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Biomedical subjects

B Pham

Publications and source records attributed to B Pham.

At least 37 records · Page 2Linked to original sources
PubMed2000

Pharmacological management of intermittent claudication: a meta-analysis of randomised trials.

Intermittent claudication, a symptom of atherosclerosis in the large vessels of the lower limbs, greatly affects patient mobility and quality of life. Medical therapy for a moderate form of this condition includes vasodilators, antiplatelet agents and alternative treatments such as ginkgo biloba.A meta-analysis of results from 52 trials (including 5088 patients) was conducted for all current medical therapies for intermittent claudication. After 24 weeks, some of the medical therapies were found to be more effective than placebo for the primary end-points of either pain-free walking distance or maximum walking distance. Vasodilators presented the best results in walking distance. Pentoxifylline offered better results than naftidrofuryl, although the treatment benefit, measured in additional metres walked with treatment than without, was modest. Antiplatelets, ginkgo biloba and levocarnitine were slightly more effective than placebo, although the treatment benefit was of limited clinical importance. On average, patients walked 60m further with therapy than without, and only about half of that added distance was pain-free. Very little consistent information was available for other clinical end-points, such as overall mortality and adverse effects. These data suggest that some of the medical therapy, pentoxifylline in particular, can only modestly increase functional status in patients with moderate intermittent claudication. There is a need for uniformity in research design and reporting of trials. A future trial comparing medical therapy with physical therapy is indicated.

Humans↗
PubMed2000

Hemiparetic cerebral palsy: clinical pattern and imaging in prediction of outcome.

BACKGROUND: Hemiparetic cerebral palsy (HCP) is described as having two main forms: arm-dominant, associated with large cortical/subcortical lesions; leg-dominant, associated with lesions of central white matter. Epilepsy and cognitive deficits are common in the former pattern and rare in the latter. Some authors have recommended routine imaging studies in children with HCP as an assessment of etiology and a predictor of outcome. The present study compares the relative values of clinical analysis and imaging in predicting epilepsy and cognitive disabilities. METHODS: Forty-one consecutive patients with HCP underwent careful clinical assessment and imaging studies (primarily computed tomography) and were followed prospectively for the development of recurrent afebrile seizures and academic difficulties. RESULTS: Twenty of the 41 patients (48.8%) were arm-dominant, 14/41 (34.1%) leg-dominant, and 7/41 (17.1%) proportional (arm = leg). The principal imaging findings were: arm-dominant patients - large arterial infarcts, porencephalic cysts, brain malformations; leg-dominant - periventricular leukomalacia; proportional - porencephaly. Arm-dominant hemiparesis and radiologic evidence of cortical pathology were both predictive of cognitive deficits (odds ratios 14.2 [95% CI 2.6, 75.8] and 5.7 [95% CI 1.4. 22.3] respectively). For the development of epilepsy, both evaluation techniques were again predictive, with imaging findings of cortical pathology being particularly powerful (clinical pattern OR 18.0 [95% CI 3.0, 107.7]; imaging OR 80.7 [95% CI 8.5, 767.3]). CONCLUSIONS: In this study, the clinical pattern of HCP and the radiological findings were both predictive of outcome, with absence of cortical pathology on imaging being particularly predictive for the absence of epilepsy. While the clinical pattern, in isolation, appears helpful in predicting outcome, our results suggest that both evaluation tools have important roles to play in the evaluation of HCP patients.

Adult↗
PubMed1999

The effectiveness of glucocorticoids in treating croup: meta-analysis.

