Risk factors associated with mortality among elderly patients with COVID-19: Data from 55 intensive care units in Spain.

INTRODUCTION AND OBJECTIVES: Critically-ill elderly ICU patients with COVID-19 have poor outcomes. We aimed to compare the rates of in-hospital mortality between non-elderly and elderly critically-ill COVID-19 ventilated patients, as well as to analyze the characteristics, secondary outcomes and independent risk factors associated with in-hospital mortality of elderly ventilated patients. PATIENTS AND METHODS: We conducted a multicentre, observational cohort study including consecutive critically-ill patients admitted to 55 Spanish ICUs due to severe COVID-19 requiring mechanical ventilation (non-invasive respiratory support [NIRS; include non-invasive mechanical ventilation and high-flow nasal cannula] and invasive mechanical ventilation [IMV]) between February 2020 and October 2021. RESULTS: Out of 5,090 critically-ill ventilated patients, 1,525 (27%) were aged ≥70 years (554 [36%] received NIRS and 971 [64%] received IMV. In the elderly group, median age was 74 years (interquartile range 72-77) and 68% were male. Overall in-hospital mortality was 31% (23% in patients <70 years and 50% in those ≥70 years; p<0.001). In-hospital mortality in the group ≥70 years significantly varied according to the modality of ventilation (40% in NIRS vs. 55% in IMV group; p<0.001). Factors independently associated with in-hospital mortality in elderly ventilated patients were age (sHR 1.07 [95%CI 1.05-1.10], p<0.001); previous admission within the last 30 days (sHR 1.40 [95%CI 1.04-1.89], p = 0.027); chronic heart disease (sHR 1.21 [95%CI 1.01-1.44], p = 0.041); chronic renal failure (sHR 1.43 [95%CI 1.12- 1.82], p = 0.005); platelet count (sHR 0.98 [95% CI 0.98-0.99], p<0.001); IMV at ICU admission (sHR 1.41 [95% CI 1.16- 1.73], p<0.001); and systemic steroids (sHR 0.61 [95%CI 0.48- 0.77], p<0.001). CONCLUSIONS: Amongst critically-ill COVID-19 ventilated patients, those aged ≥70 years presented significantly higher rates of in-hospital mortality than younger patients. Increasing age, previous admission within the last 30 days, chronic heart disease, chronic renal failure, platelet count, IMV at ICU admission and systemic steroids (protective) all comprised independent factors for in-hospital mortality in elderly patients.

Evolution of the consumption trend of proton pump inhibitors in the Lleida Health Region between 2002 and 2015.

BACKGROUND: Proton pump inhibitors (PPIs) are one of the most commonly prescribed pharmacological groups. Their high prevalence and duration of use are of important health concern due to the risk they can cause to patients. Despite these risks, their use remains particularly high, especially in the elderly population. We determined the trend in the prevalence of PPI consumption in the population of the Lleida Health Region between 2002 and 2015 to explore patterns of use and associated characteristics. METHODS: An analysis of secular trends between 2002 and 2015 was performed. The database included all individuals who used PPIs in the Lleida Health Region, which had 358.070 inhabitants in 2015. PPI use was evaluated using prescription dispensing data from the public health system. All types of PPIs approved by the pharmaceutical agency were included. Trends were investigated by age and sex. RESULTS: For the whole study period, a total of 215,417 individuals accounted for 292,122 dispensations. Overall, 48% were women, and the mean age was 62 years. The dispensing prevalence of PPI use in 2015 was 18.0% overall-20.4% for women and 15.7% for men-and was 54.6% for those over 65 years. In terms of the subtypes of PPIs, 16.8% of prescriptions were for omeprazole, 0.66% were for pantoprazole, and 0.48% were for lansoprazole. The evolution of the annual PPIs dispensation prevalence showed a progressive increase from 11.3% in 2002 to 18.0% in 2015, which was attributable to an increase in the use of omeprazole (9.0% vs. 16.8%) and, to a lesser extent, esomeprazole (0.02% vs. 0.4%). CONCLUSION: An increase in the prevalence of PPI dispensation was observed over 14 years of follow-up. The prevalence of dispensation was especially high for the population older than 65 years, despite the risk of cognitive decline and falls. Comprehensive actions are required to to increase rational prescribing of PPIs, especially in high-risk populations.

