Archives
RCT: Continuing Aspirin vs. Antiplatelet Cessation Before Surgery Did Not Reduce Ischemic Events in Patients With Coronary Stents Over 1 Year Post-Implantation
7 Sep, 2024 | 12:29h | UTCStudy Design and Population: This randomized controlled trial (ASSURE-DES) investigated the perioperative management of antiplatelet therapy in 926 patients with coronary drug-eluting stents (DES) undergoing low-to-intermediate-risk noncardiac surgery. The patients, at least one year post-stent implantation, were randomized to continue aspirin monotherapy or stop all antiplatelet therapy five days prior to surgery.
Main Findings: The study found no significant difference in the primary composite outcome (death, myocardial infarction, stent thrombosis, or stroke) between the aspirin monotherapy group (0.6%) and the no antiplatelet group (0.9%). However, minor bleeding was more frequent in the aspirin group (14.9% vs 10.1%, P=0.027), with no difference in major bleeding.
Implications for Practice: These results suggest that for stable patients with DES undergoing noncardiac surgery, temporarily discontinuing aspirin may be a safe option, as continuing aspirin did not reduce ischemic events but did increase minor bleeding risk. Further research is needed to assess outcomes in higher-risk surgical settings.
News Release: SCOFF Trial Confirms Fasting Not Necessary Before Cardiac Catheterisation Procedures
7 Sep, 2024 | 10:10h | UTC1 September 2024 – London, United Kingdom – New findings from the SCOFF trial, presented at ESC Congress 2024, suggest that fasting prior to minimally invasive cardiac catheterisation procedures under conscious sedation does not increase the risk of complications. The trial supports reconsidering current guidelines on pre-procedural fasting.
Key Points for Physicians:
– No increased complications: The SCOFF trial found no significant difference in adverse outcomes, such as aspiration pneumonia or hypoglycemia, between patients who fasted and those who ate normally before cardiac catheterisation.
– Improved patient satisfaction: Patients who did not fast reported higher satisfaction, with fewer complaints of discomfort and hunger.
– Potential guideline change: These findings, in line with previous studies like CHOW-NOW and TONIC, challenge the necessity of fasting before such procedures.
The trial’s lead investigator, Dr. David Ferreira (John Hunter Hospital, Australia), emphasized that avoiding fasting may improve patient experience without increasing risks, making it time to reconsider fasting guidelines for these procedures.
Study Overview:
– Trial design: Prospective, randomized, open-label, with blinded endpoint assessment.
– Participants: 716 patients undergoing coronary angiography, coronary intervention, or cardiac implantable electronic device procedures.
– Primary endpoint: Composite of hypotension, aspiration pneumonia, hyperglycemia, and hypoglycemia, showing a lower event rate in the non-fasting group (12.0%) compared to the fasting group (19.1%).
These results are likely to influence future clinical practice, providing greater flexibility for both patients and healthcare systems.
RCT: More Extensive Lymph Node Removal Does Not Improve Outcomes in Right-Sided Colon Cancer Surgery
7 Sep, 2024 | 09:56h | UTCStudy Design and Population: This multicenter, open-label, randomized controlled trial (RELARC) evaluated the efficacy of complete mesocolic excision (CME) versus D2 lymphadenectomy for right-sided colon cancer. Conducted across 17 hospitals in China, the study enrolled 1,072 patients with stage T2-T4aNanyM0 or TanyN+M0 disease. Participants were randomized (1:1) to undergo either CME or D2 dissection, and the primary outcome was 3-year disease-free survival (DFS), with 3-year overall survival (OS) as the main secondary outcome.
Main Findings: Among 995 analyzed patients, no significant differences were observed between CME and D2 groups in 3-year DFS (86.1% vs. 81.9%, HR 0.74, P = 0.06) or 3-year OS (94.7% vs. 92.6%, HR 0.70, P = 0.17). While CME trended toward better DFS, the results were not statistically significant.
Implications for Practice: Given the lack of significant survival benefit, the trial supports D2 dissection as the standard surgical approach for right-sided colon cancer. CME may be reserved for cases with evident mesocolic lymph node involvement.
