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1.
J Clin Med ; 10(5)2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33804319

RESUMO

The nationwide claims data lake for sleep apnoea (ALASKA)-real-life data for understanding and increasing obstructive sleep apnea (OSA) quality of care study-investigated long-term continuous positive airway pressure (CPAP) termination rates, focusing on the contribution of comorbidities. The French national health insurance reimbursement system data for new CPAP users aged ≥18 years were analyzed. Innovative algorithms were used to determine the presence of specific comorbidities (hypertension, diabetes and chronic obstructive pulmonary disease (COPD)). Therapy termination was defined as cessation of CPAP reimbursements. A total of 480,000 patients were included (mean age 59.3 ± 13.6 years, 65.4% male). An amount of 50.7, 24.4 and 4.3% of patients, respectively, had hypertension, diabetes and COPD. Overall CPAP termination rates after 1, 2 and 3 years were 23.1, 37.1 and 47.7%, respectively. On multivariable analysis, age categories, female sex (1.09 (1.08-1.10) and COPD (1.12 (1.10-1.13)) and diabetes (1.18 (1.16-1.19)) were significantly associated with higher CPAP termination risk; patients with hypertension were more likely to continue using CPAP (hazard ratio 0.96 (95% confidence interval 0.95-0.97)). Therapy termination rates were highest in younger or older patients with ≥1 comorbidity. Comorbidities have an important influence on long-term CPAP continuation in patients with OSA.

2.
BMJ Case Rep ; 14(4)2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858905

RESUMO

We present the case of a baby boy, with antenatal finding of bilateral enlarged echogenic lungs, who developed severe postnatal respiratory failure. Two important differential diagnoses, which have an impact on antenatal and postnatal management, are discussed. Fetal ultrasound, MRI and postmortem MRI images are presented and findings correlated with the autopsy findings.

3.
J Clin Med ; 10(4)2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33673066

RESUMO

There are currently few data on the impact of mask resupply on longer-term adherence to positive airway pressure (PAP) therapy. This retrospective analysis investigated the effects of mask/mask cushion resupply on the adherence to PAP versus no resupply. Deidentified patient billing data for PAP supply items were merged with telemonitoring data from Cloud-connected AirSense 10/AirCurve 10 devices via AirViewTM (ResMed). Eligible patients started PAP between 1 July 2014 and 17 June 2016, had ≥360 days of PAP device data, and achieved initial U.S. Medicare adherence criteria. Patients who received a resupply of mask systems/cushions (resupply group) were propensity-score-matched with those not receiving any mask/cushion resupply (control group). A total of 100,370 patients were included. From days 91 to 360, the mean device usage was 5.6 and 4.5 h/night in the resupply and control groups, respectively (p < 0.0001). The proportion of patients with a mean device usage ≥4 h/night was significantly higher in the resupply group versus the control group (77% vs. 59%; p < 0.0001). The therapy termination rate was significantly lower in the resupply group versus the control group (14.7% vs. 31.9%; p < 0.0001); there was a trend toward lower therapy termination rates as the number of resupplies increased. The replacement of mask interface components was associated with better longer-term adherence to PAP therapy versus no resupply.

4.
J Vasc Access ; : 11297298211005267, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33769120

RESUMO

Achieving and maintaining venous access can be challenging in some premature and low birth weight infants. In this population, the supraclavicular ultrasound-guided in-plane approach to the brachiocephalic vein for central venous access has demonstrated great success with a low rate of complications. This case describes the first report of acquired chylothorax in association with this technique, in a previously extremely preterm and low birth weight infant.

5.
J Clin Sleep Med ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33666166

RESUMO

STUDY OBJECTIVES: The efficacy of portable monitor (PM) sleep testing in children is not well understood. While most studies have evaluated PM in a lab setting, the utility of PM in the home environment is relatively unknown. We sought to determine whether home PM accurately diagnoses obstructive sleep apnea (OSA) in adolescents and to assess patient satisfaction with home PM sleep testing. METHODS: We evaluated adolescents (age 12-18 years) with suspected OSA using a PM device. In addition to in-laboratory PSG, all subjects had PM testing performed twice, once in their home and once concurrent to in-laboratory PSG. PM was compared to PSG using two primary outcomes: the apnea hypopnea index (AHI) and oxygen desaturation index (ODI). All subjects were approached for interview to evaluate their experience with PM sleep testing. RESULTS: Twenty adolescents participated. Bland-Altman analysis comparing the AHI and ODI determined by home or in-laboratory PM to in-laboratory PSG, revealed mostly agreement; however, some deviations were observed when either parameter was markedly increased. While PM testing tended to underestimate the AHI, the diagnostic agreement between home PM and PSG was 80% (by the White-Westbrook method). Most preferred PM to PSG and found PM easy to very easy to set up. CONCLUSIONS: In a small cohort of adolescents, our study supports the application of home PM in the diagnosis of suspected OSA. Until studies implementing PM using larger cohorts become readily available, the findings from this preliminary study could help with adolescents receiving sleep apnea therapy more promptly. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Identifier: NCT03748771.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33565357

