Exploring the psychometric properties of the Intellectual Disability versions of the Short Warwick-Edinburgh Mental Wellbeing Scale and Kidscreen10, self-reported by adolescents with intellectual disability.

BACKGROUND: There are no validated self-report measures that can be used to assess health and wellbeing in adolescents with intellectual disability (ID). METHOD: The aim of this study was to explore the psychometric properties of two newly adapted self-report health-related quality of life (HRQoL) and mental wellbeing measures: the Intellectual Disability versions of the Short Warwick-Edinburgh Mental Wellbeing Scale (ID-SWEMWBS) and Kidscreen10 (ID-Kidscreen10). For this, we used data from a sample of 427 adolescents (aged 11-19) with ID recruited from special school settings. RESULTS: Confirmatory factor analysis (CFA) was conducted to validate the factor structure of both measures. Internal consistency was assessed using Cronbach's alpha and test-retest reliability was analysed using intra-class correlation coefficients. The internal consistency measured using Cronbach's alpha was found to be in the range of 0.70-0.78, test-retest reliabilities were expressed using intra-class correlation coefficients that were found to be high for both measures (ID-SWEMWBS, 0.758; ID-Kidscreen10, 0.723), and the CFA supported the unidimensional structure of both measures. CONCLUSIONS: The results of this study indicate that the ID-SWEMWBS and ID-Kidscreen10 have very good psychometric properties and can be used as self-report measures to assess HRQoL and mental wellbeing in adolescents with ID.

Involving adolescents with intellectual disability in the adaptation of self-reported subjective well-being measures: participatory research and methodological considerations.

BACKGROUND: The measurement of subjective well-being is challenging with samples of adolescents with intellectual disability (ID) given the cognitive and linguistic difficulties they face in comprehending standardised measures, and as such is primarily based on proxy reports. The lack of appropriate tools needs to be addressed so that adolescents with ID can self-report on their own well-being. The current study reports on the use of participatory research methods to adapt and modify two standardised self-report measures of subjective well-being suitable for completion by adolescents with ID. METHOD: Two special schools were recruited for this study. At each school, staff (n = 15) and pupils aged 11-17 years (n = 35) participated. A series of co-design workshops were conducted to adapt two standardised subjective well-being measures: Kidscreen-10 and short-form Warwick-Edinburgh Mental Well-being Scale. RESULTS: Specific aspects for measure adaption were identified: simplifying the item wording and phrasing; inclusion of pictorial communication symbols and visual prompts to represent the meaning of items; changing of tense of questions from past to present; asking questions rather than statements; reducing 5-point Likert scales to 3-point or dichotomous; presenting one item at a time during administration; and developing alternate formats of the survey to ensure inclusivity. CONCLUSIONS: This paper illustrates the value of using participatory research methods when working alongside adolescents with ID and offers methodological, as well as practical, guidance in the context of adapting subjective self-report measures for this target group, serving as a guide to fellow researchers and clinicians interested in modifying or developing self-report measures for adolescents with ID.

Employing the theory of planned behaviour to design an e-cigarette education resource for use in secondary schools.

BACKGROUND: An extended version of the theory of planned behaviour (TPB) was used to inform the design of a framework for an educational resource around e-cigarette use in young people. METHODS: A sequential exploratory design was employed. In Phase 1, elicited behavioural, normative and control beliefs, via 7 focus groups with 51 participants, aged 11-16 years, identified salient beliefs around e-cigarette use. These were used to construct a questionnaire administered to 1511 young people aged 11-16 years, which determined predictors of e-cigarette use and ever use. In Phase 2, sociodemographic variables, e-cigarette knowledge, access, use, marketing and purchasing of e-cigarettes and smoking behaviour were also gathered. The composite findings from Phase 1 and 2 informed the design of a post primary educational resource in Phase 3 around e-cigarette use. RESULTS: Current e-cigarette use was 4%, with almost 23% reporting ever use, suggesting current use is stable but experimentation may be increasing in this cohort. Sociodemographic variables, knowledge of e-cigarettes, smoking behaviour and TPB variables (direct and indirect measures of attitudes, subjective norm, and perceived behavioural control) accounted for 17% of the variance in current e-cigarette use, with higher intentions to use e-cigarettes within the next month, having the strongest impact on use (p < 0.001), followed by self-efficacy (p = 0.016). Sociodemographic and TPB variables accounted for 65% of the variance in intentions to use e-cigarettes in the next month; current e-cigarette use (p < 0.001), more positive attitudes (p < 0.001), stronger social influence (p < 0.001), higher self-efficacy (p < 0.001), higher control beliefs (p < 0.001) and greater motivation to use e-cigarettes (p < 0.001) were the main predictors of intentions. Phases 1 and 2 informed the mapping of key predictors of intentions and use of e-cigarettes onto the Theoretical Domains Framework, which identified appropriate intervention functions and behaviour change techniques. CONCLUSIONS: This paper is the first to bridge the theoretical-practice gap in an area of significant public health importance through the development of a framework for a novel theory driven school-based educational resource aimed at reducing experimentation and uptake of e-cigarette use in young people.

