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PubMed2003

Dialysis, kidney transplantation, or pancreas transplantation for patients with diabetes mellitus and renal failure: a decision analysis of treatment options.

Patients with type 1 diabetes mellitus and end-stage renal disease may remain on dialysis or undergo cadaveric kidney transplantation, living kidney transplantation, sequential pancreas after living kidney transplantation, or simultaneous pancreas-kidney transplantation. It is unclear which of these options is most effective. The objective of this study was to determine the optimal treatment strategy for type 1 diabetic patients with renal failure using a decision analytic Markov model. Input data were obtained from the published medical literature, the United Network for Organ Sharing registry, and patient interviews. The outcome measures were life expectancy (in life-years [LY]) and quality-adjusted life expectancy (in quality-adjusted life-years [QALY]). Living kidney transplantation was associated with 18.30 LY and 10.29 QALY; pancreas after kidney transplantation, 17.21 LY and 10.00 QALY; simultaneous pancreas-kidney transplantation, 15.74 LY and 9.09 QALY; cadaveric kidney transplantation, 11.44 LY and 6.53 QALY; dialysis, 7.82 LY and 4.52 QALY. The results were sensitive to the value of several key variables. Simultaneous pancreas-kidney transplantation had the greatest life expectancy and quality-adjusted life expectancy when living kidney transplantation was excluded from the analysis. These data indicate that living kidney transplantation is associated with the greatest life expectancy and quality-adjusted life expectancy for type 1 diabetic patients with renal failure. Treatment strategies involving pancreas transplantation should be considered for patients with frequent metabolic complications of diabetes and for those patients who favor kidney-pancreas transplantation over kidney transplantation alone. For patients without a living donor, simultaneous pancreas-kidney transplantation is associated with the greatest life expectancy.

Adult↗

PubMed2005

Combined lung and liver transplantation: the United States experience.

BACKGROUND: Combined transplantation of the lungs and liver is indicated for patients who would not be expected to survive transplantation of either organ alone. No single center has accumulated a significant experience, and as a result the expectations for this operation in the current era are unknown. METHODS: Patients that have undergone combined lung-liver transplantation in the United States were enrolled through the United Network for Organ Sharing Organ Procurement and Transplantation Network database. In addition, the English-language literature was searched for additional cases of combined lung-liver transplantation. RESULTS: Eleven patients have undergone combined lung and liver transplantation in the United States at different centers. The 1- and 5-year patient survival rates are of 79% and 63%, respectively, and no patient has required retransplantation. These patient survival rates are equivalent to similar a combined lung-liver case series from the United Kingdom (P=0.37, log-rank test) and isolated orthotopic liver transplantation in the United States (P=0.59, log-rank test), and are comparable to patient survival rates following isolated lung transplantation in the United States. CONCLUSIONS: Patient survival of combined lung-liver transplantation is comparable to that of isolated liver and isolated bilateral lung transplantation. This option should be considered for patients with end-stage lung disease and liver disease when transplantation of a single organ transplantation is precluded by severe disease in the other organ system.

Adolescent↗

PubMed2006

Consensus by democracy. Using meta-analyses of microarray and genomic data to model the cold acclimation signaling pathway in Arabidopsis.

The whole-genome response of Arabidopsis (Arabidopsis thaliana) exposed to different types and durations of abiotic stress has now been described by a wealth of publicly available microarray data. When combined with studies of how gene expression is affected in mutant and transgenic Arabidopsis with altered ability to transduce the low temperature signal, these data can be used to test the interactions between various low temperature-associated transcription factors and their regulons. We quantized a collection of Affymetrix microarray data so that each gene in a particular regulon could vote on whether a cis-element found in its promoter conferred induction (+1), repression (-1), or no transcriptional change (0) during cold stress. By statistically comparing these election results with the voting behavior of all genes on the same gene chip, we verified the bioactivity of novel cis-elements and defined whether they were inductive or repressive. Using in silico mutagenesis we identified functional binding consensus variants for the transcription factors studied. Our results suggest that the previously identified ICEr1 (induction of CBF expression region 1) consensus does not correlate with cold gene induction, while the ICEr3/ICEr4 consensuses identified using our algorithms are present in regulons of genes that were induced coordinate with observed ICE1 transcript accumulation and temporally preceding genes containing the dehydration response element. Statistical analysis of overlap and cis-element enrichment in the ICE1, CBF2, ZAT12, HOS9, and PHYA regulons enabled us to construct a regulatory network supported by multiple lines of evidence that can be used for future hypothesis testing.

