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2.
Nutr. hosp ; 40(4): 732-738, Juli-Agos. 2023. tab
Article in Spanish | IBECS | ID: ibc-224196

ABSTRACT

Background: the population in Latin America is aging and elders face several obstacles for good health, including an elevated frequency of vitamin D deficiency. Thus, identification of patients at high risk to develop its negative consequences should be a priority. Objective: the objective of this analysis was to determine if levels of vitamin D lower than 15 ng/ml are associated with high mortality in Mexican elderly population, from the database of the Mexican Health and Aging Study (MHAS). Methods: prospective, population study in Mexico, that included Subjects of 50 years and older who were evaluated for Serum vitamin D levels during the year 2012 (third wave of the study). Serum 25(OH)D levels were categorized into four groups, based on cutoff points used in previous studies on vitamin D and frailty: < 15, 15-< 20, 20-< 30 and ≥ 30 ng/ml. Mortality was evaluated during 2015 (fourth wave of the study). Hazard ratio was calculated (for mortality) through Cox Regression Model, adjusted for covariates. Results: we included 1626 participants, and those with lower levels of vitamin D were older, more often women, required more aid for activities of daily living, reported higher number of chronic diseases, and lower scores on cognition. The relative risk of death was 5.421 (95 % CI 2.465-11.92, p < 0.001) for the participants with vitamin D levels < 15, which after adjusting for covariates, remained statistically significant. Conclusions: levels of vitamin D lower of 15, are associated with an increase in the rate of mortality in community-dwelling senior Mexicans.(AU)


Introducción: la población en América Latina está envejeciendo y los adultos mayores enfrentan varios obstáculos para gozar de buena salud,incluida una frecuencia elevada de deficiencia de vitamina D. Por lo tanto, la identificación de pacientes con alto riesgo de desarrollar susconsecuencias negativas debe ser una prioridad.Objetivo: el objetivo de este análisis fue determinar si los niveles de vitamina D inferiores a 15 ng/ml están asociados con una alta mortalidaden la población adulta mayor mexicana, a partir de la base de datos del Estudio de Salud y Envejecimiento en México.Métodos: estudio poblacional prospectivo en México, que incluyó Sujetos de 50 años y mayores que fueron evaluados para los niveles de vitaminaD en suero durante el año 2012 (tercera ola del estudio). Los niveles séricos de 25(OH)D se clasificaron en cuatro grupos, según los puntos decorte utilizados en estudios previos sobre vitamina D y fragilidad: < 15, 15-< 20, 20-< 30 y ≥ 30 ng/ml. La mortalidad se evaluó durante 2015(cuarta ola del estudio). Se calculó la razón de riesgo (para la mortalidad) a través del modelo de regresión de Cox, ajustado por covariables.Resultados: incluimos 1626 participantes, y aquellos con niveles más bajos de vitamina D eran mayores, más a menudo mujeres, requerían másayuda para las actividades de la vida diaria, informaron un mayor número de enfermedades crónicas y puntuaciones más bajas en cognición. Elriesgo relativo de muerte fue de 5,421 (IC 95 % 2,465-11,92, p < 0,001) para los participantes con niveles de vitamina D < 15, que despuésde ajustar por covariables, se mantuvo estadísticamente significativo.Conclusiones: niveles de vitamina D inferiores a 15, se asocian con un aumento en la tasa de mortalidad en adultos mayores mexicanosresidentes en la comunidad.(AU)


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Aging , Vitamin D/administration & dosage , Vitamin D/toxicity , Mortality , Mexico , Prospective Studies
3.
Nutr Hosp ; 40(4): 732-738, 2023 Aug 28.
Article in English | MEDLINE | ID: mdl-37409711

