The role of cancer related inflammation, Src family kinases and matrix metalloproteinase 9 in colorectal cancer

Colorectal cancer (CRC) is the third most common cancer in the UK with 41,000 new cases diagnosed in 2011. Despite undergoing potentially curative resection, a significant amount of patients develop recurrence. Biomarkers that aid prognostication or identify patients who are suitable for adjuvant treatments are needed. The TNM staging system does a reasonably good job at offering prognostic information to the treating clinician, but it could be better and identifying methods of improving its accuracy are needed. Tumour progression is based on a complex relationship between tumour behaviour and the hosts’ inflammatory responses. Sustained tumour cell proliferation, evading growth suppressors, resisting apoptosis, replicative immortality, sustained angiogenesis, invasion & metastasis, avoiding immune destruction, deregulated cellular energetics, tumour promoting inflammation and genomic instability & mutation have been identified as hallmarks. These hallmarks are malignant behaviors are what makes the cell cancerous and the more extreme the behaviour the more aggressive the cancer the more likely the risk of a poor outcome. There are two primary genomic instability pathways: Microsatellite Instability (MSI) and Chromosomal Instability (CI) also referred to as Microsatellite Stability (MSS). Tumours arising by these pathways have a predilection for specific anatomical, histological and molecular biological features. It is possible that aberrant molecular expression of genes/proteins that promote malignant behaviors may also act as prognostic and predictive biomarkers, which may offer superior prognostic information to classical prognostic features. Cancer related inflammation has been described as a 7th hallmark of cancer. Despite the systemic inflammatory response (SIR) being associated with more aggressive malignant disease, infiltration by immune cells, particularly CD8+ lymphocytes, at the advancing edge of the tumour have been associated with improved outcome and tumour MSI. It remains unknown if the SIR is associated with tumour MSI and this requires further study. The mechanisms by which colorectal cancer cells locally invade through the bowel remain uncertain, but connective tissue degradation by matrix metalloproteinases (MMPs) such as MMP-9 have been implicated. MMP-9 has been found in the cancer cells, stromal cells and patient circulation. Although tumoural MMP-9 has been associated with poor survival, reports are conflicting and contain relatively small sample sizes. Furthermore, the influence of high serum MMP-9 on survival remains unknown. Src family kinases (SFKs) have been implicated in many adverse cancer cell behaviors. SFKs comprise 9 family members BLK, C-SRC, FGR, FYN, HCK, LCK, LYN, YES, YRK. C-SRC has been the most investigated of all SFKs, but the role of other SFKs in cellular behaviors and their prognostic value remains largely unknown. The development of Src inhibitors, such as Dasatinib, has identified SFKs as a potential therapeutic target for patients at higher risk of poor survival. Unfortunately, clinical trials so far have not been promising but this may reflect inadequate patient selection and SFKs may act as useful prognostic and predictive biomarkers. In chapter 3, the association between cancer related inflammation, tumour MSI, clinicopathological factors and survival was tested in two independent cohorts. A training cohort consisting of n=182 patients and a validation cohort of n=677 patients. MSI tumours were associated with a raised CRP (p=0.003). Hypoalbuminaemia was independently associated with poor overall survival in TNM stage II cancer (HR 3.04 (95% CI 1.44 – 6.43);p=0.004), poor recurrence free survival in TNM stage III cancer (HR 1.86 (95% 1.03 – 3.36);p=0.040) and poor overall survival in CI colorectal cancer (HR 1.49 (95% CI 1.06 – 2.10);p=0.022). Interestingly, MSI tumours were associated with poor overall survival in TNM stage III cancer (HR 2.20 (95% CI 1.10 – 4.37);p=0.025). In chapter 4, the role of MMP-9 in colorectal cancer progression and survival was examined. MMP-9 in the tissue was assessed using IHC and serum expression quantified using ELISA. Serum MMP-9 was associated with cancer cell expression (Spearman’s Correlation Coefficient (SCC) 0.393, p<0.001)) and stromal expression (SCC 0.319, p=0.002). Serum MMP-9 was associated with poor recurrence-free (HR 3.37 (95% CI 1.20 – 9.48);p=0.021) and overall survival (HR 3.16 (95% CI 1.22 – 8.15);p=0.018), but tumour MMP-9 was not survival or MSI status. In chapter 5, the role of SFK expression and activation in colorectal cancer progression and survival was studied. On PCR analysis, although LYN, C-SRC and YES were the most highly expressed, FGR and HCK had higher expression profiles as tumours progressed. Using IHC, raised cytoplasmic FAK (tyr 861) was independently associated with poor recurrence free survival in all cancers (HR 1.48 (95% CI 1.02 – 2.16);p=0.040) and CI cancers (HR 1.50 (95% CI 1.02 – 2.21);p=0.040). However, raised cytoplasmic HCK (HR 2.04 (95% CI 1.11 – 3.76);p=0.022) was independently associated with poor recurrence-free survival in TNM stage II cancers. T84 and HT29 cell lines were used to examine the cellular effects of Dasatinib. Cell viability was assessed using WST-1 assay and apoptosis assessed using an ELISA cell death detection assay. Dasatinib increased T84 tumour cell apoptosis in a dose dependent manner and resulted in reduced expression of nuclear (p=0.008) and cytoplasmic (p=0.016) FAK (tyr 861) expression and increased nuclear FGR expression (p=0.004). The results of this thesis confirm that colorectal cancer is a complex disease that represents several subtypes of cancer based on molecular biological behaviors. This thesis concentrated on features of the disease related to inflammation in terms of genetic and molecular characterisation. MSI cancers are closely associated with systemic inflammation but despite this observation, they retain their relatively improved survival. MMP-9 is a feature of tissue remodeling during inflammation and is also associated with degradation of connective tissue, advanced T-stage and poor outcome when measured in the serum. The lack of stromal quantification due to TMA use rather than full sections makes the value of tumoural MMP-9 immunoreactivity in the prognostication and its association with MSI unknown and requires further study. Finally, SFK activation was also associated with SIR, however, only cytoplasmic HCK was independently associated with poor survival in patients with TNM stage II disease, the group of patients where identifying a novel biomarker is most needed. There is still some way to go before these biomarkers are translated into clinical practice and future work needs to focus on obtaining a reliable and robust scientific technique with validation in an adequately powered independent cohort.

