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OBJECTIVES: Trauma has been linked to incident SLE, but its relationship with SLE disease activity is unknown. This analysis examines associations between trauma exposures and patient-reported SLE disease activity and flares. METHODS: Data were from the California Lupus Epidemiology Study (CLUES). Flares were self-reported as any flare and, of those, flares accompanied by medical care (hospitalization or physician contact). The Systemic Lupus Activity Questionnaire (SLAQ) assessed disease activity. The Brief Trauma Questionnaire (BTQ) assessed all historical trauma exposures. The Adverse Childhood Experiences (ACEs) questionnaire was available for a subset. Multivariable regression analyses (n = 252) examined whether trauma exposure was associated with flares or SLAQ controlling for age, sex, poverty, race/ethnicity, comorbidities, perceived stress, disease duration and self-reported disease damage. RESULTS: Excluding exposure to serious illness, 63.4% reported ≥1 trauma exposure. Any traumatic event, excluding illness, doubled the odds of a flare [OR 2.27 (95% CI 1.24, 4.17)] and was associated with significantly higher SLAQ scores [ß 2.31 (0.86, 3.76)]. Adjusted odds of any flare and flare with medical care were significantly elevated for those with both BTQ and ACE exposures [5.91 (2.21, 15.82) and 4.69 (1.56, 14.07), respectively]. SLAQ scores were also higher for those with both exposures [ß 5.22 (3.00, 7.44)]. CONCLUSION: In this cohort, those with a history of trauma reported more flares and greater disease activity. Identifying mechanisms of associations between trauma and disease activity and flares, as well as interventions to mitigate the effects of trauma exposures is critical, given the high rates of trauma exposures.
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Lupus Eritematoso Sistémico , Humanos , Autoinforme , Índice de Severidad de la Enfermedad , Lupus Eritematoso Sistémico/epidemiología , Encuestas y Cuestionarios , HospitalizaciónRESUMEN
OBJECTIVE: Concerns about the affordability of medications are common in systemic lupus erythematosus (SLE), but the relationship between medication cost concerns and health outcomes is poorly understood. We assessed the association of self-reported medication cost concerns and patient-reported outcomes (PROs) in a multiethnic SLE cohort. METHODS: The California Lupus Epidemiology Study is a cohort of individuals with physician-confirmed SLE. Medication cost concerns were defined as having difficulties affording SLE medications, skipping doses, delaying refills, requesting lower-cost alternatives, purchasing medications outside the United States, or applying for patient assistance programs. Linear regression and mixed effects models assessed the cross-sectional and longitudinal association of medication cost concerns and PROs, respectively, adjusting for age, sex, race and ethnicity, income, principal insurance, immunomodulatory medications, and organ damage. RESULTS: Of 334 participants, medication cost concerns were reported by 91 (27%). Medication cost concerns were associated with worse Systemic Lupus Activity Questionnaire (SLAQ; beta coefficient [ß] 5.9, 95% CI 4.3-7.6; P < 0.001), 8-item Patient Health Questionnaire depression scale (PHQ-8; ß 2.7, 95% CI 1.4-4.0; P < 0.001), and Patient-Reported Outcomes Measurement Information System (PROMIS; ß for physical function -4.6, 95% CI -6.7 to -2.4; P < 0.001) scores after adjusting for covariates. Medication cost concerns were not associated with significant changes in PROs over 2-year follow-up. CONCLUSION: More than a quarter of participants reported at least 1 medication cost concern, which was associated with worse PROs. Our results reveal a potentially modifiable risk factor for poor outcomes rooted in the unaffordability of SLE care.
