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The use of preoperative radiotherapy in the management of patients with clinically resectable rectal cancer: a practice guideline.

BACKGROUND: This systematic review with meta-analysis was designed to evaluate the literature and to develop recommendations regarding the use of preoperative radiotherapy in the management of patients with resectable rectal cancer. METHODS: The MEDLINE, CANCERLIT and Cochrane Library databases, and abstracts published in the annual proceedings of the American Society of Clinical Oncology and the American Society for Therapeutic Radiology and Oncology were systematically searched for evidence. Relevant reports were reviewed by four members of the Gastrointestinal Cancer Disease Site Group and the references from these reports were searched for additional trials. External review by Ontario practitioners was obtained through a mailed survey. Final approval of the practice guideline report was obtained from the Practice Guidelines Coordinating Committee. RESULTS: Two meta-analyses of preoperative radiotherapy versus surgery alone, nineteen trials that compared preoperative radiotherapy plus surgery to surgery alone, and five trials that compared preoperative radiotherapy to alternative treatments were obtained. Randomized trials demonstrate that preoperative radiotherapy followed by surgery is significantly more effective than surgery alone in preventing local recurrence in patients with resectable rectal cancer and it may also improve survival. A single trial, using surgery with total mesorectal excision, has shown similar benefits in local recurrence. CONCLUSION: For adult patients with clinically resectable rectal cancer we conclude that: Preoperative radiotherapy is an acceptable alternative to the previous practice of postoperative radiotherapy for patients with stage II and III resectable rectal cancer. Both preoperative and postoperative radiotherapy decrease local recurrence but neither improves survival as much as postoperative radiotherapy combined with chemotherapy. Therefore, if preoperative radiotherapy is used, chemotherapy should be added postoperatively to at least patients with stage III disease.

Adult↗

Detecting and managing elder abuse: challenges in primary care. The Research Subcommittee of the Elder Abuse and Self-Neglect Task Force of Hamilton-Wentworth.

OBJECTIVE: To determine family physicians' perceptions of barriers and strategies in the effective detection and appropriate management of abused elderly people. DESIGN: Questionnaire survey; the protocol included an advance notification letter and 3 follow-up mailings. SETTING: Regional Municipality of Hamilton-Wentworth, Ont. PARTICIPANTS: All active nonspecialist physicians who reported seeing elderly patients in their practices were eligible for inclusion. Fifty health service organization (HSO) physicians were randomly selected from among those listed with the HSO Mental Health Program, and 200 fee-for-service physicians were randomly selected from the Canadian Medical Directory. Of the 189 eligible physicians 122 returned completed questionnaires, a response rate of 65%. OUTCOME MEASURES: Physicians' ratings of the importance of potential barriers in assisting older people experiencing abuse and of the usefulness of strategies for dealing with elder abuse. RESULTS: Physicians identified the following barriers as fairly or very important: denial of abuse, resistance to intervention, not knowing where to call for help, lack of protocols to assess and respond to abuse, lack of guidelines about confidentiality, fear of reprisal, and lack of knowledge of the prevalence and definition of elder abuse. Strategies deemed to be helpful included a single agency to call, a directory of services, a list of resource people, an educational package, guidelines for detection and management, reimbursement for time spent on legal matters, continuing education, revision of fee structure and a central library of resources on elder abuse. CONCLUSION: Although the physicians perceived numerous barriers to their detection and management of elder abuse, they identified many strategies that could be implemented at a local level. Preparation of an algorithm to help physicians is the next phase of this work.

Aged↗

Diversity and abundance of Crenarchaeota in terrestrial habitats studied by 16S RNA surveys and real time PCR.

