Incidencia de exacerbación grave en pacientes codiagnosticados de diabetes y enfermedad pulmonar obstructiva crónica: estudio de cohorte / Incidence of severe exacerbation in patients diagnosed with diabetes and chronic obstructive pulmonary disease: Cohort study

Objetivo: Estimar en una cohorte de pacientes diagnosticados de EPOC y diabetes la incidencia de hospitalizaciones por exacerbación grave de la EPOC y sus factores asociados. Diseño: Estudio prospectivo de cohorte. Emplazamiento: Centros de Atención Primaria de Lleida ciudad (en total 7 centros). Participantes: Se estudiaron 761 pacientes codiagnosticados de EPOC y diabetes. Los criterios de inclusión fueron pacientes de ambos sexos, igual o mayores de 40 años, residentes en el área geográfica de Lleida ciudad, con el diagnóstico de EPOC según los criterios de la guía GOLD, con espirometría reciente y una fracción FEV1/FVC <0,7; diagnosticados de DM2 según la guía de la International Diabetes Federation. Los criterios de exclusión fueron padecer alguna enfermedad física o psíquica grave. Mediciones principales: Las variables del estudio fueron: el sexo, la edad, su área básica de salud en Lleida, índice de masa corporal, perímetro de cintura, hábito tabáquico y enólico, hipertensión arterial, insuficiencia cardiaca, insuficiencia renal crónica, FEV1, FEV1/FVC, categorización GOLD, HbA1c. Se registró la vacuna antigripal y antineumocócica. La variable dependiente fue la exacerbación grave. En el análisis estadístico la asociación de la variable dependiente con las variables independientes se determinó mediante el cálculo de la hazard ratio (HR) con el intervalo de confianza del 95%. La HR se estimó de forma ajustada mediante modelos de regresión de Cox no condicional. Resultados: La incidencia de hospitalización por exacerbación grave de la EPOC fue del 9,98%; se objetivó un aumento del riesgo de exacerbación grave en pacientes diagnosticados de insuficiencia cardiaca (HR=2,27; p=0,002), y con una menor fracción de FEV1/FVC. La vacuna antigripal y antineumocócica presentaron un papel protector débil sin ser estadísticamente significativa.(AU)

Objective: To estimate the incidence of hospitalizations for severe exacerbation of chronic obstructive pulmonary disease (COPD) and its associated factors in a cohort of patients diagnosed with COPD and diabetes type 2. Design: Prospective cohort study. Site: Primary care centres of Lleida city (7 centres totally). Participants: Based on a sample of 716 patients diagnosed by COPD and diabetes. The inclusion criteria was carried out by patients of both genders, equal to or older than 40 years, ordinarily residents in the geographical area of Lleida city, with the diagnosis of COPD according to GOLD guideline, with recent spirometry and FEV1/FVC ratio <0.7; diagnosed with diabetes type 2 according to the guidelines of the International Diabetes Federation. The exclusion criteria were suffering from a serious physical or mental illness. Main measurements: The study variables were comprised by gender, age, primary care centre of Lleida, body mass index, waist circumference, smoking and enolic habit, blood pressure, heart failure, chronic renal failure, FEV1, FEV1/FVC, GOLD categorization, glycosylated haemoglobin (HbA1c). There were registered by influenza and pneumococcal vaccine. The dependent variable was severe exacerbation. In statistical analysis, the association of the dependent variable with the independent variables was determined by calculating the Hazard ratio (HR) with the 95% confidence interval. HR was estimated in an adjusted way by using unconditional Cox regression model. Results: The incidence for severe exacerbation of COPD was 9.98%; that means that an increased risk of severe exacerbation was registered in patients diagnosed with heart failure (HR=2.27; p=.002), and with lower FEV1/FVC ratio. The influenza and pneumococcal vaccines provided weak protection to prevent exacerbations, however it was not statistically significant.(AU)

[Incidence of severe exacerbation in patients diagnosed with diabetes and chronic obstructive pulmonary disease: Cohort study]. / Incidencia de exacerbación grave en pacientes codiagnosticados de diabetes y enfermedad pulmonar obstructiva crónica: estudio de cohorte.

