Quality of life in neurofibromatosis 1: development and validation of a tool dedicated to cutaneous neurofibromas in adults.

BACKGROUND: Cutaneous neurofibromas (cNF), present in 95% of individuals with neurofibromatosis 1 (NF1), are considered as one of the greatest medical burden because of physical disfigurement. No specific score evaluates their impact on quality of life (QoL). OBJECTIVE: To develop a specific score assessing cNF-related QoL. METHODS: Through a multidisciplinary workshop including 10 patients, 3 expert-in-NF1 physicians, 3 health care workers (nurses and psychologist) and 1 methodologist, the French version of the Skindex-16 was modified by adding 3 items. The new cNF-Skindex was validated among patients with NF1 recruited in the ComPaRe online cohort, in France (N = 284). Construct validity was assessed by comparing it with the EQ-5D-5L, its visual analogue scale and the MYMOP2 and by assessing its association with patients' characteristics. Reliability was assessed by a test-retest. An English version of the tool was developed using a back-forward translation. RESULTS: A total of 228 individuals with NF1, with cNF answered the 19-item questionnaire. These items fitted into 3 domains: emotions, symptoms, functioning. One was dropped during analysis because >90% responders were not concerned. The cNF-Skindex significantly correlated with the EQ-5D-5L (N = 193) and MYMOP2 (N = 210) indicating good external validity: rs 0.38 (P < 0.001), and 0.58 (P < 0.001), respectively. Having >50 cNF was the only independent variable associated with the total score cNF-Skindex (ß = 15.88, 95%CI 6.96-24.81, P = 0.001), and with the 3 sub-scores: 'functioning' (ß = 2.65, 95%CI 0.71-4.59, P = 0.008), 'emotions' (ß = 17.03, 95%CI 4.11-29.96, P = 0.010) and 'symptoms' (ß = 3.90, 95%CI 1.95-5.85, P < 0.001). Test-retest reliability (N = 133) found an ICC at 0.96 demonstrating good reproducibility. CONCLUSION: The cNF-Skindex demonstrated excellent psychometric properties. The global and sub-scores were increased with higher number of cNF arguing for its use in further trials aiming to reduce their number or prevent their development. Cross-cultural validation and evaluation of its responsiveness are the next steps.

Vitiligo Treatment Impact score (VITs): development and validation of a vitiligo burden of treatment questionnaire using the ComPaRe Vitiligo e-cohort.

BACKGROUND: Vitiligo management is challenging and requires long-term adherence of patients who often complain of the burden associated with treatment. OBJECTIVE: To develop and validate a patient reported measurement of the burden of treatment in vitiligo. METHODS: The study was nested within the ComPaRe Vitiligo e-cohort, an online e-cohort of vitiligo patients in France. Items were derived from a literature review and from the qualitative analysis of a survey using open-ended questions of 204 patients with Vitiligo. Construct validity of the resulting instrument was assessed by comparing the instrument's score to the Dermatology Life Quality Index (DLQI), Vitiligo Impact Patient score (VIPs) and Treatment Burden Questionnaire (TBQ) scores. Reliability was assessed by test-retest with 15 ± 10 days of interval between both assessments. RESULTS: In total, 343 adult participants participated in the validation of the Vitiligo Treatment Impact score (VITs). The VITs is a 19-item questionnaire assessing the burden of treatment in patients with vitiligo with results suggesting four domains ('Finding a doctor', 'Phototherapy', 'Topical treatment' and 'Impact on outdoor activities and photoprotection'). The VITs total score was well correlated with the DLQI, VIP and TBQ scores. Agreement between test and retest was good (ICC 0.705, 95% CI 0.491-0.818). CONCLUSIONS: We developed a patient reported measurement of the burden of treatment in vitiligo with good psychometric properties.

Development of a shared decision-making tool in vitiligo: an international study.

