Diagnosis and study of rare heart diseases: multimodality – left ventricular non-compaction cardiomyopathy

La miocardiopatía no compactada del ventrículo izquierdo descrita a principios del siglo XX en especímenes patológicos, fue considerada de baja prevalencia hasta los años 80 cuando se diagnosticó in vivo. Más recientemente, con el advenimiento de nuevas técnicas en ecocardiografía y resonancia cardiaca, se diagnostica con más frecuencia. El ventrículo más comprometido es el izquierdo, pero puede incluir también el ventrículo derecho o ambos. El nombre de miocardiopatía no compactada del ventrículo izquierdo obedece a que el miocardio presenta una capa delgada de ventrículo compacto y otra capa de trabéculas con recesos intertrabeculares profundos (Miocardio no compacto) principalmente a nivel de la pared lateral y el ápex, característica que tanto en ecocardiografía, como en resonancia cardiaca es la base para determinar el diagnóstico, tomando como criterio la relación entre el miocardio no compacto y el miocardio compacto. El realce tardío con gadolinio en resonancia ayuda a identificar la fibrosis, que tiene importancia pronóstica. Se describen varios tipos fenotípicos que guardan relación igualmente con el pronóstico de la enfermedad. Las arritmias, la falla cardiaca, la muerte súbita o la embolia de origen cardiaco son las formas de presentación que más se relacionan con la miocardiopatía no copactada del ventrículo izquierdo.Left ventricular non-compaction cardiomyopathy, described at the beginning of the 20th century, was considered to be of low prevalence until the 1980's, when it was disgnosed in vivo. More recently, with the advent of new echocardiography and cardiac resonance techniques, it is diagnosed more frequently. The left ventricle is the most compromised, but the right, or both, can also be affected. The name of left ventricular non-compaction cardiomyopathy refers to myocardium has a thin layer of compacted and another layer of trabeculae with deep intra-trabecular recesses (non-compacted myocardium), mainly at the level of the lateral wall and the apex. This is a characteristic that is the basis for determining the diagnosis both in echocardiography and cardiac resonance, with the relationship between the non-compacted myocardium and the compacted myocardium. Late gadolinium enhancement in magnetic resonance helps to identify the fibrosis, which has prognostic importance. Various phenotypes have ben decribed that maintain the relationship with the prognosis of the disease. The arrhythmias, heart failure, sudden death, or emboli of cardiac origin are the forms that are more associated with left ventricular non-compaction cardiomyopathy

Efficacy and safety characteristics of mometasone furoate/formoterol fumarate fixed-dose combination in subjects with moderate to very severe COPD: findings from pooled analysis of two randomized, 52-week placebo-controlled trials

Background: The clinical efficacy and safety of a mometasone furoate/formoterol fumarate (MF/F) fixed-dose combination formulation administered via a metered-dose inhaler was investigated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). Methods: Two 52-week, multicenter, double-blind, placebo-controlled trials with identical study designs were conducted in current or ex-smokers (aged =40 years), and pooled study results are presented herein. Subjects (n = 2251) were randomized to 26 weeks of twice-daily treatment with MF/F 400/10 µg, MF/F 200/10 µg, MF 400 µg, F 10 µg, or placebo. After the 26-week treatment period, placebo subjects completed the trial and 75% of subjects on active treatment entered a 26-week safety extension. Coprimary efficacy variables were mean changes in forced expiratory volume in one second (FEV1), area under the curve from 0 to 12 hours postdose (AUC0–12 h), and morning predose/trough FEV1 from baseline to the week 13 endpoint. Key secondary efficacy variables were St George’s Respiratory Questionnaire scores, symptom-free nights, time-to-first exacerbation, and partly stable COPD at the week 26 endpoint. Results: In the 26-week treatment period, significantly greater increases in FEV1 AUC0–12 h occurred with MF/F 400/10 versus MF 400 and placebo at the week 13 and week 26 endpoints (P = 0.032). These increases were over three-fold greater with MF/F 400/10 than with MF 400. Also, significantly greater increases in morning predose/trough FEV1 occurred with MF/F 400/10 versus F 10 and placebo at the week 13 endpoint (P \u3c 0.05). The increase was four-fold greater with MF/F 400/10 than with F 10. All active treatment groups achieved minimum clinically important differences from baseline (\u3e4 units) in St George’s Respiratory Questionnaire scores at week 26. Symptom-free nights increased by =14% in the MF/F 400/10, MF 400, and F 10 groups (P= 0.033 versus placebo). The incidence of exacerbations was lower in the MF/F groups (=33.3%) than it was in the MF, formoterol, and placebo groups (=33.8%) over the 26-week treatment period. The incidence of adverse events was similar in the active-treated and placebo-treated subjects across 26 weeks of treatment. Over the 1-year study period, there were no notable differences in the incidence or types of adverse events between the MF/F 400/10 and MF/F 200/10 groups compared with the MF or formoterol groups. Differences in rates of individual treatment-emergent adverse events were Conclusion: Patients treated with MF/F demonstrated significant improvements in lung function, health status, and exacerbation rates. Although significant improvements were seen with both doses, a trend showing a dose-response effect was observed in the lung function measurements

