Brief communication: global temporal trends in the efficacy of clarithromycin-based regimens for the treatment of Helicobacter pylori infection.

Background: Helicobacter pylori eradication rates achieved with clarithromycin-based triple therapies are declining due to antibiotic resistance, but data regarding temporal changes in efficacy with these eradication therapies are scarce. Objective: To evaluate the efficacy of clarithromycin-based triple eradication regimens over time. Design: A comprehensive literature review and time-trend analysis. Data sources and methods: Bibliographies of recently published systematic literature reviews were searched and supplemented with a targeted literature review conducted using Medline and Embase databases and ProQuest from conception to May 2021. Studies reporting H. pylori eradication rates of clarithromycin-based triple therapies were included and temporal trends were estimated using a random-effects model. Results: Eradication rates for triple therapies containing proton pump inhibitors (PPIs), clarithromycin, and amoxicillin showed a significant decline over the past 23 years (p = 0.0315). However, this decline was not significant when eradication rates achieved with vonoprazan-based triple therapy were included (p = 0.3910). Conclusion: Vonoprazan-based triple therapy partially mitigated the decline in eradication rates seen with PPI-based triple therapy, likely due to more powerful acid suppression of vonoprazan.

Overall and complete response rates as potential surrogates for overall survival in relapsed/refractory multiple myeloma.

Aim: The correlation between response and survival has not been well-studied in relapsed or refractory multiple myeloma (RRMM). Materials & methods: A systematic literature review of Medline, Embase and Cochrane databases (2010-06/2020) and relevant congresses (2018-2020) was performed to identify randomized clinical trials in RRMM reporting median overall survival (mOS), progression-free survival and response end points. The relationship between mOS and response end points was analyzed using Pearson's product-moment correlation. Results: A total of 81 records for 65 original studies, representing 12,827 patients were included. The correlation was moderate for mOS with overall response rate (Pearson r = 0.79), very good partial response (r = 0.73) and duration of response (r = 0.78); all were statistically significant. In linear regression models, estimated mOS gain was 0.48, 0.47 and 1.94 months per percentage point of overall response rate, very good partial response and complete response, respectively (all p < 0.001). Significance was maintained after adjustment for age, relapsed versus refractory multiple myeloma and study year. The analysis was limited by small sample sizes and inconsistent reporting of study-level covariates. Conclusion: These findings support short-term response-based end points as surrogates to survival in RRMM.

Treatments for multiple myeloma may not work for every patient and the cancer may come back. In clinical trials, it is difficult to find out how well new treatments work in allowing patients to live longer. This is especially true when patients have advanced disease that has returned or has not responded to treatment. How well a patient responds to treatment (i.e., has a decreased extent of disease) could indicate whether the drug will help the patient live longer, but the relationship between response to treatment and survival is not fully understood. We conducted a systematic review and meta-analysis to better understand how response rates and survival are related. A systematic review collects all the published research on a specific subject, and a meta-analysis is a statistical method that creates a single finding from several separate studies. This study found a moderate relationship between how long patients live after receiving treatment for multiple myeloma and their response to treatment. This would allow response-to-treatment data from clinical trials to be used to predict better survival and show the drug can help patients.

Filgotinib Improved Health-Related Quality of Life and Led to Comprehensive Disease Control in Individuals with Ulcerative Colitis: Data from the SELECTION Trial.