BACKGROUND: Shared decision-making tools (SDMt) are visual tools developed to promote joint medical decisions between physicians and patients. There is a paucity of such tools in dermatology. OBJECTIVES: To develop and validate a SDMt for use in specialized consultation for vitiligo. METHODS: A prospective cross-sectional study was carried out from March 2019 to March 2020. We first conducted a qualitative study of topics discussed by patients and clinicians during therapeutic decision-making in the setting of a specialized consultation for vitiligo using an anchored-theory method, which allowed conceptualization of the SDMt. The usefulness of the SDMt was evaluated by a working group of multidisciplinary health workers and patients with vitiligo. Consensus on the final tool was obtained through an e-Delphi method. RESULTS: We recruited 30 patients with vitiligo for the qualitative study, which identified 91 topics related to therapeutic decision-making. Hierarchical clustering analysis confirmed the distribution of these topics in two subgroups (general treatment goals and priorities, and topics specific to each treatment). The consensus of a multidisciplinary group was used to develop the SDMt. The tool was comprised of eight A5 cards, which addressed face repigmentation; body repigmentation (limited area); body repigmentation (extended area); partial or complete depigmentation; coping with the disease; stabilization of disease; maintaining repigmentation; and disease information. Cognitive interviews confirmed the satisfaction, readability and usefulness of the SDMt. The SDMt was then translated and culturally validated in English. CONCLUSIONS: We developed a tool for shared decision-making in nonsegmental vitiligo, which we translated and cross-culturally validated in a US patient population with vitiligo to ensure its generalizability.

Correlates of body mass index among primary school children in Ho Chi Minh City, Vietnam.

OBJECTIVES: To document the prevalence of overweight and obesity and examine associated risk factors. STUDY DESIGN: A cross-sectional survey was conducted in 16 primary public schools in eight districts of Ho Chi Minh City in 2016. A multistage clustering sampling method was used to collect a sample of 1806 pupils attending the first, second, and third grades (7-9 years). METHODS: Age- and sex-adjusted body mass index (BMI) status was defined using International Obesity Taskforce cut-offs. Ordered probit regression models were used to assess the association between child BMI and its socio-economic and demographic risk factors. The model was estimated separately for boys and girls to assess the extent to which the socio-economic gradients in BMI vary by gender. RESULTS: The prevalence of obesity among boys was twice the rate for girls (24.7 vs 12.3%). The prevalence of overweight and obesity were also higher among pupils attending schools located in urban districts than in semi-rural districts. Gender, household wealth, the frequency of having breakfast at home, parental body weight, and school location were strong predictors of child BMI status. The protective effect of having breakfast more frequently at home against the risk of overweight/obesity was more pronounced in girls than in boys. Father's body weight and child BMI were more strongly associated with boys from poorer households than boys from wealthier households, while the differences were not significant for girls. CONCLUSIONS: The high prevalence of childhood overweight and obesity indicates an urgent need for more gender-specific, effective intervention, and prevention programs.

Statistical controversies in clinical research: comparison of primary outcomes in protocols, public clinical-trial registries and publications: the example of oncology trials.

Background: Protocols are often unavailable to peer-reviewers and readers. To detect outcome reporting bias (ORB), readers usually have to resort to publicly available descriptions of study design such as public clinical trial registries. We compared primary outcomes in protocols, ClinicalTrials.gov and publications of oncology trials and evaluated the use of ClinicalTrials.gov as compared with protocols in detecting discrepancies between planned and published outcomes. Method: We searched for phase III oncology trials registered in ClinicalTrials.gov and published in the Journal of Clinical Oncology and New England Journal of Medicine between January 2014 and June 2015. We extracted primary outcomes reported in the protocol, ClinicalTrials.gov and the publication. First, we assessed the quality of primary outcome descriptions by using a published framework. Second, we evaluated modifications of primary outcomes between each source. Finally, we evaluated the agreement, specificity and sensitivity of detecting modifications between planned and published outcomes by using protocols or ClinicalTrials.gov. Results: We included 65 trials, with 81 primary outcomes common among the 3 sources. The proportion of primary outcomes reporting all items from the framework was 73%, 22%, and 75% for protocols, ClinicalTrials.gov and publications, respectively. Eight (12%) trials presented a discrepancy between primary outcomes reported in the protocol and in the publication. Twelve (18.5%) trials presented a discrepancy between primary outcomes registered at ClinicalTrials.gov and in publications. We found a moderate agreement in detecting discrepant reporting of outcomes by using protocols or ClinicalTrials.gov [κ = 0.53, 95% confidence interval (0.25-0.81)]. Using ClinicalTrials.gov to detect discrepant reporting of outcomes showed high specificity (89.5%) but lacked sensitivity (75%) as compared with use of protocols. Conclusion: In oncology trials, primary outcome descriptions in ClinicalTrials.gov are often of low quality and may not reflect what is in the protocol, thus limiting the detection of modifications between planned and published outcomes.

[Clinical characteristics and follow-up of 60 patients with recent diagnosis of giant cell arteritis, NEWTON study]. / Caractéristiques et profils évolutifs des patients avec un diagnostic récent d'artérite à cellules géantes, étude NEWTON.

