Canadian Adalimumab Post-Marketing Observational Epidemiological Study Effectiveness in Psoriatic Arthritis (COMPLETE-PsA): 12-Month Results of Comparative Effectiveness of Adalimumab and nbDMARDs

Objective COMPLETE-PsA was an observational study of biologic-naïve Canadian adults with active psoriatic arthritis (PsA) treated with adalimumab or a non-biologic disease-modifying antirheumatic drug (nbDMARDs) regimen, after inadequate response/intolerance to a current nbDMARD treatment regimen. The aim of this analysis was to assess 12-month effectiveness of adalimumab versus nbDMARDs. Methods Patients enrolled between March 2012 and November 2017 were included. The following clinical parameters and patient-reported outcomes were collected/calculated per routine care: DAPSA28, DAS28, ESR, CRP, MDGA, PtGA, pain, HAQ-DI, SF-12, enthesitis, dactylitis, BSA, and time to achieving ACR50, ACR70 and modified MDA (mMDA). Results Two hundred seventy-seven adalimumab-treated and 148 nbDMARD-treated patients were included. At baseline, adalimumab-treated patients were less likely to be employed; had longer morning stiffness; higher DAPSA28, DAS28, MDGA, PtGA, pain, and HAQ-DI; and lower prevalence of dactylitis (all p<0.05). Adalimumab-treated patients showed lower baseline-adjusted DAPSA28 (16.5 vs. 26.6), DAS28 (2.8 vs. 3.9), MDGA (25.3 vs. 37.1), and ESR (10.2 vs. 15.4 mm/hr) after 3 months compared to nbDMARD-treated patients, with observed improvements maintained to month 12. Time to achievement of ACR50, ACR70, and mMDA was significantly (p<0.01) shorter among adalimumab-treated patients, with the likelihood of having dactylitis [OR: 0.4 (0.2–0.6)] and BSA<3% [2.7 (1.5–5.0)] significantly lower and higher, respectively. Switching to another biologic was less likely in adalimumab-treated vs. nbDMARD -treated patients (HR [95% CI]: 0.3 [0.2-0.5]). Conclusion In a real-world Canadian PsA population, adalimumab was more effective than nbDMARDs at reducing disease activity and the severity of skin involvement and demonstrated higher retention.

Evaluation of Continuous Inhaled Epoprostenol in the Treatment of Acute Respiratory Distress Syndrome, Including Patients With SARS-CoV-2 Infection

Background Acute respiratory distress syndrome (ARDS) management is primarily supportive. Pulmonary vasodilators, such as inhaled epoprostenol (iEPO), have been shown to improve PaO2:FiO2 (PF) and are used as adjunctive therapy. Objective To identify the positive response rate and variables associated with response to iEPO in adults with ARDS. A positive response to iEPO was defined as a 10% improvement in PF within 6 hours. Methods This retrospective study included adults with ARDS treated with iEPO. The primary endpoint was the variables associated with a positive response to iEPO. Secondary endpoints were positive response rate and the change in PF and SpO2:FiO2 within 6 hours. Statistical analysis included multivariable regression. Results Three hundred thirty-one patients were included. As baseline PF increased, the odds of responding to iEPO decreased (odds ratio [OR], 0.752, 95% CI, 0.69-0.819, p < 0.001). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related ARDS (OR 0.478, 95% CI, 0.281-0.814, p = 0.007) was associated with decreased odds of a positive response to iEPO. The total population had a 68.3% positive response rate to iEPO. SARS-CoV-2-related ARDS and non-SARS-CoV-2-related ARDS had a 59.5% and 72.7% positive response rate, respectively. iEPO significantly improved PF (71 vs 95, P < 0.001) in the whole population. Conclusion and Relevance iEPO was associated with a positive effect in a majority of moderate-to-severe ARDS patients, including patients with SARS-CoV-2-related ARDS. Lower baseline PF and non-SARS-CoV-2-related ARDS were significantly associated with a positive response to iEPO. The ability to predict which patients will respond to iEPO can facilitate better utilization.

