2†Pathways to detection of non-infectious childhood uveitis in the UK: findings from the UNICORN cohort study.

INTRODUCTION: Prompt detection of childhood uveitis is key to minimising negative impact. From an internationally unique inception cohort, we report pathways to disease detection.UNICORNS is a national childhood non-infectious uveitis study with longitudinal collection of a standardised clinical dataset and patient reported outcomes. Descriptive analysis of baseline characteristics are reported.Amongst 150 recruited children (51% female, 31% non-white ethnicity) age at detection ranged from 2-18yrs (median 10). In 69%, uveitis was diagnosed following onset of symptoms: time from first symptoms to uveitis detection ranged from 0-739days (median 7days), with longer time to detection for those presenting initially to their general practitioner. Non symptomatic children were detected through JIA/other disease surveillance (16%), routine optometry review (5%) or child visual health screening (1%). Commonest underlying diagnoses at uveitis detection were JIA (17%), TINU (9%, higher than pre-pandemic reported UK disease frequency) and sarcoid (1%). 60% had no known systemic disease at uveitis detection. At disease detection, in at least one eye: 34% had structural complications (associated with greater time to detection - 17 days versus 4 days for uncomplicated presentation).The larger relative proportions of children with non-JIA uveitis reported here increase the importance of improving awareness of childhood uveitis amongst the wider clinical communities. There is scope for improvement of pathways to detection. Forthcoming analysis on the full cohort (251 recruited to date across 33 hospitals and 4 nations) will provide nationally representative data on management and the determinants of visual and broader developmental/well-being outcomes.

Stability, antioxidant activity, in vivo safety and efficacy of creams with standardized wild apple fruit extract: a comparison of conventional and biodegradable emulsifiers.

OBJECTIVE: The aim of the study was in vitro and in vivo characterization of cosmetic cream with 6% of standardized wild apple fruit extract, stabilized by conventional non-ionic emulsifier-CEW, in order to determine the influence of emulsifiers (conventional vs. biodegradable) on the characteristics of creams and their effects on the skin. METHODS: Organoleptic and physico-chemical (pH values and electrical conductivity) analysis was performed, determination of fruit acids-FAs content (using HPLC analysis) and estimation of its antioxidant activity-AA (using DPPH test) during 180 days. In vivo study included following examinations: screening of safety profile (after creams application under occlusion during 24 h at human skin); skin moisturizing potential, transepidermal water loss-TEWL, skin pH after 28 days of cream application and hypopigmentation efficacy 7 days of cream application at artificially induced skin hyperpigmentation. RESULTS: Investigated cosmetic cream-CEW showed satisfactory organoleptic, physico-chemical characteristics, stability, FAs content (0.13%) and AA (19.25 ± 0.67 %RSC) after preparation, which remained unchanged over the study period. In vivo investigation revealed absence of skin irritation after CEW's application under occlusion. An increase of skin moisturization (after 14 days ΔEC was 18.52 ± 11.51 and after 28 days of applications 16.52 ± 9.36) during 28 day-study, with unchanged TEWL and skin pH values was shown. Decrease of melanin index was revealed, too (after 7 days ΔMI was -31.40 ± 16.50). CONCLUSION: Cosmetic cream stabilized by conventional emulsifier showed better antioxidant potential and weaker moisturizing and hypopigmentation effects related to the cream with same composition but stabilized by biodegradable emulsifiers. Based on all mentioned above, investigated cosmetic cream might be considered for potential use as modern, stable, safe and efficient cosmetic product in the prevention and/or treatment of oxidative stress-related skin changes and/or damages, for moisturization of dry, even irritated skin as well as for lightening of hyperpigmented skin. RÉSUMÉ: OBJECTIF Le but de l'étude était la caractérisation in vitro et in vivo d'une crème cosmétique contenant 6 % d'extrait normalisé de pomme sauvage, stabilisée par un émulsifiant non ionique conventionnel-CEW, afin de déterminer l'influence des émulsifiants (conventionnels vs biodégradables) sur les caractéristiques des crèmes et les effets sur la peau. MÉTHODES: Des analyses organoleptiques et physico-chimiques (pH et conductivité électrique) ont été effectuées, la détermination de la teneur en acides de fruits et en acides gras polyinsaturés (par CLHP), et l'estimation de sa teneur en activité antioxydante (AA) (à l'aide du test DPPH) pendant 180 jours. L'étude in vivo comprenait les examens suivants : dépistage du profil d'innocuité (après application de crèmes sous occlusion pendant 24 h sur la peau humaine); potentiel d'hydratation de la peau, perte d'eau transépidermique (PETE), pH de la peau après 28 jours d'application de la crème et efficacité de l'hypopigmentation après 7 jours d'application de la crème sur une hyperpigmentation de la peau induite artificiellement. RÉSULTATS: La crème cosmétique-CEW étudiée a montré des caractéristiques organoleptiques, physico-chimiques, une stabilité, une teneur en AG (0,13 %) et en AA (19,25 ± 0,67 % RSC) satisfaisantes après préparation, qui sont demeurées inchangées au cours de la période de l'étude. L'étude in vivo a révélé l'absence d'irritation cutanée après l'application de CEW sous occlusion. Une augmentation de l'hydratation de la peau (après 14 jours de DEC était de 18,52 ± 11,51 et après 28 jours d'applications de 16,52 ± 9,36) pendant l'étude de 28 jours, avec une PETE et des valeurs de pH cutané inchangées, a été démontrée. Une diminution de l'indice de mélanine a été mise en évidence également (après 7 jours, ΔMI était de 31,40 ± 16,50). CONCLUSION: La crème cosmétique stabilisée par un émulsifiant conventionnel a montré un meilleur potentiel antioxydant et des effets d'hydratation et d'hypopigmentation plus faibles par rapport à la crème de même composition mais stabilisée par des émulsifiants biodégradables. D'après les données précédentes, la crème cosmétique étudiée pourrait être considérée comme un produit cosmétique moderne, stable, sûr et efficace dans la prévention et/ou le traitement des changements et/ou dommages cutanés liés au stress oxydatif, pour l'hydratation de la peau sèche, voire irritée, ainsi que pour éclaircir la peau hyperpigmentée.

