Transition from child to adult services for young people with cerebral palsy in Ireland: Influencing factors at multiple ecological levels.

AIM: To explore the factors that influence the process of transitioning from child to adult services in Ireland among young people with cerebral palsy, their parents, and service providers. METHOD: This study followed a qualitative descriptive approach. Semi-structured interviews were conducted with 54 participants, including young people with cerebral palsy aged 16 to 22 years (n = 13), their parents (n = 14), and service providers (n = 27). Data were analysed using the Framework Method. Findings were categorized using an ecological model across four levels: individual, microsystem, mesosystem, and exosystem. RESULTS: Limited awareness, preparation, and access to information hindered successful transition. Microsystem factors such as family knowledge, readiness, resilience, and health professional expertise influenced transition experience. Mesosystem factors encompassed provider-family interaction, interprofessional partnerships, and interagency collaboration between child and adult services. Exosystem factors included inadequate availability and distribution of adult services, limited referral options, coordination challenges, absence of transition policies, staffing issues, and funding allocation challenges. INTERPRETATION: Transition is influenced by diverse factors at multiple ecological levels, including interactions within families, between health professionals, and larger systemic factors. Given the complexity of transition, a comprehensive multi-level response is required, taking into account the interactions among individuals, services, and systems.

Understanding the use of digital technologies to provide disability services remotely during the COVID-19 pandemic; a multiple case study design.

BACKGROUND: Using digital technologies to provide services and supports remotely may improve efficiency and accessibility of healthcare, and support people with disabilities to live independently. This study aimed to explore the experience of using digital technologies to access and provide disability services and supports during the Covid-19 pandemic, from the perspective of people with disabilities, families and service providers. METHODS: Using a multiple case study design, we purposively sampled three cases based on service user characteristics and geographical reach of the service. We conducted semi-structured interviews with 40 service users and service providers. Topic guides and analysis were informed by the Consolidated Framework for Implementation Research (CFIR). Analysis followed a largely deductive approach, using the CFIR constructs as a coding framework. A summary memo was developed for each case. Influence and strength of each construct was rated to identify constructs that influenced implementation of digital technologies. Ratings were compared across services to identify facilitators and barriers to implementation. RESULTS: Service users and providers were positive about using digital technologies to access and provide disability services and supports remotely. Advantages over in-person delivery included reduced travel time, increased opportunity for peer support and peer learning, more choice and opportunity to participate in activities, and an enhanced sense of self while accessing services from the secure environment of their home. The urgency to identify new modes of service delivery to meet the needs of service users during Covid-19 was a strong facilitator but did not necessarily result in successful implementation. Other factors that were strong facilitators were the use of adaptations to enable service users to access the online service, service users' willingness to try the online service, service users' persistence when they encountered challenges, and the significant time and effort that service providers made to support service users to participate in the online service. Barriers to implementation included the complexity of accessing online platforms, poor design quality of online platforms, and organisations prioritising in-person delivery over online services. CONCLUSIONS: These findings may allow service providers to leverage facilitators that support implementation of online disability services and supports.

Transition to adult services experienced by young people with cerebral palsy: A cross-sectional study.

AIM: To assess if young people with cerebral palsy experience and health professionals provide practices that may improve transition from child to adult health services. METHOD: Seventy-five young people (31 females, 44 males; mean age 18 years 5 months [standard deviation 2 years 2 months]) and/or parents and 108 health professionals completed a questionnaire describing their experience or the provision of nine transition practices. RESULTS: The percentage of young people reporting each practice was: appropriate parent involvement (90%); promotion of health self-efficacy (37%); named worker who supports the transition process (36%); self-management support for physical health (36%); self-management support for mental health (17%); information about the transition process (24%); meeting the adult team (16%); and life skills training (16%). Post-discharge, 10% of young people reported that their general practitioner (GP) received a discharge letter. The percentage of health professionals reporting each practice was: promotion of health self-efficacy (73.2%); self-management support (73.2%); information (69%); consulting the parent and young person about parent involvement (63% and 66%); discharge letter to a GP (55%); life skills training (36%); named worker (35%); meeting the adult team (30%); and senior manager (20%). INTERPRETATION: Many young people did not experience practices that may improve the experience and outcomes of transition. Young people should be involved in the development and delivery of transition to ensure it meets their needs. WHAT THIS PAPER ADDS: Many young people with cerebral palsy (CP) do not receive support that may improve the experience of transition. Appropriate protocols and training for health professionals may improve the provision of transition and reduce inconsistency in care between and within organizations. Young people and their families should be involved in service design, delivery, and evaluation related to the transition to ensure it meets their needs.

Prevalence and incidence of chronic conditions among adults with cerebral palsy: A systematic review and meta-analysis.

AIM: To assess the prevalence and incidence of chronic conditions among adults with cerebral palsy (CP) and compare them to the prevalence and incidence among adults without CP. METHOD: We searched MEDLINE and Embase for studies reporting the prevalence or incidence of one or more chronic conditions among adults with CP. Two independent reviewers screened titles, abstracts, and full-text articles. Two independent reviewers extracted data relating to prevalence and incidence and appraised study quality. We performed random-effects meta-analyses to pool prevalence and incidence. RESULTS: We identified 69 studies; 65 reported the prevalence of 53 conditions and 13 reported the incidence of 21 conditions. At least 20% of adults had the following conditions: depression (21%); anxiety (21%); mood affective disorders (23%); asthma (24%); hypertension (26%); epilepsy (28%); urinary incontinence (32%); malnutrition (38%); and scoliosis (46%). Adults with CP were more likely to have type 2 diabetes, anxiety, bipolar disorder, depression, schizophrenia, hypertension, ischaemic heart disease, stroke, cerebrovascular disease, asthma, liver disease, osteoarthritis, osteoporosis, underweight, and chronic kidney disease than adults without CP. INTERPRETATION: These data from 18 countries, which provide an international perspective, may be used to promote awareness, identify targets for intervention, and inform the development of appropriate supports for adults with CP.

