Cross-cultural adaptation and psychometric properties of the Brazilian-Portuguese version of the VSP-A (Vécu et Santé Perçue de l'Adolescent), a health-related quality of life (HRQoL) instrument for adolescents, in a healthy Brazilian population.

BACKGROUND: Health-related quality of life (HRQoL) assessment, encompassing the adolescents' perceptions of their mental, physical, and social health and well-being is increasingly considered an important outcome to be used to identify population health needs and to provide targeted medical care. Although validated instruments are essential for accurately assessing HRQoL outcomes, there are few cross-culturally adapted tools for use in Brazil, and none designed exclusively for use among adolescents. The Vécu et Santé Perçue de l'Adolescent (VSP-A) is a generic, multidimensional self-reported instrument originally developed and validated in France that evaluates HRQoL of ill and healthy adolescents. PURPOSE: To cross-culturally adapt and validate the Brazilian-Portuguese version of the VSP-A, a generic HRQoL measure for adolescents originally developed in France. METHODS: The VSP-A was translated following a well-validated forward-backward process leading to the Brazilian version. The psychometric evaluation was conducted in a sample of 446 adolescents (14-18 years) attending 2 public high schools of São Gonçalo City. The adolescents self-reported the Brazilian VSP-A, the validated Psychosomatic Symptom Checklist and socio-demographic information. A retest evaluation was carried out on a sub-sample (n = 195) at a two-week interval. The internal construct validity was assessed through confirmatory factor analysis (CFA), multi-trait scaling analyses, Rasch analysis evaluating unidimensionality of each scale and Cronbach's alpha coefficients. The reproducibility was evaluated by intra-class correlation coefficients (ICC). Zumbo's ordinal logistic regression analysis was used to detect differential item functioning (DIF) between the Brazilian and the French items. External construct validity was investigated testing expected differences between groups using one-way analysis of variance (ANOVA), Mann-Whitney tests and the univariate general regression linear model. RESULTS: CFA showed an acceptable fit (RMSEA=0.05; CFI=0.93); 94% of scaling success was found for item-internal consistency and 98% for item discriminant validity. The items showed good fit to the Rasch model except 3 items with an INFIT at the upper threshold. Cronbach's Alpha ranged from 0.60 to 0.85. Test-retest reliability was moderate to good (ICC=0.55-0.82). DIF was evidenced in 4 out of 36 items. Expected patterns of differences were confirmed with significantly lower physical, psychological well being and vitality reported by symptomatic adolescents. CONCLUSIONS: Although DIF in few items and responsiveness must be further explored, the Brazilian version of VSP-A demonstrated an acceptable validity and reliability in adolescents attending school and might serve as a starting point for more specific clinical investigations.

Children proxies' quality-of-life agreement depended on the country using the European KIDSCREEN-52 questionnaire.

OBJECTIVE: The aims of this study were to assess the level of agreement and the magnitude of discrepancies between children and their parents, and whether these levels of agreement/discrepancy depend on the country of living, the domains of quality of life assessed, the age and gender of the children, and other background variables. STUDY DESIGN AND SETTING: The KIDSCREEN pilot study involved 2,526 youth-proxy pairs in seven European countries. The health-related quality of life (HRQoL) of children and their parents as proxy has been assessed in parallel using a 10-dimension KIDSCREEN-52 Pilot test questionnaire. RESULTS: For the 10 dimensions, the mean difference between proxy and youth score decreases as the HRQoL level increases. Physical and cognitive domains showed the major agreement between youth and proxy measure. Social and psychological domains presented the main discrepancies. Linear regression models highlighted that the agreement was depending on the country for the 10 dimensions. Impact of age and gender on agreement were not consistent across the 10 dimensions. CONCLUSION: Agreement is higher for the girls than for the boys and for the adolescents than for children. To further explore the country effect on agreement, results need replication in representative studies.

One hundred consecutive pneumonectomies after induction therapy for non-small cell lung cancer: an uncertain balance between risks and benefits.

