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Clin Drug Investig 2019 Apr 16. Epub 2019 Apr 16.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.

Background And Objective: Sodium glucose co-transporter 2 inhibitors increase urinary glucose excretion and reduce visceral adiposity and body weight, but their efficacy on patients with nonalcoholic fatty liver disease has not been sufficiently investigated. The aim of this study was to assess the effect of sodium glucose co-transporter 2 inhibitors on liver fat mass and body composition in patients with nonalcoholic fatty liver disease and type 2 diabetes mellitus.

Methods: We retrospectively analyzed 17 patients with nonalcoholic fatty liver disease and type 2 diabetes who received sodium glucose co-transporter 2 inhibitors between November 2016 and July 2017. Read More

Clin Drug Investig 2019 Apr 11. Epub 2019 Apr 11.

Imperial College Healthcare NHS Trust, London, UK.

Background And Objective: Integrase strand transfer inhibitors (INSTIs) have become the preferred first-line antiretroviral therapy in adults. There is paucity of published data on their use in children outside of clinical trials, particularly long-term safety and tolerability. This study aimed to describe INSTI use including the number of, and reasons for INSTI discontinuation. Read More

Clin Drug Investig 2019 Apr 11. Epub 2019 Apr 11.

Department of Cardiology, Freeman Hospital, Newcastle University, Newcastle upon Tyne, UK.

Patients with acute coronary syndrome (ACS) require long-term antithrombotic intervention to reduce the risk of further ischemic events; dual antiplatelet therapy with a P2Y inhibitor and acetylsalicylic acid (ASA) is the current standard of care. However, pivotal clinical trials report that patients receiving this treatment have a residual risk of approximately 10% for further ischemic events. The development of non-vitamin K antagonist oral anticoagulants (NOACs) has renewed interest in a 'dual pathway' strategy, targeting both the coagulation cascade and platelet component of thrombus formation. Read More

Clin Drug Investig 2019 Apr 2. Epub 2019 Apr 2.

Rheumatology Unit, Department of Emergency and Organ Transplantation, University of Bari, Pz. G. Cesare, 11, 70124, Bari, Italy.

Background: Identification of predictors of clinical response to certolizumab-pegol (certolizumab) may aid the decision-making process for treating patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA).

Objective: The aim of our study was to evaluate the effectiveness of certolizumab and identify any predictors of favorable outcome in patients with RA, PsA, or SpA.

Methods: We studied 355 RA, SpA, and PsA patients starting treatment with certolizumab. Read More

Clin Drug Investig 2019 Apr 1. Epub 2019 Apr 1.

Division of Oncology, S.Orsola-Malpighi Hospital, Bologna, Italy.

Management of metastatic renal cell carcinoma has drastically changed in the last few years, witnessing the advent of more and more target therapies and, recently, of immune-checkpoint inhibitors. On the other hand, the adjuvant setting still lacks a clear beneficial treatment. Medical treatment still remains a compelling challenge. Read More

Clin Drug Investig 2019 Mar 26. Epub 2019 Mar 26.

National Institute of Oncology, Rath Gy. u. 7-9, 1122, Budapest, Hungary.

Background: Sunitinib is still one of the standard therapies in metastatic renal cell carcinoma (mRCC). Despite the benefit of sunitinib resistance will develop in the majority of patients. Most of them receive multiple sequential therapies during the course of disease. Read More

Clin Drug Investig 2019 Mar 21. Epub 2019 Mar 21.

Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, 335 Sutherland Drive, Room 209 Salk Pavilion, Pittsburgh, PA, 15261, USA.

Background: Depression and coronary artery disease (CAD) are leading causes of death and disability and commonly co-occur. Different antidepressant classes have similar efficacy for depressed patients with CAD, but cardiovascular implications are unclear. Selective serotonin reuptake inhibitors (SSRIs) and mirtazapine are first-line options for depressed patients with CAD. Read More

Clin Drug Investig 2019 Apr;39(4):419

Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.

