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.

PREVENTION

Reducing alcohol use during pregnancy (May 2024)

Clinicians caring for pregnant persons are advised to routinely educate and counsel about the harms of alcohol use during pregnancy. A meta-analysis of three trials reported more pregnant patients continuously abstained from alcohol consumption after receiving psychosocial interventions compared with usual care (69 versus 51 percent) [1]. We encourage clinicians caring for pregnant individuals to offer access to psychosocial interventions (eg, information sessions, self-help groups, cognitive behavioral therapy) in addition to routinely educating them about the dangers of alcohol use during pregnancy. (See "Alcohol intake and pregnancy", section on 'Management of screen-positive pregnant persons'.)

IMMUNIZATIONS

Second dose of a 2023-2024 COVID-19 vaccine for individuals 65 years and older (April 2024)

In the United States, a single dose of an updated 2023-2024 formula COVID-19 vaccine is recommended for all immunocompetent adults and adolescents, regardless of prior vaccination history. In February 2024, the Centers for Disease Control and Prevention (CDC) updated its guidance to recommend a second dose (at least four months after the prior dose) for individuals 65 years and older [2]. Rates of COVID-19-associated hospitalization and death are higher in this age group than in any other, and the repeat dose is intended to improve protection by restoring the waning immune response; the 2023-2024 vaccine elicits response against currently circulating variants. Our recommendations are consistent with those of the CDC. (See "COVID-19: Vaccines", section on 'Adults 65 years and older'.)

2024 immunization schedule for adults (January 2024)

The United States Centers for Disease Control and Prevention has published the 2024 immunization schedule for adults (figure 1 and figure 2) [3]. Respiratory syncytial virus (RSV) vaccine is a new addition to the schedule; it is recommended for pregnant people 32 to 36 weeks' gestation during RSV season and is an option for adults ≥60 years of age. Mpox vaccine has also been added and is recommended for adults of all ages who are at risk for infection. Other changes include updates to COVID-19, polio, and meningococcal vaccine recommendations. Our approach to immunization is largely consistent with these updated recommendations. (See "Standard immunizations for nonpregnant adults", section on 'Immunization schedule for nonpregnant adults'.)

GENERAL INTERNAL MEDICINE

Smoking cessation strategies after failing initial pharmacotherapy (May 2024)

Several medications are effective for smoking cessation; however, optimal management of individuals who do not abstain with initial pharmacotherapy has been unclear. In a recent trial, participants who smoked at least five cigarettes daily and had previously been randomized to receive six weeks of varenicline (2 mg daily) or combination nicotine replacement therapy (NRT; 21 mg/day patch plus lozenges) but did not quit smoking were re-randomized to continue the same medication dose, increase the dose, or switch medications [4]. Among those who initially received varenicline, 12-week quit rates were highest with increasing the dose to 3 mg daily, compared with continuing the 2 mg dose or switching to NRT (20, 3, and 0 percent, respectively). Among those who initially received NRT, quit rates with increased dosing (two 21 mg/day patches) or switching to varenicline were higher than continuing standard dosing (14, 14, and 8 percent, respectively). These results suggest that for patients unable to quit with standard-dose varenicline or NRT, using higher doses is an effective option. (See "Pharmacotherapy for smoking cessation in adults", section on 'No response to treatment'.)

Acetaminophen use in pregnancy not associated with adverse neurodevelopment in offspring (April 2024)

Although older studies raised concerns about a possible adverse association between in utero exposure to acetaminophen and neurodevelopment, more recent studies with a lower risk of bias have not reported an association. In a population-based study in which acetaminophen use was prospectively recorded, siblings with any in utero exposure had no increased risk for attention deficit hyperactivity disorder, autism spectrum disorder, or intellectual disability at age 10 years compared with their unexposed siblings [5]. Although an association cannot be definitively excluded, these data are reassuring when a short course of acetaminophen is desirable to manage pain or fever during pregnancy. (See "Prenatal care: Patient education, health promotion, and safety of commonly used drugs", section on 'Acetaminophen'.)

Congenital anomaly risk with methadone or buprenorphine exposure (April 2024)

Data regarding the teratogenic risk of medications for opioid use disorder (MOUD) are limited. In a population-based study comparing over 9500 pregnancies exposed to buprenorphine in the first trimester with nearly 3900 methadone-exposed pregnancies, buprenorphine use was associated with a lower overall risk of congenital anomalies (5 versus 6 percent) [6]. Although the analysis adjusted for multiple potential confounding factors, unmeasured confounders may explain some of the observed associations. We base the choice of buprenorphine versus methadone for MOUD on other factors (table 1). (See "Opioid use disorder: Pharmacotherapy with methadone and buprenorphine during pregnancy", section on 'Risk of structural anomalies'.)

Electronic cigarettes for smoking cessation (March 2024)

Electronic cigarettes have played an uncertain role in smoking cessation because of a paucity of data regarding their efficacy and safety. However, recent randomized trials suggest that e-cigarettes are efficacious in helping adults stop smoking [7,8]. In a meta-analysis of seven randomized trials, nicotine e-cigarettes resulted in higher quit rates than nicotine replacement therapy (17.5 versus 10.2 percent) [9]. Rates of adverse events were similar between groups. Nicotine e-cigarettes also appear more effective than usual care, behavioral counseling, and nonnicotine e-cigarettes [9]. Although questions regarding their long-term safety remain, these data suggest a role for e-cigarettes as a smoking cessation aid, particularly for patients who have not had success with standard pharmacotherapies. (See "Vaping and e-cigarettes", section on 'Efficacy'.)

PRIMARY CARE ALLERGY AND IMMUNOLOGY

Chronic inducible urticaria (April 2024)

The term chronic inducible urticaria (CIndU) refers to distinct disorders in which urticaria is elicited by identifiable physical triggers (eg, firm pressure, shifts in body temperature, cold, heat, sun, water, or vibration). CIndU can exist in isolation or together with chronic spontaneous urticaria (CSU), but data about CIndU are limited. In a retrospective review of over 400 children and adults with CIndU, those with isolated CIndU had fewer episodes of angioedema, emergency referral, need for systemic glucocorticoids, and coexistent systemic disorders compared with patients with both CIndU and CSU, providing some useful information about the relative severity of these disorders [10]. (See "Physical (inducible) urticaria", section on 'Severity'.)

