Effect of Aerobic Exercise on Symptom Burden and Quality of Life in Adults with Persisting Post-Concussive Symptoms: The ACTBI Randomized Clinical Trial.

OBJECTIVE: To evaluate a 6-week sub-symptom threshold aerobic exercise protocol (AEP) vs a stretching protocol (SP) on symptom burden and quality of life (QoL) in adults with persisting post-concussive symptoms (PPCS). DESIGN: The Aerobic exercise for treatment of Chronic symptoms following mild Traumatic Brain Injury (ACTBI) Trial was a randomized controlled trial with two groups. SETTING: Outpatient brain injury, pain and physiotherapy clinics. PARTICIPANTS: A total of 210 participants were screened. A consecutive sample of 52 adults with PPCS and exercise intolerance following mild traumatic brain injury were enrolled. No participants withdrew due to adverse effects of intervention. INTERVENTIONS: Participants were randomized to a 6-week AEP (n=27) or 6-week SP (n=25). MAIN OUTCOMES AND MEASURES: The Rivermead Post Concussion Symptoms Questionnaire (RPQ) was the primary outcome. Secondary outcomes included QoL using the Quality of Life After Brain Injury Questionnaire (QOLIBRI), in addition to measures of mood, anxiety, functional impact of headache, fatigue, dizziness, exercise tolerance and sleep. RESULTS: Participants were a mean (SD) of 43.0 (10.9) years old (75% female) and 24.7 (14.0) months post-injury. In per protocol analysis, between group difference (AEP vs SP) was not significant for RPQ, but QOLIBRI between group difference was significant (mean change=5.024, 95% Cl [0.057, 9.992], p=0.047) from baseline to 6-weeks. In intention to treat analysis, between group change in primary and secondary outcomes were not significant. CONCLUSIONS: This trial provides preliminary data to support prescription of aerobic exercise for adults with PPCS. Despite presenting with exercise intolerance, participants were able to engage in sub-symptom threshold exercise with QoL benefits.

Variations in care of neonates during therapeutic hypothermia: call for care practice bundle implementation.

BACKGROUND: Therapeutic hypothermia (TH) is the gold-standard treatment for moderate and severe neonatal encephalopathy (NE). Care during TH has implications for long-term outcomes. Outcome variability exists among neonatal intensive care units (NICUs) in Canada, but care variations are not understood well. This study examines variations in care practices for neonates with NE treated with TH in NICUs across Canada. METHODS: A non-anonymous, web-based questionnaire was emailed to tertiary NICUs in Canada providing TH for NE to assess care practices during the first days of life and neurodevelopmental follow-up. RESULTS: Ninety-two percent (24/26) responded. Centres followed national guidelines regarding the use of the modified Sarnat score to assess the initial severity of NE, the need to initiate TH within the first 6 h of birth, and the importance of follow-up. However, other practices varied, including ventilation mode, definition/treatment of hypotension, routine echocardiography, use of sedation, use of electroencephalogram (EEG), MRI timing, placental analysis, and follow-up duration. CONCLUSIONS: NICUs across Canada follow available national guidelines, but variations exist in practices for managing NE during TH. Development and implementation of a consensus-based care bundle for neonates during TH may reduce practice variability and improve outcomes. IMPACT: This survey describes the current HIE care practices and variation among tertiary centres in Canada. Variations exist in the care of neonates with NE treated with TH in NICUs across Canada. This paper Identifies areas of variation that are not discussed in detail in the national guidelines and will help to set up quality improvement initiatives. Elucidating the variation in care practices calls for the creation and implementation of a national, consensus-based care bundle, with the objective to improve the outcomes of these critically ill neonates.

New insights into visually impaired patients' preferred reading illumination and home-based reading speed with new task-lighting.

