Time elapsed from definitive diagnosis to surgery for osteonecrosis of the femoral head: a nationwide observational study in Japan.

OBJECTIVES: This study documents the time elapsed from the diagnosis of osteonecrosis of the femoral head (ONFH) to surgery, exploring the factors that influence ONFH severity. DESIGN: Retrospective observational study of a nationwide database. SETTING: The Kaplan-Meier method with log-rank tests was applied to examine the period from definitive diagnosis of ONFH to surgery using any surgery as the end point. For bilateral cases, the date of the first surgery was the endpoint. PARTICIPANTS: This study included 2074 ONFH cases registered in 34 university hospitals and highly specialised hospitals of the multicentre sentinel monitoring system of the Japanese Investigation Committee between 1997 and 2018. MAIN OUTCOME MEASURE: The primary outcome was the time from diagnosis to surgery. The secondary outcome was the proportion of subjects remaining without surgery at 3, 6 and 9 months, and at 1, 2 and 5 years after diagnosis. RESULTS: The median time to surgery was 9 months (IQR 4-22 months) after diagnosis of ONFH. The time to surgery was significantly shorter in the alcohol alone group and the combined corticosteroid and alcohol group than in the corticosteroid alone group (p=0.018 and p<0.001, respectively), in early stage ONFH with no or mild joint destruction (stages II and III, p<0.001), and with joint preserving surgery (p<0.001). The proportion without surgery was 75.8% at 3 months, 59.6% at 6 months, 48.2% at 9 months, 40.5% at 1 year, 22.2% at 2 years and 8.3% at 5 years. CONCLUSION: ONFH has been considered to be an intractable disease that often requires surgical treatment, but the fact that surgery was performed in more than half of the patients within 9 months from diagnosis suggests severe disease with a significant clinical impact. TRIAL REGISTRATION NUMBER: Chiba University ID1049.

No association between inactivated influenza vaccination and influenza viral load at diagnosis among young Japanese children: An observational study of the 2013/2014 through 2017/2018 influenza seasons.

BACKGROUND: The association between inactivated influenza vaccination and viral load in young children remains unclear. METHODS: During the 2013/2014 to 2017/2018 influenza seasons in Japan, children under 6 years of age with pre-defined influenza-like illness and influenza-positive status by real-time RT-PCR were recruited at pediatric clinics for this observational study. Influenza viral load was measured for the most predominant subtype/lineage in each season. Using median dichotomized viral load as an outcome, a multilevel logistic regression model was applied to estimate the multivariable adjusted odds ratio (MOR) and 95% confidence interval (CI) for higher viral load. RESULTS: A total of 1,185 influenza-positive children were analyzed. The median log10 viral load copy number (copies per milliliter) was 5.5 (interquartile range, 4.6 to 6.1) and did not differ by vaccination status: 5.5 for unvaccinated, 5.7 for one dose, and 5.5 for two doses (p = 0.67). The MOR of vaccinated (one or two doses) versus unvaccinated children was 1.19 (95% CI: 0.86-1.64). Other factors showing significant associations with higher viral load were positive results for A(H1N1)pdm09 and A(H3N2) in comparison with B/Yamagata. The respective MORs were 3.25 (95% CI: 2.28-4.64) and 1.81 (95% CI: 1.32-2.49). Significantly elevated MORs against higher viral load were also observed for higher body temperature at influenza diagnosis and shorter duration from fever onset to specimen collection. CONCLUSION: No association was observed between inactivated-influenza vaccination and viral load at influenza-positive diagnosis. Influenza subtype/lineage, body temperature, and time elapsed since fever onset were significantly associated with viral load.

Incidence and risk factors for norovirus-related diarrhea in Japanese geriatric intermediate care facilities: A prospective cohort study.