Acclimatization↗

PubMed2006

Does assisted reproduction technology, per se, increase the risk of preterm birth?

There is little doubt that all methods of assisted reproduction increase the likelihood of multiple pregnancy and, as a result, increase the likelihood of preterm birth. Data from the East Flanders Prospective Twin Study clearly show that the proportion of spontaneous to iatrogenic twins has changed from 25:1 to 1:1 over the past two decades. Data from the very low birthweight (VLBW) Infant Database of the Israel Neonatal Network showed that 10% of VLBW singletons were a result of assisted reproduction compared with 60% of the VLBW twins and 90% of the VLBW triplets. Irrespective of plurality, an association between preterm birth and assisted reproduction has long been suspected and was related to causes such as iatrogenic preterm birth (in the so-called 'premium' pregnancies), fertility history, past obstetric performance and to underlying medical conditions of the female partner. With more data available, a clearer picture is defined. Two different, recent meta-analyses showed that singleton pregnancies resulting from in vitro fertilisation (IVF) have increased rates of preterm birth at <33 weeks of gestation (OR 2.99; 95% CI 1.54-5.80), at <37 weeks of gestation (OR 1.93; 95% CI 1.36-2.74) and a relative risk of 1.98 (95% CI 1.77-2.22) for preterm birth in singleton pregnancies resulting from in vitro fertilisation embryo transfer/gamete intra fallopian transfer (IVF-ET/GIFT) compared with naturally conceived pregnancies. Since there is no way to predict which pregnant woman is at increased risk of preterm birth, it may be advisable to consider all pregnancies after assisted reproduction as being at risk. In any case, the most appropriate endpoint after assisted reproduction should also include preterm or term birth as measure of success.

Female↗

PubMedDate not supplied

Applications of evidence-based medicine: cranial cruciate ligament injury repair in the dog.

OBJECTIVE: To evaluate the literature reporting surgical interventions pertaining to canine cranial cruciate ligament (CCL) injury using an evidence-based medicine paradigm. STUDY DESIGN: Systematic literature review. METHODS: An on-line bibliographic search through Medline, PubMed, Veterinary Information Network, and Commonwealth Agricultural Bureau Abstracts was performed during August 2004. Two hundred and forty resources of information were identified. Studies were compared and evaluated with regard to study design (retrospective, prospective, randomization), surgical technique, short- and long-term follow-up, and evidence classification. RESULTS: Twenty-eight resources qualified to assist with evidence classification. No class I or class II studies were present, 5 studies were categorized as a class III and 23 studies were categorized as a class IV. Seventeen studies were retrospectively designed and 11 studies were prospectively designed. Proposed results ranged from a wide variety of subjective findings including clinical impression, radiographic analysis, synovial fluid analysis, gross pathology, and histopathology. Objective results, although infrequent, included force plate analysis and cadaveric biomechanical testing. CONCLUSIONS: At this time, the application of evidence-based medicine in analyzing the current available evidence suggests that there is not a single surgical procedure that has enough data to recommend that it can consistently return dogs to normal function after CCL injury. The requirement for assessing and categorizing the available evidence becomes increasingly important as more data becomes available and the quality of research improves. CLINICAL RELEVANCE: An evidence-based medicine paradigm did not provide sufficient evidence favoring 1 surgical technique for management of canine CCL injury.

Animals↗

PubMed2006

Clinical effectiveness of treatment with hyperbaric oxygen for neonatal hypoxic-ischaemic encephalopathy: systematic review of Chinese literature.

