Non-invasive ventilation in patients with an altered level of consciousness. A clinical review and practical insights

Non-invasive ventilation has gained an increasingly pivotal role in the treatment of acute hypoxemic and/or hypercapnic respira-tory failure and offers multiple advantages over invasive mechanical ventilation. Some of these advantages include the preserva-tion of airway defense mechanisms, a reduced need for sedation, and an avoidance of complications related to endotracheal intubation.Despite its advantages, non-invasive ventilation has some contraindications that include, among them, severe encephalopathy. In this review article, the rationale, evidence, and drawbacks of the use of noninvasive ventilation in the context of hypercapnic and non-hypercapnic patients with an altered level of consciousness are analyzed

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Pharmacologic therapies for adults with acute lung injury and acute respiratory distress syndrome

BACKGROUND: Multiple pharmacologic treatments have been studied for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). OBJECTIVES: Our objective was to determine the effects of pharmacologic treatments on clinical outcomes in adults with ALI or ARDS. SEARCH STRATEGY: We searched OVID versions of CENTRAL (The Cochrane Library Issue 3, 2003), MEDLINE (1966 to week 2, January 2004), EMBASE (1980 to week 4, 2004), CINAHL (1982 to week 2, January 2004), and HEALTHSTAR (1995 to December 2003); proceedings from four conferences (1994 to 2003); and bibliographies of review articles and included studies. SELECTION CRITERIA: Randomized controlled trials of pharmacologic treatments compared to no therapy or placebo for established ALI or ARDS in adults admitted to an intensive care unit, with measurement of early mortality (primary outcome), late mortality, duration of mechanical ventilation, ventilator-free days to day 28, or adverse events. We excluded trials of nitric oxide, partial liquid ventilation, fluid and nutritional interventions, oxygen, and trials in other populations reporting outcomes in subgroups of patients with ALI or ARDS. DATA COLLECTION AND ANALYSIS: Two reviewers independently screened titles and abstracts, rated studies for inclusion, extracted data and assessed methodologic quality of included studies. Disagreements were resolved by consensus in consultation with a third reviewer. For each pharmacologic therapy, we quantitatively pooled the results of studies using random effects models where permitted by the available data. We contacted study authors when clarification of the primary outcome was required. MAIN RESULTS: Thirty three trials randomizing 3272 patients met our inclusion criteria. Pooling of results showed no effect on early mortality of prostaglandin E1 (seven trials randomizing 697 patients; relative risk [RR] 0.95, 95% confidence interval [CI] 0.77 to 1.17), N-acetylcysteine (five trials randomizing 239 patients; RR 0.89, 95% CI 0.65 to 1.21), early high-dose corticosteroids (two trials randomizing 187 patients; RR 1.12, 95% CI 0.72 to 1.74), or surfactant (nine trials randomizing 1441 patients; RR 0.93, 95% CI 0.77 to 1.12). Two interventions were beneficial in single small trials; corticosteroids given for late phase ARDS reduced hospital mortality (24 patients; RR 0.20, 95% CI 0.05 to 0.81), and pentoxifylline reduced one-month mortality (RR 0.67, 95% CI 0.47 to 0.95) in 30 patients with metastatic cancer and ARDS. Individual trials of nine additional interventions failed to show a beneficial effect on prespecified outcomes. REVIEWERS' CONCLUSIONS: Effective pharmacotherapy for ALI and ARDS is extremely limited, with insufficient evidence to support any specific intervention

Clinical practice guidelines for the use of noninvasive positive-pressure ventilation and noninvasive continuous positive airway pressure in the acute care setting

Over the past two decades, the use of noninvasive positive-pressure ventilation and noninvasive continuous positive airway pressure by mask has increased substantially for acutely ill patients. Initial case series and uncontrolled cohort studies that suggested benefit in selected patients1–13 led to many randomized controlled trials (RCTs).14–151 Both methods of ventilation have been used in the setting of acute respiratory failure to avoid endotracheal intubation in different patient populations and settings, with variable success.14–69,117–123,134–141 In addition, noninvasive positive-pressure ventilation has been used to facilitate early liberation from conventional mechanical ventilation72–82 and to prevent reintubation.70,71,83–87These guidelines were developed to answer the following questions: What evidence is available in the literature to support recommendations for the use of noninvasive positive-pressure ventilation and continuous positive airway pressure for patients who are at risk of or who have acute respiratory distress or failure, patients who have undergone surgery and patients who are being weaned from mechanical ventilation or have recently undergone extubation? In addition, how can these two modes of noninvasive ventilation be optimally applied in these settings?Consensus conference statements152,153 and guidelines154–157 exist for the use of noninvasive ventiliation (the term used throughout this paper to refer to both noninvasive positive-pressure ventilation and continuous positive airway pressure) in the acute care setting. However, since publication of the two English guidelines addressing use in the acute care setting,154,156 many new RCTs have been published. In addition, the first154 of the two previous guidelines predated the development of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group methodology,158–160 and a less rigorous methodology was used in the second.156 Accordingly, we conducted a comprehensive search and appraisal of the current literature, using the GRADE methodology to assess the quality of the research and to generate clinical recommendations

High flow nasal cannula in the immediate post-operative period: a systematic review and meta-analysis

International audienceBackground: Studies have demonstrated that high-flow nasal cannula (HFNC) prevents intubation in acute hypoxic respiratory failure when compared with conventional oxygen therapy (COT). However, the data examining routine HFNC use in the immediate postoperative period are less clear.Research Question: Is routine HFNC use superior to COT or noninvasive ventilation (NIV) use in preventing intubation in patients postoperatively?Study Design and Methods: We comprehensively searched databases (PubMed, Embase, Web of Science) to identify randomized controlled trials (RCTs) that compared the effect of HFNC use with that of COT or NIV in the immediate postoperative period on reintubation, escalation of respiratory support, hospital mortality, ICU and hospital length of stay (LOS), postoperative hypoxemia, and treatment complications. We assessed individual study risk of bias (RoB) by using the revised Cochrane RoB 2 tool and rated certainty in outcomes by using the Grading of Recommendations Assessment, Development and Evaluation framework.Results: We included 11 RCTs enrolling 2,201 patients. Ten compared HFNC with COT and one with NIV. Compared with COT use, HFNC use in the postoperative period was associated with a lower reintubation rate (relative risk [RR], 0.32; 95% CI, 0.12-0.88; absolute risk reduction [ARR], 2.9%; moderate certainty) and decreased escalation of respiratory support (RR, 0.54; 95% CI, 0.31-0.94; ARR, 5.8%; very low certainty). Post hoc subgroup analysis suggested that this effect was driven by patients who were obese and/or at high risk (subgroup differences, P = .06). We did not find differences in any of the other stated outcomes between HFNC and COT. HFNC was also no different from NIV in reintubation rate, respiratory therapy failure, or ICU LOS.Interpretation: With evidence of moderate certainty, prophylactic HFNC reduces reintubation and escalation of respiratory support compared with COT in the immediate postoperative period after cardiothoracic surgery. This effect is likely driven by patients who are at high risk and/or obese. These findings support postoperative prophylactic HFNC use in the patients who are at high risk and/or obese undergoing cardiothoracic surger