Antithrombotic Therapy for VTE Disease: Compendium and Review of CHEST Guidelines 2012-2021.

The CHEST Antithrombotic Therapy for Venous Thromboembolism Disease evidence-based guidelines are now updated in a more frequent, focused manner. Guidance statements from the most recent full guidelines and two subsequent updates have not been gathered into a single source. An international panel of experts with experience in prior antithrombotic therapy guideline development reviewed the 2012 CHEST antithrombotic therapy guidelines and its two subsequent updates. All guideline statements and their associated patient, intervention, comparator, and outcome questions were assembled. A modified Delphi process was used to select statements considered relevant to current clinical care. The panel further endorsed minor phrasing changes to match the standard language for guidance statements using the modified Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) format endorsed by the CHEST Guidelines Oversight Committee. The panel appended comments after statements deemed as relevant, including suggesting that statements be updated in future guidelines because of interval evidence. We include 58 guidance statements from prior versions of the antithrombotic therapy guidelines, with updated phrasing as needed to adhere to contemporary nomenclature. Statements were classified as strong or weak recommendations based on high-certainty, moderate-certainty, and low-certainty evidence using GRADE methodology. The panel suggested that five statements are no longer relevant to current practice. As CHEST continues to update guidance statements relevant to antithrombotic therapy for VTE disease, this article serves as a unified collection of currently relevant statements from the preceding three guidelines. Suggestions have been made to update specific statements in future publications.

Observational cohort study to validate SEARCH, a novel hierarchical algorithm to define long-term outcomes after pulmonary embolism.

BACKGROUND: Chronic dyspnoea and exercise impairment are common after acute pulmonary embolism (PE) but are not defined and quantified sufficiently to serve as outcomes in clinical trials. The planned project will clinically validate a novel method to determine discrete, clinically meaningful diagnoses after acute PE. The method uses an algorithm entitled SEARCH, for symptom screen, exercise testing, arterial perfusion, resting echocardiography, confirmatory imaging and haemodynamic measurements. SEARCH is a stepwise algorithm that sorts patients by a hierarchical series of dichotomous tests into discreet categories of long-term outcomes after PE: asymptomatic, post-PE deconditioning, symptoms from other causes, chronic thromboembolism with ventilatory inefficiency, chronic thromboembolism with small stroke volume augmentation, chronic thromboembolic disease and chronic thromboembolic pulmonary hypertension. METHODS: The project will test the inter-rater reliability of the SEARCH algorithm by determining whether it will yield concordant post-PE diagnoses when six independent reviewers review the same diagnostic data on 150 patients evaluated at two time points after PE. The project will also determine whether the post-PE diagnoses are stable, according to the SEARCH algorithm, between the first evaluation and the subsequent one 6 months later. IMPLICATIONS: Validation of the SEARCH algorithm would offer clinicians a straightforward method to diagnose post-PE conditions that are rarely distinguished clinically. Their categorisation and definition will allow post-PE conditions to be used as endpoints in clinical trials of acute PE treatment. TRIAL REGISTRATION NUMBER: NCT05568927.

Using statistical techniques to predict dynamic arterial P(CO(2)) in patients with COPD during maximum exercise.

BACKGROUND: P(aCO(2)) as measured during exercise in patients with COPD is poorly predicted (predicted P(aCO(2))) from lung function testing and some noninvasive measurements, such as end-tidal P(CO(2)) (P(ETCO(2))). OBJECTIVE: We performed a number of statistical techniques on P(ETCO(2)) and its interaction with other physiologic variables during exercise testing, in order to improve our ability to predict P(aCO(2)). The estimated P(aCO(2)) as determined from these techniques may therefore be used to contrast the P(ETCO(2)) readings that are measured during an incremental exercise test on a breath-by-breath basis (ie, P(aCO(2)) - P(ETCO(2))), and to identify exercise-induced hypercapnia. METHODS: Forty-seven men with COPD underwent both pulmonary function testing and incremental exercise testing until limited by symptoms. Arterial blood gases and exercise physiological measurements were performed during maximal exercise testing. The prediction equations for P(aCO(2)) were generated using regression techniques with the leave-one-out cross-validation technique. RESULTS: Forty-one patients were included in the final analysis after 6 patients were excluded due to inadequate data collection. The best prediction equation we found was: predicted P(aCO(2)) = 23.71 + P(ETCO(2)) × (0.9-0.01 × D(LCO) -0.04 × V(T)) - 2.61 × SVC - 0.04 × MEP, where D(LCO) is diffusing capacity for carbon monoxide in mL/min/mm Hg, V(T) is tidal volume in L, SVC is slow vital capacity in L, and MEP is maximum expiratory pressure in cm H(2)O. The difference between the measured and predicted P(aCO(2)) at each time point was not statistically significant (all P > .05). The standard errors of the estimated P(aCO(2)) at each time point were 0.91-1.12 mm Hg. CONCLUSIONS: A validated mixed-model regression derived equation yields a predicted P(aCO(2)) trend during exercise that can be helpful when interpreting exercise testing to determine P(aCO(2)) - P(ETCO(2)) and exercise-induced hypercapnia.

Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report.

BACKGROUND: This is the 2nd update to the 9th edition of these guidelines. We provide recommendations on 17 PICO (Population, Intervention, Comparator, Outcome) questions, four of which have not been addressed previously. METHODS: We generate strong and weak recommendations based on high-, moderate-, and low-certainty evidence, using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology. RESULTS: The panel generated 29 guidance statements, 13 of which are graded as strong recommendations, covering aspects of antithrombotic management of VTE from initial management through secondary prevention and risk reduction of postthrombotic syndrome. Four new guidance statements have been added that did not appear in the 9th edition (2012) or 1st update (2016). Eight statements have been substantially modified from the 1st update. CONCLUSION: New evidence has emerged since 2016 that further informs the standard of care for patients with VTE. Substantial uncertainty remains regarding important management questions, particularly in limited disease and special patient populations.

Executive Summary: Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report.

BACKGROUND: This is the 2nd update to the 9th edition of these guidelines. We provide recommendations on 17 PICO (Population, Intervention, Comparator, Outcome) questions, four of which have not been addressed previously. METHODS: We generate strong and weak recommendations based on high-, moderate-, and low-certainty evidence, using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology. RESULTS: The panel generated 29 guidance statements, 13 of which are graded as strong recommendations, covering aspects of antithrombotic management of VTE from initial management through secondary prevention and risk reduction of postthrombotic syndrome. Four new guidance statements have been added that did not appear in the 9th edition (2012) or 1st update (2016). Eight statements have been substantially modified from the 1st update. CONCLUSION: New evidence has emerged since 2016 that further informs the standard of care for patients with VTE. Substantial uncertainty remains regarding important management questions, particularly in limited disease and special patient populations.

Gas exchange detection of right-to-left shunt in dyspneic patients: report of three cases.

We evaluated three patients with undiagnosed complaints of progressive dyspnea. Based on gas-exchange findings as the initial diagnostic tool, the high ventilatory equivalents for CO2, low sustained end-tidal PCO2, hypoxemia, and central cardiovascular dysfunction during cardiopulmonary exercise testing (CPET) suggested that each had significant pulmonary vasculopathy with right-to-left shunting. The diagnoses of Osler-Rendu-Weber syndrome, ventricular septal defect with Eisenmenger's complex, and hepatopulmonary syndrome were later confirmed by pulmonary angiography, cardiac catheterization, and contrast enhanced echocardiography respectively. We suggest that CPET is an appropriate noninvasive tool to begin and guide the evaluation of undiagnosed dyspnea.

Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report.

