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The tumour biology of non-small cell bronchial cancer integrates recent developments and a dynamic schema of the phenomena of tumour progression and diffusion of the metastatic disease. There is no leap of known biological disruption between Stage II and Stage III. The latter is defined by anatomical criteria and is a transition in the continuum of the natural history of these cancers. The moto for the tumour progression is the genotypic instability and phenotypic diversification. Metastatic microscopic disease constitutes the first cause of failure in the treatment of Stage III non-small cell bronchial cancer. Among prognostic factors for survival emphasis is placed on the alterations of p53 expression, different types of aneuploidy, anomalies of the expression of cellular adhesion molecules and finally, tumour diversification towards a metastatic phenotype.

We studied the influence of TSH suppressive therapy combined with carbimazole (CBZ) on treatment outcome in Graves' disease.Open non-randomized prospective study.University Hospital of Montpellier, France.Sixty-six consecutive patients without prior treatment were included. All the patients were treated initially with 30 mg of CBZ. After 1 month of treatment, one group continued CBZ alone (n = 23), another group received a combination of CBZ plus T3 (n = 19) and a third group received CBZ and 3,5,3'-triiodothyroacetic acid (Triac, n = 24). Therapy was stopped when remission was obtained based on clinical euthyroidism, normalization of FT4 and of early radioiodine uptake. Nine patients with medical treatment failure or major side effects requiring to stop antithyroid drugs underwent surgery or radioiodine therapy. Nine patients were lost to follow-up. The remaining 48 patients were available for analysis of both remission and relapse.The median duration of therapy was 18 months (range, 4-41 months). Based on clinical examination, goitre size at 4 months decreased more in the CBZ + T3 and CBZ + Triac groups than in the CBZ group (P = 0.02). The overall remission rate tended to be higher in the groups treated with CBZ + T3 and CBZ + Triac than in the group treated with CBZ alone, but the difference did not reach statistical significance (P = 0.17). No difference in the relapse rate was observed between the three groups.TSH suppression combined with CBZ has little or no effect on remission and relapse rates in Graves' disease patients.

Because of the increasing role of post-anaesthesia care in anaesthetic activity, the explicative value of various factors on post-anaesthesia length of stay (POLS) was tested.Retrospective study.Population of 38,655 patients admitted to the post-anaesthesia care unit (PACU) between 1990 and 1994.Multivariate analysis (semiparametric Cox model) of POLS.Overall 71% of the patients stayed less than four hours in PACU. Average POLS did not vary with years. Eleven variables were related to POLS, with an odds-ratio (OR) between 0.75 and 0.77 (negative link) or between 1.22 and 2.77 (positive link). A comparison of the OR for years 1990 to 1994 indicated major variations for the following three variables: neurosurgery, mechanical ventilation in PACU, low occupancy rate in the PACU at the time of discharge.POLS are linked with various factors whose changes in explicative value can be analysed chronologically. However, other methods remain necessary in order to evaluate the impact of organisational modifications, as the introduction of objective criteria for discharge.

Background The Treat to Target and EULAR recommendations highlighted the need for achieving and maintaining remission in patients with early RA. We investigated if early RA patients with persistent moderate disease activity during the first year have in daily life a worst 3 to 5 year outcome than patients who achieved clinical remission. Methods The ESPOIR cohort included 813 patients with early arthritis in at least 2 joints of less than 6 months disease duration. They were treated according to standard of care. Within the 573 patients who had a 5 year follow-up, 93 % fulfilled the ACR/EULAR criteria for RA. This study compared patients who were in persistent (at both the month 6 and month 12 visits) DAS28 remission (group.1) versus those who were in persistent (at both the M6 and M12 visits) moderate disease activity (DAS28>3.2 and ≤5.1)(group.2). The primary outcome measure was radiographic progression ((modified Total Sharp Score (mTSS)) at month 36. Secondary endpoints were clinical remission (DAS28, SDAI, ACR/EULAR), HAQ-DI, number of missed workdays at month 36 and 60. Fisher exact test was used to compare categorical variables and Kruskal-Wallis test for quantitative variables. Logistic regression analysis was performed to determine confounding factors of outcome. Results Baseline characteristics were not significantly different between groups. Patients with persistent moderate disease activity during the first year, had greater radiographic progression, higher HAQ disability and number of missed days and lower rate of remission than those who achieved persistent remission (table). Conclusions This study demonstrated that early RA patients with persistent moderate disease activity during the first year of the disease had a worst outcome than patients who achieved clinical remission. Moderate disease activity state had substantial impact on structure, function and health outcomes. Patients should benefit from more intensive therapeutic strategy. Disclosure of Interest B. Combe: None Declared, I. Logeart Employee of: Pfizer, M. Belkacemi: None Declared, T. Schaeverbeke: None Declared, J.-P. Daures: None Declared, M. Dougados: None Declared