The article Neratinib in Early-Stage Breast Cancer: A Profile of Its Use in the EU, written by Sohita Dhillon, was originally published Online First without open access. Read More

Clin Drug Investig 2019 Mar 20. Epub 2019 Mar 20.

Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA, USA.

The original version of this article unfortunately contained a mistake. Read More

Clin Drug Investig 2019 Mar 19. Epub 2019 Mar 19.

Clinical Research, Alkermes, Inc., Waltham, MA, USA.

Background: A combination of the atypical antipsychotic olanzapine and opioid receptor antagonist samidorphan (OLZ/SAM) is in development for the treatment of schizophrenia. The goal of OLZ/SAM is to provide the antipsychotic efficacy of olanzapine while mitigating olanzapine-induced weight gain and many associated long-term metabolic consequences. The primary metabolic pathways for olanzapine are direct glucuronidation via uridine 5'-diphospho-glucuronosyltransferase (UGT)1A4 and cytochrome P450 (CYP)-mediated oxidation, mainly by CYP1A2. Read More

Clin Drug Investig 2019 Mar 18. Epub 2019 Mar 18.

Department of Anesthesiology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, 77 Goodell Street, Suite 550, Buffalo, NY, 14203, USA.

Background And Objective: The use and range of indications for anticoagulation therapy are steadily growing. The objective of this study was to develop a scoring model to predict the occurrence of significant bleeding in patients taking warfarin with a supra-therapeutic international normalized ratio.

Methods: Data were collected from the medical records of patients taking warfarin with an international normalized ratio > 3. Read More

Clin Drug Investig 2019 Mar 18. Epub 2019 Mar 18.

Department of Clinical Medicine (Pharmaceutical Medicine), Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.

Background And Objective: The results of large placebo-controlled clinical trials to evaluate cardiovascular risks associated with drugs for type 2 diabetes mellitus indicated different cardiovascular effects among these drugs, but the detailed design of each trial was not completely the same. The aim of this study was to perform time-matched evaluation of cardiovascular risks of drugs for type 2 diabetes.

Methods: We used the difference in restricted mean survival time (RMST) as a measure of cardiovascular risks. Read More

Clin Drug Investig 2019 Apr;39(4):411-418

Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.

The sufentanil 30 μg sublingual tablet (hereafter referred to as the sufentanil ST) is approved in the EU for acute moderate to severe pain in adults (Dzuveo™) and in the USA for acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate (Dsuvia™). It is a single-strength tablet housed in a single-dose applicator (which may minimize the likelihood of dosing errors) and is strictly for use in medically supervised/monitored settings. It is administered by a healthcare professional and has a minimum re-dose interval of 1 h and no drug delivery setup requirements. Read More

Clin Drug Investig 2019 Mar 13. Epub 2019 Mar 13.

Maccabi-Khan Institute of Research and Innovation, 4 Koifman St, 8th floor, 6812509, Tel Aviv, Israel.

Background: Most patients with Parkinson's disease exhibit intracellular accumulation of the α-synuclein protein encoded by the α-synuclein gene. It was recently shown that β-adrenoreceptor agonists downregulate this gene, decreasing the apparent risk of Parkinson's disease by up to 40%. In contrast, exposure to β-blocking drugs increases production of the α-synuclein protein. Read More

Clin Drug Investig 2019 Mar 9. Epub 2019 Mar 9.

Health Search, Italian College of General Practitioners and Primary Care, Via Sestese,61, 50141, Florence, Italy.

Background And Objectives: In 2014, the Italian Medicines Agency (AIFA) amended the summary of product characteristics of codeine-containing medications limiting their use for maximum three days. This study attempted to clarify the impact of AIFA intervention on prescribing trends and appropriateness of use of codeine-containing medications and other opioids.

Methods: Using the Health Search Database, a quasi-experimental interrupted time series analysis was conducted to evaluate changes in prescribing trends and appropriateness of use of codeine-containing medications and opioids between 2013 and 2015. Read More

Clin Drug Investig 2019 Mar 8. Epub 2019 Mar 8.

