Ten Medication-Related Tips in Outpatient Practice.

Am J Med. 2017 Feb;130(2):146-147

Authors: Greenberg J

PMID: 27746292 [PubMed - indexed for MEDLINE]

Safety profile of the varicella vaccine (Oka vaccine strain) based on reported cases from 2005 to 2015 in Japan.

Vaccine. 2016 Sep 22;34(41):4943-4947

Authors: Yoshikawa T, Ando Y, Nakagawa T, Gomi Y

Abstract
BACKGROUND: As of 2014, routine vaccination strategies in Japan have included the varicella vaccine. Given the widespread use of the vaccine, it is important to investigate the safety profile of the vaccine strain, Oka/Biken varicella, in Japanese patients.
METHODS: Reports of adverse events associated with varicella vaccination between 2005 and 2015 were retrospectively reviewed. Virological analysis was performed on clinical specimens collected from some of the reported cases to determine whether the etiological agent was the wild-type or Oka vaccine-strains.
RESULTS: There were 351 reports (3.71/100,000 doses) of adverse events during the observation period. Among the 351 reports, there were 88 reports (0.93/100,000 doses) of varicella-like and 66 reports (0.70/100,000 doses) of zoster-like skin rashes. The wild-type strain induced varicella-like skin rashes earlier than the Oka vaccine strain. The Oka vaccine strain induced zoster-like skin rashes in younger patients compared to the wild-type strain. The onset of zoster-like skin rashes after vaccination was earlier in patients vaccinated with the Oka vaccine-type strain.
CONCLUSION: The Oka/Biken vaccine is generally safe and well tolerated in Japan. Clinical aspects of adverse reactions caused by the Oka vaccine strain were consistent with previous reports from the United States and Europe.

PMID: 27591104 [PubMed - indexed for MEDLINE]

Safety and Tolerability of Stribild in the Southeast United States.

J Int Assoc Provid AIDS Care. 2016 Sep;15(5):432-9

Authors: Derrick CB, Lu ZK, Caulder CR, Hester EK, Wagner TD, Bookstaver PB

Abstract
PURPOSE: The purpose of this study is to assess postmarketing safety and tolerability of Stribild (elvitegravir [EVG]/cobicistat [COBI]/tenofovir disoproxil fumarate [TDF]/emtricitabine [FTC]).
METHODS: A retrospective, pharmacoepidemiologic study in 2 outpatient HIV clinics in the Southeast United States was conducted among adults receiving EVG/COBI/TDF/FTC. We evaluated incidence and treatment-related adverse events, including change in serum creatinine (SCr).
RESULTS: Patients were primarily treatment experienced (n = 173, 60%), African American (n = 210, 73%), and males (n = 187, 65%). One hundred ninety-five (68%) patients had any increase in SCr, and 65 (23%) had an increase of ≥0.3 mg/dL. Mean SCr change from baseline to peak was 0.2 mg/dL. Being treatment experienced (odds ratio [OR] = 2.21, 95% confidence interval [CI]: 1.12-4.38) was associated with SCr ≥0.3 mg/dL, while body mass index ≥30 kg/m(2) (OR = 0.41, 95% CI: 0.18-0.93) was protective. Twenty (7%) patients discontinued therapy, 3 due to acute kidney injury.
CONCLUSION: Our results demonstrate limited adverse events and low discontinuation rates associated with EVG/COBI/TDF/FTC.

PMID: 27225853 [PubMed - indexed for MEDLINE]

13 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2017/12/06

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

13 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2017/12/06

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

12 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2017/12/05

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Pharmacogenetics: A strategy for personalized medicine for autoimmune diseases.

