Two cases of iatrogenic levofloxacin-resistant pre-XDR tuberculosis in Japan.

This case report discusses two instances of iatrogenically induced pre-extensively drug-resistant tuberculosis (pre-XDR TB). In both cases, the patients were initially diagnosed with tuberculosis and hospitalized in university hospitals. Nucleic acid amplification tests identified rifampicin-resistant tuberculosis, leading to a deviation from clinical guidelines. Without prior verification of susceptibility to other drugs, levofloxacin was added to the standard antituberculosis regimen, which included isoniazid, pyrazinamide, ethambutol, and rifampicin. Subsequent phenotypic drug susceptibility tests (DST) revealed resistance to isoniazid but susceptibility to levofloxacin, thus reclassifying the condition as multidrug-resistant tuberculosis (MDR-TB). However, by the time these patients were transferred to our hospital and began MDR-TB treatment, they had already developed resistance to levofloxacin, escalating their condition to pre-XDR TB. These cases underscore the importance of rapid access to comprehensive DST upon the identification of rifampicin resistance and adherence to established clinical guidelines.

The impact of spousal behavior changes on smoking, drinking and physical activity: The longitudinal survey of middle-aged and elderly persons in Japan.

The purpose of this study is to assess how one spouse's behavior change can influence their partner's successful behavior changes in smoking, drinking and physical activity. We used data from 10-wave prospective annual surveys of 9417 married couples (discrete-time person-years = 118,876) aged 50-59 years in the Longitudinal Survey of Middle-aged and Elderly Persons in Japan. A logistic generalized estimating equation model with discrete-time design was used among individuals who smoked at baseline to examine the impact of their spouse's health behaviors (i.e. quit smoking, stable non-smoker, or started smoking in reference to stable smoker) on changes in their own behavior (quitting smoking) which lasted one year or more. Similarly, reducing alcohol intake and starting physical activity were individually analyzed. Partners of spouses who had quit smoking had higher odds of quitting smoking themselves than partners of spouses who were stable smokers. The multivariable odds ratios[95%CI] in men and women were 1.94[1.23-3.07] and 2.89[1.81-4.52]. An association was found in partners of spouses who had been stable non-smokers (OR:1.64[1.33-2.03] and 2.20[1.66-2.94]), but not after spouses had started smoking (OR:1.29[0.71-2.36] and 1.27[0.54-2.99]). Similar associations were found for reducing alcohol intake and starting physical activity although for physical activity, the association was still found after the spouse had become physically inactive. Couples affect each other's health behaviors. Both male and female participants had higher odds of adopting positive health behavior changes if these changes had previously been made by their spouse.

Seasonal shift in epidemics of respiratory syncytial virus infection in Japan.

In Japan, respiratory syncytial virus (RSV) infection generally has occurred during autumn and winter. However, a possible change in the seasonal trend of RSV infection has been observed recently. The current study was conducted to determine whether the epidemic season of RSV infection in Japan has indeed changed significantly. We used expectation-based Poisson scan statistics to detect periods with high weekly reported RSV cases (epidemic cluster), and the epidemic clusters were detected between September and December in the 2012-2016 seasons while those were detected between July and October in the 2017-2019 seasons. Non-linear and linear ordinary least squares regression models were built to evaluate whether there is a difference in year trend in the epidemic seasonality, and the epidemic season was shifted to earlier in the year in 2017-2019 compared to that in 2012-2016. Although the reason for the shift is unclear, this information may help in clinical practice and public health.

Effectiveness of monthly and bimonthly follow-up of patients with well-controlled type 2 diabetes: a propensity score matched cohort study.

BACKGROUND: On average, patients in Japan with type 2 diabetes mellitus have a clinical consultation every month, although evidence for a favorable follow-up interval is lacking. This study investigated whether the follow-up interval can be extended by comparing the clinical outcomes and cost for monthly versus bimonthly follow-up of patients with well-controlled diabetes mellitus. METHODS: We combined administrative claims data from the National Health Insurance and the Health Checkups Program data of Tsu city, Japan between 2011 and 2014 to conduct a retrospective cohort study of patients with well-controlled type 2 diabetes mellitus. Propensity scores were used to assemble a matched-pairs cohort from patients who had monthly and bimonthly follow-up. Equivalence between two groups was assessed by designating the proportion of patients who maintained good control of their diabetes in the subsequent year as a primary outcome. The proportion achieving target blood pressure and lipid levels, favorable lifestyle, and annual cost were compared as secondary outcomes. RESULTS: Of 12,145 participants, 693 with monthly follow-up and 693 with bimonthly follow-up were matched using propensity scores. In the monthly follow-up group 654 (94.4%) remained under good diabetic control, versus 658 (95.0%) in the bimonthly group (difference: 0.6%; 95% confidence interval: - 1.8 to 2.9%). All secondary outcomes were equivalent for the monthly and bimonthly follow-up groups except the proportion achieving target blood pressure, the proportion engaging in regular exercise, and annual cost. CONCLUSIONS: For patients with well-controlled diabetes mellitus, although frequent follow-up by a physician does not affect the control of blood glucose level in the subsequent year, the annual treatment cost becomes much higher. We suggest that patients with well-controlled diabetes can be followed up less often.

