What's new in family medicine

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

Semaglutide in patients with heart failure with preserved ejection fraction and obesity (September 2023)

In patients with heart failure with preserved ejection fraction (HFpEF), weight loss is likely to improve functional status and quality of life, but achieving weight loss in this group of patients is difficult. In a recent trial of more than 500 patients with HFpEF, patients randomly assigned to treatment with semaglutide had greater improvement in exercise capacity (ie, six-minute walk distance), quality of life, and weight loss (-13 percent mean change in body weight versus -2.6 percent) at 52 weeks than patients assigned to placebo [1]. An exploratory analysis suggested a lower risk of urgent HF hospitalizations in those treated with semaglutide. Similar to other patients with obesity, patients with HFpEF and obesity should receive appropriate management to achieve weight loss. (See "Treatment and prognosis of heart failure with preserved ejection fraction", section on 'Obesity'.)

Over-the-counter opioid antagonist for opioid overdose (September 2023)

Drug overdose is a major public health problem; opioids were reported to be involved in nearly 80 percent of the 600,000 overdose deaths worldwide in 2019. The increasing rate of fatal overdose is driven by the presence of the synthetic opioid fentanyl. Naloxone 4 mg nasal spray rapidly reverses the effects of opioid overdose and is now the first opioid antagonist agent available for over-the-counter purchase in the United States [2]. The increased availability is part of an ongoing effort by the US Food and Drug Administration Overdose Prevention Framework to encourage harm reduction through developing and expanding access to novel overdose reversal products. (See "Prevention of lethal opioid overdose in the community", section on 'Community-based naloxone'.)

No benefit of opioids for acute low back pain (August 2023)

Opioid analgesics are often used to treat acute low back pain despite limited supporting evidence. In a randomized trial of 347 adults presenting to the emergency department or primary care clinic with acute, nonspecific low back pain, oxycodone (up to 20 mg daily for six weeks) was no more effective for pain relief or functional improvement than placebo [3]. There was a higher risk of potential opioid misuse in patients in the oxycodone group at one-year follow-up (20 versus 10 percent). These results support our recommendation against routine opioid use for acute low back pain, given the lack of benefit and potential for misuse. (See "Treatment of acute low back pain", section on 'Opioids'.)

Exercise and cardiovascular risk reduction (July 2023)

Current guidelines from the American Heart Association and World Health Organization recommend at least 150 minutes of moderate-to-vigorous physical activity weekly. Two recent studies suggest that how one exercises matters more than when. In one prospective cohort of over 500,000 individuals, combining twice-weekly muscle strengthening activity to at least 150 minutes of moderate-to-vigorous physical activity was associated with optimal reductions in all-cause and cardiovascular mortality [4]. In a separate study of nearly 90,000 individuals, among those who had at least 150 minutes of weekly physical activity, "weekend warrior" patterns of exercise (at least 50 percent of activity occurring over one to two days) and "regular" patterns (physical activity distributed more evenly during the week) were associated with similar reductions in the risk of myocardial infarction, stroke, heart failure, and atrial fibrillation compared with inactivity [5]. These findings provide support for recommending exercise whenever it is most feasible for patients and adding regular resistance training. (See "Exercise and fitness in the prevention of atherosclerotic cardiovascular disease", section on 'Type, intensity, and duration of exercise'.)

Iron deficiency and anemia due to daily low-dose aspirin (July 2023)

Aspirin can increase bleeding risk, but data are lacking on anemia and iron deficiency in individuals without clinically obvious bleeding. A new analysis of a randomized trial in older adults assigned to daily low-dose aspirin or placebo has documented a small but statistically significant increase in the rate of anemia (51 per 1000 person-years in the aspirin group versus 43 per 1000 person-years with placebo) and iron deficiency (13 percent with aspirin versus 10 percent with placebo) [6]. While the decision to perform surveillance for anemia or iron deficiency in individuals taking aspirin is individualized, these data provide a rationale for surveillance in those who choose it. (See "Causes and diagnosis of iron deficiency and iron deficiency anemia in adults", section on 'Overview of screening considerations'.)

Cytisinicline for smoking cessation (July 2023)

Cytisinicline (cytisine) is a plant-based alkaloid that has been used for decades for smoking cessation in Central and Eastern Europe. In a multisite randomized trial of 810 individuals who smoked cigarettes daily, continuous abstinence rates up to 24 weeks were higher with 12 weeks of cytisinicline (9 mg total daily dose) compared with placebo (21 versus 5 percent) [7]. A recent meta-analysis also supported use of cytisinicline, which resulted in higher abstinence rates than single-type nicotine replacement therapy [8]. There was a nonsignificant trend toward lower abstinence rates than with varenicline but with fewer side effects (nausea, insomnia, abnormal dreams). These results are promising; however, cytisinicline is not currently available in most countries. (See "Pharmacotherapy for smoking cessation in adults", section on 'Second-line medications'.)

Prevalence of chronic pain in the United States (May 2023)

Chronic pain is one of the most common reasons for patients to seek medical attention and results in high personal and economic costs. A recent Centers for Disease Control and Prevention report estimated that 21 percent of adults in the United States (over 51 million people) had chronic pain in 2021 and 7 percent (17 million) had high-impact chronic pain defined as chronic pain that results in substantial restriction of daily activities [9]. The report also noted a high prevalence among certain populations. For example, over 50 percent of adults with disabilities or poor general health had chronic pain, and at least one-third of these individuals had high-impact chronic pain. The information in this report can inform strategies addressing evaluation and treatment of chronic pain in the United States. (See "Evaluation of chronic non-cancer pain in adults", section on 'Epidemiology and economic impact'.)

FDA warning on selective androgen receptor modulators in some supplements (May 2023)

Selective androgen receptor modulators (SARMs) are found in some supplements labeled as natural testosterone replacements or used for muscle-building. SARMs cannot be legally marketed as dietary supplements in the United States. The US Food and Drug Administration recently issued a consumer warning because of increasing reports of SARM-related adverse events, such as liver injury (predominantly cholestatic) and hallucinations [10]. This warning reinforces our approach to advise patients to avoid pre-workout and muscle-building supplements and to ask patients with unexplained liver injury about supplement use. (See "High-risk dietary supplements: Patient evaluation and counseling", section on 'Anabolic (muscle-building) supplements (higher risk)' and "Hepatotoxicity due to herbal medications and dietary supplements", section on 'Androgenic anabolic steroids'.)

