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

Diet and healthy aging (April 2025)

Healthy eating is associated with numerous benefits, including reduced mortality and improved quality of life. In a new observational study following over 100,000 patients for up to 30 years, higher intakes of fruits, vegetables, whole grains, unsaturated fats, nuts, legumes, and low-fat dairy were associated with an increased likelihood of healthy aging (defined as surviving to the age of 70 years without major chronic diseases or impairments in cognitive, physical, or mental health), whereas higher intakes of trans fats, sodium, sugary beverages, and red or processed meats were associated with a decreased likelihood of healthy aging [1]. These results are consistent with prior observational studies linking these specific dietary components to health benefits and harms. We continue to promote a healthy diet for all patients, emphasizing the components associated with health benefits and limiting or avoiding those associated with harms. (See "Healthy diet in adults", section on 'Dietary guidelines: Recommended dietary patterns'.)

Intermittent fasting for weight loss (April 2025)

Traditional daily calorie restriction is effective in the treatment of obesity, but long-term adherence can be challenging; intermittent fasting has gained attention as a possible alternative strategy. In a randomized trial of 165 patients with overweight or obesity, intermittent fasting (4:3 fasting; with 80 percent calorie restriction on 3 nonconsecutive days per week and ad-libitum intake on non-fasting days) achieved slightly greater weight loss after 12 months compared with traditional daily caloric restriction [2]. Caloric restriction was greater over the 12-month period with intermittent fasting, suggesting the benefit was due to reduced calorie consumption. We personalize dietary counseling and promote interventions that are most likely to be sustainable for individual patients. (See "Obesity in adults: Dietary therapy", section on 'Intermittent fasting'.)

Sibutramine and sildenafil found in weight loss supplements in France (March 2025)

Weight loss supplements are commonly used worldwide and may contain active ingredients that can cause adverse effects. In 2023, 29 people from France reported using weight loss supplements that were analyzed and found to contain sibutramine and sildenafil [3]. Sibutramine is no longer available by prescription because it increases the risk of stroke and myocardial infarction. Many of the patients in this study reported anorexia, tachycardia, chest pain, increased blood pressure, headaches, and insomnia. These findings support our recommendation to counsel patients not to use weight loss dietary supplements since none are proven safe or effective, and they often contain potentially harmful adulterants. (See "High-risk dietary supplements: Patient evaluation and counseling", section on 'Weight loss supplements'.)

Estimation of free calcium using albumin-adjusted calcium formulas (March 2025)

Albumin-adjusted calcium formulas are often used to estimate free calcium when albumin is abnormal, but none appears to be universally acceptable when compared with ionized calcium. In a new cross-sectional study that included 17,500 patients who had simultaneous testing of albumin, total calcium, and ionized calcium, very few (≤0.3 percent) patients with an albumin <3 g/dL and hypercalcemia by ionized calcium were misclassified as normocalcemic by a commonly used calcium correction formula [4]. However, the formula misclassified 44 percent with hypocalcemia by ionized calcium as normocalcemic, and 6.8 percent with normocalcemia by ionized calcium were misclassified as hypercalcemic. If reliable measurement of ionized calcium is not available, the total calcium may be corrected for any abnormalities in albumin, but the accuracy of the estimate may be poor in a variety of populations. (See "Diagnostic approach to hypercalcemia", section on 'Verify elevated calcium' and "Relation between total and ionized serum calcium concentrations".)

New classifications for patients with obesity (February 2025)

Body mass index (BMI) is increasingly recognized as an inadequate tool to fully capture an individual’s obesity-related health status. A global commission of obesity experts has proposed new strategies to better identify those with increased adiposity and further classify patients based on obesity-related health consequences [5]. One important change is the proposal of new diagnostic categories for "preclinical" and "clinical" obesity. Those with clinical obesity have objectively altered organ function or symptoms related to obesity, whereas those with preclinical obesity have no identifiable health effects from extra weight. These new classifications may help identify those who would benefit most from intensive treatment. We continue to individualize obesity interventions based on overall health status and risk factors for obesity-related morbidity. (See "Obesity in adults: Prevalence, screening, and evaluation", section on 'Preclinical versus clinical obesity'.)

Lenacapavir for prevention of HIV (December 2024)

Antiretroviral pre-exposure prophylaxis (PrEP) is an effective HIV prevention strategy; however, available options are limited by adherence challenges and/or the risk of promoting resistance to first-line HIV regimens should infection occur. Lenacapavir, an HIV-1 capsid inhibitor, is a long-acting agent that had >96 percent efficacy for preventing HIV infection in two randomized, double-blind trials [6,7]. In both, lenacapavir was well tolerated and superior to oral regimens over at least 52 weeks of follow-up. In men and gender-diverse patients who have sex with men, new HIV infections occurred in 2 of 2179 versus 9 of 1086 persons receiving lenacapavir versus oral therapy, respectively. In cisgender women, new HIV infections occurred in 0 of 2134 versus 55 of 3204 persons. Although lenacapavir is not yet approved for use as PrEP in the United States, these data support its future role as an effective agent for HIV prevention. (See "HIV pre-exposure prophylaxis", section on 'Novel approaches to treatment'.)

Semaglutide in patients with moderate to severe knee osteoarthritis (November 2024)

Weight reduction through diet and exercise improves knee osteoarthritis (OA)-related pain in patients with overweight or obesity, but the effect of glucagon-like peptide-1 receptor agonists on knee OA has not been well studied. In a randomized trial in over 400 patients with obesity and moderate or severe knee OA, semaglutide achieved greater reductions in weight and pain scores than placebo, although both groups experienced improvements over the 68-week study period [8]. These data support weight reduction in patients with overweight or obesity and knee OA, and suggest that semaglutide may complement lifestyle changes for these patients. (See "Management of knee osteoarthritis", section on 'Weight loss'.)

Benefits of dietary plant-based fats (November 2024)

Although the optimal diet for cardiovascular health and mortality is not known, increasing evidence highlights the benefits of primarily plant-based diets. In a new prospective cohort study evaluating over 400,000 United States adults for up to 24 years, a greater intake of plant fat, particularly from grains and vegetable oils, was associated with lower overall and cardiovascular mortality [9]. Replacing 5 percent of energy from animal fat with energy from plant fat was associated with a 4 to 24 percent lower risk of all-cause mortality. These results provide additional support for a diet high in healthy unsaturated fat from plants, including fruits, nuts, seeds, vegetables, legumes, whole grains, and plant oils. (See "Dietary fat", section on 'Plant versus animal fat'.)

GERIATRICS

Home-based cardiac rehabilitation for older patients (February 2025)

Home-based cardiac rehabilitation (CR) using portable electronic devices is an attractive alternative to traditional CR; however, its benefits in older adults are unclear. In a study of 400 patients (median age 71 years, range 65 to 91 years), those who were randomly assigned to home-based CR did not experience clinically meaningful improvements in six-minute walk duration (6MWD) or the ability to perform activities of daily living (ADL) compared with those undergoing usual care [10]. Subgroup analysis showed improved 6MWD in female patients and patients who had undergone coronary artery bypass grafting (CABG). These findings suggest that home-based CR may not be effective for most older adults but may benefit certain subgroups; further studies are needed to confirm these results. (See "Cardiac rehabilitation: Indications, efficacy, and safety in patients with coronary artery disease", section on 'Home-based and hybrid cardiac rehabilitation'.)

IMMUNIZATIONS

Pediatric deaths due to influenza-associated encephalopathy or encephalitis (March 2025)

Influenza-associated encephalopathy or encephalitis (IAE) is a rare complication of influenza that can be fatal. New surveillance data from the Centers for Disease Control and Prevention indicate that IAE accounts for a significant proportion of pediatric influenza-associated deaths [11]. Of nearly 1800 influenza-associated pediatric deaths occurring between the 2010-2011 season and the 2023-2024 season, 157 (9 percent) were caused by IAE. Additionally, of the 68 influenza-associated pediatric deaths reported from October 1, 2024 through February 8, 2025, 9 (13 percent) were due to IAE. It is not yet clear whether this represents a higher incidence of IAE this season; however, IAE should be considered in children with influenza and abnormal neurologic findings. (See "Seasonal influenza in children: Clinical features and diagnosis", section on 'Central nervous system'.)

2025 immunization schedules for adults in the United States (February 2025)

The United States Centers for Disease Control and Prevention (CDC) has published the 2025 immunization schedule for adults (figure 1 and figure 2) [12]. Persons 65 years of age or older are now recommended to receive two or more doses of a 2024-2025 COVID-19 vaccine. Pneumococcal vaccine is now recommended for all adults 50 years or older, and the newest conjugate vaccine (PCV21) is now included in the recommendations. Respiratory syncytial virus (RSV) vaccine has a stronger recommendation for persons 75 years or older. Our approach to immunization is largely consistent with these recommendations. (See "Standard immunizations for nonpregnant adults", section on 'Immunization schedule for nonpregnant adults'.)

