Body height in young adult men and risk of dementia later in adult life

This study examined the relationship between body height and dementia and explored the impact of intelligence level, educational attainment, early life environment and familial factors. A total of 666,333 men, 70,608 brothers, and 7388 twin brothers born 1939–1959 and examined at the conscript board were followed in Danish nationwide registers (1969–2016). Cox regression models were applied to analyze the association between body height and dementia. Within-brothers and within-twin pair analyses were conducted to explore the role of shared familial factors including partly shared genetics. In total, 10,599 men were diagnosed with dementia. The association between one z-score difference in body height and dementia (HR: 0.90, 95% CI: 0.89;0.90) was inverse and weakened slightly after adjustment for intelligence test scores and educational level. The associations persisted in within-brother analysis and revealed a stronger, but less precise, point estimate than the cohort analysis of brothers. The twin analysis showed similar, but imprecise estimates.

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Body height in young adult men and risk of dementia later in adult life

10.1101/748467 ◽

2019 ◽

Author(s):

Terese Sara Høj Jørgensen ◽

Gunhild Tidemann Christensen ◽

Kaare Christensen ◽

Thorkild IA Sørensen ◽

Merete Osler

Keyword(s):

Cox Regression ◽

Body Height ◽

Adult Life ◽

Familial Factors ◽

Adult Men ◽

Early Life Environment ◽

Intelligence Test Scores ◽

The Impact ◽

The Relationship

ABSTRACTThis study examined the relationship between body height and dementia and explored the impact of intelligence level, educational attainment, early life environment and familial factors. A total of 666,333 men, 70,608 brothers, and 7,388 twin brothers born 1939-1959 and examined at the conscript board were followed in Danish nationwide registers (1969-2016). Cox regression models were applied to analyze the association between body height and dementia. Within-brothers and within-twin pair analyses were conducted to explore the role of shared familial factors including partly shared genetics. In total, 10,599 men were diagnosed with dementia. The association between one z-score difference in body height and dementia (HR: 0.90, 95%CI: 0.89;0.90) was inverse and weakened slightly after adjustment for intelligence test scores and educational level. The within-brother analyses revealed a smaller estimate for dementia diagnosis the cohort analyses of brothers. The twin analysis showed similar, though less clear associations, which were not statistically significant.

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Cardiovascular Risk After Sepsis: Understanding the Role of Statin Indications and the Impact of Clinical Inertia on Prescribing Patterns

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248420933395 ◽

2020 ◽

Vol 25 (6) ◽

pp. 541-547

Author(s):

Vedant A. Gupta ◽

Talal S. Alnabelsi ◽

Sandipan Shringi ◽

Steve W. Leung ◽

Vincent L. Sorrell

Keyword(s):

Cohort Analysis ◽

Prescribing Patterns ◽

Clinical Inertia ◽

Major Adverse Cardiovascular Events ◽

Prescribing Practices ◽

Retrospective Cohort Analysis ◽

The Mean ◽

The Impact ◽

Statin Use

Introduction: Patients with sepsis have high rates of major adverse cardiovascular events (MACE) in the literature, but the stratification of those at risk has been limited. Statin indicated groups provides clear criteria for therapy, but the risk of MACE after sepsis based on these groups has never been assessed. Materials and Methods: This was a retrospective cohort analysis conducted on adult patients admitted from January 1, 2013, to December 31, 2013, with suspected or confirmed sepsis and data available on statin use. Patients’ past medical history; statin use prior, during, or at time of discharge; and occurrence of MACE were recorded from electronic health records. Result: A total of 321 patients were screened and 265 were found to have data available on statin use. The mean age of the patients was 59 ± 15 years and 47% were female. Overall, 9% were observed to have a MACE at 1 year, with significantly higher rates in those in a statin indicated group (12.2%). On admission, 174 patients were not taking a statin out of whom 52% were in a statin indicated group. Among those in a statin indicated group who survived to hospital discharge, only 10% not on a statin on admission received a statin on discharge, whereas 89% on a statin on admission received a statin on discharge. Conclusion: There is a high risk of MACE after sepsis especially among those in statin indicated groups with significant clinical inertia in prescribing practices.