ABSTRACT

Introduction: Background: the population in Latin America is aging and elders face several obstacles for good health, including an elevated frequency of vitamin D deficiency. Thus, identification of patients at high risk to develop its negative consequences should be a priority. Objective: the objective of this analysis was to determine if levels of vitamin D lower than 15 ng/ml are associated with high mortality in Mexican elderly population, from the database of the Mexican Health and Aging Study (MHAS). Methods: prospective, population study in Mexico, that included Subjects of 50 years and older who were evaluated for Serum vitamin D levels during the year 2012 (third wave of the study). Serum 25(OH)D levels were categorized into four groups, based on cutoff points used in previous studies on vitamin D and frailty: < 15, 15-< 20, 20-< 30 and ≥ 30 ng/ml. Mortality was evaluated during 2015 (fourth wave of the study). Hazard ratio was calculated (for mortality) through Cox Regression Model, adjusted for covariates. Results: we included 1626 participants, and those with lower levels of vitamin D were older, more often women, required more aid for activities of daily living, reported higher number of chronic diseases, and lower scores on cognition. The relative risk of death was 5.421 (95 % CI 2.465-11.92, p < 0.001) for the participants with vitamin D levels < 15, which after adjusting for covariates, remained statistically significant. Conclusions: levels of vitamin D lower of 15, are associated with an increase in the rate of mortality in community-dwelling senior Mexicans.


Introducción: Introducción: la población en América Latina está envejeciendo y los adultos mayores enfrentan varios obstáculos para gozar de buena salud, incluida una frecuencia elevada de deficiencia de vitamina D. Por lo tanto, la identificación de pacientes con alto riesgo de desarrollar sus consecuencias negativas debe ser una prioridad. Objetivo: el objetivo de este análisis fue determinar si los niveles de vitamina D inferiores a 15 ng/ml están asociados con una alta mortalidad en la población adulta mayor mexicana, a partir de la base de datos del Estudio de Salud y Envejecimiento en México. Métodos: estudio poblacional prospectivo en México, que incluyó Sujetos de 50 años y mayores que fueron evaluados para los niveles de vitamina D en suero durante el año 2012 (tercera ola del estudio). Los niveles séricos de 25(OH)D se clasificaron en cuatro grupos, según los puntos de corte utilizados en estudios previos sobre vitamina D y fragilidad: < 15, 15-< 20, 20-< 30 y ≥ 30 ng/ml. La mortalidad se evaluó durante 2015 (cuarta ola del estudio). Se calculó la razón de riesgo (para la mortalidad) a través del modelo de regresión de Cox, ajustado por covariables. Resultados: incluimos 1626 participantes, y aquellos con niveles más bajos de vitamina D eran mayores, más a menudo mujeres, requerían más ayuda para las actividades de la vida diaria, informaron un mayor número de enfermedades crónicas y puntuaciones más bajas en cognición. El riesgo relativo de muerte fue de 5,421 (IC 95 % 2,465-11,92, p < 0,001) para los participantes con niveles de vitamina D < 15, que después de ajustar por covariables, se mantuvo estadísticamente significativo. Conclusiones: niveles de vitamina D inferiores a 15, se asocian con un aumento en la tasa de mortalidad en adultos mayores mexicanos residentes en la comunidad.


Subject(s)
Activities of Daily Living , Aging , Vitamin D Deficiency , Vitamin D , Aged , Female , Humans , Aging/blood , Mexico/epidemiology , Prospective Studies , Vitamin D/blood , Vitamin D Deficiency/blood , Vitamin D Deficiency/complications , Vitamin D Deficiency/epidemiology , Vitamin D Deficiency/mortality , Vitamins , Independent Living/statistics & numerical data , Male , Middle Aged
4.
Reumatol Clin (Engl Ed) ; 18(2): 65-68, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35153038

ABSTRACT

Frida Kahlo's medical history shows sequelae of polio, a severe traumatic event that caused multiple fractures and a penetrating pelvic injury, as well as a history of countless surgeries. In her biographical accounts and her works, chronic disabling pain always appears for long periods. Besides, a chronic foot ulcer, gangrene that required amputation of the right leg, a history of abortions, and a positive Wasserman reaction suggest that the artist could have suffered from antiphospholipid antibody syndrome (APS).


