What's new in primary care

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.

SCREENING

Screening and surveillance of individuals at increased risk for gastric cancer in the United States (June 2025)

Universal screening programs for gastric cancer (GC) exist in several countries with a high incidence of gastric cancer. Although the incidence of gastric cancer in the United States is low, some population subgroups are at elevated risk of gastric cancer but do not routinely receive GC screening. In its recent clinical practice update, the American Gastroenterological Association (AGA) recommends GC screening and surveillance with upper endoscopy in these individuals [1]. This includes those who are first-generation immigrants from regions with a high incidence of GC or have a family history of GC in a first-degree relative without a known hereditary cancer syndrome. We also suggest screening in these patients, but because the effect on cancer-related mortality is uncertain, we individualize screening decisions after discussing the potential benefits and harms with each patient. (See "Gastric cancer screening", section on 'Approach and rationale for 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 testing (FIT) versus colonoscopy (0.24 versus 0.22 percent at 10 years) [2]. Participation in any form of CRC screening was higher in the group assigned to FIT (40 versus 32 percent). For adults at average risk of CRC, colonoscopy every 10 years or annual FIT are our preferred screening strategies. (See "Screening for colorectal cancer: Strategies in patients at average risk", section on 'Test selection'.)

IMMUNIZATIONS

New pentavalent meningococcal vaccine (June 2025)

Penmenvy is a new pentavalent meningococcal vaccine that includes the five serotypes A, B, C, W, and Y by combining MenACWY-CRM (Menveo) with MenB-4C (Bexsero). In 2025, the US Food and Drug Administration approved Penmenvy for individuals aged 10 through 25 years who warrant both MenACWY and MenB at the same visit [3]. In contrast, the existing pentavalent vaccine, Penbraya, combines MenACWY-TT (sold as Nimenrix outside of the United States) and MenB-FHbp (Trumenba). Because MenB vaccine formulations are not interchangeable, individuals who receive Penmenvy will need to complete a MenB series with MenB-4C. The ACIP has voted to incorporate this formulation into existing recommendations on meningococcal vaccination, although formal policy approval is pending [4]. (See "Meningococcal vaccination in children and adults", section on 'Pentavalent vaccines (ACWY and B serogroups)'.)

COVID-19 vaccine recommendations in the United States (June 2025)

Recommendations on COVID-19 vaccination from the Centers for Disease Control and Prevention (CDC) are evolving. As of the end of May 2025, the CDC immunization schedule included vaccination for all adults ≥18 years and for children 6 months to 17 years with a moderately to severely immunocompromising condition; for immunocompetent children, it advised shared decision making on vaccination [5]. Although the risk of severe disease has decreased substantially since the start of the pandemic, COVID-19 remains an important cause of hospitalization and death; from 2023 to 2024, rates of COVID-19-associated hospitalization were similar to or higher than influenza-associated hospitalization for children ≤4 years and for adults ≥18 years [6]. We recommend COVID-19 vaccination for individuals ≥6 months who are at high risk for severe outcomes, which includes older adults (≥65 years) and those who are immunocompromised, pregnant, or have underlying medical comorbidities as outlined in the table (table 1). For people at lower risk (eg, healthy children and younger adults), we individualize the decision to vaccinate; although their risk of severe outcomes with COVID-19 is lower, some risk remains, and vaccination is an appropriate option for those who prioritize minimizing that risk. (See "COVID-19: Vaccines", section on 'Indications and vaccine selection'.)

Impact of herpes zoster vaccination on dementia risk (May 2025)

A number of observational studies have suggested that herpes zoster vaccination may reduce the risk of dementia. Further evidence of a protective effect from the vaccine comes from two large database studies in Wales and Australia, which estimated that eligibility for the herpes zoster vaccine program reduced the absolute incidence of a dementia diagnosis by 1 to 2 percent over approximately seven years of follow-up [7,8]. Further data are needed to confirm the benefit in terms of dementia risk, but we continue to encourage age-appropriate herpes zoster vaccination to prevent herpes zoster and postherpetic neuralgia. (See "Prevention of dementia", section on 'Herpes zoster vaccination'.)

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) [9]. 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 2), 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 [10]. 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 [11]. 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 3). (See "Respiratory syncytial virus infection in adults", section on 'Risk of Guillain Barré'.)

GENERAL INTERNAL MEDICINE

Premedication of patients with a history of iodinated contrast hypersensitivity reaction (May 2025)

Modern low-osmolality iodinated contrast media carry a small risk of immediate ("allergic-like") hypersensitivity reactions, but the benefit of premedicating patients with any severity of past reaction is unclear. A new multidisciplinary consensus guideline no longer recommends premedicating patients with a history of mild allergic-like reactions since any benefit is small, whereas adverse reactions from glucocorticoids and antihistamines can occur [12]. The guideline recommends changing contrast agents in all patients with a history of past reaction, when feasible, since data support the favorable impact of this practice. We generally agree with these recommendations, and continue to administer premedication in those with a history of moderate or severe allergic-like reactions. (See "Patient evaluation prior to oral or iodinated intravenous contrast for computed tomography", section on 'Preventing recurrent allergic-like reactions'.)

