Treatment preference and recruitment to pediatric RCTs: A systematic review.

BACKGROUND: Recruitment to pediatric randomised controlled trials (RCTs) can be a challenge, with ethical issues surrounding assent and consent. Pediatric RCTs frequently recruit from a smaller pool of patients making adequate recruitment difficult. One factor which influences recruitment and retention in pediatric trials is patient and parent preferences for treatment. PURPOSE: To systematically review pediatric RCTs reporting treatment preference. METHODS: Database searches included: MEDLINE, CINAHL, EMBASE, and COCHRANE.Qualitative or quantitative papers were eligible if they reported: pediatric population, (0-17 years) recruited to an RCT and reported treatment preference for all or some of the participants/parents in any clinical area. Data extraction included: Number of eligible participants consenting to randomisation arms, number of eligible patients not randomised because of treatment preference, and any further information reported on preferences (e.g., if parent preference was different from child). RESULTS: Fifty-two studies were included. The number of eligible families declining participation in an RCT because of preference for treatment varied widely (between 2 and 70%) in feasibility, conventional and preference trial designs. Some families consented to trial involvement despite having preferences for a specific treatment. Data relating to 'participant flow and recruitment' was not always reported consistently, therefore numbers who were lost to follow-up or withdrew due to preference could not be extracted. CONCLUSIONS: Families often have treatment preferences which may affect trial recruitment. Whilst children appear to hold treatment preferences, this is rarely reported. Further investigation is needed to understand the reasons for preference and the impact preference has on RCT recruitment, retention and outcome.

Improving the Prediction of Mortality in the High Model for End-Stage Liver Disease Score Liver Transplant Recipient: A Role for the Left Atrial Volume Index.

Left atrial volume index (LAVI) is an echocardiographic measurement used in assessing diastolic dysfunction, and is associated with mortality in many populations. In this retrospective cohort study including 254 patients, we investigated whether LAVI is an independent predictor of post-liver transplantation mortality using multivariable Cox regression. We found that elevated LAVI was associated with increased mortality among patients with high Model for End-Stage Liver Disease (MELD) scores, but not among those with lower MELD scores, indicating that recipients with high LAVI values and high MELD scores may represent patients at an increased risk of post-transplantation mortality. Specifically, there was a statistically significant interaction between LAVI and MELD score (P = .006) such that for patients with MELD scores ≥33, LAVI >27 mL/m2 was associated with increased mortality (hazard ratio = 2.3; 95% confidence interval, 1.04-5.20; P = .04.) We further show that the inclusion of LAVI in a multivariable model led to a statistically significant improvement in the ability to predict post-liver transplantation mortality, with an increase in the model's C-statistic from 0.68 to 0.71. The incorporation of LAVI in multivariable risk models may be useful in the selection of transplant recipients with high MELD scores, and may be helpful in decreasing the probability of futile transplantation.

Cascades on a stochastic pulse-coupled network.

While much recent research has focused on understanding isolated cascades of networks, less attention has been given to dynamical processes on networks exhibiting repeated cascades of opposing influence. An example of this is the dynamic behaviour of financial markets where cascades of buying and selling can occur, even over short timescales. To model these phenomena, a stochastic pulse-coupled oscillator network with upper and lower thresholds is described and analysed. Numerical confirmation of asynchronous and synchronous regimes of the system is presented, along with analytical identification of the fixed point state vector of the asynchronous mean field system. A lower bound for the finite system mean field critical value of network coupling probability is found that separates the asynchronous and synchronous regimes. For the low-dimensional mean field system, a closed-form equation is found for cascade size, in terms of the network coupling probability. Finally, a description of how this model can be applied to interacting agents in a financial market is provided.

Anesthetic management for resection of hepatic paraganglioma metastatic from the donor organ in an orthotopic liver transplant recipient: a case report.

