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What's new in pulmonary and critical care medicine

What's new in pulmonary and critical care medicine
Paul Dieffenbach, MD
April F Eichler, MD, MPH
Geraldine Finlay, MD
Literature review current through: Nov 2022. | This topic last updated: Dec 19, 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.


Persistence of asthma control after stopping omalizumab therapy (November 2022)

Omalizumab, an anti-IgE monoclonal antibody, is an effective add-on therapy for uncontrolled moderate-to-severe asthma but the optimal duration of therapy and the persistence of benefit after discontinuation are unclear. In an analysis of the French national healthcare database that included over 19,000 patients with asthma (over 2000 children) who received omalizumab for a median duration of approximately 4.5 years, rates of asthma hospitalizations were reduced by 75 percent and the need for oral corticosteroids by 30 percent after two years of treatment [1]. Among patients with asthma control during treatment, symptoms remained controlled in a significant percentage one, two, and three years after discontinuation (76, 44, and 33 percent in children and 70, 39, and 24 percent in adults, respectively). These findings indicate a lasting benefit after discontinuation of omalizumab in patients with controlled asthma and provide a basis for anticipatory guidance for those who discontinue treatment. (See "Anti-IgE therapy", section on 'Observations post-treatment'.)

Insulin resistance in severe asthma (November 2022)

Several studies have identified an increased prevalence of asthma and difficult-to-control asthma among obese individuals, although the exact reason for the association is not known. A recent study of patients with severe asthma included extensive metabolic phenotyping as well as long-term follow-up [2]. Patients with insulin resistance demonstrated more rapid decline in lung function and increased resistance to beta-agonist and oral glucocorticoid therapies compared with patients having normal insulin sensitivity. Whether targeting insulin resistance can impact these severe asthma features requires further investigation. (See "Severe asthma phenotypes", section on 'Asthma associated with obesity'.)

Mepolizumab for childhood asthma in urban under-served populations (October 2022)

Among adults and adolescents with severe eosinophilic asthma, treatment with mepolizumab (a monoclonal antibody to interleukin-5) reduces exacerbation rates; however, data in children are limited. Mepolizumab was compared with placebo in a trial of children and adolescents recruited from low-income, primarily urban environments in the United States who presented with poorly controlled asthma and elevated blood eosinophils. Mepolizumab reduced asthma exacerbation rates compared with placebo in this population (1.0 versus 1.3 per year, relative risk 0.73), but the improvement was less than that observed in prior trials of adults and adolescents (relative risk approximately 0.50) [3]. Whether this lesser performance is due to ongoing environmental exposure, higher levels of noneosinophilic inflammation, biologic changes between childhood and adult asthma, or other differences in the overall study populations is not well understood. (See "Treatment of severe asthma in adolescents and adults", section on 'Mepolizumab'.)

Risk factors for thunderstorm asthma (July 2022)

"Thunderstorm asthma" refers to asthma exacerbations that occur in the hours after a thunderstorm, especially storms occurring during pollen seasons. The mechanism appears to involve rupture of water-logged pollen grains, which releases allergenic debris that is swept up by strong cross currents and deposited in concentrated form at ground level. In a multicenter study of adults with a past diagnosis of thunderstorm asthma and/or seasonal allergic rhinitis, risk factors for thunderstorm asthma included higher pollen-specific immunoglobulin E levels, eosinophil counts, and fractional exhaled nitric oxide levels as well as asthma that was not optimally controlled [4]. Clinicians and patients should be aware that thunderstorms can precipitate asthma and patients with pollen allergies and asthma should avoid the outdoors during and after thunderstorms occurring during pollen seasons. (See "Trigger control to enhance asthma management", section on 'Thunderstorms'.)

Asthma designation as a risk factor for COVID-19 (June 2022)

The United States Centers for Disease Control and Prevention (CDC) have recently identified asthma as a risk factor for severe COVID-19 [5]. Several studies including patients with well-controlled asthma do not indicate increased risk in this population; however, some data suggest higher rates of intubation and prolonged mechanical ventilation among all adults with asthma. These complications likely occur more frequently in those with poorly controlled asthma at baseline. Based on the CDC designation, patients with asthma may be prioritized for antiviral therapies if they develop COVID-19. (See "An overview of asthma management", section on 'Advice related to COVID-19 pandemic'.)

