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Background Class 1C antiarrhythmic drugs (AADs) are effective first‐line agents for atrial fibrillation (AF) treatment. However, these agents commonly are avoided in patients with known coronary artery disease (CAD), due to known increased risk in the postmyocardial infarction population. Whether 1C AADs are safe in patients with CAD but without clinical ischemia or infarct is unknown. Reduced coronary flow capacity (CFC) on positron emission tomography (PET) reliably identifies myocardial regions supplied by vessels with CAD causing flow limitation. Objective To assess whether treatment with 1C AADs increases mortality in patients without known CAD but with CFC indicating significantly reduced coronary blood flow. Methods In this pilot study, we compared patients with AF and left ventricular ejection fraction ≥50% who were treated with 1C AADs to age‐matched AF patients without 1C AAD treatment. No patient had clinically evident CAD (ie, reversible perfusion defect, known ≥70% epicardial lesion, percutaneous coronary intervention, coronary artery bypass grafting, or myocardial infarction). All patients had PET‐based quantification of stress myocardial blood flow and CFC. Death was assessed by clinical follow‐up and social security death index search. Results A total of 78 patients with 1C AAD exposure were matched to 78 controls. Over a mean follow‐up of 2.0 years, the groups had similar survival (P = .54). Among patients with CFC indicating the presence of occult CAD (ie, reduced CFC involving ≥50% of myocardium), 1C‐treated patients had survival similar to (P = .44) those not treated with 1C agents. Conclusions In a limited population of AF patients with preserved left ventricle function and PET‐CFC indicating occult CAD, treatment with 1C AADs appears not to increase mortality. A larger study would be required to confidently assess the safety of these drugs in this context.

Levetiracetam (LEV) is a commonly prescribed anti-seizure medication for the prophylaxis and treatment of focal and generalized seizures. However, a few significant LEV-associated adverse effects have been reported in the literature. Here, we describe a case of significant thrombocytopenia within 24 hours of IV LEV administration for generalized seizures in an anticoagulated immunocompetent patient that completely resolved following discontinuation of the medication. Increased awareness of this uncommon thrombocytopenic side effect of LEV especially in the setting of anticoagulation is important for clinicians providing care to patients with a history of seizures due to the heightened risk of clinically significant bleeding.

Bile acids control lipid homeostasis by regulating uptake from food and excretion. Additionally, bile acids are bioactive molecules acting through receptors and modulating various physiological processes. Impaired bile acid homeostasis is associated with several diseases and drug-induced liver injury. Individual bile acids may serve as disease and drug toxicity biomarkers, with a great demand for improved bile acid quantification methods. We developed, optimized, and validated an LC-MS/MS method for quantification of 36 bile acids in serum, plasma, and liver tissue samples. The simultaneous quantification of important free and taurine- and glycine-conjugated bile acids of human and rodent species has been achieved using a simple workflow. The method was applied to a mouse model of statin-induced myotoxicity to assess a possible role of bile acids. Treatment of mice for three weeks with 5, 10, and 25 mg/kg/d simvastatin, causing adverse skeletal muscle effects, did not alter plasma and liver tissue bile acid profiles, indicating that bile acids are not involved in statin-induced myotoxicity. In conclusion, the established LC-MS/MS method enables uncomplicated sample preparation and quantification of key bile acids in serum, plasma, and liver tissue of human and rodent species to facilitate future studies of disease mechanisms and drug-induced liver injury.

