Risk of major birth defects after first-trimester exposure to carbocisteine and ambroxol: A multicenter prospective cohort study using counseling data for drug safety during pregnancy.

To assess the risk of major birth defects after first-trimester exposure to carbocisteine and ambroxol during pregnancy, we conducted a prospective cohort study using counseling data for drug use during pregnancy provided by the Japan Drug Information Institute in Pregnancy and Toranomon Hospital. Counseling information, including drug usage and participants' demographic information, was collected between April 1988 and December 2017. Pregnancy outcome data, including major birth defects, were obtained using a questionnaire administered 1 month after delivery. The risks of major birth defects after first-trimester exposure to carbocisteine (n = 588) and ambroxol (n = 341) were compared with those of nonteratogenic drug use during the first trimester (n = 1525). The adjusted odds ratio (aORs) for major birth defects was calculated using a multiple logistic regression analysis adjusted for confounders. The incidence of major birth defects was 1.2% (7/588) and 2.1% (7/341) in the carbocisteine and ambroxol groups, respectively, which was comparable to the control group (26/1525, 1.7%). Results of multiple logistic regression demonstrated similar nonsignificant risks for both carbocisteine (aOR: 0.66, 95% confidence interval [CI]: 0.40-1.1, p = 0.11) and ambroxol (aOR: 1.1, 95% CI: 0.18-7.2, p = 0.88). No specific major birth defects were reported in the carbocisteine or ambroxol groups. This study demonstrated that carbocisteine and ambroxol exposure during the first trimester was not associated with an increased risk of major birth defects. These results could help in counseling for the use of these drugs during pregnancy and further alleviate anxiety in patients.

Presenteeism and social interaction in the "new normal" in Japan: a longitudinal questionnaire study.

BACKGROUND: Although social interaction and social support during the "new normal" due to coronavirus disease 2019 (COVID-19) may be related to presenteeism, the effect between these factors has not been clear for Japanese workers. The aim of this study was to describe the presenteeism of Japanese workers with reference to social interaction and social support following the lifestyle changes due to COVID-19 and to assess whether social interaction and social support affected their presenteeism. METHODS: The data were obtained from internet panel surveys from October 2020. Descriptive statistics were calculated, and multiple linear regression was conducted using the data from the first, fourth and fifth surveys, which were conducted during October to November 2020, July to August 2021, and September to October 2021, respectively. To measure presenteeism, questions from "absenteeism and presenteeism questions of the World Health Organization's Heath and Work Performance Questionnaire", short version in Japanese was utilized. Multiple linear regressions were conducted to investigate the effects of social interaction and social support-related factors on presenteeism. RESULTS: A total of 3,407 participants were included in the analysis. The mean score of absolute presenteeism from the fifth survey was 58.07 (SD = 19.71). More time spent talking with family, a larger number of social supporters and a higher satisfaction level for social support were associated with a higher absolute presenteeism score. CONCLUSIONS: Our results suggested that social support reduced the presenteeism of the Japanese workers during the "new normal" due to the COVID-19 pandemic. Social interaction with family also relieved presenteeism.

Diagnostic errors in uncommon conditions: a systematic review of case reports of diagnostic errors.

OBJECTIVES: To assess the usefulness of case reports as sources for research on diagnostic errors in uncommon diseases and atypical presentations. CONTENT: We reviewed 563 case reports of diagnostic error. The commonality of the final diagnoses was classified based on the description in the articles, Orphanet, or epidemiological data on available references; the typicality of presentation was classified based on the description in the articles and the judgment of the physician researchers. Diagnosis Error Evaluation and Research (DEER), Reliable Diagnosis Challenges (RDC), and Generic Diagnostic Pitfalls (GDP) taxonomies were used to assess the factors contributing to diagnostic errors. SUMMARY AND OUTLOOK: Excluding three cases in that commonality could not be classified, 560 cases were classified into four categories: typical presentations of common diseases (60, 10.7 %), atypical presentations of common diseases (35, 6.2 %), typical presentations of uncommon diseases (276, 49.3 %), and atypical presentations of uncommon diseases (189, 33.8 %). The most important DEER taxonomy was "Failure/delay in considering the diagnosis" among the four categories, whereas the most important RDC and GDP taxonomies varied with the categories. Case reports can be a useful data source for research on the diagnostic errors of uncommon diseases with or without atypical presentations.

Roles considered important for hospitalist and non-hospitalist generalist practice in Japan: a survey study.

