Objective：The objective of this study was to apply Least Absolute Shrinkage and Selection Operator （LASSO）logistic regression to detection of adverse drug reaction （ADR） signals using an electronic health records database as a comprehensive and quantitative method to supplement the current pharmacovigilance activities in Japan.

Design：case-control study

Methods：We analyzed data from 40767 inpatients using a single-institution hospital database and identified two ADRs, suspected pancreatitis and thrombocytopenia, using abnormal laboratory test results. LASSO logistic regression analysis was applied to detect ADR signals with adjustment for age, sex, comorbidities and medical procedures. The positive predictive value （PPV） was calculated using reference standard of known drug-ADR associations based on drug product labels.

Results：The number of case group was 6735 for suspected pancreatitis and 11561 for thrombocytopenia. The number of ADR signals detected using LASSO logistic regression was 27 for suspected pancreatitis and 40 for thrombocytopenia. The calculated PPV was 3.7% for suspected pancreatitis and 55.0% for thrombocytopenia.

Conclusion：LASSO logistic regression analysis efficiently detects ADR signals by adjusting for confounding factors such as comorbidities and medical procedures. The false positive signals may contain unknown signals and further signal assessment will be needed.

The effects of high concentration mineral water bating (31.16g/kg, mainly composed of Na, Ca, Mg chloride and sulfate) were studied in 13 healthy men (44.9±16.3y.o.). The subjects took 41°C, 10min bathing and kept warmth by a blanket for 30min. Blood pressure (BP), Heart rate (HR), cardiac output (CO), total peripheral resistance (TPR) and sublingual temperature by electric thermista as deep body temperature were measured during and after bathing. Skin blood flow by LASER doppler flow meter and venous partial gas pressure and pH were also measured.
Sublingual and forehead temperature was increased significantly by +1.4°C after 10min bathing and +0.9°C increase continued even after 30min. Diastolic BP and TPR were significantly decreased, and HR and CO were significantly increased by +20bpm and +2.7l/min, respectively. Significant increase of skin blood flow was also demonstrated. Significant increase of venous pO₂ (+20 Torr) and decrease of pCO₂ (-8.0 Torr) suggested the improvement of peripheral oxidative metabolism due to increased CO.
High concentration mineral water bathing was highly effective than simple water bathing probably due to the thick coating effect by binding concentrated minerals with skin furface protein.

It is generally accepted that secretory immunoglobulin A (sIgA) is a major effector of local immunity in the oral cavity. The salivary sIgA level is known to be temporarily decreased after an acute single bout of intense exercise. On the other hand, the effect of continuous exercise training on salivary sIgA has been controversial. In the present study, we collected timed saliva samples from collegiate kendoists using the reliable saliva collection method that has already been reported. The collection was performed before, during and after a traditional high-intensity 10-day training camp during the coldest part of the winter. We investigated the effect of repetitious intense exercise training on resting sIgA levels in saliva.
The subjects were 19 males and 8 females (age: 19.9±0.5 years) who took part in the camp. We obtained saliva samples before the camp, on the first and the 10th days of the camp, and 4 and 10 days after the camp at 5 p. m. The concentration of sIgA was measured by ELISA, and the sIgA secretion rate was calculated.
The resting sIgA secretion rate decreased significantly during the camp. It remained at a lower level 4 and 10 days after the camp compared to the initial level, although it tended to recover gradually. Prolonged suppression of the resting sIgA secretion rate during a traditional winter kendo training camp might be induced by repetition of high-intensity training.

Side to side difference in tennis players' mid-radius and cross-sectional study on mid-tibia of jumpers and sedentary controls suggest that the improvement of mechanical properties of cortical bone in response to long-term exercise is related to geometric adaptation and not to volumetric bone mineral density. In the present study, geometric and mechanical properties of right tibia were estimated along 64 directions centering center of gravity of the bone on cross-sectional peripheral quantitative computed tomography (pQCT) images. The tibias of 17 jumpers (7 females, 10 males) and 15 controls (8 females, 7males), aged 18-23, were scanned at mid site using pQCT. Periosteal and endocortical radius were larger, cortical thickness was thicker, and mechanical properties (moment of inertia of area and strength strain index) were greater in jumpers compared to those of controls. The differences in cortical thickness between the two groups were dependent on direction of measurement. Defined a direction from tibia's center of gravity to fibula's as 0°, difference in the cortical thickness between jumpers and controls was the greatest at around 240°. Along this direction, differences in mechanical properties were also the most significant, suggesting that the site-specific adaptation of bone to long-term exercise is due to geographical relation of bone to muscle.