Multidisciplinary virtual management of pulmonary nodules.

INTRODUCTION AND OBJECTIVES: Multidisciplinary nodule clinics provide high-quality care and favor adherence to guidelines. Virtual care has shown savings benefits along with patient satisfaction. Our aim is to describe the first year of operation of a multidisciplinary virtual lung nodule clinic, the population evaluated and issued decisions. Secondarily, among discharged patients, we aimed to analyze their follow-up prior to the existence of our consultation, evaluating its adherence to guidelines. MATERIALS AND METHODS: Observational study including all patients evaluated at the Virtual Lung Nodule Clinic (VLNC) (March 2018- March 2019). Clinical and radiological data were recorded. Recommendations, based on 2017 Fleischner Society guidelines, were categorized into follow-up, discharge or referral to lung cancer consultation. Discharged patients were classified according to adherence to guidelines of their previous management, into adequate, prolonged and non-indicated follow-up. RESULTS: A total of 365 patients (58.9% men; median age 64.0 years) were included. Sixty-four percent had smoking history and 23% had chronic obstructive pulmonary disease (COPD). Most nodules were solid (87.4%) and multiple (57.5%). The median diameter was 6.00 mm. 43.8% of patients were discharged following first VLNC evaluation. Among them, 27.5% had received appropriate follow-up, but 66.9% had received poor management. Patients with prolonged follow-up (33.1%) were older (67.0 vs 60.5 years) and had larger nodules (6.00 mm vs 5.00). Non-indicated follow-up patients (33.8%) were more non-smokers (77.8% vs 31.8%) and presented smaller nodules (4.00 vs 5.00 mm). CONCLUSIONS: During its first year of operation, the VLNC has evaluated a population with a relevant risk profile for lung cancer development, management of which should be cautious and adhere to guidelines. After the first VLNC assessment, approximately one-half of this population was discharged. It was noticeable that previous follow-up of discharged patients was found poorly adherent to guidelines, with a marked tendency to overmanagement.

Identification and validation of endogenous control miRNAs in plasma samples for normalization of qPCR data for Alzheimer's disease.

BACKGROUND: MicroRNAs (miRNAs) are noncoding RNAs that are highly relevant as disease biomarkers. Several studies that explored the role of miRNAs in Alzheimer's disease (AD) demonstrated their usefulness in clinical identification. Nevertheless, miRNAs that may act as endogenous controls (ECs) have not yet been established. The identification of ECs would contribute to the standardization of these biomarkers in AD. The objective of the study was to identify miRNAs that can be used as ECs in AD. METHODS: We evaluated 145 patients divided into two different cohorts. One was a discovery cohort of 19 women diagnosed with mild to moderate AD (Mini-Mental State Examination (MMSE) score ≥ 20) and with confirmed pathologic levels of Aß42 in CSF. The stability assessment cohort consisted of 126 individuals: 24 subjects without AD or any kind of dementia and negative for all core CSF biomarkers of AD, 25 subjects with MCI and negative for CSF biomarkers (MCI -), 22 subjects with MCI and positive for CSF biomarkers (MCI +), and 55 subjects with AD and positive for CSF biomarkers. In the discovery cohort, a profile of 384 miRNAs was determined in the plasma by TaqMan low-density array. The best EC candidates were identified by mean-centering and concordance correlation restricted normalization methods. The stability of the EC candidates was assessed using the GeNorm, BestKeeper, and NormFinder algorithms. RESULTS: Nine miRNAs (hsa-miR-324-5p, hsa-miR-22-5p, hsa-miR-103a-2-5p, hsa-miR-362-5p, hsa-miR-425-3p, hsa-miR-423-5p, hsa-let-7i-3p, hsa-miR-532-5p, and hsa-miR-1301-3p) were identified as EC candidates in the discovery cohort. The validation results indicated that hsa-miR-103a-2-5p was the best EC, followed by hsa-miR-22-5p, hsa-miR-1301-3p, and hsa-miR-425-3p, which had similar stability values in all three algorithms. CONCLUSIONS: We identified a profile of four miRNAs as potential plasma ECs to be used for normalization of miRNA expression data in studies of subjects with cognitive impairment.

