SEARCH · Search PubMed

Results for “reference databases”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 973 records · Page 54Linked to original sources

PubMed1996

Implementation of a reference management system, MacRefer, under HyperCard.

We have developed a reference management system, MacRefer, using HyperTalk on Macintosh personal computers. Using this program, one can automatically acquire data from databases created by EndNote Plus and from OVID- or Medlar-formatted records downloaded via an online use of Medline. The MacRefer's capability of formatting bibliographic database in user-defined formats is comparable with the exemplified bibliography maker, EndNote Plus. Moreover, MacRefer has several competitive features, which are insufficiently equipped with EndNote Plus. For example, MacRefer is capable of (1) maintaining subsets within a database, (2) executing complex, structured searches combining up to nine keywords for any data field with the results and search conditions preserved, and (3) easily browsing (a portion of) reference database. Although MacRefer cannot be recognized as an absolute alternative of EndNote Plus because of several limitations inherent to HyperCard, the compensatory use of these two programs will expand the personal utilization of bibliographic databases.

Computers↗

PubMed2000

Depression and poor glycemic control: a meta-analytic review of the literature.

OBJECTIVE: Depression is common among patients with diabetes, but its relationship to glycemic control has not been systematically reviewed. Our objective was to determine whether depression is associated with poor glycemic control. RESEARCH DESIGN AND METHODS: Medline and PsycINFO databases and published reference lists were used to identify studies that measured the association of depression with glycemic control. Meta-analytic procedures were used to convert the findings to a common metric, calculate effect sizes (ESs), and statistically analyze the collective data. RESULTS: A total of 24 studies satisfied the inclusion and exclusion criteria for the meta-analysis. Depression was significantly associated with hyperglycemia (Z = 5.4, P < 0.0001). The standardized ES was in the small-to-moderate range (0.17) and was consistent, as the 95% CI was narrow (0.13-0.21). The ES was similar in studies of either type 1 or type 2 diabetes (ES 0.19 vs. 0.16) and larger when standardized interviews and diagnostic criteria rather than self-report questionnaires were used to assess depression (ES 0.28 vs. 0.15). CONCLUSIONS: Depression is associated with hyperglycemia in patients with type 1 or type 2 diabetes. Additional studies are needed to establish the directional nature of this relationship and to determine the effects of depression treatment on glycemic control and the long-term course of diabetes.

Adult↗

PubMed2000

Evidence-based medicine in nephrology: identifying and critically appraising the literature.

BACKGROUND: Uncertainties about best management of end-stage renal disease (ESRD) are reflected in wide variations in practice. Systematic reviews aim to reduce uncertainty by strengthening the evidence base for clinical practice, allowing estimation of the benefits and risks of particular interventions, whilst minimizing the potential for bias. This paper describes the methods and conduct of six systematic reviews of aspects of the management of ESRD, and the yield in terms of trials found. METHODS: Our methodology was based on that recommended by the Cochrane Collaboration (an international initiative set up to perform and disseminate systematic reviews of health care). It involved a systematic search of electronic databases and bibliographic reference lists, together with handsearching of Kidney International for studies relevant to the management of ESRD, followed by a systematic assessment of study quality. RESULTS: Around 12,000 abstracts were assessed which had been identified from electronic sources. Of these, 2085 (18%) were deemed to be reports of possible randomized or quasi-randomized controlled trials relevant to the management of ESRD. Three hundred and forty were relevant to the six specific reviews, and after assessment of the full manuscripts, 39 studies were finally included in our reviews. Reports of a further nine trials, which were identified from other sources, were also included. The broad search adopted allowed the parallel development of a register of trials of all aspects of the management of ESRD. CONCLUSIONS: This study has demonstrated that the methodology of systematic reviews, as promoted by the Cochrane Renal Group, is feasible but has significant resource implications. The development of a register of randomized controlled trials (RCTs) related to the management of ESRD will facilitate this form of research in the future.

Databases as Topic↗

PubMed2001

The prevalence of comorbid depression in adults with diabetes: a meta-analysis.

