Underage Adolescents' Reactions to Adverts for Beer and Spirit Brands and Associations with Higher Risk Drinking and Susceptibility to Drink: A Cross-Sectional Study in the UK.

AIMS: In the UK, adolescents under the minimum legal purchasing age (<18 years) are aware of a variety of alcohol marketing activities. It is therefore important to examine how such marketing appeals and how it might shape consumption. This study assessed the relationships between positive reactions to alcohol adverts and susceptibility to drink among never drinkers and higher-risk drinking among current drinkers. METHODS: Online cross-sectional survey of 11-17 year olds (n = 2582) in the UK. Adolescents were shown three video alcohol adverts (Fosters Radler/Haig Club Clubman/Smirnoff). Reactions to each were measured by eight scale-items (e.g. 1 = makes [Brand] seem unappealing to 5 = makes [Brand] seem appealing), which were combined into a composite score (coded: positive versus other). Logistic regressions assessed associations between overall positive advert reactions and drinking behaviours. RESULTS: Half of adolescents had overall positive reactions to the Smirnoff (52%) and Fosters (53%) adverts, and a third (34%) had a positive reaction to the Haig Club advert. Across all three adverts, positive reactions were associated with ~1.5 times increased odds of being susceptible to drink among never drinkers. Among current drinkers, positive reactions to the Foster's Radler and Haig Club adverts were associated with around 1.4 times increased odds of being a higher-risk drinker. CONCLUSIONS: These alcohol advertisements commonly appealed to underage adolescents, and these reactions were associated with susceptibility among never drinkers and higher-risk consumption among current drinkers. Regulatory consideration should be given to what messages are permitted in alcohol advertising, including international alternatives (e.g. only factual information).

Understanding and managing fish populations: keeping the toolbox fit for purpose.

Wild fish populations are currently experiencing unprecedented pressures, which are projected to intensify in the coming decades. Developing a thorough understanding of the influences of both biotic and abiotic factors on fish populations is a salient issue in contemporary fish conservation and management. During the 50th Anniversary Symposium of The Fisheries Society of the British Isles at the University of Exeter, UK, in July 2017, scientists from diverse research backgrounds gathered to discuss key topics under the broad umbrella of 'Understanding Fish Populations'. Below, the output of one such discussion group is detailed, focusing on tools used to investigate natural fish populations. Five main groups of approaches were identified: tagging and telemetry; molecular tools; survey tools; statistical and modelling tools; tissue analyses. The appraisal covered current challenges and potential solutions for each of these topics. In addition, three key themes were identified as applicable across all tool-based applications. These included data management, public engagement, and fisheries policy and governance. The continued innovation of tools and capacity to integrate interdisciplinary approaches into the future assessment and management of fish populations is highlighted as an important focus for the next 50 years of fisheries research.

Quantifying loading, toxic concentrations, and systemic persistence of chloride in a contemporary mixed-land-use watershed using an experimental watershed approach.

A nested-scale experimental watershed study was implemented to quantify loading and persistence of chloride in an urbanizing, mixed-land-use watershed. A Midwest USA (Missouri) watershed was partitioned into five sub-basins with contrasting dominant land use. Streamwater was tested for chloride concentration four days per week from October 2009 through May 2014 at each site. Monitoring sites included co-located gauging and climate stations recording variables at 30-minute intervals. Results indicate significant (p<0.01) differences in chloride concentrations and loading between sites. Loading consistently increased from the forested headwaters (average=507kgday-1) to primarily urban watershed terminus (average=7501kgday-1). Chloride concentrations were highest (average=83.9mgL-1) with the greatest frequency of acutely toxic conditions (i.e. 860mgL-1) mid-watershed. This finding is in-part attributable to the ratio of chloride application to streamflow volume (i.e. increasing flow volume with stream distance resulted in chloride dilution, offsetting increased percent urban land use with stream distance). Results highlight the important, yet often confounding, interactions between pollutant loading and flow dynamics. Chloride peaks occurred during late winter/early spring melting periods, implicating road salt application as the primary contributor to the chloride regime. Floodplain groundwater analysis indicated seasonal sink/source relationships between the stream and floodplain, which could contribute to chronic toxicity and persistent low Cl- concentrations in streamwater year-round. Results hold important implications for resource managers wishing to mitigate water quality and aquatic habitat degradation, and suggest important water quality limitations to stream restoration success in complex urban aquatic ecosystems.

