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Anti-drug antibodies (ADA) reduce the efficacy of immunotherapies in multiple sclerosis (MS) and are associated with increased disease progression risk. Blood biomarkers predicting immunogenicity to biopharmaceuticals represent an unmet clinical need. Patients with relapsing remitting (RR)MS were recruited before (baseline), three, and 12 (M12) months after commencing interferon-beta treatment. Neutralising ADA-status was determined at M12, and patients were stratified at baseline according to their M12 ADA-status (ADA-positive/ADA-negative). Patients stratified as ADA-positive were characterised by an early dampened response to interferon-beta (prior to serum ADA detection) and distinct proinflammatory transcriptomic/proteomic peripheral blood signatures enriched for 'immune response activation' including phosphoinositide 3-kinase-γ and NFκB-signalling pathways both at baseline and throughout the treatment course, compared to ADA-negative patients. These immunogenicity-associated proinflammatory signatures significantly overlapped with signatures of MS disease severity. Thus, whole blood molecular profiling is a promising tool for prediction of ADA-development in RRMS and could provide insight into mechanisms of immunogenicity.
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Interferón beta , Esclerosis Múltiple Recurrente-Remitente , Proteómica , Transcriptoma , Humanos , Interferón beta/uso terapéutico , Interferón beta/inmunología , Femenino , Masculino , Adulto , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/inmunología , Esclerosis Múltiple Recurrente-Remitente/sangre , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Biomarcadores/sangre , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/sangreRESUMEN
Altered cholesterol, oxysterol, sphingolipid, and fatty acid concentrations are reported in blood, cerebrospinal fluid, and brain tissue of people with relapsing-remitting multiple sclerosis (RRMS) and are linked to disease progression and treatment responses. CD4â +â T cells are pathogenic in RRMS, and defective T-cell function could be mediated in part by liver X receptors (LXRs)-nuclear receptors that regulate lipid homeostasis and immunity. RNA-sequencing and pathway analysis identified that genes within the 'lipid metabolism' and 'signalling of nuclear receptors' pathways were dysregulated in CD4â +â T cells isolated from RRMS patients compared with healthy donors. While LXRB and genes associated with cholesterol metabolism were upregulated, other T-cell LXR-target genes, including genes involved in cellular lipid uptake (inducible degrader of the LDL receptor, IDOL), and the rate-limiting enzyme for glycosphingolipid biosynthesis (UDP-glucosylceramide synthase, UGCG) were downregulated in T cells from patients with RRMS compared to healthy donors. Correspondingly, plasma membrane glycosphingolipids were reduced, and cholesterol levels increased in RRMS CD4â +â T cells, an effect partially recapitulated in healthy T cells by in vitro culture with T-cell receptor stimulation in the presence of serum from RRMS patients. Notably, stimulation with LXR-agonist GW3965 normalized membrane cholesterol levels, and reduced proliferation and IL17 cytokine production in RRMS CD4â +â T-cells. Thus, LXR-mediated lipid metabolism pathways were dysregulated in T cells from patients with RRMS and could contribute to RRMS pathogenesis. Therapies that modify lipid metabolism could help restore immune cell function.