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The Impact of Rituximab and Radiotherapy On Treatment Outcome of Patients with DLBCL and Skeletal Involvement

Blood ◽

10.1182/blood.v120.21.690.690 ◽

2012 ◽

Vol 120 (21) ◽

pp. 690-690

Author(s):

Gerhard Held ◽

Samira Zeynalova ◽

Niels Murawski ◽

Marita Ziepert ◽

Barbara Kempf ◽

...

Keyword(s):

Overall Survival ◽

Board Of Directors ◽

Cox Regression ◽

Multivariable Analysis ◽

Event Free Survival ◽

Advisory Committees ◽

Free Survival ◽

Skeletal Involvement ◽

The Impact

Abstract Abstract 690 Background: There is limited information on the role of skeletal involvement in DLBCL patients treated with rituximab. Methods: In a retrospective subgroup analysis patients with aggressive B-cell lymphomas with and without skeletal involvement were compared with respect to clinical presentation, event-free and overall survival. Results: Of 3840 patients 292 (7.6%) had skeletal involvement. In a multivariable analysis of patients treated within the randomized MInT and RICOVER-60 trials, the two largest randomized trials addressing the role of rituximab in DLBCL to date, skeletal involvement was associated with a reduced hazard ratio (HR) of 0.8 (p=0.181) for event-free survival and 0.7 (p=0.083) for overall survival for patients treated without, but with an increased HR (1.5; p=0.048) for event-free and (1.1; p=0.828) for overall survival in patients treated with rituximab. This was due to the failure of rituximab to improve the outcome of patients with skeletal involvement. In the MInT trial, the 3-year EFS rates were 64% without and 63% with rituximab (p=0.680) and the 3-year OS rates were 83% without and 90% with rituximab (p=0.542). similarly, in the RICOVER-60 trial, the 3-year EFS rates were 45% without and 50% with rituximab (p=0.593) and the 3-year OS rates were 68% without and 68% with rituximab. In a Cox regression model for event-free survival adjusted for the IPI risk factors a relevant interaction (HR 1.5; p=0.056) term between rituximab and skeletal involvement was observed. In contrast to rituximab, additive radiotherapy to sites of skeletal involvement was associated with a better outcome: 3-year EFS rates were 40% without and 75% with radiotherapy (p<0.001), 3-year OS rates were 70% without and 86% with radiotherapy to sites of skeletal involvement (p=0.064). In a multivariable analysis radiotherapy reduced the risk for an event in EFS by 70% (HR=0.3; p=0.001) and by 50% in OS (HR=0.5; p=0.111). Conclusion: Addition of rituximab failed, but radiotherapy to sites of skeletal involvement did improve the outcome of DLBCL patients with skeletal involvement. Radiotherapy to sites of skeletal involvement, though abandoned by many cooperative groups world-wide, is recommended in the rituximab era, unless prospective trials demonstrate that it might be omitted in cases with a negative PET after immunochemotherapy. Disclosures: Dreyling: Roche: Membership on an entity's Board of Directors or advisory committees. Hallek:Roche: Membership on an entity's Board of Directors or advisory committees. Schmitz:Chugai: Membership on an entity's Board of Directors or advisory committees. Pfreundschuh:Roche: Membership on an entity's Board of Directors or advisory committees; Chugai: Consultancy.

