Humans

Intranasal Treatments for Children With Sleep-Disordered Breathing: The MIST+ Randomized Clinical Trial

Author/s: 
Gillian M. Nixon, Deborah Anderson, Alice Baker

Importance: Symptoms of obstructive sleep apnea are common in childhood and associated with significant comorbidity. Surgical treatment with adenotonsillectomy is first-line treatment but medical treatments show potential to improve symptoms and reduce the need for surgery.

Objective: To determine the efficacy of 6 weeks of intranasal steroid (INS) compared with saline in children with obstructive sleep-disordered breathing (OSDB) with persistent symptoms after a 6-week intranasal saline run-in.

Design, setting, and participants: This was a double-blind, placebo-controlled, randomized clinical trial involving specialist clinic waitlists at 2 sites in Australia. Included were children aged 3 to 12 years. Study data were analyzed from January to June 2025.

Interventions: All children received once-daily intranasal saline for 6 weeks (run-in). Those with persisting symptoms (SDB score ≥-1) were randomized to either once-daily intranasal mometasone furoate, 50 µg, (INS) or continued saline for a further 6 weeks.

Main outcomes and measures: The primary outcome was symptom resolution (SDB score <-1). Secondary outcomes included behavior, quality of life, and parental perception of need for surgery. Analyses were adjusted for site and baseline measures.

Results: A total of 150 children (mean [SD] age, 6.2 [2.3] years; 93 male [62%]) were recruited. Of 139 children who completed the run-in phase, 41 (29.5%) had symptom resolution after saline run-in. Among 93 children randomized to intervention groups (47 INS; 46 saline), symptom resolution occurred in 35.6% (95% CI, 22.9%-50.6%) and 36.4% (95% CI, 23.5%-51.6%) of the INS and saline group, respectively, with no evidence for a clinically significant difference between groups (risk difference, -0.9%; 95% CI, -20.7% to 19.0%; P = .93). No group differences were found in secondary outcomes. Subgroup analysis did not reveal a group more or less likely to respond to medical treatment.

Conclusions and relevance: Results of this randomized clinical trial show that 6 weeks of intranasal saline resolved OSDB symptoms in nearly one-third of children. An additional 6-week course of INS or saline led to resolution in another one-third (total resolution around 50%), with no added benefit from INS. Intranasal saline is an effective short-term first-line treatment for OSDB before consideration of polysomnography or surgical intervention. Results suggest that saline should be recommended for 3 months before assessing the need for specialist referral.

Trial registration: ClinicalTrials.gov Identifier: NCT05382494.

What Is Prostatitis?

Author/s: 
Rebecca Voelker

Prostatitis involves infection, inflammation, or pain in the prostate gland and affects about 9% of men during their lifetime.

What Is Acute Bacterial Prostatitis?
Acute bacterial prostatitis is a urinary tract infection that involves the prostate.1 Patients with acute prostatitis typically have fever, chills, pelvic pain, sudden onset of frequent urination, and pain or burning during urination. Some patients cannot empty their bladder adequately (urinary retention).

Risk factors include medical procedures such as cystoscopy, urethral catheterization, prostate biopsy, urinary obstruction such as benign prostatic hyperplasia and strictures, anal intercourse without condom use, immunosuppression, and certain neurological disorders such as multiple sclerosis, stroke, and spinal cord injury. Digital rectal examination often reveals prostate swelling and tenderness. The diagnosis of acute bacterial prostatitis is made based on symptoms, urinalysis, and urine culture. First-line treatment is 2 to 4 weeks of antibiotics. Men with urinary retention due to a swollen prostate should have a urinary catheter placed to relieve discomfort and to drain the infected urine.

What Is Chronic Bacterial Prostatitis?
Chronic bacterial prostatitis is a persistent bacterial infection of the prostate despite antibiotic therapy. Patients typically do not have fever or chills, and between episodes of infection they may have no symptoms or have persistent pelvic pain and/or lower urinary tract symptoms.