RESUMO

Acute respiratory distress syndrome (ARDS) is a common cause of mortality in patients with acute kidney injury (AKI). Inflammatory crosstalk from the kidney to the lung has been shown to contribute to lung injury after AKI, but anti-inflammatory therapies have not been proven beneficial in human studies. Recently, AKI was shown to alter mitochondria and related metabolic pathways in the heart, but the impact of AKI on lung metabolism has not been investigated to our knowledge. In this study, we evaluated the metabolomic profile of the lung following renal ischemia and reperfusion to identify novel pathways that may be modifiable. We randomized C57BL/6 mice to 20 minutes of bilateral renal arterial clamping or sham operation under ketamine/xylazine anesthesia. At 4 hours after reperfusion, we found a significant increase in markers of lung injury, as well as significant metabolomic changes across lung, kidney, plasma and bronchoalveolar lavage fluid (BALF) compared to shams. Comparative analyses revealed that the fatty acid oxidation pathway was the most significantly altered metabolic pathway, a finding which is consistent with mitochondrial dysfunction systemically and in the lung. These metabolomic changes correlated with the extracellular accumulation of the mitochondrial damage associated molecular patterns (mtDAMPs), mitochondrial DNA (mtDNA) and transcription factor A, mitochondria (TFAM). Finally, we found that intraperitoneal injection of renal mtDAMPs caused metabolomic changes consistent with mitochondrial dysfunction in the lung in vivo. Mitochondrial function and mtDAMPs warrant further investigation as potential therapeutic targets in preventing lung injury due to AKI.

10.
Contemp Clin Trials ; 103: 106330, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33631357

RESUMO

BACKGROUND AND AIMS: Retrospective studies have shown that angiotensin-converting-enzyme (ACE) inhibitors are associated with a reduced risk of complications and mortality in persons with novel coronavirus disease 2019 (COVID-19). Thus, we aimed to examine the efficacy of ramipril, an ACE-inhibitor, in preventing ICU admission, mechanical ventilation and/or mortality while also minimizing the risk of transmission and use of personal protective equipment (PPE). METHODS: RAMIC is a multicenter, randomized, double-blind, allocation-concealed, placebo-controlled trial comparing the efficacy of treatment with ramipril 2.5 mg orally daily compared to placebo for 14 days. The study population includes adult patients with COVID-19 who were admitted to a hospital or assessed in an emergency department or ambulatory clinic. Key exclusion criteria include ICU admission or need for mechanical ventilation at screening, use of an ACE inhibitor or angiotensin-receptor-II blocker within 7 days, glomerular filtration rate < 40 mL/min or a systolic blood pressure (BP) < 100 mmHg or diastolic BP < 65 mmHg. Patients are randomized 2:1 to receive ramipril (2.5 mg) or placebo daily. Informed consent and study visits occur virtually to minimize the risk of SARS-CoV-2 transmission and preserve PPE. The primary composite endpoint of ICU admission, invasive mechanical ventilation and death are adjudicated virtually. CONCLUSIONS: RAMIC is designed to assess the efficacy of treatment with ramipril for 14 days to decrease ICU admission, mechanical ventilator use and mortality in patients with COVID-19 and leverages virtual study visits and endpoint adjudication to mitigate risk of infection and to preserve PPE (ClinicalTrials.gov, NCT04366050).

