Impact of diabetes on colorectal cancer stage and mortality risk: a population-based cohort study.

AIMS/HYPOTHESIS: Diabetes is associated with an increased incidence of colorectal cancer (CRC). There exists conflicting evidence regarding the impact of diabetes on CRC-specific mortality (herein also referred to as cancer-specific mortality). The objectives of this study were to determine whether diabetes is associated with a more advanced CRC stage at diagnosis and with higher all-cause and cancer-specific mortality. METHODS: This retrospective cohort study used linked, population-based health databases from Ontario, Canada. Among individuals diagnosed with CRC from 2007 to 2015, we compared the likelihood of presenting with later- (III or IV) vs early- (I or II) stage CRC between patients with and without diabetes adjusting for relevant covariates. We then determined the association between diabetes and all-cause and CRC-specific mortality, after adjusting for CRC stage at diagnosis and other covariates. RESULTS: Of the 44,178 individuals with CRC, 11,822 (26.7%) had diabetes. After adjustment for CRC screening and other covariates, individuals with diabetes were not more likely to present with later-stage CRC (adjusted OR 0.97, 95% CI 0.93, 1.01). Over a median follow-up of 2.63 (interquartile range [IQR] 0.97-5.10) years, diabetes was associated with higher all-cause mortality (adjusted HR 1.08, 95% CI 1.04, 1.12) but similar cancer-specific survival (adjusted HR 1.0, 95% CI 0.95, 1.06). CONCLUSIONS/INTERPRETATION: Individuals with diabetes who develop CRC are not more likely to present with a later stage of CRC and have similar cancer-specific mortality compared with those without diabetes. Diabetes was associated with higher all-cause mortality in CRC patients, indicating that greater attention to non-cancer care is needed for CRC survivors with diabetes.

Variations in RBC and frozen plasma utilization rates across 62 Ontario community hospitals.

BACKGROUND: Recent province-wide audits of frozen plasma (FP) and RBC use in Ontario showed a high rate of inappropriate transfusions. STUDY DESIGN AND METHODS: This was a retrospective, ecological study to determine variations in RBC and FP utilization rates across Ontario community hospitals between 2012 and 2017. Annual utilization rates were reported using descriptive statistics. Rates of blood component use were correlated with size of hospital, presence of specialized programs, and quality improvement (QI) initiatives, using Poisson regression. RESULTS: RBC and FP utilization rates decreased from 2012 to 2017 (p = 0.03 for FP; p < 0.01 for RBC). There was a 10-fold difference in RBC and FP transfusion rates between the highest and lowest users. Smaller hospitals (p < 0.05) and sites with any QI initiative (p = 0.006) were associated with lower FP utilization rates. Hospitals without cancer programs (p = 0.02) and sites with RBC guidelines (p = 0.05) or with technologists who prospectively screened transfusion orders (p = 0.01) had lower RBC transfusion rates. RBC utilization rates decreased further after the implementation of RBC guidelines (p = 0.02) and order sets (p = 0.005). There was a positive correlation between FP and RBC transfusion rates for each fiscal year (p < 0.005 for all years). CONCLUSION: RBC and FP utilization showed wide variation across community hospitals in Ontario. Overall, transfusion rates decreased over time. A further decrease was observed at sites with QI initiatives, supporting their implementation in reducing utilization. These data will serve as a baseline to highlight sites and practices where QI initiatives may be most beneficial and replicated in other jurisdictions.

Survival rates of biological therapies for psoriasis treatment in real-world clinical practice: A Canadian multicentre retrospective study.

BACKGROUND/OBJECTIVES: Data on biologic drug survival in real-world psoriasis treatment are limited. There is a need to evaluate long-term trends of biologic use outside the realm of clinical trials. METHODS: A multicentre chart review was conducted with patients' data from September 2005 to September 2014. Kaplan-Meier plot analysis was used to determine 5-year drug survival rates. A log-rank test was used to compare the rates of drug survival between the studied biologics. RESULTS: For the 398 patients and 545 treatment series analysed, 1, 2, 3, 4 and 5-year survival rates were 0.826, 0.687, 0.563, 0.475 and 0.420 with etanercept; 0.804, 0.648, 0.553, 0.508 and 0.508 with adalimumab; 0.838, 0.664, 0.554, 0.485 and 0.382 with infliximab; and 0.914, 0.856, 0.800, 0.755 and 0.755 with ustekinumab, respectively. A statistically significant difference was seen between ustekinumab and the other three biologics. CONCLUSION: A progressive decrease in treatment adherence was seen with all four biologics, as expected, but the survival rate of ustekinumab was highest.

