PLACID study: A randomized trial comparing the efficacy and safety of inhaled loxapine versus intramuscular aripiprazole in acutely agitated patients with schizophrenia or bipolar disorder.

The aim of the study was to investigate the efficacy and safety of inhaled loxapine compared with the intramuscular (IM) antipsychotic aripiprazole in acutely agitated patients with schizophrenia or bipolar I disorder. PLACID was an assessor-blind, parallel-group trial conducted in 23 centres in the Czech Republic, Germany, Spain, and Russia. Patients (aged 18-65 years) diagnosed with schizophrenia or bipolar I disorder experiencing acute agitation (Clinical Global Impression [CGI]-Severity score ≥ 4) while hospitalized or attending an emergency room were randomized to receive up to two doses of inhaled loxapine 9.1 mg or IM aripiprazole 9.75 mg (≥ 2 h between doses) during the 24-h study period. The primary efficacy endpoint was time to response (CGI-Improvement score 1 [very much improved] or 2 [much improved]). The primary analysis included randomized patients who provided informed consent (full analysis set [FAS]); the safety analysis included all patients who received study medication. The FAS comprised 357 patients (enrolled December 2, 2014 - October 31, 2016). The between-treatment difference in median time to CGI-Improvement response was 10 min (95% CI 0.0-30.0); p = 0.0005) in favour of inhaled loxapine (median [95% CI]: 50 min [30.0-50.0] vs 60 min [50.0-90.0] with IM aripiprazole); the difference was significant at 10 min (responders: 14% [loxapine] vs 4% [aripiprazole]; p = 0.001). There were no safety issues. Inhaled loxapine reduced agitation faster than IM aripiprazole, supporting its use as a first-line option for managing acute agitation in patients with schizophrenia or bipolar disorder.

Health care and societal costs of the management of children and adolescents with attention-deficit/hyperactivity disorder in Spain: a descriptive analysis.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition in childhood (5.3% to 7.1% worldwide prevalence), with substantial overall financial burden to children/adolescents, their families, and society. The aims of this study were to describe the clinical characteristics of children and adolescents with ADHD in Spain, estimate the associated direct/indirect costs of the disorder, and assess whether the characteristics and financial costs differed between children/adolescents adequately responding to currently available pharmacotherapies compared with children/adolescents for whom pharmacotherapies failed. METHODS: This was a multicenter, cross-sectional, descriptive analysis conducted in 15 health units representative of the overall Spanish population. Data on demographic characteristics, socio-occupational status, social relationships, clinical variables of the disease, and pharmacological and non-pharmacological treatments received were collected in 321 children and adolescents with ADHD. Direct and indirect costs were estimated over one year from both a health care system and a societal perspective. RESULTS: The estimated average cost of ADHD per year per child/adolescent was €5733 in 2012 prices; direct costs accounted for 60.2% of the total costs (€3450). Support from a psychologist/educational psychologist represented 45.2% of direct costs and 27.2% of total costs. Pharmacotherapy accounted for 25.8% of direct costs and 15.5% of total costs. Among indirect costs (€2283), 65.2% was due to caregiver expenses. The total annual costs were significantly higher for children/adolescents who responded poorly to pharmacological treatment (€7654 versus €5517; P = 0.024), the difference being mainly due to significantly higher direct costs, particularly with larger expenses for non-pharmacological treatment (P = 0.012). CONCLUSIONS: ADHD has a significant personal, familial, and financial impact on the Spanish health system and society. Successful pharmacological intervention was associated with lower overall expenses in the management of the disorder.

