The speed of drug regulatory agencies in the United States and Europe is often a source of discussion. The objective of this research was to assess regulatory review duration of first and supplementary indications approved between 2011 and 2020 in the United States and Europe (European Union [EU] and Switzerland) and differences in submission times between the United States and Europe. Descriptive statistics were applied to review times between the jurisdictions and across the therapeutic areas. A regression analysis was done to estimate the association between approval agency and review times. The primary analysis cohort included 241 drugs approved in the United States, the EU, and Switzerland. Of these, 128 drugs had supplemental indications (331 in total) in the United States and 87 had supplemental indications (206 in total) in the EU. Overall median review duration from submission to approval subtracting the clock stop period was 39 weeks in the United States, 44 weeks in the EU, and 44 weeks in Switzerland. When review times within each drug were compared, the European Medicines Agency took a median of 3.7 weeks (IQR, -6.7 to 14.9 weeks) longer than the U.S. Food and Drug Administration and Swissmedic a median of 0.3 weeks (IQR, -10.6 to 15.3 weeks) longer. Median total review duration for supplemental indications was 26 weeks in the United States and 40 weeks in the EU. Applications were submitted a median of 1.3 and 17.9 weeks later in the EU and Switzerland, respectively, than in the United States. The regression analysis showed small differences in submission times between the United States and the EU (-2.1 weeks [95% CI, -11.7 to 7.6 weeks]) and larger differences between the United States and Switzerland (33.0 weeks [CI, 23.1 to 42.8 weeks]). It would be beneficial for patients if differences in submission times between the United States and Europe continue to be minimized.

Substantial effort has been directed toward demonstrating uses of predictive models in health care. However, implementation of these models into clinical practice may influence patient outcomes, which in turn are captured in electronic health record data. As a result, deployed models may affect the predictive ability of current and future models.

Dementia, according to the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, is defined by a significant decline in 1 or more cognitive domains that interferes with a person's independence in daily activities. Mild cognitive impairment (MCI) differs from dementia in that the impairment is not sufficient to interfere with independence. For the purposes of this discussion, cognitive impairment (CI) includes both dementia and MCI. Various screening tests are available for CI. These tests ask patients to perform a series of tasks that assess 1 or more domains of cognitive function or ask a caregiver to report on the patient's abilities. A positive result on a screening test does not equate to a diagnosis of CI; rather, it should lead to additional testing to confirm the diagnosis. On review of the evidence, the U.S. Preventive Services Task Force (USPSTF) concluded in 2020 that the evidence was insufficient to assess the balance of benefits and harms of screening for CI in older adults ("I statement"). The USPSTF did clarify that although there is insufficient evidence, there may be important reasons to identify CI. In this article, 2 experts review the available evidence to answer the following questions: What screening tools are available, and how effective are they in identifying patients with CI? What interventions are available for patients found to have CI, to what extent do they improve patient outcomes, and what, if any, negative effects occur? And, would they recommend screening for CI, and why or why not?

Xylazine is an animal sedative, approved by the U.S. Food and Drug Administration, that is commonly used in veterinary medicine and is not approved for human use. Since 2016, xylazine has consistently appeared in the illicitly manufactured fentanyl supply and has significantly increased in prevalence, likely due to its low cost, easy availability, and presumed synergistic psychoactive effect. Clinical experience along with the available pertinent research were used to review xylazine adulteration of the drug supply and provide guidance on the care of patients exposed to xylazine. This review discusses xylazine pharmacology, animal and human clinical effects, and what is known to date about care of patients experiencing acute overdose, xylazine-fentanyl withdrawal, and xylazine-associated wounds.

More than 2 million children are conceived annually using assisted reproductive technologies (ARTs), with a similar number conceived using ovulation induction and intrauterine insemination (OI/IUI). Previous studies suggest that ART-conceived children are at increased risk for congenital anomalies (CAs). However, the role of underlying infertility in this risk remains unclear, and ART clinical and laboratory practices have changed drastically over time, particularly there has been an increase in intracytoplasmic sperm injection (ICSI) and cryopreservation.

COVID-19, the illness caused by SARS-CoV-2, became a worldwide pandemic in 2020. Initial clinical manifestations range from asymptomatic infection to mild upper respiratory illness but may progress to pulmonary involvement with hypoxemia and, in some cases, multiorgan involvement, shock, and death. Older adults, pregnant persons, those with common comorbidities, and those with immunosuppression are at greatest risk for progression. Vaccination is effective in preventing symptomatic infection and reducing risk for severe disease, hospitalization, and death. Antiviral treatment and immunomodulators have been shown to benefit certain patients. This article summarizes current recommendations on prevention, diagnosis, management, and treatment of COVID-19.

