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Tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17) inhibitors are among the most potent treatments for inflammatory arthropathies including rheumatoid arthritis, psoriasis, and spondyloarthropathies. The availability of these biologic agents have revolutionized the management of these conditions and improved patient outcomes. Though generally safe, these biologics may contribute to the induction or exacerbation of colitis. This paradoxical colitis has been observed in patients on TNF-α inhibitor etanercept and IL-17 inhibitors (secukinumab and ixekizumab). We report a case of a 46-year-old female with psoriasis and psoriatic arthritis who presented with gastrointestinal symptoms after treatment with etanercept and IL-17 inhibitors. She was later diagnosed with paradoxical indeterminate colitis that was masked and treated by subsequent biologics given for her RA and psoriatic arthritis. In this report, we will discuss the importance of considering paradoxical colitis in the differential diagnosis for patients even several years after TNF-α/IL-17 inhibitor initiation and explain why careful consideration must be made when initiating these colitis-inducing agents to treat patients with inflammatory disorders.
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Anticuerpos Monoclonales Humanizados , Artritis Psoriásica , Colitis , Etanercept , Interleucina-17 , Humanos , Femenino , Etanercept/uso terapéutico , Etanercept/efectos adversos , Artritis Psoriásica/tratamiento farmacológico , Persona de Mediana Edad , Interleucina-17/antagonistas & inhibidores , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/diagnóstico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
Understanding the immune responses to SARS-CoV-2 vaccination is critical to optimizing vaccination strategies for individuals with autoimmune diseases, such as systemic lupus erythematosus (SLE). Here, we comprehensively analyzed innate and adaptive immune responses in 19 patients with SLE receiving a complete 2-dose Pfizer-BioNTech mRNA vaccine (BNT162b2) regimen compared with a control cohort of 56 healthy control (HC) volunteers. Patients with SLE exhibited impaired neutralizing antibody production and antigen-specific CD4+ and CD8+ T cell responses relative to HC. Interestingly, antibody responses were only altered in patients with SLE treated with immunosuppressive therapies, whereas impairment of antigen-specific CD4+ and CD8+ T cell numbers was independent of medication. Patients with SLE also displayed reduced levels of circulating CXC motif chemokine ligands, CXCL9, CXCL10, CXCL11, and IFN-γ after secondary vaccination as well as downregulation of gene expression pathways indicative of compromised innate immune responses. Single-cell RNA-Seq analysis reveals that patients with SLE showed reduced levels of a vaccine-inducible monocyte population characterized by overexpression of IFN-response transcription factors. Thus, although 2 doses of BNT162b2 induced relatively robust immune responses in patients with SLE, our data demonstrate impairment of both innate and adaptive immune responses relative to HC, highlighting a need for population-specific vaccination studies.
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COVID-19 , Lupus Eritematoso Sistémico , Humanos , Vacuna BNT162 , Vacunas contra la COVID-19 , SARS-CoV-2 , COVID-19/prevención & control , VacunaciónRESUMEN
OBJECTIVE: This study updates previous estimates of the economic burden of diagnosed diabetes, with calculation of the health resource use and indirect costs attributable to diabetes in 2022. RESEARCH DESIGN AND METHODS: We combine the demographics of the U.S. population in 2022 with diabetes prevalence, from national survey data, epidemiological data, health care cost data, and economic data, into a Cost of Diabetes Economic Model to estimate the economic burden at the population and per capita levels. Health resource use and associated medical costs are analyzed by age, sex, race/ethnicity, comorbid condition, and health service category. Data sources include national surveys (2015-2020 or most recent available), Medicare standard analytic files (2020), and administrative claims data from 2018 to 2021 for a large commercially insured population in the U.S. RESULTS: The total estimated cost of diagnosed diabetes in the U.S. in 2022 is $412.9 billion, including $306.6 billion in direct medical costs and $106.3 billion in indirect costs attributable to diabetes. For cost categories analyzed, care for people diagnosed with diabetes accounts for 1 in 4 health care dollars in the U.S., 61% of which are attributable to diabetes. On average people with diabetes incur annual medical expenditures of $19,736, of which approximately $12,022 is attributable to diabetes. People diagnosed with diabetes, on average, have medical expenditures 2.6 times higher than what would be expected without diabetes. Glucose-lowering medications and diabetes supplies account for â¼17% of the total direct medical costs attributable to diabetes. Major contributors to indirect costs are reduced employment due to disability ($28.3 billion), presenteeism ($35.8 billion), and lost productivity due to 338,526 premature deaths ($32.4 billion). CONCLUSIONS: The inflation-adjusted direct medical costs of diabetes are estimated to rise 7% from 2017 and 35% from 2012 calculations (stated in 2022 dollars). Following decades of steadily increasing prevalence of diabetes, the overall estimated prevalence in 2022 remains relatively stable in comparison to 2017. However, the absolute number of people with diabetes has grown and contributes to increased health care expenditures, particularly per capita spending on inpatient hospital stays and prescription medications. The enormous economic toll of diabetes continues to burden society through direct medical and indirect costs.