Assessment of a Self-Reported Drinks Diary for the Estimation of Drinks Intake by Care Home Residents: Fluid Intake Study in the Elderly (FISE).

OBJECTIVES: We evaluated the accuracy of a newly developed self-completed Drinks Diary in care home residents and compared it with direct observation and fluid intake charts. DESIGN: Observational study. SETTING: Residential care homes in Norfolk, UK. PARTICIPANTS: 22 elderly people (18 women, mean age 86.6 years SD 8.6, 12 with MMSE scores <27). MEASUREMENTS: Participants recorded their own drinks intake over 24 hours using the Drinks Diary while care staff used the homes' usual fluid intake chart to record drinks intake. These records were compared with drinks intake assessed by researcher direct observation (reference method), during waking hours (6am to 10pm), while drinks taken from 10pm to 6am were self-reported and checked with staff. RESULTS: Drinks intake assessed by the Drinks Diary was highly correlated with researcher direct observation (Pearson correlation coefficient r=0.93, p<0.001, mean difference -163ml/day) while few staff-completed fluid charts were returned and correlation was low (r=0.122, p=0.818, mean difference 702ml/day). The Drinks Diary classified 19 of 22 participants correctly as drinking enough or not using both the European Food Safety Authority and US recommendations. CONCLUSION: The Drinks Diary estimate of drinks intake was comparable with direct observation and more accurate (and reliably completed) than staff records. The Drinks Diary can provide a reliable estimate of drinks intake in elderly care home residents physically and cognitively able to complete it. It may be useful for researchers, care staff and practitioners needing to monitor drinks intake of elderly people, to help them avoid dehydration.

British Dietetic Association evidence-based guidelines for the protein requirements of adults undergoing maintenance haemodialysis or peritoneal dialysis.

BACKGROUND: Existing nutritional guidelines suggest that protein requirements of adults with stage five chronic kidney disease undergoing haemodialysis (HD) or peritoneal dialysis (PD) are increased as a result of protein losses during dialysis. The present review aimed to update previous guidance and develop evidence-based practice guidelines on the protein requirements of adults undergoing maintenance dialysis. METHODS: Following a PICO approach (Participants or Population, Intervention or Exposure, Comparison and Outcome), four research questions were formulated to investigate the total protein requirement and protein quality required by adults undergoing HD and PD. A comprehensive, systematic review was undertaken using the databases Medline, EMBASE and the Cochrane Library from 2005 to September 2009 for HD studies and from 1997 to September 2009 for PD studies. RESULTS: The literature search yielded 2931 studies, which were assessed for inclusion. Following appraisal, 19 studies in HD and 18 studies in PD met the inclusion criteria and were systematically reviewed. Limited good quality evidence supports the recommendations that: (i) adults undergoing maintenance HD require a minimum protein intake of 1.1 g kg(-1) ideal body weight (IBW) per day; and (ii) adults undergoing maintenance PD require a minimum protein intake of 1.0-1.2 kg(-1) IBW per day, in conjunction with an adequate energy intake. There were no studies that addressed the quality of protein for either HD or PD. CONCLUSIONS: Evidence suggests that nutritional status may be maintained with lower protein intakes than previously recommended. However, the evidence base is limited and further randomised controlled trials are required to establish the optimal protein intake for dialysis patients.

Low glycaemic index diets and blood lipids: a systematic review and meta-analysis of randomised controlled trials.

