Your activity: 50 p.v.
your limit has been reached. plz Donate us to allow your ip full access, Email: sshnevis@outlook.com

What's new in primary care

What's new in primary care
Authors:
Lisa Kunins, MD
Jane Givens, MD, MSCE
Literature review current through: Feb 2022. | This topic last updated: Feb 28, 2022.

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

IMMUNIZATIONS

Herpes zoster vaccination for immunocompromised adults ≥19 years old (October 2021, Modified February 2022)

Herpes zoster vaccination is indicated for those ≥50 years of age to reduce the risk of herpes zoster and postherpetic neuralgia. The United States Advisory Committee on Immunization Practices recently expanded the indication for the recombinant zoster vaccine (RZV) to include immunocompromised adults ≥19 years of age [1]; RZV has been shown to reduce the incidence of herpes zoster in immunocompromised adults. Vaccination should ideally be administered prior to immunosuppression, but when this is not possible, it should be administered during periods of lower immunosuppression and stable disease.

Booster doses of COVID-19 vaccines for individuals 12 years or older (October 2021, Modified February 2022)

Several countries have introduced booster doses of COVID-19 vaccines because of potentially attenuated vaccine effectiveness due to waning efficacy and variants. The US Food and Drug Administration has authorized and the Centers for Disease Control and Prevention (CDC) recommends a booster dose for all individuals 12 years or older [2-5]. The booster dose is given five months after a primary BNT162b2 (Pfizer) or mRNA-1273 (Moderna) series for most patients (or three months after the primary series for immunocompromised patients) and two months after a primary Ad26.COV2.S (Johnson & Johnson) series. Any vaccine authorized for the patient's age group can be used for the booster dose, regardless of the vaccine used for the primary series; in general, we favor one of the mRNA vaccines over Ad26.COV2.S. We recommend booster doses for eligible individuals, based on trials and observational evidence suggesting improved vaccine efficacy following a booster dose. (See "COVID-19: Vaccines", section on 'Role of booster vaccinations/waning efficacy'.)

Additional COVID-19 vaccine primary series dose for immunocompromised individuals (August 2021, Modified February 2022)

COVID-19 vaccines are less effective among patients with certain immunocompromising conditions than in the general population; additional vaccine doses have been associated with improved effectiveness in this population. We agree with recommendations from the Advisory Committee on Immunization Practices (ACIP) in the United States that individuals with such conditions (table 1) receive an additional mRNA vaccine dose as part of their primary COVID-19 vaccine series (eg, following two doses of an mRNA vaccine or one dose of Ad26.COV2.S vaccine) [6,7]. This additional primary series dose is distinct from the booster dose, which such patients should additionally receive, although at a shorter interval than recommended for the general population. (See "COVID-19: Vaccines", section on 'Immunocompromised individuals'.)

COVID-19 vaccination does not affect fertility (January 2022)

Possible cross-reactivity between antibodies to the SARS-CoV-2 virus's spike protein and a protein involved in embryo development raised concerns for impaired fertility following either viral infection or vaccination. In the largest retrospective cohort study comparing 222 vaccinated with 983 unvaccinated females undergoing in vitro fertilization (IVF) between February and September 2021, outcomes of ovarian stimulation and embryo transfer were similar for both groups, including similar fertilization and clinical pregnancy rates [8]. These data add to the body of evidence supporting lack of negative effects of vaccination on fertility or IVF cycles. (See "In vitro fertilization: Overview of clinical issues and questions", section on 'No proven effect'.)

Missed opportunities for influenza vaccination (January 2022)

Influenza vaccination rates remain suboptimal. In a retrospective study including more than 31 million Medicare beneficiaries >19 years of age in the United States during the 2018 to 2019 influenza season, vaccination claims were filed for only 50 percent of individuals [9]. Vaccination uptake was higher among White beneficiaries than Black or Hispanic beneficiaries (53, 35, and 30 percent, respectively), and was higher for those with high-risk conditions than for those without (56 versus 27 percent, respectively). Among unvaccinated beneficiaries overall, 77 percent visited a provider during influenza season. A comprehensive strategy leveraging all opportunities for vaccination is needed to improve influenza vaccine uptake. (See "Seasonal influenza vaccination in adults", section on 'Improving vaccination rates'.)

Evaluation and management of immediate allergic reactions to SARS-CoV-2 vaccines (November 2021)

An international panel of experts in allergy, infectious disease, and emergency medicine released recommendations for the evaluation and management of immediate allergic reactions to SARS-CoV-2 vaccines, based on a systematic review and meta-analysis [10]. These recommendations, which include not performing empiric testing in patients with past anaphylaxis to polyethylene glycol (PEG) or polysorbates, and referring patients who experienced anaphylaxis to the first dose of an mRNA vaccine to an allergist or completing vaccination with a different vaccine, are consistent with our approach. Most patients are able to complete the vaccination process. (See "COVID-19: Allergic reactions to SARS-CoV-2 vaccines", section on 'Immediate reactions to an initial dose'.)

Post-COVID-19 symptoms not affected by vaccination (October 2021)

Some patients with persistent symptoms following COVID-19 are concerned that vaccination could exacerbate them. A recent study of 163 patients who had a heavy burden of post-COVID-19 symptoms at eight months reported that most patients' symptoms had either improved or remained unchanged one month after receiving either the BNT162b2 (Pfizer) or ChAdOx1 nCoV-19/AZD1222 (AstraZeneca) vaccine [11]. We continue to recommend vaccination in patients following COVID-19, regardless of the presence of persistent symptoms. (See "COVID-19: Vaccines", section on 'History of SARS-CoV-2 infection' and "COVID-19: Evaluation and management of adults following acute viral illness", section on 'Persistent symptoms'.)

Updated ACIP guidance on influenza vaccination in the United States (September 2021)

In August 2021, the United States Advisory Committee on Immunization Practices (ACIP) issued recommendations for prevention of seasonal influenza [12]. During the 2021-22 influenza season, the following vaccine types are expected to be available: inactivated influenza vaccines (IIV4s), recombinant influenza vaccine (RIV4), and live attenuated influenza vaccine (LAIV4) (table 2 and table 3); all vaccines are expected to be quadrivalent. For the IIV4s produced from cell culture, the approved age indication has been expanded from ≥4 years to ≥6 months of age [13,14]. Influenza vaccination may be co-administered with COVID-19 vaccination, at different anatomic sites. We agree with the ACIP guidance. (See "Seasonal influenza vaccination in adults", section on 'Available formulations' and "Seasonal influenza in children: Prevention with vaccines", section on 'Influenza vaccines'.)