BACKGROUND: We update recommendations on 12 topics that were in the 9th edition of these guidelines, and address 3 new topics. METHODS: We generate strong (Grade 1) and weak (Grade 2) recommendations based on high- (Grade A), moderate- (Grade B), and low- (Grade C) quality evidence. RESULTS: For VTE and no cancer, as long-term anticoagulant therapy, we suggest dabigatran (Grade 2B), rivaroxaban (Grade 2B), apixaban (Grade 2B), or edoxaban (Grade 2B) over vitamin K antagonist (VKA) therapy, and suggest VKA therapy over low-molecular-weight heparin (LMWH; Grade 2C). For VTE and cancer, we suggest LMWH over VKA (Grade 2B), dabigatran (Grade 2C), rivaroxaban (Grade 2C), apixaban (Grade 2C), or edoxaban (Grade 2C). We have not changed recommendations for who should stop anticoagulation at 3 months or receive extended therapy. For VTE treated with anticoagulants, we recommend against an inferior vena cava filter (Grade 1B). For DVT, we suggest not using compression stockings routinely to prevent PTS (Grade 2B). For subsegmental pulmonary embolism and no proximal DVT, we suggest clinical surveillance over anticoagulation with a low risk of recurrent VTE (Grade 2C), and anticoagulation over clinical surveillance with a high risk (Grade 2C). We suggest thrombolytic therapy for pulmonary embolism with hypotension (Grade 2B), and systemic therapy over catheter-directed thrombolysis (Grade 2C). For recurrent VTE on a non-LMWH anticoagulant, we suggest LMWH (Grade 2C); for recurrent VTE on LMWH, we suggest increasing the LMWH dose (Grade 2C). CONCLUSIONS: Of 54 recommendations included in the 30 statements, 20 were strong and none was based on high-quality evidence, highlighting the need for further research.

A retrospective analysis of the management of parapneumonic empyemas in a county teaching facility from 1992 to 2004.

OBJECTIVES: To characterize how patients with empyemas are managed initially at our facility and to determine how "less aggressive" treatments (eg, no drainage, repeat thoracentesis, or tube thoracostomy) affect short-term outcomes (ie, inpatient mortality and the need for a second intervention) compared to "more aggressive" treatments (eg, intrapleural fibrinolytic agents, video-assisted thoracoscopic surgery, or other surgery). We will also assess whether earlier diagnosis, earlier antibiotic treatment, fewer patient comorbidities, and consulting appropriate services improve mortality. DESIGN: Retrospective chart analysis. SETTING: County teaching hospital in Los Angeles, CA. PATIENTS: Seventy-two adult inpatients with parapneumonic empyemas. INTERVENTIONS: Mortality and the need for second intervention rates were calculated and compared with data published in the 2000 American College of Chest Physicians consensus statement on the management of parapneumonic effusions using the Fisher exact test. Comparisons were made between empyema survivors and nonsurvivors using t tests and chi(2) tests. RESULTS: All 72 patients were managed with less aggressive initial treatments. There were no differences in mortality when our patients were compared to the less aggressive group from the literature (6% vs 9%, respectively; p = 0.40; relative risk, 0.6; 95% confidence interval [CI], 0.23 to 1.62) or the more aggressive group from the literature (6% vs 3%, respectively; p = 0.29; relative risk, 1.8; 95% CI, 0.64 to 5.23). There was no difference between the second intervention rate of our patients and that of the less aggressive group from the literature (47% vs 43%, respectively; p = 0.47; relative risk, 1.1; 95% CI, 0.86 to 1.42), although there was a difference when compared to the more aggressive group (47% vs 11%, respectively; p < 0.0001; relative risk, 4.5; 95% CI, 3.20 to 6.31). There were no statistically significant differences in time of diagnosis, the timing of antibiotic treatment, the number of patient comorbidities, or the number of services consulted when survivors and nonsurvivors from the study were compared. CONCLUSIONS: Patients with empyemas at our hospital are treated with less aggressive initial treatments and have a higher second intervention rate when compared to patients described in the literature who were initially managed with more aggressive treatments.

Ventilation and exercise performance after phrenic nerve and multiple intercostal nerve transfers for avulsed brachial plexus injury.