OBJECTIVE: To determine the effectiveness of glucocorticoid treatment in children with croup. DESIGN: Meta-analysis of randomised controlled trials that examine the effectiveness of glucocorticoid treatment in children with croup. MAIN OUTCOME MEASURES: Score on scale measuring severity of croup, use of cointerventions (adrenaline (epinephrine), antibiotics, or supplemental glucocorticoids), length of stay in accident and emergency or in hospital, and rate of hospitalisation. RESULTS: Twenty four studies met the inclusion criteria. Glucocorticoid treatment was associated with an improvement in the croup severity score at 6 hours with an effect size of -1.0 (95% confidence interval -1.5 to -0.6) and at 12 hours -1.0 (-1.6 to -0.4); at 24 hours this improvement was no longer significant (-1.0, -2.0 to 0.1). There was a decrease in the number of adrenaline treatments needed in children treated with glucocorticoids: a decrease of 9% (95% confidence interval 2% to 16%) among those treated with budesonide and of 12% (4% to 20%) among those treated with dexamethasone. There was also a decrease in the length of time spent in accident and emergency (-11 hours, 95% confidence interval -18 to 4 hours), and for inpatients hospital stay was reduced by 16 hours (-31 to 1 hour). Publication bias seems to play a part in these results. CONCLUSIONS: Dexamethasone and budesonide are effective in relieving the symptoms of croup as early as 6 hours after treatment. Fewer cointerventions are used and the length of time spent in hospital is decreased in patients treated with glucocorticoids.

Anti-Bacterial Agents↗
PubMed1999

Activation of membrane-associated procaspase-3 is regulated by Bcl-2.

The mechanism by which membrane-bound Bcl-2 inhibits the activation of cytoplasmic procaspases is unknown. Here we characterize an intracellular, membrane-associated form of procaspase-3 whose activation is controlled by Bcl-2. Heavy membranes isolated from control cells contained a spontaneously activatable caspase-3 zymogen. In contrast, in Bcl-2 overexpressing cells, although the caspase-3 zymogen was still associated with heavy membranes, its spontaneous activation was blocked. However, Bcl-2 expression had little effect on the levels of cytoplasmic caspase activity in unstimulated cells. Furthermore, the membrane-associated caspase-3 differed from cytosolic caspase-3 in its responsiveness to activation by exogenous cytochrome c. Our results demonstrate that intracellular membranes can generate active caspase-3 by a Bcl-2-inhibitable mechanism, and that control of caspase activation in membranes is distinct from that observed in the cytoplasm. These data suggest that Bcl-2 may control cytoplasmic events in part by blocking the activation of membrane-associated procaspases.

Apoptosis↗
PubMed1999

A measure of limited joint motion and deformity correlates with HLA-DRB1 and DQB1 alleles in patients with rheumatoid arthritis.

OBJECTIVE: To assess factors associated with a poor outcome in rheumatoid arthritis (RA), a measure was developed of limited joint motion and deformity, a deformity index (DI), and correlated biochemical and genetic variables with the magnitude of the DI. METHODS: Forty patients were evaluated in a cross sectional study. Clinical measures included the DI and Health Assessment Questionnaire, and disease variables included the erythrocyte sedimentation rate, C reactive protein, rheumatoid factor, and HLA-DRB1 and DQB1 alleles. RESULTS: Significant correlations were noted between increasing DI and duration of RA and concentration of C reactive protein. Patients with a DQB1*301 allele or DR4 allele had a higher DI than those without, and a positive trend was noted between increasing DI and dose of DRB1 RA susceptibility alleles. The trend was lost when a non-linear regression technique was used to remove the effect attributable to C reactive protein, suggesting an interrelation between persistent inflammation and genetics in determining total joint damage. CONCLUSIONS: The DI may be useful to study interactions between genetic and inflammatory processes in rheumatoid disease progression.

Adult↗
PubMed1999

Meta-analysis: an adolescent in need of evidence and a watchful eye.

Meta-analysis is a relatively new development in medicine. It is conceptually appealing, summarizing the medical literature in a rigorous manner and providing clinicians with a global picture regarding the merits of interventions. This process can help clinicians choose appropriate, evidence-based management options for their patients. The early enthusiasm for this approach has more recently been called into question. The reliability, and therefore the usefulness, of meta-analysis will improve as more evidence concerning the rigorous ways to conduct and report such studies is developed.

