Development and validation of a real-world model to predict 1-year Level 3 (severe) hypoglycaemia risk in adults with diabetes (the iNPHORM study, United States).

AIMS: We aimed to develop and internally validate a real-world prognostic model for Level 3 hypoglycaemia risk compatible with outpatient care in the United States. MATERIALS AND METHODS: iNPHORM is a 12-month, US-based panel survey. Adults (18-90 years old) with type 1 diabetes mellitus or insulin- and/or secretagogue-treated type 2 diabetes mellitus were recruited from a nationwide, probability-based internet panel. Among participants completing ≥ 1 follow-up questionnaire(s), we modelled 1-year Level 3 hypoglycaemia risk using Andersen and Gill's Cox survival and penalized regression with multiple imputation. Candidate variables were selected for their clinical relevance and ease of capture at point-of-care. RESULTS: In total, 986 participants [type 1 diabetes mellitus: 17%; men: 49.6%; mean age: 51 (SD: 14.3) years] were analysed. Across follow-up, 035.1 (95% CI: 32.2-38.1)% reported ≥1 Level 3 event(s), and the rate was 5.0 (95% CI: 4.1-6.0) events per person-year. Our final model showed strong discriminative validity and parsimony (optimism corrected c-statistic: 0.77). Numerous variables were selected: age; sex; body mass index; marital status; level of education; insurance coverage; race; ethnicity; food insecurity; diabetes type; glycated haemoglobin value; glycated haemoglobin variability; number, type and dose of various medications; number of SH events requiring hospital care (past year and over follow-up); type and number of comorbidities and complications; number of diabetes-related health care visits (past year); use of continuous/flash glucose monitoring; and general health status. CONCLUSIONS: iNPHORM is the first US-based primary prognostic study on Level 3 hypoglycaemia. Future model implementation could potentiate risk-tailored strategies that reduce real-world event occurrence and overall diabetes burden.

Severe (level 3) hypoglycaemia occurrence in a real-world cohort of adults with type 1 or 2 diabetes mellitus (iNPHORM, United States).

AIMS: Among adults with insulin- and/or secretagogue-treated diabetes in the United States, very little is known about the real-world descriptive epidemiology of iatrogenic severe (level 3) hypoglycaemia. Addressing this gap, we collected primary, longitudinal data to quantify the absolute frequency of events as well as incidence rates and proportions. MATERIALS AND METHODS: iNPHORM is a US-wide, 12-month ambidirectional panel survey (2020-2021). Adults with type 1 diabetes mellitus (T1DM) or insulin- and/or secretagogue-treated type 2 diabetes mellitus (T2DM) were recruited from a probability-based internet panel. Participants completing ≥1 follow-up questionnaire(s) were analysed. RESULTS: Among 978 respondents [T1DM 17%; mean age 51 (SD 14.3) years; male: 49.6%], 63% of level 3 events were treated outside the health care system (e.g. by family/friend/colleague), and <5% required hospitalization. Following the 12-month prospective period, one-third of individuals reported ≥1 event(s) [T1DM 44.2% (95% CI 36.8%-51.8%); T2DM 30.8% (95% CI 28.7%-35.1%), p = .0404, α = 0.0007]; and the incidence rate was 5.01 (95% CI 4.15-6.05) events per person-year (EPPY) [T1DM 3.57 (95% CI 2.49-5.11) EPPY; T2DM 5.29 (95% CI 4.26-6.57) EPPY, p = .1352, α = 0.0007]. Level 3 hypoglycaemia requiring non-transport emergency medical services was more common in T2DM than T1DM (p < .0001, α = 0.0016). In total, >90% of events were experienced by <15% of participants. CONCLUSIONS: iNPHORM is one of the first long-term, prospective US-based investigations on level 3 hypoglycaemia epidemiology. Our results underscore the importance of participant-reported data to ascertain its burden. Events were alarmingly frequent, irrespective of diabetes type, and concentrated in a small subsample.

Printed educational materials directed at Ontario family physicians do not improve adherence to guideline recommendations for diabetes management: a pragmatic, factorial, cluster randomized controlled trial [ISRCTN72772651].

