The Comprehensive Post-Acute Stroke Services (COMPASS) study: design and methods for a cluster-randomized pragmatic trial

Background: Patients discharged home after stroke face significant challenges managing residual neurological deficits, secondary prevention, and pre-existing chronic conditions. Post-discharge care is often fragmented leading to increased healthcare costs, readmissions, and sub-optimal utilization of rehabilitation and community services. The COMprehensive Post-Acute Stroke Services (COMPASS) Study is an ongoing cluster-randomized pragmatic trial to assess the effectiveness of a comprehensive, evidence-based, post-acute care model on patient-centered outcomes. Methods: Forty-one hospitals in North Carolina were randomized (as 40 units) to either implement the COMPASS care model or continue their usual care. The recruitment goal is 6000 patients (3000 per arm). Hospital staff ascertain and enroll patients discharged home with a clinical diagnosis of stroke or transient ischemic attack. Patients discharged from intervention hospitals receive 2-day telephone follow-up; a comprehensive clinic visit within 2 weeks that includes a neurological evaluation, assessments of social and functional determinants of health, and an individualized COMPASS Care PlanTM integrated with a community-specific resource database; and additional follow-up calls at 30 and 60 days post-stroke discharge. This model is consistent with the Centers for Medicare and Medicaid Services transitional care management services provided by physicians or advanced practice providers with support from a nurse to conduct patient assessments and coordinate follow-up services. Patients discharged from usual care hospitals represent the control group and receive the standard of care in place at that hospital. Patient-centered outcomes are collected from telephone surveys administered at 90 days. The primary endpoint is patient-reported functional status as measured by the Stroke Impact Scale 16. Secondary outcomes are: caregiver strain, all-cause readmissions, mortality, healthcare utilization, and medication adherence. The study engages patients, caregivers, and other stakeholders (including policymakers, advocacy groups, payers, and local community coalitions) to advise and support the design, implementation, and sustainability of the COMPASS care model. Discussion: Given the high societal and economic burden of stroke, identifying a care model to improve recovery, independence, and quality of life is critical for stroke survivors and their caregivers. The pragmatic trial design provides a real-world assessment of the COMPASS care model effectiveness and will facilitate rapid implementation into clinical practice if successful

NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap4A) and Down-Regulates Immune Response and Cancer Promotion Genes.

Regulation of gene expression is one of several roles proposed for the stress-induced nucleotide diadenosine tetraphosphate (Ap4A). We have examined this directly by a comparative RNA-Seq analysis of KBM-7 chronic myelogenous leukemia cells and KBM-7 cells in which the NUDT2 Ap4A hydrolase gene had been disrupted (NuKO cells), causing a 175-fold increase in intracellular Ap4A. 6,288 differentially expressed genes were identified with P < 0.05. Of these, 980 were up-regulated and 705 down-regulated in NuKO cells with a fold-change ≥ 2. Ingenuity® Pathway Analysis (IPA®) was used to assign these genes to known canonical pathways and functional networks. Pathways associated with interferon responses, pattern recognition receptors and inflammation scored highly in the down-regulated set of genes while functions associated with MHC class II antigens were prominent among the up-regulated genes, which otherwise showed little organization into major functional gene sets. Tryptophan catabolism was also strongly down-regulated as were numerous genes known to be involved in tumor promotion in other systems, with roles in the epithelial-mesenchymal transition, proliferation, invasion and metastasis. Conversely, some pro-apoptotic genes were up-regulated. Major upstream factors predicted by IPA® for gene down-regulation included NFκB, STAT1/2, IRF3/4 and SP1 but no major factors controlling gene up-regulation were identified. Potential mechanisms for gene regulation mediated by Ap4A and/or NUDT2 disruption include binding of Ap4A to the HINT1 co-repressor, autocrine activation of purinoceptors by Ap4A, chromatin remodeling, effects of NUDT2 loss on transcript stability, and inhibition of ATP-dependent regulatory factors such as protein kinases by Ap4A. Existing evidence favors the last of these as the most probable mechanism. Regardless, our results suggest that the NUDT2 protein could be a novel cancer chemotherapeutic target, with its inhibition potentially exerting strong anti-tumor effects via multiple pathways involving metastasis, invasion, immunosuppression and apoptosis

The Rivermead Assessment of Somatosensory Performance (RASP): standardization and reliability data