Egg allergy no longer a concern for any vaccines (February 2025)

Some vaccines contain trace amounts of egg protein (table 1), but none contain enough to cause reactions in egg-allergic patients. For the last several years, it has been recommended that patients not be asked about egg allergy prior to receiving influenza vaccine. More recently, data have accumulated to show that egg allergy is similarly not a concern for administration of the yellow fever vaccine. In the largest study to date, 171 children with egg allergy, including 24 percent with a history of anaphylaxis, underwent skin testing with the yellow fever vaccine and then received it regardless of skin test results, with no allergic reactions [13]. Thus, we no longer inquire about egg allergy prior to the administration of any vaccine. Vaccine providers should remain prepared to treat rare allergic reactions that may occur after any vaccine, but no special precautions are necessary for recipients with egg allergy. (See "Allergic reactions to vaccines", section on 'Hen's egg'.)

RSV vaccination and Guillain-Barré syndrome (January 2025)

In January of 2025, the US Food and Drug Administration issued a warning about Guillain-Barré syndrome (GBS) in persons receiving either of the glycoprotein subunit RSV vaccines [14]. In analyses of observational data from persons ≥65 years, there were an estimated seven excess cases of GBS per million doses of the adjuvanted vaccine (Arexvy) and nine excess cases of GBS per million doses of the bivalent vaccine (Abrysvo). By contrast, RSV disease in adults ≥65 years causes 60,000 to 160,000 hospitalizations and 6000 to 10,000 deaths annually. This information is important for patients considering RSV vaccination, with decisions tailored to individualized risk assessment for severe RSV disease (table 2). (See "Respiratory syncytial virus infection in adults", section on 'Risk of Guillain Barré'.)

2025 immunization schedule for infants, children, and adolescents published by the CDC (December 2024)

The United States Centers for Disease Control and Prevention has provided the 2025 updates for the routine immunization schedules for infants, children, and adolescents ≤18 years of age [15]. Notable changes in the 2025 schedules include an additional dose of COVID-19 vaccine for moderately or severely immunocompromised individuals and the addition of Vaxelis to PedvaxHIB as a preferred Hib vaccine for American Indian and Alaska Native infants. (See "Standard immunizations for children and adolescents: Overview", section on 'Routine schedule'.)

Lower age cutoff for pneumococcal vaccine indications (November 2024)

In October 2024, the United States Advisory Committee (ACIP) extended pneumococcal vaccination recommendations to include all adults ≥50 years of age, regardless of risk factors (table 3) [16]. Previously, the age threshold was ≥65 years for healthy adults and ≥19 years for those at risk for pneumococcal infection or severe complications from pneumococcal infection. This decision is based on knowledge that the incidence of pneumococcal disease starts to increase at age 50 (table 4) and the predicted reduction in invasive pneumococcal disease cases in certain underrepresented ethnic/racial groups within the United States. We agree with the new guidelines from the ACIP and now suggest pneumococcal vaccination beginning at age 50 for all adults. (See "Pneumococcal vaccination in adults", section on 'Indications for vaccination'.)

RSV vaccine effective in mild to moderately immunocompromised individuals (October 2024)

The respiratory syncytial virus (RSV) vaccine is recommended for immunocompromised individuals aged 60 and above, although the data on the efficacy of the RSV vaccine in this population is limited. In an electronic health records-based observational study that included over 10,000 predominantly mild to moderately immunocompromised individuals ≥60 years old (46 percent of whom had a malignancy), the adjusted RSV vaccine effectiveness against respiratory virus-associated hospitalizations in the first year of follow-up was 73 percent [17]. This study provides preliminary evidence of vaccine efficacy in this patient population and supports vaccination against RSV in immunocompromised individuals aged 60 and above. (See "Immunizations in adults with cancer", section on 'Respiratory syncytial virus (RSV)'.)

Electronic letters to improve influenza vaccination rates (October 2024)

Electronic letters have been proposed to improve annual influenza vaccination rates. In a study including more than 300,000 Danish patients aged 18 to 64 years with chronic diseases, influenza vaccination rates were higher among those randomly assigned to receive one of six letters that included a behavioral nudge compared with those who received no letter (40 versus 28 percent) [18]. The largest effect sizes were observed with a repeat letter sent 10 days after the initial letter (42 percent) and a letter emphasizing potential cardiovascular benefits of vaccination (40 percent). Electronic letters are scalable, cost-effective, and may have beneficial public health implications. (See "Seasonal influenza vaccination in adults", section on 'Improving vaccination rates'.)

SCREENING

Colonoscopy or fecal immunochemical testing for colorectal cancer screening (April 2025)

Screening for colorectal cancer (CRC) reduces CRC deaths, but comparative data between available screening tests are limited. In a population-based, randomized trial of over 57,000 adults at average risk for CRC, the risk of CRC mortality was similar among those screened by fecal immunochemical test (FIT) versus colonoscopy (0.24 versus 0.22 percent at 10 years) [19]. Participation in any form of CRC screening was higher in the group randomized to FIT (40 versus 32 percent). For adults at average risk of CRC, colonoscopy every 10 years or FIT every one to three years are our preferred screening strategies. (See "Screening for colorectal cancer: Strategies in patients at average risk", section on 'Test selection'.)

Prostate-specific antigen values in transgender women receiving estrogen (November 2024)

Gender-affirming hormone therapy for transgender women reduces prostate-specific antigen (PSA) levels; however, the magnitude of this effect is unknown. In a retrospective study of 210 transgender women receiving estrogen, the median PSA was 0.02 ng/mL [20]. Thirty-six percent of patients had undetectable PSA values. By comparison, the median PSA in similar-age cisgender male patients without known prostate cancer has historically been reported as 1.0 ng/mL. These findings suggest PSA may be falsely low in transgender women receiving estrogen. The role of PSA for prostate cancer screening in this population is an area requiring further study. (See "Measurement of prostate-specific antigen", section on 'Medications'.)

ADULT CARDIOVASCULAR MEDICINE

Intravenous iron supplementation in heart failure (April 2025)

In patients with heart failure (HF) with reduced ejection fraction (HFrEF), iron supplementation reduces the risk of readmissions, but whether sustained iron therapy has additional beneficial effects remains uncertain. In a trial in more than 1100 patients with HFrEF, New York Heart Association class II or III HF symptoms, and iron deficiency who were treated for up to three years with ferric carboxymaltose or placebo, there were similar rates of mortality and HF hospitalizations between the groups [21]. Subgroup analyses, including an analysis by transferrin saturation (ie, 20 percent cutoff), showed similar findings to the main trial results. Despite the results of this trial, patients with HF who have iron deficiency with or without anemia should receive iron and should be evaluated for the cause of the deficiency. (See "Evaluation and management of anemia and iron deficiency in adults with heart failure", section on 'Iron supplementation'.)

Bleeding risk with direct oral anticoagulants (March 2025)

Direct oral anticoagulants (DOACs) are often preferred to warfarin since they do not require routine monitoring, but bleeding risks are uncertain. A new meta-analysis of data from randomized trials involving over 26,000 individuals prescribed a DOAC or low-dose aspirin reported that bleeding risks with DOACs were similar to low-dose aspirin, which carries a small increased risk [22]. However, clinicians should use caution when comparing bleeding risks between DOACs from different trials, as trial populations may differ and data from direct comparisons are limited. (See "Risks and prevention of bleeding with oral anticoagulants", section on 'Drug class'.)

Ischemic events in giant cell arteritis (February 2025)

Which patients with giant cell arteritis (GCA) may be at highest risk for cranial ischemic events (CIC) is not clear. In a multicenter consortium database study of over 1,900 patients with GCA, 17 percent had CIC (eg, blindness, stroke) [23]. Risk factors for CIC included age at diagnosis and hypertension, whereas anticoagulation (but not antiplatelet agents such as aspirin) was associated with lower risk. This study suggests that traditional cardiovascular risk factors may be associated with CIC in patients with GCA, but whether anticoagulation is protective requires further study and prospective validation. (See "Clinical manifestations of giant cell arteritis", section on 'Risk factors'.)

Effects of exercise on lipoproteins (February 2025)

Although numerous randomized trials document the benefits of exercise on serum lipid profiles, few analyses have compared the effects of different types of exercise on specific lipoproteins. In a meta-analysis of 148 randomized trials, exercise modestly improved total, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) cholesterol and triglyceride levels, with changes that ranged from 3.5 to 11.7 percent [24]. Interventions combining aerobic and resistance exercise produced optimal reductions in serum lipoproteins. On meta-regression, each extra weekly aerobic session reduced total cholesterol by 7.68 mg/dL (0.2 mmol/L). These results provide important guidance for counseling patients on the benefits of exercise on lipid profiles. (See "Effects of exercise on lipoproteins and hemostatic factors", section on 'Type of exercise'.)

Colchicine after acute myocardial infarction (January 2025)

The efficacy of colchicine for prevention of recurrent myocardial infarction (MI) remains unclear. One previous trial in patients with MI found that colchicine decreased the rate of a composite cardiovascular endpoint compared with placebo, but this effect was largely driven by lower rates of angina and stroke; rates of mortality and recurrent MI were similar. In a more recent trial in over 7000 patients with acute MI, rates of death, recurrent MI, and stroke were comparable among patients treated with colchicine or placebo over a median of three years [25]. In patients with acute MI, we do not routinely treat with colchicine for secondary prevention of cardiovascular events. (See "Overview of the nonacute management of ST-elevation myocardial infarction", section on 'Colchicine'.)