Novel phylogenetic lineages of as yet uncultivated crenarchaeota have been frequently detected in low to moderate-temperature, marine and terrestrial environments. In order to gain a more comprehensive view on the distribution and diversity of Crenarchaeota in moderate habitats, we have studied 18 different terrestrial and freshwater samples by 16S rDNA-based phylogenetic surveys. In seven different soil samples of diverse geographic areas in Europe (forest, grassland, ruderal) and Asia (permafrost, ruderal) as well as in two microbial mats, we have consistently found one particular lineage of crenarchaeota. The diversity of Crenarchaeota in freshwater sediments was considerably higher with respresentative 16S rDNA sequences distributed over four different groups within the moderate crenarchaeota. Systematic analysis of a 16S rDNA universal library from a sandy ecosystem containing 800 clones exclusively revealed the presence of the soil-specific crenarchaeotal cluster. With primers specific for non-thermophilic crenarchaeota we established a rapid method to quantify archaeal 16S rDNA in real time PCR. The relative abundance of crenarchaeotal rDNA was 0.5-3% in the bulk soil sample and only 0.16% in the rhizosphere of the sandy ecosystem. A nearby agricultural setting yielded a relative abundance of 0.17% crenarchaeotal rDNA. In total our data suggest that soil crenarchaeota represent a stable and specific component of the microbiota in terrestrial habitats.

Bacteria↗

Teaching information literacy skills: an evaluation.

This paper describes an evaluation of a curriculum-integrated information literacy programme in an undergraduate nursing course. The aim of the programme was to provide students with an awareness of the discipline's literature and the skills to locate and retrieve the literature. A multidimensional process for determining nursing students' development was utilised in the evaluation of the programme. Pre- and post-programme questionnaires were distributed to a cohort of students who undertook the programme. A cohort of more senior students who had not undertaken the information literacy programme was utilised as a comparison group. Questionnaire results were analysed using a range of inferential statistics. This paper will focus on two main findings related to objective measures of information literacy skills. These include pre-programme/post-programme change in student performance and differences in student performance between those who undertook the programme and those who did not. The programme demonstrated its effectiveness in developing information literacy skills, however the challenge remains for both academics and students to ensure that these skills are consolidated and extended for effective life-long learning.

Catalogs, Library↗

A review of US anthropometric reference data (1971-2000) with comparisons to both stylized and tomographic anatomic models.

Two classes of anatomic models currently exist for use in both radiation protection and radiation dose reconstruction: stylized mathematical models and tomographic voxel models. The former utilize 3D surface equations to represent internal organ structure and external body shape, while the latter are based on segmented CT or MR images of a single individual. While tomographic models are clearly more anthropomorphic than stylized models, a given model's characterization as being anthropometric is dependent upon the reference human to which the model is compared. In the present study, data on total body mass, standing/sitting heights and body mass index are collected and reviewed for the US population covering the time interval from 1971 to 2000. These same anthropometric parameters are then assembled for the ORNL series of stylized models, the GSF series of tomographic models (Golem, Helga, Donna, etc), the adult male Zubal tomographic model and the UF newborn tomographic model. The stylized ORNL models of the adult male and female are found to be fairly representative of present-day average US males and females, respectively, in terms of both standing and sitting heights for ages between 20 and 60-80 years. While the ORNL adult male model provides a reasonably close match to the total body mass of the average US 21-year-old male (within approximately 5%), present-day 40-year-old males have an average total body mass that is approximately 16% higher. For radiation protection purposes, the use of the larger 73.7 kg adult ORNL stylized hermaphrodite model provides a much closer representation of average present-day US females at ages ranging from 20 to 70 years. In terms of the adult tomographic models from the GSF series, only Donna (40-year-old F) closely matches her age-matched US counterpart in terms of average body mass. Regarding standing heights, the better matches to US age-correlated averages belong to Irene (32-year-old F) for the females and Golem (38-year-old M) for the males. Both Helga (27-year-old F) and Donna, however, provide good matches to average US sitting heights for adult females, while Golem and Otoko (male of unknown age) yield sitting heights that are slightly below US adult male averages. Finally, Helga is seen as the only GSF tomographic female model that yields a body mass index in line with her average US female counterpart at age 26. In terms of dose reconstruction activities, however, all current tomographic voxel models are valuable assets in attempting to cover the broad distribution of individual anthropometric parameters representative of the current US population. It is highly recommended that similar attempts to create a broad library of tomographic models be initiated in the United States and elsewhere to complement and extend the limited number of tomographic models presently available for these efforts.