AIM: The risk of developing infectious diarrhea among elderly residents at Japanese geriatric intermediate care facilities is unclear. We investigated the incidence rate and risk factors of norovirus-related diarrhea at such facilities. METHODS: This prospective cohort study followed 1727 residents from November 2018 to April 2020 at 10 geriatric intermediate care facilities in Osaka, Japan regarding the occurrence of diarrhea. Resident data were collected from their medical records using structured forms at two to three of the following three time points: at recruitment, if they developed diarrhea, and when they left the facility. Residents who developed diarrhea were tested using rapid diagnostic tests for norovirus. Cox proportional hazard model was employed to hazard ratios (HRs) with 95% confidence intervals (CIs) to estimate the risk factors for norovirus-related diarrhea. RESULTS: During the study period, 74 residents developed diarrhea, 13 of whom were norovirus positive. The incidence rate of norovirus-related diarrhea was 10.11 per 1000 person-years (95% CI: 4.61-15.61). In terms of risk factors, people with care-needs level 3 were at a higher risk for developing norovirus-related diarrhea (adjusted HR [aHR] = 7.35, 95% CI: 1.45-37.30). Residents with hypertension (aHR = 3.41, 95% CI: 1.05-11.04) or stroke (aHR = 8.84, 95% CI: 2.46-31.83), and those who walked with canes (aHR = 16.68, 95% CI: 1.35-206.52) also had a significantly higher risk for norovirus-related diarrhea. CONCLUSIONS: Throughout the study period, the incidence of development of diarrhea was low. Care-needs level 3, stroke, hypertension and use of a cane were identified as risk factors for norovirus-related diarrhea in Japanese geriatric intermediate care facilities. Geriatr Gerontol Int 2023; 23: 179-187.

Palladium(0)-Catalyzed Anti-Selective Addition-Cyclizations of Alkynyl Electrophiles.

Invited for the cover of this issue is the group of Hirokazu Tsukamoto at Tohoku University (current affiliation: Yokohama University of Pharmacy). The image depicts anti-selective arylative cyclization reactions of alkynyl aldehydes with arylboronic acids under palladium catalysis in methanol to afford endo- and exo-cyclic products. Read the full text of the article at 10.1002/chem.202203068.

Palladium(0)-Catalyzed Anti-Selective Addition-Cyclizations of Alkynyl Electrophiles.

Palladium(0)/monophosphine complexes catalyze anti-selective alkylative, arylative, and alkynylative cyclizations of alkynyl electrophiles with organometallic reagents. The remarkable anti-selectivity results from novel oxidative addition, that is, the nucleophilic attack of electron-rich palladium(0) on the electrophile across the alkyne followed by transmetalation and reductive elimination ("anti-Wacker"-type cyclization). With regard to 5-alkynals, triphenylphosphine (PPh3 )-ligated palladium(0) catalyzes the cyclization of terminal alkynes and conjugated alkenyl- or alkynyl-substituted ones to afford 2-cyclohexen-1-ol and 2-alkylidene-cyclopentanol derivatives, respectively. For 6-alkyl- or 6-aryl-5-alkynals, the cyclization does not proceed with the palladium/PPh3 catalyst; however, it does proceed with palladium/tricyclohexylphosphine (PCy3 ), to yield the former products predominantly. Remarkably, the latter catalyst completely switches the regioselectivity in the cyclization of the conjugated diyne-aldehydes. Notably, palladium/PPh3 -catalyzed cyclizations also proceed with other organometallics or even without them.

Geographic distribution of the incidence of osteonecrosis of the femoral head in Japan and its relation to smoking prevalence.

OBJECTIVES: Alcohol intake and smoking are modifiable lifestyle-related risk factors for osteonecrosis of the femoral head (ONFH). We investigated geographic differences in ONFH incidence in Japan and the correlation with alcohol intake and smoking to develop prevention strategies for ONFH in Japan. METHODS: This ecological study was conducted in Japan primarily using the following data sources: nationwide epidemiological survey and national survey. We estimated the annual ONFH incidence and the prevalence of alcohol drinking and smoking in each prefecture. Prefectural incidence and prevalence were calculated by sex and age-standardization. RESULTS: The mean annual ONFH incidence per 100,000 population was 3.08 in men and 1.63 in women, respectively. There was no significant correlation between ONFH incidence and the prevalence of any levels of alcohol intake, while smoking ≥20 cigarettes/day showed a significant and moderate correlation in men (r = 0.47, p = .01). This correlation remained significant after adjustment for the prevalence of any levels of alcohol intake (standardized partial regression coefficient = 0.47-0.49, p = .009-.01). CONCLUSION: ONFH incidence is geographically variable in Japan, and this may be partly explained by the distribution of smoking prevalence. Smoking cessation may contribute to an effective decline in the overall ONFH incidence in Japan.