BACKGROUND AND AIMS: Ulcerative colitis [UC] impacts patients' health-related quality of life [HRQoL]. We assessed HRQoL and an exploratory patient-level composite endpoint ('Comprehensive Disease Control' [CDC]) in individuals receiving filgotinib [an oral JAK1 preferential inhibitor] in the SELECTION trial. METHODS: In SELECTION [NCT02914522], a double-blind, randomized, placebo-controlled, phase 2b/3 trial, adults with moderately to severely active UC received once-daily filgotinib 200 mg, filgotinib 100 mg or placebo for 11 weeks in Induction Study A [biologic-naïve] or B [biologic-experienced]. Filgotinib responders [week 10 clinical remission/response] were re-randomized to their filgotinib regimen or placebo for the 48-week Maintenance Study. We assessed week 10 and week 58 SF-36, EQ-5D, WPAI and IBDQ scores. Achievement of CDC (patient-level partial Mayo Clinic Score [pMCS] remission [pMCS ≤2, no individual rectal bleeding, stool frequency or physician's global assessment subscore >1], endoscopic improvement [endoscopic subscore ≤1], faecal calprotectin <150 µg/g and IBDQ score ≥170) and its association with HRQoL and histological outcomes were also explored. RESULTS: Analyses included 382 biologic-naïve and 404 biologic-experienced patients. Filgotinib 200 mg induced and maintained improvements vs placebo in SF-36, EQ-5D, WPAI and IBDQ scores, and restored HRQoL by week 10. Proportionally more filgotinib 200 mg- than placebo-treated patients achieved CDC at weeks 10 and 58 [p < 0.01]. CDC was associated with clinically important improvements in HRQoL and histological remission over both periods. CONCLUSIONS: Filgotinib 200 mg results in short- and long-term improvements in HRQoL. High-level improvement of HRQoL relates to a stringent composite endpoint suggesting meaningful disease control in a subset of filgotinib-treated individuals.ClinicalTrials.gov identifier: NCT02914522.

The rs579459 ABO gene polymorphism and risk of incident cardiovascular events in obstructive sleep apnea: a pilot study.

PURPOSE: We have previously shown that the TT genotype (rs579459 location of the ABO gene) is significantly associated with circulating levels of e-selectin in patients with suspected obstructive sleep apnea (OSA). We hypothesized that this genotype would be associated with incident cardiovascular disease (CVD). METHODS: Patients with suspected OSA who had a full diagnostic polysomnogram from 2003 to 2011 were recruited; CV events occurring within 8 years of polysomnography were identified by linkage to provincial health databases. Cox proportional hazards models were used to evaluate the incidence of first CV events as a function of the rs579459 genotype. RESULTS: In this targeted study, 408 patients were studied, and 39 incident events were identified. A larger proportion of patients with the TT genotype had an event (31/247; 12.6%) than the CT and CC genotypes (8/161; 5.0%); in univariate analysis, the TT genotype was significantly associated with CV events (HR = 2.53; 95% CI = 1.16-5.51, p = 0.02). After adjustment for age, AHI, sex, smoking, diabetes, statin use, and BMI, the TT genotype remained a significant predictor (HR = 2.35; 95% CI = 1.02-5.42, p = 0.046). No events were found in patients with an absence of both OSA and the TT genotype (N = 30). The effect of the SNP was partially (16.2%) mediated by e-selectin levels. CONCLUSION: This is the first study to examine genetic variants as a risk factor for incident CVD in the context of OSA. Although these results are preliminary and in need of replication, it suggests that genetic markers may become useful in helping to guide precision clinical care.

One-Year Prospective Follow-up of Women With INOCA and MINOCA at a Canadian Women's Heart Centre.

BACKGROUND: Many women with cardiac chest pain and ischemia or myocardial infarction have no obstructive coronary artery disease (INOCA or MINOCA). Studies suggest that these patients have a decreased quality of life and are at increased risk of cardiovascular events. Our study reports 1-year quality of life, frequency of angina, and outcomes following entry into a multidisciplinary Women's Heart Centre (WHC). METHODS: Patients with INOCA and MINOCA completed questionnaires on baseline demographics and clinical presentation. At 1-year, frequency of chest pain, quality of life, depression and anxiety symptoms, and cardiovascular outcomes were reported and compared with baseline. RESULTS: A total of 154 women with nonobstructive coronary artery disease were included in this study (112 patients with INOCA and 42 with MINOCA). Median age was 59 years, and the most common referral was for chest pain (94% in INOCA and 66% in MINOCA). At baseline, 64% of patients with INOCA and 43% of patients with MINOCA did not have specific diagnoses. Following investigations in the WHC, 71.4% of patients with INOCA established a new or a changed diagnosis (most common was coronary microvascular dysfunction at 68%), whereas 60% of patients with MINOCA established new or changed diagnoses (the most common of which was coronary vasospasm at 60%). At 1-year, participants had significantly decreased chest pain, improved quality of life, and improved mental health. CONCLUSIONS: A multidisciplinary WHC significantly increases the yield of a specific diagnosis in patients with INOCA and MINOCA. Further, attending a WHC could significantly improve the clinical and psychological outcomes of women with INOCA and MINOCA.

