Benefits and Challenges of Treat-to-Target in Inflammatory Bowel Disease.

There is notable disparity between symptomatology and disease activity in a significant proportion of patients with inflammatory bowel disease (IBD), and escalation of treatment based on symptoms alone can fail to significantly alter the course of disease. The STRIDE-II position statement, published in 2021 by the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative of the International Organisation for the Study of IBD (IOIBD) provides the most current recommendations for a treat-to-target (T2T) approach in IBD. Despite the benefits offered by a T2T approach in IBD, there are numerous drawbacks and current limitations to its widespread implementation in real-world clinical practice. Owing to the lack of a standardised definition of MH, outcome data are heterogeneous and limit the comparability of existing data. Further, studies investigating the likelihood of achieving MH with a T2T approach are limited and largely retrospective. Evidence of the real-world feasibility of tight monitoring is currently minimal and demonstrates sub-optimal adherence among patients. Further, the few studies on the acceptability and uptake of a T2T approach in real-world practice demonstrate the need for increased acceptability on both patients' and clinicians' behalf. Real-world applicability is further limited by the need for repeated endoscopic assessments of MH as well as a lack of guidance on how to incorporate the various treatment targets into therapeutic decision-making. We aim to review the benefits and challenges of the T2T approach and to discuss potential solutions to further patient care.

A scoping review and meta-analysis on the prevalence of pan-tumour biomarkers (dMMR, MSI, high TMB) in different solid tumours.

Immune checkpoint inhibitors have been approved in the USA for tumours exhibiting mismatch repair deficiency (dMMR), microsatellite instability (MSI), or high tumour mutational burden (TMB), with regulatory and reimbursement applications in multiple other countries underway. As the estimated budget impacts of future reimbursements depend on the size of the potential target population, we performed a scoping review and meta-analysis of the prevalence of these pan-tumour biomarkers in different cancers. We systematically searched Medline/Embase and included studies reporting the prevalence of dMMR/MSI/high TMB in solid tumours published 01/01/2018-31/01/2021. Meta-analyses were performed separately for the pan-cancer prevalence of each biomarker, and by cancer type and stage where possible. The searches identified 3890 papers, with 433 prevalence estimates for 32 different cancer types from 201 studies included in meta-analyses. The pooled overall prevalence of dMMR, MSI and high TMB (≥ 10 mutations/Mb) in pan-cancer studies was 2.9%, 2.7% and 14.0%, respectively. The prevalence profiles of dMMR/MSI and high TMB differed across cancer types. For example, endometrial, colorectal, small bowel and gastric cancers showed high prevalence of both dMMR and MSI (range: 8.7-26.8% and 8.5-21.9%, respectively) and high TMB (range: 8.5-43.0%), while cervical, esophageal, bladder/urothelial, lung and skin cancers showed low prevalence of dMMR and MSI (< 5%), but high prevalence of high TMB (range: 23.7-52.6%). For other cancer types, prevalence of all three biomarkers was generally low (< 5%). This structured review of dMMR/MSI/high TMB prevalence across cancers and for specific cancer types and stages provide timely evidence to inform budget impact forecasts in health technology assessments for drug approvals based on these pan-tumour biomarkers.

The predicted effect and cost-effectiveness of tailoring colonoscopic surveillance according to mismatch repair gene in patients with Lynch syndrome.

PURPOSE: Lynch syndrome-related colorectal cancer (CRC) risk substantially varies by mismatch repair (MMR) gene. We evaluated the health impact and cost-effectiveness of MMR gene-tailored colonoscopic surveillance. METHODS: We first estimated sex- and MMR gene-specific cumulative lifetime risk of first CRC without colonoscopic surveillance using an optimization algorithm. Next, we harnessed these risk estimates in a microsimulation model, "Policy1-Lynch," and compared 126 colonoscopic surveillance strategies against no surveillance. RESULTS: The most cost-effective strategy was 3-yearly surveillance from age 25 to 70 years (pathogenic variants [path_] in MLH1 [path_MLH1], path_MSH2) with delayed surveillance for path_MSH6 (age 30-70 years) and path_PMS2 (age 35-70 years) heterozygotes (incremental cost-effectiveness ratio = Australian dollars (A) $8,833/life-year saved). This strategy averted 60 CRC deaths (153 colonoscopies per death averted) over the lifetime of 1000 confirmed patients with Lynch syndrome (vs no surveillance). This also reduced colonoscopies by 5% without substantial change in health outcomes (vs nontailored 3-yearly surveillance from 25-70 years). Generally, starting surveillance at age 25 (vs 20) years was more cost-effective with minimal effect on life-years saved and starting 5 to 10 years later for path_MSH6 and path_PMS2 heterozygotes (vs path_MLH1 and path_MSH2) further improved cost-effectiveness. Surveillance end age (70/75/80 years) had a minor effect. Three-yearly surveillance strategies were more cost-effective (vs 1 or 2-yearly) but prevented 3 fewer CRC deaths. CONCLUSION: MMR gene-specific colonoscopic surveillance would be effective and cost-effective.

