Healthcare resource utilization following ustekinumab initiation among bio-naïve Canadian patients with moderately-to-severely active Crohn's disease.

BACKGROUND/AIMS: Real-world healthcare resource utilization (HCRU) of bio-naïve patients with Crohn's disease (CD) receiving ustekinumab was assessed. METHODS: A multicentre, retrospective chart review study of bio-naïve Canadian adult patients with moderately-to-severely active CD treated with ustekinumab was conducted. CD-related HCRU (i.e., surgery, hospitalization, or emergency room [ER] visits) was evaluated at Months 4, 6, and 12 post-ustekinumab initiation, and associated costs were sourced from a provincial database. Proportion of patients with HCRU events and ustekinumab persistence were summarized at each timepoint. Paired analysis compared HCRU events and associated costs incurred by the same patient whilst in remission vs. when not in remission. RESULTS: By Month 12, 11.1 % (17/153) of patients had record(s) of any CD-related HCRU event, with ER visits being the most common (7.7 %; 12/155). Hospitalization had the highest average cost (CAD $436.10; SD $2,089.25) across all patients, accounting for 82.2 % of the mean total annual cost/patient (CAD $530.47; SD $2,229.92). While in remission, ≤5 % of patients experienced some healthcare encounter, compared with 7 % when not in remission (P = 0.289). Finally, 93.5 % of patients persisted on ustekinumab at Month 12. CONCLUSIONS: HCRU rates and associated total annual costs were lower for bio-naïve CD patients receiving ustekinumab, and when patients were in remission. Most patients continued with ustekinumab at Month 12.

Real-world effectiveness and safety of ustekinumab in bio-naive patients with moderate-to-severe Crohn's disease: A Canadian multi-center study.

BACKGROUND: Clinical practice guidelines recommend ustekinumab as a first-line biological treatment option for moderately-to-severely active Crohn's disease (CD). However, there is limited real-world effectiveness and safety data in bio-naïve patients. AIMS: To assess ustekinumab effectiveness and safety in bio-naïve CD patients. METHODS: Medical charts were reviewed retrospectively at seven Canadian centers. The primary outcome was the proportion of patients achieving clinical remission at Month 6 following ustekinumab initiation. Secondary outcomes included clinical, biochemical, and endoscopic response, and remission at Months 4, 6 and 12. Ustekinumab safety was assessed over the one-year follow-up period. RESULTS: 158 charts were reviewed. Clinical remission was achieved by 50.0% (36/72), 67.7% (105/155), and 73.7% (84/114) of patients at Months 4, 6, and 12, respectively. At these study timepoints, biochemical remission was observed in 65.2% (43/66), 71.6% (63/88), and 73.9% (68/92) of patients. At Months 6 and 12, endoscopic remission was observed in 40.5% (15/37) and 56.3% (27/48) of patients, respectively. Most participants (93.5%; 145/155) persisted on ustekinumab through Month 12. No serious adverse drug reactions were reported. CONCLUSION: In this real-world study, ustekinumab presents as an effective first-line biologic for induction and maintenance of remission among bio-naïve Canadian patients with moderately-to-severely active CD.

Real-World Safety and Effectiveness of a Bevacizumab Biosimilar (ABP 215) in Metastatic Colorectal Cancer Patients in Canada.

BACKGROUND: ABP 215 is a biosimilar to the reference product, bevacizumab, and was one of the first biosimilars approved by Health Canada for the first-line treatment of metastatic colorectal cancer (mCRC). This study aimed to address gaps in real-world evidence (RWE) including patient characteristics, treatment safety (primary objective), and effectiveness (secondary objective) for first-line ABP 215 therapy in Canadian patients with mCRC. MATERIALS AND METHODS: Retrospective data were collected in 2 waves, at least 1 year (Wave 1) or 2 years (Wave 2) after commercial availability of ABP 215 at each participating site. RESULTS: A total of 75 patients from Wave 1 and 164 patients from Wave 2 treated with a minimum of 1 cycle of ABP 215 were included. At least one safety event of interest (EOI) was recorded for 34.7% of Wave 1 and 42.7% of Wave 2 patients. The median progression free survival (PFS) for Wave 1 and 2 patients were 9.47 (95% confidence interval [CI]: 6.71, 11.90) and 21.38 (95% CI: 15.82, not estimable) months, respectively. Median overall survival was not estimable for Wave 1 and was 26.45 months for Wave 2. CONCLUSION: The safety and effectiveness of ABP 215 observed in this real-world study were comparable to clinical trial findings and to other RWE with longer PFS in the current study.

