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1.
Issues Ment Health Nurs ; 44(10): 960-973, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37643312

ABSTRACT

Implementing sensory approaches in psychiatric units has proven challenging. This multi-staged study involved qualitative interviews (n = 7) with mental health care staff in an acute psychiatric ward to identify the local factors influencing use of sensory approaches, and co-design implementation strategies with key stakeholders to improve their use. Using framework analysis, results revealed that the use of sensory approaches were hindered by: inadequate access to sensory resources/equipment; lack of time; lack of staff knowledge; and belief that sensory approaches are not effective or part of staff's role. To address identified barriers a systematic theory-informed method was used to co-design implementation strategies to improve the use of sensory approaches.

2.
Aust Occup Ther J ; 70(5): 599-616, 2023 10.
Article in English | MEDLINE | ID: mdl-37259982

ABSTRACT

BACKGROUND/AIM: Although sensory approaches are recommended to relieve distress and agitation and reduce the use of seclusion and restraint, many Australian psychiatric units have struggled to sustain their practice. The aim of this study was to investigate the barriers and enablers influencing the use of different sensory approaches across one health region in Australia and to obtain recommendations for strategies to improve their use. METHOD: This cross-sectional survey was informed by the Theoretical Domain Framework. Likert scale questions considered barriers and enablers to the use of non-weighted sensory interventions, weighted modalities, sensory rooms, and sensory assessments/plans. Open-ended questions explored participant concerns and recommendations to improve the use of sensory approaches. RESULTS: Participants (n = 211) were from nursing, allied health, medical, and peer support staff across inpatient psychiatric units. Factors most frequently identified as enablers for using sensory approaches were beliefs of positive benefits to consumers (e.g. decreasing distress and agitation); belief it was within the staff's role; and knowledge of the approaches. Limited time was the most common identified barrier. Factors statistically associated with more frequent use were knowledge, skills, confidence, availability, and easy access to sensory tools/equipment. Only 30% of participants were concerned about potential risks of sensory approaches, with this risk mitigated through adequate supervision and thorough risk assessment. Recommendations to improve practice included improved access to, and maintenance of, equipment, more training, and increased staffing. CONCLUSION: This study revealed how barriers and enablers vary for different sensory approaches and how these factors impact their frequency of use in psychiatric units. It provides insights into staff recommendations to improve the use of sensory approaches in one health region in Australia. This knowledge will lead to the development of implementation strategies to address identified barriers and improve the use of sensory approaches in psychiatric units.


Subject(s)
Mental Health , Occupational Therapy , Humans , Australia , Cross-Sectional Studies , Surveys and Questionnaires
3.
Crit Care Med ; 51(7): 936-947, 2023 07 01.
Article in English | MEDLINE | ID: mdl-37058348

ABSTRACT

OBJECTIVES: To evaluate implementation of a video laryngoscope (VL) as a coaching device to reduce adverse tracheal intubation associated events (TIAEs). DESIGN: Prospective multicenter interventional quality improvement study. SETTING: Ten PICUs in North America. PATIENTS: Patients undergoing tracheal intubation in the PICU. INTERVENTIONS: VLs were implemented as coaching devices with standardized coaching language between 2016 and 2020. Laryngoscopists were encouraged to perform direct laryngoscopy with video images only available in real-time for experienced supervising clinician-coaches. MEASUREMENTS AND MAIN RESULTS: The primary outcome was TIAEs. Secondary outcomes included severe TIAEs, severe hypoxemia (oxygen saturation < 80%), and first attempt success. Of 5,060 tracheal intubations, a VL was used in 3,580 (71%). VL use increased from baseline (29.7%) to implementation phase (89.4%; p < 0.001). VL use was associated with lower TIAEs (VL 336/3,580 [9.4%] vs standard laryngoscope [SL] 215/1,480 [14.5%]; absolute difference, 5.1%; 95% CI, 3.1-7.2%; p < 0.001). VL use was associated with lower severe TIAE rate (VL 3.9% vs SL 5.3%; p = 0.024), but not associated with a reduction in severe hypoxemia (VL 15.7% vs SL 16.4%; p = 0.58). VL use was associated with higher first attempt success (VL 71.8% vs SL 66.6%; p < 0.001). In the primary analysis after adjusting for site clustering, VL use was associated with lower adverse TIAEs (odds ratio [OR], 0.61; 95% CI, 0.46-0.81; p = 0.001). In secondary analyses, VL use was not significantly associated with severe TIAEs (OR, 0.72; 95% CI, 0.44-1.19; p = 0.20), severe hypoxemia (OR, 0.95; 95% CI, 0.73-1.25; p = 0.734), or first attempt success (OR, 1.28; 95% CI, 0.98-1.67; p = 0.073). After further controlling for patient and provider characteristics, VL use was independently associated with a lower TIAE rate (adjusted OR, 0.65; 95% CI, 0.49-0.86; p = 0.003). CONCLUSIONS: Implementation of VL-assisted coaching achieved a high level of adherence across the PICUs. VL use was associated with reduced adverse TIAEs.