INTRODUCTION: The management of giant cell arteritis (GCA) has evolved with the arrival of tocilizumab (TCZ) and the use of PET/CT. Our objective is to describe the characteristics and followup of patients with recent diagnosis of GCA in current care. PATIENTS AND METHODS: The NEWTON cohort is a monocentric retrospective cohort based on data collected from 60 GCA patients diagnosed between 2017 and 2022 according to the ACR/EULAR 2022 criteria. RESULTS: The median age at diagnosis was 73 [68.75; 81] years old. At diagnosis, the main manifestations were unusual temporal headaches in 48 (80 %) and an inflammatory syndrome in 50 (83 %) patients. Temporal artery biopsy confirmed the diagnosis in 49/58 (84 %) patients. Doppler of the temporal arteries found a halo in 12/23 (52 %) patients. The PET/CT found hypermetabolism in 19/43 (44 %) patients. Prednisone was stopped in 17.5 [12.75; 24.25] months. During follow-up, 22 (37 %) patients received TCZ. At least one complication of corticosteroid therapy was observed in 22 (37 %) patients. After a median follow-up of 24 [12; 42] months, 25 (42 %) patients relapsed. At the end of the follow-up, 29 (48.3 %) patients were weaned from corticosteroid therapy and 15 (25 %) were on TCZ. CONCLUSION: Despite the increasing use of TCZ in the therapeutic arsenal and of the PET/CT in the imaging tools of GCA patients, relapses and complications of corticosteroid therapy remain frequent, observed in more than a third of patients.

Sinus arrest in familial hypokalemic periodic paralysis caused by SCN4A mutation: a case report.

BACKGROUND: Primary hypokalemic periodic paralysis (HypoPP), a rare skeletal muscle channelopathy resulting in episodic muscle weakness or paralysis under hypokalemic conditions, is caused by autosomal-dominant genetic mutations. HypoPP limits physical activity, and cardiac arrhythmias during paralytic attacks have been reported. We describe a rare familial HypoPP case complicated by sinus arrest and syncope requiring urgent temporary pacemaker implantation. CASE REPORT: A 27-year-old Vietnamese man with a family history of periodic paralysis presented with his third attack of muscle weakness triggered by intense football training the previous day. Clinical and laboratory features justified a HypoPP diagnosis. During intravenous potassium replacement, the patient experienced syncopal sinus arrest requiring urgent temporary pacemaker implantation. The patient gradually improved, responding favorably to oral potassium supplements. Genetic testing revealed an Arg1132Gln mutation in the sodium ion channel (SCN4A, chromosome 17: 63947091). At discharge, the patient received expert consultation regarding nonpharmacological preventive strategies, including avoidance of vigorous exercise and carbohydrate-rich diet. CONCLUSIONS: No evidence has established a relationship between hypokalemia and sinus arrest, and no specific treatment exists for familial HypoPP due to SCN4A mutation. Clinician awareness of this rare condition will promote appropriate diagnostic approaches and management strategies for acute paralytic attacks. Treatment should be tailored according to HypoPP phenotypes and genotypes.

Plasma electron source for generating a ribbon beam in the forevacuum pressure range.

We describe a plasma-cathode electron beam source based on a hollow cathode glow discharge and operating in the forevacuum pressure range that produces a steady-state ribbon beam. The electron beam is generated in the pressure range of 10-30 Pa. A multi-aperture electron extraction and beam formation system is used to provide beam stability and enhanced uniformity of beam current density, allowing the use of this kind of device for beam-plasma surface modification over relatively large areas.

Two types of somatostatin receptors differentiated by cyclic somatostatin analogs.

Somatostatin receptors in rat brain, pituitary, and pancreas were labeled with two radioiodinated analogs of somatostatins 14 and 28. Two cyclic analogs of somatostatin, SMS201-995 and cyclo(Ala-Cys-Phe-D-Trp-Lys-Thr-Cys), showed biphasic displacement of binding to somatostatin receptors by these radioligands. In contrast, all other somatostatin analogs, including somatostatin-14, competed for the receptor sites with monophasic displacement of radioligand receptor binding. Thus two types of somatostatin receptors were identified. It was found that the pituitary and pancreas have predominantly one type of somatostatin receptor whereas the brain has both, and that different regions of the brain have various proportions of the two types. These findings suggest methods to characterize other types of somatostatin receptors subserving somatostatin's diverse physiological functions, including a potential role in cognitive function and extrapyramidal motor system control.