Patient-activated reliever-triggered inhaled glucocorticoid strategy (PARTICS) (May 2022)

A patient-activated reliever-triggered inhaled glucocorticoid strategy (PARTICS) involves the use of inhaled glucocorticoids in addition to beta-2 agonists whenever rescue medication is used. Two recent trials in patients with poorly controlled moderate-severe asthma found that PARTICS reduced the annualized rate of severe exacerbations by approximately 0.15 compared with usual care [6,7]. Practically, this strategy currently requires patients to carry multiple rescue inhalers, which may be unattractive to many patients. Nevertheless, PARTICS adds to growing evidence for increased effectiveness of inhaled glucocorticoids in addition to rescue therapy in preventing asthma exacerbations and may be a useful alternative reliever regimen. (See "Treatment of moderate persistent asthma in adolescents and adults", section on 'Patient-activated reliever-triggered inhaled corticosteroid strategy (PARTICS)'.)


Oral antihyperglycemic agents and prevention of COPD exacerbations (November 2022)

Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium-glucose co-transporter 2 (SGLT-2) inhibitors are antihyperglycemics increasingly used for the treatment of type 2 diabetes not controlled by metformin. In a recent study of patients with chronic obstructive pulmonary disease (COPD) and new initiation of an antihyperglycemic agent, patients who began GLP-1 receptor agonists or SGLT-2 inhibitors were less likely to be hospitalized for COPD exacerbations than similar patients receiving sulfonylureas, through as yet undefined mechanisms [8]. Future trials are needed to determine whether use of GLP-1 receptor agonists or SGLT-2 inhibitors are preferable to other antihyperglycemic agents in patients with diabetes mellitus and risk for COPD exacerbations. (See "COPD exacerbations: Prognosis, discharge planning, and prevention", section on 'GLP-1 receptor agonists and SGLT-2 inhibitors, for diabetic patients'.)

Bronchodilators in tobacco-exposed persons with symptoms and preserved lung function (September 2022)

Epidemiologic studies suggest that nearly 50 percent of current and former smokers have respiratory symptoms but do not have evidence of airway obstruction on pulmonary function testing. While many of these patients are treated off-label with bronchodilators or inhaled glucocorticoids, a recent trial failed to show improvement in respiratory symptoms or quality of life with dual long-acting bronchodilator therapy (indacaterol-glycopyrrolate) versus placebo in this population [9]. Based on these data, we do not offer bronchodilator treatment in symptomatic current or former smokers without airway obstruction. (See "Chronic obstructive pulmonary disease: Definition, clinical manifestations, diagnosis, and staging", section on 'Symptoms and pattern of onset'.)

Intravenous magnesium in severe COPD exacerbation (August 2022)

Intravenous magnesium has short-acting bronchodilator activity that is helpful for severe asthma attacks, but it has not previously been recommended for chronic obstructive pulmonary disease (COPD). A new systematic review and meta-analysis found a decrease in hospitalization rates with emergency department intravenous magnesium administration compared with placebo [10]. The effect size is similar to or better than that seen in the setting of asthma exacerbation. Based on these data, we now suggest intravenous magnesium for patients with severe COPD exacerbations who are not improving with inhaled bronchodilator therapy. (See "COPD exacerbations: Management", section on 'Magnesium sulfate'.)

Underdiagnosis of emphysema using race-based spirometric reference equations (July 2022)

The incorporation of race/ethnicity into reference equations for spirometry and other lung function tests is controversial. In one cohort study, the use of race-neutral equations increased the number of Black participants correctly diagnosed with emphysema by spirometry, such that racial differences in undiagnosed emphysema between White and Black participants were greatly attenuated [11]. These data suggest that one unintended consequence of race/ethnicity-specific equations is underdiagnosis of pulmonary disease in Black populations. Although it is reasonable to continue use of current reference equations for lung function testing until universal normative values have been well established, clinicians should be mindful of this evidence when interpreting results. Use of the "Global Lung Function Initiative (GLI)-other" spirometry reference equation for all races/ethnicities is another reasonable option. (See "Selecting reference values for pulmonary function tests", section on 'Effect of race/ethnicity'.)

