Rate of severe exacerbations, healthcare resource utilisation and clinical outcomes in patients with COPD in low-income and middle-income countries: results from the EXACOS International Study.

INTRODUCTION: The EXAcerbations of Chronic obstructive lung disease (COPD) and their OutcomeS (EXACOS) International Study aimed to quantify the rate of severe exacerbations and examine healthcare resource utilisation (HCRU) and clinical outcomes in patients with COPD from low-income and middle-income countries. METHODS: EXACOS International was an observational, cross-sectional study with retrospective data collection from medical records for a period of up to 5 years. Data were collected from 12 countries: Argentina, Brazil, Chile, Colombia, Costa Rica, Dominican Republic, Guatemala, Hong Kong, Mexico, Panama, Russia and Taiwan. The study population comprised patients ≥40 years of age with COPD. Outcomes/variables included the prevalence of severe exacerbations, the annual rate of severe exacerbations and time between severe exacerbations; change in lung function over time (measured by the forced expiratory volume in 1 s (FEV1)); peripheral blood eosinophil counts (BECs) and the prevalence of comorbidities; treatment patterns; and HCRU. RESULTS: In total, 1702 patients were included in the study. The study population had a mean age of 69.7 years, with 69.4% males, and a mean body mass index of 26.4 kg/m2. The mean annual prevalence of severe exacerbations was 20.1%, and 48.4% of patients experienced ≥1 severe exacerbation during the 5-year study period. As the number of severe exacerbations increased, the interval between successive exacerbations decreased. A statistically significant decrease in mean (SD) FEV1 from baseline to post-baseline was observed in patients with ≥1 severe exacerbation (1.23 (0.51) to 1.13 (0.52) L; p=0.0000). Mean BEC was 0.198 x109 cells/L, with 64.7% of patients having a BEC ≥0.1 x109 cells/L and 21.3% having a BEC ≥0.3 x109 cells/L. The most common comorbidity was hypertension (58.3%). An increasing number of severe exacerbations per year was associated with greater HCRU. DISCUSSION: The findings presented here indicate that effective treatment strategies to prevent severe exacerbations in patients with COPD remain a significant unmet need in low-income and middle-income countries.

Analysis of Vancomycin Dosage and Plasma Levels in Critically Ill Adult Patients Requiring Extracorporeal Membrane Oxygenation (ECMO).

Introduction: Critically ill patients undergoing extracorporeal membrane oxygenation (ECMO) exhibit unique pharmacokinetics. This study aimed to assess the achievement of vancomycin therapeutic targets in these patients. Methods: This retrospective cohort study included patients on ECMO treated with vancomycin between January 2010 and December 2018. Ninety patients were analyzed based on ECMO connection modality, baseline creatinine levels, estimated glomerular filtration rate (eGFR), renal replacement therapy (RRT) requirements, and vancomycin loading dose administration. Results: Twenty-three percent of the patients achieved the therapeutic range defined by baseline levels. No significant differences in meeting the therapeutic goal were found in multivariate analysis considering ECMO cannulation modality, initial creatinine level, initial eGFR, RRT requirement, or loading dose use. All trough levels between 15 and 20 mcg/mL achieved an estimated area under the curve/minimum inhibitory concentration (AUC/MIC) between 400 and 600, almost all trough levels over 10 mcg/mL predicted an AUC/MIC >400. Discussion: Achieving therapeutic plasma levels in these patients remains challenging, potentially due to factors such as individual pharmacokinetics and pathophysiology. A trough plasma level between 12 and 20 estimated the therapeutic AUC/MIC for all models, proposing a possible lower target, maintaining exposure, and potentially avoiding adverse effects. Despite being one of the largest cohorts of vancomycin use in ECMO patients studied, its retrospective nature and single-center focus limits its broad applicability.

Severe osmotic demyelination syndrome with cortical involvement in the context of severe hyponatremia and central diabetes insipidus: an uncommon presentation of an unusual combination.

BACKGROUND: Osmotic demyelination syndrome (ODS) with cerebral cortical involvement is a rare complication of severe hyponatremia correction. Careful management of hyponatremia is crucial, particularly in patients with risk factors, such as alcohol use disorder and diabetes insipidus. CASE: A patient in his 40s with a history of alcohol use disorder and central diabetes insipidus developed ODS after a 24 mEq/L osmolar increase during the treatment of hyponatremia. The patient's condition progressed into locked-in syndrome and then improved to spastic tetraparesis after cortical basal ganglia ODS improved. DISCUSSION: The differential diagnosis of cortical demyelination includes laminar cortical necrosis, being the interpretation of Apparent Diffusion Coefficient (ADC) MRI sequence is a useful tool.This case underscores the need to investigate and improve diagnosis and treatment strategies in patients with ODS. It also emphasises the significance of careful hyponatremia correction and frequent monitoring, particularly in patients with known risk factors for ODS.

