Improving Students Access to Primary Health Care Through School-Based Health Centers.

BACKGROUND: More than 20 million children in the United States lack access to primary health care. PRACTICE LEARNING: Research shows that students with regular access to physical and mental health services have fewer absences, are more social, less likely to participate in risky behaviors, have improved focus and higher test scores. IMPLICATION FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: School-based health centers (SBHCs) can be an important, valuable and viable health care delivery option to meet the full-range of primary health care needs of students where they spend the majority of their wake hours, ie, in school. Children in rural and other underserved communities, as well as those underinsured, non-insured, economically challenged, underserved, and the most vulnerable among us are especially at risk. CONCLUSIONS: This paper discusses the history, value, and importance of SBHCs from myriad perspectives, including physical and emotional wellbeing, academic and social success, and the promotion of a positive transition to adulthood. In addition, the authors' experiences that resulted in building the first SBHC in the Mid-Hudson Valley Region of New York State are shared. These experiences form the foundation for creating an important roadmap for individuals and school leaders that are interested in bringing a SBHC to their school and district.

Determining the Associations Between Glucocorticoid Use During Hematologic Chemotherapy Treatment and New-onset Diabetes and Hyperglycemia and Mortality: A Population-based Cohort Study.

OBJECTIVES: The aim of this study was to determine the associations between glucocorticoid administration during chemotherapy for hematologic malignancy and hyperglycemia, new-onset diabetes, and mortality in Ontario, Canada. Hospitalization and emergency room utilization during the chemotherapy treatment period were also described. METHODS: We conducted a retrospective cohort study using health administrative data from ICES, Ontario, to assess risk of new-onset diabetes, new-onset hyperglycemia, and hyperglycemia for individuals with leukemia, non-Hodgkin lymphoma (NHL), and Hodgkin lymphoma (HL) receiving glucocorticoids during chemotherapy between 2006 and 2016. Using multivariable regression models, we determined the associations between glucocorticoid exposure and our outcomes of interest, controlling for age, sex, marginalization, and comorbidities. RESULTS: Our cohort included 19,530 individuals; 71.1% (n=13,893) received a glucocorticoid. The highest proportion of hyperglycemia occurred with leukemia (25.4%, n=1,301). Of the 15,580 individuals with no history of diabetes, those with leukemia had the highest rate of new-onset diabetes (7.1%, n=279) and new-onset hyperglycemia (18.1%, n=641), and glucocorticoid exposure increased the risk of new-onset diabetes (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.01 to 1.64, p=0.04) and new-onset hyperglycemia (HR 1.28, 95% CI 1.09 to 1.5, p=0.003). Hyperglycemia during chemotherapy increased the risk of all-cause mortality for the combined (HR 1.18, 95% CI 1.09 to 1.27, p<0.0001) and NHL (HR 1.16, 95% CI 1.04 to 1.28, p=0.007) cohorts. CONCLUSIONS: Hyperglycemia is common during hematologic chemotherapy treatment and is associated with a modest increased risk of all-cause mortality. Routine screening, monitoring, and management of hyperglycemia should be an integral part of treatment plans for leukemia, NHL, or HL, with or without glucocorticoid administration.

Von Willebrand Factor (VWF) multiplex activity assay differentiation of type 1 von Willebrand Disease (VWD) and variant VWD.

INTRODUCTION: VWD diagnosis is challenging requiring multiple VWF activity tests using many individual assays. We have developed an ELISA-based VWF Multiplex Activity Assay (VWF-MAA) to address this concern; however, the ability of the VWF-MAA to discriminate between type 1 VWD, variant VWD, and normal subjects has not been evaluated. AIM: To evaluate the VWF-MAA and its ability to differentiate between type 1 VWD, variant VWD and normal subjects in individuals undergoing an initial laboratory evaluation for bleeding. METHODS: A total of 177 plasma samples from the Zimmerman Program: Comparative Effectiveness in the Diagnosis of VWD were evaluated from 11 centres across the US and Canada. The VWF-MAA was compared to Versiti Blood Research Institute (VBRI) and Local Center (LC) assigned VWD diagnosis. RESULTS: Overall, 129/177 (72.9%) were correctly assigned as normal (non-VWD), type 1, or variant VWD compared to the VBRI assigned diagnosis. VWF-MAA assigned non-VWD accurately in 29/57 (50.9%) samples, and type 1 VWD accurately in 93/110 (84.6%) samples. Considering LC diagnosis where there was agreement with VWF-MAA and not VBRI diagnosis, type 1 VWD was accurate in 105/110 (95.5%) samples. Bland-Altman analysis demonstrated good correlation between laboratory methods. VWD, types 2A, 2B, 1C VWD were also assigned by the VWF-MAA. CONCLUSIONS: We demonstrate that the VWF-MAA has utility in differentiating type 1 VWD, variant VWD and normal subjects in individuals undergoing an initial laboratory evaluation for bleeding.

