A Systematic Review: Single-pill Combination Therapy of Azilsartan Medoxomil/Chlorthalidone-one of Novel Choice in the Treatment of Hypertension.
Abstract PURPOSE: The goal of this study was to review recent clinical studies of azilsartan medoxomil (AZL-M) and chlorthalidone (CLD), a combined angiotensin receptor blocker and thiazide-like diuretic, and its role in recently published guidelines. This review explores the role of AZL-M/CLD in treating patients with hypertension. METHODS: A systematic review of literature published from 1990 to 2018 was performed by using the following key words: Edarbyclor, azilsartan, chlorthalidone, pharmacokinetic, and hypertension. Available English-language data from reviews, abstracts, presentations, and clinical tr...
Source: Clinical Therapeutics - June 25, 2020 Category: Drugs & Pharmacology Authors: Kwon A, Kim GH Tags: Clin Ther Source Type: research

Effectiveness and Adverse Events of Use of Natalizumab in a Brazilian Cohort of Patients With Multiple Sclerosis.
This study evaluated the effectiveness and adverse events of NTZ in a cohort of Brazilian patients with MS, as well as the impact of clinical and demographic factors on patient response to treatment. METHODS: This multicenter, Brazilian observational study was conducted from January 2011 until December 2016 and included patients with RRMS (McDonald criteria 2005 and 2010) aged ≥18 years treated with NTZ for at least 3 months. Demographic, clinical, and radiologic data were obtained from medical records and during follow-up visits. The primary outcomes investigated were the absolute number of relapses and annualized...
Source: Clinical Therapeutics - June 24, 2020 Category: Drugs & Pharmacology Authors: Deslandes MQ, Alves PT, Alvarenga MP, Lessa VCC, Camargo S, Alvarenga RMP, Vasconcelos CC Tags: Clin Ther Source Type: research

Medical Foods-A Closer Look at the Menu: A Brief Review and Commentary.
Abstract The notion of a medical food-a foodstuff that, by definition, must be obtained and used while under medical supervision, and regulated by the US Food and Drug Administration, is a source of considerable confusion to the lay public as well as many-if not most-in the health professions community. Such restrictions are more often associated with pharmaceutical agents or medical devices. Additionally, specific regulatory aspects of medical foods are overseen by the US Food and Drug Administration, and these specifics appear to overlap with other foods and dietary supplements in terms of requirements and allow...
Source: Clinical Therapeutics - June 24, 2020 Category: Drugs & Pharmacology Authors: Markowitz JS, Gurley PC, Gurley BJ Tags: Clin Ther Source Type: research

Cost-Effectiveness and Net Monetary Benefit of olaparib Maintenance Therapy Versus No Maintenance Therapy After First-Line Platinum-Based Chemotherapy in Newly Diagnosed Advanced BRCA1/2-Mutated Ovarian Cancer in the Italian National Health Service.
Abstract PURPOSE: The aim of this study was to evaluate the cost-effectiveness and net monetary benefit of olaparib maintenance therapy compared with no maintenance therapy after first-line platinum-based chemotherapy in newly diagnosed advanced BRCA1/2-mutated ovarian cancer from the Italian National Health Service (NHS) perspective. METHODS: We developed a lifetime Markov model in which a cohort of patients with newly diagnosed advanced BRCA1/2-mutated ovarian cancer was assigned to receive either olaparib maintenance therapy or active surveillance (Italian standard of care) after first-line platinum-based ...
Source: Clinical Therapeutics - June 23, 2020 Category: Drugs & Pharmacology Authors: Patrizio A, Ludovica B, Giulia F, Claudio J, Nicoletta C, Francesco C Tags: Clin Ther Source Type: research

Population Pharmacokinetics Analysis of Quetiapine Extended-release Formulation in Japanese Patients with Bipolar Depression.
The objectives of this study were to explore covariates of plasma quetiapine concentrations after oral administration of quetiapine extended-release formulation (XR), and to examine the exposure-response relationship in Japanese patients with bipolar depression, using population pharmacokinetics (PopPK) modeling. METHODS: In a multicenter, randomized, double-blind, placebo-controlled study of quetiapine XR in patients with bipolar depression, plasma for the measurement of quetiapine concentration was collected at weeks 2, 4, 8, 12, 20, 28, and 52 during oral administration of 150 or 300 mg once daily of quetiapin...
Source: Clinical Therapeutics - June 6, 2020 Category: Drugs & Pharmacology Authors: Fukushi R, Nomura Y, Katashima M, Komatsu K, Sato Y, Takada A Tags: Clin Ther Source Type: research

Effects of Injected Antiosteoporotic Medication Versus Oral Bisphosphonates on Rates of Repeated Vertebroplasty or Kyphoplasty.
Abstract PURPOSE: Vertebral compression fractures can recur within a few years after percutaneous vertebroplasty (PVP) or kyphoplasty. METHODS: We conducted a population-based study using data from the Taiwan National Health Insurance Research Database to investigate the efficacy of various antiosteoporotic treatments in reducing the prevalence rate of repeated PVP or kyphoplasty in patients hospitalized from January 1, 1997, to December 31, 2004. We included patients with vertebral compression fractures after PVP or kyphoplasty who received oral bisphosphonates (OB group; n = 6141) or injected drug...
Source: Clinical Therapeutics - June 5, 2020 Category: Drugs & Pharmacology Authors: Kao FC, Hsu YC, Chen TS, Tu YK, Liu PH Tags: Clin Ther Source Type: research