Military sexual trauma is associated with suicide attempts (May 2025)

Military sexual trauma (MST) is likely to have adverse consequences for veterans, but documentation of such outcomes is limited. In a longitudinal cohort study of over five million older United States veterans, those with a history of MST had a higher cumulative incidence of suicide attempts at age 90 compared with those without MST (18.7 versus 6.3 percent for men; 8.7 versus 2.9 percent for women) [13]. MST should be considered in veterans with symptoms of posttraumatic stress disorder, anxiety, depression, sleep difficulties, or disordered eating. (See "Medical care of the military veteran", section on 'Sexual trauma'.)

Digital screen use and myopia risk (May 2025)

Studies suggest that near-vision activities (eg, reading at close range, digital screen use) increase risk for the development of myopia in children and adults, though the strength of this association is uncertain. In a meta-analysis of 34 observational studies from multiple countries including over 314,000 children and adults (mean age 9 years), myopia risk increased nonlinearly with duration of digital screen use (ie, smartphones, tablets, game consoles, computers, television) [14]. Odds of myopia ranged from 5 percent higher with one hour of daily exposure to 97 percent higher with four hours. These data suggest that limiting digital screen use could be a useful strategy to prevent or slow the progression of myopia. (See "Refractive errors in children", section on 'Natural history and risk factors' and "Visual impairment in adults: Refractive disorders and presbyopia", section on 'Risk factors'.)

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 [15]. 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 [16]. 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'.)

Reduced-dose apixaban and rivaroxaban for indefinite venous thromboembolism treatment (April 2025)

The optimal anticoagulant dose for prevention of venous thromboembolism (VTE) among patients at high risk of recurrence is unknown. In a trial of over 2700 such patients who had completed 6 to 24 months of anticoagulation, patients who transitioned either to reduced-dose apixaban (2.5 mg twice daily) or rivaroxaban (10 mg once daily) had a higher five-year VTE recurrence rate, compared with patients who continued to take full-dose anticoagulants (2.2 versus 1.8 percent) [17]. However, low-dose anticoagulant therapy was associated with a lower risk of major and/or clinically relevant bleeding (9.9 versus 15.2 percent). Low-dose apixaban or rivaroxaban is appropriate for most patients at high risk of recurrent VTE who require indefinite anticoagulation. (See "Selecting adult patients with lower extremity deep venous thrombosis and pulmonary embolism for indefinite anticoagulation", section on 'Reduced-dose regimens for indefinite anticoagulation'.)

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 [18]. 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 [19]. 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".)

Suzetrigine, a first-in-class nonopioid analgesic, now available for acute pain (March 2025)

Suzetrigine, a first-in-class nonopioid oral analgesic, has been approved by the US Food and Drug Administration for management of acute pain in adults and is now available. Suzetrigine is a selective inhibitor of the Na_v 1.8 voltage-gated sodium channel, which is expressed in the dorsal root ganglia and is involved in transmission of nociceptive signals to the spinal cord. In randomized trials of 303 patients who had acute pain after abdominoplasty and 274 patients after bunionectomy, suzetrigine (100 mg orally followed by 50 mg orally every 12 hours) reduced pain scores compared with hydrocodone/acetaminophen (5 mg/325 mg orally every six hours) or placebo [20]. Further study is required to determine the role of suzetrigine in acute pain management. (See "Nonopioid pharmacotherapy for acute pain in adults", section on 'Suzetrigine, a novel Nav1.8 inhibitor'.)

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 [21]. 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'.)

PRIMARY CARE ALLERGY AND IMMUNOLOGY

Withdrawal pruritus with cetirizine and levocetirizine (May 2025)

Cetirizine and levocetirizine are effective nonsedating antihistamines that are commonly recommended for urticaria, seasonal allergies, and various pruritic conditions. However, the US Food and Drug Administration (FDA) issued a safety communication that rare patients may experience increased itching that is sometimes disabling when reducing or discontinuing these medications, particularly after three or more months of regular administration [22]. Restarting the medication and slowly tapering down the dose may help in some cases, and the problem is generally self-limited. (See "Chronic spontaneous urticaria: Standard management and patient education", section on 'Withdrawal pruritus with cetirizine and levocetirizine'.)

PRIMARY CARE CARDIOVASCULAR MEDICINE

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 [23]. 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'.)

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 [24]. 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'.)

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 [25]. 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 [26]. 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'.)

