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.

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.

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.

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.

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.

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.

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.

Low-grade serous carcinoma (LGSC): A Canadian multicenter review of practice patterns and patient outcomes.

OBJECTIVE: Patients with advanced low-grade serous carcinoma (LGSC) have poor long-term survival rates. As a rare histotype, there are uncertainties regarding the use of current therapies. Thus, we studied practice patterns and treatment outcomes as part of a national initiative to better understand and improve the care of women with advanced LGSC. METHODS: This retrospective cohort study was conducted in 5 Canadian referral institutions from 2000 to 2016. Data collection and pathology reporting were standardized. Outcome measures included overall survival (OS), progression-free survival (PFS), progression-free intervals (PFI), and time to next treatment (TTNT). Cox regression analysis was used to evaluate the effects of clinical and pathologic factors on outcomes and prognosis. RESULTS: There were 134 patients (stage II-IV) with a median follow-up of 32.4 months (range 1.6-228). Four primary treatments were compared across institutions: 1) surgery followed by chemotherapy (56%), 2) neoadjuvant chemotherapy (NACT) followed by surgery (27%), 3) surgery alone (9%), and 4) surgery followed by anti-hormone therapy (4%). Primary platinum/paclitaxel chemotherapy was used in 81%. Patients treated with NACT had worse PFS. Multivariable Cox regression analysis identified lesser residual disease, younger age, and primary peritoneal origin as variables significantly associated with better OS/PFS (p < 0.03). One institution had significantly better PFS than the others (p = 0.025), but this finding could be related to a higher frequency of primary peritoneal LGSC. PFI and TTNT intervals in patients with relapsed disease were not significantly different after the first relapse irrespective of treatment type. CONCLUSIONS: There are notable differences in practice patterns across Canada. This underscores the need for ongoing strategies to measure, evaluate and achieve optimal patient outcomes for women with advanced LGSC.

Case-Control Study of Endovascular Thrombectomy in a Canadian Stroke Center.

BACKGROUND: Although the efficacy of endovascular thrombectomy (EVT) for acute ischemic stroke caused by intracranial anterior circulation large vessel occlusion (LVO) is proven, demonstration of local effectiveness is critical for health system planning and resource allocation because of the complexity and cost of this treatment. METHODS: Using our prospective registry, we identified all patients who underwent EVT for out-of-hospital LVO stroke from February 1, 2013 through January 31, 2017 (n = 44), and matched them 1:1 in a hierarchical fashion with control patients not treated with EVT based on age (±5 years), prehospital functional status, stroke syndrome, severity, and thrombolysis administration. Demographics, in-hospital mortality, discharge disposition from acute care, length of hospitalization, and functional status at discharge from acute care and at follow-up were compared between cases and controls. RESULTS: For EVT-treated patients (median age 66, 50% women), the median onset-to-recanalization interval was 247 min, and successful recanalization was achieved in 30/44 (91%). Alteplase was administered in 75% of cases and 57% of controls (p = 0.07). In-hospital mortality was 11% among the cases and 36% in the control group (p = 0.006); this survival benefit persisted during follow-up (p = 0.014). More EVT patients were discharged home from acute care (50% vs. 18%, p = 0.002). Among survivors, there were nonsignificant trends in favor of EVT for median length of hospitalization (14 vs. 41 days, p = 0.11) and functional independence at follow-up (51% vs. 32%, p = 0.079). CONCLUSION: EVT improved survival and decreased disability. This demonstration of single-center effectiveness may help facilitate expansion of EVT services in similar health-care jurisdictions.

