Clinical Benefit of Empiric High-dose Levofloxacin Therapy for Adults With Community-onset Enterobacteriaceae Bacteremia.
Abstract PURPOSE: Levofloxacin is commonly prescribed to treat varied community-acquired gram-negative infections; knowledge of the therapeutic efficacies of high-dose (HD) administration is helpful to improve patient care. METHODS: In this 6-year cohort, adults with community-onset Enterobacteriaceae bacteremia were retrospectively studied in 2 hospitals. To overcome the confounding factors in the dosage choice of empiric administration, patients receiving empiric intravenous HD (750 mg/d) therapy were matched with those receiving the conventional dose (CD; 500 mg/d) by using individual propensity ...
Source: Clinical Therapeutics - August 15, 2019 Category: Drugs & Pharmacology Authors: Lee CC, Yang CY, Lee CH, Hsieh CC, Hong MY, Tang HJ, Ko WC Tags: Clin Ther Source Type: research

The Association Between Opioid Use and Outcomes in Infants Undergoing Pyloromyotomy.
Abstract PURPOSE: The purpose of this study was to describe the frequency and variation of opioid use across hospitals in infants undergoing pyloromyotomy and to determine the impact of opioid use on postoperative outcomes. METHODS: A retrospective cohort study (2005-2015) was conducted by using the Pediatric Health Information System (PHIS) database, including infants (aged
Source: Clinical Therapeutics - August 10, 2019 Category: Drugs & Pharmacology Authors: McLaughlin C, Squillaro AI, Ourshaliman S, Song A, Lakshmanan A, Cucchiaro G, Hall M, Burke RV, Kelley-Quon LI Tags: Clin Ther Source Type: research

Colchicine as a Novel Therapy for Suppressing Chemokine Production in Patients With an Acute Coronary Syndrome: A Pilot Study.
tel S Abstract PURPOSE: Existing literature reports that colchicine inhibits inflammasome activation and downstream inflammatory cytokine production and stabilizes coronary plaque. However, colchicine's effect on chemokines, which orchestrate multiple atheroinflammatory pathways, is unknown. METHODS: Patients with acute coronary syndrome (ACS) were randomly assigned to colchicine (1.5 mg PO) (n = 12; mean age, 65.2 years) or no treatment (n = 13; mean age, 62.2 years). Blood samples were collected during cardiac catheterization within 24 hours of colchicine administration from the cor...
Source: Clinical Therapeutics - August 10, 2019 Category: Drugs & Pharmacology Authors: Tucker B, Kurup R, Barraclough J, Henriquez R, Cartland S, Arnott C, Misra A, Martínez G, Kavurma M, Patel S Tags: Clin Ther Source Type: research

Recurrent Thrombosis With Direct Oral Anticoagulants in Antiphospholipid Syndrome: A Systematic Literature Review and Meta-analysis.
Abstract PURPOSE: The treatment of thrombosis in patients with antiphospholipid syndrome (APS) usually requires long-term anticoagulation with vitamin K antagonists. The effectiveness of direct oral anticoagulants (DOACs) in APS has not been fully addressed. The purpose of this research was to analyze the efficacy (thrombotic event-free time) and tolerability (bleeding events) of DOACs in patients with APS. METHODS: We performed a descriptive analysis of a systematic review of data from patients with APS treated with DOACs reported in the literature, via EMBASE, PubMed, and the European League Against Rheumat...
Source: Clinical Therapeutics - August 9, 2019 Category: Drugs & Pharmacology Authors: Sanchez-Redondo J, Espinosa G, Varillas Delgado D, Cervera R Tags: Clin Ther Source Type: research

Need for Causality Assessment Tool for Drug-Induced Acute Kidney Injury.
PMID: 31405528 [PubMed - as supplied by publisher] (Source: Clinical Therapeutics)
Source: Clinical Therapeutics - August 9, 2019 Category: Drugs & Pharmacology Authors: Duru M, Meydan O, Kaya M, Gulmez SE Tags: Clin Ther Source Type: research

Evaluation of Intranasal Corticosteroid Sensory Attributes and Patient Preference for Fluticasone Furoate for the Treatment of Allergic Rhinitis.
The objective of this literature review was to evaluate product characteristics, sensory attributes, and patient preferences of fluticasone furoate intranasal spray (FFNS) compared with other INCs. METHODS: A narrative literature search for studies evaluating FFNS was performed in MEDLINE and Google Scholar. Key terms included "allergic rhinitis," "anti-allergic agents," "intranasal administration," "fluticasone furoate," and "patient preference." Studies published from 2007 to present were included. Nine trials met the search criteria, each evaluating FFNS versus plac...
Source: Clinical Therapeutics - August 8, 2019 Category: Drugs & Pharmacology Authors: May JR, Dolen WK Tags: Clin Ther Source Type: research

Teaching Basic Knowledge on Substance Use Disorders: the Impact of e-Learning on Health Professionals.
This study is the first evaluation of an online pedagogical tool on SUDs. The positive feedback from participants encourages pursuing development of this e-learning. Used before on-campus courses, it provides an attractive educational option to overcome the usual limitations of online classes. PMID: 31395392 [PubMed - as supplied by publisher] (Source: Clinical Therapeutics)
Source: Clinical Therapeutics - August 5, 2019 Category: Drugs & Pharmacology Authors: Jouanjus E, Lapeyre-Mestre M, Nodot M, Roussin A, Franchitto N, Boyes JP, Nasr N, Oustric S, Dupouy J Tags: Clin Ther Source Type: research

