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Natural language processing and visualization in the molecular imaging domain.

Molecular imaging is at the crossroads of genomic sciences and medical imaging. Information within the molecular imaging literature could be used to link to genomic and imaging information resources and to organize and index images in a way that is potentially useful to researchers. A number of natural language processing (NLP) systems are available to automatically extract information from genomic literature. One existing NLP system, known as BioMedLEE, automatically extracts biological information consisting of biomolecular substances and phenotypic data. This paper focuses on the adaptation, evaluation, and application of BioMedLEE to the molecular imaging domain. In order to adapt BioMedLEE for this domain, we extend an existing molecular imaging terminology and incorporate it into BioMedLEE. BioMedLEE's performance is assessed with a formal evaluation study. The system's performance, measured as recall and precision, is 0.74 (95% CI: [.70-.76]) and 0.70 (95% CI [.63-.76]), respectively. We adapt a JAVA viewer known as PGviewer for the simultaneous visualization of images with NLP extracted information.

Animals↗

Continuing controversy over monitoring men with localized prostate cancer: a systematic review of programs in the prostate specific antigen era.

PURPOSE: There is continuing controversy over the most appropriate treatment for screen detected and clinically localized prostate cancer, and increasing interest in monitoring such men initially with radical treatment targeted at cancers showing signs of progressive potential but while they are still curable. Current evidence on monitoring protocols and biomarkers used to predict disease progression was systematically reviewed. MATERIALS AND METHODS: The MEDLINE and Excerpta Medica (EMBASE) bibliographic databases were searched from 1988 to October 2004, supplemented by manual searches of reference lists, focusing on studies reporting monitoring of men with localized prostate cancer. RESULTS: A total of 48 potentially eligible articles were found but only 5 studies, in which there was a total of 451 participants, restricted entry criteria to men with clinically localized (T1-T2) prostate cancer. Monitoring protocols varied with little consensus, although the majority used prostate specific antigen and digital rectal examination, while some added re-biopsy to assess progression. Actuarial probabilities of freedom from disease progression at 4 to 5 years of followup were 67% to 72%. However, up to 50% of men abandoned monitoring within 2 years, largely because of anxiety related to increasing prostate specific antigen rather than objective evidence of disease progression. There was no robust evidence to support prostate specific antigen doubling times or velocity to identify men in whom disease may progress. Studies were characterized by small sample size, short-term followup, observer bias and uncertain validity around variable definitions of progression. CONCLUSIONS: Current evidence suggests that some form of monitoring would be a suitable treatment option in men with localized prostate cancer but there is little consensus over what markers should be used in such a program or how progression should be properly defined. The search for a method that safely identifies men with prostate cancer who could avoid radical intervention must continue.

Disease Progression↗

Does enteral nutrition compared to parenteral nutrition result in better outcomes in critically ill adult patients? A systematic review of the literature.

OBJECTIVE: Nutritional support is part of the standard of care for the critically ill adult patient. In the average patient in the intensive care unit who has no contraindications to enteral nutrition (EN) or parenteral nutrition (PN), the choice of route for nutritional support may be influenced by several factors. Because EN and PN are associated with risks and benefits, we systematically reviewed and critically appraised the literature to compare EN with PN the critically ill patient. METHODS: We searched computerized bibliographic databases, personal files, and relevant reference lists to identify potentially eligible studies. Only randomized clinical trials that compared EN with PN in critically ill patients with respect to clinically important outcomes were included in this review. In an independent fashion, relevant data on the methodology and outcomes of primary studies were abstracted in duplicate. The studies were subsequently aggregated statistically. RESULTS: There were 13 studies that met the inclusion criteria and, hence, were included in our meta-analysis. The use of EN as opposed to PN was associated with a significant decrease in infectious complications (relative risk = 0.64, 95% confidence interval = 0.47 to 0.87, P = 0.004) but not with any difference in mortality rate (relative risk = 1.08, 95% confidence interval = 0.70 to 1.65, P = 0.7). There was no difference in the number of days on a ventilator or length of stay in the hospital between groups receiving EN or PN (Standardized Mean Difference [SMD] = 0.07, 95% confidence interval = -0.2 to 0.33, P = 0.6). PN was associated with a higher incidence of hyperglycemia. Data that compared days on a ventilator and the development of diarrhea in patients who received EN versus PN were inconclusive. In the EN and PN groups, complications with enteral and parenteral access were seen. Four studies documented cost savings with EN as opposed to PN. CONCLUSION: The use of EN as opposed to PN results in an important decrease in the incidence of infectious complications in the critically ill and may be less costly. EN should be the first choice for nutritional support in the critically ill.