Étude cas-témoin portant sur la thrombectomie endovasculaire dans un centre canadien de prise en charge des AVC. Contexte : Bien qu'on ait prouvé l'efficacité de la thrombectomie endovasculaire dans le cas d'accidents ischémiques cérébraux aigus causés par l'occlusion de grosses artères affectant la circulation antérieure intracrânienne, la démonstration de son efficacité sur le terrain est essentielle à la planification du réseau la santé et à l'allocation des ressources en raison de la complexité de ce traitement et des coûts qui y sont associés. Méthodes : À l'aide d'un registre prospectif, nous avons identifié tous les patients ayant bénéficié (n = 44), du 1er février 2013 au 31 janvier 2017, d'une thrombectomie endovasculaire à la suite d'un AVC survenu en dehors d'un établissement de la santé, AVC causé par l'occlusion de grosses artères. De manière hiérarchique, nous avons fait correspondre nos patients dans un rapport de 1 à 1 à nos témoins non traités par thrombectomie endovasculaire, et ce, en nous basant sur leur âge (± 5 ans), sur leur situation fonctionnelle avant d'être admis, sur les signes cliniques et la gravité de leur AVC, et sur l'administration d'un traitement thrombolytique. Nous avons également comparé leurs caractéristiques démographiques, leur taux de mortalité hospitalière, les modalités d'obtention d'un congé des soins intensifs, la durée de leur hospitalisation et leur situation fonctionnelle au moment de quitter les soins intensifs et à l'occasion d'un suivi. Résultats : Dans le cas de nos patients traités par thrombectomie endovasculaire (âge médian : 66 ans ; 50 % de femmes), l'intervalle médian entre les premiers signes d'un AVC et la recanalisation a été de 247 minutes. Fait à souligner, une recanalisation réussie a été accomplie dans 30 cas sur 44 (91 %). L'altéplase a été administré dans 75 % des cas et chez 57 % des témoins (p = 0,07). En ce qui concerne le taux de mortalité hospitalière, il a été de 11 % parmi tous nos cas et de 36 % chez nos témoins (p = 0,006) ; À noter que cet avantage en termes de survie a persisté au moment des suivis (p = 0,014). Plus de patients traités par thrombectomie endovasculaire ont obtenu leur congé des soins intensifs et sont revenus à la maison (50 % contre 18 % ; p = 0,002). Parmi les survivants à ces AVC, on a noté des tendances non significatives en faveur des patients traités par thrombectomie endovasculaire pour ce qui est de la durée médiane d'hospitalisation (14 jours contre 41 jours ; p = 0,11) et de l'autonomie fonctionnelle au moment des suivis (51 % contre 32 % ; p = 0,079). Conclusion : En somme, la thrombectomie endovasculaire a permis d'améliorer le taux de survie des patients ainsi que leur niveau d'autonomie fonctionnelle. Effectuée dans un seul établissement hospitalier, cette démonstration de l'efficacité de ce traitement pourrait contribuer à faciliter l'essor des traitements de thrombectomie endovasculaire dans d'autres systèmes de santé similaires.

Efficacy of Intrathecal Fentanyl for Cesarean Delivery: A Systematic Review and Meta-analysis of Randomized Controlled Trials With Trial Sequential Analysis.

BACKGROUND: Fentanyl and morphine are the 2 most commonly added opioids to bupivacaine for spinal anesthesia during cesarean delivery. Numerous clinical trials have assessed efficacy and safety of different doses of fentanyl added to intrathecal bupivacaine for spinal anesthesia, yet its benefit, harm, and optimal dose remain unclear. This study aimed to systematically review the evidence of the efficacy of fentanyl when added to intrathecal bupivacaine alone and when added to bupivacaine with morphine for spinal anesthesia during cesarean delivery. METHODS: Key electronic databases (PubMed, Embase, and Cochrane Library) were searched for randomized controlled trials in the cesarean delivery population. The primary outcome was the failure rate of spinal anesthesia, as assessed by the need for either conversion to general anesthesia or intraoperative analgesic supplementation. Two reviewers independently extracted the data using a standardized electronic form. Results are expressed as relative risks or mean differences with 95% CIs. RESULTS: Seventeen randomized controlled clinical trials (most judged as low or unclear risk of bias) with 1064 participants provided data for the meta-analysis. Fentanyl added to intrathecal bupivacaine alone reduced the need for intraoperative supplemental analgesia (relative risk, 0.18; 95% CI, 0.11-0.27; number needed to treat, 4) and the incidence of nausea/vomiting (relative risk, 0.41; 95% CI, 0.24-0.70; number needed to treat, 6.5), with longer time to first postoperative analgesia request (mean difference, 91 minutes; 95% CI, 69-113). No difference was observed regarding the need for conversion to general anesthesia (relative risk, 0.67; 95% CI, 0.12-3.57), the incidence of hypotension, the onset of sensory block, or the duration of motor block. However, the addition of intrathecal fentanyl was associated with higher incidence of intraoperative pruritus (relative risk, 5.89; 95% CI, 2.07-16.79; number needed to harm, 13.5). The inclusion of fentanyl to intrathecal bupivacaine-morphine compared to intrathecal bupivacaine-morphine alone conferred a similar benefit, with a significantly reduced need for intraoperative supplemental analgesia (relative risk, 0.16; 95% CI, 0.03-0.95; number needed to treat, 9). Analysis using a funnel plot indicated a possibility of publication bias in included studies. CONCLUSIONS: Current evidence suggests a benefit of using fentanyl as both an additive to intrathecal bupivacaine alone and to intrathecal bupivacaine combined with morphine for cesarean delivery under spinal anesthesia. The possibility of publication bias, small sample size, and high risk of bias in some of the included studies warrant treating the results with caution.