Health benefits of Mediterranean diet in adults at risk of cardiovascular disease (April 2023)

A Mediterranean diet, typically high in fruits, vegetables, whole grains, beans, nuts, and seeds, is thought to have health benefits. In a meta-analysis of 40 trials comparing seven dietary patterns in over 35,000 adults at increased risk of cardiovascular disease (CVD), a Mediterranean diet resulted in lower risk of several outcomes, including all-cause mortality, cardiovascular mortality, stroke, and nonfatal myocardial infarction, when compared with usual care dietary advice [11]. We encourage all patients, especially those at higher risk of CVD, to consume a healthy diet, such as a Mediterranean diet. (See "Healthy diet in adults", section on 'Mediterranean diet'.)

GERIATRICS

Updated Beers criteria for drug prescribing in older adults (July 2023)

The Beers criteria, used to assess inappropriate drug prescribing for older adults, have been updated [12]. Changes in the 2023 criteria include avoidance of: 1) rivaroxaban for long-term treatment of nonvalvular atrial fibrillation or venous thromboembolism, as well as avoidance of warfarin as initial therapy for these conditions unless alternatives are contraindicated; 2) sulfonylureas as first- or second-line monotherapy or add on-therapy; and 3) initiation of oral or transdermal estrogen in older women. The use of aspirin for primary prevention of cardiovascular disease is also discouraged, and deprescribing of aspirin in older patients already taking it for primary prevention is recommended. (See "Drug prescribing for older adults", section on 'Beers criteria'.)

IMMUNIZATIONS

ACIP recommendations for 2023-24 seasonal influenza vaccination (September 2023)

The Advisory Committee on Immunization Practices (ACIP) issued new recommendations for seasonal influenza vaccination in August 2023 (table 1) [13]. The antigenic composition has been updated. In addition, the ACIP now states that egg allergy alone no longer necessitates additional safety measures for influenza vaccination, including with egg-based vaccines, beyond those recommended for any recipient of any vaccine, regardless of severity of previous reaction to egg. All vaccines should be administered in settings where personnel and equipment needed for prompt recognition and treatment of acute hypersensitivity reactions are available. This is consistent with our previous guidance. (See "Seasonal influenza vaccination in adults", section on 'Antigenic composition'.)

Updated COVID-19 mRNA vaccine recommendations (September 2023)

The US Food and Drug Administration and Centers for Disease Control and Prevention have updated COVID-19 vaccine authorizations and recommendations [14,15]. Available mRNA vaccines have been updated to target Omicron variant XBB.1.5 (Moderna COVID-19 vaccine 2023-2024 formula and Pfizer COVID-19 vaccine 2023-2024 formula); bivalent vaccines are no longer available. An updated vaccine is recommended for all individuals aged six months and older. Immunocompetent individuals five years and older should receive one updated vaccine, regardless of prior vaccination history. For individuals who are four years or younger or have an immunocompromising condition (table 2), the number of recommended updated vaccines depends on their vaccination history. Our approach to COVID-19 vaccination is consistent with these recommendations. (See "COVID-19: Vaccines", section on 'Indications and vaccine selection' and "COVID-19: Vaccines", section on 'Benefits of vaccination'.)

SCREENING

Limited role for suicide risk screening (July 2023)

Suicide is the tenth leading cause of death in the United States. Nevertheless, we recommend not routinely screening for suicide risk in adult primary care patients, given lack of evidence that screening reduces suicidal behavior. A systematic review for the United States Preventive Services Task Force found insufficient evidence to determine whether the benefits of screening outweigh the harms in the general population of United States adults (including pregnant and postpartum persons and adults 65 years or older) [16,17]. However, this conclusion did not apply to individuals with existing psychiatric disorders or past histories of suicide attempts; in such patients, standard evaluation includes asking about suicidal ideation and behavior. (See "Suicidal ideation and behavior in adults", section on 'Screening'.)

Screening for anxiety in children and adults (December 2022, Modified July 2023)

Anxiety disorders are common but underrecognized conditions and may cause chronic distress and impaired functioning throughout the lifespan. The United States Preventive Services Task Force now recommends screening for anxiety in all individuals ages 8 to 65 years, including pregnant and postpartum persons [18,19]. These new recommendations are supported by systematic reviews and meta-analyses in both children and adults, documenting that screening tools can accurately identify anxiety disorders and that treatment results in moderate benefits in reducing anxiety and improving disease remission [20,21]. Major harms were not identified. Evidence was insufficient to demonstrate benefits and harms in individuals <8 or >65 years, although screening may also be appropriate in these individuals. Our approach is consistent with these recommendations. (See "Anxiety disorders in children and adolescents: Assessment and diagnosis", section on 'Screening' and "Generalized anxiety disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis", section on 'Screening'.)

Required notification about breast density by the US Food and Drug Administration (April 2023)

Greater breast density may be a risk factor for breast cancer, and dense tissue may interfere with cancer detection. As of 2024, the US Food and Drug Administration will require that mammography facilities notify patients about the density of their breasts [22]. This information should help women with dense breasts talk to their health care provider about their cancer risk, and whether they might benefit from supplemental screening. (See "Breast density and screening for breast cancer", section on 'Legislation in the United States'.)

ADULT CARDIOVASCULAR MEDICINE

Semaglutide in patients with heart failure with preserved ejection fraction and obesity (September 2023)

In patients with heart failure with preserved ejection fraction (HFpEF), weight loss is likely to improve functional status and quality of life, but achieving weight loss in this group of patients is difficult. In a recent trial of more than 500 patients with HFpEF, patients randomly assigned to treatment with semaglutide had greater improvement in exercise capacity (ie, six-minute walk distance), quality of life, and weight loss (-13 percent mean change in body weight versus -2.6 percent) at 52 weeks than patients assigned to placebo [1]. An exploratory analysis suggested a lower risk of urgent HF hospitalizations in those treated with semaglutide. Similar to other patients with obesity, patients with HFpEF and obesity should receive appropriate management to achieve weight loss. (See "Treatment and prognosis of heart failure with preserved ejection fraction", section on 'Obesity'.)

