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.
INFECTIOUS DISEASES; PRIMARY CARE (ADULT); FAMILY MEDICINE AND GENERAL PRACTICE; OBSTETRICS, GYNECOLOGY AND WOMEN'S HEALTH (January 2021)
Single-dose ceftriaxone for treatment of gonococcal infections
●For suspected or confirmed uncomplicated urogenital or anorectal gonococcal infection, we suggest ceftriaxone in a single 500 mg intramuscular dose rather than other regimens (Grade 2C). For individuals who weigh ≥150 kg, we give a 1 g dose.
In the United States, the Centers for Disease Control and Prevention updated its guidance on treatment of gonococcal infections to recommend ceftriaxone as the preferred regimen, given as a single intramuscular dose of 500 mg for individuals who weigh <150 kg or 1 g for individuals who weigh ≥150 kg . Previous recommendations were for combination therapy with a lower dose of ceftriaxone plus azithromycin. However, the previous preference for combination therapy was based on a theoretical benefit, which is now outweighed by decreasing susceptibility to azithromycin in Neisseria gonorrhoeae. A higher dose of ceftriaxone is recommended because of concern that lower doses are unlikely to be effective against isolates with higher minimum inhibitory concentrations to ceftriaxone, which have increased in prevalence. Presumptive treatment of chlamydia with doxycycline is warranted if chlamydia coinfection has not been ruled out. We agree with these updated guidelines. (See "Treatment of uncomplicated Neisseria gonorrhoeae infections", section on '"High" dose intramuscular ceftriaxone'.)
INFECTIOUS DISEASES (November 2020, Modified December 2020)
Vaccines to prevent symptomatic SARS-CoV-2 infection
●For individuals who are eligible for vaccination according to local allocation priorities, we recommend vaccination with one of the COVID-19 mRNA vaccines, BNT162b2 (Pfizer-BioNTech COVID-19 vaccine) or mRNA 1273 (Moderna COVID-19 vaccine) (Grade 1B).
Vaccines to prevent SARS-CoV-2 infection are considered the most promising approach for controlling the COVID-19 pandemic. Various vaccines are becoming available in different countries; the COVID-19 mRNA vaccines BNT162b2 (Pfizer-BioNTech COVID-19 vaccine) and mRNA 1273 (Moderna COVID-19 vaccine) received emergency use authorization in the United States in December 2020 [2,3]. Each is given as two intramuscular doses separated by a few weeks. In large placebo-controlled trials, these vaccine had 95 percent efficacy in preventing laboratory-confirmed symptomatic COVID-19 after the second dose . Local and systemic adverse effects (pain, fever, fatigue, headache) are common but usually nonsevere. Initial vaccine supplies are limited; in the United States, allocation priorities are determined at the state level. (See "Coronavirus disease 2019 (COVID-19): Vaccines to prevent SARS-CoV-2 infection".)
INFECTIOUS DISEASES (May 2020, Modified December 2020)
Dexamethasone and remdesivir for COVID-19
●For hospitalized patients with severe COVID-19 who are receiving supplemental oxygen (including those who are on high-flow oxygen and noninvasive ventilation), we suggest low-dose dexamethasone and, if available, remdesivir (Grade 2C).
For hospitalized patients with severe COVID-19 who require mechanical ventilation or ECMO, we recommend low-dose dexamethasone (Grade 1B). We suggest not routinely using remdesivir in this population (Grade 2C).
If dexamethasone is not available, other glucocorticoids at equivalent doses are reasonable alternatives.
Randomized trials suggest that glucocorticoids (in particular dexamethasone) have a mortality benefit in patients with COVID-19. Remdesivir, a novel antiviral may hasten time to recovery but has not clearly been demonstrated to reduce mortality:
•Meta-analyses suggest that glucocorticoids can reduce mortality in patients with severe COVID-19 [5,6]. Most of the data included in these analyses come from a randomized, open-label trial of >9000 patients hospitalized with COVID-19 in the United Kingdom, in which low-dose dexamethasone reduced 28-day mortality compared with usual care alone (21.6 versus 24.6 percent) . In subgroup analysis, the relative reduction in mortality appeared greater among patients on invasive mechanical ventilation than among those on noninvasive oxygen therapy. A mortality benefit was not seen among patients who did not require respiratory support.
•Data on remdesivir are mixed. In an interim report of the WHO-sponsored, multinational SOLIDARITY trial of >5000 hospitalized patients, open-label remdesivir did not reduce 28-day mortality . Another multinational trial of >1000 hospitalized patients also did not demonstrate an overall mortality benefit with remdesivir, although there was reduced mortality among patients who required supplemental oxygen but were not on high-flow oxygen or greater support . Remdesivir also resulted in faster time to recovery in that trial.
Uncertainties remain regarding optimal use of these agents. Nevertheless, for hospitalized patients with severe COVID-19 who require oxygen support, we use dexamethasone with or without remdesivir, depending on the level of support needed. (See "Coronavirus disease 2019 (COVID-19): Management in hospitalized adults", section on 'Severe (including critical) disease'.)
