Risk of Lactic Acidosis in Hospitalized Diabetic Patients Prescribed Biguanides in Japan: A Retrospective Total-Population Cohort Study.

Patient data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) are used to assess the effect of biguanide administration on rates of lactic acidosis (LA) in hospitalized diabetes mellitus (DM) patients. In this retrospective cohort study (from April 2013 to March 2016), we compare DM inpatients prescribed biguanides to DM inpatients who were not prescribed biguanides to quantify the association between biguanides and incidence of LA. In total, 8,111,848 DM patient records are retrieved from the NDB. Of the 528,768 inpatients prescribed biguanides, 782 develop LA. Of the 1,967,982 inpatients not prescribed biguanides, 1310 develop LA. The rate ratio of inpatients who develop LA and are administered biguanides to those who developed LA without receiving biguanides is 1.44 (95% CI, 1.32-1.58). Incidence rates and rate ratios for both sexes are elevated in the group prescribed biguanides for patients aged 70 years and older, markedly in those 80 years and older: 40.12 and 6.31 (95% CI, 4.75-8.39), respectively, for men and 34.96 and 5.40 (95% CI, 3.91-7.46), respectively, for women. Biguanides should be used conservatively in patients older than 70 years, particularly for those with comorbidities, and with caution in patients 80 years and older.

Basic biology education in high school and acceptance of genetically modified food in Japan.

While many types of genetically modified (GM) food have become more available worldwide, the acceptance of GM food continues to be low. To increase this acceptance, various educational interventions have been conducted; however, conflicts remain about the safety and acceptability of GM food among laypeople, experts, and policymakers in several countries. Thus, this study aimed to clarify whether basic biology education influences Japanese people's acceptance of GM food. We examined this idea by comparing individual experiences of high school biology education based on curriculum and proficiency level. We distributed online questionnaires to 1,594 people in Japan; 1,122 valid responses (70.4%) were obtained. Results showed that the acceptance rates of GM vegetables, fish, and meat were 33.6%, 29.0%, and 29.1%, respectively. Comparing the biology knowledge test scores according to different high school biology education levels (i.e., non-learners, basic, and advanced levels) showed no significant differences between the three age groups (20s, 30s, and 40s), which corresponded to different curricula (p = 0.90); however, there were significant differences between the high school biology education levels (p<0.01). Using logistic regression analysis, we then examined the effect of high school biology education on acceptance of GM food. The results showed no significant differences between different high school biology education levels but significantly lower acceptance by the 30s and 40s groups compared with the 20s group (p<0.05). This suggests that basic biology education alone is not sufficient to change people's attitudes toward GM foods. These generational differences suggest factors other than high school biology curriculum affect different generations' acceptance of GM foods. Overall, high school biology education did not directly affect acceptance of GM foods, although those who received a higher level of education had an increased knowledge of GM foods.

Evaluation of Japanese people's perception of risk information for making decisions to receive influenza and rubella vaccinations.

BACKGROUND: Generally, vaccination uptake in Japan lags behind World Health Organization targets. OBJECTIVE: This study aimed to understand how risk information and advice affect intention to receive vaccinations. METHODS: This study had a within-subjects design. An online survey based on the Health Belief Model was sent to 2501 Japanese individuals (≧20 years) to assess the intention to be vaccinated for influenza and rubella after receiving minor and severe risk information and hypothetical advice about each vaccine. Regression analysis was used to measure changes in intentions to receive each vaccination after being provided with (1) risk information about each vaccine and (2) hypothetical encouragement and discouragement to be vaccinated. MAIN OUTCOMES: The main outcomes included changes in vaccination intentions from baseline. RESULTS: Forty-one percent (N = 1030) of those sent the survey completed it. At baseline, 43% and 65% of the respondents intended to have influenza and rubella vaccinations, respectively. Being provided with information about severe risks and susceptibility increased the intention to have the influenza vaccination among females in their 40s. Receiving inaccurate and discouraging information from one's mother significantly decreased the intention to have the rubella vaccination. Women 50 and older were more likely to intend not to have vaccination for rubella. Severe risk information decreased rubella vaccination intention in all age groups, except women in their 30s and 40s (p < .05). CONCLUSION: For both vaccinations, older individuals demonstrated vaccine hesitancy. This group requires tailored messaging to help them understand their vulnerability (to influenza) and their role in transmission (for rubella) to encourage uptake of essential vaccinations. PATIENT OR PUBLIC CONTRIBUTION: Members of the Japanese public responded to our online questionnaire on vaccination risk.

Comparison between tools for measuring breathlessness: Cross-sectional validation of the Japanese version of the Dyspnoea-12.

