The Effectiveness Of Preoperative Delirium Prevention In Intermediate To High-Risk Older Surgical Patients
Despite the promising results for fascia iliaca compartment block and methylprednisolone, there is limited knowledge regarding evidence-based delirium prevention interventions.
KEY FINDINGS: Despite the promising results for fascia iliaca compartment block and methylprednisolone, there is limited knowledge regarding evidence-based delirium prevention interventions. Most studies had small sample sizes indicating that the current evidence is exploratory. There is an urgent need for the funding and conduct of trials to test preventative interventions for older surgical patients at intermediate to high risk of developing delirium.
BACKGROUND: Few reviews have addressed delirium prevention among intermediate to high-risk older surgical patients. Purpose of this study is to map preoperative delirium prevention interventions for older surgical patients at intermediate to high risk of developing delirium, assess outcomes and identify gaps in knowledge.
DETAILS: A systematic search was conducted of the literature published from 1990 to October 2022 in Medline, CINAHL and Ageline and of the grey literature in Google Scholar. Randomised controlled trials were retrieved that assessed the effectiveness of preoperative delirium prevention interventions for older surgical patients at intermediate to high risk of delirium. Data were extracted using a data extraction tool, and results were tabulated. Studies were assessed for bias using the Cochrane Collaboration Risk of Bias tool. Twenty-one studies met the selection criteria including N = 5096 participants. Two studies tested cognitive training, two studies tested fascia iliaca compartment block and one study assessed femoral nerve block. Ten studies tested prophylactic medications including methylprednisolone. Five studies investigated geriatric assessment and management. One study assessed transcutaneous electrical acupoint stimulation. In the two studies testing fascia iliaca compartment block, there was a reduction in postoperative delirium for orthopaedic patients. Methylprednisolone reduced postoperative delirium in orthopaedic patients and in those undergoing gastrointestinal surgery. Results of all other interventions on the occurrence of postoperative delirium and additional outcomes including the severity and duration of delirium were inconclusive.
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Source: Lay, N., Foley, P., and Allen, J. (2024). The Effectiveness Of Preoperative Delirium Prevention In Intermediate To High-Risk Older Surgical Patients: A Systematic Review. J Clin Nurs. 2024; 33(5): 1666-1683. Published: May, 2024. DOI: 10.1111/jocn.17020.
Cardiovascular, Bone, and Mortality Outcomes in Older Adults
A UK emulated target trial involving 19,027 adults found that initial levothyroxine dosing above 1.0 microgram per kg per day was associated with increased long-term risks of cardiovascular events, bone outcomes, and all-cause mortality. The findings highlight the importance of cautious dose selection and individualized titration in older adults, although prospective studies are needed to confirm these associations.
KEY FINDINGS: Among adults older than 50 years initiating levothyroxine, an initial dose exceeding 1.0 μg/kg per day was associated with higher long-term risks of cardiovascular events, bone outcomes, and all-cause mortality compared with lower initial dosing. The findings support careful consideration of initial dose and subsequent titration in older patients. However, the observational design does not establish that higher dosing directly caused these outcomes, and prospective studies are needed to validate the findings.
BACKGROUND: Levothyroxine is commonly prescribed for hypothyroidism, but determining an appropriate initial dose in older adults remains challenging. Both insufficient and excessive thyroid hormone replacement may adversely affect cardiovascular health, bone integrity, and survival. This study used an emulated target trial approach to evaluate the association between initial weight-based levothyroxine dosing and long-term clinical outcomes in adults older than 50 years.
DETAILS: This observational study used data from The Health Improvement Network, a UK primary care database, covering January 1, 2006, through December 31, 2021. Eligible participants were adults older than 50 years with diagnosed hypothyroidism, at least one recorded thyroid-stimulating hormone (TSH) measurement exceeding 4.0 mU/L, and a new levothyroxine prescription during the study period. The investigators compared patients initiating levothyroxine at more than 1.0 μg/kg per day with those receiving 1.0 μg/kg per day or less. Dosing was assessed using both total bodyweight and lean bodyweight. Participants were followed for up to 10 years for cardiovascular events, bone outcomes, and all-cause mortality. Inverse probability of treatment weighting was used to adjust for baseline confounders, and weighted Cox proportional hazards models were applied to estimate outcome associations.
