898 resultados para Cohort study


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Background: Randomised controlled trials have demonstrated significant reductions in colorectal cancer (CRC) incidence and mortality associated with polypectomy. However, little is known about whether polypectomy is effective at reducing CRC risk in routine clinical practice. The aim of this investigation was to quantify CRC risk following polypectomy in a large prospective population-based cohort study.

Methods: Patients with incident colorectal polyps between 2000 and 2005 in Northern Ireland (NI) were identified via electronic pathology reports received to the NI Cancer Registry (NICR). Patients were matched to the NICR to detect CRC and deaths up to 31st December 2010. CRC standardised incidence ratios (SIRs) were calculated and Cox proportional hazards modelling applied to determine CRC risk.

Results: During 44,724 person-years of follow-up, 193 CRC cases were diagnosed amongst 6,972 adenoma patients, representing an annual progression rate of 0.43%. CRC risk was significantly elevated in patients who had an adenoma removed (SIR 2.85; 95% CI: 2.61 to 3.25) compared with the general population. Male sex, older age, rectal site and villous architecture were associated with an increased CRC risk in adenoma patients. Further analysis suggested that not having a full colonoscopy performed at, or following, incident polypectomy contributed to the excess CRC risk.

Conclusions: CRC risk was elevated in individuals following polypectomy for adenoma, outside of screening programmes.

Impact: This finding emphasises the need for full colonoscopy and adenoma clearance, and appropriate surveillance, after endoscopic diagnosis of adenoma.

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Introduction: In this cohort study, we explored the relationship between fluid balance, intradialytic hypotension and outcomes in critically ill patients with acute kidney injury (AKI) who received renal replacement therapy (RRT).

Methods: We analysed prospectively collected registry data on patients older than 16 years who received RRT for at least two days in an intensive care unit at two university-affiliated hospitals. We used multivariable logistic regression to determine the relationship between mean daily fluid balance and intradialytic hypotension, both over seven days following RRT initiation, and the outcomes of hospital mortality and RRT dependence in survivors.

Results: In total, 492 patients were included (299 male (60.8%), mean (standard deviation (SD)) age 62.9 (16.3) years); 251 (51.0%) died in hospital. Independent risk factors for mortality were mean daily fluid balance (odds ratio (OR) 1.36 per 1000 mL positive (95% confidence interval (CI) 1.18 to 1.57), intradialytic hypotension (OR 1.14 per 10% increase in days with intradialytic hypotension (95% CI 1.06 to 1.23)), age (OR 1.15 per five-year increase (95% CI 1.07 to 1.25)), maximum sequential organ failure assessment score on days 1 to 7 (OR 1.21 (95% CI 1.13 to 1.29)), and Charlson comorbidity index (OR 1.28 (95% CI 1.14 to 1.44)); higher baseline creatinine (OR 0.98 per 10 mu mol/L (95% CI 0.97 to 0.996)) was associated with lower risk of death. Of 241 hospital survivors, 61 (25.3%) were RRT dependent at discharge. The only independent risk factor for RRT dependence was pre-existing heart failure (OR 3.13 (95% CI 1.46 to 6.74)). Neither mean daily fluid balance nor intradialytic hypotension was associated with RRT dependence in survivors. Associations between these exposures and mortality were similar in sensitivity analyses accounting for immortal time bias and dichotomising mean daily fluid balance as positive or negative. In the subgroup of patients with data on pre-RRT fluid balance, fluid overload at RRT initiation did not modify the association of mean daily fluid balance with mortality.

Conclusions: In this cohort of patients with AKI requiring RRT, a more positive mean daily fluid balance and intradialytic hypotension were associated with hospital mortality but not with RRT dependence at hospital discharge in survivors.

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Background
Among clinical trials of interventions that aim to modify time spent on mechanical ventilation for critically ill patients there is considerable inconsistency in chosen outcomes and how they are measured. The Core Outcomes in Ventilation Trials (COVenT) study aims to develop a set of core outcomes for use in future ventilation trials in mechanically ventilated adults and children.

Methods/design
We will use a mixed methods approach that incorporates a randomised trial nested within a Delphi study and a consensus meeting. Additionally, we will conduct an observational cohort study to evaluate uptake of the core outcome set in published studies at 5 and 10 years following core outcome set publication. The three-round online Delphi study will use a list of outcomes that have been reported previously in a review of ventilation trials. The Delphi panel will include a range of stakeholder groups including patient support groups. The panel will be randomised to one of three feedback methods to assess the impact of the feedback mechanism on subsequent ranking of outcomes. A final consensus meeting will be held with stakeholder representatives to review outcomes.