Subject(s)
Laryngoscopes , Mentoring , Humans , Child , Prospective Studies , Intubation, Intratracheal/methods , Laryngoscopy , Intensive Care Units, Pediatric , Hypoxia/prevention & control , Hypoxia/etiology
4.
Aust Occup Ther J ; 69(5): 559-573, 2022 10.
Article in English | MEDLINE | ID: mdl-35706333

ABSTRACT

BACKGROUND/AIM: Australian guidelines and policies recommend the use of sensory approaches in mental health care. Nevertheless, many Australian psychiatric units report difficulty sustaining these approaches. To inform efforts to close the gap between recommendations and practice, the aim of this study was to understand the patterns of use of sensory approaches and what demographic and clinical factors influence their use, across one health region in Queensland, Australia. METHODS: Using a cross-sectional survey design, a custom-designed questionnaire was distributed via email and in paper form to health professionals and peer support workers working in acute, secure, and community care psychiatric units across one health region. Information on demographics and the use of various sensory interventions was gathered utilising both open-ended and Likert scale questions. RESULTS: Useable questionnaires were collected from 183 participants from various disciplines (77% nursing). The majority reported using sensory approaches with a limited number of consumers, and almost 9% never used the approach. Activity-based sensory interventions and sensory equipment were most often used, whereas sensory assessments, sensory plans, and sensory groups were least used. Sensory interventions were mainly used to reduce consumer anxiety and agitation and to assist with emotional regulation. Factors positively correlated with frequency of use for all interventions were discipline (occupational therapy); working in an acute inpatient unit; and training in sensory approaches. Age was negatively correlated with frequency of use only for weighted modalities. CONCLUSIONS: This study revealed that sensory approaches were used by most staff though with a limited proportion of consumers in psychiatric units in one large metropolitan health service. It provides insights into the factors influencing frequency of use, highlighting the importance of training in sensory approaches and access to occupational therapists. With this knowledge, we can work towards closing the gap between recommendations and the practice of sensory approaches.


Subject(s)
Occupational Therapy , One Health , Australia , Cross-Sectional Studies , Humans , Inpatients , Surveys and Questionnaires
5.
Cureus ; 12(6): e8594, 2020 Jun 13.
Article in English | MEDLINE | ID: mdl-32676235