Department of Pharmacy Practice, School of Pharmacy, Texas Tech University Health Sciences Center, 1718 Pine Street, Abilene, TX, 79601, USA.

Background: Sepsis and septic shock are inflammatory disorders associated with high rates of mortality. Patients with sepsis and septic shock frequently become tachycardic as a result of the utilization of vasopressor therapy and cardiac overcompensation owing to hypotension, predisposing patients to an increased risk of atrial fibrillation. Previously, it was thought that beta-blocker therapy in patients with sepsis would exacerbate hypotension; however, recent studies have shown that may not be the case. Read More

Clin Drug Investig 2019 Mar 7. Epub 2019 Mar 7.

University Department Pro.Sa.M.I, "G. D'Alessandro", University of Palermo, Via dei Benedettini, 1, 90134, Palermo, Italy.

Systemic juvenile idiopathic arthritis (sJIA) is an autoinflammatory disease characterised by fever and arthritis. We describe the case of a 14-year-old girl hospitalised with fever associated with rash, myalgia, arthralgia and polyarticular involvement. Examinations revealed increased levels of C-reactive protein, erythrocyte sedimentation rate, ferritin, triglycerides, leukocytes, neutrophils, lactate dehydrogenase, fibrinogen, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT). Read More

Clin Drug Investig 2019 Apr;39(4):407-410

Princess Alexandra Hospital, 199 Ipswich Road, Woolloongabba, Brisbane, QLD, 4102, Australia.

Oral antipsychotics are used to treat motor and behavioural disturbances in Huntington's disease (HD). However, patients with behavioural disturbances are often non-compliant, thus the oral route is inappropriate. The effects of antipsychotic long-acting injections (LAI) in HD are significantly underrepresented in literature. Read More

Clin Drug Investig 2019 Feb 27. Epub 2019 Feb 27.

Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA, USA.

Background And Objectives: Suvorexant is an orexin receptor antagonist indicated for the treatment of insomnia, characterized by difficulties with sleep onset and/or sleep maintenance. As suvorexant is metabolized primarily by Cytochrome P450 3A (CYP3A), and its pharmacokinetics may be affected by CYP3A modulators, the effects of CYP3A inhibitors (ketoconazole or diltiazem) or an inducer (rifampin [rifampicin]) on the pharmacokinetics, safety, and tolerability of suvorexant were investigated.

Methods: In two Phase I, open-label, fixed-sequence trials (Studies P008 and P038), healthy subjects received a single oral dose of suvorexant followed by co-administration with multiple once-daily doses of strong/moderate CYP3A inhibitors (ketoconazole/diltiazem) or a strong CYP3A inducer (rifampin). Read More

Clin Drug Investig 2019 Feb 26. Epub 2019 Feb 26.

Department of Rheumatology, Korea University College of Medicine, Seoul, Korea.

Background: Tofacitinib and apremilast have shown considerable efficacy in placebo-controlled trials of active psoriatic arthritis, but the relative efficacy and safety remain unclear because of a lack of head-to-head comparisons.

Objective: The aim of this study was to assess the relative efficacy and safety of tofacitinib and apremilast at different doses in patients with active psoriatic arthritis.

Method: We performed a Bayesian network meta-analysis to combine evidence from randomized controlled trials for examination of the efficacy and safety of tofacitinib 10 mg, tofacitinib 5 mg, apremilast 30 mg, and apremilast 20 mg in psoriatic arthritis. Read More

Clin Drug Investig 2019 Feb 25. Epub 2019 Feb 25.

Department of Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Würzburg, Margarete-Höppel-Platz 1, 97080, Würzburg, Germany.

Lithium is a well established therapeutic agent in the treatment of uni- and bipolar affective disorders. Angiotensin-converting enzyme (ACE) inhibitors are the most frequently used class of drugs in the treatment of cardiovascular diseases. Combination therapy with both may be considered in clinical practice on occurrence of arterial hypertension after years of successful lithium therapy, yet an increased risk of lithium intoxication in combination with ACE inhibitors has been described and thus the combination has been warned against. Read More

Clin Drug Investig 2019 Apr;39(4):401-405

School of Pharmacy and Medical Sciences, University of Bradford, Bradford, BD7 1DP, UK.

