Sleep and Circadian Health of Critical Survivors: A 12-Month Follow-Up Study.

OBJECTIVES: To investigate the sleep and circadian health of critical survivors 12 months after hospital discharge and to evaluate a possible effect of the severity of the disease within this context. DESIGN: Observational, prospective study. SETTING: Single-center study. PATIENTS: Two hundred sixty patients admitted to the ICU due to severe acute respiratory syndrome coronavirus 2 infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort was composed of 260 patients (69.2% males), with a median (quartile 1-quartile 3) age of 61.5 years (52.0-67.0 yr). The median length of ICU stay was 11.0 days (6.00-21.8 d), where 56.2% of the patients required invasive mechanical ventilation (IMV). The Pittsburgh Sleep Quality Index (PSQI) revealed that 43.1% of the cohort presented poor sleep quality 12 months after hospital discharge. Actigraphy data indicated an influence of the disease severity on the fragmentation of the circadian rest-activity rhythm at the 3- and 6-month follow-ups, which was no longer significant in the long term. Still, the length of the ICU stay and the duration of IMV predicted a higher fragmentation of the rhythm at the 12-month follow-up with effect sizes (95% CI) of 0.248 (0.078-0.418) and 0.182 (0.005-0.359), respectively. Relevant associations between the PSQI and the Hospital Anxiety and Depression Scale (rho = 0.55, anxiety; rho = 0.5, depression) as well as between the fragmentation of the rhythm and the diffusing lung capacity for carbon monoxide (rho = -0.35) were observed at this time point. CONCLUSIONS: Our findings reveal a great prevalence of critical survivors presenting poor sleep quality 12 months after hospital discharge. Actigraphy data indicated the persistence of circadian alterations and a possible impact of the disease severity on the fragmentation of the circadian rest-activity rhythm, which was attenuated at the 12-month follow-up. This altogether highlights the relevance of considering the sleep and circadian health of critical survivors in the long term.

Sleep Apnea Physiological Burdens and Cardiovascular Morbidity and Mortality.

Rationale: Obstructive sleep apnea is characterized by frequent reductions in ventilation, leading to oxygen desaturations and/or arousals. Objectives: In this study, association of hypoxic burden with incident cardiovascular disease (CVD) was examined and compared with that of "ventilatory burden" and "arousal burden." Finally, we assessed the extent to which the ventilatory burden, visceral obesity, and lung function explain variations in hypoxic burden. Methods: Hypoxic, ventilatory, and arousal burdens were measured from baseline polysomnograms in the Multi-Ethnic Study of Atherosclerosis (MESA) and the Osteoporotic Fractures in Men (MrOS) studies. Ventilatory burden was defined as event-specific area under ventilation signal (mean normalized, area under the mean), and arousal burden was defined as the normalized cumulative duration of all arousals. The adjusted hazard ratios for incident CVD and mortality were calculated. Exploratory analyses quantified contributions to hypoxic burden of ventilatory burden, baseline oxygen saturation as measured by pulse oximetry, visceral obesity, and spirometry parameters. Measurements and Main Results: Hypoxic and ventilatory burdens were significantly associated with incident CVD (adjusted hazard ratio [95% confidence interval] per 1 SD increase in hypoxic burden: MESA, 1.45 [1.14, 1.84]; MrOS, 1.13 [1.02, 1.26]; ventilatory burden: MESA, 1.38 [1.11, 1.72]; MrOS, 1.12 [1.01, 1.25]), whereas arousal burden was not. Similar associations with mortality were also observed. Finally, 78% of variation in hypoxic burden was explained by ventilatory burden, whereas other factors explained only <2% of variation. Conclusions: Hypoxic and ventilatory burden predicted CVD morbidity and mortality in two population-based studies. Hypoxic burden is minimally affected by measures of adiposity and captures the risk attributable to ventilatory burden of obstructive sleep apnea rather than a tendency to desaturate.

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.

Hypoxic burden to guide CPAP treatment allocation in patients with obstructive sleep apnoea: a post hoc study of the ISAACC trial.