ABSTRACT

Hypophosphatasia (HPP) is a rare inherited bone disorder identified by impaired bone mineralization. There are seven subtypes of HPP mainly characterized by their age of onset. These subtypes consist of perinatal (prenatal) benign, perinatal lethal, infantile, childhood, adult, odontohypophosphatasia, and pseudohypophosphatasia. Due to limited awareness of the condition, either misdiagnosis or delayed diagnosis is common. Furthermore, the condition is frequently treated with contraindicated drugs. This literature illustrates the most recent findings on the etiology, pathophysiology, clinical manifestations, diagnosing, and treatment for HPP and its subtypes. The etiology of the disease consists of loss-of-function mutations of the ALPL gene on chromosome one, which encodes for tissue nonspecific isoenzyme of alkaline phosphatase (TNAP). A decrease of TNAP reduces inorganic phosphate (Pi) for bone mineralization and allows for an increase in inorganic pyrophosphate (PPi) and phosphorylated osteopontin (p-OPN), which further reduces bone mineralization. The combination of these processes softens bone and mediates a clinical presentation similar to rickets/osteomalacia. HPP has an additional wide range of clinical features depending on its subtype. Although a concrete diagnostic guideline has not yet been established, many studies have supported a similar method of identifying HPP. Clinical features, radiological findings, and/or biomarker levels of the disorder should raise suspicion and encourage the inclusion of HPP as a differential diagnosis. Biomarkers, especially alkaline phosphatase (ALP), are major contributors to diagnosis. However, genetic testing is done for definitive diagnosis. The primary treatment for HPP is the reintroduction of TNAP as a recombinant enzyme called asfotase alfa. There are additional pharmaceutical treatments and in some cases, surgical intervention may be indicated. Pharmaceutical therapies such as bisphosphonates, denosumab, potent antiresorptive agents, and vitamin D are contraindicated in adults with HPP. We hope to raise awareness for HPP in order to prevent delayed diagnosis or misdiagnosis. We plan to encourage appropriate care and avoid treatments that may be contraindicating. We also encourage the development of a diagnostic guideline that will promote a consistently favorable patient prognosis.

6.
Ann Diagn Pathol ; 47: 151545, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32505971

ABSTRACT

Malignant atrophic papulosis (Degos disease) is an unusual thrombotic microangiopathy of uncertain etiology. The disease characteristically involves the skin and internal organs, with nervous system involvement more common in children. We present a case with diverse neurological manifestations including cranial nerve palsies, gait instability, and urinary incontinence. The patient also developed white papular lesions on her lower extremities and back. Magnetic resonance imaging (MRI) demonstrated progressive intracranial and spinal abnormalities. Despite treatment with numerous biologic agents, the patient had persistent clinical deterioration and expired one month after admission. We highlight the extensive neurologic manifestations of Degos disease correlated with neuroradiological imaging and pathological features. Nervous system involvement in Degos disease requires careful neurologic and dermatologic exam with central nervous system (CNS) magnetic resonance imaging to distinguish it from non-organic etiologies of similar symptoms.


Subject(s)
Magnetic Resonance Imaging/methods , Malignant Atrophic Papulosis/diagnostic imaging , Malignant Atrophic Papulosis/pathology , Nervous System Diseases/etiology , Thrombotic Microangiopathies/pathology , Adolescent , Antibodies, Monoclonal, Humanized/therapeutic use , Biological Factors/therapeutic use , Central Nervous System/diagnostic imaging , Central Nervous System/pathology , Cranial Nerve Diseases/diagnosis , Cranial Nerve Diseases/etiology , Disease Progression , Drug Therapy, Combination , Fatal Outcome , Female , Gait Disorders, Neurologic/diagnosis , Gait Disorders, Neurologic/etiology , Humans , Malignant Atrophic Papulosis/complications , Malignant Atrophic Papulosis/drug therapy , Nervous System Diseases/diagnosis , Nitriles , Pyrazoles/therapeutic use , Pyrimidines , Skin/pathology , Thrombotic Microangiopathies/etiology , Urinary Incontinence/diagnosis , Urinary Incontinence/etiology
9.
Science ; 367(6482): 1084, 2020 Mar 06.
Article in English | MEDLINE | ID: mdl-32139535
10.
Int J Ment Health Nurs ; 29(4): 608-621, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32061046

