Summary Recent spread of avian influenza A (H5N1) virus to poultry and wild birds has increased the threat of human infections with H5N1 virus worldwide. Despite international agreement to stockpile ...antivirals, evidence-based guidelines for their use do not exist. WHO assembled an international multidisciplinary panel to develop rapid advice for the pharmacological management of human H5N1 virus infection in the current pandemic alert period. A transparent methodological guideline process on the basis of the Grading Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to develop evidence-based guidelines. Our development of specific recommendations for treatment and chemoprophylaxis of sporadic H5N1 infection resulted from the benefits, harms, burden, and cost of interventions in several patient and exposure groups. Overall, the quality of the underlying evidence for all recommendations was rated as very low because it was based on small case series of H5N1 patients, on extrapolation from preclinical studies, and high quality studies of seasonal influenza. A strong recommendation to treat H5N1 patients with oseltamivir was made in part because of the severity of the disease. Similarly, strong recommendations were made to use neuraminidase inhibitors as chemoprophylaxis in high-risk exposure populations. Emergence of other novel influenza A viral subtypes with pandemic potential, or changes in the pathogenicity of H5N1 virus strains, will require an update of these guidelines and WHO will be monitoring this closely.
Background Between June 1, 2004, and March 14, 2005, 16 patients in the surgical/medical intensive care unit (ICU) were infected and another 2 were colonized with multidrug-resistant (MDR) ...Acinetobacter baumannii . We describe the systematic investigation initiated to discover an environmental reservoir and a novel measure taken to terminate the outbreak. Methods Cultures were taken from moist areas in the ICU, including sink traps, sink and counter surfaces, drains, and faucets. Strains were characterized using restriction endonuclease analysis. A weekly full drainpipe chase cleansing protocol with sodium hypochlorite (bleach) solution for all 24 ICU and waiting room area sinks connected by common plumbing was initiated in March 2005. Results Eleven of 16 infected patients (69%) had a clonal MDR strain, 1 patient (6%) was infected with an unrelated strain, and in 4 patients (25%) strains were not available for typing. The reservoir for the A baumannii clone was detected in a sink trap within one of the ICU patient rooms that likely represented contamination of the entire horizontal drainage system. The bleaching protocol initiated in March 2005 successfully decontaminated the reservoir and eliminated the MDR A baumannii infections. Conclusion A systematic search for an environmental reservoir followed by decontamination significantly reduced ( P < .01) the incidence of MDR A baumannii infection.
To develop and validate a perfused organ model for characterizing ablations for irreversible electroporation (IRE)-based therapies.
Eight excised porcine livers were mechanically perfused with a ...modified phosphate-buffered saline solution to maintain viability during IRE ablation. IRE pulses were delivered using 2 monopolar electrodes over a range of parameters, including voltage (1,875-3,000 V), pulse length (70-100 µsec), number of pulses (50-600), electrode exposure (1.0-2.0 cm), and electrode spacing (1.5-2.0 cm). Organs were dissected, and treatment zones were stained with triphenyl tetrazolium chloride to demonstrate viability and highlight the area of ablation. Results were compared with 17 in vivo ablations performed in canine livers and 35 previously published ablations performed in porcine livers.
Ablation dimensions in the perfused model correlated well with corresponding in vivo ablations (R
= 0.9098) with a 95% confidence interval of < 2.2 mm. Additionally, the validated perfused model showed that the IRE ablation zone grew logarithmically with increasing pulse numbers, showing small difference in ablation size over 200-600 pulses (3.2 mm ± 3.8 width and 5.2 mm ± 3.9 height).
The perfused organ model provides an alternative to animal trials for investigation of IRE treatments. It may have an important role in the future development of new devices, algorithms, and techniques for this therapy.
