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Idarucizumab, an agent for dabigatran reversal, is not universally available. Reversal of dabigatran and other novel oral anticoagulants (NOACs) is thus challenging in some clinical settings. A 60-year-old woman with non-ischemic cardiomyopathy and persistent atrial fibrillation on dabigatran

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.

A 58-year-old woman was found to have bilateral ptosis and downward gaze deviation immediately after elective shoulder surgery with general anesthesia and supraclavicular nerve block. A code stroke was activated due to concern for the neurologic process, but neuroimaging did not reveal acute changes or vascular abnormality. Her symptoms gradually resolved in the following hours with supportive care and were ultimately deemed to be related to anesthetic and transdermal scopolamine exposures layered upon her underlying comorbidities. Transient bilateral ophthalmoplegia after general anesthetics has been previously described; drug effect should be considered in the differential of this alarming presentation, which can mimic acute stroke and/or Horner syndrome.

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.

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.

Objective Hypothermia is an adverse drug reaction (ADR) of antipsychotic drug (APD) use. Risk factors for hypothermia in ADP users are unknown. We studied which risk factors for hypothermia can be identified based on case reports.Methods Case reports of hypothermia in APD-users found in PUBMED or EMBASE were searched for risk factors. The WHO international database for Adverse Drug Reactions was searched for reports of hypothermia and APD use.Results The literature search resulted in 32 articles containing 43 case reports. In the WHO database, 480 reports were registered of patients developing hypothermia during the use of APDs which almost equals the number of reports for hyperthermia associated with APD use (n=524). Hypothermia risk seems to be increased in the first days following start or dose increase of APs. APs with strong 5-HT2 antagonism seem to be more involved in hypothermia; 55% of hypothermia reports are for atypical antipsychotics. Schizophrenia was the most prevalent diagnosis in the case reports.Conclusion Especially in admitted patients who are not able to control their own environment or physical status, frequent measurements of body temperature (with a thermometer that can measure low body temperatures) must be performed in order to detect developing hypothermia.

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.

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.

Background Antipsychotic drugs are considered a trigger factor for autonomic dysregulation, which has been shown to predict potentially fatal arrhythmias in schizophrenia. However, the dose-dependent effect of antipsychotic drugs and other psychotropic drugs on autonomic nervous system (ANS) activity remain unclear. The purpose of this study was to investigate the dose-dependent effect of antipsychotic drugs and other clinical factors on ANS activity in an adequate sample size of patients with schizophrenia. Methods A total of 211 Japanese patients with schizophrenia and 44 healthy subjects participated in this study. ANS activity was assessed by means of heart rate variability (HRV) power spectral analysis. Antipsychotic drug treatment and various clinical factors were investigated for each participant. The patient group was categorized into three subgroups according to daily dose of antipsychotic drug, and HRV was compared between groups. Results The results showed significantly decreased low-frequency and high-frequency components of HRV in the patient group compared to the control group. The high-dose group showed a significantly lower HRV than the medium-dose group and an even lower HRV than the low-dose group. In addition, a significant association between HRV and antipsychotic drug dose was identified by multiple regression analysis. HRV was not associated with age, sex, body mass index, duration of illness, or daily dose of other psychotropic drugs. Conclusion These results suggest that antipsychotic drugs exert a significant dose-dependent effect on the extent of decline in ANS activity, and that optimal antipsychotic medication is required to avoid possible cardiovascular adverse events in patients with schizophrenia.