Insulin Glargine U100 Improved Glycemic Control and Reduced Nocturnal Hypoglycemia in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease Stages 3 and 4.
oz M Abstract PURPOSE: Glycemic control in patients with chronic kidney disease (CKD) is particularly hard to achieve because of a slower insulin degradation by the kidney. It might modify the long-acting insulin analogue pharmacokinetics, increasing its time-action and the risk of hypoglycemia. However, because this insulin has no peak action, it might be a more tolerable approach to patients with CKD. This hypothesis remains to be tested, because no study has thus far examined the efficacy and safety profile of long-acting basal analogues in patients with significant loss of renal function. The purpose of this s...
Source: Clinical Therapeutics - August 2, 2019 Category: Drugs & Pharmacology Authors: Betônico CC, Titan SMO, Lira A, Pelaes TS, Correa-Giannella MLC, Nery M, Queiroz M Tags: Clin Ther Source Type: research

Effect of Cefiderocol, a Siderophore Cephalosporin, on QT/QTc Interval in Healthy Adult Subjects.
Abstract PURPOSE: Cefiderocol is a novel siderophore cephalosporin with potent activity against gram-negative bacteria, including multidrug-resistant strains. This Phase I study was conducted to assess the tolerability of single-ascending doses of cefiderocol (part 1) and the effect of cefiderocol on cardiac repolarization, assessed using the electrocardiographic corrected QT interval (QTcF) and other ECG parameters (part 2), in healthy adult subjects. METHODS: Part 1 was a randomized, double-blind, placebo-controlled, single-ascending dose study in healthy adult male and female subjects. Part 2 was a 4-perio...
Source: Clinical Therapeutics - August 1, 2019 Category: Drugs & Pharmacology Authors: Sanabria C, Migoya E, Mason JW, Stanworth SH, Katsube T, Machida M, Narukawa Y, Den Nagata T Tags: Clin Ther Source Type: research

Postpartum Bleeding in Pregnant Women Receiving SSRIs/SNRIs: New Insights From a Descriptive Observational Study and an Analysis of Data from the FAERS Database.
ve; C Abstract PURPOSE: To date, the available data on the relationship between the use of selective serotonin reuptake inhibitors (SSRIs) or the serotonin and norepinephrine reuptake inhibitor (SNRI) venlafaxine and postpartum hemorrhage (PPH) are conflicting and have not been extensively investigated, especially in terms of plasma drug concentrations. We performed data mining of antidepressant-induced PPH reported to the US Food and Drug Administration's Adverse Event Reporting System database, to assess the strength of the potential association between antidepressant pharmacotherapy and PPH in pregnant women. C...
Source: Clinical Therapeutics - July 29, 2019 Category: Drugs & Pharmacology Authors: Perrotta C, Giordano F, Colombo A, Carnovale C, Castiglioni M, Di Bernardo I, Giorgetti F, Pileri P, Clementi E, Viganò C Tags: Clin Ther Source Type: research

Naltrexone Treatment for Pregnant Women With Opioid Use Disorder Compared With Matched Buprenorphine Control Subjects.
Abstract PURPOSE: The use of the opioid antagonist naltrexone (NTX) for pregnant women with opioid use disorder (OUD) remains understudied. The purpose of this pilot study was to examine pregnancy and neonatal outcomes in a cohort of NTX-treated women. METHODS: This single-center, retrospective cohort study included 6 mother-infant dyads taking NTX compared with 13 taking buprenorphine (BUP) between 2017 and 2019. Maternal demographic characteristics, any unprescribed or illicit opioid use per urine toxicology or provider report during the pregnancy or 6 months' postdelivery, delivery outcomes, gestational ag...
Source: Clinical Therapeutics - July 27, 2019 Category: Drugs & Pharmacology Authors: Wachman EM, Saia K, Miller M, Valle E, Shrestha H, Carter G, Werler M, Jones H Tags: Clin Ther Source Type: research

Coadministration of Sublingual Immunotherapy Tablets and Management of Potential Adverse Effects: Austrian, German, and Swiss Expert Recommendations.
Abstract Sublingual immunotherapy (SLIT) is currently available as liquid drops and tablets for treatment of allergic patients. Because several allergens are available and many patients are polyallergic, it is possible to treat patients with multiple clinically relevant allergies by>1 SLIT product. Austrian, German, and Swiss medical experts discussed the available data on allergen uptake at the oral mucosa and recently published data on coadministration of a grass and a ragweed tablet. The experts agreed on a schedule considering data from a North American trial on sequential administration of 2 SLIT-tablets w...
Source: Clinical Therapeutics - July 25, 2019 Category: Drugs & Pharmacology Authors: Sturm GJ, Vogelberg C, Marchon M, Horn A, Vitzthum HG, Memar-Baschi MP, Kleine-Tebbe J Tags: Clin Ther Source Type: research

Artificial Intelligence and Patient-centric Approaches to Advance Pharmaceutical Innovation.
PMID: 31353132 [PubMed - as supplied by publisher] (Source: Clinical Therapeutics)
Source: Clinical Therapeutics - July 25, 2019 Category: Drugs & Pharmacology Authors: Kaitin KI Tags: Clin Ther Source Type: research

