scholarly journals Long-term risk of a major cardiovascular event by apoB, apoA-1, and the apoB/apoA-1 ratio—Experience from the Swedish AMORIS cohort: A cohort study

PLoS Medicine ◽  
2021 ◽  
Vol 18 (12) ◽  
pp. e1003853
Author(s):  
Göran Walldius ◽  
Ulf de Faire ◽  
Lars Alfredsson ◽  
Karin Leander ◽  
Peter Westerholm ◽  
...  
Keyword(s):  
Cohort Study ◽  
Cox Regression ◽  
Early Recognition ◽  
Age Groups ◽  
Major Adverse Cardiovascular Events ◽  
Men And Women ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Nested Case Control ◽  
The Impact

Background Elevated apolipoprotein B (apoB) and elevated apoB/apoA-1 ratio increase the risk of myocardial infarction (MI) and stroke, whereas high apoA-1 is protective. We study how these apolipoproteins are associated with major adverse cardiovascular events (MACEs), whether apoA-1 contributes to this association, and whether abnormal values occur decades before such events develop. Methods and findings In the Swedish AMORIS (Apolipoprotein-related MOrtality RISk) cohort study, 137,100 men and women aged 25–84 years were followed an average 17.8 years. ApoB, apoA-1, and the apoB/apoA-1 ratio were analysed in relation to MACEs (non-fatal MI, stroke, and cardiovascular [CV] mortality), yielding 22,473 events. Hazard ratios (HRs) were estimated using Cox regression. Kaplan–Meier estimates were used to investigate the relationship of MACEs with increasing quintiles of the apoB/apoA-1 ratio in all age groups for both sexes. In nested case–control analyses, cases were randomly matched to age- and sex-matched controls, yielding population trajectories for apolipoproteins. Increased level of apoB and increased apoB/apoA-1 ratio were associated with risk of MACE and all clinical sub-components in both men and women across all ages (10th versus first decile in both sexes combined: HR 1.7 for MACE and 2.7 for non-fatal MI). Decreased values of apoA-1 potentiated the impact of apoB at all levels of apoB (on average across apoB range: 40% increase in HR for MACE and 72% increase in HR for non-fatal MI), indicating that the apoB/apoA-1 ratio covers a broader range of persons with dyslipidaemia at risk than apoB alone. In both men and women, MACEs occurred earlier on average for each increasing quintile of the apoB/apoA-1 ratio. Individuals with the highest levels of apoB/apoA-1 ratio experienced CV events on average several years earlier than those with lower ratios. Higher apoB/apoA-1 ratio in cases of MACE versus controls was seen already about 20 years before the event. A limitation of this study was that adjustment for tobacco smoking and hypertension was only possible in a small validation study. Conclusions An imbalance between apoB and apoA-1 resulting in an increased apoB/apoA-1 ratio is strongly associated with the outcome MACE and its sub-components, in both men and women of all ages. An increased apoB/apoA-1 ratio already 2 decades before events calls for early recognition and primary prevention. Simple evidence-based cut values should be considered in future cardiovascular guidelines.

scholarly journals Survival analysis of time to SARS-CoV-2 PCR negativisation to optimise PCR prescription in health workers: the Henares COVID-19 healthcare workers cohort study

2021 ◽  
pp. oemed-2020-106903
Author(s):  
Julio González Martin-Moro ◽  
Marta Chamorro Gómez ◽  
Galicia Dávila Fernández ◽  
Ana Elices Apellaniz ◽  
Ana Fernández Hortelano ◽  
...  
Keyword(s):  
Cohort Study ◽  
Healthcare Workers ◽  
Cox Regression ◽  
Health Workers ◽  
Upper Respiratory Tract ◽  
Rt Pcr ◽  
Kaplan Meier ◽  
Confounding Variables ◽  
The Impact ◽  
Associated Variables