Fazirsiran for liver disease due to severe alpha-1 antitrypsin deficiency (July 2022)

Adults with severe alpha-1 antitrypsin (AAT) deficiency are at risk for liver injury, but the only available treatments are supportive cirrhosis care and liver transplantation. Fazirsiran, an investigational inhibitory RNA (RNAi) agent designed to prevent toxic accumulation of AAT protein in the liver, was evaluated in 16 patients with PI*ZZ AAT deficiency [12]. Subcutaneous administration of fazirsiran led to decreased liver AAT levels, reduced portal inflammation, and, in nearly half the patients, regression of fibrosis at 24- or 48-week follow-up. Fazirsiran was well-tolerated without evidence of pulmonary function decline or chronic obstructive pulmonary disease exacerbations. Additional data are needed to establish the utility of this agent in clinical practice. (See "Extrapulmonary manifestations of alpha-1 antitrypsin deficiency", section on 'Management'.)


Haloperidol does not decrease mortality in mechanically ventilated patients with delirium (December 2022)

Haloperidol is frequently used to treat delirium in critically ill adults. A recent randomized trial of 1000 mechanically ventilated patients found that treatment of delirium with haloperidol did not alter the number of days alive outside the hospital at 90 days compared with placebo [13]. Limitations of the trial include a lack of data on other sedatives used and possible poor enrollment of patients with hypoactive delirium. These findings support prior studies that suggest that haloperidol can be safely used to treat delirium in ventilated patients but confers no mortality benefit. (See "Sedative-analgesic medications in critically ill adults: Properties, dose regimens, and adverse effects", section on 'Antipsychotics'.)

Prevalence of long COVID (December 2022)

The true prevalence of long COVID-19 is unknown due to varying definitions and methods of analysis. However, a meta-analysis of 54 studies estimated that 6.2 percent of individuals who had symptomatic COVID-19 infection between March 2020 and January 2022 experienced at least one long COVID symptom [14]. These data shed light on the true prevalence of long COVID-19. Whether this rate is also reflective of infection with the omicron variant requires additional study. (See "COVID-19: Evaluation and management of adults with persistent symptoms following acute illness ("Long COVID")", section on 'Prevalence'.)

Reduced ventilatory response to hypercapnia by opioid alternatives (December 2022)

Opioids are known to decrease the ventilatory response to hypercapnia. Whether other drugs commonly used in place of opioids can cause similar effects was studied in 19 healthy volunteers using carbon dioxide rebreathing technology [15]. Individuals were treated with oral quetiapine (100 mg to 400 mg twice daily), paroxetine (40 mg daily), or either drug combined with oxycodone (10 mg daily) and compared with oxycodone alone or placebo. Paroxetine alone and paroxetine combined with oxycodone decreased the ventilatory response to hypercapnia while quetiapine alone or combined with oxycodone did not cause such an effect. This study highlights potential harm associated with opioid alternatives but further study is needed to determine if this effect is clinically relevant and persistent in the long term. (See "Control of ventilation", section on 'Alterations in ventilatory response to CO2 and O2'.)

Aggressive early mobilization not of benefit in ventilated patients (December 2022)

Early mobilization within the first 72 hours in stable mechanically-ventilated patients is one strategy to decrease muscle weakness associated with post-intensive care unit syndrome and is supported by the American Thoracic Society, American College of Chest Physicians, and Society of Critical Care Medicine. In a recent, multicenter randomized trial of 750 ventilated patients, aggressive early mobilization (increased duration of sedation minimization and daily physiotherapy) did not impact the number of days alive outside of the hospital or three-month mortality when compared with conventional early mobilization strategies [16]. Moreover, it was associated with an increased rate of adverse events, mostly arrhythmia, oxygen desaturation, and altered blood pressure. These findings support current protocols rather than aggressive mobilization. (See "Post-intensive care syndrome (PICS)", section on 'Prevention'.)

