Trends in Light and Temperature Sensitivity Recommendations among Licensed Biotechnology Drug Products.

PURPOSE: Inherent structural and functional properties of biotechnology-derived therapeutic biologics make them susceptible to light- and temperature-induced degradation and consequently can influence their quality. Photosensitivity of therapeutic proteins continues to be examined, but the commonalities and trends of storage conditions and information about light and temperature sensitivity among currently licensed therapeutic proteins has not been previously surveyed. METHODS: Using a comprehensive and relational database approach, we conducted a scientific survey of all licensed biotechnology-derived drug products with the goal of providing evidence-based information about recommended storage conditions of formulations sorted by light- and temperature-related attributes as described for each product at licensure. RESULTS: We report the prevalence of indications for light and temperature sensitivity in formulations categorized by their presentation type, number of doses, container type, dosage form and active molecule type. We also report the storage temperature range across formulations and diluents for reconstitution and dilution. Formulations with excipients that potentially facilitate light-induced and thermal degradation were also noted. CONCLUSIONS: The result of our analysis indicates that light and temperature sensitivity are prevalent across therapeutic protein formulations. However, when a formulation is reconstituted or diluted, both light and temperature sensitivity are less clear. In addition, light and temperature sensitivity are more well defined in liquid formulations than lyophilized powder formulations, and more well defined in products manufactured in autoinjectors, prefilled-syringes, and pens than products in vials. Overall, our report provides a data-driven summary of storage conditions among therapeutic protein formulations to support the development of future biologic drug products.

Severe late-onset ovarian hyperstimulation syndrome presenting with liver dysfunction after in vitro fertilization: A case report.

Ovarian hyperstimulation syndrome (OHSS) is a feared complication of controlled ovarian stimulation (COS) and can be associated with significant morbidity and mortality. Risk factors for OHSS include a history of OHSS, young age, low body mass index (BMI), polycystic ovary syndrome, elevated serum levels of anti-Müllerian hormone (AMH), large number of recruited follicles, elevated serum levels of estradiol, and higher gonadotropin doses during COS. However, OHSS may develop in patients with minimal risk factors. We present the case of a patient with minimal risk factors who developed severe late-onset OHSS in early pregnancy with liver dysfunction requiring hospitalization. After hospital discharge, her pregnancy resulted in a term live birth. We recommend that clinicians include OHSS in the differential diagnosis of elevated levels of liver enzymes in early pregnancy.

Intervention documentation of second- to fourth-year pharmacy students during clinical experiential rotations.

INTRODUCTION: The objective of this study was to evaluate pharmacy student intervention documentation during their clinical experiential rotations and to gain insight on their perceptions of this experience. METHODS: This was an institutional review board approved descriptive study of pharmacy student interventions documented during one academic year. Students documented interventions using a pharmacy-specific system in the electronic medical record. Pharmacy student feedback regarding the process and utility of intervention documentation was assessed using a brief anonymous, voluntary, three-min online survey tool. RESULTS: In total, 894 clinical interventions were documented by 32 students (585 by 11 fourth-year students, 309 by 21  second- and third-year students). Most interventions were categorized as other (28%), followed by change in dose, frequency or, route (26.5%). The acceptance rate was 89.5% and associated cost savings were $166,551 ($186.30 per intervention). Student survey responses were generally positive and recommended continuing the documentation process in the future. CONCLUSIONS: This study provides insight into the concept of second- and third-year pharmacy student clinical intervention documentation, with comparison to fourth-year documentation. Future studies exploring pharmacy student intervention documentation may be valuable (e.g., expanding pharmacy services, demonstrating student impact on patient care, strategies to best facilitate learning).

A Comprehensive Scientific Survey of Excipients Used in Currently Marketed, Therapeutic Biological Drug Products.