Mercadeo farmacéutico de productos bajo prescripción: efectos de las estrategias Direct-to-Consumer-Advertising en el comportamiento de los consumidores y de prescripción de los médicos

Este proyecto se origina en el interés de analizar las estrategias actuales de promoción de productos farmacéuticos, en el marco del debate sobre el efecto persuasivo o informativo que la publicidad directa tiene sobre los consumidores. El objetivo es determinar el efecto de las estrategias de promoción directa para consumidores (Direct to Consumer Advertising [DTCA]) sobre el comportamiento de compra de pacientes y las prescripciones que formulan los médicos en el mercado de productos bajo receta en Estados Unidos. Para tal fin se propuso realizar una monografía que incluyera una revisión de literatura de carácter argumentativo, consultando información de nivel secundario en bases de datos científicas cuyos contenidos obedecieran a criterios metodológicos determinados por la naturaleza argumentativa del estudio. Adicionalmente, se analizó el debate sobre estos anuncios a la luz de dos estudios realizados a pacientes con cáncer de seno, próstata y colon, liderados por el Pennsylvania Cancer Registry con los productos biofarmacéuticos Avodart® y Flomax®. Finalmente, la investigación se fundamentó en la relación del mercado farmacéutico en Estados Unidos con cada uno de los agentes que interactúan en él; consumidores, médicos prescriptores y empresas farmacéuticas, así como el valor que estos comparten través de dichas interacciones. Se concluye que el comportamiento de compra de los consumidores está determinado por la naturaleza de la patología que padecen y el comportamiento de los profesionales que prescriben a sus pacientes se ve influenciado por los anuncios DTCA.