PRIMARY CARE DERMATOLOGY

Roflumilast foam for chronic plaque psoriasis (June 2025)

Although chronic plaque psoriasis on the scalp can be challenging to treat with traditional topical agents, trials are evaluating new topical strategies. In a randomized trial of 432 adolescents and adults with chronic plaque psoriasis, patients treated with roflumilast 0.3% foam (a topical phosphodiesterase 4 inhibitor) had greater improvement in scalp and body psoriasis compared with patients in the vehicle group [27]. Roflumilast foam also improved pruritus and was generally well tolerated. The findings contributed to the US Food and Drug Administration approval of roflumilast 0.3% foam for psoriasis on the scalp and body in adults and children ages 12 years and older [28]. Roflumilast foam may help to simplify treatment for patients with both scalp and body psoriasis. (See "Chronic plaque psoriasis in adults: Treatment of disease amenable to topical therapy", section on 'Topical roflumilast'.)

PRIMARY CARE ENDOCRINOLOGY AND DIABETES

Subclinical hyperthyroidism treatment and risk of atrial fibrillation (June 2025)

There are few data to guide the identification of patients with endogenous subclinical hyperthyroidism for treatment. Endogenous subclinical hyperthyroidism (subnormal thyroid-stimulating hormone [TSH] with normal thyroxine and triiodothyronine) is unrelated to thyroid hormone therapy and may eventually resolve on its own. In a retrospective cohort study of patients with persistent subclinical hyperthyroidism followed for 4.3 years, the incidence of atrial fibrillation was lower in the patients who were treated (1.6 percent) compared with those not treated or treated <30 days prior to onset of atrial fibrillation (7.4 percent) [29]. These findings support our suggestion to treat individuals at high risk for cardiac complications (eg, older age, presence of cardiovascular disease or its risk factors), particularly if the TSH is <0.1 mU/L (algorithm 1). (See "Subclinical hyperthyroidism in nonpregnant adults", section on 'Patients at high risk for complications'.)

Oral semaglutide and cardiovascular events in adults with type 2 diabetes (June 2025)

In adults with type 2 diabetes, subcutaneous semaglutide improves cardiovascular outcomes, but whether oral semaglutide has a similar benefit was uncertain. In a trial in 9650 patients with type 2 diabetes and atherosclerotic cardiovascular disease and/or chronic kidney disease, oral semaglutide reduced major adverse cardiovascular events (a composite of nonfatal stroke, nonfatal myocardial infarction, and death from cardiovascular causes) compared with placebo over a median follow-up of 50 months [30]. The absolute risk reduction was approximately two percent. Among the individual components of the composite outcome, only the rate of nonfatal myocardial infarction was significantly lower in the oral semaglutide group. Overall, these results suggest that oral and subcutaneous semaglutide have similar cardiovascular benefits, and the oral formulation is a reasonable alternative for injection-averse patients with high cardiovascular risk. (See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects'.)

Switching GLP-1-based therapy in adults with type 2 diabetes (May 2025)

In adults with type 2 diabetes and glycemia above target despite glucagon-like peptide 1 (GLP-1)-based therapy, optimal management is uncertain. In a 40-week trial in 282 adults with type 2 diabetes who were not meeting glycemic goals with dulaglutide 0.75 or 1.5 mg weekly (with or without oral glucose-lowering medications), patients were randomly assigned to tirzepatide (15 mg weekly or maximum tolerated dose) or dose escalation of dulaglutide (to 4.5 mg weekly or maximum tolerated dose) [31]. At 40 weeks of treatment, participants who switched to tirzepatide had greater reduction in glycated hemoglobin (A1C; estimated treatment difference -0.77 percentage points) and body weight (estimated treatment difference -6.9 kg). These findings support the utility of switching to a more potent GLP-1-based agent if additional glucose- or body weight-lowering is required to reach treatment goals. (See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Glycemic efficacy'.)

Global rates of overweight and obesity (March 2025)

Despite numerous associated health risks, rates of overweight and obesity continue to increase worldwide. In a new global analysis, the number of adults with overweight or obesity is expected to increase from 2.1 billion in 2021 to 3.8 billion in 2050, which represents nearly 60 percent of the predicted adult population [32]. Among children and young adults, the projected global prevalence of obesity by 2050 is 15.6 percent for those ages 5 to 14 years, and 14.2 percent for those 15 to 24 years [33]. We continue to promote screening and prevention for all patients, routine growth monitoring and counseling on healthy behaviors and lifestyle for all children, comprehensive lifestyle intervention for children and adults with overweight and obesity, and intensive lifestyle, pharmacologic, or surgical management for those at the highest risk of obesity-related morbidity and mortality. (See "Obesity in adults: Prevalence, screening, and evaluation", section on 'Global'.)

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'.)

PRIMARY CARE GASTROENTEROLOGY

Updated guidelines on eosinophilic esophagitis (January 2025)

The American College of Gastroenterology has published updated guidelines on diagnosis and management of eosinophilic esophagitis (EoE) [39]. The guidelines establish the diagnosis of EoE based esophageal symptoms, ≥15 eosinophils per high-power field on biopsy, and excluding other causes of eosinophilia. Endoscopic evaluation includes obtaining multiple biopsies from two esophageal levels (ie, proximal/mid and distal esophagus). For initial treatment, the guidelines endorse a limited empiric food elimination diet or pharmacologic (proton pump inhibitor or topical glucocorticoid) therapy. Our approach is generally consistent with these guidelines. (See "Treatment of eosinophilic esophagitis (EoE)", section on 'Introduction'.)