Costs and Cost Analysis↗

Foreign direct investment and trade in health services: a review of the literature.

Globalization is a key challenge facing health policy-makers. A significant aspect of this is direct trade in health services, a result of the rise of transnational corporations, challenges in health care financing, porous borders and improved technology creating the scope for increased 'foreign direct investment' (FDI) in health care. This has gathered momentum with the General Agreement on Trade in Services (GATS), which aims to further liberalize trade in services, and within which FDI has been noted as perhaps the most critical area for trade negotiation. Given the rapid development of this area, there are little empirical data. This paper therefore seeks to provide the first comprehensive and systematic review of evidence concerning FDI and health services. This process included electronic bibliographic database searches, website searches and correspondence with experts in the area of trade in health services, from which 76 papers, books and reports were reviewed. Perhaps due to the rapid developments in this area, most of the literature is speculative, polarized between those arguing for the benefits of liberalization and those arguing against. However, there seem to be three issues which emerge as of most importance: (i) the extent to which a national health system is commercialized per se is of more significance than whether investment in it is foreign or domestic; (ii) the national regulatory environment and its 'strength' will significantly determine the economic and health impact of FDI, the effectiveness of safeguard measures, and the stability of GATS commitments; and (iii) any negotiations will depend upon parties having a common understanding of what is being negotiated, and the interpretation of key definitions is thus critical. Each of these issues is explored in some depth, with the overall conclusion that countries should take a step back and first think through the risks and benefits of commercialization of their health sector, rather than being sidetracked in to considering the level of foreign investment.

Commerce↗

Maternity referral systems in developing countries: current knowledge and future research needs.

A functioning referral system is generally considered to be a necessary element of successful Safe Motherhood programmes. This paper draws on a scoping review of available literature to identify key requisites for successful maternity referral systems in developing countries, to highlight knowledge gaps, and to suggest items for a future research agenda. Key online social science, medical and health system bibliographic databases, and websites were searched in July 2004 for evidence relating to referral systems for maternity care. Documentary evidence on implementation is scarce, but it suggests that many healthcare systems in developing countries are failing to optimise women's rapid access to emergency obstetric care, and that the poor and marginalised are affected disproportionately. Likely requisites for successful maternity referral systems include: a referral strategy informed by the assessment of population needs and health system capabilities; an adequately resourced referral centre; active collaboration between referral levels and across sectors; formalised communication and transport arrangements; agreed setting-specific protocols for referrer and receiver; supervision and accountability for providers' performance; affordable service costs; the capacity to monitor effectiveness; and underpinning all of these, policy support. Theoretically informed social and organisational research is required on the referral care needs of the poor and marginalised, on the maternity workforce and organisation, and on the implications of the mixed economy of healthcare for referral networks. Clinical research is required to determine how maternity referral fits within newborn health priorities and where the needs are different. Finally, research is required to determine how and whether a more integrated approach to emergency care systems may benefit women and their communities.

Developing Countries↗

Cancer information resources: digital and online sources.

The Internet is becoming an increasingly important source of information on cancer. This article highlights major sites of credible information on cancer and describes the types of information each of these sites contains. Large directories that help point the visitor to additional cancer-related sites are described, as are searchable databases of information on cancer as a disease, its diagnosis, and treatment. Sources of information on chemical carcinogens, mechanistic studies, and applied cancer toxicology are also described. These Internet sources of cancer information address the needs of toxicologists, environmental and occupational health scientists, cancer researchers and clinicians, government regulators, the public, and cancer survivors and their caregivers.

Animals↗

A meta-analysis of alcohol consumption and the risk of 15 diseases.