BACKGROUND: Printed educational materials (PEMs) have long been used to inform clinicians on evidence-based practices. However, the evidence for their effects on patient care and outcomes is unclear. In Ontario, despite widely available clinical practice guidelines recommending antihypertensives and cholesterol-lowering agents for patients with diabetes, prescriptions remain low. We aimed to determine whether PEMs can influence physicians to intensify prescribing of these medications. METHODS: A pragmatic, 2 × 2 factorial, cluster randomized controlled trial was designed to ascertain the effect of two PEM formats on physician prescribing: a postcard-sized message ("outsert") or a longer narrative article ("insert"). Ontario family physician practices (clusters) were randomly allocated to receive the insert, outsert, both or neither. Physicians were eligible if they were in active practice and their patients were included if they were over 65 years with a diabetes diagnosis; both were unaware of the trial. Administrative databases at ICES (formerly the Institute for Clinical Evaluative Sciences) were used to link patients to their physician and to analyse prescribing patterns at baseline and 1 year following PEM mailout. The primary outcome was intensification defined as the addition of a new antihypertensive or cholesterol-lowering agent, or dose increase of a current drug, measured at the patient level. Analyses were by intention-to-treat and accounted for the clustering of patients to physicians. RESULTS: We randomly assigned 4231 practices (39% of Ontario family physicians) with a total population of 185,526 patients (20% of patients with diabetes in Ontario primary care) to receive the insert, outsert, both, and neither; among these, 4118 practices were analysed (n = 1025, n = 1037, n = 1031, n = 1025, respectively). No significant treatment effect was found for the outsert (odds ratio (OR) 1.01, 95% confidence interval (CI) 0.98 to 1.04) or the insert (OR 0.99, 95% CI 0.96 to 1.02). Percent of intensification in the four arms was similar (approximately 46%). Adjustment for physician characteristics (e.g., age, sex, practice location) had no impact on these findings. CONCLUSIONS: PEMs have no effect on physician's adherence to recommendations for the management of diabetes-related complications in Ontario. Further research should investigate the effect of other strategies to narrow this evidence-to-practice gap. TRIAL REGISTRATION: ISRCTN72772651 . Retrospectively registered 21 July 2005.

Selective Laser Trabeculoplasty versus Argon Laser Trabeculoplasty in Glaucoma Patients Treated Previously with 360° Selective Laser Trabeculoplasty: A Randomized, Single-Blind, Equivalence Clinical Trial.

PURPOSE: The effectiveness of selective laser trabeculoplasty (SLT) was compared with argon laser trabeculoplasty (ALT) in a randomized clinical trial for patients with medically uncontrolled open-angle glaucoma who have previously received 360° SLT. DESIGN: An active equivalence parallel armed randomized control trial. PARTICIPANTS: Patients with open-angle glaucoma including pigmentary dispersion syndrome and pseudoexfoliation syndrome were enrolled into the study from 7 different sites across Canada. METHODS: One setting of 180° of either SLT or ALT was assigned randomly and applied to each participant. MAIN OUTCOME MEASURES: The change in intraocular pressure (IOP) from baseline to 12 months was compared between the 2 groups. RESULTS: A total of 132 patients were recruited, 2 of which dropped out early in the study, leaving 130 patients who completed the study as per protocol. For those, the study's primary outcome was calculated. The IOP change at 1 year in comparison to baseline for SLT vs. ALT was found to be different by 0.33 mmHg between the 2 groups (3.16 for SLT and 2.83 for ALT) and was not statistically significant (P = 0.71) Further analysis, though, showed that SLT had a significantly lower IOP reduction at early time points: 1 week and 1 month, but this effect was lost by 3 months. Corresponding to this finding was the strong trend for ALT to fail more quickly than SLT. Although repeatable, the first repeat SLT reduced IOP to only about half compared with initial SLT treatment. CONCLUSIONS: The comparison at 12 months following the laser therapy showed that both modalities lowered the IOP with approximately 3 mmHg, yet essentially all of the time-to-failure analyses favored SLT over ALT. The repeat SLT effect was found to be half of the initial treatment.

Untreated illness and recovery in clients of an early psychosis intervention program: a 10-year prospective cohort study.