Subject(s)
Antiphospholipid Syndrome , Fractures, Multiple , Paintings , Antiphospholipid Syndrome/complications , Female , Humans , Leg
5.
Reumatol. clín. (Barc.) ; 18(2): 65-68, Feb 2022. ilus
Article in English | IBECS | ID: ibc-204787

ABSTRACT

Frida Kahlo's medical history shows sequelae of polio, a severe traumatic event that caused multiple fractures and a penetrating pelvic injury, as well as a history of countless surgeries. In her biographical accounts and her works, chronic disabling pain always appears for long periods. Besides, a chronic foot ulcer, gangrene that required amputation of the right leg, a history of abortions, and a positive Wasserman reaction suggest that the artist could have suffered from antiphospholipid antibody syndrome (APS).(AU)


La historia clínica de Frida Kahlo muestra secuelas de polio, un evento traumático grave que causó múltiples fracturas y una lesión penetrante de pelvis, así como historia de incontables cirugías. En sus recuentos biográficos y en sus obras, siempre aparece dolor crónico incapacitante por largos periodos. Además, una úlcera crónica del pie, gangrena que requirió la amputación de la pierna derecha, la historia de abortos y una reacción de Wasserman positiva sugieren que la artista podría haber padecido síndrome antifosfolipídico (SAF).(AU)


Subject(s)
Humans , Female , Medical Records , Antiphospholipid Syndrome , Poliomyelitis , Neurosyphilis , Pelvis/injuries , Chronic Pain , Syphilis Serodiagnosis , Rheumatology
6.
Arch Osteoporos ; 16(1): 18, 2021 01 25.
Article in English | MEDLINE | ID: mdl-33495916

ABSTRACT

Infection by SARS-Cov-2 (COVID-19) has affected practically all the world. This joint position statement of Latin American Medical Societies provides an updated guide for the prevention, diagnosis, and treatment of osteoporotic patients in the face of possible clinical scenarios posed by the COVID-19 health crisis. BACKGROUND: Infection by SARS-Cov-2 (COVID-19) has affected practically all the world. Characterized by high contagiousness, significative morbidity, and mortality in a segment of those infected, it has overwhelmed health services and forced to redirect resources to the emergency while impacting the attention of acute non-COVID-19 and many chronic conditions. OBJECTIVE: The objective of this study is to provide an updated guide for the prevention, diagnosis, and treatment of osteoporotic patients in the face of possible clinical scenarios posed by the COVID-19 health crisis. METHODS: A task force, of bone specialists with a wide range of disciplines in the field of osteoporosis and fragility fracture, was convened with the representation of several professional associations, namely, the Mexican Association of Bone and Mineral Metabolism (AMMOM), the National College of Geriatric Medicine (CONAMEGER), the Latin American Federation of Endocrinology (FELAEN), the Mexican Federation of Colleges of Obstetrics and Gynecology (FEMECOG), the Mexican Federation of Colleges of Orthopedics and Traumatology (FEMECOT), and the Institute of Applied Sciences for Physical Activity and Sports of the University of Guadalajara (ICAAFYD). Clinical evidence was collated, and an evidence report was rapidly generated and disseminated. After finding the gaps in the available evidence, a consensus opinion of experts was made. The resulting draft was reviewed and modified accordingly, in 4 rounds, by the participants. RESULTS: The task force approved the initial guidance statements, with moderate and high consensus. These were combined, resulting in the final guidance statements on the (1) evaluation of fracture risk; (2) stratification of risk priorities; (3) indications of bone density scans and lab tests; (4) initiation and continuation of pharmacologic therapy; (5) interruptions of therapy; (6) treatment of patients with incident fracture; (7) physical therapy and fall prevention; and (8) nutritional interventions. CONCLUSION: These guidance statements are provided to promote optimal care to patients at risk for osteoporosis and fracture, during the current COVID-19 pandemic. However, given the low level of available evidence and the rapidly evolving literature, this guidance is presented as a "living document" and future updates are anticipated.


