Multiple Cox Proportional Hazards Models Research Articles

Critical windows for maternal fine particulate matter exposure and adverse birth outcomes: The Shanghai birth cohort study

BackgroundPrenatal exposure to ambient levels of air pollution has been reported to adversely affect birth outcomes, yet few studies have investigated refined susceptible windows for adverse birth outcomes. ObjectivesThe study aimed at estimating associations between maternal exposure to ambient fine particulate matter (PM2.5; particles with an aerodynamic diameter ≤ 2.5 μm) and birth outcomes, including birth weight, low birth weight (LBW) and preterm birth (PTB), and identify specific susceptible windows. MethodsA total of 3692 singleton live births were enrolled between 2013 and 2016 in Shanghai Birth Cohort, China. Based on mothers’ residential addresses, weekly mean concentrations of PM2.5 over gestation were estimated based on an incorporated evaluating approach combining satellite-based estimates and ground-level measurements. Distributed lag non-liner models (DLNMs) were fitted by incorporating with multiple liner models and Cox proportional hazard models to evaluate weekly-as well as trimester-exposure-lag-response associations between average PM2.5 level and birth weight, LBW and PTB, and to identify critical windows. ResultsIn this study, gestational exposure to PM2.5 was associated with adverse birth outcomes in infants, and critical windows were identified as 31st–34th gestational weeks for reduced birth weight, 38th–42 nd weeks for LBW and 27th–30th weeks for PTB, respectively. Trimester-specific associations were found for all birth outcomes during the third trimester. ConclusionsAmbient PM2.5 exposure exhibited adverse impacts on multiple outcomes including reduced birth weight, LBW and PTB in the late pregnancy. The study provides further evidence supporting harmful effects of maternal PM2.5 exposure on birth outcomes and identifying critical windows.

The Impact of Coronary Artery Disease and Statins on Survival After Liver Transplantation.

Cardiovascular disease (CVD) is a major contributor to longterm mortality after liver transplantation (LT) necessitating aggressive modification of CVD risk. However, it is unclear how coronary artery disease (CAD) and the development of dyslipidemia following LT impacts clinical outcomes and how management of these factors may impact survival. Patients undergoing LT at Virginia Commonwealth University from January 2007 to January 2017 were included (n=495). CAD and risk factors in all potential liver transplantation recipients (LTRs) over the age of 50years were evaluated via coronary angiography. The impact of pre-LT CAD after transplantation was evaluated via a survival analysis. Additionally, factors associated with new-onset dyslipidemia, statin use, and mortality were assessed using multiple logistic regression or Cox proportional hazards models. The mean age of the cohort was 55.3±9.3years at the time of LT, and median follow-up was 4.5years. CAD was noted in 129 (26.1%) patients during the pre-LT evaluation. The presence or severity of pre-LT CAD did not impact post-LT survival. Dyslipidemia was present in 96 patients at LT, and 157 patients developed new-onset dyslipidemia after LT. Statins were underused as only 45.7% of patients with known CAD were on therapy. In patients with new-onset dyslipidemia, statin therapy was initiated in 111 (71.1%), and median time to initiation of statin therapy was 2.5years. Statin use conferred survival benefit (hazard ratio, 0.25; 95% confidence interval, 0.12-0.49) and was well tolerated with only 12% of patients developing an adverse event requiring the cessation of therapy. In conclusion, pre-LT CAD did not impact survival after LT, potentially suggesting a role of accelerated atherosclerosis that may not be captured on pre-LT testing. Although statin therapy confers survival benefit, it is underused in LTRs.

Periodontal Pathogens and Their Association with Incident All-Cause and Alzheimer's Disease Dementia in a Large National Survey

