Copper Chaperone for Cu/Zn Superoxide Dismutase is a sensitive biomarker of mild copper deficiency induced by moderately high intakes of zinc

BACKGROUND: Small increases in zinc (Zn) consumption above recommended amounts have been shown to reduce copper (Cu) status in experimental animals and humans. Recently, we have reported that copper chaperone for Cu/Zn superoxide dismutase (CCS) protein level is increased in tissues of overtly Cu-deficient rats and proposed CCS as a novel biomarker of Cu status. METHODS: Weanling male Wistar rats were fed one of four diets normal in Cu and containing normal (30 mg Zn/kg diet) or moderately high (60, 120 or 240 mg Zn/kg diet) amounts of Zn for 5 weeks. To begin to examine the clinical relevance of CCS, we compared the sensitivity of CCS to mild Cu deficiency, induced by moderately high intakes of Zn, with conventional indices of Cu status. RESULTS: Liver and erythrocyte CCS expression was significantly (P < 0.05) increased in rats fed the Zn-60 and/or Zn-120 diet compared to rats fed normal levels of Zn (Zn-30). Erythrocyte CCS expression was the most sensitive measure of reduced Cu status and was able to detect a decrease in Cu nutriture in rats fed only twice the recommended amount of Zn. Liver, erythrocyte and white blood cell CCS expression showed a significant (P < 0.05) inverse correlation with plasma and liver Cu concentrations and caeruloplasmin activity. Unexpectedly, rats fed the highest level of Zn (Zn-240) showed overall better Cu status than rats fed a lower level of elevated Zn (Zn-120). Improved Cu status in these rats correlated with increased duodenal mRNA expression of several Zn-trafficking proteins (i.e. MT-1, ZnT-1, ZnT-2 and ZnT-4). CONCLUSION: Collectively, these data show that CCS is a sensitive measure of Zn-induced mild Cu deficiency and demonstrate a dose-dependent biphasic response for reduced Cu status by moderately high intakes of Zn

Single- versus two- layer intestinal anastomosis: a meta-analysis of randomized controlled trials

BACKGROUND: To compare single- with two- layer intestinal anastomosis after intestinal resection: a meta-analysis of randomized controlled trials. METHODS: Randomized controlled trials comparing single- with two-layer intestinal anastomosis were identified using a systematic search of Medline, Embase and the Cochrane Library Databases covering articles published from 1966 to 2004. Outcome of primary interest was postoperative leak. A risk ratio for trial outcomes and weighted pooled estimates for data were calculated. A fixed-effect model weighted using Mantel-Haenszel methods and a random-effect model using DerSimonian-Laird methods were employed. RESULTS: Six trials were analyzed, comprising 670 participants (single-layer group, n = 299; two-layer group, n = 371). Data on leaks were available from all included studies. Combined risk ratio using DerSimonian-Laird methods was 0.91 (95% CI = 0.49 to 1.69), and indicated no significant difference. Inter-study heterogeneity was significant (χ(2 )= 10.5, d.f. = 5, p = 0.06). CONCLUSION: No evidence was found that two-layer intestinal anastomosis leads to fewer post-operative leaks than single layer. Considering duration of the anastomosis procedure and medical expenses, single-layer intestinal anastomosis appears to represent the optimal choice for most surgical situations

Attributable mortality to radon exposure in Galicia, Spain. Is it necessary to act in the face of this health problem?