Effect of Abaloparatide on Bone Mineral Density and Fracture Incidence in a Subset of Younger Postmenopausal Women with Osteoporosis at High Risk for Fracture.
Abstract PURPOSE: Current treatment guidelines recommend treatment for postmenopausal women with a T score
Source: Clinical Therapeutics - June 5, 2020 Category: Drugs & Pharmacology Authors: Saag KG, Williams SA, Wang Y, Weiss RJ, Cauley JA Tags: Clin Ther Source Type: research

Misdosing of Non-Vitamin K Antagonist Oral Anticoagulants in Primary Care.
R, Miguel S, Queirós T, Santo G, Silva F, Sargento-Freitas J Abstract PURPOSE: Prescription patterns of non-vitamin K antagonist oral anticoagulants (NOACs) are unknown among primary care physicians, where most patients with nonvalvular atrial fibrillation (NVAF) are diagnosed and followed up. The goal of this study was to evaluate overdosing and underdosing of NOACs in patients with NVAF followed up in primary care and determine their clinical predictors. METHODS: This multicenter cross-sectional study included all patients with NVAF followed up in 13 primary care units in the center region of Portuga...
Source: Clinical Therapeutics - June 5, 2020 Category: Drugs & Pharmacology Authors: Cardoso CS, Sousa JA, Simões P, Silva B, Albuquerque A, Esperança A, Cibrão A, Correia A, Gonçalves J, Mortágua J, Almeida JE, Oliveira L, Garcia J, Duarte M, Loureiro M, Costa E Silva M, Fraga M, Lopes P, Brandão R, Miguel S, Queirós T, Santo G, S Tags: Clin Ther Source Type: research

Stress and altered immune function: Programming throughout the lifespan.
PMID: 32505494 [PubMed - as supplied by publisher] (Source: Clinical Therapeutics)
Source: Clinical Therapeutics - June 4, 2020 Category: Drugs & Pharmacology Authors: Maron JL Tags: Clin Ther Source Type: research

Narrative Summary of Recently Published Literature on Intravenous Ibuprofen.
Abstract PURPOSE: This is a narrative review of the published literature on IV ibuprofen (IVIB) as one of the drugs used in multimodal pain management in inpatients and outpatients pre- and postoperatively and for nonsurgical pain or fever. METHODS: The efficacy, concurrent opioid use, pharmacokinetic properties, tolerability, stress response, and postoperative recovery with IVIB, which were investigated in 9 clinical studies, are presented in this narrative review. In total, 344 adult patients and healthy volunteers were included in these 9 studies; 200 of these subjects received IVIB, and the remaining...
Source: Clinical Therapeutics - June 3, 2020 Category: Drugs & Pharmacology Authors: Southworth SR, Sellers JA Tags: Clin Ther Source Type: research

Signal Management in Pharmacovigilance: A Review of Activities and Case Studies.
Abstract PURPOSE: After nearly 12 decades of pharmaceutical catastrophes and the associated groundbreaking regulatory innovations, pharmacovigilance has come down to us in the present day as 3 interlocking core disciplines: case management, signal management, and benefit-risk management. This review provides a state-of-the-art introduction to the great variety of sources of safety information, both dependent on and independent of the Individual Case Safety Report (ICSR), and explains how this content undergoes management-system processes with globally accepted definitions, standards, and structures that make possi...
Source: Clinical Therapeutics - May 30, 2020 Category: Drugs & Pharmacology Authors: Beninger P Tags: Clin Ther Source Type: research

Are Recently Evaluated Drugs More Likely to Receive Positive Reimbursement Recommendations in South Korea? 11-Year Experience of the South Korean Positive List System.
This study sought to examine whether positive reimbursement recommendations of pharmaceuticals have increased since 2014. METHODS: Industry submissions evaluated from January 2007 to December 2018 were identified, and characteristics relevant to reimbursement recommendations were extracted. Logistic regression analyses with robust SEs were used to quantify the likelihood of positive recommendations for pharmaceuticals, after controlling for relevant factors influencing the recommendations. FINDINGS: During the study period, 355 (72.9%) of 487 submissions were positively recommended; the drugs evaluated after 2014...
Source: Clinical Therapeutics - May 30, 2020 Category: Drugs & Pharmacology Authors: Gong JR, Lee D, Lim KM, Bae S Tags: Clin Ther Source Type: research

Pharmacokinetics of Inhaled Levodopa Administered With Oral Carbidopa in the Fed State in Patients With Parkinson's Disease.
Abstract PURPOSE: Levodopa (LD) is the most effective oral pharmacotherapy for the management of motor symptoms in Parkinson's disease. However, LD use is complicated by a progressive shortening of the duration of efficacy of a dose, resulting in episodes of inadequate responsiveness, or OFF periods. OFF periods may also occur unpredictably, partly due to the pharmacokinetic (PK) variability of oral LD, resulting from gastrointestinal dysfunction and from the effects of food on absorption. CVT-301 is a levodopa inhalation powder for the treatment of OFF period symptoms in patients on oral dopa-decarboxylase i...
Source: Clinical Therapeutics - May 29, 2020 Category: Drugs & Pharmacology Authors: Safirstein BE, Ellenbogen A, Zhao P, Henney HR, Kegler-Ebo DM, Oh C Tags: Clin Ther Source Type: research