PURPOSE: To investigate whether duration of untreated psychosis (DUP) and duration of untreated illness (DUI) are associated with measures of both subjective and objective recovery 10 years after a first episode of psychosis. METHODS: A cohort of 65 clients from an early psychosis intervention program completed a battery of outcome measures 10 years following initial treatment for first-episode psychosis (FEP). The outcomes of interest were self-perceived recovery scores (Maryland Assessment of Recovery in People with Serious Mental Illness Scale) and occupational activity, defined as engagement in work and/or school on a full/part-time basis. Multiple linear and logistic regression analyses were used to estimate the associations between DUP and DUI with each measure of recovery, adjusting for potential confounding factors. RESULTS: We did not find a statistically significant association between DUP and either occupational activity (OR = 1.26, 95% CI 0.81-1.95) or self-perceived recovery score (ß = - 0.73, 95% CI - 2.42 to 0.97). However, we found a significant negative association between DUI and self-perceived recovery score (ß = - 0.52, 95% CI - 0.87 to - 0.16). CONCLUSIONS: Our findings suggest that DUI may have a stronger influence than DUP on recovery from FEP at 10-year follow-up. This suggests the potential value in targeted interventions for people with a long DUI to increase the likelihood of achieving recovery after the first episode of psychosis.

On the estimation of intracluster correlation for time-to-event outcomes in cluster randomized trials.

Cluster randomized trials (CRTs) involve the random assignment of intact social units rather than independent subjects to intervention groups. Time-to-event outcomes often are endpoints in CRTs. Analyses of such data need to account for the correlation among cluster members. The intracluster correlation coefficient (ICC) is used to assess the similarity among binary and continuous outcomes that belong to the same cluster. However, estimating the ICC in CRTs with time-to-event outcomes is a challenge because of the presence of censored observations. The literature suggests that the ICC may be estimated using either censoring indicators or observed event times. A simulation study explores the effect of administrative censoring on estimating the ICC. Results show that ICC estimators derived from censoring indicators or observed event times are negatively biased. Analytic work further supports these results. Observed event times are preferred to estimate the ICC under minimum frequency of administrative censoring. To our knowledge, the existing literature provides no practical guidance on the estimation of ICC when substantial amount of administrative censoring is present. The results from this study corroborate the need for further methodological research on estimating the ICC for correlated time-to-event outcomes. Copyright © 2016 John Wiley & Sons, Ltd.

Effectiveness of Nonmydriatic Ultra-Widefield Retinal Imaging to Screen for Diabetic Eye Disease: A Randomized Controlled Trial (Clearsight).

OBJECTIVE: Suboptimal diabetic eye disease screening is a major cause of preventable vision loss. Screening barriers include mydriasis and the need for dedicated screening appointments. The Clearsight trial assessed whether nonmydriatic ultra-widefield (NM UWF) screening on the day of a diabetes clinic visit improved detection of clinically important eye disease versus usual screening. RESEARCH DESIGN AND METHODS: This single-center, randomized, parallel-group controlled trial was conducted at St. Joseph's Health Care, London, Ontario, Canada. Adults with diabetes due for screening were randomized to same-day, on-site screening (NM UWF imaging) on the day of a scheduled diabetes clinic visit or usual screening (encouraged to arrange optometrist screening). The primary outcome was detection of actionable eye disease (AED), defined as the need for an ophthalmology referral or increased ocular surveillance. The primary analysis (modified intention-to-screen) compared the proportions of AED between groups within 1 year of enrollment. RESULTS: Of 740 participants randomized between 7 March 2016 and 17 April 2019, 335 on-site screening and 323 usual screening participants met criteria for the primary analysis. More AED was detected in the on-site screening group than in the usual screening group (50 of 335 [14.9%] vs. 22 of 323 [6.8%]; adjusted odds ratio 2.51; 95% CI 1.49-4.36). The number needed to screen by on-site screening in order to detect 1 additional patient with AED was 13 (95% CI 8-29). CONCLUSIONS: Same-day, on-site screening by NM UWF imaging increased the detection of clinically important diabetic eye disease versus usual screening. Integration of NM UWF imaging into routine diabetes clinic visits improved screening adherence and has the potential to prevent vision loss.