ABSTRACT

Clinical guidelines and policies worldwide call for sensory modulation approaches to be incorporated into inpatient mental health care to assist in eliminating the use of restrictive practices. Although increasing evidence shows that these approaches reduce patient distress and the need for seclusion and restraint, sensory modulation approaches have been challenging to implement in many psychiatric units. Implementation strategies can effectively support inclusion of new approaches by addressing potential barriers to change and supporting likely enabling factors. This study aimed to gain a better understanding of the barriers and enablers influencing implementation of sensory modulation approaches in psychiatric inpatient units in one health region in Australia. A qualitative descriptive study design was used, with three focus groups and a total of 15 participants from nursing and allied health disciplines answering questions about the use of sensory modulation approaches. Framework analysis using the Theoretical Domains Framework and thematic analysis was used to analyse data. Overall, participants were positive about the use of sensory modulation approaches, particularly for reducing distress. Four domains (Social Influences; Belief about Consequences; Professional Role and Identify; and Environmental Context and Resources) were identified as the most salient. The key influencing factors were support from peers; beliefs about risks; belief it was part of their role; and availability of resources and materials. Numerous challenges and opportunities related to implementing sensory modulation approaches in mental health inpatient units, identified in this study, provide insights to support effective implementation of these approaches, underpinning more person-centred, trauma-informed, and recovery-orientated care.


Subject(s)
Inpatients , Mental Health , Australia , Humans , Qualitative Research , Restraint, Physical
11.
Pediatr Crit Care Med ; 19(5): e242-e250, 2018 05.
Article in English | MEDLINE | ID: mdl-29406378

ABSTRACT

OBJECTIVES: As of July 2013, pediatric resident trainee guidelines in the United States no longer require proficiency in nonneonatal tracheal intubation. We hypothesized that laryngoscopy by pediatric residents has decreased over time, with a more pronounced decrease after this guideline change. DESIGN: Prospective cohort study. SETTING: Twenty-five PICUs at various children's hospitals across the United States. PATIENTS: Tracheal intubations performed in PICUs from July 2010 to June 2016 in the multicenter tracheal intubation database (National Emergency Airway Registry for Children). INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Prospective cohort study in which all primary tracheal intubations occurring in the United States from July 2010 to June 2016 in the multicenter tracheal intubation database (National Emergency Airway Registry for Children) were analyzed. Participating PICU leaders were also asked to describe their local airway management training for residents. Resident participation trends over time, stratified by presence of a Pediatric Critical Care Medicine fellowship and airway training curriculum for residents, were described. A total of 9,203 tracheal intubations from 25 PICUs were reported. Pediatric residents participated in 16% of tracheal intubations as first laryngoscopists: 14% in PICUs with a Pediatric Critical Care Medicine fellowship and 34% in PICUs without one (p < 0.001). Resident participation decreased significantly over time (3.4% per year; p < 0.001). The decrease was significant in ICUs with a Pediatric Critical Care Medicine fellowship (p < 0.001) but not in ICUs without one (p = 0.73). After adjusting for site-level clustering, patient characteristics, and Pediatric Critical Care Medicine fellowship presence, the Accreditation Council for Graduate Medical Education guideline change was not associated with lower participation by residents (odds ratio, 0.86; 95% CI, 0.59-1.24; p = 0.43). The downward trend of resident participation was similar regardless of the presence of an airway curriculum for residents. CONCLUSION: Laryngoscopy by pediatric residents has substantially decreased over time. This downward trend was not associated with the 2013 Accreditation Council for Graduate Medical Education change in residency requirements.


Subject(s)
Intensive Care Units, Pediatric/trends , Internship and Residency/trends , Intubation, Intratracheal/trends , Laryngoscopy/education , Pediatrics/education , Child , Child, Preschool , Curriculum , Female , Humans , Infant , Infant, Newborn , Intubation, Intratracheal/methods , Laryngoscopy/trends , Male , Pediatrics/trends , Retrospective Studies , United States
12.
J Cogn Psychother ; 32(3): 155-170, 2018 Aug.
Article in English | MEDLINE | ID: mdl-32746432

ABSTRACT

Overweight and obesity are disabling problems for veterans and place a heavy toll on their physical and mental health. Acceptance and commitment therapy (ACT) is an empirically supported intervention that shows promise in improving binge eating, weight, and psychological functioning. This preliminary study evaluated the feasibility and acceptability of an 8-week ACT group intervention for binge eating in veterans (N = 85) who were overweight or obese and explored preliminary intervention effects on binge eating and physical and mental health functioning. Veterans were predominantly male (86.7%) with an average age of 58 years, and 65% endorsed clinically significant binge eating. Qualitative results indicated the majority of veterans found the intervention useful. Baseline to post-treatment comparisons found significant reductions in binge eating symptoms, depression, global psychological distress, and body mass index, as well as improvement in functioning. Findings suggest implementing ACT for binge eating in veterans is feasible and deserves further exploration, addressing binge eating and weight control. Future studies should examine ACT for this population in a randomized controlled trial.