Long-acting beta2-agonists for chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a respiratory disease that causes progressive symptoms of breathlessness, cough and mucus build-up. It is the fourth or fifth most common cause of death worldwide and is associated with significant healthcare costs.Inhaled long-acting beta2-agonists (LABAs) are widely prescribed to manage the symptoms of COPD when short-acting agents alone are no longer sufficient. Twice-daily treatment with an inhaled LABA is aimed at relieving symptoms, improving exercise tolerance and quality of life, slowing decline and even improving lung function and preventing and treating exacerbations. OBJECTIVES: To assess the effects of twice-daily long-acting beta2-agonists compared with placebo for patients with COPD on the basis of clinically important endpoints, primarily quality of life and COPD exacerbations. SEARCH METHODS: We searched the Cochrane Airways Group trials register, ClinicalTrials.gov and manufacturers' websites in June 2013. SELECTION CRITERIA: Parallel, randomised controlled trials (RCTs) recruiting populations of patients with chronic obstructive pulmonary disease. Studies were required to be at least 12 weeks in duration and designed to assess the safety and efficacy of a long-acting beta2-agonist against placebo. DATA COLLECTION AND ANALYSIS: Data and characteristics were extracted independently by two review authors, and each study was assessed for potential sources of bias. Data for all outcomes were pooled and subgrouped by LABA agent (formoterol 12 μg, formoterol 24 μg and salmeterol 50 μg) and then were separately analysed by LABA agent and subgrouped by trial duration. Sensitivity analyses were conducted for the proportion of participants taking inhaled corticosteroids and for studies with high or uneven rates of attrition. MAIN RESULTS: Twenty-six RCTs met the inclusion criteria, randomly assigning 14,939 people with COPD to receive twice-daily LABA or placebo. Study duration ranged from three months to three years; the median duration was six months. Participants were more often male with moderate to severe symptoms at randomisation; mean forced expiratory volume in 1 second (FEV1) was between 33% and 55% predicted normal in the studies, and mean St George's Respiratory Questionnaire score (SGRQ) ranged from 44 to 55 when reported.Moderate-quality evidence showed that LABA treatment improved quality of life on the SGRQ (mean difference (MD) -2.32, 95% confidence interval (CI) -3.09 to -1.54; I(2) = 50%; 17 trials including 11,397 people) and reduced the number of exacerbations requiring hospitalisation (odds ratio (OR) 0.73, 95% CI 0.56 to 0.95; I(2) = 10%; seven trials including 3804 people). In absolute terms, 18 fewer people per 1000 were hospitalised as the result of an exacerbation while receiving LABA therapy over a weighted mean of 7 months (95% CI 3 to 31 fewer). Scores were also improved on the Chronic Respiratory Disease Questionnaire (CRQ), and more people receiving LABA treatment showed clinically important improvement of at least four points on the SGRQ.The number of people who had exacerbations requiring a course of oral steroids or antibiotics was also lower among those taking LABA (52 fewer per 1000 treated over 8 months; 95% CI 24 to 78 fewer, moderate quality evidence).Mortality was low, and combined findings of all studies showed that LABA therapy did not significantly affect mortality (OR 0.90, 95% CI 0.75 to 1.08; I(2) = 21%; 23 trials including 14,079 people, moderate quality evidence). LABA therapy did not affect the rate of serious adverse events (OR 0.97, 95% CI 0.83 to 1.14; I(2) = 34%, moderate quality evidence), although there was significant unexplained heterogeneity, especially between the two formoterol doses.LABA therapy improved predose FEV1 by 73 mL more than placebo (95% CI 48 to 98; I(2) = 71%, low quality evidence), and people were more likely to withdraw from placebo than from LABA therapy (OR 0.74, 95% CI 0.69 to 0.80; I(2) = 0%). Higher rates of withdrawal in the placebo arm may reduce our confidence in some results, but the disparity is more likely to reduce the magnitude of difference between LABA and placebo than inflate the true effect; removing studies at highest risk of bias on the basis of high and unbalanced attrition did not change conclusions for the primary outcomes. AUTHORS' CONCLUSIONS: Moderate-quality evidence from 26 studies showed that inhaled long-acting beta2-agonists are effective over the medium and long term for patients with moderate to severe COPD. Their use is associated with improved quality of life and reduced exacerbations, including those requiring hospitalisation. Overall, findings showed that inhaled LABAs did not significantly reduce mortality or serious adverse events