Host-Based Diagnostics for Acute Respiratory Infections.
This article examines how host response-based diagnostics for ARIs are being used in clinical practice, as well as new developments in the research pipeline. METHODS: A limited search was conducted of the relevant literature, with emphasis placed on literature published in the last 5 years (2014-2019). FINDINGS: Advances are being made in all areas of host response-based diagnostics for ARIs. Specifically, there has been significant progress made in single protein biomarkers, as well as in various "omics" fields (including proteomics, metabolomics, and transcriptomics) and wearable technologies. There a...
Source: Clinical Therapeutics - July 25, 2019 Category: Drugs & Pharmacology Authors: Ross MH, Zick BL, Tsalik EL Tags: Clin Ther Source Type: research

Short-Term Evidence in Adults of Anorexigenic Drugs Acting in the Central Nervous System: A Meta-Analysis.
Abstract PURPOSE: Obesity is a chronic clinical condition that is considered one of the most serious health problems in the world because it can cause other chronic metabolic disorders. A meta-analysis was conducted to evaluate the safety and efficacy of 4 central-acting drugs, all approved in Brazil's market for weight loss. METHODS: PubMed, EMBASE, and Cochrane library databases were searched from inception until January 2018 to retrieve randomized controlled trials comparing sibutramine, diethylpropion, mazindol, and fenproporex versus placebo in overweight or obese patients. Language was not a restriction...
Source: Clinical Therapeutics - July 24, 2019 Category: Drugs & Pharmacology Authors: Farah D, Fonseca MCM Tags: Clin Ther Source Type: research

Should Clinical Trials Be Terminated Early?
Abstract In many trials, interim analyses are often performed to decide whether the trial should be terminated early, for a variety of reasons. These reasons may include an imbalance in adverse events in one group versus the other(s), a situation in which, given the sample size, it would be impossible to demonstrate superiority of one treatment (futility) or a significant difference between groups. This commentary argues that ending a trial prematurely for the latter reason is fraught with problems and often results in an overestimation of the effect that would have been obtained were the trial allowed to con...
Source: Clinical Therapeutics - July 24, 2019 Category: Drugs & Pharmacology Authors: Streiner DL Tags: Clin Ther Source Type: research

Efficacy and Tolerability of Sufentanil, Dexmedetomidine, or Ketamine Added to Propofol-Based Sedation for Gastrointestinal Endoscopy in Elderly Patients: A Prospective, Randomized, Controlled Trial.
Abstract PURPOSE: To investigate the optimal agent combined with propofol for sedation in elderly patients undergoing gastrointestinal endoscopy. METHODS: A total of 120 elderly patients scheduled for gastrointestinal endoscopy under propofol-based sedation were randomly allocated to receive propofol + saline (control group), propofol + sufentanil 0.1 μg/kg, propofol + dexmedetomidine 0.4 μg/kg, or propofol + ketamine 0.4 mg/kg. Mean arterial pressure, heart rate, pulse oximetry, pressure of end-tidal carbon dioxide, respiratory rate, and Ramsay sed...
Source: Clinical Therapeutics - July 23, 2019 Category: Drugs & Pharmacology Authors: Yin S, Hong J, Sha T, Chen Z, Guo Y, Li C, Liu Y Tags: Clin Ther Source Type: research

Some Thoughts About Artificial Intelligence.
PMID: 31345558 [PubMed - as supplied by publisher] (Source: Clinical Therapeutics)
Source: Clinical Therapeutics - July 22, 2019 Category: Drugs & Pharmacology Authors: Shader RI Tags: Clin Ther Source Type: research

Burden of Carcinoid Heart Disease in Patients With Carcinoid Syndrome Initiating Somatostatin Analogues.
This study investigated the prevalence and economic burden of CaHD among adults with CS in the United States. METHODS: This retrospective study analyzed insurance claims of patients with CS initiating somatostatin analogue (SSA) therapy. Eligible patients had ≥1 medical claim for CS with continuous insurance coverage for 1 year before and at least 30 days after initiating SSA therapy. Markers for CaHD were identified using a predetermined list of medical and/or procedural claims based on the clinical experience of a practicing cardiologist. Case subjects had a documented medical/procedural claim for a marker of CaH...
Source: Clinical Therapeutics - July 17, 2019 Category: Drugs & Pharmacology Authors: Joish VN, Perez-Olle R, Lapuerta P, Dharba S, Zacks J Tags: Clin Ther Source Type: research

Myths and Misconceptions: Varicella-Zoster Virus Exposure, Infection Risks, Complications, and Treatments.
Abstract Varicella zoster and herpes zoster are infections caused by the highly contagious varicella-zoster virus (VZV). Despite widespread availability of vaccines against VZV, as well as varicella vaccination rates>95%, VZV remains a public health concern because of several common myths and misconceptions. Because of the success of routine varicella vaccination programs, some people mistakenly believe that varicella and herpes zoster are now no longer a threat to public health. Another common misconception is that shingles is less infectious than varicella; however, clinical evidence indicates otherwise. Seve...
Source: Clinical Therapeutics - July 17, 2019 Category: Drugs & Pharmacology Authors: Newman AM, Jhaveri R Tags: Clin Ther Source Type: research