Elevated Circulating Th2 Cells in Women With Asthma and Psychological Morbidity: A New Asthma Endotype?
Abstract PURPOSE: Psychological stress shifts the immune system toward the production of T-helper (Th)-2-mediated cytokines and eosinophilia, increases the risks for both asthma and depression, and can precipitate asthma exacerbations. Th2-mediated inflammation is a characteristic of allergic asthma. We have shown that the levels of CD4+ Th2 cells in the peripheral blood of patients with asthma are associated with severity and/or control of the disease. To improve our understanding of the interactions between stress and asthma symptoms, we evaluated the effects of psychological comorbidity on Th2-mediated inf...
Source: Clinical Therapeutics - May 29, 2020 Category: Drugs & Pharmacology Authors: Cameron L, Palikhe NS, Laratta C, Vliagoftis H Tags: Clin Ther Source Type: research

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ASP3652, a Reversible Fatty Acid Amide Hydrolase Inhibitor, in Healthy, Nonelderly, Japanese Men and Elderly, Japanese Men and Women: A Randomized, Double-blind, Placebo-controlled, Single and Multiple Oral Dose, Phase I Study.
This study aimed to evaluate the safety, tolerability, and pharmacokinetic and pharmacodynamic properties of ASP3652, a peripherally acting inhibitor of peripheral fatty acid amide hydrolase (FAAH) after 30-, 100-, 300-, 600-, and 900-mg single and 100- and 300-mg BID multiple oral dose in Japanese patients. METHODS: This was a randomized, double-blind, placebo-controlled, single and multiple oral dose Phase I study in healthy, nonelderly men and elderly men and women. The study consisted of 2 parts: in the single oral dose part, 40 healthy, nonelderly men were randomized to receive placebo or ASP3652; in the multiple...
Source: Clinical Therapeutics - May 23, 2020 Category: Drugs & Pharmacology Authors: Takizawa M, Hatta T, Iitsuka H, Katashima M, Sato Y, Kuroishi K, Nagashima H Tags: Clin Ther Source Type: research

Dosage Optimization of Efavirenz Based on a Population Pharmacokinetic-Pharmacogenetic Model of HIV-infected Patients in Thailand.
This study aimed to develop a population model of the pharmacokinetic properties of efavirenz, and to investigate the impact of patients' characteristics and CYP2B6 516G > T polymorphism on the pharmacokinetic properties of efavirenz. Model-based simulations were performed to provide genotype-based dosage optimization in a Thai population. METHODS: Plasma efavirenz concentrations measured at 12 h post-dose in 360 Thai HIV-infected patients with and without tuberculosis were analyzed by the nonlinear mixed-effects modeling approach. A 1-compartment model with first-order absorption and elimination was...
Source: Clinical Therapeutics - May 22, 2020 Category: Drugs & Pharmacology Authors: Chaivichacharn P, Avihingsanon A, Manosuthi W, Ubolyam S, Tongkobpetch S, Shotelersuk V, Punyawudho B Tags: Clin Ther Source Type: research

Effect of Stress on Neuroimmune Processes.
Abstract PURPOSE: Psychological stress worsens many diseases, especially those with inflammatory components, such as atopic dermatitis (AD) and autism spectrum disorder (ASD), conditions that are significantly correlated in large epidemiologic studies. However, how stress contributes to these conditions is still poorly understood. This narrative review of the relevant literature advances the premise that stress affects inflammatory processes in AD and ASD via stimulation of mast cells (MCs). METHODS: MEDLINE was searched between 1980 and 2019 using the terms allergies, atopic dermatitis, autism spectrum disor...
Source: Clinical Therapeutics - May 22, 2020 Category: Drugs & Pharmacology Authors: Theoharides TC Tags: Clin Ther Source Type: research

Reviewing the Evidence on Vitamin D Supplementation in the Management of Testosterone Status and Its Effects on Male Reproductive System (Testis and Prostate): Mechanistically Dazzling but Clinically Disappointing.
Abstract PURPOSE: Vitamin D supplementation has been suggested to increase testosterone levels. The primary purpose of this literature review was to critically assess the physiologic effects of vitamin D supplementation on serum testosterone concentrations in men and the secondary purpose was to evaluate the feasibility of vitamin D status toward urologic health (testis and prostate). METHODS: A structured literature review was performed using the Cochrane, MEDLINE, and Web of Science databases. The literature search encompassed studies published between 2011 and 2019. FINDINGS: Observational studies sug...
Source: Clinical Therapeutics - May 20, 2020 Category: Drugs & Pharmacology Authors: Santos HO, Howell S, Nichols K, Teixeira FJ Tags: Clin Ther Source Type: research

Communication of Medication Nonmedical Switching Policies and Procedures by Insurance Companies: Results of an E-Survey.
Abstract PURPOSE: Nonmedical switching is defined as a change in a stable patient's prescribed medication to a clinically distinct, nongeneric alternative for reasons other than lack of clinical response, adverse effects, or poor adherence. Nonmedical switching often results from formulary changes implemented by insurers to lower medication costs. We sought to survey randomly sampled physicians to elicit their opinions regarding insurers' communication about nonmedical switching. METHODS: We performed an online, cross-sectional survey of licensed, practicing physicians who were>2 years but
Source: Clinical Therapeutics - May 14, 2020 Category: Drugs & Pharmacology Authors: Salam T, Duhig A, Patel AA, Cameron A, Voelker J, Bookhart B, Coleman CI Tags: Clin Ther Source Type: research