Protein succination as a potential surrogate biomarker of airway obstruction. The ilervas project.

BACKGROUND: Airway obstruction (AO) is associated with hypoxemia, systemic inflammation and oxidative stress. These conditions can favor the formation of Advanced Glycation End-products (AGEs) and induce mitochondrial stress. The latter can alter metabolite intermediates in the Krebs cycle leading to the formation of the cysteine-fumarate adduct S-(2-succino) cysteine (2SC) in proteins (protein succination). Protein succination has not been described in airways diseases. RESEARCH QUESTION: To assess differences in levels of AGEs and 2SC between patients with AO and normal spirometry. STUDY DESIGN: and Methods: In this case-control study, we investigated 35 moderate to severe AO patients and 31 subjects with normal spirometry, matched for age, gender, body mass index (BMI), tobacco history, prediabetes and adherence to Mediterranean diet. Plasma 2SC and AGEs concentrations were measured by GS/MS, and AGEs in skin were determined measuring autofluorescence (SAF). Multivariate logistic regression models explored the association between AGEs in the skin, 2SC and the presence of AO. RESULTS: The population was predominantly middle-age (mean of 58.7 years-old), overweight (median of BMI 26.7 kg/m2) and male subjects (69.7%). Patients with AO showed higher values of SAF (p = 0.04) and 2SC (p = 0.047). No differences were observed for plasma AGEs. SAF and 2SC were significantly associated with the presence of AO after adjusting for age, gender, smoking history, BMI and Mediterranean diet score (p = 0.041 and p = 0.038, respectively). INTERPRETATION: Skin AGEs and 2SC are increased in patients with moderate to severe AO and independently associated with its presence. Further studies should confirm these findings and explore their potential role as a biomarker for the disease.

Circulating MicroRNA Profile Associated with Obstructive Sleep Apnea in Alzheimer's Disease.

The diagnosis of obstructive sleep apnea (OSA) in Alzheimer's disease (AD) by polysomnography (PSG) is challenging due to the required collaboration of the patients. In addition, screening questionnaires have demonstrated limited usefulness with this subpopulation. Considering this, we investigated the circulating microRNA (miRNA) profile associated with OSA in AD patients. This study included a carefully selected cohort of females with mild-moderate AD confirmed by biological evaluation (n = 29). The individuals were submitted to one-night PSG to diagnose OSA (apnea-hypopnea index ≥ 15/h) and the blood was collected in the following morning. The plasma miRNA profile was evaluated using RT-qPCR. The patients had a mean (SD) age of 75.8 (5.99) years old with a body mass index of 28.6 (3.83) kg m-2. We observed a subset of 15 miRNAs differentially expressed between OSA and non-OSA patients, of which 10 were significantly correlated with the severity of OSA. Based on this, we built a prediction model that generated an AUC (95% CI) of 0.95 (0.88-1.00) including 5 of the differentially expressed miRNAs that correlated with OSA severity: miR-26a-5p, miR-30a-3p, miR-374a-5p, miR-377-3p, and miR-545-3p. Our preliminary results suggest a plasma miRNA signature associated with the presence of OSA in AD patients. Further studies will be necessary to validate these findings.

Trends in the consumption rates of benzodiazepines and benzodiazepine-related drugs in the health region of Lleida from 2002 to 2015.

