RESUMEN
OBJECTIVE: Many short-term studies indicate that 5% weight loss in the obese is enough to induce significant improvements of cardiovascular risk factors. However, it is not known what degree of weight loss is required to improve risk factors over a more extended period of time or how ageing and secular trends per se are influencing risk factors during long-term follow-up. METHODS: Patients examined after 10 years in the intervention study Swedish Obese Subjects were used for the current analysis. Surgically treated subjects (n=959) and conventionally treated obese controls (n=842) were pooled to obtain a study group with a large range of weight changes. The patients were divided in 11 groups based on the amount of weight change. Analysis of covariance was used to determine the necessary weight change over 10 years for a significant alteration of a risk factor. In a linear regression of risk factor change by weight change, the y intercept was interpreted as the effect of 10 years ageing and secular trends on a given risk factor in the absence of weight change. RESULTS: The necessary weight loss for significant improvement of risk factors ranged from 10 to 44 kg. At zero weight change, 10 years of ageing was associated with significant increases in systolic blood pressure, pulse pressure, high-density lipoprotein cholesterol and glucose, and with significant decreases in diastolic blood pressure, total cholesterol, triglycerides and insulin. CONCLUSIONS: The necessary weight loss to maintain a favourable effect on risk factors in an obese population is larger than previously indicated by short-term studies. Treatment effects are influenced by non-weight change-dependant shifts in risk factor levels.
Asunto(s)
Envejecimiento , Enfermedades Cardiovasculares/fisiopatología , Obesidad/fisiopatología , Pérdida de Peso , Análisis de Varianza , Biomarcadores , Glucemia/metabolismo , Índice de Masa Corporal , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/terapia , Dieta , Femenino , Estudios de Seguimiento , Humanos , Modelos Lineales , Lipoproteínas HDL/sangre , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/terapia , Factores de Riesgo , Suecia/epidemiología , Triglicéridos/sangreRESUMEN
Whilst recent large-scale studies have provided much evidence on the natural history and therapeutic response in patients with chronic obstructive pulmonary disease (COPD), relatively little is known about the effect in younger patients. We report a pre-specified post-hoc analysis of 356 patients with COPD ≤ 50 years old from the four year randomised, double blind placebo controlled Understanding Potential Long Term Impact on Function with Tiotropium (UPLIFT) trial. Inclusion criteria included a post-bronchodilator forced expiratory volume in 1 s (FEV(1)) of ≤70%, FEV(1)/FVC < 0.70, age ≥40 years, and smoking history of ≥10 pack years. Younger patients had a mean FEV(1) of 1.24 L (39% predicted) and an impaired health-related quality of life (St. George's Respiratory Questionnaire (SGRQ)) compared to the entire UPLIFT population. There were 40.2% women and 51.1% current smokers in the younger age group. Tiotropium was associated with a sustained improvement in spirometry and SGRQ. Mean decline in post-bronchodilator FEV(1) was 58 ml/year (placebo) vs. 38 ml/year (tiotropium) (p = 0.01). Corresponding values for pre-bronchodilator FEV(1) were 41 ml/year (placebo) compared with 34 ml/year (tiotropium) (p = 0.34). The hazard ratio (95%CI) for an exacerbation in the younger age group was 0.87(0.68, 1.13)). The rate of exacerbations was reduced by tiotropium (rate ratio (95%CI) = 0.73(0.56, 0.95)). Tiotropium resulted in sustained bronchodilation, improved quality of life, and a decreased exacerbation rate in younger patients. Tiotropium also resulted in a significant reduction in the decline in post-bronchodilator FEV(1), suggesting possible disease modification by tiotropium in younger patients with COPD.
Asunto(s)
Broncodilatadores/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Derivados de Escopolamina/uso terapéutico , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Volumen Espiratorio Forzado/fisiología , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Calidad de Vida , Encuestas y Cuestionarios , Bromuro de Tiotropio , Resultado del TratamientoRESUMEN
AIMS: Animal studies indicate a role for 11beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) in the development of obesity. The association to glucose homeostasis is less clear. We investigated the relationship between HSD11B1 mRNA levels in adipose tissue and in skeletal muscle and anthropometric and metabolic measurements in humans with and without impaired glucose homeostasis. METHODS: Twelve obese subjects with impaired glucose homeostasis (MetS+) and 12 obese controls (MetS-) received a Very Low Calorie Diet for 16 weeks and adipose tissue biopsies, blood samples and measurements were obtained. In a second cohort, skeletal muscle biopsies, blood samples and measurements were obtained from 18 subjects with type 2 diabetes (T2DM) and 17 subjects with normal glucose tolerance (NGT). Gene expression was measured by DNA microarray in both studies. RESULTS: HSD11B1 mRNA levels were reduced during diet, and anthropometric measurements and metabolic parameters were associated with HSD11B1 mRNA levels in the MetS- group. However, in the MetS+ group these associations were lost or in opposite direction. This difference was also observed in skeletal muscle between T2DM and NGT. CONCLUSIONS: HSD11B1 mRNA levels are associated with metabolic parameters and anthropometric measurements in subjects with normal glucose homeostasis but not in subjects with impaired glucose homeostasis.