Does Shiftwork Impact Cognitive Performance? Findings from the Canadian Longitudinal Study on Aging (CLSA).

Few large nationwide studies have investigated the relationship between shiftwork and cognitive performance, and little is known about whether and how psychological distress may impact this relationship. This study aimed to examine: (1) the cross-sectional relationship between shiftwork (yes/no) and some aspects of cognitive performance (declarative memory and executive functioning) and (2) the potential moderating effect of psychological distress among 20,610 community-dwelling adults from the comprehensive cohort of the Canadian Longitudinal Study on Aging (CLSA). Differences by sex and retirement status were also explored. Shiftwork was significantly associated with poorer performance for executive functioning (interference condition: ß = 0.47, 95% CI: 0.31 to 0.63; MAT: ß = -0.85, 95% CI: -1.21 to -0.50) but not for declarative memory. Completely and not/partly retired males showed poorer cognitive performance on executive functioning. However, no evidence of a moderating effect by psychological distress was found. Our findings confirm the association between shiftwork and cognitive performance and highlight important health correlates of shiftwork.

The quality of modern cross-sectional ecologic studies: a bibliometric review.

The ecologic study design is routinely used by epidemiologists in spite of its limitations. It is presently unknown how well the challenges of the design are dealt with in epidemiologic research. The purpose of this bibliometric review was to critically evaluate the characteristics, statistical methods, and reporting of results of modern cross-sectional ecologic papers. A search through 6 major epidemiology journals identified all cross-sectional ecologic studies published since January 1, 2000. A total of 125 articles met the inclusion requirements and were assessed via common evaluative criteria. It was found that a considerable number of cross-sectional ecologic studies use unreliable methods or contain statistical oversights; most investigators who adjusted their outcomes for age or sex did so improperly (64%), statistical validity was a potential issue for 20% of regression models, and simple linear regression was the most common analytic approach (31%). Many authors omitted important information when discussing the ecologic nature of their study (31%), the choice of study design (58%), and the susceptibility of their research to the ecological fallacy (49%). These results suggest that there is a need for an international set of guidelines that standardizes reporting on ecologic studies. Additionally, greater attention should be given to the relevant biostatistical literature.

Application of a fall screening algorithm stratified fall risk but missed preventive opportunities in community-dwelling older adults: a prospective study.

OBJECTIVES: Evaluate the ability of the American and British Geriatrics Society fall prevention guideline's screening algorithm to identify and stratify future fall risk in community-dwelling older adults. METHODS: Prospective cohort of community-dwelling older adults (n = 117) aged 65 to 90 years. Fall history, balance, and gait measured during a comprehensive geriatric assessment at baseline. Falls data were collected monthly for 1 year. The outcomes of any fall and any injurious fall were evaluated. RESULTS: The algorithm stratified participants into 4 hierarchal risk categories. Fall risk was 33% and 68% for the "no intervention" and "comprehensive fall evaluation required" groups respectively. The relative risk estimate for falling comparing participants in the 2 intervention groups was 2.08 (95% CI 1.42-3.05) for any fall and 2.60 (95% Cl 1.53-4.42) for any injurious fall. Prognostic accuracy values were: sensitivity of 0.50 (95% Cl 0.36-0.64) and specificity of 0.82 (95% CI 0.70-0.90) for any fall; and sensitivity of 0.56 (95% CI 0.38-0.72) and specificity of 0.78 (95% Cl 0.67-0.86) for any injurious fall. CONCLUSIONS: The algorithm was able to identify and stratify fall risk for each fall outcome, though the values of prognostic accuracy demonstrate moderate clinical utility. The recommendations of fall evaluation for individuals in the highest risk groups appear supported though the recommendation of no intervention in the lowest risk groups may not address their needs for fall prevention interventions. Further evaluation of the algorithm is recommended to refine the identification of fall risk in community-dwelling older adults.

Relationships between sleep and internalizing problems in early adolescence: Results from Canadian National Longitudinal Survey of Children and Youth.

