Practice Changing UpDates

INTRODUCTION — This section highlights selected specific new recommendations and/or updates that we anticipate may change usual clinical practice. Practice Changing UpDates focus on changes that may have significant and broad impact on practice, and therefore do not represent all updates that affect practice. These Practice Changing UpDates, reflecting important changes to UpToDate over the past year, are presented chronologically, and are discussed in greater detail in the identified topic reviews.

PULMONARY AND CRITICAL CARE MEDICINE (January 2023)

New GOLD strategy for initial COPD pharmacologic management

●For patients with COPD who are less symptomatic and at low risk of exacerbation (group A), we suggest a long-acting bronchodilator rather than short-acting bronchodilators alone (Grade 2B). For patients with COPD who are more symptomatic or have a high risk of exacerbation (Groups B and E), we suggest initial treatment with dual long-acting bronchodilator therapy rather than a single long-acting bronchodilator alone (Grade 2C).

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 report identifies key changes for patients with COPD [1], specifically more aggressive initial bronchodilator therapy:

•Single-agent long-acting bronchodilator therapy for less severe symptoms and low exacerbation risk (Group A).

•Dual long-acting bronchodilator therapy for more severe symptoms and low exacerbation risk (Group B).

•Dual long-acting bronchodilator therapy for high exacerbation risk, regardless of symptoms (Group E, replacing previous Groups C and D categories).

It also redefines a COPD exacerbation as an event characterized by dyspnea and/or cough and sputum that worsens over ≤14 days with possible tachypnea and/or tachycardia caused by airway infection, pollution, or other insult to the airways. This new definition decouples exacerbations from their treatment, which had confounded earlier approaches. A new classification for severity of exacerbations was also outlined. (See "COPD exacerbations: Clinical manifestations and evaluation" and "Stable COPD: Initial pharmacologic management", section on 'Assessing disease pattern and severity'.)

PEDIATRICS (November 2022, Modified January 2023)

Semaglutide for obesity in adolescents

●For adolescents with refractory obesity who opt for pharmacologic therapy, we suggest subcutaneous semaglutide rather than other agents (Grade 2C).

Glucagon-like peptide (GLP-1) analogs are important options for treatment of type 2 diabetes and/or obesity in adults. In a 68-week randomized trial in 201 adolescents with obesity, patients assigned to weekly subcutaneous semaglutide, a GLP-1 analog, had substantial weight loss compared with lifestyle intervention alone (17.7 kg greater weight loss compared with placebo; 6 kg/m² greater decrease in body mass index [BMI]) [2]. Gastrointestinal adverse events were common in both groups but were generally mild and rarely led to treatment discontinuation. While head-to-head trials have not been performed in adolescents, indirect evidence suggests greater weight loss with semaglutide than the alternatives, including liraglutide and metformin. Based on these findings, we now suggest semaglutide over other agents for pharmacotherapy of obesity in selected adolescents. (See "Prevention and management of childhood obesity in the primary care setting", section on 'Pharmacotherapy'.)

INFECTIOUS DISEASES (September 2022, Modified December 2022)

Booster doses with the bivalent COVID-19 mRNA vaccines

●For individuals who have received a primary COVID-19 vaccine series, we recommend a booster dose with a bivalent mRNA vaccine when eligible (Grade 1B). For individuals ≥5 years old who have received a primary COVID-19 vaccine series as well as booster doses with a monovalent vaccine, we suggest a booster dose with a bivalent mRNA vaccine (Grade 2C).

Booster doses of COVID-19 vaccines are a strategy to improve effectiveness in the setting of waning immunity and immune evasion from circulating SARS-CoV-2 variants. The US Food and Drug Administration authorized two bivalent mRNA booster vaccines that target the spike proteins of both the original SARS-CoV-2 strain and the Omicron B.4/B.5 variants (figure 1 and figure 2) [3,4]. The Centers for Disease Control and Prevention (CDC) now recommends that all individuals ≥5 years old who have completed a primary COVID-19 vaccine series (including those who already received booster doses with monovalent vaccines) receive a single booster dose with one of the bivalent vaccines at least two months after the last vaccine dose; bivalent booster recommendations for children younger than five years old depend on the primary series vaccine received (table 1) [5]. Our approach is consistent with CDC recommendations. Although clinical data evaluating bivalent vaccines are limited, their use is supported by indirect evidence from trials and observational studies in which monovalent booster doses improved vaccine efficacy against infection and severe disease and by studies that indicate at least comparable immunogenicity with bivalent versus monovalent formulations. (See "COVID-19: Vaccines", section on 'Role of booster vaccinations'.)