OBJECTIVE: We sought to assess postoperative outcome after pneumonectomy after neoadjuvant therapy in patients with non-small cell lung cancer. METHODS: This retrospective study included 100 patients treated from January 1989 through December 2003 for a primary lung cancer in whom pneumonectomy had been performed after an induction treatment. Surgical intervention had not been considered initially for the following reasons: N2 disease (stage IIIA, n = 79), doubtful resectability (stage IIIB [T4, N0], n = 19), and M1 disease (stage IV [T2, N0, M1, solitary brain metastasis], n = 2). All patients received a 2-drug platinum-based regimen with a median of 2.5 cycles (range, 2-4 cycles), and 30 had associated radiotherapy (30-45 Gy). RESULTS: There were 55 right and 45 left resections. Overall 30-day and 90-day mortality rates were 12% and 21%, respectively. At multivariate analysis, one independent prognostic factor entered the model to predict 30-day mortality: postoperative cardiovascular event (relative risk, 45.7; 95% confidence interval, 3.7-226.7; P = .001). Four variables predicted 90-day mortality: age of more than 60 years (relative risk, 5.06; 95% confidence interval, 1.47-17.48; P = .01), male sex (relative risk, 8.25; 95% confidence interval, 1.01-67.34; P = .049), postoperative respiratory event (relative risk, 3.64; 95% confidence interval, 1.14-9.37; P = .007), and postoperative cardiovascular event (relative risk, 7.84; 95% confidence interval, 3.12-19.71; P < .001). Estimated overall survivals in 90-day survivors were 35% (range, 29%-41%) and 25% (range, 19.3%-30.7%) at 3 and 5 years, respectively. At multivariate analysis, one independent prognostic factor entered the model: pathologic stage III-IV residual disease (relative risk, 1.89; 95% confidence interval, 1.09-3.26; P = .022). CONCLUSIONS: Pneumonectomy after induction therapy is a high-risk procedure, the survival benefit of which appears uncertain.

A meta-analytical approach to the efficacy of antihypertensive drugs in reducing blood pressure.

INTRODUCTION: Hypertension constitutes a veritable public health issue. Several classes of drugs are available for the treatment of hypertension. The objective of this meta-analytical approach was to assess the efficacy of antihypertensive drugs most commonly used in France in reducing clinical SBP and DBP. METHODS: The antihypertensive drugs selected were hydrochlorothiazide, indapamide sustained release (SR), furosemide and spironolactone for diuretics; amlodipine and lercanidipine for calcium channel antagonists; atenolol for beta-adrenoceptor antagonists (beta-blockers); enalapril and ramipril for ACE inhibitors; and candesartan cilexetil, irbesartan, losartan, and valsartan for angiotensin II receptor antagonists. The trials selected were published between 1973 and 2004, evaluated monotherapy with trial drugs as fixed-dosage or with dosage increase, and assessed blood pressure reduction between 2 and 3 months. The analysis method used was based on the calculation of the sum weighted for the trial size. RESULTS: A total of 72 trials (comprising 9094 patients) were selected and analyzed. No trial evaluating furosemide or spironolactone satisfied the inclusion criteria for this analysis. For SBP, the reduction was more marked with diuretics, calcium channel antagonists, and ACE inhibitors. Of all the drugs studied, indapamide SR gave the greatest SBP reduction (-22.2 mm Hg). Evaluated therapeutic classes had a similar magnitude of effect on DBP, i.e. reduction between -11.4 mm Hg with beta-adrenoceptor antagonists and -10.3 mm Hg with angiotensin II type 1 receptor antagonists. CONCLUSION: Indapamide SR 1.5 mg appeared to be the most effective drug for a significant reduction in SBP within 2-3 months, which is an essential element in optimizing cardiovascular prevention among hypertensive patients. The clinical application of these results should take into consideration all the limitations discussed in this analysis.

Does the extent of lymph node dissection influence outcome in patients with stage I non-small-cell lung cancer?

