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External ventricular drainage (EVD) is required to resolve acute hydrocephalus associated with intraventricular hemorrhage (IVH). The correlation of scoring systems of IVH with indications for EVD for acute hydrocephalus related to IVH is currently unknown.We identified 213 hypertensive patients with IVH and divided them into 2 groups according to treatment method: 187 patients receiving blood pressure control alone and 26 patients undergoing EVD. The following patients were excluded: pediatric patients, patients undergoing intracranial hematoma removal, patients with fetal status, and patients without sufficient clinical data. We compared the Glasgow Coma Scale score, Graeb score, LeRoux score, Evans index, and bicaudate index values between the 2 groups and determined the prognostication accuracy of each scoring system.There were significant differences in all 4 scoring systems between the 2 groups (P 0.001). The cutoff values (sensitivity and specificity) of each scoring system were as follows: Glasgow Coma Scale, 8 (65.4%, 87.7%); Graeb score, 6 (80.8%, 75.4%); LeRoux score, 9 (80.8%, 76.5%); Evans index, 0.245 (80.8%, 67.9%); and bicaudate index, 0.186 (76.9%, 76.5%). The value of the area under the curve of each scoring system (95% confidence interval) was as follows: Glasgow Coma Scale, 0.806 (0.705-0.907); Graeb score, 0.852 (0.779-0.925); LeRoux score, 0.875 (0.812-0.937); Evans index, 0.788 (0.702-0.875); and bicaudate index, 0.778 (0.673-0.883).The LeRoux score is better for identifying patients with IVH who are more likely to have EVD.

Background: The appropriateness of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) lesions has rarely been investigated. Methods and Results: The Japanese CTO-PCI Expert Registry enrolled consecutive patients undergoing CTO-PCI carried out by highly experienced Japanese CTO specialists who performed more than 50 CTO-PCIs per year and 300 CTO-PCIs in total. This study included patients undergoing CTO-PCI between January 2014 and December 2019. The appropriateness, trends, and differences among the procedures performed by the operators using the 2017 appropriate use criteria were analyzed. Furthermore, we performed a logistic regression analysis to assess whether the appropriateness was associated with in-hospital major adverse cardiovascular and cerebrovascular events (MACCE). Of the 5, 062 patients who underwent CTO-PCI, 4, 309 (85.1%) patients who did not undergo the non-invasive stress test were classified as having no myocardial ischemia. Of the total cases, 3, 150 (62.2%) were rated as “may be appropriate, ” and 642 (12.7%) as “rarely appropriate” CTO-PCI cases. The sensitivity analyses showed that the number (%) of “may be appropriate” ranged from 4, 125 (57.8%) to 4, 744 (66.4%) and the number of “rarely appropriate” ranged from 843 (11.8%) to 970 (13.6%) among best and worst scenarios. Conclusions: In a large Japanese CTO-PCI registry, approximately 13% of CTO-PCI procedures were classified as “rarely appropriate”. Substantial efforts would be required to decrease the number of “rarely appropriate” CTO-PCI procedures.

BACKGROUND/PURPOSE The purpose of the present study was to investigate the possibility of reducing clinical impacts of acute necrotic collection (ANC) on patients with acute pancreatitis (AP) using recombinant human soluble thrombomodulin (rTM). METHODS In this retrospective multicenter study, 233 consecutive AP patients with ANC and acute peripancreatic fluid collection (APFC) from 2012 to 2016 were enrolled. To assess clinical impacts of ANC, severity on admission (JPN score, JPN CT grade, and Modified CT severity index), development of walled-off necrosis (WON), imaging costs for follow-up, and mortality were recorded. Finally, we investigated whether rTM could reduce the clinical impacts, adjusting the severity using propensity analysis with Inverse probability of treatment weighting. RESULTS Patients with ANC developed WON with higher ratio than APFC (58/98 [59.2%] vs 20/135 [14.8%], OR = 8.3, P

Long-term acetaminophen (APAP) use has poorly defined effects on renal function. We investigated these effects using a real-world database. We used a database of health data routinely collected from 185 hospitals serving 20 million patients in Japan. Individuals with chronic pain were selected for the study. The primary outcome was the change in renal function, as measured by 1/serum creatinine (SCr) during the postindex period. After excluding individuals who did not meet the inclusion criteria, 241,167 patients were included in the analysis (median age 79.0, range 65–101 years; 111,252 were men). APAP was prescribed significantly more frequently to patients with a low renal function (P

Background: We have sometimes observed interstitial pneumonia which had chronic course and unknown causes but not diagnosed as idiopathic pulmonary fibrosis (IPF). However, the treatment strategy was not established definitely. To clarify the usefulness of cyclosporin A (CsA) in idiopathic chronic fibrosing interstitial pneumonia (iCFIP) without IPF, we examined longitudinal changes in pulmonary physiology. Methods: Japanese patients with iCFIP without IPF treated with CsA were identified retrospectively. Linear mixed-effects models were used to evaluate changes in pulmonary physiology after adjusting for age, sex, and smoking history. Primary outcomes were longitudinal trajectories of the percent predicted forced vital capacity (%FVC), percent predicted diffusing capacity for carbon monoxide (%DLco), and composite physiologic index (CPI) before and after CsA. Results: Thirty-three patients were included. Before CsA initiation, %FVC, %DLco, and CPI declined at rates of 9.1%, 8.6% and −7.1 per 1 year, respectively. After CsA initiation, the gradient of %FVC showed significant improvements in 0–1 years (6.2%±3.0%; P