Factors associated with the melanoma diagnostic interval in Ontario, Canada: a population-based study.

BACKGROUND: Protracted times to diagnosis of cancer can lead to increased patient anxiety, and in some cases, disease progression and worse outcomes. This study assessed the time to diagnosis for melanoma, and its variability, according to patient-, disease-, and system-level factors. METHODS: This is a descriptive, cross-sectional study in Ontario, Canada from 2007-2019. We used administrative health data to measure the diagnostic interval (DI)-and its two subintervals-the primary care subinterval (PCI) and specialist care subinterval (SCI). Multivariable quantile regression was used. RESULTS: There were 33,371 melanoma patients. The median DI was 36 days (interquartile range [IQR]: 8-85 days), median PCI 22 days (IQR: 6-54 days), and median SCI 6 days (IQR: 1-42 days). Increasing comorbidity was associated with increasing DI. Residents in the most deprived neighbourhoods and those in rural areas experienced shorter DIs and PCIs, but no differences in SCI. There was substantial variation in the DI and SCI across health regions, but limited differences in the PCI. Finally, patients with a history of non-melanoma skin cancer, and those previously established with a dermatologist experienced significantly longer DI, PCI, and SCI. DISCUSSION: This study found variability in the melanoma DI, notably by system-level factors.

Total hip arthroplasty for displaced femoral neck fracture: Survey of orthopaedic surgeons in Ontario, Canada.

BACKGROUND: Total hip arthroplasty (THA) for displaced femoral neck fractures in older patients remains a controversial topic. This study describes patient and surgeon factors that are associated with surgeons' recommendation of THA for this patient population. Furthermore, this study explores surgeon perceptions on why most patients are treated with hemiarthroplasty over THA. METHODS: In October 2019, a cross-sectional survey was mailed to practicing orthopaedic surgeons in Ontario, Canada. The questionnaire included paper patient cases to capture surgical practice variation using a full factorial, vignette-based experimental design. Multilevel linear regression and multivariable linear regression were used to determine patient and surgeon factors that are associated with treatment recommendations. RESULTS: Of a target population of 494 practicing surgeons, 302 (61.1%) responded. Sixty percent of respondents worked in the community, and most respondents (89.4%) had fellowship training. Surgeon-level predictors of treatment with THA included higher volume of THA for fracture in the last 12 months, having an elective THA practice, and increasing years in practice. Pre-existing hip arthritis increased likelihood to recommend THA, while increasing patient age and comorbidity burden decreased likelihood to recommend THA. There are medical, institutional, financial, and historic reasons why most patients are treated with hemiarthroplasty over THA. INTERPRETATION: This survey identified several patient and surgeon-level factors that were associated with treatment recommendation for THA. Hemiarthroplasty remains the more common treatment for this patient population for multiple reasons. There is potential for differential access to care when the factors driving treatment decisions are unrelated to the patient.

Comparative Effectiveness of Total Hip Arthroplasty and Hemiarthroplasty for Femoral Neck Fracture: A Propensity-Score-Matched Cohort Study.