BACKGROUND: The high prevalence and long-term use of benzodiazepines (BZDs) treatment are debated topics because of the risk they can cause to the patients. Despite the current information on the risk-benefit balance of these drugs, their consumption remains particularly high. We determined the trend in the consumption prevalence of benzodiazepines (BZDs) and drugs related to BZDs (Z-drugs) in the population of the Health Region of Lleida to explore patterns of use and the associated characteristics associated between 2002 and 2015. METHODS: An analysis of secular trends was carried out between 2002 and 2015; the databased included all individuals from the Health Region of Lleida, which had 358,157 inhabitants in 2015, that consumed BZDs. The consumption of BZDs was evaluated using prescription billing data from the Public Health System. All types of BZDs and BZD analogues that had been approved by the drug agency were included. Trends by age and sex were investigated. RESULTS: Over the whole study period, a total of 161,125 individuals accounted for 338,148 dispensations. Overall, 59% were women, and the mean age was 56 years. The dispensing prevalence of BZDs use in 2015 was 14.2% overall -18.8% in women and 9.6% in men-and was 36% in those over 65 years. According to the half-life of BZDs, the prevalence of short-intermediate BZD use, intermediate-long BZD use, and Z-drugs use was 9.7, 5.5 and 0.8%, respectively. The evolution of the annual prevalence of BZD dispensing showed a progressive decline, from 15.3% in 2002 to 14.2% in 2015, which was attributed to a decrease in the consumption of intermediate-long half-life BZDs (8.0% vs. 5.5%) and Z-drugs (1.4% vs. 0.8%). CONCLUSION: The dispensing prevalence of BZDs and Z-drugs was high, although a small reduction was observed during this time period. The dispensing prevalence was especially high in the population over 65, despite the risk of cognitive decline and falls. Integral actions are required to lower the BZD prescription rate.

La comorbilidad en salud mental en los pacientes diagnosticados de enfermedad pulmonar obstructiva crónica / Comorbidity in mental health in patients diagnosed with chronic obstructive pulmonary disease

OBJETIVO: La ansiedad y la depresión juegan un papel importante en la enfermedad pulmonar obstructiva crónica aunque son escasos los estudios que han tratado de determinar su asociación con la exacerbación y todavía menos los que han tratado de cuantificar el número de exacerbaciones asociadas. El objetivo del estudio fue estudiar el riesgo de las exacerbaciones asociadas a la de ansiedad y depresión en los pacientes diagnosticados de enfermedad pulmonar obstructiva crónica. MATERIAL Y MÉTODOS: Estudio de cohortes prospectivas que analizó los factores asociados a la exacerbación en 512 enfermos durante 2 años. Las exacerbaciones se definieron como moderadas, aquellas que requirieron antibiótico/s y/o corticoides sistémicos; y graves, las que precisaron de hospitalización. Para cada paciente se registró la ansiedad y depresión (Hospital Anxiety and Depression Scale) y se cuantificaron el número de exacerbaciones durante el periodo de seguimiento. RESULTADOS: La prevalencia de ansiedad/depresión al inicio del estudio fue del 15,6%. Durante los 2 años de seguimiento la media de exacerbaciones fue de 2,21. Los pacientes que además presentaban ansiedad/depresión al inicio del estudio presentaron una media de exacerbaciones mayor, de 2,8 (p = 0,001). La ansiedad/depresión se asociaron con un mayor número de exacerbaciones moderadas-graves en el análisis ajustado (IRRa=1,48). Los otros factores de riesgo asociados a un mayor número de exacerbaciones fueron el antecedente de exacerbación grave previa (IRRa=1,50; la obesidad (IRRa=1,27); el sobrepeso (IRRa=1,23); el FEV1 ≤ 77% (IRRa=0,84); y una mayor disnea (IRRa=1,14). CONCLUSIONES: Los enfermos con ansiedad/depresión presentan un mayor número de exacerbaciones y tienen un 48% más de riesgo de padecer una exacerbación respecto a los enfermedad pulmonar obstructiva crónica sin ansiedad/depresión