Cost-Benefit Analysis↗
PubMed1999

Validity of area-under-the-curve analysis to summarize effect in rheumatoid arthritis clinical trials.

There is a continuing interest in increasing the statistical efficiency of the analysis of clinically meaningful endpoints in rheumatology. One issue that is attracting increasing attention is whether the conventional practice of only reporting the outcome at the end of the study (EOS) might be replaced or complemented by a longitudinal summary that better reflects the clinical course of the disease. The area under the curve (AUC) is a summary measure that integrates serial assessments of a patient's endpoint over the duration of the study. We evaluated the utility of AUC as a summary measure for the analysis and reporting of two RA trials: (i) methotrexate combined with cyclosporine versus methotrexate and placebo in partial methotrexate responders in relatively late disease, and (ii) prednisone plus methotrexate plus sulfasalazine versus sulfasalazine alone in relatively early disease. We replicated the published results of each trial first using the conventional EOS and then AUC summaries. For each patient, the changes from baseline over time were transformed into a summary measure by calculating AUC using the trapezium rule and then standardizing it by the study duration. Using an approach similar to the index of responsiveness to change, we scaled treatment differences derived from EOS and AUC summary measures by their standard deviation of the control group. This signal-versus-noise ratio captures the treatment discrimination ability of each summary measure. Compared to EOS and within each treatment group, the AUC summary reported smaller effects (i.e., change from baseline) with reduced errors in the estimates. AUC measures preserved discriminant validity in treatment comparisons and reported smaller but more precise treatment effect estimates. In the COBRA trial with rapidly-acting medications, AUC seemed to be more sensitive than EOS to detect treatment difference. With slow acting medications and in relatively late disease patients as in the cyclosporine trial, EOS was more sensitive to detect treatment difference than was AUC. In this setting, AUC, however, still seemed to be more sensitive than EOS for the two responsive-to-change endpoints: tender joint counts and pain by visual analog scale. AUC integrates repeated assessments during the trial duration into summary measures. Compared to EOS, the report of RA trial results using AUC summary provides smaller estimates of treatment effects but with better precision. AUC summary is likely to preserve treatment group discrimination taking into account the appropriate onset and offset of the drug action. Trial reports using AUC summary have smaller effect sizes. For trials with long acting medications and short duration similar to the cyclosporine trial, AUC still preserves treatment discrimination but may not be as sensitive as EOS. The calculations of AUC require some additional work in the analysis of each endpoint.

Antirheumatic Agents↗
PubMed1999

A cumulative meta-analysis of the effectiveness of defibrillator-capable emergency medical services for victims of out-of-hospital cardiac arrest.

STUDY OBJECTIVE: More than 1,000 patients experience sudden cardiac arrest each day. Treatment for this includes cardiopulmonary resuscitation (CPR) and emergency medical services (EMS) that provide CPR-basic life support (BLS), BLS with defibrillation (BLS-D), or advanced life support (ALS). Our previous systematic review of treatments for sudden cardiac arrest was limited by suboptimal data. Since then, debate has increased about whether bystander CPR is effective or whether attention should focus instead on rapid defibrillation. Therefore a cumulative meta-analysis was conducted to determine the relative effectiveness of differences in the defibrillation response time interval, proportion of bystander CPR, and type of EMS system on survival after out-of-hospital cardiac arrest. METHODS: A comprehensive literature search was performed by using a priori exclusion criteria. We considered EMS systems that provided BLS-D, ALS, BLS plus ALS, or BLS-D plus ALS care. A generalized linear model was used with dispersion estimation for random effects. RESULTS: Thirty-seven eligible articles described 39 EMS systems and included 33,124 patients. Median survival for all rhythm groups to hospital discharge was 6.4% (interquartile range, 3.7 to 10.3). Odds of survival were 1.06 (95% confidence interval [CI], 1.03 to 1.09; P <.01) per 5% increase in bystander CPR. Survival was constant if the defibrillation response time interval was less than 6 minutes, decreased as the interval increased from 6 to 11 minutes, and leveled off after 11 minutes (P <.01). Compared with BLS-D, odds of survival were as follows: ALS, 1. 71 (95% CI, 1.09 to 2.70; P =.01); BLS plus ALS, 1.47 (95% CI, 0.89 to 2.42; P =.07); and BLS with defibrillation plus ALS, 2.31 (95% CI, 1.47 to 3.62; P <.01.) CONCLUSION: We confirm that greater survival after sudden cardiac arrest is associated with provision of bystander CPR, early defibrillation, or ALS. More research is required to evaluate the relative benefit of early defibrillation versus early ALS.

