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What's new in pulmonary and critical care medicine

What's new in pulmonary and critical care medicine
Authors:
Helen Hollingsworth, MD
April F Eichler, MD, MPH
Geraldine Finlay, MD
Literature review current through: Feb 2022. | This topic last updated: Feb 28, 2022.

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

ASTHMA

Astegolimab and severe asthma (October 2021)

Interleukin (IL)-33 is released in response to irritants, viral infection, and allergens and acts on a broad array of cells via its receptor ST2. The investigational monoclonal antibody astegolimab interrupts IL-33/ST2 signaling and is proposed as a therapy for patients with severe asthma who do not respond to currently available biologic agents. A phase 2b multicenter randomized trial assigned 502 adults with poorly controlled severe asthma to one of three doses of astegolimab or placebo administered subcutaneously every four weeks for a year [1]. The highest dose of astegolimab reduced the annualized asthma exacerbation rate by more than 40 percent relative to placebo. Results in patients with blood eosinophils <300 cells/microL were similar to the overall group, supporting the hypothesis that IL-33 participates in asthma pathogenesis upstream from Th2 pathways. (See "Investigational agents for asthma", section on 'Anti-IL-33 and anti-IL-33/ST2 monoclonal antibodies'.)

COPD

Duration of IV antibiotics for acute pulmonary exacerbation of CF (November 2021)

The optimal duration of intravenous (IV) antibiotics in patients with cystic fibrosis (CF) is unknown. In a randomized study of adults with CF and an acute pulmonary exacerbation, 277 patients with early robust response were randomized to a 10- or 14-day course of antibiotics, and 705 slower responders were randomized to a 14- or 21-day course [2]. Within both groups, mean FEV1 change from baseline, improvements in symptoms score, rates of treatment failure, and drug-induced toxicity were similar regardless of the duration of antibiotics. These findings are likely applicable to children with CF and support our suggestion for a 10-day course of IV antibiotics for patients with an early robust response to therapy, and a 14-day course for those with a slower response to therapy. A longer course of antibiotics may be warranted for patients requiring intensive care and those who experience a CF exacerbation despite a recent course of IV antibiotics. (See "Cystic fibrosis: Treatment of acute pulmonary exacerbations", section on 'Duration of treatment'.)

Triple- versus dual- or mono-therapy with CFTR modulators for cystic fibrosis (September 2021)

Elexacaftor-tezacaftor-ivacaftor (triple cystic fibrosis transmembrane modulator [CFTR]) therapy is indicated for patients who are F508del homo- or heterozygotes. Individuals who are F508del heterozygotes may already be receiving tezacaftor-ivacaftor (dual therapy) or ivacaftor (monotherapy); the benefit of triple CFTR therapy in these patients is unclear. In a trial of more than 250 children (F508del heterozygotes ≥12 years of age), triple therapy for eight weeks improved respiratory symptoms, pulmonary function, and sweat chloride compared with active controls receiving either dual therapy (patients with F508del-residual function genotypes) or monotherapy (patients with F508del-gating genotypes) [3]. We suggest triple CFTR modulator therapy rather than dual or monotherapy for CF patients with genotypes that make them eligible for either one of these treatments. (See "Cystic fibrosis: Treatment with CFTR modulators", section on 'Efficacy'.)

CRITICAL CARE

Prolonged duration of symptoms in COVID-19 ICU survivors (February 2022)

The duration of symptoms following COVID-19 is unclear. A recent study reported that three-quarters of intensive care unit COVID-19 survivors had physical symptoms at one year. These included physical weakness (39 percent), joint symptoms (26 percent), and myalgia (21 percent) [4]. Mental symptoms were reported by 26 percent and cognitive symptoms by 16 percent of survivors. These symptoms are consistent with post-intensive care syndrome (PICS) and need to be addressed during recovery from COVID-19. (See "COVID-19: Evaluation and management of adults following acute viral illness", section on 'Persistent symptoms'.)

Three-step program of caregiver support for the dying patient (February 2022)

The optimal approach to support caregivers of dying patients in the intensive care unit (ICU) is unknown. One study described a successful approach with a three-step, physician-driven, nurse-aided support strategy for 875 relatives of patients dying in the ICU [5]. The first step was an end-of-life conversation, the second was a physical presence of health care personnel in the room during the dying process, and the third was a meeting to express condolences after death. Compared with standard care, at six months, the three-step program reduced the number of relatives with prolonged grief (PG) symptoms (21 versus 15 percent) and the median prolonged grief-13 questionnaire score (19 versus 21). This study supports the practice of a structured system designed to improve communication and empathy to caregivers of the dying in the ICU but may not be generalizable. (See "Withholding and withdrawing ventilatory support in adults in the intensive care unit".)

