Use of chemotherapy in patients with oesophageal, stomach, colon, rectal, liver, pancreatic, lung, and ovarian cancer: an International Cancer Benchmarking Partnership (ICBP) population-based study.

BACKGROUND: There are few data on international variation in chemotherapy use, despite it being a key treatment type for some patients with cancer. Here, we aimed to examine the presence and size of such variation. METHODS: This population-based study used data from Norway, the four UK nations (England, Northern Ireland, Scotland, and Wales), eight Canadian provinces (Alberta, British Columbia, Manitoba, Newfoundland and Labrador, Nova Scotia, Ontario, Prince Edward Island, and Saskatchewan), and two Australian states (New South Wales and Victoria). Patients aged 15-99 years diagnosed with cancer in eight different sites (oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer), with no other primary cancer diagnosis occurring from within the 5 years before to 1 year after the index cancer diagnosis or during the study period were included in the study. We examined variation in chemotherapy use from 31 days before to 365 days after diagnosis and time to its initiation, alongside related variation in patient group differences. Information was obtained from cancer registry records linked to clinical or patient management system data or hospital administration data. Random-effects meta-analyses quantified interjurisdictional variation using 95% prediction intervals (95% PIs). FINDINGS: Between Jan 1, 2012, and Dec 31, 2017, of 893 461 patients with a new diagnosis of one of the studied cancers, 111 569 (12·5%) did not meet the inclusion criteria, and 781 892 were included in the analysis. There was large interjurisdictional variation in chemotherapy use for all studied cancers, with wide 95% PIs: 47·5 to 81·2 (pooled estimate 66·4%) for ovarian cancer, 34·9 to 59·8 (47·2%) for oesophageal cancer, 22·3 to 62·3 (40·8%) for rectal cancer, 25·7 to 55·5 (39·6%) for stomach cancer, 17·2 to 56·3 (34·1%) for pancreatic cancer, 17·9 to 49·0 (31·4%) for lung cancer, 18·6 to 43·8 (29·7%) for colon cancer, and 3·5 to 50·7 (16·1%) for liver cancer. For patients with stage 3 colon cancer, the interjurisdictional variation was greater than that for all patients with colon cancer (95% PI 38·5 to 78·4; 60·1%). Patients aged 85-99 years had 20-times lower odds of chemotherapy use than those aged 65-74 years, with very large interjurisdictional variation in this age difference (odds ratio 0·05; 95% PI 0·01 to 0·19). There was large variation in median time to first chemotherapy (from diagnosis date) by cancer site, with substantial interjurisdictional variation, particularly for rectal cancer (95% PI -15·5 to 193·9 days; pooled estimate 89·2 days). Patients aged 85-99 years had slightly shorter median time to first chemotherapy compared with those aged 65-74 years, consistently between jurisdictions (-3·7 days, 95% PI -7·6 to 0·1). INTERPRETATION: Large variation in use and time to chemotherapy initiation were observed between the participating jurisdictions, alongside large and variable age group differences in chemotherapy use. To guide efforts to improve patient outcomes, the underlying reasons for these patterns need to be established. FUNDING: International Cancer Benchmarking Partnership (funded by the Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, The Cancer Society of New Zealand, National Health Service England, Norwegian Cancer Society, Public Health Agency Northern Ireland on behalf of the Northern Ireland Cancer Registry, DG Health and Social Care Scottish Government, Western Australia Department of Health, and Public Health Wales NHS Trust).

Use of radiotherapy in patients with oesophageal, stomach, colon, rectal, liver, pancreatic, lung, and ovarian cancer: an International Cancer Benchmarking Partnership (ICBP) population-based study.