Electric Countershock↗
PubMed1998

Carotid endarterectomy for asymptomatic carotid stenosis: a meta-analysis.

OBJECTIVE: To assess the value of carotid endarterectomy for prevention of stroke in patients with asymptomatic carotid stenosis. DESIGN: Systematic review and meta-analysis of randomised controlled trials in patients with asymptomatic carotid stenosis in which subjects were allocated to carotid endarterectomy or to medical treatment alone. SUBJECTS: Five trials enrolled 2440 patients with stenosis >/ 50%. MAIN OUTCOME MEASURES: Stroke ipsilateral to the stenosis, all strokes, and perioperative complications (stroke or death). RESULTS: In patients who underwent carotid endarterectomy (n=1215) there was a significant reduction in the odds of ipsilateral stroke plus perioperative stroke or death (odds ratio 0.62; 95% confidence interval 0.44 to 0.86), corresponding to a 2% absolute risk reduction over about 3.1 years. The prevalence of stroke in any location was also reduced (0.68; 0.51 to 0.9) in patients undergoing carotid endarterectomy. During the immediate postoperative period there was an increased prevalence of stroke or death among such patients (4.51; 2.36 to 8.64). CONCLUSION: Carotid endarterectomy in patients with asymptomatic carotid stenosis unequivocally reduces the incidence of ipsilateral stroke, though the absolute benefit is relatively small. Given the modest benefit of surgery for unselected patients with asymptomatic carotid artery stenosis carotid endarterectomy cannot be routinely recommended for these patients pending reliable identification of high risk subgroups, and medical management is a sensible alternative for most patients.

Aged↗
PubMed1998

Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses?

BACKGROUND: Few meta-analyses of randomised trials assess the quality of the studies included. Yet there is increasing evidence that trial quality can affect estimates of intervention efficacy. We investigated whether different methods of quality assessment provide different estimates of intervention efficacy evaluated in randomised controlled trials (RCTs). METHODS: We randomly selected 11 meta-analyses that involved 127 RCTs on the efficacy of interventions used for circulatory and digestive diseases, mental health, and pregnancy and childbirth. We replicated all the meta-analyses using published data from the primary studies. The quality of reporting of all 127 clinical trials was assessed by means of component and scale approaches. To explore the effects of quality on the quantitative results, we examined the effects of different methods of incorporating quality scores (sensitivity analysis and quality weights) on the results of the meta-analyses. FINDINGS: The quality of trials was low. Masked assessments provided significantly higher scores than unmasked assessments (mean 2.74 [SD 1.10] vs 2.55 [1.20]). Low-quality trials (score < or = 2), compared with high-quality trials (score > 2), were associated with an increased estimate of benefit of 34% (ratio of odds ratios [ROR] 0.66 [95% CI 0.52-0.83]). Trials that used inadequate allocation concealment, compared with those that used adequate methods, were also associated with an increased estimate of benefit (37%; ROR=0.63 [0.45-0.88]). The average treatment benefit was 39% (odds ratio [OR] 0.61 [0.57-0.65]) for all trials, 52% (OR 0.48 [0.43-0.54]) for low-quality trials, and 29% (OR 0.71 [0.65-0.77]) for high-quality trials. Use of all the trial scores as quality weights reduced the effects to 35% (OR 0.65 [0.59-0.71]) and resulted in the least statistical heterogeneity. INTERPRETATION: Studies of low methodological quality in which the estimate of quality is incorporated into the meta-analyses can alter the interpretation of the benefit of intervention, whether a scale or component approach is used in the assessment of trial quality.