Activated protein C plays no major roles in the inhibition of coagulation or increased fibrinolysis in acute coagulopathy of trauma-shock: a systematic review.

BACKGROUND: The pathophysiological mechanisms of acute coagulopathy of trauma-shock (ACOTS) are reported to include activated protein C-mediated suppression of thrombin generation via the proteolytic inactivation of activated Factor V (FVa) and FVIIIa; an increased fibrinolysis via neutralization of plasminogen activator inhibitor-1 (PAI-1) by activated protein C. The aims of this study are to review the evidences for the role of activated protein C in thrombin generation and fibrinolysis and to validate the diagnosis of ACOTS based on the activated protein C dynamics. METHODS: We conducted systematic literature search (2007-2017) using PubMed, the Cochrane Database of Systematic Reviews (CDSR), and the Cochrane Central Register of Controlled Trials (CENTRAL). Clinical studies on trauma that measured activated protein C or the circulating levels of activated protein C-related coagulation and fibrinolysis markers were included in our study. RESULTS: Out of 7613 studies, 17 clinical studies met the inclusion criteria. The levels of activated protein C in ACOTS were inconsistently decreased, showed no change, or were increased in comparison to the control groups. Irrespective of the activated protein C levels, thrombin generation was always preserved or highly elevated. There was no report on the activated protein C-mediated neutralization of PAI-1 with increased fibrinolysis. No included studies used unified diagnostic criteria to diagnose ACOTS and those studies also used different terms to refer to the condition known as ACOTS. CONCLUSIONS: None of the studies showed direct cause and effect relationships between activated protein C and the suppression of coagulation and increased fibrinolysis. No definitive diagnostic criteria or unified terminology have been established for ACOTS based on the activated protein C dynamics.

The roles of activated protein C in experimental trauma models.

Trauma-induced coagulopathy is classified into primary and secondary coagulopathy, with the former elicited by trauma and traumatic shock itself and the latter being acquired coagulopathy induced by anemia, hypothermia, acidosis, and dilution. Primary coagulopathy consists of disseminated intravascular coagulation and acute coagulopathy of trauma shock (ACOTS). The pathophysiology of ACOTS is the suppression of thrombin generation and neutralization of plasminogen activator inhibitor-1 mediated by activated protein C that leads to hypocoagulation and hyperfibrinolysis in the circulation. This review tried to clarify the validity of activated protein C hypothesis that constitutes the main pathophysiology of the ACOTS in experimental trauma models.

A comparison of the results of prospective and retrospective cohort studies in the field of digestive surgery.

PURPOSE: We compared the results of prospective and retrospective cohort studies in the field of digestive surgery to clarify whether the results of prospective cohort studies were more similar to those of randomized controlled trials (RCTs). METHODS: We conducted a secondary analysis of the results to compare the results of RCTs with those of cohort studies in meta-analyses of 18 digestive surgical topics. The data from the prospective and retrospective cohort studies were combined. The summary estimates of each design were compared with those of RCTs. We used the Z score to investigate discrepancies. RESULTS: Twenty-nine outcomes of 11 topics were investigated in 289 cohort studies (prospective, n = 69; retrospective, n = 220). These were compared with the outcomes of 123 RCTs. In comparison to retrospective studies, the summary estimates of the prospective cohort studies were more similar to those of the RCTs [19/29 (prospective) vs. 10/29 (retrospective), P = 0.035). Five of the 29 outcomes of prospective studies and 6 of 29 outcomes of retrospective studies (P = 0.99) showed significant discrepancies in comparison to RCTs. CONCLUSIONS: In the digestive surgical field, the results of prospective cohort studies tended to be more similar to those of RCTs than retrospective studies; however, there were no significant discrepancies between the two types of cohort study.