Rosenstock J, Bain SC, Gowda A, et al; ONWARDS 1 Trial Investigators. Weekly icodec versus daily glargine U100 in type 2 diabetes without previous insulin. N Engl J Med. 2023;389:297-308. 37356066.

Bronchiectasis in adults with chronic obstructive pulmonary disease (COPD) is associated with greater mortality. However, whether suspected bronchiectasis-defined as incidental bronchiectasis on computed tomography (CT) images plus clinical manifestation-is associated with increased mortality in adults with a history of smoking with normal spirometry and preserved ratio impaired spirometry (PRISm) is unknown.

Atrial fibrillation (AF) is often detected for the first time in patients who are hospitalized for another reason. Long-term risks for AF recurrence in these patients are unclear.

McQuilten ZK, Thao LT, Pasricha SR, et al. Effect of low-dose aspirin versus placebo on incidence of anemia in the elderly: a secondary analysis of the Aspirin in Reducing Events in the Elderly trial. Ann Intern Med. 2023;176:913-921. 37335992.

Planer D, Yanko S, Matok I, et al. Catheter-directed thrombolysis compared with systemic thrombolysis and anticoagulation in patients with intermediate- or high-risk pulmonary embolism: systematic review and network meta-analysis. CMAJ. 2023;195:E833-E843. 37336568.

Wharton S, Blevins T, Connery L, et al; GZGI investigators. Daily oral GLP-1 receptor agonist orforglipron for adults with obesity. N Engl J Med. 2023;389:877-880. 37351564.

Previous studies have shown that patients with giant cell arteritis (GCA) who have vascular 18F-fluorodeoxyglucose (FDG) uptake at diagnosis are at increased risk for thoracic aortic complications.

Lingvay I, Asong M, Desouza C, et al. Once-weekly insulin icodec vs once-daily insulin degludec in adults with insulin-naive type 2 diabetes: the ONWARDS 3 randomized clinical trial. JAMA. 2023;330:228-237. 37354562.

Primary osteoporosis is characterized by decreasing bone mass and density and reduced bone strength that leads to a higher risk for fracture, especially hip and spine fractures. The prevalence of osteoporosis in the United States is estimated at 12.6% for adults older than 50 years. Although it is most frequently diagnosed in White and Asian females, it still affects males and females of all ethnicities. Osteoporosis is considered a major health issue, which has prompted the development and use of several performance measures to assess and improve the effectiveness of screening, diagnosis, and treatment. These performance measures are often used in accountability, public reporting, and/or payment programs. However, the reliability, validity, evidence, attribution, and meaningfulness of performance measures have been questioned. The purpose of this paper is to present a review of current performance measures on osteoporosis and inform physicians, payers, and policymakers in their selection of performance measures for this condition. The Performance Measurement Committee identified 6 osteoporosis performance measures relevant to internal medicine physicians, only 1 of which was found valid at all levels of attribution. This paper also proposes a performance measure concept to address a performance gap for the initial approach to therapy for patients with a new diagnosis of osteoporosis based on the current American College of Physicians guideline.

Chen HS, Cui Y, Zhou ZH, et al; ARAMIS Investigators. Dual antiplatelet therapy vs alteplase for patients with minor nondisabling acute ischemic stroke: the ARAMIS randomized clinical trial. JAMA. 2023;329:2135-2144. 37367978.

Romanet C, Wormser J, Fels A, et al. Effectiveness of exercise training on the dyspnoea of individuals with long COVID: a randomised controlled multicentre trial. Ann Phys Rehabil Med. 2023;66:101765. 37271020.

Zi W, Song J, Kong W, et al; RESCUE BT2 Investigators. Tirofiban for stroke without large or medium-sized vessel occlusion. N Engl J Med. 2023;388:2025-2036. 37256974.

Rigotti NA, Benowitz NL, Prochaska J, et al. Cytisinicline for smoking cessation: a randomized clinical trial. JAMA. 2023;330:152-160. 37432430.

Fatima K, Asad D, Shaikh N, et al. A systematic review and meta-analysis on effectiveness of mineralocorticoid receptor antagonists in reducing the risk of atrial fibrillation. Am J Cardiol. 2023;199:85-91. 37269781.