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Objective: Timely cancer treatment improves survival and anxiety for some sites. Patients with esophageal cancer require specific workup before treatment, which can prolong the time from diagnosis to treatment (treatment interval [TI]). The geographical variation of this interval remains uninvestigated in patients with esophageal cancer. Methods: This retrospective population-level study conducted in Ontario used linked administrative health care databases. Patients treated for esophageal cancer between 2013 and 2018 were included. The TI was time from diagnosis to treatment. Patients were assigned a geographical Local Health Integration Network on the basis of postal code. Covariates included patient, disease, and diagnosing physician characteristics. Quantile regression modeled TI length at the 50th and 90th percentile and identified associated factors. Results: Of 7509 patients, 78% were male and most were aged between 60 and 69 years. The 50th and 90th percentile TI was 36 (interquartile range, 22-55) and 77 days, respectively. The difference between the Local Health Integration Network with the longest and shortest TI at the 50th and 90th percentile was 18 and 25 days, respectively. Older age (P

Patients with resectable esophageal cancer are recommended to undergo chemoradiotherapy before esophagectomy. A longer time to surgery (TTS) and/or time to consultation (TTC) may be associated with inferior cancer-related outcomes and heightened anxiety. Thoracic cancer surgery centers (TCSCs) oversee esophageal cancer management, but differences in TTC/TTS between centers have not yet been examined. This Ontario population-level study used linked administrative healthcare databases to investigate patients with esophageal cancer between 2013–2018, who underwent neoadjuvant chemoradiotherapy and then surgery. TTC and TTS were time from diagnosis to the first surgical consultation and then to surgery, respectively. Patients were assigned a TCSC based on the location of the surgery. Patient, disease, and diagnosing physician characteristics were investigated. Quantile regression was used to model TTS/TTC at the 50th and 90th percentiles and identify associated factors. The median TTS and TTC were 130 and 29 days, respectively. The adjusted differences between the TCSCs with the longest and shortest median TTS and TTC were 32 and 18 days, respectively. Increasing age was associated with a 16-day longer median TTS. Increasing material deprivation was associated with a 6-day longer median TTC. Significant geographic variability exists in TTS and TTC. Therefore, the investigation of TCSC characteristics is warranted. Shortening wait times may reduce patient anxiety and improve the control of esophageal cancer.

Abstract Background The 8th edition UICC/AJCC TNM8 (Tumour, Nodes, Metastasis) melanoma staging system introduced several modifications from the 7th edition (TNM7), resulting in changes in survival and subgroup composition. We set out to address the limited validation of TNM8 (stages I-IV) in large population-based datasets. Methods This retrospective cohort-study included 6,414 patients from the population-based Ontario Cancer Registry diagnosed with cutaneous melanoma between January 1, 2007 and December 31, 2012. Kaplan–Meier curves estimated the melanoma-specific survival (MSS) and overall survival (OS). Cox proportional hazard models were used to estimate adjusted hazard ratios for MSS and OS across stage groups. The Schemper-Henderson measure was used to assess the variance explained in the Cox regression. Results In our sample, 21.3% of patients were reclassified with TNM8 from TNM7; reclassifications in stage II were uncommon, and 44.1% of patients in stage III were reclassified to a higher subgroup. Minimal changes in MSS curves were observed between editions, but the stage IIB curve decreased and the stage IIIC curve increased. For TNM8, Stage I (n = 4,556), II (n = 1,206), III (n = 598), and IV (n = 54) had an estimated 5-year MSS of 98.4%, 82.5%, 66.4%, and 14.4%, respectively. Within stage III, IIIA 5-year MSS was 91.7% while stage IIID was 23.5%. HRs indicated that TNM8 more evenly separates subgroups once adjusted for patient- and disease-characteristics. The variance in MSS explained by TNM7 and TNM8 is 18.9% and 19.7%, respectively. Conclusion TNM8 performed well in our sample, with more even separation of stage subgroups and a modest improvement in predictive ability compared to TNM7.

Abstract The emergence of infections by carbapenem resistant Enterobacteriaceae (CRE) pathogens has created an urgent public health threat, as carbapenems are among the drugs of last resort for infections caused by a growing fraction of multi-drug resistant (MDR) bacteria. There is global consensus that new preventive and therapeutic strategies are urgently needed to combat the growing problem of MDR bacterial infections. Here, we report on the efficacy of a novel macrocyclic peptide, minimized theta-defensin (MTD)-12813 in CRE sepsis. MTD12813 is a theta-defensin inspired cyclic peptide that is highly effective against CRE pathogens K. pneumoniae and E. coli in vivo. In mouse septicemia models, single dose administration of MTD12813 significantly enhanced survival by promoting rapid host-mediated bacterial clearance and by modulating pathologic cytokine responses, restoring immune homeostasis, and preventing lethal septic shock. The peptide lacks direct antibacterial activity in the presence of mouse serum or in peritoneal fluid, further evidence for its indirect antibacterial mode of action. MTD12813 is highly stable in biological matrices, resistant to bacterial proteases, and nontoxic to mice at dose levels 100 times the therapeutic dose level, properties which support further development of the peptide as a first in class anti-infective therapeutic.

