RESUMEN
This secondary analysis of a randomized clinical trial analyzes the association of vitamin C supplementation in women who smoked during pregnancy with airway function trajectory in their offspring at 4 to 6 years of age.
Asunto(s)
Ácido Ascórbico , Suplementos Dietéticos , Humanos , Embarazo , Femenino , Ácido Ascórbico/administración & dosificación , Efectos Tardíos de la Exposición Prenatal , Masculino , FumarRESUMEN
BACKGROUND: We previously reported in the "Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function" randomized clinical trial (RCT) that vitamin C (500 mg/day) supplementation to pregnant smokers is associated with improved respiratory outcomes that persist through 5 years of age. The objective of this study was to assess whether buccal cell DNA methylation (DNAm), as a surrogate for airway epithelium, is associated with vitamin C supplementation, improved lung function, and decreased occurrence of wheeze. METHODS: We conducted epigenome-wide association studies (EWAS) using Infinium MethylationEPIC arrays and buccal DNAm from 158 subjects (80 placebo; 78 vitamin C) with pulmonary function testing (PFT) performed at the 5-year visit. EWAS were performed on (1) vitamin C treatment, (2) forced expiratory flow between 25 and 75% of expired volume (FEF25-75), and (3) offspring wheeze. Models were adjusted for sex, race, study site, gestational age at randomization (≤ OR > 18 weeks), proportion of epithelial cells, and latent covariates in addition to child length at PFT in EWAS for FEF25-75. We considered FDR p < 0.05 as genome-wide significant and nominal p < 0.001 as candidates for downstream analyses. Buccal DNAm measured in a subset of subjects at birth and near 1 year of age was used to determine whether DNAm signatures originated in utero, or emerged with age. RESULTS: Vitamin C treatment was associated with 457 FDR significant (q < 0.05) differentially methylated CpGs (DMCs; 236 hypermethylated; 221 hypomethylated) and 53 differentially methylated regions (DMRs; 26 hyper; 27 hypo) at 5 years of age. FEF25-75 was associated with one FDR significant DMC (cg05814800), 1,468 candidate DMCs (p < 0.001), and 44 DMRs. Current wheeze was associated with 0 FDR-DMCs, 782 candidate DMCs, and 19 DMRs (p < 0.001). In 365/457 vitamin C FDR significant DMCs at 5 years of age, there was no significant interaction between time and treatment. CONCLUSIONS: Vitamin C supplementation to pregnant smokers is associated with buccal DNA methylation in offspring at 5 years of age, and most methylation signatures appear to be persistent from the prenatal period. Buccal methylation at 5 years was also associated with current lung function and occurrence of wheeze, and these functionally associated loci are enriched for vitamin C associated loci. Clinical trial registration ClinicalTrials.gov, NCT01723696 and NCT03203603.
Asunto(s)
Ácido Ascórbico , Metilación de ADN , Fumadores , Vitaminas , Femenino , Humanos , Lactante , Embarazo , Ácido Ascórbico/uso terapéutico , Suplementos Dietéticos , Pulmón , Ruidos Respiratorios/genética , Vitaminas/uso terapéutico , Preescolar , Fenómenos Fisiologicos Nutricionales MaternosRESUMEN
Importance: Vitamin C supplementation (500 mg/d) for pregnant smokers has been reported to increase offspring airway function as measured by forced expiratory flow (FEF) through age 12 months; however, its effects on airway function at age 5 years remain to be assessed. Objective: To assess whether vitamin C supplementation in pregnant smokers is associated with increased and/or improved airway function in their offspring at age 5 years and whether vitamin C decreases the occurrence of wheeze. Design, Setting, and Participants: This study followed up the Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP) double-blind, placebo-controlled randomized clinical trial conducted at 3 centers in the US (in Oregon, Washington, and Indiana) between 2012 and 2016. Investigators and participants remain unaware of the treatment assignments. Forced expiratory flow measurements at age 5 years were completed from 2018 to 2021. Interventions: Pregnant smokers were randomized to vitamin C (500 mg/d) or placebo treatment. Main Outcomes and Measures: The primary outcome was the prespecified measurement of FEF between 25% and 75% expired volume (FEF25-75) by spirometry at age 5 years. Secondary outcomes included FEF measurements at 50% and 75% of expiration (FEF50 and FEF75), forced expiratory volume in 1 second (FEV1), and occurrence of wheeze. Results: Of the 251 pregnant smokers included in this study, 125 (49.8%) were randomized to vitamin C and 126 (50.2%) were randomized to placebo. Of 213 children from the VCSIP trial who were reconsented into this follow-up study, 192 (90.1%) had successful FEF measurements at age 5 years; 212 (99.5%) were included in the analysis of wheeze. Analysis of covariance demonstrated that offspring of pregnant smokers allocated to vitamin C compared with placebo had 17.2% significantly higher mean (SE) measurements of FEF25-75 at age 5 years (1.45 [0.04] vs 1.24 [0.04] L/s; adjusted mean difference, 0.21 [95% CI, 0.13-0.30]; P < .001). Mean (SE) measurements were also significantly increased by 14.1% for FEF50 (1.59 [0.04] vs 1.39 [0.04] L/s; adjusted mean difference, 0.20 [95% CI, 0.11-0.30]; P < .001), 25.9% for FEF75 (0.79 [0.02] vs 0.63 [0.02] L/s; 0.16 [95% CI, 0.11-0.22]; P < .001), and 4.4% for FEV1 (1.13 [0.02] vs 1.09 [0.02] L; 0.05 [95% CI, 0.01-0.09]; P = .02). In addition, offspring of pregnant smokers randomized to vitamin C had significantly decreased wheeze (28.3% vs 47.2%; estimated odds ratio, 0.41 [95% CI, 0.23-0.74]; P = .003). Conclusions and Relevance: In this follow-up study of offspring of pregnant smokers randomized to vitamin C vs placebo, vitamin C supplementation during pregnancy resulted in significantly increased airway function of offspring at age 5 years and significantly decreased the occurrence of wheeze. These findings suggest that vitamin C supplementation for pregnant smokers may decrease the effects of smoking in pregnancy on childhood airway function and respiratory health. Trial Registration: ClinicalTrials.gov Identifier: NCT03203603.
Asunto(s)
Fumadores , Fumar , Lactante , Embarazo , Niño , Femenino , Humanos , Preescolar , Estudios de Seguimiento , Fumar/efectos adversos , Suplementos Dietéticos , Vitaminas/uso terapéutico , Ácido Ascórbico/uso terapéutico , Ruidos Respiratorios , Método Doble CiegoRESUMEN
Lipoic acid (alpha lipoic acid, thioctic acid) is a popular over-the-counter antioxidant and insulin-mimetic supplement under investigation in a variety of conditions including multiple sclerosis, diabetes, and schizophrenia. Unfortunately, high-grade proteinuria was an unexpected adverse event specific to the treatment arm of our clinical trial investigating lipoic acid supplementation in patients with multiple sclerosis. This observation led to detection of similar patients in our nephrology practice. Here, we describe four biopsy-proven cases of neural epidermal growth factor-like 1 (NELL1)-associated membranous nephropathy following lipoic acid supplementation and a fifth suspected case. Discontinuation of lipoic acid and supportive therapy resulted in remission.
Asunto(s)
Glomerulonefritis Membranosa , Ácido Tióctico , Proteínas de Unión al Calcio , Suplementos Dietéticos , Familia de Proteínas EGF , Glomerulonefritis Membranosa/diagnóstico , Glomerulonefritis Membranosa/tratamiento farmacológico , Humanos , Proteinuria/inducido químicamente , Proteinuria/tratamiento farmacológico , Ácido Tióctico/efectos adversosRESUMEN
BACKGROUND: Maternal smoking during pregnancy (MSDP) affects development of multiple organ systems including the placenta, lung, brain, and vasculature. In particular, children exposed to MSDP show lifelong deficits in pulmonary function and increased risk of asthma and wheeze. Our laboratory has previously shown that vitamin C supplementation during pregnancy prevents some of the adverse effects of MSDP on offspring respiratory outcomes. Epigenetic modifications, including DNA methylation (DNAm), are a likely link between in utero exposures and adverse health outcomes, and MSDP has previously been associated with DNAm changes in blood, placenta, and buccal epithelium. Analysis of placental DNAm may reveal critical targets of MSDP and vitamin C relevant to respiratory health outcomes. RESULTS: DNAm was measured in placentas obtained from 72 smokers enrolled in the VCSIP RCT: NCT03203603 (37 supplemented with vitamin C, 35 with placebo) and 24 never-smokers for reference. Methylation at one CpG, cg20790161, reached Bonferroni significance and was hypomethylated in vitamin C supplemented smokers versus placebo. Analysis of spatially related CpGs identified 93 candidate differentially methylated regions (DMRs) between treatment groups, including loci known to be associated with lung function, oxidative stress, fetal development and growth, and angiogenesis. Overlap of nominally significant differentially methylated CpGs (DMCs) in never-smokers versus placebo with nominally significant DMCs in vitamin C versus placebo identified 9059 candidate "restored CpGs" for association with placental transcript expression and respiratory outcomes. Methylation at 274 restored candidate CpG sites was associated with expression of 259 genes (FDR < 0.05). We further identified candidate CpGs associated with infant lung function (34 CpGs) and composite wheeze (1 CpG) at 12 months of age (FDR < 0.05). Increased methylation in the DIP2C, APOH/PRKCA, and additional candidate gene regions was associated with improved lung function and decreased wheeze in offspring of vitamin C-treated smokers. CONCLUSIONS: Vitamin C supplementation to pregnant smokers ameliorates changes associated with maternal smoking in placental DNA methylation and gene expression in pathways potentially linked to improved placental function and offspring respiratory health. Further work is necessary to validate candidate loci and elucidate the causal pathway between placental methylation changes and outcomes of offspring exposed to MSDP. Clinical trial registration ClinicalTrials.gov, NCT01723696. Registered November 6, 2012. https://clinicaltrials.gov/ct2/show/record/NCT01723696 .
