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

The American College of Chest Physicians (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 (ie, 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 currenrtly relevant statements from the preceding three guidelines. Suggestions have been made to update specific statements in future publications.

Holistic Admissions at UC Davis-Journey Toward Equity.

This Viewpoint discusses what higher education institutions can learn from UC Davis when it comes to ensuring equity for their students now that the US Supreme Court has eliminated race-conscious college admissions.

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.

Society of Interventional Radiology Clinical Practice Guideline for Inferior Vena Cava Filters in the Treatment of Patients with Venous Thromboembolic Disease: Developed in collaboration with the American College of Cardiology, American College of Chest Physicians, American College of Surgeons Committee on Trauma, American Heart Association, Society for Vascular Surgery, and Society for Vascular Medicine.

PURPOSE: To provide evidence-based recommendations on the use of inferior vena cava (IVC) filters in the treatment of patients with or at substantial risk of venous thromboembolic disease. MATERIALS AND METHODS: A multidisciplinary expert panel developed key questions to address in the guideline, and a systematic review of the literature was conducted. Evidence was graded based on a standard methodology, which was used to inform the development of recommendations. RESULTS: The systematic review identified a total of 34 studies that provided the evidence base for the guideline. The expert panel agreed on 18 recommendations. CONCLUSIONS: Although the evidence on the use of IVC filters in patients with or at risk of venous thromboembolic disease varies in strength and quality, the panel provides recommendations for the use of IVC filters in a variety of clinical scenarios. Additional research is needed to optimize care for this patient population.

Pharmacotherapeutic management of asthma in the elderly patient.

INTRODUCTION: Asthma is a heterogeneous syndrome with variable phenotypes. Reversible airway obstruction and airway hyper-responsiveness often with an atopic or eosinophilic component is common in the elderly asthmatic. Asthma chronic obstructive pulmonary disease overlap syndrome (ACOS), a combination of atopy-mediated airway hyper-responsiveness and a history of smoking or other environmental noxious exposures, can lead to some fixed airway obstruction and is also common in elderly patients. Little specific data exist for the treating the elderly asthmatic, thus requiring the clinician to extrapolate from general adult data and asthma treatment guidelines. AREAS COVERED: A stepwise approach to pharmacotherapy of the elderly patient with asthma and ACOS is offered and the literature supporting the use of each class of drugs reviewed. EXPERT OPINION: Inhaled, long-acting bronchodilators in combination with inhaled corticosteroids represent the backbone of treatment for the elderly patient with asthma or ACOS . Beyond these medications used as direct bronchodilators and topical anti-inflammatory agents, a stepwise approach to escalation of therapy includes multiple options such as oral leukotriene receptor antagonist or 5-lipoxygense inhibitor therapy, oral phosphodiesterase inhibitors, systemic corticosteroids, oral macrolide antibiotics and if evidence of eosinophilic/atopic component disease exists then modifying monoclonal antibody therapies.

The pharmacological management of asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS).

Introduction: Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) is a disease phenotype that shares T helper lymphocyte cell Th1/neutrophilic/non-Type-2 Inflammation pathways thought to be key in COPD and Th2/eosinophilic/Type-2 inflammatory pathways of asthma. The pharmacology of treating ACOS is challenging in severe circumstances.Areas covered: This review evaluates the stepwise treatment of ACOS using pharmacological treatments used in both COPD and asthma. The most common medications involve the same inhalers used to treat COPD and asthma patients. Advanced stepwise therapies for ACOS patients are based on patient characteristics and biomarkers. Very few clinical trials exist that focus specifically on ACOS patients.Expert opinion: After inhalers, advanced therapies including phosphodiesterase inhibitors, macrolides, N-acetylcysteine and statin therapy for those ACOS patients with a COPD appearance and exacerbations are available. In atopic ACOS patients with exacerbations, advanced asthma therapies (leukotriene receptor antagonists and synthesis blocking agents.) are used. ACOS patients with elevated blood eosinophil/IgE levels are considered for immunotherapy or therapeutic monoclonal antibodies blocking specific Th2/Type-2 interleukins or IgE. Symptom control, stabilization/improvement in pulmonary function and reduced exacerbations are the metrics of success. More pharmacological trials of ACOS patients are needed to better understand which patients benefit from specific treatments.Abbreviations: 5-LOi: 5-lipoxygenase inhibitor; ACOS: asthma - COPD overlap syndrome; B2AR: Beta2 adrenergic receptors; cAMP: cyclic adenosine monophosphate; cGMP: cyclic guanosine monophosphate; CI: confidence interval; COPD: chronic obstructive pulmonary disease; CRS : chronic rhinosinusitis; cys-LT: cysteinyl leukotrienes; DPI: dry powder inhaler; EMA: European Medicines Agency; FDA: US Food and Drug Administration; FDC: fixed-dose combination; FeNO: exhaled nitric oxide; FEV1: forced expiratory volume in one second; FVC: forced vital capacity; GM-CSF: granulocyte-macrophage colony-stimulating factor; ICS : inhaled corticosteroids; IL: interleukin; ILC2: Type 2 innate lymphoid cells; IP3: Inositol triphosphate; IRR: incidence rate ratio; KOLD: Korean Obstructive Lung Disease; LABA: long-acting B2 adrenergic receptor agonist; LAMA: long-acting muscarinic receptor antagonist; LRA: leukotriene receptor antagonist; LT: leukotrienes; MDI: metered-dose inhalers; MN: M-subtype muscarinic receptors; MRA: muscarinic receptor antagonist; NAC: N-acetylcysteine; NEB: nebulization; OR: odds ratio; PDE: phosphodiesterase; PEFR: peak expiratory flow rate; PGD2: prostaglandin D2; PRN: as needed; RR: risk ratio; SABA: short-acting B2 adrenergic receptor agonist; SAMA: short-acting muscarinic receptor antagonist; SDMI: spring-driven mist inhaler; Th1: T helper cell 1 lymphocyte; Th2: T helper cell 2 lymphocytes; TNF-α: tumor necrosis factor alpha; US : United States.

