Age-related trends in the incidence of metastatic colorectal cancer from 2010 to 2019 in the USA.

Aim: To evaluate temporal changes in metastatic colorectal cancer (mCRC), incidence, and use of chemotherapy treatment by age group using real-world data (RWD) from the USA. Methods: A retrospective, observational study describing temporal trends in mCRC incidence and FOLFOXIRI treatment by age group using a nationwide database of commercially and Medicare Advantage-insured patients from 2010 to 2019. Results: Incidence of mCRC increased by 22.1 and 14.9% in the 18-49 and 50-64 years cohorts, respectively, and decreased by 21.6% in the ≥65 years cohort. Overall, younger patients were more likely to receive FOLFOXIRI treatment versus older patients. Conclusion: The shifting age distribution of mCRC should be considered when recommending screening and treatment. Further research is needed to inform age-specific treatment guidelines.

What is this article about? This article reports the results of a study that used a US database of commercially and Medicare Advantage-insured adults to evaluate how the number of adults with metastatic colorectal cancer (mCRC) in three age groups (18­49 years, 50­64 years and 65 years and over) changed from 2010 to 2019. The study also looked at the use of an aggressive chemotherapy treatment, known as 5-fluorouracil, oxaliplatin, leucovorin calcium and irinotecan (FOLFOXIRI), by age group. What were the results? Overall, 23,970 adults with mCRC were included in the study. From 2010 to 2019, the number of adults with mCRC increased by 22.1% among those aged 18­49 years, increased by 14.9% among those aged 50­64 years, and decreased by 21.6% among those aged 65 years and over. There were some differences between age groups; a higher percentage of younger patients (18­49 years) were Hispanic or Asian, and from the South compared with the older age groups. In comparison, those aged 65 years and over were more likely to be from the West and Northeast of the USA. The study also found that a higher proportion of those aged 18­49 years received FOLFOXIRI (8.4%) compared with adults aged 50­64 years (4.4%) and 65 years and over (1.9%). What do the results of the study mean? Healthcare providers should be aware that early-onset mCRC is becoming more common and consider this when recommending screening and treatment.

A systematic evidence map of chronic inflammation and immunosuppression related to per- and polyfluoroalkyl substance (PFAS) exposure.

BACKGROUND: The ability to induce chronic inflammation and immunosuppression are two key characteristics of carcinogens and important forms of immunotoxicity. The National Toxicology Program (NTP) evaluated the immunotoxicity of two per- and polyfluoroalkyl substances (PFASs), PFOA (perfluorooctanoic acid) and PFOS (perfluorooctane sulfonate), in 2016. However, the potential pro-inflammatory and immunosuppressive effects of other PFASs remain largely uncharacterized. METHODS: We developed an expanded set of search terms pertaining to the chronic inflammatory and immunosuppressive effects of PFASs based on those of the International Agency for Research on Cancer (IARC) and NTP. To confirm searching effectiveness and scope, we compared our search term results with those of IARC and NTP for both PFASs and two other known carcinogens, chromium (VI) and benzene. Systematic evidence maps (SEMs) were also produced using Tableau to visualize the distribution of study numbers and types reporting immunotoxic effects and specific biomarkers elicited by PFAS exposures. RESULTS: In total, 1155 PFAS studies were retrieved, of which 321 qualified for inclusion in our dataset. Using our search terms, we identified a greater number of relevant studies than those obtained using IARC and NTP's search terms. From the SEM findings, increased cytokine production strengthened an association between PFAS exposure and chronic inflammation, and decreased B-cell activation and altered levels of T-cell subtypes and immunoglobulins confirmed PFAS-induced immunosuppression. CONCLUSION: Our SEM findings confirm that several PFASs commonly found in both in the environment, including those that are lesser-known, may induce immunosuppression and chronic inflammation, two key characteristics of carcinogens. This approach, including development of search terms, study screening process, data coding, and evidence mapping visualizations, can be applied to other key characteristics of chemical carcinogens.

Real-world outcomes of second novel hormonal therapy or radium-223 following first novel hormonal therapy for mCRPC.