BACKGROUND: There is little evidence on variation in radiotherapy use in different countries, although it is a key treatment modality for some patients with cancer. Here we aimed to examine such variation. METHODS: This population-based study used data from Norway, the four UK nations (England, Northern Ireland, Scotland, and Wales), nine Canadian provinces (Alberta, British Columbia, Manitoba, New Brunswick, Newfoundland and Labrador, Nova Scotia, Ontario, Prince Edward Island, and Saskatchewan), and two Australian states (New South Wales and Victoria). Patients aged 15-99 years diagnosed with cancer in eight different sites (oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer), with no other primary cancer diagnosis occurring within the 5 years before to 1 year after the index cancer diagnosis or during the study period were included in the study. We examined variation in radiotherapy use from 31 days before to 365 days after diagnosis and time to its initiation, alongside related variation in patient group differences. Information was obtained from cancer registry records linked to clinical or patient management system data, or hospital administration data. Random-effects meta-analyses quantified interjurisdictional variation using 95% prediction intervals (95% PIs). FINDINGS: Between Jan 1, 2012, and Dec 31, 2017, of 902 312 patients with a new diagnosis of one of the studied cancers, 115 357 (12·8%) did not meet inclusion criteria, and 786,955 were included in the analysis. There was large interjurisdictional variation in radiotherapy use, with wide 95% PIs: 17·8 to 82·4 (pooled estimate 50·2%) for oesophageal cancer, 35·5 to 55·2 (45·2%) for rectal cancer, 28·6 to 54·0 (40·6%) for lung cancer, and 4·6 to 53·6 (19·0%) for stomach cancer. For patients with stage 2-3 rectal cancer, interjurisdictional variation was greater than that for all patients with rectal cancer (95% PI 37·0 to 84·6; pooled estimate 64·2%). Radiotherapy use was infrequent but variable in patients with pancreatic (95% PI 1·7 to 16·5%), liver (1·8 to 11·2%), colon (1·6 to 5·0%), and ovarian (0·8 to 7·6%) cancer. Patients aged 85-99 years had three-times lower odds of radiotherapy use than those aged 65-74 years, with substantial interjurisdictional variation in this age difference (odds ratio [OR] 0·38; 95% PI 0·20-0·73). Women had slightly lower odds of radiotherapy use than men (OR 0·88, 95% PI 0·77-1·01). There was large variation in median time to first radiotherapy (from diagnosis date) by cancer site, with substantial interjurisdictional variation (eg, oesophageal 95% PI 11·3 days to 112·8 days; pooled estimate 62·0 days; rectal 95% PI 34·7 days to 77·3 days; pooled estimate 56·0 days). Older patients had shorter median time to radiotherapy with appreciable interjurisdictional variation (-9·5 days in patients aged 85-99 years vs 65-74 years, 95% PI -26·4 to 7·4). INTERPRETATION: Large interjurisdictional variation in both use and time to radiotherapy initiation were observed, alongside large and variable age differences. To guide efforts to improve patient outcomes, underlying reasons for these differences need to be established. FUNDING: International Cancer Benchmarking Partnership (funded by the Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, The Cancer Society of New Zealand, National Health Service England, Norwegian Cancer Society, Public Health Agency Northern Ireland on behalf of the Northern Ireland Cancer Registry, DG Health and Social Care Scottish Government, Western Australia Department of Health, and Public Health Wales NHS Trust).

Risk factors and prognostic implications of diagnosis of cancer within 30 days after an emergency hospital admission (emergency presentation): an International Cancer Benchmarking Partnership (ICBP) population-based study.

BACKGROUND: Greater understanding of international cancer survival differences is needed. We aimed to identify predictors and consequences of cancer diagnosis through emergency presentation in different international jurisdictions in six high-income countries. METHODS: Using a federated analysis model, in this cross-sectional population-based study, we analysed cancer registration and linked hospital admissions data from 14 jurisdictions in six countries (Australia, Canada, Denmark, New Zealand, Norway, and the UK), including patients with primary diagnosis of invasive oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer during study periods from Jan 1, 2012, to Dec 31, 2017. Data were collected on cancer site, age group, sex, year of diagnosis, and stage at diagnosis. Emergency presentation was defined as diagnosis of cancer within 30 days after an emergency hospital admission. Using logistic regression, we examined variables associated with emergency presentation and associations between emergency presentation and short-term mortality. We meta-analysed estimates across jurisdictions and explored jurisdiction-level associations between cancer survival and the percentage of patients diagnosed as emergencies. FINDINGS: In 857 068 patients across 14 jurisdictions, considering all of the eight cancer sites together, the percentage of diagnoses through emergency presentation ranged from 24·0% (9165 of 38 212 patients) to 42·5% (12 238 of 28 794 patients). There was consistently large variation in the percentage of emergency presentations by cancer site across jurisdictions. Pancreatic cancer diagnoses had the highest percentage of emergency presentations on average overall (46·1% [30 972 of 67 173 patients]), with the jurisdictional range being 34·1% (1083 of 3172 patients) to 60·4% (1317 of 2182 patients). Rectal cancer had the lowest percentage of emergency presentations on average overall (12·1% [10 051 of 83 325 patients]), with a jurisdictional range of 9·1% (403 of 4438 patients) to 19·8% (643 of 3247 patients). Across the jurisdictions, older age (ie, 75-84 years and 85 years or older, compared with younger patients) and advanced stage at diagnosis compared with non-advanced stage were consistently associated with increased emergency presentation risk, with the percentage of emergency presentations being highest in the oldest age group (85 years or older) for 110 (98%) of 112 jurisdiction-cancer site strata, and in the most advanced (distant spread) stage category for 98 (97%) of 101 jurisdiction-cancer site strata with available information. Across the jurisdictions, and despite heterogeneity in association size (I2=93%), emergency presenters consistently had substantially greater risk of 12-month mortality than non-emergency presenters (odds ratio >1·9 for 112 [100%] of 112 jurisdiction-cancer site strata, with the minimum lower bound of the related 95% CIs being 1·26). There were negative associations between jurisdiction-level percentage of emergency presentations and jurisdiction-level 1-year survival for colon, stomach, lung, liver, pancreatic, and ovarian cancer, with a 10% increase in percentage of emergency presentations in a jurisdiction being associated with a decrease in 1-year net survival of between 2·5% (95% CI 0·28-4·7) and 7·0% (1·2-13·0). INTERPRETATION: Internationally, notable proportions of patients with cancer are diagnosed through emergency presentation. Specific types of cancer, older age, and advanced stage at diagnosis are consistently associated with an increased risk of emergency presentation, which strongly predicts worse prognosis and probably contributes to international differences in cancer survival. Monitoring emergency presentations, and identifying and acting on contributing behavioural and health-care factors, is a global priority for cancer control. FUNDING: Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Cancer Society of New Zealand; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; the Scottish Government; Western Australia Department of Health; and Wales Cancer Network.

