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PubMedDate not supplied

Organizing the present, looking to the future: an online knowledge repository to facilitate collaboration.

BACKGROUND: Comprehensive data available in the Canadian province of Manitoba since 1970 have aided study of the interaction between population health, health care utilization, and structural features of the health care system. Given a complex linked database and many ongoing projects, better organization of available epidemiological, institutional, and technical information was needed. OBJECTIVE: The Manitoba Centre for Health Policy and Evaluation wished to develop a knowledge repository to handle data, document research Methods, and facilitate both internal communication and collaboration with other sites. METHODS: This evolving knowledge repository consists of both public and internal (restricted access) pages on the World Wide Web (WWW). Information can be accessed using an indexed logical format or queried to allow entry at user-defined points. The main topics are: Concept Dictionary, Research Definitions, Meta-Index, and Glossary. The Concept Dictionary operationalizes concepts used in health research using administrative data, outlining the creation of complex variables. Research Definitions specify the codes for common surgical procedures, tests, and diagnoses. The Meta-Index organizes concepts and definitions according to the Medical Sub-Heading (MeSH) system developed by the National Library of Medicine. The Glossary facilitates navigation through the research terms and abbreviations in the knowledge repository. An Education Resources heading presents a web-based graduate course using substantial amounts of material in the Concept Dictionary, a lecture in the Epidemiology Supercourse, and material for Manitoba's Regional Health Authorities. Confidential information (including Data Dictionaries) is available on the Centre's internal website. RESULTS: Use of the public pages has increased dramatically since January 1998, with almost 6,000 page hits from 250 different hosts in May 1999. More recently, the number of page hits has averaged around 4,000 per month, while the number of unique hosts has climbed to around 400. CONCLUSIONS: This knowledge repository promotes standardization and increases efficiency by placing concepts and associated programming in the Centre's collective memory. Collaboration and project management are facilitated.

Databases as Topic↗
PubMed1999

A novel cleavage protocol for use with Rf-encoded split pool synthesis technology: product cleavage and collection in standard 96 well format.

A novel protocol which employs commercially available, standard tools and hardware has been developed. This protocol allows for cleavage and collection of IRORI Microkan products in 96 well plate format. Typically, 640 compounds can be cleaved in a 4 hour time period using approximately 3 square feet of space. This protocol has been used successfully for the liberation of thousands of individual compounds, in single compound per well format from the solid phase. Additionally, this protocol is the first example of making IRORI Microkan technology directly compatible with standard 96 position deep well blocks.

Equipment and Supplies↗
PubMed2006

Automated SNP detection from a large collection of white spruce expressed sequences: contributing factors and approaches for the categorization of SNPs.

BACKGROUND: High-throughput genotyping technologies represent a highly efficient way to accelerate genetic mapping and enable association studies. As a first step toward this goal, we aimed to develop a resource of candidate Single Nucleotide Polymorphisms (SNP) in white spruce (Picea glauca [Moench] Voss), a softwood tree of major economic importance. RESULTS: A white spruce SNP resource encompassing 12,264 SNPs was constructed from a set of 6,459 contigs derived from Expressed Sequence Tags (EST) and by using the bayesian-based statistical software PolyBayes. Several parameters influencing the SNP prediction were analysed including the a priori expected polymorphism, the probability score (PSNP), and the contig depth and length. SNP detection in 3' and 5' reads from the same clones revealed a level of inconsistency between overlapping sequences as low as 1%. A subset of 245 predicted SNPs were verified through the independent resequencing of genomic DNA of a genotype also used to prepare cDNA libraries. The validation rate reached a maximum of 85% for SNPs predicted with either PSNP > or = 0.95 or > or = 0.99. A total of 9,310 SNPs were detected by using PSNP > or = 0.95 as a criterion. The SNPs were distributed among 3,590 contigs encompassing an array of broad functional categories, with an overall frequency of 1 SNP per 700 nucleotide sites. Experimental and statistical approaches were used to evaluate the proportion of paralogous SNPs, with estimates in the range of 8 to 12%. The 3,789 coding SNPs identified through coding region annotation and ORF prediction, were distributed into 39% nonsynonymous and 61% synonymous substitutions. Overall, there were 0.9 SNP per 1,000 nonsynonymous sites and 5.2 SNPs per 1,000 synonymous sites, for a genome-wide nonsynonymous to synonymous substitution rate ratio (Ka/Ks) of 0.17. CONCLUSION: We integrated the SNP data in the ForestTreeDB database along with functional annotations to provide a tool facilitating the choice of candidate genes for mapping purposes or association studies.

