Background: In case-cohort studies with binary outcomes, ordinary logistic regression analyses have been widely used because of their computational simplicity. However, the resultant odds ratio ...estimates cannot be interpreted as relative risk measures unless the event rate is low. The risk ratio and risk difference are more favorable outcome measures that are directly interpreted as effect measures without the rare disease assumption.Methods: We provide pseudo-Poisson and pseudo-normal linear regression methods for estimating risk ratios and risk differences in analyses of case-cohort studies. These multivariate regression models are fitted by weighting the inverses of sampling probabilities. Also, the precisions of the risk ratio and risk difference estimators can be improved using auxiliary variable information, specifically by adapting the calibrated or estimated weights, which are readily measured on all samples from the whole cohort. Finally, we provide computational code in R (R Foundation for Statistical Computing, Vienna, Austria) that can easily perform these methods.Results: Through numerical analyses of artificially simulated data and the National Wilms Tumor Study data, accurate risk ratio and risk difference estimates were obtained using the pseudo-Poisson and pseudo-normal linear regression methods. Also, using the auxiliary variable information from the whole cohort, precisions of these estimators were markedly improved.Conclusion: The ordinary logistic regression analyses may provide uninterpretable effect measure estimates, and the risk ratio and risk difference estimation methods are effective alternative approaches for case-cohort studies. These methods are especially recommended under situations in which the event rate is not low.
The processes of tsunami inundation, sediment transport, and deposition on coastal lowlands are investigated experimentally. We conducted large-scale experiments with land slopes of 0.00 and 0.01 and ...compared them with experiments conducted previously with a slope of 0.02. The ratio of marine-originated sediment in the inland deposits decreased as the land slope decreased, reflecting the strong inundation flow and weak return flow. The sediment concentration near the bed increased remarkably and supplied a greater quantity of coarse sand inland when the land slope decreased, indicating the strong influence of land slope on bed load. The extent of sandy deposits and the inundation limit nearly corresponded with the sloping topographies. However, the inundation flow reached much farther inland than the sandy deposits on the flat (i.e., level) topography. This was because the extent of sandy deposits was determined by the flow speed, which depended in turn on the wave speed, whereas the inundation limit was determined by the inland water mass, which depended in turn on the waveform. The floating load reached the inundation limit and formed very thin and sparse muddy deposits. Considering the uncertainty of the waveform and the difficulty of detecting muddy deposits, it is more feasible to estimate the wave speed from the extent of sandy deposits. The spatial distributions of sandy deposits for various waves, land slopes, and topographies were characterized by the nondimensional area density and inundation distance. This result suggested the possibility of quantitative comparison among field investigations of tsunami deposits under various conditions. The formation of an inverse grading layer, experimentally observed in a wide range of inland deposits, was attributed to kinetic sieving. The bed load under slow deposition was speculated to thicken the inverse grading layer by reworking the coarse sand. Additionally, the sediment behind dunes became liquefied and showed shear deformation during the erosion. The shear deformation of liquefied sediment below the erosional surface might leave sedimentary characteristics specific to earthquake tsunamis.
•TSTLE project reproduced tsunami deposits on land slopes of 0.00–0.01.•Bed slope strongly affects the amount of bed load.•Inverse grading was attributed to kinetic sieving.•Flow distance can be a better parameter for reconstructing the wave scale.•Shear deformation of liquefied sediments might be evidence of earthquake tsunamis.
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.