Clin Genet. 2017 Nov 30;:

Authors: Tavakolpour S, Darvishi M, Ghasemiadl M

Abstract
For many years, a considerable number of patients with autoimmune diseases (ADs) have suffered from a lack of drug response and drug-related toxicity. Despite the emergence of new therapeutic options such as biological agents, patients continue to struggle with these problems. Unfortunately, new challenges, including the paradoxical effects of biological drugs, have complicated the situation. In recent decades, efforts have been made to predict drug response as well as drug-related side-effects. Thanks to the many advances in genetics, evaluation of markers to predict drug response/toxicity before the initiation of treatment may be an avenue toward personalizing treatments. Implementing pharmacogenetics and pharmacogenomics in the clinic could improve clinical care; however, obstacles remain to effective personalized medicine for ADs. The present study attempted to clarify the concept of pharmacogenetics/pharmacogenomics for ADs. After an overview on the pathogenesis of the most common types of treatments, this paper focuses on pharmacogenetic studies related to the selected ADs. Bridging the gap between pharmacogenetics and personalized medicine is also discussed. Moreover, the advantages, disadvantages and recommendations related to making personalized medicine practical for ADs have been addressed.

PMID: 29194620 [PubMed - as supplied by publisher]

Longitudinal Study of Short-term Corticosteroid Use by Working-Age Adults with Diabetes Mellitus: Risks and Mitigating Factors.

J Diabetes. 2017 Nov 28;:

Authors: Rogers MAM, Lin P, Nallamothu BK, Kim C, Waljee AK

Abstract
BACKGROUND: We assessed the frequency of short-term oral corticosteroid use in adults with diabetes, and examined the incidence of fractures, venous thromboembolism (VTE) and hospitalization for sepsis after corticosteroid use. We also evaluated whether preventative medications mitigated adverse events.
METHODS: We conducted a longitudinal study of 1,548,945 adults (ages 18-64 years) who received healthcare coverage through a large national health insurer, years 2012-2014. Incidence rate ratios (IRR) were calculated using conditional Poisson regression.
RESULTS: Short-term oral corticosteroids were used by 23.9% of adults with type 2 diabetes, 20.8% with type 1, and 20.9% without diabetes during the 3-year period (p<0.001). Baseline risks of fracture, VTE, and sepsis were greater for individuals with diabetes than those without (p<0.001). The combined effect of having diabetes and using corticosteroids was greater than the sum of the individual effects (synergy indices of 1.17, 1.23, 1.30 for fracture, VTE and sepsis, respectively). The IRR for venous thromboembolism was 3.62 (95% CI, 2.41-5.45) in the 5-30 days after corticosteroid use. Fractures increased in the 5-30 days after corticosteroid use (IRR=2.06, 95% CI: 1.52, 2.80), but concomitant use of ergocalciferol mitigated this risk (IRR=1.13; 95% CI: 0.12, 11.07). The risk of hospitalization for sepsis was elevated with corticosteroid use (IRR=3.79; 95% CI: 2.05, 7.01) but was mitigated by the concomitant use of statins.
CONCLUSIONS: Short-term oral corticosteroid use is common in adults with diabetes and is associated with an elevated, but low, risk of adverse events. Our findings suggest that preventative medications may mitigate risk.

PMID: 29193668 [PubMed - as supplied by publisher]

The Yusuf-Peto method was not a robust method for meta-analyses of rare events data from antidepressant trials.

