MicroRNAs as biomarkers for prostate cancer prognosis: a systematic review and a systematic reanalysis of public data

Abstract Background Reliable prognostic biomarkers to distinguish indolent from aggressive prostate cancer (PCa) are lacking. Many studies investigated microRNAs (miRs) as PCa prognostic biomarkers, often reporting inconsistent findings. We present a systematic review of these; also systematic reanalysis of public miR-profile datasets to identify tissue-derived miRs prognostic of biochemical recurrence (BCR) in patients undergoing radical prostatectomy. Methods Independent PubMed searches were performed for relevant articles from January 2007 to December 2019. For the review, 128 studies were included. Pooled-hazard-ratios (HRs) for miRs in multiple studies were calculated using a random-effects model (REM). For the reanalysis, five studies were included and Cox proportional-hazard models, testing miR association with BCR, performed for miRs profiled in all. Results Systematic review identified 120 miRs as prognostic. Five (let-7b-5p, miR-145-5p, miR152-3p, miR-195-5p, miR-224-5p) were consistently associated with progression in multiple cohorts/studies. In the reanalysis, ten (let-7a-5p, miR-148a-3p, miR-203a-3p, miR-26b-5p, miR30a-3p, miR-30c-5p, miR-30e-3p, miR-374a-5p, miR-425-3p, miR-582-5p) were significantly prognostic of BCR. Of these, miR-148a-3p (HR = 0.80/95% CI = 0.68-0.94) and miR-582-5p (HR = 0.73/95% CI = 0.61-0.87) were also reported in prior publication(s) in the review. Conclusions Fifteen miRs were consistently associated with disease progression in multiple publications or datasets. Further research into their biological roles is warranted to support investigations into their performance as prognostic PCa biomarkers.

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Farming tasks and the development of rheumatoid arthritis in the agricultural health study

Occupational and Environmental Medicine ◽

10.1136/oemed-2018-105361 ◽

2019 ◽

pp. oemed-2018-105361 ◽

Cited By ~ 4

Author(s):

Christine G Parks ◽

Armando Meyer ◽

Laura E Beane Freeman ◽

Jonathan Hofmann ◽

Dale P Sandler

Keyword(s):

Rheumatoid Arthritis ◽

Self Report ◽

Health Study ◽

Proportional Hazard ◽

Agricultural Health ◽

Cox Proportional Hazard ◽

Hazard Ratios ◽

Cox Proportional Hazard Models ◽

Agricultural Health Study

ObjectivesFarming has been associated with rheumatoid arthritis (RA). Some studies have evaluated the effects of pesticides, but other agricultural exposures may also affect immune response.MethodsWe investigated non-pesticide agricultural exposures in relation to RA in licensed pesticide applicators (n=27 175, mostly male farmers) and their spouses (n=22 231) in the Agricultural Health Study (AHS) cohort (1993–1997) who completed at least one follow-up survey through 2015. Incident RA cases (n=229 applicators and 249 spouses) were identified based on self-report confirmed by use of disease-modifying antirheumatic drugs or medical records. Hazard Ratios (HRs) and 95% Confidence Intervals (CIs) were estimated by Cox proportional hazard models adjusting for applicator status, state, smoking, education and specific pesticide use, allowing estimates to vary by median age when hazards assumptions were not met.ResultsOverall, RA was associated with regularly applying chemical fertilisers (HR=1.50; 95% CI 1.11 to 2.02), using non-gasoline solvents (HR=1.40; 95% CI 1.09 to 1.80), and painting (HR=1.26; 95% CI 1.00 to 1.59). In older applicators (>62 years), RA was associated with driving combines (HR=2.46; 95% CI 1.05 to 5.78) and milking cows (HR=2.56; 95% CI 1.01 to 6.53). In younger participants (≤62 years), RA was inversely associated with raising animals as well as crops (HR=0.68; 95% CI 0.51 to 0.89 vs crops only). Associations with specific crops varied by age: some (eg, hay) were inversely associated with RA in younger participants, while others (eg, alfalfa) were associated with RA in older participants.ConclusionThese findings suggest several agricultural tasks and exposures may contribute to development of RA.

