Coexpression of epidermal growth factor receptor with related factors is associated with a poor prognosis in non-small-cell lung cancer

The epidermal growth factor receptor (EGFR) is commonly expressed in non-small-cell lung cancer (NSCLC) and promotes a host of mechanisms involved in tumorigenesis. However, EGFR expression does not reliably predict prognosis or response to EGFR-targeted therapies. The data from two previous studies of a series of 181 consecutive surgically resected stage I-IIIA NSCLC patients who had survived in excess of 60 days were explored. Of these patients, tissue was available for evaluation of EGFR in 179 patients, carbonic anhydrase (CA) IX in 177 patients and matrix metalloproteinase-9 (MMP-9) in 169 patients. We have previously reported an association between EGFR expression and MMP-9 expression. We have also reported that MMP-9 (P=0.001) and perinuclear (p)CA IX (P=0.03) but not EGFR expression were associated with a poor prognosis. Perinuclear CA IX expression was also associated with EGFR expression (P<0.001). Multivariate analysis demonstrated that coexpression of MMP-9 with EGFR conferred a worse prognosis than the expression of MMP-9 alone (P<0.001) and coexpression of EGFR and pCA IX conferred a worse prognosis than pCA IX alone (P=0.05). A model was then developed where the study population was divided into three groups: group 1 had expression of EGFR without coexpression of MMP-9 or pCA IX (number=21); group 2 had no expression of EGFR (number=75); and group 3 had coexpression of EGFR with pCA IX or MMP-9 or both (number=70). Group 3 had a worse prognosis than either groups 1 or 2 (P=0.0003 and 0.027, respectively) and group 1 had a better prognosis than group 2 (P=0.036). These data identify two cohorts of EGFR-positive patients with diametrically opposite prognoses. The group expressing either EGFR and or both MMP-9 and pCA IX may identify a group of patients with activated EGFR, which is of clinical relevance with the advent of EGFR-targeted therapies. © 2004 Cancer Research UK

Canadian guidelines for clinical practice: an analysis of their quality and relevance to the care of adults with comorbidity

<p>Abstract</p> <p>Background</p> <p>Clinical guidelines have been the subject of much criticism in primary care literature partly due to potential conflicts in their implementation among patients with multiple chronic conditions. We assessed the relevance of selected Canadian clinical guidelines on chronic diseases for patients with comorbidity and examined their quality.</p> <p>Methods</p> <p>We selected 16 chronic medical conditions according to their frequency of occurrence, complexity of treatment, and pertinence to primary care. Recent Canadian clinical guidelines (2004 - 2009) on these conditions, published in English or French, were retrieved. We assessed guideline relevance to the care of patients with comorbidity with a tool developed by Boyd and colleagues. Quality was assessed using the Appraisal of Guidelines Research and Evaluation (AGREE) instrument.</p> <p>Results</p> <p>Regarding relevance, 56.2% of guidelines addressed treatment for patients with multiple chronic conditions and 18.8% addressed the issue for older patients. Fifteen guidelines (93.8%) included specific recommendations for patients with one concurrent condition; only three guidelines (18.8%) addressed specific recommendations for patients with two comorbid conditions and one for more than two concurrent comorbid conditions. Quality of the evaluated guidelines was good to very good in four out of the six domains measured using the AGREE instrument. The domains with lower mean scores were Stakeholder Involvement and Applicability.</p> <p>Conclusions</p> <p>The quality of the Canadian guidelines examined is generally good, yet their relevance for patients with two or more chronic conditions is very limited and there is room for improvement in this respect.</p

Experience versus complication rate in third molar surgery

OBJECTIVES: The records of 1087 patients who underwent surgical removal of third molar teeth were prospectively examined to analyse the possible relationship between postoperative complications and the surgeon's experience parameter. METHOD AND MATERIALS: Seven surgeons (three specialists in surgical dentistry [specialists SD] and four oral and maxillofacial Senior House Officers [OMFS residents]) carried out the surgical procedures. For each patient, several variables were recorded including age, gender, radiographic position of extracted teeth, treating surgeon, duration of surgery and postoperative complications. RESULTS: Analysis of the data revealed some differences in the incidence of complications produced by the specialists SD and OMFS residents. The main statistically relevant differences were increase the incidences of trismus, nerve paraesthesia, alveolar osteitis and infection in the resident-treated group, while the specialist-treated group showed higher rates of post-operative bleeding. CONCLUSION: The higher rate of postoperative complications in the resident-treated group suggests that at least some of the complications might be related to surgical experience. Further work needs to compare specialists of training programmes with different years of experience, using large cross – sectional studies

Might Depression, Psychosocial Adversity, and Limited Social Assets Explain Vulnerability to and Resistance against Violent Radicalisation?