BACKGROUND: Both inadequate sleep and internalizing problems, such as symptoms of anxiety and depression, are prevalent among adolescents with sparse epidemiological literature outlining sex-specific relationships at this critical age. OBJECTIVE: To examine cross-sectional and prospective relationships between self-reported sleep problems, indicated by sleep duration, difficulties getting to sleep and changes in difficulties getting to sleep with internalizing problems in early adolescence. METHODS: This study was a secondary analysis of data from the Canadian National Longitudinal Survey of Children and Youth. Multivariable linear regression was used to estimate cross-sectional and longitudinal associations. Relevant family and social context variables were controlled for in multivariable analyses. Family functioning was assessed as a potential effect modifier. RESULTS: There were 993 and 736 participants [longitudinal cohort entry age of 10 or 11 years; 49% male] in longitudinal and cross-sectional analyses, respectively. Most cross-sectional multivariable analyses of sleep duration and internalizing problems revealed no statistical associations. Difficulties sleeping and concurrent internalizing problems were positively associated in 12/13 year old females (ß = 1.77 [0.94, 2.61], R2 = 17%) and males (ß = 1.18 [0.36, 2.01], R2 = 16%). High persistent difficulties sleeping in females aged 12/13 to 14/15 years also positively predicted internalizing problems in females age 14/15 years (ß = 1.90 [0.52, 3.29], R2 = 21%) while controlling for initial internalizing symptoms. Family functioning was not found to be an effect modifier. CONCLUSION: Findings highlight the potential role of difficulties sleeping for adolescents' mental health. Public health initiatives to promote sleep hygiene in this population subgroup are critical to prevent the potential long-term health impact of sleep problems.

Effect of a Community Health Worker-Delivered Parental Education and Counseling Intervention on Anemia Cure Rates in Rural Indian Children: A Pragmatic Cluster Randomized Clinical Trial.

IMPORTANCE: Iron deficiency anemia, the largest cause of anemia worldwide, adversely affects cognitive development in children. Moreover, the imperceptible childhood anemia prevalence reduction in response to anemia control measures is associated with tremendous social and economic cost. OBJECTIVE: To evaluate the effects of community-based parental education/counseling when combined with usual treatment on children's anemia cure rate. DESIGN, SETTING, AND PARTICIPANTS: A pragmatic cluster randomized clinical trial in children aged 12 to 59 months from 55 villages from the rural Chamrajnagar district in southern India was conducted between November 2014 and July 2015; 6-month follow-up ended in January 2016. Villages were randomly assigned to either usual treatment (n = 27) or to the intervention (n = 28). Among 1144 participating children, 534 were diagnosed as having anemia (hemoglobin levels <11 g/dL and >7.9 g/dL; to convert to grams per liter, multiply by 10) and constituted the study sample in this analysis. Data were analyzed between July 2016 and September 2017. INTERVENTIONS: Iron and folic acid (IFA), 20 mg/d, 5 times daily per week, for 5 months (usual treatment) or health worker-delivered education/counseling combined with usual treatment (intervention). MAIN OUTCOMES AND MEASURES: The primary outcome was anemia cure rate defined as hemoglobin level at or greater than 11 g/dL during follow-up. RESULTS: Of the children included in the study, the mean age was 30 months, with a slightly higher ratio of boys to girls. Of 534 children with anemia (intervention n = 303; usual treatment n = 231), 517 were reassessed after 6 months (intervention n = 298; usual treatment n = 219) while 17 were lost to follow-up (intervention n = 5 and usual treatment n = 12). Anemia cure rate was higher in children in the intervention group compared with children receiving usual treatment (55.7% [n = 166 of 298] vs 41.4% [n = 90 of 219]). The risk ratio derived through multilevel logistic regression was 1.37 (95% CI, 1.04-1.70); the model-estimated risk difference was 15.1% (95% CI, 3.9-26.3). Intervention-group children demonstrated larger mean hemoglobin increments (difference, intervention vs control: 0.25 g/dL; 95% CI, 0.07-0.44 g/dL) and improved IFA adherence (61.7%; 95% CI, 56.2-67.3 vs 48.4%; 95% CI, 41.7-55.1 consumed >75% of tablets provided). Adverse events were mild (intervention: 26.8%; 95% CI, 21.8-31.9 vs usual treatment: 21%; 95% CI, 15.6-26.4). To cure 1 child with anemia, 7 mothers needed to be counseled (number needed to treat: 7; 95% CI, 4-26). CONCLUSIONS AND RELEVANCE: Parental education and counseling by a community health worker achieved perceivable gains in curing childhood anemia. Policy makers should consider this approach to enhance population level anemia control. TRIAL REGISTRATION: ISRCTN identifier: ISRCTN68413407.