INTRODUCTION: The Dyspnoea-12 (D-12) is a brief, easy to complete questionnaire for measuring breathlessness. OBJECTIVES: To facilitate further efforts to measure dyspnoea in real clinical settings, the authors aimed to develop and validate a Japanese version of the D-12 and also compare the D-12 with the Baseline Dyspnea Index (BDI) and the Activity component of the St. George's Respiratory Questionnaire (SGRQ). METHODS: The standardized procedure in accordance with international guidelines was used to create the translation. A validation study with a cross-sectional observational design was conducted on 122 subjects with stable chronic obstructive pulmonary disease (COPD). RESULTS: The internal consistency of the D-12 was high (Cronbach's coefficient α = 0.883) and similar to that of the BDI (α = 0.824) and SGRQ Activity (α = 0.872). The relationships between tools were statistically significant (|Rs | = 0.53 to 0.66). Although the scores obtained from all three tools were skewed toward the milder end of the respective scales, this deviation was most prominent in the D-12 with a floor effect of 48.4%. CONCLUSION: The Japanese version of the D-12 was successfully validated, but we should be careful of any floor effect and marked skew to the mild end of the scale, especially in subjects with mild COPD.

Current Status of Clinical Engineer Anesthesia Assistants and Their Effect on Labor Task Shifting in Japan: A Prospective Observational Study in a Single Institute.

INTRODUCTION: Anesthesiologists are in short supply across the world, resulting in perpetually long working hours. To reduce the burden on anesthesiologists, tasks that can be performed by non-physicians must be shifted to other medical staff. In hospitals, clinical engineers can work as anesthesia assistants and perform some of the duties of anesthesiologists. This study aimed to evaluate the effect of task shift performed by clinical engineer anesthesia assistants (CEAAs). METHODS: This was a 1-month prospective observational study that included 33 anesthesiologists (11 fellows and 22 certified anesthesiologists) and 11 CEAAs. The total activity and anesthesia times were extracted from the attendance record as indices of the anesthesiologists' work status. The CEAAs recorded the duration of work performed on behalf of the anesthesiologists as task shift time. The task shift rate was evaluated as follows: task shift time/(task shift time + total activity time) and task shift time/(task shift time) + (total anesthesia time). RESULTS: The study period consisted of 19 weekdays. The average daily activity time of the anesthesiologists was 10.1 h, and the average anesthesia time was 8.5 h. The CEAAs performed a total of 546.8 h of task shift. The defined task shift rate was 20.1% when the total activity time was the denominator and 23.1% when the anesthesia time was the denominator. CONCLUSIONS: CEAAs might be effective in reducing the working hours of anesthesiologists through task shift. Their taking over a portion of the anesthesiologists' duties may allow the anesthesiologists to work more efficiently.

Coronary artery aneurysm complicated by pneumothorax with a history of Kawasaki disease.

Kawasaki disease (KD) is a common vasculitis disorder of childhood. It can sometimes complicate coronary artery aneurysms, and treatment is required depending on the condition of stenosis. A 20-year-old man was referred for surgery with a coronary artery aneurysm and stenosis in the left coronary artery as sequelae of KD. He had a surgical history of left pneumothorax and bullae remaining on the right lung. We simultaneously performed off-pump coronary artery bypass for coronary artery stenosis and bullectomy. Coronary artery aneurysms with KD complicated by pneumothorax are rare, and we treated them using one-stage surgery.

Dramatic response to nivolumab after local radiotherapy in pulmonary pleomorphic carcinoma with rapid progressive post-surgical recurrence.

Pulmonary pleomorphic carcinoma (PPC) is resistant to anticancer drug treatment, outcomes are poor, and no standard therapy has been established. High PD-L1 expression has been found in PPCs, suggesting the possible efficacy of an immune checkpoint inhibitor (ICI) in cancer immunotherapy; however, this approach requires further investigation through case accumulation. Herein, we report a case of rapid recurrence and progression of PPC early after surgery in a 70-year-old male ex-smoker. Surgery was performed for lung cancer of the right lower lobe, and a pathological examination indicated primary PPC with high PD-L1 expression (tumor proportion score: 90%). Because systemic metastasis recurred only six weeks after surgery, nivolumab was administered as second-line treatment. Marked tumor regression was observed on imaging after three cycles, revealing a near complete response. Palliative radiotherapy was applied to the bone metastasis region for pain relief before nivolumab was administered. This case suggests that an ICI can have an effect on PPC and that the efficacy of ICIs may be enhanced by radiotherapy-induced abscopal effects.

Regulation of secretion and enzymatic activity of lipoprotein lipase by C-mannosylation.

