Disparities in Referral and Utilization of Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac Death.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) reduce mortality in patients with reduced left ventricular ejection fraction (LVEF). We investigated sex disparities in a contemporary Canadian population for utilization of primary prevention ICDs. METHODS: This was a retrospective cohort study on patients with reduced LVEF admitted to hospitals from 2010 to 2020 in Nova Scotia (population = 971,935). RESULTS: There were 4406 patients eligible for ICDs: 3108 (71%) men and 1298 (29%) women. The mean follow-up time was 3.9 ± 3.0 years. Rates of coronary disease were similar between men and women (45.8% vs 44.0%; P = 0.28), but men had lower LVEF (26.6 ± 5.9% vs 27.2 ± 5.8%; P = 0.0017). The referral rate for ICD was 11% (n = 487), with 13% of men (n = 403) and 6.5% of women (n = 84) referred (P < 0.001). The ICD implantation rate in the population was 8% (n = 358), with 9.5% of men (n = 296) and 4.8% of women (n = 62) (P < 0.001) receiving the device. Men were more likely than women to receive an ICD (odds ratio 2.08, 95% confidence interval 1.61-2.70; P < 0.0001)). There was no significant difference in mortality between men and women (P = 0.2764). There was no significant difference in device therapies between men and women (43.8% vs 31.1%; P = 0.0685). CONCLUSIONS: A significant disparity exists in the utilization of primary prevention ICDs between men and women in a contemporary Canadian population.

Prevalence and management of electrical lead abnormalities in cardiac implantable electronic device leads.

Background: Electrical lead abnormalities (ELAs) can result in device malfunction, leading to significant morbidity in patients with cardiac implantable electronic devices (CIEDs). Objective: We sought to determine the prevalence and management of ELAs in patients with CIEDs. Methods: This was a retrospective cohort study of patients implanted with a CIED between 2012 and 2019 at a tertiary care center. The primary outcome was ELA defined as increased capture threshold (≥2× implantation value), decreased sensing (≤0.5 implantation value), change in impedance (>50% over 3 months), or nonphysiologic potentials. A secondary outcome of device clinic utilization was also collected. Results: There were 2996 unique patients (35% female) included with 4600 leads (57% Abbott, 43% Medtronic). ELAs were observed in 135 (3%) leads, including 124 (92%) Abbott and 10 (7%) Medtronic leads (hazard ratio 9.25, P < .001). Mean follow-up was 4.5 ± 2.2 years. ELAs were associated smaller lead French size, atrial location, and Abbott leads. Lead revision was required in 28% of cases. Patients with lead abnormalities had 38% more in-clinic visits per patient year of follow-up compared with those without (P < .001). Conclusion: ELAs were more frequent in certain models, which increased rates of revision and follow-up. Identification of factors that mitigate these abnormalities to improve lead performance are required to improve care for these devices and provide efficient healthcare.

Resting state functional connectivity in SLE patients and association with cognitive impairment and blood-brain barrier permeability.

OBJECTIVE: Extensive blood-brain barrier (BBB) leakage has been linked to cognitive impairment in SLE. This study aimed to examine the associations of brain functional connectivity (FC) with cognitive impairment and BBB dysfunction among patients with SLE. METHODS: Cognitive function was assessed by neuropsychological testing (n = 77). Resting-state FC (rsFC) between brain regions, measured by functional MRI (n = 78), assessed coordinated neural activation in 131 regions across five canonical brain networks. BBB permeability was measured by dynamic contrast-enhanced MRI (n = 61). Differences in rsFC were compared between SLE patients with cognitive impairment (SLE-CI) and those with normal cognition (SLE-NC), between SLE patients with and without extensive BBB leakage, and with healthy controls. RESULTS: A whole-brain rsFC comparison found significant differences in intra-network and inter-network FC in SLE-CI vs SLE-NC patients. The affected connections showed a reduced negative rsFC in SLE-CI compared with SLE-NC and healthy controls. Similarly, a reduced number of brain-wide connections was found in SLE-CI patients compared with SLE-NC (P = 0.030) and healthy controls (P = 0.006). Specific brain regions had a lower total number of brain-wide connections in association with extensive BBB leakage (P = 0.011). Causal mediation analysis revealed that 64% of the association between BBB leakage and cognitive impairment in SLE patients was mediated by alterations in FC. CONCLUSION: SLE patients with cognitive impairment had abnormalities in brain rsFC which accounted for most of the association between extensive BBB leakage and cognitive impairment.

