Characterization of a Musculoskeletal Syndrome of Enthesitis and Arthritis in Patients With Atopic Dermatitis Treated With Dupilumab, an Interleukin-4/13 Inhibitor.

OBJECTIVE: To characterize the presentation and outcomes of patients with atopic dermatitis (AD) who developed musculoskeletal symptoms after treatment with dupilumab, a human IgG4 monoclonal antibody that blocks the functions of interleukin-4 (IL-4) and IL-13, key pathologic pathways in AD. METHODS: This article reports an observational cohort of patients receiving dupilumab who developed new-onset musculoskeletal symptoms after dupilumab therapy at our center. All patients had a comprehensive rheumatologic history and examination, with imaging by ultrasonography (US) or magnetic resonance imaging (MRI) in most patients. RESULTS: Between October 2018 and February 2021, we recorded 470 patients with AD commencing dupilumab treatment from routine clinical care records. Of 36 patients referred for rheumatologic assessment, we identified 26 patients (14 male, 12 female) with a musculoskeletal syndrome of inflammatory enthesitis, arthritis, and/or tenosynovitis. Clinical findings were confirmed by US and MRI. All patients had very good response to dupilumab treatment, and no specific predictors of musculoskeletal syndrome were noted. Symptoms were mild in 16 patients, moderate in 6 patients, and severe in 4 patients. Receipt of nonsteroidal antiinflammatory drugs or cyclooxygenase 2 inhibitors, reduction of dupilumab dose/frequency, and cessation of dupilumab therapy led to improvement, but moderate or severe symptoms persisted for many months. CONCLUSION: We report a new musculoskeletal syndrome of inflammatory enthesitis/arthritis/tenosynovitis in some patients receiving the IL-4 receptor antagonist dupilumab. This response to a cytokine-targeting therapy provides key insights into the pathogenesis of enthesitis.

Treatment of gangrenous digit-threatening paraneoplastic acrocyanosis with vasodilator therapy.

A man in his 70s, with a recent diagnosis of transitional cell carcinoma of the bladder, reported a 2-month history of discolouration, pain and paraesthesia affecting his fingers. Clinical assessment noted peripheral acrocyanosis with areas of digital ulceration and gangrene. Following further work-up to evaluate potential causes, he was diagnosed with paraneoplastic acrocyanosis. He proceeded to undergo robotic cystoprostatectomy and received adjuvant chemotherapy for the management of his cancer. In parallel to the chemotherapy, vasodilatory therapy was administered as two courses of intravenous synthetic prostacyclin analogue iloprost along with sildenafil. This resulted in a significant improvement in digital pain and gangrene with healing of ulceration.

A data-driven quality-score system for rating drug products and its implications for the health care industry.

The quality of drug products in the United States has been a matter of growing concern. Buyers and payers of pharmaceuticals have limited insight into measures of drug-product quality. Therefore, a quality-score system driven by data collection is proposed to differentiate between the qualities of drug products produced by different manufacturers. The quality scores derived using this proposed system would be based upon public regulatory data and independently-derived chemical data. A workflow for integrating the system into procurement decisions within health care organizations is also suggested. The implementation of such a quality-score system would benefit health care organizations by including the consideration of the quality of products while also considering price as a part of the drug procurement process. Such a system would also benefit the U.S. health care industry by bringing accountability and transparency into the drug supply chain and incentivizing manufacturers to place an increased emphasis on the quality and safety of their drug products.

Prevagen®: Analysis of Clinical Evidence and Its Designation as a "#1 Pharmacist Recommended Brand".