OBJECTIVE: To estimate the odds and prevalence of clinically relevant depression in adults with type 1 or type 2 diabetes. Depression is associated with hyperglycemia and an increased risk for diabetic complications; relief of depression is associated with improved glycemic control. A more accurate estimate of depression prevalence than what is currently available is needed to gauge the potential impact of depression management in diabetes. RESEARCH DESIGN AND METHODS: MEDLINE and PsycINFO databases and published references were used to identify studies that reported the prevalence of depression in diabetes. Prevalence was calculated as an aggregate mean weighted by the combined number of subjects in the included studies. We used chi(2) statistics and odds ratios (ORs) to assess the rate and likelihood of depression as a function of type of diabetes, sex, subject source, depression assessment method, and study design. RESULTS: A total of 42 eligible studies were identified; 20 (48%) included a nondiabetic comparison group. In the controlled studies, the odds of depression in the diabetic group were twice that of the nondiabetic comparison group (OR = 2.0, 95% CI 1.8-2.2) and did not differ by sex, type of diabetes, subject source, or assessment method. The prevalence of comorbid depression was significantly higher in diabetic women (28%) than in diabetic men (18%), in uncontrolled (30%) than in controlled studies (21%), in clinical (32%) than in community (20%) samples, and when assessed by self-report questionnaires (31%) than by standardized diagnostic interviews (11%). CONCLUSIONS: The presence of diabetes doubles the odds of comorbid depression. Prevalence estimates are affected by several clinical and methodological variables that do not affect the stability of the ORs.

Adult↗

PubMed2005

CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients: a HuGEnet systematic review and meta-analysis.

PURPOSE: Two common variant alleles of the cytochrome CYP2C9 (CYP2C9*2 and CYP2C9*3) lead to reduced warfarin metabolism in vitro and in vivo. The study objective was to examine the strength and quality of existing evidence about CYP2C9 gene variants and clinical outcomes in warfarin-treated patients. METHODS: The study was a systematic review and meta-analysis. Multiple electronic databases were searched, references identified from bibliographies were sought, and experts and authors of primary studies were also contacted. Strict review inclusion criteria were determined. Three reviewers independently extracted data using prepiloted proformas. RESULTS: In all, 11 studies meeting review inclusion criteria were identified (3029 patients). Nine were included in the meta-analyses (2775 patients). Random effects meta-analyses were performed; statistical heterogeneity and inconsistency was assessed. Twenty percent of patients studied carry a variant allele: CYP2C9*2 12.2% (9.7%-15.0%) and CYP2C9*3, 7.9% (6.5%-9.7%). Mean difference in daily warfarin dose: for CYP2C9*2, the reduction was 0.85 mg (0.60-1.11 mg), a 17% reduction. For CYP2C9*3, the reduction was 1.92 mg (1.37-2.47 mg), a 37% reduction. For CYP2C9*2 or *3, the reduction was 1.47 mg (1.24-1.71 mg), a 27% reduction. The relative bleeding risk for CYP2C9*2 was 1.91 (1.16-3.17) and for CYP2C9*3 1.77 (1.07-2.91). For either variant, the relative risk was 2.26 (1.36-3.75). CONCLUSIONS: Patients with CYP2C9*2 and CYP2C9*3 alleles have lower mean daily warfarin doses and a greater risk of bleeding. Testing for gene variants could potentially alter clinical management in patients commencing warfarin. Evidence for the clinical utility and cost-effectiveness of genotyping is needed before routine testing can be recommended.

Alleles↗

PubMed2000

Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome.

OBJECTIVES: Irritable bowel syndrome is the most common gastrointestinal diagnosis. The symptoms of irritable bowel syndrome are similar to those of small intestinal bacterial overgrowth. The purpose of this study was to test whether overgrowth is associated with irritable bowel syndrome and whether treatment of overgrowth reduces their intestinal complaints. METHODS: Two hundred two subjects in a prospective database of subjects referred from the community undergoing a lactulose hydrogen breath test for assessment of overgrowth were Rome I criteria positive for irritable bowel syndrome. They were treated with open label antibiotics after positive breath test. Subjects returning for follow-up breath test to confirm eradication of overgrowth were also assessed. Subjects with inflammatory bowel disease, abdominal surgery, or subjects demonstrating rapid transit were excluded. Baseline and after treatment symptoms were rated on visual analog scales for bloating, diarrhea, abdominal pain, defecation relief, mucous, sensation of incomplete evacuation, straining, and urgency. Subjects were blinded to their breath test results until completion of the questionnaire. RESULTS: Of 202 irritable bowel syndrome patients, 157 (78%) had overgrowth. Of these, 47 had follow-up testing. Twenty-five of 47 follow-up subjects had eradication of small intestinal bacterial overgrowth. Comparison of those that eradicated to those that failed to eradicate revealed an improvement in irritable bowel syndrome symptoms with diarrhea and abdominal pain being statistically significant after Bonferroni correction (p < 0.05). Furthermore, 48% of eradicated subjects no longer met Rome criteria (chi2 = 12.0, p < 0.001). No difference was seen if eradication was not successful. CONCLUSIONS: Small intestinal bacterial overgrowth is associated with irritable bowel syndrome. Eradication of the overgrowth eliminates irritable bowel syndrome by study criteria in 48% of subjects.

