[Show abstract][Hide abstract] ABSTRACT: Automated weaning systems may improve adaptation of mechanical support for a patient's ventilatory needs and facilitate systematic and early recognition of their ability to breathe spontaneously and the potential for discontinuation of ventilation. Our objective was to compare mechanical ventilator weaning duration for critically ill adults and children when managed with automated 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.
Electronic databases were searched to 30 September 2013 without language restrictions. We also searched conference proceedings; trial registration websites; and article reference lists. Two authors independently extracted data and assessed risk of bias. We combined data using random-effects modelling.
We identified 21 eligible trials totalling 1,676 participants. Pooled data from 16 trials indicated that automated systems reduced the geometric mean weaning duration by 30% (95% confidence interval (CI) 13% to 45%), with substantial heterogeneity (I(2) = 87%, P <0.00001). Reduced weaning duration was found with mixed or medical ICU populations (42%, 95% CI 10% to 63%) and Smartcare/PS™ (28%, 95% CI 7% to 49%) but not with surgical populations or using other systems. Automated systems reduced ventilation duration with no heterogeneity (10%, 95% CI 3% to 16%) and ICU LOS (8%, 95% CI 0% to 15%). There was no strong evidence of effect on mortality, hospital LOS, reintubation, self-extubation and non-invasive ventilation following extubation. Automated systems reduced prolonged mechanical ventilation and tracheostomy. Overall quality of evidence was high.
Automated systems may reduce weaning and ventilation duration and ICU stay. Due to substantial trial heterogeneity an adequately powered, high quality, multi-centre randomized controlled trial is needed.
Critical Care 12/2015; 19(1). DOI:10.1186/s13054-015-0755-6 · 4.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Digoxin has been shown to have an estrogenic effect and is associated with increased risk of gynecomastia and estrogen-sensitive cancers such as breast and uterus cancer. These findings, particularly recent observations of increased breast cancer risk, raise questions about the safety of digoxin use in breast cancer patients. Therefore, we investigated whether digoxin use after breast cancer diagnosis increased the risk of breast cancer-specific mortality in breast cancer patients. A cohort of 17,842 breast cancer patients newly diagnosed from 1998 to 2009 was identified from English cancer registries (from the National Cancer Data Repository). This cohort was 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 breast cancer-specific deaths). Using time-dependent Cox regression models, unadjusted and adjusted hazard ratios (HR) and 95 % confidence intervals (CIs) were calculated for the association between post-diagnostic exposure to digoxin and breast cancer-specific and all-cause mortality. In 17,842 breast cancer patients, there were 2219 breast cancer-specific deaths. Digoxin users appeared to have increased breast cancer-specific mortality compared with non-users (HR 1.73; 95 % CI 1.39–2.15) but this association was entirely attenuated after adjustment for potential confounders (adjusted HR 0.91; 95 % CI 0.72–1.14). In this large population-based breast cancer cohort study, there was little evidence of an increase in breast cancer-specific mortality with digoxin use after diagnosis. These results provide some reassurance that digoxin use is safe in breast cancer patients.
Breast Cancer Research and Treatment 09/2015; 151(3):661-669. DOI:10.1158/1055-9965.EPI-15-0694 · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Preclinical evidence suggests that metformin could delay cancer progression. Previous epidemiological studies however havebeen limited by small sample sizes and certain time-related biases. This study aimed to investigate whether colorectal cancerpatients with type 2 diabetes who were exposed to metformin had reduced cancer-specific mortality. We conducted a retro-spective cohort study of 1,197 colorectal cancer patients newly diagnosed from 1998 to 2009 (identified from English cancerregistries) with type 2 diabetes (based upon Clinical Practice Research Datalink, CPRD, prescription and diagnosis records). Inthis cohort 382 colorectal cancer-specific deaths occurred up to 2012 from the Office of National Statistics (ONS) mortalitydata. Metformin use was identified from CPRD prescription records. Using time-dependent Cox regression models, unadjustedand adjusted hazard ratios (HR) and 95% CIs were calculated for the association between post-diagnostic exposure to metfor-min and colorectal cancer-specific mortality. Overall, there was no evidence of an association between metformin use andcancer-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 dura-tion of use and for all-cause mortality. This population-based study, the largest to date, does not support a protective associa-tion between metformin and survival in colorectal cancer patients.
