Multicentre observational cohort study of NSAIDs as risk factors for postoperative adverse events in gastrointestinal surgery

Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as postoperative analgesia by the Enhanced Recovery After Surgery Society. Recent studies have raised concerns that NSAID administration following colorectal anastomosis may be associated with increased risk of anastomotic leak. This multicentre study aims to determine NSAIDs' safety profile following gastrointestinal resection. Methods and analysis: This prospective, multicentre cohort study will be performed over a 2-week period utilising a collaborative methodology. Consecutive adults undergoing open or laparoscopic, elective or emergency gastrointestinal resection will be included. The primary end point will be the 30-day morbidity, assessed using the Clavien-Dindo classification. This study will be disseminated through medical student networks, with an anticipated recruitment of at least 900 patients. The study will be powered to detect a 10% increase in complication rates with NSAID use. Ethics and dissemination: Following the Research Ethics Committee Chairperson's review, a formal waiver was received. This study will be registered as a clinical audit or service evaluation at each participating hospital. Dissemination will take place through previously described novel research collaborative networks

Zinc Acetate Lozenges May Improve the Recovery Rate of Common Cold Patients : An Individual Patient Data Meta-Analysis

BACKGROUND: A previous meta-analysis of 3 zinc acetate lozenge trials estimated that colds were on average 40% shorter for the zinc groups. However, the duration of colds is a time outcome, and survival analysis may be a more informative approach. The objective of this individual patient data (IPD) meta-analysis was to estimate the effect of zinc acetate lozenges on the rate of recovery from colds. METHODS: We analyzed IPD for 3 randomized placebo-controlled trials in which 80-92 mg/day of elemental zinc were administered as zinc acetate lozenges to 199 common cold patients. We used mixed-effects Cox regression to estimate the effect of zinc. RESULTS: Patients administered zinc lozenges recovered faster by rate ratio 3.1 (95% confidence interval, 2.1-4.7). The effect was not modified by age, sex, race, allergy, smoking, or baseline common cold severity. On the 5th day, 70% of the zinc patients had recovered compared with 27% of the placebo patients. Accordingly, 2.6 times more patients were cured in the zinc group. The difference also corresponds to the number needed to treat of 2.3 on the 5th day. None of the studies observed serious adverse effects of zinc. CONCLUSIONS: The 3-fold increase in the rate of recovery from the common cold is a clinically important effect. The optimal formulation of zinc lozenges and an ideal frequency of their administration should be examined. Given the evidence of efficacy, common cold patients may be instructed to try zinc acetate lozenges within 24 hours of onset of symptoms.Peer reviewe

Zinc acetate lozenges for treating the common cold : an individual patient data meta-analysis

AimsThe aim of this study was to determine whether the allergy status and other characteristics of common cold patients modify the effects of zinc acetate lozenges. MethodsWe had available individual patient data for three randomized placebo-controlled trials in which zinc acetate lozenges were administered to common cold patients. We used both one stage and two stage meta-analysis to estimate the effects of zinc lozenges. ResultsThe total number of common cold patients was 199, the majority being females. Eighty percent of them fell into the age range 20-50years. One third of the patients had allergies. The one stage meta-analysis gave an overall estimate of 2.73days (95% CI 1.8, 3.3days) shorter colds by zinc acetate lozenge usage. The two stage meta-analysis gave an estimate of 2.94days (95% CI 2.1, 3.8days) reduction in common cold duration. These estimates are to be compared with the 7day average duration of colds in the three trials. The effect of zinc lozenges was not modified by allergy status, smoking, baseline severity of the common cold, age, gender or ethnic group. ConclusionSince the effects of zinc acetate lozenges were consistent between the compared subgroups, the overall estimates for effect seemed applicable over a wide range of common cold patients. While the optimal composition of zinc lozenges and the best frequency of their administration should be further investigated, given the current evidence of efficacy, common cold patients may be encouraged to try zinc lozenges for treating their colds.Peer reviewe

Less Than Full-time Training in surgical specialities: Consensus recommendations for flexible training by the Association of Surgeons in Training

AbstractChanges in lifestyle, career expectations, and working environments, alongside the feminisation of the workforce have resulted in an increased demand for Less Than Full-time Training (LTFT) within surgery. However, provision of and adequacy of flexible training remain variable. It is important that LTFT options are provided to ensure surgery is an attractive and viable career option, and can compete with other specialties to attract and retain the best candidates to maintain high standards of patient care. LTFT options should be readily available to both genders within surgical specialities. Furthermore, improved information for those considering LTFT should be available, locally, regionally and nationally. Training within LTFT posts should be tailored to the training requirements of the individual, in order to achieve the competencies necessary for completion of training. The recommendations set out in this consensus statement should inform the trainee's position and help guide discussions with respect to the provision of LTFT within surgery