CBS deficient individuals undergoing betaine supplementation without sufficient dietary methionine restriction can develop severe hypermethioninemia and brain edema. Brain edema has also been observed in individuals with severe hypermethioninemia without concomitant betaine supplementation. We systematically evaluated reports from 11 published and 4 unpublished patients with CBS deficiency and from additional four cases of encephalopathy in association with elevated methionine. We conclude that, while betaine supplementation does greatly exacerbate methionine accumulation, the primary agent causing brain edema is methionine rather than betaine. Clinical signs of increased intracranial pressure have not been seen in patients with plasma methionine levels below 559 μmol/L but occurred in one patient whose levels did not knowingly exceed 972 μmol/L at the time of manifestation. While levels below 500 μmol/L can be deemed safe it appears that brain edema can develop with plasma methionine levels close to 1000 μmol/L. Patients with CBS deficiency on betaine supplementation need to be regularly monitored for concordance with their dietary plan and for plasma methionine concentrations. Recurrent methionine levels above 500 μmol/L should alert clinicians to check for clinical signs and symptoms of brain edema and review dietary methionine intake. Levels approaching 1000 μmol/L do increase the risk of complications and levels exceeding 1000 μmol/L, despite best dietetic efforts, should be acutely addressed by reducing the prescribed betaine dose.

The incorporation of a clinical pharmacist in daily rounding can help identify and correct errors related to anticoagulation dosing. Inappropriate anticoagulant dosing increases the risk of developing significant bleeding diathesis. Conversely, inappropriate dosing may also fail to produce a therapeutic response. We retrospectively reviewed electronic medical records of 41 patients to confirm and analyze the errors related to various anticoagulants. A clinical pharmacist in an integrated rounding between the period of February 2016 and April 2016 collected this data. We concluded that integrated rounding improves patient safety by recognizing anticoagulant dosage error used for the purpose of prophylaxis or treatment. It also allows us to make dose adjustments based on renal function of the patient. We think that it is prudent for physicians to pay particular attention to creatinine clearance when dosing anticoagulants in order to achieve the intended dosing effect and reduce the risk of adverse drug events.

Background Dronedarone is a benzofuran derivative resembling amiodarone that was intended to reduce the iodine-associated tissue deposition and organ toxicity seen with the latter. The utility of dronedarone for patients with ventricular arrhythmias has not been thoroughly evaluated. We present our experience with its use to treat refractory ventricular tachycardia storm and review the literature. Case presentation An 85 year-old gentleman with multiple medical comorbidities including ischemic and non-ischemic cardiomyopathy with severe biventricular systolic dysfunction presented with ventricular tachycardia storm. Therapeutic options were limited given his frail medical status, failures of sotalol, mexilitine, and catheter ablation therapies along with drug-toxicities from amiodarone. Dronedarone was thus considered as off-label use following informed consent. The patient unfortunately developed fatal multisystem organ failure including acute severe hepatotoxicity from dronedarone. Conclusion Novel therapies for drug-refractory ventricular arrhythmias are long overdue given the limitations of available pharmacologic and non-pharmacologic options. Off-label use of antiarrhythmic agents such as dronedarone is considered a treatment of last-resort in patients who otherwise have no therapeutic options. Given the paucity of reported cases regarding dronedarone for the treatment of ventricular tachyarrhythmias, no conclusive recommendations can be made at this time aside from words of caution. Despite the potential ventricular antiarrhythmic effects of dronedarone, careful patient evaluation is required to identify those at greatest risk of drug-related adverse events particularly in those patients with significant comorbidities such as advanced hepatic, renal, and cardiovascular disease.

ObjectiveTenofovir disoproxil fumarate is a commonly used antiretroviral drug, but risk factors for tenofovir (TFV)-associated kidney disease are not fully understood. We used intensive pharmacokinetic studies in a cohort of HIV-infected women on TFV-based therapy to study the relationship between TFV exposure and subsequent kidney function.DesignThis is a nested study within the Women's Interagency HIV Study, a multicenter, prospective cohort of HIV-infected women. Participants on TFV-based therapy underwent 24-h intensive pharmacokinetic sampling after witnessed dose. Kidney function was measured over the succeeding 7 years by serum creatinine [estimated glomerular filtration rate calculated by serum creatinine (eGFRcr)].MethodsMultivariable linear mixed models evaluated the relationship of baseline TFV area under the-time concentration curves (AUCs) with subsequent changes in kidney function. Covariates included age, diabetes, hypertension, race, BMI, ritonavir use, duration of TFV exposure, current CD4 cell count, and HIV viral load.ResultsOf the 105 participants, persons within the highest baseline TFV AUC tertile had significantly lower eGFRcr compared with those in the lowest tertile (mean ± standard error: 80 ± 4.3 vs. 104 ± 2.5 ml/min per 1.73 m, P

