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")

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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]

Risk factors for QTc interval prolongation.

Eur J Clin Pharmacol. 2017 Nov 22;:

Authors: Heemskerk CPM, Pereboom M, van Stralen K, Berger FA, van den Bemt PMLA, Kuijper AFM, van der Hoeven RTM, Mantel-Teeuwisse AK, Becker ML

Abstract
PURPOSE: Prolongation of the QTc interval may result in Torsade de Pointes, a ventricular arrhythmia. Numerous risk factors for QTc interval prolongation have been described, including the use of certain drugs. In clinical practice, there is much debate about the management of the risks involved. In this study, we quantified the effect of these risk factors on the length of the QTc interval.
METHODS: We analyzed all ECGs that were taken during routine practice between January 2013 and October 2016 in the Spaarne Gasthuis, a general teaching hospital in the Netherlands. We collected laboratory values in the week before the ECG recording and the drugs prescribed. For the identification of risk factors, we used multilevel linear regression analysis to correct for multiple ECG recordings per patient.
RESULTS: We included 133,359 ECGs in our study, taken in 40,037 patients. Patients using one QT-prolonging drug had a 11.08 ms (95% CI 10.63-11.52; p < 0.001) longer QTc interval. Patients using two QT-prolonging drugs had a 3.04 ms (95% CI 2.06-4.02; p < 0.001) increase in the QTc interval compared to patients using one QT-prolonging drug. Women had a longer QTc interval compared to men (16.30 ms 95% CI 14.59-18.01; p < 0.001). The QTc interval increased with increasing age, but the difference between men and women diminished. Other independent risk factors that significantly prolonged the QTc interval with at least 10 ms were hypokalemia, hypocalcemia, and the use of loop diuretics.
CONCLUSION: We identified and quantified various risk factors for QTc interval prolongation.

PMID: 29167918 [PubMed - as supplied by publisher]

Development and validation of a complexity score to rank hospitalized patients at risk for preventable adverse drug events.

Am J Health Syst Pharm. 2017 Dec 01;74(23):1970-1984

Authors: Winterstein AG, Staley B, Henriksen C, Xu D, Lipori G, Jeon N, Choi Y, Li Y, Hincapie-Castillo J, Soria-Saucedo R, Brumback B, Johns T

Abstract
PURPOSE: The development of risk models for 16 preventable adverse drug events (pADEs) and their aggregation into the final complexity score (C-score) are described.
METHODS: Using data from 2 tertiary care facilities, logistic regression models were constructed for the first 5 hospital days that admissions were at risk for each of 16 pADEs. The best model for each pADE was validated in 100 bootstrap samples. The C-score was then aggregated and predicted individual pADE risk as the probability to develop at least 1 pADE. Using the 100 bootstrap samples for each pADE, 100 C-scores for validation were generated.
RESULTS: We utilized electronic health records (EHR) data from 65,518 admissions to UF Health Shands and 18,269 admissions to UF Health Jacksonville to develop risk models for 16 pADEs. Most models had very strong discriminant validity (C-statistic > 0.8), with the highest predicted decile representing about half of manifest pADEs. Among admissions in the highest C-score decile, about two thirds experienced at least 1 pADE (C-statistic, 0.838; 95% confidence interval, 0.838-0.839). C-score precision, defined as the percentage of patients consistently (i.e., at least 95 of 100 samples) ranked in the 90th percentile, was 80-84%.
CONCLUSION: The C-score was developed and validated for the identification of hospitalized patients at highest risk for pADEs. Aggregation of individual prediction models into a single score reduced its predictive power for most pADEs, compared with the individual risk models, but concentrated in the highest C-score decile a patient group more than two thirds of whom experienced at least 1 pADE.

PMID: 29167139 [PubMed - in process]

Biomaterials and Advanced Technologies for Hemostatic Management of Bleeding.