Long-acting inhaled therapy (beta-agonists, anticholinergics and steroids) for COPD: a network meta-analysis.

BACKGROUND: Pharmacological therapy for chronic obstructive pulmonary disease (COPD) is aimed at relieving symptoms, improving quality of life and preventing or treating exacerbations.Treatment tends to begin with one inhaler, and additional therapies are introduced as necessary. For persistent or worsening symptoms, long-acting inhaled therapies taken once or twice daily are preferred over short-acting inhalers. Several Cochrane reviews have looked at the risks and benefits of specific long-acting inhaled therapies compared with placebo or other treatments. However for patients and clinicians, it is important to understand the merits of these treatments relative to each other, and whether a particular class of inhaled therapies is more beneficial than the others. OBJECTIVES: To assess the efficacy of treatment options for patients whose chronic obstructive pulmonary disease cannot be controlled by short-acting therapies alone. The review will not look at combination therapies usually considered later in the course of the disease.As part of this network meta-analysis, we will address the following issues.1. How does long-term efficacy compare between different pharmacological treatments for COPD?2. Are there limitations in the current evidence base that may compromise the conclusions drawn by this network meta-analysis? If so, what are the implications for future research? SEARCH METHODS: We identified randomised controlled trials (RCTs) in existing Cochrane reviews by searching the Cochrane Database of Systematic Reviews (CDSR). In addition, we ran a comprehensive citation search on the Cochrane Airways Group Register of trials (CAGR) and checked manufacturer websites and reference lists of other reviews. The most recent searches were conducted in September 2013. SELECTION CRITERIA: We included parallel-group RCTs of at least 6 months' duration recruiting people with COPD. Studies were included if they compared any of the following treatments versus any other: long-acting beta2-agonists (LABAs; formoterol, indacaterol, salmeterol); long-acting muscarinic antagonists (LAMAs; aclidinium, glycopyrronium, tiotropium); inhaled corticosteroids (ICSs; budesonide, fluticasone, mometasone); combination long-acting beta2-agonist (LABA) and inhaled corticosteroid (LABA/ICS) (formoterol/budesonide, formoterol/mometasone, salmeterol/fluticasone); and placebo. DATA COLLECTION AND ANALYSIS: We conducted a network meta-analysis using Markov chain Monte Carlo methods for two efficacy outcomes: St George's Respiratory Questionnaire (SGRQ) total score and trough forced expiratory volume in one second (FEV1). We modelled the relative effectiveness of any two treatments as a function of each treatment relative to the reference treatment (placebo). We assumed that treatment effects were similar within treatment classes (LAMA, LABA, ICS, LABA/ICS). We present estimates of class effects, variability between treatments within each class and individual treatment effects compared with every other.To justify the analyses, we assessed the trials for clinical and methodological transitivity across comparisons. We tested the robustness of our analyses by performing sensitivity analyses for lack of blinding and by considering six- and 12-month data separately. MAIN RESULTS: We identified 71 RCTs randomly assigning 73,062 people with COPD to 184 treatment arms of interest. Trials were similar with regards to methodology, inclusion and exclusion criteria and key baseline characteristics. Participants were more often male, aged in their mid sixties, with FEV1 predicted normal between 40% and 50% and with substantial smoking histories (40+ pack-years). The risk of bias was generally low, although missing information made it hard to judge risk of selection bias and selective outcome reporting. Fixed effects were used for SGRQ analyses, and random effects for Trough FEV1 analyses, based on model fit statistics and deviance information criteria (DIC). SGRQ SGRQ data were available in 42 studies (n = 54,613). At six months, 39 pairwise comparisons were made between 18 treatments in 25 studies (n = 27,024). Combination LABA/ICS was the highest ranked intervention, with a mean improvement over placebo of -3.89 units at six months (95% credible interval (CrI) -4.70 to -2.97) and -3.60 at 12 months (95% CrI -4.63 to -2.34). LAMAs and LABAs were ranked second and third at six months, with mean differences of -2.63 (95% CrI -3.53 to -1.97) and -2.29 (95% CrI -3.18 to -1.53), respectively. Inhaled corticosteroids were ranked fourth (MD -2.00, 95% CrI -3.06 to -0.87). Class differences between LABA, LAMA and ICS were less prominent at 12 months. Indacaterol and aclidinium were ranked somewhat higher than other members of their classes, and formoterol 12 mcg, budesonide 400 mcg and formoterol/mometasone combination were ranked lower within their classes. There was considerable overlap in credible intervals and rankings for both classes and individual treatments. Trough FEV1 Trough FEV1 data were available in 46 studies (n = 47,409). At six months, 41 pairwise comparisons were made between 20 treatments in 31 studies (n = 29,271). As for SGRQ, combination LABA/ICS was the highest ranked class, with a mean improvement over placebo of 133.3 mL at six months (95% CrI 100.6 to 164.0) and slightly less at 12 months (mean difference (MD) 100, 95% CrI 55.5 to 140.1). LAMAs (MD 103.5, 95% CrI 81.8 to 124.9) and LABAs (MD 99.4, 95% CrI 72.0 to 127.8) showed roughly equivalent results at six months, and ICSs were the fourth ranked class (MD 65.4, 95% CrI 33.1 to 96.9). As with SGRQ, initial differences between classes were not so prominent at 12 months. Indacaterol and salmeterol/fluticasone were ranked slightly better than others in their class, and formoterol 12, aclidinium, budesonide and formoterol/budesonide combination were ranked lower within their classes. All credible intervals for individual rankings were wide. AUTHORS' CONCLUSIONS: This network meta-analysis compares four different classes of long-acting inhalers for people with COPD who need more than short-acting bronchodilators. Quality of life and lung function were improved most on combination inhalers (LABA and ICS) and least on ICS alone at 6 and at 12 months. Overall LAMA and LABA inhalers had similar effects, particularly at 12 months. The network has demonstrated the benefit of ICS when added to LABA for these outcomes in participants who largely had an FEV1 that was less than 50% predicted, but the additional expense of combination inhalers and any potential for increased adverse events (which has been established by other reviews) require consideration. Our findings are in keeping with current National Institute for Health and Care Excellence (NICE) guidelines