AIMS: Low glycaemic index (GI) diets are beneficial in the management of hyperglycemia. Cardiovascular diseases are the major cause of mortality in diabetes therefore it is important to understand the effects of GI on blood lipids. The aim was to systematically review randomised controlled trials (RCTs) of low GI diets on blood lipids. DATA SYNTHESIS: We searched OVID Medline, Embase and Cochrane library to March 2012. Random effects meta-analyses were performed on twenty-eight RCTs comparing low- with high GI diets over at least 4 weeks (1272 participants; studies ranged from 6 to 155 participants); one was powered on blood lipids, 3 had adequate allocation concealment. Low GI diets significantly reduced total (-0.13 mmol/l, 95%CI -0.22 to -0.04, P = 0.004, 27 trials, 1441 participants, I(2) = 0%) and LDL-cholesterol (-0.16 mmol/l, 95%CI -0.24 to -0.08, P < 0.0001, 23 trials, 1281 participants, I(2) = 0%) compared with high GI diets and independently of weight loss. Subgroup analyses suggest that reductions in LDL-C are greatest in studies of shortest duration and greatest magnitude of GI reduction. Furthermore, lipid improvements appear greatest and most reliable when the low GI intervention is accompanied by an increase in dietary fibre. Sensitivity analyses, removing studies without adequate allocation concealment, lost statistical significance but retained suggested mean falls of ~0.10 mmol/l in both. There were no effects on HDL-cholesterol (MD -0.03 mmol/l, 95%CI -0.06 to 0.00, I(2) = 0%), or triglycerides (MD 0.01 mmol/l, 95%CI -0.06 to 0.08, I(2) = 0%). CONCLUSIONS: This meta-analysis provides consistent evidence that low GI diets reduce total and LDL-cholesterol and have no effect on HDL-cholesterol or triglycerides.

Coherent supercontinuum generation in photonic crystal fiber with all-normal group velocity dispersion.

We demonstrate supercontinuum generation in a photonic crystal fiber with all-normal group velocity dispersion. Pumping a short section of this fiber with compressed pulses from a compact amplified fiber laser generates a 200 nm bandwidth continuum with typical self-phase-modulation characteristics. We demonstrate that the supercontinuum is compressible to a duration of 26 fs. It therefore has a high degree of coherence between all the frequency components, and is a single pulse in the time domain. A smooth, flat spectrum spanning 800 nm is achieved using a longer piece of fiber.

A review of how to conduct a surgical survey using a questionnaire.

Health surveys using questionnaires facilitate the acquisition of information on the knowledge, behaviour, attitudes, perceptions and clinical history of a selected population. Their internal and external validities are threatened by poor design and low response rates. Numerous studies have investigated survey design and administration but care should be taken when generalising findings in different clinical and cultural settings. The current evidence-base suggests that no single mode of survey administration, such as postal, electronic or telephone, is superior to another. Whilst there is no evidence of an ideal response rate relationship to survey validity, response rates can be enhanced by including monetary incentives, providing a time cue, and repeat contact with non-responders. Unlike other modes of experimental data collection, few guidelines currently exist for survey and questionnaire design and response rate should not be considered a direct measure of a survey's quality.

Dissemination and publication of research findings: an updated review of related biases.