Population Pharmacokinetics Study of Contezolid (MRX-I), a Novel Oxazolidinone Antibacterial Agent, in Chinese Patients.
Abstract PURPOSE: Contezolid (MRX-I) is a novel oxazolidinone with potent in vitro activity against gram-positive pathogens. The aim of this study was to establish the dose-pharmacokinetic (PK) exposure-pharmacodynamic (PD)-response relationship and to quantitatively evaluate the variability of MRX-I after continuous oral administration of 600 mg BID and 800 mg BID for 14 days under fed conditions in patients with skin and skin structure infections. Another goal was to evaluate the 2 dosing regimens against methicillin-resistant Staphylococcus aureus infections based on PK/PD analysis. METHODS:...
Source: Clinical Therapeutics - May 7, 2020 Category: Drugs & Pharmacology Authors: Li L, Wu H, Chen Y, Yuan H, Wu J, Wu X, Zhang Y, Cao G, Guo B, Wu J, Zhao M, Zhang J Tags: Clin Ther Source Type: research

Effectiveness of Fimasartan and Rosuvastatin Combination Treatment in Hypertensive Patients With Dyslipidemia.
Abstract PURPOSE: The goal of this study was to evaluate the concurrent control rate of hypertension and dyslipidemia by fimasartan and rosuvastatin in patients who were concomitantly prescribed both drugs. METHODS: This single-center, cross-sectional study was conducted in 536 patients with hypertension and dyslipidemia who were taking fimasartan and rosuvastatin together for at least 12 weeks. Patients were enrolled from October 2016 to March 2018 at a tertiary hospital in the Republic of Korea. The primary end point was the concurrent control rate of blood pressure (
Source: Clinical Therapeutics - May 3, 2020 Category: Drugs & Pharmacology Authors: Lee SJ, Oh J, Hong SJ, Cho IJ, Kim SR, Uhm JS, Shim CY, Chang HJ, Ahn CM, Kim JS, Kim BK, Park S, Lee SH, Hong GR, Ko YG, Choi D Tags: Clin Ther Source Type: research

Consider Clinical Therapeutics for Your Next Psychiatry Submission.
PMID: 32371088 [PubMed - as supplied by publisher] (Source: Clinical Therapeutics)
Source: Clinical Therapeutics - May 1, 2020 Category: Drugs & Pharmacology Authors: Citrome L Tags: Clin Ther Source Type: research

An Assessment of Pharmacokinetic Interaction between Lobeglitazone and Sitagliptin after Multiple Oral Administrations in Healthy Men.
The objective of this study was to investigate a possible pharmacokinetic interaction between lobeglitazone and sitagliptin after multiple oral administrations in healthy Korean men. METHODS: Two randomized, open-label, multiple-dose, 2-way crossover studies were conducted simultaneously in healthy men. In study 1, men were randomly assigned to 1 of 2 sequences, and 1 of the following treatments was administered in each period: 1 tablet of lobeglitazone sulfate (0.5 mg) once daily for 5 days and or 1 tablet each of lobeglitazone sulfate (0.5 mg) and sitagliptin (100 mg) once daily for 5 days. In study 2...
Source: Clinical Therapeutics - April 30, 2020 Category: Drugs & Pharmacology Authors: Moon SJ, Yu KS, Kim MG Tags: Clin Ther Source Type: research

Possible Influence of the Route of Treatment Administration on Treatment Adherence in Patients With Multiple Sclerosis.
Guarnizo E, Meca Lallana JE, Zafrilla Rentero P Abstract PURPOSE: Multiple sclerosis is a chronic, demyelinating, and degenerative disease of the central nervous system with an immune-based pathologic origin. The present pilot study aimed to assess whether the change in the route of treatment administration is associated with a variation in adherence and whether there is a change in quality of life, treatment satisfaction, and fatigue. METHODS: Patients with relapsing-remitting multiple sclerosis who were>18 years of age and who used to receive immunomodulatory parenteral treatment and were ready to change...
Source: Clinical Therapeutics - April 30, 2020 Category: Drugs & Pharmacology Authors: Sánchez Martínez I, Cerdán Sánchez M, López Román J, Iniesta Martínez F, Carreón-Guarnizo E, Meca Lallana JE, Zafrilla Rentero P Tags: Clin Ther Source Type: research

Psychological stress and chronic urticaria: A neuro-immuno-cutaneous crosstalk. A systematic review of the existing evidence.
Abstract PURPOSE: It has been observed that certain patients with chronic spontaneous or idiopathic urticaria (CSU/CIU) have a personal history of a significant stressor before urticaria onset, while the prevalence of any psychopathology among these patients is significantly higher than in healthy individuals. Research has confirmed that skin is both an immediate stress perceiver and a target of stress responses. These complex interactions between stress, skin, and the nervous system may contribute to the onset of chronic urticaria. This systematic review investigated the association between CSU/CIU and neuroimmun...
Source: Clinical Therapeutics - April 29, 2020 Category: Drugs & Pharmacology Authors: Konstantinou GN, Konstantinou GN Tags: Clin Ther Source Type: research