OBJECTIVE: To estimate the incidence of hospitalizations for severe exacerbation of chronic obstructive pulmonary disease (COPD) and its associated factors in a cohort of patients diagnosed with COPD and diabetes type 2. DESIGN: Prospective cohort study. SITE: Primary care centres of Lleida city (7 centres totally). PARTICIPANTS: Based on a sample of 716 patients diagnosed by COPD and diabetes. The inclusion criteria was carried out by patients of both genders, equal to or older than 40 years, ordinarily residents in the geographical area of Lleida city, with the diagnosis of COPD according to GOLD guideline, with recent spirometry and FEV1/FVC ratio <0.7; diagnosed with diabetes type 2 according to the guidelines of the International Diabetes Federation. The exclusion criteria were suffering from a serious physical or mental illness. MAIN MEASUREMENTS: The study variables were comprised by gender, age, primary care centre of Lleida, body mass index, waist circumference, smoking and enolic habit, blood pressure, heart failure, chronic renal failure, FEV1, FEV1/FVC, GOLD categorization, glycosylated haemoglobin (HbA1c). There were registered by influenza and pneumococcal vaccine. The dependent variable was severe exacerbation. In statistical analysis, the association of the dependent variable with the independent variables was determined by calculating the Hazard ratio (HR) with the 95% confidence interval. HR was estimated in an adjusted way by using unconditional Cox regression model. RESULTS: The incidence for severe exacerbation of COPD was 9.98%; that means that an increased risk of severe exacerbation was registered in patients diagnosed with heart failure (HR=2.27; p=.002), and with lower FEV1/FVC ratio. The influenza and pneumococcal vaccines provided weak protection to prevent exacerbations, however it was not statistically significant. CONCLUSION: It documents a significant incidence of exacerbation in patients diagnosed with DM2 and COPD. Heart failure and a lower FEV1/FVC could increase the exacerbation risk.

Prognostic value of symptoms at lung cancer diagnosis: a three-year observational study.

BACKGROUND: Lung cancer is mainly diagnosed at advanced or locally advanced stages, usually when symptoms become evident. However, sometimes it may be diagnosed incidentally during routine care, while patients are still asymptomatic. Prognosis differences based on symptomatic presentation have been partially explored. Our aim was to analyze the prognostic value of the initial symptomatic state of the patients in a general lung cancer cohort. METHODS: Observational ambispective study including patients consecutively diagnosed with primary lung cancer between January 2016 and December 2018 via the lung cancer Fast Diagnostic Track (FDT). Patients were followed up until death or the end of the study in September 2019. Asymptomatic patients were compared with patients presenting symptoms. Overall survival (OS) of both groups was compared using the log-rank test. Cox regression analysis was performed to clarify the effect of the symptomatic status at diagnosis on survival. Additionally, propensity score (PS) matching analysis was performed. RESULTS: A total of 267 patients were analyzed; 83.5% were men, with a mean (SD) age at diagnosis of 68 (10.7) years. Incidental diagnosis was ascertained in 24.7% of cases. Asymptomatic patients presented more frequently stage I and II disease compared to symptomatic patients (51.5% vs. 14%), and exhibited a significantly better prognosis, with a 3-year OS of 63.6% (vs. 30.3%) and a median OS that was not reached during follow-up (vs. 10.3 months). With an adjusted multivariate Cox proportional hazard model, we obtained a HR (95% CI) of 2.63 (95% CI, 1.6-4.2; P<0.0001) associated with symptomatic presentation independently of age, sex, stage at diagnosis and ECOG scale. In addition, after performing the propensity score matching analysis, the Cox regression model continued to show a significantly worse prognosis for patients presenting with symptoms (P=0.041). CONCLUSIONS: Lung cancer patients who are asymptomatic at diagnosis exhibit a significantly better prognosis, regardless of the stage of the disease, underlining the importance of an early diagnosis.

Longitudinal Analysis of Causes of Mortality in Continuous Positive Airway Pressure-treated Patients at the Population Level.

Rationale: Randomized controlled trials do not support a role for continuous positive airway pressure (CPAP) in preventing major cardiovascular events or mortality in patients with obstructive sleep apnea (OSA). However, these trials' setting does not apply to most CPAP-treated patients. Objectives: We aimed to assess the effect of CPAP on mortality in real-world patients. Methods: We performed a population-based longitudinal observational study including all patients with OSA prescribed CPAP during 2011 in Catalonia, Spain, and non-OSA control subjects matched (1:2) by sex, 5-year age group, and region who were followed from 2011 to 2016. Results: A total of 9,317 CPAP-treated patients with OSA and 18,370 control subjects without OSA were included (median age, 67 [57-72] years; 74% male). During a median follow-up of 5.5 years, 2,301 deaths were recorded. After adjustment by a composite of diagnosed comorbidities and previous use of healthcare resources, CPAP-treated patients showed a lower risk of death than control subjects (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.61-0.74), with the association not being statistically significant in women. Cancer-related deaths were the main drivers of this association (men: HR, 0.44; 95% CI, 0.36-0.54; women: HR, 0.44; 95% CI, 0.28-0.68). No significant associations were found for cardiovascular-related deaths. CPAP-treated women had an increased risk of respiratory-related death (HR, 2.41; 95% CI, 1.37-4.23). Conclusions: CPAP-treated patients had a lower mortality rate than control subjects. This relationship was driven by cancer-related, but not cardiovascular-related, deaths. Results suggest a role for sex when prescribing CPAP, especially considering respiratory-related deaths, and foster a debate on the relationship between OSA and cardiovascular outcomes.