Background: Infectious agents including periodontal pathogens and their neuroinflammatory sequelae have been at the forefront of Alzheimer's Disease (AD) pathology. We investigated whether periodontal disease (Pd) markers and periodontal pathogens in mid-life are associated with clinical outcomes of cognitive impairment after decades of follow-up. Methods: We conducted a retrospective cohort analysis using data from the third National Health and Nutrition Examination Surveys (NHANES III) linked with restricted mortality and incident outcomes derived from the National Death Index and Medicare data [≥45y, 43% men, Nmax=6,650, 1988-1994 through January 1st, 2014, mean follow-up times (45+, all outcomes): 15-17y]. Outcomes of interest included AD mortality (nmax=102), incidence of AD (nmax=888) and all-cause dementia (nmax=1,737). Exposures included Pd markers [mean clinical attachment loss (CAL) and Probing Depth (PD)] and 19 periodontal pathogens (1988-1994: k=19; 1991-1994 (phase 2): k=2). Multiple Cox proportional hazards models were conducted, stratified by age and sex. Findings: In those ≥65 years old, AD incidence was associated with a composite factor comprised of C. Rectus and P. Gingivalis (Pg) titers (per SD, aHR=1.22; 95% CI, 1.04-1.43, P=0.012), whereas AD mortality risk increased with higher baseline levels in a factor comprised of Pg, P. intermedia, P. nigrescens, F. nucleatum, Cr, S. intermedius, C. ochracea and P. melaninogenica (per SD, aHR=1.46; 95% CI, 1.09-1.96, P=0.017). In both the 55+ and 65+ age groups, the Orange-Red cluster (Pm, Pi, Pn, Pg) was associated with increased AD mortality risk. PD and phase 2 (1991-1994) measured Pg were consistently and directly associated with incident AD among older individuals. Interpretation: Evidence for an association between periodontal pathogens and AD and dementia-related outcomes was stronger for older adults. This study presents information that may inform periodontists who treat older adults and calls for a line of inquiry between practitioners focused on Pd and neurodegenerative processes. Funding Statement: This study was entirely supported by the National Institute on Aging, Intramural Research Program (NIA/NIH/IRP). Declaration of Interests: All authors declare no conflict of interest. Ethics Approval Statement: The present study was approved for ethical treatment of participants by the Institutional Review Board of the National Institute on Aging, Intramural Research Program.

Association of alprazolam with major cardiovascular events in patients with hypertension

Anxiety is a mediator for emotional reactivity and acute blood pressure elevations, which are associated with an increased risk of cardiovascular death. Alprazolam is a common medication for anxiolysis. We hypothesized that alprazolam usage can reduce the risk of major adverse cardiovascular events (MACEs) in patients with hypertension. A retrospective cohort study was performed using datasets from Taiwanese Health and Welfare Data. Patients with hypertension were divided into exposed (Alprazolam-exposed) and control groups (non-Alprazolam-exposed) with 1:1 propensity score matching. The study endpoint was the occurrence of MACE. Adjusted hazard ratio (aHR) of MACE risk was estimated using the multiple Cox proportional hazard model. Age-stratified analysis was performed to evaluate the interaction of age and alprazolam use with MACEs. The study cohort consisted of 335 517 alprazolam-exposed patients and 1:1 PSM controls. The mean age was 63.62 ± 12.71 years in the Alprazolam-exposed population. Alprazolam exposure was significantly associated with reduced risk of MACEs (aHR = 0.965, 95% CI = 0.954-0.977), including ischemic stroke (aHR = 0.958, 95% CI = 0.940-0.976), hemorrhagic stroke (aHR = 0.856, 95% CI = 0.821-0.892), myocardial infarction (aHR = 0.933, 95% CI = 0.900-0.968), sudden cardiac death (aHR = 0.955, 95% CI = 0.916-0.996), and all-cause mortality (aHR = 0.921, 95% CI = 0.909-0.932). In the age-subgroup analysis, alprazolam showed the greatest risk reduction effect in hemorrhagic stroke for patients aged <65 years (aHR = 0.779, 95% CI = 0.727-0.835). Alprazolam usage in patients with hypertension was associated with a slightly reduced risk of MACEs and all-cause mortality, and up to 22% reduced risk of hemorrhagic stroke was observed in alprazolam users aged <65 years.

Survival rate of patients with gastric cancer in Hormozgan Province, Iran.

Background: Gastric cancer is the fourth most common form of cancer and the second most common cause of death in the world. It is also one of the most common cancers leading to mortality in Iran. Therefore, this study aimed to determine the survival rate of patients with gastric cancer and its affecting factors in the south of Iran (Hormozgan province). Methods: In this study, all patients with gastric cancer (119 patients) that were diagnosed and registered during 2008 to 2013 in Hormozgan province, were studied. All patients were followed to the end of 2015. Kaplan-Meier method and Cox proportional hazards model were used to draw survival curves and to determine the effective factors on the survival rate of surveyed patients. Moreover, Log-rank test was used to evaluate whether or not survival curves for different groups are statistically equivalent (p<0.05). Results: The mean age of the study population was 58.9±14.91, and most of them were men (72.3% (86 persons)). After diagnosis, the survival rates for 1, 2, 3, 4, and 5 years were 62.2%, 49.4%, 43.7%, 39.7%, and 38% respectively. Survival in men were lower than women, but according to log-rank test this difference was not statistically significant (p=0.325). Also patients with advanced stage cancer had significantly lower survival in comparison to individuals with early stage disease (p<0.001). Based on multiple Cox proportional hazards model, job status of the patients and stage of cancer were effective factors on patients’ survival. Conclusion: Based on the findings of the present study, the survival rate was decreased over time after diagnosis. Stage of a cancer at the time of diagnosis is the most important factor affecting the survival of surveyed patients. This shows that there is a crucial need to diagnos the gastric cancer in early stages.