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Integrated Bioinformatics Data Analysis and Experimental Studies Reveals Prognostic Significance of ALDH Family in Endometria Cancer

10.21203/rs.3.rs-427053/v1 ◽

2021 ◽

Author(s):

Zhou-Tong Dai ◽

Yuan Xiang ◽

Xing-Hua Liao

Keyword(s):

Cell Lines ◽

Cox Regression ◽

Prognostic Significance ◽

Experimental Studies ◽

Female Reproductive Tract ◽

The Body ◽

Mouse Tumor ◽

The Impact

Abstract Background Uterine Corpus Endometrial Cancer (UCEC) is one of the three common malignant tumors of the female reproductive tract. According to reports, the cure rate of early UCEC can reach 95%. Therefore, the development of prognostic markers will help UCEC patients to find the disease earlier and develop treatment earlier. The ALDH family was first discovered to be the essential gene of the ethanol metabolism pathway in the body. Recent studies have shown that ALDH can participate in the regulation of cancer. Methods We used the gene profile data of 33 cancers in the TCGA database to analyze the expression and survival of the ALDH family. GO, KEGG, PPI multiple functional analysis was used to predict the regulatory role of ALDH family in cancer. In addition, using CCK-8, colony formation, nude mouse tumor formation and other methods, the in vitro function of UCEC cancer cell lines was tested to further confirm the key role of ALDH2 expression in the proliferation of UCEC cell lines. Finally, Lasso and Cox regression methods were used to establish an overall survival prognosis model based on ALDH2 expression. Result In our research, we explored the expression of ALDH family in 33 cancers. It was found that ALDH2 was abnormally expressed in UCEC. Besides, in vivo and in vitro experiments were conducted to explore the effect of ALDH2 expression on the proliferation of UCEC cell lines. Meanwhile, the change of its expression is not due to gene mutations, but is regulated by miR-135-3p. At the same time, the impact of ALDH2 changes on the survival of UCEC patients is deeply discussed. Finally, a nomogram for predicting survival was constructed, with a C-index of 0.798 and AUC of 0.764. Conclusion This study suggests that ALDH2 may play a crucial role in UCEC progression and has the potential as a prognostic biomarker of UCEC.

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Relationship Between Multimorbidity, Combination and All-Cause Mortality Among Older Adults: A Retrospective Cohort Analysis

10.21203/rs.3.rs-122536/v1 ◽

2020 ◽

Author(s):

Kun He ◽

Wenli Zhang ◽

Xueqi Hu ◽

Hao Zhao ◽

Bingxin Guo ◽

...

Keyword(s):

Older Adults ◽

Mortality Risk ◽

Cox Regression ◽

Cohort Analysis ◽

Relative Effect ◽

Long Term Conditions ◽

Cox Models ◽

Chinese Older Adults ◽

All Cause Mortality ◽

The Impact

Abstract Background: Previous studies have evaluated the association of multimorbidity with higher mortality, but epidemiologic data on the association between the combination of multimorbidity and all-cause mortality risk are rare. We aimed to examine the relationship between multimorbidity (number/combination) and all-cause mortality in Chinese older adults. Methods: We conducted a population-based study of 50,100 Chinese participants. Cox regression models were used to estimate the impact of long-term conditions (LTCs) on all-cause mortality. Results: The prevalence of multimorbidity was 31.35% and all-cause mortality was 8.01% (50,100 participants). In adjusted Cox models, the hazard rations (HRs) and 95% confidence intervals (CIs) of all-cause mortality risk for those with 1, 2, and ≥ 3 LTCs compared with those with no LTCs was 1.10 (1.01-1.20), 1.21 (1.10-1.33), and 1.46 (1.27-1.67), respectively (Ptrend <0.001). In the LTCs ≥ 2 category, the combination of chronic diseases that included hypertension, diabetes, CHD, COPD, and stroke had the greatest impact on mortality. In the stratified model by age and sex, absolute all-cause mortality was higher among the ≥ 75 age group with an increasing number of LTCs. However, the relative effect size of the increasing number of LTCs on higher mortality risk was larger among those < 75 years.Conclusions: The risk of all-cause mortality is increased with the number of multimorbidity among Chinese older adults, particularly combinations.

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Risk factors for outbreaks of COVID-19 in care homes following hospital discharge: a national cohort analysis

10.1101/2020.08.24.20168955 ◽

2020 ◽

Cited By ~ 1

Author(s):

Chris Emmerson ◽

James P Adamson ◽

Drew Turner ◽

Mike B Gravenor ◽

Jane Salmon ◽

...

