Risk-adjusted Cox Regression Analysis Research Articles

Does Side Really Matter? Survival Analysis among Patients with Right- Versus Left-Sided Colon Cancer: A Propensity Score-Adjusted Analysis.

Right- and left-sided colon cancer are increasingly regarded as two independent disease entities based on different gene expression profiles as well as underlying genetic mutations. Data regarding prognosis and survival are heterogeneous and more favorable in cases of left-sided colon cancer. The purpose of this study was to evaluate the long-term oncological outcome for patients with left-sided versus right-sided stage I-III colon cancer. Overall, 318 consecutive patients who underwent surgery for right- or left-sided sided colon cancer between 2001 and 2014 were analyzed. Analysis was performed applying a prospectively maintained database with respect to overall, disease-specific, and relative survival, using Cox regression and propensity score analyses. A total of 155 patients (48.7%) presented with right-sided colon cancer and 163 patients (51.3%) presented with left-sided colon cancer. In risk-adjusted Cox regression analysis, tumor location had no significant impact on overall survival (hazard ratio [HR] 1.53, 95% confidence interval [CI] 0.80-2.92; p = 0.197), disease-specific survival (HR 1.36, 95% CI 0.76-2.44; p = 0.301), and relative survival (HR 1.70, 95% CI 0.89-3.27; p = 0.107). After propensity score matching, the results from risk-adjusted Cox regression analysis were confirmed. Stratified by American Joint Committee on Cancer stage, patients with right-sided stage II colon cancer had a statistically significant superior relative survival compared with patents with left-sided colon cancer. No significant negative impact on overall, disease-specific, or relative survival could be observed in patients with right- versus left-sided colon cancer after risk adjustment, using multivariable Cox regression and propensity score analyses.

Negative impact of hyperglycaemia on tocilizumab therapy in Covid-19 patients

Tocilizumab (TCZ) is used for treating moderate-to-severe Covid-19 pneumonia by targeting interleukin-6 receptors (IL-6Rs) and reducing cytokine release. Yet, in spite of this therapy, patients with vs. patients without diabetes have an adverse disease course. In fact, glucose homoeostasis has influenced the outcomes of diabetes patients with infectious diseases. Of the 475 Covid-19-positive patients admitted to infectious disease departments (University of Bologna, University Vanvitelli of Napoli, San Sebastiano Caserta Hospital) in Italy since 1 March 2020, 31 (39.7%) hyperglycaemic and 47 (60.3%) normoglycaemic patients (blood glucose levels ≥140mg/dL) were retrospectively evaluated at admission and during their hospital stay. Of note, 20 (64%) hyperglycaemic and 11 (23.4%) normoglycaemic patients had diabetes (P<0.01). At admission, hyperglycaemic vs. normoglycaemic patients had fivefold higher IL-6 levels, which persisted even after TCZ administration (P<0.05). Intriguingly, in a risk-adjusted Cox regression analysis, TCZ in hyperglycaemic patients failed to attenuate risk of severe outcomes as it did in normoglycaemic patients (P<0.009). Also, in hyperglycaemic patients, higher IL-6 plasma levels reduced the effects of TCZ, while adding IL-6 levels to the Cox regression model led to loss of significance (P<0.07) of its effects. Moreover, there was evidence that optimal Covid-19 infection management with TCZ is not achieved during hyperglycaemia in both diabetic and non-diabetic patients. These data may be of interest to currently ongoing clinical trials of TCZ effects in Covid-19 patients and of optimal control of glycaemia in this patient subset.

Outcomes in Patients With Hyperglycemia Affected by COVID-19: Can We Do More on Glycemic Control?

