Sodium-Glucose Co-Transporter 2 Inhibitors and the Risk of Genitourinary Infections at HbA1c ≥10%: A Population Health-Based Retrospective Review.

BACKGROUND: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are first-line treatment for type 2 diabetes. Evidence has shown a 3- to 5-fold increase in the risk of genitourinary infections with their use due to inhibition of renal glucose reabsorption, resulting in glucosuria. Increased glucosuria is thought to increase the risk of genitourinary infections at a greater degree in patients with a significantly elevated HbA1c (≥10%), and initiation of SGLT2i is often delayed in these patients. While a limited body of evidence exists indicating that A1c level is not an independent risk factor for SGLT2i-induced genitourinary infection, pragmatically this concern remains a barrier to SGLT2i utilization. OBJECTIVE: Evaluate the real-world genitourinary (GU) infection rate in patients receiving SGLT2i with a baseline HbA1c ≥10% compared to patients with a baseline HbA1c <10%. METHODS: This retrospective cohort study evaluated data from 5542 adult patients treated between January 2013 and January 2023, who were prescribed an SGLT2i. Data collected included sex, age, race/ethnicity, renal function, date of SGLT2i start, number of SGLT2i orders, name and dose of SGLT2i, HbA1c, and a predetermined set of diagnosis codes related to bacterial and fungal genitourinary infections. The primary outcome was the overall GU infection rate after SGLT2i initiation within groups of baseline HbA1c of ≥10% and <10%, and the secondary outcome was total GU infections within these same groups. RESULTS: The primary outcome was equivalent between those with HbA1c <10% and HbA1c ≥10% (0.0064 ± 0.0565 vs 0.0030 ± 0.0303 infection per month [mean ± standard deviation]; P < 0.0001 for both lower and upper bounds). There was no statistically significant difference in total GU infections between the same groups (0.027 ± 0.21 vs 0.015 ± 0.14, P = 0.11). Female gender and prior recurrent infection were associated with increased GU infection after SGLT2i. CONCLUSION AND RELEVANCE: A baseline HbA1c ≥ 10% was not significantly associated with an increased risk of GU infection following the initiation of SGLT2i compared to those with a baseline HbA1c of <10%.

The Tokyo 2020 Olympic and Paralympic pharmacy services during the COVID-19 pandemic.

BACKGROUND: During the Tokyo 2020 Games, pharmacists were required to provide appropriate pharmacotherapeutic care to athletes and officials at the polyclinic. Owing to the worldwide COVID-19 pandemic that was prevalent at the Games, it was imperative to strengthen infection control measures in the setting of such a major sporting event and to prevent and minimize the spread of COVID-19. OBJECTIVE: This study reports on the COVID-19 infection control measures and services provided by the pharmacy at the Tokyo 2020 Games. By evaluating pharmacy operations that took place under the COVID-19 protocol, this study provides insights for the organization of future sporting events, specifically their medical facilities. METHODS: Infection control measures in the pharmacy were implemented in accordance with the manual for dealing with COVID-19 infections. The number and content of issued and dispensed prescriptions were obtained from the electronic medical records and pharmacy department systems. These data were compared with those of the London 2012 Games, which were used as a reference for the pharmacy operations at the Tokyo 2020 Games. RESULTS: The participating pharmacists were fully trained in infection control measures. The number of prescriptions issued during the Olympics and Paralympics were 1120 and 1022, respectively. Prescriptions issued at the fever clinic accounted for 4% of the total number (77/2142). No influenza antiviral medications were prescribed, though medications to alleviate cold-like symptoms were issued. Compared to the London 2012 Games, there was a decrease (-59%) in the number of prescriptions. CONCLUSION: The positive impact of COVID-19 infection control measures was evident. The volume of prescriptions at the Tokyo 2020 Games was lower than that at the London 2012 Games. It was inferred that this was due to thorough infection control measures as well as enhanced pre-entry medical checkups before entering Japan, which reduced the incidence of diseases.

