The burden of pancreatic cancer in Australia attributable to smoking.

OBJECTIVE: To estimate the burden of pancreatic cancer in Australia attributable to modifiable exposures, particularly smoking. DESIGN: Prospective pooled cohort study. SETTING, PARTICIPANTS: Seven prospective Australian study cohorts (total sample size, 365 084 adults); participant data linked to national registries to identify cases of pancreatic cancer and deaths. MAIN OUTCOME MEASURES: Associations between exposures and incidence of pancreatic cancer, estimated in a proportional hazards model, adjusted for age, sex, study, and other exposures; future burden of pancreatic cancer avoidable by changes in exposure estimated as population attributable fractions (PAFs) for whole population and for specific population subgroups with a method accounting for competing risk of death. RESULTS: There were 604 incident cases of pancreatic cancer during the first 10 years of follow-up. Current and recent smoking explained 21.7% (95% CI, 13.8-28.9%) and current smoking alone explained 15.3% (95% CI, 8.6-22.6%) of future pancreatic cancer burden. This proportion of the burden would be avoidable over 25 years were current smokers to quit and there were no new smokers. The burden attributable to current smoking is greater for men (23.9%; 95% CI, 13.3-33.3%) than for women (7.2%; 95% CI, -0.4% to 14.2%; P = 0.007) and for those under 65 (19.0%; 95% CI, 8.1-28.6%) than for older people (6.6%; 95% CI, 1.9-11.1%; P = 0.030). There were no independent relationships between body mass index or alcohol consumption and pancreatic cancer. CONCLUSIONS: Strategies that reduce the uptake of smoking and encourage current smokers to quit could substantially reduce the future incidence of pancreatic cancer in Australia, particularly among men.

Borderline grades in high stakes clinical examinations: resolving examiner uncertainty.

BACKGROUND: Objective Structured Clinical Exams are used to increase reliability and validity, yet they only achieve a modest level of reliability. This low reliability is due in part to examiner variance which is greater than the variance of students. This variance often represents indecisiveness at the cut score with apparent confusion over terms such as "borderline pass". It is amplified by a well reported failure to fail. METHODS: A borderline grade (meaning performance is neither a clear pass nor a clear fail) was introduced in a high stakes undergraduate medical clinical skills exam to replace a borderline pass grade (which was historically resolved as 50%) in a 4 point scale (distinction, pass, borderline, fail). Each Borderline grade was then resolved into a Pass or Fail grade by a formula referencing the difficulty of the station and the performance in the same domain by the student in other stations. Raw pass or fail grades were unaltered. Mean scores and 95%CI were calculated per station and per domain for the unmodified and the modified scores/grades (results are presented on error bars). To estimate the defensibility of these modifications, similar analysis took place for the P and the F grades which resulted from the modification of the B grades. RESULTS: Of 14,634 observations 4.69% were Borderline. Application of the formula did not impact the mean scores in each domain but the failure rate for the exam increased from 0.7 to 4.1%. Examiners and students expressed satisfaction with the Borderline grade, resolution formula and outcomes. Mean scores (by stations and by domains respectively) of students whose B grades were modified to P were significantly higher than their counterparts whose B grades were modified to F. CONCLUSIONS: This study provides a feasible and defensible resolution to situations where the examinee's performance is neither a clear pass nor a clear fail, demonstrating the application of the resolution of borderline formula in a high stakes exam. It does not create a new performance standard but utilises real data to make judgements about these small number of candidates. This is perceived as a fair approach to Pass/Fail decisions.

Rising incidence of early-onset colorectal cancer in Australia over two decades: report and review.

The average age at diagnosis for colorectal cancer (CRC) in Australia is 69, and the age-specific incidence rises rapidly after age 50 years. The incidence has stabilized or is declining in older age groups in Australia during recent decades, possibly related to the increased uptake of screening and high-risk surveillance. In the same time frame, a rising incidence of CRC in younger adults has been well-documented in the United States. This rise in incidence in the young has not been reported from other countries that share long-term exposure to westernised urban lifestyles. Using data from the Australian Institute of Health and Welfare, we examined trends in national incidence rates for CRC under age 50 years and observed that rates in people under age 40 years have been rising for the last two decades. We further performed a review of the literature regarding CRC in young adults to outline the extent of current understanding, explore potential risk factors such as obesity, alcohol, and sedentary lifestyles, and to identify the questions remaining to be addressed. Although absolute numbers might not justify a population screening approach, the dispersal of young adults with CRC across the primary health-care system decreases probability of their recognition. Patient and physician awareness, aided by stool and emerging blood-screening tests and risk profiling tools, have the potential to aid in identification of those young adults who would most benefit from a colonoscopy through early detection of CRCs or by removal of advanced polyps.