Adult↗

PubMed2001

STRBase: a short tandem repeat DNA database for the human identity testing community.

The National Institute of Standards and Technology (NIST) has compiled and maintained a Short Tandem Repeat DNA Internet Database (http://www.cstl.nist.gov/biotech/++ +strbase/) since 1997 commonly referred to as STRBase. This database is an information resource for the forensic DNA typing community with details on commonly used short tandem repeat (STR) DNA markers. STRBase consolidates and organizes the abundant literature on this subject to facilitate on-going efforts in DNA typing. Observed alleles and annotated sequence for each STR locus are described along with a review of STR analysis technologies. Additionally, commercially available STR multiplex kits are described, published polymerase chain reaction (PCR) primer sequences are reported, and validation studies conducted by a number of forensic laboratories are listed. To supplement the technical information, addresses for scientists and hyperlinks to organizations working in this area are available, along with the comprehensive reference list of over 1300 publications on STRs used for DNA typing purposes.

Databases, Factual↗

PubMed2001

Haloperidol for agitation in dementia.

BACKGROUND: Agitation includes wandering, crying out, abusive vocalization, and assaultive behavior and occurs in up to 70% of patients with dementia. Although the neuroleptic haloperidol has been used for decades to control disruptive behavior in psychotic and demented patients, the effectiveness of this drug for agitated dementia remains in question. The first meta-analysis on the effectiveness of haloperidol for agitated dementia, published in 1990, was limited in scope and was unable to provide clear guidelines for the use of haloperidol for demented patients who are agitated. Meta-analyses in 1998 and 2000 examined haloperidol compared with other neuroleptics as well as with placebo and omitted a number of databases, including non-English language publications. To determine the effect of haloperidol, compared with placebo, in the control of agitated dementia and to make recommendations for future research in this area a more widely based, yet more highly focussed review was carried out. OBJECTIVES: The main objective was to determine whether evidence supports the use of haloperidol to treat agitation in demented patients. SEARCH STRATEGY: The CDCIG Specialized Register was searched to identify all available reports on haloperidol treatment of agitated dementia. SELECTION CRITERIA: We examined randomized, placebo-controlled trials, with concealed allocation, where subjects' dementia and agitation were assessed. Trials involving treatment of less than one week were not included. DATA COLLECTION AND ANALYSIS: 1. Two reviewers extracted data from included trials. 2. Data were pooled, where possible, and analysed using appropriate statistical methods. 3. Odds ratios or average differences were calculated. 4. Only 'intention to treat' data were included. Where a cross-over design was employed (Devanand, 1998), only the initial phase of the study was used to compare haloperidol versus placebo. 5. Sensitivity analysis was applied to heterogeneity of results and to gauge the effect of the included studies of small sample size. 6. In addition to the overall meta-analysis, individual analyses of the reports were carried out to examine the effect of degree of dementia, dose of haloperidol, and duration of therapy on agitated dementia. Analysis included the following groups: All patients treated with haloperidol compared with placebo. MAIN RESULTS: There were five included trials. All studies stated "intention to treat" analysis of their results. Three studies were from the United States, and two studies were from Europe. Two studies examined patients with various forms of dementia, and three studies included only patients with diagnosed Alzheimer's dementia. 1. Overall meta-analysis of the response of agitated patients to haloperidol, compared with controls, showed no improvement in agitation. There is some evidence that haloperidol helps to control aggression. Adverse reactions and dropouts were more frequent among haloperidol treated patients, compared with controls. This meta-analysis provided no information about the relationship between the degree of dementia, the kind of agitation manifested, or the dosage and duration of therapy with haloperidol and response to treatment of demented patients with agitation. 2. The results of this meta-analysis were too broad to permit specific recommendations for treatment of agitated dementia with haloperidol. 3. Higher dose haloperidol, or prolonged haloperidol (12 weeks compared with 3 - 6 weeks) was associated with increased side effects, largely related to Parkinsonian symptoms of rigidity and bradykinesia. REVIEWER'S CONCLUSIONS: 1. Haloperidol appeared to provide no improvement in agitation among demented patients compared with placebo, but side effects were frequent. 2. Dropout rates were higher for haloperidol compared with placebo treated patients, suggesting that side effects led to discontinuation of treatment in some patients. 3. Because of the wide focus of this meta-analysis, not enough information was provided to permit recommendations linking haloperidol treatment of agitated dementia to degree of dementia, manifestations of agitation, or dosage and duration of treatment of haloperidol. 4. Individual analysis of reports indicated that higher dose haloperidol (more than 2 mg per day) may have been more effective than lower dose haloperidol (less than 2 mg per day) in controlling aggression, but not other manifestations of agitation, among patients with mild to moderate dementia. 5. Similar analysis suggested that prolonged therapy with haloperidol (more than 3 - 6 wks) or higher dosage (more than 2 mg per day) was more likely to result in side effects than were short term therapy (3 weeks) or lower dose haloperidol (less than 2 mg per day). 6. The reports provided too little information to permit interpretation of the effect of degree or type of dementia on response to haloperidol. Except for a favorable response of aggression to haloperidol, no other manifestations of agitated dementia were found to have improved following therapy with haloperidol, compared with controls.

