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What's new in family medicine

What's new in family medicine
Authors:
Lisa Kunins, MD
Jane Givens, MD, MSCE
Literature review current through: Feb 2022. | This topic last updated: Mar 01, 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.

ADULT GENERAL INTERNAL MEDICINE

Prolonged duration of symptoms in COVID-19 ICU survivors (February 2022)

The duration of symptoms following COVID-19 is unclear. A recent study reported that three-quarters of intensive care unit COVID-19 survivors had physical symptoms at one year. These included physical weakness (39 percent), joint symptoms (26 percent), and myalgia (21 percent) [1]. Mental symptoms were reported by 26 percent and cognitive symptoms by 16 percent of survivors. These symptoms are consistent with post-intensive care syndrome (PICS) and need to be addressed during recovery from COVID-19. (See "COVID-19: Evaluation and management of adults following acute viral illness", section on 'Persistent symptoms'.)

Cannabis edible product ingestion in US children (October 2021)

Concentrated edible cannabis (marijuana) products are popular for recreational use. Exploratory ingestions of these products in young children can cause severe toxicity including seizures, apnea, and coma. In a report from the United States National Poison Data System, cannabis edible product ingestions have significantly increased in children <5 years old, with over twice the rate of exposures from states where adult cannabis use is legal [2]. These findings indicate an urgent need for education of adult cannabis users regarding the dangers that edible cannabis products pose to young children and for legislative efforts to prohibit cannabis product packaging and advertising that target children. (See "Cannabis (marijuana): Acute intoxication", section on 'Recreational use'.)

Randomized trial of goal blood pressure in older adults (October 2021)

UpToDate recommends intensive blood pressure lowering in hypertensive older adults, based in part upon findings from the Systolic Pressure Intervention Trial (SPRINT). In the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial, more than 8000 Chinese adults aged 60 to 80 years were randomly assigned to either a more intensive (goal systolic pressure <130 mmHg) or a less intensive (goal systolic pressure <150 mmHg) blood pressure lowering strategy [3]. Those assigned to more intensive blood pressure lowering had modestly lower rates of stroke, acute coronary syndrome, and heart failure at approximately three years; major adverse events were similar between the groups. The STEP trial findings are broadly consistent with those from SPRINT and support our recommendation for intensive blood pressure lowering in hypertensive older adults. (See "Goal blood pressure in adults with hypertension", section on 'Older adults'.)

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 [4]. 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 [5]. 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'.)

GERIATRICS

Randomized trial of goal blood pressure in older adults (October 2021)

UpToDate recommends intensive blood pressure lowering in hypertensive older adults, based in part upon findings from the Systolic Pressure Intervention Trial (SPRINT). In the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial, more than 8000 Chinese adults aged 60 to 80 years were randomly assigned to either a more intensive (goal systolic pressure <130 mmHg) or a less intensive (goal systolic pressure <150 mmHg) blood pressure lowering strategy [3]. Those assigned to more intensive blood pressure lowering had modestly lower rates of stroke, acute coronary syndrome, and heart failure at approximately three years; major adverse events were similar between the groups. The STEP trial findings are broadly consistent with those from SPRINT and support our recommendation for intensive blood pressure lowering in hypertensive older adults. (See "Goal blood pressure in adults with hypertension", section on 'Older adults'.)

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 [6]; 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 [7-10]. 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) [11,12]. 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'.)

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 [13]. 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 [14]. 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 [15]. 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 [16]. 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 [17,18]. 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'.)

PREVENTION

New threshold for elevated blood lead in United States children (November 2021)

Detectable blood lead levels (BLLs) are associated with neurocognitive deficits in infants and children <6 years old, and targeted screening of at-risk children is recommended. The Centers for Disease Control and Prevention has lowered the blood lead level (BLL) threshold for action to 3.5 mcg/dL (0.17 micromol/L) from the previous level of 5.0 mcg/dL (0.24 micromol/L) [19,20]. At or above this threshold, specific interventions should be taken based upon the degree of BLL elevation (table 4). For children with BLLs below 3.5 mcg/dL, the limit of detection for lead varies by laboratory, and the actual blood lead value may be close to or above the threshold. Thus, some children may need to be retested depending upon age or other risk factors. (See "Childhood lead poisoning: Management", section on 'Approach'.)