PSYCHIATRY (December 2022)

Screening for anxiety in children and adolescents

●We suggest screening for anxiety disorders in individuals between age 8 and 18 years (Grade 2C).

Anxiety in children and adolescents interferes with social, emotional, and academic development. The United States Preventive Services Task Force (USPSTF) now recommends screening for anxiety in all individuals aged 8 to 18 years old [6]. This updated recommendation is supported by a meta-analysis that included 39 studies with 6065 subjects in that age range and showed moderate accuracy of screening tools and moderate benefit of treatment on symptom response and disease remission [7]. The harms associated with screening and subsequent treatment were minimal. Our approach is consistent with these recommendations. We use the Screen for Child Anxiety-Related Emotional Disorders (SCARED) tool, which is available in the public domain. (See "Anxiety disorders in children and adolescents: Assessment and diagnosis", section on 'Screening'.)

INFECTIOUS DISEASES (December 2022)

First trimester treatment of malaria with artemisinin derivatives

●For treatment of uncomplicated chloroquine-resistant Plasmodium falciparum malaria during the first trimester, we suggest treatment with artemether-lumefantrine, rather than a quinine-based regimen (Grade 2B). We also suggest artemether-lumefantrine for chloroquine-resistant non-falciparum malaria during the first trimester (Grade 2C).

Artemisinin combination therapy (ACT) has become the preferred treatment for uncomplicated malaria in most patients, but use for treatment of chloroquine-resistant malaria in the first trimester has been avoided because of limited safety data. However, in a 2022 meta-analysis of prospective data from >700 pregnancies with confirmed first trimester exposure to ACT and >1000 pregnancies with confirmed first trimester exposure to non-ACTs, adverse pregnancy outcomes occurred less often among those who received ACT, although the result was not statistically significant (5.7 versus 8.9 percent; adjusted hazard ratio [aHR] 0.71, 95% CI 0.49-1.03) [8]. Artemether-lumefantrine accounted for 70 percent of the ACT exposures and was associated with a lower risk of adverse pregnancy outcome compared with oral quinine (4.8 versus 9.2 percent; aHR 0.58, 95% CI 0.36-0.92). Based on these data, we now suggest artemether-lumefantrine for treatment of chloroquine-resistant malaria during the first trimester. (See "Malaria in pregnancy: Prevention and treatment", section on 'Drug safety'.)

NEPHROLOGY AND HYPERTENSION (November 2022)

Finerenone in patients with diabetic kidney disease

●Among patients with type 2 diabetes who have measured or estimated albuminuria ≥30 mg/day despite an angiotensin inhibitor and a sodium-glucose co-transporter 2 (SGLT2) inhibitor, we suggest treatment with a nonsteroidal selective mineralocorticoid receptor antagonist (MRA, specifically finerenone) (Grade 2B), where available.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors and finerenone (a nonsteroidal mineralocorticoid receptor antagonist) prevent important adverse kidney and cardiovascular outcomes in patients with diabetic kidney disease (DKD). The 2022 guidelines from the American Diabetes Association (ADA) and the Kidney Disease: Improving Global Outcomes (KDIGO) on the treatment of patients with DKD advise the use of SGLT2 inhibitors in all patients with DKD; they also advise the use of finerenone in patients who have increased albuminuria despite treatment with an angiotensin inhibitor and an SGLT2 inhibitor [9,10]. We agree with these guidelines and now suggest use of finerenone in patients with albuminuria despite other recommended therapies, except when serum potassium is elevated (serum potassium >4.8 mEq/L or estimated glomerular filtration rate <25 mL/min/1.73 m²). (See "Treatment of diabetic kidney disease", section on 'Type 2 diabetes: Treat with additional kidney-protective therapy'.)

NEPHROLOGY AND HYPERTENSION (November 2022)

SGLT2 inhibitors in patients with nondiabetic proteinuric chronic kidney disease

●In patients with chronic nondiabetic kidney disease with proteinuria (albuminuria ≥300 mg/day or proteinuria ≥500 mg/day), we recommend treatment with a sodium-glucose co-transporter 2 (SGLT2) inhibitor (Grade 1B).

