Longitudinal antibody dynamics after COVID-19 vaccine boosters based on prior infection status and booster doses.

Global concern over COVID-19 vaccine distribution disparities highlights the need for strategic booster shots. We explored longitudinal antibody responses post-booster during the Omicron wave in a Japanese cohort, emphasizing prior infection and booster doses. This prospective cohort study included 1763 participants aged 18 years and older with at least three vaccine doses (7376 datapoints). Antibody levels were measured every 2 months. We modeled temporal declines in antibody levels after COVID-19 vaccine boosters according to prior infection status and booster doses using a Bayesian linear mixed-effects interval-censored model, considering age, sex, underlying conditions, and lifestyle. Prior infection enhanced post-booster immunity (posterior median 0.346, 95% credible interval [CrI] 0.335-0.355), maintaining antibody levels (posterior median 0.021; 95% CrI 0.019-0.023) over 1 year, in contrast to uninfected individuals whose levels had waned by 8 months post-vaccination. Each additional booster was correlated with higher baseline antibody levels and slower declines, comparing after the third dose. Female sex, older age, immunosuppressive status, and smoking history were associated with lower baseline post-vaccination antibodies, but not associated with decline rates except for older age in the main model. Prior infection status and tailored, efficient, personalized booster strategies are crucial, considering sex, age, health conditions, and lifestyle.

Complementary and Alternative Medicine Use, Cancer Screening, and Medical Checkups in Japan from 2001 to 2013: A Repeated Cross-Sectional Study.

Introduction: The association between complementary and alternative medicine (CAM) use and other health-related behaviors is an important issue. A previous study reported that complementary medicine use is related to greater use of cancer screening, whereas alternative medicine use is related to lower use of cancer screening. Given the sparse evidence from Japan, we aimed to examine the association of CAM use with cancer screening and medical checkups. We used a repeated cross-sectional survey of a nationally representative sample of Japanese people and conducted age-period-cohort analysis. Methods: The study population was 68,217 of 83,827 individuals observed from 2001 to 2013 who received cancer screening. CAM users were defined as individuals who received acupuncture, moxibustion, anma/massage/shiatsu, or judo therapy for their most worrisome symptom. The outcomes of interest were receiving stomach, lung, colorectal, uterine, and breast cancer screenings and medical checkups. Using crossclassified multilevel logistic regression models, we estimated odds ratios (ORs) and 95% credible intervals (CIs) for cancer screening and medical checkups. Results: For CAM users of complementary medicine, the adjusted ORs for stomach, lung, and colorectal cancer screening were 1.40 (95% CI: 1.35-1.44), 1.37 (95% CI: 1.34-1.40), and 1.52 (95% CI: 1.49-1.54), respectively. We found similar results for uterine and breast cancer screening, and medical checkups. Conclusions: Irrespective of whether they use CAM, CAM users in Japan tend to receive a variety of cancer screenings and medical checkups.

Staged repair for complete atrioventricular septal defect in patients weighing less than 4.0 kg.

OBJECTIVE: This study compared the mortality, left atrioventricular valve-related reoperation, and left atrioventricular valve competence in symptomatic neonates and small infants who underwent staged repair incorporating pulmonary artery banding or primary repair for complete atrioventricular septal defect. METHODS: Patients weighing less than 4.0 kg at the time of undergoing staged (n = 37) or primary (n = 23) repair for balanced complete atrioventricular septal defect between 1999 and 2022 were reviewed. The mean follow-up period was 9.1 years. Freedom from moderate or greater left atrioventricular valve regurgitation was estimated with the Kaplan-Meier method. RESULTS: The staged group included smaller children (median weight, 2.9 vs 3.7 kg) and a higher proportion of neonates (41% vs 4%). All patients in the staged group survived pulmonary artery banding and underwent intracardiac repair (median weight, 6.8 kg). After pulmonary artery banding, the severity of left atrioventricular valve regurgitation improved in 10 of 12 patients (83%) without left atrioventricular valve anomaly who had mild or greater left atrioventricular valve regurgitation and a left atrioventricular valve Z score greater than 0. Although survival and freedom from left atrioventricular valve-related reoperation at 15 years (P = .195 and .602, respectively) were comparable between the groups, freedom from moderate or greater left atrioventricular valve regurgitation at 15 years was higher in the staged group (P = .026). CONCLUSIONS: Compared with primary repair, staged repair for complete atrioventricular septal defect in children weighing less than 4.0 kg resulted in comparable survival and reoperation rates and better left atrioventricular valve competence. Pulmonary artery banding may mitigate secondary left atrioventricular valve regurgitation unless a structural valve abnormality exists. Selective deferred intracardiac repair beyond the neonatal and small-infancy period may still play an important role in low-weight patients.