Target temperature after sudden cardiac arrest in adults (December 2021)

For patients who survive sudden cardiac arrest (SCA) and have an indication for targeted temperature management (TTM), the optimal temperature is unknown. Two studies have recently addressed this issue:

In a network meta-analysis of 10 randomized trials (over 4200 patients) survival with good function was similar for patients regardless of targeted temperature after SCA, including deep hypothermia (31 to 32°C), moderate hypothermia (33 to 34°C), mild hypothermia (35 to 36°C), or normothermia (37 to 37.8°C) [6]. However, moderate and deep hypothermia were associated with a higher incidence of arrhythmia when compared with normothermia (OR 1.45, and OR 3.58, respectively).

In a randomized trial of over 700 patients, not included in the above meta-analysis, no survival benefit or difference in neurologic outcomes was reported when a temperature of either 31°C (deep hypothermia) or 34°C (moderate hypothermia) was targeted for 24 hours after SCA [7]. There were no differences among the groups for adverse events except for a higher rate of deep vein thrombosis in those receiving deep hypothermia (4 versus 8 percent). However, the study may have been underpowered to detect a difference between the groups.

These trials suggest that deep hypothermia may not be beneficial for patients with SCA, although patients with severe neurologic injury were excluded from these and other trials. Until data support select target temperatures for specific subgroups, we advise individualizing targets for patients with SCA between the range of 33 and 37.5°C. (See "Intensive care unit management of the intubated post-cardiac arrest adult patient", section on 'Setting the target temperature'.)

Updated difficult airway guidelines for adults and children (December 2021)

The American Society of Anesthesiologists has updated its difficult airway guidelines for both adult and pediatric patients and created new algorithms (algorithm 1 and algorithm 2) and infographics. The new guidelines stress prioritizing oxygenation throughout airway management; confirming ventilation with end tidal CO2 regardless of the airway device used; and limiting attempts with each device or technique to three, with one more attempt by a more experienced operator [8]. The new guidelines also provide robust guidance for extubation. (See "Management of the difficult airway for general anesthesia in adults", section on 'Importance of an algorithmic approach'.)

Updated Surviving Sepsis Campaign guidelines (November 2021)

Recent adult guidelines were issued by the Surviving Sepsis Campaign [9]. Major changes with the 2016 guidelines included a preference for balanced salt solutions as the initial resuscitation fluid, a recommendation to not delay vasopressors while waiting for central venous access, and the administration of intravenous hydrocortisone to patients with ongoing septic shock. Additional changes included a recommendation against the administration of vitamin C as well as support for the early identification and treatment of mental, emotional, and physical ailments in survivors of sepsis. (See "Evaluation and management of suspected sepsis and septic shock in adults".)

Lower than usual tidal volumes and extracorporeal carbon dioxide removal for acute hypoxemic respiratory failure (October 2021)

Using a low tidal volume ventilation (LTVV) strategy for mechanically ventilated patients with acute respiratory distress syndrome (ARDS) is of proven survival benefit. Whether additional benefit can be achieved with even lower than usual tidal volumes (target <3 mL/kg of ideal body weight [IBW]) in conjunction with extracorporeal carbon dioxide (ECCO2) removal was recently studied in a randomized trial of 412 patients with acute hypoxemic respiratory failure, two-thirds of whom had ARDS [10]. Despite achieving lower tidal volumes, this strategy did not impact 90-day mortality (42 versus 40 percent) and actually resulted in fewer ventilator-free days (7.1 versus 9.2 days) and an increased rate of adverse events, most of which were due to ECCO2 (31 versus 9 percent). The trial was stopped early for futility. For patients with ARDS, we continue to support LTVV at 4 to 8 mL/kg IBW. (See "Ventilator management strategies for adults with acute respiratory distress syndrome", section on 'Ventilator strategies of questionable benefit or harm'.)