OBJECTIVE: Anxiety and depression play an important role in chronic obstructive pulmonary disease, although there are a limited number of studies that have attempted to determine their relationship with exacerbations, and even less have tried to quantify the number of associated exacerbations. The aim of this study was to determine the risk of exacerbations associated with anxiety and depression in patients diagnosed with chronic obstructive pulmonary disease. MATERIAL AND METHODS: A prospective cohort study was conducted that analysed the factors associated with exacerbations in 512 patients over a 2-year period. The exacerbations that required antibiotics and/or systemic corticosteroids were defined as moderate, and those that required hospital admission, as severe. The Hospital Anxiety and Depression Scale was applied to each patient, and the number of exacerbations during follow-up were quantified. RESULTS: The prevalence of anxiety/depression at the beginning of the study was 15.6%. During the 2 years of follow-up, the mean number of exacerbations was 2.21. The patients that also had anxiety/depression at the beginning of the study had a higher mean number of exacerbations (2.8; P=.001). Anxiety/depression was associated with an increased number of moderate-severe exacerbations in the adjusted analysis (IRRa=1.48). The other risk factors associated with a higher mean number of exacerbations were, a history of a previous severe exacerbation (IRRa=1.50; obesity (IRRa=1.27); overweight (IRRa=1.23); FEV1 ≤ 77% (IRRa=0.84); and more dyspnoea (IRRa=1.14). CONCLUSIONS: Patients with anxiety/depression have a greater number of exacerbations, and have a 48% higher risk of suffering an exacerbation compared to those with chronic obstructive pulmonary disease with no anxiety/depression

Chronic obstructive pulmonary disease (COPD) in Spain and the different aspects of its social impact: a multidisciplinary opinion document.

Chronic obstructive pulmonary disease (COPD) is one of the most prevalent diseases in the World, and one of the most important causes of mortality and morbidity. In adults 40 years and older, it affects more than 10% of the population and has enormous personal, family and social burden. Tobacco smoking is its main cause, but not the only one, and there is probably a genetic predisposition that increases the risk in some patients. The paradigm of this disease is changing in Spain, with an increase of women that has occurred in recent years. Many of the physio pathological mechanisms of this condition are well known, but the psychological alterations to which it leads, the impact of COPD on relatives and caregivers, the limitation of daily life observed in these patients, and the economic and societal burden that they represent for the health system, are not so well-known. A major problem is the high under-diagnosis, mainly due to difficulties for obtaining, in a systematic way, spirometries in hospitals and health-care centers. For this reason, the Fundación de Ciencias de la Salud and the Spanish National Network Center for Research in Respiratory Diseases (CIBERES) have brought together experts in COPD, patients and their organizations, clinical psychologists, experts in health economics, nurses and journalists to obtain their opinion about COPD in Spain. They also discussed the scientific bibliometrics on COPD that is being carried out from the CIBERES and speculated on the future of this condition. The format of the meeting consisted in the discussion of a series of questions that were addressed by different speakers and discussed until a consensus conclusion was reached.

[Comorbidity in mental health in patients diagnosed with chronic obstructive pulmonary disease]. / La comorbilidad en salud mental en los pacientes diagnosticados de enfermedad pulmonar obstructiva crónica.

OBJECTIVE: Anxiety and depression play an important role in chronic obstructive pulmonary disease, although there are a limited number of studies that have attempted to determine their relationship with exacerbations, and even less have tried to quantify the number of associated exacerbations. The aim of this study was to determine the risk of exacerbations associated with anxiety and depression in patients diagnosed with chronic obstructive pulmonary disease. MATERIAL AND METHODS: A prospective cohort study was conducted that analysed the factors associated with exacerbations in 512 patients over a 2-year period. The exacerbations that required antibiotics and/or systemic corticosteroids were defined as moderate, and those that required hospital admission, as severe. The Hospital Anxiety and Depression Scale was applied to each patient, and the number of exacerbations during follow-up were quantified. RESULTS: The prevalence of anxiety/depression at the beginning of the study was 15.6%. During the 2 years of follow-up, the mean number of exacerbations was 2.21. The patients that also had anxiety/depression at the beginning of the study had a higher mean number of exacerbations (2.8; P=.001). Anxiety/depression was associated with an increased number of moderate-severe exacerbations in the adjusted analysis (IRRa=1.48). The other risk factors associated with a higher mean number of exacerbations were, a history of a previous severe exacerbation (IRRa=1.50; obesity (IRRa=1.27); overweight (IRRa=1.23); FEV1 ≤ 77% (IRRa=0.84); and more dyspnoea (IRRa=1.14). CONCLUSIONS: Patients with anxiety/depression have a greater number of exacerbations, and have a 48% higher risk of suffering an exacerbation compared to those with chronic obstructive pulmonary disease with no anxiety/depression.