Evidence of surgical outcomes fluctuates over time: results from a cumulative meta-analysis of laparoscopic versus open appendectomy for acute appendicitis.

BACKGROUND: In surgical trials, complex variables such as equipment development and surgeons' learning curve are involved. The evidence obtained in these trials can thus fluctuate over time. We explored the stability of the evidence obtained during surgery by conducting a cumulative meta-analysis of randomized controlled trials for open and laparoscopic appendectomy. METHODS: We conducted a cumulative meta-analysis of randomized controlled trials comparing laparoscopic appendectomy with open appendectomy for acute appendicitis, a topic with the greatest number of trials in the gastroenterological surgical field. We searched the MEDLINE (PubMed), EMBASE, and CINAHL databases up to September 2014 and reviewed the bibliographies. Outcomes were the incidence of intra-abdominal abscess, incidence of wound infection, operative time, and length of hospital stay. We used the 95 % confidence interval (95 % CI) of effect size for the significance test. RESULTS: Sixty-four trials were included in this analysis. Of the 51 trials addressing intra-abdominal abscesses, our cumulative meta-analysis of trials published up to and including 2001 demonstrated statistical significance in favor of open appendectomy (cumulative odds ratio [OR] 2.35, 95 % CI 1.30-4.25). The effect size in favor of open procedures began to disappear after 2001, leading to an insignificant result with an overall cumulative OR of 1.32 (95 % CI 0.84-2.10) when laparoscopic appendectomy was compared with open appendectomy. CONCLUSIONS: The evidence regarding treatment effectiveness changed over time, after treatment effectiveness became significant in trials comparing laparoscopic and open appendectomy. Observing only the 95 % confidence interval of effect size from a meta-analysis may not provide conclusive results.

Aortic coarctation repair in neonates with intracardiac defects: the importance of preservation of the lesser curvature of the aortic arch.

BACKGROUND AND AIM: The aim of this study was to evaluate the mid-term outcomes of a strategy for repair of coarctation of the aorta (CoA) and hypoplastic aortic arch (HAA) with a modified, extended end-to-end repair that preserves the lesser curvature of the aortic arch in neonates with intracardiac defects. METHODS: We studied 21 neonates who underwent CoA repair and remote intracardiac repair (2000-2013). Fifteen patients had HAA, and six patients had no HAA. Follow-up ranged from 0.4 to 12.8 years (median, 7.5 years), and all patients underwent cardiac catheterization and blood pressure measurement in both the arms and legs. RESULTS: The overall median age at the time of CoA repair was seven days and the median age at the time of intracardiac defect repair was 18.6 months. There were no hospital deaths and one case had recoarctation (4.8%). The overall mean pressure gradient at the latest follow-up was 3.4 ± 5.7 mmHg. Critical deformation of arch geometry was not found. No patient had hypertension or an abnormal arm-leg gradient. There was no difference in the cardiac catheterization data or blood pressure between patients with and without HAA. CONCLUSIONS: A modified, extended end-to-end repair for CoA and HAA resulted in a low rate of recoarctation, no operative mortality, maintenance of a smooth rounded arch, and normal blood pressures in the arms and legs during mid-term follow-up. These results suggest that this technique may be acceptable for repair of CoA and HAA in neonates with intracardiac defects.

Replacement of the extracardiac conduit for infective endocarditis after a fontan operation.

We report the management of infective endocarditis after an extracardiac Fontan operation. Obstruction of the infected conduit and the associated pulmonary arterial embolism led to failure of the Fontan circulation. This was managed by completely removing both the infected conduit and emboli and replacing the conduit.

Political Party Affiliation and COVID-19 Vaccination Status in Japan, 2022.