PRIMARY CARE CARDIOVASCULAR MEDICINE

Phosphodiesterase-5 inhibitors and cardiovascular disease (March 2024)

Erectile dysfunction is common among individuals with established cardiovascular disease and is independently associated with future cardiovascular events in those without cardiovascular disease. Updated recommendations from the Princeton IV conference on phosphodiesterase-5 (PDE-5) inhibitors and cardiac health provide guidance on cardiovascular risk stratification of individuals with erectile dysfunction and the management of erectile dysfunction in men with cardiovascular disease [11]. The guidelines emphasize that in men with cardiovascular disease and erectile dysfunction who are prescribed nitrates, clinicians should assess the patient's current need for nitrate therapy, consider nitrate deprescription, and determine whether PDE-5 inhibitors can safely be prescribed. These guidelines help clinicians evaluate and manage men with erectile dysfunction and cardiovascular disease. (See "Sexual activity in patients with cardiovascular disease", section on 'Coadministration with nitrates contraindicated'.)

The Preventing Risk of Cardiovascular Disease EVENTS (PREVENT) calculator (February 2024)

Guidelines for primary prevention of cardiovascular disease (CVD) recommend using a risk calculator to estimate atherosclerotic CVD (ASCVD) risk. However, risk calculators derived from older databases may not reflect current risk in diverse populations. To provide contemporary estimates of ASCVD risk, the PREVENT calculator was derived and validated in over 6.6 million adults to estimate 10- and 30-year risks of CVD and its subtypes, heart failure and ASCVD [12,13]. The PREVENT calculator inputs include standard CVD risk measures (eg, age, sex, body mass index, diabetes, lipid levels, smoking history, blood pressure, and kidney function); the full model also includes albuminuria, hemoglobin A1C, and zip code (which estimates social deprivation). The PREVENT calculator is a valuable tool for individualizing risk assessment and discussing the primary prevention of ASCVD with patients. (See "Atherosclerotic cardiovascular disease risk assessment for primary prevention in adults: Our approach", section on 'Choosing a risk calculator'.)

PRIMARY CARE ENDOCRINOLOGY AND DIABETES

Glucagon-like peptide 1 receptor agonist use and thyroid cancer risk (April 2024)

Preclinical studies suggest that glucagon-like peptide 1 (GLP-1) receptor agonists may increase risk of thyroid neoplasia, but whether clinical use of these agents increases thyroid cancer risk is uncertain. A recent cohort study evaluated thyroid cancer incidence in individuals initiating treatment with a GLP-1 receptor agonist (predominantly liraglutide and semaglutide) compared with a dipeptidyl peptidase 4 (DDP-4) inhibitor. After a mean follow-up of 3.9 years, GLP-1 receptor agonist use was not associated with an increased risk of any thyroid cancer or medullary thyroid cancer [14]. DPP-4 inhibitors raise endogenous GLP-1 levels and therefore may not be an optimal comparator. Until more data are available, this study does not change our practice of avoiding GLP-1-based therapies in individuals with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2A or 2B. (See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Other'.)

Continuous glucose monitoring in individuals with type 2 diabetes (April 2024)

In individuals with type 2 diabetes, the utility of continuous glucose monitoring (CGM) is uncertain. In a meta-analysis of 14 trials in 1647 people with type 2 diabetes not meeting glycemic goals (variably defined, usually A1C ≥7, 7.5, or 8 percent), use of either flash or real-time CGM modestly reduced A1C compared with fingerstick blood glucose monitoring (BGM; mean difference -0.32 percentage points) [15]. Most participants were taking oral glucose-lowering medications with or without insulin, and trial duration varied from 10 to 52 weeks. In a separate meta-analysis with similar trial durations, CGM similarly reduced A1C [16]. In individuals with type 2 diabetes and A1C above target, CGM provides modest glycemic benefit. In this population, CGM may be helpful in identifying glycemic patterns that direct changes in behaviors and/or pharmacologic therapy. (See "Glucose monitoring in the ambulatory management of nonpregnant adults with diabetes mellitus", section on 'Insulin treated'.)

Tirzepatide for weight loss in adults (March 2024)

The US Food and Drug Administration recently approved subcutaneous tirzepatide, a dual glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, for chronic weight management [17]. Two randomized trials in adults with obesity demonstrated mean losses of 15 to 21 percent body weight with the highest dose of tirzepatide (15 mg weekly) [18,19]. In the larger of the two trials, over 80 percent of participants in all tirzepatide treatment groups (5 to 15 mg weekly) lost ≥5 percent of body weight, compared with 35 percent of those assigned to placebo [18]. Dose-related gastrointestinal side effects (nausea, diarrhea, constipation) were common but generally mild. Although direct comparisons are limited, the magnitude of weight loss with tirzepatide appears greater than that with other agents; thus, we consider tirzepatide a preferred medication for chronic weight management. (See "Obesity in adults: Drug therapy", section on 'Efficacy for weight loss'.)

Noninsulin antidiabetic medications and pregnancy (February 2024)

Noninsulin antidiabetic medications such as glucagon-like peptide 1 (GLP-1) agonists, sodium-glucose cotransporter 2 (SGLT-2) inhibitors, and dipeptidyl peptidase 4 (DPP-4) inhibitors are commonly used in nonpregnant individuals but avoided in pregnancy because of lack of safety data in humans and harms observed in animal studies. However, in a multinational population-based cohort study including nearly 2000 individuals with preconception/first trimester exposure to these medications, the frequency of congenital anomalies was not increased compared with insulin [20]. A limitation of the study is that it did not adjust for potential differences in A1C, diabetes severity, or diabetes duration, which could obscure true effects on risk for congenital anomalies. We continue to avoid use of GLP-1 agonists, SGLT-2 inhibitors, and DPP-4 inhibitors in females planning to conceive and in pregnancy. (See "Pregestational (preexisting) diabetes: Preconception counseling, evaluation, and management", section on 'Patients on preconception noninsulin antihyperglycemic agents'.)