Cost-effectiveness and Net Monetary Benefit of durvalumab Consolidation Therapy Versus No Consolidation Therapy After Chemoradiotherapy in Stage III Non-small Cell Lung Cancer in the Italian National Health Service.
Abstract PURPOSE: The aim of this study was to evaluate the cost-effectiveness and net monetary benefit of durvalumab consolidation therapy compared with no consolidation therapy after chemoradiotherapy in patients with stage III non-small cell lung cancer with programmed cell death 1 ligand 1 expression ≥1% from the Italian National Health Service perspective. METHODS: We developed a 12-month decision tree combined with a lifetime cohort Markov model in which patients were assigned to receive durvalumab consolidation therapy or active follow-up (Italian standard of care) after chemoradiotherapy to compare...
Source: Clinical Therapeutics - April 27, 2020 Category: Drugs & Pharmacology Authors: Patrizio A, Ludovica B, Giulia F, Claudio J, Francesco G, Francesco C Tags: Clin Ther Source Type: research

Midazolam intoxication in a premature neonate.
We report the case of a male neonate with a respiratory disorder who developed adverse cardiorespiratory symptoms after the continuous infusion of midazolam. METHODS: To clarify the cause of cardiogenic shock, we performed whole exome sequencing and screened relative single-nucleotide variants of 2 cytochrome P450 (CYP) isoforms, CYP3A4 and CYP3A5, which play a dominant role in the metabolic elimination of midazolam. We measured endogenous cortisol 6β-hydroxylation clearance to phenotypically assess CYP3A activity. FINDINGS: The CYP3A activity level in the patient was significantly lower than the mean CYP3A ...
Source: Clinical Therapeutics - April 27, 2020 Category: Drugs & Pharmacology Authors: Endo M, Hirano R, Shibasaki H, Yokokawa A, Furuta T, Abe K, Morita K, Tanaka S, Hirano T, Sakurai M, Mizuno K Tags: Clin Ther Source Type: research

Cost-effectiveness Comparison of Ceftazidime/Avibactam Versus Meropenem in the Empirical Treatment of Hospital-acquired Pneumonia, Including Ventilator-associated Pneumonia, in Italy.
The objective of this analysis was to compare the cost-effectiveness of CAZ-AVI versus meropenem in the empirical treatment of appropriate hospitalized patients with HAP/VAP caused by gram-negative pathogens, from the perspective of publicly funded health care in Italy (third-party perspective, based on the data from the REPROVE (Ceftazidime-Avibactam Versus Meropenem In Nosocomial Pneumonia, Including Ventilator-Associated Pneumonia) clinical study; ClinicalTrials.gov NCT01808092). METHODS: A patient-level, sequential simulation model of the HAP/VAP clinical course was developed using spreadsheet software. The analys...
Source: Clinical Therapeutics - April 26, 2020 Category: Drugs & Pharmacology Authors: Tichy E, Torres A, Bassetti M, Kongnakorn T, Di Virgilio R, Irani P, Charbonneau C Tags: Clin Ther Source Type: research

Use of real-world data for new drug applications and line extensions.
TC Abstract PURPOSE: For this article, the authors compiled, summarized, and analyzed data from 27 cases in which real-world data (RWD) were applied in regulatory approval. The aims were to provide an overview of RWD, based on classifications per therapeutic area, age group, drivers of acceptability, utility, data sources, and timelines, and to present insights on how it has been applied in regulatory decision making to date. METHODS: Clarivate Analytics was commissioned to collect data from cases in which RWD was used for new drug applications and line extensions submitted to the European Medicines Agency (...
Source: Clinical Therapeutics - April 24, 2020 Category: Drugs & Pharmacology Authors: Bolislis WR, Fay M, Kühler TC Tags: Clin Ther Source Type: research

Determination of Psychological Stress, Serum Immune Parameters, and Cortisol Levels in Patients With Human Papilloma Virus.
This study is among the first to investigate the correlation between psychological, neurohormonal, and immune indicators of stress. PMID: 32340917 [PubMed - as supplied by publisher] (Source: Clinical Therapeutics)
Source: Clinical Therapeutics - April 24, 2020 Category: Drugs & Pharmacology Authors: Cvitanović H, Milošević M, Bukvić-Bešlić I, Lugović-Mihić L Tags: Clin Ther Source Type: research

Hypoglycemia Induced by Hydroxychloroquine Sulfate in a Patient Treated for Connective Tissue Disease Without Diabetes Mellitus.
This study describes a nondiabetic patient who experienced serious hypoglycemia related to HCQ. FINDINGS: In the course of treatment, the patient experienced multiple episodes of hypoglycemia at night and in the early morning. The hypoglycemia was usually accompanied by nausea, fatigue, and dizziness. The lowest value of blood glucose in the fingertip was 2.6 mmol/L. IMPLICATIONS: This rare case will prompt clinicians to pay attention to unexplained hypoglycemia when using HCQ in nondiabetic patients. (Clin Ther. 2020;42:XXX-XXX) © 2020 Elsevier HS Journals, Inc. PMID: 32336573 [PubMed - as supplie...
Source: Clinical Therapeutics - April 23, 2020 Category: Drugs & Pharmacology Authors: Dai Y, Lin G, Shi D Tags: Clin Ther Source Type: research