Colon Capsule Endoscopy in the Assessment of Mucosal Healing in Crohn's Disease.

BACKGROUND: Patients with Crohn's disease (CD) undergo frequent endoscopic procedures, with visualization of the gastrointestinal mucosa central to treatment decision-making. Subsequently, a noninvasive alternative to optical colonoscopy (OC) would be welcomed. One such technology is capsule endoscopy, including the PillCam COLON 2 (PCC2), though research validating its use in ileocolonic CD is limited. This study aims to compare PCC2 with ileocolonoscopy (OC) in assessing mucosal CD through use of a standardized scoring system. METHODS: At an Australian tertiary hospital, same-day PCC2 and ileocolonoscopy results of 47 CD patients, with known nonstricturing disease, were prospectively collected and analyzed for correlation and agreement. Deidentified recordings were reported by a single expert gastroenterologist. Mucosal disease was quantified using the Simple Endoscopic Score for Crohn's Disease (SES-CD). The SES-CD results of paired endoscopic modalities were compared in total per bowel segment and per SES-CD variable. RESULTS: Of 47 PCC2 recordings, 68% were complete, fully assessing terminal ileum to rectum, and OC was complete in 89%. Correlation (r) between total SES-CD scores was strongest in the terminal ileum (r = 0.77, P < .001), with the SES-CD variable of "ulcer detection" showing the strongest agreement. The PCC2 (vs OC) identified additional ulcers in the terminal ileum; ascending, transverse, and descending colon; and rectum; scores were 5 (1), 5 (3), 1 (1), 2 (1), and 2 (2), respectively. CONCLUSIONS: The PCC2 shows promise in assessing ileocolonic mucosa, especially in proximal bowel segments, with greater reach of visualization in the small bowel. Given the resource and safety considerations raised by the Coronavirus disease 2019 pandemic, capsule endoscopy has particular significance.This article aims to contribute to the limited body of research surrounding the validity of capsule endoscopy technology in assessing ileocolonic mucosa in Crohn's Disease patients. In doing so, an alternative option for patients enduring frequent endoscopies is given potential.

Personal Protective Equipment for Endoscopy in Low-Resource Settings During the COVID-19 Pandemic: Guidance From the World Gastroenterology Organisation.

Performance of endoscopic procedures is associated with a risk of infection from COVID-19. This risk can be reduced by the use of personal protective equipment (PPE). However, shortage of PPE has emerged as an important issue in managing the pandemic in both traditionally high and low-resource areas. A group of clinicians and researchers from thirteen countries representing low, middle, and high-income areas has developed recommendations for optimal utilization of PPE before, during, and after gastrointestinal endoscopy with particular reference to low-resource situations. We determined that there is limited flexibility with regard to the utilization of PPE between ideal and low-resource settings. Some compromises are possible, especially with regard to PPE use, during endoscopic procedures. We have, therefore, also stressed the need to prevent transmission of COVID-19 by measures other than PPE and to conserve PPE by reduction of patient volume, limiting procedures to urgent or emergent, and reducing the number of staff and trainees involved in procedures. This guidance aims to optimize utilization of PPE and protection of health care providers.

The predicted impact and cost-effectiveness of systematic testing of people with incident colorectal cancer for Lynch syndrome.