BACKGROUND: To compare the strength of evidence provided by the epidemiological literature on the association between alcohol consumption and the risk of 14 major alcohol-related neoplasms and non-neoplastic diseases, plus injuries. METHODS: A search of the epidemiological literature from 1966 to 1998 was performed by several bibliographic databases. Meta-regression models were fitted considering fixed and random effect models and linear and nonlinear effects of alcohol intake. The effects of some characteristics of the studies, including an index of their quality, were considered. RESULTS: Of the 561 initially reviewed studies, 156 were selected for meta-analysis because of their a priori defined higher quality, including a total of 116,702 subjects. Strong trends in risk were observed for cancers of the oral cavity, esophagus and larynx, hypertension, liver cirrhosis, chronic pancreatitis, and injuries and violence. Less strong direct relations were observed for cancers of the colon, rectum, liver, and breast. For all these conditions, significant increased risks were also found for ethanol intake of 25 g per day. Threshold values were observed for ischemic and hemorrhagic strokes. For coronary heart disease, a J-shaped relation was observed with a minimum relative risk of 0.80 at 20 g/day, a significant protective effect up to 72 g/day, and a significant increased risk at 89 g/day. No clear relation was observed for gastroduodenal ulcer. CONCLUSIONS: This meta-analysis shows no evidence of a threshold effect for both neoplasms and several non-neoplastic diseases. J-shaped relations were observed only for coronary heart disease.

Alcohol Drinking↗

The effectiveness of endoscopy in the management of dyspepsia: a qualitative systematic review.

PURPOSE: Dyspepsia is a common primary care condition, yet its optimal management is poorly defined. We reviewed the literature to answer the following questions about patients with dyspepsia: 1) Does endoscopy result in improved patient outcomes? 2) Does endoscopy result in a reduction in the use of subsequent medical resources? 3) Does endoscopy result in improved medical decision making? 4) Is endoscopy cost effective? METHODS: We performed a systematic review of English-language articles in the MEDLINE, HEALTHSTAR, and EMBASE computerized bibliographic databases from January 1985 to July 1998. We included all studies, including decision analyses, with information about the effectiveness of endoscopy, as measured by its impact on patient outcomes, resource utilization, clinical decision making, or cost effectiveness. Two independent reviewers abstracted data from each study, and assessed its methodologic quality. RESULTS: Twenty-one studies met the inclusion criteria. For 3 of the 4 clinical questions, the weight of evidence does not support the effectiveness of endoscopy. The largest randomized clinical trial comparing endoscopy with empiric therapy demonstrates equivalent symptoms and quality of life at 1 year, with increased patient satisfaction and lower costs for initial endoscopy. Suboptimal study design, including lack of appropriate comparison groups, limit studies measuring the impact of endoscopy on resource utilization and decision-making. Decision analyses indicate that noninvasive H pylori testing followed by anti-H pylori therapy or empiric antisecretory therapy is more cost effective than initial endoscopy. CONCLUSIONS: With the exception of one randomized clinical trial, the preponderance of available data does not support the effectiveness of endoscopy in the management of dyspepsia. Prospective clinical trials that evaluate patient outcomes and resource utilization, and take H pylori status into account, are needed to determine the effectiveness of endoscopy in the management of dyspepsia.

Anxiety↗

[Intracoronary brachytherapy: a meta-analysis].

Intracoronary brachytherapy aims at a reduction of in-stent restenosis by lessening neo-intimal proliferation. To assess its clinical potential, a systematic review of the literature indexed in the standard biomedical bibliographic databases selected eight prospective randomized clinical trials; seven of them, comparing coronary brachytherapy and non-treatment or placebo, have been included in the present meta-analysis. This analysis confirms the angiographic benefit of this procedure, as reported in the individual studies; it also shows, however an excess of clinical adverse effects not exhibited by any individual trial. Therefore, intracoronary brachytherapy cannot be recommended as routine practice, while one cannot rule out its interest in special situations.

Angioplasty, Balloon, Coronary↗

Albumin versus hydroxyethyl starch in cardiopulmonary bypass surgery: a meta-analysis of postoperative bleeding.

