Chronic disease prevention and screening outcomes for patients with and without financial difficulty: a secondary analysis of the BETTER WISE cluster randomised controlled trial.

OBJECTIVE: Building on Existing Tools To improvE chronic disease pRevention and screening in primary care Wellness of cancer survIvorS and patiEnts (BETTER WISE) was designed to assess the effectiveness of a cancer and chronic disease prevention and screening (CCDPS) programme. Here, we compare outcomes in participants living with and without financial difficulty. DESIGN: Secondary analysis of a cluster-randomised controlled trial. SETTING: Patients of 59 physicians from 13 clinics enrolled between September 2018 and August 2019. PARTICIPANTS: 596 of 1005 trial participants who responded to a financial difficulty screening question at enrolment. INTERVENTION: 1-hour CCDPS visit versus usual care. OUTCOME MEASURES: Eligibility for a possible 24 CCDPS actions was assessed at baseline and the primary outcome was the percentage of eligible items that were completed at 12-month follow-up. We also compared the change in response to the financial difficulty screening question between baseline and follow-up. RESULTS: 55 of 265 participants (20.7%) in the control group and 69 of 331 participants (20.8%) in the intervention group reported living with financial difficulty. The primary outcome was 29% (95% CI 26% to 33%) for intervention and 23% (95% CI 21% to 26%) for control participants without financial difficulty (p=0.01). Intervention and control participants with financial difficulty scored 28% (95% CI 24% to 32%) and 32% (95% CI 27% to 38%), respectively (p=0.14). In participants who responded to the financial difficulty question at both time points (n=302), there was a net decrease in the percentage of participants who reported financial difficulty between baseline (21%) and follow-up (12%, p<0.001) which was similar in the control and intervention groups. The response rate to this question was only 51% at follow-up. CONCLUSION: The BETTER intervention improved uptake of CCDPS manoeuvres in participants without financial difficulty, but not in those living with financial difficulty. Improving CCDPS for people living with financial difficulty may require a different clinical approach or that social determinants be addressed concurrently with clinical and lifestyle needs or both. TRIAL REGISTRATION NUMBER: ISRCTN21333761.

Socioeconomic Status, Palliative Care, and Death at Home Among Patients With Cancer Before and During COVID-19.

Importance: The COVID-19 pandemic had a profound impact on the delivery of cancer care, but less is known about its association with place of death and delivery of specialized palliative care (SPC) and potential disparities in these outcomes. Objective: To evaluate the association of the COVID-19 pandemic with death at home and SPC delivery at the end of life and to examine whether disparities in socioeconomic status exist for these outcomes. Design, Setting, and Participants: In this cohort study, an interrupted time series analysis was conducted using Ontario Cancer Registry data comprising adult patients aged 18 years or older who died with cancer between the pre-COVID-19 (March 16, 2015, to March 15, 2020) and COVID-19 (March 16, 2020, to March 15, 2021) periods. The data analysis was performed between March and November 2023. Exposure: COVID-19-related hospital restrictions starting March 16, 2020. Main Outcomes and Measures: Outcomes were death at home and SPC delivery at the end of life (last 30 days before death). Socioeconomic status was measured using Ontario Marginalization Index area-based material deprivation quintiles, with quintile 1 (Q1) indicating the least deprivation; Q3, intermediate deprivation; and Q5, the most deprivation. Segmented linear regression was used to estimate monthly trends in outcomes before, at the start of, and in the first year of the COVID-19 pandemic. Results: Of 173 915 patients in the study cohort (mean [SD] age, 72.1 [12.5] years; males, 54.1% [95% CI, 53.8%-54.3%]), 83.7% (95% CI, 83.6%-83.9%) died in the pre-COVID-19 period and 16.3% (95% CI, 16.1%-16.4%) died in the COVID-19 period, 54.5% (95% CI, 54.2%-54.7%) died at home during the entire study period, and 57.8% (95% CI, 57.5%-58.0%) received SPC at the end of life. In March 2020, home deaths increased by 8.3% (95% CI, 7.4%-9.1%); however, this increase was less marked in Q5 (6.1%; 95% CI, 4.4%-7.8%) than in Q1 (11.4%; 95% CI, 9.6%-13.2%) and Q3 (10.0%; 95% CI, 9.0%-11.1%). There was a simultaneous decrease of 5.3% (95% CI, -6.3% to -4.4%) in the rate of SPC at the end of life, with no significant difference among quintiles. Patients who received SPC at the end of life (vs no SPC) were more likely to die at home before and during the pandemic. However, there was a larger immediate increase in home deaths among those who received no SPC at the end of life vs those who received SPC (Q1, 17.5% [95% CI, 15.2%-19.8%] vs 7.6% [95% CI, 5.4%-9.7%]; Q3, 12.7% [95% CI, 10.8%-14.5%] vs 9.0% [95% CI, 7.2%-10.7%]). For Q5, the increase in home deaths was significant only for patients who did not receive SPC (13.9% [95% CI, 11.9%-15.8%] vs 1.2% [95% CI, -1.0% to 3.5%]). Conclusions and Relevance: These findings suggest that the COVID-19 pandemic was associated with amplified socioeconomic disparities in death at home and SPC delivery at the end of life. Future research should focus on the mechanisms of these disparities and on developing interventions to ensure equitable and consistent SPC access.