Duration of beta blocker therapy after acute myocardial infarction (December 2024)

Most patients with a myocardial infarction (MI) are treated with a beta blocker indefinitely, although this practice is based on data obtained prior to modern advances in MI management such as stenting, dual antiplatelet therapy, and statin therapy. In a recent trial in nearly 3700 patients with a history of acute MI who had already received beta blocker therapy for at least six months (median 2.9 years) and had no other indication for beta blocker therapy (eg, reduced left ventricular systolic function), patients randomly assigned to discontinue beta blocker therapy had similar rates of mortality and recurrent MI after four years compared with those who continued such therapy [26]. Quality-of-life scores were also similar between the groups, suggesting that discontinuing beta blocker therapy did not noticeably impact quality of life. For patients treated with a beta blocker for at least three years after MI and who have no other indication to continue a beta blocker, clinicians should discuss the potential benefits and risks of continued therapy. (See "Acute myocardial infarction: Role of beta blocker therapy", section on 'Duration'.)

Choice of management strategy in older patients with non-ST-segment elevation myocardial infarction (December 2024)

In patients with non-ST-segment elevation myocardial infarction (NSTEMI), the approach to management typically includes early coronary angiography and appropriate percutaneous coronary intervention (PCI), but the efficacy and safety of this approach in older patients are unclear. In a recent trial in over 1500 patients ≥75 years old with NSTEMI, patients randomly assigned to an invasive management strategy (ie, coronary angiography and PCI) had a lower rate of recurrent myocardial infarction but a similar rate of all-cause death when compared with those assigned to a conservative management strategy [27]. The rate of non-fatal bleeding was not significantly higher in the invasive management group. In patients with NSTEMI, we suggest invasive coronary angiography rather than other management strategies. (See "Non-ST-elevation acute coronary syndromes: Selecting a management strategy", section on 'Evidence of infarction (NSTEMI)'.)

Timing of anticoagulation after acute ischemic stroke in patients with atrial fibrillation (November 2024)

The timing of anticoagulation after acute ischemic stroke in patients with atrial fibrillation (AF) is controversial. Because of concern for intracranial hemorrhage, the start of anticoagulation is often delayed by one to two weeks for certain patients, such as those with large infarcts. However, recent findings from the OPTIMAS randomized trial and the CATALYST meta-analysis challenge this approach [28-30]. In a meta-analysis of patient-level data on over 6700 patients from trials (including OPTIMAS) evaluating the timing of direct oral anticoagulant (DOAC) initiation in patients with stroke and AF, rates of symptomatic intracranial hemorrhage were similarly low for both early (≤4 days from stroke onset) and late (≥5 days) DOAC administration, and the composite outcome of stroke or hemorrhage with early initiation was marginally lower at 30 but not 90 days [29]. Approximately 15 percent of patients had large or severe infarcts in the three largest trials. These data support the safety of early DOAC administration in patients with AF and ischemic stroke, but whether earlier DOAC treatment reduces the risk of recurrent ischemic stroke remains to be settled. (See "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack", section on 'Timing of anticoagulation after acute ischemic stroke or TIA in patients with atrial fibrillation'.)

Efficacy of catheter ablation for atrial fibrillation (November 2024)

Catheter ablation (CA) for atrial fibrillation (AF) improves AF symptoms in most patients, but AF commonly recurs and anticoagulation is commonly required to mitigate the risk of stroke associated with AF. These issues were illustrated by a double-blind trial in which over 120 patients with symptomatic AF were randomly assigned to undergo either CA or a sham procedure [31]. At six months, the CA group had greater improvement in AF symptoms and greater reduction in frequency of AF than the sham group, although AF was common in both groups. These findings inform decisions regarding CA for AF as well as the approach to monitoring and anticoagulation after the procedure. (See "Atrial fibrillation: Catheter ablation", section on 'Effect on symptoms and AF burden'.)

ADULT DERMATOLOGY

Topical roflumilast for atopic dermatitis (February 2025)

Roflumilast is a selective, highly potent phosphodiesterase-4 inhibitor with anti-inflammatory properties. In two identical randomized trials including over 1300 patients with mild or moderate atopic dermatitis (AD), more patients assigned to roflumilast cream 0.15% once daily achieved the primary endpoint of Investigator Global Assessment (IGA) clear/almost clear at four weeks compared with those assigned to a vehicle control [32]. Treatment-emergent adverse effects were mild or moderate and included headache, nausea, application site pain, and nasopharyngitis. Based on these data, topical roflumilast cream 0.15% was approved by the United States Food and Drug Administration for the treatment of mild to moderate AD in adults and children ≥6 years. (See "Treatment of atopic dermatitis (eczema)", section on 'Topical roflumilast'.)

Antileukotriene drugs minimally helpful in chronic spontaneous urticaria (November 2024)

The benefit of adding a leukotriene receptor antagonist (LTRA) such as montelukast for patients with chronic spontaneous urticaria that is not controlled with antihistamines alone has not been clear. In a new meta-analysis of 34 randomized trials including over 3000 children and adults, the efficacy of a LTRA added to a nonsedating antihistamine at standard dose was compared with antihistamine alone [33]. The addition of LTRAs provided some benefit, but the degree of improvement on the Urticaria Activity Score was just 5 points, which was less than half of the minimally important difference of 11 points for the symptom scale used. Based upon these findings, we do not advocate for the use of LTRAs in the routine management of chronic spontaneous urticaria. (See "Chronic spontaneous urticaria: Standard management and patient education", section on 'Leukotriene modifiers'.)

ADULT ENDOCRINOLOGY AND DIABETES

Automated insulin delivery in adults with type 2 diabetes (March 2025)

Automated insulin delivery (AID) systems are often used to treat type 1 diabetes, but few studies have evaluated their use in type 2 diabetes. In a 13-week trial, 319 adults with type 2 diabetes (mean age 58 years, mean A1C 8.2 percent) were randomly assigned to treatment with AID (n = 215) or their usual insulin delivery strategy (predominantly multiple daily injections [MDI]; n = 104) [34]. AID use led to a greater reduction in mean A1C (-0.9 versus -0.3 percentage points with usual care) and a greater increase in time spent in the target glucose range (70 to 180 mg/dL [3.9 to 10 mmol/L]). The rate of hypoglycemia was low in both groups. These findings support the utility of AID in adults with type 2 diabetes who are not meeting glycemic goals with MDI insulin regimens. (See "Continuous subcutaneous insulin infusion (insulin pump)", section on 'Patient selection'.)

Accelerated bone loss in older men with type 2 diabetes (February 2025)

In people with type 2 diabetes, fracture risk is elevated despite normal or increased bone mineral density (BMD). In an analysis of 4095 older men (mean age approximately 73 years) in whom BMD at the total hip was measured at baseline and after a mean of 4.6 years, those with type 2 diabetes (n = 578) exhibited a greater decline in BMD than those with normoglycemia (n = 1993; mean decrease -2.23 versus -1.57 percent, respectively) [35]. Accelerated bone loss was evident despite higher mean baseline BMD at the hip among men with diabetes. These findings suggest that accelerated bone loss may contribute to fracture risk in people with type 2 diabetes. (See "Bone disease in diabetes mellitus", section on 'Bone quantity and quality'.)

Extended-interval dosing for zoledronic acid in postmenopausal women with low bone mass (February 2025)

In postmenopausal women with low bone mass, zoledronic acid administered every one to two years increases bone mineral density. The clinical efficacy of a longer dosing interval was evaluated in a 10-year trial of zoledronic acid (5 mg IV once at baseline only or once at baseline and again at five years) versus placebo in 1054 early postmenopausal women (mean age 56 years) with T-scores >-2.5 and <0.0 [36]. Participants who received one or two doses of zoledronic acid had a lower incidence of morphometric vertebral fracture compared with those who received placebo. Both zoledronic acid regimens also reduced risk of major osteoporotic fracture. Extended dosing intervals for zoledronic acid may help reduce treatment burden for postmenopausal women who opt for pharmacotherapy to prevent osteoporosis. (See "Overview of the management of low bone mass and osteoporosis in postmenopausal women", section on 'Options for pharmacotherapy'.)

Age-related increase in upper reference limit for TSH (January 2025)

Although a growing number of studies have reported an age-related increase in the upper reference limit for thyroid stimulating hormone (TSH), few laboratories provide age-specific reference ranges for adults. In a recent multicenter, retrospective study (7.6 million TSH samples), the upper reference limit for TSH increased starting at age 50 years in females and 60 years in males [37]. The upper reference limit for an individual 70 to 80 years old ranged from 5.0 to 6.2 mU/L, depending on assay, with the reported upper limit ranging from 4.1 to 4.8 mU/L. If age-adjusted normal ranges for TSH were employed, there would be a decrease in the diagnosis of subclinical hypothyroidism in adults >50 to 60 years of age; we favor using age-based normal ranges for TSH. (See "Laboratory assessment of thyroid function", section on 'Serum TSH'.)