J Clin Epidemiol. 2017 Nov;91:129-136

Authors: Sharma T, Gøtzsche PC, Kuss O

Abstract
OBJECTIVES: The aim of the study was to identify the validity of effect estimates for serious rare adverse events in clinical study reports of antidepressants trials, across different meta-analysis methods.
STUDY DESIGN AND SETTING: Four serious rare adverse events (all-cause mortality, suicidality, aggressive behavior, and akathisia) were meta-analyzed using different methods. The Yusuf-Peto odds ratio ignores studies with no events and was compared with the alternative approaches of generalized linear mixed models (GLMMs), conditional logistic regression, a Bayesian approach using Markov Chain Monte Carlo (MCMC), and a beta-binomial regression model.
RESULTS: The estimates for the four outcomes did not change substantially across the different methods; the Yusuf-Peto method underestimated the treatment harm and overestimated its precision, especially when the estimated odds ratio deviated greatly from 1. For example, the odds ratio for suicidality for children and adolescents was 2.39 (95% confidence interval = 1.32-4.33), using the Yusuf-Peto method but increased to 2.64 (1.33-5.26) using conditional logistic regression, to 2.69 (1.19-6.09) using beta-binomial, to 2.73 (1.37-5.42) using the GLMM, and finally to 2.87 (1.42-5.98) using the MCMC approach.
CONCLUSION: The method used for meta-analysis of rare events data influences the estimates obtained, and the exclusion of double-zero event studies can give misleading results. To ensure reduction of bias and erroneous inferences, sensitivity analyses should be performed using different methods instead of the Yusuf-Peto approach, in particular the beta-binomial method, which was shown to be superior through a simulation study.

PMID: 28802674 [PubMed - indexed for MEDLINE]

Characterizing "Adversity" of Pathology Findings in Nonclinical Toxicity Studies: Results from the 4th ESTP International Expert Workshop.

Toxicol Pathol. 2016 Aug;44(6):810-24

Authors: Palazzi X, Burkhardt JE, Caplain H, Dellarco V, Fant P, Foster JR, Francke S, Germann P, Gröters S, Harada T, Harleman J, Inui K, Kaufmann W, Lenz B, Nagai H, Pohlmeyer-Esch G, Schulte A, Skydsgaard M, Tomlinson L, Wood CE, Yoshida M

Abstract
The identification of adverse health effects has a central role in the development and risk/safety assessment of chemical entities and pharmaceuticals. There is currently a need for better alignment regarding how nonclinical adversity is determined and characterized. The European Society of Toxicologic Pathology (ESTP) therefore coordinated a workshop to review available definitions of adversity, weigh determining and qualifying factors of adversity based on case examples, and recommend a practical approach to define and characterize adversity in toxicology reports, to serve as a valuable prerequisite for future organ- or lesion-specific workshops planned by the ESTP.

PMID: 27102650 [PubMed - indexed for MEDLINE]

13 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2017/12/01

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

65 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2017/11/29

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

65 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2017/11/29

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Dermatological Complications After Solid Organ Transplantation.

Clin Rev Allergy Immunol. 2017 Nov 25;:

Authors: Naldi L, Venturuzzo A, Invernizzi P

Abstract
Organ transplant recipients (OTRs) are a population at high risk for cutaneous adverse events. Their early recognition and appropriate treatment is an important component of the clinical management of OTRs and should be optimally dealt with by dermatologists working in the context of a transplant dermatology clinic. Skin examination should be a standard procedure before performing organ transplantation to assess conditions which may be difficult to manage after the transplant procedure has been performed or which may represent a contraindication to transplantation, e.g., malignant melanoma. It also offers an opportunity to educate patients on skin care after organ transplantation. Skin infections can occur at any time after organ transplantation and include viral, bacterial, and fungal opportunistic infections. The risk of reactivation of latent viruses, such as varicella-zoster virus (VZV) and cytomegalovirus (CMV), is high. Bacterial infections are frequent and may be caused by unusual agents such Actinomyces, Mycobacteria, Legionella, or Nocardia. A large spectrum of fungal infections may occur, ranging from superficial (e.g., dermatophytes) to deeper and more severe ones (Alternaria, Aspergillus, Cryptococcus, Histoplasma). Drug-related idiosyncratic reactions usually occur early after the introduction of the causative drug, e.g., hypersensitivity reaction to azathioprine. On the long-term run, cutaneous effects due to cumulative drug toxicity, e.g., sebaceous hyperplasia from cyclosporine, may appear. Rare immunologically driven inflammatory reactions may occur in OTRs such as GVH or autoimmune disease. Tumors are particularly frequent. Kaposi's sarcoma, associated with persistent human herpes virus 8 (HHV8) infection, and cutaneous anaplastic large-cell lymphoma (ALCL) occur early after transplantation. Other cancers, such as nonmelanoma skin cancer (NMSCs), associated with persistent human papillomavirus (HPV) infections, malignant melanoma, Merkel cell carcinoma, or adnexal tumors, manifest later with an incidence which is much higher than observed in the general population. The incidence increases further after a first NMSC occurs.