OBJECTIVES: To evaluate the health impact and cost-effectiveness of systematic testing for Lynch syndrome (LS) in people with incident colorectal cancer (CRC) in Australia. DESIGN, SETTING, PARTICIPANTS: We investigated the impact of LS testing strategies in a micro-simulation model (Policy1-Lynch), explicitly modelling the cost of testing all patients diagnosed with incident CRC during 2017, with detailed modelling of outcomes for patients identified as LS carriers (probands) and their at-risk relatives throughout their lifetimes. For people with confirmed LS, we modelled ongoing colonoscopic surveillance. MAIN OUTCOME MEASURES: Cost-effectiveness of six universal tumour testing strategies (testing for DNA mismatch repair deficiencies) and of universal germline gene panel testing of patients with incident CRC; impact on cost-effectiveness of restricting testing by age at CRC diagnosis (all ages, under 50/60/70 years) and of colonoscopic surveillance interval (one, two years). RESULTS: The cost-effectiveness ratio of universal tumour testing strategies (annual colonoscopic surveillance, no testing age limit) compared with no testing ranged from $28 915 to $31 904/life-year saved (LYS) (indicative willingness-to-pay threshold: $30 000-$50 000/LYS). These strategies could avert 184-189 CRC deaths with an additional 30 597-31 084 colonoscopies over the lifetimes of 1000 patients with incident CRC with LS and 1420 confirmed LS carrier relatives (164-166 additional colonoscopies/death averted). The most cost-effective strategy was immunohistochemistry and BRAF V600E testing (incremental cost-effectiveness ratio [ICER], $28 915/LYS). Universal germline gene panel testing was not cost-effective compared with universal tumour testing strategies (ICER, $2.4 million/LYS). Immunohistochemistry and BRAF V600E testing was cost-effective at all age limits when paired with 2-yearly colonoscopic surveillance (ICER, $11 525-$32 153/LYS), and required 4778-15 860 additional colonoscopies to avert 46-181 CRC deaths (88-103 additional colonoscopies/death averted). CONCLUSIONS: Universal tumour testing strategies for guiding germline genetic testing of people with incident CRC for LS in Australia are likely to be cost-effective compared with no testing. Universal germline gene panel testing would not currently be cost-effective.

Costs and Cost-Effectiveness of Targeted, Personalized Risk Information to Increase Appropriate Screening by First-Degree Relatives of People With Colorectal Cancer.

Background. Economic evaluations are less commonly applied to implementation interventions compared to clinical interventions. The efficacy of an implementation strategy to improve adherence to screening guidelines among first-degree relatives of people with colorectal cancer was recently evaluated in a randomized-controlled trial. Using these trial data, we examined the costs and cost-effectiveness of the intervention from societal and health care funder perspectives. Method. In this prospective, trial-based evaluation, mean costs, and outcomes were calculated. The primary outcome of the trial was the proportion of participants who had screening tests in the year following the intervention commensurate with their risk category. Quality-adjusted life years were included as secondary outcomes. Intervention costs were determined from trial records. Standard Australian unit costs for 2016/2017 were applied. Cost-effectiveness was assessed using the net benefit framework. Nonparametric bootstrapping was used to calculate uncertainty intervals (UIs) around the costs and the incremental net monetary benefit statistic. Results. Compared with usual care, mean health sector costs were $17 (95% UI [$14, $24]) higher for those receiving the intervention. The incremental cost-effectiveness ratio for the primary trial outcome was calculated to be $258 (95% UI [$184, $441]) per additional person appropriately screened. The significant difference in adherence to screening guidelines between the usual care and intervention groups did not translate into a mean quality-adjusted life year difference. Discussion. Providing information on both the costs and outcomes of implementation interventions is important to inform public health care investment decisions. Challenges in the application of cost-utility analysis hampered the interpretation of results and potentially underestimated the value of the intervention. Further research in the form of a modeled extrapolation of the intermediate increased adherence effect and distributional cost-effectiveness to include equity requirements is warranted.

Revised Australian national guidelines for colorectal cancer screening: family history.