Mounting evidence suggests that preoperative nutritional status can predict postoperative outcomes in patients with non-small cell lung cancer. However, a consensus on the optimal evaluation tool among the various nutritional assessment methods has not been reached. This study aimed at validating the predictive value of 3 nutritional scoring systems for clinical outcomes in patients with completely resected non-small cell lung cancer.We retrospectively reviewed the preoperative data of 475 consecutive patients with completely resected non-small cell lung cancer to assess the following 3 albumin-based nutritional methods: prognostic nutritional index, controlling nutritional status score, and geriatric nutritional risk index.Receiver operating characteristic curves of the prognostic nutritional index, controlling nutritional status score, and geriatric nutritional risk index identified the optimal cutoff values for predicting the postoperative complications as 47, 2, and 101, respectively. Stratification of patients using these cutoff values indicated a higher postoperative complication rate in the malnutrition group than in the group with proper nutrition (P .05 for all nutritional assessment methods). Additionally, patients with malnutrition exhibited significantly lower 5-year overall and recurrence-free survivals, regardless of the assessment method (P .05 for all 3 nutritional assessment methods). Multivariate analyses showed that all 3 nutritional parameters were independent prognostic factors for overall survival after lung resection.The 3 nutritional assessment methods we used were found to have high predictive values for postoperative complications and survival. Preoperative nutritional conditioning may improve the postoperative outcomes in patients with resectable non-small cell lung cancer.

Background and objective Interstitial lung disease (ILD) is a common pulmonary manifestation of systemic sclerosis (SSc). It is unknown whether radiographic fibrosis score predicts mortality in SSc-associated ILD (SSc-ILD). We retrospectively analysed patients with SSc-ILD to evaluate whether radiographic fibrosis score was a useful predictor of mortality. Methods We identified SSc-ILD patients evaluated at Kurashiki Central Hospital (Japan) from 2006 to 2016, and radiographic fibrosis scores based on the extent of reticulation and honeycombing on high-resolution computed tomography (HRCT) scanning were calculated by manually tracing around each fibrotic area. Independent predictors of overall survival were determined using the Cox proportional hazards model. Results The study included 48 patients, of whom 19 had usual interstitial pneumonia on HRCT. The median follow-up period was 56.6 months, and over the follow-up period 15 patients died. The 5-year survival was 72.4%. In the multivariate analysis, radiographic fibrosis score, age, being male and forced vital capacity were independently associated with an increased risk of death, while HRCT pattern was not. Conclusion A high radiographic fibrosis score was a poor prognostic factor in SSc-ILD. More widespread fibrosis was associated with an increased risk of death, independent of HRCT pattern.

This study aimed to investigate the usefulness of procalcitonin-guided therapy in hospitalized community-acquired pneumonia patients to reduce antibiotic duration and costs without worsening prognosis.352 hospitalized community-acquired pneumonia patients in an observational cohort study in which procalcitonin was measured three times serially, on admission (Day 1) and 2-3 days (Day 3) and 6-8 days (Day 7) after admission, between October 2010 and February 2016 were reviewed retrospectively. Antibiotics could be stopped if Day 7 procalcitonin was0.25 ng mLUsing theoretical procalcitonin guidance, antibiotic duration could be reduced from 12.6 to 8.6 days (P 0.001), while costs could be reduced from 45,833 to 38,952 yen (P = 0.005). Among the patients in whom theoretical procalcitonin guidance could be adopted, recurrence rates (5.6% vs. 8.1%, P = 0.15) and mortality rates (0% vs. 5.1%, P = 0.07) did not worsen between the group having the same antibiotic durations as with theoretical procalcitonin guidance in actual practice (N = 71) and the group having durations more than 2 days longer in actual practice than in theoretical procalcitonin guidance (N = 198). There was no significant difference in pneumonia severity using A-DROP, CURB-65, and PSI between two groups.Procalcitonin-guided therapy may be useful in hospitalized community-acquired pneumonia patients to reduce antibiotic duration and costs without worsening the prognosis.

Supplemental Digital Content is available in the text, Recent large observational studies of antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) show that severe infection is a major cause of death and that the majority of infections occur during the early phase of initiating remission-induction therapy. Many risk factors for severe infection have been suggested, but these have been inconsistent. Nevertheless, infectious risk factors in elderly patients with AAV have not been adequately investigated in previous studies. In this retrospective observational study, we examined potential predictors of severe infection within 90 days (early severe infections) after remission-induction therapy in patients with AAV aged 65 years or older. We included 167 consecutive elderly patients with AAV admitted to our hospital. Data from medical history and remission-induction therapy were analyzed for predictive risk factors associated with early severe infections. The relationship between initial doses of corticosteroids and cumulative incidence of severe infections was also analyzed. A multivariate analysis of risk factors for early severe infections was performed using logistic regression analysis. The Kaplan–Meier method was used to estimate the overall survival, and the log-rank test was used to evaluate the differences between patients with and without early severe infections. Gray method was used to compare the cumulative incidence of severe infections in patients who did and did not receive initial high-dose corticosteroids. Logistic regression analysis showed that initial high-dose corticosteroid administration (prednisolone ≥0.8 mg/kg/d) (odds ratio [OR] 3.86, P = .030) and serum creatinine levels at diagnosis ≥1.5 mg/dL (OR 5.13, P = .003) were independent predictors of early severe infection although administration of cyclophosphamide or rituximab was not. The cumulative incidence of severe infections was also significantly higher in patients who received initial high-dose corticosteroids (P = .042), and patients with early severe infections exhibited a high mortality rate within 6 months (P