Cohort Study: Short-Course Radiotherapy with CAPOX Shows Favorable Outcomes in High-Risk Locally Advanced Rectal Cancer
7 Sep, 2024 | 09:38h | UTCStudy Design and Population: This Swedish nationwide cohort study examined total neoadjuvant treatment (TNT) for 273 patients with high-risk locally advanced rectal cancer (LARC) using short-course radiotherapy (5×5 Gy) followed by four cycles of CAPOX chemotherapy. Patients were treated between July 2016 and June 2020 across 16 hospitals, with 189 additional patients treated off-study. The study aimed to evaluate the complete response (CR) rate, comparing outcomes with the RAPIDO trial.
Main Findings: The CR rate, including both pathological complete response (pCR) and clinical complete response (cCR), was 24% (LARCT-US group) and 23% (AdmL group), comparable to the RAPIDO trial’s results. Locoregional recurrences were low (6% and 5%, respectively) after 3 years. Neurotoxicity was lower than in RAPIDO, and overall, the treatment was well tolerated. Notably, two fewer chemotherapy cycles did not compromise the CR rate.
Implications for Practice: While the study demonstrates promising outcomes using short-course radiotherapy and four CAPOX cycles for locally advanced rectal cancer (LARC), these findings are based on an observational study, which inherently limits the ability to draw definitive causal conclusions. Despite this, the real-world data suggests that a shorter chemotherapy regimen may be both feasible and effective. Further randomized trials are needed to confirm these results and assess long-term outcomes. Clinicians should cautiously apply this regimen, considering both the evidence and individual patient factors.
RCT: Zasocitinib Achieves Significant Psoriasis Improvement in Moderate to Severe Plaque Psoriasis
6 Sep, 2024 | 22:48h | UTCStudy Design and Population: This phase 2b, double-blind, placebo-controlled trial evaluated the efficacy, safety, and tolerability of zasocitinib, a selective tyrosine kinase 2 (TYK2) inhibitor, in patients with moderate to severe plaque psoriasis. Conducted across 55 centers in the US and Canada, the study enrolled 287 patients aged 18 to 70 years with a Psoriasis Area and Severity Index (PASI) score ≥12, and ≥10% of body surface area affected. Patients were randomized to receive zasocitinib at doses of 2 mg, 5 mg, 15 mg, or 30 mg, or a placebo, over 12 weeks.
Main Findings: At week 12, significant improvements in PASI were observed across all doses of zasocitinib. The primary endpoint of PASI 75 was achieved in 18%, 44%, 68%, and 67% of patients in the 2 mg, 5 mg, 15 mg, and 30 mg zasocitinib groups, respectively, compared to 6% in the placebo group. Higher PASI 90 and PASI 100 responses were also observed, particularly in the 15 mg and 30 mg groups. Adverse events were mild to moderate and occurred in 53% to 62% of patients receiving zasocitinib, compared to 44% for placebo.
Implications for Practice: Zasocitinib shows promise as an effective and well-tolerated oral treatment for moderate to severe plaque psoriasis. Its efficacy in achieving skin clearance (PASI 75 and above) at higher doses suggests potential for broader clinical use, with phase 3 trials warranted for further validation.
RCT: Azithromycin Increases Asthma Remission Rates in Adults With Persistent Uncontrolled Asthma
6 Sep, 2024 | 22:35h | UTCStudy Design and Population: This secondary analysis stems from the Asthma and Macrolides: Azithromycin Efficacy and Safety (AMAZES) trial, a randomized, double-anonymized, placebo-controlled trial. The study involved 335 adults with persistent uncontrolled asthma, who were treated with either azithromycin (500 mg, 3 times weekly) or placebo for 12 months. The goal was to evaluate azithromycin’s impact on asthma remission, defined through clinical and lung function measures.
Main Findings: Azithromycin significantly increased the rate of clinical remission compared to placebo (50.6% vs. 38.9%; P = .032). Clinical remission combined with lung function criteria was also higher in the azithromycin group (50.8% vs. 37.1%; P = .029). Although the complete remission rate (including sputum eosinophil count <3%) trended higher, it did not reach statistical significance (23% vs. 13.7%; P = .058).
Implications for Practice: This secondary analysis suggests that azithromycin, when added to standard asthma therapy, could significantly increase remission rates in adults with persistent uncontrolled asthma, including both eosinophilic and noneosinophilic subtypes.
