Early positive approaches to support (E-PAtS): Qualitative experiences of a new support programme for family caregivers of young children with intellectual and developmental disabilities.

BACKGROUND: Early Positive Approaches to Support (E-PAtS) is a co-produced and co-facilitated group programme that aims to provide early years support to family caregivers of children with Intellectual and Developmental Disabilities. METHOD: Thirty-five caregivers who had attended E-PAtS groups took part in individual interviews or focus groups. Caregiver experiences concerning attendance of E-PAtS were explored, in relation to process variables and perceived outcomes. Interviews were thematically analysed. RESULTS: Three major themes were identified: our group, evolving emotions, and positive approaches. Being with and being supported by other families was very important to caregivers. Families reported increased confidence and greater realisation of the need for self-care. Children were reported to show fewer behaviours that challenge and increases in adaptive skills. Findings corresponded to mechanisms and outcomes in the E-PAtS logic model. CONCLUSION: E-PAtS shows promise as one way families and children with Intellectual and Developmental Disabilities can access early years support.

Factors associated with short versus prolonged tracheostomy length of cannulation and the relationship between length of cannulation and adverse events.

BACKGROUND: Tracheostomy management and care is multifaceted and costly, commonly involving complex patients with prolonged hospitalisation. Currently, there are no agreed definitions of short and prolonged length of tracheostomy cannulation (LOC) and no consensus regarding the key factors that may be associated with time to decannulation. OBJECTIVES: The aims of this study were to identify the factors associated with short and prolonged LOC and to examine the number of tracheostomy-related adverse events of patients who had short LOC versus prolonged LOC. METHODS: A retrospective observational study was undertaken at a large metropolitan tertiary hospital. Factors known at the time of tracheostomy insertion, including patient, acuity, medical, airway, and tracheostomy factors, were analysed using Cox proportional hazards model and Kaplan-Meier survival curves, with statistically significant factors then analysed using univariate logistic regression to determine a relationship to short or prolonged LOC as defined by the lowest and highest quartiles of the study cohort. The number of tracheostomy-related adverse events was analysed using the Kaplan-Meier survival curve. RESULTS: One hundred twenty patients met the inclusion criteria. Patients who had their tracheostomy performed for loss of upper airway were associated with short LOC (odds ratio [OR]: 2.30 (95% confidence interval [CI]: 1.01-5.25) p = 0.049). Three factors were associated with prolonged LOC: an abdominal/gastrointestinal tract diagnosis (OR: 5.00 [95% CI: 1.40-17.87] p = 0.013), major surgery (OR: 2.51 [95% CI: 1.05-6.01] p = 0.038), and intubation for >12 days (OR: 0.30 [95% CI: 0.09-0.97] p = 0.044). Patients who had one or ≥2 tracheostomy-related adverse events had a high likelihood of prolonged LOC (OR: 5.21 [95% CI: 1.95-13.94] p = ≤0.001 and OR: 12.17 [95% CI: 2.68-55.32] p ≤ 0.001, respectively). CONCLUSION: Some factors that are known at the time of tracheostomy insertion are associated with duration of tracheostomy cannulation. Tracheostomy-related adverse events are related to a high risk of prolonged LOC.

Global Tracheostomy Collaborative: data-driven improvements in patient safety through multidisciplinary teamwork, standardisation, education, and patient partnership.

There is growing recognition of the need for a coordinated, systematic approach to caring for patients with a tracheostomy. Tracheostomy-related adverse events remain a pervasive global problem, accounting for half of all airway-related deaths and hypoxic brain damage in critical care units. The Global Tracheostomy Collaborative (GTC) was formed in 2012 to improve patient safety and quality of care, emphasising knowledge, skills, teamwork, and patient-centred approaches. Inspired by quality improvement leads in Australia, the UK, and the USA, the GTC implements and disseminates best practices across hospitals and healthcare trusts. Its database collects patient-level information on quality, safety, and organisational efficiencies. The GTC provides an organising structure for quality improvement efforts, promoting safety of paediatric and adult patients. Successful implementation requires instituting key drivers for change that include effective training for health professionals; multidisciplinary team collaboration; engagement and involvement of patients, their families, and carers; and data collection that allows tracking of outcomes. We report the history of the collaborative, its database infrastructure and analytics, and patient outcomes from more than 6500 patients globally. We characterise this patient population for the first time at such scale, reporting predictors of adverse events, mortality, and length of stay indexed to patient characteristics, co-morbidities, risk factors, and context. In one example, the database allowed identification of a previously unrecognised association between bleeding and mortality, reflecting ability to uncover latent risks and promote safety. The GTC provides the foundation for future risk-adjusted benchmarking and a learning community that drives ongoing quality improvement efforts worldwide.

