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Fludarabine, High Dose Cytarabine and Granulocyte Colony-Stimulating Factor (FLAG) as Consolidation Chemotherapy in Older Patients with Acute Myeloid Leukemia: A Retrospective Cohort Study

Law KB, Chang KM, Hamzah NA, Ng KH, Ong TC

Indian J Hematol Blood Transfus, 2017 Dec;33(4):483-491.
PMID: 29075058 DOI: 10.1007/s12288-017-0790-3

The study aimed to investigate the effect of consolidation treatment with fludarabine, high-dose cytarabine and granulocyte colony-stimulating factor or FLAG in older AML patients. The study included 41 eligible patients above 54 years old, who received both induction and consolidation chemotherapy for AML from 2008 to 2013. The study cohort had a minimum 24 months follow-up period. Survival analysis was carried out to assess patients' overall survival and disease free survival based on types of consolidation regimens. The consolidation treatment with FLAG exerted a protective effect to both overall survival and disease free survival in older patients. Patients who were consolidated with FLAG regimen had a significant longer overall survival (log-rank, p = 0.0025) and disease free survival (log-rank, p = 0.0026). The median overall survival was longer (18.70 months) with the use of FLAG when compared to non-FLAG group (8.09 months). The median disease free survival was also longer (13.84 months) with use of FLAG when compared to the non-FLAG group (4.44 months). Regression analysis with Cox model yielded hazard ratio of 0.245 (p = 0.0094) in overall survival and 0.217 (p = 0.0068) in disease free survival. The use of FLAG as consolidation treatment was associated with approximately 60-80% reduction in hazard rates. The result was adjusted for age, race and gender in regression analysis. Older AML patients had longer remission and survival when consolidated with FLAG regimen after the induction chemotherapy.

Matched MeSH terms: Proportional Hazards Models
Survival analysis of 272 patients with pancreatic cancer undergoing combined treatment

Cao N, Zhao A, Zhao G, Wang X, Han B, Lin R, et al.

Integr Cancer Ther, 2015 Mar;14(2):133-9.
PMID: 25567328 DOI: 10.1177/1534735414564185

BACKGROUND: In China, traditional Chinese herbal medicine (TCHM) has been widely used for pancreatic cancer. This retrospective, matched case-control study aimed to assess factors affecting the survival time of patients with pancreatic cancer.
METHODS: From 2004 to 2012, a total of 411 patients with pathologically confirmed pancreatic cancer were enrolled, and 272 patients were matched and divided into TCHM and non-TCHM groups (control group) based on received TCHM or not. The match was according to gender, age of onset, radiotherapy, and chemotherapy. Both groups received comprehensive treatments, the TCHM group simultaneously received the TCHM spleen-invigorating compound for more than 3 months. The Cox model was used for prognostic factor analysis and the Kaplan-Meier method for estimating median overall survival (OS) and disease-free survival (DFS).
RESULTS: In 130 patients with advanced pancreatic cancer, COX analysis showed the Karnofsky Performance Scale (KPS; P = .000), radiotherapy (P = .003), and TCHM (P = .001) were independent prognostic factors for OS, with median OS of 12.7 and 9.9 months in TCHM and non-TCHM groups, respectively (hazard ratio [HR] = 0.520; 95% confidence interval [CI] = 0.353-0.766; P = .033). In 142 patients undergoing radical surgery, KPS (P = .000) and TCHM (P = .000) were independent prognostic factors for OS and DFS, median OS was 23.8 and 12.4 months in TCHM and non-TCHM groups, respectively (HR = 0.373; 95% CI = 0.251-0.554; P = .000), and the median DFS was 21.5 and 10.2 months in TCHM and non-TCHM groups, respectively (HR = 0.352; 95% CI = 0.237-0.522; P = .000).
CONCLUSIONS: KPS was an important prognostic factor of pancreatic cancer. Spleen-invigorating compounds could have an effect on improving the prognosis of pancreatic cancer patients.