Asunto(s)
Tejido Adiposo/patología , Diabetes Mellitus Tipo 2/metabolismo , Intolerancia a la Glucosa/metabolismo , Músculo Esquelético/patología , Obesidad/complicaciones , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/genética , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/metabolismo , Tejido Adiposo/metabolismo , Antropometría , Biomarcadores/metabolismo , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patología , Femenino , Perfilación de la Expresión Génica , Intolerancia a la Glucosa/genética , Intolerancia a la Glucosa/patología , Prueba de Tolerancia a la Glucosa , Homeostasis , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
The aim of the present study was investigate the long-term effect of tiotropium as first maintenance respiratory medication in chronic obstructive pulmonary disease (COPD). A 4-yr, randomised, multicentre, double-blind, parallel-group, placebo-controlled trial (Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT) was conducted. Analysis focused on the effect of tiotropium versus matching placebo in the 810 (13.5%) COPD patients not on other maintenance treatment (long-acting beta-agonists, inhaled corticosteroids, theophyllines or anticholinergics) at randomisation. Spirometry, health-related quality of life (St George's Respiratory Questionnaire (SGRQ) score), exacerbations of COPD and mortality were also analysed. 403 patients (mean+/-sd age 63+/-8 yrs, post-bronchodilator forced expiratory volume in 1 s (FEV(1)) 53+/-12% predicted) received tiotropium and 407 (64+/-8 yrs of age, post-bronchodilator FEV(1) 51+/-12% pred) received placebo. Post-bronchodilator FEV(1) decline was 42+/-4 mL.yr(-1) in the tiotropium group and 53+/-4 mL.yr(-1) in the placebo group (p = 0.026). At 48 months, the morning pre-dose FEV(1) was 134 mL higher in the tiotropium group compared to the placebo group (p<0.001). SGRQ total score declined more slowly in the tiotropium group (difference of 1.05+/-0.34 units.yr(-1); p = 0.002). This was particularly significant for the impact (difference of 1.08+/-0.37 units.yr(-1); p = 0.004) and activity (1.44+/-0.40 units.yr(-1); p<0.001) domains, but not for symptoms (0.26+/-0.50 units.yr(-1); p = 0.6). At 48 months, the difference in total score was 4.6 units (p<0.001) with tiotropium compared to placebo. In patients with COPD who are not on maintenance therapy, tiotropium is associated with significant benefits in disease progression.
Asunto(s)
Broncodilatadores/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Derivados de Escopolamina/uso terapéutico , Corticoesteroides/uso terapéutico , Agonistas Adrenérgicos beta/uso terapéutico , Anciano , Antagonistas Colinérgicos/uso terapéutico , Progresión de la Enfermedad , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Calidad de Vida , Espirometría , Teofilina/uso terapéutico , Tiempo , Bromuro de TiotropioRESUMEN
UPLIFT (Understanding Potential Long-Term Improvements in Function with Tiotropium), a 4-yr trial of tiotropium in chronic obstructive pulmonary disease, allowed for assessment of smoking status on long-term responses to maintenance bronchodilator therapy. 5,993 patients were randomised (tiotropium/placebo). Lung function, St George's Respiratory Questionnaire, exacerbations and adverse events were followed. Patients were characterised as continuing smokers (CS), continuing ex-smokers (CE), or intermittent smokers (IS) based on self-reporting smoking behaviour. 60%, 14% and 26% of patients were CE, CS and IS, respectively. The rate of forced expiratory volume in 1 s (FEV(1)) decline for placebo patients was most rapid in CS (-52+/-4, -37+/2 and -23+/2 mL.yr(-1) in CS, IS, and CE, respectively). Tiotropium did not alter FEV(1) decline, but was associated with significant improvements in pre- and post-bronchodilator FEV(1) over placebo that persisted throughout the 4-yr trial for each smoking status (pre-bronchodilator: 127, 55 and 97 mL at 48 months in CS, IS and CE, respectively; p< or =0.0003). Tiotropium reduced exacerbation risk in CS (HR (95% CI) 0.80 (0.67-0.95)), in CE (0.85 (0.79-0.92)) and trended towards significance in IS (0.89 (0.79-1.00)). At 4 yrs, St George's Respiratory Questionnaire for tiotropium patients improved the most in CS (-4.63 units, p = 0.0006) and the least in IS (-0.60 units, p = 0.51), [corrected] compared with control. Tiotropium provided long-term benefits irrespective of smoking status, although differences among categories were observed.
Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica/terapia , Derivados de Escopolamina/uso terapéutico , Fumar , Anciano , Broncodilatadores/uso terapéutico , Antagonistas Colinérgicos/farmacología , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Placebos , Calidad de Vida , Factores de Tiempo , Bromuro de Tiotropio , Resultado del TratamientoRESUMEN
BACKGROUND: Given that carotid artery stenosis (CAS) intervention is procedurally difficult, possesses an extensive learning curve, and involves a grave list of potential complications, construct validation of new non-clinical training devices is of increasing importance. PURPOSE: To evaluate the construct validity of the Procedicus-Virtual Interventional Simulator Trainer (Procedicus-VIST) and its use as a training tool. MATERIAL AND METHODS: Sixteen interventionalists (15 males, one female; mean interventional radiology [IR] experience >11 years) and 16 medical students (15 males, one female; no IR experience) received 1 hour of didactic instruction followed by an hour of familiarization training. Subjects then attempted to complete a carotid artery stenting procedure within 1 hour while their performance metrics were recorded. All participants completed a qualitative exit survey of subjective parameters using a visual analog scale. RESULTS: Procedure and fluoroscopic time was 8.7 and 8.7 min greater in the novice group (P=0.0066 and P=0.0031), respectively. There were no significant differences in performances between the two groups in the remaining metrics of cine loops (number recorded), tool/vessel ratio, coverage percentage, and placement accuracy or residual stenosis. Contrast measurement metrics were found to be too imprecise for statistical analysis. Experienced and novice opinions differed significantly for six of 10 subjective parameters. No statistically significant difference in video-gaming habits was demonstrated. CONCLUSION: With the exception of the metrics of performance time and fluoroscopic use, construct validity of the Procedicus-VIST carotid metrics were not confirmed. Virtual reality simulation as a training method was valued more by novices than by experienced interventionalists.