<p>Abstract</p> <p>Background</p> <p>Radon is the second risk factor for lung cancer after tobacco consumption and therefore it is necessary to know the burden of disease due to its exposure. The objective of this study is to estimate radon-attributable lung cancer mortality in Galicia, a high emission area located at the Northwest Spain.</p> <p>Methods</p> <p>A prevalence-based attribution method was applied. Prevalence of tobacco use and radon exposure were obtained from a previously published study of the same area. Attributable mortality was calculated for each of six possible risk categories, based on radon exposure and smoking status. Two scenarios were used, with 37 Bq/m³and 148 Bq/m³as the respective radon exposure thresholds. As the observed mortality we used lung cancer mortality for 2001 from the Galician mortality registry.</p> <p>Results</p> <p>Mortality exclusively attributable to radon exposure ranged from 3% to 5% for both exposure thresholds, respectively. Attributable mortality to combined exposure to radon and smoking stood at around 22% for exposures above 148 Bq/m³. Applying the United States Environmental Protection Agency (EPA) action level, radon has a role in 25% of all lung cancers.</p> <p>Conclusions</p> <p>Although the estimates have been derived from a study with a relatively limited sample size, these results highlight the importance of radon exposure as a cause of lung cancer and its effect in terms of disease burden. Radon mitigation activities in the study area must therefore be enforced.</p

Meta-analysis: Neither quick nor easy

BACKGROUND: Meta-analysis is often considered to be a simple way to summarize the existing literature. In this paper we describe how a meta-analysis resembles a conventional study, requiring a written protocol with design elements that parallel those of a record review. METHODS: The paper provides a structure for creating a meta-analysis protocol. Some guidelines for measurement of the quality of papers are given. A brief overview of statistical considerations is included. Four papers are reviewed as examples. The examples generally followed the guidelines we specify in reporting the studies and results, but in some of the papers there was insufficient information on the meta-analysis process. CONCLUSIONS: Meta-analysis can be a very useful method to summarize data across many studies, but it requires careful thought, planning and implementation

Long acting β(2 )agonists for stable chronic obstructive pulmonary disease with poor reversibility: a systematic review of randomised controlled trials

BACKGROUND: The long acting β2-agonists, salmeterol and formoterol, have been recommended, by some, as first line treatment of stable chronic obstructive pulmonary disease (COPD). We reviewed evidence of efficacy and safety when compared with placebo or anticholinergic agents in patients with poorly reversible COPD. METHODS: After searching MEDLINE, EMBASE, HealthSTAR, BIOSIS Previews, PASCAL, ToxFile, SciSearch, the Cochrane Library, and PubMed, as well as Web sites, selected journals, reference lists, and contacting drug manufacturers, two reviewers independently screened reports of randomised controlled trials of parallel or crossover design lasting four weeks or longer and including patients with a forced expiratory volume in one second (FEV1) ≤ 75% of predicted, a ratio of FEV1 to forced vital capacity (FVC) ≤ 88% of predicted, and < 15% improvement from baseline FEV1 after a dose of a β2 agonist. We included trials comparing salmeterol or formoterol with placebo or with ipratropium bromide and reporting one of these outcomes: lung function; exercise capacity; quality of life scores; dyspnea; exacerbations; rescue inhaler use; incidence of tachycardia, hypokalemia, or dry mouth. Two reviewers assessed the quality of included reports using the Jadad scale and allocation concealment, and abstracted data. RESULTS: Twelve trials satisfied our inclusion criteria; eight were high quality (Jadad score >2) and four were low quality (≤ 2). The adequacy of allocation concealment was unclear in all of them. We did not perform a meta-analysis due to differences in trial design and how outcomes were reported. Two trials comparing salmeterol with ipratropium did not detect differences; one trial comparing formoterol and ipratropium described greater improvement with formoterol in morning PEFR (15.3 versus 7.1 l/min, p = 0.040). Of twelve trials comparing long acting β2 agonists with placebo, six reported no improvement in exercise capacity, eleven reported improvements in FEV1 lung function (one reported no improvement), six reported less rescue inhaler usage (one reported no difference) and five reported improved dyspnea scores (two reported no improvement). Differences in quality of life were detected in one salmeterol trial ; however, two salmeterol, and one formoterol trial reported no differences. Adverse effects of interest were not reported. CONCLUSION: In terms of clinical outcomes and safety, we could not find convincing evidence that salmeterol and formoterol have demonstrated advantages to ipratropium, a less expensive drug, for patients with stable COPD and poor reversibility. Compared to placebo, we found evidence of reduced rescue inhaler usage and improved spirometric outcomes without a significant impact on quality of life or exercise capacity

