Showing papers by "Andy R Ness published in 2018"

Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks: Meta-analysis of 10 Trials Involving 77 917 Individuals.

Abstract: Importance Current guidelines advocate the use of marine-derived omega-3 fatty acids supplements for the prevention of coronary heart disease and major vascular events in people with prior coronary heart disease, but large trials of omega-3 fatty acids have produced conflicting results. Objective To conduct a meta-analysis of all large trials assessing the associations of omega-3 fatty acid supplements with the risk of fatal and nonfatal coronary heart disease and major vascular events in the full study population and prespecified subgroups. Data Sources and Study Selection This meta-analysis included randomized trials that involved at least 500 participants and a treatment duration of at least 1 year and that assessed associations of omega-3 fatty acids with the risk of vascular events. Data Extraction and Synthesis Aggregated study-level data were obtained from 10 large randomized clinical trials. Rate ratios for each trial were synthesized using observed minus expected statistics and variances. Summary rate ratios were estimated by a fixed-effects meta-analysis using 95% confidence intervals for major diseases and 99% confidence intervals for all subgroups. Main Outcomes and Measures The main outcomes included fatal coronary heart disease, nonfatal myocardial infarction, stroke, major vascular events, and all-cause mortality, as well as major vascular events in study population subgroups. Results Of the 77 917 high-risk individuals participating in the 10 trials, 47 803 (61.4%) were men, and the mean age at entry was 64.0 years; the trials lasted a mean of 4.4 years. The associations of treatment with outcomes were assessed on 6273 coronary heart disease events (2695 coronary heart disease deaths and 2276 nonfatal myocardial infarctions) and 12 001 major vascular events. Randomization to omega-3 fatty acid supplementation (eicosapentaenoic acid dose range, 226-1800 mg/d) had no significant associations with coronary heart disease death (rate ratio [RR], 0.93; 99% CI, 0.83-1.03; P = .05), nonfatal myocardial infarction (RR, 0.97; 99% CI, 0.87-1.08; P = .43) or any coronary heart disease events (RR, 0.96; 95% CI, 0.90-1.01; P = .12). Neither did randomization to omega-3 fatty acid supplementation have any significant associations with major vascular events (RR, 0.97; 95% CI, 0.93-1.01; P = .10), overall or in any subgroups, including subgroups composed of persons with prior coronary heart disease, diabetes, lipid levels greater than a given cutoff level, or statin use. Conclusions and Relevance This meta-analysis demonstrated that omega-3 fatty acids had no significant association with fatal or nonfatal coronary heart disease or any major vascular events. It provides no support for current recommendations for the use of such supplements in people with a history of coronary heart disease.

Tobacco smoking and alcohol drinking at diagnosis of head and neck cancer and all-cause mortality: Results from head and neck 5000, a prospective observational cohort of people with head and neck cancer.

Abstract: Tobacco smoking and alcohol consumption are well-established risk factors for head and neck cancer. The prognostic role of smoking and alcohol intake at diagnosis have been less well studied. We analysed 1,393 people prospectively enrolled into the Head and Neck 5000 study (oral cavity cancer, n=403; oropharyngeal cancer, n=660; laryngeal cancer, n=330) and followed up for a median of 3.5 years. The primary outcome was all-cause mortality. We used Cox proportional hazard models to derive minimally adjusted (age and gender) and fully adjusted (age, gender, ethnicity, stage, comorbidity, body mass index, HPV status, treatment, education, deprivation index, income, marital status, and either smoking or alcohol use) mortality hazard ratios (HR) for the effects of smoking status and alcohol intake at diagnosis. Models were stratified by cancer site, stage and HPV status. The fully-adjusted HR for current versus never-smokers was 1.7 overall (95% confidence interval [CI] 1.1, 2.6). In stratified analyses, associations of smoking with mortality were observed for oropharyngeal and laryngeal cancers (fully adjusted HRs for current smokers: 1.8 (95% CI=0.9, 3.40 and 2.3 (95% CI=0.8, 6.4)). We found no evidence that people who drank hazardous to harmful amounts of alcohol at diagnosis had a higher mortality risk compared to non-drinkers (HR=1.2 (95% CI=0.9, 1.6)). There was no strong evidence that HPV status or tumour stage modified the association of smoking with survival. Smoking status at the time of a head and neck cancer diagnosis influenced all-cause mortality in models adjusted for important prognostic factors.