RCT: AF Screening Does Not Reduce Stroke Hospitalizations in Elderly Patients
6 Sep, 2024 | 22:18h | UTCStudy Design and Population: The GUARD-AF trial was a prospective, randomized controlled trial conducted across 149 primary care sites in the U.S. It enrolled 11,905 participants aged 70 and older, with a median age of 75 years, 56.6% of whom were female. Participants were randomized 1:1 to either screening for atrial fibrillation (AF) using a 14-day continuous electrocardiographic patch monitor or usual care. The primary outcome was all-cause stroke hospitalization, with bleeding as a key safety outcome.
Main Findings: After a median follow-up of 15.3 months, AF diagnosis was higher in the screening group (5%) compared to the usual care group (3.3%), and anticoagulation initiation was also more frequent (4.2% vs. 2.8%). However, the risk of stroke hospitalization was not significantly different between the screening and usual care groups (0.7% vs. 0.6%; HR: 1.10, 95% CI: 0.69-1.75). Similarly, there was no significant difference in bleeding risk (1.0% vs. 1.1%; HR: 0.87, 95% CI: 0.60-1.26).
Implications for Practice: The findings suggest that screening for AF using continuous electrocardiographic monitoring in elderly patients does not reduce stroke hospitalizations despite an increased detection of AF. Given the low event rates and premature termination of enrollment due to COVID-19, further studies are needed to confirm these results and explore alternative strategies for stroke prevention in this population.
RCT: Finerenone Reduces Worsening Heart Failure Events in Patients with Mildly Reduced or Preserved Ejection Fraction
6 Sep, 2024 | 22:03h | UTCStudy Design and Population: This international, double-blind, randomized clinical trial included 6,001 patients with heart failure and a left ventricular ejection fraction of 40% or greater. Patients were randomly assigned to receive either finerenone (20 mg or 40 mg daily) or placebo in addition to standard therapy, with a median follow-up period of 32 months.
Main Findings: The finerenone group experienced a 16% reduction in the composite primary outcome of worsening heart failure events and death from cardiovascular causes compared to placebo (rate ratio, 0.84; 95% CI, 0.74 to 0.95; P=0.007). Specifically, total worsening heart failure events were lower in the finerenone group (rate ratio, 0.82; 95% CI, 0.71 to 0.94; P=0.006), but cardiovascular mortality did not significantly differ between the groups (hazard ratio, 0.93; 95% CI, 0.78 to 1.11). Finerenone was linked to an increased risk of hyperkalemia.
Implications for Practice: Finerenone reduces worsening heart failure events in patients with mildly reduced or preserved ejection fraction, making it a viable addition to standard heart failure therapy. However, clinicians should monitor for hyperkalemia, a known side effect, and the lack of significant mortality benefit highlights the need for further investigation into long-term cardiovascular outcomes.
RCT: Vutrisiran Reduces Mortality and Cardiovascular Events in Patients with Transthyretin Amyloidosis Cardiomyopathy
6 Sep, 2024 | 21:57h | UTCStudy Design and Population: This double-blind, randomized clinical trial evaluated the efficacy of vutrisiran in 655 patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). Participants were randomly assigned to receive either vutrisiran (25 mg) or placebo every 12 weeks for up to 36 months. The study population included patients both with and without baseline tafamidis treatment.
Main Findings: Vutrisiran treatment significantly reduced the risk of death from any cause and recurrent cardiovascular events compared to placebo (HR: 0.72, 95% CI: 0.56–0.93, p=0.01). In monotherapy patients (no tafamidis), the hazard ratio was 0.67 (95% CI: 0.49–0.93, p=0.02). Vutrisiran also preserved physical function, showing less decline in the 6-minute walk test distance (mean difference: 26.5 meters, p<0.001) and quality of life (mean KCCQ-OS difference: 5.8 points, p<0.001). Adverse events were comparable between groups.
Implications for Practice: Vutrisiran offers a promising treatment option for reducing mortality, cardiovascular events, and functional decline in ATTR-CM patients. Its favorable safety profile supports its potential use in long-term management.