Diabetic neuroarthropathy risk factors (January 2025)

Risk factors for diabetic neuroarthropathy (ie, Charcot foot) include repeated trauma, foot ulceration, and infection or surgery of the affected foot. A retrospective study of 3400 patients with diabetic neuroarthropathy (and 27,000 patients with diabetes alone) identified additional risk factors for diabetic neuroarthropathy, including atherosclerosis, macroalbuminuria, microalbuminuria, and retinopathy, both in patients with type 1 and type 2 diabetes [38]. These data suggest that patients with atherosclerosis and/or microvascular complications of diabetes mellitus may benefit from screening for diabetic neuroarthropathy. (See "Diabetic neuroarthropathy", section on 'Epidemiology and risk factors'.)

ADULT GASTROENTEROLOGY

Treatment of Helicobacter pylori infection in adults (November 2024)

Over half of individuals in the United States with Helicobacter pylori infection continue to receive clarithromycin-based treatment regimens, despite rising rates of H. pylori resistance to clarithromycin and declining rates of treatment success with these regimens [39]. Recent guidelines from the American College of Gastroenterology reinforce the importance of using non-clarithromycin-based regimens for the initial and salvage treatment of H. pylori infection [40]. Preferred regimens for the empiric management of H. pylori infection in treatment-naïve adults include optimized bismuth quadruple therapy, rifabutin triple therapy, and vonoprazan-amoxicillin dual therapy. The guidelines also emphasize testing to confirm H. pylori eradication after treatment and discuss the role of antimicrobial susceptibility testing in H. pylori management. Based on available evidence, we suggest optimized bismuth quadruple therapy as the preferred regimen for H. pylori infection in treatment-naïve adults. (See "Treatment of Helicobacter pylori infection in adults".)

ADULT HEMATOLOGY AND ONCOLOGY

Frequency of mammographic surveillance in patients aged ≥50 years with breast cancer (February 2025)

There are limited data regarding the frequency of mammographic surveillance in breast cancer survivors. In a randomized trial in 5235 patients age ≥50 years with a history of breast cancer, annual versus less frequent mammographic surveillance resulted in similar five-year breast cancer-specific survival rates (98.1 versus 98.3 percent) and overall survival rates (94.7 versus 94.5 percent) [41]. Most breast cancer events in both groups were detected from emergency admissions or referrals for symptoms. Although these results are promising, the follow-up for this trial was short. The majority of patients (83 percent) had estrogen receptor-positive disease, which often recurs later. We await further data before altering our practice related to frequency of mammographic screening of breast cancer survivors. (See "Approach to the patient following treatment for breast cancer", section on 'Mammography'.)

Increased risk of pulmonary embolism in sickle cell trait (December 2024)

Sickle cell trait is an asymptomatic carrier state, but risks are increased for certain complications. A new study used genetic data from almost four million individuals to assess risks for venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT) [42]. Compared to individuals without sickle cell trait, those with sickle cell trait had an approximately 2-fold increased risk for PE; a definite increased risk for DVT was not identified, and the overall VTE risk was increased 1.5-fold. This VTE risk for sickle cell trait was less than that for factor V Leiden (3.3-fold) and is not great enough to warrant management changes. Appropriate VTE prophylaxis during hospitalization should be emphasized. (See "Sickle cell trait", section on 'Venous thromboembolism'.)

Carrier screening for hemophilia (December 2024)

Hemophilia A and B are X-linked conditions. Daughters of affected males are obligate carriers, and mothers of affected males are often carriers (some cases arise de novo). Carriers are typically asymptomatic, but they may require additional interventions during hemostatic challenges (surgery, delivery of a child), and their children may be affected. A new study illustrated the lack of comprehensive carrier screening in 287 kindreds followed in a single hemophilia treatment center [43]. Of 900 females screened, 454 were obligate or genetically proven carriers, but 328 had yet to undergo genetic testing, and 59 obligate carriers had yet to have their factor activity level measured. This study highlights the importance of testing female first-degree relatives of individuals with hemophilia. (See "Clinical manifestations and diagnosis of hemophilia A and B", section on 'Carrier detection'.)

ADULT INFECTIOUS DISEASES

Updated IAS-USA guidelines for the treatment and prevention of HIV (February 2025)

In December of 2024, the International Antiviral Society-USA guideline panel released updated guidelines on the treatment and prevention of HIV [44]. They reaffirmed their preference for an initial regimen that includes dolutegravir or bictegravir combined with tenofovir-emtricitabine or lamivudine. Protease inhibitor-containing regimens are typically reserved for patients with suspected or confirmed resistance to integrase strand transfer inhibitors, such as those who acquire HIV while receiving cabotegravir as pre-exposure prophylaxis. Antiretroviral therapy (ART) should be initiated as soon as possible. When one of the preferred three drug regimens is used, ART can be started before the results of baseline testing return. (See "Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach", section on 'Approach for most patients'.)

Recombinant hepatitis B vaccine (Heplisav-B) during pregnancy. (December 2024)

Hepatitis B vaccination may be warranted during pregnancy for selected patients (eg, those at high risk of acquiring hepatitis B virus). In December 2024, the Advisory Committee on Immunization Practices endorsed the US Food and Drug Administration approval of the adjuvanted recombinant vaccine (Heplisav-B) for use in pregnancy [45]. In an unpublished observational study that included 75 pregnant patients who received the adjuvanted recombinant vaccine during the 28 days before conception or during pregnancy, no major birth defects were identified nor was there an increased rate of pregnancy loss. This approval expands the list of hepatitis B vaccines that are approved for use during pregnancy. (See "Immunizations during pregnancy", section on 'Hepatitis B'.)

Lithium aspartate ineffective for neurocognitive effects of long COVID (November 2024)

Anecdotal reports have suggested a benefit from low-dose lithium in patients with neurocognitive symptoms due to long COVID. However, in a placebo-controlled randomized trial in 52 patients with at least four weeks of neurocognitive symptoms following COVID-19 infection, three weeks of lithium aspartate (10 to 15 mg daily) failed to improve fatigue or cognitive dysfunction scores [46]. Limitations included small sample size and possible under-dosing. While low-dose lithium does not appear to benefit patients with long COVID-associated neurocognitive symptoms, further exploratory studies may be warranted. (See "COVID-19: Management of adults with persistent symptoms following acute illness ("long COVID")", section on 'Investigational therapies'.)

ADULT NEPHROLOGY AND HYPERTENSION

Updated microscopic hematuria guidelines from the American Urologic Association (March 2025)

The American Urologic Association (AUA) has released a 2025 update to its guidelines for the diagnosis, evaluation, and follow-up of microscopic hematuria [47]. The amended guidelines include a revised risk stratification system and risk-based evaluation algorithm as well as updated guidance on the use of urine-based tumor markers and cytology. Our approach to the evaluation of microscopic hematuria in adults is largely consistent with these revised guidelines. (See "Evaluation of hematuria in adults", section on 'Asymptomatic patients'.)

Blood pressure measurement using a cuffless blood pressure device (March 2025)

The diagnosis and management of hypertension is based on standardized blood pressure (BP) measurement using cuff-based BP monitors, but studies are evaluating the accuracy of cuffless devices that estimate BP indirectly through measurements of photoplethysmography, pulse wave analysis, and other techniques. In a single-center observational study of 51 patients, the seven-day average daytime systolic BP obtained from the cuffless monitor was similar to that obtained by 24-hour ambulatory blood pressure monitoring (ABPM) [48]. However, the cuffless BP device consistently reported higher nocturnal systolic and diastolic BP compared with ABPM (mean difference 12.5 mmHg and 4.1 mmHg, respectively). Further validation and specific implementation guidelines are needed before cuffless devices can be recommended for clinical use. (See "Hypertension in adults: Blood pressure measurement and diagnosis", section on 'Cuffless blood pressure monitors'.)

Association of hyponatremia correction rates with in-hospital mortality (December 2024)

In patients with severe, chronic hyponatremia (ie, serum sodium <120 mEq/L), the goal of initial therapy is to raise the serum sodium level slowly to avoid overcorrection. This recommendation was challenged by a meta-analysis of retrospective cohort studies that found that rapid correction of severe hyponatremia in hospitalized patients was associated with lower in-hospital mortality compared with slow correction [49]. However, the major limitation of this study is its analysis of all-cause in-hospital mortality rather than death from cerebral edema (the cause of death potentially caused by slower correction). Thus, the findings were likely confounded by the fact that severely ill patients, who are at high risk for in-hospital mortality, have hyponatremia that is more recalcitrant and less likely to correct without hypertonic saline; conversely, patients with acute hyponatremia or less severe underlying disease (and a lower risk of in-hospital mortality) are more likely to correct quickly when the cause of hyponatremia is eliminated. We continue to suggest slow correction in patients with severe, chronic hyponatremia. (See "Overview of the treatment of hyponatremia in adults", section on 'Goal rate of correction'.)

ADULT NEUROLOGY AND PSYCHIATRY

Surgical outcomes in cervical radiculopathy may depend on underlying cause (April 2025)

The benefits of surgery for the treatment of cervical radiculopathy have not been well established, and the role of the underlying compressive mechanism in surgical outcomes is uncertain. In a single-center study comprising two randomized trials of patients with cervical disc herniation (n = 89) or degenerative spondylosis (n = 91), patients with disc herniation assigned to anterior cervical discectomy and fusion had modestly better self-reported scores on the neck disability index (NDI) scale at 12 months than those who received nonoperative care [50]. Outcomes for patients with spondylosis were similar among surgical and nonsurgical groups. One patient undergoing surgery developed recurrent laryngeal nerve injury and another reported transient postoperative dysphonia. These results suggest the underlying mechanism may impact the benefits of surgery in cervical radiculopathy. (See "Treatment and prognosis of cervical radiculopathy", section on 'Evidence of efficacy'.)