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A total of 19,027 records were eligible, including 14,296 women (75%) and 4,731 men (25%). The cardiovascular analysis included 15,463 adults, the bone health analysis included 14,947, and all 19,027 participants were included in the mortality analysis. Unweighted event rates were higher among patients initiating levothyroxine at more than 1.0 μg/kg per day than among those receiving lower doses. Cardiovascular events occurred in 20% versus 18%, bone outcomes in 13% versus 9%, and all-cause mortality in 18% versus 17%, respectively. Higher initial dosing was associated with increased risk of cardiovascular events (adjusted hazard ratio [HR], 1.18; 95% CI, 1.08-1.29), bone outcomes (HR, 1.29; 95% CI, 1.16-1.43), and all-cause mortality (HR, 1.17; 95% CI, 1.09-1.25).
Using total bodyweight-based dosing, the weighted 10-year absolute risk differences between the higher- and lower-dose groups were 1.3% (95% CI, 0.3-3.0) for cardiovascular events, 3.0% (95% CI, 1.6-4.5) for bone outcomes, and 3.4% (95% CI, 1.7-5.1) for all-cause mortality. Similar associations were observed in analyses using lean bodyweight-based dosing.
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Source: Holley, M., Wilkes, S., Moss, E. D., et al. Weight-based levothyroxine dosing and long-term cardiovascular, bone, and mortality outcomes in older adults: an emulated target trial using UK primary care data. The Lancet Primary Care. 2026; 2(8): 100194. Published: August, 2026. DOI: 10.1016/j.lanprc.2026.100194.
AI-Assisted Colonoscopy for Colorectal Lesion Detection in Lynch Syndrome
A multicentre randomized trial of 733 patients with Lynch syndrome found that AI-assisted colonoscopy did not significantly increase adenoma detection compared with high-definition white-light colonoscopy alone (33.8% vs 30.9%; P=0.41). AI-based lesion characterization showed good sensitivity and specificity but did not clearly improve on expert optical diagnosis in specialized surveillance settings.
KEY FINDINGS: In this international randomized trial conducted at specialized Lynch syndrome surveillance centres, adding AI-assisted detection to high-definition white-light colonoscopy did not significantly increase adenoma detection. Although the CADx system demonstrated good sensitivity and specificity for lesion differentiation, it did not clearly provide an advantage over expert optical diagnosis in this specialist setting. The findings indicate that the benefit of AI-assisted colonoscopy may depend on the expertise and clinical setting in which it is deployed.
BACKGROUND: Individuals with Lynch syndrome undergo regular colonoscopic surveillance because of their increased risk of colorectal cancer. Artificial intelligence (AI)-based computer-aided detection (CADe) has improved adenoma detection in average-risk colorectal cancer screening, but evidence in Lynch syndrome surveillance has been limited. The CADLY2 trial evaluated whether AI-assisted colonoscopy could improve adenoma detection and whether computer-aided optical diagnosis (CADx) could accurately differentiate neoplastic from non-neoplastic colorectal lesions.
DETAILS: This international, multicentre, open-label, randomized controlled trial was conducted at nine specialized hereditary cancer surveillance centres in Belgium, Germany, the Netherlands, and Spain. Adults aged 18 years or older with genetically confirmed Lynch syndrome undergoing surveillance colonoscopy were randomly assigned to high-definition white-light (HD-WL) colonoscopy alone or HD-WL colonoscopy assisted by the CAD EYE AI system. CADe was used during withdrawal to identify lesions, while CADx was used after lesion detection to assist with optical differentiation. The primary outcome was adenoma detection rate, defined as the proportion of patients with at least one histopathologically confirmed adenoma.
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Between May 9, 2023, and October 30, 2025, 757 patients were randomly assigned to HD-WL colonoscopy (377) or AI-assisted colonoscopy (380). The primary analysis included 733 patients: 369 in the HD-WL group and 364 in the AI-assisted group. Adenoma detection occurred in 30.9% of patients undergoing HD-WL colonoscopy compared with 33.8% receiving AI-assisted colonoscopy. The odds ratio was 1.14 (95% CI, 0.83-1.57; P=0.41), indicating no statistically significant improvement in adenoma detection with CADe. In the lesion-level analysis, CADx differentiated neoplastic from non-neoplastic lesions with a sensitivity of 85.9% (95% CI, 82.0-89.1) and specificity of 91.4% (95% CI, 89.4-93.0). Three adverse events occurred in the AI-assisted group, including two mild post-polypectomy bleeding events and one serious pulmonary embolism or deep venous thrombosis considered unrelated to the procedure. No adverse events were reported in the HD-WL group.