Mortality After Total Anterior Circulation Stroke: A 25-Year Observational Study.

BACKGROUND: Mortality remains a substantial problem after acute ischemic stroke, despite advances in acute stroke treatment over the past three decades. Mortality is particularly high among patients with Total Anterior Circulation Stroke (TACS), generally representing patients with middle cerebral artery occlusions. Notably however, these patients also stand to benefit most from new therapies including endovascular thrombectomy (EVT). In this study, we aimed to examine temporal trends in, and factors associated with, 30-day in-hospital mortality after TACS. METHODS: Information on all patients with community-onset TACS from 1994 through 2019 was extracted from a prospective acute stroke registry. Multivariate analysis was performed on the primary outcome of 30-day in-hospital mortality, as well as secondary functional outcomes. RESULTS: We studied 1106 patients hospitalized for community-onset TACS, 456 (41%) of whom experienced 30-day in-hospital mortality. Over the 25 years of observation, 30-day in-hospital mortality rose and then fell. Increased odds of mortality was associated with age and stroke severity. Decreased odds of mortality was associated with alteplase therapy and EVT, as well as presentation to hospital more than 12 hours after stroke onset. Treatment with alteplase, EVT, or both was associated with higher odds of functional independence and discharge home, and shorter lengths of stay in acute care. CONCLUSIONS: Patients receiving alteplase, EVT, or both had lower 30-day in-hospital mortality and better functional outcomes than those who were untreated. These observational data demonstrate the benefits of recanalization therapy in routine clinical practice.

Outcomes of Infants and Young Children With Relapsed Medulloblastoma After Initial Craniospinal Irradiation-Sparing Approaches: An International Cohort Study.

PURPOSE: Infant and young childhood medulloblastoma (iMB) is usually treated without craniospinal irradiation (CSI) to avoid neurocognitive late effects. Unfortunately, many children relapse. The purpose of this study was to assess salvage strategies and prognostic features of patients with iMB who relapse after CSI-sparing therapy. METHODS: We assembled a large international cohort of 380 patients with relapsed iMB, age younger than 6 years, and initially treated without CSI. Univariable and multivariable Cox models of postrelapse survival (PRS) were conducted for those treated with curative intent using propensity score analyses to account for confounding factors. RESULTS: The 3-year PRS, for 294 patients treated with curative intent, was 52.4% (95% CI, 46.4 to 58.3) with a median time to relapse from diagnosis of 11 months. Molecular subgrouping was available for 150 patients treated with curative intent, and 3-year PRS for sonic hedgehog (SHH), group 4, and group 3 were 60%, 84%, and 18% (P = .0187), respectively. In multivariable analysis, localized relapse (P = .0073), SHH molecular subgroup (P = .0103), CSI use after relapse (P = .0161), and age ≥ 36 months at initial diagnosis (P = .0494) were associated with improved survival. Most patients (73%) received salvage CSI, and although salvage chemotherapy was not significant in multivariable analysis, its use might be beneficial for a subset of children receiving salvage CSI < 35 Gy (P = .007). CONCLUSION: A substantial proportion of patients with relapsed iMB are salvaged after initial CSI-sparing approaches. Patients with SHH subgroup, localized relapse, older age at initial diagnosis, and those receiving salvage CSI show improved PRS. Future prospective studies should investigate optimal CSI doses and the role of salvage chemotherapy in this population.

Screening Criteria Evaluation for Expansion in Pulmonary Neoplasias (SCREEN).