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HAS FRAILTY SCORE AND FRAILTY LETHALITY CHANGED OVER TIME? HARMONIZATION OF NHANES COHORTS FROM 1999 TO 2016

Innovation in Aging ◽

10.1093/geroni/igz038.2518 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S682-S682

Author(s):

Joanna M Blodgett ◽

Kenneth Rockwood ◽

Olga Theou

Keyword(s):

Multilevel Models ◽

Healthcare Access ◽

Frailty Index ◽

Age Groups ◽

Proportional Hazard ◽

Health And Nutrition ◽

Cox Proportional Hazard ◽

Hazard Ratios ◽

Cox Proportional Hazard Models ◽

Over Time

Abstract Positive advances in life expectancy, healthcare access and medical technology have been accompanied by an increased prevalence of chronic diseases and substantial population ageing. How this impacts changes in both frailty level and subsequent mortality in recent decades are not well understood. We aimed to investigate how these factors changed over an 18-year period. Nine waves of the National Health and Nutrition Examination Survey (1999-2016) were harmonized to create a 46-item frailty index (FI) using self-reported and laboratory-based health deficits. Individuals aged 20+ were included in analyses (n=44086). Mortality was ascertained in December 2015. Weighted multilevel models estimated the effect of cohort on FI score in 10-year age-stratified groups. Cox proportional hazard models estimated if two or four-year mortality risk of frailty changed across the 1999-2012 cohorts. Mean FI score was 0.11±0.10. In the five older age groups (>40 years), later cohorts had higher frailty levels than did earlier cohorts. For example, in people aged 80+, each subsequent cohort had an estimated 0.007 (95%CI: 0.005, 0.009) higher FI score. However, in those aged 20-29, later cohorts had lower frailty [β=-0.0009 (-0.0013, -0.0005)]. Hazard ratios and cohort-frailty interactions indicated that there was no change in two or four-year lethality of FI score over time (i.e. two-year mortality: HR of 1.069 (1.055, 1.084) in 1999-2000 vs 1.061 (1.044, 1.077) in 2011-2012). Higher frailty levels in the most recent years in middle and older aged adults combined with unchanged frailty lethality suggests that the degree of frailty may continue to increase.

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Effectiveness and Safety of Non–Vitamin K Oral Anticoagulants in Comparison to Phenprocoumon: Data from 61,000 Patients with Atrial Fibrillation

Thrombosis and Haemostasis ◽

10.1160/th17-10-0733 ◽

2018 ◽

Vol 118 (03) ◽

pp. 526-538 ◽

Cited By ~ 30

Author(s):

Stefan Hohnloser ◽

Edin Basic ◽

Christopher Hohmann ◽

Michael Nabauer

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Standard Dose ◽

Oral Anticoagulants ◽

Proportional Hazard ◽

Systemic Embolism ◽

Cox Proportional Hazard ◽

Hazard Ratios ◽

Cox Proportional Hazard Models ◽

Baseline Characteristics

AbstractAll pivotal trials have evaluated non–vitamin K oral antagonists (NOACs) against warfarin. However, in some regions of the world, phenprocoumon is the most widely used vitamin K antagonist (VKA). There is little evidence documenting effectiveness and safety of NOACs compared with phenprocoumon in atrial fibrillation (AF). A retrospective cohort study using a German claims database was conducted to assess effectiveness (stroke, systemic embolism [SE]) and safety (bleeding leading to hospitalization) during therapy with NOACs and phenprocoumon in 61,205 AF patients. Hazard ratios (HRs) for effectiveness and safety outcomes were derived from Cox proportional hazard models, adjusting for baseline characteristics. Propensity score matching was performed as a sensitivity analysis. As a prespecified subgroup analysis, the effects of reduced NOAC dosing were compared with phenprocoumon. A total of 61,205 patients were identified in whom phenprocoumon (n = 23,823, 38.9%), apixaban (n = 10,117, 16.5%), dabigatran (n = 5,122, 8.4%), or rivaroxaban (n = 22,143, 36.2%) was initiated. After adjusting for baseline confounders, all three NOACs tested had significantly lower risks of stroke/SE compared with phenprocoumon (apixaban—HR: 0.77, 95% CI: 0.66–0.90; dabigatran—HR: 0.74, 95% CI: 0.60–0.91; rivaroxaban—HR: 0.86, 95% CI: 0.76–0.97). Apixaban (HR: 0.58, 95% CI: 0.49–0.69) and dabigatran (HR: 0.64, 95% CI: 0.50–0.80) were associated with lower bleeding risks than phenprocoumon, whereas the risk was similar for rivaroxaban and phenprocoumon. All three NOACs showed reduced risk of intracranial bleeding compared with phenprocoumon. Reduced doses of NOACs were predominantly used in patients with advanced age and comorbidities with generally similar effectiveness and safety benefits compared with phenprocumon as standard-dose NOACs.

