Measurement of community beliefs about colorectal cancer

Few educational campaigns have focused on bowel cancer, though studies have indicated that members of the community need and want current information about relevant issues. In order to facilitate research in this area, reliable and valid measures of community attitudes are needed. Content validity of a survey instrument was obtained through use of a Delphi process with Directors of Education from the Australia Cancer Council and focus group discussions with informed members of the public. The subsequent survey of community perceptions about colorectal cancer included a broad range of content areas related to the risk of bowel cancer, preventing and coping with bowel cancer and beliefs about susceptibility and severity. The construct validity of these content areas was investigated by use of a factor analysis and confirmation of an association with related predictor variables. Two measures related to personal influence and anticipated coping responses showed favourable psychometric properties, including moderate to high levels of internal consistency and test-retest reliability. A test of the concurrent validity of these measures requires further development of instruments related to colorectal cancer or adaptation of measures from other areas of health research. (C) 2000 Elsevier Science Ltd. All rights reserved.

The source, cost and prevention of central venous catheter-related infection

Central venous catheters have become an integral part of patient management however they are associated with many complications including infection. Despite efforts being made to reduce the incidence of such infect ions the problem continues to increase and has resource implications for the Health Service. Studies relating to the source of microorganisms causing CVC-associated infection, the cost of such infections and the efficacy of an antimicrobial catheter have been undertaken. Thirty patients who required a CVC as part of their medical management and underwent cardiac surgery had the distal tips of their catheters sampled whilst in situ. Sampling took place within 1 h of catheter placement. Bacteria were isolated from 16% of the catheter distal tips sampled in situ. The guidewires used to insert the devices were also contaminated (50%). When CVC were inserted via a protective sheath, avoiding contact with the skin. the incidence of microbial contamination was reduced. These findings suggest that despite rigorous skin disinfection and strict aseptic technique, viable microorganisms are impacted onto the distal tip of CVC during the insertion procedure. Needleless intravascular access devices have been introduced in order to reduce the incidence of need1estick injury. However, it was unclear whether such connectors would act as a portal of entry for microorganisms to CVC. The efficacy of these devices was investigated. Within the controlled laboratory environment it was demonstrated that needleless devices, when challenged with microorganisms, did not allow the passage of microbes when flu id was injected. This therefore suggested that the devices should not increase the risk of catheter colonisation. When used in clinical practice however microbial contamination of the needleless connectors was 55 % in comparison to the routinely used luer connectors (23%). The cost of infections associated with CVC was determined. Twenty patients catheterised with a CVC designed for long term use who were admitted to hospital with a presumptive diagnosis of catheter-related infection were studied. The treatment given specifically for this infection was costed. The mean cost of such an infection was £ 1781.81. Throughout the UK this may amount to £1.565.906 per annum. The cost of infections associated with CVC designed for short term use was estimated to be between 5 and 7 million pounds per annum in the UK. In an attempt to reduce both the incidence and cost of catheter- related infection antimicrobial CVC have been developed. The efficacy of a novel polyurethane CVC impregnated on both the internal and external catheter surface with the quaternary ammonium compound benzalkonium chloride was investigated. Eighty eight patients received an antimicrobial catheter and 78 patients a conventional polyurethane CVC. The anti-microbial CVC resulted in a reduction in microbial colonisation of the external and internal polymer surfaces as compared to the control device. The observed reduction in microbial colonisation with the anti-microbial CVC may decrease the likelihood of subsequent infection offering a useful approach to the prevention of catheter-related infections.