Competing risks when resuming direct oral anticoagulants after intracerebral hemorrhage (March 2025)

Patients with atrial fibrillation and intracerebral hemorrhage (ICH) often have long-term competing risks of ischemic stroke and recurrent ICH. Limited data are available to help quantify these risks in patients taking direct oral anticoagulants (DOACs). In an open-label trial of 319 patients with prior ICH and atrial fibrillation who were randomly assigned to treatment with a DOAC or withholding anticoagulation, the subsequent ischemic stroke rate was lower in those assigned to a DOAC (0.8 versus 8.6 per 100 patient-years), but this benefit was partially offset by an increase in ICH recurrence (5 versus 0.8 per 100 patient-years) [51]. All-cause mortality was similar between groups, with wide confidence intervals. These data support the feasibility of resuming anticoagulation with a DOAC in selected patients with ICH but highlight the importance of shared decision-making incorporating these competing risks. (See "Spontaneous intracerebral hemorrhage: Secondary prevention and long-term prognosis", section on 'Therapeutic options'.)

Treatment retention in opioid use disorder (February 2025)

Data from randomized trials suggest that in individuals with opioid use disorder (OUD), treatment retention is higher with methadone than buprenorphine-naloxone. However, many of these trials were conducted in selected populations before the widespread use of potent synthetic opioids, such as fentanyl. In a recent population-based cohort study including nearly 31,000 individuals initiating treatment for OUD, rates of treatment discontinuation were higher among recipients of buprenorphine-naloxone than methadone (89 versus 82 percent) [52]. Among participants who reached optimal medication doses, discontinuation rates continued to favor methadone (42 versus 31 percent), and these results were consistent after the introduction of fentanyl. This study reinforces prior evidence supporting greater treatment retention with methadone than buprenorphine-naloxone, even in populations using fentanyl. (See "Opioid use disorder: Treatment overview", section on 'Use of buprenorphine or methadone'.)

Semaglutide for alcohol use disorder (February 2025)

Preliminary findings from cohort studies suggest that semaglutide, a glucagon-like peptide-1 receptor agonist, may reduce alcohol cravings and alcohol use. In a randomized trial including 48 participants with alcohol use disorder, nine weeks of subcutaneous semaglutide (doses from 0.25 mg to 1 mg weekly) reduced weekly alcohol cravings and the number of heavy drinking days (by approximately one day per week) compared with placebo [53]. These results suggest a potential role for semaglutide in the management of alcohol use disorder and justify the need for larger trials. (See "Alcohol use disorder: Pharmacologic management", section on 'Therapies with unclear efficacy'.)

Masked taper for discontinuing benzodiazepines (December 2024)

For individuals who need to discontinue chronic benzodiazepines, the optimal tapering strategy to minimize withdrawal symptoms is unclear. In a recent randomized trial of 188 older adults with insomnia, a masked taper over nine weeks (ie, benzodiazepine pills with progressively increasing inert filler) plus augmented cognitive-behavioral therapy for insomnia (CBT-I, with exercises targeting expectations about the taper and placebo effects) increased the rate of benzodiazepine discontinuation at six months compared with an unmasked taper plus standard CBT-I (73 versus 59 percent) [54]. Although the results suggest that blinding patients to the taper rate may help improve benzodiazepine discontinuation, participants took relatively low doses at baseline (4 mg diazepam equivalents); thus, the efficacy of this strategy in other populations using higher doses, as in benzodiazepine use disorder, is uncertain. (See "Benzodiazepine use disorder", section on 'Taper rate'.)

Timing of resumption of antiplatelet therapy after intracerebral hemorrhage (December 2024)

Antiplatelet therapy in patients with established atherosclerotic disease who develop intracerebral hemorrhage (ICH) is often resumed to reduce the risk of early ischemic complications, but the optimal time for safe resumption is uncertain. In a multicenter clinical trial that included 269 patients from China with acute nontraumatic ICH and atherosclerotic risk factors who underwent hematoma evacuation, the rate of new ischemic cerebral, cardiac, or peripheral vascular events within 90 days was lower in patients assigned to start aspirin on the third day following surgery than in those assigned to start aspirin 30 days after surgery (20 versus 31 percent) [55]. Intracranial hemorrhage was rare, occurring in one patient in the early aspirin group and four patients in the late group. These results support our preference for early resumption of antiplatelet therapy after ICH in patients with atherosclerotic disease. (See "Spontaneous intracerebral hemorrhage: Secondary prevention and long-term prognosis", section on 'Antiplatelet therapy'.)

Uncertain role of systemic antibiotics to prevent ventilator-associated pneumonia (December 2024)

Ventilator-associated pneumonia (VAP) is a significant cause of mortality in patients in the intensive care unit (ICU). In a recent randomized trial of patients with moderate or severe traumatic brain injury (TBI) or acute stroke, ceftriaxone 2 g intravenously (IV) within 12 hours of intubation reduced 7-day VAP rates (14 versus 32 percent) and 28-day mortality rates (15 versus 25 percent) compared with placebo without excess adverse effects [56]. However, in a subsequent meta-analysis including that trial and six others with over 800 patients with acute brain injury (stroke, TBI, or post-cardiac arrest), a short course of peri-intubation IV antibiotics reduced the incidence of VAP, but significant differences in the number of ventilator-free days, ICU length of stay, or in-hospital mortality were not detected [57]. Given the uncertainty around these effects, practice among UpToDate contributors vary; some do not routinely use systemic antibiotics for prevention of VAP in the ICU because of concern for promoting antibiotic resistance, whereas others suggest a single peri-intubation dose of ceftriaxone to prevent VAP in selected populations at high risk (eg, patients with acute TBI). (See "Risk factors and prevention of hospital-acquired and ventilator-associated pneumonia in adults", section on 'Prevention' and "Management of acute moderate and severe traumatic brain injury", section on 'Mechanical ventilation'.)

ADULT PULMONOLOGY

Polygenic risk score to identify undiagnosed COPD (January 2025)

Chronic obstructive pulmonary disease (COPD) remains underdiagnosed despite case-finding strategies to actively identify those who have compatible symptoms and clinical risk factors (eg, smoking) and would thus warrant confirmatory spirometry testing. In a study evaluating almost 7500 patients from two cohorts from the United States, adding a polygenic risk score (PRS) to a traditional case-finding questionnaire helped retrospectively identify additional patients with undiagnosed moderate to severe airflow obstruction, particularly among younger patients with lower COPD risk [58]. This study highlights the potential value of incorporating genetic risk to identify patients for spirometry testing. However, whether patients identified by PRS rather than traditional case-finding benefit from early COPD treatment remains unknown, and PRS is not yet routinely used in clinical practice. (See "Chronic obstructive pulmonary disease: Risk factors and risk reduction", section on 'Gene polymorphisms'.)

Mouth taping and obstructive sleep apnea (January 2025)

Social media has promoted mouth taping as a treatment for obstructive sleep apnea (OSA), but its efficacy is unclear. A recent study of 54 patients with OSA reported an increase in inspiratory flow during drug-induced sleep endoscopy (which simulates sleep) in the closed-mouth position compared with the open-mouth position [59]. However, in 22 percent of patients, mouth closure resulted in velopharyngeal obstruction that reduced inspiratory flow, which could be harmful during sleep. Further studies are needed before mouth taping can be routinely recommended for patients with OSA. (See "Obstructive sleep apnea: Overview of management in adults", section on 'Investigational'.)

Use of anti-inflammatory reliever therapies to reduce asthma exacerbations (November 2024)

Use of inhalers containing both a fast-acting bronchodilator and anti-inflammatory inhaled corticosteroids (ICS) for relief of symptoms has reduced the rate of asthma exacerbations compared with short-acting beta-agonists (SABA) alone in several randomized trials of adolescents and adults. In a new network meta-analysis, compared with SABA alone, severe asthma exacerbations were significantly reduced for both ICS-formoterol (13 trials, 19,184 patients; risk difference 10.3 percent, risk ratio [RR] 0.65) and ICS-SABA (4 trials, 4852 patients; risk difference 4.7 percent, RR 0.84) [60]. Our authors recommend these anti-inflammatory reliever therapies for those with variable asthma symptoms or frequent exacerbations and prefer them for all patients with asthma. (See "Ongoing monitoring and titration of asthma therapies in adolescents and adults", section on 'Anti-inflammatory reliever therapy (AIR) to reduce exacerbations'.)