Adverse events associated with deep brain stimulation in patients with childhood-onset dystonia.

BACKGROUND: Data on pediatric DBS is still limited because of small numbers in single center series and lack of systematic multi-center trials. OBJECTIVES: We evaluate short- and long-term adverse events (AEs) of patients undergoing deep brain stimulation (DBS) during childhood and adolescence. METHODS: Data collected by the German registry on pediatric DBS (GEPESTIM) were analyzed according to reversible and irreversible AEs and time of occurrence with relation to DBS-surgery: Intraoperative, perioperative (<4 weeks), postoperative (4 weeks < 6 months) and long term AEs (>6 months). RESULTS: 72 patients with childhood-onset dystonia from 10 DBS-centers, who received 173 DBS electrodes and 141 implantable pulse generators (IPG), were included in the registry. Mean time of postoperative follow-up was 4.6 ±â€¯4 years. In total, 184 AEs were documented in 53 patients (73.6%). 52 DBS-related AEs in 26 patients (36.1%) required 45 subsequent surgical interventions 4.7 ±â€¯4.1 years (range 3 months-15 years) after initial implantation. The total risk of an AE requiring surgical intervention was 7.9% per electrode-year. Hardware-related AEs were the most common reason for surgery. There was a tendency of a higher rate of AEs in patients aged 7-9 years beyond 6 months after implantation. DISCUSSION: The intraoperative risk of AEs in pediatric patients with dystonia undergoing DBS is very low, whereas the rate of postoperative hardware-related AEs is a prominent feature with a higher occurrence compared to adults, especially on long-term follow-up. CONCLUSION: Factors leading to such AEs must be identified and patient management has to be focused on risk minimization strategies in order to improve DBS therapy and maximize outcome in pediatric patients.

Prospective evaluation of Globus pallidus internus deep brain stimulation in Huntington's disease.

