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Biomedical subjects

F Song

Publications and source records attributed to F Song.

At least 19 recordsLinked to original sources
PubMed2005

Imatinib for the treatment of patients with unresectable and/or metastatic gastrointestinal stromal tumours: systematic review and economic evaluation.

OBJECTIVES: To assess the clinical and cost-effectiveness of imatinib in the treatment of unresectable and/or metastatic, KIT-positive, gastrointestinal stromal tumours (GISTs), relative to current standard treatments. DATA SOURCES: Electronic databases. REVIEW METHODS: As there were no randomised trials that have directly compared imatinib with the current standard treatment in patients with advanced GIST, this review included non-randomised controlled studies, cohort studies, and case series that reported effectiveness results of treatment with imatinib and/or other interventions in patients with advanced GIST. The effectiveness assessment was based on the comparison of results from imatinib trials and results from studies of historical control patients. Economic evaluation was mainly based on an assessment and modification (when judged necessary) of a model submitted by Novartis. RESULTS: Evidence from published uncontrolled trials involving 187 patients, and from abstracts reporting similar uncontrolled trials involving 1700 patients, indicates that approximately 50% of imatinib-treated individuals with advanced GIST experience a dramatic clinical response in terms of at least a 50% reduction in tumour mass. At present, although useful data are accumulating, it is not possible to predict which patients may respond in this way. Fifteen studies where possible GIST patients had been treated with therapies other than imatinib or best supportive care were also identified. All imatinib-treated patients experienced adverse effects, although they were relatively mild. Overall, imatinib was reported to be well tolerated. The most common serious events included unspecified haemorrhage and neutropenia. Skin rash, oedema and periorbital oedema were the common adverse events observed. Patients on the highest dose regimen (1000 mg per day in one trial) may experience dose-limiting drug toxicity. A structured assessment was carried out of the Novartis economic evaluation of imatinib for unresectable and/or metastatic GIST. The model was clearly presented and well written, its structure and input data were transparent, and the level of simplification was reasonable in terms of the objectives and data availability. However, the original Novartis model overestimated the cost-effectiveness of imatinib because of disproportion of survival and time-to-treatment failure in the imatinib arm, and the use of a possibly biased survival curve for patients in the control arm. The original Novartis model was modified to correct these two important shortcomings, which made it less sensitive to the choice of the survival curve for the control patients. According to the modified Novartis model, the estimated cost per quality-adjusted life-year (QALY) was 85,224 UK pounds (range 51,515--98,889 UK pounds) after 2 years, 41,219 UK pounds (27,331--44,236 UK pounds) after 5 years and 29,789 UK pounds (21,404--33,976 UK pounds) after 10 years. The results from a new Birmingham model were also within the range of estimates from the modified Novartis model. CONCLUSIONS: Evidence from uncontrolled studies indicates that the treatment with imatinib brings about clinically significant shrinkage of tumour mass in about half of patients with unresectable and/or metastatic, KIT-positive GIST. Results of modelling based on data from uncontrolled studies suggest that imatinib treatment improves survival in patients with unresectable and/or metastatic GIST. The economic evaluation modelling suggests that the cost per QALY gained ranges from 51,515 to 98,889 UK pounds after 2 years, from 27,331 to 44,236 UK pounds after 5 years, and from 21,404 to 33,976 UK pounds after 10 years. Further research is needed into quality of life within trials involving patients with advanced malignancy, and long-term follow-up of adverse events is needed. Subgroup analysis of which, if any, patient types have a better or worse response to imatinib is also required. Analysis of individual patient data may be a good way of exploring these issues. There are many uncertainties surrounding imatinib prescription, such as the length of time patients should be on imatinib, the dose, drug resistance and the optimum time-point in the disease course at which to give the drug. Secondary research such as an update of this systematic review and a reassessment of the model is highly recommended when ongoing trials reach completion.

Adult↗
PubMed2005

Indirect comparisons of competing interventions.