PURPOSE: The steady development of biotechnology-derived therapeutic biologics over the last few decades has generated drugs that are now standard medical treatments for a range of indications. While the development of protein products has surged in recent years, the formulation and delivery of these complex molecules have relied on drug-specific studies and, in some instances, data from non-proteinaceous drug products. The commonalities, trends, and gaps in excipient technologies used to support the development of therapeutic proteins largely remain unexplored due to the drug-specific nature of many formulations. METHODS: Using a comprehensive and relational database approach, we aimed to provide a scientific survey of all approved or licensed biotechnology-derived drug products with the goal of providing evidence-based information on common attributes and trending features in protein product excipients. We examined 665 formulations, and 395 unique formulations based on having unique excipients within them, that supported 211 therapeutic proteins as of June 2020. RESULTS: We report the prevalence of each excipient class and excipient chemical used in eight different drug types including monoclonal antibodies, antibody conjugates, cytokines and growth factors, enzymes, polypeptide hormones, pulmonary surfactants, recombinant fusion proteins, and toxins. We also report the prevalence by excipient type among all therapeutic proteins, in the context of each drug's recommended pH range, concentration ranges for excipients, and route of administration. CONCLUSIONS: The results of our analyses indicate certain excipients common to monoclonal antibodies, cytokines, and polypeptide hormones. We also report on excipients unique to protein drug products, such as amino acids, solubilizers, and lyoprotectants. Overall, our report summarizes the current landscape of excipients used in marketed biotechnology-derived therapeutic biologic products.

Pharmacist Perception of a Mobile Application Audience Response System for Remote Pharmacy Continuing Education Participants.

INTRODUCTION: Interactive audience response during continuing education (CE) in pharmacy practice increases audience involvement. However, remote-site participants may not have access to interactive technology. This study explores the perceptions of a mobile application audience response system (ARS) by remote pharmacy CE participants. Secondarily, we evaluatedinterest in continued use of ARS, as well as willingness to use as an assessment tool for CE effectiveness. METHODS: Pharmacists participating in CE sessions remotely within a health system were provided a unique ARS session code to enter into a free mobile application. Participants then responded to ARS presentation questions. An online survey link was e-mailed to all potential remote participants inquiring about perceptions of ARS use. RESULTS: Of the 52 potential remote users, 28 (53.8%) responded to the survey. The top 3 positive responses included the availability of free software (71.4%), anonymity (57.1%), and ease of use (53.6%). Top 2 barriers included slowing the process down (14.3%) and requiring the use of application software (14.3%). DISCUSSION: Interactive software during pharmacy CE lectures for participants at remote locations within a health system was well accepted. ARS should be considered and further studied for CE lectures at institutions with remote participants.

Effects of the harmful algae, Alexandrium catenella and Dinophysis acuminata, on the survival, growth, and swimming activity of early life stages of forage fish.

The effects of co-occurring harmful algal blooms (HABs) on marine organisms is largely unknown. We assessed the individual and combined impacts of the toxin producing HABs, Alexandrium catenella and Dinophysis acuminata, and a non-toxin-producing HAB (Gymnodinium instriatum) on early life stages of two estuarine fish species (Menidia beryllina and Cyprinodon variegatus). Lethal (i.e. time to death) and sublethal (i.e. growth, grazing rate, and swimming activity) effects of cultured HABs were investigated for eleutheroembryo and larval life stages. Mixed algal treatments (i.e. A. catenella and D. acuminata mixtures) were often equally toxic as A. catenella monoculture treatments alone, although responses depended on the fish species and life stage. Fish exposed to toxin producing HABs died significantly sooner (i.e. <1-3 days) than controls. Significant differences in sublethal effects were also found between fed controls and toxic HAB treatments, although responses were often similar to G. instriatum or starved controls. Collectively, the results demonstrate that HABs may reduce fish productivity and fitness.

Pharmacy Student Monitoring of Direct Oral Anticoagulants.

