Therapeutic targeting of ependymoma as informed by oncogenic enhancer profiling.

Genomic sequencing has driven precision-based oncology therapy; however, the genetic drivers of many malignancies remain unknown or non-targetable, so alternative approaches to the identification of therapeutic leads are necessary. Ependymomas are chemotherapy-resistant brain tumours, which, despite genomic sequencing, lack effective molecular targets. Intracranial ependymomas are segregated on the basis of anatomical location (supratentorial region or posterior fossa) and further divided into distinct molecular subgroups that reflect differences in the age of onset, gender predominance and response to therapy. The most common and aggressive subgroup, posterior fossa ependymoma group A (PF-EPN-A), occurs in young children and appears to lack recurrent somatic mutations. Conversely, posterior fossa ependymoma group B (PF-EPN-B) tumours display frequent large-scale copy number gains and losses but have favourable clinical outcomes. More than 70% of supratentorial ependymomas are defined by highly recurrent gene fusions in the NF-κB subunit gene RELA (ST-EPN-RELA), and a smaller number involve fusion of the gene encoding the transcriptional activator YAP1 (ST-EPN-YAP1). Subependymomas, a distinct histologic variant, can also be found within the supratetorial and posterior fossa compartments, and account for the majority of tumours in the molecular subgroups ST-EPN-SE and PF-EPN-SE. Here we describe mapping of active chromatin landscapes in 42 primary ependymomas in two non-overlapping primary ependymoma cohorts, with the goal of identifying essential super-enhancer-associated genes on which tumour cells depend. Enhancer regions revealed putative oncogenes, molecular targets and pathways; inhibition of these targets with small molecule inhibitors or short hairpin RNA diminished the proliferation of patient-derived neurospheres and increased survival in mouse models of ependymomas. Through profiling of transcriptional enhancers, our study provides a framework for target and drug discovery in other cancers that lack known genetic drivers and are therefore difficult to treat.

Return to sports following discectomy: does a consensus exist?

INTRODUCTION: In the USA, lumbar discectomy is one of the most commonly performed spinal procedures. As certain sports are considered to be major risk factors for disc herniation, the question remains as to when highly active patients should return to their previous level of activity. This study aimed to analyze spine surgeons' opinions on when patients may return to activities following discectomy as well as their underlying rationale for their decision. METHODS: A questionnaire was designed by five different fellowship-trained spine surgeons for the 168 members of the Spine Society of Australia. Questions on the surgeons experience, decision making, preferred surgical technique, the postoperative rehabilitation and the response to patient expectations were included. RESULTS: In total, 83.9% of surgeons discuss the postoperative level of activity with their patients. Sport is considered as an important contributor for good functional outcome by 71.0% of surgeons. Surgeons recommend avoiding, often permanently, weightlifting (35.7%) of the time, rugby (21.4%), horseback riding (17.9%) as well as martial arts (14.3%) postoperatively even with previous training. The return to high levels of activity is considered as a major risk factor for disc herniation recurrence by 25.8% of surgeons. Return to high level of activity is typically recommended after 3 months by 48.4% of surgeons. CONCLUSION: So far no consensus on the rehabilitation protocol and return to level of activity exists. Recommendations depend on personal experience as well as the individuals' training, and typically, a period of avoidance of sport for up to 3 months is recommended. LEVEL OF EVIDENCE: Level III, therapeutic and prognostic study.

Safety, satisfaction and cost savings of accelerated infusions of standard and intensified-dose infliximab for inflammatory bowel disease.