Interventions for improving adherence to airway clearance treatment and exercise in people with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a life-limiting genetic disorder predominantly affecting the lungs and pancreas. Airway clearance techniques (ACTs) and exercise therapy are key components of physiotherapy, which is considered integral in managing CF; however, low adherence is well-documented. Poor physiotherapy adherence may lead to repeated respiratory infections, reduced exercise tolerance, breathlessness, reduced quality of life, malaise and reduced life expectancy, as well as increased use of pharmacology, healthcare access and hospital admission. Therefore, evidence-based strategies to inform clinical practice and improve adherence to physiotherapy may improve quality of life and reduce treatment burden. OBJECTIVES: To assess the effects of interventions to enhance adherence to airway clearance treatment and exercise therapy in people with CF and their effects on health outcomes, such as pulmonary exacerbations, exercise capacity and health-related quality of life. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 1 March 2023. We also searched online trials registries and the reference lists of relevant articles and reviews. Date of last search: 28 March 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs of parallel design assessing any intervention aimed at enhancing adherence to physiotherapy in people with CF versus no intervention, another intervention or usual care. DATA COLLECTION AND ANALYSIS: Two review authors independently checked search results for eligible studies and independently extracted data. We used standard procedures recommended by Cochrane and assessed the certainty of evidence using the GRADE system. MAIN RESULTS: Two RCTs (77 participants with CF; age range 2 to 20 years; 44 (57%) males) met the inclusion criteria of this review. One study employed an intervention to improve adherence to exercise and the second an intervention to improve adherence to ACT. Both studies measured outcomes at baseline and at three months, but neither study formally assessed our primary outcome of adherence in terms of our planned outcome measures, and results were dependent on self-reported data. Adherence to ACTs One RCT (43 participants) assessed using specifically-composed music alongside ACTs compared to self-selected or no music (usual care). The ACT process consisted of nebuliser inhalation treatment, ACTs and relaxation or antibiotic nebuliser treatment. We graded all evidence as very low certainty. This study reported adherence to ACTs using the Morisky-Green questionnaire and also participants' perception of treatment time and enjoyment, which may influence adherence (outcome not reported specifically in this review). We are uncertain whether participants who received specifically-composed music may be more likely to adhere at six and 12 weeks compared to those who received usual care, risk ratio (RR) 1.75 (95% confidence interval (CI) 1.07 to 2.86) and RR 1.56 (95% CI 1.01 to 2.40) respectively. There may not be any difference in adherence when comparing specifically-composed music to self-selected music at six weeks, RR 1.21 (95% CI 0.87 to 1.68) or 12 weeks, RR 1.52 (95% CI 0.97 to 2.38); or self-selected music to usual care at six weeks, RR 1.44 (95% CI 0.82 to 2.52) or 12 weeks, RR 1.03 (95% CI 0.57 to 1.86). The music study also reported the number of respiratory infections requiring hospitalisation at 12 weeks, with no difference seen in the risk of hospitalisation between all groups. Adherence to exercise One RCT (24 participants) compared the provision of a manual of aerobic exercises, recommended exercise prescription plus two-weekly follow-up phone calls to reinforce exercise practice over a period of three months to verbal instructions for aerobic exercise according to the CF centre's protocol. We graded all evidence as very low certainty. We are uncertain whether an educational intervention leads to more participants in the intervention group undertaking increased regular physical activity at three months (self-report), RR 3.67 (95% CI 1.24 to 10.85), and there was no reported difference between groups in the number undertaking physical activity three times per week or undertaking at least 40 minutes of physical activity. No effect was seen on secondary outcome measures of spirometry, exercise capacity or any CF quality of life domains. This study did not report on the frequency of respiratory infections (hospitalised or not) or adverse events. AUTHORS' CONCLUSIONS: We are uncertain whether a music-based motivational intervention may increase adherence to ACTs or affect the risk of hospitalisation for a respiratory infection. We are also uncertain whether an educational intervention increases adherence to exercise or reduces the frequency of respiratory infection-related hospital admission. However, these results are largely based on self-reported data and the impact of strategies to improve adherence to ACT and exercise in children and adolescents with stable CF remains inconclusive. Given that adherence to ACT and exercise therapy are fundamental to the clinical management of people with CF, there is an urgent need for well-designed, large-scale clinical trials in this area, which should conform to the CONSORT statement for standards of reporting and use appropriate, validated outcome measures. Studies should also ensure full disclosure of data for all important clinical outcomes.

Health service use among adults with cerebral palsy: a mixed-methods systematic review.

AIM: To determine the proportion of adults with cerebral palsy (CP) using health services and frequency of use, and to explore experiences and perceptions of health services for this population. METHOD: A mixed-methods systematic review was conducted using the Joanna Briggs Institute methodology. Five databases were searched to September 2020. Observational and qualitative studies were included. Two reviewers screened titles, abstracts, and full texts; extracted data; and assessed the quality of included studies. Separate meta-analyses were used to pool the proportion of adults using each service and frequency of use. A meta-aggregation approach was used to synthesize qualitative data. Quantitative and qualitative findings were integrated using the Andersen and Newman Model of health care utilization. RESULTS: Fifty-seven studies (31 quantitative, 26 qualitative) of 14 300 adults with CP were included. The proportion of adults using services ranged from 7% (95% confidence interval [CI]: 2-13%) for urologists to 84% (95% CI: 78-90%) for general practitioners. Incidence of visits ranged from 67 (95% CI: 37-123) hospital admissions to 404 (95% CI: 175-934) general practitioner visits per 100 person-years. Qualitative themes highlighted issues regarding accessibility, caregivers' involvement, health workers' expertise, unmet ageing needs, transition, and health system challenges. INTERPRETATION: Adults with CP used a wide range of health services but faced context-specific challenges in accessing required care. Appropriate service delivery models for adults with CP are required. This review emphasizes a need to develop an appropriate service model for adults with CP to meet their needs.