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Diabetes Mellitus , Medicare , Humanos , Anciano , Estados Unidos/epidemiología , Diabetes Mellitus/diagnóstico , Costos de la Atención en Salud , Gastos en Salud , Servicios de Salud , Costo de EnfermedadRESUMEN
In view of the limited evidence showing anti-obesity effects of synbiotics via modulation of the gut microbiota in humans, a randomized clinical trial was performed. Assessment of the metabolic syndrome traits and profiling of the fecal gut microbiota using 16S rRNA gene sequencing in overweight and obese Hong Kong Chinese individuals before and after dietary intervention with an 8-week increased consumption of fruits and vegetables and/or synbiotic supplementation was conducted. The selected synbiotic contained two probiotics (Lactobacillus acidophilus NCFM and Bifidobacterium lactis HN019) and a prebiotic (polydextrose). Fifty-five overweight or obese individuals were randomized and divided into a synbiotic group (SG; n = 19), a dietary intervention group (DG; n = 18), and a group receiving combined interventions (DSG; n = 18). DSG showed the greatest weight loss effects and number of significant differences in clinical parameters compared to its baseline values-notably, decreases in fasting glucose, insulin, HOMA-IR, and triglycerides and an increase in HDL-cholesterol. DSG lowered Megamonas abundance, which was positively associated with BMI, body fat mass, and trunk fat mass. The results suggested that increasing dietary fiber consumption from fruits and vegetables combined with synbiotic supplementation is more effective than either approach alone in tackling obesity.
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Microbioma Gastrointestinal , Síndrome Metabólico , Probióticos , Simbióticos , Humanos , Método Doble Ciego , Pueblos del Este de Asia , Hong Kong , Síndrome Metabólico/terapia , Obesidad/terapia , Sobrepeso/terapia , ARN Ribosómico 16S , Fibras de la DietaRESUMEN
BACKGROUND: Wearable devices may be useful for identification, quantification and characterization, and management of atrial fibrillation (AF). To date, consumer wrist-worn devices for AF detection using photoplethysmography-based algorithms perform only periodic checks when the user is stationary and are US Food and Drug Administration cleared for prediagnostic uses without intended use for clinical decision-making. There is an unmet need for medical-grade diagnostic wrist-worn devices that provide long-term, continuous AF monitoring. METHODS AND RESULTS: We evaluated the performance of a wrist-worn device with lead-I ECG and continuous photoplethysmography (Verily Study Watch) and photoplethysmography-based convolutional neural network for AF detection and burden estimation in a prospective multicenter study that enrolled 117 patients with paroxysmal AF. A 14-day continuous ECG monitor (Zio XT) served as the reference device to evaluate algorithm sensitivity and specificity for detection of AF in 15-minute intervals. A total of 91 857 intervals were contributed by 111 subjects with evaluable reference and test data (18.3 h/d median watch wear time). The watch was 96.1% sensitive (95% CI, 92.7%-98.0%) and 98.1% specific (95% CI, 97.2%-99.1%) for interval-level AF detection. Photoplethysmography-derived AF burden estimation was highly correlated with the reference device burden (R2=0.986) with a mean difference of 0.8% (95% limits of agreement, -6.6% to 8.2%). CONCLUSIONS: Continuous monitoring using a photoplethysmography-based convolutional neural network incorporated in a wrist-worn device has clinical-grade performance for AF detection and burden estimation. These findings suggest that monitoring can be performed with wrist-worn wearables for diagnosis and clinical management of AF. REGISTRATION INFORMATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04546763.