Discussion
The COVenT study aims to develop a core outcome set for ventilation trials in critical care, explore the best Delphi feedback mechanism for achieving consensus and determine if participation increases use of the core outcome set in the long term.

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Aims: Cataract surgery is one of the most common surgeries performed, but its overuse has been reported. The threshold for cataract surgery has become increasingly lenient; therefore, the selection process and surgical need has been questioned. The aim of this study was to evaluate the changes associated with cataract surgery in patient-reported vision-related quality of life (VR-QoL).

Methods: A prospective cohort study was conducted. Consecutive patients referred to cataract clinics in an NHS unit in Scotland were identified. Those listed for surgery were invited to complete a validated questionnaire (TyPE) to measure VR-QoL pre- and post-operatively. TyPE has five different domains (near vision, distance vision, daytime driving, night-time driving, and glare) and a global score of vision. The influence of pre-operative visual acuity (VA) levels, vision, and lens status of the fellow eye on changes in VR-QoL were explored. 

Results: A total of 320 listed patients were approached, of whom 36 were excluded. Among the 284 enrolled patients, 229 (81%) returned the questionnaire after surgery. Results revealed that the mean overall vision improved, as reported by patients. Improvements were also seen in all sub-domains of the questionnaire.

Conclusion: The majority of patients appear to have improvement in patient-reported VR-QoL, including those with good pre-operative VA and previous surgery to the fellow eye. VA thresholds may not capture the effects of the quality of life on patients. This information can assist clinicians to make more informed decisions when debating over the benefits of listing a patient for cataract extraction.

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PURPOSE: To investigate whether statins used after colorectal cancer diagnosis reduce the risk of colorectal cancer-specific mortality in a cohort of patients with colorectal cancer.

PATIENTS AND METHODS: A cohort of 7,657 patients with newly diagnosed stage I to III colorectal cancer were identified from 1998 to 2009 from the National Cancer Data Repository (comprising English cancer registry data). This cohort was linked to the United Kingdom Clinical Practice Research Datalink, which provided prescription records, and to mortality data from the Office of National Statistics (up to 2012) to identify 1,647 colorectal cancer-specific deaths. Time-dependent Cox regression models were used to calculate hazard ratios (HR) for cancer-specific mortality and 95% CIs by postdiagnostic statin use and to adjust these HRs for potential confounders.

RESULTS: Overall, statin use after a diagnosis of colorectal cancer was associated with reduced colorectal cancer-specific mortality (fully adjusted HR, 0.71; 95% CI, 0.61 to 0.84). A dose-response association was apparent; for example, a more marked reduction was apparent in colorectal cancer patients using statins for more than 1 year (adjusted HR, 0.64; 95% CI, 0.53 to 0.79). A reduction in all-cause mortality was also apparent in statin users after colorectal cancer diagnosis (fully adjusted HR, 0.75; 95% CI, 0.66 to 0.84).

CONCLUSION: In this large population-based cohort, statin use after diagnosis of colorectal cancer was associated with longer rates of survival.

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BACKGROUND: Asthma management guidelines advocate a stepwise approach to asthma therapy, including the addition of a long-acting bronchodilator to inhaled steroid therapy at step 3. This is almost exclusively prescribed as inhaled combination therapy.

AIMS: To examine whether asthma prescribing practice for inhaled combination therapy (inhaled corticosteroid/long-acting β2-agonist (ICS/LABA)) in primary care in Northern Ireland is in line with national asthma management guidelines.

METHODS: Using data from the Northern Ireland Enhanced Prescribing Database, we examined initiation of ICS/LABA in subjects aged 5-35 years in 2010.

RESULTS: A total of 2,640 subjects (67%) had no inhaled corticosteroid monotherapy (ICS) in the study year or six months of the preceding year (lead-in period) and, extending this to a 12-month lead-in period, 52% had no prior ICS. 41% of first prescriptions for ICS/LABA were dispensed in January to March. Prior to ICS/LABA prescription, in the previous six months only 17% had a short-acting β2-agonist (SABA) dispensed, 5% received oral steroids, and 17% received an antibiotic.