Topical NSAIDs for chronic musculoskeletal pain: systematic review and meta-analysis

A previous systematic review reported that topical NSAIDs were effective in relieving pain in chronic conditions like osteoarthritis and tendinitis. More trials, a better understanding of trial quality and bias, and a reclassification of certain drugs necessitate a new review. Studies were identified by searching electronic databases, and writing to manufacturers. We identified randomised, double blind trials comparing topical NSAID with either placebo or another active treatment, in adults with chronic pain. The primary outcome was a reduction in pain of approximately 50% at two weeks, and secondary outcomes were local and systemic adverse events and adverse event-related withdrawals. Relative benefit and number-needed-to-treat (NNT), and relative harm and number-needed-to-harm (NNH) were calculated, and the effects of trial quality, validity and size, outcome reported, and condition treated, were examined by sensitivity analyses. Twelve new trials were added to 13 trials from a previous review. Fourteen double blind placebo-controlled trials had information from almost 1,500 patients. Topical NSAID was significantly better than placebo with relative benefit 1.9 (95% confidence interval 1.7 to 2.2), NNT 4.6 (95% confidence interval 3.8 to 5.9). Results were not affected by trial quality, validity or size, outcome reported, or condition treated. Three trials with 764 patients comparing a topical with an oral NSAID found no difference in efficacy. Local adverse events (6%), systemic adverse events (3%), or the numbers withdrawing due to an adverse event were the same for topical NSAID and placebo. Topical NSAIDs were effective and safe in treating chronic musculoskeletal conditions for two weeks. Larger and longer trials are necessary to fully elucidate the place of topical NSAIDs in clinical practice

Are decision trees a feasible knowledge representation to guide extraction of critical information from randomized controlled trial reports?

<p>Abstract</p> <p>Background</p> <p>This paper proposes the use of decision trees as the basis for automatically extracting information from published randomized controlled trial (RCT) reports. An exploratory analysis of RCT abstracts is undertaken to investigate the feasibility of using decision trees as a semantic structure. Quality-of-paper measures are also examined.</p> <p>Methods</p> <p>A subset of 455 abstracts (randomly selected from a set of 7620 retrieved from Medline from 1998 – 2006) are examined for the quality of RCT reporting, the identifiability of RCTs from abstracts, and the completeness and complexity of RCT abstracts with respect to key decision tree elements. Abstracts were manually assigned to 6 sub-groups distinguishing whether they were primary RCTs versus other design types. For primary RCT studies, we analyzed and annotated the reporting of intervention comparison, population assignment and outcome values. To measure completeness, the frequencies by which complete intervention, population and outcome information are reported in abstracts were measured. A qualitative examination of the reporting language was conducted.</p> <p>Results</p> <p>Decision tree elements are manually identifiable in the majority of primary RCT abstracts. 73.8% of a random subset was primary studies with a single population assigned to two or more interventions. 68% of these primary RCT abstracts were structured. 63% contained pharmaceutical interventions. 84% reported the total number of study subjects. In a subset of 21 abstracts examined, 71% reported numerical outcome values.</p> <p>Conclusion</p> <p>The manual identifiability of decision tree elements in the abstract suggests that decision trees could be a suitable construct to guide machine summarisation of RCTs. The presence of decision tree elements could also act as an indicator for RCT report quality in terms of completeness and uniformity.</p