Prevagen® is a dietary supplement that is marketed to help with mild memory loss associated with older people. The manufacturer of the product notes that clinical evidence supports this use. Furthermore, the manufacturer notes that Prevagen® is a "#1 Pharmacist Recommended Brand." The authors' search of the literature identified one clinical study that evaluated the efficacy and safety of Prevagen®; however, this study possesses significant limitations and therefore one must question the merits of such clinical evidence. Prevagen®'s designation as a "#1 Pharmacist Recommended Brand" is based on a survey facilitated by Pharmacy Times® that is designed to identify the brand name over-the-counter products that pharmacists recommend most frequently. Because of the limited clinical data supporting Prevagen®'s efficacy, it is likely that the survey results reflect pharmacists' familiarity with this product, which may be influenced by extensive advertising techniques. As practitioners of evidence-based medicine, pharmacists should not recommend a product with limited evidence to support its use. Furthermore, pharmacists should proactively educate their patients, especially those who are most vulnerable, about the rational use of all pharmacologically active substances, including dietary supplements.

Medical Communications in an Agency Setting: A Career Option for Pharmacists.

Medical communications (MedComms) agencies serve the varied needs of the pharmaceutical industry and other healthcare-related organizations. These agencies present a unique practice opportunity for pharmacists who possess the requisite knowledge and skillset to flourish and grow professionally in this environment. Published information about this sector of the industry is limited. To this end, this article provides an overview of the MedComms agency setting and describes the services provided by such agencies. These include the development of branded and/or unbranded communications materials in the form of publications, oral and video presentations, slide decks, and other materials. MedComms professionals also facilitate and support professional meetings and presentations, such as congresses, symposia, and advisory boards. Other services that MedComms agencies provide include engaging key opinion leaders, providing clinical trial services, and brand identification or positioning. The article describes the opportunities for pharmacists in this field, key characteristics and skills needed to succeed in this industry, and the pathway for pharmacists to enter this field.

Novel Incision-free Device for Transvaginal Apical Pelvic Organ Prolapse Repair.

STUDY OBJECTIVE: The purpose of this study was to present the feasibility and potential clinical advantages of Apyx (Escala Medical, Israel), a minimally invasive incision-free anchoring device, for apical prolapse repair. DESIGN: An experimental prospective animal and cadaver study. SETTING: Animal facility and a cadaver laboratory of a tertiary care teaching hospital. PATIENTS: Included in this study were 7 ovine models, 2 porcine specimens, and 3 fresh unembalmed female human cadavers. INTERVENTIONS: The Apyx device for sacrospinous ligament (SSL) suspension was tested on ovine and porcine models. The pullout force needed to detach the Apyx anchor from the SSL was measured. Safety, reliability, and feasibility of this new incision-free procedure were also tested on an ovine model and human cadavers. The precision in deployment of the Apyx device to the SSL was tested via palpation by the surgeon, tissue dissection, and x-ray imaging. The efficacy was tested both by pullout forces and histologic analysis of the vaginal attachment to the SSL. MEASUREMENTS AND MAIN RESULTS: Forty-two anchors were inserted into the SSLs on ovine and porcine models and on cadaver SSLs. No abnormalities or malfunctions were noted in the functional performance of the anchors or the retrieval device. Mean pullout force for the ovine animal model was 38.64 ± 2.80 N. Pullout force in the porcine model was found to be in correlation with the values observed in the ovine model. None of the measured forces was below 20 N. Accuracy and safety tests showed good consistency when deploying the Apyx device to the SSL with no damage to surrounding organs in the ovine or the human cadaver model. Histology demonstrated biologic adhesion characterized by a gross assessment of a newly formed, firm fibrotic tissue 12 weeks after anchor deployment. CONCLUSION: The Apyx anchoring system, a novel incision-free minimally invasive prolapse repair device, demonstrated an anatomically feasible, easy-to-use procedure for suspending the vaginal apex to the SSLs. Its clinical safety, efficacy, and impact on patient symptoms and quality of life should be further studied.

Survey of drug information centers in the United States-2018.