Early enteral nutrition within 24 hours of lower gastrointestinal surgery versus later commencement for length of hospital stay and postoperative complications.

Abstract: BACKGROUND This is an update of the review last published in 2011. It focuses on early postoperative enteral nutrition after lower gastrointestinal surgery. Traditional management consisted of 'nil by mouth', where patients receive fluids followed by solids after bowel function has returned. Although several trials have reported lower incidence of infectious complications and faster wound healing upon early feeding, other trials have shown no effect. The immediate advantage of energy intake (carbohydrates, protein or fat) could enhance recovery with fewer complications, and this warrants a systematic evaluation. OBJECTIVES To evaluate whether early commencement of postoperative enteral nutrition (within 24 hours), oral intake and any kind of tube feeding (gastric, duodenal or jejunal), compared with traditional management (delayed nutritional supply) is associated with a shorter length of hospital stay (LoS), fewer complications, mortality and adverse events in patients undergoing lower gastrointestinal surgery (distal to the ligament of Treitz). SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library 2017, issue 10), Ovid MEDLINE (1950 to 15 November 2017), Ovid Embase (1974 to 15 November 2017). We also searched for ongoing trials in ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform (15 November 2017). We handsearched reference lists of identified studies and previous systematic reviews. SELECTION CRITERIA We included randomised controlled trials (RCT) comparing early commencement of enteral nutrition (within 24 hours) with no feeding in adult participants undergoing lower gastrointestinal surgery. DATA COLLECTION AND ANALYSIS Two review authors independently assessed study quality using the Cochrane 'Risk of bias' tool tailored to this review and extracted data. Data analyses were conducted according to the Cochrane recommendations.We rated the quality of evidence according to GRADE.Primary outcomes were LoS and postoperative complications (wound infections, intraabdominal abscesses, anastomotic dehiscence, pneumonia).Secondary outcomes were: mortality, adverse events (nausea, vomiting), and quality of life (QoL).LoS was estimated using mean difference (MD (presented as mean +/- SD). For other outcomes we estimated the common risk ratio (RR) and calculated the associated 95% confidence intervals. For analysis, we used an inverse-variance random-effects model for the primary outcome (LoS) and Mantel-Haenszel random-effects models for the secondary outcomes. We also performed Trial Sequential Analyses (TSA). MAIN RESULTS We identified 17 RCTs with 1437 participants undergoing lower gastrointestinal surgery. Most studies were at high or unclear risk of bias in two or more domains. Six studies were judged as having low risk of selection bias for random sequence generation and insufficient details were provided for judgement on allocation concealment in all 17 studies. With regards to performance and deception bias; 14 studies reported no attempt to blind participants and blinding of personnel was not discussed either. Only one study was judged as low risk of bias for blinding of outcome assessor. With regards to incomplete outcome data, three studies were judged to be at high risk because they had more than 10% difference in missing data between groups. For selective reporting, nine studies were judged as unclear as protocols were not provided and eight studies had issues with either missing data or incomplete reporting of results.LOS was reported in 16 studies (1346 participants). The mean LoS ranged from four days to 16 days in the early feeding groups and from 6.6 days to 23.5 days in the control groups. Mean difference (MD) in LoS was 1.95 (95% CI, -2.99 to -0.91, P < 0.001) days shorter in the early feeding group. However, there was substantial heterogeneity between included studies (I2 = 81, %, Chi2 = 78.98, P < 0.00001), thus the overall quality of evidence for LoS is low. These results were confirmed by the TSA showing that the cumulative Z-curve crossed the trial sequential monitoring boundary for benefit.We found no differences in the incidence of postoperative complications: wound infection (12 studies, 1181 participants, RR 0.99, 95%CI 0.64 to 1.52, very low-quality evidence), intraabdominal abscesses (6 studies, 554 participants, RR 1.00, 95%CI 0.26 to 3.80, low-quality evidence), anastomotic leakage/dehiscence (13 studies, 1232 participants, RR 0.78, 95%CI 0.38 to 1.61, low-quality evidence; number needed to treat for an additional beneficial outcome (NNTB) = 100), and pneumonia (10 studies, 954 participants, RR 0.88, 95%CI 0.32 to 2.42, low-quality evidence; NNTB = 333).Mortality was reported in 12 studies (1179 participants), and showed no between-group differences (RR = 0.56, 95%CI, 0.21 to 1.52, P = 0.26, I2 = 0%, Chi2 = 3.08, P = 0.96, low-quality evidence). The most commonly reported cause of death was anastomotic leakage, sepsis and acute myocardial infarction.Seven studies (613 participants) reported vomiting (RR 1.23, 95%CI, 0.96 to 1.58, P = 0.10, I2 = 0%, Chi2 = 4.98, P = 0.55, low-quality evidence; number needed to treat for an additional harmful outcome (NNTH) = 19), and two studies (118 participants) reported nausea (RR 0.95, 0.71 to 1.26, low-quality evidence). Four studies reported combined nausea and vomiting (RR 0.94, 95%CI 0.51 to 1.74, very low-quality evidence). One study reported QoL assessment; the scores did not differ between groups at 30 days after discharge on either QoL scale EORTC QLQ-C30 or EORTC QlQ-OV28 (very low-quality evidence). AUTHORS' CONCLUSIONS This review suggests that early enteral feeding may lead to a reduced postoperative LoS, however cautious interpretation must be taken due to substantial heterogeneity and low-quality evidence. For all other outcomes (postoperative complications, mortality, adverse events, and QoL) the findings are inconclusive, and further trials are justified to enhance the understanding of early feeding for these. In this updated review, only a few additional studies have been included, and these were small and of poor quality.To improve the evidence, future trials should address quality issues and focus on clearly defining and measuring postoperative complications to allow for better comparison between studies. However due to the introduction of fast track protocols which already include an early feeding component, future trials may be challenging. A more feasible trial may be to investigate the effect of differing postoperative energy intake regimens on relevant outcomes.

