Interpretation of time-to-event outcomes in randomized trials: an online randomized experiment.

Background: Multiple features in the presentation of randomized controlled trial (RCT) results are known to influence comprehension and interpretation. We aimed to compare interpretation of cancer RCTs with time-to-event outcomes when the reported treatment effect measure is the hazard ratio (HR), difference in restricted mean survival times (RMSTD), or both (HR+RMSTD). We also assessed the prevalence of misinterpretation of the HR. Methods: We carried out a randomized experiment. We selected 15 cancer RCTs with statistically significant treatment effects for the primary outcome. We masked each abstract and created three versions reporting either the HR, RMSTD, or HR+RMSTD. We randomized corresponding authors of RCTs and medical residents and fellows to one of 15 abstracts and one of 3 versions. We asked how beneficial the experimental treatment was (0-10 Likert scale). All participants answered a multiple-choice question about interpretation of the HR. Participants were unaware of the study purpose. Results: We randomly allocated 160 participants to evaluate an abstract reporting the HR, 154 to the RMSTD, and 155 to both HR+RMSTD. The mean Likert score was statistically significantly lower in the RMSTD group when compared with the HR group (mean difference -0.8, 95% confidence interval, -1.3 to -0.4, P < 0.01) and when compared with the HR+RMSTD group (difference -0.6, -1.1 to -0.1, P = 0.05). In all, 47.2% (42.7%-51.8%) of participants misinterpreted the HR, with 40% equating it with a reduction in absolute risk. Conclusion: Misinterpretation of the HR is common. Participants judged experimental treatments to be less beneficial when presented with RMSTD when compared with HR. We recommend that authors present RMST-based measures alongside the HR in reports of RCT results.

Effectiveness of oral chlorhexidine on nosocomial pneumonia, causative micro-organisms and mortality in critically ill patients: a systematic review and meta-analysis.

We carried out a systematic review and meta-analysis of randomized trials to explore the effectiveness of oral chlorhexidine on nosocomial pneumonia, causative bacteria, and mortality. PubMed, Embase, and the Cochrane Register of Controlled Trials were searched for randomized trials in critically ill patients receiving oral chlorhexidine. Odds ratios (OR) were pooled with the random effects model. Twenty-two randomized trials including 4277 patients were identified. Chlorhexidine significantly reduced the incidence of nosocomial pneumonia (OR 0.66; 95% confidence interval [CI] 0.51-0.85) and ventilator-associated pneumonia (OR 0.68, 95% CI 0.53-0.87). There was a significant reduction of nosocomial pneumonia due to both Gram-positive (OR 0.41; 95% CI 0.19-0.85) and Gram-negative (OR 0.68; 95% CI 0.51-0.90) bacteria, but only pneumonia due to "normal" flora (OR 0.51; 95% CI 0.33-0.80). The subgroup analysis revealed a significant benefit of chlorhexidine on nosocomial pneumonia in surgical patients only (OR 0.52; 95% CI 0.33-0.82). Mortality was not affected. This review indicates that in critically ill, mainly surgical, patients, oral chlorhexidine reduces nosocomial pneumonia, ventilator-associated pneumonia, nosocomial pneumonia due to Gram-positive and Gram-negative bacteria, and due to "normal" flora, without affecting mortality. Further studies should explore the efficacy of oral chlorhexidine in non-surgical critically ill population.

Factors influencing the clinical outcome of methicillin-resistant Staphylococcus aureus bacteraemia.

Methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is associated with high mortality due to a combination of host, pathogen and therapy related factors. This was a retrospective exploratory study to evaluate host, pathogen and therapy related factors influencing the clinical outcome of MRSA bacteraemia in a UK teaching hospital setting. Of the 38 consecutive episodes of MRSA bacteraemia over a 1-year period, 16 of 38 (40%) patients died at 1 month and 21/38 (55%) died at 6 months. Univariate analysis revealed age (p < 0.006), mean serum vancomycin level (p < 0.035), agr group I (p < 0.036) and set4-var2_11 gene (p < 0.036) at 1 month; and age (p < 0.004) and set4-var2_11 gene (p < 0.002) at 6 months as significant factors. However, there was no association between first trough vancomycin concentration and outcome at 1 month. Multivariate survival analysis from time of admission showed, for each one year increase in age, a patient is 1.121 (95% CI 1.006-1.250, p < 0.007) times more likely to die at any particular point in time, and patients with a mean serum vancomycin level of <10 mg/L, the odds ratio of adverse outcome is 16.129 (95% CI 2.398-111.111) compared to patients with a mean serum level >10 mg/L. A variety of host, pathogen, and therapy related factors influence the clinical outcome of MRSA bacteraemia.

Hybrid and complex glycans are linked to the conserved N-glycosylation site of the third eight-cysteine domain of LTBP-1 in insect cells.