Efficacy and safety of proposed bevacizumab biosimilar BE1040V in patients with metastatic colorectal cancer: A phase III, randomized, double-blind, noninferiority clinical trial.
S Abstract PURPOSE: The purpose of this study was to compare the efficacy and safety of a proposed bevacizumab biosimilar to those of the reference product in patients with metastatic colorectal cancer (mCRC). METHODS: This Phase III, multicenter, randomized, double-blind (patient- and assessor-blind), active-controlled, 2-armed, parallel-group, noninferiority trial was conducted in patients with histologically verified colorectal cancer with evidence of at least 1 metastasis. Patients with mCRC were randomized 2:1 to receive 5 mg/kg IV of either study drug plus FOLFIRI-3 (with repeated irinotecan 100&nb...
Source: Clinical Therapeutics - April 22, 2020 Category: Drugs & Pharmacology Authors: Rezvani H, Mortazavizadeh SM, Allahyari A, Nekuee A, Najafi SN, Vahidfar M, Ghadyani M, Khosravi A, Qarib S, Sadeghi A, Esfandbod M, Rajaeinejad M, Rezvani A, Hajiqolami A, Payandeh M, Shazad B, Anjidani N, Meskinimood S, Alikhasi A, Karbalaeian M, Salari Tags: Clin Ther Source Type: research

The Skin-Immune System Interface.
PMID: 32321649 [PubMed - as supplied by publisher] (Source: Clinical Therapeutics)
Source: Clinical Therapeutics - April 19, 2020 Category: Drugs & Pharmacology Authors: Jhaveri R Tags: Clin Ther Source Type: research

Reprogramming of the Immune System by Stress and Faulty Hormonal Imprinting.
Abstract PURPOSE: Hormonal imprinting is taking place perinatally at the first encounter between the developing hormone receptors and their target hormones. However, in this crucial period when the developmental window for physiological imprinting is open, other molecules, such as synthetic hormones and endocrine disruptors can bind to the receptors, leading to faulty imprinting with life-long consequences, especially to the immune system. This review presents the factors of stress and faulty hormonal imprinting that lead to reprogramming of the immune system. METHODS: Relevant publications from Pubmed since ...
Source: Clinical Therapeutics - April 16, 2020 Category: Drugs & Pharmacology Authors: Csaba G Tags: Clin Ther Source Type: research

Use of Direct Oral Anticoagulants Versus Traditional Therapies for Acute Venous Thromboembolism After Direct Discharge From the Emergency Department or After Hospitalization: An Audit of 16 Canadian Hospitals.
This study compares and describes the use of direct oral anticoagulants (DOACs) versus traditional therapies (parenteral anticoagulant with or without warfarin) for acute venous thromboembolism (VTE) between individuals discharged directly from the emergency department (ED) versus those hospitalized. This study also reports patterns based on discharge from an academic, community, or rural-based site. METHODS: This retrospective medical records study included patients discharged with acute VTE (2015-2016) from 16 institutions across 4 provinces. Patients with atypical clots, other indications for anticoagulants, or an anticipated lifespan
Source: Clinical Therapeutics - April 10, 2020 Category: Drugs & Pharmacology Authors: Bungard TJ, Ritchie B, Bolt J, Thomson P, Semchuk WM Tags: Clin Ther Source Type: research

Optimizing Medication Use in Older Adults.
PMID: 32284190 [PubMed - as supplied by publisher] (Source: Clinical Therapeutics)
Source: Clinical Therapeutics - April 10, 2020 Category: Drugs & Pharmacology Authors: Hung WW, Chow S Tags: Clin Ther Source Type: research

Stress-Induced Interaction of Skin Immune Cells, Hormones, and Neurotransmitters.
Abstract PURPOSE: Although scientific articles mention the impact of psychological stress on skin diseases, few review the latest research on factors involved in this correlation. The skin actively responds to psychological stress, with involvement of skin immune cells, hormones, neurotransmitters. Skin immune cells actively regulate tissue inflammation with their proinflammatory and anti-inflammatory effects. Stress-induced skin reactions primarily include cytokine secretion (e.g. interleukin-6, interleukin-1, interferon-γ) and activation of skins peripheral corticotropin-releasing hormone (CRH)-proopiomela...
Source: Clinical Therapeutics - April 7, 2020 Category: Drugs & Pharmacology Authors: Pondeljak N, Lugović-Mihić L Tags: Clin Ther Source Type: research

Valproic Acid for the Management of Agitation and Delirium in the Intensive Care Setting: A Retrospective Analysis.
The objective of this analysis was to assess the efficacy and safety associated with the use of valproic acid for the management of agitation and delirium in the ICU. METHODS: This retrospective descriptive analysis included patients who were prescribed valproic acid for a minimum of 3 days for the treatment of agitation and/or delirium in the cardiac, surgical, or medical ICU from May 31, 2015 to December 31, 2017. The prevalence of agitation and delirium was assessed during valproic acid therapy for up to 7 days. Additional data analyzed included opioid, sedative, and antipsychotic requirements and safety outcomes. ...
Source: Clinical Therapeutics - April 6, 2020 Category: Drugs & Pharmacology Authors: Crowley KE, Urben L, Hacobian G, Geiger KL Tags: Clin Ther Source Type: research