Aggression↗

PubMed2006

Accuracy of B-type natriuretic peptide tests to exclude congestive heart failure: systematic review of test accuracy studies.

BACKGROUND: Congestive heart failure (CHF) is a major public health problem. The use of B-type natriuretic peptide (BNP) tests shows promising diagnostic accuracy. Herein, we summarize the evidence on the accuracy of BNP tests in the diagnosis of CHF and compare the performance of rapid enzyme-linked immunosorbent assay (ELISA) and standard radioimmunosorbent assay (RIA) tests. METHODS: We searched electronic databases and the reference lists of included studies, and we contacted experts. Data were extracted on the study population, the type of test used, and methods. Receiver operating characteristic (ROC) plots and summary ROC curves were produced and negative likelihood ratios pooled. Random-effect meta-analysis and metaregression were used to combine data and explore sources of between-study heterogeneity. RESULTS: Nineteen studies describing 22 patient populations (9 ELISA and 13 RIA) and 9093 patients were included. The diagnosis of CHF was verified by echocardiography, radionuclide scan, or echocardiography combined with clinical criteria. The pooled negative likelihood ratio overall from random-effect meta-analysis was 0.18 (95% confidence interval [CI], 0.13-0.23). It was lower for the ELISA test (0.12; 95% CI, 0.09-0.16) than for the RIA test (0.23; 95% CI, 0.16-0.32). For a pretest probability of 20%, which is typical for patients with suspected CHF in primary care, a negative result of the ELISA test would produce a posttest probability of 2.9%; a negative RIA test, a posttest probability of 5.4%. CONCLUSIONS: The use of BNP tests to rule out CHF in primary care settings could reduce demand for echocardiography. The advantages of rapid ELISA tests need to be balanced against their higher cost.

Biomarkers↗

PubMed2006

Clinical and demographic predictors of long-term disability in patients with relapsing-remitting multiple sclerosis: a systematic review.

OBJECTIVE: To identify clinical and demographic factors associated with long-term disability in patients with relapsing-remitting multiple sclerosis. DATA SOURCES: We searched the MEDLINE (1966-May 2005), EMBASE, CINAHL, Cochrane, and PsycINFO computerized databases, and reviewed reference lists of retrieved articles. STUDY SELECTION: We included studies that examined predictors of long-term disability in patients with relapsing-remitting multiple sclerosis. We excluded studies that did not distinguish relapsing-remitting multiple sclerosis from primary progressive multiple sclerosis, enrolled fewer than 40 subjects, observed subjects for less than 5 years, or collected follow-up information in less than 80% of the inception cohort. DATA EXTRACTION: Two reviewers assessed study quality in 4 domains: cohort assembly, definitions and assessments of prognostic factors and outcomes, and statistical methods. One reviewer extracted data on the direction, magnitude, precision, and statistical significance of the effect of each predictor on prognosis. DATA SYNTHESIS: Heterogeneity of study designs precluded us from pooling the results of 27 eligible studies. Study quality was limited by cross-sectional design, enrollment of prevalent cases from referral centers, and lack of multivariate adjustment. Sphincter symptoms at onset (hazard ratio, 1.1-3.1), incomplete recovery from the first attack (hazard ratio, 1.3-3.3), and a short interval between the first and second attack (hazard ratio, 1.6-1.9) were most strongly and consistently associated with poor prognosis. Other factors widely believed to be of prognostic importance, including sex and age at onset, demonstrated inconsistent or weak effects on prognosis. CONCLUSIONS: The most robust predictors of long-term physical disability in relapsing-remitting multiple sclerosis are sphincter symptoms at onset and early disease course outcomes. These factors can be used to guide treatment decisions for drugs with significant toxicities.