BACKGROUND: Infliximab remains a mainstay for the treatment of inflammatory bowel disease (IBD), but a long infusion duration and subsequent monitoring can be burdensome to patients and healthcare providers. AIMS: To assess the safety of accelerated infusions for standard and dose-intensified infliximab regimens, and the effect on patient satisfaction and potential cost savings. METHODS: Patients with IBD on a stable maintenance dose of infliximab and in clinical remission received one or more accelerated infusions: over 30 min if receiving a standard dose (5 mg/kg), or over 60 min if receiving dose-intensified infliximab (up to 10 mg/kg). Outcomes included incidence of reactions (acute or delayed), patient satisfaction and potential cost savings. We also explored infliximab trough levels after one and three accelerated infusions. RESULTS: Fifty-two patients who received 150 infusions were studied. Incidence of reactions to accelerated infusions was 3.3% (3 out of 89) with a standard dose and 0% (out of 61) with dose-intensified infliximab. Reactions were delayed, mild and self-limiting. None required drug cessation. Patient satisfaction was improved with shortened infusion time as compared with the patients' previous experiences (P = 0.00002). Mean plasma trough level of infliximab reduced from 9.3 mg/L (±4.9) to 7.9 mg/L (±4.1) (P = 0.02) with accelerated infusions, but none developed anti-infliximab antibodies. Nursing cost savings were estimated as $123.52 and $247.04 per patient per year for standard and dose-intensified infliximab respectively. CONCLUSION: Accelerated infliximab infusions for standard and dose-intensified regimens seem to be safe and improved patient satisfaction. Potential impact on drug trough levels requires further investigations.

Can Contrast-Enhanced Spectral Mammography (CESM) Reduce Benign Breast Biopsy?

Objectives: To evaluate the potential of contrast-enhanced spectral mammography (CESM) in reducing benign breast biopsy rate, thereby improving resource utilization. To explore its potential as a value-adding modality in the management of BI-RADS 4/5 lesions. Materials and Methods: This was a prospective study conducted between July 2016 and September 2018. Patients with BI-RADS 4/5 lesions detected on conventional imaging (mammogram, digital breast tomosynthesis, and ultrasound) were enrolled for adjunct CESM. Histopathologic correlation was done for all lesions. Additional suspicious lesions detected on CESM were all identified on second-look ultrasound and subsequently biopsied. Images were evaluated independently by two radiologists trained in breast imaging using BI-RADS classification. Presence of enhancement on CESM, BI-RADS score, and histopathology of each lesion were analyzed and tested with the chi-square/fisher-exact test for statistical significance. Results: The study included 105 lesions in 63 participants-1 man and 62 women, an average age of 53.7 ± 10.8 years. On CESM, 22 (20.9%) of the lesions did not show enhancement. All 22 lesions had been classified as BI-RADS 4A and were subsequently proven to be benign. Of the remaining 83 enhancing lesions, 54 (65.1%) were malignant and 29 (34.9%) were benign (p < 0.05). CESM detected 6 additional lesions which were not identified on initial conventional imaging. Four of these were proven malignant and were in a different quadrant than the primary lesion investigated. Conclusion: There is evidence that the absence of enhancement in CESM strongly favors benignity. It may provide the reporting radiologist with greater confidence in imaging assessment, especially in BI-RADS 4A cases, where a proportion of them are in actuality BI-RADS 3. Greater accuracy of BI-RADS grading can reduce nearly half of benign biopsies and allow better resource allocation. CESM also increases the detection rate of potentially malignant lesions, thereby changing the treatment strategies.

Juvenile muscular atrophy of the distal upper extremity (Hirayama syndrome): a systematic review.

INTRODUCTION: Hirayama syndrome is likely caused by a forward displacement of the posterior dura during cervical flexion leading to changes in the muscles of the fingers and wrist. The aim of this systematic review was to document the number of reported cases, the necessity of dynamic MRI of the cervical spine and the subsequent treatment. METHODS AND MATERIALS: A systematic review was conducted and the Pubmed/Medbase, Cochrane, Google, Embase and Ovid database were searched for (Hirayama) AND ((disease) OR (syndrome)). A total of 42 studies were included for analysis reporting 2311 patients. RESULTS: The mean age was 20.2 ± 2.26 years and predominantly males (92.8%) were identified. On MRI the "snake eyes" appearance of the spinal cord was present in 27.8% and the typical time between onset of symptoms and diagnosis was 41.5 ± 16.4 months. A variety of different treatments have been reported, although there is no substantial evidence that any of them are superior to observation. CONCLUSION: The delay in diagnosis from initial presentation of symptoms shows that this condition may be underdiagnosed in a variety of cases. Further, this study shows the necessity of either a dynamic MRI in flexion or a static MRI scan in neutral position and in flexion, to identify functional spinal and/or foraminal stenosis for a prompt diagnosis and subsequent treatment.

Integration of clinical pharmacists into a heart failure clinic within a safety-net hospital.

