Systematic review of CT and MR perfusion imaging for assessment of acute cerebrovascular disease.

BACKGROUND AND PURPOSE: Perfusion imaging sequences are an important part of imaging studies designed to provide information to guide therapy for treatment of cerebrovascular disease. The purpose of this study was to perform a meta-analysis of the medical literature on perfusion imaging to determine its role in clinical decision making for patients with acute cerebral ischemia. MATERIALS AND METHODS: We searched MEDLINE by using a strategy that combined terms related to perfusion imaging with terms related to acute cerebral ischemia and brain tumors. We identified 658 perfusion imaging articles and classified them according to the clinical usefulness criteria of Thornbury and Fryback. We found 59 articles with promise of indicating usefulness in clinical decision making. We devised and implemented a clinical decision making scoring scale more appropriate to the topic of acute cerebral ischemia. RESULTS: Several articles provided important insights into the physiologic processes underlying acute cerebral ischemia by correlation of initial perfusion imaging deficits with clinical outcome or ultimate size of the infarct. However, most articles showed relatively low relevance to influencing decisions in implementing treatment. CONCLUSION: Most perfusion imaging articles are oriented toward important topics such as optimization of imaging parameters, determination of ischemia penumbra, and prediction of outcome. However, information as to the role of perfusion imaging in clinical decision making is lacking. Studies are needed to demonstrate that use of perfusion imaging changes outcome of patients with acute cerebral ischemia.

Oxygen for relief of dyspnoea in mildly- or non-hypoxaemic patients with cancer: a systematic review and meta-analysis.

The aim of this study was to determine the efficacy of palliative oxygen for relief of dyspnoea in cancer patients. MEDLINE and EMBASE were searched for randomised controlled trials, comparing oxygen and medical air in cancer patients not qualifying for home oxygen therapy. Abstracts were reviewed and studies were selected using Cochrane methodology. The included studies provided oxygen at rest or during a 6-min walk. The primary outcome was dyspnoea. Standardised mean differences (SMDs) were used to combine scores. Five studies were identified; one was excluded from meta-analysis due to data presentation. Individual patient data were obtained from the authors of the three of the four remaining studies (one each from England, Australia, and the United States). A total of 134 patients were included in the meta-analysis. Oxygen failed to improve dyspnoea in mildly- or non-hypoxaemic cancer patients (SMD=-0.09, 95% confidence interval -0.22 to 0.04; P=0.16). Results were stable to a sensitivity analysis, excluding studies requiring the use of imputed quantities. In this small meta-analysis, oxygen did not provide symptomatic benefit for cancer patients with refractory dyspnoea, who would not normally qualify for home oxygen therapy. Further study of the use of oxygen in this population is warranted given its widespread use.

Cost of multiple sclerosis by level of disability: a review of literature.

We performed a review of the economic literature to identify what is known about the relationship between Expanded Disability Status Scale (EDSS) categories and cost of multiple sclerosis (MS). We sought cohort studies of patients with multiple sclerosis that described the costs attributed to each EDSS score and utilized specific inclusion criteria for the selection of 10 studies. We found that both direct and indirect costs rise continuously with increasing EDSS category, and this rise is qualitatively exponential. The rise in indirect costs appears at lower EDSS scores. The cost of a relapse occurring in any given EDSS category exceeds that associated with that particular EDSS category. Few studies comprehensively assessed the entire spectrum of the costs, and much of the literature is based on EDSS categories in coarse groupings. In spite of several variations between studies, one important conclusion that we can draw is that rise in cost is positively correlated to scores on the EDSS categories, and therefore agents with a capacity to prevent or arrest the rate of MS progression may affect the overall cost of MS.

TRIPSTAR: prioritizing oral triptan treatment attributes in migraine management.

Migraine can be associated with severe pain and is often very disabling. Optimal treatment should provide rapid and sustained, complete pain relief, be well tolerated and restore normal function. The seven commercially available triptans show differences in performance on individual treatment attributes. The TRIPSTAR multiattribute decision model compares the profiles of the oral triptans, using efficacy and tolerability data weighted for importance, to identify if measurable differences are clinically relevant. Application of the TRIPSTAR model was demonstrated at the Migraine Trust International Symposium 2002, where delegates collectively prioritized treatment attributes according to the needs of a specific patient case history. The TRIPSTAR model identified the preferred triptans for this patient. These three triptans, almotriptan 12.5 mg, eletriptan 80 mg and rizatriptan 10 mg, standout in a triptan meta-analysis, three TRIPSTAR surveys and in a demonstration of the TRIPSTAR model at a symposium in the USA. Taken together the findings suggest that some differences amongst triptans may be relevant in clinical practice.