13.
Int J Lang Commun Disord ; 53(3): 480-494, 2018 05.
Article in English | MEDLINE | ID: mdl-29218830

ABSTRACT

BACKGROUND: Children with developmental language disorder (DLD) frequently have difficulties with word learning and understanding vocabulary. For these children, this can significantly impact on social interactions, daily activities and academic progress. Although there is literature providing a rationale for targeting word learning in such children, there is little evidence for the effectiveness of specific interventions in this area for children with identified DLD. AIMS: To establish whether direct one-to-one intervention for children with DLD over 9 years of age leads to improved abilities to identify, comprehend, define, and use nouns and verbs targeted in intervention as compared with non-targeted control items and whether or not the participants' rating of their own knowledge of the words changes with intervention. METHODS & PROCEDURES: Twenty-five children and young people with language disorder (aged 9;4-16;1) participated in the study: 18 with DLD and seven with a language disorder associated with autism spectrum disorder (ASD). Two assessments of different levels were created: a higher ability (less frequent words) and a lower ability (more frequent words). Participants' speech and language therapists (SLTs) decided which level would be the most appropriate for each participant. Four tasks were carried out as part of the assessment and the scores were used to identify which words each participant worked on. Participants received one 30-min session per week one-to-one with their own SLT for 7 weeks, plus a 5-min revision session in between each main session. During each of the first five sessions, participants learned two new words; the two final sessions were spent revising the 10 words which had been targeted. OUTCOMES & RESULTS: Post-intervention assessment showed an increase in scores for both treated and control words. However, progress on treated words was significantly greater than on control words (d = 1.07), indicating effectiveness of intervention. The difference between progress on targeted and control words was found both for nouns (d = 1.29) and verbs (d = 0.64), but the effect size was larger for nouns. Whether or not the participants had an associated ASD did not affect the results. The children's self-rating of their knowledge of the targeted words was also significantly higher than for control words post-intervention. CONCLUSIONS & IMPLICATIONS: The intervention delivered one-to-one by the participants' usual SLT was effective in teaching new vocabulary to older children with language disorders. This shows that older children with language disorders can make progress with direct one-to-one intervention focused on vocabulary.


Subject(s)
Child Language , Language Development Disorders/therapy , Language Therapy/methods , Vocabulary , Adolescent , Autism Spectrum Disorder/psychology , Child , Child, Preschool , Comprehension , Female , Humans , Language Development Disorders/psychology , Language Tests , Learning , Male , Treatment Outcome
14.
Pain ; 159(2): 284-297, 2018 02.
Article in English | MEDLINE | ID: mdl-29194091

ABSTRACT

Phototoxicity-induced pain is a major clinical problem triggered by light acting on photosensitising drugs or endogenous porphyrins, notably protoporphyrin IX (PpIX), an intermediary in heme biosynthesis. Protoporphyrin IX accumulates in individuals with erythropoietic protoporphyria and is elevated during photodynamic therapy subsequent to application of 5-aminolevulinic acid (ALA). Pain occurs during irradiation of PpIX and responds poorly to conventional analgesics. Our objective was to develop a model of PpIX phototoxicity pain and investigate the potential of menthol as an analgesic. Application of ALA to the tails of C57 black and SWISS white mice caused PpIX accumulation and nociception during irradiation (630 nm at 3.7 J/cm). Despite similar PpIX accumulation, C57 mice exhibited less pain behavior compared with SWISS mice because of light absorption by pigmentation. Irradiation of ALA-treated dorsal root ganglion neurons caused phototoxicity-evoked action potentials (APs) in both mouse strains. The antioxidant L-tryptophan increased the light dose required to elicit such APs. By contrast, the addition of keratinocytes to neuronal cultures decreased the threshold for APs, suggesting a requirement for proliferating cells. Inhibition of fatty acid amide hydrolase, selective antagonism of TRPV1 or the application of lidocaine or its quaternary derivative QX-314, reduced AP frequency, whereas antagonism of TRPA1 had no effect. These results suggest that products of singlet oxygen-mediated lipid peroxidation trigger nociceptor activation via TRPV1. Menthol inhibited phototoxicity-evoked APs and reduced pain behavior when applied topically to mice. These findings suggest that menthol might provide pain relief in patients experiencing PpIX-phototoxicity pain caused by photodynamic therapy or erythropoietic protoporphyria.