Lipoprotein(a): Current Evidence for a Physiologic Role and the Effects of Nutraceutical Strategies.
Abstract PURPOSE: Cardiovascular (CV) diseases account for most worldwide mortality, and a higher level of lipoprotein (Lp)-(a) is recognized as a prevalent contributing risk factor. However, there is no consensus regarding nutritional strategies for lowering Lp(a) concentration. Thus, the purposes of this literature review were to: (1) critically examine data concerning the effects of dietetic interventions and nutraceutical agents on Lp(a) level; and (2) review the feasibility and utility of their clinical use. METHODS: A literature search was conducted for studies published between August 2018 and March 20...
Source: Clinical Therapeutics - July 13, 2019 Category: Drugs & Pharmacology Authors: Santos HO, Kones R, Rumana U, Earnest CP, Izidoro LFM, Macedo RCO Tags: Clin Ther Source Type: research

A High-dose Pharmacokinetic Study of a New IgG4 Monoclonal Antibody Temelimab/GNbAC1 Antagonist of an Endogenous Retroviral Protein pHERV-W Env.
Abstract PURPOSE: Temelimab/GNbAC1 is a humanized immunoglobulin G4 monoclonal antibody antagonist of the human endogenous retrovirus W envelope protein, which is associated with multiple sclerosis (MS) pathophysiology and possibly with other autoimmune disorders. Human endogenous retrovirus W envelope protein is expressed in the central nervous system of patients with MS, and sufficient amount of temelimab must reach the target. The safety of very high dosages of temelimab should be tested to support further clinical trials in MS. METHODS: This randomized, placebo-controlled, dose-escalation study evaluated ...
Source: Clinical Therapeutics - July 13, 2019 Category: Drugs & Pharmacology Authors: Porchet H, Vidal V, Kornmann G, Malpass S, Curtin F Tags: Clin Ther Source Type: research

Using Patient Advisory Boards to Solicit Input Into Clinical Trial Design and Execution.
Abstract Academic institutions, pharmaceutical and biotechnology companies, foundations, and associations are routinely implementing patient advisory boards (PABs) to solicit patients' voices and perspectives on a variety of clinical research-related areas, including protocol design, clinical trial execution, informed-consent form design, clinical trial medicine kit design, wearable devices and mobile technologies, and patient-communication materials. Based on experience conducting>50 PABs during the past several years, the authors provide insights into how to best plan and execute PABs and their value in infor...
Source: Clinical Therapeutics - July 12, 2019 Category: Drugs & Pharmacology Authors: Anderson A, Benger J, Getz K Tags: Clin Ther Source Type: research

Efficacy and Safety of a Fixed-Dose Combination of Candesartan and Rosuvastatin on Blood Pressure and Cholesterol in Patients With Hypertension and Hypercholesterolemia: A Multicenter, Randomized, Double-Blind, Parallel Phase III Clinical Study.
This study was a 12-week, randomized, double-blind, placebo-controlled, multicenter study. A total of 394 patients were screened. After a 4-week run-in period, 219 of these patients with hypertension and primary hypercholesterolemia were randomized. Patients received 1 of 3 regimens for 8 weeks: (1) CND 32 mg/RSV 20 mg, (2) RSV 20 mg, or (3) CND 32 mg. The primary outcome variables were changes in the systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the percentage changes in LDL-C from baseline to the drug treatment at 8 weeks. The secondary outcome variables were percentage changes of to...
Source: Clinical Therapeutics - July 12, 2019 Category: Drugs & Pharmacology Authors: Cho KI, Kim BH, Park YH, Ahn JC, Kim SH, Chung WJ, Kim W, Sohn IS, Shin JH, Kim YJ, Chang K, Yu CW, Ahn SH, Kim SY, Ryu JK, Lee JY, Hong BK, Hong TJ, Gyu Park C Tags: Clin Ther Source Type: research

The impact of the opioid epidemic on children and adolescents.
Abstract Although an epidemic of opioid-related overdose deaths has continued to increase in the United States for 2 decades, the impact of opioid use disorders (OUDs) on children and families receives minimal attention. The purpose of this commentary was to provide an overview of the impact of the opioid epidemic on children and adolescents, as well as to summarize challenges to improving outcomes for children. Children and adolescents who grow up in households with opioid misuse and OUDs may experience a myriad of adverse consequences, including: increased risk of mental health problems and drug use; accidental ...
Source: Clinical Therapeutics - July 11, 2019 Category: Drugs & Pharmacology Authors: Winstanley EL, Stover AN Tags: Clin Ther Source Type: research

Apatinib Combined With Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma and Portal Vein Tumor Thrombus: A Multicenter Retrospective Study.
Abstract PURPOSE: Studies focusing on the effects of combined transcatheter arterial chemoembolization (TACE) + the tyrosine kinase inhibitor apatinib in the treatment of patients with hepatocellular carcinoma (HCC), with the location and extent of portal vein tumor thrombus (PVTT) assessed as the main variable, are rare. This multicenter, retrospective, controlled study was performed to compare the efficacy and tolerability of TACE + apatinib and TACE alone in patients with HCC and PVTT. METHODS: We retrospectively analyzed data from patients with nonresectable HCC and PVTT who underwent ...
Source: Clinical Therapeutics - July 11, 2019 Category: Drugs & Pharmacology Authors: Fan W, Yuan G, Fan H, Li F, Wu Y, Zhao Y, Yao W, Wang Y, Xue M, Yang J, Li J Tags: Clin Ther Source Type: research