Whether macrolide combination therapy reduces the mortality of patients with severe community-acquired pneumonia (CAP) hospitalized in the non-intensive care unit (ICU) remains unclear. Therefore, we investigated the efficacy of adding azithromycin to β-lactam antibiotics for such patients. This prospective cohort study enrolled consecutive patients with CAP hospitalized in the non-ICU between October 2010 and November 2016. The 30-day mortality between β-lactam and azithromycin combination therapy and β-lactam monotherapy was compared in patients classified as mild to moderate and severe according to the CURB-65, Pneumonia Severity Index (PSI), and Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) criteria. Inverse probability of treatment weighting (IPTW) analysis was used to reduce biases. Based on the CURB-65 and PSI, combination therapy did not significantly reduce the 30-day mortality in either group (179 patients in the combination group, 952 in the monotherapy group). However, based on the IDSA/ATS criteria, combination therapy significantly reduced the 30-day mortality in patients with severe (odds ratio [OR] 0.12, 95% confidence interval [CI] 0.007–0.57), but not non-severe pneumonia (OR 1.85, 95% CI 0.51–5.40); these results were similar after IPTW analysis. Azithromycin combination therapy significantly reduced the mortality of patients with severe CAP who met the IDSA/ATS criteria.

The usefulness of existing pneumonia severity indices for predicting mortality in nursing and healthcare-associated pneumonia (NHCAP) is unclear. This study compared the usefulness of existing pneumonia severity indices for predicting mortality in NHCAP and community-acquired pneumonia (CAP). Consecutive hospitalized pneumonia patients including NHCAP and CAP patients were prospectively enrolled between October 2010 and November 2017. Admission pneumonia severity was assessed using CURB-65, Pneumonia Severity Index (PSI), A-DROP, Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) severe pneumonia criteria, and I-ROAD. The primary outcome was 30-day mortality. The discriminatory ability of each severity index was evaluated by receiver operating characteristic curve analysis. Overall, 828 patients had NHCAP, and 1330 patients had CAP. Thirty-day mortality was 12.8% and 5.6% in NHCAP and CAP patients, respectively. The area under the curve of PSI (0.717, 95% confidence interval 0.673–0.761) was the highest among all pneumonia severity indices, with significant differences compared with CURB-65 (0.651, 95% confidence interval 0.598–0.705, P = 0.02) and IDSA/ATS severe pneumonia criteria (0.659, 95% confidence interval 0.612–0.707, P = 0.03). The predictive abilities for 30-day mortality of the pneumonia severity indices, excluding PSI and I-ROAD, were significantly inferior for NHCAP than for CAP. PSI may be the most useful pneumonia severity score for predicting mortality in NHCAP. However, the predictive ability for mortality of each pneumonia severity score was worse for NHCAP than for CAP; therefore, the prognostic factors in NHCAP need to be identified for better management of NHCAP patients.

Aim Deteriorated health-related quality of life (HRQOL) is associated with increased risk for death in both chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients; however, the impact of HRQOL on CKD progression is not well investigated. Methods We aimed to evaluate the association between HRQOL and CKD progression in Japanese patients with CKD. One hundred and three outpatients who visited the department of nephrology at our hospital (mean estimated glomerular filtration rate (eGFR); 32.1 ± 11.2 mL/min per 1.73 m2 ) between April 2007 and March 2012 were enrolled in this study. The primary outcome was 30% decline of eGFR or ESRD. We assessed HRQOL of all participants at baseline, including the physical component summary (PCS), the mental component summary (MCS) and the role/social component summary (RCS), using SF-36. Based on the baseline score of PCS, MCS and RCS, we divided all subjects into two groups by median. Results We studied 66 men (64.1%) and 37 women aged 61.7 ± 10.0 years old. During approximately 2.5 years of follow-up period, 59 patients (57.3%) reached 30% eGFR decline or ESRD. Cox regression analyses demonstrated that lower MCS score was significantly associated with CKD progression (hazard ratio (HR) = 1.83, 95% CI = 1.04-3.21, P = 0.035), but that lower PCS score and RCS score were not (HR = 0.70, 95% CI = 0.39-1.25, P = 0.223; HR = 0.95, 95% CI = 0.54-1.67, P = 0.854, respectively). Conclusion We found that impaired mental health was associated with CKD progression. The evaluation of the mental health should be performed in the patients with CKD.

Background and objectives Smoking is a well known risk factor of proteinuria in adults; however, clinical studies in children are limited. The purpose of this study is to clarify the associations of maternal smoking during pregnancy and household smoking after the child’s birth with the risk of proteinuria at age 3 years old. Design, setting, participants, & measurements We performed a population–based retrospective cohort study on 44,595 children using data on prenatal health checkups, home visit neonatal health checkups, and health checkups at 4, 9, and 18 months and 3 years of age in Kobe City, Japan. Maternal smoking status (nonsmoker, past smoker, or current smoker) was collected with standardized questionnaires. The outcome of interest was the presence of proteinuria at 3 years of age defined as urinary protein ≥1+. To evaluate the association between child proteinuria and smoking status, we performed multivariate logistic regression model analyses adjusted for confounding factors. Results The prevalence rates of children in the maternal smoking groups (none, past, and current) were 78.9%, 4.4%, and 16.7%, respectively. The frequencies of child proteinuria defined as ≥1+ urinary protein were 1.7% in the current smoking group, 1.6% in the past smoking group, and 1.3% in the nonsmoking group. Maternal smoking during pregnancy was associated with child proteinuria (odds ratio, 1.24; 95% confidence interval, 1.00 to 1.52; P=0.05) in the multiple logistic regression model, although nonmaternal family smoking during pregnancy was not significantly associated with child proteinuria (odds ratio, 0.97; 95% confidence interval, 0.79 to 1.19; P=0.77). We also found a similar association with household smoking after the child’s birth (odds ratio, 1.23; 95% confidence interval, 0.99 to 1.54; P=0.06), although this observation was not significant. Conclusions Maternal smoking during pregnancy was one of the risk factors of childhood proteinuria. We also found a similar association with household smoking after the child’s birth, although this observation was not significant.

