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1.
Vasc Med ; 29(3): 245-255, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38568107

RESUMEN

BACKGROUND: Arterial calcification due to deficiency of CD73 (ACDC; OMIM 211800) is a rare genetic disease resulting in calcium deposits in arteries and small joints causing claudication, resting pain, severe joint pain, and deformities. Currently, there are no standard treatments for ACDC. Our previous work identified etidronate as a potential targeted ACDC treatment, using in vitro and in vivo disease models with patient-derived cells. In this study, we test the safety and effectiveness of etidronate in attenuating the progression of lower-extremity arterial calcification and vascular blood flow based on the computed tomography (CT) calcium score and ankle-brachial index (ABI). METHODS: Seven adult patients with a confirmed genetic diagnosis of ACDC were enrolled in an open-label, nonrandomized, single-arm pilot study for etidronate treatment. They took etidronate daily for 14 days every 3 months and were examined at the NIH Clinical Center bi-annually for 3 years. They received a baseline evaluation as well as yearly follow up after treatment. Study visits included imaging studies, exercise tolerance tests with ABIs, clinical blood and urine testing, and full dental exams. RESULTS: Etidronate treatment appeared to have slowed the progression of further vascular calcification in lower extremities as measured by CT but did not have an effect in reversing vascular and/or periarticular joint calcifications in our small ACDC cohort. CONCLUSIONS: Etidronate was found to be safe and well tolerated by our patients and, despite the small sample size, appeared to show an effect in slowing the progression of calcification in our ACDC patient cohort.(ClinicalTrials.gov Identifier NCT01585402).


Asunto(s)
5'-Nucleotidasa , Ácido Etidrónico , Proteínas Ligadas a GPI , Calcificación Vascular , Humanos , Proyectos Piloto , Calcificación Vascular/tratamiento farmacológico , Calcificación Vascular/diagnóstico por imagen , Ácido Etidrónico/uso terapéutico , Ácido Etidrónico/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Resultado del Tratamiento , 5'-Nucleotidasa/genética , 5'-Nucleotidasa/deficiencia , Factores de Tiempo , Proteínas Ligadas a GPI/sangre , Índice Tobillo Braquial , Adulto , Conservadores de la Densidad Ósea/uso terapéutico , Conservadores de la Densidad Ósea/efectos adversos , Progresión de la Enfermedad , Enfermedad Arterial Periférica/tratamiento farmacológico , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/fisiopatología , Anciano , Extremidad Inferior/irrigación sanguínea , Angiografía por Tomografía Computarizada , Predisposición Genética a la Enfermedad , Flujo Sanguíneo Regional
2.
Clin Immunol ; 224: 108664, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33422677

RESUMEN

OBJECTIVE: Characterize autoantibodies and autoimmune diseases in a prospective cohort of patients with Idiopathic CD4 Lymphocytopenia (ICL) a rare immunodeficiency characterized by an absolute CD4+ T count of <300 cells/µl in the absence of HIV or HTLV infection. METHODS: Single-Center prospective study of 67 patients conducted over an 11-year period. Rheumatologic evaluation and measurement of autoantibodies were systematically conducted, and flow cytometry of immune cell subsets was performed in a subset of patients. RESULTS: 54% of referred patients had clinical evidence of autoimmunity, with 34% having at least one autoimmune disease, most commonly autoimmune thyroid disease. 19%, had autoantibodies or incomplete features of autoimmune disease. Patients with autoimmune disease had more elevated serum immunoglobulins, and more effector memory T cells than those without autoimmunity. CONCLUSIONS: Evidence of autoimmunity, including autoimmune diseases, is more prevalent in ICL than the general population, and should be considered part of this syndrome.