Adv Mater. 2017 Nov 22;:

Authors: Hickman DA, Pawlowski CL, Sekhon UDS, Marks J, Gupta AS

Abstract
Bleeding complications arising from trauma, surgery, and as congenital, disease-associated, or drug-induced blood disorders can cause significant morbidities and mortalities in civilian and military populations. Therefore, stoppage of bleeding (hemostasis) is of paramount clinical significance in prophylactic, surgical, and emergency scenarios. For externally accessible injuries, a variety of natural and synthetic biomaterials have undergone robust research, leading to hemostatic technologies including glues, bandages, tamponades, tourniquets, dressings, and procoagulant powders. In contrast, treatment of internal noncompressible hemorrhage still heavily depends on transfusion of whole blood or blood's hemostatic components (platelets, fibrinogen, and coagulation factors). Transfusion of platelets poses significant challenges of limited availability, high cost, contamination risks, short shelf-life, low portability, performance variability, and immunological side effects, while use of fibrinogen or coagulation factors provides only partial mechanisms for hemostasis. With such considerations, significant interdisciplinary research endeavors have been focused on developing materials and technologies that can be manufactured conveniently, sterilized to minimize contamination and enhance shelf-life, and administered intravenously to mimic, leverage, and amplify physiological hemostatic mechanisms. Here, a comprehensive review regarding the various topical, intracavitary, and intravenous hemostatic technologies in terms of materials, mechanisms, and state-of-art is provided, and challenges and opportunities to help advancement of the field are discussed.

PMID: 29164804 [PubMed - as supplied by publisher]

Real-world experience of afatinib as a first-line therapy for advanced EGFR mutation-positive lung adenocarcinoma.

Oncotarget. 2017 Oct 27;8(52):90430-90443

Authors: Liang SK, Hsieh MS, Lee MR, Keng LT, Ko JC, Shih JY

Abstract
We evaluated the real-world efficacy and side effects of afatinib as a first-line therapy for advanced EGFR mutation-positive lung adenocarcinoma. The medical records of patients receiving afatinib as a first-line therapy after National Health Insurance reimbursement between May 2014 and January 2016 were reviewed, and information on patient characteristics and treatment courses were collected consecutively. Rebiopsy tissue was collected for EGFR mutation and MET amplification analyses. MET amplification was detected by fluorescence in situ hybridization and immunohistochemistry. In total, 140 patients were enrolled (median follow-up, 18.0 months). No significant differences in side effects, treatment responses, progression-free survival, or brain metastasis control were observed between patients receiving 40 mg versus < 40 mg of afatinib during the first 6 months. Patients with significant pretreatment weight loss (> 10.0% in 6 months) had a shorter median progression-free survival. Patients with brain metastases had a poorer Eastern Cooperative Oncology Group performance status and were associated with a shorter median progression-free survival. Nine patients (32.1%) had a p.T790M mutation and only 1 patient gained MET amplifications after disease progression. Afatinib is effective as a first-line therapy for advanced EGFR mutation-positive lung adenocarcinoma. Afatinib dosage does not affect clinical efficacy and drug-related side effects.

PMID: 29163842 [PubMed]

Safety in treatment of hepatocellular carcinoma with immune checkpoint inhibitors as compared to melanoma and non-small cell lung cancer.

J Immunother Cancer. 2017 Nov 21;5(1):93

Authors: Brown ZJ, Heinrich B, Steinberg SM, Yu SJ, Greten TF

Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) is a major health problem worldwide with increasing incidence rates. As HCC traditionally occurs in chronically inflamed livers, this inflammation aids to drive oncogenesis and often renders these lesions to be immunogenic and therefore potential targets for immunotherapy. As patients with HCC generally have underlying liver dysfunction, we sought to determine if immune checkpoint inhibitors were safe to use in patients with HCC as compared to melanoma and non-small cell lung cancer (NSCLC) in terms of the gastrointestinal side effects of elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and diarrhea as well as patients who drop out of the study due to drug toxicity and death secondary to drug toxicity.
METHODS: A literature review was performed for clinical trials that have been completed with single agent immune checkpoint inhibitors for patients with HCC, melanoma, and NSCLC. Gastrointestinal related adverse events including elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and diarrhea were analyzed as well as those patients who were taken off therapy secondary to drug related toxicity and patients who died as a result of therapy.
RESULTS: We found that although patients with HCC treated with immune checkpoint inhibitors have a substantial increase in AST/ALT as compared to patients with melanoma and NSCLC, this does not cause the patients to come off therapy or cause death secondary to drug toxicity.
CONCLUSIONS: We propose immune checkpoint inhibitors are safe to pursue in the treatment of HCC.

PMID: 29157287 [PubMed - in process]

A case of aseptic meningitis in a cetuximab-experienced patient with metastatic colon cancer.