Subject(s)
COVID-19 , Medicine , Orthopedics , Osteoporosis , Traumatology , Aged , Humans , Osteoporosis/epidemiology , Osteoporosis/therapy , Pandemics , SARS-CoV-2
8.
Article in English, Spanish | MEDLINE | ID: mdl-32891542

ABSTRACT

Frida Kahlo's medical history shows sequelae of polio, a severe traumatic event that caused multiple fractures and a penetrating pelvic injury, as well as a history of countless surgeries. In her biographical accounts and her works, chronic disabling pain always appears for long periods. Besides, a chronic foot ulcer, gangrene that required amputation of the right leg, a history of abortions, and a positive Wasserman reaction suggest that the artist could have suffered from antiphospholipid antibody syndrome (APS).

9.
Adv Rheumatol ; 59(1): 47, 2019 11 09.
Article in English | MEDLINE | ID: mdl-31706348

ABSTRACT

BACKGROUND: To determine the burden of Rheumatoid Arthritis (RA) on patients' work productivity and health related quality of life (HRQoL), and examine the influence of several exposure variables; to analyze the progression of RA over 1 year and its impact on work productivity and HRQoL. METHODS: International multicenter prospective survey including patients in 18 centers in Argentina, Brazil, Colombia and Mexico with diagnosis of RA and aged between 21-55 years. The following standard questionnaires were completed at baseline and throughout a 1-year follow-up: WPAI:RA, WALS, WLQ-25, EQ-5D-3 L and SF-36. Clinical and demographic variables were also collected through interview. RESULTS: The study enrolled 290 patients on baseline visit. Overall mean scores at baseline visit were: WPAI:RA (presenteeism) = 29.5% (SD = 28.8%); WPAI:RA (absenteeism) = 9.0% (SD = 23.2%); WPAI:RA (absenteeism and presenteeism) = 8.6% (SD = 22.6%); WALS = 9.0 (SD = 6.1); WLQ-25 = 7.0% (SD = 5.1%); SF-36 Physical Scale = 39.1 (SD = 10.3) and Mental Scale = 45.4 (SD = 11.3); EQ-5D-3 L VAS = 69.8 (SD = 20.4) and EQ-5D-3 L index = 0.67 (SD = 0.23). Higher educational levels were associated with better results in WLQ-25, while previous orthopedic surgeries reduced absenteeism results of WPAI:RA and work limitations in WLQ-25. Higher disease duration was associated with decreased HRQoL. Intensification of disease activity was associated with decreased work productivity and HRQoL, except in WLQ-25. In the longitudinal analysis, worsening in disease activity was associated with a decrease in both work productivity and HRQoL. CONCLUSIONS: RA patients are dealing with workplace disabilities and limitations and loss in HRQoL, and multiple factors seems to be associated with this. Worsening of disease activity further decreased work productivity and HRQoL, stressing the importance of disease tight control.


Subject(s)
Arthritis, Rheumatoid/complications , Efficiency , Quality of Life , Work Performance , Absenteeism , Adult , Argentina , Arthritis, Rheumatoid/prevention & control , Arthritis, Rheumatoid/surgery , Brazil , Colombia , Disease Progression , Educational Status , Female , Humans , Male , Mexico , Middle Aged , Orthopedic Procedures , Patient Reported Outcome Measures , Presenteeism/statistics & numerical data , Prospective Studies , Sample Size , Statistics, Nonparametric , Young Adult
11.
Arthritis Rheumatol ; 71(7): 1174-1184, 2019 07.
Article in English | MEDLINE | ID: mdl-30816640

