891 resultados para proportional hazards


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To determine whether immunocomplexes (ICs) containing advanced glycation end product (AGE)-LDL (AGE-LDL) and oxidized LDL (oxLDL) contribute to the development of retinopathy over a 16-year period in subjects with type 1 diabetes.

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Objective: To investigate the effect of socioeconomic deprivation on cornea graft survival in the United Kingdom.

Design: Retrospective cohort study.

Participants: All the recipients (n = 13?644) undergoing their first penetrating keratoplasty (PK) registered on the United Kingdom Transplant Registry between April 1999 and March 2011 were included.

Methods: Data of patients' demographic details, indications, graft size, corneal vascularization, surgical complication, rejection episodes, and postoperative medication were collected at the time of surgery and 1, 2, and 5 years postoperatively. Patients with endophthalmitis were excluded from the study. Patients' home postcodes were used to determine the socioeconomic status using a well-validated deprivation index in the United Kingdom: A Classification of Residential Neighborhoods (ACORN). Kaplan–Meier survival and Cox proportional hazards regression were used to evaluate the influence of ACORN categories on 5-year graft survival, and the Bonferroni method was used to adjust for multiple comparisons.

Main Outcome Measures: Patients' socioeconomic deprivation status and corneal graft failure.

Results: A total of 13?644 patients received their first PK during the study periods. A total of 1685 patients (13.36%) were lost to follow-up, leaving 11?821 patients (86.64%) for analysis. A total of 138 of the 11?821 patients (1.17%) developed endophthalmitis. The risk of graft failure within 5 years for the patients classified as hard-pressed was 1.3 times that of the least deprived (hazard ratio, 1.3; 95% confidence interval, 1.1–1.5; P = 0.003) after adjusting for confounding factors and indications. There were no statistically significant differences between the causes of graft failure and the level of deprivation (P = 0.14).

Conclusions: Patients classified as hard-pressed had an increased risk of graft failure within 5 years compared with the least deprived patients.

Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article

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Objective: The incidence of oesophageal adenocarcinoma (EAC) has increased rapidly over the past 40 years and accumulating evidence suggests that obesity, as measured by body mass index (BMI), is a major risk factor. It remains unclear whether abdominal obesity is associated with EAC and gastric adenocarcinoma.

Design: Cox proportional hazards regression was used to examine associations between overall and abdominal obesity with EAC and gastric adenocarcinoma among 218 854 participants in the prospective NIHeAARP cohort.

Results: 253 incident EAC, 191 gastric cardia adenocarcinomas and 125 gastric non-cardia adenocarcinomas accrued to the cohort. Overall obesity (BMI) was positively associated with EAC and gastric
cardia adenocarcinoma risk (highest ($35 kg/m2) vs referent (18.5e<25 kg/m2); HR 2.11, 95% CI 1.09 to 4.09 and HR 3.67, 95% CI 2.00 to 6.71, respectively). Waist circumference was also positively associated with EAC and gastric cardia adenocarcinoma risk (highest vs referent; HR 2.01, 95% CI 1.35 to 3.00 and HR 2.22, 95% CI 1.43 to 3.47, respectively), whereas waist-to-hip ratio (WHR) was positively associated with EAC risk only (highest vs referent; HR 1.81, 95% CI 1.24 to 2.64) and persisted in patients with normal BMI (18.5e<25 kg/m2). Mutual adjustment of WHR and BMI attenuated
both, but did not eliminate the positive associations for either with risk of EAC. In contrast, the majority of the anthropometric variables were not associated with adenocarcinomas of the gastric non-cardia.

Conclusion Overall obesity was associated with a higher risk of EAC and gastric cardia adenocarcinoma, whereas abdominal obesity was found to be associated with increased EAC risk; even in people with normal BMI

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Endometrial cancer risk has been directly associated with glycemic load. However, few studies have investigated this link, and the etiological role of specific dietary carbohydrate components remains unclear. Our aim was to investigate associations of carbohydrate intake, glycemic index, and glycemic load with endometrial cancer risk in the US Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Recruitment took place in 1993-2001. Over a median of 9.0 years of follow-up through 2009, 386 women developed endometrial cancer among 36,115 considered in the analysis. Dietary intakes were assessed using a 124-item diet history questionnaire. Cox proportional hazards models were applied to calculate hazard ratios and 95% confidence intervals. Significant inverse associations were detected between endometrial cancer risk and total available carbohydrate intake (hazard ratio (HR) = 0.66, 95% confidence interval (CI): 0.49, 0.90), total sugars intake (HR = 0.71, 95% CI: 0.52, 0.96), and glycemic load (HR = 0.63, 95% CI: 0.46, 0.84) when women in the highest quartile of intake were compared with those in the lowest. These inverse associations were strongest among overweight and obese women. No associations with endometrial cancer risk were observed for glycemic index or dietary fiber. Our findings contrast with previous evidence and suggest that high carbohydrate intakes and glycemic loads are protective against endometrial cancer development. Further clarification of these associations is warranted.

