In the absence of cancer registry data, is it sensible to assess incidence using hospital separation records?

BACKGROUND: Within the health literature, a major goal is to understand distribution of service utilisation by social location. Given equivalent access, differential incidence leads to an expectation of differential service utilisation. Cancer incidence is differentially distributed with respect to socioeconomic status. However, not all jurisdictions have incidence registries, and not all registries allow linkage with utilisation records. The British Columbia Linked Health Data resource allows such linkage. Consequently, we examine whether, in the absence of registry data, first hospitalisation can act as a proxy measure for incidence, and therefore as a measure of need for service. METHODS: Data are drawn from the British Columbia Linked Health Data resource, and represent 100% of Vancouver Island Health Authority cancer registry and hospital records, 1990–1999. Hospital separations (discharges) with principal diagnosis ICD-9 codes 140–208 are included, as are registry records with ICDO-2 codes C00-C97. Non-melanoma skin cancer (173/C44) is excluded. Lung, colorectal, female breast, and prostate cancers are examined separately. We compare registry and hospital annual counts and age-sex distributions, and whether the same individuals are represented in both datasets. Sensitivity, specificity and predictive values are calculated, as is the kappa statistic for agreement. The registry is designated the gold standard. RESULTS: For all cancers combined, first hospitalisation counts consistently overestimate registry incidence counts. From 1995–1999, there is no significant difference between registry and hospital counts for lung and colorectal cancer (p = 0.42 and p = 0.56, respectively). Age-sex distribution does not differ for colorectal cancer. Ten-year period sensitivity ranges from 73.0% for prostate cancer to 84.2% for colorectal cancer; ten-year positive predictive values range from 89.5% for female breast cancer to 79.35% for prostate cancer. Kappa values are consistently high. CONCLUSION: Claims and registry databases overlap with an appreciable proportion of the same individuals. First hospital separation may be considered a proxy for incidence with reference to colorectal cancer since 1995. However, to examine equity across cancer health services utilisation, it is optimal to have access to both hospital and registry files

Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

Abstract Introduction Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2). Methods To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. Results Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 × 10-4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 × 10-5, P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df-P = 0.007; rs1292011 2df-P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 × 10-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049). Conclusions The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers

Supplement 1. The Corrigan and the Nile Creek data sets and the S-PLUS functions for fitting the piecewise-regression models used in the paper.

<h2>File List</h2><p><i>All files at once</i></p> <blockquote> <p><a href="pw_regression.zip">pw_regression.zip</a></p> </blockquote> <p><i>Data files</i></p> <blockquote> <p><a href="corrigan_data.txt">corrigan_data.txt</a> - tab-delimited ASCII file of presence/absence data at the Corrigan site.</p> <p><a href="nile_creek_data.txt">nile_creek_data.txt</a> - tab-delimited ASCII file of presence/absence data at the Nile Creek site.</p> </blockquote> <p><i>S-PLUS files</i></p> <blockquote> <p><a href="pwreg_fns.txt">pwreg_fns.txt</a> - ASCII file of S-PLUS functions for fitting the piecewise regression models</p> <p><a href="fn_calls.txt">fn_calls.txt</a> - ASCII file of example function calls (will recreate most of the results in the paper)</p> </blockquote><h2>Description</h2>The files corrigan_data.txt and nile_creek_data.txt are tab-delimited ASCII files of the data used. Tree species are split into height categories (height >1.3 m, or <u><</u>1.3 m). In both files, columns 2–13 are from transect #1, columns 14–25 are from transect #2, and columns 26–37 are from transect #3. S-PLUS functions for fitting all piecewise-regression models in the paper (sharp, hyperbolic-tangent, bent-hyperbola, and bent-cable piecewise-regression models) are available in pwreg_fns.txt. The file also contains additional functions for deriving and plotting confidence intervals for an estimate of the breakpoint. Import these functions into a S-PLUS session using the internal S-PLUS function source. The functions are known to work in S-PLUS version 4.5 and 6.1 for Windows. The results for the case study can then be recreated using the commands listed in fn_calls.txt. As written, the function calls assume that the first PCA axis for the Corrigan data has been extracted and called corpapca.df, that the first PCA axis for the Nile Creek data has been extracted and called nilpapca.df, and that a vector of distances from edge has been created and called distance