Comparison of the Ultrathin Strut, Biodegradable Polymer Sirolimus-eluting Stent With a Durable Polymer Everolimus-eluting Stent in a Chinese Population: The Randomized BIOFLOW VI Trial.
Abstract PURPOSE: The BIOFLOW-VI (Biotronik-Safety and Clinical Performance of the Drug Eluting Orsiro Stent in the Treatment of Subjects With De Novo Coronary Artery Lesions-VI) study evaluates the angiographic efficacy, clinical safety, and effectiveness of the ultrathin strut, biodegradable polymer sirolimus-eluting stent (BP-SES) compared with a durable polymer everolimus-eluting stent (DP-EES). This randomized controlled clinical trial was designed to enable approval of new drug-eluting stents in China. METHODS: A total of 440 eligible patients from 11 sites with up to 2 de novo native coronary artery le...
Source: Clinical Therapeutics - April 5, 2020 Category: Drugs & Pharmacology Authors: Li C, Yang Y, Han Y, Song D, Xu J, Guan C, Gao R, Garcia-Garcia HM, Waksman R, Xu B, BIOFLOW VI Trial Investigators Tags: Clin Ther Source Type: research

Patient Safety.
PMID: 32265060 [PubMed - as supplied by publisher] (Source: Clinical Therapeutics)
Source: Clinical Therapeutics - April 5, 2020 Category: Drugs & Pharmacology Authors: Jhaveri R Tags: Clin Ther Source Type: research

A Phase I Study on the Pharmacokinetics and Pharmacodynamics of DJT1116PG, a Novel Selective Inhibitor of Sodium-Glucose Cotransporter Type 2, in Healthy Individuals at Steady State.
Abstract PURPOSE: DJT1116PG, which selectively inhibits renal glucose reabsorption by inhibiting sodium-glucose cotransporter type 2, was developed as an insulin-independent treatment for type 2 diabetes mellitus. This Phase I trial evaluated the pharmacokinetic and pharmacodynamic properties of DJT1116PG at steady state in healthy Chinese individuals. METHODS: This was a multiple ascending dose study of DJT1116PG (20, 50, and 100 mg once daily for 7 days) that included 36 healthy individuals. FINDINGS: There were no serious adverse events or deaths in these studies, and no adverse event led to stud...
Source: Clinical Therapeutics - April 4, 2020 Category: Drugs & Pharmacology Authors: Zhang H, Liu J, Zhu X, Li X, Chen H, Wu M, Li C, Ding Y Tags: Clin Ther Source Type: research

Relative Bioavailability of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Administered With and Without a Spacer: Results of a Phase I, Randomized, Crossover Trial in Healthy Adults.
Abstract PURPOSE: The triple combination therapy budesonide/glycopyrrolate/formoterol fumarate in a metered dose inhaler (BGF MDI), formulated by using innovative co-suspension delivery technology, is a new inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2-agonist fixed-dose combination for the maintenance treatment of COPD. For some patients, the use of an MDI may be optimized with a spacer. This Phase I study assessed the effect of a spacer on lung exposure, total systemic exposure, and safety of BGF MDI 320/36/9.6 μg in healthy subjects. METHODS: This randomized, ope...
Source: Clinical Therapeutics - April 3, 2020 Category: Drugs & Pharmacology Authors: Dorinsky P, DePetrillo P, DeAngelis K, Trivedi R, Darken P, Gillen M Tags: Clin Ther Source Type: research

Adverse Outcomes Associated with Inpatient Administration of Beers List Medications Following Total Knee Replacement.
Abstract PURPOSE: Beers List drugs are potentially harmful in older adults and are grouped by level of risk. Over 9000 total knee arthroplasties (TKAs) are performed each year Veterans Affairs (VA) hospitals, primarily on older adults. Minimal data on the administration of Beers List drugs following arthroplasty currently exists in the literature. Our goal was to quantify the risks of these drugs following TKA. We hypothesized that increasing doses of Beers List drugs would be associated with increased risks for readmission, reoperation, emergency department (ED) visits, and mortality. METHODS: In this r...
Source: Clinical Therapeutics - April 3, 2020 Category: Drugs & Pharmacology Authors: Anderson BJ, Liu M, Cui X, Stevens M, Arensman MA Tags: Clin Ther Source Type: research

Effect of Ketamine Added to Ropivacaine in Nerve Block for Postoperative Pain Management in Patients Undergoing Anterior Cruciate Ligament Reconstruction: a Randomized Trial.
Abstract PURPOSE: Nerve blocks are commonly used as a part of multimodal pain relief. It was previously shown that ketamine could enhance the analgesic effect of local anesthetics in nerve blocks. A literature review on adding ketamine to local anesthetics for ameliorating analgesia revealed inconsistencies in analgesic efficiency and safety. This prospective, randomized, double-blind trial was performed to evaluate the antinociceptive effect of mixing ketamine with local anesthetics in a combined femoral and sciatic nerve block (CFSNB) during anterior cruciate ligament (ACL) reconstruction. METHODS: Seventy-...
Source: Clinical Therapeutics - April 1, 2020 Category: Drugs & Pharmacology Authors: Zhu T, Gao Y, Xu X, Fu S, Lin W, Sun J Tags: Clin Ther Source Type: research