Epidemiology, Healthcare Resource Utilization, and Mortality of Asthma and COPD in COVID-19: A Systematic Literature Review and Meta-Analyses.

Purpose: There has been concern that asthma and chronic obstructive pulmonary disease [COPD] increase the risk of developing and exacerbating COVID-19. The effect of medications such as inhaled corticosteroids (ICS) and biologics on COVID-19 is unclear. This systematic literature review analyzed the published evidence on epidemiology and the burden of illness of asthma and COPD, and the use of baseline medicines among COVID-19 populations. Patients and Methods: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, Embase®, MEDLINE® and Cochrane were searched (January 2019-August 2021). The prevalence of asthma or COPD among COVID-19 populations was compared to the country-specific populations. Odds ratios (ORs) were estimated to compare healthcare resource utilization (HCRU) rates, and meta-analyses of outcomes were estimated from age-adjusted ORs (aORs) or hazard ratios (aHRs). Meta-analyses of COVID-19 outcomes were conducted using random effects models for binary outcomes. Results: Given the number and heterogeneity of studies, only 183 high-quality studies were analyzed, which reported hospitalization, intensive care unit (ICU) admissions, ventilation/intubation, or mortality. Asthma patients were not at increased risk for COVID-19-related hospitalization (OR = 1.05, 95% CI: 0.92 to 1.20), ICU admission (OR = 1.21, 95% CI: 0.99 to 1.1.48), ventilation/intubation (OR = 1.24, 95% CI: 0.95 to 1.62), or mortality (OR = 0.85, 95% CI: 0.75 to 0.96). Accounting for confounding variables, COPD patients were at higher risk of hospitalization (aOR = 1.45, 95% CI: 1.30 to 1.61), ICU admission (aOR = 1.28, 95% CI: 1.08 to 1.51), and mortality (aOR = 1.41, 95% CI: 1.37 to 1.65). Sixty-five studies reported outcomes associated with ICS or biologic use. There was limited evidence that ICS or biologics significantly impacted the risk of SARS-CoV-2 infection, HCRU, or mortality in asthma or COPD patients. Conclusion: In high-quality studies included, patients with asthma were not at significantly higher odds for adverse COVID-19-related outcomes, while patients with COPD were at higher odds. There was no clear evidence that baseline medication affected outcomes. Registration: PROSPERO (CRD42021233963).

Response rates and minimal residual disease outcomes as potential surrogates for progression-free survival in newly diagnosed multiple myeloma.

Progression-free survival (PFS) is a common primary endpoint in newly diagnosed multiple myeloma (NDMM). Patients with NDMM typically have longer PFS and are more likely to achieve minimal residual disease (MRD) or complete response (CR) compared to patients with relapsed or refractory multiple myeloma. Response-based surrogate endpoints may hold value given the longer follow-up time required to evaluate PFS in NDMM. In this work, systematic literature reviews of Medline, Embase, and Cochrane databases (2010-06/2020) and relevant congresses (2018-2020) were performed to identify randomized clinical trials (RCTs) and real-world studies in NDMM reporting median PFS and objective response. Associations between PFS and each response endpoint were evaluated using Pearson's product-moment correlation weighted by sample size in each RCT arm. Unadjusted and adjusted weighted linear regression models were applied to estimate the gain in median PFS associated with each response endpoint. Statistically significant correlations were identified for median PFS with overall response rate (ORR; Pearson r = 0.59), CR (r = 0.48), stringent CR (sCR; r = 0.68), and MRD (r = 0.69). The unadjusted models estimated 0.50 (95% CI: 0.36, 0.64; p<0.001), 0.42 (95% CI: 0.25, 0.58; p<0.001), 1.05 (95% CI: 0.58, 1.52; p<0.001), and 0.35 (95% CI: 0.12, 0.58; p = 0.006) months of median PFS gained per point of ORR, CR, sCR, and MRD, respectively. Associations for median PFS remained statistically significant in models adjusted for age and treatment type with ORR (0.35, 95% CI: 0.21, 0.49; p<0.001), and adjusted for age and International Staging System risk stage with CR (0.29, 95% CI: 0.16, 0.41; p<0.001). Due to small sample size, adjusted models could not be constructed for sCR or MRD. Nevertheless, evidence of significant survival benefit (p<0.05) associated with MRD negativity and sCR was identified across real-world studies. These findings provide support for the use of response outcomes as surrogate endpoints to estimate PFS benefit in NDMM.