Use of TEE for perioperative management of ECMO (October 2021)

Echocardiography is a valuable diagnostic and monitoring tool often used before and during extracorporeal membrane oxygenation (ECMO) support, but few guidelines are available to help cardiac anesthesiologists who are frequently facilitating ECMO insertion and management. Now, the Society of Cardiovascular Anesthesiologists has published two consensus statements that include guidance regarding the role of transesophageal echocardiography (TEE) in performing patient assessments before initiating ECMO, facilitating insertion and final positioning of ECMO cannulae, monitoring and troubleshooting during ECMO support, and managing the weaning process [11,12]. We employ TEE guidance during perioperative management of ECMO. (See "The role of TEE in the management of extracorporeal membrane oxygenation", section on 'Uses of echocardiography for extracorporeal membrane oxygenation'.)

Plasma not helpful for mildly elevated INR (October 2021)

A new trial has documented the lack of benefit from using plasma to "correct" an increased prothrombin time (PT) and international normalized ratio (INR). The trial randomly assigned 57 hospitalized adults with an INR of 1.5 to 2.5 (approximately 60 percent with cirrhosis) who were undergoing a procedure outside the operating room to receive or not receive plasma [13]. There was little to no difference in post-procedure hemoglobin (a measure of bleeding), hospital length of stay, or adverse events. Although small, this trial adds further evidence that plasma should not be used to treat a mildly elevated INR. Appropriate uses of plasma include massive transfusion protocols, therapeutic plasma exchange, and treatment of bleeding due to one or more deficient clotting factors when a specific factor concentrate is unavailable. (See "Clinical use of plasma components", section on 'Settings in which plasma is not appropriate'.)

Fluid resuscitation with saline or a buffered crystalloid in adults (September 2021)

The choice between normal saline and a buffered crystalloid for initial fluid resuscitation in adults is debated. A recent two-by-two-factorial randomized trial of >11,000 critically ill patients (mostly surgical) treated with normal saline or a buffered crystalloid found that neither the fluid type nor the rate of administration had an impact on 90-day mortality or the incidence of acute kidney injury (AKI) [14,15]. However, the trial may have been underpowered, only small volumes of fluids were administered, and fluid was administered prior to randomization, all of which decrease confidence in the results. We suggest that the choice between fluids be individualized and re-evaluated following initial resuscitation. (See "Treatment of severe hypovolemia or hypovolemic shock in adults", section on 'Choosing between 0.9 percent saline and buffered crystalloid'.)

Awake proning in hospitalized patients with COVID-19 (September 2021)

Self-pronation has been a widespread practice for awake patients hospitalized with hypoxemic respiratory failure due to COVID-19 based on limited data indicating temporary improvements in oxygenation. In a recent meta-analysis of six randomized trials, awake pronation also reduced the rate of intubation in such patients (33 versus 40 percent), although a mortality benefit was not identified [16]. Given the minimal harms of self-proning, these data further support our recommendation for routine proning in awake patients with COVD-19-related respiratory failure. (See "COVID-19: Respiratory care of the nonintubated hypoxemic adult (supplemental oxygen, noninvasive ventilation, and intubation)", section on 'Awake pronation'.)

INTERSTITIAL LUNG DISEASE

Screening females with tuberous sclerosis for lymphangioleiomyomatosis (October 2021)

Adult females with tuberous sclerosis complex (TSC) have a high prevalence of lymphangioleiomyomatosis (LAM), a progressive cystic lung disorder that affects approximately 25 percent of patients at age 18 years and 80 percent at age 40 years. Based on this high prevalence, recent guidelines from the International TSC Consensus Guidelines group suggest screening asymptomatic females with TSC who were 18 years and older using low-dose noncontrast chest computed tomography (CT) [17]. If the CT does not reveal LAM cysts, it is repeated every 5 to 10 years. This guidance supports our current screening practices. (See "Tuberous sclerosis complex associated lymphangioleiomyomatosis in adults", section on 'Screening for TSC-LAM'.)

LUNG TRANSPLANTATION

ISHLT guidelines for lung transplant recipient selection (November 2021)

The International Society for Heart and Lung Transplantation (ISHLT) has updated their guidelines for selection of lung transplant recipients [18]. Careful donor selection is essential to optimize post-transplant results. Early referral for transplant evaluation is encouraged to allow time for a methodical evaluation and to address modifiable barriers to transplant. Clinical advances in transplantation mean that there are fewer absolute contraindications to lung transplant candidacy than prior guidelines. Risk factors that no longer represent absolute contraindications include BMI ≥35 kg/m2 and chest wall/spinal deformities; other contraindications (eg, malignancy, other vital organ dysfunction) are more precisely defined; and the relative contraindication of age >65 years has increased to >70 years. The new guidelines also update features that confer high risk of a poor outcome that may be manageable at selected centers and other factors that are unfavorable but may be acceptable when present in isolation. (See "Lung transplantation: General guidelines for recipient selection", section on 'Contraindications and risk factors for poor outcomes'.)