The SCREEN study investigated screening eligibility and survival outcomes between heavy smokers and light-or-never-smokers with lung cancer to determine whether expanded risk factor analysis is needed to refine screening criteria. SCREEN is a retrospective study of 917 lung cancer patients diagnosed between 2005 and 2018 in Nova Scotia, Canada. Screening eligibility was determined using the National Lung Screening Trial (NSLT) criteria. Mortality risk between heavy smokers and light-or-never-smokers was compared using proportional-hazards models. The median follow-up was 2.9 years. The cohort was comprised of 179 (46.1%) female heavy smokers and 306 (57.8%) female light-or-never-smokers. Light-or-never-smokers were more likely to have a diagnosis of adenocarcinoma [n=378 (71.6%)] compared to heavy smokers [n=234 (60.5%); P< 0.001]. Heavy smokers were more frequently diagnosed with squamous cell carcinoma [n=111 (28.7%)] compared to light-or-never-smokers, [n=100 (18.9%); P< 0.001]. Overall, 36.9% (338) of patients met NLST screening criteria. There was no difference in 5-year survival between light-or-never-smokers and heavy smokers [55.2% (338) vs 58.5% (529); P = 0.408; HR 1.06, 95% CI 0.80-1.40; P = 0.704]. Multivariate analysis showed that males had an increased mortality risk [HR 2.00 (95% CI 1.57-2.54); P< 0.001]. Half of lung cancer patients were missed with the conventional screening criteria. There were more curable, stage 1 tumors among light-or-never-smokers. Smoking status and age alone may be insufficient predictors of lung cancer risk and prognosis. Expanded risk factor analysis is needed to refine lung cancer screening criteria.

Systematic review of diffuse hemispheric glioma, H3 G34-mutant: Outcomes and associated clinical factors.

Background: A comprehensive review and description of the clinical features that impact prognosis for patients with diffuse hemispheric glioma, H3 G34-mutant (G34-DHG) is needed. Understanding survival and prognostic features is paramount for clinical advancements and patient care. Methods: PubMed, Embase, and Google Scholar were searched for English articles published between January 1, 2012 and June 30, 2021. Eligible studies included patient(s) of any age diagnosed with an H3 G34-mutant brain tumor with at least one measure of survival or progression. Patient-level data were pooled for analyses. This study was prospectively registered in PROSPERO (CRD42021267764) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Results: Twenty-seven studies met the criteria with a total of 135 patients included. Median age at diagnosis was 15.8 years (interquartile range [IQR]: 13.3-22.0) with 90% having localized disease. Co-occurring alterations included ATRX mutation in 93%, TP53 mutation in 88%, and MGMT promoter methylation in 70%. Median time-to-progression was 10.0 months (IQR: 6.0-18.0) and median overall survival was 17.3 months (95% CI: 15.0 to 22.9). The median time from progression to death was 5.0 months (IQR: 3.0-11.7). Factors associated with survival duration were age, as patients ≥18 y/o demonstrated longer survival (hazard ratio [HR] =2.05, 95% CI: 1.16 to 3.62), and degree of upfront resection, as near or gross-total resection demonstrated longer survival compared to those with less than near-total resection (HR = 3.75, 95% CI: 2.11 to 6.62). Conclusion: This systematic review highlights available clinical data for G34-DHG demonstrating poor outcomes and important prognostic features, while serving as a baseline for future research and clinical trials.

Role of autoantibodies and blood-brain barrier leakage in cognitive impairment in systemic lupus erythematosus.

OBJECTIVE: Cognitive impairment is common in patients with SLE but the cause is unknown. The current cross-sectional study examined the association between select SLE-related autoantibodies, other serological biomarkers and extensive blood-brain barrier (BBB) leakage in patients with SLE with and without cognitive impairment. In addition, we determined whether the relationship between SLE autoantibodies, other biomarkers and cognitive impairment differed depending on the presence or absence of concurrent extensive BBB leakage. METHODS: Consecutive patients with SLE, recruited from a single academic medical centre, underwent formal neuropsychological testing for assessment of cognitive function. On the same day, BBB permeability was determined using dynamic contrast-enhanced MRI scanning. SLE autoantibodies and other serological biomarkers were measured. Regression modelling was used to determine the association between cognitive impairment, extensive BBB leakage and autoantibodies/biomarkers. RESULTS: There were 102 patients with SLE; 90% were female and 88% were Caucasian, with a mean±SD age of 48.9±13.8 years. The mean±SD SLE disease duration was 14.8±11.0 years. Impairment in one or more cognitive tests was present in 47 of 101 (47%) patients and included deficits in information processing speed (9%), attention span (21%), new learning (8%), delayed recall (15%) and executive abilities (21%). Extensive BBB leakage was present in 20 of 79 (25%) patients and was associated with cognitive impairment (15 of 20 (75%) vs 24 of 59 (41%); p=0.01) and shorter disease duration (median (IQR): 7 (8-24 years) vs 15 (2-16 years); p=0.02). No serological parameters were associated with extensive BBB leakage and there was no statistically significant association between cognitive impairment and circulating autoantibodies even after adjusting for BBB leakage. CONCLUSIONS: Extensive BBB leakage alone was associated with cognitive impairment. These findings suggest that BBB leakage is an important contributor to cognitive impairment, regardless of circulating SLE-related autoantibodies.