Patients who take their symptoms less seriously are more likely to have colorectal cancer.

BACKGROUND: People vary in how they respond to symptoms. The purpose of this study was to assess whether serious disease is more likely to be present in patients who report that they take any symptoms less seriously than other people do, and to assess the reliability of a question which can be used to identify the extent to which patients take any symptom seriously. To do this we assessed whether the likelihood of detecting colorectal cancer is higher in patients who report that they take symptoms less seriously than other people do. METHODS: Cross sectional study of 7736 patients who had colonoscopy to find colorectal cancer. Before colonoscopy, patients completed a questionnaire on bowel symptoms and were also asked: "Compared to other people of your age and sex, how seriously do you think you take any symptoms?" Likelihood of detecting colorectal cancer according to responses to this question was assessed by logistic regression models, unadjusted and adjusted for symptoms and other known predictors of colorectal cancer.Question reliability was assessed in a different sample using percentage agreement and the kappa statistic for the answers given by each patient on two occasions. Agreement between patient and doctor responses was also assessed (n = 108). RESULTS: Patients who reported they took symptoms less seriously were 3.28 (95%CI: 2.02, 5.33) times more likely to have colorectal cancer than patients who took symptoms more seriously than others. The effect was smaller (1.85 (95%CI: 1.11, 3.09)), but remained statistically significant in models including symptoms and other predictors of colorectal cancer. The question was reliable: on repeat questioning, 70% of responses were in absolute agreement and 92% were within 1 category, kappa 57%. Patient-doctor agreement was 66%, within 1 category 92%, kappa 48%. CONCLUSION: Patients who take their symptoms less seriously have a considerably higher likelihood of colorectal cancer than those who identify themselves as taking any symptoms more seriously than other people. The question is easy to ask and has good reliability. Doctors also reliably identify how patients assess themselves. Assessment of how seriously patients take any symptoms can contribute to the clinical assessment of a patient.

Most bowel cancer symptoms do not indicate colorectal cancer and polyps: a systematic review.

BACKGROUND: Bowel symptoms are often considered an indication to perform colonoscopy to identify or rule out colorectal cancer or precancerous polyps. Investigation of bowel symptoms for this purpose is recommended by numerous clinical guidelines. However, the evidence for this practice is unclear. The objective of this study is to systematically review the evidence about the association between bowel symptoms and colorectal cancer or polyps. METHODS: We searched the literature extensively up to December 2008, using MEDLINE and EMBASE and following references. For inclusion in the review, papers from cross sectional, case control and cohort studies had to provide a 2×2 table of symptoms by diagnosis (colorectal cancer or polyps) or sufficient data from which that table could be constructed. The search procedure, quality appraisal, and data extraction was done twice, with disagreements resolved with another reviewer. Summary ROC analysis was used to assess the diagnostic performance of symptoms to detect colorectal cancer and polyps. RESULTS: Colorectal cancer was associated with rectal bleeding (AUC 0.66; LR+ 1.9; LR- 0.7) and weight loss (AUC 0.67, LR+ 2.5, LR- 0.9). Neither of these symptoms was associated with the presence of polyps. There was no significant association of colorectal cancer or polyps with change in bowel habit, constipation, diarrhoea or abdominal pain. Neither the clinical setting (primary or specialist care) nor study type was associated with accuracy.Most studies had methodological flaws. There was no consistency in the way symptoms were elicited or interpreted in the studies. CONCLUSIONS: Current evidence suggests that the common practice of performing colonoscopies to identify cancers in people with bowel symptoms is warranted only for rectal bleeding and the general symptom of weight loss. Bodies preparing guidelines for clinicians and consumers to improve early detection of colorectal cancer need to take into account the limited value of symptoms.

The value of age and medical history for predicting colorectal cancer and adenomas in people referred for colonoscopy.