Reduced numbers of somatostatin receptors in the cerebral cortex in Alzheimer's disease.

Somatostatin receptor concentrations were measured in patients with Alzheimer's disease and controls. In the frontal cortex (Brodmann areas 6, 9, and 10) and temporal cortex (Brodmann area 21), the concentrations of somatostatin in receptors in the patients were reduced to approximately 50 percent of control values. A 40 percent reduction was seen in the hippocampus, while no significant changes were found in the cingulate cortex, postcentral gyrus, temporal pole, and superior temporal gyrus. Scatchard analysis showed a reduction in receptor number rather than a change in affinity. Somatostatin-like immunoreactivity was significantly reduced in both the frontal and temporal cortex. Somatostatin-like immunoreactivity was linearly related to somatostatin-receptor binding in the cortices of Alzheimer's patients. These findings may reflect degeneration of postsynaptic neurons or cortical afferents in the patients' cerebral cortices. Alternatively, decreased somatostatin-like immunoreactivity in Alzheimer's disease might indicate increased release of somatostatin and down regulation of postsynaptic receptors.

Mycotic aneurysm of the descending thoracic aorta. Review and case report.

A 74-year-old male presented with bilateral invalidating claudication. A bilateral percutaneous transluminal angioplasty (PTA) with stenting of both superficial femoral arteries was performed but complicated by an urosepsis with Escherichia coli and a septic phlebitis at the site of an intravenous line. The phlebitis was complicated by a local abcedation for which incision and drainage were performed. One month after discharge he was readmitted at our hospital with septic fever and positive hemocultures for Escherichia coli. Positron emission tomography-computed tomographic scan (PET/CT-scan) showed a mycotic aneurysm of the thoracic aorta. Because no cryopreserved donor aorta was available and the aneurysm size rapidly increased, an open in situ repair was performed with a Dacron silver prosthesis soaked in rifampicin. His recovery was further complicated by a perforated toxic megacolon for which a subtotal colectomy was performed. Further recovery was uncomplicated and 10 months after the aortic repair patient is still free from infection.

Tuning Plasmon Resonance in Magnetoplasmonic Nanochains by Controlling Polarization and Interparticle Distance for Simple Preparation of Optical Filters.

Magnetoplasmonic Fe3O4-coated Ag nanoparticles (NPs) are assembled in large scale (18 × 18 mm2) in order to observe unique modulation of plasmonic coupling and optical tunable application via both external magnetic field and the combination of magnetic dipole and electrostatic interactions of particle-particle and particle-substrate. These large nanochains film exhibits outstanding tunability of plasmonic resonance from visible to near-infrared range by controlling the polarization angle and interparticle distance (IPD). The enormous spectral shift mainly originated from far-field rather than near-field coupling of Ag cores because of the sufficiently large separation between them in which Fe3O4 shell acts as spacer. This tunable magnetoplasmonic film can be applicable in the field of anisotropic optical waveguides, tunable optical filter, and nanoscale sensing platform.

Differential localization of dopamine D1 and D2 receptors in rat retina.

Dopamine interacts with distinct receptors on different target neurons in the rat retina. Dopamine receptors were labeled in the rat retina by autoradiography using 3H-SCH-23390 and 3H-spiperone binding to retinal sections. The 3H-SCH-23390 binding to D1 receptors was most concentrated in the inner plexiform, inner nuclear, and ganglion cell layers; it was absent from the outer nuclear layer and the photoreceptor inner and outer segments. Competition studies indicated that 3H-SCH-23390 binding to the inner retina was inhibited with high affinities by the D1-specific agonist and antagonist, SKF-38393 and SCH-23390. The D2-specific compounds were ineffective in competing for 3H-SCH-23390 binding. The 3H-spiperone binding to D2 receptors, however, was most concentrated in the photoreceptor inner and outer segments and in the outer nuclear layer. The D2-specific agonist and antagonists, such as quinpirole, sulpiride, and eticlopride, competed for 3H-binding with high affinities; SCH-23390 and SKF-38393 were ineffective. The D2 receptors on the photoreceptors had a high affinity for clozapine but lower affinities for the modified benzamides. This is characteristic of a novel subtype of D2 receptors. Thus, D1 and D2 dopamine receptors are localized differentially in the rat retina to mediate different physiologic effects of dopamine.

Postnatal development of the ciliary body and pars plana. A morphometric study in childhood.