Objective: To develop a standardized, clinically relevant, quantitative assessment of somatosensory performance in patients with stroke. Design: Prospective observational study and test evaluation. Setting: Local Oxford hospitals and a regional neurological rehabilitation centre. Subjects: Stroke patients with a ”rst, lateralized acute stroke in hospital, and age-matched control subjects. Method: Each patient was assessed in a structured way using a new battery of formal tests of somatosensory performance. Results: A total of 100 patients and 50 controls were fully investigated. Control subjects performed at or near ceiling on all tests, but patients showed impaired performance on all tests. The Rivermead Assessment of Somatosensory Performance (RASP) showed good intra-rater and inter-rater reliability for all subtests. There were however only weak relationships between scores of sensory impairment and scores of motor impairment or mobility and dependence. Conclusions: The RASP provides a practical and reliable assessment of sensory loss, which provides the clinician with a comprehensive picture of the patient’s performance and can be used to inform and monitor rehabilitation and recovery

Ommaya Reservoir Insertion: A Technical Note.

Ommaya reservoir insertion is an elective neurosurgical procedure to deliver repeated intraventricular therapy, but placement can be complicated by malposition of the catheter, clogging, infection or poor postoperative cosmesis. Here, we describe the technique used by the senior author for accurate placement including preassembly of the reservoir and catheter, and recessing of the reservoir so that others may consider the technique for their practice. Results in a consecutive series of 27 Ommaya placements were reviewed. Catheter tip placement accuracy, complications and surgical times were reported. Indications were leptomeningeal cancer or infection. Postoperative imaging showed the catheter tip was located in the frontal horn (96%) or body (4%) of the ipsilateral lateral ventricle. The median surgical time was 36 minutes (range 17-63 minutes). There were no parenchymal or subarachnoid hemorrhages. Infections occurred in 7% (n=2) of cases, and both infections presented greater than 60 days postoperative. In conclusion, we have found that image guidance can optimize accuracy in placement, that preassembly of the reservoir and catheter may be used with a 25-gauge spinal needle stylet to minimize risk of clogging during placement, and that recessing of the reservoir produces the best aesthetic result

Postoperative Propionibacterium endophthalmitis. Treatment strategies and long-term results

Postoperative Propionibacterium endophthalmitis is a condition characterized by exacerbations and remissions that has often been accompanied by recurrence after treatment. The purpose of this study is to evaluate the efficacy of initial therapies in preventing recurrent endophthalmitis and to assess the safety of intraocular lens (IOL) exchange performed during treatment of active endophthalmitis. The records of 22 patients with culture-proven Propionibacterium endophthalmitis treated at one facility were retrospectively reviewed. Two patients presented acutely, were treated with intraocular antibiotic injection alone, and experienced no recurrent inflammation. Twenty patients presented with chronic, delayed-onset pseudophakic endophthalmitis. Eight of these were treated initially with intraocular antibiotic injection alone, and recurrent endophthalmitis developed in seven. Twelve patients with chronic endophthalmitis were initially managed surgically with either pars plana vitrectomy or IOL exchange. Four of the 12 experienced recurrent endophthalmitis. Patients undergoing capsulectomy as part of initial management experienced the lowest rate of recurrent endophthalmitis. Eight patients eventually underwent total capsulectomy and IOL explantation, seven of whom had IOL exchange. None of these eight patients had recurrent endophthalmitis. In seven of the eight, persistent bacterial colonization of the lens capsular remnants was demonstrated. These data suggest that recurrent Propionibacterium endophthalmitis is due to persistence of viable organisms sequestered within lens capsular remnants, and that initial therapy directed toward surgical removal of these sequestered organisms results in a reduced frequency of recurrent endophthalmitis. Intraocular lens exchange with complete capsular removal during active endophthalmitis was not associated with recurrent or persistent endophthalmitis

A Case of Bell's Palsy with an Incidental Finding of a Cerebellopontine Angle Lipoma.

This case report illustrates the potential fallacy of attributing a patient's symptoms to an incidental finding. Serial imaging of small, asymptomatic cerebellopontine angle (CPA) lipomas is favored. It is imperative to accurately diagnose CPA lipoma on imaging and differentiate it from more common CPA lesions. We herein present a patient with symptoms consistent with Bell's palsy and an incidental finding of a CPA lipoma. Additionally, we performed a review of the literature for case reports of patients presenting with facial symptoms and diagnosed with a CPA lipoma