Bias↗
PubMed1998

Influence of arrhythmias on accuracy of non-invasive blood pressure monitors.

PURPOSE: To compare the accuracy of non-invasive blood pressure (NIBP) monitors in response to common cardiac arrhythmias. METHODS: Simulated signals of normal sinus rhythm (NSR), premature ventricular contractions (PVCs), atrial fibrillation (AF) and missed beats (MB) were generated from a Cufflink (Dynatech Nevada) NIBP simulator. Using these signals, the Critikon 1846SX (C1846), Critikon 845xt (C845). Critikon Vital Signs (CVIT), and Hewlett Packard M1008a (HP1008) were studied at a standard dynamic blood pressure of 120/90/80 mmHg, in order to compare monitor accuracy and signal response times. RESULTS: The C845 monitors most closely estimated a simulated SBP of 120 mmHg, although SBP was greater during PVCs and AF than NSR (P < 0.05). The Critikon 1846, Critikon Vital Signs, and Hewlett Packard systematically underestimated SBP during these arrhythmias, but variability was modest, as reflected by small coefficients of variation (< 2% for SBP) with all monitor types. In general, MAP and DBP were less sensitive to the effects of these arrhythmias. Finally, missed beats prolonged signal response times with all four monitor types (P < 0.05), whereas PVCs and AF did not alter this parameter. CONCLUSIONS: This study demonstrates the extent to which the accuracy of NIBP monitors is altered by common cardiac arrhythmias. Differences in the electromechanical characteristics of these devices may help to explain the observed similarities and discrepancies.

Arrhythmias, Cardiac↗
PubMed1998

Management of steroid-dependent asthma with methotrexate: a meta-analysis of randomized clinical trials.

Our objective was to determine whether methotrexate is an effective steroid-sparing agent for patients with severe asthma. Published reports of controlled trials assessing the use of methotrexate in asthma were identified by a search of the MEDLINE, EMBASE, CINAHL, Biological Abstracts on CD, and Current Contents databases. Bibliographies from identified studies and from review articles were manually searched. Published and unpublished reports in any language were identified and assessed for inclusion in the meta-analysis. We selected randomized, double-blind, placebo-controlled trials in which low-dose methotrexate was administered to corticosteroid-dependent asthmatics, and oral steroids were subsequently tapered according to the patients' clinical status. Data were extracted independently by two reviewers. For all eligible trials, the mean reduction in oral corticosteroid dose, the mean change in FEV1, and the standard deviations, were calculated for the treatment and control groups. Data concerning side-effects of therapy were also extracted. Data from 12 studies, reporting on a total of 250 patients, were pooled using a weighted average method, with weights proportional to the inverse of the variance of the treatment effect. Compared to placebo, the use of methotrexate was associated with a pooled 6.0% improvement in FEV1 (95% CI, 1.0-11%) and an 18.2% reduction in oral steroid use (95% CI, 11.7-24.7%). This corresponded to a 3.3 mg day-1 greater reduction in oral steroid use for patients taking methotrexate than for those taking placebo (95% CI, 2.1-4.4 mg day-1). Gastrointestinal complications and transient increases in liver enzymes were more common in patients randomized to methotrexate. Three potentially life-threatening side-effects (two pneumonias and one liver dysfunction) occurred in 159 patients randomized to methotrexate vs. none in those patients on placebo. It was concluded that methotrexate allowed a modest reduction in oral corticosteroid compared to patients receiving placebo. The benefit is relatively small, however, and should be balanced against the potential for side-effects associated with the use of methotrexate.