Predictors of wound leakage in patients undergoing surgery for neck of femur fractures.

AIMS: Persistent wound leakage following joint arthroplasty is a known risk for periprosthetic joint infection. Little is known of the predictors of wound leakage, particularly in patients with a fractured neck of femur. We aimed to determine patient and surgical risk factors for wound leakage in this cohort. MATERIALS AND METHODS: All patients undergoing surgery for a fractured neck of femur at Leicester Royal Infirmary between May and August 2017 were included. Patients were identified from a prospective database and placed into two groups: those with wound leakage later than three days postoperatively and those without leakage. All previously reported potential risk factors for wound leakage were compared between groups using a chi-square test and logistic regression. A Kattan-style nomogram was also created to allow probabilities output for the regression predictive models in a visual representation. RESULTS: Two hundred patients underwent surgery for a fractured neck of femur. Overall, 17% of patients (33/200) developed a persistent leaky wound. A multivariable model highlighted increased age (p = 0.01), raised body mass index (BMI; > 25 kg/m2; p = 0.047), diabetes (p = 0.03) and intramedullary hip screw fixation (p = 0.03) as significant risk factors for wound leakage. Patients with persistent wound leakage had significantly longer hospital admission than those without (p = 0.001). DISCUSSION: Our analysis identified four perioperative risk factors for wound leakage following fractured neck of femur surgery. We also developed a novel tool to identify those patients at highest risk of leakage. Once identified, the aggressive management of certain medical comorbidities in these patients may help to reduce their incidence of wound issues and the prolonged admissions that result.

Neuroradiologic Phenotyping of Galactosemia: From the Neonatal Form to the Chronic Stage.

Galactosemia is a rare genetic condition caused by mutation of enzymes involved in galactose and glucose metabolism. The varying clinical spectrum reflects the genetic complexity of this entity manifesting as acute neonatal toxicity syndrome, requiring prompt diagnosis and treatment, to more insidious clinical scenarios as observed in the subacute and chronic presentations. The current literature predominantly focuses on the long-standing sequelae of this disease. The purpose of this multicenter clinical report comprising 17 patients with galactosemia is to highlight the MR imaging patterns encompassing the whole spectrum of galactosemia, emphasizing the 3 main clinical subtypes: 1) acute neonatal presentation, with predominant white matter edema; 2) subacute clinical onset with a new finding called the "double cap sign"; and 3) a chronic phase of the disease with heterogeneous imaging findings. The knowledge of these different patterns together with MR spectroscopy and the clinical presentation may help in prioritizing galactosemia over other neonatal metabolic diseases and prevent possible complications.

Ten years of enzyme replacement therapy in paediatric onset mucopolysaccharidosis II in England.

The outcome of 110 patients with paediatric onset mucopolysaccharidosis II (MPS II) since the commercial introduction of enzyme replacement therapy (ERT) in England in 2007 is reported. Median length of follow up was 10 years 3 months (range = 1 y 2 m to 18 years 6 month). 78 patients were treated with ERT, 18 had no ERT or disease modifying treatment 7 had haematopoietic stem cell transplant, 4 experimental intrathecal therapy and 3 were lost to follow up. There is clear evidence of improved survival (median age of death of ERT treated (n = 16) = 15.13 years (range = 9.53 to 20.58 y), and untreated (n = 17) = 11.43 y (0.5 to 19.13 y) p = .0005). Early introduction of ERT improved respiratory outcome at 16 years, the median FVC (% predicted) of those in whom ERT initiated <8 years = 69% (range = 34-86%) and 48% (25-108) (p = .045) in those started >8 years. However, ERT appears to have minimal impact on hearing, carpal tunnel syndrome or progression of cardiac valvular disease. Cardiac valvular disease occurred in 18/46 (40%), with progression occurring most frequently in the aortic valve 13/46 (28%). The lack of requirement for neurosurgical intervention in the first 8 years of life suggests that targeted imaging based on clinical symptomology would be safe in this age group after baseline assessments. There is also emerging evidence that the neurological phenotype is more nuanced than the previously recognized dichotomy of severe and attenuated phenotypes in patients presenting in early childhood.