No difference between pressure support and T-piece breathing trials in ventilated patients (December 2022)

In mechanically ventilated patients, spontaneous breathing trials (SBTs) are typically done to determine readiness for extubation, but the optimal method for performing SBTs is uncertain (ie, pressure support ventilation [PSV]- or T-piece SBTs). A recent multicenter trial of over 960 patients at high risk of extubation failure reported no difference in the number of ventilator-free days or rate of successful extubation or reintubation when PSV-SBT was compared with T-piece SBT [17]. However, most patients received prophylactic noninvasive ventilatory support immediately following extubation which may have minimized the difference between the groups. We continue to suggest PSV-SBT rather than T-piece SBT in patients at high risk of extubation failure, although the latter may be acceptable in select patients. (See "Initial weaning strategy in mechanically ventilated adults", section on 'Choosing ventilatory support'.)

Xylazine adulteration of illicit drugs (December 2022)

Xylazine is an alpha-2 agonist and a chemical analogue of clonidine that is used in veterinary medicine for sedation and analgesia. In humans, xylazine overdose has caused major toxicity consisting of coma, apnea, bradycardia, and hypotension as well as severe, necrotic skin ulcerations after repeated parenteral use. Xylazine is increasingly found as an adulterant in illicit drugs, especially heroin and fentanyl, with rising reports of serious side effects. As a result, the US Food and Drug Administration has issued an alert to health care professionals and a letter to stakeholders [18]. Xylazine poisoning is on the differential diagnosis for patients with suspected opioid overdose that does not respond to naloxone administration. Treatment consists of supportive care. There is no rapid diagnostic testing for xylazine poisoning or safe antidote. (See "Clonidine and related imidazoline poisoning", section on 'Imidazoline agents'.)

Blood pressure and oxygen targets following sudden cardiac arrest (September 2022)

Supporting data to guide specific blood pressure and oxygen targets after sudden cardiac arrest (SCA) are limited, and practice is variable. In a recent open-label, two-by-two factorial trial, 789 patients with SCA were randomly assigned to a high versus low mean arterial pressure (MAP) target (77 versus 63 mmHg) as well as a restrictive versus liberal arterial oxygen tension (PaO2) target (68 to 75 versus 98 to 105 mmHg) [19,20]. At 90 days, rates of death or severe disability/coma at discharge were similar across all groups. Although the trial had limitations and confidence intervals were wide, these results do not support aggressive MAP goals or overly restrictive oxygenation in the care of patients after cardiac arrest, pending future studies. (See "Intensive care unit management of the intubated post-cardiac arrest adult patient", section on 'Hemodynamic monitoring and goals'.)

Dexmedetomidine and delirium in critically ill patients (August 2022)

Data have been conflicting regarding clinical benefit associated with dexmedetomidine as a sedative in critically ill patients. A recent meta-analysis of 77 randomized trials (almost 12,000 patients) reported that compared with other sedatives, dexmedetomidine reduced the risk of delirium (relative risk 0.67, 95% CI 0.55-0.81; moderate certainty) but increased the risk of bradycardia and hypotension [21]. We agree with a recent guideline committee that dexmedetomidine can be successfully used as a sedative when the goal of reducing delirium is outweighed by the undesirable effects of hypotension and bradycardia [22]. (See "Sedative-analgesic medications in critically ill adults: Properties, dose regimens, and adverse effects", section on 'Efficacy'.)

De-escalation of fluid therapy in sepsis (June 2022)

In patients with sepsis, there is little guidance regarding when and how intravenous fluids (IVF) should be de-escalated following initial resuscitation. In a recent trial of over 1500 adults with sepsis who had received at least 1 liter of fluid and were within 12 hours of the onset of shock, individuals assigned to restrictive IVF strategy (ie, infusion stopped; small boluses given when needed for organ perfusion, low urine output, or insensible losses) compared with a standard IVF strategy had similar 90-day mortality and adverse effects [23]. These data support the safety of a restrictive approach to fluid de-escalation. However, the volume of fluid in both groups was lower than that previously reported in early resuscitation sepsis studies suggesting that practice has evolved toward a de-escalation approach that is restrictive. More studies are needed to further guide postresuscitation fluid therapy in patients with sepsis. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on 'De-escalation fluids'.)