Latitudinal but not elevational variation in blood glucose level is linked to life history across passerine birds

Macrophysiological research is vital to our understanding of mechanisms underpinning global life history variation and adaptation under diverse environments. Birds represent an important model taxon in this regard, yet our knowledge is limited to only a few physiological traits, mostly studied in temperate and Neotropical species. Here, we examined latitudinal and elevational variation in an emerging biomarker of physiological pace of life, blood glucose concentration, collected from 61 European temperate and 99 Afrotropical passerine species. Our data suggest that the slow physiological pace-of-life syndrome, indicated by lower baseline glucose level and stronger stress response, evolves convergently in lowland tropical birds across continents and is shaped by their low fecundity. In contrast, elevational variation in blood glucose levels implied a unique montane pace-of-life syndrome combining slow-paced life histories with fast-paced physiology. The observed patterns suggest an unequal importance of life history in shaping physiological adaptations associated with latitude and elevation.

Patient Compliance in Assessing Electronic Patient-Reported Outcome Measures after Urologic Surgery

<b><i>Introduction:</i></b> This study aimed to assess patient compliance with a newly established electronic patient-reported outcome measure (ePROM) system after urologic surgery and to identify influencing factors. <b><i>Methods:</i></b> Digital surveys were provided to patients undergoing cystectomy, radical or partial nephrectomy, or transurethral resection of bladder tumor via a newly established ePROM system. Participants received a baseline survey preoperatively and several follow-up surveys postoperatively. Multivariable regression analysis was performed to identify factors predicting compliance. <b><i>Results:</i></b> Of <i>N</i> = 435 eligible patients, <i>n</i> = 338 completed the baseline survey (78.0%). Patients who did not participate were significantly more likely male (<i>p</i> = 0.004) and older than 70 years (<i>p</i> = 0.005). Overall, 206/337 patients (61.3%) completed the survey at 1-month, 167/312 (53.5%) at 3-month, and 142/276 (51.4%) at 6-month follow-up. Lower baseline quality of life (odds ratio: 2.27; <i>p</i> = 0.004) was a significant predictor for dropout at 1-month follow-up. Low educational level was significantly associated with low compliance at 3- (OR: 1.92; <i>p</i> = 0.01) and 6-month follow-up (OR: 2.88; <i>p</i> &#x3c; 0.001). <b><i>Conclusion:</i></b> Acceptable compliance rates can be achieved with ePROMs following urologic surgery. Several factors influence compliance and should be considered when setting-up ePROM surveys.

Factors Associated With the Presence of Foveal Bulge in Eyes With Resolved Diabetic Macular Edema

Purpose: To evaluate factors associated with the presence of foveal bulge (FB) in resolved diabetic macular edema (DME) eyes.Methods: A total of 165 eyes with complete integrity of ellipsoid zone (EZ) at the fovea and resolved DME were divided into two groups according to the presence of FB at 6 months after intravitreal injection of ranibizumab treatment. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), outer nuclear layer (ONL) thickness, height of serous retinal detachment (SRD) and non-SRD, and inner segment (IS) and outer segment (OS) lengths of the two groups were measured and compared at baseline and each follow-up. The correlations between the presence of FB and pre- and post-treatment factors were determined by logistic regression analysis.Results: At baseline, BCVA was significantly better, and CFT and incidence and height of SRD were significantly lower in the FB (+) group (all P &lt; 0.05). At 6 months, FB was present in 65 (39.39%) eyes. Post-treatment BCVA was significantly better and OS length was significantly longer in the FB (+) group at 6 months (all P &lt; 0.05). Multivariate analysis identified younger age, better BCVA, and lower CFT before treatment as significant predictors of the existence of FB at 6 months (all P &lt; 0.05). At 6 months, better BCVA and longer OS length were significantly correlated with the existence of FB (all P &lt; 0.05).Conclusions: Factors associated with the presence of FB after the resolution of DME include younger age, better baseline BCVA and lower baseline CFT, and better post-treatment BCVA and longer post-treatment OS length.