Colon and rectal cancer survival in seven high-income countries 2010-2014: variation by age and stage at diagnosis (the ICBP SURVMARK-2 project).

OBJECTIVES: As part of the International Cancer Benchmarking Partnership (ICBP) SURVMARK-2 project, we provide the most recent estimates of colon and rectal cancer survival in seven high-income countries by age and stage at diagnosis. METHODS: Data from 386 870 patients diagnosed during 2010-2014 from 19 cancer registries in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK) were analysed. 1-year and 5-year net survival from colon and rectal cancer were estimated by stage at diagnosis, age and country, RESULTS: (One1-year) and 5-year net survival varied between (77.1% and 87.5%) 59.1% and 70.9% and (84.8% and 90.0%) 61.6% and 70.9% for colon and rectal cancer, respectively. Survival was consistently higher in Australia, Canada and Norway, with smaller proportions of patients with metastatic disease in Canada and Australia. International differences in (1-year) and 5-year survival were most pronounced for regional and distant colon cancer ranging between (86.0% and 94.1%) 62.5% and 77.5% and (40.7% and 56.4%) 8.0% and 17.3%, respectively. Similar patterns were observed for rectal cancer. Stage distribution of colon and rectal cancers by age varied across countries with marked survival differences for patients with metastatic disease and diagnosed at older ages (irrespective of stage). CONCLUSIONS: Survival disparities for colon and rectal cancer across high-income countries are likely explained by earlier diagnosis in some countries and differences in treatment for regional and distant disease, as well as older age at diagnosis. Differences in cancer registration practice and different staging systems across countries may have impacted the comparisons.

Progress in cancer survival, mortality, and incidence in seven high-income countries 1995-2014 (ICBP SURVMARK-2): a population-based study.

BACKGROUND: Population-based cancer survival estimates provide valuable insights into the effectiveness of cancer services and can reflect the prospects of cure. As part of the second phase of the International Cancer Benchmarking Partnership (ICBP), the Cancer Survival in High-Income Countries (SURVMARK-2) project aims to provide a comprehensive overview of cancer survival across seven high-income countries and a comparative assessment of corresponding incidence and mortality trends. METHODS: In this longitudinal, population-based study, we collected patient-level data on 3·9 million patients with cancer from population-based cancer registries in 21 jurisdictions in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway, and the UK) for seven sites of cancer (oesophagus, stomach, colon, rectum, pancreas, lung, and ovary) diagnosed between 1995 and 2014, and followed up until Dec 31, 2015. We calculated age-standardised net survival at 1 year and 5 years after diagnosis by site, age group, and period of diagnosis. We mapped changes in incidence and mortality to changes in survival to assess progress in cancer control. FINDINGS: In 19 eligible jurisdictions, 3 764 543 cases of cancer were eligible for inclusion in the study. In the 19 included jurisdictions, over 1995-2014, 1-year and 5-year net survival increased in each country across almost all cancer types, with, for example, 5-year rectal cancer survival increasing more than 13 percentage points in Denmark, Ireland, and the UK. For 2010-14, survival was generally higher in Australia, Canada, and Norway than in New Zealand, Denmark, Ireland, and the UK. Over the study period, larger survival improvements were observed for patients younger than 75 years at diagnosis than those aged 75 years and older, and notably for cancers with a poor prognosis (ie, oesophagus, stomach, pancreas, and lung). Progress in cancer control (ie, increased survival, decreased mortality and incidence) over the study period was evident for stomach, colon, lung (in males), and ovarian cancer. INTERPRETATION: The joint evaluation of trends in incidence, mortality, and survival indicated progress in four of the seven studied cancers. Cancer survival continues to increase across high-income countries; however, international disparities persist. While truly valid comparisons require differences in registration practice, classification, and coding to be minimal, stage of disease at diagnosis, timely access to effective treatment, and the extent of comorbidity are likely the main determinants of patient outcomes. Future studies are needed to assess the impact of these factors to further our understanding of international disparities in cancer survival. FUNDING: Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Cancer Society of New Zealand; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; The Scottish Government; Western Australia Department of Health; and Wales Cancer Network.

Diagnostic validation of three test methods for detection of cyprinid herpesvirus 3 (CyHV-3).