INTRODUCTION: Pharmacological treatment of chorea in Huntington's disease (HD) is often limited by poor efficacy or side effects. Pallidal deep brain stimulation (DBS) has been considered in these patients but experience is so far limited. METHODS: We prospectively evaluated the effects of bilateral DBS of the Globus pallidus internus (GPi) over one year in six severely affected HD patients with treatment refractory chorea in an advanced stage of the disease. Primary endpoint of the study was improvement in chorea. Additionally, we evaluated the effects of GPi DBS on the motor part of the Unified Huntington's Disease Rating Scale (UHDRS), bradykinesia, dystonia, functional impairment, psychiatric and cognitive symptoms. Side effects were systematically assessed. RESULTS: The chorea subscore was significantly reduced postoperatively (-47% six months, -40% twelve months postoperatively). The UHDRS total motor score was significantly reduced at six months postoperatively (- 17%) but the effect was not sustained twelve months after the operation (- 5%). Pallidal DBS did not improve other motor symptoms or functional impairment. There was no effect on psychiatric symptoms or cognition. A number of side effects were noted, especially spasticity in three of the patients. CONCLUSIONS: Pallidal DBS is a treatment option for HD patients with severe pharmacologically refractory chorea. Further studies are needed to define optimal candidates for this procedure.

Transition from paediatric to adult ophthalmology services: what matters most to young people with visual impairment.

PurposeTo identify the views and experiences and thus the transition-related needs of young people with visual impairment (VI), so as to inform future practice and policies.Patients and methodsQualitative study of 17 young people aged 16-19 years (ie the conventional transition age threshold) with VI (best-corrected acuity logMAR worse than 0.48) and without additional impairments, drawn from a sampling frame of paediatric ophthalmology patients attending Great Ormond Street Hospital and Moorfields Eye Hospital (London, UK). In-depth, semistructured interviews were conducted to elicit their experiences, preferences, and attitudes towards transitioning within health care. Qualitative thematic analysis identified themes related to participants' experience of transition.ResultsEight of 17 participants had transitioned out of paediatric ophthalmology services, 7 had not, and 2 were unsure. Their views and experiences varied. Only 2 of those who had transitioned preferred their prior paediatric service, and 1 still in a paediatric services did not want to transition. Age-appropriate communication and physical clinical environment were two key components of care, both associated with greater confidence to self-manage health care in the future as an adult. Emotional attachment to paediatric services/teams was associated with reluctance to transition.ConclusionsGeneric guidance on transition is broadly applicable to children/young people with VI. Age-appropriate communication and appropriate physical clinical environments may be optimally delivered through adolescent ophthalmology services bridging paediatric and adult provision. Lack of research on transitions in paediatric ophthalmology has thus far restricted intervention studies; our findings serve to aid in developing an evidence base to achieve this.

Non-motor symptoms and quality of life in subjects with mild parkinsonian signs.

BACKGROUND: Mild parkinsonian signs (MPS) are frequent in the elderly population and associated with the presence of risk markers for Parkinson's disease (PD). Both MPS and non-motor signs may be present in prodromal PD and may significantly impair quality of life (QoL). OBJECTIVE: To disentangle the contribution of motor impairment and extra-motor manifestations to QoL in subjects with MPS (n=63), manifest PD (n=69), disorders with motor symptoms due to non-neurodegenerative diseases (n=213) and healthy controls (n=258). METHODS: Subjects with MPS, healthy controls, disease controls (patients with motor impairment due to, eg, arthrosis and spondylosis), and PD patients (total n=603) were selected from a large epidemiological longitudinal study, the EPIPARK cohort. Motor function was determined using the UPDRSIII protocol, and information on depressive symptoms, anxiety, sleep, and QoL was assessed via rating scales and data were analyzed. RESULTS: Depressive symptoms, anxiety, and sleep problems were equally frequent in the MPS group and controls. Health-related QoL was slightly reduced in the MPS group. Motor impairment and its extent was comparable between the MPS group and disease controls (UPDRSIII 5-6 points). Higher motor dysfunction was associated with lower QoL. Depressive symptoms, but not anxiety and daytime sleepiness, was significant predictors of general QoL, independent of motor function. CONCLUSIONS: Quality of life is slightly decreased in an elderly population with MPS. QoL is associated with severity of motor impairment but also with non-motor aspects, ie, depressive symptoms. Follow-up studies in large cohorts are warranted to determine the natural course of MPS and its impact on QoL.