Guidelines on the management of ascites in cirrhosis.

The British Society of Gastroenterology in collaboration with British Association for the Study of the Liver has prepared this document. The aim of this guideline is to review and summarise the evidence that guides clinical diagnosis and management of ascites in patients with cirrhosis. Substantial advances have been made in this area since the publication of the last guideline in 2007. These guidelines are based on a comprehensive literature search and comprise systematic reviews in the key areas, including the diagnostic tests, diuretic use, therapeutic paracentesis, use of albumin, transjugular intrahepatic portosystemic stent shunt, spontaneous bacterial peritonitis and beta-blockers in patients with ascites. Where recent systematic reviews and meta-analysis are available, these have been updated with additional studies. In addition, the results of prospective and retrospective studies, evidence obtained from expert committee reports and, in some instances, reports from case series have been included. Where possible, judgement has been made on the quality of information used to generate the guidelines and the specific recommendations have been made according to the 'Grading of Recommendations Assessment, Development and Evaluation (GRADE)' system. These guidelines are intended to inform practising clinicians, and it is expected that these guidelines will be revised in 3 years' time.

Safety, feasibility, acceptability and effects of a behaviour-change intervention to change physical activity behaviour among people with multiple sclerosis: Results from the iStep-MS randomised controlled trial.

BACKGROUND: There is limited information regarding the safety, feasibility and acceptability of behaviour-change interventions to increase physical activity (PA) and reduce sedentary behaviour among people with multiple sclerosis (MS). Prior to evaluating efficacy, it is important to identify problems with feasibility and acceptability, which may undermine effectiveness. OBJECTIVE: To examine the safety, feasibility and acceptability of a behaviour-change intervention to increase PA and reduce sedentary behaviour among people with MS. METHODS: Sixty people received a 3-month intervention or usual care. Fatigue, pain and adverse events (AEs) were assessed. Feasibility and acceptability were explored through focus groups with physiotherapists and interviews with participants. Fidelity to intervention content, delivery skills, programme receipt and programme task were assessed. RESULTS: There was no difference in AE rate between groups (p = 0.965). Fatigue and pain were not higher in the intervention group at 3 or 9 months. Therapists reported the intervention was feasible to deliver and fidelity was acceptable. Twenty-nine participants (97%) attended at least 75% of sessions. Participants found the intervention acceptable but suggested some amendments were required to intervention components. CONCLUSIONS: The intervention was safe, feasible and acceptable. Although modifications are required to intervention components, the intervention warrants further evaluation in a future trial.

Progressive resistance training for adolescents with cerebral palsy: the STAR randomized controlled trial.

AIM: To evaluate the effect of progressive resistance training of the ankle plantarflexors on gait efficiency, activity, and participation in adolescents with cerebral palsy (CP). METHOD: Sixty-four adolescents (10-19y; 27 females, 37 males; Gross Motor Function Classification System [GMFCS] levels I-III) were randomized to 30 sessions of resistance training (10 supervised and 20 unsupervised home sessions) over 10 weeks or usual care. The primary outcome was gait efficiency indicated by net nondimensional oxygen cost (NNcost). Secondary outcomes included physical activity, gross motor function, participation, muscle strength, muscle and tendon size, and muscle and tendon stiffness. Analysis was intention-to-treat. RESULTS: Median attendance at the 10 supervised sessions was 80% (range 40-100%). There was no between-group difference in NNcost at 10 (mean difference: 0.02, 95% confidence interval [CI] -0.07 to 0.11, p=0.696) or 22 weeks (mean difference: -0.08, 95% CI -0.18 to 0.03, p=0.158). There was also no evidence of between-group differences in secondary outcomes at 10 or 22 weeks. There were 123 adverse events reported by 27 participants in the resistance training group. INTERPRETATION: We found that 10 supervised sessions and 20 home sessions of progressive resistance training of the ankle plantarflexors did not improve gait efficiency, muscle strength, activity, participation, or any biomechanical outcome among adolescents with CP. WHAT THIS PAPER ADDS: Thirty sessions of progressive resistance training of the ankle plantarflexors over 10 weeks did not improve gait efficiency among ambulatory adolescents with cerebral palsy. Resistance training did not improve muscle strength, activity, or participation. Ninety percent of participants experienced an adverse event. Most adverse events were expected and no serious adverse events were reported.

Incidence of falls among adults with cerebral palsy: a cohort study using primary care data.