BACKGROUND: An increased focus on quality and patient safety has led to the evolution of hospitalists. The number of hospitalists covering ward and outpatient care is on the rise in Japan. However, it is unclear what roles hospital workers themselves consider important in their practice. Therefore, this study investigated what hospitalists and non-hospitalist generalists in Japan consider important for the practice of their specialty. METHODS: This was an observational study that included Japanese hospitalists (1) currently working in a general medicine (GM) or general internal medicine department and (2) working at a hospital. Using originally developed questionnaire items, we surveyed the items important to hospitalists and non-hospitalist generalists. RESULTS: There were 971 participants (733 hospitalists, 238 non-hospitalist) in the study. The response rate was 26.1%. Both hospitalists and non-hospitalists ranked evidence-based medicine as the most important for their practice. In addition, hospitalists ranked diagnostic reasoning and inpatient medical management as the second and third most important roles for their practice, while non-hospitalists ranked inpatient medical management and elderly care as second and third. CONCLUSIONS: This is the first study investigating the roles Japanese hospitalists consider important and comparing those to that of non-hospitalist generalists. Many of the items that hospitalists considered important were those that hospitalists in Japan are working on within and outside academic societies. We found that diagnostic medicine and quality and safety are areas that are likely to see further evolution as hospitalists specifically emphasized on them. In the future, we expect to see suggestions and research for further enhancing the items that hospital workers value and emphasise upon.

Analysis of Adverse Events of Cholinesterase Inhibitors and NMDA Receptor Antagonists on Arrhythmias Using the Japanese Adverse Drug Event Report Database.

BACKGROUND: The association between anti-dementia drugs and arrhythmia is uncertain. In addition, the effects of certain drug combinations are not yet well known. OBJECTIVE: We investigated the association between anti-dementia drugs and arrhythmia. Furthermore, we investigated the effects of anti-dementia drugs both alone and in combination on the likelihood of arrhythmia in patients with dementia. METHODS: We examined the Japanese Adverse Drug Event Report database (JADER) from April 2004 to May 2022 for dementia drug users aged ≥ 60 years. We calculated the unadjusted reported odds ratio (ROR) and adjusted ROR for confounding factors. Furthermore, we examined the association of various combinations of anti-dementia drugs with the development of arrhythmias. RESULTS: There were 6718 arrhythmia cases identified out of 333,702 reported cases. The unadjusted ROR results were as follows: donepezil alone (ROR 4.39, 95% confidence interval [CI] 3.89-4.95), rivastigmine alone (2.10, 1.53-2.87), galantamine alone (3.87, 3.04-4.94), memantine alone (2.25, 1.59-3.20), and combination of choline esterase inhibitor and memantine (2.56, 1.84-3.57). In a multivariate analysis, the RORs remained significant. CONCLUSIONS: Regardless of whether anti-dementia drugs were used alone or in combination, attention should be paid to the occurrence of arrhythmias.

Five strategies on writing research papers for beginners and young general medicine doctors.

We propose five important strategies for young generalists to write original research and papers. We hope that even beginners will understand and practice these five strategies, and help young generalist to write research papers based on clinical questions that arise in their daily practice.

Identification of Prescribing Patterns in Hemodialysis Outpatients Taking Multiple Medications.

We investigated the relationship between multidrug administration and the characteristics, pathophysiology, and drug class in outpatients with hemodialysis. A retrospective cross-sectional study was conducted at Saitama Medical University Hospital in October 2018. Multidrug administration was defined as receiving either more than six drugs or more than the median number of drugs. The drugs used were represented by their anatomical classification codes in the Anatomical Therapeutic Chemistry Classification System (ATC classification). A latent class analysis (LCA) was used to identify clusters at risk of receiving multiple medications. A stepwise logistic regression analysis was performed to select ATC classifications prone to being involved in multidrug administration. As of October 2018, 98 outpatients with hemodialysis were enrolled in the study. In the LCA, when diabetes was the main primary disease, oral hypoglycemic agents available to dialysis patients were limited, but the number of drugs administered was large. Old age, poor nourishment, a long history of dialysis, and chronic nephritis were associated with multidrug administration among nondiabetic patients. In the second level of the ATC classification, the drugs frequently used were coded A02 (drugs for acid-related disorders), A07 (antidiarrheal agents, intestinal anti-inflammatory/anti-infective agents), B01 (antithrombotic agents), and N05 (psycholeptics). The prescribing patterns for either diabetic patients or nondiabetic elderly patients were identified in outpatients with hemodialysis taking multiple medications, and drugs for acid-related disorders, antidiarrheal agents, intestinal anti-inflammatory/anti-infective agents, antithrombotic agents, and psycholeptics are frequently used in those patients.

Impact of the cefazolin shortage on the selection and cost of parenteral antibiotics during the supply disruption period in Japan: A controlled interrupted time series analysis.

