Serum 25-hydroxyvitamin D and risk of cancer in a large community population under investigation for cardiovascular disease: a retrospective cohort study.

OBJECTIVES: It remains unclear whether vitamin D status is related to cancer risk. We examined this relationship using laboratory, administrative and survey data. DESIGN: Retrospective cohort study. SETTING: All care settings within Calgary, Alberta, Canada and surrounding rural communities. PARTICIPANTS: Patients tested for serum 25-hydroxyvitamin D from 2009 to 2013 without a past cancer diagnosis but with an ECG and body mass index ±3 months from testing were included. Age, sex, mean hours of daylight during month of testing were linked to census dissemination area-level indicators of socioeconomic status measured in 2011. PRIMARY AND SECONDARY OUTCOME MEASURES: Hospital discharge diagnoses for any cancer, major cancer (colorectal, breast, lung, prostate, skin) and other cancers >3 months from testing from 2009 to 2016. Cox proportional hazard models were used to examine associations with incident cancer after adjusting for potential confounders. Interactions were tested using multiplicative terms. RESULTS: Among 72 171 patients, there were 3439 cancer diagnoses over a median of 5.9 years. After adjustment, increasing quartile of serum 25-OH vitamin D was significantly associated with an increased risk of any cancer and major cancer, however this was completely driven by an increased risk of skin cancer (Q4 vs Q1: HR=2.56, 95% CI 1.70 to 3.86, p for linear trend <0.01). This association was strengthened among individuals residing in communities with higher proportions of non-citizens, recent immigrants, visible (non-white) minorities and those not speaking an official Canadian language (English or French) at home. CONCLUSIONS: Higher vitamin D status was associated with a greater risk of skin cancer in a large community population under investigation for cardiovascular disease. This association was likely due to sun exposure and may be modified by community variation in vitamin D supplementation.

Cervical Screening Practices and Outcomes for Young Women in Response to Changed Guidelines in Calgary, Canada, 2007-2016.

OBJECTIVE: The aim of the study was to describe temporal trends in screening and outcomes for women, after changes in guidelines in Alberta, Canada, that raised starting age to 21 years, then to 25 years of age, and reduced frequency to 3 yearly. MATERIALS AND METHODS: Calgary Laboratory Information System data were used to examine screening rates, follow-up procedures, and cancer among women 10-29 years from 2007 to 2016 in the whole population of Calgary. Interrupted time-series analyses were used to assess changes in screening and subsequent diagnostic procedures over the 10-year period. RESULTS: Annual screening rates dropped by approximately 10% at all ages older than 15 years after the 2009 Alberta cervical cancer screening guidelines, followed by a steady decrease. Further change continued subsequent to minimal apparent effect of the 2013 Canadian Task Force on Preventive Health Care guidelines. The rates of abnormal test results decreased in concert with decreased screening. No increases in cervical intraepithelial neoplasia 1, cervical intraepithelial neoplasia 2/3, or invasive cervical cancer rates were observed after reduced testing. CONCLUSIONS: The largest decrease in screening and follow-up procedures occurred in the period immediately after implementation of 2009 Alberta screening guidelines. The number of consequent procedures also decreased in proportion to decreased screening, but there was no increase in cancer rates. Starting screening at the age of 25 years and reducing intervals seem to be safe.

Potentially Inappropriate Prescribing and Potential Prescribing Omissions in 82,935 Older Hospitalised Adults: Association with Hospital Readmission and Mortality Within Six Months.