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Linfocitos T CD4-Positivos , Metabolismo de los Lípidos , Receptores X del Hígado , Esclerosis Múltiple Recurrente-Remitente , Humanos , Esclerosis Múltiple Recurrente-Remitente/inmunología , Esclerosis Múltiple Recurrente-Remitente/metabolismo , Receptores X del Hígado/metabolismo , Femenino , Adulto , Masculino , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Persona de Mediana Edad , Colesterol/metabolismo , Glicoesfingolípidos/metabolismoRESUMEN
BACKGROUND: Research on cognitive rehabilitation (CR) and aerobic exercise (EX) to improve cognition in progressive multiple sclerosis (PMS) remains limited. CogEx trial investigated the effectiveness of CR and EX in PMS: here, we present MRI substudy volumetric and task-related functional MRI (fMRI) findings. METHODS: Participants were randomised to: 'CR plus EX', 'CR plus sham EX (EX-S)', 'EX plus sham CR (CR-S)' and 'CR-S plus EX-S' and attended 12-week intervention. All subjects performed physical/cognitive assessments at baseline, week 12 and 6 months post intervention (month 9). All MRI substudy participants underwent volumetric MRI and fMRI (Go-NoGo task). RESULTS: 104 PMS enrolled at four sites participated in the CogEx MRI substudy; 84 (81%) had valid volumetric MRI and valid fMRI. Week 12/month 9 cognitive performances did not differ among interventions; however, 25-62% of the patients showed Symbol Digit Modalities Test improvements. Normalised cortical grey matter volume (NcGMV) changes at week 12 versus baseline were heterogeneous among interventions (p=0.05); this was mainly driven by increased NcGMV in 'CR plus EX-S' (p=0.02). Groups performing CR (ie, 'CR plus EX' and 'CR plus EX-S') exhibited increased NcGMV over time, especially in the frontal (p=0.01), parietal (p=0.04) and temporal (p=0.04) lobes, while those performing CR-S exhibited NcGMV decrease (p=0.008). In CR groups, increased NcGMV (r=0.36, p=0.01) at week 12 versus baseline correlated with increased California Verbal Learning Test (CVLT)-II scores. 'CR plus EX-S' patients exhibited Go-NoGo activity increase (p<0.05, corrected) at week 12 versus baseline in bilateral insula. CONCLUSIONS: In PMS, CR modulated grey matter (GM) volume and insular activity. The association of GM and CVLT-II changes suggests GM plasticity contributes to cognitive improvements. TRIAL REGISTRATION NUMBER: NCT03679468.
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OBJECTIVE: Literature on trainee clinical psychologists' mental health has highlighted elevated levels of mental health difficulties and/or psychological distress and low levels of disclosure within the workplace. The current study aimed to explore (1) trainee experiences of disclosure and/or concealment of psychological distress during their training, (2) beliefs, assumptions or predictions related to disclosure and (3) responses to disclosure. METHODS: A mixed-methods strategy was employed; 165 trainee or recently qualified clinical psychologists took part in an online survey. Thirteen of these were interviewed. Descriptive statistics and a reflexive thematic analysis were conducted to analyse the quantitative and qualitative data, respectively. RESULTS: The sample largely consisted of those who had disclosed distress. Beliefs related to negative judgement from others and feelings of anxiety and embarrassment were commonly endorsed responses within quantitative findings. Six main themes were constructed: (1) Diagnostic or psychological conceptualisations, (2) Worries about judgement complicate disclosure decisions, (3) Disclosure likelihood is determined by relationships, (4) Emotional support versus practical responses, (5) Desired changes that could increase disclosure and (6) Legacies of disclosure experiences. CONCLUSION: There is a need for training programme staff to prioritise emotional support, increase permission giving and enhance disclosure guidance. Further research including disclosure recipients is required.
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Shoulder pain is common after neurological injury and can be disabling, lead to poor functional outcomes and increase care costs. Its cause is multifactoral and several pathologies contribute to the presentation. Astute diagnostic skills and a multidisciplinary approach are required to recognise what is clinically relevant and to implement appropriate stepwise management. In the absence of large clinical trial data, we aim to provide a comprehensive, practical and pragmatic overview of shoulder pain in patients with neurological conditions. We use available evidence to produce a management guideline, taking into account specialty opinions from neurology, rehabilitation medicine, orthopaedics and physiotherapy.
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Dolor de Hombro , Accidente Cerebrovascular , Humanos , Hemiplejía/etiología , Hemiplejía/rehabilitación , Manejo del Dolor , Dolor de Hombro/diagnóstico , Dolor de Hombro/etiología , Dolor de Hombro/terapia , Accidente Cerebrovascular/complicacionesRESUMEN
OBJECTIVE: Processing speed (PS) deficits are the most common cognitive deficits in multiple sclerosis (MS), followed by learning and memory deficits, and are often an early cognitive problem. It has been argued that impaired PS is a primary consequence of MS, which in turn decreases learning. The current analysis examined the association between PS and learning in a large cohort of individuals with progressive MS. METHODS: Baseline data from a randomized clinical trial on rehabilitation taking place at 11 centers across North America and Europe were analyzed. Participants included 275 individuals with clinically definite progressive MS (primary, secondary) consented into the trial. RESULTS: Symbol Digit Modalities Test (SDMT) significantly correlated with California Verbal Learning Test-II (CVLT-II) (r = 0.21, p = 0.0003) and Brief Visuospatial Memory Test-Revised (BVMT-R) (r = 0.516, p < 0.0001). Receiver operating characteristic (ROC) analysis of the SDMT z score to distinguish between impaired and non-impaired CVLT-II performance demonstrated an area under the curve (AUC) of 0.61 (95% confidence interval (CI): 0.55-0.68) and a threshold of -1.62. ROC analysis between SDMT and BVMT-R resulted in an AUC of 0.77 (95% CI: 0.71-0.83) and threshold of -1.75 for the SDMT z score to predict impaired BVMT-R. CONCLUSION: Results indicate little ability beyond chance to predict CVLT-II from SDMT (61%), albeit statistically significant. In contrast, there was a 77% chance that the model could distinguish between impaired and non-impaired BVMT-R. Several potential explanations are discussed.