GENERAL INTERNAL MEDICINE

Choosing apixaban or rivaroxaban for venous thromboembolism (December 2021)

Although several direct oral anticoagulants (DOACs) are available for treating patients with venous thromboembolism (VTE), no randomized trials support choosing one over another. A recent retrospective study reported that among 37,000 new users of apixaban or rivaroxaban, apixaban was associated with lower rates of recurrent VTE (hazard ratio [HR] 0.77, 95% CI 0.69-0.87) and bleeding (HR 0.60, 95% CI 0.53-0.69) [15]. While these data favor apixaban, we continue to favor an individualized choice among DOACs that also take into consideration cost, availability, and preference for once- versus twice-daily dosing. (See "Venous thromboembolism: Anticoagulation after initial management", section on 'Efficacy' and "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects".)

Patient education reduces hospital readmissions (September 2021)

Many hospital readmissions are felt to be avoidable; however, interventions to reduce them are often multifaceted and unsuccessful. In a 2021 meta-analysis of 19 trials from seven countries, patients assigned to receive a communication intervention at hospital discharge, such as medication counseling or disease-specific education, had lower 30-day readmission rates than those assigned to usual care [16]. Focused patient communication and education at discharge may be a relatively simple way to help prevent unnecessary readmissions. (See "Hospital discharge and readmission", section on 'Patient education'.)

Acupuncture for chronic prostatitis and chronic pelvic pain (September 2021)

Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) can be difficult to treat. Acupuncture may be of interest to some patients but is not well studied. In an eight-week trial among 440 males with moderate to severe CP/CPPS, those receiving acupuncture treatment had a greater reduction in symptoms at 8 and 32 weeks than those receiving sham treatment [17]. Although we typically suggest pharmacologic therapy including alpha blockade and anti-inflammatories for CP/CPPS, acupuncture is a reasonable alternative or adjunct treatment option. (See "Chronic prostatitis and chronic pelvic pain syndrome", section on 'Nonpharmacologic therapies'.)

PRIMARY CARE ALLERGY AND IMMUNOLOGY

Identifying patients at high risk for true beta-lactam allergy (November 2021)

Allergy to penicillin is the most common drug allergy, but the majority of patients with this label are not actually allergic. In a retrospective study of 410 adults referred to drug allergy centers specifically for urticarial eruptions occurring in association with a beta-lactam antibiotic, three questions proved useful for identifying patients at high risk for true allergy [18]:

Did the urticaria develop after the first dose (ie, dose 1) (versus after subsequent doses)?

Did the urticaria develop within 1 hour of the inciting dose?

Did the urticaria resolve within 1 day of stopping the beta-lactam in question?

Patients answering yes to all three questions (named the 1-1-1 criterion by the investigators) had a high risk of a positive allergy evaluation (PPV = 90 percent). Such patients should not be re-exposed to beta-lactams and should be referred to an allergy specialist if future beta-lactam use is deemed medically important. (See "Penicillin allergy: Immediate reactions", section on 'Historical features that predict true allergy'.)

PRIMARY CARE ENDOCRINOLOGY AND DIABETES

Combination T4 and T3 therapy versus T4 alone for primary hypothyroidism (February 2022)

Some hypothyroid patients remain symptomatic after T4 replacement normalizes thyroid stimulating hormone. In a crossover trial evaluating T4 alone, combined T4 and T3, or desiccated thyroid extract in 75 hypothyroid patients previously treated with a stable dose of T4, there was no difference among the three groups in patient preference or scores on the thyroid symptom or general health questionnaires [19]. However, the 20 patients with the most symptoms at baseline had a strong preference for combination therapy or thyroid extract over T4 alone and had significant improvement in the scores. Analysis of this subgroup did not reveal any significant differences in etiology of hypothyroidism, serum thyroid tests while taking T4, or presence of polymorphisms in the deiodinase 2 gene. Although we do not suggest the routine use of combined T4 and T3, selected patients may benefit from a trial of the combination, using doses of T4 and T3 that mimic normal physiology. (See "Treatment of primary hypothyroidism in adults", section on 'Is there a role for T3?'.)

Semaglutide for obesity treatment in adults (January 2022)

The glucagon-like peptide-1 (GLP-1) receptor agonists liraglutide and semaglutide are approved for the treatment of obesity. In the STEP 8 trial, participants were assigned to receive once-weekly subcutaneous semaglutide or once-daily subcutaneous liraglutide for 68 weeks; all participants received counseling on lifestyle modification [20]. Those in the semaglutide group lost a greater percentage of body weight than those receiving liraglutide (-15.8 versus -6.4 percent). For patients who are overweight or with obesity and in whom pharmacologic therapy is warranted, we suggest using a GLP-1 receptor agonist; we prefer treatment with semaglutide since administration is once weekly and it has greater efficacy than liraglutide. (See "Obesity in adults: Drug therapy", section on 'Efficacy'.)

Diabetes drugs and cardiovascular outcomes in at-risk adults (November 2021)

In a meta-analysis of trials comparing a GLP-1 receptor agonist (eg, liraglutide, semaglutide), SGLT2 inhibitor (eg, dapagliflozin, empagliflozin), or DPP-4 inhibitor (eg, linagliptin, sitagliptin) with placebo in people with type 2 diabetes and established cardiovascular disease (CVD), GLP-1 receptor agonists and SGLT2 inhibitors reduced the risk of all-cause and cardiovascular mortality [21]. GLP-1 receptor agonists also reduced the risk of fatal or non-fatal stroke, whereas SGLT2 inhibitors reduced the risk of heart failure hospitalizations. DPP-4 inhibitors did not reduce or increase any CVD outcomes. For patients with type 2 diabetes who are not achieving glycemic goals with metformin and in whom atherosclerotic CVD predominates, we typically add a GLP-1 receptor agonist to metformin. For similar patients in whom heart failure predominates, we typically add an SGLT2 inhibitor. (See "Sodium-glucose co-transporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Glucagon-like peptide 1 receptor agonists for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects'.)

Defining subclinical hypothyroidism in older adults (October 2021)

There is disagreement about the appropriate upper limit of normal for serum thyroid stimulating hormone (TSH) in older adults. Although there is an age-related shift toward higher TSH concentrations in older adults, age-based normal ranges for TSH are not widely implemented. In one study of over 2000 adults >70 years of age, the likelihood of a diagnosis of subclinical hypothyroidism (defined as an elevated TSH with a normal free T4) decreased from 29 to 3 percent if age-specific rather than uniform normal reference ranges were used [22]. We suggest not treating older adults for subclinical hypothyroidism for a TSH above the upper limit of normal up to and including 6.9 mU/L, since TSH values in the range are age appropriate. (See "Subclinical hypothyroidism in nonpregnant adults", section on 'Epidemiology'.)