Severe Upper Limb Injuries in U.S. Military Personnel: Incidence, Risk Factor and Outcomes.

Severe upper limb injuries (SULI) may pose a significant public health challenge for the military; however, SULI has not been previously defined or studied in the US military. Objective: Determine SULI incidence, risk factors, and outcomes. Active Component (AC) U.S. military personnel who served during January 1, 2003 to December 31, 2012 who met the case definition for SULI (N = 213,745) and a random sample from the same population without SULI were included. Data from the Defense Medical Surveillance System and Defense Medical Epidemiology Database was used to calculate incidence. Multiple logistic regression and Cox proportional hazards models were used to analyze SULI risk factors and attrition. SULI incidence was 15/1,000 person-years. Higher SULI risk was observed in men (OR 1.25; 95% CI 1.22-1.27), age 25-29 (OR 1.07; 95% CI 1.05-1.09) compared to age 20-24, E5-E9 (OR 1.14; 95% CI 1.12-1.17) compared to E1-E4, serving in Coast guard (OR 1.62; 95% CI 1.56-1.68) and Air Force (OR 1.17; 95% CI 1.14-1.19) relative to Army and with a deployment history (OR 2.16, 95% CI 2.12-2.19) while SULI risk was lower for blacks (OR 0.91; 95% CI 0.90-0.93) and those in the "other race" category (HR 0.81; 95% CI 0.80-0.84) compared to whites. SULI was associated with 23% increased risk of attrition (HR 1.23; 95% CI 1.22-1.24). The study findings provide preliminary evidence on the incidence, natural history and distribution of SULI in this population. The findings indicate SULI may impact readiness and result in premature military separation.

Elevated Serum Non-HDL (High-Density Lipoprotein) Cholesterol and Triglyceride Levels as Residual Risks for Myocardial Infarction Recurrence Under Statin Treatment.

Objective- Secondary prevention for recurrent myocardial infarction (MI) is one of the most important therapeutic goals in patients with old MI (OMI). Although statins are widely used for this purpose, there remains considerable residual risk even after LDL (low-density lipoprotein cholesterol) is well controlled by statins. Approach and Results- We examined clinical impacts of nHDL (nonhigh-density lipoprotein cholesterol) and its major components triglyceride and LDL as residual risks for acute MI recurrence, using the database of our CHART (Chronic Heart Failure Analysis and Registry in the Tohoku District)-2 Study, the largest-scale cohort study of cardiovascular patients in Japan. We enrolled 1843 consecutive old MI patients treated with statins (mean age 67.3 years, male 19.2%) in the CHART-2 Study. The incidence of recurrent acute MI during the median 8.6-year follow-up was compared among the groups divided by the levels of nHDL (<100, 100-129, and ≥130 mg/dL), LDL (<70, 70-99, and ≥100 mg/dL), triglyceride (<84, 84-149, and ≥150 mg/dL), and combination of LDL and triglyceride. Kaplan-Meier curves and multiple Cox proportional hazards models showed that higher levels of nHDL, but not LDL or triglyceride alone, were associated with higher incidence of recurrent acute MI. Furthermore, higher triglyceride levels were associated with higher incidence of recurrent MI in patients with LDL <100 mg/dL but not in those with LDL ≥100 mg/dL. Conclusions- These results indicate that management of residual risks for acute MI recurrence should include nHDL management considering both LDL and triglyceride in old MI patients under statin treatment. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00418041.

Overview of multivariate regression model analysis and application

Analyses of the multivariate regression model are ued very widely in the medical research. Analytical methods of the mutivariate regression model including multiple linear regression, logistic regression, Poisson regression and Cox proportional hazard model were introduced in this article. The contents of the article covered the application conditions of regression models, analytical procedures, strategies of selecting independent variables, extended discussions of regression models and application notes. It is expected that authors could understand the principle of the mutivariate regression model, accurately use these analytical methods in their research, improve the efficiency of data utilization, and enhance the level of statistical analyses.