OBJECTIVES: To identify and appraise empirical studies on publication and related biases published since 1998; to assess methods to deal with publication and related biases; and to examine, in a random sample of published systematic reviews, measures taken to prevent, reduce and detect dissemination bias. DATA SOURCES: The main literature search, in August 2008, covered the Cochrane Methodology Register Database, MEDLINE, EMBASE, AMED and CINAHL. In May 2009, PubMed, PsycINFO and OpenSIGLE were also searched. Reference lists of retrieved studies were also examined. REVIEW METHODS: In Part I, studies were classified as evidence or method studies and data were extracted according to types of dissemination bias or methods for dealing with it. Evidence from empirical studies was summarised narratively. In Part II, 300 systematic reviews were randomly selected from MEDLINE and the methods used to deal with publication and related biases were assessed. RESULTS: Studies with significant or positive results were more likely to be published than those with non-significant or negative results, thereby confirming findings from a previous HTA report. There was convincing evidence that outcome reporting bias exists and has an impact on the pooled summary in systematic reviews. Studies with significant results tended to be published earlier than studies with non-significant results, and empirical evidence suggests that published studies tended to report a greater treatment effect than those from the grey literature. Exclusion of non-English-language studies appeared to result in a high risk of bias in some areas of research such as complementary and alternative medicine. In a few cases, publication and related biases had a potentially detrimental impact on patients or resource use. Publication bias can be prevented before a literature review (e.g. by prospective registration of trials), or detected during a literature review (e.g. by locating unpublished studies, funnel plot and related tests, sensitivity analysis modelling), or its impact can be minimised after a literature review (e.g. by confirmatory large-scale trials, updating the systematic review). The interpretation of funnel plot and related statistical tests, often used to assess publication bias, was often too simplistic and likely misleading. More sophisticated modelling methods have not been widely used. Compared with systematic reviews published in 1996, recent reviews of health-care interventions were more likely to locate and include non-English-language studies and grey literature or unpublished studies, and to test for publication bias. CONCLUSIONS: Dissemination of research findings is likely to be a biased process, although the actual impact of such bias depends on specific circumstances. The prospective registration of clinical trials and the endorsement of reporting guidelines may reduce research dissemination bias in clinical research. In systematic reviews, measures can be taken to minimise the impact of dissemination bias by systematically searching for and including relevant studies that are difficult to access. Statistical methods can be useful for sensitivity analyses. Further research is needed to develop methods for qualitatively assessing the risk of publication bias in systematic reviews, and to evaluate the effect of prospective registration of studies, open access policy and improved publication guidelines.

Effects of soy protein and isoflavones on circulating hormone concentrations in pre- and post-menopausal women: a systematic review and meta-analysis.

BACKGROUND Hormonal effects of soy and isoflavones have been investigated in numerous trials with equivocal findings. We aimed to systematically assess the effects of soy and isoflavones on circulating estrogen and other hormones in pre- and post-menopausal women. METHODS The Cochrane Library, MEDLINE and EMBASE (plus reviews and experts) were searched to December 2007. Inclusion of randomized or residential crossover trials of soy or isoflavones for 4 or more weeks on estrogens, SHBG, FSH, LH, progesterone and thyroid hormones in women was assessed independently in duplicate. Six percent of papers assessed were included. Data concerning participants, interventions, outcomes, potential effect modifiers and trial quality characteristics were extracted independently in duplicate. RESULTS Forty-seven studies (11 of pre-, 35 of post- and 1 of perimenopausal women) were included. In premenopausal women, meta-analysis suggested that soy or isoflavone consumption did not affect primary outcomes estradiol, estrone or SHBG concentrations, but significantly reduced secondary outcomes FSH and LH [by approximately 20% using standardized mean difference (SMD), P = 0.01 and 0.05, respectively]. Menstrual cycle length was increased by 1.05 days (95% CI 0.13, 1.97, 10 studies). In post-menopausal women, there were no statistically significant effects on estradiol, estrone, SHBG, FSH or LH, although there was a small statistically non-significant increase in total estradiol with soy or isoflavones ( approximately 14%, SMD, P = 0.07, 21 studies). CONCLUSIONS Isoflavone-rich soy products decrease FSH and LH in premenopausal women and may increase estradiol in post-menopausal women. The clinical implications of these modest hormonal changes remain to be determined.

Multi-layered regulation of intestinal antimicrobial defense.

The gastrointestinal tract of mammals is heavily colonized with a complex and dynamic microbial community. To cope with this complex microbial challenge, multiple epithelial lineages, such as enterocytes and Paneth cells, elaborate a diverse repertoire of protein antibiotics. The gut antimicrobial arsenal encompasses multiple protein families, including defensins, cathelicidins, and C-type lectins. These antimicrobial peptides and proteins play a key role in protecting the host against pathogen challenge, and likely also function to limit invasion of indigenous microbes. It is becoming increasingly apparent that expression of mucosal antimicrobial defenses is tightly controlled. This occurs at multiple levels, including transcriptional regulation in response to bacterial cues, post-translational proteolytic processing, and bacterial regulation of Paneth cell degranulation. Impaired antimicrobial peptide expression has also been implicated in inflammatory bowel disease, underscoring the essential role of antimicrobial defenses in maintaining intestinal homeostasis.

Genetic associations in peripheral joint osteoarthritis and spinal degenerative disease: a systematic review.