[A Case of Unknown Primary Carcinoma with Dermatomyositis].

A 50-year-old woman was diagnosed with dermatomyositis at the department of neurology in our hospital; she then received steroid pulse therapy. A positron emission computed tomography(PET-CT)revealed swollen lymph nodes near the aorta and in the left inguinal region. She presented at our institution for examination to determine the cause of her lymphadenopathy, but the primary site of the carcinoma was unknown. A histopathological examination of the lymph node specimen obtained using endoscopic ultrasonography-guided fine-needle aspiration(EUS-FNA)revealed a moderately to poorly differentiated adenocarcinoma. The patient underwent lymphadenectomy. After the surgery, a new lymph node metastasis appeared in the lower abdomen. We initiated a combination treatment with chemotherapy and radiotherapy. The patient died because of disease progression 31 months after her first visit.

Plant chromium uptake and transport, physiological effects and recent advances in molecular investigations.

Increasingly, anthropogenic perturbations of the biosphere manifest in a broad array of global phenomena, causing widespread contamination of most ecosystems, with high dispersion rates of many contaminants throughout different environmental compartments, including metals. Chromium (Cr) contamination in particular, is, increasingly, posing a serious threat to the environment, emerging as a major health hazard to the biota. However, although the molecular and physiological mechanisms of plant responses to many heavy metals, especially lead (Pb) and cadmium (Cd), have been focused upon in recent years, chromium has attracted significantly less attention. In this context, this review discusses aspects of Cr uptake and transport, some physiological and biochemical effects of Cr exposure in plants, and molecular defense mechanisms against this metal. Recent advances in determining these responses, in fields of knowledge such as genomics, proteomics and metallomics, are discussed herein.

Autopsy of invasive ductal pancreatic carcinoma that transformed into a tumor producing granulocyte colony-stimulating factor.

A 64-year-old woman was diagnosed with unresectable pancreatic cancer and underwent chemotherapy. However, the number of leukocytes significantly increased as the disease progressed. Serum G-CSF values also increased, and she eventually died on day 511 after diagnosis. Immediately after autopsy, immunohistochemical staining with an anti-G-CSF monoclonal antibody was positive in the poorly differentiated adenocarcinoma area of the primary pancreatic cancer and liver metastatic foci, but negative in the well-differentiated tubular adenocarcinoma part of the primary pancreatic cancer. During de-differentiation, invasive pancreatic ductal carcinoma appeared to have changed to a tumor that produced G-CSF.

Poly-2-methoxyethylacrylate-coated cardiopulmonary bypass circuit can reduce transfusion of platelet products compared to heparin-coated circuit during aortic arch surgery.

Several coating techniques for extracorporeal circulation have been developed to reduce the systemic inflammatory response during cardiopulmonary bypass (CPB). We compared the clinical effectiveness and biocompatibility of poly-2-methoxyethylacrylate (PMEA)- and heparin-coated CPB circuits in total aortic arch replacement (TAR) with the prolonged use of the bypass technique. Twenty patients who underwent elective TAR were divided randomly into two equal groups: group P (n = 10) to use PMEA-coated circuits and group H (n = 10) to use heparin-coated circuits. Clinical outcomes, hematological variables, and acute phase inflammatory response were analyzed perioperatively. Demographic, CPB, and clinical outcome data were similar for both groups. Hemoglobin and platelet count showed similar time-course curves. However, the amount of platelet products transfused intraoperatively was significantly larger in group H (group P 26.0 ± 7.0 units; group H 33.0 ± 6.7 units, p = 0.04). Total protein, and albumin levels were significantly higher in group P during and after the operation (total protein, p = 0.04; albumin, p = 0.02). The use of PMEA-coated circuit is associated with retainment of perioperative plasma proteins levels and may help to reduce transfusion of platelet products in TAR in comparison with the heparin-coated circuit.

[Evaluation of Portable Coagulation Analyzer in Comparison with Conventional Hospital Laboratory Instrument with Stratification of International Normalized Ratios by Therapeutic Upper Limit].