Asunto(s)
Ácido Ascórbico/farmacología , Metilación de ADN/efectos de los fármacos , Placenta/fisiopatología , Fumar/efectos adversos , Adulto , Ácido Ascórbico/administración & dosificación , Suplementos Dietéticos/normas , Suplementos Dietéticos/estadística & datos numéricos , Femenino , Humanos , Placenta/patología , Embarazo , Efectos Tardíos de la Exposición Prenatal/genética , Fumar/fisiopatologíaRESUMEN
BACKGROUND: Vitamin C (500â mg·day-1) supplementation for pregnant smokers has been reported to increase newborn pulmonary function and infant forced expiratory flows (FEFs) at 3â months of age. Its effect on airway function through 12â months of age has not been reported. OBJECTIVE: To assess whether vitamin C supplementation to pregnant smokers is associated with a sustained increased airway function in their infants through 12â months of age. METHODS: This is a prespecified secondary outcome of a randomised, double-blind, placebo-controlled trial that randomised 251 pregnant smokers between 13 and 23â weeks of gestation: 125 to 500â mg·day-1 vitamin C and 126 to placebo. Smoking cessation counselling was provided. FEFs performed at 3 and 12â months of age were analysed by repeated measures analysis of covariance. RESULTS: FEFs were performed in 222 infants at 3â months and 202 infants at 12â months of age. The infants allocated to vitamin C had significantly increased FEFs over the first year of life compared to those allocated to placebo. The overall increased flows were: 40.2â mL·sec-1 for FEF75 (adjusted 95% CI for difference 6.6 to 73.8; p=0.025); 58.3â mL·sec-1 for FEF50 (95% CI 10.9 to 105.8; p=0.0081); and 55.1â mL·sec-1 for FEF25-75 (95% CI, 9.7 to 100.5; p=0.013). CONCLUSIONS: In offspring of pregnant smokers randomised to vitamin C versus placebo, vitamin C during pregnancy was associated with a small but significantly increased airway function at 3 and 12â months of age, suggesting a potential shift to a higher airway function trajectory curve. Continued follow-up is underway.
Asunto(s)
Ácido Ascórbico , Fumadores , Suplementos Dietéticos , Femenino , Humanos , Lactante , Embarazo , VitaminasRESUMEN
Rationale: We reported a randomized trial demonstrating daily supplemental vitamin C to pregnant smokers significantly improved newborn pulmonary function tests. The current study tests these results in a new cohort using infant pulmonary function tests. Objectives: To determine if infants of pregnant smokers randomized to daily supplemental vitamin C would have improved forced expiratory flows (FEFs) at 3 months of age compared with those randomized to placebo, and to investigate the association of the α5 nicotinic acetylcholine receptor. Methods: A randomized, double-blind, placebo-controlled trial was conducted at three centers. Two hundred fifty-one pregnant smokers were randomized at 13-23 weeks of gestation: 125 randomized to vitamin C (500 mg/d) and 126 to placebo. Measurements and Main Results: The primary outcome was FEF75 at 3 months of age performed with the raised volume rapid thoracic compression technique (Jaeger/Viasys). FEF50 and FEF25-75 obtained from the same expiratory curves were prespecified secondary outcomes. The infants of pregnant smokers randomized to vitamin C (n = 113) had the following FEFs at 3 months of age compared with those randomized to placebo (n = 109) as measured by FEF75 (200.7 vs. 188.7 ml/s; adjusted 95% confidence interval [CI] for difference, -3.33 to 35.64; P = 0.10), FEF50 (436.7 vs. 408.5 ml/s; adjusted 95% CI for difference, 6.10-61.30; P = 0.02), and FEF25-75 (387.4 vs. 365.8 ml/s; adjusted 95% CI for difference, 0.92-55.34; P = 0.04). Infant FEFs seemed to be negatively associated with the maternal risk alleles for the α5 nicotinic acetylcholine receptor (rs16969968). Conclusions: Although the primary outcome of FEF75 was not improved after vitamin C supplementation to pregnant smokers, the predetermined secondary outcomes FEF50 and FEF25-75 were significantly improved. These results extend our previous findings and demonstrate improved airway function (FEF50 and FEF25-75) at 3 months of age in infants after vitamin C supplementation to pregnant smokers. Clinical trial registered with www.clinicaltrials.gov (NCT01723696).
