Citations

The following describes a case of isolated visceral angioedema related to an angiotensin II receptor blocker (ARB) medication. Additionally, we discuss the pathophysiology of drug-induced angioedema, various presentations that can be encountered, and the leading theorized mechanisms of how renin-angiotensin-aldosterone system (RAAS) blocking medications lead to angioedema. The goal of sharing this case is to help increase awareness of the possibility of ARB-induced angioedema and to recommend keeping visceral angioedema as part of the differential diagnosis when presented with a patient who is taking an angiotensin converting enzyme inhibitor (ACEI) or ARB medication that is experiencing gastrointestinal symptoms of unclear etiology.

The Pharmacogene Variation Consortium (PharmVar) provides nomenclature for the highly polymorphic human CYP2D6 gene locus and a comprehensive summary of structural variation. CYP2D6 contributes to the metabolism of numerous drugs and, thus, genetic variation in its gene impacts drug efficacy and safety. To accurately predict a patient's CYP2D6 phenotype, testing must include structural variants including gene deletions, duplications, hybrid genes, and combinations thereof. This tutorial offers a comprehensive overview of CYP2D6 structural variation, terms, and definitions, a review of methods suitable for their detection and characterization, and practical examples to address the lack of standards to describe CYP2D6 structural variants or any other pharmacogene. This PharmVar tutorial offers practical guidance on how to detect the many, often complex, structural variants, as well as recommends terms and definitions for clinical and research reporting. Uniform reporting is not only essential for electronic health record‐keeping but also for accurate translation of a patient's genotype into phenotype which is typically utilized to guide drug therapy.

Pembrolizumab is an immune checkpoint inhibitor used in many cancer types, including genitourinary cancers. Although immunotherapies have dramatically changed the landscape of cancer treatment by providing an alternative to traditional chemotherapy, they have been associated with significant immune-related adverse events (IRAEs) with wide-ranging clinical manifestations. We present the case of an elderly woman on pembrolizumab for metastatic bladder cancer who developed cutaneous IRAE with lichenoid eruptions that responded to high-dose intravenous glucocorticoids.

Cryptococcal species endocarditis is infrequently described, carries high mortality and nearly always occurs in immunocompromised states or on prosthetic valves. We report the case of a man in his 70s with multiple recent hospitalisations for pneumonia, hypercalcaemia and septic tank exposure who presented with intermittent fevers, progressive weakness,and worsening encephalopathy, manifested as confusion and word-finding difficulties for 3 weeks. Workup revealed cryptococcal species on blood serum gram stain, native aortic valve endocarditis and meningitis. Cerebrospinal fluid analysis demonstrated lymphocytosis, ultimately found to be secondary to chronic lymphocytic leukaemia. Surgical valve replacement was deemed medically contraindicated and antifungal therapy was initiated. Though poorly understood with very few documented cases, management of cryptococcal endocarditis relies on prompt diagnosis, early surgery when indicated, long-term antifungal therapy and treatment of underlying immunocompromising states where possible.

In 2019, there were multiple outbreaks of measles in the United States. In the context of the public awareness of these outbreaks, we performed an intervention with the intent to improve the rate of measles immunization in our pediatric population. Pediatric patients that were lacking adequate measles immunization were identified by electronic medical record (EMR) survey. Charts were reviewed and updated if records were found to be incomplete. Parents of the remaining children were sent a letter, personally signed by the child’s primary care provider, encouraging measles immunization. A measles fact sheet, produced by the United States Center for Disease Control, was also included with the letter. There were 44 patients in the study group whose parents received a letter and measles fact sheet. As a result, 5 of these children were brought in for a measles, mumps, and rubella (MMR) immunization. The 44 patients whose parents received a letter included 20 patients whose parents had previously expressed intent to not vaccinate their children as documented in the EMR. None of these children received an MMR immunization. Although small in scope, this project provides a glimpse into the importance of personal provider guidance to parents who are inclined to immunize their children. Unfortunately, it also demonstrated that provider advice did not change the opinions of parents who had already taken a stance against vaccination, even in the context of an urgent public health situation that had garnered widespread coverage in the lay press and social media.

Gynecomastia is benign enlargement of glandular tissue in the male breast. It occurs due to an imbalance of estrogen and testosterone. It may be unilateral or bilateral. Physiologic gynecomastia commonly occurs in infants and during puberty and is self-limited. Gynecomastia may affect up to 50% of adult men over age 50 years old and can be related to underlying medical illness or caused by certain medications. Known causative agents include anti-androgenic and estrogenic drugs. Probable agents include alcohol and anti-ulcer, psychoactive, and antiretroviral medications. Non-steroidal anti-inflammatory drugs (NSAIDs) are not commonly associated with the development of gynecomastia. This case presents an instance in which the NSAID, meloxicam, was the only identified variable in a patient who developed unilateral gynecomastia. His breast tenderness and abnormal exam resolved spontaneously within 4 weeks of cessation of meloxicam therapy.

Background While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. Methods In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. Results GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. Conclusions GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future.

Background Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. Methods We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). Findings In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). Interpretation Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.