Algorithms↗
PubMed2001

Levetiracetam add-on for drug-resistant localization related (partial) epilepsy.

BACKGROUND: The majority of patients with epilepsy have a good prognosis and their seizures are well controlled by a single antiepileptic drug. However, up to 30% develop refractory seizures, particularly those with partial seizures. In this review, we summarise the current evidence regarding a new antiepileptic drug, levetiracetam, when used as an add-on treatment for drug-resistant localization related (partial) epilepsy. OBJECTIVES: To evaluate the effects of levetiracetam on seizures, side effects, quality of life and cognition, when used as an add-on treatment for patients with a drug-resistant localization related (partial) epilepsy. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group trials register, the Cochrane Controlled Trials Register (Cochrane Library Issue 2, 2000). In addition, we contacted UCB SA (makers of levetiracetam) and experts in the field to seek any ongoing studies or unpublished studies. SELECTION CRITERIA: Randomized placebo controlled add-on trials of levetiracetam in patients with a drug-resistant localization related (partial) epilepsy. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion and extracted relevant data. The following outcomes were assessed: (a) 50% or greater reduction in total seizure frequency; (b) treatment withdrawal (any reason); (c) side effects; (d) cognitive effects; (e) quality of life. Primary analyses were intention to treat. Sensitivity best and worst case analyses were also undertaken. Summary odds ratios (ORs) were estimated for each outcome. Dose response was evaluated in regression models. MAIN RESULTS: Four trials (1023 patients) were included. All four trials had data for treatment withdrawal and side effect outcomes. Three trials (904 patients) had data for 50% or greater reduction in seizure frequency. Three trials (595 patients) had data for quality of life and cognitive outcomes. The overall Odds Ratio (OR) (95% Confidence Interval (CI)) for 50% or greater reduction in total seizure frequency outcome was 3.81 (2.78,5.22). Dose regression analysis shows clear evidence that levetiracetam reduces seizure frequency with an increase in efficacy with increasing dose of levetiracetam. Approximately 15% of patients taking 1000 mg and 20-30% of patients taking 3000 mg levetiracetam per day have a 50% or greater reduction in seizure frequency. Patients were not significantly more likely to have levetiracetam withdrawn, OR (95% CI) 1.25 (0.87,1.80). The following side effects were significantly associated with levetiracetam: dizziness 2.36 (1.21, 4.61) and infection 1.82 (1.05, 3.14) whereas accidental injury was significantly associated with placebo 0.55 (0.32, 0.93). Quality of life and cognitive effect outcomes suggest that levetiracetam has a positive effect on cognition and some aspects of quality of life. REVIEWER'S CONCLUSIONS: Levetiracetam reduces seizure frequency when used as an add-on treatment for patients with a drug-resistant localization related (partial) epilepsy, and seems well tolerated. Minimum effective and maximum tolerated doses have not been identified. The trials reviewed were of 16-24 weeks duration and results cannot be used to confirm longer term effects. Our results cannot be extrapolated to monotherapy or to patients with other seizure types or epilepsy syndromes. Great care should also be taken with any attempt to apply these results to children.

Anticonvulsants↗
PubMed2003

High-throughput screening with immobilized metal ion affinity-based fluorescence polarization detection, a homogeneous assay for protein kinases.

Protein kinases are one of the most important target classes in high-throughput screening today. The use of generic assay technologies facilitates assay development for new targets and decreases the time needed for implementation of assays in robotic screening. For tyrosine kinases, several generic assay technology platforms are available. These technologies make use of high-affinity antibodies that discriminate between phosphorylated tyrosines and non-phosphorylated tyrosines. Similar generic antibodies specific for phosphoserine or phosphothreonine are lacking. Recently, a non-antibody-based fluorescence polarization assay for protein kinases has become available, called IMAP (Molecular Devices, Sunnyvale, CA). In this assay, a fluorescently labeled peptide substrate that is phosphorylated by kinase is captured on metal-derivatized nanoparticles. We have evaluated IMAP in high-throughput screening, and compared this technology with a competition fluorescence polarization immunoassay based on an antibody specific for a phosphorylated peptide substrate. A random collection of >250000 compounds was screened with the two assays. Fluorescent library compounds were identified by calculation of fluorescence intensity values from the screening data, and by assaying in the absence of fluorescent reagents. Fluorescence polarization artifacts were filtered out further by testing in an ELISA-based kinase assay. Our data show that IMAP is a robust technology for high-throughput screening of kinase targets, and suggest that it is less susceptible to fluorescence polarization artifacts than the competition fluorescence polarization immunoassay.