Estimating the Associated Burden of Illness and Healthcare Utilization of Newly Diagnosed Patients Aged ≥65 with Mantle Cell Lymphoma (MCL) in Ontario, Canada.

BACKGROUND: With the emergence of therapies for mantle cell lymphoma (MCL), understanding the treatment patterns and burden of illness among older patients with MCL in Canada is essential to inform decision making. METHODS: A retrospective study using administrative data matched individuals aged ≥65 who were newly diagnosed with MCL between 1 January 2013 and 31 December 2016 with general population controls. Cases were followed for up to 3 years in order to assess healthcare resource utilization (HCRU), healthcare costs, time to next treatment or death (TTNTD), and overall survival (OS); all were stratified according to first-line treatment. RESULTS: This study matched 159 MCL patients to 636 controls. Direct healthcare costs were highest among MCL patients in the first year following diagnosis (Y1: CAD 77,555 ± 40,789), decreased subsequently (Y2: CAD 40,093 ± 28,720; Y3: CAD 36,059 ± 36,303), and were consistently higher than the costs for controls. The 3-year OS after MCL diagnosis was 68.6%, with patients receiving bendamustine + rituximab (BR) experiencing a significantly higher OS compared to patients treated with other regimens (72.4% vs. 55.6%, p = 0.041). Approximately 40.9% of MCL patients initiated a second-line therapy or died within 3 years. CONCLUSION: Newly diagnosed MCL presents a substantial burden to the healthcare system, with almost half of all patients progressing to a second-line therapy or death within 3 years.

Estimating the Burden of Illness of Relapsed Follicular Lymphoma and Marginal Zone Lymphoma in Ontario, Canada.

BACKGROUND: Many patients with advanced follicular lymphoma (FL) and marginal zone lymphoma (MZL) relapse after first-line chemotherapy. OBJECTIVE: To examine healthcare resource utilization (HCRU) and cost, treatment patterns, progression, and survival of patients with FL and MZL who relapse after first-line treatment, in Ontario, Canada. METHODS: A retrospective, administrative data study identified patients with relapsed FL and MZL (1 January 2005-31 December 2018). Patients were followed for up to three years post relapse to assess HCRU, healthcare costs, time to next treatment (TTNT), and overall survival (OS), stratified by first- and second-line treatment. RESULTS: The study identified 285 FL and 68 MZL cases who relapsed after first-line treatment. Average duration of first-line treatment was 12.4 and 13.4 months for FL and MZL patients, respectively. Drug (35.9%) and cancer clinic costs (28.1%) were major contributors to higher costs in year 1. Three-year OS was 83.9% after FL and 74.2% after MZL relapse. No statistically significant differences were observed in TTNT and OS between patients with FL who received R-CHOP/R-CVP/BR in the first line only versus both the first- and second- line. A total of 31% of FL and 34% of MZL patients progressed to third-line treatment within three years of initial relapse. CONCLUSION: Relapsing and remitting nature of FL and MZL in a subset of patients results in substantial burden to patients and the healthcare system.

Associations between clinical pathway concordance, cost, and survival outcomes for stage II colon cancer: a population-based study.

