-
Mechanical ventilation in aneurysmal subarachnoid hemorrhage: systematic review and recommendations.Critical Care (London, England) Sep 2020Mechanical ventilation (MV) has a complex interplay with the pathophysiology of aneurysmal subarachnoid hemorrhage (aSAH). We aim to provide a review of the physiology...
OBJECTIVE
Mechanical ventilation (MV) has a complex interplay with the pathophysiology of aneurysmal subarachnoid hemorrhage (aSAH). We aim to provide a review of the physiology of MV in patients with aSAH, give recommendations based on a systematic review of the literature, and highlight areas that still need investigation.
DATA SOURCES
PubMed was queried for publications with the Medical Subject Headings (MeSH) terms "mechanical ventilation" and "aneurysmal subarachnoid hemorrhage" published between January 1, 1990, and March 1, 2020. Bibliographies of returned articles were reviewed for additional publications of interest.
STUDY SELECTION
Study inclusion criteria included English language manuscripts with the study population being aSAH patients and the exposure being MV. Eligible studies included randomized controlled trials, observational trials, retrospective trials, case-control studies, case reports, or physiologic studies. Topics and articles excluded included review articles, pediatric populations, non-aneurysmal etiologies of subarachnoid hemorrhage, mycotic and traumatic subarachnoid hemorrhage, and articles regarding tracheostomies.
DATA EXTRACTION
Articles were reviewed by one team member, and interpretation was verified by a second team member.
DATA SYNTHESIS
Thirty-one articles met the inclusion criteria for this review.
CONCLUSIONS
We make recommendations on oxygenation, hypercapnia, PEEP, APRV, ARDS, and intracranial pressure monitoring.
Topics: Humans; Prone Position; Respiration, Artificial; Respiratory Distress Syndrome; Subarachnoid Hemorrhage
PubMed: 32972406
DOI: 10.1186/s13054-020-03269-8 -
Metabolic Syndrome and Related Disorders Dec 2022This study aims to systematically evaluate the association between metabolic syndrome (MS) and pulmonary function through meta-analysis. Electronic databases,... (Meta-Analysis)
Meta-Analysis
This study aims to systematically evaluate the association between metabolic syndrome (MS) and pulmonary function through meta-analysis. Electronic databases, including PubMed, Embase, Web of Science, and Cochrane Library, were systematically searched to obtain articles associated with MS and lung function published before December 31, 2021. According to the including and excluding criteria, certain studies were obtained and data were extracted. The Newcastle Ottawa Scale was used to evaluate the quality of the studies. A pooled standardized mean difference (SMD) was calculated by means of random-effects meta-analysis. Different effect models were used according to the heterogeneity. Meta-regression and sensitivity analyses were performed to examine the possible sources of heterogeneity. The Begg's funnel plot and Egger's test were used to evaluate publication bias. Analyses were performed using Stata MP, version14.0 (StataCorp LP, College Station, TX, USA). A total of 15 studies, involving 10,285 cases of MS and 25,416 cases of control, were included in this meta-analysis on the relationship between MS and forced vital capacity (FVC). The pooled SMD for FVC was -0.247 (95% CI = -0.327 to -0.2167, < 0.001) using random effect model, indicating the decrease of FVC in the patients with MS. In the same studies, the pooled SMD for forced expiratory volume in 1 sec (FEV) was -0.205 (95% CI = -0.3278 to -0.133, < 0.001), indicating the decrease of FEV also existed in the MS cases. A total of 13 studies, involving 8167 cases of MS and 19,788 cases of control, were included in this meta-analysis on the relationship between MS and FEV/FVC. The pooled SMD for FEV/FVC was 0.011 (95% CI = -0.072 to 0.093, = 0.798) using random effect model, indicating that there was no significant difference between the patients with MS and the control. After introducing the diastolic blood pressure and glycemia into the regression model of the relationship between MS and FVC, the variance of the studies (tau2) decreased from 0.0190 to 0.006694 and 0.007205, which could explain 66.70% and 78.04% of the sources of heterogeneity, and the values were 0.038 and 0.023. The results suggested that hypertension (diastolic pressure) and hyperglycemia were the factors linked to the heterogeneity among the included studies on both FVC and FEV. The Begg's funnel plot and Egger's test both showed no evidence of publication bias. Our results show that FVC and FEV decrease in MS patients, while FEV/FVC has no significant difference compared with the control group. It indicates that the patients with MS have restrictive ventilatory functional disturbance. Meta-regression analysis suggests that hypertension (diastolic pressure) and hyperglycemia are the factors linked to the heterogeneity among the included studies on both FVC and FEV.