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Trastornos del Conocimiento , Esclerosis Múltiple Crónica Progresiva , Esclerosis Múltiple , Cognición , Trastornos del Conocimiento/complicaciones , Humanos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/psicología , Esclerosis Múltiple Crónica Progresiva/complicaciones , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: Aerobic exercise training (physical activity for improving cardiorespiratory fitness) represents a promising approach for managing cognitive impairment in multiple sclerosis (MS). However, there is limited evidence that levels of physical activity and fitness are associated with cognition in progressive MS. OBJECTIVE: We examined associations among cardiorespiratory fitness, moderate-to-vigorous physical activity (MVPA), and cognitive performance in a large, international progressive MS sample. METHODS: Two hundred forty European and North American persons with progressive MS underwent cardiorespiratory fitness measurement on a recumbent stepper, wore an ActiGraph GT3X + accelerometer for 7 days for measuring MVPA, and underwent the Brief International Cognitive Assessment in MS. RESULTS: Cardiorespiratory fitness was not significantly correlated with Symbol Digit Modalities Test (SDMT; r = -0.01; r = -0.04), California Verbal Learning Test-II (CVLT-II; r = 0.05; r = 0.05), or Brief Visuospatial Memory Test-Revised (BVMT-R; r = -0.14; r = -0.14) z-scores controlling for age, sex, and education. MVPA and SDMT (r = 0.05), CVLT-II (r = -0.07), and BVMT-R (r = 0.01) z-scores were not significantly correlated. CONCLUSION: Cardiorespiratory fitness and MVPA were not associated with cognition in this large progressive MS sample, yet these outcomes represent critical manipulation checks for documenting the success of the CogEx trial. This highlights the importance of examining other exercise-related mechanisms-of-action for improving cognition in progressive MS.
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Capacidad Cardiovascular , Esclerosis Múltiple Crónica Progresiva , Esclerosis Múltiple , Cognición , Ejercicio Físico , Humanos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/psicología , Esclerosis Múltiple Crónica Progresiva/complicaciones , Pruebas Neuropsicológicas , Aptitud FísicaRESUMEN
OBJECTIVE: To systematically review evidence regarding prevalence and choices of disclosure of psychological distress, by mental health professionals within the workplace. METHODS: Six databases were searched in June 2020. Studies were included if they were published in English language and included empirical quantitative, qualitative or mixed-methods data. Studies were excluded if they focused on general healthcare professionals or the general population, or on stress or physical health problems. Study quality was assessed using the Mixed Methods Quality Appraisal tool. RESULTS: Nine studies, with a total of 1891 participants, were included. Study quality varied, with studies generally reporting descriptive surveys using hypothetical disclosure scenarios. Distress was often conceptualized in psychiatric terms. These limitations mean conclusions should be treated with caution. Individuals were less likely to disclose in work and had negative experiences of doing so compared to social circles. Fear of stigma inhibited disclosure. There were differing levels of disclosure relating to recipient, trust, quality of supervision, how distress was conceptualized, and type of problem. Disclosure was experienced by some as valuable. CONCLUSION: There is a need for further research, which addresses the nuanced complexities surrounding disclosure choices for mental health professionals.