OBJECTIVES: To survey the frequency of use of indirect comparisons in systematic reviews and evaluate the methods used in their analysis and interpretation. Also to identify alternative statistical approaches for the analysis of indirect comparisons, to assess the properties of different statistical methods used for performing indirect comparisons and to compare direct and indirect estimates of the same effects within reviews. DATA SOURCES: Electronic databases. REVIEW METHODS: The Database of Abstracts of Reviews of Effects (DARE) was searched for systematic reviews involving meta-analysis of randomised controlled trials (RCTs) that reported both direct and indirect comparisons, or indirect comparisons alone. A systematic review of MEDLINE and other databases was carried out to identify published methods for analysing indirect comparisons. Study designs were created using data from the International Stroke Trial. Random samples of patients receiving aspirin, heparin or placebo in 16 centres were used to create meta-analyses, with half of the trials comparing aspirin and placebo and half heparin and placebo. Methods for indirect comparisons were used to estimate the contrast between aspirin and heparin. The whole process was repeated 1000 times and the results were compared with direct comparisons and also theoretical results. Further detailed case studies comparing the results from both direct and indirect comparisons of the same effects were undertaken. RESULTS: Of the reviews identified through DARE, 31/327 (9.5%) included indirect comparisons. A further five reviews including indirect comparisons were identified through electronic searching. Few reviews carried out a formal analysis and some based analysis on the naive addition of data from the treatment arms of interest. Few methodological papers were identified. Some valid approaches for aggregate data that could be applied using standard software were found: the adjusted indirect comparison, meta-regression and, for binary data only, multiple logistic regression (fixed effect models only). Simulation studies showed that the naive method is liable to bias and also produces over-precise answers. Several methods provide correct answers if strong but unverifiable assumptions are fulfilled. Four times as many similarly sized trials are needed for the indirect approach to have the same power as directly randomised comparisons. Detailed case studies comparing direct and indirect comparisons of the same effect show considerable statistical discrepancies, but the direction of such discrepancy is unpredictable. CONCLUSIONS: Direct evidence from good-quality RCTs should be used wherever possible. Without this evidence, it may be necessary to look for indirect comparisons from RCTs. However, the results may be susceptible to bias. When making indirect comparisons within a systematic review, an adjusted indirect comparison method should ideally be used employing the random effects model. If both direct and indirect comparisons are possible within a review, it is recommended that these be done separately before considering whether to pool data. There is a need to evaluate methods for the analysis of indirect comparisons for continuous data and for empirical research into how different methods of indirect comparison perform in cases where there is a large treatment effect. Further study is needed into when it is appropriate to look at indirect comparisons and when to combine both direct and indirect comparisons. Research into how evidence from indirect comparisons compares to that from non-randomised studies may also be warranted. Investigations using individual patient data from a meta-analysis of several RCTs using different protocols and an evaluation of the impact of choosing different binary effect measures for the inverse variance method would also be useful.

Bias↗
PubMed2004

Novel nonmatrix-metalloproteinase-mediated collagen degradation.

Matrix metalloproteinases (MMPs) and their inhibitors have long been believed to play a major role in the collagen loss seen in destructive temporomandibular joint (TMJ) disorders. This project was originally designed to examine the expression of MMPs and the tissue inhibitors of MMPs (TIMPs) by diseased human TMJ synovial fibroblasts and to determine their ability to degrade Type I collagen. Reverse transcriptase-PCR indicated that these TMJ synovial fibroblasts expressed mRNA for multiple MMPs and TIMPs. The collagen degradation assay showed that these TMJ synovial fibroblasts at passage 3 to 8 were capable of digesting the collagen underneath them on collagen-coated plates. This degradation was inhibited by GM6001, a synthetic MMP inhibitor. During passage 8 to 13, these TMJ fibroblasts were able to digest all the collagen in the wells. This degradation was completely inhibited by combining GM6001 and soybean trypsin inhibitor (STI), a serine proteinase inhibitor. The collagen cleavage activity of collected conditioned media was dramatically inhibited by STI but not by 1,10-phenanthroline, an MMP inhibitor. The data suggest that these TMJ cells utilize a MMP-dependent pathway and a novel MMP-independent pathway to digest Type I collagen.

