Amin Mirrafiei, Ahmad Jayedi, Sakineh Shab-Bidar
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...
April 8, 2024: Clinical Therapeutics
Meghan E Cook, Lena K Tran, Jeremy R DeGrado, Afrah Alkazemi, Kaylee K Marino
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...
April 8, 2024: Clinical Therapeutics
Mingyue Zheng, Mumtaz Begum, Carla De Oliveira Bernardo, Nigel Stocks, David Gonzalez-Chica
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...
April 1, 2024: Clinical Therapeutics
Zhiyan Liu, Qiufen Xie, Xia Zhao, Yunlong Tan, Wenping Wang, Yu Cao, Xiaohua Wei, Guangyan Mu, Hanxu Zhang, Shuang Zhou, Xiaobin Wang, Ying Cao, Xin Li, Song Chen, Duanwen Cao, Yimin Cui, Qian Xiang
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...
March 28, 2024: Clinical Therapeutics
Eric Wombwell, Allison Rosa
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...
March 28, 2024: Clinical Therapeutics
Steven Hirschfeld
No abstract text is available yet for this article.
March 22, 2024: Clinical Therapeutics
Daniele Roberto Giacobbe, Cristina Marelli, Sabrina Guastavino, Sara Mora, Nicola Rosso, Alessio Signori, Cristina Campi, Mauro Giacomini, Matteo Bassetti
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...
March 21, 2024: Clinical Therapeutics
J Chase Cole, Samantha F Benvie, Marci DeLosSantos
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...
March 19, 2024: Clinical Therapeutics
Jill L Maron
No abstract text is available yet for this article.
March 18, 2024: Clinical Therapeutics
Hongkuan Yang, Shuifeng He, Linbao Liang, Junjie Pan
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...
March 18, 2024: Clinical Therapeutics
Wade Wheat, Brenda Simiyu, Gabriela Andonie, Lillian Bellfi
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...
March 15, 2024: Clinical Therapeutics
Michael Asger Andersen, Rasmus Gregersen, Tonny Studsgaard Petersen, Joanna Nan Wang, Janne Petersen, Espen Jimenez-Solem
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...
March 15, 2024: Clinical Therapeutics
Azmi Nasser, J Randall Owen, Roberto Gomeni, Alisa R Kosheleff, Jeanelle Portelli, Lilian W Adeojo, Thomas E Hughes
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)...
March 13, 2024: Clinical Therapeutics
Ha Nguyen, Cailu Lin, Ivona Sasimovich, Katherine Bell, Amy Huang, Emilia Leszkowicz, Nancy E Rawson, Danielle R Reed
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...
March 9, 2024: Clinical Therapeutics
Rakesh Kantaria, Karen Baker, Senam Beckley-Kartey, Ksenija Gorni, Isabelle Montrocher-Ober, Laurence Vindevoghel
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...
March 8, 2024: Clinical Therapeutics
Paul Beninger
No abstract text is available yet for this article.
March 7, 2024: Clinical Therapeutics
Abdulkadir Urgessa Jada, Gashahun Mekonnen Disassa, Belete Habte Melesse, Mohammed Mecha Abafogi, Eyob Girma Abera, Kelil Hussein Jibicho, Kedir Negesso Tukeni
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...
February 29, 2024: Clinical Therapeutics
Sidney D Reeves, Aaron P Hartmann, Amanda C Tedder, Paul A Juang, Mikaela Hofer, Marin H Kollef, Scott T Micek, Kevin D Betthauser
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...
February 24, 2024: Clinical Therapeutics
Francelise Bridi Cavassin, Marcello Mihailenko Chaves Magri, Jose Ernesto Vidal, Fabianne Altruda de Moraes Costa Carlesse, Diego Rodrigues Falci, João Luís Baú-Carneiro, Giovanni Luís Breda, Fábio de Araújo Motta, Cássia Silva de Miranda Godoy, Renata de Bastos Ascenço Soares, Carla Sakuma De Oliveira, Ana Verena Almeida Mendes, Hugo Paz Morales, Patrícia Silva Montes, Mariane Taborda, Caroline Martins Rego, Maíra Araujo Félix, Paula Pacheco Katopodis, Julia Raquel da Silva do Ó, Mirela Pereira Lima Abrão, Talita Teles Teixeira Pereira, Flávio Queiroz-Telles
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...
February 24, 2024: Clinical Therapeutics
Gerald Falchook, Amita Patnaik, Debra L Richardson, R Donald Harvey, Manish R Sharma, Navid Hafez, Erika Hamilton, Sarina A Piha-Paul, Minal Barve, Trisha Wise-Draper, Manish R Patel, Afshin Dowlati, Joseph Pascuzzo, Shou-Ching Tang, Christina Faltermeier, Izabela A Malinowska, Luda Shtessel, Alina Striha, Elizabeth Potocka
PURPOSE: The poly (ADP-ribose) polymerase inhibitor niraparib is indicated as maintenance treatment in patients with certain subtypes of advanced ovarian cancer, and is being investigated in patients with other solid tumors. Niraparib is available in 100-mg capsules with a starting dosage of 200 or 300 mg/d. This study assessed the relative bioavailability (BA) and bioequivalence (BE) between a 1 × 300-mg tablet relative to 3 × 100-mg niraparib capsules. In addition, the food effect (FE) of a high-fat meal on the pharmacokinetic (PK) properties of tablet-formulated niraparib was investigated...
March 2024: Clinical Therapeutics
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