BACKGROUND: Hypoxic burden (HB) has emerged as a strong predictor of cardiovascular risk in obstructive sleep apnoea (OSA). We aimed to assess the potential of HB to predict the cardiovascular benefit of treating OSA with continuous positive airway pressure (CPAP). METHODS: This was a post hoc analysis of the ISAACC trial (ClinicalTrials.gov: NCT01335087) including non-sleepy patients with acute coronary syndrome (ACS) diagnosed with OSA (apnoea-hypopnoea index ≥15 events·h-1) by respiratory polygraphy. Patients were randomised to CPAP or usual care and followed for a minimum of 1 year. HB was calculated as the total area under all automatically identified desaturations divided by total sleep time. Patients were categorised as having high or low baseline HB according to the median value (73.1%min·h-1). Multivariable Cox regression models were used to assess whether the effect of CPAP on the incidence of cardiovascular outcomes was dependent on the baseline HB level. RESULTS: The population (362 patients assigned to CPAP and 365 patients assigned to usual care) was middle-aged (mean age 59.7 years), overweight/obese and mostly male (84.5%). A significant interaction was found between the treatment arm and the HB categories. In the high HB group, CPAP treatment was associated with a significant reduction in the incidence of cardiovascular events (HR 0.57, 95% CI 0.34-0.96). In the low HB group, CPAP-treated patients exhibited a trend toward a higher risk of cardiovascular outcomes than those receiving usual care (HR 1.33, 95% CI 0.79-2.25). The differential effect of the treatment depending on the baseline HB level followed a dose-response relationship. CONCLUSION: In non-sleepy ACS patients with OSA, high HB levels were associated with a long-term protective effect of CPAP on cardiovascular prognosis.

Genomic communication via circulating extracellular vesicles and long-term health consequences of COVID-19.

COVID-19 continues to affect an unprecedented number of people with the emergence of new variants posing a serious challenge to global health. There is an expansion of knowledge in understanding the pathogenesis of Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the impact of the acute disease on multiple organs. In addition, growing evidence reports that the impact of COVID-19 on different organs persists long after the recovery phase of the disease, leading to long-term consequences of COVID-19. These long-term consequences involve pulmonary as well as extra-pulmonary sequelae of the disease. Noteably, recent research has shown a potential association between COVID-19 and change in the molecular cargo of extracellular vesicles (EVs). EVs are vesicles released by cells and play an important role in cell communication by transfer of bioactive molecules between cells. Emerging evidence shows a strong link between EVs and their molecular cargo, and regulation of metabolism in health and disease. This review focuses on current knowledge about EVs and their potential role in COVID-19 pathogenesis, their current and future implications as tools for biomarker and therapeutic development and their possible effects on long-term impact of COVID-19.

Robotic-assisted bronchoscopy versus CT-guided transthoracic biopsy for diagnosis of pulmonary nodules.

BACKGROUND AND OBJECTIVE: Currently, computed tomography-guided transthoracic biopsy (CTTB) is the most accurate diagnostic approach for pulmonary nodules suspected of malignancy. Traditional bronchoscopy has shown suboptimal diagnostic sensitivity, but the emergence of robotic-assisted bronchoscopy (RAB) has the potential to improve diagnostic accuracy, maximize diagnostic yield and complete mediastinal and hilar staging in a single procedure. We aim to assess the efficacy and diagnostic performance of RAB compared to CTTB for diagnosing pulmonary nodules suspected of lung cancer. METHODS: A multicenter retrospective review of consecutive patients who underwent RAB and CTTB for evaluating pulmonary nodules from January 2019 to March 2021 at Mayo Clinic Florida and Mayo Clinic Rochester, United States. Clinical and demographic information, nodule characteristics, outcomes and complications were compared between RAB and CTTB. RESULTS: A total of 225 patients were included: 113 in the RAB group and 112 in the CTTB group. Overall diagnostic yield was 87.6% for RAB and 88.4% for CTTB. For malignant disease, RAB had a sensitivity of 82.1% and a specificity of 100%, CTTB had a sensitivity of 88.5% and a specificity of 100%. Complication rate was significantly higher for CTTB compared to RAB (17% vs. 4.4%; p = 0.002). CONCLUSION: RAB, when available, can be as accurate as CTTB for sampling pulmonary nodules with similar or reduced complications and should be considered as a means for nodule biopsy, particularly when mediastinal staging is also clinically warranted.

Cardiovascular Benefit of Continuous Positive Airway Pressure in Adults with Coronary Artery Disease and Obstructive Sleep Apnea without Excessive Sleepiness.

