Chris R Cardwell

Queen's University Belfast, Béal Feirste, N Ireland, United Kingdom

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Publications (106)505.35 Total impact

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    ABSTRACT: Recent laboratory and epidemiological evidence suggests that beta-blockers could inhibit prostate cancer progression. Methods: We investigated the effect of beta-blockers on prostate cancer-specific mortality in a cohort of prostate cancer patients. Prostate cancer patients diagnosed between 1998 and 2006 were identified from the UK Clinical Practice Research Database and confirmed by cancer registries. Patients were followed up to 2011 with deaths identified by the Office of National Statistics. A nested case-control analysis compared patients dying from prostate cancer (cases) with up to three controls alive at the time of their death, matched by age and year of diagnosis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression. Results: Post-diagnostic beta-blocker use was identified in 25% of 1184 prostate cancer-specific deaths and 26% of 3531 matched controls. There was little evidence (P=0.40) of a reduction in the risk of cancer-specific death in beta-blocker users compared with non-users (OR=0.94 95% CI 0.81, 1.09). Similar results were observed after adjustments for confounders, in analyses by beta-blocker frequency, duration, type and for all-cause mortality. Conclusions: Beta-blocker usage after diagnosis was not associated with cancer-specific or all-cause mortality in prostate cancer patients in this large UK study.
    Cancer epidemiology. 04/2014;
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    ABSTRACT: Recent observational studies indicate that post-diagnostic use of aspirin in breast cancer patients may protect against cancer progression perhaps by inhibiting cyclooxygenase-2 dependent mechanisms. Evidence also supports a crucial role for interactions between tumour cells and circulating platelets in cancer growth and dissemination, therefore, use of low-dose aspirin may reduce the risk of death from cancer in breast cancer patients. A cohort of newly diagnosed breast cancer patients (1998-2006) were identified in the UK Clinical Practice Research Datalink (and confirmed by cancer registry linkage). Cancer-specific deaths were identified up to 2011 from Office for National Statistics mortality data. A nested case-control analysis was conducted using conditional logistic regression to compare post-diagnostic aspirin exposure using General Practice prescription data in 1,435 cases (breast cancer deaths) with 5,697 controls (matched by age and year of diagnosis). After breast cancer diagnosis, 18.3% of cancer-specific deaths and 18.5% of matched controls received at least one prescription for low-dose aspirin, corresponding to an odds ratio (OR) of 0.98 (95% CI 0.83, 1.15). Adjustment for potential confounders (including stage and grade) had little impact on this estimate. No dose response relationship was observed when the number of tablets was investigated and no associations were seen when analyses were stratified by receipt of prescriptions for aspirin in the pre-diagnostic period, by stage at diagnosis or by receipt of prescriptions for hormone therapy. Overall, in this large population-based cohort of breast cancer patients, there was little evidence of an association between receipt of post-diagnostic prescriptions for low-dose aspirin and breast cancer-specific death. However, information was not available on medication compliance or over-the-counter use of aspirin, which may have contributed to the null findings.
    Breast cancer research: BCR 04/2014; 16(2):R34. · 5.87 Impact Factor
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    ABSTRACT: Background To investigate the association between post-diagnostic beta-blocker usage and risk of melanoma-specific mortality in a population-based cohort of malignant melanoma patients. Methods Incident malignant melanoma patients diagnosed between 1998 and 2010 were identified within the UK Clinical Practice Research Datalink and confirmed using cancer registry data. Malignant melanoma patients with a melanoma-specific death (cases) recorded by the Office of National Statistics were matched on year of diagnosis, age and sex to 4 malignant melanoma controls (who lived at least as long after diagnosis as their matched case). A nested case-control approach was used to investigate the association between post-diagnostic beta-blocker usage and melanoma-specific death and all-cause mortality. Conditional logistic regression was applied to generate odds ratios (OR) and 95% confidence intervals (CI) for beta-blocker use determined from GP prescribing. ResultsBeta-blocker medications were prescribed after malignant melanoma diagnosis to 20.2% of 242 patients who died from malignant melanoma (cases) and 20.3% of 886 matched controls. Consequently, there was no association between beta-blockers use post-diagnosis and cancer-specific death (OR 0.99, 95% CI 0.68-1.42), which did not markedly alter after adjustment for confounders including stage (OR 0.87, 95% CI 0.56-1.34). No significant associations were detected for individual beta-blocker types, by defined daily doses of use or for all-cause mortality. Conclusion Contrary to some previous studies, beta-blocker usage after malignant melanoma diagnosis was not associated with reduced risk of death from melanoma in this UK population-based study.This article is protected by copyright. All rights reserved.