Graphical abstractDisplay Omitted Highlights? Benchmark corpus for adverse effect information extraction from free-text. ? Multiple annotations and thorough harmonization to ensure consistent quality. ? Machine learning-based sentence classification showed reliable outcome. A significant amount of information about drug-related safety issues such as adverse effects are published in medical case reports that can only be explored by human readers due to their unstructured nature. The work presented here aims at generating a systematically annotated corpus that can support the development and validation of methods for the automatic extraction of drug-related adverse effects from medical case reports. The documents are systematically double annotated in various rounds to ensure consistent annotations. The annotated documents are finally harmonized to generate representative consensus annotations. In order to demonstrate an example use case scenario, the corpus was employed to train and validate models for the classification of informative against the non-informative sentences. A Maximum Entropy classifier trained with simple features and evaluated by 10-fold cross-validation resulted in the F1 score of 0.70 indicating a potential useful application of the corpus.

Fosfomycin is a broad spectrum antibiotic, belonging to the group of phosphonic acid antibiotics that is active against most urinary tract pathogens. It is an effective and safe antibi- otic for the treatment of uncomplicated urinary tract infections, which makes it a frequently used drug in our country in this clinical setting. In general, it is well-tolerated and does not appear to cause serious reactions. Most reactions are gastrointestinal. Hepatotoxicity with this drug has been rarely described.We report a case of acute hepatitis induced by a single 3 g dose of fosfomycin, in a previously healthy female adult. © 2010 Sociedade Portuguesa de Gastrenterologia. Published by Elsevier Espana, S.L. All rights reserved.

Nitrofurantoin has well-described associations with a range of adverse pulmonary effects. We report the case of a 72-year old woman with relapsing pneumonitis secondary to the intermittent use of nitrofurantoin, a pattern of disease not well-represented in the literature. The case is also noteworthy as the diagnosis was initially overlooked due to the circumstances of the patient’s medication use. Lung biopsy was avoided by detailed history taking.

The incorporation of a clinical pharmacist in daily rounding can help identify and correct errors related to anticoagulation dosing. Inappropriate anticoagulant dosing increases the risk of developing significant bleeding diathesis. Conversely, inappropriate dosing may also fail to produce a therapeutic response. We retrospectively reviewed electronic medical records of 41 patients to confirm and analyze the errors related to various anticoagulants. A clinical pharmacist in an integrated rounding between the period of February 2016 and April 2016 collected this data. We concluded that integrated rounding improves patient safety by recognizing anticoagulant dosage error used for the purpose of prophylaxis or treatment. It also allows us to make dose adjustments based on renal function of the patient. We think that it is prudent for physicians to pay particular attention to creatinine clearance when dosing anticoagulants in order to achieve the intended dosing effect and reduce the risk of adverse drug events.

In our earlier study, we had reported the case of a patient with rheumatoid arthritis (RA), who had anti-Jo-1 antibodies. This patient had received etanercept (ETN) therapy for RA, after which she had developed overt polymyositis (PM). Although various autoimmune phenomena, including lupus-like diseases, vasculitides, or psoriatic skin lesions, are associated with antitumor necrosis factor (TNF) therapy, the development of PM/dermatomyositis (DM) or antisynthetase syndrome following anti-TNF therapy is extremely rare. Here, we report a case of an RA patient with anti-PL-12 antibodies, who received ETN therapy and subsequently developed the antisynthetase syndrome. She recovered when ETN therapy was withdrawn and high-dose corticosteroid was administered. To date, there have been only five reported cases of RA patients with anti-Jo-1 antibodies who developed overt PM/DM following anti-TNF therapy and only one case of antisynthetase syndrome in an RA patient with anti-PL-7 antibodies. Our patients and the abovementioned reports strongly suggest that onset of overt PM/DM or antisynthetase syndrome in RA patients with anti-aminoacyl tRNA synthetase antibodies is associated with anti-TNF therapy.