Matched MeSH terms: Proportional Hazards Models
Fulltext Sedation depth and long-term mortality in mechanically ventilated critically ill adults: a prospective longitudinal multicentre cohort study

Shehabi Y, Chan L, Kadiman S, Alias A, Ismail WN, Tan MA, et al.

Intensive Care Med, 2013 May;39(5):910-8.
PMID: 23344834 DOI: 10.1007/s00134-013-2830-2

PURPOSE: To ascertain the relationship among early (first 48 h) deep sedation, time to extubation, delirium and long-term mortality.
METHODS: We conducted a multicentre prospective longitudinal cohort study in 11 Malaysian hospitals including medical/surgical patients (n = 259) who were sedated and ventilated ≥24 h. Patients were followed from ICU admission up to 28 days in ICU with 4-hourly sedation and daily delirium assessments and 180-day mortality. Deep sedation was defined as Richmond Agitation Sedation Score (RASS) ≤-3.
RESULTS: The cohort had a mean (SD) age of 53.1 (15.9) years and APACHE II score of 21.3 (8.2) with hospital and 180-day mortality of 82 (31.7%) and 110/237 (46.4%). Patients were followed for 2,657 ICU days and underwent 13,836 RASS assessments. Midazolam prescription was predominant compared to propofol, given to 241 (93%) versus 72 (28%) patients (P < 0.0001) for 966 (39.6%) versus 183 (7.5%) study days respectively. Deep sedation occurred in (182/257) 71% patients at first assessment and in 159 (61%) patients and 1,658 (59%) of all RASS assessments at 48 h. Multivariable Cox proportional hazard regression analysis adjusting for a priori assigned covariates including sedative agents, diagnosis, age, APACHE II score, operative, elective, vasopressors and dialysis showed that early deep sedation was independently associated with longer time to extubation [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.89-0.97, P = 0.003], hospital death (HR 1.11, 95% CI 1.05-1.18, P < 0.001) and 180-day mortality (HR 1.09, 95% CI 1.04-1.15, P = 0.002), but not time to delirium (HR 0.98, P = 0.23). Delirium occurred in 114 (44%) of patients.
CONCLUSION: Irrespective of sedative choice, early deep sedation was independently associated with delayed extubation and higher mortality, and thus was a potentially modifiable risk in interventional trials.

Matched MeSH terms: Proportional Hazards Models
The relationship between Helicobacter pylori and oxygen-derived free radicals in the mechanism of duodenal ulceration

Salim AS

Intern. Med., 1993 May;32(5):359-64.
PMID: 8400493

This prospective randomized study investigated the possibility that duodenal ulcer relapse associated with Helicobacter Pylori infection is mediated by oxygen-derived free radicals. To this end, the radical scavengers allopurinol (50 mg 4 times daily) and dimethyl sulphoxide (DMSO, 500 mg 4 times daily) were administered orally. One hundred and forty-six consecutive patients with previous symptomatic endoscopy proven duodenal ulceration, which had been shown endoscopically to have healed in the presence of gastric mucosal infection with Helicobacter Pylori, were randomized to receive for the period of one year either placebo, or cimetidine 400 mg at bedtime, or allopurinol, or DMSO. In one hundred and twenty-six patients evaluable for efficacy, the cumulative relapse at one year was: placebo 47%, cimetidine 24%, allopurinol 6% and DMSO 6%. Cimetidine was significantly effective in preventing the relapse (p < 0.01), however allopurinol and DMSO were superior to cimetidine in this respect (p < 0.05). In the patients who relapsed, ulcer recurrence tended to occur early in those on placebo and cimetidine and to be evenly distributed over the year in those on free radical scavenging therapy. In all groups, ulcer recurrence throughout the maintenance year was more frequently symptomatic than silent. The incidence of infection with Helicobacter Pylori was not influenced by any of the regimens employed and the bacterium was detected with every relapse noted in this study and during the follow-up endoscopy which was carried out at 6 months and at 12 months during the maintenance year. The results suggest that oxygen-derived free radicals are involved in the relapse of duodenal ulceration in patients infected with Helicobacter Pylori.

