Chapter 3: Choosing the Important Outcomes for a Systematic Review of a Medical Test

In this chapter of the Evidence-based Practice Centers Methods Guide for Medical Tests, we describe how the decision to use a medical test generates a broad range of outcomes and that each of these outcomes should be considered for inclusion in a systematic review. Awareness of these varied outcomes affects how a decision maker balances the benefits and risks of the test; therefore, a systematic review should present the evidence on these diverse outcomes. The key outcome categories include clinical management outcomes and direct health effects; emotional, social, cognitive, and behavioral responses to testing; legal and ethical outcomes, and costs. We describe the challenges of incorporating these outcomes in a systematic review, suggest a framework for generating potential outcomes for inclusion, and describe the role of stakeholders in choosing the outcomes for study. Finally, we give examples of systematic reviews that either included a range of outcomes or that might have done so. The following are the key messages in this chapter: Consider both the outcomes that are relevant to the process of testing and those that are relevant to the results of the test.Consider inclusion of outcomes in all five domains: clinical management effects, direct test effects; emotional, social, cognitive and behavioral effects; legal and ethical effects, and costs.Consider to which group the outcomes of testing are most relevant.Given resource limitations, prioritize which outcomes to include. This decision depends on the needs of the stakeholder(s), who should be assisted in prioritizing the outcomes for inclusion

The Dawn of Open Access to Phylogenetic Data

The scientific enterprise depends critically on the preservation of and open access to published data. This basic tenet applies acutely to phylogenies (estimates of evolutionary relationships among species). Increasingly, phylogenies are estimated from increasingly large, genome-scale datasets using increasingly complex statistical methods that require increasing levels of expertise and computational investment. Moreover, the resulting phylogenetic data provide an explicit historical perspective that critically informs research in a vast and growing number of scientific disciplines. One such use is the study of changes in rates of lineage diversification (speciation - extinction) through time. As part of a meta-analysis in this area, we sought to collect phylogenetic data (comprising nucleotide sequence alignment and tree files) from 217 studies published in 46 journals over a 13-year period. We document our attempts to procure those data (from online archives and by direct request to corresponding authors), and report results of analyses (using Bayesian logistic regression) to assess the impact of various factors on the success of our efforts. Overall, complete phylogenetic data for ~60% of these studies are effectively lost to science. Our study indicates that phylogenetic data are more likely to be deposited in online archives and/or shared upon request when: (1) the publishing journal has a strong data-sharing policy; (2) the publishing journal has a higher impact factor, and; (3) the data are requested from faculty rather than students. Although the situation appears dire, our analyses suggest that it is far from hopeless: recent initiatives by the scientific community -- including policy changes by journals and funding agencies -- are improving the state of affairs

Multilocus Short Sequence Repeat Analysis of Mycobacterium avium subsp. paratuberculosis Isolates from Dairy Herds in Northeastern United States of a Longitudinal Study Indicates Low Shedders are Truly Infected

ABSTRACT The objectives of this study were to evaluate whether low shedders of Mycobacterium avium subsp. paratuberculosis (MAP) were pass-through animals or whether they were truly infected. We also evaluated whether these animals were possibly infected by the supershedders. The MAP isolates were obtained from a longitudinal study that involved three different herds in the northeastern US. The shedding levels of animals at each culturepositive occasion were determined. Selected isolates were collected from all animals that were culture-positive at the same time super-shedders were present in the herds and from super-shedders. Using a multilocus short sequence repeat (MLSSR) approach we found 15 different strains from a total of 142 isolates analyzed. The results indicated herd-specific infections; a clonal infection in herd C with 89% of animals sharing the same strain, different strains in herds A and B. In herd C, 100% and in herd A, 17 to 70% of cows shed the same strain as that of contemporary super-shedders at a given collection date. About 82% of available tissue samples were culture-positive indicating a true infection. Taken together the results of MAP strain-typing and shedding levels, we conclude that at least 50% of low shedders have same strain as that of a contemporary super-shedder. The results of this study indicate that very few cows had characteristics of a possible pass-through animal; many more cows were actively infected. The sharing of same strain of low shedders with the contemporary super-shedders suggests that low shedders may be infected as adults by the super-shedders

Adenosine A2A receptor modulation of hippocampal CA3-CA1 synapse plasticity during associative learning in behaving mice