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Fibrilación Atrial , Aprendizaje Profundo , Humanos , Algoritmos , Fibrilación Atrial/diagnóstico , Electrocardiografía , Estudios Prospectivos , MuñecaRESUMEN
Importance: Current data are lacking regarding the risk of biologic and targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) use on the development of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). Objective: To determine the risk of developing ILD in patients with RA undergoing treatment with different b/tsDMARDs. Design, Setting, and Participants: Retrospective cohort study using claims data from the Optum Clinformatics Data Mart between December 2003 and December 2019. Adult patients with RA, 1 year or more of continuous enrollment, treatment with a b/tsDMARD of interest, and without preexisting ILD were included. Data were analyzed from October 2021 to April 2022. Exposures: New administration of adalimumab, abatacept, rituximab, tocilizumab, or tofacitinib. Main Outcomes and Measures: Crude incidence rates (IRs) for the development of ILD were calculated. The risk of ILD across different b/tsDMARDs was compared using Cox-regression models. A sensitivity analysis using a prevalent new-user cohort design compared patients treated with tofacitinib and adalimumab. Results: A total of 28â¯559 patients with RA (mean [SD] age 55.6 [13.7] years; 22â¯158 female [78%]) were treated with adalimumab (13â¯326 patients), abatacept (5676 patients), rituximab (5444 patients), tocilizumab (2548 patients), or tofacitinib (1565 patients). Crude IRs per 1000 person-years for ILD were 3.43 (95% CI 2.85-4.09) for adalimumab, 4.46 (95% CI 3.44-5.70) for abatacept, 6.15 (95% CI 4.76-7.84) for rituximab, 5.05 (95% CI 3.47-7.12) for tocilizumab, and 1.47 (95% CI 0.54-3.27) for tofacitinib. After multiple adjustments, compared with patients treated with adalimumab, patients treated with tofacitinib had a lower risk of ILD (adjusted hazard ratio [aHR] 0.31; 95% CI, 0.12-0.78; P = .009). In a prevalent new-user cohort analysis, patients treated with tofacitinib had 68% reduced risk of ILD compared with adalimumab (aHR 0.32; 95% CI 0.13-0.82; P < .001). In an adjusted model, there was a 69% reduced risk of ILD in patients treated with tofacitinib compared with patients treated with adalimumab. Conclusions and Relevance: In this retrospective cohort of patients with RA, patients treated with tofacitinib had the lowest incidence of ILD compared with patients treated with all bDMARDs evaluated, and patients treated with tofacitinib had a reduced risk of ILD compared with patients treated with adalimumab after adjusting for important covariates. Additional prospective studies are needed to better understand the role tofacitinib may play in preventing ILD in patients with RA. These results, while significant, should be interpreted with caution given the fairly small sample size of the tofacitinib group.