The prevention and diagnosis of central venous catheter-related infection

The potential source of CVC colonisation was assessed. Isolates of coagulase-negative staphylococci (CoNS) recovered from the skin and CVC components of 3 cardiothoracic surgery patients were characterised by pulsed-field gel electrophoresis (PFGE). The genetic heterogeneity of CoNS isolated from the skin was demonstrated and specific genotypes implicated in catheter colonisation. In addition, phenotypic and genotypic typing techniques were assessed for their ability to characterise strains of CoNS recovered from 33 patients who developed catheter-related bloodstream infection (CR-BSI) on a bone marrow transplant (BMT) unit and Siaphylococcus aureus recovered from 6 cardiothoracic surgery patients with surgical site infection (SSI) following median sternotomy. This epidemiological investigation revealed that common strains of CoNS and 51 aureus where not associated with infection in patients with CR-BSI or sternal SSI during the study period. Furthermore, there was no correlation between phenotypic and genotypic characterisation results. The variable expression of phenotypic traits within strains of staphylococci was evident whilst PFGE and randomly amplified polymorphic DNA (RAPD) were highly discriminatory for the molecular characterisation of S. aureus and CoNS. This was highlighted in 8 stem cell transplant (SCT) patients whereby it was demonstrated that routine identification and characterisation of CoNS by phenotypic techniques may not be adequate for the diagnosis of CR-BSI by current guidelines. The potential of the lipid S ELISA to facilitate the diagnosis of CR-BSI in 38 haematology/SCT patients and sternal SSI in 57 cardiothoracic surgery patients was also assessed. The ELISA proved to be a sensitive test for the rapid serodiagnosis of infection due to staphylococci in immunocompetent patients. The acridine orange leucocyte cytospin test (AOLC) was also evaluated for the rapid diagnosis of CR-BSI in 16 haematology/SCT patients with Hickman CVC in situ. Although the sensitivity of the test was low, it may provide a useful adjunct to conventional methods for the in situ sampling of catheters to predict and diagnose CR-BSI, preventing the unnecessary removal of CVC.

Chlorhexidine and the prevention of surgical site infection

Surgical site infections (SSI) are a prevalent health care-associated infection (HAl). Prior to the mid-19th century, surgical sites commonly developed postoperative wound complications. It was in the 1860's, after Joseph Lister introduced carbolic acid and the principles of antisepsis that postoperative wound infection significantly decreased. Today, patient preoperative skin preparation with an antiseptic agent prior to surgery is a standard of practice. Povidone-iodine and chlorhexidine gluconate are currently the most commonly used antimicrobial agents used to prep the patient's skin. In this current study, the epidemiology, diagnosis, surveillance and prevention of SSI with chlorhexidine were investigated. The antimicrobial activity of chlorhexidine was assessed. In in-vitro and in-vivo studies the antimicrobial efficacy of 2% (w/v) chlorhexidine gluconate (CHG) in 70% isopropyl alcohol (IPA) and 10% povidoneiodine (PVP-I) in the presence of 0.9% normal saline or blood were examined. The 2% CHG in 70% IPA solutions antimicrobial activity was not diminished in the presence of 0.9% normal saline or blood. In comparison, the traditional patient preoperative skin preparation, 10% PVP-I antimicrobial activity was not diminished in the presence of 0.9% normal saline, but was diminished in the presence of blood. In an in-vivo human volunteer study the potential for reduction of the antimicrobial efficacy of aqueous patient preoperative skin preparations compromised by mechanical removal of wet product from the application site (blot) was assessed. In this evaluation, 2% CHG and 10% povidone-iodine (PVP-I) were blotted from the patient's skin after application to the test site. The blotting, or mechanical removal, of the wet antiseptic from the application site did not produce a significant difference in product efficacy. In a clinical trial to compare 2% CHG in 70% IPA and PVP-! scrub and paint patient preoperative skin preparation for the prevention of SSI, there were 849 patients randomly assigned to the study groups (409 in the chlorhexidine-alcohol and 440 in the povidone-iodine group) in the intention-to-treat analysis. The overall surgical site infection was significantly lower in the 2% CHG in 70% IPA group than in the PVP-I group (9.5% versus 16.1 %, p=0.004; relative risk, 0.59 with 95% confidence interval of 0.41 to 0.85). Preoperative cleansing of the patient's skin with chlorhexidine-alcohol is superior to povidone-iodine in preventing surgical site infection after clean-contaminated surgery.