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Distrés Psicológico , Lugar de Trabajo , Revelación , Personal de Salud , Humanos , Salud Mental , Lugar de Trabajo/psicologíaRESUMEN
OBJECTIVES AND DESIGN: Debate exists as to patient experience, and the importance, of the working alliance (WA) in videoconferencing psychotherapy (VCP). This study used a two-phase explanatory sequential design to investigate the WA as a change process in VCP. METHODS: Phase I: sessional VCP outcome and WA data were analysed using multilevel modelling (n = 46). Phase II: participants (n = 12) from Phase I were recruited to semi-structured interviews, analysed using thematic framework analysis. RESULTS AND CONCLUSIONS: Results demonstrate: (1) a significant correlation between WA and outcome (F(1, 15.19) = 25.01, p < 0.001), (2) previous session WA significantly predicted outcome in the next session (F(1, 355.61) = 4.47, p < 0.05), and (3) previous session outcome significantly predicted next session WA (F(1, 55.3) = 15.19, p < 0.001), with three core themes explaining patient experience (engaging with the medium, connection with the therapist, and working via the medium). Results are discussed and future research recommended.
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Relaciones Profesional-Paciente , Psicoterapia , Humanos , Comunicación por VideoconferenciaRESUMEN
OBJECTIVES: Intrathecal baclofen (ITB) pumps are an effective treatment for spasticity; however infection rates have been reported in 3-26% of patients in the literature. The multidisciplinary ITB service has been established at The National Hospital for Neurology and Neurosurgery, UCLH, Queen Square, London for over 20 years. Our study was designed to clarify the rate of infection in our ITB patient cohort and secondly, to formulate and implement best practice guidelines and to determine prospectively, whether they effectively reduced infection rates. METHODS: Clinical record review of all patients receiving ITB pre-intervention; January 2013-May 2015, and following practice changes; June 2016-June 2018. RESULTS: Four of 118 patients receiving ITB during the first time period (3.4%, annual incidence rate of infection 1.4%) developed an ITB-related infection (three following ITB pump replacement surgery, one after initial implant). Infections were associated with 4.2% of ITB-related surgical procedures. Three of four pumps required explantation. Following change in practice (pre-operative chlorhexidine skin wash and intraoperative vancomycin wash of the fibrous pocket of the replacement site), only one of 160 ITB patients developed infection (pump not explanted) in the second time period (0.6%, annual incidence rate 0.3%). The infection rate related to ITB surgical procedures was 1.1%. In cases of ITB pump replacement, the infection rate was reduced to 3.3% from 17.6%. CONCLUSIONS: This study suggests that a straightforward change in clinical practice may lower infection rates in patients undergoing ITB therapy.
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Baclofeno , Infecciones , Bombas de Infusión Implantables/efectos adversos , Inyecciones Espinales , Relajantes Musculares Centrales , Espasticidad Muscular , Baclofeno/efectos adversos , Humanos , Infecciones/etiología , Relajantes Musculares Centrales/efectos adversos , Espasticidad Muscular/tratamiento farmacológico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Videoconferencing psychotherapy (VCP)-the remote delivery of psychotherapy via secure video link-is an innovative way of delivering psychotherapy, which has the potential to overcome many of the regularly cited barriers to accessing psychological treatment. However, some debate exists as to whether an adequate working alliance can be formed between therapist and client, when therapy is delivered through such a medium. The presented article is a systematic literature review and two meta-analyses aimed at answering the questions: Is working alliance actually poorer in VCP? And is outcome equivalence possible between VCP and face-to-face delivery? Twelve studies were identified which met inclusion/exclusion criteria, all of which demonstrated good working alliance and outcome for VCP. Meta-analyses showed that working alliance in VCP was inferior to face-to-face delivery (standardized mean difference [SMD] = -0.30; 95% confidence interval [CI] [-0.67, 0.07], p = 0.11; with the lower bound of the CI extending beyond the noninferiority margin [-0.50]), but that target symptom reduction was noninferior (SMD = -0.03; 95% CI [-0.45, 0.40], p = 0.90; CI within the noninferiority margin [0.50]). These results are discussed and directions for future research recommended.
