Monitoring for adverse drug events of high-risk medications with a computerized clinical decision support system: a prospective cohort study.

Monitoring is recommended to prevent severe adverse drug events, but such examinations are often missed. To increase the number of monitoring that should be ordered for high-risk medications, we introduced a clinical decision support system (CDSS) that alerts and orders the monitoring for high-risk medications in an outpatient setting. We conducted a 2-year prospective cohort study at a tertiary care teaching hospital before (phase 1) and after (phase 2) the activation of a CDSS. The CDSS automatically provided alerts for liver function tests for vildagliptin, thyroid function tests for immune checkpoint inhibitors (ICIs) and multikinase inhibitors (MKIs), and a slit-lamp examination of the eyes for oral amiodarone when outpatients were prescribed the medications but not examined for a fixed period. The order of laboratory tests automatically appeared if alert was accepted. The alerts were hidden and did not appear on the display before activation of the CDSS. The outcomes were the number of prescriptions with alerts and examinations. During the study period, 330 patients in phase 1 and 307 patients in phase 2 were prescribed vildagliptin, 20 patients in phase 1 and 19 patients in phase 2 were prescribed ICIs or MKIs, and 72 patients in phase 1 and 66 patients in phase 2 were prescribed oral amiodarone. The baseline characteristics were similar between the phases. In patients prescribed vildagliptin, the proportion of alerts decreased significantly (38% vs 27%, P < 0.0001), and the proportion of examinations increased significantly (0.9% vs 4.0%, P < 0.0001) after activation of the CDSS. In patients prescribed ICIs or MKIs, the proportion of alerts decreased significantly (43% vs 11%, P < 0.0001), and the proportion of examinations increased numerically, but not significantly (2.6% vs 7.0%, P = 0.13). In patients prescribed oral amiodarone, the proportion of alerts decreased (86% vs 81%, P = 0.055), and the proportion of examinations increased (2.2% and 3.0%, P = 0.47); neither was significant. The CDSS has potential to increase the monitoring for high-risk medications. Our study also highlighted the limited acceptance rate of monitoring by CDSS. Further studies are needed to explore the generalizability to other medications and the cause of the limited acceptance rates among physicians.

Association Between Statins and Cancer Incidence in Diabetes: a Cohort Study of Japanese Patients with Type 2 Diabetes.

BACKGROUND: The antitumor effect of statins has been highlighted, but clinical study results remain inconclusive. While patients with diabetes are at high risk of cancer, it is uncertain whether statins are effective for cancer chemoprevention in this population. OBJECTIVE: This study evaluated the association between statins and cancer incidence/mortality in patients with type 2 diabetes. DESIGN: This study was a follow-up observational study of the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, which was a randomized controlled trial of low-dose aspirin in Japanese patients with type 2 diabetes. PARTICIPANTS: This study enrolled 2536 patients with type 2 diabetes, age 30-85 years, and no history of atherosclerotic cardiovascular disease, from December 2002 until May 2005. All participants recruited in the JPAD trial were followed until the day of any fatal event or July 2015. We defined participants taking any statin at enrollment as the statin group (n = 650) and the remainder as the no-statin group (n = 1886). MAIN MEASURES: The primary end point was the first occurrence of any cancer (cancer incidence). The secondary end point was death from any cancer (cancer mortality). KEY RESULTS: During follow-up (median, 10.7 years), 318 participants developed a new cancer and 123 died as a result. Cancer incidence and mortality were 10.5 and 3.7 per 1000 person-years in the statin group, and 16.8 and 6.3 per 1000 person-years in the no-statin group, respectively. Statin use was associated with significantly reduced cancer incidence and mortality after adjustment for confounding factors (cancer incidence: adjusted hazard ratio [HR], 0.67; 95% CI, 0.49-0.90, P = 0.007; cancer mortality: adjusted HR, 0.60; 95% CI, 0.36-0.98, P = 0.04). CONCLUSIONS: Statin use was associated with a reduced incidence and mortality of cancer in Japanese patients with type 2 diabetes.