Polypharmacy with "potentially inappropriate medications" (PIMs) and "potential prescribing omissions" (PPOs) are frequent among those 65 and older. We assessed PIMs and PPOs in a retrospective study of 82,935 patients ≥ 65 during their first admission in the period March 2013 through February 2018 to the four acute-care Calgary hospitals. We used the American Geriatric Society (AGS) and STOPP/START criteria to assess PIMs and PPOs. We computed odds ratios (ORs) for key outcomes of concern to patients, their families, and physicians, namely readmission and/or mortality within six months of discharge, and controlled for age, sex, numbers of medications, PIMs, and PPOs. For readmission, the adjusted OR for number of medications was 1.09 (1.09-1.09), for AGS PIMs 1.14 (1.13-1.14), for STOPP PIMs 1.15 (1.14-1.15), for START PPOs 1.04 (1.02-1.06), and for START PPOs correctly prescribed 1.16 (1.14-1.17). For mortality within 6 months of discharge, the adjusted OR for the number of medications was 1.02 (1.01-1.02), for STOPP PIMs 1.07 (1.06-1.08), for AGS PIMs 1.11 (1.10-1.12), for START PPOs 1.31 (1.27-1.34), and for START PPOs correctly prescribed 0.97 (0.94-0.99). Algorithm rule mining identified an 8.772 higher likelihood of mortality with the combination of STOPP medications of duplicate drugs from the same class, neuroleptics, and strong opioids compared to a random relationship, and a 2.358 higher likelihood of readmission for this same set of medications. Detailed discussions between patients, physicians, and pharmacists are needed to improve these outcomes.

Is the Utilization of Helicobacter pylori Stool Antigen Tests Appropriate in an Urban Canadian Population?

OBJECTIVES: Helicobacter pylori stool antigen test (HpSAT) appropriateness was investigated by assessing its testing and positivity rates in Calgary, Canada. METHODS: The laboratory information system was accessed for all patients who received an HpSAT in 2018. Testing volume, test results, age, and sex of patients were collected. Sociodemographic risk factors and geospatial analysis were performed by matching laboratory data to the 2016 census data. Testing appropriateness was defined as a concordance between testing and positivity rates for each sociodemographic variable. RESULTS: In 2018, 25,518 H pylori stool antigen tests were performed in Calgary, with an overall positivity rate of 14.7%. Geospatial mapping demonstrated significant distribution variations of testing and positivity rates of HpSAT in the city. Certain sociodemographic groups studied (eg, recent immigrants) appeared to be appropriately tested (testing rate relative risk [RR] = 2.26, positivity rate RR = 4.32; P < .0001), while other groups (eg, male) may have been undertested (testing rate RR = 0.85, positivity rate RR = 1.14; P < .0001). CONCLUSIONS: Determining concordance of testing and positivity rate of a laboratory test can be used for assessing testing appropriateness for other diseases in other jurisdictions. This study demonstrated some at-risk patients may be missed for H pylori testing.

Incidence of myeloproliferative neoplasms in Calgary, Alberta, Canada.

OBJECTIVE: The incidence of the combined myeloproliferative neoplasms (MPNs) was determined for a major Canadian city. Retrospective cases of MPN diagnoses (essential thrombocythemia, polycythemia vera, and primary myelofibrosis) between 2011 to 2015 were retrieved from the Southern Alberta Cancer Cytogenetics Laboratory's database at Alberta Public Laboratories. RESULTS: An incidence rate of 2.05 cases per 100,000 person-years (95% CI 1.73-2.41) was determined, giving an age-standardized Canadian incidence of 2.71 cases per 100,000 person years (95% CI 2.63-2.78). MPN diagnoses occurred at a wide age range of 8-93 (median 66) and an age-dependent increase in incidence. Incidence rates for the MPNs are first reported here for a Canadian population.

Utility of Multistep Protocols in the Analysis of Sentinel Lymph Nodes in Cutaneous Melanoma: An Assessment of 194 Cases.