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The Effect of Tegafur-Uracil on Survival in T Categories as Defined in the Eighth Edition of the TNM Classification: An Exploratory Analysis of Postoperative Adjuvant Tegafur-Uracil on Survival in Patients with Adenocarcinoma of the Lung

Chemotherapy ◽

10.1159/000479084 ◽

2017 ◽

Vol 62 (6) ◽

pp. 357-360

Author(s):

Masahiro Tsuboi ◽

Chikuma Hamada ◽

Harubumi Kato ◽

Mitsuo Ohta

Keyword(s):

Tnm Classification ◽

Tumor Diameter ◽

Proportional Hazard ◽

Adenocarcinoma Of The Lung ◽

Proportional Hazard Models ◽

Cox Proportional Hazard ◽

Hazard Ratios ◽

Cox Proportional Hazard Models ◽

Eighth Edition ◽

T Category

Background: Tegafur-uracil (UFT) improves survival in patients with stage I adenocarcinoma of the lung. We evaluated the effect of UFT on survival in maximum primary tumor diameter (T) categories as defined in the eighth edition of the TNM Classification (TNM8). Methods: Tumors were subgrouped on the basis of T category (TNM8) as follows: T1a, T ≤1 cm; T1b, 1 < T ≤2 cm; T1c, 2 < T ≤3 cm; T2a, 3 < T ≤4 cm; T2b , 4 < T ≤5 cm; T3, 5 < T ≤7 cm. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox proportional hazard models. Results: UFT was associated with improved survival. The adjusted HRs were as follows: for T1a, 0.79 (95% CI 0.14-4.50); for T1b, 1.16 (95% CI 0.63-2.12); for T1c, 0.74 (95% CI 0.43-1.27); for T2a, 0.45 (95% CI 0.21-0.96); for T2b, 0.55 (95% CI 0.10-3.07), and for T3, 0.70 (95% CI 0.20-2.50). Conclusions: The adjuvant chemotherapy with UFT tended to improve survival in patients with adenocarcinoma of the lung of each T category based on TNM8, except T1b.

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Periodontitis and the subsequent risk of glaucoma: results from the real-world practice

Scientific Reports ◽

10.1038/s41598-020-74589-6 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Kuo-Ting Sun ◽

Te-Chun Shen ◽

Shih-Chueh Chen ◽

Chia-Ling Chang ◽

Ching‐Hao Li ◽

...

Keyword(s):