OBJECTIVES: To investigate the clinical effectiveness of treatment with hyperbaric oxygen for neonates with hypoxic-ischaemic encephalopathy. This treatment is frequently used in China but much less often in the West. DATA SOURCES: Western (Cochrane controlled trials register and database of systematic reviews, Medline, Embase, CINAHL, and HealthSTAR) and Chinese (China Hospital Digital Library, Chinese Medical Journal Network) databases and hand search of Chinese journals. No language restrictions. REVIEW METHODS: Randomised or quasi-randomised controlled trials of treatment with hyperbaric oxygen compared with "usual care" in term neonates with hypoxic-ischaemic encephalopathy. Outcomes included mortality and long term neurological sequelae. Standardised forms were used to extract and compare data. Criteria of York Centre for Reviews and Dissemination were used to assess quality. Analysis was mainly qualitative but included meta-analysis. RESULTS: 20 trials were found, mainly from Chinese sources. The reporting quality of trials was poor by Western (CONSORT) standards. Treatment with hyperbaric oxygen had better outcomes than the comparator in almost all trials. The odds ratios of the meta-analyses were 0.26 (95% confidence interval 0.14 to 0.46) for mortality and 0.41 (0.27 to 0.61) for neurological sequelae. CONCLUSION: Treatment with hyperbaric oxygen possibly reduces mortality and neurological sequelae in term neonates with hypoxic-ischaemic encephalopathy. Because of the poor quality of reporting in all trials and the possibility of publication bias, an adequately powered, high quality randomised controlled trial is needed to investigate these findings. The Chinese medical literature may be a rich source of evidence to inform clinical practice and other systematic reviews.

China↗

PubMed2006

Topological and functional discovery in a gene coexpression meta-network of gastric cancer.

Gastric cancer is a leading cause of global cancer mortality, but comparatively little is known about the cellular pathways regulating different aspects of the gastric cancer phenotype. To achieve a better understanding of gastric cancer at the levels of systems topology, functional modules, and constituent genes, we assembled and systematically analyzed a consensus gene coexpression meta-network of gastric cancer incorporating >300 tissue samples from four independent patient populations (the "gastrome"). We find that the gastrome exhibits a hierarchical scale-free architecture, with an internal structure comprising multiple deeply embedded modules associated with diverse cellular functions. Individual modules display distinct subtopologies, with some (cellular proliferation) being integrated within the primary network, and others (ribosomal biosynthesis) being relatively isolated. One module associated with intestinal differentiation exhibited a remarkably high degree of autonomy, raising the possibility that its specific topological features may contribute towards the frequent occurrence of intestinal metaplasia in gastric cancer. At the single-gene level, we discovered a novel conserved interaction between the PLA2G2A prognostic marker and the EphB2 receptor, and used tissue microarrays to validate the PLA2G2A/EphB2 association. Finally, because EphB2 is a known target of the Wnt signaling pathway, we tested and provide evidence that the Wnt pathway may also similarly regulate PLA2G2A. Many of these findings were not discernible by studying the single patient populations in isolation. Thus, besides enhancing our knowledge of gastric cancer, our results show the broad utility of applying meta-analytic approaches to genome-wide data for the purposes of biological discovery.

Cluster Analysis↗

PubMed2004

The effects of position on oxygen saturation in acute stroke: a systematic review.

OBJECTIVE: To investigate the effect of body position on oxygen saturation in the acute stages post stroke. DESIGN: Systematic review. METHODS: Databases: PREMEDLINE and MEDLINE, Psychinfo, EMBASE, CINAHL, PEDro, all EBM Reviews and Scottish Intercollegiate Guidelines Network (SIGN). KEYWORDS: combinations of cerebrovascular accident/stroke/hemiplegia/ cerbrovascular disorders and position or posture or sitting or standing/lying/supine/ side lying, with oxygen saturation/oxygen levels/blood gas analysis/hypoxia/sleep apnea syndrome/obstructive sleep disorder/Cheyne Stokes breathing. LIMITS: English language, human, adults and clinical trials. The quality of relevant papers was independently reviewed using criteria based on the SIGN guidelines for randomized controlled trials and methods described by Rywdik et al. RESULTS: There were four relevant studies involving 183 patients: three high quality and one poor quality. Heterogeneity in the testing positions, selection criteria, outcome measures and analysis methods prevented meta-analysis. There was strong evidence that body position did not affect oxygen saturation in acute stroke patients without relevant (respiratory) co-morbidities. There was limited evidence that sitting in a chair had a beneficial effect and lying positions had a deleterious effect on oxygen saturation in acute stroke patients with respiratory co-morbidities. CONCLUSIONS: Acute stroke patients without respiratory co-morbidities can adopt any body position, people with respiratory co-morbidities should be positioned as upright as possible.