PMID: 29177692 [PubMed - as supplied by publisher]

Amiloride does not protect retinal nerve fibre layer thickness in optic neuritis in a phase 2 randomised controlled trial.

Mult Scler. 2017 Nov 01;:1352458517742979

Authors: McKee JB, Cottriall CL, Elston J, Epps S, Evangelou N, Gerry S, Kennard C, Kong Y, Koelewyn A, Kueker W, Leite MI, Palace J, Craner M

Abstract
BACKGROUND: Recent basic and clinical evidence suggests amiloride may be neuroprotective in multiple sclerosis (MS) through the blockade of the acid sensing ion channel (ASIC).
OBJECTIVE: To examine the neuroprotective efficacy of amiloride in acute optic neuritis (ON).
METHODS: A total of 48 patients were recruited to a phase 2, double blind, single site, randomised controlled trial. Scanning laser polarimetry (GDx) at 6 months was the primary outcome measure and optical coherence tomography (OCT) and visual and electrophysiological measures were secondary outcome measures. Participants aged 18-55 years, ≤28 days of onset of first episode unilateral ON, were randomised to amiloride (10 mg daily for 5 months) or placebo ( clinicaltrials.gov , NCT 01802489).
RESULTS: Intention-to-treat (ITT) cohort consisted of 43 patients; 23 placebo and 20 amiloride. No significant drug-related adverse events occurred. No significant differences were found in GDx ( p = 0.840). Visual evoked potentials (VEP) were significantly prolonged in the amiloride group compared to placebo ( p = 0.004). All other secondary outcome measures showed no significant difference. Baseline analysis of OCT data demonstrated a significant pre-randomisation thinning of ganglion cell layer.
CONCLUSION: Amiloride has not demonstrated any neuroprotective benefit within this trial paradigm, but future neuroprotective trials in ON should target the window of opportunity to maximise potential neuroprotective benefit.

PMID: 29172994 [PubMed - as supplied by publisher]

Olmesartan is not associated with the risk of enteropathy: a Korean nationwide observational cohort study.

Korean J Intern Med. 2017 Nov 27;:

Authors: You SC, Park H, Yoon D, Park S, Joung B, Park RW

Abstract
Background/Aims: Olmesartan, a widely used angiotensin II receptor blocker (ARB), has been linked to sprue-like enteropathy. No cases of olmesartan-associated enteropathy have been reported in Northeast Asia. We investigated the associations between olmesartan and other ARBs and the incidence of enteropathy in Korea.
Methods: Our retrospective cohort study used data from the Korean National Health Insurance Service to identify 108,559 patients (58,186 females) who were initiated on angiotensin converting enzyme inhibitors (ACEis), olmesartan, or other ARBs between January 2005 and December 2012. The incidences of enteropathy were compared among drug groups. Changes in body weight were compared after propensity score matching of patients in the ACEis and olmesartan groups.
Results: Among 108,559 patients, 31 patients were diagnosed with enteropathy. The incidences were 0.73, 0.24, and 0.37 per 1,000 persons, in the ACEis, olmesartan, and other ARBs groups, respectively. Adjusted rate ratios for enteropathy were: olmesartan, 0.33 (95% confidential interval [CI], 0.10 to 1.09; p = 0.070) and other ARBs, 0.34 (95% CI, 0.14 to 0.83; p = 0.017) compared to the ACEis group after adjustment for age, sex, income level, and various comorbidities. The post hoc analysis with matched cohorts revealed that the proportion of patients with significant weight loss did not differ between the ACEis and olmesartan groups.
Conclusions: Olmesartan was not associated with intestinal malabsorption or significant body weight loss in the general Korean population. Additional large-scale prospective studies of the relationship between olmesartan and the incidence of enteropathy in the Asian population are needed.