Artifacts↗
PubMed2003

Carbamazepine versus phenobarbitone monotherapy for epilepsy.

BACKGROUND: In developing countries, phenobarbitone is commonly used but its use in Europe and the USA has decreased due to concerns over adverse effects. Carbamazepine is recommended as the drug of choice for partial onset seizures, and there is concern that it may worsen some generalized onset seizure types. We report a review using individual patient data in which carbamazepine and phenobarbitone are compared. OBJECTIVES: To review the effects of carbamazepine compared to phenobarbitone monotherapy for people with partial onset seizures or generalized onset tonic-clonic seizures. SEARCH STRATEGY: The Cochrane Controlled trials register (Cochrane Library Issue 2, 2002); MEDLINE; EMBASE; handsearching; contacting experts and original trial investigators; contacting manufacturers of carbamazepine. SELECTION CRITERIA: Randomized or quasi-randomized, blinded or unblinded controlled trials in children or adults with partial onset seizures or generalized onset tonic-clonic seizures. DATA COLLECTION AND ANALYSIS: Outcome measures were (i) time to withdrawal of allocated treatment, (ii) time to 12 month remission, and (iii) time to first seizure. Data were analysed using a stratified logrank analysis with results expressed as hazard ratios (HR) and 95% confidence intervals (CIs), where a HR>1 indicates an event is more likely on phenobarbitone. A test for interaction between treatment and seizure type (partial versus generalized onset) was also undertaken. MAIN RESULTS: Data are available for 684 participants from four trials, representing 59% of the participants recruited into the nine trials that met our inclusion criteria. The main overall results (HR 95% CI) adjusted for seizure type were, (i) time to withdrawal 1.63(1.23 to 2.15), (ii) time to 12 month remission 0.87(0.65 to 1.17), (iii) time to first seizure 0.85(0.68 to 1.05). The review suggests that time to withdrawal is significantly improved with carbamazepine compared to phenobarbitone. No overall difference between drugs is identified for the outcomes 'time to 12 month remission' and 'time to first seizure'. Statistical heterogeneity was not encountered. An interaction between treatment and seizure type, confirmed statistically, was identified for time to first seizure, where phenobarbitone was favoured for partial onset seizures and carbamazepine for generalized onset tonic-clonic seizures. REVIEWER'S CONCLUSIONS: We found no overall difference between carbamazepine and phenobarbitone for time to 12 month remission or time to first seizure, however, subgroup analyses for time to first seizure suggest an advantage with phenobarbitone for partial onset seizures and a clinical advantage with carbamazepine for generalized onset tonic-clonic seizures. Phenobarbitone is significantly more likely to be withdrawn, indicating that it is less well tolerated than carbamazepine.

Adult↗
PubMed2003

Combined corticosteroid and longacting beta-agonist in one inhaler for chronic obstructive pulmonary disease.

BACKGROUND: Long-acting beta-agonists and inhaled corticosteroids have been recommended in guidelines for the treatment of chronic obstructive pulmonary disease. However, they have only been available until recently via separate administration. They have been developed in order to facilitate adherence to medication regimens, and to improve efficacy. OBJECTIVES: To assess the efficacy of combined inhaled corticosteroid and long-acting beta-agonist preparations in the treatment of adults with chronic obstructive pulmonary disease. SEARCH STRATEGY: We searched the Cochrane Airways Group chronic obstructive pulmonary disease (COPD) trials register (March 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2003), LILACS (all years to March 2003) and reference lists of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: Studies were included if they were randomised, with adequate blinding procedures in place. Studies could compare a combined inhaled corticosteroids and long-acting beta-agonist preparation with either component preparation or placebo. Studies comparing different members of each class of combined therapies were included DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Four randomised trials with 2986 participants were included. Two different combination preparations (fluticasone/salmeterol and budesonide/formoterol) were studied in the trials. No meta-analysis on clinical outcomes was possible due to different outcome assessment across studies. All studies demonstrated a reduction in exacerbation rates versus placebo. Budesonide/formoterol was more effective than formoterol in reducing exacerbations in one study from 1.84 to 1.42 exacerbations per year. Fluticasone/salmeterol did not significantly reduce exacerbations compared with either of its component treatments. Fluticasone/salmeterol led to better quality of life compared with placebo (two studies), although there were conflicting results when compared with inhaled corticosteroid alone (two studies). There was no significant difference between fluticasone/salmeterol and long-acting beta-agonist (two studies). Budesonide/formoterol led to statistically significant differences in quality of life compared with placebo, but not when compared with component inhaled corticosteroid or beta-agonist (one study). REVIEWER'S CONCLUSIONS: For the primary outcome of exacerbations, budesonide/formoterol had a modest advantage over a component medication, formoterol, in a single trial, but fluticasone/salmeterol did not result in a significant reduction in exacerbations compared to either of its components. The combination of steroids and long-acting beta-agonist in one inhaler was effective in improving symptoms compared with placebo and on certain clinical outcomes compared with one of the individual components alone. In order to draw firmer conclusions about the effects of combination therapy in a single inhaler more data are necessary, including the assessment of the comparative effects with separate administration of the two drugs in double-dummy trials.