PRIMARY CARE GERIATRICS

Risk of delayed bleeding in older adults following head trauma (January 2025)

Older adults, particularly those taking anticoagulant medication, are at high risk for intracranial hemorrhage (ICH) following blunt head trauma. However, the risk of delayed ICH is less well studied. In a prospective observational study of 3425 older adult patients with acute head injury (median age 82, 33 percent of whom were prescribed anticoagulants), acute ICH was identified in 6.7 percent of patients but only 0.4 percent had delayed ICH [40]. The rates of delayed bleeding were similar for patients prescribed anticoagulants versus those who were not. All delayed bleeding occurred between several hours and five days following injury. These findings are consistent with prior studies and support the safety of discharge in older adults with isolated closed head injury who have a normal initial neurologic examination, no bleeding on CT scan (if obtained), and remain stable with no change in neurologic status after 12 hours of observation. (See "Geriatric trauma: Initial evaluation and management", section on 'Risk of bleeding'.)

PRIMARY CARE GYNECOLOGY

Treatment of persistent mixed urinary incontinence in women (June 2025)

The treatment of female patients with mixed urinary incontinence (MUI; ie, symptoms of both stress and urgency urinary incontinence) includes lifestyle modifications, medication, and procedures for persistent symptoms; however, data to guide procedure selection are lacking. In a randomized trial of 137 patients with persistent, moderate-to-severe MUI, both mid-urethral sling surgery and intradetrusor injections of onabotulinumtoxinA resulted in similar improvement in MUI symptoms at six months [41]. These results further support our approach to the treatment of persistent MUI, including the selection of a procedure based on patient preference and predominant symptom. (See "Female urinary incontinence: Treatment", section on 'Mixed urinary incontinence (MUI) treatment'.)

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 [42]. 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 4) and guides appropriate follow-up (table 5). 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'.)

Gepotidacin for acute simple cystitis (April 2025)

In 2025, the US Food and Drug Administration approved gepotidacin, a novel antibiotic that retains activity against organisms resistant to fluoroquinolones and other antibiotic classes, for treatment of acute simple cystitis (uncomplicated urinary tract infection [UTI]) in adult females. In trials, gepotidacin resulted in combined clinical and microbiologic cure rates that were either similar to (51 versus 47 percent) or higher than (59 versus 43 percent) those with nitrofurantoin [43]. Diarrhea was common. Because of antimicrobial stewardship concerns, we reserve this agent for directed therapy of gram-negative pathogens that are resistant to other drug classes; it is not indicated for complicated UTI (including pyelonephritis). (See "Acute simple cystitis in female adults", section on 'Directed antimicrobial selection'.)

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 [44]. 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) [45]. 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 [46]. 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) [47]. 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 "Cervical cancer screening: Benefits, harms, screening methods, and patient risk groups", section on 'Relative risks and benefits of each method'.)

PRIMARY CARE HEMATOLOGY AND ONCOLOGY

Supplemental breast cancer screening strategies (June 2025)

Trials are investigating supplemental breast cancer screening strategies for patients with dense breasts, given limitations with standard mammography. In a randomized trial enrolling 9361 female patients with dense breasts and negative mammograms, the cancer detection rates per 1000 examinations were 17.4 for abbreviated magnetic resonance imaging (MRI), 19.2 for contrast-enhanced mammography, and 4.2 for automated breast ultrasound [48]. Indirect comparisons with an observational cohort suggested higher cancer detection rates compared with digital mammography for all three supplemental screening arms, with the greatest difference for abbreviated MRI. However, recall rates were also higher with supplemental screening. The trial did not measure breast cancer-specific mortality reduction or longer-term harms, such as overdiagnosis. Although we do not consider dense breasts alone to be an indication for MRI screening, in patients undergoing MRI screening for other indications, an abbreviated MRI protocol is an appropriate option. (See "Breast density and screening for breast cancer", section on 'Abbreviated first post-contrast acquisition subtracted (FAST) MRI'.)

Hypophosphatemia with intravenous ferric carboxymaltose (April 2025)

Several intravenous iron formulations are available, with similar efficacy and mostly similar adverse effects profiles. However, recent reports have emphasized a high rate of hypophosphatemia with ferric carboxymaltose (FCM). A new systematic review reported high rates of hypophosphatemia with FCM in randomized trials (50 to 92 percent, versus 2 to 8 percent with other intravenous iron formulations) [49]. This supports our practice of monitoring serum phosphate in all patients receiving more than one dose of FCM, especially individuals with borderline phosphate levels at baseline or receiving repeated doses. (See "Treatment of iron deficiency and iron deficiency anemia in adults", section on 'Hypophosphatemia and cardiac iron uptake'.)

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) [50]. 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'.)