Monitoring after negative confirmatory testing for primary aldosteronism (February 2024)

After a positive screening test for primary aldosteronism, confirmatory testing is required for diagnosis. In individuals with a positive screening test but negative confirmatory testing, the optimal monitoring strategy is uncertain. In a study that prospectively followed 184 individuals with a positive screening test for primary aldosteronism but negative confirmatory testing, a screening test was repeated after at least two years of follow-up [21]. If positive, confirmatory testing was performed again. Over a mean follow-up of five years, 20 percent of participants were diagnosed with primary aldosteronism. Those who developed primary aldosteronism exhibited higher blood pressure between initial and repeat testing despite similarly aggressive antihypertensive therapy. These findings support repeat testing for primary aldosteronism in individuals with initially negative confirmatory testing, particularly in those with progressively treatment-refractory blood pressure. (See "Diagnosis of primary aldosteronism", section on 'Negative confirmatory testing'.)

Effects of tirzepatide discontinuation on weight (February 2024)

Glucagon-like peptide 1-based therapies for the treatment of obesity result in substantial weight loss. Although earlier data suggested that stopping treatment with semaglutide results in weight regain, it was unclear whether the same occurs with tirzepatide. Among adults with obesity who had previously lost weight (21 percent mean weight reduction) during a 36-week, open-label trial of tirzepatide, those randomly assigned to continue tirzepatide for 52 weeks experienced additional weight loss, whereas those assigned to placebo partially regained (-5.5 versus +14 percent mean weight change, respectively) [22]. These results, in line with those of previous studies, suggest that most individuals with obesity who opt for pharmacotherapy will require long-term treatment for weight loss maintenance. (See "Obesity in adults: Drug therapy", section on 'Duration of therapy'.)

Semaglutide and cardiovascular outcomes (January 2024)

Semaglutide and other glucagon-like peptide 1 receptor agonists can reduce rates of adverse cardiovascular events in individuals with type 2 diabetes who have established cardiovascular disease or are at high risk of cardiovascular disease. In a newly published trial of 17,604 individuals with overweight or obesity and cardiovascular disease but not diabetes, once-weekly subcutaneous semaglutide 2.4 mg reduced rates of adverse cardiovascular outcomes compared with placebo (6.5 versus 8.0 percent) [23]. Discontinuation of the study drug due to side effects occurred more often with semaglutide (17 versus 8 percent). For individuals with overweight or obesity and established cardiovascular disease, semaglutide is a particularly attractive option for chronic weight management. (See "Obesity in adults: Drug therapy", section on 'Cardiovascular benefits'.)

PRIMARY CARE GASTROENTEROLOGY

Resmetirom for metabolic dysfunction-associated steatohepatitis (MASH) (April 2024)

Therapeutic options for adults with metabolic dysfunction-associated steatohepatitis (MASH) are expanding. In a trial comparing two doses of resmetirom (a thyroid hormone receptor-beta agonist) with placebo in nearly 1000 adults with MASH and liver fibrosis stage F1B, F2, or F3, resmetirom resulted in higher rates of MASH resolution at 52 weeks (100 mg, 80 mg, placebo: 30, 26, and 10 percent, respectively) [24]. Resmetirom also increased the percentage of patients in whom fibrosis improved by at least one stage (100 mg, 80 mg, placebo: 26, 24, and 14 percent, respectively). However, the treatment groups had more diarrhea and nausea. We anticipate using resmetirom as an option for patients with MASH and F2 or F3 fibrosis who do not achieve sustained weight loss. (See "Management of metabolic dysfunction-associated steatotic liver disease (nonalcoholic fatty liver disease) in adults", section on 'Pharmacologic therapies'.)

Dupilumab for refractory eosinophilic esophagitis (February 2024)

Few data are available on the use of dupilumab (a monoclonal antibody) for treating refractory eosinophilic esophagitis. In a cohort study of 46 patients with refractory eosinophilic esophagitis, dupilumab therapy was associated with histologic remission (defined as <15 eosinophils/high-power field) in 37 patients (80 percent) and with symptomatic improvement in 42 patients (91 percent) after a median of six months [25]. These data support our approach of using dupilumab for patients with eosinophilic esophagitis who have not responded to other therapies (eg, topical glucocorticoids). (See "Treatment of eosinophilic esophagitis (EoE)", section on 'Dupilumab'.)

Mortality risk in alcohol-associated liver disease (January 2024)

Few studies have reported the long-term outcomes of patients with alcohol-associated liver disease (ALD). In a national registry study including over 23,000 patients with ALD diagnosed at median age 58 years, 67 percent died during >100,000 person-years of follow-up and liver disease was the primary cause of death in 45 percent [26]. The 5- and 10-year mortality rates due to liver disease were 26 and 31 percent, respectively. These data emphasize the importance of treating patients with alcohol use disorder and may inform strategies to prevent liver-related mortality in those with ALD. (See "Management of alcohol-associated steatosis and alcohol-associated cirrhosis", section on 'Mortality'.)

PRIMARY CARE GERIATRICS

Point-of-care decision support tool for older adult care (February 2024)

Overtesting and overtreatment can lead to adverse health outcomes in older adults. In a trial conducted among 60 outpatient practices, a point-of-care, clinical decision support tool utilizing behavioral principles plus brief case-based education resulted in lower annual rates of three outcomes (prostate-specific antigen testing in men aged 76 years and older without previous prostate cancer, urine testing for nonspecific reasons in women aged 65 years and older, and overtreatment of diabetes in patients aged 75 years and older) when compared with brief case-based education alone [27]. Clinical decision support tools may aid in preventing unnecessary testing and treatments. (See "Geriatric health maintenance", section on 'Appropriate goals of care for older adults'.)

PRIMARY CARE GYNECOLOGY

Same-day contraceptive start and pregnancy risk (May 2024)

Individuals who desire contraception often want to start the method on the same day as their office visit, but the risk of pregnancy for those >7 days from the onset of their last menstrual period has been a concern. However, in a prospective study of over 3500 individuals seeking hormonal contraception, first-cycle unintended pregnancy rates were low for both those with same-day starts >7 days from the onset of menses and those who waited to start the method within 7 days of onset of menses (0.4 and 0.1 percent, respectively), even though approximately 20 percent of same-day start participants had at least one episode of unprotected intercourse within the prior 14 days [28]. For individuals who prefer a same-day start and understand the potential need for follow-up pregnancy testing, hormonal contraceptives (any method) may be started on the same day as the visit with low overall pregnancy risk. (See "Contraception: Counseling and selection", section on 'Starting a method'.)