Cyprinid herpesvirus 3 (CyHV-3) is the aetiological agent of koi herpesvirus disease in koi and common carp. The disease is notifiable to the World Organisation for Animal Health. Three tests-quantitative polymerase chain reaction (qPCR), conventional PCR (cPCR) and virus isolation by cell culture (VI)-were validated to assess their fitness as diagnostic tools for detection of CyHV-3. Test performance metrics of diagnostic accuracy were sensitivity (DSe) and specificity (DSp). Repeatability and reproducibility were measured to assess diagnostic precision. Estimates of test accuracy, in the absence of a gold standard reference test, were generated using latent class models. Test samples originated from wild common carp naturally exposed to CyHV-3 or domesticated koi either virus free or experimentally infected with the virus. Three laboratories in Canada participated in the precision study. Moderate to high repeatability (81 to 99%) and reproducibility (72 to 97%) were observed for the qPCR and cPCR tests. The lack of agreement observed between some of the PCR test pair results was attributed to cross-contamination of samples with CyHV-3 nucleic acid. Accuracy estimates for the PCR tests were 99% for DSe and 93% for DSp. Poor precision was observed for the VI test (4 to 95%). Accuracy estimates for VI/qPCR were 90% for DSe and 88% for DSp. Collectively, the results show that the CyHV-3 qPCR test is a suitable tool for surveillance, presumptive diagnosis and certification of individuals or populations as CyHV-3 free.

Use of emergency departments and primary care visits for asthma related conditions in the 3 years following an asthma education program.

BACKGROUND: This study examines changes in Primary Care Visits (PCVs) and Emergency Department Visits (EDVs) among 1918 patients with asthma who attended either two visits, one visit or were no-show referrals at the Dr. Patrick Gill Asthma Education Center (AEC) in Charlottetown Prince Edward Island (PEI) between January 1, 2003 and March 31, 2008 compared to 2799 controls selected from a list of PEI asthma patients developed for the Canadian Chronic Disease Surveillance System (CCDSS). METHODS: Hurdle regression was used to model counts of PCVs and negative binomial models were used to model counts of EDVs at 12 months prior to AEC contact and 0-1, >1 to 2 and >2 to 3 years after AEC contact. The PEI Research Board approved the project. RESULTS: No-show referrals had a significant increase in pediatric EDVs and PCVs in the first year after referral. The higher rates of PCVs and EDVs prior to contact with the AEC in patients referred to the AEC were reduced after contact with the AEC, although they remained significantly higher than the CCDSS controls. CONCLUSIONS: Compared to patients who attended the AEC, referred patients who did not attend the AEC did not achieve similar reductions in pediatric EDVs and PCVs in the first year after referral.

Mapping Canadian Data Assets to Generate Real-World Evidence: Lessons Learned from Canadian Real-World Evidence for Value of Cancer Drugs (CanREValue) Collaboration's RWE Data Working Group.

Canadian provinces routinely collect patient-level data for administrative purposes. These real-world data (RWD) can be used to generate real-world evidence (RWE) to inform clinical care and healthcare policy. The CanREValue Collaboration is developing a framework for the use of RWE in cancer drug funding decisions. A Data Working Group (WG) was established to identify data assets across Canada for generating RWE of oncology drugs. The mapping exercise was conducted using an iterative scan with informant surveys and teleconference. Data experts from ten provinces convened for a total of three teleconferences and two in-person meetings from March 2018 to September 2019. Following each meeting, surveys were developed and shared with the data experts which focused on identifying databases and data elements, as well as a feasibility assessment of conducting RWE studies using existing data elements and resources. Survey responses were compiled into an interim data report, which was used for public stakeholder consultation. The feedback from the public consultation was used to update the interim data report. We found that databases required to conduct real-world studies are often held by multiple different data custodians. Ninety-seven databases were identified across Canada. Provinces held on average 9 distinct databases (range: 8-11). An Essential RWD Table was compiled that contains data elements that are necessary, at a minimal, to conduct an RWE study. An Expanded RWD Table that contains a more comprehensive list of potentially relevant data elements was also compiled and the availabilities of these data elements were mapped. While most provinces have data on patient demographics (e.g., age, sex) and cancer-related variables (e.g., morphology, topography), the availability and linkability of data on cancer treatment, clinical characteristics (e.g., morphology and topography), and drug costs vary among provinces. Based on current resources, data availability, and access processes, data experts in most provinces noted that more than 12 months would be required to complete an RWE study. The CanREValue Collaboration's Data WG identified key data holdings, access considerations, as well as gaps in oncology treatment-specific data. This data catalogue can be used to facilitate future oncology-specific RWE analyses across Canada.

Development and validation of a reverse transcription quantitative PCR for universal detection of viral hemorrhagic septicemia virus.