Adult↗

PubMed2005

Translational research on the way to effective therapy for Alzheimer disease.

CONTEXT: Alzheimer disease (AD) is a major public health issue with a prediction of 12 million Americans being affected by 2025 from the present 4 million. Molecular and genetic findings have provided significant insights into the roles that amyloid, tau, and apolipoprotein E isoforms have in the causation of AD. A central issue in AD pathogenesis is the amyloid cascade hypothesis. It states that abnormal amyloid processing and accumulation is the primary causative factor of AD and other associated neuropathologic abnormalities are of secondary consequence. It is presented to provide the rationale for novel drug and vaccination therapeutic strategies. Future research directed at prediction and prevention of AD through a genomic and proteomic analysis with identification of multiple polymorphic genes that interact, resulting in increased risk for late-onset AD, are the realistic and ultimate goals. A new approach for drug development is required, one that will emphasize a genomic and proteomic analysis to identify at-risk gene sets whose genetic expression is sufficient to cause late onset, sporadic AD. Prediction and prevention of disease prior to clinical signs and symptoms are the goals. OBJECTIVE: A review and analysis from electronic literature databases and subsequent reference searches of the molecular genetic data. including pertinent genetic mutations and abnormal biochemical findings causal of AD, are cited. The amyloid cascade hypothesis, the contributions of apolipoprotein E, and hyperphosphorylated tau are discussed as to their roles in pathogenesis. Molecular targets for potential drug and vaccination therapies are cited from a critical assessment of the molecular and biomedical data. These data form the basis for rational, target-specific drug and vaccination therapies currently employed and planned for the near future. Phase 2 and 3 clinical trial results of drug and vaccination therapies are cited. CONCLUSIONS: A new approach is needed as current pharmacologic therapy directed at symptomatic relief has proved to be marginally effective. The genomic and proteomic basis of AD will be defined in the near future, and corresponding molecular therapeutic targets will be identified. Genomic neurology has arrived and its application to resolving AD is our best hope.

Alzheimer Disease↗

PubMed2004

Bariatric surgery: a systematic review and meta-analysis.

CONTEXT: About 5% of the US population is morbidly obese. This disease remains largely refractory to diet and drug therapy, but generally responds well to bariatric surgery. OBJECTIVE: To determine the impact of bariatric surgery on weight loss, operative mortality outcome, and 4 obesity comorbidities (diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea). DATA SOURCES AND STUDY SELECTION: Electronic literature search of MEDLINE, Current Contents, and the Cochrane Library databases plus manual reference checks of all articles on bariatric surgery published in the English language between 1990 and 2003. Two levels of screening were used on 2738 citations. DATA EXTRACTION: A total of 136 fully extracted studies, which included 91 overlapping patient populations (kin studies), were included for a total of 22,094 patients. Nineteen percent of the patients were men and 72.6% were women, with a mean age of 39 years (range, 16-64 years). Sex was not reported for 1537 patients (8%). The baseline mean body mass index for 16 944 patients was 46.9 (range, 32.3-68.8). DATA SYNTHESIS: A random effects model was used in the meta-analysis. The mean (95% confidence interval) percentage of excess weight loss was 61.2% (58.1%-64.4%) for all patients; 47.5% (40.7%-54.2%) for patients who underwent gastric banding; 61.6% (56.7%-66.5%), gastric bypass; 68.2% (61.5%-74.8%), gastroplasty; and 70.1% (66.3%-73.9%), biliopancreatic diversion or duodenal switch. Operative mortality (< or =30 days) in the extracted studies was 0.1% for the purely restrictive procedures, 0.5% for gastric bypass, and 1.1% for biliopancreatic diversion or duodenal switch. Diabetes was completely resolved in 76.8% of patients and resolved or improved in 86.0%. Hyperlipidemia improved in 70% or more of patients. Hypertension was resolved in 61.7% of patients and resolved or improved in 78.5%. Obstructive sleep apnea was resolved in 85.7% of patients and was resolved or improved in 83.6% of patients. CONCLUSIONS: Effective weight loss was achieved in morbidly obese patients after undergoing bariatric surgery. A substantial majority of patients with diabetes, hyperlipidemia, hypertension, and obstructive sleep apnea experienced complete resolution or improvement.