Keyword(s):

Hospital Discharge ◽

Cox Regression ◽

Care Home ◽

Cohort Analysis ◽

Time Dependent ◽

Care Homes ◽

Health Board ◽

High Morbidity ◽

Discharge From Hospital ◽

The Impact

Abstract Background Adult residential and nursing care homes are settings in which older and often vulnerable people live in close proximity. This population experiences a higher proportion of respiratory and gastrointestinal illnesses than the general population and has been shown to have a high morbidity and mortality in relation to COVID-19. Methods We examined the number of hospital discharges to all Welsh adult care homes and the subsequent outbreaks of COVID-19 occurring over an 18 week period 22 February and 27 June 2020. A Cox proportional hazards regression model was used to assess the impact of time-dependent exposure to hospital discharge on the incidence of the first known outbreak, over a window of 7-21 days after discharge, and adjusted for care home characteristics (including size, type of provision and health board). Results A total of 1068 care homes were monitored; 330 homes experienced an outbreak of COVID-19, and 511 homes received a discharge from hospital over the study period. The exposure to discharge from hospital was not associated with a significant increase in the risk of a new outbreak (hazard ratio 1.15, 95% CI 0.89, 1.49, p = 0.28), after adjusting for care home size, which was by far the most significant predictor. Hazard ratios (95% CI) in comparison to homes of <10 residents were: 3.4 (2.0, 5.8) for 10-24 residents; 8.3 (5.0, 13.8) for 25-49 residents; and 17.3 (9.6, 31.1) for homes of 50+ residents. When stratified for care home size, the outbreak rates were very similar for periods when homes were exposed to a hospital discharge, in comparison to periods when homes were unexposed. Conclusion Our analyses showed that large homes were at considerably greater risk of outbreaks throughout the epidemic, and after adjusting for care home size, a discharge from hospital was not associated with a significant increase in risk. Keywords: COVID-19, care homes, hospital discharge, outbreak, time dependent Cox regression

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Effect of chronic treatment of combined statins and aspirin on the risk of prostate cancer detection.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.5_suppl.185 ◽

2012 ◽

Vol 30 (5_suppl) ◽

pp. 185-185

Author(s):

Cristina Suarez ◽

Rafael Morales ◽

Jose Placer ◽

Isaac Nunez ◽

Jacques Planas ◽

...

Keyword(s):

Prostate Cancer ◽

Multivariate Analysis ◽

Chronic Treatment ◽

Univariate Analysis ◽

Combined Treatment ◽

Adult Men ◽

Cancer Aggressiveness ◽

Increased Risk ◽

The Impact

185 Background: The role of chronic treatment (ChT) with statins and aspirin on prostate cancer (PC) carcinogenesis is controversial. Both drugs are frequently used in adult men who are at risk of PC, and many of them receive both drugs simultaneously. The impact of the combined treatment (CT) with statins and aspirin on PC risk has never been reported. We proposed to explore the influence of ChT with statins and aspirin in the PC risk detection and their aggressiveness. Methods: 2408 men were consecutively biopsied for cause: PSA > 4 ng/mL (64.4%), abnormal DRE (9%) or both (26.6%). ChT with statins and aspirin (>1 year) was controlled. Median age was 68 years (46–86) and median PSA 7.0 ng/mL (0.7-1279). At least 10 cores, plus 1 to 8 additional cores, were obtained. The PC detection rate was 35.2% and the Gleason score was < 7 in 20.8%, 7 in 50.9% and > 7 (HGPC) in 28.3%. Multivariate and univariate analysis were done and OR calculated to analyze the strength of the relationships. Results: 440 men (18.3%) were receiving statins alone (SA), 160 (6.6%) aspirin alone (AA), and 304 (12.6%) both drugs simultaneously. Multivariate analysis showed that CT was the only independent predictor of a reduced risk of PC detection, p=0.025, (OR 0.589, 95%CI 0.370-0-936). PC was detected in 552 of 1502 men (36.7%) not receiving statins or aspirin, 34.5% (152/440) receiving SA, 40% (64/160) receiving AA, and in 26.3% (80/304) receiving statins and aspirin simultaneously. Related to cancer aggressiveness, multivariate analysis showed that combined treatment predicted significantly an increased risk of HGPC, p=0.013, (OR 2.672, 95%CI 1.226-5.825). HGPC was detected in 136 of 552 (24.6%) PCs detected in men not receiving statins or aspirin, in 40 of 152 (26.3%) PCs detected in men receiving SA, in 24 of 64 (37.7%) PCs detected in men receiving AA, and in 40 of 80 (50%) PCs detected in men receiving statins and aspirin simultaneously. Conclusions: This study suggests that ChT with the combination of statins and aspirin reduce significantly the risk of PC detection in men subjected to prostate biopsy for cause. However, this reduction of PC detection is accompanied by a significant increase of PC aggressiveness.