Background And Objective: In England, the uptake of direct oral anticoagulants (DOACs) for stroke prevention in atrial fibrillation has been slow and varied across different Clinical Commissioning Groups (CCGs). This study aimed to profile the prescribing of oral anticoagulants for stroke prevention in patients with atrial fibrillation over 3 years in a CCG without restrictions to DOACs use to understand more about organisational and/or individual barriers to the early uptake of DOACs.

Methods: Data were collected from nine general practices between 1 April 2012 and 31 March 2015 of patients who were initiated on the oral anticoagulant therapy. Read More

Clin Drug Investig 2019 Apr;39(4):385-393

Cardiology Department, Asklepieion General Hospital, 1 Vasileos Pavlou Ave, Voula, 16673, Athens, Greece.

Background: Despite the overwhelming evidence and the established benefits of antihypertensive treatment, adherence to treatment remains low.

Objective: To assess the adherence to treatment with a perindopril/indapamide/amlodipine single-pill combination (SPC), its effectiveness on blood pressure (BP) reduction, as well as the safety and tolerability of this SPC over a 4-month treatment period.

Methods: This multicenter, non-interventional study prospectively included 2285 hypertensive patients on perindopril/indapamide/amlodipine SPC. Read More

Clin Drug Investig 2019 Apr;39(4):379-384

BCN Health Economics and Outcomes Research S.L., Barcelona, Spain.

Background: Phenylketonuria is a well-known rare disease included in the neonatal screening of many countries. Therefore, there are few published data on the admissions and costs of phenylketonuria in Spain.

Objective: The objective of this study was to assess the number of admissions and the economic burden of phenylketonuria in Spain. Read More

Clin Drug Investig 2019 Apr;39(4):341-353

Department of Pathology, School of Basic Medical Science, Wuhan University, 185 Donghu Road, Medical Building 8, 10th Floor, Wuchang District, Wuhan, 430071, Hubei, People's Republic of China.

Lung cancer is the most prevalent and deadly cancer worldwide. Immune checkpoint therapy, which targets regulatory pathways in T cells to boost anti-tumor immune response, has revolutionized lung cancer treatment paradigms. Inhibitors of the most established immune checkpoints such as programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) have been approved by the US Food and Drug Administration in the management of lung cancer. Read More

Clin Drug Investig 2019 Apr;39(4):395-400

Department of Obstetrics and Gynecology, Toho University Faculty of Medicine, 6-11-1 Omorinishi, Ota-ku, Tokyo, 143-8541, Japan.

Background And Objective: Administration of bevacizumab to ovarian cancer patients with distal deep vein thrombosis (DVT) is problematic because of lack of evidence about the likely outcomes. We conducted a preliminary study in ovarian cancer patients with DVT who received bevacizumab combined with a direct oral anticoagulant (DOAC).

Methods: We retrospectively investigated patients with advanced or recurrent epithelial ovarian cancer and distal DVT diagnosed by ultrasonography who underwent chemotherapy containing bevacizumab (15 mg/kg every 3 weeks) combined with DOAC therapy. Read More

Clin Drug Investig 2019 Apr;39(4):369-377

Department of Rheumatology and Immunology, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, People's Republic of China.

Background And Objective: Loxoprofen (LOX) is a nonsteroidal anti-inflammatory drug (NSAID). Although oral administration of LOX has been widely prescribed, clinical guidelines for osteoarthritis generally recommend topical rather than oral NSAIDs in specific patients. However, there is limited information on the effects of loxoprofen sodium oral (LOX-O) versus loxoprofen sodium hydrogel transdermal patch (LOX-T) in myalgia patients. Read More

Clin Drug Investig 2019 02;39(2):231

Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.