Home versus In-Center Dialysis and Day of the Week Hospitalization: A Cohort Study.

Background: The dialysis treatment day after the 2-day interdialytic interval (Monday/Tuesday) is associated with a heightened risk of hospitalization for patients on in-center hemodialysis (ICHD). In this national cohort study, we sought to characterize hospitalizations by day of the week for patients receiving ICHD, home HD (HHD), and peritoneal dialysis (PD) and to identify whether there were differences in the probability of a Monday/Tuesday admission for each modality type. Methods: Patients on maintenance dialysis in Canada were analyzed from 2005 to 2014 using the Canadian Organ Replacement Register. Patients on hemodialysis were categorized as those receiving ICHD, HHD, frequent ICHD, or frequent HHD (the latter two included short daily and nocturnal HD). Hospitalizations were attributed to the previous treatment if they occurred within 30 days of a treatment change. Differences in the proportion of patients experiencing a Monday/Tuesday admission with all other days of the week were compared using a generalized linear model with binomial distribution and reported using adjusted odds ratios (OR) with 95% CIs. Results: Overall, 27,430 individuals experienced 111,748 hospitalization episodes. Rates per 1000 patient days were 3.76, 2.98, 2.71, 2.16, and 2.13 for each of frequent ICHD, ICHD, PD, HHD, and frequent HHD, respectively. Compared with those on ICHD, only patients receiving frequent HHD (OR, 0.89; 95% CI, 0.81 to 0.97) and PD (OR, 0.95; 95% CI, 0.93 to 0.97) had a lower odds of experiencing a Monday/Tuesday admission. The OR was lower when restricted to hospitalization episodes for cardiovascular reasons comparing frequent HHD with ICHD (OR, 0.68; 95% CI, 0.48 to 0.96). Conclusion: In this nationally representative cohort, we identified that the probability of a Monday/Tuesday admission was lower for frequent HHD and PD compared with ICHD, most notably for hospitalizations due to cardiovascular causes. Gaining a better understanding of the reasons behind this observation may help to develop future strategies to reduce overall and cause-specific hospitalization for patients receiving dialysis.

The Impact of Transitions, a Mental Health Literacy Intervention With Embedded Life Skills for Postsecondary Students: Preliminary Findings From a Naturalistic Cohort Study.

OBJECTIVE: Mental illness is a common medical condition to onset during adolescence. Young people who leave for postsecondary life are at an especially challenging period of lifetime when many will leave home and familiar environments for prolonged periods of time. These new circumstances may put young people at risk of developing mental health problems or disorders or exacerbate existing mental disorders. Alternatively, some young people may misinterpret the normal negative emotional states occurring as a result of these new challenges as a mental disorder requiring professional intervention. We conducted a quasiexperimental cohort study to investigate the effectiveness of a mental health literacy intervention Transitions with blended life skills to address these challenges for first-year postsecondary students. METHODS: Students (n = 2,397) from five Canadian postsecondary institutions were assigned to the intervention or the control group and were administered a survey at baseline, postintervention, and at 2-month follow-up (September 2017 to February 2018). We applied generalized linear mixed effects (PROC Mixed procedure) to test the between-group difference in the post-pre/follow-up-pre and to determine the predicted least-square mean values. RESULTS: The findings showed that students who were exposed to the Transitions intervention significantly improved their mental health knowledge, decreased stigma against mental illness, improved help-seeking attitudes and behaviours, and decreased perceived stress when compared to students who had not been exposed to the intervention. However, we did not identify significant changes in general health. This may be due to the relatively short follow-up time (2 months) to determine participants' general health status. CONCLUSIONS: Transitions delivered to first-year postsecondary students may be a beneficial intervention to help young people adjust to their new postsecondary life and improve their mental health.