Topics: Humans; Metabolic Syndrome; Lung; Forced Expiratory Volume; Hypertension; Hyperglycemia
PubMed: 36125502
DOI: 10.1089/met.2022.0045 -
BMC Pulmonary Medicine Jan 2021Bilirubin is a potent antioxidant and higher serum bilirubin levels have been associated with improved COPD outcomes. We performed a systematic review to evaluate the...
BACKGROUND
Bilirubin is a potent antioxidant and higher serum bilirubin levels have been associated with improved COPD outcomes. We performed a systematic review to evaluate the association between serum bilirubin levels and lung function (FEV), prevalence/incidence of COPD, acute exacerbations of COPD, respiratory health status, and mortality.
METHODS
MEDLINE® and Embase were searched using Ovid® (search updated October 1st, 2019). We included studies that measured serum bilirubin levels and outcomes of interest in adults with or without underlying lung disease. We excluded studies of those with liver disease or drug-induced elevations in bilirubin. We used the Newcastle-Ottawa scale to assess individual study risk of bias (ROB) and the US Agency for Healthcare Research and Quality-Evidence Based Practice tool to assess overall strength of evidence (SOE). Two authors independently determined eligibility, performed data abstraction, assessed ROB, and determined SOE.
RESULTS
Thirteen studies (5 low risk of bias, 3 moderate and 5 high risk) were included. We found low strength of evidence for the association between higher bilirubin levels and lower risk of acute exacerbations of COPD (2 studies), mortality (3 studies), COPD diagnosis (4 studies), and lung function (FEV) (8 studies). We found insufficient evidence on the relationship between serum bilirubin and respiratory health status/exercise capacity (1 study) and airflow obstruction (FEV/FVC ratio) (4 studies).
CONCLUSION
Higher bilirubin levels may be associated with lower mortality and improved COPD outcomes. Randomized trials are needed to evaluate the effect of medications that raise serum bilirubin on COPD outcomes. PROSPERO registration: CRD42019145747.
Topics: Antioxidants; Bilirubin; Disease Progression; Humans; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests
PubMed: 33472602
DOI: 10.1186/s12890-021-01395-9 -
Journal of Vascular Surgery. Venous and... Mar 2024The aim of this study was to determine the association between the duration of systemic anticoagulation therapy (ACT) and the risk of further venous thromboembolism... (Meta-Analysis)
Meta-Analysis Review
A systematic review and meta-analysis for the association between duration of anticoagulation therapy and the risk of venous thromboembolism in patients with lower limb superficial venous thrombosis.
OBJECTIVE
The aim of this study was to determine the association between the duration of systemic anticoagulation therapy (ACT) and the risk of further venous thromboembolism (VTE) in patients with superficial venous thrombosis (SVT).
METHODS
A systematic review and meta-analysis were performed using searches of Medline and Cochrane Library databases in September 2023. Papers that provided VTE incidence within mid-term follow-up of ≥45 days in patients who received any ACT were included. Patients were categorized into subgroups according to the course of treatment: (1) no ACT (0 days); (2) ACT of ≤14 days; (3) ACT of 15 to 30 days; (4) ACT of 31 to 45 days; and (5) ACT of >45 days. Reported events were transformed to events per 100 patient-years, and a random-effects model was used to calculate pooled rates for proportions. The primary outcome (VTE) was a combination of SVT progression or recurrence with the occurrence of deep vein thrombosis (DVT) and pulmonary embolism (PE). Secondary outcomes included major and clinically relevant non-major or minor bleeding.