The long-term impact of folic acid in pregnancy on offspring DNA methylation: Follow-up of the Aberdeen folic acid supplementation trial (AFAST)

Abstract: Funding This work was supported by the NIHR Bristol Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. R.C.R., G.C.S., N.K., T.G., G.D.S. and C.L.R. work in a unit that receives funds from the University of Bristol and the UK Medical Research Council (MC_UU_12013/1, MC_UU_12013/2 and MC_UU_12013/8). This work was also supported by CRUK (grant number C18281/A19169) and the ESRC (grant number ES/N000498/1). C.M.T. is supported by a Wellcome Trust Career Re-entry Fellowship (grant number 104077/Z/14/Z).

Depressive symptoms in relation to overall survival in people with head and neck cancer: A longitudinal cohort study

Abstract: Objective The objective of the study is to investigate the relation between pretreatment depressive symptoms (DS) and the course of DS during the first year after cancer diagnosis, and overall survival among people with head and neck cancer (HNC). Methods Data from the Head and Neck 5000 prospective clinical cohort study were used. Depressive symptoms were measured using the Hospital Anxiety and Depression Scale (HADS) pretreatment, at 4 and 12-month follow-up. Also, socio-demographic, clinical, lifestyle, and mortality data were collected. The association between before start of treatment DS (HADS-depression > 7) and course (never DS, recovered from DS, or persistent/recurrent/late DS at 12-month follow-up) and survival was investigated using Cox regression. Unadjusted and adjusted analyses were performed. Results In total, 384 of the 2144 persons (18%) reported pretreatment DS. Regarding DS course, 63% never had DS, 16% recovered, and 20% had persistent/recurrent/late DS. People with pretreatment DS had a higher risk of earlier death than people without DS (hazard ratio (HR) = 1.65; 95% confidence interval (CI) 1.33-2.05), but this decreased after correcting for socio-demographic, clinical, and lifestyle-related factors (HR = 1.21; 95% CI 0.97-1.52). Regarding the course of DS, people with persistent/recurrent/late DS had a higher risk of earlier death (HR = 2.04; 95% CI 1.36-3.05), while people who recovered had a comparable risk (HR = 1.12; 95% CI 0.66-1.90) as the reference group who never experienced DS. After correcting for socio-demographic and clinical factors, people with persistent/recurrent/late DS still had a higher risk of earlier death (HR = 1.66; 95% CI 1.09-2.53). Conclusions Pretreatment DS and persistent/recurrent/late DS were associated with worse survival among people with HNC.