ABSTRACT

OBJECTIVE: Clinical trial results have shown that, in glucocorticoid-treated patients, treatment with denosumab 60 mg subcutaneously once every 6 months (Q6M) increased spine and hip bone mineral density (BMD) at month 12 significantly more than treatment with risedronate 5 mg orally once daily (QD). The present analysis was performed to compare efficacy and characterize safety through month 24. METHODS: This phase III study enrolled men and women ≥18 years old who had received ≥7.5 mg daily prednisone or equivalent for <3 months (glucocorticoid-initiating) or for ≥3 months (glucocorticoid-continuing) before screening. All patients <50 years old had a history of osteoporotic fracture. Glucocorticoid-continuing patients ≥50 years old had T scores of -2.0 or less (or -1.0 or less with fracture history). Patients were randomized (1:1) to receive denosumab 60 mg subcutaneously Q6M or risedronate 5 mg orally QD for 24 months, with daily calcium and vitamin D. RESULTS: Of 795 patients, 590 (74.2%) completed the study (in the glucocorticoid-initiating group, 109 of 145 patients treated with denosumab and 117 of 145 patients treated with risedronate; in the glucocorticoid-continuing group, 186 of 253 patients treated with denosumab and 178 of 252 patients treated with risedronate). Denosumab was superior to risedronate in increasing lumbar spine and total hip BMD at all time points assessed, among glucocorticoid-initiating patients (24-month lumbar spine: BMD increase of 6.2% versus 1.7%, respectively [P < 0.001]; 24-month total hip: BMD increase of 3.1% versus 0.0% [P < 0.001]) and among glucocorticoid-continuing patients (24-month lumbar spine: BMD increase of 6.4% versus 3.2% [P < 0.001]; 24-month total hip: BMD increase of 2.9% versus 0.5% [P < 0.001]). Adverse events, serious adverse events (including infections), and fractures were similar between treatment groups. CONCLUSION: Denosumab was superior to risedronate in terms of increases in spine and hip BMD through month 24, and the safety profile was similar between treatment groups. Denosumab may offer a new osteoporosis treatment option for glucocorticoid-treated patients.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Bone Density , Denosumab/therapeutic use , Glucocorticoids/adverse effects , Osteoporosis/drug therapy , Osteoporotic Fractures/prevention & control , Risedronic Acid/therapeutic use , Absorptiometry, Photon , Aged , Bone Remodeling , Collagen Type I/metabolism , Double-Blind Method , Female , Femur Neck/diagnostic imaging , Hip/diagnostic imaging , Humans , Lumbar Vertebrae/diagnostic imaging , Male , Middle Aged , Osteoporosis/chemically induced , Osteoporosis/metabolism , Peptide Fragments/metabolism , Peptides/metabolism , Procollagen/metabolism , Treatment Outcome
12.
Adv Rheumatol ; 59: 47, 2019. tab
Article in English | LILACS | ID: biblio-1088596

ABSTRACT

Abstract Background: To determine the burden of Rheumatoid Arthritis (RA) on patients' work productivity and health related quality of life (HRQoL), and examine the influence of several exposure variables; to analyze the progression of RA over 1 year and its impact on work productivity and HRQoL. Methods: International multicenter prospective survey including patients in 18 centers in Argentina, Brazil, Colombia and Mexico with diagnosis of RA and aged between 21-55 years. The following standard questionnaires were completed at baseline and throughout a 1-year follow-up: WPAI:RA, WALS, WLQ-25, EQ-5D-3 L and SF-36. Clinical and demographic variables were also collected through interview. Results: The study enrolled 290 patients on baseline visit. Overall mean scores at baseline visit were: WPAI:RA (presenteeism) = 29.5% (SD = 28.8%); WPAI:RA (absenteeism) = 9.0% (SD = 23.2%); WPAI:RA (absenteeism and presenteeism) = 8.6% (SD = 22.6%); WALS = 9.0 (SD = 6.1); WLQ-25 = 7.0% (SD = 5.1%); SF-36 Physical Scale = 39.1 (SD = 10.3) and Mental Scale = 45.4 (SD = 11.3); EQ-5D-3 L VAS = 69.8 (SD = 20.4) and EQ-5D-3 L index = 0.67 (SD = 0.23). Higher educational levels were associated with better results in WLQ-25, while previous orthopedic surgeries reduced absenteeism results of WPAI:RA and work limitations in WLQ-25. Higher disease duration was associated with decreased HRQoL. Intensification of disease activity was associated with decreased work productivity and HRQoL, except in WLQ-25. In the longitudinal analysis, worsening in disease activity was associated with a decrease in both work productivity and HRQoL. Conclusions: RA patients are dealing with workplace disabilities and limitations and loss in HRQoL, and multiple factors seems to be associated with this. Worsening of disease activity further decreased work productivity and HRQoL, stressing the importance of disease tight control.