OBJECTIVE: To assess the therapeutic effect of the extent of lymph node dissection performed in patients with a stage pI non-small-cell lung cancer (NSCLC). METHODS: We analysed data on 465 patients with stage I NSCLC who were treated with surgical resection and some form of lymph node sampling. The median number of lymph node sampled was 10 and the median number of ipsilateral mediastinal lymph node stations sampled was two. We chose to define a procedure that harvested 10 or more lymph nodes and sampled two or more ipsilateral mediastinal stations as a lymphadenectomy, by contrast with sampling when one or both criteria were not satisfied. The effect of the surgical techniques: lymph node sampling (LS; n=207) vs. lymphadenectomy (LA; n=258) on 30-day mortality and overall survival were investigated. RESULTS: A total of 6244 lymph nodes was examined, including 4306 mediastinal lymph nodes. The mean (+/-SD) numbers of removed lymph nodes were 7+/-6.1 per patient following LS vs.18.6+/-9.3 following LA (P=0.001). An average mean of 1+/-0.90 mediastinal lymph node station per patient was sampled following LS vs. 2.7+/-0.8 following LA (P<10(-6)). Overall 30-day mortality rates were 2.4 and 3.1%, respectively. LA was disclosed as a favourable prognosticator at multivariate analysis (Hazard Risk: 1.43; 95% Confidence Interval: 1.00-2.04; P=0.048), together with younger patient age, absence of blood vessels invasion, and smaller tumour size. CONCLUSIONS: Importance of lymph node dissection affects patients outcome, while it does not enhance the operative mortality. A minimum of 10 lymph nodes assessed, and two mediastinal stations sampled are suggested as possible pragmatic markers of the quality of lymphadenectomy.

In vitro and in vivo methotrexate disposition in alveolar macrophages: comparison of pharmacokinetic parameters of two formulations.

MTX-liposomes, prepared with a polymerised core (LSP), were administered in anaesthetised rats by pulmonary instillation versus free drug. No toxicological effects were macroscopically observed. After each time point: 15, 30, 60 and 90 min, animals were humanely killed and analyses of radio-signal were done. This approach allowed recovery of MTX or breakdown products within biological samples. Previously, kinetics of MTX cellular uptake was performed to identify the cytotoxic concentration of drug formulation for human macrophage. Flow cytometry was set-up to characterise liposomal uptake by ex vivo pulmonary macrophage. Cells were isolated by bronchioloalveolar washes from animals. Results have shown clear different pharmacokinetic parameters between free MTX and the liposomal form of MTX. Unlike classical liposomes, which are mainly taken up by the reticulo-endothelial system, LSP-MTX was not targeted to spleen or kidney. The route of administration could be an explanation of this phenomenon. In addition, LSP-MTX was more retained by the lung tissue. Moreover, free form of the drug reaches easily lymph node. This latest result should be taken into consideration for neoplasic disease and more specifically when lymph nodes are a way for pulmonary metastasis. Finally, LSP-MTX should be tested in physio-pathological model of lung cancer to evaluate the influence of the variation of liposomal formulation pharmacokinetic parameters on the drug efficacy.

Development of a growth hormone injection questionnaire for adolescents.

We developed an instrument to assess feelings about self-injection of growth hormone (GH) in adolescents with growth disorders. Summary scores did not differ significantly by cohort, age, gender, or diagnosis. Adolescents who were more comfortable with GH injections had higher health-related quality of life, functional capacity, and self-control.

Testing the structural and cross-cultural validity of the KIDSCREEN-27 quality of life questionnaire.

OBJECTIVES: The aim of this study is to assess the structural and cross-cultural validity of the KIDSCREEN-27 questionnaire. METHODS: The 27-item version of the KIDSCREEN instrument was derived from a longer 52-item version and was administered to young people aged 8-18 years in 13 European countries in a cross-sectional survey. Structural and cross-cultural validity were tested using multitrait multi-item analysis, exploratory and confirmatory factor analysis, and Rasch analyses. Zumbo's logistic regression method was applied to assess differential item functioning (DIF) across countries. Reliability was assessed using Cronbach's alpha. RESULTS: Responses were obtained from n = 22,827 respondents (response rate 68.9%). For the combined sample from all countries, exploratory factor analysis with procrustean rotations revealed a five-factor structure which explained 56.9% of the variance. Confirmatory factor analysis indicated an acceptable model fit (RMSEA = 0.068, CFI = 0.960). The unidimensionality of all dimensions was confirmed (INFIT: 0.81-1.15). Differential item functioning (DIF) results across the 13 countries showed that 5 items presented uniform DIF whereas 10 displayed non-uniform DIF. Reliability was acceptable (Cronbach's alpha = 0.78-0.84 for individual dimensions). CONCLUSIONS: There was substantial evidence for the cross-cultural equivalence of the KIDSCREEN-27 across the countries studied and the factor structure was highly replicable in individual countries. Further research is needed to correct scores based on DIF results. The KIDSCREEN-27 is a new short and promising tool for use in clinical and epidemiological studies.