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Lupus Eritematoso Sistémico , Humanos , Estados Unidos , Estudios Transversales , Encuestas y Cuestionarios , Modelos Lineales , Lupus Eritematoso Sistémico/epidemiología , Medición de Resultados Informados por el PacienteRESUMEN
OBJECTIVE: Despite the recognized benefits of collecting rheumatoid arthritis (RA) outcomes measures, their use in routine care is inconsistent. Using the Consolidated Framework for Implementation Research (CFIR), we conducted semi-structured interviews with United States rheumatologists and practice personnel to assess workflows, opportunities, and challenges in collecting RA outcome measures. Using insights from interviews, we developed the RA Measures Toolkit to enhance their utilization in clinical practice. METHODS: We invited 138 RISE registry practices and 5 academic medical centers with ≥ 30 patients eligible for RA outcome measures to participate in the study. Practices were classified based on their performance in quality payment programs. Recorded interviews were transcribed verbatim and analyzed thematically using deductive and inductive techniques. The findings were used to create the RA Measures Toolkit. RESULTS: We conducted 20 interviews with 38 participants across 20 practices. Key themes within the CFIR domains highlighted the challenges and best practices in RA outcome measure collection and included: 1) Process: the variability in practices' use of RA outcome measures and the importance of streamlined workflows, 2) Intervention: challenges of integrating PROs into electronic health records (EHRs), and 3) Individual characteristics: importance of clinic culture around quality improvement. Using this data, we developed the RA Toolkit, a multimedia online resource, featuring guidelines, best practices, and educational resources to improve the efficiency of current workflows and to enhance patient care. CONCLUSION: This study identifies critical gaps in the collection of RA outcome measures in U.S. rheumatology practices and provides actionable recommendations and resources to address challenges via the RA Toolkit.
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OBJECTIVE: Trauma history is associated with SLE onset and worse patient-reported outcomes; perceived stress is associated with greater SLE disease activity. Stress perceptions vary in response to life events and may be influenced by psychosocial factors. In an SLE cohort, we examined whether stressful events associated with perceived stress, whether psychosocial factors affected perceived stress, and whether these relationships varied by prior trauma exposure. METHODS: This is a cross-sectional analysis of data from the California Lupus Epidemiology Study, an adult SLE cohort. Multivariable linear regression analyses controlling for age, gender, educational attainment, income, SLE damage, comorbid conditions, glucocorticoids ≥7.5 mg/day and depression examined associations of recent stressful events (Life Events Inventory) and positive (resilience, self-efficacy, emotional support) and negative (social isolation) psychosocial factors with perceived stress. Analyses were stratified by lifetime trauma history (Brief Trauma Questionnaire (BTQ)) and by adverse childhood experiences (ACEs) in a subset. RESULTS: Among 242 individuals with SLE, a greater number of recent stressful events was associated with greater perceived stress (beta (95% CI)=0.20 (0.07 to 0.33), p=0.003). Positive psychosocial factor score representing resilience, self-efficacy and emotional support was associated with lower perceived stress when accounting for number of stressful events (-0.67 (-0.94 to -0.40), p<0.0001); social isolation was associated with higher stress (0.20 (0.14 to 0.25), p<0.0001). In analyses stratified by BTQ trauma and ACEs, associations of psychosocial factors and perceived stress were similar between groups. However, the number of recent stressful events was significantly associated with perceived stress only for people with BTQ trauma (0.17 (0.05 to 0.29), p=0.0077) and ACEs (0.37 (0.15 to 0.58), p=0.0011). CONCLUSION: Enhancing positive and lessening negative psychosocial factors may mitigate deleterious perceived stress, which may improve outcomes in SLE, even among individuals with a history of prior trauma who may be more vulnerable to recent stressful events.