Aim: To evaluate real-world clinical outcomes of radium-223 or alternative novel hormonal therapy (NHT) following first-line NHT for metastatic castration-resistant prostate cancer (mCRPC). Patients & methods: Retrospective analysis of the US Flatiron database (ClinicalTrials.gov identifier: NCT03896984). Results: In the radium-223 cohort (n = 120) versus the alternative NHT cohort (n = 226), proportionally more patients had prior symptomatic skeletal events and bone-only metastases, and first-line NHT duration was shorter. Following second-line therapy, 49 versus 39% of patients received subsequent life-prolonging therapy; of these, 47 versus 76% received taxane. Median overall survival was 10.8 versus 11.2 months. Conclusion: Real-world patients with mCRPC had similar median overall survival following second-line radium-223 or alternative NHT after first-line NHT. Many patients received subsequent therapy, with less taxane use after radium-223.

Lay abstract Patients with metastatic castration-resistant prostate cancer are often first treated with novel hormonal therapy (NHT) using abiraterone or enzalutamide. To aid decisions about what treatment to use next, we reviewed information about patients who were treated with an alternative NHT (226 patients) or the nuclear medicine radium-223 (120 patients) after the first NHT. Most patients given radium-223 had cancer that had spread to their bones only, whereas many patients given an alternative NHT had cancer in their bones and other parts of their body. Around one in four patients given radium-223 and one in five given an alternative NHT had symptoms related to their bone metastases after starting treatment. Five in every ten patients given radium-223 received further therapy, including chemotherapy in 50% of these patients, while four in every ten patients given an alternative NHT received further therapy, including chemotherapy in 75%. On average, patients lived for almost a year after starting radium-223 or an alternative NHT.

Assessing the efficacy-effectiveness gap for cancer therapies: A comparison of overall survival and toxicity between clinical trial and population-based, real-world data for contemporary parenteral cancer therapeutics.

BACKGROUND: Although increasing evidence has suggested that an efficacy-effectiveness gap exists between clinical trial (CT) and real-world evidence (RWE), to the authors' knowledge, the magnitude of this difference remains undercharacterized. The objective of the current study was to quantify the magnitude of survival and toxicity differences between CT and RWE for contemporary cancer systemic therapies. METHODS: Patients receiving cancer therapies funded under Cancer Care Ontario's New Drug Funding Program (NDFP) were identified. Landmark CTs with data regarding survival and adverse events (AEs) for each drug indication were identified. RWE for survival and hospitalization rates during treatment were ascertained through Canadian population-based databases. The efficacy-effectiveness gap for each drug indication was calculated as the difference between RWE and CT data for median overall survival (OS), 1-year OS, and generated hazard ratios (HRs) with 95% CIs from Kaplan-Meier OS curves. Toxicity differences were calculated as the difference between RWE of hospitalization rates and CT serious AE rates. RESULTS: Twenty-nine indications from 20 systemic therapies were included. Twenty-eight of 29 indications (97%) demonstrated worse survival in RWE, with a median OS difference of 5.2 months (interquartile range, 3.0-12.1 months). Lower effectiveness in RWE also was demonstrated through a meta-analysis of an OS hazard ratio of 1.58 (95% CI, 1.39-1.80). The median difference between RWE for hospitalization rates and CT serious AEs was 14% (95% CI, 9%-22%). CONCLUSIONS: An efficacy-effectiveness gap exists for contemporary cancer systemic therapies, with a 5.2-month lower median OS observed in RWE compared with CT data. These data supports the use of RWE to better inform real-world decision making regarding the use of cancer systemic therapies.

Benzene-associated immunosuppression and chronic inflammation in humans: a systematic review.

OBJECTIVE: Recent evidence has accumulated that the immune system is intimately intertwined with cancer development. Two key characteristics of carcinogens in which the immune system plays a central role are chronic inflammation and immunosuppression. In this systematic review, we investigated the association of chronic inflammatory and immunosuppressive outcomes with benzene, a widely used industrial chemical. Benzene has been confirmed to cause acute myeloid leukaemia and suspected to cause non-Hodgkin lymphoma, two cancers of the blood-forming system that affect immune cells. METHODS: We systematically searched PubMed and Embase for all relevant studies using a combination of Medical Subject Headings (MeSH) and selected key words. The detailed review protocol, including search strategy, was registered with PROSPERO, the international prospective register of systematic reviews (#CRD42019138611). RESULTS: Based on all human studies selected in the final review, we report new evidence of a benzene-induced immunosuppressive effect on the adaptive immune system and activation of the innate immune system to cause inflammation. In particular, benzene significantly lowers the number of white blood cells, particularly lymphocytes such as CD4+ T-cells, B-cells and natural killer cells, and increases proinflammatory biomarkers at low levels of exposure. CONCLUSION: To the best of our knowledge, this is the first comprehensive review of benzene's immunotoxicity in humans. Based on results obtained from this review, we propose two potential immunotoxic mechanisms of how benzene induces leukaemia/lymphoma: (1) cancer invasion caused by proinflammatory cytokine production, and (2) cancer promotion via impaired immunosurveillance. Further studies will be required to confirm the connection between benzene exposure and its effects on the immune system.