PRIMARY CARE (ADULT) (October 2020)
Colchicine in patients with stable coronary artery disease
Chronic inflammation is a risk factor for coronary artery disease events such as myocardial infarction, and colchicine has well documented anti-inflammatory effects. The LoDoCo2 trial randomly assigned over 5500 patients with chronic coronary disease to 0.5 mg of colchicine once daily or placebo . After a median follow-up of nearly two and half years, those assigned to colchicine had a lower risk of myocardial infarction (3.0 versus 4.2 percent) and ischemia-driven coronary artery revascularization (4.9 versus 6.4 percent) compared with the control group. Treatment was well tolerated aside from a small increase in myalgias. We suggest adding colchicine 0.5 mg (or 0.6 mg) once daily to other secondary preventive strategies in patients with stable coronary artery disease. (See "Overview of the prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk", section on 'Colchicine'.)
CARDIOVASCULAR MEDICINE (October 2020)
Antiplatelet therapy for transcatheter aortic valve implantation
●For patients undergoing transcatheter aortic valve implantation (TAVI) who lack a concurrent indication for dual antiplatelet therapy, we suggest treatment with a single antiplatelet agent (aspirin 75 to 100 mg daily or clopidogrel 75 mg daily) for life rather than dual antiplatelet therapy (Grade 2B).
The optimum antithrombotic regimen for patients undergoing transcatheter aortic valve implantation (TAVI) has been uncertain. A randomized controlled trial of over 660 patients undergoing TAVI found lower bleeding risk and similar stroke risk at one year with single antiplatelet therapy compared with dual antiplatelet therapy for the initial three months following the procedure . These findings are similar to those of a previous network meta-analysis, which included three smaller trials and observational studies totaling over 20,000 patients. Based on the accumulated data showing similar thrombotic outcomes and lower bleeding risk, we now suggest single agent rather than dual antiplatelet therapy for life in most patients undergoing TAVI who lack a concurrent indication for antithrombotic therapy. However, intermediate term dual antiplatelet therapy (for three to six months) followed by single antiplatelet therapy for life is also reasonable, as this regimen was used in the pivotal TAVI trials. (See "Transcatheter aortic valve implantation: Periprocedural and postprocedural management", section on 'Without concurrent indication for dual antiplatelet therapy'.)
CARDIOVASCULAR MEDICINE (September 2020)
Rhythm-control for high-risk, early atrial fibrillation
●For patients with newly diagnosed atrial fibrillation (AF) who are at high risk for cardiovascular complications and especially if the patient is symptomatic, we suggest a rhythm-control rather than a rate-control strategy, provided it can be initiated within 12 months of onset (Grade 2C).
Among patients with atrial fibrillation (AF), a survival benefit from a rhythm-control rather than a rate-control strategy has never been demonstrated. The EAST-AFNET 4 trial randomly assigned nearly 2800 patients with early AF (defined as AF diagnosed ≤12 months before enrollment) and at high risk for cardiovascular complications to early rhythm control with antiarrhythmic drugs or catheter ablation, or to usual care, which was a rate-control strategy for most patients . High risk was defined as age >75 years, prior transient ischemic attack or stroke, or meeting two of the following criteria: age >65 years, female sex, heart failure, hypertension, diabetes, severe coronary artery disease, chronic kidney disease, or left ventricular hypertrophy. After a median follow-up of 5.1 years, the group assigned to rhythm control had lower rates of death from cardiovascular causes (1.0 versus 1.3 percent) and stroke (0.6 versus 0.9 percent) compared with the group assigned to rate control. Based on these results, we now prefer early initiation of a rhythm-control strategy for most early AF patients meeting the criteria for high risk as defined in the trial. Previously, we preferred rate control for many of these patients, particularly if they were older and minimally symptomatic. (See "Rhythm control versus rate control in atrial fibrillation", section on 'EAST-AFNET 4'.)
INFECTIOUS DISEASES; OBSTETRICS, GYNECOLOGY AND WOMEN'S HEALTH (September 2020)
Health care workers at risk for human papillomavirus (HPV) exposure
●In addition to recommendations for routine HPV vaccination, we suggest HPV vaccination for health care workers who may be at risk for occupational exposure to HPV, even if they are older than 26 years (Grade 2C).
Smoke or vapor generated from ablative and excisional procedures (eg, loop electrosurgical excision procedure [LEEP]) for cervical intraepithelial neoplasia can expose health care workers to human papillomavirus (HPV) . This exposure may increase the risk of developing HPV-associated upper aerodigestive tract diseases such as oropharyngeal cancer and laryngeal papillomatosis. To decrease this risk, personal protection equipment (N-95 masks) and smoke evacuation systems should be used during these procedures. In addition, we agree with guidance from the American Society for Colposcopy and Cervical Pathology (ASCCP) and others that the entire operative team, including physicians, nurses, and operating room staff, receive the HPV vaccine, if not already vaccinated . (See "Cervical intraepithelial neoplasia: Diagnostic excisional procedures", section on 'Health care workers at risk for occupational exposure'.)