BACKGROUND: This meta-analysis tested the hypothesis that cumulative blood loss during the first 24 hours after cardiopulmonary bypass is lower in patients exposed to albumin than hydroxyethyl starch (HES). METHODS: Randomized controlled trials comparing albumin and HES in cardiopulmonary bypass patients were identified by bibliographic database searches and other methods. RESULTS: Sixteen trials involving 653 randomized patients were included. In 88% of randomized comparisons, postoperative bleeding was lower in the albumin group, and the standardized mean difference in bleeding favoring albumin across all trials (-0.24; 95% confidence interval, -0.40 to -0.08) was statistically significant. Bleeding differences between albumin and either high or medium molecular weight HES were similar. In trials of adults, the pooled mean blood loss in the albumin group was 693+/-350 mL compared with 789+/-487 mL in the HES group. The estimated proportion of adult albumin group patients with blood loss of more than 1,000 mL was 19% compared with 33% of adult HES group patients. Conclusions. Postoperative blood loss is significantly lower in cardiopulmonary bypass patients exposed to albumin than HES.

Aged↗

Understanding prognosis to improve rehabilitation: the example of lateral elbow pain.

OBJECTIVE: A systematic overview of evidence aimed at determining the clinical course of lateral elbow pain and prognostic factors that affect elbow pain duration and outcomes. DATA SOURCES: Online bibliographic database searches from 1983 to 1994; information requests from selected authors and bibliography screenings. STUDY SELECTION: One author reviewed 424 articles; 40 met the following eligibility criteria: any study with primary data on soft tissue injuries specific to the elbow which referred to prognosis or reported use of any outcome measure. DATA ABSTRACTION: Strength of evidence grade based on clinical epidemiological validity assessment. Criteria included in the validity assessment included case definition, patient selection, follow-up, outcome, prognostic factors, and analysis. All eligible studies were independently assessed by two investigators. DATA SYNTHESIS: Four studies (10%) were judged to provide moderate strength of evidence; no studies were graded as providing strong evidence on prognosis. All four moderate-quality studies were clinical trials of short duration. One study indicated that site of lesion and prior occurrence may be predictive of poorer outcome in patients with lateral epicondylitis. CONCLUSION: The majority of studies on lateral elbow pain were limited by methodological weaknesses in selection and definition of the study population, length of follow-up, and analysis of prognostic factors. Estimates of duration were only available from weaker studies with longer follow-up times; significant subject heterogeneity in the weaker studies prevented a determination of usual clinical course. More methodologically rigorous research on prognosis could assist clinicians in patient care and evaluation of interventions.

Arthralgia↗

Effectiveness of exercise therapy: a best-evidence summary of systematic reviews.

The purpose of this project was to summarise the available evidence on the effectiveness of exercise therapy for patients with disorders of the musculoskeletal, nervous, respiratory, and cardiovascular systems. Systematic reviews were identified by means of a comprehensive search strategy in 11 bibliographic databases (08/2002), in combination with reference tracking. Reviews that included (i) at least one randomised controlled trial investigating the effectiveness of exercise therapy, (ii) clinically relevant outcome measures, and (iii) full text written in English, German or Dutch, were selected by two reviewers. Thirteen independent and blinded reviewers participated in the selection, quality assessment and data-extraction of the systematic reviews. Conclusions about the effectiveness of exercise therapy were based on the results presented in reasonable or good quality systematic reviews (quality score > or = 60 out of 100 points). A total of 104 systematic reviews were selected, 45 of which were of reasonable or good quality. Exercise therapy is effective for patients with knee osteoarthritis, sub-acute (6 to 12 weeks) and chronic (> or = 12 weeks) low back pain, cystic fibrosis, chronic obstructive pulmonary disease, and intermittent claudication. Furthermore, there are indications that exercise therapy is effective for patients with ankylosing spondylitis, hip osteoarthritis, Parkinson's disease, and for patients who have suffered a stroke. There is insufficient evidence to support or refute the effectiveness of exercise therapy for patients with neck pain, shoulder pain, repetitive strain injury, rheumatoid arthritis, asthma, and bronchiectasis. Exercise therapy is not effective for patients with acute low back pain. It is concluded that exercise therapy is effective for a wide range of chronic disorders.

