In children and adolescents with temporomandibular disorder assembled with juvenile idiopathic arthritis ‑ no association were found between pain and TMJ deformities using CBCT

Background - Children and adolescents with juvenile idiopathic arthritis (JIA) may suffer from temporomandibular disorder (TMD). Due to this, imaging diagnosis is crucial in JIA with non-symptomatic TM joint (TMJ) involvement. The aim of the study was to examine the association between clinical TMD signs/symptoms and cone-beam computed tomography (CBCT) findings of TMJ structural deformities in children and adolescents with JIA. Methods - This cross-sectional study is part of a longitudinal prospective multi-centre study performed from 2015–2020, including 228 children and adolescents aged 4–16 years diagnosed with JIA, according to the International League of Associations for Rheumatology (ILAR). For this sub-study, we included the Bergen cohort of 72 patients (32 female, median age 13.1 years, median duration of JIA 4.5 years). Clinical TMD signs/symptoms were registered as pain on palpation, pain on jaw movement, and combined pain of those two. The severity of TMJ deformity was classified as sound (no deformity), mild, or moderate/severe according to the radiographic findings of CBCT. Results Conclusions - There was no association between painful TMD and CBCT imaging features of the TMJ in patients with JIA, but the oligoarticular subtype of JIA, there was a significant difference associated with TMJ pain and structural CBCT deformities

Oral health-related quality of life, impaired physical health and orofacial pain in children and adolescents with juvenile idiopathic arthritis – a prospective multicenter cohort study

Background - Knowledge on oral health-related quality of life (OHRQoL) in children and adolescents with juvenile idiopathic arthritis (JIA) is limited, and longitudinal studies are lacking. We aimed to describe OHRQoL in children and adolescents with JIA compared to controls, and to explore the validity and internal consistency of the Early Childhood Oral Health Impact Scale (ECOHIS) and the Child Oral Impact on Daily Performance (Child-OIDP). Furthermore, we wanted to investigate associations between OHRQoL and orofacial pain, physical health, disease activity, and temporomandibular joint (TMJ) involvement in JIA. Methods - The Norwegian prospective, multicenter cohort study recruited participants with JIA between 4 and 16 years of age and corresponding controls from three pediatric university hospital departments and public dental health services. In the present study, we analyzed OHRQoL in all children  Results - The same OHRQoL questionnaire was completed both at first visit and two-year follow-up in 101 children  0: JIA group 81% and 85%, p = 0.791; control group 65% and 69%, p = 0.815), while adolescents with JIA reported fewer impacts at the two-year follow-up (Child OIDP > 0: JIA group 27% and 15%, p = 0.004; control group 21% and 14%, p = 0.230). The internal consistency of the OHRQoL instruments was overall acceptable and the criterion validity indicated that the instruments were valid at both visits. Orofacial pain was more frequent in children and adolescents with JIA than in controls. We found associations between OHRQoL impacts and orofacial pain, impaired physical health, disease activity, and TMJ involvement. Conclusions - Children and adolescents with orofacial pain or impaired physical health were more likely to report impacts on daily life activities than those without. Pediatric rheumatologists and dentists should be aware of impaired OHRQoL in individuals with JIA with active disease or temporomandibular joint involvement

Efficacy and safety of intraarticular corticosteroid injections in adolescents with juvenile idiopathic arthritis in the temporomandibular joint: a Norwegian 2-year prospective multicenter pilot study