Periodic health visits by primary care practice model, a population-based study using health administrative data.

BACKGROUND: The general health check, which includes the periodic health visit and annual physical exam, is not recommended to maintain the health of asymptomatic adults with no risk factors. Different funding mechanisms for primary care may be associated with the provision of service delivery according to recommended guidelines. We sought to determine how use of the periodic health visit for healthy individuals without comorbidities, despite evidence against its use, differed by primary care model. METHODS: Population-based cross-sectional study using linked health and administrative datasets in Ontario, Canada, where most residents are insured for physician services through Ontario's single payer, provincially funded Ontario Health Insurance Plan. Participants included all living adults (> 19 years) in Ontario on January 1st, 2014, eligible for the Ontario Health Insurance Plan. Primary care enrollment model was the main exposure and included traditional fee-for-service, enhanced fee-for-service, capitation, team-based care, other (including salaried), and unenrolled. The main outcome measure was receipt of a periodic health visit during 2014. Age-sex standardized rates of periodic health visits performed during the one-year study period were analyzed by number of comorbid conditions. RESULTS: Of 10,712,804 adults in Ontario, 2,350,386 (21.9%) had a periodic health visit in 2014. The age-sex standardized rate was 6.1% (95% confidence interval [CI] 6.0, 6.1%) for healthy individuals. In the traditional fee-for-service model, the periodic health visit was performed for 55.3% (95% CI 54.4, 56.3%) of healthy individuals versus 10.2% (95% CI 10.0, 10.3%) in team-based care. Periodic health visit rates varied by primary care provider models. Traditional and enhanced fee-for-service models had higher rates across all comorbidity groups. CONCLUSIONS: Patients whose primary care physicians are funded exclusively through fee-for-service had the highest rates of periodic health visits in healthy individuals. Primary care reform initiatives must consider the influence of remuneration on providing evidence-based primary care.

The Incidence of Major Cardiovascular Events in Immigrants to Ontario, Canada: The CANHEART Immigrant Study.

BACKGROUND: Immigrants from ethnic minority groups represent an increasing proportion of the population in many high-income countries but little is known about the causes and amount of variation between various immigrant groups in the incidence of major cardiovascular events. METHODS AND RESULTS: We conducted the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) Immigrant study, a big data initiative, linking information from Citizenship and Immigration Canada's Permanent Resident database to nine population-based health databases. A cohort of 824 662 first-generation immigrants aged 30 to 74 as of January 2002 from eight major ethnic groups and 201 countries of birth who immigrated to Ontario, Canada between 1985 and 2000 were compared to a reference group of 5.2 million long-term residents. The overall 10-year age-standardized incidence of major cardiovascular events was 30% lower among immigrants compared with long-term residents. East Asian immigrants (predominantly ethnic Chinese) had the lowest incidence overall (2.4 in males, 1.1 in females per 1000 person-years) but this increased with greater duration of stay in Canada. South Asian immigrants, including those born in Guyana had the highest event rates (8.9 in males, 3.6 in females per 1000 person-years), along with immigrants born in Iraq and Afghanistan. Adjustment for traditional risk factors reduced but did not eliminate differences in cardiovascular risk between various ethnic groups and long-term residents. CONCLUSIONS: Striking differences in the incidence of cardiovascular events exist among immigrants to Canada from different ethnic backgrounds. Traditional risk factors explain part but not all of these differences.

Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis.