Objectives Regional variation in cancer survival is an important health system performance measurement. We evaluated if regional variation in colon cancer survival may be driven by differences in the patient population, their health and healthcare utilisation, and/or cancer care delivery.Design Population-based retrospective cohort study using routinely collected linked health administrative data.Setting Ontario, Canada.Participants Patients with colon cancer diagnosed between 1 January 2009 and 31 December 2012.Outcome Cancer-specific survival was compared across the province’s 14 health regions. Using accelerated failure time models, we assessed whether regional survival variations were mediated through differences in case mix, including age, sex, comorbidities, stage at diagnosis and colon subsite, potential marginalisation and/or prediagnosis healthcare.Results The study population included 16 895 patients with colon cancer. There was statistically significant regional variation in cancer-specific survival. Three regions had cancer-specific survival that was between 30% (95% CI 1.03 to 1.65) and 39% (95% CI 1.13 to 1.71) longer and one region had cancer-specific survival that was 26% shorter (95% CI 0.58 to 0.93) than the reference region. For three of these regions, case mix explained between 26% and 56% of the survival variation. Further adjustment for rurality explained 22% of the remaining survival variation in one region. Adjustment for continuity of primary care and the diagnostic interval length explained 10% and 11% of the remaining survival variation in two other regions. Socioeconomic marginalisation, recent immigration and colonoscopy history did not explain colon cancer survival variation.Conclusions Case mix accounted for much of the regional variation in colon cancer survival, indicating that efforts to monitor the quality of cancer care through survival metrics should consider case mix when reporting regional survival differences. Future work should repeat this approach in other settings and other cancer sites considering a broad range of potential mediators.

Abstract Background Advanced cancer stage at diagnosis may explain high cancer mortality among patients with a severe psychiatric illness (SPI). Studies to date investigating advanced stage cancer at diagnosis as a potential explanation for high cancer mortality in individuals with a history of mental illness have been inconclusive. We examined the relationship between a SPI history and unknown cancer stage at diagnosis in colorectal cancer (CRC) patients. Methods This was a population-based, cross-sectional study using linked administrative databases of CRC patients diagnosed between 01/04/2007 and 31/12/2012. Individuals who had a history of mental illness but did not meet the definition of a SPI were excluded. An SPI was measured in the 5 years prior to the cancer diagnosis and categorized as inpatient, outpatient or no SPI. Individuals with a best stage in Stage 0 to Stage IV were considered staged and absence of staging information was defined as unknown stage. The risk of unknown stage cancer was estimated using modified Poisson regression. Results The final study cohort included 24,507 CRC patients. 258 (1.1%) individuals experienced a history of inpatient SPI and 482 (2.0%) experienced outpatient SPI. After adjusting for confounders, CRC patients with an inpatient or outpatient history of SPI were at greater risk of having missing TNM stage at diagnosis, compared to patients with no history of a mental illness (RR 1.45 (95% CI: 1.14–1.85) and RR1.17 (95% CI 0.95–1.43), respectively). The results did not change when alternate practices to assign SPI history using administrative data were used. Conclusions Individuals with an SPI, especially those with a psychiatric admission, were more likely to have missing stage data compared to individuals without a history of a mental illness. Incomplete and low quality cancer staging data likely undermines the quality of cancer care following initial diagnosis. Understanding why patients with an SPI are missing this information is a critical first step to providing excellent care to this vulnerable population.