Blood Gas Analysis↗

PubMed2026

Health risk assessment of inorganic arsenic: an umbrella review.

Inorganic arsenic (iAs) is a toxic environmental pollutant linked to serious health risks, prompting global regulatory efforts. This study identifies major health conditions associated with iAs exposure using text network analysis, and assesses health risk assessments through an umbrella review and dose-response analysis. It synthesizes previous systematic reviews to offer a broader perspective on iAs-related health effects. An optimized text network analysis-based search strategy was applied across multiple databases to identify relevant systematic reviews. An umbrella review framework was employed to synthesize and reinterpret findings across systematic reviews. The methodological quality of included systematic reviews was assessed using the A MeaSurement Tool to Assess systematic Reviews 2 tool. Extracted data on study characteristics, exposure levels, and risk estimates were analyzed to evaluate the dose-response relationship between iAs exposure and health outcomes. From 922 systematic reviews, 36 were included and categorized into 10 health condition groups. For example, seven SRs found a significant dose-response relationship between iAs and bladder cancer, with one systematic review reporting relative risks of 2.70, 4.20, and 5.80 at 10, 50, and 150 µg/L, respectively. Individual study analysis further showed that each 10 µg/L increase in iAs raised bladder cancer risk by 3.11 % (p=0.003). iAs exposure is associated with hypertension, diabetes, cardiovascular disease, and adverse fetal outcomes. Dose-dependent increases in bladder cancer, lung cancer, and hypertension risks were observed. These findings support more precise health risk assessments and regulatory strategies.

Humans↗

PubMed1992

The impact of stressful life events and social support on drinking among older adults: a general population survey.

This article is an analysis of stressful life events, the buffering hypothesis, and alcohol use in a national sample of 1,418 respondents 60 years of age and over. The results indicate that older adults who experience stressful losses are significantly more likely to drink excessively than those who have not experienced such losses or who have experienced them to a lesser extent. Increased drinking among older adults may therefore be a reaction to life circumstances in which alcohol represents an attempt to cope with traumatic loss, personal as well as within the kinship network. Supportive resources of spouse, family, friends, and church appear to have a stress-buffering effects that reduces the excessive-drinking response to life crisis. Data suggest, however, that older persons are vulnerable to the magnitude of losses experienced as they grow older and lose more of their family, friends, and peers. These stressors appear to seriously impact their drinking behavior and are not effectively buffered. Respondents report that drinking may increase during periods of prolonged exposure to emotionally depleting life change and loss, when supportive needs may exceed the capacities of personal and social support resources.

Adaptation, Psychological↗

PubMed2005

Clinical effectiveness and cost-effectiveness of immediate angioplasty for acute myocardial infarction: systematic review and economic evaluation.