Effects of an Extract of Salmon Milt on Symptoms and Serum TNF and Substance P in Patients With Fibromyalgia Syndrome.
Abstract PURPOSE: The aim of this study was to evaluate the effects of a dietary supplement containing primarily an extract of salmon's milt (semen) on symptoms and blood levels of proinflammatory molecules in patients with fibromyalgia syndrome (FMS), a chronic, painful musculoskeletal disease without a distinct pathogenesis or treatment. We recently reported increased serum levels of the proinflammatory molecules substance P (SP) and tumor necrosis factor (TNF) in patients with FMS as compared to those in normal controls. METHODS: This prospective, open-label study was conducted in patients with FMS (n ...
Source: Clinical Therapeutics - July 11, 2019 Category: Drugs & Pharmacology Authors: Tsilioni I, Pipis H, Freitag MSC, Izquierdo MDC, Freitag K, Theoharides TC Tags: Clin Ther Source Type: research

Effects of food and calcium carbonate on the pharmacokinetics of lusutrombopag, a novel thrombopoietin receptor agonist.
This report describes 3 studies aimed at assessing the effects of food and calcium carbonate on the pharmacokinetic parameters of lusutrombopag in healthy subjects. METHODS: Three single-dose, open-label crossover studies were conducted. In study 1, eighteen healthy subjects were administered a single 2-mg dose of lusutrombopag as a single tablet in the fasted or fed state or as a 2-mg solution in the fasted state. In study 2, fifteen healthy subjects were administered a single 0.75-mg dose of lusutrombopag as three 0.25-mg tablets in the fasted or fed state, or in the fasted state with coadministration of 4000-mg cal...
Source: Clinical Therapeutics - July 11, 2019 Category: Drugs & Pharmacology Authors: Katsube T, Wajima T, Fukuhara T, Kano T Tags: Clin Ther Source Type: research

Effects of a High-fat Meal on the Pharmacokinetics of the VEGFR Inhibitor Fruquintinib: A Randomized Phase I Study in Healthy Subjects.
The objective of the study was to investigate the tolerability and effect of high-fat food on the pharmacokinetic profile of a fruquintinib capsule in healthy Chinese subjects. METHODS: Healthy Chinese male subjects aged between 18 and 45 years were enrolled in the study. The study included 2 phases: a dose-escalation phase and a food effect-assessment phase. In the dose-escalation phase, subjects were administered a single dose of fruquintinib (2, 3, or 4 mg) in the fasted state. In the food effect-assessment phase, subjects were administered a 4-mg fruquintinib capsule in the fasted and fed states, respectively...
Source: Clinical Therapeutics - July 1, 2019 Category: Drugs & Pharmacology Authors: Qian H, Fan S, Li K, Sai Y, Su W, Chen Q, Liu Y, Li T, Wang W, Jia J, Yu C, Liu Y Tags: Clin Ther Source Type: research

Normal Weight Obesity: An Underrecognized Problem in Individuals of South Asian Descent.
Abstract PURPOSE: Obesity has attained pandemic proportions across the world, and its prevalence in developing countries is also on the rise. Nevertheless, there is still a large gap in understanding the reasons behind a disproportionately high prevalence of diabetes as opposed to a lesser degree of obesity seen in individuals of South Asian origin. This research letter highlights the importance of identifying individuals with normal weight obesity, which may partially bridge this knowledge gap. METHODS: We reviewed recently published evidence on normal weight obesity. FINDINGS: Normal weight obesity is ...
Source: Clinical Therapeutics - July 1, 2019 Category: Drugs & Pharmacology Authors: Kapoor N, Furler J, Paul TV, Thomas N, Oldenburg B Tags: Clin Ther Source Type: research

Bioequivalence and Food Effect of Dapagliflozin/Saxagliptin/Metformin Extended-release Fixed-combination Drug Products Compared With Coadministration of the Individual Components in Healthy Subjects.
This study evaluated the bioequivalence and safety of 2 dapagliflozin/saxagliptin/metformin extended-release (XR) FCDPs relative to their ICs: saxagliptin and dapagliflozin/metformin XR. METHODS: This randomized, open-label, single-dose, single-center crossover study was conducted in 84 healthy subjects aged 18-55 years. The primary objective was to evaluate the fed-state bioequivalence of a dapagliflozin 5-mg/saxagliptin 2.5-mg/metformin 1000-mg XR FCDP and a dapagliflozin 10-mg/saxagliptin 5-mg/metformin 1000-mg XR FCDP relative to the ICs. Secondary objectives included the evaluation of the effect of food on the ph...
Source: Clinical Therapeutics - June 29, 2019 Category: Drugs & Pharmacology Authors: Tang W, Engman H, Zhu Y, Dayton B, Boulton DW Tags: Clin Ther Source Type: research