Abstract Background In order to maximize later health, there are established components and guidelines for quality follow-up care of breast cancer survivors. However, adherence to quality follow-up in Canada may not be optimal, and may vary by province. We determined and compared the proportion of patients in each province who received adherent and non-adherent surveillance for recurrence, new cancers and late effects, recommended preventive care, and recommended physician visits for comorbidities. Methods Cohorts consisted of all adult women diagnosed with incident invasive breast cancer between 2007 and 2010/2012 in four Canadian provinces (British Columbia (BC) N = 9338; Manitoba N = 2688; Ontario N = 23,700; Nova Scotia (NS) N = 2735), identified from provincial cancer registries, alive and cancer-free at 30 months post-diagnosis. Their healthcare utilization was determined from one to 5 years post-treatment, using linked administrative databases. Adherence, underuse, and overuse of recommended services were evaluated yearly and compared using descriptive statistics. Results In all provinces and follow-up years, the majority of survivors had more than the recommended number of visits to either an oncologist or primary care physician (range 53.8% NS Year 3; 85.8% Ontario Year 4). The proportion of patients with the guideline-recommended number of oncologist visits varied by province (range 29.8% BC Year 5; 74.8% Ontario Year 5), and the proportion of patients with less than the recommended number of specified breast cancer-related visits with either an oncologist or primary care physician ranged from 32.6% (Ontario Year 2) to 84.4% (NS Year 3). Underuse of surveillance breast imaging was identified in NS and BC. The proportion of patients receiving imaging for metastatic disease (not recommended in the guidelines) in BC, Manitoba, and Ontario (not reported in NS) ranged from 20.3% (BC Year 5) to 53.3% (Ontario Year 2). Compliance with recommended physician visits for patients with several chronic conditions was high in Ontario and NS. Preventive care was less than optimal in all provinces with available data. Conclusions Quality of breast cancer survivor follow-up care varies among provinces. Results point to exploration of factors affecting differences, province-specific opportunities for care improvement, and the value of administrative datasets for health system assessment.

Abstract Background The overuse of medical tests leads to higher costs, wasting of resources, and the potential for overdiagnosis of disease. This study was designed to determine whether the patients of family doctors who order more routine medical tests are diagnosed with more cancers. Method A retrospective population‐based cross‐sectional study using administrative health care data in Ontario Canada. We investigated the ordering of 23 routine laboratories and imaging tests 2008‐20012 by 6849 Ontario family physicians on their 4.9 million rostered adult patients. We compared physicians’ test utilization and calculated case‐mix adjusted observed to expected (O:E) utilization ratios to categorize physicians as Typical, Higher or Lower testers. Age‐sex standardized rates (cases/10 000 patient years) and Rate Ratios were determined for cancers of the thyroid, prostate, breast, lymphoma, kidney, melanoma, uterus, ovary, lung, esophagus, and pancreas for each tester group. Results There was wide variation in the use of the 23 tests by Ontario physicians. 26% and 24% of physicians were deemed Higher Testers for laboratory and imaging tests, while 41% and 38% were Typical Testers. The patients of higher test users were diagnosed with more cancers of thyroid (laboratory [RR 1.61, 95% CI 1.39‐1.87] and imaging [RR 2.08, 95% CI 0.88‐2.30]) and prostate (laboratory [RR 1.10, 95% CI 1.03‐1.18] and imaging [RR 1.05, 95% CI 1.00‐1.10]). Conclusion There is a wide variation in the ordering of routine and common medical tests among Ontario family doctors. The patients of higher testers were diagnosed with more thyroid and prostate cancers.

IntroductionThere is an evidence gap regarding the duration of SARS-CoV-2 shedding and of its variability across different care settings and by age, sex, income, and co-morbidities. Such evidence is part of understanding of infectivity and reinfection. We examine direct measures of viral shedding using a linked population-based health administrative dataset.MethodsLaboratory and sociodemographic databases for Ontario, Canada were linked to identify those testing positive (RT-PCR) between Jan. 15 and April 30, 2020 who underwent subsequent testing by May 31, 2020. To maximise use of available data, we computed two shedding duration estimates defined as the time between initial positive and most recent positive (documented shedding) or second of two negative tests (documented resolution). We also report multivariable results using quantile regression to examine subgroup differences.ResultsIn Ontario, of the 16,595 who tested positive before April 30, 2020, 6604 had sufficient subsequent testing to allow shedding duration calculation. Documented shedding median duration calculated in 4,889 (29% of 16,595) patients was 19 days (IQR 12-28). Documented resolution median duration calculated in 3,219 (19% of the 16,595) patients was 25 days (IQR 18-34). Long-term care residents had 3-5 day longer shedding durations using both definitions. Shorter documented shedding durations of 2-4 days were observed in those living in higher income neighbourhoods. Shorter documented resolution durations of 2-3 days were observed at the 25th% of the distribution in those aged 20-49. Only 11.5% of those with definitive negative test results reverted to negative status by day 14.ConclusionsViral shedding continued well beyond 14 days among this large subset of a population-based group with COVID-19, and longer still for long-term care residents and those living in less affluent neighborhoods. Our findings do not speak to duration of infectivity but are useful for understanding the expected duration of RT-PCR positivity and for identifying reinfection.

