Clinical Impact of the CYP2C19 Gene on Diazepam for the Management of Alcohol Withdrawal Syndrome.

Diazepam is a benzodiazepine widely prescribed for the management of patients with severe alcohol withdrawal syndrome to prevent agitation, withdrawal seizures, and delirium tremens. Despite standard dosing of diazepam, a subset of patients experience refractory withdrawal syndromes or adverse drug reactions, such as impaired motor coordination, dizziness, and slurred speech. The CYP2C19 and CYP3A4 enzymes play a key role in the biotransformation of diazepam. Given the highly polymorphic nature of the CYP2C19 gene, we reviewed the clinical impact of variants in the CYP2C19 gene on both the pharmacokinetics of diazepam and treatment outcomes related to the management of alcohol withdrawal syndrome.

Vericiguat: The First Soluble Guanylate Cyclase Stimulator for Reduction of Cardiovascular Death and Heart Failure Hospitalization in Patients With Heart Failure Reduced Ejection Fraction.

Objective: This study aims to review the pharmacology, efficacy, and safety of the soluble guanylate cyclase stimulator, vericiguat, in patients with symptomatic congestive heart failure with ejection fraction less than 45% for the reduction of cardiovascular deaths. Also, to evaluate heart failure-related hospitalization in patients following a hospital discharge secondary to heart failure or those that require outpatient intravenous diuretics. Data source: MEDLINE/Pubmed and National Institutes of Health Clinical Trial Registry were searched between January 1989 to February 2021 using the following terms: vericiguat, soluble guanylate cyclase stimulator, heart failure, (was also known as) BAY 1021189. Study Selection and Data Extraction: The following study designs were included in the analysis: phase I, II, and III clinical trials; systematic reviews; and meta-analyses. Articles were included if they were published in English and evaluated vericiguat pharmacology, pharmacokinetics, efficacy, and safety. Data Synthesis: The Food and Drug Administration approved vericiguat for the reduction of cardiovascular death and hospitalization after having a related hospitalization or the need for outpatient intravenous diuretics, in those with symptomatic chronic heart failure and ejection fraction less than 45%. In the VICTORIA trial, vericiguat demonstrated a 10% reduction in risk of death from cardiovascular causes or first hospitalization for heart failure compared with placebo. Vericiguat was well tolerated overall with hypotension, syncope, and anemia noted as the most common side effects, similar to the other agent in its class. Conclusion: Vericiguat may be appropriate as add-on therapy for patients already on guideline-directed medical therapy with recent decompensated HFrEF to reduce hospitalization.

Evaluation of SOAP note performance in a pharmacotherapeutics course after implementation of a peer-review process.

INTRODUCTION: Subjective, objective, assessment, and plan (SOAP) notes are widely utilized within pharmacy curricula. Implementation of a peer-review process for these assignments may improve student competence. Evidence is lacking regarding correlation between student-to-student peer-review and faculty grades for SOAP notes and correlation of SOAP note peer-evaluation to individual performance. METHODS: Third year pharmacy students completed two SOAP notes in Pharmacotherapeutics IV. A peer-review process was implemented in spring 2020. After each SOAP note, students were assigned a peer's assignment to evaluate utilizing the same 50-point rubric as the faculty. SOAP note grades were compared between the 2019 and 2020 cohorts. RESULTS: Analysis included 98 students in spring 2019 and 92 students in 2020. SOAP note faculty grades were different between 2019 and 2020 for the first SOAP note (37.6 vs. 41.1, P < .001) but not for the second (42.3 vs. 42.7, P = .49). Peer-review grades were higher for both SOAP notes compared to faculty grades. Peer-review grades did not differ between the first and second SOAP notes (45.5 vs. 45.6) while faculty grades did (41.2 vs. 42.7). The difference in scores from peer-review compared to faculty grades was -4.4 points for the first SOAP note and - 2.9 points for the second SOAP note (P = .08). CONCLUSIONS: The peer-review process did not appear to improve SOAP note performance. Students tended to score better on the second note and appeared to gain proficiency in the peer evaluation process, suggesting a possible benefit of including additional SOAP notes.