It's hard to talk about breathlessness: a unique insight from respiratory trainees .

This paper describes how difficult it can be to discuss the experience of breathlessness with patients, as identified by respiratory trainees in a psychology-led workshop. The reasons why it is considered an essential role for clinicians to facilitate conversations about patients' breathlessness are outlined within the context of the challenges of respiratory care. The benefits for both patient and clinician are described including rapport building, more focused and targeted consultations, and increasing a patient's receptivity to interventions. The value of preparing a patient to actively engage with their breathlessness management is highlighted. As a way to support clinicians to initiate talk about breathlessness, a 'five-step guide to talking' is presented.

People with dementia as peer workers, challenges, and benefits: a thematic analysis and nominal groups study.

BACKGROUND: There are national initiatives to involve service users in service delivery. However, programs employing people with dementia as peer support workers (PSWs) in memory services are in their infancy. This study is the first to explore the challenges and benefits to staff and peers involved in such a program. METHODS: Focus groups, structured based on nominal groups (NG) methodology were run with PSWs and clinical staff from two memory services. In total, there were 12 participants, with three focus groups: PSWs alone (n = 3); staff members alone (n = 6); and PSWs and staff members combined (n = 6). Data were analyzed through thematic analysis of recorded session content and the ranking of themes inherent in an NG approach. RESULTS: Perceived benefits of the PSW program were similar for staff and PSWs and included personal benefits for PSWS and stereotype reduction for staff. More challenges were reported by staff than PSWs, but both groups agreed that role definition and dealing with the cognitive deterioration inherent in dementia were key issues. CONCLUSIONS: The PSW program does have benefits for involved staff and PSWs. However, the challenges identified highlight the need for careful and consensual setup and consideration of power dynamics, with agreed roles and clear guidelines to deal with cognitive deterioration.

Limited validity of the Hospital Anxiety and Depression Scale (HADS) in dementia: evidence from a confirmatory factor analysis.

OBJECTIVES: The Hospital Anxiety and Depression Scale (HADS) is a well-validated, self-report measure of both anxiety and depression. It is frequently used with people with dementia. However, its structural validity has never been examined in this population. The current study used confirmatory factor analysis (CFA) to assess this. METHODS: Baseline data from two intervention studies for people with mild to moderate dementia were combined (N = 268). CFA was used to test whether a one, two or three factor structure best fit the data. Indices of model misspecification were examined to test for poor quality items, and models re-specified accordingly. Finally, measurement invariance across gender and different levels of cognitive impairment was assessed. RESULTS: A one-factor structure did not fit the data. Two and three factor structures fitted the data equally well. Model fit was improved by removal of two items. Measurement invariance was adequate across gender, but poor across groups with differing levels of cognitive impairment. CONCLUSION: The HADS is acceptable and feasible but difficult to interpret in a dementia population. We suggest that it should be interpreted as measuring two separate factors of anxiety and depression and not one 'distress' factor. However, two items may need to be removed, affecting cut-off scores. Poor measurement invariance means the HADS may not be a good tool for measuring differences in anxiety and depression between those with mild and those with moderate cognitive impairment. Copyright © 2016 John Wiley & Sons, Ltd.

One-carbon metabolism in neurodevelopmental disorders: using broad-based nutraceutics to treat cognitive deficits in complex spectrum disorders.

Folate and choline, two nutrients involved in the one-carbon metabolic cycle, are intimately involved in regulating DNA integrity, synthesis, biogenic amine synthesis, and methylation. In this review, we discuss evidence that folate and choline play an important role in normal cognitive development, and that altered levels of these nutrients during periods of high neuronal proliferation and synaptogenesis can result in diminished cognitive function. We also discuss the use of these nutrients as therapeutic agents in a spectrum of developmental disorders in which intellectual disability is a prominent feature, such as in Fragile-X, Rett syndrome, Down syndrome, and Autism spectrum disorders. A survey of recent literature suggests that nutritional supplements have mild, but generally consistent, effects on improving cognition. Intervening with supplements earlier rather than later during development is more effective in improving cognitive outcomes. Given the mild improvements seen after treatments using nutrients alone, and the importance of the genetic profile of parents and offspring, we suggest that using nutraceutics early in development and in combination with other therapeutics are likely to have positive impacts on cognitive outcomes in a broad spectrum of complex neurodevelopmental disorders.

Acetyl-L-carnitine improves behavior and dendritic morphology in a mouse model of Rett syndrome.