Effect of stomach inflation during cardiopulmonary resuscitation on return of spontaneous circulation in out-of-hospital cardiac arrest patients: A retrospective observational study.

BACKGROUND: Gastric inflation caused by excessive ventilation is a common complication of cardiopulmonary resuscitation. Gastric inflation may further compromise ventilation via increases in intrathoracic pressure, leading to decreased venous return and cardiac output, which may impair out-of-hospital cardiac arrest (OHCA) outcomes. The purpose of this study was to measure the gastric volume of OHCA patients using computed tomography (CT) scan images and evaluate the effect of gastric inflation on return of spontaneous circulation (ROSC). METHODS: In this single-center, retrospective, observational study, CT scan was conducted after ROSC or immediately after death. Total gastric volume was measured. Primary outcome was ROSC. Achievement of ROSC was compared in the gastric distention group and the no gastric distention group; gastric distension was defined as total gastric volume in the ≥75th percentile. Additionally, factors associated with gastric distention were examined. RESULTS: A total of 446 cases were enrolled in the study; 120 cases (27%) achieved ROSC. The median gastric volume was 400 ml for all OHCA subjects; 1068 ml in gastric distention group vs. 287 ml in no gastric distention group. There was no difference in ROSC between the groups (27/112 [24.1%] vs. 93/334 [27.8%], p = 0.440). Gastric distention did not have a significant impact, even after adjustments (adjusted odds ratio 0.73, 95% confidence interval [0.42-1.29]). Increased gastric volume was associated with longer emergency medical service activity time. CONCLUSIONS: We observed a median gastric volume of 400 ml in patients after OHCA resuscitation. In our setting, gastric distention did not prevent ROSC.

A population-based longitudinal study on glycated hemoglobin levels and new-onset chronic kidney disease among non-diabetic Japanese adults.

Chronic kidney disease (CKD) is a major global public health problem. Recent studies reported that diabetes and prediabetes are risk factors for developing CKD; however, the exact glycated hemoglobin (HbA1c) cut-off value for prediabetes remains controversial. In this study, we aimed to examine the relationship between HbA1c levels and subsequent CKD development in greater detail than previous studies. Longitudinal data of annual checkups of 7176 Japanese non-diabetic people (male: 40.4%) from 1998 to 2022 was analyzed. HbA1c values were categorized into < 5.0%, 5.0-5.4%, 5.5-5.9%, and 6.0-6.4%. CKD was defined as an estimated glomerular filtration rate < 60 ml/min/1.73 m2. The descriptive statistics at study entry showed that higher HbA1c values were associated with male, older, overweight or obese, hypertensive, or dyslipidemic people. During a mean follow-up of 7.75 person-years, 2374 participants (male: 40.0%) developed CKD. The Weibull accelerated failure time model was selected because the proportional hazards assumption was violated. The adjusted time ratios of developing CKD for HbA1c levels of 5.5-5.9% and 6.0-6.4% compared with 5.0-5.4% were 0.97 (95% confidence interval: 0.92-1.03) and 1.01 (95% confidence interval: 0.90-1.13), respectively. There was no association between HbA1c in the prediabetic range and subsequent CKD development.

Efficacy of telerehabilitation for patients after hip fracture surgery: A systematic review and meta-analysis.