The effects of superoxide dismutase-rich melon pulp concentrate on inflammation, antioxidant status and growth performance of challenged post-weaning piglets.

Piglets can often suffer impaired antioxidant status and poor immune response during post-weaning, especially when chronic inflammation takes place, leading to lower growth rates than expected. Oral administration of dietary antioxidant compounds during this period could be a feasible way to balance oxidation processes and increase health and growth performance. The aim of the trial was to study the effects of an antioxidant feed supplement (melon pulp concentrate) that contains high concentration of the antioxidant superoxide dismutase (SOD) on inflammation, antioxidant status and growth performance of lipopolysaccharide (LPS) challenged weaned piglets. In total, 48 weaned piglets were individually allocated to four experimental groups in a 2×2 factorial design for 29 days. Two different dietary treatments were adopted: (a) control (CTR), fed a basal diet, (b) treatment (MPC), fed the basal diet plus 30 g/ton of melon pulp concentrate. On days 19, 21, 23 and 25 half of the animals within CTR and MPC groups were subjected to a challenge with intramuscular injections of an increasing dosage of LPS from Escherichia coli (serotype 0.55:B5) (+) or were injected with an equal amount of PBS solution (-). Blood samples were collected at the beginning of the trial and under the challenge period for interleukin 1ß, interleukin 6, tumour necrosis factor α, haptoglobin, plasma SOD activity, total antioxidant capacity, reactive oxygen species, red blood cells and plasma resistance to haemolysis, and 8-oxo-7, 8-dihydro-2'-deoxyguanosine. Growth performance was evaluated weekly. A positive effect of melon pulp concentrate was evidenced on total antioxidant capacity, half-haemolysis time of red blood cells, average daily gain (ADG) and feed intake, while LPS challenge increased pro-inflammatory cytokines and haptoglobin serum concentrations, with a reduced feed intake and gain : feed (G : F). The obtained results show that oral SOD supplementation with melon pulp concentrate ameliorates the total antioxidant capacity and the half-haemolysis time in red blood cell of post-weaning piglets, with positive results on growing performance.

Diet supplementation with a specific melon concentrate improves oviduct antioxidant defenses and egg characteristics in laying hens.

The objectives of this study were to investigate the effects of a specific melon concentrate on oviduct antioxidant defenses and egg characteristics of laying hens.Lohmann Brown hens were assigned to 2 treatment groups (n = 16 in each). One group was supplemented with the melon concentrate (26 mg/kg of feed) during 6 wk. The other group was composed of untreated hens, which served as control. Eggs were collected, weighed (yolk, albumen, shell), and analyzed (Haugh unit and albumen pH relevant for egg freshness) at the end of the supplementation period. Antioxidant status was evaluated in the oviduct measuring antioxidant enzymes by western blotting.This study demonstrated that the melon concentrate could ameliorate egg weight, and particularly yolk contribution to egg weight and egg shell weight. An increase in endogenous antioxidant defenses in the oviduct after this melon concentrate supplementation could explain the better egg characteristics. The improvement of egg quality, due to melon concentrate, may have important economic implications for future breeding programs, particularly if these effects generalize from hens to other poultry species, or even other livestock animal species.

Risk factors for exacerbation in chronic obstructive pulmonary disease: a prospective study.

BACKGROUND: Although acute exacerbations are key events in the progression of chronic obstructive pulmonary disease (COPD), their frequency and the factors associated with acute exacerbation are not fully known. OBJECTIVE: To determine the incidence and risk factors of very frequent exacerbations in COPD (⩾3 per year). PATIENTS AND METHODS: In a cohort study to analyse acute exacerbation and associated factors in 512 primary care patients during a 2-year follow-up, variables of interest were collected for each patient. Acute exacerbation was defined as an event that required antibiotics and/or systemic steroids (moderate) or hospital admission (severe). Odds ratios (OR) were used to determine factors associated with exacerbation. RESULTS: Incidence of exacerbation was 61.7% in the first year of follow-up and 63.9% in the second year. During the first year, the factors associated with very frequent exacerbation were previous hospital admission (OR 1.69), dyspnoea (moderate [OR 2.86] and severe-very severe [OR 5.83]) and the Charlson Index (OR 1.19); during the second year, associated factors were female sex (OR 4.17), history of previous hospital admissions (OR 2.90), smoking (smoker/ex-smoker) (OR 2.00) and forced vital capacity (OR 0.98). CONCLUSIONS: Incidence of exacerbation is high in COPD patients. Previous admission for exacerbation is a strong predictor and can identify patients at risk.