BACKGROUND: Current observational studies on warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation (AF) undergoing dialysis found conflicting results. METHODS AND RESULTS: We conducted a population-based retrospective cohort study of patients aged ≥65 years admitted to a hospital with a primary or secondary diagnosis of AF, in Quebec and Ontario, Canada from 1998 to 2007. The AF cohort was grouped into dialysis (hemodialysis and peritoneal dialysis) and nondialysis patients and into warfarin and no-warfarin users according to the first prescription filled for warfarin within 30 days after AF hospital discharge. We determined the association between warfarin use and the risk for stroke and bleeding in dialysis and nondialysis patients. The cohort comprised 1626 dialysis patients and 204 210 nondialysis patients. Among dialysis patients, 46% (756/1626) patients were prescribed warfarin. Among dialysis patients, warfarin users had more congestive heart failure and diabetes mellitus, but fewer prior bleeding events in comparison with the no-warfarin users. Among dialysis patients, warfarin use, in comparison with no-warfarin use, was not associated with a lower risk for stroke (adjusted hazard ratio, 1.14; 95% confidence interval, 0.78-1.67) but was associated with a 44% higher risk for bleeding (adjusted hazard ratio, 1.44; 95% confidence interval, 1.13-1.85) after adjusting for potential confounders. Propensity score-adjusted analyses yielded similar results. CONCLUSIONS: Our results suggest that warfarin use is not beneficial in reducing stroke risk, but it is associated with a higher bleeding risk in patients with AF undergoing dialysis.

Serum ferritin is a biomarker for liver mortality in the Hemochromatosis and Iron Overload Screening Study.

BACKGROUND: We identified no reports of long-term follow-up of participants in hemochromatosis screening programs. We evaluated causes of death and survival in non-C282Y homozygous Canadian participants in the primary care-based hemochromatosis and iron overload screening (HEIRS) study. MATERIAL AND METHODS: Initial screening (IS) included transferrin saturation (TS), serum ferritin (SF), HFE genotyping (C282Y, H63D), and health questionnaire responses. By definition, participants without C282Y or H63D had HFE wt/wt. We linked 20,306 Canadian participants to the Ontario Death Registry for dates and causes of death 9 y after IS. We computed Cox proportional hazards to identify factors with increased death risks and Kaplan-Meier curves to estimate survival of non-C282Y homozygous participants with SF ≤ 1,000 µg/L and > 1,000 µg/dL. RESULTS: There were 19,052 evaluable participants (IS mean age 49 y; 60% women; 93 C282Y homozygotes). There were 988 deaths. Significantly increased hazard ratios for all-cause mortality were positively associated with TS, SF, men, and C282Y homozygosity, and liver disease, diabetes, and heart failure reports. Non-C282Y homozygous participants with SF > 1,000 µg/L had lower survival than those with SF ≤ 1,000 µg/L (p < 0.0001). CONCLUSIONS: Nine years after initial screening, non-C282Y homozygous participants and SF > 1,000 µg/L was associated with decreased survival.

Adverse effects associated with transcatheter aortic valve implantation: a meta-analysis of contemporary studies.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has emerged as an important treatment for patients with severe symptomatic aortic stenosis who are at high operative risk, but accurate estimates of serious adverse effects in contemporary practice are not available. PURPOSE: To quantify the adverse effects associated with TAVI, and to evaluate whether the type of transcatheter valve and the route of valve implantation are associated with differences in adverse outcomes. DATA SOURCE: PubMed to 5 May 2012. STUDY SELECTION: All studies that included at least 100 patients who had TAVI and reported at least 1 outcome of interest. DATA EXTRACTION: Two reviewers abstracted the data independently. A random-effects model was used to combine data on adverse outcomes and conduct stratified analyses. DATA SYNTHESIS: A total of 49 studies enrolling 16 063 patients met the inclusion criteria. Overall 30-day and 1-year survival after TAVI were 91.9% (95% CI, 91.1% to 92.8%) and 79.2% (CI, 76.9% to 81.4%), respectively. Heart block requiring permanent pacemaker implantation was the most common adverse outcome (13.1%) and was 5 times more common with the CoreValve (Medtronic, Minneapolis, Minnesota) than the Sapien valve (Edwards Lifesciences, Irving, California) implanted using the transarterial route (25.2% vs. 5.0%, respectively). The overall rate of vascular complications was 10.4% and was highest with transarterial implantation of the Sapien valve (22.3%). Acute renal failure requiring renal replacement therapy was the third most common complication, occurring in 4.9% of patients. LIMITATION: Rates of major vascular complications may be overestimated owing to rapidly evolving TAVI technology. CONCLUSION: The most common adverse effects associated with TAVI are heart block, vascular complications, and renal failure. The type of transcatheter valve and the route of implantation are associated with observed variations in the risks for some adverse effects. PRIMARY FUNDING SOURCE: Heart and Stroke Foundation of Canada.