Aim To assess the diagnostic performance of lateral radiograph of the neck for supraglottitis in adults and children. Methods Electronic database searches (including PubMed, EMBASE, CINAHL, Web of Science, and WHO International Clinical Trials Registry Platform) were carried out through July 2014. Citations of included studies and recent narrative reviews were searched. Studies that compared lateral radiograph of the neck with a reference standard of direct/indirect laryngoscopy were included. Two reviewers independently assessed the methodological quality of included studies by Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Results Of 2,088 potentially relevant citations, two single-gate (cohort) studies and six two-gate (case–control) studies were identified. These included studies of design are at the moderate or high risk of bias in QUADAS-2. The pooled sensitivity from bivariate random-effects regression was 92.9% (95% confidence interval [CI], 88.5–95.9%) and the pooled specificity was 89.2% (95% CI, 85.9–91.9%), but the diagnostic value would be overestimated because of selection bias in the six two-gate studies. The sensitivity and specificity of the single-gate studies were 100.0% (95% CI, 92.2–100.0%) and 30.6% (95% CI, 15.5–35.6%) in children and 81.0% (95% CI, 78.2–93.2%) and 85.7% specificity (95% CI, 78.2–93.2%) in adults. Conclusion This study determines that there are insufficient studies of lateral neck radiograph for detecting supraglottitis. Lateral radiograph of the neck seems to have moderate accuracy for detecting supraglottitis. Further approximately unbiased studies are needed to obtain more valid and reliable estimates of test accuracy.

Background The relationship between chorioamnionitis (CAM) and neonatal mortality has been extensively investigated, but that of maternal pre-eclampsia and neonatal mortality is unclear. We investigated neonatal mortality and morbidity of maternal pre-eclampsia and clinical CAM in extremely premature infants using data from a population-based cohort study. Methods We retrospectively analyzed data obtained from the Neonatal Research Network in Japan, a population-based cohort study (n = 18 900) conducted to clarify the clinical characteristics and morbidity of very low-birthweight infants. Patients were divided into four diagnosis-based groups for comparative analysis: sole pre-eclampsia; sole clinical CAM; concurrent pre-eclampsia and clinical CAM; and non-diagnosis (of pre-eclampsia and clinical CAM). Results Mortality was higher in the pre-eclampsia groups compared with the groups without (18.3%, 84/459 vs 14.0%, 567/4059; OR, 1.38; 95%CI: 1.07-1.78). In contrast, mortality was not affected by presence of clinical CAM (with, 13.7% 182/1328 vs without, 15.0% 469/3190; OR, 0.92; 95%CI: 0.77-1.11). With regard to small for gestational age, the mortality rate increased by two-three-fold as gestational week decreased. The complication survival rate in the whole group was 35% (1135/3218). Conclusions Maternal pre-eclampsia is associated with poor prognosis in extremely premature infants. We also need to deliberate on the trade-off between the advantages of early rescue from pre-eclampsia and risk of prematurity.

Background Palliative care was a priority issue in the Cancer Control Act enacted in 2007 in Japan, and this has resulted in efforts being made toward educational goals in clinical settings. An investigation of how descriptions of palliative care for the treatment of cancer have changed in clinical practice guidelines (CPGs) could be expected to provide a better understanding of palliative care-related decision-making. This study aimed to identify trends in descriptions of palliative care in cancer CPGs in Japan before and after enactment of the Cancer Control Act. Methods Content analysis was used to count the lines in all relevant CPGs. We then compared the number of lines and the proportion of descriptions mentioning palliative care at two time points: the first survey (selection period: February to June 2007) and the second survey (selection period: February to December 2015). Descriptions from the CPGs were independently selected from the Toho University Medical Media Center and Medical Information Network Distribution Service databases, and subsequently reviewed, by two investigators. Results Descriptions were analyzed for 10 types of cancer. The proportion of descriptions in the first survey (4.4%; 933/21,344 lines) was similar to that in the second survey (4.5%; 1325/29,269 lines). Conclusions After the enactment of the Cancer Control Act, an increase was observed in the number, but not in the proportion, of palliative care descriptions in Japanese cancer CPGs. In the future, CPGs can be expected to play a major role in helping cancer patients to incorporate palliative care more smoothly.

Over the decades, the problem of postoperative recurrence of chronic subdural hematoma (CSDH) has not been resolved. The objective of our study was to investigate whether the recurrence rate of CSDH is decreased when artificial cerebrospinal fluid (ACF) is used as irrigation solution for CSDH surgery. The present study was a multi-center, prospective, randomized, open parallel group comparison test of patients enrolled from 10 hospitals in Japan. Eligible patients with CSDH were randomly assigned to undergo burr hole drainage with either normal saline (NS) or ACF irrigation. The primary end-point was postoperative recurrence of ipsilateral CSDH. A total of 402 patients with newly diagnosed CSDH were enrolled during the study period. After applying inclusion and exclusion criteria, and taking into consideration cases lost to follow-up, our final study cohorts consisted of 177 ACF patients and 165 NS patients, representing 85.7% of the initial cohort. The overall recurrence rate was 11.4%, occurring in 39 of the 342 analyzed patients during 90 days of follow-up. Recurrence rates in the ACF and NS groups were 11.9% (21 of 177) and 10.9% (18 of 165), respectively. No significant difference was evident between groups (p = 0.87). In addition, no significant difference in time to recurrence was seen between groups (p = 0.74). No serious adverse effects related to irrigation fluid were seen in either group. Regarding the irrigation fluid for CSDH surgery, no differences in recurrence rate or time to recurrence were seen between the ACF and NS groups. However, ACF offers sufficient safety as irrigation fluid for CSDH.

