Sparsentan: A First-in-Class Dual Endothelin and Angiotensin II Receptor Antagonist.

OBJECTIVE: To provide an overview of the guidelines on the management of immunoglobulin A nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS), review the evidence for sparsentan, and discuss its place in therapy. DATA SOURCES: A literature search was conducted using MEDLINE, EMBASE, and clinicaltrials.gov using the search terms "sparsentan" and "RE-021" up to the end of Jun 2023. STUDY SELECTION AND DATA EXTRACTION: English studies were included if they evaluated the pharmacology, pharmacokinetics, efficacy, and safety of sparsentan in human subjects. Information from the Food and Drug Administration (FDA) and manufacturer's monograph were also extracted. DATA SYNTHESIS: In comparison with irbesartan, sparsentan reduced urine protein-to-creatinine ratio (UPCR) in both IgAN (-49.8% vs -15.1% at interim 36 weeks) and FSGS (-44.8% vs -18.5% at 8 weeks). Hypotension and edema were the most common adverse events in the sparsentan groups. Hepatotoxicity appears to be comparable between sparsentan and irbesartan in short-term results. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON WITH EXISTING DRUGS: Sparsentan provides a new option for patients with IgAN who are otherwise at high risk of progressive kidney disease. Continued FDA approval is dependent on long-term study results on renal function decline and safety. CONCLUSION: Sparsentan reduces proteinuria in IgAN and FSGS, and has expedited approval by the FDA for IgAN in patients at risk of rapid disease progression, generally at urine protein-to-creatinine ratio (UPCR) ≥1.5 g/g. Interim results from PROTECT and results from DUET showed promise for improving proteinuria in IgAN and FSGS. Long-term renal function benefit and safety data are pending.

Patterns of natural health product use at an outpatient heart function clinic.

Background: Natural health product (NHP) use is common among Canadians, but the NHPs used by outpatients with cardiovascular conditions such as atrial fibrillation and heart failure have not been identified. Objectives: Describe NHP use among outpatient cardiac patients, assess drug interactions and their potential implications and determine NHP documentation by health care providers. Methods: Telephone interviews were conducted by the main researcher with patients who attended the Cardiac Clinics at the Royal Columbian Hospital. Medication reconciliation was performed to elicit information regarding NHP use and clinic charts were used to supplement demographic information. Results: There were 119 successful interviews. Most patients were approximately 65 years old and male, were diagnosed with atrial fibrillation, had 2 to 3 queried comorbidities and took 2 cardiovascular medications. It was found that 62% of patients use NHPs, and 239 individual NHPs were identified. The most common NHPs used were vitamins and minerals (63%), especially vitamin D (13%), multivitamins (8%) and omega-3s (8%). Interactions between cardiac medications and NHPs occurred in 86% of patients. NHP use was completely documented by health care providers in 24% of patients. Conclusion: NHP use is common among patients who attend outpatient cardiac clinics. Interactions between NHPs and cardiovascular medications are prevalent and may carry specific individual patient risks. NHP documentation by health care providers is often incomplete.

Antibiotics Utilization for Community Acquired Pneumonia in a Community Hospital Emergency Department.

BACKGROUND: A local health authority in Canada implemented its own Antimicrobial Stewardship Program (ASP) which provide guidelines to clinicians to utilize when treating infectious diseases such as community-acquired pneumonia (CAP). Objectives: The primary objective is to describe antibiotic usage patterns at the community hospital's emergency department (ED) and to analyze the patterns in relation to ASP goals of reducing risk of infections, adverse drug events and antibiotic resistance, and to identify potential areas of improvement. METHODS: This retrospective chart review included 156 adult patients with a diagnosis of CAP admitted to a community hospital ED from December 1, 2015 to November 30, 2016. RESULTS: 50.6% patients were prescribed moxifloxacin across all severity of CAP patients. Low and moderate severity CAP patients were most often prescribed antibiotic duration > 7 days. In low, moderate and high severity CAP patients who were treated using ceftriaxone, 100%, 88.9% and 66.6% patients were treated with ceftriaxone 2000 mg daily respectively. CONCLUSIONS: Antibiotic prescribing patterns suggest fluoroquinolones were frequently being over-prescribed, ceftriaxone dosages were often too high, and duration of antibiotics for low and moderate severity CAP were too long. More efforts are needed to promote appropriate antibiotic usage and optimize patient care.