ADULT ENDOCRINOLOGY AND DIABETES

Menopausal symptoms and adverse work outcomes (June 2023)

Hot flashes and other menopausal symptoms are associated with adverse work outcomes (absences, decreased hours, layoffs, firings, and job changes specifically due to menopause symptoms). In a survey study of 4440 menopausal women with moderate symptom scores based upon the Menopause Rating Scale (MRS), 480 (11 percent) reported missing work in the preceding year (average of three days missed) [23]. Women with more severe symptoms (in the highest quartile of MRS scores) were approximately 15 times more likely to have an adverse work outcome than those in the lowest quartile. Based on workdays missed due to menopause symptoms, the authors of the survey study estimated an annual $1.8 billion direct loss to the United States' economy. (See "Clinical manifestations and diagnosis of menopause", section on 'Hot flashes'.)

Levothyroxine dosing in young, healthy adults with primary hypothyroidism (May 2023)

The initial dose of levothyroxine in young, healthy adults with primary hypothyroidism is typically the average full replacement dose, approximately 1.6 mcg/kg body weight per day. However, the range of required doses is broad, depending on the etiology of hypothyroidism and individual patient characteristics. In a retrospective study of post thyroidectomy patients, only 285 of 951 (30 percent) who received initial weight-based dosing of levothyroxine met their thyroid-stimulating hormone (TSH) goal at the first postoperative assessment [24]. A levothyroxine dose calculator based on weight, height, age, sex, and calcium supplementation was able to modestly increase the number of patients meeting their TSH goals (43 percent). Serum TSH should be reevaluated four to six weeks after initiation of levothyroxine and after any dose adjustment; most patients will need one or more dose adjustments before the optimal maintenance dose is identified. (See "Treatment of primary hypothyroidism in adults", section on 'Initial dose'.)

Influence of cortisol assay technique on diagnosis of adrenal insufficiency (May 2023)

The diagnosis of adrenal insufficiency depends on the demonstration of inappropriately low cortisol production. Early morning serum cortisol levels are typically used to exclude the diagnosis of chronic adrenal insufficiency and to select patients for additional evaluation with corticotropin (ACTH) stimulation testing. With newer cortisol assays that use more specific monoclonal antibodies, the morning cortisol threshold to exclude chronic adrenal insufficiency is approximately 25 to 30 percent lower than that used with older immunoassays (eg, 13 to 14 mcg/dL instead of 18 mcg/dL [360 to 390 nmol/L instead of 500 nmol/L]) [25]. When evaluating patients for chronic adrenal insufficiency, the interpretation of the serum cortisol result depends on the type of assay that is used to measure it. (See "Diagnosis of adrenal insufficiency in adults", section on 'Suspected chronic adrenal insufficiency'.)

ADULT GASTROENTEROLOGY

Bariatric surgery for patients with nonalcoholic fatty liver disease and obesity (June 2023)

In a trial of 288 patients with biopsy-proven nonalcoholic steatohepatitis (NASH), gastric bypass or sleeve gastrectomy resulted in higher rates of resolution without worsening fibrosis after one year than lifestyle modification (56, 57, and 16 percent, respectively) [26]. By per-protocol analysis, gastric bypass or sleeve gastrectomy also resulted in higher rates of improvement in fibrosis without worsening NASH (46, 47, and 28 percent, respectively). A large database study comparing bariatric surgery with no surgical intervention in patients with nonalcoholic fatty liver disease (NAFLD) found surgery was associated with lower risks of new-onset heart failure, cardiovascular events, cerebrovascular events, coronary artery interventions, and all-cause mortality at up to seven years follow-up [27]. These data support use of bariatric surgery for patients with NAFLD and obesity who do not achieve weight loss through lifestyle modification. (See "Outcomes of bariatric surgery", section on 'Nonalcoholic fatty liver disease'.)

ADULT HEMATOLOGY AND ONCOLOGY

Updated Beers criteria for anticoagulants (July 2023)

The Beers criteria from the American Geriatric Society are used to determine appropriate drug prescribing in older adults. A 2023 update addressed anticoagulants and the relatively lower bleeding risk with direct oral anticoagulants (DOACs) over warfarin, especially in older individuals [28]. The update recommends that patients ≥65 years of age not initiate warfarin for venous thromboembolism (VTE) or nonvalvular atrial fibrillation unless there are substantial barriers or contraindications to using a DOAC. Among DOACs, apixaban and edoxaban are considered safest. Individuals who have been using warfarin long term with good international normalized ratio (INR) control may reasonably continue warfarin. (See "Warfarin and other VKAs: Dosing and adverse effects", section on 'Older adults'.)

ADULT INFECTIOUS DISEASES

Statins for primary prevention of cardiovascular disease in persons with HIV (September 2023)

HIV infection is associated with an excess risk of cardiovascular disease. A randomized trial evaluated the efficacy of lipid-lowering therapy with pitavastatin for primary prevention in over 7700 persons with HIV ≥40 years of age receiving antiretroviral therapy who had a 10-year atherosclerotic cardiovascular disease (ASCVD) risk score <15 percent [29]. Pitavastatin reduced the relative risk of major cardiovascular events (eg, myocardial infarction, stroke) by 35 percent compared with placebo; the trial was stopped early for this apparent benefit. Based on these data, we now advise statins in all persons ≥40 years of age with an ASCVD score ≥5 percent, particularly if the score is ≥7.5 percent; for those with lower baseline risk, we also discuss statin use, although the absolute benefit is smaller. For persons younger than 40 years of age, our approach is the same as in persons without HIV. (See "Management of cardiovascular risk (including dyslipidemia) in patients with HIV", section on 'Indications for statins'.)