BACKGROUND: The optimal treatment of older patients with a displaced femoral neck fracture remains a controversial topic. This study aimed to compare clinical outcomes across a matched group of patients with a femoral neck fracture treated with either hemiarthroplasty or total hip arthroplasty (THA). METHODS: Routinely collected health-care databases were linked to create a population-based cohort of 49,597 patients ≥60 years old from Ontario, Canada, who underwent hemiarthroplasty or THA for a femoral neck fracture between 2002 and 2017. A propensity-score-matched cohort was created using relevant and available predictors of treatment assignment and outcomes of interest. Clinical outcomes consisting of hip dislocation, revision surgery, hospital readmission, and death were compared in the matched cohort using survival analysis. RESULTS: Over 99% of THA patients (4,612) were adequately matched 1:1 to hemiarthroplasty patients (total matched cohort = 9,224). Patients treated with THA were at higher risk for hip dislocation at 30 days and 1 and 2 years postoperatively (2-year risk, 1.8% for THA versus 0.8% for hemiarthroplasty; p < 0.001). There was no difference in the short-term (30-day) or long-term (up to 10-year) risk of revision surgery between treatment groups. There was no significant difference in the risk of 30-day hospital readmission between groups. The risk of death at 1 year and 2 years postoperatively was lower for patients treated with THA. CONCLUSIONS: For patients with a hip fracture, shared decision-making should involve discussion of the potential higher risk of short-term hip dislocation after THA compared with hemiarthroplasty. The risk of revision surgery was similar between treatment groups at up to 10 years of follow-up. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Total hip arthroplasty versus hemiarthroplasty for treatment of femoral neck fractures : a population-based analysis of practice variation in Ontario, Canada.

AIMS: This study aimed to describe practice variation in the use of total hip arthroplasty (THA) for older patients with femoral neck fracture and to determine the association between patient, surgeon, and institution factors and treatment with THA. METHODS: We performed a cross-sectional analysis of 49,597 patients aged 60 years and older from Ontario, Canada, who underwent hemiarthroplasty or THA for femoral neck fracture between 2002 and 2017. This population-based study used routinely collected healthcare databases linked through ICES (formerly known as the Institute for Clinical Evaluative Sciences). Multilevel logistic regression modelling was used to quantify the association between patient, surgeon, and institution-level variables and whether patients were treated with THA. Variance partition coefficient and median odds ratios were used to estimate the variation attributable to higher-level variables and the magnitude of effect of higher-level variables, respectively. RESULTS: Over the study period, 9.4% of patients (n = 4,638) were treated with THA. Patient factors associated with higher likelihood of treatment by THA included: younger age, male sex, and diagnosis with rheumatoid arthritis. Long-term care residence, use of home care services prior to hip fracture, diagnosis of dementia, higher comorbidity burden, and the most marginalized group were negatively associated with treatment by THA. Treating surgeon and institution accounted for 54.2% and 17.8% of the total variation in treatment with THA, respectively. Surgeon volume of THA procedures in the 365 days prior to surgery was the strongest higher-level predictor of treatment with THA. Specific treating surgeons and institutions still accounted for significant proportions of the variability in treatment with THA (40.3% and 19.5% of total observed variation, respectively) after controlling for available patient, surgeon, and institution-level variables. CONCLUSION: The strongest predictors for treatment of patients with femoral neck fracture with THA were patient age, treating surgeon, and treating institution. This practice variation highlights differential access to care for patients.Cite this article: Bone Joint J 2023;105-B(2):180-189.

Factors Associated with the Breast Cancer Diagnostic Interval across Five Canadian Provinces: A CanIMPACT Retrospective Cohort Study.

The cancer diagnostic process can be protracted, and it is a time of great anxiety for patients. The objective of this study was to examine inter- and intra-provincial variation in diagnostic intervals and explore factors related to the variation. This was a multi-province retrospective cohort study using linked administrative health databases. All females with a diagnosis of histologically confirmed invasive breast cancer in British Columbia (2007-2010), Manitoba (2007-2011), Ontario (2007-2010), Nova Scotia (2007-2012), and Alberta (2004-2010) were included. The start of the diagnostic interval was determined using algorithms specific to whether the patient's cancer was detected through screening. We used multivariable quantile regression analyses to assess the association between demographic, clinical and healthcare utilization factors with the diagnostic interval outcome. We found significant inter- and intra-provincial variation in the breast cancer diagnostic interval and by screen-detection status; patients who presented symptomatically had longer intervals than screen-detected patients. Interprovincial diagnostic interval variation was 17 and 16 days for screen- and symptom-detected patients, respectively, at the median, and 14 and 41 days, respectively, at the 90th percentile. There was an association of longer diagnostic intervals with increasing comorbid disease in all provinces in non-screen-detected patients but not screen-detected. Longer intervals were observed across most provinces in screen-detected patients living in rural areas. Having a regular primary care provider was not associated with a shorter diagnostic interval. Our results highlight important findings regarding the length of the breast cancer diagnostic interval, its variation within and across provinces, and its association with comorbid disease and rurality. We conclude that diagnostic processes can be context specific, and more attention should be paid to developing tailored processes so that equitable access to a timely diagnosis can be achieved.