Is the time below 90% of SpO2 during sleep (T90%) a metric of good health? A longitudinal analysis of two cohorts.

BACKGROUND: Novel wireless-based technologies can easily record pulse oximetry at home. One of the main parameters that are recorded in sleep studies is the time under 90% of SpO2 (T90%) and the oxygen desaturation index 3% (ODI-3%). We assessed the association of T90% and/or ODI-3% in two different scenarios (a community-based study and a clinical setting) with all-cause mortality (primary outcome). METHODS: We included all individuals from the Sleep Heart Health Study (SHHS, community-based cohort) and Santiago Obstructive Sleep Apnea (SantOSA, clinical cohort) with complete data at baseline and follow-up. Two measures of hypoxemia (T90% and ODI-3%) were our primary exposures. The adjusted hazard ratios (HRs) per standard deviation (pSD) between T90% and incident all-cause mortality (primary outcome) were determined by adjusted Cox regression models. In the secondary analysis, to assess whether T90% varies across clinical factors, anthropometrics, abdominal obesity, metabolic rate, and SpO2, we conducted linear regression models. Incremental changes in R2 were conducted to test the hypothesis. RESULTS: A total of 4323 (56% male, median 64 years old, follow-up: 12 years, 23% events) and 1345 (77% male, median 55 years old, follow-up: 6 years, 11.6% events) patients were included in SHHS and SantOSA, respectively. Every 1 SD increase in T90% was associated with an adjusted HR of 1.18 [95% CI: 1.10-1.26] (p value < 0.001) in SHHS and HR 1.34 [95% CI: 1.04-1.71] (p value = 0.021) for all-cause mortality in SantOSA. Conversely, ODI-3% was not associated with worse outcomes. R2 explains 62% of the variability in T90%. The main contributors were baseline-mean change in SpO2, baseline SpO2, respiratory events, and age. CONCLUSION: The findings suggest that T90% may be an important marker of wellness in clinical and community-based scenarios. Although this nonspecific metric varies across the populations, ventilatory changes during sleep rather than other physiological or comorbidity variables explain their variability.

Adherence to CPAP Treatment and the Risk of Recurrent Cardiovascular Events: A Meta-Analysis.

Importance: The effect of continuous positive airway pressure (CPAP) on secondary cardiovascular disease prevention is highly debated. Objective: To assess the effect of CPAP treatment for obstructive sleep apnea (OSA) on the risk of adverse cardiovascular events in randomized clinical trials. Data Sources: PubMed (MEDLINE), EMBASE, Current Controlled Trials: metaRegister of Controlled Trials, ISRCTN Registry, European Union clinical trials database, CENTRAL (Cochrane Central Register of Controlled Trials), and ClinicalTrials.gov databases were systematically searched through June 22, 2023. Study Selection: For qualitative and individual participant data (IPD) meta-analysis, randomized clinical trials addressing the therapeutic effect of CPAP on cardiovascular outcomes and mortality in adults with cardiovascular disease and OSA were included. Data Extraction and Synthesis: Two reviewers independently screened records, evaluated potentially eligible primary studies in full text, extracted data, and cross-checked errors. IPD were requested from authors of the selected studies (SAVE [NCT00738179], ISAACC [NCT01335087], and RICCADSA [NCT00519597]). Main Outcomes and Measures: One-stage and 2-stage IPD meta-analyses were completed to estimate the effect of CPAP treatment on risk of recurrent major adverse cardiac and cerebrovascular events (MACCEs) using mixed-effect Cox regression models. Additionally, an on-treatment analysis with marginal structural Cox models using inverse probability of treatment weighting was fitted to assess the effect of good adherence to CPAP (≥4 hours per day). Results: A total of 4186 individual participants were evaluated (82.1% men; mean [SD] body mass index, 28.9 [4.5]; mean [SD] age, 61.2 [8.7] years; mean [SD] apnea-hypopnea index, 31.2 [17] events per hour; 71% with hypertension; 50.1% receiving CPAP [mean {SD} adherence, 3.1 {2.4} hours per day]; 49.9% not receiving CPAP [usual care], mean [SD] follow-up, 3.25 [1.8] years). The main outcome was defined as the first MACCE, which was similar for the CPAP and no CPAP groups (hazard ratio, 1.01 [95% CI, 0.87-1.17]). However, an on-treatment analysis by marginal structural model revealed a reduced risk of MACCEs associated with good adherence to CPAP (hazard ratio, 0.69 [95% CI, 0.52-0.92]). Conclusions and Relevance: Adherence to CPAP was associated with a reduced MACCE recurrence risk, suggesting that treatment adherence is a key factor in secondary cardiovascular prevention in patients with OSA.

Clinical Concepts for Triple Therapy Use in Patients with COPD: A Delphi Consensus.

