Early prophylactic inhaled beclomethasone in infants less than 1250 g for the prevention of chronic lung disease

OBJECTIVE:

Inflammation plays an important role in the development of chronic lung disease (CLD), which has become a major cause of morbidity in surviving infants less than 1250 g at birth. The authors hypothesized that the progression of this inflammation and, therefore, the establishment of CLD would be decreased with the use of early prophylactic inhaled corticosteroids. Short, and long term respiratory and neurodevelopmental outcomes were also examined.

DESIGN:

A double-blind, randomized placebo controlled trial.

SETTING:

Level-III neonatal intensive care unit.

POPULATION STUDIED:

Sixty infants less than 1250 g at birth, diagnosed with respiratory distress syndrome and requiring ventilatory support at 72 h of age were enrolled in the study.

INTERVENTION:

Infants enrolled received either placebo or beclomethasone diproprionate by a metered dose inhaler, which was used in-line with the ventilator circuit while the infant was ventilated and then via a spacer until 28 days of age.

RESULTS:

Thirty infants were given beclomethasone and 30 were given placebo. There were two deaths in each group. Among the surviving infants, the frequency of moderate-to-severe CLD was 17% in each study group. Mean time to extubation was not different for beclomethasone compared with placebo at 16.4 and 12.5 days (P=0.12), respectively. The requirement for intravenous corticosteroids was lower in the beclomethasone-treated group (RR 0.67, 95% CI 0.43 to 1.04), although this difference was not statistically significant. The incidence of growth failure, infection and intraventricular hemmorhage did not differ between the two groups. Long term outcomes were not different with respect to the incidence of respiratory re-admissions, cerebral palsy, developmental delay, blindness or deafness.

CONCLUSIONS:

Early treatment with inhaled beclomethasone diproprionate did not reduce the incidence of CLD or decrease the duration of mechanical ventilation. The decrease in intravenous corticosteroid use was not statistically significant. Long term outcome was not affected.     

The handling of uncertainty in economic evaluations of health care strategies

BACKGROUND: The recent development of prospective economic evaluations in association with randomized controlled clinical trials has provided clinical and economic data allowing a statistical analysis of uncertainty. Pertinent comparison of alternative medical strategies in the cost-effectiveness analysis requires analysis of the incremental cost-effectiveness ratio. In this work, we were interested in developing confidence regions of the cost-effectiveness ratio in order to take into consideration its uncertainty which creates a certain number of problems when the denominator approaches zero. Our objectives were to conduct a critical analysis of the different estimations used and examine their application in the decision making process. METHODS: There are two kinds of methods: those based on the density of the estimated ratio (Taylor method, parametric and non-parametric bootstrap methods such as percentile, percentile-t and bias-corrected and accelerated methods) and those based on the bivariate density of the variable pair: difference of average costs, difference of average effects (box method, ellipse method, and Fieller method). RESULTS: We showed that methods based on the density of the ratio become unstable and inapplicable when the statistical difference of average effects tends towards zero. In practice however, data often take on such a pattern. We give an example of an economic evaluation as an illustration. Bivariate density methods do not have this drawback. Moreover, the "mirror decision" phenomenon requires that the region of confidence be a directed single confidence sector for valid decision making. CONCLUSIONS: Uncertainty must be taken into account for all economic evaluations but the use of undirected confidence regions is inappropriate as a decision-making tool.     

Real-time contrast-enhanced ultrasound of the spleen: examination technique and preliminary clinical experience