Epidemiological study of osteonecrosis of the femoral head using the national registry of designated intractable diseases in Japan.

OBJECTIVES: We aimed to investigate the epidemiological characteristics of osteonecrosis of the femoral head (ONFH) using the designated intractable diseases (DID) database in Japan. METHODS: Data on patients who had received public subsidies for medical costs due to ONFH from 2012 to 2013 were extracted from the DID database. The incidence and prevalence of ONFH, distribution of gender, age, and the prevalence of associated risk factors were assessed. These epidemiological characteristics were compared with those of another nationwide ONFH survey conducted during a similar period. RESULTS: Data on 3264 newly diagnosed patients (incident cases) and 20,042 patients registered until 2013 (prevalent cases) were evaluated. The corrected annual incidence and prevalence of ONFH per 100,000 were 3.0 and 18.2-19.2, respectively. The ratio of males to females was 1.4 in 2012 and 1.2 in 2013, respectively. Peak distribution was observed at ages 40s and 60s in males and females, respectively. The prevalence of the risk factors were steroid-associated: 39%, alcohol-associated: 30%, both: 4%, and none: 27%. CONCLUSIONS: The DID database data showed a similar distribution of gender and age to that in other nationwide surveys but lower incidence and prevalence of ONFH. Sampling bias may affect the epidemiological characteristics of ONFH.

Influence of Prior Influenza Vaccination on Current Influenza Vaccine Effectiveness in Children Aged 1 to 5 Years.

BACKGROUND: Although annual influenza vaccination is an important strategy used to prevent influenza-related morbidity and mortality, some studies have reported the negative influence of prior vaccination on vaccine effectiveness (VE) for current seasons. Currently, the influence of prior vaccination is not conclusive, especially in children. METHODS: We evaluated the association between current-season VE and prior season vaccination using a test-negative design in children aged 1-5 years presenting at nine outpatient clinics in Japan during the 2016/17 and 2017/18 influenza seasons. Children with influenza-like illness were enrolled prospectively and tested for influenza using real-time RT-PCR. Their recent vaccination history was categorized into six groups according to current vaccination doses (0/1/2) and prior vaccination status (unvaccinated = 0 doses/vaccinated = 1 dose or 2 doses): (1) 0 doses in the current season and unvaccinated in prior seasons (reference group); (2) 0 doses in the current season and vaccinated in a prior season; (3) 1 dose in the current season and unvaccinated in a prior season; (4) 1 dose in the current season and vaccinated in a prior season; (5) 2 doses in the current season and unvaccinated in a prior season, and (6) 2 doses in the current season and vaccinated in a prior season. RESULTS: A total of 799 cases and 1196 controls were analyzed. The median age of the subjects was 3 years, and the proportion of males was 54%. Overall, the vaccination rates (any vaccination in the current season) in the cases and controls were 36% and 53%, respectively. The VEs of the groups were: (2) 29% (95% confidence interval: -25% to 59%); (3) 53% (6% to 76%); (4) 70% (45% to 83%); (5) 56% (32% to 72%), and (6) 61% (42% to 73%). The one- and two-dose VEs of the current season were significant regardless of prior vaccination status. The results did not differ when stratified by influenza subtype/lineage. CONCLUSION: Prior vaccination did not attenuate the current-season VE in children aged 1 to 5 years, supporting the annual vaccination strategy.

Cerebrospinal Fluid Protein Concentration in Healthy Older Japanese Volunteers.

The concentration of cerebrospinal fluid total protein (CSF-TP) is important for the diagnosis of neurological emergencies. Recently, some Western studies have shown that the current upper reference limit of CSF-TP is quite low for older patients. However, little is reported about the concentration of CSF-TP in the older Asian population. In this study, we retrospectively analyzed the CSF-TP concentrations in healthy older Japanese volunteers. CSF samples in 69 healthy Japanese volunteers (age range: 55-73 years) were collected by lumbar puncture, and the data of CSF were retrospectively analyzed. The mean (standard deviation) CSF-TP was 41.7 (12.3) mg/dL. The older group (≥65 years old) had higher CSF-TP concentration than the younger group (55-64 years old). The 2.5th percentile and 97.5th percentile of CSF-TP were estimated as 22.5 and 73.2 mg/dL, respectively, which were higher than the current reference range in Japan (10-40 mg/dL). Conclusions: The reference interval of CSF-TP in the older population should be reconsidered for the precise diagnosis of neurological emergencies.