Barreiras e facilitadores à prática do acompanhamento farmacoterapêutico nos serviços farmacêuticos hospitalares portugueses

Objectivos: Identificar e compreender as barreiras e os facilitadores à prática do Acompanhamento Farmacoterapêutico (AFT) nos serviços farmacêuticos hospitalares portugueses. Método: Estudo qualitativo mediante realização de entrevistas semi-estruturadas a farmacêuticos hospitalares com e sem experiência no AFT e análise de conteúdo, retroactiva e temática. Resultados: Estrutura dos serviços farmacêuticos: barreiras (1) falta de tempo, organização das actividades orientadas para a logística, instabilidade dos recursos humanos, barreiras físicas à comunicação, relações em divergência; facilitadores (2) reestruturação, trabalho em equipa. Farmacêutico: (1) resistência à mudança, qualificação inadequada; (2) atitude positiva, legitimação, formação. Meio externo: (1) falta de apoio institucional, relacionamento com o doente, o médico e farmacêutico comunitário, ensino inadequado; (2) apoio institucional, procura do doente, cooperação com o médico e o farmacêutico comunitário, ensino adequado. Tecnologia: (1) acesso aos dados clínicos e a informação, método inadequado; (2) acesso à informação, método adequado, documentação, informatização, marketing, boas práticas. Conclusão: As entrevistas semi-estruturadas fornecerem uma visão ampla, detalhada e pragmática dos potenciais determinantes de uma prática generalizada do AFT nos serviços farmacêuticos hospitalares portugueses. /ABSTRACT: Objectives: To identify and understand the barriers and facilitators for the practice of Medication Therapy Management (MTM) in portuguese’s hospital pharmacy. Method: Qualitative study trough semi-structured interviews with MTM experienced and inexperienced hospital pharmacists followed by retroactive content and thematic analysis. Results: Structure of hospital pharmacy: barriers (1) lack of time, activities focused on logistics, instability of human resources, physical barriers to communication, divergent relationships; facilitators (2) restructuring, teamwork. Pharmacist: (1) resistance to change, inadequate skills, (2) positive attitude, legitimating, formation. Environment: (1) lack of institutional support, relationship with patient, physician and community pharmacist, inadequate teaching, (2) institutional support, patient's demand, cooperation with physician and community pharmacist, appropriate teaching. Technology: (1) lack of access to clinical data and information, inadequate method, (2) access to information, appropriate method, documentation, computerization, marketing, good pharmacy practices. Conclusion: The semi-structured interviews provide a broad, comprehensive and pragmatic view of potential determinants for wide practice of MTM in Portuguese’s hospital pharmacy.

Information Usefulness To Support Dialogue Management in Healthcare

The main objective of the framework we are proposing is to help the physician obtain information about the patient's condition in order to reach the \emph{correct} diagnosis as soon as possible. In our proposal, the number of interactions between the physician and the patient is reduced to a strict minimum on the one hand and, on the other hand, it is made possible to increase the number of questions to be asked if the uncertainty about the diagnosis persists. These advantages are due to the fact that (i) we implement a reasoning component that allows us to predict a symptom from another symptom without explicitly asking the patient, (ii) we consider non-binary values for the weights associated with the symptoms, we introduce a dataset filtering process in order to choose which partition should be used with respect to some particular characteristics of the patient, and, in addition, (iv) it was added new functionality to the framework: the ability to detect further future risks of a patient already knowing his pathology. The experimental results we obtained are very encouraging

Timeliness, efficiency and public procurement in hip surgery in Italy

Considering different perspectives, the scope of this thesis is to investigate how to improve healthcare resources allocation and the provision efficiency for hip surgeries, a resource-intensive operation, among the most frequently performed on the elderly, with a trend in volume that is increasing in years due to population aging. Firstly, the effect of Time-To-Surgery (TTS) on mortality for hip fracture patients is investigated. The analysis attempts to account for TTS endogeneity due to the inability to fully control for variables affecting patient delay – e.g. patient severity. Exploiting an instrumental variable model, where being admitted on Friday or Saturday predicts longer TTS, findings show exogenous TTS does not have a significant effect on mortality. Thus suggesting surgeons prioritize patients effectively, neutralizing the adverse impact of longer TTS. Then, the volume-outcome relation for total hip replacement surgery is analyzed, seeking to account for selective referral, which may be present in elective surgery context, and induce reverse causality issue in the volume-outcome relation. The analysis employs a conditional choice model where patient travel distance from all regions' hospitals is used as a hospital choice predictor. Findings show the exogenous hospital volume significantly decreases adverse outcomes probability, especially in the short run. Finally, the change in public procurement design enforced in the Romagna LHA (Italy) is exploited to assess its impact on hip prostheses cost, surgeons' implant choice, and patient health outcomes. Hip prostheses are the major cost-driver of hip replacement surgeries, hence it is crucial to design the public tender such that implant prices are minimized, but cost-containment policies have to be weighted with patient well-being. Evidence shows that a cost reduction occurred without a significant surgeons’ choices impact. Positive or no effect of surgeons specialization is found on patients outcomes after the new procurement introduction.

