Clinical Therapeutics

PURPOSE: L-carnitine supplementation has been recommended to improve cardiometabolic health markers in diabetic patients. Our purpose was to assess the dose-dependent effects of l-carnitine supplementation on cardiometabolic risk factors in patients with type 2 diabetes. METHODS: PubMed/Medline, Scopus, and Web of Science were searched until May 2022 for randomized controlled trials that examined the impact of l-carnitine supplementation on cardiometabolic risk factors in adults with type 2 diabetes...

PURPOSE: While intravenous (IV) insulin is often administered at a fixed dose of 10 units for acute hyperkalemia, optimal dosing for minimizing hypoglycemia while effectively reversing hyperkalemia has not been established. The purpose of this analysis was to evaluate the effect of insulin dosing strategies on hypoglycemia in patients with hyperkalemia. METHODS: Adult patients presenting to an academic medical center who received IV insulin for hyperkalemia between 2016 and 2020 were retrospectively identified...

PURPOSE: To compare the effect of early vs delayed metformin treatment for glycaemic management among patients with incident diabetes. METHODS: Cohort study using electronic health records of regular patients (1+ visits per year in 3 consecutive years) aged 40+ years with 'incident' diabetes attending Australian general practices (MedicineInsight, 2011-2018). Patients with incident diabetes were defined as those who had a) 12+ months of medical data before the first recording of a diabetes diagnosis AND b) a diagnosis of 'diabetes' recorded at least twice in their electronic medical records or a diagnosis of 'diabetes' recorded only once combined with at least 1 abnormal glycaemic result (i...

PURPOSE: This study aimed to explore the pharmacogenetic variability associated with the pharmacokinetics (PK) and pharmacodynamics (PD) of rivaroxaban in healthy Chinese subjects. METHODS: This was a multicenter study that included 304 healthy adults aged 18 to 45 years with unknown genotypes. All participants were administered a single dose of rivaroxaban at 10 mg, 15 mg, or 20 mg. PK and PD parameters were measured, and exome-wide association analysis was conducted...

PURPOSE: Urinary tract infection (UTI) is the second most common indication for antibiotic therapy among inpatients in the United States. Ceftriaxone, a third-generation cephalosporin, is habitually chosen to treat inpatient UTIs due to familiarity, cost, and perceived safety. However, third-generation cephalosporins increase the risk of health care facility-onset Clostridioides difficile infection (HOCDI) more than any other antibiotic group, while no statistical risk exists for first-generation cephalosporins...

No abstract text is available yet for this article.

There is growing interest in exploiting the advances in artificial intelligence and machine learning (ML) for improving and monitoring antimicrobial prescriptions in line with antimicrobial stewardship principles. Against this background, the concepts of interpretability and explainability are becoming increasingly essential to understanding how ML algorithms could predict antimicrobial resistance or recommend specific therapeutic agents, to avoid unintended biases related to the "black box" nature of complex models...

PURPOSE: Hypertrophic cardiomyopathy (HCM) is an under-recognized genetic cardiac disorder affecting the muscles and contractility of the heart, which in turn can result in heart failure symptoms, arrhythmia, and sudden cardiac death. Previously, pharmacotherapy options for HCM were not disease-specific, often poorly tolerated, and overall inadequate for optimal management. This narrative review discusses the pharmacology of the novel drug mavacamten, the clinical trials supporting its use, and considerations for its use in clinical practice...

No abstract text is available yet for this article.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is a major public health concern. Exacerbation of COPD leads to poor health and frequent episodes of increased systemic and airway inflammation. Immunomodulatory drugs have garnered extensive attention because they may reduce the rate of COPD exacerbation. This review aimed to evaluate the efficacy and safety of nemiralisib in COPD patients. METHODS: Medical databases, including the Cochrane Library, EMBASE, and PubMed, were queried from inception to June 2023 to identify randomized controlled trials (RCTs) on the efficacy of nemiralisib in COPD patients...

PURPOSE: Coagulase-negative staphylococci (CoNS) are Gram-positive organisms that are a known component of normal skin flora and the most common cause of nosocomial bacteremia. For CoNS species, the vancomycin MIC breakpoint for susceptibility set by the Clinical and Laboratory Standards Institute is ≤4 µg/mL. There has been published reports of vancomycin heteroresistance in CoNS with vancomycin MICs of 2 to 4 µg/mL. The aim of this retrospective cohort analysis was to assess the clinical impact of vancomycin MICs <2 µg/mL versus ≥2 µg/mL in adult patients with CoNS bloodstream infections...