Covalent association of LTBP-1 (latent TGF-beta binding protein-1) to latent TGF-beta is mediated by the third eight-cysteine (also referred to as TB) module of LTBP-1, a domain designated as CR3. Spodoptera frugiperda (Sf9) cells have proved a suitable cell system in which to study this association and to produce recombinant CR3, and we show here that another lepidopteran cell line, Trichoplusia niTN-5B1-4 (High-Five) cells, allows the recovery of large amounts of functional recombinant CR3. CR3 contains an N-glycosylation site, which is conserved in all forms of LTBP known to date. When we examined the status of this N-glycosylation using MALDI-TOF mass spectrometry and enzymatic analysis, we found that CR3 is one of the rare recombinant peptides modified with complex glycans in insect cells. Sf9 cells mainly processed the fucosylated paucomannosidic structure (GlcNAc)(2)(Mannose)(3)Fucose, although hybrid and complex N-glycosylations were also detected. In High-Five cells, the peptide was found to be modified with a wide variety of hybrid and complex sugars in addition to paucomanosidic oligosaccharides. Most glycans had one or two fucose residues bound through alpha1,3 and alpha1,6 linkages to the innermost GlcNAc. On the basis of these results and on the structure of an eight-cysteine domain from fibrillin-1, we present a model of glycosylated CR3 and discuss the role of glycosylation in eight-cysteine domain protein-protein interactions.

Venous sequelae. Part 2: Other influencing factors and techniques for dealing with the problem.

In a previous paper, the nature of venous sequelae were described, and the etiologic factors of mechanical and drug injury related to the development of superficial vein thrombosis were addressed. This paper deals with additional factors that may be involved or that have been exposed for reducing or eliminating the problem.

Functional results in oral cavity reconstruction using reinnervated versus nonreinnervated free fasciocutaneous grafts.

Recent advances in free-tissue transfer have given the otolaryngologist--head and neck surgeon a number of reliable options for reconstruction of the oral cavity following ablative procedures. One recent modification has been the transfer of free reinnervated fasciocutaneous grafts in the hope of enhancing oral rehabilitation following surgery. To assess the efficacy of this modification, a protocol was established to retrospectively evaluate patients that received either reinnervated or non-reinnervated free-tissue transfers. Factors including site, surgical resection, type of tissue transfer, and follow-up period were controlled. Evaluation of free-graft sensory return and quality of life was carried out through physical examination and patient interview. Speech assessment was carried out using standardized tests of intelligibility administered by a speech pathologist. Swallowing assessment was carried out with videocinefluoroscopic and scintigraphic techniques, and the oropharyngeal swallow efficiency was calculated. Sensory return in the reinnervate free grafts was superior; however, there was not statistical difference between groups in the speech and swallowing tests. Quality of life was judged to be good in both groups. Sensory return and functional outcome in intraoral reconstruction after tumour ablation was reviewed and discussed

Allegations of children's involvement in ritual sexual abuse: clinical experience of 20 cases.

Twenty cases were evaluated in which allegations had been made of children being involved in ritual sexual abuse (RSA). A selection of case histories are presented together with a summary of the salient points in the other cases. Using a standard format developed for assessing the validity of allegations in sexual abuse cases, it was concluded that false allegations of ritual sexual abuse occurred in three-quarters of the cases and true allegations only in one-quarter. This high rate of false allegations is unlike the author's clinical experience in other cases of child sexual abuse where the rate of false allegations is much lower and similar to other published series. Reasons for the high rate of false allegations are discussed.

Transfemoral liver biopsy by forceps: a review of 104 consecutive procedures.

PURPOSE: Transvenous liver biopsy is performed on patients with contraindications to percutaneous biopsy. Transfemoral liver biopsy has not been widely reported, and we present our experience of 104 consecutive procedures. METHODS: During a 30-month period, 88 patients underwent 104 transfemoral liver biopsies. Under fluoroscopic guidance a 9 Fr curved introducer catheter is passed into the right hepatic vein via a standard femoral sheath. A 7 Fr biopsy forceps is then passed into the liver, opened and wedged. Prior to biopsy, the image intensifer is rotated so the relation of the capsular surface to the biopsy site is verified and capsular perforation avoided. RESULTS: Tissue samples obtained in 97 of 104 procedures (93%) were adequate for diagnosis in 83 (80%). Complications occurred in six procedures (6%) including two capsular perforations; the latter two were treated by coil embolization. CONCLUSION: We found transfemoral liver biopsy using forceps to be a safe, well-tolerated procedure with a high diagnostic yield and it is a technically easy alternative to the transjugular approach using large needles.

Disruption of the structure of larval foraging behaviour in interspecific hybrids in Drosophila.

Larval foraging behaviour in two sibling species, Drosophila pavani and Drosophila gaucha belonging to the mesophragmatica species group, is described. Interspecific hybrid larvae derived from both reciprocal crosses of the parent species show disruption in the organization of their behaviour, leading to lower mean feeding rates. This, together with interactions involving biotic residues, described elsewhere, is likely under competitive conditions to contribute to reduced fitness of the hybrids relative to the parent species.

