Sustained reduction of serum cholesterol in low-dose 6-year simvastatin treatment with minimum side effects in 51,321 Japanese hypercholesterolemic patients.

The Japan Lipid Intervention Trial (J-LIT) study, a nationwide cohort study utilizing the clinical practice of general physicians, was designed to clarify the relationship between the incidence of coronary heart disease and serum lipid concentrations during simvastatin therapy, as well as the safety of the therapy, in a large number of Japanese hypercholesterolemic patients. All the enrolled patients were treated with simvastatin. The current study analyzed the lipid lowering effect and safety of the low-dose simvastatin therapy used in the J-LIT study. Open-labeled simvastatin was given to 51,321 patients at an initial dose of mostly 5 mg/day. After 6 months of the treatment, the average serum total cholesterol (TC) and low density lipoprotein-cholesterol concentrations in all the patients followed up were reduced by 18.3% and 26.0%, respectively, and that of high density lipoprotein-cholesterol increased 2.3% on average. These concentrations were well maintained throughout the 6-year treatment period. A minority of patients (1.4%) unexpectedly had a remarkable reduction in TC concentration by more than 40%. Hyper-responders, even to low-dose statin, were found for the first time in this large-scale and long-term investigation. Overall adverse drug reactions occurred in 3.3% of subjects during the 6-year treatment, the major events being hepatic and musculoskeletal disorders, of which the incidence was less than 1%. Low-dose simvastatin therapy of 5 mg/day effectively controlled the serum TC concentration by reducing it by approximately 20% on average in hypercholesterolemic Japanese patients, a reduction that corresponds to the effect of simvastatin 20 mg/day in Western studies. In addition, the low incidence of drug-related adverse events in this study may be also related to the low dosage of simvastatin.     

Risk factors for heavy burden among family caregivers in a rural town in Hokkaido

OBJECTIVE: The present study was conducted in order to investigate risk factors for heavy burden of family caregivers. STUDY DESIGN: Cross-sectional study. PARTICIPANTS: 51 pairs of the frail elderly and their family caregivers in one town in Hokkaido. RESULTS: Compared to those with a lighter burden, family caregivers with heavier burden looked after the frail elderly with more behavior disturbances due to dementia. They cared for the elderly longer and had less time to go out without accompanying their charges than less burdened caregivers. On the other hand, the elderly had similar activities of daily living and degree of need of care between the two groups. In addition, physical caring time did not differ between the two groups. These findings suggest that the psychological burden may be more important than the physical burden. In addition, caregivers used only 30-40% of services they had the right to use with long-term care insurance. These findings suggest that more convenient services for users should be provided.     

Effect of early mobilization on discharge disposition of mechanically ventilated patients

[Purpose] The purpose of this study was to clarify the benefits of early mobilization for mechanically ventilated patients for their survival to discharge to home from the hospital. [Subjects and Methods] Medical records were retrospectively analyzed of patients who satisfied the following criteria: age ≥ 18 years; performance status 0–2 and independent living at their home before admission; mechanical ventilation for more than 48 h; and survival after mechanical ventilation. Mechanically ventilated patients in the early mobilization (EM) group (n = 48) received mobilization therapy, limb exercise and chest physiotherapy, whereas those in the control group (n = 60) received bed rest alone. Univariate and multivariate logistic regression analyses were performed to identify clinical variables associated with discharge disposition. [Results] Early mobilization was a positive independent factor and the presence of neurological deficits was a negative factor contributing to discharge to home. Among patients surviving mechanical ventilation without neurological deficits, the rate of discharge to home was significantly higher among patients in the EM group that in the control group (76% vs. 40%). [Conclusion] Early mobilization can improve the rate of discharge to home of patients requiring mechanical ventilation because of non-neurological deficits.Key words: Mechanical ventilation, Early mobilization, Physiotherapy     

Two patients treated with pegylated interferon/ribavirin/telaprevir triple therapy for recurrent hepatitis C after living donor liver transplantation