Using the normalization process theory to qualitatively explore sense-making in implementation of the enhanced recovery after surgery programme: "it’s not rocket science"

Abstract: Introduction The Enhanced Recovery After Surgery programme (ERAS) is an approach to the perioperative care of patients encompassing multiple interventions and involving a wide range of different actors. It can thus be defined as a complex intervention. Despite the strength of the evidence-base in its support, the implementation of ERAS has been slow. This paper specifically explores the utility of Normalization Process Theory (NPT) as a methodological framework to aid exploration of ERAS implementation, with a focus on the core NPT construct coherence. Methods and materials The study employed qualitative methods guided by NPT. Semi-structured interviews were conducted with twenty-six healthcare professionals working in three specialities (thoracic, colorectal, head and neck) in a UK hospital. Data were analysed using an adapted Framework Approach. Results Coherence, or sense-making work, was key to successful implementation and demonstrated in the importance of participants believing in ERAS both as an individual and as a team. In order to invest in ERAS individuals needed to be able to differentiate its practices favourably with those enacted pre-implementation (differentiation). Participants also needed to understand their specific tasks and responsibilities (individual specification) and build a shared understanding (communal specification), resolving differences in planning meetings. Belief in the worth of ERAS was often aligned to evidence for its effectiveness or benefit to patients (internalization), so implementing ERAS therefore 'made sense'. Sense-making work had strong links with aspects of implementation related to other NPT constructs including resource issues such as funding for data collection and feedback (reflexive monitoring: systemization) and failure to replace key staff members (collective action: skill set workability). Conclusions NPT was found to be a valuable heuristic device to employ in the exploration of ERAS implementation processes. NPT was useful in facilitating recognition of the importance of coherence work to successful implementation. However despite participants' strong beliefs in the worth of ERAS, it was in translating these beliefs into action that barriers were encountered, highlighting the interconnectedness of NPT constructs and the complicated nature of implementing complex interventions.

Shared heritability and functional enrichment across six solid cancers

Abstract: Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg=0.57, p=4.6x10-8), breast and ovarian cancer (rg=0.24, p=7x10-5), breast and lung cancer (rg=0.18, p=1.5x10-6) and breast and colorectal cancer (rg=0.15, p=1.1x10-4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.

Systematic review evaluating randomized controlled trials of smoking and alcohol cessation interventions in people with head and neck cancer and oral dysplasia

Abstract: Background Smoking and alcohol increase the risk of head and neck cancer and affect treatment outcomes. Interventions modifying these behaviors may improve posttreatment outcomes and survival. We systematically reviewed evidence of the effectiveness of smoking/alcohol interventions in head and neck cancer and oral dysplasia. Methods The AMED, CINAHL, Embase, MEDLINE, and Web of Science databases were searched for randomized controlled trials (RCTs) of smoking/alcohol interventions in people with head and neck cancer. A qualitative synthesis of the studies was conducted. Results Three RCTs were identified: 2 smoking interventions and 1 smoking and alcohol intervention. One intervention, which was comprised of a smoking intervention based on Cognitive Behavioral Therapy and pharmacologic management compared to usual care, reduced smoking prevalence. Conclusion Further research is required into the underlying mechanisms that lead to cessation and interventions that include both pharmacological and behavioral therapy. Future RCTs should include suitable control conditions and sufficient power to assess clinical outcomes.