Efecto del condroitín sulfato en la sinovitis de pacientes con artrosis de rodilla / Effect of chondroitin sulphate on synovitis of knee osteoarthritic patients

Objetivo: Evaluar mediante ecografía el efecto del condroitín sulfato (CS) en la sinovitis de pacientes con artrosis (OA) de rodilla, y colaborar en el conocimiento de los mecanismos bioquímicos involucrados en la inflamación sinovial. Métodos: Estudio controlado, aleatorizado, ciego simple de 70 pacientes con OA de rodilla tratados durante 6 meses con CS o paracetamol (PCT). Los pacientes fueron visitados a tiempo basal, a las 6 semanas, y a los 3 y 6 meses para valorar el estado de su OA según los siguientes parámetros: sinovitis evaluada mediante ecografía (según definición de expertos OMERACT); dolor y función, mediante la escala visual analógica y el índice de Lequesne; y concentración de mediadores inflamatorios en suero y líquido sinovial, mediante ELISA. Resultados: El tratamiento con CS redujo en un 50% el número de individuos que presentaban sinovitis; sin embargo, se observó un incremento de un 123% en el grupo tratado con PCT. En los pacientes sin sinovitis inicial, se observó el establecimiento de esta en un 85,71 y 25% de los casos tratados con PCT y CS, respectivamente. Ambas terapias mejoraron la función articular, pero únicamente el tratamiento con CS produjo una mejora significativa del dolor al final del tratamiento. Se observó una asociación entre el tratamiento con CS y los cambios en la concentración de RANTES y UCN en el líquido sinovial. Conclusiones: El tratamiento con CS tiene un efecto mantenido beneficioso, previniendo la aparición de sinovitis o disminuyendo su presencia, así como reduciendo los síntomas de la artrosis. El PCT también mejora los síntomas clínicos, pero no tiene ningún efecto sobre la inflamación. Las variaciones observadas en la concentración de RANTES y UCN podrían estar relacionadas con el efecto antiinflamatorio asociado al tratamiento con CS (AU)

Objective: To evaluate by ultrasonography the effect of chondroitin sulfate (CS) on synovitis in patients with knee osteoarthritis (KOA). To collaborate in the understanding of the biochemical mechanisms involved in the synovial inflammation process. Methods: Randomized, single-blind, controlled trial involving 70 patients with primary KOA treated for 6 months with CS or acetaminophen (ACT). Evaluation of KOA status at baseline, 6 weeks, 3 and 6 months included: ultrasonography to assess synovitis (following the OMERACT expertise group definition), visual analogue scale and Lequesne index to measure pain and function, and ELISA to quantify inflammatory mediators in serum and synovial fluid. Results: Synovitis presence was reduced by 50% in the CS group while a 123% increase was observed in ACT group. Conversely, patients without initial synovitis and treated with ACT reached 85.71% synovitis onset, but only 25% in CS group. Both therapies improved articular function, but only CS resulted in significant pain improvement at the end of the treatment. Changes in RANTES and UCN synovial fluid concentration were associated with CS treatment. Conclusions: Treatment with CS had a sustained beneficial effect, preventing synovitis onset or reducing its presence as well as reducing KOA symptoms. ACT ameliorated clinical symptoms but had no effect on inflammation. The CS anti-inflammatory effect could be related to the observed changes in RANTES and UCN concentration (AU)

Efectos del condroitín sulfato sobre la respuesta cerebral a la estimulación dolorosa en pacientes con artrosis de rodilla. Estudio de resonancia magnética funcional aleatorizado, doble ciego y controlado con placebo / Effects of chondroitin sulfate on brain response to painful stimulation in knee osteoarthritis patients. A randomized, double-blind, placebo-controlled functional magnetic resonance imaging study