INTRODUCTION: An association has been reported between political affiliations and vaccination worldwide. In Japan, a significant proportion of the population are non-partisans, and major political parties advocate COVID-19 vaccination. The association between supporting political parties and COVID-19 vaccination coverage in Japan remains unclear. This study aims to investigate the relationship between political party affiliation and COVID-19 vaccination status in Japan.  Methods: This study utilized data from large-scale nationwide internet surveys conducted in Japan in 2022, with a sample size of 21,162 participants. The surveys collected information on participants' COVID-19 vaccination status and political party affiliation. The political parties included in the analysis were the Liberal Democratic Party, the Constitutional Democratic Party, the Komeito, the Japanese Communist Party, the Japan Innovation Party (Nippon Ishin no Kai), and the Reiwa Shinsengumi, as well as non-partisans. Logistic regression analysis was performed to examine the relationship between political partisanship and COVID-19 vaccine status. The analysis controlled for potential confounding variables such as age, gender, socioeconomic status, and geographic location. RESULTS: The odds of being unvaccinated were lower for supporters of large political groups (e.g. Liberal Democratic Party {OR 0.6; 95% CI, 0.5-0.7}), while higher for small political groups (e.g. Reiwa Shinsengumi {OR 2.6; 95% CI, 1.9-3.6}), in comparison with non-partisan. CONCLUSION: Political affiliation may be associated with vaccination disparities in Japan. Supporters of minor parties were more likely to be unvaccinated than those of the larger parties. However, this study has several limitations, including self-reporting bias and selection bias due to the Internet survey methodology.

Anatomical repair of aortopulmonary window with anomalous origin of the right coronary artery from the pulmonary artery.

Aortopulmonary window (APW) with an anomalous origin of a coronary artery is extremely rare. We report surgical management of a four-week-old infant with the association of a distal type of APW and an anomalous origin of the right coronary artery (RCA) from the pulmonary artery. Complete anatomical correction comprising division of the great arteries and transferring the RCA as an autologous flap to the aortic defect was successfully performed.

Association between social isolation and loneliness with COVID-19 vaccine uptake in Japan: a nationwide cross-sectional internet survey.

OBJECTIVES: We examined the association between social isolation and loneliness, increasingly recognised but neglected social determinants of health, with being unvaccinated against COVID-19. DESIGN: This was a cross-sectional study. SETTING AND PARTICIPANTS: A representative cohort of 22 756 individuals (aged 15-81 years) from the general Japanese population who responded to both the Japan COVID-19 and Society Internet Survey 2021 and Japan Society and New Tobacco Internet Survey 2022. PRIMARY AND SECONDARY OUTCOME MEASURES: We calculated the ORs of remaining unvaccinated against COVID-19 in 2022, attributable to social isolation as assessed by the Lubben Social Network Scale, or loneliness as evaluated by the University of California, Los Angeles Loneliness Scale version 3. Reasons for abstaining from vaccination were solicited from the unvaccinated respondents. A multivariable logistic regression model was conducted with adjustments for demographic variables. Propensity score-matched comparisons were conducted as part of the sensitivity analysis. RESULTS: Individuals with social isolation were more likely to be unvaccinated (OR 1.48, 95% CI 1.37 to 1.60), while individuals with loneliness were not (OR 0.96, 95% CI 0.88 to 1.05). Socially isolated individuals were significantly less likely to receive information from people who had been vaccinated (11% vs 15%) and less likely not to trust the vaccine approval process (19% vs 27%) compared with those who were not socially isolated. CONCLUSIONS: Despite not harbouring negative perceptions of the vaccine, socially isolated individuals exhibited lower rates of COVID-19 vaccination. Socially isolated individuals are important targets to reach to increase the number of vaccinated individuals.

Predictors of hospital mortality and multidrug-resistant pathogens in hospitalized pneumonia patients residing in the community.

Background and objective: The 2019 ATS/ADSA guidelines for adult community-acquired pneumonia (CAP) eliminated healthcare-associated pneumonia (HCAP) and considered it to be a form of CAP. This concept, however, was based on studies with relatively small sample sizes. Methods: We investigated the risk factors of 30-day mortality, and methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa infections in patients with pneumonia coming from the community using the Diagnosis Procedure Combination database, a nationwide discharge database of acute care hospitals. Furthermore, we compared these factors between CAP and HCAP. Results: A total of 272,337 patients aged ≥20 years with pneumonia were grouped into 145,082 CAP patients and 127,255 HCAP patients. The 30-day mortality rate (8.9 % vs.3.3 %), MRSA infection (2.4 % vs. 1.4 %), and Pseudomonas aeruginosa infection (1.6 % vs. 1.0 %) were significantly higher in HCAP than in CAP patients. Multivariable logistic regression analysis showed that 12 of 13 identified predictors of mortality (i.e., high age, male, underweight, non-ambulatory status, bedsore, dehydration, respiratory failure, consciousness disturbance, hypotension, admitted in critical care, comorbidity of heart failure, and chronic obstructive pulmonary disease) were identical in CAP and HCAP patients. Similarly, five of six distinct risk factors for MRSA infection, and three of three for Pseudomonas aeruginosa infection were identical between the patients. Conclusion: The risk factors for mortality and MRSA or Pseudomonas aeruginosa infection were almost identical in patients with CAP and HCAP. The assessment of individual risk factors for mortality and MRSA or Pseudomonas aeruginosa infection in CAP and abandoning categorization as HCAP can improve and simplify empiric therapy.