Purpose: Role of triple therapy in chronic obstructive pulmonary disease (COPD) management is supported by growing evidence, but consensus is lacking on various aspects. We conducted a Delphi survey in respiratory experts on the effects of triple therapy on exacerbation reduction, early optimization, pneumonia risk, and mortality benefits in COPD management. Methods: The study comprised 2-round online surveys and a participant meeting with 21 respiratory experts from 10 countries. The 31-statement questionnaire was prepared using Decipher software after literature review. Responses were recorded using Likert scale ranging from 1 (disagreement) to 9 (agreement) with a consensus threshold of 75%. Results: All experts participated in both surveys and 14/21 attended participant meeting. Consensus was reached on 13/31 questions in first survey and 4/14 in second survey on: mortality benefits of triple therapy; comparable pneumonia risk between single inhaler triple therapy (SITT) and multiple inhaler triple therapy (81%); preference of SITT for patients with high eosinophil count (95%); exacerbation risk reduction and healthcare cost benefits with early initiation of SITT post exacerbation-related hospitalization (<30 days) (86%). No consensus was reached on first line SITT use after first exacerbation resulting in COPD diagnosis (62%). Conclusion: This study demonstrated that there is consensus among experts regarding many of the key concepts about appropriate clinical use and benefits of triple therapy in COPD. More evidence is required for evaluating the benefits of early optimisation of triple therapy.

Effects of changes in trunk inclination on ventilatory efficiency in ARDS patients: quasi-experimental study.

BACKGROUND: Trunk inclination from semirecumbent head-upright to supine-flat positioning reduces driving pressure and increases respiratory system compliance in patients with acute respiratory distress syndrome (ARDS). These effects are associated with an improved ventilatory ratio and reduction in the partial pressure of carbon dioxide (PaCO2). However, these physiological effects have not been completely studied, and their mechanisms have not yet been elucidated. Therefore, this study aimed to evaluate the effects of a change in trunk inclination from semirecumbent (45°) to supine-flat (10°) on physiological dead space and ventilation distribution in different lung regions. RESULTS: Twenty-two ARDS patients on pressure-controlled ventilation underwent three 60-min steps in which trunk inclination was changed from 45° (baseline) to 10° (intervention) and back to 45° (control) in the last step. Tunk inclination from a semirecumbent (45°) to a supine-flat (10°) position resulted in a higher tidal volume [371 (± 76) vs. 433 (± 84) mL (P < 0.001)] and respiratory system compliance [34 (± 10) to 41 (± 12) mL/cmH2O (P < 0.001)]. The CO2 exhaled per minute improved from 191 mL/min (± 34) to 227 mL/min (± 38) (P < 0.001). Accordingly, Bohr's dead space ratio decreased from 0.49 (± 0.07) to 0.41 (± 0.06) (p < 0.001), and PaCO2 decreased from 43 (± 5) to 36 (± 4) mmHg (p < 0.001). In addition, the impedance ratio, which divides the ventilation activity of the ventral region by the dorsal region ventilation activity in tidal images, dropped from 1.27 (0.83-1.78) to 0.86 (0.51-1.33) (p < 0.001). These results, calculated from functional EIT images, indicated further ventilation activity in the dorsal lung regions. These effects rapidly reversed once the patient was repositioned at 45°. CONCLUSIONS: A change in trunk inclination from a semirecumbent (45 degrees) to a supine-flat position (10 degrees) improved Bohr's dead space ratio and reduced PaCO2 in patients with ARDS. This effect is associated with an increase in tidal volume and respiratory system compliance, along with further favourable impedance ventilation distribution toward the dorsal lung regions. This study highlights the importance of considering trunk inclination as a modifiable determinant of physiological parameters. The angle of trunk inclination is essential information that must be reported in ARDS patients.

The U-Shaped Association between Sleep Duration, All-Cause Mortality and Cardiovascular Risk in a Hispanic/Latino Clinically Based Cohort.

Sleep is essential for life, and inappropriate sleep duration patterns may lead to chronic consequences regarding human health. Several studies have confirmed the presence of a U-shaped association between sleep duration and mortality. Moreover, many consequences related to cardiometabolic aspects have been suggested in patients with abnormal sleep durations. In this study, we analyzed the associations between sleep duration, total sleep time (TST), the risk of all-cause mortality, and 10-year cardiovascular risk in a cohort of patients at a sleep medicine center in Santiago, Chile. We conducted a prospective cohort study of patients (SantOSA). A short TST was defined as ≤6 h, a normal TST as 6 to 9 h, and a long TST as ≥9 h. Adjusted hazard ratios (aHRs) for all-cause mortality were calculated. A cross-sectional analysis between TST and 10-year cardiovascular risk (calculated using the Framingham 2008 formula) was determined using logistic regression models. A total of 1385 subjects were included in the results (78% male; median age: 53, interquartile range (IQR): 42-64 years; median BMI: 29.5, IQR: 16.7-33.1). A total of 333 subjects (24%) reported short TSTs, 938 (67.7%) reported normal TSTs, and 114 (8.3%) reported long TSTs. In the fully adjusted model, the association remained significant for short (aHR: 2.51 (1.48-4.25); p-value = 0.01) and long TSTs (aHR: 3.97 (1.53-10.29); p-value = 0.04). Finally, a U-shaped association was found between short and long TSTs, with an increase in cardiovascular risk at 10 years. Compared with normal TSTs, short (≤6 h) and long (≥9 h) TSTs were significantly associated with all-cause mortality and increased 10-year cardiovascular risk.