INTRODUCTION: This study aimed to determine the efficacy of telerehabilitation for patients after hip fracture surgery through a systematic review and meta-analysis. METHODS: Eight electronic databases were searched in August 2022. The primary outcomes were mobility outcomes, activities of daily living (ADL) outcomes, and all adverse events, whereas the secondary outcomes were pain, health-related quality of life, and fall efficacy scale score. RESULTS: Seven randomized controlled trials were eligible for this study. The evidence regarding the effect of telerehabilitation on mobility outcomes (standardized mean difference (SMD): 0.05, 95% confidence interval (CI): -0.39 to 0.48) and all adverse events (risk ratio: 1.14, 95% CI: 0.62 to 2.21) was very uncertain. A clinically irrelevant but significant mean difference (MD) in ADL outcomes was found (MD: 4.82, 95% CI: 2.63 to 7.01). Telerehabilitation may result in a slight increase in fall efficacy scale score (SMD: 0.26, 95% CI: -0.02 to 0.54) and little to no difference in pain (MD: -1.0, 95% CI: -18.31 to 16.31). CONCLUSIONS: The efficacy of telerehabilitation for patients after hip fracture surgery was uncertain with respect to the mobility outcomes, all adverse events, and pain, with no clinically meaningful differences in ADL outcomes. Telerehabilitation may be necessary to be considered for patients after hip fracture surgery to improve their confidence in their ability to perform daily activities without falling. Therefore, medical staff may consider telerehabilitation for hip fractures.

Early childhood exposure to maternal smoking and obesity: A nationwide longitudinal survey in Japan.

Involuntary exposure to tobacco smoke is suspected to be one of the risks factors that are associated with obesity in children. The purpose of this study was to examine the relationship between early childhood exposure to tobacco smoke and the risk of obesity and overweight in Japan. This study utilized a nationwide, population-based longitudinal survey. The participants were restricted to 32 081 children who had available information on maternal smoking history as well as childhood height and weight. We conducted a binomial log-linear regression analysis with children of non-smoking mothers as the reference group. The children with mothers who were smokers had a higher risk of developing obesity or being overweight compared to the children with mothers who were nonsmokers. The risk ratios were 1.20 (95% confidence interval [CI]: 1.09-1.32) for overweight and 1.17 (95% CI: 0.95-1.44) for obesity. Early exposure to maternal smoking increases the risk of being overweight and having obesity during childhood. The increased risk is more pronounced among children with mothers, smoked heavily, or parents, who were smokers.

Frailty and all-cause and cause-specific mortality in Japan.

BACKGROUND: In aging societies, there is an increasing focus on the concept of frailty. However, there is no consistent means to assess this concept. We assessed frailty using the Kihon Checklist (KCL), which is widely used in Japan, and examined the association between frailty and all-cause and cause-specific mortality in Japan, the most aged society in the world. METHODS: This was a retrospective cohort study, and we analyzed 43,312 participants aged ≥ 65 years who were enrolled in basic health checkups in Okayama City, Japan. We defined the frailty status of the participants using the KCL. To assess the association of frailty status with all-cause and cause-specific mortality, we used cause-specific Cox proportional hazard models to estimate hazard ratios (HRs), adjusting for individual potential confounders. Mean follow-up time was 9.3 years. RESULTS: The fully adjusted HR for all-cause mortality was 1.34 (95% confidence interval [CI]: 1.27-1.41) for the prefrail group and 2.22 (95% CI: 2.11-2.33) for the frail group. A similar pattern was observed for cardiovascular disease, respiratory disease, and cancer mortality. Younger people (65-74 years) and women tended to have higher effect estimates than older people (≥ 75 years) and men. CONCLUSION: Prefrailty and frailty can increase the risk of both all-cause and cause-specific mortality. Our study suggests that to support frail patients, it could be effective to focus on the prevention and management of cardiovascular and respiratory disease, and that the KCL may be useful as a method of screening for frailty.

Breastfeeding at 6 months of age had a positive impact on overweight and obesity in Japanese adolescents at 15 years of age.

AIM: A number of studies have indicated the potential benefits that breastfeeding has on reducing childhood obesity, but few studies have evaluated the effect on adolescent obesity. We examined the association between breastfeeding and overweight or obesity at 15 years of age using data from a large nationwide longitudinal study launched by the Japanese Government in 2001. METHODS: We analysed data for 26 164 participants with known infant feeding practices at 6 months of age, namely the duration of breastfeeding or formula feeding. Overweight or obesity at 15 years of age were calculated based on the subject's self-reported height and weight. Multinomial logistic regression analysis adjusted the data for child factors, namely sex, siblings, birth weight and physical activity clubs and the maternal factors of age, educational attainment and smoking status. RESULTS: Formula feeding was associated with an increased risk of overweight or obesity at 15 years of age. The adjusted odds ratios (95% confidence intervals) were 0.99 (0.89-1.09) for partial breastfeeding and 1.23 (1.02-1.48) for formula feeding, when exclusive breastfeeding was the reference category. CONCLUSION: Breastfeeding during infancy had potential benefits for overweight or obesity among 15-year-old adolescents. Our results provide further evidence of the importance of breastfeeding.

