Real-world evidence comparing oral anticoagulants in non-valvular atrial fibrillation: a systematic review and network meta-analysis.

Aim: To compare real-world effectiveness/safety of non-vitamin K antagonist oral anticoagulants and vitamin K antagonists among patients with non-valvular atrial fibrillation. Materials & methods: A systematic review of electronic databases yielded 7661 citations published from January 2013 to January 2020. Fifty-five studies were included in Bayesian network meta-analyses of hazard ratios. Results & conclusion: In comparison with vitamin K antagonists, apixaban, dabigatran and rivaroxaban were associated with a reduced risk of stroke or systemic embolism, ischemic stroke, intracranial hemorrhage and all-cause mortality. Apixaban, dabigatran and edoxaban, but not rivaroxaban, were associated with a reduced risk of major bleeding. This study confirmed the effectiveness and safety of non-vitamin K antagonist oral anticoagulants for the treatment of non-valvular atrial fibrillation in real-world settings, consistent with clinical trial evidence.

This study aimed to compare real-world effectiveness/safety of non-vitamin K antagonist oral anticoagulants and vitamin K antagonists among patients with non-valvular atrial fibrillation. A systematic review was conducted from January 2013 to January 2020, and a total of 7661 references were assessed for relevance. Fifty-five studies were combined in the analysis; in comparison with vitamin K antagonists, apixaban, dabigatran and rivaroxaban were associated with a reduced risk of stroke or systemic embolism, ischemic stroke, intracranial hemorrhage and all-cause mortality. Apixaban, dabigatran and edoxaban, but not rivaroxaban, were associated with a reduced risk of major bleeding. This study confirmed the effectiveness and safety of non-vitamin K antagonist oral anticoagulants for the treatment of non-valvular atrial fibrillation in real-world settings, consistent with clinical trial evidence.

Cost-effectiveness analysis of apixaban versus vitamin K antagonists for antithrombotic therapy in patients with atrial fibrillation after acute coronary syndrome or percutaneous coronary intervention in Spain.

BACKGROUND/OBJECTIVE: AUGUSTUS trial demonstrated that, for patients with atrial fibrillation (AF) having acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI), an antithrombotic regimen with apixaban and P2Y12 resulted in less bleeding, fewer hospitalizations, and similar ischemic events than regimens including a vitamin K antagonist (VKA), aspirin, or both. This study objective was to evaluate long-term health and economic outcomes and the cost-effectiveness of apixaban over VKA, as a treatment option for patients with AF having ACS/PCI. METHODS: A lifetime Markov cohort model was developed comparing apixaban versus VKA across multiple treatment strategies (triple [with P2Y12 + aspirin] or dual [with P2Y12] therapy followed by monotherapy [apixaban or VKA]; triple followed by dual and then monotherapy; dual followed by monotherapy). The model adopted the Spanish healthcare perspective, with a 3-month cycle length and costs and health outcomes discounted at 3%. RESULTS: Treatment with apixaban resulted in total cost savings of €883 and higher life years (LYs) and quality-adjusted LYs (QALYs) per patient than VKA (net difference, LYs: 0.13; QALYs: 0.11). Bleeding and ischemic events (per 100 patients) were lower with apixaban than VKA (net difference, -13.9 and -1.8, respectively). Incremental net monetary benefit for apixaban was €3,041, using a willingness-to-pay threshold of €20,000 per QALY. In probabilistic sensitivity analysis, apixaban was dominant in the majority of simulations (92.6%), providing additional QALYs at lower costs than VKA. CONCLUSIONS: Apixaban was a dominant treatment strategy than VKA from both the Spanish payer's and societal perspectives, regardless of treatment strategy considered.

Real-world persistence to direct oral anticoagulants in patients with atrial fibrillation: a systematic review and network meta-analysis.