Association of Arthritis Onset with Influenza: Analysis of the Canadian Early Inflammatory Arthritis Cohort.

OBJECTIVE: To evaluate seasonal patterns of early inflammatory arthritis (IA) onset and potential associations with IA symptom onset. METHODS: The Canadian Early Arthritis Cohort (CATCH) is an inception cohort study of adults with early (12 months or less) IA. We used patient reports of symptom onset as a proxy of IA onset and examined the seasonal distribution of IA onset over 10 years. Influenza time series was based on laboratory-confirmed influenza A and B from the Canadian FluWatch surveillance from 2010-2016. Bivariate analysis of influenza and IA was performed using cross-correlations with different time lags and Poisson regression. IA and influenza were recorded as monthly total frequencies. RESULTS: Of 2519 IA patients, 88% had confirmed rheumatoid arthritis (RA). Significantly, more IA onsets occurred in winter compared with other seasons (P = 0.03); although IA onset was more frequent in January, the difference between months was not statistically significant. Compared to months with the lowest influenza rates, months with the highest influenza rates had a statistically significant, but trivial, increase of 0.003% in the incidence of IA (incidence rate ratio (95% confidence interval): 1.00003 (1.00005; 1.000053), P = 0.02). CONCLUSION: Although IA symptom onset occurs more frequently in winter, we found that flu outbreaks were not associated with a meaningful increase in IA symptom onset in a large, well-characterized cohort of Canadian adults over 6 years.

Imputation strategies for missing continuous outcomes in cluster randomized trials.

In cluster randomized trials, intact social units such as schools, worksites or medical practices - rather than individuals themselves - are randomly allocated to intervention and control conditions, while the outcomes of interest are then observed on individuals within each cluster. Such trials are becoming increasingly common in the fields of health promotion and health services research. Attrition is a common occurrence in randomized trials, and a standard approach for dealing with the resulting missing values is imputation. We consider imputation strategies for missing continuous outcomes, focusing on trials with a completely randomized design in which fixed cohorts from each cluster are enrolled prior to random assignment. We compare five different imputation strategies with respect to Type I and Type II error rates of the adjusted two-sample t -test for the intervention effect. Cluster mean imputation is compared with multiple imputation, using either within-cluster data or data pooled across clusters in each intervention group. In the case of pooling across clusters, we distinguish between standard multiple imputation procedures which do not account for intracluster correlation and a specialized procedure which does account for intracluster correlation but is not yet available in standard statistical software packages. A simulation study is used to evaluate the influence of cluster size, number of clusters, degree of intracluster correlation, and variability among cluster follow-up rates. We show that cluster mean imputation yields valid inferences and given its simplicity, may be an attractive option in some large community intervention trials which are subject to individual-level attrition only; however, it may yield less powerful inferences than alternative procedures which pool across clusters especially when the cluster sizes are small and cluster follow-up rates are highly variable. When pooling across clusters, the imputation procedure should generally take intracluster correlation into account to obtain valid inferences; however, as long as the intracluster correlation coefficient is small, we show that standard multiple imputation procedures may yield acceptable type I error rates; moreover, these procedures may yield more powerful inferences than a specialized procedure, especially when the number of available clusters is small. Within-cluster multiple imputation is shown to be the least powerful among the procedures considered.

Lipoprotein(a) and secondary prevention of atherothrombotic events: A critical appraisal.

Elevated plasma concentrations of lipoprotein(a) [Lp(a)] are an independent, and possibly causal, risk factor for atherothrombotic diseases including coronary heart disease. The principal evidence base for this comes from large population studies focusing on first atherothrombotic events. However, inconsistent findings have been reported from studies investigating the impact of elevated Lp(a) on atherothrombotic events in subjects with preexisting cardiovascular disease. This question is very important because the secondary prevention population is recommended for Lp(a) screening by some guidelines and could be an important target group for Lp(a)-lowering therapies that are currently on the horizon. In this review, we survey the secondary prevention literature as it relates to Lp(a) and identify some possible confounding factors that may underlie the inconsistent findings, such as index event bias.