Validation of the European proxy KIDSCREEN-52 pilot test health-related quality of life questionnaire: first results.

PURPOSE: The KIDSCREEN project aims to develop a European cross-cultural generic self-administered Health-Related Quality of Life (HRQoL) instrument for children and adolescents. Proxy measures HRQoL should be a useful and practical alternative to assess children's HRQoL. The KIDSCREEN pilot study involved 3988 children and 2526 child-proxy pairs in seven European countries (Austria, Switzerland, Germany, Spain, France, United Kingdom, and The Netherlands). The proxy instrument is based on the model developed from the children and adolescents reports. The aim of this study is to assess the psychometric properties of the proxy measure in terms of reliability and construct and external validity. METHODS: Confirmatory factor analysis (CFA) of the parent's data allows testing of the multidimensional structure of the proxy measure. Rasch analysis evaluates the scalability of each dimension. The mutltitrait-multimethod (MTMM) model assesses the trait validity through CFA. The agreement between children and proxies reports has been assessed using the Intraclass Correlation Coefficient (ICC). RESULTS: CFA indicates that the children's model is adequate to the parents' data. Reliability is satisfactory for every dimension (CFI = .957). For every dimension, Rasch analysis indicates that items form a unidimensional continuum. MTMM results confirm the trait validity of the instrument. Higher agreement was found for the physical well being dimension (ICC=.52) and school/cognitive functioning (ICC=.52). Adolescents showed higher agreement than the children, and girls higher than boys. Children with physical chronic health conditions showed higher agreement for several domains: physical and psychological well-being, social support, and school environment. CONCLUSIONS: Exploring different facets of validity showed satisfactory results. This new instrument provides a promising measure to further assess the relationships between youth and proxy reports.

Brief report: a quality of life instrument for adolescents with growth disorders.

This study assessed the psychometric properties of a recently developed health-related quality of life (HRQOL) instrument (Vécu et Santé Perçue de l'Adolescent -Malade, VSP-AM) in 172 adolescents receiving growth hormone. The VSP-AM was cross-culturally adapted into English and tested for internal consistency (alpha=0.78-0.89 subscales, 0.74 Summary Score), construct and criterion validity, and responsiveness. Correlations with other scales demonstrated convergent validity. Adolescents who reported HRQOL as high or low had significantly different scores (all p<0.001). Adolescents receiving growth hormone therapy differed significantly from adolescents with medical, surgical or psychiatric disorders. The VSP-AM shows reliability and validity for HRQOL measurement in adolescents with growth disorders.

Long-term outcome after ampullectomy for ampullary lesions associated with familial adenomatous polyposis.

PURPOSE: Up to 90 percent of patients with familial adenomatous polyposis develop adenomas in the upper gastrointestinal tract. Besides pancreaticoduodenectomy, which remains indicated in duodenal and ampullary cancer, less aggressive surgical procedure (such as ampullectomy) must be evaluated in selected patients with familial adenomatous polyposis patients presenting low-risk benign duodenal adenomas. METHODS: From 1995 to 2000, we performed a retrospective, observational study, which included eight patients (5 females) with familial adenomatous polyposis underwent ampullectomy (with frozen sections) for presumed benign polyposis lesions. Six patients had an ileal pouch-anal anastomosis performed 2 to 27 years before ampullectomy. The remaining two patients had ampullectomy during the same operation than ileal pouch-anal anastomosis. RESULTS: No patient died postoperatively. Mean hospital stay was 15 +/- 6.5 (range, 10-21) days. There was one major complication (pancreatic fistula), which was treated conservatively. Final pathologic examination of the specimens revealed that three patients had a severe dysplasia. Mean follow-up of the patients was 58 +/- 37 (range, 24-119) months. During endoscopic follow-up, although all the patients underwent endoscopic resection of duodenal polyps, none presented recurrence at the ampullectomy site. CONCLUSIONS: Ampullectomy could be safely proposed in selected familial adenomatous polyposis patients. Our low morbidity and the absence of recurrence after almost five years of follow-up suggests that such conservative treatment could be proposed before pancreaticoduodenectomy in patients with high-risk ampullary adenomas without invasive carcinoma.

Severe imbalance of IL-18/IL-18BP in patients with secondary hemophagocytic syndrome.