BACKGROUND: Colonoscopy is an invasive and costly procedure with a risk of serious complications. It would therefore be useful to prioritise colonoscopies by identifying people at higher risk of either cancer or premalignant adenomas. The aim of this study is to assess a model that identifies people with colorectal cancer, advanced, large and small adenomas. METHODS: Patients seen by gastroenterologists and colorectal surgeons between April 2004 and December 2006 completed a validated, structured self-administered questionnaire prior to colonoscopy. Information was collected on symptoms, demographics and medical history. Multinomial logistic regression was used to simultaneously assess factors associated with findings on colonoscopy of cancer, advanced adenomas and adenomas sized 6 -9 mm, and ≤ 5 mm. The area under the curve of ROC curve was used to assess the incremental gain of adding demographic variables, medical history and symptoms (in that order) to a base model that included only age. RESULTS: Sociodemographic variables, medical history and symptoms (from 8,204 patients) jointly provide good discrimination between colorectal cancer and no abnormality (AUC 0.83), but discriminate less well between adenomas and no abnormality (AUC advanced adenoma 0.70; other adenomas 0.67). Age is the dominant risk factor for cancer and adenomas of all sizes. Having a colonoscopy within the last 10 years confers protection for cancers and advanced adenomas. CONCLUSIONS: Our models provide guidance about which factors can assist in identifying people at higher risk of disease using easily elicited information. This would allow colonoscopy to be prioritised for those for whom it would be of most benefit.

Definition of professionalism and tools for assessing professionalism in pharmacy practice: a systemic review.

PURPOSE: In contemporary pharmacy, the role of pharmacists has become more multifaceted as they now handle a wider range of tasks and take more responsibility for care provision for patients than 20 years ago. Such an evolution in the pharmacist's responsibilities is accompanied by the need for pharmacists to display high-quality patient-centred care and counselling, and to demonstrate professionalism, which now needs to be taught and assessed are part of pharmacy education and practice. This workaimed at identifying definition of professionalism in pharmacy practice and critically evaluatingpublished instruments for assessing professionalism in pharmacy practice. METHODS: We searched the medical literature listed in Scopus, Medline, andPsycINFOdatabasesfrom 1 January 2000 to 31 December 2018. All papers meeting our selection criteria, were reviewed and summarised into a clear review of professionalism requirements in pharmacy practice. Details of the instruments measuring professionalism were reviewed in detail. RESULTS: There is no accepted simple definition of professionalism, although we identified several theoretical and policy frameworks required for professional pharmaceutical practice. We identified 4 instruments (Behavioural Professionalism Assessment Instrument (BPAI), Lerkiatbundit's Instrument, Pharmacy Professionalism Instrument (PPI) and Professionalism Assessment Tool (PAT) that build on these frameworks and measure professional practice in pharmacy students. These were found to be reliable and valid but had only been used and tested in student populations. CONCLUSION: Given the increasing role of community pharmacisits there is a need for assessment of professionalism in practice. Professionalism is a complex concept that is challenging to measure because it has no standardised definition and existing literature related to the topic is limited. Current instruments available focus on measuring the development of the elements of professionalism among pharmacy students rather than pharmacists.

A self administered reliable questionnaire to assess lower bowel symptoms.

BACKGROUND: Bowel symptoms are considered indicators of the presence of colorectal cancer and other bowel diseases. Self administered questionnaires that elicit information about lower bowel symptoms have not been assessed for reliability, although this has been done for upper bowel symptoms. Our aim was to develop a self administered questionnaire for eliciting the presence, nature and severity of lower bowel symptoms potentially related to colorectal cancer, and assess its reliability. METHODS: Immediately before consulting a gastroenterologist or colorectal surgeon, 263 patients likely to have a colonoscopy completed the questionnaire. Reliability was assessed in two ways: by assessing agreement between patient responses and (a) responses given by the doctor at the consultation; and (b) responses given by patients two weeks later. RESULTS: There was more than 75% agreement for 78% of the questions for the patient-doctor comparison and for 92% of the questions for the patient-patient comparison. Agreement for the length of time a symptom was present, its severity, duration, frequency of occurrence and whether or not medical consultation had been sought, all had agreement of greater than 70%. Over all questions, the chance corrected agreement for the patient-doctor comparison had a median kappa of 65% (which represents substantial agreement), interquartile range 57-72%. The patient-patient comparison also showed substantial agreement with a median kappa of 75%, interquartile range 68-81%. CONCLUSION: This self administered questionnaire about lower bowel symptoms is a useful way of eliciting details of bowel symptoms. It is a reliable instrument that is acceptable to patients and easily completed. Its use could guide the clinical consultation, allowing a more efficient, comprehensive and useful interaction, ensuring that all symptoms are assessed. It will also be a useful tool in research studies on bowel symptoms and their predictive value for colorectal cancer and other diseases. Studies assessing whether bowel symptoms predict the presence of colorectal cancer should provide estimates of the reliability of the symptom elicitation.