Macular changes related to pentosan polysulfate sodium (November 2023)

Macular eye disease has been reported in patients who have taken pentosan polysulfate sodium (PPS), which is used for the treatment of interstitial cystitis. In a prospective cohort study of 26 eyes with PPS maculopathy and >3000 g cumulative PPS exposure, progression of macular changes continued 13 to 30 months after drug cessation [29]. Median visual acuity decreased slightly; most patients reported progression of symptoms, including difficulty in low-light environments and blurry vision. These results indicate that PPS maculopathy progresses despite drug discontinuation, underscoring the importance of regular screening for maculopathy in patients with current or prior PPS exposure. (See "Interstitial cystitis/bladder pain syndrome: Management", section on 'Pentosan polysulfate sodium as alternative'.)

PRIMARY CARE HEMATOLOGY AND ONCOLOGY

Breast cancer-specific mortality in male breast cancer (April 2024)

Studies are evaluating prognosis of male breast cancer. In a cohort study including 2836 men with early, hormone receptor-positive breast cancer, the 20-year risk of breast cancer-specific mortality was 12 percent for stage I disease, 26 percent for stage II disease, and 46 percent for stage III disease [30]. There was an increase in late recurrences as nodal involvement increased, such that a bimodal distribution was present for those with N3 and stage III disease peaking at 4 and 11 years. Higher stage, grade, and age were all associated with higher risks. These estimates are helpful in counseling males with early, hormone receptor-positive breast cancer. (See "Breast cancer in men", section on 'Prognosis'.)

Intravenous iron in heart failure (April 2024)

Individuals with heart failure (HF) and iron deficiency should be treated, but expert groups differ on the perceived benefits. In a new meta-analysis that included over 4500 patients participating in randomized trials, intravenous iron reduced the rate of cardiovascular hospitalizations compared with placebo; all-cause mortality was not reduced [31]. This supports our suggested approach of using intravenous iron, although oral iron may be reasonable. Iron supplementation should be stopped once stores are repleted, as excess iron deposition is cardiotoxic. (See "Evaluation and management of anemia and iron deficiency in adults with heart failure", section on 'Iron supplementation'.)

Mirtazapine in patients with cancer-related anorexia (April 2024)

Patients with advanced cancer are at risk for cancer-related anorexia and weight loss; studies are evaluating strategies to manage these issues. In a randomized trial in 86 patients with advanced non-small cell lung cancer, mirtazapine improved mean daily energy intake by 379 kcal versus placebo and reduced the proportion of patients with sarcopenia (57 versus 83 percent), although appetite scores were not higher [32]. Despite these results, previous data are inconsistent. As such, we prefer other strategies including dietary counseling and olanzapine for cancer-related anorexia. (See "Management of cancer anorexia/cachexia", section on 'Mirtazapine'.)

Improvement in breast cancer mortality from 1975 to 2019 (January 2024)

Improvements in breast cancer screening and treatments are decreasing breast cancer mortality. In a study using four simulation models of breast cancer mortality rates in the United States (US), breast cancer screening and treatment in 2019 were associated with a 58 percent reduction in US breast cancer mortality compared with 1975 [33]. Approximately half of this reduction was due to treatment of early breast cancer, while the rest was divided roughly equally between treatment of metastatic breast cancer and breast cancer screening. We support breast cancer screening for appropriate candidates and incorporate novel, data-driven strategies into our treatment recommendations for breast cancer. (See "Overview of the treatment of newly diagnosed, invasive, non-metastatic breast cancer", section on 'Introduction' and "Screening for breast cancer: Strategies and recommendations".)

PRIMARY CARE INFECTIOUS DISEASES

Pivmecillinam for acute simple cystitis (May 2024)

In 2024, the US Food and Drug Administration approved a beta-lactam antibiotic, pivmecillinam, for treatment of acute simple cystitis in female adults [34]. Pivmecillinam is one of our preferred options for treatment of cystitis and has long been used in certain European countries because it is less likely than other agents to select for resistant isolates. It also retains activity against many extended-spectrum beta-lactamase-producing organisms. The recommended dose and formulation vary by region, and data do not clearly demonstrate better clinical outcomes with one versus the other. For empiric therapy, we would generally use 185 mg pivmecillinam base (equivalent to 200 mg pivmecillinam hydrochloride) orally three times daily for three to seven days, which is the dose recommended in the United States. (See "Acute simple cystitis in adult and adolescent females", section on 'First-line antimicrobial options'.)

Limited benefit of nirmatrelvir-ritonavir in non-high-risk individuals with mild-to-moderate COVID-19 (May 2024)

Although nirmatrelvir-ritonavir reduces COVID-19-associated hospitalization and death in patients at high risk for severe disease, the benefit in lower-risk patients is uncertain. The EPIC-SR trial evaluated nirmatrelvir-ritonavir among 1200 outpatients who either had no risk factors for severe disease (and were unvaccinated or vaccinated) or had at least one risk factor but were vaccinated; median age was 42 years, and only 5 percent were 65 years old or older [35]. In the trial, nirmatrelvir-ritonavir did not reduce duration of symptoms, the risk of hospitalization from COVID-19, or all-cause mortality compared with placebo. We continue to suggest against treating patients who are not at high risk for severe disease. (See "COVID-19: Management of adults with acute illness in the outpatient setting", section on 'Efficacy and rationale'.)

Hepatitis C virus antiviral treatment for patients with opioid use disorder (May 2024)

Despite concerns about adherence to antiviral therapy among individuals with opioid use disorder, hepatitis C virus (HCV) treatment can be highly successful in this population, particularly in nontraditional care settings. In a cluster-randomized trial that included 600 individuals with chronic HCV infection who were engaged in an opioid treatment program, provision of antiviral therapy through the program, directed by an HCV specialist over telemedicine, increased rates of antiviral initiation (92 versus 40 percent) and sustained virologic response (85 versus 30 percent) compared with traditional referral to a specialist clinic for treatment [36]. These data highlight the impact of reducing barriers to care for individuals with opioid use disorder and support our recommendation to treat all patients for chronic HCV, regardless of active drug use. (See "Patient evaluation and selection for antiviral therapy for chronic hepatitis C virus infection", section on 'Active drug use'.)