INTRODUCTION: Screening is an effective means for colorectal cancer prevention and early detection. Family history is strongly associated with colorectal cancer risk. We describe the rationale, evidence and recommendations for colorectal cancer screening by family history for people without a genetic syndrome, as reported in the 2017 revised Australian guidelines. Main recommendations: Based on 10-year risks of colorectal cancer, people at near average risk due to no or weak family history (category 1) are recommended screening by immunochemical faecal occult blood test (iFOBT) every 2 years from age 50 to 74 years. Individuals with moderate risk due to their family history (category 2) are recommended biennial iFOBT from age 40 to 49 years, then colonoscopy every 5 years from age 50 to 74 years. People with a high risk due to their family history (category 3) are recommended biennial iFOBT from age 35 to 44 years, then colonoscopy every 5 years from age 45 to 74 years. Changes in management as a result of the guidelines: By 2019, the National Bowel Cancer Screening Program will offer all Australians free biennial iFOBT screening from age 50 to 74 years, consistent with the recommendations in these guidelines for category 1. Compared with the 2005 guidelines, there are some minor changes in the family history inclusion criteria for categories 1 and 2; the genetic syndromes have been removed from category 3 and, as a consequence, colonoscopy screening is now every 5 years; and for categories 2 and 3, screening begins with iFOBT for people aged 40 and 35 years, respectively, before transitioning to colonoscopy after 10 years.

Benefits, Harms, and Cost-Effectiveness of Potential Age Extensions to the National Bowel Cancer Screening Program in Australia.

BACKGROUND: The Australian National Bowel Cancer Screening Program (NBCSP) is rolling out 2-yearly immunochemical fecal occult blood test screening in people aged 50 to 74 years. This study aimed to evaluate the benefits, harms, and cost-effectiveness of extending the NBCSP to younger and/or older ages. METHODS: A comprehensive validated microsimulation model, Policy1-Bowel, was used to simulate the fully rolled-out NBCSP and alternative strategies assuming screening starts at 40 or 45 years and/or ceases at 79 or 84 years given three scenarios: (i) perfect adherence (100%), (ii) high adherence (60%), and (ii) low adherence (40%, as currently achieved). RESULTS: The current NBCSP will reduce colorectal cancer incidence (mortality) by 23% to 51% (36% to 74%) compared with no screening (range reflects participation); extending screening to younger or older ages would result in additional reductions of 2 to 6 (2 to 9) or 1 to 3 (3 to 7) percentage points, respectively. With an indicative willingness-to-pay threshold of A$50,000/life-year saved (LYS), only screening from 50 to 74 years [incremental cost-effective ratio (ICER): A$2,984-5,981/LYS) or from 45 to 74 years (ICER: A$17,053-29,512/LYS) remained cost-effective in all participation scenarios. The number-needed-to-colonoscope to prevent a death over the lifetime of a cohort in the current NBCSP is 35 to 49. Starting screening at 45 years would increase colonoscopy demand for program-related colonoscopies by 3% to 14% and be associated with 55 to 170 additional colonoscopies per additional death prevented. CONCLUSIONS: Starting screening at 45 years could be cost-effective, but it would increase colonoscopy demand and would be associated with a less favorable incremental benefits-to-harms trade-off than screening from 50 to 74 years. IMPACT: The study underpins recently updated Australian colorectal cancer management guidelines that recommend that the NBCSP continues to offer bowel screening from 50 to 74 years.

Family history-based colorectal cancer screening in Australia: A modelling study of the costs, benefits, and harms of different participation scenarios.

BACKGROUND: The Australian National Bowel Cancer Screening Programme (NBCSP) was introduced in 2006. When fully implemented, the programme will invite people aged 50 to 74 to complete an immunochemical faecal occult blood test (iFOBT) every 2 years. METHODS AND FINDINGS: To investigate colorectal cancer (CRC) screening occurring outside of the NBCSP, we classified participants (n = 2,480) in the Australasian Colorectal Cancer Family Registry (ACCFR) into 3 risk categories (average, moderately increased, and potentially high) based on CRC family history and assessed their screening practices according to national guidelines. We developed a microsimulation to compare hypothetical screening scenarios (70% and 100% uptake) to current participation levels (baseline) and evaluated clinical outcomes and cost for each risk category. The 2 main limitations of this study are as follows: first, the fact that our cost-effectiveness analysis was performed from a third-party payer perspective, which does not include indirect costs and results in overestimated cost-effectiveness ratios, and second, that our natural history model of CRC does not include polyp sojourn time, which determines the rate of cancerous transformation. Screening uptake was low across all family history risk categories (64%-56% reported no screening). For participants at average risk, 18% reported overscreening, while 37% of those in the highest risk categories screened according to guidelines. Higher screening levels would substantially reduce CRC mortality across all risk categories (95 to 305 fewer deaths per 100,000 persons in the 70% scenario versus baseline). For those at average risk, a fully implemented NBCSP represented the most cost-effective approach to prevent CRC deaths (AUS$13,000-16,000 per quality-adjusted life year [QALY]). For those at moderately increased risk, higher adherence to recommended screening was also highly cost-effective (AUS$19,000-24,000 per QALY). CONCLUSION: Investing in public health strategies to increase adherence to appropriate CRC screening will save lives and deliver high value for money.