Rates and Predictors of Endoscopic and Clinical Recurrence After Primary Ileocolic Resection for Crohn's Disease.

BACKGROUND AND AIMS: The utility of postoperative medical prophylaxis (POMP) and the treatment of mild endoscopic recurrence remain controversial. METHODS: This study is a retrospective review of patients undergoing a primary ileocolic resection for CD at a single academic center. Endoscopic recurrence (ER) was defined using the Rutgeerts score (RS), and clinical recurrence (CR) was defined as symptoms of CD with endoscopic or radiologic evidence of neo-terminal ileal disease. RESULTS: There were 171 patients who met inclusion criteria. The cumulative probability of ER (RS ≥ i-1) at 1, 2, and 5 years was 29, 51, and 77 %, respectively. The only independent predictors of ER were the absence of POMP (HR 1.50; P = 0.03) and penetrating disease behavior (HR 1.50; P = 0.05). The cumulative probability of CR at 1, 2, and 5 years was 8, 13, and 27 %, respectively. There was a higher rate of clinical recurrence in patients with RS-2 compared to RS-1 on the initial postoperative endoscopy (HR 2.50; P = 0.02). In 11 patients not exposed to POMP with i-1 on initial endoscopy, only 2 patients (18 %) progressed endoscopically during the study period while 5 patients (45 %) regressed to i-0 on subsequent endoscopy without treatment. CONCLUSIONS: Postoperative medical prophylaxis decreased the likelihood of ER while certain phenotypes of CD appear to increase the risk of developing ER and CR. There may be a role for watchful waiting in patients with mild endoscopic recurrence on the initial postoperative endoscopy.

Risk of Malignancy in Dermatomyositis and Polymyositis.

BACKGROUND: There is variation in the risk of malignancy in dermatomyositis (DM) and polymyositis (PM) in the existing literature. OBJECTIVE: To conduct a meta-analysis to estimate the risk of malignancy in DM and PM as compared with the general population. METHODS: Medline and Embase Database abstracts were searched through August 2014 using the search terms myositis, neoplasms, and paraneoplastic syndromes. Population-based, observational studies in English were included. Meta-analyses were conducted using random-effects models. RESULTS: A total of 5 studies with 4538 DM or PM patients were included in the analysis. The overall relative risk was 4.66 for DM and 1.75 for PM. By gender, the standardized incidence ratio (SIR) of malignancy among DM patients was 5.29 for males and 4.56 for females; the SIR of malignancy among PM patients was 1.62 for males and 2.02 for females. By time since diagnosis, the SIR of malignancy among DM patients was 17.29 in the first year, 2.7 between 1 and 5 years, and 1.37 after 5 years. By age group, the SIR among DM patients was 2.79 for patients between 15 and 44 years and 3.13 beyond 45 years. CONCLUSIONS: Both DM and PM are associated with increased risk of malignancy, but the risk is higher in DM. The risk of malignancy is present in both genders and all age groups and is highest in the first year after diagnosis but persists beyond the fifth year in DM. Adults should be evaluated for malignancy at diagnosis, followed by long-term surveillance.

MACEs Not Associated With the Use of Biologic Therapy for Psoriasis in Real-World Clinical Practice: A Canadian Multicenter Retrospective Study.

INTRODUCTION: Previous reports have shown inconsistent findings with regard to the relationship between biologic therapy and risk for major adverse cardiovascular events (MACEs). OBJECTIVES: The aim of this study was to determine the overall rate of MACEs in a cohort of 398 patients. METHODS: All patients treated with biologics for psoriasis at 2 academic centers in Toronto, Ontario, between September 2005 and September 2014 were considered for inclusion. Medical records were reviewed to identify MACEs. RESULTS: A total of 398 patients were included. The median duration of disease was 19.8 years. Median time to biologic therapy withdrawal because of an adverse event was 23.5 months. In this cohort, no MACEs were identified in patients treated with biologic therapy. CONCLUSIONS: Biologic treatment for psoriasis was not associated with increased cardiovascular risk in this cohort. These results require validation in larger studies.