RESULTS
Twenty-four studies (10 randomized controlled trials and 14 cohort studies) combining outcomes in 12,341 patients were included in the quantitative synthesis. Minimum VTE and SVT recurrence or progression rates were observed with the ACT duration of 31 to 45 days of 16.2 (95% confidence interval [CI], 10.4-23.3) and 8.2 (95% CI, 3.1-15.8) events per 100 patient-years, respectively. Minimum DVT and PE rates observed with the treatment duration of 15 to 30 days were 5.5 (95% CI, 2.8-9.1) and 0.9 (95% CI, 0.5-1.3) events per 100 patient-years, respectively. Short-term treatment of ≤14 days was associated with the highest rates of VTE of 59.7 (95% CI, 37.7-86.4), DVT of 13.7 (95% CI, 9.6-18.4), and PE of 3.1 (95% CI, 1.4-5.6) events per 100 patient-years. Major bleeding rates were unrelated to the duration of ACT and did not exceed 0.5 events per 100 patient-years. The highest rate of clinically relevant non-major or minor bleeding was observed with ACT duration of 31 to 45 days of 14.2 (95% CI, 5.5-26.8) events per 100 patient-years. The most common risk factors for VTE included male sex, cancer, personal history of DVT, PE, or SVT, and thrombosis of non-varicose veins.
CONCLUSIONS
Prolonged systemic anticoagulation is associated with the tendency to decrease VTE rates in patients with lower limb SVT.
Topics: Humans; Male; Venous Thromboembolism; Anticoagulants; Venous Thrombosis; Pulmonary Embolism; Lower Extremity; Hemorrhage; Randomized Controlled Trials as Topic
PubMed: 38008180
DOI: 10.1016/j.jvsv.2023.101726 -
Revue Des Maladies Respiratoires Jan 2020Cocaine can be responsible for many psychiatric and/or somatic disorders. The aim of this systematic literature review of data was to expose relations between cocaine...
Cocaine can be responsible for many psychiatric and/or somatic disorders. The aim of this systematic literature review of data was to expose relations between cocaine use and pulmonary complications. Cocaine can be responsible for acute respiratory symptoms (cough, black sputum, hemoptysis, dyspnea, wheezing, chest pain) and for various pulmonary disorders including barotrauma (pneumothorax, pneumomediastinum, subcutaneous emphysema, pneumopericardium), airway damage, asthma, bronchiolitis obliterans with organizing pneumonia, acute pulmonary edema, alveolar hemorrhage, alveolar pneumonia with carbonaceous material, bullous emphysema, acute eosinophilic pneumonia, pulmonary granulomatosis caused by talc or cellulose, interstitial pneumonitis and pulmonary fibrosis, vasculitis, pulmonary hypertension, pulmonary embolism and pulmonary infarction, mycotic pulmonary arterial aneurysms, septic emboli, aspiration pneumonia, community-acquired pneumonia, HIV-related opportunistic infections, latent tuberculosis infection, pulmonary tuberculosis, lung cancer and crack lung. Some of these complications are serious and may have a fatal outcome. Pulmonary function tests, thoracic tomodensitometry, bronchial fibroscopy with bronchoalveolar lavage and lung scintigraphy may be an aid to the diagnosis of these pulmonary compications. Cocaine use must be sought in case of respiratory symptoms in young persons.
Topics: Cocaine; Cocaine-Related Disorders; Drug Users; Humans; Lung Diseases
PubMed: 31883817
DOI: 10.1016/j.rmr.2019.11.641 -
The Cochrane Database of Systematic... Oct 2019Persistent pulmonary hypertension of the newborn (PPHN) is a disease entity that describes a physiology in which there is persistence of increased pulmonary arterial... (Review)
Review
BACKGROUND
Persistent pulmonary hypertension of the newborn (PPHN) is a disease entity that describes a physiology in which there is persistence of increased pulmonary arterial pressure. PPHN is characterised by failure to adapt to a functional postnatal circulation with a fall in pulmonary vascular resistance. PPHN is responsible for impairment in oxygenation and significant neonatal mortality and morbidity. Prostanoids and their analogues may be useful therapeutic interventions due to their pulmonary vasodilatory and immunomodulatory effects.