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Trastornos Mentales/terapia , Relaciones Profesional-Paciente , Psicoterapia/métodos , Telemedicina/métodos , Comunicación por Videoconferencia , Humanos , Resultado del TratamientoRESUMEN
OBJECTIVES: The study investigated the relationship between exposure to trauma work and well-being (general psychological distress, trauma symptoms, and disrupted beliefs) in trainee clinical psychologists. It also assessed the contribution of individual and situational factors to well-being. DESIGN: A Web-based survey was employed. METHODS: The survey comprised the General Health Questionnaire, Secondary Traumatic Stress Scale, Trauma and Attachment Belief Scale, Trauma Screening Questionnaire, and specific questions about exposure to trauma work and other individual and situational factors. The link to the online survey was sent via email to trainee clinical psychologists attending courses throughout the UK RESULTS: Five hundred sixty-four trainee clinical psychologists participated. Most trainees had a caseload of one to two trauma cases in the previous 6 months; the most common trauma being sexual abuse. Exposure to trauma work was not related to general psychological distress or disrupted beliefs but was a significant predictor of trauma symptoms. Situational factors contributed to the variance in trauma symptoms; level of stress of clinical work and quality of trauma training were significant predictors of trauma symptoms. Individual and situational factors were also found to be significant predictors of general psychological distress and disrupted beliefs. CONCLUSIONS: This study provides support for secondary traumatic stress but lacks evidence to support belief changes in vicarious traumatization or a relationship between exposure to trauma work and general psychological distress. The measurement and validity of vicarious traumatization is discussed along with clinical, theoretical implications, and suggestions for future research. PRACTITIONER POINTS: Secondary traumatic stress is a potential risk for trainee clinical psychologists. Training courses should (a) focus on quality of trauma training as it may be protective; (b) advocate coping strategies to reduce stress of clinical work, as the level of stress of clinical work may contribute to trauma symptoms. LIMITATIONS INCLUDE: Exposure to trauma work only uniquely explained a small proportion of variance in trauma symptoms. The study was cross-sectional in nature therefore cannot imply causality.
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Actitud del Personal de Salud , Psicología/educación , Estrés Psicológico/psicología , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Encuestas y Cuestionarios , Reino UnidoRESUMEN
OBJECTIVE: To assess biochemical, surgical, and long-term outcomes of liver (LT) or liver-kidney transplantation (LKT) for severe, early-onset methylmalonic acidemia/acid (MMA). STUDY DESIGN: A retrospective chart review (December 1997 to May 2012) of patients with MMA who underwent LT or LKT at Lucile Packard Children's Hospital at Stanford. RESULTS: Fourteen patients underwent LT (n = 6) or LKT (n = 8) at mean age 8.2 years (range 0.8-20.7). Eleven (79%) were diagnosed during the neonatal period, including 6 by newborn screening. All underwent deceased donor transplantation; 12 (86%) received a whole liver graft. Postoperative survival was 100%. At a mean follow-up of 3.25 ± 4.2 years, patient survival was 100%, liver allograft survival 93%, and kidney allograft survival 100%. One patient underwent liver re-transplantation because of hepatic artery thrombosis. After transplantation, there were no episodes of hyperammonemia, acidosis, or metabolic decompensation. The mean serum MMA at the time of transplantation was 1648 ± 1492 µmol/L (normal <0.3, range 99-4420). By 3 days, post-transplantation levels fell on average by 87% (mean 210 ± 154 µmol/L), and at 4 months, they were 83% below pre-transplantation levels (mean 305 ± 108 µmol/L). Developmental delay was present in 12 patients (86%) before transplantation. All patients maintained neurodevelopmental abilities or exhibited improvements in motor skills, learning abilities, and social functioning. CONCLUSIONS: LT or LKT for MMA eradicates episodes of hyperammonemia, results in excellent long-term survival, and suggests stabilization of neurocognitive development. Long-term follow-up is underway to evaluate whether patients who undergo early LT need kidney transplantation later in life.
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Errores Innatos del Metabolismo de los Aminoácidos/cirugía , Trasplante de Riñón , Trasplante de Hígado , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: The aim of this study is to assess Latina patient understanding of noninvasive prenatal testing (NIPT) and identify what factors influence uptake/refusal to NIPT to adapt counseling to the needs and interests of this population. METHODS: Mixed-methods survey in English and Spanish administered to pregnant Latina patients throughout pregnancy. RESULTS: Sixty-three women participated in our study (67% response rate); 34.9% chose to do NIPT, and 65.1% declined. Approximately half of participants (44%) had an NIPT knowledge score of ≤3 out of six total questions. Two of the most significant factors influencing uptake of NIPT were a higher reported educational level (p = 0.015) and a higher NIPT knowledge score (p = 0.014); 42.9% of participants knew that NIPT only screens for certain chromosomal conditions; 39% of women who declined NIPT would never consider NIPT in the future. CONCLUSIONS: One-third of Latina women elected NIPT; a higher reported educational level and language were most predictive of this choice. Overall knowledge was significantly lower for women who declined NIPT. Lower knowledge may suggest that not all women are making informed decisions because of varying degrees of informed consent. Providing culturally tailored information can help women navigate the complexities of prenatal testing in order to make decisions most aligned with their values.
