Eszopiclone versus zopiclone in the treatment of insomnia

OBJECTIVE: To determine the therapeutic effects of two selective GABA-A agonists, zopiclone and eszopiclone, in the treatment of insomnia. METHODS: This study comprised a phase III, single-center, randomized, double-blind, double-dummy, parallel-group, non-inferiority trial. Patients were randomized to receive zopiclone 7.5 mg or eszopiclone 3 mg, both orally, for four weeks. In total, 199 patients were evaluated during two visits and then followed for at least six weeks. The primary endpoint was the Insomnia Severity Index after four weeks of treatment. Secondary endpoints were obtained through polysomnography data, including total sleep time, sleep latency and sleep efficiency. The frequency of adverse events was also analyzed. ClinicalTrials.gov: NCT01100164. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of eszopiclone over zopiclone. Analysis of objective parameters assessed by polysomnography showed that eszopiclone increased total sleep time and also improved sleep efficiency. The safety profile of both study treatments was similar and the most common events reported in both groups were dysgeusia, headache, dizziness, irritability and nausea. Adverse events were observed in 223 patients, 109 (85.2%) in the eszopiclone group and 114 (87.7%) in the zopiclone group. CONCLUSION: Based on the Insomnia Severity Index at the end of four weeks of treatment, eszopiclone demonstrated efficacy comparable to that of zopiclone in the treatment of insomnia, increasing total sleep time as well as sleep efficiency according to polysomnography

Sildenafil improves microvascular O-2 delivery-to-utilization matching and accelerates exercise O-2 uptake kinetics in chronic heart failure

Sperandio PA, Oliveira MF, Rodrigues MK, Berton DC, Treptow E, Nery LE, Almeida DR, Neder JA. Sildenafil improves microvascular O-2 delivery-to-utilization matching and accelerates exercise O-2 uptake kinetics in chronic heart failure. Am J Physiol Heart Circ Physiol 303: H1474-H1480, 2012. First published September 28, 2012; doi:10.1152/ajpheart.00435.2012.-Nitric oxide (NO) can temporally and spatially match microvascular oxygen (O-2) delivery (QO(2mv)) to O-2 uptake (VO2) in the skeletal muscle, a crucial adjustment-to-exercise tolerance that is impaired in chronic heart failure (CHF). To investigate the effects of NO bioavailability induced by sildenafil intake on muscle QO(2mv)-to-O-2 utilization matching and VO2 kinetics, 10 males with CHF (ejection fraction = 27 +/- 6%) undertook constant work-rate exercise (70-80% peak). Breath-by-breath VO2, fractional O-2 extraction in the vastus lateralis {similar to deoxy-genated hemoglobin + myoglobin ([deoxy-Hb + Mb]) by near-infrared spectroscopy}, and cardiac output (CO) were evaluated after sildenafil (50 mg) or placebo. Sildenafil increased exercise tolerance compared with placebo by similar to 20%, an effect that was related to faster on-and off-exercise VO2 kinetics (P 0.05). On-exercise [deoxy-Hb + Mb] kinetics were slowed by sildenafil (similar to 25%), and a subsequent response overshoot (n = 8) was significantly lessened or even abolished. in contrast, [deoxy-Hb + Mb] recovery was faster with sildenafil (similar to 15%). Improvements in muscle oxygenation with sildenafil were related to faster on-exercise VO2 kinetics, blunted oscillations in ventilation (n = 9), and greater exercise capacity (P < 0.05). Sildenafil intake enhanced intramuscular QO(2mv)-to-VO2 matching with beneficial effects on VO2 kinetics and exercise tolerance in CHF. the lack of effect on CO suggests that improvement in blood flow to and within skeletal muscles underlies these effects.Universidade Federal de São Paulo, Dept Med, Div Resp Dis, Pulm Funct & Clin Exercise Physiol Unit, BR-04020050 São Paulo, BrazilQueens Univ, Dept Med, Div Resp & Crit Care Med, Kingston, ON K7L 3N6, CanadaUniversidade Federal de São Paulo, Dept Med, Div Cardiol, BR-04020050 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Div Resp Dis, Pulm Funct & Clin Exercise Physiol Unit, BR-04020050 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Div Cardiol, BR-04020050 São Paulo, BrazilWeb of Scienc

