Tobacco use is the leading cause of preventable death globally, claiming more than 7 million lives each year. The burden of disease is highest in low- and middle-income countries, where more than 80% of the world's 1.3 billion tobacco users reside. The World Health Organization (WHO) defines six proven strategies to reduce tobacco use, referred to by the acronym MPOWER, with one of the strategies being to offer tobacco users help with quitting. Many low- and middle-income countries provide tobacco-cessation services; however, only 31 meet the WHO best practice, defined as providing both cost-covered behavioral interventions and pharmacotherapy. In this article, case studies from India and Vietnam illustrate how cross-country differences in tobacco-related sociocultural norms, tobacco-use patterns (e.g., smokeless tobacco or water pipes), the tobacco-control regulatory environment, industry influence, and health care system financing shape treatment access and uptake. These cases further show that cost-effective population-level strategies, including quitlines, digital interventions, and systemwide screening for tobacco use paired with clinician advice to quit, are essential for expanding treatment reach. Combining these interventions with pharmacotherapy products that are included on the WHO Model List of Essential Medicines (e.g., cytisine and nicotine-replacement therapy) further improves cessation outcomes. System-level models, such as the Ask-Advise-Connect model (ask about tobacco use, advise to quit, connect to cessation help), offer a feasible, low-burden pathway for integrating cessation care into routine practice. Ultimately, curbing the rising global burden of tobacco-related disease requires establishing comprehensive cessation support as a universal standard of care, which would ensure equitable access for those most affected.

Syncope is a common clinical problem caused by transient cerebral hypoperfusion and encompasses reflex, orthostatic, and cardiac mechanisms. Accurate diagnosis relies on careful history taking and physical examination, as well as targeted testing guided by risk stratification. Management of syncope is determined on the basis of the underlying mechanism and focuses on reducing recurrence and injury risk. In older patients, syncope may manifest as unexplained falls. Early identification of high-risk features is critical to prevent adverse cardiovascular outcomes.

Nav1.8, a voltage-gated sodium channel expressed in the peripheral nervous system, has a critical role in pain signaling. Previous trials of NaV1.8 inhibitors have shown effectiveness in reducing postoperative pain.

Once-daily, single-tablet regimens have transformed care for persons living with human immunodeficiency virus type 1 (HIV-1); however, challenges to adherence continue to limit effective treatment. Long-acting oral-drug combinations could offer new options with less frequent dose administration.

The development of effective treatment strategies for human immunodeficiency virus (HIV) infection is a major achievement. Antiretroviral drugs inhibit key steps in the viral replication cycle and consist of six mechanistic classes: HIV entry inhibitors, reverse-transcriptase inhibitors (both nucleosides and nonnucleosides), capsid inhibitors, integrase inhibitors, and protease inhibitors. Antiretroviral therapy (ART) suppresses viral replication, thereby enhancing immune function, decreasing morbidity and mortality, and preventing viral transmission. Consequently, ART is recommended for all persons with HIV infection. On the basis of randomized clinical trials, the Food and Drug Administration has approved 36 antiretroviral drugs for the treatment of HIV infection since 1987; of these, 28 are currently available in the United States, and combination ART regimens are used. Initial preferred ART regimens are potent, convenient, and unlikely to cause side effects and consist of an HIV integrase inhibitor with a high barrier to resistance combined with one or two nucleoside reverse-transcriptase inhibitors. In the majority of patients using current ART regimens, viral replication is durably suppressed below detectable levels. Patients receiving ART are monitored for virologic response over time, and if virologic failure occurs, the next regimen is selected on the basis of treatment history and the results of drug-resistance testing; often, antiretroviral drugs from new classes are administered. Today, the life expectancy of someone with HIV infection who consistently takes ART approaches that of the general population.

Neoadjuvant cisplatin-based chemotherapy is a standard therapy for muscle-invasive bladder cancer. The efficacy and safety of neoadjuvant and adjuvant (perioperative) enfortumab vedotin-pembrolizumab as compared with neoadjuvant cisplatin-based chemotherapy in persons with this cancer are unclear.

Fibromyalgia is characterized by widespread pain involving any body tissue and typically accompanied by fatigue and problems with sleep, mood, and memory. Fibromyalgia can occur alone or in combination with other chronic overlapping primary pain conditions, or it can be superimposed on other conditions, such as autoimmune disorders (secondary pain). In fibromyalgia, the central nervous system (CNS) is hyperresponsive to sensory stimuli generally. Successful pharmacologic and nonpharmacologic interventions focus on the CNS to support CNS quiescence and a return to homeostasis. Although fibromyalgia is rarely curable, most cases can be well managed in the context of primary care.

Prevalence surveys in U.S. hospitals showed that on any given day, 1 of 25 patients had a health care-associated infection in 2011, as compared with 1 of 31 patients in 2015. We repeated the survey in 2023 to assess changes in the prevalence of such infections.

Patients with multivessel coronary artery disease often receive 12 months of dual antiplatelet therapy (DAPT) after stenting to reduce the risk of ischemic events. Whether extending DAPT beyond 12 months in event-free patients with multivessel disease provides a benefit is uncertain.