Healthcare providers' perspectives on implementing a brief physical activity and diet intervention within a primary care smoking cessation program: a qualitative study.

BACKGROUND: Post-smoking-cessation weight gain can be a major barrier to quitting smoking; however, adding behavior change interventions for physical activity (PA) and diet may adversely affect smoking cessation outcomes. The "Picking up the PACE (Promoting and Accelerating Change through Empowerment)" study assessed change in PA, fruit/vegetable consumption, and smoking cessation by providing a clinical decision support system for healthcare providers to utilize at the intake appointment, and found no significant change in PA, fruits/vegetable consumption, or smoking cessation. The objective of this qualitative study was to explore the factors affecting the implementation of the intervention and contextualize the quantitative results. METHODS: Twenty-five semi-structured interviews were conducted with healthcare providers, using questions based on the National Implementation Research Network's Hexagon Tool. The data were analyzed using the framework's standard analysis approach. RESULTS: Most healthcare providers reported a need to address PA and fruit/vegetable consumption in patients trying to quit smoking, and several acknowledged that the intervention was a good fit since exercise and diet could improve smoking cessation outcomes. However, many healthcare providers mentioned the need to explain the fit to the patients. Social determinants of health (e.g., low income, food insecurity) were brought up as barriers to the implementation of the intervention by a majority of healthcare providers. Most healthcare providers recognized training as a facilitator to the implementation, but time was mentioned as a barrier by many of healthcare providers. Majority of healthcare providers mentioned allied health professionals (e.g., dieticians, physiotherapists) supported the implementation of the PACE intervention. However, most healthcare providers reported a need for individualized approach and adaptation of the intervention based on the patients' needs when implementing the intervention. The COVID-19 pandemic was found to impact the implementation of the PACE intervention based on the Hexagon Tool indicators. CONCLUSION: There appears to be a need to utilize a flexible approach when addressing PA and fruit/vegetable consumption within a smoking cessation program, based on the context of clinic, the patients' it is serving, and their life circumstances. Healthcare providers need support and external resources to implement this particular intervention. NAME OF THE REGISTRY: Clinicaltrials.gov. TRIAL REGISTRATION NUMBER: NCT04223336. DATE OF REGISTRATION: 7 January 2020 Retrospectively registered. URL OF TRIAL REGISTRY RECORD: https://classic. CLINICALTRIALS: gov/ct2/show/NCT04223336 .

MR Imaging of Pediatric Neuroblastoma: Is Gadolinium Enhancement Necessary for Evaluation of Image-Defined-Risk Factors?

Background: Pre-treatment stratification and outcomes of neuroblastoma patients often depend on the assessment of image-defined risk factors (IDRFs) on MR Imaging, usually using Gadolinium-contrast materials which are cautioned in pediatrics. We aimed to address whether gadolinium contrast-enhanced sequences are necessary to identify the presence/absence of IDRFs. Methods: Patients with neuroblastoma with MR imaging were retrospectively identified from 2005 to 2021. Ninety confirmed IDRFs were evaluated in 23 patients. Corresponding MR studies were anonymized, randomized, and independently evaluated by 3 fellowship-trained pediatric radiologists. Each radiologist assessed the studies twice. At the first reading, all enhanced sequences were omitted, while in the second reading, the full study with enhanced sequences were included. Consensus reading was obtained among readers. Inter- and intra-rater agreements using Kappa statistics (κ) as well as the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of non-enhanced MR in assessing IDRFs with respect to enhanced MR were calculated. Results: There were substantial (ĸ: 0.64-0.73) intra-reader agreements, and moderate to substantial (ĸ: 0.57-0.62) inter-reader agreements among radiologists in identifying IDRFs using non-enhanced MR. Non-enhanced MR had a sensitivity of 87.8% (95% CI [79-94]), specificity of 93% (89-96), PPV of 82.3 (73-89), NPV of 95.4 (92-98), and accuracy of 91.6 (88-94) in identifying IDRFs. However, 5/23 patients (21.7%) had a change in staging with the inclusion of contrast sequences. Conclusion: Although contrast sequences have a role in IDRF assessment, the majority can be adequately assessed on MR without gadolinium-contrast enhancement. Validation in a larger cohort is an important next step.

Trends in infection-related and infection-unrelated cancer incidence among people with and without HIV infection in Ontario, Canada, 1996-2020: a population-based matched cohort study using health administrative data.