An evaluation of methods for the isolation of nontuberculous mycobacteria from patients with cystic fibrosis, bronchiectasis and patients assessed for lung transplantation.

BACKGROUND: RGM medium is an agar-based, selective culture medium designed for the isolation of nontuberculous mycobacteria (NTM) from the sputum of patients with cystic fibrosis (CF). We evaluated RGM medium for the detection of NTM in patients with CF (405 samples), bronchiectasis (323 samples) and other lung diseases necessitating lung transplantation (274 samples). METHODS: In total, 1002 respiratory samples from 676 patients were included in the study. Direct culture on RGM medium, with incubation at two temperatures (30 °C and 37 °C), was compared with conventional culture of decontaminated samples for acid-fast bacilli (AFB) using both a solid medium (Löwenstein-Jensen medium) and a liquid medium (the Mycobacterial Growth Indicator Tube; MGIT). RESULTS: For all three patient groups, significantly more isolates of NTM were recovered using RGM medium incubated at 30 °C than by any other method (sensitivity: 94.6% vs. 22.4% for conventional AFB culture; P < 0.0001). Significantly more isolates of Mycobacterium abscessus complex were isolated on RGM at 30 °C than by AFB culture (sensitivity: 96.1% vs. 58.8%; P < 0.0001). The recovery of Mycobacterium avium complex was also greater using RGM medium at 30 °C compared to AFB culture (sensitivity: 83% vs. 70.2%), although this difference was not statistically significant and a combination of methods was necessary for optimal recovery (P = 0.21). CONCLUSIONS: In the largest study of RGM medium to date, we reaffirm its utility for isolation of NTM from patients with CF. Furthermore; we show that it also provides an effective tool for culture of respiratory samples from patients with bronchiectasis and other lung diseases.

Clinical spectrum, treatment and outcome of children with suspected diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a treatable chronic disorder of the peripheral nervous system. We retrospectively studied 30 children with a suspected diagnosis of CIDP. The diagnosis of CIDP was compared against the childhood CIDP revised diagnostic criteria 2000. Of the 30 children, five did not meet the criteria and four others met the criteria but subsequently had alternative diagnosis, leaving a total of 21 children (12 male) with CIDP as the final diagnosis. Thirteen children presented with chronic symptom-onset (>8 weeks). The majority presented with gait difficulties or pain in legs (n = 16). 12 children (57%) met the neurophysiological criteria and 18/19 (94%) met the cerebrospinal fluid criteria. Nerve biopsy was suggestive in 3/9 (33%), with magnetic resonance imaging supportive in 9/20 (45%). Twenty-one children received immuno-modulatory treatment at first presentation, of which majority (n = 19, 90%) received IVIG (immunoglobulin) monotherapy with 13 (68%) showing a good response. 8 children received second line treatment with either IVIG or steroids or plasmapharesis (PE) and 4 needed other immune-modulatory agents. During a median follow-up of 3.6 years, 9 (43%) had a monophasic course and 12 (57%) had a relapsing-remitting course. At last paediatric follow up 7 (33%) were off all treatment, 9 (43%) left with no or minimal residual disability and 6 (28%) children were walking with assistance (n = 3) or were non-ambulant (n = 3). Our review highlights challenges in the diagnosis and management of paediatric CIDP. It also confirms that certain metabolic disorders may mimic CIDP.

Overground endoscopy in 311 Thoroughbred racehorses: findings and correlation to resting laryngeal function.