Oral sumatriptan for acute migraine.

BACKGROUND: Migraine is a common neurovascular disorder characterized by recurrent episodes of disabling headache, autonomic nervous system dysfunction, and, in some patients, neurological aura symptoms. Sumatriptan is one of a class of selective serotonin 5-hydroxytryptamine (5-HT1B/1D) agonists (triptans) thought to relieve migraine attacks by several mechanisms, including cranial vasoconstriction and peripheral and central neural inhibition. OBJECTIVES: To describe and assess the evidence from randomized controlled trials (RCTs) concerning the efficacy and tolerability of oral sumatriptan for the treatment of a single acute attack of migraine in adults. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (Cochrane Library, Issue 4, 2001), MEDLINE (1966 through November 2001), and reference lists of articles and books. SELECTION CRITERIA: We included double-blind RCTs comparing oral sumatriptan (100 mg, 50 mg, 25 mg) with placebo, no intervention, other drug treatments, behavioral therapy, or physical therapy for the treatment of an acute attack of migraine in adults. Trials comparing different doses of sumatriptan or dosing regimens were also included. Outcomes considered were: 2-hour pain-free response, headache relief/headache intensity, and functional disability; headache recurrence; and adverse events. DATA COLLECTION AND ANALYSIS: Data were abstracted by one reviewer and over-read by the other. The two reviewers independently assessed trial quality. Information on adverse events was collected from trial reports. MAIN RESULTS: Twenty-five trials involving 16,200 participants were included. Methodological quality was generally good. Sixteen trials were placebo comparisons and showed that sumatriptan in doses of 100 mg (14 trials), 50 mg (five trials), and 25 mg (three trials) provided significantly better pain-free response (100 mg and 25 mg only), headache relief, and relief of disability at 2 hours. Numbers-needed-to-treat (NNTs) for pain-free response at 2 hours were 5.1 (3.9 to 7.1) for the 100-mg dose (n = 2221) and 7.5 (2.7 to 142) for the 25-mg dose (n = 131); there was no significant difference between the 50-mg dose and placebo for this outcome (n = 127). For headache relief at 2 hours, NNTs were 3.4 (3.0 to 4.0), 3.2 (2.4 to 5.1), and 3.4 (2.3 to 6.6) for sumatriptan 100 mg (n = 2940), 50 mg (n = 420), and 25 mg (n = 226), respectively. Precise estimates of the efficacy of the 50- and 25-mg doses relative to the 100-mg dose could not be obtained. Adverse events were more common with sumatriptan 100 mg than with placebo (risk difference [RD] = 0.14 [0.09 to 0.20]; number-needed-to-harm [NNH] = 7.1 [5.0 to 11.1]; n = 3172). RDs for the 50- and 25-mg vs. placebo comparisons were not statistically significant. REVIEWER'S CONCLUSIONS: Oral sumatriptan has been shown to be an effective drug for the treatment of a single acute attack of migraine. It is well tolerated, though minor adverse events were not uncommon in the included trials. Other triptans were generally similar in efficacy and adverse events. Among non-triptan drugs, ergotamine + caffeine was significantly less effective than sumatriptan, and other drugs have been insufficiently studied to draw firm conclusions.

Host immune responses and intestinal permeability in patients with jaundice.

BACKGROUND: Systemic endotoxaemia is implicated in the development of complications associated with obstructive jaundice. The aims of these studies were to assess the systemic immune response to intervention in patients with jaundice and to compare the effects of surgical and non-surgical biliary drainage on host immune function and gut barrier function. METHODS: In the first study, 18 jaundiced and 12 control patients were studied to assess systemic immune responses before and after intervention. In the second study, immune responses and gut barrier function were assessed following surgical and non-operative biliary decompression in 45 patients with jaundice. RESULTS: Endotoxin antibody concentrations fell significantly in patients with jaundice immediately after surgical intervention, but not after non-operative biliary drainage. This decrease was associated with a significant increase in serum P(55) soluble tumour necrosis factor (sTNF) receptor concentration (5.3 versus 10.5 ng/ml; P < 0.001), urinary excretion of P(55) TNF receptors (21.4 versus 78.8 ng/ml; P = 0.002) and intestinal permeability (lactulose : mannitol ratio 0.032 versus 0.082; P = 0.048). Intestinal permeability was significantly increased in patients with jaundice compared with controls (0.033 versus 0.015; P = 0.002). CONCLUSION: These data suggest that obstructive jaundice is associated with impaired gut barrier function and activation of host immune function that is exacerbated by intervention. Surgery causes an exaggerated pathophysiological disturbance not seen with non-operative biliary drainage procedures.

