園芸学部研究業績紹介(目次)

<p>Multivariable analysis to determine prognostic factors for surgical failure of 2^nd operated trabeculectomy using Cox proportional hazards regression models among the successful 1^st operated eyes.</p

Plasma Citrate Levels Are Associated with an Increased Risk of Cardiovascular Mortality in Patients with Type 2 Diabetes (Zodiac-64)

Circulating citrate may represent a proxy of mitochondrial dysfunction which plays a role in the development of vascular complications in type 2 diabetes (T2D). Here, we determined the associations between plasma citrate levels and cardiovascular (CV) mortality in T2D patients. In this prospective cohort study, 601 patients were included who participated in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC). Plasma citrate levels were measured by nuclear magnetic resonance spectroscopy. Cox proportional hazards regression models were used to evaluate the associations between plasma citrate and the risk of CV mortality. Over a median follow-up of 11.4 years, 119 (19.8%) of the 601 patients died from a CV cause. In multivariable Cox proportional hazards regression models, adjusting for conventional risk factors, plasma citrate was associated with an increased risk of CV mortality (the hazard ratio (HR) per 1-SD increment was 1.19 (95%CI: 1.00–1.40), p = 0.048). This association was prominent in males (n = 49 with CV mortality) (HR 1.52 (95%CI: 1.14–2.03), p = 0.005), but not in females (n = 70 with CV mortality) (HR 1.11 (95%CI: 0.90–1.37), p = 0.319) (age-adjusted Pinteraction = 0.044). In conclusion, higher plasma citrate levels are associated with an increased risk of CV mortality in patients with established T2D. Future studies are warranted to unravel the potential role of citrate-related pathways in the pathogenesis of T2D-related vascular complications

Low oxygen saturation and mortality in an adult cohort; the Tromsø Study

Published version, also available at http://dx.doi.org/10.1186/s12890-015-0003-5Background: Oxygen saturation has been shown in risk score models to predict mortality in emergency medicine. The aim of this study was to determine whether low oxygen saturation measured by a single-point measurement by pulse oximetry (SpO2) is associated with increased mortality in the general adult population. Methods: Pulse oximetry was performed in 5,152 participants in a cross-sectional survey in Tromsø, Norway, in 2001–2002 (“Tromsø 5”). Ten-year follow-up data for all-cause mortality and cause of death were obtained from the National Population and the Cause of Death Registries, respectively. Cause of death was grouped into four categories: cardiovascular disease, cancer except lung cancer, pulmonary disease, and others. SpO2 categories were assessed as predictors for all-cause mortality and death using Cox proportional-hazards regression models after correcting for age, sex, smoking history, body mass index (BMI), C-reactive protein level, self-reported diseases, respiratory symptoms, and spirometry results. Results: The mean age was 65.8 years, and 56% were women. During the follow-up, 1,046 (20.3%) participants died. The age- and sex-adjusted hazard ratios (HRs) (95% confidence intervals) for all-cause mortality were 1.99 (1.33–2.96) for SpO2 ≤ 92% and 1.36 (1.15–1.60) for SpO2 93–95%, compared with SpO2 ≥ 96%. In the multivariable Cox proportional-hazards regression models that included self-reported diseases, respiratory symptoms, smoking history, BMI, and CRP levels as the explanatory variables, SpO2 remained a significant predictor of all-cause mortality. However, after including forced expiratory volume in 1 s percent predicted (FEV1% predicted), this association was no longer significant. Mortality caused by pulmonary diseases was significantly associated with SpO2 even when FEV1% predicted was included in the model. Conclusions: Low oxygen saturation was independently associated with increased all-cause mortality and mortality caused by pulmonary diseases. When FEV1% predicted was included in the analysis, the strength of the association weakened but was still statistically significant for mortality caused by pulmonary diseases

Association of Total and Differential White Blood Cell Counts to Development of Type 2 Diabetes in Mexican Americans in Cameron County Hispanic Cohort

Objective: To evaluate the relationship between total and differential White Blood Cell (WBC) counts with time to transition to type 2 diabetes in Mexican Americans using prospective data from the Cameron County Hispanic Cohort (CCHC). Results: Multivariable Cox proportional hazards regression models revealed that obese Mexican-American cohort participants whose total WBC or granulocyte count increased over time had 1.39 and 1.35 times higher risk respectively of transition to type 2 diabetes when compared to overweight participants. The granulocyte or total WBC count in participants with BMI≥35 were significant risk factors for transition to type 2 diabetes. Conclusions: Increased total WBC and WBC differential counts, particularly lymphocytes and granulocytes, are associated with risk of transition to type 2 diabetes in obese Mexican Americans, after adjusting for other potential confounders. Screening and monitoring the WBC counts, including lymphocytes and granulocytes can help with monitoring potential transition to type 2 diabetes

Comparison of the efficacy of half ticagrelor loading doses and clopidogrel in elderly acute coronary syndrome patients in China

Purpose: To evaluate the effects of half-load doses (HLD) of ticagrelor and clopidogrel on elderly acute coronary syndrome patients (ACS) over a period of 90 days. Methods: Seventy-four patients diagnosed as ACS were included in this trial. The patients were randomly distributed into group 1 (treated with HLD ticagrelor, 90 mg LD) and group 2 (treated with clopidogrel, 300 mg LD). The interaction of treatment effect was evaluated using Multivariate Cox proportional hazards regression models. Results: Within three months, a total of 12 patients (16.21 %) died of myocardial infarction or stroke. The endpoint of HLD ticagrelor-treated elderly ACS patients was 20 %, and the incidence of clopidogreltreated endpoints was 14.81 %. Conclusion: In the first 45 patients treated with HLD ticagrelor, their cumulative incidence of cardiac events was relatively high. However, there were no considerable changes in the therapeutic benefits of these two drugs in elderly ACS patients. Keywords: Elder patients, Acute coronary syndrome, Ticagrelor, Clopidogre