Risk factors include age 50 years or older, prior acute bacterial prostatitis, urethral surgery or catheterization, anal intercourse without condom use, and genitourinary tuberculosis. The diagnosis is made when multiple urine culture samples grow the same bacterial strain during episodes of urinary tract infection. First-line treatment for chronic bacterial prostatitis is at least 4 weeks of oral antibiotics such as ciprofloxacin or levofloxacin.

Stillbirth

Author/s: 
Adina R. Kern-Goldberger, Uma M. Reddy, Jennifer L. Bailit

Stillbirth, defined as fetal death at 20 or more weeks of gestation or 350 g or greater in birth weight, is a tragic outcome for families and clinicians.1 Stillbirth affects approximately 5.7 per 1000 births in the US—equivalent to 21 000 annually—and can occur antenatally (83%) or intrapartum (17%).2 This rate has remained relatively stable over the past 2 decades, despite substantial reductions in infant and childhood mortality.3,4 Stillbirth prevention is complex because many cases of stillbirth are unexplained, and there are substantial disparities in incidence by geographic region, socioeconomic status, and maternal race.5

Gastric Cancer: A Review

Author/s: 
Anuj Kishor Patel, Nilay S. Sethi

Importance Globally, 968 350 new cases and 659 853 deaths from gastric cancer were reported in 2022. In the US, 30 300 new cases and 10 780 deaths were estimated in 2025.

Observations Gastric cancer is more common in men, and the median age at diagnosis is 68 years. Most gastric cancers (>90%) are adenocarcinomas. Worldwide, 85% of cases arise from the stomach body or antrum and 15% from the cardia. In the US, more than 90% of patients diagnosed with gastric cancer present with symptoms such as weight loss and abdominal pain. At presentation, approximately 13% have localized disease (limited to the stomach), 15% to 25% have locally advanced disease, defined as a tumor that has spread to regional lymph nodes, and 35% to 65% have metastatic disease. Helicobacter pylori infection is a treatable risk factor associated with 90% of gastric body and antrum cancers globally. Additional modifiable risk factors include smoking, alcohol, obesity, and salt intake. In countries with high incidence such as Japan and Korea, routine endoscopic screening beginning at age 40 years is associated with improved survival. Diagnosis is made by endoscopic biopsy. Patients with localized gastric cancer are treated with surgical resection and have a 5-year relative survival rate of 75% with treatment. Patients with more advanced-stage disease should receive gastrectomy, perioperative chemotherapy with 5-fluorouracil, oxaliplatin, and docetaxel and immunotherapy (durvalumab). Metastatic or unresectable disease may be treated with chemotherapy, immunotherapy, and/or targeted therapy depending on biomarkers, including programmed cell death ligand 1 (PD-L1), human epidermal growth factor receptor 2 (ERBB2; formerly HER2 or HER2/neu), and claudin-18, isoform 2 (CLDN18.2). For PD-L1–expressing gastric cancer, adding immune checkpoint inhibitors, such as nivolumab and pembrolizumab, is associated with an additional 3 months of survival when compared with chemotherapy alone. For gastric cancers overexpressing the ERBB2 or CLDN18.2 proteins, the addition of trastuzumab or zolbetuximab, respectively, is associated with an additional 3 to 4 months’ survival. Early supportive care focusing on symptom management and on nutritional and psychosocial support is associated with 3 months of survival benefit. Less than 10% of patients with metastatic gastric cancer survive more than 5 years.

Conclusions and Relevance Approximately 30 300 new cases of gastric cancer are diagnosed annually in the US. Localized gastric cancer is treated with gastrectomy, and locally advanced disease is treated with surgery and chemoimmunotherapy. For patients with unresectable or metastatic gastric cancer, chemotherapy with immune checkpoint inhibitors and targeted therapies such as trastuzumab or zolbetuximab improves survival by several months.