BACKGROUND: Management of heart failure with reduced ejection fraction (HFrEF) requires timely initiation and up-titration of guideline-directed medical therapy (GDMT). In safety-net hospitals (SNHs), limited health care staff and resources make achievement of optimal medical therapy challenging. Recent studies have shown that medication titration performed by clinical pharmacists can improve outcomes in ambulatory management of HFrEF; however, the impact of these services within an SNH remains unknown. OBJECTIVE: Determine the impact of integrating clinical pharmacists into a heart failure (HF) clinic on initiation and titration of GDMT within an SNH. METHODS: We performed a single-center retrospective cohort study of patients with HFrEF treated in an ambulatory HF medication titration clinic within an SNH before and after clinical pharmacist integration. Primary outcomes included dose optimization rates of GDMT, time between clinic visits, and time to optimization of GDMT. Exploratory secondary outcomes were all-cause, HF, and cardiovascular acute care service utilization and all-cause, HF, and cardiovascular mortality before and after clinical pharmacist integration up to 6 months after initial clinic visit. RESULTS: A total of 153 patients with HFrEF were treated. Baseline characteristics in the pre- and postintervention groups were comparable. After clinical pharmacist integration, there was a statistically significant improvement in optimization of renin-angiotensin-aldosterone system inhibitor or hydralazine-nitrate equivalent (82% vs. 94%, P = 0.02). Dose optimization rates of beta-blockers (90% vs. 83%, P = 0.22) and mineralocorticoid receptor antagonists (57% vs. 57%, P > 0.99) were unchanged. There was a statistically significant reduction in mean time between clinic visits (26 vs. 14 days, P < 0.001) and in mean time to optimization of GDMT (88 vs. 45 days, P = 0.002). All-cause mortality was reduced (13% vs. 2%, P = 0.01). CONCLUSION: In SNHs, where limited health care staff and resources present as barriers to timely initiation and titration of GDMT, integration of clinical pharmacists into HF clinics can serve as a practical solution.

DNA methylation and breast cancer-associated variants.

BACKGROUND: A breast cancer polygenic risk score (PRS) comprising 313 common variants reliably predicts disease risk. We examined possible relationships between genetic variation, regulation, and expression to clarify the molecular alterations associated with these variants. METHODS: Genome-wide methylomic variation was quantified (MethylationEPIC) in Asian breast cancer patients (1152 buffy coats from peripheral whole blood). DNA methylation (DNAm) quantitative trait loci (mQTL) mapping was performed for 235 of the 313 variants with minor allele frequencies > 5%. Stability of identified mQTLs (p < 5e-8) across lifetime was examined using a public mQTL database. Identified mQTLs were also mapped to expression quantitative trait loci (eQTLs) in the Genotype-Tissue Expression Project and the eQTLGen Consortium. RESULTS: Breast cancer PRS was not associated with DNAm. A higher proportion of significant cis-mQTLs were observed. Of 822 significant cis-mQTLs (179 unique variants) identified in our dataset, 141 (59 unique variants) were significant (p < 5e-8) in a public mQTL database. Eighty-six percent (121/141) of the matched mQTLs were consistent at multiple time points (birth, childhood, adolescence, pregnancy, middle age, post-diagnosis, or treatment). Ninety-three variants associated with DNAm were also cis-eQTLs (35 variants not genome-wide significant). Multiple loci in the breast cancer PRS are associated with DNAm, contributing to the polygenic nature of the disease. These mQTLs are mostly stable over time. CONCLUSIONS: Consistent results from DNAm and expression data may reveal new candidate genes not previously associated with breast cancer.

Cognitive Function and Functional Mobility Predict Exercise Adherence in Older Adults Who Fall.