A Retrospective Study of the Clinical Characteristics Associated with Alcohol and Cannabis use in Early Phase Psychosis.

OBJECTIVE: Alcohol and cannabis misuse are common in patients with early phase psychosis (EPP); however, research has tended to focus primarily on cannabis misuse and EPP outcomes, with a relative lack of data on alcohol misuse. This retrospective cross-sectional EPP study investigated the relationship between cannabis, alcohol, and cannabis combined with alcohol misuse, on age, gender, psychotic, depressive and anxiety symptom severity, and social/occupational functioning, at entry to service. METHODS: Two-hundred and sixty-four EPP patients were divided into 4 groups based on substance use measured by the Alcohol, Smoking and Substance Involvement Screening Test: (1) no to low-level cannabis and alcohol misuse (LU), (2) moderate to high alcohol misuse only (AU), (3) moderate to high cannabis misuse only (CU), and (4) moderate to high alcohol and cannabis misuse (AU + CU). RESULTS: We found significant between group differences in age (with the AU group being the oldest and AU + CU group the youngest) as well as gender (with the CU group having the highest percentage of men). There were also group differences in positive psychotic symptoms (lowest in AU group), trait anxiety (highest in AU + CU group), and social/occupational functioning (highest in AU group). Further regression analyses revealed a particularly strong relationship between AU + CU group and trait anxiety (3-fold increased odds of clinical trait anxiety for combined misuse of alcohol and cannabis compared to non/low users). CONCLUSIONS: This study demonstrates the unique demographic and clinical characteristics found in the EPP population at entry to care associated with alcohol and cannabis misuse both separately and in combination. This work highlights the importance of including the assessment of alcohol misuse in addition to cannabis misuse in future treatment guidelines and research.

Apocrine Hidradenoma and Adenomyoepithelioma: Entities on a Biological Continuum of Adnexal Neoplasia.

Apocrine hidradenomas (AH) once believed to harbor myoepithelial cells are now considered pure epithelial neoplasms. They are categorized separately from adenomyoepitheliomas which consist of apocrine epithelial and myoepithelial components. Reports of myoepithelial tumors arising in AH have suggested a link between the 2. Our goal was to explore whether cases diagnosed on routine microscopy as AH harbored occult myoepithelial elements, which would be disclosed by an immunohistochemical evaluation. Twenty-nine such cases, derived from a teaching collection of one of the authors, formed the basis of the study. Clinical and demographic data were documented, and morphological details of the cases were recorded. A panel of immunohistochemistry (AE1AE3, CK8/18, epithelial membrane antigen, p63, S100 protein, glial fibrillary acid protein, calponin, alpha actin, and others), designed to identify myoepithelial cells, was used. The population consisted of 14 women and 15 men (mean age 55.8; range 26-82 years). The tumors, located on the head/neck (14), limbs (10), and trunk (5), were solid (2) and solid/cystic (27). They exhibited varied (often combined) cytological elements (clear, squamoid, polygonal, and mucinous cells). On immunohistochemistry, aggregates of myoepithelial cells were identified in 5 (17%) cases. Four were calponin+ and AE1AE3+; they occupied ≤30% of tumor volumes and exhibited fusiform cytomorphology. One was S100 protein+ and AE1AE3+; it occupied 70% of tumor volume and exhibited polygonal cytomorphology. The gradation in the volume of myoepithelial elements disclosed by immunohistochemistry in a subset of our cases suggests that AH and adenomyoepitheliomas exist on a biological continuum of adnexal neoplasia. The diagnostic categorization of lesions with dual elements requires further study, but we propose that the term adenomyoepithelioma be restricted to those in which myoepithelial cells constitute ≥25% of tumor volume.

The clinical utility of baseline cardiac assessments prior to adjuvant anthracycline chemotherapy in breast cancer: a systematic review and meta-analysis.