Antipsychotic Polypharmacy Is Associated With Adverse Drug Events in Psychiatric Inpatients: The Japan Adverse Drug Events Study.

BACKGROUND: Antipsychotic (AP) polypharmacy (APP), the coprescription of more than 1 AP, is frequently practiced in psychiatric inpatients and is considered to be a risk factor for adverse drug events (ADEs). However, the association between APP and ADEs among psychiatric inpatients has not been well investigated. METHODS: The Japan Adverse Drug Events (JADE) study was a series of cohort studies conducted in several clinical settings. In particular, the JADE study for psychiatric inpatients was a retrospective cohort study of 448 psychiatric inpatients with a cumulative 22,733 patient-days. We investigated the relationship between APP, defined as a concurrent prescription of 2 or more APs and ADEs. We also assessed the relationship between potential risk factors for ADEs due to APs. RESULTS: Among the 448 patients included in this study, 106 patients (24%) had APP and the remaining 342 patients were prescribed 1 AP or none. Risperidone was the most frequent drug (25%, 109/442 AP prescriptions) used, and levomepromazine was most frequently prescribed as a concurrent medication with other APs (91%, 29/32). The median number of ADEs among the patients with APP was significantly higher than in those without APP (P = 0.001). Antipsychotic polypharmacy was a risk factor for the occurrence of first (adjusted hazard ratio, 1.54; 95% confidence interval, 1.15-2.04) and second (adjusted hazard ratio, 1.99; 95% confidence interval, 1.40-2.79) ADEs. CONCLUSIONS: Antipsychotic polypharmacy was a risk factor for the occurrence of single and multiple ADEs. Antipsychotic polypharmacy should be conservatively and minimally practiced.

Treatment with anagliptin, a DPP-4 inhibitor, decreases FABP4 concentration in patients with type 2 diabetes mellitus at a high risk for cardiovascular disease who are receiving statin therapy.

BACKGROUND: Fatty acid-binding protein 4 (FABP4) acts as a novel adipokine, and elevated FABP4 concentration is associated with obesity, insulin resistance and atherosclerosis. Dipeptidyl peptidase-4 (DPP-4) inhibitors, a class of antidiabetic drugs, have distinct structures among the drugs, possibly leading to a drug class effect and each drug effect. Sitagliptin, a DPP-4 inhibitor, has been reported to decrease FABP4 concentration in drug-naïve and sulfonylurea-treated patients with type 2 diabetes mellitus. Anagliptin, another DPP-4 inhibitor, was shown to decrease low-density lipoprotein cholesterol (LDL-C) level to a greater extent than that by sitagliptin in the Randomized Evaluation of Anagliptin vs. Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial. AIM AND METHODS: As a sub-analysis study using data obtained from the REASON trial, we investigated the effects of treatment with anagliptin (n = 148, male/female: 89/59) and treatment with sitagliptin (n = 159, male/female: 93/66) for 52 weeks on FABP4 concentration in patients with type 2 diabetes mellitus at a high risk for cardiovascular events who were receiving statin therapy. RESULTS: The DPP-4 inhibitor had been administered in 82% of the patients in the anagliptin group and 81% of the patients in sitagliptin group prior to randomization. Serum FABP4 level was significantly decreased by 7.9% by treatment with anagliptin (P = 0.049) and was not significantly decreased by treatment with sitagliptin (P = 0.660). Change in FABP4 level was independently associated with basal FABP4 level and changes in waist circumference and creatinine after adjustment of age, sex and the treatment group. CONCLUSION: Anagliptin decreases serum FABP4 concentration independent of change in hemoglobin A1c or LDL-C in patients with type 2 diabetes mellitus and dyslipidemia who are on statin therapy. Trial registration ClinicalTrials.gov number NCT02330406. Registered January 5, 2015, https://clinicaltrials.gov/ct2/show/NCT02330406.