Asunto(s)
Ácido Ascórbico/uso terapéutico , Efectos Tardíos de la Exposición Prenatal/prevención & control , Fumar/efectos adversos , Administración Oral , Adulto , Ácido Ascórbico/administración & dosificación , Suplementos Dietéticos , Método Doble Ciego , Femenino , Flujo Espiratorio Forzado , Humanos , Lactante , Embarazo , Complicaciones del Embarazo , Efectos Tardíos de la Exposición Prenatal/tratamiento farmacológicoRESUMEN
Despite strong anti-smoking efforts, at least 12% of American women cannot quit smoking when pregnant resulting in >450,000 smoke-exposed infants born yearly. Smoking during pregnancy is the largest preventable cause of childhood respiratory illness including wheezing and asthma. Recent studies have shown a protective effect of vitamin C supplementation on the lung function of offspring exposed to in utero smoke in a non-human primate model and an initial human trial. Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP) is a randomized, double-blind, placebo-controlled trial to evaluate pulmonary function at 3months of age in infants delivered to pregnant smokers randomized to 500mg/day of vitamin C versus placebo during pregnancy. Secondary aims evaluate the incidence of wheezing through 12months and pulmonary function testing at 12months of age. Women are randomized between 13 and 23weeks gestation from clinical sites in Portland, Oregon at Oregon Health & Science University and PeaceHealth Southwest Medical Center and in Indianapolis, Indiana at Indiana University and Wishard Hospital. Vitamin C supplementation occurs from randomization to delivery. Monthly contact with participants and monitoring of medical records is performed to document medication adherence, changes in smoking and medical history, and adverse events. Pulmonary function testing of offspring occurs at 3 and 12months of age and incidence of wheezing and respiratory illness through 12months is captured via at least quarterly questionnaires. Ancillary studies are investigating the impact of vitamin C on placental blood flow and DNA methylation.
Asunto(s)
Ácido Ascórbico/administración & dosificación , Suplementos Dietéticos , Efectos Tardíos de la Exposición Prenatal/prevención & control , Prevención Primaria/métodos , Ruidos Respiratorios/efectos de los fármacos , Fumar/epidemiología , Método Doble Ciego , Femenino , Edad Gestacional , Humanos , Lactante , Embarazo , Pruebas de Función RespiratoriaRESUMEN
RATIONALE: Infants whose mothers smoked during pregnancy demonstrate lifelong decreases in pulmonary function. DNA methylation changes associated with maternal smoking during pregnancy have been described in placenta and cord blood at delivery, in fetal lung, and in buccal epithelium and blood during childhood. We demonstrated in a randomized clinical trial ( ClinicalTrials.gov identifier, NCT00632476) that vitamin C supplementation to pregnant smokers can lessen the impact of maternal smoking on offspring pulmonary function and decrease the incidence of wheeze at 1 year of age. OBJECTIVES: To determine whether vitamin C supplementation reduces changes in offspring methylation in response to maternal smoking and whether methylation at specific CpGs is also associated with respiratory outcomes. METHODS: Targeted bisulfite sequencing was performed with a subset of placentas, cord blood samples, and buccal samples collected during the NCT00632476 trial followed by independent validation of selected cord blood differentially methylated regions, using bisulfite amplicon sequencing. MEASUREMENTS AND MAIN RESULTS: The majority (69.03%) of CpGs with at least 10% methylation difference between placebo and nonsmoker groups were restored (by at least 50%) toward nonsmoker levels with vitamin C treatment. A significant proportion of restored CpGs were associated with phenotypic outcome with greater enrichment among hypomethylated CpGs. CONCLUSIONS: We identified a pattern of normalization in DNA methylation by vitamin C supplementation across multiple loci. The consistency of this pattern across tissues and time suggests a systemic and persistent effect on offspring DNA methylation. Further work is necessary to determine how genome-wide changes in DNA methylation may mediate or reflect persistent effects of maternal smoking on lung function.