Asunto(s)
Autoanticuerpos/análisis , Enfermedades Autoinmunes/inmunología , Inmunofenotipificación/métodos , Linfocitopenia-T Idiopática CD4-Positiva/inmunología , Adulto , Anciano , Enfermedades Autoinmunes/complicaciones , Estudios de Cohortes , Enfermedades Transmisibles/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Linfocitopenia-T Idiopática CD4-Positiva/complicaciones , Adulto Joven
3.
Rheumatology (Oxford) ; 61(1): 163-173, 2021 12 24.
Artículo en Inglés | MEDLINE | ID: mdl-33744914

RESUMEN

OBJECTIVES: Arterial calcification due to deficiency of CD73 (ACDC) is a hereditary autosomal recessive ectopic mineralization syndrome caused by loss-of-function mutations in the ecto-5'-nucleotidase gene. Periarticular calcification has been reported but the clinical characterization of arthritis as well as the microstructure and chemical composition of periarticular calcifications and SF crystals has not been systematically investigated. METHODS: Eight ACDC patients underwent extensive rheumatological and radiological evaluation over a period of 11 years. Periarticular and synovial biopsies were obtained from four patients. Characterization of crystal composition was evaluated by compensated polarized light microscopy, Alizarin Red staining for synovial fluid along with X-ray diffraction and X-ray micro tomosynthesis scanner for periarticular calcification. RESULTS: Arthritis in ACDC patients has a clinical presentation of mixed erosive-degenerative joint changes with a median onset of articular symptoms at 17 years of age and progresses over time to the development of fixed deformities and functional limitations of small peripheral joints with, eventually, larger joint and distinct axial involvement later in life. We have identified calcium pyrophosphate and calcium hydroxyapatite (CHA) crystals in SF specimens and determined that CHA crystals are the principal component of periarticular calcifications. CONCLUSION: This is the largest study in ACDC patients to describe erosive peripheral arthropathy and axial enthesopathic calcifications over a period of 11 years and the first to identify the composition of periarticular calcifications and SF crystals. ACDC should be considered among the genetic causes of early-onset OA, as musculoskeletal disease signs may often precede vascular symptoms.


Asunto(s)
5'-Nucleotidasa/deficiencia , Calcinosis/diagnóstico por imagen , Artropatías/diagnóstico por imagen , Periartritis/diagnóstico por imagen , Enfermedades Vasculares/diagnóstico por imagen , 5'-Nucleotidasa/genética , Calcinosis/genética , Calcinosis/patología , Preescolar , Femenino , Proteínas Ligadas a GPI/genética , Humanos , Artropatías/genética , Artropatías/patología , Masculino , Persona de Mediana Edad , Periartritis/genética , Periartritis/patología , Radiografía , Enfermedades Vasculares/genética , Enfermedades Vasculares/patología
4.
J Neuroinflammation ; 17(1): 140, 2020 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-32359360

RESUMEN

BACKGROUND: Cyclooxygenase-2 (COX-2), which is rapidly upregulated by inflammation, is a key enzyme catalyzing the rate-limiting step in the synthesis of several inflammatory prostanoids. Successful positron emission tomography (PET) radioligand imaging of COX-2 in vivo could be a potentially powerful tool for assessing inflammatory response in the brain and periphery. To date, however, the development of PET radioligands for COX-2 has had limited success. METHODS: The novel PET tracer [11C]MC1 was used to examine COX-2 expression [1] in the brains of four rhesus macaques at baseline and after injection of the inflammogen lipopolysaccharide (LPS) into the right putamen, and [2] in the joints of two human participants with rheumatoid arthritis and two healthy individuals. In the primate study, two monkeys had one LPS injection, and two monkeys had a second injection 33 and 44 days, respectively, after the first LPS injection. As a comparator, COX-1 expression was measured using [11C]PS13. RESULTS: COX-2 binding, expressed as the ratio of specific to nondisplaceable uptake (BPND) of [11C]MC1, increased on day 1 post-LPS injection; no such increase in COX-1 expression, measured using [11C]PS13, was observed. The day after the second LPS injection, a brain lesion (~ 0.5 cm in diameter) with high COX-2 density and high BPND (1.8) was observed. Postmortem brain analysis at the gene transcript or protein level confirmed in vivo PET results. An incidental finding in an unrelated monkey found a line of COX-2 positivity along an incision in skull muscle, demonstrating that [11C]MC1 can localize inflammation peripheral to the brain. In patients with rheumatoid arthritis, [11C]MC1 successfully imaged upregulated COX-2 in the arthritic hand and shoulder and apparently in the brain. Uptake was blocked by celecoxib, a COX-2 preferential inhibitor. CONCLUSIONS: Taken together, these results indicate that [11C]MC1 can image and quantify COX-2 upregulation in both monkey brain after LPS-induced neuroinflammation and in human peripheral tissue with inflammation. TRIAL REGISTRATION: ClinicalTrials.gov NCT03912428. Registered April 11, 2019.