The use of a risk assessment and decision support tool (CRISP) compared with usual care in general practice to increase risk-stratified colorectal cancer screening: study protocol for a randomised controlled trial.

BACKGROUND: Australia and New Zealand have the highest incidence rates of colorectal cancer worldwide. In Australia there is significant unwarranted variation in colorectal cancer screening due to low uptake of the immunochemical faecal occult blood test, poor identification of individuals at increased risk of colorectal cancer, and over-referral of individuals at average risk for colonoscopy. Our pre-trial research has developed a novel Colorectal cancer RISk Prediction (CRISP) tool, which could be used to implement precision screening in primary care. This paper describes the protocol for a phase II multi-site individually randomised controlled trial of the CRISP tool in primary care. METHODS: This trial aims to test whether a standardised consultation using the CRISP tool in general practice (the CRISP intervention) increases risk-appropriate colorectal cancer screening compared to control participants who receive standardised information on cancer prevention. Patients between 50 and 74 years old, attending an appointment with their general practitioner for any reason, will be invited into the trial. A total of 732 participants will be randomised to intervention or control arms using a computer-generated allocation sequence stratified by general practice. The primary outcome (risk-appropriate screening at 12 months) will be measured using baseline data for colorectal cancer risk and objective health service data to measure screening behaviour. Secondary outcomes will include participant cancer risk perception, anxiety, cancer worry, screening intentions and health service utilisation measured at 1, 6 and 12 months post randomisation. DISCUSSION: This trial tests a systematic approach to implementing risk-stratified colorectal cancer screening in primary care, based on an individual's absolute risk, using a state-of-the-art risk assessment tool. Trial results will be reported in 2020. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry, ACTRN12616001573448p . Registered on 14 November 2016.

Evaluation of the benefits, harms and cost-effectiveness of potential alternatives to iFOBT testing for colorectal cancer screening in Australia.

The Australian National Bowel Cancer Screening Program (NBCSP) will fully roll-out 2-yearly screening using the immunochemical Faecal Occult Blood Testing (iFOBT) in people aged 50 to 74 years by 2020. In this study, we aimed to estimate the comparative health benefits, harms, and cost-effectiveness of screening with iFOBT, versus other potential alternative or adjunctive technologies. A comprehensive validated microsimulation model, Policy1-Bowel, was used to simulate a total of 13 screening approaches involving use of iFOBT, colonoscopy, sigmoidoscopy, computed tomographic colonography (CTC), faecal DNA (fDNA) and plasma DNA (pDNA), in people aged 50 to 74 years. All strategies were evaluated in three scenarios: (i) perfect adherence, (ii) high (but imperfect) adherence, and (iii) low adherence. When assuming perfect adherence, the most effective strategies involved using iFOBT (annually, or biennially with/without adjunct sigmoidoscopy either at 50, or at 54, 64 and 74 years for individuals with negative iFOBT), or colonoscopy (10-yearly, or once-off at 50 years combined with biennial iFOBT). Colorectal cancer incidence (mortality) reductions for these strategies were 51-67(74-80)% in comparison with no screening; 2-yearly iFOBT screening (i.e. the NBCSP) would be associated with reductions of 51(74)%. Only 2-yearly iFOBT screening was found to be cost-effective in all scenarios in context of an indicative willingness-to-pay threshold of A$50,000/life-year saved (LYS); this strategy was associated with an incremental cost-effectiveness ratio of A$2,984/LYS-A$5,981/LYS (depending on adherence). The fully rolled-out NBCSP is highly cost-effective, and is also one of the most effective approaches for bowel cancer screening in Australia.