Point of care devices have been widely applied to outpatients receiving anticoagulation therapy with warfarin for monitoring prothrombin time-international normalized ratio (PT-INR) regularly. However, accuracy in measurement with the device remains undetermined when PT-INR exceeds therapeutic range. We evaluated the performance of a portable CoaguChek XS coagulation analyzer in comparison with a conventional laboratory method according to therapeutic and supra-therapeutic PT-INR values in cardiac outpatients on oral vitamin K antagonists. All participants were classified into 2 groups on the basis of PT-INR 3.0 by the laboratory method; therapeutic group less than or equal to 3.0 (n=48) and supra-therapeutic group above 3.0 (n=8). The correlation coefficients in therapeutic and in supra-therapeutic groups were r=0.82 and r=0.78, respectively (p<0.05). The difference in PT-INR between the laboratory method and the CoaguChek XS was significantly larger in supra-therapeutic group than therapeutic group (1.03±0.73 versus 0.34±0.26, p=0.042). Our study indicates that CoaguChek XS can be useful handheld coagulation analyzer to determine PT-INR rapidly; however, the device may underestimate PT-INR in supra-therapeutic range.

Non-islet cell tumor hypoglycemia caused by a big insulin-like growth factor II- producing hepatocellular carcinoma:an autopsy case report.

A 73-year-old man with a hepatocellular carcinoma was admitted to our hospital. He suffered from recurrent severe hypoglycemia. An autopsy was performed after his death. Anti-insulin-like growth factor II (IGF-II) monoclonal antibody immunostaining of the hepatocellular carcinoma was positive. Western immunoblot analysis of the serum revealed highly elevated IGF-II. Therefore, we diagnosed this case as a non-islet cell tumor hypoglycemia caused by a big IGF-II-producing hepatocellular carcinoma.

The effects of milk thistle (Silybum marianum) on human cytochrome P450 activity.

Milk thistle (Silybum marianum) extracts are widely used as a complementary and alternative treatment of various hepatic conditions and a host of other diseases/disorders. The active constituents of milk thistle supplements are believed to be the flavonolignans contained within the extracts. In vitro studies have suggested that some milk thistle components may significantly inhibit specific cytochrome P450 (P450) enzymes. However, determining the potential for clinically significant drug interactions with milk thistle products has been complicated by inconsistencies between in vitro and in vivo study results. The aim of the present study was to determine the effect of a standardized milk thistle supplement on major P450 drug-metabolizing enzymes after a 14-day exposure period. CYP1A2, CYP2C9, CYP2D6, and CYP3A4/5 activities were measured by simultaneously administering the four probe drugs, caffeine, tolbutamide, dextromethorphan, and midazolam, to nine healthy volunteers before and after exposure to a standardized milk thistle extract given thrice daily for 14 days. The three most abundant falvonolignans found in plasma, following exposure to milk thistle extracts, were silybin A, silybin B, and isosilybin B. The concentrations of these three major constituents were individually measured in study subjects as potential perpetrators. The peak concentrations and areas under the time-concentration curves of the four probe drugs were determined with the milk thistle administration. Exposure to milk thistle extract produced no significant influence on CYP1A2, CYP2C9, CYP2D6, or CYP3A4/5 activities.

Complete genome sequences of Lactococcus petauri strains 473AN and 473GN isolated from the blood culture of a Japanese patient with infective endocarditis.

Here, we report the complete genome sequences of Lactococcus petauri strains 473AN and 473GN, isolated from the blood culture of a Japanese patient with infective endocarditis. The complete genomes of 473AN and 473GN consist of single chromosomes of 2,065,772 and 2,094,461 bp, respectively.