Differences in lipid metabolism between anagliptin and sitagliptin in patients with type 2 diabetes on statin therapy: a secondary analysis of the REASON trial.

BACKGROUND: Anagliptin, a dipeptidyl peptidase-4 inhibitor, is reported to reduce the level of low-density lipoprotein cholesterol (LDL-C). The underlying mechanism of this effect and effect on lipid metabolism however remains uncertain. AIM AND METHODS: We therefore evaluate the effects of anagliptin on lipid metabolism-related markers compared with those of sitagliptin. The study was a secondary analysis using data obtained from the Randomized Evaluation of Anagliptin versus Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial. This trial in patients with type 2 diabetes at a high risk of cardiovascular events and on statin therapy showed that anagliptin reduced LDL-C levels to a greater extent than sitagliptin. Cholesterol absorption (campesterol and sitosterol) and synthesis (lathosterol) markers were measured at baseline and 52 weeks in the study cohort (n = 353). RESULTS: There was no significant difference in the changes of campesterol or sitosterol between the two treatment groups (p = 0.85 and 0.55, respectively). Lathosterol concentration was increased significantly at 52 weeks with sitagliptin treatment (baseline, 1.2 ± 0.7 µg/mL vs. 52 weeks, 1.4 ± 1.0 µg/mL, p = 0.02), whereas it did not change in the anagliptin group (baseline, 1.3 ± 0.8 µg/mL vs. 52 weeks, 1.3 ± 0.7 µg/mL, p = 0.99). The difference in absolute change between the two groups showed a borderline significance (p = 0.06). CONCLUSION: These findings suggest that anagliptin reduces LDL-C level by suppressing excess cholesterol synthesis, even in combination with statin therapy. Trial registration ClinicalTrials.gov number NCT02330406. https://clinicaltrials.gov/ct2/show/NCT02330406; registered January 5, 2015.

Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Patients With Type 2 Diabetes Mellitus: 10-Year Follow-Up of a Randomized Controlled Trial.

BACKGROUND: The long-term efficacy and safety of low-dose aspirin for primary prevention of cardiovascular events in patients with type 2 diabetes mellitus are still inconclusive. METHODS: The JPAD trial (Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes) was a randomized, open-label, standard care-controlled trial examining whether low-dose aspirin affected cardiovascular events in 2539 Japanese patients with type 2 diabetes mellitus and without preexisting cardiovascular disease. Patients were randomly allocated to receive aspirin (81 or 100 mg daily; aspirin group) or no aspirin (no-aspirin group) in the JPAD trial. After that trial ended in 2008, we followed up with the patients until 2015, with no attempt to change the previously assigned therapy. Primary end points were cardiovascular events, including sudden death, fatal or nonfatal coronary artery disease, fatal or nonfatal stroke, and peripheral vascular disease. For the safety analysis, hemorrhagic events, consisting of gastrointestinal bleeding, hemorrhagic stroke, and bleeding from any other sites, were also analyzed. The primary analysis was conducted for cardiovascular events among patients who retained their original allocation (a per-protocol cohort). Analyses on an intention-to-treat cohort were conducted for hemorrhagic events and statistical sensitivity. RESULTS: The median follow-up period was 10.3 years; 1621 patients (64%) were followed up throughout the study; and 2160 patients (85%) retained their original allocation. Low-dose aspirin did not reduce cardiovascular events in the per-protocol cohort (hazard ratio, 1.14; 95% confidence interval, 0.91-1.42). Multivariable Cox proportional hazard model adjusted for age, sex, glycemic control, kidney function, smoking status, hypertension, and dyslipidemia showed similar results (hazard ratio, 1.04; 95% confidence interval, 0.83-1.30), with no heterogeneity of efficacy in subgroup analyses stratified by each of these factors (all interaction P>0.05). Sensitivity analyses on the intention-to-treat cohort yielded consistent results (hazard ratio, 1.01; 95% confidence interval, 0.82-1.25). Gastrointestinal bleeding occurred in 25 patients (2%) in the aspirin group and 12 (0.9%) in the no-aspirin group (P=0.03), and the incidence of hemorrhagic stroke was not different between groups. CONCLUSIONS: Low-dose aspirin did not affect the risk for cardiovascular events but increased risk for gastrointestinal bleeding in patients with type 2 diabetes mellitus in a primary prevention setting. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00110448.