Asunto(s)
Ciclooxigenasa 2/análisis , Inflamación/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Pirimidinas , Radiofármacos , Adulto , Animales , Artritis Reumatoide/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Macaca mulatta , Persona de Mediana Edad
5.
Med Humanit ; 44(2): 137-139, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29436480

RESUMEN

Individuals with chronic autoimmune disease experience a sense of vulnerability. In part, this relates to the struggle for finding the meaning of the illness. The consequent existential distress may manifest in an unseated sense of personhood. Insight into the mechanism of this state of powerlessness and of perceived loss of agency is central to establishing a supportive clinician-patient relationship. This present exposition underscores the concept of autoimmunity as one that represents a demarcation in the psyche: one that is not just a threat to our sense of self-hood but also to our humanity. Autoimmunity exposes the challenge imposed on the relating of the self to one's own self and hence is an ontological challenge. The breach of the boundary between self and not-self that is caused by the autoimmune process culminates in feelings of alienation.


Asunto(s)
Autoinmunidad , Comprensión , Emociones , Existencialismo , Relaciones Metafisicas Mente-Cuerpo , Personeidad , Autoimagen , Enfermedad Crónica , Humanos , Relaciones Médico-Paciente , Poder Psicológico , Autoeficacia
6.
Ann Rheum Dis ; 76(5): 792-801, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28385805

RESUMEN

To develop response criteria for adult dermatomyositis (DM) and polymyositis (PM). Expert surveys, logistic regression, and conjoint analysis were used to develop 287 definitions using core set measures. Myositis experts rated greater improvement among multiple pairwise scenarios in conjoint analysis surveys, where different levels of improvement in 2 core set measures were presented. The PAPRIKA (Potentially All Pairwise Rankings of All Possible Alternatives) method determined the relative weights of core set measures and conjoint analysis definitions. The performance characteristics of the definitions were evaluated on patient profiles using expert consensus (gold standard) and were validated using data from a clinical trial. The nominal group technique was used to reach consensus. Consensus was reached for a conjoint analysis-based continuous model using absolute per cent change in core set measures (physician, patient, and extramuscular global activity, muscle strength, Health Assessment Questionnaire, and muscle enzyme levels). A total improvement score (range 0-100), determined by summing scores for each core set measure, was based on improvement in and relative weight of each core set measure. Thresholds for minimal, moderate, and major improvement were ≥20, ≥40, and ≥60 points in the total improvement score. The same criteria were chosen for juvenile DM, with different improvement thresholds. Sensitivity and specificity in DM/PM patient cohorts were 85% and 92%, 90% and 96%, and 92% and 98% for minimal, moderate, and major improvement, respectively. Definitions were validated in the clinical trial analysis for differentiating the physician rating of improvement (p<0.001). The response criteria for adult DM/PM consisted of the conjoint analysis model based on absolute per cent change in 6 core set measures, with thresholds for minimal, moderate, and major improvement.


Asunto(s)
Dermatomiositis/terapia , Evaluación de Resultado en la Atención de Salud/normas , Índice de Severidad de la Enfermedad , Adolescente , Adulto , Niño , Preescolar , Consenso , Humanos , Polimiositis/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Sensibilidad y Especificidad
7.
Ann Rheum Dis ; 76(12): 1955-1964, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-29079590

RESUMEN

OBJECTIVE: To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. METHODS: Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology and paediatric clinics worldwide. Several statistical methods were used to derive the classification criteria. RESULTS: Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cut-off of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) 'probable IIM', had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to 'definite IIM'. A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50 to <55% as 'possible IIM'. CONCLUSIONS: The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and paediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of 'definite', 'probable' and 'possible' IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.