Etanercept, a soluble tumour necrosis factor α (TNFα) receptor fusion protein, may be combined with methotrexate (MTX) in severe rheumatoid arthritis (RA).1 Etanercept is generally given to patients treated with MTX who have an inadequate response. However, MTX could be introduced to patients who have already been treated with etanercept and who initially had a good response but subsequently a secondary failure. It was decided to evaluate, in an open prospective study, the clinical, biological, and functional benefit of the secondary addition of MTX in patients with RA with an inadequate response to etanercept alone. A cohort of 93 patients with active and severe RA was observed for a mean duration of 8 months (range 1–20). The group comprised 75 women, 18 men, with an average age of 49.5 years (range 17–75), and positive rheumatoid factor …

The effectiveness of the association of lactulose with neomycin in the treatment of acute hepatic encephalopathy has never been assessed. The aim of this study was to compare the effects of lactulose-neomycin combination versus placebo in acute hepatic encephalopathy.Eighty patients with cirrhosis were randomly treated for 5 days with placebo (n = 40) or with lactulose-neomycin (n = 40). Both groups were similar for all variables.The course of encephalopathy was similar in both groups. In the lactulose-neomycin group: 26 PATIENTS recovered, 3 remained unchanged, 3 worsened, 6 died, 2 were lost to follow-up. In the placebo group: 28 recovered, 2 remained unchanged, 2 worsened, 6 died, one was lost the follow-up, one dropped out of the study. Lactulose-neomycin treatment was not well tolerated in a significant number of patients.Lactulose-neomycin combination should not be used in the treatment of acute hepatic encephalopathy.

Locally advanced non-small cell lung cancers have a poor prognosis following surgery alone when this has been possible, because of a high rate of local and metastatic relapses. Probability of five years survival for these patients ranges between 5 and 15%. Thus, locally advanced non small cell lung cancer for which resection is potentially possible but poorly curative are usually designated as marginally resectable. Adjuvant postoperative chemotherapy or radiation therapy hardly seem to improve survival. Therefore, other combined modality treatments might be proposed. Neoadjuvant chemotherapy may be used for non small cell lung cancer in an attempt (a) to improve complete resection rate and (b) to treat non-detectable metastatic disease. Numerous phase II studies have demonstrated the faisability of this combined modality in locally advanced non small cell lung cancers, particularly in stage N2 patients. Until the results of the ongoing phase III studies would be known, neoadjuvant chemotherapy might be considered as an investigational approach.

The French health policy PMSI project (Program for a Medical Information System) is mainly aimed at development of cost analysis based on diagnosis related groups. An indicator of the relative costs of anaesthetics, the relative complexity index (ICR beta), was defined as the result of a computation of different indexes of surgical and anaesthetic procedures such as duration, patients ASA status, degree of emergency, stay in the recovery room. The aims of this study were 1) to analyze relative part of each index in ICR beta value and in ICR beta variance and 2) to assess the value of ICR beta as a cost or a complexity index. The study included 14,435 anaesthetics analyzed with the Dunn and Clarks multiple linear regression. Mean ICR beta was 267.28. The duration of the procedure accounted for 46% of the ICR beta value and surgery for 25%. The anaesthesia and the recovery accounted for 15% of the ICR beta value, but only for 0.0341 and 0.0347 respectively of the ICR beta variance. The product of the surgical procedure index by the ASA status index accounted for 0.259 of the ICR beta variance and the duration index for 0.650. The comparison of homogeneous groups with regard to the surgical procedure shows that intravenous anaesthesia accounts for 12.4% of the ICR beta value, inhalational anaesthesia for 13.84%, but exceeds 15% for regional anaesthesia (44.5% for caudal anaesthesia). For appendectomies (n = 114) duration index is still an important parameter in ICR beta variance (delta R2 = 0.354) but equivalent to the emergency index (delta R2 = 0.363).(ABSTRACT TRUNCATED AT 250 WORDS)