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Lupus Eritematoso Sistémico , Autoeficacia , Apoyo Social , Estrés Psicológico , Humanos , Femenino , Lupus Eritematoso Sistémico/psicología , Lupus Eritematoso Sistémico/complicaciones , Masculino , Adulto , Estrés Psicológico/psicología , Estrés Psicológico/etiología , Estrés Psicológico/complicaciones , Estudios Transversales , Persona de Mediana Edad , Resiliencia Psicológica , California/epidemiología , Acontecimientos que Cambian la Vida , Experiencias Adversas de la Infancia/psicología , Experiencias Adversas de la Infancia/estadística & datos numéricos , Encuestas y Cuestionarios , Aislamiento Social/psicología , Depresión/psicología , Depresión/epidemiología , Depresión/etiologíaRESUMEN
OBJECTIVE: Studies have suggested a potential link between traumatic experiences, psychological stress, and autoimmunity, but the impact of stress on disease activity and symptom severity in systemic lupus erythematosus (SLE) remains unclear. The present study was undertaken to examine whether increases in perceived stress independently associate with worse SLE disease outcomes over 3 years of follow-up. METHODS: Participants were drawn from the California Lupus Epidemiology Study (CLUES). Stress was measured annually using the 4-item Perceived Stress Scale (PSS). Participants with increases of ≥0.5 SD in PSS score were defined as having an increase in stress. Four outcomes were measured at the year 3 follow-up visit: physician-assessed disease activity (Systemic Lupus Erythematosus Disease Activity Index); patient-reported disease activity (Systemic Lupus Activity Questionnaire); pain (Patient-Reported Outcomes Measurement Information System [PROMIS] pain interference scale); and fatigue (PROMIS fatigue scale). Multivariable linear regression evaluated longitudinal associations of increase in stress with all 4 outcomes while controlling for potential confounders. RESULTS: The sample (n = 260) was 91% female, 36% Asian, 30% White, 22% Hispanic, and 11% African American; the mean ± SD age was 46 ± 14 years. In adjusted longitudinal analyses, increase in stress was independently associated with greater physician-assessed disease activity (P = 0.015), greater self-reported disease activity (P < 0.001), more pain (P = 0.019), and more fatigue (P < 0.001). CONCLUSION: In a racially diverse sample of individuals with SLE, those who experienced an increase in stress had significantly worse disease activity and greater symptom burden at follow-up compared to those with stress levels that remained stable or declined. Findings underscore the need for interventions to bolster stress resilience and support effective coping strategies among individuals living with lupus.
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Lupus Eritematoso Sistémico , Grupos Raciales , Humanos , Femenino , Adulto , Persona de Mediana Edad , Masculino , Dolor/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/complicaciones , Estrés Psicológico/diagnóstico , Estrés Psicológico/epidemiología , Fatiga/diagnóstico , Fatiga/epidemiología , Fatiga/complicaciones , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: Knowledge about systemic lupus erythematosus (SLE) outcomes among US Asian patients is lacking. The present study was undertaken to examine SLE disease activity, severity, and damage among Asian patients of primarily Chinese and Filipino descent in a multiethnic cohort. METHODS: California Lupus Epidemiology Study (n = 328) data were analyzed. Data were collected in English, Cantonese, Mandarin, or Spanish using validated instruments for disease activity (Systemic Lupus Erythematosus Disease Activity Index), disease severity (Lupus Severity Index [LSI]), and disease damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index). We assessed differences in SLE outcomes among racial/ethnic groups using multivariable linear regression including interaction terms for age at diagnosis and race/ethnicity. RESULTS: Asian was the largest racial/ethnic group (38% [Chinese = 22%; Filipino = 9%; Other = 7%]). Average age at diagnosis was younger among Asian patients (27.9 years), particularly Filipino patients (22.2 years), compared with White (29.4 years) and Black patients (34.0 years). After adjustment, disease activity and damage were not significantly different across groups. Disease severity among Asian patients was significantly higher than among White patients (LSI score 7.1 versus 6.5; P < 0.05) but similar among Black and Hispanic patients. Early age at diagnosis was associated with greater organ damage among Asian, Black, and Hispanic patients, but not White patients. CONCLUSION: SLE was more severe among US Asian patients compared to White patients. Filipinos were affected at strikingly young ages. Asian patients and non-White groups with younger age at diagnosis had greater organ damage than White patients. Such racial/ethnic distinctions suggest the need for heightened clinical awareness to improve health outcomes among Asian patients with SLE. Further study of SLE outcomes across a range of US Asian subgroups is important.