Aims We report our experience with three generations of the Cardia patent foramen ovale (PFO) occluder in patients with cryptogenic thrombo-embolic events (TE). Methods and results Between 1998 and ...2004, interventional PFO closure was attempted in 403 patients. Prior to PFO closure, 605 TE occurred, translating into an annual incidence of 3.1%. PFO closure was successful in all patients. Peri-procedural complications occurred in eight patients (2.0%). At 6 months follow-up, residual shunt was present in 10.8% of patients. Transient thrombi developed on 10 devices (predominantly generation II) and asymptomatic wire fractures were detected in 14 cases (generation I and II). The annual incidence of recurrent TE was 2.0% (n=13). Atrial septal aneurysm and prior device-related thrombus formation were identified as predictors of recurrent TE. Conclusion Owing to technical improvements and modified adjunctive pharmacotherapy, the rate of thrombus formation has declined and wire fractures are virtually absent in generation III devices. The overall rate of recurrent TE is reduced by transcatheter PFO closure with the Cardia PFO occluder, and seems comparable to recurrence rates reported for other devices used for this purpose.
To report our experience in providing cardiac technician led paediatric echocardiography services in a district general hospital in the United Kingdom.
We have collected prospectively the numbers of ...referrals, and the proportion of abnormal echocardiograms, since inception of the service in 2000. In additional, for a period of 12 months, we have audited in detail the patterns of referral to the service, and outcomes, assessing the effect of the service on the outreach clinic run by a visiting paediatric cardiologist.
Use of the system resulted in detection of a wide range of abnormalities, with our audit showing that the patients received appropriate management. The total referrals to the service increased 10 fold over the 4 year period of the study. The proportion of abnormal hearts detected by echocardiography, however, dropped from 90 per cent to 16 per cent over the same period. The numbers of patients seen in the outreach cardiology clinic remained unaltered.
Having been proved to be an effective model for the triage of children with suspected congenital cardiac disease, adoption of a cardiac technician led echocardiographic service has seen a dramatic increase in the numbers of echocardiograms requested, without decreasing the workload of the visiting paediatric cardiologist.
Vibrio cholerae is a globally important pathogen that is endemic in many areas of the world and causes 3-5 million reported cases of cholera every year. Historically, there have been seven ...acknowledged cholera pandemics; recent outbreaks in Zimbabwe and Haiti are included in the seventh and ongoing pandemic. Only isolates in serogroup O1 (consisting of two biotypes known as 'classical' and 'El Tor') and the derivative O139 can cause epidemic cholera. It is believed that the first six cholera pandemics were caused by the classical biotype, but El Tor has subsequently spread globally and replaced the classical biotype in the current pandemic. Detailed molecular epidemiological mapping of cholera has been compromised by a reliance on sub-genomic regions such as mobile elements to infer relationships, making El Tor isolates associated with the seventh pandemic seem superficially diverse. To understand the underlying phylogeny of the lineage responsible for the current pandemic, we identified high-resolution markers (single nucleotide polymorphisms; SNPs) in 154 whole-genome sequences of globally and temporally representative V. cholerae isolates. Using this phylogeny, we show here that the seventh pandemic has spread from the Bay of Bengal in at least three independent but overlapping waves with a common ancestor in the 1950s, and identify several transcontinental transmission events. Additionally, we show how the acquisition of the SXT family of antibiotic resistance elements has shaped pandemic spread, and show that this family was first acquired at least ten years before its discovery in V. cholerae.
To investigate the histological, ultrastructural and immunohistochemical features of the vascular lining of dermal telangiectasia, a characteristic clinical finding in scleroderma.
Standard ...histological, electron microscopic and immunohistological techniques were used to examine dermal telangiectasias in five patients with limited scleroderma, the most common scleroderma variant in Caucasian populations.
The telangiectasias were dilated postcapillary venules located in the papillary and superficial reticular dermis. The vessel walls consisted of non-fenestrated endothelial cells surrounded by a variable number of pericytes and smooth muscle cells. There were no unique ultrastructural features. Thickened collagen fibres in the reticular or deep dermis were seen in all but one patient, although in variable and generally minimal quantities. Surrounding infiltrating inflammatory cells were scarce. No enhanced endothelial staining was obtained with antibodies directed against endoglin, endothelin, E-selectin and ICAM-1 suggesting a resting or inactivated state.