Predictors of normal coronary arteries at coronary angiography.

BACKGROUND: Coronary angiograms are important in the diagnostic workup of patients with suspected coronary artery disease. However, little is known about the clinical predictors of normal angiograms and whether this rate varies across different cardiac centers in Ontario. METHODS: We conducted a study using the Cardiac Care Network Variations in Revascularization Practice in Ontario database of 2,718 patients undergoing an index cardiac catheterization for an indication of stable angina between April 2006 and March 2007 at one of 17 cardiac hospitals in Ontario. We determined predictors of normal coronary angiograms (0% coronary stenosis) and compared rates of patients with normal catheterizations across centers. RESULTS: Overall, 41.9% of patients with stable angina had a normal catheterization. A multivariate model demonstrated female gender to be the strongest predictor of a normal angiogram (odds ratio 3.55, 95% CI 2.93-4.28). In addition, atypical ischemic symptoms or no symptoms, the absence of diabetes, hyperlipidemia, smoking history, peripheral vascular disease, and angiography performed at a nonteaching site were associated with higher rates of normal catheterization. The rate of normal angiograms studied varied from 18.4% to 76.9% across hospitals and was more common in community compared with academic settings (47.1% vs 35.4%, P < .001). CONCLUSIONS: The absence of traditional cardiac risk factors, female gender, and lack of typical angina symptoms are all associated with a higher frequency of normal cardiac catheterizations. The wide variation in Ontario in the frequency of normal angiograms in patients with stable angina suggests that there are opportunities to improve patient case selection.

Prevalence and extent of obstructive coronary artery disease among patients undergoing elective coronary catheterization in New York State and Ontario.

IMPORTANCE: Prior studies have shown that physicians in New York State (New York) perform twice as many cardiac catheterizations per capita as those in Ontario for stable patients. However, the role of patient selection in these findings and their implications for detection of obstructive coronary artery disease (CAD) are largely unknown. OBJECTIVE: To evaluate the extent of obstructive CAD and to compare the probability of detecting obstructive CAD for patients undergoing cardiac catheterization. DESIGN, SETTING, AND PATIENTS: An observational study was conducted involving patients without a history of cardiac disease who underwent elective cardiac catheterization between October 1, 2008, and September 30, 2011. Obstructive CAD was defined as diameter stenosis of 50% or more in the left main coronary artery or stenosis of 70% or more in a major epicardial vessel. MAIN OUTCOMES AND MEASURES: Observed rates and predicted probabilities of obstructive CAD. Predicted probabilities were estimated using logistic regression models. RESULTS: A total of 18,114 patients from New York and 54,933 from Ontario were included. The observed rate of obstructive CAD was significantly lower in New York at 30.4% (95% CI, 29.7%-31.0%) than in Ontario at 44.8% (95% CI, 44.4%-45.3%; P < .001). The percentage of patients with left main or 3-vessel CAD was also significantly lower in New York than in Ontario (7.0% [95% CI, 6.6%-7.3%] vs 13.0% [95% CI, 12.8%-13.3%]; P < .001). In New York, a substantially higher percentage of patients with low predicted probability of obstructive CAD underwent cardiac catheterization; for example, only 19.3% (95% CI, 18.7%-19.9%) of patients undergoing cardiac catheterization in New York had a greater than 50% predicted probability of having obstructive CAD than those in Ontario at 41% (95% CI, 40.6%-41.4%; P < .001). At 30 days, crude mortality for patients undergoing cardiac catheterization was slightly higher in New York at 0.65% (90 of 13,824; 95% CI, 0.51%-0.78%) than in Ontario at 0.38% (153 of 40,794; 95% CI, 0.32%-0.43%; P < .001). CONCLUSIONS AND RELEVANCE: In Ontario compared with New York State, patients undergoing elective cardiac catheterization were significantly more likely to have obstructive CAD. This appears to be related to a higher percentage of patients in New York with low predicted probability of CAD undergoing cardiac catheterization.

Real-world outcomes associated with vonoprazan-based versus proton pump inhibitor-based therapy for Helicobacter pylori infection in Japan.