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are recommended in patients with diabetic kidney disease; previously, only one large trial examined their effects in nondiabetic chronic kidney disease. In the EMPA-KIDNEY trial, 6609 patients with estimated glomerular filtration rate (eGFR) 20 to 44 mL/min/1.73 m² (regardless of albuminuria) or 45 to 89 mL/min/1.73 m² (if albumin-to-creatinine ratio was at least 200 mg/g) were randomly assigned to empagliflozin 10 mg daily or placebo [11]. At two years, empagliflozin reduced the incidence of end-stage kidney disease, the incidence of a sustained decline in eGFR to <10 mL/min/1.73 m², and the incidence of a sustained decrease in eGFR of 40 percent or more; the risks of all-cause mortality and nonfatal cardiovascular events were similar between groups. The benefit from empagliflozin was larger in patients with albumin-to-creatinine ratio ≥300 mg/g and substantially less in patients with lower albumin excretion. We now recommend SGLT2 inhibitor therapy in patients with nondiabetic chronic kidney disease and albuminuria. (See "Overview of the management of chronic kidney disease in adults", section on 'Patients with proteinuria'.)

NEUROLOGY (October 2022)

Sodium phenylbutyrate-taurursodiol for amyotrophic lateral sclerosis

●For all patients with amyotrophic lateral sclerosis, we suggest treatment with sodium phenylbutyrate-taurursodiol (Grade 2B), in addition to riluzole and edaravone.

Sodium phenylbutyrate-taurursodiol (PB-TURSO) is a combination of two orally available drugs that each reduce neuronal cell death in preclinical models of amyotrophic lateral sclerosis (ALS). In a randomized trial of 137 patients with ALS (75 percent also taking riluzole and/or edaravone) who were within 18 months of symptom onset, patients assigned to PB-TURSO showed a slower median rate of monthly functional decline than those assigned to placebo by 24-week follow-up [12]. There were nonsignificant trends toward slower decline in both vital capacity and muscle strength with treatment. In a subsequent analysis of patients who continued open-label treatment (up to 35 months), those originally randomized to PB-TURSO had a longer median time to tracheostomy (26 versus 19 months) and a longer median time to first hospitalization [13]. Based on these results, the combination product received regulatory approval in the United States and Canada [14,15]. We now suggest use of PB-TURSO for all patients with ALS, along with riluzole (prioritized as initial therapy) and edaravone. (See "Disease-modifying treatment of amyotrophic lateral sclerosis", section on 'Efficacy'.)

GENERAL SURGERY (September 2022)

Role of wound packing after drainage of perianal and perirectal abscess

●For most patients with a perianal or perirectal abscess, we suggest not packing the wound after drainage (Grade 2C).

After incision and drainage of a perianal or perirectal abscess, it is common practice to pack the wound, under the assumption that this will facilitate further drainage by wicking and prevent premature skin closure. In the PPAC2 trial of 443 patients with a primary perianal abscess, nonpacking, compared with packing, resulted in similar rates of fistula formation (11 versus 15 percent) and abscess recurrence (6 versus 3 percent), differences that were not statistically significant [16]. However, the nonpacking group had lower average pain scores (28 versus 38 on a 100-point visual analog scale). Given these and similar findings from two earlier small trials, we now suggest not packing the wound after drainage of perianal or perirectal abscess. (See "Perianal and perirectal abscess", section on 'Role of wound packing'.)

CARDIOVASCULAR MEDICINE (September 2022)

Anticoagulation for rheumatic mitral stenosis with atrial fibrillation

●For patients with rheumatic mitral stenosis requiring anticoagulation (for atrial fibrillation, left atrial thrombus, or a prior embolic event), we recommend chronic anticoagulation with a vitamin K antagonist (eg, warfarin) rather than with a direct oral anticoagulant (Grade 1B). The target international normalized ratio is 2.5 (range 2.0 to 3.0).

Limited data have been available to guide anticoagulant choice in patients with rheumatic mitral stenosis and atrial fibrillation. A randomized trial enrolling over 4500 adults with rheumatic heart disease and atrial fibrillation found that the mortality and stroke rates were higher with rivaroxaban than with a vitamin K antagonist (VKA), and major bleeding rates were similar [17]. Based on these findings, for patients with rheumatic mitral stenosis and atrial fibrillation, we now recommend a VKA rather than a direct oral anticoagulant such as rivaroxaban. (See "Rheumatic mitral stenosis: Overview of management", section on 'Choice of anticoagulant'.)

PULMONARY AND CRITICAL CARE MEDICINE (August 2022)

Intravenous magnesium in severe COPD exacerbation

●For patients having an acute COPD exacerbation who experience limited benefit from short-acting inhaled bronchodilators, we suggest intravenous magnesium (Grade 2C).

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 [18]. 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'.)

NEPHROLOGY AND HYPERTENSION (June 2022)

Oral glucocorticoids for immunoglobulin A (IgA) nephropathy

●For patients with IgA nephropathy who are considered to be at high risk of disease progression (ie, proteinuria ≥1 g/day despite at least three months of optimized supportive care), we suggest treatment with glucocorticoids plus supportive care rather than supportive care alone (Grade 2B).