Cytokeratin 19 is a subunit of cytokeratin intermediate filament expressed in simple epithelia and their malignant counterparts. Therefore, it is expressed by respiratory epithelium cells and has been detected in lung cancer specimens. An immunoradiometric assay was used to detect a fragment of the cytokeratin 19, referred to as CYFRA 21-1, in the serum of 165 patients with histologically proved lung cancer (128 non-small cell and 37 small cell lung cancers). This prospective study was conducted to evaluate the reliability of this immunoradiometric assay and to identify the relationship between serum CYFRA 21-1 and different features of lung cancer including prognosis. The minimal detectable concentration detected by this assay was 0.06 ng/ml. The reliability of the immunoradiometric assay was demonstrated by the linear relationship between CYFRA 21-1 measurement and dilution of the serum, the reproducibility of the dosage in intraassay and interassay, and the high sensitivity of the method in discriminating low CYFRA 21-1 concentrations. Using a threshold of 3.6 ng/ml, sensitivity and specificity were 0.52 and 0.87, respectively. The sensitivity of the marker was highest in squamous cell carcinoma and lowest in small cell carcinoma. In non-small cell lung cancer patients, the marker varied significantly according to both stage of the disease (Kruskal-Wallis, 13.7; P0.005) and performance status (Kruskal-Wallis, 9.16; P0.05) inasmuch as a high serum CYFRA 21-1 level was associated with advanced stages, mediastinal lymph nodes, and poor performance status. Consequently, the marker was significantly lower in patients who were operated upon when compared with unresectable ones. Lung cancer patients with serum CYFRA 21-1 over 3.6 ng/ml proved to have a significantly shorter overall survival than those with a normal serum level (log rank, P = 0.007; Wilcoxon, P = 0.001). The negative prognostic effect of CYFRA 21-1 was highly significant in squamous cell carcinomas whereas it was nonsignificant for the other histologies. In Cox's model analysis, performance status, stage grouping, and CYFRA 21-1 were the only significant determinants of survival. This study supports the use of the serum fragment of cytokeratin subunit 19 CYFRA 21-1 as an independent prognostic marker of squamous cell carcinoma of the lung.

One hundred and ninety one patients with rheumatoid arthritis were included in an open prospective trial with the aim of evaluating the acceptability, efficacy and therapeutic maintenance levels of methotrexate. The mean treatment duration was 19 +/- 13.2 (3-58) months and the mean weekly dose of methotrexate 10.2 +/- 0.2 mg. Analysis of the 191 patients by intention to treat showed a statistically significant improvement in all clinical parameters as well as a significant fall in sedimentation rate with a corticosteroid-sparing effect. The therapeutic maintenance level of methotrexate was 73% at one year, 65% at 2 years and 46% at 5 years. Adverse reactions occurred in 71 patients (37.1%) including 30 who stopped methotrexate permanently as a result. With cautious and strict patient selection, methotrexate could be used in RA as basic treatment of first choice.

Methods for detection and characterization of episodic fluctuations in circulating hormone levels are frequently used for endocrine investigations, related to the physiological importance of the pulsatile nature of hormone secretion in modulating target-cells response. Several sophisticated methods of pulse analysis have been recently developed and validated, aiming to minimize the false-positive and false-negative error rates. The present report mainly devoted to the clinician aims to analyze and discuss the main features of the most widely used methods for pulse detection.