Identification of aspirin analogues that repress NF-κB signalling and demonstrate anti-proliferative activity towards colorectal cancer in vitro and in vivo

Substantial evidence indicates that aspirin and related non-steroidal anti-inflammatory drugs (NSAIDs) have potential as chemopreventative/therapeutic agents. However, these agents cannot be universally recommended for prevention purposes due to their potential side-effect profiles. Here, we compared the growth inhibitory and mechanistic activity of aspirin to two novel analogues, diaspirin (DiA) and fumaryl diaspirin (F-DiA). We found that the aspirin analogues inhibited cell proliferation and induced apoptosis of colorectal cancer cells at significantly lower doses than aspirin. Similar to aspirin, we found that an early response to the analogues was a reduction in levels of cyclin D1 and stimulation of the NF-κB pathway. This stimulation was associated with a significant reduction in basal levels of NF-κB transcriptional activity, in keeping with previous data for aspirin. However, in contrast to aspirin, DiA and F-DiA activity was not associated with nucleolar accumulation of RelA. For all assays, F-DiA had a more rapid and significant effect than DiA, identifying this agent as particularly active against colorectal cancer. Using a syngeneic colorectal tumour model in mice, we found that, while both agents significantly inhibited tumour growth in vivo, this effect was particularly pronounced for F-DiA. These data identify two compounds that are active against colorectal cancer in vitro and in vivo. They also identify a potential mechanism of action of these agents and shed light on the chemical structures that may be important for the antitumour effects of aspirin.

Propionibacterium acnes:infection beyond the skin

Propionibacterium acnes is a Gram-positive bacterium that forms part of the normal flora of the skin, oral cavity, large intestine, the conjunctiva and the external ear canal. Although primarily recognized for its role in acne, P. acnes is an opportunistic pathogen, causing a range of postoperative and device-related infections. These include infections of the bones and joints, mouth, eye and brain. Device-related infections include those of joint prostheses, shunts and prosthetic heart valves. P. acnes may play a role in other conditions, including inflammation of the prostate leading to cancer, SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome, sarcoidosis and sciatica. If an active role in these conditions is established there are major implications for diagnosis, treatment and protection. Genome sequencing of the organism has provided an insight into the pathogenic potential and virulence of P. acnes. © 2011 Expert Reviews Ltd.

Use of structural equation modeling to examine the association between breast cancer risk perception and repeat screening mammography among United States women

Breast cancer is the second leading cause of cancer death in United States women, estimated to be diagnosed in 1 out of 8 women in their lifetime. Screening mammography detects breast cancer in its pre-clinical stages when treatment strategies have the greatest chance of success, and is currently the only population-wide prevention method proven to reduce the morbidity and mortality associated with breast cancer. Research has shown that the majority of women are not screened annually, with estimates ranging front 6% - 30% of eligible women receiving all available annual mammograms over a 5-year or greater time frame. Health behavior theorists believe that perception of risk/susceptibility to a disease influences preventive health behavior, in this case, screening mammography The purpose of this dissertation is to examine the association between breast cancer risk perception and repeat screening mammography using a structural equation modeling (SEM) framework. A series of SEM multivariate regressions were conducted using self-reported, nationally representative data from the 2005 National Health Interview Survey. Interaction contrasts were tested to measure the potential moderating effects of variables which have been shown to be predictive of mammography use (physician recommendation, economic barriers, structural barriers, race/ethnicity) on the association between breast cancer risk perception and repeat mammography, while controlling for the covariates of age, income, region, nativity, and educational level. Of the variables tested for moderation, results of the SEM analyses identify physician recommendation as the only moderator of the relationship between risk perception and repeat mammography, thus the potentially most effective point of intervention to increase mammography screening, and decrease the morbidity and mortality associated with breast cancer. These findings expand the role of the physician from recommendation to one of attenuating the effect of risk perception and increasing repeat screening. The long range application of the research is the use of the SEM methodology to identify specific points of intervention most likely to increase preventive behavior in population-wide research, allowing for the most effective use of intervention funds.^