BACKGROUND: People with HIV infection are at higher risk for certain cancers than the general population. We compared trends in infection-related and infection-unrelated cancers among people with and without HIV infection. METHODS: We conducted a retrospective population-based matched cohort study of adults with and without HIV infection using linked health administrative databases in Ontario, Canada. Participants were matched on birth year, sex, census division (rurality), neighbourhood income quintile and region of birth. We followed participants from cohort entry until the earliest of date of cancer diagnosis, date of death, Nov. 1, 2020, or date of loss to follow-up. Incident cancers identified from Jan. 1, 1996, to Nov. 1, 2020, were categorized as infection-related or-unrelated. We examined calendar periods 1996-2003, 2004-2011 and 2012-2020, corresponding to the early combination antiretroviral therapy (cART), established cART and contemporary cART eras, respectively. We used competing risk analyses to examine trends in cumulative incidence by calendar period, age and sex, and cause-specific hazard ratios (HRs). RESULTS: We matched 20 304 people with HIV infection to 20 304 people without HIV infection. A total of 2437 cancers were diagnosed, 1534 (62.9%) among infected people and 903 (37.0%) among uninfected people. The risk of infection-related cancer by age 65 years for people with HIV infection decreased from 19.0% (95% confidence interval [CI] 15.6%-22.3%) in 1996-2011 to 10.0% (95% CI 7.9%-12.1%) in 2012-2020. Compared to uninfected people, those with HIV infection had similar HRs of infection-unrelated cancer but increased rates of infection-related cancer, particularly among younger age groups (25.1 [95% CI 13.2-47.4] v. 1.9 [95% CI 1.0-3.7] for age 18-39 yr v. ≥ 70 yr); these trends were consistent when examined by sex.Interpretation: We observed significantly higher rates of infection-related, but not infection-unrelated, cancer among people with HIV infection than among uninfected people. The elevated rate of infection-related cancer in 2012-2020 highlights the importance of early and sustained antiretroviral therapy along with cancer screening and prevention measures.

Results from the BETTER WISE trial: a pragmatic cluster two arm parallel randomized controlled trial for primary prevention and screening in primary care during the COVID-19 pandemic.

BACKGROUND: Cancer and chronic diseases are a major cost to the healthcare system and multidisciplinary models with access to prevention and screening resources have demonstrated improvements in chronic disease management and prevention. Research demonstrated that a trained Prevention Practitioner (PP) in multidisciplinary team settings can improve achievement of patient level prevention and screening actions seven months after the intervention. METHODS: We tested the effectiveness of the PP intervention in a pragmatic two-arm cluster randomized controlled trial. Patients aged 40-65 were randomized at the physician level to an intervention group or to a wait-list control group. The intervention consisted of a patient visit with a PP. The PP received training in prevention and screening and use of the BETTER WISE tool kit. The effectiveness of the intervention was assessed using a composite outcome of the proportion of the eligible prevention and screening actions achieved between intervention and control groups at 12-months. RESULTS: Fifty-nine physicians were recruited in Alberta, Ontario, and Newfoundland and Labrador. Of the 1,005 patients enrolled, 733 (72.9%) completed the 12-month analysis. The COVID-19 pandemic occurred during the study time frame at which time nonessential prevention and screening services were not available and in-person visits with the PP were not allowed. Many patients and sites did not receive the intervention as planned. The mean composite score was not significantly higher in patients receiving the PP intervention as compared to the control group. To understand the impact of COVID on the project, we also considered a subset of patients who had received the intervention and who attended the 12-month follow-up visit before COVID-19. This assessment demonstrated the effectiveness of the BETTER visits, similar to the findings in previous BETTER studies. CONCLUSIONS: We did not observe an improvement in cancer and chronic disease prevention and screening (CCDPS) outcomes at 12 months after a BETTER WISE prevention visit: due to the COVID-19 pandemic, the study was not implemented as planned. Though benefits were described in those who received the intervention before COVID-19, the sample size was too small to make conclusions. This study may be a harbinger of a substantial decrease and delay in CCDPS activities under COVID restrictions. TRIAL REGISTRATION: ISRCTN21333761. Registered on 19/12/2016. http://www.isrctn.com/ISRCTN21333761 .

Chronic pain trials often exclude people with comorbid depressive symptoms: A secondary analysis of 346 randomized controlled trials.

BACKGROUND: Chronic pain and depression are common comorbid conditions, but there is limited evidence-based guidance for management of the two conditions together. In recent years, there has been an increase in the number of chronic pain randomized controlled trials that collect depression outcomes, but it is unknown how often these trials include people with depression or significant depressive symptoms. If trials do not include participants representative of real-world populations, evidence and guidance generated from these trials risk being inapplicable for large proportions of the target population, or worse, risk harm. Thus, in order to identify pathways to improve the conduct of clinical trials, the aims of this study were to (1) estimate the proportion of randomized controlled trials evaluating chronic pain interventions and reporting depression outcomes that include participants with significant depressive symptoms; and (2) assess the variability of inclusion proportions by pain type, intervention type, gender, country of origin, and publication year. METHODS: Studies were extracted from an umbrella review of interventions for chronic pain that reported depression outcomes. Screening and data extraction were completed in duplicate and conflicts were resolved by a third author. Randomized controlled trials with at least 50% adult participants and validated depression scales were included, and randomized controlled trials with populations whose mean scores were at or above depression thresholds at baseline were considered to have included participants with depression. RESULTS: Of the 346 randomized controlled trials analyzed, 142 (41%) included participants with depression. Eight pain-type groups and nine intervention types were identified. Randomized controlled trials investigating fibromyalgia and mixed chronic pain had the highest proportion of participants with depression, whereas studies of arthritis and axial pain had among the lowest. Randomized controlled trials from the United States had a significantly lower inclusion proportion compared with non-US studies, especially for studies on arthritis. The increase in inclusion proportion by publication year was driven by the increase in fibromyalgia studies. DISCUSSION AND CONCLUSION: This study highlights opportunities to improve the conduct of chronic pain clinical trials. The majority of randomized controlled trials s analyzed evaluated participants without significant depressive symptoms at baseline, thus the findings synthesized in systematic reviews and subsequent guidelines are most applicable to the subset of real-world populations that do not have significant depressive symptoms. As well, systemic biases around psychological conditions and gender may be important contributors to differences in the study of depression in fibromyalgia compared with common conditions such as arthritis and axial pain. In order to better inform clinical practice, future research must intentionally include individuals with comorbid depression in trials of common chronic pain conditions, and consider methods to mitigate biases that may distort study design.