BACKGROUND: A serious shortage of cefazolin (CEZ) occurred in Japan in 2019. We compared the impact of the CEZ shortage on the selection of parenteral antibiotics at affected and non-affected hospitals. METHODS: The data were extracted from a nationwide Japanese administrative database and included all hospitalized cases between April 2016 and December 2020. We defined 'hospitals with shortage' as those hospitals with a statistically significant decrease in the use of CEZ during the supply disruption period compared to the same months of the previous year; other hospitals as 'hospitals without shortage'. We determined the proportion of each selected parenteral antibiotic use to the sum of all selected antibiotic use in the two groups of hospitals during the supply disruption period and during the same months of the previous year. A controlled interrupted time series (CITS) analysis was conducted to estimate the impact of the CEZ shortage on each antibiotic use and the cost of all parenteral antibiotics per patient day in hospitals with shortage as compared to those without shortage. RESULTS: In the hospitals with shortage, the proportion of CEZ use to the sum of all selected antibiotics decreased (23.5-11.1%). The decrease in CEZ use was mainly offset by the use of ceftriaxone, ceftriaxone, and ampicillin/sulbactam. The CITS analysis showed a statistically significant increase in the use of broader-spectrum beta-lactams and clindamycin during the supply disruption period (flomoxef up 58.1%, cefotiam up 63.1%, cefmetazole up 14.5%, ceftriaxone up 13.9%, and clindamycin up 20.1%). The analysis showed no statistically significant change in the cost of all parenteral antibiotics per patient day. CONCLUSIONS: During the CEZ supply disruption, there was a statistically significant increase in the use of broader-spectrum beta-lactams and clindamycin in hospitals with shortage compared with those without shortage.

Real opinions on general medicine residency programs in Japan: Perspectives from medical students, residents, and young academic generalists.

Medical students and junior residents have five concerns about general medicine training, and senior residents and young academic generalists respond to these concerns. We hope that this paper will help to dispel some common concerns for those who wish to become specialists in general medicine.

Renally inappropriate medications in elderly outpatients and inpatients with an impaired renal function.

BACKGROUND AND AIMS: The purpose of this study was to investigate differences in the frequency of renally inappropriate medications (RIMs) in outpatient and inpatient among three institutions. METHODS: We collected prescription and renal function data for patients over 65 years of age from the drug department system. We selected 50 kinds of the most frequently used medicines which require dose adjustment according to a patient's renal function. RESULTS: Outpatient RIM was seen in 611 cases (6.17%), and inpatient prescription RIM was seen in 317 cases (5.29%), showing a significant difference between the groups (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.02-1.35). However, in a multivariate analysis, when the renal function was included, that difference between outpatients and inpatients became insignificant (OR 1.16, 95% CI 0.98-1.37). The distribution of prescription with or without RIM in outpatient and inpatient settings depended on the CKD stage. Outpatients with a better CKD stage (stage 1-3) had a higher rate of RIM than inpatients, while patients with a worse CKD stage (stage 4 or 5) had a higher rate of RIM than outpatients. CONCLUSION: The rate of RIM in outpatients tends to be high, and attention should be paid to RIM in inpatients with a severe CKD stage.

Increasing the Status of Hospital General Medicine Departments with Emphasis on Outpatient Care in Japan.

Demand is increasing for general medicine services in Japan, a super-aged society. The new medical specialty system introduced in 2019 obligates physicians to obtain a qualified specialty from among 19 basic specialty fields, including general medicine, before obtaining more advanced qualified subspecialties. The role of the department of general medicine in Japan varies in each hospital. Remuneration for medical services obtained by general medicine departments that mainly provide outpatient care is relatively low, making it difficult to fill positions in this department within a hospital. We conducted a narrative review and discussed ways to increase the status of hospital general medicine departments that mainly provide outpatient care. We consider the following four points to be important: improvement of diagnostic capabilities in the outpatient setting; playing a central role in education for medical students and residents; active involvement with patients who have diagnostic difficulties or social problems; and branding and promotion of the general medicine department. We envision that adopting an active approach to these points will increase the status of general medicine departments that mainly provide outpatient care within the hospital, allowing such newly established departments to start easily in Japanese hospitals in the future.

Competencies for on-call physicians for home medical care: A qualitative study of home care providers' experiences in Japan's super-aged society.

Background: In Japan, many older people hope to receive end-of-life care at home. In such situations, team-based home medical care with the support of on-call physicians is needed. However, to date, necessary competencies for the on-call physicians have yet to be clarified. We aim to reveal the competencies for on-call physicians in home medical care settings. Method: This was a qualitative study of semi-structured interviews concerning competencies for on-call physicians in home medical care. We evaluated digitally recorded interviews with eight home care professionals in seven home care facilities (three clinics, one hospital, and three nursing agencies) in A City, Japan. The transcribed data were analyzed by three researchers using thematic analysis. Results: The competencies for on-call physicians were divided into the following six categories: clinical skills for frequent complaints, collecting patients' information in advance, understanding purposes of home care, understanding general roles of home care health professionals, thoughtfulness toward patients' families, and an attitude of humility. Conclusion: These competencies were classified into disease-specific and interpersonal (collaborative) skills in home medical care. The competencies revealed by the study could contribute to the development of effective learning and preparation for on-call physicians who support home medical care.