Matched MeSH terms: Proportional Hazards Models
Fulltext Consumption of nuts and seeds and pancreatic ductal adenocarcinoma risk in the European Prospective Investigation into Cancer and Nutrition

Obón-Santacana M, Luján-Barroso L, Freisling H, Naudin S, Boutron-Ruault MC, Mancini FR, et al.

Int J Cancer, 2020 Jan 01;146(1):76-84.
PMID: 31107546 DOI: 10.1002/ijc.32415

Four epidemiologic studies have assessed the association between nut intake and pancreatic cancer risk with contradictory results. The present study aims to investigate the relation between nut intake (including seeds) and pancreatic ductal adenocarcinoma (PDAC) risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards models were used to estimate hazards ratio (HR) and 95% confidence intervals (95% CI) for nut intake and PDAC risk. Information on intake of nuts was obtained from the EPIC country-specific dietary questionnaires. After a mean follow-up of 14 years, 476,160 participants were eligible for the present study and included 1,283 PDAC cases. No association was observed between consumption of nuts and PDAC risk (highest intake vs nonconsumers: HR, 0.89; 95% CI, 0.72-1.10; p-trend = 0.70). Furthermore, no evidence for effect-measure modification was observed when different subgroups were analyzed. Overall, in EPIC, the highest intake of nuts was not statistically significantly associated with PDAC risk.

Matched MeSH terms: Proportional Hazards Models
Fulltext Coffee and tea consumption and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition

Sen A, Papadimitriou N, Lagiou P, Perez-Cornago A, Travis RC, Key TJ, et al.

Int J Cancer, 2019 Jan 15;144(2):240-250.
PMID: 29943826 DOI: 10.1002/ijc.31634

The epidemiological evidence regarding the association of coffee and tea consumption with prostate cancer risk is inconclusive, and few cohort studies have assessed these associations by disease stage and grade. We examined the associations of coffee (total, caffeinated and decaffeinated) and tea intake with prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 142,196 men, 7,036 incident prostate cancer cases were diagnosed over 14 years of follow-up. Data on coffee and tea consumption were collected through validated country-specific food questionnaires at baseline. We used Cox proportional hazards regression models to compute hazard ratios (HRs) and 95% confidence intervals (CI). Models were stratified by center and age, and adjusted for anthropometric, lifestyle and dietary factors. Median coffee and tea intake were 375 and 106 mL/day, respectively, but large variations existed by country. Comparing the highest (median of 855 mL/day) versus lowest (median of 103 mL/day) consumers of coffee and tea (450 vs. 12 mL/day) the HRs were 1.02 (95% CI, 0.94-1.09) and 0.98 (95% CI, 0.90-1.07) for risk of total prostate cancer and 0.97 (95% CI, 0.79-1.21) and 0.89 (95% CI, 0.70-1.13) for risk of fatal disease, respectively. No evidence of association was seen for consumption of total, caffeinated or decaffeinated coffee or tea and risk of total prostate cancer or cancer by stage, grade or fatality in this large cohort. Further investigations are needed to clarify whether an association exists by different preparations or by concentrations and constituents of these beverages.

Matched MeSH terms: Proportional Hazards Models
Fulltext Gallstones and incident colorectal cancer in a large pan-European cohort study

Ward HA, Murphy N, Weiderpass E, Leitzmann MF, Aglago E, Gunter MJ, et al.

Int J Cancer, 2019 Sep 15;145(6):1510-1516.
PMID: 30585640 DOI: 10.1002/ijc.32090