Anti-cholinergic bronchodilators versus beta2-sympathomimetic agents for acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Inhaled bronchodilators form the mainstay of treatment for acute exacerbations of COPD. Two types of agent are used routinely, either singly or in combination: anticholinergic agents and beta2-sympathomimetic agonists. OBJECTIVES: To assess the effect of anti-cholinergic agents on lung function and dyspnea in patients with acute exacerbations of COPD, compared with placebo or short-acting beta-2 agonists. SEARCH STRATEGY: A comprehensive search of the literature was carried out on MEDLINE, EMBASE, CINAHL and the Cochrane COPD Trials Register, using the terms: bronchodilator* OR ipratropium OR oxitropium. References listed in each included trial were searched for additional trial reports. SELECTION CRITERIA: Studies were included if the participants were adult patients with a known diagnosis of COPD and had symptoms consistent with criteria for acute exacerbation of COPD. All randomized controlled trials that compared inhaled ipratropium bromide or oxitropium bromide to appropriate controls were considered. Appropriate control treatments included placebo, other bronchodilating agents, or combination therapies. Studies of acute asthma or ventilated patients were excluded. DATA COLLECTION AND ANALYSIS: All trials that appeared to be relevant were assessed by two reviewers who independently selected trials for inclusion. Differences were resolved by consensus. MAIN RESULTS: Four trials compared the short-term effects of ipratropium bromide vs. a beta2-agonist. Short-term changes in FEV1 (up to 90 minutes) showed no significant difference between beta2-agonist and ipratropium bromide treated patients. The differences were similar among the studies and when combined: Weighted Mean Difference (WMD) 0.0 liters (95% Confidence Interval (95% CI) -0.19, 0.19). There was no significant additional increase in change in FEV1 on adding ipratropium to beta2-agonist: WMD 0.02 liter (95% CI -0.08, 0.12). Long-term effects (24 hours) of the ipratropium bromide and beta2-agonist treatment combination were similar: WMD 0.05 liters (95%CI -0.14, 0.05). Neither of two studies found significant changes in PaO2, either short- or long-term, with ipratropium vs. beta-agonist, although one showed an increase in PaO2 in subjects receiving ipratropium bromide at 60 minutes. Adverse drug reactions included dry mouth and tremor. REVIEWER'S CONCLUSIONS: There was no evidence that the degree of bronchodilation achieved with ipratropium bromide was greater than that using a short-acting beta2-agonist. The combination of a beta2-agonist and ipratropium did not appear to increase the effect on FEV1 more than either used alone.

Inhaled short-acting beta2-agonists versus ipratropium for acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Inhaled short acting beta2 adrenergic agonists and ipratropium bromide are both used in the treatment of acute exacerbations of chronic obstructive pulmonary disease. OBJECTIVES: In patients with acute exacerbations of COPD to: 1. To assess the efficacy of short-acting beta-2 agonists against placebo; 2. Compare the efficacy of short-acting beta-2 agonists and ipratropium. SEARCH STRATEGY: A comprehensive search of the literature was carried out of EMBASE, MEDLINE, CINAHL and the Cochrane COPD trials register was carried out using the terms: bronchodilator* OR albuterol OR metaproterenol OR terbutaline OR isoetharine OR pirbuterol OR salbutamol OR beta-2 agonist. SELECTION CRITERIA: All trials that appeared to be relevant were assessed by two reviewers who independently selected trials for inclusion. Differences were resolved by consensus. DATA COLLECTION AND ANALYSIS: All trials that appeared to be relevant were assessed by two reviewers who independently selected trials for inclusion. Differences were resolved by consensus. References listed in each included trial were searched for additional trial reports. Trials were combined using Review Manager using a fixed effects model. The size of the treatment effects were tested for heterogeneity. MAIN RESULTS: We identified no placebo-controlled comparisons of beta-2 agonists. Three studies permitted comparison of ipratropium to an inhaled beta-2 agonist. These studies included a total of 103 patients. The beta2-agonists used were: fenoterol and metaproterenol. One study was a parallel group trial of regular therapy for seven days. The other two were cross over studies of single dose treatments, with efficacy measured 90 min post dose. There was no washout period between treatments. Both treatments produced an improvement in forced expiratory volume (FEV1) after 90 min in the range 150-250 ml. The was no difference between treatments, mean difference in FEV1 10 ml; 95% CI -220, 230 ml. In one small crossover study (n=10) there was a significant improvement in arterial PaO2 after 30 minutes with ipratropium (+5.8 mm Hg +/- 3.0 (SEM)) compared to metaproterenol (-6.2 +/- 1.2 mm Hg), but this was not significant at 90 min. There were no data concerning respiratory symptoms. The crossover studies showed no evidence of an additive effect of the two treatments, although they were not designed specifically to test this. REVIEWER'S CONCLUSIONS: There are few controlled trial data concerning the use of inhaled beta2-agonist agents in acute exacerbations of COPD and none that have compared these agents directly with placebo. None of the studies used the more modern beta2-agonists used most widely in this setting (salbutamol and terbutaline). Beta2-agonists and ipratropium both produce small improvements in FEV1, but beta2-agonists may worsen PaO2 for a period. We could not draw conclusions concerning possible additive effects.