2024 ESC Guidelines for the Management of Chronic Coronary Syndromes
1 Sep, 2024 | 18:49h | UTCIntroduction: The 2024 guidelines were developed by the European Society of Cardiology (ESC) with the endorsement of the European Association for Cardio-Thoracic Surgery (EACTS). These guidelines provide updated recommendations for the management of chronic coronary syndromes (CCS), focusing on the diagnosis, treatment, and long-term care of patients with stable coronary artery disease (CAD).
Key Points:
1 – History and Risk Assessment:
– Detailed assessment of cardiovascular risk factors, medical history, and symptom characteristics is essential in patients with suspected CCS.
– Symptoms like chest pain triggered by emotional stress, dyspnea on exertion, or fatigue should be considered potential angina equivalents.
2 – Diagnostic Testing:
– Coronary Computed Tomography Angiography (CCTA): Recommended as a first-line diagnostic tool for patients with low to moderate pre-test likelihood of obstructive CAD.
– Stress Imaging: Stress echocardiography, SPECT, PET, or cardiac MRI is recommended for those with moderate to high pre-test likelihood to diagnose myocardial ischemia and estimate the risk of major adverse cardiovascular events (MACE).
3 – Revascularization Indications:
– Symptom Relief: Revascularization is recommended for patients with obstructive CAD who have significant symptoms despite optimal medical therapy.
– Prognostic Benefit: Indicated in patients with left main coronary artery disease, severe three-vessel disease, or two-vessel disease including proximal left anterior descending artery stenosis, particularly if associated with reduced left ventricular function.
– High-Risk Anatomical Features: Revascularization is advised when significant stenosis is present in patients with high-risk anatomical features identified by imaging, especially if non-invasive testing shows a large area of ischemia.
4 – Lifestyle and Risk Management:
– A comprehensive approach to cardiovascular risk reduction, including lifestyle changes (e.g., smoking cessation, diet, and physical activity) and guideline-directed medical therapy, is strongly recommended.
– Home-based cardiac rehabilitation and digital health interventions are suggested to improve long-term adherence to healthy behaviors.
5 – Antianginal and Antithrombotic Therapy:
– Tailoring antianginal therapy based on individual patient characteristics, comorbidities, and local drug availability is recommended.
– Long-term antithrombotic therapy with aspirin or clopidogrel is recommended for patients with prior myocardial infarction or revascularization.
Conclusion: The 2024 ESC guidelines emphasize a patient-centered approach, integrating advanced diagnostic tools and personalized therapeutic strategies to optimize outcomes for patients with chronic coronary syndromes. The guidelines highlight the importance of detailed risk assessment, appropriate use of diagnostic imaging, clear criteria for revascularization, and a strong focus on lifestyle interventions alongside pharmacological management.
Updated ESC Hypertension Guidelines 2024: Intensified Blood Pressure Targets and New Categories – Eur Heart J
31 Aug, 2024 | 19:54h | UTCIntroduction:
The 2024 ESC Guidelines for managing elevated blood pressure (BP) and hypertension were developed by the European Society of Cardiology (ESC) and endorsed by the European Society of Endocrinology (ESE) and the European Stroke Organisation (ESO). These guidelines introduce significant updates to BP management, including more intensive treatment targets and the introduction of a new category for “Elevated BP.”
Key Points:
1 – New Intensive BP Target: For most patients receiving BP-lowering medication, the guidelines now recommend a systolic BP treatment target range of 120-129 mmHg. This marks a significant shift from previous guidelines, which suggested a less aggressive initial target.
2 – New ‘Elevated BP’ Category: The guidelines introduce a new category, “Elevated BP,” defined as a systolic BP of 120-139 mmHg and/or diastolic BP of 70-89 mmHg. This aims to identify more patients at risk of cardiovascular events, such as heart attacks and strokes, before they meet the traditional threshold for hypertension.
3 – Pragmatic BP Management: For patients who cannot tolerate the intensive BP target, the guidelines recommend aiming for a BP that is “as low as reasonably achievable” (ALARA), particularly in frail or older individuals.
4 – Lifestyle Modifications: The guidelines emphasize lifestyle interventions, including dietary changes like potassium supplementation and new exercise recommendations, as first-line strategies for managing BP.
5 – Renal Denervation: For the first time, the guidelines include recommendations on the use of renal denervation—a procedure for patients with resistant hypertension that has not responded to standard treatments. This is not recommended as a first-line treatment but may be considered in specific high-risk cases.