Objective: We conducted a questionnaire survey to comprehend the situation regarding the collection, provision, and utilization of drug safety information at hospitals.  In addition, we asked pharmaceutical companies how they select medical institutions to provide drug safety information.  We also investigated the current situation of information provision to Tokyo Medial Center by pharmaceutical companies.
Method: A questionnaire was mailed to all hospitals in Japan.  The survey was conducted between January 13 and February 10, 2011.  Moreover, we asked thirteen pharmaceutical companies by telephone and e-mail about the implementation status of the provision of information and performed a survey at Tokyo Medical Center on the current situation of information provision by pharmaceutical companies regarding revisions to precaution sections in package inserts.
Results: The results of the questionnaire survey (response rate: 41.2%) showed that the major information sources for hospitals were medical representatives (77.8%), Drug Safety Update (50.3%) and direct mails (49.3%).  Furthermore, in the case of drugs prescribed exclusively for extramural dispensing, fewer hospitals responded that medical representatives of the pharmaceutical companies provided drug safety information and more hospitals responded that they did not obtain any drug safety information at all, compared with drugs listed in the hospital formularies.
Conclusion: To minimize the risks of drugs, healthcare professionals must collect a wide range of drug safety information and must utilize this information in their medical practice.  Therefore, it is important that pharmaceutical companies and regulatory authorities make an effort to provide suitable information dissemination to medical institutions.  Furthermore, medical institutions must also strengthen their systems for collecting drug safety information and providing such information to healthcare professionals.

Medical students at Kurume University begin practical training in clinical skills in their fourth year. At that time, students use the skills laboratory to improve their clinical skills. Medical education resources in the skills laboratory include simulators for emergency resuscitation and heart diseases, wireless stethoscopes, and videotapes. All students use the skills laboratory for 2 months, and its usefulness was evaluated with questionnaires after practical training. More than 50 % of students approved of their practice in the skills laboratory. However, some students were unsatisfied because they were unable to make effective use of the simulators. In the future, an improved skills laboratory will be necessary to improve practical training in the clinical skills for medical students.

We analyzed the scores of objective structured clinical examinations (OSCEs) and written examinations administered to fourth-year medical students after practical training in clinical skills and to fifth-year medical students after clinical training and scores of graduation examinations taken by sixth-year medical students. Correlations were analyzed among the scores of 96 students who had taken all 3 examinations during a 3-year period. Mean scores on examinations in the fourth, fifth, and sixth years were compared between sixth-year students who did or did not graduate and between graduating students who did or did not pass the national examination for medical practitioners in Japan. Significant correlations in the scores were found between 1) OSCEs and written examinations for fourth-year students versus those for the fifth-year students; 2) OSCE and written examinations for fourth-year students versus graduation examination scores for the sixth-year students; and 3) OSCE and written examinations for fifth-year students versus graduation examination scores for sixth-year students. In addition, the mean scores in the fourth and fifth years were significantly higher for sixth-year students who graduated and passed the national examination than for students who did not graduate or who graduated but failed the national examination. These results suggest that the practical training in clinical skills given to fourth-year students and the clinical training given to fifth-year students strongly affect the overall evaluation of the ability of sixth-year students and success on the national examination.