Fruit intake reduces the onset of respiratory allergic symptoms in schoolchildren.

BACKGROUND: Previous studies have shown that dietary pattern is associated with allergy prevention. METHODS: We conducted a prospective cohort study on all primary schools in Omihachiman City, Shiga Prefecture, Japan. Questionnaires regarding allergic symptoms and diet were distributed to the parents of all 759 7-year-old schoolchildren for 4 consecutive years, from 2011 to 2014. Specific immunoglobulin E to inhalant allergens was measured at 10 years of age. Participants were then categorized as low, medium, or high intake during the study period for four food groups (fruits, vegetables, fish, and beans). Logistic regression analysis was performed to estimate odds ratios and 95% confidence intervals. RESULTS: A total of 520 children (68.5%) whose parents responded to the questionnaires all 4 years were included in the analysis. The prevalence of asthma, rhinitis, and any allergic symptoms at age 10 was significantly decreased with increases in fruit intake. In addition, the onset of any allergic symptoms during the study period was significantly decreased with increases in fruit intake (33.3%, 28.3%, and 14.3% in children with low, medium, and high fruit intake, respectively; P for trend =.01). The sensitization rate to ragweed at age 10 was significantly decreased with increases in fruit intake (P for trend =.046). No significant effect was observed for the other three food groups, except for the association between fish intake and new-onset asthma symptoms. CONCLUSIONS: These findings suggest that higher intake of fruit can help prevent respiratory allergic symptoms in schoolchildren.

Acquired palatal groove and delayed oral feeding in preterm infants.

BACKGROUND: Acquired palatal groove has been reported in the 1970s and 1980s, but its current incidence in Japanese newborns is unclear. The aims of this study were to determine the incidence of palatal groove in preterm infants and to evaluate whether this condition affects oral feeding ability. METHODS: We conducted a prospective observational study among very low-birthweight infants born at Takatsuki General Hospital, Osaka, between March and October in 2010. The shape of the hard palate was classified into three types: normal, narrow high-arched palate, and palatal groove. RESULTS: Among the 37 enrolled infants, 14 (38%) had palatal groove. In particular, among the 29 infants with birthweight <1000 g, palatal groove was observed in 48% of these patients, and only 10% were normal. Infants with palatal groove were ventilated for considerably more days with oral endotracheal tube than those without palate groove, even after adjustment for gestational age, birthweight, and duration of oral duodenal tube placement (OR, 1.11). Establishment of oral feeding and disappearance of choking on milk were considerably delayed in infants with palatal groove. Transient oral feeding difficulty requiring thickened-feed intervention was observed only in infants with palatal groove; on multi-regression analysis this difficulty seemed to be induced by the palatal groove. CONCLUSIONS: Palatal groove formation induced by oral endotracheal intubation occurs with a high frequency in preterm infants, and this is likely to affect oral feeding ability.

Effect of Volume Guarantee in Preterm Infants on High-Frequency Oscillatory Ventilation: A Pilot Study.