The clinical course of congenital neonatal sepsis due to Streptococcus pneumoniae progresses rapidly and results in multiorgan failure with high mortality. The swift progression of the disease limits the timeframe for conventional treatment, which often requires waiting for antibiotics to show efficacy. Here, we describe the case of a very low-birthweight (VLBW) female infant with congenital sepsis due to S. pneumoniae who was treated with continuous hemodiafiltration (CHDF) and polymyxin B-immobilized fiber column-direct hemoperfusion (PMX-DHP). The infant was born at 30 weeks' gestation and diagnosed with hypotension, disseminated intravascular coagulation, and pulmonary hypertension. CHDF and PMX-DHP were initiated approximately 11 h after birth. Mean blood pressure, oxygenation, and blood interleukin-6 began to improve after dialysis commencement, and the patient survived with mild sequelae. Combined CHDF and PMX-DHP may be effective in treating VLBW infants with severe septic shock.

Interstitial lung disease (ILD) is a common pulmonary manifestation of systemic sclerosis (SSc). It is unknown whether radiographic fibrosis score predicts mortality in SSc-associated ILD (SSc-ILD). We retrospectively analysed patients with SSc-ILD to evaluate whether radiographic fibrosis score was a useful predictor of mortality.We identified SSc-ILD patients evaluated at Kurashiki Central Hospital (Japan) from 2006 to 2016, and radiographic fibrosis scores based on the extent of reticulation and honeycombing on high-resolution computed tomography (HRCT) scanning were calculated by manually tracing around each fibrotic area. Independent predictors of overall survival were determined using the Cox proportional hazards model.The study included 48 patients, of whom 19 had usual interstitial pneumonia on HRCT. The median follow-up period was 56.6 months, and over the follow-up period 15 patients died. The 5-year survival was 72.4%. In the multivariate analysis, radiographic fibrosis score, age, being male and forced vital capacity were independently associated with an increased risk of death, while HRCT pattern was not.A high radiographic fibrosis score was a poor prognostic factor in SSc-ILD. More widespread fibrosis was associated with an increased risk of death, independent of HRCT pattern.

Objective To examine whether short sleep at 18 months of age is associated with risk of proteinuria at 3 years of age. Methods A population-based cohort study using municipal health check-up data from 62,623 children born between March 1, 2004, and April 30, 2011, and followed to 3 years via questionnaire in Kobe City, Japan. Sleep duration was calculated from wake time and bedtime at the 18-month health check-up by standardized parent-reported questionnaires. Proteinuria, defined as dipstick urinary protein of ≥1+, was measured by dipstick urinalysis at 3 years. Multivariable logistic regression was used to generate adjusted olds ratios. Results In total, 2253 (3.6%) children had short nighttime sleep (≤8 h) at 18 months. At 3 years, 765 (1.2%) children had proteinuria. The adjusted odds ratio for proteinuria among children with 8 h of sleep or less versus those with normal sleep of 10 h per night was 1.50 (95% confidence interval, 1.07-2.11; P = 0.02). Odds ratios of the same direction but weaker magnitude were observed for children with bedtime at 22:00 or later, and those with wake time at 6:00 or earlier. Conclusions Short sleep at 18 months was associated with risk of proteinuria at 3 years. Future research is warranted to examine whether sleep programs targeting early childhood may have additional potential health benefits for kidney development.

Background Applicability of cord blood interleukin-6 (IL-6) and interleukin-8 (IL-8) as markers for early prediction of the onset of chronic lung disease (CLD) due to intrauterine infection was investigated in the present study. Methods Eighty very low-birthweight infants with chorioamnionitis were divided into two groups: the CLD group (42 patients) and the non-CLD group (38 patients), according to the presence or absence of CLD, and the clinical background and cord blood IL-6 and IL-8 levels in each group were compared and investigated. Results The CLD group had significantly longer duration of mechanical ventilation and hospitalization (P < 0.05) and significantly higher IL-6 and IL-8 (P < 0.01) than the non-CLD group. Using the receiver operating characteristic curves of CLD onset for both IL-6 and IL-8, the cut-off value of IL-6 for predicting onset of CLD was 48.0 pg/mL, and its sensitivity and specificity were 76% and 96%, respectively. The cut-off value for IL-8 was 66.0 pg/mL, and its sensitivity and specificity were 71% and 82%, respectively. Conclusion The cord blood levels of both IL-6 and IL-8 were significantly higher in the CLD group, indicating that both IL-6 and IL-8 are useful predictors of onset of CLD.

Background: Policies to reduce methicillin-resistant Staphylococcus aureus (MRSA) infections, both healthcare-acquired (HA-MRSA) and livestock-associated (LA-MRSA) are implemented Europe-wide, but evaluations are difficult for countries yet to implement such policies. A descriptive study was conducted, describing multinational MRSA rates and policy implementation, focusing on MRSA mandatory surveillance. We also investigated antibiotic use and MRSA rates and the use of veterinary antibiotics. Methods: This study used Europe-wide surveillance data on infectious diseases (EARS-Net), antibiotic consumption (ESAC-Net), and veterinary medicine (ESVAC). We visualized LA- and HA-MRSA related policies and MRSA rates from 1999 to 2015 in seven European countries. Changes in MRSA rates after implementation of an MRSA mandatory surveillance policy were investigated by setting each country as rate of 1.0 and compared countries with and without such policy. Correlations between antibiotic use and MRSA rates from 1999 to 2012 were investigated using defined daily dose. Sales data were used to investigate veterinary antibiotic use. Results: MRSA rates were 1–45.4% across the seven countries between 1999 and 2015. MRSA rates changed between 0.61 and 0.24 after the implementation of mandatory surveillance policies within a 6–12 year span. The rate of decrease rate in implemented and non-implemented countries ranged from 10% in Spain to 76% in the UK. The correlation between MRSA rate and cephalosporin consumption was r = 0.419, and for fluoroquinolones r = 0.305. Mean annual sales of veterinary cephalosporin and quinolone antibiotics were lowest in the UK (0.8 mg/PCU) and highest in Spain (9.7 mg/PCU) between 2009 and 2014. Conclusions: There were similar but different health policy implications in the seven countries regarding LA- and HA-MRSA. Although causation could not be defined, some policies such as mandatory surveillance may be helpful for countries that have yet to implement an MRSA policy. Further investigations are needed to evaluate each policies.