Introducción: La artrosis de rodilla es causa de dolor e incapacidad funcional. Uno de los problemas para evaluar la eficacia de los analgésicos ha sido la falta de medidas objetivas de dolor, aunque la resonancia magnética funcional (RMf) ha surgido como un medio útil para objetivar la respuesta del cerebro a la estimulación dolorosa. Hemos investigado el efecto del condroitín sulfato (CS) sobre la respuesta del cerebro a la estimulación dolorosa de la rodilla en pacientes con artrosis mediante RMf. Métodos: Veintidós pacientes recibieron CS (800mg/día) y 27 placebo y fueron evaluados inicialmente y después de 4 meses de tratamiento. En cada sesión de RMf se aplicó presión dolorosa sobre la interlínea de la rodilla y en la superficie de la rótula. El resultado se cuantificó como la atenuación de la respuesta cerebral a la estimulación dolorosa de la rodilla. Resultados: La RMf de la maniobra rotuliana mostró una reducción de la activación en la región de la sustancia gris periacueductal del mesencéfalo significativamente mayor durante el tratamiento con CS que en la condición de placebo. El grupo de CS, pero no el de placebo, mostró además una reducción de la activación en la representación cortical de la pierna tras el tratamiento. No se observaron efectos del CS con presión dolorosa sobre la interlínea de la rodilla. Conclusiones: La RMf fue sensible para objetivar los efectos del CS sobre la respuesta del cerebro a la presión dolorosa sobre el cartílago rotuliano-femoral, que es un resultado coherente con la acción conocida del CS sobre la regeneración de los condrocitos. El presente trabajo muestra nuevamente la utilidad de la RMf para objetivar los efectos del tratamiento en el dolor de origen artrósico (AU)

Introduction: Knee osteoarthritis is causing pain and functional disability. One of the inherent problems with efficacy assessment of pain medication was the lack of objective pain measurements, but functional magnetic resonance imaging (fMRI) has emerged as a useful means to objectify brain response to painful stimulation. We have investigated the effect of chondroitin sulfate (CS) on brain response to knee painful stimulation in patients with knee osteoarthritis using fMRI. Methods: Twenty-two patients received CS (800mg/day) and 27 patients placebo, and were assessed at baseline and after 4 months of treatment. Two fMRI tests were conducted in each session by applying painful pressure on the knee interline and on the patella surface. The outcome measurement was attenuation of the response evoked by knee painful stimulation in the brain. Results: fMRI of patella pain showed significantly greater activation reduction under CS compared with placebo in the region of the mesencephalic periaquecductal gray. The CS group, additionally showed pre/post-treatment activation reduction in the cortical representation of the leg. No effects of CS were detected using the interline pressure test. Conclusions: fMRI was sensitive to objectify CS effects on brain response to painful pressure on patellofemoral cartilage, which is consistent with the known CS action on chondrocyte regeneration. The current work yields further support to the utility of fMRI to objectify treatment effects on osteoarthritis pain (AU)

Effect of chondroitin sulphate on synovitis of knee osteoarthritic patients. / Efecto del condroitín sulfato en la sinovitis de pacientes con artrosis de rodilla.

OBJECTIVE: To evaluate by ultrasonography the effect of chondroitin sulfate (CS) on synovitis in patients with knee osteoarthritis (KOA). To collaborate in the understanding of the biochemical mechanisms involved in the synovial inflammation process. METHODS: Randomized, single-blind, controlled trial involving 70 patients with primary KOA treated for 6 months with CS or acetaminophen (ACT). Evaluation of KOA status at baseline, 6 weeks, 3 and 6 months included: ultrasonography to assess synovitis (following the OMERACT expertise group definition), visual analogue scale and Lequesne index to measure pain and function, and ELISA to quantify inflammatory mediators in serum and synovial fluid. RESULTS: Synovitis presence was reduced by 50% in the CS group while a 123% increase was observed in ACT group. Conversely, patients without initial synovitis and treated with ACT reached 85.71% synovitis onset, but only 25% in CS group. Both therapies improved articular function, but only CS resulted in significant pain improvement at the end of the treatment. Changes in RANTES and UCN synovial fluid concentration were associated with CS treatment. CONCLUSIONS: Treatment with CS had a sustained beneficial effect, preventing synovitis onset or reducing its presence as well as reducing KOA symptoms. ACT ameliorated clinical symptoms but had no effect on inflammation. The CS anti-inflammatory effect could be related to the observed changes in RANTES and UCN concentration.

Effects of chondroitin sulfate on brain response to painful stimulation in knee osteoarthritis patients. A randomized, double-blind, placebo-controlled functional magnetic resonance imaging study. / Efectos del condroitín sulfato sobre la respuesta cerebral a la estimulación dolorosa en pacientes con artrosis de rodilla. Estudio de resonancia magnética funcional aleatorizado, doble ciego y controlado con placebo.