© 2009 Nature Publishing Group All rights reservedPrevious in vitro studies have characterized the electrophysiological and molecular signaling pathways of adenosine tonic modulation on long-lasting synaptic plasticity events, particularly for hippocampal long-term potentiation(LTP). However, it remains to be elucidated whether the long-term changes produced by endogenous adenosine in the efficiency of synapses are related to those required for learning and memory formation. Our goal was to understand how endogenous activation of adenosine excitatory A2A receptors modulates the associative learning evolution in conscious behaving mice. We have studied here the effects of the application of a highly selective A2A receptor antagonist, SCH58261, upon a well-known associative learning paradigm - classical eyeblink conditioning. We used a trace paradigm, with a tone as the conditioned stimulus (CS) and an electric shock presented to the supraorbital nerve as the unconditioned stimulus(US). A single electrical pulse was presented to the Schaffer collateral–commissural pathway to evoke field EPSPs (fEPSPs) in the pyramidal CA1 area during the CS–US interval. In vehicle-injected animals, there was a progressive increase in the percentage of conditioning responses (CRs) and in the slope of fEPSPs through conditioning sessions, an effect that was completely prevented (and lost) in SCH58261 (0.5 mg/kg, i.p.)-injected animals. Moreover, experimentally evoked LTP was impaired in SCH58261- injected mice. In conclusion, the endogenous activation of adenosine A2A receptors plays a pivotal effect on the associative learning process and its relevant hippocampal circuits, including activity-dependent changes at the CA3-CA1 synapse.This study was supported by grants from the Spanish Ministry of Education and Research (BFU2005-01024 and BFU2005-02512), Spanish Junta de Andalucía (BIO-122 and CVI-02487), and the Fundación Conocimiento y Cultura of the Pablo de Olavide University (Seville, Spain).B. Fontinha was in receipt of a studentship from a project grant (POCI/SAU-NEU/56332/2004) supported by Fundação para a Ciência e Tecnologia (FCT, Portugal), and of an STSM from Cost B30 concerted action of the EU

TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors.

The genomic regulatory programmes that underlie human organogenesis are poorly understood. Pancreas development, in particular, has pivotal implications for pancreatic regeneration, cancer and diabetes. We have now characterized the regulatory landscape of embryonic multipotent progenitor cells that give rise to all pancreatic epithelial lineages. Using human embryonic pancreas and embryonic-stem-cell-derived progenitors we identify stage-specific transcripts and associated enhancers, many of which are co-occupied by transcription factors that are essential for pancreas development. We further show that TEAD1, a Hippo signalling effector, is an integral component of the transcription factor combinatorial code of pancreatic progenitor enhancers. TEAD and its coactivator YAP activate key pancreatic signalling mediators and transcription factors, and regulate the expansion of pancreatic progenitors. This work therefore uncovers a central role for TEAD and YAP as signal-responsive regulators of multipotent pancreatic progenitors, and provides a resource for the study of embryonic development of the human pancreas

A study of 54 cases of left displacement of the abomasum: February to July 2005

Fifty-four cows with left displacement of the abomasum (LDA) submitted to the hospital facility at Riverview Veterinary Clinic from February to July 2005 were treated by right flank laparotomy and omentopexy. Five cows died (a survival rate 90.7%) and one cow (1.8%) was culled due to recurrence of the LDA post-operatively. Forty-one cows (76%) returned to good production post-operatively. Thirty-nine cows (72%) were pregnant six months after corrective surgery

IMPACT OF ROUX-EN-Y GASTRIC BYPASS SURGERY (RYGB) ON METABOLIC SYNDROME COMPONENTS AND ON THE USE OF ASSOCIATED DRUGS IN OBESE PATIENTS