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Antirreumáticos , Artritis Reumatoide , Productos Biológicos , Enfermedades Pulmonares Intersticiales , Adulto , Humanos , Femenino , Persona de Mediana Edad , Antirreumáticos/uso terapéutico , Abatacept/uso terapéutico , Rituximab/efectos adversos , Estudios Retrospectivos , Incidencia , Adalimumab/uso terapéutico , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/epidemiología , Productos Biológicos/uso terapéuticoRESUMEN
OBJECTIVE: The authors examined whether timely treatment for serious mental illness and substance use disorder reduces overall health care costs in a 3-year period. METHODS: Claims data from the IBM MarketScan Research Databases (2010-2017) were analyzed. The population studied included 2,997 Medicaid enrollees and 35,805 commercial insurance enrollees ages 18-64 years with an index event for a serious mental illness and 2,315 Medicaid enrollees and 28,419 commercial insurance enrollees with an index event for a substance use disorder. Health care costs in the 3 years after an index event were calculated for enrollees who received care that met a minimum threshold for treatment and for those who did not receive such care. The Toolkit for Weighting and Analysis of Nonequivalent Groups was used to control for statistically significant differences in pretreatment characteristics between the groups. RESULTS: All health care spending for enrollees who were engaged in behavioral health treatment for substance use disorder or a serious mental illness increased from year 0 to year 1 but decreased faster than the spending of enrollees who were not engaged in treatment, with larger trends for those engaged in substance use disorder treatment. Expenses for inpatient and emergency department care decreased over the 3 follow-up years; however, spending on outpatient services was significantly higher in all 3 follow-up years for those engaged in treatment. CONCLUSIONS: Health care delivery and payment models that improve access to behavioral health treatment may reduce emergency department, inpatient, and overall health care costs for particular subpopulations.
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Medicaid , Trastornos Relacionados con Sustancias , Adolescente , Adulto , Atención Ambulatoria , Atención a la Salud , Costos de la Atención en Salud , Humanos , Persona de Mediana Edad , Trastornos Relacionados con Sustancias/terapia , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: It is common for adults with opioid use disorder (OUD) to misuse additional substances, and these individuals may be particularly at risk for adverse events, including mortality. Less is known about how continued receipt of prescription opioids or risk of adverse events (e.g., suicidality, overdose, poisoning) differs for people with co-occurring OUD and additional substance use disorders (SUDs). METHODS: We conducted a retrospective study using IBM® MarketScan® Multi-State Medicaid Database enrollment/claims data. We used logistic regression to measure the association between sample characteristics and our dependent variables. The sample consisted of non-Medicare-eligible adults aged 18-64 years who were continuously enrolled in Medicaid in 2016-2017 with an OUD diagnosis on at least one claim in 2016. RESULTS: Adults with OUD and a co-occurring SUD were more likely than adults with OUD only to have an opioid-related poisoning event (odds ratio [OR] = 1.488, p = .0052), all-cause poisoning (OR = 1.756, p < .0001), or suicidal ideation (OR = 1.796, p < .0001) but not to receive ongoing opioid prescriptions (OR = 0.973, p = .1626). Adverse events varied by OUD-SUD combination. For example, adults with OUD and cocaine use disorder had the highest odds of all-cause (OR = 2.393, p < .0001) or opioid-related (OR = 1.890, p = .0027) poisoning among those with a drug-specific diagnosis and were most likely to be diagnosed with suicidal ideation (OR = 2.465, p < .0001). CONCLUSIONS: This study provides evidence that adults with OUD and a co-occurring additional SUD have increased risk for several adverse events. Multisubstance use should be screened for and identified to determine the most appropriate course of treatment.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Medicaid , Trastornos Relacionados con Opioides/epidemiología , Adolescente , Adulto , Anciano , Analgésicos Opioides , Bases de Datos Factuales , Sobredosis de Droga/epidemiología , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Retrospectivos , Estados Unidos , Adulto JovenRESUMEN
The synthesis of a new molecule, SFIC-Cl, is reported, which features enhanced π-electron delocalization by spiroconjugation and narrowed bandgap by chlorination. SFIC-Cl is integrated into a single-crystal transistor (OFET) and organic light-emitting diode (OLED). The material demonstrates remarkable transport abilities across various solution-processed OFETs and retains efficient radiance in a near-infrared OLED emitting light at 700 nm. Furthermore, the intermolecular multi-dimensional connection of SFIC-Cl enables the fabrication of a single-component large-area (2 × 2 cm2 ) near-infrared OLED by spin-coating. The SFIC-Cl-acceptor-based solar cell shows excellent power conversion efficiency of 10.16% resulting from the broadened and strong absorption and well-matched energy levels. The study demonstrates that chlorinated spiroconjugated fused systems offer a novel direction toward the development of high-performance organic semiconductor materials for hybrid organic electronic devices.