Adverse events resulting in withdrawal of biologic therapy for psoriasis in real-world clinical practice: A Canadian multicenter retrospective study.

BACKGROUND: Safety profiles of biologics for treatment of psoriasis are limited to data from randomized controlled trials. There is a need for comparative safety reports of biologics based on data from clinical practice. OBJECTIVE: We sought to estimate and compare the incidence of adverse events (AEs) leading to withdrawal of biologics (etanercept, infliximab, adalimumab, and ustekinumab) in the treatment of psoriasis. METHODS: We conducted a multicenter retrospective chart review from September 2005 to September 2014. Incidence proportion and rate of AEs leading to withdrawal by biologic agent and AE were calculated. RESULTS: For 545 treatments administered in 398 patients, 22 (4.04%) AEs were associated with withdrawal, for a rate of 1.97/100 patient-years (95% confidence interval [CI] 1.32-2.94). Common AEs were injection-/infusion-site reactions (0.55%, 0.92%, 0%, and 0% for etanercept, infliximab, adalimumab, and ustekinumab, respectively); infections (0%, 0.18%, 0.55%, 0.18%); and malignancies (0.18%, 0.18%, 0%, 0.37%). LIMITATIONS: Possible incompleteness of chart details and small study population limit the conclusiveness of findings. CONCLUSION: Biologic agents for treatment of psoriasis are safe; AEs associated with withdrawal occurred in 4% of all administered biologic therapies. It does not appear that real-world patients encounter more AEs with biologics than patients in clinical trials.

Plasma apolipoprotein A1 as a biomarker for Parkinson disease.

OBJECTIVE: To identify plasma-based biomarkers for Parkinson disease (PD) risk. METHODS: In a discovery cohort of 152 PD patients, plasma levels of 96 proteins were measured by multiplex immunoassay; proteins associated with age at PD onset were identified by linear regression. Findings from discovery screening were then assessed in a second cohort of 187 PD patients, using a different technique. Finally, in a third cohort of at-risk, asymptomatic individuals enrolled in the Parkinson's Associated Risk Study (PARS, n = 134), plasma levels of the top candidate biomarker were measured, and dopamine transporter (DAT) imaging was performed, to evaluate the association of plasma protein levels with dopaminergic system integrity. RESULTS: One of the best candidate protein biomarkers to emerge from discovery screening was apolipoprotein A1 (ApoA1; p = 0.001). Low levels of ApoA1 correlated with earlier PD onset, with a 26% decrease in risk of developing PD associated with each tertile increase in ApoA1 (Cox proportional hazards, p < 0.001, hazard ratio = 0.742). The association between plasma ApoA1 levels and age at PD onset was replicated in an independent cohort of PD patients (p < 0.001). Finally, in the PARS cohort of high-risk, asymptomatic subjects, lower plasma levels of ApoA1 were associated with greater putaminal DAT deficit (p = 0.037). INTERPRETATION: Lower ApoA1 levels correlate with dopaminergic system vulnerability in symptomatic PD patients and in asymptomatic individuals with physiological reductions in dopamine transporter density consistent with prodromal PD. Plasma ApoA1 may be a new biomarker for PD risk.

Risk of Adverse Cardiovascular Outcomes in Differentiated Thyroid Cancer Survivors: A Systematic Review and Meta-Analysis.