Impact of a pharmacist-led collaborative approach to care for treatment of COVID-19 in the outpatient setting.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: The SARS-CoV-2 virus, causing COVID-19, remains a threat to patients and healthcare systems across the country. Oral antiviral therapy is available to reduce risk of patient hospitalization and death; however, limited access to medications, complex drug interactions, and the importance of timeliness in initiating therapy have proven to be challenging. This report aims to describe a pharmacist-driven telehealth service that provided safe and efficient access to antivirals for the treatment of COVID-19 and assess the population impacted. SUMMARY: This observational study was conducted from January 2022 to September 2023, during which time a COVID-19 pharmacist referral hub was utilized at Legacy Health. Patients documented to be positive for COVID-19 infection and who had a primary care provider within Legacy Health were included in the study. Demographics and descriptive data regarding antiviral prescribing for patients who were managed by an ambulatory care pharmacist were assessed. Patient demographics were statistically compared between groups to investigate antiviral access for marginalized populations. A total of 22,983 unique COVID-19 infections occurred during the study period, and ambulatory care pharmacists within Legacy Health managed 19.8% of all documented COVID-19 infections in our study population. The pharmacy team generated 3,820 antiviral prescriptions for treatment of COVID-19. The median time from symptom onset to antiviral prescription was 1 day. CONCLUSION: This pharmacist-led telehealth service had a significant impact in expanding access to COVID-19 antiviral treatment, which is pivotal in broadening access to timely COVID-19 antiviral treatment for all vulnerable patient groups when resources are limited.

Working environment for historically marginalized faculty, administrators, and librarians in pharmacy education.

INTRODUCTION: Promoting diversity among faculty, administrators, and librarians in schools and colleges of pharmacy (SCOP) would be beneficial for the recruitment and retention of students from diverse backgrounds. Graduating such diverse pharmacists could assist in reducing healthcare disparities. Promoting diversity requires a climate that is inclusive of people from all backgrounds. The goal of this study was to examine the working environment of historically marginalized faculty, administrators, and librarians within pharmacy education. METHODS: An electronic survey was administered to all faculty, administrators, and librarians listed in the American Association of Colleges of Pharmacy roster. RESULTS: Responses from 339 participants were analyzed. Twenty-seven percent of these participants either observed or personally experienced misconduct during the previous five years. When action was taken, it resulted in the cessation of the misconduct only 38% of the time. Respondents most frequently identified the following as ways to make it easier to address misconduct: support from supervisors, support from peers, and education on how to address misconduct. CONCLUSIONS: Exclusionary, intimidating, offensive, and/or hostile communication/behaviors towards historically marginalized faculty, administrators, and librarians do exist in SCOP. The academy should work towards promoting diversity, equity, and inclusion in SCOP through education and provide administrative and peer support for reporting and managing professional misconduct.

Baseline Assessment of Systemic Racism Education in Pharmacy Curricula.

Objective. To determine, by survey, the inclusion of systemic racism education in US Doctor of Pharmacy (PharmD) curricula and identify barriers and facilitators to addressing this content.Methods. A survey was developed and distributed to curricular representatives at US colleges and schools of pharmacy. The survey assessed inclusion of systemic racism education in curricula, faculty involvement in teaching systemic racism content, barriers to adding systemic racism content in curricula, and future curricular plans. Data were analyzed using descriptive statistics for institutional background information, curricular content, and barriers to inclusion. Relationships between the inclusion of systemic racism content at public versus private programs were examined, and associations between traditional and accelerated programs were assessed.Results. Fifty-eight colleges and schools of pharmacy provided usable responses. Of the respondents, 84% indicated that teaching systemic racism content and its impact on health and health care was a low priority. For 24% of respondents, systemic racism content was not currently included in their curriculum, while 34% indicated that systemic racism content was included in one or more courses or modules but was not a focus. Despite systemic racism content being offered in any didactic year, it was rarely included in experiential curricula. Top barriers to inclusion were lack of faculty knowledge and comfort with content and limited curricular space. No significant differences were found between program types.Conclusion. Based on the current level of systemic racism education and barriers to inclusion, faculty need training and resources to teach systemic racism concepts within pharmacy curricula. The inclusion of systemic racism concepts and guidance in the Accreditation Council for Pharmacy Education's Accreditation Standards could help to drive meaningful change and promote health equity.

