Multicenter prospective cohort study of the Strata valve for the management of hydrocephalus in pediatric patients

Journal ArticleObject. Previous reports suggest that adjustable valves may improve the survival of cerebrospinal fluid shunts or relieve shunt-related symptoms. To evaluate these claims, the authors conducted a prospective multicenter cohort study of children who underwent placement of Strata valves. Methods. Patients undergoing initial shunt placement (Group 1) or shunt revision (Group 2) were treated using Strata valve shunt systems. Valves were adjustable to five performance level settings by using an externally applied magnet. The performance levels were checked using an externally applied hand tool and radiography. Patients were followed for 1 year or until they underwent shunt revision surgery. Between March 2000 and February 2002, 315 patients were enrolled in the study. In Group 1 (201 patients) the common causes of hydrocephalus were myelomeningocele (16%), aqueductal stenosis (14%), and hemorrhage (14%). The overall 1-year shunt survival was 67%. Causes of shunt failure were obstruction (17%), overdrainage (1.5%), loculated ventricles (2%), and infection (10.6%). Patients in Group 2 (114 patients) were older and the causes of hydrocephalus were similar. Among patients in Group 2 the 1-year shunt survival was 71%. There were 256 valve adjustments. Symptoms completely resolved (26%) or improved (37%) after 63% of adjustments. When symptoms improved or resolved, they did so within 24 hours in 89% of adjustments. Hand-tool and radiographic readings of valve settings were the same in 234 (98%) of 238 assessments. Conclusions. The 1-year shunt survival for the Strata valve shunt system when used in initial shunt insertion procedures or shunt revisions was similar to those demonstrated for other valves. Symptom relief or improvement following adjustment was observed in 63% of patients. Hand-tool assessment of performance level settings reliably predicted radiographic assessments

Juvenile pilocytic astrocytoma of the brainstem in children

Journal ArticleObject. In reports involving the operative treatment of brainstem tumors, multiple histological types are often grouped together. To determine prognosis after resection, histology-specific data may be helpful. Methods. Twenty-eight patients with juvenile pilocytic astrocytoma (JPA) of the brainstem (six in the midbrain, four in the pons, and 18 in the medulla) were identified from the medical records. Initial treatment was resection in 25 and biopsy sampling in three. Postoperative imaging revealed gross-total resection (GTR) or resection with linear enhancement (RLE) in 12 of 25 patients and solid residual tumor in the other 13. In 10 of the 13 patients harboring solid residual tumor, observation was undertaken; the residual lesion disappeared in one, was stable in four, and progressed in five. Of the 12 patients with complete excision or RLE only, seven underwent no further treatment, with tumor progression occurring in one. All patients were alive at last follow-up examination (range 0.3-20.4 years, mean 6 years). New neurological deficits commonly appeared immediately after resection but often resolved. In six of the 28 patients, the new postoperative deficit was still present at last follow-up visit. The 5- and 10-year progression-free survival was 74 and 62%, respectively, after GTR or RLE and 19 and 19%, respectively, when solid residual tumor was present. Conclusions. Long-term survival after resection of JPAs of the brainstem has been observed and appears to be related to the extent of initial excision

Hemispherectomy and diaschisis: Rapid improvement in cerebral functions after right hemispherectomy in a six year old child

Neuroradiological, neurological, and neuropsychological studies before and after hemispherectomy for seizures of a six year old boy with left hemiplegia at birth revealed striking postoperative improvement. Seizures ceased and have not recurred. Preoperative EEC studies from seven months of age revealed increasing pathological involvement of the left as well as right hemisphere. Postoperatively, normal tracings over the left hemisphere documented marked and continuing improvement. In contrast to markedly subnormal preoperative WISC-R IQs, retest at 19 months postoperatively showed WISC-R IQs within the normal range, with similar improvement in other tests of cognitive, motor and sensory functions. The arrest and reversal of the preoperative pattern of increasing deterioration and disappearance of pathological involvement of left as well as right hemisphere functions following surgery is consistent with the disappearance of diaschisis as described by von Monakow in 1914, and has conceivably significant clinical as well as theoretical implications.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27432/1/0000470.pd

Development of a poststroke checklist to standardize follow-up care for stroke survivors

