Background: Acetaminophen is widely used as an analgesic and antipyretic; however, acetaminophen overdose is known to cause hepatic injury. However, minor and self-limiting alanine aminotransferase (ALT) elevation unrelated to hepatic injury is occasionally observed in individuals receiving high-dose acetaminophen. The aim of this study was to evaluate the changes in liver function markers induced by long-term, high-dose acetaminophen administration.

Methods: Acetaminophen (3000 mg/day) or placebo was repeatedly administered to 242 healthy Japanese adults for 28 days. Plasma samples collected on Day 1 were used to measure the pharmacokinetics of acetaminophen. Liver function was monitored in terms of aspartate aminotransferase (AST), ALT, alkaline phosphatase (ALP), total bilirubin (T-Bil) , and high mobility group box 1 (HMGB-1) levels for 35 days, from the day of the first dose. Subjects were withdrawn from the study if their AST, ALT, or ALP levels exceeded twice the respective upper limit of normal (2×ULN).

Results: From a total of 242 subjects, 202 and 40 subjects were assigned to the acetaminophen group and the placebo group, respectively. Twelve subjects in the acetaminophen group (6.0％) were withdrawn owing to ALT elevation over 2× ULN; no subjects were withdrawn from the placebo group. During the study period, ALT was higher in the acetaminophen group than in the placebo group, and increased from Day 7 to 14 after the start of administration. However, no evidence of hepatic injury owing to acetaminophen was observed, and the ALT elevation was attenuated after Day 14. Moreover, no correlation was observed between maximum ALT and levels of HMGB-1, a novel biomarker candidate for hepatic injury, during the study period. These findings led us to conclude that the ALT elevation was not caused by hepatic injury.

Conclusion: ALT elevation >2×ULN was observed in 6.0％ of subjects in the acetaminophen group. However, no subjects developed hepatic injury, and ALT levels started to return to the normal values even during continued administration. The phenomenon of adaptation may be involved in these changes.

Background: Arrhythmias are common in patients with coronary artery disease and heart failure (HF), and confer substantial risks of mortality and morbidity. Amiodarone is an antiarrhythmic drug with potential benefits in HF. The aim of this study was to evaluate the prognosis and change in systolic function of Japanese patients with severe ischemic HF and arrhythmia prescribed amiodarone.

Methods: This single-center, single-arm, retrospective study included 68 patients with ischemic HF 〔New York Heart Association (NYHA) functional class III or IV〕 and left ventricular ejection fraction (LVEF) ≤ 35% who were prescribed amiodarone between 1995 and 2010. The median follow-up period was 25 months. The primary endpoint was death from any cause. The secondary endpoints were cardiovascular death, hospitalization due to worsening HF, and ventricular tachyarrhythmias. Echocardiographic parameters were evaluated during the first 2 years after initiation of therapy.

Results: The cumulative rate of death from any cause was 39% and 62% at 2 years and 5 years, respectively. The cumulative rates of cardiovascular death, hospitalization due to worsening HF and ventricular tachyarrhythmia was 44%, 58% and 29% at 5 years, respectively. Echocardiographic findings showed no changes in left ventricular dimension/volume or LVEF during 2 years of amiodarone therapy. Amiodarone therapy was discontinued in 10 patients (15%) because of its pulmonary toxicity or other adverse effects.

Conclusion: The prognosis of patients with severe ischemic HF and reduced LVEF who received amiodarone was limited and their systolic function was not improved.

Parkinson's disease (PD) causes motor impairment, but motor dysfunction can be improved by treatment. However, the package inserts of PD therapeutic drugs state “do not drive a car” as an important precaution in Japan. In addition, the package insert of non-ergot dopamine agonist (DA) states specifically “do not drive a car or operate a machine” as a warning because non-ergot DA causes sudden sleepiness and somnolence. On the other hand, driving is a very important means of transportation for daily living and work. Even though doctors explain at the clinic that the patients should not drive while on medications, many patients are forced to drive in everyday life. In addition, somnolence and sudden sleepiness differ among individuals. Therefore, doctors are confused about instructing patients to refrain from driving. We investigated the relation between non-ergot DA and driving situation in PD patients, which is a serious issue in the clinical setting. All 362 PD patients who visited our offices were interviewed regarding their driving situation, and detailed medications and car accidents were examine in 154 patients who continued driving a car or stopped driving after the onset of disease. In the investigation of medications, 51 patients were taking non-ergot DA, 36 patients (70.6%) of whom continued to drive. In addition, 20 of 154 patients had serious car accidents, but only six of the accidents were associated with somnolence and sudden sleepiness. In the examination of medications at the time of accident, there was no difference between non-ergot DA and other medications. These results suggest that upon receiving instructions from healthcare professionals, PD patients drive while making appropriate judgment about medication-induced somnolence. However, in this study, the number of patients who experienced serious car accidents was small, and the numbers of patients taking ergot DA and non-ergot DA were limited. Further larger scale study is required to confirm the findings. Preparation of guidelines related to instructions on taking PD medications is necessary, which include medication taking during holidays, consideration of the occurrence of sudden sleepiness and somnolence, and judgement of whether to continue driving.

Background: Although pill counts can objectively measure medication adherence, they are often labor-intensive and time-consuming, especially in patients taking numerous medications. We hypothesized that counting pills for not all but only some medications, which would undoubtedly spare time and labor, could provide reliable information on adherence to all medications. The aim of the present study was to evaluate how accurately medication adherence could be assessed using partial pill counts.

Methods: We retrospectively analyzed pill count data from 158 consecutive Japanese type 2 diabetic outpatients treated with polypharmacy. Adherence was defined as an 80% or higher medication consumption rate, whereas non-adherence was defined as <80%. We assessed how accurately a patient's adherence to one medication could be predicted based on information on his/her adherence to another medication.

Results: The positive likelihood ratio for adherence (i.e.,reciprocal of the negative likelihood ratio of non-adherence) was 2.4 (95% confidence interval: 1.7 to 3.3) , whereas that for non-adherence (i.e., reciprocal of the negative likelihood ratio of adherence) was 9.9 (95% confidence interval: 7.1 to 13.8) (both p<0.05). The accuracy was dependent on the consistency of administration times. Adherence (or non-adherence) to a medication could be more accurately predicted based on information regarding another medication with the same administration schedule, compared with another with a different administration schedule.

Conclusion: Adherence (or non-adherence) to medications could be predicted with considerable accuracy based on information regarding adherence (or non-adherence) to another medication in type 2 diabetic patients treated with polypharmacy.