    British Journal of Dermatology 03/2014; · 3.76 Impact Factor
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    ABSTRACT: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are commonly prescribed to the growing number of cancer patients (more than two million in the UK alone) often to treat hypertension. However, increased fatal cancer in ARB users in a randomized trial and increased breast cancer recurrence rates in ACEI users in a recent observational study have raised concerns about their safety in cancer patients. We investigated whether ACEI or ARB use after breast, colorectal or prostate cancer diagnosis was associated with increased risk of cancer-specific mortality. Population-based cohorts of 9,814 breast, 4,762 colorectal and 6,339 prostate cancer patients newly diagnosed from 1998 to 2006 were identified in the UK Clinical Practice Research Datalink and confirmed by cancer registry linkage. Cancer-specific and all-cause mortality were identified from Office of National Statistics mortality data in 2011 (allowing up to 13 years of follow-up). A nested case-control analysis was conducted to compare ACEI/ARB use (from general practitioner prescription records) in cancer patients dying from cancer with up to five controls (not dying from cancer). Conditional logistic regression estimated the risk of cancer-specific, and all-cause, death in ACEI/ARB users compared with non-users. The main analysis included 1,435 breast, 1,511 colorectal and 1,184 prostate cancer-specific deaths (and 7,106 breast, 7,291 colorectal and 5,849 prostate cancer controls). There was no increase in cancer-specific mortality in patients using ARBs after diagnosis of breast (adjusted odds ratio (OR) = 1.06 95% confidence interval (CI) 0.84, 1.35), colorectal (adjusted OR = 0.82 95% CI 0.64, 1.07) or prostate cancer (adjusted OR = 0.79 95% CI 0.61, 1.03). There was also no evidence of increases in cancer-specific mortality with ACEI use for breast (adjusted OR = 1.06 95% CI 0.89, 1.27), colorectal (adjusted OR = 0.78 95% CI 0.66, 0.92) or prostate cancer (adjusted OR = 0.78 95% CI 0.66, 0.92). Overall, we found no evidence of increased risks of cancer-specific mortality in breast, colorectal or prostate cancer patients who used ACEI or ARBs after diagnosis. These results provide some reassurance that these medications are safe in patients diagnosed with these cancers.
    BMC Medicine 02/2014; 12(1):28. · 6.68 Impact Factor
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    ABSTRACT: Aspirin use is associated with reduced risk of, and death from, prostate cancer. Our aim was to determine whether low-dose aspirin use after a prostate cancer diagnosis was associated with reduced prostate cancer-specific mortality. A cohort of newly diagnosed prostate cancer patients (1998-2006) was identified in the UK Clinical Practice Research Datalink (confirmed by cancer registry linkage). A nested case-control analysis was conducted using conditional logistic regression to compare aspirin usage in cases (prostate cancer deaths) with up to three controls (matched by age and year of diagnosis). Post-diagnostic low-dose aspirin use was identified in 52 % of 1,184 prostate cancer-specific deaths and 39 % of 3,531 matched controls (unadjusted OR 1.51, 95 % CI 1.19, 1.90; p < 0.001). After adjustment for confounders including treatment and comorbidities, this association was attenuated (adjusted OR 1.02 95 % CI 0.78, 1.34; p = 0.86). Adjustment for estrogen therapy accounted for the majority of this attenuation. There was also no evidence of dose-response association after adjustments. Compared with no use, patients with 1-11 prescriptions and 12 or more prescriptions had adjusted ORs of 1.07 (95 % CI 0.78, 1.47; p = 0.66) and 0.97 (95 % CI 0.69, 1.37; p = 0.88), respectively. There was no evidence of a protective association between low-dose aspirin use in the year prior to diagnosis and prostate cancer-specific mortality (adjusted OR 1.04 95 % CI 0.89, 1.22; p = 0.60). We found no evidence of an association between low-dose aspirin use before or after diagnosis and risk of prostate cancer-specific mortality, after potential confounders were accounted for, in UK prostate cancer patients.