Introduction: Long-term cardiovascular (CV) risk is a concern for differentiated thyroid cancer (DTC) survivors. Methods: We performed a systematic review and meta-analysis evaluating the risks of CV mortality and morbidity in DTC survivors compared with the general population. Respective meta-analyses were conducted for data that were adjusted for relevant confounders and crude data. We searched five electronic databases from inception to October 2021, supplemented with a hand search. Two reviewers independently screened citations, reviewed full text articles, extracted data, and critically appraised the studies, with discrepancies resolved by a third reviewer. The primary outcome was CV mortality. Secondary outcomes included atrial fibrillation, ischemic heart disease, stroke, and heart failure. We estimated the relative risk (RR) and confidence intervals [CI] of outcomes using random-effects models (adjusted for age and gender), compared with the general population. Results: We reviewed 3409 unique citations, 65 full text articles, and included 7 studies. CV mortality risk was significantly increased in DTC survivors in one study adjusted for confounders-adjusted RR (aRR) 3.35 ([CI 1.66-6.67]; 524 DTC, 1572 controls). The risk of CV morbidity in DTC survivors, adjusted for risk factors, was estimated as follows: atrial fibrillation-aRR 1.66 [CI 1.22-2.27] (3 studies, 4428 DTC, I2 = 75%), ischemic heart disease-aRR 0.97 [CI 0.84-1.13] (2 studies, 3910 DTC, I2 = 0%), stroke-aRR 1.14 [CI 0.84-1.55] (2 studies, 3910 DTC, I2 = 69%), and heart failure-aRR 0.98 [CI 0.60-1.59] (2 studies, 3910 DTC, I2 = 79%). In meta-analyses of unadjusted data, the risks of CV mortality were not significantly increased but the CV morbidity risks were similar to adjusted data. Conclusions: There is limited evidence suggesting that DTC survivors may be at an increased risk of CV death and atrial fibrillation (after adjustment for confounders). We did not observe a significantly increased risk of ischemic heart disease, stroke, or heart failure. Most analyses were subject to significant heterogeneity and further research, with careful attention to CV risk factors, is needed to clarify CV risk in DTC survivors. Registration: PROSPERO CRD42021244743.

Gaps in Referral to Bariatric Surgery for Patients With Type 2 Diabetes Seen in Endocrinology Clinics.

OBJECTIVES: One-third of adults in Canada are overweight and 26.8% experience obesity. Bariatric surgery confers effective weight loss and reduces obesity-related complications, including type 2 diabetes, but remains an underutilized treatment. Our objective in this study was to determine whether a gap exists in bariatric program referrals for patients with type 2 diabetes seen in endocrinology clinics at an ambulatory tertiary care hospital in Toronto, Canada. METHODS: A retrospective chart review was conducted of 843 consecutive patients with type 2 diabetes in endocrinology clinics between January 1, 2015 and December 31, 2020. Inclusion criteria were age ≥18 years, type 2 diabetes and body mass index (BMI)>35 kg/m2. Exclusion criteria were recent active cancer, uncontrolled psychiatric disease or active substance use disorder within 6 months of the initial visit. Referrals to bariatric surgery were assessed within a 5-year follow-up period and compared with baseline referral rates from the Ontario Bariatric Network (OBN). An online survey of 48 endocrinologists in Toronto, Ontario, was also conducted to assess physician-level barriers to referral. RESULTS: The proportion of patients with class II obesity (BMI>35 kg/m2) and type 2 diabetes meeting the eligibility criteria for bariatric referral was 4.6% (n=38). A documented discussion about bariatric surgery occurred with 7 (18.0%) of these eligible patients, and 1 patient (2.6%) was referred for surgery. Aside from surgical referrals, only 2.6% of eligible patients were referred to cognitive-behavioural therapy, 36.8% were initiated on obesity pharmacotherapy and 42.1% were referred to a dietitian. Baseline OBN data demonstrated that most surgical referrals (n=6,360) were from family physicians (65.0%) and only 8.8% were from a medical specialist. Eight percent of surveyed endocrinologists reported that they discussed bariatric surgery with at least half of their eligible patients. The most frequent barrier to discussing bariatric surgery during visits was time constraints. Physicians identified that simplifying the referral process and providing bariatric surgery handouts would be helpful interventions to improve referral rates. CONCLUSIONS: Our gap analysis demonstrated a low bariatric surgery referral rate by tertiary care endocrinologists. Our study also identified a large gap in the appropriate treatment of obesity with poor utilization of behavioural, lifestyle and pharmacotherapy practices. As obesity and diabetes rates increase, better education, training and knowledge translation will be necessary to overcome weight bias and prioritize obesity management.

Association between diabetes, obesity, aging, and cancer: review of recent literature.