Chronic Disease↗

Kinetic parameters of cholinesterase interactions with organophosphates: retrieval and comparison tools available through ESTHER database: ESTerases, alpha/beta Hydrolase Enzymes and Relatives.

Cholinesterases are targets for organophosphorus compounds which are used as insecticides, chemical warfare agents and drugs for the treatment of disease such as glaucoma, or parasitic infections. The widespread use of these chemicals explains the growing of this area of research and the ever increasing number of sequences, structures, or biochemical data available. Future advances will depend upon effective management of existing information as well as upon creation of new knowledge. The ESTHER database goal is to facilitate retrieval and comparison of data about structure and function of proteins presenting the alpha/beta hydrolase fold. Protein engineering and in vitro production of enzymes allow direct comparison of biochemical parameters. Kinetic parameters of enzymatic reactions are now included in the database. These parameters can be searched and compared with a table construction tool. ESTHER can be reached through internet (http://www.ensam.inra.fr/cholinesterase). The full database or the specialised X-window Client-server system can be downloaded from our ftp server (ftp://ftp.toulouse.inra.fr./pub/esther). Forms can be used to send updates or corrections directly from the web.

Animals↗

The future of human ovarian cryopreservation and transplantation: fertility and beyond.

OBJECTIVE: To review the current progress in ovarian cryopreservation and transplantation and to discuss the obstacles with the clinical application of this technique. DESIGN: The literature on ovarian cryopreservation and transplantation was reviewed to facilitate understanding and predict future directions. The studies related to this topic were identified through MEDLINE and other bibliographic databases, focusing on the most recent developments. CONCLUSION(S): The experimental evidence for low-temperature storage of ovarian tissue is encouraging. Although restoration of fertility with cryopreserved ovarian grafts has been successful in various animals, there are uncertainties about the optimum use of stored ovarian tissue in humans. Autotransplantation appears to be promising, but the potential risk of transmitting malignant cells in women with cancer is of great concern. The maturation of primordial follicles with xenotransplantation is encouraging, but the efficacy and the safety of this method need further investigation. Furthermore, the quality of oocytes that have been matured in a host animal is unknown. The development of in vitro culture systems for oocyte maturation is still in its infancy. There are many issues to be resolved in ovarian transplantation before the full clinical use of this emerging technique. Most of all, there is an urgent need to optimize the freeze/thaw procedure and to find the means to protect grafts from ischemia-reperfusion injury. Nevertheless, ovarian transplantation should prove to be clinically useful for women at risk for premature ovarian failure.

Cellular Senescence↗

A systematic review of the reproductive system effects of metformin in patients with polycystic ovary syndrome.

OBJECTIVE: To review the effectiveness of metformin in restoring regular menstrual cycles and ovulation and achieving pregnancy in women with polycystic ovary syndrome (PCOS). DESIGN: Systematic review of pertinent studies identified using the bibliographic databases MEDLINE and EMBASE. References of selected articles identified were hand-searched for additional relevant citations. PATIENT(S): Women with PCOS undergoing treatment with metformin alone, metformin combined with other methods of ovulation induction such as clomiphene citrate (CC) or gonadotropin injections, or metformin combined with in vitro fertilization (IVF). RESULT(S): Thirty published studies were included in the overall review. Studies consisted of 12 randomized controlled trials, two cohort studies, and 16 uncontrolled descriptive studies. Due to a strong variability in the use of metformin according to study population, exposure, and outcome of interest, it was not possible to combine the data of the 12 randomized controlled trials to perform a meta-analysis. Limited data on predominately obese PCOS patients demonstrate that metformin alone improves both restoration of regular menses and spontaneous ovulation, but there are no data supporting an improvement in pregnancy rate. The addition of metformin to CC results in an improved ovulation and pregnancy rate in both unselected and CC-resistant PCOS women. There are insufficient data to make any conclusions on the effect of metformin on FSH ovulation induction or IVF. CONCLUSION(S): The effectiveness and role of metformin in the treatment of PCOS anovulatory infertility in clinical practice is difficult to assess from currently available research. Further well-designed prospective, perhaps multicenter, randomized controlled trials with the primary end point of pregnancy or live-birth rate are required.