Background: Long-termcare for stroke survivors is fragmented and lacks an evidence-based, easy-to-use tool to identify persistent long-term problems among stroke survivors and streamline referral for treatment. We sought to develop a poststroke checklist (PSC) to help health care professionals identify poststroke problems amenable to treatment and subsequent referral. Methods: An instrument development team, supported by measurement experts, international stroke experts, and poststroke care stakeholders, was created to develop a long-term PSC. A list of long-term poststroke problem areas was generated by an international, multidisciplinary group of stroke experts, the Global Stroke Community Advisory Panel. Using Delphi methods, a consensus was reached on which problem areas on the list were most important and relevant to include in a PSC. The instrument development team concurrently created the actual checklist, which provided example language about how to ask about poststroke problem areas and linked patient responses to a specific referral process. Results: Eleven long-term poststroke problem areas were rated highly and consistently among stroke experts participating in the Delphi process (n = 12): secondary prevention, activities of daily living, mobility, spasticity, pain, incontinence, communication, mood, cognition, life after stroke, and relationship with caregiver. These problem areas were included in the long-term PSC. Conclusions: The PSC was developed to be a brief and easy-to-use tool, intended to facilitate a standardized approach for health care providers to identify long-term problems in stroke survivors and to facilitate appropriate referrals for treatment

An occupational therapy intervention for residents with stroke related disabilities in UK care homes (OTCH): cluster randomised controlled trial

Objective To evaluate the clinical efficacy of an established programme of occupational therapy in maintaining functional activity and reducing further health risks from inactivity in care home residents living with stroke sequelae. Design Pragmatic, parallel group, cluster randomised controlled trial. Setting 228 care homes (>10 beds each), both with and without the provision of nursing care, local to 11 trial administrative centres across the United Kingdom. Participants 1042 care home residents with a history of stroke or transient ischaemic attack, including those with language and cognitive impairments, not receiving end of life care. 114 homes (n=568 residents, 64% from homes providing nursing care) were allocated to the intervention arm and 114 homes (n=474 residents, 65% from homes providing nursing care) to standard care (control arm). Participating care homes were randomised between May 2010 and March 2012. Intervention Targeted three month programme of occupational therapy, delivered by qualified occupational therapists and assistants, involving patient centred goal setting, education of care home staff, and adaptations to the environment. Main outcome measures Primary outcome at the participant level: scores on the Barthel index of activities of daily living at three months post-randomisation. Secondary outcome measures at the participant level: Barthel index scores at six and 12 months post-randomisation, and scores on the Rivermead mobility index, geriatric depression scale-15, and EuroQol EQ-5D-3L questionnaire, at all time points. Results 64% of the participants were women and 93% were white, with a mean age of 82.9 years. Baseline characteristics were similar between groups for all measures, personal characteristics, and diagnostic tests. Overall, 2538 occupational therapy visits were made to 498 participants in the intervention arm (mean 5.1 visits per participant). No adverse events attributable to the intervention were recorded. 162 (11%) died before the primary outcome time point, and 313 (30%) died over the 12 months of the trial. The primary outcome measure did not differ significantly between the treatment arms. The adjusted mean difference in Barthel index score at three months was 0.19 points higher in the intervention arm (95% confidence interval −0.33 to 0.70, P=0.48). Secondary outcome measures also showed no significant differences at all time points. Conclusions This large phase III study provided no evidence of benefit for the provision of a routine occupational therapy service, including staff training, for care home residents living with stroke related disabilities. The established three month individualised course of occupational therapy targeting stroke related disabilities did not have an impact on measures of functional activity, mobility, mood, or health related quality of life, at all observational time points. Providing and targeting ameliorative care in this clinically complex population requires alternative strategies

The pro-apoptotic K-Ras 4A proto-oncoprotein does not affect tumorigenesis in the ApcMin/+ mouse small intestine.