ADULT DERMATOLOGY

Topical spinosad for scabies (September 2021)

Spinosad is an insecticide derived from fermentation of a soil actinobacterium and causes fatal neuronal excitation in insects, including the parasites responsible for scabies. In the combined results from two phase 3 randomized trials (551 adults and children with scabies), 78 percent of patients treated with a single application of spinosad 0.9% topical suspension achieved complete cure compared with only 40 percent of patients in the vehicle group [21]. Treatment was well tolerated. These findings support spinosad as a topical therapy for scabies and contributed to the US Food and Drug Administration (FDA) approval of spinosad for this indication. The efficacy of spinosad has not been directly compared with the currently preferred therapies (topical permethrin or oral ivermectin). (See "Scabies: Management".)

ADULT 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 [22]. 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 [23]. 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 [24]. 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 [25]. 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'.)

ADULT HEMATOLOGY AND ONCOLOGY

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) [26]. 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".)

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 [27]. 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 [28]. 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'.)

ADULT 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 [29-32]. For outpatient adults who have mild-to-moderate COVID-19 and are at risk for progression to severe disease (table 5), 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 [33]. Bebtelovimab is an alternative monoclonal antibody that is active against Omicron, but there are limited data to support its use [34]. 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 6) [35]. (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 [36]. 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'.)

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") [37]. 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 [38]. 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'.)

ADULT 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 [39]. 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'.)

ADULT NEUROLOGY AND 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 [40]. 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'.)

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 [41]. 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) [42]. 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 [43]. 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 [44]. 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 [45].

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 [46]. 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'.)

ADULT PULMONOLOGY

Updated guidelines on venous thromboembolism management (January 2022)

Updated guidelines on the treatment of venous thromboembolism (VTE) were published by the American College of Chest Physicians (CHEST) [47]. Many recommendations are similar to those in the 2016 guideline but either expanded in scope or changed in strength of the recommendation. As new recommendations, for most patients with cancer-related VTE, CHEST suggests a direct oral anticoagulant (DOAC) rather than low molecular weight heparin. For select patients without cancer who require extended anticoagulation beyond the conventional period of three to six months, CHEST suggests low-intensity anticoagulation with a DOAC. While CHEST did not promote aspirin for VTE prevention, they suggest that it may reduce the risk of recurrence when compared with no therapy. (See "Overview of the treatment of lower extremity deep vein thrombosis (DVT)" and "Anticoagulation therapy for venous thromboembolism (lower extremity venous thrombosis and pulmonary embolism) in adult patients with malignancy" and "Selecting adult patients with lower extremity deep venous thrombosis and pulmonary embolism for indefinite anticoagulation".)

Comparison of protocols for the diagnosis of pulmonary embolism (January 2022)

The ideal strategy for diagnosing pulmonary embolism (PE) is unknown. One meta-analysis reported that protocols that used pretest probability (PTP) models, adjusted D-Dimer levels, and/or YEARs criteria excluded more cases of PE without imaging (high efficiency) [48]. However, they also had the highest failure rate (ie, more missed cases of VTE). In addition, such protocols did not perform uniformly across all subgroups, with the lowest efficiency observed in those who were 80 years of age or older and in patients with cancer. In patients with suspected PE, we prefer to use a conventional protocol that combines clinical PTP and unadjusted D-Dimer to direct imaging. Although this approach is associated with a higher rate of imaging, fewer cases of PE are missed and we value the role of imaging when looking for alternate causes of patients' symptoms. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Adjusted D-dimer'.)

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) [49]. 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'.)

ADULT 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) [50]. 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 [51]. 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 [52]. 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'.)

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 [53]. 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'.)

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 [54]. 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'.)

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 [55]. 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'.)