Rates of obesity and diabetes have risen significantly in recent years and are projected to increase even further in the coming decades. Obesity and diabetes are associated with increased risk of certain tumours, with the strongest relationships demonstrated for colorectal, post-menopausal breast, and endometrial cancer. Another important risk factor for cancer development is aging. Aging is characterized by chronic inflammation and immunosenescence, and accelerated by obesity, which may further stimulate the development of cancer. In this review, we summarize recent literature on the complex interactions between obesity, diabetes, aging, and cancer risk and mortality. We will also provide an overview of both epidemiological as well as pathophysiologic data and their clinical implications. In the context of an aging population and anticipated rise in rates of obesity and diabetes, a better understanding of how these factors interact and impact on cancer risk and prognosis will be important in helping to guide therapeutic interventions.

Support systems of women with epilepsy in pregnancy: A retrospective needs assessment.

PURPOSE: To explore support systems for women with epilepsy (WWE) during pregnancy. METHODS: Audio-recorded, transcribed, semi-structured telephone interviews with WWE in pregnancy and following childbirth were coded using descriptive thematic analysis. RESULTS: Twelve women with epilepsy aged 21-37 years who received care during pregnancy in our epilepsy clinic from 2010 to 2013 were interviewed. Women identified three areas of support: immediate family, their specialist and group support. Some women felt unable to fully share health concerns with family members, but appreciated their support. Neurologists were perceived as reliable sources of support and information, but could be inaccessible. Support groups were seen as beneficial, but may heighten women's fear of epilepsy-related adverse events during pregnancy. CONCLUSION: This study highlights the use of support systems by WWE during pregnancy. The richness of the transcribed interviews provides valuable insight into the pregnancy-experience of WWE and helps to direct future clinical and research goals and hypotheses.

Incidence, Risk Factors, and Surgical Management of Boston Type 1 Keratoprothesis Corneal Melts, Leaks, and Extrusions.

PURPOSE: To determine the rate of Boston type 1 keratoprosthesis (Kpro)-related corneal melts, leaks, and extrusions requiring surgical repair and to analyze possible risk factors and visual outcomes. METHODS: Retrospective chart review of 110 patients (128 eyes) who received a Kpro between November 2004 and December 2010 (average follow-up of 29 mo). The rate of corneal complications, risk factors for melts, and postmelt repair visual outcomes were evaluated. RESULTS: Twenty eyes from 18 patients developed Kpro-related melts requiring surgical repair. The incidence of melt-related complications was 16%. In total, there were 33 episodes of melt-related complications. Surgical repair included lamellar patch grafts (15), Kpro removal with penetrating keratoplasty (7), reassembly of Kpro onto a new cornea (4), replacement of Kpro (3), suturing of a leak (3), and enucleation (1). The majority of eyes (18/20) did not regain their best post-Kpro vision at final follow-up (average 10 mo and range, 1-36 mo after melt repair). Significant risk factors for melt included previous infectious keratitis [P < 0.0001, odds ratio (OR) = 12.50, 95% confidence interval (CI), 4.02-38.9] and conjunctival deficiency (ie, a diagnosis of Stevens-Johnson syndrome, mucous membrane pemphigoid, or chemical injury, P = 0.043, OR = 2.66, CI, 1.01-7.02). CONCLUSIONS: Patients who undergo Kpro with severe ocular surface disease are at greater risk for corneal melts, leaks, and extrusions. Patients with infectious keratitis and conjunctival deficiency are at an increased risk of developing corneal melts. Visual outcomes are poor after surgical repair of these complications.

Telemedicine in Parkinson's disease: A patient perspective at a tertiary care centre.