Rationale: Randomized controlled trials of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) have not demonstrated protection against adverse cardiovascular outcomes. Recently, observational studies revealed that OSA-related cardiovascular risk is concentrated in patients with an elevated pulse rate response to respiratory events (ΔHR). Objectives: Here, in this post hoc analysis of a prospective clinical trial, we test the hypothesis that a greater pretreatment ΔHR is associated with greater CPAP-related protection against adverse cardiovascular outcomes. Methods: ΔHR was measured from baseline polysomnography of the RICCADSA (Randomized Intervention with CPAP in CAD and OSA) randomized controlled trial (patients with coronary artery disease [CAD] and OSA [apnea-hypopnea index ⩾ 15 events/h] with Epworth Sleepiness Scale score < 10; nCPAP:ncontrol = 113:113; male, 85%; age, 66 ± 8 [mean ± SD] yr). The primary outcome was a composite of repeat revascularization, myocardial infarction, stroke, and cardiovascular mortality. Multivariable Cox regression assessed whether the effect of CPAP was moderated by ΔHR (treatment-by-ΔHR interaction). Measurements and Main Results: The CPAP-related reduction in risk increased progressively with increasing pretreatment ΔHR (interaction hazard ratio [95% confidence interval], 0.49 [0.27 to 0.90] per SD increase in ΔHR; P < 0.05). This means that in patients with a ΔHR of 1 SD above the mean (i.e., 10 beats/min), CPAP was estimated to reduce cardiovascular risk by 59% (6% to 82%) (P < 0.05), but no significant risk reduction was estimated in patients with a mean ΔHR (6 beats/min; CPAP risk reduction, 16% [-53% to 54%]; P = 0.6). Conclusions: The protective effect of CPAP in patients with CAD and OSA without excessive sleepiness was modified by the ΔHR. Specifically, patients with higher ΔHR exhibit greater cardiovascular benefit from CPAP therapy.

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.

Sleep and Circadian Health of Critical COVID-19 Survivors 3 Months After Hospital Discharge.

OBJECTIVES: To evaluate the sleep and circadian rest-activity pattern of critical COVID-19 survivors 3 months after hospital discharge. DESIGN: Observational, prospective study. SETTING: Single-center study. PATIENTS: One hundred seventy-two consecutive COVID-19 survivors admitted to the ICU with acute respiratory distress syndrome. INTERVENTIONS: Seven days of actigraphy for sleep and circadian rest-activity pattern assessment; validated questionnaires; respiratory tests at the 3-month follow-up. MEASUREMENTS AND MAIN RESULTS: The cohort included 172 patients, mostly males (67.4%) with a median (25th-75th percentile) age of 61.0 years (52.8-67.0 yr). The median number of days at the ICU was 11.0 (6.00-24.0), and 51.7% of the patients received invasive mechanical ventilation (IMV). According to the Pittsburgh Sleep Quality Index (PSQI), 60.5% presented poor sleep quality 3 months after hospital discharge, which was further confirmed by actigraphy. Female sex was associated with an increased score in the PSQI (p < 0.05) and IMV during ICU stay was able to predict a higher fragmentation of the rest-activity rhythm at the 3-month follow-up (p < 0.001). Furthermore, compromised mental health measured by the Hospital Anxiety and Depression Scale was associated with poor sleep quality (p < 0.001). CONCLUSIONS: Our findings highlight the importance of considering sleep and circadian health after hospital discharge. Within this context, IMV during the ICU stay could aid in predicting an increased fragmentation of the rest-activity rhythm at the 3-month follow-up. Furthermore, compromised mental health could be a marker for sleep disruption at the post-COVID period.

Impact of time to intubation on mortality and pulmonary sequelae in critically ill patients with COVID-19: a prospective cohort study.

QUESTION: We evaluated whether the time between first respiratory support and intubation of patients receiving invasive mechanical ventilation (IMV) due to COVID-19 was associated with mortality or pulmonary sequelae. MATERIALS AND METHODS: Prospective cohort of critical COVID-19 patients on IMV. Patients were classified as early intubation if they were intubated within the first 48 h from the first respiratory support or delayed intubation if they were intubated later. Surviving patients were evaluated after hospital discharge. RESULTS: We included 205 patients (140 with early IMV and 65 with delayed IMV). The median [p25;p75] age was 63 [56.0; 70.0] years, and 74.1% were male. The survival analysis showed a significant increase in the risk of mortality in the delayed group with an adjusted hazard ratio (HR) of 2.45 (95% CI 1.29-4.65). The continuous predictor time to IMV showed a nonlinear association with the risk of in-hospital mortality. A multivariate mortality model showed that delay of IMV was a factor associated with mortality (HR of 2.40; 95% CI 1.42-4.1). During follow-up, patients in the delayed group showed a worse DLCO (mean difference of - 10.77 (95% CI - 18.40 to - 3.15), with a greater number of affected lobes (+ 1.51 [95% CI 0.89-2.13]) and a greater TSS (+ 4.35 [95% CI 2.41-6.27]) in the chest CT scan. CONCLUSIONS: Among critically ill patients with COVID-19 who required IMV, the delay in intubation from the first respiratory support was associated with an increase in hospital mortality and worse pulmonary sequelae during follow-up.