CONTEXT.­: Currently, no universal protocol exists for the assessment of sentinel lymph nodes (SLNs) in cutaneous melanoma. Many institutions use a multistep approach with multiple hematoxylin-eosin (H&E) and immunohistochemical stains. However, this can be a costly and time- and resource-consuming task. OBJECTIVE.­: To assess the utility for multistep protocols in the analysis of melanoma SLNs by specifically evaluating the Calgary Laboratory Services (CLS) protocol (which consists of 3 H&E slides and 1 S100 protein, 1 HMB-45, and 1 Melan-A slide per melanoma SLN block) and to develop a more streamlined protocol. DESIGN.­: Histologic slides from SLN resections from 194 patients with diagnosed cutaneous melanoma were submitted to the CLS dermatopathology group. Tissue blocks were processed according to the CLS SLN protocol. The slides were re-reviewed to determine whether or not metastatic melanoma was identified microscopically at each step of the protocol. Using SPSS software, a decision tree was then created to determine which step most accurately reflected the true diagnosis. RESULTS.­: We found with Melan-A immunostain that 337 of 337 negative SLNs (100%) were correctly diagnosed as negative and 55 of 56 positive nodes (98.2%) were correctly diagnosed as positive. With the addition of an H&E level, 393 of 393 SLNs (100%) were accurately diagnosed. CONCLUSIONS.­: We recommend routine melanoma SLN evaluation protocols be limited to 2 slides: 1 H&E stain and 1 Melan-A stain. This protocol is both time- and cost-efficient and yields high diagnostic accuracy.

Red cell distribution width associations with clinical outcomes: A population-based cohort study.

IMPORTANCE: Higher levels of red cell distribution width (RDW) are associated with adverse outcomes, especially in selected cohorts with or at risk for chronic disease. Whether higher RDW or the related parameter standard deviation of the red blood cell distribution (SD-RBC) can predict a broader range of outcomes in the general population is unknown. OBJECTIVE: To evaluate the association of RDW and SD-RBC with the risk of adverse outcomes in people from the general population. DESIGN: Population-based retrospective cohort study. SETTING: Health care system in a Canadian province (Alberta). PARTICIPANTS: All 3,156,863 adults living in Alberta, Canada with at least one measure of RDW and SD-RBC between 2003 and 2016. Data were analyzed in September 2018. EXPOSURE: RDW and SD-RBC, classified into percentiles (<1, 1-5, 5-25, 25-75, 75-95, 95-99, >99). MAIN OUTCOMES: All-cause death, first myocardial infarction, first stroke or transient ischemic attack, placement into long-term care (LTC), progression to renal replacement therapy (initiation of chronic dialysis or pre-emptive kidney transplantation), incident solid malignancy, and first hospitalization during follow-up. RESULTS: Over median follow-up of 6.8 years, 209,991 of 3,156,863 participants (6.7%) died. The risk of death increased with increasing RDW percentile. After adjustment, and compared to RDW in the 25th to 75th percentiles, the risk of death was lower for participants in the <25th percentiles but higher for participants in the 75th-95th percentiles (HR 1.42, 95% CI 1.40,1.43), the 95th-99th percentiles (HR 1.86, 95% CI 1.83,1.89) and the >99th percentile (HR 2.18, 95% CI 2.12,2.23). Similar results were observed for MI, stroke/TIA, incident cancer, hospitalization and LTC placement, but no association was found between RDW and ESRD. Findings were generally similar for SD-RBC, except that all associations tended to be stronger than for RDW, and both lower and higher values of SD-RBC were independently associated with ESRD. CONCLUSION AND RELEVANCE: RDW and SD-RBC may be useful as prognostic markers for people in the general population, especially for outcomes related to chronic illness. SD-RBC may be superior to RDW.

Utility of Ber-EP4 and MOC-31 in Basaloid Skin Tumor Detection.

Ber-EP4 has been the traditional immunostain used for the detection of basaloid skin tumors. Recently, MOC-31 has shown be superior to Ber-EP4 in the detection of basosquamous basal cell carcinoma (BCC) and many centers are now using both Ber-EP4 and MOC-31 antibodies together to detect these lesions. The objective of this study was to compare the utility of using both Ber-EP4 and MOC-31 immunostains in the detection of basaloid skin tumors and to better characterize the previously unknown staining properties of MOC-31 in cutaneous lesions. To do this, 76 basaloid skin tumors stained with both Ber-EP4 and MOC-31 were obtained. Diagnoses included basosquamous BCC, Merkel cell carcinoma, adenoid cystic carcinoma, microcystic adnexal carcinoma, sebaceous carcinoma, trichoepithelioma, trichoblastoma, sebaceous adenoma, sebaceoma, and follicular induction overlying dermatofibroma. The distribution and intensity of Ber-EP4 and MOC-31 staining in these lesions was scored. These scores were analyzed using a truth table, χ test, and Pearson correlation tests. The overall mean and SD of the scores were also obtained. Overall, we found Ber-EP4 and MOC-31 to be statistically equivalent immunostains for the diagnosis of basaloid skin tumors. We recommend the use of only one of these antibodies and favor MOC-31 for the detection of basaloid skin tumors. We also describe MOC-31 staining properties in different cutaneous lesions.