Value Of Sentinel Lymph Node Biopsy In Papillary Thyroid Cancer: Initial Results Of A Prospective Trial.

The objectives of the study were to evaluate the performance of sentinel lymph node biopsy (SLNB) in detecting occult metastases in papillary thyroid carcinoma (PTC) and to correlate their presence to tumor and patient characteristics. Twenty-three clinically node-negative PTC patients (21 females, mean age 48.4 years) were prospectively enrolled. Patients were submitted to sentinel lymph node (SLN) lymphoscintigraphy prior to total thyroidectomy. Ultrasound-guided peritumoral injections of (99m)Tc-phytate (7.4 MBq) were performed. Cervical single-photon emission computed tomography and computed tomography (SPECT/CT) images were acquired 15 min after radiotracer injection and 2 h prior to surgery. Intra-operatively, SLNs were located with a gamma probe and removed along with non-SLNs located in the same neck compartment. Papillary thyroid carcinoma, SLNs and non-SLNs were submitted to histopathology analysis. Sentinel lymph nodes were located in levels: II in 34.7 % of patients; III in 26 %; IV in 30.4 %; V in 4.3 %; VI in 82.6 % and VII in 4.3 %. Metastases in the SLN were noted in seven patients (30.4 %), in non-SLN in three patients (13.1 %), and in the lateral compartments in 20 % of patients. There were significant associations between lymph node (LN) metastases and the presence of angio-lymphatic invasion (p = 0.04), extra-thyroid extension (p = 0.03) and tumor size (p = 0.003). No correlations were noted among LN metastases and patient age, gender, stimulated thyroglobulin levels, positive surgical margins, aggressive histology and multifocal lesions. Sentinel lymph node biopsy can detect occult metastases in PTC. The risk of a metastatic SLN was associated with extra-thyroid extension, larger tumors and angio-lymphatic invasion. This may help guide future neck dissection, patient surveillance and radioiodine therapy doses.

Levotiroxina e o problema da permutabilidade de drogas de estreito intervalo terapêutico

The exchange of a prescribed drug by other similar, by generic products and even by custom products has become common practice in our country, often ignoring basic tenets of bioequivalence, interchangeability, stability and characteristics of the pharmaceutical compounds. In the case of drugs of narrow therapeutic index, such as levothyroxine, these problems are intensified, putting the effectiveness of treatment and patient health at serious risk. We review the pertinent legislation, emphasizing the characteristics of levothyroxine and adverse effects that limit the interchangeability of the compound.

Termo de consentimento livre e esclarecido aos usuários de clínicas odontológicas brasileiras: aspectos éticos e legais

O consentimento do paciente antes do início de qualquer procedimento é uma condição a ser respeitada pelos profissionais da odontologia, sem nenhuma exceção. É necessário que o paciente esteja ciente de seu status de saúde, de suas necessidades específicas, do propósito de cada tratamento, conheça os planejamentos alternativos (incluindo o não tratamento), saiba do seu prognóstico, riscos, consequências, limitações e se conscientize das suas responsabilidades e as do seu cirurgião-dentista, proporcionando o sucesso do tratamento. O termo de consentimento livre e esclarecido (TCLE) visa fortalecer e esclarecer a posição do paciente, estabelecendo os direitos e deveres de ambas as partes paciente e profissional. O conhecimento integral do tratamento diminuirá a ansiedade do paciente e as complicações de tratamento, promoverá maior qualidade dos serviços odontológicos e maior satisfação do dentista e do paciente. Entretanto, no Brasil, poucos artigos são encontrados e existem alguns problemas éticos envolvendo as clínicas odontológicas, no que diz respeito a este documento de esclarecimento para o paciente. Diante disso, este trabalho tem por objetivo realizar uma revisão crítica sobre o tema abordado, demonstrando a importância do TCLE na clínica odontológica brasileira e na vida profissional dos cirurgiões-dentistas.