Gallstones, a common gastrointestinal condition, can lead to several digestive complications and can result in inflammation. Risk factors for gallstones include obesity, diabetes, smoking and physical inactivity, all of which are known risk factors for colorectal cancer (CRC), as is inflammation. However, it is unclear whether gallstones are a risk factor for CRC. We examined the association between history of gallstones and CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a prospective cohort of over half a million participants from ten European countries. History of gallstones was assessed at baseline using a self-reported questionnaire. The analytic cohort included 334,986 participants; a history of gallstones was reported by 3,917 men and 19,836 women, and incident CRC was diagnosed among 1,832 men and 2,178 women (mean follow-up: 13.6 years). Hazard ratios (HR) and 95% confidence intervals (CI) for the association between gallstones and CRC were estimated using Cox proportional hazards regression models, stratified by sex, study centre and age at recruitment. The models were adjusted for body mass index, diabetes, alcohol intake and physical activity. A positive, marginally significant association was detected between gallstones and CRC among women in multivariable analyses (HR = 1.14, 95%CI 0.99-1.31, p = 0.077). The relationship between gallstones and CRC among men was inverse but not significant (HR = 0.81, 95%CI 0.63-1.04, p = 0.10). Additional adjustment for details of reproductive history or waist circumference yielded minimal changes to the observed associations. Further research is required to confirm the nature of the association between gallstones and CRC by sex.

Matched MeSH terms: Proportional Hazards Models
Fulltext Risk of second primary malignancies in women with breast cancer: Results from the European prospective investigation into cancer and nutrition (EPIC)

Ricceri F, Fasanelli F, Giraudo MT, Sieri S, Tumino R, Mattiello A, et al.

Int J Cancer, 2015 Aug 15;137(4):940-8.
PMID: 25650288 DOI: 10.1002/ijc.29462

Women with a diagnosis of breast cancer are at increased risk of second primary cancers, and the identification of risk factors for the latter may have clinical implications. We have followed-up for 11 years 10,045 women with invasive breast cancer from a European cohort, and identified 492 second primary cancers, including 140 contralateral breast cancers. Expected and observed cases and Standardized Incidence Ratios (SIR) were estimated using Aalen-Johansen Markovian methods. Information on various risk factors was obtained from detailed questionnaires and anthropometric measurements. Cox proportional hazards regression models were used to estimate the role of risk factors. Women with breast cancer had a 30% excess risk for second malignancies (95% confidence interval-CI 18-42) after excluding contralateral breast cancers. Risk was particularly elevated for colorectal cancer (SIR, 1.71, 95% CI 1.43-2.00), lymphoma (SIR 1.80, 95% CI 1.31-2.40), melanoma (2.12; 1.63-2.70), endometrium (2.18; 1.75-2.70) and kidney cancers (2.40; 1.57-3.52). Risk of second malignancies was positively associated with age at first cancer, body mass index and smoking status, while it was inversely associated with education, post-menopausal status and a history of full-term pregnancy. We describe in a large cohort of women with breast cancer a 30% excess of second primaries. Among risk factors for breast cancer, a history of full-term pregnancy was inversely associated with the risk of second primary cancer.

Matched MeSH terms: Proportional Hazards Models
Fulltext Alcohol consumption and the risk of renal cancers in the European prospective investigation into cancer and nutrition (EPIC)

Wozniak MB, Brennan P, Brenner DR, Overvad K, Olsen A, Tjønneland A, et al.

Int J Cancer, 2015 Oct 15;137(8):1953-66.
PMID: 25866035 DOI: 10.1002/ijc.29559

Epidemiologic studies have reported that moderate alcohol consumption is inversely associated with the risk of renal cancer. However, there is no information available on the associations in renal cancer subsites. From 1992 through to 2010, 477,325 men and women in the European Prospective Investigation into Cancer and Nutrition cohort were followed for incident renal cancers (n = 931). Baseline and lifetime alcohol consumption was assessed by country-specific, validated dietary questionnaires. Information on past alcohol consumption was collected by lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazard models. In multivariate analysis, total alcohol consumption at baseline was inversely associated with renal cancer; the HR and 95% CI for the increasing categories of total alcohol consumption at recruitment versus the light drinkers category were 0.78 (0.62-0.99), 0.82 (0.64-1.04), 0.70 (0.55-0.90), 0.91 (0.63-1.30), respectively, (ptrend = 0.001). A similar relationship was observed for average lifetime alcohol consumption and for all renal cancer subsites combined or for renal parenchyma subsite. The trend was not observed in hypertensive individuals and not significant in smokers. In conclusion, moderate alcohol consumption was associated with a decreased risk of renal cancer.