J Oncol Pharm Pract. 2017 Jan 01;:1078155217739685

Authors: Rohrer CL, Grullon Z, George SK, Castillo R, Karasiewicz K

Abstract
Cetuximab is a monoclonal antibody against epidermal growth factor receptor and is used in the treatment of head and neck cancer, non-small cell lung cancer, and colorectal cancer. This case report describes a rare (<1% incidence) side effect of cetuximab administration: aseptic meningitis. We report a case which is, to our knowledge, the only case at the time of submission of this manuscript of aseptic meningitis in a patient being treated for metastatic colon cancer who was not cetuximab-naïve. This case report may help inform clinicians about the identification and outcome of this adverse event.

PMID: 29157147 [PubMed - as supplied by publisher]

Gastroparesis: pharmacotherapy and cardiac risk.

Scand J Gastroenterol. 2017 Nov 20;:1-6

Authors: Hellström PM, Al-Saffar A

Abstract
BACKGROUND: Gastroparesis is characterized by abnormal gastric motility and delayed emptying with symptoms of early satiety, postprandial fullness, bloating, nausea, vomiting and abdominal pain. Pharmacological discovery has been lagging because potential drugs often are associated with abnormalities of electrical conduction of the myocardium due to interaction with cardiac ion channels leading to limited pharmaceutical options for development of new drugs.
OBJECTIVE: Addresses the safety of drugs for gastroparesis in terms of cardiotoxicity related to the clinical use of prokinetics and antiemetics.
METHODS: Survey of QT drugs List and review of current literature.
RESULTS: Many prokinetic drugs are associated with cardiac adverse events and manifest as prolongation of ventricular repolarization, i.e., QT-interval prolongation of the electrocardiogram. This disturbance may develop into a potentially fatal polymorphic ventricular tachyarrhythmia; Torsade de Pointes. Co-administration of prokinetics with other drugs affecting the repolarization process, pharmacokinetic interactions leading to increased blood levels, or the presence of clinical risk factors could further increase the risk for cardiac arrhythmias.
CONCLUSIONS: It is important that clinicians managing gastroparesis are aware of the arrhythmogenic potential of drugs used clinically and risk factors that contribute to QT prolongation to safeguard patients at risk for drug-induced cardiac arrhythmia.

PMID: 29157021 [PubMed - as supplied by publisher]

LMWF-5A for the Treatment of Severe Osteoarthritis of the Knee: Integrated Analysis of Safety and Efficacy.

Orthopedics. 2017 Nov 20;:1-7

Authors: Cole B, McGrath B, Salottolo K, Bar-Or D

Abstract
The low-molecular-weight fraction of 5% human serum albumin (LMWF-5A) is being developed to treat the signs and symptoms of severe osteoarthritis of the knee. This study was a post hoc pooled analysis of 3 randomized placebo-controlled trials of a single intra-articular injection of LMWF-5A, focusing on the subset of patients with severe osteoarthritis of the knee (Kellgren-Lawrence grade 4). Patients were randomized 1:1 to receive a single 4-mL intra-articular knee injection of either LMWF-5A or saline. Safety was assessed as the incidence and severity of adverse events. Efficacy was assessed as the change from baseline to week 12 on the Western Ontario and McMaster Universities Osteoarthritis Index pain (primary outcome), stiffness, and physical function subscores and on patient global assessment scores and was presented as the least squares mean difference and 95% confidence interval. The proportion of responders was defined with the Outcome Measures in Rheumatology-Osteoarthritis Research Society International criteria for scenario D and examined with Pearson's chi-square test. For 417 patients with severe osteoarthritis of the knee, treatment with LMWF-5A resulted in a significant decrease in pain at 12 weeks compared with saline (mean difference, -0.19; 95% confidence interval, -0.34 to -0.04; P=.016), with improvements in function (mean difference, -0.15; 95% confidence interval, -0.31 to 0.01) and patient global assessment (mean difference, -0.30; 95% confidence interval, -0.49 to -0.12) and higher responder rates (64.25% vs 50.90%, P=.006). No drug-related serious adverse events and no deaths occurred, and the incidence and severity of adverse events were similar across treatment groups. This pooled analysis supports the use of LMWF-5A as a safe therapeutic agent for relief of the signs and symptoms of severe osteoarthritis of the knee. [Orthopedics. 201x; xx(x):xx-xx.].

PMID: 29156068 [PubMed - as supplied by publisher]