BACKGROUND: Cardiac assessment with multi-gated acquisition scan (MUGA) or echocardiography (ECHO) is commonly employed prior to adjuvant anthracycline-based chemotherapy (AA). However, the clinical utility of routine baseline cardiac assessments prior to AA for early-stage breast cancer (EBC) is unknown. OBJECTIVES: To determine: (i) the clinical utility of routine baseline cardiac assessments prior to AA for EBC and (ii) identify patients in whom baseline cardiac assessments may not be warranted. METHODS: A systematic review of the literature was conducted to identify all relevant studies that met predefined criteria. The clinical utility was defined by: (i) the rates of abnormal baseline left ventricular ejection fraction (LVEF) and (ii) the rates of change in chemotherapy decisions prompted by baseline LVEF results. RESULTS: Eight studies met our criteria, of whom six (n = 2545) reported rates of abnormal LVEF and six (n = 1713) reported rates of change in chemotherapy decision. Overall, 2.5% (95% CI 2.0-4.0%) of patients had abnormal baseline LVEF and 1.6% (95% CI 1.0-3.0%) had a change in chemotherapy decision. In subset analyses, the underlying imaging modality (ECHO vs. MUGA) or inclusion of patients with metastatic disease (YES vs. NO) did not significantly affect these rates. There were no consistently identified underlying predictors of abnormal baseline LVEF across studies. CONCLUSIONS: Routine baseline cardiac assessments prior to AA in all EBC patients have low yield and infrequently affect clinical management. Future studies should further examine potential predictors of abnormal cardiac functions in an attempt to identify low risk patients in whom routine baseline LVEF assessment may not be warranted and prevent delay in chemotherapy administration.

Extended Duration of Active Surveillance of Small Renal Masses: A Prospective Cohort Study.

PURPOSE: We report the natural history of small renal masses in patients undergoing active surveillance with extended followup. MATERIALS AND METHODS: We performed a prospective cohort study in patients undergoing active surveillance of small renal masses diagnosed between 2001 and 2011 at a single institution. All patients underwent active surveillance of small renal masses presumed to be renal cell carcinoma based on diagnostic imaging. Reported patient outcomes included progression to treatment, metastatic disease and/or death. Linear and volumetric tumor growth rates were evaluated. RESULTS: Included in study were 103 patients with a total of 107 small renal masses. Median followup was 55.5 months in patients who continued on active surveillance. Median maximum diameter and volume at diagnosis were 2.1 cm (IQR 1.5-2.7) and 4.8 cm3 (IQR 1.7-11.9), respectively. At last followup 53 patients (51.5%) were alive without metastatic disease, 48 (45.6%) had died of another cause and metastatic disease had developed in 2 (1.9%), including 1 (1.0%) who ultimately died of metastatic renal cell carcinoma. The mean ± SEM linear and volumetric growth rates of all small renal masses were 0.21 ± 0.03 cm per year and 6.15 ± 2.15 cm3, respectively. Study limitations include nonstandardized followup and a lack of biopsy data on most patients. CONCLUSIONS: During extended followup the majority of small renal masses in patients on active surveillance display indolent behavior. The risk of progression to metastatic disease remains low.

Filaggrin gene loss-of-function mutations constitute a factor in patients with multiple contact allergies.

BACKGROUND: Polysensitivity is defined as three or more positive patch test reactions. The role of filaggrin gene (FLG) loss-of-function mutations in patients with polysensitivity has not been studied when barrier bypass and possible preceding barrier damage have been excluded. OBJECTIVES: To determine whether FLG loss of function mutations play a role in patients with multiple contact sensitivities when barrier bypass is excluded. METHODS: One hundred and sixty-nine patients with three or more, non-cross-reacting, positive patch test reactions were prospectively enrolled in this study. Exclusion criteria were a history of hand dermatitis, nickel and metal implants, and stasis dermatitis. Subjects were patch tested with the North American extended patch test series, and with other relevant haptens. DNA was obtained and sequenced for the following FLG loss-of-function mutations: R501X, 2282del4, R2447X, and S3247X. RESULTS: One hundred and sixty-five patients were genotyped for the four FLG mutations. There was a significant association between R501X mutation and polysensitivity. For the other three tested mutations, there were no significant associations with polysensitivity. When all mutations were combined, there was a significant association between loss-of-function FLG mutations and polysensitivity in patients with a history of atopic dermatitis. CONCLUSION: When skin barrier bypass is excluded, there is a significant association between polysensitivity and FLG loss-of-function mutations.

Extent to Which Caregivers Enhance the Wheelchair Skills Capacity and Confidence of Power Wheelchair Users: A Cross-Sectional Study.