This study measures patient's concordance between clinical reference pathways with survival or cost among a population-based cohort of colon cancer patients applying a continuous measure of concordance. The primary hypothesis is that a higher concordance score with the clinical pathway is significantly associated with longer survival or lower cost. The study informs whether patient's adherence to a defined clinical pathway is beneficial to patients' outcomes or health system. An externally determined clinical pathway for colon cancer was used to identify treatment nodes in colon cancer care. Using observational data up to 2019, the study generated a continuous measure of pathway concordance. The study measured whether incremental improvements in pathway concordance were associated with survival and treatment costs. Concordance between patients' reference pathways and their observed trajectories of care was highly statistically associated with survivorship [hazard ratio: 0.95 (95% confidence interval, CI, 0.95-0.96)], showing that adherence to the clinical pathway was associated with a lower mortality rate. An increase in concordance was statistically significantly associated with a decrease in health system cost. When patients' care followed the clinical pathway, survival outcomes were better and total health system costs were lower in this cohort. This finding creates a compelling case for further research into understanding the barriers to pathway concordance and developing interventions to improve outcomes and help providers implement best practice care where appropriate.

Identifying Breast Cancer Recurrence in Administrative Data: Algorithm Development and Validation.

Breast cancer recurrence is an important outcome for patients and healthcare systems, but it is not routinely reported in cancer registries. We developed an algorithm to identify patients who experienced recurrence or a second case of primary breast cancer (combined as a "second breast cancer event") using administrative data from the population of Ontario, Canada. A retrospective cohort study design was used including patients diagnosed with stage 0-III breast cancer in the Ontario Cancer Registry between 1 January 2009 and 31 December 2012 and alive six months post-diagnosis. We applied the algorithm to healthcare utilization data from six months post-diagnosis until death or 31 December 2013, whichever came first. We validated the algorithm's diagnostic accuracy against a manual patient record review (n = 2245 patients). The algorithm had a sensitivity of 85%, a specificity of 94%, a positive predictive value of 67%, a negative predictive value of 98%, an accuracy of 93%, a kappa value of 71%, and a prevalence-adjusted bias-adjusted kappa value of 85%. The second breast cancer event rate was 16.5% according to the algorithm and 13.0% according to manual review. Our algorithm's performance was comparable to previously published algorithms and is sufficient for healthcare system monitoring. Administrative data from a population can, therefore, be interpreted using new methods to identify new outcome measures.

Development of population-level colon cancer pathway concordance measures and association with survival.

Clinical cancer pathways help standardize healthcare delivery to optimize patient outcomes and health system costs. However, population-level measurement of concordance between standardized pathways and actual care received is lacking. Two measures of pathway concordance were developed for a simplified colon cancer pathway map for Stage II-III colon cancer patients in Ontario, Canada: a cumulative count of concordant events (CCCE) and the Levenshtein algorithm. Associations of concordance with patient survival were estimated using Cox proportional hazards models adjusted for patient characteristics and time-dependent cancer-related activities. Models were compared and the impact of including concordance scores was quantified using the likelihood ratio chi-squared test. The ability of the measures to discriminate between survivors and decedents was compared using the C-index. Normalized concordance scores were significantly associated with patient survival in models for cancer stage-a 10% increase in concordance for Stage II patients resulted in a CCCE score adjusted hazard ratio (aHR) of death of 0.93, 95% CI 0.88-0.98 and a Levenshtein score aHR of 0.64, 95% CI 0.60-0.67. A similar relationship was found for Stage III patients-a 10% increase in concordance resulted in a CCCE aHR of 0.85, 95% CI 0.81-0.88 and a Levenshtein aHR of 0.78, 95% CI, 0.74-0.81. Pathway concordance can be used as a tool for health systems to monitor deviations from established clinical pathways. The Levenshtein score better characterized differences between actual care and clinical pathways in a population, was more strongly associated with survival and demonstrated better patient discrimination.

Clearing the surgical backlog caused by COVID-19 in Ontario: a time series modelling study.