ObjectivesReverse transcriptase PCR (RT-PCR) is considered the gold standard in diagnosing COVID-19. Infected healthcare workers do not go back to work until RT-PCR has demonstrated that the virus is no longer present in the upper respiratory tract. The aim of this study is to determine the most efficient time to perform RT-PCR prior to healthcare workers’ reincorporation.Materials and methodsThis is a cohort study of healthcare workers with RT-PCR-confirmed COVID-19. Data were collected using the medical charts of healthcare workers and completed with a telephone interview. Kaplan-Meier curves were used to determine the influence of several variables on the time to RT-PCR negativisation. The impact of the variables on survival was assessed using the Breslow test. A Cox regression model was developed including the associated variables.Results159 subjects with a positive RT-PCR out of 374 workers with suspected COVID-19 were included. The median time to negativisation was 25 days from symptom onset (IQR 20–35 days). Presence of IgG, dyspnoea, cough and throat pain were associated with significant longer time to negativisation. Cox logistic regression was used to adjust for confounding variables. Only dyspnoea and cough remained in the model as significant determinants of prolonged negativisation time. Adjusted HRs were 0.68 (0.48–096) for dyspnoea and 0.61 (0.42–0.88) for dry cough.ConclusionsRT-PCR during the first 3 weeks leads to a high percentage of positive results. In the presence of respiratory symptoms, negativisation took nearly 1 week more. Those who developed antibodies needed longer time to negativisate.

H3K27M-mutant Diffuse Midline Gliomas should be Further Molecularly Stratified: An Integrated Analysis of 669 Patients

2021 ◽  
Author(s):  
Huy Gia Vuong ◽  
Hieu Trong Le ◽  
Tam N.M. Ngo ◽  
Kar-Ming Fung ◽  
James D. Battiste ◽  
...  
Keyword(s):  
Cox Regression ◽  
Fatal Outcome ◽  
Extent Of Resection ◽  
Tumor Location ◽  
Genetic Alterations ◽  
Integrated Analysis ◽  
Prognostic Impact ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
The Impact

Abstract Introduction: H3K27M-mutated diffuse midline gliomas (H3-DMGs) are aggressive tumors with a fatal outcome. This study integrating individual patient data (IPD) from published studies aimed to investigate the prognostic impact of different genetic alterations on survival of these patients.Methods: We accessed PubMed and Web of Science to search for relevant articles. Studies were included if they have available data of follow-up and additional molecular investigation of H3-DMGs. For survival analysis, Kaplan-Meier analysis and Cox regression models were utilized, and corresponding hazard ratios (HR) and 95% confidence intervals (CI) were computed to analyze the impact of genetic events on overall survival (OS).Result: We included 30 studies with 669 H3-DMGs. TP53 mutations were the most common second alteration among these neoplasms. In univariate Cox regression model, TP53 mutation was an indicator of shortened survival (HR = 1.446; 95% CI = 1.143-1.829) whereas ACVR1 (HR = 0.712; 95% CI = 0.518-0.976) and FGFR1 mutations (HR = 0.408; 95% CI = 0.208-0.799) conferred prolonged survival. In addition, ATRX loss was also associated with a better OS (HR = 0.620; 95% CI = 0.386-0.996). Adjusted for age, gender, tumor location, and the extent of resection, the presence of TP53 mutations, the absence of ACVR1 or FGFR1 mutations remained significantly poor prognostic factors.Conclusions: We outlined the prognostic importance of additional genetic alterations in H3-DMGs and recommended that these neoplasms should be further molecularly segregated. It could help neuro-oncologists better evaluate the risk stratification of patients and consider pertinent treatments.

scholarly journals Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases: a multinational cohort study

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Heinz Freisling ◽  
Vivian Viallon ◽  
Hannah Lennon ◽  
Vincenzo Bagnardi ◽  
Cristian Ricci ◽  
...  
Keyword(s):  
Cohort Study ◽  
Cox Regression ◽  
Healthy Lifestyle ◽  
Smoking Status ◽  
Lifestyle Factors ◽  
Healthy Lifestyles ◽  
Men And Women ◽  
Cardiometabolic Diseases ◽  
Hazard Ratios ◽  
Risk Of Cancer

Abstract Background Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases. Methods In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs. Results During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and women with healthy lifestyles. Conclusion Pre-diagnostic healthy lifestyle behaviours were strongly inversely associated with the risk of cancer and cardiometabolic diseases, and with the prognosis of these diseases by reducing risk of multimorbidity.

scholarly journals Sex-Specific Clinical Characteristics and Long-Term Outcomes in Patients With Myocardial Infarction With Non-obstructive Coronary Arteries