Temporal pole blurring in temporal lobe epilepsy revealed by 3D Edge-Enhancing Gradient Echo MRI

While abnormalities of the hippocampus have been well characterized in temporal lobe epilepsy, various additional temporal lobe abnormalities have also been described. One poorly understood entity, the so-called temporal pole blurring (TPB), is one of the more frequently described neocortical abnormalities in TLE and is thought to represent dysmyelination and axonal loss due to chronic electrical perturbations in early age-onset temporal lobe epilepsy. In this study, we describe the first reported cases of TPB diagnosed by a recently described MRI sequence known as 3D Edge-Enhancing Gradient Echo (3D-EDGE), which has an effective “myelin weighting” making it exquisitely sensitive to this temporal pole dysmyelination. The value of detection of TPB lies in lateralizing seizure onset, as well as predicting a lower baseline neuropsychological performance compared to temporal lobe epilepsy without TPB. Additionally, it is critical to not mistake TPB for alternative diagnoses, such as focal cortical dysplasia or neoplasm.

Influence of Heart Rate on Left and Right Ventricular Longitudinal Strain in Patients with Chronic Heart Failure

Over the past years, a number of studies have demonstrated the relevance of strain assessed by two-dimensional speckle tracking echocardiography (STE) in evaluating ventricular function. The aim of this study was to analyze changes in left (LV) and right ventricular (RV) longitudinal strain associated with variations of heart rate (HR) in participants with and without chronic heart failure (CHF). We enrolled 45 patients, 38 of these diagnosed with CHF and carrying an implantable cardioverter defibrillator, and seven patients with pacemakers and without CHF. The frequency of atrial stimulation was increased to 90 beats/min and an echocardiogram was performed at each increase of 10 beats/min. Global LV and RV longitudinal strain (LVGLS and RVGLS, respectively) and RV free wall longitudinal strain (RVfwLS) were calculated at each HR. When analyzed as continuous variables, significant reductions in LVGLS were detected at higher HRs, whereas improvements in both RVGLS and RVfwLS were observed. Patients with a worsening of LVGLS (76% overall) were more likely to present lower baseline LV function. Only a few patients (18% for RVGLS and 16% for RVfwLS) exhibited HR-related deteriorations of RV strain measures, which was associated with lower levels of baseline RV function and higher pulmonary systolic pressures. Finally, 21 (47%) and 25 (56%) participants responded with improvements in RVGLS and RVfwLS, respectively. Our findings revealed heterogeneous RV and LV responses to increases in HR. These findings might ultimately be used to optimize cardiac functionality in patients diagnosed with CHF.

Prognostic Value and Risk Factors of Treatment-Related Lymphopenia in Malignant Glioma Patients Treated With Chemoradiotherapy: A Systematic Review and Meta-Analysis

Background: Immunotherapy has shown promising therapeutic efficacy in various cancers but not gliomas. Circulating lymphocytes play critical roles in cancer control and responses to immune checkpoint inhibitors. Treatment-related lymphopenia has been associated with poor survival in patients with various tumors. This meta-analysis evaluated the risk and impact of lymphopenia in patients with glioma.Methods: The PubMed, Embase, Web of Science, and Cochrane Library databases were comprehensively searched. Eligible studies were included if they reported the incidence and risk factors of lymphopenia and the impact of lymphopenia on survival. Stata 16.0 was used for this meta-analysis.Results: A total of 21 studies were included in the final systematic review and 20 were included in the quantitative analysis. The overall incidence of grade III/IV lymphopenia was 31.6% [95% confidence interval (CI), 22.3–40.8%]. Pooled results based on pathology of glioma revealed that the incidence in astrocytoma and astrocytoma oligodendroglioma patients was 20.2% (95% CI:5.9–34.4%), and the incidence in glioblastoma patients was 27.6% (95% CI:16.2–38.9%). Lymphopenia was associated with poor overall survival (hazard ratio, 1.99; 95% CI, 1.74–2.27; P&lt; 0.001) compared to no lymphopenia. Brain receiving radiation dose of 20 or 25 Gy, female sex, older age, lower baseline lymphocyte count, and dexamethasone dose &gt; 2 mg instead of baseline use were risk factors for lymphopenia.Conclusions: Treatment-related lymphopenia was associated with decreased survival in patients with glioma. Optimization of chemoradiation regimens, particularly in patients with concurrent risk factors, can reduce lymphopenia and potentially improve survival in the era of immunotherapy.