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Lupus Eritematoso Sistémico , Pueblo Asiatico , Estudios de Cohortes , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/epidemiología , Grupos Raciales , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: Physical activity is known to improve depressive symptoms. The present study was undertaken to examine physical inactivity as a predictor of incident depression in systemic lupus erythematosus (SLE). METHODS: Data derive from the California Lupus Epidemiology Study (CLUES), a longitudinal cohort with confirmed SLE diagnoses. Physical inactivity was assessed from a single item, "I rarely or never do any physical activities," and depressive symptoms by the 8-item Patient Health Questionnaire (PHQ-8). Analysis included those not depressed at baseline (PHQ-8 score <10) who completed an in-person baseline assessment and at least 1 follow-up visit (n = 225). Incident depression was defined as a PHQ-8 score of ≥10 at follow-up. Cox proportional hazards regression modeled incident depression over 2 years as a function of baseline physical inactivity, controlling for age, sex, race, income, comorbidities, disease activity, and disease damage. RESULTS: At baseline, the mean ± SD age of the participants was 45 ± 15 years, 88% were female, and 70% identified as non-White. Mean PHQ scores for those without depression at baseline did not differ by activity status, but those who were inactive at baseline were significantly more likely to develop depression over the next 2 years (hazard ratio [HR] 2.89 [95% confidence interval (95% CI) 1.46-5.71]). After adjusting for covariates, the association remained strong, including a >3-fold increased risk of incident depression among the sedentary group (HR 3.88 [95% CI 1.67-9.03]). CONCLUSION: In this diverse SLE cohort, a simple question about physical inactivity was highly predictive of incident depression over the subsequent 2 years. Results suggest an urgent need for approaches to reduce sedentary behavior in this high-risk population.
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Lupus Eritematoso Sistémico , Conducta Sedentaria , Adulto , Estudios de Cohortes , Depresión/diagnóstico , Depresión/epidemiología , Femenino , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/epidemiología , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Multiple studies have shown the microbiota to be abnormal in patients with spondyloarthritis (SpA). The purpose of this study was to explore the genetic contributions of these microbiota abnormalities. We analyzed the impact of HLA-B27 on the microbiota of children at risk for SpA and compared the microbiota of HLA-B27+ pediatric offspring of ankylosing spondylitis (AS) patients with that of HLA-B27+ children with SpA. Human DNA was obtained from the offspring for determination of HLA-B27 status and polygenic risk score (PRS). Fecal specimens were collected from both groups for sequencing of the V4 region of the 16S ribosomal RNA gene. Among the offspring of AS patients, there was slight clustering by HLA-B27 status. After adjusting for multiple comparisons, five operational taxonomic units (OTUs) representing three unique taxa distinguished the HLA-B27+ from negative children: Blautia and Coprococcus were lower in the HLA-B27+ offspring, while Faecalibacterium prausnitzii was higher. HLA-B27+ offspring without arthritis were compared to children with treatment-naïve HLA-B27+ SpA. After adjustments, clustering by diagnosis was present. A total of 21 OTUs were significantly associated with diagnosis state, including Bacteroides (higher in SpA patients) and F. prausnitzii (higher in controls). Thus, our data confirmed associations with B. fragilis and F. prausnitzii with juvenile SpA, and also suggest that the mechanism by which HLA-B27 is associated with SpA may not involve alterations of the microbiota.
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The authors wish to make the following correction to this paper [...].
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The transition from pediatric to adult care is the focus of growing research. It is important to identify how to direct future research efforts for maximum effect. Our goals were to perform a scoping review of the transition literature, highlight gaps in transition research, and offer stakeholder guidance on the importance and feasibility of research questions designed to fill identified gaps. The transition literature on rheumatic diseases and other common pediatric-onset chronic diseases was grouped and summarized. Based on the findings, a survey was developed and disseminated to pediatric rheumatologists and young adults with rheumatic diseases as well as their caregivers. The transitional care needs of patients, healthcare teams, and caregivers is well described in the literature. While various transition readiness scales exist, no longitudinal posttransfer study confirms their predictive validity. Multiple outcome measures are used alone or in combination to define a successful transition or intervention. Multimodal interventions are most effective at improving transition-related outcomes. How broader health policy affects transition is poorly studied. Research questions that ranked highest for importance and feasibility included those related to identifying and tracking persons with psychosocial vulnerabilities or other risk factors for poor outcomes. Interventions surrounding improving self-efficacy and health literacy were also ranked highly. In contrast to healthcare teams (n = 107), young adults/caregivers (n = 23) prioritized research surrounding improved work, school, or social function. The relevant transition literature is summarized and future research questions prioritized, including the creation of processes to identify and support young adults vulnerable to poor outcomes.