Incidence of chronic myeloid leukemia in Calgary, Alberta, Canada.

OBJECTIVE: The epidemiology of chronic myeloid leukemia is shifting due to the aging global population and the recent discovery and availability of targeted treatment options. This study provides recent data regarding the incidence of CML in Calgary, a major Canadian city. Data from patients diagnosed with CML by bone marrow sample analysis from 2011 to 2015 were collected from the database of the sole centralized cytogenetics facility in service of Calgary and its surrounding area. RESULTS: With an average of 10.2 newly diagnosed cases per year in Calgary from 2011 to 2015, the incidence rate was calculated to be 0.75 cases per 100,000 person-years (95% CI 0.57-0.99). With age standardization, the incidence was 0.87 cases per 100,000 person-years (95% CI 0.82-0.91) for the Canadian population, which was low compared to other developed Western nations. The highest incidence rates were observed in the older patient categories, however there was a broad age distribution for incident cases and the median age at diagnosis was 48. There was a general male bias for CML most pronounced at the younger ages. Our description of CML incidence will help to inform healthcare planners amidst the dramatically altered treatment of this hematological neoplasm.

Sociodemographic associations with abnormal estimated glomerular filtration rate (eGFR) in a large Canadian city: a cross-sectional observation study.

BACKGROUND: Chronic kidney disease (CKD) is often asymptomatic in its early stages but is indicated and is diagnosed with an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2. Certain sociodemographic groups are known to be at risk for CKD, but it is unclear if there are strong associations between these at risk groups with abnormal eGFR test results in Canada. Using only secondary laboratory and Census data, geospatial variation and sociodemographic associations with abnormal eGFR result rate were investigated in Calgary, Alberta. METHODS: Secondary laboratory data from all adult community patients who received an eGFR test result were collected from Calgary Laboratory Service's Laboratory Information System, which is the sole supplier of laboratory services for the large metropolitan city. Group-level sociodemographic variables were inferred by combining laboratory data with the 2011 Canadian Census data. Poisson regression and relative risk (RR) were used to calculate associations between sociodemographic variables with abnormal eGFR. Geographical distribution of abnormal eGFR result rates were analyzed by geospatial analysis using ArcGIS. RESULTS: Of the 346,663 adult community patients who received an eGFR test result, 28,091 were abnormal (8.1%; eGFR < 60 ml/min/1.73m2). Geospatial analysis revealed distinct geographical variation in abnormal eGFR result rates in Calgary. Women (RR = 1.11, P < 0.0001), and the elderly (age ≥ 70 years; P < 0.0001) were significantly associated with an increased risk for CKD, while visible minority Chinese (RR = 0.73, P = 0.0011), South Asians (RR = 0.67, P < 0.0001) and those with a high median household income (RR = 0.88, P < 0.0001) had a significantly reduced risk for CKD. CONCLUSIONS: Presented here are significant sociodemographic risk associations, and geospatial clustering of abnormal eGFR result rates in a large metropolitan Canadian city. Using solely publically available secondary laboratory and Census data, the results from this study aligns with known sociodemographic risk factors for CKD, as certain sociodemographic variables were at a higher risk for having an abnormal eGFR test result, while others were protective in this analysis.

Incidence of acute lymphocytic leukemia in Calgary, Alberta, Canada: a retrospective cohort study.