INTRODUCTION: When optimal lighting is applied to hard-copy materials for visually impaired individuals, laboratory-based reading performance can improve significantly. However, it is not known whether their lighting preferences are related to ocular factors or if laboratory-based reading improvements will translate to home-based environments. METHODS: Preferences for brightness (lux) and colour temperature (degrees Kelvin; K) with the LuxIQ/2 for 'most comfort' while reading at near were evaluated in-clinic for 71 adults with ocular disease affecting the outer (n = 37; 52%), inner or all retinal layers (n = 34; 48%). Twenty participants received either an OttLite Cobra lamp or a generic gooseneck lamp with a bulb resembling LuxIQ/2 parameters for their preferred reading light, and then completed home-based telephone evaluations using the sustained silent reading test. RESULTS: Participants with outer retinal disease preferred significantly brighter light intensity by an average of 838 lux versus those with inner retinal disease (95% CI: 331, 1344; p = 0.002). No participants opted for a coloured tint for reading based on the LuxIQ/2 measurements since they preferred white light only; most preferred the OttLite Cobra lamp. At home, reading speed improved significantly by an average of 37 words per minute with the new lamp (95% CI: 12, 62; p = 0.005). CONCLUSIONS: Patients with outer retinal disease prefered brighter light intensity for reading. Clinic-based lighting preferences yielded improvements in reading speed when using a new task light at home.

Atypical Exophytic Retinal Capillary Hemangioma and Diagnostic Modalities.

PURPOSE: Retinal capillary hemangioma (RCH) can occur in isolation or may be associated with von Hippel-Lindau disease. The classic RCH is described as a globular reddish lesion with a dilated feeding artery and a tortuous draining vein, indicative of a common endophytic growth pattern. Exophytic patterns are far more rare and, because of its subtle appearance, often missed or misdiagnosed. CASE REPORT: A 24-year-old woman presented with complaints of a mid-peripheral superior field defect OS. She had no family history of von Hippel-Lindau disease. Best-corrected visual acuity was 20/20 OD, OS. Dilated fundus examination of the left eye revealed a peripheral large inferotemporal retinal lesion with an overlying vascular network. Corresponding feeding and draining vasculature was not clearly noted on dilated fundus examination. Optical coherence tomography, ultrasonography, and fluorescein angiography testing were used to confirm the diagnosis of an exophytic peripheral RCH. Anti-vascular endothelial growth factor injections and cryotherapy were initiated, and the patient was scheduled for radioactive plaque brachytherapy. Genetic testing and proper scans were also recommended. CONCLUSIONS: This case illustrates an atypical exophytic peripheral RCH, rarely reported in the literature. The utilization of a variety of diagnostic modalities was highly effective, aiding in the diagnosis of this condition.

Assessment of sleep parameters in adults with persistent post-concussive symptoms.

OBJECTIVES: The primary aim of this study was to characterize sleep in adults with persistent post-concussive symptoms (PPCS). Secondary aims explored relationships between sleep parameters, injury characteristics, and symptom questionnaires. METHODS: This case-controlled, cross-sectional study recruited adults (18-65yrs) diagnosed with PPCS and age and sex-matched controls. Participants wore a wrist-worn actigraph for 3-7 nights and completed daily sleep diaries. Participants completed questionnaires examining daytime sleepiness, fatigue, anxiety/depressive symptoms, and sedentariness. Sleep parameters were compared between groups using Mann-Whitney U tests. Secondary analyses used two-way ANOVA and Spearman's rank correlations. RESULTS: Fifty adults with PPCS (43.7 ± 10.6yrs, 78 % female) and 50 controls (43.6 ± 11.0yrs) were included in this study. Adults with PPCS had significantly longer sleep onset latency (PPCS 16.99 ± 14.51min, Controls 8.87 ± 6.44min, p < 0.001) and total sleep time (PPCS 8.3 ± 1.0hrs, Control 7.6 ± 0.9hrs, p = 0.030) compared to controls, but woke up later (PPCS 7:57:27 ± 1:36:40, Control 7:17:16 ± 0:50:08, p = 0.026) and had poorer sleep efficiency (PPCS 77.9 ± 7.5 %, Control 80.8 ± 6.0 %, p = 0.019) than controls. Adults with PPCS reported more daytime sleepiness (Epworth Sleepiness Scale: PPCS 8.70 ± 4.61, Control 4.28 ± 2.79, p < 0.001) and fatigue (Fatigue Severity Scale: PPCS 56.54 ± 12.92, Control 21.90 ± 10.38, p < 0.001). Injury characteristics did not significantly affect sleep parameters in adults with PPCS. Actigraphy parameters were not significantly correlated to questionnaire measures. CONCLUSION: Several actigraphy sleep parameters were significantly altered in adults with PPCS compared to controls, but did not correlate with sleep questionnaires, suggesting both are useful tools in characterizing sleep in PPCS. Further, this study provides potential treatment targets to improve sleep difficulties in adults with PPCS.