This is a case report of the anesthetic management for the hepatic resection of a metastatic paraganglioma in a patient with a history of prior orthotopic liver transplantation. Of interest, the metastatic paraganglioma originated from the donor organ. The patient is an 80-year-old woman with multiple medical problems including a history of cryptogenic cirrhosis who underwent successful orthotopic liver transplantation 9 years prior. She later presented with signs and symptoms of catecholamine excess suggestive of a catecholamine-producing tumor (paraganglioma or pheochromocytoma). Elevated urine catecholamine levels and radiographic evidence of a paraganglioma in the transplanted liver metastatic from the donor organ confirmed the diagnosis. Radiofrequency ablation of the tumor and surgical resection was previously attempted without success. We describe the anesthetic management for the successful resection of the metastatic hepatic paraganglioma, which was complicated by profound intraoperative hypertension and hypotension that necessitated the use of multiple vasoactive infusions, extensive surgical blood loss requiring blood transfusion, and difficult glycemic control in an insulin-dependent diabetic patient. The postoperative course is also described. This unique case presented the anesthesia team with challenges specific to both surgery for hepatic resection as well as for catecholamine-secreting tumors. We are not aware of any reports of paragangliomas of either donor or recipient origin involving a transplanted liver, making this the first such report to the best of our knowledge.

Liver transplantation outcome in patients with angiographically proven coronary artery disease: a multi-institutional study.

Over the last decade the age of liver transplant (LT) recipients and the likelihood of coronary artery disease (CAD) in this population have increased. There are no multicenter studies that have examined the impact of CAD on LT outcomes. In this historical cohort study, we identified adult LT recipients who underwent angiography prior to transplantation at seven institutions over a 12-year period. For each patient we recorded demographic data, recipient and donor risk factors, duration of follow-up, the presence of angiographically proven obstructive CAD (≥50% stenosis) and post-LT survival. Obstructive CAD was present in 151 of 630 patients, the CAD(+) group. Nonobstructive CAD was found in 479 patients, the CAD(-) group. Patient survival was similar for the CAD(+) group (adjusted HR 1.13, CI = [0.79, 1.62], p = 0.493) compared to the CAD(-) group. The CAD(+) patients were further stratified into severe (CADsev, >70% stenosis, n = 96), and moderate CAD (CADmod, 50-70% stenosis, n = 55) groups. Survival for the CADsev (adjusted HR = 1.26, CI = [0.83, 1.91], p = 0.277) and CADmod (adjusted HR = 0.93, CI = [0.52, 1.66], p = 0.797) groups were similar to the CAD(-) group. We conclude that when current CAD treatment strategies are employed prior to transplant, post-LT survival is not significantly different between patients with and without obstructive CAD.

Protection from experimental ventilator-induced acute lung injury by IL-1 receptor blockade.

BACKGROUND: Clinical studies have shown that injurious mechanical ventilation is associated with increased airspace and plasma levels of interleukin-1beta (IL-1beta); however, the potential therapeutic value of IL-1 inhibition in acute lung injury has not been thoroughly investigated. A study was undertaken to determine if IL-1 signalling is a necessary early event in the pathogenesis of experimental ventilator-induced lung injury. METHODS: Mice deficient in IL-1 receptor type 1 (IL1R1) and rats treated with IL-1 receptor antagonist (IL-1Ra) were mechanically ventilated with high tidal volume (30 ml/kg) and the effect of IL-1 signalling blockade on the severity of lung injury was determined. RESULTS: Permeability, as measured by radiolabelled albumin flux, was significantly lower in IL1R1 null mice than in wild-type mice during injurious ventilation (p<0.05). IL-1Ra significantly decreased protein permeability and pulmonary oedema in rats during injurious ventilation and also decreased airspace and plasma levels of the chemokine CXCL1 and airspace neutrophils. IL-1Ra decreased expression of NOS2 and ICAM-1 mRNA in whole lung. Bronchoalveolar lavage fluid levels of RTI40, a marker of type I cell injury, were 2.5 times lower following IL-1Ra treatment (p<0.05). In isolated type II pneumocytes, IL-1beta reduced electrical resistance and increased transepithelial permeability. CONCLUSIONS: IL-1 contributes to alveolar barrier dysfunction in VILI by promoting lung neutrophil recruitment and by increasing epithelial injury and permeability. Because preserved alveolar barrier function is associated with better outcomes in patients with acute lung injury, these data support further testing of IL-1Ra for the treatment of acute lung injury.

Evaluation of patients for pulmonary endarterectomy.

Chronic thromboembolic obstruction of the pulmonary vascular bed has been increasingly recognized as a treatable form of pulmonary hypertension, with surgery referred to as a pulmonary endarterectomy. Careful evaluation of patients with pulmonary hypertension and proper selection of those with surgically accessible, chronic thromboembolic disease are critical determinants for a successful outcome from this operation. This article describes the clinical presentation, appropriate evaluation, and an approach to surgical selection for patients with chronic thromboembolic pulmonary hypertension.