UNLABELLED: We conducted a systematic review of genetic association studies for osteoarthritis of the peripheral joints (OA) and spinal degenerative disease (SDD). Electronic searches were carried out for any English language article reporting on a gene association study for either OA or SDD published up until the end of 2006. A team of seven reviewers used a standardised template to extract data in duplicate. In all, 90 studies fulfilled our inclusion criteria, reporting a total of 94 significant associations from 83 different genes. We found relatively few instances in which a specific gene-disease association had been analysed by more than one study, and there were 14 cases in which significant associations were replicated in independent studies (at joints associated with the AGC1, ASPN, COL9A2, COL9A3, COL11A2, ESR1, FZRB, HFE, IL1A, IL1RN, PTGS2 and VDR genes). METHOD: logical and reporting problems were widespread, including failure to report full results, missing population details, multiple testing, and over-reliance on subgroup analysis. In summary, the complex phenotypes of OA and SDD may have made it difficult for researchers to focus their efforts. The field is dominated by isolated analyses of disparate potential associations, a problem that is amplified by the frequent analysis of different polymorphisms within individual genes. Flaws in study methodology and interpretation undoubtedly increase the risk of publication bias. Closer adherence to published recommendations (in particular those produced by HuGENet) will help to ensure that future studies are well-designed and build on current understanding, rather than simply adding to the growing bank of potential associations.

Dietary advice for treatment of type 2 diabetes mellitus in adults.

BACKGROUND: While initial dietary management immediately after formal diagnosis is an 'accepted' cornerstone of treatment of type 2 diabetes mellitus, a formal and systematic overview of its efficacy and method of delivery is not currently available. OBJECTIVES: To assess the effects of type and frequency of different types of dietary advice for adults with type 2 diabetes. SEARCH STRATEGY: We carried out a comprehensive search of The Cochrane Library, MEDLINE, EMBASE, CINAHL, AMED, bibliographies and contacted relevant experts. SELECTION CRITERIA: All randomised controlled trials, of six months or longer, in which dietary advice was the main intervention. DATA COLLECTION AND ANALYSIS: The lead investigator performed all data extraction and quality scoring with duplication being carried out by one of the other six investigators independently with discrepancies resolved by discussion and consensus. Authors were contacted for missing data. MAIN RESULTS: Thirty-six articles reporting a total of eighteen trials following 1467 participants were included. Dietary approaches assessed in this review were low-fat/high-carbohydrate diets, high-fat/low-carbohydrate diets, low-calorie (1000 kcal per day) and very-low-calorie (500 kcal per day) diets and modified fat diets. Two trials compared the American Diabetes Association exchange diet with a standard reduced fat diet and five studies assessed low-fat diets versus moderate fat or low-carbohydrate diets. Two studies assessed the effect of a very-low-calorie diet versus a low-calorie diet. Six studies compared dietary advice with dietary advice plus exercise and three other studies assessed dietary advice versus dietary advice plus behavioural approaches. The studies all measured weight and measures of glycaemic control although not all studies reported these in the articles published. Other outcomes which were measured in these studies included mortality, blood pressure, serum cholesterol (including LDL and HDL cholesterol), serum triglycerides, maximal exercise capacity and compliance. The results suggest that adoption of regular exercise is a good way to promote better glycaemic control in type 2 diabetic patients, however all of these studies were at high risk of bias. AUTHORS' CONCLUSIONS: There are no high quality data on the efficacy of the dietary treatment of type 2 diabetes, however the data available indicate that the adoption of exercise appears to improve glycated haemoglobin at six and twelve months in people with type 2 diabetes. There is an urgent need for well-designed studies which examine a range of interventions, at various points during follow-up, although there is a promising study currently underway.

Paracetamol for pain relief after surgical removal of lower wisdom teeth.