Biophysical analysis of binding of WW domains of the YAP2 transcriptional regulator to PPXY motifs within WBP1 and WBP2 adaptors.

The YAP2 transcriptional regulator mediates a plethora of cellular functions, including the newly discovered Hippo tumor suppressor pathway, by virtue of its ability to recognize WBP1 and WBP2 signaling adaptors among a wide variety of other ligands. Herein, using isothermal titration calorimery and circular dichroism in combination with molecular modeling and molecular dynamics, we provide evidence that the WW1 and WW2 domains of YAP2 recognize various PPXY motifs within WBP1 and WBP2 in a highly promiscuous and subtle manner. Thus, although both WW domains strictly require the integrity of the consensus PPXY sequence, nonconsensus residues within and flanking this motif are not critical for high-affinity binding, implying that they most likely play a role in stabilizing the polyproline type II helical conformation of the PPXY ligands. Of particular interest is the observation that both WW domains bind to a PPXYXG motif with highest affinity, implicating a preference for a nonbulky and flexible glycine one residue to the C-terminal side of the consensus tyrosine. Importantly, a large set of residues within both WW domains and the PPXY motifs appear to undergo rapid fluctuations on a nanosecond time scale, suggesting that WW-ligand interactions are highly dynamic and that such conformational entropy may be an integral part of the reversible and temporal nature of cellular signaling cascades. Collectively, our study sheds light on the molecular determinants of a key WW-ligand interaction pertinent to cellular functions in health and disease.

Changing Behavior among Nurses to Track Indwelling Urinary Catheters in Hospitalized Patients.

Catheter-associated urinary tract infections (CAUTIs) are preventable complications of hospitalization. An interdisciplinary team developed a curriculum to increase awareness of the presence of indwelling urinary catheters (IUCs) in hospitalized patients, addressed practical, primarily nurse-controlled inpatient risk-reduction interventions, and promoted the use of the IUC labels ("tags"). Five thirty-minute educational sessions were cycled over three daily nursing shifts on two inpatient medical floors over a 1-year period; participants were surveyed (n = 152) to elicit feedback and provide real-time insight on the learning objectives. Nurse self-reported IUC tagging was early and sustained; after the IUC tag was introduced, there was a significant increase in tagging reported by the end of the block of educational sessions (from 46.2% to 84.6%, P = 0.001). Early engagement combined with a targeted educational initiative led to increased knowledge, changes in behavior, and renewed CAUTI awareness in hospitalized patients with IUCs. The processes employed in this small-scale project can be applied to broader, hospitalwide initiatives and to large-scale initiatives for healthcare interventions. As first-line providers with responsibility for the placement and daily maintenance of IUCs, nurses are ideally positioned to implement efforts addressing CAUTIs in the hospital setting.

First report of warfarin dose requirements in patients possessing the CYP2C9*12 allele.

BACKGROUND: Warfarin is the most frequently prescribed anticoagulant in North America and Europe. It is administered as a racemate, but S-warfarin is principally responsible for its anticoagulant activity. Cytochrome P450 (CYP) 2C9 is the enzyme primarily responsible for the metabolism of S-warfarin. Numerous variant alleles of CYP2C9 have been identified. The CYP2C9*12 (rs9332239) allele harbors a P489S substitution in CYP2C9 which has been shown to result in a 40% decline in catalytic activity in vitro. CASES: Four Caucasian patients with a low mean weekly warfarin dose (MWWD) were genotyped for CYP2C9, VKORC1 and APOE variant alleles. None of the four patients carried the common CYP2C9 variant alleles (*2, *3, *5, *6, *7, *8, *9, *11, *13) despite a relatively low MWWD (23.4±7.94 mg) compared to 208 patients carrying the CYP29C9*1 genotype (32.2±12.65 mg). Given that CYP2C9*12 confers decreased in vitro activity to the enzyme, we investigated whether these patients carried this allele. All four patients were CYP2C9*12 CT heterozygotes. Individual comparisons with patients possessing the same VKORC1 and APOE genotypes also demonstrated lower dose requirements in the patients that possessed CYP2C9*12 allele. CONCLUSIONS: There are no reports of the clinical impact of rs9332239 on CYP2C9 substrates. This is the first report of patients with the rare CYP2C9*12 genotype and lower warfarin dose requirements.