USPSTF 2023 recommendations for tuberculosis infection screening (May 2023)

In May 2023, the United States Preventive Services Task Force (USPSTF) recommended tuberculosis infection (TBI) screening for all adults at increased risk for TBI; this includes individuals from countries with high TB prevalence and individuals in homeless shelters or correctional facilities [30]. The 2023 recommendation is based on evidence review demonstrating that available screening tools for TBI (tuberculin skin test and interferon-gamma release assays) are moderately sensitive and highly specific, and that treatment with available regimens confers moderate net benefit [31]. This guidance is in alignment with the prior (2016) USPSTF recommendation but now emphasizes the potential role of primary care clinicians in screening for and treating TBI infection. (See "Tuberculosis infection (latent tuberculosis) in adults: Approach to diagnosis (screening)", section on 'United States'.)

Expanded recommendations for hepatitis B virus screening in adults (April 2023)

Screening for hepatitis B virus (HBV) in adults has traditionally been recommended for those with risk factors (table 3). In March 2023, the United States Centers for Disease Control and Prevention expanded their recommendations to include universal screening for persons ≥18 years of age at least once during their lifetime, regardless of risk [32]. The rationale is the prevalence of chronic HBV infection in the general population (0.4 percent), the low vaccination rates in adults, and the harms of missed infection such as fulminant hepatitis and liver cancer. Testing should include hepatitis B surface antigen, hepatitis B surface antibody (anti-HB), and total hepatitis B core antibody. We support universal screening; however, screening is generally not needed if an HBV vaccine series has been completed and there is serologic evidence of immunity (anti-HBs ≥10 milli-international units/mL). (See "Hepatitis B virus: Screening and diagnosis in adults", section on 'Individuals without known risk for HBV infection'.)

ADULT NEPHROLOGY AND HYPERTENSION

Social determinants of health and disparities in hypertension control (July 2023)

Among patients treated for hypertension, rates of control are lower in Black individuals as compared with White individuals. As an example, in a large cohort of over 14,000 Black and White adults treated for hypertension, the rate of control (defined as a blood pressure <140/90 mmHg) was 64 percent among Black adults and 75 percent among White adults [33]. Compared with White adults, Black adults had lower annual household incomes and education levels, were less likely to have health insurance, and resided in more economically disadvantaged neighborhoods and regions with a shortage of health professionals; in adjusted analyses, differences in these social determinants accounted for one-third of the racial disparity in hypertension control. Differences in control rates are therefore likely due, at least in part, to social determinants of health. (See "Burden of hypertension in Black individuals", section on 'Control disparity'.)

Kidney effects of different glucose-lowering agents in patients with type 2 diabetes (July 2023)

In prior studies, glucagon-like peptide 1 (GLP-1) receptor agonists reduced albuminuria and slowed estimated glomerular filtration rate (eGFR) decline among patients with diabetic kidney disease, and these agents are therefore used in such patients if additional glucose control is needed. By contrast, in a large trial in over 5000 individuals with type 2 diabetes on metformin monotherapy that directly compared the kidney effects of the GLP-1 receptor agonist liraglutide with a dipeptidyl peptidase 4 inhibitor, insulin, and glimepiride, there were no significant differences among the groups at five years in terms of eGFR decline or development of chronic kidney disease [34]. However, the patients enrolled had normal kidney function and well-controlled blood pressure at baseline, and the number of events was small. Thus, GLP-1 receptor agonists are still appropriate in patients with diabetic kidney disease whose glycated hemoglobin is far from their goal despite therapy with metformin. (See "Treatment of diabetic kidney disease", section on 'Type 2 diabetes: Treat with additional kidney-protective therapy'.)

ADULT NEUROLOGY AND PSYCHIATRY

Aerosolized lidocaine for trigeminal neuralgia exacerbations (June 2023)

Pharmacotherapy for trigeminal neuralgia (TN) typically involves medications to prevent attacks, but limited options are available for patients who also require rescue therapy for acute exacerbations or during titration of preventive therapy. Lidocaine administered intranasally or intraorally as a 2.4 percent aerosol (32 mg per dose) was reported effective in a retrospective study of 152 patients from China with severe TN symptoms [35]. Pain resolution or a 50 percent improvement was reported at 15 and 30 minutes in 78 and 70 percent, respectively. Adverse effects were mild including numbness, bitter taste, and burning in the affected area; no cardiovascular or other systemic adverse effects were reported. Lidocaine nasal sprays are not commercially available in the United States but may be prepared by a compounding pharmacy. These results support the use of aerosolized lidocaine for acute exacerbations of TN. (See "Trigeminal neuralgia", section on 'Rescue therapy'.)

Timing of anticoagulation after acute ischemic stroke (May 2023)

There is no consensus about when to start or resume anticoagulation after acute ischemic stroke in patients with atrial fibrillation (AF). The main concern is that early anticoagulation may increase the risk of intracranial hemorrhage, particularly for large strokes. In the recent ELAN trial of early direct oral anticoagulant (DOAC) therapy (within 48 hours after minor/moderate stroke or on day 6 or 7 after major stroke) versus later DOAC therapy (day 3 or 4 after minor stroke, day 6 or 7 after moderate stroke, or day 12 to 14 after major stroke) in over 2000 patients with AF and acute ischemic stroke, there was a nonsignificant trend towards benefit of early DOAC therapy on the composite primary outcome and on rates of recurrent stroke at 30 and 90 days [36]. Meanwhile, rates of symptomatic intracranial hemorrhage were similar between groups. While not definitive, these findings suggest that early DOAC use is safe and may reduce the risk of recurrent ischemic stroke. (See "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack", section on 'Timing of long-term anticoagulation'.)

Atogepant for chronic migraine prevention (May 2023)

The first oral calcitonin gene-related peptide (CGRP) antagonist has been approved by the US Food and Drug Administration (FDA) for the indication of chronic migraine prevention [37]. In a trial of 778 patients with chronic migraine, atogepant 60 mg once daily or 30 mg twice daily reduced mean monthly headache days more than placebo (-6.9 and -7.5 versus -5.1 days) [38]. The proportion of responders (≥50 percent reduction in headache days per month) was also higher with atogepant (41 and 43 versus 26 percent). We suggest CGRP antagonists such as atogepant as second-line preventive therapy for patients who do not respond to or tolerate first-line therapy. (See "Chronic migraine", section on 'CGRP antagonists'.)

