Do the findings of case series studies vary significantly according to methodological characteristics?
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OBJECTIVES: To review the use of case series in National Institute for Clinical Excellence (NICE) Health Technology Assessment (HTA) reports, to review systematically the methodological literature for papers relating to the validity of aspects of case series design, and to investigate characteristics and findings of case series using examples from the UK's Health Technology Assessment programme. DATA SOURCES: Electronic databases. NICE website. Reports produced as part of the UK's HTA programme. REVIEW METHODS: NICE HTAs that used information from case series studies were obtained from the NICE website and a range of quality criteria applied. Searches of electronic databases, handsearched journals and the bibliographies of papers were made in order to find studies that assessed aspects of case series design, analysis or quality in relation to study validity. Hypotheses relating to the design of case series studies were developed and empirically investigated using four case examples from existing reports produced as part of the UK's HTA programme (functional endoscopic sinus surgery for nasal polyps, spinal cord stimulation for chronic back pain, percutaneous transluminal coronary angioplasty and coronary artery bypass grafting for chronic angina). Analysis was undertaken comparing studies within each review. RESULTS: There was no consensus on which case series to include in HTAs, how to use them or how to assess their quality, despite them being used in 30% of NICE HTAs. No previous studies empirically investigating methodological characteristics of case series were found. However, it is possible that the search strategy failed to find relevant studies. Poor reporting of case series characteristics severely constrained analysis and there were insufficient data to investigate all the hypotheses. Findings were not consistent across the different topics and were subject to considerable uncertainty. All the examples in our analysis were surgical interventions, which are prone to additional confounding factors due to difficulties of standardisation compared with drug treatment. Our findings may not be generalisable outside the interventions studied. The case series reports included generally exhibited poor reporting of methodological characteristics. This constrained our analysis. The use of several methods of analysis has led to apparently discrepant results. Given the number of analysis performed, the usual level of significance (p = 0.05) should be viewed with caution. The most important limitation of this study is the small number of cases on which the findings are based. The results are therefore tentative and should be viewed with caution. CONCLUSIONS: Case series are incorporated in a significant proportion of health technology assessments. Quality criteria have been used to appraise the quality of case series and decide on their inclusion in reviews of studies using this design. In this small series of case studies drawn from HTAs carried out for the NHS HTA programme, little evidence was found to support the use of many of the factors included in quality assessment tools. Importantly, no relationship was found between study size and outcome across the four examples studied. Isolated examples of a potentially important relationship between other methodological factors and outcome were shown, such as blinding of outcome measurement, but these were not shown consistently across the small number of examples studied. This study is based on a very small sample of studies and should therefore be considered as exploratory. Further investigation of the relationship between methodological features and outcome is justified given the frequency of use of case series in health technology assessments. Further research into the methodological features of case series and their outcome is justified in a wider sample of technologies and larger sets of case series. Value of information analyses including case series could be explored. Further exploration of the differences between case series and randomised controlled trial results, preferably using registry or comprehensive case series data, would be valuable. (+info)
Direct medical cost of asthma in Ankara, Turkey.
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BACKGROUND: There has been no documented data regarding the cost of asthma in our country. OBJECTIVE: In this 1-year prospective study, we aimed to determine the annual cost of asthma in Ankara, Turkey. METHODS: Direct medical cost analysis was performed in 118 patients. RESULTS: Mean annual direct medical costs of asthma were USD 1,465.7 +/- 111.8 per capita. Medication cost comprised the majority (81%) of the total direct cost. Mean direct medical costs according to the stage of disease were USD 172.5 +/- 51.7, 860.7 +/- 70.2, 1,671.6 +/- 141.8 and 3,491.9 +/- 417.6 for stage 1 (n = 4), 2 (n = 54), 3 (n = 46) and 4 (n = 14) patients, respectively. CONCLUSIONS: In this first study to document the cost of asthma for our region, direct cost of asthma was found to be increased with the severity of the illness. Considering the fact that medication cost comprises the major fraction of the direct cost, cost-effectiveness trials to determine the effective treatment with optimal cost for different asthma stages should be the next step. (+info)
Influence of fluticasone propionate on the production of vascular endothelial growth factor and basic fibroblast growth factor from nasal fibroblasts in vitro.
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The influence of fluticasone propionate (FP) on vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) production from nasal polyp fibroblasts (NPFs) was examined in vitro. NPFs, at a density of 2.5 x 10(5) cells/ml, were stimulated with 25 ng/ml TNF-alpha in the presence or absence of FP for 24 h. FP at more than 10(-6) M could suppress VEGF production from NPFs. bFGF production induced by TNF-alpha stimulation was also suppressed by FP, when the agent was added to cell cultures at more than 10(-7) M. The present results also showed the suppressive activity of FP on mRNA expression for VEGF and bFGF, which were increased by TNF-alpha stimulation. (+info)
Eosinophils in chronically inflamed human upper airway tissues express transforming growth factor beta 1 gene (TGF beta 1).