In patients with immunoglobulin A (IgA) nephropathy who are at high risk for progressive disease, the effect of glucocorticoids on clinical outcomes has been uncertain. In a randomized trial of over 500 patients with IgA nephropathy, proteinuria ≥1 g/day, and an estimated glomerular filtration rate of 20 to 120 mL/min per 1.73 m² after at least three months of supportive therapy, the addition of oral glucocorticoids (full- or reduced-dose) to supportive therapy slowed the decline of kidney function and reduced the risk of end-stage kidney disease compared with supportive therapy alone (19 versus 27 percent) [19]. Serious adverse events were more frequent with glucocorticoids than with placebo but occurred primarily among those receiving full rather than reduced doses of glucocorticoids. Based on these results, we now suggest use of glucocorticoids in most high-risk patients with IgA nephropathy. (See "IgA nephropathy: Treatment and prognosis", section on 'Glucocorticoid therapy'.)

INFECTIOUS DISEASES (June 2022)

COVID-19 vaccination in children 6 months and older

●For children aged 6 months to 11 years old, we recommend COVID-19 vaccination (Grade 1B).

As of June 2022, the US Food and Drug Administration (FDA) has authorized BNT162b2 (Pfizer COVID-19 vaccine) and mRNA-1273 (Moderna COVID-19 vaccine) for use in children 6 months and older. Trials in children 6 months to 11 years have demonstrated that these vaccines, given at lower doses, elicit neutralizing immune responses comparable to those in adolescents and adults following standard doses [20-22]. Vaccination also reduces the risk of symptomatic COVID-19 in these populations, although the estimates of effect vary, in part because of different variants prevalent during the trials. There were no cases of vaccine-associated myocarditis in the trials; the precise risk is uncertain but is expected to be lower than that seen in older individuals. We agree with recommendations from the Centers for Disease Control and Prevention to give BNT162b2 or mRNA-1273 to children ages 6 months to 11 years. Clinicians should be aware that the dose and formulation used for children are different than those for adolescents and adults (table 1). (See "COVID-19: Vaccines", section on 'Summary and recommendations'.)

INFECTIOUS DISEASES (February 2022, Modified May 2022)

Updated recommendations for pneumococcal vaccination in adults

●For all adults with an indication for pneumococcal vaccination (table 1), we suggest PCV20 rather than other vaccines (Grade 2C). For patients with immunocompromising conditions or risk for meningitis, some UpToDate authors also favor administering PPSV23 ≥8 weeks following the PCV20 dose.

In early 2022, the Advisory Committee on Immunization Practices (ACIP) updated guidance on pneumococcal vaccination to recommend either [23]:

•20-valent pneumococcal conjugate vaccine (PCV20) alone (newly available), or

•The combination of 15-valent pneumococcal conjugate vaccine (PCV15; newly available) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) at least a year afterward, except in high-risk individuals (eg, immunocompromising conditions, cochlear implant, or cerebrospinal fluid leak), in whom a shorter interval of ≥8 weeks may be used to maximize protection more quickly

Based largely on convenience, we now suggest PCV20 for all adults with indications for pneumococcal vaccination (table 2). Although the ACIP does not require it, some UpToDate authors also favor giving PPSV23 ≥8 weeks after PSV20 for immunocompromised patients and those with increased risk for meningitis in order to provide protection against serotypes present in PPSV23 that are absent from PCV20. (See "Pneumococcal vaccination in adults".)

OBSTETRICS, GYNECOLOGY AND WOMEN'S HEALTH (April 2022)

Treatment of chronic hypertension in pregnancy

●For pregnant patients with nonsevere chronic hypertension (based on medical history or systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg or both on at least two occasions at least four hours apart before 20 weeks of gestation), we recommend antihypertensive treatment (Grade 1B).

Traditionally, only severe chronic hypertension (blood pressure [BP] ≥160/110 mmHg) has been treated in pregnancy because of fetal safety concerns and lack of evidence of maternal benefit. In the Chronic Hypertension and Pregnancy (CHAP) trial, over 2400 pregnant people with nonsevere chronic hypertension (≥140/90 mmHg) were randomly assigned to active treatment (initiating/continuing antihypertensive treatment to keep BP <140/90 mmHg) or usual care (antihypertensive treatment only for BP ≥160/105 mmHg) [24]. Active treatment resulted in an 18 percent relative reduction in a composite adverse pregnancy outcome, including preeclampsia with severe features (23.3 versus 29.1 percent) and medically indicated preterm birth <35 weeks (12.2 versus 16.7 percent), with no adverse fetal effects. Based on this trial, we now recommend antihypertensive treatment for pregnant patients with chronic hypertension to keep BP <140/90 mmHg. We prefer labetalol or extended-release nifedipine. (See "Treatment of hypertension in pregnant and postpartum patients", section on 'Background'.)