Opportunities to improve quality of care for cancer survivors in primary care: findings from the BETTER WISE study.

PURPOSE: The BETTER WISE (Building on Existing Tools to Improve Chronic Disease Prevention and Screening in Primary Care for Wellness of Cancer Survivors and Patients) intervention is an evidence-based approach to prevention and screening for cancers and chronic diseases in primary care that also includes comprehensive follow-up for breast, prostate and colorectal cancer survivors. We describe the process of harmonizing cancer survivorship guidelines to create a BETTER WISE cancer surveillance algorithm and describe both the quantitative and qualitative findings for BETTER WISE participants who were breast, prostate or colorectal cancer survivors. We describe the results in the context of the COVID-19 pandemic. METHODS: We reviewed high-quality survivorship guidelines to create a cancer surveillance algorithm. We conducted a cluster randomized trial in three Canadian provinces with two composite index outcome measured 12 months after baseline, and also collected qualitative feedback on the intervention. RESULTS: There were 80 cancer survivors for whom we had baseline and follow-up data. Differences between the composite indices in the two study arms were not statistically significant, although a post hoc analysis suggested the COVID-19 pandemic was a key factor in these results. Qualitative finding suggested that participants and stakeholders generally viewed BETTER WISE positively and emphasized the effects of the pandemic. CONCLUSIONS AND IMPLICATIONS FOR CANCER SURVIVORS: BETTER WISE shows promise for providing an evidence-based, patient-centred, comprehensive approach to prevention, screening and cancer surveillance for cancer survivors in the primary care setting. TRIAL REGISTRATION: ISRCTN21333761. Registered on December 19, 2016, http://www.isrctn.com/ISRCTN21333761 .

Determination of Relative Weightings for Sacroiliac Joint Pathologies in the OMERACT Juvenile Arthritis Magnetic Resonance Imaging Sacroiliac Joint Score.

This study aims to determine the relative weights (point value) of items of the juvenile idiopathic arthritis magnetic resonance imaging-sacroiliac joint scoring system (JAMRIS-SIJ). An adaptive multicriteria decision analysis was performed using the 1000Minds web application to determine the relative weights of the items in the JAMRIS-SIJ inflammation and damage domains. Experts in imaging and rheumatology independently completed a conjoint analysis survey (CAS) to determine the point value of the measurement items of the JAMRIS-SIJ. Each CAS survey question asked the expert to compare two hypothetical patient profiles, which were otherwise similar but different at two items at a time, and to select which item showed a more severe stage of inflammation or osteochondral damage. In addition, experts ranked 14 JAMRIS-SIJ grade only or image + grade patient vignettes while blinded to the CAS-derived weights. The validity of the weighted JAMRIS-SIJ was tested by comparing the expert CAS-weighted score and the image + grade ranking method. Seventeen experts completed the CAS (11 radiologists and 6 rheumatologists). Considering the point value for inflammation domain items, osteitis (24.7%) and bone marrow edema (24.3%) had higher group-averaged percentage weights compared to inflammation in erosion cavity (16.9%), joint space enhancement (13.1%), joint space fluid (9.1%), capsulitis (7.3%), and enthesitis (4.6%). Similarly, concerning the damage domain, ankylosis (41.3%) and erosion (25.1%) showed higher group-averaged weights compared to backfill (13.9%), sclerosis (10.7%), and fat metaplasia lesion (9.1%). The Spearman correlation coefficients of the CAS-weighted vignette order and unweighted JAMRIS-SIJ grade only order vignettes for all experts were 0.79 for inflammation and 0.80 for damage. The correlations of image vignettes among imaging experts to CAS were 0.75 for inflammation and 0.90 for damage. The multicriteria decision analysis identified differences in relative weights among the JAMRIS-SIJ measurement items. The determination of the relative weights provided expert-driven score scaling and face validity for the JAMRIS-SIJ, enabling the future evaluation of its longitudinal construct validity.

Number of epilepsy surgeries has decreased despite an increase in pre-surgical evaluations at a tertiary pediatric epilepsy center in Ontario.

OBJECTIVE: A recent U.S. study reported that the number of epilepsy surgeries has remained stable or declined in recent years despite an increase in pre-surgical evaluation. This study aimed to evaluate trends in pre-surgical evaluation and epilepsy surgery from 2001 to 2019 and to determine whether these trends have changed in the later period (2014-2019) compared to earlier period (2001-2013). METHODS: This study evaluated trends in pre-surgical evaluation and epilepsy surgery at a tertiary pediatric epilepsy center. Children with drug resistant epilepsy who were evaluated for surgery were included. Clinical data, reasons for not undergoing surgery, and surgical characteristics of surgery patients were collected. Overall trends and trends in later period compared to earlier period for pre-surgical evaluation and epilepsy surgery were assessed. RESULTS: There were 1151 children who were evaluated for epilepsy surgery and 546 underwent surgery. There was an upward trend in pre-surgical evaluation in the earlier period (rate ratio [RR]=1.04 (95%CI:1.02-1.07), p<0.001) and the trajectory of presurgical evaluation in the later period was not significantly different to the earlier period (RR=1.00 [95%CI:0.95-1.06], p = 0.88). Among the reasons for not undergoing surgery, failure to localize the seizures occurred more frequently in later period than earlier period (22.6% vs. 17.1% respectively, p = 0.024). For number of surgeries, there was an upward trend between 2001 and 2013 (RR=1.08 [95%CI:1.05-1.11], p<0.001), and a decreasing trend in the later period compared to earlier period (RR=0.91 [95%CI:0.84-0.99], p = 0.029). CONCLUSION: Despite an increasing trend in pre-surgical evaluation, there was a decreasing trend in the number of epilepsy surgery in the later period as there was a larger proportion of patients in whom the seizures could not be localized. Trends in presurgical evaluation and epilepsy surgery will continue to evolve with introduction of technologies such as stereo-EEG and minimally invasive laser therapy.