Asunto(s)
Ácido Ascórbico/uso terapéutico , Metilación de ADN/efectos de los fármacos , Enfermedades del Recién Nacido/prevención & control , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/etiología , Exposición Materna/efectos adversos , Fumar/efectos adversos , Adulto , Suplementos Dietéticos , Femenino , Humanos , Lactante , Recién Nacido , Embarazo , Efectos Tardíos de la Exposición Prenatal/prevención & controlRESUMEN
IMPORTANCE: Maternal smoking during pregnancy adversely affects offspring lung development, with lifelong decreases in pulmonary function and increased asthma risk. In a primate model, vitamin C blocked some of the in-utero effects of nicotine on lung development and offspring pulmonary function. OBJECTIVE: To determine if newborns of pregnant smokers randomized to receive daily vitamin C would have improved results of pulmonary function tests (PFTs) and decreased wheezing compared with those randomized to placebo. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind trial conducted in 3 sites in the Pacific Northwest between March 2007 and January 2011. One hundred fifty-nine newborns of randomized pregnant smokers (76 vitamin C treated and 83 placebo treated) and 76 newborns of pregnant nonsmokers were studied with newborn PFTs. Follow-up assessment including wheezing was assessed through age 1 year, and PFTs were performed at age 1 year. INTERVENTIONS: Pregnant women were randomized to receive vitamin C (500 mg/d) (n = 89) or placebo (n = 90). MAIN OUTCOMES AND MEASURES: The primary outcome was measurement of newborn pulmonary function (ratio of the time to peak tidal expiratory flow to expiratory time [TPTEF:TE] and passive respiratory compliance per kilogram [Crs/kg]) within 72 hours of age. Secondary outcomes included incidence of wheezing through age 1 year and PFT results at age 1 year. A subgroup of pregnant smokers and nonsmokers had genotyping performed. RESULTS: Newborns of women randomized to vitamin C (n = 76), compared with those randomized to placebo (n = 83), had improved pulmonary function as measured by TPTEF:TE (0.383 vs 0.345 [adjusted 95% CI for difference, 0.011-0.062]; P = .006) and Crs/kg (1.32 vs 1.20 mL/cm H2O/kg [95% CI, 0.02-0.20]; P = .01). Offspring of women randomized to vitamin C had significantly decreased wheezing through age 1 year (15/70 [21%] vs 31/77 [40%]; relative risk, 0.56 [95% CI, 0.33-0.95]; P = .03). There were no significant differences in the 1-year PFT results between the vitamin C and placebo groups. The effect of maternal smoking on newborn lung function was associated with maternal genotype for the α5 nicotinic receptor (rs16969968) (P < .001 for interaction). CONCLUSIONS AND RELEVANCE: Supplemental vitamin C taken by pregnant smokers improved newborn PFT results and decreased wheezing through 1 year in the offspring. Vitamin C in pregnant smokers may be an inexpensive and simple approach to decrease the effects of smoking in pregnancy on newborn pulmonary function and respiratory morbidities. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00632476.
Asunto(s)
Ácido Ascórbico/uso terapéutico , Pulmón/fisiopatología , Ruidos Respiratorios , Fumar/efectos adversos , Vitaminas/uso terapéutico , Adulto , Suplementos Dietéticos , Método Doble Ciego , Femenino , Humanos , Lactante , Recién Nacido , Enfermedades del Recién Nacido/prevención & control , Embarazo , Atención Prenatal , Efectos Tardíos de la Exposición Prenatal/prevención & control , Pruebas de Función Respiratoria , Ruidos Respiratorios/etiología , Ruidos Respiratorios/fisiopatología , Enfermedades Respiratorias/prevención & control , Adulto JovenRESUMEN
BACKGROUND: Public interest in complementary and alternative medicine (CAM) has grown over the past decade, accompanied by increased demand for evidence-based approaches to CAM practice. In order to define the role evidence-based decision making has in CAM practice, CAM professionals must have a full understanding of evidence-based medicine (EBM) concepts. OBJECTIVE: This paper describes the design, implementation, and evaluation of a week-long intensive EBM short course for CAM faculty at a naturopathic and classical Chinese medicine institution. INTERVENTION: This 20-hour course, entitled Principles of EBM for CAM Professionals, teaches participants how to access and appraise biomedical literature, apply it to their work, and teach these concepts to their students. RESULTS: Results from precourse and postcourse evaluations suggest that, in a small group of participants, there were significant changes in EBM practice attitudes, self-appraised skills, and objectively assessed skills as a result of this course. Participants indicated they were committed to increasing their use of EBM in practice, enhancing EBM skills, using EBM in teaching, and working to change the culture at their institution to support use of EBM. At six months, 80% of participants had fully or partially followed through on their commitment to change plans.