Adolescent↗

PubMed2005

Effects of computerized clinical decision support systems on practitioner performance and patient outcomes: a systematic review.

CONTEXT: Developers of health care software have attributed improvements in patient care to these applications. As with any health care intervention, such claims require confirmation in clinical trials. OBJECTIVES: To review controlled trials assessing the effects of computerized clinical decision support systems (CDSSs) and to identify study characteristics predicting benefit. DATA SOURCES: We updated our earlier reviews by searching the MEDLINE, EMBASE, Cochrane Library, Inspec, and ISI databases and consulting reference lists through September 2004. Authors of 64 primary studies confirmed data or provided additional information. STUDY SELECTION: We included randomized and nonrandomized controlled trials that evaluated the effect of a CDSS compared with care provided without a CDSS on practitioner performance or patient outcomes. DATA EXTRACTION: Teams of 2 reviewers independently abstracted data on methods, setting, CDSS and patient characteristics, and outcomes. DATA SYNTHESIS: One hundred studies met our inclusion criteria. The number and methodologic quality of studies improved over time. The CDSS improved practitioner performance in 62 (64%) of the 97 studies assessing this outcome, including 4 (40%) of 10 diagnostic systems, 16 (76%) of 21 reminder systems, 23 (62%) of 37 disease management systems, and 19 (66%) of 29 drug-dosing or prescribing systems. Fifty-two trials assessed 1 or more patient outcomes, of which 7 trials (13%) reported improvements. Improved practitioner performance was associated with CDSSs that automatically prompted users compared with requiring users to activate the system (success in 73% of trials vs 47%; P = .02) and studies in which the authors also developed the CDSS software compared with studies in which the authors were not the developers (74% success vs 28%; respectively, P = .001). CONCLUSIONS: Many CDSSs improve practitioner performance. To date, the effects on patient outcomes remain understudied and, when studied, inconsistent.

Clinical Pharmacy Information Systems↗

PubMed2026

Management of Soft Tissue and Visceral Leiomyosarcomas.

IMPORTANCE: Leiomyosarcoma is a rare and heterogeneous malignant mesenchymal neoplasm associated with substantial morbidity and mortality. Given recent advances in biologic understanding and the complexity of leiomyosarcoma, a consensus-driven approach is needed to harmonize management and address remaining clinical and research gaps. OBJECTIVE: To provide an evidence-based synthesis of current diagnostic and therapeutic approaches for leiomyosarcoma by an international panel of physicians, researchers, and patient advocates, focusing on site-specific management, systemic therapy strategies, and key areas of clinical uncertainty, while identifying unmet needs and research priorities. EVIDENCE REVIEW: This review is based on a comprehensive evaluation of the literature, including clinical trials, observational studies, and international consensus guidelines. Sources were identified through MEDLINE (via PubMed) and Embase database searches and reference screening, then supplemented by multidisciplinary expert consensus. Emphasis was placed on studies informing diagnosis, surgical management, radiotherapy, and systemic therapy in leiomyosarcoma. FINDINGS: The rarity and heterogeneity of leiomyosarcoma poses substantial challenges in its management. In localized disease, complete surgical resection remains the cornerstone of treatment, with evidence supporting the use of site-specific perioperative treatment strategies. Prospective data supporting neoadjuvant or adjuvant chemotherapy are lacking, and the role of radiotherapy differs across anatomic disease sites and institutions. In advanced disease, multiple systemic therapies demonstrate activity, including anthracycline-based and gemcitabine-based combinations, trabectedin, and tyrosine kinase inhibitors, although optimal sequencing after first-line therapy remains undefined. Emerging data suggest potential benefit from treatment continuation strategies and selected use of local therapies in oligometastatic settings. Molecular heterogeneity is increasingly recognized but has not yet translated into routine clinical implementation, and integration of molecular profiling into diagnostic pathways for predictive and therapeutic insights remains an unmet need. CONCLUSIONS AND RELEVANCE: This international consensus addresses the diagnosis and management of leiomyosarcoma. Management requires a multidisciplinary, site-specific approach informed by limited but evolving evidence. Key uncertainties persist, particularly regarding perioperative therapy, optimal sequencing and combination of systemic treatments, and integration of molecular data. Continued international collaboration and leiomyosarcoma-specific clinical trials are needed to refine treatment strategies and improve patient outcomes.