Factors Associated With Initiation of Antidepressant Medication in Adults With Type 1 and Type 2 Diabetes: A Primary Care Retrospective Cohort Study in Ontario, Canada.

OBJECTIVES: Depression in patients with diabetes mellitus is common and associated with poorer outcomes. This study aims to identify demographic, socioeconomic and medical factors associated with the initiation of antidepressant medication after a diagnosis of diabetes in adult patients without a previous prescription for antidepressants. We also examined frequency of primary care visits in the year after antidepressant initiation compared with the year before treatment began. METHODS: This was a retrospective cohort study using routinely collected electronic medical record data spanning January 2011 to December 2019 from the University of Toronto Practice-based Research Network (UTOPIAN) Data Safe Haven. Our primary outcome was a first prescription for an antidepressant in patients with diabetes. We used a mixed-effects logistic regression model to identify sociodemographic and medical factors associated with this event. RESULTS: Among 22,750 patients with diabetes mellitus, 3,055 patients (13.4%) began taking an antidepressant medication. Increased odds of antidepressant initiation were observed in younger patients (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.39 to 2.26), females (OR, 1.60; 95% CI, 1.46 to 1.7), those receiving insulin treatment (OR, 1.59; 95% CI, 1.43 to 1.78) and cases of polypharmacy (OR, 3.67; 95% CI, 3.29 to 4.11). There was an increase in the mean number of primary care visits from 4.6 to 5.9 per year after antidepressant initiation. CONCLUSIONS: In patients with diabetes, age, sex and medical characteristics were associated with the initiation of antidepressants. These patients accessed primary care more frequently. Screening and prevention of depression, particularly in these subgroups, could reduce its personal and systemic burdens.

Seizure outcome of pediatric magnetic resonance-guided laser interstitial thermal therapy versus open surgery: A matched noninferiority cohort study.

OBJECTIVE: Minimally invasive magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has been proposed as an alternative to open epilepsy surgery, to address concerns regarding the risk of open surgery. Our primary hypothesis was that seizure freedom at 1 year after MRgLITT is noninferior to open surgery in children with drug-resistant epilepsy (DRE). The secondary hypothesis was that MRgLITT has fewer complications and shorter hospitalization than surgery. The primary objective was to compare seizure outcome of MRgLITT to open surgery in children with DRE. The secondary objective was to compare complications and length of hospitalization of the two treatments. METHODS: This retrospective multicenter cohort study included children with DRE treated with MRgLITT or open surgery with 1-year follow-up. Exclusion criteria were corpus callosotomy, neurostimulation, multilobar or hemispheric surgery, and lesion with maximal dimension > 60 mm. MRgLITT patients were propensity matched to open surgery patients. The primary outcome was seizure freedom at 1 year posttreatment. The difference in seizure freedom was compared using noninferiority test, with noninferiority margin of -10%. The secondary outcomes were complications and length of hospitalization. RESULTS: One hundred eighty-five MRgLITT patients were matched to 185 open surgery patients. Seizure freedom at 1 year follow-up was observed in 89 of 185 (48.1%) MRgLITT and 114 of 185 (61.6%) open surgery patients (difference = -13.5%, one-sided 97.5% confidence interval = -23.8% to ∞, pNoninferiority  = .79). The lower confidence interval boundary of -23.8% was below the prespecified noninferiority margin of -10%. Overall complications were lower in MRgLITT compared to open surgery (10.8% vs. 29.2%, respectively, p < .001). Hospitalization was shorter for MRgLITT than open surgery (3.1 ± 2.9 vs. 7.2 ± 6.1 days, p < .001). SIGNIFICANCE: Seizure outcome of MRgLITT at 1 year posttreatment was inferior to open surgery. However, MRgLITT has the advantage of better safety profile and shorter hospitalization. The findings will help counsel children and parents on the benefits and risks of MRgLITT and contribute to informed decision-making on treatment options.

The Impact of a Clinical Decision Support System for Addressing Physical Activity and Healthy Eating During Smoking Cessation Treatment: Hybrid Type I Randomized Controlled Trial.