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Enfermedades Reumáticas , Reumatología , Transición a la Atención de Adultos , Adulto Joven , Niño , Humanos , Reumatología/métodos , Encuestas y Cuestionarios , CuidadoresRESUMEN
BACKGROUND: Observations among Israeli pediatric rheumatologists reveal that pediatric Juvenile Spondyloarthritis (JSpA) may present differently compared to patients from the United States (US). This study is aimed to compare the demographic and clinical variables of Israeli and US JSpA patients upon presentation. METHODS: We performed a retrospective, cross-sectional, multicenter comparison of JSpA patients among 3 large Israeli pediatric rheumatology centers and a large US pediatric rheumatology center. Patients with diagnosis of Juvenile Ankylosing Spondylitis (JAS) and/or Enthesitis-related Arthritis (ERA) were included. The demographic, clinical and radiologic features were compared. RESULTS: Overall 87 patients were included (39 Israeli, 48 US patients). Upon presentation, inflammatory back pain, sacroiliac joint tenderness and abnormal modified Schober test, were significantly more prevalent among Israeli patients (59% vs. 35.4, 48.7% vs. 16.7, and 41.2% vs. 21.5%, respectively, all p < 0.05), whereas peripheral arthritis and enthesitis were significantly more prevalent among US patients (43.6% vs. 91.7 and 7.7% vs. 39.6% in Israeli patients vs. US patients, p < 0.05). In addition, 96.7% of the Israeli patients versus 29.7% of the US patients demonstrated sacroiliitis on MRI (p < 0.001, N = 67). Less than one-third of the Israeli patients (32%) were HLA-B27 positive vs. 66.7% of US patients (p = 0.007). CONCLUSION: Israeli children with JSpA presented almost exclusively with axial disease compared to US patients who were more likely to present with peripheral symptoms. HLA B27 prevalence was significantly lower in the Israeli cohort compared to the US cohort. Further studies are needed to unravel the genetic and possibly environmental factors associated with these findings.
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Artritis Juvenil/etiología , Espondiloartritis/etiología , Adolescente , Artritis Juvenil/epidemiología , Artritis Juvenil/etnología , Artritis Juvenil/patología , Niño , Estudios Transversales , Femenino , Geografía Médica , Humanos , Israel/epidemiología , Masculino , Estudios Retrospectivos , Espondiloartritis/epidemiología , Espondiloartritis/etnología , Espondiloartritis/patología , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVE: Patient-reported outcomes (PROs) are an integral part of treat-to-target approaches in managing rheumatoid arthritis (RA). In clinical practice, however, routine collection, documentation, and discussion of PROs with patients are highly variable. The RISE LC (Rheumatology Informatics System for Effectiveness Learning Collaborative) was established to develop and share best practices in PRO collection and use across adult rheumatology practices in the United States METHODS: The goals of the RISE LC were developed through site surveys and in-person meetings. Participants completed a baseline survey on PRO collection and use in their practices. RISE LC learning sessions focused on improving communication around PROs with patients and enhancing shared decision-making in treatment plans. During the coronavirus disease 2019 (COVID-19) pandemic, the RISE LC pivoted to adapt PRO tools for telehealth. RESULTS: At baseline, all responding sites (n = 15) had established workflows for collecting PROs. Most sites used paper forms alone. PRO documentation in electronic health records was variable, with only half of the sites using structured data fields. To standardize and improve the use of PROs, participants iteratively developed a Clinical Disease Activity Index-based RA Disease Activity Communication Tool to solicit treatment goals and improve shared decision-making across sites. The COVID-19 pandemic necessitated developing a tool to gauge PROs via telehealth. CONCLUSION: The RISE LC is a continuous, structured method for implementing strategies to improve PRO collection and use in rheumatological care, initially adapting from the Learning Collaborative model and extending to include features of a learning network. Future directions include measuring the impact of standardized PRO collection and discussion on shared decision-making and RA outcomes.
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Systemic lupus erythematosus (SLE) disproportionately affects those with low socioeconomic status. Evidence from the past 2 decades has revealed clearer distinctions on the mechanisms of poverty that affect long-term outcomes in SLE. Poverty exacerbates direct, indirect, and humanistic costs and is associated with worse SLE disease damage, greater mortality, and poorer quality of life. Ongoing commitments from medicine and society are required to reduce disparities, improve access to care, and bolster resilience in persons with SLE who live in poverty.