Pemivibart for prevention of COVID-19 in selected immunocompromised patients (April 2024)

Monoclonal antibodies have been used as adjunctive pre-exposure prophylaxis to reduce the risk of COVID-19 in individuals expected to have suboptimal response to vaccination, although emergence of variants that escape neutralization limit their utility. In March 2024 in the United States, the novel monoclonal antibody pemivibart received emergency use authorization (EUA) to prevent COVID-19 in individuals age 12 years or older (weighing at least 40 kg) who have moderate-to-severe immunocompromising conditions (table 2) [37]. Pemivibart is active against JN.1, the dominant SARS-CoV-2 variant. We suggest pemivibart in individuals at the highest risk for vaccine nonresponse (eg, those with hematologic malignancy or recent history of transplantation) as long as it remains active against the main circulating variants. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Limited role for monoclonal antibodies in selected patients'.)

Demographic disparities in tuberculosis incidence among US-born individuals (April 2024)

In the United States (US), the incidence of tuberculosis (TB) is increased among certain populations. A study including national TB registry data for 2011 to 2021 among US-born individuals found that, compared with individuals who identify as White, TB incidence rate ratios were 4.4 to 14.2 times higher among individuals who self-identified as American Indian/Alaska Native, Asian, Black, or Hispanic [38]. Genotyping data suggested an important role of recent transmission in the observed disparities, supporting the need for timely identification and prevention of ongoing chains of transmission. These findings warrant targeted efforts by TB prevention and control programs. (See "Epidemiology of tuberculosis", section on 'In the United States'.)

Precautions for individuals with COVID-19 in the community (April 2024)

In March 2024, the United States Centers for Disease Control and Prevention updated guidance for precautions for people with COVID-19 in the community [39]. Such individuals should stay at home until their symptoms are improving and they have been afebrile for 24 hours without the use of antipyretics. They can subsequently resume normal activities but are encouraged to use other precautions (eg, masking, social distancing, good ventilation) for an additional five days to further reduce the risk of transmission to others. These measures are particularly important when around persons who are at increased risk for severe disease (eg, advanced age, immunocompromise, cardiopulmonary disease). (See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection".)

Ensitrelvir for mild to moderate COVID-19 (March 2024)

Although nirmatrelvir-ritonavir reduces hospitalization and death from COVID-19,drug interactions preclude its use in some patients. Ensitrelvir is an oral protease inhibitor that prevents SARS-CoV-2 replication and has fewer drug interactions. In a randomized, double-blinded trial of over 1800 patients with mild to moderate COVID-19 (majority vaccinated) in Asia in early 2022, five days of ensitrelvir reduced time to symptom resolution by one day compared with placebo [40]. Since only two participants (one in each arm) had a COVID-19-related hospitalization within the 28-day study period, it is unknown whether the drug prevents hospitalizations or death from COVID-19. Ensitrelvir is approved for emergency use in Japan; it is undergoing US Food and Drug Administration approval process in the United States. (See "COVID-19: Management of adults with acute illness in the outpatient setting", section on 'Therapies of limited or uncertain benefit'.)

Simnotrelvir-ritonavir for mild to moderate COVID-19 (January 2024)

Although nirmatrelvir-ritonavir reduces hospitalization and death from COVID-19, the many drug interactions make it difficult to use in some patients. Simnotrelvir-ritonavir is a similar protease inhibitor combination that inhibits viral replication but does not have as many drug interactions. In a randomized, double-blinded study of over 1000 patients with mild to moderate COVID-19 (majority fully vaccinated), 5 days of simnotrelvir-ritonavir reduced time to symptom resolution by 1.5 days [41]. Since no participant progressed to severe disease or died by day 29, it is unknown whether the drug prevents hospitalizations or death from COVID-19. Simnotrelvir-ritonavir has emergency use approval in China but is not yet approved for use in other countries. (See "COVID-19: Management of adults with acute illness in the outpatient setting", section on 'Therapies of limited or uncertain benefit'.)

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

HIV infection is associated with an excess risk of cardiovascular disease. A randomized trial evaluated the efficacy of lipid-lowering therapy with pitavastatin for primary prevention in over 7700 persons with HIV ≥40 years of age receiving antiretroviral therapy who had a 10-year atherosclerotic cardiovascular disease (ASCVD) risk score <15 percent [42]. Pitavastatin reduced the relative risk of major cardiovascular events (eg, myocardial infarction, stroke) by 35 percent compared with placebo; the trial was stopped early for this apparent benefit. Based on these data, we now advise statins in all persons ≥40 years of age with an ASCVD score ≥5 percent; for those with lower baseline risk, we also discuss statin use, although the absolute benefit is smaller. For persons younger than 40 and older than 75 years of age, our approach is the same as in persons without HIV. (See "Management of cardiovascular risk (including dyslipidemia) in patients with HIV", section on 'Indications for statins'.)

PRIMARY CARE NEPHROLOGY AND HYPERTENSION

Drug therapy to prevent recurrent urinary stone disease (May 2024)

In patients with kidney stones, drug therapy to reduce stone recurrence is indicated if the stone disease remains active or there is insufficient improvement in urine chemistries despite dietary modification; however, evidence for its effectiveness is limited. In a study of over 5600 adults with urinary stone disease and at least one urinary abnormality (hypercalciuria, hypocitraturia, or hyperuricosuria), drug therapy (thiazide diuretics, alkali therapy, or uric acid-lowering medications) was associated with a 19 percent lower risk of clinically significant recurrent stone disease over 12 to 36 months compared with no treatment [43]. This benefit did not reach statistical significance over longer follow-up periods; however, important factors that could potentially affect treatment efficacy (eg, use of appropriate drug doses, treatment adherence) were not reported. For patients with recurrent calcium oxalate stones, we tailor drug therapy based upon the presence of specific metabolic abnormalities. (See "Kidney stones in adults: Prevention of recurrent kidney stones", section on 'Drug therapy for specific metabolic abnormalities'.)