Sodium-Glucose Cotransporter 2 Inhibitor Use Associated With Fournier's Gangrene: A Review of Case Reports and Spontaneous Post-Marketing Cases.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are effective for glycemic control and have demonstrated cardiorenal benefits. The U.S. Food and Drug Administration (FDA) released a boxed warning in 2018 regarding the potential development of Fournier's gangrene (FG) with the use of SGLT2 inhibitors. FG is a serious perineal infection with a mortality rate of up to 88% in some cases. OBJECTIVES: To report spontaneous post-marketing cases from the FDA Adverse Event Reporting System (FAERS) database and case reports from the literature of FG associated with the use of SGLT2 inhibitors and to determine whether correlations exist with specific agents. METHODS: A search of the FAERS database was conducted to identify reported cases of FG associated with the use of any FDA-approved SGLT2 inhibitor between 1 March 2013 and 30 June 2020. Additionally, a literature search was conducted of PubMed, Embase, and the Cochrane library using PRISMA guidelines to identify case reports of FG with the use of SGLT2 inhibitors up to 9 October 2020. RESULTS: A total of 491 cases from the FAERS database were included for review. Descriptive analysis depicted more cases in the empagliflozin, canagliflozin, and dapagliflozin groups than in the ertugliflozin group. Nine case reports were included from the literature review; four attributed to dapagliflozin, three to empagliflozin, and two to canagliflozin. The median ages from cases reported in the FAERS database and from the literature review were 54 and 52 years, respectively. In both datasets, males had a higher incidence of FG than females. Additional data reported include clinical outcomes and concomitant antihyperglycemic medications. CONCLUSION: Consistent findings are noted in this systematic review and warrant further investigation to elucidate the association between SGLT2 inhibitor use and the development of FG. These results may drive enhanced prescribing patterns to consider patient-specific risk factors and timely monitoring, especially as more indications are approved related to these medications' cardiorenal protective properties.

Trichodysplasia spinulosa in a child: Identification of trichodysplasia spinulosa-associated polyomavirus in skin, serum, and urine.

A 6-year-old girl with a history of chronic immunosuppression following small bowel and colon transplantation for tufting enteropathy presented with a diffuse, facial-predominant eruption composed of pink-to-skin-colored papules with central white dystrophic spicules. Histology from a punch biopsy and polymerase chain reaction (PCR) from plucked spicules confirmed a diagnosis of trichodysplasia spinulosa (TS). Additional molecular studies identified several strains of the trichodysplasia spinulosa-associated polyomavirus infecting multiple tissues of the patient, confirming the systemic nature of trichodysplasia spinulosa infections.

Complications in body contouring stratified according to weight loss method.

BACKGROUND: Body contouring procedures following massive weight loss have become increasingly common and, unfortunately, continue to be associated with a high complication rate. OBJECTIVE: To evaluate how weight loss method affects complications following abdominally based body contouring procedures. METHODS: Patients undergoing abdominally based contouring procedures were retrospectively evaluated over an 11-year period and stratified into two groups based on method of weight loss: diet and exercise; or bariatric surgery. Complications, including seroma, wound dehiscence, skin necrosis, infection, hematoma and venous thromboembolism, were included if they required intervention. An adjusted logistic model was used to examine the effect of weight loss method on aggregate complication rates. RESULTS: A total of 307 patients were included: 77 (25%) lost weight through diet and exercise; and 230 (75%) through bariatric surgery. Results from the logistic model showed no difference in complication rates between weight loss methods (OR 1.01 [95% CI 0.51 to 2.02]). However, there was a strong correlation between body mass index at the time of surgery and complication rates (OR 1.05 [95% CI 1.02 to 1.08]; P<0.01). CONCLUSIONS: The findings reveal no difference in complication rates following abdominal body contouring procedures attributable to method of weight loss. Rather, there was a proportional rise in complication rates in patients with a higher body mass index at the time of surgery. Surgeons and patients should be aware of this trend, and it should be part of any discussion of abdominal body contouring procedures and informing patients of their risk profile.

