care clinics. We evaluated the programme using four measures. Providers reported spending less time out of clinic completing notes after sessions with scribes versus sessions without scribes (14.0 min vs 30.2 min, p<0.01). The rate of incomplete EHR notes at 72 hours was not significantly different for clinics using and not using scribes (16.9% vs 16.7%, p=0.4). Mean visit length using EHR-recorded provider cycle time was shorter for sessions with scribes (24.0 min), compared with sessions without scribes (26.4 min, p<0.01). Patients at clinics using scribes were as likely to recommend their provider (74.5%), compared with patients at clinics not using scribes (74.3%). Limitations of our evaluation include selection bias and possible confounding by clinic- and provider-level factors. In a safety net primary care system, trained volunteer scribes were associated with improved clinician efficiency and experience and no difference in patient satisfaction.

Availability and Accuracy of Information Regarding Nonprescription Emergency Contraception.

BACKGROUND: Although access to emergency contraception (EC) has increased with nonprescription status and approval of Plan B One-Step without age restrictions, barriers may still remain in patient education. This study assesses product availability and accuracy of information for EC among community pharmacies in Rhode Island, comparing changes from 2009 to 2012. METHODS: Two female investigators posing as patients seeking EC followed a standardized script over telephone conversations. Investigators assessed EC availability, product use information, and cost at all community (retail) pharmacies in Rhode Island. Data were reported as group results with no identifiers. Chi-square and Fisher exact tests were used to analyze results. RESULTS: During spring of 2009 and 2012, 165 and 171 pharmacies were telephoned, respectively. Approximately 90% of pharmacies stocked EC both years. In all, 62% versus 28% (P < .001) indicated EC should be taken as soon as possible; 82.5% versus 87.7% (P = .220) provided correct administration information; 67% versus 84% (P < .001) warned about adverse effects; and 67% versus 53% (P = .123) provided the correct minimum age for purchase. CONCLUSIONS: Access to nonprescription EC in Rhode Island is very good. Sites not stocking EC should reassess plans for patients to obtain medication. There is need for reeducation on EC labeling to improve counseling provided over the telephone.

Evolution of self-care education.

During the past 15 years, the curriculum content for nonprescription medication and self-care therapeutics has expanded significantly. Self-care courses ranging from stand-alone, required courses to therapeutic content and skills laboratories, have evolved in colleges and schools of pharmacy to accommodate rapid changes related to nonprescription medications and to meet the needs of students. The design of and content delivery methods used in self-care courses vary among institutions. Teaching innovations such as team-based learning, role playing/vignettes, videos, and social media, as well as interdisciplinary learning have enhanced delivery of this content. Given that faculty members train future pharmacists, they should be familiar with the new paradigms of Nonprescription Safe Use Regulatory Expansion (NSURE) Initiative, nonprescription medications for chronic diseases, and the growing trends of health and wellness in advancing patient-care initiatives. This paper reviews the significant changes that may be impacting self-care curriculums in the United States.

Integrating virtual patients into a self-care course.

OBJECTIVE: To develop, implement, and evaluate the use of virtual patients as a teaching tool for third-professional year PharmD students within an advanced elective self-care course. DESIGN: Practicing community pharmacists, faculty members, and pharmacy residents with alias e-mail accounts served as virtual patients and corresponded on a weekly basis via e-mail with pharmacy students regarding an assortment of fictional health concerns. Self-care inquiries were e-mailed to the students who replied and then forwarded their response to the course coordinator for evaluation and class discussion. At the end of the course, students were asked to assess the value of the learning activity. ASSESSMENT: Students demonstrated significant improvement in knowledge, problem-solving, communication, and professional skills upon course completion. Student's assessments of the virtual patient activity have suggested positive feedback on developing self-care skills, patient interactions, and group dynamics. CONCLUSION: This teaching tool was designed to enhance student's knowledge base, assessment, and counseling skills when interacting with patients in various situations. Instructor evaluation of responses, student feedback, and self-evaluation indicated the activity improved overall knowledge and communication skills.

Intermittent visceral edema induced by long-term enalapril administration.

OBJECTIVE: To describe a case of intermittent visceral angioedema associated with long-term enalapril use. CASE SUMMARY: A 72-year-old white woman developed severe abdominal pain as a result of visceral angioedema associated with long-term enalapril therapy. She had been taking enalapril 20 mg/day for 9 years prior to the first reported episodes of abdominal pain. DISCUSSION: Visceral angioedema associated with angiotensin-converting enzyme (ACE) inhibitors is a documented adverse effect. However, onset of symptoms has never been reported after 9 years of use. Not until 2 years after initial presentation were the symptoms correlated to enalapril administration. Since discontinuation of enalapril, the patient has not reported any symptoms for >2 years. An objective causality assessment categorized this adverse drug event as a result of enalapril as possible. CONCLUSIONS: Development of angioedema from ACE inhibitors occurs in <1% of the population. Limited case reports have identified intermittent visceral angioedema from ACE inhibitors. However, it is important to recognize that this adverse effect can also occur in patients who have been treated with ACE inhibitor therapy for several years.