BACKGROUND: To mitigate the effects of coronavirus disease 2019 (COVID-19), jurisdictions worldwide ramped down nonemergent surgeries, creating a global surgical backlog. We sought to estimate the size of the nonemergent surgical backlog during COVID-19 in Ontario, Canada, and the time and resources required to clear the backlog. METHODS: We used 6 Ontario or Canadian population administrative sources to obtain data covering part or all of the period between Jan. 1, 2017, and June 13, 2020, on historical volumes and operating room throughput distributions by surgery type and region, and lengths of stay in ward and intensive care unit (ICU) beds. We used time series forecasting, queuing models and probabilistic sensitivity analysis to estimate the size of the backlog and clearance time for a +10% (+1 day per week at 50% capacity) surge scenario. RESULTS: Between Mar. 15 and June 13, 2020, the estimated backlog in Ontario was 148 364 surgeries (95% prediction interval 124 508-174 589), an average weekly increase of 11 413 surgeries. Estimated backlog clearance time is 84 weeks (95% confidence interval [CI] 46-145), with an estimated weekly throughput of 717 patients (95% CI 326-1367) requiring 719 operating room hours (95% CI 431-1038), 265 ward beds (95% CI 87-678) and 9 ICU beds (95% CI 4-20) per week. INTERPRETATION: The magnitude of the surgical backlog from COVID-19 raises serious implications for the recovery phase in Ontario. Our framework for modelling surgical backlog recovery can be adapted to other jurisdictions, using local data to assist with planning.

Estimation of high-dimensional propensity scores with multiple exposure levels.

PURPOSE: Little information is available on the performance of high-dimensional propensity scores (HDPS) in settings with more than two exposure levels. Our objective was to adapt the HDPS algorithm to allow for the inclusion of multilevel treatments and compare estimates obtained via this approach with those obtained via pairwise comparisons in a case study using real-world data. METHODS: We conducted a retrospective cohort study of cardiovascular events associated with three smoking cessation drugs (varenicline, bupropion, nicotine replacement therapy [NRT]) using the Clinical Practice Research Datalink. We applied the binary HDPS algorithm adjusted for pre-specified and empirically-selected covariates to cohorts formed by each treatment pair. We then constructed multinomial HDPS models on a cohort of new users of any of the three drugs, adjusting for predefined covariates and different combinations of empirically-selected covariates. After trimming the area of non-overlap of the HDPS distributions, the effects of the study drugs on cardiovascular events were estimated with the Cox proportional hazards models adjusted for propensity score category. RESULTS: Outcome models adjusted for multinomial HDPS estimated treatment effects that were slightly more protective than those estimated in pairwise comparisons (varenicline vs NRT: HRMultinomial = 0.60-0.62, HRPairwise = 0.64; bupropion vs NRT: HRMultinomial = 0.70-0.72, HRPairwise = 0.76). Trimming rates were similar between the two approaches. CONCLUSIONS: The extension of HDPS to multilevel exposures is a valid and practical approach to confounder control that may be useful when comparing different classes of drugs prescribed for the same indication or different molecules within a given drug class.

Ambulatory Toxicity Management (AToM) Pilot: results of a pilot study of a pro-active, telephone-based intervention to improve toxicity management during chemotherapy for breast cancer.

