414 research outputs found

    Identifying future models for delivering genetic services: a nominal group study in primary care

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    BACKGROUND: To enable primary care medical practitioners to generate a range of possible service delivery models for genetic counselling services and critically assess their suitability. METHODS: Modified nominal group technique using in primary care professional development workshops. RESULTS: 37 general practitioners in Wales, United Kingdom too part in the nominal group process. The practitioners who attended did not believe current systems were sufficient to meet anticipated demand for genetic services. A wide range of different service models was proposed, although no single option emerged as a clear preference. No argument was put forward for genetic assessment and counselling being central to family practice, neither was there a voice for the view that the family doctor should become skilled at advising patients about predictive genetic testing and be able to counsel patients about the wider implications of genetic testing for patients and their family members, even for areas such as common cancers. Nevertheless, all the preferred models put a high priority on providing the service in the community, and often co-located in primary care, by clinicians who had developed expertise. CONCLUSION: There is a need for a wider debate about how healthcare systems address individual concerns about genetic concerns and risk, especially given the increasing commercial marketing of genetic tests

    The clinical features of the piriformis syndrome: a systematic review

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    Piriformis syndrome, sciatica caused by compression of the sciatic nerve by the piriformis muscle, has been described for over 70 years; yet, it remains controversial. The literature consists mainly of case series and narrative reviews. The objectives of the study were: first, to make the best use of existing evidence to estimate the frequencies of clinical features in patients reported to have PS; second, to identify future research questions. A systematic review was conducted of any study type that reported extractable data relevant to diagnosis. The search included all studies up to 1 March 2008 in four databases: AMED, CINAHL, Embase and Medline. Screening, data extraction and analysis were all performed independently by two reviewers. A total of 55 studies were included: 51 individual and 3 aggregated data studies, and 1 combined study. The most common features found were: buttock pain, external tenderness over the greater sciatic notch, aggravation of the pain through sitting and augmentation of the pain with manoeuvres that increase piriformis muscle tension. Future research could start with comparing the frequencies of these features in sciatica patients with and without disc herniation or spinal stenosis

    Early In-Hospital Mortality following Trainee Doctors' First Day at Work

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    BACKGROUND:There is a commonly held assumption that early August is an unsafe period to be admitted to hospital in England, as newly qualified doctors start work in NHS hospitals on the first Wednesday of August. We investigate whether in-hospital mortality is higher in the week following the first Wednesday in August than in the previous week. METHODOLOGY:A retrospective study in England using administrative hospital admissions data. Two retrospective cohorts of all emergency patients admitted on the last Wednesday in July and the first Wednesday in August for 2000 to 2008, each followed up for one week. PRINCIPAL FINDINGS:The odds of death for patients admitted on the first Wednesday in August was 6% higher (OR 1.06, 95% CI 1.00 to 1.15, p=0.05) after controlling for year, gender, age, socio-economic deprivation and co-morbidity. When subdivided into medical, surgical and neoplasm admissions, medical admissions admitted on the first Wednesday in August had an 8% (OR 1.08, 95% CI 1.01 to 1.16, p=0.03) higher odds of death. In 2007 and 2008, when the system for junior doctors' job applications changed, patients admitted on Wednesday August 1(st) had 8% higher adjusted odds of death than those admitted the previous Wednesday, but this was not statistically significant (OR 1.08, 95% CI 0.95 to 1.23, p=0.24). CONCLUSIONS:We found evidence that patients admitted on the first Wednesday in August have a higher early death rate in English hospitals compared with patients admitted on the previous Wednesday. This was higher for patients admitted with a medical primary diagnosis

    Cytomegalovirus Infection of the Colon Presenting as a Mass-Like Lesion

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    Cytomegalovirus (CMV) is responsible for the most common opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS). The colon is a common site for these infections in patients positive for human immunodeficiency virus. CMV rarely presents as an intraluminal inflammatory mass in the colon. Here we report the case of a CMV infection presenting as a mass-like lesion in an AIDS patient. The clinical diagnosis of CMV infection is largely based on the characteristic endoscopic appearance. Endoscopic procedures are encouraged early in the course of CMV infection in immunocompromised patients. CMV pseudotumors along with malignancy should be part of the endoscopic evaluation in patients with AIDS

    Defects in the Outer Limiting Membrane Are Associated with Rosette Development in the Nrl−/− Retina

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    The neural retinal leucine zipper (Nrl) knockout mouse is a widely used model to study cone photoreceptor development, physiology, and molecular biology in the absence of rods. In the Nrl−/− retina, rods are converted into functional cone-like cells. The Nrl−/− retina is characterized by large undulations of the outer nuclear layer (ONL) commonly known as rosettes. Here we explore the mechanism of rosette development in the Nrl−/− retina. We report that rosettes first appear at postnatal day (P)8, and that the structure of nascent rosettes is morphologically distinct from what is seen in the adult retina. The lumen of these nascent rosettes contains a population of aberrant cells protruding into the subretinal space that induce infolding of the ONL. Morphologically adult rosettes do not contain any cell bodies and are first detected at P15. The cells found in nascent rosettes are photoreceptors in origin but lack inner and outer segments. We show that the adherens junctions between photoreceptors and Müller glia which comprise the retinal outer limiting membrane (OLM) are not uniformly formed in the Nrl−/− retina and thus allow protrusion of a population of developing photoreceptors into the subretinal space where their maturation becomes delayed. These data suggest that the rosettes of the Nrl−/− retina arise due to defects in the OLM and delayed maturation of a subset of photoreceptors, and that rods may play an important role in the proper formation of the OLM