11.
Chest ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33631141

RESUMO

BACKGROUND: Solriamfetol, a dopamine-norepinephrine reuptake inhibitor, is approved in the United States to improve wakefulness in adults with excessive daytime sleepiness (EDS) associated with OSA (37.5-150 mg/d). RESEARCH QUESTION: Does solriamfetol have differential effects on EDS based on adherence to primary OSA therapy and does solriamfetol affect primary OSA therapy use? STUDY DESIGN AND METHODS: Participants were randomized to 12 weeks of placebo or solriamfetol 37.5, 75, 150, or 300 mg/d (stratified by primary OSA therapy adherence). Coprimary end points were week 12 change from baseline in 40-min Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS) in the modified intention-to-treat population. Primary OSA therapy use (hours per night, % nights) and safety were evaluated. RESULTS: At baseline, 324 participants (70.6%) adhered to OSA therapy (positive airway pressure use ≥ 4 h/night on ≥ 70% nights, surgical intervention, or oral appliance use on ≥ 70% nights) and 135 participants (29.4%) did not adhere. Least squares (LS) mean differences from placebo in MWT sleep latency (minutes) in the 37.5-, 75-, 150-, and 300-mg/d groups among adherent participants were 4.8 (95% CI, 0.6-9.0), 8.4 (95% CI, 4.3-12.5), 10.2 (95% CI, 6.8-13.6), and 12.5 (95% CI, 9.0-15.9) and among nonadherent participants were 3.7 (95% CI, -2.0 to 9.4), 9.9 (95% CI, 4.4-15.4), 11.9 (95% CI, 7.5-16.3), and 13.5 (95% CI, 8.8-18.3). On ESS, LS mean differences from placebo in the 37.5-, 75-, 150-, and 300-mg/d groups among adherent participants were -2.4 (95% CI, -4.2 to -0.5), -1.3 (95% CI, -3.1 to 0.5), -4.2 (95% CI, -5.7 to -2.7), and -4.7 (95% CI, -6.1 to -3.2) and among nonadherent participants were -0.7 (95% CI, -3.5 to 2.1), -2.6 (95% CI, -5.4 to 0.1), -5.0 (95% CI, -7.2 to -2.9), and -4.6 (95% CI, -7.0 to -2.3). Common adverse events included headache, nausea, anxiety, decreased appetite, nasopharyngitis, and diarrhea. No clinically meaningful changes were seen in primary OSA therapy use with solriamfetol. INTERPRETATION: Solriamfetol improved EDS in OSA regardless of primary OSA therapy adherence. Primary OSA therapy use was unaffected with solriamfetol. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02348606; URL: www.clinicaltrials.gov; EU Clinical Trials Register; No.: EudraCT2014-005514-31.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33533193

RESUMO

OBJECTIVE: Recent cohort studies have identified obesity as a risk factor for poor outcomes in coronavirus disease 2019 (COVID-19). To further explore the relationship between obesity and critical illness in COVID-19, the association of BMI with baseline demographic and intensive care unit (ICU) parameters, laboratory values, and outcomes in a critically ill patient cohort was examined. METHODS: In this retrospective study, the first 277 consecutive patients admitted to Massachusetts General Hospital ICUs with laboratory-confirmed COVID-19 were examined. BMI class, initial ICU laboratory values, physiologic characteristics including gas exchange and ventilatory mechanics, and ICU interventions as clinically available were measured. Mortality, length of ICU admission, and duration of mechanical ventilation were also measured. RESULTS: There was no difference found in respiratory system compliance or oxygenation between patients with and without obesity. Patients without obesity had higher initial ferritin and D-dimer levels than patients with obesity. Standard acute respiratory distress syndrome management, including prone ventilation, was equally distributed between BMI groups. There was no difference found in outcomes between BMI groups, including 30- and 60-day mortality and duration of mechanical ventilation. CONCLUSIONS: In this cohort of critically ill patients with COVID-19, obesity was not associated with meaningful differences in respiratory physiology, inflammatory profile, or clinical outcomes.

13.
N Engl J Med ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33631066

RESUMO

BACKGROUND: Coronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials. METHODS: In this phase 3 trial, we randomly assigned patients who were hospitalized with severe Covid-19 pneumonia in a 2:1 ratio receive a single intravenous infusion of tocilizumab (at a dose of 8 mg per kilogram of body weight) or placebo. Approximately one quarter of the participants received a second dose of tocilizumab or placebo 8 to 24 hours after the first dose. The primary outcome was clinical status at day 28 on an ordinal scale ranging from 1 (discharged or ready for discharge) to 7 (death) in the modified intention-to-treat population, which included all the patients who had received at least one dose of tocilizumab or placebo. RESULTS: Of the 452 patients who underwent randomization, 438 (294 in the tocilizumab group and 144 in the placebo group) were included in the primary and secondary analyses. The median value for clinical status on the ordinal scale at day 28 was 1.0 (95% confidence interval [CI], 1.0 to 1.0) in the tocilizumab group and 2.0 (non-ICU hospitalization without supplemental oxygen) (95% CI, 1.0 to 4.0) in the placebo group (between-group difference, -1.0; 95% CI, -2.5 to 0; P = 0.31 by the van Elteren test). In the safety population, serious adverse events occurred in 103 of 295 patients (34.9%) in the tocilizumab group and in 55 of 143 patients (38.5%) in the placebo group. Mortality at day 28 was 19.7% in the tocilizumab group and 19.4% in the placebo group (weighted difference, 0.3 percentage points (95% CI, -7.6 to 8.2; nominal P = 0.94). CONCLUSIONS: In this randomized trial involving hospitalized patients with severe Covid-19 pneumonia, the use of tocilizumab did not result in significantly better clinical status or lower mortality than placebo at 28 days. (Funded by F. Hoffmann-La Roche and the Department of Health and Human Services; COVACTA ClinicalTrials.gov number, NCT04320615.).