Neonatal sepsis and Kawasaki disease.

The purpose of this study is to clarify the relationship between neonatal sepsis and future development of Kawasaki disease (KD). We analyzed data from the National Hospital Organization Neonatal Intensive Care Unit (NHO-NICU) registry study in Japan. Participants in this study were children with a history of hospitalization in the NICU at the participating institutions from 2010 to 2014. A questionnaire was administered at age 3 years to obtain information about the patient's history of KD. There were 8275 infants who were eligible for this study. At 3 years of age, parents of 2161 children responded to the follow-up survey (follow-up rate, 26.1%). Multivariate logistic regression analysis adjusted for preterm birth, sex, use of antibiotics in the NICU, parity, and maternal smoking showed that children with neonatal sepsis were more likely to have a history of KD at 3 years of age (adjusted odds ratio [aOR]: 11.67, 95% confidence interval [CI]: 2.84-47.96). CONCLUSIONS: Among infants admitted to the NICU, neonatal sepsis might be associated with development of KD later in life. Further large studies are needed to elucidate the relationship between neonatal infections and KD development. WHAT IS KNOWN: • Preterm birth is known to be a risk factor for Kawasaki disease. •It is not yet known which factors related to preterm birth increase the risk of developing Kawasaki disease. WHAT IS NEW: •Neonatal sepsis is associated with an increased risk of subsequent development of Kawasaki disease. •Antibiotic use in the neonatal intensive care unit may also be an independent risk factor for subsequent development of Kawasaki disease.

Standardized incidence ratios of malignant neoplasms among patients with pneumoconiosis.

BACKGROUND: Patients with pneumoconiosis, such as silicosis and asbestosis, have a high risk of lung cancer. However, whether these patients are at high risk for neoplasms other than lung cancer and mesothelioma remains inconclusive. AIMS: To examine whether patients with pneumoconiosis have a higher incidence of malignant neoplasms other than lung cancer. METHODS: We conducted a cohort study using the medical records of patients with pneumoconiosis who visited our two hospitals from 1 January 1991 through 31 December 2017. We identified the occurrence of malignant neoplasms and calculated the incidences and standardized incidence ratios (SIRs) compared with those of the general population. RESULTS: One hundred and seventy patients with pneumoconiosis (163 men, 7 women) including 142 patients with silicosis, 24 with asbestosis and 4 with pneumoconiosis were identified. The mean age was 66.8 years. The proportion of smokers was 79%. Forty-seven malignant neoplasms occurred. Most malignant neoplasms were lung cancer (n = 22), while some were digestive cancers such as gastric cancer (n = 9), oesophageal cancer (n = 3) and colorectal cancer (n = 3). Participants presented increased risks for lung cancer (SIR: 10.86, 95% confidence interval [CI]: 7.15-16.49), gastric cancer (SIR: 2.55, 95% CI: 1.22-5.35) and oesophageal cancer (SIR: 5.78, 95% CI: 1.86-17.92). CONCLUSIONS: Compared with the general population, patients with pneumoconiosis had an increased risk of malignant neoplasms of the digestive system in addition to lung cancer. Clinicians should consider testing for digestive system cancers as well as for lung cancers in these patients.

Long-term exposure to fine particle matter and all-cause mortality and cause-specific mortality in Japan: the JPHC Study.

