Publication bias in the medical literature: A review by a Canadian research ethics board

BACKGROUND: We reviewed the publication record of all protocols submitted to the Capital District Health Authority Research Ethics Board (REB) in Halifax, Nova Scotia, for the period 1995-1996. Because of a heightened awareness of the issue, we hypothesized that there would be less publication bias (a failure to report negative results) and a higher publication rate from completed studies, than previously reported. METHODS: Closed studies were identified from the REB database. Publications were identified by the investigators, requests from sponsors, and a literature review. For each publication, we identified authors, title, journal, number of subjects enrolled, and whether or not the publication was a report of a randomized clinical trial. Comparisons were done using a Student's t test, the Chi-square statistic, or Fisher's exact test as appropriate. RESULTS: From the database of closed studies, 106 remained unpublished, while completed investigations resulted in 84 publications (44% publication rate). The median time to publication was 32.5 months. Publication of statistically significant results occurred in 71/84 trials. Publication of protocols submitted by departments ranged from 91% (anesthesia; 10/11) to 25% [nursing; 2/8 (P<0.05)]. Trials investigating new drugs in Phase 3 or 4 studies were more likely to be published than trials investigating agents in Phase 1 or 2 (P<0.05), and were less likely to be published if sponsored by a pharmaceutical company (P<0.05). CONCLUSIONS: Publication bias continues to be a problem, particularly for early phase investigative studies. Our results suggest that a different approach is required to reduce publication bias. The role that REBs and peer-reviewed journals might play requires further exploration.     

The validity of a separate classification of cryptogenic localization related epilepsy amongst childhood epilepsies.

INTRODUCTION: One-third of children with epilepsy are classified as having a cryptogenic localization related epilepsy (CLRE). In cohort studies CLRE is often grouped together with either symptomatic localization related epilepsy (SLRE) or idiopathic generalized epilepsy (IGE). Therefore, this categorization is not specific enough and will not lead to prognostic or treatment information. We objectified the classification differences between these categories. METHODS: A total of 114 children admitted to our epilepsy centre underwent a standardized clinical analysis, which yielded age at onset, duration of the epilepsy, seizure frequency, seizure type, percentage of interictal epileptiform activity on EEG (IEA), type of treatment, and full scale IQ. These variables are regarded the characteristics of the epilepsy, and used in a discriminant function analysis. RESULTS: IEA was found to be the only variable to distinguish between groups of epilepsy. SLRE could easily be distinguished significantly from IGE and CLRE, while the latter two did not differ significantly. Discriminant function analysis combined the variables into two functions, applicable to classify the children. By applying this statistical analysis method, the groups clinically classified as SLRE and IGE were mostly classified as SLRE (71.4%) and IGE (57.9%). However, CLRE appeared difficult to classify (49.2%), and most children were classified as either SLRE (19%) or IGE (31.7%). CONCLUSION: The current opinion that CLRE is 'probably symptomatic' cannot be confirmed in all cases in this study. It is most likely that the current CLRE population consists of both children with eventually SLRE, as well as yet to be described syndromes to be classified as idiopathic epilepsies. We emphasize the need for separate studies regarding children with 'probably symptomatic' (cryptogenic) localization related epilepsy, as this will maximally help children, caretakers and treating physicians to achieve the best possible outcome.     

Sural nerve biopsies in Guillain-Barre syndrome: axonal degeneration and macrophage-associated demyelination and absence of cytomegalovirus genome.

T-cell infiltration was detected by immunohistochemistry in only 2 of 10 sural nerve biopsies from patients with Guillain-Barré syndrome (GBS). The number of endoneurial macrophages, identified by the monoclonal antibody MAC 387, was increased, compared with the number in 10 cases of axonal neuropathy. Macrophage-associated demyelination was identified in 7 and axonal degeneration in 8 cases. Cytomegalovirus (CMV) genome was not detected with the polymerase chain reaction.     

Early Stroke Recognition: Developing an Out-of-hospital NIH Stroke Scale

Objective : To develop an abbreviated and practical neurologic scale that could assist emergency medical services or triage personnel in identifying patients with stroke.
Methods : A prospective, observational, cohort study was performed at university-based EDs. Participants were 74 patients treated in a thrombolytic stroke trial and 225 consecutive non-stroke patients evaluated during 4 random 12-hour shifts in the ED. Scores on the NIH Stroke Scale were obtained for all patients by physicians. Items of this scale were modified and recoded to a binomial (normal or abnormal) scale. Serial univariate analyses using χ² were performed to rank items. Recursive partitioning was then performed to develop the decision rule for predicting the presence of stroke.
Results : Three items identified 100% of patients with stroke: facial palsy, motor arm, and dysarthria. An Abbreviated NIH Stroke Scale based on these items had a sensitivity of 100% and a specificity of 92%. A proposed Out-of-hospital NIH Stroke Scale consisting of facial palsy, motor arm, and a combination of dysarthria and best language items (abnormal speech) had a sensitivity of 100% and a specificity of 88%.
Conclusion : Using the derivation data set, a proposed Out-of-hospital NIH Stroke Scale had a high sensitivity and specificity for identifying patients with stroke when performed by physicians in this group of 299 ED patients. Prospective studies of other health care professionals using the scale in the out-of-hospital arena are needed.     

ISCHAEMIA-REPERFUSION INJURY TO THE INTESTINE

Ischaemia-reperfusion injury (IRI) is of obvious relevance in situations where there is an interruption of blood supply to the gut, as in vascular surgery, or in the construction of free intestinal grafts. It is now appreciated that IRI also underlies the gut dysfunction that occurs in early shock, sepsis, and trauma. The events that occur during IRI are complex. However, recent advances in cellular biology have started to unravel these underlying processes. The aim of this review is to provide an outline of current knowledge on the mechanisms and consequences of IRI. Initially, IRI appears to be mediated by reactive oxygen metabolites and, at a later stage, by the priming and activation of polymorphonuclear neutrophils (PMN). Ischaemia-reperfusion injury can diminish the barrier function of the gut, and can promote an increase in the leakage of molecules (intestinal permeability) or the passage of microbes across the wall of the bowel (bacterial trans-location). Ischaemia-reperfusion injury to the gut can result in the generation of molecules that may also harm distant tissues.