Background: Japanese guidelines recommend triple therapy with vonoprazan or a proton pump inhibitor (PPI) in combination with antibiotics to treat Helicobacter pylori (H. pylori) infection. While studies have shown improved eradication rates and reduced costs with vonoprazan versus PPIs, there is little data describing healthcare resource use (HCRU) and treatment patterns. Objectives: To compare patients treated with a vonoprazan-based or PPI-based regimen for H. pylori infection in Japan in terms of their characteristics, HCRU, healthcare costs, clinical outcomes, and treatment patterns. Design: Retrospective matched cohort. Methods: We used data from the Japan Medical Data Center claims database (July 2014-January 2020) to identify adult patients with H. pylori infection and a first observed use of vonoprazan or a PPI in 2015 or later (index date). Patients prescribed a vonoprazan-based or a PPI-based regimen were matched 1:1 using propensity score matching. HCRU, healthcare costs, diagnostic tests, a proxy for H. pylori eradication (i.e. no triple therapy with amoxicillin in combination with metronidazole or clarithromycin >30 days after the index date), and second-line treatment were described during the 12-month follow-up period. Results: Among 25,389 matched pairs, vonoprazan-treated patients had fewer all-cause and H. pylori-related inpatient stays and outpatient visits than PPI-treated patients, resulting in lower all-cause healthcare costs [185,378 Japanese yen (JPY) versus 230,876 JPY, p < 0.001]. Over 80% of patients received a post-treatment test for H. pylori. Fewer vonoprazan-treated than PPI-treated patients subsequently received an additional triple regimen for H. pylori infection (7.1% versus 20.0%, p < 0.001) or a prescription for vonoprazan or a PPI as monotherapy (12.4% versus 26.4%, p < 0.001) between 31 days and 12 months after the index date. Conclusion: Patients with H. pylori infection who were treated with vonoprazan-based therapy had lower rates of subsequent H. pylori treatment, lower overall and H. pylori-related HCRU, and lower healthcare costs than patients treated with PPI-based therapy.

Real-world comparative effectiveness of acalabrutinib and ibrutinib in patients with chronic lymphocytic leukemia.

Novel agents, including Bruton tyrosine kinase inhibitors (BTKis), have become the standard of care for patients with chronic lymphocytic leukemia (CLL). We conducted a real-world retrospective analysis of patients with CLL treated with acalabrutinib vs ibrutinib using the Flatiron Health database. Patients with CLL were included if they initiated acalabrutinib or ibrutinib between 1 January 2018 and 28 February 2021. The primary outcome of interest was time to treatment discontinuation (TTD). Kaplan-Meier analysis was used to estimate unweighted and weighted median TTD. A weighted Cox proportional hazards model was used to compare the TTD between cohorts. Of the 2509 patients included in the analysis, 89.6% received ibrutinib, and 14.1% received acalabrutinib. TTD was not significantly different between cohorts in the unweighted analysis. After weighting, the cohorts were balanced on all baseline characteristics except cardiovascular risk factors and baseline medications use. The median (95% confidence interval [CI]) TTD was not reached (NR; 95% CI, 25.1 to NR) for the acalabrutinib cohort and was 23.4 months (95% CI, 18.1-28.7) for the ibrutinib cohort. The discontinuation rate at 12 months was 22% for the weighted acalabrutinib cohort vs 31% for the weighted ibrutinib cohort (P = .005). After additional adjustment for prior BTKi use, the acalabrutinib cohort had a 41% lower risk of discontinuation vs ibrutinib (hazard ratio, 0.59; 95% CI, 0.43-0.81; P = .001). In the largest available study comparing BTKis, patients with CLL receiving acalabrutinib demonstrated lower rates of discontinuation and a prolonged time to discontinuation vs those receiving ibrutinib.

Time and personnel costs associated with adverse event (AE) management among patients with chronic lymphocytic leukemia (CLL).

OBJECTIVES: Novel therapies improve clinical outcomes in chronic lymphocytic leukemia (CLL), although adverse event (AE) profiles differ. This study evaluated time and personnel costs of AE management among healthcare professionals (HCPs) treating patients with CLL with novel therapies. METHODS: A non-interventional prospective survey was conducted over 2 months. Eligible HCPs reported the time per day spent performing AE management activities for CLL patients treated with acalabrutinib, ibrutinib, or venetoclax. Mean time and personnel costs (USD) per activity were summarized and used to estimate the total annual costs of AE management for an average-sized oncology practice. RESULTS: For an average-sized practice (28 HCPs with an average of 56 CLL patients), the mean annual personnel cost of AE management for CLL patients on novel agents was estimated at $115,733. The personnel cost associated with acalabrutinib ($20,912) was less than half that of ibrutinib ($53,801) and venetoclax ($41,884), potentially due to fewer severe AEs and less time spent by oncologists managing AEs compared to other HCP types. CONCLUSION: The substantial burden of AE management for patients with CLL may vary by treatment used. Acalabrutinib was associated with lower annual costs of AE management at an oncology practice level compared to ibrutinib and venetoclax.