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Reaction pathways operative when pyridinophane N-oxides are photoirradiated have been studied using time course analyses and careful isolation of photolabile intermediates with support from DFT calculations. Based on the data and the isolation of two previously unknown heterocyclophanes, we outline a unified mechanistic scheme that explains competing processes under varying photochemical conditions.
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Compuestos Aza/química , Hidrocarburos Aromáticos con Puentes/química , Rayos Ultravioleta , Aziridinas/química , Teoría Funcional de la Densidad , Conformación Molecular , Óxidos/química , Pirroles/síntesis química , Pirroles/químicaRESUMEN
BACKGROUND: Multiple substance use is common among adults who misuse opioids. Adverse consequences of drugs are more severe among multisubstance users than among single drug users. This study sought to determine whether adults with opioid use disorder (OUD) and at least one other substance use disorder (SUD) are less likely than adults with OUD only to receive certain services. METHODS: We conducted a retrospective longitudinal study using the IBM® MarketScan® Multi-State Medicaid Database. We used logistic regression to measure associations between clinical characteristics and service utilization. The sample included non-Medicare-eligible adults aged 18-64 years with at least one claim in 2016 with a primary diagnosis of OUD who were continuously enrolled in Medicaid in 2016 and 2017. RESULTS: Of the 58,745 Medicaid enrollees with an initial OUD diagnosis in 2016, 29,267 had one or more additional SUD diagnoses. In the year following diagnosis, these adults were less likely than adults with OUD only to receive OUD medication treatment (OR = 0.88, p < .0001). This was true for all specifically diagnosed co-occurring SUDS. Adults with OUD and a co-occurring SUD, however, were more likely than those with OUD only to use any type of high-intensity services. CONCLUSIONS: Adults with OUD and at least one co-occurring SUD received more intensive services, which may reflect severity and lack of OUD medication treatment before misuse escalation. Programs should account for barriers to connecting these individuals to appropriate OUD treatment.
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Analgésicos Opioides/uso terapéutico , Medicaid/tendencias , Tratamiento de Sustitución de Opiáceos/tendencias , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/epidemiología , Adolescente , Adulto , Bases de Datos Factuales/tendencias , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Tratamiento de Sustitución de Opiáceos/métodos , Estudios Retrospectivos , Estados Unidos/epidemiología , Adulto JovenRESUMEN
The synthesis of graphene nanoribbons (GNRs) that contain site-specifically substituted backbone heteroatoms is one of the essential goals that must be achieved in order to control the electronic properties of these next generation organic materials. We have exploited our recently reported solid-state topochemical polymerization/cyclization-aromatization strategy to convert the simple 1,4-bis(3-pyridyl)butadiynes 3a,b into the fjord-edge nitrogen-doped graphene nanoribbon structures 1a,b (fjord-edge N2[8]GNRs). Structural assignments are confirmed by CP/MAS 13C NMR, Raman, and XPS spectroscopy. The fjord-edge N2[8]GNRs 1a,b are promising precursors for the novel backbone nitrogen-substituted N2[8]AGNRs 2a,b. Geometry and band calculations on N2[8]AGNR 2c indicate that this class of nanoribbons should have unusual bonding topology and metallicity.