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Source: Hüneburg, R., van Bokhorst, Q. N. E., Pellisé, M., et al. Artificial intelligence-assisted detection and optical differentiation of colorectal lesions in Lynch syndrome surveillance (CADLY2): a multicentre, open-label, randomised controlled superiority trial. The Lancet Gastroenterology & Hepatology. 2026; 11(10): 875-886. Published: October, 2026. DOI: 10.1016/S2468-1253(26)00163-9.
Exercise Therapy and Education Improve Short-Term Outcomes After ACL Reconstruction
A randomized trial of 184 young adults with persistent knee symptoms after ACL reconstruction found that 4 months of supervised exercise and education produced greater short-term improvements in pain, function, and quality of life than minimal education and self-directed exercise. Benefits narrowed by 12 months, while no difference in cartilage thickness was observed between groups.
KEY FINDINGS: In young adults with persistent knee symptoms after ACL reconstruction, a 4-month supervised exercise and education program produced greater short-term improvements in knee pain, symptoms, function, and quality of life than minimal education and self-directed exercise. The treatment difference diminished by 12 months, and no difference in cartilage thickness was observed, providing trial evidence that the supervised exercise program did not result in detectable adverse changes in this structural measure over the study period. The findings support the potential value of structured rehabilitation for patients who continue to experience knee problems after the usual postoperative rehabilitation period.
BACKGROUND: Persistent pain, functional limitations, and reduced quality of life can continue in young adults after anterior cruciate ligament reconstruction (ACLR), increasing concern about early post-traumatic knee osteoarthritis. The SUPER-Knee randomized clinical trial evaluated whether a structured, physiotherapist-supervised exercise and education program could improve knee symptoms and function in young adults with ongoing problems after ACLR, while also examining whether exercise affected knee cartilage.
DETAILS: The randomized clinical trial enrolled 184 adults aged 18 to 40 years who remained symptomatic 9 to 36 months after ACL reconstruction. Participants were randomly assigned to either a 4-month individualized program of twice-weekly, physiotherapist-supervised strengthening and neuromuscular exercise with education or a minimal-intervention group receiving a one-time education session and advice for self-directed exercise. The primary outcome was change in the Knee injury and Osteoarthritis Outcome Score (KOOS4), which incorporates pain, symptoms, function in sports and recreational activities, and knee-related quality of life. Secondary outcomes included patient-perceived recovery, thigh muscle strength, and MRI measures of cartilage.
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Of the 184 participants, 92 were assigned to each group; 178 participants (97%) completed the 4-month assessment and 174 (95%) completed the 12-month assessment. At 4 months, KOOS4 scores improved by 14.1 points in the supervised exercise group compared with 9.3 points in the minimal-intervention group, corresponding to an adjusted between-group difference of 4.8 points (95% CI, 1.4 to 8.2). The difference was smaller at 12 months, with an adjusted between-group difference of 1.4 points (95% CI, -2.0 to 4.8). Participants receiving supervised exercise also had greater improvements in thigh muscle strength and were more likely to report that their knee had improved. The odds of reporting improvement were 5.2 times higher at 4 months (95% CI, 2.7 to 10.0) and 2.5 times higher at 12 months (95% CI, 1.3 to 4.9). MRI assessment showed no between-group difference in cartilage thickness.
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Source: Culvenor, A. G., Bruder, A. M., West, T., et al. XXExercise Therapy and Education for Young Adults With Persistent Knee Problems After Anterior Cruciate Ligament Reconstruction: A Randomized Clinical Trial. Annals of Internal Medicine. Published: September 29, 2026. DOI: 10.7326/ANNALS-26-02460.
Palliative Extracorporeal Membrane Oxygenation Decannulation: An Ethical, Evidence-Based Approach
A structured approach to ECMO de-escalation and decannulation can reduce practice variability while incorporating patient and family preferences. Proactive symptom management may improve the patient and family experience, supporting a more comfortable and dignified end-of-life journey.
KEY FINDINGS: A structured, interprofessional approach to palliative ECMO de-escalation can reduce variability in end-of-life practice and support more consistent symptom management and communication. Incorporating patient and family preferences into the process, together with proactive symptom management and staff debriefing, was associated with a more comfortable and dignified end-of-life experience in this quality-improvement setting.
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is an invasive, potentially lifesaving therapy associated with complications involving multiple organ systems. When ECMO is no longer considered beneficial, de-escalation or decannulation may be required as part of a transition to comfort-focused care and natural death. At a tertiary care facility with 64 beds using ECMO, variability was identified in ECMO initiation, communication with patients and families, determination of nonbeneficial therapy, and symptom management during de-escalation.