The Effect of Sleep Apnea on Cardiovascular Events in Different Acute Coronary Syndrome Phenotypes.

Rationale: Obstructive sleep apnea (OSA) is associated with increased cardiovascular disease (CVD) risk. Conversely, OSA has not been shown to increase recurrent cardiovascular events in patients with acute coronary syndrome (ACS). This lack of homogeneity could suggest that the deleterious effect of OSA and its contribution to CVD could depend on specific patient profiles.Objectives: To evaluate the effect of OSA on cardiovascular risk for patients with different ACS phenotypes.Methods:Post hoc analysis of the ISAACC (Continuous Positive Airway Pressure in Patients with ACS and OSA) study, including 1,701 patients admitted for ACS (NCT01335087). To evaluate the presence of OSA (apnea-hypopnea index ≥ 15 events · h-1), all patients underwent polygraphy. Patients were followed up for a minimum period of 1 year. We performed nonsupervised clustering using latent class analysis to identify subgroups of patients on the basis of 12 clinical factors associated with cardiovascular risk. The effect of OSA on recurrent cardiovascular event risk was evaluated for each phenotype identified.Measurements and Main Results: Two phenotypes were identified: patients without previous heart disease and without previous ACS ("no-previous-CVD" phenotype; 81%) and patients with previous heart disease and previous ACS ("previous-CVD" phenotype; 19%). The median (interquartile range) at follow-up was 2.67 (3.8) years. For the no-previous-CVD phenotype, the effect of OSA showed an adjusted hazard ratio (95% confidence interval) of 1.54 (1.06-2.24; P value = 0.02), whereas for the previous-CVD phenotype, the effect of OSA showed an adjusted hazard ratio of 0.69 (0.46-1.04; P value = 0.08).Conclusions: For patients with ACS and a specific phenotype, OSA is associated with an increased risk of recurrent cardiovascular events. These patients are mainly characterized by no previous heart disease and admission for a first ACS occurrence.

Effect of obstructive sleep apnoea and its treatment with continuous positive airway pressure on the prevalence of cardiovascular events in patients with acute coronary syndrome (ISAACC study): a randomised controlled trial.

BACKGROUND: Despite the improvement in the prognosis of acute coronary syndrome (ACS), substantial morbidity and mortality remain. We aimed to evaluate the effect of obstructive sleep apnoea (OSA) and its treatment with continuous positive airway pressure (CPAP) on the clinical evolution of patients with ACS. METHODS: We designed a multicentre, open-label, parallel-group, randomised controlled trial of patients with ACS at 15 hospitals in Spain. Eligible non-sleepy patients were men and women aged 18 years and older, admitted to hospital for documented symptoms of ACS. All patients underwent respiratory polygraphy during the first 24-72 h after admission. OSA patients were randomly assigned (1:1) to CPAP treatment plus usual care (CPAP group) or usual care alone (UC group) by a computerised system available 24 h a day. A group of patients with ACS but without OSA was also included as a reference group. Because of the nature of the intervention, the trial intervention could not be masked to either investigators or patients. Patients were monitored and followed for a minimum of 1 year. Patients were examined at the time of inclusion; after 1 month, 3 months, 6 months, 12 months, 18 months, 24 months, 30 months, and 36 months; and every 12 months thereafter, if applicable, during the follow-up period. The primary endpoint was the prevalence of a composite of cardiovascular events (cardiovascular death or non-fatal events [Acute myocardial infarction, non-fatal stroke, hospital admission for heart failure, and new hospitalisations for unstable angina or transient ischaemic attack]) in patients followed up for a minimum of 1 year. The primary analysis was done according to the intention-to-treat principle. This study is registered with Clinicaltrials.gov, NCT01335087 and is now closed. FINDINGS: Between April 25, 2011, and Feb 2, 2018, a total of 2834 patients with ACS had respiratory polygraphy, of whom 2551 (90·01%) were recruited. 1264 (49·55%) patients had OSA and were randomly assigned to the CPAP group (n=633) or the UC group (n=631). 1287 (50·45%) patients did not have OSA, of whom 603 (46·85%) were randomly assigned to the reference group. Patients were followed up for a median of 3·35 years (IQR 1·50-5·31). The prevalence of cardiovascular events was similar in the CPAP and UC groups (98 events [16%] vs 108 events [17%]; hazard ratio [HR] 0·89 [95% CI 0·68-1·17]; p=0·40) during follow-up. Mean time of adherence to CPAP treatment was 2·78 h/night (SD 2·73). The prevalence of cardiovascular events was similar between patients in the reference group (90 [15%] events) and those in the UC group (102 (17%) events) during follow-up (1·01 [0·76-1·35]; p=0·93). The prevalence of cardiovascular events seem not to be related to CPAP compliance or OSA severity. 464 (74%) of 629 patients in the CPAP group had 1538 serious adverse events and 406 (65%) of 626 patients in the UC group had 1764 serious adverse events. INTERPRETATION: Among non-sleepy patients with ACS, the presence of OSA was not associated with an increased prevalence of cardiovascular events and treatment with CPAP did not significantly reduce this prevalence. FUNDING: ResMed (Australia), Fondo de Investigación Sanitaria (Fondo Europeo de Desarrollo Regional), the Spanish Respiratory Society, the Catalonian Cardiology Society, Esteve-Teijin, Oxigen Salud, and ALLER.