Detection and staging of esophageal cancers within Barrett's esophagus is improved by assessment in specialized Barrett's units.

BACKGROUND: Identification and resection of mucosal abnormalities are critical in managing dysplastic Barrett's esophagus (BE) because these areas may harbor esophageal adenocarcinoma (EAC). OBJECTIVES: To compare mucosal lesion and EAC detection rates in dysplastic BE in the community versus a BE unit and assess the impact of EMR on disease staging and management. DESIGN: Prospective cohort study. SETTING: Tertiary referral center. PATIENTS: Patients with dysplastic BE. INTERVENTIONS: Reassessment with high-definition white-light endoscopy (HD-WLE), narrow-band imaging (NBI), and Seattle protocol biopsies. EMR performed in lesions thought to harbor neoplasia. Review of referral histology and endoscopies. MAIN OUTCOME MEASUREMENTS: Mucosal lesion and EAC detection rates in a BE unit versus the community. Impact of EMR on management. RESULTS: Sixty-nine patients were referred (88% male; median age, 69 years). At referral, HD-WLE/NBI use was 57%/14%, and Seattle protocol adherence was 20%. Eighteen patients had intramucosal cancer. Lesions were detected in 65 patients in the BE unit versus 29 patients at referral (P < .001). EMR was performed in 47 patients. BE unit assessment confirmed EAC in all 18 patients and identified 10 additional patients (56% increased cancer detection, P = .036); all 10 had lesions identified in the BE unit (vs 3 identified at referral). EMR in these patients found submucosal cancer (n = 4) and intramucosal cancer (n = 6), resulting in esophagectomy (n = 4) and chemoradiotherapy (n = 1). LIMITATION: Academic center. CONCLUSION: BE assessment at a BE unit resulted in increased lesion and EAC detection. EMR of early cancers was critical in optimizing patient management. These data suggest that BE unit referral be considered in patients with dysplastic BE.

Relationship between disease severity and quality of life and assessment of health care utilization and cost for ulcerative colitis in Australia: a cross-sectional, observational study.

BACKGROUND & AIMS: The burden of ulcerative colitis (UC) in relation to disease severity is not well documented. This study quantitatively evaluated the relationship between disease activity and quality of life (QoL), as well as health care utilization, cost, and work-related impairment associated with UC in an Australian population. METHODS: A cross-sectional, noninterventional, observational study was performed in patients with a wide range of disease severity recruited during routine specialist consultations. Evaluations included the Assessment of Quality of Life-8-dimension (AQoL-8D), EuroQol 5-dimension, 5-level (EQ-5D-5L), the disease-specific Inflammatory Bowel Disease Questionnaire (IBDQ), and the Work Productivity and Activity Impairment (WPAI) instrument. The 3-item Partial Mayo Score was used to assess disease severity. Health care resource utilization was assessed by chart review and patient questionnaires. RESULTS: In 175 patients, mean (SD) AQoL-8D and EQ-5D-5L scores were greater for patients in remission (0.80 [0.19] and 0.81 [0.18], respectively) than for patients with active disease (0.70 [0.20] and 0.72 [0.19], respectively, both Ps<0.001). IBDQ correlated with both AQoL-8D (r=0.73; P<0.0001) and EQ-5D-5L (0.69; P<0.0001). Mean 3-month UC-related health care cost per patient was AUD $2914 (SD=$3447 [mean for patients in remission=$1970; mild disease=$3736; moderate/severe disease=$4162]). Patients in remission had the least work and activity impairment. CONCLUSIONS: More severe UC disease was associated with poorer QoL. Substantial health care utilization, costs, and work productivity impairments were found in this sample of patients with UC. Moreover, greater disease activity was associated with greater health care costs and impairment in work productivity and daily activities.

Colorectal cancer risk assessment and screening recommendation: a community survey of healthcare providers' practice from a patient perspective.