An Online First version of this article was made available online at. Read More

Clin Drug Investig 2019 02;39(2):215

Pharmacovigilance and Epidemiology Department, European Medicines Agency, London, UK.

The article Relative and Absolute Risk of Tendon Rupture with Fluoroquinolone and Concomitant Fluoroquinolone/Corticosteroid Therapy: Population-Based Nested Case-Control Study, written by Morales DR, Slattery J, Pacurariu A, Pinheiro L, McGettigan P, Kurz X, was originally published Online First without open access. Read More

Clin Drug Investig 2019 Apr;39(4):355-362

Department of Clinical Sciences and Community Health, Laboratory of Medical Statistics, Epidemiology, and Biometry G. A. Maccacaro, University of Milan, via Vanzetti 5, 20133, Milan, Italy.

Background And Objectives: Warfarin-related nephropathy is an unexplained acute kidney injury, and may occur in patients with supratherapeutic INR, in the absence of overt bleeding. Similar findings have been observed in rats treated with dabigatran etexilate. We conducted a prospective study in dabigatran etexilate-treated patients to assess the incidence of dabigatran-related nephropathy and to investigate the possible correlation between dabigatran plasma concentration (DPC) and worsening renal function. Read More

Clin Drug Investig 2019 Apr;39(4):363-368

Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan.

Background And Objective: Adverse cutaneous drug reactions associated with antiepileptic drugs (AEDs) are a serious problem in the clinical setting. New-generation AEDs have been reported to be better tolerated than old-generation forms; however, information about the risks of adverse cutaneous drug reactions to new-generation AEDs is limited.

Objective: The purpose of this study was to clarify the association of AEDs with adverse cutaneous drug reactions using a spontaneous reporting database. Read More

Clin Drug Investig 2019 Mar;39(3):331-340

Pharmerit (Shanghai) Company Limited, Shanghai, China.

Background And Objective: Teriflunomide is a once-daily oral immunomodulatory agent approved in 80 countries for the treatment of patients with relapsing multiple sclerosis (RMS). The study objective was to estimate the cost effectiveness of teriflunomide (14 mg tablet, daily) versus interferon beta-1b (250 mcg subcutaneous injection, every other day) among RMS patients from the Chinese healthcare system perspective.

Methods: A Markov model with annual cycles and a lifetime horizon was utilized to assess cost-effectiveness of teriflunomide in comparison with interferon beta-1b in RMS patients. Read More

Clin Drug Investig 2019 Mar;39(3):253-273

Research Department, East London NHS Foundation Trust, London, UK.

BACKGROUND AND OBJECTIVE: Individuals with severe mental illness experience increased morbidity and mortality as a result of metabolic problems that may partly be related to the adverse effects of antipsychotics. Compared with first-generation antipsychotics, second-generation antipsychotics collectively are considered to have stronger associations with lipid abnormalities, but evidence for this specific claim has not been systematically reviewed. The objective of this review was to evaluate the risk of dyslipidaemia with second-generation versus first-generation antipsychotics amongst individuals with severe mental illness. Read More

Clin Drug Investig 2019 Mar;39(3):319-330

Department of Pharmacy, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatric, Chongqing, 400014, China.

Background And Objective: Immune checkpoint inhibitors (ICIs)-cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death receptor-1 (PD-1) monoclonal antibodies (mAbs)-either as single agents or in combination have become the standard of care for an increasing number of indications. Understanding both the ICI-associated adverse events (AEs) and the possible rank-order of these drugs in terms of susceptibility is essential if we are to improve the curative effect and reduce toxicity.

Methods: We detected signals of the AEs of ICIs by data mining using the US Food and Drug Administration (FDA) AEs Reporting System (FAERS) database. Read More

Clin Drug Investig 2019 Mar;39(3):309-317

Pharma Medica Research Inc., 6100 Belgrave Road, Mississauga, ON, L5R 0B7, Canada.