Inaccurate melatonin labeling and unintentional ingestions in young children (May 2023)

Melatonin is widely used for insomnia despite modest effects on sleep, and, as a dietary supplement, it is subject to less stringent regulatory oversight in the United States. Actual quantities of melatonin contained in marketed supplements may vary from what is listed on the label (ranging from 74 to 347 percent of the labeled quantity in one recent study) [39]. Products may also contain substances not listed on the label. As with prescription medications, melatonin should be stored safely in locked containers out of the reach of children. Unintentional pediatric ingestions of melatonin are rising in the United States despite declines in unsupervised medication exposures in young children more generally [40]. (See "Pharmacotherapy for insomnia in adults", section on 'Melatonin' and "Pharmacotherapy for insomnia in children and adolescents: A rational approach", section on 'Melatonin'.)

ADULT PULMONOLOGY

Ensifentrine for moderate-severe COPD (July 2023)

Ensifentrine is a novel inhaled selective dual phosphodiesterase-3 (PDE3) and phosphodiesterase-4 (PDE4) inhibitor with bronchodilator and anti-inflammatory properties. In two concomitant placebo-controlled phase 3 trials totaling approximately 1500 patients with COPD, dyspnea, and moderate-severe airway obstruction, nebulized ensifentrine was well tolerated and improved lung function, dyspnea, and rates of moderate-severe exacerbations compared with placebo [41]. Patients were on a mix of baseline therapies during the trial, but none were receiving dual bronchodilator therapy. Although the optimal strategy for use of this agent requires further study, this first-in-class inhaled bronchodilator/anti-inflammatory agent may, pending regulatory approval, lead to additional therapeutic options for COPD management. (See "Stable COPD: Follow-up pharmacologic management", section on 'Future directions'.)

Mucus plugging on CT scan and COPD mortality (May 2023)

In patients with chronic obstructive pulmonary disease (COPD), excess production and reduced clearance of mucus in the airways lead to an accumulation of occlusive mucus plugs. There is growing evidence that mucus plugging impacts lung function, symptoms, and COPD prognosis. In a study of over 4000 patients with COPD who were evaluated for mucus plugging in medium-to-large airways by high-resolution computed tomography (CT) scan and followed for a median of 9.5 years, higher levels of mucus plugging correlated with increased risk of mortality, even after controlling for other clinical risk factors [42]. It remains to be seen whether therapeutic targeting of these occlusive mucus plugs can favorably impact COPD outcomes. (See "Chronic obstructive pulmonary disease: Prognostic factors and comorbid conditions", section on 'Mucus plugging'.)

GYNECOLOGY

Mifepristone for treatment of adenomyosis (August 2023)

Symptomatic uterine adenomyosis is typically treated with nonsteroidal anti-inflammatory drugs, the 52 mg levonorgestrel-releasing intrauterine device, or surgery, but use of other hormonal medications (eg, oral contraceptive pills, gonadotropin-releasing hormone analogs, mifepristone) has been described. In a randomized trial including over 130 premenopausal patients with adenomyosis based on imaging, mifepristone (10 mg orally daily) resulted in greater improvement in dysmenorrhea, blood loss, and uterine volume compared with placebo after 12 weeks of treatment [43]. Further studies are needed to determine the long-term efficacy of mifepristone in such patients before it can be used routinely for this indication. (See "Uterine adenomyosis", section on 'Alternative hormone strategies'.)

Cabergoline after second-trimester pregnancy loss or termination (June 2023)

Breast symptoms (engorgement, tenderness, milk leakage) after second-trimester pregnancy loss or termination are common, but pharmacotherapy to suppress engorgement and lactation is limited. In a randomized placebo-controlled trial of approximately 70 patients with pregnancy loss or termination at 18 to 26 weeks of gestation, cabergoline (1 mg orally within four hours of fetal expulsion/extraction) substantially reduced breast symptoms on days 2 through 14 of follow-up [44]. Side effects were similar between groups, but the trial was not powered to detect small differences. When counseling patients about breast symptoms after second-trimester pregnancy loss or termination, we discuss the option of cabergoline as well as nonpharmacologic measures (eg, ice, compression with a tight sports bra, avoiding breast stimulation). (See "Overview of second-trimester pregnancy termination", section on 'Postprocedure considerations' and "Overview of the postpartum period: Normal physiology and routine maternal care", section on 'Breast engorgement'.)

Surgical management of incomplete miscarriage (April 2023)

Hysteroscopic resection of retained intrauterine tissue after miscarriage has been proposed as an alternative to vacuum aspiration because it may preserve fertility better. However, a randomized trial comparing the two procedures in 563 patients found similar live birth rates and median times to conception for both procedures at two years' follow-up [45]. Hysteroscopic resection required additional equipment, took longer, and could not be completed in all cases. We continue to use vacuum aspiration to manage patients with retained products of conception. (See "Pregnancy loss (miscarriage): Counseling and comparison of treatment options and discussion of related care", section on 'Surgical management'.)

OBSTETRICS

Respectful, equitable, supportive maternity care (August 2023)

Respectful, equitable, and supportive maternity care is a basic human right that is not always achieved. In a recent survey of mothers in the United States, 90 percent of respondents were satisfied with the care they received during pregnancy, but 20 percent overall reported mistreatment, including requests for help refused or not responded to, physical privacy violated, and verbal abuse [46]. Approximately 30 percent of all respondents and 40 percent of Black, Hispanic, and multiracial respondents reported discrimination during maternity care. Multiple organizations have developed strategies that encourage a culture of respectful, equitable, and supportive maternity care. These strategies can be useful to providers, patients, and health care systems. (See "Prenatal care: Second and third trimesters", section on 'Respectful, equitable, and supportive maternity care'.)