Cells, Cultured↗
PubMed2004

Experimental studies of the material properties of the forewing of cicada (Homóptera, Cicàdidae).

Detailed investigations on the structural and mechanical properties of the forewing of the cicada were carried out. Measurement of the structures of the wings showed that the thickness of the membrane of each cell and the diameter of each vein were non-uniform in both the longitudinal and transverse directions, and their means were approximately 12.2 and 133.3 microm, respectively. However, the aspect ratios of the wings and the bodies were quite uniform and were approximately equal to 2.98 and 2.13, respectively. Based on the measured thickness, mass and area of the membranes of the cells, the mean density and the mean area density of the wing were approximately 2.3 g cm(-3) and 2.8x10(-3) g cm(-2), respectively. In addition, the diameters of the veins of the wings, including the diameters of the holes in the vein of the leading edge, were examined. The mechanical properties of the wing were investigated separately by nanoindentation and tensile testing. The results indicated that the mean Young's modulus, hardness and yield stress of the membranes of the wings were approximately 3.7 GPa, 0.2 GPa and 29 MPa, respectively, and the mean Young's modulus and strength of the veins along the direction of the venation of wings were approximately 1.9 GPa and 52 MPa, respectively. Finally, the relevant results were briefly analyzed and discussed, providing a guideline to the biomimetic design of the aerofoil materials of micro air vehicles.

Animals↗
PubMed2003

Structural and mechanical properties of the organic matrix layers of nacre.

The type of nanostructure referred to in biomineralization as a mineral bridge has been directly observed and measured in the organic matrix layers of nacre by transmission electron microscopy and scanning electron microscopy. Statistical analysis provides the geometric characteristics and a distribution law of the mineral bridges in the organic matrix layers. Experiments reveal that the nanostructures significantly influences the mechanical properties of the organic matrix layers. In addition, the mechanical analysis illustrates the effects of the nanostructures on the behaviors of the organic matrix layers, and the analytical results explain the corresponding experimental phenomena fairly well. The present study shows that the mineral bridges play a key role in the mechanical performances of the organic matrix layers of nacre. The results obtained provide a guide to the interfacial design of synthetic materials.

Animals↗
PubMed2003

Evaluating non-randomised intervention studies.