Supplement—Validation of a multivariate clinical prediction model for the diagnosis of mild stroke/TIA in physician first-contact patient settings

Supplementary Table S1 for paper: Validation of a multivariate clinical prediction model for the diagnosis of mild stroke/TIA in physician first-contact patient settings

Reducing time-to-unit among patients referred to an outpatient stroke assessment unit with a novel triage process: a prospective cohort study

Background: To evaluate the performance of a novel triage system for Transient Ischemic Attack (TIA) units built upon an existent clinical prediction rule (CPR) to reduce time to unit arrival, relative to the time of symptom onset, for true TIA and minor stroke patients. Differentiating between true and false TIA/minor stroke cases (mimics) is necessary for effective triage as medical intervention for true TIA/minor stroke is time-sensitive and TIA unit spots are a finite resource. Methods: Prospective cohort study design utilizing patient referral data and TIA unit arrival times from a regional fast-track TIA unit on Vancouver Island, Canada, accepting referrals from emergency departments (ED) and general practice (GP). Historical referral cohort (N = 2942) from May 2013–Oct 2014 was triaged using the ABCD2 score; prospective referral cohort (N = 2929) from Nov 2014–Apr 2016 was triaged using the novel system. A retrospective survival curve analysis, censored at 28 days to unit arrival, was used to compare days to unit arrival from event date between cohort patients matched by low (0–3), moderate (4–5) and high (6–7) ABCD2 scores. Results: Survival curve analysis indicated that using the novel triage system, prospectively referred TIA/minor stroke patients with low and moderate ABCD2 scores arrived at the unit 2 and 1 day earlier than matched historical patients, respectively. Conclusions: The novel triage process is associated with a reduction in time to unit arrival from symptom onset for referred true TIA/minor stroke patients with low and moderate ABCD2 scores.Science, Faculty ofOther UBCNon UBCStatistics, Department ofReviewedFacult

Performance of a RT-PCR Assay in Comparison to FISH and Immunohistochemistry for the Detection of ALK in Non-Small Cell Lung Cancer

Patients with lung cancers harboring an activating anaplastic lymphoma kinase (ALK) rearrangement respond favorably to ALK inhibitor therapy. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are validated and widely used screening tests for ALK rearrangements but both methods have limitations. The ALK RGQ RT-PCR Kit (RT-PCR) is a single tube quantitative real-time PCR assay for high throughput and automated interpretation of ALK expression. In this study, we performed a direct comparison of formalin-fixed paraffin-embedded (FFPE) lung cancer specimens using all three ALK detection methods. The RT-PCR test (diagnostic cut-off ΔCt of ≤8) was shown to be highly sensitive (100%) when compared to FISH and IHC. Sequencing of RNA detected full-length ALK transcripts or EML4-ALK and KIF5B-ALK fusion variants in discordant cases in which ALK expression was detected by the ALK RT-PCR test but negative by FISH and IHC. The overall specificity of the RT-PCR test for the detection of ALK in cases without full-length ALK expression was 94% in comparison to FISH and sequencing. These data support the ALK RT-PCR test as a highly efficient and reliable diagnostic screening approach to identify patients with non-small cell lung cancer whose tumors are driven by oncogenic ALK.Medicine, Faculty ofMedical Oncology, Division ofMedicine, Department ofPathology and Laboratory Medicine, Department ofReviewedFacult

Establishing the Signal above the Noise: Accounting for an Environmental Background in the Detection and Quantification of Salmonid Environmental DNA