Surgical trainees' attitudes to laparoscopic cholecystectomy: a regional survey.

BACKGROUND AND STUDY AIMS: Since the introduction of laparoscopic cholecystectomy (LC), numerous articles have been written emphasising its many advantages over open cholecystectomy (OC). However, reports also highlight increased complications following LC such as bile-duct, vascular and bowel injuries. We aimed to study surgical trainees as a defined population of individuals who, with increasing exposure to cholecystectomy, would become fully aware of LC's advantages and controversies. We wished to test the hypothesis that, with increasing in-depth knowledge, they might opt for OC rather than LC if they themselves required cholecystectomy. MATERIALS AND METHODS: We conducted a postal survey of all 133 Northern Ireland surgical trainees identified as having exposure to LC during their training. Trainees were asked whether they would undergo LC and if so with which preconditions. Similarly, if they stated a preference for open cholecystectomy they were asked to state the reason. A minimum time period of 18 months was considered adequate for trainees to become relatively more experienced in this field compared with their more junior counterparts. RESULTS: A response rate of 80.5% (107/133) was achieved. A total of 51 of 107 trainees had at least 18 months' experience. Of the 107 who replied, 88.8% (95/107) would be willing to undergo LC. A total of 12 of 107 trainees would opt for OC, with twice as many experienced trainees (8 vs. 4) opting for this approach (n.s. [not significant]). Significantly more experienced trainees cited the use of laparoscopic cholangiography as a precondition for LC compared with their inexperienced counterparts (7 vs. 1, p = 0.020). Of 107 trainees, 19 would request use of the open first port (Hasson) technique; 14 of these had at least 18 months' experience (p = 0.009). CONCLUSION: Our survey confirms that the majority of trainees would be willing to undergo LC. However, increased experience of LC may alter an individual's expectations about how LC should ideally be performed.

Management of acute exacerbations of chronic obstructive pulmonary disease: a summary and appraisal of published evidence.

PURPOSE: To review critically the available data on diagnostic evaluation, risk stratification, and therapeutic management of patients with acute exacerbations of chronic obstructive pulmonary disease (COPD). DATA SOURCES: English-language articles were identified by searching MEDLINE (1966 to 2000, week 5), EMBASE (1974 to 2000, week 18), HealthStar (1975 to June 2000), and the Cochrane Controlled Trials Register (2000, Issue 1). STUDY SELECTION: The best available evidence on each subtopic was selected for analysis. Randomized trials, sometimes buttressed by cohort studies, were used to evaluate therapeutic interventions. Cohort studies were used to evaluate diagnostic tests and risk stratification. DATA EXTRACTION: Study design and results were summarized in evidence tables. Individual studies were rated by internal validity, external validity, and quality of design. Statistical analyses of combined data were not performed. DATA SYNTHESIS: Data on the utility of most diagnostic tests are limited. However, chest radiography and arterial blood gas sampling seem useful while acute spirometry does not. Identifiable clinical variables are associated with risk for relapse and risk for death after hospitalization for an acute exacerbation. Evidence of efficacy was found for bronchodilators, corticosteroids, and noninvasive positive-pressure ventilation. There is also support for the use of antibiotics in patients with more severe exacerbations. On the basis of limited data, mucolytics and chest physiotherapy do not seem to be of benefit, and oxygen supplementation seems to increase the risk for respiratory failure only in an identifiable subgroup of patients. CONCLUSIONS: Although suggestions for appropriate management can be made on the basis of available evidence, the supporting literature is scarce and further high-quality research is necessary. Such research will require an improved, generally acceptable, and transportable definition of acute exacerbation of COPD, as well as improved methods for observing and measuring outcomes.