Pessary placement for short cervical length does not reduce preterm birth (July 2023)

Previous meta-analyses of randomized trials comparing use of a cervical pessary versus no pessary (with or without vaginal progesterone) for asymptomatic patients at high risk for preterm birth (PTB) have found that a pessary did not result in a statistically significant reduction in spontaneous PTB; however, the trials had many limitations. In a recent well-designed randomized trial of over 500 patients with cervical length <20 mm, placement of an Arabin pessary at 16 to 23 weeks of gestation also demonstrated no benefit over usual care; the rate of PTB or fetal death <37 weeks was nearly the same for both groups [47]. Strengths of this trial were inclusion of a very high-risk population, exclusion of patients with a history of PTB, and routine use of vaginal progesterone in both groups. These findings further support our practice of not using a pessary to reduce PTB in patients with a short cervix. (See "Cervical insufficiency", section on 'Pessary'.)

Impact of warning signs about cannabis use (June 2023)

The rising prevalence of cannabis use has raised questions regarding best methods of public education about potential risks of use during pregnancy. In a study that surveyed pregnant and recently pregnant women residing in states with legal recreational cannabis, point-of-sale warning signs about risks of cannabis use in pregnancy were not associated with reduced pregnancy use [48]. Although 42 percent of pregnant users agreed that warning signs give important information, 32 percent thought they scare people too much, only 30 percent trusted the information in the signs, and only 26 percent believed signs stop people from using cannabis during pregnancy. This study highlights the need for obstetric providers to provide education about potential risks of cannabis use during pregnancy. (See "Substance use during pregnancy: Overview of selected drugs", section on 'Perceived lack of risk'.)

Early pregnancy diagnosis of gestational diabetes (June 2023)

The benefit of treating gestational diabetes (table 4) diagnosed before 20 weeks of gestation has not been established. In a trial comparing immediate treatment of such patients versus retesting at 24 to 28 weeks and starting treatment at that time if diagnostic criteria are met, immediate treatment did not reduce rates of large-for-gestational age infants or pregnancy-related hypertension [49]. These findings have prompted stakeholders to review their early pregnancy diabetes screening protocols. Treatment of overt diabetes (table 5) diagnosed in early pregnancy is still recommended. (See "Gestational diabetes mellitus: Screening, diagnosis, and prevention", section on 'Management of patients after an early pregnancy GTT'.)

New guidelines on pregnancy/postpartum mental health screening (May 2023)

Updated guidelines from the American College of Obstetricians and Gynecologists now suggest screening patients for depression and anxiety at the initial prenatal visit, later in pregnancy, and at postpartum visits using a standardized, validated tool [50]. Updated guidelines on treatment and management of mental health conditions include screening for bipolar disorder before initiating pharmacotherapy for anxiety or depression, if not previously done [51]. Perinatal Psychiatry Access Programs are a useful resource for obstetric providers managing these patients. (See "Prenatal care: Initial assessment", section on 'History' and "Overview of the postpartum period: Normal physiology and routine maternal care", section on 'Screening'.)

Obstetric outcomes of transgender men (May 2023)

Transgender men are capable of pregnancy, but their obstetric outcomes have not been well studied. A United States database study comparing birth outcomes of nearly 2000 transgender men with 2.7 million cisgender people reported similar rates of severe morbidity and preterm birth for both groups [52]. Transgender men experienced lower rates of cesarean birth despite an overall increased prevalence of chronic medical conditions, anxiety, and depression. While study limitations included potential gender misclassification and a low frequency of severe morbidity, we discuss these reassuring findings with transgender men desiring or experiencing pregnancy. (See "Sexual and gender minority women (lesbian, gay, bisexual, transgender, plus): Medical and reproductive care", section on 'Transgender individuals'.)

Cerclage placement at 24 to 27 weeks of gestation (May 2023)

Cerclage placement at 24 to 28 weeks of gestation is controversial because of concerns that efficacy has not been proven and procedure-related complications may lead to an extremely preterm birth (PTB). In a meta-analysis of individual patient-level data from four randomized trials of cerclage versus no cerclage in 131 singleton pregnancies at 24+0/7 to 26+6/7 weeks of gestation, cerclage did not result in statistically significant reductions in PTB <37, 34, 32, or 28 weeks nor improvement in any neonatal outcome [53]. PTB <37 weeks was not reduced even in subgroups with cervical length ≤15 mm or ≤10 mm. However, confidence intervals were wide, and modest benefits or harms cannot be excluded. In the absence of reassuring data of efficacy and safety, we do not perform cerclage at ≥24 weeks of gestation. (See "Transvaginal cervical cerclage", section on 'Upper and lower gestational age thresholds for cerclage placement'.)

Multicomponent intervention for postpartum hemorrhage (May 2023)

Postpartum hemorrhage (PPH) is a major cause of maternal morbidity and mortality globally. In a randomized trial comparing a multicomponent intervention for PPH versus usual care in nearly 100,000 vaginal births at secondary-level hospitals across Africa, using a calibrated blood-collection drape and a bundle of first-line treatments (eg, uterine massage, uterotonic medications, tranexamic acid) reduced the composite outcome (blood loss ≥1000 mL, laparotomy for bleeding, maternal death from bleeding) by 60 percent (1.6 versus 4.3 percent) [54]. The efficacy of the intervention likely derived from improved detection of PPH coupled with consistent implementation of the evidence-based treatment bundle. Although the trial was conducted in low- and middle-income countries, a similar approach has been suggested for high-income countries. (See "Overview of postpartum hemorrhage", section on 'Early recognition, assessment, and intervention'.)

Biomarker test approved for predicting preeclampsia progression (May 2023)

In stable patients with a hypertensive disorder of pregnancy, it is difficult to predict when severe features of preeclampsia (sFP) will develop. Assessment of the antiangiogenic factor, soluble fms-like tyrosine kinase 1 (sFlt-1), and the proangiogenic factor, placental growth factor (PlGF), in maternal blood may be useful. In the PRAECIS study of hospitalized patients with a hypertensive disorder of pregnancy between 23+0 and 34+6 weeks of gestation, those with sFlt-1:PlGF below the threshold had <5 percent chance of developing sFP within two weeks, while those above the threshold had a 65 percent chance of developing sFP [55]. Based on these findings, in May 2023, the US Food and Drug Administration approved use of the sFlt-1:PlGF test for pregnant patients hospitalized for a hypertensive disorder of pregnancy [56]. Clinicians may find use of this test along with other laboratory tests and clinical assessments helpful for managing these patients. (See "Preeclampsia: Antepartum management and timing of delivery", section on 'Inpatient versus outpatient care'.)