Conclusion:
These new guidelines represent a major update in the management of hypertension, particularly in promoting more aggressive BP targets to reduce cardiovascular risks. The inclusion of a new BP category and recommendations for renal denervation highlight the guidelines’ focus on early intervention and advanced treatment options.
2024 ESC Guidelines for the Management of Atrial Fibrillation – Eur Heart J
31 Aug, 2024 | 19:34h | UTCIntroduction: The 2024 guidelines for the management of atrial fibrillation (AF) were developed by the European Society of Cardiology (ESC) in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS) and other specialized associations. These guidelines aim to provide evidence-based recommendations for the diagnosis, treatment, and management of AF, with a focus on improving patient outcomes through a multidisciplinary approach.
Key Points:
1 – Patient-Centered Care and Education:
– Education directed at patients, caregivers, and healthcare professionals is essential for optimizing shared decision-making. This approach ensures that treatment options are discussed openly, considering both the benefits and risks.
2 – Comorbidity and Risk Factor Management:
– Diuretics are recommended for patients with AF, heart failure (HF), and congestion to alleviate symptoms and improve AF management.
– Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) are recommended for patients with AF and HF, regardless of left ventricular ejection fraction (LVEF), to reduce the risk of hospitalization and cardiovascular death.
3 – Stroke Prevention and Anticoagulation:
– Oral anticoagulation is recommended for all patients with clinical AF and elevated thromboembolic risk, particularly those with a CHA2DS2-VA score of 2 or more.
– Direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists (VKAs) in eligible patients undergoing cardioversion.
4 – Rate and Rhythm Control:
– Beta-blockers, diltiazem, verapamil, or digoxin are recommended as first-choice drugs for heart rate control in patients with AF and LVEF >40%.
– Catheter ablation is recommended as a first-line treatment option in patients with paroxysmal AF to reduce symptoms and prevent AF progression.
Conclusion: The 2024 ESC guidelines emphasize a patient-centered, multidisciplinary approach to AF management, with a strong focus on the early identification and management of comorbidities and risk factors. The guidelines also advocate for the use of DOACs in stroke prevention and recommend specific strategies for rate and rhythm control to enhance patient outcomes.
Updated Guidelines for Potentially Inappropriate Medication Use in Older Adults (2023 AGS Beers Criteria®) – J Am Geriatr Soc
31 Aug, 2024 | 19:20h | UTCIntroduction:
The American Geriatrics Society (AGS) has released the 2023 update to the AGS Beers Criteria®, a critical tool for healthcare professionals aimed at improving the safety of medication prescribing in adults aged 65 and older. The guidelines identify potentially inappropriate medications (PIMs) that should generally be avoided in older adults due to the heightened risk of adverse effects.
Key Points:
1 – Anticholinergic Drugs: First-generation antihistamines (e.g., diphenhydramine) should be avoided due to their high anticholinergic activity, which can lead to confusion, dry mouth, constipation, and other serious side effects, including increased risk of falls and dementia.
2 – Nitrofurantoin: Should be avoided in individuals with a creatinine clearance less than 30 mL/min due to the risk of pulmonary toxicity, hepatotoxicity, and peripheral neuropathy.
3 – Cardiovascular Drugs: Aspirin for primary prevention of cardiovascular disease is not recommended in older adults due to the increased risk of bleeding and lack of clear benefit. Similarly, warfarin is discouraged as an initial treatment for nonvalvular atrial fibrillation or venous thromboembolism in favor of Direct Oral Anticoagulants (DOACs) unless DOACs are contraindicated.
4 – Central Nervous System (CNS) Medications: Benzodiazepines and non-benzodiazepine receptor agonist hypnotics (“Z-drugs”) are associated with increased risks of cognitive impairment, delirium, falls, fractures, and motor vehicle accidents in older adults and should generally be avoided.
5 – Antipsychotics: Should be avoided for the treatment of behavioral problems in dementia or delirium due to the increased risk of stroke and greater rates of cognitive decline and mortality unless required for specific psychiatric conditions like schizophrenia or bipolar disorder.
Conclusion:
The 2023 AGS Beers Criteria® continues to serve as an essential guide for minimizing the risks associated with medication use in older adults. It emphasizes the need for individualized care and the importance of weighing the benefits and risks of medications, particularly in vulnerable populations.