Examiner seniority and experience are associated with bias when scoring communication, but not examination, skills in objective structured clinical examinations in Australia.

PURPOSE: The biases that may influence objective structured clinical examination (OSCE) scoring are well understood, and recent research has attempted to establish the magnitude of their impact. However, the influence of examiner experience, clinical seniority, and occupation on communication and physical examination scores in OSCEs has not yet been clearly established. METHODS: We compared the mean scores awarded for generic and clinical communication and physical examination skills in 2 undergraduate medicine OSCEs in relation to examiner characteristics (gender, examining experience, occupation, seniority, and speciality). The statistical significance of the differences was calculated using the 2-tailed independent t-test and analysis of variance. RESULTS: Five hundred and seventeen students were examined by 237 examiners at the University of New South Wales in 2014 and 2016. Examiner gender, occupation (academic, clinician, or clinical tutor), and job type (specialist or generalist) did not significantly impact scores. Junior doctors gave consistently higher scores than senior doctors in all domains, and this difference was statistically significant for generic and clinical communication scores. Examiner experience was significantly inversely correlated with generic communication scores. CONCLUSION: We suggest that the assessment of examination skills may be less susceptible to bias because this process is fairly prescriptive, affording greater scoring objectivity. We recommend training to define the marking criteria, teaching curriculum, and expected level of performance in communication skills to reduce bias in OSCE assessment.

The Future Colorectal Cancer Burden Attributable to Modifiable Behaviors: A Pooled Cohort Study.

BACKGROUND: Previous estimates of the colorectal cancer (CRC) burden attributed to behaviors have not considered joint effects, competing risk, or population subgroup differences. METHODS: We pooled data from seven prospective Australian cohort studies (n = 367 058) and linked them to national registries to identify CRCs and deaths. We estimated the strength of the associations between behaviors and CRC risk using a parametric piecewise constant hazards model, adjusting for age, sex, study, and other behaviors. Exposure prevalence was estimated from contemporary National Health Surveys. We calculated population attributable fractions for CRC preventable by changes to current behaviors, accounting for competing risk of death and risk factor interdependence. Statistical tests were two-sided. RESULTS: During the first 10 years of follow-up, there were 3471 incident CRCs. Overweight or obesity explained 11.1%, ever smoking explained 10.7% (current smoking 3.9%), and drinking more than two compared with two or fewer alcoholic drinks per day explained 5.8% of the CRC burden. Jointly, these factors were responsible for 24.9% (95% confidence interval [CI] = 19.7% to 29.9%) of the burden, higher for men (36.7%) than women (13.2%, P difference < .001). The burden attributed to these factors was also higher for those born in Australia (28.7%) than elsewhere (16.8%, P difference = .047). We observed modification of the smoking-attributable burden by alcohol consumption and educational attainment, and modification of the obesity-attributable burden by age group and birthplace. CONCLUSIONS: We produced up-to-date estimates of the future CRC burden attributed to modifiable behaviors. We revealed novel differences between men and women, and other high-CRC burden subgroups that could potentially benefit most from programs that support behavioral change and early detection.

The future burden of lung cancer attributable to current modifiable behaviours: a pooled study of seven Australian cohorts.