Change in alcohol and tobacco consumption after a diagnosis of head and neck cancer: Findings from Head and Neck 5000

Abstract: Background Tobacco and alcohol consumption are risk factors for developing head and neck cancer, and continuation postdiagnosis can adversely affect prognosis. We explored changes to these behaviors after a head and neck cancer diagnosis. Methods Demographic and clinical data were collected from 973 people newly diagnosed with oral cavity, oropharyngeal, or laryngeal cancer. Tobacco and alcohol consumption were additionally collected 4 and 12 months later. Results The prevalence of high alcohol consumption reduced from 54.3% at diagnosis to 41.4% at 12 months, and smoking reduced from 21.0% to 11.7%. Changes in behavior were dynamic, for example, 44% of smokers at 12 months were not smoking at diagnosis or 4 months. Several factors were associated with alcohol consumption, whereas only tumor site and comorbidities were associated with smoking. Conclusion A diagnosis of head and neck cancer can result in important changes in alcohol consumption and smoking prevalence. However, these changes are dynamic in the first year after diagnosis.

The changing aetiology of head and neck squamous cell cancer: A tale of three cancers?

Abstract: Head and neck cancers are the sixth most common cancers worldwide and an important cause of ill health.(1) Each year about 9000 cases are reported in the UK.(2) Survival is poor and despite advances in treatment, has not improved until recently.(3) The majority of head and neck cancers are squamous cell carcinomas, affecting the larynx, oropharynx and oral cavity. The aetiology is changing and this has implications for prevention and treatment. Twenty years ago, tobacco and alcohol consumption were considered to be the established risk factors and it was estimated that these risk factors accounted for about 75% of cases.(4) More recently human papillomavirus (HPV) has emerged as a likely cause of oropharyngeal cancer.(4) Here we argue that each cancer site is predicted differently by smoking, alcohol and sexual behaviour. We also suggest that these risk factors do not fully explain the changing pattern of disease observed in the UK. This article is protected by copyright. All rights reserved.

Pilot trials in physical activity journals: a review of reporting and editorial policy.

Abstract: Since the early 2000s, a number of publications in the medical literature have highlighted inadequacies in the design, conduct and reporting of pilot trials. This work led to two notable publications in 2016: a conceptual framework for defining feasibility studies and an extension to the CONSORT 2010 statement to include pilot trials. It was hoped that these publications would educate researchers, leading to better use of pilot trials and thus more rigorously planned and informed randomised controlled trials. The aim of the present work is to evaluate the impact of these publications in the field of physical activity by reviewing the literature pre- and post-2016. This first article presents the pre-2016 review of the reporting and the current editorial policy applied to pilot trials published in physical activity journals. Fourteen physical activity journals were screened for pilot and feasibility studies published between 2012 and 2015. The CONSORT 2010 extension to pilot and feasibility studies was used as a framework to assess the reporting quality of the studies. Editors of the eligible physical activity journals were canvassed regarding their editorial policy for pilot and feasibility studies. Thirty-one articles across five journals met the eligibility criteria. These articles fell into three distinct categories: trials that were carried out in preparation for a future definitive trial (23%), trials that evaluated the feasibility of a novel intervention but did not explicitly address a future definitive trial (23%) and trials that did not have any clear objectives to address feasibility (55%). Editors from all five journals stated that they generally do not accept pilot trials, and none gave reference to the CONSORT 2010 extension as a guideline for submissions. The result that over half of the studies did not have feasibility objectives is in line with previous research findings, demonstrating that these findings are not being disseminated effectively to researchers in the field of physical activity. The low standard of reporting across most reviewed articles and the neglect of the extended CONSORT 2010 statement by the journal editors highlight the need to actively disseminate these guidelines to ensure their impact.

Closing the Loop on Centralization of Cleft Care in the United Kingdom

Abstract: Objective:We highlight a major study that investigated the impact of reconfigured cleft care in the United Kingdom some 15 years after centralization. We argue that centralization as an interventio...