ADULT RHEUMATOLOGY

Giant cell arteritis in patients initially diagnosed with polymyalgia rheumatica (April 2025)

Polymyalgia rheumatica (PMR) may be an isolated diagnosis or a feature of giant cell arteritis (GCA); however, the frequency with which patients with isolated PMR are eventually diagnosed as having GCA has been unclear. In a prospective cohort study of 62 patients with PMR, 3 percent of patients had radiologic evidence of subclinical GCA and another 3 percent developed late-onset GCA during the following year [61]. Although the risk is relatively low, GCA should be considered in all patients presenting with PMR. At presentation and at each follow-up visit, we assess for symptoms or physical findings referable to GCA (eg, new-onset headache, visual impairment, jaw pain with mastication) and pursue large-vessel imaging as indicated by symptoms. (See "Clinical manifestations and diagnosis of polymyalgia rheumatica", section on 'Association with GCA'.)

Recurrence of acute anterior uveitis (November 2024)

Patients with acute anterior uveitis (AAU) may experience a single episode or evolve to have recurrent disease; however, it is unclear what factors are associated with disease recurrence. In a study that followed over 2000 patients with AAU for a median of 8.9 years, 46 and 27 percent of patients experienced disease recurrence in the ipsilateral or contralateral eyes, respectively [62]. Factors associated with a higher risk of recurrent uveitis included underlying inflammatory arthritis/positive human leukocyte antigen B27 (HLA-B27), Māori ethnicity, and, for ipsilateral recurrence, viral uveitis, Asian ethnicity, and older age. Patients with risk factors for recurrent AAU should be counseled appropriately; future research is required to investigate if they might benefit from more aggressive monitoring and treatment. (See "Uveitis: Treatment", section on 'Prognosis'.)

GYNECOLOGY

Use of extended human papillomavirus genotyping to determine cervical cancer screening follow-up (April 2025)

In April 2025, the Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee published recommendations for using extended human papillomavirus (HPV) genotyping results to guide clinical management of patients undergoing cervical cancer screening [63]. Extended HPV genotyping beyond 16 and 18 identifies two additional risk groups based on the risk of progression to cervical intraepithelial neoplasia [CIN] 3+. One group consists of HPV 45, 33/58, 31, 52, 35/39/68, and 51, and the other consists of HPV 56/59/66. This approach provides additional risk stratification (table 5) and guides appropriate follow-up (table 6). In the United States, only extended HPV genotyping assays approved by the US Food and Drug Administration should be used. (See "Cervical cancer screening: Risk assessment, evaluation, and management after screening", section on 'Terminology and incidence' and "Cervical cancer screening: Risk assessment, evaluation, and management after screening", section on 'HPV positive, genotyping performed'.)

Role of urodynamic testing in evaluating female urinary incontinence (April 2025)

While urodynamic testing has no role in the initial evaluation of females with stress urinary incontinence, studies continue to evaluate its utility in the initial evaluation of females with urgency or mixed urinary incontinence. In a multicenter trial of nearly 1,100 female patients with refractory overactive bladder or urgency-predominant mixed urinary incontinence, 15-month treatment success rates were similar whether the treatment was based on urodynamics with clinical assessment or clinical assessment alone [64]. These findings support our practice of not performing urodynamic testing in the initial evaluation of urinary incontinence in female patients whose symptoms are consistent with stress, urgency, or mixed urinary incontinence. (See "Female urinary incontinence: Evaluation", section on 'Clinical tests, including urodynamic testing'.)

Male partner treatment to prevent recurrence of bacterial vaginosis (March 2025)

Treatment of male sex partners to reduce bacterial vaginosis (BV) recurrence in females is an area of ongoing study. In a trial of 150 male-female monogamous couples with confirmed BV in the female, treatment of the male partner for one week with an oral and topical antibiotic (metronidazole tablet and clindamycin cream) in addition to standard antimicrobial treatment of the female patient reduced recurrences at 12 weeks compared with treating the female patient only (35 versus 63 percent; risk difference -2.6 recurrences per person-year) [65]. Based on these results, we now suggest dual topical and oral antimicrobial male partner therapy as an effective strategy to reduce BV recurrence in female patients. (See "Bacterial vaginosis: Initial treatment", section on 'Males'.)

New copper 175 mm2 intrauterine device (March 2025)

Patients who desire long-acting contraception will have two copper intrauterine devices (IUDs) to consider. The novel copper 175 mm² device (commercial name Miudella) has been approved for three years of use and will be commercially available later in 2025 [66]. Compared with the copper 380 mm² IUD, the new device has less than half the copper, which may reduce uterine cramping and bleeding; the applicator has a smaller diameter and is rounded, which may make placement easier for nulliparous patients or those with cervical stenosis; and the nitinol frame is flexible, which may better adapt to the intrauterine cavity and potentially reduce expulsion risk. (See "Intrauterine contraception: Background and device types", section on 'Device types and characteristics'.)

Human papillomavirus- versus cytology-based cervical cancer screening (January 2025)

Cervical cancer screening can be performed using a human papillomavirus (HPV)- or cytology-based test. While many guidelines have switched to HPV-based testing, others continue to use cytology as the primary screening test. In a recent randomized trial including over 395,000 participants aged 30 to 64 years, HPV-based screening resulted in fewer patients developing cervical cancer compared with cytology-based screening during the eight-year study period (hazard ratio 0.83, 95% CI 0.7-0.98) [67]. These data are consistent with previous evidence that HPV-based testing is superior to cervical cytology and support the increasing utilization of primary HPV testing for cervical cancer screening. (See "Screening for cervical cancer in resource-rich settings", section on 'Relative risks and benefits of each method'.)

Medication abortion in patients with pregnancy of unknown location (December 2024)

Patients seeking abortion who are found to have a pregnancy of unknown location (PUL) are typically managed either expectantly until the location is known or by uterine aspiration. Medication abortion before localization was investigated in a randomized trial of >1500 patients seeking this procedure at ≤6 weeks with a PUL [68]. Patients who received mifepristone plus misoprostol before confirmation of an intrauterine pregnancy (IUP) had a similar rate of complete abortion as those in whom medication was delayed until IUP confirmation. However, in patients who did not achieve a complete abortion, treatment before pregnancy localization resulted in a higher rate of ongoing IUP (3 versus 0.1 percent) and included one ruptured ectopic pregnancy (compared with none with delayed treatment). In our practice, most patients with PUL who are seeking abortion are managed with uterine evacuation. (See "Approach to the patient with pregnancy of unknown location", section on 'Hemodynamically stable patients'.)

Levonorgestrel intrauterine devices and breast cancer risk (November 2024)

Estrogen-progestin contraceptives have been associated with a small increase in risk of breast cancer, whereas the impact of progestin-only intrauterine devices (IUD) has been less clear. In an administrative database study, first-time levonorgestrel (LNG) IUD users (any dose) had a small increase in overall risk of breast cancer compared with matched nonusers of hormonal contraception (hazard ratio 1.4), in line with some prior studies [69]. To provide context and assist patients with assessing their own risk, we inform them that the breast cancer risk conferred by LNG IUDs appears to be modestly increased and similar to that of estrogen-progestin contraceptive pills. (See "Intrauterine contraception: Background and device types", section on 'Risk of cancer'.)

OBSTETRICS

Updated guidance regarding delivery of prenatal care (April 2025)

In the United States, patients with uncomplicated pregnancies traditionally have 12 to 14 prenatal visits before giving birth; however, this schedule can be cumbersome and requires significant resources, without clear evidence of benefit. For this reason, the American College of Obstetricians and Gynecologists recently updated their guidance about delivery of prenatal care [70]. They recommend individualization, which may involve fewer visits and utilizing telemedicine or a group prenatal visit in place of some personal visits. We agree with this approach. (See "Prenatal care: Second and third trimesters", section on 'Frequency and content of prenatal visits'.)

Timing of balloon catheter removal during cervical ripening (April 2025)

Balloon catheters are placed intracervically for 6 or 12 hours to ripen the unfavorable cervix for labor induction. In a meta-analysis of six trials including over 1100 patients, the group assigned to planned removal at 6 hours had a shorter interval from balloon placement to delivery than that assigned to 12 hours (mean difference -3.7 hours) and a modest reduction in cesarean birth (30 versus 36 percent) [71]. Other maternal and neonatal outcomes were similar for both groups. A limitation of the analysis was that it was underpowered to reliably assess some outcomes. We believe planned catheter removal at either 6 or 12 hours is reasonable until more definitive data are available. (See "Induction of labor: Techniques for preinduction cervical ripening", section on 'Single-balloon catheter'.)

Financial incentives for smoking cessation during pregnancy (March 2025)

Smoking during pregnancy is associated with a reduction in birth weight. Financial incentives for pregnant people who smoke reduce smoking rates but their impact on birth weight has not been evaluated. In a meta-analysis of randomized trials including over 2300 pregnant people who smoke, offering financial rewards contingent on smoking cessation resulted in a 46 gram increase in mean birthweight compared with usual care alone (any other support to stop smoking) in intention to treat analysis [72]. This increase in birth weight may make financial incentives a worthwhile investment, particularly if the cost-savings of improved birth outcomes and smoking cessation meet or exceed the cost of the incentive. (See "Tobacco and nicotine use in pregnancy: Cessation strategies and treatment options", section on 'Financial incentives and impact'.)