OBJECTIVES
Primary objective• To determine the efficacy and safety of prostanoids and their analogues (iloprost, treprostinil, and beraprost) in decreasing mortality and the need for extracorporeal membrane oxygenation (ECMO) among neonates with PHSecondary objective• To determine the efficacy and safety of prostanoids and their analogues (iloprost, treprostinil, and beraprost) in decreasing neonatal morbidity (necrotizing enterocolitis (NEC), chronic lung disease (CLD), retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), length of hospital stay, and duration of mechanical ventilation) and improving neurodevelopmental outcomes among neonates with PHComparisons• Prostanoids and their analogues at any dosage or duration used to treat PPHN versus 'standard treatment without these agents', placebo, or inhaled nitric oxide (iNO) therapy• Prostanoids and their analogues at any dosage or duration used to treat refractory PPHN as an 'add-on' therapy to iNO versus iNO alone SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 9), MEDLINE via PubMed (1966 to 16 September 2018), Embase (1980 to 16 September 2018), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 16 September 2018). We also searched clinical trials databases, conference proceedings of the Pediatric Academic Societies (1990 to 16 September 2018), and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials. We contacted authors who have published in this field as discerned from the reference lists of identified clinical trials and review authors' personal files.
SELECTION CRITERIA
Randomized and quasi-randomized controlled trials evaluating prostanoids or their analogues (at any dose, route of administration, or duration) used in neonates at any gestational age less than 28 days' postnatal age for confirmed or suspected PPHN.
DATA COLLECTION AND ANALYSIS
We used the standard methods of Cochrane Neonatal to conduct a systematic review and to assess the methodological quality of included studies (neonatal.cochrane.org/en/index.html). Three review authors independently assessed the titles and abstracts of studies identified by the search strategy and obtained full-text versions for assessment if necessary. We designed forms for trial inclusion or exclusion and for data extraction. We planned to use the GRADE approach to assess the quality of evidence.
MAIN RESULTS
We did not identify any eligible neonatal trials evaluating prostanoids or their analogues as sole agents in the treatment of PPHN.
AUTHORS' CONCLUSIONS
Implications for practiceCurrently, no evidence shows the use of prostanoids or their analogues as pulmonary vasodilators and sole therapeutic agents for the treatment of PPHN in neonates (age 28 days or less).Implications for researchThe safety and efficacy of different preparations and doses and routes of administration of prostacyclins and their analogues in neonates must be established. Well-designed, adequately powered, randomized, multi-center trials are needed to address the efficacy and safety of prostanoids and their analogues in the treatment of PPHN. These trials should evaluate long-term neurodevelopmental and pulmonary outcomes, in addition to short-term outcomes.
PubMed: 31573068
DOI: 10.1002/14651858.CD012963.pub2 -
Journal of Vascular Surgery. Venous and... Jul 2020Whereas the internal jugular vein is the most common site of thrombosis in patients with deep venous thrombosis (DVT) of the upper extremity, the association between...
OBJECTIVE
Whereas the internal jugular vein is the most common site of thrombosis in patients with deep venous thrombosis (DVT) of the upper extremity, the association between internal jugular vein thrombus and pulmonary embolism (PE) has not been clearly characterized. The objective of this paper was to determine the risk of embolization of an isolated internal jugular vein thrombus causing a clinically overt PE, with the secondary objective of assessing the value of therapeutic anticoagulation in patients with isolated internal jugular vein thrombosis (IJVT) in improving clinical outcomes.
METHODS
The National Center for Biotechnology Information, Cochrane Library, Web of Science, and Cumulative Index to Nursing and Allied Health Literature were searched for articles. The relevant articles included were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were included if they specifically examined incidence of IJVT and incidence of PE and were excluded if they did not report on these rates specifically or failed to specify the exact site of upper extremity DVT.
RESULTS
Of the 274 articles screened, 25 were selected for full review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses inclusion criteria. Seven of those provided adequate data and were included in the review. There were only two studies demonstrating IJVT before PE that could probably establish causality, but this might be confounded by the presence of concomitant upper extremity DVT in one of the cases and radiologic findings compatible with resolving PE in another that might have preceded the presence of internal jugular vein thrombus. In the patients who were found to have PE in the setting of IJVT, the overall observed mortality attributed to PE was low. In specific studies, the use of anticoagulation did not reduce the mortality in those with isolated IJVT or affect the rate of thrombus resolution while carrying the risk of bleeding complications in these patients, who often have severe comorbidities.