PRIMARY CARE GERIATRICS

Avoiding delay in indicated cataract surgery (November 2021)

Although many patients with cataracts are older adults with comorbidities, few conditions preclude proceeding with indicated cataract surgery for those who can tolerate the required positioning because no blood loss or fluid shifts occur. Moreover, significant delays (ie, more than four months) for cataract surgery have been associated with increased morbidity due to greater likelihood of falls, automobile accidents, and worsening cognitive impairment. We agree with the new Society for Ambulatory Anesthesia position statement that recommends against postponing cataract surgery unless the patient has an acute condition that requires time to achieve optimal medical management [23]. (See "Anesthesia for elective eye surgery", section on 'Anesthetic considerations'.)

PRIMARY CARE GYNECOLOGY

Lack of impact of assisted reproductive technology on offspring depressive disorders (February 2022)

Increasing use of assisted reproductive technology (ART), including in vitro fertilization and intracytoplasmic sperm injection, has raised questions about the technology's possible impact on offspring mental health. In the largest study to date, including over 1.2 million individuals aged 12 to 25 years followed for a median of 18 years, the risks of depression, anxiety, or suicide were similar for those conceived with ART compared with all others in adjusted analysis [24]. Although the study used billing codes as proxy for clinical diagnoses, the results are consistent with prior studies and reassuring that use of ART does not increase the risk of depressive disorders in offspring. (See "Assisted reproductive technology: Infant and child outcomes", section on 'General health'.)

Updated guidelines for cervical cancer screening in patients with HIV (August 2021)

In August 2021, the United States Department of Health and Human Services along with the National Institutes of Health published updated guidelines for the screening of cervical cancer in patients with HIV. In contrast to the previous guideline, cervical cancer screening at the time of HIV diagnosis is now limited to patients age 21 years or older [25]. We also follow these updated guidelines for patients without HIV who are on long-term immunosuppressive therapy (eg, solid organ transplant, allogeneic hematopoietic stem cell transplant, systemic lupus erythematous, and those with inflammatory bowel disease or rheumatologic disease requiring current immunosuppressive treatments). (See "Screening for cervical cancer in patients with HIV infection and other immunocompromised states", section on 'Initial screening' and "Screening for cervical cancer in patients with HIV infection and other immunocompromised states", section on 'HIV-negative immunosuppressed patients'.)

PRIMARY CARE HEMATOLOGY AND ONCOLOGY

ITP after COVID-19 vaccination (January 2022)

Exacerbations of immune thrombocytopenia (ITP) as well as new-onset ITP have been reported after COVID-19 vaccination [26,27]. Individuals with ITP who receive any COVID-19 vaccine should be advised about this risk, and platelet counts should be monitored before and after vaccination. The benefits of vaccination outweigh the risks in almost all patients with ITP. Those in the midst of a flare can delay vaccination until the flare is controlled; flares that occur following vaccination tend to be transient and respond well to standard ITP therapy. ITP is distinct from the exceedingly rare syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT). (See "Initial treatment of immune thrombocytopenia (ITP) in adults", section on 'COVID-19 vaccination'.)

Safety of anticoagulation in factor XI deficiency (November 2021)

Factor XI deficiency is a bleeding disorder in which bleeding typically occurs with trauma but not spontaneously. Although factor XI deficiency provides partial protection from venous thromboembolism, antithrombotic therapy may be indicated in selected individuals (eg, if they develop atrial fibrillation [AF]). A new review of over 200 people with factor XI deficiency identified 15 individuals who were treated with anticoagulation, mostly with warfarin for AF [28]. There were no major bleeding events. Two patients had minor bleeds before starting warfarin, and two had minor bleeds after starting warfarin, suggesting no significant increase in bleeding. These findings are reassuring regarding the safety of anticoagulation when needed. (See "Factor XI (eleven) deficiency", section on 'Anticoagulation or antiplatelet therapy'.)

Risk of GI bleeding with DOACs (October 2021)

Direct oral anticoagulants (DOACs) are generally preferred over warfarin in individuals with non-valvular atrial fibrillation or venous thromboembolism. A new study evaluated the risk of gastrointestinal (GI) bleeding in over 5000 individuals taking apixaban, rivaroxaban, or dabigatran [29]. Higher rates of GI bleeding were seen in individuals taking rivaroxaban (3.2 per 100 patient-years) than with the other agents (2.5 for apixaban and 1.9 for dabigatran). The once-daily dosing of rivaroxaban and higher peak levels may explain the higher bleeding risk; the other agents are dosed twice daily. These results may be a consideration when choosing among DOACs. (See "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects", section on 'Differences between factor Xa inhibitors'.)

Thromboprophylaxis does not improve outcomes in outpatients with COVID-19 (October 2021)

While prophylaxis for venous thromboembolism (VTE) is used routinely in individuals hospitalized with COVID-19, the role of thromboprophylaxis in outpatients has been unclear. A new randomized trial, ACTIV-4B, evaluated outcomes in 657 symptomatic outpatients with COVID-19 who were treated for 45 days with aspirin, prophylactic-dose apixaban, therapeutic-dose apixaban, or placebo [30]. There was no statistically significant difference in mortality, VTE, or arterial thromboembolism, with very low numbers in all groups. As expected, bleeding complications were higher with apixaban and aspirin. These results support our practice of not routinely using anticoagulation or aspirin in outpatients with COVID-19. Outpatient thromboprophylaxis may be appropriate in selected individuals with especially high thrombotic risk; if thromboprophylaxis is used, an oral anticoagulant is preferred over aspirin. (See "COVID-19: Hypercoagulability", section on 'Aspirin/antiplatelet agents'.)

PRIMARY CARE INFECTIOUS DISEASES

Treatment of COVID-19 in outpatients at risk for severe disease (November 2021, Modified February 2022)

Nirmatrelvir-ritonavir, the monoclonal antibody sotrovimab, remdesivir, and high-titer convalescent plasma have all been shown to reduce the risk of hospitalization when given early in the course of COVID-19 [31-34]. For outpatient adults who have mild-to-moderate COVID-19 and are at risk for progression to severe disease (table 4), we recommend treatment with either nirmatrelvir-ritonavir or sotrovimab. When these are not available, we consider remdesivir and convalescent plasma, which may be complicated to administer, as alternatives. If none are feasible options, molnupiravir is an alternative, but it may be less effective and potentially teratogenic [35]. Bebtelovimab is an alternative monoclonal antibody that is active against Omicron, but there are limited data to support its use [36]. When supplies are limited, these treatments should be prioritized for immunocompromised individuals expected to have a suboptimal vaccine response and unvaccinated or incompletely vaccinated individuals at highest risk for severe disease (table 5) [37]. (See "COVID-19: Outpatient evaluation and management of acute illness in adults".)