Background: This cohort study aimed to estimate incidence rates of femoral shaft fracture in patients who were treated with antiresorptive drugs.Methods: We used data from the National Database of ...Health Insurance Claims of Japan from April 2009 and October 2016. All patients with new use of an antiresorptive drug, prescription-free period of ≥3 months, and no prior femoral fractures were included. Femoral shaft fractures were identified using a validated definition based on International Classification of Diseases, 10th revision (ICD-10) codes. Incidence rate ratios were estimated using Poisson regression, with adjustment for sex, age, and the Charlson Comorbidity Index.Results: We identified 7,958,655 patients (women: 88.4%; age ≥75 years: 51.2%). Femoral shaft fractures were identified in 22,604 patients. Incidence rates per 100,000 person-years were 74.8 for women, 30.1 for men, 30.1 for patients aged ≤64 years, 47.7 for patients aged 65–74 years, and 99.0 for patients aged ≥75 years. Adjusted incidence rate ratios in patients taking versus not taking each type of antiresorptive drug were 1.00 (95% confidence interval CI, 0.98–1.03) for bisphosphonates, 0.46 (95% CI, 0.44–0.48) for selective estrogen receptor modulators, 0.24 (95% CI, 0.18–0.32) for estrogens, 0.75 (95% CI, 0.71–0.79) for calcitonins, and 0.93 (95% CI, 0.84–1.03) for denosumab. The adjusted incidence rate ratio for alendronate was 1.18 (95% CI, 1.14–1.22).Conclusion: The incidence rates of femoral shaft fracture varied across patients treated with different antiresorptive drugs. Further research on a specific antiresorptive drug can increase understanding of the risk of femoral shaft fracture.
Placebo effect is one of the methodological difficulties in dry eye clinical trials. If we could elucidate the tendencies of the placebo response and find predictors, we could reduce the placebo ...response in clinical trials for dry eye. In this study, we investigated the predictive factors for the placebo effect in dry eye clinical trials.
A total of 205 patients with dry eye assigned to the placebo arms of three placebo-controlled randomised clinical trials were analysed by simple and multivariable regression analysis. The corneal fluorescein (FL) staining score and dry eye symptoms were studied at week 4. The variables of interest included gender, age, complications of Sjögren's syndrome, Schirmer's test I value, tear break-up time and conjunctival hyperaemia score. We also conducted a stratified analysis according to the patients' age.
Among all the studied endpoints, the baseline scores were significantly related to the corresponding placebo response. In addition, for the FL score and the dryness score, age was a significant predictor of the placebo response (p=0.04 and p<0.0001, respectively). Stratified analysis by age showed that patients more than 40 years of age are more likely to have a stronger placebo response in the FL and dryness scores.
The baseline scores and age were predictive factors of the placebo response in frequently used endpoints, such as FL score or dryness symptoms. These patient characteristics can be controlled by study design, and our findings enable the design of more efficient placebo-controlled studies with good statistical power.
To evaluate whether or not the urinary pentosidine level has clinical value in the assessment of the osteoporotic fracture risk, a novel ELISA for pentosidine was used in clinical samples. This study ...employed a cross-sectional design to analyze a subset of postmenopausal women in the Nagano Cohort Study. A total of 517 urine samples were analyzed using an ELISA system, which can measure urinary pentosidine without hydrolysis. Patients were asked about their history of non-vertebral osteoporotic fracture and the prevalence of vertebral fracture was semi-quantitatively assessed on X-ray films. A 10-year increase in age was related to a 1.09-fold increase in the urinary pentosidine level (95% CI 1.05–1.13,
P
< 0.001), prevalent fracture (+) was related to a 1.10-fold increase in the urinary pentosidine level (95% CI 1.03–1.18,
P
= 0.006). Patients with prevalent fracture who had a normal bone mineral density (BMD) showed higher pentosidine levels (median 34.3 pM/mg Cr) than patients with a low BMD without fracture (median 31.4 pM/mg Cr). A multivariable logistic regression analysis revealed that urinary pentosidine was significantly associated with the prevalence of fracture after adjustment for known risk factors for fracture (odds ratio 1.92, 95% CI 1.09–3.37,
P
= 0.023). The present results indicated a significant association between urinary pentosidine and fracture after adjustment for age and BMD, suggesting that urinary pentosidine may be useful for assessing the fracture risk in postmenopausal women.
To examine whether late bedtime and short nighttime sleep duration at age 18 months are associated with risk of caries in deciduous teeth.
Population-based cohort study using health check-up data of ...71 069 children born in Kobe City, Japan, who were free of caries at age 18 months and had information on sleep variables at age 18 months and records of dental examinations at age 3 years. Sleep variables were assessed by standardized parent-reported questionnaires, and the incidence of caries in deciduous teeth was defined as the occurrence of at least 1 decayed, missing, or filled tooth assessed by qualified dentists without radiographs. Logistic regression was used to estimate the effects of late bedtime and short sleep duration on dental caries with adjustment for clinical and lifestyle characteristics.