High rate of iron deficiency in athletes (January 2025)

High-intensity athletics can cause iron deficiency by several mechanisms including reduced iron intake, gastrointestinal blood loss, iron loss in sweat, and traumatic hemolysis. A new meta-analysis including over 17,000 college athletes and military recruits reported iron deficiency in 31 percent, using a ferritin cutoff of 30 ng/mL [51]. Female athletes are more likely than male athletes to have iron deficiency; younger and older athletes are equally affected. These observations confirm that high-intensity athletics is a significant risk factor for iron deficiency and support a role for screening in this population. (See "Diagnosis of iron deficiency and iron deficiency anemia in adults", section on 'Epidemiology'.)

PRIMARY CARE INFECTIOUS DISEASES

Respiratory syncytial virus vaccination in older solid organ transplant recipients (June 2025)

Respiratory syncytial virus (RSV) infection is a major cause of morbidity and mortality in transplant recipients, but there are limited data on the safety and efficacy of RSV vaccination in transplant recipients. In an electronic medical record-based case-control study that included over 1500 solid organ transplant recipients aged ≥60 years, vaccine efficacy in this subgroup was 56 percent against RSV-associated hospitalization and 73 percent against symptomatic RSV infection [52]. Vaccine safety was not assessed separately for solid organ transplant recipients; however in general, the vaccine appeared to be safe with a very small excess risk of Guillain-Barre syndrome with the RSVPreF vaccine formulation. We continue to suggest RSV vaccination in solid organ transplant recipients above the age of 60 years. (See "Immunizations in solid organ transplant candidates and recipients", section on 'Respiratory syncytial virus (RSV)'.)

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 [53]. 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'.)

Updated guidelines for treatment of tuberculosis (February 2025)

New guidelines for treating tuberculosis (TB) have been issued by the American Thoracic Society, US Centers for Disease Control, European Respiratory Society, and Infectious Disease Society of America [54]. For drug-susceptible TB in patients ≥12 years of age who meet all conditions, the guidelines conditionally recommend a rifapentine-moxifloxacin-based regimen (rifapentine, moxifloxacin, isoniazid, and pyrazinamide for four months); we suggest a traditional regimen given the need for special monitoring in some patients on the shortened regimen. For patients age 3 months to 16 years with nonsevere, smear-negative, presumed drug-susceptible disease, we agree with the guidelines, which favor a shortened four-month regimen (isoniazid, rifampin, and pyrazinamide, with or without ethambutol). For patients ≥14 years of age with rifampin-resistant TB, we agree with the new guidelines, which favor bedaquiline, pretomanid, and linezolid, with or without moxifloxacin for six months (BPaL[M]). (See "Tuberculosis disease in children: Treatment and prevention", section on 'Regimen selection'.)

PRIMARY CARE NEPHROLOGY AND HYPERTENSION

Bedtime versus morning antihypertensive dosing in frail older adults (June 2025)

Although some trials suggest that bedtime rather than morning dosing of antihypertensive therapy has cardiovascular benefits, the two largest trials found no difference, and we recommend taking antihypertensive drugs at a time of day that optimizes adherence for each individual patient. A new trial compared bedtime versus morning antihypertensive drug dosing in nearly 800 frail, older adults; there were no important differences in all-cause mortality, cardiovascular events, falls, or cognitive decline between the groups [55]. We continue to advise that the timing of antihypertensive therapy be individualized for convenience and maximal adherence. (See "Hypertension in adults: Initial drug therapy", section on 'Approaches with limited evidence of benefit'.)

Intensive blood pressure lowering among those with isolated systolic hypertension and low diastolic pressures (June 2025)

Management of blood pressure (BP) in older adults with isolated systolic hypertension is somewhat controversial because, although intensive systolic BP lowering is beneficial in this age group, there is concern that a low attained diastolic BP as a result of treatment can have adverse cardiovascular consequences. In a meta-analysis of five large goal BP trials composed of nearly 17,000 patients, more intensive as compared with less intensive BP lowering reduced the risk of cardiovascular events and all-cause mortality, irrespective of baseline diastolic BP [56], including among those in the lowest quartile of baseline diastolic BP (mean 65 mmHg). When treating older patients with isolated systolic hypertension, we generally target the optimal systolic BP independent of the diastolic BP, provided the patient does not develop symptoms related to BP lowering. (See "Goal blood pressure in adults with hypertension", section on 'Older adults with isolated systolic hypertension'.)

Nonsteroidal antiinflammatory drugs for pain control in patients with acute renal colic (May 2025)

Kidney stones often present with acute and intense abdominal and/or flank pain (ie, renal colic); we suggest nonsteroidal antiinflammatory drugs (NSAIDs) as the initial choice for pain control in most patients presenting with acute renal colic. A recent Cochrane systematic review of 29 randomized trials (nearly 3600 patients) found that NSAIDs are more effective than placebo in reducing pain (defined as the change in VAS-10 cm pain scores from baseline to 30 minutes after intervention; mean difference -3.84 cm, 95% CI -6.41 to -1.27) [57]. Patients receiving NSAIDs were also less likely to require rescue pain medication than those receiving placebo. These findings provide additional support for the use of NSAIDs as initial pain control in patients with acute renal colic. (See "Kidney stones in adults: Diagnosis and acute management of suspected nephrolithiasis", section on 'Pain control'.)