BACKGROUND: Alterations in gene splicing occur in human sporadic colorectal cancer (CRC) and may contribute to tumour progression. The K-ras proto-oncogene encodes two splice variants, K-ras 4A and 4B, and K-ras activating mutations which jointly affect both isoforms are prevalent in CRC. Past studies have established that splicing of both the K-ras oncogene and proto-oncogene is altered in CRC in favour of K-ras 4B. The present study addressed whether the K-Ras 4A proto-oncoprotein can suppress tumour development in the absence of its oncogenic allele, utilising the ApcMin/+ (Min) mouse that spontaneously develops intestinal tumours that do not harbour K-ras activating mutations, and the K-rastmDelta4A/tmDelta4A mouse that can express the K-ras 4B splice variant only. By this means tumorigenesis in the small intestine was compared between ApcMin/+, K-ras+/+ and ApcMin/+, K-rastmDelta4A/tmDelta4A mice that can, and cannot, express the K-ras 4A proto-oncoprotein respectively. METHODS: The relative levels of expression of the K-ras splice variants in normal small intestine and small intestinal tumours were quantified by real-time RT-qPCR analysis. Inbred (C57BL/6) ApcMin/+, K-ras+/+ and ApcMin/+, K-rastmDelta4A/tmDelta4A mice were generated and the genotypes confirmed by PCR analysis. Survival of stocks was compared by the Mantel-Haenszel test, and tumour number and area compared by Student's t-test in outwardly healthy mice at approximately 106 and 152 days of age. DNA sequencing of codons 12, 13 and 61 was performed to confirm the intestinal tumours did not harbour a K-ras activating mutation. RESULTS: The K-ras 4A transcript accounted for about 50% of K-ras expressed in the small intestine of both wild-type and Min mice. Tumours in the small intestine of Min mice showed increased levels of K-ras 4B transcript expression, but no appreciable change in K-ras 4A transcript levels. No K-ras activating mutations were detected in 27 intestinal tumours derived from Min and compound mutant Min mice. K-Ras 4A deficiency did not affect mouse survival, or tumour number, size or histopathology. CONCLUSION: The K-Ras 4A proto-oncoprotein does not exhibit tumour suppressor activity in the small intestine, even though the K-ras 4A/4B ratio is reduced in adenomas lacking K-ras activating mutations.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

The DRESS trial: a feasibility randomized controlled trial of a neuropsychological approach to dressing therapy for stroke inpatients

Objective: To investigate two approaches to treating patients with persistent dressing problems and cognitive difficulties following stroke. Design: Pilot randomized controlled trial. Setting: Inpatient stroke rehabilitation service. Subjects: Seventy consecutive stroke patients with persistent dressing problems and accompanying cognitive difficulties at two weeks after their stroke. Interventions: Patients were randomly allocated to six weeks of either a systematic neuropsychological approach, based on analysis of dressing problems and further cognitive testing, or to the control group who received conventional (functional) dressing practice. Both groups received treatment three times a week in accordance with two separately prepared manuals. Main measures: Nottingham Stroke Dressing Assessment (NSDA), Line Cancellation, 10-hole peg transfer test, Object Decision, Gesture Imitation. Patients were assessed at six weeks after randomization by an independent assessor masked to group allocation. Results: Both neuropsychological and functional groups improved performance on the NSDA over the treatment period (31% and 22%, respectively) but there was no significant difference between groups at six weeks. However, the neuropsychological group showed a significantly greater improvement on a line cancellation test of visual neglect (t(62) = 2.1, P < 0.05) and a planned subanalysis for those with right hemisphere damage showed a trend towards better dressing outcome (P = 0.07, one-tailed). Conclusions: Results demonstrate the potential benefits of a systematic neuropsychological approach to dressing therapy, particularly for patients with right hemisphere damage. This study suggests the need for a phase III study evaluating the efficacy of a systematic neuropsychological approach in treating dressing difficulties, targeting patients with right hemisphere stroke and visuospatial impairments

LIGHTSITE II Randomized Multicenter Trial: Evaluation of Multiwavelength Photobiomodulation in Non-exudative Age-Related Macular Degeneration.

INTRODUCTION Photobiomodulation (PBM) represents a potential treatment for non-exudative age-related macular degeneration (AMD). PBM uses wavelengths of light to target components of the mitochondrial respiratory chain to improve cellular bioenergetic outputs. The aim of this study was to further investigate the effects of PBM on clinical, quality of life (QoL) and anatomical outcomes in subjects with intermediate stage non-exudative AMD. METHODS The multicenter LIGHTSITE II study was a randomized clinical trial evaluating safety and efficacy of PBM in intermediate non-exudative AMD. The LumiThera Valeda® Light Delivery System delivered multiwavelength PBM (590, 660 and 850 nm) or sham treatment 3 × per week over 3-4 weeks (9 treatments per series) with repeated treatments at baseline (BL), 4 and 8 months. Subjects were enrolled with 20/32 to 20/100 best-corrected visual acuity (BCVA) and no central geographic atrophy (GA) within the central fovea (500 μm). RESULTS LIGHTSITE II enrolled 44 non-exudative AMD subjects (53 eyes). PBM-treated eyes showed statistically significant improvement in BCVA at 9 months (n = 32 eyes, p = 0.02) with a 4-letter gain in the PBM-treated group versus a 0.5-letter gain in the sham-treated group (ns, p < 0.1) for patients that received all 27 PBM treatments (n = 29 eyes). Approximately 35.3% of PBM-treated eyes showed ≥ 5-letter improvement at 9 months. Macular drusen volume was not increased over time in the PBM-treated group but did show increases in the sham-treated group. While PBM and sham groups both showed GA lesion growth in the trial period, there was 20% less growth in the PBM group over 10 months, suggesting potential disease-modifying effects. No safety concerns or signs of phototoxicity were observed. CONCLUSION These results confirm previous clinical testing of multiwavelength PBM and support treatment with Valeda as a novel therapy with a unique mechanism of action as a potential treatment for non-exudative AMD. TRIAL REGISTRATION Clinicaltrial.Gov Registration Identifier: NCT03878420