OBJECTIVE: To conduct a systematic review and network meta-analysis of real-world evidence comparing adherence, persistence, cost, and utilization between oral anticoagulant (OAC) in non-valvular atrial fibrillation (NVAF) patients. METHODS: A systematic search of MEDLINE and Embase (inception-July 2019) was conducted for published observational cohort studies comparing outcomes between ≥2 OACs. A network meta-analysis was performed to estimate odds ratios for non-persistence using a random-effects model. RESULTS: There were 80 studies evaluating the outcomes of interest. However, due to a paucity in adherence studies and heterogeneity in adherence, cost, and utilization definitions, persistence was the focus of this network meta-analysis. There were 36 studies evaluating non-persistence in 395,593 participants, 24 of which used 3 gap definitions (30-, 60-, and 90-days); 18 unique studies evaluating non-persistence at 12 months were included in the network meta-analysis. Using 30- and 90-day gaps, all NOACs, when compared with VKAs, had lower odds of non-persistence (30-day OR (95%CI): apixaban: 0.63 (0.58, 0.69); rivaroxaban: 0.69 (0.62, 0.76); dabigatran: 0.89 (0.82, 0.97); 90-day OR (95%CI): apixaban: 0.33 (0.22, 0.47); rivaroxaban: 0.47 (0.36, 0.61); dabigatran 0.61 (0.44, 0.85)). When using a 60-day gap, dabigatran had higher odds of non-persistence vs VKAs (OR: 1.35; 95%CI: 1.12, 1.61), but there were no significant differences for apixaban and rivaroxaban. Apixaban had the lowest probability of non-persistence across the 3-gap definitions (95.7% with 30-day gap, 76.9% with 60-day gap, 98.4% with 90-day gap). CONCLUSIONS: The current findings, despite multiple limitations, can raise awareness and understanding of real-world persistence associated with OAC therapy in NVAF patients.

Systematic review of societal costs associated with stroke, bleeding and monitoring in atrial fibrillation.

Aim: Economic consequences associated with the rise in nonvitamin K antagonist oral anticoagulant use on a societal level remain unclear. Materials & methods: Evidence from the past decade on the societal economic burden associated with stroke, bleeding and international normalized ratio monitoring in atrial fibrillation was collected and summarized through a systematic literature review. Results: There were 14 studies identified that reported indirect costs, which were highest among patients with hemorrhagic stroke and intracranial hemorrhage. The contribution of indirect costs to the total was marginal during acute treatment but substantially increased (30-50%) 2 years after stroke and bleeding events. Conclusion: Limited data were available on societal costs in atrial fibrillation and further research is warranted.

Enhanced Long-Term Brain Magnetic Resonance Imaging Evaluation of Children with Sickle Cell Disease after Hematopoietic Cell Transplantation.

Progressive neurovasculopathy in children with sickle cell disease (SCD) results in decreased cognitive function and quality of life (QoL). Hematopoietic cell transplantation (HCT) is believed to halt progression of neurovasculopathy. Quantitative analysis of T2-weighted fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) for white matter hyperintensity (WMH) burden provides a meaningful estimate of small vessel cerebrovascular disease. We asked if quantitative analysis of WMH could complement standardized clinical assessment of MRI/magnetic resonance angiography (MRA) for assessing SCD central nervous system vasculopathy before and after HCT. Retrospective longitudinal clinical examination of scheduled annual MRI/MRA and quantitative analysis of WMH were performed before and 1 to 7 years after HCT at scheduled annual intervals, along with QoL measurements, in children who had engrafted after HCT. Of 18 patients alive and persistently engrafted (median age, 9.1 years), pretransplantation MRI demonstrated that 9 and 5 had sickle-related stroke and/or small infarcts, respectively. Patients were divided into WMH severity tertiles based on pretransplantation WMH volumes. MRI and WMH were assessed 1 to 7 years after HCT. MRI/MRA and WMH volume were stable or slightly better in 17 of 18 patients. By parent- and self-report, post-HCT QoL improved for children in the lowest WMH tertile significantly more than in the other groups. Based on this single-institution retrospective sample, we report that WMH appears to quantitatively support MRI-based findings that HCT stabilizes long-term small and large vessel cerebrovascular changes and is associated with the degree of improved QoL. While confirmation in larger prospective studies and evaluation by neurocognitive testing are needed, these findings suggest that WMH is a useful biomarker of neurovasculopathy after transplantation for SCD.