CONCLUSIONS: ICS/LABA therapy was initiated in the majority of young subjects with asthma without prior inhaled steroid therapy. Most prescriptions were initiated in the January to March period. However, the prescribing of ICS/LABA did not appear to be driven by asthma symptoms (17% received SABA in the previous 6 months) or severe asthma exacerbation (only 5% received oral steroids). Significant reductions in ICS/LABA, with associated cost savings, would occur if the asthma prescribing guidelines were followed in primary care.

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Preclinical evidence suggests that metformin could delay cancer progression. Previous epidemiological studies however have been limited by small sample sizes and certain time-related biases. This study aimed to investigate whether colorectal cancer patients with type 2 diabetes who were exposed to metformin had reduced cancer-specific mortality. We conducted a retrospective cohort study of 1,197 colorectal cancer patients newly diagnosed from 1998 to 2009 (identified from English cancer registries) with type 2 diabetes (based upon Clinical Practice Research Datalink, CPRD, prescription and diagnosis records). In this cohort 382 colorectal cancer-specific deaths occurred up to 2012 from the Office of National Statistics (ONS) mortality data. Metformin use was identified from CPRD prescription records. Using time-dependent Cox regression models, unadjusted and adjusted hazard ratios (HR) and 95% CIs were calculated for the association between post-diagnostic exposure to metformin and colorectal cancer-specific mortality. Overall, there was no evidence of an association between metformin use and cancer-specific death before or after adjustment for potential confounders (adjusted HR 1.06, 95% CI 0.80, 1.40). In addition, after adjustment for confounders, there was also no evidence of associations between other diabetic medications and cancer-specific mortality including sulfonylureas (HR 1.14, 95% CI 0.86, 1.51), insulin use (HR 1.35, 95% CI 0.95, 1.93) or other anti-diabetic medications including thiazolidinediones (HR 0.73, 95% CI 0.46, 1.14). Similar associations were observed by duration of use and for all-cause mortality. This population-based study, the largest to date, does not support a protective association between metformin and survival in colorectal cancer patients.

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This study examined the association between moderate drinking at age 16 (adolescence) and alcohol consumption at age 26 (young adulthood), whilst controlling for possible confounding effects at the individual and family level (assessed at birth and age 10). Using the British Cohort Study (BCS70), 6515 respondents provided data on their adolescent alcohol consumption and other behaviours. Of these, 4392 also completed the survey at age 26. Consumption patterns established in adolescence persisted, to a large degree, into early adulthood. Those adolescents who drank moderately in adolescence drank significantly less in adulthood than those adolescents who drank to heavy or hazardous levels. Implications for health promotion strategies and guidance are discussed.

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BACKGROUND: Understanding the heterogeneous genotypes and phenotypes of prostate cancer is fundamental to improving the way we treat this disease. As yet, there are no validated descriptions of prostate cancer subgroups derived from integrated genomics linked with clinical outcome.

METHODS: In a study of 482 tumour, benign and germline samples from 259 men with primary prostate cancer, we used integrative analysis of copy number alterations (CNA) and array transcriptomics to identify genomic loci that affect expression levels of mRNA in an expression quantitative trait loci (eQTL) approach, to stratify patients into subgroups that we then associated with future clinical behaviour, and compared with either CNA or transcriptomics alone.

FINDINGS: We identified five separate patient subgroups with distinct genomic alterations and expression profiles based on 100 discriminating genes in our separate discovery and validation sets of 125 and 103 men. These subgroups were able to consistently predict biochemical relapse (p = 0.0017 and p = 0.016 respectively) and were further validated in a third cohort with long-term follow-up (p = 0.027). We show the relative contributions of gene expression and copy number data on phenotype, and demonstrate the improved power gained from integrative analyses. We confirm alterations in six genes previously associated with prostate cancer (MAP3K7, MELK, RCBTB2, ELAC2, TPD52, ZBTB4), and also identify 94 genes not previously linked to prostate cancer progression that would not have been detected using either transcript or copy number data alone. We confirm a number of previously published molecular changes associated with high risk disease, including MYC amplification, and NKX3-1, RB1 and PTEN deletions, as well as over-expression of PCA3 and AMACR, and loss of MSMB in tumour tissue. A subset of the 100 genes outperforms established clinical predictors of poor prognosis (PSA, Gleason score), as well as previously published gene signatures (p = 0.0001). We further show how our molecular profiles can be used for the early detection of aggressive cases in a clinical setting, and inform treatment decisions.