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Transforming growth factor beta (TGF beta) is a multifunctional protein which has been suggested to play a central role in the pathogenesis of chronic inflammation and fibrosis. Nasal polyposis is a condition affecting the upper airways characterized by the presence of chronic inflammation and varying degrees of fibrosis. To examine the potential role of TGF beta in the pathogenesis of this condition, we investigated gene expression and cytokine production in nasal polyp tissues as well as in the normal nasal mucosa. By Northern blot analysis using a porcine TGF beta 1 cDNA probe, we detected TGF beta 1-specific mRNA in nasal polyp tissues, as well as in the tissue from a patient with allergic rhinitis, but not in the normal nasal mucosa. By the combination of tissue section staining with chromotrope 2R with in situ hybridization using the same TGF beta 1 probe, we found that approximately 50% of the eosinophils infiltrating the polyp tissue express the TGF beta 1 gene. In addition, immunohistochemical localization of TGF beta 1 was detected associated with extracellular matrix as well as in cells in the stroma. These results suggest that in nasal polyposis where eosinophils are the most prevalent inflammatory cell, TGF beta 1 synthesized by these cells may contribute to the structural abnormalities such as stromal fibrosis and basement membrane thickening which characterize this disease. (+info)
Bacteriology of chronic maxillary sinusitis associated with nasal polyposis.
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Aspirates from 48 chronically inflamed maxillary sinuses from patients who had nasal polyposis were processed for aerobic and anaerobic bacteria. Bacterial growth was present in 46 (96%) specimens. Aerobic or facultative bacteria were present in 6 (13%) specimens, anaerobic bacteria alone in 18 (39%), and mixed aerobic and anaerobic bacteria in 22 (48%). There were 110 bacterial isolates (2.4 per specimen). Thirty-nine of the isolates were aerobic or facultative organisms (0.85 per specimen). The predominant aerobic or facultative organisms were: Staphylococcus aureus, microaerophilic streptococci, Haemophilus influenzae and Moraxella catarrhalis. Seventy-one anaerobes were isolated (1.5 per specimen), Peptostreptococcus spp., Prevotella spp., Porphyromonas asaccharolytica and Fusobacterium spp. being predominant. These findings illustrate for the first time the presence of polymicrobial aerobic-anaerobic flora in patients with chronic maxillary sinusitis who had nasal polyposis. (+info)
Bacterial induction of TNF-alpha converting enzyme expression and IL-6 receptor alpha shedding regulates airway inflammatory signaling.
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Airway epithelial cells have a major role in initiating inflammation in response to bacterial pathogens. Through the immediate induction of CXCL8 and cytokine expression, polymorphonuclear cells are mobilized and activated to eradicate the infecting organisms. However, the influx of polymorphonuclear cells and the effects of their toxic exoproducts impede respiratory function. We postulated that respiratory epithelial cells must also participate in the regulation of their own proinflammatory signaling. Both Staphylococcus aureus and Pseudomonas aeruginosa were found to potently activate IL-6 expression immediately upon contact with epithelial cells, and by 1 h induced TNF-alpha converting enzyme (TACE) transcription. By 4 h of bacterial exposure, TACE colocalized with IL-6Ralpha on the apical surface of airway cells, and by 24 h, soluble IL-6Ralpha accumulated in the cell culture supernatant. Epithelial IL-6 and soluble IL-6Ralpha were shown to participate in trans-signaling, interacting with membrane-associated gp130 to activate CCL-2 expression and inhibit additional CXCL8 production. Thus, bacteria are physiological activators of TACE expression, which provides a mechanism to regulate inflammatory signaling that is initiated by airway epithelial cells. (+info)
Invasive aspergillosis involving multiple paranasal sinuses--a case report.
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A case of invasive multiple paranasal sinus aspergillosis with bony involvement is reported. A young immunocompetent lady presented with bilateral nasal obstruction due to polyps. Radiologically and histopathologically a fungal cause was kept a possibility, and the diagnosis of Aspegillus fumigatus was established by demonstration of acute angle branching septate hyphae on direct wet mount and repeated isolation in culture. Patient responded favourably to surgical excision of polyps and oral itraconazole post operatively. (+info)
Downregulation of peroxisome proliferator-activated receptors (PPARs) in nasal polyposis.
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BACKGROUND: Peroxisome proliferator-activated receptor (PPAR) alpha, betadelta and gamma are nuclear receptors activated by fatty acid metabolites. An anti-inflammatory role for these receptors in airway inflammation has been suggested. METHODS: Nasal biopsies were obtained from 10 healthy volunteers and 10 patients with symptomatic allergic rhinitis. Nasal polyps were obtained from 22 patients, before and after 4 weeks of local steroid treatment (fluticasone). Real-time RT-PCR was used for mRNA quantification and immunohistochemistry for protein localization and quantification. RESULTS: mRNA expression of PPARalpha, PPARbetadelta, PPARgamma was found in all specimens. No differences in the expression of PPARs were obtained in nasal biopsies from patients with allergic rhinitis and healthy volunteers. Nasal polyps exhibited lower levels of PPARalpha and PPARgamma than normal nasal mucosa and these levels were, for PPARgamma, further reduced following steroid treatment. PPARgamma immunoreactivity was detected in the epithelium, but also found in smooth muscle of blood vessels, glandular acini and inflammatory cells. Quantitative evaluation of the epithelial immunostaining revealed no differences between nasal biopsies from patients with allergic rhinitis and healthy volunteers. In polyps, the PPARgamma immunoreactivity was lower than in nasal mucosa and further decreased after steroid treatment. CONCLUSION: The down-regulation of PPARgamma, in nasal polyposis but not in turbinates during symptomatic seasonal rhinitis, suggests that PPARgamma might be of importance in long standing inflammations. (+info)