Feasibility of baseline neurocognitive assessment using Cogstate during the first month of therapy for childhood leukemia.

PURPOSE: Neurocognitive impairment is frequently observed among acute lymphoblastic leukemia (ALL) survivors within the domains of intelligence, attention, processing speed, working memory, learning, and memory. However, few have investigated treatment-induced changes in neurocognitive function during the first months of treatment. Additionally, dysfunction during treatment may be preceded by changes in biomarkers measured within cerebrospinal fluid (CSF). Identification of acute declines in neurocognitive function, as well as predictive genotypes or biomarkers, could guide therapeutic trials of protective interventions. METHODS: This study collects CSF while prospectively assessing neurocognitive functioning (working memory, executive function, learning, processing speed, and attention) of ALL patients using the Cogstate computerized battery at six time points during and after the 2 years of leukemia treatment on a Dana-Farber Cancer Institute ALL Consortium trial. RESULTS: Baseline data collected during the first 3 weeks of induction chemotherapy indicate reliable data as all subjects (N = 34) completed Cogstate baseline testing, while completion and performance checks indicate that 100 % of subjects completed testing and complied with test requirements. The majority (85 %) exhibited normal function compared with age peers. Preliminary analysis of CSF biomarkers (folate, homocysteine, 8-isoprostane, and myelin basic protein) similarly reveals values at baseline within expected normal ranges. CONCLUSIONS: The first month of induction therapy for ALL is a reliable baseline for detecting treatment-induced changes in neurocognitive functioning. Consequently, serial data collection might identify subgroups of ALL patients at increased risk for neurocognitive decline, warranting proactive interventions to improve their level of functioning both during treatment and into survivorship.

Group-Based Trajectory Modeling of Distress and Well-Being Among Caregivers of Children Undergoing Hematopoetic Stem Cell Transplant.

Objective: To examine the trajectories of caregiver psychological responses in the year following their child's hematopoetic stem cell transplant (HSCT), and whether cognitive and social processing strategies differentiated between trajectories. Method: One hundred and eight caregivers randomized to the control condition of a cognitive-behavioral intervention study completed measures of distress, coping, and social support at baseline, 1 month, 6 months, and 1 year post HSCT of their child. Results: The majority reported moderate or low anxiety, depression, or distress that decreased over time, but a small group demonstrated high anxiety, depression, or distress that persisted or increased over time. Maladaptive coping was highest among caregivers in the high-persistent distress subgroup compared with the moderate-decreasing and low-stable groups. Adaptive coping was minimally associated with trajectory subgroups. Conclusions: Screening HSCT caregivers for distress and maladaptive coping may be useful in identifying caregivers likely to experience persistently high distress who may benefit from psychological intervention.

Is employment status in adults over 25 years old associated with nonmedical prescription opioid and stimulant use?

PURPOSE: Nonmedical use of prescription opioid and stimulants (NMUPO and NMUPS, respectively) has declined in recent years, but remains an important public health problem. Evidence regarding their relationships with employment status remains unclear. We determined the relationship between employment status and NMUPO and NMUPS. METHODS: We analyzed a cross-sectional, nationally representative, weighted sample of 58,486 adults, ages 26 years and older, using combined 2011-2013 data from the National Survey on Drug Use and Health (NSDUH). We fit two crude and two adjusted multivariable logistic regression models to assess the relationship between our two different outcomes of interest: (1) past-year NMUPO and (2) past-year NMUPS, and our exposure of interest: employment status, categorized as (1) full time, (2) part time, (3) unemployed, and (4) not in the workforce. Our adjusted models featured the following covariates: sex, race, age, marital status, and psychological distress, and other nonmedical use. RESULTS: Prevalence of NMUPO was higher than NMUPS (3.48 vs. 0.72%). Unemployed participants had the highest odds of NMUPO [aOR 1.45, 95% CI (1.15-1.82)], while those not in the workforce had the highest odds of NMUPS [aOR 1.71, 95% CI (1.22-2.37)]. Additionally, part-time and unemployed individuals had increased odds of NMUPS [aORs, 95% CI 1.59 (1.09-2.31) and 1.67 (1.11-2.37) respectively], while those not in the workforce had decreased odds of NMUPO [aOR 0.82, 95% CI (0.68-0.99)] relative to full-time participants. CONCLUSIONS: There is a need for adult prevention and deterrence programs that target nonmedical prescription drug use, especially among those unemployed or not in the workforce.