ONCOLOGY (April 2022)

First-line therapy for high-risk, high-volume metastatic hormone-sensitive prostate cancer

●For most patients with metastatic hormone-sensitive, high-risk, high-volume prostate cancer who are candidates for docetaxel, we recommend androgen deprivation therapy (ADT) plus docetaxel and darolutamide rather than ADT plus docetaxel alone (Grade 1B). Abiraterone is a reasonable alternative to darolutamide with promising but currently less robust data, particularly in those with metachronous metastatic disease.

Docetaxel plus androgen deprivation therapy (ADT) is a standard approach for initial treatment of patients with hormone-sensitive, high-risk, high-volume metastatic prostate cancer. Two trials now demonstrate an overall survival benefit from the addition of a second systemic agent to ADT plus docetaxel. In the ARASENS trial, the addition of darolutamide to ADT plus docetaxel improved overall survival and all secondary endpoints without worsening treatment-related toxicity in men with metastatic castration-sensitive prostate cancer (CSPC), and the benefits were similar in most subgroups [25]. In the PEACE-1 trial, the addition of abiraterone to ADT plus docetaxel also improved survival over ADT plus docetaxel alone in patients with de novo metastatic CSPC [26]. Largely based on results from the ARASENS trial, the combination of darolutamide plus docetaxel is now approved in the United States for treatment of metastatic CSPC [27]. (See "Initial systemic therapy for advanced, recurrent, and metastatic noncastrate (castration-sensitive) prostate cancer".)

INFECTIOUS DISEASES (February 2022)

Tenofovir alafenamide now a preferred NRTI agent for pregnant individuals with HIV

●For most treatment-naïve individuals with HIV who are initiating antiretroviral therapy during pregnancy, we suggest tenofovir alafenamide-emtricitabine plus dolutegravir rather than other preferred three-drug combination regimens (Grade 2C).

Recommended antiretroviral regimens for individuals with HIV initiating treatment during pregnancy include two nucleoside reverse transcriptase inhibitor (NRTI) agents in conjunction with either an integrase inhibitor or a booster protease inhibitor. Based on accumulating safety and efficacy data in this population, the United States Department of Health and Human Services has added tenofovir alafenamide (TAF) to the list of preferred NRTIs to use for pregnant individuals with HIV [28]. In a recent trial, regimens containing TAF versus tenofovir disoproxil fumarate (TDF) resulted in similar virologic suppression rates, but TAF was associated with fewer adverse pregnancy outcomes. We generally initiate the NRTI combination of TAF-emtricitabine in this patient population unless there is significant concern for excessive gestational weight gain, in which case a TAF-containing regimen can be used. (See "Antiretroviral selection and management in pregnant women with HIV in resource-rich settings", section on 'Selecting the NRTI backbone'.)

PEDIATRICS (February 2022)

Duration of anticoagulation for low-risk provoked venous thromboembolism in pediatric patients

●For pediatric patients with provoked venous thromboembolism who meet low-risk criteria, we suggest six weeks of anticoagulant therapy rather than observation or shorter or longer courses of treatment (Grade 2C).

The optimal duration of anticoagulant therapy for children with venous thromboembolism (VTE) is uncertain. Usual practice has been to treat for three months based largely upon evidence from adult studies. However, a recent clinical trial suggests that six weeks of therapy is sufficient for most pediatric patients with low-risk provoked VTE (ie, attributable to a transient risk factor) [29]. The trial enrolled 417 children with provoked VTE (catheter-associated in 50 percent; infection-related in 30 percent; surgery- or trauma-related in 20 percent) who were randomly assigned to six weeks or three months of anticoagulant therapy. At one year, rates of VTE recurrence were similarly low in both groups (1.1 and 1.6 percent, respectively). Based upon these findings, we now suggest a six-week course of treatment for pediatric patients with provoked VTE who met all of the following low-risk criteria:

•No prior history of VTE

•The VTE is not severe or life-threatening

•The provoking risk factor resolves within six weeks

•The thrombus resolves or is nonocclusive within six weeks

For patients with provoked VTE who do not meet these criteria, we continue to suggest three months of therapy. (See "Venous thrombosis and thromboembolism (VTE) in children: Treatment, prevention, and outcome", section on 'Provoked VTE'.)