Adrenergic beta-Agonists↗
PubMed2006

Vaccines for preventing malaria (pre-erythrocytic).

BACKGROUND: Vaccines against all stages of the malaria parasite are in development, mainly for Plasmodium falciparum, which causes the most serious form of malaria. Pre-erythrocytic vaccines act to prevent or delay a malaria attack by attacking the sporozoite and liver stages before the parasite reaches the bloodstream. OBJECTIVES: To assess the efficacy and safety of pre-erythrocytic malaria vaccines against any type of human malaria. SEARCH STRATEGY: In March 2006, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE, EMBASE, LILACS, and the Science Citation Index. We also searched conference proceedings and reference lists of articles, and contacted organizations and researchers in the field. SELECTION CRITERIA: Randomized controlled trials comparing pre-erythrocytic vaccines with placebo, control vaccine, or routine antimalarial control measures in people of any age receiving an artificial challenge or natural exposure to malaria infection. DATA COLLECTION AND ANALYSIS: Both authors independently assessed trial quality and extracted data. Results of meta-analyses were expressed as relative risks with 95% confidence intervals (CI) using an intention-to-treat analysis. MAIN RESULTS: Nine safety and efficacy trials, and two safety trials, with over 3000 participants were included. In semi-immune children, RTS,S vaccine reduced clinical episodes of malaria by 26% (95% CI 13% to 37%) and severe malaria by 58% (95% CI 15% to 79%) for up to 18 months. Prevalence of parasitaemia was also reduced by 26% (95% CI 11% to 38%) at six months after immunization. RTS,S also reduced clinical malaria episodes by 63% (95% CI 18% to 83%) in semi-immune adult men in the second year of follow up after a booster dose. No severe adverse events were judged to be related to RTS,S vaccine, although the frequencies of injection site pain, swelling, arm motion limitation, headache, and malaise were increased in the vaccine groups. There was no evidence for effect of the CS-NANP vaccines (307 participants, 3 trials), CS102 peptide vaccine (14 participants, 1 trial), or the ME-TRAP vaccine (372 participants, 1 trial). AUTHORS' CONCLUSIONS: RTS,S vaccine was effective in preventing a significant number of clinical malaria episodes, including good protection against severe malaria in children for 18 months. No severe adverse events were attributable to the vaccine. Progression of this vaccine towards licensing is justified while efforts to increase its efficacy continue. The other vaccines do not look promising and further research is a priority.

Adult↗
PubMed2003

Selection criteria for drug-like compounds.

The fast identification of quality lead compounds in the pharmaceutical industry through a combination of high throughput synthesis and screening has become more challenging in recent years. Although the number of available compounds for high throughput screening (HTS) has dramatically increased, large-scale random combinatorial libraries have contributed proportionally less to identify novel leads for drug discovery projects. Therefore, the concept of 'drug-likeness' of compound selections has become a focus in recent years. In parallel, the low success rate of converting lead compounds into drugs often due to unfavorable pharmacokinetic parameters has sparked a renewed interest in understanding more clearly what makes a compound drug-like. Various approaches have been devised to address the drug-likeness of molecules employing retrospective analyses of known drug collections as well as attempting to capture 'chemical wisdom' in algorithms. For example, simple property counting schemes, machine learning methods, regression models, and clustering methods have been employed to distinguish between drugs and non-drugs. Here we review computational techniques to address the drug-likeness of compound selections and offer an outlook for the further development of the field.