Background: Knowledge of preventable disease and differences in disease burden can inform public health action to improve health and health equity. We quantified the future lung cancer burden preventable by behavioural modifications across Australia. Methods: We pooled seven Australian cohort studies (n = 367 058) and linked them to national registries to identify lung cancers and deaths. We estimated population attributable fractions and their 95% confidence intervals (CIs) for modifiable risk factors, using risk estimates from the cohort data and risk factor exposure distribution from contemporary national health surveys. Results: During the first 10-year follow-up, there were 2025 incident lung cancers and 20 349 deaths. Stopping current smoking could prevent 53.7% (95% CI, 50.0-57.2%) of lung cancers over 40 years and 18.3% (11.0-25.1%) in 10 years. The smoking-attributable burden is highest in males, those who smoke <20 cigarettes per day, are <75 years of age, unmarried, of lower educational attainment, live in remote areas or are healthy weight. Increasing physical activity and fruit consumption, if causal, could prevent 15.6% (6.9-23.4%) and 7.5% (1.3-13.3%) of the lung cancer burden, respectively. Jointly, the three behaviour modifications could prevent up to 63.0% (58.0-67.5%) of lung cancers in 40 years, and 31.2% (20.9-40.1%) or 43 300 cancers in 10 years. The preventable burden is highest among those with multiple risk factors. Conclusions: Smoking remains responsible for the highest burden of lung cancer in Australia. The uneven burden distribution distinguishes subgroups that could benefit the most from activities to control the world's deadliest cancer.

Availability and development of guidelines in a tertiary teaching hospital.

OBJECTIVE: The purpose of this study was to review existing guidelines in clinical departments and describe their characteristics, development and implementation at a large teaching hospital in Sydney, Australia. METHODS: The study was undertaken in two stages. First, from September to November 2005, we reviewed and classified documents from eight departments as clinical practice guidelines (CPGs), clinical procedural protocols (technology and technique) or administrative guidelines. We also collected information about the scope, format and target user of the guidelines. Second, from March to June 2006, we interviewed department staff in seven of eight participating departments about the guidelines' development and implementation. A revised Appraisal of Guidelines Research and Evaluation questionnaire was used to collect data in both stages. RESULTS: A total of 368 of 509 documents reviewed were classified as CPGs. Almost 90% of the CPGs had five or fewer pages; nearly 80% had no references; and 90% had no application tools. The CPGs had been developed locally by each individual department. The departments used various methods to collect evidence. In six (albeit a different six departments in each case) of seven departments, clinicians' clinical experience was used in the analysis of the evidence; informal expert consensus was used for formulating recommendations; internal peer review was the major method used to review the guidelines (after drafting); hard copy of guidelines was the major medium used; and provision of educational material was the major implementation strategy. CONCLUSIONS: There was great variation in the number, availability and presentation of guidelines in the departments. There was a lack of standardized methods and narrow skills representation during guideline development.

The sights and insights of examiners in objective structured clinical examinations.

PURPOSE: The objective structured clinical examination (OSCE) is considered to be one of the most robust methods of clinical assessment. One of its strengths lies in its ability to minimise the effects of examiner bias due to the standardisation of items and tasks for each candidate. However, OSCE examiners' assessment scores are influenced by several factors that may jeopardise the assumed objectivity of OSCEs. To better understand this phenomenon, the current review aims to determine and describe important sources of examiner bias and the factors affecting examiners' assessments. METHODS: We performed a narrative review of the medical literature using Medline. All articles meeting the selection criteria were reviewed, with salient points extracted and synthesised into a clear and comprehensive summary of the knowledge in this area. RESULTS: OSCE examiners' assessment scores are influenced by factors belonging to 4 different domains: examination context, examinee characteristics, examinee-examiner interactions, and examiner characteristics. These domains are composed of several factors including halo, hawk/dove and OSCE contrast effects; the examiner's gender and ethnicity; training; lifetime experience in assessing; leadership and familiarity with students; station type; and site effects. CONCLUSION: Several factors may influence the presumed objectivity of examiners' assessments, and these factors need to be addressed to ensure the objectivity of OSCEs. We offer insights into directions for future research to better understand and address the phenomenon of examiner bias.

Validating a proxy for disease progression in metastatic cancer patients using prescribing and dispensing data.

