The Association Between Screening for Colorectal Cancer and Mental and Physical Health.

BACKGROUND: Colorectal cancer screening reduces colorectal cancer morbidity and mortality. Identifying the factors associated with screening participation is needed to overcome barriers to screening. While several of those factors have been identified, the impact of mental and physical health on screening behaviour is not well understood. METHODS: This retrospective cohort study compared the self-reported mental and physical health of those who did screen for colorectal cancer and those who did not. Participants of the Australasian Colorectal Cancer Family Registry Cohort that were aged 45-75 years and had never been diagnosed with colorectal cancer were asked to complete a questionnaire detailing their colorectal cancer screening participation in the preceding 5 years, and a validated questionnaire of mental and physical health. Multivariable logistic regression was used to adjust for measured potential confounders. RESULTS: Of the 1130 eligible participants, 781 had a family history of colorectal cancer (69.5%), and 819 reported colorectal cancer screening in the past 5 years (72%). After adjusting for potential confounders, there was no evidence that overall mental or physical health was associated with colorectal cancer screening. However, those reporting higher levels of general health were more likely to participate in colorectal cancer screening (OR = 1.02 (100 point scale), 95% CI 1.004, 1.037, P = .014). CONCLUSION: We found limited evidence that mental and physical health were associated with colorectal cancer screening. The high proportion of participants with a family history of colorectal cancer limits the generaliseability of the findings to the general population, although we observed no differences in findings by strength of family history.

What can We Learn From High-Performing Screening Programs to Increase Bowel Cancer Screening Participation in Australia?

BACKGROUND: Colorectal cancer (CRC) is the second most diagnosed cancer in men and women and second most common cause of cancer death in Australia; Australia's CRC incidence and mortality are among the world's highest. The Australian National Bowel Cancer Screening Program began in 2006; however, only 33% of those approached for the first time by the Program between 2018 and 2019 returned the kit. Of the 5.7 million kits sent during this period, only 44% were returned. Our aim was to identify practices and features of national bowel cancer screening programs in countries with similar programs but higher screening participation, to identify potential interventions for optimising Australian CRC screening participation. METHODS: We searched published and grey literature for CRC screening programs reporting at least 50% screening participation using postal invitation and free return of iFOBT home kits. Interviews were conducted with cancer registry staff and academic researchers, focused on participant and practitioner engagement in screening. RESULTS: National programs in Netherlands, Scotland, Denmark, and Finland reported over 50% screening participation rates for all invitation rounds. Shared characteristics include small populations within small geographic areas relative to Australia; relatively high literacy; a one-sample iFOBT kit; national registration systems for population cancer screening research; and screening program research including randomised trials of program features. CONCLUSIONS: Apart from the one-sample kit, we identified no single solution to persistent Australian low uptake of screening. Research including randomised trials within the program promises to increase participation. IMPACT: This screening program comparison suggests that within-program intervention trials will lead to increased Australian screening participation.

The impact of pre-notifications and reminders on participation in colorectal cancer screening - A randomised controlled trial.

This study aimed to test whether participation in colorectal cancer (CRC) screening can be increased by combining the standard invitation procedure with a pre-notification and/or an extra reminder. In a non-blinded randomised controlled trial nested in a population-based CRC screening programme employing the faecal immunochemical test, Group I received a three-staged invitation procedure (pre-notification, invitation and one reminder), Group II received a three-staged invitation procedure (invitation and two reminders) and Group III received a four-staged invitation procedure (pre-notification, invitation and two reminders). The control group received the invitation and one reminder (usual procedure). A total of 59,041 participants were included in the analyses. Overall participation rates increased from 66.9% in the control group to 69.8% in the four-staged invitation procedure corresponding to an increase in overall participation rate of 2.9% (95% CI: 1.8 to 4.0). In the age group 50-59 years, the four-staged invitation procedure increased the participation rate by 4.0% (95% CI: 2.4 to 5.6). An extra reminder increased participation with 2.7% (95% CI: 1.1; 4.2) for males compared to 1.1% (95% CI: -0.3; 2.5) for females. In conclusion, the four-staged invitation procedure was the most effective invitation procedure indicating that multiple invitation procedures are most effective, especially in the youngest age group. If a three-staged invitation procedure is applied, a second reminder should be preferred over a pre-notification. Trial registration The project was registered at ClinicalTrials.gov on 26 February 2020 and patient enrolment began in August 2020. ClinicalTrials.gov Identifier: NCT04292366.