Correcting for the Effects of Interstellar Extinction

This paper addresses the issue of how best to correct astronomical data for the wavelength-dependent effects of Galactic interstellar extinction. The main general features of extinction from the IR through the UV are reviewed, along with the nature of observed spatial variations. The enormous range of extinction properties found in the Galaxy, particularly in the UV spectral region, is illustrated. Fortunately, there are some tight constraints on the wavelength dependence of extinction and some general correlations between extinction curve shape and interstellar environment. These relationships provide some guidance for correcting data for the effects of extinction. Several strategies for dereddening are discussed along with estimates of the uncertainties inherent in each method. In the Appendix, a new derivation of the wavelength dependence of an average Galactic extinction curve from the IR through the UV is presented, along with a new estimate of how this extinction law varies with the parameter R = A(V)/E(B-V). These curves represent the true monochromatic wavelength dependence of extinction and, as such, are suitable for dereddening IR--UV spectrophotometric data of any resolution, and can be used to derive extinction relations for any photometry system.Comment: To appear in PASP (January 1999) 14 pages including 4 pages of figures Uses emulateapj style. PASP, in press (January 1999

Carcinogenicity studies in rodents with ripazepam, a minor tranquilizing agent

The carcinogenesis potential of ripazepam, a benzodiazepine derivative, was studied in mice and rats for 78 and 104 weeks, respectively. Groups of 50 male and 50 female CD1 mice and CD rats each were given doses of 15 and 150 mg/kg of ripazepam in the diet. Survival rates were adequate for statistical analysis. Significant suppression of body weight gains occurred in rats but not in mice given 150 mg/kg/day. The compound failed to increase tumor rates or alter the average latency of neoplasms in the rat. In mice, the number of male animals with tumors was increased at 150 mg/kg and this was related to a significant increase in the number of animals with hepatocellular tumors. Hepatocellular tumors were increased also in female mice but the increase was not statistically significant. All but one of these hepatic neoplasms were hepatocellular adenomas and the one carcinoma had not metastasized. Other tumor types were not increased.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24852/1/0000279.pd

Discontinuation and non-publication of surgical randomised controlled trials:observational study

Objective To determine the rate of early discontinuation and non-publication of randomised controlled trials involving patients undergoing surgery. Design Cross sectional observational study of registered and published trials. Setting Randomised controlled trials of interventions in patients undergoing a surgical procedure. Data sources The ClinicalTrials.gov database was searched for interventional trials registered between January 2008 and December 2009 using the keyword “surgery”. Recruitment status was extracted from the ClinicalTrials.gov database. A systematic search for studies published in peer reviewed journals was performed; if they were not found, results posted on the ClinicalTrials.gov results database were sought. Email queries were sent to trial investigators of discontinued and unpublished completed trials if no reason for the respective status was disclosed. Main outcome measures Trial discontinuation before completion and non-publication after completion. Logistic regression was used to determine the effect of funding source on publication status, with adjustment for intervention type and trial size. Results Of 818 registered trials found using the keyword “surgery”, 395 met the inclusion criteria. Of these, 21% (81/395) were discontinued early, most commonly owing to poor recruitment (44%, 36/81). The remaining 314 (79%) trials proceeded to completion, with a publication rate of 66% (208/314) at a median time of 4.9 (interquartile range 4.0-6.0) years from study completion to publication search. A further 6% (20/314) of studies presented results on ClinicalTrials.gov without a corresponding peer reviewed publication. Industry funding did not affect the rate of discontinuation (adjusted odds ratio 0.91, 95% confidence interval 0.54 to 1.55) but was associated with a lower odds of publication for completed trials (0.43, 0.26 to 0.72). Investigators’ email addresses for trials with an uncertain fate were identified for 71.4% (10/14) of discontinued trials and 83% (101/122) of unpublished studies. Only 43% (6/14) and 20% (25/122) replies were received. Email responses for completed trials indicated 11 trials in press, five published studies (four in non-indexed peer reviewed journals), and nine trials remaining unpublished. Conclusions One in five surgical randomised controlled trials are discontinued early, one in three completed trials remain unpublished, and investigators of unpublished studies are frequently not contactable. This represents a waste of research resources and raises ethical concerns regarding hidden clinical data and futile participation by patients with its attendant risks. To promote future efficiency and transparency, changes are proposed to research governance frameworks to overcome these concerns