BACKGROUND: Routine data collections are used increasingly to examine outcomes of real-world cancer drug use. These datasets lack clinical details about important endpoints such as disease progression. AIM: To validate a proxy for disease progression in metastatic cancer patients using prescribing and dispensing claims. METHODS: We used data from a cohort study of patients undergoing chemotherapy who provided informed consent to the collection of cancer-treatment data from medical records and linkage to pharmaceutical claims. We derived proxy decision rules based on changes to drug treatment in prescription histories (n = 36 patients) and validated the proxy in prescribing data (n = 62 patients). We adapted the decision rules and validated the proxy in dispensing data (n = 109). Our gold standard was disease progression ascertained in patient medical records. Individual progression episodes were the unit of analysis for sensitivity and Positive Predictive Value (PPV) calculations and specificity and Negative Predictive Value (NPV) were calculated at the patient level. RESULTS: The sensitivity of our proxy in prescribing data was 74.3% (95% Confidence Interval (CI), 55.6-86.6%) and PPV 61.2% (95% CI, 45.0-75.3%); specificity and NPV were 87.8% (95% CI, 73.8-95.9%) and 100% (95% CI, 90.3-100%), respectively. In dispensing data, the sensitivity of our proxy was 64% (95% CI, 55.0-77.0%) and PPV 56.0% (95% CI, 43.0-69.0%); specificity and NPV were 81% (95% CI, 70.05-89.0%) and 91.0% (95% CI, 82.0-97.0%), respectively. CONCLUSION: Our proxy overestimated episodes of disease progression. The proxy's performance is likely to improve if the date of prescribing is used instead of date of dispensing in claims data and by incorporating medical service claims (such as imaging prior to drug changes) in the algorithm. Our proxy is not sufficiently robust for use in real world comparative effectiveness research for cancer medicines.

The burden of cancer attributable to modifiable risk factors: the Australian cancer-PAF cohort consortium.

PURPOSE: To estimate the Australian cancer burden attributable to lifestyle-related risk factors and their combinations using a novel population attributable fraction (PAF) method that accounts for competing risk of death, risk factor interdependence and statistical uncertainty. PARTICIPANTS: 365 173 adults from seven Australian cohort studies. We linked pooled harmonised individual participant cohort data with population-based cancer and death registries to estimate exposure-cancer and exposure-death associations. Current Australian exposure prevalence was estimated from representative external sources. To illustrate the utility of the new PAF method, we calculated fractions of cancers causally related to body fatness or both tobacco and alcohol consumption avoidable in the next 10 years by risk factor modifications, comparing them with fractions produced by traditional PAF methods. FINDINGS TO DATE: Over 10 years of follow-up, we observed 27 483 incident cancers and 22 078 deaths. Of cancers related to body fatness (n=9258), 13% (95% CI 11% to 16%) could be avoided if those currently overweight or obese had body mass index of 18.5-24.9 kg/m2. Of cancers causally related to both tobacco and alcohol (n=4283), current or former smoking explains 13% (11% to 16%) and consuming more than two alcoholic drinks per day explains 6% (5% to 8%). The two factors combined explain 16% (13% to 19%): 26% (21% to 30%) in men and 8% (4% to 11%) in women. Corresponding estimates using the traditional PAF method were 20%, 31% and 10%. Our PAF estimates translate to 74 000 avoidable body fatness-related cancers and 40 000 avoidable tobacco- and alcohol-related cancers in Australia over the next 10 years (2017-2026). Traditional PAF methods not accounting for competing risk of death and interdependence of risk factors may overestimate PAFs and avoidable cancers. FUTURE PLANS: We will rank the most important causal factors and their combinations for a spectrum of cancers and inform cancer control activities.

High participation rates are not necessary for cost-effective colorectal cancer screening.

BACKGROUND: In many countries high participation is an explicit target in screening programmes. The desire for high participation often appears to drive screening policy, although it is increasingly recognized that encouraging high participation may impinge upon the rights of an individual to make an informed choice. One argument offered in support of high participation is that it improves the cost-effectiveness of screening. This is questionable on theoretical grounds, and empirically there are conflicting results. Two recent cost-effectiveness models of faecal occult blood test (FOBT) screening for colorectal cancer (CRC) showed that cost-effectiveness was improved, another showed that cost-effectiveness was worsened and a fourth indicated that cost-effectiveness was unaffected by increasing the participation rate. METHODS: We assessed the extent to which different levels and patterns of participation affect cost-effectiveness, using decision modelling of three CRC screening with FOBT scenarios. We estimate the incremental cost-effectiveness (value for money) ratios for each scenario. RESULTS: The way in which participation is modelled, particularly assumptions made about the subsequent screening behaviour of non-participants ("if" and "when" a non-participant attends for subsequent screening), affects the cost-effectiveness estimates for FOBT screening programmes. 100% participation in all screening rounds gives a cost per life year saved (LYS) of USD 9705. Cost-effectiveness is worst when people who do not take part in one screening round (initial or subsequent) never take part in any future rounds of screening. Under this scenario, a participation rate of 20% in second and subsequent rounds gives a cost per LYS of USD 29,500. Under more realistic assumptions, for example the attendance of even a small proportion of non-participants in subsequent rounds, cost-effectiveness is more favourable and similar to that achieved for full participation: the scenario with a random participation rate of 20% in second and subsequent rounds for both participants and non-participants has a cost per LYS of USD 11,270. CONCLUSIONS: Contrary to a commonly held view, high participation in screening programmes is not necessary to achieve cost-effectiveness. Setting high target participation rates in screening programmes does not guarantee cost-effectiveness and may in certain circumstances reduce the cost-effectiveness.