Management of acute exacerbations of COPD: a summary and appraisal of published evidence.

STUDY OBJECTIVES: To critically review the available data on the diagnostic evaluation, risk stratification, and therapeutic management of patients with acute exacerbations of COPD. DESIGN, SETTING, AND PARTICIPANTS: English-language articles were identified from the following databases: MEDLINE (from 1966 to week 5, 2000), EMBASE (from 1974 to week 18, 2000), HealthStar (from 1975 to June 2000), and the Cochrane Controlled Trials Register (2000, issue 1). The best available evidence on each subtopic then was selected for analysis. Randomized trials, sometimes buttressed by cohort studies, were used to evaluate therapeutic interventions. Cohort studies were used to evaluate diagnostic tests and risk stratification. Study design and results were summarized in evidence tables. Individual studies were rated as to their internal validity, external validity, and quality of study design. Statistical analyses of combined data were not performed. MEASUREMENT AND RESULTS: Limited data exist regarding the utility of most diagnostic tests. However, chest radiography and arterial blood gas sampling appear to be useful, while short-term spirometry measurements do not. In terms of the risk of relapse and the risk of death after hospitalization for an acute exacerbation, there are identifiable clinical variables that are associated with these outcomes. Therapies for which there is evidence of efficacy include bronchodilators, corticosteroids, and noninvasive positive-pressure ventilation. There is also support for the use of antibiotics in patients with more severe exacerbations. Based on limited data, mucolytics and chest physiotherapy do not appear to be of benefit, and oxygen supplementation appears to increase the risk of respiratory failure in an identifiable subgroup of patients. CONCLUSIONS: Although suggestions for appropriate management can be made based on available evidence, the supporting literature is spotty. Further high-quality research is needed and will require an improved, generally acceptable, and transportable definition of the syndrome "acute exacerbation of COPD" and improved methods for observing and measuring outcomes.

Butalbital in the treatment of headache: history, pharmacology, and efficacy.

Analgesics containing butalbital compounded with aspirin, acetaminophen, and/or caffeine are widely used for the treatment of migraine and tension-type headache. The butalbital-containing compounds are efficacious in placebo-controlled trials among patients with episodic tension-type headaches. Despite their frequent clinical use for migraine, they have not been studied in placebo-controlled trials among patients with migraine. Barbiturates can produce intoxication, hangover, tolerance, dependence, and toxicity. Butalbital can result in intoxication that is clinically indistinguishable from that produced by alcohol. Butalbital-containing analgesics can produce drug-induced headache in addition to tolerance and dependence. Higher doses can produce withdrawal syndromes after discontinuation. Butalbital-containing analgesics may be effective as backup medications or when other medications are ineffective or cannot be used. Because of concerns about overuse, medication-overuse headache, and withdrawal, their use should be limited and carefully monitored.

Setting the target for a better cervical screening test: characteristics of a cost-effective test for cervical neoplasia screening.

OBJECTIVE: To determine the potential effects on costs and outcomes of changes in sensitivity and specificity with new screening methods for cervical cancer. METHODS: Using a Markov model of the natural history of cervical cancer, we estimated the effects of sensitivity, specificity, and screening frequency on cost-effectiveness. Our estimates of conventional Papanicolaou test sensitivity of 51% and specificity of 97% were obtained from a meta-analysis. We estimated the effect of reducing false-negative rates from 40-90% and increasing false-positive rates by up to 20%, independently and jointly. We varied the marginal cost of improving sensitivity from $0 to $15. RESULTS: When specificity was held constant, increasing sensitivity of the Papanicolaou test increased life expectancy and costs. When sensitivity was held constant, decreasing specificity of the Papanicolaou test increased costs, an effect that was more dramatic at more frequent intervals. Decreased specificity had a substantial effect on cost-effectiveness estimates of improved Papanicolaou test sensitivity. Most of those effects are related to the cost of evaluation and treatment of low-grade lesions. CONCLUSION: Policies or technologies that increased sensitivity of cervical cytologic screening increased overall costs, even if the cost of the technology was identical to that of conventional Papanicolaou smears. These effects appear to be caused by relatively high prevalence of low-grade lesions and are magnified at frequent screening intervals. Efficient cervical cancer screening requires methods with greater ability to detect lesions that are most likely to become cancerous.