Plant-based diets and clinical outcomes in nondialysis CKD (April 2024)

Few studies have examined the association between dietary patterns and outcomes in patients with chronic kidney disease (CKD). In a prospective cohort study that included over 2500 individuals with nondialysis CKD followed for a median of 12 years, study participants with the highest adherence to overall plant-based diets and to healthy plant-based diets had a 26 and 21 percent lower risk of mortality, respectively, compared with those with the lowest adherence [44]. However, an unhealthy plant-based diet (characterized by high intakes of fruit juices, refined grains, sweets, and desserts) was associated with modestly increased risks of mortality and CKD progression. These data suggest that most patients with nondialysis CKD should consume a diet rich in fruits, vegetables, nuts, legumes, and whole grains. (See "Dietary recommendations for patients with nondialysis chronic kidney disease", section on 'Overview'.)

PRIMARY CARE NEUROLOGY

Risk of epilepsy after aneurysmal subarachnoid hemorrhage (May 2024)

Epilepsy is a known sequelae of aneurysmal subarachnoid hemorrhage (SAH), but risk factors are poorly understood. In a retrospective analysis of 419 patients with SAH who were followed for a median of 4.2 years, epilepsy was diagnosed in 12 percent at a median of seven months after SAH [45]. Incidence was modified by several variables: premorbid functional impairment, SAH-associated cerebral ischemia, surgical treatment of the aneurysm, and early-onset seizures. A predictive model for the risk of epilepsy was developed using these data, with predicted risk ranging from 3 to 76 percent depending on the score. These results may provide insight into the individual risk of epilepsy after SAH. (See "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis", section on 'Epilepsy'.)

Calcitonin gene-related peptide antagonists as a first-line preventive therapy for migraine (April 2024)

Several calcitonin gene-related peptide (CGRP) antagonists available for migraine prevention have frequently been reserved for patients with an inadequate response to initial therapy. However, in a position statement by the American Headache Society, CGRP antagonists are now considered among first-line therapies for migraine prevention, based on cumulative evidence of efficacy, safety, and tolerability from several clinical trials, meta-analyses, and postapproval open-label cohort studies [46]. They may be effective for patients with severe symptoms or frequent migraines and may provide earlier benefit than other preventive agents, and the formulations given by injection may also be helpful for those who have difficulty with daily dosing. However, cost or insurance approval may limit access to these agents as first-line therapy for some patients. (See "Preventive treatment of episodic migraine in adults", section on 'Choosing pharmacologic therapy'.)

Cerebral amyloid angiopathy as a risk for isolated subdural hematoma (February 2024)

Cerebral amyloid angiopathy (CAA) commonly presents with acute intracerebral hemorrhage that may extend into the subarachnoid or subdural spaces in some instances, but the risk of isolated spontaneous subdural hematoma (SDH) from CAA is uncertain. In a retrospective study of data from two large population-based cohorts, CAA was associated with an elevated risk of SDH after adjustment for patient demographics, cardiovascular risks, and antithrombotic medication use [47]. Leptomeningeal amyloid deposition may predispose such patients to spontaneous SDH. These results expand our understanding of the varied hemorrhagic presentations associated with CAA. (See "Cerebral amyloid angiopathy", section on 'Imaging features'.)

Time window to start dual antiplatelet therapy for high-risk TIA or minor ischemic stroke (January 2024)

There is evidence from several randomized trials that early initiation of short-term dual antiplatelet therapy (DAPT) for select patients with high-risk transient ischemic attack (TIA) or minor ischemic stroke reduces the risk of recurrent ischemic stroke. The evidence comes from trials that started DAPT within 12 to 24 hours of symptom onset. Results from the recent INSPIRES trial suggest that DAPT is still beneficial when started up to 72 hours after symptom onset [48]. Although the time window is extended by the results from INSPIRES, we start DAPT as soon as possible for patients with high-risk TIA or minor ischemic stroke. (See "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack", section on 'High-risk TIA and minor ischemic stroke'.)

Botulinum toxin injections for essential head tremor (November 2023)

Botulinum toxin (BoNT) injections have been used for refractory head tremor in patients with essential tremor (ET) based on limited data. In a randomized trial of 117 patients with essential or isolated head tremor, BoNT type A injections into each splenius capitis muscle improved subjective and objective head tremor severity measurements compared with placebo injections, with expected waning of response by 12 weeks after each injection [49]. Adverse effects were more frequent with BoNT (47 versus 16 percent), most commonly headache or neck pain, dysphagia, and posterior neck weakness. BoNT type A injections are an option for patients with bothersome head tremor due to ET who do not tolerate oral medications or whose tremor does not respond, but side effects are common and may outweigh potential benefits in some patients. (See "Essential tremor: Treatment and prognosis", section on 'Administration and efficacy'.)

Early use of ubrogepant to abort migraine headache (November 2023)

Acute migraine treatments, including calcitonin gene-related peptide (CGRP) antagonists, are typically given at headache onset, but the benefit of earlier dosing is uncertain. In a trial of 477 patients with migraine who were treated at the onset of prodromal symptoms (prior to headache), ubrongepant improved the proportion of patients who remained free of moderate to severe headache at 24 hours compared with placebo (46 versus 29 percent) [50]. Enrolled patients had migraines that consisted of prodromal symptoms (eg, photophobia, fatigue, neck pain) occurring one to six hours before headache onset in at least 75 percent of attacks. These results support our practice to administer acute migraine treatments, such as ubrogepant, early in the course of migraine symptoms. (See "Acute treatment of migraine in adults", section on 'CGRP antagonists'.)

PRIMARY CARE ORTHOPEDICS AND SPORTS MEDICINE

Running injuries in high school and collegiate athletes (March 2024)

Although running is the most common form of exercise, few high-quality reviews of running-related injuries have been published. A recent systematic review that included 24 prospective cohort studies (nearly 2000 adolescent and young adult competitive runners) found that female runners sustained more injuries than their male counterparts [51]. All runners, but particularly females, with risk factors for relative energy deficiency in sport (REDS) experienced higher injury rates; athletes with weak hip and thigh muscles were at increased risk of developing anterior knee pain (eg, patellofemoral pain). This study also confirmed known risk factors, such as a history of prior running-related injury. Overall, study quality and certainty of evidence were low to moderate. These findings reinforce the importance of sound nutrition and adjunct strength training to prevent running injuries. (See "Running injuries of the lower extremities: Risk factors and prevention", section on 'Sex and age'.)