RESUMO: O objectivo da presente meta-análise foi determinar o valor prognóstico de níveis séricos pré-terapêuticos elevados de Cyfra 21-1, ajustados a co-variáveis clássicas no CPNPC.Baseou-se em elementos registados em bases de dados de estudos controlados (período de 1993 a 2001), publicados e não publicados, apresentados na forma de abstracts ou incluídos em palestras, conferências ou outras apresentações, que tinham como principal end point a determinação do valor prognóstico dos níveis séricos pré-terapêuticos elevados de Cyfra 21-1, cotejados com outras variáveis prognósticas no CPNPC (estádio TNM, PS, e outras) e em que se teve, também, em atenção o tipo de tratamento instituído (cirurgia versus não cirurgia).Foram seleccionadas nove instituições que seguiram 2063 doentes com CPNPC por um período compreendido entre 27 e 78 meses.A sobrevida foi definida como o tempo decorrido entre a data da determinação do valor sérico pré-terapêutico de Cyfra 21-1 até à data da morte do doente. Considerou-se como valor cut-off do mar cador os 3,6 ng/ml; os doentes foram divididos em dois grupos etários, acima e abaixo da mediana de idades, isto é, dos 63 anos.Os elementos colhidos foram analisados estatisticamente utilizando-se o método de Kaplan-Meir para a determinação da distribuição das sobrevidas, enquanto na análise univariada teve-se em conta o teste log-rank e no estudo da regressão multivariada o modelo de Cox.Na série apresentada predominou o sexo masculino (84%), estando 51% dos doentes com um PS de 0-1; 70% dos doentes estavam incluídos no estádio IIIB (27%) ou IV (43%); 50% eram carcinomas epidermóides, só 21% foram submetidos a terapêutica cirúrgica e 49% revelaram valores pré-terapêuticos de Cyfra 21-1 acima de 3,6 ng/ml.Pela análise univariada das sobrevidas, constatou-se que estas foram piores no grupo com Cyfra 21-1 aumentado, sendo outros factores de pior prognóstico o estádio avançado da doença (TNM), o PSâ¥2, e a idade superior a 63 anos; por esta avaliação, os grupos histológicos do tumor e o sexo dos doentes não se revelaram factores de prognóstico.A análise multivariada das sobrevidas de toda a população estudada confirmou o valor pré-terapêutico elevado de Cyfra 21-1 como factor prognóstico negativo, sendo também factores de pior prognóstico o estádio da doença e o PS; aqui, a idade não se mostrou como determinante prognóstico negativo, mas, no grupo acima dos 63 anos, houve a tendência para que tal acontecesse.Por essa mesma análise, observou-se que, nos doentes não cirúrgicos, eram factores de prognóstico negativos a idade, o aumento do valor sérico pré-terapêutico de Cyfra 21-1, o estádio da doença e o PS, enquanto nos doentes cirúrgicos tal não ocorria com a idade e o PS.Em face dos dados apresentados, os autores concluem que a determinação sérica pré-terapêutica dos valores de Cyfra 21-1 é uma variável a considerar na avaliação prognóstica dos doentes com CPNPC, independentemente da terapêutica instituída, existindo concordância entre a presente meta-análise e os dados individuais das diferentes instituições seleccionadas, o que é um forte argumento de que se trata de um verdadeiro determinante prognóstico. COMENTÃRIO: Os factores de prognóstico clássicos incluem o estádio anatómico da doença (TNM), o performance status (PS) e outras condições, como a idade, o sexo, a perda de peso (W) e o(s) local(ais) de metastisação 1.Contudo, os tumores malignos do pulmão apresentam uma grande heterogeneidade no seu comportamento evolutivo, pelo que são necessárias outras variáveis que permitam determinar os casos com pior prognóstico e que, de algum modo, possam influenciar a respectiva programação terapêutica.Das variáveis biológicas, com bem demonstrado valor prognóstico no cancro do pulmão, podem citar-se os níveis séricos elevados de fosfatase alcalina ou de desidrogenase láctica (LDH), a hiperleucocitose ou a hiponatremia 1. Mais recentemente 2, indicam-se também como factores de prognóstico a ploidia, as mutações p53, ou o aumento de expressão da proteína bcl-2, cuja aplicação, na prática clínica, ainda não é rotineira, pela complexidade (e custos) das técnicas envolvidas na sua manipulação, mas sobre os quais recai um interesse sucessivamente crescente pelas implicações que potencialmente acarretam na área dos chamados novos alvos terapêuticos.Dentro da problemática do estudo dos marcadores tumorais séricos, acessíveis na prática clínica diária, tem tomado um lugar de crescente interesse a determinação do valor sérico pré-terapêutico de alguns, como é o caso da citoqueratina Cyfra 21-1, cujo valor, como factor de prognóstico nos CPNPC, tem sido objecto de múltiplos trabalhos, de resultados nem sempre concordantes.Daí o relevo da presente meta-análise, que vem confirmar a importância desse marcador tumoral como determinante prognóstico nos CPNPC.Enquanto as recomendações da American Thoracic Society/European Respiratory Society (ATS/ERS) não indicam qualquer marcador tumoral na avaliação pré-terapêutica dos CPNPC 3, nas recomendações da Société de Pneumologie de Langue Française (SPLF) 4, o Cyfra 21-1 é apontado como tendo valor na avaliação pré-terapêutica deste grupo de tumores, onde revela valor prognóstico independente.Estas afirmações são feitas com base em estudos prospectivos de grupos de doentes, mas questionase o seu interesse clínico, caso a caso, não sendo indicado como factor de prognóstico isolado 4.Por outo lado, numa revisão de 500 trabalhos publicados 5, defende-se que os marcadores tumorais não têm lugar na avaliação prognóstica dos doentes com CPNPC, o que não está de acordo com outros que afirmam que o Cyfra 21-1 se correlaciona bem com o TNM e o PS, constituindo um factor de prognóstico independente, e recomendando-o, mesmo, como uma co-variável a incluir em futuros ensaios clínicos 6.A meta-análise que apresentámos vem reforçar a opinião de que os valores séricos pré-terapêuticos elevados de Cyfra 21-1, nos CPNPC, constituem um factor de prognóstico isolado, independentemente do estádio da doença e da terapêutica instituída, reforçando as conclusões de outro publicado recentemente 7, em que esse marcador tumoral se revelou também nesse grupo de tumores, em estádios IIIB/IV, como um factor de prognóstico, quer isoladamente, quer quando associado a dois outros, o antigénio carcinoembrionário (CEA) e a neuroenolase específica (NSE).Nos doente cirúrgicos, o valor pré-terapêutico elevado de Cyfra 21-1, eventualmente, poderá indicar a necessidade de quimioterapia adjuvante, o que poderá ser mais um argumento a reforçar as conclusões do projecto IALT 8, em que se defende que aquela abordagem terapêutica poderá ser útil, também, nos estádios mais localizados da doença.