BACKGROUND: Chemotherapy is associated with a significant risk of toxicity, which often peaks between ambulatory visits to the cancer centre. Remote symptom management support is a tool to optimize self-management and healthcare utilization, including emergency department visits and hospitalizations (ED+H) during chemotherapy. We performed a single-arm pilot study to evaluate the feasibility, acceptability, and potential impact of a telephone symptom management intervention on healthcare utilization during chemotherapy for early stage breast cancer (EBC). METHODS: Women starting adjuvant or neoadjuvant chemotherapy for EBC at two cancer centres in Ontario, Canada, received standardized, nurse-led calls to assess common toxicities at two time points following each chemotherapy administration. Feasibility outcomes included patient enrollment, retention, RN adherence to delivering calls per the study schedule, and resource use associated with calls; acceptability was evaluated based on patient and provider feedback. Impact on acute care utilization was evaluated post hoc by linking individual patient records to provincial data holdings to examine ED+H patterns among participating patients compared to contemporaneous controls. RESULTS: Between September 2013 and December 2014, 77 women were enrolled (mean age 55 years). Most commonly used regimens were AC-paclitaxel (58%) and FEC-docetaxel (16%); 78% of patients received primary granulocyte colony-stimulating factor prophylaxis. 83.8% of calls were delivered per schedule; mean call duration was 9 min. The intervention was well received by both patients and clinicians. Comparison of ED+H rates among study participants versus controls showed that there were fewer ED visits in intervention patients [incidence rate ratio (IRR) (95% CI) = 0.54 (0.36, 0.81)] but no difference in the rate of hospitalizations [IRR (95% CI) = 1.02 (0.59, 1.77)]. Main implementation challenges included identifying eligible patients, fitting the calls into existing clinical responsibilities, and effective communication to the patient's clinical team. CONCLUSIONS: Telephone-based pro-active toxicity management during chemotherapy is feasible, perceived as valuable by clinicians and patients, and may be associated with lower rates of acute care use. However, attention must be paid to workflow issues for scalability. Larger scale evaluation of this approach is in progress.

Population-based outcomes of men with a single negative prostate biopsy: Importance of continued follow-up among older patients.

PURPOSE: To determine in Ontario-based men with a single negative transrectal ultrasound-guided prostate biopsy the long-term rates of prostate cancer-specific mortality, diagnosis, and treatment; number of repeat biopsies; and predictors of prostate cancer diagnosis and mortality. MATERIALS AND METHODS: This was a population-based cohort study, using data from linked, validated health administrative databases, of all Ontario-based men with a negative first biopsy between January 1994 and October 2014. Patients were followed from time of first biopsy till death, administrative censoring, or end of study period. Cumulative incidence functions were used to calculate the study outcomes' cumulative incidences. Univariable and multivariable regression analyses using Fine and Gray's semiparametric proportional hazards model were used to assess predictors of prostate cancer diagnosis and mortality. RESULTS: The study cohort included 95,675 men with a median age of 63.0years. Median follow-up was 8.1years. The 20-year cumulative rates of prostate cancer-specific mortality and diagnosis were 1.8% and 23.7%, respectively. Men ages 70 to 79 and 80 to 84 at initial biopsy had 20-year prostate cancer-specific mortality cumulative rates of 3.2% and 6.4% respectively. The 20-year cumulative rate of receiving radical prostatectomy was 7.6%. Higher socioeconomic status and urban residence were associated with higher diagnosis risks yet lower prostate cancer-specific mortality risks. CONCLUSIONS: This is the first population-based study assessing long-term cancer outcomes in North American men with a single negative transrectal ultrasound-guided prostate biopsy. Following a negative initial biopsy, 23.7% of men are still diagnosed with and 1.8% die of prostate cancer within 20years. Cancer-specific mortality outcomes are significantly worse in older men, with prostate cancer mortality rates several times higher than the rest of the population.

Effect of PET/CT on the Management and Outcomes of Participants with Hodgkin and Aggressive Non-Hodgkin Lymphoma: A Multicenter Registry.

Purpose To determine the relationship of PET/CT staging to the management and outcomes of participants with apparent limited-stage (LS) Hodgkin lymphoma (HL) or aggressive non-HL (ANHL) treated with curative intent. Materials and Methods This prospective multicenter registry included 850 participants (467 men and 383 women; median age, 54.1 years) from nine centers who had LS HL or ANHL on the basis of clinical data and CT, or with equivocal CT for advanced stage, who were considered for curative-intent first-line therapy. Participants were recruited between May 1, 2013, and December 31, 2015. Pre-PET/CT treatment plan was compared with treatment provided. Survival and second-line therapy initiation were compared with an historical control pool staged by using CT alone. Administrative data sources were used to control for baseline characteristics. Outcomes were assessed by using adjusted Cox proportional hazards regression and propensity score matching. Results PET/CT helped to upstage 150 of 850 participants (17.6%). There was a change in planned therapy in 224 of 580 (38.6%) of participants after PET/CT. There was a lower 1-year mortality for participants with ANHL in the PET/CT versus CT cohort (hazard ratio, 0.63; 95% confidence interval: 0.40, 1.0; P < .05) and for those with LS at PET/CT compared with those with LS at CT (hazard ratio, 0.40; 95% confidence interval: 0.21, 0.74; P = .004). For participants with HL, no 1-year outcome difference was found (P = .16). Conclusion PET/CT helped to upstage approximately 18% of participants and planned management was frequently altered. Participants with aggressive non-Hodgkin lymphoma whose first-line therapy was guided by PET/CT had significantly better survival compared with participants whose treatment was guided by CT. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Scott in this issue.