Exploring the threshold for the start of respiratory syncytial virus infection epidemic season using sentinel surveillance data in Japan.

Introduction: An unusual seasonality of respiratory syncytial virus (RSV) infection in Japan is observed in recent years after 2017, becoming challenging to prepare for: a seasonal shift from autumn-winter to summer-autumn in 2017-2019, no major epidemic in 2020, and an unusually high number of cases reported in 2021. Methods: To early detect the start-timing of epidemic season, we explored the reference threshold for the start-timing of the epidemic period based on the number of cases per sentinel (CPS, a widely used indicator in Japanese surveillance system), using a relative operating characteristic curve analysis (with the epidemic period defined by effective reproduction number). Results: The reference values of Tokyo, Kanagawa, Osaka, and Aichi Prefectures were 0.41, 0.39, 0.42, and 0.24, respectively. Discussion: The reference CPS value could be a valuable indicator for detecting the RSV epidemic and may contribute to the planned introduction of monoclonal antibody against RSV to prevent severe outcomes.

Associations between the perception of risk in radiation exposure and changes in smoking and drinking status after a disaster: The Fukushima Health Management Survey.

The risk for people evacuated from Fukushima following the Great East Japan Earthquake of developing cancer from radiation exposure may be lower than that associated with smoking and alcohol drinking. However, the perception of those risks may change risk-related behavior. Therefore, we investigated whether the perceived risk of radiation exposure was associated with the initiation and/or cessation of smoking and of drinking alcohol following the disaster. Participants were 82,197 people aged ≥20 years who completed the Fukushima Health Management Study survey. A multivariable logistic regression model, with adjusted odds ratios (AORs) and 95 % confidence intervals (CIs), was used to calculate the risk of (1) starting smoking (or drinking) among people who did not smoke (or drink) before the earthquake, and (2) quitting smoking (or drinking) among people who smoked (or drank) before the earthquake; the main factor was perceived risk of developing cancer from radiation. The AORs for starting smoking among participants who perceived radiation exposure risks as unlikely, likely, and very likely, compared with very unlikely, were 0.96(0.78-1.18), 1.17(0.95-1.45), and 1.69(1.39-2.06), respectively (Trend p < 0.01). The corresponding ORs for starting drinking were 1.05 (0.95-1.16), 1.17(1.06-01.30), and 1.38(1.25-1.52), respectively (Trend p < 0.01). The AORs for quitting smoking were 0.90(0.82-0.98), 0.81(0.73-0.90), and 0.75(0.68-0.83), respectively (Trend p < 0.01). The same association was not found among alcohol quitters. In Fukushima, people who perceived greater risk of developing cancer from radiation exposure had higher odds of starting smoking and drinking alcohol, which, ironically, increases the risk of developing cancer.

Singing Is a Risk Factor for Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Case-Control Study of Karaoke-Related Coronavirus Disease 2019 Outbreaks in 2 Cities in Hokkaido, Japan, Linked by Whole Genome Analysis.

Background: Singing in an indoor space may increase the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a case-control study of karaoke-related coronavirus disease 2019 (COVID-19) outbreaks to reveal the risk factors for SARS-CoV-2 infection among individuals who participate in karaoke. Methods: Cases were defined as people who enjoyed karaoke at a bar and who tested positive for SARS-CoV-2 by reverse-transcription polymerase chain reaction between 16 May and 3 July 2020. Controls were defined as people who enjoyed karaoke at the same bar during the same period as the cases and tested negative. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. ORs of key variables adjusted for each other were also estimated (aOR). Results: We identified 81 cases, the majority of whom were active elderly individuals (median age, 75 years). Six cases died (case fatality ratio, 7%). Among the cases, 68 (84%) were guests, 18 of whom had visited ≧2 karaoke bars. A genome analysis conducted in 30 cases showed 6 types of isolates within 4 single-nucleotide variation difference. The case-control study revealed that singing (aOR, 11.0 [95% CI, 1.2-101.0]), not wearing a mask (aOR, 3.7 [95% CI, 1.2-11.2]), and additional hour spent per visit (aOR, 1.7 [95% CI, 1.1-2.7]) were associated with COVID-19 infection. Conclusions: A karaoke-related COVID-19 outbreak that occurred in 2 different cities was confirmed by the results of genome analysis. Singing in less-ventilated, indoor and crowded environments increases the risk of acquiring SARS-CoV-2 infection. Wearing a mask and staying for only a short time can reduce the risk of infection during karaoke.