Current treatment of newly diagnosed multiple myeloma involves lenalidomide maintenance therapy given until disease progression. The appropriate duration of maintenance therapy with lenalidomide has been unclear.

Andes virus (ANDV) is the sole orthohantavirus with documented human-to-human transmission. We summarize the epidemiology and clinical features of ANDV infection and review best practices in clinical management, as based on published expert consensus guidelines, field experience, and clinical trials. We also evaluate currently available and investigational treatments (including the use of antiviral agents), assess emerging monoclonal antibody therapies, and outline prospects for vaccine development. Finally, we discuss important infection prevention and control measures.

Platelet-activating antibodies against platelet factor 4 (PF4) cause highly prothrombotic disorders with reduced platelet counts. In heparin-induced thrombocytopenia (HIT), these antibodies bind PF4-heparin complexes, causing heparin-dependent platelet activation. Less common autoimmune and spontaneous HIT variants that are triggered by heparin and nonpharmacologic polyanions, respectively, have atypical clinical features and antibodies with additional heparin-independent platelet-activating properties. Vaccine-induced immune thrombocytopenia and thrombosis (VITT) antibodies directly target PF4. Initially, VITT was linked to adenoviral vector-based coronavirus disease 2019 vaccines, but in rare cases, an immune thrombocytopenia and thrombosis disorder that is clinically nearly identical to VITT can be caused by infection resulting from natural exposure to viruses, especially adenovirus. In persons with the IGLV3-21*02/*03 gene, anti-adenovirus protein VII antibody specificity shifts to PF4 by way of a specific somatic hypermutation (K31E) that creates VITT antibodies. In VITT-like monoclonal gammopathy of thrombotic significance, monoclonal anti-PF4 antibodies cause chronic prothrombotic conditions. Accurate diagnosis relies on distinct assays for HIT and VITT antibodies. Beyond anticoagulation, inhibition of FcγIIa receptor-mediated platelet activation may be needed for anti-PF4 disorders with heparin-independent reactivity (e.g., high-dose immune globulin in acute disease manifestations and Bruton's tyrosine kinase inhibitors in chronic manifestations).

Aspirin after an initial short course of rivaroxaban has been shown to be safe and effective for the prevention of venous thromboembolism after total hip or total knee arthroplasty, but uncertainty remains about the use of aspirin alone.

No vaccines are currently licensed for the prevention of Neisseria gonorrhoeae infection. Observational studies suggest that the four-component meningococcal serogroup B vaccine (4CMenB) may reduce the risk of gonorrhea.

In the acute phase of critical illness, adults have severe catabolism, inflammation, muscle loss, and gut dysfunction, all of which shape nutritional requirements. Early enteral nutrition supports gut integrity and microbiome health, but trials have shown that early short-term parenteral nutrition is a safe alternative when enteral feeding is not possible. Large trials have shown that early full-dose energy delivery offers no benefit over restrictive dosing and may increase gastrointestinal and metabolic complications, findings that support a restrictive nutrition strategy, especially in patients who have circulatory shock or are at risk for refeeding syndrome. Similarly, large trials have shown no advantage of high-dose over standard-dose protein and suggest harm in patients with acute kidney injury. Because adverse events are common with enteral nutrition, safe nutrition delivery requires gradual advancement, strategies for prevention of refeeding syndrome, glycemic control, and avoidance of routine gastric residual volume monitoring. Patient heterogeneity underscores the need for precise, biomarker-guided, phase-specific nutrition to preserve lean muscle mass and improve recovery.

Anaplastic lymphoma kinase (ALK) inhibitors have emerged as promising agents for patients with resectable ALK-positive non-small-cell lung cancer (NSCLC). Whether ensartinib, a second-generation ALK inhibitor, is safe and effective in such patients is unknown.

A phase 2 trial of setmelanotide, a melanocortin-4 receptor agonist, showed substantial weight loss in patients with acquired hypothalamic obesity, but additional data are needed.

Multiple sclerosis is a chronic autoimmune disorder that affects the central nervous system, causing episodes of neurologic dysfunction and often gradual disease progression. The immune system primarily targets myelin, the protective covering of nerve fibers, leading to inflammation and damage, and secondary neurodegeneration is a major cause of long-term disability. Common symptoms include vision problems, sensory disturbances, muscle weakness, balance difficulties, and bladder dysfunction. Important advances in treatment have improved outcomes in patients with relapsing forms of multiple sclerosis, particularly through highly effective immune-modifying therapies such as CD20-targeting monoclonal antibodies. However, treatment options for progressive forms remain limited, which highlights the need for therapies that can prevent progression and promote myelin repair. Comprehensive symptom management and lifestyle support are also essential to maintaining quality of life and reducing disability.

Anti-CD20 monoclonal antibodies are effective for relapsing multiple sclerosis. However, data from head-to-head trials are lacking.

Adjuvant pembrolizumab improves disease-free and overall survival among patients with resected clear-cell renal-cell carcinoma. The hypoxia-inducible factor 2α inhibitor belzutifan has activity in advanced disease. Adjuvant pembrolizumab with belzutifan may further improve outcomes in patients with clear-cell renal-cell carcinoma at increased risk for recurrence.