It is difficult to use protease inhibitors in patients with recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) due to interaction with immunosuppressive drugs. We report our experience with two patients treated with telaprevir (TVR) combined with pegylated interferon/ribavirin (PEG IFN/RBV) for recurrent HCV genotype 1 infection after LT. The first was a 63‐year‐old man with HCV‐related liver cirrhosis, who failed to respond to IFN‐β plus RBV after LT. Treatment was switched to PEG IFN‐α‐2b plus RBV and TVR was started. The donor had TT genotype of interleukin (IL)‐28 single nucleotide polymorphisms (SNP) (rs8099917). The recipient had TT genotype of IL‐28 SNP (rs8099917). Completion of 12‐week triple therapy was followed by PEG IFN‐α‐2b plus RBV for 36 weeks. Finally, he had sustained viral response. The second was a 70‐year‐old woman with HCV‐related liver cirrhosis and hepatocellular carcinoma. She failed to respond to PEG IFN‐α‐2b plus RBV after LT, and was subsequently switched to PEG IFN‐α‐2b/RBV/TVR. Genotype analysis showed TG genotype of IL‐28 SNP for the donor, and TT genotype of IL‐28 SNP for the recipient. Serum HCV RNA titer decreased below the detection limit at 5 weeks. However, triple therapy was withdrawn at 11 weeks due to general fatigue, which resulted in HCV RNA rebound 4 weeks later. Both patients were treated with cyclosporin, starting with a small dose to avoid interactions with TVR. TVR is a potentially suitable agent for LT recipients who do not respond to PEG IFN‐α‐2b plus RBV after LT.     

High genomic similarity between European type hepatitis E virus subgenotype 3e strains isolated from an acute hepatitis patient and a wild boar in Mie,Japan

A 67‐year‐old male living in Tsu city, Mie prefecture, Japan was referred to our hospital for further examination of acute liver injury and was diagnosed as having clinical hepatitis E virus (HEV) infection in January 2010. The HEV strain (HE‐JA11‐1701) isolated from the patient belonged to genotype 3 and European‐type subgenotype 3e. It was presumed that the patient had been infected from a wild boar (Sus scrofa leucomystax) because he consumed meat/viscera from a wild boar that he had captured himself as a hunter approximately 2 months before disease onset. A specimen of the boar meat/viscera that the patient had ingested was not available. However, the HE‐JA11‐1701 strain was 99.8% identical within the 412‐nucleotide sequence of the open reading frame 2 region to a HEV strain (JBOAR012‐Mie08) that had been recovered from a wild boar captured near the patient's hunting area in 2008. A phylogenetic analysis confirmed that the two HEV strains had a close genetic relationship and were segregated into subgenotype 3e, supported by a high bootstrap value of 99%. Of note, the HE‐JA11‐1701 and JBOAR012‐Mie08 strains were remotely related to the 3e strains reported in Japan and European countries, with a nucleotide difference of 7.9–13.9%, reinforcing the uniqueness of the 3e strains obtained in the present study. These results strongly support our speculation that the patient developed acute hepatitis E via consumption of HEV‐infected boar meat/viscera. Genetic analyses of HEV strains are useful for tracing infectious sources in sporadic cases of acute hepatitis E.     

Drinking frequency modifies an association between salt intake and blood pressure: A cohort study

Salt sensitivity is one of the crucial risk factors of hypertension. The aim of the present prospective cohort study was to assess the clinical impact of alcohol drinking on an association between salt intake and blood pressure. The present study included 451 employees at a pharmaceutical company in Japan who underwent annual health checkups in both 2017 and 2018. The main exposure of interest was self‐reported drinking frequency at their first checkups: rarely, occasionally, and daily. To assess the association between the change of salt intake estimated from single‐spot urine specimens and that of blood pressure, the differences in systolic/diastolic blood pressure and salt intake between 2017 and 2018 were calculated for each subject. Multivariable‐adjusted linear regression models adjusting for clinically relevant factors clarified a drinking frequency‐dependent association between Δsalt intake and Δsystolic blood pressure (per 1 g/d of Δsalt intake adjusted β [95% confidence interval] 0.19 [−0.73, 1.12], 0.84 [0.14, 1.53], and 1.78 [0.86, 2.69] in rare, occasional, and daily drinkers). A similar association between Δsalt intake and Δdiastolic blood pressure was also observed (−0.24 [−1.02, 0.54], 0.67 (0.18, 1.16), 0.95 [0.38, 1.51], in rare, occasional, and daily drinkers). The interactions between drinking frequency and Δsalt intake were found to be statistically significant (P for interaction = .028 and .006 for ∆systolic blood pressure and ∆diastolic blood pressure, respectively). The present study identified enhanced salt sensitivity in the subjects who drink at a higher frequency, suggesting that the reduction in alcohol consumption may improve salt sensitivity in higher frequency drinkers.