A cluster randomised controlled trial of an occupational therapy intervention for residents with stroke living in UK care homes (OTCH): study protocol.

BACKGROUND: The occupational therapy (OT) in care homes study (OTCH) aims to investigate the effect of a targeted course of individual OT (with task training, provision of adaptive equipment, minor environmental adaptations and staff education) for stroke survivors living in care homes, compared to usual care. METHODS/DESIGN: A cluster randomised controlled trial of United Kingdom (UK) care homes (n = 90) with residents (n = 900) who have suffered a stroke or transient ischaemic attack (TIA), and who are not receiving end-of-life care. Homes will be stratified by centre and by type of care provided and randomised (50:50) using computer generated blocked randomisation within strata to receive either the OT intervention (3 months intervention from an occupational therapist) or control (usual care). Staff training on facilitating independence and mobility and the use of adaptive equipment, will be delivered to every home, with control homes receiving this after the 12 month follow-up.Allocation will be concealed from the independent assessors, but the treating therapists, and residents will not be masked to the intervention. Measurements are taken at baseline prior to randomisation and at 3, 6 and 12 months post randomisation. The primary outcome measure is independence in self-care activities of daily living (Barthel Activities of Daily Living Index). Secondary outcome measures are mobility (Rivermead Mobility Index), mood (Geriatric Depression Scale), preference based quality of life measured from EQ-5D and costs associated with each intervention group. Quality adjusted life years (QALYs) will be derived based on the EQ-5D scores. Cost effectiveness analysis will be estimated and measured by incremental cost effectiveness ratio. Adverse events will be recorded. DISCUSSION: This study will be the largest cluster randomised controlled trial of OT in care homes to date and will clarify the currently inconclusive literature on the efficacy of OT for stroke and TIA survivors residing in care homes. TRIAL REGISTRATION: ISRCTN00757750.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Family-led rehabilitation after stroke in India: a randomised controlled trial

Background: Most people with stroke in India have no access to organised rehabilitation services. The effectiveness of training family members to provide stroke rehabilitation is uncertain. Our primary objective was to determine whether family-led stroke rehabilitation, initiated in hospital and continued at home, would be superior to usual care, in a low resource setting. Methods: The Family-led Rehabilitation after Stroke in India (ATTEND) trial was a prospectively randomised open trial with blinded endpoints (PROBE) conducted across 14 hospitals in India. Patients (and their caregivers) were randomised to intervention or usual care by site Coordinators, using a secure web-based system, with minimisation by site and stroke severity. The intervention group received additional structured rehabilitation training, commenced in hospital and continued at home for up to 2 months. The primary outcome was death or dependency, defined by scores 3 to 6 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) as assessed by blinded observers at six months. Secondary outcomes included any serious adverse event, hospital length of stay, activities of daily living, health-related quality of life, anxiety and depression, and caregiver strain. All analyses were intention to treat. Registration: Clinical Trials Registry-India (CTRI/2013/04/003557); Australian New Zealand Clinical Trials Registry (ACTRN12613000078752); and Universal Trial Number (U1111-1138-6707) Findings: A total of 1,250 patients were randomised (623 intervention and 627 control) between 13 January 2014 and 12 February 2016. At six months, 285 of 607 (47·0%) participants in the intervention group were dead or dependent compared to 287 of 605 (47·4%) in the control group (odds ratio 0·98; 95% confidence Interval 0·78 to 1·23, P = 0·87). No significant differences were observed in any of the secondary or safety outcomes. Interpretation: Family-led rehabilitation did not reduce death or dependency after stroke