BACKGROUND: Paracetamol has been commonly used for the relief of postoperative pain following oral surgery. In this review we investigated the optimal dose of paracetamol and the optimal time for drug administration to provide pain relief, taking into account the side effects of different doses of the drug. This will inform dentists and their patients of the best strategy for pain relief after the surgical removal of wisdom teeth. OBJECTIVES: To assess the beneficial and harmful effects of paracetamol for pain relief after surgical removal of lower wisdom teeth, compared to placebo, at different doses and administered postoperatively. SEARCH STRATEGY: We searched the Cochrane Oral Health Group's Trials Register; the Cochrane Pain, Palliative and Supportive Care Group's Trials Register; CENTRAL; MEDLINE; EMBASE and the Current Controlled Trials Register. Handsearching included several dental journals. We checked the bibliographies of relevant clinical trials and review articles for studies outside the handsearched journals. We wrote to authors of the identified randomised controlled trials (RCTs), to manufacturers of analgesic pharmaceuticals, we searched personal references in an attempt to identify unpublished or ongoing RCTs. No language restriction was applied. The last electronic search was conducted on 24th August 2006. SELECTION CRITERIA: Randomised, parallel group, placebo controlled, double blind clinical trials of paracetamol for acute pain, following third molar surgery. DATA COLLECTION AND ANALYSIS: All trials identified were scanned independently and in duplicate by two review authors, any disagreements were resolved by discussion, or if necessary a third review author was consulted. The proportion of patients with at least 50% pain relief was calculated for both paracetamol and placebo. The number of patients experiencing adverse events, and/or the total number of adverse events reported were analysed. MAIN RESULTS: Twenty-one trials met the inclusion criteria. A total of 2048 patients were initially enrolled in the trials (1148 received paracetamol, and 892 the placebo) and of these 1968 (96%) were included in the meta-analysis (1133 received paracetamol, and 835 the placebo). Paracetamol provided a statistically significant benefit when compared with placebo for pain relief and pain intensity at both 4 and 6 hours. Most studies were found to have moderate risk of bias, with poorly reported allocation concealment being the main problem. Risk ratio values for pain relief at 4 hours 2.85 (95% confidence interval (CI) 1.89 to 4.29), and at 6 hours 3.32 (95% CI 1.88 to 5.87). A statistically significant benefit was also found between up to 1000 mg and 1000 mg doses, the higher the dose giving greater benefit for each measure at both time points. There was no statistically significant difference between the number of patients who reported adverse events, overall this being 19% in the paracetamol group and 16% in the placebo group. AUTHORS' CONCLUSIONS: Paracetamol is a safe, effective drug for the treatment of postoperative pain following the surgical removal of lower wisdom teeth.

Interferon-beta and adhesion molecules (E-selectin and s-intracellular adhesion molecule-1) are detected in sera from patients with retinal vasculitis and are induced in retinal vascular endothelial cells by Toll-like receptor 3 signalling.

Retinal vasculitis is a major component of ocular inflammation that plays a role in retinal tissue damage in patients with idiopathic uveitis and Behçet's disease. Here we show that type 1 interferons (IFN alpha/beta) were not detected in sera from normal individuals but were identified in up to 46% of the sera from retinal vasculitis patients. The predominant form of IFN observed was IFN-beta, which was detected in 39% of Behçet's disease patients and 47% of idiopathic uveitis patients. Seven patients whose sera contained IFN-beta were monitored prospectively. IFN-beta was shown to be present for 6-12 months in all seven of the sera samples tested. Furthermore, the adhesion molecule profile identified in this study was strikingly different when Behçet's and uveitis patient sera were compared to sera from normal controls. Sera from Behçet's disease patients contained significantly elevated levels of the soluble adhesion molecules, sE-selectin and s-intracellular adhesion molecule-1 (sICAM-1), whereas sera from patients with idiopathic uveitis contained significantly increased sE-selectin. In vitro studies evaluating the cell source of these cytokines revealed that polyriboinosinic polyribocytidylic acid (poly I:C) activated retinal vascular endothelial cells produce sE-selectin, sICAM-1 and IFN-beta. Production of these molecules was inhibited by pretreatment with anti-Toll-like receptor 3 (TLR-3) antibody. In conclusion, IFN-beta, sE-selectin and sICAM-1 are elevated in patients with retinal vasculitis and are induced in retinal vascular endothelial cells in vitro by activating the innate immune system through TLR-3. Further analysis of innate immune signalling may prove to be a novel target for future studies on pathogenic mechanisms and therapeutic approaches in retinal vasculitis.