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Conocimientos, Actitudes y Práctica en Salud/etnología , Hispánicos o Latinos , Pruebas de Detección del Suero Materno/estadística & datos numéricos , Aceptación de la Atención de Salud/etnología , Adolescente , Adulto , California , Escolaridad , Femenino , Encuestas de Atención de la Salud , Hispánicos o Latinos/psicología , Humanos , Consentimiento Informado , Lenguaje , Modelos Lineales , Pruebas de Detección del Suero Materno/psicología , Aceptación de la Atención de Salud/psicología , Aceptación de la Atención de Salud/estadística & datos numéricos , Embarazo , Investigación Cualitativa , Adulto JovenRESUMEN
BACKGROUND: Spasticity is a common and potentially debilitating symptom of multiple sclerosis (MS) with a highly variable presentation. Understanding, quantifying, and managing MS-associated spasticity (MSS) is a challenge for research and in clinical practice. The tetrahydrocannabinol:cannabidiol oromucosal spray nabiximols has demonstrated beneficial effects in the treatment of MSS in clinical studies as well as real-world observational studies, and is approved for the treatment of MSS in 29 countries globally. Most randomized studies evaluated the efficacy of nabiximols using the change in average daily spasticity scores reported by patients using the spasticity Numeric Rating Scale as a primary endpoint. This study, RELEASE MSS1 (NCT04657666), was conducted using a prespecified primary endpoint of change in spastic muscle tone (Modified Ashworth Scale Lower Limb Muscle Tone-6 [MAS LLMT-6]) to corroborate the efficacy of nabiximols as adjunctive therapy observed with the patient-measured spasticity Numeric Rating Scale primary endpoint in the previous pivotal studies. METHODS: This was a phase 3, multicenter, randomized, double-blind, placebo-controlled, 2-treatment, 2-period, crossover trial. Because of the prevalence and functional impact of lower limb spasticity on the individual patient's overall experience of MS spasticity, the MAS LLMT-6 was derived from the clinician-rated MAS. The MAS LLMT-6 is the average transformed MAS score of 6 muscle groups (knee flexors, knee extensors, and ankle plantar flexors; all assessed bilaterally). Secondary measures included MAS LLMT-4 scores, defined as the average of the 4 individual MAS-transformed scores of knee flexors and knee extensors bilaterally. Patients had a diagnosis of MS and an untransformed MAS score of at least 2 in ≥2 of 6 LLMT-6 muscle groups despite current treatment with ≥1 of the following oral antispasticity agents: baclofen, tizanidine, or dantrolene. Eligible participants were randomly assigned to 1 of 2 treatment sequences. Each treatment sequence consisted of two treatment periods, each consisting of a 14-day dose titration phase followed by a 7-day dose maintenance phase. RESULTS: Of 68 patients enrolled, 33 were assigned to nabiximols followed by placebo and 35 were assigned to placebo followed by nabiximols. Least squares mean changes in MAS LLMT-6 scores from baseline to day 21 were -0.23 for nabiximols and -0.26 for placebo; the least squares mean treatment difference in MAS LLMT-6 scores for nabiximols versus placebo was 0.04, which was not statistically significant (P = 0.7152). Mean changes in MAS LLMT-4 scores from baseline to day 21 also were not significantly different between the nabiximols and placebo groups. Safety results in this study were consistent with the known safety profile of nabiximols in patients with MSS. CONCLUSION: Despite the established efficacy of nabiximols in MSS observed using patient-reported measures, the primary endpoint was not met in this study. The findings from this study reflect and emphasize some of the challenges in the evaluation and treatment of MS spasticity. CLINICAL TRIAL REGISTRATION NUMBER (CLINICALTRIALS.GOV): : NCT04657666.