INTRODUCTION: Strength and balance exercises prevent falls. Yet, exercise adherence is often low. To maximize the benefit of exercise on falls prevention, we aimed to identify baseline cognitive and mobility factors that predict adherence to the Otago Exercise Program (OEP) - a home-based exercise program proven to prevent falls. METHODS: We conducted a secondary longitudinal analysis of data from a randomized clinical trial (RCT) (OEP compared with usual care) among 172 participants who were assigned to the OEP intervention of the RCT. Adherence to the OEP was calculated as a percent score (i.e., [frequency of strength and balance retraining session per week/3 strength and balance retraining sessions per week] × 100). Executive function (i.e., mental flexibility) was measured using the Trail Making Tests (Part A and B: TMT B - TMT A) and the Digit Symbol Substitution Test (DSST). Short-term memory and encoding was measured using the Verbal Digits Forward test. Executive function (i.e., inhibition and working memory) was measured using the Stroop Color-Word Test and the Verbal Digits Forward minus Verbal Digits Backward test. Mobility was assessed using the Short Performance Physical Battery and the Timed Up and Go test. We used general estimation equations analysis to determine the predictors of adherence to the OEP. RESULTS: Better set shifting (ß = -0.06, z = -2.43, [SE = 0.02] p = 0.018] predicted greater OEP adherence. Greater attention and short-term memory (ß = -6.99, z = -2.37 [SE = 2.95]) predicted poorer OEP adherence. Response inhibition, processing speed, working memory, and mobility assessed by the SPPB were not associated with adherence. Poorer baseline Timed Up and Go (ß = 1.48 z = 1.94, [SE = 0.76]; p < 0.001), predicted better OEP adherence. CONCLUSION: Specific cognitive processes (i.e., executive function of set shifting, attention, and short-term memory) and functional mobility predicted exercise adherence. Further research needs to explore the pathways that explain why better attention and short-term memory predicted lower adherence and why poorer functional mobility led to better OEP adherence.

COVID-19: Highlighting Health Disparities in the Los Angeles Latinx Community.

Objective: Characterization of COVID-19 in the Latinx community is necessary for guiding public health initiatives, health system policy, clinical management practices, and improving outcomes. Our aim was to describe the socioeconomic background and clinical profile of patients with COVID-19 at a large public hospital in Los Angeles to improve health disparities leading to poor outcomes during the pandemic.Design, Setting and Participants: A single center retrospective cross-sectional study of all patients with a positive polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who presented to Los Angeles County (LAC)+University of Southern California (USC) Medical Center between March 15, 2020 and April 30, 2020.Methods: We describe patient characteristics, socioeconomic factors, laboratory findings, and outcomes of the first 278 patients to present to LAC+USC Medical Center with COVID-19.Results: Patients self-identified as Hispanic (82.4%) or non-Hispanic (17.6%). Hispanic patients presented later from symptom onset (6 days vs 3 days, P = 0.027) and had higher post-intubation mortality (40.9% vs. 33.3%, P = 1), intensive care unit (ICU) mortality (31.1% vs. 22.2%, P = 0.87), and overall mortality (11.1% vs 10.2%, P = 1). However, the difference in admission rates, mechanical ventilation rates, and overall mortality rates were not statistically significant. A majority of patients, 275/278 (98.9%), reported residency ZIP codes in areas of higher population density, higher percentage of Latinx, born outside the United States, lower median income, and lower high school graduation rate when compared to the rest of Los Angeles County. Regression analysis within the Hispanic cohort found that age, history of hypertension, history of diabetes, lactate dehydrogenase (LDH), and C-reactive protein (CRP) were predictors of mechanical ventilation and mortality.Conclusion: We show the Latinx community has been disproportionally affected by the pandemic in Los Angeles and we identified multiple socioeconomic and clinical characteristics that predispose this population to COVID-19 infection. This study highlights the need for change in local and national strategies to protect vulnerable communities during public health outbreaks.

Bilateral sequential lung transplantation in Jehovah's Witnesses.

The ethical concerns of refusing lifesaving treatments after receiving an already limited resource such as a solid organ transplantation in a Jehovah's Witness patient have been discussed in the literature. Many of these studies have concluded that with a multidisciplinary approach, solid organ transplantation is possible in the setting of Jehovah's Witness patients. To date, there are no reported cases of bilateral sequential lung transplantation in the literature. We report two successful cases of bilateral sequential lung transplantation in Jehovah's Witness patients with excellent long-term follow-up.

Transition of femoral-jugular to dual-stage left subclavian without discontinuation of extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is a technology that has allowed further cardiopulmonary support in the setting of respiratory failure refractory to mechanical ventilation. While it has evolved since its first description, one area of improvement continues to be its implementation. With advancements in cannulation techniques, in recent years, there has been a plethora of new cannulas that has been introduced in the market. For urgent venous-venous cannulation, the right internal jugular vein along with either femoral veins remain the most utilized strategy due to minimal need for imaging support. This allows for safe bedside cannulation. However, as the number of days of ECMO support continue to increase, transitioning to a cannulation strategy that is easier to ambulate with and more comfortable is preferred. Therefore, we describe a method for transitioning from right jugular-femoral cannulation to left subclavian placement of the Crescent Dual-Lumen catheter without interrupting ECMO support.