    Cancer Causes and Control 12/2013; · 3.20 Impact Factor
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    ABSTRACT: To investigate the association between post-diagnostic beta-blocker usage and risk of cancer-specific mortality in a large population-based cohort of female breast cancer patients. A nested case-control study was conducted within a cohort of breast cancer patients identified from cancer registries in England(using the National Cancer Data repository) and diagnosed between 1998 and 2007. Patients who had a breast cancer-specific death(ascertained from Office of National Statistics death registration data) were each matched to four alive controls by year and age at diagnosis. Prescription data for these patients were available through the Clinical Practice Research Datalink. Conditional logistic regression models were used to investigate the association between breast cancer-specific death and beta-blocker usage. Post-diagnostic use of beta-blockers was identified in 18.9% of 1435 breast cancer-specific deaths and 19.4% of their 5697 matched controls,indicating little evidence of association between beta-blocker use and breast cancer-specific mortality [odds ratio (OR) = 0.97,95% confidence interval (CI) 0.83, 1.13]. There was also little evidence of an association when analyses were restricted to cardio non-selective beta-blockers (OR = 0.90, 95% CI 0.69, 1.17). Similar results were observed in analyses of drug dosage frequency and duration, and beta-blocker type. In this large UK population-based cohort of breast cancer patients,there was little evidence of an association between post-diagnostic beta-blocker usage and breast cancer progression. Further studies which include information on tumour receptor status are warranted to determine whether response to beta-blockers varies by tumour subtypes.
    International Journal of Epidemiology 12/2013; 42(6):1852-61. · 6.98 Impact Factor
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    ABSTRACT: Individuals who began taking low-dose aspirin before they were diagnosed with colorectal cancer were reported to have longer survival times than patients who did not take this drug. We investigated survival times of patients who begin taking low-dose aspirin after a diagnosis of colorectal cancer in a large population-based cohort study. We performed a nested case-control analysis using a cohort of 4794 patients diagnosed with colorectal cancer from 1998 through 2007, identified from the UK Clinical Practice Research Datalink and confirmed by cancer registries. There were 1559 colorectal cancer-specific deaths, recorded by the Office of National Statistics; these were each matched with up to 5 risk-set controls. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI), based on practitioner-recorded aspirin usage. Overall, low-dose aspirin use after a diagnosis of colorectal cancer was not associated with colorectal cancer-specific mortality (adjusted OR=1.06; 95% CI, 0.92-1.24) or all-cause mortality (adjusted OR=1.06; 95% CI, 0.94-1.19). A dose-response association was not apparent; for example, low-dose aspirin use for more than 1 y after diagnosis was not associated with colorectal cancer-specific mortality (adjusted OR=0.98; 95% CI, 0.82-1.19). Nor was there an association between low-dose aspirin usage and colon cancer-specific mortality (adjusted OR=1.02; 95% CI, 0.83-1.25) or rectal cancer-specific mortality (adjusted OR=1.10; 95% CI, 0.88-1.38). In a large population-based cohort, low-dose aspirin usage after diagnosis of colorectal cancer did not increase survival time.
    Gastroenterology 11/2013; · 12.82 Impact Factor
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    ABSTRACT: To evaluate a psychoeducational intervention for patients with advanced cancer who have cachexia and their lay carers. Cachexia is a frequent and devastating syndrome of advanced cancer. It has an impact on patients biologically, psychologically and socially and has profound impact on their lay carers. Prior research has predominately focused on the biological components of cachexia and associated potential treatment modalities. At present, there is no standardized supportive healthcare intervention in current practice that targets the psychosocial impact of this syndrome. A pragmatic multicentre randomized controlled trial. Patient/carer dyads (n = 200) will be recruited into a randomized controlled trial of a DVD intervention for cachexia management. The sample will be recruited from two urban hospices in the UK. The primary outcome measure will be the General Health Questionnaire-12. Additional questionnaires focusing on distress, readiness to give care and coping skills will be used as secondary outcome measures. In addition, lay carers in the intervention group will be asked to participate in semi-structured interviews following the death of their loved one. Both Office for Research Ethics Committee approval and local governance approval at both hospices have been obtained as of February 2013. This is the first time that a psychoeducational DVD has been tested in a randomized controlled trial in this population. Dissemination of findings will make a significant contribution to international knowledge and understanding in this area. Findings will inform education, practice and policy.