Matched MeSH terms: Proportional Hazards Models
Fulltext Fiber intake modulates the association of alcohol intake with breast cancer

Romieu I, Ferrari P, Chajès V, de Batlle J, Biessy C, Scoccianti C, et al.

Int J Cancer, 2017 Jan 15;140(2):316-321.
PMID: 27599758 DOI: 10.1002/ijc.30415

Alcohol intake has been related to an increased risk of breast cancer (BC) while dietary fiber intake has been inversely associated to BC risk. A beneficial effect of fibers on ethanol carcinogenesis through their impact on estrogen levels is still controversial. We investigated the role of dietary fiber as a modifying factor of the association of alcohol and BC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). This study included 334,850 women aged 35-70 years at baseline enrolled in the ten countries of the EPIC study and followed up for 11.0 years on average. Information on fiber and alcohol intake at baseline and average lifetime alcohol intake were calculated from country-specific dietary and lifestyle questionnaires. Hazard ratios (HR) of developing invasive BC according to different levels of alcohol and fiber intake were computed. During 3,670,439 person-years, 11,576 incident BC cases were diagnosed. For subjects with low intake of fiber (<18.5 g/day), the risk of BC per 10 g/day of alcohol intake was 1.06 (1.03-1.08) while among subjects with high intake of fiber (>24.2 g/day) the risk of BC was 1.02 (0.99-1.05) (test for interaction p = 0.011). This modulating effect was stronger for fiber from vegetables. Our results suggest that fiber intake may modulate the positive association of alcohol intake and BC. Alcohol is well known to increase the risk for BC, while a fiber-rich diet has the opposite effect. Here the authors find a significant interaction between both lifestyle factors indicating that high fiber intake can ease the adverse effects associated with alcohol consumption. Consequently, women with high alcohol intake and low fiber intake (<18.5 g/day) had the highest risk for BC. Specific benefits were associated with fibers from vegetable, warranting further investigations into specific fiber sources and their mechanistic interactions with alcohol-induced BC risk.

Matched MeSH terms: Proportional Hazards Models
Fulltext Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Sanikini H, Muller DC, Sophiea M, Rinaldi S, Agudo A, Duell EJ, et al.

Int J Cancer, 2020 Feb 15;146(4):929-942.
PMID: 31050823 DOI: 10.1002/ijc.32386

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5-25 kg/m2 : HR = 1.94, 95% CI: 1.25-3.03) and women (HR = 2.66, 95% CI: 1.15-6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99-6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52-4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35-14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76-18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14-0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32-0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04-3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.

Matched MeSH terms: Proportional Hazards Models
Fulltext Lifetime and baseline alcohol intakes and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition study

Naudin S, Li K, Jaouen T, Assi N, Kyrø C, Tjønneland A, et al.

Int J Cancer, 2018 Aug 15;143(4):801-812.
PMID: 29524225 DOI: 10.1002/ijc.31367

Recent evidence suggested a weak relationship between alcohol consumption and pancreatic cancer (PC) risk. In our study, the association between lifetime and baseline alcohol intakes and the risk of PC was evaluated, including the type of alcoholic beverages and potential interaction with smoking. Within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, 1,283 incident PC (57% women) were diagnosed from 476,106 cancer-free participants, followed up for 14 years. Amounts of lifetime and baseline alcohol were estimated through lifestyle and dietary questionnaires, respectively. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and their 95% confidence interval (CI). Alcohol intake was positively associated with PC risk in men. Associations were mainly driven by extreme alcohol levels, with HRs comparing heavy drinkers (>60 g/day) to the reference category (0.1-4.9 g/day) equal to 1.77 (95% CI: 1.06, 2.95) and 1.63 (95% CI: 1.16, 2.29) for lifetime and baseline alcohol, respectively. Baseline alcohol intakes from beer (>40 g/day) and spirits/liquors (>10 g/day) showed HRs equal to 1.58 (95% CI: 1.07, 2.34) and 1.41 (95% CI: 1.03, 1.94), respectively, compared to the reference category (0.1-2.9 g/day). In women, HR estimates did not reach statistically significance. The alcohol and PC risk association was not modified by smoking status. Findings from a large prospective study suggest that baseline and lifetime alcohol intakes were positively associated with PC risk, with more apparent risk estimates for beer and spirits/liquors than wine intake.