AIM: To compare the rate of falls between adults with and without cerebral palsy (CP). METHOD: We used primary care data on 1705 adults with CP and 5115 adults without CP matched for age, sex, and general practice attended. We compared odds of experiencing a fall between adults with and without CP using conditional logistic regression. We compared the rate of falls using a negative binomial model. RESULTS: Participants were 3628 males (53%) and 3192 females (47%) (median age 29y, interquartile range 20-42y) at the start of follow-up. Follow-up was 14 617 person-years for adults with CP and 56 816 person-years for adults without CP. Of adults with CP, 15.3% experienced at least one fall compared to 5.7% of adults without CP. Adults with CP had 3.64 times (95% confidence interval [CI] 2.98-4.45) the odds of experiencing a fall compared to adults without CP. The rate of falls was 30.5 per 1000 person-years and 6.7 per 1000 person-years for adults with and without CP respectively (rate ratio 5.83, 95% CI 4.84-7.02) INTERPRETATION: Adults with CP are more likely to fall, and fall more often, than adults without CP. The causes and consequences of falls in adults with CP need examination. WHAT THIS PAPER ADDS: Twenty adults with CP and 5.3 adults without CP experienced at least one fall per 1000 person-years. Adults with CP experienced 30.5 falls per 1000 person-years compared to 6.7 falls per 1000 person-years among adults without CP. Adults with CP had 3.64 times the odds of experiencing a fall compared to adults without CP. Adults with CP experienced 5.83 times more falls than adults without CP.

The use and perception of support walkers for children with disabilities: a United Kingdom survey.

BACKGROUND: Support walkers are a type of assistive device that may enable non-ambulant children with disabilities to walk independently and promote improvements in bowel function, bone mineral density (BMD), mobility, independence, participation and social function. However, there is little evidence to support these benefits and there is a lack of research describing the use of support walkers in clinical practice. This study aimed to examine the use of support walkers for children with disabilities in clinical practice. METHOD: A survey was distributed via professional organisations, charities and schools associated with paediatric disabilities in the UK. Participants were recruited between January and March 2018. Populations of interest were those who prescribe support walkers to children with disabilities and those who work with children who use them. RESULTS: In total, 125 people were included in the analysis; 107 responders prescribed support walkers and 18 responders worked with children who used support walkers. The population of children who use support walkers ranged from 6 months to 18 years and included children with cerebral palsy, chromosomal abnormalities and other medical conditions. Use of these devices was also reported in schools, at home and in the community for varying lengths of time. Numerous perceived benefits were noted, most frequent of which were increases in physical activity and enjoyment. By comparison, fewer perceived problems were identified but centred on lack of space and difficulty with transfers. CONCLUSIONS: This study provides insight into the use of support walkers in the UK, particularly surrounding current practices, which may help to improve consistency in clinical settings. Perceived benefits and problems may provide a basis for identification of appropriate outcome measures to monitor effectiveness. These results should also provide a basis for designing future studies to examine effectiveness of support walkers for paediatric disabilities.

Mortality due to cardiovascular disease, respiratory disease, and cancer in adults with cerebral palsy.

AIM: To compare mortality rates for cardiovascular disease, cancer, and respiratory disease between adults with cerebral palsy (CP) and the general population. METHOD: A cohort study was conducted using data from adults with CP in England, identified through a primary care data set (the Clinical Practice Research Datalink), with linked data on death registrations from the Office for National Statistics. Cause of death was categorized according to International Classification of Diseases codes. Standardized mortality ratios (SMRs) were calculated to compare mortality rates between adults with CP and the general population, adjusted for age, sex, and calendar year. RESULTS: Nine hundred and fifty-eight adults with CP were identified (52.5% males, 47.5% females; median age at start of follow-up 31y [interquartile range 22-43y]) and followed for a total of 7693 person-years. One hundred and forty-two patients (15%) died during follow-up. Adults with CP had an increased risk of death due to cardiovascular disease (SMR: 3.19, 95% confidence interval [CI] 2.20-4.62) and respiratory disease (SMR: 13.59, 95% CI 9.89-18.67), but not from malignant neoplasms (SMR: 1.42, 95% CI 0.83-2.45). INTERPRETATION: We found that adults with CP in England have increased risk of death due to diseases of the circulatory and respiratory systems, supporting findings from two studies that compared cause-specific mortality rates between adults with CP in the USA and the general population. Further research is required into primary and secondary prevention of cardiovascular and respiratory disease in people with CP worldwide. WHAT THIS PAPER ADDS: Adults with cerebral palsy (CP) in England have 14-fold increased risk of mortality due to diseases of the respiratory system. They have a 3-fold increased risk of mortality due to diseases of the circulatory system. Adults with CP had an increased risk of death due to cerebrovascular disease and ischaemic heart disease. The elevated risk of ischaemic heart disease, however, did not reach statistical significance at the 5% per cent level.

MORTALIDAD POR ENFERMEDAD CARDIOVASCULAR, ENFERMEDAD RESPIRATORIA Y CÁNCER EN ADULTOS CON PARÁLISIS CEREBRAL: OBJETIVO: Comparar tasas de mortalidad por enfermedad cardiovascular, cáncer y enfermedad respiratoria entre adultos con parálisis cerebral (PC) y la población general. MÉTODO: Se llevó a cabo un estudio de cohorte utilizando datos de adultos con PC en Inglaterra, identificados a través de un set de datos de atención primaria (the Clinical Practice Research Datalink) con datos vinculados sobre los registros de defunciones de la Oficina Nacional de Estadísticas. Las causas de muertes fueron categorizadas de acuerdo con los códigos de la Clasificación Internacional de Enfermedades. Las tasas de mortalidad estandarizadas (TME) fueron calculadas a fin de comparar las tasas de mortalidad entre adultos con PC y la población general, ajustadas por edad, sexo y año calendario. RESULTADOS: Se identificaron 958 adultos con PC (52,5% varones, 47,5% mujeres; edad mediana al comienzo del seguimiento 31 años [rango intercuartilo 22-43 años] y fueron seguidos por un total de 7.693 años-persona. Ciento cuarenta y dos pacientes (15%) fallecieron durante el seguimiento. Los adultos con PC tuvieron un mayor riesgo de muerte por enfermedad cardiovascular (TME:3,19, 95% intervalo de confidencia [IC] 2,20-4,62) y enfermedad respiratoria (TME:13,59,95% IC 9,89-18,67), pero no tuvieron mayor riesgo de neoplasias malignas (TME:1,42, 95% IC 0,83-2,45). INTERPRETACIÓN: Encontramos que los adultos con PC en Inglaterra tienen un riesgo incrementado de muerte por enfermedades de los sistemas circulatorio y respiratorio, sosteniendo los hallazgos con dos estudios que compararon tasas de mortalidad causa-específicas entre adultos con PC en los EEUU y la población general. Se necesita avanzar con la investigación hacia prevención primaria y secundaria de enfermedades cardiovascular y respiratoria en personas con PC en todo el mundo.