Symptom subtypes and risk of incident cardiovascular and cerebrovascular disease in a clinic-based obstructive sleep apnea cohort.

STUDY OBJECTIVES: Patients with obstructive sleep apnea (OSA) are at increased risk of cardiovascular and cerebrovascular disease, but predicting those at greatest risk is challenging. Using latent class analysis, patients with OSA can be placed into discrete symptom subtypes. The aim of this study was to determine whether symptom subtypes are associated with future cerebrovascular disease in patients with OSA in a clinic-based cohort. METHODS: Patients with suspected OSA referred for a polysomnogram at an academic sleep center completed a comprehensive symptom survey. Patients with OSA (apnea-hypopnea index ≥ 5 events/h) were then placed into symptom subtypes based on responses to survey questions using latent class analysis. Cardiovascular events (stroke, myocardial infarction, unstable angina, bypass grafting, percutaneous coronary intervention, cardiac resynchronization therapy, defibrillation) occurring within 8 years of polysomnogram were identified by linkage to provincial health databases. RESULTS: 1,607 patients were studied, of whom 1,292 had OSA. One hundred forty first events occurred within 8 years of polysomnogram. Patients in the excessively sleepy with disturbed sleep subtype had a significantly increased rate of events compared to the minimally symptomatic subtype (hazard ratio = 2.25, 95% confidence interval: 1.02-4.94; P = .04). Two symptoms (restless legs and dozing off or sleeping while talking to someone) were significantly associated with future risk of cerebrovascular disease (hazard ratio = 1.68, 1.12-2.49 and 4.23, 1.61-11.16, respectively). CONCLUSIONS: Patients with OSA in the clinic who are in the excessively sleepy with disturbed sleep subtype are significantly more likely to have a future cardiovascular event. This underscores the importance of understanding clinical heterogeneity and incorporating symptom subtype definitions into routine clinical care. CITATION: Allen AJH, Jen R, Mazzotti DR, et al. Symptom subtypes and risk of incident cardiovascular and cerebrovascular disease in a clinic-based obstructive sleep apnea cohort. J Clin Sleep Med. 2022;18(9):2093-2102.

Sex Differences in the Management of Oral Anticoagulation and Outcomes for Emergency Department Presentation of Incident Atrial Fibrillation.

STUDY OBJECTIVE: To examine sex differences in oral anticoagulation management and outcomes among patients with incident nonvalvular atrial fibrillation presenting to the emergency department (ED). METHODS: We identified patients older than 20 years presenting to the ED with incident nonvalvular atrial fibrillation between April 1, 2012, and March 30, 2019, using linked administrative databases in Alberta, Canada. We assessed the use of and adherence to oral anticoagulants at 1 year using the proportion of days covered for direct oral anticoagulants and time in therapeutic range for warfarin. Outcomes included stroke, heart failure, and all-cause mortality at 1 year. RESULTS: Of the 28,886 patients with nonvalvular atrial fibrillation presenting to ED, 44% were females. After adjustment, the rate of oral anticoagulant use was 5% lower in females with a guideline indication than that in males (adjusted hazard ratio 0.95, 95% confidence interval [CI] 0.91 to 0.99) discharged home, and there was no difference among admitted patients (adjusted hazard ratio 1.00, 95% CI 0.96 to 1.05). Females had high adherence to direct oral anticoagulants (≥80% proportion of days covered) compared to males (discharged: 77.7% versus 74.0%; admitted: 80.0% versus 76.7%; adjusted odds ratio for females: 1.15, 95% CI 1.02 to 1.29). More than half of the females and males had poor warfarin control (time in therapeutic range <65%) regardless of discharge status. In multivariable analyses, there was no sex difference in outcomes except a 1.48-fold (95% CI 1.14 to 1.92) higher risk of stroke in females. CONCLUSION: Females with incident nonvalvular atrial fibrillation discharged from the ED are less likely to receive oral anticoagulants than males. When oral anticoagulant treatment is initiated, females have high adherence to direct oral anticoagulants, and both the sexes have poor warfarin control. At 1 year, females were at a significantly higher risk of developing stroke.