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 [58]. 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) [59]. 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'.)

PRIMARY CARE NEUROLOGY

Benefits of carpal tunnel surgery in patients with prolonged symptoms (July 2025)

Patients with prolonged carpal tunnel syndrome (CTS) symptoms that persist despite nonsurgical treatments often undergo surgery, but the benefits in this setting are uncertain. In an open-label randomized trial of 934 patients with CTS for a median of eight months, symptom recovery was modestly more frequent in those assigned to surgery than initial glucocorticoid injection by 18-month follow-up (61 versus 45 percent) [60]. However, nearly half of those assigned to initial injection subsequently underwent surgery within the study period. Recovery rates were low for those assigned to injection who underwent no additional treatment or further injections alone (13 and 3 percent, respectively). These results support our preference for surgical intervention for patients with prolonged CTS symptoms. (See "Carpal tunnel syndrome: Treatment and prognosis", section on 'Patient selection'.)

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 [61]. 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) [62]. 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'.)

PRIMARY CARE ORTHOPEDICS AND SPORTS MEDICINE

Exercise to prevent sarcopenia in older adults (May 2025)

Strength training has been studied as a method for preventing sarcopenia in older adults. In the randomized multicenter European DO-HEALTH trial, 1495 community-dwelling adults over 70 were assigned to an exercise intervention that consisted of five simple exercises using only bodyweight or light resistance with no planned increases in load or normal activities three times weekly [63,64]. This intervention had no impact on sarcopenia over three years. These data confirm prior studies that document the ineffectiveness of strength programs that do not emphasize robust exercises with progressive increases in load. (See "Practical guidelines for implementing a strength training program for adults", section on 'General principles'.)

Benefits of the weekend warrior exercise strategy (April 2025)

Evidence is growing that exercising for the same total period over two days ("weekend warriors") versus multiple days provides equivalent overall health benefits. According to a data registry study from over 95,000 participants in the United Kingdom, all-cause mortality rates were similarly lower for individuals who exercised multiple days of the week and "weekend warriors" compared with the higher rates found among inactive individuals [65]. Activity levels were determined by accelerometer-derived data. Although the weekend warrior approach is a reasonable exercise strategy for some, it may increase the risk for overuse injury, while those with comorbidities such as diabetes or hypertension may reap greater disease-modifying benefits from exercising most days of the week. (See "Exercise prescription and guidance for adults", section on 'Writing the aerobic exercise prescription'.)

Ultrasound screening for tendinopathy in asymptomatic athletes (February 2025)

The utility of ultrasound for identifying lesions that put asymptomatic athletes at risk of future injury remains unclear. In a systematic review and meta-analysis of 16 studies of asymptomatic, young adult athletes, including assessments of 810 Achilles and 1156 patellar tendons, abnormal ultrasound findings predicted the development of symptoms consistent with tendinopathy in only 27 percent of participants, while 92 to 93 percent of athletes without abnormalities remained symptom-free [66]. Ultrasound assessment may have a role in select athletes at high risk (eg, those with prior injury), but available evidence does not justify population-based screening. (See "Achilles tendinopathy", section on 'Diagnostic imaging' and "Patellar tendinopathy", section on 'Ultrasound'.)

PRIMARY CARE PULMONOLOGY

Catheter-directed therapies for intermediate-risk pulmonary embolism (June 2025)

The optimal catheter-directed therapy (CDT) for patients with an intermediate risk of death from pulmonary embolism (PE) is unclear. A recent randomized trial of 550 patients with intermediate-risk PE who were candidates for CDT compared catheter-directed thrombolysis with catheter-directed suction thrombectomy [67]. Suction thrombectomy resulted in lower rates of clinical deterioration/bailout therapy (1.8 versus 5.4) and intensive care use (46 versus 99 percent) than thrombolysis; patients were also less dyspneic and fewer patients had moderate or severe right ventricle dysfunction at 24 hours (42 versus 58 percent). However, at 30 days, mortality and dyspnea scores were similar. Although catheter-directed suction thrombectomy is our preference and has several advantages including faster resolution of thrombus, choosing among these modalities also depends upon local expertise. (See "Acute pulmonary embolism in adults: Reperfusion therapy in intermediate- and high-risk patients", section on 'Suction/mechanical embolectomy'.)