Vitamin C alone not effective in sepsis (June 2022)

Early observational evidence suggested a possible mortality benefit from intravenous (IV) vitamin C in combination with thiamine and hydrocortisone in patients with sepsis. However, several randomized trials have since reported a lack of benefit from this combination. A recent trial of 872 patients with septic shock (and on a vasopressor) has reported that IV vitamin C alone also had no effect on 28-day mortality (35 versus 32 percent) or persistent organ dysfunction (9 versus 7 percent) [24]. One patient had severe hypoglycemia and another had anaphylaxis in response to vitamin C. We continue to recommend against the routine use of vitamin C alone or in combination with thiamine or hydrocortisone. (See "Investigational and ineffective therapies for sepsis", section on 'Vitamin C'.)

Routine preintubation fluid bolus does not prevent cardiovascular collapse in critically ill adults (June 2022)

Hypotension occurs in up to 50 percent of critically ill patients during and after intubation, and can cause cardiac arrest. If time permits, preintubation hemodynamic optimization is recommended, including correction of hypovolemia. However, in a randomized multicenter trial in >1000 critically ill adults, routine administration of a 500 mL intravenous (IV) fluid bolus prior to intubation did not reduce the incidence of cardiovascular collapse compared with no fluid bolus [25], consistent with a previous smaller trial. Methods to reduce peri-intubation hypotension should be individualized and may include use of etomidate or ketamine for induction, use of vasopressors, and IV fluid if necessary. (See "Complications of airway management in adults", section on 'Hemodynamic changes'.)


COVID-19 outcomes in lymphangioleiomyomatosis (August 2022)

The impact of COVID-19 on females with lymphangioleiomyomatosis (LAM) is unknown. In a recent observational study of 91 patients with LAM who had COVID-19, one-third required hospital admission, and the proportion requiring noninvasive or invasive mechanical ventilation was low (2 percent each) [26]. Mortality was no different than that in the general population, and the use of mechanistic target of rapamycin inhibitors was not associated with worse outcomes. These outcomes are favorable when compared with other chronic lung disease cohorts and might be partially explained by the young age of this population. (See "Sporadic lymphangioleiomyomatosis: Treatment and prognosis", section on 'COVID-19'.)

Risk of acute exacerbation of interstitial lung disease after COVID-19 vaccination or infection (August 2022)

Whether the COVID-19 mRNA vaccine affects idiopathic pulmonary fibrosis (IPF) remains unclear. In a new case series including four patients with IPF, COVID-19 mRNA vaccination was temporally associated with acute exacerbations of the underlying lung disease [27], consistent with previous case reports. However, earlier data and clinical experience suggest that infection with COVID-19 poses a greater risk than vaccination for those with IPF. Until further data are available, we continue to recommend COVID-19 vaccination for patients with interstitial lung disease. (See "Treatment of idiopathic pulmonary fibrosis", section on 'Prevention of pulmonary infections and acute exacerbations'.)

Phosphodiesterase 4B inhibitor therapy in idiopathic pulmonary fibrosis (July 2022)

Although antifibrotic therapy with pirfenidone or nintedanib can slow progression of idiopathic pulmonary fibrosis (IPF), phosphodiesterase 4B (PDE4B) inhibitors are a novel class of agent with both antifibrotic and immunomodulatory effects. In a randomized trial in 97 patients with IPF, the oral PDE4 inhibitor BI 1015550 prevented decline in forced vital capacity over 12 weeks compared with placebo [28]. The effect was smaller but still significant in patients on background antifibrotics. Thirteen patients (13 percent) discontinued the agent for toxicity, with the most common adverse effect being diarrhea. Additional evaluation of this inhibitor in phase III clinical trials is anticipated. (See "Treatment of idiopathic pulmonary fibrosis", section on 'Phosphodiesterase 4B inhibitor (BI 1015550)'.)