INTERPRETATION: For the first time in prostate cancer this study demonstrates the importance of integrated genomic analyses incorporating both benign and tumour tissue data in identifying molecular alterations leading to the generation of robust gene sets that are predictive of clinical outcome in independent patient cohorts.

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Background
Preclinical evidence suggests that aspirin may inhibit lung cancer progression. In a large cohort of lung cancer patients, we investigated whether low-dose aspirin use was associated with a reduction in the risk of lung cancer-specific mortality.

Methods
We identified lung cancer patients from English cancer registries diagnosed between 1998 to 2009 from the National Cancer Data Repository. Medication usage was obtained from linkages to the UK Clinical Practice Research Datalink and lung cancer-specific deaths were identified from Office of National Statistics mortality data. Hazard ratios (HR) and 95 % confidence intervals (CI) for the association between low-dose aspirin use (before and after diagnosis) and risk of lung cancer-specific mortality were calculated using Cox regression models.

Results
A total of 14,735 lung cancer patients were identified during the study period. In analysis of 3,635 lung cancer patients, there was no suggestion of an association between low-dose aspirin use after diagnosis and cancer-specific mortality (adjusted HR = 0.96, 95 % CI: 0.85, 1.09). Similarly, no association was evident for low-dose aspirin use before diagnosis and cancer-specific mortality (adjusted HR = 1.00, 95 % CI: 0.95, 1.05). Associations were comparable by duration of use and for all-cause mortality.

Conclusion
Overall, we found little evidence of a protective association between low-dose aspirin use and cancer-specific mortality in a large population-based lung cancer cohort.

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Objectives: To identify factors associated with root caries development during a two year period in a population of independently living older adults. Methods: A prospective cohort study was carried out with 334 independently living volunteers aged 65 and older. At baseline (t0), each participant completed a questionnaire which recorded age, gender, medical history, fluoride exposure, oral and denture hygiene practices, smoking and alcohol consumption, diet information, and socio economic information. Clinical examinations were performed and stimulated saliva samples were collected. Patients were reviewed 12(t1) and 24(t2) months later to determine the root caries increment. Results: 307 adults were assessed at t1 and 280 were assessed at t2 with 83.8% of participants examined at 24 months. Incidence of root caries in this cohort was 17.4% at t1 and 21.6% at t2. The mean root caries increment was 0.43 (SD 1.45) surfaces at t1 and 0.70 (SD 1.86) surfaces at t2. Age >70 years, completing education at primary level, poor oral hygiene, xerostomia, coronal decay at baseline, higher root caries index at baseline and number of exposed root surfaces showed a statistically significant association (P < 0.05) with root caries development. Conclusion: Root caries is a substantive dental health problem for our older population. Root caries prevention strategies should be targeted at older adults who have poor plaque control and high levels of caries experience. In particular patients with xerostomia should be targeted with preventive measures.

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PURPOSE: Concerns were raised about the safety of antiplatelet thienopyridine derivatives after a randomized control trial reported increased risks of cancer and cancer deaths in prasugrel users. We investigate whether clopidogrel, a widely used thienopyridine derivative, was associated with increased risk of cancer-specific or all-cause mortality in cancer patients.

METHODS: Colorectal, breast and prostate cancer patients, newly diagnosed from 1998 to 2009, were identified from the National Cancer Data Repository. Cohorts were linked to the UK Clinical Practice Research Datalink, providing prescription records, and to the Office of National Statistics mortality data (up to 2012). Unadjusted and adjusted hazard ratios (HRs) for cancer-specific and all-cause mortality in post-diagnostic clopidogrel users were calculated using time-dependent Cox regression models.

RESULTS: The analysis included 10 359 colorectal, 17 889 breast and 13 155 prostate cancer patients. There was no evidence of an increase in cancer-specific mortality in clopidogrel users with colorectal (HR = 0.98 95% confidence interval (CI) 0.77, 1.24) or prostate cancer (HR = 1.03 95%CI 0.82, 1.28). There was limited evidence of an increase in breast cancer patients (HR = 1.22 95%CI 0.90, 1.65); however, this was attenuated when removing prescriptions in the year prior to death.

CONCLUSIONS: This novel study of large population-based cohorts of colorectal, breast and prostate cancer patients found no evidence of an increased risk of cancer-specific mortality among colorectal, breast and prostate cancer patients using clopidogrel.

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BACKGROUND: Preclinical studies have shown that statins, particularly simvastatin, can prevent growth in breast cancer cell lines and animal models. We investigated whether statins used after breast cancer diagnosis reduced the risk of breast cancer-specific, or all-cause, mortality in a large cohort of breast cancer patients.