Dietetic guidelines on food and nutrition in the secondary prevention of cardiovascular disease - evidence from systematic reviews of randomized controlled trials (second update, January 2006).

AIM: To update dietetic guidelines based on systematic review evidence on dietary advice to prevent further events in people with existing cardiovascular disease (CVD) (secondary prevention). METHODS: The Cochrane Library, MEDLINE and EMBASE were comprehensively searched to January 2005 for systematic reviews on aspects of diet and heart health. Reviews were included if they searched systematically for randomized controlled trials relating to diet and secondary prevention of CVD. Each review was critically appraised by at least two members of the UK Heart Health and Thoracic Dietitians Group. The quality and results of each review were discussed and summarized at a group meeting. RESULTS: Evidence-based strategies that reduce cardiovascular events in those with CVD include reduction in saturated fat and substitution with unsaturated fats. Individuals who have suffered a myocardial infarction may also benefit from adopting a Mediterranean type diet and increasing intake of omega 3 fats, but it is not clear whether they are beneficial for all patients with CVD. There is no systematic review evidence to support the use of antioxidant vitamins supplements, low glycaemic index diets, or homocysteine lowering therapies in this group. CONCLUSION: There remains good evidence that reducing saturated fat reduces morbidity in patients with CVD. This advice is consistent for most manifestations of CVD, with the addition of Mediterranean dietary advice and increased omega 3 fats for those who have had a myocardial infarction.

A comparison of the cost-effectiveness of five strategies for the prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal toxicity: a systematic review with economic modelling.