Asunto(s)
Miositis/clasificación , Miositis/diagnóstico , Reumatología/normas , Adulto , Biopsia/normas , Niño , Consenso , Diagnóstico Diferencial , Europa (Continente) , Humanos , Músculo Esquelético/patología , Probabilidad , Valores de Referencia , Reumatología/organización & administración , Sensibilidad y Especificidad , Sociedades Médicas/organización & administración , Estados Unidos
8.
Rheumatology (Oxford) ; 56(8): 1342-1347, 2017 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-28444299

RESUMEN

Objective: The aim was to assess environmental factors associated with disease flare in juvenile and adult dermatomyositis (DM). Methods: An online survey of DM patients from the USA and Canada examined smoking, sun exposure, infections, medications, vaccines, stressful life events and physical activity during the 6 months before flares, or in the past 6 months in patients without flares. Differences were evaluated by χ 2 and Fisher's exact tests, and significant univariable results were examined in multivariable logistic regression. Residential locations before flare were correlated with the National Weather Service UV index. Results: Of 210 participants (164 juvenile and 46 adult DM), 134 (63.8%) experienced a disease flare within 2 years of the survey. Subjects more often reported disease flare after sun exposure [odds ratio (OR) = 2.0, P = 0.03], although use of photoprotective measures did not differ between those with and without flare. Urinary tract infections (OR = 16.4, P = 0.005) and gastroenteritis (OR = 3.2, P = 0.04) were more frequent in the preceding 6 months in those who flared. Subjects who flared recently used NSAIDS (OR = 3.0, P = 0.0003), blood pressure medicines (OR = 3.5, P = 0.049) or medication for depression or mood changes (OR = 12.9, P = 0.015). Moving to a new house (OR = 10.3, P = 0.053) was more common in those who flared. Only sun exposure (OR = 2.2) and NSAIDs (OR = 1.9) were significant factors in multivariable analysis. Conclusion: Certain classes of environmental agents that have been associated with the initiation of DM, including sun exposure and medications, may also play a role in disease flares.


Asunto(s)
Dermatomiositis/patología , Progresión de la Enfermedad , Acontecimientos que Cambian la Vida , Luz Solar/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antiinflamatorios no Esteroideos/efectos adversos , Antihipertensivos/efectos adversos , Canadá , Distribución de Chi-Cuadrado , Niño , Preescolar , Dermatomiositis/complicaciones , Femenino , Gastroenteritis/etiología , Humanos , Lactante , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Psicotrópicos/efectos adversos , Encuestas y Cuestionarios , Estados Unidos , Infecciones Urinarias/etiología , Adulto Joven
9.
Curr Opin Ophthalmol ; 27 Suppl 1: 3-47, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28099212

RESUMEN

Dysfunctional tear syndrome (DTS) is a common and complex condition affecting the ocular surface. The health and normal functioning of the ocular surface is dependent on a stable and sufficient tear film. Clinician awareness of conditions affecting the ocular surface has increased in recent years because of expanded research and the publication of diagnosis and treatment guidelines pertaining to disorders resulting in DTS, including the Delphi panel treatment recommendations for DTS (2006), the International Dry Eye Workshop (DEWS) (2007), the Meibomian Gland Dysfunction (MGD) Workshop (2011), and the updated Preferred Practice Pattern guidelines from the American Academy of Ophthalmology pertaining to dry eye and blepharitis (2013). Since the publication of the existing guidelines, new diagnostic techniques and treatment options that provide an opportunity for better management of patients have become available. Clinicians are now able to access a wealth of information that can help them obtain a differential diagnosis and treatment approach for patients presenting with DTS. This review provides a practical and directed approach to the diagnosis and treatment of patients with DTS, emphasizing treatment that is tailored to the specific disease subtype as well as the severity of the condition.