Asunto(s)
Terapias Complementarias/educación , Medicina Basada en la Evidencia/educación , Docentes Médicos , Enseñanza , Actitud del Personal de Salud , Humanos , Medicina Tradicional China , Modelos Educacionales , Naturopatía , Oregon , Autoevaluación (Psicología)RESUMEN
BACKGROUND: The increasing use of complementary and alternative medicine (CAM) treatment is paralleled by a growing demand for an evidence-based approach to CAM practice. In 2007, the Helfgott Research Institute at the National College of Natural Medicine (NCNM), in partnership with Oregon Health & Science University (OHSU), both in Portland, OR, began a National Institutes of Health-funded initiative to increase the quality and quantity of evidence-based medicine (EBM) content in the curricula at NCNM. DESIGN: One key strategy of the Research in Complementary and Alternative Medicine Program (R-CAMP) initiative was to create a faculty development program that included four components: intensive training in EBM; professional skills enhancement; peer and mentored support; and, ultimately, utilization of these skills to incorporate EBM into the curricula. This initiative is centered on a core group of faculty at NCNM, called the Vanguard Faculty, who receives early, intensive training in EBM and works to incorporate this training into classes. Training consists of an intensive, week-long course, monthly group meetings, and periodic individualized meetings. Vanguard Faculty members also receive mentorship and access to resources to pursue individualized faculty development, research or scholarly activities. CONCLUSIONS: Early evaluations indicate that this effort has been successful in increasing EBM content in the curricula at NCNM. This article describes the Vanguard Faculty program in an effort to share the successes and challenges of implementing a wide-ranging faculty development and curricular initiative at a complementary and alternative medicine institution.
Asunto(s)
Terapias Complementarias/educación , Curriculum/normas , Medicina Basada en la Evidencia , Docentes Médicos , Humanos , National Institutes of Health (U.S.) , Oregon , Desarrollo de Personal , Estados UnidosRESUMEN
AIMS: To determine the effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) from fish on the incidence of recurrent ventricular arrhythmia in implantable cardioverter defibrillator (ICD) patients by combining results from published trials. METHODS AND RESULTS: We searched in the Medline, EMBASE, and Cochrane databases and performed a meta-analysis on all three available trials on fish oil and ventricular arrhythmia. Furthermore, we pooled individual data of two of these randomized, double-blind, placebo-controlled trials (Raitt et al. Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial. JAMA 2005;293:2884-2891 and Brouwer et al. Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA) randomized trial. JAMA 2006;295:2613-2619). The main outcome was time to first confirmed ventricular fibrillation (VF) or ventricular tachycardia (VT) combined with death for the meta-analysis, and time to first spontaneous confirmed VF or VT for the pooled analysis. The meta-analysis (n = 1148) showed no convincing protective effect of fish oil (RR 0.90; 95% CI 0.67-1.22). The hazard ratio for the subgroup of patients with coronary artery disease at baseline (0.79; 0.60-1.06) tended towards a protective effect. The pooled analysis (n = 722) showed that time to appropriate ICD intervention was similar for fish oil and placebo treatment (log-rank P = 0.79). CONCLUSION: These findings do not support a protective effect of omega-3 PUFAs from fish oil on cardiac arrhythmia in all patients with an ICD. Current data neither prove nor disprove a beneficial or a detrimental effect for subgroups of patients with specific underlying pathologies.
Asunto(s)
Desfibriladores Implantables , Ácidos Grasos Omega-3/uso terapéutico , Insuficiencia Cardíaca/prevención & control , Taquicardia Ventricular/terapia , Anciano , Suplementos Dietéticos , Femenino , Insuficiencia Cardíaca/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Prevención Secundaria , Taquicardia Ventricular/mortalidad , Resultado del TratamientoRESUMEN
BACKGROUND: Complementary and alternative medicine (CAM) use is high in people with multiple sclerosis (MS), yet there are limited reports on safety and effectiveness of CAM in MS. Naturopathic medicine encompasses a broad range of CAM modalities and may improve quality of life in patients with MS. OBJECTIVE: To assess quality of life in MS subjects who received interventions designed to "model" the "whole practice" of naturopathy. DESIGN: A pilot, randomized, controlled study with a 6-month intervention period. PARTICIPANTS: Participants who met criteria for clinically definite MS. INTERVENTIONS: The 3 intervention arms were usual care, naturopathic medicine plus usual care, and MS education plus usual care. OUTCOME MEASURES: The primary outcome measure was quality of life (36-item short form health survey [SF-36]). Secondary outcome measures included fatigue (Modified Fatigue Impact Scale); depression (Beck Depression Inventory); cognition battery (Stroop test and Paced Auditory Serial Addition Test 3), and neurologic impairment (Expanded Disability Status Scale [EDSS] and Multiple Sclerosis Functional Composite). Adverse event reporting and laboratory measures were used to assess safety. RESULTS: Forty-five (45) participants (15 per group) were randomized and all completed the 6-month intervention. There were no significant differences between groups on any outcome measure. There was a trend in favoring the naturopathic group in the General Health subscale of the SF-36 (p = 0.11), Timed Walk (p = 0.11), and neurologic impairment (EDSS) (p = 0.07). There was a trend favoring the Education group in the Stroop attention test (p = 0.07). There was no difference between groups in adverse events or laboratory changes. CONCLUSIONS: Naturopathic medicine combined with usual care for MS showed a trend in improvement in the General Health subscale of the SF-36, Timed Walk, and neurologic impairment. Evaluation of naturopathic medicine, as a multimodality regimen, warrants further investigation.