Concomitant surgical aortic valve replacement with bilateral orthotopic lung transplantation.

Concomitant cardiac surgery at the time of lung transplantation while uncommon has been shown to have acceptable morbidity and mortality. We present a case of a 66-year-old man with a history of interstitial pulmonary fibrosis with end-stage lung disease who presented with moderate aortic stenosis and severe aortic regurgitation. He underwent a bioprosthetic surgical aortic valve replacement at the time of bilateral orthotopic lung transplant and recovered without any major complications.

Contemporary outcomes of coronary artery bypass grafting in obese patients.

BACKGROUND: This study evaluated the impact of obesity on outcomes of coronary artery bypass grafting (CABG) with particular attention to cases using bilateral internal mammary arteries (BIMAs). METHODS: Patients undergoing isolated CABG from 2011 to 2017 at a single institution were categorized by body mass index (BMI): 18.5 to 24.9 kg/m2 , 25.0 to 29.9 kg/m2 , 30.0 to 34.9 kg/m2 , and ≥35 kg/m2 , respectively. The primary outcomes were mortality and readmission. Subgroup analysis was performed on CABGs using BIMAs. Adjusted Cox model curves were used for survival analyses and cumulative incidence function for readmissions. RESULTS: A total of 4980 patients underwent CABG with BMIs of 18.5 to 24.9 kg/m2 (17.8%; n = 884), 25.0 to 29.9 kg/m2 (35.0%; n = 1745), 30.0 to 34.9 kg/m2 (27.5%; n = 1368), and ≥35 kg/m2 (19.7%; n = 983), respectively. Patients with BMI 18.5 to 24.9 kg/m2 had a higher overall Society of Thoracic Surgeons predicted risk of mortality. Adjusted survival was similar across BMI groups, and readmission risk was highest in those with a BMI of 18.5 to 24.9 kg/m2 (P = .01). Increasing BMI was associated with higher rates of postoperative deep sternal wound infection (DSWI). CABG was performed with BIMA in 820 (16%). In patients undergoing CABG with BIMA use, there were no differences in survival, readmissions, or DSWI rates between BMI groups. CONCLUSIONS: CABG, including with the use of BIMA, can be performed in obese patients without an increased risk of mortality or hospital readmission out to 5 years. Although rates of postoperative DSWI increase with increasing BMI, this finding did not appear to be magnified in patients with BIMA, although the sample size was limited in this subanalysis. These data support the notion that BIMA use should not be precluded in the obese.

Hepatocellular carcinoma incidence post direct-acting antivirals in hepatitis C-related advanced fibrosis/cirrhosis patients in Australia.

BACKGROUND: Despite efficacy in HCV eradication, direct-acting antiviral (DAA) therapy has raised controversies around their impact on hepatocellular carcinoma (HCC) incidence. Herein we reported the first Australian data on HCC incidence in DAA-treated HCV patients with advanced fibrosis/cirrhosis. METHODS: We conducted a retrospective single center study of DAA-treated HCV patients with advanced fibrosis/cirrhosis from April 2015 to December 2017. Patients with prior HCC were included if they had complete response to HCC treatment. RESULTS: Among 138 patients who completed DAA therapy, 133 (96.4%) achieved sustained virologic response (median follow-up 23.8 months). Ten had prior HCC and 5/10 (50.0%) developed recurrence, while de novo HCC developed in 7/128 (5.5%). Median time from DAA to HCC diagnosis was 34 weeks in recurrent HCC vs. de novo 52 weeks (P = 0.159). In patients with prior HCC, those with recurrence (vs. without) had shorter median time between last HCC treatment and DAA (12 vs. 164 weeks, P < 0.001). On bivariate analysis, failed sustained virologic response at 12 weeks (SVR12) (P = 0.011), platelets (P = 0.005), model for end-stage liver disease (MELD) score (P = 0.029), alpha fetoprotein (AFP) (P = 0.013), and prior HCC (P < 0.001) were associated with HCC post-DAA. On multivariate analysis, significant factors were prior HCC (OR = 4.80; 95% CI: 1.47-48.50; P = 0.010), failed SVR12 (OR = 2.83; 95% CI: 1.71-16.30; P = 0.016) and platelets (OR = 0.97; 95% CI: 0.95-0.99; P = 0.009). CONCLUSIONS: Our study demonstrates a high incidence of recurrent HCC in HCV patients with advanced fibrosis/cirrhosis treated with DAA. Factors associated with HCC development post-DAA were more advanced liver disease, failed SVR12 and prior HCC, with higher rates of recurrence in those who started DAA earlier.