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.

Tumor testing to identify lynch syndrome in two Australian colorectal cancer cohorts.

BACKGROUND AND AIM: Tumor testing of colorectal cancers (CRC) for mismatch repair (MMR) deficiency is an effective approach to identify carriers of germline MMR gene mutation (Lynch syndrome). The aim of this study was to identify MMR gene mutation carriers in two cohorts of population-based CRC utilizing a combination of tumor and germline testing approaches. METHODS: Colorectal cancers from 813 patients diagnosed with CRC < 60 years of age from the Australasian Colorectal Cancer Family Registry (ACCFR) and from 826 patients from the Melbourne Collaborative Cohort Study (MCCS) were tested for MMR protein expression using immunohistochemistry, microsatellite instability (MSI), BRAFV600E somatic mutation, and for MLH1 methylation. MMR gene mutation testing (Sanger sequencing and Multiplex Ligation Dependent Probe Amplification) was performed on germline DNA of patients with MMR-deficient tumors and a subset of MMR-proficient CRCs. RESULTS: Of the 813 ACCFR probands, 90 probands demonstrated tumor MMR deficiency (11.1%), and 42 had a MMR gene germline mutation (5.2%). For the MCCS, MMR deficiency was identified in the tumors of 103 probands (12.5%) and seven had a germline mutation (0.8%). All the mutation carriers were diagnosed prior to 70 years of age. Probands with a MMR-deficient CRC without MLH1 methylation and a gene mutation were considered Lynch-like and comprised 41.1% and 25.2% of the MMR-deficient CRCs for the ACCFR and MCCS, respectively. CONCLUSIONS: Identification of MMR gene mutation carriers in Australian CRC-affected patients is optimized by immunohistochemistry screening of CRC diagnosed before 70 years of age. A significant proportion of MMR-deficient CRCs will have unknown etiology (Lynch-like) proving problematic for clinical management.

Choosing not to undergo predictive genetic testing for hereditary colorectal cancer syndromes: expanding our understanding of decliners and declining.

While medical research continues to investigate the genetic basis of cancer, and personalised prevention gains momentum, little research has been conducted with the individuals who decline predictive genetic testing for cancer. We recruited individuals who had been offered genetic testing for Lynch syndrome or bi-allelic MUTYH mutations due to their participation in a large, population-based, Australia-wide colorectal cancer study. Thirty-three individuals in mutation-carrying families, unaffected by cancer, who had actively or passively declined testing at one of four decision-making points, took part in a qualitative interview about their decision. Data analysis revealed a typology of 'decliners': (1) uninformed about genetic testing; (2) a weak intention to undergo genetic testing; (3) conditionally declining; and (4) unconditionally declining testing. In this population we found substantial barriers to achieving the benefits promised by predictive genetic testing; a lack of knowledge of the availability of genetic testing; a lack of trust in genetic test information; a desire to see a stronger benefit from genetic testing before proceeding; and a sense that there may be more negative than positive outcomes from genetic testing. These discourses must be addressed if medical research on the genetic basis of cancer continues to be funded, and personalised prevention of cancer continues to be recommended by experts.

How does genetic risk information for Lynch syndrome translate to risk management behaviours?