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BACKGROUND:

Many studies have suggested that caregiving has a detrimental impact on health. However, these conclusions are challenged by research which finds evidence of a comparative survivorship advantage, as well as work which controls for group differences in the demand for care.

METHODS:

We use a large record linkage study of England and Wales to investigate the mortality risks of carers identified in the 2001 Census. The analysis focuses on individuals aged 35-74 living with others in private households and a distinction is made between those providing 1-19 and 20 or more hours of care per week. Logit models identify differences in carers' health at baseline and postcensal survival is analysed using Cox proportional hazards models.

RESULTS:

12.2% of study members reported providing 1-19 h of care and 5.4% reported providing 20 or more hours. While carers were significantly more likely to report poorer health at baseline, survival analyses suggested that they were at a significantly lower risk of dying. This comparative advantage also held when the analyses were restricted to individuals living with at least one person with poor health.

CONCLUSIONS:

The comparative mortality advantage revealed in this analysis challenges common characterisations of carers' health and draws attention to important differences in the way carers are defined in existing analyses. The survival results are consistent with work using similar data for Northern Ireland. However, the study also affords more uniform conclusions about carers' baseline health and this provides grounds for questioning existing hypotheses about the reasons for this advantage.

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Background: Durkheim’s seminal historical study demonstrated that religious affiliation reduces suicide risk, but it is unclear whether this protective effect persists in modern, more secular societies.

Aims: To examine suicide risk according to Christian religious affiliation and by inference to examine underlying mechanisms for suicide risk. If church attendance is important, risk should be lowest for Roman Catholics and highest for those with no religion; if religiosity is important, then ‘conservative’ Christians should fare best.

Method: A 9-year study followed 1 106 104 people aged 16–74 years at the 2001 UK census, using Cox proportional hazards models adjusted for census-based cohort attributes.

Results: In fully adjusted models analysing 1119 cases of suicide, Roman Catholics, Protestants and those professing no religion recorded similar risks. The risk associated with conservative Christians was lower than that for Catholics (HR = 0.71, 95% CI 0.52–0.97).

Conclusions: The relationship between religious affiliation and suicide established by Durkheim may not pertain in societies where suicide rates are highest at younger ages. Risks are similar for those with and without a religious affiliation, and Catholics (who traditionally are characterised by higher levels of church attendance) do not demonstrate lower risk of suicide. However, religious affiliation is a poor measure of religiosity, except for a small group of conservative Christians, although their lower risk of suicide may be attributable to factors such as lower risk behaviour and alcohol consumption.

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Background There has been an increasing interest in the health effects of long
working hours, but little empirical evidence to substantiate early
10 case series suggesting an increased mortality risk. The aim of the
current study is to quantify the mortality risk associated with long
working hours and to see if this varies by employment relations and
conditions of occupation.
Methods A census-based longitudinal study of 414 949 people aged 20-59/64
15 years, working at least 35 h/week, subdivided into four occupational
classes (managerial/professional, intermediate, own account workers,
workers in routine occupations) with linkage to deaths records
over the following 8.7 years. Cox proportional hazards models were
used to examine all-cause and cause-specific mortality risk.
20 Results Overall 9.4% of the cohort worked 55 or more h/week, but this
proportion was greater in the senior management and professional
occupations and in those who were self-employed. Analysis of 4447
male and 1143 female deaths showed that hours worked were
associated with an increased risk of all-cause mortality only for
25 men working for more than 55 or more h/week in routine/semiroutine
occupations [adjusted hazard ratios (adjHR) 1.31: 95%
confidence intervals (CIs) 1.11, 1.55)] compared with their peers
working 35–40 h/week. Their equivalent risk of death from cardiovascular
disease was (adjHR 1.49: 95% CIs 1.10, 2.00).
30 Conclusions These findings substantiate and add to the earlier studies indicating
the deleterious impact of long working hours but also suggest that
the effects are moderated by employment relations or conditions of
occupation. The policy implications of these findings are discussed.

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Background: More accurate coronary heart disease (CHD) prediction, specifically in middle-aged men, is needed to reduce the burden of disease more effectively. We hypothesised that a multilocus genetic risk score could refine CHD prediction beyond classic risk scores and obtain more precise risk estimates using a prospective cohort design.