Background Clinical chorioamnionitis and histological chorioamnionitis are important risk factors for neonatal complications and neurodevelopmental impairment in premature infants. It is unclear, however, whether a diagnosis of clinical chorioamnionitis is sufficient to establish a diagnosis of histological chorioamnionitis. The aim of this study was to evaluate the predictive value of clinical chorioamnionitis in the diagnosis of histological chorioamnionitis in extremely premature infants. Methods This study was a secondary analysis of data from the Neonatal Research Network in Japan, a population-based cohort study aimed at identifying the clinical characteristics and morbidity of very low-birthweight infants. Data for extremely premature infants

Background. Treatment and management strategies for asthma in children are generally consistent internationally, but prescription of antiasthma drugs differs among countries. The objective of this study was to examine the prescribing patterns of antiasthma drugs, particularly controller medications, in children. Methods. A retrospective cohort study was performed in children with asthma using an administrative claims database in Japan. Results. A total of 1149 preschool-age and 3226 school-age children were identified. Leukotriene receptor antagonists were prescribed for about 80% of the children. Long-acting β-agonists were prescribed for 87.6% and 59.6% of preschool-age and school-age children, respectively, whereas prescriptions of inhaled corticosteroids had lower rates of 8.2% and 16.5%, respectively. In an examination of prescriptions at 1-month intervals, a relatively high number of children were prescribed bronchodilators without anti-inflammatory agents. Conclusion. Our findings suggest that asthma care for children in Japan can be improved through changes in drug prescriptions.

Background Clinical guidelines assist physicians to make decisions about suitable healthcare. We conducted a controlled before-and-after study to investigate the impact of professional-led guideline workshops for patent ductus arteriosus (PDA) management on physicians’ clinical practices, discharge mortality, and associated morbid conditions among preterm neonates. Methods We recruited physicians practicing at two neonatal intensive care units (NICUs) in Japan and used the data of all neonates weighing less than or equal to 1,500 g admitted to 90 NICUs (2 intervention NICUs and 88 control NICUs) in the Neonatal Research Network of Japan from April 2008 to March 2010. We held 1-day workshops for physicians on PDA clinical practice guidelines at the two intervention NICUs. Physicians’ skills assessed by confidence rating (CR) scores and the Sheffield Peer Review Assessment Tool (SPRAT) were compared between pre- and post-workshop month at the intervention NICUs using Wilcoxon signed-rank tests. Neonatal discharge mortality and morbidity were compared between pre- and post-workshop year at both the intervention and control NICUs using multivariable regression analyses adjusting for potential confounders. Results Fifteen physicians were included in the study. Physicians’ CR scores (2.14 vs. 2.47, p = 0.02) and SPRAT (4.14 vs. 4.50, p = 0.05) in PDA management improved after the workshops. The analyses of neonatal outcomes included 294 and 6,234 neonates in the intervention and control NICUs, respectively. Neonates’ discharge mortality declined sharply at the intervention NICUs (from 15/146 to 5/148, relative risk reduction −0.67; adjusted odds ratio 0.30, 95% confidence interval 0.10 to 0.89) during the post-workshop period. The mortality reduction was much greater than that in the control NICUs (from 207/3,322 to 147/2,912, relative risk reduction −0.19; adjusted odds ratio 0.75, 95% confidence interval 0.59 to 0.95), although the difference between the intervention and control NICUs were not statistically significant. Conclusions Overall, physicians’ confidence in PDA management improved after attending guideline workshops. Face-to-face workshops by guideline developers can be a useful strategy to improve physicians’ PDA management skills and, thereby, might reduce PDA-associated mortality in preterm neonates. Electronic supplementary material The online version of this article (doi:10.1186/s13012-015-0258-5) contains supplementary material, which is available to authorized users.

The relationship between chorioamnionitis (CAM) and neonatal mortality has been extensively investigated, but that of maternal pre-eclampsia and neonatal mortality is unclear. We investigated neonatal mortality and morbidity of maternal pre-eclampsia and clinical CAM in extremely premature infants using data from a population-based cohort study.We retrospectively analyzed data obtained from the Neonatal Research Network in Japan, a population-based cohort study (n = 18 900) conducted to clarify the clinical characteristics and morbidity of very low-birthweight infants. Patients were divided into four diagnosis-based groups for comparative analysis: sole pre-eclampsia; sole clinical CAM; concurrent pre-eclampsia and clinical CAM; and non-diagnosis (of pre-eclampsia and clinical CAM).Mortality was higher in the pre-eclampsia groups compared with the groups without (18.3%, 84/459 vs 14.0%, 567/4059; OR, 1.38; 95%CI: 1.07-1.78). In contrast, mortality was not affected by presence of clinical CAM (with, 13.7% 182/1328 vs without, 15.0% 469/3190; OR, 0.92; 95%CI: 0.77-1.11). With regard to small for gestational age, the mortality rate increased by two-three-fold as gestational week decreased. The complication survival rate in the whole group was 35% (1135/3218).Maternal pre-eclampsia is associated with poor prognosis in extremely premature infants. We also need to deliberate on the trade-off between the advantages of early rescue from pre-eclampsia and risk of prematurity.