    Journal of Advanced Nursing 10/2013; · 1.53 Impact Factor
  • E Morgan, C C Patterson, C R Cardwell
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    ABSTRACT: To investigate whether young people with Type 1 diabetes have an increased rate of depression and antidepressant use and whether their risk varies by age group, time from diabetes diagnosis, calendar period of diagnosis or complications status. A cohort of incident cases of patients with Type 1 diabetes diagnosed before 35 years of age (n = 5548) was identified within the Clinical Practice Research Datalink and individually age and sex matched with up to two control subjects without diabetes (n = 10 657). Patients with depression were identified through general practice-recorded depression codes and antidepressant prescriptions. Cox regression models gave hazard ratios for depression in people with Type 1 diabetes compared with control subjects. People with Type 1 diabetes were twice as likely to have a record of antidepressant use and general practice-diagnosed depression as their matched control subjects (hazard ratio 2.08, 95% CI 1.73-2.50, P < 0.001). These associations varied by time from diagnosis, with marked increases observed within the first 5 years of diagnosis (hazard ratio 2.14, 95% CI 1.51-3.03, P < 0.001), and by age at diabetes diagnosis, with excesses noted even in the 10- to 19-year age group (hazard ratio 1.45, 95% CI 1.06-1.98, P = 0.02). This population-based study shows that people with Type 1 diabetes have higher rates of general practice-recorded depression and antidepressant use. The excess is present within 5 years of diabetes diagnosis, suggesting psychological input for patients is warranted in the early years of their condition. This article is protected by copyright. All rights reserved.
    Diabetic Medicine 09/2013; · 3.24 Impact Factor
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    ABSTRACT: Epidemiological and laboratory studies suggest that β-blockers may reduce cancer progression in various cancer sites. The aim of this study was to conduct the first epidemiological investigation of the effect of post-diagnostic β-blocker usage on colorectal cancer-specific mortality in a large population-based colorectal cancer patient cohort.Patients and methods: A nested case-control analysis was conducted within a cohort of 4794 colorectal cancer patients diagnosed between 1998 and 2007. Patients were identified from the UK Clinical Practice Research Datalink and confirmed using cancer registry data. Patients with a colorectal cancer- specific death (data from the Office of National Statistics death registration system) were matched to five controls. Conditional logistic regression was applied to calculate odds ratios (OR) and 95% confidence intervals (95% CIs) according to β-blocker usage (data from GP-prescribing records). Post-diagnostic β-blocker use was identified in 21.4% of 1559 colorectal cancer-specific deaths and 23.7% of their 7531 matched controls, with little evidence of an association (OR = 0.89 95% CI 0.78-1.02). Similar associations were found when analysing drug frequency, β-blocker type or specific drugs such as propranolol. There was some evidence of a weak reduction in all-cause mortality in β-blocker users (adjusted OR = 0.88; 95% CI 0.77-1.00; P = 0.04) which was in part due to the marked effect of atenolol on cardiovascular mortality (adjusted OR = 0.62; 95% CI 0.40-0.97; P = 0.04). In this novel, large UK population-based cohort of colorectal cancer patients, there was no evidence of an association between post-diagnostic β-blocker use and colorectal cancer-specific mortality. NCT00888797.