OBJECTIVE: Acute lymphocytic leukemia (ALL) is a rare malignant neoplasm that develops from abnormal lymphoid stem cells. ALL incidence is highest among children and declines towards adolescence. There is limited data on the epidemiology of ALL, especially in Canada. This retrospective cohort study used patient data from the Calgary Laboratory Services Cancer Cytogenetics Laboratory to report the incidence rate of ALL in Calgary, Alberta, Canada. New cases of ALL were identified for the 5-year period of January 1, 2011 until December 31, 2015. Reported incidence rates were categorized by sex and age groups, and age-standardized to the Canadian population. RESULTS: There were an average of 11.4 new cases of ALL diagnosed per year between 2011 and 2015. The total incidence rate per 100,000 person-years was 0.84. Incidence rates peaked in children aged 0-4 with 7.55 and 3.32 cases per 100,000 person-years for males and females, respectively. The median age of diagnosis was 8 years. Incidence rates were generally lowest for adults aged 20 and over. The ratio of males to females diagnosed with ALL was 1.59. Overall, the recent incidence of ALL in Calgary is comparatively low with a preference for males and children below 5 years of age.

Benjamin Terry and his rapid razor section method for intraoperative diagnosis.

Benjamin Taylor Terry (1876-1955), a little-known pathologist, played a critical role in the popularization of intraoperative diagnostic techniques in the 1920s and 1930s. He developed both a stain and his own rapid razor section method. Intraoperative diagnostic techniques were ultimately responsible for the transition of the practice of pathology and laboratory medicine from private commercial laboratories to a hospital-based practice, forever changing the history of pathology and surgery in North America. Although the intraoperative diagnostic technique he personally developed was reportedly better, faster and more economical than frozen sections, the latter ultimately won the battle for intraoperative diagnostic supremacy.

Incidence of Myelodysplastic Syndromes in a Major Canadian Metropolitan Area.

BACKGROUND: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders that can progress to acute myeloid leukemia. In many regions of the world, the epidemiology of MDS is poorly described. This study determines the crude incidence of MDS in Calgary, Alberta, Canada, with new cases diagnosed using the revised 2008 WHO criteria. METHODS: For the study period of January 1, 2011 to December 31, 2015, incident cases of MDS were identified from a centralized database maintained by Calgary Laboratory Services' Cancer Cytogenetics Laboratory, which receives and analyzes patient bone marrow samples from southern Alberta. RESULTS: The Calgary metropolitan area had a total incidence rate of 2.60 MDS cases per 100000 person years, corresponding to an age-standardized incidence of 3.69 for Canada. The male-to-female sex ratio was 1.35, and the median age at diagnosis was 75 years. With these results, 1295 new annual cases of MDS were predicted in Canada. CONCLUSIONS: The reported incidence rate, sex, and age distribution were consistent with data around the world including several developing nations. This is the first study to provide information regarding the epidemiology of MDS within Canada.

Influence of diurnal variation and fasting on serum iron concentrations in a community-based population.

OBJECTIVES: Serum iron is an important clinical test to help identify cases of iron deficiency or overload. Fluctuations caused by diurnal variation and diet are thought to influence test results, which may affect clinical patient management. We examined the impact of these preanalytical factors on iron concentrations in a large community-based cohort. DESIGN AND METHODS: Serum iron concentration, blood collection time, fasting duration, patient age and sex were obtained for community-based clinical testing from the Laboratory Information Service at Calgary Laboratory Services for the period of January 2011 to December 2015. RESULTS: A total of 276,307 individual test results were obtained. Iron levels were relatively high over a long period from 8:00 to 15:00. Mean concentrations were highest at blood collection times of 11:00 for adult men and 12:00 for adult women and children, however iron levels peaked as late as 15:00 in teenagers. With regard to fasting, iron levels required approximately 5h post-prandial time to return to a baseline, except for children and teenage females where no significant variation was seen until after 11h fasting. After 10h fasting, iron concentrations in all patient groups gradually increased to higher levels compared to earlier fasting times. CONCLUSIONS: Serum iron concentrations remain reasonably stable during most daytime hours for testing purposes. In adults, blood collection after 5 to 9h fasting provides a representative estimate of a patient's iron levels. For patients who have fasted overnight, i.e. ≥12h fasting, clinicians should be aware that iron concentrations may be elevated beyond otherwise usual levels.