Clinical Application of the Multicomponent Grading System for Sleep Apnea Classification and Incident Cardiovascular Mortality.

Objective To evaluate the clinical utility of the Baveno classification in predicting incident cardiovascular mortality after five years of follow-up in a clinic-based cohort of patients with obstructive sleep apnea (OSA). Materials and Methods We evaluated the reproducibility of the Baveno classification using data from the Santiago Obstructive Sleep Apnea (SantOSA) study. The groups were labeled Baveno A (minor symptoms and comorbidities), B (severe symptoms and minor comorbidities), C (minor symptoms and severe comorbidities), and D (severe symptoms and comorbidities). Within-group comparisons were performed using analysis of variance (ANOVA) and post hoc tests. The associations between groups and incident cardiovascular mortality were determined through the Mantel-Cox and Cox proportional hazard ratios (HRs) adjusted by covariables. Results A total of 1,300 OSA patients were included (Baveno A: 27.7%; B: 28%; C: 16.8%; and D: 27.5%). The follow-up was of 5.4 years. Compared to Baveno A, the fully-adjusted risk of cardiovascular mortality with Baveno B presented an HR of 1.38 (95% confidence interval [95%CI]: 0.14-13.5; p = 0.78); with Baveno C, it was of 1.71 (95%CI: 0.18-16.2; p = 0.63); and, with Baveno D, of 1.04 (95%CI: 0.12-9.2; p = 0.98). We found no interactions involving Baveno group, sex and OSA severity. Discussion Among OSA patients, the Baveno classification can describe different subgroups. However, its utility in identifying incident cardiovascular mortality is unclear. Long-term follow-up studies and the inclusion of demographic variables in the classification could improve its ability to detect a high-risk phenotype associated with cardiovascular mortality. Conclusion The Baveno classification serves as a valuable method for categorizing varying groups of patients afflicted with OSA. Nevertheless, its precision in identifying occurrence of cardiovascular mortality is still unclear.

Undiagnosed sleep disorder breathing as a risk factor for critical COVID-19 and pulmonary consequences at the midterm follow-up.

INTRODUCTION: Patients with severe COVID-19 develops an acute respiratory distress syndrome (ARDS), requiring admission to the intensive care unit. COVID-19 also reports an increased prevalence of comorbidities, similar to patients with Sleep disorder breathing (SDB). OBJECTIVES: To evaluate the association between undiagnosed SDB and the risk of ARDS and pulmonary abnormalities in a cohort of patients' survivors of COVID-19 between 3 and 6 months after diagnosis. METHODS: Prospective cohort study of patients who developed ARDS during hospitalization due to COVID-19 compared with a control group of patients who had COVID-19 with mild to moderate symptoms. All patients were evaluated between the 12th and 24th week after SARS-CoV-2 infection. The evaluation includes persistent symptoms, lung diffusing capacity of carbon monoxide (DLCO), chest CT scan and home sleep apnea test. SDB was diagnosed by the respiratory disturbance index ≥5 ev/h. The association between SDB and ARDS, the hazards of lung impairment and the hazard ratios (HR) were analyzed. RESULTS: A total of 60 patients were included (ARDS: 34 patients, Control: 26 patients). The mean follow-up was 16 weeks (range 12-24). ARDS reported a high prevalence of SDB (79% vs. 38% in control group). A total of 35% reported DLCO impairment, and 67.6% abnormal chest CT. SDB was independently associated to ARDS, OR 6.72 (CI, 1.56-28.93), p < 0.01, and abnormal Chest CT, HR 17.2 (CI, 1.68-177.4, p = 0.01). Besides, ARDS, days in mechanical ventilation, male gender were also associated with an increased risk of abnormal chest CT. CONCLUSION: Undiagnosed SDB is prevalent and independently associated with ARDS. In addition, undiagnosed SDB increased the hazard of abnormal Chest CT in the midterm. STUDY REGISTER: ISRCTN16865246.

Clinical characteristics and predictors of hospitalization among 7,108 ambulatory patients with positive RT-PCR for SARS-CoV-2 during the acute pandemic period.