Empiric treatment of gastroesophageal reflux in idiopathic pulmonary fibrosis (July 2022)

Gastroesophageal reflux (GER) has been hypothesized to play a role in idiopathic pulmonary fibrosis (IPF) progression as a source of ongoing injury and inflammation in the lower lobes of the lung. An international practice guideline committee reviewed the limited available data on antireflux therapies for GER in patients with IPF and concluded that these therapies should not be used empirically to improve pulmonary outcomes [29]. UpToDate agrees with this approach, although more research is needed in this area. (See "Treatment of idiopathic pulmonary fibrosis", section on 'Empiric treatment for asymptomatic gastroesophageal reflux'.)


Dose of LMW heparin for VTE prevention in pregnancy (November 2022)

Low molecular weight (LMW) heparin is used for venous thromboembolism (VTE) prophylaxis during pregnancy and postpartum, but optimal dosing has been unclear. The Highlow trial evaluated dosing in 1110 pregnant individuals with a prior VTE receiving LMW heparin for VTE prophylaxis from the first trimester to six weeks postpartum [30]. Compared with weight-adjusted intermediate dosing, those assigned to daily fixed low-dose (60 mg) LMW heparin had a slightly higher rate of VTE (1 percent in both groups antepartum, 2 versus 1 percent postpartum); the difference did not reach statistical significance. Bleeding risk was 4 percent in each group. While we continue to perform an individualized risk assessment for each patient, this trial provides reassurance for the efficacy of fixed low-dose LMH heparin, especially antenatally. (See "Use of anticoagulants during pregnancy and postpartum", section on 'LMW heparin'.)

Low molecular weight heparin dose adjustment in trauma patients (October 2022)

Low molecular weight heparin (LMWH) is administered to adult trauma patients to reduce the risk of venous thromboembolism (VTE), but questions remain about dosing and monitoring. In a meta-analysis of observational studies including heterogeneous multisystem trauma patients, those who attained prophylactic anti-Xa levels had a lower rate of VTE than those who did not [31]. However, dose adjustment to achieve prophylactic anti-Xa levels paradoxically did not reduce VTE compared with standard fixed enoxaparin dosing. While there is likely a role for LMWH dose adjustment based on anti-Xa levels in trauma patients, the optimal protocol and trauma population that would benefit have not been determined. (See "Venous thromboembolism risk and prevention in the severely injured trauma patient", section on 'Monitoring and dose adjustment'.)

Aspirin versus enoxaparin to prevent venous thromboembolism after hip or knee arthroplasty (September 2022)

The role of aspirin as a sole agent for venous thromboembolism (VTE) prophylaxis in adult patients undergoing total hip or knee arthroplasty (THA, TKA) is debated. In a recent, randomized crossover trial of over 9700 patients following THA or TKA that compared aspirin (100 mg orally per day) to enoxaparin (40 mg subcutaneously per day), symptomatic distal deep vein thrombosis was more common in patients receiving aspirin (2.4 versus 1.2 percent) [32]. There was no difference in the rates of major bleeding (< 0.5 percent) and death. Study limitations include the trial being stopped early for harm and lack of blinding of hospitals to treatment allocation. Nevertheless, these findings indicate that aspirin alone is inferior to enoxaparin and supports our practice of not using aspirin as the sole agent for VTE prophylaxis in patients following THA or TKA. (See "Prevention of venous thromboembolism in adults undergoing hip fracture repair or hip or knee replacement", section on 'Aspirin'.)