BACKGROUND: Best practice recommendations are lacking. Thus far, literature has described pharmacist-led DOAC monitoring. OBJECTIVE: The purpose of this study is to describe a DOAC monitoring program involving pharmacy students. METHODS: This was an observational analysis of a quality improvement initiative. A clinical pharmacist preceptor identified clinic patients taking DOACs by running a report using the electronic medical record. Pharmacy students conducted chart reviews, called pharmacies for 6-month refill histories, and interviewed and educated patients. Findings were communicated to the care team and interventions were performed as applicable with the preceptor. RESULTS: Of 90 patients included, the mean age was 63 years, 54% were female, and 65.6% were black or African American. Rivaroxaban and apixaban were used most commonly. Sixty-two percent of DOACs were prescribed for atrial fibrillation/flutter, while 32.2% for venous thromboembolism. The mean MPR was 77.1%, with 27.7% of patients having an MPR ≤60%. Of the 136 student-led interventions, 25.2% involved medication access, 24.4% adherence education, 20.7% processing refills, 14.8% laboratory monitoring recommendations, 8.9% switching or recommending switching to another anticoagulant, and 4.4% stopping a nonsteroidal anti-inflammatory drug or aspirin. CONCLUSION: Pharmacy students can help to ensure medication safety and effective use of DOACs.

Premature Ovarian Insufficiency: Procreative Management and Preventive Strategies.

Premature ovarian insufficiency (POI) is the loss of normal hormonal and reproductive function of ovaries in women before age 40 as the result of premature depletion of oocytes. The incidence of POI increases with age in reproductive-aged women, and it is highest in women by the age of 40 years. Reproductive function and the ability to have children is a defining factor in quality of life for many women. There are several methods of fertility preservation available to women with POI. Procreative management and preventive strategies for women with or at risk for POI are reviewed.

Clinical response to unintentionally rapid infusion of drotrecogin alfa (activated).

PURPOSE: The case of a patient with severe sepsis who received a bolus dose of 184 microg/kg of drotrecogin alfa (activated) over one hour is reported. SUMMARY: An 84-year-old woman who had undergone right total knee replacement was admitted to the hospital from a rehabilitation facility with an initial diagnosis of mental status changes and a suspected urinary tract infection. Examination of the patient's incision from her recent knee surgery revealed a discharge, and a culture was obtained. The patient was diagnosed with sepsis, intubated, and transferred to the intensive care unit. Multiple antibiotics were administered, but the patient's condition continued to deteriorate. In addition, the patient developed acute renal failure, required a ventilator, had cyanotic limbs, and had partially compensated metabolic acidosis. On hospital day 7, drotrecogin alfa (activated) was initiated. She inadvertently received an infusion of 184 microg/kg of drotrecogin alfa over 1 hour. Nine hours later, she received drotrecogin alfa 24 microg/kg/hr for 95 hours. The patient's clinical status was improved after the initial infusion. Peripheral limb cyanosis was markedly decreased, with pink, warm extremities. In addition, the patient's clinical laboratory test values improved after administration of drotrecogin alfa. However, the patient was unable to recover fully from the acute kidney failure and was discharged to hospice care. CONCLUSION: A drotrecogin alfa dose of 184 microg/kg i.v. was erroneously administered over 1 hour to a patient with sepsis. Nine hours later, a drotrecogin alfa infusion of 24 microg/kg/hr was started and continued for 95 hours. The patient improved clinically and had no apparent adverse events.

Fondaparinux therapy in a hemodialysis patient with heparin-induced thrombocytopenia type II.