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Grafito/química , Nanotubos de Carbono/química , Nitrógeno/química , Modelos Moleculares , Estructura MolecularRESUMEN
OBJECTIVE: This study sought to develop and employ a comprehensive and standardized ultrasound (US) protocol and scoring atlas for the evaluation of features relevant to knee osteoarthritis (KOA) in a community-based cohort in the United States, with the goals of demonstrating feasibility, reliability, and validity. METHODS: We utilized data from the fourth follow-up (2016-2018) of the Johnston County OA Project, which includes individuals with (~50%) and without radiographic KOA. All participants underwent standardized knee radiography and completed standard questionnaires including the Knee Injury and Osteoarthritis Outcome Score (KOOS). Bilateral knee US images were obtained by a trained sonographer using a standardized protocol and scored by trained rheumatologists using an atlas developed for this study. A total of 396 knees were each scored by two readers according to the atlas. Associations between US features, radiographic findings (graded by an expert radiologist), and KOOS scores were assessed. RESULTS: Overall interreader reliability for US scoring was fair to moderate. The strongest correlations between US and radiographic features were seen for osteophytes, and similarly strong correlations were seen between US osteophytes and overall radiographic Kellgren-Lawrence Grade, demonstrating criterion validity. Features of effusion/synovitis and osteophytes were most associated with KOOS pain and impaired function. CONCLUSION: US is a feasible, reliable, and valid method to assess features relevant to KOA in clinical and research settings. The protocol and atlas developed in this study can be utilized to evaluate KOA in a standardized fashion in future clinical studies, enabling greater utilization of this valuable modality in osteoarthritis.
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Expanded helicenes are large, structurally flexible π-frameworks that can be viewed as building blocks for more complex chiral nanocarbons. Here we report a gram-scale synthesis of an alkyne-functionalized expanded [11]helicene and its single-step transformation into two structurally and functionally distinct types of macrocyclic derivatives: (1) a figure-eight dimer via alkyne metathesis (also gram scale) and (2) two arylene-bridged expanded helicenes via Zr-mediated, formal [2+2+n] cycloadditions. The phenylene-bridged helicene displays a substantially higher enantiomerization barrier (22.1 kcal/mol) than its helicene precursor (<11.9 kcal/mol), which makes this a promising strategy to access configurationally stable expanded helicenes. In contrast, the topologically distinct figure-eight retains the configurational lability of the helicene precursor. Despite its lability in solution, this compound forms homochiral single crystals. Here, the configuration is stabilized by an intricate network of two distinct yet interconnected helical superstructures. The enantiomerization mechanisms for all new compounds were probed using density functional theory, providing insight into the flexibility of the figure-eight and guidance for future synthetic modifications in pursuit of non-racemic macrocycles.
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Compuestos Macrocíclicos/química , Compuestos Policíclicos/química , Compuestos Macrocíclicos/síntesis química , EstereoisomerismoRESUMEN
OBJECTIVE: This study investigated recent rural-nonrural trends in the prevalence and amount of mental and substance use disorder telemedicine received by adult Medicaid beneficiaries. METHODS: An analysis of 2012-2017 claims data from the IBM MarketScan Multi-State Medicaid Database for adult beneficiaries ages 18-64 years with mental and substance use disorder diagnoses (N= 1,603,066) identified telemedicine services by using procedure modifier codes and ICD-9 and ICD-10 diagnosis codes. Unadjusted trends in telemedicine use were examined, and multivariate regression models compared the prevalence and amount of telemedicine and in-person outpatient treatment received by rural (N=428,697) and nonrural (N= 1,174,369) beneficiaries and by diagnosis. RESULTS: Rates of telemedicine treatment for mental and substance use disorders among Medicaid beneficiaries increased during the study period but remained low. Among rural beneficiaries, there was a 5.9 percentage point increase in telemedicine for mental disorders and a 1.9 percentage point increase in telemedicine for substance use disorders. After control for other individual characteristics, rural beneficiaries were more likely than nonrural beneficiaries to receive any telemedicine for mental disorder (2.2 percentage points more likely) or substance use disorder (0.6 percentage points) treatment. Receipt of telemedicine was associated with receipt of more in-person outpatient services by rural beneficiaries (11.2 more visits for mental disorders and 8.2 more for substance use disorders). CONCLUSIONS: Although provision of telemedicine for mental and substance use disorders increased during the study period and was somewhat more common among rural Medicaid beneficiaries, it remains an underused resource for addressing care shortages in rural areas.