The Effect of Ignoring Statistical Interactions in Regression Analyses Conducted in Epidemiologic Studies: An Example with Survival Analysis Using Cox Proportional Hazards Regression Model

Objective: To demonstrate the adverse impact of ignoring statistical interactions in regression models used in epidemiologic studies. Study design and setting: Based on different scenarios that involved known values for coefficient of the interaction term in Cox regression models we generated 1000 samples of size 600 each. The simulated samples and a real life data set from the Cameron County Hispanic Cohort were used to evaluate the effect of ignoring statistical interactions in these models. Results: Compared to correctly specified Cox regression models with interaction terms, misspecified models without interaction terms resulted in up to 8.95 fold bias in estimated regression coefficients. Whereas when data were generated from a perfect additive Cox proportional hazards regression model the inclusion of the interaction between the two covariates resulted in only 2% estimated bias in main effect regression coefficients estimates, but did not alter the main findings of no significant interactions. Conclusions: When the effects are synergic, the failure to account for an interaction effect could lead to bias and misinterpretation of the results, and in some instances to incorrect policy decisions. Best practices in regression analysis must include identification of interactions, including for analysis of data from epidemiologic studies

Visualizing the (Causal) Effect of a Continuous Variable on a Time-To-Event Outcome

Visualization is a key aspect of communicating the results of any study aiming to estimate causal effects. In studies with time-to-event outcomes, the most popular visualization approach is depicting survival curves stratified by the variable of interest. This approach cannot be used when the variable of interest is continuous. Simple workarounds, such as categorizing the continuous covariate and plotting survival curves for each category, can result in misleading depictions of the main effects. Instead, we propose a new graphic, the survival area plot, to directly depict the survival probability over time and as a function of a continuous covariate simultaneously. This plot utilizes g-computation based on a suitable time-to-event model to obtain the relevant estimates. Through the use of g-computation, those estimates can be adjusted for confounding without additional effort, allowing a causal interpretation under the standard causal identifiability assumptions. If those assumptions are not met, the proposed plot may still be used to depict noncausal associations. We illustrate and compare the proposed graphics to simpler alternatives using data from a large German observational study investigating the effect of the Ankle Brachial Index on survival. To facilitate the usage of these plots, we additionally developed the contsurvplot R-package which includes all methods discussed in this paper.Comment: currently under review in "Epidemiology

Effect of individual-level and socioeconomic factors on long-term survival after cataract surgery over a 30-year period

Purpose: To evaluate survival and the risk for mortality after cataract surgery in relation to individual-level and socioeconomic factors in Scotland over 3 decades. Setting: Linked healthcare data, United Kingdom. Design: Representative population-based study. Methods: A 5% random sample of Scottish decedents linked to hospital records (1981 to 2012) was assessed. Survival time, survival probability, and determinants of mortality were evaluated after the first and second recorded hospital episodes for cataract surgery. Cox proportional-hazards regression models were used to assess the effect of individual-level and socioeconomic factors including age, geographic location, socioeconomic status, and comorbidity on mortality. Results: The study evaluated linked administrative healthcare data from 9228 deceased patients who had cataract surgery. The mean survival time was 2383 days ± 1853 (SD). The survival probability decreased from 98% 90 days after surgery to 22% at 10 years, 2% at 20 years, and 0% after 30 years. The mean age was 77 ± 9 years. Age (hazard ratio [HR] 3.66; 95% confidence interval [CI], 2.97-3.80; P &#60; .001) and severe comorbidity (HR 1.68; 95% CI, 1.47-1.91; P &#60; .001) were associated with an increased risk for mortality; women had a 20% lower risk than men (HR 0.80; 95% CI, 0.76-0.83; P &#60; .001). Socioeconomic status and rural geographic locations were not linked to mortality. Conclusions: Long-term survival after cataract surgery was determined by individual-level characteristics reflecting the mortality patterns of aging populations. The mortality risk was independent of socioeconomic and geographic factors per se

Differentiated Thyroid Cancer in Navarra (Spain): Historic Cohort Results (1987–2003)

Introduction. Navarra has the highest incidence of differentiated thyroid cancer in Spain. The aim of this study was to review its management carried out by the Navarra's multidisciplinary Thyroid Disease Unit, from 1987 to 2003. Material and Methods. 325 patients were studied to find the incidence, prevalence, and prognostic factors. Statistical analysis comprised univariate and multivariate Cox proportional hazards regression models for survival and tumor recurrence. Results. The average annual incidence was 3.6 per 100,000 inhabitants, with a final prevalence of 82.4 per 100,000. Regarding survival and recurrence, statistical significance was observed for stage IV, follicular carcinoma, capsular and prethyroid muscles invasion, and T4 group. Only survival was related to tumour size larger than 40 mm. Only recurrence was related to lymph node metastases and radioiodine dose higher than 100 mCi. Conclusions. Attendance of patients in a functional unit setting has allowed us to classify them into three risk groups