ONCOLOGY (June 2020)
Pembrolizumab versus first-line chemotherapy for mismatch repair-deficient metastatic colorectal cancer
Between 3 and 6 percent of metastatic colorectal cancers (mCRCs) are deficient in DNA mismatch repair (dMMR), for which potential benefit from immune checkpoint inhibitor immunotherapy has been shown after failure of initial systemic chemotherapy. Preliminary results from the KEYNOTE-177 trial suggest that first-line pembrolizumab offers better outcomes than first-line chemotherapy in this setting, with a doubling of progression-free survival, higher and more durable objective response rates, and fewer severe adverse effects . Overall survival data have not yet been presented. Based on these data, we now suggest first-line pembrolizumab monotherapy rather than systemic chemotherapy for patients with nonoperable dMMR mCRC. In June 2020, the US Food and Drug Administration (FDA) approved pembrolizumab for the first-line treatment of patients with unresectable or metastatic dMMR CRC. (See "Systemic therapy for nonoperable metastatic colorectal cancer: Selecting the initial therapeutic approach", section on 'Patients with DNA mismatch repair deficient/microsatellite unstable tumors'.)
INFECTIOUS DISEASES (March 2020, Modified April 2020)
One-time HCV screening for all adults ≥18 years
●We suggest one-time screening for hepatitis C virus infection in all adults aged ≥18 years rather than selective screening (Grade 2C).
In April 2020, the US Centers for Disease Control and Prevention (CDC) recommended that all adults ≥18 years be screened at least once for chronic hepatitis C virus (HCV) infection . The CDC recommendations differ from the US Preventive Services Task Force (USPSTF) recommendations issued in March 2020, which included an upper age limit of 79 years for universal screening . Previously, screening was recommended only for patients who had certain risk factors or were born during certain decades, but this approach results in many missed diagnoses. The improved efficacy, tolerability, and accessibility of antiviral treatment for HCV also support a broader screening strategy. We agree with the new CDC recommendation for broad one-time screening in all adults, and we continue to suggest repeat screening in individuals with ongoing risk factors (algorithm 1). (See "Screening and diagnosis of chronic hepatitis C virus infection", section on 'Routine one-time screening for adults'.)
ONCOLOGY (March 2020)
Hippocampal avoidance whole brain radiation for treatment of brain metastases
●For most patients undergoing whole brain radiation therapy (WBRT) for treatment of brain metastases, we suggest use of hippocampal avoidance intensity-modulated radiotherapy rather than conventional WBRT (Grade 2C). Patients with metastases within 5 mm of the hippocampi should receive conventional WBRT.
For patients receiving whole brain radiation (WBRT) for brain metastases, neurocognitive decline is a feared complication that adversely impacts quality of life. Lowering the dose of radiation delivered to the hippocampi with intensity-modulated radiation therapy (IMRT) has been suggested as a way to improve neurocognitive outcomes compared with conventional WBRT. In a randomized, unblinded trial in over 500 patients with brain metastases, the use of hippocampal avoidance IMRT (HA-IMRT) led to a 26 percent relative reduction in the risk of cognitive toxicity compared with conventional WBRT . Patients in the HA-IMRT group reported less difficulty remembering things, less difficulty speaking, and greater improvement in fatigue at six months. Rates of brain control and overall survival were similar between groups, although confidence intervals were wide. All patients also received memantine, an N-methyl-D-aspartate antagonist that was shown to reduce the risk of neurotoxicity in a previous trial. Based on these results, we now suggest HA-IMRT rather than conventional WBRT in most patients who require WBRT for treatment of brain metastases, and we administer memantine concurrently. (See "Delayed complications of cranial irradiation", section on 'Prevention'.)
HEMATOLOGY (February 2020)
Less chemoimmunotherapy for limited stage diffuse large B cell non-Hodgkin lymphoma (DLBCL) with no adverse features
●For patients with limited stage (stage I or II) diffuse large B cell non-Hodgkin lymphoma (DLBCL) with no adverse features, we suggest four cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) rather than six or more cycles of R-CHOP, radiation therapy (RT) alone, or combined modality therapy (R-CHOP plus RT) (Grade 2C).
Limited stage (stage I or II) diffuse large B cell non-Hodgkin lymphoma (DLBCL) without adverse risk factors (ie, no bulky disease, normal lactate dehydrogenase [LDH], ECOG performance status 0-1) has an excellent prognosis when treated with the current standard approaches of either six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or three cycles of R-CHOP followed by radiation therapy (RT). To determine if less chemoimmunotherapy could achieve comparable outcomes with less toxicity, almost 600 patients ≤60 years with stage I-II DLBCL and no adverse risk factors were randomly assigned to four versus six cycles of R-CHOP . With median follow-up greater than five years, there was less hematologic and non-hematologic toxicity with four cycles of R-CHOP, while three-year progression-free survival (PFS) and estimated five-year PFS and overall survival were similar compared with six cycles. We now suggest four cycles of R-CHOP for treatment of adults of any age with limited stage DLBCL and no adverse features. (See "Initial treatment of limited stage diffuse large B cell lymphoma", section on 'No adverse features'.)