Asthma↗
PubMed1998

Improvement in cell-mediated immune function during potent anti-human immunodeficiency virus therapy with ritonavir plus saquinavir.

Inhibiting human immunodeficiency virus (HIV) replication with potent antiretroviral therapy may result in improved immune function, and this may lead to favorable outcomes, independent of changes in CD4+ lymphocyte count. The effect of combination protease inhibitor therapy (ritonavir plus saquinavir) on functional measures of cell-mediated immunity in 41 HIV-infected patients from one center of a multicenter trial was investigated. After 24 weeks, median plasma virus load decreased from 4.74 log10 copies/mL to below the detection limit of the assay (2.30 log10), and mean CD4+ lymphocyte count increased from 284 cells/microL to 413 cells/microL. Proliferative responses to phytohemagglutinin developed in 21 of 34 patients in whom responses were absent at baseline. Increases were observed in interleukin-2, -12, and -10 production and in the expression of CD28 on CD8+ lymphocytes. Initiation of potent anti-HIV therapy results in a degree of immune restoration, suggesting that HIV-induced immune suppression is a dynamic and potentially reversible process.

CD28 Antigens↗
PubMed1998

Transfusion and recombinant human erythropoietin requirements differ between dialysis modalities.

BACKGROUND: Before the routine use of recombinant human erythropoietin (rHuEpo), patients dialysed by peritoneal dialysis (PD) received fewer blood transfusions than patients on haemodialysis (HD). We compared transfusion practices in these groups now that the use of rHuEpo has become standard, while controlling for variables known to influence anaemia of end-stage renal disease (ESRD). Maintenance rHuEpo doses were also compared. METHODS: Data were examined for 157 HD and 126 PD patients during a 2-year period. Potential confounders included age, gender, albumin, iron deficiency, parathyroid hormone (PTH), underlying renal disease, comorbid illness, renal transplant, dialysis adequacy and duration. An intent-to-treat analysis was used, with sensitivity analyses to account for change in treatment and transplant. RESULTS: Mean haemoglobin (Hb) was not different (10.47 g/dl for HD, 10.71 g/dl for PD; P = 0.45). Mean monthly transfusion rate was higher for HD (0.47 units per month vs 0.19; P < 0.01). More HD patients received at least one transfusion (52.9 vs 40.9%; P < 0.01). The maintenance rHuEpo dose was higher for HD (7370 U/week vs 5790 U/week; P = 0.01). The only factors associated with risk of being transfused were dialysis duration and mode of dialysis (less risk for PD, odds-ratio 0.57; 95% confidence interval 0.35-0.92). CONCLUSIONS: Despite the routine use of rHuEpo, HD patients received more blood and rHuEpo than PD patients to achieve the same Hb. No patient factors were identified to account for this difference. The use of fewer transfusions and less rHuEpo in PD represents an advantage over HD in terms of both cost and safety.

Anemia↗
PubMed1998

Structural disorders at the insertion of the supraspinatus tendon. Relation to tensile strength.

We examined macroscopically and microscopically 55 cadaver rotator-cuff tendons attached to their humeral heads to determine the distance between the edge of the articular cartilage and the tendon insertion of the supraspinatus (the width of the sulcus) and the score of regressive changes at the sulcus. In 33 specimens we measured the tensile strength. The width of the sulcus was correlated with the score of regressive changes and with the ultimate tensile strength of the supraspinatus tendon. The width of the sulcus correlated positively with the score of regressive changes (r = 0.66, p < 0.0001), but there was a negative correlation between the latter and the ultimate tensile strength (r = -0.81, p = 0.001) and between the width of the sulcus and the ultimate tensile strength (r = -0.74, p = 0.004). We believe that the width of the sulcus is a simple and useful clinical indicator of the integrity and the tensile strength of the supraspinatus tendon.

Adult↗