MORTALIDADE DEVIDO A DOENÇA CARDIOVASCULAR, RESPIRATÓRIA, E CÂNCER EM ADULTOS COM PARALISIA CEREBRAL: OBJETIVO: Comparar as taxas de mortalidade por doença cardiovascular, câncer, e doença respiratória em adultos com paralisia cerebral (PC) e a população em geral. MÉTODO: Um estudo de coorte foi realizado usando dados de adultos com PC na Inglaterra, identificados por meio de um conjunto de dados de atenção primária (o Datalink Pesquisa em Prática Clínica,), com dados sobre registros de óbitos do Escritório Nacional de Estatística. A causa da morte foi categorizada de acordo com os códigos da Classificação Internacional de Doenças. Taxas de mortalidade padronizadas (TMPs) foram calculadas para comparar as taxas de mortalidade entre adultos com PC e a população em geral, ajustadas por idade, sexo e ano calendário. RESULTADOS: Novecentos e cinquenta e oito adultos com PC foram identificados (52,5% do sexo masculino, 47,5% do sexo feminino; idade mediana no início do acompanhamento 31a [intervalo interquartil 22-43a]) e acompanhados por um total de 7,693 anos-pessoa. Cento e quarenta e dois pacientes (15%) morreram durante o acompanhamento. Adultos com PC tiveram risco aumentado de morte por doença (TMP: 3,19, intervalo de confiança [IC] a 95% 2,20-4,62) e doença respiratória (TMP: 13,59, IC 95% 9,89-18,67), mas não por neoplasias malignas (TMP: 1,42, IC 95% 0,83-2,45). INTERPRETAÇÃO: Observamos que adultos com PC na Inglaterra têm risco aumentado de more por doenças dos sistemas circulatório e respiratório, o que apóia achados de dois estudos qu compararam taxas de mortalidade causa-específica em adultos com PC nos EUA e na população em geral. Mais pesquisas são necessárias sobre a prevenção primária e secundária de doenças cardiovasculares e respiratórias em pessoas com PC em todo o mundo.

Mucosa-associated invariant T cells link intestinal immunity with antibacterial immune defects in alcoholic liver disease.

BACKGROUND/AIMS: Intestinal permeability with systemic distribution of bacterial products are central in the immunopathogenesis of alcoholic liver disease (ALD), yet links with intestinal immunity remain elusive. Mucosa-associated invariant T cells (MAIT) are found in liver, blood and intestinal mucosa and are a key component of antibacterial host defences. Their role in ALD is unknown. METHODS/DESIGN: We analysed frequency, phenotype, transcriptional regulation and function of blood MAIT cells in severe alcoholic hepatitis (SAH), alcohol-related cirrhosis (ARC) and healthy controls (HC). We also examined direct impact of ethanol, bacterial products from faecal extracts and antigenic hyperstimulation on MAIT cell functionality. Presence of MAIT cells in colon and liver was assessed by quantitative PCR and immunohistochemistry/gene expression respectively. RESULTS: In ARC and SAH, blood MAIT cells were dramatically depleted, hyperactivated and displayed defective antibacterial cytokine/cytotoxic responses. These correlated with suppression of lineage-specific transcription factors and hyperexpression of homing receptors in the liver with intrahepatic preservation of MAIT cells in ALD. These alterations were stronger in SAH, where surrogate markers of bacterial infection and microbial translocation were higher than ARC. Ethanol exposure in vitro, in vivo alcohol withdrawal and treatment with Escherichia coli had no effect on MAIT cell frequencies, whereas exposure to faecal bacteria/antigens induced functional impairments comparable with blood MAIT cells from ALD and significant MAIT cell depletion, which was not observed in other T cell compartments. CONCLUSIONS: In ALD, the antibacterial potency of MAIT cells is compromised as a consequence of contact with microbial products and microbiota, suggesting that the 'leaky' gut observed in ALD drives MAIT cell dysfunction and susceptibility to infection in these patients.

The risk, burden, and management of non-communicable diseases in cerebral palsy: a scoping review.

AIM: To examine the risk, burden, and management of non-communicable diseases (NCDs) among people with cerebral palsy (CP). METHOD: Databases (Ovid MEDLINE, Embase Ovid, CINAHL Plus) were systematically searched up to August 2017. Data on the prevalence of risk factors for, and the burden and management of, cardiovascular diseases, diabetes, cancers, and respiratory diseases were extracted. RESULTS: Thirty-six studies that examined the prevalence of risk factors among people with CP were identified. There was inconsistent evidence that people with CP had higher prevalence of metabolic risk factors such as hypertension, hyperlipidaemia, and obesity, but strong evidence that they participated in low levels of physical activity, compared with people without CP. Seven studies reported on the burden of NCDs. Adults with CP had a higher risk of NCDs, including stroke, chronic obstructive pulmonary disease, and other heart conditions, and death due to NCDs, including cancers, chronic obstructive pulmonary disease, stroke, and ischaemic heart disease, compared with the general population. Only one study reported on the management of NCD, specifically the uptake of breast cancer screening among females. INTERPRETATION: The burden of NCDs is higher among adults with CP compared with the general population. Further research is required to determine the prevalence of metabolic risk factors and management of NCDs among people with CP. WHAT THIS PAPER ADDS: Adults with cerebral palsy (CP) have an increased risk of non-communicable diseases (NCDs) and increased risk of death because of NCDs. Evidence is inconsistent about the elevated prevalence of metabolic risk factors for NCDs. Evidence is consistent that people with CP participate in reduced physical activity. Only one study reported on management of NCD among people with CP. Available evidence suggests people with CP are less likely to receive preventive medicine.