Impact of an educational flyer and sensitization on performance-enhancement attitudes of bodybuilders in United Arab Emirates.

Background: A high proportion of bodybuilders use supplements to improve performance, with some turning to prohibited substances and methods. The attitudes of bodybuilders towards performance enhancement may be gauged through surveys such as the Performance Enhancement Attitude Scales (PEAS). Educational interventions are recommended as part of anti-doping measures. The objective of this project was to assess the impact of a pharmacy-led intervention using an antidoping educational flyer and the performance enhancement attitude scale to measure the attitude of bodybuilders in the United Arab Emirates (UAE). Methods: The PEAS eight-item short form questionnaire was administered to male bodybuilders in the UAE. The PEAS was conducted before and after administration of an educational flyer concerning the problems associated with supplement use among bodybuilders. The Wilcoxon Signed-Rank and Kruskal Wallis tests were used for data analysis. Results: A total of 218 bodybuilders, who reported taking dietary supplements, filled out the survey both pre and post viewing the antidoping educational flyer. A difference was observed between the full-time professional bodybuilders, students, and part-time bodybuilders with other primary occupations (p-value <0.05). In addition, PEAS score decreased among the study population for all eight PEAS items (p-value <0.05). Conclusions: The pharmacy-led intervention using an antidoping educational flyer and sensitization by PEAS achieved more favorable scores, suggesting a significant shift of opinion toward avoiding use of performance enhancing substances among the bodybuilder study population. More research is required on sustaining the attitude and demonstrating the impact on doping behavior.

Characteristics of Successful International Pharmacy Partnerships.

Recommendations for global pharmacy collaborations are predominately derived from US institutions. This study utilized semi-structured interviews of global collaborators to assess important partnership components. Interviewees stated personal connections and understanding of each other's programs/systems were key components. Additionally, collaborators indicate that mutual benefits between partners can exist without the requirement for bidirectional exchange of learning experiences, and request and value partners and learners who are culturally aware, global citizens. This structured interview approach provided key insight into how to develop mutually beneficial, sustainable partnerships and provides additional confirmation that the five pillars of global engagement align with an international audience.

Guidance for Qualitative Research Manuscripts in Pharmacy Education.

The goal of this Best Practice Review is to support researchers in successfully preparing and publishing qualitative research in pharmacy education. Standard practice from the literature and journals' guidance from related fields were reviewed, and recommendations and resources applicable to qualitative research in pharmacy education were compiled for researchers planning to conduct and publish qualitative research. This review provides recommendations, not requirements, for publication in the Journal and is intended to be a guide, especially for authors and reviewers relatively new to the field of qualitative research. Additionally, researchers planning to publish their qualitative research are advised to review available best practices and standards, such as the Consolidated Criteria for Reporting Qualitative Research checklist and the Standards for Reporting Qualitative Research. Given the diverse methodology of qualitative research, it is important for authors to provide sufficient details and justifications of selected methods for transparency and to report collected results in a manner that allows reviewers and readers to adequately assess the validity of their study and the applicability of the findings.

Experience-dependent plasticity of the optomotor response in Drosophila melanogaster.

Experience in early life can affect the development of the nervous system. There is now evidence that experience-dependent plasticity exists in adult insects. To uncover the molecular basis of plasticity, an invertebrate model, such as Drosophila melanogaster, is a powerful tool, as many established genetic and molecular methods can be applied. To establish a model system in which behavioral plasticity can be examined, we investigated the optomotor response, a behavior common to most sight-reliant animals, in Drosophila and found that the response could be modified by the level of light during rearing. The angle turned by the head in response to a moving stimulus was used to quantify the response. Deprivation of light increased the response to low-contrast stimuli in wild-type Drosophila at 4 days after eclosion and this plastic change did not appear in rutabaga, a known mutant defective in short-term memory. In addition, the change was transient and was markedly decreased at 6 days after eclosion. Further, we found that Dark-flies, which have been kept in constant darkness for more than 50 years, showed a higher response to low-contrast stimuli even at 6 days after eclosion compared to wild type and this characteristic was not lost in Dark-flies placed in a normal light environment for 2 generations, suggesting that this high response has a hereditary nature. Thus, our model system can be used to examine how the environment affects behaviors.