Methotrexate as initial therapy for symptomatic, moderate-to-severe pulmonary sarcoidosis (June 2025)

Pulmonary sarcoidosis is usually treated initially with oral glucocorticoids, which have numerous side effects. In a new open-label trial of 138 treatment-naïve patients with pulmonary sarcoidosis and moderate-to-severe symptoms, impaired lung function, or disease progression over the last 12 months, patients randomly assigned to weekly oral methotrexate monotherapy for 24 weeks had similar lung function improvement compared with patients assigned to prednisone (6.2 versus 5.7 percentage point improvement in predicted forced vital capacity) [68]. Methotrexate had a slower onset of action but was associated with less weight gain (1.1 versus 5.0 kg) and similar patient satisfaction by the end of the trial. Based in part on this evidence, we now suggest methotrexate as initial therapy for most patients with moderate-to-severe pulmonary sarcoidosis requiring treatment; concurrent oral glucocorticoids are appropriate for those with rapidly progressing disease. (See "Treatment of pulmonary sarcoidosis: Initial approach", section on 'Efficacy of methotrexate'.)

Add-on therapy for refractory COPD in patients with peripheral eosinophilia (June 2025)

The use of biologics targeting type 2 inflammation in chronic obstructive pulmonary disease (COPD) has demonstrated promise, with approval of dupilumab in 2024 and new approval of mepolizumab for patients with eosinophilia and exacerbations despite inhaled therapies. Mepolizumab approval followed a trial of over 800 patients with COPD, peripheral hypereosinophilia (≥300 cells/microL), and exacerbations despite triple inhaled therapy (long-acting muscarinic antagonist, long-acting beta agonist, and inhaled corticosteroid). Those randomized to treatment with the anti-interleukin 5 monoclonal antibody mepolizumab (100 mg subcutaneously monthly) had a reduction in moderate or severe exacerbations compared with placebo (0.80 versus 1.01 events per year), but no improvements in lung function or respiratory symptoms [69]. Similar patients treated with dupilumab have shown a somewhat larger reduction in exacerbation rates and modest improvements in lung function and symptoms. Absent comparative trials, we now suggest either dupilumab or mepolizumab for patients with COPD and peripheral eosinophilia who have persistent exacerbations despite optimized inhaled therapy (algorithm 2). (See "Management of refractory chronic obstructive pulmonary disease", section on 'Mepolizumab'.)

Anti-inflammatory reliever therapy in patients with mild asthma (May 2025)

As-needed inhaled glucocorticoids reduce asthma exacerbations in those with poor control despite multiple maintenance therapies, but whether this practice benefits patients with more mild disease has been unclear. In a trial that enrolled over 2400 patients with poor asthma control on albuterol alone (71 percent) or low-dose inhaled glucocorticoids, use of albuterol-budesonide as needed reduced the risk of exacerbations requiring systemic glucocorticoids compared with albuterol as-needed alone (5.3 versus 9.4 percent; hazard ratio 0.54) [70]. However, given their poor asthma control at baseline, all patients enrolled in this study would qualify for a step-up in asthma therapy, which was not initiated in the control group. These results support our recommendation for anti-inflammatory reliever therapy as a preferred initial controller option for patients with asthma who have moderately frequent symptoms. (See "Initiating asthma therapy and monitoring in adolescents and adults", section on 'As-needed low-dose ICS and SABA (step 1)'.)

Factors increasing risk of poor respiratory outcomes in those without airway obstruction (May 2025)

A new "multidimensional diagnostic framework" proposes to define chronic obstructive pulmonary disease (COPD) based on the presence of respiratory symptoms and imaging findings (table 6) rather than relying on spirometry [71]. This study identified over 800 patients enrolled in the COPDGene cohort who lacked obstruction on spirometry, but were classified as having COPD using these new criteria. These reclassified patients had an approximately twofold increased risk of all-cause mortality and respiratory exacerbations over a median 10-year follow-up compared with participants who lacked clinical or imaging evidence of COPD. While this proposed framework helped identify patients at risk for poor respiratory outcomes, patients without obstruction remained at lower risk than those meeting current COPD diagnostic criteria (ie, spirometric obstruction and compatible pulmonary symptoms); they may also represent a heterogenous group with different respiratory pathologies. We continue to use traditional criteria to diagnose COPD until there is more research to better understand and treat these non-obstructed patients. (See "Chronic obstructive pulmonary disease: Diagnosis and staging", section on 'Interrelationships among these conditions'.)

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 [72]. 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'.)

PRIMARY CARE PSYCHIATRY

Misuse of prescribed stimulant medications in adults (May 2025)

Stimulant medications, such as amphetamines and methylphenidate, are commonly prescribed to treat attention deficit hyperactivity disorder, but the rates of misuse of these medications are unclear. In a nationally representative sample of almost 84,000 adults in the United States, prescription stimulant misuse and prescription stimulant use disorder occurred commonly in patients prescribed stimulants (25 percent and 9 percent, respectively) [73]. The use of amphetamines was associated with a higher prevalence of misuse and use disorder (32 and 11 percent) than the use of methylphenidate (10 and 5 percent). Clinicians should carefully weigh the benefits and risks of these medications and regularly monitor patients receiving them for misuse and the development of stimulant use disorder. (See "Prescription drug misuse: Epidemiology, prevention, identification, and management", section on 'Misuse'.)