Interventions to Improve or Maintain Lower-Limb Function Among Ambulatory Adolescents with Cerebral Palsy: A Cross-Sectional Survey of Current Practice in the UK.

OBJECTIVES: To describe physiotherapy management to improve or maintain lower-limb function among adolescents with cerebral palsy, classified in Gross Motor Function Classification System levels I-III, in the United Kingdom (UK). METHODS: A list of interventions was identified using a nominal group technique and developed into a survey, which was distributed to approximately 2,100 pediatric physiotherapists in the UK through the Association of Pediatric Chartered Physiotherapists and a private physiotherapy clinic in London between April and June 2015. One-hundred and thirty-five physiotherapists completed the survey. Survey respondents indicated how frequently they used each intervention (i.e., "frequently," "sometimes," "rarely," and "never") in the past year. RESULTS: Provision of explanations to the child, liaison with families, liaison with health professionals, provision of advice to schools, and stretching were the most frequently used interventions with 90%, 90%, 86%, 79%, and 76% of respondents, respectively, reporting that they frequently used each. The interventions most commonly reported as "never" used were conductive education (88%), MOVE programme (85%), functional electrical stimulation (82%), body-weight supported treadmill training (80%), and rebound therapy (71%). CONCLUSIONS: This study suggests that a large number of interventions are used by physiotherapists in the United Kingdom to improve or maintain lower-limb function among adolescents with CP, not all of which are evidence-based.

Defective monocyte oxidative burst predicts infection in alcoholic hepatitis and is associated with reduced expression of NADPH oxidase.

OBJECTIVE: In order to explain the increased susceptibility to serious infection in alcoholic hepatitis, we evaluated monocyte phagocytosis, aberrations of associated signalling pathways and their reversibility, and whether phagocytic defects could predict subsequent infection. DESIGN: Monocytes were identified from blood samples of 42 patients with severe alcoholic hepatitis using monoclonal antibody to CD14. Phagocytosis and monocyte oxidative burst (MOB) were measured ex vivo using flow cytometry, luminometry and bacterial killing assays. Defects were related to the subsequent development of infection. Intracellular signalling pathways were investigated using western blotting and PCR. Interferon-γ (IFN-γ) was evaluated for its therapeutic potential in reversing phagocytic defects. Paired longitudinal samples were used to evaluate the effect of in vivo prednisolone therapy. RESULTS: MOB, production of superoxide and bacterial killing in response to Escherichia coli were markedly impaired in patients with alcoholic hepatitis. Pretreatment MOB predicted development of infection within two weeks with sensitivity and specificity that were superior to available clinical markers. Accordingly, defective MOB was associated with death at 28 and 90 days. Expression of the gp91 phox subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase was reduced in patients with alcoholic hepatitis demonstrating defective MOB. Monocytes were refractory to IFN-γ stimulation and showed high levels of a negative regulator of cytokine signalling, suppressor of cytokine signalling-1. MOB was unaffected by 7 days in vivo prednisolone therapy. CONCLUSIONS: Monocyte oxidative burst and bacterial killing is impaired in alcoholic hepatitis while bacterial uptake by phagocytosis is preserved. Defective MOB is associated with reduced expression of NADPH oxidase in these patients and predicts the development of infection and death.

Dysfunctional neutrophil effector organelle mobilization and microbicidal protein release in alcohol-related cirrhosis.

Patients with alcohol-related cirrhosis (ALD) are prone to infection. Circulating neutrophils in ALD are dysfunctional and predict development of sepsis, organ dysfunction, and survival. Neutrophil granules are important effector organelles containing a toxic array of microbicidal proteins, whose controlled release is required to kill microorganisms while minimizing inflammation and damage to host tissue. We investigated the role of these granular responses in contributing to immune disarray in ALD. Neutrophil granular content and mobilization were measured by flow cytometric quantitation of cell-surface/intracellular markers, [secretory vesicles (CD11b), secondary granules (CD66b), and primary granules (CD63; myeloperoxidase)] before and after bacterial stimulation in 29 patients with ALD cirrhosis (15 abstinent; 14 actively drinking) compared with healthy controls (HC). ImageStream Flow Cytometry characterized localization of granule subsets within the intracellular and cell-surface compartments. The plasma cytokine environment was analyzed using ELISA/cytokine bead array. Circulating neutrophils were primed in the resting state with upregulated surface expression of CD11b (P = 0.0001) in a cytokine milieu rich in IL-8 (P < 0.001) and lactoferrin (P = 0.035). Neutrophils showed exaggerated mobilization to the cell surface of primary granules at baseline (P = 0.001) and in response to N-formyl-l-methionyl-l-leucyl-l-phenylalanine (P = 0.009) and Escherichia coli (P = 0.0003) in ALD. There was no deficit in granule content or mobilization to the cell membrane in any granule subset observed. Paradoxically, active alcohol consumption abrogated the hyperresponsive neutrophil granular responses compared with their abstinent counterparts. Neutrophils are preprimed at baseline with augmented effector organelle mobilization in response to bacterial stimulation; neutrophil degranulation is not a mechanism leading to innate immunoparesis in ALD.NEW & NOTEWORTHY Neutrophil granule release is dysregulated in patients with alcohol-related cirrhosis (ALD) with augmented effector organelle mobilization and microbiocidal protein release. Neutrophil granules are upregulated in ALD at baseline and demonstrate augmented responses to bacterial challenge. The granular responses in ALD did not contribute to the observed functional deficit in innate immunity but rather were dysregulated and hyperresponsive, which may induce bystander damage to host tissue. Paradoxically, active alcohol consumption abrogated the excessive neutrophil granular responses to bacterial stimulus compared with their abstinent counterparts.

