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 (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 [1]. 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) [2]. 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 [3-6]. 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 [7]. 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) [8,9]. 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)

Updated COVID-19 mRNA vaccine recommendations

●For all individuals aged six months and older, we suggest a 2023-2024 formula COVID-19 vaccine (Grade 2C). Individuals who are at highest risk of severe outcomes with COVID-19, specifically individuals 65 years or older, immunocompromised individuals, and individuals with multiple medical comorbidities (table 1), are most likely to benefit from vaccination.

The US Food and Drug Administration and Centers for Disease Control and Prevention have updated COVID-19 vaccine authorizations and recommendations [10,11]. Available COVID-19 vaccines have been updated to target Omicron variant XBB.1.5 (Moderna COVID-19 vaccine 2023-2024 formula, Pfizer COVID-19 vaccine 2023-2024 formula, and Novavax 2023-2024 formula); bivalent vaccines are no longer available. An updated 2023-2024 formula vaccine is recommended for all individuals aged six months and older. Immunocompetent individuals five years and older should receive one updated vaccine, regardless of prior vaccination history. For individuals who are four years or younger or have an immunocompromising condition (table 1), the number of recommended updated vaccines depends on their vaccination history. Our approach to COVID-19 vaccination is consistent with these recommendations. (See "COVID-19: Vaccines", section on 'Indications and vaccine selection' and "COVID-19: Vaccines", section on 'Benefits of vaccination'.)

INFECTIOUS DISEASES (September 2023)

Statins for primary prevention of cardiovascular disease in persons with HIV

●For persons ≥40 years of age with HIV and an low-density lipoprotein cholesterol ≥190 and/or a 10-year ASCVD score ≥7.5 percent, we recommend a statin (Grade 1B). We also suggest a statin for such patients with a 10-year ASCVD score of 5 to 7.4 percent (Grade 2B). 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 [12]. 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, particularly if the score is ≥7.5 percent; for those with lower baseline risk, we also discuss statin use, although the absolute benefit is smaller. For persons younger than 40 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'.)

INFECTIOUS DISEASES; PRIMARY CARE (ADULT); FAMILY MEDICINE AND GENERAL PRACTICE (April 2023)

Expanded recommendations for hepatitis B virus screening in adults

●For most individuals without risk factors for hepatitis B virus (HBV), we suggest one-time HBV screening for those ≥18 years of age (Grade 2C). For adults at increased risk for acquiring HBV (table 1), we recommend HBV screening (Grade 1B).

Screening for hepatitis B virus (HBV) in adults has traditionally been recommended for those with risk factors (table 2). In March 2023, the United States Centers for Disease Control and Prevention expanded their recommendations to include universal screening for persons ≥18 years of age at least once during their lifetime, regardless of risk [13]. The rationale is the prevalence of chronic HBV infection in the general population (0.4 percent), the low vaccination rates in adults, and the harms of missed infection such as fulminant hepatitis and liver cancer. Testing should include hepatitis B surface antigen, hepatitis B surface antibody (anti-HB), and total hepatitis B core antibody. We support universal screening; however, screening is generally not needed if an HBV vaccine series has been completed and there is serologic evidence of immunity (anti-HBs ≥10 milli-international units/mL). (See "Hepatitis B virus: Screening and diagnosis in adults", section on 'Individuals without known risk for HBV infection'.)

ALLERGY AND IMMUNOLOGY (March 2023, Modified April 2023)

Cow's milk elimination alone for eosinophilic esophagitis

●In patients with eosinophilic esophagitis who opt for a dietary approach to treatment, we suggest elimination of cow's milk (in all its forms) and cross-reacting mammalian milk rather than simultaneous removal of multiple foods (Grade 2C).

Dietary treatment of eosinophilic esophagitis (EoE) traditionally has involved removal of multiple foods/food groups simultaneously. However, this approach is associated with poor adherence and can cause nutritional deficiencies. In a multicenter randomized trial of 129 adults with EoE that compared elimination of mammalian milk (1 food elimination diet [FED]) with removal of six foods/food groups (6FED), rates of histologic remission were similar between the two groups at six weeks (34 versus 40 percent, respectively) [14]. Improvements in disease-relatedquality-of-life scores and peak eosinophil counts were also similar. These results confirm earlier findings in a pediatric trial. For most patients with EoE who opt for a dietary approach to treatment, we suggest an initial empiric elimination diet of cow's milk (all forms of dairy/milk) plus cross-reacting mammalian milk (eg, goat's milk). (See "Dietary management of eosinophilic esophagitis", section on 'Efficacy of different dietary approaches'.)

NEUROLOGY (February 2023)

Mechanical thrombectomy for large ischemic core infarcts

●For patients with acute ischemic stroke, we recommend treatment with intra-arterial mechanical thrombectomy (MT), whether or not the patient received treatment with intravenous thrombolytic therapy, if the following conditions are met (Grade 1B): Brain imaging using CT without contrast or diffusion-weighted MRI (DWI) excludes hemorrhage and is consistent with an Alberta Stroke Program Early CT Score (ASPECTS) ≥3; CT angiography (CTA) or MR angiography (MRA) demonstrates a proximal large artery occlusion in the anterior circulation as the cause of the ischemic stroke; the patient has a persistent, potentially disabling neurologic deficit (eg, a National Institutes of Health Stroke Scale [NIHSS] score ≥6); the patient can start treatment (femoral puncture) within 24 hours of the time last known to be well. This recommendation applies when thrombectomy is performed at a stroke center with appropriate expertise in the use of endovascular therapy. Benefit may be most likely when imaging confirms the presence of salvageable brain tissue (eg, a mismatch by DAWN or DEFUSE 3 criteria).

Mechanical thrombectomy (MT) for acute ischemic stroke due to a large artery occlusion in the anterior circulation has been limited to patients with a small- to moderate-sized core infarct at baseline. The exclusion of patients with large core infarcts was first challenged in 2022 by results from the RESCUE-Japan LIMIT trial. The recent SELECT2 and ANGEL-ASPECT trials now confirm that MT compared with medical treatment alone improves outcomes for patients with a large ischemic core infarct (defined by an Alberta Stroke Program Early CT Score [ASPECTS] of 3 to 5 or a core volume ≥50 ml) [15,16]. As an example, the SELECT2 trial showed that functional independence for patients with large infarcts was more likely with MT than with medical care alone (20 versus 7 percent) [15]. Based on these results, in addition to previously defined eligible groups, we also recommend MT for patients who have a large ischemic core infarct as defined in these trials and can start treatment within 24 hours of the time last known to be well. (See "Mechanical thrombectomy for acute ischemic stroke", section on 'Benefit for large core infarcts'.)