PURPOSE: To provide a current directory of drug information centers (DICs) in the United States and present information about their characteristics, activities and services, and networking activities. METHODS: In February 2018, an electronic 23-question survey was delivered to 118 contacts on a distribution list compiled from previous directories of DICs, responses to listserv messages, and an Internet search. DICs, defined as formal centers dedicated to providing drug information services, including but not limited to responding to drug information requests, were asked questions about their characteristics, activities and services, drug information requests, and networking activities. RESULTS: The response rate was 79% (93 of 118 DICs). Of the 93 respondents, 82 (88%) met the definition of a DIC and were included in the directory. Of the 82 included DICs, 37 (45%) belonged to a university or college, while 36 (44%) belonged to a medical center or hospital. Seventy percent of the DICs (n = 57) had been in existence for more than 20 years. Of the 81 respondents reporting activities performed at the DICs, precepting pharmacy students (n = 79, 98%) and training pharmacy residents and/or fellows (n = 68, 84%) were most commonly reported. Nearly 90% reported that answering drug information questions was central to the DIC operations. Most DICs (n = 52, 65%) indicated receiving an average of 50 requests or less on a monthly basis. DICs reported a variety of electronic means of communicating with the DIC community, although 16 (21%) of the 77 respondents reported no need to do so. CONCLUSION: The survey identified 82 DICs that collectively provide a variety of services to their clienteles. The DIC directory published herein should facilitate networking among DICs.

Meiotic drive reduces egg-to-adult viability in stalk-eyed flies.

A number of species are affected by Sex-Ratio (SR) meiotic drive, a selfish genetic element located on the X-chromosome that causes dysfunction of Y-bearing sperm. SR is transmitted to up to 100% of offspring, causing extreme sex ratio bias. SR in several species is found in a stable polymorphism at a moderate frequency, suggesting there must be strong frequency-dependent selection resisting its spread. We investigate the effect of SR on female and male egg-to-adult viability in the Malaysian stalk-eyed fly, Teleopsis dalmanni. SR meiotic drive in this species is old, and appears to be broadly stable at a moderate (approx. 20%) frequency. We use large-scale controlled crosses to estimate the strength of selection acting against SR in female and male carriers. We find that SR reduces the egg-to-adult viability of both sexes. In females, homozygous females experience greater reduction in viability (sf = 0.242) and the deleterious effects of SR are additive (h = 0.511). The male deficit in viability (sm = 0.214) is not different from that in homozygous females. The evidence does not support the expectation that deleterious side effects of SR are recessive or sex-limited. We discuss how these reductions in egg-to-adult survival, as well as other forms of selection acting on SR, may maintain the SR polymorphism in this species.

Clinical and other specialty services offered by pharmacists in the community: the international arena and Israel.

The community pharmacy setting is a venue that is readily accessible to the public. In addition, it is staffed by a pharmacist, who is a healthcare provider, trained and capable of delivering comprehensive pharmaceutical care. As such, community pharmacists have a colossal opportunity to serve as key contributors to patients' health by ensuring appropriate use of medications, preventing medication misadventures, identifying drug-therapy needs, as well as by being involved in disease management, screening, and prevention programs. This unique position gives the pharmacist the privilege and duty to serve patients in roles other than solely that of the stereotypical drug dispenser.Worldwide, as well as in Israel, pharmacists already offer a variety of pharmaceutical services and tend to patients' and the healthcare system's needs. This article provides examples of professional, clinical or other specialty services offered by community pharmacists around the world and in Israel and describes these interventions as well as the evidence for their efficacy. Examples of such activities which were recently introduced to the Israeli pharmacy landscape due to legislative changes which expanded the pharmacist's scope of practice include emergency supply of medications, pharmacists prescribing, and influenza vaccination. Despite the progress already made, further expansion of these opportunities is warranted but challenging. Independent prescribing, as practiced in the United Kingdom or collaborative drug therapy management programs, as practiced in the United States, expansion of vaccination programs, or wide-spread recognition and reimbursement for medication therapy management (MTM) programs are unrealized opportunities. Obstacles such as time constraints, lack of financial incentives, inadequate facilities and technology, and lack of professional buy-in, and suggested means for overcoming these challenges are also discussed.

Hypermobility and sports injury.