Testing potential lung donors for SARS-CoV-2 (September 2021)

Transmission of SARS-CoV-2 via a lung allograft has been reported from donors who initially tested negative by nasal swab but were later confirmed positive on a lower respiratory tract sample [19,20]. In response, the Organ Procurement and Transplantation Network (OPTN) has mandated that all potential lung donors undergo testing of a lower respiratory tract specimen (eg, tracheal aspirate, bronchoscopic washing, or bronchoalveolar lavage) for SARS-CoV-2 by nucleic acid test [21]. (See "Lung transplantation: Deceased donor evaluation", section on 'Pandemic coronavirus disease 2019 (COVID-19)'.)

PULMONARY VASCULAR DISEASE

Updated guidelines on venous thromboembolism management (January 2022)

Updated guidelines on the treatment of venous thromboembolism (VTE) were published by the American College of Chest Physicians (CHEST) [22]. Many recommendations are similar to those in the 2016 guideline but either expanded in scope or changed in strength of the recommendation. As new recommendations, for most patients with cancer-related VTE, CHEST suggests a direct oral anticoagulant (DOAC) rather than low molecular weight heparin. For select patients without cancer who require extended anticoagulation beyond the conventional period of three to six months, CHEST suggests low-intensity anticoagulation with a DOAC. While CHEST did not promote aspirin for VTE prevention, they suggest that it may reduce the risk of recurrence when compared with no therapy. (See "Overview of the treatment of lower extremity deep vein thrombosis (DVT)" and "Anticoagulation therapy for venous thromboembolism (lower extremity venous thrombosis and pulmonary embolism) in adult patients with malignancy" and "Selecting adult patients with lower extremity deep venous thrombosis and pulmonary embolism for indefinite anticoagulation".)

Comparison of protocols for the diagnosis of pulmonary embolism (January 2022)

The ideal strategy for diagnosing pulmonary embolism (PE) is unknown. One meta-analysis reported that protocols that used pretest probability (PTP) models, adjusted D-Dimer levels, and/or YEARs criteria excluded more cases of PE without imaging (high efficiency) [23]. However, they also had the highest failure rate (ie, more missed cases of VTE). In addition, such protocols did not perform uniformly across all subgroups, with the lowest efficiency observed in those who were 80 years of age or older and in patients with cancer. In patients with suspected PE, we prefer to use a conventional protocol that combines clinical PTP and unadjusted D-Dimer to direct imaging. Although this approach is associated with a higher rate of imaging, fewer cases of PE are missed and we value the role of imaging when looking for alternate causes of patients' symptoms. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Adjusted D-dimer'.)

Recurrence rates in subsegmental pulmonary embolism (December 2021)

In patients with subsegmental pulmonary embolism (SSPE), the incidence of venous thromboembolism (VTE) recurrence is unclear. Older retrospective studies suggested low recurrence rates [24-26]. A more recent and larger prospective study of 292 patients with SSPE and no evidence of deep venous thrombosis (DVT) who were managed without anticoagulation reported a recurrence rate of 3.1 percent at 90 days, which is higher than the expected rate in the general population (<1 percent) [27]. Rates were highest in those with multiple SSPE (5.7 percent) and older patients >65 years (5.5 percent). No fatalities were reported. This study supports our practice of routine anticoagulation for most patients with SSPE. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Patients with subsegmental PE'.)

YEARS plus age-adjusted D-Dimer to diagnose PE (December 2021)

In a recent randomized trial of over 1200 patients who were positive for pulmonary embolism (PE) rule out criteria (PERC) (table 1) and had a low or intermediate clinical probability of PE, further triage using YEARS criteria plus age-adjusted D-Dimer (intervention group) resulted in a 10 percent reduction in chest imaging and a 1.6-hour reduction in the emergency department (ED) stay without significantly impacting the three-month rate of venous thromboembolism (VTE) compared with age-adjusted D-Dimer alone (conventional group) [28]. While encouraging, the complexity of this protocol may not be practical in busy settings. We continue to use a simple protocol that uses the more conventional strategy of clinical pretest probability and unadjusted D-Dimer. Although this strategy leads to more imaging, we place value in chest imaging which can help explain patients' symptoms when PE is not found. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Adjusted D-dimer'.)