The incidence of acute myeloid leukemia in Calgary, Alberta, Canada: a retrospective cohort study.

BACKGROUND: The incidence rate of acute myeloid leukemia (AML) was determined in the Calgary Metropolitan Area, a major Canadian city. METHODS: Data from all patients diagnosed with AML between January 1, 2011 and December 31, 2015 were retrieved from a single, centralized cancer cytogenetics laboratory for bone marrow samples, the sole diagnostic facility of its kind in Southern Alberta. RESULTS: The calculated incidence rate was 2.79 cases per 100,000 person-years with a median age of 60, slightly lower than previously published data. The age-standardized incidence rate for Canada was 3.46 cases per 100,000 person-years. The higher value is reflective of Calgary's younger population compared to the rest of Canada. Higher male incidence and greatest incidence occurring at approximately the age of 85 is similar to data from other developed countries. The lower incidence rates and median age of diagnosis, in comparison with that of other high-income nations, may be due to differences in the proportion of aging citizens in the population. CONCLUSION: This is the first published incidence rate of acute myeloid leukemia (AML) in Canada across all age groups.

Defining Benchmarks for Adenoma Detection Rate and Adenomas Per Colonoscopy in Patients Undergoing Colonoscopy Due to a Positive Fecal Immunochemical Test.

OBJECTIVES: Although there is an accepted benchmark for adenoma detection rate (ADR) in average risk screening colonoscopy, a benchmark for ADR or the associated quality indicator, adenomas per colonoscopy (APC), for colonoscopies performed for a positive fecal immunochemical test (FIT+) has not been established. The purpose of this study was to propose methods for establishing a benchmark ADR and APC for FIT+ patients. METHODS: In this historical cohort study, we included 15,329 patients aged 50-74 years who underwent a colonoscopy at Alberta Health Services' Colon Cancer Screening Centre, Calgary, Canada, from 1 January 2014 to 30 June 2015 for either investigation of a positive FIT or average risk screening. Using meta-regression, we estimated for FIT+ patients the ADR and APC that corresponded to (Method #1: minimally acceptable) an ADR of 25% in average risk individuals, (Method #2: standard of care) the average ADR or APC in all FIT+ patients, and (Method #3: aspirational) the average FIT+ ADR or APC in colonoscopies performed by endoscopists with an ADR of ≥35% in average risk patients. RESULTS: At least one adenoma was detected in 30% of average risk patients and 58% of FIT+ patients. The calculated benchmark FIT+ ADRs for the three methods were 55, 60, and 65%, respectively. The calculated benchmarks for FIT+ APC were 1.2, 1.4, and 1.7, respectively. To account for expected random variation in individual endoscopists' ADR or APC, we propose using the upper bound of the 95% confidence interval of an endoscopist's ADR or APC to determine if they fall below a given benchmark. CONCLUSIONS: We have proposed methods of defining benchmarks for ADR and APC in FIT+ patients that go beyond the current "minimally acceptable" threshold currently recommended in average risk patients. These new thresholds represent results obtained by all peers and by a group of expert adenoma detectors defined in an independent patient cohort (average risk). Because the true adenoma burden in FIT+ patients could vary based on factors such as the threshold used to define a positive FIT, screening programs or endoscopy units may need to calculate their own benchmarks using local data.

A re-examination of the role of the acute phase protein response in innate cancer defence.