Matched MeSH terms: Proportional Hazards Models
Fulltext Fruit consumption and the risk of bladder cancer: A pooled analysis by the Bladder Cancer Epidemiology and Nutritional Determinants Study

Jochems SHJ, Reulen RC, van Osch FHM, Witlox WJA, Goossens ME, Brinkman M, et al.

Int J Cancer, 2020 Oct 15;147(8):2091-2100.
PMID: 32285440 DOI: 10.1002/ijc.33008

While the association between fruit consumption and bladder cancer risk has been extensively reported, studies have had inadequate statistical power to investigate associations between types of fruit and bladder cancer risk satisfactorily. Fruit consumption in relation to bladder cancer risk was investigated by pooling individual data from 13 cohort studies. Cox regression models with attained age as time scale were used to estimate hazard ratios (HRs) for intakes of total fruit and citrus fruits, soft fruits, stone fruits, tropical fruits, pome fruits and fruit products. Analyses were stratified by sex, smoking status and bladder cancer subtype. During on average 11.2 years of follow-up, 2836 individuals developed incident bladder cancer. Increasing fruit consumption (by 100 g/day) was inversely associated with the risk of bladder cancer in women (HR = 0.92; 95% CI 0.85-0.99). Although in women the association with fruit consumption was most evident for higher-risk nonmuscle invasive bladder cancer (NMIBC; HR = 0.72; 95% CI 0.56-0.92), the test for heterogeneity by bladder cancer subtype was nonsignificant (P-heterogeneity = .14). Increasing fruit consumption (by 100 g/day) was not associated with bladder cancer risk in men (HR = 0.99; 95% CI 0.94-1.03), never smokers (HR = 0.96; 95% CI 0.88-1.05), former smokers (HR = 0.98; 95% CI 0.92-1.05) or current smokers (HR = 0.95; 95% CI 0.89-1.01). The consumption of any type of fruit was not found to be associated with bladder cancer risk (P values > .05). Our study supports no evidence that the consumption of specific types of fruit reduces the risk of bladder cancer. However, increasing total fruit consumption may reduce bladder cancer risk in women.

Matched MeSH terms: Proportional Hazards Models
Fulltext Exogenous hormone use and cutaneous melanoma risk in women: The European Prospective Investigation into Cancer and Nutrition

Cervenka I, Al Rahmoun M, Mahamat-Saleh Y, Fournier A, Boutron-Ruault MC, Severi G, et al.

Int J Cancer, 2020 Jun 15;146(12):3267-3280.
PMID: 31506954 DOI: 10.1002/ijc.32674

Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country-specific self-administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992-2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline-significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00-1.26), with no detected heterogeneity across countries (phomogeneity = 0.42). This risk increased linearly with duration of use (ptrend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97-1.43), which was heterogeneous across countries (phomogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.

Matched MeSH terms: Proportional Hazards Models
Fulltext Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort

Molina-Montes E, Sánchez MJ, Zamora-Ros R, Bueno-de-Mesquita HB, Wark PA, Obon-Santacana M, et al.

Int J Cancer, 2016 Oct 01;139(7):1480-92.
PMID: 27184434 DOI: 10.1002/ijc.30190

Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 865 exocrine pancreatic cancer cases occurred after 11.3 years of follow-up of 477,309 cohort members. Dietary flavonoid and lignan intake was estimated through validated dietary questionnaires and the US Department of Agriculture (USDA) and Phenol Explorer databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using age, sex and center-stratified Cox proportional hazards models, adjusted for energy intake, body mass index (BMI), smoking, alcohol and diabetes status. Our results showed that neither overall dietary intake of flavonoids nor of lignans were associated with pancreatic cancer risk (multivariable-adjusted HR for a doubling of intake = 1.03, 95% CI: 0.95-1.11 and 1.02; 95% CI: 0.89-1.17, respectively). Statistically significant associations were also not observed by flavonoid subclasses. An inverse association between intake of flavanones and pancreatic cancer risk was apparent, without reaching statistical significance, in microscopically confirmed cases (HR for a doubling of intake = 0.96, 95% CI: 0.91-1.00). In conclusion, we did not observe an association between intake of flavonoids, flavonoid subclasses or lignans and pancreatic cancer risk in the EPIC cohort.