One size doesn't fit all: time to revisit patient-reported outcome measures (PROMs) in paediatric ophthalmology?

The purpose of this article is to summarise methodological challenges and opportunities in the development and application of patient reported outcome measures (PROMs) for the rare and complex population of children with visually impairing disorders. Following a literature review on development and application of PROMs in children in general, including those with disabilities and or/chronic condition, we identified and discuss here 5 key issues that are specific to children with visual impairment: (1) the conflation between theoretically distinct vision-related constructs and outcomes, (2) the importance of developmentally appropriate approaches to design and application of PROMs, (3) feasibility of standard questionnaire formats and administration for children with different levels of visual impairment, (4) feasibility and nature of self-reporting by visually impaired children, and (5) epidemiological, statistical and ethical considerations. There is an established need for vision-specific age-appropriate PROMs for use in paediatric ophthalmology, but there are significant practical and methodological challenges in developing and applying appropriate measures. Further understanding of the characteristics and needs of visually impaired children as questionnaire respondents is necessary for development of quality PROMs and their meaningful application in clinical practice and research.

[Evaluation of Psychiatric Disorders on the Basis of a SCID Screening]. / Evaluation psychiatrischer Störungen anhand eines erweiterten SKID-Screenings.

BACKGROUND: Psychiatric symptoms/syndromes such as depression, apathy, anxiety or psychotic episodes are present in a range of neurological disorders including Parkinson's disease. The Structured Clinical Interview for DSM-IV (SCID) represents the gold standard for the assessment of psychiatric disorders but is often too time-consuming for application in clinical practice. METHODS: 66 participants were examined using the screening items and the first two questions of section A of the SCID as well as the complete version of the SCID, part I. The accuracy of the screening and the complete SCID was evaluated, and logistic regression was conducted to analyze factors associated with measure disagreement between the two procedures. RESULTS: Overall, psychiatric disorders were identified by screening in 40/66 (60.6%), as against 31/66 (47.0%) using the complete SCID. Compared to the complete SCID, the sensitivity and specificity of the screening items were 88% and 59%, respectively. CONCLUSION: Based on its good sensitivity, the SCID screening may be used in clinical practice to yield an overview of psychiatric disorders that may require treatment. Due to its moderate specificity, however, the complete version of the SCID should be subsequently used in cases whenever the SCID screening is positive. In any case, the SCID screening must be regarded as inadequate for the detection of psychotic symptoms.

Biochemical mechanisms of pallidal deep brain stimulation in X-linked dystonia parkinsonism.

OBJECTIVE: Invasive techniques such as in-vivo microdialysis provide the opportunity to directly assess neurotransmitter levels in subcortical brain areas. METHODS: Five male Filipino patients (mean age 42.4, range 34-52 years) with severe X-linked dystonia-parkinsonism underwent bilateral implantation of deep brain leads into the internal part of the globus pallidus (GPi). Intraoperative microdialysis and measurement of gamma aminobutyric acid and glutamate was performed in the GPi in three patients and globus pallidus externus (GPe) in two patients at baseline for 25/30 min and during 25/30 min of high-frequency GPi stimulation. RESULTS: While the gamma-aminobutyric acid concentration increased in the GPi during high frequency stimulation (231 ± 102% in comparison to baseline values), a decrease was observed in the GPe (22 ± 10%). Extracellular glutamate levels largely remained unchanged. CONCLUSIONS: Pallidal microdialysis is a promising intraoperative monitoring tool to better understand pathophysiological implications in movement disorders and therapeutic mechanisms of high frequency stimulation. The increased inhibitory tone of GPi neurons and the subsequent thalamic inhibition could be one of the key mechanisms of GPi deep brain stimulation in dystonia. Such a mechanism may explain how competing (dystonic) movements can be suppressed in GPi/thalamic circuits in favour of desired motor programs.

Seeing it my way: living with childhood onset visual disability.