Diagnosis and study of rare heart diseases: multimodality – left ventricular non-compaction cardiomyopathy

La miocardiopatía no compactada del ventrículo izquierdo descrita a principios del siglo XX en especímenes patológicos, fue considerada de baja prevalencia hasta los años 80 cuando se diagnosticó in vivo. Más recientemente, con el advenimiento de nuevas técnicas en ecocardiografía y resonancia cardiaca, se diagnostica con más frecuencia. El ventrículo más comprometido es el izquierdo, pero puede incluir también el ventrículo derecho o ambos. El nombre de miocardiopatía no compactada del ventrículo izquierdo obedece a que el miocardio presenta una capa delgada de ventrículo compacto y otra capa de trabéculas con recesos intertrabeculares profundos (Miocardio no compacto) principalmente a nivel de la pared lateral y el ápex, característica que tanto en ecocardiografía, como en resonancia cardiaca es la base para determinar el diagnóstico, tomando como criterio la relación entre el miocardio no compacto y el miocardio compacto. El realce tardío con gadolinio en resonancia ayuda a identificar la fibrosis, que tiene importancia pronóstica. Se describen varios tipos fenotípicos que guardan relación igualmente con el pronóstico de la enfermedad. Las arritmias, la falla cardiaca, la muerte súbita o la embolia de origen cardiaco son las formas de presentación que más se relacionan con la miocardiopatía no copactada del ventrículo izquierdo.Left ventricular non-compaction cardiomyopathy, described at the beginning of the 20th century, was considered to be of low prevalence until the 1980's, when it was disgnosed in vivo. More recently, with the advent of new echocardiography and cardiac resonance techniques, it is diagnosed more frequently. The left ventricle is the most compromised, but the right, or both, can also be affected. The name of left ventricular non-compaction cardiomyopathy refers to myocardium has a thin layer of compacted and another layer of trabeculae with deep intra-trabecular recesses (non-compacted myocardium), mainly at the level of the lateral wall and the apex. This is a characteristic that is the basis for determining the diagnosis both in echocardiography and cardiac resonance, with the relationship between the non-compacted myocardium and the compacted myocardium. Late gadolinium enhancement in magnetic resonance helps to identify the fibrosis, which has prognostic importance. Various phenotypes have ben decribed that maintain the relationship with the prognosis of the disease. The arrhythmias, heart failure, sudden death, or emboli of cardiac origin are the forms that are more associated with left ventricular non-compaction cardiomyopathy