Objectives Although adding volume guarantee (VG) to conventional ventilation has been a well-established respiratory management for preterm infants, the evidence of VG combined with high-frequency oscillatory ventilation (HFOV) has not been studied well. The aim of this study was to investigate the effect of VG added to HFOV on respiratory and other physiological parameters. Methods We conducted a pilot study in extremely low-birth-weight infants ventilated with HFOV + VG with stable pulmonary status after 28 days of age. VG was applied for 6 hours and removed for the following 6 hours, and data were collected during these 12 hours. Results Six neonates were included in this study (gestational age: 22w5d-23w6d, birthweight: 424-584 g). High-frequency expired tidal volume per weight and amplitude were similar between periods with and without VG. Fluctuation of SpO2, but not heart rate, was significantly smaller when babies were ventilated with VG than without VG. Fluctuation of minute volume and carbon dioxide diffusion coefficient significantly increased after VG removal. The proportion of time with SpO2 < 80% was decreased by VG overall, especially in three cases. Conclusion This pilot study suggests VG combined with HFOV attenuates fluctuation of SpO2 and CO2 clearance, which may prevent hypoxemia and hypocapnia.

Sports activities enhance the prevalence of rhinitis symptoms in schoolchildren.

BACKGROUND: To evaluate the association between sports activities and allergic symptoms, especially rhinitis, among schoolchildren. METHODS: This longitudinal survey of schoolchildren collected data from questionnaires regarding allergic symptoms based on the International Study of Asthma and Allergies in Childhood (ISAAC) program and sports participation that were distributed to the parents of children at all 12 public primary schools in Ohmi-Hachiman City, Shiga Prefecture, Japan. Data were collected annually from 2011 until 2014, when the children reached 10 years of age. Blood samples were obtained in 2014, and the levels of immunoglobulin (Ig)E specific to four inhalant allergens were measured. RESULTS: Data from 558 children were analyzed. At 10 years of age, prevalence of asthma and eczema did not differ significantly, while rhinitis was significantly higher (p = 0.009) among children who participated in sports. Prevalence of rhinitis increased as the frequency or duration of sports participation increased (p < 0.01). The prevalence of new-onset rhinitis increased significantly among 10-year-olds with increasing duration of participation in sports (p = 0.03). Among those who participated in continuous sports activities, the prevalence of rhinitis was significantly higher with prolonged eczema (p = 0.006). Sports activities did not increase sensitization to inhalant allergens. CONCLUSION: Sports activities enhance the prevalence of rhinitis in schoolchildren. Prolonged eczema, together with sports participation, further promotes the symptoms. The mechanisms of these novel findings warrant further investigation.

The epidemiology of adverse drug events and medication errors among psychiatric inpatients in Japan: the JADE study.

BACKGROUND: Knowledge of the epidemiology of adverse drug events (ADEs) and medication errors in psychiatric inpatients is limited outside Western countries. The nature of ADEs and medication errors are important for improving the quality of care worldwide; therefore, we conducted the Japan Adverse Drug Events Study, a series of cohort studies at several settings in Japan. METHODS: This report included 448 inpatients with 22,733 patient-days in a psychiatric hospital and psychiatric units at a tertiary care teaching hospital over 1 year. Four psychiatrists and two other physicians reviewed all medical charts and related documents to identify suspected incidents. The physicians later classified those incidents into ADEs, potential ADEs, medication errors, or exclusions and evaluated the severity and preventability if the incidents were events. RESULTS: During the study period, we identified 955 ADEs and 398 medication errors (incidence: 42.0 and 17.5 per 1000 patient-days, respectively). Among ADEs, 1.4 %, 28 %, and 71 % were life-threatening, serious, and significant, respectively. Antipsychotics were associated with half of all ADEs. The incidence of medication errors was higher in medical care units than in acute and nursing care units (40.9, 15.6, and 17.4 per 1000 patient-days, respectively). The monitoring and ordering stages were the most common error stages (39 % and 34 % of all medication errors, respectively), and 76 % of medication errors with ADEs were found at the monitoring stage. Non-psychiatric drugs were three times as likely to cause ADEs with errors compared to psychiatric drugs. CONCLUSIONS: Antipsychotic use, inadequate monitoring, and treatment of physical ailments by psychiatrists may contribute to the high incidence of medication errors and ADEs among psychiatric inpatients in Japan. Psychiatrists should be cautious in prescribing antipsychotics or unfamiliar medications for physical problems in their psychiatric patients, and should monitor patients after medication administration.