Corrigendum to "Effectiveness of Delayed-release Dimethyl Fumarate on Clinical and Patient-Reported Outcomes in Patients With Relapsing Multiple Sclerosis Switching From Glatiramer Acetate: RESPOND, a Prospective Observational Study" [Clinical Therapeutics 40 (12) (2018) 2077-2087].
Corrigendum to "Effectiveness of Delayed-release Dimethyl Fumarate on Clinical and Patient-Reported Outcomes in Patients With Relapsing Multiple Sclerosis Switching From Glatiramer Acetate: RESPOND, a Prospective Observational Study" [Clinical Therapeutics 40 (12) (2018) 2077-2087]. Clin Ther. 2019 Jun 26;: Authors: Kresa-Reahl K, Repovic P, Robertson D, Okwuokenye M, Meltzer L, Mendoza JP PMID: 31255296 [PubMed - as supplied by publisher] (Source: Clinical Therapeutics)
Source: Clinical Therapeutics - June 26, 2019 Category: Drugs & Pharmacology Authors: Kresa-Reahl K, Repovic P, Robertson D, Okwuokenye M, Meltzer L, Mendoza JP Tags: Clin Ther Source Type: research

A Study on the Application and Use of Artificial Intelligence to Support Drug Development.
Abstract PURPOSE: The Tufts Center for the Study of Drug Development (CSDD) and the Drug Information Association (DIA) in collaboration with 8 pharmaceutical and biotechnology companies conducted a study examining the adoption and effect of artificial intelligence (AI), such as machine learning, on drug development. The study was conducted to clarify and understand AI adoption across the industry and to gather detailed insights into the spectrum of activities included in the definition of AI. The study investigated and identified analytical platforms and innovations across pharmaceutical and biotechnology companie...
Source: Clinical Therapeutics - June 24, 2019 Category: Drugs & Pharmacology Authors: Lamberti MJ, Wilkinson M, Donzanti BA, Wohlhieter GE, Parikh S, Wilkins RG, Getz K Tags: Clin Ther Source Type: research

Efficacy and Safety of Udenafil for the Treatment of Pulmonary Arterial Hypertension: a Placebo-controlled, Double-blind, Phase IIb Clinical Trial.
Abstract PURPOSE: Udenafil is an oral phosphodiesterase-5 inhibitor approved for the treatment of erectile dysfunction. In a multicenter, placebo-controlled, randomized Phase IIa study, the reduction of pulmonary vascular resistance index was greater with a 50-mg baseline dose of udenafil than with the 100-mg dose, the cardiac index did not decrease at most points, and the safety was excellent, suggesting that 50-mg udenafil could be used in a Phase IIb trial. METHODS: In this 16-week, double-blind, placebo-controlled study, 63 patients with pulmonary arterial hypertension were randomized to receive 50-mg ude...
Source: Clinical Therapeutics - June 12, 2019 Category: Drugs & Pharmacology Authors: Chang HJ, Song S, Chang SA, Kim HK, Jung HO, Choi JH, Lee JS, Kim KH, Jeong JO, Lee JH, Kim DK Tags: Clin Ther Source Type: research

Regulatory Considerations on the Development, Evaluation, and Approval of Therapies in Rheumatoid Arthritis Prevention.
PMID: 31202507 [PubMed - as supplied by publisher] (Source: Clinical Therapeutics)
Source: Clinical Therapeutics - June 12, 2019 Category: Drugs & Pharmacology Authors: Richard C, Hedrick JA Tags: Clin Ther Source Type: research

Comparative Bioavailability Study of a New Orodispersible Formulation of Ibuprofen Versus Two Existing Oral Tablet Formulations in Healthy Male and Female Volunteers.
This study aimed to assess the comparative bioavailability between ibuprofen acid orodispersible tablets (Test product) and ibuprofen acid oral tablets (Reference product). METHODS: This was a randomized, single-dose, 3-way crossover, open-label, pharmacokinetic study in 36 healthy male and female volunteers. Blood samples were taken periodically over a 12-h period after dosing to derive total plasma ibuprofen and S(+)/R(-) ibuprofen enantiomer pharmacokinetic parameters; safety profile and tolerability were evaluated throughout the study. FINDINGS: After a single-dose administration of ibuprofen acid oral tablet...
Source: Clinical Therapeutics - June 12, 2019 Category: Drugs & Pharmacology Authors: Sugár D, Francombe D, da Silva T, Hanid S, Hutchings S Tags: Clin Ther Source Type: research

Hospital-wide Description of Clinical Indications for Anti-infective Use.
This study is the first description of hospital-wide anti-infective use according to clinical indication for a pediatric hospital. Children's Hospital Colorado (CHCO) is uniquely poised to examine its anti-infective use after the implementation of provider-selected order indications (PSOIs), which are distinct from Diagnosis Related Group classifications in that they are used for clinical treatment as opposed to final diagnosis codes for billing and thus are more granular. METHODS: This study used our institution's mandatory PSOIs to describe overall clinical indications for anti-infective use. For 2016, all anti-infe...
Source: Clinical Therapeutics - June 10, 2019 Category: Drugs & Pharmacology Authors: Williams MC, Obermeier H, Hurst AL, Saporta-Keating SR, Pearce K, MacBrayne CE, Child J, Parker SK Tags: Clin Ther Source Type: research