Frailty Severity and Hospitalization After Dialysis Initiation.

BACKGROUND: Frailty is associated with hospitalization and mortality among dialysis patients. To now, few studies have considered the degree of frailty as a predictor of hospitalization. OBJECTIVE: We evaluated whether frailty severity was associated with hospitalization after dialysis initiation. DESIGN: Retrolective cohort study. SETTING: Nova Scotia, Canada. PATIENTS: Consecutive adult, chronic dialysis patients who initiated dialysis from January 1, 2009 to June 30, 2014, (last follow-up June, 2015). METHODS: Frailty Severity, as determined by the 7-point Clinical Frailty Scale (CFS, ranging from 1 = very fit to 7 = severely frail), was measured at dialysis initiation and treated as continuous and in categories (CFS scores of 1-3, 4/5, and 6/7). Hospitalization was characterized by cumulative time admitted to hospital (proportion of days admitted/time at risk) and by the joint risk of hospitalization and death. Time at risk included time in hospital after dialysis initiation and patients were followed until transplantation or death. RESULTS: Of 647 patients (mean age: 62 ± 15), 564 (87%) had CFS scores. The mean CFS score was 4 ("corresponding to "vulnerable") ± 2 ("well" to "moderately frail"). In an adjusted negative binomial regression model, moderate-severely frail patients (CFS 6/7) had a >2-fold increased risk of cumulative time admitted to hospital compared to the lowest CFS category (IRR = 2.18, 95% confidence interval [CI] = 1.31-3.63). In the joint model, moderate-severely frail patients had a 61% increase in the relative hazard for hospitalization (hazard ratio [HR] = 1.61, 95% CI = 1.29-2.02) and a 93% increase in the relative hazard for death compared to the lowest CFS category (HR = 1.93, 95% CI = 1.16-3.22). LIMITATIONS: Potential unknown confounders may have affected the association between frailty severity and hospitalization given observational study design. The CFS is subjective and different clinicians may grade frailty severity differently or misclassify patients on the basis of limited availability. CONCLUSIONS: Among incident dialysis patients, a higher frailty severity as defined by the CFS is associated with both an increased risk of cumulative time admitted to hospital and joint risk of hospitalization and death.