The clinical course of congenital neonatal sepsis due to Streptococcus pneumoniae progresses rapidly and results in multiorgan failure with high mortality. The swift progression of the disease limits the timeframe for conventional treatment, which often requires waiting for antibiotics to show efficacy. Here, we describe the case of a very low-birthweight (VLBW) female infant with congenital sepsis due to S. pneumoniae who was treated with continuous hemodiafiltration (CHDF) and polymyxin B-immobilized fiber column-direct hemoperfusion (PMX-DHP). The infant was born at 30 weeks' gestation and diagnosed with hypotension, disseminated intravascular coagulation, and pulmonary hypertension. CHDF and PMX-DHP were initiated approximately 11 h after birth. Mean blood pressure, oxygenation, and blood interleukin-6 began to improve after dialysis commencement, and the patient survived with mild sequelae. Combined CHDF and PMX-DHP may be effective in treating VLBW infants with severe septic shock.

Applicability of cord blood interleukin-6 (IL-6) and interleukin-8 (IL-8) as markers for early prediction of the onset of chronic lung disease (CLD) due to intrauterine infection was investigated in the present study.Eighty very low-birthweight infants with chorioamnionitis were divided into two groups: the CLD group (42 patients) and the non-CLD group (38 patients), according to the presence or absence of CLD, and the clinical background and cord blood IL-6 and IL-8 levels in each group were compared and investigated.The CLD group had significantly longer duration of mechanical ventilation and hospitalization (P0.05) and significantly higher IL-6 and IL-8 (P0.01) than the non-CLD group. Using the receiver operating characteristic curves of CLD onset for both IL-6 and IL-8, the cut-off value of IL-6 for predicting onset of CLD was 48.0 pg/mL, and its sensitivity and specificity were 76% and 96%, respectively. The cut-off value for IL-8 was 66.0 pg/mL, and its sensitivity and specificity were 71% and 82%, respectively.The cord blood levels of both IL-6 and IL-8 were significantly higher in the CLD group, indicating that both IL-6 and IL-8 are useful predictors of onset of CLD.

Background A major cause of failure to achieve spontaneous vaginal birth is delay in labour due to presumed inefficient uterine action. Oxytocin is given to increase contractions and high-dose regimens may potentially increase the number of spontaneous vaginal births, but as oxytocin can cause hyperstimulation of the uterus, there is a possibility of increased adverse events. Objectives To compare starting dose and increment dose of oxytocin for augmentation for women delayed in labour to determine whether augmentation by high-dose regimens of oxytocin improves labour outcomes and to examine the effect on both maternal/neonatal outcomes and women's birth experiences. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013) and reference lists of retrieved studies. Selection criteria We included all randomised and quasi-randomised controlled trials for women in delayed labour requiring augmentation by oxytocin comparing high-dose regimens (defined as starting dose and increment of equal to or more than 4 mU per minute) with low-dose regimens (defined as starting dose and an increment of less than 4 mU per minute). Increase interval: between 15 and 40 minutes. The separation of low- and high-dose regimens is based on an arbitrary decision. Data collection and analysis Four review authors undertook assessment of trial eligibility, risk of bias, and data extraction independently. Main results We included four studies involving 644 pregnant women. Three studies were randomised controlled trials and one trial was a quasi-randomised study. A higher dose of oxytocin was associated with a significant reduction in length of labour reported from one trial (mean difference (MD) -3.50 hours; 95% confidence interval (CI) -6.38 to -0.62; one trial, 40 women). There was a decrease in the rate of caesarean section (risk ratio (RR) 0.62; 95% CI 0.44 to 0.86 four trials, 644 women) and an increase in the rate of spontaneous vaginal birth in the high-dose group (RR 1.35; 95% CI 1.13 to 1.62, three trials, 444 women), although for both of these outcomes there were inconsistencies between studies in the size of effect. When we carried out sensitivity analysis (temporarily removing a study at high risk of bias) the differences between groups were no longer statistically significant There were no significant differences between high- and low-dose regimens for instrumental vaginal birth, epidural analgesia, hyperstimulation, postpartum haemorrhage, chorioamnionitis or women's perceptions of experiences. For neonatal outcomes, there was no significant difference between groups for Apgar scores, umbilical cord pH, admission to special care baby unit, or neonatal mortality. The following outcomes were not evaluated in the included studies: perinatal mortality, uterine rupture, abnormal cardiotocography, women's pyrexia, dystocia and neonatal neurological morbidity. Authors' conclusions Higher-dose regimens of oxytocin (4 mU per minute or more) were associated with a reduction in the length of labour and in caesarean section, and an increase in spontaneous vaginal birth. However, there is insufficient evidence to recommend that high-dose regimens are advised routinely for women with delay in the first stage of labour. Further research should evaluate the effect of high-dose regimens of oxytocin for women delayed in labour and should include maternal and neonatal outcomes as well as the effects on women.