The correlation between the incidence of adverse events and progression-free survival in patients treated with cabozantinib for metastatic renal cell carcinoma (mRCC)

Clinical practice shows significant differences in treatment outcomes across patients treated with cabozantinib for metastatic renal cell carcinoma (mRCC). It is not known whether cabozantinib-induced adverse events are predictive factors of survival as in case of drugs such as sunitinib or axitinib. The study participants were 30 adult patients with mRCC treated with cabozantinib as a second- or further line setting. All adverse events were evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Progression-free survival (PFS) values were calculated by taking the beginning of cabozantinib treatment as the start date and either disease progression or death as the end date. PFS were estimated using the Kaplan-Meier method, and compared using the log-rank test. We identified independent PFS predictors using multiple Cox proportional hazards models and reported hazard ratios (HR) with 95% confidence intervals. The median observation time cabozantinib treatment was 7.5months, with a range of 2-15months. During that time, 11 (37%) of the patients had mRCC progression. Median PFS on cabozantinib was not reached, and lower quartile was 6months. All patients developed at least one adverse event in the course of cabozantinib therapy. Hypertension, hypothyroidism and HFS were observed most frequently, in about two-thirds of the patients. The co-incidence of multiple adverse events was common. Hypertension, hypothyroidism, diarrhea and liver toxicity were significantly associated with longer PFS values. Patients with three or more side effects had significantly longer PFS than those with two or fewer. Even though this study was conducted in a small patient sample and the observation time was relatively short our results confirm the predictive value of the incidence of adverse events during cabozantinib treatment in mRCC patients. To the best of our knowledge, this is the first study of this kind conducted in this group of patients.

R0 vs R1 resection in pancreatic cancer: is there a genuine prognostic importance?

Background: Many R0 pancreatic cancer (PDAC) resections are revealed to be R1 resection upon exact histological examination. Thus, the true prognostic importance of R0 vs. R1 resection for survival in PDAC is yet to be uncovered. Methods: Medical databases were screened for prognostic publications that reported adjusted hazard ratios (HR). Furthermore, our prospective institutional database was retrospectively screened for curative PDAC resections according to inclusion criteria (n=254 patients) between 07/2007 and 10/2014. Results: In the meta-analysis, R0 was associated with an improved overall survival [HR 1.45 (95%-CI 1.37-1.52)] and disease free survival [HR 1.44 (1.30-1.59)] in PDAC when compared to R1. Importantly, this effect was present only for pancreatic head resections, both in the meta-analysis [CRM≤1mm: HR 1.21 (1.05-1.39) vs. CRM≥1mm: HR 1.66 (1.46-1.89] and in our cohort (R0≤1mm: 28.8 vs. 14.5 months, p<0.0001; R0≥1mm, 41.2 vs. 16.8 months; p<0.0001). Moreover R1-resections were associated with advanced tumor disease, as indicated by larger tumor size, lymph node metastases, and extended resections. Multiple Cox proportional hazard model revealed G3, pN1, tumor size and R1 (0mm/1mm) as independent predictors of overall survival. Conclusion: R-Status is not a valid prognostic marker in publications before 2010 due to inhomogeneity of cohorts and of histopathological examination. Upon standardized pathological examination, R-status’ prognostic validity is confined only to pancreatic head resections.

Depth of invasion as a predictor of nodal disease and survival in patients with oral tongue squamous cell carcinoma.

Depth of invasion (DOI) in oral cavity cancer is important in determining prognosis. This study aims to determine optimal cut-points of DOI for detection of occult disease and survival. A retrospective cohort study was completed of previously untreated early stage lateral oral tongue cancer. DOI cut-points were computed. Multiple logistic regression and multivariate Cox proportional hazards models were used to assess predictors of occult nodal disease and overall survival (OS) and disease-specific survival (DSS). Occult nodal disease was found in 55 (26%) of the 212 patients. DOI of 7.25 mm was most predictive for occult nodal disease and 8 mm for OS and DSS. DOI was an independent predictor of OS and DSS. The optimal DOI cut-point for detection of occult nodal metastasis was 7.25 and 8 mm for OS and DSS at 5 years. DOI is an independent predictor of OS and DSS.