Background Intraarticular corticosteroids (IACs) have been used to treat temporomandibular joint (TMJ) arthritis. However, prospective clinical studies with magnetic resonance imaging (MRI) scoring are lacking. The aim of this study was to examine efficacy and safety of a single IAC in the TMJ in adolescents with juvenile idiopathic arthritis (JIA) in a clinical setting. Methods In this Norwegian prospective multicenter pilot study 15 patients with JIA (mostly persistent oligoarthritis or RF negative polyarthritis categories) and a clinically and MRI-verified diagnosis of TMJ arthritis were treated with IACs and followed for 2 years. Demographics, systemic medication, general disease activity and outcome measures were recorded including a pain-index score and maximal incisal opening (MIO). Inflammation and bone damage scores were assessed, using two recently published MRI scoring systems with masked radiological evaluation. Results Among the 15 patients, 13 received a single IAC (5 bilateral), and 2 repeated IACs once unilaterally. Thus, the total number of IACs was 22. Median age was 15 years and the majority had an age not thought of as critical regarding mandibular growth retardation due to steroid injection. During the 2-year observation period systemic medication with disease modifying antirheumatic drugs (DMARDs) including biologics was initiated or adjusted in 10/15 (67%) patients. At the 2-months study visit after injection we observed a minimal improvement in MIO from median 44 (1st, 3rd quartiles; 36, 48) mm to 45 (43, 47) mm, p = 0.045 and decreased MRI mean additive inflammatory score from 4.4 ± 1.8 standard deviations (SD) to 3.4 ± 2.0, p = 0.040. From baseline to the 2-months follow-up pain improved in 6/11 patients but pain scores were not significantly improved. MRI-assessed damage increased in two patients with repeated IACs, and decreased in 3 patients but most of the patients were stable over the 2-year follow-up. Intra-rater repeatability of the MRI scoring system domains varied from poor to excellent. Conclusions In this pilot study of predominately single IACs to the TMJ in combination with systemic treatment we observed improvement in MRI-assessed inflammation, mostly stable condylar bone conditions and minimal clinical improvement in adolescents with JIA and TMJ arthritis. No severe side effects were seen.publishedVersio

Oral health-related quality of life in 4-16-year-olds with and without juvenile idiopathic arthritis

Background: Few studies have investigated oral health-related quality of life (OHRQoL) in young individuals with juvenile idiopathic arthritis (JIA). Aims were to investigate whether OHRQoL differs between children and adolescents with JIA compared to controls without JIA, while adjusting for socio-demographic-, behavioral- and oral health-related covariates. Furthermore, to explore whether socio-behavioral and oral health-related covariates of OHRQoL vary according to group affiliation and finally, specifically for individuals with JIA, to investigate whether disease-specific features associate with OHRQoL. We hypothesized that participants with JIA have poorer OHRQoL compared to participants without JIA. Methods: In this comparative cross-sectional study participants with JIA (n = 224) were matched to controls without JIA (n = 224). OHRQoL was assessed according to Early Childhood Oral Health Impact Scale (ECOHIS) (4–11-years-olds) and the child version of Oral Impacts on Daily Performances (Child-OIDP) (12–16-years-olds). JIA-specific characteristics were assessed by pediatric rheumatologists and socio-demographic, behavioral and self-reported oral health information collected by questionnaires. Index teeth were examined for caries by calibrated dentists. Multiple variable analyses were performed using logistic regression, reporting odds ratio (OR) and 95% confidence interval (CI). Two-way interactions were tested between group affiliation and the socio-behavioral- and oral health-related variables on the respective outcome variables. Results: In total, 96 participants with JIA and 98 controls were evaluated according to ECOHIS, corresponding numbers for Child-OIDP was 125 and 124. Group affiliation was not associated with impaired ECOHIS or Child-OIDP in adjusted analyses (OR = 1.95, 95% CI 0.94–4.04 and OR = 0.99, 95% CI 0.46–2.17, respectively). Female adolescents with JIA were more likely than males to report oral impacts according to Child-OIDP. Continued activity or flare was found to adversely affect Child-OIDP, also self-reported outcome measures in JIA associated with Child-OIDP. Conclusions: This study did not provide consistent evidence to confirm the hypothesis that children and adolescents with JIA are more likely to have impaired OHRQoL compared to their peers without JIA. However, female adolescents with JIA were more likely than males to report impacts on OHRQoL. Furthermore, within the JIA group, adolescents with continued disease activity, flare or reporting pain, physical disability, had higher risk than their counterparts of impaired OHRQoL.publishedVersio

Vitamin D, oral health, and disease characteristics in juvenile idiopathic arthritis: a multicenter cross-sectional study