2021 ◽  
Vol 8 ◽  
Author(s):  
Side Gao ◽  
Wenjian Ma ◽  
Sizhuang Huang ◽  
Xuze Lin ◽  
Mengyue Yu
Keyword(s):  
Myocardial Infarction ◽  
Coronary Arteries ◽  
Cox Regression ◽  
Older Age ◽  
Major Adverse Cardiovascular Events ◽  
Future Research ◽  
Long Term Outcomes ◽  
Men And Women ◽  
Kaplan Meier

Background: Sex differences in clinical profiles and prognosis after acute myocardial infarction have been addressed for decades. However, the sex-based disparities among patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) remain largely unreported. Here, we investigated sex-specific characteristics and long-term outcomes in MINOCA population.Methods: A total of 1,179 MINOCA patients were enrolled, including 867 men and 312 women. The mean follow-up was 41.7 months. The primary endpoint was a composite of major adverse cardiovascular events (MACE), including all-cause death, non-fatal reinfarction, revascularization, non-fatal stroke, and hospitalization for unstable angina or heart failure. Baseline data and outcomes were compared. Kaplan-Meier curves and Cox regression analyses were used to identify association between sex and prognosis.Results: Female patients with MINOCA had more risk profiles with regard to older age and higher prevalence of hypertension and diabetes compared with men. The evidence-based medical treatment was similar in men and women. The incidence of MACE (men vs. women: 13.8 vs. 15.3%, p = 0.504) did not differ significantly between the sexes. The Kaplan-Meier analysis also indicated that women had a similar incidence of MACE compared to men (log rank p = 0.385). After multivariate adjustment, female sex was not associated with the risk of MACE in overall (adjusted hazard ratio 1.02, 95% confidence interval: 0.72–1.44, p = 0.916) and in subgroups of MINOCA patients.Conclusion: The long-term outcomes were similar for men and women presenting with MINOCA despite older age and more comorbidities in women. Future research should aim to improve in-hospital and post-discharge care for both sexes with MINOCA.

scholarly journals Irradiation of the Subventricular Zone and Subgranular Zone in High- and Low-Grade Glioma Patients: an Atlas-based Analysis on Overall Survival

2022 ◽  
Author(s):  
Danique E Bruil ◽  
Szabolcs David ◽  
Steven H J Nagtegaal ◽  
Sophia F A M de Sonnaville ◽  
Joost J C Verhoeff
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Low Grade ◽  
Subgranular Zone ◽  
Mr Images ◽  
Repair Capacity ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Reduce Tumor Growth ◽  
The Impact

Abstract Background Neural stem cells in the subventricular- (SVZ) and subgranular zone (SGZ) are hypothesized to support growth of glioma. Therefore, irradiation of the SVZ and SGZ might reduce tumor growth and might improve overall survival (OS). However, it may also inhibit the repair capacity of brain tissue. The aim of this retrospective cohort study is to assess the impact of SVZ and SGZ radiotherapy doses on OS of patients with high-grade (HGG) or low-grade (LGG) glioma. Methods We included 273 glioma patients who received radiotherapy. We created an SVZ atlas, shared openly with this work, while SGZ labels were taken from the CoBRA atlas. Next, SVZ and SGZ regions were automatically delineated on T1 MR-images. Dose and OS correlations were investigated with Cox regression and Kaplan-Meier analysis. Results Cox regression analyses showed significant hazard ratios for SVZ dose (univariate: 1.029/Gy, p<0.001; multivariate: 1.103/Gy, p = 0.002) and SGZ dose (univariate: 1.023/Gy, p<0.001; multivariate: 1.055/Gy, p<0.001) in HGG patients. Kaplan-Meier analysis showed significant correlations between OS and high/low dose groups for HGG patients (SVZ: respectively 10.7 months (>30.33 Gy) vs 14.0 months (<30.33 Gy) median OS, p = 0.011; SGZ: respectively 10.7 months (>29.11 Gy) vs 15.5 months (<29.11 Gy) median OS, p<0.001). No correlations between dose and OS were found for LGG patients. Conclusion Irradiation doses on neurogenic areas correlate negatively with OS in patients with HGG. Whether sparing of the SVZ and SGZ during radiotherapy improves OS, should be subject of prospective studies.