The contribution of serotonin 5-HT2C and melanocortin-4 receptors to the satiety signaling of glucagon-like peptide 1 and liraglutide, a glucagon-like peptide 1 receptor agonist, in mice.

Glucagon-like peptide 1 (GLP-1), an insulinotropic gastrointestinal peptide produced mainly from intestinal endocrine L-cells, and liraglutide, a GLP-1 receptor (GLP-1R) agonist, induce satiety. The serotonin 5-HT2C receptor (5-HT2CR) and melanoroctin-4 receptor (MC4R) are involved in the regulation of food intake. Here we show that systemic administration of GLP-1 (50 and 200µg/kg)-induced anorexia was blunted in mice with a 5HT2CR null mutation, and was attenuated in mice with a heterozygous MC4R mutation. On the other hand, systemic administration of liraglutide (50 and 100µg/kg) suppressed food intake in mice lacking 5-HT2CR, mice with a heterozygous mutation of MC4R and wild-type mice matched for age. Moreover, once-daily consecutive intraperitoneal administration of liraglutide (100µg/kg) over 3days significantly suppressed daily food intake and body weight in mice with a heterozygous mutation of MC4R as well as wild-type mice. These findings suggest that GLP-1 and liraglutide induce anorexia via different central pathways.

Characterization of zebrafish GABAA receptor subunits.

γ-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system, exerts its effect through the activation of GABA receptors. GABAA receptors are ligand-gated chloride channels composed of five subunit proteins. Mammals have 19 different GABAA receptor subunits (α1-6, ß1-3, γ1-3, δ, ε, π, θ, and ρ1-3), the physiological properties of which have been assayed by electrophysiology. However, the evolutionary conservation of the physiological characteristics of diverged GABAA receptor subunits remains unclear. Zebrafish have 23 subunits (α1, α2a, α2b, α3-5, α6a, α6b, ß1-4, γ1-3, δ, π, ζ, ρ1, ρ2a, ρ2b, ρ3a, and ρ3b), but the electrophysiological properties of these subunits have not been explored. In this study, we cloned the coding sequences for zebrafish GABAA receptor subunits and investigated their expression patterns in larval zebrafish by whole-mount in situ hybridization. We also performed electrophysiological recordings of GABA-evoked currents from Xenopus oocytes injected with one or multiple zebrafish GABAA receptor subunit cRNAs and calculated the half-maximal effective concentrations (EC50s) for each. Our results revealed the spatial expressions and electrophysiological GABA sensitivities of zebrafish GABAA receptors, suggesting that the properties of GABAA receptor subunits are conserved among vertebrates.

Reconsidering Sports Pharmacists and Anti-Doping Education as the World Celebrates the Olympic and Paralympic Games.

The Tokyo Olympic and Paralympic Games in 2021 presented an opportunity for pharmacists to recognize the uniqueness of sports pharmacy as a developing field and to understand the importance of anti-doping education among patient-athletes. Patient-athletes make up a distinct patient population, and pharmacists are well positioned to support athletes' therapeutic decisions. Pharmacists need to be able to search for and interpret drug information to take care of this special population appropriately. The purpose of this commentary is to facilitate a discussion on what changes or reinforcement might help train pharmacists to become equipped with adequate knowledge and skills to support safe use of drugs among patient-athletes. While effective resources and tools have become more widely available, pharmacists' awareness of and training in the field of sports pharmacy continue to be needed. No matter where they practice, pharmacists should be ready to promote "the spirit of sport" and defend the importance of "clean" sport for their patient-athletes.