Exercise interventions for cerebral palsy.

BACKGROUND: Cerebral palsy (CP) is a neurodevelopmental disorder resulting from an injury to the developing brain. It is the most common form of childhood disability with prevalence rates of between 1.5 and 3.8 per 1000 births reported worldwide. The primary impairments associated with CP include reduced muscle strength and reduced cardiorespiratory fitness, resulting in difficulties performing activities such as dressing, walking and negotiating stairs.Exercise is defined as a planned, structured and repetitive activity that aims to improve fitness, and it is a commonly used intervention for people with CP. Aerobic and resistance training may improve activity (i.e. the ability to execute a task) and participation (i.e. involvement in a life situation) through their impact on the primary impairments of CP. However, to date, there has been no comprehensive review of exercise interventions for people with CP. OBJECTIVES: To assess the effects of exercise interventions in people with CP, primarily in terms of activity, participation and quality of life. Secondary outcomes assessed body functions and body structures. Comparators of interest were no treatment, usual care or an alternative type of exercise intervention. SEARCH METHODS: In June 2016 we searched CENTRAL, MEDLINE, Embase, nine other databases and four trials registers. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs of children, adolescents and adults with CP. We included studies of aerobic exercise, resistance training, and 'mixed training' (a combination of at least two of aerobic exercise, resistance training and anaerobic training). DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts and potentially relevant full-text reports for eligibility; extracted all relevant data and conducted 'Risk of bias' and GRADE assessments. MAIN RESULTS: We included 29 trials (926 participants); 27 included children and adolescents up to the age of 19 years, three included adolescents and young adults (10 to 22 years), and one included adults over 20 years. Males constituted 53% of the sample. Five trials were conducted in the USA; four in Australia; two in Egypt, Korea, Saudi Arabia, Taiwan, the Netherlands, and the UK; three in Greece; and one apiece in India, Italy, Norway, and South Africa.Twenty-six trials included people with spastic CP only; three trials included children and adolescents with spastic and other types of CP. Twenty-one trials included people who were able to walk with or without assistive devices, four trials also included people who used wheeled mobility devices in most settings, and one trial included people who used wheeled mobility devices only. Three trials did not report the functional ability of participants. Only two trials reported participants' manual ability. Eight studies compared aerobic exercise to usual care, while 15 compared resistance training and 4 compared mixed training to usual care or no treatment. Two trials compared aerobic exercise to resistance training. We judged all trials to be at high risk of bias overall.We found low-quality evidence that aerobic exercise improves gross motor function in the short term (standardised mean difference (SMD) 0.53, 95% confidence interval (CI) 0.02 to 1.04, N = 65, 3 studies) and intermediate term (mean difference (MD) 12.96%, 95% CI 0.52% to 25.40%, N = 12, 1 study). Aerobic exercise does not improve gait speed in the short term (MD 0.09 m/s, 95% CI -0.11 m/s to 0.28 m/s, N = 82, 4 studies, very low-quality evidence) or intermediate term (MD -0.17 m/s, 95% CI -0.59 m/s to 0.24 m/s, N = 12, 1 study, low-quality evidence). No trial assessed participation or quality of life following aerobic exercise.We found low-quality evidence that resistance training does not improve gross motor function (SMD 0.12, 95% CI -0.19 to 0.43, N = 164, 7 studies), gait speed (MD 0.03 m/s, 95% CI -0.02 m/s to 0.07 m/s, N = 185, 8 studies), participation (SMD 0.34, 95% CI -0.01 to 0.70, N = 127, 2 studies) or parent-reported quality of life (MD 12.70, 95% CI -5.63 to 31.03, n = 12, 1 study) in the short term. There is also low-quality evidence that resistance training does not improve gait speed (MD -0.03 m/s, 95% CI -0.17 m/s to 0.11 m/s, N = 84, 3 studies), gross motor function (SMD 0.13, 95% CI -0.30 to 0.55, N = 85, 3 studies) or participation (MD 0.37, 95% CI -6.61 to 7.35, N = 36, 1 study) in the intermediate term.We found low-quality evidence that mixed training does not improve gross motor function (SMD 0.02, 95% CI -0.29 to 0.33, N = 163, 4 studies) or gait speed (MD 0.10 m/s, -0.07 m/s to 0.27 m/s, N = 58, 1 study) but does improve participation (MD 0.40, 95% CI 0.13 to 0.67, N = 65, 1 study) in the short-term.There is no difference between resistance training and aerobic exercise in terms of the effect on gross motor function in the short term (SMD 0.02, 95% CI -0.50 to 0.55, N = 56, 2 studies, low-quality evidence).Thirteen trials did not report adverse events, seven reported no adverse events, and nine reported non-serious adverse events. AUTHORS' CONCLUSIONS: The quality of evidence for all conclusions is low to very low. As included trials have small sample sizes, heterogeneity may be underestimated, resulting in considerable uncertainty relating to effect estimates. For children with CP, there is evidence that aerobic exercise may result in a small improvement in gross motor function, though it does not improve gait speed. There is evidence that resistance training does not improve gait speed, gross motor function, participation or quality of life among children with CP.Based on the evidence available, exercise appears to be safe for people with CP; only 55% of trials, however, reported adverse events or stated that they monitored adverse events. There is a need for large, high-quality, well-reported RCTs that assess the effectiveness of exercise in terms of activity and participation, before drawing any firm conclusions on the effectiveness of exercise for people with CP. Research is also required to determine if current exercise guidelines for the general population are effective and feasible for people with CP.