The significance and clinical factors associated with a subcentimeter resection of colorectal liver metastases.

BACKGROUND: Prognosis after resection of colorectal liver metastases is influenced by various factors. A positive margin of resection (MOR) has been shown to adversely influence prognosis. Although a 1-cm MOR has been accepted as adequate, the data to support this guideline are sparse. METHODS: Our hepatobiliary database was queried for patients who underwent liver resection for colorectal metastases between January 1992 and July 2003. All patients were divided into three groups: MOR <.5 cm (group A), .5 to 1 cm (group B), and >1 cm (group C). Operative reports from each hepatic resection were analyzed to determine local factors that may have contributed to a subcentimeter MOR. RESULTS: A total of 112 patients (67 men and 45 women) underwent liver resection for colorectal metastases with negative margins. Fifty-three patients were in group A, 26 patients were in group B, and 33 patients were in group C. Group C demonstrated decreased local recurrence (LR; P = .003), distant recurrence (DR; P = .008), and disease-free recurrence (P = .002). A significant difference in the overall time to LR (P = .003), time to DR (P = .003), and disease-free survival (P = .002) was also demonstrated. Factors associated with a subcentimeter MOR included nonanatomical resection (P = .043), proximity to a major vessel (P = .003), and central location (P = .002). CONCLUSIONS: A <1-cm resection for colorectal liver metastases is associated with increased LR and DR, as well as decreased disease-free survival. When a nonanatomical resection is performed, a MOR >1 cm should be attempted, because an adequate margin is often underestimated. Considerations should be made for extended resections when tumors are centrally located or near major vessels.

The influence of age on outcome after operation for the carpal tunnel syndrome. A prospective study.

Decompression of the carpal tunnel is a common surgical procedure. Although the incidence of the carpal tunnel syndrome increases with age, there is no clear information available on the outcome of surgery in relation to age. We studied prospectively 87 consecutive patients who underwent decompression, using a validated self-administered questionnaire, and found that improvement in symptoms and function decreased with increasing age. This was most marked in patients over the age of sixty years.

Antimicrobial resistance in Salmonella isolated from animals and their environment in England and Wales from 1988 to 1999.

Resistance to 16 antimicrobial agents was monitored in 109,125 Salmonella cultures isolated from animals, their environment and feedstuffs between 1988 and 1999. The sensitivity of the 6512 isolates of Salmonella enterica enterica serotype Dublin to all the antimicrobial agents tested varied from 98.2 per cent in 1997 to 99.7 per cent in 1990 and 1996. In contrast, among 28,053 isolates of Salmonella enterica enterica serotype Typhimurium, there was a marked decrease in their sensitivity to all the antimicrobial agents tested, from 57.4 per cent in 1992 to 7.6 per cent in 1995, owing to the widespread occurrence in farm animals of S Typhimurium isolates of the definitive type DT104, resistant to ampicillin, sulphonamides, streptomycin, chloramphenicol and tetracyclines, although the percentage of sensitive isolates increased to 18.4 per cent in 1999, when the incidence of DT104 had decreased. Some isolates of DT104 also showed an increase in resistance to potentiated sulphonamides (2.4 per cent in 1989 to 19.2 per cent in 1999) and nalidixic acid (0 per cent in 1992, 3.8 per cent in 1995 to a peak of 16.9 per cent in 1998). In 1996, 5.1 per cent of 1086 isolates of S Typhimurium from cattle and 35.9 per cent of 192 isolates of S Typhimurium from poultry showed resistance to nalidixic acid. Of the other 74,528 Salmonella isolates, the percentage of strains sensitive to all the antimicrobials tested decreased slightly from 88.2 per cent in 1988 to 70.6 per cent in 1996 and then increased slightly to 73.7 per cent in 1999. The commonest of these other Salmonella serotypes was Salmonella Enteritidis (20,982), which remained predominantly susceptible (ranging from 81.4 to 97.4 per cent) during the study period. Few isolates were resistant to commonly used veterinary antimicrobials, for example, furazolidone, the use of which was banned in 1990, and the aminoglycoside, apramycin.

The transcription factors NF-kappab and AP-1 are differentially regulated in skeletal muscle during sepsis.