OBJECTIVEAn important prognostic factor in any form of infection seems to be glucose control in patients with type 2 diabetes. There is no information about the effects of tight glycemic control on coronavirus disease 2019 (COVID-19) outcomes in patients with hyperglycemia. Therefore, we examined the effects of optimal glycemic control in patients with hyperglycemia affected by COVID-19.RESEARCH DESIGN AND METHODSFifty-nine patients with COVID-19 hospitalized with moderate disease were evaluated. On the basis of admission glycemia >7.77 mmol/L, patients were divided into hyperglycemic and normoglycemic groups. Interleukin 6 (IL-6) and D-dimer levels were evaluated at admission and weekly during hospitalization. The composite end point was severe disease, admission to an intensive care unit, use of mechanical ventilation, or death.RESULTSThirty-four (57.6%) patients were normoglycemic and 25 (42.4%) were hyperglycemic. In the hyperglycemic group, 7 (28%) and 18 (72%) patients were diagnosed with diabetes already before admission, and 10 (40%) and 15 (60%) were treated without and with insulin infusion, respectively. The mean of glycemia during hospitalization was 10.65 ± 0.84 mmol/L in the no insulin infusion group and 7.69 ± 1.85 mmol/L in the insulin infusion group. At baseline, IL-6 and D-dimer levels were significantly higher in the hyperglycemic group than in the normoglycemic group (P < 0.001). Even though all patients were on standard treatment for COVID-19 infection, IL-6 and D-dimer levels persisted higher in patients with hyperglycemia during hospitalization. In a risk-adjusted Cox regression analysis, both patients with hyperglycemia and patients with diabetes had a higher risk of severe disease than those without diabetes and with normoglycemia. Cox regression analysis evidenced that patients with hyperglycemia treated with insulin infusion had a lower risk of severe disease than patients without insulin infusion.CONCLUSIONSInsulin infusion may be an effective method for achieving glycemic targets and improving outcomes in patients with COVID-19.

Type II diabetes mellitus and the incidence of amyotrophic lateral sclerosis.

The aim of this study was to investigate the relationship between type II diabetes mellitus (T2DM) and ALS incidence using the National Health Insurance Research Database and Serious Disabling Disease database of Taiwan. This was a population-based cohort study. The index date was the date of the first T2DM diagnosis + 365days. We included T2DM patients diagnosis between 2000 and 2013 (n = 2,135,427). These patients were matched by sex, age, urbanization, and insurance premium at a ratio of 1:1 to include patients without diabetes mellitus. Competing risk-adjusted Cox regression analysis was performed to investigate the association between T2DM and the incidence of ALS. In the patients not stratified by age, T2DM was not associated with the incidence of ALS after controlling for confounding factors. The interaction test of age subgroup (< 55 and ≥ 55years) and T2DM on ALS risk was significance (p < 0.001). Subgroup analysis showed that T2DM was negatively associated with ALS in patients whose age at the first T2DM diagnosis was ≥ 55years. Among T2DM patients, T2DM combined with hypertension was negatively associated with ALS among patients whose age at the first T2DM diagnosis was ≥ 55years. Among T2DM patients, T2DM combined with hyperlipidemia was positively associated with ALS among patients whose age at the first T2DM diagnosis was < 55years. The late-onset of T2DM may exert negative association with ALS, especially when combined with hypertension. The early-onset of T2DM may exert positive association with ALS, especially when combined with hyperlipidemia.

Prognostic impact of anastomotic leakage after elective colon resection for cancer – A propensity score matched analysis of 628 patients

BackgroundThere is limited information regarding the impact of anastomotic leakage on oncologic outcome in exclusively colon cancer patients. MethodsThe colorectal database of the Department of Surgery of the University of Heidelberg was used to assess the impact of anastomotic leakage on oncologic outcome in patients undergoing curative resection for Stage I–III colon cancer. Risk-adjusted Cox regression analysis and propensity score methods were used to assess overall, disease-free, and relative survival. Results628 patients of which 26 (4.1%) experienced anastomotic leakage were analysed. Anastomotic leakage was associated with significantly worse overall, disease-free and relative survival in univariate and multivariate analysis. The analysis after exact propensity score matching confirmed the negative impact of anastomotic leakage on overall (HR 2.62, 95% CI 1.33–5.18, p = .011), disease-free (HR 2.28, 95% CI 1.16–4.47, p = .027) and relative survival (HR 3.70, 95% CI 1.82–7.52, p < .001). 5-year overall survival was 51.6% (95% CI 34.5–77.2%) for patients with anastomotic leakage compared to 77.7% (95% CI 73.0–82.8%) for patients without anastomotic leakage. ConclusionsAll conceivable efforts should be made to avoid anastomotic leakage after colon resection for cancer not only to evade short-term consequences but also to allow for adequate long-term outcome.