Atomoxetine and fesoterodine combination improves obstructive sleep apnoea severity in patients with milder upper airway collapsibility.

BACKGROUND AND OBJECTIVE: The combination of the noradrenergic atomoxetine plus the anti-muscarinic oxybutynin acutely increased genioglossus activity and reduced obstructive sleep apnoea (OSA) severity. However, oxybutynin has shorter half-life than atomoxetine and side effects that might discourage long-term usage. Accordingly, we aimed to test the combination of atomoxetine and fesoterodine (Ato-Feso), a newer anti-muscarinic with extended release formulation, on OSA severity and endotypes. METHODS: Twelve subjects with OSA underwent a randomized, double-blind, crossover trial comparing one night of atomoxetine plus fesoterodine (80-4 mg) to placebo. Parameters of OSA severity (e.g., apnoea-hypopnoea index [AHI], nadir oxygen desaturation and hypoxic burden) were calculated from two clinical, in-lab polysomnographic studies. OSA endotypes (including collapsibility per VMIN and arousal threshold) were derived from validated algorithms. RESULTS: Compared to placebo, Ato-Feso did not reduce the AHI (34.2 ± 19.1 vs. 30.1 ± 28.2 events/h, p = 0.493), but reduced the apnoea index (12.9 [28.8] vs. 1.8 [9.1] events/h, median [interquartile range], p = 0.027) and increased nadir desaturation (76.8 [8.0] vs. 82.2 [8.8] %, p = 0.003); a non-significant trend for improved hypoxic burden was observed (52.4 [50.5] vs. 29.7 [78.9] %min/h, p = 0.093). Ato-Feso lowered collapsibility (raised VMIN ; 43.7 [29.8-55.7] vs. 56.8 [43.8-69.8] %VEUPNOEA , mean [CI], p = 0.002), but reduced the arousal threshold (129.3 [120.1-138.6] vs. 116.7 [107.5-126] %VEUPNOEA , p = 0.038). In post hoc analysis, 6/6 patients with milder collapsibility (VMIN > 43%) exhibited OSA resolution (drop in AHI > 50% and residual AHI < 10 events/h) and improved hypoxaemia. CONCLUSION: While inefficacious in unselected patients, Ato-Feso administered for one night suppressed OSA in patients with milder collapsibility. Ato-Feso may hold some promise as an alternative OSA treatment in certain subgroups of individuals.

[Sexual, physical, mental and sleep sequelae four months after SARS-CoV-2 disease]. / Evaluación de la salud sexual, mental y sueño en hombres chilenos posterior a infección por SARS-CoV-2.

BACKGROUND: Long term sequelae can be observed after SARS-CoV2. AIM: To describe the sexual, physical, mental and sleep sequelae four months after SARS-CoV2 diagnosis. PATIENTS AND METHODS: Patients recovering from SARS-CoV2 with different degrees of disease severity were consecutively included and separated in two study groups, namely Group 1 including patients that had an acute respiratory distress syndrome (ARDS) and Group 2 including those with mild or moderate COVID-19. Handgrip strength, respiratory polygraphy (RP), Quality of life using the SF-12 questionnaire, and the international index of erectile (IIEF-5) function were assessed. RESULTS: Twenty patients who had ARDS, and 10 without ARDS were included. Erectile dysfunction was observed in 77 and 10% of patients with and without ARDS, respectively (p < 0.01). The figures for sleep obstructive apnea were 82 and 40% respectively (p = 0.02) and for the physical domain SF-12 score were 39.2 and 47.9 points respectively (p = 0.01). No differences in muscle strength were observed. After a multivariable analysis, previous ARDS due to COVID-19 was independently associated with erectile dysfunction, with an odds ratio of 30.6 (95% confidence intervals, 3.08300.3, p = 0.003). CONCLUSIONS: Among men with ARDS due to COVID-19, the prevalence of erectile dysfunction was high and independently associated with a severe disease four months after discharge.