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Accesibilidad a los Servicios de Salud , Disparidades en el Estado de Salud , Disparidades en Atención de Salud , Lupus Eritematoso Sistémico , Estado de Salud , Humanos , Lupus Eritematoso Sistémico/epidemiología , Evaluación de Resultado en la Atención de Salud , Pobreza , Calidad de Vida , Clase Social , Factores SocioeconómicosRESUMEN
OBJECTIVE: Adverse childhood experiences (ACEs) are associated with poor adult health and immune dysregulation. The impact of ACEs on patients with autoimmune disease is unknown. The present study was undertaken to compare the prevalence of ACEs in patients with systemic lupus erythematosus (SLE) to a population-based survey estimate and to investigate relationships between ACEs and SLE outcomes. METHODS: Data derived from the California Lupus Epidemiology Study (CLUES), a sample of adult patients with SLE. Participants completed a 10-item ACE questionnaire covering 3 domains (abuse, neglect, household challenges). We estimated ACE prevalence in 269 CLUES participants compared to geographically matched respondents from the 2015 California Behavioral Risk Factor Surveillance System (BRFSS), which was standardized to CLUES participant characteristics (age, sex, race/ethnicity). We examined associations of patient-reported and physician-assessed health status measures with overall ACE levels and domains using multivariable linear regression, controlling for sociodemographics, nephritis, and juvenile-onset SLE. RESULTS: Although specific domains varied, overall ACE levels were similar for CLUES and BRFSS respondents. Among SLE patients, 63.2% had ≥1 ACE, and 19.3% had ≥4. ACEs were more prevalent in those who were older, women, Latino or African American, and without college degrees, but not in those with lupus nephritis. In adjusted models, higher ACE levels and ACE domains were associated with worse patient-reported SLE activity, depression, and health status but were not significantly associated with physician-assessed SLE activity, damage, or severity. CONCLUSION: Given the association between ACE levels and important patient-reported outcomes in SLE, our study reinforces the need for prevention of ACEs in childhood and for clinical interventions to promote resilience among adults who have experienced ACEs.
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Adultos Sobrevivientes de Eventos Adversos Infantiles , Lupus Eritematoso Sistémico/epidemiología , Adulto , Negro o Afroamericano , Factores de Edad , Estudios Transversales , Femenino , Estado de Salud , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Encuestas y CuestionariosRESUMEN
OBJECTIVE: The purpose of this study is to examine the effects of zonisamide on ethanol self-administration and subjective effects in risky drinkers using a human laboratory paradigm. METHOD: We conducted a double-blind, placebo-controlled study of the effects of zonisamide 100 mg on ethanol self-administration and urge to drink in risky drinkers (N = 10) ( [1] ). RESULT: During the second hour of a 2-hour self-administration session ethanol consumption was 50% lower in the zonisamide group as compared to the placebo group. Urge to drink was also significantly lower under the zonisamide condition. CONCLUSION: These results indicate that a single dose of zonisamide reduces urge to drink and the quantity of ethanol self-administered by risky drinkers during their second hour of access to alcohol. SCIENTIFIC SIGNIFICANCE: Zonisamide may help individuals drinking at risky levels reduce their intake of alcohol.
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Consumo de Bebidas Alcohólicas/tratamiento farmacológico , Etanol/administración & dosificación , Isoxazoles/uso terapéutico , Adulto , Anticonvulsivantes/uso terapéutico , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Autoadministración , Encuestas y Cuestionarios , Factores de Tiempo , ZonisamidaRESUMEN
Neurologic manifestations of rheumatoid arthritis (RA) range in severity from mild paresthesias in the hand from carpal tunnel syndrome to sudden death due to impingement of the medulla by an eroded, vertically subluxed dens. Most neurologic complications are a consequence of articular inflammation and damage that leads to compression of adjacent structures of the central or peripheral nervous systems. Rare but serious extra-articular manifestations include inflammation of the meninges and ischemic neuropathies due to necrotizing arteritis of the vasa vasorum. Medical therapy with synthetic disease-modifying antirheumatic drugs and biological agents has diminished the incidence of serious neurologic manifestations in RA.