Factors associated with high care burden of primary caregivers of children with medical complexity after completing a discharge-support program in a recovery center.

INTRODUCTION: Recently, many seriously ill children requiring medical equipment are being recommended to transition from hospital to home care in Japan. Since 2011, our recovery center has provided a support program for the transfer process from hospital to home for ill children and their families. The purpose of this study was to evaluate the factors related to high care burden after completing the discharge-support program. METHODS: A questionnaire-based cross-sectional study was conducted on all primary caregivers whose children received the program in our center and moved from hospital to home (30 children and 29 families) from May 2011 to May 2018. Fifteen children came from the neonatal intensive care unit. The questionnaire consisted of three parts: characteristics of children and families and life after the program; the Zarit Burden Interview (ZBI); and the Positive and Negative Affect Schedule (PANAS). RESULTS: Twenty-three primary caregivers responded (79% response rate). All children received tracheostomy and 71% received home mechanical ventilation. Primary caregivers were all mothers. High ZBI score was not related to the severity and type of medical equipment. There were relationships between high ZBI score and following factors: 'unimproved relationship between patients and family members without primary caregivers' and 'additional medical equipment after discharge'. The result of PANAS showed that positive attitude was not different between those with high and low ZBI scores. CONCLUSION: It is crucial to reach out to family members without a primary caregiver. Additional medical care/equipment after the program is related to the care burden of primary caregivers.

Statistical Analysis of the Axillary Temperatures Measured by a Predictive Electronic Thermometer in Healthy Japanese Adults.

Body temperature is important for diagnosing illnesses. However, its assessment is often a difficult task, considering the large individual differences. Although 37 °C has been the gold standard of body temperature for over a century, the temperature of modern people is reportedly decreasing year by year. However, a mean axillary temperature of 36.89 ± 0.34 °C reported in 1957 is still cited in Japan. To assess the measured axillary temperature appropriately, understanding its distribution in modern people is important. This study retrospectively analyzed 2454 axillary temperature measurement data of healthy Japanese adults in 2019 (age range, 20-79 years; 2258 males). Their mean temperature was 36.47 ± 0.28 °C (36.48 ± 0.27 °C in males and 36.35 ± 0.31 °C in females). Approximately 5% of the 20-39-year-old males had body temperature ≥37 °C, whereas 8% had a temperature ≥ 37 °C in the afternoon. However, none of the subjects aged ≥50 years reported body temperature ≥37 °C. In multivariable regression analysis, age, blood pressure, pulse rate, and measurement time of the day were associated with axillary temperature. Our data showed that the body temperature of modern Japanese adults was lower than that reported previously. When assessing body temperature, the age, blood pressure, pulse rate, and measurement time of the day should be considered.

SARS-CoV-2 Seroprevalence among Healthcare Workers in General Hospitals and Clinics in Japan.

Coronavirus disease 2019 (COVID-19) has become a serious public health problem worldwide. In general, healthcare workers are considered to be at higher risk of COVID-19 infection. However, the prevalence of COVID-19 among healthcare workers in Japan is not well characterized. In this study, we aimed to examine the seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies among 2160 healthcare workers in hospitals and clinics that are not designated to treat COVID-19 patients in Japan. The prevalence of SARS-CoV-2 immunoglobulin G was 1.2% in August and October 2020 (during and after the second wave of the pandemic in Japan), which is relatively higher than that in the general population in Japan (0.03-0.91%). Because of the higher risk of COVID-19 infection, healthcare workers should be the top priority for further social support and vaccination against SARS-CoV-2.

Variability of post-void residual urine volume and bladder voiding efficiency in patients with underactive bladder.

