OPHTHALMOLOGY

Clinical trials for conditions affecting the visual system need to not only conform to the guidelines for all clinical trials, but also accommodate the possibility of both eyes of a single patient qualifying for the trial. In this review, I present the interplay of the key components in the design of a clinical trial, along with the modifications or options that may be available for trials addressing ocular conditions. Examples drawn from published reports of the design and results of clinical trials of ocular conditions are provided to illustrate application of the design principles.

Designing Clinical Trials for Ocular Conditions: Key Components and Considerations for Visual System Disorders

CARDIOLOGY

Adipose miR-30e-5p may promote obesity-related atherosclerosis by disrupting SLC7A11 and endothelial function.

Adipose miR-30e-5p Linked to Obesity-Related Atherosclerosis

A multiomics study identified an adipose-derived miR-30e-5p–SLC7A11 pathway linking obesity to atherosclerosis. Carried in serum exosomes, miR-30e-5p targeted vascular endothelial cells, disrupting cystine/glutamate metabolism, mitochondrial function, and endothelial health. Blocking miR-30e-5p reduced atherosclerosis in obese and atherosclerotic mice, highlighting a potential therapeutic pathway.

Fragility analysis suggests RCT evidence for saline nasal irrigation in rhinosinusitis may be statistically fragile.

Saline Nasal Irrigation Evidence Shows Statistical Fragility

A systematic fragility analysis of 8 randomized controlled trials found that evidence for high-volume saline nasal irrigation in rhinosinusitis may be statistically fragile. Among 38 dichotomous outcomes, only 8 were significant, with a median fragility index of 5. In over one-fifth of outcomes, loss to follow-up exceeded the number of event changes needed to reverse statistical significance.

PULMONOLOGY

Greater exposure to green and natural environments was linked to lower COPD risk regardless of genetic susceptibility.

Green Space Exposure Linked to Lower COPD Risk

A prospective UK Biobank study of 385,502 adults found that greater residential exposure to green space and natural environments was associated with a lower risk of developing COPD. Natural environment exposure reduced COPD risk across genetic-risk groups, with no significant gene–environment interaction. Blue-space associations were weaker and inconsistent, supporting environmental strategies for COPD prevention.

Smoking history may be linked to poorer overall survival after TORS for HPV-associated oropharyngeal cancer.

Smoking and Survival Outcomes in HPV-Associated OPSCC

A meta-analysis of 12 studies involving 2,079 patients with HPV-associated oropharyngeal squamous cell carcinoma treated with transoral robotic surgery found no significant difference in recurrence-free or disease-specific survival by smoking history. However, patients with a smoking history appeared to have poorer overall survival, highlighting the need for further research.

Bimodal stimulation showed consistent, durable improvements in chronic tinnitus, while other neuromodulation approaches had variable benefits.

Bimodal Stimulation Shows Promise for Chronic Tinnitus

A systematic review and meta-analysis of 26 randomized controlled trials involving 1,576 adults found that noninvasive neuromodulation for chronic subjective tinnitus was generally safe but offered variable benefits. Bimodal stimulation showed the most consistent and durable improvements, with tinnitus severity reductions often reaching 10–20 points on validated scales and benefits lasting up to 12 months.

Ambient AI scribes may improve documentation efficiency and reduce burnout, but evidence in otolaryngology remains limited.

Ambient AI Scribes Improve Documentation and Reduce Burnout

A scoping review of 12 studies found that ambient AI scribing may improve clinical documentation and workflow while reducing clinician burnout. Time saved per note ranged from 0.2 to 2.1 minutes, with after-hours documentation reduced by up to 15.2 minutes. However, evidence specific to otolaryngology remains limited, particularly for patients with communication challenges.

Nasolabial flaps offer reliable reconstruction for selected oral cancer defects, with low complication and donor-site morbidity rates.

Nasolabial Flap Effective for Oral Cancer Reconstruction

A systematic review and meta-analysis of 25 studies involving 827 patients found that nasolabial flap reconstruction is a reliable option for selected small- to medium-sized oral cavity defects following cancer surgery. Pooled flap necrosis was 3.4%, overall complications 9.2%, and donor-site morbidity 0.9%, with generally favorable functional and aesthetic outcomes.

Severe aortic stenosis with mitral regurgitation was linked to higher mortality, while TAVR improved MR in most patients.