High Risk ◽

Open Angle Glaucoma ◽

Research Database ◽

Proportional Hazard ◽

Cox Proportional Hazard ◽

Hazard Ratios ◽

Minimum Age ◽

Cox Proportional Hazard Models ◽

Underlying Mechanisms ◽

Closed Angle

Abstract Periodontitis is a multifactorial inflammatory disease that can cause tooth loss and contribute to systemic inflammation. It is suggested that periodontitis may be associated with the development of glaucoma. Based on data from Taiwan’s National Health Insurance Research Database, a retrospective cohort study was conducted to investigate the risk of developing glaucoma in patients with periodontitis. The periodontitis cohort consisted of newly diagnosed adult patients (n = 194,090, minimum age = 20 years) between 2000 and 2012. The comparison group included age-, gender-, and diagnosis date-matched people without periodontitis (n = 194,090, minimum age = 20 years). Incident glaucoma was monitored until the end of 2013. Hazard ratios (HRs) with confidence intervals (CIs) were established based on the Cox proportional hazard models. The risk of developing glaucoma was higher in patients with periodontitis than those without periodontitis (31.2 vs. 23.3 patients per 10,000 person-years, with an adjusted HR of 1.26 [95% CI 1.21–1.32]). A high risk was evident even after stratifying by age (adjusted HRs = 1.34 [1.26–1.44] for ages 20–49, 1.24 [1.13–1.36] for ages ≥ 65, and 1.20 [1.12–1.29] for ages 50–64 years), sex (adjusted HRs = 1.33 [1.24–1.41] and 1.21 [1.14–1.28] for men and women, respectively), presence of comorbidity (adjusted HRs = 1.38 [1.29–1.47] and 1.18 [1.12–1.25] for without and with comorbidity, respectively), and corticosteroid use (adjusted HRs = 1.27 [1.21–1.33] and 1.21 [1.08–1.35] for without and with corticosteroid use, respectively). Specifically, patients with periodontitis exhibited a significantly high risk of primary open-angle glaucoma (adjusted HR = 1.31 [1.21–1.32]) but not for primary closed-angle glaucoma (adjusted HR = 1.05 [0.94–1.17]). People with periodontitis are at a greater risk of glaucoma than individuals without periodontitis. Ocular health should be emphasized for such patients, and the underlying mechanisms need further investigation.

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Occupation and COVID-19 mortality in England: a national linked data study of 14.3 million adults

10.1101/2021.05.12.21257123 ◽

2021 ◽

Author(s):

Vahe Nafilyan ◽

Piotr Pawelek ◽

Daniel Ayoubkhani ◽

Sarah Rhodes ◽

Lucy Pembrey ◽

...

Keyword(s):

Substantial Contribution ◽

Proportional Hazard ◽

The Public ◽

Work Related ◽

Private Households ◽

Cox Proportional Hazard ◽

Hazard Ratios ◽

Cox Proportional Hazard Models ◽

Workplace Factors ◽

Socio Demographic Factors

Objective: To estimate occupational differences in COVID-19 mortality, and test whether these are confounded by factors, such as regional differences, ethnicity and education or due to non-workplace factors, such as deprivation or pre-pandemic health. Design: Retrospective cohort study Setting: People living in private households England Participants: 14,295,900 people aged 40-64 years (mean age 52 years, 51% female) who were alive on 24 January 2020, living in private households in England in 2019, were employed in 2011, and completed the 2011 census. Main outcome measures: COVID-19 related death, assessed between 24 January 2020 and 28 December 2020. We estimated age-standardised mortality rates per 100,000 person-years at risk (ASMR) stratified by sex and occupations. To estimate the effect of occupation due to work-related exposures, we used Cox proportional hazard models to adjust for confounding (region, ethnicity, education), as well as non-workplace factors that are related to occupation. Results: There is wide variation between occupations in COVID-19 mortality. Several occupations, particularly those involving contact with patients or the public, show three-fold or four-fold risks. These elevated risks were greatly attenuated after adjustment for confounding and mediating non-workplace factors. For example, the hazard ratio (HR) for men working as taxi and cab drivers or chauffeurs changed from 4.60 [95%CI 3.62-5.84] to 1.47 [1.14-1.89] after adjustment. More generally, the overall HR for men working in essential occupations compared with men in non-essential occupations changed from 1.45 [1.34 - 1.56] to 1.22 [1.13 - 1.32] after adjustment. For most occupations, confounding and other mediating factors explained about 70% to 80% of the age-adjusted hazard ratios. Conclusions Working conditions are likely to play a role in COVID-19 mortality, particularly in occupations involving contact with COVID-19 patients or the public. However, there is also a substantial contribution from non-workplace factors, including regional factors, socio-demographic factors, and pre-pandemic health.