Algorithms↗
PubMed2002

Expression of homeobox genes in cervical cancer.

OBJECTIVE: Members of the homeobox (HB) gene superfamily encode transcription factors crucial for development and may be associated with tumorigenesis. In this study, we aimed to develop a procedure to survey the expression of the dispersed-type HB genes in cervical cancer cells. METHODS: Nineteen sets of degenerate primers were designed based on conserved homeodomains of known dispersed-type HB genes. A cDNA library derived from HeLa, a cervical cancer cell line, was used. Two successive rounds of PCR were performed using a combination of the HB degenerate primers and a primer recognizing the flanking sequence of the vector used in the cDNA library construction. RESULTS: On cloning and sequence analysis of the PCR fragments generated, 10 known and 3 putative novel HB genes were detected in HeLa. RT-PCR expression analysis further showed that HOXD9 and ATBF1 were differentially expressed in cancer cells and not in normal cervix. CONCLUSIONS: Our data demonstrate the feasibility of using degenerate primers in PCR experiments in a collective analysis of complex gene families. Our data indicate that HOXD9 and ATBF1 are expressed in cervical cancer, but not in normal cervix.

Amino Acid Sequence↗
PubMedDate not supplied

Searching for biomedical information on the World Wide Web.

The rapid growth of biomedical information available via the Internet and its most popular retrieval system, the World Wide Web, has fostered active research and development directed toward locating resources that are appropriate for answering specific queries. The goal is to create tools that optimize information retrieval (as measured by two quantities, precision and recall) while minimizing the effort required by the user. Existing Web retrieval tools can be divided into the following groups: manually maintained topical lists; automatically generated word-based indices; software agents and multi-index searching aids; network cataloging methods; and miscellaneous hybrid and newer approaches. Improvements in current methods should arise from further research into: methods of describing objects on the Web; improved ways of searching for (and within) collections of documents as opposed to single documents; the ability to search for fielded documents; and ways to describe resources that span intra- and interdisciplinary as well as cross-cultural linguistic differences. For this last problem, the U.S. National Library of Medicine's Unified Medical Language System (UMLS) will be of great help. As online information retrieval improves, efforts are underway to improve the online information itself; quality control over content is being addressed as the peer-review systems of traditional printed journals migrate into the realm of electronic publication.

Abstracting and Indexing↗
PubMed2003

Assessment of bacterial community structure in the deep sub-seafloor biosphere by 16S rDNA-based techniques: a cautionary tale.

Investigations into the deep marine environment have demonstrated the presence of a significant microbial biomass buried deep within sediments on a global scale. It is now believed that this deep biosphere plays a major role in the global cycling of elements and contains a large reservoir of organic carbon. This paper reports the development of a DNA extraction protocol that addresses the particular problems faced in applying molecular ecological techniques to samples containing very low biomass. Sediment samples were collected from different geographical locations within the Pacific Ocean and include the Ocean Drilling Program (ODP) Leg 190, Nankai Trough Accretionary Prism. Seven DNA extraction protocols were tested and a commercially available DNA extraction kit with modifications was shown to produce higher yields of polymerase chain reaction (PCR)-amplifiable DNA than standard laboratory methods. Denaturing gradient gel electrophoresis (DGGE) analysis of 16S rRNA gene diversity revealed that template DNA from these extremely low biomass sediment samples was susceptible to PCR bias and random amplification. We propose that it is essential to screen 16S rRNA gene products for bacterial diversity by DGGE or other rapid fingerprinting methods, prior to their use in establishing a representative clone library of deep sub-seafloor bacteria. This represents a cautionary approach to analysis of microbial diversity in such sub-seafloor ecosystems.

Bacteria↗
PubMed2005

Oral anti-oestrogens and medical adjuncts for subfertility associated with anovulation.