OBJECTIVES: To review the clinical evidence comparing immediate angioplasty with thrombolysis, and to consider whether it would be cost-effective. DATA SOURCES: Electronic databases. Experts in the field. REVIEW METHODS: For clinical effectiveness, a comprehensive review of randomised control trials (RCTs) was used for efficacy, and a selection of observational studies such as case series or audit data used for effectiveness in routine practice. RCTs of thrombolysis were used to assess the relative value of prehospital and hospital thrombolysis. Observational studies were used to assess the representativeness of patients in the RCTs, and to determine whether different groups have different capacity to benefit. Clinical effectiveness was synthesised through a narrative review with full tabulation of results of all included studies and a meta-analysis to provide a precise estimate of absolute clinical benefit. Consideration was given to the effect of the growing use of stents. The economic modelling adopted an NHS perspective to develop a decision-analytical model of cost-effectiveness focusing on opportunity costs over the short term (6 months). RESULTS: The results were consistent in showing an advantage of immediate angioplasty over hospital thrombolysis. The updated meta-analysis showed that mortality is reduced by about one-third, from 7.6% to 4.9% in the first 6 months, and by about the same in studies of up to 24 months. Reinfarction is reduced by over half, from 7.6% to 3.1%. Stroke is reduced by about two-thirds, from 2.3% with thrombolysis to 0.7% with percutaneous coronary intervention (PCI), with the difference being due to haemorrhagic stroke. The need for coronary artery bypass graft is reduced by about one-third, from 13.2% to 8.4%. Caution is needed in interpreting some of the older trials, as changes such as an increase in stenting and the use of the glycoprotein IIb/IIa inhibitors may improve the results of PCI. There is little evidence comparing prehospital thrombolysis with immediate PCI. Research on thrombolysis followed by PCI, known as 'facilitated PCI', is underway, but results are not yet available. Trials may be done in select centres and results may not be as good in lower volume centres, or out of normal working hours. In addition, much of the marginal mortality benefit of PCI over hospital thrombolysis may be lost if door-to-balloon time were more than an hour longer than door-to-needle time. Conversely, within the initial 6 hours, the later patients present, the greater the relative advantage of PCI. Results suggest that PCI is more cost-effective than thrombolysis, providing additional benefits in health status at some extra cost. In the longer term, the cost difference is expected to be reduced because of higher recurrence and reintervention rates among those who had thrombolysis. CONCLUSIONS: If both interventions were routinely available, the economic analysis favours PCI, given the assumptions of the model. However, very few units in England could offer a routine immediate PCI service at present, and there would be considerable resource implications of setting up such services. Without a detailed survey of existing provision, it is not possible to quantify the implications, but they include both capital and revenue: an increase in catheter laboratory provision and running costs. The greatest problem would be staffing, and that would take some years to resolve. A gradual incrementalist approach based on clinical networks, with transfer to centres able to offer PCI, may be used. In rural areas, one option may be to promote an increase in prehospital thrombolysis, with PCI for thrombolysis failures. There is a need for data on the long-term consequences of treatment, the quality of life of patients after treatment, and the effects of PCI following thrombolysis failure.

Angioplasty↗

PubMed2005

Genetic networks controlling retinal injury.

PURPOSE: The present study defines genomic loci underlying coordinate changes in gene expression following retinal injury. METHODS: A group of acute phase genes expressed in diverse nervous system tissues was defined by combining microarray results from injury studies from rat retina, brain, and spinal cord. Genomic loci regulating the brain expression of acute phase genes were identified using a panel of BXD recombinant inbred (RI) mouse strains. Candidate upstream regulators within a locus were defined using single nucleotide polymorphism databases and promoter motif databases. RESULTS: The acute phase response of rat retina, brain, and spinal cord was dominated by transcription factors. Three genomic loci control transcript expression of acute phase genes in brains of BXD RI mouse strains. One locus was identified on chromosome 12 and was highly correlated with the expression of classic acute phase genes. Within the locus we identified the inhibitor of DNA binding 2 (Id2) as a candidate upstream regulator. Id2 was upregulated as an acute phase transcript in injury models of rat retina, brain, and spinal cord. CONCLUSIONS: We defined a group of transcriptional changes associated with the retinal acute injury response. Using genetic linkage analysis of natural transcript variation, we identified regulatory loci and candidate regulators that control transcript levels of acute phase genes.

Acute-Phase Proteins↗

PubMed1994

Multifactorial analysis of renal transplants reported to the United Network for Organ Sharing Registry: a 1994 update.