Comparing Outcomes between Thiazide Diuretics and Other First-Line Antihypertensive Drugs in Long-term Nursing Home Residents.
The objectives of this study were to describe the patterns of antihypertensive medication treatment in this population, focusing on thiazide diuretics, and to determine the association between thiazide diuretics (DIURs) and outcomes important to NH patients. METHODS: This observational cohort study was conducted in long-term NH residents treated for hypertension in the second quarter (Q2) of 2013, from all US NHs. The primary exposure was the frequency of use of antihypertensive treatment class (DIURs, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers [ARBs], calcium channel blockers, and β-...
Source: Clinical Therapeutics - March 27, 2020 Category: Drugs & Pharmacology Authors: Boockvar KS, Song W, Lee S, Intrator O Tags: Clin Ther Source Type: research

Safety and Efficacy of Glycoprotein IIb/IIIa Inhibitors in Patients With Acute Myocardial Infarction in the Presence of Intracoronary Thrombus: An Analysis From the Grand Drug-Eluting Stent Registry.
This study, performed from January 1, 2004, to November 31, 2014, at 55 centers in Korea, was based on the Grand Drug-Eluting Stent registry, which is a Korean, nationwide, multicenter, pooled registry of drug-eluting stents. The registry enrolled all-comers without any exclusion criteria except patient withdrawal of consent. A total of 1329 patients with AMI who had an overt intracoronary thrombus at the initial coronary angiography were analyzed. The efficacy end point was a 1-year major adverse cardiovascular event, defined as a composite of all death, myocardial infarction, target lesion revascularization, and stent th...
Source: Clinical Therapeutics - March 26, 2020 Category: Drugs & Pharmacology Authors: Zheng C, Kang J, Yang HM, Han JK, Park KW, Kang HJ, Koo BK, Kim HS Tags: Clin Ther Source Type: research

Chronic Stress and Glucocorticoid Receptor Resistance in Asthma.
Abstract PURPOSE: Chronic and persistent exposure to negative stress can lead to adverse consequences on health. Particularly, psychosocial factors were found to increase the risk and outcome of respiratory diseases like asthma. Glucocorticoids (GCs) are the most efficient anti-inflammatory therapy for asthma. However, a significant proportion of patients don't respond adequately to GC administration. GC sensitivity is modulated by genetic and acquired disease-related factors. Additionally, it was proposed that endogenous corticosteroids may limit certain actions of synthetic GCs, contributing to insensitivity. Ps...
Source: Clinical Therapeutics - March 26, 2020 Category: Drugs & Pharmacology Authors: Palumbo ML, Prochnik A, Wald MR, Genaro AM Tags: Clin Ther Source Type: research

The Enhancing Quality of Prescribing Practices for Older Veterans Discharged From the Emergency Department (EQUIPPED) Potentially Inappropriate Medication Dashboard: A Suitable Alternative to the In-Person Academic Detailing and Standardized Feedback Reports of Traditional EQUIPPED?
We describe the development process of the EQUIPPED dashboard and the key audit and feedback components found within. METHODS: The Veterans Affairs (VA) Corporate Data Warehouse (CDW) serves as the underlying data source for the EQUIPPED dashboard. SQL Server Integration Services was used to build the backend data architecture. Data were isolated from the CDW for reporting purposes using an extract, load, transform (ELT) approach. The team used SQL Server Reporting Services to produce the user interface and add interactive functionality. The team used an agile development approach when designing the user interface, en...
Source: Clinical Therapeutics - March 25, 2020 Category: Drugs & Pharmacology Authors: Burningham Z, Jackson GL, Kelleher J, Stevens M, Morris I, Cohen J, Maloney G, Vaughan CP Tags: Clin Ther Source Type: research

Effect of 5- μg Dose of Dexmedetomidine in Combination With Intrathecal Bupivacaine on Spinal Anesthesia: A Systematic Review and Meta-analysis.
Effect of 5-μg Dose of Dexmedetomidine in Combination With Intrathecal Bupivacaine on Spinal Anesthesia: A Systematic Review and Meta-analysis. Clin Ther. 2020 Mar 25;: Authors: Liu S, Zhao P, Cui Y, Lu C, Ji M, Liu W, Jiang W, Zhu Z, Sun Q Abstract PURPOSE: Intrathecal dexmedetomidine (DEX) has been used to improve the quality and duration of spinal anesthesia. The aim of this meta-analysis is to evaluate whether intrathecal DEX could prolong the duration of sensory and motor block during spinal anesthesia. METHODS: We searched PubMed, EMBASE, Web of Science, and the Cochrane Library for rand...
Source: Clinical Therapeutics - March 25, 2020 Category: Drugs & Pharmacology Authors: Liu S, Zhao P, Cui Y, Lu C, Ji M, Liu W, Jiang W, Zhu Z, Sun Q Tags: Clin Ther Source Type: research

The Cost-Effectiveness of Eltrombopag for the Treatment of Immune Thrombocytopenia in the United States.
This study aimed to estimate the cost-effectiveness of treating ITP with a comparable thrombopoietin receptor agonist (eltrombopag vs romiplostim). METHODS: A Markov model was implemented over a lifetime time horizon to estimate the benefits and costs of each treatment. The model featured 3 health states based on current guidelines: (1) on treatment; (2) treatment failure/discontinuation; and (3) mortality. In line with therapeutic goals in ITP, model patients could experience 3 events: no bleeding, mild/moderate bleeding, or severe bleeding. Data on eltrombopag use were obtained from an open-label extension of previo...
Source: Clinical Therapeutics - March 18, 2020 Category: Drugs & Pharmacology Authors: Tremblay G, Dolph M, Roy AN, Said Q, Forsythe A Tags: Clin Ther Source Type: research