Atenção farmacêutica em farmácias e drogarias: existe um processo de mudança?

Para se conhecer a prática profissional de farmacêuticos que atuam em farmácias e drogarias, seus conhecimentos e percepções acerca da Atenção Farmacêutica (AF), realizou-se estudo descritivo com 91 farmacêuticos do município de Jundiaí-SP. A maioria era jovem (62,6% entre 20 e 29 anos), do sexo feminino (63,7%), graduada em instituições privadas (90,1%) e não proprietária do estabelecimento (87,9%). Desenvolviam atividades administrativas, técnicas e de atenção ao usuário, principalmente dispensação de medicamentos e orientação; 67,0% acompanhavam o tratamento farmacoterapêutico dos usuários, mas sem registrar informações. Para 62,7%, AF relacionava-se apenas à orientação e atendimento dispensados, mas tais atividades não eram realizadas de forma sistemática e organizada, como preconizado. Muitos (91,2%) consideravam necessário realizar trabalho mais intenso com os usuários, porém apontaram dificuldades como falta de tempo e de apoio dos proprietários e desinteresse dos usuários. Várias dessas dificuldades têm sido verificadas também em outros países, sugerindo que a prática da AF: (a) requer uma mudança estrutural e rearranjo de funções, uma vez que, atualmente, a estrutura e as atividades são adequadas à atividade comercial; (b) reflete uma crise de identidade profissional e, em consequência, falta de reconhecimento social e pouca inserção na equipe multiprofissional de saúde. O conhecimento sobre AF mostrou-se limitado, mas a situação pode vir a alterar-se à medida que as mudanças curriculares em curso surtam efeito na formação dos novos farmacêuticos.

A importância da intervenção nutricional na redução do peso corpóreo em pacientes com síndrome do anticorpo antifosfolípide

OBJETIVO: Avaliar a eficácia da intervenção nutricional na redução do excesso de peso (EP), em pacientes com síndrome do anticorpo antifosfolípide (SAF). MÉTODO: Incluídos 40 pacientes, acima de 18 anos, com diagnóstico de SAF primária ou secundária, acompanhados no Serviço de Reumatologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP) e recrutados no período de outubro de 2005 a fevereiro de 2006. Foram coletados dados demográficos e realizados a revisão de prontuários, a mensuração de peso e da altura, o cálculo do índice de massa corpórea (IMC) atual e a adequação da dieta pelo IMC ideal. Foi realizada avaliação na primeira consulta e após intervalo mínimo de dois meses. RESULTADOS: A média de idade dos pacientes foi de 41 anos, sendo 93% de mulheres. Os pacientes com SAF primária perfaziam 25%, com média de dois anos da doença. A trombose venosa ocorreu em 63%, arterial em 48% e manifestações obstétricas em 27%. Na primeira consulta, 68% apresentavam EP, 27% eram eutróficos e 5% estavam com baixo peso (BP). Após três meses de intervenção, os eutróficos mantiveram o peso e os de BP tornaram-se eutróficos, segundo o IMC. Interessantemente, entre os pacientes com EP (n = 27), 82% emagreceram, 14% engordaram e 4% se mantiveram. Especificamente, 11 pacientes apresentaram 1% a 3% de perda ponderal de peso, oito perderam de 4% a 7%, dois reduziram 8% a 9% e um reduziu 13,6% com o acompanhamento nutricional. CONCLUSÃO: Foi demonstrado no presente estudo que a intervenção nutricional conseguiu atingir metas para redução de peso, possibilitando diminuição no risco trombótico num curto período, sendo, portanto, uma modalidade terapêutica inicial e de eleição para corrigir o EP em pacientes com SAF.