PURPOSE: The successful use of fondaparinux in a hemodialysis patient with heparin-induced thrombocytopenia type II (HIT II) is reported. SUMMARY: An 85-year-old, 68-kg Caucasian woman came to the emergency department with shortness of breath and exertional chest pain radiating to the neck. Testing revealed non-ST-segment elevation myocardial infarction, severe coronary artery disease, mitral regurgitation, left ventricular dysfunction, an ejection fraction of 25-30%, and pulmonary arterial hypertension. I.V. unfractionated heparin was given for therapeutic anticoagulation per hospital protocol and discontinued on hospital day 3 before mitral valve repair and coronary bypass procedure. Postoperatively unfractionated heparin and low-molecular-weight heparin were avoided because of a reduction in the platelet count and suspicion of HIT. Instead, the patient was placed on sequential compression devices in addition to aspirin for prophylaxis of deep venous thrombosis. By postoperative day 6, the patient's platelet count dropped 76% from baseline, and the patient was found to have heparin-dependent platelet factor 4 antibodies. Argatroban infusion was initiated but discontinued after 2 days due to bleeding. Fondaparinux was ordered for anticoagulation therapy. By hospital day 8, the patient developed renal insufficiency requiring hemodialysis and adjustment of the fondaparinux regimen. During the 30-day course of fondaparinux, the patient did not experience thromboembolic events or bleeding and did not require transfusions. There was no clotting within hemodialysis membranes, and her hepatic function improved by the time of her discharge. CONCLUSION: Fondaparinux was used in a hemodialysis patient with HIT II without the development of thromboembolic, hemodialysis-clotting, thrombocytopenic, or hemorrhagic complications. The patient's platelet count remained in the normal range during the 30-day course of fondaparinux.

Effects of commercial energy drink consumption on athletic performance and body composition.

Energy drinks are frequently marketed to individuals interested in athletics and an active lifestyle. From 2001 to 2008, estimates of energy drink use in adolescent to middle-aged populations ranged from 24% to 56%. Most energy drinks feature caffeine and a combination of other components, including taurine, sucrose, guarana, ginseng, niacin, pyridoxine, and cyanocobalamin. This article examines the evidence for 2 commonly purported uses of energy drinks: athletic performance enhancement and weight loss. Observed ergogenic benefits of energy drinks are likely attributable to caffeine and glucose content. There is conflicting evidence regarding the impact of energy drinks on weight loss, although some data suggest that combining energy drink use with exercise may enhance body fat reduction. As with any pharmacologically active substance, energy drinks are associated with adverse effects. Combining energy drinks with alcohol exacerbates safety concerns and is an increasingly common practice contributing to toxic jock identity among college-aged male athletes. Practitioners should monitor identified populations likely to consume these loosely regulated beverages.

Universal perinatal depression screening in an Academic Medical Center.

OBJECTIVE: To develop a department-based program to identify and treat women at risk for perinatal depression. METHODS: Private and employed physician groups were engaged to conduct antepartum maternal depression screening using the Edinburgh Postnatal Depression Scale. A comprehensive program was established to ensure that patients identified as being at risk would receive appropriate care. The program 1) developed a network of existing community mental health providers to accommodate screen-positive referrals, 2) created a 24/7 hotline staffed by mental health workers to respond to urgent/emergent patient needs, 3) provided nursing and physician education via a comprehensive curriculum on perinatal depression, and 4) facilitated outpatient depression screening that included a centralized scoring and referral system. RESULTS: A total of 4,322 women completed 4,558 screens during the initial 24 months (June 2003-May 2005). Although initial uptake of the screening program was gradual, all 20 departmental obstetric practices were screening their patients at the end of the first year. Depression screening was accomplished between 28-32 weeks of gestation, and postpartum screening (during the 6-week postpartum visit) was subsequently added. Overall, 11.1% of women screened positive in the antenatal period, and 7.3% screened positive in the postnatal period. Three hundred three women were referred for evaluation and care. CONCLUSION: Department-based, perinatal depression screening was feasible when individual physician practices were not required to develop the infrastructure necessary to respond to at-risk patients. We believe that the provision of clinical safety nets (mental health provider network and the hotline) were essential to the universal acceptance of this program by practitioners. LEVEL OF EVIDENCE: III.