Population-Based Study on Patterns of Cardiac Stress Testing After Percutaneous Coronary Intervention.

BACKGROUND: The appropriate use criteria considers cardiac stress testing within 2 years after percutaneous coronary intervention (PCI) to be rarely appropriate, unless prompted by symptoms or change in clinical status. Little is known about the patterns of cardiac stress testing after PCI in the single-payer Canadian healthcare system, where mechanisms for reimbursement are different from the United States. METHODS AND RESULTS: Frequency and timing of cardiac stress testing within 2 years of PCI performed between April 2004 and March 2013 in Ontario, Canada, was determined from linked provincial databases. Subsequent rates of coronary angiography and revascularization after stress testing were ascertained. Of the 112 691 patients with PCI, 67 442 (59.8%) underwent at least 1 stress test, with 38 267 (34.0%) undergoing repeat stress testing (ie, >1 stress test) within 2 years. Patients who underwent stress testing were younger, had less medical comorbidities, were more likely to reside in urban areas, and had higher incomes. Spikes in incidence of repeat stress testing were observed at 3 to 4 months, 6 to 7 months, and 12 to 13 months after the prior stress test. Of those tested, only 5.9% underwent subsequent coronary angiography, and only 3.1% underwent repeat revascularization within 60 days of stress testing. CONCLUSIONS: More than half of all patients undergo cardiac stress testing within 2 years of PCI, with one third undergoing repeat stress tests. Only 1 of 30 tested patients underwent repeat revascularization. These findings reinforce the appropriate use criteria recommendations against routine stress testing after PCI. Further work is needed to aid with the selection of patients most likely to benefit from stress testing after PCI.

Efficacy and Safety of Smoking Cessation Interventions in Patients With Cardiovascular Disease: A Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Although the efficacy and safety of smoking cessation interventions are well established, their efficacy and safety in patients with cardiovascular disease (CVD) remain unclear. The objective of this study was to evaluate the efficacy and safety of pharmacological and behavioral smoking cessation interventions in CVD patients via a meta-analysis of randomized controlled trials. METHODS AND RESULTS: EMBASE, PsycINFO, MEDLINE, PubMed, and the Cochrane Tobacco Addiction Specialized Register were searched for randomized controlled trials evaluating the efficacy of smoking cessation pharmacotherapies and behavioral therapies in CVD patients. Outcomes of interest were smoking abstinence at 6 and 12 months, defined using the most rigorous criteria reported. Data were pooled across studies for direct comparisons using random-effects models. Network meta-analysis using a graph-theoretical approach was used to generate the indirect comparisons. Seven pharmacotherapy randomized controlled trials (n=2809) and 17 behavioral intervention randomized controlled trials (n=4666) met our inclusion criteria. Our network meta-analysis revealed that varenicline (relative risk [RR]: 2.64; 95% confidence interval [CI], 1.34-5.21) and bupropion (RR: 1.42; 95% CI, 1.01-2.01) were associated with greater abstinence than placebo. The evidence about nicotine replacement therapies was inconclusive (RR: 1.22; 95% CI, 0.72-2.06). Telephone therapy (RR: 1.47; 95% CI: 1.15-1.88) and individual counseling (RR: 1.64, 95% CI: 1.17-2.28) were both more efficacious than usual care, whereas in-hospital behavioral interventions were not (RR: 1.05; 95% CI, 0.78-1.43). CONCLUSIONS: Our meta-analysis suggests varenicline and bupropion, as well as individual and telephone counseling, are efficacious for smoking cessation in CVD patients.