INTRODUCTION: To overcome travel distance and lack of local expertise, telemedicine programs have been implemented and are still pilot programs in many jurisdictions. Patient perspectives remain poorly understood. In the largest study to date, we examined user satisfaction and predictors of patient choice to use telemedicine among Parkinson's Disease (PD) patients in the context of a well-developed telemedicine system. These data can help to optimize healthcare delivery by telemedicine. METHODS: A patient satisfaction questionnaire was administered to current or previous users via telephone. Patients' cost savings were determined. The proportion of non-users interested in using telemedicine was quantified. Demographic and clinical characteristics of those who expressed interest in the program vs. those who did not were compared. RESULTS: A total of 34 users and 103 non-users were recruited. Users reported an average cost reduction of $200 and 209 minutes of reduction in commute time (p < 0.01). While a majority (29/34 users) reported interest in continuing with telemedicine, inexperience of some telehealth nurses was a major source of patient dissatisfaction. Patients preferred a combination of telehealth and in-person visits. A majority of non-users (55/103, 53%) declared interest in telemedicine, but it had not been offered to them. A lower Hoehn and Yahr stage and a longer commute time were associated with patient interest in telemedicine. CONCLUSIONS: Training of nurses is an important determinant of patient satisfaction. Clinicians should consider offering telehealth to all patients for whom it is medically appropriate, especially those who experience long travel times.

Clinical and biochemical differences in patients having Parkinson disease with vs without GBA mutations.

IMPORTANCE: Biochemical abnormalities present in GBA (mut/wt) carriers may offer new pathogenetic insights to and potential therapeutic targets in Parkinson disease (PD). OBJECTIVE: To determine whether patients having PD with vs without GBA mutations differ in clinical phenotype or plasma protein expression. DESIGN AND SETTING: Case-control study of patients having PD with vs without GBA mutations. Clinical characteristics were compared between groups, and biochemical profiling of 40 plasma proteins was performed to identify proteins that differed in expression between groups. PARTICIPANTS: The discovery cohort included 20 patients having PD with GBA mutations. Clinical characteristics of GBA-associated PD cases were compared with those of 242 patients having PD in whom GBA mutations were excluded by full gene sequencing. MAIN OUTCOME MEASURES: Biochemical profiling was available for all 20 GBA-associated PD cases, as well as a subset (87 of 242) of the GBA-negative PD cases. The replication cohort included 19 patients having PD with GBA mutations and 41 patients having PD without GBA mutations. RESULTS: Compared with patients having PD without GBA mutations, patients having PD with GBA mutations were younger at disease onset (P = .04) and were more likely to demonstrate cognitive dysfunction (P = .001). In a multiple regression model that included age, sex, and assay batch as covariates, GBA mutation status was significantly associated with plasma levels of interleukin 8 (P = .001), monocyte chemotactic protein 1 (P = .008), and macrophage inflammatory protein 1α (P = .005). The association between interleukin 8 and GBA mutation status was replicated (P = .03) in a separate cohort of patients having PD with vs without GBA mutations. CONCLUSIONS AND RELEVANCE: Patients having PD with GBA mutations have earlier age at disease onset and are more likely to demonstrate cognitive dysfunction. Monocyte-associated inflammatory mediators may be elevated in patients having PD with GBA mutations.

Effects of diurnal variation on the Test of Variables of Attention performance in young adults with attention-deficit/hyperactivity disorder.

The Test of Variables of Attention (TOVA) is a continuous performance test that assesses attention, impulsivity, and processing speed. Continuous performance tests are used in the assessment of attention-deficit/hyperactivity disorder (ADHD) in children and adults. TOVA norms are based on a morning administration, and any TOVA administered after 1:00 p.m. is flagged as potentially invalid. Whereas the testing time recommendations make sense for pediatric samples, it is unclear whether they are appropriate for young adults, who typically show significant phase delay in their diurnal rhythms. The current study explores the impact of time of day on TOVA performance in young adults with ADHD. Participants were randomly assigned to either morning or afternoon administration. We found no significant diurnal variation in TOVA performance. We also found no interaction between diurnal preference and time of day of administration. Night owls endorsed more inattention symptoms on a self-report measure than more intermediate individuals but actually made significantly fewer omission (inattention) errors on the TOVA. Self-reported symptoms of inattention showed moderate, significant correlations with various TOVA performance indices. Self-reported symptoms of hyperactivity and impulsivity, however, showed no relationship to TOVA performance. These results suggest that the TOVA can be administered to adults with ADHD outside of the hours recommended in the manual without significantly compromising the interpretative validity of test score interpretation. Thus, a TOVA report that is consistent with ADHD should not be dismissed simply because it was administered in the late afternoon.