    Annals of Oncology 09/2013; · 7.38 Impact Factor
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    ABSTRACT: We investigated the prevalence of chronic kidney disease and attainment of therapeutic targets for HbA1c and blood pressure in a large UK-based diabetes population. The UK National Diabetes Audit provided data from 1 January 2007 to 31 March 2008. Inclusion criteria were a documented urinary albumin:creatinine ratio and serum creatinine. Patients were stratified according to chronic kidney disease stage and albuminuria status. Chronic kidney disease was defined as an estimated glomerular filtration rate < 60 ml min(-1) 1.73 m(-2) , albuminuria or both. The proportions of patients achieving nationally defined glycaemic and systolic blood pressure targets were determined. The cohort comprised 1 423 669 patients, of whom 868 616 (61%) met inclusion criteria. Of the patients analysed, 92.2% had Type 2 diabetes. A higher proportion of people with Type 2 diabetes (42.3%) had renal dysfunction compared with those with Type 1 diabetes (32.4%). Achievement of systolic blood pressure and HbA1c targets was poor. Among people with Type 1 diabetes, 67.8% failed to achieve an HbA1c < 58 mmol/mol (7.5%). Of all people with diabetes, 37.8% failed to achieve a systolic blood pressure < 140 mmHg. Blood pressure control was poor in advanced chronic kidney disease. For example, mean (standard deviation) systolic blood pressure rose from 128.6 (15.4) mmHg among people with Type 1 diabetes and normal renal function to 141.0 (23.6) mmHg in those with chronic kidney disease stage 5 and macroalbuminuria. The high prevalence of chronic kidney disease and poor attainment of treatment targets highlights a large subset of the diabetes population at increased risk of cardiovascular mortality or progressive kidney disease.
    Diabetic Medicine 09/2013; · 3.24 Impact Factor
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    ABSTRACT: The aetiology of primary brain tumours is largely unknown; the role of non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin use and glioma risk has been inconclusive, but few population-based studies with reliable prescribing data have been conducted, and the association with meningioma risk has yet to be assessed. The UK Clinical Practice Research Datalink was used to assess the association between aspirin and non-aspirin NSAID use and primary brain tumour risk using a nested case-control study design. Conditional logistic regression analysis was performed on 5,052 brain tumour patients aged 16 years and over, diagnosed between 1987 and 2009 and 42,678 controls matched on year of birth, gender and general practice, adjusting for history of allergy and hormone replacement therapy use in the glioma and meningioma models, respectively. In conditional logistic regression analysis, excluding drug use in the year preceding the index date, there was no association with non-aspirin NSAID use (OR 0.96, 95 % CI 0.81-1.13) or glioma risk comparing the highest category of daily defined dose to non-users; however, non-aspirin NSAID use was positively associated with meningioma risk (OR 1.35, 95 % CI 1.06-1.71). No association was seen with high- or low-dose aspirin use irrespective of histology. This large nested case-control study finds no association between aspirin or non-aspirin NSAID use and risk of glioma but a slight increased risk with non-aspirin NSAIDs and meningioma.
    Cancer Causes and Control 08/2013; · 3.20 Impact Factor
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    ABSTRACT: Background Mechanical ventilation is a critical component of paediatric intensive care therapy. It is indicated when the patient’s spontaneous ventilation is inadequate to sustain life. Weaning is the gradual reduction of ventilatory support and the transfer of respiratory control back to the patient. Weaning may represent a large proportion of the ventilatory period. Prolonged ventilation is associated with significant morbidity, hospital cost, psychosocial and physical risks to the child and even death. Timely and effective weaning may reduce the duration of mechanical ventilation and may reduce the morbidity and mortality associated with prolonged ventilation. However, no consensus has been reached on criteria that can be used to identify when patients are ready to wean or the best way to achieve it. Objectives To assess the effects of weaning by protocol on invasively ventilated critically ill children. To compare the total duration of invasive mechanical ventilation of critically ill children who are weaned using protocols versus those weaned through usual (non-protocolized) practice. To ascertain any differences between protocolized weaning and usual care in terms of mortality, adverse events, intensive care unit length of stay and quality of life. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library, Issue 10, 2012), MEDLINE (1966 to October 2012), EMBASE (1988 to October 2012), CINAHL (1982 to October 2012), ISI Web of Science and LILACS. We identified unpublished data in the Web of Science (1990 to October 2012), ISI Conference Proceedings (1990 to October 2012) and Cambridge Scientific Abstracts (earliest to October 2012). We contacted first authors of studies included in the review to obtain further information on unpublished studies or work in progress. We searched reference lists of all identified studies and review papers for further relevant studies. We applied no language or publication restrictions. Selection criteria We included randomized controlled trials comparing protocolized weaning (professional-led or computer-driven) versus non-protocolized weaning practice conducted in children older than 28 days and younger than 18 years. Data collection and analysis Two review authors independently scanned titles and abstracts identified by electronic searching. Three review authors retrieved and evaluated full-text versions of potentially relevant studies, independently extracted data and assessed risk of bias. Main results We included three trials at low risk of bias with 321 children in the analysis. Protocolized weaning significantly reduced total ventilation time in the largest trial (260 children) by a mean of 32 hours (95% confidence interval (CI) 8 to 56; P = 0.01). Two other trials (30 and 31 children, respectively) reported non-significant reductions with a mean difference of -88 hours (95% CI -228 to 52; P = 0.2) and -24 hours (95% CI -10 to 58; P = 0.06). Protocolized weaning significantly reduced weaning time in these two smaller trials for a mean reduction of 106 hours (95% CI 28 to 184; P = 0.007) and 21 hours (95% CI 9 to 32; P < 0.001). These studies reported no significant effects for duration of mechanical ventilation before weaning, paediatric intensive care unit (PICU) and hospital length of stay, PICU mortality or adverse events. Authors' conclusions Limited evidence suggests that weaning protocols reduce the duration of mechanical ventilation, but evidence is inadequate to show whether the achievement of shorter ventilation by protocolized weaning causes children benefit or harm.
    Cochrane database of systematic reviews (Online) 07/2013; · 5.70 Impact Factor
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    ABSTRACT: Chronic Pseudomonas aeruginosa pulmonary infection is associated with a decline in lung function and reduced survival in people with Cystic Fibrosis (CF). Damaging inflammatory and immunological mediators released in the lungs can be used as markers of chronic infection, inflammation and lung tissue damage. Clinical samples were collected from CF patients and healthy controls. Serum IgG and IgA anti-Pseudomonas antibodies, sputum IL-8 and TNFα, plasma IL-6 and urine TNFr1 were measured by ELISA. Sputum neutrophil elastase (NE), cathepsin S and cathepsin B were measured by spectrophotometric and fluorogenic assays. The relationship between IgG and IgA, inflammatory mediators and long-term survival was determined. IgG and IL-6 positively correlated with mortality. However, multivariate analysis demonstrated that after adjusting for FEV1, IgG was not independently related to mortality. A relationship was observed between IgG and IL-6, TNFα, TNFr1 and between IgA and IL8, cathepsin S and cathepsin B. These data indicate that biomarkers of inflammation are not independent predictors of survival in people with CF.
    Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 07/2013; · 3.19 Impact Factor
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    ABSTRACT: Dietary fiber has several anticarcinogenic effects and is thought to be protective against esophageal cancer. The aim of this systematic review was to quantify the association between dietary fiber and the risk of esophageal cancer by investigating histological subtypes of esophageal cancer and the stage at which fiber may influence the carcinogenic pathway. Systematic search strategies were used to identify relevant studies, and adjusted odds ratios (ORs) were combined using random-effects meta-analyses to assess the risk of cancer when comparing extreme categories of fiber intake. Ten relevant case-control studies were identified within the timeframe searched. Pooled estimates from eight studies of esophageal adenocarcinoma revealed a significant inverse association with the highest fiber intakes (OR 0.66; 95% confidence interval [CI] 0.44-0.98). Two studies also identified protective effects of dietary fiber against Barrett's esophagus. Similar, though nonsignificant, associations were observed when results from five studies of fiber intake and risk of squamous cell carcinoma were combined (OR 0.61; 95%CI 0.31-1.20). Dietary fiber is associated with protective effects against esophageal carcinogenesis, most notably esophageal adenocarcinoma. Potential methods of action include modification of gastroesophageal reflux and/or weight control.