Background And Objective: Following oral administration of abiraterone acetate, the parent compound abiraterone acetate is rapidly metabolized to abiraterone. To our knowledge, bioanalytical methods to date have not been able to detect the parent compound in human plasma, and bioassay was only performed on the metabolite. A highly sensitive bioanalytical method was developed and validated to measure plasma concentrations of the parent compound. Read More

Clin Drug Investig 2019 01;39(1):115

Health Intervention and Technology Assessment Program, Ministry of Public Health, Nonthaburi, Thailand.

The Open Access license, which previously read. Read More

Clin Drug Investig 2019 Mar;39(3):233-239

Dermatology, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.

Androgenetic alopecia (AGA) is characterized by non-scarring follicle miniaturization. Despite the success of approved therapies, commonly reported side effects and the need for continual use has led to the investigation of alternative therapies. The aim of this paper is to critically review the success of off-label, topical monotherapies for treatment of AGA in men. Read More

Clin Drug Investig 2019 01;39(1):113

Department of Gynaecology and Obstetrics, University Hospitals Leuven, KU Leuven, University of Leuven, Herestraat 49, 3000, Louvain, Belgium.

Dr. Arteaga serves on an Advisory Board for Novartis and was a consultant for AstraZeneca from 2015 to 2016. All other authors declare that they have no competing interests. Read More

Clin Drug Investig 2019 Mar;39(3):301-308

Department of Pharmacy Services, McGill University Health Centre, Montréal, Québec, Canada.

Background: As an increasing number of elderly are undergoing orthopaedic procedures, it is important to understand and evaluate postoperative pain management in this population, especially in regard to opioid use. Data in the literature pertaining to the very elderly remains scarce.

Objectives: This study was conducted to evaluate whether older patients require lower opioid doses than their younger counterparts after undergoing an elective or urgent orthopaedic procedure, and to assess the cumulative incidence of adverse events and length of stay for each age group. Read More

Clin Drug Investig 2019 Mar;39(3):241-252

Department of Dermatology, Fukushima Medical University, Hikarigaoka 1, Fukushima, 960-1295, Japan.

Palmoplantar pustulosis (PPP) is a chronic inflammatory disorder characterized by sterile pustules predominantly involving the palms and soles. The purpose of this review was to describe the characteristics of Japanese PPP patients as PPP is frequently observed within the Japanese population. Most Japanese dermatologists consider PPP a distinct entity, and co-existence of PPP and psoriasis is rare; however, outside Japan, PPP is often considered to be palmoplantar psoriasis, and an extra-palmoplantar lesion associated with PPP is considered to be psoriasis. Read More

Clin Drug Investig 2019 Jan;39(1):105-107

Zydus Research Centre, a Division of Cadila Healthcare Ltd, Sarkhej-Bavla NH 8A, Moraiya, Ahmedabad, Gujarat, 382 210, India.

Clin Drug Investig 2019 Jan;39(1):109-111

Division of Nephrology, Endocrinology, and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara-shi, Kanagawa, 259-1193, Japan.

Clin Drug Investig 2019 Mar;39(3):275-283

Department of Cardiology, Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), C/ Maestro Alonso s/n, 03010, Alicante, Spain.

Background And Objective: Dual antiplatelet therapy is one of the main treatments in acute coronary syndrome (ACS). Switching antiplatelet agents may be necessary in some patients to improve efficacy or safety. The objective of this study was to determine the prevalence, predictors, and implications of clinical switching in patients during hospital admission and 1-year follow-up at discharge. Read More

Clin Drug Investig 2019 Mar;39(3):285-299

Department of Pharmaceutical Sciences, Gatton College of Pharmacy, East Tennessee State University, Box 70594, Johnson City, TN, 37614-1708, USA.

Background And Objectives: Integrase strand transfer inhibitors (INSTIs), dolutegravir, elvitegravir, and raltegravir, have become integral in the treatment of HIV, with close monitoring of continued efficacy and tolerability. As side effect occurrence varies among subjects receiving these drugs, we sought to perform an exploratory analysis examining the role of several single-nucleotide polymorphisms (SNPs) on drug concentration changes, selected clinical outcomes, and the occurrence of subject-reported adverse events.