Subject(s)
Antipruritics/therapeutic use , Dermatitis, Phototoxic/complications , Menthol/therapeutic use , Pain Threshold/drug effects , Pain/drug therapy , Pain/etiology , Photochemotherapy/adverse effects , Acrylamides/pharmacology , Animals , Animals, Newborn , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Disease Models, Animal , Evoked Potentials/drug effects , HEK293 Cells , Humans , Hyperalgesia/etiology , Lidocaine/therapeutic use , Lipid Metabolism/drug effects , Mice , Mice, Inbred C57BL , Neurons/drug effects , Reactive Oxygen Species/metabolism , TRPV Cation Channels/metabolism
15.
Anesthesiology ; 127(5): 878-889, 2017 11.
Article in English | MEDLINE | ID: mdl-28820778

ABSTRACT

BACKGROUND: Prolonged opioid administration leads to tolerance characterized by reduced analgesic potency. Pain management is additionally compromised by the hedonic effects of opioids, the cause of their misuse. The multifunctional protein ß-arrestin2 regulates the hedonic effects of morphine and participates in tolerance. These actions might reflect µ opioid receptor up-regulation through reduced endocytosis. ß-Arrestin2 also recruits kinases to µ receptors. We explored the role of Src kinase in morphine analgesic tolerance, locomotor stimulation, and reinforcement in C57BL/6 mice. METHODS: Analgesic (tail withdrawal latency; percentage of maximum possible effect, n = 8 to 16), locomotor (distance traveled, n = 7 to 8), and reinforcing (conditioned place preference, n = 7 to 8) effects of morphine were compared in wild-type, µ, µ, and ß-arrestin2 mice. The influence of c-Src inhibitors dasatinib (n = 8) and PP2 (n = 12) was examined. RESULTS: Analgesia in morphine-treated wild-type mice exhibited tolerance, declining by day 10 to a median of 62% maximum possible effect (interquartile range, 29 to 92%). Tolerance was absent from mice receiving dasatinib. Tolerance was enhanced in µ mice (34% maximum possible effect; interquartile range, 5 to 52% on day 5); dasatinib attenuated tolerance (100% maximum possible effect; interquartile range, 68 to 100%), as did PP2 (91% maximum possible effect; interquartile range, 78 to 100%). By contrast, c-Src inhibition affected neither morphine-evoked locomotor stimulation nor reinforcement. Remarkably, dasatinib not only attenuated tolerance but also reversed established tolerance in µ mice. CONCLUSIONS: The ability of c-Src inhibitors to inhibit tolerance, thereby restoring analgesia, without altering the hedonic effect of morphine, makes c-Src inhibitors promising candidates as adjuncts to opioid analgesics.