Asunto(s)
Trastornos del Conocimiento/terapia , Depresión/terapia , Fatiga/terapia , Estado de Salud , Esclerosis Múltiple/terapia , Naturopatía/métodos , Adulto , Actitud Frente a la Salud , Trastornos del Conocimiento/etiología , Depresión/etiología , Fatiga/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Proyectos Piloto , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
CONTEXT: Clinical studies of omega-3 polyunsaturated fatty acids (PUFAs) have shown a reduction in sudden cardiac death, suggesting that omega-3 PUFAs may have antiarrhythmic effects. OBJECTIVE: To determine whether omega-3 PUFAs have beneficial antiarrhythmic effects in patients with a history of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial performed at 6 US medical centers with enrollment from February 1999 until January 2003. PATIENTS: Two hundred patients with an implantable cardioverter defibrillator (ICD) and a recent episode of sustained VT or VF. INTERVENTION: Patients were randomly assigned to receive fish oil, 1.8 g/d, 72% omega-3 PUFAs, or placebo and were followed up for a median of 718 days (range, 20-828 days). MAIN OUTCOME MEASURES: Time to first episode of ICD treatment for VT/VF, changes in red blood cell concentrations of omega-3 PUFAs, frequency of recurrent VT/VF events, and predetermined subgroup analyses. RESULTS: Patients randomized to receive fish oil had an increase in the mean percentage of omega-3 PUFAs in red blood cell membranes from 4.7% to 8.3% (P<.001), with no change observed in patients receiving placebo. At 6, 12, and 24 months, 46% (SE, 5%), 51% (5%), and 65% (5%) of patients randomized to receive fish oil had ICD therapy for VT/VF compared with 36% (5%), 41% (5%), and 59% (5%) for patients randomized to receive placebo (P = .19). In the subset of 133 patients whose qualifying arrhythmia was VT, 61% (SE, 6%), 66% (6%), and 79% (6%) of patients in the fish oil group had VT/VF at 6, 12, and 24 months compared with 37% (6%), 43% (6%), and 65% (6%) of patients in the control group (P = .007). Recurrent VT/VF events were more common in patients randomized to receive fish oil (P<.001). CONCLUSION: Among patients with a recent episode of sustained ventricular arrhythmia and an ICD, fish oil supplementation does not reduce the risk of VT/VF and may be proarrhythmic in some patients.
Asunto(s)
Desfibriladores Implantables , Ácidos Grasos Omega-3/farmacología , Taquicardia Ventricular/terapia , Fibrilación Ventricular/terapia , Anciano , Suplementos Dietéticos , Método Doble Ciego , Membrana Eritrocítica/metabolismo , Ácidos Grasos Omega-3/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Riesgo , Análisis de Supervivencia , Taquicardia Ventricular/prevención & control , Fibrilación Ventricular/prevención & controlRESUMEN
OBJECTIVE: This paper describes the treatments and treatment outcome measures used by licensed naturopathic physicians in the United States who treat people with multiple sclerosis (MS). DESIGN: A cross-sectional mail survey was used. SUBJECTS: The participants were licensed naturopaths who were members of the American Association of Naturopathic Physicians. OUTCOME MEASURES: Outcome measures included practitioner demographics; patient demographics by practitioner report; recommended therapies; perceived effectiveness of treatments for MS; methods for measuring treatment effectiveness. RESULTS: Forty three percent (43%) of the respondents (166/385) had treated at least one patient with MS while 56.9% (291/385) had never treated MS. 63.3% had treated 1-10 patients with MS, 19.9% had treated 11-20 patients with MS, and 16.8% had treated > or =20 patients with MS. Among the naturopaths, 68.1% communicated with an M.D. about their patient(s)' care and the majority of patients with MS were diagnosed by an M.D. (mean % = 96.3). The mean number of therapies recommended for M.S. was 3.91 (standard deviation [SD] =2.01, range 1-10). The most frequently recommended therapies included, diet (52.4%), essential fatty acid supplementation (44.6%), vitamin/mineral supplementation (33.7%), homeopathy (30.7%), botanicals (22.3%), and antioxidants (18.1%). Respondents perceived their treatments as "very effective" for the following stages of MS: early stage (57.2%); middle stage (25.3%); and late stage (3.0%). Respondents perceived their treatments as "very effective" for the following disease-related outcomes: improved quality of life (59.0%); decrease relapse rates (48.2%); decreased symptom severity (45.8%); prevention of disease progression (41.6%). The methods used "most often" for measuring treatment effectiveness included, patient report (88.0%); physical examination (27.1%); medical records/laboratory testing (13.3%). The mean estimated percentage of patients not taking conventional disease-modifying medication was 51.2% (SD = 42.7%). CONCLUSIONS: Naturopaths use both a broad range and multiple complementary and alternative medicine CAM therapies for treating MS and report treatment effectiveness on the following outcomes: quality of life; symptom severity; relapse rates; and disease progression. Further research on single CAM therapies and holistic CAM systems is warranted in MS.