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Prescription patterns of dialysate potassium and potassium binders and survival on haemodialysis—the French Renal Epidemiology and Information Network registry

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa077 ◽

2020 ◽

Vol 36 (1) ◽

pp. 151-159 ◽

Cited By ~ 1

Author(s):

Lucile Mercadal ◽

Oriane Lambert ◽

Cécile Couchoud ◽

Marie Metzger ◽

Stéphane Edet ◽

...

Keyword(s):

National Registry ◽

Proportional Hazard ◽

Prescription Patterns ◽

Cox Proportional Hazard ◽

Mortality Hazard ◽

Hazard Ratios ◽

Cox Proportional Hazard Models ◽

Facility Level ◽

Potassium Binders ◽

Almost All

Abstract Background Management of potassium disorders in patients on haemodialysis (HD) is complex. We studied prescription patterns of dialysate potassium and potassium binders, and their associations with patient survival. Methods This national registry-based study included 25 629 incident adult patients alive after 3 months of HD from 2010 through 2013 and followed-up through 31 December 2014. We used Cox proportional hazard models to estimate multiadjusted mortality hazard ratios (HRs) associated with time-dependent exposure to facility-level dialysate potassium concentrations and patient-level potassium binder exposure. Results Almost all dialysis units used, and generally most often, dialysate potassium concentrations of 2 mmol/L. During this period, use of concentrations <2 mmol/L tended to decrease and those ≥3 mmol/L to increase. In 2014, 9% of units used a single dialysate formula, 41% used two and 50% three or more. The most frequent combinations were 2 and 3 mmol/L (40%), and <2, 2 and 3 mmol/L (37%). Compared with patients on HD in units using only one dialysate formula, those in units using two or three had adjusted mortality HRs of 0.91 [95% confidence interval (CI) 0.82–1.01] and 0.84 (0.75–0.93), respectively. Potassium binders were prescribed for 37% of all patients at baseline. Adjusted mortality HRs associated with doses <4, 4–8 and ≥8 g/day versus none were 1.22 (95% CI 1.04–1.51), 0.6 (0.54–0.66) and 0.25 (0.24–0.33), respectively. Conclusions Diversity in facility-level use of dialysate potassium concentrations and potassium binder use at an appropriate dose appear to be associated with better survival in HD patients.

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Wrist circumference as a novel predictor of transition from metabolically healthy to unhealthy phenotype in overweight/obese adults: a gender-stratified 15.5-year follow-up

BMC Public Health ◽

10.1186/s12889-021-12371-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Pouria Mousapour ◽

Maryam Barzin ◽

Majid Valizadeh ◽

Maryam Mahdavi ◽

Farzad Hadaegh ◽

...

Keyword(s):

Predictive Performance ◽

Proportional Hazard ◽

Obese Adults ◽

Cox Proportional Hazard ◽

Hazard Ratios ◽

Wrist Circumference ◽

Cox Proportional Hazard Models ◽

Metabolically Healthy

Abstract Background Individuals with transition from metabolically healthy overweight/obese (MHO) to metabolically unhealthy overweight/obese (MUO) phenotype are significantly predisposed to greater risks of cardiovascular events compared to those with a persistent MHO phenotype. The aim of this study was to evaluate the predictive performance of wrist circumference for this transition in adults over a 15.5-year follow-up. Methods We included 309 males and 821 females with the age of ≥18 years old, body mass index ≥25 kg/m2, and metabolically healthy status according to the criteria of the Joint Interim Statement. The incidence of MUO phenotype was evaluated for each gender, across tertiles wrist circumference, using Cox-proportional hazard models. Results The overall rate of transition from MHO to MUO phenotype was 87.1% in males and 77.5% in females. The hazard ratios (HRs) with 95% CI across second and third tertiles of wrist circumference were 0.89 (0.64-1.24) and 1.31 (0.99-1.73) in men (P for trend =0.027); and 1.34 (1.09-1.66) and 1.61 (1.30-2.00) in women (P for trend <0.001), respectively. After multivariable adjustment, HRs across second and third tertiles of wrist circumference were 0.92 (0.64-1.32) and 1.18 (0.83-1.67) in males (p for trend =0.352), and 1.32 (1.05-1.65) and 1.34 (1.06-1.96) in females (p for trend =0.025), respectively. Conclusions Wrist circumference significantly predicts the transition from MHO to MUO phenotype in adults of both genders. However, it is an independent predictor of the transition only in females. Future studies are warranted to clarify the role of wrist circumference mechanisms on metabolic risk deterioration.