CONCLUSIONS
Despite the proximity of the jugular vein to the right side of the heart and the pulmonary vasculature, there is little proof of propagation of the thrombus to cause a clinically overt PE. Whereas current practice is to treat the patients with IJVT in the same way as patients with lower extremity DVTs are treated, the lack of any survival benefit in those with isolated IJVT and the risk of bleeding complications warrant further studies to characterize the need of medical management in this population of patients.
Topics: Anticoagulants; Hemorrhage; Humans; Incidence; Jugular Veins; Pulmonary Embolism; Risk Assessment; Risk Factors; Treatment Outcome; Venous Thrombosis
PubMed: 32321692
DOI: 10.1016/j.jvsv.2020.03.003 -
Journal of Orthopaedics and... Jan 2024Several clinical investigations have compared different pharmacologic agents for the prophylaxis of venous thromboembolism (VTE). However, no consensus has been reached.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several clinical investigations have compared different pharmacologic agents for the prophylaxis of venous thromboembolism (VTE). However, no consensus has been reached. The present investigation compared enoxaparin, fondaparinux, aspirin and non-vitamin K antagonist oral anticoagulants (NOACs) commonly used as prophylaxis following total hip arthroplasty (THA). A Bayesian network meta-analysis was performed, setting as outcomes of interest the rate of deep venous thrombosis (DVT), pulmonary embolism (PE) and major and minor haemorrhages.
METHODS
This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension statement for reporting systematic reviews incorporating network meta-analyses of healthcare interventions. All randomised controlled trials (RCTs) comparing two or more drugs used for the prophylaxis of VTE following THA were accessed. PubMed, Web of Science and Google Scholar databases were accessed in March 2023 with no time constraint.
RESULTS
Data from 31,705 patients were extracted. Of these, 62% (19,824) were women, with age, sex ratio, and body mass index (BMI) being comparable at baseline. Apixaban 5 mg, fondaparinux, and rivaroxaban 60 mg were the most effective in reducing the rate of DVT. Dabigatran 220 mg, apixaban 5 mg, and aspirin 100 mg were the most effective in reducing the rate of PE. Apixaban 5 mg, ximelagatran 2 mg and aspirin 100 mg were associated with the lowest rate of major haemorrhages, while rivaroxaban 2.5 mg, apixaban 5 mg and enoxaparin 40 mg were associated with the lowest rate of minor haemorrhages.
CONCLUSION
Administration of apixaban 5 mg demonstrated the best balance between VTE prevention and haemorrhage control following THA. Level of evidence Level I, network meta-analysis of RCTs.
Topics: Female; Humans; Male; Arthroplasty, Replacement, Hip; Aspirin; Enoxaparin; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Network Meta-Analysis; Rivaroxaban; Venous Thromboembolism
PubMed: 38194191
DOI: 10.1186/s10195-023-00742-2 -
Journal of Neurosurgical Anesthesiology Oct 2021Aneurysmal subarachnoid hemorrhage (aSAH) often causes cardiopulmonary dysfunction. Therapeutic strategies can be guided by standard (invasive arterial/central venous... (Meta-Analysis)
Meta-Analysis
Aneurysmal subarachnoid hemorrhage (aSAH) often causes cardiopulmonary dysfunction. Therapeutic strategies can be guided by standard (invasive arterial/central venous pressure measurements, fluid balance assessment), and/or advanced (pulse index continuous cardiac output, pulse dye densitometry, pulmonary artery catheterization) hemodynamic monitoring. We conducted a systematic review and meta-analysis of the literature to determine whether standard compared with advanced hemodynamic monitoring can improve patient management and clinical outcomes after aSAH. A literature search was performed for articles published between January 1, 2000 and January 1, 2019. Studies involving aSAH patients admitted to the intensive care unit and subjected to any type of hemodynamic monitoring were included. A total of 14 studies were selected for the qualitative synthesis and 3 randomized controlled trials, comparing standard versus advanced hemodynamic monitoring, for meta-analysis. The incidence of delayed cerebral ischemia was lower in the advanced compared with standard hemodynamic monitoring group (relative risk [RR]=0.71, 95% confidence interval [CI]=0.52-0.99; P=0.044), but there were no differences in neurological outcome (RR=0.83, 95% CI=0.64-1.06; P=0.14), pulmonary edema onset (RR=0.44, 95% CI=0.05-3.92; P=0.46), or fluid intake (mean difference=-169 mL; 95% CI=-1463 to 1126 mL; P=0.8) between the 2 groups. In summary, this systematic review and meta-analysis found only low-quality evidence to support the use of advanced hemodynamic monitoring in selected aSAH patients. Because of the small number and low quality of studies available for inclusion in the review, further studies are required to investigate the impact of standard and advanced hemodynamic monitoring-guided management on aSAH outcomes.