International Journal of Cancer 08/2015; DOI:10.1002/ijc.29720 · 5.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine whether combining potential biomarkers of fruit and vegetables is better at predicting FV intake within FV intervention studies than single biomarkers.
Data from a tightly controlled randomised FV intervention study (BIOFAV; all food provided and two meals/day on weekdays consumed under supervision) were used. A total of 30 participants were randomised to either 2, 5 or 8 portions FV/day for 4 weeks, and blood samples were collected at baseline and 4 weeks for plasma vitamin C and serum carotenoid analysis. The combined biomarker approach was also tested in three further FV intervention studies conducted by the same research team, with less strict dietary control (FV provided and no supervised meals).
The combined model containing all carotenoids and vitamin C was a better fit than either the vitamin C only (P < 0.001) model or the lutein only (P = 0.006) model in the BIOFAV study. The C-statistic was slightly lower in the lutein only model (0.85) and in the model based upon factor analysis (0.88), and much lower in the vitamin C model (0.68) compared with the full model (0.95). Results for the other studies were similar, although the differences between the models were less marked.
Although there was some variation between studies, which may relate to the level of dietary control or participant characteristics, a combined biomarker approach to assess overall FV consumption may more accurately predict FV intake within intervention studies than the use of a single biomarker. The generalisability of these findings to other populations and study designs remains to be tested. Clinical trial Registration Number NCT01591057 ( www.clinicaltrials.gov ).
European Journal of Nutrition 06/2015; DOI:10.1007/s00394-015-0953-7 · 3.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We conducted the first study to investigate post-diagnostic oral bisphosphonates use and colorectal cancer-specific mortality.
Colorectal cancer patients were identified from the National Cancer Data Repository (1998-2007) and linked to the UK Clinical Practice Research Datalink, providing prescription records, and Office of National Statistics mortality data. Time-dependent Cox regression models investigated colorectal cancer-specific mortality in post-diagnostic bisphosphonate users.
Overall, in 4791 colorectal cancer patients, there was no evidence of an association between bisphosphonate use and colorectal cancer-specific mortality (adjusted hazard ratio=1.11; 95% confidence interval 0.80, 1.54) or with drug frequency or type.
In this novel population-based cohort study, post-diagnostic bisphosphonate use was not associated with longer rates of colorectal cancer survival.British Journal of Cancer advance online publication, 19 May 2015; doi:10.1038/bjc.2015.152 www.bjcancer.com.
British Journal of Cancer 05/2015; 113(1). DOI:10.1038/bjc.2015.152 · 4.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Digoxin has been shown to have an estrogenic effect and is associated with increased risk of gynecomastia and estrogen-sensitive cancers such as breast and uterus cancer. These findings, particularly recent observations of increased breast cancer risk, raise questions about the safety of digoxin use in breast cancer patients. Therefore, we investigated whether digoxin use after breast cancer diagnosis increased the risk of breast cancer-specific mortality in breast cancer patients. A cohort of 17,842 breast cancer patients newly diagnosed from 1998 to 2009 was identified from English cancer registries (from the National Cancer Data Repository). This cohort was 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 breast cancer-specific deaths). Using time-dependent Cox regression models, unadjusted and adjusted hazard ratios (HR) and 95 % confidence intervals (CIs) were calculated for the association between post-diagnostic exposure to digoxin and breast cancer-specific and all-cause mortality. In 17,842 breast cancer patients, there were 2219 breast cancer-specific deaths. Digoxin users appeared to have increased breast cancer-specific mortality compared with non-users (HR 1.73; 95 % CI 1.39-2.15) but this association was entirely attenuated after adjustment for potential confounders (adjusted HR 0.91; 95 % CI 0.72-1.14). In this large population-based breast cancer cohort study, there was little evidence of an increase in breast cancer-specific mortality with digoxin use after diagnosis. These results provide some reassurance that digoxin use is safe in breast cancer patients.
[Show abstract][Hide abstract] ABSTRACT: Introduction: Cerebral small-vessel disease has been implicated in the development of Alzheimer's disease (AD). The retinal microvasculature enables the noninvasive visualization and evaluation of the systemic microcirculation. We evaluated retinal microvascular parameters in a case-control study of AD patients and cognitively normal controls. Methods: Retinal images were computationally analyzed and quantitative retinal parameters (caliber, fractal dimension, tortuosity, and bifurcation) measured. Regression models were used to compute odds ratios (OR) and confidence intervals (CI) for AD with adjustment for confounders. Results: Retinal images were available in 213 AD participants and 294 cognitively normal controls. Persons with lower venular fractal dimension (OR per standard deviation [SD] increase, 0.77 [CI: 0.62-0.97]) and lower arteriolar tortuosity (OR per SD increase, 0.78 [CI: 0.63-0.97]) were more likely to have AD after appropriate adjustment. Discussion: Patients with AD have a sparser retinal microvascular network and retinal microvascular variation may represent similar pathophysiological events within the cerebral microvasculature of patients with AD.