OBJECTIVES: To assess the relative effectiveness, patient acceptability, costs and cost-effectiveness of four strategies for the prevention of non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastrointestinal (GI) toxicity: (1) Cox-1 NSAIDs plus histamine-2 receptor antagonist (H2RA), (2) Cox-1 NSAIDs plus proton pump inhibitors (PPIs), (3) Cox-1 NSAIDs plus misoprostol, and (4) Cox-2 NSAIDs (later expanded to 4a Cox-2 coxibNSAIDs and 4b Cox-2 preferential NSAIDs). DATA SOURCES: Electronic databases up to May 2002. REVIEW METHODS: Relevant studies were selected, assessed and analysed. Pooled relative risk ratios (RR) from the systematic review were combined with up-to-date UK resource use and unit costs data in an incremental economic analysis. A probabilistic decision-analytic model was designed and populated with data to carry out incremental economic analysis. Incremental cost-effectiveness ratios (ICERs) were generated for the outcome measure, endoscopic ulcer or serious GI event averted, against total cost, and non-parametric bootstrapping was used to simulate variance of these ICERs. RESULTS: Of 118 selected trials, including 125 relevant comparisons (which included 76,322 participants) only 138 deaths and 248 serious GI events were reported. Seven comparisons were judged to be at low risk of bias. Comparing the gastroprotective strategies against placebo, there was no evidence of effectiveness of H2RAs against any primary outcomes (few events reported), PPIs may reduce the risk of symptomatic ulcers [RR 0.09, 95% confidence interval (CI) 0.02 to 0.47], misoprostol reduces the risk of serious GI complications (RR 0.57, 95% CI 0.36 to 0.91) and symptomatic ulcers (RR 0.36, 95% CI 0.20 to 0.67), Cox-2 'preferentials' reduce the risk of symptomatic ulcers (RR 0.41, 95% CI 0.26 to 0.65) and Cox-2 'coxibs' reduce the risk of symptomatic ulcers (RR 0.49, 95% CI 0.38 to 0.62) and possibly serious GI events (RR 0.55, 95% CI 0.38 to 0.80). All strategies except Cox-2 'preferentials' reduce the risk of endoscopic ulcers. There were only 12 direct comparisons between gastroprotective strategies. All they suggest is that Cox-2 preferentials are better than misoprostol for preventing GI complications. Indirect comparisons suggested that PPIs may prevent symptomatic ulcers better than Cox-2 coxibs, but this is very weak evidence. For prevention of endoscopic ulcers PPIs and misoprostol appear more successful than H2RAs and misoprostol is better than Cox-2 preferentials. There were no UK head-to-head published economic analyses with regard to the main gastroprotective strategies. There were generally insufficient data with regards to cardiac or renal outcomes, serious GI outcomes or life-years gained to populate the mode. Mean (2.5th and 97.5th percentile) costs per endoscopic ulcer averted compared with Cox-1 NSAIDs alone were as follows: Cox-1 plus H2RAs, -186 pounds (-555 to 804); Cox-1 plus PPIs, 454 pounds (251 to 877); Cox-1 plus misoprostol, 54 pounds (-112 to 238); Cox-2 selective NSAIDs, 263 pounds (-570 to 1280), or Cox-2 specific NSAIDs, 301 pounds (189 to 418). With regard to the prevention of endoscopic ulcers, Cox-1 NSAID plus H2RA is a dominant option. Cost-effectiveness acceptability analysis showed a 95% probability that this combination was less costly and more effective. Cost-effectiveness acceptability frontiers showed that if the decision-maker is willing to pay up to 750 pounds to avoid an endoscopic ulcer, then Cox-1 plus H2RA is the optimal strategy. If the decision-maker is willing to pay over 750 pounds, the optimal strategy is NSAID plus misoprostol. Between 1900 pounds and 3750 pounds, Cox-2 selective inhibitors are optimal, and over 3750 pounds, Cox-2 specific inhibitors become optimal. NSAID plus PPI is never the optimal strategy. Sensitivity and subgroup analyses suggest that Cox-1 NSAID plus H2RA and Cox-1 NSAID plus misoprostol become more cost-effective in the older age group. Some conclusions were associated with high levels of uncertainty. CONCLUSIONS: Although there is a very large body of evidence comparing Cox-2 NSAIDs with Cox-1 NSAIDs, this is not matched by studies of the other types of gastroprotectors or by studies directly comparing active gastroprotective strategies. This lack of direct comparisons led to the use of indirect comparisons to help understand the relative efficacy of these strategies. Indirect evidence in itself is weak and was also hampered by lack of evidence in the underlying studies (where the gastroprotectors were compared with placebo). Economic modelling suggests that Cox-1 NSAID plus H2RA or Cox-1 NSAID plus PPI are the most cost-effective strategies for avoiding endoscopic ulcers in patients requiring long-term NSAID therapy. All strategies other than Cox-2 selective inhibitors reduce the rate of endoscopic ulcer compared with Cox-1 alone. The economic analysis suggests that there may be a case for prescribing H2RAs in all patients requiring NSAIDs. Misoprostol is more effective, but is associated with a greater cost and GI side-effects which may be unacceptable for patients. However, when assessing serious GI events, the economic analysis is sufficiently weakened by the data available as to render clear practice recommendations impossible. Further large, independent RCTs directly comparing various gastroprotective strategies are needed. These should report items such as major outcomes, primary data, adverse events, assessment of practice and patient preference.

The SDF-1 G > A polymorphism at position 801 plays no role in multiple myeloma but may contribute to an inferior cause-specific survival in chronic lymphocytic leukemia.

The growth and circulation of B lymphocytes is largely under the control of bone marrow stromal cells, cytokines and chemokines. The gene responsible for the pivotal B cell growth factor, stromal derived factor-1 (SDF-1), has recently been shown to contain a single nucleotide polymorphism G > A at position 801 which leads to higher SDF-1 secretion. This polymorphism is common in the normal population and has been shown to play a potential role in the development of both HIV and non-HIV related non-Hodgkin's lymphoma. We therefore undertook a large single-centre study to ascertain its role in the pathogenesis of two other common B-cell malignancies, notably chronic lymphocytic leukemia (CLL- 197 patients) and multiple myeloma (126 patients). We show that the 801 G > A polymorphism plays no role in the incidence of multiple myeloma or CLL nor the outcome in multiple myeloma. By contrast, it trends towards an inferior cause-specific survival in CLL.