OBJECTIVES: Post-void residual urine volume (PVR) and bladder voiding efficiency (BVE) are widely used as clinical parameters to evaluate patients with voiding dysfunction. The present study was conducted to assess the variability of PVR and BVE determinations in patients with underactive bladder (UAB). In addition, we focused on the bladder volume prior to voiding (BVvoid ) that may influence PVR and BVE, and investigated a correlation between PVR and BVvoid , and between BVE and BVvoid . METHODS: Ten patients with a symptom complex of UAB, who had PVR of 50 mL or greater, were admitted to hospital during a 24-hour period for the measurement of voided volume (VV) and PVR. PVR was measured by transabdominal ultrasonography. BVE was expressed by a fraction (%) of bladder volume evacuated ([VV/BVvoid ] × 100). RESULTS: Ten patients, five men (mean age of 65.0 years) and five women (mean age of 70.2 years), participated in this study. Regardless of gender, there was a large variation in repeated measurements of PVR in an individual patient. PVR increased with an increase in BVvoid , and there was a significant linear relationship between PVR and BVvoid . BVE was approximately constant after every voiding in each patient, and there was no significant linear relationship between BVE and BVvoid . CONCLUSIONS: Measurement of PVR was unreliable because of wide variation in the same individual. The variation of BVE was much smaller than PVR. BVE would be a reliable parameter with good reproducibility for the assessment of emptying function.

Lifestyles Associated with Prognosis After Eradication of Hepatitis C Virus: A Prospective Cohort Study in Japan.

BACKGROUND: Hepatocellular carcinoma develops in some patients with hepatitis C virus (HCV), even after achieving sustained virological response (SVR). AIMS: We examined factors associated with liver disease progression in a prospective cohort study of SVR patients. METHODS: Participants were patients who had visited a hospital for clinical follow-up of chronic HCV infection in 2005 and had reached SVR as a result of subsequent antiviral treatment. Baseline information including lifestyle and dietary habits before SVR was collected in 2005 using self-administered questionnaires, and clinical information before SVR was collected from medical records in 2005. Study outcome was liver disease progression such as liver cirrhosis, hepatocellular carcinoma, and/or liver disease-related death after SVR. Proportional hazard models were employed to calculate hazard ratios (HRs) and 95% confidence intervals for each variable. RESULTS: Of 180 SVR patients, 27 patients (15%) showed liver disease progression after SVR: 26 (14%) were diagnosed with liver cirrhosis, two (1%) with hepatocellular carcinoma, and/or one (0.6%) with liver-disease-related death. Besides older age at SVR (HR = 11.9, P < 0.01) and aspartate aminotransferase-to-platelet ratio index score ≥ 1.0 before SVR (HR = 2.63, P = 0.03), alcohol drinkers before SVR (HR = 2.82, P = 0.06) were suggested to be associated with liver disease progression after SVR, whereas higher consumption of vitamin B12 before SVR showed a decreased HR for liver disease progression (HR = 0.41, P = 0.09). CONCLUSIONS: Alcohol drinking might be associated with liver disease progression, whereas vitamin B12 intake might have protective effects against liver disease progression after eradication of HCV. Further studies are needed to confirm these findings.

Comparison of immunogenicity between candidate influenza A(H3N2) virus vaccine strains in Japan: A randomized controlled trial using a monovalent vaccine of A/Saitama/103/2014 (CEXP-002) and A/Hong Kong/4801/2014 (X-263).