[Show abstract][Hide abstract] ABSTRACT: This study assessed the association between glucose-lowering drug (GLD) use, including metformin, sulphonylurea derivatives and insulin, after breast cancer diagnosis and breast cancer-specific and all-cause mortality. 1763 breast cancer patients, diagnosed between 1998 and 2010, with type 2 diabetes were included. Cancer information was retrieved from English cancer registries, prescription data from the UK Clinical Practice Research Datalink and mortality data from the Office of National Statistics (up to January 2012). Time-varying Cox regression models were used to calculate HRs and 95 % CIs for the association between GLD use and breast cancer-specific and all-cause mortality. In 1057 patients with diabetes before breast cancer, there was some evidence that breast cancer-specific mortality decreased with each year of metformin use (adjusted HR 0.88; 95 % CI 0.75-1.04), with a strong association seen with over 2 years of use (adjusted HR 0.47; 95 % CI 0.26-0.82). Sulphonylurea derivative use for less than 2 years was associated with increased breast cancer-specific mortality (adjusted HR 1.70; 95 % CI 1.18-2.46), but longer use was not (adjusted HR 0.94; 95 % CI 0.54-1.66). In 706 patients who developed diabetes after breast cancer, similar patterns were seen for metformin, but sulphonylurea derivative use was strongly associated with cancer-specific mortality (adjusted HR 3.64; 95 % CI 2.16-6.16), with similar estimates for short- and long-term users. This study provides some support for an inverse association between, mainly long-term, metformin use and (breast cancer-specific) mortality. In addition, sulphonylurea derivative use was associated with increased breast cancer-specific mortality, but this should be interpreted cautiously, as it could reflect selective prescribing in advanced cancer patients.
Breast Cancer Research and Treatment 03/2015; 150(2). DOI:10.1007/s10549-015-3331-5 · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: Pre-clinical studies suggest that oral anticoagulant agents, such as warfarin, may inhibit metastases and potentially prolong survival in cancer patients. However, few population-based studies have examined the association between warfarin use and cancer-specific mortality.
Using prescribing, cause of death, and cancer registration data from the UK Clinical Practice Research Datalink, four population-based cohorts were constructed, comprising breast, colorectal, lung, and prostate cancer patients diagnosed between 1 January 1998, and the 31 December 2010. Comparing pre-diagnostic warfarin users to non-users, multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for cancer-specific mortality.
Overall, 16,525 breast, 12,902 colorectal, 12,296 lung, and 12,772 prostate cancers were included. Pre-diagnostic warfarin use ranged from 2.4 to 4.7 %. There was little evidence of any strong association between warfarin use pre-diagnosis and cancer-specific mortality in prostate (adjusted HR 1.03, 95 % CI 0.84-1.26), lung (adjusted HR 1.06, 95 % CI 0.96-1.16), breast (adjusted HR 0.81, 95 % CI 0.62-1.07), or colorectal (adjusted HR 0.88, 95 % CI 0.77-1.01) cancer patients. Dose-response analyses did not reveal consistent evidence of reductions in users of warfarin defined by the number of prescriptions used and daily defined doses.
There was little evidence of associations between pre-diagnostic use of warfarin and cancer-specific mortality in lung, prostate, breast, or colorectal cancer patients.
Cancer Causes and Control 12/2014; 26(3). DOI:10.1007/s10552-014-0511-2 · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This is the protocol for a review and there is no abstract. The objectives are as follows:
The primary objective of this review is to evaluate the effects of non-pharmacological interventions among cancer patients targeted at maintaining cognitive function or ameliorating cognitive impairment as a result of cancer or receipt of systemic cancer treatment (i.e. chemotherapy or hormonal therapies in isolation or combination with other treatments). Patients who have received treatments such as cranial radiation for central nervous system tumours or metastases are not the focus of this review and will be excluded.