BACKGROUND: Although the significant impact of visual disability in childhood has been widely recognized, children's own perspectives of living with a visual impairment have not been considered. We report the experiences of visually impaired (VI) children and young people aged 10-15 years about growing up with impaired sight. METHODS: The participants were 32 VI children and young people, aged 10-15 years [visual acuity logarithm of minimum angle of resolution (LogMAR) worse than 0.51] recruited through National Health Service (NHS) paediatric ophthalmology and developmental vision clinics and 11 VI pupils aged 12-17 attending a specialist school for pupils with disabilities. Individual semi-structured interviews with participants captured their experiences of living with a visual impairment. A child-centred interview topic guide was developed from a literature review, observations at ophthalmology clinics, consultation with health and education professionals working with VI children and young people, and interviews and a focus group with VI pupils from the specialist school. Collaborative qualitative thematic analysis by three researchers identified emergent themes. NVivo software was used for coding the data. RESULTS: Analysis identified six themes concerning living with a visual impairment: (i) social relationships, participation and acceptance; (ii) independence and autonomy; (iii) psychological and emotional well-being; (iv) aspirations and concerns about the future; (v) functioning - home, school and leisure; and (vi) treatment of eye condition. Key issues included: the importance of family and peer support; balancing independence, support and safety; the emotional burden and adjustment of living with a disability; concerns about education and job prospects in the future; functional restrictions and limitations; and ongoing management of the eye condition. CONCLUSIONS: The findings offer insights into the complex realities of living with visual impairment. They provide the basis for development of patient-reported outcome measures. They can also serve to help enrich the understanding of health professionals working with VI children and young people, potentially enabling them to better support them.

Social communicative variation in 1-3-year-olds with severe visual impairment.

BACKGROUND: Although the social communicative domain is recognized as being at risk in young children with visual impairment (VI), few tools are available for identifying those most at risk or the aspects that are most vulnerable. METHODS: A standard parent interview - Social Communication Interview for young children with visual impairment (SOCI-VI), was developed and tested with 55 parents of 17 profoundly, 15 severely VI and 23 normally sighted children; mean age 22 months (range 10-40 months). The 35-item SOCI-VI 35 showed adequate inter-rater and test-retest reliability (P < 0.001). RESULTS: Thirteen of 35 items discriminated within and between the vision groups (anova P 0.008). The group with profound VI scored significantly lower than the Sighted group on the reduced 13 item SOCI-VI 13 (t-test P 0.002), the disparity being greatest for items exploring joint attention. The reduced SOCI-VI 13 showed adequate internal consistency (Cronbach alpha > 0.75) and concurrent validity with the Vineland adaptation questionnaire within a randomized VI subgroup (r 0.8, P < 0.01). CONCLUSIONS: The study reveals trends in early social communicative development in the young VI population and provides preliminary reliability and validity testing for future research within a clinical context.

Autosomal dominant Parkinson's disease in a large German pedigree.

OBJECTIVE: While several genes have been identified to cause Parkinson's disease (PD), monogenic forms explain only a small proportion of cases. We report clinical and genetic results in a large family with late-onset autosomal dominant PD. METHODS: Thirty-eight family members of a five-generation Northern German PD family underwent a detailed neurologic examination, and transcranial sonography was performed in fifteen of them. Comprehensive mutation analysis of known PD-causing genes and a genome-wide linkage analysis were performed. RESULTS: Late-onset definite PD was found in five subjects with a mean age at onset of 63 years. Another six individuals presented either with probable/possible PD or with subtle parkinsonian signs. Six members with a mean age of 79 years had an essential tremor phenotype. Mode of PD inheritance was compatible with autosomal dominant transmission. One of three examined patients with definite PD demonstrated an increased area of substantia nigra hyperechogenicity upon transcranial sonography. Comprehensive linkage and mutational analysis excluded mutations in known PD-causing genes. Genome-wide linkage analysis suggested a putative disease gene in an 11.3-Mb region on chromosome 7p15-21.1 with a multipoint LOD score of 2.0. CONCLUSIONS: The findings in this family further demonstrate genetic heterogeneity in familial autosomal dominant late-onset PD.