CONTEXTE: La fragilité est associée à davantage d'hospitalisations et de mortalité chez les patients qui suivent des traitements de dialyze. À l'heure actuelle, peu d'études se sont penchées sur le degré de fragilité comme facteur prédictif d'hospitalization. OBJECTIFS: Nous avons évalué l'existence d'un lien entre la gravité de la fragilité et le risque d'hospitalization après l'amorce d'un traitement de dialyze. TYPE D'ÉTUDE: Étude de cohorte rétrospective. CADRE: Nouvelle-Écosse, Canada. SUJETS: L'étude porte sur des patients adultes consécutifs sous dialyze chronique et ayant entrepris leur traitement entre le 1er janvier 2009 et le 30 juin 2014 (dernier suivi en juin 2015). MÉTHODOLOGIE: L'échelle CFS (Clinical Frailty Scale) en 7 points (1 = très bonne forme physique; 7= gravement fragile) a été employée pour déterminer le niveau de gravité de la fragilité. Cette dernière a été évaluée à l'amorce de la dialyze et traitée en tant que mesure continue et selon trois niveaux d'atteinte (scores CFS de 1-3, de 4-5 et de 6-7). L'hospitalization a été caractérisée par la durée cumulative des hospitalisations (proportion de jours d'hospitalization/l'intervalle de risque) et par un risque conjoint d'hospitalization et de décès. L'intervalle de risque comprend le temps passé à l'hôpital depuis le début du traitement. Les patients ont été suivis jusqu'à la transplantation ou jusqu'au décès. RÉSULTATS: Parmi les 647 patients admissibles (âge moyen: 62 ans ± 15), 564 patients (87 %) disposaient d'un score CFS. Le score CFS moyen était de 4 (correspondant à « apparence de vulnérabilité ¼) ± 2 (« bonne forme physique ¼ à « modérément fragile ¼). Dans un modèle corrigé de régression binomiale négative, les patients jugés modérément à gravement fragiles (CFS 6/7) présentaient un risque cumulatif plus de 2 fois plus élevé d'être hospitalisés comparativement aux patients du groupe avec le score CFS le plus faible (RTI: 2,18; IC 95 %: 1,31 à 3,63). Dans le modèle conjoint, les patients jugés modérément à gravement fragiles ont présenté une augmentation de 61 % du risque relatif d'hospitalization (RR:1,61; IC 95 %: 1,29 à 2,02) et une augmentation de 93 % du risque relatif de décès comparativement aux patients avec le score CFS le plus faible (RR: 1,93; IC 95 %: 1,16 à 3,22). LIMITES: La méthodologie de l'étude (observationnelle) laisse supposer que de possibles facteurs confusionnels inconnus pourraient avoir eu une incidence sur le lien entre les hospitalisations et la gravité de la fragilité. Le score CFS est une mesure subjective. Il est possible que les cliniciens évaluent différemment la gravité de la fragilité ou classent les patients de façon erronée en raison d'une disponibilité limitée. CONCLUSION: Chez les patients dialysés, une plus grande fragilité, telle que définie par le score CFS, a été associée à la fois à un risque accru d'être hospitalisé sur une plus longue durée cumulative et à un risque conjoint d'hospitalization et de décès.

Universal access to genetic counseling for women with epithelial ovarian cancer in Nova Scotia: Evaluating a new collaborative care model.

Women with pathogenic variants in BRCA1/2 have a significantly increased lifetime risk of breast and ovarian cancers. The availability of genetic testing to identify BRCA1/2 carriers is imperative to disease prevention and treatment. We evaluated the effectiveness of a new collaborative care model in Nova Scotia, involving the integration of genetic counselors into tumor board rounds, reduction in time allotted for initial genetic counseling appointments from 60 to 45 min, and a standardized dictation template, to increase referral rate for genetic counseling. We also assessed the study cohorts' preferences on timing for genetic testing. A retrospective chart review was performed on all women diagnosed with epithelial ovarian cancer (EOC) from 2012 to 2017 (N = 386). Pertinent clinical outcomes were categorized and wait times to different nodes of the clinical pathway assessed. A questionnaire was sent to this same cohort of women to identify preference for the timing of genetic testing (n = 103). The chi-square and Wilcoxon's rank-sum tests were used to compare demographic and clinical variables pre- and post-care model implementation. We identified a 48.2% (95% CI: 39.4-56.7, p < .001) increase in referral for genetic counseling following implementation of the new care model. Median time from diagnosis to referral decreased by 74.0 days (p < .001) and median time from referral to first appointment by 54.0 days (p < .001). 56.3% of women desired referral at the time of diagnosis. This care model for women newly diagnosed with EOC in Nova Scotia was successful in increasing referral rates for genetic counseling. Majority of women pursued genetic testing following and favored that referral for genetic counseling be made at the time of diagnosis, highlighting the importance for timely access.

Tumor levels of the mediators of ErbB2-driven anoikis resistance correlate with breast cancer relapse in patients receiving trastuzumab-based therapies.