BACKGROUND: Diaphragmatic excursion, lung function, exercise performance, and clinical symptoms have not been previously described in patients after phrenic nerve transfer (PNT) and/or multiple intercostal nerve transfer (MIT) for the repair of avulsed brachial plexus injury (ABPI) to prevent functional musculoskeletal impairment in the shoulder. SETTING: A university-based hospital. METHODS: Dyspnea scores, chest ultrasonography to assess diaphragmatic excursion, and pulmonary function testing were performed to assess ventilation in patients sustaining trauma to their brachial plexus. In addition, cardiopulmonary exercise testing was also performed. These studies were obtained prior to surgical intervention, and were repeated postoperatively at 6, 12, 18, 24, and 36 months. The results obtained preoperatively were compared to those obtained throughout the postoperative monitoring period. RESULTS: This study demonstrates that the PNT-MIT procedure results in permanent ipsilateral diaphragmatic paralysis accompanied by an approximately 8% decrease in inspiratory capacity, FVC, and total lung capacity. There was also an 11% increase in diffusing capacity noted during the period between 6 months and 3 years after PNT-MIT procedure. Despite these measurable changes in lung function, the patients reported amelioration of their dyspnea complaint within 6 months of undergoing this procedure, which was due mainly to an improvement in their cardiovascular exercise performance related to increased daily activity. CONCLUSIONS: This study demonstrates that the PNT-MIT procedure is a safe method for the restoration of drop shoulder incurred by ABPI. This surgery has an impact on measurable diaphragmatic and lung function but with minimal impact in terms of postoperative clinical symptoms and exercise performance.

Predicting continuous positive airway pressure from a modified split-night protocol in moderate to severe obstructive sleep apnea-hypopnea syndrome.

BACKGROUND: Most split-night sleep (SNS) studies have enrolled Caucasian patients with moderate-to-severe obstructive sleep apnea-hypopnea syndrome (OSAHS), with different apnea-hypopnea index (AHI) criteria for diagnosis and successful CPAP titration from the standard full-night study (FNS). This study aimed to describe a shortened diagnostic SNS in the Taiwanese population using diagnostic and CPAP therapeutic criteria identical to the standard FNS, and to generate a predictive equation for effective CPAP (Peff) titration. METHODS: A total of 418 patients with moderate-to-severe OSAHS were enrolled in this study. The duration of the diagnostic SNS was shortened to approximately 1-2 hours. The diagnostic accuracy and the success rate of CPAP titration in SNS were evaluated and a statistical model for Peff was built. The accuracy of the predictive equation was validated in another 127 patients. RESULTS: Eighty-nine percent of patients with moderate-to-severe OSAHS diagnosed in the preceding FNS yielded the same grade of OSAHS in SNS. These reproducible patients were more severe, with 88% attaining successful CPAP titration in SNS. The predictive Peff=1.98+0.184xBMI+0.01xAHISNS +0.016xDISNS (R2=0.28, p<0.0001) where BMI was the body mass index and DI the desaturation index. The | predictive Peff- Peff | was within 2 cm H(2)O in 84% of the study group and 73% of the validation group. CONCLUSION: The modified split-night protocol and the predictive equation for CPAP can be useful in Taiwanese patients with moderate-to-severe OSAHS. Our findings may shorten the waiting time for polysomnography.

The utility of open lung biopsy in patients with diffuse pulmonary infiltrates as related to respiratory distress, its impact on decision making by urgent intervention, and the diagnostic accuracy based on the biopsy location.

Patients with diffuse pulmonary infiltrates (DPI), especially those who present with respiratory distress (RD), may benefit from early open lung biopsy (OLB) to guide management. Benefits of urgent OLB would be expected by saving the time to reach accurate specific diagnoses. The objectives of this study were (1) to evaluate the impact of OLB between patients presenting with and without RD, (2) to focus on the impact of an urgent OLB as compared to an elective OLB, and (3) to compare the different yields of specific diagnoses in the middle lobe or lingula as compared to the other lobes. Thirty-four patients (17 patients presented with RD and 17 patients did not) with an average age of 43 years who presented with DPI were selected to undergo an OLB. An urgent OLB was performed in 11 unselected patients. Twelve specimens from the middle lobe or lingula were compared to 25 specimens from the other lobes. The impact of the OLB results on decision making did not differ significantly between patients with and without RD. Patients with RD suffered a higher in-hospital mortality rate, OLB-related complications, and longer mechanical ventilation requirements than the patients without RD. The impact on decision making and complications between urgent OLB and elective OLB was comparable. The diagnostic yield from biopsy sites in the middle lobe or lingula resembled those specimens from the other lobes. The authors conclude that OLB may play a role in decision making for patients with DPI. However, OLB makes no difference in decision making between patients with and without RD. Patients with RD undergoing OLB procedures may suffer a poorer outcome. Urgent OLB may not benefit patients with DPI in decision making. The biopsy site does not appear to affect the accuracy of the diagnostic yield from an OLB procedure.