Cerebrovascular Response to Carbon Dioxide in women with Pulmonary Arterial Hypertension and Healthy Controls: implications for Sleep Disordered Breathing and Ventilatory Response

Fundamentacao: O dioxido de carbono (CO2) tem relevancia crucial no controle ventilatorio ja que alteracoes nas suas pressoes parciais influenciam o grau de estimulacao dos quimiorreceptores - particularmente os centrais - e o tonus vascular cerebral. A hipertensao arterial pulmonar (HAP) caracteriza-se por hiperventilacao alveolar e consequente hipocapnia, tanto no repouso quanto no exercicio. A hipocapnia cronica tem o potencial de instabilizar o controle ventilatorio via embotamento da reatividade cerebrovascular ao CO2 (RCVCO2). Neste contexto, o comprometimento da capacidade vasodilatadora permitiria excessiva estimulacao ventilatoria na hipercapnia e a vasoconstricao deficiente levaria a insuficiente estimulacao ventilatoria na hipocapnia. Tais anormalidades tendem a ser particularmente importantes quando as influencias humorais tem papel preponderante no controle ventilatorio, e.g., no sono e no exercicio. Portanto, torna-se licito supor que, se presente, o comprometimento da RCVCO2 seria particularmente deleterio na HAP induzindo a disturbios respiratorios do sono (DRS) e excessiva resposta ventilatoria ao CO2. Objetivos: Investigar a RCVCO2 e suas possiveis interrelacoes com os DRS e a resposta ventilatoria no repouso e no exercicio em pacientes com HAP e individuos saudaveis de mesma idade e sexo. Hipotese: A menor RCVCO2, nas pacientes com HAP, estaria associada com maior frequencia de DRS e resposta ventilatoria excessiva tanto no repouso quanto no exercicio comparativamente as controles. Metodos: A RCVCO2 foi medida em 25 pacientes do sexo feminino com HAP e 10 controles pareadas por idade. Um indice de fluxo sanguineo cerebral (IFS, Mol.l-1.s-1) foi obtido pela taxa de incremento do corante indocianina verde mensurada pela espectroscopia por raios quasi-infravermelhos (NIRO 200, Hamamatsu Inc, Japan) sobre o cortex pre-frontal. A razao entre variacoes no IFS e na PCO2 trancutanea (PCO2tc, mmHg) estimou a RCVCO2 durante dois testes em hipercapnia (CO2 3% e 5%) e dois em hipocapnia (leve e moderada). A investigacao de DRS foi realizada pela polissonografia de noite inteira e a resposta ventilatoria avaliada durante o repouso e no exercicio cardiorrespiratorio incremental em cicloergometroBV UNIFESP: Teses e dissertaçõe

Prevalence and Factors Contributing to Daytime and Nocturnal Hypoxemia in Chronic Heart Failure Patients

International audienceBackground: Despite clinical optimization, many chronic heart failure (CHF) patients remain symptomatic with dyspnea and poor quality of life. Study Objective: While oxygen therapy is prescribed in severe cases, the actual prevalence of different patterns of hypoxemia is unknown. Methods: We analyzed 183 stable CHF patients with optimized medical treatment in the “MARS” database. The patients underwent cardiorespiratory sleep recording and complete daytime pulmonary function tests including arterial blood gases. Results: This prospective cohort was predominately male (86.3%) with a mean age of 67.3 years (59.3; 75.7) and a mean BMI of 26.7 kg/m2 (23.7; 31.1). The patients were mainly in NYHA classes II and III with a mean left ventricular ejection fraction of 38%. 102 (55.61%) patients had ischemic cardiomyopathy with multiple comorbidities, and 64 (35.06%) had airflow obstruction. 8 (4.37%) patients had hypoxemia both day and night, and 151 (82.5%) had nocturnal hypoxemia only. All but 3 patients had sleep-disordered breathing (SDB), and either obstructive (59%) or central sleep apnea (39%) with a mean apnea-hypopnea index of 29.59/h (16.48; 48.27), an oxygen desaturation index of 27.09/h (14.09; 45.25), time below 90% saturation of 18 min (2; 64), and a mean nocturnal saturation of 93% (92; 94). Univariate analysis found nocturnal hypoxemia was associated with higher BMI and NT-proBNP levels. In multivariate analysis, only sleep apnea severity (p &#x3c; 0.0001) and diurnal PaO2 remained significant. Conclusion: Most stable CHF patients suffer from nocturnal hypoxemia, while daytime hypoxemia is relatively rare. The degree of nocturnal hypoxemia depends on the severity of SDB. Hypoxemia phenotyping and severity could help better evaluate the need for appropriate therapy in CHF patients