Choosing apixaban or rivaroxaban for venous thromboembolism (December 2021)

Although several direct oral anticoagulants (DOACs) are available for treating patients with venous thromboembolism (VTE), no randomized trials support choosing one over another. A recent retrospective study reported that among 37,000 new users of apixaban or rivaroxaban, apixaban was associated with lower rates of recurrent VTE (hazard ratio [HR] 0.77, 95% CI 0.69-0.87) and bleeding (HR 0.60, 95% CI 0.53-0.69) [29]. While these data favor apixaban, we continue to favor an individualized choice among DOACs that also take into consideration cost, availability, and preference for once- versus twice-daily dosing. (See "Venous thromboembolism: Anticoagulation after initial management", section on 'Efficacy' and "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects".)

Long-term bleeding rates with direct oral anticoagulants (September 2021)

For patients with unprovoked venous thromboembolism (VTE), accurate information about bleeding rates are needed to inform decision-making. A recent meta-analysis of 27 studies (including 14 randomized trials) and >17,000 adults with unprovoked VTE reported a lower rate of bleeding among those receiving direct oral anticoagulants (DOACs) compared with patients receiving warfarin (1.12 versus 1.74 events per 100 person-years) [30]. Rates of bleeding were highest among patients >65 years of age and those with a creatinine clearance <50 mL/min, a history of bleeding, concomitant use of antiplatelet therapy, or a hemoglobin level <10 mg/L. These findings support our suggested choice of a DOAC rather than warfarin for most patients in whom indefinite anticoagulant therapy is indicated. (See "Selecting adult patients with lower extremity deep venous thrombosis and pulmonary embolism for indefinite anticoagulation", section on 'Baseline risk'.)

LMW heparin dosing in individuals with high BMI (September 2021)

Optimal dosing of low molecular weight (LMW) heparins for individuals with high body mass index (BMI) is unknown, and guideline recommendations are variable regarding whether to prefer fixed dosing or weight-based dosing for venous thromboembolism (VTE) prophylaxis. A new meta-analysis has evaluated data from 11 studies (nearly 20,000 medical and surgical patients with high BMI) treated with fixed-dose or weight-based dose LMW heparin and found little or no difference in the rates of recurrent VTE or bleeding [31]. Although more data are needed, these results are reassuring and suggest that both approaches are reasonable. (See "Heparin and LMW heparin: Dosing and adverse effects", section on 'Dosing at extremes of body weight'.)

Direct oral anticoagulants for venous thromboembolism in children ≥2 years (August 2021)

In 2021, the US Food and Drug Administration approved two direct oral anticoagulants (DOACs), dabigatran and rivaroxaban, for treatment of venous thrombosis and thromboembolism (VTE) in children [32,33]. These regulatory approvals were based upon two large multicenter pediatric trials demonstrating that dabigatran and rivaroxaban have similar efficacy and bleeding risk compared with low molecular weight heparin (LMWH) and warfarin [34,35]. Adolescents made up most of the trial populations, and children <2 years were underrepresented. DOACs are an attractive option since they are orally administered and do not require drug monitoring. We now suggest one of the approved DOACs (dabigatran or rivaroxaban) for treatment of VTE in adolescents, after at least five days of initial parenteral therapy. For children ages 2 to 11 years, either a DOAC or LMWH is acceptable. For infants and children <2 years, the efficacy and safety of DOACs remain uncertain, and we continue to suggest LMWH. (See "Venous thrombosis and thromboembolism (VTE) in children: Treatment, prevention, and outcome", section on 'Direct oral anticoagulants'.)

SLEEP MEDICINE

Effects of rotating work shift direction on sleep and performance (November 2021)

Sleep duration and sleep quality are commonly affected in shift workers, and certain patterns of shift rotation may be more difficult than others. In a cohort study of 144 nurses working shifts that were either forward-rotating (ie, morning, then afternoon, then overnight) or backward-rotating, both schedules were associated with adverse performance, but levels of sleepiness and decrements in vigilance and reaction time were greater among those on a backward-rotating schedule [36]. These data confirm previous impressions that individuals may find it easier to adjust to forward-rotating shift schedules, particularly if the speed of rotation is slow (eg, >4 days per shift assignment). (See "Sleep-wake disturbances in shift workers", section on 'Sleep disturbances'.)