Background: Vitamin D defciency has been associated with autoimmune diseases and oral health. Knowledge about the association between vitamin D status and oral conditions in JIA is limited. We aimed to investigate vitamin D status in a cohort of Norwegian children and adolescents with JIA and possible associations between serum vitamin D levels, clinical indicators of oral health, and JIA disease characteristics. Methods: This multi-center, cross-sectional study, included individuals with JIA aged 4–16 years from three geographically spread regions in Norway. Demographic data, age at disease onset, disease duration, JIA category, disease status, medication, and vitamin D intake were registered. One blood sample per individual was analyzed for 25(OH) vitamin D, and the level of insufciency was defned asResults: Among the 223 participants with JIA, 97.3% were Caucasians, 59.2% were girls, and median age was 12.6 years. Median disease duration was 4.6 years, and 44.4% had oligoarticular JIA. Mean serum vitamin D level was 61.4 nmol/L and 29.6% had insufcient levels. Vitamin D levels did not difer between sexes, but between regions, isoBMI categories, age groups, and seasons for blood sampling. Insufcient vitamin D levels were associated with dentin caries (adjusted OR 2.89, 95% CI 1.43–5.86) and gingival bleeding (adjusted OR 2.36, 95% CI 1.10–5.01). No associations were found with active JIA disease or more severe disease characteristics. Conclusion: In our study, nearly 30% had vitamin D insufciency, with a particularly high prevalence among adolescents. Vitamin D insufciency was associated with dentin caries and gingival bleeding, but not with JIA disease activity. These results point to the need for a multidisciplinary approach in the follow-up of children with JIA, including an increased focus on vitamin D status and oral health

Naloxone for opioid overdose - Pharmacological aspects and dosing in clinical practice

Dødsfall fra opioidoverdoser er et stort folkehelseproblem og utdeling av nesespray med motgiften nalokson var foreslått som et tiltak for å redde liv. I 2012 fantes det ingen godkjente nesesprayer på markedet. Istedenfor var improviserte, ikke-godkjente sprayer uten vitenskapelig evidens i utstrakt bruk. NTNU startet derfor utviklingen av en slik nesespray. Det overordnede målet med denne doktorgraden var å bidra til evidensbasert behandling av opioidoverdoser med nalokson som nesespray. Nesesprayens opptak ble undersøkt ved at friske frivillige deltok i en åpen, randomisert, treveis overkrysningsstudie. Nesesprayen ble undersøkt i to ulike doser, 0,8 mg og 1,6 mg, og ble sammenlignet med 1,0 mg nalokson intravenøst ved å se på legemiddelkonsentrasjonen i blodet. For å undersøke effekten av nalokson ble det utviklet en modell hvor friske frivillige fikk 1,0 mg nalokson intravenøst samtidig som de fikk en målstyrt infusjon med opioidet remifentanil. Slik kunne effekten av nalokson måles med endring av pupillestørrelse, samtidig som vi tok både arterielle og venøse blodprøver for å måle konsentrasjonen av legemidlene. Gjennom en 5-års observasjonsstudie i ambulansetjenesten i Oslo undersøkte vi også den nåværende bruken av nalokson ved overdoser, og koblet disse dataene mot dødsårsaksregistret. Opptaket av legemidlet gikk raskt og biotilgjengeligheten av nesesprayen var 52-54%. Nesesprayen var godt tolerert og det var ingen alvorlige bivirkninger. Remifentanilinfusjonen gav stabile blodkonsentrasjoner gjennom forsøket. Intravenøs nalokson reverserte raskt effekten av opioidet og effekten varte i 118 minutter. Av 2215 overdosepasienter i Oslo fikk 92% intramuskulær nalokson og startdosene var 0,4 og 0,8 mg. En ukes mortalitet for narkotikautløste dødsfall var 4,1/1000 tilfeller. Ingen av dødsfallene var på grunn av reintoksikasjon. Nesesprayen hadde raskt, systemisk opptak og høyere biotilgjengelighet enn improviserte nesesprayer. Dette indikerer at en optimalisert nesespray kan gi en terapeutisk dose nalokson. En målstyrt remifentanil infusjon gav stabile konsentrasjoner av opioidet i blodet og kan være en nyttig modell for å teste nye naloksonprodukter. I ambulansetjenesten var intramuskulær nalokson i dosene 0,4-0,8 mg effektivt og trygt

Nasal naloxone - A pilot study of the pharmacokinetics of a concentrated formulation