Enhanced event-based surveillance for imported diseases during the Tokyo 2020 Olympic and Paralympic Games.

In 2021, the National Institute of Infectious Diseases, Japan, undertook enhanced event-based surveillance (EBS) for infectious diseases occurring overseas that have potential for importation (excluding coronavirus disease 2019 [COVID-19]) for the Tokyo 2020 Olympic and Paralympic Summer Games (the Games). The pre-existing EBS system was enhanced using the World Health Organization Epidemic Intelligence from Open Sources system and the BlueDot Epidemic Intelligence platform. The enhanced EBS before and during the Games did not detect any major public health event that would warrant action for the Games. However, information from multiple sources helped us identify events, characterize risk and improve confidence in risk assessment. The collaboration also reduced the surveillance workload of the host country, while ensuring the quality of surveillance, even during the COVID-19 pandemic.

Clinical practice guidelines for the management of liver metastases from extrahepatic primary cancers 2021.

BACKGROUND: Hepatectomy is standard treatment for colorectal liver metastases; however, it is unclear whether liver metastases from other primary cancers should be resected or not. The Japanese Society of Hepato-Biliary-Pancreatic Surgery therefore created clinical practice guidelines for the management of metastatic liver tumors. METHODS: Eight primary diseases were selected based on the number of hepatectomies performed for each malignancy per year. Clinical questions were structured in the population, intervention, comparison, and outcomes (PICO) format. Systematic reviews were performed, and the strength of recommendations and the level of quality of evidence for each clinical question were discussed and determined. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations. RESULTS: The eight primary sites were grouped into five categories based on suggested indications for hepatectomy and consensus of the guidelines committee. Fourteen clinical questions were devised, covering five topics: (1) diagnosis, (2) operative treatment, (3) ablation therapy, (4) the eight primary diseases, and (5) systemic therapies. The grade of recommendation was strong for one clinical question and weak for the other 13 clinical questions. The quality of the evidence was moderate for two questions, low for 10, and very low for two. A flowchart was made to summarize the outcomes of the guidelines for the indications of hepatectomy and systemic therapy. CONCLUSIONS: These guidelines were developed to provide useful information based on evidence in the published literature for the clinical management of liver metastases, and they could be helpful for conducting future clinical trials to provide higher-quality evidence.

Habitual tub bathing and risks of incident coronary heart disease and stroke.

OBJECTIVE: Tub bathing is considered to have a preventive effect against cardiovascular disease (CVD) by improving haemodynamic function. However, no prospective studies have investigated the long-term effects of tub bathing with regard to CVD risk. METHODS: A total of 30 076 participants aged 40-59 years with no history of CVD or cancer were followed up from 1990 to 2009. Participants were classified by bathing frequency: zero to two times/week, three to four times/week and almost every day. The HRs of incident CVD were estimated using Cox proportional hazards models after adjusting for traditional CVD risk factors and selected dietary factors. RESULTS: During 538 373 person-years of follow-up, we documented a total of 2097 incident cases of CVD, comprising 328 coronary heart diseases (CHDs) (275 myocardial infarctions and 53 sudden cardiac deaths) and 1769 strokes (991 cerebral infarctions, 510 intracerebral haemorrhages, 255 subarachnoid haemorrhages and 13 unclassified strokes). The multivariable HRs (95% CIs) for almost daily or every day versus zero to two times/week were 0.72 (0.62 to 0.84, trend p<0.001) for total CVD; 0.65 (0.45 to 0.94, trend p=0.065) for CHD; 0.74 (0.62 to 0.87, trend p=0.005) for total stroke; 0.77 (0.62 to 0.97, trend p=0.467) for cerebral infarction; and 0.54 (0.40 to 0.73, trend p<0.001) for intracerebral haemorrhage. No associations were observed between tub bathing frequency and risk of sudden cardiac death or subarachnoid haemorrhage. CONCLUSION: The frequency of tub bathing was inversely associated with the risk of CVD among middle-aged Japanese.