Nonbenzodiazepine sedatives and adherence to CPAP (September 2021)

Nonadherence to continuous positive airway pressure (CPAP) therapy for patients with obstructive sleep apnea (OSA) is common. Whether sedatives should be used to encourage adherence was the subject of a recent meta-analysis of eight studies in >1000 patients with OSA [37]. Patients who were treated with nonbenzodiazepine sedatives had higher rates of adherence than those who did not receive sedatives (eg, 0.6 hour greater use per night, 12 percent increase in number of nights used). However, results were heavily influenced by trials that used one drug, eszopiclone, and data are conflicting. We do not suggest routine use of a sedative-hypnotic at the time of CPAP initiation and reserve this approach for patients who fail other interventions to address adherence. (See "Assessing and managing nonadherence with continuous positive airway pressure (CPAP) for adults with obstructive sleep apnea", section on 'Pharmacological therapy'.)

OTHER PULMONARY MEDICINE

CDC definition of post-acute COVID-19 (October 2021)

The Centers for Disease Control and Prevention (CDC) recently updated their definition of post-acute sequelae of SARS-CoV-2 infection (PASC; "long-COVID") [38]. While it was previously defined as "patients with a broad range of symptoms (physical and mental) that develop during or after COVID-19, continue for ≥4 weeks, and are not explained by an alternate diagnosis," the CDC further specified the duration of symptoms to include only those with symptoms for ≥2 months (ie, 3 months from the onset). (See "COVID-19: Evaluation and management of adults following acute viral illness", section on 'Terminology and stages of recovery'.)

Post-COVID-19 symptoms not affected by vaccination (October 2021)

Some patients with persistent symptoms following COVID-19 are concerned that vaccination could exacerbate them. A recent study of 163 patients who had a heavy burden of post-COVID-19 symptoms at eight months reported that most patients' symptoms had either improved or remained unchanged one month after receiving either the BNT162b2 (Pfizer) or ChAdOx1 nCoV-19/AZD1222 (AstraZeneca) vaccine [39]. We continue to recommend vaccination in patients following COVID-19, regardless of the presence of persistent symptoms. (See "COVID-19: Vaccines", section on 'History of SARS-CoV-2 infection' and "COVID-19: Evaluation and management of adults following acute viral illness", section on 'Persistent symptoms'.)

Risk of GI bleeding with DOACs (October 2021)

Direct oral anticoagulants (DOACs) are generally preferred over warfarin in individuals with non-valvular atrial fibrillation or venous thromboembolism. A new study evaluated the risk of gastrointestinal (GI) bleeding in over 5000 individuals taking apixaban, rivaroxaban, or dabigatran [40]. Higher rates of GI bleeding were seen in individuals taking rivaroxaban (3.2 per 100 patient-years) than with the other agents (2.5 for apixaban and 1.9 for dabigatran). The once-daily dosing of rivaroxaban and higher peak levels may explain the higher bleeding risk; the other agents are dosed twice daily. These results may be a consideration when choosing among DOACs. (See "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects", section on 'Differences between factor Xa inhibitors'.)

New antineutrophil cytoplasmic antibody-associated vasculitis guideline (September 2021)

The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides are a group of diseases that involve inflammation of small and medium-sized vessels and include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). The American College of Rheumatology (ACR)/Vasculitis Foundation has recently published guidelines for the management of the ANCA-associated vasculitides [41]. These guidelines provide recommendations for induction and maintenance therapy for GPA, MPA, and EGPA, which are largely consistent with our approach. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy", section on 'Initial treatment approach'.)