Effect of ambiguous hemochromatosis gene test results on physician utilization.

BACKGROUND: Genetic test results may be available to greater numbers of people through genetic screening projects and other means. The effects of widespread genetic testing and notification of genetic test results, particularly added costs through increased physician utilization, have not been clearly established. METHODS: A primary care-based cohort of 20,306 participants (Hemochromatosis and Iron Overload Study, Ontario site) were tested for the C282Y and H63D mutations of the HFE gene and for abnormal serum ferritin (SF) and transferrin saturation levels. The primary outcome variable was the total number of physician claims per patient after genetic test notification by mail. Multiple Poisson regression was used to adjust for age, sex, baseline SF, diagnoses of arthritis, diabetes, heart failure and impotence, self-rated health, and the number of claims during the 12 months before notification of results. The reference group had no HFE mutations (wild type) and normal transferrin saturation/SF values. RESULTS: Participants with an ambiguous hemochromatosis gene test and normal iron levels had statistically significantly higher average physician utilization of 3.0%. Participants with HFE mutations (excluding C282Y homozygotes) and elevated iron values showed a 6% increase in physician utilization. CONCLUSIONS: The health effects, if any, of increased utilization in heterozygotes or those with mild ferritin elevations are unknown but are unlikely to be large at the population level. Ambiguous genetic test results are associated with increased physician service use and should be considered when assessing the complete societal costs of widespread genetic testing.

Trends in the incidence and outcomes of heart failure in Ontario, Canada: 1997 to 2007.

BACKGROUND: Heart failure is a leading cause of admission to hospital, but whether the incidence of heart failure is increasing or decreasing is uncertain. We examined temporal trends in the incidence and outcomes of heart failure in Ontario, Canada. METHODS: Using population-based administrative databases of hospital discharge abstracts and physician health insurance claims, we identified 419 551 incident cases of heart failure in Ontario between Apr. 1, 1997, and Mar. 31, 2008. All patients were classified as either inpatients or outpatients based on the patient's location at the time of the initial diagnosis. We tracked subsequent outcomes through linked administrative databases. RESULTS: The age- and sex-standardized incidence of heart failure decreased 32.7% from 454.7 per 100 000 people in 1997 to 306.1 per 100 000 people in 2007 (p < 0.001). A comparable decrease in incidence occurred in both inpatient and outpatient settings. The greatest relative decrease occurred in patients aged 85 and over. Over the study period, 1-year risk-adjusted mortality decreased from 17.7% in 1997 to 16.2% in 2007 (p = 0.02) for outpatients, with a nonsignificant decrease from 35.7% in 1997 to 33.8% in 2007 (p = 0.1) for inpatients. INTERPRETATION: The incidence of heart failure decreased substantially during the study period. Nevertheless, the prognosis for patients with heart failure remains poor and is associated with high mortality.

Determinants of variations in coronary revascularization practices.

BACKGROUND: The ratio of percutaneous coronary interventions to coronary artery bypass graft surgeries (PCI:CABG ratio) varies considerably across hospitals. We conducted a comprehensive study to identify clinical and nonclinical factors associated with variations in the ratio across 17 cardiac centres in the province of Ontario. METHODS: In this retrospective cohort study, we selected a population-based sample of 8972 patients who underwent an index cardiac catheterization between April 2006 and March 2007 at any of 17 hospitals that perform invasive cardiac procedures in the province. We classified the hospitals into four groups by PCI:CABG ratio (low [< 2.0], low-medium [2.0-2.7], medium-high [2.8-3.2] and high [> 3.2]). We explored the relative contribution of patient, physician and hospital factors to variations in the likelihood of patients receiving PCI or CABG surgery within 90 days after the index catheterization. RESULTS: The mean PCI:CABG ratio was 2.7 overall. We observed a threefold variation in the ratios across the four hospital ratio groups, from a mean of 1.6 in the lowest ratio group to a mean of 4.6 in the highest ratio group. Patients with single-vessel disease usually received PCI (88.4%-99.0%) and those with left main artery disease usually underwent CABG (80.8%-94.2%), regardless of the hospital's procedure ratio. Variation in the management of patients with non-emergent multivessel disease accounted for most of the variation in the ratios across hospitals. The mode of revascularization largely reflected the recommendation of the physician performing the diagnostic catheterization and was also influenced by the revascularization "culture" at the treating hospital. INTERPRETATION: The physician performing the diagnostic catheterization and the treating hospital were strong independent predictors of the mode of revascularization. Opportunities exist to improve transparency and consistency around the decision-making process for coronary revascularization, most notably among patients with non-emergent multivessel disease.