Caffeine consumption and congenital anomalies (May 2023)

The safety of caffeine consumption during pregnancy is an ongoing concern. An update of the 1997-2011 US National Birth Defects Study compared children born with versus without congenital anomalies stratified by maternal self-reported pre- and early pregnancy caffeine intake and found associations with 10 congenital anomalies [57]. However, causality is unlikely given the lack of dose-response relationships, small effect size (odds ratios 1.2 to 1.7), residual confounding, retrospective subjective ascertainment of caffeine consumption, likelihood of chance due to the large number of estimates, and other study limitations. We continue to suggest that individuals who are attempting to conceive or pregnant limit caffeine consumption to less than 200 to 300 mg per day until more conclusive data are available. (See "Caffeine: Effects on reproductive outcomes in females", section on 'Congenital anomalies'.)

Family well-being after gestational carrier pregnancy (April 2023)

Data on child and family psychological well-being after gestational carrier pregnancy has been limited to studies with short-term follow-up. Now, a longitudinal study that administered standardized interviews and questionnaires to 65 mothers and 20-year-old children conceived with assisted reproductive technology (ART), including 22 with gestational carrier pregnancy, reported similar outcomes in young adult psychological adjustment, maternal well-being (measured by anxiety and depression), and couple relationship quality for the ART and 52 unassisted conception groups [58]. This study provides the longest psychological follow-up data of ART families and shows that their well-being, including those who used a gestational carrier, appears to be at least as good as natural conception families. (See "Gestational carrier pregnancy", section on 'Psychological'.)

Race-based differences in screening for substance use in pregnancy (April 2023)

Substance use disorders are an underdiagnosed problem with significant medical implications during pregnancy. In a study that used logistic regression models including race and history of substance use and adjusting for age and other factors, Black patients with a history of substance use had a higher predicted probability of undergoing urine toxicology testing at delivery than comparable White patients, but White patients had a higher predicted probability of a positive test result [59]. This study highlights the need for universal screening of pregnant people for substance use to avoid differential testing for a problem that is known to impact patients of all ages, races/ethnicities, and socioeconomic demographics. (See "Substance use during pregnancy: Screening and prenatal care", section on 'Concerns for bias'.)

Vitamin B12 supplementation does not reduce preterm birth (April 2023)

Cohort studies have reported that lower maternal vitamin B12 levels (particularly gross deficiency) are associated with a higher risk of preterm birth, suggesting that supplementation may improve pregnancy outcome. However, in a placebo-controlled randomized trial of vitamin B12 supplementation during pregnancy conducted in Nepal in which most participants were at least marginally vitamin B12 deficient, supplementation did not improve gestational age at birth or birth weight [60]. For individuals with vitamin B12 deficiency, which is uncommon in the United States, vitamin B12 supplementation is indicated for maternal health. It is administered parenterally if malabsorption is the cause and orally to those with normal absorption. (See "Nutrition in pregnancy: Dietary requirements and supplements", section on 'Vitamin B12'.)

Preventing postpartum overdose (April 2023)

Overdose is a leading cause of pregnancy-related deaths in the year following delivery. In a population-based study of individuals with Medicaid insurance in the United States (2006 to 2013), those with opioid use disorder (OUD) had a high incidence of opioid overdose death compared with the general obstetric population (118 versus 5 per 100,000 deliveries); their all-cause postpartum death rate was also high (316 versus 51 per 100,000 deliveries) [61]. However, postpartum use of medication for OUD (MOUD) was associated with a 60 percent reduction in the odds of opioid overdose death. We follow patients with OUD closely and continue MOUD postpartum to support retention in treatment of OUD and prevent return to use. (See "Opioid use disorder: Overview of treatment during pregnancy", section on 'Continue MOUD'.)

Respiratory syncytial virus vaccination in pregnancy (April 2023)

Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality in infants. In a phase 3 placebo-controlled randomized trial including almost 7000 pregnant people between 24 and 36 weeks of gestation, a single intramuscular injection of RSV prefusion F protein-based vaccine reduced the rate of severe RSV-associated lower respiratory tract illness in infants up to 180 days after birth [62]. The rate of nonsevere RSV-associated illness also trended lower. Rates of preterm birth trended higher in the vaccinated group, but this was not statistically significant. These data suggest effective passive immunity in infants. In August 2023, the US Food and Drug Administration approved the nonadjuvanted recombinant RSV vaccine for pregnant individuals between 32 and 36 weeks of gestation [63]. Recommendations from the United States Centers Disease Control and Prevention and other expert organizations are pending. (See "Immunizations during pregnancy", section on 'Vaccines under investigation'.)

FDA withdraws approval for Makena (April 2023)

In 2002, the US Food and Drug Administration (FDA) approved use of Makena (generic name hydroxyprogesterone caproate) during pregnancy for prevention of recurrent spontaneous preterm birth (sPTB) based on data from a randomized trial, but required a postmarketing trial for confirmation of benefit. In 2023, additional analysis of data from these two trials and other data led the FDA to withdraw its approval of Makena for preventing recurrent sPTB [64]. Pregnant people currently taking Makena may continue or discontinue treatment; the FDA did not identify any harms for either approach. However, medication supply may be limited. Vaginal progesterone does not appear to be an effective alternative for prevention of recurrent PTB; therefore, no pharmacologic prophylaxis is available for this purpose. (See "Progesterone supplementation to reduce the risk of spontaneous preterm labor and birth", section on 'Singleton pregnancy with prior preterm birth'.)