Lipoprotein lipase (LPL) is a crucial enzyme in lipid metabolism and transport, and its enzymatic deficiency causes metabolic disorders, such as hypertriglyceridemia. LPL has one predicted C-mannosylation site at Trp417. In this study, we demonstrated that LPL is C-mannosylated at Trp417 by mass spectrometry. Furthermore, by using wild-type and a C-mannosylation-defective mutant of LPL-overexpressing cell lines, we revealed that both secretion efficiency and enzymatic activity of C-mannosylation-defective mutant LPL were lower than those of wild-type. These data suggest the importance of C-mannosylation for LPL functions.

Japanese Consumer Perceptions of Genetically Modified Food: Findings From an International Comparative Study.

BACKGROUND: Reports of food-related incidents, such as cows infected with bovine spongiform encephalopathy (2001) and the Fukushima nuclear accident (2011), engendered significant fear among Japanese consumers and led to multiple farmer suicides, even when no actual health damage occurred. The growing availability of genetically modified (GM) food is occurring against this backdrop of concern about food safety. Consumers need information to assess risk and make informed purchasing decisions. However, we lack a clear picture of Japanese consumer perceptions of GM food. OBJECTIVE: This study aims to understand Japanese consumer perceptions of GM food for risk communication. Consumer perceptions of GM food were compared among 4 nations. METHODS: A Web-based survey was conducted in Japan, the United States, the United Kingdom, and France. Participants were asked about demographics, fear of health hazards, resistance to GM and breeding-improved products, perception of GM technology and products, and willingness to pay. Multiple linear regression analyses were conducted, as were t tests on dichotomous variables, and 1-way analysis of variance and post hoc tests. RESULTS: Of 1812 individuals who agreed to participate, 1705 (94%) responded: 457 from Japan and 416 each from France, the United States, and the United Kingdom. The male/female and age group ratios were all about even. Some resistance to GM food was seen in all countries in this study. France showed the strongest resistance (P<.001), followed by Japan, which had stronger resistance than the United States and the United Kingdom (P<.001). Overall, females, people in their 60s and older, and those without higher education showed the greatest resistance to GM food. Japan showed stronger fear of food hazards than other nations (P<.001, odds ratio=2.408, CI: 1.614-3.594); Japanese and French respondents showed the strongest fear of hazards from GM food (P<.001). Regarding perceptions of GM technology and products, consumers in nations other than Japan would accept GM food if it were appropriately explained, they were provided with scientific data supporting its safety, and they understood that all food carries some risk. However, Japanese consumers tended to accept GM technology but rejected its application to food (P<.001). Of those willing to purchase GM food, consumers in Japan required a discount of 30% compared with about 20% in other nations. CONCLUSION: All consumers in our study showed resistance to GM food. Although no health hazards are known, respondents in Japan and France strongly recognized GM food as a health risk. Price discounts of 30% and GM technology may be communication cues to start discussions about GM food among Japanese consumers. Although education-only risk communication generally is not effective, such an approach may work in Japan to help consumers better understand GM technology and, eventually, GM food. The gap between accepting GM technology and rejecting its application to food should be explored further.

Values and risks of second opinion in Japan's universal health-care system.

BACKGROUND: Second opinion (SO) is widely recognized in Japan, but we do not know how patients view and use SO. OBJECTIVES: To investigate optimum seeking of SO in Japan's universal health-care system. DESIGN, PARTICIPANTS, AND METHODS: Survey of patients at Tokyo Medical and Dental University Hospital. Of 365 responses, 67 had experienced SO with standardized protocol at SO Clinic; 82 had obtained SO elsewhere without instruction; 216 had never sought SO. MAIN OUTCOME MEASURES: Views of values and risks of SO. RESULTS: Second opinion patients with standardized protocol better understood their illness, treatment options, individualized plan, and uncertainty in medicine, and also reported improved decision making compared with SO patients without the protocol (P < 0.05). However, more than half of respondents misunderstood SO as a way to change doctors or treatment. Second opinion respondents (n = 149) had a propensity to request treatment changes (P < 0.1) and more than one-third (n = 82) did not tell SO doctor they were being treated by another doctor. The absolute majority of non-SO patients would seek SO for a serious illness but would hesitate to tell their doctors. DISCUSSION AND CONCLUSION: Respondents recognized value of SO to improve understanding and decision making. This study also found risks in SO misuse which may be reinforced by Japan's cultural tendencies and universal health-care system. Our findings suggest steps to increase the benefit of SO: ensure involvement of original doctor, instruct patients about SO and help them organize their thinking before SO and facilitate patients' return to the treating doctor for discussion and decision making.

Separation and quantitative determination of 6α-hydroxycortisol and 6ß-hydroxycortisol in human urine by high-performance liquid chromatography with ultraviolet absorption detection.