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Cannabidiol , Dronabinol , Combinación de Medicamentos , Esclerosis Múltiple , Espasticidad Muscular , Humanos , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/etiología , Cannabidiol/administración & dosificación , Cannabidiol/farmacología , Dronabinol/administración & dosificación , Dronabinol/farmacología , Método Doble Ciego , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/tratamiento farmacológico , Adulto , Masculino , Vaporizadores Orales , Femenino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de SaludRESUMEN
Mitral annular disjunction (MAD) is a rare and under-recognized entity in the pediatric population. We present 2 cases of MAD in previously healthy pediatric patients and highlight clinical scenarios where MAD should be suspected.
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There are no blood-based biomarkers distinguishing patients with relapsing-remitting (RRMS) from secondary progressive multiple sclerosis (SPMS) although evidence supports metabolomic changes according to MS disease severity. Here machine learning analysis of serum metabolomic data stratified patients with RRMS from SPMS with high accuracy and a putative score was developed that stratified MS patient subsets. The top differentially expressed metabolites between SPMS versus patients with RRMS included lipids and fatty acids, metabolites enriched in pathways related to cellular respiration, notably, elevated lactate and glutamine (gluconeogenesis-related) and acetoacetate and bOHbutyrate (ketone bodies), and reduced alanine and pyruvate (glycolysis-related). Serum metabolomic changes were recapitulated in the whole blood transcriptome, whereby differentially expressed genes were also enriched in cellular respiration pathways in patients with SPMS. The final gene-metabolite interaction network demonstrated a potential metabolic shift from glycolysis toward increased gluconeogenesis and ketogenesis in SPMS, indicating metabolic stress which may trigger stress response pathways and subsequent neurodegeneration.
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INTRODUCTION: This study evaluated the impact of Financial and Insurance Navigation Assistance-Training - a pilot interprofessional training program to facilitate cost of care (CoC) conversations and address health-harming social determinants of health in a pediatric hematology-oncology clinic. METHODS: A pre-post study design was used to evaluate the impact of Financial and Insurance Navigation Assistance-Training on an interprofessional health care team's (clinicians, social workers, financial navigator, and legal advocates) knowledge, attitudes, and behaviors related to CoC conversations and screening, referring, and collaborating with interprofessional team members. Data were collected via surveys administered at baseline/pretraining, immediate post-training, and 12-month post-training. RESULTS: Most health care team members (n= 21) reported improvement in their knowledge of available financial (66.7%) and legal resources (86.7%) and ability to address social needs (93.3%), financial needs (93.3%), and facilitate CoC conversations with patients and caregivers (66.7%). DISCUSSION: Improvements in attitudes and behaviors toward engaging in CoC conversations, screenings, and referrals were relatively improved as a result of the training. However, there was a lower positive rate for actual behaviors around routine screening and initiating discussions on out-of-pocket costs, suggesting a need to address barriers. Study findings highlight the importance of interprofessional education in helping health care teams address social determinants of health through effective CoC conversations.
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BACKGROUND: Pediatric, adolescent, and young adult patients with cancer and their caregivers are at high risk of financial toxicity, and few evidence-based oncology financial and legal navigation programs exist to address it. We tested the feasibility, acceptability, and preliminary effectiveness of Financial and Insurance Navigation Assistance, a novel interdisciplinary financial and legal navigation intervention for pediatric, adolescent and young adult patients and their caregivers. METHODS: We used a single-arm feasibility and acceptability trial design in a pediatric hematology and oncology clinic and collected preintervention and postintervention surveys to assess changes in financial toxicity (3 domains: psychological response/Comprehensive Score for Financial Toxicity [COST], material conditions, and coping behaviors); health-related quality of life (Patient-Reported Outcomes Measurement Information System Physical and Mental Health, Anxiety, Depression, and Parent Proxy scales); and perceived feasibility, acceptability, and appropriateness. RESULTS: In total, 45 participants received financial navigation, 6 received legal navigation, and 10 received both. Among 15 adult patients, significant improvements in FACIT-COST (P = .041) and physical health (P = .036) were noted. Among 46 caregivers, significant improvements were noted for FACIT-COST (P < .001), the total financial toxicity score (P = .001), and the parent proxy global health score (P = .0037). We were able to secure roughly $335â323 in financial benefits for 48 participants. The intervention was rated highly for feasibility, acceptability, and appropriateness. CONCLUSIONS: Integrating financial and legal navigation through Financial and Insurance Navigation Assistance was feasible and acceptable and underscores the benefit of a multidisciplinary approach to addressing financial toxicity. CLINICALTRIALS.GOV REGISTRATION: NCT05876325.