Hospital at Home for Elderly COVID-19 Patients: A Preliminary Report with 100 Patients.

Hospital-at-home (HaH) care is useful for patients with COVID-19 and an alternative strategy when hospital capacity is under pressure due to patient surges. However, the efficacy and safety of HaH in elderly patients with COVID-19 remain unknown. In Kyoto city, we conducted a retrospective medical record review of HaH care focused on elderly COVID-19 patients from 4 February to 25 June 2021. Eligible patients were (1) COVID-19 patients aged ≥70 years and those who lived with them or (2) COVID-19 patients aged <70 years with special circumstances and those who lived with them. During the study period, 100 patients received HaH care. Their median age was 76 years (interquartile range 56−83), and 65% were over 70 years. Among 100 patients, 36 (36%) had hypoxia (oxygen saturation ≤ 92%), 21 (21%) received steroid medication, and 34 (34%) received intravenous fluids. Although 22 patients were admitted to the hospital and 3 patients died there, no patients died during HaH care. HaH care may be safe and effective in elderly patients with COVID-19. Our study shows that HaH provides an alternative strategy for treating COVID-19 patients and can reduce the healthcare burden at hospitals.

Large-Scale Observational Study on the Current Status and Challenges of General Medicine in Japan: Job Description and Required Skills.

PURPOSE: To identify the current ambiguous status of general medicine (GM) and assess current problems and weaknesses for further development of GM. PATIENTS AND METHODS: This study adopted an observational design. GM practitioners were selected from the mailing lists of two primary professional associations for Japanese GM doctors. We included physicians currently working in a GM department, those self-described as GM doctors, and those board-certified in family medicine or general internal medicine. Respondents replied to survey questions about their sociodemographic data, job descriptions, and the requisite skills for practice. GM doctors' job description and required skills were categorized into "clinical," "management," "education," and "research." Participants (n = 971) were compared based on job descriptions and important skills in each category by facility type, size, and position. RESULTS: "Clinical" was indicated as the most important category for both job description and important skills, followed by "management," "education," and "research." For job description details, "follow-up outpatient" (35.6%) ranked first for "clinical," and "resident education" (57.3%) ranked first for "education." By facility type and size, job description and important skills decreased for clinical and management categories as facility sizes increased; the opposite was true for "education." "Research" was generally rated low. By position, no significant difference was found in effort or importance given to research. CONCLUSION: This study is the first survey on GM physicians across Japan. The results show that while Japanese GM physicians focus on and place importance on clinical practice, they are less involved in research and do not consider research skills to be important. The challenge for the future development of GM lies in research.

Hospitalization for ischemic stroke was affected more in independent cases than in dependent cases during the COVID-19 pandemic: An interrupted time series analysis.

BACKGROUND: The pandemic of the coronavirus disease 2019 (COVID-19) has affected health care systems globally. The aim of our study is to assess the impact of the COVID-19 pandemic on the number of hospital admissions for ischemic stroke by severity in Japan. METHODS: We analysed administrative (Diagnosis Procedure Combination-DPC) data for cases of inpatients aged 18 years and older who were diagnosed with ischemic stroke and admitted during the period April 1 2018 to June 27 2020. Levels of change of the weekly number of inpatient cases with ischemic stroke diagnosis after the declaration of state of emergency were assessed using interrupted time-series (ITS) analysis. The numbers of patients with various characteristics and treatment approaches were compared. We also performed an ITS analysis for each group ("independent" or "dependent") divided based on components of activities of daily living (ADL) and level of consciousness at hospital admission. RESULTS: A total of 170,294 cases in 567 hospitals were included. The ITS analysis showed a significant decrease in the weekly number of ischemic stroke cases hospitalized (estimated decrease: -156 cases; 95% confidence interval (CI): -209 to -104), which corresponds to -10.4% (95% CI: -13.6 to -7.1). The proportion of decline in the independent group (-21.3%; 95% CI: -26.0 to -16.2) was larger than that in the dependent group (-8.6%; 95% CI: -11.7 to -5.4). CONCLUSIONS: Our results show a marked reduction in hospital admissions due to ischemic stroke after the declaration of the state of emergency for the COVID-19 pandemic. The independent cases were affected more in proportion than dependent cases.