BACKGROUND: There is limited research on why some individuals who have undergone predictive genetic testing for Lynch syndrome do not adhere to screening recommendations. This study aimed to explore qualitatively how Lynch syndrome non-carriers and carriers translate genetic risk information and advice to decisions about risk managment behaviours in the Australian healthcare system. METHODS: Participants of the Australasian Colorectal Cancer Family Registry who had undergone predictive genetic testing for Lynch syndrome were interviewed on their risk management behaviours. Transcripts were analysed thematically using a comparative coding analysis. RESULTS: Thirty-three people were interviewed. Of the non-carriers (n = 16), 2 reported having apparently unnecessary colonoscopies, and 6 were unsure about what population-based colorectal cancer screening entails. Of the carriers (n = 17), 2 reported they had not had regular colonoscopies, and spoke about their discomfort with the screening process and a lack of faith in the procedure's ability to reduce their risk of developing colorectal cancer. Of the female carriers (n = 9), 2 could not recall being informed about the associated risk of gynaecological cancers. CONCLUSION: Non-carriers and female carriers of Lynch syndrome could benefit from further clarity and advice about appropriate risk management options. For those carriers who did not adhere to colonoscopy screening, a lack of faith in both genetic test results and screening were evident. It is essential that consistent advice is offered to both carriers and non-carriers of Lynch syndrome.

Towards quantitative condition assessment of biodiversity outcomes: Insights from Australian marine protected areas.

Protected area management effectiveness (PAME) evaluation is increasingly undertaken to evaluate governance, assess conservation outcomes and inform evidence-based management of protected areas (PAs). Within PAME, quantitative approaches to assess biodiversity outcomes are now emerging, where biological monitoring data are directly assessed against quantitative (numerically defined) condition categories (termed quantitative condition assessments). However, more commonly qualitative condition assessments are employed in PAME, which use descriptive condition categories and are evaluated largely with expert judgement that can be subject to a range of biases, such as linguistic uncertainty and overconfidence. Despite the benefits of increased transparency and repeatability of evaluations, quantitative condition assessments are rarely used in PAME. To understand why, we interviewed practitioners from all Australian marine protected area (MPA) networks, which have access to long-term biological monitoring data and are developing or conducting PAME evaluations. Our research revealed that there is a desire within management agencies to implement quantitative condition assessment of biodiversity outcomes in Australian MPAs. However, practitioners report many challenges in transitioning from undertaking qualitative to quantitative condition assessments of biodiversity outcomes, which are hampering progress. Challenges include a lack of agency capacity (staff numbers and money), knowledge gaps, and diminishing public and political support for PAs. We point to opportunities to target strategies that will assist agencies overcome these challenges, including new decision support tools, approaches to better finance conservation efforts, and to promote more management relevant science. While a single solution is unlikely to achieve full evidence-based conservation, we suggest ways for agencies to target strategies and advance PAME evaluations toward best practice.

Quantifying the utility of single nucleotide polymorphisms to guide colorectal cancer screening.

AIM: To determine whether single nucleotide polymorphisms (SNPs) can be used to identify people who should be screened for colorectal cancer. METHODS: We simulated one million people with and without colorectal cancer based on published SNP allele frequencies and strengths of colorectal cancer association. We estimated 5-year risks of colorectal cancer by number of risk alleles. RESULTS: We identified 45 SNPs with an average 1.14-fold increase colorectal cancer risk per allele (range: 1.05-1.53). The colorectal cancer risk for people in the highest quintile of risk alleles was 1.81-times that for the average person. CONCLUSION: We have quantified the extent to which known susceptibility SNPs can stratify the population into clinically useful colorectal cancer risk categories.

Perceived versus predicted risks of colorectal cancer and self-reported colonoscopies by members of mismatch repair gene mutation-carrying families who have declined genetic testing.

People carrying germline mutations in mismatch repair genes are at high risk of colorectal cancer (CRC), yet about half of people from mutation-carrying families decline genetic counselling and/or testing to identify mutation status. We studied the association of quantitative measures of risk perception, risk prediction and self-reported screening colonoscopy in this elusive yet high-risk group. The sample of 26 participants (mean age 43.1 years, 14 women) in the Australasian Colorectal Cancer Family Registry were relatives of mutation carriers; had not been diagnosed with any cancer at the time of recruitment and had declined an invitation to attend genetic counselling and/or testing. A structured elicitation protocol captured perceived CRC risk over the next 10 years. Self-reported colonoscopy screening was elicited during a 45-minute semi-structured interview. Predicted 10-year CRC risk based on age, gender, known mutation status and family history was calculated using "MMRpro." Mean perceived 10-year risk of CRC was 31 % [95 % CI 21, 40], compared with mean predicted risk of 4 % [2, 7] (p < 0.001); this was independent of age and sex (p = 0.9). Among those reporting any medical advice and any screening colonoscopy (n = 18), those with higher risk perception had less frequent colonoscopy (Pearson's r = 0.49 [0.02, 0.79]). People who decline genetic testing for CRC susceptibility mutations perceive themselves to be at substantially higher risk than they really are. Those with high perceived risk do not undertake screening colonoscopy more often than those who perceive themselves to be at average risk.