OBSTETRICS

COVID-19 vaccination in pregnancy improves infant outcomes (February 2022)

COVID-19 vaccination of pregnant women reduces serious maternal and pregnancy morbidity from infection. In an analysis of data from 20 pediatric hospitals in the United States during a period of Delta and Omicron variant circulation, infants <6 months of age were 61 percent less likely to be hospitalized with COVID-19 if their mothers became fully vaccinated with an mRNA COVID-19 vaccine during pregnancy [56]. Furthermore, 88 percent of the intensive care unit admissions for COVID-19 and the only death occurred among infants of unvaccinated mothers. Thus, maternal vaccination also appears to protect infants in the first six months of life. (See "COVID-19: Overview of pregnancy issues", section on 'Safety and efficacy'.)

TORCH screening not useful in isolated fetal growth restriction (February 2022)

Maternal TORCH (toxoplasmosis, other, rubella, cytomegalovirus [CMV], herpes) serology does not appear to be useful in the work-up of isolated fetal growth restriction (FGR). In a systematic review including nearly 500 maternal TORCH screens in pregnancies with FGR <10th percentile, 10 congenital infections were ultimately detected (8 CMV, 2 parvovirus B19), but only 2 of the 10 fetuses had isolated FGR (both had CMV) [57]. Given this low yield, we agree with the Society for Maternal-Fetal Medicine recommendation against routine TORCH serology for isolated FGR. We limit serology studies to cases with both FGR plus ultrasound findings suggestive of fetal infection and cases in which maternal history and physical examination suggest an acute infection. (See "Fetal growth restriction: Evaluation and management", section on 'Work-up for infection'.)

COVID-19 vaccination improves outcomes of infected pregnant patients (February 2022, Modified February 2022)

A recent population-based study of over 18,000 pregnant patients in Scotland provides the first evidence of more favorable pregnancy outcomes among those who have received COVID-19 vaccination [58]. In pregnant patients with COVID-19, unvaccinated individuals represented a significantly higher proportion of COVID-19-associated hospital admissions (77 percent), COVID-19-associated critical care admissions (98 percent), and perinatal deaths (100 percent of stillbirths and neonatal deaths). The perinatal death rate in the vaccinated cohort was similar to historical background rates and the rates in pregnant people without COVID-19. These findings further support universal recommendations for pregnant people to be up-to-date with COVID-19 vaccination. (See "COVID-19: Overview of pregnancy issues", section on 'Safety and efficacy'.)

Maternal hydroxyprogesterone caproate exposure and cancer risk in offspring (January 2022)

Few studies have evaluated long-term outcomes of fetuses exposed to maternal progesterone supplementation for prevention of preterm birth. A retrospective population-based study including >18,000 mother-child dyads now reports that offspring of mothers who received hydroxyprogesterone caproate (17-OHPC) during pregnancy between 1959 and 1966 were at increased risk of any cancer (incidence: 30 versus 14 per 100,000 persons; adjusted hazard ratio 2.6) [59]. Most exposures were in the first trimester in patients with threatened abortion. Whether this association is germane to the current use of 17-OHPC beginning at 16 to 20 weeks to prevent preterm birth is not known. (See "Progesterone supplementation to reduce the risk of spontaneous preterm labor and birth", section on 'Safety, side effects, and adverse effects'.)

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 [60]. 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'.)

Placental abruption and future risk of cardiovascular disease (January 2022)

Accumulating data support the hypothesis that abnormalities of placental development are a harbinger of future maternal cardiovascular disease (CVD). In a meta-analysis of 11 cohort studies including over 6 million pregnancies, nearly 70,000 abruptions, and nearly 50,000 cases of CVD (including stroke), the risk of future morbidity/mortality from CVD was significantly higher among patients with abruption (17 versus 9 per 1000 births) and positively correlated with the number of abruptions [61]. Based on these and other findings, patients who have had an abruption may benefit from postpartum counseling and interventions to mitigate future CVD risk. (See "Placental abruption: Management and long-term prognosis", section on 'Long-term maternal prognosis'.)

Prophylactic negative pressure wound therapy after cesarean birth (December 2021)

The value of prophylactic negative pressure wound therapy (pNPWT) after cesarean birth is under investigation. In a meta-analysis of trials comparing pNPWT with standard wound care in patients with obesity undergoing cesarean birth, the intervention reduced the risk of surgical site infection (SSI) (1.7 versus 8.3 percent; RR 0.79, 95% CI 0.65-0.95) but not other wound complications (eg, dehiscence, seroma), readmission, or reoperation, and it increased skin blistering [62]. Limitations of the analysis included practice variations in surgical care, inconsistent definitions, lack of blinding, and industry sponsorship of some trials. Additional rigorous research is needed before pNPWT can be recommended for patients with obesity undergoing cesarean birth. (See "Cesarean birth: Patients with obesity", section on 'Negative pressure wound therapy'.)