OBJECTIVE: To determine whether there is an association between hypermobility and sports injury. METHODS: A quantitative observational approach using a cross-sectional survey was adopted. Individuals were identified as hypermobile or not. All participants were asked to complete two questionnaires: one asking demographic information and the other injury-specific. Fisher's exact test was used for statistical analysis. RESULTS: 114 individuals participated in the study, 62 women and 52 men. 26% of the participants were hypermobile. There was no significant association between hypermobility and sports injury (p=0.66). There was a significant increase in joint and ligament sprain among the non-hypermobile (NH) group covering all sports (p=0.03). Joint dislocation was found exclusively among hypermobile individuals. The duration of injury in hypermobile individuals was higher than NH. The use of oral painkillers or anti-inflammatories in the semiprofessional group was greater than the general population. CONCLUSION: Hypermobility is relatively common among individuals, and there is a lot of anecdotal evidence associating it with increased rates of injuries. This project finds that NH individuals are more likely to sustain a ligament or joint sprain in sports. This is due to increased joint laxity and flexibility preventing injury. There were important limitations to this study which will be addressed in further work. These include assessing for pauciarticular hypermobility and focusing on one sport to investigate its association with sports injury in those who are hypermobile or not. It would also be important to focus on one specific joint, assessing its flexibility and association with injury.

Prevalence and characteristics of pharmacies owned and operated by schools of pharmacy in the United States.

INTRODUCTION: To identify schools/colleges of pharmacy that own and operate a pharmacy and to gather key details about such pharmacies. METHODS: Schools of pharmacy (n = 134) in the United States were contacted to determine whether they own and operate a pharmacy. Schools identified as having a pharmacy were subsequently sent an online questionnaire to solicit information about school and pharmacy characteristics. RESULTS: Eighteen (13.4%) schools reported owning and operating at least one pharmacy; of these, 14 (77.8%) responded to the questionnaire. The provision of education was a goal for all pharmacies. Pharmacy services were provided to students, faculty/staff, and community members (85.7%, 78.6%, and 50%, respectively). Student pharmacists were regularly involved in the operations of 13 (92.9%) pharmacies, largely as part of their introductory and advanced pharmacy practice experiences and/or as paid employees. CONCLUSION: Few schools of pharmacy in the United States own and operate a pharmacy. These pharmacies primarily serve as teaching and learning venues and provide services to the campus community and/or the community at large.

Bioinspired, Spine-Like, Flexible, Rechargeable Lithium-Ion Batteries with High Energy Density.

The rapid development of flexible and wearable electronics proposes the persistent requirements of high-performance flexible batteries. Much progress has been achieved recently, but how to obtain remarkable flexibility and high energy density simultaneously remains a great challenge. Here, a facile and scalable approach to fabricate spine-like flexible lithium-ion batteries is reported. A thick, rigid segment to store energy through winding the electrodes corresponds to the vertebra of animals, while a thin, unwound, and flexible part acts as marrow to interconnect all vertebra-like stacks together, providing excellent flexibility for the whole battery. As the volume of the rigid electrode part is significantly larger than the flexible interconnection, the energy density of such a flexible battery can be over 85% of that in conventional packing. A nonoptimized flexible cell with an energy density of 242 Wh L-1 is demonstrated with packaging considered, which is 86.1% of a standard prismatic cell using the same components. The cell also successfully survives a harsh dynamic mechanical load test due to this rational bioinspired design. Mechanical simulation results uncover the underlying mechanism: the maximum strain in the reported design (≈0.08%) is markedly smaller than traditional stacked cells (≈1.1%). This new approach offers great promise for applications in flexible devices.

Pharmacovigilance in Israel - tools, processes, and actions.