OBJECTIVE: To describe baseline characteristics of outpatients with a positive RT-PCR for SARS-CoV-2 and to define whether "red flags" (new-onset fever, dyspnea, and chest pain) can predict clinical worsening during the isolation period. METHODS: This was an epidemiological, observational, descriptive study. Between March and September of 2020, all outpatients who tested positive for SARS-CoV-2 at a tertiary medical center located in Santiago de Chile were included. Demographic variables, comorbidities, red flags, and other symptoms were compiled using follow-up surveys at specific time points. The risk of clinical worsening (hospitalization) and adjusted hazard ratios (HRs) were calculated. RESULTS: A total of 7,108 patients were included. The median age was 38 years (range, 0-101), and 52% were men. At baseline, 77% of the patients reported having characteristic symptoms of SARS-CoV-2 infection. The most prevalent onset symptoms were headache (53%), myalgia (47%), and fever (33%). According to the follow-up surveys, the incidence of symptoms decreased during the isolation period; however, 28% of the patients still presented with symptoms on day 14. The risk of hospitalization for patients with new-onset fever and dyspnea during the follow-up period was HR = 7.43 (95% CI, 3.85-14.3, p<0.01) and HR = 5.27 (95% CI, 1.52-18.30; p < 0.01 for both), respectively. New-onset chest pain showed no association with clinical worsening. CONCLUSIONS: In this sample of outpatients with a recent diagnosis of SARS-CoV-2 infection, a survey-based monitoring of symptoms was useful to identify those at risk of clinical worsening. New-onset fever and dyspnea during the isolation period were considered as red flags associated with clinical worsening and warrants prompt medical evaluation.

Telemedicine interventions for CPAP adherence in obstructive sleep apnea patients: Systematic review and meta-analysis.

Continuous positive airway pressure (CPAP) is the preferred therapy in patients with obstructive sleep apnea (OSA). However, data suggests treatment adherence is low. In recent years, telemedicine-based intervention (TM) has been evaluated to increase adherence. In this systematic review and meta-analysis of randomized controlled trials (RCTs), we evaluated the efficacy of TM on CPAP adherence in patients with OSA. Two independent reviewers explored five databases; the risk of bias (RoB) was evaluated using the Cochrane tool. Outcomes were defined as the mean difference (MD) in CPAP use per night and the proportion of patients with increased CPAP adherence of ≥4 h/night. The meta-analysis was conducted following the DerSimonian-Laird method, and the certainty of the evidence was rated according to GRADE. We included 16 RCTs including 3039 participants. The RoB was low in 12/16 studies. TM was associated with an increase in CPAP adherence of 29.2 min/night, I2 =75% (p < 0.01), and CPAP adherence ≧4 h/night, RR: 1.09 (1.02-1.17), I2 =22%. Subgroup analyses reported better results between three and 6 months, in the sleepy subgroup. Finally, based on the results obtained in this systematic review, there is favorable evidence regarding the treatment with TM in patients with OSA using CPAP. REVIEW REGISTRATION NUMBER: CRD42020165367.

A Validation Study of Four Different Cluster Analyses of OSA and the Incidence of Cardiovascular Mortality in a Hispanic Population.

BACKGROUND: Previous studies reported a strong association between sleepiness-related symptoms and comorbidities with poor cardiovascular outcomes among patients with moderate to severe OSA (msOSA). However, the validation of these associations in the Hispanic population from South America and the ability to predict incident cardiovascular disease remain unclear. RESEARCH QUESTION: In Hispanic patients with msOSA, are four different cluster analyses reproducible and able to predict incident cardiovascular mortality? STUDY DESIGN AND METHODS: Using the SantOSA cohort, we reproduced four cluster analyses (Sleep Heart Health Study [SHHS], Icelandic Sleep Apnea Cohort [ISAC], Sleep Apnea Cardiovascular Endpoints [SAVE], and The Institute de Recherche en Sante Respiratoire des Pays de la Loire [IRSR] cohorts) following a cluster analysis similar to each training dataset. The incidence of cardiovascular mortality was constructed using a Kaplan-Meier (log-rank) model, and Cox proportional hazards models were adjusted by confounders. RESULTS: Among 780 patients with msOSA in our cohort, two previous cluster analyses (SHHS and ISAC) were reproducible. The SAVE and IRSR cluster analyses were not reproducible in our sample. We identified the following subtypes for SHHS: "minimally symptomatic," "disturbed sleep," "moderate sleepiness," and "severe sleepiness." For ISAC, three different subtypes ("minimally symptomatic," "disturbed sleep," and "excessive sleepiness") were similar to the original dataset. Compared with "minimally symptomatic," we found a significant association between "excessive sleepiness" and cardiovascular mortality after 5 years of follow-up in SantOSA, hazard ratio (HR), 5.47; 95% CI, 1.74-8.29; P < .01; and HR, 3.23; 95% CI, 1.21-8.63; P = .02, using the SHHS and ISAC cluster analyses, respectively. INTERPRETATION: Among patients with msOSA, a symptom-based approach can validate different OSA patient subtypes, and those with excessive sleepiness have an increased risk of incident cardiovascular mortality in the Hispanic population from South America.