The late reduction of carpal dislocations.

Five cases are reported in which open reduction of a lunate or peri-lunar dislocation was carried out after a delay of two weeks to six months. Results were poor in terms of range of movement and X-ray appearance, but function was surprisingly good, all patients returning to normal activities including heavy manual work. One patient later underwent excision of the radial styloid with an avascular scaphoid fragment; this apart, there were no requests for further surgical treatment. Open reduction remains a reasonable choice in the treatment of late presentation of lunate and perilunar dislocation.

Wegener's granulomatosis: findings from computed tomography of the chest in 10 patients.

Radiographs and computed tomography (CT) scans of the chest were reviewed for 10 patients with pathologically proven Wegener's granulomatosis. The CT scans revealed multiple pulmonary nodules in seven patients and a single nodule in one. The nodules ranged in diameter from 2 mm to 7 cm, and most had irregular margins. All of the nodules larger than 2 cm in diameter showed evidence of cavitation in the CT scans. Additional CT findings included associated areas of consolidation (in two patients), pleural thickening (in two) and pleural effusion (in two). Chest radiographs were available for eight patients, and the CT scans contributed information additional to that available from the radiographs for seven of these. In one patient lung nodules were visible in the CT scans but could not be distinguished from surrounding areas of consolidation in the chest radiographs. CT revealed additional nodules in five of the six patients in whom multiple nodules were seen in chest radiographs and in one of these also revealed cavitation tht was not visible in plain radiographs. CT excluded the possibility of a nodule that was suspected from the chest radiographs in a patient who had been treated previously for Wegener's granulomatosis. The authors conclude that Wegener's granulomatosis is characterized in CT scans by multiple nodules with irregular margins and by cavitation in nodules larger than 2 cm in diameter. CT may also demonstrate nodules and cavitation not apparent in radiographs.

Hypopituitarism in the elderly in the presence of elevated thyroid stimulating hormone levels.

Two cases of primary hypothyroidism with hypopituitarism in elderly patients are reported. The elevated levels of thyroid stimulating hormone led to delay in the recognition of accompanying pituitary failure. Elderly patients should not be commenced on thyroxine replacement therapy until the possibility of hypopituitarism and cortisol deficiency has been excluded.

CT diagnosis of bronchial rupture.

Computed tomography in a patient with unsuspected rupture of the left mainstem bronchus revealed shift of the trachea to the right, with the remainder of the mediastinum being shifted to the left. The left mainstem bronchus was visualized only in its most proximal course. The combination of deviation of the trachea from the remainder of the mediastinum and abrupt cut off of the left mainstem bronchus suggested the diagnosis of ruptured bronchus.

Behaviour modification in the treatment of sleep problems occurring in young children: a controlled trial using health visitors as therapists.

A controlled trial of behaviour modification in the treatment of sleep problems is described. The subjects were 51 children aged 4 months to 4 1/2 years (mean 20 months) recruited from the community by health visitors (specialist nurses based in the community). In the experimental procedure health visitors were trained and supported in the use of behaviour modification. At 6 months follow-up both control and experimental groups showed equally marked improvement. Reasons for the failure to demonstrate an effect are discussed.

Haemodynamic and metabolic effects of prophylactic nitroglycerin infusion in the immediate period following coronary artery bypass grafting.

This is a preliminary report of work in progress to assess the effects of prophylactic nitroglycerin infusion in patients undergoing coronary artery vein grafting. So far 14 patients have been studied. They were divided into two groups to receive either nitroglycerin (1 microgram kg-1 min-1) or placebo (5% dextrose). The infusion was commenced on removal of the aortic cross-clamp after completion of the distal anastomoses of the grafts. During cardiopulmonary bypass myocardial protection was provided by cold potassium cardioplegia and systemic hyopthermia. For 2 hours after cessation of cardiopulmonary bypass simultaneous samples of coronary sinus and femoral arterial blood were taken to estimate lactate concentrations and oxygen saturation. No differences were found between the groups. At the same times haemodynamic measurements were made. There was a statistically significant increase in cardiac index in the nitroglycerin group up to 30 minutes post cardiopulmonary bypass. There was also a statistically significant fall in systemic and pulmonary vascular resistances with no differences in systemic or pulmonary arterial pressures. There was no difference in central venous or pulmonary capillary wedge pressures. Patients receiving nitroglycerin seemed more stable cardiovascularly than those receiving placebo. In conclusion nitroglycerin improves cardiac output in the immediate post bypass period following cold potassium cardioplegia.

A case of left atrial haemangioma: echocardiographic, surgical, and morphological features.

A slow growing encapsulated haemangioma of the left atrium was diagnosed by means of cross sectional echocardiography. The heterogeneous nature of the tumour was reflected in a central area of relative echolucency. After successful surgical removal of the tumour, the patient's symptoms of lethargy and limited exercise capacity improved considerably.