Clinical chorioamnionitis and histological chorioamnionitis are important risk factors for neonatal complications and neurodevelopmental impairment in premature infants. It is unclear, however, whether a diagnosis of clinical chorioamnionitis is sufficient to establish a diagnosis of histological chorioamnionitis. The aim of this study was to evaluate the predictive value of clinical chorioamnionitis in the diagnosis of histological chorioamnionitis in extremely premature infants.This study was a secondary analysis of data from the Neonatal Research Network in Japan, a population-based cohort study aimed at identifying the clinical characteristics and morbidity of very low-birthweight infants. Data for extremely premature infants28 weeks' gestational age from 2003 to 2007, were used. Subset analysis investigated positive predictive value by gestational age.Of the 2470 infants analyzed, 786 were diagnosed with clinical chorioamnionitis and 1129 with histological chorioamnionitis. The positive predictive value of clinical chorioamnionitis for histological chorioamnionitis was 86.6% (681/786; 95% confidence interval [CI]: 84.4-88.6%), sensitivity was 60.3% (681/1129; 95%CI: 58.8-61.7%), and specificity was 92.2% (1236/1341; 95%CI: 90.9-93.3%). In subset analysis, the positive predictive value was particularly high at 23 weeks of gestation (89.1%; 115/129), with sensitivity of 65.3% (115/176) and specificity of 89.6% (120/134).The finding that clinical chorioamnionitis is a useful predictor of histological chorioamnionitis provides important insights into the relationship between these two diagnoses, and has important implications in determining the appropriate timing of delivery of extremely premature infants.

A major cause of failure to achieve spontaneous vaginal birth is delay in labour caused by presumed inefficient uterine action. High dose may potentially increase the number of spontaneous vaginal births, but as oxytocin can cause hyperstimulation of the uterus, there is a possibility of increased adverse events.To compare starting dose and increment of amount of oxytocin for augmentation for women delayed in labour to determine whether augmentation by high dose of oxytocin improves labour outcomes and the effect on both maternal/neonatal outcomes and women's birth experiences.We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 February 2011) and reference lists of retrieved studies.We included all randomised and quasi-randomised controlled trials for women in delayed in labour requiring augmentation by oxytocin comparing high starting and increment dose (defined as starting dose and increment of equal to or more than 4 mU per minute) with low dose (defined as starting dose and an increment of less than 4 mU per minute. Increase interval: between 15 and 40 minutes. The separation of low and high doses is based on an arbitrary decision.Three review authors undertook assessment of trial eligibility, risk of bias, and data extraction independently.We included four studies involving 660 pregnant women. Three studies were randomised controlled trials and one trial was a quasi-randomised study. A higher dose of oxytocin was associated with a significant reduction in length of labour reported from one trial (mean difference (MD) -3.50 hours; 95% confidence interval (CI) -6.38 to -0.62; one trial, 40 women). There was a decrease in rate of caesarean section (risk ratio (RR) 0.53; 95% CI 0.38 to 0.75, four trials, 650 women) and an increase in the rate of spontaneous vaginal birth (RR 1.37; 95% CI 1.15 to 1.64, two trials, 350 women). There were no significant differences for neonatal mortality, hyperstimulation, chorioamnionitis, epidural analgesia; or neonatal outcomes of Apgar scores, umbilical cord pH or admission to special care baby unit. The following outcomes were not evaluated in the included studies: perinatal mortality, women's satisfaction, instrumental vaginal birth, uterine rupture, postpartum haemorrhage, abnormal cardiotocography, women's pyrexia, dystocia and neonatal neurological morbidity.Higher dose of oxytocin starting and increment dose (4 mU per minute or more) was associated with a reduction in the length of labour and in caesarean section, and an increase in spontaneous vaginal birth. However, there is insufficient evidence. The number of studies and the quality of the available evidence is of concern. Additionally, there is insufficient evidence for other maternal and neonatal outcomes, and how women feel about the higher doses of oxytocin. Therefore, no firm recommendation can be made. Further research should evaluate the effect of high dose oxytocin for women delayed in labour and should include these outcomes.

Study question Does maternal smoking during pregnancy and exposure of infants to tobacco smoke at age 4 months increase the risk of caries in deciduous teeth? Methods Population based retrospective cohort study of 76 920 children born between 2004 and 2010 in Kobe City, Japan who received municipal health check-ups at birth, 4, 9, and 18 months, and 3 years and had information on household smoking status at age 4 months and records of dental examinations at age 18 months and 3 years. Smoking during pregnancy and exposure of infants to secondhand smoke at age 4 months was assessed by standardised parent reported questionnaires. The main outcome measure was the incidence of caries in deciduous teeth, defined as at least one decayed, missing, or filled tooth assessed by qualified dentists without radiographs. Cox regression was used to estimate hazard ratios of exposure to secondhand smoke compared with having no smoker in the family after propensity score adjustment for clinical and lifestyle characteristics. Study answer and limitations Prevalence of household smoking among the 76 920 children was 55.3% (n=42 525), and 6.8% (n=5268) had evidence of exposure to tobacco smoke. A total of 12 729 incidents of dental caries were observed and most were decayed teeth (3 year follow-up rate 91.9%). The risk of caries at age 3 years was 14.0% (no smoker in family), 20.0% (smoking in household but without evidence of exposure to tobacco smoke), and 27.6% (exposure to tobacco smoke). The propensity score adjusted hazard ratios of the two exposure groups compared with having no smoker in the family were 1.46 (95% confidence interval 1.40 to 1.52) and 2.14 (1.99 to 2.29), respectively. The propensity score adjusted hazard ratio between maternal smoking during pregnancy and having no smoker in the family was 1.10 (0.97 to 1.25). What this study adds Exposure to tobacco smoke at 4 months of age was associated with an approximately twofold increased risk of caries, and the risk of caries was also increased among those exposed to household smoking, by 1.5-fold, whereas the effect of maternal smoking during pregnancy was not statistically significant. Funding, competing interests, data sharing This study was supported by a grant in aid for scientific research 26860415. The authors have no competing interests or additional data to share.