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The impact of routine ESAS use on overall survival: Results of a population-based retrospective matched cohort analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.6509 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 6509-6509 ◽

Cited By ~ 6

Author(s):

Lisa Catherine Barbera ◽

Rinku Sutradhar ◽

Craig Earle ◽

Nicole Mittmann ◽

Hsien Seow ◽

...

Keyword(s):

Overall Survival ◽

Cancer Patients ◽

Cox Regression ◽

Cohort Analysis ◽

Symptom Assessment ◽

Assessment System ◽

Cancer Type ◽

Matched Cohort ◽

Study Objective ◽

The Impact

6509 Background: The study objective was to examine the impact of routine Edmonton Symptom Assessment System (ESAS) use on overall survival among adult cancer patients. We hypothesized that patients exposed to ESAS would have better overall survival rates than those who didn’t have ESAS. Methods: The effect of ESAS screening on survival was evaluated in a retrospective matched cohort study. The cohort included all Ontario patients aged 18 or older who were diagnosed with cancer between 2007 and 2015. Patients completing at least one ESAS assessment during the study were considered exposed. The index date was the day of their first ESAS assessment. Follow up time for each patient was segmented into one of three phases: initial, continuing, or palliative care. Exposed and unexposed patients were matched 1:1 using hard (birth year ± 2 years, cancer diagnosis date ± 1 year, cancer type and sex) and propensity-score matching (14 measures including cancer stage, treatments received, and comorbidity). Matched patients were followed until death or the end of study at Dec 31, 2015. Kaplan-Meier curves and multivariable Cox regression were used to evaluate the impact of ESAS on survival. Results: There were 128,893 pairs well matched on all baseline characteristics (standardized difference < 0.1). The probability of survival within the first 5 years was higher among those exposed to ESAS compared to those who were not (73.8% vs. 72.0%, P-value < 0.0001). In the multivariable Cox regression model, ESAS assessment was significantly associated with a decreased mortality risk (HR: 0.49, 95% CI: 0.48-0.49) and this protective effect was seen across all phases. Conclusions: ESAS exposure is associated with improved survival in cancer patients, in all phases of care. To the extent possible, extensive matching methods have mitigated biases inherent to observational data. This provides real world evidence of the impact of routine symptom assessment in cancer care.

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The impact of weight change during treatment with targeted therapy in patients with metastatic renal cell carcinoma (mRCC).

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.557 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 557-557

Author(s):

Laurence Albiges ◽

Rana R. McKay ◽

Xun Lin ◽

Guillermo de Velasco ◽

Ronit Simantov ◽

...