BACKGROUND: This study tests whether depression, psychosocial adversity, and limited social assets offer protection or suggest vulnerability to the process of radicalisation. METHODS: A population sample of 608 men and women of Pakistani or Bangladeshi origin, of Muslim heritage, and aged 18-45 were recruited by quota sampling. Radicalisation was measured by 16 questions asking about sympathies for violent protest and terrorism. Cluster analysis of the 16 items generated three groups: most sympathetic (or most vulnerable), most condemning (most resistant), and a large intermediary group that acted as a reference group. Associations were calculated with depression (PHQ9), anxiety (GAD7), poor health, and psychosocial adversity (adverse life events, perceived discrimination, unemployment). We also investigated protective factors such as the number social contacts, social capital (trust, satisfaction, feeling safe), political engagement and religiosity. RESULTS: Those showing the most sympathy for violent protest and terrorism were more likely to report depression (PHQ9 score of 5 or more; RR = 5.43, 1.35 to 21.84) and to report religion to be important (less often said religion was fairly rather than very important; RR = 0.08, 0.01 to 0.48). Resistance to radicalisation measured by condemnation of violent protest and terrorism was associated with larger number of social contacts (per contact: RR = 1.52, 1.26 to 1.83), less social capital (RR = 0.63, 0.50 to 0.80), unavailability for work due to housekeeping or disability (RR = 8.81, 1.06 to 37.46), and not being born in the UK (RR = 0.22, 0.08 to 0.65). CONCLUSIONS: Vulnerability to radicalisation is characterised by depression but resistance to radicalisation shows a different profile of health and psychosocial variables. The paradoxical role of social capital warrants further investigation

Is Violent Radicalisation Associated with Poverty, Migration, Poor Self-Reported Health and Common Mental Disorders?

BACKGROUND: Doctors, lawyers and criminal justice agencies need methods to assess vulnerability to violent radicalization. In synergy, public health interventions aim to prevent the emergence of risk behaviours as well as prevent and treat new illness events. This paper describes a new method of assessing vulnerability to violent radicalization, and then investigates the role of previously reported causes, including poor self-reported health, anxiety and depression, adverse life events, poverty, and migration and socio-political factors. The aim is to identify foci for preventive intervention. METHODS: A cross-sectional survey of a representative population sample of men and women aged 18-45, of Muslim heritage and recruited by quota sampling by age, gender, working status, in two English cities. The main outcomes include self-reported health, symptoms of anxiety and depression (common mental disorders), and vulnerability to violent radicalization assessed by sympathies for violent protest and terrorist acts. RESULTS: 2.4% of people showed some sympathy for violent protest and terrorist acts. Sympathy was more likely to be articulated by the under 20s, those in full time education rather than employment, those born in the UK, those speaking English at home, and high earners (>£75,000 a year). People with poor self-reported health were less likely to show sympathies for violent protest and terrorism. Anxiety and depressive symptoms, adverse life events and socio-political attitudes showed no associations. CONCLUSIONS: Sympathies for violent protest and terrorism were uncommon among men and women, aged 18-45, of Muslim heritage living in two English cities. Youth, wealth, and being in education rather than employment were risk factors

The care of older cancer patients in the United Kingdom

The ageing population poses new challenges globally. Cancer care for older patients is one of these challenges, and it has a significant impact on societies. In the United Kingdom (UK), as the number of older cancer patients increases, the management of this group has become part of daily practice for most oncology teams in every geographical area. Older cancer patients are at a higher risk of both under- and over-treatment. Therefore, the assessment of a patient’s biological age and effective organ functional reserve becomes paramount. This may then guide treatment decisions by better estimating a prognosis and the risk-to-benefit ratio of a given therapy to anticipate and mitigate against potential toxicities/difficulties. Moreover, older cancer patients are often affected by geriatric syndromes and other issues that impact their overall health, function and quality of life. Comprehensive geriatric assessments offer an opportunity to identify and address health problems which may then optimise one’s fitness and well-being. Whilst it is widely accepted that older cancer patients may benefit from such an approach, resources are often scarce, and access to dedicated services and research remains limited to specific centres across the UK. The aim of this project is to map the current services and projects in the UK to learn from each other and shape the future direction of care of older patients with cancer

Hypoxia-regulated carbonic anhydrase IX expression is associated with poor survival in patients with invasive breast cancer.

Tumour hypoxia is a microenvironmental factor related to poor response to radiation, chemotherapy, genetic instability, selection for resistance to apoptosis, and increased risk of invasion and metastasis. Hypoxia-regulated carbonic anhydrase IX (CA IX) has been studied in various tumour sites and its expression has been correlated with the clinical outcome. The purpose of this study was to investigate the correlation of CA IX expression with outcome in patients with invasive breast cancer. We conducted a retrospective study examining the effects of carbonic anhydrase IX (CA IX) on survival in patients with breast cancer. To facilitate the screening of multiple tissue blocks from each patient, tissue microarrays were prepared containing between two and five representative samples of tumour per patient. Immunohistochemistry was used to examine expression of CA IX in patients with breast cancer. The study includes a cohort of 144 unselected patients with early invasive breast cancer who underwent surgery, and had CA IX expression and follow-up data available for analysis. At the time of analysis, there were 28 deaths and median follow-up of 48 months with 96% of patients having at least 2 years of follow-up. CA IX was negative for 107 patients (17 deaths) and positive for 37 patients (11 deaths). Kaplan-Meier survival curves show that survival was superior in the CA IX-negative group with a 2-year survival of 97% for negatives and 83% for positives (log-rank test P=0.01). Allowing for potential prognostic variables in a Cox regression analysis, CA IX remained a significant independent predictor of survival (P=0.035). This study showed in both univariate and multivariate analysis that survival is significantly inferior in patients with tumour expressing CA IX. Prospective studies are underway to investigate this correlation in clinical trial setting