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.

NEUROLOGY (May 2024)

Reversal strategy for intracerebral hemorrhage associated with direct factor Xa inhibitors

●For direct factor Xa inhibitor-associated intracerebral hemorrhage, we suggest either andexanet alfa or 4-factor prothrombin complex concentrate (PCC) based on the severity of hemorrhage, local protocols, and availability (Grade 2C). Andexanet may restore hemostasis more effectively than PCC but is associated with higher thrombotic risk.

The optimal reversal strategy for direct factor Xa inhibitors (apixaban, edoxaban, rivaroxaban) in acute intracerebral hemorrhage (ICH) is uncertain. In the ANNEXA-I trial, which randomly assigned 530 patients with factor Xa inhibitor-associated ICH to andexanet alfa or standard care (typically including a prothrombin complex concentrate [PCC]), patients assigned to andexanet had higher rates of hemostasis than those assigned to standard therapy (67 versus 53 percent) [1]. However, thrombotic events, including ischemic stroke and myocardial infarction, were more common with andexanet (10.3 versus 5.6 percent). Mortality and functional outcomes at 30 days were similar. Based on these results, we individualize selection of andexanet alfa or PCC for direct factor Xa inhibitor reversal in acute ICH and other life-threatening bleeding; previously, we favored andexanet in most cases. Andexanet may restore hemostasis more effectively than PCC but is associated with higher thrombotic risk. (See "Reversal of anticoagulation in intracranial hemorrhage", section on 'Reversal agent options'.)

PULMONARY AND CRITICAL CARE MEDICINE (May 2024)

Revised diagnostic criteria for allergic bronchopulmonary aspergillosis

●There is no individual test to establish the diagnosis of allergic bronchopulmonary aspergillosis, and the diagnosis is usually confirmed by a combination of clinical, radiographic, and immunologic findings. We favor using the 2024 revised diagnostic criteria proposed by the International Society for Human and Animal Mycology (ISHAM) that simplify prior diagnostic schema.

Allergic bronchopulmonary aspergillosis (ABPA), a complex hypersensitivity reaction to airway colonization with Aspergillus fumigatus, can be hard to distinguish from difficult-to-treat asthma or cystic fibrosis. The International Society for Human and Animal Mycology (ISHAM) working group for ABPA recently published revised diagnostic criteria (table 1) that make some key changes to improve the sensitivity and specificity of the diagnosis [2]:

•Total serum immunoglobulin (Ig) E levels of ≥500 international units/mL are sufficient for the diagnosis, rather than the previously higher threshold of 1000 international units/mL.

•Elevated Aspergillus IgG levels by enzyme immunoassay or lateral flow assay are more sensitive for detecting sensitivity to Aspergillus antigens and should be used preferentially over Aspergillus serum precipitins.

We agree with the revised ISHAM diagnostic approach. (See "Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis", section on 'Diagnostic criteria'.)

PRIMARY CARE (ADULT) (March 2024)

Tirzepatide for weight loss in adults

●For individuals who are overweight or obese in whom pharmacologic therapy is indicated, we suggest subcutaneous tirzepatide or semaglutide rather than other agents (Grade 2C). The selection between tirzepatide and semaglutide depends on patient preferences and comorbidities.

The US Food and Drug Administration recently approved subcutaneous tirzepatide, a dual glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, for chronic weight management [3]. Two randomized trials in adults with obesity demonstrated mean losses of 15 to 21 percent body weight with the highest dose of tirzepatide (15 mg weekly) [4,5]. In the larger of the two trials, over 80 percent of participants in all tirzepatide treatment groups (5 to 15 mg weekly) lost ≥5 percent of body weight, compared with 35 percent of those assigned to placebo [4]. Dose-related gastrointestinal side effects (nausea, diarrhea, constipation) were common but generally mild. Although direct comparisons are limited, the magnitude of weight loss with tirzepatide appears greater than that with other agents; thus, we consider tirzepatide a preferred medication for chronic weight management. (See "Obesity in adults: Drug therapy", section on 'Efficacy for weight loss'.)

PULMONARY AND CRITICAL CARE MEDICINE (December 2023)

Thyroid hormone administration in deceased organ donors

●For hemodynamically unstable, brain-dead organ donors, we suggest against the use of thyroid hormone (Grade 2C). Thyroid hormone supplementation has little to no effect on organ procurement or graft outcomes, but it increases the rates of hypertension and tachycardia in deceased donors.

Thyroid hormone administration has been a longstanding component of some organ procurement protocols due to concern that acute hypothyroidism might contribute to hemodynamic instability and left ventricular dysfunction, reducing heart and other organ procurement; however, evidence for the practice has been inconsistent. In a recent trial of 838 hemodynamically unstable, brain-dead donors assigned to receive a levothyroxine infusion or saline placebo, there was little to no difference in number of hearts transplanted or 30-day cardiac graft survival [6]. Recovery of other organs was similarly unaffected. More cases of severe hypertension or tachycardia occurred in the levothyroxine group than in the saline group. Based on these data, we suggest avoiding thyroid hormone administration in deceased organ donors. (See "Management of the deceased organ donor", section on 'Thyroid hormone'.)