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Medicaid/estadística & datos numéricos , Trastornos Mentales/terapia , Población Rural/estadística & datos numéricos , Trastornos Relacionados con Sustancias/terapia , Telemedicina/estadística & datos numéricos , Población Urbana/estadística & datos numéricos , Adolescente , Adulto , Atención Ambulatoria , Femenino , Humanos , Masculino , Trastornos Mentales/epidemiología , Persona de Mediana Edad , Trastornos Relacionados con Sustancias/epidemiología , Estados Unidos/epidemiología , Adulto JovenAsunto(s)
Antimaláricos/uso terapéutico , Fármacos Dermatológicos/administración & dosificación , Dermatomiositis/tratamiento farmacológico , Dermatomiositis/patología , Administración Oral , Administración Tópica , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Centros de Atención Terciaria , Resultado del Tratamiento , Estados UnidosRESUMEN
OBJECTIVE: To develop an evidence-based guideline for the pharmacologic and nonpharmacologic treatment of psoriatic arthritis (PsA), as a collaboration between the American College of Rheumatology (ACR) and the National Psoriasis Foundation (NPF). METHODS: We identified critical outcomes in PsA and clinically relevant PICO (population/intervention/comparator/outcomes) questions. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available pharmacologic and nonpharmacologic therapies for PsA. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of the evidence. A voting panel, including rheumatologists, dermatologists, other health professionals, and patients, achieved consensus on the direction and the strength of the recommendations. RESULTS: The guideline covers the management of active PsA in patients who are treatment-naive and those who continue to have active PsA despite treatment, and addresses the use of oral small molecules, tumor necrosis factor inhibitors, interleukin-12/23 inhibitors (IL-12/23i), IL-17 inhibitors, CTLA4-Ig (abatacept), and a JAK inhibitor (tofacitinib). We also developed recommendations for psoriatic spondylitis, predominant enthesitis, and treatment in the presence of concomitant inflammatory bowel disease, diabetes, or serious infections. We formulated recommendations for a treat-to-target strategy, vaccinations, and nonpharmacologic therapies. Six percent of the recommendations were strong and 94% conditional, indicating the importance of active discussion between the health care provider and the patient to choose the optimal treatment. CONCLUSION: The 2018 ACR/NPF PsA guideline serves as a tool for health care providers and patients in the selection of appropriate therapy in common clinical scenarios. Best treatment decisions consider each individual patient situation. The guideline is not meant to be proscriptive and should not be used to limit treatment options for patients with PsA.
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Antiinflamatorios no Esteroideos/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Psoriásica/terapia , Glucocorticoides/uso terapéutico , Inmunosupresores/uso terapéutico , Modalidades de Fisioterapia , Abatacept/uso terapéutico , Adalimumab/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Artritis Psoriásica/epidemiología , Comorbilidad , Diabetes Mellitus/epidemiología , Diabetes Mellitus/terapia , Entesopatía/terapia , Etanercept/uso terapéutico , Medicina Basada en la Evidencia , Ejercicio Físico , Humanos , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/terapia , Infliximab/uso terapéutico , Interleucina-12/antagonistas & inhibidores , Interleucina-17/antagonistas & inhibidores , Interleucina-23/antagonistas & inhibidores , Terapia Ocupacional , Piperidinas/uso terapéutico , Pirimidinas/uso terapéutico , Pirroles/uso terapéutico , Reumatología , Cese del Hábito de Fumar , Sociedades Médicas , Espondilitis/terapia , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Ustekinumab/uso terapéutico , Pérdida de PesoRESUMEN
OBJECTIVE: To develop an evidence-based guideline for the pharmacologic and nonpharmacologic treatment of psoriatic arthritis (PsA), as a collaboration between the American College of Rheumatology (ACR) and the National Psoriasis Foundation (NPF). METHODS: We identified critical outcomes in PsA and clinically relevant PICO (population/intervention/comparator/outcomes) questions. A Literature Review Team performed a systematic literature review to summarize evidence supporting the benefits and harms of available pharmacologic and nonpharmacologic therapies for PsA. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of the evidence. A voting panel, including rheumatologists, dermatologists, other health professionals, and patients, achieved consensus on the direction and the strength of the recommendations. RESULTS: The guideline covers the management of active PsA in patients who are treatment-naive and those who continue to have active PsA despite treatment, and addresses the use of oral small molecules, tumor necrosis factor inhibitors, interleukin-12/23 inhibitors (IL-12/23i), IL-17 inhibitors, CTLA4-Ig (abatacept), and a JAK inhibitor (tofacitinib). We also developed recommendations for psoriatic spondylitis, predominant enthesitis, and treatment in the presence of concomitant inflammatory bowel disease, diabetes, or serious infections. We formulated recommendations for a treat-to-target strategy, vaccinations, and nonpharmacologic therapies. Six percent of the recommendations were strong and 94% conditional, indicating the importance of active discussion between the health care provider and the patient to choose the optimal treatment. CONCLUSION: The 2018 ACR/NPF PsA guideline serves as a tool for health care providers and patients in the selection of appropriate therapy in common clinical scenarios. Best treatment decisions consider each individual patient situation. The guideline is not meant to be proscriptive and should not be used to limit treatment options for patients with PsA.