A 65-Year-Old Man with Pulmonary Opacities and Worsening Cough.

CASE PRESENTATION: A 65-year-old man was referred for evaluation of several years of chest congestion and cough productive of yellow sputum as well as recently noted abnormalities on chest imaging. He denied dyspnea, weight loss, fevers, chills, or hemoptysis. He had no history of systemic illness, pneumonia, other respiratory illness, gastroesophageal reflux, or sinusitis. He had a remote smoking history. He worked as a railroad conductor and had occupational exposure to asbestos, as well as to other uncharacterized dusts and fumes. The patient spent most of his life in Washington and California and regularly traveled through the California Central Valley. Other travel history included trips to Southeast Asia, Iceland, and Europe in the remote past. The patient had one dog but no exposure to other animals. His only medication was loratadine, taken daily for allergic rhinitis. He applied petroleum jelly to his nares nightly to moisturize his nasal passages.

Leading Change and Negotiation Strategies for Division Leaders in Clinical Medicine.

Most physician leaders assume their administrative role based on past achievements but with very little leadership training. In this article, leaders of the Association of Pulmonary, Critical Care, and Sleep Division Directors describe two leadership skills that are often required to effectively lead in a clinical division at an academic or community hospital setting: leading change and negotiation strategy. We adopted our discussion from the business sector and refined the approaches through our own experiences to help division leaders in leading a successful team, whether as a division chief, residency or fellowship program director, or a clinical service director. Leading any change project may include an eight-step process, starting with creating a sense of urgency and completing with anchoring the change to the organizational culture. We then review negotiation strategies, comparing positional bargaining vs principled negotiation, to create more changes and continuing growth for the division. Finally, we discuss the importance of emotional intelligence, exemplary leadership practices, and self-development that the division leader should embrace.

Evidence-based review of data on the combination inhaler umeclidinium/vilanterol in patients with COPD.

The use of inhaled, fixed-dose, long-acting muscarinic antagonists (LAMA) combined with long-acting, beta2-adrenergic receptor agonists (LABA) has become a mainstay in the maintenance treatment of chronic obstructive pulmonary disease (COPD). One of the fixed-dose LAMA/LABA combinations is the dry powder inhaler (DPI) of umeclidinium bromide (UMEC) and vilanterol trifenatate (VI) (62.5 µg/25 µg) approved for once-a-day maintenance treatment of COPD. This paper reviews the use of fixed-dose combination LAMA/LABA agents focusing on the UMEC/VI DPI inhaler in the maintenance treatment of COPD. The fixed-dose combination LAMA/LABA inhaler offers a step beyond a single inhaled maintenance agent but is still a single device for the COPD patient having frequent COPD exacerbations and persistent symptoms not well controlled on one agent. Currently available clinical trials suggest that the once-a-day DPI of UMEC/VI is well-tolerated, safe and non-inferior or better than other currently available inhaled fixed-dose LAMA/LABA combinations for COPD.

The Salford Lung Study: a pioneering comparative effectiveness approach to COPD and asthma in clinical trials.