Hepatitis C treatment for difficult to access populations: can telementoring (as distinct from telemedicine) help?

BACKGROUND: Although hepatitis C virus (HCV) infection is curable, treatment of difficult to access populations (DTAP) presents unique challenges. Project ECHO (PE) (Extension for Community Healthcare Outcomes) is a telementoring programme adopted to support clinicians treating DTAP. AIMS: To determine if the PE model supports primary care clinicians treating HCV and to compare cohort of PE patients with those in a tertiary liver clinic (TLC). METHODS: Weekly PE group video conferences were conducted. Clinical information, laboratory indices, psychosocial elements and treatment outcomes, including sustained virological response (SVR) data were recorded in the first 100 consecutive cases and retrospectively compared to 100 consecutive patients seen at a TLC from July 2016 to April 2017. RESULTS: Some patient characteristics were similar between PE and TLC: gender (72% vs 75% male; P = 0.23), median age (45 vs 50; P = 0.344) and the proportion of treatment naïve patients (95.0% vs 90.9%). Treatment for HCV was commenced in 78% of the PE patients and 81% of the TLC patients; 67/68 of the TLC patients and 60/61 PE patients with virological follow up who completed treatment and attended follow up have confirmed SVR. PE patients are more likely to have ongoing substance use (44% vs 17% P < 0.001), be active intravenous drug users (32% vs 17%; P < 0.001) and polysubstance abusers (26% vs 7%; P < 0.001) and were more likely to be taking opioid substitution therapy (74% vs 20%; P < 0.001). Indigenous patients were three times more greatly represented in PE (15% vs 5%; P = 0.018). CONCLUSION: PE is an effective model to support primary healthcare providers treating HCV in DTAP with similar rates of treatment uptake and SVR compared to patients in TLC.

Examining the Inter-relations of Depression, Physical Function, and Cognition with Subjective Sleep Parameters among Stroke Survivors: A Cross-sectional Analysis.

GOAL: Stroke survivors commonly experience depression as well as deficits in physical and cognition function. Emerging evidence also suggests sleep quality is compromised poststroke. Our primary objective was to examine the association of subjective sleep parameters (ie, total PSQI score) with depression, health related quality of life, physical function, and cognition among stroke survivors. MATERIALS AND METHODS: Cross-sectional analysis of 72 older adults with chronic stroke (≥6 months postischemic stroke) enrolled in a randomized controlled trial of exercise or cognitive enrichment. Subjective sleep parameters were assessed using the Pittsburgh Sleep Quality Index (PSQI). We report total PSQI score and specific PSQI parameter scores (ie, PSQI-subjective sleep quality, PSQI-sleep latency, PSQI-sleep duration, PSQI-habitual sleep efficiency, PSQI-sleep disturbances, PSQI-use of sleep medication, and PSQI-daytime dysfunction). Bivariate correlations and multivariate linear regression assessed associations between subjective sleep parameters and depression/health related quality of life, physical function, and cognition. FINDINGS: For bivariate correlations, depression was significantly associated with global PSQI, PSQI-subjective sleep quality, PSQI-habitual sleep efficiency, and PSQI-daytime dysfunction. Health related quality of life was significantly associated with PSQI-sleep medication. Physical function and health was significantly associated with PSQI-subjective sleep quality, PSQI-sleep latency, PSQI-sleep duration, and PSQI-daytime dysfunction. Multivariate linear regression demonstrated that PSQI-daytime dysfunction predicted depression and physical function; PSQI-subjective sleep quality predicted depression. No significant associations between global PSQI subjective sleep parameters with cognition were observed. CONCLUSION: Poor subjective sleep parameters and PSQI-subjective sleep quality among stroke survivors were associated with depression; PSQI-daytime dysfunction was associated with physical function. Thus, sleep should be considered in the management of those who have suffered a stroke to optimize poststroke rehabilitation outcomes.