BACKGROUND: For the 2017-18 influenza season, A/Saitama/103/2014 (CEXP-002) (Saitama strain) was antigenically more similar to prior circulating strains than A/Hong Kong/4801/2014 (X-263) (Hong Kong strain) in a ferret model and was selected as the A(H3N2) vaccine virus strain in Japan. However, the Saitama strain grew poorly, and the Japanese government switched to the Hong Kong strain, raising public concerns of poor effectiveness. To enhance understanding of the correlation between antigenicity in experimental models and immunogenicity, as a surrogate measure of vaccine effectiveness, in the human population, we compared the immunogenicity of specially-prepared single dose monovalent influenza A(H3N2) vaccines containing the Saitama or the Hong Kong strain. METHODS: A randomized controlled trial of 100 healthy adults aged 20-64 years (n = 50/group) was conducted. Virus neutralization assay was performed on sera from days 0 (pre-vaccination) and 21 (post-vaccination). Geometric mean titer (GMT), mean fold rise (MFR), seroconversion proportion (SCP), and seroprotection proportion (SPP) were calculated for vaccine strains and a representative circulating A(H3N2) virus strain (A/Osaka/188/2017). RESULTS: For the Hong Kong strain, post-vaccination GMT was significantly higher in the Hong Kong vaccine recipients (1:546 vs 1:260, p < 0.01), but MFR, SCP, and SPP were similar for both vaccine groups. For the Saitama strain, post-vaccination GMT (1:116 vs 1:61, p = 0.01) and SPP (86% vs 68%, p = 0.03) were significantly higher in the Hong Kong vaccine recipients, but MFR and SCP were similar for both vaccine groups. Against A/Osaka/188/2017, post-vaccination GMT and MFR were similar in both vaccine groups, but SCP (32% vs 4%, p < 0.01) and SPP (28% vs. 6%, p < 0.01) were significantly higher in the Hong Kong vaccine recipients. CONCLUSION: The Hong Kong vaccine induced better or equivalent immunogenicity in comparison to the Saitama vaccine. Our trial showed that antigenic similarity in experimental models does not necessarily correlate with immunogenicity in the human population. CLINICAL TRIAL REGISTRATION: UMIN000029293.

The association between sacral morphology and sacroiliac joint conformity demonstrated on CT-based bone models.

INTRODUCTION: Knowledge of the stress distribution on structures around the sacroiliac joint (SIJ) is required to treat or prevent SIJ disorders. The purpose of this study was to reveal the association between sacral morphology and SIJ conformity. MATERIALS AND METHODS: This cross-sectional study included 11 adult patients with unilateral SIJ pain who underwent computed tomography (CT) imaging of the pelvis. Bony coordinate systems for the sacrum and innominates were embedded using anatomical landmarks. Local coordinate systems for the auricular surfaces of the sacrum and innominate were also defined. Conformity of the SIJ was quantified by the offset of the coordinate systems between the auricular surfaces of the sacrum and innominate. Repeated measure ANOVA and multiple regression analysis were used for statistical analyses. RESULTS: There were large variations across subjects in sacral morphology and SIJ conformity. There were no differences in any of the six degrees-of-freedom positions or orientations of the bilateral sacral and innominate auricular surfaces between the symptomatic and asymptomatic sides. The SIJ downward rotation on the asymptomatic and symptomatic sides were 0.0 [-1.0, 1.1]° and 2.1 [1.2, 3.0]°, respectively. Smaller downward rotation of the sacral auricular surface based on the sacral bony coordinate system had significant association with the greater SIJ downward rotation (standard partial regression coefficient: -.44, p = .043). CONCLUSIONS: The results indicate that the morphology of the sacrum is associated with poor SIJ conformity and that separation of the superior portion of the SIJ can be a risk factor for SIJ pain.

Lactobacillus reuteri DSM 17938 and Magnesium Oxide in Children with Functional Chronic Constipation: A Double-Blind and Randomized Clinical Trial.

OBJECTIVE: Chronic functional constipation is a frequent condition. The aim of the study was to evaluate the efficacy of the probiotic Lactobacillus (L.) reuteri DSM 17938 and magnesium oxide (MgO) for relieving chronic functional constipation in children. STUDY DESIGN: A prospective, double-blind, placebo-controlled, randomized, and parallel-group trial was conducted in five pediatric outpatient clinics in Japan. Sixty patients who were more than six months old and under six years of age with a diagnosis of functional constipation according to Rome IV criteria were randomly divided into three groups: group A (n = 20) received L. reuteri DSM 17938 and lactose hydrate as a placebo of MgO; group B (n = 19) received L. reuteri DSM 17938 and MgO; and group C (n = 21) received a placebo of L. reuteri DSM 17938 and MgO. RESULTS: All three groups exhibited significant improvement in defecation frequency in the fourth week compared with the baseline condition (group A: p < 0.05; group B: p < 0.05; group C: p < 0.05). The MgO group and combination group showed a significant decrease in stool consistency, but the L. reuteri DSM 17938 group did not (group A: p = 0.079; group B: p < 0.05; group C: p < 0.05). MgO significantly suppressed the presence of the genus Dialister. Defecation frequency negatively correlated with the frequency of Clostridiales-belonging bacteria among the gut microbiome. CONCLUSIONS: L. rueteri DSM 17938 and MgO were both effective in the management of functional constipation in young children. MgO caused an imbalance in the gastrointestinal microbiome, which was not the case in the probiotic group.