A randomised trial of non-mydriatic ultra-wide field retinal imaging versus usual care to screen for diabetic eye disease: rationale and protocol for the Clearsight trial.

INTRODUCTION: Suboptimal screening for diabetic eye disease is a major cause of preventable vision loss. Screening barriers include mydriasis and the extra time patients need to attend dedicated eye screening appointments. In the Clearsight trial, we are testing whether screening by non-mydriatic ultra-wide field (NM UWF) imaging on the day patients attend their diabetes outpatient clinic visit improves detection of clinically important eye disease compared with usual screening. METHODS AND ANALYSIS: Patients with diabetes due for a screening eye exam by the 2013 Canadian Diabetes Association (CDA) practice guidelines are being randomised to on-site screening by NM UWF imaging on the day of their clinic visit or to usual screening where, per CDA guidelines, they are encouraged to arrange an exam by an optometrist. The primary outcome is actionable eye disease (AED) based on a need for referral to ophthalmology and/or increased ocular surveillance. The primary analysis will use an intention-to-screen approach that compares the proportions of detected AED between on-site and usual screening groups under a superiority hypothesis in favour of on-site screening. With 740 randomised participants, the study will have 80% power to detect ≥5% absolute increase in the AED rate among on-site screening versus usual screening participants. This difference translates into a number-needed-to-screen by on-site screening of 20 to detect 1 additional person with AED. ETHICS AND DISSEMINATION: The protocol was approved by the institutional review board of Western University. The findings of the trial will be disseminated directly to participants and through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: ClinicalTrials.Gov NCT02579837 (registered 16 October 2015). PROTOCOL ISSUE DATE: 18 November 2015.

Influence of patterns of hormone replacement therapy use and mammographic density on breast cancer detection.

BACKGROUND: There is evidence that factors such as current hormone replacement therapy (HRT) use and mammographic density may each lower the sensitivity of mammography and are associated with a greater risk of developing an interval cancer. This study explores this relationship further by examining the influence of patterns of HRT use and the percentage of mammographic density on the detection of breast cancer by classification of interval cancer. METHODS: This study uses a case-case design nested within a cohort of women screened by the Ontario Breast Screening Program between 1994 and 2002. Interval cancers, both those missed at screening but seen on retrospective review (n = 87) or true intervals without visible tumor signs at screening (n = 288) were matched to 450 screen-detected cancers. The association between the percentage of mammographic density, measured by radiologists and a computer-assisted method, and HRT use, ascertained from a mailed questionnaire, and the risk of being diagnosed with an interval cancer was estimated using conditional logistic regression. RESULTS: A monotonic gradient of increasing risk for interval cancers was found for each 25% increase in mammographic density [odds ratio (OR), 1.77; 95% confidence intervals (95% CI), 1.07-2.95 for missed intervals and OR, 2.16; 95% CI, 1.59-2.94 for true intervals]. After adjusting for mammographic density, a significantly increased risk for true-interval cancers remained for women taking estrogen alone (OR, 1.75; 95% CI, 1.11-2.83) as well as for missed- (OR, 2.84; 95% CI, 1.32-6.13) and true-interval cancers (OR, 1.79; 95% CI, 1.10-2.90) for women taking combined HRT. CONCLUSIONS: Information on mammographic density and HRT use should routinely be collected at the time of screening. Women at risk should be made aware of the lower sensitivity of mammography and offered alternative procedures for screening.

A blended knowledge translation initiative to improve colorectal cancer staging [ISRCTN56824239].