Asunto(s)
Terapias Complementarias , Concesión de Licencias , Esclerosis Múltiple/terapia , Naturopatía , Estudios Transversales , Evaluación de la Discapacidad , Encuestas Epidemiológicas , Humanos , Oregon , Evaluación de Procesos y Resultados en Atención de Salud , Resultado del TratamientoRESUMEN
BACKGROUND: Antioxidant vitamins are thought to play a role in atherosclerosis. Supplementation of these nutrients has been explored as a means of reducing cardiovascular morbidity and mortality. PURPOSE: To assess the evidence of the effectiveness of vitamin supplementation, specifically vitamins A, C, and E; beta-carotene; folic acid; antioxidant combinations; and multivitamin supplements, in preventing cardiovascular disease. DATA SOURCES: Cochrane Controlled Trials Registry and MEDLINE (1966 to September 2001), reference lists, and experts. STUDY SELECTION: The researchers selected English-language reports of randomized trials and cohort studies that assessed vitamin supplementation in western populations and reported incidence of or death from cardiovascular events. They also included reports of good- or fair-quality clinical trials of primary and secondary prevention and good- or fair-quality prospective cohort studies. Studies that examined only dietary nutrients or did not provide separate estimates for supplements were not included. DATA EXTRACTION: Two reviewers abstracted descriptive information and data on cardiovascular outcomes and mortality from included studies. The researchers assessed study quality using predetermined criteria. DATA SYNTHESIS: Evidence tables were constructed to summarize data from included studies. The researchers summarized the strength, level, and quality of the overall evidence for the effectiveness of each of the vitamin supplements in preventing or treating cardiovascular disease. CONCLUSIONS: Some good-quality cohort studies have reported an association between the use of vitamin supplements and lower risk for cardiovascular disease. Randomized, controlled trials of specific supplements, however, have failed to demonstrate a consistent or significant effect of any single vitamin or combination of vitamins on incidence of or death from cardiovascular disease. Understanding the sources of these differences will permit researchers to better analyze the cohort study data and to better design long-term clinical trials.
Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Suplementos Dietéticos , Medicina Basada en la Evidencia , Neoplasias/prevención & control , Vitaminas/uso terapéutico , Suplementos Dietéticos/efectos adversos , Humanos , Vitaminas/efectos adversosRESUMEN
A prior birth confers a strong protective effect against preeclampsia, whereas a prior abortion confers a weaker protective effect. Parous women who change partners in a subsequent pregnancy appear to lose the protective effect of a prior birth. This study (Calcium for Preeclampsia Prevention Trial, 1992-1995) examines whether nulliparous women with a prior abortion who change partners also lose the protective effect of the prior pregnancy. A cohort analysis was conducted among participants in this large clinical trial of calcium supplementation to prevent preeclampsia. Subjects were nulliparous, had one prior pregnancy or less, delivered after 20 weeks' gestation, and were interviewed at 5-21 weeks about prior pregnancies and paternity. Women without a history of abortion served as the reference group in logistic regression analyses. Women with a history of abortion who conceived again with the same partner had nearly half the risk of preeclampsia (adjusted odds ratio = 0.54, 95 percent confidence interval: 0.31, 0.97). In contrast, women with an abortion history who conceived with a new partner had the same risk of preeclampsia as women without a history of abortion (adjusted odds ratio = 1.03, 95 percent confidence interval: 0.72, 1.47). Thus, the protective effect of a prior abortion operated only among women who conceived again with the same partner. An immune-based etiologic mechanism is proposed, whereby prolonged exposure to fetal antigens from a previous pregnancy protects against preeclampsia in a subsequent pregnancy with the same father.