The immunohistological and ultrastructural features of the lining endothelium of established telangiectasias in long-standing, limited scleroderma appear benign. It would be of interest to examine telangiectasias in the early phase of their formation. Alternatively, other explanations need to be explored in understanding the aetiopathogenesis of telangiectasia in scleroderma.
Although pre-revascularization ischaemia testing is recommended, the interaction between the extent of ischaemia and myocardial scar with performance of revascularization on patient survival is ...unclear.
We identified 13 969 patients who underwent adenosine or exercise stress SPECT myocardial perfusion scintigraphy (MPS). The percent myocardium ischaemic (%I) and fixed (%F) were calculated using 5 point/20-segment MPS scoring. Patients lost to follow-up (2.8%) were excluded leaving 13 555 patients 35% with history (Hx) of known coronary artery disease (CAD), 65% exercise stress, 61% male, age 66 ± 12. Follow-up was performed at 12-18 months for early revascularization and at >7 years for all-cause death (ACD) (mean follow-up 8.7 ± 3.3 years). All-cause death was modelled using Cox proportional hazards modelling adjusting for logistic-based propensity scores, MPS, revascularization, and baseline characteristics. During FU, 3893 ACD (29%, 3.3%/year) and 1226 early revascularizations (9.0%) occurred. After risk-adjustment, a three-way interaction was present between %I, early revascularization, and HxCAD, such that %I identified a survival benefit with early revascularization in patients without prior myocardial infarction (MI), whereas no such benefit was present in patients with prior MI (overall model χ(2)= 3932, P < 0.001; interaction P < 0.021). Further modelling revealed that after excluding patients with scar >10% total myocardium, %I identified a survival benefit in all patients.
In this large observational series with long-term follow-up, patients with significant ischaemia and without extensive scar were likely to realize a survival benefit from early revascularization. In contrast, the survival of patients with minimal ischaemia was superior with medical therapy without early revascularization.
Single nucleotide polymorphisms (SNPs) are highly abundant, amendable to high-throughput genotyping, and useful for a number of breeding and genetics applications in crops. SNP frequencies vary ...depending on the species and populations under study, and therefore target SNPs need to be carefully selected to be informative for each application. While multiple SNP genotyping systems are available for rice (Oryza sativa L. and its relatives), they vary in their informativeness, cost, marker density, speed, flexibility, and data quality. In this study, we report the development and performance of the Cornell-IR LD Rice Array (C7AIR), a second-generation SNP array containing 7,098 markers that improves upon the previously released C6AIR. The C7AIR is designed to detect genome-wide polymorphisms within and between subpopulations of O. sativa, as well as O. glaberrima, O. rufipogon and O. nivara. The C7AIR combines top-performing SNPs from several previous rice arrays, including 4,007 SNPs from the C6AIR, 2,056 SNPs from the High Density Rice Array (HDRA), 910 SNPs from the 384-SNP GoldenGate sets, 189 SNPs from the 44K array selected to add information content for elite U.S. tropical japonica rice varieties, and 8 trait-specific SNPs. To demonstrate its utility, we carried out a genome-wide association analysis for plant height, employing the C7AIR across a diversity panel of 189 rice accessions and identified 20 QTLs contributing to plant height. The C7AIR SNP chip has so far been used for genotyping >10,000 rice samples. It successfully differentiates the five subpopulations of Oryza sativa, identifies introgressions from wild and exotic relatives, and is useful for quantitative trait loci (QTL) and association mapping in diverse materials. Moreover, data from the C7AIR provides valuable information that can be used to select informative and reliable SNP markers for conversion to lower-cost genotyping platforms for genomic selection and other downstream applications in breeding.
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