Adult↗

[The students' page. Are we making good use of this space?].

The current study aimed to make a survey of the articles written by nursing students that were published through the Students' Pages in the Brazilian Nursing Journal, Nursing Journal from Bahia and Nursing Journal from São Paulo from 1982 to 1995, in order to verify if this space is being used and the themes that have been approached. This investigation evidenced that, from the three studied periodicals, 109 issues were available in the library, 15 presented articles published in the Students' Pages and 21 texts were found. Among these, the most approached themes are related to nursing practice.

Brazil↗

The use and selection of sources in information seeking: the Cancer Information Service experience. Part 8.

The Cancer Information Service (CIS), the voice of the National Cancer Institute (NCI) for more than 20 years, disseminates information through two channels: a toll-free telephone service (1-800-4-CANCER) and an outreach program which develops partnerships with organizations that reach underserved populations. In 1996, the telephone service handled approximately 500,000 calls on a range of topics, including cancer treatment, clinical trials, coping issues, referrals to services, prevention, causes, and symptoms of cancer. As part of a national telephone service user survey, conducted in 1996, that examined the impact of the CIS program, callers were asked what additional sources they went to for the same information that they requested from the CIS. The survey revealed that the CIS plays a critical role for information seekers. Almost 59% of surveyed callers contacted no other sources to address the topic they discussed with the CIS. Almost half of the callers who contacted other sources made all of those contacts before calling the CIS. Younger callers (under 40), those with a higher level of education, and those seeking information about treatment and causes of cancer were more likely to contact other sources for the same information. Health professionals, libraries, and bookstores were the most commonly used non-CIS sources. This variety in information seeking highlights the need for services, like the CIS, that can meet the diverse information needs of callers.

Adolescent↗

Audiovisual materials: a survey of bibliographic controls in distributors' catalogs.

The current pattern of bibliographic control in audio-visual distributors' catalogs is described. Eight bibliographic control elements are defined, and the criteria for evaluating the occurrence of these elements in sixty-four sample catalogs are specified. When the distributors are grouped according to category, such as educational or commercial, the pattern of bibliographic control has three distinct clusters of elements. When the distributors are grouped by the number of titles handled, there is no clear pattern. The implications of these patterns are discussed in terms of practical library reference services. A solution to the problem of bibliographic control of health science audiovisual materials is proposed.

Audiovisual Aids↗

MEDLINE services to the developing countries.

Supplying MEDLINE services to a widely dispersed user population in the developing countries creates numerous problems not encountered by other MEDLINE centres. The inability to interact with the user complicates system promotion and makes search formulation sometimes a gamble. Nevertheless, an evaluation survey has shown high user satisfaction. Of great concern is the still inadequate solution of document delivery. Near-term objectives are the broadening of geographic coverage and the integration of search processing with supporting hard copy supply.

Developing Countries↗

Expression profiling of favorable and unfavorable neuroblastomas.

Neuroblastomas show remarkable biological heterogeneity, resulting in favorable or unfavorable outcomes. To survey the differences in gene expression profiles between favorable and unfavorable neuroblastomas, we analyzed ten favorable neuroblastoma samples from patients whose tumors consequently regressed or matured and ten unfavorable tumor samples from patients who consequently died of disease using the microarray technique. In each sample, total RNA was labeled with Cy3 or Cy5 in reverse-trancriptase reaction and hybridized with our original microarray prepared with a cDNA library of human fetal brain. Microarray analysis revealed that 43 genes, including MYCN, hTERT, NME1 and cell cycle regulatory protein-coding genes, were highly expressed in unfavorable neuroblastomas, while another 80 genes were detected as highly expressed in favorable tumors, including neuronal differentiating genes and apoptotic inducing genes. Among favorable neuroblastoma samples, highly expressing genes in regressing tumors were different from those in maturing tumors. Expression profiling data revealed the existence of up-regulated and down-regulated gene clusters in favorable and unfavorable tumors. This cluster analysis is a powerful procedure to distinguish unfavorable tumors from favorable tumors as well as regressing tumors from maturing tumors among favorable tumors. The information obtained from expression profiling would clarify the key genes for cell growth, regression or maturation of neuroblastoma cells, and these genes will become diagnostic and therapeutic targets in human neuroblastoma in the future.