BACKGROUND: Family history is a common risk factor for colorectal cancer (CRC), yet it is often underused to guide risk assessment and the provision of risk-appropriate CRC screening recommendation. The aim of this study was to identify from a patient perspective health care providers' current practice relating to: (i) assessment of family history of CRC; (ii) notification of "increased risk" to patients at "moderately/potentially high" familial risk; and (iii) recommendation that patients undertake CRC screening. METHODS: 1592 persons aged 56-88 years randomly selected from the Hunter Community Study (HCS), New South Wales, Australia were mailed a questionnaire. 1117 participants (70%) returned a questionnaire. RESULTS: Thirty eight percent of respondents reported ever being asked about their family history of CRC. Ever discussing family history of CRC with a health care provider was significantly more likely to occur for persons with a higher level of education, who had ever received screening advice and with a lower physical component summary score. Fifty one percent of persons at "moderately/potentially high risk" were notified of their "increased risk" of developing CRC. Thirty one percent of persons across each level of risk had ever received CRC screening advice from a health care provider. Screening advice provision was significantly more likely to occur for persons who had ever discussed their family history of CRC with a health care provider and who were at "moderately/potentially high risk". CONCLUSIONS: Effective interventions that integrate both the assessment and notification of familial risk of CRC to the wider population are needed. Systematic and cost-effective mechanisms that facilitate family history collection, risk assessment and provision of screening advice within the primary health care setting are required.

Improving adherence to surveillance and screening recommendations for people with colorectal cancer and their first degree relatives: a randomized controlled trial.

BACKGROUND: Colorectal cancer (CRC) is among the leading causes of cancer-related morbidity and mortality worldwide. Despite clinical practice guidelines to guide surveillance care for those who have completed treatment for this disease as well as screening for first degree relatives of people with CRC, the level of uptake of these recommendations remains uncertain. If outcomes for both patients and their families are to be improved, it is important to establish systematic and cost-effective interventions to improve adherence to guideline recommendations for CRC surveillance and screening. METHODS/DESIGN: A randomized controlled trial will be used to test the effectiveness of a print-based intervention to improve adherence to colonoscopy surveillance among people with CRC and adherence to CRC screening recommendations among their first degree relatives (FDRs). People diagnosed with CRC in the past 10 months will be recruited through a population-based cancer registry. Consenting participants will be asked if their first degree relatives might also be willing to participate in the trial. Information on family history of CRC will be obtained from patients at baseline. Patients and their families will be randomized to either minimal ethical care or the print-based intervention. The print-based intervention for FDRs will be tailored to the participant's level of risk of CRC as determined by the self-reported family history assessment. Follow up data on surveillance and screening participation will be collected from patients and their FDRs respectively at 12, 24 and 36 months' post recruitment. The primary analyses will relate to comparing levels of guideline adherence in usual care group versus print-based group in the patient sample and the FDR sample respectively. DISCUSSION: Results of this study will provide contribute to the evidence base about effective strategies to a) improve adherence to surveillance recommendation for people with CRC; and b) improve adherence to screening recommendation for FDRs of people with CRC. The use of a population-based cancer registry to access the target population may have significant advantages in increasing the reach of the intervention. TRIAL REGISTRATION: This trial is registered with the Australian and New Zealand Clinical Trials Registry Registration Number (ACTRN): ACTRN12609000628246.

How to catch all those mutations--the report of the third Human Variome Project Meeting, UNESCO Paris, May 2010.

The third Human Variome Project (HVP) Meeting "Integration and Implementation" was held under UNESCO Patronage in Paris, France, at the UNESCO Headquarters May 10-14, 2010. The major aims of the HVP are the collection, curation, and distribution of all human genetic variation affecting health. The HVP has drawn together disparate groups, by country, gene of interest, and expertise, who are working for the common good with the shared goal of pushing the boundaries of the human variome and collaborating to avoid unnecessary duplication. The meeting addressed the 12 key areas that form the current framework of HVP activities: Ethics; Nomenclature and Standards; Publication, Credit and Incentives; Data Collection from Clinics; Overall Data Integration and Access-Peripheral Systems/Software; Data Collection from Laboratories; Assessment of Pathogenicity; Country Specific Collection; Translation to Healthcare and Personalized Medicine; Data Transfer, Databasing, and Curation; Overall Data Integration and Access-Central Systems; and Funding Mechanisms and Sustainability. In addition, three societies that support the goals and the mission of HVP also held their own Workshops with the view to advance disease-specific variation data collection and utilization: the International Society for Gastrointestinal Hereditary Tumours, the Micronutrient Genomics Project, and the Neurogenetics Consortium.