A current challenge for environmental DNA (eDNA) applications is how to account for an environmental (or false-positive) background in surveys. We performed two controlled experiments in the Goldstream Hatchery in British Columbia using a validated coho salmon (Oncorhynchus kisutch) eDNA assay (eONKI4). In the density experiment at high copy number, eDNA in 2 L water samples was measured from four 10 kL tanks containing 1 to 65 juvenile coho salmon. At these densities, we obtained a strong positive 1:1 relationship between predicted copy number/L and coho salmon biomass (g/L). The dilution experiment simulated a situation where fish leave a pool environment, and water from upstream continues to flow through at rates of 141&ndash;159 L/min. Here, three coho salmon were placed in four 10 kL tanks, removed after nine days, and the amount of remaining eDNA was measured at times coinciding with dilutions of 20, 40, 80, 160, and 1000 kL. The dilution experiment demonstrates a novel method using Binomial&ndash;Poisson distributions to detect target species eDNA at low copy number in the presence of an environmental background. This includes determination of the limit of blank with background (LOB-B) with a controlled false positive rate, and limit of detection with background (LOD-B) with a controlled false negative rate, which provides a statistically robust &ldquo;Detect&rdquo; or &ldquo;No Detect&rdquo; assessment for eDNA surveys

Establishing the Signal above the Noise: Accounting for an Environmental Background in the Detection and Quantification of Salmonid Environmental DNA

A current challenge for environmental DNA (eDNA) applications is how to account for an environmental (or false-positive) background in surveys. We performed two controlled experiments in the Goldstream Hatchery in British Columbia using a validated coho salmon (Oncorhynchus kisutch) eDNA assay (eONKI4). In the density experiment at high copy number, eDNA in 2 L water samples was measured from four 10 kL tanks containing 1 to 65 juvenile coho salmon. At these densities, we obtained a strong positive 1:1 relationship between predicted copy number/L and coho salmon biomass (g/L). The dilution experiment simulated a situation where fish leave a pool environment, and water from upstream continues to flow through at rates of 141–159 L/min. Here, three coho salmon were placed in four 10 kL tanks, removed after nine days, and the amount of remaining eDNA was measured at times coinciding with dilutions of 20, 40, 80, 160, and 1000 kL. The dilution experiment demonstrates a novel method using Binomial–Poisson distributions to detect target species eDNA at low copy number in the presence of an environmental background. This includes determination of the limit of blank with background (LOB-B) with a controlled false positive rate, and limit of detection with background (LOD-B) with a controlled false negative rate, which provides a statistically robust “Detect” or “No Detect” assessment for eDNA surveys

Systolic blood pressure as a predictor of transient ischemic attack/minor stroke in emergency department patients under age 80: a prospective cohort study

Abstract Background Elevated blood pressure (BP) at emergency department (ED) presentation and advancing age have been associated with risk of ischemic stroke; however, the relationship between BP, age, and transient ischemic attack/minor stroke (TIA/MS) is not clear. Methods A multi-site, prospective, observational study of 1084 ED patients screened for suspected TIA/MS (symptom onset < 24 h, NIHSS< 4) between December 2013 and April 2016. Systolic and diastolic BP measurements (SBP, DBP) were taken at ED presentation. Final diagnosis was consensus adjudication by stroke neurologists; patients were diagnosed as either TIA/MS or stroke-mimic (non-cerebrovascular conditions). Conditional inference trees were used to define age cut-points for predicting binary diagnosis (TIA/MS or stroke-mimic). Logistic regression models were used to estimate the effect of BP, age, sex, and the age-BP interaction on predicting TIA/MS diagnosis. Results Over a 28-month period, 768 (71%) patients were diagnosed with TIA/MS: these patients were older (mean 71.6 years) and more likely to be male (58%) than stroke-mimics (61.4 years, 41%; each p < 0.001). TIA/MS patients had higher SBP than stroke-mimics (p < 0.001). DBP did not differ between the two groups (p = 0.191). SBP was predictive of TIA/MS diagnosis in younger patients, after accounting for age and sex; an increase of 10 mmHg systolic increased the odds of TIA/MS 18% (odds ratio [OR] 1.18, 95% CI 1.00–1.39) in patients < 60 years, and 23% (OR 1.23, 95% CI 11.12–1.35) in those 60–79 years, while not affecting the odds of TIA/MS in patients ≥80 years (OR 0.99, 95% CI 0.89–1.07). Conclusions Raised SBP in patients younger than 80 with suspected TIA/MS may be a useful clinical indicator upon initial presentation to help increase clinicians’ suspicion of TIA/MS. Trial registration ClinicalTrials.gov NCT03050099 (10-Feb-2017) and NCT03070067 (3-Mar-2017). Retrospectively registered