Viral hemorrhagic septicemia virus (VHSV) infects over 70 fish species inhabiting marine, brackish or freshwater environments throughout the Northern Hemisphere. Over its geographic range, 4 VHSV genotypes and multiple subtypes exist. Here, we describe the development and validation of a rapid, sensitive and specific real-time reverse transcription quantitative PCR assay (RT-qPCR) that amplifies sequence from representative isolates of all VHSV genotypes (I, II, III and IV). The pan-specific VHSV RT-qPCR assay reliably detects 100 copies of VHSV nucleoprotein RNA without cross-reacting with infectious hematopoietic necrosis virus, spring viremia of carp virus or aquatic birnavirus. Test performance characteristics evaluated on experimentally infected Atlantic salmon Salmo salar L. revealed a diagnostic sensitivity (DSe) > or = 93% and specificity (DSp) = 100%. The repeatability and reproducibility of the procedure was exceptionally high, with 93% agreement among test results within and between 2 laboratories. Furthermore, proficiency testing demonstrated the VHSV RT-qPCR assay to be easily transferred to and performed by a total of 9 technicians representing 4 laboratories in 2 countries. The assay performed equivalent to the traditional detection method of virus isolation via cell culture with the advantage of faster turnaround times and high throughput capacity, further suggesting the suitability of the use of this VHSV RT-qPCR in a diagnostic setting.

Bayesian latent class model estimates of diagnostic accuracy for three test methods designed to detect spring viremia of carp virus.

Spring viremia of carp virus (SVCV) causes a systemic hemorrhagic disease that poses a significant risk to wild and cultured fish and is listed as notifiable by the World Organization for Animal Health. Validated molecular diagnostic tools for SVCV are required to accurately describe and analyze the ecology of the virus. Here, the diagnostic specificity (DSp) and sensitivity (DSe) (i.e. accuracy) of three SVCV diagnostic tests - 2 reverse transcription quantitative polymerase chain reaction (RT-qPCR) assays Q1G and Q2N and virus isolation by cell culture (VI) - were evaluated using 2-class latent class models run in maximum likelihood (ML) and Bayesian frameworks. Virus-free or experimentally-infected koi were sorted into three populations with low, moderate or high prevalence levels of SVCV (n = 269 fish in total). Koi kidney tissues were tested using Q2N and Q1G and for the VI assay, pools of kidney, spleen and gill tissues were used. All samples were blinded and analyzed in one laboratory. The ML and Bayesian approaches successfully estimated the diagnostic accuracy of the 3 tests with the exception of 1 ML model. The estimates were consistent across the two frameworks. The DSe estimates were higher for Q1G (>98 %) and Q2N (>96 %) compared to VI (>60 %). The DSp of all three tests varied by 12-15 % (79-91 % for Q1G, 79-94 % for Q2N and 81-97 % for VI) across same-fish samples revealing the potential range in test performance for one sample. The 3 fish populations had distinct SVCV prevalence levels estimated at 0-3 % (low), 70-73 % (moderate) and 95-96 % (high). The Bayesian covariance models revealed minor DSe dependence between Q1G and Q2N. The results suggested that SVCV diagnostic tests Q2N and Q1G are suitable for use as diagnostic assays and are fit for presumptive diagnosis, surveillance, and certification of populations or individuals as SVCV free.

Measures of diagnostic precision (repeatability and reproducibility) for three test methods designed to detect spring viremia of carp virus.

Spring viremia of carp virus (SVCV) is a rhabdovirus of the Sprivivirus genus and the etiological agent of an internationally regulated aquatic animal disease in several fish species, including koi carp Cyprinus carpio L. The virus has a complex lifecycle with both acute and persistent stages of infection and can cause high mortality in affected populations. In this study, the diagnostic repeatability (within laboratory agreement) and reproducibility (between laboratory agreement) of 3 tests were investigated to assess their fitness as SVCV diagnostic tools. The tests, reverse transcription quantitative polymerase chain reaction (RT-qPCR) assays targeting either the SVCV glycoprotein (Q1G) or nucleoprotein (Q2N) genes and virus isolation by cell culture (VI), were performed in a blinded study with four Canadian laboratories. Test panels consisted of duplicate sets of 100 tissue samples collected from 3 SVCV prevalence populations of koi: a low-prevalence negative reference population (n = 20 fish) as well as moderate- (n = 50 fish) and high-prevalence (n = 30 fish) populations of koi experimentally infected with SVCV. The Q1G and Q2N tests were performed with kidney tissue in 3 laboratories and with brain tissue in 1 laboratory whereas pools of kidney, spleen and gill tissues were tested with the VI assay in 2 laboratories. Agreement of binary results was evaluated using the observed proportion of agreement, Cohen's kappa and Gwet's agreement coefficient (AC1) whereas the concordance correlation coefficient (ccc) and Bland Altman's limit of agreement were used to evaluate agreement of the RT-qPCR continuous data. Gwet's AC1 provided a more stable estimate of agreement than Cohen's kappa. Overall, high repeatability (AC1, 0.78-0.90) and reproducibility (AC1, 0.74-0.89) were observed for the Q1G and Q2N tests when kidney tissue was used. Lower agreement estimates of repeatability (AC1, 0.54-0.77) and reproducibility (AC1, 0.50-0.80) were obtained for the VI test. RT-qPCR reproducibility was low with kidney-brain tissue pairs (AC1, 0.09-0.46) and high with inter-test pairs of brain (AC1, 0.76-0.86) or kidney tissue (0.75-0.86). Tissue-specific differences in virus load affected test precision and informed final tissue selection. Repeatability (ccc, 0.94-0.97) and reproducibility (ccc, 0.91-0.97) estimates of agreement for paired continuous data from the RT-qPCR assays were similarly high with kidney tissue and lower with paired brain (ccc, 0.15-0.83) and kidney-brain tissues (ccc, 0.01-0.55). The high precision of Q1G and Q2N with kidney tissue suggests that the tests are performing similarly and are suitable candidates for assessment of their diagnostic accuracy.