OBJECTIVES: To consider methods and related evidence for evaluating bias in non-randomised intervention studies. DATA SOURCES: Systematic reviews and methodological papers were identified from a search of electronic databases; handsearches of key medical journals and contact with experts working in the field. New empirical studies were conducted using data from two large randomised clinical trials. METHODS: Three systematic reviews and new empirical investigations were conducted. The reviews considered, in regard to non-randomised studies, (1) the existing evidence of bias, (2) the content of quality assessment tools, (3) the ways that study quality has been assessed and addressed. (4) The empirical investigations were conducted generating non-randomised studies from two large, multicentre randomised controlled trials (RCTs) and selectively resampling trial participants according to allocated treatment, centre and period. RESULTS: In the systematic reviews, eight studies compared results of randomised and non-randomised studies across multiple interventions using meta-epidemiological techniques. A total of 194 tools were identified that could be or had been used to assess non-randomised studies. Sixty tools covered at least five of six pre-specified internal validity domains. Fourteen tools covered three of four core items of particular importance for non-randomised studies. Six tools were thought suitable for use in systematic reviews. Of 511 systematic reviews that included non-randomised studies, only 169 (33%) assessed study quality. Sixty-nine reviews investigated the impact of quality on study results in a quantitative manner. The new empirical studies estimated the bias associated with non-random allocation and found that the bias could lead to consistent over- or underestimations of treatment effects, also the bias increased variation in results for both historical and concurrent controls, owing to haphazard differences in case-mix between groups. The biases were large enough to lead studies falsely to conclude significant findings of benefit or harm. Four strategies for case-mix adjustment were evaluated: none adequately adjusted for bias in historically and concurrently controlled studies. Logistic regression on average increased bias. Propensity score methods performed better, but were not satisfactory in most situations. Detailed investigation revealed that adequate adjustment can only be achieved in the unrealistic situation when selection depends on a single factor. CONCLUSIONS: Results of non-randomised studies sometimes, but not always, differ from results of randomised studies of the same intervention. Non-randomised studies may still give seriously misleading results when treated and control groups appear similar in key prognostic factors. Standard methods of case-mix adjustment do not guarantee removal of bias. Residual confounding may be high even when good prognostic data are available, and in some situations adjusted results may appear more biased than unadjusted results. Although many quality assessment tools exist and have been used for appraising non-randomised studies, most omit key quality domains. Healthcare policies based upon non-randomised studies or systematic reviews of non-randomised studies may need re-evaluation if the uncertainty in the true evidence base was not fully appreciated when policies were made. The inability of case-mix adjustment methods to compensate for selection bias and our inability to identify non-randomised studies that are free of selection bias indicate that non-randomised studies should only be undertaken when RCTs are infeasible or unethical. Recommendations for further research include: applying the resampling methodology in other clinical areas to ascertain whether the biases described are typical; developing or refining existing quality assessment tools for non-randomised studies; investigating how quality assessments of non-randomised studies can be incorporated into reviews and the implications of individual quality features for interpretation of a review's results; examination of the reasons for the apparent failure of case-mix adjustment methods; and further evaluation of the role of the propensity score.

Bias↗
PubMed2002

HLA-DR and DQ polymorphisms in bullous pemphigoid from northern China.

Bullous pemphigoid (BP) is an autoimmune disease mediated by autoantibodies against hemidesmosome components. This study used PCR-sequence-specific primers to genotype polymorphisms in HLA-DR and DQ in 25 BP patients and 57 normal controls from northern China. We found lower frequencies of DRB1*08 (DR8) and DRB1*08/DQB1*06 (DR8/DQ6) haplotypes in BP patients than in controls (4.08% vs. 15.19% and 1.54% vs. 13.82%, respectively; P < 0.05), suggesting a protective role for DR8 and DR8/DQ6 haplotypes in BP patients from northern China; there were no statistical differences among other alleles tested. This result is strikingly different from previous reports that DQB1*0301 is associated with BP in Caucasian patients and DRB1*1101, DQB1*0302, DRB1*04/DQA1*0301/DQB1*0302 and DRB1*1101/ DQA1*0505/DQB1*0302 with Japanese BP patients. Ethnic differences in the polymorphic composition of the HLA-DR and DQ genes may influence genetic susceptibility to BP.

Case-Control Studies↗
PubMed2002

A systematic review of tegaserod for the treatment of irritable bowel syndrome.

AIM: To assess the clinical effectiveness of tegaserod for the treatment of irritable bowel syndrome (IBS). DESIGN: Systematic review. SETTING: Six placebo-controlled, randomized controlled trials (RCTs) retrieved from electronic searches (Medline, Embase, FDA website) and hand-searching. MAIN OUTCOME MEASURES: Any outcome was accepted. RESULTS: In a small pharmacodynamic study, tegaserod 4 mg/day accelerated orocecal transit compared with placebo, but did not affect gastric emptying rate and colonic transit. Five placebo-controlled studies evaluated Subject's Global Assessment of gastrointestinal (GI) symptoms in predominantly female patients who fulfilled Rome criteria for constipation-predominant IBS. Responder rates were higher with tegaserod 1-24 mg/day than with placebo, although it was not possible in this review to evaluate the consistency of this effect, to fully quantify the effect size, or identify patients who may gain most benefit from this treatment. CONCLUSION: Currently published data on tegaserod for IBS are limited (two of six RCTs published in full, four as abstracts). Tegaserod may be an appropriate treatment for occasional use for relief of GI symptoms associated with constipation-predominant IBS. Further research, comparing tegaserod with alternative treatments for GI symptoms of IBS, should help define the place of this drug in therapy.