Apoptosis↗

Getting nutrition education into medical schools: a computer-based approach.

Despite awareness of the importance of nutrition as part of medical student's education, numerous barriers exist to incorporating nutrition education into the medical school curriculum. Chief among such barriers is that most medical schools do not have faculty trained specifically in nutrition. A curriculum is needed that can deliver comprehensive nutrition information that is consistent across medical schools. One way to deliver this information is to use computer-assisted instruction (CAI). To meet the different needs of medical schools and provide a consistent base of nutrition information, we developed a series of interactive, multimedia educational programs (Nutrition in Medicine) that teach the basic principles of nutritional science and apply those principles in a case-oriented approach. Curriculum content is derived from the American Society for Clinical Nutrition consensus guidelines. These modules offer the advantages of accessibility, self-paced study, interactivity, immediate feedback, and tracking of student performance. Modules are distributed free to all US medical schools. Preliminary data from surveys gathered by our team at the University of North Carolina at Chapel Hill indicate that 73 US medical schools use, or are planning to use, these modules; more schools are currently evaluating the programs. Successful implementation of CAI requires easy program access, faculty training, adequate technical support, and faculty commitment to the programs as a valuable resource. CAI fails when the program is just placed in the library and students are told to use it when they can find the time.

Computer-Assisted Instruction↗

Expression of the tumor-associated gene MN: a potential biomarker for human renal cell carcinoma.

MN is a novel cell surface antigen originally detected in human HeLa cells. Although it is also expressed in normal gastric mucosa, this antigen was previously found to be expressed in cells with a malignant phenotype in certain tissues of the female genital tract (cervix and ovary). Using an oligonucleotide primer set specific for MN-complimentary DNA, we performed reverse transcription-PCR assays on RNAs extracted from human cell lines and tissues to evaluate whether this marker might be expressed at other sites. RNA libraries extracted from normal human heart, lung, kidney, prostate, peripheral blood, brain, placenta, and muscle were negative for MN expression. RNAs extracted from liver and pancreatic tissue were positive for MN expression. Three of six renal cancer cell lines tested revealed MN expression. In addition, 12 of 17 samples of human renal cell carcinoma tissue tested positive for MN, all 12 of which were clear cell adenocarcinomas. This survey identified a unique association of MN expression with renal cell cancers, especially those of the clear cell variety, suggesting that MN is a potential marker for the diagnosis, staging, and therapeutic monitoring of renal cell carcinoma in humans.

Antigens, Neoplasm↗

Analysis and prediction of functionally important sites in proteins.

The rapidly increasing volume of sequence and structure information available for proteins poses the daunting task of determining their functional importance. Computational methods can prove to be very useful in understanding and characterizing the biochemical and evolutionary information contained in this wealth of data, particularly at functionally important sites. Therefore, we perform a detailed survey of compositional and evolutionary constraints at the molecular and biological function level for a large set of known functionally important sites extracted from a wide range of protein families. We compare the degree of conservation across different functional categories and provide detailed statistical insight to decipher the varying evolutionary constraints at functionally important sites. The compositional and evolutionary information at functionally important sites has been compiled into a library of functional templates. We developed a module that predicts functionally important columns (FIC) of an alignment based on the detection of a significant "template match score" to a library template. Our template match score measures an alignment column's similarity to a library template and combines a term explicitly representing a column's residue composition with various evolutionary conservation scores (information content and position-specific scoring matrix-derived statistics). Our benchmarking studies show good sensitivity/specificity for the prediction of functional sites and high accuracy in attributing correct molecular function type to the predicted sites. This prediction method is based on information derived from homologous sequences and no structural information is required. Therefore, this method could be extremely useful for large-scale functional annotation.

Binding Sites↗

Hospital doctors' self-rated skills in and use of evidence-based medicine - a questionnaire survey.