Safety of influenza vaccination on adverse birth outcomes among pregnant women: A prospective cohort study in Japan.

BACKGROUND: Pregnant women are in the highest priority group for receiving influenza vaccination. However, they may be reluctant to receive the vaccination due to concerns about the influence of vaccination on the fetuses. METHODS: This prospective cohort study of 10 330 pregnant women examined the safety of influenza vaccination in terms of adverse birth outcomes. Influenza vaccination during pregnancy was determined from questionnaires before and after the 2013/2014 influenza season. All subjects were followed until the end of their pregnancy. Adverse birth outcomes, including miscarriage, stillbirth, preterm birth, low birth weight, and malformation, were assessed by obstetrician reports. RESULTS: Adverse birth outcomes were reported for 641 (10%) of the 6387 unvaccinated pregnant women and 356 (9%) of the 3943 vaccinated pregnant women. Even after adjusting for potential confounders, vaccination during pregnancy showed no association with the risk of adverse birth outcomes (odds ratio 0.90, 95% confidence interval 0.76-1.07). Vaccination during the first or second trimester displayed no association with adverse birth outcomes, whereas vaccination during the third trimester was associated with a decreased risk of adverse birth outcomes (odds ratio 0.70, 95% confidence interval 0.51-0.98). CONCLUSIONS: Influenza vaccination during pregnancy did not increase the risk of adverse birth outcomes, regardless of the trimester in which vaccination was performed, when compared to unvaccinated pregnant women.

Palladium(0)-Lithium Iodide Cocatalyzed Asymmetric Hydroalkylation of Conjugated Enynes with Pronucleophiles Leading to 1,3-Disubstituted Allenes.

Axially chiral 1,3-disubstituted allenes were synthesized via hydroalkylation of alkyl- or aryl-substituted conjugated enynes (readily prepared via a Sonogashira reaction) with pronucleophiles such as dimethyl malonate under the cocatalysis of DTBM-SEGPHOS-ligated palladium and lithium iodide. Although the palladium catalyst ligated with (S)-DTBM-SEGPHOS prefers the formation of (R)-1,3-disubstituted allenes, lithium iodide recovers and increases the intrinsic selectivity producing (S)-allenes by promoting the isomerization of the exo-alkylidene-π-allylpalladium intermediate prior to the nucleophilic substitution step.

The association between environmental factors and the development of Crohn's disease with focusing on passive smoking: A multicenter case-control study in Japan.

BACKGROUND: The number of patients with Crohn's disease (CD) in Japan has recently been increasing. We examined the association between environmental factors and the development of CD in Japanese focusing on passive smoking. METHODS: We conducted a multicenter case-control study and compared the environmental factors of 93 cases who were newly diagnosed with CD to the environmental factors of 132 controls (hospital-, age-, and sex-matched patients with other diseases). The odds ratio (OR) of each factor for the development of CD and the 95% confidence interval (CI) were calculated using a logistic regression model. The association between the details of passive smoking history and the development of CD was examined for those who had an active smoking history "no". Odds ratios of number of passively smoked cigarettes (per day), time of passive smoking (per day) and period of passive smoking (year) were calculated using "passive smoking 'No'" as a reference. RESULTS: History of appendicitis, family history of inflammatory bowel disease, and active smoking history were not significantly associated with the development of CD. Drinking history showed a decreased OR for the development of CD (0.39, 0.19-0.77). "Passive smoking Yes" showed significantly increased OR (2.49, 1.09-5.73). Regarding the association between passive smoking and the development of CD, the OR increased as the number of cigarettes per day, smoking time per day, and smoking duration increased, and there was a dose-response relationship (trend P = 0.024, 0.032, 0.038). CONCLUSIONS: The association between environmental factors and the development of CD among Japanese was examined by case-control study. It was suggested that the passive smoking history may be associated to the development of CD.