Prophylactic tranexamic acid did not reduce postpartum hemorrhage after vaginal birth (February 2025)

Tranexamic acid (TXA) is commonly used for managing postpartum hemorrhage (PPH), whereas its role for preventing PPH is unclear. In a meta-analysis of randomized trials, prophylactic use of oxytocin plus TXA after vaginal birth resulted in little or no reductions in PPH ≥500 mL and 1000 mL, blood transfusion, surgical intervention to control hemorrhage, and severe maternal morbidity or death compared with oxytocin plus placebo [73]. The use of additional uterotonics in patients without anemia was modestly reduced. Further investigation is needed to understand whether administering prophylactic TXA in addition to routine oxytocin administration may be beneficial in specific settings. (See "Prophylactic pharmacotherapy to reduce the risk of postpartum hemorrhage", section on 'After vaginal birth'.)

Oral antihyperglycemics are less effective than insulin in pregnancy (February 2025)

Insulin is the preferred antihyperglycemic medication for pharmacotherapy of gestational diabetes mellitus (GDM) because of its well-established safety and efficacy. In a recent randomized trial comparing a sequential strategy of beginning metformin therapy and adding glyburide if glucose targets were not met versus a strategy of insulin alone, the oral antihyperglycemic strategy resulted in higher rates of large-for-gestational-age infants and maternal hypoglycemia [74]. We continue to recommend insulin therapy for management of persistent hyperglycemia in pregnancy. (See "Gestational diabetes mellitus: Glucose management, maternal prognosis, and follow-up", section on 'Choice of pharmacotherapy'.)

Pregnancy in beta thalassemia minor (February 2025)

Beta thalassemia minor is considered an asymptomatic (or minimally symptomatic) carrier state. A new study involving 347 pregnancies in individuals with beta thalassemia minor documented higher rates of anemia and associated risks than expected, including third-trimester anemia in 31 percent, postpartum hemorrhage in 9 percent, and transfusions in 4 percent antepartum and 4.3 percent postpartum [75]. Of concern, 26 individuals were treated with intravenous iron, which was deemed inappropriate in 12, presumably because they were misdiagnosed as having iron deficiency. These data emphasize the importance of considering and accurately classifying the cause of anemia in individuals with beta thalassemia minor. (See "Management of thalassemia", section on 'Pregnancy' and "Anemia in pregnancy", section on 'Causes of anemia'.)

Respiratory syncytial virus vaccination in pregnancy and risk of preterm birth (January 2025)

Respiratory syncytial virus (RSV) infection is a major cause of morbidity and mortality in infants. Maternal vaccination with the inactivated nonadjuvanted recombinant RSV vaccine (RSVPreF; Abrysvo) can reduce this risk. While randomized trials have established the vaccine's safety and efficacy, a trend toward an increased risk of preterm birth was observed. Now, the final analysis of a randomized trial including more than 7000 pregnant individuals worldwide reported that preterm birth rates were similar for those vaccinated with RSVPreF versus placebo (5.7 versus 4.7 percent), with most of the preterm births occurring at ≥34 weeks of gestation [76]. These data are consistent with other studies and further support our practice of vaccinating eligible pregnant individuals with the RSVPreF vaccine. (See "Immunizations during pregnancy", section on 'Strategies for prevention'.)

Prenatal cell-free DNA screening and maternal cancer (January 2025)

Prenatal cell-free (cf) DNA screening for fetal aneuploidy may suggest occult maternal cancer, but data are limited. In a prospective study, cancer was detected in 52 of 107 mothers who had unusual prenatal cfDNA results (eg, copy-number gains and losses across ≥3 chromosomes) and were evaluated by a cancer-screening protocol that included a genome wide platform, whole-body magnetic resonance imaging (MRI), and laboratory tests [77]. Whole-body MRI had sensitivity and specificity of 98 and 88.5 percent, respectively, for detecting occult cancer, whereas physical examination and laboratory tests were of limited value. When prenatal cfDNA screening is offered, patient counseling should include the possibility that the results may be suspicious for maternal cancer. Although the study findings are informative, the best approach for diagnostic evaluation in this setting remains unclear. (See "Prenatal screening for common fetal aneuploidies: Cell-free DNA test", section on 'False-positive cfDNA test results'.)

Neonatal respiratory morbidity at 34 to 36 weeks gestation (December 2024)

Use of antenatal corticosteroids (ACS) at 34 to 36 weeks of gestation to reduce the risk of neonatal morbidity in patients at high risk of preterm birth is controversial. A secondary analysis of a randomized trial recently provided data for counseling patients. The relative risk of respiratory morbidity was nearly two-fold higher in the cesarean birth group compared with the planned vaginal birth group [78]. The absolute risks varied by week of gestation, and the frequency of severe morbidity was modest in both groups by 36 weeks. We do not administer ACS to patients at 34 to 36 weeks in whom preterm vaginal birth is likely. For patients planning a preterm cesarean birth, we use data from this analysis to inform them about the benefits of ACS and data from prior studies about potential long-term harms and make a shared decision. (See "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery", section on '34+0 to 36+5 weeks'.)

Diabetic ketoacidosis in pregnancy and severe maternal morbidity (December 2024)

Diabetic ketoacidosis (DKA) is a serious complication of pregnancy. Among nearly 400,000 pregnancies affected by pre-existing diabetes mellitus in a nationally representative United States database (2010-2020), the prevalence of DKA antepartum and at delivery hospitalization was approximately 3 and 1 percent, respectively [79]. Patients who had DKA during the delivery hospitalization had a much higher risk of nontransfusion severe maternal morbidity compared with patients with diabetes without DKA (21 versus 2 percent). Our approach to managing DKA in pregnancy is shown in the algorithm (algorithm 1). (See "Diabetic ketoacidosis in pregnancy", section on 'Epidemiology' and "Diabetic ketoacidosis in pregnancy", section on 'Outcome'.)

Hidradenitis suppurativa and adverse maternal and neonatal outcomes (November 2024)

Although hidradenitis suppurativa (HS) is a relatively common disorder, studies assessing pregnancy and neonatal outcomes for patients with HS are limited. In a retrospective study of short- and long-term hospitalization data from mothers and neonates from over 1 million hospital births in Canada, maternal HS was associated with increased risk for adverse maternal pregnancy outcomes and pregnancy complications (eg, hypertensive disorders of pregnancy, gestational diabetes, severe maternal morbidity, preterm birth, and congenital anomalies) [80]. Both mothers with HS and their neonates also had an increased long-term risk for rehospitalization. These findings provide further support for a link between HS and adverse pregnancy outcomes and provide new insight into long-term adverse health events in the children of mothers with HS. (See "Hidradenitis suppurativa: Pathogenesis, clinical features, and diagnosis", section on 'Associated disorders and syndromes'.)

Perinatal HIV transmission continues to occur in the United States (November 2024)

In the United States, when pregnant individuals with HIV and their infants receive all applicable perinatal transmission prevention interventions, perinatal HIV transmission rates can be reduced to less than 1 percent. However, cases of perinatal HIV transmission still occur, as outlined by a recently published case series of six children diagnosed with HIV due to perinatal transmission in 2022 [81]. Causes included delayed entry to prenatal care, discovery of HIV diagnosis during pregnancy rather than preconception, and delays in antiretroviral therapy (ART) initiation during pregnancy. Potential opportunities to reduce transmission include increasing pre-exposure prophylaxis (PrEP) utilization, routine HIV testing among individuals of childbearing age who are at high risk of HIV acquisition, and rapid start of ART for pregnant individuals with HIV. Additionally, once a mother is diagnosed with HIV, all biological children should be tested for HIV to avoid delayed identification. (See "Pediatric HIV infection: Epidemiology, clinical manifestations, and outcome", section on 'Resource-rich settings'.)

Risk of chronic hypertension after a hypertensive disorder of pregnancy (November 2024)

Increasing evidence indicates that the occurrence of a hypertensive disorder of pregnancy (HDP; preeclampsia, gestational hypertension) identifies women at high risk of developing chronic hypertension later in life. In a study of all Danish residents giving birth at ≥20 weeks from 1995-2018 except those with prepregnancy cardiovascular disease or chronic hypertension, the cumulative incidence of initiating an antihypertensive medication within two years of delivery was 32 to 44 percent in those with HDP and 1.8 percent in those with normotensive pregnancies [82]. These and previous data support close postpartum blood pressure monitoring followed by at least annual measurement of blood pressure in women with a history of HDP. (See "Treatment of hypertension in pregnant and postpartum patients", section on 'Development of hypertension in nonpregnant patients after hypertension first presenting in pregnancy'.)

Pregnancy in vascular Ehlers-Danlos syndrome (October 2024)

While pregnant persons with vascular Ehlers-Danlos syndrome (vEDS) have an increased risk of maternal morbidity and mortality, more information is needed on this rare disorder to appropriately counsel and manage patients. In a systematic review including six studies with a total of 412 pregnancies, the maternal mortality rate was 5.7 percent (22 of 386 patients); deaths were attributed to vascular rupture or dissection (12 patients), uterine rupture (7 patients), and rupture of other organs (1 patient) [83]. There were no deaths in the group of 28 patients who underwent a scheduled cesarean delivery. Providers should carefully counsel patients with vEDS about the risks associated with pregnancy and consider scheduling cesarean delivery at 37 weeks of gestation. (See "Ehlers-Danlos syndromes: Overview of the management", section on 'Pregnancy, delivery, and postpartum care'.)