Asthma, corticosteroid use and schizophrenia: A nationwide population-based study in Taiwan.

ObjectiveAsthma and corticosteroid use have been implicated as possible risk factors for schizophrenia. The retrospective cohort study herein aimed to investigate the association between asthma, corticosteroid use, and schizophrenia.MethodLongitudinal data (2000 to 2007) from adults with asthma (n = 50,046) and without asthma (n = 50,046) were compared on measures of schizophrenia incidence using Taiwan’s National Health Insurance Research Database (NHIRD). Incidence of schizophrenia diagnosis (ICD-9 codes 295.XX) between 2000 and 2007 were compared between groups. Competing risk-adjusted Cox regression analyses were conducted, adjusting for sex, age, residence, socioeconomic status, corticosteroid use, outpatient and emergency room visit frequency, Charlson comorbidity index, and total length of hospital stays days for any disorder.ResultsOf the 75,069 subjects, 238 received a diagnosis of schizophrenia. The mean (SD) follow-up interval for all subjects was 5.8 (2.3) years. After adjusting for potential confounding factors, asthma was associated with significantly greater hazard ratio for incident schizophrenia 1.40 (95% CI = 1.05, 1.87). Additional factors associated with greater incidence of schizophrenia were rural residence, lower economic status, and poor general health. Older age (i.e. ≥65 years) was negatively associated with schizophrenia incidence. Corticosteroid use was not associated with increased risk for schizophrenia.ConclusionsAsthma was associated with increased risk for schizophrenia. The results herein suggest that a convergent disturbance in the immune-inflammatory system may contribute to the pathoetiology of asthma and schizophrenia.

Asthma associated with chronic rhinosinusitis: a population-based study.

Few studies have investigated the relationship between asthma and chronic rhinosinusitis (CRS). The present study investigated the association between asthma and the risk of CRS in a large national sample. Patients newly diagnosed with asthma (International Classification of Diseases, Ninth Revision [ICD-9], Clinical Modification code 493) between 2000 and 2008 were identified from the Taiwan National Health Insurance Research Database. The cases were compared with sex-, age-, residence-, and insurance premium-matched controls, and both groups were followed until the end of 2009 for incidences of CRS with or without nasal polyps (CRSwNP or CRSsNP, respectively). Competing risk-adjusted Cox regression analyses were performed after adjustment for sex, age, residence, insurance premium, steroid use, hyperlipidemia, diabetes, hypertension, coronary artery disease, Charlson comorbidity index score, and mortality. We also performed a case-control study to determine the association between asthma and CRS. The cohort study analysis examined 81,462 patients with a mean ± standard deviation (SD) follow-up period of 5.8 ± 2.4 years. Asthma was an independent predictor of CRSsNP (hazard ratio = 2.58; 95% confidence interval [CI], 2.20 to 3.03; p < 0.001) in the fully adjusted models. In the case-control analysis, both CRSwNP and CRSsNP were associated with asthma in the fully adjusted models. Asthma was associated with increased risks of CRSwNP and CRSsNP, independent of several potential confounding factors.

Chronic obstructive pulmonary disease and anxiety disorders: a nationwide population-based study in Taiwan.