Cardiac Troponin Values in Patients With Acute Coronary Syndrome and Sleep Apnea: A Pilot Study.

BACKGROUND: An analysis of cardiac injury markers in patients with OSA who sustain an episode of acute coronary syndrome (ACS) may contribute to a better understanding of the interactions and impact of OSA in subjects with ACS. We compared peak cardiac troponin I (cTnI) levels in patients with OSA and patients without OSA who were admitted for ACS. METHODS: Blood samples were collected every 6 hours from the time of admission until two consecutive assays showed a downward trend in the cTnI assay. The highest value obtained defined the peak cTnI value, which provides an estimate of infarct size. RESULTS: We included 89 patients with OSA and 38 patients without OSA with an apnea-hypopnea index of a median of 32 (interquartile range [IQR], 20.8-46.6/h and 4.8 [IQR, 1.6-9.6]/h, respectively. The peak cTnI value was significantly higher in patients without OSA than in patients with OSA (median, 10.7 ng/mL [IQR, 1.78-40.1 ng/mL] vs 3.79 ng/mL [IQR, 0.37-24.3 ng/mL]; P = .04). The multivariable linear regression analysis of the relationship between peak cTnI value and patient group, age, sex, and type of ACS showed that the presence or absence of OSA significantly contributed to the peak cTnI level, which was 54% lower in patients with OSA than in those without OSA. CONCLUSIONS: The results of this study suggest that OSA has a protective effect in the context of myocardial infarction and that patients with OSA may experience less severe myocardial injury. The possible role of OSA in cardioprotection should be explored in future studies.

Characterization of the CPAP-treated patient population in Catalonia.

There are different phenotypes of obstructive sleep apnoea (OSA), many of which have not been characterised. Identification of these different phenotypes is important in defining prognosis and guiding the therapeutic strategy. The aim of this study was to characterise the entire population of continuous positive airway pressure (CPAP)-treated patients in Catalonia and identify specific patient profiles using cluster analysis. A total of 72,217 CPAP-treated patients who contacted the Catalan Health System (CatSalut) during the years 2012 and 2013 were included. Six clusters were identified, classified as "Neoplastic patients" (Cluster 1, 10.4%), "Metabolic syndrome patients" (Cluster 2, 27.7%), "Asthmatic patients" (Cluster 3, 5.8%), "Musculoskeletal and joint disorder patients" (Cluster 4, 10.3%), "Patients with few comorbidities" (Cluster 5, 35.6%) and "Oldest and cardiac disease patients" (Cluster 6, 10.2%). Healthcare facility use and mortality were highest in patients from Cluster 1 and 6. Conversely, patients in Clusters 2 and 4 had low morbidity, mortality and healthcare resource use. Our findings highlight the heterogeneity of CPAP-treated patients, and suggest that OSA is associated with a different prognosis in the clusters identified. These results suggest the need for a comprehensive and individualised approach to CPAP treatment of OSA.

The Use of a Binary Composite Endpoint and Sample Size Requirement: Influence of Endpoints Overlap.

Although composite endpoints (CE) are common in clinical trials, the impact of the relationship between the components of a binary CE on the sample size requirement (SSR) has not been addressed. We performed a computational study considering 2 treatments and a CE with 2 components: the relevant endpoint (RE) and the additional endpoint (AE). We assessed the strength of the components' interrelation by the degree of relative overlap between them, which was stratified into 5 groups. Within each stratum, SSR was computed for multiple scenarios by varying the events proportion and the effect of the therapy. A lower SSR using CE was defined as the best scenario for using the CE. In 25 of 66 scenarios the degree of relative overlap determined the benefit of using CE instead of the RE. Adding an AE with greater effect than the RE leads to lower SSR using the CE regardless of the AE proportion and the relative overlap. The influence of overlapping decreases when the effect on RE increases. Adding an AE with lower effect than the RE constitutes the most uncertain situation. In summary, the interrelationship between CE components, assessed by the relative overlap, can help to define the SSR in specific situations and it should be considered for SSR computation.