PURPOSE: To report our preliminary experience in the evaluation of the spleen using a real-time contrast-specific ultrasound module in combination with a second-generation contrast agent. MATERIALS AND METHODS: In a 7-month period, 55 patients (34 males and 21 females, aged 5-77 years) with spleen disorders were evaluated by means of contrast-enhanced ultrasound. Two patients were studied because of baseline evidence of an accessory spleen and both underwent ultrasound follow-up. Twenty-five patients were studied for abdominal trauma and results were correlated with those of helical CT. Three patients were examined for suspected splenic infarction and for all CT correlation was obtained. Finally, twenty-five subjects were examined for focal diseases, such as lymphomas (17 cases) and focal lesions (8 cases); contrast-enhanced US results were correlated with those of CT (8 cases), MRI (2 cases), ultrasound follow-up (8 cases), biopsy (2 cases) or splenectomy (1 case). After an initial baseline study, the contrast-enhanced examinations were carried out using a dedicated unit equipped with a continuous contrast-specific module at low acoustic pressure. The examination started immediately after rapid contrast injection and lasted approximately 4 minutes. In the comparison between baseline and contrast-enhanced ultrasound, the following aspects were considered: detection rate of parenchymal changes, lesion extent (equal to CT, under- or overestimated), and lesion conspicuity (lesion-to-parenchyma gradient, from 0 = absent to 3 = high). RESULTS: In the 2 patients with accessory spleen, an enhancement very similar to that of the adjacent parenchyma was present and a small vascular pedicle was noted. Among the trauma patients, 18 had a direct splenic injury and one showed splenic contraction and hypoperfusion due to shock. In 74% of cases, a peritoneal effusion was demonstrated both with baseline and contrast-enhanced ultrasound; perisplenic blood collections (58% of cases) were identified in 42% of patients by both baseline and contrast-enhanced ultrasound; post-traumatic infarction was always revealed by contrast-enhanced ultrasound (11% of cases) but never by baseline ultrasound; parenchymal injuries were detected with a sensitivity of 63% by baseline ultrasound and a sensitivity of 89% by contrast-enhanced ultrasound. Moreover, contrast-enhanced ultrasound revealed findings undetectable on conventional ultrasound: global splenic hypoperfusion in 2 cases (due to shock in one and pedicle avulsion in the other), intraparenchymal contrast collections in 21% of positive cases (as confirmed by CT), extrasplenic contrast leakage in 1 of 2 cases demonstrated by CT. Of the 3 cases of splenic infarction, baseline sonography only only identified two, whereas the contrast-enhanced examination clearly identified three. Contrast-enhanced ultrasound revealed 35 of 39 focal lesions in patients studied for Hodgkin's disease and splenic focal lesions. Baseline ultrasound had a lower sensitivity (23 lesions). Lesion extension shown by contrast-enhanced sonography was equivalent to that provided by standard methods in 88% of cases (underestimated in 9% and overestimated in 3%); baseline US correctly estimated lesion size in 52% of cases, under- and overestimating them in 35% and 13% of cases, respectively. Lesion conspicuity was graded as 1 (low) in 16%, 2 (moderate) in 67%, and 3 (high) in 17% of the cases identified by enhanced sonography. Baseline ultrasound was less effective: conspicuity was graded as 1 in 42%, 2 in 39%, and 3 in 19% of cases. CONCLUSIONS: The spleen is the ideal organ to be studied with second-generation contrast media due to its superficial location, high vascularity, small size and homogeneous texture. Contrast-enhanced ultrasound is a simple, poorly-invasive and accurate tool for the evaluation of splenic disorders. If our data are confirmed, it will be possible to reduce the use of more complex technologies such as CT and MRI.     

Ventral hernia repair: a study of current practice

Ventral wall hernias are common; despite this, there are no guidelines on the best surgical management. The aim of this study was to examine the types of repair in use for abdominal wall hernias in the West of Scotland over a 3-month period. Data were gathered on 120 patients. There were 60 incisional, 32 umbilical, and 28 epigastric hernias. The main indication for repair was pain (78%), while 12 patients (10%), presented acutely with incarceration or strangulation. The most common method of repair was sutured (55%), followed by mesh (29%) and Mayo repair (16%). There was no correlation between use of mesh and hernia size or whether repair was for a recurrent hernia. Surgical practice varies widely in the repair of ventral wall hernias. Clinical trials are required to establish the best method of repair for this common condition. Electronic Publication     

Low grade fibromyxoid sarcoma of the falciform ligament: a case report

Background  

Low grade fibromyxoid sarcomas (LGFMS) are very rarely seen. They commonly arise from deep soft tissues of the lower extremities. Very few cases of intra-abdominal location have been reported.     

Intraindividual variation in recent stress exposure as a moderator of cortisol and testosterone levels

Intraindividual variation in recent stress exposure and its impact upon cortisol and testosterone was investigated. Over 1 year, 72 young male firefighters completed the Daily Stress Inventories, for 2 shift cycles (16 days), every 3 months. At the end of each 16-day period each participant attended a 1-hr morning assessment session. Saliva samples and blood pressure measurements were taken at 10-min intervals, and at 30 min, a blood sample was drawn. Across the year of assessment, there were significant linear relationships in reported stress and in neuroendocrine activity. In contrast to expectations, as daily stress decreased across the year (p < .008), salivary cortisol increased (p < .001) and testosterone levels decreased (p < .001). Within-subjects comparisons of the sessions with the highest and lowest stress confirmed these linear relationships: Lower stress prior to the assessment session was associated with higher cortisol levels (p < .01). These results, though in contrast to the orthodoxy concerning the association between stress and cortisol, are supported by findings in a number of other studies and may constitute down regulation of cortisol activity following an increment in stress exposure. This research was supported by the Medical Research Council, United Kingdom. We are grateful to the London Fire & Civil Defence Authority for their cooperation.     

Detection of carbamyl phosphate synthetase 1 deficiency using duodenal biopsy samples

The activity of urea cycle enzymes was assayed in duodenal biopsy specimens obtained from a female infant who presented with neonatal hyperammonaemia. All enzyme levels were normal except N-acetyl glutamate-dependent carbamyl phosphate synthetase 1 (CPS1) which was half the mean activity in normal control specimens. A similar deficiency of CPS1 was also shown in duodenal specimens from the patient's mother who became slightly symptomatic after relatively high protein meals and during pregnancy, and had spontaneously modified her diet to one with protein restriction. The patient is growing normally on a dietary regimen similar to that spontaneously adopted by her mother. Urea cycle enzyme activity in the duodenal biopsy material from the controls was similar to that found in the normal human liver and appears to have distinct advantages as a means of assaying for urea cycle defects in patients with hyperammonaemia and their relatives.