Behavioral interventions and SGA (December 2021)

Small for gestational age (SGA) infants are at increased risk for morbidity and mortality and tend to recur in subsequent pregnancies. In a trial of over 1200 pregnancies at high risk for birth of an SGA infant, participants were randomly assigned to a structured Mediterranean diet, mindfulness-based stress reduction, or usual care from 20 weeks of gestation to delivery. The rate of SGA births was significantly lower for both structured diet (14 percent) and stress reduction (16 percent) compared with usual care (22 percent) [63]. These findings should be interpreted with caution since the trial had several limitations, including a higher proportion of SGA risk factors in the usual care group. However, both interventions are considered healthy behavioral changes that are reasonable in any pregnancy. (See "Fetal growth restriction: Evaluation and management", section on 'Prevention in subsequent pregnancies'.)

Prevalence of iron deficiency during pregnancy (December 2021)

A new retrospective study involving over 44,000 pregnant individuals suggests that a large proportion have iron deficiency, many in the absence of anemia [64]. Ferritin was low in over half (<15 ng/mL in 24 percent, <30 ng/mL in 53 percent) and borderline (30 to 44 ng/mL) in another 25 percent. Individuals with lower household income were less likely to be screened. These data support having a high level of suspicion for iron deficiency during pregnancy, being aware of possible health care disparities, testing individuals at high risk, and evaluating the cause in all patients with anemia. Iron deficiency is correlated with adverse maternal and fetal outcomes. (See "Anemia in pregnancy", section on 'Whether to screen for iron deficiency'.)

COVID-19 is associated with increased maternal death and stillbirth rates (November 2021)

Data continue to accumulate regarding the risks of SARS-CoV-2 infection in pregnancy:

In a report of COVID-19-related deaths in Mississippi, pregnant patients had a higher case fatality rate than nonpregnant females of reproductive age (9 versus 2.5 deaths per 1000 SARS-CoV-2 infections) [65]. Fourteen of the 15 maternal deaths were in patients with comorbidities and none of the 15 patients were fully vaccinated. (See "COVID-19: Overview of pregnancy issues".)

In an analysis of over 8000 stillbirths among 1.2 million delivery hospitalizations in the United States during the pandemic, pregnant COVID-19 patients had a higher stillbirth rate than those without COVID-19 (1.26 versus 0.64 percent of deliveries) [66]. (See "COVID-19: Overview of pregnancy issues", section on 'Pregnancy and newborn outcomes'.)

Although incomplete information and ascertainment bias limit interpretation, these findings provide further support for vaccinating pregnant patients and those planning pregnancy to reduce maternal and fetal death.

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) [67]. 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'.)

Gestational age at time of COVID-19 and outcome (September 2021)

In an international retrospective cohort study evaluating obstetric and neonatal outcomes of nearly 400 SARS-CoV-2-positive patients according to their gestational age at the time of infection, infection after 20 weeks increased the risk for adverse obstetric outcomes, and infection after 26 weeks increased the risk for adverse neonatal outcomes [68]. Given these findings, the increased severity of COVID-19 in pregnant women, the good safety profile of SARS-CoV-2 vaccines in pregnancy, and the time it takes to become fully vaccinated, we recommend vaccination as soon as possible for women planning to conceive and pregnant women. (See "COVID-19: Overview of pregnancy issues", section on 'Pregnancy and newborn outcomes'.)

Statins not effective for preventing preeclampsia (September 2021)

Statins are generally discontinued in pregnancy; however, data from animal studies and a small pilot trial in humans suggested statins may reduce the risk for preeclampsia. A multicenter randomized trial including over 1100 singleton pregnancies at high risk for term preeclampsia now reports that pravastatin 20 mg daily beginning at 35+0/7ths to 36+6/7ths weeks and continuing until birth did not reduce the incidence of preeclampsia or other adverse pregnancy outcomes compared with placebo [69]. A limitation of the trial is the late initiation and short duration of therapy. Appropriately powered randomized trials are needed to determine whether earlier initiation of therapy, use of higher doses, or use of more potent statins might be effective. (See "Preeclampsia: Prevention", section on 'Statins'.)