Differing determinants of disability trends among men and women aged 50 years and older

Background Researchers have emphasized the importance of examining how different factors affect men’s and women’s functional status over time. To date, the literature is unclear about whether sex affects the rate of change in disability in middle to older age. Researchers have further emphasized the importance of examining how different factors affect men’s and women’s functional status over time. We examined (a) sex differences in disability trends and (b) the determinants of the rate of change in disability for men and women 50 years and older. Methods This study utilized the Taiwan Longitudinal Study on Aging Survey, a nationally representative database (four waves of survey data 1996–2007, N = 3429). We modeled and compared the differences in disability trends and the influences of determinants on trends among men and women using multiple-indicator and multiple-group latent growth curves modeling (LGCM). Equality constraints were imposed on 10 determinants across groups. Results Once disability began, women progressed toward greater disability 18% faster than men. Greater age added about 1.2 times the burden to the rate of change in disability for women than men (p < 0.001). More comorbidities also added significantly more burden to baseline disability and rate of change in disability among women than men (p < 0.001), but women benefited more from higher education levels in lower baseline disability and slower rate of change. Having a better social network was associated with lower baseline disability among women only (p < 0.05). For both men and women, physically active leisure-time activities were beneficial in lower baseline disability (pmen and women < 0.001) and rate of change in disability (pmen < 0.01; pwomen < 0.05), with no significant differences between groups. Conclusions Age may widen the sex gap in the rate of change in disability. However, both sexes benefit from participating in leisure-time activities. Promoting health literacy improves health outcomes and physical function among women.

Racial Disparities in Neutrophil Counts Among Patients with Metastatic Breast Cancer during Treatment with CDK4/6 Inhibitors

Purpose: The three CDK4/6 inhibitors (CDK4/6i) approved for use in HR-positive/HER2-negative metastatic breast cancer (MBC), palbociclib, ribociclib, and abemaciclib, are generally well tolerated but their most common toxicity is neutropenia. Within the general population, neutropenia has been shown to be more common in individuals of African descent. The landmark CDK4/6i trials in MBC lacked racial diversity in their patient populations. We aimed to assess the toxicity profiles of CDK4/6i in a racially diverse population.Methods: We conducted a retrospective study at Montefiore Medical Center in patients with HR-positive/HER2-negative MBC prescribed CDK4/6i as first or subsequent lines of therapy between January 2015 and April 2020. Baseline characteristics and laboratory data at various treatment timepoints were collected. Results: A total of 182 patients were included in the final analysis. Baseline absolute neutrophil count (ANC) was lower in the Black vs. Non-Black cohort (p=0.001) but the change in ANC from baseline (Delta-ANC) was smaller in the Black vs. Non-Black cohort and the ANC at different treatment timepoints was similar between groups. There was no difference in the rate of infection or number of dose delays or reductions between Black and Non-Black cohorts. Conclusion: We analyzed toxicity profiles of 182 patients with HR-positive/HER2-negative MBC treated with CDK4/6i. Our population included 46% Black patients, who were found to have a lower baseline ANC but no increase in complications. Despite the lower baseline ANC seen in our Black cohort prior to starting CDK4/6i, treatment toxicities were similar between racial groups.