Incidence and Prevalence of Microvascular and Macrovascular Diseases and All-cause Mortality in Type 2 Diabetes Mellitus: A 10-year Study in a US Commercially Insured and Medicare Advantage Population.
Abstract PURPOSE: The relationship between type 2 diabetes mellitus (T2DM) and increased microvascular and macrovascular disease and mortality is well established; however, data for the broad US T2DM population, especially by age, are limited. To help address this issue, we conducted a cohort study in a large national US commercially insured/Medicare Advantage population that incorporated a broad range of different age groups, including a large subset of younger individuals, during a 10-year study period. METHODS: This longitudinal study combined health plan claims and mortality data to identify incident T2DM...
Source: Clinical Therapeutics - June 10, 2019 Category: Drugs & Pharmacology Authors: Visaria J, Iyer NN, Raval A, Kong S, Hobbs T, Bouchard J, Kern DM, Willey V Tags: Clin Ther Source Type: research

Single-Center Analysis of the Potential Inappropriate Use of Intravenous Medications in Hospitalized Patients in China.
This study categorizes the types of inappropriate intravenous prescriptions in hospitalized patients in China. Prescription data from 2016 were retrospectively analyzed based on predefined categories of inappropriateness. Of the 123,521 patients included, 89.2% received intravenous medications, contributing to 80% of the patients' hospital medication costs. Of significant concern, antibiotics and traditional Chinese medicines were administered to 44.3% and 14.5% of hospitalized patients, respectively. Overall, 11.4% of all intravenous prescriptions were classified as inappropriate, with improper diluent and diluent volumes...
Source: Clinical Therapeutics - June 4, 2019 Category: Drugs & Pharmacology Authors: Zeng S, Wang D, Yan Y, Zhu M, Liu W, Gong Z, Wang L, Sun S Tags: Clin Ther Source Type: research

DPP-4 Inhibitor Dose Selection According to Manufacturer Specifications: A Contemporary Experience From UK General Practice.
Abstract Recently, 2 dipeptidyl peptidase-4 (DPP-4) inhibitors, sitagliptin and saxagliptin, adjusted dosing specification from creatinine clearance to glomerular filtration rate, more typically reported in routine laboratory tests. This cross-sectional study examines all DPP-4 inhibitor initiations that require dose adjustment and the dose selection using data from UK general practice. Results indicate that 34% of patients taking a nonlinagliptin DPP-4 inhibitor were given a higher dose and 11% a lower dose than specified in the Summary of Product Characteristics. This reinforces the deviation from Summary o...
Source: Clinical Therapeutics - June 1, 2019 Category: Drugs & Pharmacology Authors: Spanopoulos D, Busse M, Webb J, Tebboth A, Gollop ND, Marcus MW Tags: Clin Ther Source Type: research

Propafenone-associated Gross Hematuria: A Case Report and Review of the Literature.
We present a case report of an 81-year-old patient with propafenone-associated gross hematuria. METHODS: The Naranjo Adverse Drug Reaction Probability Scale was used to assess causality. We also performed a literature search to find publications that report propafenone-associated gross hematuria. FINDINGS: The Naranjo scale generated a score of 6, suggesting a probable association between gross hematuria and propafenone therapy. Thirteen publications that reported an association between gross hematuria and propafenone administration were found. IMPLICATIONS: A probable association exists between gross hematu...
Source: Clinical Therapeutics - June 1, 2019 Category: Drugs & Pharmacology Authors: Chen S, Ding W, Ye J, Wang Z, Zhao X, Cui Y Tags: Clin Ther Source Type: research

Treatment Patterns in Patients With Newly Diagnosed Type 2 Diabetes in China: A Retrospective, Longitudinal Database Study.
The objectives of this study were to examine the patterns of antihyperglycemic drug (AHD) therapy among patients with newly diagnosed type 2 diabetes mellitus (T2DM) in the general Chinese population, stratified by initial hemoglobin (Hb) A1c level, and to assess whether treatment patterns are consistent with the recommendations published in the China Diabetes Society's clinical treatment guideline. METHODS: A retrospective database analysis was conducted, and data were obtained from the SuValue database. Prescribing patterns for diabetes treatments were determined from data obtained from the Nanhai District-based ele...
Source: Clinical Therapeutics - May 30, 2019 Category: Drugs & Pharmacology Authors: Wang C, Gao Y, Zhu L, Huang M, Wu Y, Xuan J Tags: Clin Ther Source Type: research

Real-life Performance of Edoxaban in Elderly Patients With Atrial Fibrillation: a Multicenter Propensity Score-Matched Cohort Study.
Abstract PURPOSE: The purpose of the current study was to compare the efficacy and safety of edoxaban versus vitamin K antagonist (VKA) therapy among a cohort of elderly patients (ie, those aged ≥75 years) with atrial fibrillation (AF) in a real-life setting. METHODS: A propensity score-matched cohort observational study was performed comparing the safety and efficacy of edoxaban versus VKA therapy among a cohort of elderly (aged ≥75 years) patients with AF in a real-life setting. Follow-up data were obtained through outpatient visits at 1, 3, and every 6 months. The primary safety outcome was major ble...
Source: Clinical Therapeutics - May 28, 2019 Category: Drugs & Pharmacology Authors: Russo V, Attena E, Mazzone C, Melillo E, Rago A, Galasso G, Riegler L, Parisi V, Rotunno R, Nigro G, D'Onofrio A Tags: Clin Ther Source Type: research