COVID-19 vaccination does not increase risk for miscarriage (September 2021)

Evidence of the safety of COVID-19 vaccination in pregnancy continues to accrue. In one study involving nearly 2500 pregnancies, the age-standardized cumulative risk of miscarriage was 12.8 percent individuals who received a mRNA COVID-19 vaccine preconception or prior to 20 weeks of gestation, which is similar to the expected miscarriage rate in the general obstetric population [70]. In another study including over 105,000 pregnancies, individuals who experienced miscarriage had similar odds of exposure to a COVID-19 vaccine in the prior 28 days as those with ongoing pregnancies [71]. Results were consistent with either mRNA-1273 or BNT162b2 vaccine exposure; risks specific to Ad26.COV.2.S vaccine could not be assessed due to a small number of exposures. We recommend COVID-19 vaccination regardless of pregnancy status. (See "COVID-19: Overview of pregnancy issues", section on 'Vaccination in people planning pregnancy and pregnant or recently pregnant people'.)

Timing of delivery in fetal growth restriction (August 2021)

There is little consensus about the optimum time to deliver the fetus with growth restriction (FGR). In a retrospective cohort study, infants who were severely small for gestational age (SGA, birth weight <3rd percentile) and delivered early for suspected FGR had poorer school outcomes in grades 3, 5, and 7 compared with infants with the same degree of SGA who were not suspected of having FGR (mean gestational age at birth: 37.9 versus 39.4 weeks) [72]. Although these findings suggest that avoiding early delivery of suspected FGR when safe to do so may improve school performance of SGA infants, other differences between the two groups may account for the better outcome. (See "Fetal growth restriction: Evaluation and management", section on 'Timing of delivery'.)

Maternal CMV immune globulin not effective for preventing congenital infection (August 2021)

Maternal hyperimmune globulin treatment of primary cytomegalovirus (CMV) infection in early pregnancy is an investigational approach for preventing symptomatic infection in offspring. In the largest trial of this therapy to date, which randomly assigned nearly 400 pregnant women with primary CMV infection before 24 weeks to a monthly infusion of CMV immune globulin or placebo until delivery, the composite outcome (congenital CMV infection or fetal/neonatal death if no CMV testing) was similar in both groups (23 versus 19 percent) [73]. There were no clear differences in individual outcomes (eg, death, preterm birth, birth weight <5th percentile). Given these and previous findings, practitioners should emphasize preventive behavioral measures against maternal CMV acquisition and limit use of hyperimmune globulin therapy to research studies. (See "Cytomegalovirus infection in pregnancy", section on 'CMV immune globulin'.)

PEDIATRICS: GENERAL PEDIATRICS

Omicron variant associated with increased COVID-19 hospitalizations in children (March 2022)

With predominance of the Omicron (B.1.1.529) SARS-CoV-2 variant in the United States, weekly COVID-19 hospitalization rates among children reached an all-time high in January 2022 (7.1 per 100,000 population) [74]. Hospitalization rates were particularly high (15.6 per 100,000 population) in children age 0 to 4 years, who are not eligible for vaccination. Despite increased rates of hospitalization, the proportion of children and adolescents requiring intensive care or invasive mechanical ventilation was lower with Omicron than earlier circulating strains. Greater proportions of unvaccinated than fully vaccinated adolescents had COVID-19 as the primary reason for hospitalization (70 versus 41 percent) and required intensive care (30 versus 16 percent), highlighting the benefits of vaccination. (See "COVID-19: Clinical manifestations and diagnosis in children", section on 'How often are children with COVID-19 hospitalized?'.)