BACKGROUND: People who smoke have other risk factors for chronic diseases, such as low levels of physical activity and poor diet. Clinical decision support systems (CDSSs) might help health care practitioners integrate interventions for diet and physical activity into their smoking cessation programming but could worsen quit rates. OBJECTIVE: The aims of this study are to assess the effects of the addition of a CDSS for physical activity and diet on smoking cessation outcomes and to assess the implementation of the study. METHODS: We conducted a pragmatic hybrid type I effectiveness-implementation trial with 232 team-based primary care practices in Ontario, Canada, from November 2019 to May 2021. We used a 2-arm randomized controlled trial comparing a CDSS addressing physical activity and diet to treatment as usual and used the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework to measure implementation outcomes. The primary outcome was self-reported 7-day tobacco abstinence at 6 months. RESULTS: We enrolled 5331 participants in the study. Of these, 2732 (51.2%) were randomized to the intervention group and 2599 (48.8%) to the control group. At the 6-month follow-up, 29.7% (634/2137) of respondents in the intervention arm and 27.3% (552/2020) in the control arm reported abstinence from tobacco. After multiple imputation, the absolute group difference was 2.1% (95% CI -0.5 to 4.6; F1,1000.42=2.43; P=.12). Mean exercise minutes changed from 32 (SD 44.7) to 110 (SD 196.1) in the intervention arm and from 32 (SD 45.1) to 113 (SD 195.1) in the control arm (group effect: B=-3.7 minutes; 95% CI -17.8 to 10.4; P=.61). Servings of fruit and vegetables changed from 2.64 servings to 2.42 servings in the intervention group and from 2.52 servings to 2.45 servings in the control group (incidence rate ratio for intervention group=0.98; 95% CI 0.93-1.02; P=.35). CONCLUSIONS: A CDSS for physical activity and diet may be added to a smoking cessation program without affecting the outcomes. Further research is needed to improve the impact of integrated health promotion interventions in primary care smoking cessation programs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04223336 https://www.clinicaltrials.gov/ct2/show/NCT04223336. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/19157.

CT patterns and serial CT Changes in lung Cancer patients post stereotactic body radiotherapy (SBRT).

BACKGROUND: To evaluate computed tomography (CT) patterns of post-SBRT lung injury in lung cancer and identify time points of serial CT changes. MATERIALS AND METHODS: One hundred eighty-three tumors in 170 patients were evaluated on sequential CTs within 29 months (median). Frequencies of post-SBRT CT patterns and time points of initiation and duration were assessed. Duration of increase of primary lesion or surrounding injury without evidence of local recurrence and time to stabilization or local recurrence were evaluated. RESULTS: Post-SBRT CT patterns could overlap in the same patient and were nodule-like pattern (69%), consolidation with ground glass opacity (GGO) (41%), modified conventional pattern (39%), peribronchial/patchy consolidation (42%), patchy GGO (24%), diffuse consolidation (16%), "orbit sign" (21%), mass-like pattern (19%), scar-like pattern (15%) and diffuse GGO (3%). Patchy GGO started at 4 months post-SBRT. Peribronchial/patchy consolidation and consolidation with GGO started at 4 and 5 months respectively. Diffuse consolidation, diffuse GGO and orbit sign started at 5, 6 and 8 months respectively. Mass-like, modified conventional and scar-like pattern started at 8, 12 and 12 months respectively. Primary lesion (n = 11) or surrounding injury (n = 85) increased up to 13 months. Primary lesion (n = 119) or surrounding injury (n = 115) started to decrease at 4 and 9 months respectively. Time to stabilization was 20 months. The most common CT pattern at stabilization was modified conventional pattern (49%), scar-like pattern (23%) and mass-like pattern (12%). Local recurrence (n = 15) occurred at a median time of 18 months. CONCLUSION: Different CT patterns of lung injury post-SBRT appear in predictable time points and have variable but predictable duration. Familiarity with these patterns and timeframes of appearance helps differentiate them from local recurrence.

The burden of cancer among people living with HIV in Ontario, Canada, 1997-2020: a retrospective population-based cohort study using administrative health data.

BACKGROUND: With combination antiretroviral therapy (ART) and increased longevity, cancer is a leading cause of morbidity among people with HIV. We characterized trends in cancer burden among people with HIV in Ontario, Canada, between 1997 and 2020. METHODS: We conducted a population-based, retrospective cohort study of adults with HIV using linked administrative health databases from Jan. 1, 1997, to Nov. 1, 2020. We grouped cancers as infection-related AIDS-defining cancers (ADCs), infection-related non-ADCs (NADCs) and infection-unrelated cancers. We calculated age-standardized incidence rates per 100 000 person-years with 95% confidence intervals (CIs) using direct standardization, stratified by calendar period and sex. We also calculated limited-duration prevalence. RESULTS: Among 19 403 adults living with HIV (79% males), 1275 incident cancers were diagnosed. From 1997-2000 to 2016- 2020, we saw a decrease in the incidence of all cancers (1113.9 [95% CI 657.7-1765.6] to 683.5 [95% CI 613.4-759.4] per 100 000 person-years), ADCs (403.1 [95% CI 194.2-739.0] to 103.8 [95% CI 79.2-133.6] per 100 000 person-years) and infection-related NADCs (196.6 [95% CI 37.9-591.9] to 121.9 [95% CI 94.3-154.9] per 100 000 person-years). The incidence of infection-unrelated cancers was stable at 451.0 per 100 000 person-years (95% CI 410.3-494.7). The incidence of cancer among females increased over time but was similar to that of males in 2016-2020. INTERPRETATION: Over a 24-year period, the incidence of cancer decreased overall, largely driven by a considerable decrease in the incidence of ADC, whereas the incidence of infection-unrelated cancer remained unchanged and contributed to the greatest burden of cancer. These findings could reflect combination ART-mediated changes in infectious comorbidity and increased life expectancy; targeted cancer screening and prevention strategies are needed.