Role of primary care in the follow-up of patients with obstructive sleep apnoea undergoing CPAP treatment: a randomised controlled trial.

OBJECTIVE: To evaluate whether follow-up of patients with obstructive sleep apnoea (OSA) undergoing CPAP treatment could be performed in primary care (PC) settings. DESIGN: Non-inferiority, randomised, prospective controlled study. SETTINGS: Sleep unit (SU) at the University Hospital and in 8 PC units in Lleida, Spain. PARTICIPANTS: Patients with OSA were randomised to be followed up at the SU or PC units over a 6-month period. MAIN OUTCOMES MEASURED: The primary outcome was CPAP compliance at 6 months. The secondary outcomes were Epworth Sleep Scale (ESS) score, EuroQoL, patient satisfaction, body mass index (BMI), blood pressure and cost-effectiveness. RESULTS: We included 101 patients in PC ((mean±SD) apnoea-hypopnoea index (AHI) 50.8±22.9/h, age 56.2±11 years, 74% male) and 109 in the SU (AHI 51.4±24.4/h, age 55.8±11 years, 77% male)). The CPAP compliance was (mean (95% CI) 4.94 (4.47 to 5.5) vs 5.23 (4.79 to 5.66) h, p=0.18) in PC and SU groups, respectively. In the SU group, there were greater improvements in ESS scores (mean change 1.79, 95% CI +0.05 to +3.53, p=0.04) and patient satisfaction (-1.49, 95% CI -2.22 to -0.76); there was a significant mean difference in BMI between the groups (0.57, 95% CI +0.01 to +1.13, p=0.04). In the PC setting, there was a cost saving of 60%, with similar effectiveness, as well as a decrease in systolic blood pressure (-5.32; 95% CI -10.91 to +0.28, p=0.06). CONCLUSIONS: For patients with OSA, treatment provided in a PC setting did not result in worse CPAP compliance compared with a specialist model and was shown to be a cost-effective alternative. TRIAL REGISTRATION NUMBER: Clinical Trials NCT01918449.

Gamma glutamyl transferase and oxidative stress in obstructive sleep apnea: a study in 1744 patients.

OBJECTIVE: We analyze a large population of patients to determine whether gamma glutamyl transferase (GGT) levels are increased in sleep apnea-hypopnea syndrome (OSA) and whether these levels are related to clinical characteristics or polygraphic indexes. METHODS: A cross-sectional study in a population of 1744 patients referred for OSA suspicion was conducted. The following variables were determined: glucose, cholesterol, triglycerides, aspartate aminotransferase (GOT), alanine aminotransferase (GPT), GGT, body mass index, waist-hip ratio (WHR), and overnight sleep study. RESULTS: The 483 patients with GGT ≥40 IU/l were younger and more obese, and had a pattern of more centrally distributed fat than the 1261 with GGT <40 IU/l. Patients with high levels of GGT also consumed more alcohol, had a poorer biochemical profile, and had more respiratory and oximetric alterations during sleep. GGT levels were significantly correlated with AHI, DI, and CT90. In the binary regression test, WHR, glucose, cholesterol, triglycerides, and grams of alcohol consumed per day predicted GGT levels ≥40 IU/l, while none of the polygraphic variables had predictive value. CONCLUSIONS: High GGT levels were associated with the severity of OSA. However, this relationship seems to be due to the coexistence of other associated factors, mainly central obesity, rather than to the respiratory disorders found in this disease.

Impact of obstructive sleep apnea on the 24-h metabolic hormone profile.