HISTORIQUE: Les interventions de remodelage du corps après une perte de poids massive sont de plus en plus courantes. Malheureusement, elles continuent d'être associées à un taux de complication élevé. OBJECTIF: Évaluer l'influence de la méthode de perte de poids sur les complications après des interventions de remodelage de l'abdomen. MÉTHODOLOGIE: Les chercheurs ont fait l'évaluation rétrospective de patients qui avaient subi des interventions de remodelage sur une période de 11 ans et les ont stratifiés en deux groupes, selon la méthode de perte de poids: régime et exercice ou chirurgie bariatrique. Ils ont inclus les complications qui avaient nécessité une intervention, y compris le sérome, la déhiscence de la plaie, la nécrose cutanée, l'infection, l'hématome et la thromboembolie veineuse. Ils ont utilisé un modèle logistique rajusté pour examiner l'effet de la méthode de perte de poids sur les taux de complication globaux. RÉSULTATS: Au total, 307 patients ont été inclus dans l'étude, dont 77 (25 %) ont perdu du poids par suite d'un régime et d'exercice et 230 (75 %) après une chirurgie bariatrique. Les résultats du modèle logistique n'ont révélé aucune différence dans les taux de complications selon la méthode de perte de poids (RC 1,01 [95 % IC 0,51 à 2,02]). Cependant, ils ont constaté une forte corrélation entre l'indice de masse corporelle au moment de l'opération et les taux de complications (RC 1,05 [95 % IC 1,02 à 1,08]; P<0,01). CONCLUSIONS: Les résultats n'ont révélé aucune différence dans les taux de complication attribuables à la méthode de perte de poids après des interventions de remodelage abdominal. Ils ont plutôt démontré une augmentation proportionnelle des taux de complication chez les patients dont l'indice de masse corporelle était plus élevé lors de l'opération. Les chirurgiens et les patients devraient connaître cette tendance, qu'il faudrait intégrer aux discussions sur les interventions de remodelage abdominal et à l'information aux patients sur leur profil de risque.

Dermal damage promoted by repeated low-level UV-A1 exposure despite tanning response in human skin.

IMPORTANCE: Solar UV irradiation causes photoaging, characterized by fragmentation and reduced production of type I collagen fibrils that provide strength to skin. Exposure to UV-B irradiation (280-320 nm) causes these changes by inducing matrix metalloproteinase 1 and suppressing type I collagen synthesis. The role of UV-A irradiation (320-400 nm) in promoting similar molecular alterations is less clear yet important to consider because it is 10 to 100 times more abundant in natural sunlight than UV-B irradiation and penetrates deeper into the dermis than UV-B irradiation. Most (approximately 75%) of solar UV-A irradiation is composed of UV-A1 irradiation (340-400 nm), which is also the primary component of tanning beds. OBJECTIVE: To evaluate the effects of low levels of UV-A1 irradiation, as might be encountered in daily life, on expression of matrix metalloproteinase 1 and type I procollagen (the precursor of type I collagen). DESIGN, SETTING, AND PARTICIPANTS: In vivo biochemical analyses were conducted after UV-A1 irradiation of normal human skin at an academic referral center. Participants included 22 healthy individuals without skin disease. MAIN OUTCOMES AND MEASURES: Skin pigmentation was measured by a color meter (chromometer) under the L* variable (luminescence), which ranges from 0 (black) to 100 (white). Gene expression in skin samples was assessed by real-time polymerase chain reaction. RESULTS: Lightly pigmented human skin (L* >65) was exposed up to 4 times (1 exposure/d) to UV-A1 irradiation at a low dose (20 J/cm2), mimicking UV-A levels from strong sun exposure lasting approximately 2 hours. A single exposure to low-dose UV-A1 irradiation darkened skin slightly and did not alter matrix metalloproteinase 1 or type I procollagen gene expression. With repeated low-dose UV-A1 irradiation, skin darkened incrementally with each exposure. Despite this darkening, 2 or more exposures to low-dose UV-A1 irradiation significantly induced matrix metalloproteinase 1 gene expression, which increased progressively with successive exposures. Repeated UV-A1 exposures did not suppress type I procollagen expression. CONCLUSIONS AND RELEVANCE: A limited number of low-dose UV-A1 exposures, as commonly experienced in daily life, potentially promotes photoaging by affecting breakdown, rather than synthesis, of collagen. Progressive skin darkening in response to repeated low-dose UV-A1 exposures in lightly pigmented individuals does not prevent UV-A1-induced collagenolytic changes. Therefore, for optimal protection against skin damage, sunscreen formulations should filter all UV wavelengths, including UV-A1 irradiation.