Prevention of oral lesions in children with acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is the most common form of cancer in children and is responsible for severe stomatologic complications. Treatment consists of four phases of chemotherapy, the main side effect of methotrexate, the drug most used during the intensification phase, is oral mucositis. OBJECTIVE: To evaluate the clinical aspects of the oral mucosa of children with ALL and to determine the effect of 0.12% chlorhexidine gluconate on the prevention of stomatologic complications in these patients. PATIENTS AND METHODS: Thirty-three children treated for ALL ranging in age from 2 to 15 years, without distinction of gender or race, were submitted to visual examination, digital palpation of the oral mucosa and cytologic examination of the buccal mucosa, and divided into two groups: group I consisted of 23 children using an oral solution of 0.12% chlorhexidine gluconate twice a day, and group II consisted of 10 children who did not receive this solution. All children received daily oral hygiene care guided by the dentist throughout treatment. RESULTS: Mucositis was observed in six children of group I and eight of group II, and was characterized by erythema, edema and ulcers. Uniform cytologic findings were obtained for the two groups, with a clear predominance of cells of the intermediate layer in all smears, in addition to a perinuclear halo in 18% of the smears. CONCLUSION: The present results suggest that systematic preventive treatment with 0.12% chlorhexidine gluconate and oral hygiene care reduce the occurrence of oral complications in children with ALL undergoing antineoplastic chemotherapy.

Prevention of oral lesions in children with acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is the most common form of cancer in children and is responsible for severe stomatologic complications. Treatment consists of four phases of chemotherapy, the main side effect of methotrexate, the drug most used during the intensification phase, is oral mucositis. OBJECTIVE: To evaluate the clinical aspects of the oral mucosa of children with ALL and to determine the effect of 0.12% chlorhexidine gluconate on the prevention of stomatologic complications in these patients. PATIENTS AND METHODS: Thirty-three children treated for ALL ranging in age from 2 to 15 years, without distinction of gender or race, were submitted to visual examination, digital palpation of the oral mucosa and cytologic examination of the buccal mucosa, and divided into two groups: group I consisted of 23 children using an oral solution of 0.12% chlorhexidine gluconate twice a day, and group II consisted of 10 children who did not receive this solution. All children received daily oral hygiene care guided by the dentist throughout treatment. RESULTS: Mucositis was observed in six children of group I and eight of group II, and was characterized by erythema, edema and ulcers. Uniform cytologic findings were obtained for the two groups, with a clear predominance of cells of the intermediate layer in all smears, in addition to a perinuclear halo in 18% of the smears. CONCLUSION: The present results suggest that systematic preventive treatment with 0.12% chlorhexidine gluconate and oral hygiene care reduce the occurrence of oral complications in children with ALL undergoing antineoplastic chemotherapy.

Challenges, Strengths and Opportunities Related to Implementing Comprehensive Evidence-Based Guidelines on Breast Cancer Survivorship Care by Primary Care Physicians and Nurse Practitioners in Southeastern Ontario

Background Many breast cancer survivors continue to have a broad range of physical and psychosocial problems after breast cancer treatment. As cancer centres move forward with earlier discharge of stable breast cancer survivors to primary care follow-up it is important that comprehensive evidence-based breast cancer survivorship care is implemented to effectively address these needs. Research suggests primary care providers are willing to provide breast cancer survivorship care but many lack the knowledge and confidence to provide evidence-based care. Purpose The overall purpose of this thesis was to determine the challenges, strengths and opportunities related to implementing comprehensive evidence-based breast cancer survivorship guidelines by primary care physicians and nurse practitioners in southeastern Ontario. Methods This mixed-methods research was conducted in three phases: (1) synthesis and appraisal of clinical practice guidelines relevant to provision of breast cancer survivorship care within the primary care practice setting; (2) a brief quantitative survey of primary care providers to determine actual practices related to provision of evidence-based breast cancer survivorship care; and (3) individual interviews with primary care providers about the challenges, strengths and opportunities related to provision of comprehensive evidence-based breast cancer survivorship care. Results and Conclusions In the first phase, a comprehensive clinical practice framework was created to guide provision of breast cancer survivorship care and consisted of a one-page checklist outlining breast cancer survivorship issues relevant to primary care, a three-page summary of key recommendations, and a one-page list of guideline sources. The second phase identified several knowledge and practice gaps, and it was determined that guideline implementation rates were higher for recommendations related to prevention and surveillance aspects of survivorship care and lowest related to screening for and management of long-term effects. The third phase identified three major challenges to providing breast cancer survivorship care: inconsistent educational preparation, provider anxieties, and primary care burden; and three major strengths or opportunities to facilitate implementation of survivorship care guidelines: tools and technology, empowering survivors, and optimizing nursing roles. A better understanding of these challenges, strengths and opportunities will inform development of targeted knowledge translation interventions to provide support and education to primary care providers.