Urinary interleukin-9 in youth with type 1 diabetes mellitus.

AIMS: Interleukin-9 (IL-9) attenuates podocyte injury in experimental kidney disease, but its role in diabetic nephropathy is unknown. We sought to relate urinary IL-9 levels to the release of podocyte-derived extracellular vesicles (EVs) in youth with type 1 diabetes. We related urinary IL-9 levels to clinical variables and studied interactions between urinary IL-9, vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) on urinary albumin/creatinine ratio (ACR) a functional measure of podocyte injury. METHODS: We performed an analysis of urine samples and clinical data from a cohort of youth with type 1 diabetes (n = 53). Cytokines were measured using a Luminex platform (Eve Technologies), and nanoscale flow cytometry was employed to quantify urinary podocyte-derived EVs. All urinary measures were normalized to urinary creatinine. RESULTS: Mean age was 14.7 ± 1.6 years, and the mean time from diagnosis was 6.7 ± 2.9 years. Mean HbA1c was 70.3 ± 13.9 mmol/mol, mean ACR was 1.3 ± 1.9 mg/mmol, and mean eGFR was 140.3 ± 32.6 ml/min/1.73 m2. IL-9 was inversely related to podocyte EVs (r = - 0.56, p = 0.003). IL-9 was also inversely related to blood glucose, HbA1C and eGFR (r = - 0.44, p = 0.002; r = - 0.41, p = 0.003; r = - 0.49, p < 0.001, respectively) and positively correlated with systolic BP (r = 0.30, p = 0.04). There was a significant interaction between IL-9, EVs and ACR (p = 0.0143), and the relationship between IL-9 and ACR depended on VEGF (p = 0.0083), TNFα (p = 0.0231) and IL-6 levels (p = 0.0178). CONCLUSIONS: IL-9 is associated with podocyte injury in early type 1 diabetes, and there are complex interactions between urinary IL-9, inflammatory cytokines and ACR.

Ovarian cancer incidence and death in average-risk women undergoing bilateral salpingo-oophorectomy at benign hysterectomy.

BACKGROUND: Opportunistic bilateral salpingo-oophorectomy is often offered to patients undergoing benign hysterectomy to prevent ovarian cancer, but the magnitude of risk reduction obtained with bilateral salpingo-oophorectomy in this population remains unclear and must be weighed against potential risks of ovarian hormone deficiency. OBJECTIVE: This study aimed to quantify the relative and absolute risk reduction in ovarian cancer incidence and death associated with bilateral salpingo-oophorectomy at the time of benign hysterectomy. STUDY DESIGN: We performed a population-based cohort study of all adult women (≥20 years) undergoing benign hysterectomy from 1996 to 2010 in Ontario, Canada. Patients with ovarian pathology, previous breast or gynecologic cancer, or evidence of genetic susceptibility to malignancy were excluded. Inverse probability of treatment-weighted Fine-Gray subdistribution hazard models were used to quantify the effect of bilateral salpingo-oophorectomy on ovarian cancer incidence and death while accounting for competing risks and adjusting for demographic characteristics, gynecologic conditions, and comorbidities. Analyses were performed in all women and specifically in women of postmenopausal age (≥50 years) at the time of hysterectomy. RESULTS: We identified 195,282 patients (bilateral salpingo-oophorectomy, 24%; ovarian conservation, 76%) with a median age of 45 years (interquartile range, 40-51 years). Over a median follow-up of 16 years (interquartile range, 12-20 years), 548 patients developed ovarian cancer (0.3%), and 16,170 patients (8.3%) died from any cause. Bilateral salpingo-oophorectomy was associated with decreased ovarian cancer incidence (hazard ratio, 0.23; 95% confidence interval, 0.14-0.38; P<.001) and decreased ovarian cancer death (hazard ratio, 0.30; 95% confidence interval, 0.16-0.57; P<.001). At 20 years follow-up, the weighted cumulative incidences of ovarian cancer were 0.08% and 0.46% with bilateral salpingo-oophorectomy and ovarian conservation, respectively, yielding an absolute risk reduction of 0.38% (95% confidence interval, 0.32-0.45; number needed to treat, 260). After restricting to women aged ≥50 years at hysterectomy, the absolute risk reduction was 0.62% (95% confidence interval, 0.47-0.77; number needed to treat, 161). CONCLUSION: Bilateral salpingo-oophorectomy resulted in a significant absolute reduction in ovarian cancer among women undergoing benign hysterectomy. Population-average risk estimates derived in this study should be balanced against other potential implications of bilateral salpingo-oophorectomy to inform practice guidelines, patient decision-making, and surgical management.

Primary Care Continuity and Wait Times to Receiving Breast Cancer Chemotherapy: A Population-Based Retrospective Cohort Study Using CanIMPACT Data.