The Salford Lung Study (SLS) of patients with asthma and chronic obstructive pulmonary disease (COPD) is a practical, community-based, randomized, open-label pragmatic study on the efficacy and safety of the once-daily dry powder inhaler that combines the inhaled corticosteroid fluticasone furoate (FF) with the long-acting beta2 agonist vilanterol (VI). The asthma component of the SLS is not yet reported but the COPD component, done over a 12-month period, found a statistically significant 8.4% reduction in COPD exacerbations when compared to usual care. No differences in adverse events, including serious adverse events and pneumonia, were noted. The importance of real-world findings, such as those found in the SLS COPD trial with inhaled FF/VI, is discussed in comparison to classical randomized controlled trials (RCTs) with inhaled FF/VI in COPD patients. The real-world, community-based pragmatic RCT like the SLS provides additional generalizable data with direct clinical applicability and potential usefulness in the development of practice guidelines. The results from the SLS, along with those of large and small RCTs, are supportive of the use of once-daily FF/VI in COPD maintenance therapy.

LINX®, a novel treatment for patients with refractory asthma complicated by gastroesophageal reflux disease: a case report.

BACKGROUND: Gastroesophageal reflux disease is one of the most common comorbidities in patients with asthma. Gastroesophageal reflux disease can be linked to difficult-to-control asthma. Current management includes gastric acid suppression therapy and surgical antireflux procedures. The LINX® procedure is a novel surgical treatment for patients with gastroesophageal reflux disease refractory to medical therapy. To the best of our knowledge, we report the first case of successful treatment of refractory asthma secondary to gastroesophageal reflux disease using the LINX® procedure. CASE PRESENTATION: Our patient was a 22-year-old white woman who met the American Thoracic Society criteria for refractory asthma that had remained poorly controlled for 5 years despite progressive escalation to step 6 treatment as recommended by National Institutes of Health-National Asthma Education and Prevention Program guidelines, including high-dose oral corticosteroids, high-dose inhaled corticosteroid plus long-acting ß2-agonist, leukotriene receptor antagonist, and monthly omalizumab. Separate trials with azithromycin therapy and roflumilast did not improve her asthma control, nor did bronchial thermoplasty help. Additional consultations with two other university health systems left the patient with few treatment options for asthma, which included cyclophosphamide. Instead, the patient underwent a LINX® procedure after failure of maximal medical therapy for gastroesophageal reflux disease with the additional aim of improving asthma control. After she underwent LINX® treatment, her asthma improved dramatically and was no longer refractory. She had normal exhaled nitric oxide levels and loss of peripheral eosinophilia after LINX® treatment. Prednisone was discontinued without loss of asthma control. The only immediate adverse effects due to the LINX® procedure were bloating, nausea, and vomiting. CONCLUSIONS: LINX® is a viable alternative to the Nissen fundoplication procedure for the treatment of patients with gastroesophageal reflux disease and poorly controlled concomitant refractory asthma.

Bronchial Artery Pseudoaneurysm With Major Hemorrhage After Bronchial Thermoplasty.

Bronchial thermoplasty has been found to be a safe and effective therapy for severe asthma. We report the case of a mediastinal hematoma and hemothorax developing in a 66-year-old woman several days after an uneventful bronchial thermoplasty of the right lower lobe. Evaluation revealed a bleeding right bronchial artery pseudoaneurysm. Pseudoaneuryms have been reported in association with other procedures involving the therapeutic application of thermal energy, and a single case of hemoptysis requiring bronchial artery embolization occurred in a clinical trial of bronchial thermoplasty. However, bronchial artery pseudoaneurysm with hemomediastinum and hemothorax has not previously been reported after bronchial thermoplasty.

Patient considerations in the treatment of COPD: focus on the new combination inhaler umeclidinium/vilanterol.

Medication adherence among patients with chronic diseases, such as COPD, may be suboptimal, and many factors contribute to this poor adherence. One major factor is the frequency of medication dosing. Once-daily dosing has been shown to be an important variable in medication adherence in chronic diseases, such as COPD. New inhalers that only require once-daily dosing are becoming more widely available. Combination once-daily inhalers that combine any two of the following three agents are now available: 1) a long-acting muscarinic antagonist; 2) a long acting beta2 agonist; and 3) an inhaled corticosteroid. A new once-daily inhaler with both a long-acting muscarinic antagonist, umeclidinium bromide, and a long acting beta2 agonist, vilanterol trifenatate, is now available worldwide for COPD treatment. It provides COPD patients convenience, efficacy, and a very favorable adverse-effects profile. Additional once-daily combination inhalers are available or will soon be available for COPD patients worldwide. The use of once-daily combination inhalers will likely become the standard maintenance management approach in the treatment of COPD because they improve medication adherence.