PMID: 29172402 [PubMed - as supplied by publisher]

Randomized, double-blind, placebo-controlled dose-finding study of the dipeptidyl peptidase-4 inhibitor linagliptin in pediatric patients with type 2 diabetes.

Pediatr Diabetes. 2017 Nov 24;:

Authors: Tamborlane WV, Laffel LM, Weill J, Gordat M, Neubacher D, Retlich S, Hettema W, Hoesl CE, Kaspers S, Marquard J

Abstract
OBJECTIVE: To identify the dose of the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin in pediatric patients with type 2 diabetes (T2D).
METHODS: Double-blind, randomized, controlled parallel group study comparing linagliptin 1 and 5 mg once daily, with placebo in 39 patients with T2D aged 10 to below 18 years. The primary efficacy endpoint was the change from baseline in glycated hemoglobin (HbA1c) after 12 weeks of treatment. The key pharmacodynamic endpoint was DPP-4 inhibition during steady-state.
RESULTS: Compared to placebo, there was a dose-dependent reduction in mean HbA1c of 0.48% and 0.63% with linagliptin 1 and 5 mg, respectively, associated with corresponding declines in mean fasting plasma glucose (FPG) of 5.6 and 34.2 mg/dL. Median DPP-4 inhibition was 38% with linagliptin 1 mg and 79% with linagliptin 5 mg. Geometric mean trough levels of linagliptin were 3.80 and 7.42 nmol/L in the 1 and 5 mg groups, respectively; levels that were slightly higher than in adult patients with T2D that were most likely caused by higher plasma DPP-4 concentrations in the study population. There were no drug-related adverse events during treatment with either dose of linagliptin.
CONCLUSIONS: Linagliptin was well tolerated and induced dose-dependent DPP-4 inhibition that was accompanied by corresponding reductions in HbA1c and FPG levels in young people with T2D. The results are consistent with the clinical efficacy and safety profile that have been reported for linagliptin in adult patients with T2D, favoring linagliptin 5 mg over 1 mg.

PMID: 29171139 [PubMed - as supplied by publisher]

11 Topical nsaids for analgesia in traumatic corneal abrasions: a systematic review and meta-analysis.

Emerg Med J. 2017 Dec;34(12):A868

Authors: Lawrenson A, Wakai A

Abstract
BACKGROUND: Traumatic corneal abrasions are common ocular presenTations in the ED. There is no consensus regarding the most appropriate analgesia for this condition. Topical non-steroidal anti-inflammatory drugs (NSAIDs) have been suggested as pain-relief to minimise systemic adverse events associated with oral analgesia.
AIM: To identify and evaluate all randomised controlled trials (RCTs) comparing the use of topical NSAIDs with placebo or any alternative analgesic interventions in adults with traumatic corneal abrasions (including corneal abrasions arising from foreign body removal), to reduce pain, and its effects on healing time.
METHODS: We searched MEDLINE, EMBASE, Cochrane Library and clinical trials registers up to 30/03/17. We did not use any date or language restrictions in the electronic searches for trials. We checked the reference lists of identified trials to search for further potentially relevant studies. Two review authors independently performed data extraction and assessed risks of bias in the included studies. We assessed risk of bias using the Cochrane risk of bias tool and rated the certainty of the evidence using GRADE.
RESULTS: We included nine studies that met the inclusion criteria, reporting data on 637 participants. These studies compared five types of topical NSAIDs (0.1% indomethacin, 0.03% flurbiprofen, 0.5% ketorolac, 1% indomethacin, 0.1% diclofenac) to control (consisting of standard care and in four studies used placebo eye drops). Overall, the studies were at an unclear or high risk of bias (particularly selection and reporting bias). None of the included studies reported the primary outcome measures of this review, namely participant-reported pain intensity reduction of 30% or more or 50% or more at 24 hours. Four trials, that included data on 481 participants receiving NSAIDs or control (placebo/standard care), reported on the use of 'rescue' analgesia at 24 hours as a proxy measure of pain control. Topical NSAIDs were associated with a reduction in the need for oral analgesia compared with control (risk ratio (RR) 0.46, 95% confidence interval (CI) 0.34 to 0.61; low-certainty evidence). Approximately 4 out of 10 people in the control group used rescue analgesia at 24 hours. No data were available on the use of analgesia at 48 or 72 hours. There was no evidence from the included trials of an effect of topical NSAIDS on healing time and possible drug-related adverse events were low and balanced across intervention and control groups.
CONCLUSIONS: The findings of the included studies do not provide strong evidence to support the use.