Statin potency and the risk of hospitalization for community-acquired pneumonia.

AIM: Previous studies suggest that statins may have beneficial respiratory effects. However, it is unclear if these purported benefits vary with statin potency. Our objective was to determine if higher potency statins, compared with lower potency statins, were associated with a reduced risk of hospitalization for community-acquired pneumonia (HCAP). METHODS: We conducted a nested case-control analysis of a retrospective, population-based cohort of new users of statins using data extracted from the UK's Clinical Practice Research Datalink and Hospital Episode Statistics. For each HCAP case, we used risk set sampling to randomly select up to 10 controls, matched on sex, age, cohort entry date and follow-up duration. We used conditional logistic regression with high-dimensional propensity scores to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for HCAP with current use of higher potency statin vs. lower potency statins. RESULTS: A total of 217 721 patients entered the cohort on a lower potency statin and 130 707 entered on a higher potency statin; these patients resulted in 2251 cases of HCAP during 561 886 person-years of observation (rate: 4.0 HCAP per 1000 persons per year, 95% CI: 3.8-4.2). The analysis included 22 178 matched controls. Compared with lower potency statins, higher potency statins were associated with an increased rate of HCAP (HR: 1.14, 95% CI: 1.03-1.27). Higher potency statins were also associated with an increased rate of fatal HCAP (HR: 1.29, 95% CI: 1.04-1.59). CONCLUSIONS: Higher potency statins were not associated with a decreased risk of HCAP compared with lower potency statins.

5α-Reductase Inhibitors and the Risk of Cancer-Related Mortality in Men With Prostate Cancer.

IMPORTANCE: 5α-Reductase inhibitors (5-ARIs) are widely used in the treatment of benign prostatic hyperplasia. However, randomized clinical trials have raised concerns that their use may be associated with an increased risk of high-grade prostate cancer tumors that would ultimately lead to worse prostate cancer outcomes. To date, few observational studies have addressed this important safety concern. OBJECTIVE: To determine whether the use of 5-ARIs before prostate cancer diagnosis is associated with an increased risk of cancer-specific and all-cause mortality in men with a new diagnosis of prostate cancer in the real-world setting. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted in a cohort of 13,892 men with a new diagnosis of prostate cancer between January 1, 1999, and December 31, 2009, who were followed up until October 1, 2012. Patients were individually linked across 4 databases from the United Kingdom: National Cancer Data Repository, Clinical Practice Research Datalink, Hospital Episodes Statistics database, and Office for National Statistics database. MAIN OUTCOMES AND MEASURES: Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% CIs of prostate cancer-specific and all-cause mortality associated with prediagnostic use of 5-ARIs. For each outcome, 2 models were constructed, one adjusted for predefined covariates (conventional model) and another adjusted for high-dimensional propensity score (HD-PS) deciles. RESULTS: During a mean (SD) of 4.5 (3.1) years, 5001 deaths occurred, including 2429 from prostate cancer (crude incidence rate of 3.86 per 100 person-years [95% CI, 3.71-4.02]). In the conventional model, use of 5-ARIs before prostate cancer diagnosis was not associated with an increased risk of prostate cancer-specific mortality (crude incidence rates, 3.76 [95% CI, 3.04-4.59] [use] vs 3.87 [95% CI, 3.71-4.03] [nonuse] per 100 person-years; adjusted hazard ratio [aHR], 0.86 [95% CI, 0.69-1.06]) and all-cause mortality (crude incidence rates, 8.42 [95% CI, 7.32-9.64] [use] vs 7.93 [95% CI, 7.71-8.16] [nonuse] per 100 person-years; aHR, 0.87; 95% CI, 0.75-1.00). Similar results were observed with the HD-PS adjusted model (prostate cancer-specific mortality: aHR, 0.90 [95% CI, 0.73-1.13]; and all-cause mortality: aHR, 0.92 [95% CI, 0.80-1.07]). CONCLUSIONS AND RELEVANCE: The use of 5-ARIs was not associated with an increased risk of prostate cancer-specific and all-cause mortality in men with a new diagnosis of prostate cancer. While these results provide reassurance, additional studies are needed to replicate these findings.