Real-world Adherence and Persistence with Bisphosphonate Therapy in Postmenopausal Women: A Systematic Review.
The objective of this systematic literature review was to evaluate adherence, persistence, and the impact of adherence and persistence on fracture risk in postmenopausal women with diagnosed osteoporosis. METHODS: Articles eligible for review included observational studies of the real-world use of bisphosphonates in 23 countries and were identified by using MEDLINE, EMBASE, IMSEAR (Index Medicus for South-East Asia Region), and LILACS (Latin American and Caribbean Health Sciences Database). FINDINGS: We identified and evaluated 10 studies that assessed bisphosphonate adherence by measuring medication possession r...
Source: Clinical Therapeutics - May 28, 2019 Category: Drugs & Pharmacology Authors: Fardellone P, Lello S, Cano A, de Sá Moreira E, Watanabe de Oliveira R, Julian GS, Tang B Tags: Clin Ther Source Type: research

Sex and Gender Differences in Cardiovascular Resuscitation, Recovery, and Survival.
PMID: 31133334 [PubMed - as supplied by publisher] (Source: Clinical Therapeutics)
Source: Clinical Therapeutics - May 24, 2019 Category: Drugs & Pharmacology Authors: McGregor AJ Tags: Clin Ther Source Type: research

Can Beliefs Be Modified?
PMID: 31133335 [PubMed - as supplied by publisher] (Source: Clinical Therapeutics)
Source: Clinical Therapeutics - May 24, 2019 Category: Drugs & Pharmacology Authors: Shader RI Tags: Clin Ther Source Type: research

Association of Changes in Anticitrullinated Protein Antibody Levels With Resource Use and Disease Activity Measures in a US Observational Cohort.
Abstract PURPOSE: Anticitrullinated protein antibody (ACPA) concentration, beyond ACPA positivity, is indicative of more aggressive radiographic progression in patients with rheumatoid arthritis (RA). However, there is limited information on the association of changes in ACPA with resource use measures and/or disease activity measures. We evaluate associations between changes in levels of ACPA and outcomes, including durable medical equipment (DME) use, hospitalizations, and disease activity, in patients with established RA. METHODS: Patients from the Brigham and Women's Hospital Rheumatoid Arthritis Sequenti...
Source: Clinical Therapeutics - May 23, 2019 Category: Drugs & Pharmacology Authors: Alemao E, Iannaccone CK, Weinblatt ME, Shadick NA Tags: Clin Ther Source Type: research

Association Between Exposure of Ipratropium and Salmeterol and Diagnosis of Multiple Sclerosis: A Matched Case-control Study.
This study aims at investigating the association between ipratropium and salmeterol and reduced diagnosis of MS with the use of real-world clinical data. METHODS: We conducted a 1:10 matched case-control study that compared the exposure of ipratropium and salmeterol between patients with MS and control patients over the past 2 years, using the MS Flowsheet Registry of OSF HealthCare Saint Francis Medical Center. Cases were matched to control patients, based on service year/quarter, age, sex, race, and payer type. The relationship was examined with a Poisson regression model and a generalized structural equation model....
Source: Clinical Therapeutics - May 22, 2019 Category: Drugs & Pharmacology Authors: Ren J, Ascencio M, Raimondi T, Rainville EC, Valenzuela RM, Asche CV Tags: Clin Ther Source Type: research

Influence of CYP450 Enzymes, CES1, PON1, ABCB1, and P2RY12 Polymorphisms on Clopidogrel Response in Patients Subjected to a Percutaneous Neurointervention.
D, Abad-Santos F Abstract PURPOSE: Clopidogrel is a thienopyridine prodrug that inhibits platelet aggregation. It is prescribed to prevent atherothrombotic and thromboembolic events in patients receiving a stent implant in carotid, vertebral, or cranial arteries. The influence of cytochrome P-450 (CYP) 2C19 on the response to clopidogrel has been widely studied; however, the effect of other genes involved in clopidogrel absorption and metabolism has not been established in this cohort of patients. METHODS: This observational retrospective study assessed the antiplatelet response and the prevalence of hemorrh...
Source: Clinical Therapeutics - May 22, 2019 Category: Drugs & Pharmacology Authors: Saiz-Rodríguez M, Belmonte C, Caniego JL, Koller D, Zubiaur P, Bárcena E, Romero-Palacián D, Eugene AR, Ochoa D, Abad-Santos F Tags: Clin Ther Source Type: research

Tolerability and Pharmacokinetics of Contezolid at Therapeutic and Supratherapeutic Doses in Healthy Chinese Subjects, and Assessment of Contezolid Dosing Regimens Based on Pharmacokinetic/Pharmacodynamic Analysis.
This study assessed the tolerability and pharmacokinetic (PK) properties of a new-generation oxazolidinone, contezolid (MRX-I), and its major inactive metabolite, M2, after single oral administrations of 800, 1200, and 1600 mg in the fed state, and compared the efficacy of 3 dosing regimens in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection based on PK/pharmacodynamic (PD) analysis. METHODS: A Phase I study at a single study center was conducted with 2 parts. In the first part, 20 healthy subjects received a single oral dose of 1200 or 1600 mg of contezolid or placebo in the fed...
Source: Clinical Therapeutics - May 21, 2019 Category: Drugs & Pharmacology Authors: Wu J, Wu H, Wang Y, Chen Y, Guo B, Cao G, Wu X, Yu J, Wu J, Zhu D, Guo Y, Yuan H, Hu F, Zhang J Tags: Clin Ther Source Type: research