Matched MeSH terms: Proportional Hazards Models
Clinical profile, morbidity, and outcome of adult-onset generalized pustular psoriasis: analysis of 102 cases seen in a tertiary hospital in Johor, Malaysia

Choon SE, Lai NM, Mohammad NA, Nanu NM, Tey KE, Chew SF

Int J Dermatol, 2014 Jun;53(6):676-84.
PMID: 23967807 DOI: 10.1111/ijd.12070

BACKGROUND: Generalized pustular psoriasis (GPP) is a severe but rare variant of psoriasis. Our objective is to review the clinical profile, comorbidities, and outcome of patients with GPP.
MATERIALS AND METHODS: A retrospective note review of all patients with adult-onset GPP.
RESULTS: A total of 102 patients with adult-onset GPP were diagnosed between 1989 and November 2011, with a female to male ratio of 2 : 1. The mean age at onset of GPP was 40.9 years (range: 21-81 years). Acute GPP was the most common variant seen (95 cases), followed by four localized variants of GPP and three with annular pustular psoriasis. Fever and painful skin were present in 89% of patients, arthritis in 34.7%, and leukocytosis in 78.4%. Common triggers were systemic steroids (45 cases), pregnancy (17 cases), and upper respiratory tract infections (16 cases). A positive family history of psoriasis and GPP was present in 29% and 11%, respectively. Comorbidities included obesity (42.9%), hypertension (25.7%), hyperlipidemia (25.7%), and diabetes mellitus (23.7%). The mean duration of admission and pustular flare for acute GPP was 10.3 days (range: 3-44 days) and 16 days (range: 7-60 days), respectively. Fifty-four patients responded to systemic retinoid, 21 to methotrexate, eight to cyclosporine, and one to adalimumab, but recurrences were common.
CONCLUSIONS: Our study confirms the poor response of GPP to currently available anti-psoriatic agents, with frequent flare-ups. There is a need for a more effective targeted therapy for this condition.

Matched MeSH terms: Proportional Hazards Models
Fulltext Spatial Variation of Survival for Colorectal Cancer in Malaysia

Ghazali AK, Keegan T, Taylor BM

Int J Environ Res Public Health, 2021 01 25;18(3).
PMID: 33503972 DOI: 10.3390/ijerph18031052

A patient's survival may depend on several known and unknown factors and it may also vary spatially across a region. Socioeconomic status, accessibility to healthcare and other environmental factors are likely to contribute to survival rates. The aim of the study was to model the spatial variation in survival for colorectal cancer patients in Malaysia, accounting for individual and socioeconomic risk factors. We conducted a retrospective study of 4412 colorectal cancer (ICD-10, C18-C20) patients diagnosed from 2008 to 2013 to model survival in CRC patients. We used the data recorded in the database of the Malaysian National Cancer Patient Registry-Colorectal Cancer (NCPR-CRC). Spatial location was assigned based on the patients' central district location, which involves 144 administrative districts of Malaysia. We fitted a parametric proportional hazards model in which the spatially correlated frailties were modelled by a log-Gaussian stochastic process to analyse the spatially referenced survival data, which is also known as a spatial survival model. After controlling for individual and area level characteristics, our findings indicate wide spatial variation in colorectal cancer survival across Malaysia. Better healthcare provision and higher socioeconomic index in the districts where patients live decreased the risk of death from colorectal cancer, but these associations were not statistically significant. Reliable measurement of environmental factors is needed to provide good insight into the effects of potential risk factors for the disease. For example, a better metric is needed to measure socioeconomic status and accessibility to healthcare in the country. The findings provide new information that might be of use to the Ministry of Health in identifying populations with an increased risk of poor survival, and for planning and providing cancer control services.