COVID-19: Updated CDC recommendations for isolation and quarantine in the community (January 2022)

In December 2021, the United States Centers for Disease Control and Prevention (CDC) updated recommendations on home isolation for individuals with SARS-CoV-2 infection and post-exposure precautions in the community [38]. For select immunocompetent patients with infection (eg, those who are asymptomatic; those with mild, improving infection), the duration of isolation was reduced from 10 to 5 days, followed by strict mask-wearing when around others for another 5 days. Following exposure, people should monitor for symptoms and wear masks when around others for 10 days; those not up-to-date on vaccination should quarantine at home for the first 5 days. Additional details on the role of testing and other restrictions during the post-infection or post-exposure period, as well as updated recommendations for quarantine and isolation for healthcare personnel can be found on the CDC website. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Testing and quarantine' and "COVID-19: Infection prevention for persons with SARS-CoV-2 infection", section on 'In the community setting'.)

New naming convention for therapeutic monoclonal antibodies (January 2022)

The number of therapeutic monoclonal antibodies (mAbs) continues to increase. In order to reduce sound-alikes and specify structural components of the immunoglobulins, the World Health Organization International Nonproprietary Names (INN) Programme has developed four new suffixes to be used instead of "mab" for antibodies developed from 2022 onward [39]. Unmodified immunoglobulins will end in "tug"; mAbs with an engineered constant region will end in "bart"; bifunctional mAbs will end in "mig"; and variable region fragments will end in "ment." (See "Overview of therapeutic monoclonal antibodies", section on 'Naming convention for therapeutic mAbs'.)

CDC definition of post-acute COVID-19 (October 2021)

The Centers for Disease Control and Prevention (CDC) recently updated their definition of post-acute sequelae of SARS-CoV-2 infection (PASC; "long-COVID") [40]. While it was previously defined as "patients with a broad range of symptoms (physical and mental) that develop during or after COVID-19, continue for ≥4 weeks, and are not explained by an alternate diagnosis," the CDC further specified the duration of symptoms to include only those with symptoms for ≥2 months (ie, 3 months from the onset). (See "COVID-19: Evaluation and management of adults following acute viral illness", section on 'Terminology and stages of recovery'.)

Updated sexually transmitted infections guidelines from CDC (October 2021)

In 2021, the United States Centers for Disease Control and Prevention (CDC) updated its guidelines on management of sexually transmitted infections [41]. Important changes include preferences for doxycycline over azithromycin for Chlamydia trachomatis infections and nongonococcal urethritis, routine anaerobic coverage for pelvic inflammatory disease, and a moxifloxacin-based regimen for Mycoplasma genitalium. The guidelines also affirmed previous recommendations to use a 500 mg dose of intramuscular ceftriaxone for gonococcal infections. Our approaches to sexually transmitted infections are largely consistent with these updated guidelines. (See "Pelvic inflammatory disease: Treatment in adults and adolescents" and "Mycoplasma genitalium infection in males and females" and "Treatment of uncomplicated Neisseria gonorrhoeae infections" and "Treatment of Chlamydia trachomatis infection", section on 'Doxycycline as preferred agent'.)

PRIMARY CARE NEPHROLOGY AND HYPERTENSION

Effect of a salt substitute on cardiovascular events and mortality (September 2021)

Strong evidence supports that dietary sodium reduction can lower blood pressure, but few trials have directly assessed the effects of sodium reduction on long-term cardiovascular outcomes and mortality. In the recent Salt Substitute and Stroke Study (SSaSS), which randomly assigned over 20,000 older adults at high cardiovascular risk to use a potassium-enriched salt substitute at home or to continue using regular salt, those assigned to the reduced sodium intervention had a lower risk of stroke and all-cause mortality at five years [42]. These findings support our recommendation to reduce dietary sodium intake. (See "Salt intake, salt restriction, and primary (essential) hypertension", section on 'Effects of sodium on cardiovascular disease'.)

PRIMARY CARE NEUROLOGY

Updated guidelines for management of restless legs syndrome (October 2021)

Updated consensus-based guidelines for the management of restless legs syndrome (RLS) have been published by the RLS Foundation [43]. For chronic persistent RLS in adults despite appropriate iron supplementation, the guideline suggests first-line therapy with an alpha-2-delta calcium channel ligand (gabapentin, gabapentin enacarbil, or pregabalin), except when certain comorbidities are present (eg, obesity, moderate to severe depression, gait instability, respiratory disease, or a history of substance use disorder). In such cases, a non-ergot dopamine agonist (pramipexole, ropinirole, rotigotine) is preferred initially, with monitoring for complications such as augmentation and impulse control disorders. Our approach is consistent with these guidelines (algorithm 1). (See "Management of restless legs syndrome and periodic limb movement disorder in adults", section on 'Choice of therapy'.)

Oral atogepant for episodic migraine prevention (October 2021)

Small-molecule calcitonin gene-related peptide (CGRP) antagonists ("gepants") are orally administered medications formulated typically for the acute treatment of migraine. The effectiveness of a novel agent, atogepant, was evaluated in a preventive trial in 873 patients with migraine. After 12 weeks, patients assigned to atogepant had fewer migraine days per month than those assigned to placebo and were also likelier to achieve at least 50 percent reduction in the three-month mean number of monthly migraine days (58 versus 29 percent) [44]. These data support the addition of oral atogepant as an effective agent for the prevention of episodic migraine. (See "Preventive treatment of episodic migraine in adults", section on 'CGRP antagonists'.)

Palliative care and hospice referral guidance in Parkinson disease (September 2021)

In patients with advanced Parkinson disease (PD), it can be difficult to determine the most appropriate timing for hospice referral, and there are no validated end-of-life prognostic tools. A working group sponsored by the Parkinson's Foundation has proposed guidance to identify patients who would likely benefit from hospice/palliative care [45]. Referral should be considered in patients with critical nutrition impairment, life-threatening complications, or poorly responsive motor symptoms causing impaired self care in the prior year; rapid or accelerating motor or nonmotor disease progression and disability; or advanced dementia meeting hospice referral criteria based on Medicare eligibility guidelines or other prognostic tools. (See "Palliative approach to Parkinson disease and parkinsonian disorders", section on 'Life expectancy and hospice eligibility'.)

Carotid stenting versus endarterectomy for asymptomatic carotid stenosis (September 2021)

Earlier trials comparing transfemoral carotid artery stenting (TF-CAS) with carotid endarterectomy (CEA) for asymptomatic carotid stenosis reported that the periprocedural (30-day) stroke or death rate is higher for TF-CAS, while long-term outcomes are similar. In the recent ACST-2 trial, the periprocedural rate of death or any stroke was slightly higher with TF-CAS compared with CEA, but the difference was not statistically significant [46]. This result largely reflected a higher incidence of nondisabling stroke in the TF-CAS group. The five-year rate of periprocedural death or any fatal or disabling stroke was similar for TF-CAS and CEA (3.3 versus 3.5 percent). For medically stable individuals with asymptomatic carotid stenosis of 70 to 99 percent, we advise a shared decision-making approach; either intensive medical therapy alone or intensive medical therapy plus revascularization with CEA are reasonable treatment options. For those with an unacceptably high surgical risk with suitable anatomy, carotid artery stenting is an alternative. (See "Management of asymptomatic extracranial carotid atherosclerotic disease", section on 'Stenting versus endarterectomy trials'.)