Effectiveness of crizotinib versus entrectinib in ROS1-positive non-small-cell lung cancer using clinical and real-world data.

Aims: To compare clinical trial results for crizotinib and entrectinib in ROS1-positive non-small-cell lung cancer and compare clinical trial data and real-world outcomes for crizotinib. Patients & methods: We analyzed four phase I-II studies using a simulated treatment comparison (STC). A STC of clinical trial versus real-world evidence compared crizotinib clinical data to real-world outcomes. Results: Adjusted STC found nonsignificant trends favoring crizotinib over entrectinib: objective response rate, risk ratio = 1.04 (95% CI: 0.85-1.28); median duration of response, mean difference = 16.11 months (95% CI: -1.57- 33.69); median progression-free survival, mean difference = 3.99 months (95% CI: -6.27-14.25); 12-month overall survival, risk ratio = 1.01 (95% CI: 0.90-1.12). Nonsignificant differences were observed between the trial end point values and the real-world evidence for crizotinib. Conclusions: Crizotinib and entrectinib have comparable efficacy in ROS1-positive non-small-cell lung cancer.

A Systematic Literature Review of the Epidemiology, Health-Related Quality of Life Impact, and Economic Burden of Immunoglobulin A Nephropathy.

Introduction: This systematic literature review analyzed published evidence on IgA nephropathy (IgAN), focusing on US epidemiology, health-related quality of life (HRQoL), and economic burden of illness. Methods: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, Embase®, MEDLINE®, Cochrane, and Econlit (January 2010 to June 2020) were searched, along with relevant congresses (2017-2020). Results: Of 123 epidemiologic studies selected for data extraction, 24 reported IgAN diagnosis rates ranging from 6.3% to 29.7% among adult and pediatric patients undergoing renal biopsy, with all reported US rates <15%. No US studies reported IgAN prevalence. A meta-analysis of US studies calculated an annual incidence of 1.29/100 000 people, translating to an annual US incidence of 4236 adults and children. Relative to Europe, the United States had more patients diagnosed with IgAN in later chronic kidney disease stages. US rates of transition to end-stage renal disease (ESRD) ranged from 12.5% to 23% during 3-3.9 years of observation, rising to 53% during 19 years of observation. Across 8 studies reporting HRQoL, pain and fatigue were the most reported symptoms, and patients consistently ranked kidney function and mortality as the most important treatment outcomes. Patients with glomerulopathy reported worse mental health than healthy controls or hemodialysis patients; proteinuria was significantly associated with poorer HRQoL and depression. Conclusion: While economic evidence in IgAN remains sparse, management of ESRD is a major cost driver. IgAN is a rare disease where disease progression causes increasing patient burden, underscoring the need for therapies that prevent kidney function decline and HRQoL deterioration while reducing mortality.

Quality of life analyses in patients with multiple myeloma: results from the Selinexor (KPT-330) Treatment of Refractory Myeloma (STORM) phase 2b study.