BACKGROUND: A significant gap has been documented between best practice and the actual practice of surgery. Our group identified that colorectal cancer staging in Ontario was suboptimal and subsequently developed a knowledge translation strategy using the principles of social marketing and the influence of expert and local opinion leaders for colorectal cancer. METHODS/DESIGN: Opinion leaders were identified using the Hiss methodology. Hospitals in Ontario were cluster-randomized to one of two intervention arms. Both groups were exposed to a formal continuing medical education session given by the expert opinion leader for colorectal cancer. In the treatment group the local Opinion Leader for colorectal cancer was detailed by the expert opinion leader for colorectal cancer and received a toolkit. Forty-two centres agreed to have the expert opinion leader for colorectal cancer come and give a formal continuing medical education session that lasted between 50 minutes and 4 hours. No centres refused the intervention. These sessions were generally well attended by most surgeons, pathologists and other health care professionals at each centre. In addition all but one of the local opinion leaders for colorectal cancer met with the expert opinion leader for colorectal cancer for the academic detailing session that lasted between 15 and 30 minutes. DISCUSSION: We have enacted a unique study that has attempted to induce practice change among surgeons and pathologists using an adapted social marketing model that utilized the influence of both expert and local opinion leaders for colorectal cancer in a large geographic area with diverse practice settings.

Etiologic and other factors predicting nevus-associated cutaneous malignant melanoma.

Cutaneous malignant melanomas with histologic evidence of an associated nevus (N+) may have a different risk factor profile from that of melanomas without it (N-). To address this question, a case-only analysis of 932 people with cutaneous malignant melanoma was done to identify etiologic and other factors associated with N+ melanoma. Evidence of an associated nevus was found in 36% of melanomas. N+ melanomas were thinner (Ptrend=0.0009) and more likely to be of the superficial spreading type than other types of melanoma. Subjects with N+ melanomas were younger (Ptrend<0.0001) and reported a higher nevus density on their skin than subjects with N- melanomas [odds ratio (OR), 3.1; 95% confidence interval (CI), 1.6-6.0, for high nevus density versus no nevi]. Indicators of high accumulated sun exposure were less prevalent among subjects with N+ melanomas (OR, 0.3; 95% CI, 0.2-0.4, for melanoma location on the head and neck versus location on trunk; OR, 0.2; 95% CI, 0.1-0.4, for severe solar elastosis adjacent to the melanoma versus no elastosis; OR, 0.2; 95% CI, 0.1-0.4, for lentigo maligna melanoma subtype versus superficial spreading subtype). With the exception of solar elastosis and age, all of the aforementioned variables remained significantly associated with N+ melanomas in multivariate analyses. No associations with self-reported measures of sun exposure, sunburn, or pigmentation phenotype were apparent. Our findings provide some support for the hypothesis of etiologically separate pathways for melanoma, with N+ melanomas appearing less likely to develop in the presence of characteristics suggesting high accumulated sun exposure than N- melanomas. However, it is possible that high UV exposure causes involution of nevi, thus reducing the density of nevi in exposed skin and thereby the probability of N+ melanoma.

Comparison of papanicolaou (Pap) test rates across Ontario and factors associated with cervical screening.

BACKGROUND: Cervical cancer remains a significant yet preventable disease despite the widespread availability of Pap test screening, which detects cervical cancer and its precursor lesions. The aims of this study were to: i) estimate and compare age- and hysterectomy-adjusted Pap test rates across the 37 Ontario public health units (PHUs), and ii) explore the association between several factors and Pap test rates (at the ecological level). METHODS: Cytobase, an Ontario Pap test registry, captures more than 80% of all Pap tests in Ontario. Cytobase was used to determine Pap test rates adjusted for age, hysterectomy and Cytobase coverage for the year 2001. Multiple linear regression analyses were used to evaluate the relationship between Pap test rates and various factors at an ecological level, RESULTS: Age-, hysterectomy- and Cytobase-adjusted one-year Pap rates ranged from 11.6% to 73.9% among PHUs. The overall rate for Ontario was 40.7%. Multivariate analyses indicated that the presence of a teaching hospital was associated with higher Pap test rates. CONCLUSION: One-year Pap test rates varied greatly across the 37 public health units in Ontario. Pap test rates determined using Cytobase were lower than self-reported rates obtained from the Canadian Community Health Survey, possibly due to "over-reporting". In general, women were not screened as frequently as recommended by the Ontario Cervical Screening Program. A positive association was observed between Pap test rates and the presence of a teaching hospital. Data quality issues limit the ability to monitor cervical screening. A provincial registry would address these issues.