Hemophagocytic syndrome (HPS) is characterized by an uncontrolled and poorly understood activation of T-helper 1 (Th-1) lymphocytes and macrophages. We studied 20 patients with HPS secondary to infections, autoimmune disease, lymphoma, or cancer and observed that the concentrations of serum interleukin 18 (IL-18), a strong inducer of Th-1 responses, interferon gamma (IFN-gamma) production, and stimulation of macrophages and natural killer (NK) cells were highly increased in HPS but not in control patients. In contrast, concentrations of its natural inhibitor, the IL-18 binding protein (IL-18BP), were only moderately elevated, resulting in a high level of biologically active free IL-18 in HPS (4.6-fold increase compared with controls; P < .001). Free IL-18 but not IL-12 concentrations significantly correlated with clinical status and the biologic markers of HPS such as anemia (P < .001), hypertriglyceridemia, and hyperferritinemia (P < .01) and also with markers of Th-1 lymphocyte or macrophage activation, such as elevated concentrations of IFN-gamma and soluble IL-2 and tumor necrosis factor alpha (TNF-alpha) receptor concentrations. Despite high IL-18 elevation, in vitro NK-cell cytotoxicity was severely impaired in HPS patients, in part due to NK-cell lymphopenia that was observed in a majority of patients but also secondary to an intrinsic NK-cell functional deficiency. We concluded that a severe IL-18/IL-18BP imbalance results in Th-1 lymphocyte and macrophage activation, which escapes control by NK-cell cytotoxicity and may allow for secondary HPS in patients with underlying diseases.

Vascular cell adhesion molecule-1 (VCAM-1) plays a central role in the pathogenesis of severe forms of vasculitis due to hepatitis C-associated mixed cryoglobulinemia.

BACKGROUND/AIMS: To better characterize the molecules involved in leukocyte tissue infiltration during hepatitis C-mixed cryoglobulinemia (HCV-MC)-associated vasculitis. METHODS: The involvement of ELAM, ICAM-1 and VCAM-1 was evaluated in 36 patients with HCV-MC vasculitis using three different approaches: concentrations of soluble forms by specific ELISA, tissue expression by immunohistochemistry on patients nerve biopsies, endothelial expression by FACS analysis, on cells activated in vitro by cryoprecipitates purified from HCV-MC patients. RESULTS: Concentrations of sVCAM-1 were significantly elevated in the serum of HCV-MC patients compared to HCV patients without MC, the highest concentrations being found in severe vasculitis. VCAM-1 expression was detected on blood vessels from nerve biopsies performed in patients with severe vasculitis. When added to endothelial cells in vitro, HCV-MC patients cryoprecipitate induced VCAM-1 but also ELAM and ICAM-1 expression possibly through a mechanism due to the C1q complement fraction interaction with endothelial cells, since C1q was consistently present in the cryoprecipitates. CONCLUSIONS: VCAM-1 is mainly involved in the pathogenesis of HCV-MC-associated severe vasculitis and may be a potential interesting therapeutic target.

Comparison of escitalopram and citalopram efficacy: A meta-analysis.

OBJECTIVE Escitalopram is a new selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of major depressive disorder (MDD) and panic disorder. Escitalopram is the therapeutically active enantiomer of citalopram. Its efficacy in the treatment of MDD was compared to that of citalopram. METHODS A quantitative meta-analysis was applied to 1262 patients in four randomised clinical trials; the comparison was based on response rate and mean change from baseline in the Montgomery-Åsberg depression rating scale (MADRS) total score at week 8. Complementary analyses were performed on early MADRS change from baseline (week 1), in very severely depressed patients (baseline MADRS total score ≥35) and on the influence of the level of severity at baseline. RESULTS Compared with citalopram, escitalopram-treated patients showed significantly higher response rates and increased mean change from baseline in MADRS at weeks 1 and 8. The superiority of escitalopram over citalopram was more pronounced in very severely depressed patients. This superiority was further shown to increase with degree of severity of the depression. The robustness of meta-analysis results was supported by sensitivity analyses. The clinical superiority of escitalopram versus citalopram is consistent with the results of preclinical pharmacological studies. CONCLUSION Escitalopram was shown to be an effective therapeutic treatment for MDD, presenting significant advantages over citalopram.