Online Unsupervised Tai Chi Intervention for Knee Pain and Function in People With Knee Osteoarthritis: The RETREAT Randomized Clinical Trial

Author/s: 
Shiyi Julia Zhu, Rana S. Hinman, Rachel K. Nelligan

Importance Tai chi is a type of exercise recommended for knee osteoarthritis, but access to in-person tai chi can be limited.

Objective To evaluate the effects of an unsupervised multimodal online tai chi intervention on knee pain and function for people with knee osteoarthritis.

Design, Setting, and Participants The RETREAT study was a 2-group superiority randomized clinical trial enrolling participants who met clinical criteria for knee osteoarthritis in Australian communities from August 2023 and November 2024.

Interventions Participants in the control group received access to a purpose-built website containing information about osteoarthritis and exercise benefits. Participants in the intervention group received the My Joint Tai Chi intervention comprising access to the same website plus tai chi information, a 12-week unsupervised video-based Yang-style tai chi program, and encouragement to use an app to facilitate program adherence.

Main Outcomes and Measures Changes in knee pain during walking (Numeric Rating Scale; range 0-10 with higher scores indicating greater pain) and difficulty with physical function (Western Ontario and McMaster Universities Osteoarthritis Index; range 0-68 with higher scores indicating greater dysfunction) during 12 weeks. Secondary outcomes included another knee pain measure, sport and recreation function, quality of life, physical and mental well-being, fear of movement, self-efficacy, balance confidence, positive activated affect, sleep quality, global improvement, and oral medication use.

Results Of 2106 patients screened, 178 met inclusion criteria and were randomized, 89 (mean [SD] age, 61.0 [8.7] years; 66 female [74%] and 23 [26%] male participants) to the control group and 89 (mean [SD] age, 62.1 [7.3] years; 59 [66%] female and 30 male [34%] participants) to the tai chi intervention. Of the total, 170 (96%) completed both of the primary outcomes at 12 weeks. The tai chi group reported greater improvements in knee pain (control, −1.3; tai chi, −2.7; mean difference, −1.4 [95% CI, −2.1 to −0.7] units; P < .001) and function (control, −6.9; tai chi, −12.0; mean difference, −5.6 [95% CI, −9.0 to −2.3] units; P < .001) compared to the control group. More participants in the tai chi than in the control group achieved a minimal clinically important difference in pain (73% vs 47%; risk difference, 0.3; 95% CI, 0.1 to 0.4; P < .001) and function (72% vs 52%; risk difference, 0.2; 95% CI, 0.1 to 0.3; P = .007). Between-group differences for most secondary outcomes favored tai chi, including another knee pain measure, sport and recreation function, quality of life, physical and mental well-being, global improvement, pain self-efficacy, and balance confidence. No associated serious adverse events were reported.

Conclusions and Relevance This randomized clinical trial found that this unsupervised multimodal online tai chi intervention improved knee pain and function compared with the control at 12 weeks. This free-to-access web-based intervention offers an effective, safe, accessible, and scalable option for guideline-recommended osteoarthritis exercise.

Chronic kidney disease

Author/s: 
William G. Herrington, Parminder K. Judge, Morgan E Grams, Christoph Wanner

Globally, the prevalence of chronic kidney disease is estimated to be approximately 850 million cases, with approximately 4 million individuals needing kidney replacement therapy for kidney failure. By 2050, chronic kidney disease is projected to become the fifth leading underlying cause of death worldwide. Despite its numerous causes, chronic kidney disease can be screened for, diagnosed, and staged with simple laboratory tests. Individuals with chronic kidney disease are at increased risk of kidney failure and many other health implications. Risk of premature cardiovascular disease is particularly noteworthy, as most patients with chronic kidney disease develop a disability or die from cardiovascular disease before ever progressing to kidney failure. Since 2019, large randomised trials have identified several effective treatments that both slow progressive kidney function decline and reduce cardiovascular risk, greatly expanding available treatments for chronic kidney disease. The wide range of complications associated with chronic kidney disease means that patients encounter many different specialties. Active engagement in chronic kidney disease identification and timely initiation of cost-effective interventions by all clinicians could now substantially reduce the global burden of complications of chronic kidney disease and kidney failure.