METHODS: A cohort of 17,880 breast cancer patients, newly diagnosed between 1998 and 2009, was identified from English cancer registries (from the National Cancer Data Repository). This cohort was linked to the UK Clinical Practice Research Datalink, providing prescription records, and to the Office of National Statistics mortality data (up to 2013), identifying 3694 deaths, including 1469 deaths attributable to breast cancer. Unadjusted and adjusted hazard ratios (HRs) for breast cancer-specific, and all-cause, mortality in statin users after breast cancer diagnosis were calculated using time-dependent Cox regression models. Sensitivity analyses were conducted using multiple imputation methods, propensity score methods and a case-control approach.

RESULTS: There was some evidence that statin use after a diagnosis of breast cancer had reduced mortality due to breast cancer and all causes (fully adjusted HR = 0.84 [95% confidence interval = 0.68-1.04] and 0.84 [0.72-0.97], respectively). These associations were more marked for simvastatin 0.79 (0.63-1.00) and 0.81 (0.70-0.95), respectively.

CONCLUSIONS: In this large population-based breast cancer cohort, there was some evidence of reduced mortality in statin users after breast cancer diagnosis. However, these associations were weak in magnitude and were attenuated in some sensitivity analyses.

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BACKGROUND:

Digoxin has been shown to affect a number of pathways that are of relevance to cancer, and its use has been associated with increased risks of breast and uterus cancer and, more recently, a 40% increase in colorectal cancer risk. These findings raise questions about the safety of digoxin use in colorectal cancer patients, and, therefore, we investigated whether digoxin use after colorectal cancer diagnosis increased the risk of colorectal cancer-specific mortality.

METHODS:

A cohort of 10,357 colorectal cancer patients newly diagnosed from 1998 to 2009 was identified from English cancer registries and linked to the UK Clinical Practice Research Datalink (to provide digoxin and other prescription records) and to the Office of National Statistics mortality data (to identify 2,724 colorectal cancer-specific deaths). Using time-dependent Cox regression models, unadjusted and adjusted HRs and 95% confidence intervals (CI) were calculated for the association between postdiagnostic exposure to digoxin and colorectal cancer-specific mortality.

RESULTS:

Overall, 682 (6%) colorectal cancer patients used digoxin after diagnosis. Digoxin use was associated with a small increase in colorectal cancer-specific mortality before adjustment (HR, 1.25; 95% CI, 1.07-1.46), but after adjustment for confounders, the association was attenuated (adjusted HR, 1.10; 95% CI, 0.91-1.34) and there was no evidence of a dose response.

CONCLUSIONS:

In this large population-based colorectal cancer cohort, there was little evidence of an increase in colorectal cancer-specific mortality with digoxin use after diagnosis.

IMPACT:

These results provide some reassurance that digoxin use is safe in colorectal cancer patients.

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PURPOSE: In this prospective, multicenter, 14-day inception cohort study, we investigated the epidemiology, patterns of infections, and outcome in patients admitted to the intensive care unit (ICU) as a result of severe acute respiratory infections (SARIs). METHODS: All patients admitted to one of 206 participating ICUs during two study weeks, one in November 2013 and the other in January 2014, were screened. SARI was defined as possible, probable, or microbiologically confirmed respiratory tract infection with recent onset dyspnea and/or fever. The primary outcome parameter was in-hospital mortality within 60 days of admission to the ICU. RESULTS: Among the 5550 patients admitted during the study periods, 663 (11.9 %) had SARI. On admission to the ICU, Gram-positive and Gram-negative bacteria were found in 29.6 and 26.2 % of SARI patients but rarely atypical bacteria (1.0 %); viruses were present in 7.7 % of patients. Organ failure occurred in 74.7 % of patients in the ICU, mostly respiratory (53.8 %), cardiovascular (44.5 %), and renal (44.6 %). ICU and in-hospital mortality rates in patients with SARI were 20.2 and 27.2 %, respectively. In multivariable analysis, older age, greater severity scores at ICU admission, and hematologic malignancy or liver disease were independently associated with an increased risk of in-hospital death, whereas influenza vaccination prior to ICU admission and adequate antibiotic administration on ICU admission were associated with a lower risk. CONCLUSIONS: Admission to the ICU for SARI is common and associated with high morbidity and mortality rates. We identified several risk factors for in-hospital death that may be useful for risk stratification in these patients.