OBJECTIVE: To test the hypothesis that caregivers enhance the wheelchair skills capacity and confidence of the power wheelchair users to whom they provide assistance, and to describe the nature of that assistance. DESIGN: Multicenter cross-sectional study. SETTING: Rehabilitation centers and communities. PARTICIPANTS: Participants (N=152) included caregivers (n=76) and wheelchair users (n=76). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Version 4.3 of the Wheelchair Skills Test (WST) and the Wheelchair Skills Test-Questionnaire (WST-Q). For each of the 30 individual skills, we recorded data about the wheelchair user alone and in combination (blended) with the caregiver. RESULTS: The mean total WST capacity scores ± SD for the wheelchair users alone and blended were 78.1%±9.3% and 92.4%±6.1%, respectively, with a mean difference of 14.3%±8.7% (P<.0001). The mean WST-Q capacity scores ± SD were 77.0%±10.6% and 93.2%±6.4%, respectively, with a mean difference of 16.3%±9.8% (P<.0001). The mean WST-Q confidence scores ± SD were 75.5%±12.7% and 92.8%±6.8%, respectively, with a mean difference of 17.5%±11.7% (P<.0001). The mean differences corresponded to relative improvements of 18.3%, 21.0%, and 22.9%, respectively. The nature and benefits of the caregivers' assistance could be summarized in 7 themes (eg, caregiver provides verbal support [cueing, coaching, reporting about the environment]). CONCLUSIONS: Caregivers significantly enhance the wheelchair skills capacity and confidence of the power wheelchair users to whom they provide assistance, and they do so in a variety of ways. These findings have significance for wheelchair skills assessment and training.

Antipsychotic Drug Dispensations in Older Adults, Including Continuation After a Fall-Related Hospitalization: Identifying Adherence to Screening Tool of Older Persons' Potentially Inappropriate Prescriptions Criteria Using the Nova Scotia Seniors' Pharmacare Program and Canadian Institute for Health's Discharge Databases.

PURPOSE: Despite well-established concerns regarding adverse drug effects, antipsychotics are frequently prescribed for older adults. Our first objective was to identify trends in antipsychotic dispensations to older Nova Scotians. STOPP (Screening Tool of Older Persons' Potentially Inappropriate Prescriptions) criteria identify antipsychotic use in those with a history of falls as potentially inappropriate. Our second objective was to identify trends, predictors, and adherence with this STOPP criteria by identifying continued antipsychotic dispensations following a fall-related hospitalization. METHODS: A descriptive cross-sectional cohort study of Nova Scotia Seniors' Pharmacare Program (NSSPP) beneficiaries ≥ 66 years with at least one antipsychotic dispensation annually from April 1, 2009 to March 31, 2014 was completed. As well, unique beneficiaries with at least one antipsychotic dispensation in the four-year period between April 1, 2009 and March 31, 2013 were linked to fall-related hospitalizations recorded in the Canadian Institute for Health Information Discharge Abstract Database. The relationship of age, sex, fiscal year, days supply and length-of-stay were studied to identify predictors of continued antipsychotic dispensation post-discharge. Descriptive statistics and multivariate logistic analysis were performed. Odds ratios for the association of risk factors and adherence to STOPP criteria were calculated. FINDINGS: We identified that in each year observed, there were 6% of eligible NSSPP beneficiaries that received at least one antipsychotic dispensation. Approximately 70% of antipsychotic dispensations were for second generation agents, primarily quetiapine and risperidone. Of the unique beneficiaries with at least one antipsychotic dispensation in the four-year period between April 1, 2009 and March 31, 2013 who survived a fall-related hospitalization over 75% were dispensed an antipsychotic in the 100 days following hospital discharge. Logistic regression showed no statistically significant association between potentially inappropriate therapy and potential predictors in multivariate analysis. IMPLICATIONS: In each year from 2009 to 2014, 6% of Nova Scotia Seniors' Pharmacare beneficiaries were dispensed at least one antipsychotic prescription. Over 75% of the older adults who received an antipsychotic dispensation in the 100 days prior to a fall-related hospitalization, continued the drug class after discharge. This demonstrates that despite the recommendations of quality indicators such as the STOPP criteria, antipsychotics are continued in individuals at a high risk of falling. Future investigations are needed to inform health team, system, and policy interventions to improve concordance with this antipsychotic specific STOPP criterion when appropriate.