Optimizing osteoporosis care in a rural primary health care center: Findings of a research study aimed to support seniors.

BACKGROUND: Osteoporosis is one of the most under-diagnosed and under-treated health conditions in Canada. This study questioned whether an invitation to self-refer for osteoporosis risk evaluation would improve the number of patients who were tested for bone mineral density (BMD) at a rural Primary Health Care Center (PHCC). PURPOSE: The purpose of this study is to improve osteoporosis care and decrease bone fracture risk in a population of patients 65 years of age and older. METHODOLOGY: A quasi-experimental research design was used to review screening rates of BMD testing and identified patients in this population who were at low, moderate, and high risk for developing osteoporosis. Screening rates at the PHCC were compared to screening rates at another rural PHCC in the province. CONCLUSION: The self-referral program for BMD testing and a nurse-led intervention resulted in an increased number of people who were BMD tested at the study PHCC compared with the control PHCC, and identified more male patients 65 years of age and older who were at risk for osteoporosis and bone fractures. Recommendations suggest future research in other provincial PHCCs that may encourage self-referral programs for BMD testing and improved osteoporosis care for patients 65 years of age and older.

Changes in colorectal cancer incidence in seven high-income countries: a population-based study.

BACKGROUND: The overall incidence of colorectal cancer is decreasing in many high-income countries, yet analyses in the USA and other high-income countries such as Australia, Canada, and Norway have suggested increasing incidences among adults younger than 50 years. We aimed to examine longitudinal and generational changes in the incidence of colon and rectal cancer in seven high-income countries. METHODS: We obtained data for the incidence of colon and rectal cancer from 21 population-based cancer registries in Australia, Canada, Denmark, Norway, New Zealand, Ireland, and the UK for the earliest available year until 2014. We used age-period-cohort modelling to assess trends in incidence by age group, period, and birth cohort. We stratified cases by tumour subsite according to the 10th edition of the International Classification of Diseases. Age-standardised incidences were calculated on the basis of the world standard population. FINDINGS: An overall decline or stabilisation in the incidence of colon and rectal cancer was noted in all studied countries. In the most recent 10-year period for which data were available, however, significant increases were noted in the incidence of colon cancer in people younger than 50 years in Denmark (by 3·1%), New Zealand (2·9%), Australia (2·9%), and the UK (1·8%). Significant increases in the incidence of rectal cancer were also noted in this age group in Canada (by 3·4%), Australia (2·6%), and the UK (1·4%). Contemporaneously, in people aged 50-74 years, the incidence of colon cancer decreased significantly in Australia (by 1·6%), Canada (1·9%), and New Zealand (3·4%) and of rectal cancer in Australia (2·4%), Canada (1·2%), and the UK (1·2%). Increases in the incidence of colorectal cancer in people younger than 50 years were mainly driven by increases in distal (left) tumours of the colon. In all countries, we noted non-linear cohort effects, which were more pronounced for rectal than for colon cancer. INTERPRETATION: We noted a substantial increase in the incidence of colorectal cancer in people younger than 50 years in some of the countries in this study. Future studies are needed to establish the root causes of this rising incidence to enable the development of potential preventive and early-detection strategies. FUNDING: Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, the Cancer Society of New Zealand, NHS England, Norwegian Cancer Society, Public Health Agency Northern Ireland, Scottish Government, Western Australia Department of Health, and Wales Cancer Network.

Seroprevalence of Lawsonia intracellularis in different swine populations in 3 provinces in Canada.

Porcine proliferative enteropathy caused by Lawsonia intracellularis is an important enteric disease in swine throughout the world. Information regarding the distribution of this pathogen in Canadian swine herds would be beneficial for the creation of control protocols. Pigs from Ontario, Quebec, and Alberta were tested by using an indirect immunofluorescence assay for antibodies to L. intracellularis. Pig seroprevalence was calculated as the proportion of pigs positive from total pigs tested in the targeted population. Seroprevalence (+/- standard error [s(x)]) in market hogs in Ontario from farrow-finish (FF) farms and finishing (FIN) farms were significantly different at 77% (s(x) = 7%) and 29% (s(x) = 15%), respectively. Seroprevalence for sows and gilts in FF and farrowing and nursery (FAR + NUR) farms in Ontario were 90% (s(x) = 3%) and 93% (s(x) = 6%), respectively. Seroprevalence in breeding females in Quebec from FF and FAR farms was 82% (s(x) = 5%) and 87% (s(x) = 3%), respectively. Seroprevalence (57%, s(x) = 8%) in finishing pigs in Alberta from FF farms was significantly different from that of multisite (MS) farms and FIN farms, 6% (s(x) = 6%) and 9% (s(x) = 5%), respectively. Lawsonia intracellularis appears to be widespread in Canada and the seroprevalence on FF farms is higher than that on FIN and MS farms, possibly due to the presence of breeding females or management differences.