Subject(s)
Drug Tolerance/physiology , Morphine/pharmacology , Psychomotor Performance/physiology , Reinforcement, Psychology , src-Family Kinases/antagonists & inhibitors , src-Family Kinases/metabolism , Animals , Cell Line, Tumor , Female , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Protein Kinase Inhibitors/pharmacology , Psychomotor Performance/drug effects
16.
AAPS J ; 19(4): 1163-1174, 2017 07.
Article in English | MEDLINE | ID: mdl-28474310

ABSTRACT

The importance of aldehyde oxidase (AOX) is becoming increasingly recognized in the prediction of human pharmacokinetic parameters from animal data. The objectives of these studies were to ascertain whether an in vitro-in vivo correlation existed in the clearance and metabolic pathways of AOX substrates and to establish whether the minipig represented an appropriate non-rodent model for man in the pre-clinical development of drugs metabolized by AOX. Using the AOX substrates carbazeran, 6-deoxypenciclovir and zaleplon, clearance was estimated from in vitro depletion experiments with minipig and human liver cytosol and microsomes and scaled before comparison with data generated in parallel in vivo studies in minipigs. In vitro and in vivo metabolic pathways were characterized by LC-MS/MS. Scaling of in vitro metabolism data to predict in vivo clearance underestimated in vivo values, although the rank order of clearance for the three compounds was preserved. Prediction of human in vivo clearance from scaled minipig in vivo data produced results which correlated well with published clinical values. Overall, this study is the first to compare minipig in vitro metabolism data with in vivo pharmacokinetic data for compounds metabolized by AOX and provides a scientific rationale for the selection of this species as a model for humans in the development of drugs which are substrates of AOX.


Subject(s)
Aldehyde Oxidase/metabolism , Animals , Female , Humans , Male , Microsomes, Liver/enzymology , Substrate Specificity , Swine , Swine, Miniature
17.
Int J Lang Commun Disord ; 52(4): 528-539, 2017 07.
Article in English | MEDLINE | ID: mdl-27859986

ABSTRACT

BACKGROUND: Evidence of the effectiveness of therapy for older children with (developmental) language disorder (DLD), and particularly those with receptive language impairments, is very limited. The few existing studies have focused on particular target areas, but none has looked at a whole area of a service. AIMS: To establish whether for students with (developmental) language disorder attending a specialist school, 1:1 intervention with an SLT during one school term improves performance on targeted areas, compared with untreated control areas. Also, to investigate whether gender, receptive language status, autism spectrum disorder (ASD) status, or educational Key Stage affected their response to this intervention. METHODS & PROCEDURES: Seventy-two students (aged 9-17 years, 88% of whom had receptive language impairments) and all speech and language therapists (SLTs) in our specialist school for children with Language Disorder, most of whom have DLD participated in this study over one school term. During this term, the SLTs devised pre- and post-therapy measures for every student for each target they planned to treat 1:1. In addition, for each target area, a control measure was devised. The targets covered a wide range of speech, language and communication areas, both receptive and expressive. Post-therapy tests were administered 'blind'. OUTCOMES & RESULTS: During the term, SLTs and students worked 1:1 on 120 targets, the majority in the areas of expressive and receptive language. Targets and controls did not differ pre-therapy. Significant progress was seen both on targets (d = 1.33) and controls (d = 0.36), but the targeted areas improved significantly more than the controls with a large and clinically significant effect size (d = 1.06). There was no effect of language area targeted (targets improved more than their controls for all areas). Participants with versus those without receptive language difficulties, co-occurring ASD diagnosis or participants in different educational Key Stages did not differ significantly in terms of the progress they made on target areas. CONCLUSIONS & IMPLICATIONS: Direct 1:1 intervention with an SLT can be effective for all areas of language for older children with (D)LD, regardless of their gender, receptive language or ASD status, or age. This adds to the relatively limited evidence base regarding the effectiveness of direct SLT intervention for school-aged children with (D)LD and for children with receptive language impairments. If direct 1:1 intervention can be effective with this hard-to-treat group, it may well also be effective with younger children with (D)LD. Thus, direct SLT services should be available for school-aged children with (D)LD, including older children and adolescents with pervasive difficulties.