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) [74]. 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'.)

Bright light therapy in nonseasonal major depression (February 2025)

Although bright light therapy is a standard treatment for seasonal affective disorder, its efficacy for nonseasonal major depression has been less certain. In a recent meta-analysis of eight randomized trials involving 547 participants with nonseasonal depression, bright light therapy (eg, 10,000 lux for 30 minutes for four weeks) resulted in a greater remission rate than control interventions (typically dim red light; 41 versus 24 percent) [75]. Inclusion of individuals with both unipolar and bipolar depression limited the certainty of these findings. In individuals with nonseasonal major depression, we suggest bright light therapy as an adjunct to pharmacotherapy and/or psychotherapy. (See "Major depressive disorder in adults: Treatment with supplemental interventions", section on 'Bright light therapy'.)

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 [76]. 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'.)

PRIMARY CARE RHEUMATOLOGY

Risk of rheumatoid arthritis in patients with arthralgias (June 2025)

Which patients presenting with arthralgias are at highest risk of developing rheumatoid arthritis is unclear. In a pooled analysis of over 2000 patients presenting with arthralgias from 10 cohorts, a risk stratification tool incorporating six clinical and serologic features (ie, morning stiffness, patient-reported joint swelling, difficulty making a fist, C-reactive protein, rheumatoid factor, and anti-citrullinated peptide antibody) predicted patients presenting with arthralgias who would develop an inflammatory arthritis with good diagnostic accuracy; accuracy was improved if magnetic resonance imaging-detected subclinical inflammation was added to the model [77]. Adding ultrasound imaging of the joints did not significantly improve the predictive value of the tool. This model may identify which patients presenting with arthralgias merit close follow-up and/or early therapy with immunosuppressive agents but requires validation. (See "Undifferentiated inflammatory arthritis in adults", section on 'Differential diagnosis'.)

Increased risk of gout flare after discontinuing prophylactic therapy (June 2025)

Patients with gout typically receive prophylactic antiinflammatory medications to prevent flares when initiating or intensifying urate-lowering therapy, but the optimal approach to this practice is not clear. In a meta-analysis that included over 2900 patients who received prophylaxis while starting or increasing urate-lowering therapy, 15 percent of patients flared while receiving prophylaxis [78]. In the three months after stopping prophylaxis, 30 percent of patients flared; during the final study period, only 12 percent of patients flared. The relapse risk was not significantly influenced by the duration of prophylaxis or the type of urate-lowering therapy. When patients with gout discontinue prophylactic antiinflammatory therapy, providers should counsel them on how to manage this transient increased risk of relapse. (See "Gout: Pharmacologic urate-lowering therapy and treatment of tophi", section on 'Duration of prophylactic therapy'.)

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 [79]. 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'.)

Risk of rheumatoid arthritis in patients with arthralgias (April 2025)

Patients presenting with arthralgias and seropositivity (ie, the presence of anti-citrullinated protein antibodies (ACPA) and/or rheumatoid factor (RF) are presumed to be at risk of progression to rheumatoid arthritis (RA), but the magnitude of risk has been unclear. In a prospective cohort of over 600 seropositive patients presenting with arthralgias, approximately one-third of patients were diagnosed with RA after a mean follow-up of approximately four years [80]. Risk factors for progression to RA included morning stiffness, high titer ACPA, double-positivity for ACPA and RF, and having a first-degree relative with RA. Patients with arthralgias who have these characteristics should be monitored closely for the development of RA. (See "Undifferentiated inflammatory arthritis in adults", section on 'Prognosis'.)

OTHER ADULT PRIMARY CARE

Strategies for quitting smokeless tobacco products (June 2025)

Smokeless tobacco products, such as chewing tobacco and snuff/snus pouches, cause nicotine addiction and pose health risks; however, the optimal approach for stopping their use is unclear. A recent meta-analysis suggested that smokeless tobacco quit rates were higher with varenicline and nicotine replacement therapy but not bupropion, when compared with placebo [81]. Quit rates were also higher with counseling and brief advice, compared with control interventions (minimal to no support). These results underscore that strategies with efficacy for smoking cessation are also useful for helping patients stop using smokeless tobacco products. (See "Overview of smoking cessation management in adults", section on 'Treatment considerations for specific populations'.)

New tinnitus management guidelines (June 2025)

The US Department of Veterans Affairs/US Department of Defense Tinnitus Clinical Practice Guideline Work Group has published new guidelines on the management of tinnitus [82]. Recommended treatment options include educational counseling, hearing amplification for those with hearing loss, sound-based interventions (ie, "masking"), behavioral interventions (eg, cognitive behavioral therapy), or a combination of these. They advise against the use of pharmacotherapy or supplements for the treatment of tinnitus and call for further research to establish the efficacy of various options. These recommendations are overall consistent with our management approach. (See "Treatment of tinnitus", section on 'Limited role for medications'.)