Melatonin for delirium prevention in acute medically ill, and perioperative geriatric patients.

Delirium is a challenging neuropsychiatric ailment that has a negative impact on morbidity and mortality and is difficult to treat once it has developed. The purpose of this review was to analyze the efficacy of melatonin in the prevention of delirium in hospitalized geriatric patients in the acute medically ill and perioperative wards. The databases searched included PubMed (1946 to February 12, 2020), CINAHL (1982 to February 12, 2020), EMBASE (1974 to February 12, 2020), and Web of Science (1900 to February 12, 2020) using search terms related to melatonin, delirium, and prevention. Meta-analyses, randomized controlled trials, and observational studies were included. We excluded publications pertaining to the intensive care unit or oncology, case reports/series, and those not in English. Seven full-text publications were included for qualitative analysis. Patient comorbidities, patient medications, melatonin dosing, dosing regimens, and duration of treatment varied between the studies, which yielded heterogeneous results. Overall, this literature review yielded four studies that showed positive results and three that showed negative results for delirium prevention. The current data for the use of melatonin in delirium is conflicting. This area requires further research of more homogeneous studies with larger sample sizes.

A Case Report of Tadalafil-Associated Fixed Drug Eruption.

Tadalafil is a drug approved for use in erectile dysfunction, but increasingly being used recreationally. There have only been scant case reports on tadalafil causing fixed drug eruption (FDE). Patients who use tadalafil recreationally are less likely to seek medical attention and the diagnosis can often be missed, given the difficulty in diagnosis. However, clinical examination together with a detailed medication history can provide clinicians with good evidence of the association without invasive biopsies. We discuss a 37-year-old male who developed FDE after 2 separate exposures to tadalafil used for recreational purpose. The scar from the first reaction served as a landmark for the second exposure. His lesions resolved 2 days after the initial presentation. The Naranjo adverse drug reaction probability scale (score = 9) indicates a definite adverse drug reaction to tadalafil. We hope to raise awareness of this drug reaction with this case report.

Iatrogenic Opioid Withdrawal in Critically Ill Patients: A Review of Assessment Tools and Management.

OBJECTIVE: To (1) provide an overview of the epidemiology, clinical presentation, and risk factors of iatrogenic opioid withdrawal in critically ill patients and (2) conduct a literature review of assessment and management of iatrogenic opioid withdrawal in critically ill patients. DATA SOURCES: We searched MEDLINE (1946-June 2017), EMBASE (1974-June 2017), and CINAHL (1982-June 2017) with the terms opioid withdrawal, opioid, opiate, critical care, critically ill, assessment tool, scale, taper, weaning, and management. Reference list of identified literature was searched for additional references as well as www.clinicaltrials.gov . STUDY SELECTION AND DATA EXTRACTION: We restricted articles to those in English and dealing with humans. DATA SYNTHESIS: We identified 2 validated pediatric critically ill opioid withdrawal assessment tools: (1) Withdrawal Assessment Tool-Version 1 (WAT-1) and (2) Sophia Observation Withdrawal Symptoms Scale (SOS). Neither tool differentiated between opioid and benzodiazepine withdrawal. WAT-1 was evaluated in critically ill adults but not found to be valid. No other adult tool was identified. For management, we identified 5 randomized controlled trials, 2 prospective studies, and 2 systematic reviews. Most studies were small and only 2 studies utilized a validated assessment tool. Enteral methadone, α-2 agonists, and protocolized weaning were studied. CONCLUSION: We identified 2 validated assessment tools for pediatric intensive care unit patients; no valid tool for adults. Management strategies tested in small trials included methadone, α-2 agonists, and protocolized sedation/weaning. We challenge researchers to create validated tools assessing specifically for opioid withdrawal in critically ill children and adults to direct management.