    Retinoblastoma Loss Modulates DNA Damage Response Favoring Tumor Progression

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    Senescence is one of the main barriers against tumor progression. Oncogenic signals in primary cells result in oncogene-induced senescence (OIS), crucial for protection against cancer development. It has been described in premalignant lesions that OIS requires DNA damage response (DDR) activation, safeguard of the integrity of the genome. Here we demonstrate how the cellular mechanisms involved in oncogenic transformation in a model of glioma uncouple OIS and DDR. We use this tumor type as a paradigm of oncogenic transformation. In human gliomas most of the genetic alterations that have been previously identified result in abnormal activation of cell growth signaling pathways and deregulation of cell cycle, features recapitulated in our model by oncogenic Ras expression and retinoblastoma (Rb) inactivation respectively. In this scenario, the absence of pRb confers a proliferative advantage and activates DDR to a greater extent in a DNA lesion-independent fashion than cells that express only HRasV12. Moreover, Rb loss inactivates the stress kinase DDR-associated p38MAPK by specific Wip1-dependent dephosphorylation. Thus, Rb loss acts as a switch mediating the transition between premalignant lesions and cancer through DDR modulation. These findings may have important implications for the understanding the biology of gliomas and anticipate a new target, Wip1 phosphatase, for novel therapeutic strategies

    Historical influence on the practice of chiropractic radiology: Part I - a survey of Diplomates of the American Chiropractic College of Radiology

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    Background It is known that not all chiropractors follow mainstream guidelines on the use of diagnostic ionising radiation. Various reasons have been discussed in the literature, including using radiography to screen for congenital anomalies, to perform postural analysis, to search for contraindications to spinal manipulation, and to document chiropractic subluxations, i.e., tiny anatomical displacements of vertebrae thought to affect nerves and health. The visualisation of subluxations was the reason chiropractic first adopted the x-ray in 1910. There has never been a study of the influence of this historical paradigm of radiography on the practices of chiropractic radiologists (DACBRs or Diplomates of the American Chiropractic College of Radiology). Methods A survey was administered with a modified Dillman method using SurveyMonkey and supplemented by hard copies distributed at a professional conference. The target population was all active DACBRs. There were 34 items, which consisted of multiple choice and open-ended interrogatives on all three areas in which chiropractic radiologists work: education, clinical practice, and radiology practice. Results The response rate was 38% (73 of 190 DACBRs). Respondents reported that the historical paradigm of radiography was found in all areas of practice, but not as a major aspect. The majority of respondents did not condone that historical paradigm, but many tolerated it, particularly from referring chiropractors. Radiographic subluxation analysis was reportedly perpetuated by private clinical practitioners as well as technique instructors and supervising clinicians in the teaching institutions. Conclusions Within the chiropractic profession, there is a continuing belief in radiographically visible subluxations as a cause of suboptimal health. This situation is sustained in part due to the reticence of other chiropractors to report these practices to licensing and registration boards. Investigation into other structures supporting a vitalistic belief system over science in chiropractic is recommended. In addition, it may be useful to explore remunerative systems that move beyond the inherently conflicted fee-for-service model

    How does study quality affect the results of a diagnostic meta-analysis?

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    Background: The use of systematic literature review to inform evidence based practice in diagnostics is rapidly expanding. Although the primary diagnostic literature is extensive, studies are often of low methodological quality or poorly reported. There has been no rigorously evaluated, evidence based tool to assess the methodological quality of diagnostic studies. The primary objective of this study was to determine the extent to which variations in the quality of primary studies impact the results of a diagnostic meta-analysis and whether this differs with diagnostic test type. A secondary objective was to contribute to the evaluation of QUADAS, an evidence-based tool for the assessment of quality in diagnostic accuracy studies. Methods: This study was conducted as part of large systematic review of tests used in the diagnosis and further investigation of urinary tract infection (UTI) in children. All studies included in this review were assessed using QUADAS, an evidence-based tool for the assessment of quality in systematic reviews of diagnostic accuracy studies. The impact of individual components of QUADAS on a summary measure of diagnostic accuracy was investigated using regression analysis. The review divided the diagnosis and further investigation of UTI into the following three clinical stages: diagnosis of UTI, localisation of infection, and further investigation of the UTI. Each stage used different types of diagnostic test, which were considered to involve different quality concerns. Results: Many of the studies included in our review were poorly reported. The proportion of QUADAS items fulfilled was similar for studies in different sections of the review. However, as might be expected, the individual items fulfilled differed between the three clinical stages. Regression analysis found that different items showed a strong association with test performance for the different tests evaluated. These differences were observed both within and between the three clinical stages assessed by the review. The results of regression analyses were also affected by whether or not a weighting (by sample size) was applied. Our analysis was severely limited by the completeness of reporting and the differences between the index tests evaluated and the reference standards used to confirm diagnoses in the primary studies. Few tests were evaluated by sufficient studies to allow meaningful use of meta-analytic pooling and investigation of heterogeneity. This meant that further analysis to investigate heterogeneity could only be undertaken using a subset of studies, and that the findings are open to various interpretations. Conclusion: Further work is needed to investigate the influence of methodological quality on the results of diagnostic meta-analyses. Large data sets of well-reported primary studies are needed to address this question. Without significant improvements in the completeness of reporting of primary studies, progress in this area will be limited
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