Asunto(s)
Artritis Psoriásica/terapia , Toma de Decisiones Clínicas , Guías de Práctica Clínica como Asunto/normas , Reumatología/normas , Antirreumáticos/administración & dosificación , Artritis Psoriásica/diagnóstico , Artritis Psoriásica/epidemiología , Productos Biológicos/administración & dosificación , Toma de Decisiones Clínicas/métodos , Quimioterapia Combinada , Humanos , Inmunosupresores/administración & dosificación , Reumatología/métodos , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
We report a computational study of mesoscale morphology and charge-transport properties of radially π-conjugated cycloparaphenylenes ([ n]CPPs) of various ring sizes ( n = 5-12, where n is the number of repeating phenyl units). These molecules are considered structural constituents of fullerenes and carbon nanotubes. [ n]CPP molecules are nested in a unique fashion in the solid state. Molecular dynamics simulations show that while intramolecular structural stability (order) increases with system size, intermolecular structural stability decreases. Density functional calculations reveal that reorganization energy, an important parameter in charge transfer, decreases as n is increased. Intermolecular charge-transfer electronic couplings in the solid state are relatively weak (due to curved π-conjugation and loose intermolecular contacts) and are on the same order of magnitude (â¼10 meV) for each system. Intrinsic charge-carrier mobilities were simulated from kinetic Monte Carlo simulations; hole mobilities increased with system size and scaled as â¼ n4. We predict that disordered [ n]CPPs exhibit hole mobilities as high as 2 cm2/(V·s). Our computations show a strong correlation between reorganization energy and hole mobility (µ â¼ λ-4). Quantum mechanical calculations were performed on cofacially stacked molecular pairs for varying phenyl units and reveal that orbital delocalization is responsible for both decreasing reorganization energies and electronic couplings as n is increased.
RESUMEN
We report a computational study on the effect of side-chain substitution, heteroaromatic substitution and unique crystal packing on the charge transport and mobility of three double helicene molecules. These double helicene (DH) molecules, having curved π-conjugation, are structural hybrids of non-planar [6]helicene and planar tribenzo[b,n,pqr]perylene (TBP). We find that side-chain substitution has only a effect on intrinsic electronic properties in DHs but dramatically impacts the packing arrangement, morphologies and transport network, exhibited in calculated charge transport parameters. Interestingly, the dimensionality of the transport evolves from one dimensional to three dimensional with side-chain substitution (DH2) and heteroaromatic substitution (DH3). Using two different well-known transport models, we have established a direct link between the morphology, transport connectivity, and hole mobilities. While both unsubstituted and substituted DHs exhibit high hole mobilities in the ordered phase, the results show that with inclusion of positional disorder, the mobilities of disordered DH1 and DH3 are lower while the mobility of DH2 remain nearly unchanged. We relate this effect to the dimensionality of their unique transport networks. These DH molecules are promising organic semiconductors with high mobilities in ordered and disordered phases, with predicted values that lie in the range of â¼1 to 10 cm2 V-1 s-1.