Setting a patient-centered research agenda for cerebral palsy: a participatory action research initiative.

AIM: To establish a patient-centered research agenda for cerebral palsy (CP). METHOD: We engaged a large cross-section of the extended community of people living with CP and those providing healthcare to people with CP ('the community') in an educational series and collaborative survey platform to establish an initial list of prioritized research ideas. After online workshops, a facilitated Delphi process was used to select the 20 highest priorities. Select participants attended an in-person workshop to provide comment and work toward consensus of research priorities. RESULTS: A research agenda for CP was developed by the community, which included consumers, clinicians, and researchers interested in advancing the established research agenda. The results included the top 16 research concepts produced by the process to shape and steward the research agenda, and an engaged cross-section of the community. INTERPRETATION: It has been shown that proactively engaging consumers with clinical researchers may provide more meaningful research for the community. This study suggests that future research should have more focus on interventions and outcomes across the lifespan with increased emphasis on the following outcome measures: function, quality of life, and participation. WHAT THIS PAPER ADDS: A patient-centered research agenda for cerebral palsy was established. Comparative effectiveness of interventions, physical activity, and understanding ageing were leading themes. Longitudinal studies across the lifespan, clinical spectrum, and ages were highly ranked. Participants reported high value for participation outcomes. Participants reported great appreciation for the engagement between consumers and clinician researchers.

Cerebral palsy research network community registry adult surveys on function & pain: Successes, challenges, and future directions.

NARRATIVE SUMMARY: The formation of a patient-reported outcomes registry to provide information about functional changes and pain among adults with cerebral palsy (CP) was identified as a priority to address the gap in knowledge and practice about aging and CP. The Cerebral Palsy Research Network collaborated with consumers, clinicians, and researchers to create an interactive internet platform, MyCP, to host a Community Registry. MyCP also provides educational programming, access to webinars and community forums, and fitness opportunities. The registry hosts surveys on function and pain for adults with CP, which provide cross-sectional and longitudinal data about these important issues. Surveys include previously validated measures with normative values that have been used with other populations and investigator developed questions. Enrollment in the registry is growing but needs to reflect the population of adults with CP, which limits generalizability. Future initiatives involve strategies to increase consumer engagement and enrollment.

Adults with cerebral palsy and functional decline: A cross-sectional analysis of patient-reported outcomes from a novel North American registry.

BACKGROUND: Adults with cerebral palsy (CP) have unique healthcare needs and risks, including high risk of functional decline. Understanding functional decline is an area of priority for CP research. OBJECTIVE: Describe factors associated with patient-reported changes in function among adults with CP living in the community. METHODS: Cross-sectional analysis of adult patient-reported outcomes collected by the CP Research Network (CPRN) Community Registry. RESULTS: Participants included 263 respondents (76% female (n = 200); mean age 42 years (SD 14); 95% White (n = 249); 92% non-Hispanic (n = 241)). Many reported functional changes, most commonly a decline in gross motor function since childhood (n = 158, 60%). Prevalence of gross motor decline varied significantly by Gross Motor Function Classification System (GMFCS) level (p < 0.001), but neither hand function decline (p = 0.196) nor communication decline (p = 0.994) differed by GMFCS. All types of decline increased with increasing age, with statistically significant differences between age groups (p < 0.001 gross motor; p = 0.003 hand function; p = 0.004 communication). Those with spastic CP (n = 178) most commonly reported gross motor functional decline (n = 108/178, 60.7%). However, the prevalence of gross motor decline did not significantly differ between those with spastic CP and those without spastic CP (p = 0.789). CONCLUSIONS: Many adults in the CPRN Community Registry reported functional decline, most commonly in gross motor function. Functional decline across domains increased with age. Further research into risk stratification and preventive and rehabilitative measures is needed to address functional decline across the lifespan.

A multicenter initiative to reduce intrathecal baclofen pump surgical site infection: a Cerebral Palsy Research Network quality improvement project.