Psychometric Properties of the Coercion in Intimate Partner Relationships Scale.

Coercive control is defined as the systematic use of demands, threats, and surveillance behaviors to gain control over an individual. Content validity appears to be an issue for existing measures of coercive control tactics, as they do not assess all of these behaviors. This study investigated the validity and reliability of the Demand, Threat, Surveillance, and Response to Demands subscales of the Coercion in Intimate Partner Relationships (CIPR) scale. Participants (N = 541) completed online measures of coercive control, physical intimate partner violence, depression, and posttraumatic stress disorder symptomatology. Confirmatory factor analyses, linear regressions, and correlational analyses investigated the construct (i.e., concurrent, convergent, and discriminant) validity of the CIPR subscales. Internal consistency of the subscales and test-retest reliability were also examined. Results provided support for the validity and reliability of the CIPR. Implications and usage of the CIPR in research and practice are discussed. We report how we determined our sample size, all data exclusions, all manipulations, and all measures in the study.

Kinetics of isotropic to string-like phase switching in electrorheological fluids of nanocubes.

Applying an electric field to polarizable colloidal particles, whose permittivity differs from that of the dispersing medium, generates induced dipoles that promote the formation of string-like clusters and ultimately alter the fluid mechanical and rheological properties. Complex systems of this kind, whose electric-field-induced rheology can be manipulated between that of viscous and elastic materials, are referred to as electrorheological fluids. By using dynamic Monte Carlo simulations, we investigate the dynamics of self-assembly of dielectric nanocubes upon application of an electric field. Switching the field on induces in-particle dipoles and, at sufficiently large field intensity, leads to string-like clusters of variable length across a spectrum of volume fractions. The kinetics of switching from the isotropic to the string-like state suggests the existence of two mechanisms, the first related to the nucleation of chains and the second to the competition between further merging and separation. We characterize the transient unsteady state by following the chain length distribution and analyzing the probability of the transition of nanocubes from one chain to another over time. Additionally, we employ passive microrheology to gain insight into the effect of the electric field on the viscoelastic response of our model fluid. Not only do we observe that it becomes more viscoelastic in the presence of the field but also that its viscoelasticity assumes an anisotropic signature, with both viscous and elastic moduli in planes perpendicular to the external field being larger than those along it.

Explaining regional variations in colon cancer survival in Ontario, Canada: a population-based retrospective cohort study.

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.

Time to Surgery for Patients with Esophageal Cancer Undergoing Trimodal Therapy in Ontario: A Population-Based Cross-Sectional Study.

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.

A population-based validation study of the 8th edition UICC/AJCC TNM staging system for cutaneous melanoma.

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.

Regional variations and associations between colonoscopy resource availability and colonoscopy utilisation: a population-based descriptive study in Ontario, Canada.