14.
Ann Glob Health ; 87(1): 1, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33505860

RESUMO

Background: UC San Diego Health System (UCSDHS) is an academic medical center and integrated care network in the US-Mexico border area of California contiguous to the Mexican Northern Baja region. The COVID-19 pandemic deeply influenced UCSDHS activities as new public health challenges increasingly related to high population density, cross-border traffic, economic disparities, and interconnectedness between cross-border communities, which accelerated development of clinical collaborations between UCSDHS and several border community hospitals - one in the US, two in Mexico - as high volumes of severely ill patients overwhelmed hospitals. Objective: We describe the development, implementation, feasibility, and acceptance of a novel critical care support program in three community hospitals along the US-Mexico border. Methods: We created and instituted a hybrid critical care program involving: 1) in-person activities to perform needs assessments of equipment and supplies and hands-on training and education, and 2) creation of a telemedicine-based (Tele-ICU) service for direct patient management and/or consultative, education-based experiences. We collected performance metrics surrounding adherence to evidence-based practices and staff perceptions of critical care delivery. Findings: In-person intervention phase identified and filled gaps in equipment and supplies, and Tele-ICU program promoted adherence to evidence-based practices and improved staff confidence in caring for critically ill COVID-19 patients at each hospital. Conclusion: A collaborative, hybrid critical care program across academic and community centers is feasible and effective to address cross-cultural public health emergencies.


Assuntos
Centros Médicos Acadêmicos , Cuidados Críticos/métodos , Hospitais Comunitários , Comunicação Interdisciplinar , Telemedicina , Algoritmos , California , Cuidados Críticos/organização & administração , Equipamentos e Provisões Hospitalares , Medicina Baseada em Evidências , Pessoal de Saúde/educação , Humanos , Controle de Infecções/métodos , Unidades de Terapia Intensiva , Cooperação Internacional , México , Enfermagem/métodos , Autoeficácia
15.
Stem Cells Transl Med ; 10(5): 773-780, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33405397

RESUMO

Cell therapies for neonatal morbidities are progressing to early phase clinical trials. However, protocols for intravenous (IV) delivery of cell therapies to infants have not been evaluated. It has been assumed the cell dose prescribed is the dose delivered. Early in our clinical trial of human amnion epithelial cells (hAECs), we observed cells settling in the syringe and IV tubing used to deliver the suspension. The effect on dose delivery was unknown. We aimed to quantify this observation and determine an optimal protocol for IV delivery of hAECs to extremely preterm infants. A standard pediatric infusion protocol was modeled in the laboratory. A syringe pump delivered the hAEC suspension over 60 minutes via a pediatric blood transfusion set (200-µm filter and 2.2 mL IV line). The infusion protocol was varied by agitation methods, IV-line volumes (0.2-2.2 mL), albumin concentrations (2% vs 4%), and syringe orientations (horizontal vs vertical) to assess whether these variables influenced the dose delivered. The influence of flow rate (3-15 mL/h) was assessed after other variables were optimized. The standard infusion protocol delivered 17.6% ± 9% of the intended hAEC dose. Increasing albumin concentration to 4%, positioning the syringe and IV line vertically, and decreasing IV-line volume to 0.6 mL delivered 99.7% ± 13% of the intended hAEC dose. Flow rate did not affect dose delivery. Cell therapy infusion protocols must be considered. We describe the refinement of a cell infusion protocol that delivers intended cell doses and could form the basis of future neonatal cell delivery protocols.