COVID-19 vaccination improves outcomes of infected pregnant patients (February 2022, Modified February 2022)

A recent population-based study of over 18,000 pregnant patients in Scotland provides the first evidence of more favorable pregnancy outcomes among those who have received COVID-19 vaccination [58]. In pregnant patients with COVID-19, unvaccinated individuals represented a significantly higher proportion of COVID-19-associated hospital admissions (77 percent), COVID-19-associated critical care admissions (98 percent), and perinatal deaths (100 percent of stillbirths and neonatal deaths). The perinatal death rate in the vaccinated cohort was similar to historical background rates and the rates in pregnant people without COVID-19. These findings further support universal recommendations for pregnant people to be up-to-date with COVID-19 vaccination. (See "COVID-19: Overview of pregnancy issues", section on 'Safety and efficacy'.)

Duration of anticoagulation for low-risk provoked venous thromboembolism in pediatric patients (February 2022)

The optimal duration of anticoagulant therapy for children with venous thromboembolism (VTE) is uncertain. Usual practice has been to treat for three months based largely upon evidence from adult studies. However, a recent clinical trial suggests that six weeks of therapy is sufficient for most pediatric patients with low-risk provoked VTE (ie, attributable to a transient risk factor) [75]. The trial enrolled 417 children with provoked VTE (catheter-associated in 50 percent; infection-related in 30 percent; surgery- or trauma-related in 20 percent) who were randomly assigned to six weeks or three months of anticoagulant therapy. At one year, rates of VTE recurrence were similarly low in both groups (1.1 and 1.6 percent, respectively). Based upon these findings, we now suggest a six-week course of treatment for pediatric patients with provoked VTE who met all of the following low-risk criteria:

No prior history of VTE

The VTE is not severe or life-threatening

The provoking risk factor resolves within six weeks

The thrombus resolves or is nonocclusive within six weeks

For patients with provoked VTE who do not meet these criteria, we continue to suggest three months of therapy. (See "Venous thrombosis and thromboembolism (VTE) in children: Treatment, prevention, and outcome", section on 'Provoked VTE'.)

Vaccination against human papillomavirus, especially at an early age, is associated with greater reductions in cervical cancer (December 2021)

Human papillomavirus (HPV) vaccination has been shown to decrease incidence of HPV infection and cervical intraepithelial neoplasia (CIN), but whether vaccinating females at an earlier age is associated with lower incidence of cervical cancer has not been well established. In a registry-based observational study of 13.7 million years of follow-up of females aged 20 to 30 years, females who received the bivalent HPV vaccine at a younger age had a greater relative reduction in the incidence of cervical cancer and CIN3 (34 percent for vaccination at age 16 to 18 years, 62 percent at age 14 to 16 years, and 87 percent at age 12 to 13 years) compared with the unvaccinated cohort [76]. This lends further support to vaccinating against HPV at a younger age. (See "Human papillomavirus vaccination", section on 'Cervical, vaginal, and vulvar disease'.)

COVID-19 vaccination in children 5 years and older (November 2021)

In October 2021, the US Food and Drug Administration authorized BNT162b2 (Pfizer vaccine) for individuals 5 to 11 years old based on data from randomized trials in over 2000 children in this age group, which demonstrated 91 percent vaccine efficacy against symptomatic COVID-19 and immunogenicity similar to that in adolescents and young adults [77]. There were no cases of vaccine-associated myocarditis in the trials; although the precise risk is uncertain, it is expected to be lower than that seen in older individuals. We agree with recommendations from the Centers for Disease Control and Prevention to give BNT162b2 to children ages 5 to 11 years. Clinicians should be aware that the dose and formulation used for children are different than those for adolescents and adults. (See "COVID-19: Vaccines", section on 'Summary and recommendations'.)

Pediatric fatalities associated with over-the-counter cough and cold medications (November 2021)

Manufacturer labelling and US Food and Drug Administration recommendations strongly advise against the use of over-the-counter cough and cold medications (CCM) in young children. A new report describes fatalities identified by a United States surveillance system and associated with CCM ingestion in children <12 years of age from 2008 to 2016 [78]. During this period, there were 40 reported deaths; the majority occurred in children <2 years old and involved diphenhydramine. Root cause analysis determined that 13 deaths occurred after deliberate supratherapeutic administration by a caregiver with the goal of sedating or harming the child. Health care providers should continue to educate caregivers on the dangers of CCM in children and maintain a high index of suspicion for child abuse with a low threshold for toxicology testing in infants and young children with unexplained signs or symptoms compatible with drug toxicity. (See "Physical child abuse: Diagnostic evaluation and management", section on 'Toxicology'.)