OBJECTIVE: To review a large number of equine overground endoscopy (OGE) examinations to determine the incidence of dynamic upper airway obstructions (DUAO); correlations were explored with laryngeal endoscopy findings at rest and abnormal exercising respiratory noise. METHODS: Retrospective analysis of horses presenting for OGE because of perceived poor performance and/or history of abnormal exercising respiratory noise between 2010 and 2014. Signalment, history and examination findings during resting laryngeal endoscopy and OGE were reviewed. RESULTS: Of the total examinations, 311 were reviewed. One or more DUAO were found in 249/311 horses. From 210 males (colts and geldings), 121 had arytenoid cartilage collapse (ACC) and 111 had vocal fold collapse (VFC). From 101 females, 25 had intermittent dorsal displacement of the soft palate (DDSP). Resting laryngeal function grade 4 was found in 121/311 of the study population and 92/210 of males. An association was found between horses with lower resting arytenoid abduction ability to dynamic ACC and higher resting arytenoid abduction ability with DDSP. Abnormal exercising respiratory noise was positively associated with the presence of DUAO. CONCLUSIONS: Multiple DUAO in association with abnormal exercising respiratory noise was a common finding in horses examined for poor performance. This study highlights the importance of OGE in accurately diagnosing the nature of DUAO associated with poor performance.

Risk factors for intramedullary nail breakage in proximal femoral fractures: a 10-year retrospective review.

INTRODUCTION Intramedullary nailing is a common treatment for proximal femoral fractures. Fracture of the nail is a rare but devastating complication that exposes often frail patients to complex revision surgery. We investigated which risk factors predict nail failure. METHODS We reviewed all cases of nail breakage seen over a 10-year period in a single busy trauma unit; 22 nail fractures were seen in 19 patients. Comparison was made with a group of 209 consecutive patients who underwent intramedullary fixation of a proximal femur fracture with no nail breakage over a 2-year period. RESULTS In the fractured nail group, mean age was 70.4 years (range 55-88 years).The mean time to fracture was 10 months (range 2.5-23 months). Logistical regression was used to show that low American Society of Anesthesiologists (ASA) score, subtrochanteric fracture and pathological fracture were independent risk factors for nail fracture. CONCLUSIONS Young patients with a low ASA score are at highest risk of nail breakage. We advise close follow-up of patients with these risk factors until bony union has been achieved. In addition, there may be merit in considering other treatment options, such as proximal femoral replacement, especially for those with pathological fracture with a good prognosis.

Changes in movement symmetry over the stages of the shoeing process in military working horses.

Military working horses perform a high proportion of work on road surfaces and are shod frequently to deal with high attrition rates. The authors investigate the influence of shoeing on movement symmetry as an indirect indicator of mechanical differences affecting force production between contralateral limbs. In this quantitative observational study, inertial sensor gait analysis was performed in 23 Irish sport type horses (4-21 years, 1.58-1.85 m) in full ceremonial work at the King's Troop, Royal Horse Artillery. Changes in two movement symmetry measures (SI: symmetry index; MinDiff: difference between displacement minima) for head and pelvic movement were assessed at four stages of routine shoeing: 'old shoes', 'shoes removed', 'trimmed', 'reshod'. Horses were assessed applying shoes to the front limbs (N=10), to the hindlimbs (N=10) or both (N=3). Changes in head movement symmetry between conditions were small and inconsistent. Changes in pelvic movement symmetry were small and showed significant differences between shoeing stages (SI: P=0.013, MinDiff: P=0.04) with most symmetrical pelvic movement after trimming. In military working horses with high frequency shoeing small changes in movement symmetry were measured. All significant changes involved trimming, which indicates that future studies should in particular assess changes before/after trimming and investigate longer shoeing intervals.

Response of 33 UK patients with infantile-onset Pompe disease to enzyme replacement therapy.