Multicenter randomized phase II clinical trial comparing neoadjuvant oxaliplatin, capecitabine, and preoperative radiotherapy with or without cetuximab followed by total mesorectal excision in patients with high-risk rectal cancer (EXPERT-C).

PURPOSE: To evaluate the addition of cetuximab to neoadjuvant chemotherapy before chemoradiotherapy in high-risk rectal cancer. PATIENTS AND METHODS: Patients with operable magnetic resonance imaging-defined high-risk rectal cancer received four cycles of capecitabine/oxaliplatin (CAPOX) followed by capecitabine chemoradiotherapy, surgery, and adjuvant CAPOX (four cycles) or the same regimen plus weekly cetuximab (CAPOX+C). The primary end point was complete response (CR; pathologic CR or, in patients not undergoing surgery, radiologic CR) in patients with KRAS/BRAF wild-type tumors. Secondary end points were radiologic response (RR), progression-free survival (PFS), overall survival (OS), and safety in the wild-type and overall populations and a molecular biomarker analysis. RESULTS: One hundred sixty-five eligible patients were randomly assigned. Ninety (60%) of 149 assessable tumors were KRAS or BRAF wild type (CAPOX, n = 44; CAPOX+C, n = 46), and in these patients, the addition of cetuximab did not improve the primary end point of CR (9% v 11%, respectively; P = 1.0; odds ratio, 1.22) or PFS (hazard ratio [HR], 0.65; P = .363). Cetuximab significantly improved RR (CAPOX v CAPOX+C: after chemotherapy, 51% v 71%, respectively; P = .038; after chemoradiation, 75% v 93%, respectively; P = .028) and OS (HR, 0.27; P = .034). Skin toxicity and diarrhea were more frequent in the CAPOX+C arm. CONCLUSION: Cetuximab led to a significant increase in RR and OS in patients with KRAS/BRAF wild-type rectal cancer, but the primary end point of improved CR was not met.

Peripheral Artery Disease Patients May Benefit More from Aggressive Secondary Prevention than Aneurysm Patients to Improve Survival

BACKGROUND AND AIMS: Although it has become clear that aneurysmal and occlusive arterial disease represent two distinct etiologic entities, it is still unknown whether the two vascular pathologies are prognostically different. We aim to assess the long-term vital prognosis of patients with abdominal aortic aneurysmal disease (AAA) or peripheral artery disease (PAD), focusing on possible differences in survival, prognostic risk profiles and causes of death. METHODS: Patients undergoing elective surgery for isolated AAA or PAD between 2003 and 2011 were retrospectively included. Differences in postoperative survival were determined using Kaplan-Meier and Cox regression analysis. Prognostic risk profiles were also established with Cox regression analysis. RESULTS: 429 and 338 patients were included in the AAA and PAD groups, respectively. AAA patients were older (71.7 vs. 63.3 years, p < 0.001), yet overall survival following surgery did not differ (HR: 1.16, 95% CI: 0.87-1.54). Neither was type of vascular disease associated with postoperative cardiovascular nor cancer-related death. However, in comparison with age- and gender-matched general populations, cardiovascular mortality was higher in PAD than AAA patients (48.3% vs. 17.3%). Survival of AAA and PAD patients was negatively affected by age, history of cancer and renal insufficiency. Additional determinants in the PAD group were diabetes and ischemic heart disease. CONCLUSIONS: Long-term survival after surgery for PAD and AAA is similar. However, overall life expectancy is significantly worse among PAD patients. The contribution of cardiovascular disease towards mortality in PAD patients warrants more aggressive secondary prevention to reduce cardiovascular mortality and improve longevity.