OBJECTIVE: Intrathecal baclofen (ITB) therapy is an effective treatment for spasticity and dystonia in children with cerebral palsy (CP). However, ITB pump surgery is associated with one of the highest rates of surgical site infection (SSI) in medicine, leading to significant morbidity and expense. Surgical protocols have reduced the rate of SSI in children with other CNS implants, and single-center protocols have been effective in ITB surgery in pediatrics. The authors describe the first multicenter quality improvement (QI)-driven standardized protocol for ITB pump surgery in children with CP across the Cerebral Palsy Research Network (CPRN), implemented with the aim of reducing ITB-associated SSI. METHODS: SSI was defined as a culture-positive infection, ITB pump system removal for suspected infection, or wound dehiscence with exposed hardware. Each center reported historical infection rates for at least 3 years before initiating the SSI protocol (preintervention phase). After initiation of a 13-step surgical protocol, a consecutive series of 130 patients undergoing 149 surgical procedures for ITB at four CPRN tertiary pediatric neurosurgery centers were prospectively enrolled at surgery during a 2-year study period (intervention phase). QI methodology was used, including development of a key driver diagram and tracking performance using run and control charts. The primary process measure goal was documented compliance with 80% of the protocol steps, and the primary outcome measure goal was a 20% reduction in 90-day infection rate. Patient characteristics were collected from the CPRN Research Electronic Data Capture registry, including age at surgery, BMI, Gross Motor Function Classification System level, and pattern of spasticity. RESULTS: The aggregated preintervention 90-day ITB SSI rate was 4.9% (223 procedures) between 2014 and 2017. During the intervention phase, 136 of 149 ITB surgeries performed met inclusion criteria for analysis. The mean documented compliance rate with protocol steps was 75%, and the 90-day infection rate was 4.4%, with an average of 42 days from index surgery to infection. CONCLUSIONS: This is the first multicenter QI initiative designed to reduce SSI in ITB surgery in children with CP. Ongoing enrollment and expansion of the protocol to other CPRN centers will facilitate identification of patient- and procedure-specific risk factors for SSI, and iterative plan-do-study-act cycles incorporating these data will further decrease the risk of SSI for ITB surgery in children.

Adults with cerebral palsy and chronic pain experience: A cross-sectional analysis of patient-reported outcomes from a novel North American registry.

BACKGROUND: Chronic pain is common among adults with cerebral palsy (CP) and an area of priority for research and treatment. OBJECTIVE: Describe the pain experience and its functional and quality of life impact among adults with CP with chronic pain in the community. METHODS: Cross-sectional analysis of adult patient-reported outcomes collected by the Cerebral Palsy Research Network Community Registry. RESULTS: Among all participants in the Community Registry, n = 205 reported having chronic pain, and 73 % of those (n = 149) completed the Chronic Pain Survey Bundle (75 % female; mean age 43 years (SD 14 years); 94 % White; 91 % non-Hispanic). Back and weight-bearing joints of lower extremities were most frequently reported as painful. There were no differences in average pain severity scores between varying GMFCS levels (H = 6.25, p = 0.18) and age groups (H = 3.20, p = 0.36). Several nonpharmacologic interventions were most frequently reported as beneficial. Participants with moderate to severe average pain scores (5-10) had higher levels of pain interference (p < 0.01) and depression (p < 0.01), and lower levels of satisfaction with social roles (p < 0.01) and lower extremity function (p < 0.01). Pain interference was significantly positively correlated with depression, and negatively correlated with upper and lower extremity function and satisfaction with social roles. CONCLUSIONS: Chronic pain is experienced by adults with CP of varying ages and functional levels and is associated with several adverse quality of life and functional outcomes. Improved understanding of chronic pain in this population will facilitate the development and study of treatment interventions optimizing health, function, participation, and quality of life.

The cerebral palsy research network: Building a learning health network for cerebral palsy.