BACKGROUND: Infertility due to anovulation is a common problem in women. The first line oral treatment is with anti-oestrogens, such as clomiphene citrate. Unfortunately there may be resistance and alternative and adjunctive treatments have been developed. These include tamoxifen, dexamethasone, bromocriptine and aromatase inhibitors (AIs). OBJECTIVES: To determine the relative effectiveness of anti-oestrogen agents, with or without medical adjuncts, in women with WHO group 2 anovulation. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trial register (searched 5th July 2004), CENTRAL (The Cochrane Library Issue 2 2004), MEDLINE (1966 to June 2004) and EMBASE (1980 to June 2004) for identification of relevant randomised controlled trials (RCTs). Additionally the United Kingdom National Institute for Clinical Excellence (NICE) guidelines and the references of relevant reviews and RCTs were searched. SELECTION CRITERIA: RCTs that compare oral anti-oestrogen agents for ovulation induction (alone or in conjunction with medical adjuncts) in anovulatory subfertility, were considered for inclusion in the review. Metformin and other insulin sensitizing agents were not included. Hyperprolactinaemic infertility was not included. DATA COLLECTION AND ANALYSIS: Data extraction and quality assessment was done independently by two reviewers. The primary outcome was live birth, secondary outcomes were: pregnancy, ovulation, miscarriage, multiple pregnancy, overstimulation, ovarian hyperstimulation syndrome and patient reported adverse effects. MAIN RESULTS: Twelve RCTs were found and included in this review. No trials reported live birth as an outcome. Miscarriage and multiple pregnancy rates were poorly reported. Clomiphene was shown to be effective in increasing pregnancy rate when compared to placebo (fixed OR 5.8, 95% CI 1.6 to 21.5; NNT 5.9, 95% CI 3.6 to 16.7). No evidence of a difference in effect was found between clomiphene and tamoxifen (fixed OR 1.0, 95% CI 0.5 to 2.1). The use of clomiphene in combination with tamoxifen did not find any evidence of effect on pregnancy rate when compared to clomiphene alone (fixed OR 3.3, 95% CI 0.1 to 91.6). The comparison between two AIs (letrozole and anastrozole) did not find any evidence of a difference in effect on pregnancy rate (fixed OR 1.9, 95% CI 0.4 to 8.9). For the intervention of clomiphene plus ketoconazole vs clomiphene no evidence of a difference in effect for pregnancy rate was found (fixed OR 2.4, 95% CI 0.9 to 6.4). For clomiphene plus bromocriptine vs clomiphene no evidence of a difference in effect on pregnancy rate was found (fixed OR 1.0, 95% CI 0.3 to 3.0) rates. However, clomiphene plus dexamethasone treatment resulted in a significant improvement in the pregnancy rate (fixed OR 11.3, 95% CI 5.3 to 24.0; NNT 2.7, 95% CI 2.1 to 3.6) when compared to clomiphene alone as did clomiphene plus pretreatment with combined oral contraceptives (fixed OR 27.2, 95% CI 3.1 to 235.0; NNT 2.0, 95% CI 1.4 to 3.4). AUTHORS' CONCLUSIONS: This review shows evidence supporting the effectiveness of the current first line treatment, clomiphene citrate. No evidence of a difference in effect was found between clomiphene and tamoxifen. The use of dexamethasone as an adjunct to clomiphene therapy appears promising as do combined oral contraceptives. This review has highlighted a gap in the literature on effects of these drugs on outcomes such as miscarriage rate. Evidence in favour of these interventions is flawed. RCTs of adequate power and of high methodological quality are required for the older treatments such as clomiphene, alone and with medical adjuncts, and also for the newer drugs such as the AIs.

Anovulation↗
PubMed2002

Nutrition support for bone marrow transplant patients.