Point-of-care lead testing kit recall (October 2021)

Certain lots of point-of-care capillary blood lead testing kits manufactured by Magellan Diagnostics, Inc (LeadCare II, LeadCare Plus, and LeadCare Ultra) and distributed after October 27, 2020 have been recalled by the manufacturer and the US Food and Drug Administration (FDA) because of a significant risk of falsely low results. Per the FDA, children and pregnant or breastfeeding individuals who had test results <3.5 mcg/dL (0.14 micromol/L) using either a recalled test kit or a test kit with an unknown lot number should be retested with a venous blood lead level, especially those with potential signs or symptoms of lead toxicity or who are at high risk for lead exposure [79,80]. Remaining recalled test kits should be quarantined and no longer used. (See "Childhood lead poisoning: Clinical manifestations and diagnosis", section on 'Lead levels'.)

Iron deficiency anemia in children and neurocognitive deficits (October 2021)

Observational studies from low- and middle-income countries show an association between iron deficiency anemia (IDA) and neurodevelopmental deficits. A new randomized trial in more than 3000 infants in rural Bangladesh (one-third with iron deficiency and one-fifth with IDA at baseline) evaluated the effect of iron supplementation (alone or with other micronutrients, compared with placebo) for three months starting in late infancy [81]. Iron supplementation effectively reduced the prevalence of IDA, but there were no significant differences between the three groups on neurocognitive tests or growth outcomes at study completion or nine months later, including in the subgroup with IDA. Thus, the association between IDA and neurocognitive development may not be causal, or the timing and duration of the iron supplementation in this study was insufficient to detect such an effect. Despite these results, IDA has other adverse health effects, and routine screening of young children is warranted. (See "Iron deficiency in infants and children <12 years: Screening, prevention, clinical manifestations, and diagnosis", section on 'Associated disorders and effects of treatment'.)

Severe consequences of feeding a homemade vegan infant formula (October 2021)

Case reports describe life-threatening consequences of feeding a homemade plant-based formula to infants. The infants presented with acute respiratory distress, severe life-threatening hypocalcemia, hypophosphatemia, and rickets, with or without hypothyroidism, and some experienced seizure or cardiac arrest [82,83]. The formulas were made by the parents, following a vegan or "alkaline diet" recipe that they perceived to be healthy, but that lacked essential vitamins and minerals, including vitamin D, calcium, and iodine. These reports support our recommendation to provide explicit nutritional guidance to families who follow a vegan diet, and advise them not to feed homemade formulas to infants [84]. (See "Vegetarian diets for children", section on 'Plant-based formulas and beverages'.)

Childhood obesity during the COVID-19 pandemic (September 2021)

In a retrospective cohort study of more than 190,000 children who had at least one body mass index measurement before and during the first year of the pandemic, obesity rates rose from pre-pandemic levels among all age groups. The increase by age groups was from 19 to 26 percent for 5- to 11-year-olds, from 19 to 23 percent for 12- to 15-year-olds, and from 18 to 20 percent for 16- to 17-year-olds [85]. Other studies report that the pandemic exacerbated risk factors for obesity including reduced physical activity, increased screen time, and access to unhealthy foods; studies also observed an increase in preexisting disparities in obesity rates between racial/ethnic and income groups [86,87]. (See "Definition, epidemiology, and etiology of obesity in children and adolescents", section on 'Trends'.)

Direct oral anticoagulants for venous thromboembolism in children ≥2 years (August 2021)

In 2021, the US Food and Drug Administration approved two direct oral anticoagulants (DOACs), dabigatran and rivaroxaban, for treatment of venous thrombosis and thromboembolism (VTE) in children [88,89]. These regulatory approvals were based upon two large multicenter pediatric trials demonstrating that dabigatran and rivaroxaban have similar efficacy and bleeding risk compared with low molecular weight heparin (LMWH) and warfarin [90,91]. Adolescents made up most of the trial populations, and children <2 years were underrepresented. DOACs are an attractive option since they are orally administered and do not require drug monitoring. We now suggest one of the approved DOACs (dabigatran or rivaroxaban) for treatment of VTE in adolescents, after at least five days of initial parenteral therapy. For children ages 2 to 11 years, either a DOAC or LMWH is acceptable. For infants and children <2 years, the efficacy and safety of DOACs remain uncertain, and we continue to suggest LMWH. (See "Venous thrombosis and thromboembolism (VTE) in children: Treatment, prevention, and outcome", section on 'Direct oral anticoagulants'.)