Journal Article↗

PubMed2000

Serum protein immunogenicity: implications for liver xenografting.

The objectives of this study were threefold: (i) assess immunogenicity of donor plasma proteins following hepatic xenotransplantation, (ii) identify potential immunogens, and (iii) consider the implications of antibody formation against these plasma proteins in xenograft survival. We studied liver and heart xenografts in a concordant combination, hamster to rat. All grafts were examined at necropsy for evidence of rat immunoglobulin G (IgG) deposition. Cardiac xenografts were placed in recipients who had, or had not, been sensitized with hamster serum. Hepatic xenografts were placed in naive recipients to see if antibodies to hamster serum proteins could be eluted from the rejecting organ. Sera of immunized rats were examined for the presence of anti-hamster antibodies by immunoelectrophoresis and by Western blotting following sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) separation of hamster serum. Antibodies in sera of immunized rats were compared with those eluted from rejecting livers. Candidate antigens were identified by tandem mass spectrometry, sequence analysis, and reference to protein databases. Results showed that sera of immunized rats recognized a minimum of four different antigens in hamster serum by immunoelectrophoresis, and a minimum of seven by the more sensitive SDS-PAGE Western blot. IgG eluted from rejecting livers bound three of seven candidate antigens recognized by sera of the immunized animals. Sequence analysis searches revealed proteinase inhibitors in each of the three SDS-PAGE bands common to the above samples. All of these candidate proteinase inhibitor immunogens share a common catabolic fate, uptake via the lipoprotein-related protein (LRP/alpha 2-macroglobulin receptor (CD91). Sensitization to hamster serum proteins hastened cardiac xenograft rejection in 30-50% of recipients (depending on sensitization protocol). Vascular deposition of rat IgG occurred in all rejecting xenografts. Antibody binding to proteinase inhibitors could disturb their functional activity and contribute to the pathogenesis of delayed xenograft rejection.

Amino Acid Sequence↗

PubMed2001

Anorexia nervosa and social class.

OBJECTIVES: (1) To examine social class status of female patients with anorexia nervosa presenting over a 33-year period; (2) to identify any differences in clinical features between the social classes. METHOD: Retrospective survey using comprehensive clinical database of patients referred to a national specialist center for the assessment and treatment of anorexia nervosa. Social class was defined using UK Registrar General's classification of father's occupation. Statistical methods included initial univariate analyses and subsequent ordinal logistic regression. RESULTS: (1) Social class distribution was consistently weighted toward social classes 1/2. (2) Possible clinical indicators examined included low body weight, binge eating, and consequent weight-regulatory behaviors such as vomiting and laxative and diuretic misuse. These clinical features and their distribution proved to be similar across the social groups. Clinically rated quality of family relationships and types of family constellations were also consistent across the social classes. (3) Dieting prodromata and onset of the disorder occurred at younger ages in social classes 1/2. (4) A modest shift in social class distribution over time was apparent, with slightly more patients presenting post-1985 likely to come from lower social classes. Claims that the social class distribution is a product of referral patterns and acceptances are disputed. CONCLUSION: We suggest that the social class bias reflects a sociocultural influence; a product of the disorder significantly often arising as an avoidant response to the conflict between social class-related family values/attitudes and adolescent turbulence within that family.

Adult↗

PubMed2000

Pharmacotherapy for hypertension in the elderly.