OBJECTIVE: There is substantial variation in colonoscopy use and evidence of long wait times for the procedure. Understanding the role of system-level resources in colonoscopy utilisation may point to a potential intervention target to improve colonoscopy use. This study characterises colonoscopy resource availability in Ontario, Canada and evaluates its relationship with colonoscopy utilisation. DESIGN: We conducted a population-based study using administrative health data to describe regional variation in colonoscopy availability for Ontario residents (age 18-99) in 2013. We identified 43 colonoscopy networks in the province in which we described variations across three colonoscopy availability measures: colonoscopist density, private clinic access and distance to colonoscopy. We evaluated associations between colonoscopy resource availability and colonoscopy utilisation rates using Pearson correlation and log binomial regression, adjusting for age and sex. RESULTS: There were 9.4 full-time equivalent colonoscopists per 100 000 Ontario residents (range across 43 networks 0.0 to 21.8); 29.5% of colonoscopies performed in the province were done in private clinics (range 1.2%-55.9%). The median distance to colonoscopy was 3.7 km, with 5.9% travelling at least 50 km. Lower colonoscopist density was correlated with lower colonoscopy utilisation rates (r=0.53, p<0.001). Colonoscopy utilisation rates were 4% lower in individuals travelling 50 to <200 km and 11% lower in individuals travelling ≥200 km to colonoscopy, compared to <10 km. There was no association between private clinic access and colonoscopy utilisation. CONCLUSION: The substantial variations in colonoscopy resource availability and the relationship demonstrated between colonoscopy resource availability and use provides impetus for health service planners and decision-makers to address these potential inequalities in access in order to support the use of this medically necessary procedure.

Multiple Sclerosis and the Cancer Diagnosis: Diagnostic Route, Cancer Stage, and the Diagnostic Interval in Breast and Colorectal Cancer.

BACKGROUND AND OBJECTIVES: The multiple sclerosis (MS) population's survival from breast cancer and colorectal cancer is compromised. Cancer screening and timely diagnoses affect cancer survival and have not been studied in the MS cancer population. We investigated whether the diagnostic route, cancer stage, or diagnostic interval differed in patients with cancer with and without MS. METHODS: We conducted a matched population-based cross-sectional study of breast cancers (2007-2015) and colorectal cancers (2009-2012) in patients with MS from Ontario, Canada, using administrative data. Exclusion criteria included second or concurrent primary cancers, no health care coverage, and, for the patients without MS, those with any demyelinating disease. We based 1:4 matching of MS to non-MS on birth year, sex (colorectal only), postal code, and cancer diagnosis year (breast only). Cancer outcomes were diagnostic route (screen-detected vs symptomatic), stage (stage I vs all others), and diagnostic interval (time from first presentation to diagnosis). Multivariable regression analyses controlled for age, sex (colorectal only), diagnosis year, income quintile, urban/rural residence, and comorbidity. RESULTS: We included 351 patients with MS and breast cancer, 1,404 matched patients with breast cancer without MS, 54 patients with MS and colorectal cancer, and 216 matched patients with colorectal cancer without MS. MS was associated with fewer screen-detected cancers in breast (odds ratio [OR] 0.68 [95% CI 0.52, 0.88]) and possibly colorectal (0.52 [0.21, 1.28]) cancer. MS was not associated with differences in breast cancer stage at diagnosis (stage I cancer, OR 0.81 [0.64, 1.04]). MS was associated with greater odds of stage I colorectal cancer (OR 2.11 [1.03, 4.30]). The median length of the diagnostic interval did not vary between people with and without MS in either the breast or colorectal cancer cohorts. Controlling for disability status attenuated some findings. DISCUSSION: Breast cancers were less likely to be detected through screening and colorectal cancer more likely to be detected at early stage in people with MS than without MS. MS-related disability may prevent people from getting mammograms and colonoscopies. Understanding the pathways to earlier detection in both cancers is critical to developing and planning interventions to ameliorate outcomes for people with MS and cancer.

Real-world colorectal cancer diagnostic pathways in Ontario, Canada: A population-based study.

OBJECTIVE: This study aimed to identify colorectal cancer (CRC) diagnostic pathways and describe patients in those pathway groups. METHODS: This was a cross-sectional study of CRC patients in Ontario, Canada, diagnosed 2009-2012 that used linked administrative data at ICES. We used cluster analysis on 11 pathway variables characterising patient presentation, symptoms, procedures and referrals. We assessed associations between patient- and disease-related characteristics and diagnostic pathway group. We further characterised the pathways by diagnostic interval and number of related physician visits. RESULTS: Six diagnostic pathways were identified, with three adhering to provincial diagnostic guidelines: screening (N = 4494), colonoscopy (N = 10,066) and imaging plus colonoscopy (N = 3427). Non-adherent pathways were imaging alone (N = 2238), imaging and emergency presentation (N = 2849) and no pre-diagnostic workup (N = 887). Patients in adherent pathways were younger, had fewer comorbidities, lived in less deprived areas and had earlier stage disease. The median diagnostic interval length varied across pathways from 12 to 126 days, correlating with the number of CRC-related visits. CONCLUSIONS: This study demonstrated substantial variations in real-world CRC diagnostic pathways and 25% were diagnosed through non-adherent pathways. Those patients were older, had more comorbid disease and had higher stage cancer. Further research needs to identify and describe the reasons for divergent diagnostic processes.