Rett syndrome (RTT) is a devastating neurodevelopmental disorder affecting 1 in 10,000 girls. Approximately 90% of cases are caused by spontaneous mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2). Girls with RTT suffer from severe motor, respiratory, cognitive and social abnormalities attributed to early deficits in synaptic connectivity which manifest in the adult as a myriad of physiological and anatomical abnormalities including, but not limited to, dimished dendritic complexity. Supplementation with acetyl-L-carnitine (ALC), an acetyl group donor, ameliorates motor and cognitive deficits in other disease models through a variety of mechanisms including altering patterns of histone acetylation resulting in changes in gene expression, and stimulating biosynthetic pathways such as acetylcholine. We hypothesized ALC treatment during critical periods in cortical development would promote normal synaptic maturation, and continuing treatment would improve behavioral deficits in the Mecp2(1lox) mouse model of RTT. In this study, wildtype and Mecp2(1lox) mutant mice received daily injections of ALC from birth until death (postnatal day 47). General health, motor, respiratory, and cognitive functions were assessed at several time points during symptom progression. ALC improved weight gain, grip strength, activity levels, prevented metabolic abnormalities and modestly improved cognitive function in Mecp2 null mice early in the course of treatment, but did not significantly improve motor or cognitive functions assessed later in life. ALC treatment from birth was associated with an almost complete rescue of hippocampal dendritic morphology abnormalities with no discernable side effects in the mutant mice. Therefore, ALC appears to be a promising therapeutic approach to treating early RTT symptoms and may be useful in combination with other therapies.

Preclinical research in Rett syndrome: setting the foundation for translational success.

In September of 2011, the National Institute of Neurological Disorders and Stroke (NINDS), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the International Rett Syndrome Foundation (IRSF) and the Rett Syndrome Research Trust (RSRT) convened a workshop involving a broad cross-section of basic scientists, clinicians and representatives from the National Institutes of Health (NIH), the US Food and Drug Administration (FDA), the pharmaceutical industry and private foundations to assess the state of the art in animal studies of Rett syndrome (RTT). The aim of the workshop was to identify crucial knowledge gaps and to suggest scientific priorities and best practices for the use of animal models in preclinical evaluation of potential new RTT therapeutics. This review summarizes outcomes from the workshop and extensive follow-up discussions among participants, and includes: (1) a comprehensive summary of the physiological and behavioral phenotypes of RTT mouse models to date, and areas in which further phenotypic analyses are required to enhance the utility of these models for translational studies; (2) discussion of the impact of genetic differences among mouse models, and methodological differences among laboratories, on the expression and analysis, respectively, of phenotypic traits; and (3) definitions of the standards that the community of RTT researchers can implement for rigorous preclinical study design and transparent reporting to ensure that decisions to initiate costly clinical trials are grounded in reliable preclinical data.

Gene-environment interactions and epigenetic pathways in autism: the importance of one-carbon metabolism.

Both genetic and epigenetic factors play important roles in the rate and severity of classic autism and autism spectrum disorders (ASDs). This review focuses on DNA methylation as a key epigenetic mechanism in autism. The critical role that one-carbon (C1) metabolism plays in establishing and maintaining DNA methylation patterns makes it a likely candidate pathway to regulate epigenetic processes in ASDs. This review is the first, to our knowledge, to examine how altering C1 metabolic function through genetic and environmental factors (focusing on diet) may lead to aberrant DNA methylation and increase susceptibility to ASDs. Additionally, the critical time windows for sensitivity to genetic and dietary factors both during the development of cortical networks implicated in ASDs and in regard to potential treatments are discussed. One thing is clear, if C1 metabolism plays a critical role in ASDs, it provides a potential avenue for treatment and perhaps, ultimately, prevention.

Glutamate carboxypeptidase II and folate deficiencies result in reciprocal protection against cognitive and social deficits in mice: implications for neurodevelopmental disorders.

Interactions between genetic and environmental risk factors underlie a number of neuropsychiatric disorders, including schizophrenia (SZ) and autism (AD). Due to the complexity and multitude of the genetic and environmental factors attributed to these disorders, recent research strategies focus on elucidating the common molecular pathways through which these multiple risk factors may function. In this study, we examine the combined effects of a haplo-insufficiency of glutamate carboxypeptidase II (GCPII) and dietary folic acid deficiency. In addition to serving as a neuropeptidase, GCPII catalyzes the absorption of folate. GCPII and folate depletion interact within the one-carbon metabolic pathway and/or of modulate the glutamatergic system. Four groups of mice were tested: wild-type, GCPII hypomorphs, and wild-types and GCPII hypomorphs both fed a folate deficient diet. Due to sex differences in the prevalence of SZ and AD, both male and female mice were assessed on a number of behavioral tasks including locomotor activity, rotorod, social interaction, prepulse inhibition, and spatial memory. Wild-type mice of both sexes fed a folic acid deficient diet showed motor coordination impairments and cognitive deficits, while social interactions were decreased only in males. GCPII mutant mice of both sexes also exhibited reduced social propensities. In contrast, all folate-depleted GCPII hypomorphs performed similarly to untreated wild-type mice, suggesting that reduced GCPII expression and folate deficiency are mutually protective. Analyses of folate and neurometabolite levels associated with glutamatergic function suggest several potential mechanisms through which GCPII and folate may be interacting to create this protective effect.