Topical NSAIDs for acute pain: a meta-analysis

BACKGROUND: A previous systematic review reported that topical NSAIDs were effective in relieving pain in acute conditions like sprains and strains, with differences between individual drugs for efficacy. More trials, a better understanding of trial quality and bias, and a reclassification of certain drugs necessitate a new review. METHODS: Studies were identified by searching electronic databases and writing to manufacturers. We selected randomised double blind trials comparing topical NSAID with either placebo or another active treatment in adults with acute pain, and extracted dichotomous information approximating to a 50% reduction in pain at one week, together with details of adverse events and withdrawals. Relative benefit and number-needed-to-treat (NNT), and relative risk and number-needed-to-harm (NNH) were calculated, with sensitivity analyses where appropriate to investigate differences between individual drugs and aspects of trial design. RESULTS: Twenty-six double blind placebo controlled trials had information from 2,853 patients for evaluation of efficacy. Topical NSAID was significantly better than placebo in 19 of the 26 trials, with a pooled relative benefit of 1.6 (95% confidence interval 1.4 to 1.7), and NNT of 3.8 (95% confidence interval 3.4 to 4.4) compared with placebo for the outcome of half pain relief at seven days. Results were not affected by outcome reported, or condition treated, but smaller trials yielded a larger estimate of efficacy. Indirect comparisons of individual topical NSAIDs showed that ketoprofen was significantly better than all other topical NSAIDs, while indomethacin was barely distinguished from placebo. Three trials, with 433 patients, compared topical with oral NSAID (two trials compared the same drug, one compared different drugs) and found no difference in efficacy. Local adverse events, systemic adverse events, or withdrawals due to an adverse event were rare, and no different between topical NSAID and placebo. CONCLUSIONS: Topical NSAIDs were effective and safe in treating acute painful conditions for one week

The use of preoperative radiotherapy in the management of patients with clinically resectable rectal cancer: a practice guideline

BACKGROUND: This systematic review with meta-analysis was designed to evaluate the literature and to develop recommendations regarding the use of preoperative radiotherapy in the management of patients with resectable rectal cancer. METHODS: The MEDLINE, CANCERLIT and Cochrane Library databases, and abstracts published in the annual proceedings of the American Society of Clinical Oncology and the American Society for Therapeutic Radiology and Oncology were systematically searched for evidence. Relevant reports were reviewed by four members of the Gastrointestinal Cancer Disease Site Group and the references from these reports were searched for additional trials. External review by Ontario practitioners was obtained through a mailed survey. Final approval of the practice guideline report was obtained from the Practice Guidelines Coordinating Committee. RESULTS: Two meta-analyses of preoperative radiotherapy versus surgery alone, nineteen trials that compared preoperative radiotherapy plus surgery to surgery alone, and five trials that compared preoperative radiotherapy to alternative treatments were obtained. Randomized trials demonstrate that preoperative radiotherapy followed by surgery is significantly more effective than surgery alone in preventing local recurrence in patients with resectable rectal cancer and it may also improve survival. A single trial, using surgery with total mesorectal excision, has shown similar benefits in local recurrence. CONCLUSION: For adult patients with clinically resectable rectal cancer we conclude that: • Preoperative radiotherapy is an acceptable alternative to the previous practice of postoperative radiotherapy for patients with stage II and III resectable rectal cancer; • Both preoperative and postoperative radiotherapy decrease local recurrence but neither improves survival as much as postoperative radiotherapy combined with chemotherapy. Therefore, if preoperative radiotherapy is used, chemotherapy should be added postoperatively to at least patients with stage III disease

Systematic review of dexketoprofen in acute and chronic pain

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Dexketoprofen, an NSAID used in the management of acute and chronic pains, is licensed in several countries but has not previously been the subjected of a systematic review. We used published and unpublished information from randomised clinical trials (RCTs) of dexketoprofen in painful conditions to assess evidence on efficacy and harm. Methods: PubMed and Cochrane Central were searched for RCTs of dexketoprofen for pain of any aetiology. Reference lists of retrieved articles and reviews were also searched. Menarini Group produced copies of published and unpublished studies (clinical trial reports). Data were abstracted into a standard form. For studies reporting results of single dose administration, the number of patients with at least 50 % pain relief was derived and used to calculate the relative benefit (RB) and number-needed-to-treat (NNT) for one patient to achieve at least 50 % pain relief compared with placebo. Results: Thirty-five trials were found in acute pain and chronic pain; 6,380 patients were included, 3,381 receiving dexketoprofen. Information from 16 trials (almost half the total patients) wa