Interpersonal Sensitivity and Sexual Functioning in Young Men with Testicular Cancer: the Moderating Role of Coping.

BACKGROUND: Interpersonal sensitivity is characterized by the predisposition to perceive and elicit criticism, rejection, and negative social evaluation. It may be linked to poorer physical or functional health outcomes, particularly in the interpersonal context (cancer-related sexual dysfunction). PURPOSE: This study tested the association of interpersonal sensitivity with sexual functioning following testicular cancer in young men and whether this association is moderated by coping processes. METHOD: Men ages 18 to 29 (N = 171; M age = 25.2, SD = 3.32) with a history of testicular cancer were recruited via the California State Cancer Registry and completed questionnaire measures including assessments of interpersonal sensitivity, sexual functioning, and approach and avoidance coping. RESULTS: Regression analysis controlling for education, age, partner status, ethnic status, and time since diagnosis revealed that higher interpersonal sensitivity was significantly related to lower sexual functioning (ß = -0.18, p < 0.05). Cancer-related approach-oriented coping was associated with better sexual functioning (ß = 0.19, p < 0.05). No significant association was observed for avoidance coping (ß = -0.08, ns). Approach-oriented coping, but not avoidance, moderated the relationship with sexual functioning (ß = 0.19, p < 0.05), such that higher interpersonal sensitivity was more strongly associated with lower functioning among men with relatively low use of approach coping. CONCLUSION: Interpersonal sensitivity may be an important individual difference in vulnerability to sexual dysfunction after testicular cancer. Enhancement of coping skills may be a useful direction for intervention development for interpersonally sensitive young men with cancer.

Health-related quality of life after allogeneic hematopoietic stem cell transplantation for sickle cell disease.

Sickle cell disease (SCD) is a hereditary hemoglobinopathy that affects over 100,000 people in the United States. Patients with SCD are known to experience suboptimal health-related quality of life (HRQoL). In addition to the physical manifestations of SCD, psychological and social stress, along with academic difficulties, secondary to the chronicity of the disease and its complications often affect patients with SCD. Although medical therapy of SCD has improved, allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative therapy. The objective of this study was to measure HRQoL before and after allo-HCT by assessing physical, psychological, and social functioning in patients with SCD who have undergone reduced-toxicity conditioning (busulfan/fludarabine/alemtuzumab) followed by allo-HCT. Patients < 21 years of age undergoing allo-HCT (matched siblings and unrelated donors) for SCD and their primary caregiver were enrolled using either the English or Spanish version of the PedsQoL 4.0. Data were collected at 3 time points: before allo-HCT and on days 180 and 365 after allo-HCT. The change in HRQoL from baseline was assessed with unadjusted and adjusted mixed-effects models in which subjects were treated as random effects, and variance component structure was used. Seventeen patients and 23 primary caregivers were enrolled and reported a mean overall HRQoL of 66.05 (SD, 15.62) and 72.20 (SD, 15.50) at baseline, respectively. In the patient-reported analysis with adjusted mixed-effects models, the estimated improvements in overall HRQoL were 4.45 (SE, 4.98; P = .380) and 16.58 (SE, 5.06; P = .003) at 180 and 365 days, respectively, after allo-HCT. For parent-reported overall HRQoL, the estimated improvements were 1.57 (SE, 4.82; P = .747) and 9.28 (SE, 4.62; P = .053) at 180 and 365 days, respectively, after allo-HCT. Similar results were found across the physical, social, and emotional HRQoL domains with mixed-effects models after adjustment of demographic and medical variables. In addition to the alleviation of clinical manifestations of SCD, these patients demonstrated significant improvement in most aspects of HRQoL by 1 year after allo-HCT. These data represent the trajectory of HRQoL during the initial year of follow-up within this population and should be integrated into the decision-making process when considering allo-HCT in patients with SCD.