BACKGROUND: Many epidemiological studies have reported the association between exposure to particulate matter and mortality, but long-term prospective studies from Asian populations are sparse. Furthermore, associations at low levels of air pollution are not well clarified. Here, we evaluated associations between long-term exposure to particulate matter <2.5 µg/m3 (PM2.5) and mortality in a Japanese cohort with a relatively low exposure level. METHODS: The Japan Public Health Center-based Prospective Study (JPHC Study) is a prospective cohort study of men and women aged 40-69 years in 1990 who were followed up through 2013 for mortality. In this cohort of 87,385 subjects who did not move residence during follow-up, average PM2.5 levels from 1998 to 2013 by linkage with 1-km2 grids of PM2.5 concentration were assigned to the residential addresses of all participants. To avoid exposure misclassification, we additionally evaluated the association between 5-year (1998-2002) cumulative exposure level and mortality during the follow-up period from 2003 to 2013 in 79,078 subjects. Cox proportional hazards models were used to calculate the association of long-term exposure to PM2.5 on mortality, with adjustment for several individual confounding factors. RESULTS: Average PM2.5 was 11.6 µg/m3. Average PM2.5 exposure was not associated with all-cause mortality or cancer and respiratory disease mortality. However, average PM2.5 was positively associated with mortality from cardiovascular disease (hazard ratio (HR) of 1.23 (95%CI=1.08-1.40) per 1-µg/m3 increase; in particular, HR in mortality from cerebrovascular disease was 1.34 (95%CI=1.11-1.61) per 1-µg/m3 increase. Additionally, these results using cumulative 5-year PM2.5 data were similar to those using average PM2.5 over 15 years. CONCLUSIONS: We found evidence for a positive association between PM2.5 exposure and mortality from cardiovascular disease in a Japanese population, even in an area with relatively low-level air pollution.

Preterm birth and Kawasaki disease: a nationwide Japanese population-based study.

BACKGROUND: Previous studies showed that preterm birth increased the risk for hospital admissions in infancy and childhood due to some acute diseases. However, the risk of preterm children developing Kawasaki disease remains unknown. In the present study, we investigate whether preterm birth increased the morbidity of Kawasaki disease. METHODS: We included 36,885 (34,880 term and 2005 preterm) children born in 2010 in Japan. We examined the association between preterm birth and hospitalization due to Kawasaki disease using a large nationwide survey in Japan. RESULTS: In log-linear regression models that were adjusted for children's characteristics (sex, singleton birth, and parity), parental characteristics (maternal age, maternal smoking, paternal smoking, maternal education, and paternal income), and residential area, preterm infants were more likely to be hospitalized due to Kawasaki disease (adjusted risk ratio: 1·55, 95% confidence interval: 1.01-2.39). We then examined whether breastfeeding status modified the potential adverse effects of preterm birth on health outcome. Preterm infants with partial breastfeeding or formula feeding had a significantly higher risk of hospitalization due to Kawasaki disease compared with term infants with exclusive breastfeeding. CONCLUSIONS: Preterm infants were at a high risk for Kawasaki disease, and exclusive breastfeeding might prevent this disease among preterm infants. IMPACT: Previous studies showed that preterm birth increased the risk for hospital admissions in infancy and childhood due to some acute diseases, however, the risk of preterm children developing Kawasaki disease remains unknown. This Japanese large population-based study showed that preterm infants were at a high risk for Kawasaki disease for the first time. Furthermore, this study suggested that exclusively breastfeeding might prevent Kawasaki disease among preterm infants.

Early childhood exposure to maternal smoking and behavioral development.

We examined the association between early childhood exposure to maternal smoking and behavioral issues at 8 years old using a large nationwide population-based longitudinal survey in Japan that began in 2001. We included 46,737 children with information about maternal smoking taken from the 6-month survey. We used logistic regression analysis to examine the hypothesis. Early childhood exposure to maternal smoking increased the risk of behavioral problems related to attention and aggressive or disruptive behavior. The adjusted odds ratios (95% confidence intervals) were 1.37 (1.22-1.54) for inability to wait their turn during play and 1.40 (1.27-1.55) for destroying toys and, compared with children of nonsmoking mothers. Children of mothers who were heavy smokers were more likely to develop behavioral problems than others. Stopping early childhood exposure to maternal exposure can protect children's neurodevelopment.

Associations between Early Surgery and Postoperative Outcomes in Elderly Patients with Distal Femur Fracture: A Retrospective Cohort Study.