BACKGROUND: Due to the limited safety data available at the time that a new medication is first marketed, it is essential to continue the collection and monitoring of safety data about adverse drug reactions (ADRs) during the medication's life cycle. This activity, known as pharmacovigilance (PV), is performed worldwide by the pharmaceutical industry as well as by regulatory agencies. In 2012, the Israeli Ministry of Health (MOH) established a Pharmacovigilance and Drug Information Department. The Department is tasked with identifying, monitoring, and initiating activities aimed at minimizing risks associated with medication utilization. To enable this, the MOH has devised procedures for PV and promoted extensive legislation in this area that require marketing authorization holders (MAHs) and medical institutions in Israel to report ADRs and new safety information to the MOH. A computerized database was created to support the reporting process. The objective of this article is to characterize the PV tools and activities implemented in Israel. METHODS: Since September 2014, The Israeli Pharmacovigilance and Drug Information Department receives ICSRs at a central computerized database developed for this purpose. The data were analyzed by Department personnel and ICSRs were characterized according to their seriousness, source, categories of drugs involved, and the reporting format. Additionally, the Department reviewed signals detected from ADR reports and from other sources and assessed the resulting regulatory actions. RESULTS: An analysis of the Individual Case Safety Reports (ICSRs) submitted to the MOH's ADRs central database reveals that during the review period, a total of 16,409 ICSRs were received by the Department and 850 signals were identified, resulting in the following PV activities: inquiry and enhanced follow-up (430, 50.6%), prescriber's and patient's leaflets updates (204, 24%), recall of products/batches (6, 0.7%), alerts for health care professionals (63, 7.4%). Eighty five (10%) of the signals required a comprehensive investigation involving external specialist and 1 (0.1%) resulted in initiation of epidemiologic study. Additionally, in 2015 the Department incorporated comprehensive framework for risk minimization of marketed medicinal products, also known as risk management plans (RMPs). CONCLUSIONS: As practiced by other health authorities, the Israeli MOH effectively implemented various PV tools to ensure the safety of the Israeli health consumer.

Improved long-term survival with contralateral prophylactic mastectomy among young women.

BACKGROUND: Despite mixed survival data, the utilization of contralateral prophylactic mastectomy (CPM) for the prevention of a contralateral breast cancer (CBC) has increased significantly over the last 15 years, especially among women less than 40. We set out to look at our own experience with CPM, focusing on outcomes in women less than 40, the sub-population with the highest cumulative lifetime risk of developing CBC. With an extended follow-up, we hoped to demonstrate differences in the long-term disease free survival (DFS) and overall survival (OS) among groups who underwent the procedure (CPM) versus those that did not (NCPM). MATERIALS AND METHODS: We performed a retrospective review of all breast cancer patients less than age 40 diagnosed at Mount Sinai Medical Center between January 1, 1980 and December 31, 2010 (n=481). Among these patients, 42 were identified as having undergone CPM, while 195 were confirmed as being CPM-free during the observation period. A univariate and multivariate analyses were performed. RESULTS: The CPM group had a significantly higher percentage of patients who were diagnosed between 2000 and 2010 (95.2% vs 40%, p=0.0001). The CPM group had significantly smaller tumors (0-2cm.: 41.7% vs 24.8%, p=0.04). Among the entire group of patients, the overall five- and 10-year DFS were 81.3% and 73.3%, respectively. CPM was significantly associated [HR 2.35 (1.02, 5.41); p=0.046] with 10-year OS, although a similar effect was not observed for five-year OS. CONCLUSIONS: We found that CPM has increased dramatically over the last 15 years, especially among white women with locally advanced disease. In patients less than 40, who are thought to be at greatest cumulative risk of secondary breast cancer, CPM provided an OS advantage, regardless of genetics, tumor or patient characteristics, and which was only seen after 10 years of follow-up.

Drug information--the systematic approach: continuing education article.

Proper drug information (DI) skills are essential for being a competent pharmacy practitioner. To effectively manage DI queries and clinical dilemmas, the practitioner should follow a systematic approach that includes identifying the requester, determining the "true" DI need and obtaining background information, categorizing the question, performing the search and analyzing the information, disseminating the information, and following up when appropriate. The practitioner must be mindful to couple the published literature with clinical experience, knowledge, and logic in order to achieve optimal clinical outcomes.