BACKGROUND: Selinexor is an oral, selective nuclear export inhibitor. STORM was a phase 2b, single-arm, open-label, multicenter trial of selinexor with low dose dexamethasone in patients with penta-exposed relapsed/refractory multiple myeloma (RRMM) that met its primary endpoint, with overall response of 26% (95% confidence interval [CI], 19 to 35%). Health-related quality of life (HRQoL) was a secondary endpoint measured using the Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM). This study examines impact of selinexor treatment on HRQoL of patients treated in STORM and reports two approaches to calculate minimal clinically important differences for the FACT-MM. METHODS: FACT-MM data were collected at baseline, on day 1 of each 4-week treatment cycle, and at end of treatment (EOT). Changes from baseline were analyzed for the FACT-MM total score, FACT-trial outcome index (TOI), FACT-General (FACT-G), and the MM-specific domain using mixed-effects regression models. Two approaches for evaluating minimal clinically important differences were explored: the first defined as 10% of the instrument range, and the second based on estimated mean baseline differences between Eastern Cooperative Oncology Group performance status (ECOG PS) scores. Post-hoc difference analysis compared change in scores from baseline to EOT for treatment responders and non-responders. RESULTS: Eighty patients were included in the analysis; the mean number of prior therapies was 7.9 (standard deviation [SD] 3.1), and mean duration of myeloma was 7.6 years (SD 3.4). Each exploratory minimal clinically important difference threshold yielded consistent results whereby most patients did not experience HRQoL decline during the first six cycles of treatment (range: 53.9 to 75.7% for the first approach; range: 52.6 to 72.9% for the second). Treatment responders experienced less decline in HRQoL from baseline to EOT than non-responders, which was significant for the FACT-G, but not for other scores. CONCLUSION: The majority of patients did not experience decline in HRQoL based on minimal clinically important differences during early cycles of treatment with selinexor and dexamethasone in the STORM trial. An anchor-based approach utilizing patient-level data (ECOG PS score) to define minimal clinically important differences for the FACT-MM gave consistent results with a distribution-based approach. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov under the trial-ID NCT02336815 on January 8, 2015.

Circulating levels of cell adhesion molecules and risk of cardiovascular events in obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) patients are at increased risk of cardiovascular disease (CVD). Cell adhesion molecules (CAM) are increased in OSA and CAM are also implicated in the development of CVD. RESEARCH QUESTION: Do CAM (ICAM-1, VCAM-1 and E-selectin) have prognostic value in identifying risk of cardiovascular events in OSA? STUDY DESIGN AND METHODS: Patients with suspected OSA referred for a polysomnogram provided a fasting blood sample. Plasma levels of ICAM-1, VCAM-1 and E-selectin were determined by multiplex Luminex Assay (Milliporesigma ON, Canada). Cardiovascular events were determined by deterministic linkage to provincial health databases. RESULTS: 418 patients were included in the analysis. Mostly male (68.2%), mean age of 50.7 yrs, median AHI 16.5 events/hour, and mean BMI of 31.7 kg/m2. 36 cardiovascular events occurred in 8-yrs of follow up. Higher levels of ICAM-1 were associated with developing CVD (HR = 3.65 95% CI 1.40-9.53, 2nd and 3rd tertiles vs. 1st tertile), including in patients with OSA (HR = 3.1 95% CI 1.16-8.25). E-selectin was significantly associated with cardiovascular events in patients with moderate to severe OSA (HR = 3.31 95% CI 0.94-11.72, 2nd and 3rd tertiles vs. 1st tertile) but not in patients without moderate to severe OSA (HR = 0.67 95% CI 0.19-2.38), p-value for interaction = 0.07. INTERPRETATION: In a suspected OSA cohort, patients with higher levels of ICAM-1 (>816 ng/ml) were significantly more likely to experience a cardiovascular event within 8 years after PSG. In moderate to severe OSA patients, a higher E-selectin (>36.4 ng/ml) was significantly associated with cardiovascular events.

Comparative effectiveness of glasdegib versus venetoclax combined with low-dose cytarabine in acute myeloid leukemia.

Background: Two combination therapies recently approved and recommended for use in combination with low-dose cytarabine (LDAC) in acute myeloid leukemia patients unfit for intensive chemotherapy are glasdegib+LDAC and venetoclax+LDAC. Materials & methods: An indirect treatment comparison used median overall survival, overall survival hazard ratios, complete remission (CR), CR+CR with incomplete blood count recovery and transfusion independence to assess comparative effectiveness, and a simulated treatment comparison accounted for differences in patient characteristics between trials. Results: Differences in efficacy between glasdegib+LDAC and venetoclax+LDAC were suggestive and not statistically significant. Conclusion: With no significant differences in comparative effectiveness, considerations such as safety profiles, burden of administration and patient preference are likely to guide treatment decisions.