Health services performance for TB treatment in Brazil: a cross-sectional study

Background: Researches to evaluate Primary Health Care performance in TB control in Brazil show that different cities aggregate local specificities in the dynamics of coping with the disease. This study aims to evaluate health services' performance in TB treatment in cities across different Brazilian regions. Methods: This cross-sectional study was conducted in five cities that are considered priorities for TB control in Brazil: Itaborai (ITA), Ribeirao Preto (RP) and Sao Jose do Rio Preto (SJRP) in the Southeast; Campina Grande (CG) and Feira de Santana (FS) in the Northeast. Data were collected through interviews with 514 TB patients under treatment in 2007, using the Primary Care Assessment Tool adapted for TB care in Brazil. Indicators were constructed based on the mean response scores (Likert scale) and compared among the study sites. Results: ""Access to treatment"" was evaluated as satisfactory in the Southeast and regular in the Northeast, which displayed poor results on 'home visits' and 'distance between treatment site and patient's house'. ""Bond"" was assessed as satisfactory in all cities, with a slightly better performance in RP and SJRP. ""Range of services"" was rated as regular, with better performance of southeastern cities. 'Health education', 'DOT' and 'food vouchers' were less offered in the Northeast. ""Coordination"" was evaluated as satisfactory in all cities. ""Family focus"" was evaluated as satisfactory in RP and SJRP, and regular in the others. 'Professional asking patient's family about other health problems' was evaluated as unsatisfactory, except in RP. Conclusions: Two types of obstacles are faced for health service performance in TB treatment in the cities under analysis, mainly in the Northeast. The first is structural and derives from difficulties to access health services and actions. The second is organizational and derives from the way health technologies and services are distributed and integrated. Incentives to improve care organization and management practices, aimed at the integration of primary, secondary and tertiary services, can contribute towards a better performance of health services in TB treatment.

Como implementar uma diretriz - da teoria à prática: exemplo da profilaxia para Tromboembolismo Venoso

The objective of this manuscript is to discuss the existing barriers for the dissemination of medical guidelines, and to present strategies that facilitate the adaptation of the recommendations into clinical practice. The literature shows that it usually takes several years until new scientific evidence is adopted in current practice, even when there is obvious impact in patients' morbidity and mortality. There are some examples where more than thirty years have elapsed since the first case reports about the use of a effective therapy were published until its utilization became routine. That is the case of fibrinolysis for the treatment of acute myocardial infarction. Some of the main barriers for the implementation of new recommendations are: the lack of knowledge of a new guideline, personal resistance to changes, uncertainty about the efficacy of the proposed recommendation, fear of potential side-effects, difficulties in remembering the recommendations, inexistence of institutional policies reinforcing the recommendation and even economical restrains. In order to overcome these barriers a strategy that involves a program with multiple tools is always the best. That must include the implementation of easy-to-use algorithms, continuous medical education materials and lectures, electronic or paper alerts, tools to facilitate evaluation and prescription, and periodic audits to show results to the practitioners involved in the process. It is also fundamental that the medical societies involved with the specific medical issue support the program for its scientific and ethical soundness. The creation of multidisciplinary committees in each institution and the inclusion of opinion leaders that have pro-active and lasting attitudes are the key-points for the program's success. In this manuscript we use as an example the implementation of a guideline for venous thromboembolism prophylaxis, but the concepts described here can be easily applied to any other guideline. Therefore, these concepts could be very useful for institutions and services that aim at quality improvement of patient care. Changes in current medical practice recommended by guidelines may take some time. However, if there is a broader participation of opinion leaders and the use of several tools listed here, they surely have a greater probability of reaching the main objectives: improvement in provided medical care and patient safety.

Laparoscopic nephrectomy outside gerota fascia for management of inflammatory kidney