Pneumococcal conjugate vaccination in Canadian infants and children younger than five years of age: Recommendations and expected benefits.

INTRODUCTION: Streptococcus pneumoniae infection may result in invasive pneumococcal disease (IPD), such as bacteremia, meningitis and bacteremic pneumonia, or in non-IPD, such as pneumonia, sinusitis and otitis media. In June 2001, a heptavalent pneumococcal conjugate vaccine (PCV7) (Prevnar, Wyeth Pharmaceuticals, Canada) was approved for use in children in Canada. The objective of the present paper is to review S pneumoniae-induced disease incidence and vaccine recommendations in Canadian infants and children younger than five years of age. Particular attention is given to the expected benefits of vaccination in Canada based on postmarketing data and economic modelling. METHODS: Searches were performed on PubMed and Web of Science databases and specific Canadian journals using the key words 'pneumococc*', 'vaccine', 'conjugate', 'infant' and 'Canadian'. RESULTS AND DISCUSSION: PCV7 appears to be safe and effective against IPD and non-IPD in children younger than five years of age and, more importantly, in children younger than two years of age (who are at highest risk for IPD). An examination of postmarketing data showed a reduction in incidence of pneumococcal disease in age groups that were vaccinated and in older age groups, indicating the likelihood of herd protection. Concurrently, there was a reduction in the occurrence of antimicrobial-resistant isolates. CONCLUSIONS: The results from the present review suggest that PCV7 is currently benefiting Canadian children and society by lowering S pneumoniae-associated disease. Additional gains from herd protection and further reductions in antimicrobial resistance will be achieved as more Canadian children younger than five years of age are routinely vaccinated with PCV7.

Risk factors for outbreaks of infectious salmon anemia in farmed Atlantic salmon, Salmo salar.

Infectious salmon anemia (ISA) is a viral disease occurring in farmed Atlantic salmon (Salmo salar) that is characterized by lethargy, anorexia, anemia and death. To control the disease in New Brunswick, Canada, 7.5 million fish from outbreak cages have been destroyed since 1997. Despite changes made by farmers, 2002 was the worst year ever for ISA losses in the region. We evaluated the associations between potential risk factors and ISA outbreaks in the Atlantic-salmon sites in New Brunswick. This was a multilevel study in which the site-level design was a retrospective cohort study while the cage-level design was a modified case-cohort study. The questionnaire was divided into site-level questions, cage-level questions and hatchery information. The important factors identified by this study can be categorized as environmental, farmer controlled or industry controlled according to the capacity to change or eliminate them. Environmental risk factors such as increasing the depth of the net (if nets were 3m, OR=3.34) are for the most part dictated by site location. Wild pollock (Pollachius virens) in the cage reflects the number of wild pollock that live in the site location. If there were >or=1000 pollock in the cage, the odds of disease in the cage increased 4.43-fold. Risk factors that are under farm control include increasing the number of times that the salmon are treated for sea lice (OR=3.31 if lice treatments are 99 g) and improving on the adaptation of smolts to seawater to reduce post-transfer mortalities (OR=4.52 if there was at least one cage with post-transfer mortalities >5%). The industry-controlled factors need to be addressed by the industry as a whole. Organizing boat travel to minimize the time and frequency of boats travelling to or by sites currently is being reviewed. This will be extremely important because the OR=9.43 if processing boats travel within 1 km of the site and the OR=4.03 if the site has dry feed delivered by the feed company. Because the hazard ratio increased stepwise from 1 if the nearest neighbor with ISA was >or=5 km up to 5.5 if the nearest site with ISA was within 0.5 km, increasing the distance between sites might be necessary for effective control.

Application of surveillance data in evaluation of diagnostic tests for infectious salmon anemia.

Infectious salmon anemia (ISA) is a viral disease in farmed Atlantic salmon Salmo salar, characterized by lethargy, anorexia, anemia and death. Test methods used for regulatory decisions to remove infected cages include the indirect fluorescent antibody test (IFAT), the reverse transcription-polymerase chain reaction test (RT-PCR), and virus isolation (VI). However, no thorough evaluation of these diagnostic tests has been carried out on field samples. The objective of this study was to evaluate the sensitivity and specificity of ISA diagnostic tests as individual tests and in combinations, using data collected by the provincial government surveillance program. Because a 'gold standard' reference test for ISA was not available, cage status was based on clinical disease records. A pool of fish from negative farms that had never had clinical ISA and a pool of fish from positive cages that were experiencing an outbreak of clinical ISA were obtained and assumed to be uninfected and infected respectively. A total of 1071 fish were used in this study. Depending on the test's cut-off value, the sensitivity and specificity for histopathology ranged from 30 to 73 and 72 to 99% respectively. IFAT had sensitivities and specificities in the range of 64 to 83 and 96 to 100% respectively. For the RT-PCR, sensitivity and specificity were 93 and 98% respectively. Test performances were also evaluated in series and in parallel combinations. Sensitivities are maximized when tests are evaluated in parallel, and ranged from 75 to 98%. Specificities are maximized when the tests are evaluated in series, and ranged from 99 to 100%. Current surveillance testing protocols should be reviewed to capitalize on this newly available information on test characteristics.