Health-related quality of life and utility outcomes with selinexor in relapsed/refractory diffuse large B-cell lymphoma.

Aim: Evaluate health-related quality of life (HRQoL) and health utility impact of single-agent selinexor in heavily pretreated patients with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Functional Assessment of Cancer Therapy (FACT) - Lymphoma and EuroQoL five-dimensions five-levels data collected in the single-arm Phase IIb trial SADAL (NCT02227251) were analyzed with mixed-effects models. Results: Treatment responders maintained higher FACT - Lymphoma (p ≤ 0.05), FACT - General (p < 0.05) and EuroQoL five-dimensions five-levels index scores (p < 0.001) beginning in cycle 3. The estimated difference in health state utilities for treatment response and progressive disease was both statistically significant and clinically meaningful (mean difference: 0.07; p = 0.001). Conclusion: In patients with relapsed/refractory diffuse large B-cell lymphoma, objective response to selinexor was associated with HRQoL maintenance, reduction in disease-related HRQoL decrements and higher health utilities.

Lay abstract This work examined quality of life (QoL) among patients with relapsed/refractory diffuse large B-cell lymphoma with two to five prior therapies who received single-agent selinexor in the SADAL clinical trial. Analysis of patient-reported Functional Assessment of Cancer Therapy ­ Lymphoma and EuroQoL five-dimensions five-levels data showed that patients who had objective clinical response to selinexor maintained their QoL over the course of treatment. Grade ≥3 adverse events and serious adverse events were not associated with clinically meaningful negative QoL impacts. Clinical trial registration: NCT02227251 (ClinicalTrials.gov).

Empirical Insights When Defining the Population Burden of Atrial Fibrillation and Oral Anticoagulation Utilization Using Administrative Data.

Health administrative data are routinely used to assess disease burden, quality of care, and outcomes for atrial fibrillation (AF). Governments, administrators, and researchers define cohorts differently, based on 3 key factors: the case definition algorithm to identify AF, inclusion/exclusion of transient AF, and the lookback period to identify cases. We assessed the impact of varying these key factors on estimates of the use of guideline-indicated oral anticoagulation (OAC). Hospitalization, ED, and outpatient claim databases were linked in British Columbia. AF was defined by ICD-9 or 10 codes 427.3x or I48.x. We examined a specific (1 hospital or 1 ED or 2 outpatient) vs a sensitive (1 hospital or ED or outpatient) algorithm; inclusion/exclusion of AF associated with open-heart surgery; and lookback periods of 1 to 10 years. We found the more specific AF definition increased OAC utilization by 5% (58.7% vs 53.4%); excluding AF associated with open-heart surgery increased OAC utilization by 0.7% to 2.3%; and each additional lookback year identified more prevalent cases but reduced OAC utilization by approximately 1%. In 40 scenarios, generated by varying all 3 key factors, OAC utilization ranged from 52% to 72%. Assuming a ceiling of 90%, the estimated "treatment gap" therefore varied from 18% to 38%. The 2-fold variation in the OAC treatment gap was based entirely on cohort definition. This has significant implications for health policy and quality indicators.

Sex Differences in Cardiac Medication Use Post-Catheterization in Patients Undergoing Coronary Angiography for Stable Angina with Nonobstructive Coronary Artery Disease.