RATIONALE, AIMS AND OBJECTIVES: Problems in understanding basic aspects of evidence-based medicine (EBM) may form barriers to its implementation into clinical practice. We examined hospital doctors' skills in EBM terms and related these skills to their use of information sources, critical appraisal, and implementation of EBM into clinical practice. METHODS: A self-administered questionnaire was sent to all hospital doctors (n = 376) at a university hospital in Denmark, including 12 questions on methodological terms frequently used in evidence-based literature plus one non-existing dummy term. Furthermore, participants were asked about their use of various information sources, self-rated skills of critical appraisal of standard scientific literature, and level of implementation of evidence-based principles in daily clinical settings. Based on the answers to the 12 evidence-based methodological terms, we calculated a familiarity score. RESULTS: Proportion of responding was 60% (n = 225), but representative for all hospital doctors regarding background data. Ten doctors (4.4%) could define and explain all 12 methodological terms. The majority of all doctors showed interest in knowing more about the terms. Fifty-six per cent knew the dummy term. Doctors mainly consulted traditional and possibly insufficient sources (textbooks, colleagues, scientific journals) when searching for clinical evidence. The Cochrane Library was the least consulted information source and had never been consulted by 49%. Only 18% always practised EBM. More reliance on PubMed and The Cochrane Library as information sources, more competence of critical appraisal, and more frequent practise of EBM were significantly (P < 0.001) associated with a higher familiarity score. Compared to seldom or never users of The Cochrane Library, frequent users had significantly higher academic degree (P = 0.01), familiarity score (P < 0.001), and use of PubMed (P = 0.0004). DISCUSSION AND CONCLUSIONS: Most hospital doctors seem to lack knowledge of key methodological evidence-based medicine terms. This may form a barrier when consulting EBM sources and to the implementation of EBM into clinical practice.

Adult↗

Profiling patterned transcripts in Drosophila embryos.

Here we describe a high-throughput screen to isolate transcripts with spatially restricted patterns of expression in early embryos. Our approach utilizes robotic automation for rapid analysis of sequence-selected cDNAs in a whole-mount in situ hybridization assay. We determined the spatial distribution of a random collection of 778 different genes from an embryonic cDNA library and show that a significant fraction of these exhibit patterned profiles of expression. In addition, gene ontology studies revealed groups of gene products exhibiting shared expression patterns, providing new insights into the largely overlooked effector molecules that function in development. As described in this paper, automated hybridization to whole-mount embryos in situ proved to be straightforward and provided us with a very powerful method for the global survey of gene expression in early embryos. From the perspective of biological significance, our finding that many spatially restricted transcripts correspond to loci encoding novel transcripts that have not been previously identified in nearly saturating genetic screens for maternal effect and zygotic lethals is particularly notable.

Animals↗

Digital transcriptome analysis indicates adaptive mechanisms in the heart of a hibernating mammal.

Survival of near-freezing body temperatures and reduced blood flow during hibernation is likely the result of changes in the expression of specific genes. In this study, we described a comprehensive survey of mRNAs in the heart of the thirteen-lined ground squirrel (Spermophilus tridecemlineatus) before and during hibernation. The heart was chosen for this study because it is a contractile organ that must continue to work despite body temperatures of 5 degrees C and the lack of food for periods of 5-6 mo. We used a digital gene expression assay involving high-throughput sequencing of directional cDNA libraries from hearts of active and hibernating ground squirrels to determine the identity and frequency of 3,532 expressed sequence tags (ESTs). Statistical analysis of the active and hibernating heart expression profile indicated the differential regulation of 48 genes based on a P < or = 0.03 threshold. Several of the differentially expressed genes identified in this screen encode proteins that likely account for uninterrupted cardiac function during hibernation, including those involved in metabolism, contractility, Ca2+ handling, and low-temperature catalysis. A sampling of genes showing higher expression during hibernation includes phosphofructokinase, pancreatic triacylglycerol lipase, pyruvate dehydrogenase kinase 4 (PDK4), aldolase A, sarco(endo)plasmic reticulum Ca2+-ATPase 2a (SERCA2a), titin, and four-and-a-half LIM domains protein 2 (FHL2). Genes showing reduced levels of expression during hibernation include cyclin-dependent kinase 2-associated protein 1 (CDK2AP1), troponin C, phospholamban, Ca2+/calmodulin-dependent protein kinase II (CaMKII), calmodulin, and four subunits of cytochrome c oxidase.