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Arthritis, Rheumatoid/complications , Quality of Life , Efficiency , Work Performance , Argentina , Arthritis, Rheumatoid/surgery , Arthritis, Rheumatoid/prevention & control , Brazil , Prospective Studies , Colombia , Statistics, Nonparametric , Sample Size , Disease Progression , Orthopedic Procedures , Absenteeism , Educational Status , Presenteeism/statistics & numerical data , Patient Reported Outcome Measures , Mexico
13.
Rev Invest Clin ; 66(3): 225-33, 2014.
Article in English | MEDLINE | ID: mdl-25695238

ABSTRACT

OBJECTIVE: To measure the impact on the health-related quality of life (HRQoL) of a sample of Mexicans with vertebral fractures. MATERIAL AND METHODS: One hundred fifteen subjects with vertebral fractures were interviewed and compared with 135 subjects similar in age without the fracture. Subjects were men and women > 50 years of age with osteoporosis confirmed by bone mineral densitometry and with at least 1 vertebral fracture verified by vertebral morphometry and Xrays. The sample was recruited from two sources: The Clínica de Osteoporosis at the Instituto Nacional de Rehabilitación and a random sample from the Latin American Osteoporosis Study. The Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) validated in Spanish for the Mexican population was applied. Descriptive statistics were used for demographic and clinical aspects of the sample, as well as χ2 for categorical variables and Student t test for independent samples for continuous variables. A multiple linear regression (LR) was conducted to characterize predictive variables related to quality of life. RESULTS: Two hundred fifty subjects were interviewed; 64% of them were women. The average age of those interviewed was 73.4 ± 11.4 years; 46% of the sample had vertebral fractures; of them 43% of were lumbar and 57% thoracic; the most frequent site was L1-T12. Significant changes were found in the group with fractures in pain, physical function, social function, and mental function (p < 0.05); in women, pain and social function were different between groups (p < 0.05); and those over 70 years also presented differences in physical, social, and mental function (p < 0.05); differences were found associated with the place of recruitment being worse in their quality of life those coming from the Clínica de Osteoporosis. Two or more fractures, age, being female and widowed were significant predictors for greater deterioration of HRQoL with the LR. CONCLUSION: This is the first study looking at the HRQoL in osteoporosis related fractures in Mexicans were quality of life deterioration on physical, social, and emotional functioning was demonstrated in subjects with two vertebral fractures. Age is a determining factor for greater deterioration in all studied domains. Differences between the samples obtained at the Clínica de Osteoporosis at the Instituto Nacional de Rehabilitación and the random population exemplifying that asymptomatic fractures are common and not diagnosed. It is important to scrutinize vertebral fractures at the first level because their timely detection allows for their evaluation and treatment and diminishes the probability of a second fracture. Our results can be generalized to men and women over 50 who live in the central megalopolis and in other states of the Valley of México.


Subject(s)
Osteoporosis/complications , Osteoporotic Fractures/epidemiology , Quality of Life , Spinal Fractures/epidemiology , Aged , Aged, 80 and over , Bone Density , Female , Humans , Linear Models , Male , Mexico/epidemiology , Middle Aged , Risk Factors , Sex Factors , Spinal Fractures/etiology , Surveys and Questionnaires
14.
J Rheumatol ; 40(7): 1069-73, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23729804