Prenatal vitamin A supplementation associated with adverse child behavior at 3 years in a prospective birth cohort in Japan.

BACKGROUND: Many pregnant women take vitamin supplements during pregnancy. The aim of this paper was to clarify the effects of dietary supplementation prior to and/or during pregnancy on child behavior. METHODS: A prospective birth cohort study from pregnancy to 3 years of age involving 1271 pairs of Japanese pregnant women and their newborns, was carried out. The women completed a self-administered questionnaire during the third trimester of pregnancy. To evaluate deviations in child behavior as an endpoint, each mother completed the Japanese Child Behavior Checklist for ages 2-3 years after 3 years of birth. Participant characteristics were compared between supplement takers and non-takers. RESULTS: Among many kinds of supplements, intake of supplemental vitamin A/ß-carotene prior to and/or during pregnancy was associated with hazardous effects on child behavior at 3 years of age (total t-score, P = 0.003; internal t-score, P = 0.027; external t-score, P = 0.013). This association held true even after adjusting for age, number of deliveries, infertility treatment, consumption of fast food, smoking status, maternal and paternal education, maternal and paternal income, gestational age at birth, anthropometry at birth (weight, height, head circumference and body circumference), and the State-Trait Anxiety Inventory at 3 years of age by means of multiple imputation. CONCLUSIONS: Intake of supplemental vitamin A prior to and/or during pregnancy may worsen child behavior at 3 years of age.

An individual patient data meta-analysis on factors associated with adverse drug events in surgical and non-surgical inpatients.

AIM: The incidence of adverse drug events (ADEs) in surgical and non-surgical patients may differ. This individual patient data meta-analysis (IPDMA) identifies patient characteristics and types of medication most associated with patients experiencing ADEs and suggests target areas for reducing harm and implementing focused interventions. METHODS: Authors of eligible studies on preventable ADEs (pADEs) were approached for collaboration. For assessment of differences among (non-)surgical patients and identification of associated factors descriptive statistics, Pearson chi-square, Poisson and logistic regression analyses were performed. For identification of high risk drugs (HRDs), a model was developed based on frequency, severity and preventability of medication related to ADEs. RESULTS: Included were 5367 patients from four studies. Patients aged ≥ 77 years experienced more ADEs and pADEs compared with patients aged ≤ 52 years (odds ratios (OR) 2.12 (95% CI 1.70, 2.65) and 2.55 (95% CI 1.70, 3.84), respectively, both P < 0.05). Polypharmacy on admission also increased the risk of ADEs (OR 1.21 (95% CI 1.03, 1.44), P < 0.05) and pADEs (OR 1.85 (95% CI 1.34, 2.56), P < 0.05). pADEs were associated with more severe harm than non-preventable ADEs (54% vs. 32%, P < 0.05). The top five HRDs were antibiotics, sedatives, anticoagulants, diuretics and antihypertensives. Events associated with HRDs included diarrhoea or constipation, abnormal liver function test and central nervous system events. Most pADEs resulted from prescribing errors (90%). CONCLUSION: Elderly patients with polypharmacy on admission and receiving antibiotics, sedatives, anticoagulants, diuretics or antihypertensives were more prone to experiencing ADEs. Efficiency in prevention of ADEs may be improved by targeted vigilance systems for alertness of physicians and pharmacists.

Influence of adverse drug events on morbidity and mortality in intensive care units: the JADE study.