16.
J Crit Care ; 62: 212-217, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33429114

RESUMO

PURPOSE: Sepsis remains amongst the most common causes of death worldwide. It has been described as a disease of the elderly, but contemporary data on risk factors and mortality is lacking. MATERIALS AND METHODS: Multi-center longitudinal cohort study using non-public, state of California data from January 1, 2008 to September 31, 2015. Patients with sepsis, severe sepsis, and septic shock were identified using ICD-9-CM diagnosis and procedure codes with age subgroups of 18-44, 45-64, 65-74, 75-84, and >85 years old. Descriptive statistics and a single direct logistic regression model were used to present data on incidence and mortality and to identify independent factors associated with mortality. RESULTS: Of 30,282,159 total inpatient encounters, 20,358,569 met inclusion criteria and 1,566,306 met sepsis criteria. Conditions associated with mortality included metastatic cancer, age, liver disease, residing in a care facility, and a gastrointestinal source of infection as well as fungal infection. Mortality in the >85-year-old subgroup with septic shock was 45.7%, lower than previously reported. CONCLUSION: Age remains an important sepsis risk factor, but other conditions correlated more closely with sepsis-associated death. Patients over 85 years of age suffering from septic shock may have a better chance of survival than previously thought.

17.
Sleep Med ; 77: 58-65, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33310689

RESUMO

BACKGROUND: Obstructive sleep apnoea (OSA) is an important factor in the development and progression of heart failure (HF). The prevalence of OSA is higher in patients with HF than in the general population. We sought to test the hypothesis that OSA severity was predictive of ventricular function and cardiac injury [as assessed by high-sensitivity cardiac troponin I(hs-cTnI)]. METHODS: A total of 60 patients were recruited after evaluation for sleep disturbances using the Jenkins Sleep Questionnaire (JSQ) and Epworth Sleepiness Scale (ESS). Subsequently, they underwent polysomnography thus confirming the diagnosis of OSA and were equally divided into three groups according to OSA severity grade. Following polysomnography, the next morning patients underwent venous blood sampling and echocardiography. RESULTS: We observed a statistically significant association (P = 0.009) between diastolic dysfunction grades and severity grades of OSA. All the three diastolic dysfunction variables E/A ratio, deceleration time and E/e' ratio had a significant association(P < 0.05) with severity grades of OSA. There was a marginally significant positive correlation (ρ = 0.3244, p = 0.04) between AHI events per hour and mitral E/e' ratio. There was a statistically significant association(P < 0.001) between hs-cTnI value among different severity grades of OSA. CONCLUSIONS: Here in our study, we found OSA a potential risk factor for development of myocardial injury and diastolic dysfunction. Severe grades of OSA are associated with higher grades of diastolic dysfunction and circulating levels of hs-cTnI. These data are consistent with the notion of a vicious cycle of frequent apnoea's or hypoxemia and recurrent myocardial injury, which could increase the risk of heart failure especially diastolic dysfunction in OSA.

18.
Respir Physiol Neurobiol ; 283: 103557, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33010457

RESUMO

RATIONALE: OSA has been associated with reduced exercise capacity. Endothelial dysfunction and exercise-induced pulmonary hypertension (ePH) may be mediators of this impairment. We hypothesized that OSA severity would be associated with impaired exercise performance, endothelial dysfunction, and ePH. METHODS: Subjects with untreated OSA were recruited. Subjects underwent endothelial function, and cardiopulmonary exercise testing with an echocardiogram immediately before and following exercise. RESULTS: 22 subjects were recruited with mean age 56 ± 8 years, 74 % male, BMI 29 ± 3 kg/m2, and AHI 22 ± 12 events/hr. Peak V˙O2 did not differ from normal (99.7 ± 17.3 % predicted; p = 0.93). There was no significant association between OSA severity (as AHI, ODI) and exercise capacity, endothelial function, or pulmonary artery pressure. However, ODI, marker of RV diastolic dysfunction, and BMI together explained 59.3 % of the variability of exercise performance (p < 0.001) via our exploratory analyses. CONCLUSIONS: Exercise capacity was not impaired in this OSA cohort. Further work is needed to elucidate mechanisms linking sleep apnea, obesity, endothelial dysfunction and exercise impairment.

20.
J Physiol ; 599(4): 1057-1065, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33347610

RESUMO

The clinical presentation of COVID-19 due to infection with SARS-CoV-2 is highly variable with the majority of patients having mild symptoms while others develop severe respiratory failure. The reason for this variability is unclear but is in critical need of investigation. Some COVID-19 patients have been labelled with 'happy hypoxia', in which patient complaints of dyspnoea and observable signs of respiratory distress are reported to be absent. Based on ongoing debate, we highlight key respiratory and neurological components that could underlie variation in the presentation of silent hypoxaemia and define priorities for subsequent investigation.


Assuntos
Dispneia , Humanos , Hipóxia
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