BACKGROUND: Enzyme replacement therapy (ERT) for infantile-onset Pompe disease has been commercially available for almost 10 years. We report the experience of its use in a cohort treated at three specialist lysosomal treatment centres in the UK. METHODS: A retrospective case-note review was performed, with additional data being gathered from two national audits on all such patients treated with ERT. The impact on the outcome of various characteristics, measured just prior to the initiation of ERT (baseline), was evaluated using logistic regression. RESULTS: Thirty-three patients were identified; 13/29 (45%) were cross-reactive immunological material (CRIM) negative, and nine were immunomodulated. At baseline assessment, 79% were in heart failure, 66% had failure to thrive and 70% had radiological signs of focal pulmonary collapse. The overall survival rate was 60%, ventilation-free survival was 40% and 30% of patients were ambulatory. Median follow-up of survivors was 4 years, 1.5 months (range 6 months to 13.5 years). As with previous studies, the CRIM status impacted on all outcome measures. However, in this cohort, baseline failure to thrive was related to death and lack of ambulation, and left ventricular dilatation was a risk factor for non-ventilator-free survival. CONCLUSION: The outcome of treated patients remains heterogeneous despite attempts at immunomodulation. Failure to thrive at baseline and left ventricular dilation appear to be associated with poorer outcomes.

FUNGAL SYMBIONTS. Global assessment of arbuscular mycorrhizal fungus diversity reveals very low endemism.

The global biogeography of microorganisms remains largely unknown, in contrast to the well-studied diversity patterns of macroorganisms. We used arbuscular mycorrhizal (AM) fungus DNA from 1014 plant-root samples collected worldwide to determine the global distribution of these plant symbionts. We found that AM fungal communities reflected local environmental conditions and the spatial distance between sites. However, despite AM fungi apparently possessing limited dispersal ability, we found 93% of taxa on multiple continents and 34% on all six continents surveyed. This contrasts with the high spatial turnover of other fungal taxa and with the endemism displayed by plants at the global scale. We suggest that the biogeography of AM fungi is driven by unexpectedly efficient dispersal, probably via both abiotic and biotic vectors, including humans.

A survey of the management of transient loss of consciousness in the emergency department.

UNLABELLED: Transient loss of consciousness (TLoC) is a common presentation to the emergency department (ED). We sought to evaluate current practice in the management of patients with TLoC presenting to a large, city centre ED, against national standards. METHODS: The ED admissions database was searched to identify all patients attending with TLoC during October 2012. The clinical record of the attendance was reviewed to determine if the initial assessment met national standards. RESULTS: Ninety-one patients had a primary presentation with TLoC, representing 0.95% of ED attendances. Documentation of before/during/after the clinical event and clinical examination were done well. Notable aspects done less well included lying and standing blood pressure and recording of driving status. No patient was discharged from the ED with a copy of their 12-lead electrocardiogram (ECG). Sixty-five patients (71%) were discharged from the ED, with follow-up arranged for 11 (16%). Additional follow-up would have been appropriate in a further 15 cases (28%). CONCLUSION: Several aspects of the initial assessment of TLoC were done well. Areas for improvement include driving status documentation and advice, recording of postural blood pressures and ECG provision on discharge.

Successful reversal of propionic acidaemia associated cardiomyopathy: evidence for low myocardial coenzyme Q10 status and secondary mitochondrial dysfunction as an underlying pathophysiological mechanism.

Dilated cardiomyopathy is a rare complication in propionic acidaemia (PA). Underlying pathophysiological mechanisms are poorly understood. We present a child of Pakistani consanguineous parents, diagnosed with late-onset PA at 18months of age. He presented a mild phenotype, showed no severe further decompensations, normal growth and psychomotor development on a low protein diet and carnitine supplementation. At 15years, a mildly dilated left ventricle was noticed. At 17years he presented after a 2-3month history of lethargy and weight loss with severe decompensated dilated cardiomyopathy. He was stabilised on inotropic support and continuous haemofiltration; a Berlin Heart biventricular assist device was implanted. He received d,l-hydroxybutyrate 200mg/kg/day, riboflavin and thiamine 200mg/day each and coenzyme Q10 (CoQ10). Myocardial biopsy showed endocardial fibrosis, enlarged mitochondria, with atypical cristae and slightly low respiratory chain (RC) complex IV activity relative to citrate synthase (0.012, reference range 0.014-0.034). Myocardial CoQ10 was markedly decreased (224pmol/mg, reference range 942-2738), with a marginally decreased white blood cell level (34pmol/mg reference range 37-133). The dose of CoQ10 was increased from 1.5 to 25mg/kg/day. Cardiomyopathy slowly improved allowing removal of the external mechanical cardiac support after 67days. We demonstrate for the first time low myocardial CoQ10 in cardiomyopathy in PA, highlighting secondary mitochondrial impairment as a relevant causative mechanism. According to these findings, a high-dose CoQ10 supplementation could be a potential adjuvant therapeutic to be considered in PA-related cardiomyopathy.