INTRODUCTION: Knee osteoarthritis is causing pain and functional disability. One of the inherent problems with efficacy assessment of pain medication was the lack of objective pain measurements, but functional magnetic resonance imaging (fMRI) has emerged as a useful means to objectify brain response to painful stimulation. We have investigated the effect of chondroitin sulfate (CS) on brain response to knee painful stimulation in patients with knee osteoarthritis using fMRI. METHODS: Twenty-two patients received CS (800mg/day) and 27 patients placebo, and were assessed at baseline and after 4 months of treatment. Two fMRI tests were conducted in each session by applying painful pressure on the knee interline and on the patella surface. The outcome measurement was attenuation of the response evoked by knee painful stimulation in the brain. RESULTS: fMRI of patella pain showed significantly greater activation reduction under CS compared with placebo in the region of the mesencephalic periaquecductal gray. The CS group, additionally showed pre/post-treatment activation reduction in the cortical representation of the leg. No effects of CS were detected using the interline pressure test. CONCLUSIONS: fMRI was sensitive to objectify CS effects on brain response to painful pressure on patellofemoral cartilage, which is consistent with the known CS action on chondrocyte regeneration. The current work yields further support to the utility of fMRI to objectify treatment effects on osteoarthritis pain.

Comparative efficacy of intra-articular hyaluronic acid and corticoid injections in osteoarthritis of the first carpometacarpal joint: results of a 6-month single-masked randomized study.

OBJECTIVE: The study aim was to compare the efficacy and safety of ultrasound-guided intra-articular injections of hyaluronic acid and betamethasone in the management of patients with osteoarthritis of the thumb. METHODS: Eighty-eight evaluable patients diagnosed with osteoarthritis of the thumb (Kellgren-Lawrence grade II-III) received ultrasound-guided intra-articular treatment with hyaluronic acid (48) or betamethasone (40). In total, 3 local injections were scheduled at 7-day intervals. Assessments were performed at baseline and at 7, 14, 30, 90, and 180 days. RESULTS: In both study groups, the pain Visual Analogue Scale and Functional Index for Hand Osteoarthritis scores decreased significantly during follow-up compared to baseline. There were no significant differences between the groups. However, at 90 days, the functional score showed a trend towards greater clinical improvement in the hyaluronic acid group (P 0.071). A subanalysis of patients with Functional Index score≥5 and Visual Analogue Scale score≥3 at baseline showed a significantly higher median functionality score in the hyaluronic acid group (P 0.005 at 90 days and P 0.020 at 180 days). Further limiting analysis to a baseline pain score≥5 showed significantly greater improvement in functionality score (P 0.004 at 180 days), which was already apparent after the second intra-articular injection at 14 days (P 0.028). In this patient subset, the mean pain score also improved significantly at 180 days (P 0.02). CONCLUSIONS: Both hyaluronic acid and betamethasone were effective and well-tolerated for the management of rhizarthrosis. Hyaluronic acid was more effective over time and more efficiently improved functionality and pain in patients with more severe symptoms.

Treating enuresis in a patient with ADHD: application of a novel behavioural modification therapy.

We report the case of a 6-year-old patient diagnosed with attention-deficit hyperactivity disorder (ADHD) and comorbid enuresis disorder, who was treated with methylphenidate for the past 3 months and a novel behavioural modification therapy by using an application called 'Enuresis Trainer'. This therapeutic application is basically an interactive 'Bedwetting Calendar', based on traditional cognitive behavioural modification therapies and positive reinforcement systems. Enuresis is defined as the failure of voluntary control of the urethral sphincter. The prevalence of enuresis is 15-20% in the child population; however, children with ADHD had a 2.7 times higher incidence of nocturnal enuresis. Bedwetting is a common cause of isolation in children as well as loss of self-esteem and other psychological distress for the child and the family.