Keyword(s):

Targeted Therapy ◽

Weight Change ◽

Cox Regression ◽

Progression Free Survival ◽

Baseline Body Mass Index ◽

Free Survival ◽

Management Measures ◽

Kaplan Meier ◽

The Impact

557 Background: A growing body of evidence suggests a relationship between baseline body mass index and outcomes in patients (pts) with mRCC. However, the role of weight loss (WL) during treatment in pts with mRCC is poorly characterized. The aim of this study was to investigate the impact of weight change in mRCC pts treated with targeted agents. Methods: We conducted an analysis of mRCC pts treated on phase II-III clinical trials sponsored by Pfizer from 2003-2013. Weight change was defined as WL (≥ 5% weight reduction from baseline), stable weight (SW) or weight gain (WG, ≥2 % weight increase). We assessed the impact of weight change on overall survival (OS) (primary endpoint), progression-free survival (PFS) and overall response rate (ORR) at week (wk) 12. Statistical analyses were performed using Cox regression and Kaplan-Meier method. Multivariate analysis was adjusted for known prognostic factors for mRCC, including IMDC criteria. Results: Among 3,311 pts, 1,916 (58 %) had SW, 936 (28 %) had WL and 459 (14%) had WG at wk 12. Overall, pts with WL demonstrated both reduced OS and PFS compared to SW (median OS: 18.68 vs. 26.94 vs. 23.03 months in WL, SW and WG respectively; median PFS: 7.17 vs. 10.12 vs. 9.93 months in WL, SW and WG), and were consistent when considering 2 other time points (table). WL at wk 12 was associated with worse ORR (23.4 vs. 32.1 vs. 35.9% in WL, SW, WG; adjusted odd ratio 0.715, 95% CI 0.590-0.867, p=0.03). Discontinuation rate due to adverse events was similar between groups. Conclusions: We demonstrated that WL during therapy for mRCC is strongly associated with worse clinical outcomes. This observation remains valid for WL at 6, 12 and 24 weeks. Weight change may be an early prognostic factor and guide physician in clinical management. Measures to avoid WL during therapy may lead to better outcomes from targeted therapy. [Table: see text]

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miR-361-3p Regulates Liver Tumor-initiating Cells Expansion and Chemo-resistance

10.21203/rs.3.rs-54212/v1 ◽

2020 ◽

Author(s):

Shuping Qu ◽

Xiaobing Zhang ◽

Hengwei Fan ◽

Yue Wu ◽

Jian Zhai ◽

...

Keyword(s):

Liver Tumor ◽

Cohort Analysis ◽

The Self ◽

Tumor Initiating Cells ◽

Self Renewal ◽

Sorafenib Treatment ◽

The Impact

Abstract Background: Increasing evidence shows that liver tumor-initiating cells (T-ICs) closely associated with the progression, metastasis, recurrence and chemo-resistance of hepatocellular carcinoma (HCC). However, the underlying mechanism for the propagation of liver T-ICs remains unclear. The purpose of our study was to explore the role of miR-361-3p in the expansion of liver T-ICs and the potential molecular mechanism.Results: Flow cytometry analysis was performed to isolate CD24+, CD133+ or EpCAM+ cells from primary HCC cells or HCC cell lines. Real-time PCR was used to detect the expression of miR-361-3p in liver T-ICs. The impact of miR-361-3p on liver T-ICS expansion was investigated both in vivo and in vitro. The correlation between miR-361-3p expression and TACE (transcatheter arterial chemoembolization) or sorafenib benefits in HCC was evaluated in patient cohorts. miR-361-3p expression is upregulated in liver T-ICs. Knockdown of miR-361-3p impairs the self-renewal and tumorigenicity liver T-ICs. Conversely, forced miR-361-3p expression enhances the self-renewal and tumorigenicity liver T-ICs. Mechanistically, miR-361-3p directly targets SOX1 via binding its 3’-UTR in liver T-ICs. Moreover, miR-361-3p knockdown hepatoma cells are more sensitive to cisplatin or sorafenib treatment. Clinical cohort analysis demonstrates that miR-361-3p low HCC patients are benefited from TACE or sorafenib treatment. Conclusions: Our findings revealed the crucial role of the miR-361-3p in liver T-IC expansion and TACE or sorafenib response, rendering miR-361-3p an optimal target for the prevention and intervention in HCC.

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