BACKGROUND: Alcoholism is a worldwide problem. Many strategies for alcohol detoxification and relapse prevention exist, but each alcohol treatment center has its own program. The objective of this study was to analyze and compare the financial cost and effectiveness of alcohol treatment programs from inpatient stay to follow-up 1 year later. This was a prospective, open, nonrandomized study of 4 specialized alcohol treatment centers and 267 patients admitted for alcohol detoxification. METHODS: We recorded all medical and nonmedical interventions related to the program during patient stay in the hospital and every 3 months after discharge for 1 year and recorded the occurrence of alcohol relapse. Financial evaluation was based on the prices of refund from the French national health insurance service. RESULTS: The mean cost of hospitalization ranged from 1326 euros to 1917 euros(p = 0.001), a variation mainly due to the difference in the length of hospital stay but also to the cost of the inpatient program, routine medical checkups, and drugs administered. The mean cost of 1 year of follow-up per patient ranged from 419 euros to 1704 euros (p = 0.001). The efficiency, corresponding to the money spent to prevent the relapse of one patient during 1 month, was approximately 500 euros/month in three centers and 658 euros in the fourth. However, for a similar efficiency, the effectiveness, assessed by the mean time without relapse, was significantly (p = 0.001) different; center 1, which had the highest total cost, had an effectiveness 1.56 times higher than center 3, which had the lowest cost. CONCLUSIONS: This work emphasizes the heterogeneity of the costs and effectiveness of alcoholism treatment programs and suggests that research should be conducted to determine which program is the most rational, cost-efficient, and beneficial for patients and the public health office economy.