Topics: Brain Ischemia; Cardiac Output; Central Venous Pressure; Hemodynamic Monitoring; Humans; Subarachnoid Hemorrhage
PubMed: 32011413
DOI: 10.1097/ANA.0000000000000679 -
American Journal of Obstetrics and... Apr 2024This study aimed to provide procedure-specific estimates of the risk of symptomatic venous thromboembolism and major bleeding in the absence of thromboprophylaxis,... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to provide procedure-specific estimates of the risk of symptomatic venous thromboembolism and major bleeding in the absence of thromboprophylaxis, following gynecologic cancer surgery.
DATA SOURCES
We conducted comprehensive searches on Embase, MEDLINE, Web of Science, and Google Scholar for observational studies. We also reviewed reference lists of eligible studies and review articles. We performed separate searches for randomized trials addressing effects of thromboprophylaxis and conducted a web-based survey on thromboprophylaxis practice.
STUDY ELIGIBILITY CRITERIA
Observational studies enrolling ≥50 adult patients undergoing gynecologic cancer surgery procedures reporting absolute incidence for at least 1 of the following were included: symptomatic pulmonary embolism, symptomatic deep vein thrombosis, symptomatic venous thromboembolism, bleeding requiring reintervention (including reexploration and angioembolization), bleeding leading to transfusion, or postoperative hemoglobin <70 g/L.
METHODS
Two reviewers independently assessed eligibility, performed data extraction, and evaluated risk of bias of eligible articles. We adjusted the reported estimates for thromboprophylaxis and length of follow-up and used the median value from studies to determine cumulative incidence at 4 weeks postsurgery stratified by patient venous thromboembolism risk factors. The GRADE approach was applied to rate evidence certainty.
RESULTS
We included 188 studies (398,167 patients) reporting on 37 gynecologic cancer surgery procedures. The evidence certainty was generally low to very low. Median symptomatic venous thromboembolism risk (in the absence of prophylaxis) was <1% in 13 of 37 (35%) procedures, 1% to 2% in 11 of 37 (30%), and >2.0% in 13 of 37 (35%). The risks of venous thromboembolism varied from 0.1% in low venous thromboembolism risk patients undergoing cervical conization to 33.5% in high venous thromboembolism risk patients undergoing pelvic exenteration. Estimates of bleeding requiring reintervention varied from <0.1% to 1.3%. Median risks of bleeding requiring reintervention were <1% in 22 of 29 (76%) and 1% to 2% in 7 of 29 (24%) procedures.
CONCLUSION
Venous thromboembolism reduction with thromboprophylaxis likely outweighs the increase in bleeding requiring reintervention in many gynecologic cancer procedures (eg, open surgery for ovarian cancer and pelvic exenteration). In some procedures (eg, laparoscopic total hysterectomy without lymphadenectomy), thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding venous thromboembolism and bleeding.
Topics: Adult; Humans; Female; Anticoagulants; Venous Thromboembolism; Postoperative Complications; Hemorrhage; Thrombosis; Neoplasms
PubMed: 37827272
DOI: 10.1016/j.ajog.2023.10.006