PURPOSE: Patients with ErbB2/Her2 oncoprotein-positive breast cancers often receive neoadjuvant therapies (NATs) containing the anti-ErbB2 antibody trastuzumab. Tumors that are still present after NATs are resected, and patients continue receiving trastuzumab. These cancers are associated with high relapse risk. Whether relapse will occur cannot be presently reliably predicted. The ability to make such predictions could improve disease management. We found previously that ErbB2 blocks breast tumor cell anoikis, apoptosis induced by cell detachment from the extracellular matrix, by downregulating the pro-apoptotic protein Irf6 and upregulating the anti-apoptotic protein Epidermal Growth Factor Receptor (EGFR) in the cells and, thus, promotes their three-dimensional growth. We now tested whether tumor levels of these proteins before and after NATs correlate with patients' relapse-free survival (RFS) and overall survival (OS). METHODS: We selected archival breast tumor samples collected from 37 women with ErbB2-positive stages II and III breast cancer before and after NATs. We used immunohistochemistry to test whether levels of the indicated proteins in respective tumors correlate with RFS and OS. RESULTS: We observed that the presence of high Irf6 levels in the tumors following NATs correlated with reduced RFS and OS. Perhaps not by coincidence, we noticed that trastuzumab-sensitive ErbB2-positive breast cancer cells selected for the ability to overproduce exogenous Irf6 in culture acquired trastuzumab resistance. Finally, EGFR presence in patients' tumors before or after NATs was associated with decreased RFS and OS. CONCLUSIONS: This study could help identify patients with ErbB2-positive tumors that are at increased risk of disease relapse following NATs.

Understanding the effects of reductionist biological views of eating disorder etiology on patient attitudes and behavior.

While eating disorders were historically considered to be a result of psychological or environmental causes, current evidence suggests that eating disorders are the product of complex gene-environment interactions wherein heritable vulnerabilities are activated by multiple exposures to environmental stimuli over the lifespan. Despite the fact that this integrated biopsychosocial etiological view of eating disorders is accepted among many professionals in the eating disorder field, evidence suggests that the general public and some clinicians are susceptible to dualist, or reductionist, views of psychopathology. Currently, little is known about (a) the prevalence of reductionist biological views of eating disorder etiology in those with eating disorders (this view attributes the cause of eating disorders to predominantly biological factors but does not acknowledge psychosocial factors as important contributors), (b) the effects of reductionist biological views on clinical outcomes, and (c) the most effective methods for modifying these views. In this article, we present the results of a preliminary investigation on the relationship between perceived causes of eating disorders and the attitudes and behaviors of those with eating disorders. We then go on to propose specific avenues for further research on uncovering the effects of reductionist biological views of eating disorder etiology.

The use of noninvasive imaging techniques in the diagnosis of melanoma: a prospective diagnostic accuracy study.

BACKGROUND: Early detection of melanoma is crucial to improving the detection of thin curable melanomas. Noninvasive, computer-assisted methods have been developed to use at the bedside to aid in diagnoses but have not been compared directly in a clinical setting. OBJECTIVE: We conducted a prospective diagnostic accuracy study comparing a dermatologist's clinical examination at the bedside, teledermatology, and noninvasive imaging techniques (FotoFinder, MelaFind, and Verisante Aura). METHODS: A total of 184 patients were recruited prospectively from an outpatient dermatology clinic, with lesions imaged, assessed, and excised. Skin specimens were assessed by 2 blinded pathologists, providing the gold standard comparison. RESULTS: Fifty-nine lesions from 56 patients had a histopathologic diagnosis of melanoma, whereas 150 lesions from 128 patients were diagnosed as benign. Sensitivities and specificities were, respectively, MelaFind (82.5%, 52.4%), Verisante Aura (21.4%, 86.2%), and FotoFinder Moleanalyzer Pro (88.1%, 78.8%). The sensitivity and specificity of the teledermoscopist (84.5% and 82.6%, respectively) and local dermatologist (96.6% and 32.2%, respectively) were also compared. LIMITATIONS: There are inherent limitations in using pathology as the gold standard to compare sensitivities and specificities. CONCLUSION: This study demonstrates that the highest sensitivity and specificity of the instruments were established with the FotoFinder Moleanalyzer Pro, which could be a valuable tool to assist with, but not replace, clinical decision making.

A virtual platform to deliver ambulatory care for patients with atrial fibrillation.