ABSTRACT

OBJECTIVE: Data on when to stop use of biological agents in rheumatoid arthritis (RA) are scant. We assessed the length of remission and the rate of clinical relapse in patients with RA who had to discontinue treatment with tocilizumab (TCZ) because of the ending of longterm (5 yrs) open-label clinical trials. METHODS: All patients at 2 participating centers in Mexico were in remission, defined as Disease Activity Score 28 ≤ 2.6, with no swollen joints at the time of the last TCZ infusion. Patients were followed thereafter every 8 weeks for 12 months or until relapse. Relapse was defined as the presence of ≥ 1 swollen joint. Doses of methotrexate and antiinflammatory drugs were not changed during the followup period. RESULTS: Forty-five patients were analyzed, 87% were women (mean age 52 yrs, mean disease duration 14 yrs). During the 12 months of followup, 44% of patients maintained remission. Relapses occurred in 56% of patients: 14 during the first 3 months after the last TCZ administration. Retreatment using other agents achieved low disease activity or remission. CONCLUSION: Longterm clinical remission is possible in a number of patients with RA after suspension of TCZ. This effect has also been reported with other biologic agents. Additional data are required to support recommendations for discontinuing a biological agent after achieving remission.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Remission Induction , Adult , Aged , Drug Therapy, Combination , Female , Humans , Male , Methotrexate/therapeutic use , Middle Aged , Recurrence , Severity of Illness Index , Time Factors , Treatment Outcome
15.
Expert Rev Clin Immunol ; 8(7): 609-15, 2012 Sep.
Article in English | MEDLINE | ID: mdl-23078058

ABSTRACT

Fostamatinib (R788) is a prodrug rapidly converted to its active metabolite on oral administration. This (known as R406) is a potent inhibitor of spleen tyrosine kinase, required for the expression of a number of proinflammatory cytokines. Fostamatinib has shown significantly superior efficacy (when compared with placebo) in the control of patients with rheumatoid arthritis not responding to methotrexate in Phase II clinical trials. Treatment emergent adverse events with a higher frequency than in those on placebo included diarrhea, hypertension, urinary tract infections, neutropenia and elevated transaminases. The studied doses have shown a linear pharmacokinetic pattern and the administration of methotrexate does not affect it. Fostamatinib may have a role in the therapy of patients with rheumatoid arthritis with poor response to conventional therapy. If these results are confirmed once Phase III studies are completed, it may find a place in the evolving treatment algorithm for rheumatoid arthritis.


Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Oxazines/therapeutic use , Protein-Tyrosine Kinases/antagonists & inhibitors , Pyridines/therapeutic use , Administration, Oral , Aminopyridines , Antirheumatic Agents/administration & dosage , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/physiopathology , Clinical Trials as Topic , Humans , Morpholines , Oxazines/administration & dosage , Oxazines/adverse effects , Prodrugs/administration & dosage , Prodrugs/adverse effects , Prodrugs/therapeutic use , Pyridines/administration & dosage , Pyridines/adverse effects , Pyrimidines , Syk Kinase , Treatment Outcome
16.
Clin Rheumatol ; 29(10): 1085-91, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20632196

ABSTRACT

Osteoporosis is a generalized disease of bone that increases fracture risk. Multiple factors influence this risk, besides low bone mass. To decrease osteoporotic fractures, those patients who require preventive management should be readily identified. This paper aims to review current information on the use of the fracture risk assessment tool (FRAX) in Latin America. Bone mineral density measurement is currently the method of reference for evaluating the fracture risk and opting for treatment; but, it misses a notable proportion of individuals who have clinical risk factors for osteoporosis and fractures. FRAX was designed to predict the 10-year absolute risk of sustaining a major osteoporotic fracture or a hip fracture. Although data is available for several countries, from Latin America, only Argentina appears in the current version of the tool. Its present use in other Latin American countries is possible with some adaptations based in similarities of epidemiological information of each country with some of the existing databases. The cutoff value beyond which treatment should be initiated needs to be determined, based not only on clinical criteria, but also on economic considerations.