Subject(s)
Child Language , Education, Special/methods , Language Development Disorders/rehabilitation , Language Therapy/methods , Speech Therapy/methods , Speech , Adolescent , Age Factors , Autism Spectrum Disorder/diagnosis , Autism Spectrum Disorder/psychology , Child , Educational Status , Female , Humans , Language Development Disorders/diagnosis , Language Development Disorders/psychology , Male , Program Evaluation , Schools , Time Factors , Treatment Outcome
19.
Sci Signal ; 9(433): ra62, 2016 06 21.
Article in English | MEDLINE | ID: mdl-27330189

ABSTRACT

The receptor tyrosine kinase MET is abundant in many human squamous cell carcinomas (SCCs), but its functional significance in tumorigenesis is not clear. We found that the incidence of carcinogen-induced skin squamous tumors was substantially increased in transgenic MT-HGF (mouse metallothionein-hepatocyte growth factor) mice, which have increased abundance of the MET ligand HGF. Squamous tumors also erupted spontaneously on the skin of MT-HGF mice that were promoted by wounding or the application of 12-O-tetradecanoylphorbol 13-acetate, an activator of protein kinase C. Carcinogen-initiated tumors had Ras mutations, but spontaneous tumors did not. Cultured keratinocytes from MT-HGF mice and oncogenic RAS-transduced keratinocytes shared phenotypic and biochemical features of initiation that were dependent on autocrine activation of epidermal growth factor receptor (EGFR) through increased synthesis and release of EGFR ligands, which was mediated by the kinase SRC, the pseudoproteases iRhom1 and iRhom2, and the metallopeptidase ADAM17. Pharmacological inhibition of EGFR caused the regression of MT-HGF squamous tumors that developed spontaneously in orthografts of MT-HGF keratinocytes combined with dermal fibroblasts and implanted onto syngeneic mice. The global gene expression profile in MET-transformed keratinocytes was highly concordant with that in RAS-transformed keratinocytes, and a core RAS/MET coexpression network was activated in precancerous and cancerous human skin lesions. Tissue arrays revealed that many human skin SCCs have abundant HGF at both the transcript and protein levels. Thus, through the activation of EGFR, MET activation parallels a RAS pathway to contribute to human and mouse cutaneous cancers.


Subject(s)
Carcinoma, Squamous Cell/metabolism , ErbB Receptors/metabolism , Keratinocytes/metabolism , Proto-Oncogene Proteins c-met/metabolism , Signal Transduction , Skin Neoplasms/metabolism , Animals , Carcinoma, Squamous Cell/chemically induced , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , ErbB Receptors/genetics , Gene Expression Regulation, Neoplastic/drug effects , Humans , Keratinocytes/pathology , Mice , Proto-Oncogene Proteins c-met/genetics , Skin Neoplasms/chemically induced , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Tetradecanoylphorbol Acetate/toxicity
20.
Child Abuse Negl ; 53: 17-26, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26563643

ABSTRACT

There is increasing emphasis on the use of evidence-based practices (EBPs) in child welfare settings and growing recognition of the importance of the organizational environment, and the organization's climate in particular, for how employees perceive and support EBP implementation. Recently, Ehrhart, Aarons, and Farahnak (2014) reported on the development and validation of a measure of EBP implementation climate, the Implementation Climate Scale (ICS), in a sample of mental health clinicians. The ICS consists of 18 items and measures six critical dimensions of implementation climate: focus on EBP, educational support for EBP, recognition for EBP, rewards for EBP, selection or EBP, and selection for openness. The goal of the current study is to extend this work by providing evidence for the factor structure, reliability, and validity of the ICS in a sample of child welfare service providers. Survey data were collected from 215 child welfare providers across three states, 12 organizations, and 43 teams. Confirmatory factor analysis demonstrated good fit to the six-factor model and the alpha reliabilities for the overall measure and its subscales was acceptable. In addition, there was general support for the invariance of the factor structure across the child welfare and mental health sectors. In conclusion, this study provides evidence for the factor structure, reliability, and validity of the ICS measure for use in child welfare service organizations.


Subject(s)
Child Protective Services/standards , Child Welfare , Evidence-Based Practice/standards , Adult , Aged , California , Child , Evidence-Based Practice/organization & administration , Female , Health Personnel , Health Plan Implementation/organization & administration , Humans , Illinois , Male , Middle Aged , Oklahoma , Organizational Innovation , Organizational Policy , Reproducibility of Results
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