Barbotage procedure for calcific tendinopathy of shoulder (January 2024)

To date, few high-quality studies have assessed the effectiveness of barbotage, an ultrasound-guided procedure to remove deposits in patients with calcific tendinopathy of the shoulder. In a recent, multicenter trial, 220 adults with calcific tendinopathy of at least three months duration were randomly assigned to one of three treatment arms: barbotage plus injection with glucocorticoid and analgesic; sham barbotage plus injection with glucocorticoid and analgesic; or, sham barbotage plus injection of analgesic alone [52]. At four months, patients in all three groups experienced moderate improvement in shoulder symptoms and function, but no significant differences were noted among treatment groups. At 24 months, neither barbotage with glucocorticoid injection nor glucocorticoid injection alone was superior to sham treatment (ie, analgesic injection alone). While barbotage is likely less effective than previously thought, we believe it remains a useful therapy for some patients. (See "Calcific tendinopathy of the shoulder", section on 'Barbotage'.)

PRIMARY CARE PULMONOLOGY

Vibratory devices for supine-predominant obstructive sleep apnea (April 2024)

The efficacy of chest or neck vibratory alarm devices as therapy for patients who primarily develop obstructive sleep apnea (OSA) in the supine position is poorly studied. Recently, a randomized trial of 66 such patients reported that using a vibratory device for six to eight weeks reduced sleepiness by a similar degree to continuous positive airway pressure (CPAP) therapy (-1.9 versus -2.4 points on the Epworth Sleepiness Scale score) [53]. However, despite greater adherence to the vibratory device, CPAP resulted in a greater reduction in the apnea hypopnea index. While vibratory devices restrict supine sleep, they should not be relied upon as the sole therapy for OSA but may be useful as a supplement to CPAP. (See "Obstructive sleep apnea: Overview of management in adults", section on 'Nonsupine sleep position'.)

PRIMARY CARE PSYCHIATRY

Pharmacotherapy for ADHD and mortality risk (April 2024)

Attention deficit hyperactivity disorder (ADHD) is associated with higher mortality than in the general population; whether treatment modifies that risk is unclear. In an observational study of nearly 149,000 individuals with ADHD in Sweden (mean age 17 years), initiation of medication within three months of diagnosis was associated with lower all-cause mortality (hazard ratio [HR] 0.79) as well as lower mortality from unnatural causes (eg, suicide, unintentional injury, and accidental poisoning; HR 0.75) over the ensuing two years [54]. While the study could not control for unmeasured confounders that may have impacted mortality risk (eg, lifestyle factors, social support), these data generally lend further support for pharmacotherapy of ADHD. (See "Attention deficit hyperactivity disorder in adults: Treatment overview", section on 'Benefits of stimulant treatment'.)

Exercise for treating depression (March 2024)

Evidence supports moderate to vigorous aerobic exercise for treating depression; however, the efficacy of other types of physical activity is less clear. A recent network meta-analysis of 218 randomized trials suggests that even light to moderate physical activity can improve depression [55]. Walking or jogging, dance, yoga, strength training, and tai chi significantly reduced depressive symptoms compared with active controls, and the magnitude of the effects was similar to those with standard treatments (ie, cognitive behavioral therapy or antidepressant treatment). Although the quality of evidence from most trials was low, these results support specific activity options for patients with depression who cannot engage in aerobic exercise. (See "Major depressive disorder in adults: Treatment with supplemental interventions", section on 'Type, intensity, and frequency'.)

PRIMARY CARE RHEUMATOLOGY

Adverse effects of low-dose glucocorticoids in patients with systemic lupus erythematosus (April 2024)

Glucocorticoids (GCs) are frequently required for disease control in patients with systemic lupus erythematosus (SLE) but can cause multiple adverse effects; whether low doses of GCs offer a more acceptable balance of risks and benefits is uncertain. In a national cohort study in Sweden that followed over 5300 adults with SLE for up to 15 years, compared with patients not taking oral GCs, those taking GCs had higher rates of multiple adverse outcomes, including overall mortality, various bacterial and viral infections, gastroduodenal ulcers, hypertension, osteoporosis, osteonecrosis, and cataracts [56]. Patients taking low-dose GCs (<5 mg/day) had relatively lower risks for adverse effects compared with those taking higher doses, but still had higher risks compared with patients who were not taking GCs. These results underscore the importance of using the lowest GC dose possible to control SLE activity and monitoring for adverse effects, even in patients taking low doses. (See "Systemic lupus erythematosus in adults: Overview of the management and prognosis", section on 'Prognosis'.)

Investigational use of denosumab for erosive hand osteoarthritis (April 2024)

There are limited treatment options for erosive osteoarthritis (OA) of the hand. Denosumab, a RANK ligand inhibitor used for the treatment of osteoporosis, appears promising. In a randomized trial of 100 patients with erosive hand OA, denosumab reduced radiographic progression and new erosive joint development at 48 weeks compared with placebo [57]. Pain and disability scores improved from baseline with denosumab during the open-label extension at 96 weeks, but not at earlier time points. This is the first study to demonstrate that targeted therapy can reduce structural damage in erosive hand OA, but further data on patient-important outcomes are necessary to clarify its potential role. (See "Management of hand osteoarthritis", section on 'Therapies with limited efficacy or of uncertain benefit'.)

Ultrasound for the diagnosis of giant cell arteritis (April 2024)

Vascular ultrasound is being investigated as a substitute for biopsy for the diagnosis of giant cell arteritis (GCA). In a prospective cohort study including 229 patients with suspected GCA, a prediction model using both a clinical prediction algorithm and a quantitative ultrasound was able to classify 74 percent of patients as having either a low or high probability for GCA [58]. The prediction model misclassified 2 percent of patients as low probability who eventually were diagnosed as having GCA; an additional 3 percent of patients classified as high probability for GCA were eventually reclassified as having other diagnoses. Although this study suggests that temporal artery biopsy may not be necessary to evaluate all patients with suspected GCA, it was conducted by rheumatologists who were specifically trained to use ultrasound for GCA. Until such expertise is more broadly available, we continue to evaluate patients with suspected GCA with temporal artery biopsies. (See "Diagnosis of giant cell arteritis", section on 'Patients with a positive biopsy or imaging'.)