Subject(s)
Osteoporotic Fractures/epidemiology , Risk Assessment , Bone Density , Humans , Latin America/epidemiology , Risk
17.
Arthritis Rheum ; 58(11): 3309-18, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18975322

ABSTRACT

OBJECTIVE: Spleen tyrosine kinase (Syk) has been identified as an important modulator of immune signaling in B cells and cells bearing Fcgamma-activating receptors. R788, a prodrug of active metabolite R406, has been shown to be an inhibitor of Syk kinase, active in a variety of in vitro and in vivo models, suggesting potential activity in the treatment of rheumatoid arthritis (RA). METHODS: We enrolled 189 patients with active RA despite methotrexate therapy in a 3-month, multicenter, ascending-dose, double-blind, placebo-controlled trial. The primary end point was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 12. RESULTS: Twice-daily oral doses of 100 mg and 150 mg of R788 were significantly superior to placebo or twice-daily oral doses of 50 mg at week 12 (ACR20 achieved in 65% and 72% versus 38% and 32% of patients, respectively [P < 0.01]). ACR50 (achieved in 49% and 57% versus 19% and 17% of patients, respectively) and ACR70 (achieved in 33% and 40% versus 4% and 2% of patients, respectively) scores showed a similar pattern. Clinical effect was noted as early as 1 week after initiation of therapy. Reductions in serum interleukin-6 and matrix metalloproteinase 3 levels also occurred as early as week 1 in the groups receiving 100 mg and 150 mg R788. The major adverse effects were gastrointestinal side effects (predominantly diarrhea) and neutropenia (<1,500/mm3), both of which were dose related. CONCLUSION: These results indicate that an inhibitor of Syk kinase produces significant clinical benefits at 12 weeks in a population of patients with active RA receiving methotrexate therapy. Syk kinase may be an important new therapeutic target in RA and related autoimmune conditions.


Subject(s)
Arthritis, Rheumatoid/drug therapy , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Oxazines/therapeutic use , Prodrugs/therapeutic use , Protein-Tyrosine Kinases/antagonists & inhibitors , Pyridines/therapeutic use , Administration, Oral , Adult , Aged , Aminopyridines , Double-Blind Method , Humans , Interleukin-6/blood , Male , Matrix Metalloproteinase 3/blood , Methotrexate/therapeutic use , Middle Aged , Morpholines , Oxazines/administration & dosage , Oxazines/adverse effects , Prodrugs/administration & dosage , Prodrugs/adverse effects , Pyridines/administration & dosage , Pyridines/adverse effects , Pyrimidines , Syk Kinase
20.
Clin Rheumatol ; 26(2): 139-43, 2007 Feb.
Article in English | MEDLINE | ID: mdl-16670826

ABSTRACT

The frequency of osteoporosis and fragility fractures has been studied to a very limited extent in few developing countries. The aim of this paper is to review briefly the burden of osteoporosis and fragility fractures in these countries and to propose some strategies for the prevention and control of those conditions, considering barriers and facilitators for their implementation. The evolution of the demographic composition in most regions with developing countries shows a considerable increase in life expectancy and therefore, a significant growth in elderly population can be expected. Reports on the incidence of fragility fractures show figures in many of those countries that are comparable to those found in developed nations. Health resources (for acute treatment of fractures, their rehabilitation and chronic management, for diagnostic centers and drug therapy for osteoporosis) are limited in most of those regions and are allocated to other health priorities. Internationally accepted guidelines can be adapted to the realities of developing nations and may be promoted by organizations of health professionals and patients, but require endorsement and support by health authorities. The steps should include: (a) campaigns to increase awareness, both among the population at risk and relevant health workers; (b) the promotion of a preventive lifestyle in the general population; (c) the development of national or regional, evidence-based guidelines for the diagnosis and treatment of osteoporosis; (d) development and implementation of guidelines for the treatment of fragility fractures, their rehabilitation and prevention of falls; (e) collection of economic data on fractures and osteoporosis; and (f) development of country-specific fracture databases. These steps may help in reducing the increasing burden of osteoporotic fractures. Their implementation will require solid scientific basis and commitment from policy makers, health professionals, patient organizations, and ultimately the general population.


Subject(s)
Developing Countries , Fractures, Spontaneous/etiology , Fractures, Spontaneous/prevention & control , Health Policy , Osteoporosis/complications , Developing Countries/economics , Developing Countries/statistics & numerical data , Fractures, Spontaneous/economics , Health Care Costs , Health Policy/economics , Humans , Osteoporosis/economics
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