Objective To assess the effect of D-JNKI1, an inhibitor of c-Jun N-terminal kinase (JNK), on delayed neuronal death (DND) in a gerbil model of transient global cerebral ischemia, so as to further study the roles of JNK activation in mediating neuronal cell death in brain ischemia. Methods Fifty-five Mongolian gerbils were randomly divided into 11 groups. Animals (n=35) assigned into 7 groups (n=5 per group) were subjected to 5-min occlusion of bilateral common carotid arteries (BCCAO);among the 7 groups, different doses of D-JNKI1 (0.00012, 0.0012, 0.012, 0.12, 1.2 μmol/L in 2 μL PBS,n=5 each) were administered stereotaxically into right lateral ventricles 3 h after reperfusion; the control group (n=5) received 2 μL PBS; and another group (n=5) received 1.2 μmol/L of D-JNKI1 in 0.5 mL PBS intraperitoneally. Sham-operated animals (n=5) only received the exposure of bilateral common carotid arteries without occlusion. Three groups (n=5 in each) were pretreated with D-JNKI1 (0.00012,0.0012 μmol/L in 2 μL PBS) or only 2 μL PBS 30 min before 2-min BCCAO, and subjected to 5-min BCCAO 48 h after the first ischemic insult. All animals were sacrificed 4 d after 5-min BCCAO and prepared for frozen section and Nissl staining. Results The treatment with D-JNKI 3 h after 5-min ischemia was neuroprotective with a maximum effect at a dose of 0.0012 μmol/L. Pretreatment with D-JNKI augmented ischemic tolerance induced by 2-min ischemia. Conclusion D-JNKI1 has a potential neuroprotective effect on DND in CA1 of hippocampus in gerbils with global cerebral ischemia-reperfusion injury.

Objective：The objective of this study was to apply Least Absolute Shrinkage and Selection Operator （LASSO）logistic regression to detection of adverse drug reaction （ADR） signals using an electronic health records database as a comprehensive and quantitative method to supplement the current pharmacovigilance activities in Japan.Design：case-control studyMethods：We analyzed data from 40767 inpatients using a single-institution hospital database and identified two ADRs, suspected pancreatitis and thrombocytopenia, using abnormal laboratory test results. LASSO logistic regression analysis was applied to detect ADR signals with adjustment for age, sex, comorbidities and medical procedures. The positive predictive value （PPV） was calculated using reference standard of known drug-ADR associations based on drug product labels.Results：The number of case group was 6735 for suspected pancreatitis and 11561 for thrombocytopenia. The number of ADR signals detected using LASSO logistic regression was 27 for suspected pancreatitis and 40 for thrombocytopenia. The calculated PPV was 3.7% for suspected pancreatitis and 55.0% for thrombocytopenia.Conclusion：LASSO logistic regression analysis efficiently detects ADR signals by adjusting for confounding factors such as comorbidities and medical procedures. The false positive signals may contain unknown signals and further signal assessment will be needed.

BACKGROUND: An increase in cardiovascular diseases has been reported following major disasters. Previous work has shown that ultrasonographic findings from ultrasound cardiography examination (UCG) increased until the 44th month after the tsunami caused by the Great East Japan Earthquake. The present study conducted UCG among victims in the tsunami disaster area and investigated the frequency of disaster-related cardiovascular diseases and changes over time until the 55th month after the disaster. METHODS: The subjects were residents of temporary housing complexes and neighboring housing in Watari-gun, Miyagi Prefecture, Japan. There were 207 subjects in the 18th month, 125 in the 30th month, 121 in the 44th month, and 106 in the 55th month after the disaster. Data were collected through UCG and self-report questionnaire. RESULTS: Significant changes were observed among subjects with clinical findings from the UCG, which increased over the study period-from 42.0 to 60.8, 72.7, and 73.6% beginning in the 18th month after the disaster (p < 0.0001). CONCLUSIONS: It is possible that the UCG can become a useful examination to visualize the potential impact of a major disaster on the cardiac function of victims. Victims with clinical findings continued increasing not only during the acute phase after a disaster but also in the long term. We therefore need to keep this in mind, and note that it is important to establish a support system to control cardiovascular diseases from the early stage of disaster. TRIAL REGISTRATION UMIN; ID000029802. R000034050 . 2 November 2017.
Aged ; Aged, 80 and over ; Cardiovascular Diseases ; diagnosis ; diagnostic imaging ; Case-Control Studies ; Disasters ; statistics & numerical data ; Earthquakes ; Female ; Health Behavior ; Humans ; Japan ; Male ; Middle Aged ; Tsunamis