Matched MeSH terms: Proportional Hazards Models
Fulltext Advanced Stage at Presentation Remains a Major Factor Contributing to Breast Cancer Survival Disparity between Public and Private Hospitals in a Middle-Income Country

Kong YC, Bhoo-Pathy N, Subramaniam S, Bhoo-Pathy N, Taib NA, Jamaris S, et al.

Int J Environ Res Public Health, 2017 04 16;14(4).
PMID: 28420149 DOI: 10.3390/ijerph14040427

Background: Survival disparities in cancer are known to occur between public and private hospitals. We compared breast cancer presentation, treatment and survival between a public academic hospital and a private hospital in a middle-income country. Methods: The demographics, clinical characteristics, treatment and overall survival (OS) of 2767 patients with invasive breast carcinoma diagnosed between 2001 and 2011 in the public hospital were compared with 1199 patients from the private hospital. Results: Compared to patients in the private hospital, patients from the public hospital were older at presentation, and had more advanced cancer stages. They were also more likely to receive mastectomy and chemotherapy but less radiotherapy. The five-year OS in public patients was significantly lower than in private patients (71.6% vs. 86.8%). This difference was largely attributed to discrepancies in stage at diagnosis and, although to a much smaller extent, to demographic differences and treatment disparities. Even following adjustment for these factors, patients in the public hospital remained at increased risk of mortality compared to their counterparts in the private hospital (Hazard Ratio: 1.59; 95% Confidence Interval: 1.36-1.85). Conclusion: Late stage at diagnosis appears to be a major contributing factor explaining the breast cancer survival disparity between public and private patients in this middle-income setting.

Matched MeSH terms: Proportional Hazards Models
The effect of being overweight on cancer incidence and all-cause mortality in Asians: a prospective study in Singapore

Lee J, Wang H, Chia KS, Koh D, Hughes K

Int J Epidemiol, 2002 Aug;31(4):875-6.
PMID: 12177037
Matched MeSH terms: Proportional Hazards Models
Risk factors and incident coronary heart disease in Chinese, Malay and Asian Indian males: the Singapore Cardiovascular Cohort Study

Lee J, Heng D, Chia KS, Chew SK, Tan BY, Hughes K

Int J Epidemiol, 2001 Oct;30(5):983-8.
PMID: 11689508

OBJECTIVE: This prospective study in Singapore investigated the relationships of established coronary risk factors with incident coronary heart disease (CHD) for Chinese, Malay, and Asian Indian males.
SUBJECTS: A cohort (consisting of 2879 males without diagnosed CHD) derived from three previous cross-sectional surveys.
METHODS: Individual baseline data were linked to registry databases to obtain the first event of CHD. Hazard ratios (HR) or relative risks for risk factors were calculated using Cox's proportional hazards model with adjustment for age and ethnic group and adjustment for age, ethnic group and all other risk factors (overall adjusted).
RESULTS: There were 24,986 person-years of follow-up. The overall adjusted HR with 95% CI are presented here. Asian Indians were at greatest risk of CHD, compared to Chinese (3.0; 2.0-4.8) and Malays (3.4; 1.9-3.3). Individuals with hypertension (2.4; 1.6-2.7) or diabetes (1.7; 1.1-2.7) showed a higher risk of CHD. High low density lipoprotein cholesterol (LDL-C) (1.5; 1.0-2.1), high fasting triglyceride (1.5; 0.9-2.6) and low high density lipoprotein cholesterol (HDL-C) (1.3; 0.9-2.0) showed a lesser but still increased risk. Alcohol intake was protective with non-drinkers having an increased risk of CHD (1.8; 1.0-3.3). Obesity (body mass index > or =30) showed an increased risk (1.8; 0.6-5.4). An increased risk of CHD was found in cigarette smokers of > or =20 pack years (1.5; 0.9-2.5) but not with lesser amounts.
CONCLUSIONS: The increased susceptibility of Asian Indian males to CHD has been confirmed in a longitudinal study. All of the examined established risk factors for CHD were found to play important but varying roles in the ethnic groups in Singapore.

Matched MeSH terms: Proportional Hazards Models

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