Asunto(s)
Síndromes de Ojo Seco , Enfermedades de los Párpados/fisiopatología , Glándulas Tarsales/fisiopatología , Lágrimas/fisiología , Blefaritis/diagnóstico , Blefaritis/fisiopatología , Blefaritis/terapia , Síndromes de Ojo Seco/diagnóstico , Síndromes de Ojo Seco/fisiopatología , Síndromes de Ojo Seco/terapia , Humanos , Queratoconjuntivitis Seca/diagnóstico , Queratoconjuntivitis Seca/fisiopatología , Queratoconjuntivitis Seca/terapia
11.
J Commun Healthc ; 17(1): 30-43, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37092755

RESUMEN

INTRODUCTION: COVID-19 has had a devastating impact on people's lives since its initial outbreak and global spread in 2020. While the U.S. government and public health officials have recommended best practices such as social distancing, wearing a mask, and avoiding large public gatherings, these orders have been met with varying levels of acceptance from the public. Given the disparate compliance, this study builds on Social Cognitive Theory (SCT) to explore individual differences and personal motivation factors in order to better understand what may influence one's likelihood to adhere to COVID-19 protective measures. METHODS: A U.S. national survey (N = 2,049) was conducted April-May 2020, roughly one month after stay-at-home orders were issued in some states. Participants were asked to report their likelihood of taking individual and community protective measures. Multivariate hierarchical linear regressions were run to analyze the extent to which participants' concerns about COVID-19's impact, individual and collective self-efficacy, coping behaviors, and personality traits influenced the dependent variables. RESULTS: Findings showed that COVID-19-related health concerns, collective efficacy, and proactive coping strategies were positively related to participants' likelihood of taking protective measures. Those with greater concerns about their general well-being and the economy, adverse coping strategies like denial and joking, as well as sensation-seeking personalities, were less likely to take protective measures. CONCLUSION: The discussion considers how individual differences fit into broader global efforts to stem COVID-19. Practical implications for public health messaging are that communication may focus on facilitating efficacy in order to boost compliance with protective measures.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Encuestas y Cuestionarios , Habilidades de Afrontamiento , Motivación
12.
Pain Med ; 14 Suppl 1: S18-22, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24373106

RESUMEN

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) have multiple established adverse effects on various organ systems. Among those associated with high mortality are gastrointestinal complications. We address the scope of the problem and the scientific basis for risk mitigation. DESIGN: This review covers the most successful of such strategies published to date. RESULTS: Mitigation strategies to enable ongoing anti-inflammatory benefit are well studied, albeit imperfect. CONCLUSIONS: Such strategies may involve the choice of NSAID or the combined use of gastroprotective measures in association with NSAIDs.


Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Gastrointestinales/prevención & control , Antiinflamatorios no Esteroideos/uso terapéutico , Antiulcerosos/uso terapéutico , Inhibidores de la Ciclooxigenasa 2/efectos adversos , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Enfermedades Gastrointestinales/epidemiología , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Humanos , Misoprostol/uso terapéutico , Inhibidores de la Bomba de Protones/uso terapéutico , Factores de Riesgo
13.
Pain Med ; 14 Suppl 1: S23-8, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24255997

RESUMEN

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are principal pharmacologic agents for symptom relief in patients with arthritis and other inflammatory conditions. Cardiovascular risk is associated with all NSAIDs, excluding aspirin. Selective inhibition of cyclo-oxygenase-2 (COX)-2 could produce a relative reduction in endothelial production of prostacyclin, while leaving the platelet production of thromboxane A2 (TXA2 ) intact. It has been speculated that this imbalance of homeostatic prostanoids might increase the risk for thrombotic events. The goal of this review is to provide physicians guidelines to mitigate cardiovascular and nephrotoxicity of NSAIDs. METHODS: We conducted a systematic literature review to determine what information is available to guide treatment decisions in this patient population. RESULTS: Selective inhibition of COX-2 could produce a relative reduction in endothelial production of prostacyclin, while leaving the platelet production of TXA2 intact. Increasing degrees of selectivity for COX-2 are associated with augmented cardiovascular risk, whereas increasing degrees of selectivity for cyclo-oxygenase-2 (COX-1) are associated with augmented gastrointestinal risk. Some NSAIDs (such as ibuprofen) can interfere with the cardioprotective effects of aspirin by competitively binding to COX-1 enzyme, resulting in increased TXA2 production Naproxen may differ from other NSAIDs in sustaining functionally important degrees of inhibition of platelet cyclooxygenase-1 activity throughout the dosing interval. CONCLUSION: It is of paramount importance to consider individual health factors when choosing therapy with NSAIDs.


Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/uso terapéutico , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Renales/inducido químicamente , Animales , Antiinflamatorios no Esteroideos/toxicidad , Enfermedades Cardiovasculares/epidemiología , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa 2/efectos adversos , Inhibidores de la Ciclooxigenasa 2/toxicidad , Humanos , Enfermedades Renales/epidemiología
14.
J Clin Invest ; 133(19)2023 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-37561579

RESUMEN

BACKGROUNDWarts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a primary immunodeficiency disorder caused by heterozygous gain-of-function CXCR4 mutations. Myelokathexis is a kind of neutropenia caused by neutrophil retention in bone marrow and in WHIM syndrome is associated with lymphopenia and monocytopenia. The CXCR4 antagonist plerixafor mobilizes leukocytes to the blood; however, its safety and efficacy in WHIM syndrome are undefined.METHODSIn this investigator-initiated, single-center, quadruple-masked phase III crossover trial, we compared the total infection severity score (TISS) as the primary endpoint in an intent-to-treat manner in 19 patients with WHIM who each received 12 months treatment with plerixafor and 12 months treatment with granulocyte CSF (G-CSF, the standard of care for severe congenital neutropenia). The treatment order was randomized for each patient.RESULTSPlerixafor was nonsuperior to G-CSF for TISS (P = 0.54). In exploratory endpoints, plerixafor was noninferior to G-CSF for maintaining neutrophil counts of more than 500 cells/µL (P = 0.023) and was superior to G-CSF for maintaining lymphocyte counts above 1,000 cells/µL (P < 0.0001). Complete regression of a subset of large wart areas occurred on plerixafor in 5 of 7 patients with major wart burdens at baseline. Transient rash occurred on plerixafor, and bone pain was more common on G-CSF. There were no significant differences in drug preference or quality of life or the incidence of drug failure or serious adverse events.CONCLUSIONPlerixafor was not superior to G-CSF in patients with WHIM for TISS, the primary endpoint. Together with wart regression and hematologic improvement, the infection severity results support continued study of plerixafor as a potential treatment for WHIM syndrome.TRIAL REGISTRATIONClinicaltrials.gov NCT02231879.FUNDINGThis study was funded by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases.


Asunto(s)
Compuestos Heterocíclicos , Síndromes de Inmunodeficiencia , Enfermedades de Inmunodeficiencia Primaria , Verrugas , Humanos , Síndromes de Inmunodeficiencia/tratamiento farmacológico , Síndromes de Inmunodeficiencia/genética , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Movilización de Célula Madre Hematopoyética/efectos adversos , Estudios Cruzados , Calidad de Vida , Compuestos Heterocíclicos/efectos adversos , Enfermedades de Inmunodeficiencia Primaria/tratamiento farmacológico , Enfermedades de Inmunodeficiencia Primaria/genética , Verrugas/tratamiento farmacológico , Verrugas/genética , Receptores CXCR4/genética
15.
Psychol Health Med ; 17(6): 629-35, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22313178

RESUMEN

Attempts to define professionalism and humanism suggest that qualities such as compliance to values, patient access, doctor-patient relationship, demeanor, professional management, personal awareness, and motivation are prominent thematic components. In this communication, we present a method for instruction in the values of humanism that may help to overcome the "curricular inertia that plagues medical education." Our approach is structured around a technique of testimonial-commentary as a novel approach to teaching humanism that does not rely upon the traditional role-modeling format. To develop effective medical school curricula for teaching humanism, we cannot rely upon the textbooks of normal and abnormal human anatomy and physiology. We must delve into the "unscientific" realms of human identity ranging from sensuality to brutality: self-preservation to sacrifice. Underneath it all, we must acknowledge that there are the ties that bind us together as people. The Seminar on Human Suffering challenges medical school educators to work with the community at large to insure that physicians will be able to serve those that seek their counsel.