Sepsis is associated with increased muscle proteolysis and upregulated transcription of several genes in the ubiquitin-proteasome proteolytic pathway. Glucocorticoids are the most important mediator of sepsis-induced muscle cachexia. Here, we examined the influence of sepsis in rats on the transcription factors NF-kappaB and AP-1 in skeletal muscle and the potential role of glucocorticoids in the regulation of these transcription factors. Sepsis was induced by cecal ligation and puncture (CLP). Control rats were sham-operated. NF-kappaB and AP-1 DNA binding activity was determined by electrophoretic mobility shift assay (EMSA) in extensor digitorum longus muscles at different time points up to 16 h after sham-operation or CLP. Sepsis resulted in an early (4 h) upregulation of NF-kappaB activity followed by inhibited NF-kappaB activity at 16 h. AP-1 binding activity was increased at all time points studied during the septic course. When rats were treated with the glucocorticoid receptor antagonist RU38486, NF-kappaB activity increased, whereas AP-1 activity was not influenced by RU38486. The results suggest that NF-kappaB and AP-1 are differentially regulated in skeletal muscle during sepsis and that glucocorticoids may regulate some but not all transcription factors in septic muscle.

Natural and experimental infection of normal cattle with Escherichia coli O157.

The objective of the study was to determine the effects of inoculating cattle orally with a strain of Escherichia coli O157:H7 (A84/92). However, before they were challenged two of the six calves were found to be infected naturally with a wild-type strain of E coli O157 and two more of them became infected later. The number of daily faeces samples from which the wild-type E coli O157 was isolated ranged from one to 10. After they were inoculated, A84/92 was detected in all the calves' faeces on one to six of the next 14 days, and later from the faeces samples of three calves on two, three, and 11 occasions, the last occasion being between 19 and 51 days after inoculation. Two calves were redosed with A84/92, and the organism was isolated on a further five and 15 occasions, the last being after 20 and 58 days. In three dry cows, A84/92 was isolated from the faeces on three to 11 of the 14 days after they were inoculated. Two of the cows were redosed and from one of them it was isolated on 15 occasions, the last being 44 days after the initial infection; in the other cow no further isolation was made. In three lactating cows, it was detected on three to four of the 14 days after they were inoculated, and similar results were obtained after they were reinoculated. None of the animals showed clinical signs and no lesions were detected in the intestines of the calves. Three calves had a serological response to E coli O157 but, with the exception of one cow which had a slight increase to IgM levels, no serological changes were observed in the adult cattle.

Antibiotic resistance monitoring in bacteria of animal origin: analysis of national monitoring programmes.

Methods of antibiotic resistance monitoring of bacteria from animals in 12 European countries were surveyed in 1998. Most laboratories used disk diffusion methods, usually expressing results qualitatively, although a few also expressed the results either as MICs or zone diameters. The number of antibiotics used ranged from 5 to 37 (mean 15) and the most common antibacterials were streptomycin, gentamicin, neomycin, ampicillin, tetracyclines, chloramphenicol and sulphonamides. Salmonellae were monitored by most centres but few-tested campylobacter regularly. Escherichia coli from a wide range of animal species were tested in nine countries. Enterococci were tested on a limited ad hoc basis in six countries. Staphylococci, streptococci and pasteurellae were also frequently monitored but the number of isolates tested showed wide variation. Overall the presentation of the results differed, but most programmes used disk diffusion, control strains and monitored similar bacteria. Thus, it may be possible to harmonise monitoring programmes within the EU.

Enterobacter agglomerans spondylodiscitis: a possible, unrecognized complication of tetracycline therapy.

STUDY DESIGN: This case report describes infection in a lumbar disc in a healthy young man with an organism of low pathogenicity. The patient was taking a prolonged course of antibiotics at the time the infection occurred. OBJECTIVE: To describe this unique case of infective spondylodiscitis. SUMMARY OF BACKGROUND DATA: To the authors' knowledge, spinal infection with Enterobacter agglomeranshas never been reported. This organism is a transient gut colonizer, and may have established itself secondary to the patient's prolonged ingestion of tetracycline for acne. METHODS: This 22-year-old farmer had spontaneous lumbar back pain. Radiologic investigations showed an abnormality in the L4-L5 disc region, and together with other investigations, were suggestive of infection. The diagnosis was confirmed by surgical aspiration. RESULTS: Antibiotic therapy was administered, and the patient made a complete recovery. Follow-up radiographs showed a complete loss of the L4-L5 disc space with only minimal bone destruction. CONCLUSION: A unique cause of infective lumbar discitis is presented. Several features of this case are unusual. The magnetic resonance findings were not readily diagnostic. The cultured organism is usually nonpathogenic. The infection may have been secondary to prolonged tetracycline therapy.