Overall, 11 343 (16.0%) cases of caries were observed at age 3 years. aORs for children with late or irregular bedtimes compared with those with bedtimes before 21:00 were 1.26 (95% CI 1.19-1.33), 1.48 (1.38-1.58), 1.74 (1.58-1.92), 1.90 (1.58-2.29), and 1.66 (1.53-1.81) for bedtimes at 21:00, 22:00, 23:00, 0:00, and irregular bedtime, respectively. aORs for children with short or irregular sleep duration compared with those with sleep duration of ≥11 hours were 1.30 (95% CI 1.15-1.47), 1.16 (1.09-1.24), 1.11 (1.05-1.18), and 1.35 (1.25-1.46) for sleep duration of ≤ 8, 9, 10 hours, and irregular sleep duration, respectively.
In this exploratory study, late bedtime and short sleep duration were both consistently associated with increased risk of caries in deciduous teeth.
Aim
Six‐month recipient mortality after adult‐to‐adult living‐donor liver transplantation (LDLT) remains high. Early and accurate prediction of recipient outcome and continuous monitoring of ...recipient severity after surgery are both essential for guiding appropriate care. This study was designed to identify early post‐transplant parameters associated with 6‐month mortality, and thereby to construct a discriminatory prognostic index (PI).
Methods
We retrospectively analyzed 400 consecutive primary adult‐to‐adult LDLTs in our center (2006–2017). Perioperative variables were comprehensively analyzed for their accuracy in predicting recipient mortality by comparing the area under the receiver operating characteristic (AUROC) of each factor.
Results
The AUROCs of preoperative predictive factors, for example, Model for End‐stage Liver Disease (MELD) score and donor age, were 0.56 and 0.64, respectively, whereas those of post‐transplant platelet count (PLT), total bilirubin (T‐BIL), and prothrombin time – international normalized ratio (INR) on postoperative day (POD)‐7−14 were 0.71/0.84, 0.68/0.82, and 0.71/0.78, respectively. Logistic regression analysis provided a formula: PIPOD‐14 = 3.39 + 0.12 × PLTPOD‐14 − 0.09 × T‐BILPOD‐14 − 1.23 × INRPOD‐14, indicating a high AUROC of 0.87. Recipient 6‐month survival with PIPOD‐14 < 2.38 (n = 173) was 71.7%, whereas that with PIPOD‐14 ≥ 2.38 (n = 222) was 97.7% (P < 0.001). The AUROCs of PIPOD‐7 were as high as 0.8 in the subgroups with younger donors (<50 years of age), right lobe grafts, ABO‐identical/compatible combinations, or low MELD score (<20), indicating usefulness of PI to identify unexpectedly complicated cases within the first week.
Conclusions
A novel, post‐transplant survival estimator, PI, accurately predicts recipient 6‐month mortality within 1–2 weeks after adult LDLT. Daily monitoring of PI could facilitate early interventions including retransplantation in critically ill patients.
Vonoprazan, a potassium-competitive acid blocker, is expected to be superior to proton pump inhibitors (PPIs) in preventing post-endoscopic submucosal dissection (ESD)-induced gastric bleeding. ...However, the results of randomized controlled trials (RCTs) and observational studies on the efficacy of vonoprazan have been inconsistent. This study aimed to evaluate the effectiveness of vonoprazan in antithrombotic drug users, a population that has been excluded from RCTs. Treatment effects were assessed using cross-design synthesis, which can be adjusted for differences in study design and patient characteristics. We used data from an RCT in Japan (70 patients in the vonoprazan group and 69 in the PPI group) and an observational study (408 patients in the vonoprazan group and 870 in the PPI group). After matching, among the antithrombotic drug users in the observational study, post-ESD bleeding was noted in 8 out of 86 patients in the vonoprazan group and 18 out of 86 patients in the PPI group. After pooling the data from the RCT and observational study, the risk difference for antithrombotic drug users was -14.6% (95% CI: -22.0 to -7.2). CDS analysis suggested that vonoprazan is more effective than PPIs in preventing post-ESD bleeding among patients administered antithrombotic medications.
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