Revisiting the phylogeography and demography of European badgers (Meles meles) based on broad sampling, multiple markers and simulations.

Although the phylogeography of European mammals has been extensively investigated since the 1990s, many studies were limited in terms of sampling distribution, the number of molecular markers used and the analytical techniques employed, frequently leading to incomplete postglacial recolonisation scenarios. The broad-scale genetic structure of the European badger (Meles meles) is of interest as it may result from historic restriction to glacial refugia and/or recent anthropogenic impact. However, previous studies were based mostly on samples from western Europe, making it difficult to draw robust conclusions about the location of refugia, patterns of postglacial expansion and recent demography. In the present study, continent-wide sampling and analyses with multiple markers provided evidence for two glacial refugia (Iberia and southeast Europe) that contributed to the genetic variation observed in badgers in Europe today. Approximate Bayesian computation provided support for a colonisation of Scandinavia from both Iberian and southeastern refugia. In the whole of Europe, we observed a decline in genetic diversity with increasing latitude, suggesting that the reduced diversity in the peripheral populations resulted from a postglacial expansion processes. Although MSVAR v.1.3 also provided evidence for recent genetic bottlenecks in some of these peripheral populations, the simulations performed to estimate the method's power to correctly infer the past demography of our empirical populations suggested that the timing and severity of bottlenecks could not be established with certainty. We urge caution against trying to relate demographic declines inferred using MSVAR with particular historic or climatological events.

Intellectual and neurological functioning in Morquio syndrome (MPS IVa).

Mucopolysaccharidosis type IVa (MPS IVa, Morquio syndrome OMIM #253000) is a lysosomal storage disease caused by deficiency in N-acetylgalactosamine-6-sulfatase (GALNS, EC 3.1.6.4; encoded by GALNS gene at 16q24.3). Unlike other MPS disorders involving excessive heparan and dermatan sulfate, Morquio syndrome has not been associated with neurological involvement nor with intellectual impairment as this disorder of keratan sulfate has been described as a purely visceral and skeletal disorder. Neurocognitive assessment was undertaken of MPS IVa patients with age appropriate intellectual tests as well as a Child Behaviour Checklist as part of clinical follow up. Available neuroimaging studies (MRI and MR spectroscopy) were reviewed. Whilst more than half of the overall IQ scores fell in the average range, scores for 3/8 children fell below average. A number of behavioural problems were highlighted, including anxiety/depression, attention and somatic complaints. Subtle neuroimaging abnormalities were demonstrated in over half of the children. These findings present a challenge to existing assumptions about the nature of Morquio A syndrome. A hypothesis regarding the potential role of calcium signalling is explored.

Mutant allele-specific imbalance modulates prognostic impact of KRAS mutations in colorectal adenocarcinoma and is associated with worse overall survival.

The prognostic impact of distinct KRAS mutations in colorectal carcinomas is not fully characterized. We hypothesized that the prognostic impact of KRAS mutations is modulated by KRAS mutant allele-specific imbalance (MASI). KRAS MASI was assessed by sequencing electropherograms in KRAS-mutated colorectal carcinomas (N = 394, prospectively tested). The mechanism of KRAS MASI was studied by fluorescence in situ hybridization (FISH; N = 50). FISH showed that KRAS MASI developed by chromosome 12 hyperploidy (9/18, 50%) or KRAS amplification (1/18, 5.5%). KRAS MASI was more common in tumors with KRAS codon 13 than with codon 12 mutations [24/81, 30% vs. 54/313, 17%; odds ratio (OR), 2.0, 95% confidence interval (CI), 1.2-3.5; p = 0.01]. KRAS MASI was correlated with overall survival (N = 358, median follow-up = 21 months). In a multivariate analysis, KRAS codon 13 MASI was an independent adverse prognostic factor (compared to codon 13 mutants without MASI combined with all codon 12 mutants; adjusted hazard ratio, 2.2, 95% CI: 1.2-3.9; p = 0.01). KRAS MASI arises through chromosome 12 hyperploidy or KRAS amplification and, when affects KRAS codon 13, is associated with worse overall survival.