    Nutrition Reviews 07/2013; 71(7):474-82. · 4.60 Impact Factor
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    ABSTRACT: Background:Studies have examined whether tumour expression of PTGS2 (also known as cyclooxygenase-2), an enzyme inhibited by non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, is associated with prognosis in colorectal cancer patients. However, results to date have been mixed. Methods:Using terms for PTGS2 and colorectal cancer, the Medline, Embase and Web of Science databases were systematically searched for studies published, in any language, until December 2011. Random effects meta-analyses were used to calculate pooled Hazard Ratios (HR) (95%Confidence intervals (CI)) for the association between PTGS2 expression and tumour recurrence, colorectal cancer-specific survival and overall survival. Results:In total, 29 studies, which had prognostic data on 5648 patients, met the inclusion criteria. PTGS2 positive patients were at an increased risk of tumour recurrence (n=9 studies; HR 2.79; 95%CI 1.76-4.41, p<0.001), and had poorer colorectal cancer-specific survival (n=7; HR 1.36; 95%CI 1.02-1.82, p=0.04). However, there was funnel plot asymmetry, possibly due to publication bias, for the association with cancer-specific survival but less so for recurrence. PTGS2 expression was not associated with overall survival (n= 16; pooled unadjusted HR 1.30; 95%CI 0.94-1.79, p=0.11) and (n=9; pooled adjusted HR=1.02; 95%CI 0.72-1.45, p=0.91). Conclusions:PTGS2 expression was associated with an increased risk of tumour recurrence and poorer colorectal cancer-specific survival but not overall survival amongst colorectal cancer patients. However, confounding by tumour characteristics, such as tumour stage, seems likely. Impact:There is insufficient evidence to recommend PTGS2 expression as a prognostic marker in colorectal cancer patients. Further studies providing adjusted results are required.
    Cancer Epidemiology Biomarkers &amp Prevention 06/2013; · 4.56 Impact Factor
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    ABSTRACT: BACKGROUND: Automated closed loop systems may improve adaptation of the mechanical support to a patient's ventilatory needs and facilitate systematic and early recognition of their ability to breathe spontaneously and the potential for discontinuation of ventilation. OBJECTIVES: To compare the duration of weaning from mechanical ventilation for critically ill ventilated adults and children when managed with automated closed loop systems versus non-automated strategies. Secondary objectives were to determine differences in duration of ventilation, intensive care unit (ICU) and hospital length of stay (LOS), mortality, and adverse events. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2); MEDLINE (OvidSP) (1948 to August 2011); EMBASE (OvidSP) (1980 to August 2011); CINAHL (EBSCOhost) (1982 to August 2011); and the Latin American and Caribbean Health Sciences Literature (LILACS). In addition we received and reviewed auto-alerts for our search strategy in MEDLINE, EMBASE, and CINAHL up to August 2012. Relevant published reviews were sought using the Database of Abstracts of Reviews of Effects (DARE) and the Health Technology Assessment Database (HTA Database). We also searched the Web of Science Proceedings; conference proceedings; trial registration websites; and reference lists of relevant articles. SELECTION CRITERIA: We included randomized controlled trials comparing automated closed loop ventilator applications to non-automated weaning strategies including non-protocolized usual care and protocolized weaning in patients over four weeks of age receiving invasive mechanical ventilation in an intensive care unit (ICU). DATA COLLECTION AND ANALYSIS: Two authors independently extracted study data and assessed risk of bias. We combined data into forest plots using random-effects modelling. Subgroup and sensitivity analyses were conducted according to a priori criteria. MAIN RESULTS: Pooled data from 15 eligible trials (14 adult, one paediatric) totalling 1173 participants (1143 adults, 30 children) indicated that automated closed loop systems reduced the geometric mean duration of weaning by 32% (95% CI 19% to 46%, P = 0.002), however heterogeneity was substantial (I(2) = 89%, P < 0.00001). Reduced weaning duration was found with mixed or medical ICU populations (43%, 95% CI 8% to 65%, P = 0.02) and Smartcare/PS™ (31%, 95% CI 7% to 49%, P = 0.02) but not in surgical populations or using other systems. Automated closed loop systems reduced the duration of ventilation (17%, 95% CI 8% to 26%) and ICU length of stay (LOS) (11%, 95% CI 0% to 21%). There was no difference in mortality rates or hospital LOS. Overall the quality of evidence was high with the majority of trials rated as low risk. AUTHORS' CONCLUSIONS: Automated closed loop systems may result in reduced duration of weaning, ventilation, and ICU stay. Reductions are more likely to occur in mixed or medical ICU populations. Due to the lack of, or limited, evidence on automated systems other than Smartcare/PS™ and Adaptive Support Ventilation no conclusions can be drawn regarding their influence on these outcomes. Due to substantial heterogeneity in trials there is a need for an adequately powered, high quality, multi-centre randomized controlled trial in adults that excludes 'simple to wean' patients. There is a pressing need for further technological development and research in the paediatric population.