Introduction: Naloxone is the antidote against heroin and other opioids. As a measure to combat overdose deaths, nasal naloxone is wanted for bystander administration by lay people. The objective of this study was to investigate the pharmacokinetic profile of nasal naloxone delivered as in a high-concentration/low-volume formulation. The primary objective was to get a preliminary estimation of bioavailability of intranasal naloxone in human, healthy volunteers. Secondary objectives were a preliminary estimation of maximum serum concentration (Cmax) and time to maximum serum concentration (Tmax), and also to investigate the safety of the formulation. Materials and methods: This was a phase 1, single centre, open-label, randomised, two-way crossover trial in healthy male volunteers, n=5, age 18-45 years. 1.0 mg intravenous naloxone was compared to 2 mg intranasal naloxone given as 0.1 ml of 20 mg/ml nasal spray. Blood samples were drawn at predetermined intervals, and serum concentrations of naloxone was determined by a validated liquid chromatography-mass spectrometry method, and analysed by non-compartmental techniques. A 72-hour washout period was enforced between treatments. A post-study interview was performed. Results: Bioavailability (mean (95% confidence interval) were 47.1% (38.4-55.8) for the intranasal naloxone. Cmax were 4.24 (1.48-7.00). Tmax was reached after 16.0 min (5.80- 26.2). The mean half-lives varied from 80-90 min. No clinically significant adverse event was observed. Moreover, the spray provoked no unexpected adverse events. The only reported adverse drug reaction was taste of the nasal spray. Conclusions: The nasal sprayer resulted in a rapid systemic uptake, and a higher bioavailability than previously reported for low-concentration/high-volume formulations. The nasal spray provided serum concentration that surpassed the intravenous after 10 min, and stayed above until 240 min. The spray did not elicit worrying side effects in the exposed subjects. The results are promising and further development of the product is warranted. Based on these results we have chosen to study 8 and 16 mg/ml in the next study. Further trials comparing the nasal spray with clinically relevant doses of intramuscular naloxone, and studies investigating the pharmacodynamic properties of the product, is also needed

Neuroepidemiology of Konzo - a spastic para/tetraparesis of acute onset in a new area of the Democratic Republic of Congo

Background: Konzo is an acute non-progressive spastic paraparesis associated with a consumption of insufficiently processed bitter cassava, and a low intake of sulfur amino acids. Method: To determine whether an outbreak of spastic paraparesis in the Democratic Republic of Congo was compatible with konzo, we surveyed and screened the population in the affected area by using the WHO criteria. Interviews and focus group discussions were done on diet and the occurrence of konzo. Serum samples were analyzed for prealbumin, albumin and thiocyanate; urine samples for linamarin, thiocyanate and sulfate. Serum samples were tested for HIV 1-2 (Behring ELISA) and HTLV I-II antibodies (ELISA/Wellcome). Results: Of 2,723 inhabitants, 55 were affected by konzo i.e. a prevalence of 20 per thousand. The main symptom was a sudden onset of a non-progressive spastic paraparesis or a tetraparesis in severe cases. Bitter cassava was the staple diet. We found high exposure to cyanogenic compounds i.e., mean (± SD) concentration of serum thiocyanate 502 (±153) mmol/L, of urinary linamarin 482 (±322) mmol/L, and urinary thiocyanate 1128 (±670) mmol/L. The mean (± SD) urinary sulfate concentration was 4.0 ± 3.3 mmol/L. Most subjects had low proteins concentration in serum: of 38 subjects 37 and 28 were below the albumin and prealbumin reference values respectively. All 38 blood samples were negative to the tested retroviruses. Conclusion: This outbreak was compatible with konzo. Improving cassava processing might prevent the disease

Neuroepidemiology of Konzo a Spastic Para-Tetraparesis of Acute Onset in a New Area of the Democratic Republic of Congo (English)