Rapid response systems: a prospective study of response times.

PURPOSE: The purpose of the study was to evaluate the time taken for delivery of each component of care following patient deterioration and to assess the effect on response times of strategies implemented to improve the system. METHODS: A model identifying the sequence of organizational responses following a patient's unexpected clinical deterioration was developed. The time to key events and interventions from initial deterioration was measured for 3 months in 2005 and again in 2006 at a tertiary care hospital with a rapid response team (RRT) in place. Strategies to improve compliance with the RRT system were introduced between the 2 periods. RESULTS: The number of acute deterioration episodes identified increased (61 episodes in 2005; 154 episodes in 2006), but there was no improvement in response times. The 2 components contributing most frequently to delays were the time for nursing staff to call for assistance and, where needed, for physicians to call for higher-level care. Overall, 26% of episodes in 2006 and 30% in 2005 did not receive medical attention within 30 minutes of acute deterioration. CONCLUSIONS: Significant delays in responding to acute deterioration persist despite strategies to facilitate the functioning of the RRT system. Simple strategies such as policy directives are not sufficient to effect change in complex health care systems.

A systematic review and meta-analysis of KRAS status as the determinant of response to anti-EGFR antibodies and the impact of partner chemotherapy in metastatic colorectal cancer.

BACKGROUND: In the setting of metastatic colorectal cancer (CRC), anti-EGFR antibodies are not currently recommended for individuals with KRAS mutant tumours. This is based on subgroup analyses of individual clinical trials rather than a formal synthesis of evidence for KRAS status as a predictive biomarker, while newer trials report no benefit for anti-EGFR antibodies irrespective of KRAS status. This study systematically reviewed the evidence for KRAS mutation status as a treatment effect modifier of response to anti-EGFR antibodies and the influence of partner chemotherapy. METHODS: Medline (1966-2010), EMBASE and American and European oncology meeting abstracts were searched for randomised controlled trials reporting the influence of KRAS status on effectiveness of anti-EGFR antibodies in metastatic CRC. The treatment efficacy was summarised by KRAS status using hazard ratios (HR) for progression-free survival (PFS) and risk differences (RD) for objective response. For each study, a measure of effect modification was calculated, and aggregated using random effects meta-analysis to assess the interaction between KRAS and treatment effect. FINDINGS: Eleven studies (8924 patients) were selected from 198 reports. Two studies assessed anti-EGFR antibodies as monotherapy and nine their use with chemotherapy. KRAS status was reported in 7555 cases. In subgroup analysis, the progression HR for KRAS wild patients assigned to anti-EGFR antibodies was 0.80 (4436 patients 95%CI: 0.64, 0.99) and for mutant cases 1.11 (3119 patients, 95%CI: 0.97, 1.27). A significant treatment effect interaction between KRAS status and addition of anti-EGFR antibodies to standard treatment was found for PFS (ratio of HRs 0.71, 95%CI: 0.57, 0.90 p=0.005) and response rate difference (difference in RDs 15%, 95%CI: 8, 22%, p<0.001). There was no evidence that the extent of effect modification differed between chemotherapeutic partners for both PFS (p=0.3) and response rate (p=0.6). INTERPRETATION: KRAS mutation status is a treatment effect modifier for anti-EGFR antibodies in metastatic CRC. Further evidence is needed to determine whether this is true for all chemotherapy partners and all clinical circumstances.