Factors Affecting the Survival of Therapy Related AML/MDS, Secondary AML and De Novo AML

Introduction:Patients exposed to cytotoxic agents are at a higher risk of developing therapy related AML and MDS (tAML/tMDS), and have poor survival as compared to de novo AML due to high risk of adverse features. Secondary AML (sAML)includes patients with progression from myeloproliferative neoplasms (MPN) and myelodysplastic syndrome (MDS) to AML, considering this progression could be natural history of disease process. Patients with tAML are considered to have an inferior outcome compared with de novo AML. In this retrospective chart review study, we aimed to look at factors affecting the survival of tAML/tMDS, sAML and de novo AML.Method:This retrospective analysis included 219 AML patients treated at Wake Forest Baptist Medical Center between January 2010 and December 2016. Kaplan-Meier estimation was used to evaluate survival at one and two-year period in these three types of AML. Multiple Cox proportional hazards models were used to examine the interaction between baseline characteristics (Table 1) and AML type (tAML/tMDS, sAML, de novo AML) on survival. Backward selection method was used to identify important predictors for a final model. Hazard ratios and 95% CI of all-cause mortality were based on the final Cox model.Results:We analyzed 219 patients with AML diagnosis. Of those 151 (69%) were de novo AML, 25 (11%) sAML and 43 (20%) tAML/tMDS, with mean age of 60.7, 70.7, and 69.7 years respectively. 88% of sAML and 72% of tAML/tMDS were ≥ 65 years compared to 50% of de novo AML patients (p=0.0009). More patients were in underweight/normal BMI (< 24.9) category of sAML (50%) compared to 36% of de novo AML and 21% of tAML/tMDS although this was not statistically significant (p=0.10). There were more females with tAML/tMDS (51%) compared to de novo AML (48%) and sAML (40%) (p=0.52). Most patients in all three groups of AML were white with 79% of de novo AML, 88% of sAML and 88% of tAML/tMDS.Almost one-third of sAML (33%) and tAML/tMDS (38%) were in adverse risk category group with 24% of de novo AML in this category. Most of de novo (62%), sAML (67%) and tAML/tMDS (45%) were in intermediate risk category. There were 5 patients with tAML/tMDS in favorable risk category with zero sAML and 18 de novo AML in this category. 54% of our patients had ECOG performance score of 0-1. A majority of sAML (63%) had a positive smoking history compared to 47% of de novo AML and 44% of tAML/tMDS. Majority of patients in the three categories denied any alcohol use. Incidence of FLT-3 mutation was 23% in de novo AML, 0% in sAML and 9% in tAML/tMDS (p=0.0001). NPM1 mutation was present in 19% of de novo AML, none of sAML and 5% in tAML/tMDS (p = 0.0016). CEBPa mutation was present in 6% of de novo AML, 4% of sAML and 2% of tAML/tMDS.Median survival was 18.5 months for de novo AML (95% CI 14.9- 23.7), 7.2 months for tAML/tMDS (95% CI 3.3- 11.5) and 7.0 months for sAML (95% CI 3.4-15.6). The median survival was longer among males, compared to females with de novo AML (23.2 months in males; 95% CI 18.3-37.1 vs. 14.6 months in females; 95% CI 10.3-19.0) compared to sAML (13.5 months in males; 95% CI 3.8-55 vs, 3.3 months in females; 95% CI 0.2-8.1) and tAML/tMDS (6.3 months in males; 95% CI 4.5-17.8 vs. 7.2 months in females; 95% CI 2.3-11.5) p=0.06. Patients with adverse risk category had a shorter median survival compared to those with favorable risk category, especially in tAML/tMDS but this was not significant.After adjusting for age, risk category and FLT-3 status, the type of AML was not a significant predictor of survival. However, when compared with de novo AML, patients with sAML and tAML/tMDS appear to have a somewhat increased risk of death (HR 1.3; 95% CI 0.7-2.4 and 1.6; 95% CI 0.9, 2.7 respectively). Mortality was 4.5 (95% CI 1.8, 11.3) and 9.3 (95% CI 3.6, 24.0) times higher in patients with intermediate and adverse risk category respectively, when compared to the favorable risk group. Patients with positive FLT-3 had 1.6 times mortality compared to negative FLT-3 (95% CI 1.0, 2.7).Conclusion:We found that median survival was better in de novo AML compared to sAML and tAML/tMDS. There was no difference in survival between sAML and tAML/tMDS. Advancing age increases the odds of death across three types of AML. It is important to note that the effect of patient characteristics on survival is mostly consistent across the AML types and that once the major survival predictors are accounted for, the type of AML is no longer significant. DisclosuresPardee:Amgen: Speakers Bureau; Karyopharm: Research Funding; Novartis: Speakers Bureau; Celgene: Speakers Bureau; Rafael Pharmaceuticals: Employment. Powell:Rafael Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