Methods: Using data from nine prospective European cohorts, including 26,221 men, we selected in a case-cohort setting 4,818 healthy men at baseline, and used Cox proportional hazards models to examine associations between CHD and risk scores based on genetic variants representing 13 genomic regions. Over follow-up (range: 5-18 years), 1,736 incident CHD events occurred. Genetic risk scores were validated in men with at least 10 years of follow-up (632 cases, 1361 non-cases). Genetic risk score 1 (GRS1) combined 11 SNPs and two haplotypes, with effect estimates from previous genome-wide association studies. GRS2 combined 11 SNPs plus 4 SNPs from the haplotypes with coefficients estimated from these prospective cohorts using 10-fold cross-validation. Scores were added to a model adjusted for classic risk factors comprising the Framingham risk score and 10-year risks were derived.

Results: Both scores improved net reclassification (NRI) over the Framingham score (7.5%, p = 0.017 for GRS1, 6.5%, p = 0.044 for GRS2) but GRS2 also improved discrimination (c-index improvement 1.11%, p = 0.048). Subgroup analysis on men aged 50-59 (436 cases, 603 non-cases) improved net reclassification for GRS1 (13.8%) and GRS2 (12.5%). Net reclassification improvement remained significant for both scores when family history of CHD was added to the baseline model for this male subgroup improving prediction of early onset CHD events.

Conclusions: Genetic risk scores add precision to risk estimates for CHD and improve prediction beyond classic risk factors, particularly for middle aged men.

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OBJECTIVES: Risk stratification of Barrett's esophagus (BE) patients based on clinical and endoscopic features may help to optimize surveillance practice for esophageal adenocarcinoma (EAC) development. The aim of this study was to investigate patient symptoms and endoscopic features at index endoscopy and risk of neoplastic progression in a large population-based cohort of BE patients.

METHODS: A retrospective review of hospital records relating to incident BE diagnosis was conducted in a subset of patients with specialized intestinal metaplasia from the Northern Ireland BE register. Patients were matched to the Northern Ireland Cancer Registry to identify progressors to EAC or esophageal high-grade dysplasia (HGD). Cox proportional hazards models were applied to evaluate the association between endoscopic features, symptoms, and neoplastic progression risk.

RESULTS: During 27,997 person-years of follow-up, 128 of 3,148 BE patients progressed to develop HGD/EAC. Ulceration within the Barrett's segment, but not elsewhere in the esophagus, was associated with an increased risk of progression (hazard ratio (HR) 1.72; 95% confidence interval (CI): 1.08–2.76). Long-segment BE carried a significant sevenfold increased risk of progression compared with short-segment BE; none of the latter group developed EAC during the study period. Conversely, the absence of reflux symptoms was associated with an increased risk of cancer progression (HR 1.61; 95% CI: 1.05–2.46).

CONCLUSIONS: BE patients presenting with a long-segment BE or Barrett's ulcer have an increased risk of progressing to HGD/EAC and should be considered for more intense surveillance. The absence of reflux symptoms at BE diagnosis is not associated with a reduced risk of malignant progression, and may carry an increased risk of progression.

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Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women. We assessed the efficacy and safety of the aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease.

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Background: Previous research demonstrates various associations between depression, cardiovascular disease (CVD) incidence and mortality, possibly as a result of the different methodologies used to measure depression and analyse relationships. This analysis investigated the association between depression, CVD incidence (CVDI) and mortality from CVD (MCVD), smoking related conditions (MSRC), and all causes (MALL), in a sample data set, where depression was measured using items from a validated questionnaire and using items derived from the factor analysis of a larger questionnaire, and analyses were conducted based on continuous data and grouped data.

Methods: Data from the PRIME Study (N=9798 men) on depression and 10-year CVD incidence and mortality were analysed using Cox proportional hazards models.

Results: Using continuous data, both measures of depression resulted in the emergence of positive associations between depression and mortality (MCVD, MSRC, MALL). Using grouped data, however, associations between a validated measure of depression and MCVD, and between a measure of depression derived from factor analysis and all measures of mortality were lost.

Limitations: Low levels of depression, low numbers of individuals with high depression and low numbers of outcome events may limit these analyses, but levels are usual for the population studied.

Conclusions: These data demonstrate a possible association between depression and mortality but detecting this association is dependent on the measurement used and method of analysis. Different findings based on methodology present clear problems for the elucidation and determination of relationships. The differences here argue for the use of validated scales where possible and suggest against over-reduction via factor analysis and grouping.