Adolescent↗
PubMed2001

Total synthesis of (-)-salicylihalamide A.

[see structure]. A 16-step synthesis of the novel cytotoxin salicylihalamide A (1E) has been achieved in 3.3% overall yield using ring closing metathesis to generate the macrolide and addition of (1Z,3Z)-hexadienylcuprate (2), which was generated in situ from ethylcuprate and acetylene, to alkenyl isocyanate 3 to form the side chain.

Bridged Bicyclo Compounds, Heterocyclic↗
PubMed2001

Rapid depletion of peripheral antigen-specific T cells in TCR-transgenic mice after oral administration of myelin basic protein.

In myelin basic protein (MBP)-specific TCR-transgenic (Tg) mice, peripheral T cells express the Valpha2.3/Vbeta8.2-Tg TCR, demonstrate vigorous proliferative responses to MBP in vitro, and can exhibit experimental autoimmune encephalomyelitis (EAE) within 5 days of pertussis toxin injection. We explored the effects of oral administration of MBP on the cellular trafficking of the MBP-specific TCR-Tg cells and the ability of oral MBP to protect Tg mice from EAE. Tg mice were fed MBP, OVA or vehicle and sacrificed at various times after feeding. An immediate and dramatic decrease in Valpha2.3/Vbeta8.2(+)-Tg cells was observed in the periphery within 1 h after feeding. By 3 days after feeding, the percentage of Tg cells increased to near control levels, but decreased again by 10 days. When MBP or vehicle-fed Tg mice were challenged for EAE at this point, disease was severe in the vehicle-fed mice and reduced in the MBP-fed mice over the 40-day observation period. In vitro studies revealed a biphasic pattern of MBP proliferative unresponsiveness and an induction of Th1 cytokines. Immunohistochemical staining showed that the number of Tg cells found in the intestinal lamina propria increased dramatically as the number of Tg cells in the periphery decreased. There was no apparent proliferation of Tg cells in the lamina propria, indicating that Tg cells trafficked there from the periphery. Taken together, these results suggest that T cell trafficking into the site of Ag deposition acts to protect the TCR-Tg mouse from EAE.

Animals↗
PubMed2001

Metal ion adducts in the structural analysis of ginsenosides by electrospray ionization with multi-stage mass spectrometry.

The effect of metal (Li+, Na+, K+, Ag+) cationization on collision-induced dissociation of ginsenosides was investigated by electrospray ionization mass spectrometry combined with multi-stage mass spectrometry (ESI-MS(n)). The fragments of sodiated and lithiated molecules give valuable structural information regarding the nature of the aglycone and the sequence and linkage information of sugar moieties. However, the number and relative abundances of fragment ions from lithiated ginsenosides are significantly greater than for the sodiated species. The K+ adducts undergo glycosidic cleavages and very limited cross-ring reactions. The silver ion adducts fragment mainly through glycosidic cleavages.

Ginsenosides↗
PubMed2001

Molecular adaptations in islets from neonatal rats reared artificially on a high carbohydrate milk formula.