Methods: Adults (aged ≥ 18 years) receiving INSTI-based regimens for treatment of HIV were recruited and genotyped with an iPLEX ADME PGx Pro v1. Read More

Clin Drug Investig 2019 Feb;39(2):221-229

Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.

Neratinib (Nerlynx) is an oral, irreversible pan-human epidermal growth factor receptor (HER) tyrosine kinase inhibitor of HER1, HER2 and HER4. Neratinib therapy for 12 months significantly reduced the risk of invasive disease recurrence or death relative to placebo at both 2 and 5 years post-randomization in the pivotal ExteNET trial in women with early-stage HER2-positive breast cancer who had completed adjuvant trastuzumab. Subgroup analyses showed that patients with hormone receptor (HRc)-positive disease derived greater benefit with neratinib than patients with HRc-negative disease, and patients who initiated neratinib within 1 year of completing trastuzumab had better outcomes than those who started treatment 1-2 years after trastuzumab. Read More

Clin Drug Investig 2019 Feb;39(2):117-139

School of Public Health and Health Systems, University of Waterloo, Waterloo, Canada.

Psychotropic medications and alcohol are potential risk factors for falls in older adults. However, there has been no appraisal of the literature on whether these medications, both singly and in combination with alcohol, are associated with falls in community dwelling older adults (those aged 60 years and older living independently without care). Four databases (PubMed, EMBASE, CINAHL and SCOPUS) and the grey literature (i. Read More

Clin Drug Investig 2019 Feb;39(2):187-195

Center for Primary Health Care Research, Lund University, Malmö, Sweden.

Background And Objective: The possible adverse or positive effects of levothyroxine treatment among patients with atrial fibrillation have been debated. Atrial fibrillation, levothyroxine treatment, and dementia are common among older adults, yet little is known about the effects of levothyroxine on the development of dementia.

Methods: The study population included all adults (n = 12,057) aged ≥ 45 years with a diagnosis of atrial fibrillation at 75 primary care centers in Sweden during 2001-2007 without an earlier recorded dementia diagnosis. Read More

Clin Drug Investig 2019 Feb;39(2):169-178

Department of Neuroscience, "Rita Levi Montalcini", University of Turin, Turin, Italy.

BACKGROUND AND OBJECTIVE: Clinical practice guidelines recommend antipsychotic monotherapy, including oral and long-acting formulations, in the treatment of schizophrenia. This open-label, randomized, controlled trial aimed to evaluate the efficacy and tolerability in patients with schizophrenia of once-monthly long-acting paliperidone palmitate (PP1M) compared with oral paliperidone extended release (ER), with a particular focus on satisfaction, subjective well-being, and service engagement.

Methods: Seventy-two consecutive outpatients with schizophrenia (DSM-5) were randomly assigned for 6 months to: (1) PP1M (50-150 mg equivalent) or (2) paliperidone ER (6-12 mg/day). Read More

Clin Drug Investig 2019 Feb;39(2):179-186

Department of Clinical Medicine (Pharmaceutical Medicine), Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.

Background And Objective: Empagliflozin and canagliflozin decreased the risk of major adverse cardiovascular events (MACE) compared with placebo in randomized clinical trials which were conducted to evaluate their cardiovascular risks. However, canagliflozin increased the risks of amputation and bone fracture, and the reasons for these observed differences remain unclear. The objective of this study was to evaluate the safety risks, specifically the risks of amputation and bone fracture, associated with sodium-glucose cotransporter 2 (SGLT2) inhibitors by using the difference in restricted mean survival time (RMST), an alternative measure to the hazard ratio. Read More

Clin Drug Investig 2019 01;39(1):103

Department of Clinical and Experimental Medicine, University Hospital of Messina, Messina, Italy.

Catalano Antonino, Martino Gabriella, Bellone Federica, Papalia Maria, Lasco Carmen, Basile Giorgio, Sardella Alberto, Nicocia Giacomo, Morabito Nunziata, Lasco Antonino. Read More