A second objective is to evaluate the effectiveness of non-pharmacological interventions for improving non-cognitive outcomes e.g. quality of life among this population.
Thirdly, we will extract and analyse data regarding the duration of intervention effects.
Fourthly, we will examine each study to identify safety as an outcome and incorporate information on intervention safety where possible. Evidence for the review will be based on data from randomised trials.
[Show abstract][Hide abstract] ABSTRACT: Taking medicine to treat symptoms of chronic illness and to prevent worsening of disease is common in older people. However, taking too many medicines can cause harm. This review examines studies in which healthcare professionals have taken action to make sure that older people are receiving the most effective and safest medication for their illness. Actions taken included providing pharmaceutical care, a service provided by pharmacists that involves identifying, preventing and resolving medication-related problems, as well as promoting the correct use of medications and encouraging health promotion and education. Another strategy was computerised decision support, which involves a programme on the doctor’s computer that helps him/her to select appropriate treatment. This review provides limited evidence that interventions, such as pharmaceutical care, may be successful in ensuring that older people are receiving the right medicines, but it is not clear whether this always results in clinical improvement.
[Show abstract][Hide abstract] ABSTRACT: Dietary pattern (DP) analysis allows examination of the combined effects of nutrients and foods on the markers of CVD. Very few studies have examined these relationships during adolescence or young adulthood. Traditional CVD risk biomarkers were analysed in 12-15-year-olds (n 487; Young Hearts (YH)1) and again in the same individuals at 20-25 years of age (n 487; YH3). Based on 7 d diet histories, in the present study, DP analysis was performed using a posteriori principal component analysis for the YH3 cohort and the a priori Mediterranean Diet Score (MDS) was calculated for both YH1 and YH3 cohorts. In the a posteriori DP analysis, YH3 participants adhering most closely to the 'healthy' DP were found to have lower pulse wave velocity (PWV) and homocysteine concentrations, the 'sweet tooth' DP were found to have increased LDL concentrations, systolic blood pressure, and diastolic blood pressure and decreased HDL concentrations, the 'drinker/social' DP were found to have lower LDL and homocysteine concentrations, but exhibited a trend towards a higher TAG concentration, and finally the 'Western' DP were found to have elevated homocysteine and HDL concentrations. In the a priori dietary score analysis, YH3 participants adhering most closely to the Mediterranean diet were found to exhibit a trend towards a lower PWV. MDS did not track between YH1 and YH3, and nor was there a longitudinal relationship between the change in the MDS and the change in CVD risk biomarkers. In conclusion, cross-sectional analysis revealed that some associations between DP and CVD risk biomarkers were already evident in the young adult population, namely the association between the healthy DP (and the MDS) and PWV; however, no longitudinal associations were observed between these relatively short time periods.
British Journal Of Nutrition 09/2014; 112(10):1-14. DOI:10.1017/S0007114514002682 · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AimsTo determine whether the financial incentives for tight glycaemic control, introduced in the UK as part of a pay-for-performance scheme in 2004, increased the rate at which people with newly diagnosed Type 2 diabetes were started on anti-diabetic medication.MethodsA secondary analysis of data from the General Practice Research Database for the years 1999–2008 was performed using an interrupted time series analysis of the treatment patterns for people newly diagnosed with Type 2 diabetes (n=21 197).ResultsOverall, the proportion of people with newly diagnosed diabetes managed without medication 12 months after diagnosis was 47% and after 24 months it was 40%. The annual rate of initiation of pharmacological treatment within 12 months of diagnosis was decreasing before the introduction of the pay-for-performance scheme by 1.2% per year (95% CI -2.0, -0.5%) and increased after the introduction of the scheme by 1.9% per year (95% CI 1.1, 2.7%). The equivalent figures for treatment within 24 months of diagnosis were-1.4% (95% CI -2.1, -0.8%) before the scheme was introduced and 1.6% (95% CI 0.8, 2.3%) after the scheme was introduced.Conclusion
The present study suggests that the introduction of financial incentives in 2004 has effected a change in the management of people newly diagnosed with diabetes. We conclude that a greater proportion of people with newly diagnosed diabetes are being initiated on medication within 1 and 2 years of diagnosis as a result of the introduction of financial incentives for tight glycaemic control.This article is protected by copyright. All rights reserved.
Diabetic Medicine 09/2014; 32(1). DOI:10.1111/dme.12575 · 3.12 Impact Factor