Four day-old rat pups artificially raised on a high carbohydrate (HC) milk formula during their suckling period immediately develop hyperinsulinemia which persists into adulthood despite weaning onto lab chow on day 24. The present study investigates the molecular adaptations in islets isolated from neonatal rats in response to this dietary treatment during their suckling period. There is a significant increase in the level of preproinsulin mRNA and insulin biosynthesis in 12 day-old HC islets compared to islets from age-matched mother-fed (MF) control rats. Pancreatic duodenal homeobox factor-1 (PDX-1) modulates pancreatic ontogeny as well as preproinsulin gene expression in islets from neonatal rats. The mRNA level, DNA binding activity and protein content of PDX-1 are significantly increased in HC islets. The stress-activated protein kinase-2 and phosphatidylinositol 3-kinase have been reported to modulate PDX-1 activity in islets. The mRNA levels of these kinases are increased in HC islets. The mRNA level of upstream stimulatory factor (a modulator of PDX-1 gene expression) is also significantly increased in HC islets. These results indicate that the upregulation of several molecular events, including increases in the gene expression of preproinsulin, transcription factors and kinases may contribute to the chronic hyperinsulinemic state in the HC rats.

Journal Article↗
PubMed2001

Accuracy of outpatient endometrial biopsy in the diagnosis of endometrial hyperplasia.

BACKGROUND: To determine the accuracy of outpatient endometrial biopsy in diagnosing endometrial hyperplasia in women with abnormal uterine bleeding. DESIGN: Systematic quantitative review of published medical literature. DATA SOURCES: Relevant papers were identified through electronic scanning of MEDLINE (1980-1999) and EMBASE (1980-1999), manual searching of bibliography of known primary and review articles and contact with manufacturers. REVIEW METHODS: Studies were selected if accuracy of outpatient endometrial biopsy, in women with abnormal pre or postmenopausal uterine bleeding, was estimated compared to a reference standard, which was endometrial histology obtained by tissue sampling under anesthesia. Quality assessment and data extraction were performed in duplicate. Diagnostic accuracy was determined by pooled likelihood ratios (LR) for positive and negative test results for endometrial hyperplasia. RESULTS: There were 881 subjects in 8 diagnostic evaluations reported in 6 primary studies. Postmenopausal women represented 25% of the participants studied. There were 43 patients in whom outpatient sampling was inadequate. A positive test result on outpatient biopsy diagnosed endometrial hyperplasia with a pooled LR of 12.0 (95% CI 7.8-18.6) while a negative test result had a pooled LR of 0.2 (95% CI 0.1-0.3). With a positive test result, the posttest probability of endometrial hyperplasia was 57.7% (95% CI 41.1%-72.7%) while it was 2.2% (95% CI 0.9%-4.1%) with a negative test. CONCLUSION: Outpatient endometrial biopsy has modest accuracy in diagnosing endometrial hyperplasia. Therefore, additional endometrial assessment should be undertaken, especially if symptoms persist or intrauterine structural abnormalities are suspected.

Ambulatory Care↗
PubMed2001

Effectiveness and cost-effectiveness of double reading of mammograms in breast cancer screening: findings of a systematic review.

There is a lack of direct evidence on the effectiveness of double reading of breast screening mammograms within the context of national screening programmes even though about half of the countries that use mammography screening have implemented double reading. A systematic review was conducted to compare double reading with single reading of mammograms for screening accuracy, patient outcomes and costs. We searched an extensive range of electronic databases, bibliographies of studies were scanned and experts were contacted. Data extraction and quality assessment was undertaken independently by two reviewers. Estimates of the diagnostic accuracy were calculated for those studies with follow-up to identify interval cancers. Only 10 cohort studies met the inclusion criteria with reported extractable data on the effectiveness of double compared to single reading. The mix of methodologies meant that few conclusions could be drawn about the effect of double reading independent of number of views, or effects on size and type of tumours detected. Overall, double reading increases the cancer detection rate by 3-11 per 10,000 women screened and has a double impact on recall rates depending on the recall policy used. The benefit could be mainly in the detection of small cancers, and could be greatest where two readers have different strengths and weaknesses, or where readers are less experienced. Double reading can improve accuracy as compared with single reading. In particular, double reading by consensus or arbitration achieves an increase in cancer detection rate together with a reduction in the rate of women recalled for assessment. Further research should quantify the relative benefit from double reading according to recall policy and number of mammographic views, and estimate the impact on patient outcome.

Journal Article↗