OBJECTIVES: To quantify the long-term effects of antihypertensive drug therapy on morbidity and mortality in the elderly. To characterize co morbid risk profiles of trial participants. SEARCH STRATEGY: Electronic search of WHO-ISH Collaboration register (August 1997), The Cochrane Library (1997; Issue 1), MEDLINE (1966 to April 1997) and two Japanese databases (1973-1995); references from reviews, trials and 10 previously published meta-analyses; and experts. SELECTION CRITERIA: Randomized controlled trials of at least one year duration in hypertensive elders (at least 60 years old) assessing antihypertensive drug therapy and providing morbidity and mortality data. DATA COLLECTION AND ANALYSIS: At least two independent reviewers abstracted data on morbidity and mortality results and trial characteristics. The following outcomes were assessed: total mortality; coronary heart disease (CHD) mortality; combined CHD morbidity and mortality; cerebrovascular mortality; combined cerebrovascular morbidity and mortality; cardiovascular mortality; combined cardiovascular morbidity and mortality; and drop outs due to side effects of treatment. MAIN RESULTS: Fifteen trials including 21,908 elderly subjects were identified. The average prevalence of cardiovascular risk factors, cardiovascular disease, and competing co morbid diseases was lower among trial participants than the general population of hypertensive elderly persons. Most subjects were 60 to 80 years old. Most trials were conducted in Western, industrialized countries and evaluated diuretic and beta-blocker therapies. Event rates per 1000 participants over approximately 5 years indicated that antihypertensive drug therapy was beneficial. Cardiovascular morbidity and mortality was reduced from 177 to 126 events (95% CI of the difference 31 to 73). Cardiovascular mortality was reduced from 69 to 50 deaths (95% CI of the difference 9 to 31). Total mortality was reduced from 129 to 111 deaths (95% CI of difference 4 to 28). The data from the three trials restricted to persons with isolated systolic hypertension indicated a significant benefit: cardiovascular morbidity and mortality over approximately 5 years was reduced from 157 to 104 events per 1000 participants (95% CI of the difference 12 to 89). Numbers of participants who dropped out of trials secondary to adverse drug effects were often not reported. The four trials that did report this data showed a wide variation in drop out rates ranging from no significant differences between treatment and control groups to as many as one out of four patients dropping out due to side effects of treatment. REVIEWER'S CONCLUSIONS: Randomized controlled trials establish that treating healthy older persons with hypertension is highly efficacious. Benefits of treatment with low dose diuretics or beta-blockers are clear for persons in their 60s to 70s with either diastolic or systolic hypertension. Differential treatment effects based on patient risk factors, pre-existing cardiovascular disease and competing co-morbidities could not be established from the published trial data.

Aged↗

PubMed2000

Corticosteroids for the resolution of malignant bowel obstruction in advanced gynaecological and gastrointestinal cancer.

BACKGROUND: Gastrointestinal and ovarian cancers are common cancers. The incidence of associated malignant bowel obstruction in patients with advanced cancers of these types is not known, and the best management of these patients is controversial. Inappropriate management may result in uncontrolled (faeculant) vomiting, pain and distress. Management of the symptoms can include palliative surgery, nasogastric tube suction together with intravenous fluids, or pharmacological means, such as corticosteroids. There is uncertainty regarding both the efficacy and possible harmful effects of corticosteroids, and also the most effective type, dose/dosing regime, route and period of administration. OBJECTIVES: To locate, appraise and summarise evidence from scientific studies on intestinal obstruction due to advanced gynaecological and gastrointestinal cancer, in order to assess the efficacy of corticosteroids. SEARCH STRATEGY: A comprehensive list of all studies was provided by an extensive search of the electronic databases, relevant journals, reference lists, the grey literature, contact with investigators and other search strategies outlined in the methods. SELECTION CRITERIA: As the review concentrates on the 'best evidence' available of the role of corticosteroids in malignant bowel obstruction due to advanced gynaecological and gastrointestinal cancer the inclusion criteria were kept fairly broad so as to include all studies relevant to the question DATA COLLECTION AND ANALYSIS: Data extraction forms were used to collect data from the studies included in the review. The data was checked by a secondary searcher to reduce error. A qualitative analysis was performed of the dichotomous data of resolution of obstruction and death at one month, obtained from the randomised controlled trials of corticosteroids versus placebo. Both fixed and random effect models were used. Number needed to treat (NNT) was derived from the odds ratio. Kaplan-Meier survival curves from individual patient data were also analysed. Studies of lower methodological quality were assessed in a qualitative manner. MAIN RESULTS: Three unpublished, randomised, placebo, double blind controlled trials and seven published (prospective and retrospective) trials were considered eligible. Using only the randomised trials, there is a trend, which is not statistically significant, for the resolution of bowel obstruction using corticosteroids. There is no statistically significant difference in mortality at one month, nor in the Kaplan-Meier curves, which describe the survival of patients on corticosteroids or placebo. Number needed to treat is 6 (3, infinity) ie six patients need to be treated with corticosteroids to resolve one episode of bowel obstruction. The results are robust to fixed and random effects models and to 'best' and 'worst case' scenarios on the missing data from patients. The morbidity associated with corticosteroids appears to be very low, though the quality of the data limits this conclusion. No other outcomes were available from the published data or from the authors. REVIEWER'S CONCLUSIONS: There is a trend for evidence that corticosteroids of dose range 6-16 mg dexamethasone given intravenously may bring about the resolution of bowel obstruction. Equally, the incidence of side effects in all the included studies is extremely low. Corticosteroids do not seem to affect the length of survival of these patients.

Female↗