DETAILS: This quality-improvement project integrated palliative care, reviewed existing literature on best practices, and established an interprofessional task force focused on ECMO de-escalation. New clinical guidelines were developed to provide a consistent, evidence-based framework for communication, decision-making, symptom management, and de-escalation/decannulation. The initiative was designed to reduce practice variability while improving the experience of patients, families, and clinicians during transition to comfort-directed care.
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Implementation of the guidelines decreased practice variability and reduced patient and family stress and discomfort during ECMO de-escalation and decannulation. Team members reported decreases in symptoms of secondary trauma and moral distress associated with these situations. They also reported improved delivery of end-of-life care, including family education and support, patient advocacy, and symptom management. Family members valued greater attention to both patient and family well-being, while structured staff debriefings supported reflection and identification of opportunities for improvement.
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Source: Arbour, R., Abate, M., Garcia, O., et al. Palliative Extracorporeal Membrane Oxygenation Decannulation: An Ethical, Evidence-Based Approach. Critical Care Nurse. 2026; 46(4): 17-28. Published: August 1, 2026. DOI: 10.4037/ccn2026166.
Real-World Study Finds No Significant Difference in Heart Failure Risk Between Biosimilar and Reference Trastuzumab
In real-world practice, trastuzumab biosimilars were not associated with a statistically significant increase in heart failure compared with reference trastuzumab, supporting their cardiac safety. However, older age, anthracycline use, and greater comorbidity burden remain important risk factors, and larger studies are needed to assess cardiac safety differences among individual biosimilars.
KEY FINDINGS: In this large real-world cohort of patients with early-stage HER2-positive breast cancer, biosimilar trastuzumab use increased markedly between 2018 and 2024 without a statistically significant difference in heart failure risk compared with reference trastuzumab. Overall heart failure occurred in 5.9% of the study population. Comorbidity burden and older age were associated with higher heart failure risk, emphasizing the importance of cardiovascular risk assessment during HER2-directed therapy. Because this was a retrospective claims-based study, longer follow-up and additional real-world studies are needed to further evaluate long-term cardiac outcomes.
BACKGROUND: Trastuzumab is an important treatment for HER2-positive breast cancer, but cardiac dysfunction, including heart failure, remains a recognized safety concern. Biosimilar trastuzumab products have expanded treatment access and may reduce costs, although real-world data comparing their cardiac safety with the reference product remain limited. This study evaluated the uptake of biosimilar trastuzumab and compared heart failure risk between patients receiving biosimilar and reference trastuzumab in routine clinical practice.
DETAILS: The investigators analyzed patients aged ≥18 years with breast cancer who received trastuzumab between 2018 and 2024 using the IQVIA PharMetrics Plus Closed Health Plan Claims database. Patients who underwent breast cancer surgery within the first year after diagnosis were considered to have early-stage disease. Individuals with a heart failure diagnosis before breast cancer surgery were excluded. Trastuzumab products were identified using Healthcare Common Procedure Coding System Level II codes, while heart failure was identified using International Classification of Diseases codes. The analysis used multivariable cause-specific Cox proportional hazards regression to evaluate the association between trastuzumab type and subsequent heart failure risk. The study included 5,135 patients, of whom 43.9% received reference trastuzumab.
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Use of biosimilar trastuzumab increased substantially during the study period, from 0% in 2018 to 71.3% in 2024 (P<0.001). Overall, heart failure occurred in 5.9% of patients, including 5.5% of those receiving reference trastuzumab and 6.3% of those receiving biosimilar trastuzumab (P=0.26). After adjustment for relevant factors, there was no statistically significant difference in heart failure risk between biosimilar and reference trastuzumab (adjusted HR, 1.16; 95% CI, 0.92-1.46). In contrast, patients with a Charlson Comorbidity Index score ≥2 had a higher heart failure risk than those with a score of 0 (adjusted HR, 1.52; 95% CI, 1.11-2.08). Older age was also associated with greater risk: compared with patients aged 18-54 years, the adjusted HR was 1.61 (95% CI, 1.19-2.19) for those aged 65-74 years and 1.95 (95% CI, 1.29-2.96) for those aged ≥75 years.
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Source: Jackson, I., Zhang, N., Sullivan, M., et al. Real-World Cardiotoxicity of Biosimilar versus Reference Trastuzumab in Early HER2-Positive Breast Cancer. JACC: CardioOncology. Published: September 10, 2026. DOI: 10.1016/j.jaccao.2026.07.009.
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