Efficacy of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) and resistant hypertension (RH): Systematic review and meta-analysis.

Approximately 70-85% of patients with resistant hypertension (RH) report obstructive sleep apnea (OSA). However, whether therapy with continuous positive airway pressure (CPAP) improves blood pressure (BP) in this population is not clear. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the efficacy of CPAP in patients with OSA and RH. Two reviewers performed the literature search, risk of bias analysis, and data extraction. The pooled data were analyzed in a meta-analysis using the DerSimonian-Laird method. We calculated the mean difference (MD) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured at 24 h and in the daytime and nighttime. We also evaluated changes in aortic stiffness and aldosterone excretion. A total of 10 RCTs and 606 participants were included. CPAP was associated with changes in 24-h SBP (-5.06 mmHg; CI, -7.98, -2.13), 24-h DBP (-4.21 mmHg; CI, -6.5, -1.93), daytime SBP (-2.34 mmHg; CI, -6.94, +2.27), daytime DBP (-2.14 mmHg; CI, -4.96, -0.67), nighttime SBP (-4.15 mmHg; CI, -7.01, -1.29), and nighttime DBP (-1.95 mmHg; CI, -3.32, -0.57). We found no benefit for aortic stiffness, but it did lead to a mild reduction in aldosterone secretion. CPAP therapy improved BP, especially nighttime BP, in this population.

Cuadro clínico del COVID-19 / Clinical presentation of COVID-19

El Coronavirus SARS-CoV-2 produce la enfermedad COVID-19, cuya manifestación más grave y potencialmente letal es la neumonía. En este artículo revisaremos las manifestaciones clínicas del COVID-19, la fisiopatología de la neumonía, el manejo intrahospitalario previo al ingreso a Unidades de Cuidados Intensivos, la embolia pulmonar que es una complicación muy frecuente de esta enfermedad y el seguimiento de los pacientes posterior al alta. Para esta publicación nos hemos basado en publicaciones médicas y en estudios que hemos hecho durante esta pandemia en nuestro Centro de Enfermedades Respiratorias. i:es

The SARS-CoV-2 Coronavirus causes the COVID-19 disease, the most severe and potentially fatal manifestation of which is pneumonia. In this article, we will review the clinical manifestations of COVID-19, the pathophysiology of pneumonia, in-hospital management prior to admission to Intensive Care Units, pulmonary embolism, which is a very frequent complication of this disease, and the follow-up of patients after hospitalization. For this publication we have relied on medical publications and studies that we have done during this pandemic at our Center for Respiratory Diseases. i:en

Risk of mortality among patients with moderate to severe obstructive sleep apnea and diabetes mellitus: results from the SantOSA cohort.

INTRODUCTION: Patients with obstructive sleep apnea (OSA) and comorbid diabetes mellitus (DM) are reported to have an increased risk of cardiovascular (CV) outcomes; however, data on CV mortality are scant. AIM: This study aimed to evaluate if patients with comorbid OSA and DM have an increased risk of CV mortality that is higher than the two diseases in isolation. METHODS: In this prospective cohort study, we included patients referred for a sleep study with and without DM at baseline. We developed four study groups as follows: group 1 (reference group), OSA (-) DM (-); group 2, OSA (-) DM (+); group 3, OSA (+) DM (-); group 4, OSA (+) DM (+). Intergroup differences were evaluated using the t test and χ2 test, and multivariate analysis was performed using logistic regression. The incidence rates of CV mortality were calculated using the Kaplan-Meier (log-rank) model, and adjusted HRs were calculated using the Cox regression model. RESULTS: A total of 1447 patients were included in the analysis-group 1: 441 participants; group 2: 141 participants; group 3: 736 participants; group 4: 151 participants. The mean follow-up was 5 years. The association between OSA + DM showed an independent risk of incident CV mortality (HR 2.37, CI 1.16-4.82, p = 0.02) and an increased prevalence of coronary heart disease (OR 3.44, CI 1.73-5.59, p < 0.01). In addition, T90% was also associated with CV mortality. CONCLUSION: The coexistence of OSA + DM was associated with an independent risk of CV mortality. In addition, T90% was also associated with CV mortality.

Hypoxemic features of obstructive sleep apnea and the risk of mortality: a cluster analysis.