The hormone insulin, which is produced in the pancreas, is an important regulator of blood sugar levels. In people with diabetes, the pancreas does not produce sufficient insulin (type 1 diabetes) or the body does not respond appropriately to the insulin (type 2 diabetes). Alcohol consumption by diabetics can worsen blood sugar control in those patients. For example, long-term alcohol use in well-nourished diabetics can result in excessive blood sugar levels. Conversely, long-term alcohol ingestion in diabetics who are not adequately nourished can lead to dangerously low blood sugar levels. Heavy drinking, particularly in diabetics, also can cause the accumulation of certain acids in the blood that may result in severe health consequences. Finally, alcohol consumption can worsen diabetes-related medical complications, such as disturbances in fat metabolism, nerve damage, and eye disease.

Alcohol has numerous adverse effects on the various types of blood cells and their functions. For example, heavy alcohol consumption can cause generalized suppression of blood cell production and the production of structurally abnormal blood cell precursors that cannot mature into functional cells. Alcoholics frequently have defective red blood cells that are destroyed prematurely, possibly resulting in anemia. Alcohol also interferes with the production and function of white blood cells, especially those that defend the body against invading bacteria. Consequently, alcoholics frequently suffer from bacterial infections. Finally, alcohol adversely affects the platelets and other components of the blood-clotting system. Heavy alcohol consumption thus may increase the drinker’s risk of suffering a stroke.

The Ninth Special Report to the U.S. Congress on Alcohol and Health summarizes recent findings from a wide range of alcohol-related research areas. This article provides an overview of the topics covered in the Ninth Special Report and highlights some of the recent findings revealed through the application of innovative research methods.

Therapeutic dose of methylphenidate is known to cause adverse effects (psychosis or mania), albeit in a small number of cases. Signs and symptoms of adverse effects usually disappear on stopping the medicine. Data regarding the safety of methylphenidate in comorbid attention deficit hyperactivity disorder (ADHD) and mental retardation are nonexistent. We describe a case of an 11-year-old girl with ADHD and mental retardation treated with methylphenidate, who developed mania like symptoms requiring inpatient treatment. The index case required psychopharmacological intervention with sodium valproate and olanzapine as the symptoms did not subside even after 3 days. This case highlights the fact that one has to exercise caution while prescribing methylphenidate in patients with comorbid ADHD and mental retardation.

Drug-drug interactions (DDIs) can lead to increased toxicity or reduction in therapeutic efficacy. This study was designed to assess the incidence of potential drug interactions (PDI) and rank their clinical value in post coronary care unit (Post-CCU) of a teaching hospital in Tehran, Iran. In this prospective study, three pharmacists with supervision of a clinical pharmacist actively gathered necessary information for detection of DDIs. Data were tabulated according to the combinations of drugs in treatment chart. Verification of potential drug interactions was carried out using the online Lexi-Interact™ 2011. A total of 203 patients (113 males and 90 females) were enrolled in the study. The mean age of patients was 61 ± 12.55 years (range = 26-93). A total of 90 drugs were prescribed to 203 patients and most prescribed drugs were atorvastatin, clopidogrel and metoprolol. Mean of drugs was 11.22 per patient. A total of 3166 potential drug interactions have been identified by Lexi- Interact™, 149 (4.71%) and 55 (1.73%) of which were categorized as D and X, respectively. The most serious interactions were clopidogrel+omeprazole and metoprolol+salbutamol. Drug interactions leading to serious adverse effects are to be cautiously watched for when multiple drugs are used simultaneously. In settings with multiple drug use attendance of a pharmacist or clinical pharmacist, taking the responsibility for monitoring drug interactions and notifying the physician about potential problems could decrease the harm in patient and increase the patient safety.