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 (November 2020, Modified April 2021)
Vaccines to prevent SARS-CoV-2 infection
●For individuals who are eligible for vaccination according to local allocation priorities, we recommend COVID-19 vaccination (Grade 1B). Vaccine selection depends on local availability.
Various vaccines to prevent SARS-CoV-2 infection have become available in different countries. In the United States, the COVID-19 mRNA vaccines BNT162b2 (Pfizer-BioNTech COVID-19 vaccine) and mRNA 1273 (Moderna COVID-19 vaccine) and the COVID-19 adenovirus vector vaccine Ad26.COV2.S (Janssen COVID-19 vaccine) have received emergency use authorization [1-3]. The mRNA vaccines are each given as two intramuscular doses separated by a few weeks; the adenovirus vector vaccine is a single intramuscular dose. In large placebo-controlled trials, these vaccines were highly effective in preventing laboratory-confirmed COVID-19, especially severe/critical disease [4-6]. Local and systemic adverse effects (pain, fever, fatigue, headache) are common but usually nonsevere. Ad26.COV2.S is associated with an extremely small risk of thrombosis with thrombocytopenia, but its benefits outweigh this rare risk . (See "COVID-19: Vaccines to prevent SARS-CoV-2 infection".)
NEUROLOGY (April 2021)
Second course of IVIG not beneficial for patients with severe Guillain-Barré syndrome
●For patients with Guillain-Barré syndrome treated initially with IVIG who show further deterioration or no improvement, we suggest against retreating with IVIG because it exposes patients to adverse risks without additional benefit (Grade 2C).
For patients with severe Guillain-Barré syndrome (GBS) whose symptoms worsen or fail to improve after a course of intravenous immune globulin (IVIG), a repeat course has sometimes been given, despite uncertain benefit. In a randomized trial of 93 patients with GBS and a poor predicted outcome, those assigned to a second course of IVIG (given two to four days after completion of the first course) had similar disability but more adverse effects, including thromboembolic complications, than those who were assigned to placebo . Based on these data, we suggest against retreating with a second course of IVIG for patients with GBS. (See "Guillain-Barré syndrome in adults: Treatment and prognosis", section on 'Relapses'.)
ONCOLOGY (April 2021)
Postoperative nivolumab after initial chemoradiotherapy for esophageal and esophagogastric junction cancer
●For patients with localized esophageal or esophagogastric junction cancer who have residual disease in the surgical specimen after initial chemoradiotherapy, we suggest nivolumab for one year (Grade 2B), although we discontinue it if disease recurs during treatment.
Patients with localized esophageal or esophagogastric junction (EGJ) cancer who are treated with neoadjuvant chemoradiotherapy and have residual disease at the time of resection remain at high risk for recurrence and death from cancer, yet optimal postoperative management is unknown. In the CheckMate 577 trial of nearly 800 such patients, adjuvant nivolumab for up to one year doubled median disease-free survival compared with placebo (22.4 versus 11 months) without adversely affecting health-related quality of life . Benefits were seen across all patient subgroups (histology, location, initial and posttreatment disease stage) and did not depend on programmed cell death ligand-1 status. Overall survival data are not yet mature. Based on these results and the morbidity of disease recurrence, we now suggest one year of adjuvant nivolumab for patients with resected esophageal or EGJ cancer who have residual disease in the surgical specimen after initial chemoradiotherapy. (See "Radiation therapy, chemoradiotherapy, neoadjuvant approaches, and postoperative adjuvant therapy for localized cancers of the esophagus", section on 'After preoperative therapy'.)
INFECTIOUS DISEASES; EMERGENCY MEDICINE (ADULT AND PEDIATRIC) (February 2021)
Tocilizumab for COVID-19
●For hospitalized adults with COVID-19 who, within the prior 24 to 48 hours, have initiated high-flow supplemental oxygen, non-invasive ventilation, or mechanical ventilation, we suggest adding tocilizumab to usual care (which includes dexamethasone) (Grade 2C).
For hospitalized adults with COVID-19 who are receiving low-flow supplemental oxygen and have both progressively increasing oxygen requirements despite dexamethasone and significantly elevated inflammatory markers, we suggest adding tocilizumab to usual care (Grade 2C). However, if availability of tocilizumab is limited, we prioritize it for patients on higher levels of oxygen support.
Results from two recent open-label randomized trials of the interleukin-6 pathway inhibitor tocilizumab suggest a mortality benefit in severe COVID-19. In one of these trials, tocilizumab reduced 28-day mortality among over 4000 patients who were on oxygen support of any kind and had a C-reactive protein level ≥75 mg/L (29 versus 33 percent with usual care alone) . In the other, tocilizumab reduced in-hospital mortality among 800 patients who had started high-flow oxygen or more intensive respiratory support within the prior 24 hours (28 versus 36 percent with usual care alone) . These findings contrast with prior smaller trials, which had not identified a mortality benefit. Potential reasons for the difference include a higher baseline mortality and concomitant use of glucocorticoids in the more recent trials. Overall, tocilizumab does appear to have a clinical benefit, although optimal use remains uncertain. We suggest tocilizumab in addition to usual care for patients who recently initiated high-flow oxygen, noninvasive ventilation, or mechanical ventilation and for select patients on low-flow oxygen who are clinically progressing and have significantly elevated inflammatory markers. (See "COVID-19: Management in hospitalized adults", section on 'IL-6 pathway inhibitors (eg, tocilizumab)'.)
INFECTIOUS DISEASES; OBSTETRICS, GYNECOLOGY AND WOMEN'S HEALTH; PRIMARY CARE (ADULT); FAMILY MEDICINE AND GENERAL PRACTICE; EMERGENCY MEDICINE (ADULT AND PEDIATRIC) (January 2021)
Anaerobic coverage for treatment of pelvic inflammatory disease
Anaerobic bacteria are frequently recovered from the upper genital tract of women with acute pelvic inflammatory disease (PID), but whether antibiotic regimens for PID should include anaerobic coverage has been controversial. In a trial of 233 women with mild to moderate PID who were treated with ceftriaxone and doxycycline and randomly assigned to additionally receive either metronidazole (500 mg twice daily) or placebo for 14 days, clinical improvement rates at three days were similar in the two groups . However, at 30 days, women in the metronidazole group had a lower rate of pelvic tenderness (9 versus 20 percent) and a nonsignificant trend towards a higher 30-day clinical cure rate (96 versus 90 percent). Adherence was similar in both groups. Given the potential additional benefits of anaerobic coverage, we now add metronidazole to standard outpatient therapy for PID. (See "Pelvic inflammatory disease: Treatment in adults and adolescents", section on 'Anaerobic bacteria'.)
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 (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 [14,15]. 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 "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 deficient DNA mismatch repair/microsatellite unstable tumors'.)