scholarly journals Irradiation of the Subventricular Zone and Subgranular Zone: an Atlas-based analysis on Overall Survival in High- and Low-grade Glioma Patients

2021 ◽  
Author(s):  
Danique Bruil ◽  
Szabolcs David ◽  
Steven Nagtegaal ◽  
Sophia de Sonnaville ◽  
Joost Verhoeff
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Low Grade ◽  
Subgranular Zone ◽  
Mr Images ◽  
Repair Capacity ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Reduce Tumor Growth ◽  
The Impact

Background: Neural stem cells in the subventricular- (SVZ) and subgranular zone (SGZ) are hypothesized to support growth of glioma. Therefore, irradiation of the SVZ and SGZ might reduce tumor growth and might improve overall survival (OS). However, it may also inhibit the repair capacity of brain tissue. The aim of this retrospective cohort study is to assess the impact of SVZ and SGZ radiotherapy doses on OS of patients with high-grade (HGG) or low-grade (LGG) glioma. Methods: We included 273 glioma patients who received radiotherapy. We created an SVZ atlas, shared openly with this work, while SGZ labels were taken from the CoBRA atlas. Next, SVZ and SGZ regions were automatically delineated on T1 MR-images. Dose and OS correlations were investigated with Cox regression and Kaplan-Meier analysis. Results: Cox regression analyses showed significant hazard ratios for SVZ dose (univariate: 1.029/Gy, p<0.001; multivariate: 1.103/Gy, p = 0.002) and SGZ dose (univariate: 1.023/Gy, p<0.001; multivariate: 1.055/Gy, p<0.001) in HGG patients. Kaplan-Meier analysis showed significant correlations between OS and high/low dose groups for HGG patients (SVZ: respectively 10.7 months (>30.33 Gy) vs 14.0 months (<30.33 Gy) median OS, p = 0.011; SGZ: respectively 10.7 months (>29.11 Gy) vs 15.5 months (<29.11 Gy) median OS, p<0.001). No correlations between dose and OS were not found for LGG patients. Conclusion: Irradiation doses on neurogenic areas correlate negatively with OS in patients with HGG. Whether sparing of the SVZ and SGZ during radiotherapy improves OS, should be subject of prospective studies.

scholarly journals Impact of prediabetes on long-term cardiovascular outcomes in patients with myocardial infarction with nonobstructive coronary arteries

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Side Gao ◽  
Wenjian Ma ◽  
Sizhuang Huang ◽  
Xuze Lin ◽  
Mengyue Yu
Keyword(s):  
Myocardial Infarction ◽  
Coronary Arteries ◽  
Cox Regression ◽  
Early Recognition ◽  
Past History ◽  
Major Adverse Cardiovascular Events ◽  
Abnormal Glucose Metabolism ◽  
Kaplan Meier ◽  
Increased Risk

Abstract Background Abnormal glucose metabolism including diabetes (DM) and prediabetes (pre-DM) have been reported as predictors of poorer outcomes after acute myocardial infarction (AMI). However, the prognostic value of pre-DM in patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) remains unclear. Methods A total of 1179 MINOCA patients were prospectively recruited and divided into normoglycemia (NG), pre-DM, and DM groups according to glycated hemoglobin (HbA1c) levels or past history. The primary endpoint was a composite of major adverse cardiovascular events (MACE), including all-cause death, nonfatal MI, nonfatal stroke, revascularization and hospitalization for unstable angina or heart failure. Kaplan–Meier and Cox regression analyses were performed. Results Patients with pre-DM and DM had a significantly higher incidence of MACE compared with NG group (10.8%, 16.1%, 19.4%; p = 0.003) over the median follow-up of 41.7 months. After multivariate adjustment, both pre-DM and DM were significantly associated with an increased risk of MACE (NG as reference; pre-DM: 1.45, 95% CI 1.03–2.09, p = 0.042; DM: HR 1.79, 95% CI 1.20–2.66, p = 0.005). At subgroup analysis, pre-DM remained a robust risk factor of MACE compared to NG. In addition, pre-DM had a similar impact as DM on long-term prognosis in patients with MINOCA. Conclusions Pre-DM defined as raised HbA1c was associated with a poor prognosis in patients with MINOCA. Routine assessment of HbA1c enables an early recognition of pre-DM and thus may facilitate risk stratification in this specific population.