Physical activity at age 11 years and chronic disabling fatigue at ages 13 and 16 years in a UK birth cohort

Abstract: Objective To investigate associations of physical activity at age 11 years with chronic disabling fatigue (CDF) at ages 13 and 16 years Design Longitudinal birth cohort Setting South-West England Participants Adolescents enrolled in the Avon Longitudinal Study of Parents and Children Outcomes and exposures We identified adolescents who had disabling fatigue of >6 months9 duration without a known cause at ages 13 and 16 years Total and moderate-to-vigorous physical activity and sedentary time at age 11 years were measured by accelerometry over a 7-day period Results A total physical activity level 100 counts/min higher at age 11 years was associated with 25% lower odds of CDF at age 13 years (OR=075 (95% CI 059 to 095)), a 1% increase in the proportion of monitored time spent in moderate-to-vigorous activity was associated with 16% lower odds of CDF (OR=084 (95% CI 069 to 101)) and a 1-hour increase in sedentary time was associated with 35% higher odds of CDF (OR=135 (95% CI 102 to 179)) Disabling fatigue of only 3–5 months’ duration at age 13 years had weaker associations with physical activity, and CDF at age 16 years was not associated with physical activity at age 11 years Conclusions Children who had chronic disabling fatigue at age 13 years had lower levels of total and moderate-to-vigorous physical activity and more sedentary time 2 years previously, but this association could be explained by reverse causation

Nutritools.org an innovative website including a Food Questionnaire Creator for dietary assessment in health research

Abstract: Accurate diet measurement is challenging and strategies to support researchers in selecting the most appropriate dietary assessment tools (DATs) are required. DIET@NET (DIETary Assessment tools NETwork) partnership aimed to create an online resource that provides guidelines for selecting tools with access to validated DATs. The Nutritools website(1) (www.nutritools.org), was developed using 3 approaches. 1) Creation of Best Practice Guidelines(2), enabling researchers to choose the most appropriate DAT for their work. These were generated using the Delphi method which enabled integration of expert views. 2) Creating an interactive DAT e-library, with the DATs being identified through a systematic review of systematic reviews(3). Bubble charts and summary plots are used to compare DATs. 3) Development of a Food Questionnaire Creator (FQC), an online interface between food tables and the DATs which allows users to create their own food questionnaires. This work was overseen by the DIET@NET partnership. Other useful information includes links to food composition databases and a detailed glossary of terms. Results from the systematic review of reviews generated information for Nutritools. The website includes 127 international validated tools, of which 63 tools were validated in the UK (with 45 validated from year 2000 onwards). The majority (n = 34) of the validated tools were food frequency questionnaires, developed from 1981 to 2016. Numbers of foods included ranged from 8–692 items. Five of the 12 dietary recalls included were web-based. Tools were usually validated against another self-reported dietary assessment method, mainly weighed food diaries. More than 1500 papers with non-UK tools were identified, of these, data on 64 international tools and their validation studies were added to Nutritools. The FQC allows for food questionnaires to be created using data from the UK National Diet and Nutrition Survey (NDNS) Year 6 and the Composition of Foods Integrated Dataset. Results from the NDNS can be used to formulate food questions that capture a large proportion of the nutrients of interest and to inform portion sizes. In conclusion, Nutritools (www.nutritools.org), is an online platform that hosts international validated and interactive DATs. Researchers can use the interactive Best Practice Guidelines and features in the selection of the most appropriate DAT for their study, and the Food Questionnaire Creator to develop their own online food questionnaires. This project was funded by the Medical Research Council (MRC) (ref: MR/L02019X/1). 1. Warthon-Medina M, Hooson J, Hancock N, et al. (2017) The Lancet 390, pS94. 2. Cade JE, Warthon-Medina M, Albar S, et al. (2017) BMC Medicine 15(1), p202. 3. Hooson J, Hancock N, Greenwood DC, et al. (2016) Proc Nutr Soc 75(OCE3).