Clinical use of pimavanserin in patients with neurodegenerative dementias (September 2021)

Pimavanserin is a newer antipsychotic agent that has been approved in the United States (US) since 2016 for treatment of psychosis in patients with Parkinson disease (PD). Two new reports expand information on both efficacy and potential risks in patients with neurodegenerative diseases:

In a randomized discontinuation trial of pimavanserin in 351 patients with dementia-related psychosis, among those who responded initially to treatment, relapses were approximately half as common in patients assigned to continued pimavanserin compared with placebo [47].

In a retrospective cohort study of >20,000 older adults with PD living in long-term care facilities in the US, pimavanserin use, compared with nonuse, was associated with an increased adjusted risk of 30-day hospitalization and mortality at multiple time points [48]. Residual confounding is possible, although other studies have raised similar safety concerns for antipsychotic agents as a class.

Like other antipsychotic agents, pimavanserin should be used selectively in patients with dementia and/or PD after discussing potential risks and benefits of treatment, alternative therapies for psychosis (algorithm 2 and algorithm 3), and risks related to ongoing symptoms. (See "Management of nonmotor symptoms in Parkinson disease", section on 'Refractory psychotic symptoms' and "Management of neuropsychiatric symptoms of dementia", section on 'Antipsychotic drugs'.)

PRIMARY CARE ORTHOPEDICS AND SPORTS MEDICINE

Myocarditis in athletes recovering from COVID-19 (October 2021)

Despite initial concerns about possible myocarditis in older adolescent and young adult athletes recovering from COVID-19, recent studies suggest that the risk of cardiac injury is low. In a prospective, multi-center cohort of over 3,000 US collegiate athletes diagnosed with COVID-19 and undergoing cardiac evaluation, possible cardiac injury was noted in 21 (0.7 percent), including 15 of 119 individuals who underwent cardiac magnetic resonance (CMR) imaging based on preliminary test findings (ECG, cardiac troponin, and/or echocardiography) and 6 of 198 individuals who underwent primary CMR screening [49]. During subsequent surveillance, only one adverse cardiac event occurred, most likely unrelated to COVID-19. These findings may not reflect the frequency of myocarditis after SARS-CoV-2 infection caused by subsequent variants such as the Delta variant. Nevertheless, they provide support for the current approach to cardiac evaluation and return to play in this population (algorithm 4). (See "COVID-19: Return to play or strenuous activity following infection", section on 'Cardiovascular complications in athletes'.)

PRIMARY CARE PULMONOLOGY

Long-term bleeding rates with direct oral anticoagulants (September 2021)

For patients with unprovoked venous thromboembolism (VTE), accurate information about bleeding rates are needed to inform decision-making. A recent meta-analysis of 27 studies (including 14 randomized trials) and >17,000 adults with unprovoked VTE reported a lower rate of bleeding among those receiving direct oral anticoagulants (DOACs) compared with patients receiving warfarin (1.12 versus 1.74 events per 100 person-years) [50]. Rates of bleeding were highest among patients >65 years of age and those with a creatinine clearance <50 mL/min, a history of bleeding, concomitant use of antiplatelet therapy, or a hemoglobin level <10 mg/L. These findings support our suggested choice of a DOAC rather than warfarin for most patients in whom indefinite anticoagulant therapy is indicated. (See "Selecting adult patients with lower extremity deep venous thrombosis and pulmonary embolism for indefinite anticoagulation", section on 'Baseline risk'.)

PRIMARY CARE PSYCHIATRY

Maintenance therapy of unipolar depression (December 2021)

The effectiveness and choice of maintenance therapy after recovery from unipolar depression are unclear. A recent trial enrolled 478 primary care patients who recovered from their most recent depressive episode with second-generation antidepressant drug therapy, continued taking the drug for at least nine months, and felt well enough to discontinue treatment [51]. In this double-blind trial, patients were randomly assigned to antidepressant maintenance or taper-and-discontinuation (with placebo substitution) over two months. Maintenance resulted in a lower rate of recurrence (39 versus 56 percent) and fewer anxiety and withdrawal symptoms; side effects were similar in the two groups. For patients who recover from an acute episode of depression, we recommend maintenance treatment. (See "Unipolar depression in adults: Continuation and maintenance treatment", section on 'Compared with placebo'.)

PRIMARY CARE RHEUMATOLOGY

Rapidly destructive hip disease after intraarticular glucocorticoid injection (January 2022)

Intraarticular glucocorticoid injections are sometimes used for symptom management for hip osteoarthritis (OA), but there is a concern that intraarticular glucocorticoids can also accelerate joint degeneration. In a case-control study comparing 40 patients with rapidly destructive hip disease (RDHD) and 717 controls who underwent total hip arthroplasty for OA, at least one intraarticular glucocorticoid injection was associated with a higher risk of RDHD (odds ratio 8.6) [52]. A dose-response effect was also observed, in which the risk of RDHD was higher with increasing doses of glucocorticoids as well as with the number of injections received. These findings support our approach of avoiding routine use of intraarticular glucocorticoid injections for patients with hip OA. (See "Management of hip osteoarthritis", section on 'Limited role of intraarticular glucocorticoids'.)

Lack of benefit for platelet-rich plasma injections for ankle osteoarthritis (November 2021)

Injection of intra-articular platelet-rich plasma (PRP) has been a therapeutic agent of interest for the management of osteoarthritis (OA), although most studies have evaluated knee OA symptoms. The first randomized trial to evaluate its use in ankle OA included 100 patients and found that intra-articular PRP injections, compared with placebo injections, did not improve a composite score of pain and function during the 26-week follow-up period [53]. These findings do not support the use of PRP injections for patients with ankle OA. (See "Investigational approaches to the management of osteoarthritis", section on 'Platelet-rich plasma'.)

Updated guidance for COVID-19 vaccine use in patients with rheumatic disease (September 2021)

The American College of Rheumatology (ACR) COVID-19 Vaccine Clinical Guidance Task Force has updated their recommendations regarding use of COVID-19 vaccines in patients with rheumatic disease [54]. These now emphasize that a third dose of either of the mRNA vaccines is appropriate for most patients with systemic rheumatic diseases. The ACR also noted a preference for a mRNA vaccine for patients not yet vaccinated, based on the potential benefits and regulatory approval of a three-dose series. The guidance addresses the timing of the vaccination, administration of immunosuppressive agents, and the use of postexposure prophylaxis with monoclonal antibodies in certain patients. (See "COVID-19: Care of adult patients with systemic rheumatic disease", section on 'Timing of vaccine'.)