PURPOSE: The purpose of this study was to measure the growth of the Cerebral Palsy (CP) Research Network towards becoming a Learning Health Network in order to guide future development. METHODS: Thirteen CP Research Network leaders completed the Network Maturity Grid (NMG) which consists of six domains with eight to 10 components each. The six domains are Systems of Leadership, Governance and Management, Quality Improvement, Engagement and Community, Data and Analytics, and Research. Radar mapping was utilized to display mean scores on a 5-point ordinal scale (1 = not started to 5 = idealized state) across domains and for individual components within domains. Consensus was reached for top priorities for the next 3-5 years. RESULTS: Domain scores ranged from 2.4 in Quality Improvement to 3.2 in System of Leadership. The lowest scoring component was clinician clinical decision support and the highest was common purpose. The following priority areas of focus were agreed upon moving forward: development of leaders, financial sustainability, quality improvement education and training, patient reported data, data quality and validation, and primary data collection. CONCLUSION: Results from this project will be utilized for strategic planning to improve the network. Conducting regular self-assessments of the network with the NMG will be useful in achieving the network's ultimate goal to improve care and outcomes for individuals with CP.

Registry-based Research in Cerebral Palsy: The Cerebral Palsy Research Network.

Registries are a powerful tool for clinical research. Clinical registries for cerebral palsy can aid in comparative effectiveness research, especially using the practice-based evidence model. The Cerebral Palsy Research Network (CPRN) was initiated in 2014 as a patient-centered, multidisciplinary registry. The leadership group initiated a 4-stage participatory action research process: listen, reflect, plan/analyze, and take action. CPRN also joined with CP NOW, an advocacy group, to create a research agenda for cerebral palsy. With more than 20 centers and growing, CPRN hopes to generate evidence for developing best practices and measure their implementation and impact for individuals with cerebral palsy throughout North America.

Synthesis of glycosyl amino acids by light-induced coupling of photoreactive amino acids with glycosylamines and 1-C-aminomethyl glycosides.

The glycosylamines of O-acetyl-protected GlcNAc and chitobiose, as well as two partially unprotected 1-C-aminomethyl glucosides, were photochemically coupled with orthogonally protected N-aspartyl-5-bromo-7-nitroindoline derivatives. The reactions proceeded under neutral conditions by irradiation with near-UV light. The glycosyl asparagines with N- or C-glycosyl linkages were afforded in 60-85% yield on a 10-70 mg scale. Moreover, the ability of a highly photoreactive N-glutamyl-4-methoxy-7-nitroindoline derivative to acylate amino saccharides was tested. Upon irradiation in the presence of a dimeric 1-C-aminomethyl glycoside, or a glycosylamine, the corresponding glycosyl glutamines were obtained in 50% and 30% yield, respectively. Preparations of the photoreactive aspartates and the 1-C-aminomethyl glycosides are also described.

An update on research priorities in hydrocephalus: overview of the third National Institutes of Health-sponsored symposium "Opportunities for Hydrocephalus Research: Pathways to Better Outcomes".

Building on previous National Institutes of Health-sponsored symposia on hydrocephalus research, "Opportunities for Hydrocephalus Research: Pathways to Better Outcomes" was held in Seattle, Washington, July 9-11, 2012. Plenary sessions were organized into four major themes, each with two subtopics: Causes of Hydrocephalus (Genetics and Pathophysiological Modifications); Diagnosis of Hydrocephalus (Biomarkers and Neuroimaging); Treatment of Hydrocephalus (Bioengineering Advances and Surgical Treatments); and Outcome in Hydrocephalus (Neuropsychological and Neurological). International experts gave plenary talks, and extensive group discussions were held for each of the major themes. The conference emphasized patient-centered care and translational research, with the main objective to arrive at a consensus on priorities in hydrocephalus that have the potential to impact patient care in the next 5 years. The current state of hydrocephalus research and treatment was presented, and the following priorities for research were recommended for each theme. 1) Causes of Hydrocephalus-CSF absorption, production, and related drug therapies; pathogenesis of human hydrocephalus; improved animal and in vitro models of hydrocephalus; developmental and macromolecular transport mechanisms; biomechanical changes in hydrocephalus; and age-dependent mechanisms in the development of hydrocephalus. 2) Diagnosis of Hydrocephalus-implementation of a standardized set of protocols and a shared repository of technical information; prospective studies of multimodal techniques including MRI and CSF biomarkers to test potential pharmacological treatments; and quantitative and cost-effective CSF assessment techniques. 3) Treatment of Hydrocephalus-improved bioengineering efforts to reduce proximal catheter and overall shunt failure; external or implantable diagnostics and support for the biological infrastructure research that informs these efforts; and evidence-based surgical standardization with longitudinal metrics to validate or refute implemented practices, procedures, or tests. 4) Outcome in Hydrocephalus-development of specific, reliable batteries with metrics focused on the hydrocephalic patient; measurements of neurocognitive outcome and quality-of-life measures that are adaptable, trackable across the growth spectrum, and applicable cross-culturally; development of comparison metrics against normal aging and sensitive screening tools to diagnose idiopathic normal pressure hydrocephalus against appropriate normative age-based data; better understanding of the incidence and prevalence of hydrocephalus within both pediatric and adult populations; and comparisons of aging patterns in adults with hydrocephalus against normal aging patterns.