Introduction Despite recommendations, most studies examining health inequalities fail to report both absolute and relative summary measures. We examine colorectal cancer (CRC) survival for patients with and without severe psychiatric illness (SPI) to demonstrate the use and importance of relative and absolute effects. Objectives and Approach We conducted a retrospective cohort study of CRC patients diagnosed between 01/04/2007 and 31/12/2012, using linked administrative databases. SPI was defined as diagnoses of major depression, bipolar disorder, schizophrenia, and other psychotic illnesses six months to five years preceding cancer diagnosis and categorized as inpatient, outpatient or none. Associations between SPI history and risk of death were examined using Cox Proportional Hazards regression to obtain hazard ratios and Aalen’s semi-parametric additive hazards regression to obtain absolute differences. Both models controlled for age, sex, primary tumour location, and rurality. Results The final cohort included 24,507 CRC patients, 482 patients had an outpatient SPI history and 258 patients had an inpatient SPI history. 58.1% of patients with inpatient SPI history died, and 47.1% of patients with outpatient SPI history died. Patients with an outpatient SPI history had a 40% (HR 1.40, 95% CI: 1.22-1.59) increased risk of death and patients with an inpatient SPI history had a 91% increased risk of death (HR 1.91, 95% CI: 1.63-2.25), relative to no history of a mental illness. An outpatient SPI history was associated with an additional 33 deaths per 1000 person years, and an inpatient SPI was associated with an additional 82 deaths per 1000 person years after controlling for confounders. Conclusion / Implications We demonstrated that reporting of both relative and absolute effects is possible and calculating risk difference is relatively simple using Aalen models. We encourage future studies examining inequalities with time-to-event data to use this method and report both relative and absolute effect measures.

OBJECTIVES/GOALS: The “hidden curriculum” is a set of unofficial rules outside of the formal curriculum that allows medical students to succeed. It is often not accessible to those who are first-generation in medicine. This study created a novel survey tool to directly evaluate the hidden curriculum, its contributing factors, and its effects on students. METHODS/STUDY POPULATION: Using available literature as a guide, a novel survey tool to evaluate different aspects of the hidden curriculum was created. This survey consists of 17 Likert scale questions on topics varying from sense of belongingness to dress code, self-guided studying, mentorship, and confidence in knowing how to succeed. This survey tool was embedded into a larger survey evaluating health disparities and diversity, inclusion, accessibility, and justice (DEIAJ) in the curricular and extracurricular spaces. This survey packet was administered to all medical students at a large U.S. medical school. RESULTS/ANTICIPATED RESULTS: 166 medical students from all years responded to this survey. 70% were female, 27% male, and 3% non-binary or prefer not to say. 67% of respondents agreed or strongly agreed that there is a hidden curriculum accessible to only those who have family members in medicine. 57% agreed or strongly agreed that the medical school gave them the adequate training and resources to succeed. 48% agreed or strongly agreed that they would perform better academically if they had more money with 11% stating they often feel embarrassed in a professional setting due to lack of money. Fellow classmen, faculty members, and upperclassmen were identified as the most useful resources to learn how to succeed in medical school. Students on average reported feeling like they knew what to do to succeed in medical school half of the time. DISCUSSION/SIGNIFICANCE: This data strongly supports the existence of a hidden curriculum and gives insight into the importance of financial support for low-income students and peer support groups for those who do not have family members in medicine. This data will be used to inform future interventions to address the hidden curriculum.

Introduction: Breast cancer is detected through screening or through signs and symptoms. In Canada, mammograms for breast cancer screening are offered in organized programs or independently (opportunistic screening). Province of Ontario breast Diagnostic Assessment Units (DAUs) are facility-based programs that provide coordinated breast cancer diagnostic services, as opposed to usual care, in which the primary care provider arranges the tests and consultations. This study describes breast cancer detection method, diagnostic interval and DAU use across Ontario. Methods: The study cohort consisted of 6898 women with invasive breast cancer diagnosed in 2011. We used the Ontario Cancer Registry linked to administrative health care databases. We determined the detection method using the Ontario Breast Screening Program (OBSP) data and physician claims. The diagnostic interval was the time between the initial screen, specialist referral or first diagnostic test and the cancer diagnosis. The diagnostic route (whether through DAU or usual care) was determined based on the OBSP records and biopsy or surgery location. We mapped the diagnostic interval and DAU coverage geographically by women’s residence. Results: In 2011, 36% of Ontario breast cancer patients were screen-detected, with a 48% rate among those aged 50 to 69. The provincial median diagnostic interval was 32 days, with county medians ranging from 15 to 65 days. Provincially, 48.4% were diagnosed at a DAU, and this ranged from zero to 100% across counties. Conclusion: The screening detection rate in age-eligible breast cancer patients was lower than published population-wide screening rates. Geographic mapping of the diagnostic interval and DAU use reveals regional variations in cancer diagnostic care that need to be addressed.