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 RESULTS: From the database of closed studies, 106 remained unpublished, while completed investigations resulted in 84 publications (44% publication rate).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.     

Management of hepatocellular carcinoma presenting as obstructive jaundice

Eleven (3%) of 340 patients with hepatocellular carcinoma (HCC) presented with obstructive jaundice. The tumor extensively infiltrated the major bile ducts in eight patients. Jaundice was relieved by endoscopic endoprosthesis in four patients, nasobiliary drainage in two patients, percutaneous transhepatic stenting in one patient, and surgical intubation in one patient. The survival interval of these eight patients (mean +/- SD) was 35 +/- 20 days. Three patients had tumor fragments in the common bile ducts. In two patients, major hepatic resection was done after initial tube decomposition of the biliary system. One patient remained tumor-free on follow-up at 24 months, and the other patient had recurrent tumor detected on follow-up at 17 months after surgery. The tumor was irresectable in the third patient. Multiple surgical and endoscopic procedures kept the bile duct patent for 17 months before the patient died of the disease. Not all patients who present with obstructive jaundice due to HCC are terminally ill. With proper management, good palliation and occasional cure are possible.     

ELECTRICAL REMODELLING OF CHRONIC ATRIAL FIBRILLATION

1. It is now recognized that atrial fibrillation (AF) is not a benign condition, as it is associated with a 40% increase in mortality and a doubling of the risk of stroke. 2. The development of AF leads to mechanical, electrophysiological and cellular changes in the atria that tend to sustain AF. This process is known as atrial remodelling. 3. The three electrophysiological elements in the atria that initiate and sustain AF are: (i) shortening of the refractory period and an increase in dispersion; (ii) slowing of conduction velocity; and (iii) the presence of triggerin. foci. 4. As AF is a heterogeneous disorder, therapeutic strategies include the use of devices (pacemakers and atrial defibrillators), radiofrequency ablation (focal ablation or the creation of linear lines) and drug therapy that may reverse a remodelle. atrium.     

Unknown Uterine Sears, Unknown Risks

EDITORIAL COMMENT: We accepted these case reports for publication not only to remind readers that a classical Caesarean scar is more likely than a lower uterine segment scar to rupture or dehisce, but also to stress that women should be counselled appropriately when classical Caesarean section has been performed. Our Australian population is also mobile and women may not return to the same institution or obstetrician for their next confinement. Tracing the details of a previous delivery from another hospital or practitioner even in the same community should be a routine enquiry when a patient has had a Caesarean section in a previous pregnancy but the required information is often difficult to obtain. The woman herse(fis the essential repository for this information. It should also be noted that the recent increase in the number of Caesarean sections performed for fetal indications before 30 weeks' gestation has resulted in more vertical incisions because of a poorly formed lower uterine segment.     

BUERGER'S DISEASE IN HONG KONG: A REVIEW OF 89 CASES

Background : A retrospective analysis of 103 case records from 1978 to 1996 with a provisional diagnosis of Buerger's disease was undertaken at the Department of Surgery, University of Hong Kong, Queen Mary Hospital. The aim of the study was to elucidate the clinical course and evaluate the results of surgical intervention of Buerger's disease in Hong Kong Chinese people. Methods : Fourteen patients were subsequently excluded from the study because of inability to fulfil our diagnostic criteria. Data on clinical presentation, investigations, indications and results of surgical intervention were reviewed. Sympathectomies and arterial reconstructions were performed on 42 and four patients, respectively, for critical ischaemia or rest pain. Outcome was analysed with respect to the rate of ulcer healing, pattern of recurrence and limb loss. Results : The patients were all young male heavy smokers with a mean age of 36.5 years. The majority of patients (80%) presented with ischaemic ulceration or gangrene. Vascular reconstruction was undertaken in four patients and satisfactory long-term results were obtained in three patients. Sympathectomy was able to relieve symptoms in 87% of operated patients and ischaemic ulceration healed in 2.6 (mean) ± 1.7 (SD) months after the operation. If the patient continued to smoke, surgical intervention did not exempt the patient from a relapse or amputation. Conclusion : Sympathectomy provides short-term pain relief and promotes ulcer healing in patients with Buerger's disease but carries no long-term benefit. Complete abstinence from smoking is the only means of arresting the progression of the disease.     

Predicting spontaneous early neurological recovery after acute ischemic stroke

We assessed predictors of spontaneous early neurological recovery after acute ischemic stroke by means of multivariate analysis in a cohort of 1,473 consecutive patients treated at one academic center. At hospital discharge, spontaneous neurological improvement or good outcome was defined as grades 0-2 of the Rankin scale, and poor outcome (no improvement or in-hospital death) as grades 3-5. Spontaneous recovery of neurological deficit at the time of discharge from the hospital was observed in 16% of patients with cerebral infarction (n = 238). Dysarthria-clumsy hand syndrome improved in 44% of patients and was the only variable significantly associated with in-hospital functional recovery in three logistic regression models that in addition to lacunar syndromes, included demographic variables, cardiovascular risk factors, and clinical variables [odds ratio (OR) 2.56], neuroimaging findings (OR 2.48), and outcome data (OR 2.39), respectively. Clinical factors related to severity of infarction available at stroke onset have a predominant influence upon in-hospital outcome and may help clinicians to assess prognosis more accurately. Our work gives a contribution into prognostic factors after acute ischemic stroke. With regard to patterns of stroke, dysarthria-clumsy hand syndrome was a significant predictor of spontaneous in-hospital recovery in ischemic stroke patients.     

Brain abscess mimicking brain tumor

We review our experience with brain abscesses presenting as primary brain tumor over a 5-year period (1983 to 1988). Four of 66 (6%) patients admitted with the diagnosis of primary brain tumor by computed tomographic scans were found at craniotomy to have brain abscesses. Periapical abscesses found after surgery were determined to be the cause of brain abscess in two of four patients. Our experience suggests that periapical abscess may be a more frequent cause of brain abscess than previously thought, and should be considered before surgery in patients with a suspected brain tumor.