1. From a multivariate log-linear analysis of 57,303 renal transplants between 1988 and 1994, the top 10 factors influencing one-year and 3-year cadaveric graft survival rates were ranked as follows: [table: see text] 2. Center effects accounted for 30% and 28% of all assignable variations in one-year and 3-year outcomes, respectively. Although center variation dominated 32 other variables, most factors were relatively independent of transplant center. 3. Novel to our own multifactorial analyses of the UNOS Kidney Transplant Registry were 6 pretransplant factors (recipient pretransplant dialysis, pregnancy, PRA technique, donor disposition and preservation, and ABO compatibility). Survival rates over the various combinations of these new factors were not significantly different. 4. For the first time in our multivariate analyses, 4 posttransplantation factors (delayed graft function, rejection episodes prior to discharge, induction and maintenance drug therapies) were included in the log-linear model. It is noteworthy that graft survival in both transplant periods was seriously imperiled following delayed graft function or rejection prior to discharge, yet the accounting for these pseudo-outcome variables did not alter the influence of the remaining 31 transplant factors. Finally, maintenance drug therapies strongly influenced short-term outcomes but did not influence long-term results, except for a noteworthy trend toward increased survival rates for FK506 therapy.

Adolescent↗

PubMed1994

Managed care plan performance since 1980. A literature analysis.

OBJECTIVE: To compare the health care utilization, expenditure, quality of care, and satisfaction since 1980 of enrollees in managed care and indemnity plans. DATA SOURCES AND STUDY SELECTION: Studies selected met the following criteria: data from 1980 forward, private insurance or Medicare enrollees, a comparison group, a reasonable attempt at statistical adjustment for noncomparable managed care and indemnity plan enrollees, and peer-reviewed findings (with two exceptions). Few studies on preferred provider organization plan performance met the selection criteria. DATA SYNTHESIS: Compared with indemnity plans, health maintenance organization plans had somewhat lower hospital admission rates, 1% to 20% shorter hospital length of stay, the same or more physician office visits per enrollee, less use of expensive procedures and tests, greater use of preventive services, mixed results on outcomes, and somewhat lower enrollee satisfaction with services but higher satisfaction with costs. The evidence does not support the hypothesis that prepaid group practice or staff model health maintenance organizations are more effective than individual practice association or network model health maintenance organizations. CONCLUSIONS: Although this literature analysis found several clear patterns of results, several factors, including unmeasured selection bias, diverse and rapidly changing health plans and local market conditions, and relatively few research results, suggest that generalizations must be made with caution.

Health Care Costs↗

PubMed1998

[Economic and organizational evaluation of an imaging network (PACS)].

OBJECTIVE: Over the last twenty years, imaging modalities featuring new image production methods (ultrasound, nuclear magnetic resonance, etc.) have appeared on the market. Nevertheless, conventional radiology still accounts for 70% of the image examinations carried out in most western countries, including France. The conventional radiological image is in the process of evolving from analog to digital form. Digitalization of radiology means that image acquisition, archiving and distribution functions that were previously carried out by hand can now be automated using a Picture Archiving and Communication System. Decision-makers are having to decide whether or not to promote the development of PACS which, while they considerably modernize the way in which images are managed, also require heavy capital outlays. METHOD: A critical appraisal of the literature allowed us to evaluate the relative cost and the efficiency of these image networks in comparison with film-based archiving and communication systems. RESULTS: It is clear from the economic evaluation that a PACS strategy involves greater costs than a film system. While PACS systems do generate savings on film and on storage space and obviate the need for certain staff, these savings do not offset the extra equipment and maintenance costs. This situation is likely to persist for some years yet, even when future price reductions are taken into account. The objective of this new radiological information management method is to improve organizational efficiency and hospital productivity. However, the economic evaluations that have been published to date are cost studies which do not take the efficiency criterion into account. A number of potential organizational benefits such as the fact that medical decisions can be made more quickly or that the average length of hospital stays can be reduced, are often claimed for PACS. However, for methodological reasons, these results cannot be generalised to cover all PACS. It is difficult to compare PACS and film systems because the PACS technology is continuously evolving and because each PACS is specific to a site. CONCLUSION: After having weighted these different points, the ANAES has made the following recommendations concerning the development of PACS. A strategic analysis should be carried out before any decision is made to install a PACS. Moreover, hospitals will have to define the precise functions of their PACS in relation to the objectives of their medical project and each network must be configurated coherently.

Analog-Digital Conversion↗