Asunto(s)
Curriculum/normas , Educación Médica/métodos , Humanismo , Médicos/normas , Educación Médica/organización & administración , Humanos , Médicos/psicología
16.
Clin Ther ; 44(11): 1463-1470, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36763994

RESUMEN

PURPOSE: This study compares outcomes of therapy with OC-01 (varenicline solution) for dry eye disease in study eyes and nonstudy fellow eyes of participants in 2 pivotal clinical trials. METHODS: All 891 patients randomized to receive OC-01 (varenicline solution) 0.03 mg, OC-01 (varenicline solution) 0.06 mg, or vehicle control (VC) in each nostril twice daily for 28 days in the Phase IIb ONSET-1 (Evaluation of the Efficacy of OC-01 Nasal Spray on Signs and Symptoms of Dry Eye Disease) and Phase III ONSET-2 trials were included in this post hoc analysis. One eye was designated as the study eye. The mean change from baseline in anesthetized Schirmer test score (STS) and the percentage of eyes achieving a ≥10-mm STS improvement were compared between treatments in study and fellow eyes overall and by baseline Eye Dryness Score. FINDINGS: In the study eyes, the mean STS improvement from baseline to day 28 was 10.4 mm, 10.5 mm, and 4.9 mm in the 0.03 mg, 0.06 mg, and VC groups, respectively; comparable values in nonstudy fellow eyes were 8.7 mm, 8.8 mm, and 2.7 mm, respectively. The percentages of study eyes achieving a ≥10-mm STS improvement were 48.1%, 48.4%, and 25.9%, respectively, whereas the comparable values in nonstudy eyes were 42.9%, 43.9%, and 19.7%, respectively. No significant treatment-subgroup interactions were observed in study or fellow eye STS outcomes by baseline Eye Dryness Scores <40 and ≥40 (p > 0.05 for all). IMPLICATIONS: OC-01 (varenicline solution) nasal spray had significant tear film production improvements compared with VC in both study and fellow eyes. These findings suggest efficacy across a broad spectrum of presenting disease severity.


Asunto(s)
Síndromes de Ojo Seco , Rociadores Nasales , Humanos , Vareniclina , Síndromes de Ojo Seco/tratamiento farmacológico
17.
BJR Case Rep ; 8(3): 20210188, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36101738

RESUMEN

Appropriate counseling of patients with autoimmune connective tissue disorders (ACTDs) is often challenging for radiation oncologists, especially regarding anticipated side-effects of radiation treatment. These patients can have highly variable and unpredictable sequelae from radiation therapy, and the uncertainty builds when radiation is convoluted by the addition of concurrent chemotherapy. While many patients may experience a mild intensification of toxicity above what is expected, some patients experience much more severe toxicity. These patients become critical learning cases, enabling a better understanding of the delicate and complex ways in which radiation response is altered in the context of ACTDs while allowing other patients with similar ACTD profiles to benefit from past experience. Our report makes an important contribution to this space by describing a particularly severe case of toxicity that manifested in such a patient and the ensuing clinical decision-making. Comprehensive genotyping of classic pharmacokinetic and pharmacodynamic pathway genes (including mutations in DPD and CDA) did not reveal any signatures that might explain her enhanced toxicity and we demonstrate that severe toxicity can still manifest in the era of modern conformal radiation treatments for rectal cancer. We urge caution in the treatment of patients with rare ACTDs, but also emphasize that curative treatment should not be withheld in such patients. We conclude by advocating for the development and maintenance of a prospective multiinstitutional database of patients with ACTDs to help inform and improve future practice.

18.
Pain Manag ; 12(1): 17-23, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34164994

RESUMEN

Pain and inflammation are common experiences following ocular surgery and, if uncontrolled, can compromise patients' vision, functioning and quality of life. Corticosteroid drugs are available to manage inflammation and discomfort but have limitations in penetrating the ocular mucus barrier to reach the target ocular tissues. KPI-121 1% (INVELTYS®) is a novel formulation of loteprednol etabonate that employs innovative proprietary technology to deliver nanoparticle-sized mucus-penetrating particles to the cornea. Results from clinical trials demonstrate that KPI-121 1% is effective and well tolerated. KPI-121 1% uses mucopenetrative technology for ophthalmic use and is the only US FDA-approved twice-daily ocular corticosteroid indicated for the treatment of inflammation and pain after ocular surgery.