Anti-cancer host defense mechanisms are traditionally considered to consist of tumor suppressor genes and immune surveillance by cells of the innate and adaptive immune systems. However, there is mounting evidence that components of the acute phase protein response (APPR), and, in particular, certain cationic host defense peptides (HDPs), also contribute to anti-cancer host defense. In a number of in vitro studies, certain HDPs have been shown to be cytotoxic to tumor cells either directly through cancer cell membrane destabilization and lysis or through the initiation of apoptosis in the cancer cell. In addition, many cancer cells elaborate the pro-inflammatory cytokine interleukin-6, which in turn produces an APPR that involves the release of HDPs. It is therefore possible that the release of pro-inflammatory cytokines by cancer cells initiates a poorly understood anti-tumor response by the host that involves HDP induction. We hypothesize that the APPR may form an important anti-cancer host defense response. This may be an important consideration in light of cancer treatments designed to decrease systemic inflammation. Blunting of the anti-cancer effect of the APPR may also contribute to the increased cancer rates seen in chronic immunosuppressive states.

An Immunohistochemical Algorithm for Ovarian Carcinoma Typing.

There are 5 major histotypes of ovarian carcinomas. Diagnostic typing criteria have evolved over time, and past cohorts may be misclassified by current standards. Our objective was to reclassify the recently assembled Canadian Ovarian Experimental Unified Resource and the Alberta Ovarian Tumor Type cohorts using immunohistochemical (IHC) biomarkers and to develop an IHC algorithm for ovarian carcinoma histotyping. A total of 1626 ovarian carcinoma samples from the Canadian Ovarian Experimental Unified Resource and the Alberta Ovarian Tumor Type were subjected to a reclassification by comparing the original with the predicted histotype. Histotype prediction was derived from a nominal logistic regression modeling using a previously reclassified cohort (N=784) with the binary input of 8 IHC markers. Cases with discordant original or predicted histotypes were subjected to arbitration. After reclassification, 1762 cases from all cohorts were subjected to prediction models (χ Automatic Interaction Detection, recursive partitioning, and nominal logistic regression) with a variable IHC marker input. The histologic type was confirmed in 1521/1626 (93.5%) cases of the Canadian Ovarian Experimental Unified Resource and the Alberta Ovarian Tumor Type cohorts. The highest misclassification occurred in the endometrioid type, where most of the changes involved reclassification from endometrioid to high-grade serous carcinoma, which was additionally supported by mutational data and outcome. Using the reclassified histotype as the endpoint, a 4-marker prediction model correctly classified 88%, a 6-marker 91%, and an 8-marker 93% of the 1762 cases. This study provides statistically validated, inexpensive IHC algorithms, which have versatile applications in research, clinical practice, and clinical trials.

Interventions to Educate Family Physicians to Change Test Ordering: Systematic Review of Randomized Controlled Trials.

The purpose is to systematically review randomised controlled trials (RCTs) to change family physicians' laboratory test-ordering. We searched 15 electronic databases (no language/date limitations). We identified 29 RCTs (4,111 physicians, 175,563 patients). Six studies specifically focused on reducing unnecessary tests, 23 on increasing screening tests. Using Cochrane methodology 48.5% of studies were low risk-of-bias for randomisation, 7% concealment of randomisation, 17% blinding of participants/personnel, 21% blinding outcome assessors, 27.5% attrition, 93% selective reporting. Only six studies were low risk for both randomisation and attrition. Twelve studies performed a power computation, three an intention-to-treat analysis and 13 statistically controlled clustering. Unweighted averages were computed to compare intervention/control groups for tests assessed by >5 studies. The results were that fourteen studies assessed lipids (average 10% more tests than control), 14 diabetes (average 8% > control), 5 cervical smears, 2 INR, one each thyroid, fecal occult-blood, cotinine, throat-swabs, testing after prescribing, and urine-cultures. Six studies aimed to decrease test groups (average decrease 18%), and two to increase test groups. Intervention strategies: one study used education (no change): two feedback (one 5% increase, one 27% desired decrease); eight education + feedback (average increase in desired direction >control 4.9%), ten system change (average increase 14.9%), one system change + feedback (increases 5-44%), three education + system change (average increase 6%), three education + system change + feedback (average 7.7% increase), one delayed testing. The conclusions are that only six RCTs were assessed at low risk of bias from both randomisation and attrition. Nevertheless, despite methodological shortcomings studies that found large changes (e.g. >20%) probably obtained real change.