Previous literature has provided conflicting results regarding the associations between early surgery and postoperative outcomes in elderly patients with distal femur fractures. Using data from the Japanese Diagnosis Procedure Combination inpatient database from April 2014 to March 2019, we identified elderly patients who underwent surgery for distal femur fracture within two days of hospital admission (early surgery group) or at three or more days after hospital admission (delayed surgery group). Of 9678 eligible patients, 1384 (14.3%) were assigned to the early surgery group. One-to-one propensity score matched analyses showed no significant difference in 30-day mortality between the early and delayed groups (0.5% versus 0.5%; risk difference, 0.0%; 95% confidence interval, -0.7% to 0.7%). Patients in the early surgery group had significantly lower proportions of the composite outcome (death or postoperative complications), shorter hospital stays, and lower total hospitalization costs than patients in the delayed surgery group. Our results showed that early surgery within two days of hospital admission for geriatric distal femur fracture was not associated with a reduction in 30-day mortality but was associated with reductions in postoperative complications and total hospitalization costs.

A Simple Prognostic Benefit Scoring System for Sarcoma Patients with Pulmonary Metastases: Sarcoma Lung Metastasis Score.

BACKGROUND: Pulmonary metastasectomy could be considered one of the treatment options for disease control in sarcoma patients with pulmonary metastases; however, there is little consensus regarding the suitable criteria for predicting the likely outcomes in these patients. The aim of this study was to establish a prognostic benefit scoring system based on preoperatively examined prognostic factors for sarcoma patients with pulmonary metastases. METHODS: This was a single-center, retrospective cohort study conducted in a cohort of 135 sarcoma patients who underwent a first pulmonary metastasectomy at Okayama University Hospital between January 2006 and December 2015. Based on the results of a multivariable logistic regression analysis performed to determine the factors influencing 3-year mortality, a Sarcoma Lung Metastasis Score was created and its correlation with 3-year survival was analyzed. RESULTS: The results of the multivariate analysis revealed significant differences in the disease-free interval (< 2 years vs. ≥ 2 years; odds ratio (OR) 4.22, 95% confidence interval (CI) 1.67-10.70), maximum tumor diameter (≥ 15 mm vs. < 15 mm; OR 3.86, 95% CI 1.75-8.52), and number of pulmonary metastases (≥ 6 vs. < 6; OR 2.65, 95% CI 1.06-6.620). The Sarcoma Lung Metastasis Score, which was defined as the total score of these three factors, reliably predicted 3-year survival (score: 0, 89.5%; 1, 63.2%; 2, 39.0%; 3, 10.5%). CONCLUSIONS: Our newly proposed simple Sarcoma Lung Metastasis Score appears to be a useful prognostic predictor for sarcoma patients with pulmonary metastases, in that it could be helpful for the selection of appropriate treatments for these patients.

Continuing surgical education of non-technical skills.

BACKGROUND: The non-technical skills for surgeons (NOTSS) system was developed as a tool to assess surgical skills for patient safety during surgery. This study aimed to develop a NOTSS-based training system for surgical trainees to acquire non-technical skills using a chest surgery scenario in a wet lab. MATERIALS AND METHODS: Trainees were categorized into three subgroups according to the years of experience as follows: Level A: 6 years or more; Level B: 3-5 years; and Level C: 1-2 years. Three stages of surgical procedure were designed: 1. chest wall resection and right upper lobe lobectomy, 2. right middle lobe sleeve lobectomy, and 3. right lower lobe lobectomy. One instructor was assigned to each operation table, who evaluated each participant's NOTSS scores consisting of 16 elements. RESULTS: When comparing average NOTSS score of all the three procedures, significant differences were observed between Level A, B, and C trainees. As an example of varying elements by procedure, Level A trainees demonstrated differences in Situation Awareness, and a significant difference was observed in Level C trainees regarding the elements of Decision Making. On the contrary, no significant difference was observed among Level B trainees. In the comparison between first-time and experienced participants, a significant improvement was observed in some elements in Level B and C trainees. CONCLUSION: This study highlights the usefulness and feasibility of the NOTSS scoring system for surgeons with different experiences and the effectiveness of providing feedback to trainees during intraoperative handoffs in a wet lab.

Long-term exposure to nitrogen dioxide and natural-cause and cause-specific mortality in Japan.