ABSTRACT BACKGROUND The prevalence of obesity and metabolic syndrome is increasing worldwide and both behavior modification and drug therapy have low adherence. Gastric bypass has shown effective results in both reducing weight and improving comorbidities. OBJECTIVE To evaluate the impact of Roux-en-Y Gastric Bypass Surgery (RYGB) on both metabolic syndrome components and the use of associated drugs in obese patients. METHODS Historical cohort of patients subjected to Roux-en-Y Gastric Bypass Surgery (RYGB) between January 2007 and March 2014 in a private clinic. The sample consisted of 273 obese class II and III individuals, 86.4% of whom were female, with age ≥20 years, followed up for 2 months after surgery. Sociodemographic, anthropometric, biochemical, clinical, and drug-use data were collected from patients’ medical records. RESULTS Significant differences were found in weight, body mass index and waist circumference, after 60 postoperative days. Components for metabolic syndrome diagnosis (hypertension P=0.001; hyperglycemia P<0.001; hypertriglyceridemia P=0.006) were reduced after 60 days of postoperative, with the exception HDL-c (P=0.083). There was a significant reduction in the use of antihypertensive (P<0.001), hypoglycemic (P=0.013), lipid lowering (P<0.001), and antiobesity (P=0.010) drugs and increased use of gastroprotective drugs, vitamins, and minerals (P<0.001) after 60 postoperative days. CONCLUSION Patients subjected to Roux-en-Y Gastric Bypass Surgery exhibited both weight loss and significant improvement not only in metabolic syndrome components (except for HDL-c) but in the use of drugs associated with obesity and metabolic syndrome

Protective and risk factors in amateur equestrians and description of injury patterns: A retrospective data analysis and a case - control survey

Background In Switzerland there are about 150,000 equestrians. Horse related injuries, including head and spinal injuries, are frequently treated at our level I trauma centre. Objectives To analyse injury patterns, protective factors, and risk factors related to horse riding, and to define groups of safer riders and those at greater risk Methods We present a retrospective and a case-control survey at conducted a tertiary trauma centre in Bern, Switzerland. Injured equestrians from July 2000 - June 2006 were retrospectively classified by injury pattern and neurological symptoms. Injured equestrians from July-December 2008 were prospectively collected using a questionnaire with 17 variables. The same questionnaire was applied in non-injured controls. Multiple logistic regression was performed, and combined risk factors were calculated using inference trees. Results Retrospective survey A total of 528 injuries occured in 365 patients. The injury pattern revealed as follows: extremities (32%: upper 17%, lower 15%), head (24%), spine (14%), thorax (9%), face (9%), pelvis (7%) and abdomen (2%). Two injuries were fatal. One case resulted in quadriplegia, one in paraplegia. Case-control survey 61 patients and 102 controls (patients: 72% female, 28% male; controls: 63% female, 37% male) were included. Falls were most frequent (65%), followed by horse kicks (19%) and horse bites (2%). Variables statistically significant for the controls were: Older age (p = 0.015), male gender (p = 0.04) and holding a diploma in horse riding (p = 0.004). Inference trees revealed typical groups less and more likely to suffer injury. Conclusions Experience with riding and having passed a diploma in horse riding seem to be protective factors. Educational levels and injury risk should be graded within an educational level-injury risk index

Pre-Columbian land use in the ring-ditch region of the Bolivian Amazon

The nature and extent of pre-Columbian (pre-1492 AD) human impact in Amazonia is a contentious issue. The Bolivian Amazon has yielded some of the most impressive evidence for large and complex pre-Columbian societies in the Amazon basin, yet there remains relatively little data concerning the land use of these societies over time. Palaeoecology, when integrated with archaeological data, has the potential to fill these gaps in our knowledge. We present a 6,000-year record of anthropogenic burning, agriculture and vegetation change, from an oxbow lake located adjacent to a pre-Columbian ring-ditch in north-east Bolivia (13°15’44” S, 63°42’37” W). Human occupation around the lake site is inferred from pollen and phytoliths of maize (Zea mays L.) and macroscopic charcoal evidence of anthropogenic burning. First occupation around the lake was radiocarbon dated to ~2500 years BP. The persistence of maize in the record from ~1850 BP suggests that it was an important crop grown in the ringditch region in pre-Columbian times, and abundant macroscopic charcoal suggests that pre-Columbian land management entailed more extensive burning of the landscape than the slash-and-burn agriculture practised around the site today. The site was occupied continuously until near-modern times, although there is evidence for a decline in agricultural intensity or change in land use strategy, and possible population decline, from ~600-500 BP. The long and continuous occupation, which predates the establishment of rainforest in the region, suggests that pre-Columbian land use may have had a significant influence on ecosystem development at this site over the last ~2000 years