OBJECTIVE: Obstructive sleep apnea (OSA) has been associated with metabolic disorders. Sleep-disordered breathing could generate an altered rhythm in the expression of metabolic hormones, which could predispose to metabolic disorders. The aim of this study was to evaluate the effect of sleep apnea on diurnal variations in metabolic hormones. METHODS: Thirty-seven male, newly diagnosed, patients with OSA with an apnea-hypopnea index (AHI) > or = 20/h and 11 male controls (AHI <10/h) matched for body mass index (±3 kg/m2) were included. Six different samples were obtained from each subject during a period of 24h. Levels of the metabolic hormones ghrelin, leptin, resistin, and adiponectin were measured in plasma by immunoassay. RESULTS: Patients with OSA (AHI (mean±SD) 46±26/h) were older than the controls (42±9 vs. 33±9 years, P=0.01). Differences in metabolic hormones between groups did not reach statistical significance at any point in the evaluation. No significant differences were observed in the area under the curve for any of the hormones analysed. Likewise, we did not detect diurnal variations in metabolic hormones. CONCLUSIONS: The results of this study indicate that the day-night variations in the levels of several metabolic hormones are not influenced by the presence of sleep apnea.

Growth hormone potentiates thyroid hormone effects on post-exercise phosphocreatine recovery in skeletal muscle.

OBJECTIVE: The aim of the study was to determine the respective impact of thyroxine and growth hormone on in vivo skeletal mitochondrial function assessed via post exercise phosphocreatine recovery. DESIGN: The hind leg muscles of 32 hypophysectomized rats were investigated using (31)P nuclear magnetic resonance spectroscopy at rest and during the recovery period following a non tetanic stimulation of the sciatic nerve. Each rat was supplemented with hydrocortisone and was randomly assigned to one of the 4 groups: the group Hx was maintained in hypopituitarism., the group HxT was treated with 1 µg/100g/day of thyroxine (T4), the group HxG with 0.2 IU/kg/day of recombinant human GH (rGH) and the group HxGT by both thyroxine and rGH. Inorganic phosphate (Pi), phosphocreatine (PCr) and ATP were directly measured on the spectra, permitting the calculation of the phosphorylation potential (PP). RESULTS: At rest, the rats treated with rGH or T4 exhibited higher PCr levels than rats Hx. The recovery rates of PCr and PP were higher in rats treated with T4 than in T4-deprivated rats, suggesting improved mitochondrial function. The rats treated by both T4 and rGH showed higher PCr and PP recovery than those maintained in hypopituitarism or treated with T4 or rGH alone. CONCLUSIONS: The study demonstrates that in contrast to T4, GH given alone in hypophysectomized rats does not improve in vivo mitochondrial oxidative metabolism. Growth hormone potentiates T4 effects on oxidative metabolism.

Day-night variations in endothelial dysfunction markers and haemostatic factors in sleep apnoea.

Patients with sleep apnoea have a significant alteration in the day-night pattern of myocardial infarction and sudden cardiac death observed in the general population. The aim of this study was to investigate the influence of sleep apnoea on the diurnal variations in various haemostatic parameters (factor VII, von Willebrand factor and plasminogen activator inhibitor (PAI)-1) and markers of endothelial dysfunction (asymmetric dimethylarginine (ADMA) and soluble CD40 ligand (sCD40L)). We studied 26 male patients with obstructive sleep apnoea syndrome (OSAS; 13 patients with severe OSAS (apnoea/hypopnoea index (AHI) >30 events · h(-1)) and 13 patients with mild-to-moderate OSAS (AHI <30 events · h(-1))) and 12 controls of similar body mass index (BMI) and waist circumference. In each subject, six different samples were obtained over 24 h. Although all the markers values tended to be higher in patients with severe OSAS, differences did not reach statistical significance at any time. PAI-1 levels were significantly related to BMI (p<0.001), mean (p<0.001) and minimal (p = 0.047) nocturnal oxygenation saturation. ADMA levels were significantly related to arousal index (p = 0.046). The results of this study suggest that day-night variations in factor VII:antigen (Ag), von Willebrand factor:Ag, PAI-1, sCD40L and ADMA levels may be dependent on either the obesity index or metabolic dysfunction rather than on sleep apnoea alone.