PEDIATRICS: GENERAL PEDIATRICS

Reduction of radial head subluxation ("pulled elbow") in children (March 2025)

Radial head subluxation (RHS) commonly occurs in young children (<5 years old) when a parent or caregiver grabs the arm to prevent falling or pulling away (figure 3); the best method for reduction of an RHS is debated. In a meta-analysis of 11 randomized trials (almost 1200 children with RHS undergoing reduction), the pooled first-attempt success rate was higher following the use of the hyperpronation method (figure 4) compared with the supination/flexion method (figure 5) (91 versus 75 percent, respectively) [84]. Limitations of this analysis include the high risk of bias in most of the included studies and interstudy differences in the definition of a successful reduction. These findings support our suggestion for the hyperpronation method rather than the supination/flexion method to reduce an RHS; however, the supination/flexion method is a reasonable alternative if the clinician is more familiar and skilled with this technique. (See "Radial head subluxation (pulled elbow): Evaluation and management", section on 'Radial head subluxation reduction'.)

Fractures and child abuse in young children (March 2025)

The American Academy of Pediatrics has published a clinical report that provides guidance for the evaluation of fractures in young children [85]. This report reaffirms the importance of a careful history and physical examination with special attention to the reported mechanism of injury, the developmental capability of the child, associated injuries on examination, and the specific type of fracture. A skeletal survey (table 7), under the guidance of a pediatric radiologist or a multidisciplinary child abuse team led by a child abuse specialist, is indicated for children <24 months old who have a fracture that is concerning for abuse (table 8). (See "Orthopedic aspects of child abuse", section on 'Overview' and "Physical child abuse: Recognition", section on 'Fractures'.)

Pediatric deaths due to influenza-associated encephalopathy or encephalitis (March 2025)

Influenza-associated encephalopathy or encephalitis (IAE) is a rare complication of influenza that can be fatal. New surveillance data from the Centers for Disease Control and Prevention indicate that IAE accounts for a significant proportion of pediatric influenza-associated deaths [11]. Of nearly 1800 influenza-associated pediatric deaths occurring between the 2010-2011 season and the 2023-2024 season, 157 (9 percent) were caused by IAE. Additionally, of the 68 influenza-associated pediatric deaths reported from October 1, 2024 through February 8, 2025, 9 (13 percent) were due to IAE. It is not yet clear whether this represents a higher incidence of IAE this season; however, IAE should be considered in children with influenza and abnormal neurologic findings. (See "Seasonal influenza in children: Clinical features and diagnosis", section on 'Central nervous system'.)

Consensus guideline on melatonin for sleep in typically developing children (March 2025)

An international group of pediatric sleep experts has published a new consensus guideline on the use of melatonin for sleep in typically developing children [86]. The panel recommends performing a thorough clinical evaluation to rule out other causes of chronic insomnia before considering melatonin, using behavioral approaches before and along with melatonin, limiting duration to as short of a time period as possible and no longer than three to six months in most cases, and storing melatonin safely in locked containers out of the reach of children. The guideline provides typical dose ranges of melatonin by age, up to a maximum of 5 mg nightly in adolescents. Our approach is consistent with these guidelines. (See "Pharmacotherapy for insomnia in children and adolescents: A rational approach", section on 'Melatonin'.)

Suicide in preteens (February 2025)

Although suicide deaths in preteens are rare, they remain a leading cause of death and the incidence appears to be increasing over time. A recent study in children ages 8 to 12 years found that the rate of suicide between the periods 2009 to 2015 and 2016 to 2023 increased by 40 percent [87]. Among preteens with risk factors for suicide, such as psychiatric disorders, we suggest monitoring for suicidal ideation and behavior. Patients with suicidality should be treated for any underlying disorder and provided with a safety plan. (See "Suicidal behavior in children and adolescents: Epidemiology and risk factors", section on 'Age'.)

Nonoperative management of appendicitis in children (January 2025)

For children with early appendicitis, the role of nonoperative management with antibiotics (NOM) has been debated. In a multicenter trial of 846 children with appendicitis, 34 percent of children assigned to NOM required an appendectomy within one year. Approximately one-half of these patients required appendectomy at the index admission, of whom 35 percent had perforated appendicitis [88]. For children assigned to prompt appendectomy, 7 percent had normal pathology and 6 percent had perforation. Based on this first randomized trial of NOM in children with early appendicitis, we continue to perform appendectomy for most of these patients. However, NOM may be an option for selected children after shared decision-making (algorithm 2). (See "Acute appendicitis in children: Management", section on 'Nonoperative management'.)

Early sugar intake and long-term health outcomes (January 2025)

In a new study that analyzed the effects of sugar rationing in the United Kingdom after World War II, reduced sugar consumption to levels within current dietary guidelines, from in utero exposure up to two years of age, was associated with a decreased risk of type 2 diabetes, hypertension, and obesity in adulthood by 20 to 35 percent [89]. Approximately two-thirds of the risk reduction was attributable to sugar restriction between six months and two years of age. These findings expand the evidence of "metabolic programming" and demonstrate that limiting sugar exposure during the first two years of life has important long-term health benefits. (See "Definition, epidemiology, and etiology of obesity in children and adolescents", section on 'Infancy and early childhood'.)

Atherosclerotic cardiovascular disease (ASCVD) risk factors in adolescence and ASCVD events in adulthood (January 2025)

A growing body of evidence suggests that vascular changes predisposing to adult atherosclerotic cardiovascular disease (ASCVD) begin in childhood. In a recent study using data from seven different longitudinal studies including over 11,000 participants who were followed from adolescence to a mean age of 50 years, the presence of ASCVD risk factors in adolescence (eg, hypertension, obesity, smoking, or hypercholesterolemia) was independently associated with experiencing fatal and nonfatal ASCVD events in adulthood [90]. The risk increased with increasing number of risk factors. These findings highlight the importance of screening for ASCVD risk factors during childhood and adolescence and intervening at a young age. (See "Overview of pediatric risk factors for premature atherosclerotic cardiovascular disease (ASCVD)", section on 'Evidence linking childhood risk factors to ASCVD events in adulthood'.)

2025 immunization schedule for infants, children, and adolescents published by the CDC (December 2024)

The United States Centers for Disease Control and Prevention has provided the 2025 updates for the routine immunization schedules for infants, children, and adolescents ≤18 years of age [15]. Notable changes in the 2025 schedules include an additional dose of COVID-19 vaccine for moderately or severely immunocompromised individuals and the addition of Vaxelis to PedvaxHIB as a preferred Hib vaccine for American Indian and Alaska Native infants. (See "Standard immunizations for children and adolescents: Overview", section on 'Routine schedule'.)

Screening for anxiety and depression in children and adolescents with epilepsy (November 2024)

New consensus-based recommendations on the diagnosis and treatment of anxiety and depression in children and adolescents with epilepsy are available from the International League Against Epilepsy (ILAE) [91]. These recommendations include screening for anxiety and depression in all children and adolescents with epilepsy at age 7 years and annually thereafter, use of a formal screening questionnaire to assess symptoms of anxiety and depression, and closer surveillance for groups at higher risk (eg, those with suicidal behavior). Screening interviews should include the child with epilepsy and their parents or other caregivers, and they should be informed about the potential adverse behavioral effects of antiseizure medications. We agree with the ILAE recommendations, including referral of patients with moderate to severe depression or anxiety to a mental health care clinician. (See "Epilepsy in children and adolescents: Comorbidities, complications, and outcomes", section on 'Anxiety and depression'.)

PEDIATRIC NEONATOLOGY

Universal screening for congenital cytomegalovirus infection (March 2025)

Newborn screening for congenital cytomegalovirus (cCMV) has been proposed by public health experts, but the most reliable and cost-effective method is uncertain. Two recent studies reported on the experience of performing universal cCMV screening with dried blood spots [92,93]. Combined, these studies screened >600,000 newborns, and 863 (0.14 percent) screened positive. The false-positive rate was 4 percent. Among confirmed cases, >80 percent were asymptomatic whereas 12 to 16 percent had either isolated hearing loss or findings consistent with symptomatic cCMV disease. These reports suggest that universal screening is feasible; however, important challenges and uncertainties remain (eg, ensuring timely follow-up and linkage to care after a positive screen, and lack of standardized criteria for initiating antiviral treatment). (See "Congenital cytomegalovirus (cCMV) infection: Clinical features and diagnosis", section on 'Universal newborn screening'.)

Updated guidance on newborn pulse oximetry screening (January 2025)

The American Academy of Pediatrics (AAP) has released updated guidance on newborn pulse oximetry screening (POS) for critical congenital heart disease [94]. Key changes from the 2011 guidelines include endorsement of a simplified screening algorithm that requires only one repeated screen if the initial screen is equivocal (algorithm 3), and clarification that screening must be performed in room air. For newborns receiving oxygen therapy, pulse oximetry monitoring should be performed as clinically indicated for their condition, and the screening procedure should be deferred until the infant has been weaned off oxygen. We agree with the approach recommended by the AAP. (See "Newborn screening for critical congenital heart disease using pulse oximetry", section on 'Screening algorithm'.)