Extra-articular rheumatoid arthritis and mortality (March 2024)

Rheumatoid arthritis (RA) is a systemic inflammatory disease that can have extra-articular manifestations, which may be severe (eg, rheumatoid vasculitis) or nonsevere (eg, rheumatoid nodules). In a study that examined outcomes of 296 patients diagnosed with RA from 1985 to 1999 and 611 patients diagnosed from 2000 to 2014, extra-articular manifestations were associated with an increased risk of mortality among all patients (hazard ratio 3.0 for severe and 1.8 for nonsevere manifestations) [59]. However, the 10-year cumulative incidence of extra-articular RA declined between the two cohorts (45 versus 32 percent). Despite the declining incidence of extra-articular RA, the presence of any extra-articular features continues to be associated with a poor prognosis. (See "Disease outcome and functional capacity in rheumatoid arthritis", section on 'Risk factors for premature mortality'.)

Diagnosis of axial spondyloarthritis using nonsteroidal anti-inflammatory agents (March 2024)

There is a long-standing belief that a dramatic response to nonsteroidal anti-inflammatory agents (NSAIDs) differentiates axial spondyloarthritis (axSpA) from other causes of lower back pain. However, in a recent prospective study of 68 consecutive patients with axSpA and 165 patients with chronic back pain from other causes who were treated with NSAIDs for four weeks, patients with axSpA were only modestly more likely to report at least 50 percent improvement in back pain (23 versus 16 percent), and the difference was not statistically significant [60]. Although this result casts some doubt on the diagnostic utility of an NSAID trial, the study was small and nonrandomized, and it does not exclude the possibility that some NSAIDs may be better than others at distinguishing axSpA from other diagnoses. (See "Diagnosis and differential diagnosis of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'History'.)

Plain radiographs in the initial evaluation of rheumatoid arthritis (March 2024)

Patients suspected of having rheumatoid arthritis (RA) are routinely evaluated with plain radiographs of the hands and feet. However, whether this is an effective strategy has not been well established. In a study of 724 patients suspected of having RA, erosions were found in only 32 patients (4.4 percent), and radiographs led to a change in disease classification for only 2 patients (0.3 percent) [61]. Patients who lacked RA-associated autoantibodies and/or acute phase reactant elevation were less likely to demonstrate RA-associated erosions. Although the yield for these outcomes was low, plain radiographs may be useful for establishing alternate diagnoses that can mimic RA (eg, pseudogout) and can identify other findings associated with RA that guide management (eg, periarticular osteopenia). (See "Diagnosis and differential diagnosis of rheumatoid arthritis", section on 'Radiologic studies'.)

Phosphodiesterase type 5 inhibition for Raynaud phenomenon (January 2024)

Phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil and tadalafil are widely used to treat digital ischemia from Raynaud phenomenon. In an updated meta-analysis of nine randomized trials comprising 411 patients with Raynaud phenomenon (most of whom had scleroderma), treatment with PDE5 inhibition resulted in three fewer attacks weekly and a reduction in the average duration of the attacks by five minutes [62]. However, PDE5 inhibition led to minimal to no reduction in the pain associated with Raynaud phenomenon. This study implies that while PDE5 inhibition has a modest impact on the duration and frequency of Raynaud attacks, it might not be adequate to address all symptoms experienced by patients with severe disease. (See "Treatment of Raynaud phenomenon: Initial management", section on 'Phosphodiesterase type 5 inhibitor'.)

Triglycerides and cardiovascular risk in rheumatoid arthritis (January 2024)

Triglycerides may be particularly important to the pathogenesis of cardiovascular disease among patients with rheumatoid arthritis (RA). In a nationwide, population-based cohort study of >15,000 statin-naïve patients with RA in Korea, the risk of major adverse cardiovascular events was higher among patients with the highest baseline triglyceride levels (≥149 mg/dL) compared with those with the lowest triglyceride levels (≤72 mg/dL; adjusted hazard ratio 1.7) [63]. The same relationship was not seen with low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or total cholesterol. This study implies that careful management of triglycerides may be particularly important to prevent cardiac events among patients with RA. (See "Coronary artery disease in rheumatoid arthritis: Pathogenesis, risk factors, clinical manifestations, and diagnostic implications", section on 'Risk factors specific to rheumatoid arthritis'.)

OTHER ADULT PRIMARY CARE

Mortality in older persons after short-term weather disasters (April 2024)

Severe weather events damage infrastructure and disrupt society, leading to direct and indirect impacts on health that can disproportionately affect vulnerable populations, including older adults. In an analysis of 42 short-term weather disasters in the United States between 2011 and 2016, emergency department utilization and mortality were higher among traditional fee-for-service Medicare beneficiaries in affected counties compared with matched control counties in the week following the disaster [64]. Higher rates of mortality persisted for six weeks and translated to an estimated 20 to 31 excess deaths per storm in the post-disaster week. Targeted solutions to minimize disruptions to health care delivery may help reduce adverse health impacts of weather events in older persons and other vulnerable populations. (See "Climate emergencies", section on 'Hurricane and flood risks to health'.)

High-dose glucocorticoid therapy not preferred in patients with sudden sensorineural hearing loss (January 2024)

Glucocorticoid therapy is the initial treatment for patients with sudden sensorineural hearing loss (SSNHL), but optimal dosing is uncertain. In a trial among 325 patients with SSNHL, five days of either high-dose intravenous prednisolone (250 mg/d) or high-dose oral dexamethasone (40 mg/d) did not improve hearing more than low-dose oral prednisone (five days at 60 mg/d followed by five days of tapering doses), but increased adverse events [65]. In patients with SSNHL, we use a low-dose regimen of oral glucocorticoids. (See "Sudden sensorineural hearing loss in adults: Evaluation and management", section on 'Initial therapy'.)