Acute alcoholic hepatitis and cellular Th1 immune responses to alcohol dehydrogenase.

BACKGROUND: Alcoholic hepatitis is characterised by florid hepatic inflammation, liver failure, and death within 28 days in 35% of patients. We recently showed proliferative peripheral blood mononuclear cell (PBMC) responses to alcohol dehydrogenase (ADH) in patients with alcohol-related cirrhosis, associated with T-helper-type 1 (Th1) immunity and disease severity. We aimed to define whether ADH-specific cellular immunity is present in alcoholic hepatitis. METHODS: PBMCs were collected from 15 patients with alcoholic hepatitis (modified Maddrey's discriminant function >32), nine with alcohol-related cirrhosis (long-term alcohol abstinence), and three healthy controls. 25 overlapping peptides, spanning the human ADH ß1 subunit, were constructed. Proliferation to ADH peptides (1 × 10(5) cells per well, cultured with 10 mM peptides for 7 days) was assessed by (3)H-thymidine incorporation. A stimulation index (SI) of 2·5 or more was regarded as positive. ELISA measured concentrations of interferon γ (IFNγ), interleukin (IL) 17, and IL4 from supernatant. FINDINGS: PBMCs from seven of 15 patients with alcoholic hepatitis recognised one to three ADH peptides (SI ≤5·7). IFNγ (mean 390·9 pg/mL [SE 31·4]) was detected in 48% of wells, IL17 (20·1 [3 ·4]) in 15%, and IL4 (90·5 [9·3]) in 14%. PBMCs from six of the nine patients with alcohol-related cirrhosis recognised one to five peptides (SI ≤5·2). IFNγ (360·7 [58·9], p>0·05) was detected in 31% of wells, IL17 (57·7 [10·9], p=0·0006) in 19%, and IL4 (219·7 [11·2], p=0·0012) in 28%. PBMCs from two healthy controls recognised one to two peptides (SI ≤3·1); all cytokine levels were below baseline. INTERPRETATION: Proliferative anti-ADH immune responses in alcoholic hepatitis focused on individual epitopic regions. Predominance of proinflammatory Th1 responses was more pronounced in alcoholic hepatitis than in alcoholic-related cirrhosis. This finding requires investigation of targeted therapies to inhibit Th1 immunity in alcoholic hepatitis. FUNDING: Wellcome Trust.

Blockade of PD1 and TIM3 restores innate and adaptive immunity in patients with acute alcoholic hepatitis.

BACKGROUND & AIMS: Susceptibility to bacterial infection is a feature of alcohol-related liver disease. Programmed cell death 1 (PD1), the T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3, also known as hepatitis A virus cellular receptor 2), and their respective ligands-CD274 (also known as PD ligand 1 [PDL1]) and galectin-9-are inhibitory receptors that regulate the balance between protective immunity and host immune-mediated damage. However, their sustained hyperexpression promotes immune exhaustion and paralysis. We investigated the role of these immune inhibitory receptors in driving immune impairments in patients with alcoholic liver disease. METHODS: In a prospective study, we collected blood samples from 20 patients with acute alcoholic hepatitis (AAH), 16 patients with stable advanced alcohol-related cirrhosis, and 12 healthy individuals (controls). Whole blood or peripheral blood mononuclear cells were assessed for expression of PD1, PDL1, TIM3, galectin-9, and Toll-like receptors on subsets of innate and adaptive immune effector cells. We measured antibacterial immune responses to lipopolysaccharide (endotoxin) using ELISpot assays, and used flow cytometry to quantify cytokine production, phagocytosis, and oxidative burst in the presence or absence of blocking antibodies against PD1 or TIM3. RESULTS: Antibacterial innate and adaptive immune responses were greatly reduced in patients with AAH, compared with controls, and patients with alcohol-related cirrhosis had less severe dysfunctions in innate immune effector cells and preserved functional T-cell responses. Fewer T cells from patients with AAH produced interferon gamma in response to lipopolysaccharide, compared with controls. In addition, patients with AAH had greater numbers of interleukin 10-producing T cells, and reduced levels of neutrophil phagocytosis and oxidative burst in response to Escherichia coli stimulation, compared with controls. T cells from patients with AAH, but not alcohol-related cirrhosis, expressed higher levels of PD1 and PDL1, or TIM3 and galectin-9, than T cells from controls. Antibodies against PD1 and TIM3 restored T-cell production of interferon gamma, reduced the numbers of interleukin 10-producing T cells, and increased neutrophil antimicrobial activities. Circulating levels of endotoxin in plasma from patients with AAH caused over expression of immune inhibitory receptors on T cells via Toll-like receptor 4 binding to CD14(+) monocytes. CONCLUSIONS: Antibacterial immune responses are impaired in patients with AAH. Lymphocytes from these patients express high levels of immune inhibitory receptors, produce lower levels of interferon gamma, and have increased IL10 production due to chronic endotoxin exposure. These effects can be reversed by blocking PD1 and TIM3, which increase the antimicrobial activities of T cells and neutrophils.