Background Konzo is an acute non-progressive spastic paraparesis associated with a consumption of insufficiently processed bitter cassava, and a low intake of sulfur amino acids. Method To determine whether an outbreak of spastic paraparesis in the Democratic Republic of Congo was compatible with konzo, we surveyed and screened the population in the affected area by using the WHO criteria. Interviews and focus group discussions were done on diet and the occurrence of konzo. Serum samples were analyzed for prealbumin, albumin and thiocyanate; urine samples for linamarin, thiocyanate and sulfate. Serum samples were tested for HIV1-2 (Behring ELISA) and HTLV I-II antibodies (ELISA/Wellcome). Results Of 2,723 inhabitants, 55 were affected by konzo i.e. a prevalence of 20 per thousand. The main symptom was a sudden onset of a non-progressive spastic paraparesis or a tetraparesis in severe cases. Bitter cassava was the staple diet. We found high exposure to cyanogenic compounds i.e., mean (± SD) concentration of serum thiocyanate 502 (±153) mmol/L, of urinary linamarin 482 (±322) mmol/L, and urinary thiocyanate 1128 (±670) mmol/L. The mean (± SD) urinary sulfate concentration was 4.0 ± 3.3 mmol/L. Most subjects had low proteins concentration in serum: of 38 subjects 37 and 28 were below the albumin and prealbumin reference values respectively. All 38 blood samples were negative to the tested retroviruses. Conclusion This outbreak was compatible with konzo. Improving cassava processing might prevent the disease. Résumé  Description Le Konzo est une paraparésie spastique permanente, à début brutal, associée à la consommation de manioc insuffisamment traité avec une alimentation pauvre en acides aminés soufrés. Objectif Déterminer si une épidémie de paraparésie spastique en République Démocratique du Congo était compatible avec le konzo. Methode Un dépistage des cas de konzo a été effectué au moyen des critères de l\' OMS. Des interviews ont été réalisées sur l\'alimentation et la maladie. Les taux sériques de préalbumine, albumine et thiocyanate furent mesurés ainsi que ceux de linamarine, thiocyanate et sulfate dans les urines. Les serums furent testés pour HIV 1-2 (Behring ELISA) et HTLV I-II (ELISA/Wellcome). Resultats Sur 2.723 habitants, 55 étaient affectés par le konzo, soit une prévalence de 20 pour mille. Le symptôme majeur était une paraparésie spastique permanente à début brutal ou une tétraparésie dans les cas sévères, le manioc amer était l\'aliment de base. Il y avait une importante exposition aux substances cyanogénétiques: concentration moyenne (± écart-type) de thiocyanate sérique 502 (±153) mmol/L, de linamarine urinaire 482 (±322) mmol/L, de thiocyanate urinaire 1128 (±670) mmol/L. La concentration moyenne (± écart-type) de sulfate urinaire était 4.0 ± 3.3 mmol/L. En majorité, le taux des protéines sériques était en dessous de la normale: sur 38 sujets, 37 et 28 l\'avait pour l\'albumine et la préalbumine respectivement. Tous les 38 serums collectés étaient négatifs aux rétrovirus testés. Conclusion Cette épidémie était compatible avec le konzo. Ameliorer le traitement du manioc peut prevenir la maladie. Keywords: acute spastic paraparesis, cassava, cyanogens exposure, konzo, manioc, konzo, paraparésie spastique aigue, substances cyanogènes Af J Neuro Sci: 2001 20(1

Expanding the phenotypic spectrum of BCS1L-related mitochondrial disease

Publisher Copyright: © 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological AssociationObjective: To delineate the full phenotypic spectrum of BCS1L-related disease, provide better understanding of the genotype–phenotype correlations and identify reliable prognostic disease markers. Methods: We performed a retrospective multinational cohort study of previously unpublished patients followed in 15 centres from 10 countries. Patients with confirmed biallelic pathogenic BCS1L variants were considered eligible. Clinical, laboratory, neuroimaging and genetic data were analysed. Patients were stratified into different groups based on the age of disease onset, whether homozygous or compound heterozygous for the c.232A>G (p.Ser78Gly) variant, and those with other pathogenic BCS1L variants. Results: Thirty-three patients were included. We found that growth failure, lactic acidosis, tubulopathy, hepatopathy and early death were more frequent in those with disease onset within the first month of life. In those with onset after 1 month, neurological features including movement disorders and seizures were more frequent. Novel phenotypes, particularly involving movement disorder, were identified in this group. The presence of the c.232A>G (p.Ser78Gly) variant was associated with significantly worse survival and exclusively found in those with disease onset within the first month of life, whilst other pathogenic BCS1L variants were more frequent in those with later symptom onset. Interpretation: The phenotypic spectrum of BCS1L-related disease comprises a continuum of clinical features rather than a set of separate syndromic clinical identities. Age of onset defines BCS1L-related disease clinically and early presentation is associated with poor prognosis. Genotype correlates with phenotype in the presence of the c.232A>G (p.Ser78Gly) variant.Peer reviewe