OTHER ADULT PRIMARY CARE

Dental problems associated with oral dissolving buprenorphine (January 2022)

There are >300 reports of dental problems associated with use of buprenorphine formulations dissolved in the mouth, including the buccal formulation and sublingual tablets [55,56]. Reported problems include dental caries, abscesses, and damaged teeth, many of which have required tooth removal. The incidence of dental problems with buprenorphine is unknown. Patients who use orally dissolving buprenorphine should swish and swallow water after the drug has dissolved, see a dentist soon after starting the drug, and make sure the dentist knows they are taking the drug. The US Food and Drug Administration (FDA) has issued a related safety advisory and will mandate a label change. (See "Use of opioids in the management of chronic non-cancer pain", section on 'Buprenorphine for chronic pain'.)

Impact of cannabis use on pregnancy outcomes (January 2022)

As cannabis use continues to increase, more information regarding its impact on pregnancy outcomes has become available. A retrospective cohort study of over 32,500 pregnant individuals reported that prenatal cannabis use was associated with an approximately 30 percent increase in risk of low birth weight and small for gestational age infants compared with non-use [57]. The study controlled for cigarette use, but ascertainment of cannabis use by self-report was a limitation. We and several medical societies continue to advise against cannabis use in pregnancy because of potential adverse pregnancy and childhood neurodevelopmental outcomes. (See "Substance use during pregnancy: Overview of selected drugs", section on 'Obstetric outcomes'.)

Clinical use of whole genome sequencing (November 2021)

Sequencing the entire genome is expensive, time consuming, and often unnecessary. However, genome sequencing can be highly impactful for a subset of individuals with rare syndromes that defy a specific diagnosis. This was illustrated in a recent study from the 100,000 genomes project, in which whole genomes were sequenced in over 2000 patients (mostly adults) with undiagnosed conditions and over 2000 family members [58]. Neurologic, ophthalmologic, and tumor syndromes were highly represented. A genetic diagnosis was made in one-fourth, with various benefits reported including ending a diagnostic odyssey, identifying new targets for research, and facilitating testing of first-degree relatives. (See "Next-generation DNA sequencing (NGS): Principles and clinical applications", section on 'Risks and benefits'.)

Pandemic impacts cannabis use during pregnancy (October 2021)

Increased stress experienced during the COVID-19 pandemic caused many people to increase their use of cannabis, including pregnant individuals. A northern California health care system that performs universal toxicology testing in early pregnancy reported a 25 percent increase in maternal cannabis use during the first eight months of the pandemic compared with the 15 months prior (absolute use increased from 6.8 to 8.1 percent) [59]. This increase is concerning because approximately 50 percent of female marijuana users continue use across gestation. We advise pregnant individuals to avoid marijuana use because of concerns over fetal neurodevelopment. (See "Substance use during pregnancy: Overview of selected drugs", section on 'Prevalence of use'.)