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  28. Freund Y, Chauvin A, Jimenez S, et al. Effect of a Diagnostic Strategy Using an Elevated and Age-Adjusted D-Dimer Threshold on Thromboembolic Events in Emergency Department Patients With Suspected Pulmonary Embolism: A Randomized Clinical Trial. JAMA 2021; 326:2141.
  29. Dawwas GK, Leonard CE, Lewis JD, Cuker A. Risk for Recurrent Venous Thromboembolism and Bleeding With Apixaban Compared With Rivaroxaban: An Analysis of Real-World Data. Ann Intern Med 2022; 175:20.
  30. Khan F, Tritschler T, Kimpton M, et al. Long-Term Risk for Major Bleeding During Extended Oral Anticoagulant Therapy for First Unprovoked Venous Thromboembolism : A Systematic Review and Meta-analysis. Ann Intern Med 2021; 174:1420.
  31. Ceccato D, Di Vincenzo A, Pagano C, et al. Weight-adjusted versus fixed dose heparin thromboprophylaxis in hospitalized obese patients: A systematic review and meta-analysis. Eur J Intern Med 2021; 88:73.
  32. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-blood-thinning-medication-children (Accessed on June 25, 2021).
  33. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-drug-treat-help-prevent-types-blood-clots-certain-pediatric-populations (Accessed on January 14, 2022).
  34. Halton J, Brandão LR, Luciani M, et al. Dabigatran etexilate for the treatment of acute venous thromboembolism in children (DIVERSITY): a randomised, controlled, open-label, phase 2b/3, non-inferiority trial. Lancet Haematol 2021; 8:e22.
  35. Male C, Lensing AWA, Palumbo JS, et al. Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial. Lancet Haematol 2020; 7:e18.
  36. Di Muzio M, Diella G, Di Simone E, et al. Comparison of Sleep and Attention Metrics Among Nurses Working Shifts on a Forward- vs Backward-Rotating Schedule. JAMA Netw Open 2021; 4:e2129906.
  37. Wang D, Tang Y, Chen Y, et al. The effect of non-benzodiazepine sedative hypnotics on CPAP adherence in patients with OSA: a systematic review and meta-analysis. Sleep 2021; 44.
  38. World Health Organization. A clinical case definition of post-COVID-19 condition by a Delphi consensus, 6 October 2021. https://www.who.int/publications/i/item/WHO-2019-nCoV-Post_COVID-19_condition-Clinical_case_definition-2021.1 (Accessed on October 11, 2021).
  39. Arnold DT, Milne A, Samms E, et al. Symptoms After COVID-19 Vaccination in Patients With Persistent Symptoms After Acute Infection: A Case Series. Ann Intern Med 2021; 174:1334.
  40. Ingason AB, Hreinsson JP, Ágústsson AS, et al. Rivaroxaban Is Associated With Higher Rates of Gastrointestinal Bleeding Than Other Direct Oral Anticoagulants : A Nationwide Propensity Score-Weighted Study. Ann Intern Med 2021; 174:1493.
  41. Chung SA, Langford CA, Maz M, et al. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Arthritis Care Res (Hoboken) 2021; 73:1088.
Topic 8355 Version 10977.0

References

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4 : Clinical Outcomes Among Patients With 1-Year Survival Following Intensive Care Unit Treatment for COVID-19.

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26 : Risk profile and clinical outcome of symptomatic subsegmental acute pulmonary embolism.

27 : Risk for Recurrent Venous Thromboembolism in Patients With Subsegmental Pulmonary Embolism Managed Without Anticoagulation : A Multicenter Prospective Cohort Study.

28 : Effect of a Diagnostic Strategy Using an Elevated and Age-Adjusted D-Dimer Threshold on Thromboembolic Events in Emergency Department Patients With Suspected Pulmonary Embolism: A Randomized Clinical Trial.

29 : Risk for Recurrent Venous Thromboembolism and Bleeding With Apixaban Compared With Rivaroxaban: An Analysis of Real-World Data.

30 : Long-Term Risk for Major Bleeding During Extended Oral Anticoagulant Therapy for First Unprovoked Venous Thromboembolism : A Systematic Review and Meta-analysis.

31 : Weight-adjusted versus fixed dose heparin thromboprophylaxis in hospitalized obese patients: A systematic review and meta-analysis.

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33 : Weight-adjusted versus fixed dose heparin thromboprophylaxis in hospitalized obese patients: A systematic review and meta-analysis.

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35 : Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial.

36 : Comparison of Sleep and Attention Metrics Among Nurses Working Shifts on a Forward- vs Backward-Rotating Schedule.

37 : The effect of non-benzodiazepine sedative hypnotics on CPAP adherence in patients with OSA: a systematic review and meta-analysis.

38 : The effect of non-benzodiazepine sedative hypnotics on CPAP adherence in patients with OSA: a systematic review and meta-analysis.

39 : Symptoms After COVID-19 Vaccination in Patients With Persistent Symptoms After Acute Infection: A Case Series.

40 : Rivaroxaban Is Associated With Higher Rates of Gastrointestinal Bleeding Than Other Direct Oral Anticoagulants : A Nationwide Propensity Score-Weighted Study.

41 : 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.