Aortic Stenosis With Mitral Regurgitation: Mortality and TAVR Outcomes

A large US analysis of 36,402 patients with severe aortic stenosis and moderate or greater mitral regurgitation found substantially higher 2-year mortality with increasing MR severity. Despite this risk, 52% remained untreated. Among patients undergoing TAVR alone, 77.5% experienced improvement in MR, highlighting the potential benefit of addressing aortic valve disease.

CRITICAL CARE

Hypoxic hepatitis may signal severe systemic illness and poorer survival in critically ill patients

Hypoxic Hepatitis Linked to Poorer Survival in Critical Illness

A systematic review and meta-analysis of five cohort studies involving 107,346 critically ill patients found that hypoxic hepatitis was associated with markers of severe illness and poorer survival. Mechanical ventilation and vasopressor support were linked to lower survival, while lactate, bilirubin, and INR did not predict outcomes, suggesting HH reflects underlying systemic failure more than an independent cause of mortality.

NSAIDs improved pain control and reduced opioid use after TORS without significantly increasing postoperative hemorrhage risk.

NSAIDs Reduce Pain and Opioid Use After TORS Without Higher Bleeding Risk

A meta-analysis of 8 studies involving 2,519 patients found that NSAID-containing regimens after transoral robotic surgery reduced pain within 72 hours, inpatient opioid use, and discharge opioid prescribing. Although postoperative hemorrhage occurred in 8.31% of NSAID-treated patients, NSAIDs did not significantly increase hemorrhage risk, supporting their use in postoperative pain protocols.

NEUROLOGY

SynthPET uses MRI and AI to generate FDG PET images, potentially improving access to metabolic imaging in Alzheimer’s disease.

AI Framework Generates FDG PET Images From MRI for Alzheimer’s

Researchers developed SynthPET, a deep learning framework that generates FDG PET images from routinely acquired T1-weighted and arterial spin labeling MRI. Both models showed high similarity to real PET images, with strong diagnostic performance in Alzheimer’s disease regions. The approach could expand access to metabolic brain imaging while reducing PET-related cost and radiation exposure.

DENTISTRY

Inflammasome activation may mark the transition to irreversible pulpitis and help refine vital pulp therapy decisions.

Inflammasome Activation May Define Irreversible Pulpitis

A structured narrative review proposes that inflammasome activation may mark the biological transition from reversible to irreversible pulpitis. Evidence indicates that ASC speck formation triggers caspase-1 activation, gasdermin D-mediated pyroptosis, and IL-1β/IL-18 signalling, creating self-amplifying inflammation and tissue breakdown. The model could refine diagnosis and help redefine the biological limits of vital pulp therapy.

Cyclosporine 0.09% and 0.1% ranked highest for corneal healing in moderate-to-severe dry eye disease.

Cyclosporine and Tacrolimus Compared for Moderate-to-Severe Dry Eye

A systematic review and Bayesian network meta-analysis of 29 RCTs involving 8,453 patients compared topical cyclosporine, tacrolimus, and neurostimulatory nasal sprays for moderate-to-severe dry eye disease. Cyclosporine 0.09% and 0.1% ranked highest for corneal staining improvement, while tacrolimus showed early improvements in tear production and stability. Varenicline increased tear production but needs further comparative validation.

Central retinal vein occlusion was the leading cause of neovascular glaucoma, with visual outcomes strongly dependent on aetiology.

Central Retinal Vein Occlusion Leads Causes of Neovascular Glaucoma

A longitudinal study of 626 patients with neovascular glaucoma followed for a median of 24 months found central retinal vein occlusion was the leading cause (45%), followed by diabetic retinopathy (14%) and central retinal artery occlusion (11%). Baseline vision was often severely impaired, while IOP fell from 40 to 20 mmHg at 1 year and ocular pain declined substantially. Visual prognosis varied significantly by underlying cause.

Reciproc Minima M25 showed high fatigue resistance and flexibility with lower dentinal stress during simulated canal preparation.

Reciproc Minima Shows High Fatigue Resistance in NiTi Instruments

A comparative study of 441 NiTi instruments from seven reciprocating systems found significant differences in geometry and mechanical performance. Reciproc Minima M25 had the highest cyclic fatigue resistance, greater flexibility, and high torsional performance, while its reduced taper and smaller blade volume were associated with lower dentinal stress. Reciproc R25 showed the greatest torsional and buckling resistance.

Best Practices for the De...

Best Practices for the Design of Clinical Trials Related to the Visual System