AAP clinical practice guidelines for febrile infants 8 to 60 days old (August 2021)

The American Academy of Pediatrics (AAP) has published multidisciplinary, consensus guidelines for the evaluation and management of well-appearing, healthy febrile infants 8 to 60 days old at low risk for invasive bacterial infection (bacteremia or meningitis) (algorithm 4 and algorithm 5 and algorithm 6) [92]. Key changes from prior guidelines include the use of inflammatory markers to identify infants 29 to 60 days old in whom lumbar puncture (LP) need not be performed and neonates 22 to 28 days old who may not require LP and a recommendation against sending a urine culture in infants with normal a normal urinalysis. Febrile infants 29 to 60 days of age with normal inflammatory markers and urinalysis may be managed at home by reliable caregivers as long as close follow-up is assured. These guidelines are consistent with our approach, although sending a urine culture on all febrile young infants is reasonable in facilities where contamination rates are low. (See "The febrile infant (29 to 90 days of age): Outpatient evaluation", section on '29 to 60 days old' and "The febrile neonate (28 days of age or younger): Outpatient evaluation and initial management", section on '22 to 28 days old' and "The febrile infant (29 to 90 days of age): Management", section on 'Infants 29 to 60 days old'.)

Use of palivizumab during increased interseasonal activity of respiratory syncytial virus (RSV) (August 2021)

During the coronavirus disease 2019 (COVID-19) pandemic, increased interseasonal activity of RSV has resulted in more hospitalizations and emergency department visits for infants in some regions. The American Academy of Pediatrics suggests administration of palivizumab for RSV prophylaxis in eligible infants outside of the typically recommended schedule if they live in regions with interseasonal RSV activity similar to that in a typical fall-winter season [93]. In the United States, information about state-level RSV activity is available from the Centers for Disease Control and Prevention. Health departments in the United Kingdom began offering palivizumab to eligible infants in July and have extended the number of doses from five to seven [94]. Eligibility criteria for palivizumab treatment vary geographically. (See "Respiratory syncytial virus infection: Prevention in infants and children", section on 'Increased interseasonal activity during COVID-19 pandemic'.)

PEDIATRICS: DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS

Sleep problems in children with ADHD during the COVID-19 pandemic (September 2021)

Sleep disturbances are common in children with attention deficit hyperactivity disorder (ADHD), and home confinement associated with the COVID-19 pandemic has exacerbated prepandemic problems. In a survey study of nearly 1000 parents of children aged 5 to 18 years with ADHD, 60 to 70 percent of children had a change in bedtime during confinement, and the frequency of bedtimes later than 11 PM substantially increased [95]. Sleep duration changes were bidirectional, with more children sleeping less than 6 hours or between 10 and 11 hours per night. Management of sleep problems in children with ADHD begins with setting consistent sleep-wake schedules and treating behavioral contributors such as excess screen time near bedtime and anxiety (table 7A-B). (See "Sleep in children and adolescents with attention deficit hyperactivity disorder", section on 'Common sleep complaints'.)

SURGERY

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 [96]. (See "Anesthesia for elective eye surgery", section on 'Anesthetic considerations'.)

Consensus on guiding principles for perioperative pain management (October 2021)

Evidence-based multidisciplinary guidelines for the management of acute perioperative pain have been lacking. Recently, a consortium of various specialty organizations published consensus recommendations for seven guiding principles for perioperative pain management (table 8) [97]. We agree with these principles, which seek to improve perioperative pain management by implementing multimodal, opioid-sparing, patient-centered approaches. (See "Management of acute perioperative pain", section on 'General approach'.)

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Topic 8349 Version 10977.0

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