The present study developed an high-performance liquid chromatography (HPLC) method for the simultaneous determination of urinary metabolites of endogenous cortisol, 6α-hydroxycortisol (6α-OHF) and 6ß-hydroxycortisol (6ß-OHF), in human urine, using 6α-hydroxycorticosterone as internal standard. 6α-OHF and 6ß-OHF were extracted from urine with ethyl acetate by using a Sep-Pak C(18) plus cartridge. Separation of the stereoisomers was achieved on a reversed-phase hybrid column by a gradient elution of (A) 0.05 M KH(2)PO(4)-0.01 M CH(3)COOH (pH 3.77) and (B) 0.05 M KH(2)PO(4)-0.01 M CH(3)COOH/acetonitrile (2:3, v/v). 6α-OHF and 6ß-OHF were well separated on an XTerra MS C(18) 5 µm column using two types of stepwise gradient elution program (programs 2 and 3). Resolutions of 6α-OHF and 6ß-OHF were Rs = 4.41 for program 2 and Rs = 4.60 for program 3. The analysis was performed within 23~26 min, monitored by UV absorbance at 239 nm. The lower limits of detection of 6α-OHF and 6ß-OHF were 0.80 ng per injection (s/n = ca. 8), and the lower limits of quantification were 5.02 ng/ml for 6α-OHF and 41.08 ng/ml for 6ß-OHF, respectively. The within-day reproducibilities in the amounts of 6α-OHF and 6ß-OHF determined were in good agreement with the actual amounts added, the relative errors being -5.37% and -3.73% (gradient 2) and -5.69% and -3.96% (gradient 3) for both 6α-OHF and 6ß-OHF, respectively. The inter-assay precisions (RSDs) for 6α-OHF and 6ß-OHF were less than 1.99% (gradient 2) and 2.61% (gradient 3), respectively. The present HPLC method was applied to the measurement of 6α-OHF and 6ß-OHF in urine to evaluate the time courses of 6α-hydroxylation and 6ß-hydroxylation clearances of cortisol during 40 days for phenotyping CYP3A in a healthy subject.

Transformative possibilities of communication in medical error cases in Japan.

OBJECTIVE: This study examines perceptions of persons who experienced a medical error and elements that may serve to open communication with those who experienced a medical error in Japan. DESIGN: Survey of individuals who reported a previous medical error in their care and those who did not. SETTING: Tokyo, Osaka and Nagoya metropolitan areas, and in Fukuoka, Shimane and Miyagi rural townships in Japan. PARTICIPANTS: Questionnaires were distributed to 80 people who had experienced a medical error and 300 people who had not. MAIN OUTCOME MEASURES: Prevalence of views, expectations and psychological needs regarding medical error. RESULTS: Forty (50%) questionnaires from those who experienced the errors and 201 (67%) from those who did not experience a medical error were completed. Among those who experienced error, 95% (38/40) preferred to be informed of a medical error immediately by senior personnel (57.7%: 23/40). Those who had not experienced error preferred to be informed by a directly responsible provider (87.6%: 176/201). The perception differences regarding who should break bad news showed statistical significance (P<0.001). Respondents reports that 'communication', 'apology' and 'corrective actions' can contribute to promoting resolution. CONCLUSIONS: This study showed that after the immediate disclosure of a medical error by senior medical personnel and medical providers should create an environment to continue 'communication' in order to accommodate shifting perspectives of those who experienced the error.

The influence of medical jargon mixed with foreign terminology in the Japanese clinical environment.

OBJECTIVES: To identify patient reports about their difficulties with medical jargon, to classify the most problematic types, and to examine the socio-demographic factors associated with them. METHODS: A cross-sectional nationwide survey (October 6 and November 4, 2004) was conducted. Out of 4,500 Japanese people (aged 15 years and older) who had seen physicians, 3,090 agreed to participate (response rate: 69%). Participants were asked the following: "Do you find physicians that use medical jargon difficult to understand?" and "What type of words did your physician use that required further explanation or clarification?" RESULTS: Of 3,090 respondents, 1,117 participants (36.1%; 95% confidence interval, 34.5-37.8%) reported difficulties understanding medical jargon. Those between the ages of 30 and 49 years, self-employed workers, homemakers, and unemployed individuals experienced the most difficulties. Difficult jargon included: 1) technical Japanese words, such as Kakutan Saibo-shin (sputum cytology) (57% of participants); 2) English medical terminology, such as clinical path (57%); and 3) English medical abbreviations, such as EBM (47%). CONCLUSIONS: In addition to avoiding technical words when communicating with their patients, Japanese physicians should consider the unique medical situation in which foreign terminology and abbreviations are used in Japan. Translation of foreign terminology into Japanese can be helpful for patients. Physicians should take the initiative to educate patients and familiarize them with foreign terminology and abbreviations.