Cognitive deficits in Rett syndrome: what we know and what we need to know to treat them.

Rett syndrome is an autism spectrum disorder and a leading cause of severe mental retardation in girls. The nature of the cognitive abnormalities in Rett, as described in humans and other animal models, and its potential reversibility and treatment are the subject of this review. Rett syndrome is associated with severe mental retardation and a host of impairments that include social and motor deficits, and respiratory and bone abnormalities. More than 80% of Rett girls have mutations in the gene that encodes MeCP2, which is a protein with a complex set of functions that include transcriptional repression and activation. The complex phenotype associated with Rett and the knowledge of the causal genetic mutation provide a unique opportunity within the autism spectrum to explore the relationship between transcriptional control, brain abnormalities and specific behavioral functions, importantly the elusive cognitive dysfunctions associated with mental retardation. The nature of the cognitive abnormalities related to Rett and the potential reversibility and treatment of these abnormalities have not been studied as extensively as some of the other aspects of the Rett phenotype. The cognitive phenotype associated with Rett is also less well studied relative to that in other well known developmental disorders, such as Down syndrome and Fragile X. Nevertheless, some recent studies provide hope that the cognitive impairments, as well as other symptoms of Rett, can be rescued.

Cognitive and social functions and growth factors in a mouse model of Rett syndrome.

Rett syndrome (RTT) is an autism-spectrum disorder caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2). Abnormalities in social behavior, stereotyped movements, and restricted interests are common features in both RTT and classic autism. While mouse models of both RTT and autism exist, social behaviors have not been explored extensively in mouse models of RTT. Here, we report cognitive and social abnormalities in Mecp2(1lox) null mice, an animal model of RTT. The null mice show severe deficits in short- and long-term object recognition memories, reminiscent of the severe cognitive deficits seen in RTT girls. Social behavior, however, is abnormal in that the null mice spend more time in contact with stranger mice than do wildtype controls. These findings are consistent with reports of increased reciprocal social interaction in RTT girls relative to classic autism. We also report here that the levels of the neurotrophins brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and nerve growth factor (NGF) are decreased in the hippocampus of the null mice, and discuss how this may provide an underlying mechanism for both the cognitive deficits and the increased motivation for social contact observed in the Mecp2(1lox) null mice. These studies support a differential etiology between RTT and autism, particularly with respect to sociability deficits.

Outcomes of dysphagia intervention in a pulmonary rehabilitation program.

People with chronic obstructive pulmonary disease (COPD) or chronic respiratory disease demonstrate an increased prevalence of oropharyngeal dysphagia as a consequence of impaired coordination between respiration and swallowing function. To date, the effect of patient education and intervention on the management of oropharyngeal dysphagia within pulmonary rehabilitation programs has not been reported or evaluated. Data were collected on participants who were enrolled in the Outpatient Pulmonary Rehabilitation Program and who received dysphagia intervention. Intervention consisted of some or all of the following: (1) a 1-hour dysphagia education program, (2) screening for oropharyngeal dysphagia, and (3) individual comprehensive oropharyngeal dysphagia assessment and management if a screening assessment was failed. A statistically significant improvement was found in participants' knowledge of dysphagia and COPD (P < 0.001). Participants' retention of this knowledge 4 days post education remained statistically significant (P < 0.001). Twenty-seven percent of participants who were screened had symptoms of oropharyngeal dysphagia. Fifty-five (53%) participants receiving further individual dysphagia assessment/management correctly completed pre/post swallowing-related quality-of-life surveys (SWAL-QOL). Statistically significant improvement was found in the following subscales: Burden of Dysphagia (P < 0.009), Physical Problems of Dysphagia (P < 0.012) and Managing Diet Options/Food Selection (P < 0.016). Dysphagia education, screening, and management in a pulmonary rehabilitation program improved participants' swallowing-related quality of life and overall self-management of chronic respiratory disease and dysphagia.

Phenotypic characterization of mice heterozygous for a null mutation of glutamate carboxypeptidase II.

Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. Disturbed glutamate signaling resulting in hypofunction of N-methyl-D-aspartate receptors (NMDAR) has been implicated in the pathophysiology of schizophrenia. Glutamate Carboxypeptidase II (GCP II) hydrolyzes N-acetyl-alpha L-aspartyl-L-glutamate (NAAG) into glutamate and N-acetyl-aspartate. NAAG is a neuropeptide that is an NMDAR antagonist as well as an agonist for the metabotropic glutamate receptor-3 (mGluR3), which inhibits glutamate release. The aggregate effect of NAAG is thus to attenuate NMDAR activation. To manipulate the expression of GCP II, LoxP sites were inserted flanking exons 1 and 2, which were excised by crossing with a Cre-expressing mouse. The mice heterozygous for this deletion showed a 50% reduction in the expression level of protein and functional activity of GCP II in brain samples. Heterozygous mutant crosses did not yield any homozygous null animals at birth or as embryos (N > 200 live births and fetuses). These data are consistent with the previous report that GCP II homozygous mutant mice generated by removing exons 9 and 10 of GCP II gene were embryonically lethal and confirm our hypothesis that GCP II plays an essential role early in embryonic development. Heterozygous mice, however, developed normally to adulthood and exhibited increased locomotor activity, reduced social interaction, and a subtle cognitive deficit in working memory.

Outcomes of patients with spinal cord injury before and after introduction of an interdisciplinary tracheostomy team.

OBJECTIVES: To assess outcomes in patients with spinal cord injury (SCI) and a tracheostomy tube (TT), before and after the introduction of a tracheostomy review and management service (TRAMS) for ward-based patients. DESIGN: Matched-pairs design with two cohorts, before and after the intervention. SETTING: 900-bed tertiary hospital in Melbourne, Victoria. PARTICIPANTS: SCI patients with a TT that was removed: 34 patients in the post-TRAMS period (September 2003 to September 2006) were matched to 34 from the pre-TRAMS period (September 1999 to December 2001). INTERVENTION: TRAMS was introduced as a consultative team of specialist physicians, clinical nurse consultants, physiotherapists and speech pathologists. The team coordinated tracheostomy care, conducted twice-weekly rounds, and provided policy, education, and support. MAIN OUTCOME MEASURES: Comparison of length of stay (LOS), duration of cannulation (DOC), improved communication through use of a one-way valve, number of adverse events and related costs. RESULTS: Median patient LOS decreased from 60 days (interquartile range [IQR], 38-106) to 41.5 days (IQR, 29- 62) (P = 0.03). The pre-TRAMS median DOC decreased from 22.5 days (IQR, 17-58) to 16.5 days (IQR, 12-25) (P = 0.08). Speaking-valve use increased from 35% (12/34) to 82% (28/34) (P < 0.01). Median time to a valve trial decreased from 22 days (IQR, 13-44) to 6 days (IQR, 4-10) after TT insertion (P < 0.01). There were two tracheostomy-related medical emergency calls pre-TRAMS and none post-TRAMS. There were no tracheostomy-related deaths in either group. The annual cost savings from implementing TRAMS were about eight times greater than the cost of service provision. CONCLUSION: Implementing a tracheostomy review and management service improved outcomes for SCI patients: they left acute care sooner, spoke sooner, and the TT was removed earlier, with associated cost savings.

Efficacy of a murine-p75-saporin immunotoxin for selective lesions of basal forebrain cholinergic neurons in mice.

Selective lesioning of cholinergic neurons in the basal forebrain provides a tool for examining the functional significance of cholinergic loss, which is associated with a number of developmental and neurodegenerative disorders. A new version of an immunotoxin (murine-p75NTR-saporin) was used to produce a selective loss of cholinergic neurons in the adult basal forebrain of the mouse. This new version of the toxin is significantly more potent and selective than a previously developed version. C57Bl/6J mice (n=30) were given 1 microL of either saline or murine-p75NTR-saporin (0.65 microg/microL or 1.3 microg/microL) into the lateral ventricles, and then sacrificed 10-12 days post-surgery for histological analysis. In contrast to results from the previous version of the toxin, survival of the toxin-treated mice was 100% at both doses. A complete loss of cholinergic neurons was seen in the medial septum (MS) with both doses, while a dose-dependent loss of cholinergic neurons was observed in the nucleus basalis magnocellularis (nBM). The lesions were associated with locomotor hypoactivity and anxiolytic-type behavioral effects. These studies describe the efficacy and selectivity of this new version of murine-p75NTR-saporin, which may be used to provide insight into functional deficits that result from the loss of cholinergic neurons in the mouse basal forebrain.