Few studies have investigated the relationship between chronic obstructive pulmonary disease (COPD) and anxiety disorder outcomes. We sought to investigate the association in a large national sample. Cases were identified from Taiwan's National Health Insurance Research Database who were aged 15 years and above, with a new primary diagnosis of COPD (International Classification of Diseases, Ninth Revision codes: 491, 492, 494 and 496) between 2000 and 2007. The 29,951 cases identified were compared to 29,951 controls matched on sex, age, urban/rural residence and socioeconomic status based on insurance premium. Both groups were followed until the end of 2008 for instances of anxiety disorders. Competing risk-adjusted Cox regression analyses were applied, adjusting for matching variables, Charlson comorbidity index, hospital admission days and daily dose of prednisone. Of the 59,902 subjects, 3951 were found to have anxiety disorders during a mean (SD) follow-up period of 5.5 (2.5) years. COPD, female, urban residence, lower dose of prednisone use, depressive disorders and higher outpatient visits were independent predictors of incident anxiety disorder. COPD was associated with increased risk of an anxiety disorder diagnosis, independent of a number of potential confounding factors.

Risk of bipolar disorder in patients with COPD: a population-based cohort study.

Few studies have investigated the relationship between chronic obstructive pulmonary disease (COPD) and bipolar outcomes in the world. We sought to investigate the association between COPD and risk of bipolar disorder in a large national sample. The insured aged 15years or more with a new primary diagnosis of COPD (ICD-9: 491, 492, 494 and 496) between 2000 and 2007 were identified from Taiwan's National Health Insurance Research Database. We included individuals with an inpatient diagnosis of COPD and/or at least 1year of two diagnoses of COPD in outpatient services. These 35,558 cases were compared to 35,558 sex-, age-, residence- and insurance premium-matched controls. We followed both groups until the end of 2008 for incidence of bipolar disorder, defined as ICD-9 codes 296.0-296.16, 296.4-296.81 and 296.89. Competing risk-adjusted Cox regression analyses were applied with adjusting for sex, age, residence, insurance premium, prednisone use, Charlson comorbidity index, diabetes, hypertension, hyperlipidemia, cardiovascular diseases, hospital admission days, outpatients' visits and mortality. Of the total 71,116 subjects, 202 were newly diagnosed with bipolar disorder during the study period. The mean follow-up time was 6.0(SD=2.2)years. COPD, younger age, lower economic status, lower dose of prednisone use, higher hospital admission days and higher outpatient visits were independent predictors of bipolar disorder. COPD was associated with increased risk of bipolar disorder independent of a number of potential confounding factors in this study.

Urgent surgery after emergency presentation for colorectal cancer has no impact on overall and disease-free survival: a propensity score analysis.

BackgroundIt remains a matter of debate whether colorectal cancer resection in an emergency setting negatively impacts on survival. Our objective was therefore to assess the impact of urgent versus elective operation on overall and disease-free survival in patients undergoing resection for colorectal cancer by using propensity score adjusted analysis.MethodsIn a single-center study patients operated for colorectal cancer between 1989 and 2013 were identified from a prospectively maintained database. Median follow-up was 44 months. Patients with neoadjuvant treatment were excluded. The impact of urgent operation on overall and disease-free survival was assessed using both Cox regression and propensity score analyses.ResultsOf 747 patients with colorectal cancer, 84 (11 %) had urgent and 663 elective cancer resection. The propensity score revealed strongly biased patient characteristics (0.22 ± 0.16 vs. 0.10 ± 0.09; P < 0.001). In unadjusted analysis urgent operation was associated with a 35 % increased risk of overall mortality (hazard ratio(HR) of death = 1.35, 95 % confidence interval(CI):1.02–1.78, P = 0.045). In risk-adjusted Cox regression analysis urgent operation was not associated with poor overall (HR = 1.08, 95 %CI:0.79–1.48; P = 0.629) or disease-free survival (HR = 1.02, 95 %CI:0.76–1.38; P = 0.877). Similarly in propensity score analysis urgent operation did not influence overall (HR = 0.98, 95 % CI:0.74–1.29), P = 0.872) and disease-free survival (HR = 0.89, 95 %CI:0.68 to 1.16, P = 0.387).ConclusionsThis study provides evidence that worse oncologic outcomes after urgent operation for colorectal cancer are caused by clinical circumstances and not due to the urgent operation itself. Urgent operation is not a risk factor for colorectal cancer resection.

Prognostic Relevance of Mucinous Subtype in a Population-based Propensity Score Analysis of 40,083 Rectal Cancer Patients.