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.

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.

[Vitamin D levels in patients with inflammatory bowel disease]. / Hipovitaminosis D en población portadora de enfermedad inflamatoria intestinal del Sur de Chile.

BACKGROUND: Inflammatory Bowell Diseases (IBD), either ulcerative colitis (UC) or Chron's disease (CD) are commonly associated with intestinal malabsorption, and insufficient levels 1-25 hydroxycholecalciferol (vitamin D). These insufficient levels could be linked with an increased risk of clinical disease activity. AIM: To report vitamin D levels in patients with IBD living in Southern Chile and their possible association with clinical disease activity. MATERIAL AND METHODS: A prospective, observational study in outpatients with IBD living in Los Angeles, Chile. Demographic data and clinical activity using clinical scores were recorded. Vitamin D levels and fecal calprotectin were measured. RESULTS: We studied 44 patients, 32 (73%) with UC and 12 (27%) with CD. The median age at diagnosis was 33 years old. Forty-one (93%) had mild-inactive disease and 3 (7%) a moderate disease. Mean vitamin D levels were 15.2 ± 7.1 ng/ml. Twenty five percent of patients had sufficient levels (> 20 ng/ml), 35% insufficient levels and 40% poor levels. No association between these levels and disease activity was found. CONCLUSIONS: These patients with IBD had a high frequency of hypovitaminosis D.

Endoscopic Lung Volume Reduction in Relation to Body Mass Index in Patients with Severe Heterogeneous Emphysema.

BACKGROUND: In chronic obstructive pulmonary disease (COPD), body mass index (BMI) is significantly lower in the emphysema-dominant type. Endoscopic lung volume reduction (ELVR) is an innovative way of treating severe emphysema. However, the specific associations of low BMI values and outcomes of ELVR is not well-studied. OBJECTIVES: We evaluated associations between initial BMI and changes in major outcomes after endobronchial valve (EBV) placement in patients with heterogeneous severe emphysema. METHODS: In a retrospective cohort study, patients were divided into 2 groups based on their baseline BMI (higher BMI ≥21 kg/m2 [n = 18] and lower BMI <21 kg/m2 [n = 63]). Demographics, procedure data, pulmonary function test and 6-min-walk test (6MWT), dyspnea score (according to the modified Medical Research Council [mMRC] scale), BODE (BMI, airflow obstruction, dyspnea, exercise capacity) index, and complications were recorded. After 6 months, changes in variables (dWeight and dBMI) were recorded. RESULTS: Comparing the 2 groups, we found the following: a dWeight of -2.34 kg and +3.39 kg (p value <0.01) and a dBMI of -0.74 and +1.99 kg/m2, in the higher BMI and lower BMI group, respectively (p value <0.01). Changes in forced expiratory volume <1 s (FEV1), 6MWT, mMRC score, and BODE index were not statistically significant. The most common complication was pneumothorax. The lower BMI group experienced more complications than the higher BMI group (40 vs. 24%). CONCLUSION: Baseline BMI is relevant when selecting candidates for ELVR. Our results show that the COPD patients with a lower BMI gained a significant amount of weight, thus increasing their BMI after the procedure. The rate of complications was higher in the lower BMI group. These findings should alert physicians and encourage nutritional assessment in this population.

Efficacy of the Spiration Valve System in Patients with Severe Heterogeneous Emphysema: A Systematic Review and Meta-Analysis.