INTRODUCTION: Patients with moderate to severe obstructive sleep apnea (OSA) have an increased risk of cardiovascular comorbidities and mortality. Although different subtypes of OSA have been described, data about oximetric parameters and their suitability to identify a different phenotype are scant. In this study, we evaluate the association between moderate to severe OSA and oximetric parameters included in the home sleep apnea test (HSAT) and the risks of all-cause mortality, cardiovascular mortality, and cancer mortality. METHODS: Adult patients with moderate to severe OSA from a clinical cohort in Chile were included (SantOSA study). We developed a latent class analysis (LCA) incorporating oximetric measures commonly reported on HSAT. Differences between the groups were evaluated using ANOVA and the chi-squared test. Survival curves were constructed using a Kaplan-Meier (log-rank) model, and adjusted hazard ratios of mortality were calculated using a Cox regression model following a confounder analysis of cardiovascular comorbidities. RESULTS: A total of 889 patients were included in the analysis. LCA identified three different clusters: Cluster 1, "nonhypoxemic" (n = 591); cluster 2, "moderately hypoxemic" (n = 297); and cluster 3, "severely hypoxemic" (n = 115). The mean follow-up was 4.7 years. The hypoxemic groups showed an increased risk of cardiometabolic comorbidities and an independent risk of all-cause mortality (adjusted HR 1.67 (CI 1.0-2.64) p value = 0.027). The moderately hypoxemic group had an adjusted HR of 2.92 (CI 1.00-8.58), p value = 0.05, while the severely hypoxemic group had an adjusted HR of 2.55 (CI 1.08-6.02), p value = 0.031. For cardiovascular mortality, we found an HR of 2.03 (CI 0.50-8.136), p value = 0.31, and for cancer mortality, we found an HR of 5.75 (CI 1.03-32.17), p value = 0.042. CONCLUSION: Oximetric parameters are useful for describing a different phenotype with a high risk of mortality among patients with moderate to severe OSA, beyond the apnea-hypopnea index.

Clinical characteristics and predictors of hospitalization among 7, 108 ambulatory patients with positive RT-PCR for SARS-CoV-2 during the acute pandemic period / Características clínicas e preditores de hospitalização entre 7. 108 pacientes ambulatoriais com RT-PCR positivo para SARS-CoV-2 durante o período de pandemia aguda

ABSTRACT Objective: To describe baseline characteristics of outpatients with a positive RT-PCR for SARS-CoV-2 and to define whether "red flags" (new-onset fever, dyspnea, and chest pain) can predict clinical worsening during the isolation period. Methods: This was an epidemiological, observational, descriptive study. Between March and September of 2020, all outpatients who tested positive for SARS-CoV-2 at a tertiary medical center located in Santiago de Chile were included. Demographic variables, comorbidities, red flags, and other symptoms were compiled using follow-up surveys at specific time points. The risk of clinical worsening (hospitalization) and adjusted hazard ratios (HRs) were calculated. Results: A total of 7,108 patients were included. The median age was 38 years (range, 0-101), and 52% were men. At baseline, 77% of the patients reported having characteristic symptoms of SARS-CoV-2 infection. The most prevalent onset symptoms were headache (53%), myalgia (47%), and fever (33%). According to the follow-up surveys, the incidence of symptoms decreased during the isolation period; however, 28% of the patients still presented with symptoms on day 14. The risk of hospitalization for patients with new-onset fever and dyspnea during the follow-up period was HR = 7.43 (95% CI, 3.85-14.3, p<0.01) and HR = 5.27 (95% CI, 1.52-18.30; p < 0.01 for both), respectively. New-onset chest pain showed no association with clinical worsening. Conclusions: In this sample of outpatients with a recent diagnosis of SARS-CoV-2 infection, a survey-based monitoring of symptoms was useful to identify those at risk of clinical worsening. New-onset fever and dyspnea during the isolation period were considered as red flags associated with clinical worsening and warrants prompt medical evaluation.

RESUMO Objetivo: Descrever as características basais de pacientes ambulatoriais com RT-PCR positivo para SARS-CoV-2 e definir se os sintomas de alerta para gravidade (febre, dispneia e dor torácica de início recente) podem prever piora clínica durante o período de isolamento. Métodos: Trata-se de um estudo epidemiológico, observacional e descritivo. Entre março e setembro de 2020, foram incluídos todos os pacientes ambulatoriais com teste positivo para SARS-CoV-2 em um centro médico terciário localizado em Santiago do Chile. Variáveis demográficas, comorbidades, sintomas de alerta para gravidade e outros sintomas foram compilados usando pesquisas de seguimento em intervalos específicos. Também foram calculados o risco de piora clínica (hospitalização) e as razões de risco (RR) ajustadas. Resultados: Foi incluído um total de 7.108 pacientes. A mediana de idade foi de 38 anos (variação: 0-101), e 52% eram homens. No início do estudo, 77% dos pacientes relataram sintomas característicos de infecção por SARS-CoV-2. Os sintomas recentes mais prevalentes foram cefaleia (53%), mialgia (47%) e febre (33%). De acordo com as pesquisas de seguimento, a incidência de sintomas diminuiu durante o período de isolamento; no entanto, 28% dos pacientes ainda apresentavam sintomas no dia 14. O risco de hospitalização para pacientes com febre e dispneia de início recente durante o período de seguimento foi RR = 7,43 (IC95%: 3,85-14,3; p < 0,01) e RR = 5,27 (IC95%: 1,52-18,30; p < 0,01 para ambos), respectivamente. A dor torácica de início recente não mostrou associação com a piora clínica. Conclusões: Nesta amostra de pacientes ambulatoriais com um diagnóstico recente de infecção por SARS-CoV-2, um monitoramento dos sintomas baseado em pesquisa foi útil para identificar aqueles com risco de piora clínica. Febre e dispneia de início recente durante o período de isolamento foram consideradas sintomas de alerta associados ao agravamento clínico e justificam avaliação médica imediata.