Progression of subtle motor signs in PINK1 mutation carriers with mild dopaminergic deficit.

BACKGROUND: While homozygous mutations in the PINK1 gene cause recessively inherited early-onset Parkinson disease (PD), heterozygous mutations have been suggested as a susceptibility factor. METHODS: To evaluate this hypothesis, 4 homozygous PINK1 patients with PD and 10 asymptomatic carriers of a single heterozygous mutation from a large German family (family W) were included in this study. Clinical follow-up of the heterozygous mutation carriers 3 years after the initial visit included a detailed videotaped neurologic examination using the Unified Parkinson's Disease Rating Scale III protocol and smell and color discrimination testing. At follow-up, PET with 18-fluorodopa (FDOPA) of 13 family members was obtained in order to evaluate the clinical phenotype in light of nigostriatal dopaminergic functioning. The clinical and PET data were compared to those of healthy controls. RESULTS: While there was mild worsening of clinical signs in previously affected heterozygous mutation carriers upon follow-up, 3 additional individuals had newly developed signs of possible PD. Hyposmia was found in 7 of the heterozygous mutation carriers, diminished color discrimination in 4. The homozygous mutation carriers who were all definitely affected with PD showed a severe, 60% decrease of caudate and putaminal FDOPA uptake; heterozygous offspring also had a significant 20% putaminal FDOPA uptake reduction compared to controls. CONCLUSIONS: Our findings strengthen the hypothesis that heterozygous PINK1 mutations act as a susceptibility factor to develop at least subtle Parkinson disease motor and nonmotor signs, as supported by the finding of a reduced striatal dopaminergic FDOPA uptake not only in homozygous but also, albeit to a lesser extent, in heterozygous mutation carriers.

[Amiodarone--pro and con]. / Amjodaron--pro et contra.

OBJECTIVE: To compare and evaluate the data for and against the use of antiarrhythmic agent amiodarone in known cardiological indications. DATA SOURCES: A MEDLINE search was used to identify the articles dealing with amiodarone, published in the last 15 years. STUDY SELECTION: Articles and studies (uncontrolled retrospective and controlled prospective), as well as case reports speaking decidedly for or against amiodarone were scrutinized. DATA EXTRACTION: Simple search, no particular conditions. CONCLUSIONS: Despite very numerous and serious side effects amiodarone is an extraordinary drug and can be recommended for use, provided that the physician is very well acquainted with all implications of its use. Large number of studies on a significant number of patients has proven the efficacy of amiodarone in supraventricular and ventricular arrhythmias of various origin. The drug is particularly suitable for the treatment of ventricular arrhythmia in patients with serious heart failure and impaired function of the left ventricle. It was successfully used in the treatment of malignant ventricular arrhythmias. In patients after myocardial infarction, intravenously administered amiodarone improved the chances of survival as well as the condition of arrhythmia, preventing spreading of the infarction. It is very convenient against ventricular arrhythmia after the successful resuscitation. Short-lasting intravenous administration of amiodarone does not cause serious side effects.

[Radioprotective agents in the decontamination of rats poisoned with percutaneously administered mustard gas]. / Dekontaminacija pacova perkutano trovanih S-iperitom pomocu radioprotektora.

The efficacy of rat skin decontamination by radioprotective agents AET and cystamine were tested. Results were compared to standard decontaminants-alcoholate, clay and fuller's earth. It was found that all the animals decontaminated with standard decontaminants had survived 4 LD50 of poison for 21 days. All the animals poisoned by 6 LD50 had survived for 1 day except for those decontaminated with alcoholate where 50% survived throughout the observation period. Alcoholate and clay protected all, and fuller's earth 70% of animals poisoned by 12 LD50, but no longer than 24 h. AET and cystamine protected all rats from 1.7 LD50 for 3 days, from 1 LD50 for 2 days, and from 2 LD50 for 1 day. When higher doses of poison were used (1.7-6.8 LD50) only partial protection was achieved. Our results support the conclusion that radioprotective agents could be convenient means for improvised decontamination of persons poisoned by sulfur mustard, so additional investigations are necessary.