Clomiphene↗

Surgically induced ovulation in the polycystic ovary syndrome: wedge resection revisited in the age of laparoscopy.

OBJECTIVE: To provide an up-to-date comprehensive review of published data on laparoscopic methods of ovulation induction in the polycystic ovary syndrome (PCOS). Areas to be considered include the historical background of these procedures, their outcomes as reported in the literature, and their potential adverse effects. Through the careful review of these issues, some recommendations for clinical use and further study are offered. DESIGN: Relevant studies were identified through a the search of a computerized bibliographic database of holdings in the National Library of Medicine as well as the manual scanning and cross-referencing of relevant medical journals. RESULTS: Twenty-nine relevant studies were identified in the English language literature. These studies consist almost exclusively of uncontrolled case series. Pregnancies after laparoscopic ovulation induction procedures have been reported in an average of 55% of treated subjects (range 20% to 65%). Potential advantages of laparoscopic ovulation induction over gonadotropin therapy may include possible cost savings, serial repetitive ovulatory events resulting from a single treatment, no increased risk of ovarian hyperstimulation or multiple gestation, and the prospect for a higher live birth rate owing to a seemingly lower incidence of miscarriage. Reported adverse effects include a high rate of intra-abdominal adhesion formation and a single case of iatrogenic premature menopause due to postoperative ovarian atrophy. CONCLUSIONS: The available circumstantial evidence suggests that laparoscopic procedures designed to induce ovulation may be of value in the PCOS subject who, despite an exhaustive trial of clomiphene citrate therapy, remains anovulatory and is unable or unwilling to undergo gonadotropin therapy. However, because of the risks of postoperative ovarian adhesions, carefully constructed controlled trials must be performed before these procedures can be viewed as efficacious and safe.

Abortion, Spontaneous↗

Cryopreservation of immature human oocytes and ovarian tissue: an emerging technology?

OBJECTIVE: To review the potential for cryopreserving immature follicles either in situ or after isolation from ovarian stroma and to consider the options for fertility by transplantation or in vitro follicle growth. DESIGN: The problems of storing embryos and mature (metaphase II) oocytes were considered in light of the needs of patients to protect fertility before undergoing potentially sterilizing therapy for cancer. The evidence from the experimental biology literature showing that immature oocytes (prophase I) in primordial follicles can be cryopreserved successfully and transplanted to produce fertile eggs was reviewed. The review, which was compiled from MEDLINE and other bibliographic databases, is intended to emphasize the practical opportunities for this technology and the need for future research rather than to be a comprehensive treatment of the subject. CONCLUSION(S): The disappointing results obtained with the cryopreservation of oocytes at metaphase II and ethical concerns about embryo storage are giving impetus to the banking of ovarian tissue for patients who require conservation of fertility. The numbers of needy patients are growing as long-term survivorship after high-dose chemotherapy and bone marrow transplantation rises. More speculatively, if ovarian tissue banking becomes a proven effective method, young, healthy women may request storage of ovarian biopsy samples to keep their reproductive options open in midlife when oocyte fertility is declining. Although the cryotechnology is not yet perfected, the major question now is how to use the tissue most effectively after thawing. For the present, ovarian tissue cryopreservation is still at the experimental stage, but it holds the promise of valuable applications.

Cellular Senescence↗

Variability in the accuracy of the exercise ST-segment in predicting the coronary angiogram: how good can we be?

In order to evaluate the variability in the diagnostic accuracy of the exercise electrocardiogram, a meta-analytic database derived from a review of 147 publications and a multicenter database derived from 2,826 angiographic referrals were analyzed. Wide variability in sensitivity and specificity were found from the meta-analytic review (standard deviations of 16% and 15%, respectively). No improvement in reported sensitivities and specificities has been seen over the past 22 years. The sensitivities and specifities derived from the multicenter database also showed wide variability (standard deviation 13% and 5%). These results suggest that despite obvious technologic strides in acquiring, processing, and interpreting exercise ECG signals, the accuracy of the exercise induced ST depression has not increased greatly and is difficult to ascertain a priori in a given laboratory. Individual anatomic and physiologic differences are postulated as limiting factors in the accuracy that can be obtained from this noninvasive test.

Coronary Angiography↗