The ciliary body of the human eye serves many vital functions and provides important access to the posterior segment of the globe in vitreoretinal surgery. Although embryogenesis and prenatal development of the ciliary body have been well documented, continuing development of the ciliary body during early childhood has not been studied extensively. We determined the lengths of the ciliary body and pars plana in 76 normal eyes of subjects who ranged in age from 1 week to 6 years. The ciliary body was found to be of substantial length soon after birth; it measured a mean of 3.06 mm nasally and 3.31 mm temporally. Three quarters of the final length of the ciliary body at adulthood was achieved by age 24 months. The growth of the ciliary body is discussed in relation to the growth of the eye.

Neurotransmitter receptor localizations: brain lesion induced alterations in benzodiazepine, GABA, beta-adrenergic and histamine H1-receptor binding.

Selective neuronal lesions have been utilized in efforts to localize binding sites in rat brain for beta-adrenergic, gamma-aminobutyric acid (GABA), histamine H1 and benzodiazepine receptors. The various receptors respond differentially to lesions both in extent of change and in time course. After kainate lesions in the corpus striatum, benzodiazepine receptors are depleted up to 45% at 45--78 days but are unaffected after 7 days. By contrast striatal GABA receptors are increased at 7 days but depleted at later times. Thus both striatal benzodiazepine and GABA receptors appear to be associated at least in part with intrinsic neurons. In the cerebellum both benzodiazepine and GABA receptors are reduced in kainate treated rats and in Nervous mice, mutants which lack Purkinje cells. The most pronounced dissimilarity between benzodiazepine and GABA receptors occurs in Weaver mice, which selectively lack granule cells and display a 60% reduction in GABA receptors but a 40% augmentation in benzodiazepine receptors. A major portion of cerebellar GABA receptors, therefore, appear to be localized to granule cells. Striatal beta-adrenergic receptors are reduced following intrastriatal kainate injections but are unaffected by cerebral cortex ablation, suggesting an association with intrinsic neurons but not with axon terminals of the corticostriate pathway. While intraventricular injections of 6-hydroxydopamine enhance [3H]dihydroalprenolol binding to beta-adrenergic receptors in the cerebral cortex and hippocampus, such binding is not augmented in the corpus striatum, brain stem, midbrain or thalamus-hypothalamus by this treatment. Moreover, medial forebrain bundle lesions, which destroy ascending adrenergic neurons, fail to alter cerebral cortical or striatal beta-adrenergic receptors. Thus denervation-elicited increases in beta-adrenergic receptors vary with brain region and the type of denervating lesion. Histamine H1-receptors are the most resistant of all to neuronal lesions. In the corpus striatum [3H]mepyramine binding is unaffected by cerebral cortex ablation, nigral injections of 6-hydroxydopamine or brain stem hemisection. In the hippocampus, medial forebrain bundle lesions, intrahippocampal kainate injection, and fimbria and fornix transection largely fail to alter [3H]mepyramine binding. Accordingly, a major portion of these receptors may be associated with nonneuronal elements such as glia or blood vessels.

Histamine H1-receptors labeled in vivo: antidepressant and antihistamine interactions.

3H-Mepyramine labels specific histamine H1-receptors in brains of mice after intravenous injection. The potencies of H1-antihistamines in reducing 3H-mepyramine binding in vivo correspond to their pharmacological activities and show parallels with their affinities for 3H-mepyramine binding sites in isolated brain membranes. Several antidepressants are potent in competing for 3H-mepyramine binding in vivo as well as in vitro.

[3H]doxepin interactions with histamine H1-receptors and other sites in guinea pig and rat brain homogenates.

[3H]Doxepin, a tricyclic antidepressant, binds to brain homogenates with two saturable components. The high affinity component, with a dissociation constant (KD) of 0.26 nM, is associated with histamine H1-receptors. This high affinity binding shows stereospecificity in that d-chlorpheniramine is 100 times more potent than the pharmacologically less active l-isomer. Its drug specificity and regional variation closely parallel those exhibited by [3H]mepyramine binding. The drug specificity of the low affinity component is distinct from that of histamine H1-receptors, with no stereospecificity for chlorpheniramine isomers. Furthermore, all the H1-histamine antagonists tested display micromolar potency at the low-affinity doxepin sites but nanomolar potency at the high-affinity doxepin sites associated with a physiological histamine H1-receptor. The drug specificity of the low affinity site does not correspond to that of any known neurotransmitter receptor. Tricyclic antidepressants display IC50 values of 30-600 nM for the inhibition of [3H]doxepin binding to the low-affinity component with most values in the 0.1-0.3 microM affinity range.