BACKGROUND: Long-term exposure to air pollution is linked with increased risk of adverse health outcomes, but the evidence for the association between nitrogen dioxide (NO2) and mortality is weak because of the inadequate adjustment of potential confounders and limited spatial resolution of the exposure assessment. Moreover, there are concerns about the independent effects of NO2. Therefore, we examined the association between NO2 long-term exposure and all-cause and cause-specific mortality. METHODS: We included participants who were enrolled in health checkups in Okayama City, Japan, in 2006 or 2007 and were followed until 2016. We used a land-use regression model to estimate the average NO2 concentrations from 2006 to 2007 and allocated them to the participants. We estimated hazard ratios (HRs) for a 10-µg/m3 increase in NO2 levels for all-cause or cause-specific mortality using Cox proportional hazard models. RESULTS: After excluding the participants who were assigned with outlier exposures, a total of 73,970 participants were included in the analyses. NO2 exposure was associated with increased risk of mortality and the HRs and their confidence intervals were 1.06 (95% CI: 1.02, 1.11) for all-cause, 1.02 (0.96, 1.09) for cardiopulmonary, and 1.36 (1.14, 1.63) for lung cancer mortality. However, the elevated risks became equivocal after the adjustment for fine particulate matter except lung cancer. CONCLUSION: Long-term exposure to NO2 was associated with increased risk of all-cause, cardiopulmonary, and lung cancer mortality. The elevated risk for lung cancer was still observable even after adjustment for fine particulate matter.

Clinical Factors Affecting the Dose Conversion Ratio from Intravenous to Oral Tacrolimus Formulation among Pediatric Hematopoietic Stem Cell Transplantation Recipients.

BACKGROUND: Tacrolimus is converted from intravenous to oral formulation for the prophylaxis of graft-versus-host disease when patients can tolerate oral intake and graft-versus-host disease is under control. Oral tacrolimus formulation presents poor bioavailability with intraindividual and interindividual variations; however, some factors affecting its blood concentration among pediatric hematopoietic stem cell transplantation (HCT) recipients are still unclear. This study aimed to identify the clinical factors affecting tacrolimus blood concentrations after switching its formulation. METHODS: Changes in the blood concentration/dose ratio (C/D) of tacrolimus in pediatric HCT recipients were analyzed after the switching of tacrolimus from intravenous to oral formulation. Clinical records of 57 pediatric patients who underwent allogenic HCT from January 2006 to April 2019 in our institute were retrospectively reviewed. The C/D of tacrolimus before discontinuation of intravenous infusion (C/Div) was compared with the tacrolimus trough level within 10 days after the initiation of oral administration (C/Dpo). Multiple linear regression analysis was performed to identify factors affecting (C/Dpo)/(C/Div). RESULTS: The constant coefficient of (C/Dpo)/(C/Div) was 0.1692 [95% confidence interval (CI), 0.137-0.2011]. The concomitant use of voriconazole or itraconazole and female sex were significant variables with a beta coefficient of 0.0974 (95% CI, 0.062-0.133) and -0.0373 (95% CI, -0.072 to -0.002), respectively. CONCLUSIONS: After switching of tacrolimus formulation, pediatric HCT recipients might need oral tacrolimus dose that is 5-6 and 3.5-4.5 times the intravenous dose to maintain tacrolimus blood concentrations and area under the concentration-time curve, respectively. With the concomitant use of voriconazole or itraconazole, an oral tacrolimus dose of 4-5 times the intravenous dose seemed appropriate to maintain blood tacrolimus concentration.

Effects of Household Air Pollution From Solid Fuel Use and Environmental Tobacco Smoke on Child Health Outcomes in Indonesia.

OBJECTIVE: We assessed the combined effect of household air pollution from solid fuel use and from environmental tobacco smoke and child health outcomes in Indonesia. METHODS: Survey subjects self-reported solid fuel use, frequency of indoor smoking, and health outcomes in children. We then evaluated the effect of a combined exposure using multivariate logistic regression. RESULTS: Children exposed to high levels of pollution from solid fuel use had an increased risk of low birth weight, neonatal death, infant death, and acute lower respiratory infection. Exposure to environmental tobacco smoke increased the risk of acute lower respiratory infection. The combined effect of both pollution sources outweighed the independent risk of each exposure alone. CONCLUSIONS: Solid fuel use and environmental tobacco smoke independently increased the risk and child health outcomes and the combined exposure showed the additive effect.