Background: There are little data on the use of virtual care for patients with arrhythmia. We evaluated a virtual clinic platform, in conjunction with specialist care, for patients with symptomatic atrial fibrillation (AF). Methods: This was a prospective, observational cohort study evaluating an online educational and treatment platform, with a randomized sub-study examining the use of an ambulatory single-lead electrocardiogram heart monitor (AHM). Follow-up was 6 months. The main outcome was patients' platform use; success was defined as 90% of patients using the platform at least once, and 75% using it at least twice. The primary outcome in the AHM sub-study was Atrial Fibrillation Symptom Severity (AFSS) score. Other outcomes included patient satisfaction questionnaires, quality of life, emergency department visits, and hospitalizations for AF. Results: We enrolled 94 patients between July 2018 and May 2019; 83% of patients logged in at least once and 54.3% more than once. Patients who were older, were male, or had new-onset AF were more likely to log in to the platform. Satisfaction scores were high; 70%-94% of patients responded favorably. Quality-of-life scores improved at 3 and 6 months. In the AHM sub-study (n = 71), those who received an AHM had lower AFSS scores (least square mean difference -2.52, 95% CI -4.48 to -0.25, P = .03). There was no difference in emergency department visits or hospitalizations. Conclusion: The online platform did not reach our feasibility target but was well received. Allocation of an AHM was associated with improved quality of life. Virtual AF care shows promise and should be evaluated in further research.

Blood-brain barrier leakage in systemic lupus erythematosus is associated with gray matter loss and cognitive impairment.

OBJECTIVES: To examine the association between blood-brain barrier (BBB) integrity, brain volume and cognitive dysfunction in adult patients with systemic lupus erythematosus (SLE). METHODS: A total of 65 ambulatory patients with SLE and 9 healthy controls underwent dynamic contrast-enhanced MRI scanning, for quantitative assessment of BBB permeability. Volumetric data were extracted using the VolBrain pipeline. Global cognitive function was evaluated using a screening battery consisting of tasks falling into five broad cognitive domains, and was compared between patients with normal versus extensive BBB leakage. RESULTS: Patients with SLE had significantly higher levels of BBB leakage compared with controls (p=0.04). Extensive BBB leakage (affecting over >9% of brain volume) was identified only in patients with SLE (16/65; 24.6%), who also had smaller right and left cerebral grey matter volumes compared with controls (p=0.04). Extensive BBB leakage was associated with lower global cognitive scores (p=0.02), and with the presence of impairment on one or more cognitive tasks (p=0.01). CONCLUSION: Our findings provide evidence for a link between extensive BBB leakage and changes in both brain structure and cognitive function in patients with SLE. Future studies should investigate the mechanisms underlying BBB-mediated cognitive impairment, validate the diagnostic utility of BBB imaging, and determine the potential of targeting the BBB as a therapeutic strategy in patients with SLE.

Outcomes of a Provincial Myocardial Infarction Reperfusion Strategy: A Population-Based, Retrospective Cohort Study.

BACKGROUND: Fibrinolysis is an acceptable treatment for acute ST-segment elevation myocardial infarction (STEMI) when primary percutaneous coronary intervention (PCI) cannot be performed within 120 minutes. The American Heart Association has recommended Emergency Medical Services (EMS) interventions such as prehospital fibrinolysis (PHF), prehospital electrocardiogram (ECG), and hospital bypass direct to PCI center. Nova Scotia, Canada has incorporated these interventions into a unique province-wide approach to STEMI care. A retrospective cohort analysis comparing the primary outcome of 30-day mortality for patients receiving either prehospital or emergency department (ED) fibrinolysis (EDF) to patients transported directly by EMS from community or regional ED for primary PCI was conducted. METHODS: This retrospective, population-based cohort study included all STEMI patients in Nova Scotia who survived to hospital admission from July 2011 through July 2013. Three provincial databases were used to collect demographic, 30-day mortality, hospital readmission, and rescue PCI data. The results were grouped and compared according to reperfusion strategy received: PHF, EDF, patients brought by ambulance via EMS direct to PCI (EMS to PCI), and ED to PCI (ED to PCI). RESULTS: There were 1,071 STEMI patients included with 145 PHF, 606 EDF, 98 EMS to PCI, and 222 ED to PCI. There were no significant differences in 30-day mortality across groups (n, %): PHF 5(3); EDF 36(6); EHS to PCI <5(2); and ED to PCI 10(4); P = .28. There was no significant difference in patients receiving fibrinolysis who underwent rescue PCI. CONCLUSIONS: Prehospital fibrinolysis incorporated into a province-wide approach to STEMI treatment is feasible with no observed difference in patient 30-day mortality outcomes observed.