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Background: The association between body size and head and neck cancers (HNCA) is unclear, partly because of the biases in case–control studies. Methods: In the prospective NIH–AARP cohort study, 218,854 participants (132,288 men and 86,566 women), aged 50 to 71 years, were cancer free at baseline (1995 and 1996), and had valid anthropometric data. Cox proportional hazards regression was used to examine the associations between body size and HNCA, adjusted for current and past smoking habits, alcohol intake, education, race, and fruit and vegetable consumption, and reported as HR and 95% confidence intervals (CI). Results: Until December 31, 2006, 779 incident HNCAs occurred: 342 in the oral cavity, 120 in the oro- and hypopharynx, 265 in the larynx, 12 in the nasopharynx, and 40 at overlapping sites. There was an inverse association between HNCA and body mass index, which was almost exclusively among current smokers (HR = 0.76 per each 5 U increase; 95% CI, 0.63–0.93), and diminished as initial years of follow-up were excluded. We observed a direct association with waist-to-hip ratio (HR = 1.16 per 0.1 U increase; 95% CI, 1.03–1.31), particularly for cancers of the oral cavity (HR, 1.40; 95% CI, 1.17–1.67). Height was also directly associated with total HNCAs (P = 0.02), and oro- and hypopharyngeal cancers (P < 0.01). Conclusions: The risk of HNCAs was associated inversely with leanness among current smokers, and directly with abdominal obesity and height. Impact: Our study provides evidence that the association between leanness and risk of HNCAs may be due to effect modification by smoking. Cancer Epidemiol Biomarkers Prev; 23(11); 2422–9. ©2014 AACR.

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Background

Chronic kidney disease is now regarded as a risk factor for cardiovascular disease. The impact of occupational or non-occupational physical activity (PA) on moderate decreases of renal function is uncertain.

Objectives

We aimed to identify the potential association of PA (occupational and leisure-time) on early decline of estimated glomerular filtration rate (eGFR) and to determine the potential mediating effect of PA on the relationship between eGFR and heart disease.

Methods

From the PRIME study analyses were conducted in 1058 employed men. Energy expended during leisure, work and commuting was calculated. Linear regression analyses were used to determine the link between types of PA and moderate decrements of eGFR determined with the KDIGO guideline at the baseline assessment. Cox proportional hazards analyses were used to explore the potential effect of PA on the relationship between eGFR and heart disease, ascertained during follow-up over 10 years.

Results

For these employed men, and after adjustment for known confounders of GFR change, more time spent sitting at work was associated with increased risk of moderate decline in kidney function, while carrying objects or being active at work was associated with decreased risk. In contrast, no significant link with leisure PA was apparent. No potential mediating effect of occupational PA was found for the relationship between eGFR and coronary heart disease.

Conclusion

Occupational PA (potential modifiable factors) could provide a dual role on early impairment of renal function, without influence on the relationship between early decrease of e-GFR and CHD risk.

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Obesity has been linked with elevated levels of C-reactive protein (CRP), and both have been associated with increased risk of mortality and cardiovascular disease (CVD). Previous studies have used a single ‘baseline’ measurement and such analyses cannot account for possible changes in these which may lead to a biased estimation of risk. Using four cohorts from CHANCES which had repeated measures in participants 50 years and older, multivariate time-dependent Cox proportional hazards was used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) to examine the relationship between body mass index (BMI) and CRP with all-cause mortality and CVD. Being overweight (≥25–<30 kg/m2) or moderately obese (≥30–<35) tended to be associated with a lower risk of mortality compared to normal (≥18.5–<25): ESTHER, HR (95 % CI) 0.69 (0.58–0.82) and 0.78 (0.63–0.97); Rotterdam, 0.86 (0.79–0.94) and 0.80 (0.72–0.89). A similar relationship was found, but only for overweight in Glostrup, HR (95 % CI) 0.88 (0.76–1.02); and moderately obese in Tromsø, HR (95 % CI) 0.79 (0.62–1.01). Associations were not evident between repeated measures of BMI and CVD. Conversely, increasing CRP concentrations, measured on more than one occasion, were associated with an increasing risk of mortality and CVD. Being overweight or moderately obese is associated with a lower risk of mortality, while CRP, independent of BMI, is positively associated with mortality and CVD risk. If inflammation links CRP and BMI, they may participate in distinct/independent pathways. Accounting for independent changes in risk factors over time may be crucial for unveiling their effects on mortality and disease morbidity.

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Background and Purpose-The aim was to investigate prospectively the all-cause mortality risk up to and after coronary heart disease (CHD) and stroke events in European middle-aged men.

Methods-The study population comprised 10 424 men 50 to 59 years of age recruited between 1991 and 1994 in France (N=7855) and Northern Ireland (N=2747) within the Prospective Epidemiological Study of Myocardial Infarction. Incident CHD and stroke events and deaths from all causes were prospectively registered during the 10-year follow-up. In Cox's proportional hazards regression analysis, CHD and stroke events during follow-up were used as time-dependent covariates.

Results-A total of 769 CHD and 132 stroke events were adjudicated, and 569 deaths up to and 66 after CHD or stroke occurred during follow-up. After adjustment for study country and cardiovascular risk factors, the hazard ratios of all-cause mortality were 1.58 (95% confidence interval 1.18-2.12) after CHD and 3.13 (95% confidence interval 1.98-4.92) after stroke.

Conclusions-These findings support continuous efforts to promote both primary and secondary prevention of cardiovascular disease.