The Colorectal cancer RISk Prediction (CRISP) trial: a randomised controlled trial of a decision support tool for risk-stratified colorectal cancer screening.

BACKGROUND: A risk-stratified approach to colorectal cancer (CRC) screening could result in a more acceptable balance of benefits and harms, and be more cost-effective. AIM: To determine the effect of a consultation in general practice using a computerised risk assessment and decision support tool (Colorectal cancer RISk Prediction, CRISP) on risk-appropriate CRC screening. DESIGN AND SETTING: Randomised controlled trial in 10 general practices in Melbourne, Australia, from May 2017 to May 2018. METHOD: Participants were recruited from a consecutive sample of patients aged 50-74 years attending their GP. Intervention consultations included CRC risk assessment using the CRISP tool and discussion of CRC screening recommendations. Control group consultations focused on lifestyle CRC risk factors. The primary outcome was risk-appropriate CRC screening at 12 months. RESULTS: A total of 734 participants (65.1% of eligible patients) were randomised (369 intervention, 365 control); the primary outcome was determined for 722 (362 intervention, 360 control). There was a 6.5% absolute increase (95% confidence interval [CI] = -0.28 to 13.2) in risk-appropriate screening in the intervention compared with the control group (71.5% versus 65.0%; odds ratio [OR] 1.36, 95% CI = 0.99 to 1.86, P = 0.057). In those due CRC screening during follow-up, there was a 20.3% (95% CI = 10.3 to 30.4) increase (intervention 59.8% versus control 38.9%; OR 2.31, 95% CI = 1.51 to 3.53, P<0.001) principally by increasing faecal occult blood testing in those at average risk. CONCLUSION: A risk assessment and decision support tool increases risk-appropriate CRC screening in those due screening. The CRISP intervention could commence in people in their fifth decade to ensure people start CRC screening at the optimal age with the most cost-effective test.

Screening practices of Australian men and women categorized as "at or slightly above average risk" of colorectal cancer.

PURPOSE: Australia has one of the highest incidences of colorectal cancer (CRC) in the world. In 2006, the federal government introduced a screening program consisting of a one-off fecal occult blood test offered to people turning 50, 55, or 65 years. We conducted a population-based study to estimate CRC screening practices existing outside the current program. METHODS: A total of 1887 unaffected subjects categorized "at or slightly above average risk" of CRC were selected from the Australasian Colorectal Cancer Family Registry. We calculated the proportions of participants that reported appropriate, under- and over-screening according to national guidelines. We performed a logistic regression analysis to evaluate associations between over-screening and a set of socio-demographic factors. RESULTS: Of 532 participants at average risk of CRC, eligible for screening, 4 (0.75 %) reported appropriate screening, 479 (90 %) reported never having been screened, 18 (3 %) reported some but less than appropriate screening, and 31 (6 %) reported over-screening. Of 412 participants aged 50 years or over, slightly above average risk of CRC, 1 participant (0.25 %) reported appropriate screening, 316 (77 %) reported no screening, and 11 (3 %) reported some but less than appropriate screening. Among participants under age 50 years, 2 % of those at average risk and 10 % of those slightly above average risk reported over-screening. Middle-aged people, those with a family history of CRC and those with a university degree, were more likely to be over-screened. CONCLUSION: Overall, the level of CRC screening participation was low and the vast majority of screening tests undertaken were inappropriate in terms of timing, modality, or frequency.

Reducing overconfidence in the interval judgments of experts.