REFERENCES

  1. Anderson TC, Masters NB, Guo A, et al. Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged ≥19 Years: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022. MMWR Morb Mortal Wkly Rep 2022; 71:80.
  2. Emergency Use Authorization (EUA) of the Pfizer-BioNTech COVID-19 Vaccine to Prevent Coronavirus. Fact sheet for healthcare providers administering vaccine. https://www.fda.gov/media/144413/download (Accessed on December 09, 2021).
  3. Emergency Use Authorization (EUA) of the Moderna COVID-19 Vaccine to prevent Coronavirus Disease 2019 (COVID-19). Factsheet for healthcare providers administering vaccine. https://www.fda.gov/media/144637/download?utm_medium=email&utm_source=govdelivery (Accessed on November 20, 2021).
  4. US Food and Drug Administration. Emergency use authorization (EUA) of the Janssen COVID-19 vaccine to prevent coronavirus disease 2019 (COVID-19). https://www.fda.gov/media/146304/download (Accessed on February 03, 2022).
  5. CDC Expands Eligibility for COVID-19 Booster Shots to All Adults https://www.cdc.gov/media/releases/2021/s1119-booster-shots.html (Accessed on November 20, 2021).
  6. CDC - An Additional Dose of mRNA COVID-19 Vaccine Following a Primary Series in Immunocompromised People. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-08-13/02-COVID-Dooling-508.pdf (Accessed on August 14, 2021).
  7. Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Authorized in the United States. https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html (Accessed on February 24, 2022).
  8. Aharon D, Lederman M, Ghofranian A, et al. In Vitro Fertilization and Early Pregnancy Outcomes After Coronavirus Disease 2019 (COVID-19) Vaccination. Obstet Gynecol 2022.
  9. Cho BH, Weinbaum C, Tsai Y, Koppaka R. Influenza Vaccine Uptake and Missed Opportunities Among the Medicare-Covered Population With High-Risk Conditions During the 2018 to 2019 Influenza Season : A Retrospective Cohort Study. Ann Intern Med 2022; 175:1.
  10. Greenhawt M, Abrams EM, Shaker M, et al. The Risk of Allergic Reaction to SARS-CoV-2 Vaccines and Recommended Evaluation and Management: A Systematic Review, Meta-Analysis, GRADE Assessment, and International Consensus Approach. J Allergy Clin Immunol Pract 2021; 9:3546.
  11. Arnold DT, Milne A, Samms E, et al. Symptoms After COVID-19 Vaccination in Patients With Persistent Symptoms After Acute Infection: A Case Series. Ann Intern Med 2021; 174:1334.
  12. Grohskopf LA, Alyanak E, Ferdinands JM, et al. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021-22 Influenza Season. MMWR Recomm Rep 2021; 70:1.
  13. Nolan T, Fortanier AC, Leav B, et al. Efficacy of a Cell-Culture-Derived Quadrivalent Influenza Vaccine in Children. N Engl J Med 2021; 385:1485.
  14. US Food and Drug Administration. Flucelvax quadrivalent. https://www.fda.gov/vaccines-blood-biologics/vaccines/flucelvax-quadrivalent (Accessed on October 18, 2021).
  15. Dawwas GK, Leonard CE, Lewis JD, Cuker A. Risk for Recurrent Venous Thromboembolism and Bleeding With Apixaban Compared With Rivaroxaban: An Analysis of Real-World Data. Ann Intern Med 2022; 175:20.
  16. Becker C, Zumbrunn S, Beck K, et al. Interventions to Improve Communication at Hospital Discharge and Rates of Readmission: A Systematic Review and Meta-analysis. JAMA Netw Open 2021; 4:e2119346.
  17. Sun Y, Liu Y, Liu B, et al. Efficacy of Acupuncture for Chronic Prostatitis/Chronic Pelvic Pain Syndrome : A Randomized Trial. Ann Intern Med 2021; 174:1357.
  18. Sabato V, Gaeta F, Valluzzi RL, et al. Urticaria: The 1-1-1 Criterion for Optimized Risk Stratification in β-Lactam Allergy Delabeling. J Allergy Clin Immunol Pract 2021; 9:3697.
  19. Shakir MKM, Brooks DI, McAninch EA, et al. Comparative Effectiveness of Levothyroxine, Desiccated Thyroid Extract, and Levothyroxine+Liothyronine in Hypothyroidism. J Clin Endocrinol Metab 2021; 106:e4400.
  20. Rubino DM, Greenway FL, Khalid U, et al. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial. JAMA 2022; 327:138.
  21. Kanie T, Mizuno A, Takaoka Y, et al. Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors for people with cardiovascular disease: a network meta-analysis. Cochrane Database Syst Rev 2021; 10:CD013650.
  22. Zhang Y, Sun Y, He Z, et al. Age-specific thyrotropin references decrease over-diagnosis of hypothyroidism in elderly patients in iodine-excessive areas. Clin Endocrinol (Oxf) 2021.
  23. Sweitzer B, Rajan N, Schell D, et al. Preoperative Care for Cataract Surgery: The Society for Ambulatory Anesthesia Position Statement. Anesth Analg 2021; 133:1431.
  24. Wang C, Johansson ALV, Rodriguez-Wallberg KA, et al. Long-term Follow-up of Psychiatric Disorders in Children and Adolescents Conceived by Assisted Reproductive Techniques in Sweden. JAMA Psychiatry 2022; 79:133.
  25. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/Adult_OI.pdf (Accessed on August 19, 2021).
  26. Gardellini A, Guidotti F, Maino E, et al. Severe immune thrombocytopenia after COVID-19 vaccination: Report of four cases and review of the literature. Blood Cells Mol Dis 2021; 92:102615.
  27. Visser C, Swinkels M, van Werkhoven E, et al. COVID-19 vaccination in patients with immune thrombocytopenia. Blood Adv 2021.
  28. Bravo-Pérez C, Serna MJ, Esteban J, et al. Anticoagulant therapy in patients with congenital FXI deficiency. Blood Adv 2021; 5:4083.
  29. Ingason AB, Hreinsson JP, Ágústsson AS, et al. Rivaroxaban Is Associated With Higher Rates of Gastrointestinal Bleeding Than Other Direct Oral Anticoagulants : A Nationwide Propensity Score-Weighted Study. Ann Intern Med 2021; 174:1493.
  30. Connors JM, Brooks MM, Sciurba FC, et al. Effect of Antithrombotic Therapy on Clinical Outcomes in Outpatients With Clinically Stable Symptomatic COVID-19: The ACTIV-4B Randomized Clinical Trial. JAMA 2021; 326:1703.
  31. Gupta A, Gonzalez-Rojas Y, Juarez E, et al. Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab. N Engl J Med 2021; 385:1941.
  32. Gottlieb RL, Vaca CE, Paredes R, et al. Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients. N Engl J Med 2022; 386:305.
  33. Hammond J, Leister-Tebbe H, Gardner A, et al. Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19. N Engl J Med 2022.
  34. Sullivan DJ, Gebo KA, Shoham S, et al. Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma. medRxiv 2021.
  35. Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients. N Engl J Med 2022; 386:509.
  36. US Food and Drug Administration. Fact sheet for healthcare providers: Emergency Use Authorization for bebtelovimab. Available at: https://www.fda.gov/media/156152/download (Accessed on February 16, 2022).
  37. The COVID-19 Treatment Guidelines Panel’s Interim Statement on Patient Prioritization for Outpatient Anti-SARS-CoV-2 Therapies or Preventive Strategies When There Are Logistical or Supply Constraints https://www.covid19treatmentguidelines.nih.gov/therapies/statement-on-patient-prioritization-for-outpatient-therapies/ (Accessed on December 23, 2021).
  38. United States Centers for Disease Control and Prevention. What We Know About Quarantine and Isolation. https://www.cdc.gov/coronavirus/2019-ncov/if-you-are-sick/quarantine-isolation-background.html (Accessed on January 05, 2022).
  39. Balocco R, De Sousa Guimaraes Koch S, Thorpe R, et al. New INN nomenclature for monoclonal antibodies. Lancet 2022; 399:24.
  40. World Health Organization. A clinical case definition of post-COVID-19 condition by a Delphi consensus, 6 October 2021. https://www.who.int/publications/i/item/WHO-2019-nCoV-Post_COVID-19_condition-Clinical_case_definition-2021.1 (Accessed on October 11, 2021).
  41. Workowski KA, Bachmann LH, Chan PA, et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep 2021; 70:1.
  42. Neal B, Wu Y, Feng X, et al. Effect of Salt Substitution on Cardiovascular Events and Death. N Engl J Med 2021; 385:1067.
  43. Silber MH, Buchfuhrer MJ, Earley CJ, et al. The Management of Restless Legs Syndrome: An Updated Algorithm. Mayo Clin Proc 2021; 96:1921.
  44. Ailani J, Lipton RB, Goadsby PJ, et al. Atogepant for the Preventive Treatment of Migraine. N Engl J Med 2021; 385:695.
  45. Akbar U, McQueen RB, Bemski J, et al. Prognostic predictors relevant to end-of-life palliative care in Parkinson's disease and related disorders: a systematic review. J Neurol Neurosurg Psychiatry 2021.
  46. Halliday A, Bulbulia R, Bonati LH, et al. Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy. Lancet 2021; 398:1065.
  47. Tariot PN, Cummings JL, Soto-Martin ME, et al. Trial of Pimavanserin in Dementia-Related Psychosis. N Engl J Med 2021; 385:309.
  48. Hwang YJ, Alexander GC, An H, et al. Risk of Hospitalization and Death Associated With Pimavanserin Use in Older Adults With Parkinson Disease. Neurology 2021; 97:e1266.
  49. Moulson N, Petek BJ, Drezner JA, et al. SARS-CoV-2 Cardiac Involvement in Young Competitive Athletes. Circulation 2021; 144:256.
  50. Khan F, Tritschler T, Kimpton M, et al. Long-Term Risk for Major Bleeding During Extended Oral Anticoagulant Therapy for First Unprovoked Venous Thromboembolism : A Systematic Review and Meta-analysis. Ann Intern Med 2021; 174:1420.
  51. Lewis G, Marston L, Duffy L, et al. Maintenance or Discontinuation of Antidepressants in Primary Care. N Engl J Med 2021; 385:1257.
  52. Okike K, King RK, Merchant JC, et al. Rapidly Destructive Hip Disease Following Intra-Articular Corticosteroid Injection of the Hip. J Bone Joint Surg Am 2021; 103:2070.
  53. Paget LDA, Reurink G, de Vos RJ, et al. Effect of Platelet-Rich Plasma Injections vs Placebo on Ankle Symptoms and Function in Patients With Ankle Osteoarthritis: A Randomized Clinical Trial. JAMA 2021; 326:1595.
  54. American College of Rheumatology COVID-19 Vaccine Clinical Guidance Summary for Patients with Rheumatic and Musculoskeletal Diseases (August 19,2021 update). https://www.rheumatology.org/Portals/0/Files/COVID-19-Vaccine-Clinical-Guidance-Rheumatic-Diseases-Summary.pdf (Accessed on August 21, 2021).
  55. Suzuki J, Mittal L, Woo SB. Sublingual buprenorphine and dental problems: a case series. Prim Care Companion CNS Disord 2013; 15.
  56. https://www.fda.gov/media/155352/download.
  57. Nguyen VH, Harley KG. Prenatal Cannabis Use and Infant Birth Outcomes in the Pregnancy Risk Assessment Monitoring System. J Pediatr 2022; 240:87.
  58. 100,000 Genomes Project Pilot Investigators, Smedley D, Smith KR, et al. 100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care - Preliminary Report. N Engl J Med 2021; 385:1868.
  59. Young-Wolff KC, Ray GT, Alexeeff SE, et al. Rates of Prenatal Cannabis Use Among Pregnant Women Before and During the COVID-19 Pandemic. JAMA 2021; 326:1745.
Topic 8357 Version 10977.0