Is uptake of genetic testing for colorectal cancer influenced by knowledge of insurance implications?

OBJECTIVE: To assess whether knowledge of insurance implications influenced uptake of genetic testing by participants in a research study of the causes of colorectal cancer. DESIGN, SETTING AND PARTICIPANTS: Analysis of uptake of genetic testing by participants in the population-based Victorian Colorectal Cancer Family Study during two periods: from 1999 to 2003, when participants were not informed of any potential effect of genetic testing conducted during the study on their eligibility for new insurance policies; and from 2003 to 2006, when the protocol was changed to provide participants with information on the potential effect of genetic testing on insurance eligibility. MAIN OUTCOME MEASURE: Uptake of genetic testing for germline mutations in DNA mismatch repair (MMR) genes at a family cancer clinic. RESULTS: The proportion of participants who declined genetic testing among those informed of insurance implications was more than double the proportion among those without this knowledge (29/59 [49%] v 9/47 [19%]; P = 0.002). This difference could not be explained statistically by adjusting for measured putative predictors. CONCLUSION: Identification of people with a mutation in an MMR gene has clinical importance, and such screening may be a cost-effective way to reduce the burden of colorectal cancer in the community. If people are choosing not to obtain genetic information because of how it will affect their eligibility for insurance, reforms to existing insurance practices are indicated.

Relationship between disease severity, quality of life and health-care resource use in a cross-section of Australian patients with Crohn's disease.

BACKGROUND AND AIM: New treatments for Crohn's disease are expensive and place economic strain upon health-care systems, and 'value-for-money' needs to be confirmed. This study aimed to correlate disease severity with health-related quality of life and with health-care resource use, to allow evaluation of the cost effectiveness of these treatments. METHODS: A cross-sectional, non-interventional, pharmacoeconomics study was performed with patients completing questionnaires comprising demographic, disease and health-care utilization questions, together with the disease-specific Inflammatory Bowel Disease Questionnaire (IBDQ) and the Assessment of Quality of Life (AQoL) multi-attribute utility instrument. The Crohn's Disease Activity Index (CDAI) was used to assess disease severity. RESULTS: 143 patients with a broad range of disease severity (CDAI 36-446, fistulae 23%) were recruited from referral centers. Stepwise regression analyses demonstrated a negative correlation between disease severity and both IBDQ and AQoL (both P < 0.0001). Age, gender and years since diagnosis did not impact upon either of the quality-of-life outcomes. Mean utility score for non-fistulizing patients with moderate-severe active disease (CDAI >/= 220) was 0.45, mild disease (CDAI 150-219) was 0.68 and for remission (CDAI < 150) was 0.77. Health-care resource utilization increased with increasing CDAI (P < 0.001), with hospital admissions being the largest component cost. Twenty-seven percent of patients (mean age 38 year) received a government benefit, 51% primarily due to their Crohn's disease. CONCLUSION: Crohn's disease severity correlates with poor quality of life. Utility scores determined will permit cost-utility analyses to be made in order to best allocate limited health resources.

Impact of familial adenomatous polyposis on young adults: attitudes toward genetic testing, support, and information needs.

PURPOSE: The study assessed views concerning genetic testing and information and support needs among young adults aged 18 to 35 years with a diagnosis of or at risk of developing familial adenomatous polyposis. METHODS: A total of 88 participants were recruited through Hereditary Bowel Cancer Registries and assessed using self-administered questionnaires. RESULTS: The average age of participants was 28 years, and the average age at the time of their last genetic consultation was 23 years. Although 75% would consider prenatal genetic testing, only 21% would consider termination of an affected pregnancy. Sixty-one percent selected "at birth" or "early childhood" as the preferred age for genetic testing of offspring. Participants' highest areas of unmet support needs were with regard to anxiety about their children having familial adenomatous polyposis (39%) and fear of developing cancer (28%). CONCLUSION: The parental desire to test children before it is clinically indicated may be a source of distress and create conflict with genetic services. These findings demonstrate that familial adenomatous polyposis may significantly impact young adults, with many having unmet support needs. The length of time since the last genetic consultation and the young age at which these consultations took place suggest that clinics should consider a means of regular follow-up to address these unmet needs.