(1) Background: Wait times to chemotherapy are associated with morbidity and mortality in breast cancer patients; however, it is unclear how primary care physician (PCP) continuity impacts these wait times, or whether this association is different in immigrants, who experience cancer care inequities. We assessed the association between PCP continuity and the contact-to-chemotherapy interval (wait time from when a patient first presents to healthcare to the first day of receiving breast cancer chemotherapy), with a specific look at the immigrant population. (2) Methods: Population-based, retrospective cohort study of women who were diagnosed with stage I-III breast cancer in Ontario who received surgery and adjuvant chemotherapy. We used quantile regression at the median and 90th percentile to quantify the effect of PCP continuity on the contact-to-chemotherapy interval, performing a separate analysis on the immigrant population. (3) Results: Among 12,781 breast cancer patients, including 1706 immigrants, the median contact-to-chemotherapy interval (126 days) was 3.21 days shorter (95% confidence interval (CI) 0.47-5.96) in symptom-detected patients with low PCP continuity, 10.68 days shorter (95% CI 5.36-16.00) in symptom-detected patients with no baseline PCP visits and 17.43 days longer (95% CI 0.90-34.76) in screen-detected immigrants with low PCP continuity compared to the same groups with high PCP continuity. (4) Conclusions: Higher PCP continuity was not associated with a change in the contact-to-chemotherapy interval for most of our study population, but was associated with a marginally longer interval in our symptom-detected population and a shorter contact-to-chemotherapy interval in screen-detected immigrants. This highlights the importance of PCP continuity among immigrants with positive screening results. Additionally, having no PCP visits at baseline was associated with a shorter contact-to-chemotherapy interval in symptom-detected patients.

Association of bilateral salpingo-oophorectomy with all cause and cause specific mortality: population based cohort study.

OBJECTIVES: To determine if bilateral salpingo-oophorectomy, compared with ovarian conservation, is associated with all cause or cause specific death in women undergoing hysterectomy for non-malignant disease, and to determine how this association varies with age at surgery. DESIGN: Population based cohort study. SETTING: Ontario, Canada from 1 January 1996 to 31 December 2015, and follow-up to 31 December 2017. PARTICIPANTS: 200 549 women (aged 30-70 years) undergoing non-malignant hysterectomy, stratified into premenopausal (<45 years), menopausal transition (45-49 years), early menopausal (50-54 years), and late menopausal (≥55 years) groups according to age at surgery; median follow-up was 12 years (interquartile range 7-17). EXPOSURES: Bilateral salpingo-oophorectomy versus ovarian conservation. MAIN OUTCOMES MEASURES: The primary outcome was all cause death. Secondary outcomes were non-cancer and cancer death. Within each age group, overlap propensity score weighted survival models were used to examine the association between bilateral salpingo-oophorectomy and mortality outcomes, while adjusting for demographic characteristics, gynaecological conditions, and comorbidities. To account for comparisons in four age groups, P<0.0125 was considered statistically significant. RESULTS: Bilateral salpingo-oophorectomy was performed in 19%, 41%, 69%, and 81% of women aged <45, 45-49, 50-54, and ≥55 years, respectively. The procedure was associated with increased rates of all cause death in women aged <45 years (hazard ratio 1.31, 95% confidence interval 1.18 to 1.45, P<0.001; number needed to harm 71 at 20 years) and 45-49 years (1.16, 1.04 to 1.30, P=0.007; 152 at 20 years), but not in women aged 50-54 years (0.83, 0.72 to 0.97, P=0.018) or ≥55 years (0.92, 0.82 to 1.03, P=0.16). Findings in women aged <50 years were driven largely by increased non-cancer death. In secondary analyses identifying a possible change in the association between bilateral salpingo-oophorectomy and all cause death with advancing age at surgery, the hazard ratio gradually decreased during the menopausal transition and remained around 1 at all ages thereafter. CONCLUSION: In this observational study, bilateral salpingo-oophorectomy at non-malignant hysterectomy appeared to be associated with increased all cause mortality in women aged <50 years, but not in those aged ≥50 years. While caution is warranted when considering bilateral salpingo-oophorectomy in premenopausal women without indication, this strategy for ovarian cancer risk reduction does not appear to be detrimental to survival in postmenopausal women.

A Population-Based Study of COVID-19 Infection Among Childhood Cancer Survivors.

Childhood cancer survivors are known to be at risk of chronic co-morbidities, although their risk of COVID-19 infection remains uncertain. Understanding the risk of COVID-19 in this population is necessary to counsel survivors and inform potential mitigation strategies. The objective of this study was to determine whether the rates of COVID-19 infection differed between childhood cancer survivors and the general population. Administrative health care data from a population-based registry of children and adolescents diagnosed with cancer in Ontario, Canada, were linked with a universal health insurance registry and a repository of laboratory data. Rates of COVID-19 testing, test positivity and infection between March 1, 2020 and March 31, 2021 among childhood cancer survivors (n = 10 242) were compared to matched controls from the general population (n = 49 068). Compared to the general population, childhood cancer survivors were more likely to have COVID-19 testing (35.9% [95% CI, 34.5-37.4%] vs. 32.0% [95% CI, 31.4-32.6%]), but had a lower likelihood of positive COVID-19 result among those tested (4.3% [95% CI, 3.6-4.9%] vs. 5.5% [95% CI, 5.1-5.8%]) and a similar rate of infection among all subjects at risk (1.5% [95% CI, 1.3-1.8%] vs. 1.7% [95% CI, 1.6-1.9%]). These findings can inform counseling of survivors and clinician recommendations for this population.