A clinic-based cluster analysis in patients with moderate-severe obstructive sleep apnea (OSA) in Chile.

RATIONALE: Patients commonly report differences in either clinical or symptomatic profiles, despite having the same severity of obstructive sleep apnea (OSA). OBJECTIVE: To identify clinical and symptomatic phenotypes and to evaluate cardiovascular mortality in each phenotype. METHODS: Data from 1370 participants (788 with moderate-severe OSA and 582 controls as a reference group) were extracted using the SantOSA database. Sixteen variables were analyzed using latent class analysis to define clinical subtypes. The association between subtypes and cardiovascular mortality was evaluated using Kaplan-Meier survival analysis and the Cox proportional hazards model. Adjusted hazard ratios (HRs) with confidence intervals (CIs) were modified by cardiovascular confounders. RESULTS: The median observation period was 5.2 years. We found four clusters: cluster #1: symptomatic men with major comorbidities (n = 252); cluster #2: symptomatic women with comorbidities (n = 154); cluster #3: asymptomatic men with comorbidities (n = 143); and cluster #4: symptomatic young men without major comorbidities (n = 239). In cluster #1, mortality was 4.76% and was independently associated with age (HR 1.12; CI 1.07-1.17), type 2 diabetes mellitus (HR 3.37; CI 1.29-8.78) and coronary heart disease (HR 3.85; CI 1.27-11.56); in cluster #2, mortality was 3.89% and was independently associated with age (HR 1.12; CI 1.06-1.19) and the oxygen desaturation index (ODI, HR 1.02; CI 1.01-1.04); and in cluster #3, mortality was 3.49% (HR 3.50; CI 1.03-11.90) and was independently associated with age (HR 1.19; CI 1.10-1.29). In cluster #4, mortality was 1.25% and showed nonsignificant associations. CONCLUSION: In patients with moderate-severe OSA, we described four phenotypes of patients according to clinical features with different risks of cardiovascular mortality. STUDY REGISTER: ISRCTN62293645.

Clinical utility of oximetric parameters to identify a high-risk phenotype of moderate-severe Obstructive Sleep Apnea (OSA).

It is unclear if oximetric parameters, such as total time of SpO2  < 90%, (T90), oxygen desaturation index-3% (ODI), minimum SpO2 , are able to describe a high-risk subtype of cardiovascular (CV) comorbidities in patients with Obstructive sleep apnea (OSA) beyond the apnea-hypopnea index. OBJECTIVE: To analyzed oximetric variables in patients with moderate-severe OSA to assess their predictive value regarding as hypertension, type 2 diabetes mellitus (T2DM), coronary heart disease (CHD) and CV mortality. METHODS: Using data from SantOSA cohort, we develop receiver operating characteristic curve and area under the curve (AUC) for each parameter, defining the proposed cutoff point in a training set. Then, in a validation set with a 5 years follow-up, we evaluate the clinical differences between groups using the proposed cutoff. We also calculated adjusted Hazard Ratios (HR) of mortality using a Cox regression model. RESULTS: About 965 patients with moderate-severe OSA (525 in training and 440 in validation group) were included. The best AUC was achieved with T90 (AUC = 0.66) and ODI (AUC = 0.61). Proposed cutoffs of T90 were hypertension: 10%, T2DM: 20%, CHD: 15%, meanwhile, proposed cutoff of ODI was ≥ 30 ev for hypertension and T2DM. Regarding CV mortality, T90 ≥ 20% was independently associated with an adjusted HR 2.44 (CI, 1.21-4.94), P-value = 0.01, meanwhile, ODI ≥ 30 ev. reported and adjusted HR 1.59 (CI, 0.75-3.39), P-value = 0.22. CONCLUSION: In patients with moderate-severe OSA, oximetric parameters, especially T90 ≥ 20% remained a predictor of mortality after adjusting for a range of demographic and disease predictors.