PEDIATRICS: GENERAL PEDIATRICS

Ultrasound guidance for lumbar puncture in children (August 2023)

Previous studies suggest that ultrasound guidance for lumbar puncture (LP) in children increases the chance of success. In a meta-analysis of seven randomized trials (over 700 infants and children), overall LP success rate was higher with ultrasound guidance compared with the use of external landmarks and palpation alone, but the difference was not significant [65]. Subgroup analysis of five studies (over 520 children) demonstrated significantly higher first attempt success in infants undergoing ultrasound guidance, but not in older children. The overall quality of the evidence was considered low. Based on these findings, when performed by a trained provider, ultrasound guidance prior to LP may be useful in infants. Ultrasound guidance in older children is also reasonable, but evidence of benefit in these patients is lacking. (See "Lumbar puncture in children", section on 'Ultrasound guidance'.)

Invasive bacterial illness in febrile young infants with COVID-19 (July 2023)

Evidence is limited for the risk of invasive bacterial illness (IBI) in febrile young infants <60 days old with SARS-CoV-2 infection. In one cohort study of 163 well-appearing febrile infants ≤60 days old (36 neonates) who were diagnosed with COVID-19 by multiplex viral panel testing, none had IBI compared with 0.5 percent of 448 infants with other viral infection (none had meningitis) and 1.3 percent of 320 infants with no viral infection on testing (one with meningitis) [66]. For well-appearing febrile infants ≤60 days old with a positive test for SARS-CoV-2, the risk of IBI appears to be low. For well-appearing infants 29 to 60 days, we suggest, at minimum, urinalysis and urine culture. It is also reasonable to obtain additional studies according to the American Academy of Pediatric Clinical Practice Guideline (algorithm 1). Evidence is insufficient to change the recommended evaluation for well-appearing neonates. (See "The febrile infant (29 to 90 days of age): Outpatient evaluation", section on 'COVID-19' and "The febrile neonate (28 days of age or younger): Outpatient evaluation and initial management", section on 'Well-appearing'.)

Early return to school after concussion in children and adolescents (June 2023)

For the management of pediatric concussion most experts suggest return to school as soon as the patient can tolerate 30 to 45 minutes of concentration, typically within 1 to 2 days of injury. The timing of return to school after concussion and its impact on symptom burden was explored in a prospective cohort study of 1600 children age 5 to 18 years old [67]. For individuals 8 to 18 years old, an early return to school (≤2 days after concussion) was associated with lower symptom burden 14 days after injury, and the association was stronger for individuals with a higher symptom burden at the time of injury. These findings suggest that early return to school may promote more rapid recovery for children with concussion and supports our current approach. (See "Concussion in children and adolescents: Management", section on 'Return to learn'.)

Early return to activity after concussion in children (May 2023)

Evidence continues to grow in support of an early return to activity after a concussion in children. In a meta-analysis of seven randomized trials (269 patients), concussion symptoms resolved more quickly in individuals assigned to early return to subsymptom aerobic activity or multimodal activity (aerobic activity plus visualization and coordination exercise) compared with no prescribed activity [68]. These findings confirm prior studies and support our recommendation that children with concussion undergo a gradual and progressive return to noncontact, supervised, aerobic activity after 24 to 48 hours of physical rest, with details individualized to avoid symptom exacerbation. (See "Concussion in children and adolescents: Management", section on 'Physical rest and activity'.)

Pediatric deaths caused by fentanyl (May 2023)

The opioid epidemic in the United States also affects children; the pediatric mortality rate from prescription and illicit opioids increased by nearly threefold between 1999 and 2016. However, less is known about the impact of the fentanyl crisis on children. A study based on a Centers for Disease Control and Prevention database found that in 2021, fentanyl was implicated in 94 percent of opioid deaths, compared with only 5 percent in 1999; between 2013 and 2021, the pediatric mortality rate from fentanyl increased from 0.05 to 1.97 per 100,000, or 37-fold [69]. Most deaths occurred in adolescents and in the home. These findings support the need for safe storage and prescribing of opioids, increasing parental and adolescent access to opioid use disorder treatment, and widespread access to naloxone in homes. (See "Opioid intoxication in children and adolescents", section on 'Epidemiology'.)

Pediatric poisoning fatalities in the United States (April 2023)

Based on a recent analysis of the United States National Fatality Review-Case Reporting System, fatal pediatric poisoning occurred in just over 700 children ≤5 years old (median age 1 year) over 13 years [70]. In the majority of children, the poisoning was unintentional and happened in the home within sight of supervision (typically a biologic parent). However, deliberate poisoning accounted for 18 percent of deaths. Over one-third of patients had past or current Child Protective Services (CPS) involvement. Opioids were the most commonly implicated substance during the study period and contributed to over half of poisoning deaths in 2018, the last year of the study. These data support harm reduction efforts aimed at preventing fatal pediatric poisoning including clinician and community education on indications and use of naloxone in children and focused poisoning prevention education and social support for children previously or currently involved with CPS. (See "Physical child abuse: Diagnostic evaluation and management", section on 'Toxicology' and "Opioid intoxication in children and adolescents", section on 'Naloxone'.)

Time course of weight gain after adenotonsillectomy for OSA in children (January 2023)

Previous studies have shown a complex relationship between obstructive sleep apnea (OSA), adenotonsillectomy, and weight gain in children. In a randomized trial of early versus delayed adenotonsillectomy in 190 children ages three to five years with mild to moderate OSA, weight gain occurred in the first 12 months after surgery in both groups, but the early intervention group had no further increase in the second postoperative year [71]. These results suggest that postoperative weight gain is time limited and may not represent a new trajectory toward increased risk for obesity. Providers should be aware that children with OSA are at risk for weight gain, regardless of whether they receive adenotonsillectomy, and take steps to minimize or reverse this tendency where possible. (See "Adenotonsillectomy for obstructive sleep apnea in children", section on 'Weight gain'.)

SURGERY

Tonsillectomy for adults with recurrent tonsillitis (June 2023)

Tonsillectomy in adults with recurrent tonsillitis has not been extensively studied. In a trial conducted in the UK enrolling 453 adults with recurrent acute tonsillitis, those who received tonsillectomy had fewer days of sore throat during the subsequent 24 months than those in the conservative management group (median 23 versus 30 days) [72]. We use a shared decision-making approach to tonsillectomy in adults, recognizing that some patients are likely to have positive outcomes, although data are limited. (See "Tonsillectomy in adults: Indications", section on 'Efficacy'.)