BACKGROUND: Bone marrow transplantation involves the administration of toxic chemotherapy and infusion of marrow cells. After treatment, patients can develop a poor appetite, mucositis and gastrointestinal failure, leading to malnutrition. To prevent this, parenteral nutrition (PN) support is the first choice but is associated with an increased risk of infection. Enteral nutrition (EN) is an alternative, as is the addition of substrates e.g. glutamine to enteral and parenteral solutions. However, the relative effectiveness of these treatments is not clear. OBJECTIVES: To determine the efficacy of EN or PN support for patients receiving a bone marrow transplant. SEARCH STRATEGY: Trials were identified by searching the Cochrane Library (Issue 4, 2000 ), MEDLINE (1966-2000), EMBASE (1988-2000) and CINAHL (1982-2000 ). Reference lists of identified trials and conference proceedings were searched for relevant reports. Date of the most recent search: 2000. SELECTION CRITERIA: RCTs that compared one form of nutrition support with another, or control, for bone marrow transplant patients were included. DATA COLLECTION AND ANALYSIS: Thirty five reports were identified, 11 were excluded. Two reviewers extracted data from 24 studies; 16 were allocated to four interventions: oral glutamine versus placebo; PN and glutamine versus standard PN; PN versus IV hydration; PN versus EN. Eight studies were other interventions. Data were collected on participants' characteristics; adverse effects; neutropaenia; % change in body weight; graft versus host disease; and survival. Trialists were contacted for unreported data. MAIN RESULTS: Two studies (82 subjects) found that glutamine mouthwash reduced days of neutropaenia (6.82 days, 95% CI (1.67-11.98) p=0.009) compared with placebo. Three studies (103 subjects) showed that patients receiving PN with glutamine had a reduced hospital stay, 6.62 d (95% CI 3.47, 9.77, P=0.00004) compared with patients receiving standard PN. Two studies (73 subjects) indicated that patients receiving PN plus glutamine had a reduced incidence of positive blood cultures (OR 0.23, 95% CI 0.08-0.65, p=0.006) compared to those receiving standard PN. One study, (25 subjects) showed patients receiving PN had a higher incidence of line infections (odds ratio 21.23, 95% CI 4.15,108.73, P=0.0002) compared to those receiving standard IV fluids. There were no evaluable data to compare PN with EN. REVIEWER'S CONCLUSIONS: Lack of evaluable data means that the relative effectiveness of EN versus PN cannot be evaluated. Further studies and missing data from completed trials need to be retrieved. Studies comparing PN with glutamine versus standard PN suggest that patients leave hospital earlier, and experience a reduced incidence of positive blood cultures, than those receiving standard PN. Patients with gastrointestinal failure should consider PN with the addition of glutamine if enteral feeding is not possible.

Bone Marrow Transplantation↗
PubMed2004

Perioperative fluid volume optimization following proximal femoral fracture.

BACKGROUND: Proximal Femoral Fracture (PFF) or 'hip fracture' is a frequent injury, and adverse outcomes are common. Several factors suggest the importance of developing techniques to optimize intravascular fluid volume. These may include protocols that enhance the efficacy of clinicians' assessments, invasive techniques such as oesophageal Doppler or central venous pressure monitoring, or advanced non-invasive techniques such as plethysmographic pulse volume determination. OBJECTIVES: To determine the optimal method of fluid volume optimization for adult patients undergoing surgical repair of PFF. Comparisons of fluid types, of blood transfusion strategies or of pharmacological interventions are not considered in this review. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library, issue 4, 2003), MEDLINE (1985 to 2003), EMBASE (1985 to 2003), and bibliographies of retrieved articles. Relevant journals and conference proceedings were handsearched. SELECTION CRITERIA: Randomized controlled studies comparing a fluid optimization intervention with normal practice or with another fluid optimization intervention, in patients following PFF undergoing surgery of any type under anaesthesia of any type. DATA COLLECTION AND ANALYSIS: Searches and exclusion of clearly irrelevant articles were performed by one reviewer. Two reviewers examined independently the remaining studies, extracting study quality and results data. A wide range of short- and long-term outcome data were sought. Studies were excluded if they did not meet selection criteria or if results were likely to be biased. Due to inconsistent data reporting, combination of data was not generally possible. MAIN RESULTS: Searches identified four trials, of which two studies, randomizing a total of 130 patients, were of adequate quality and addressed the review question. Both studies were of invasive advanced haemodynamic monitoring, either oesophageal Doppler ultrasonography or central venous pressure monitoring, during the intraoperative period only. In both, invasive monitoring led to significant increases in fluid volumes infused and reductions in length of hospital stay. The pooled Peto odds ratio for in-hospital fatality was 1.44 (95% confidence interval 0.45-4.62). Neither study followed patients beyond hospital discharge or assessed functional outcomes. No serious complications were directly attributable to the interventions. There were no studies of protocol-guided fluid optimization or of advanced non-invasive techniques. REVIEWER'S CONCLUSIONS: Invasive methods of fluid optimization during surgery may shorten hospital stay, but their effects on other important, patient-centred, longer-term outcomes are uncertain. Adverse effects on fatality cannot be excluded. Other fluid optimization techniques have not been evaluated. The lack of randomized studies of adequate quality addressing this important question is disappointing. More research is needed.

Femoral Fractures↗
PubMed2005

Screening for amblyopia in childhood.