OBJECTIVE: To identify the influence of adverse drug events (ADEs) on morbidity and mortality in intensive care units (ICUs). DESIGN: A prospective cohort study. SETTING: ICU setting at three acute care hospitals in Japan. PARTICIPANTS: All patients aged ≥15 years were admitted to all ICUs during a 6-month study period. INTERVENTION: No intervention. MAIN OUTCOME MEASURES: Mortality in the ICUs and the length of the ICU stay. . RESULTS: We included 459 patients with a total of 3231 patient-days. Ninety-nine ADEs occurred in 70 patients (15%), so that the incidence of ADEs was 30.6 per 1000 patient-days and 21.6 ADEs per 100 admissions. Seventy-three patients (16%) died during their ICU stay. Excluding 38 deaths within 3 days after admission, 12 patients (17%) died among the 70 patients who had at least one ADE during their ICU stay and 23 (7%) died among 351 without an ADE (P = 0.003). The median ICU length of stay was 3 days. Excluding 73 patients who died during their ICU stay, the median ICU stay of patients with at least one ADE was 13 days, while it was only 2 days in the remainder (P < 0.0001). ADEs were associated with longer length of ICU stay but not with mortality even after adjusting for patients' severity of illness. CONCLUSIONS: ADEs were common in ICUs and significantly associated with longer length of ICU stay but did not influence on mortality.

Public attitudes toward practice by medical students: a nationwide survey in Japan.

BACKGROUND: It is essential for medical students to interact directly with patients. However, patients may be reluctant to be seen by medical students in settings in which they may also be seen by senior staff. PURPOSES: To understand patients' attitudes toward practice by medical students and consider the factors involved in obtaining patients' cooperation, we conducted a nationwide cross-sectional survey. METHODS: We randomly selected 2,400 adult participants from all over Japan. Trained research assistants inquired about participants' experiences and attitudes toward practice by medical students using a questionnaire. We compared differences in attitudes between participants who were accepting of practice by medical students and those who were not, as well as differences between participants who had experienced practice by a medical student versus those who had not. RESULTS: A total of 1,109 (46%) participants were included in the study. Eleven percent (117/1109) of the participants had experienced practice by a medical student. One fourth of participants were accepting of practice by medical students, and experienced participants were significantly more likely to be accepting of practice by medical students than inexperienced participants (45% vs. 24%, p<.001). Impressions of practice by medical students among accepting participants with previous experiences included "polite," "kind," and "hard-working." Fifty-nine percent (637/1088) of participants indicated that they would request a senior staff member's supervision when being seen by a medical student. CONCLUSIONS: The present nationwide survey suggests that education emphasizing bedside manner may be effective in promoting patients' cooperation of medical students. In addition, providing information to patients about medical students and efforts to increase supervision during clinical clerkship should be emphasized to foster the public's cooperation.

Adverse Events in Pediatric Inpatients: The Japan Adverse Event Study.

OBJECTIVES: Adverse events (AEs) represent an important cause of morbidity and mortality for pediatric inpatients; however, reports on their epidemiology in pediatrics, especially outside Western countries, are scarce. We investigated the incidence and nature of AEs in pediatric inpatients in Japan. METHODS: Trained pediatrician and pediatric nurses reviewed all medical documents of 1126 pediatric inpatients in 2 tertiary care teaching hospitals in Japan, and potential incidents were collected with patients' characteristics. Age was categorized into 6 groups (neonates, infants, preschoolers, school-aged children, teenagers, and over-aged pediatric patients), and medical care when potential incidents occurred was classified into drug, operation, procedure/examinations, nursing, management, and judgment. Physician reviewers independently evaluated all collected incidents into AEs, potential AEs, medical errors, and exclusions and assessed their severity and preventability. RESULTS: A total of 1126 patients with 12,624 patient-days were enrolled, and 953 AEs, with an incidence of 76 (95% confidence interval, 71-80) per 1000 patient-days, were identified. Preventable AEs accounted for 23% (218/953) of AEs. The incidence of AEs tended to decrease with increasing age. The proportion of AEs that were preventable was highest in neonates (40%), and this proportion decreased as children aged. Both judgment and management-related AEs were considered preventable AEs, and judgment-related AEs were more severe AEs than no-judgment-related AEs; 43% were life-threatening. CONCLUSIONS: Adverse events were common in Japanese pediatric inpatients, and their preventability and severity varied considerably by age category and medical care. Further investigation is needed to address which strategies might most improve pediatric patient safety.