The prognostic relevance of mucinous histology in colorectal cancer remains unclear, especially for rectal neoplasms. The objective of this study was to evaluate if mucinous subtype has a relevant impact on overall survival (OS) and cancer-specific survival (CSS) of patients with adenocarcinomas of the rectum. On the basis of the data set of the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute of the United States, patients with rectal cancer between 2004 and 2011 were identified. Risk-adjusted Cox regression analysis and propensity score methods were used to assess OS and CSS. In total, 40,083 patients with stage I-IV rectal cancer, of whom 2483 (6.2%) had mucinous histology, were included in this study. In unadjusted analysis, the 5-year OS and CSS for patients with a mucinous adenocarcinoma was 54.3% [95% confidence interval (CI) 52.0-56.7] and 61.4% (95% CI 59.1-63.9) compared to 66.4% (95% CI 65.8-67.0) and 74.5% (95% CI 73.9-75.1) for patients with nonmucinous adenocarcinoma (P<0.001). The survival disadvantage persisting in risk-adjusted Cox proportional hazard regression analysis [hazard ratio (HR) 1.23, 95% CI 1.15-1.31, P<0.001 and 1.25, 95% CI 1.16-1.35, P<0.001) disappeared after propensity score matching (OS: HR=0.96, 95% CI 0.76-1.21, P=0.722; CSS: HR 1.06, 95% CI 0.80-1.40, P=0.693). This population-based, propensity score matched analysis shows that mucinous histology itself does not constrain survival in rectal cancer patients. Therefore, treatment decisions should not be different according to mucinous histology.

Association of asthma and anxiety: A nationwide population-based study in Taiwan

BackgroundFew studies have investigated the bidirectional relationship between asthma and anxiety; we sought to investigate asthma and anxiety in a large national sample. MethodsCases were identified from Taiwan's National Health Insurance Research Database with a new primary diagnosis of asthma (ICD-9:493) aged more than 15 years between 2000 and 2007. Case status required the presence of any inpatient diagnosis of asthma and/or at least one year diagnosis of asthma in outpatient service. These 22,797 cases were compared to 22,797 sex-, age-, residence- and insurance premium-matched controls and both groups were followed until the end of 2008 for instances of anxiety, defined as ICD-9 codes 300.0, 300.01, 300.02, 300.2, 300.21, 300.23, 300.3. Competing risk adjusted Cox regression analyses were applied, adjusting for sex, age, residence, insurance premium, prednisone use, Charlson comorbidity index, cardiovascular disease, diabetes, depression disorder, and hospital admission days for any disorder. The effect of asthma on the risk of panic disorder and the effect of anxiety disorder on the risk of later asthma were also examined as competing risk adjusted Cox regression analyses ResultsOf the 45,594 subjects, 2792 were ascertained as having anxiety during a mean (SD) follow-up period of 5.3 (2.5) years. Asthma, females, older age, rural residence, depression disorder, and prednisone use were independent risks on anxiety in the fully adjusted model. Anxiety, older age, rural residence, and prednisone use were independent risks on asthma in the fully adjusted model. LimitationsThe severity of asthma and anxiety disorder, the duration of prednisone treatment and adherence, stressful life events, smoking, family history and relationship were not evaluated. ConclusionsBidirectional relationship between asthma and anxiety disorder was confirmed in this population, in dependent of a number of potential confounding factors.

Chronic obstructive pulmonary disease predicts chronic rhinosinusitis without nasal polyps: A population-based study.