References

1 : Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged≥19 Years: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022.

2 : Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged≥19 Years: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022.

3 : Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged≥19 Years: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022.

4 : Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged≥19 Years: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022.

5 : Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged≥19 Years: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022.

6 : Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged≥19 Years: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022.

7 : Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged≥19 Years: Recommendations of the Advisory Committee on Immunization Practices - United States, 2022.

8 : In Vitro Fertilization and Early Pregnancy Outcomes After Coronavirus Disease 2019 (COVID-19) Vaccination.

9 : Influenza Vaccine Uptake and Missed Opportunities Among the Medicare-Covered Population With High-Risk Conditions During the 2018 to 2019 Influenza Season : A Retrospective Cohort Study.

10 : The Risk of Allergic Reaction to SARS-CoV-2 Vaccines and Recommended Evaluation and Management: A Systematic Review, Meta-Analysis, GRADE Assessment, and International Consensus Approach.

11 : Symptoms After COVID-19 Vaccination in Patients With Persistent Symptoms After Acute Infection: A Case Series.

12 : Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021-22 Influenza Season.

13 : Efficacy of a Cell-Culture-Derived Quadrivalent Influenza Vaccine in Children.

14 : Efficacy of a Cell-Culture-Derived Quadrivalent Influenza Vaccine in Children.

15 : Risk for Recurrent Venous Thromboembolism and Bleeding With Apixaban Compared With Rivaroxaban: An Analysis of Real-World Data.

16 : Interventions to Improve Communication at Hospital Discharge and Rates of Readmission: A Systematic Review and Meta-analysis.

17 : Efficacy of Acupuncture for Chronic Prostatitis/Chronic Pelvic Pain Syndrome : A Randomized Trial.

18 : Urticaria: The 1-1-1 Criterion for Optimized Risk Stratification inβ-Lactam Allergy Delabeling.

19 : Comparative Effectiveness of Levothyroxine, Desiccated Thyroid Extract, and Levothyroxine+Liothyronine in Hypothyroidism.

20 : Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial.

21 : Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors for people with cardiovascular disease: a network meta-analysis.

22 : Age-specific thyrotropin references decrease over-diagnosis of hypothyroidism in elderly patients in iodine-excessive areas.

23 : Preoperative Care for Cataract Surgery: The Society for Ambulatory Anesthesia Position Statement.

24 : Long-term Follow-up of Psychiatric Disorders in Children and Adolescents Conceived by Assisted Reproductive Techniques in Sweden.

25 : Long-term Follow-up of Psychiatric Disorders in Children and Adolescents Conceived by Assisted Reproductive Techniques in Sweden.

26 : Severe immune thrombocytopenia after COVID-19 vaccination: Report of four cases and review of the literature.

27 : COVID-19 vaccination in patients with immune thrombocytopenia.

28 : Anticoagulant therapy in patients with congenital FXI deficiency.

29 : Rivaroxaban Is Associated With Higher Rates of Gastrointestinal Bleeding Than Other Direct Oral Anticoagulants : A Nationwide Propensity Score-Weighted Study.

30 : Effect of Antithrombotic Therapy on Clinical Outcomes in Outpatients With Clinically Stable Symptomatic COVID-19: The ACTIV-4B Randomized Clinical Trial.

31 : Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab.

32 : Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients.

33 : Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19.

34 : Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma.

35 : Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients.

36 : Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients.

37 : Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients.

38 : Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients.

39 : New INN nomenclature for monoclonal antibodies.

40 : New INN nomenclature for monoclonal antibodies.

41 : Sexually Transmitted Infections Treatment Guidelines, 2021.

42 : Effect of Salt Substitution on Cardiovascular Events and Death.

43 : The Management of Restless Legs Syndrome: An Updated Algorithm.

44 : Atogepant for the Preventive Treatment of Migraine.

45 : Prognostic predictors relevant to end-of-life palliative care in Parkinson's disease and related disorders: a systematic review.

46 : Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy.

47 : Trial of Pimavanserin in Dementia-Related Psychosis.

48 : Risk of Hospitalization and Death Associated With Pimavanserin Use in Older Adults With Parkinson Disease.

49 : SARS-CoV-2 Cardiac Involvement in Young Competitive Athletes.

50 : Long-Term Risk for Major Bleeding During Extended Oral Anticoagulant Therapy for First Unprovoked Venous Thromboembolism : A Systematic Review and Meta-analysis.

51 : Maintenance or Discontinuation of Antidepressants in Primary Care.

52 : Rapidly Destructive Hip Disease Following Intra-Articular Corticosteroid Injection of the Hip.

53 : Effect of Platelet-Rich Plasma Injections vs Placebo on Ankle Symptoms and Function in Patients With Ankle Osteoarthritis: A Randomized Clinical Trial.

54 : Effect of Platelet-Rich Plasma Injections vs Placebo on Ankle Symptoms and Function in Patients With Ankle Osteoarthritis: A Randomized Clinical Trial.

55 : Sublingual buprenorphine and dental problems: a case series.

56 : Sublingual buprenorphine and dental problems: a case series.

57 : Prenatal Cannabis Use and Infant Birth Outcomes in the Pregnancy Risk Assessment Monitoring System.

58 : 100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care - Preliminary Report.

59 : Rates of Prenatal Cannabis Use Among Pregnant Women Before and During the COVID-19 Pandemic.