RCT: No Difference in Postoperative Complications Between Continuation and Discontinuation of Renin-Angiotensin System Inhibitors Before Major Surgery – JAMA
31 Aug, 2024 | 19:12h | UTCStudy Design and Population: This multicenter randomized clinical trial included 2,222 patients who had been treated with renin-angiotensin system inhibitors (RASIs) for at least 3 months and were scheduled for major noncardiac surgery at 40 hospitals in France between January 2018 and April 2023. The participants were randomly assigned to either continue RASIs until the day of surgery or to discontinue them 48 hours before surgery.
Main Findings: The trial found no significant difference in the primary outcome—a composite of all-cause mortality and major postoperative complications within 28 days—between the continuation and discontinuation groups (22% in both groups, RR 1.02, 95% CI 0.87-1.19). However, the continuation group experienced a higher incidence of intraoperative hypotension (54% vs. 41%, RR 1.31, 95% CI 1.19-1.44).
Implications for Practice: Continuation of RASIs before major noncardiac surgery does not increase the risk of postoperative mortality or major complications, but it does elevate the risk of intraoperative hypotension. Clinicians should weigh these risks when deciding whether to continue or discontinue RASIs before surgery.
RCT: Beta-Blocker Interruption Post-Myocardial Infarction Increases Cardiovascular Events Without Improving Quality of Life – N Engl J Med
31 Aug, 2024 | 19:04h | UTCStudy Design and Population: This multicenter, open-label, randomized, noninferiority trial included 3,698 patients across 49 sites in France. Participants had a history of myocardial infarction, a left ventricular ejection fraction of at least 40%, and had not experienced a cardiovascular event in the past six months. The study compared outcomes between patients who either interrupted or continued long-term beta-blocker therapy, with a minimum follow-up of one year.
Main Findings: Interruption of beta-blocker treatment resulted in a higher incidence of adverse cardiovascular events (23.8%) compared to continuation (21.1%), with a hazard ratio of 1.16 (95% CI, 1.01 to 1.33). The difference did not meet the criteria for noninferiority (P=0.44). Additionally, there was no significant improvement in quality of life among patients who discontinued beta-blockers.
Implications for Practice: The findings suggest that in patients with a history of myocardial infarction and stable cardiovascular health, continuing beta-blocker therapy is preferable to interruption. Discontinuation may increase the risk of adverse cardiovascular outcomes without offering quality of life benefits, supporting the ongoing use of beta-blockers in this population.
Network Meta-Analysis: Potent Corticosteroids, JAK Inhibitors, and Tacrolimus 0.1% Among the Most Effective Topical Treatments for Eczema – Cochrane Library
25 Aug, 2024 | 12:03h | UTCStudy Design and Population: This network meta-analysis included 291 randomized controlled trials involving 45,846 participants with varying eczema severity. The trials primarily focused on adults in high-income countries and assessed various topical anti-inflammatory treatments over a median duration of 21 to 28 days. The study aimed to compare the efficacy and safety of these treatments.
Main Findings: Potent topical corticosteroids (TCS), JAK inhibitors, and tacrolimus 0.1% were consistently ranked as the most effective treatments for reducing eczema symptoms and signs. In contrast, phosphodiesterase-4 (PDE-4) inhibitors like crisaborole 2% and mild TCS were among the least effective. Notably, tacrolimus, pimecrolimus, and crisaborole were more likely to cause local adverse effects such as burning and stinging, while short-term TCS use did not show an increased risk of skin thinning, although long-term use did.
Implications for Practice: The findings suggest that potent TCS, JAK inhibitors, and tacrolimus 0.1% are effective for short-term eczema control. However, given the risk of skin thinning with long-term TCS use and potential adverse effects with certain treatments, clinicians should consider patient preferences, treatment availability, and cost when selecting therapies.
Clinical Trial Follow-Up: Continued Imatinib Significantly Extends Survival and Delays Resistance in Advanced GIST – The Lancet Oncology
25 Aug, 2024 | 11:55h | UTCStudy Design and Population: This exploratory long-term follow-up of the BFR14 open-label, multicenter, randomized phase 3 trial involved patients with advanced gastrointestinal stromal tumors (GIST) across 17 cancer centers in France. The trial included patients aged 18 years or older with stable disease after 1, 3, or 5 years of treatment with imatinib. Participants were randomized to either continue or discontinue imatinib until disease progression, with primary endpoint analysis focused on progression-free survival (PFS).