Real-world patient characteristics associated with survival of 2 years or more after radium-223 treatment for metastatic castration-resistant prostate cancer (EPIX study).

BACKGROUND: The real-world EPIX study was conducted to gather information about the characteristics of patients with metastatic castration-resistant prostate cancer (mCRPC) who survived ≥2 years after treatment with the alpha-emitter radium-223. METHODS: This retrospective study of electronic health records in the US Flatiron database (NCT04516161) included patients with mCRPC treated with radium-223 between January 2013 and June 2019. Median overall survival (OS) and prostate-specific antigen (PSA) response (≥50% reduction) from start of radium-223 treatment were the primary and secondary endpoints, respectively. Patient characteristics were compared between those who survived ≥2 years versus <2 years, including a subgroup who survived <6 months. RESULTS: In the 1180 patients identified, median OS was 12.9 months (95% CI: 12.1-13.7), and 13% of patients with data at 6 months had a PSA response. The survival groups included 775 patients (65.7%) who survived <2 years (including 264 (22.4%) who survived <6 months) and 185 patients (15.7%) who survived ≥2 years; 220 patients (18.6%) had incomplete follow-up data and were censored. On multivariate analysis, age >75 years, Eastern Cooperative Oncology Group performance status (ECOG PS) 2-4, visceral metastases, prior symptomatic skeletal events (SSEs), and prior chemotherapy were independently prognostic of reduced OS. For patients with survival ≥2 years versus <2 years, median age was 71 versus 75 years, 4% versus 14% had ECOG PS 2-4, 4% versus 10% had visceral metastases, 38% versus 44% had prior SSEs, and 16% versus 32% had prior chemotherapy. CONCLUSIONS: In this study of men with mCRPC treated in real-world clinical practice, median OS was consistent with that seen in the phase 3 ALSYMPCA trial. Patients who survived ≥2 years after the start of radium-223 were younger and had better ECOG PS, lower disease burden, and less use of prior chemotherapy than those who survived <2 years.

Temporal trends in the use of percutaneous coronary intervention and coronary artery bypass surgery in New York State and Ontario.

BACKGROUND: Healthcare reform initiatives in the United States have rekindled debate about the role of government regulation in the healthcare system. Although New York State (NYS) historically has had twice as many coronary revascularizations performed as Ontario, the relative evolution of coronary revascularization patterns in both jurisdictions over time is unknown. METHODS AND RESULTS: We conducted an observational study comparing the temporal trends of cardiac invasive procedures use in NYS and Ontario using population-based data from 1997 to 2006 stratified by procedure indication. For nonacute myocardial infarction patients, the age- and sex-adjusted rate of percutaneous coronary intervention (PCI) was 2.3 times (95% confidence interval, 2.2 to 2.5) greater in NYS than in Ontario in 2004 to 2006. In contrast, population-based rates of coronary artery bypass grafting among nonacute myocardial infarction patients were not significantly different. For acute myocardial infarction patients, differences in coronary revascularization rates between NYS and Ontario narrowed substantially over time. In 2004 to 2006, the relative ratio was 1.3 times higher for PCI (95% confidence interval, 1.2 to 1.5) and 1.4 times higher (95% confidence interval, 1.1 to 1.8) for coronary artery bypass grafting in NYS relative to Ontario. However, a larger relative gap (relative ratio, 2.0; 95% confidence interval, 1.7 to 2.3) was observed among acute myocardial infarction patients undergoing emergency PCIs in NYS compared with Ontario. CONCLUSIONS: The market-oriented financing approach in NYS is associated with markedly higher rates of PCI procedures for both discretionary indications (eg, PCI in nonacute myocardial infarction patients) and emergent indications (eg, primary PCI) compared with the government-funded single-payer system in Ontario.