Position statement on obstructive sleep apnea in the transportation industry (October 2022)

The American Academy of Sleep Medicine (AASM) has published a position statement on recognizing and treating obstructive sleep apnea (OSA) in commercial drivers and other individuals in safety-sensitive transportation occupations [33,34]. The documents outline roles for key stakeholders, including legislators, employers, law enforcement, payers, health care professionals, and vehicle operators. The AASM recommends that commercial drivers be referred to a sleep medicine specialist for clinical sleep evaluation and diagnostic testing in the presence of a body mass index (BMI) ≥40 kg/m2, fatigue or sleepiness while on duty, involvement in a sleepiness-related crash or accident, or a BMI ≥33 kg/m2 plus either type 2 diabetes or hypertension requiring two or more medications. (See "Drowsy driving: Risks, evaluation, and management", section on 'Special considerations in commercial drivers'.)

Positive airway pressure therapy for obstructive sleep apnea in patients with COPD (August 2022)

Up to one-third of patients with chronic obstructive pulmonary disease (COPD) have coexisting obstructive sleep apnea (OSA); similar to the general population, positive airway pressure (PAP) is the mainstay of therapy, but outcomes in this population have not been assessed in large studies. In a health insurance claims database study of 6810 patients with COPD and OSA who were prescribed PAP, adherence was assessed with PAP user data, and propensity score matching was used to control for confounding [35]. During two years of PAP therapy, compared with the year before therapy, PAP-adherent patients showed greater reductions in emergency department visits, inpatient hospitalizations, and severe acute exacerbations compared with nonadherent patients. While randomized trials in patients with COPD are needed, these results support the ability of PAP to improve patient-important outcomes. (See "Sleep-related breathing disorders in COPD", section on 'Initiating positive airway pressure'.)

Network meta-analysis of insomnia medications in adults (July 2022)

A large number of medications spanning multiple classes are available for treatment of insomnia, but few long-term or comparative trials have been performed. This was illustrated by a network meta-analysis, which identified 154 placebo-controlled randomized trials of 30 different medications for insomnia in nearly 45,000 participants, of which only five trials were longer than four weeks, and nearly all comparisons relied on indirect evidence and a small subset of the total number of trials [36]. While the study concluded that eszopiclone, a benzodiazepine receptor agonist (BZRA), and lemborexant, a dual orexin receptor antagonist (DORA), appeared to be the most favorable medications for overall efficacy and tolerability, confidence was limited by known adverse effects of BZRAs and inconclusive long-term safety data for DORAs. In addition, patients with insomnia seen in clinical practice represent a broader population than those enrolled in clinical trials, and treatment decisions must weigh individual risks and benefits of medications along with all other available therapies. (See "Pharmacotherapy for insomnia in adults", section on 'Our approach'.)


Vaccination status and prevalence of "long COVID" symptoms (July 2022)

In a new prospective observational cohort study of 2560 patients with mild COVID-19, COVID-19 vaccination was associated with a decreased prevalence of postacute sequelae of SARS-CoV-2 infection (PASC) in a dose-dependent fashion (three doses 16 percent, two doses 17.4 percent, and one dose 30 percent) compared with unvaccinated individuals (42.8 percent) [37]. This finding appeared to be independent from the COVID-19 variant. This study provides additional evidence that COVID-19 vaccination, in addition to reducing the risk of COVID-19 infection, may also decrease PASC in vaccinated patients with mild infection. (See "COVID-19: Evaluation and management of adults with persistent symptoms following acute illness ("Long COVID")", section on 'Prevention of post-COVID conditions'.)

Risk of long COVID in Delta versus Omicron variants (June 2022)

Persistent symptoms following acute COVID-19 infection (eg, long COVID) are common. Recent evidence suggests that the prevalence of persistent symptoms may vary depending on the COVID-19 variant. In an observational study including over 97,000 vaccinated individuals in the United Kingdom, subsequent infection with the Omicron variant was associated with a lower risk of developing persistent symptoms compared with Delta (4.5 versus 10.8 percent) [38]. Findings were consistent regardless of the interval between vaccination and infection. However, methodologic issues (eg, self-reporting through an electronic "app" and shorter duration of follow-up for Omicron versus Delta patients) limit the interpretation of these findings, and further research is needed. (See "COVID-19: Evaluation and management of adults with persistent symptoms following acute illness ("Long COVID")", section on 'Persistent symptoms'.)

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