Background and Purpose: A nonfunctioning inflammatory kidney is a challenging surgical condition for urologists. Some investigators recommend open surgery because of the surgical difficulties caused by the inflammatory process, whereas others try to apply the advantages of a ""simple"" non-hand-assisted laparoscopic approach. We report our experience with simple laparoscopic nephrectomy for inflammatory kidney management. Patients and Methods: From July 2002 through December 2006, 50 pure laparoscopic nephrectomies were performed for inflammatory kidney ( 43 because of pyelonephritis, 5 for xanthogranulomatous pyelonephritis (XGP), and 2 for pyonephrosis). Histopathologic analysis was the criterion used for inflammatory kidney diagnosis. Pain or recurrent urinary tract infection associated with a nonfunctioning excluded kidney was the eligibility criterion for the procedure. Preoperatively, all patients underwent complete image and functional renal assessment. Morcellation was used to remove surgical specimens. Conversion index, surgical difficulties, operative time, and postoperative complications were evaluated. Results: Conversion was performed in 14 of 50 (28%) patients, including two with XGP and one with pyonephrosis. Adhesions, vascular (two inferior vena cava) lesions, and intestinal lesions (two colon) were the main causes of conversion. Acute pancreatitis developed in one patient, and one patient had a wound infection. Reoperations were unnecessary, and no deaths occurred. Conclusion: Pure laparoscopic nephrectomy was successful in 72% of patients with inflammatory kidneys. The laparoscopic dissection was useful even in those cases converted to open surgery. This is a high-risk procedure, however, and both surgeon and patient must be aware of that before the decision is made for this approach.

Decision theory applied to image quality control in radiology

Background: The present work aims at the application of the decision theory to radiological image quality control ( QC) in diagnostic routine. The main problem addressed in the framework of decision theory is to accept or reject a film lot of a radiology service. The probability of each decision of a determined set of variables was obtained from the selected films. Methods: Based on a radiology service routine a decision probability function was determined for each considered group of combination characteristics. These characteristics were related to the film quality control. These parameters were also framed in a set of 8 possibilities, resulting in 256 possible decision rules. In order to determine a general utility application function to access the decision risk, we have used a simple unique parameter called r. The payoffs chosen were: diagnostic's result (correct/incorrect), cost (high/low), and patient satisfaction (yes/no) resulting in eight possible combinations. Results: Depending on the value of r, more or less risk will occur related to the decision-making. The utility function was evaluated in order to determine the probability of a decision. The decision was made with patients or administrators' opinions from a radiology service center. Conclusion: The model is a formal quantitative approach to make a decision related to the medical imaging quality, providing an instrument to discriminate what is really necessary to accept or reject a film or a film lot. The method presented herein can help to access the risk level of an incorrect radiological diagnosis decision.

Work disability remains a major problem in rheumatoid arthritis in the 2000s: data from 32 countries in the QUEST-RA Study

Introduction: Work disability is a major consequence of rheumatoid arthritis (RA), associated not only with traditional disease activity variables, but also more significantly with demographic, functional, occupational, and societal variables. Recent reports suggest that the use of biologic agents offers potential for reduced work disability rates, but the conclusions are based on surrogate disease activity measures derived from studies primarily from Western countries. Methods: The Quantitative Standard Monitoring of Patients with RA (QUEST-RA) multinational database of 8,039 patients in 86 sites in 32 countries, 16 with high gross domestic product (GDP) (>24K US dollars (USD) per capita) and 16 low-GDP countries (<11K USD), was analyzed for work and disability status at onset and over the course of RA and clinical status of patients who continued working or had stopped working in high-GDP versus low-GDP countries according to all RA Core Data Set measures. Associations of work disability status with RA Core Data Set variables and indices were analyzed using descriptive statistics and regression analyses. Results: At the time of first symptoms, 86% of men (range 57%-100% among countries) and 64% (19%-87%) of women <65 years were working. More than one third (37%) of these patients reported subsequent work disability because of RA. Among 1,756 patients whose symptoms had begun during the 2000s, the probabilities of continuing to work were 80% (95% confidence interval (CI) 78%-82%) at 2 years and 68% (95% CI 65%-71%) at 5 years, with similar patterns in high-GDP and low-GDP countries. Patients who continued working versus stopped working had significantly better clinical status for all clinical status measures and patient self-report scores, with similar patterns in high-GDP and low-GDP countries. However, patients who had stopped working in high-GDP countries had better clinical status than patients who continued working in low-GDP countries. The most significant identifier of work disability in all subgroups was Health Assessment Questionnaire (HAQ) functional disability score. Conclusions: Work disability rates remain high among people with RA during this millennium. In low-GDP countries, people remain working with high levels of disability and disease activity. Cultural and economic differences between societies affect work disability as an outcome measure for RA.