BACKGROUND: Amblyopia is a reversible deficit of vision that has to be treated within the sensitive period for visual development. Screening programmes have been set up to detect this largely asymptomatic condition and refer children for treatment while an improvement in vision is still possible. The value of such programmes and the optimum protocol for administering them remain controversial. OBJECTIVES: The objective of this review was to evaluate the effectiveness of vision screening in reducing the prevalence of amblyopia. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Group Trials Register, on The Cochrane Library Issue 2, 2005, MEDLINE (1966 to May 2005 week 1) and EMBASE (1980 to 2005 week 19). No language restrictions were placed on these searches. No handsearching was done. SELECTION CRITERIA: We planned to analyse data from randomised controlled trials and cluster-randomised trials comparing the prevalence of amblyopia in screened versus unscreened populations. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study abstracts identified by the electronic searches. Full text copies of appropriate studies were obtained and, where necessary, authors were contacted. No data were available for analysis and no meta-analysis was performed. MAIN RESULTS: Despite the large amount of literature available regarding vision screening no trials designed to compare the prevalence of amblyopia in screened versus unscreened populations were found. Data currently under preparation may be available for updates to the review. AUTHORS' CONCLUSIONS: The lack of data from randomised controlled trials makes it difficult to analyse the impact of existing screening programmes on the prevalence of amblyopia. The absence of such evidence cannot be taken to mean that vision screening is not beneficial; simply that this intervention has not yet been tested in robust trials. To facilitate such trials normative data on age-appropriate vision tests need to be available and a consensus reached regarding the definition of amblyopia. In addition, the consequences of living with untreated amblyopia have yet to be quantified and a cost-benefit analysis carried out.

Amblyopia↗
PubMed2026

Sechium edule: Phytochemistry, Biological Activities, Potential Health Effects, Food-Industry Applications, and Future Perspectives.

Sechium edule (Jacq.) Sw. (chayote), a neglected and underutilized Cucurbitaceae crop widely cultivated across tropical and subtropical regions, has drawn growing interest as a source of health-promoting food components. This review critically synthesizes studies published between 2000 and 2026 on its botanical features, genome characterization, nutritional value, phytochemistry, bioactivities, safety, and food-industry applications, based on literature retrieved from PubMed, Scopus, Web of Science, ScienceDirect, and the Cochrane Library. Different plant parts (fruits, leaves, seeds, tuberous roots, and peels) contain diverse bioactive compounds, including flavonoids, phenolic acids, cucurbitacins, pectin polysaccharides, and carotenoids. Reported bioactivities include antioxidant, anti-inflammatory, hypoglycemic, cardioprotective, antiproliferative, and geroprotective effects, mediated in part through Nrf2-mediated antioxidant signaling and sirtuin (SIRT1/3/5/6) upregulation. Notably, a systematic meta-analysis demonstrated a significant reduction in serum glucose (MD = -20.56; 95% CI: -29.35 to -11.77) and HbA1c following three months of chayote intake in patients with metabolic syndrome and type 2 diabetes. Industrially, chayote has been developed into fermented products, starch- and peel-derived bioactive films, ultrasound-extracted pectin, α-amylase inhibitory seed protein isolates, and probiotic encapsulation systems. Recent genomic work has further revealed a chromosome-level genome assembly, whole-genome duplication events, and a domestication history tracing to Mexico's Oaxaca region. Collectively, this evidence positions chayote as a promising underutilized resource for food, nutraceutical, and biomedical use, while highlighting key gaps: the need for standardized clinical trials, bioavailability studies, and comprehensive safety evaluation.

Sechium edule↗
PubMed1994

Document needs in a rural GRATEFUL MED outreach project.

An analysis of documents provided to eight rural Illinois hospital sites during a GRATEFUL MED outreach project involving end-user searching revealed significant patterns that have implications for collection development and information services in small, underserved hospitals. Document requests were analyzed by user groups making the requests, subject matter, inclusion on the Brandon/Hill lists and in Abridged Index Medicus, and publication date. Of the 359 documents requested, 86% came from health professional groups other than physicians and nurses. Eighty-five percent of all requests came from two sites that had active project-trained intermediaries, with most requests forwarded by the intermediaries. Subject analysis revealed a strong need for administrative and allied health information in addition to clinical information. Fewer than half of the titles on the recommended lists were requested during the project. Most documents requested had been published in the past five years. Introduction of end-user searching is not the complete answer to improved information access at small hospitals; the authors conclude that basic collections and library personnel are still needed locally to respond effectively to health professionals' information needs.

Documentation↗