BACKGROUND: Spiration Valve System (SVS) is an alternative for patients with severe heterogeneous emphysema; however, data about efficacy from randomized controlled trials (RCT) are unclear. OBJECTIVES: To explore both efficacy and safety of SVS in patients with severe emphysema and hyperinflation. METHODS: We included PubMed, EMBASE, Coch-rane database. All searches were performed until August 2019. Only RCTs were included for analysis. Risk of bias was assessed using Cochrane risk of bias tool. A meta-analysis evaluated change in forced expiratory volume in 1 s (FEV1), 6-min walking test (6MWT), residual volume, modified medical research council (mMRC) and Saint George respiratory questionnaire (SGRQ), all-cause mortality, risk of pneumothorax, and risk of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Quality of the evidence was rated using GRADE approach. RESULTS: Four RCTs including 629 subjects were included. SVS showed an overall change of 0.03 L (-0.07 to 0.13, I2 = 90%) in the in FEV1 (L) and a 2.03% (-2.50 to 6.57, I2 = 96%) in the predicted FEV1 (%) compared to baseline; however, studies without collateral ventilation (CV) showed an improvement of 0.12 L (95% CI 0.09-0.015, I2 = 0%), This subgroup also reported better results in SGRQ -12.27 points (95% CI -15.84 to -8.70, I2 = 0%) and mMRC -0.54 (95% CI -0.74 to -0.33, I2 = 0%). We found no benefit in 6MWT mean difference = 4.56 m (95% CI -21.88 to 31.00, I2 = 73%). Relative risk of mortality was 2.54 (95% CI 0.81-7.96, I2 = 0%), for pneumothorax 3.3 (95% CI 0.61-18.12, I2 = 0%) and AECOPD 1.68 (95% CI 1.04-2.70, I2 = 0%). CONCLUSION: In patients with severe heterogeneous emphysema and hyperinflation without CV, SVS is an alternative that showed an improvement in pulmonary function, quality of life, and dyspnea score with an acceptable risk profile.

Chronic intermittent hypoxia in obstructive sleep apnea: a narrative review from pathophysiological pathways to a precision clinical approach.

Obstructive sleep apnea syndrome (OSAS) is a prevalent condition caused by dynamic upper airway collapse during sleep. The pathological impact and consequences are due to chronic intermittent hypoxia (CIH). Hypoxia increases the expression of several inflammatory stress markers and endothelial dysfunction. Recent studies suggest that patients with a similar AHI but with severe nocturnal hypoxia using oximetric parameters, such as the lowest saturation of oxygen during the night (min SaO2), percentage of total sleep time with oxygen saturation < 90% (T90) or the oxygen desaturation index (ODI-3%), commonly reported during the sleep study, are indicative of the increased expression of inflammatory markers due to severe nocturnal hypoxia and CIH during the night compared to subjects with moderate-severe OSAS without severe nocturnal hypoxia. The aim of this review is to describe physiological pathways involved in OSAS and their clinical consequences, focused in CIH and oximetric parameters showed in sleep study and their potential utility as inflammatory markers.

[How to interpret systematic reviews with multiple comparisons or network meta-analysis]. / Como interpretar una revisión sistemática con comparaciones múltiples o network metaanálisis.

Systematic reviews evaluating multiple interventions can be useful in different clinical situations. However, some concerns arise when more than two interventions are compared and there is a paucity of good quality randomized clinical trials. A novel statistical method based on indirect comparisons, called network meta-analysis (NMA), can be a useful approach to find a clinical answer when multiple interventions are evaluated for the same outcome or comparator. The aim of this review is to describe the main characteristics and provide a user guide for a critical analysis of NMA focusing on its three main domains, namely homogeneity, transitivity and consistency.

[Association between high vitamin B12 levels and one year mortality in older people admitted to the hospital]. / Asociación entre niveles de vitamina B-12 y mortalidad en pacientes hospitalizados adultos mayores.

BACKGROUND: Supplementation of vitamin B12 in older adults is a common practice to avoid vitamin B12 insufficiency. However, there is a paucity of information about the effects of cobalamin excess. AIM: To asses any potential effects of high levels vitamin B12 on mortality on adults aged ≥ 65 years admitted to an internal medicine service. MATERIAL AND METHODS: We Prospectively studied patients admitted to an internal medicine service of an academic hospital from September 2017 to September 2018, who were able to give their consent and answer questionnaires. We tabulated age, gender, medical history, comorbidity index (Charlson), frailty score (Fried scale), admission diagnosis and blood tests performed within 48 hours of admission. The primary outcome was death by any cause in less of 30 days or after one of year follow up, determined according to death certificates. RESULTS: We included 93 patients aged 65 to 94 years (53% males). Fifteen patients died during the year of follow up (five within 30 days of admission). Those who died had higher cobalamin levels than survivors (1080.07 ± 788.09 and 656.68 ± 497.33 pg/mL respectively, p = 0.02). Patients who died had also a significantly lower corrected serum calcium, sodium (p = 0.04) and a medical history of chronic liver disease (p = 0.03). In the multivariable analysis, only vitamin B12 preserved the association with mortality (p = 0.009). CONCLUSIONS: There was a significant association between high levels of cobalamin and all-cause mortality in this group of patients aged ≥ 65 years-old.