Systematic review of dexketoprofen in acute and chronic pain

Background: Dexketoprofen, and NSAID used in the management of acute and chronic pains, is licensed in several countries but has not previously been the subject 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 We used published and unpublished information from randomised clinical trials (RCTs) of dexketoprofen in painful conditions to assess evidence on efficacy and harm.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 Menarini Group produced copies of published and unpublished studies (clinical trial reports).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 does 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 Information from 16 trials (almost half the total patients) was obtained from clinical trial reports from previously unpublished trials or abstracts. Almost all of the trials were of short duration in acute conditions or recent onset pain. All 12 randomised trials that compared dexketoprofen (any dose) with placebo found dexketoprofen to be statistically superior. Five trials in postoperative pain yielded NNTs for 12.5 mg dexketoprofen of 3.5 (2.7 to 4.9), 25 mg dexketoprofen of 3.0 (2.4 to 3.9), and 50 mg dexketoprofen of 2.1 (1.5 to 3.5). In 29/30 active comparator trials, dexketoprofen at the dose used was at least equivalent in efficacy to comparator drugs. Adverse event withdrawal rates were low in postoperative pain and somewhat higher in trials of longer duration; no serious adverse events were reported. Conclusion: Dexketoprofen was at least as effective as other NSAIDs and paracetamol/opioid combinations. While adverse event withdrawal was not different between dexketoprofen and comparator analgesics, the different conditions and comparators studies precluded any formal analysis. Exposure was limited, and no conclusions could be drawn about safety in terms of serious adverse events like gastrointestinal bleeding or cardiovascular events

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 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

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 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

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

2022 World Hypertension League, Resolve To Save Lives and International Society of Hypertension dietary sodium (salt) global call to action

This fact sheet and global call to action is aimed at nutrition, hypertension, cardiovascular and other health care clinicians and scientists, and health advocates, as well as the organizations to which they belong. The ‘call’ is to align these audiences with the facts on: the burden of disease and key evidence supporting reductions in dietary sodium, the consistent recommendations for reducing dietary sodium from unbiased and comprehensive health and scientific reviews, the current levels of sodium intake, the cost savings expected from reducing high dietary sodium, the sources of controversial opinions, the current recommended approaches to reduce dietary sodium, and how to stay up to date with evidence on how to reduce dietary sodium and the evolving research on the adverse health effects of a high sodium intake. Health, nutrition, hypertension and cardiovascular organizations, and their members, need to become more engaged and advocate for reductions in dietary sodium, and for a greater priority to be given to high quality research on dietary sodium. The World Hypertension League, Resolve to Save Lives and International Society of Hypertension are committed to support reductions in dietary sodium as a high priority