Measles 2025

Author/s: 
Lien Anh Ha Do, Kim Mulholland

Measles is a highly contagious virus with a primary case reproduction number (i.e., the average number of secondary cases per case patient) of 12 to 18. It is currently spreading rapidly owing to reduced measles vaccination coverage, which is due primarily to the disruption of local immunization programs by the coronavirus disease 2019 (Covid-19) pandemic and of growing vaccine hesitancy.1 Since 2024, all World Health Organization (WHO) regions have reported increased numbers of measles cases, with 395,521 laboratory-confirmed measles cases reported in 2024 and 16,147 reported during the first 2 months of 2025.2 Patients in more than half the reported cases were hospitalized, so the true number is probably much higher.3
This review covers clinical presentations and complications of measles, current recommendations, and the epidemiologic background of measles. It also addresses the current debates on immunization and the treatment of measles and presents information on the origins of the various measles vaccines and updates on measles diagnostic testing and molecular genotypes.

Reducing the risk of pet-associated zoonotic infections

Author/s: 
Jason W. Stull, Jason Brophy, J.S. Weese

Pet ownership can have health, emotional and social benefits; however, pets can serve as a source of zoonotic pathogens. One large, regional survey reported more than 75% of households having contact with a pet,1 and close, intimate interactions with pets (e.g., sleeping in beds with owners, face licking) are common.1,2 Additional surveys suggest that the general public and people at high risk for pet-associated disease are not aware of the risks associated with high-risk pet practices or recommendations to reduce them; for example, 77% of households that obtained a new pet following a cancer diagnosis acquired a high-risk pet.1,3 This statistic is not surprising — studies suggest physicians do not regularly ask about pet contact, nor do they discuss the risks of zoonotic diseases with patients, regardless of the patient’s immune status.1,3,4

We review human infections acquired from pets, their risk factors and means of prevention. We limit the discussion to pet species typically owned by the general public (i.e., dogs, cats, fish, birds, amphibians, reptiles, rabbits and other rodents). Few systematic reviews or robust epidemiologic studies exist on this topic; most of our evidence comes from consensus guidelines and best practices for specific high-risk groups, with extrapolation to others

Therapeutic Use of Cannabis and Cannabinoids: A Review

Author/s: 
Michael Hsu, Arya Shah, Ayana Jordan, Mark S Gold, Kevin P Hill

Importance: Approximately 27% of adults in the US and Canada report having ever used cannabis for medical purposes. An estimated 10.5% of the US population reports using cannabidiol (CBD), a chemical compound extracted from cannabis that does not have psychoactive effects, for therapeutic purposes.

Observations: Conditions for which cannabinoids have approval from the US Food and Drug Administration include HIV/AIDS-related anorexia, chemotherapy-induced nausea and vomiting, and certain pediatric seizure disorders. A meta-analysis of randomized clinical trials reported a small but significant reduction in nausea and vomiting from various causes (eg, chemotherapy, cancer) when comparing prescribed cannabinoids (eg, dronabinol, nabilone) with placebo or active comparators (eg, alizapride, chlorpromazine; standardized mean difference [SMD], -0.29 [95% CI, -0.39 to -0.18]). A meta-analysis of randomized clinical trials among patients with HIV/AIDS reported that cannabinoids had a moderate effect on increasing body weight compared with placebo (SMD, 0.57 [95% CI, 0.22 to 0.92]). Evidence-based guidelines do not recommend the use of inhaled or high-potency cannabis (≥10% or 10 mg Δ9-tetrahydrocannabinol [Δ9-THC]) for medical purposes. High-potency cannabis compared with low-potency cannabis use is associated with increased risk of psychotic symptoms (12.4% vs 7.1%) and generalized anxiety disorder (19.1% vs 11.6%). A meta-analysis of observational studies reported that 29% of individuals who used cannabis for medical purposes met criteria for cannabis use disorder. Daily inhaled cannabis use compared with nondaily use was associated with an increased risk of coronary heart disease (2.0% vs 0.9%), myocardial infarction (1.7% vs 1.3%), and stroke (2.6% vs 1.0%). Evidence from randomized clinical trials does not support the use of cannabis or cannabinoids for most conditions for which it is promoted, such as acute pain and insomnia. Before considering cannabis or cannabinoids for medical use, clinicians should consult applicable institutional, state, and national regulations; evaluate for drug-drug interactions; and assess for contraindications (eg, pregnancy) or conditions in which risks likely outweigh benefits (eg, schizophrenia or ischemic heart disease). For patients using cannabis or cannabinoids for treatment of medical conditions, clinicians should discuss harm reduction strategies, including avoiding concurrent use with alcohol or other central nervous system depressants such as benzodiazepines, using the lowest effective dose, and avoiding use when driving or operating machinery.