Asunto(s)
Antialérgicos , Calidad de Vida , Antialérgicos/uso terapéutico , Humanos , Inflamación/tratamiento farmacológico , Presión Intraocular , Dolor/tratamiento farmacológico , Complicaciones Posoperatorias
19.
Clin Ophthalmol ; 15: 2167-2178, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34079215

RESUMEN

Presbyopia is a common age-related vision disorder characterized by a progressive inability to focus on near objects. If uncorrected or under-corrected, presbyopia can significantly impact patients' quality of life. Presbyopia represents an area of considerable unmet need due to its rising prevalence worldwide as the population ages, the high proportion of under-treated individuals in some parts of the world, and the limitations of currently available corrective methods. Progressive or bifocal spectacles are associated with peripheral blur, a restricted visual field and impaired depth perception, which have been linked to an increased risk of falls in the elderly. Contact lens options can be difficult to maintain due to the development of age-related dry eye symptoms and reduced manual dexterity. Other corrective methods involve surgical interventions that modify the optics of the cornea, replace the crystalline lens, or attempt to restore active accommodation. While patients undergoing surgery report satisfactory outcomes post-operatively, many of them eventually require reading glasses. Non-invasive therapies with novel mechanisms of action are currently being investigated; these include miotic agents and UNR844, a lipoic acid choline ester. In this narrative review, available evidence on presbyopia prevalence, quality of life impact and risk factors are described, with a focus on observational studies in non-clinical settings. The diagnosis pathway and patient journey in presbyopia are outlined, and various treatment options are analyzed. The data reviewed herein reveals significant gaps in the provision of vision correction for this common condition, with a paucity of effective, non-invasive treatment options broadly accessible to presbyopic individuals.

20.
Arthritis Rheumatol ; 73(7): 1129-1134, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33455077

RESUMEN

OBJECTIVE: Latino patients are overrepresented among cases of coronavirus disease 2019 (COVID-19) and are at an increased risk of severe disease. Prevalence of COVID-19 in Latinos with rheumatic diseases is poorly reported. This study was undertaken to characterize COVID-19 clinical features and outcomes in Latino patients with rheumatic diseases. METHODS: We conducted a retrospective study of Latino patients with rheumatic diseases from an existing observational cohort in the Washington, DC area. Patients seen between April 1, 2020 and October 15, 2020 were analyzed in this study. We reviewed demographic characteristics, body mass index (BMI), comorbidities, and use of immunomodulatory therapies. An exploratory classification and regression tree (CART) analysis along with logistic regression analyses were performed to identify risk factors for COVID-19 and rheumatic disease flare. RESULTS: Of 178 Latino patients with rheumatic diseases, 32 (18%) were identified as having COVID-19, and the incidence rate of infection was found to be 3-fold higher than in the general Latino population. No patients required intensive care unit-level care. A CART analysis and multivariable logistic regression analysis identified a BMI of >30.35 as a risk factor for COVID-19 (odds ratio [OR] 3.37 [95% confidence interval (95% CI) 1.5-7.7]; P = 0.004). COVID-19 positivity was a risk factor for rheumatic disease flare (OR 4.57 [95% CI 1.2-17.4]; P = 0.02). CONCLUSION: Our findings indicate that Latino patients with rheumatic diseases have a higher rate of COVID-19 compared with the general Latino population. Obesity is a risk factor for COVID-19, and COVID-19 is a risk factor for rheumatic disease flare. Latino patients with risk factors should be closely followed up, especially post-COVID-19 in anticipation of disease flare.


Asunto(s)
COVID-19/diagnóstico , Enfermedades Reumáticas/epidemiología , Adulto , COVID-19/epidemiología , Estudios de Cohortes , Comorbilidad , Femenino , Hispánicos o Latinos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Estados Unidos
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