A meta-analysis of randomized controlled trials of the risk of bleeding with apixaban versus vitamin K antagonists.

Apixaban is one of the new oral anticoagulants, which is prescribed as an alternative to vitamin K antagonists (VKAs). Concerns regarding its bleeding profile persist and require further evaluation. Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) to compare the risks of bleeding and all-cause mortality between apixaban and VKAs. The MEDLINE, EMBASE, and Cochrane Library of Clinical Trials databases were systematically searched for RCTs comparing the risks of bleeding and all-cause mortality of apixaban (2.5 or 5 mg twice daily) with those of VKAs. We included RCTs conducted in adults and published in English or French. Data were pooled across RCTs using random-effects meta-analytical models. Our systematic search identified 5 RCTs meeting our inclusion criteria (n = 24,435). They included patients with atrial fibrillation (n = 18,358), total knee replacement surgery (n = 458), and venous thromboembolism (n = 5,619). Data pooled across RCTs revealed that apixaban was associated with reduced risks of any bleeding (relative risk [RR] 0.73, 95% confidence interval [CI] 0.59 to 0.90) and a composite of major or clinically relevant nonmajor bleeding (RR 0.60, 95% CI 0.40 to 0.88). Apixaban was also associated with a lower risk of intracranial bleeding (RR 0.42, 95% CI 0.31 to 0.58) whereas analyses of major and minor bleeding were inconclusive. Moreover, apixaban was associated with decreased all-cause mortality (RR 0.89, 95% CI 0.81 to 0.99) although this finding was driven by the results of the ARISTOTLE trial. In conclusion, our meta-analysis found that apixaban is associated with a lower risk of bleeding than VKAs, providing some reassurance regarding its safety.

Use of statins and the risk of death in patients with prostate cancer.

PURPOSE: To determine whether the use of statins after prostate cancer diagnosis is associated with a decreased risk of cancer-related mortality and all-cause mortality and to assess whether this association is modified by prediagnostic use of statins. PATIENTS AND METHODS: A cohort of 11,772 men newly diagnosed with nonmetastatic prostate cancer between April 1, 1998, and December 31, 2009, followed until October 1, 2012, was identified using a large population-based electronic database from the United Kingdom. Time-dependent Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 95% CIs of mortality outcomes associated with postdiagnostic use of statins, lagged by 1 year to account for latency considerations and to minimize reverse causality, and considering effect modification by prediagnostic use of statins. RESULTS: During a mean follow-up time of 4.4 years (standard deviation, 2.9 years), 3,499 deaths occurred, including 1,791 from prostate cancer. Postdiagnostic use of statins was associated with a decreased risk of prostate cancer mortality (HR, 0.76; 95% CI, 0.66 to 0.88) and all-cause mortality (HR, 0.86; 95% CI, 0.78 to 0.95). These decreased risks of prostate cancer mortality and all-cause mortality were more pronounced in patients who also used statins before diagnosis (HR, 0.55; 95% CI, 0.41 to 0.74; and HR, 0.66; 95% CI, 0.53 to 0.81, respectively), with weaker effects in patients who initiated the treatment only after diagnosis (HR, 0.82; 95% CI, 0.71 to 0.96; and HR, 0.91; 95% CI, 0.82 to 1.01, respectively). CONCLUSION: Overall, the use of statins after diagnosis was associated with a decreased risk in prostate cancer mortality. However, this effect was stronger in patients who also used statins before diagnosis.