Conclusions and relevance: Evidence is insufficient for the use of cannabis or cannabinoids for most medical indications. Clear guidance from clinicians is essential to support safe, evidence-based decision-making. Clinicians should weigh benefits against risks when engaging patients in informed discussions about cannabis or cannabinoid use.

Open Access Canadian guideline on HIV pre- and postexposure prophylaxis: 2025 update

Author/s: 
Darrell H.S. Tan, Mark W. Hull, Stanley O. Onyegbule, Wale Ajiboye, Camille Arkell, Jean-Guy Baril, Joseph Cox, Marianne Harris, Debbie Kelly, Michael Kwag, Gilles Lambert, Patrick O’Byrne, Shannon O’Donnell, Caley B. Shukalek, Ameeta Singh, Tatiana Sotindjo, Jaris Swidrovichv, Cécile Tremblay, Deborah Yoong

Background: New HIV infections occur annually in Canada, highlighting the need for pre- and postexposure prophylaxis (PrEP and PEP). Through the Canadian Institutes of Health Research (CIHR) Pan-Canadian Network for HIV/AIDS and STBBI (sexually transmitted and blood-borne infections) Clinical Trials Research, we have updated the 2017 guideline on clinical indications and drug regimens for PrEP and PEP in Canada.

Methods: Drawing on meetings with community-based organizations representing key populations affected by HIV in Canada, along with evidence from 3 systematic reviews on PrEP, PEP, and HIV risk assessment tools (searches to June 2024), our diverse panel of 19 experts formulated recommendations on PrEP and PEP. We used a formal evidence-to-decision-making framework and the Grading of Recommendations, Assessment, Development, and Evaluation system. We followed the Guidelines International Network principles for managing competing interests. Our guideline development and reporting adhere with Appraisal of Guidelines for Research and Evaluation II.

Recommendations: This guideline contains 31 recommendations and 10 good practice statements. Although it is appropriate to prescribe PrEP to adults and adolescents who request it, clinicians are also encouraged to assess HIV risk during routine health visits to identify people who would benefit from PrEP. Clinicians should elicit information about patients' anatomy and sexual partners in a culturally sensitive and affirming manner to determine which PrEP regimens - daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), on-demand TDF/FTC, daily oral tenofovir alafenamide/emtricitabine, or long-acting injectable cabotegravir - are suitable options. When assessing whether PEP is needed, clinicians should consider the likelihood that the source person has transmissible HIV, as well as the biological risk of HIV transmission based on exposure type. Preferred PEP regimens are dolutegravir plus TDF/FTC, or bictegravir/tenofovir alafenamide/emtricitabine.

Interpretation: Multiple safe, effective PrEP and PEP regimens are now available in Canada, making it increasingly possible to find suitable options for all who could benefit. Implementation of this guideline should expand access to biomedical HIV prevention interventions for those at risk and decrease the incidence of HIV in Canada.

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