Eszopiclone versus zopiclone in the treatment of insomnia

OBJECTIVE: To determine the therapeutic effects of two selective GABA-A agonists, zopiclone and eszopiclone, in the treatment of insomnia. METHODS: This study comprised a phase III, single-center, randomized, double-blind, double-dummy, parallel-group, non-inferiority trial. Patients were randomized to receive zopiclone 7.5 mg or eszopiclone 3 mg, both orally, for four weeks. In total, 199 patients were evaluated during two visits and then followed for at least six weeks. The primary endpoint was the Insomnia Severity Index after four weeks of treatment. Secondary endpoints were obtained through polysomnography data, including total sleep time, sleep latency and sleep efficiency. The frequency of adverse events was also analyzed. ClinicalTrials.gov: NCT01100164. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of eszopiclone over zopiclone. Analysis of objective parameters assessed by polysomnography showed that eszopiclone increased total sleep time and also improved sleep efficiency. The safety profile of both study treatments was similar and the most common events reported in both groups were dysgeusia, headache, dizziness, irritability and nausea. Adverse events were observed in 223 patients, 109 (85.2%) in the eszopiclone group and 114 (87.7%) in the zopiclone group. CONCLUSION: Based on the Insomnia Severity Index at the end of four weeks of treatment, eszopiclone demonstrated efficacy comparable to that of zopiclone in the treatment of insomnia, increasing total sleep time as well as sleep efficiency according to polysomnography.Associacao Fundo de Incentivo a Pesquisa (AFIP)Universidade Federal de São Paulo (UNIFESP), Departamento de Psicobiologia, São Paulo/, SP, BrazilUniversidade Federal de São Paulo (UNIFESP), Departamento de Psicobiologia, São Paulo/, SP, BrazilWeb of Scienc

Reduction in sympathetic tone in patients with obstructive sleep apnoea: is fixed CPAP more effective than APAP? A randomised, parallel trial protocol

International audienceIntroduction Obstructive sleep apnoea (OSA) is a prevalent disease associated with cardiovascular events. Hypertension is one of the major intermediary mechanisms leading to long-term cardiovascular adverse events. Intermittent hypoxia and hypercapnia associated with nocturnal respiratory events stimulate chemoreflexes, resulting in sympathetic overactivity and blood pressure (BP) elevation. Continuous positive airway pressure (CPAP) is the primary treatment for OSA and induces a small but significant reduction in BP. The use of auto-adjusting positive airway pressure (APAP) has increased in the last years and studies showed different ranges of BP reduction when comparing both modalities. However, the pathophysiological mechanisms implicated are not fully elucidated. Variations in pressure through the night inherent to APAP may induce persistent respiratory efforts and sleep fragmentation that might impair sympathovagal balance during sleep and result in smaller decreases in BP. Therefore, this double-blind randomised controlled trial aims to compare muscle sympathetic nerve activity (MSNA) assessed by microneurography (reference method for measuring sympathetic activity) after 1 month of APAP versus fixed CPAP in treatment-naive OSA patients. This present manuscript describes the design of our study, no results are presented herein. and is registered under the below reference number. Methods and analysis Adult subjects with newly diagnosed OSA (Apnoea–Hypopnoea Index >20/hour) will be randomised for treatment with APAP or fixed CPAP. Measurements of sympathetic activity by MSNA, heart rate variability and catecholamines will be obtained at baseline and after 30 days. The primary composite outcome will be the change in sympathetic tone measured by MSNA in bursts/min and bursts/100 heartbeats. Sample size calculation was performed with bilateral assumption. We will use the Student’s t-test to compare changes in sympathetic tone between groups. Ethics and dissemination The protocol was approved by The French Regional Ethics Committee. The study started in March 2018 with primary completion expected to March 2019. Dissemination plans of the results include presentations at conferences and publication in peer-reviewed journals. Trial registration number NCT03428516 ; Pre-results