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Association between Pulse Pressure and Onset of Dementia in an Elderly Korean Population: A Cohort Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17051657 ◽

2020 ◽

Vol 17 (5) ◽

pp. 1657 ◽

Cited By ~ 1

Author(s):

Yongku Jung ◽

Dong-Woo Choi ◽

Sohee Park ◽

Sung-In Jang ◽

Eun-Cheol Park

Keyword(s):

Pulse Pressure ◽

Health Policies ◽

Proportional Hazard ◽

Future Health ◽

Rural Regions ◽

South Korean ◽

Cox Proportional Hazard ◽

Hazard Ratios ◽

Cox Proportional Hazard Models ◽

Korean National Health Insurance

Objective: There is paucity of studies on the association between pulse pressure and the development of dementia, although this association has already been established. This study aimed at investigating the association between pulse pressure and the onset of dementia. Methods: We used the South Korean National Health Insurance Service claims cohort data to select 149,663 patients without dementia aged ≥60 years. We calculated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for dementia using Cox proportional hazard models according to a pulse pressure classification (<50, 50–59, 60–69, 70–79, 80–89, or 90+). Results: Compared to women with pulse pressure <50, those with pulse pressures of 50–59, 60–69, and 90+ had higher HRs for dementia (1.14, 1.22, and 1.03, respectively). These associations were particularly strong in those on Medicaid insurance and from rural regions. However, there were no statistically significant results among men. Conclusions: A higher pulse pressure was associated with an elevated risk of dementia in women aged >60 years, particularly those on Medicaid and from rural regions, possibly due to their inability to access hypertension and other medical treatment. The establishment of dementia indicators will help to guide future health policies for the prevention of dementia.

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Androgen-deprivation Therapy and the Risk of newly Developed Fractures in Patients with Prostate Cancer: A Nationwide Cohort Study in Korea

10.21203/rs.3.rs-140143/v1 ◽

2021 ◽

Author(s):

Do Kyung Kim ◽

Jong Won Kim ◽

Hye Sun Lee ◽

Ju-Young Park ◽

Hyun Kyu Ahn ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Deprivation Therapy ◽

Cox Regression ◽

Androgen Deprivation ◽

Proportional Hazard ◽

Cox Regression Analysis ◽

Cox Proportional Hazard ◽

Hazard Ratios ◽

Increased Risk ◽

Cox Proportional Hazard Regression

Abstract Purpose: We evaluated the risk of osteoporosis and fractures associated with androgen deprivation therapy (ADT) use and duration in men with prostate cancer.Methods: From the nationwide claims database in South Korea, a total of 218,203 men with prostate cancer were identified between 2008 and 2017. To adjust for comorbidities between cohorts, 1:1 propensity score matching was used. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of events associated with ADT. Results: In the matched cohort, there were differences in the incidence of newly developed osteoporosis (8.79% in the ADT group vs. 7.08% in the non-ADT group, p < 0.0001) and fractures (8.12% in the ADT group vs. 5.04% in the non-ADT group, p < 0.0001). Age-adjusted Cox regression analysis revealed that the ADT group had a significantly higher risk of osteoporosis (HR, 1.381; 95% CI, 1.305–1.461; p < 0.0001) and fractures (HR, 1.815; 95% CI; 1.703–1.935; p < 0.0001) compared to the non-ADT group. Furthermore, the risk of osteoporosis and fractures increased as the duration of ADT increased.Conclusions: The ADT was associated with an increased risk of osteoporosis and fractures in prostate cancer patients.

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