Smoking cessation sharply reduced lung cancer mortality in a historical cohort of 3185 Chinese silicotic workers from 1981 to 2014

BackgroundPopulation-based studies showed an over 50% decrease in lung cancer risk after quitting smoking for 5–6 years, but the beneficial effect in silicotics remains unknown. We aimed to rectify this knowledge gap using a large historical cohort of 3185 Chinese silicotics since 1981 and followed-up till 2014.MethodsBaseline information on workers’ socio-demographics, smoking habits, occupational history, and medical history was collected. Smoking status was reassessed during follow-up. Multiple Cox proportional hazards model was performed to evaluate the impact of smoking cessation on lung cancer mortality.ResultsOverall, 1942 deaths occurred and 188 lung cancer deaths were identified. Compared with never quitters, silicotics who were new quitters had almost halved their lung cancer risk [hazard ratio (HR) = 0.51, 95%CI: 0.34–0.76], while persistent quitters had a 53% risk reduction (HR = 0.47, 95%CI: 0.33–0.66). Lung cancer mortality approximately halved after quitting smoking for 10 years. While the risk kept decreasing with years since cessation, it did not reverse back to that of never smokers. Persistent quitters with small opacities tended to have higher beneficial effects than those with large opacities.ConclusionsSmoking cessation for 10 years halved lung cancer mortality among silicotics, while the beneficial effect was prominent for patients with small opacities.

The effect of facility volume on treatment guideline compliance and overall survival in oral tongue squamous cell carcinoma.

17 Background: National treatment guidelines guide cancer care using the best available evidence and understanding the drivers of guideline compliance is essential to identifying modifiable factors to improve quality of care. This study aims to explore the impact of facility volume on the rate of guideline compliance in patients with oral tongue cancer and its effect on overall survival. Methods: Using National Cancer Database from 2004 to 2013, this retrospective cohort study investigated patients undergoing curative surgical treatment for oral tongue squamous cell carcinoma. Patients were divided into three tertiles according to mean annual case volume at their treatment facility. Guideline compliance was based on the National Comprehensive Cancer Network oral cavity cancer guidelines. Predictors of guideline compliance and overall survival were determined using multiple logistic regression and Cox Proportional Hazards models. Results: Guideline compliant care was delivered in 54.5% of the 35,810 eligible patients. Those treated at intermediate volume facilities had 1.75 times greater odds of receipt of guideline compliant care (95% CI = 1.57-1.96) and 2.14 times greater in high volume facilities (95% CI = 1.91-2.40) compared to low volume facilities. Guideline compliance (adjusted hazard ratio [HRadj] = 0.78, 95% CI = 0.72-0.84) and treatment at a high volume facility (HRadj= 0.88, 95% CI = 0.80-0.98) were independent predictors of overall survival. Conclusions: Facility volume independently predicted guideline compliance in oral tongue cancer. Guideline compliance and treatment at a high case volume facility were predictors of overall survival. Clinicians should apply guideline compliant care regardless of practice setting and treatment at higher volume centers should be considered.

P1.11-14 Radiological Pleura-Tumor Proximity in Pure-Solid Clinical Stage I Lung Cancer: Its Influence on Lymph Node Metastasis and Recurrence

Lymph node metastasis of lung cancer is an important factor for deciding on surgical indications. Radiological pure-solid lung cancer is a highly aggressive feature, even in small lesions, and it is generally difficult to evaluate lymph node metastasis based on preoperative clinical examinations. We focused on the radiological association between the tumor and pleura and assessed the influence of pleura-tumor proximity on the risk of lymph node metastasis and postoperative recurrence. We retrospectively reviewed a consecutive series of 133 patients with clinical stage I lung cancer possessing pure-solid nodule on chest computed tomography who had undergone lobectomy with systematic lymph node dissection between January 2009 and December 2016. Figure shows the definition of positive pleura-tumor proximity. A multiple logistic regression analysis was used to identify the predictors for lymph node metastasis, and a multiple Cox proportional hazards model was used to identify the predictors for postoperative recurrence, with covariates of age, gender, performance status, resected side, pulmonary function, tumor size, pleural tag, pleura-tumor proximity, and maximum standardized uptake on positron emission tomography. There were 89 men (mean age 70.7 ± 9.6 years). The mean tumor size was 22.9 ± 8.7 mm. Lymph node metastasis was found in 21 patients (15.7%), and postoperative recurrence was found in 24 patients (18%). According to the multivariate analysis, the age (p = 0.013) and positive pleura-tumor proximity (p = 0.036) were the independent predictive factors of lymph node metastasis, and the positive pleura-tumor proximity (p = 0.035) was an independent predictive factor of postoperative recurrence. Pleura-tumor proximity in radiological pure-solid lung cancer was associated with lymph node metastasis and postoperative recurrence. Such pleura-tumor proximity should therefore be taken into consideration in the therapeutic decision-making for stage I lung cancer possessing pure-solid nodules.