Time to treatment of esophageal cancer in Ontario: A population-level cross-sectional study.

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 < .0001), greater comorbidity (P = .0005), greater material deprivation (P = .001), rurality (P = .03), histology (P = .02), and treatment group (P < .0001) were associated with a longer median TI. Older age (P = .03), greater comorbidity (P = .003), greater material deprivation (P = .005), rurality (P = .04), and treatment group (P < .0001) were associated with a longer 90th percentile TI. Conclusions: Geographic variability of time to treatment exists across Ontario. Investigation of facility-level differences is warranted. Patient and disease factors are associated with longer wait times. These results might inform future health care policy and resource allocation.

Predictors of Postoperative Liver Decompensation Events After Resection in Patients with Cirrhosis and Hepatocellular Carcinoma: A Population-Based Study.

BACKGROUND: Appropriate patient selection for liver resection in hepatocellular carcinoma (HCC) is critical to mitigation of major liver-related postoperative complications. Currently, no standard prognostic tool exists to predict the risk of postoperative liver decompensation events (POLDEs) after partial hepatectomy for patients with cirrhosis and HCC. This study aimed to identify independent preoperative predictors of POLDEs for future development of prognostic tools to improve surgical decision-making. METHODS: This population-based, retrospective cohort study investigated patients with cirrhosis and incident HCC between 2007 and 2017, identified using administrative health data from Ontario, Canada. The occurrence of a POLDE or death within 2 years after surgery was described. Multivariable Cox regression identified independent predictors of POLDE-free survival, as well as cause-specific hazards for POLDEs and death. RESULTS: Among 611 patients with cirrhosis and HCC who underwent liver resection, 160 (26.2%) experienced at least one POLDE, and 189 (30.9%) died within 2 years after surgery. Diabetes, cirrhosis etiology, major liver resection, and previous non-malignant decompensation were independent predictors of POLDE-free survival. Except for extent of resection, the same risk factors were associated with POLDEs in the cause-specific analysis. In contrast, only age and history of previous non-malignant decompensation were independent predictors of mortality. CONCLUSIONS: Among patients with cirrhosis undergoing resection for HCC, patient and disease-related factors are associated with POLDEs and POLDE-free survival. These factors can be used both to inform clinical practice and to advance the development of preoperative prognostic tools, which may lead to improved outcomes for this population.

A host-directed macrocyclic peptide therapeutic for MDR gram negative bacterial infections.

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.

Appraisal of multivariable prognostic models for post-operative liver decompensation following partial hepatectomy: a systematic review.

BACKGROUND: Few reports have evaluated prognostic modelling studies of tools used for surgical decision-making. This systematic review aimed to describe and critically appraise studies that have developed or validated multivariable prognostic models for post-operative liver decompensation following partial hepatectomy. METHODS: This study was designed using the CHARMS checklist. Following a comprehensive literature search, two reviewers independently screened candidate references for inclusion and abstracted relevant study details. Qualitative assessment was performed using the PROBAST tool. RESULTS: We identified 36 prognostic modelling studies; 25 focused on development only, 3 developed and validated models, and 8 validated pre-existing models. None compared routine use of a prognostic model against standard clinical practice. Most studies used single-institution, retrospective cohort designs, conducted in Eastern populations. In total, 15 different outcome definitions for post-operative liver decompensation events were used. Statistical concerns surrounding model overfitting, performance assessment, and internal validation led to high risk of bias for all studies. CONCLUSIONS: Current prognostic models for post-operative liver decompensation following partial hepatectomy may not be valid for routine clinical use due to design and methodologic concerns. Landmark resources and reporting guidelines such as the TRIPOD statement may assist researchers, and additionally, model impact assessment studies represent opportunities for future research.