Feasibility of reusing time-matched controls in an overlapping cohort

2016 ◽  
Vol 27 (6) ◽  
pp. 1818-1829 ◽  
Author(s):  
Bénédicte Delcoigne ◽  
Niels Hagenbuch ◽  
Maria EC Schelin ◽  
Agus Salim ◽  
Linda S Lindström ◽  
...  
Keyword(s):  
Cox Regression ◽  
Secondary Analysis ◽  
Sampling Bias ◽  
Case Control ◽  
Control Data ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Multifocal Tumor ◽  
Nested Case Control ◽  
Study Base

The methods developed for secondary analysis of nested case-control data have been illustrated only in simplified settings in a common cohort and have not found their way into biostatistical practice. This paper demonstrates the feasibility of reusing prior nested case-control data in a realistic setting where a new outcome is available in an overlapping cohort where no new controls were gathered and where all data have been anonymised. Using basic information about the background cohort and sampling criteria, the new cases and prior data are “aligned” to identify the common underlying study base. With this study base, a Kaplan–Meier table of the prior outcome extracts the risk sets required to calculate the weights to assign to the controls to remove the sampling bias. A weighted Cox regression, implemented in standard statistical software, provides unbiased hazard ratios. Using the method to compare cases of contralateral breast cancer to available controls from a prior study of metastases, we identified a multifocal tumor as a risk factor that has not been reported previously. We examine the sensitivity of the method to an imperfect weighting scheme and discuss its merits and pitfalls to provide guidance for its use in medical research studies.

scholarly journals Serum ANCA and Overall Mortality: A 10-Year Retrospective Cohort Study on 1,024 Italian Subjects

2021 ◽  
Vol 12 ◽  
Author(s):  
Enrico Brunetta ◽  
Giacomo Ramponi ◽  
Marco Folci ◽  
Maria De Santis ◽  
Emanuela Morenghi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cohort Study ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Cox Regression ◽  
Antineutrophil Cytoplasmic Antibodies ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Perinuclear Anca ◽  
Worse Prognosis

BackgroundAntineutrophil cytoplasmic antibodies (ANCA) are primarily involved in the pathogenesis of ANCA-associated vasculitides (AAV). However, ANCA may also be present in healthy subjects and in patients with autoimmune disorders different from AAV. We hypothesized that serum ANCA are associated with a worse prognosis in disorders other than AAV.ObjectiveWe investigated the association between the overall survival and the presence of serum ANCA in 1,024 Italian subjects with various testing indications in a 10-year interval.MethodsIn this retrospective cohort study, a population of 6,285 patients (many of whom were subsequently excluded due to our criteria) who tested for ANCA at a single center in 10 years was considered, and life status and comorbidities of subjects were collected. We compared the overall survival of ANCA-positive and ANCA-negative patients by means of Kaplan-Meier curves, while a multivariable adjusted Cox regression was used to evaluate the association between the ANCA status and the outcome (death) in terms of hazard ratios (HR) with 95% confidence intervals (CI).ResultsThe positivity of perinuclear ANCA (pANCA) increased significantly mortality (HR, 1.60; 95% CI, 1.10–2.32), while cytoplasmic ANCA (cANCA) positivity failed to show a significant association (HR, 1.43; 95% CI, 0.77–2.68). The increased mortality rate was observed for both pANCA and cANCA in patients suffering from rheumatic disorders. No association was found between mortality and anti-MPO (HR, 0.63; 95% CI, 0.20–2.00) or anti-PR3 (HR, 0.98; 95% CI, 0.24–3.96) after adjusting for confounders.ConclusionsSerum pANCA and cANCA are independent negative prognostic factors in patients with concurrent autoimmune diseases.

The Efficacy of Etoposide-Based Therapy in Adult Secondary Hemophagocytic Lymphohistiocytosis

2021 ◽  
pp. 1-9
Author(s):  
Leonard Naymagon ◽  
Douglas Tremblay ◽  
John Mascarenhas
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Proportional Hazards ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Significant Difference ◽  
The Impact

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank <i>p</i> = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633–1.799, <i>p</i> = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.

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