PMID: 29170308 [PubMed - in process]

[Unexpected adverse events of immunotherapies in non-small cell lung cancer: About 2 cases].

Rev Pneumol Clin. 2017 Nov 20;:

Authors: de Chabot G, Justeau G, Pinquié F, Nadaj-Pakleza A, Hoppé E, Hureaux J, Urban T

Abstract
Programmed death receptor 1 (PD1) checkpoint inhibitors are known for immune mediated toxicities such as colitis, endocrinopathies and pneumonitis. However, other rare adverse effects are reported in the literature. Nivolumab is an anti-PD1 immunotherapy used in the second line of non-small cell lung cancer (NSCLC). We report two cases of rare toxicities occurring under nivolumab in patients without a history of dysimmunity. A 79-year-old patient with a large-cell carcinoma showed a muscle weakness after the second course, revealing myositis with a CPK grade IV elevation as well as symptoms of myasthenia. The diagnosis of myositis was confirmed by a muscle biopsy. An 82-year-old patient followed for bronchial adenocarcinoma with EGFR mutation, presented with nivolumab shoulder and hip pain with extreme fatigue. After further investigations, the diagnosis of systemic erythematosus lupus was retained. Investigations led to the diagnosis of systemic lupus erythematosus. For both patients treatment was interrupted and systemic corticosteroid therapy was initiated permitting resolution of symptoms. The occurrence of symptoms of dysimmunity should attract the attention of the clinician, leading to discontinuation of anti-PD1 therapy and corticosteroid therapy. Retreatment after symptoms resolution must be collegially discussed if no alternative therapeutic is available.

PMID: 29169677 [PubMed - as supplied by publisher]

Pharmacogenetics of Methadone Response.

Mol Diagn Ther. 2017 Nov 22;:

Authors: Fonseca F, Torrens M

Abstract
The efficacy of methadone maintenance treatment (MMT) in opioid use disorder is well established but responses vary. The influence of methadone pharmacodynamics and pharmacokinetics on dose requirements and program outcomes remains controversial despite the increasing number of studies evaluating genetic influences on response to methadone treatment. Furthermore, patients require different doses (usually between 60 and 100 mg/day), and there are no clear data on a plasma concentration associated with treatment success. We review the evidence regarding the influence of genetics on pharmacokinetic and pharmacodynamic factors in terms of MMT outcome. We also analyse the influence of genetics on the occurrence of severe adverse events such as respiratory depression and ventricular arrhythmia in methadone treatment. The outcomes of MMT may be influenced by a combination of environmental, drug-induced, and genetic factors. The influence of pharmacokinetic genetic variability can be clinically managed by modifying the posology. A better understanding of pharmacodynamic factors could help in selecting the best opioid for substitution treatment, but patient phenotype must still be considered when establishing a maintenance treatment. Pharmacogenetic studies represent a promising field that aims to individualize treatments according to genetic backgrounds, adapting medication and doses according to possible outcomes and the risk of adverse events.

PMID: 29168075 [PubMed - as supplied by publisher]