    Cochrane database of systematic reviews (Online) 06/2013; 6:CD009235. · 5.70 Impact Factor
  • Chris R Cardwell, Samy Suissa, Liam J Murray
    European Urology 04/2013; · 10.48 Impact Factor
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    ABSTRACT: RATIONALE: Characterization of bacterial populations in infectious respiratory diseases will provide improved understanding of the relationship between the lung microbiota, disease pathogenesis and treatment outcomes. OBJECTIVES: To comprehensively define lung microbiota composition during stable disease and exacerbation in bronchiectasis patients. METHODS: Sputum was collected from patients when clinically stable and before and after completion of antibiotic treatment of exacerbations. Bacterial abundance and community composition were analyzed using anaerobic culture and 16S rDNA pyrosequencing. MEASUREMENTS AND MAIN RESULTS: In clinically stable patients, aerobic and anaerobic bacteria were detected in 40/40 (100%) and 33/40 (83%) sputum samples, respectively. The dominant organisms cultured were P. aeruginosa (n=10 patients), H. influenzae (n=12), Prevotella (n=18) and Veillonella (n=13). Pyrosequencing generated over 150,000 sequences, representing 113 distinct microbial taxa; the majority of observed community richness resulted from taxa present in low abundance with similar patterns of phyla distribution in clinically stable patients and patients at the onset of exacerbation. Following treatment of exacerbation, there was no change in total (p=0.925), aerobic (p=0.917) or anaerobic (p=0.683) load and only a limited shift in community composition. Agreement for detection of bacteria by culture and pyrosequencing was good for aerobic bacteria such as P. aeruginosa (kappa=0.84) but poorer for other genera including anaerobes. Lack of agreement was largely due to bacteria been detected by pyrosequencing but not by culture. CONCLUSIONS: A complex microbiota is present in the lungs of bronchiectasis patients which remains stable through treatment of exacerbations suggesting that changes in microbiota composition do not account for exacerbations.
    American Journal of Respiratory and Critical Care Medicine 01/2013; · 11.04 Impact Factor
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    ABSTRACT: Background:Research examining the relationship between adiponectin (AN) isoforms, body weight and cardiovascular (CV) risk factors is limited, particularly in younger populations.Objectives:To investigate the inter-relationships between AN isoforms and CV risk factors, and their dependence on body weight status, in adolescents.Design:Blood samples from 92 obese, 92 overweight and 92 normal weight age- and sex-matched adolescents were analysed for traditional cardiovascular disease (CVD) risk biomarkers and also total, high molecular weight (HMW), medium and low molecular weight (LMW) AN.Results:A significant inverse association was observed between total and HMW AN and waist-hip ratio (P=0.015, P=0.006, respectively), triglycerides (P=0.003, P=0.003, respectively) and systolic blood pressure (P=0.012, P=0.024, respectively) and a significant positive association with high-density lipoprotein (P<0.001, P<0.001, respectively) in multi-adjusted analyses. There was no evidence of a relationship between multimeric AN and high-sensitivity C-reactive protein. There was also little evidence of a relationship between LMW AN and CVD risk factors. There was a strong, body mass index (BMI)-independent, association between AN, CVD biomarkers and the hypertriglyceridemic waist phenotype.Conclusion:Prominent, BMI-independent associations between total and HMW AN, but not LMW AN, and CVD risk factors were already evident in this young population. This research in adolescents supports the contention that AN subfractions may have different biological actions. These associations in apparently healthy adolescents suggest an important role for AN and its subfractions in the pathogenesis of metabolic syndrome traits and indicate that the potential for total or HMW AN to act as early universal biomarkers of CV risk warrants further study.International Journal of Obesity advance online publication, 15 January 2013; doi:10.1038/ijo.2012.214.
    International journal of obesity (2005) 01/2013; · 5.22 Impact Factor