Rationale and protocol for a prospective cohort study of respiratory viral infections in patients admitted from emergency departments of community hospitals: Effect of respiratory Virus infection on EmeRgencY admission (EVERY) study.

INTRODUCTION: Respiratory syncytial virus (RSV) is a causative virus for the common cold worldwide and can result in hospitalisations and even death in patients with high-risk conditions and older adults. However, the relationship between RSV or other incidental respiratory infections and acute exacerbations of underlying conditions has not been well investigated. The primary objective of this study is to estimate RSV prevalence, risk factors for adverse outcomes or hospitalisation and their effect on the hospital course of patients with acute respiratory symptoms admitted from emergency departments. Furthermore, we evaluate the prevalence of other respiratory viruses associated with respiratory symptoms. METHODS AND ANALYSIS: We are conducting a multicentre prospective cohort study in Japan. We plan to enrol 3000 consecutive patients admitted from emergency departments with acute respiratory symptoms or signs from 1 July 2023 to 30 June 2024. A nasopharyngeal swab is obtained within 24 hours of admission and the prevalence of RSV and other respiratory viruses is measured using the FilmArray Respiratory 2.1 panel. Paired serum samples are collected from patients with suspected lower respiratory infections to measure RSV antibodies at admission and 30 days later. Information on patients' hospital course is retrieved from the electronic medical records at discharge, death or 30 days after admission. Furthermore, information on readmission to the hospital and all-cause mortality is collected 180 days after admission. We assess the differences in clinical outcomes between patients with RSV or other respiratory viruses and those without, adjusting for baseline characteristics. Clinical outcomes include in-hospital mortality, length of hospital stay, disease progression, laboratory tests and management of respiratory symptoms or underlying conditions. ETHICS AND DISSEMINATION: The study protocol was approved by the institutional review boards of participating hospitals. Our study reports will be published in academic journals as well as international meetings. TRIAL REGISTRATION NUMBER: NCT05913700.

Effect of low-dose aspirin on primary prevention of cardiovascular events in Japanese diabetic patients at high risk.

BACKGROUND: Benefit of low-dose aspirin for primary prevention of cardiovascular events in diabetes remains controversial. The American Diabetes Association (ADA), the American Heart Association (AHA), and the American College of Cardiology Foundation (ACCF) recommend aspirin for high-risk diabetic patients: older patients with additional cardiovascular risk factors. We evaluated aspirin's benefit in Japanese diabetic patients stratified by cardiovascular risk. METHODS AND RESULTS: In the JPAD trial, we enrolled 2,539 Japanese patients with type 2 diabetes and no history of cardiovascular disease. We randomly assigned them to aspirin (81-100 mg daily) or no aspirin groups. The median follow-up period was 4.4 years. We stratified the patients into high-risk or low-risk groups, according to the US recommendation: age (older; younger) and coexisting cardiovascular risk factors. The risk factors included smoking, hypertension, dyslipidemia, family history of coronary artery disease, and proteinuria. Most of the patients were classified into the high-risk group, consisting of older patients with risk factors (n=1,804). The incidence of cardiovascular events was higher in this group, but aspirin did not reduce cardiovascular events (hazard ratio [HR], 0.83; 95% confidence interval [CI]: 0.58-1.17). In the low-risk group, consisting of older patients without risk factors and younger patients (n=728), aspirin did not reduce cardiovascular events (HR, 0.55; 95% CI: 0.23-1.21). These results were unchanged after adjusting for potential confounding factors. CONCLUSIONS: Low-dose aspirin is not beneficial in Japanese diabetic patients at high risk.