Performance characteristics of polymerase chain reaction and histological methods for the detection of Haplosporidium nelsoni in the eastern oyster (Crassostrea virginica).

Fitness for purpose and validation are increasingly becoming a benchmark in the development of test methods for the diagnosis of infectious diseases in aquatic animals. The design of the evaluation and the analysis of data are critical to demonstrate test method performance characteristics and fitness for purpose, as stated in the World Organization for Animal Health pathway for test validation. Three test methods for the detection of the oyster parasite Haplosporidium nelsoni were selected for the validation study described herein: histology, end-point polymerase chain reaction (PCR), and real-time PCR (qPCR). Preliminary work evaluated the analytical sensitivity and specificity of the PCR and qPCR assay in development. The following stage used test results on 100 oysters in 3 different laboratories to assess diagnostic sensitivity (DSe), diagnostic specificity (DSp), repeatability, and reproducibility. Repeatability and reproducibility were within 68-95%. The final part of the project evaluated DSe and DSp using test results on 400 oysters and results from the first 100 oysters tested. In the absence of a 100% gold standard test, latent class modeling methods were explored to characterize the tests (i.e., Bayesian analyses). For both PCR methods, DSe was >90%, and in the 60% range for histology, whereas DSp was >90% for all methods. Based on the results of this validation, a threshold cycle value of 30 for qPCR corresponds to the limit of sensitivity for histology where unreliable detection becomes more frequent, thus providing a threshold helpful in diagnostic settings where both histology and qPCR are used.

Human papillomavirus vaccine uptake in boys and girls in a school-based vaccine delivery program in Prince Edward Island, Canada.

BACKGROUND: In 2013, Prince Edward Island was the first province to introduce HPV vaccine universally to grade six boys in a school-based program. Because uptake rates in boys are unknown in this type of vaccination program, uptake of HPV vaccination in boys was measured and compared with uptake rates in girls and then analyzed with factors such as county, urban-rural location of the school, and school board to identify where the vaccine program could be improved. METHODS: HPV vaccination records from the provincial childhood immunization registry in PEI were merged with Department of Education data containing all grade six girls and boys in PEI. Vaccine uptakes between years and between sexes were compared using two sample tests of proportions. Logistic regression modeling which accounted for the hierarchical nature of the data was used to analyze associations between factors and uptake rates. RESULTS: Although uptake was high in boys and girls, a significantly greater proportion of girls (85%) received all three doses of the HPV vaccine compared to boys (79%; p=0.004). The odds of grade six girls being fully vaccinated for HPV were 1.5 times greater than of grade six boys, and the odds of students in the English Language School Board receiving all three doses were more than twice as great as the odds of French Language School Board students. CONCLUSIONS: HPV vaccination for boys in PEI has had a successful launch, almost reaching the Canadian Immunization Committee recommendations of >80% for the early years of a program. PEI has a highly organized Public Health Nursing program that is involved in all childhood and school-based vaccinations in PEI and in this context very high coverage rates were obtained. Areas to target for improving uptake include the boys and the students in the French Language School Board.

Static tank depuration and chronic short-term experimental contamination of Eastern oysters (Crassostrea virginica) with Giardia duodenalis cysts.

Cysts of the protozoan parasite Giardia have been detected in many bivalve shellfish species worldwide. The detection of zoonotic Giardia duodenalis assemblages A and B is of public health concern, yet there is limited data available demonstrating the bioaccumulation and elimination of Giardia cysts in bivalve shellfish. This study quantified G. duodenalis cysts that were filtered and retained by oysters (Crassostrea virginica) over a one week chronic exposure period, or 24 hour exposure followed by a 6 day depuration period, using static tank systems containing 10 L of 29 ppt water inoculated with 1000 or 10,000 cysts. Under chronic exposure, each oyster retained a mean of 13.4 and 87.4 cysts during the first 24h of exposure at low and high doses, respectively, and the cysts bioaccumulated at a rate of 1.2 and 6.8 cysts/oyster/day, respectively, for the remaining duration of the trials. In acute exposure trials, oysters retained 13.8 cysts or 78.9 cysts at low and high doses, respectively, during the initial 24 hour exposure and naturally depurated cysts at a rate of -0.92 cysts/oyster/day and -2.2 cysts/oyster/day, respectively, after transfer. Although most G. duodenalis cysts were eliminated within the first 24h via pseudofeces and feces, detection of some cysts in the fecal material on day 7 of acute exposure trials was indicative of cysts which passed through the digestive tract and released in feces. Only 48-53% of the initial tank inocula were recovered and may indicate that some cysts were selectively filtered by oysters but degraded through digestion.