Elicitation of expert opinion is important for risk analysis when only limited data are available. Expert opinion is often elicited in the form of subjective confidence intervals; however, these are prone to substantial overconfidence. We investigated the influence of elicitation question format, in particular the number of steps in the elicitation procedure. In a 3-point elicitation procedure, an expert is asked for a lower limit, upper limit, and best guess, the two limits creating an interval of some assigned confidence level (e.g., 80%). In our 4-step interval elicitation procedure, experts were also asked for a realistic lower limit, upper limit, and best guess, but no confidence level was assigned; the fourth step was to rate their anticipated confidence in the interval produced. In our three studies, experts made interval predictions of rates of infectious diseases (Study 1, n = 21 and Study 2, n = 24: epidemiologists and public health experts), or marine invertebrate populations (Study 3, n = 34: ecologists and biologists). We combined the results from our studies using meta-analysis, which found average overconfidence of 11.9%, 95% CI [3.5, 20.3] (a hit rate of 68.1% for 80% intervals)-a substantial decrease in overconfidence compared with previous studies. Studies 2 and 3 suggest that the 4-step procedure is more likely to reduce overconfidence than the 3-point procedure (Cohen's d = 0.61, [0.04, 1.18]).

Discussions about predictive genetic testing for Lynch syndrome: the role of health professionals and families in decisions to decline.

Unaffected relatives of individuals with Lynch syndrome can be offered predictive genetic testing to guide surveillance recommendations. The decision-making process of those who decline testing, particularly those who do not attend a clinical genetics service, is poorly understood. We have addressed this gap by interviewing 33 individuals from Lynch syndrome mutation-carrying families, unaffected by cancer, who declined predictive genetic testing. Here, we analyse the data provided by 20 participants who unequivocally declined testing. Those who indicated they did not have enough information to make a decision or intended to undergo testing in the future were excluded. Analysis revealed that few decliners discussed their decision with general practitioners or genetic counsellors. Family members were commonly involved to varying degrees, with participants either (1) making group decisions with family members, (2) feeling persuaded by family members to either accept or decline testing, (3) discussing the test but making their own decision. A minority did not discuss testing with family members while making their decision. This research reveals the health communication activities of an understudied group, those declining predictive testing, and indicates that for many, health professionals play a minor role in the decision compared to family.

The CRISP-Q study: Communicating the risks and benefits of colorectal cancer screening

Background and objectives: Many Australians at average risk of colorectal cancer (CRC) are undergoing unnecessary colonoscopic screening, while many at increased risk are getting inadequate screening. The aim of this study was to test different ways of communicating the risks and benefits of CRC screening, as part of the development of a CRC risk prediction (CRISP) tool. Method: General practice patients were shown five different risk presentations for hypothetical 'average' and 'increased' risk cases and were asked to choose the screening method they would undergo. Associations were explored between risk presentation type and 'risk-appropriate screening' choice. Results: All risk formats were associated with improved risk-appropriate screening by participants (n = 204); however, there was a statistical trend favouring absolute risk with a government recommendation and an 'expected frequency tree'. The icon array was most weakly associated with appropriate screening. Discussion: This research will inform approaches to communicating risk in CRISP and may be of wider relevance to supporting informed decisions about cancer screening.

Twin studies for the prognosis, prevention and treatment of musculoskeletal conditions.

BACKGROUND: Musculoskeletal conditions are highly prevalent in our ageing society and are therefore incurring substantial increases in population levels of years lived with disability (YLD). An evidence-based approach to the prognosis, prevention, and treatment of those disorders can allow an overall improvement in the quality of life of patients, while also softening the burden on national health care systems. METHODS: In this Masterclass article, we provide an overview of the most relevant twin study designs, their advantages, limitations and major contributions to the investigation of traits related to the domain of musculoskeletal physical therapy. CONCLUSIONS: Twin studies can be an important scientific tool to address issues related to musculoskeletal conditions. They allow researchers to understand how genes and environment combine to influence human health and disease. Twin registries and international collaboration through existing networks can provide resources for achieving large sample sizes and access to expertise in study design and analysis of twin data.

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.

Twin birth changes DNA methylation of subsequent siblings.