Molluscan engrailed expression, serial organization, and shell evolution.

Whether the serial features found in some molluscs are ancestral or derived is considered controversial. Here, in situ hybridization and antibody studies show iterated engrailed-gene expression in transverse rows of ectodermal cells bounding plate field development and spicule formation in the chiton, Lepidochitona cavema, as well as in cells surrounding the valves and in the early development of the shell hinge in the clam, Transennella tantilla. Ectodermal expression of engrailed is associated with skeletogenesis across a range of bilaterian phyla, suggesting a single evolutionary origin of invertebrate skeletons. The shared ancestry of bilaterian-invertebrate skeletons may help explain the sudden appearance of shelly fossils in the Cambrian. Our interpretation departs from the consideration of canonical metameres or segments as units of evolutionary analysis. In this interpretation, the shared ancestry of engrailed-gene function in the terminal/posterior addition of serially repeated elements during development explains the iterative expression of engrailed genes in a range of metazoan body plans.

Epidemiology and characterization of animal Salmonella enterica subspecies Enterica serotype typhimurium DT104 in Hungary.

Reports on the internationally emerging significance of multiresistant zoonotic Salmonella in animals and man prompted studies to estimate the significance of multiresistant Salmonella enterica subspecies enterica serotype Typhimurium (S. Typhimurium) phage type DT104 of animal origin in Hungary. A collection of 231 strains (primarily of goose, turkey, poultry and porcine origin from the years 1997-1998) was tested for resistance against 7 selected antibiotics (ampicillin, chloramphenicol, enrofloxacin, nalidixic acid, streptomycin, tetracycline and sulphamethoxazole). Strains with resistance against 3 or more were defined as multiresistant. All strains were phage typed using Felix-Callow's S. Typhimurium phage typing system, and 91 of them (suspect DT104) were also typed according to Anderson's definitive typing (DT) system. In this study, 14% of animal strains from 1997-1998 was classified as DT104, for which turkey, pig and duck seemed to be the main carriers, and the multiresistant non-DT104 strains represented a further 6% of this collection. The prevalence of DT104 was highest among strains of turkey origin (50%), followed by strains of pig (29%), chicken (25%), duck (19%), and goose (3%) origin. The other DT104 related phage types (DT12 and U302) were only detected in the case of 4 strains (2 of porcine, and one each of turkey and of goose origin). The DT104 corresponded to the Felix-Callow types 2/3 or 2c/3 in each case, except in the case of 3 turkey strains where they corresponded to type 35/3. Nalidixic acid resistance was detected in all multiresistant turkey strains and in some of other animal origin but none of these strains were resistant to enrofloxacin. A retrospective analysis (based on the above relationship) indicated that S. Typhimurium strains corresponding to DT104 could be present and increase in the Hungarian farm animal population from about 2% to 20% between 1985 and 1990, in a manner similar to the emergence of human DT104, as reported elsewhere (Pászti et al., 2000). The 91 suspect DT104 strains were also tested for plasmid profile and for spvC gene indicating the presence of the large serotype specific plasmid (Ssp). No characteristic plasmid profile could be attributed to S. Typhimurium DT104. The serovar-specific large plasmid was detected by PCR for spvC in 100% of DT104 strains and in 77% of the non-DT104 strains. The virulence of two DT104 strains was tested in orally infected day-old chicks and compared with virulence of 4 non-DT104 strains. Higher colonizing virulence of DT104 strains could be established as compared to the other strains.

Transmission of Vero cytotoxin producing Escherichia coli O157 infection from farm animals to humans in Cornwall and west Devon.

A study of Vero cytotoxin producing Escherichia coli (VTEC) O157 infections in Cornwall and West Devon was conducted to identify associations between human infection and contact with farm animals. In three years from November 1994 to October 1997, 63,000 stool specimens were submitted to four participating microbiology laboratories and screened for E. coli O157. Sixty-nine confirmed cases were interviewed to assess the extent of any direct or indirect contact with farm animals. Nine out of 22 investigations conducted on farms--in which animal rectal swabs, faecal specimens, fore-stream milk samples (first draw-off from teats), and various environmental samples were tested--yielded VTEC O157. In seven incidents one or more isolates from animals were indistinguishable from the isolate(s) from the human case(s) using phenotypic and genotypic subtyping. Cases associated with animal contact included farm visitors, holidaymakers, and members of farming families and farm workers.