Main Findings: Imatinib continuation significantly extended PFS compared to discontinuation, with median PFS ranging from 27.8 to over 67.0 months in the continuation group versus 6.1 to 12.0 months in the interruption group, depending on the duration of prior treatment (p-values <0.002). Additionally, continuing imatinib delayed resistance and improved overall survival, particularly notable after 3 years of treatment, with a median overall survival of 134.0 months compared to 104.0 months in the discontinuation group (HR 0.40, p=0.0096).
Implications for Practice: These findings strongly discourage the interruption of imatinib in GIST patients who are stable or responding to treatment, as it leads to worse long-term outcomes, including quicker disease progression and increased resistance to the therapy.
RCT: Cold Snare EMR Reduces Major Adverse Events but Increases Residual Adenoma in Large Nonpedunculated Colorectal Polyps – Gastroenterology
25 Aug, 2024 | 11:45h | UTCStudy Design and Population: This multicentric randomized controlled trial (RCT) involved 19 centers in Germany and included 363 patients with 396 large nonpedunculated colorectal polyps (≥20 mm). Participants were randomly assigned to undergo either cold snare endoscopic mucosal resection (EMR) or the traditional hot snare EMR. The study aimed to compare the safety and effectiveness of cold versus hot snare EMR.
Main Findings: Cold snare EMR significantly reduced the incidence of major adverse events (AEs), with a major AE rate of 1.0% compared to 7.9% in the hot snare group. This included significant reductions in perforation and postendoscopic bleeding rates. However, cold snare EMR was associated with a higher rate of residual adenoma at follow-up, with 23.7% of cases compared to 13.8% in the hot snare group. The increased rate of residual adenoma was particularly noted in larger lesions (≥4 cm) and those with high-grade dysplasia.
Implications for Practice: Cold snare EMR offers a safer alternative to hot snare EMR for resecting large nonpedunculated colorectal polyps, particularly in terms of reducing major AEs. However, the higher rate of residual adenoma indicates that cold snare EMR should be used selectively, especially for smaller polyps or less likely to have advanced histology. Further research is needed to refine lesion selection criteria and to explore technical modifications that could improve the efficacy of cold snare EMR.
Phase 2b Trial: Nicardipine Implants Show Promise in Reducing Vasospasm After Aneurysmal Subarachnoid Hemorrhage – JAMA Neurology
25 Aug, 2024 | 11:29h | UTCStudy Design and Population: This single-masked, multicenter, randomized clinical trial involved 41 patients with World Federation of Neurological Surgeons grade 3 or 4 aneurysmal subarachnoid hemorrhage (aSAH) from six neurovascular centers in Germany and Austria. The patients were randomized to either receive localized nicardipine release implants during microsurgical aneurysm repair plus standard care or standard care alone.
Main Findings: The incidence of moderate to severe angiographic vasospasm (aVS) between days 7 and 9 after aSAH was significantly lower in the implant group (20%) compared to the control group (58%; P = .02). Additionally, fewer patients in the implant group required vasospasm rescue therapy (10% vs. 58%; P = .002). However, at 52 weeks, no significant difference was observed in favorable outcomes between the groups (84% in the implant group vs. 67% in the control group; P = .27).
Implications for Practice: Nicardipine implants show promise in reducing vasospasm-related complications following aSAH, suggesting a potential benefit for early postoperative management. However, their impact on long-term clinical outcomes requires further investigation in larger phase 3 trials to determine the overall benefit and cost-effectiveness of this intervention.
Cluster-Randomized Trial: Twice-Yearly Azithromycin Reduces Mortality in Children Aged 1 to 59 Months in Niger – New England Journal of Medicine
24 Aug, 2024 | 19:44h | UTCStudy Design and Population: This adaptive cluster-randomized trial evaluated the impact of twice-yearly azithromycin distribution on childhood mortality in rural communities in Niger. A total of 1273 communities were assigned to three groups: children aged 1 to 59 months receiving azithromycin, infants aged 1 to 11 months receiving azithromycin and placebo for older children, and a placebo group. The study included 382,586 children and followed mortality over 419,440 person-years.