The severity of neural invasion decreases overall survival and time until tumor recurrence in patients with pancreatic ductal adenocarcinoma

Introduction: Neural invasion/Pn is recognized as an unfavorable factor decreasing overall survival/OS in patients with pancreatic ductal adenocarcinoma/PDAC. Recently, we could clearly show that Pn is an omnipresent, histopathological feature of PDAC reaching up to nearly 100% of all tumor specimens and that Pn decreases OS and disease-free surviva/DFSl. Yet, the impact of severity of Pn on OS and DFS has not been systematically evaluated. Methods: Therefore, 225 PDAC specimens of patients resected between 07/2007 and 10/2014 were systematically revaluated and our Neural Invasion Severity Score”/NI-SSc was assessed. Afterwards, NI-SSc was correlated with clinical follow-up data focusing on OS and time to tumor recurrence. Results: Overall incidence of Pn was 96%. Strikingly, a high NI-SSc was not even associated with a diminished OS in PDAC patients (median survival: 17.2 months vs. 27.6 months, p = 0.001) but also a strongly decreased DSF (27.7 months vs. 10.5 months, p < 0.001). Moreover, time to local recurrence/LR (10.5 months vs. 27.7 months, p=0.001) and time to distant metastases/DM (12.9 months vs. 27.2 months, p = 0.01) was unfavorably affected by a high NI-SSc in PDAC. Accordingly, NI-SSc was the strongest independent predictor for OS (HR = 1.02; p = 0.01), for LR (HR = 1.05; p < 0.0001) and for DM (HR = 1.01; p = 0.04) by the Multiple Cox proportional hazard model. Conclusion: In PDAC, the severity of Pn is an unfavorable predictor of a crucially shortened OS and time to LR and DM. Therefore, the NI-SSc should gain increased consideration in the planning of individual postoperative treatment for patients with PDAC.

Modern contraceptive use among women of reproductive age in Ghana: analysis of the 2003\u20132014 Ghana Demographic and Health Surveys

BackgroundContraceptives are used in family planning to space or limit pregnancies and are categorized into modern and traditional methods. The modern methods have been proven to be more scientifically effective at preventing unwanted pregnancies than the traditional methods. With data from three (3)-different Demographic and Health Surveys, the aim of this study is to assess the trends and identify factors that consistently influence modern contraceptives’ use among women of the reproductive age group in Ghana.MethodsThe study used secondary data from the 2003, 2008, and 2014 Ghana Demographic Health Surveys (GDHS). The trends of determinants of modern contraceptives use among women of reproductive age in Ghana were determined. A bivariate approach was used to select significant predictors. The Cox proportional hazards model analysis was employed via a multilevel modelling approach.ResultsOut of the total respondents of 2229, 2356, and 4469, 18.75%, 15.75% and 21.53% were modern contraceptives users for 2003, 2008 and 2014 respectively. The multiple cox proportional hazards model analysis identified place of residence and the educational level of a woman as strong predictors of modern contraceptives use in Ghana. Modern contraceptive use is increasing among rural residence. Women who are in formal occupations (professional, clerical, services) are more likely to use modern contraceptives than their colleagues in less formal occupations (manual, agricultural, sales).ConclusionThis study highlights the trends of determinants on modern contraceptive use in Ghana from 2003 to 2014. The most persistent determinants of modern contraceptive use in Ghana during this time period are place of residence and a woman’s educational level. Women working in Agriculture and Sales are the least users of modern contraceptives in Ghana over the period.

Antiplatelet Therapy is Associated with Stent Patency After Iliocaval Venous Stenting.