BACKGROUND: Treatment of patients with stable angina and nonobstructive coronary artery disease (CAD) has not been well characterized. We comparatively evaluated medication use in males and females with stable angina with no CAD, nonobstructive CAD, and obstructive CAD. METHODS: We studied all patients ≥20 years old with stable angina undergoing coronary angiography in British Columbia (BC), Canada, from January 2008 to March 2010 (n = 7,535). No CAD, nonobstructive CAD, and obstructive CAD were defined as 0%, 1%-49%, and ≥50% luminal narrowing in any epicardial coronary artery, respectively. Medication use, 3 months before and 3 months following angiography, was obtained through BC PharmaNet for angiotensin-converting enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), beta-blockers, statins, antiplatelet agents, and prescriptions for all three ACE-I/ARBs, beta-blockers, and statins (combination therapy). RESULTS: Following angiography, patients with no and nonobstructive CAD had significantly lower rates of prescription use of all medications, including combination therapy, than patients with obstructive CAD (p < 0.001). Use of ACE-I/ARBs, beta-blockers, statins, and combination therapy did not differ by sex, but females had higher use of CCB in all CAD groups, and clopidogrel in nonobstructive and obstructive CAD groups, compared to males. CONCLUSIONS: In patients with stable angina, medication use following angiography is low in nonobstructive CAD with only 58.9% prescribed a statin and 19.4% on combination therapy at 3 months. There are no important sex differences in medication use in any CAD category post-angiography. Future studies should explore methods of improving quality of care in patients with nonobstructive CAD.

Cardiac Medication Use in Patients with Acute Myocardial Infarction and Nonobstructive Coronary Artery Disease.

IMPORTANCE: Patients with acute myocardial infarction (MI) and nonobstructive coronary artery disease (CAD) have an elevated cardiac event rate, suggesting that these patients may benefit from cardiac medication. OBJECTIVE: We evaluated the rates of cardiac medication use 3 months before angiography and 3 months following clinically indicated angiography for MI in patients with no CAD, nonobstructive CAD, and obstructive CAD. We also examined the sex differences in cardiac medication use 3 months following angiography in patients by extent of angiographic CAD. METHODS: We studied patients ≥20 years old with MI undergoing coronary angiography in British Columbia, Canada, from January 1, 2008, to March 31, 2010 (n = 3,841). No CAD, nonobstructive CAD, and obstructive CAD were defined as 0%, 1% to 49%, and ≥50% luminal narrowing in any epicardial coronary artery, respectively. Medication use, 3 months before and 3 months following angiography, was obtained through British Columbia PharmaNet for angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), beta-blockers, statins, and antiplatelet agents. Optimal medical therapy (OMT) was defined as filled prescriptions for all three: ACE-Is/ARBs, beta-blockers, and statins. RESULTS: Following angiography, in all medication categories except CCBs, patients with no CAD and nonobstructive CAD had significantly lower rates of prescriptions filled than patients with obstructive CAD (all p < 0.001). After adjusting for age and prior medication use, patients with nonobstructive CAD were still less likely to receive these medications than patients with obstructive CAD, including OMT with an odds ratio = 0.25 (95% confidence interval: 0.18-0.36). There were no significant sex differences in medication use 3 months postangiography. CONCLUSIONS: In post-MI patients, medication use following angiography is significantly lower in nonobstructive CAD than obstructive CAD at 3 months. While sex was not an independent predictor of medication use 3 months post-catheterization, future studies should explore methods of improving medication use in both females and males with nonobstructive CAD post-MI.

Obstructive sleep apnoea and frequency of occupational injury.

We sought to determine whether patients with obstructive sleep apnoea (OSA) are at increased risk of occupational injury (OI). Patients referred to the University of British Columbia Hospital Sleep Laboratory for suspected OSA (May 2003 to July 2011 were recruited and rates and types of validated OI (that caused at least 1 day of disability) in the 5 years prior to polysomnography were calculated. In a sample of 1236, patients with OSA were twice as likely (OR=1.93, 95% CI 1.06 to 3.50, p=0.03) to suffer at least one OI compared with patients without OSA. This association was attenuated (OR=1.76, CI 0.86 to 3.59, p=0.12) after controlling for confounders. In a secondary analysis, patients with OSA were almost three times more likely (OR=2.88, CI 1.02 to 8.08, p=0.05) to suffer from an injury more likely related to reduced vigilance (eg, a fall or commercial motor vehicle crash) when compared with patients without OSA, and this again was attenuated after controlling for confounders (OR=2.42, CI 0.085 to 6.93, p=0.10).