We asked if twin birth influences the DNA methylation of subsequent siblings. We measured whole blood methylation using the HumanMethylation450 array for siblings from two twin and family studies in Australia and Korea. We compared the means and correlations in methylation between pairs of siblings born before a twin birth (BT siblings), born on either side of a twin birth (B/AT pairs) and born after a twin birth (AT siblings). For the genome-wide average DNA methylation, the correlation for AT pairs (rAT) was larger than the correlation for BT pairs (rBT) in both studies, and from the meta-analysis, rAT = 0.46 (95% CI: 0.26, 0.63) and rBT = -0.003 (95% CI: -0.30, 0.29) (P = 0.02). B/AT pairs were not correlated (from the meta-analysis rBAT = 0.08; 95% CI: -0.31, 0.45). Similar results were found for the average methylation of several genomic regions, e.g., CpG shelf and gene body. BT and AT pairs were differentially correlated in methylation for 15 probes (all P < 10-7), and the top 152 differentially correlated probes (at P < 10-4) were enriched in cell signalling and breast cancer regulation pathways. Our observations are consistent with a twin birth changing the intrauterine environment such that siblings both born after a twin birth are correlated in DNA methylation.

The Impact of Receiving Predictive Genetic Information about Lynch Syndrome on Individual Colonoscopy and Smoking Behaviors.

BACKGROUND: This study investigated whether receiving the results of predictive genetic testing for Lynch syndrome, indicating the presence or absence of an inherited predisposition to various cancers, including colorectal cancer, was associated with change in individual colonoscopy and smoking behaviors, which could prevent colorectal cancer. METHODS: The study population included individuals with no previous diagnosis of colorectal cancer, whose families had already identified deleterious mutations in the mismatch repair or EPCAM genes. Hypotheses were generated from a simple health economics model and tested against individual-level panel data from the Australasian Colorectal Cancer Family Registry. RESULTS: The empirical analysis revealed evidence consistent with some of the hypotheses, with a higher likelihood of undergoing colonoscopy in those who discovered their genetic predisposition to colorectal cancer and a lower likelihood of quitting smoking in those who discovered their lack thereof. CONCLUSIONS: Predictive genetic information about Lynch syndrome was associated with change in individual colonoscopy and smoking behaviors but not necessarily in ways to improve population health. IMPACT: The study findings suggest that the impact of personalized medicine on disease prevention is intricate, warranting further analyses to determine the net benefits and costs. Cancer Epidemiol Biomarkers Prev; 25(11); 1524-33. ©2016 AACR.

The relationship between naloxone dose and key patient variables in the treatment of non-fatal heroin overdose in the prehospital setting.

OBJECTIVES: To examine the relationship between key patient variables and variation in naloxone dose (from the standard dose of 1.6 mg IMI) administered by ambulance paramedics in the prehospital management of heroin overdose. METHODS: A retrospective analysis of 7985 ambulance patient care records of non-fatal heroin overdose cases collected in greater metropolitan Melbourne. The main outcome measure was the dose of intramuscular naloxone required to increase the level of consciousness and the respiratory rate in patients presenting with suspected heroin overdose. Key patient variables influencing the dose that were recorded included: age, sex, initial patient presentation and reported concurrent alcohol use. RESULTS: Multinomial logistic regression revealed that patients with higher levels of consciousness and respiratory rates on arrival of the paramedic crew were more likely to receive a less than standard dose of naloxone. Conversely, patients with lower levels of consciousness and low respiratory rates received greater than standard doses of naloxone for resuscitation. Patients who received greater than the standard dose of naloxone were 2.25 (95% CI, 1.83-2.77) times more likely to have been under the influence of alcohol when consuming the heroin that resulted in overdose. CONCLUSIONS: The concurrent use of alcohol with heroin resulted in the use of greater than standard doses of naloxone by paramedics in resuscitating overdose patients. It is possible that the higher dose of naloxone is required to reverse the combined effects of alcohol and heroin. There was also a link between initial patient presentation and the dose of naloxone required for resuscitation. In light of these findings, it would appear that initial patient presentation and evidence of alcohol use might be useful guides as to providing the most effective dose of naloxone in the prehospital setting.