To examine the effectiveness of antithrombotic medications to prevent venous stent malfunction for iliocaval occlusive disease. A retrospective analysis was performed on 62 patients who underwent technically successful endovascular iliocaval stent placement between May 2008 and April 2017. Clinical records were reviewed for demographic information, procedure details, post-stenting antithrombotic prophylaxis and stent patency on follow-up. Stent malfunction was defined as > 50% stenosis or occlusion at follow-up. Risk factors for stent malfunction were assessed with univariable and multiple Cox proportional hazard models. The median follow-up period was 11.6months (range 0.1-76.4). Overall primary and secondary cumulative patency rates at 12months were 70.0% and 92.4%, respectively. After stent placement, 97% of patients received anticoagulation with warfarin, enoxaparin or a factor Xa inhibitor. In addition, 61% received antiplatelet prophylaxis with aspirin, clopidogrel or a combination. In multiple Cox regression analysis, post-stenting antiplatelet use remained significantly associated with primary stent patency (HR = 0.28, P = 0.022). After iliocaval venous stenting, stent patency was best predicted by concomitant antiplatelet and anticoagulation therapy rather than anticoagulation alone. This novel finding warrants further research underlying mechanisms leading to venous stent thrombosis, and has implications for optimal medical management after venous stenting.

A comparison of the operative outcomes of D1 and D2 gastrectomy performed at a single Western center with multiple surgeons: a retrospective analysis with propensity score matching

BackgroundThere has been worldwide debate on lymphadenectomy for gastric cancer, with increasing consensus on performing an extended (D2) resection. There is a paucity of data in Australia. Our aim is to compare overall outcomes between a D1 and D2 lymphadenectomy for gastric cancer in a single specialist unit.MethodsWe performed a retrospective analysis on patients who underwent a curative primary gastric resection for gastric adenocarcinoma between January 1996 and April 2016, primary outcomes included overall survival (OS) and disease-free survival (DFS). Propensity score matching (PSM) analysis was used to balance covariates between D1/D1+ and D2 groups. Kaplan-Meier survival curves of D1/D1+ versus D2 were constructed and evaluated using the log-rank test with subgroup analyses for pathological node (pN) status. Multiple Cox proportional hazards model was used to determine predictors of overall survival.ResultsTwo hundred four patients underwent a gastrectomy, 54 had D1/D1+, and 150 had a D2 lymphadenectomy. After PSM, there were 39 patients in each group, the 10-year OS for D1/D1+ was 52.1 and 76.2% for D2 (p = 0.008), and 10-year DFS was 35% for D1 and 58.1% for D2 (p = 0.058). Subgroup analysis showed that node-negative (N0) patients had improved 5-year OS for D2 (90.9%), compared to D1/D1+ (76.4%) (p = 0.028). There was no difference in operative mortality between the groups (D1 vs D2: 2 vs 0%, p = 0.314), nor in post-operative complications (p = 0.227). Multiple Cox analysis showed advanced tumor stage (stages III and IV), and lymphadenectomy type (D1) and the presence of postoperative complications were independent predictors of poor overall survival.ConclusionsD2 lymphadenectomy with spleen and pancreas preservation can be performed safely on patients with gastric adenocarcinoma. Significant improvement in overall survival is observed in patients with N0 disease who underwent D2 lymphadenectomy without increasing operative morbidity or mortality. This paper supports the notion of a global consensus for a D2 lymphadenectomy, particularly in the Western context.

Dipeptidyl peptidase-4 inhibitor use is associated with decreased risk of fracture in patients with type 2 diabetes: a population-based cohort study.

The aim of this study was to investigate the putative link between dipeptidyl peptidase-4 inhibitor (DPP-4i) use and the risk of fracture in patients with type 2 diabetes. This propensity-score-matched population-based cohort study was performed between 2009 and 2013 on patients with type 2 diabetes who were stable metformin users. A total of 3996 patients with type 2 diabetes used DPP-4i as a second-line antidiabetic drug. The same number of matched non-DPP-4i users were followed up until fracture occurrence, health insurance policy termination, or the end of 2013. The incidence rates of overall and cause-specific fractures were estimated based on the Poisson assumption. A multiple Cox proportional hazard model was used to estimate the covariate-adjusted hazard ratio (HR) and 95% confidence interval (CI) to determine the association between DPP-4i use and overall and cause-specific fractures stratified by age and sex. Over a maximum follow-up period of 5 years, 340 DPP-4i users and 419 non-DPP-4i users were newly diagnosed with fractures, yielding incidence rates of 28.03 and 32.04 per 1000 people per year, respectively. The Cox proportional hazard model revealed that DPP-4i use significantly reduced the risk of all-cause fractures and upper extremity fractures, with adjusted HRs of 0.86 (95% CI: 0.74-0.99) and 0.75 (95% CI: 0.59-0.95), respectively. The aforementioned associations of DDP-4i use with fracture were sustained across sex and age stratifications. The results of this study supported the premise that DPP-4i usage is associated with a reduced risk of all-cause fractures and upper extremity fractures in patients with type 2 diabetes.