OBSTETRICS, GYNECOLOGY AND WOMEN'S HEALTH (October 2023)

Valacyclovir for prevention of congenital cytomegalovirus infection

●For pregnant patients with periconception or first-trimester primary cytomegalovirus infection, we suggest high-dose oral valacyclovir rather than no therapy (Grade 2C).

Emerging evidence suggests that maternal administration of valacyclovir for primary cytomegalovirus (CMV) infection substantially reduces the risk of congenital CMV infection, especially if begun prior to 14 weeks of gestation and within 8 weeks of the maternal infection. In a 2023 individual patient data meta-analysis (one randomized trial, two observational studies), maternal valacyclovir administration upon diagnosis of periconception or first-trimester primary CMV infection was associated with a 66 percent reduction in congenital CMV (11 versus 25 percent) [7]. We suggest high-dose oral valacyclovir (8g per day) for patients with a primary CMV infection in early pregnancy after a comprehensive discussion of the potential benefits and risks (eg, 2 percent risk of reversible maternal kidney failure). (See "Cytomegalovirus infection in pregnancy", section on 'Antiviral medication'.)

OBSTETRICS, GYNECOLOGY AND WOMEN'S HEALTH (April 2023, Modified October 2023)

Respiratory syncytial virus vaccination in pregnancy

●In settings where nirsevimab is not available, for pregnant individuals between 32 0/6 and 36 6/7 weeks of gestation in September through January (in the northern hemisphere), we suggest vaccination with a single intramuscular injection of the inactivated nonadjuvanted recombinant respiratory syncytial virus (RSV) vaccine (RSVPreF; Abrysvo) (Grade 2B). In settings where both are available, the optimal preventive strategy remains uncertain. For such patients, both options should be discussed and shared decision-making undertaken.

Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality in infants. In October 2023, the United States Centers for Disease Control and Prevention, along with guidelines from other expert groups, endorsed RSV vaccination of pregnant individuals to reduce severe RSV infections in their infants [8-11]. Nirsevimab, a monoclonal antibody that can be given to infants postnatally to reduce the risk of severe RSV, has also been recently approved and endorsed by expert guidance panels. In settings where nirsevimab is not available, we suggest vaccination of pregnant individuals between 32 0/6 and 36 6/7 weeks of gestation in September through January (in the northern hemisphere) with inactivated nonadjuvanted recombinant RSV vaccine (RSVPreF; Abrysvo). In settings where both maternal vaccination and nirsevimab are available, the optimal preventive strategy remains uncertain, and, in most cases, it will not be possible to use both. For such patients, both options should be discussed and shared decision-making undertaken. (See "Immunizations during pregnancy", section on 'Choosing the optimal strategy'.)

PEDIATRICS (October 2023)

Immunoprophylaxis for severe respiratory syncytial virus in infants

●In all infants younger than eight months who are born during the respiratory syncytial virus (RSV) season or are entering their first RSV season, we recommend one dose of nirsevimab prophylaxis rather than no prophylaxis (Grade 1B), unless the birthing parent received RSV vaccination at least 14 days prior to birth.

Nirsevimab is a new monoclonal antibody that targets the prefusion conformation of the respiratory syncytial virus (RSV) F glycoprotein [12]. It has a longer half-life than palivizumab, an existing antibody that requires five monthly injections to provide immunoprophylaxis against severe RSV infection. The efficacy and safety of nirsevimab were demonstrated in two randomized placebo-controlled trials, one involving 1490 infants ≥35 weeks' gestation and the other involving >1400 preterm infants (29 to <35 weeks' gestation) [13,14]. In both trials, a single intramuscular dose of nirsevimab lowered rates of RSV-related medical evaluation and hospital admissions for RSV. In line with American Academy of Pediatrics and United States Centers for Disease Control and Prevention guidance, we now recommend that infants <8 months old receive one dose of nirsevimab during their first RSV season if the birthing parent did not receive RSV vaccination between 32 and 36 weeks of gestation and at least 14 days prior to delivery. Palivizumab may be used in high-risk infants if nirsevimab is not available. (See "Respiratory syncytial virus infection: Prevention in infants and children", section on 'Immunoprophylaxis'.)

INFECTIOUS DISEASES (September 2023)

Statins for primary prevention of cardiovascular disease in persons with HIV

●For persons ≥40 years of age with HIV and a low-density lipoprotein cholesterol ≥190 and/or a 10-year ASCVD score ≥5 percent, we recommend a statin (Grade 1B). For those with lower risk, we also discuss statin use, but the absolute benefit is smaller.

HIV infection is associated with an excess risk of cardiovascular disease. A randomized trial evaluated the efficacy of lipid-lowering therapy with pitavastatin for primary prevention in over 7700 persons with HIV ≥40 years of age receiving antiretroviral therapy who had a 10-year atherosclerotic cardiovascular disease (ASCVD) risk score <15 percent [15]. Pitavastatin reduced the relative risk of major cardiovascular events (eg, myocardial infarction, stroke) by 35 percent compared with placebo; the trial was stopped early for this apparent benefit. Based on these data, we now advise statins in all persons ≥40 years of age with an ASCVD score ≥5 percent; for those with lower baseline risk, we also discuss statin use, although the absolute benefit is smaller. For persons younger than 40 and older than 75 years of age, our approach is the same as in persons without HIV. (See "Management of cardiovascular risk (including dyslipidemia) in patients with HIV", section on 'Indications for statins'.)