PURPOSE: Metronidazole, a widely used antimicrobial medication, has been linked to neurologic adverse drug reactions. This study investigates the association between metronidazole use and first-time neurologic events. METHODS: We conducted a case-time-control study using data from the Danish National Patient Register and the National Prescription Register in years 2013 to 2021. Patients with a first-time diagnosis of encephalopathy, cerebellar dysfunction, or peripheral neuropathy were included...

PURPOSE: NV-5138 ([S]-2-amino-5,5-difluoro-4,4-dimethylpentanoic acid) is an orally bioavailable, small-molecule activator of the mechanistic target of rapamycin complex 1 (mTORC1) pathway in development for treatment-resistant depression. The authors established a model to describe the relationship between plasma and cerebrospinal fluid (CSF) concentrations of NV-5138 and between CSF concentrations and potential biomarkers thought to be associated with mTORC1 activity (ie, orotic acid, N-acetylmethionine, and N-formylmethionine)...

PURPOSE: The bad bitter taste of some medicines is a barrier to overcoming noncompliance with medication use, especially life-saving drugs given to children and the elderly. Here, we evaluated a new class of bitter blockers (thiazolidinediones, TZDs). METHODS: In this study, 2 TZDs were tested, rosiglitazone (ROSI) and a simpler form of TZD, using a high-potency sweetener as a positive control (neohesperidin dihydrochalcone, NHDC). We tested bitter-blocking effects using the bitter drugs tenofovir alafenamide fumarate (TAF), a treatment for HIV and hepatitis B infection, and praziquantel (PRAZ), a treatment for schistosomiasis, by conducting taste testing with 2 separate taste panels: a general panel (N = 97, 20-23 years, 82...

PURPOSE: Spinal muscular atrophy (SMA) is a genetic neuromuscular disease causing progressive muscle weakness and reducing life expectancy. Risdiplam (Evrysdi; Genentech/F. Hoffmann-La Roche Ltd, Basel, Switzerland) is a drug approved for use in the treatment of patients with SMA. The ongoing global risdiplam Compassionate Use Program (CUP), initiated in November 2019, is the largest CUP in SMA, currently providing access to risdiplam for >2000 patients with type 1 or 2 SMA in 59 countries...

No abstract text is available yet for this article.

PURPOSE: Warfarin is effective therapy to prevent thromboembolic complications of venous thromboembolism, atrial fibrillation, and cardiac thrombus, among valvular heart diseases, including in patients treated with prostheses and/or repair. Its optimum effect is achieved when the international normalized ratio (INR) is in the target therapeutic range, but a subtherapeutic level increases risk of thromboembolism and complications. This study aimed to assess the attainment of target therapeutic range, proportion, and factors associated with subtherapeutic level of warfarin...

PURPOSE: Consensus guidelines for hospitalized, non-severe community-acquired pneumonia (CAP) recommend empiric macrolide + β-lactam or respiratory fluoroquinolone monotherapy in patients with no risk factors for resistant organisms. In patients with allergies or contraindications, doxycycline + β-lactam is a recommended alternative. The purpose of this study was to compare differences in outcomes among guideline-recommended regimens in this population. METHODS: This retrospective, multicenter cohort study included patients ≥18 years of age with CAP who received respiratory fluoroquinolone monotherapy, empiric macrolide + β-lactam, or doxycycline + β-lactam...

PURPOSE: Data on the real-life use of amphotericin B lipid complex (ABLC) compared with other available formulations are limited. This study aimed to evaluate the effectiveness, tolerability, and safety of different amphotericin B (AMB) intravenously administered in the context of hospital practice for the treatment of invasive fungal infections (IFI) and to provide new insights into the profile of ABLC. METHODS: This is a multicenter, retrospective, observational study conducted at 10 tertiary Brazilian hospitals...

PURPOSE: Lacosamide (LCM) is a new-generation anti-seizure medication that is efficacious in patients with focal seizures with or without secondary generalization. Until now, the efficacy, safety, and tolerability of LCM are still lacking in Chinese epilepsy patients, particularly for pediatric populations and patients with renal or hepatic impairment. METHODS: This study was conducted to develop a physiologically based pharmacokinetic (PBPK) model to characterize the pharmacokinetics of LCM in Chinese populations and predict the pharmacokinetics of LCM in Chinese pediatric populations and patients with renal or hepatic impairment...