Molecular Classification and Management of Rare Pediatric Embryonal Brain Tumors.

PURPOSE OF REVIEW: Malignant embryonal brain tumors (EBTs) of childhood span a wide clinical spectrum but can share remarkably similar morphologic features. This overlap presents significant diagnostic challenges, particularly for tumor entities that are rarely encountered in clinical practice and for which diagnostic criteria were poorly defined. This review will provide an update on the evolving characterization and treatment of rare EBTs. RECENT FINDINGS: Rapid advances in genomic tools have led to the discovery of robust molecular markers, and identification of novel tumor types and subtypes for almost all major categories of pediatric brain tumors. These developments have had significant impact on improving the diagnostic classification of the rare EBTs, particularly for tumors with newly recognized C19MC alterations, central nervous system primitive neuroectodermal tumors (CNS-PNET), and pineoblastoma (PB). These important developments in the clinical and molecular understanding of rare EBTs are paving the way for novel therapeutic strategies and improved clinical management.

Can we improve cognitive function among adults with osteoarthritis by increasing moderate-to-vigorous physical activity and reducing sedentary behaviour? Secondary analysis of the MONITOR-OA study.

BACKGROUND: Preliminary evidence suggests osteoarthritis is a risk factor for cognitive decline. One potential reason is 87% of adults with osteoarthritis are inactive, and low moderate-to-vigorous physical activity and high sedentary behaviour are each risk factors for cognitive decline. Thus, we investigated whether a community-based intervention to increase moderate-to-vigorous physical activity and reduce sedentary behaviour could improve cognitive function among adults with osteoarthritis. METHODS: This was a secondary analysis of a six month, proof-of-concept randomized controlled trial of a community-based, technology-enabled counselling program to increase moderate-to-vigorous physical activity and reduce sedentary behaviour among adults with knee osteoarthritis. The Immediate Intervention (n = 30) received a Fitbit® Flex™ and four bi-weekly activity counselling sessions; the Delayed Intervention (n = 31) received the same intervention two months later. We assessed episodic memory and working memory using the National Institutes of Health Toolbox Cognition Battery. Between-group differences (Immediate Intervention vs. Delayed Intervention) in cognitive performance were evaluated following the primary intervention (i.e., Baseline - 2 Months) using intention-to-treat. RESULTS: The intervention did not significantly improve cognitive function; however, we estimated small average improvements in episodic memory for the Immediate Intervention vs. Delayed Intervention (estimated mean difference: 1.27; 95% CI [- 9.27, 11.81]; d = 0.10). CONCLUSION: This small study did not show that a short activity promotion intervention improved cognitive health among adults with osteoarthritis. However, the effects of increased moderate-to-vigorous physical activity and reduced sedentary behaviour are likely to be small and thus we recommend subsequent studies use larger sample sizes and measure changes in cognitive function over longer intervals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Protocol Registration System: NCT02315664 ; registered 12 December, 2014; https://clinicaltrials.gov/ct2/show/NCT02315664?cond=NCT02315664&rank=1.

Cross-cultural adaptation and psychometric properties of the Chinese tinnitus functional index.

OBJECTIVES: To establish the reliability, validity and responsiveness of the Chinese version of the Tinnitus Functional Index (TFI-CH) in measuring tinnitus severity in Hong Kong Chinese population. DESIGN: This is a cross-sectional psychometric validation study. STUDY SAMPLE: Subjects were 124 adult Chinese who attended the audiology clinics in a hospital setting for tinnitus treatment. RESULTS: The TFI-CH showed good internal consistency reliability (α = 0.94) and test-retest reliability (ICC = 0.84). Confirmatory factor analysis revealed that the TFI-CH has eight factors which are exactly the same as the original version. The TFI-CH has good convergent and divergent validity as supported by the strong correlation of the overall scale with other tinnitus-related distress measures (r = 0.86, p < 0.01) and weaker correlation with the general health status measures. Moderate to strong effect sizes obtained 3 months after initial visit indicated that the TFI-CH is responsive in detecting change in tinnitus suffering. CONCLUSIONS: The results of this study demonstrate that the TFI-CH is a reliable and valid measure which should be useful in both clinical and research settings for intake assessment and for measuring treatment-related changes in tinnitus.