Few studies have investigated the relationship between chronic obstructive pulmonary disease (COPD) and chronic rhinosinusitis without nasal polyps (CRSsNP) outcomes. The aim of this study was to investigate the association between COPD and the risk of CRSsNP in a large national sample. Patients 15 years or older with a new primary diagnosis of COPD (International Classification of Diseases, Ninth edition [ICD-9], 491, 492, 494, and 496) between 2000 and 2007 were identified from the National Health Insurance Research Database of Taiwan. The patients were compared with sex-, age-, residence-, and insurance premium-matched controls, and both groups were followed up until the end of 2008 for instances of CRSsNP, defined as ICD-9 codes CRS (473, 473.0, 473.1, 473.2, 473.3, 473.8, and 473.9), excluding NP (471, 471.0, 471.1, 471.8, and 471.9). Competing risk-adjusted Cox regression analyses were applied after adjusting for sex, age, residence, insurance premium, steroid use (topical or systemic), hyperlipidemia, diabetes, hypertension, coronary artery disease, hospital admission days, and mortality. We included 34,029 cases and 34,029 matched controls in this study. Among the 68,058 subjects, 569 developed CRSsNP during a mean (standard deviation [SD]) follow-up period of 5.0 years (SD 2.2 years). COPD was an independent predictor of CRSsNP in the fully adjusted model (hazard ratio = 3.24; 95% CI = 2.65-3.96; p < 0.01). COPD was associated with an increased risk of CRSsNP in this study population, independent of a number of potential confounding factors.

Asthma and self-harm: A population-based cohort study in Taiwan

ObjectiveFew studies have investigated the relationship between asthma and suicidality-related outcomes in the world. We sought to investigate the association between asthma and risk of non-fatal self-harm in a large national sample. MethodsCases aged 10years and over were identified from Taiwan's National Health Insurance Research Database with a new primary diagnosis of asthma (ICD-9:493) between 2000 and 2008. Case status required the presence of any inpatient diagnosis of asthma and/or at least two recorded diagnoses and 1year duration of asthma in outpatient services. These 27,781 cases were compared to 138,905 sex- and age-matched controls and both groups were followed until end of 2008 for instances of self-harm, defined as ICD-9 codes E950-E959 (self-harm causes) and E980-E989 (undetermined causes). Competing risk adjusted Cox regression analyses were applied, adjusting for sex, age, residence (urban/rural), insurance premium, episode of psychiatric disease, montelukast, Charlson comorbidity index and mortality. ResultsOf the 166,686 subjects, 445 carried out self-harm during a mean (SD) follow-up period of 5.84 (2.35) years. Asthma (hazard ratio=1.70, 95% CI: 1.35–2.14), age, residence, episode of psychiatric disease and Charlson comorbidity index were independent risks on self-harm in the fully adjusted model. ConclusionsAsthma was associated with increased risk of self-harm in this population, independent of a number of potential confounding factors including montelukast use. This reinforces the need to consider mental health in routine asthma care, and to consider asthma as a potentially important stressor in people with comorbid mental disorder.

Association of asthma and bipolar disorder: A nationwide population-based study in Taiwan

BackgroundThe relationship between asthma and bipolar disorder has received little research. We sought to investigate this in a large national sample. Previous studies have found mood changes after prednisone use in asthma patients, and we therefore also investigated this exposure in relation to bipolar disorder. MethodsCases were identified from Taiwan׳s National Health Insurance Research Database with a new primary diagnosis of asthma (ICD-9:493) between 2000 and 2007. Case status required the presence of any inpatient diagnosis of asthma and/or at least one year diagnosis of asthma in outpatient service. These 46,558 cases were compared to 46,558 sex-, age-, residence- and insurance premium-matched controls and both groups were followed until the end of 2008 for first diagnosis of bipolar disorder (ICD-9 codes 296.0 to 296.16, 296.4 to 296.81 and 296.89). Competing risk adjusted Cox regression analyses were applied, adjusting for sex, age, residence, insurance premium, prednisone, hyperthyroidism, COPD (chronic obstructive pulmonary disease), Charlson comorbidity index, and hospital admission days for any disorder. ResultsOf the 93,116 subjects, 161 were ascertained as having bipolar disorder during a mean (SD) follow-up period of 5.7 (2.2) years. Asthma was an independent risk for bipolar disorder in the fully adjusted model. Higher daily dose of prednisone was a risk factor in asthma cases. LimitationsThe severity of asthma and bipolar disorder, and the route/duration of prednisone treatment were not evaluated. ConclusionsAsthma was associated with increased risk of bipolar disorder. Higher daily dose of prednisone was associated with a further increased risk.