Análisis del sector de chocolate de mesa en Santafé de Bogotá y estudio para la introducción de una nueva marca, caso: Chocolate campesino

La Compañía Occidental de Chocolates es una empresa dedicada a la producción de Chocolate de mesa el cual comercializa en los departamentos de Huila, Tolima, Caqueta y Meta. Su producto “Chocolate Campesino' es un producto 100% natura

Análisis del sector de chocolate de mesa en Santafé de Bogotá y estudio para la introducción de una nueva marca, caso: Chocolate campesino

" La Compañía Occidental de Chocolates es una empresa dedicada a la producción de Chocolate de mesa el cual comercializa en los departamentos de Huila, Tolima, Caqueta y Meta. Su producto “Chocolate Campesino"" es un producto 100% natural

Efficacy and safety of a fixed-dose combination of mometasone furoate and formoterol fumarate in subjects with moderate to very severe COPD: results from a 52-week Phase III trial

Donald P Tashkin1, Dennis E Doherty2, Edward Kerwin3, Carlos E Matiz-Bueno4, Barbara Knorr5, Tulin Shekar5, Sibabrata Banerjee5, Heribert Staudinger51David Geffen School of Medicine at UCLA, Los Angeles, CA, 2Division of Pulmonary, Critical Care, and Sleep Medicine, University of Kentucky, Lexington, KY, 3Clinical Research Institute of Southern Oregon, Medford, OR USA; 4Fundación Salud Bosque, Bogota, Colombia; 5Merck Sharp & Dohme Corp, Whitehouse Station, NJ USABackground: A clinical trial of mometasone furoate/formoterol fumarate (MF/F) administered via a metered-dose inhaler in subjects with moderate to very severe chronic obstructive pulmonary disease (COPD) investigated the efficacy and safety of a fixed-dose combination of MF/F.Methods: This multicenter, double-blind, placebo-controlled trial had a 26-week treatment period and a 26-week safety extension. Subjects (n = 1055; ≥40 years) were current or ex-smokers randomized to twice-daily treatment with inhaled MF/F 400/10 µg, MF/F 200/10 µg, MF 400 µg, F 10 µg, or placebo. The coprimary endpoints of the trial were mean changes from baseline in forced expiratory volume in 1 second (FEV1) over 0–12 hours (AUC0–12 FEV1) with MF/F versus MF, and in morning predose FEV1 with MF/F versus F. Key secondary endpoints were quality of life (Saint George’s Respiratory Questionnaire [SGRQ]), symptom-free nights, and partly stable COPD at 26 weeks, as well as time to first COPD exacerbation.Results: Significant improvements in FEV1 AUC0–12 occurred at endpoint with MF/F 400/10 and MF/F 200/10 versus MF 400 (P ≤ 0.007). Significant bronchodilation occurred in 5 minutes with MF/F, and serial spirometry demonstrated sustained FEV1 improvements with MF/F over the treatment period. Significant improvements in morning predose FEV1 occurred with both MF/F doses, and these effects were further investigated by excluding results for subjects whose morning FEV1 data were collected >2 days after the last dose of study treatment. Improvements in SGRQ total scores surpassed the minimum clinically important difference of at least 4 units with MF/F 400/10. MF/F 400/10 significantly reduced the time-to-first COPD exacerbation. Similar proportions of subjects in all five treatment groups reported treatment-emergent adverse events. Rates of pneumonia were low (≤1.0%) across treatment groups.Conclusion: MF/F 400/10 µg twice daily was shown to be an effective therapy for patients with moderate to very severe COPD, and both MF/F 400/10 µg twice daily and MF/F 200/10 µg twice daily were well tolerated.Keywords: chronic obstructive pulmonary disease, FEV1, spirometry, exacerbation, inhaled corticosteroid, bronchodilato