Adaptation, Physiological↗

Follow-up of patients with curatively resected colorectal cancer: a practice guideline.

BACKGROUND: A systematic review was conducted to evaluate the literature regarding the impact of follow-up on colorectal cancer patient survival and, in a second phase, recommendations were developed. METHODS: The MEDLINE, CANCERLIT, and Cochrane Library databases, and abstracts published in the 1997 to 2002 proceedings of the annual meeting of the American Society of Clinical Oncology were systematically searched for evidence. Study selection was limited to randomized trials and meta-analyses that examined different programs of follow-up after curative resection of colorectal cancer where five-year overall survival was reported. External review by Ontario practitioners was obtained through a mailed survey. Final approval of the practice guideline report was obtained from the Practice Guidelines Coordinating Committee. RESULTS: Six randomized trials and two published meta-analyses of follow-up were obtained. Of six randomized trials comparing one follow-up program to a more intense program, only two individual trials detected a statistically significant survival benefit favouring the more intense follow-up program. Pooling of all six randomized trials demonstrated a significant improvement in survival favouring more intense follow-up (Relative Risk Ratio 0.80 (95%CI, 0.70 to 0.91; p = 0.0008). Although the rate of recurrence was similar in both of the follow-up groups compared, asymptomatic recurrences and re-operations for cure of recurrences were more common in patients with more intensive follow-up. Trials including CEA monitoring and liver imaging also had significant results, whereas trials not including these tests did not. CONCLUSION: Follow-up programs for patients with curatively resected colorectal cancer do improve survival. These follow-up programs include frequent visits and performance of blood CEA, chest x-rays, liver imaging and colonoscopy, however, it is not clear which tests or frequency of visits is optimal. There is a suggestion that improved survival is due to diagnosis of recurrence at an earlier, asymptomatic stage which allows for more curative resection of recurrence. Based on this evidence and consideration of the biology of colorectal cancer and present practices, a guideline was developed. Patients should be made aware of the risk of disease recurrence or second bowel cancer, the potential benefits of follow-up and the uncertainties requiring further clinical trials. For patients at high-risk of recurrence (stages IIb and III) clinical assessment is recommended when symptoms occur or at least every 6 months the first 3 years and yearly for at least 5 years. At the time of those visits, patients may have blood CEA, chest x-ray and liver imaging. For patients at lower risk of recurrence (stages I and Ia) or those with co-morbidities impairing future surgery, only visits yearly or when symptoms occur. All patients should have a colonoscopy before or within 6 months of initial surgery, and repeated yearly if villous or tubular adenomas >1 cm are found; otherwise repeat every 3 to 5 years. All patients having recurrences should be assessed by a multidisciplinary team in a cancer centre.

Adult↗

Chasing the ambulance. The emerging crisis in the preservation of modern health records.

In this brief essay we argue that the best efforts of archivists, scholars, and practitioners within the National Health Service have not prevented the wholesale destruction of the bulk of patient records created during the twentieth century. This is a matter of vital concern not merely for historians of modern medicine. Important clinical work has frequently been undertaken on materials which have survived, usually by chance or by the foresight of physicians, matrons, and administrators. Even the significant fragments of historical documents which remain in the hands of the health authorities have been threatened by the continuing drive to reduce storage and maintenance costs within hospitals. Archivists and academics have struggled to address the problems of sampling, storage, and access which the enormous bulk of modern records present. In this essay we suggest that the first step must be to raise awareness amongst professionals and the public of the extent to which any future history of the medical services and of patient care will depend on a reasonable rate of survival of these records. The second step must be to confront the problem of resources and the inevitable task of selection which must form the foundations of any long-term policy of preservation. An initial survey of archival materials in Devon indicates that the records of community health care form a substantial and potentially invaluable research source for future historians, though their relevance has rarely been recognized within the academic community.

Archives↗