Palladium-charcoal-catalyzed reduction of tri-O-acetyl-beta-L-fucopyranosyl cyanide: a route to small cluster oligosaccharide mimetics (SCOMs).

[reaction: see text] Synthesis of glycosyl cyanides was optimized with a new catalyst system. Reduction of tri-O-acetyl-beta-L-fucopyranosyl cyanide with Pd-hydrogen, in the presence of Ac(2)O and Boc(2)O, gave N-protected-mono- and -di-(2,3,4-tri-O-acetyl-beta-L-fucopyranosylmethyl)-amines, which allow for the syntheses of small cluster oligosaccharide mimetics of fucopyranosylomethyl-substituted ureas. From di-(2,3,4-tri-O-acetyl-beta-L-fucopyranosylmethyl) amine was also prepared a carbamoyl chloride as a potentially useful synthon for preparation of more complex C-glycosidic conjugates.

C-H-deprotonation mediated by a remote syn-axial acetoxy group--an unprecedented double bond formation upon cyanation of the dimer from L-fucal.

Replacement of the anomeric acetate by a cyanide group in the dimer of di-O-acetyl-L-fucal by the action of mild Lewis acid [Hg(CN)(2)-HgBr(2)-Me(3)SiCN], resulted not only in the desired transformation but also in the introduction of an additional double bond between C-2A and C-3A. Due to its configuration, the remote C-4A acetoxy group may facilitate the deprotonation by functioning as an internal base. 1H NMR spectroscopy and X-ray crystallography indicate that the conformations of both rings A and B and their relative orientation in the resulting C-linked disaccharidic glycosyl cyanide, 4-O-acetyl-2-C-(4-O-acetyl-2,3-dideoxy-alpha-L-threo-hex-2-enopyranosyl)-2,3-dideoxy-2-eno-alpha-L-fucopyranosyl cyanide, in solution are virtually identical to the crystal structure.

Mild synthesis of disaccharidic 2,3-enopyranosyl cyanides and 2-C-2-deoxy pyranosyl cyanides with Hg(CN)(2)/HgBr(2)/TMSCN.

Lewis acid-catalyzed dimerization of mono- and disaccharidic per-O-acetylated glycals gave di- and tetrasaccharidic O-acetylated C-glycosides, respectively. 2,3-Enopyranosyl cyanides were obtained from per-O-acetylated glycals by a new, mild anomeric S(N)'-acetoxy displacement with Hg(CN)(2)/HgBr(2)/TMSCN. Per-O-acetylated 2-C-2-deoxy-pyranoses were converted into pyranosyl cyanides by the same reagent. An unprecedented acetic acid elimination from dimers with D-galacto- and L-fuco-configurations accompanied the S(N)-displacement under those conditions. A new set of (1)H NMR coupling constants for 2,3-enopyranosyl systems was used for configurational assignment of complicated tetrasaccharide mimics.