Main Findings: The study found a significant 14% reduction in mortality among children aged 1 to 59 months in the azithromycin group compared to placebo (11.9 vs. 13.9 deaths per 1000 person-years; P<0.001). However, azithromycin did not significantly reduce mortality in infants aged 1 to 11 months when compared to placebo (22.3 vs. 23.9 deaths per 1000 person-years).
Implications for Practice: Azithromycin distribution to children aged 1 to 59 months effectively reduces mortality in rural sub-Saharan Africa. However, targeting only infants may not yield significant benefits. Continuous monitoring for antimicrobial resistance is essential.
RCT: : Belzutifan Improves Progression-Free Survival and Objective Response Compared to Everolimus in Advanced Renal-Cell Carcinoma – N Engl J Med
24 Aug, 2024 | 16:48h | UTCStudy Design and Population: This phase 3, multicenter, open-label trial included 746 participants with advanced clear-cell renal-cell carcinoma who had previously undergone immune checkpoint and antiangiogenic therapies. Participants were randomly assigned to receive either belzutifan (120 mg daily) or everolimus (10 mg daily) until disease progression or intolerable toxicity occurred.
Main Findings: The median progression-free survival was identical at 5.6 months for both groups. However, at 18 months, a significantly higher percentage of participants in the belzutifan group (24.0%) remained progression-free compared to the everolimus group (8.3%, P=0.002). Belzutifan also led to a significantly higher objective response rate (21.9% vs. 3.5%, P<0.001). Median overall survival was similar between the groups, with no significant difference (21.4 months vs. 18.1 months, P=0.20).
Implications for Practice: Belzutifan offers a substantial benefit in progression-free survival and objective response rate over everolimus in patients with advanced renal-cell carcinoma post previous therapies. It was well-tolerated, with safety comparable to everolimus, suggesting its potential as a preferred treatment option in this patient population.
Meta-Analysis: High-Dose Psilocybin Shows Small Advantage Over Escitalopram for Depression – The BMJ
24 Aug, 2024 | 16:41h | UTCStudy Design and Population: This systematic review and Bayesian network meta-analysis evaluated the effectiveness of oral monotherapy with psychedelics (psilocybin, LSD, MDMA, ayahuasca) compared to escitalopram in adults with depressive symptoms. The analysis included 15 trials with psychedelics and 5 trials with escitalopram, covering a total of 811 participants in psychedelic trials and 1968 in escitalopram trials.
Main Findings: The analysis revealed that only high-dose psilocybin demonstrated a significant improvement in depressive symptoms compared to placebo when considered in the context of antidepressant trials, but the effect size was small (standardized mean difference of 0.31). High-dose psilocybin also outperformed escitalopram (10 mg and 20 mg), with a mean difference exceeding the minimal important difference. However, the placebo response was generally lower in psychedelic trials compared to antidepressant trials, suggesting potential overestimation of effect sizes in psychedelic studies.
Implications for Practice: The findings suggest that while high-dose psilocybin may offer a small advantage over escitalopram for treating depression, the overall effect size is comparable to traditional antidepressants. The results highlight the importance of considering the impact of blinding and placebo response in psychedelic trials, and suggest that improved blinding and standardized psychotherapies could help better assess the true efficacy of these treatments.
Retrospective Study: AI Tool Accurately Excludes Pathology in Up to 52.7% of Unremarkable Chest Radiographs with Low Critical Misses – Radiology
24 Aug, 2024 | 16:14h | UTCStudy Design and Population: This retrospective study assessed the effectiveness of a commercial AI tool in correctly identifying unremarkable chest radiographs, thus potentially reducing the workload in radiology departments. The study analyzed 1,961 chest radiographs from adult patients (median age: 72 years) across four Danish hospitals. The radiographs were labeled as remarkable or unremarkable by thoracic radiologists, and the AI tool’s performance was evaluated at varying sensitivity thresholds.
Main Findings: The AI tool demonstrated a specificity of 24.5% to 52.7% at sensitivity thresholds of 99.9% to 98.0%, respectively, effectively excluding pathology in unremarkable chest radiographs. At sensitivities of 95.4% or higher, the AI had equal or lower rates of critical misses compared to radiology reports, with the AI missing only 2.2% of critical findings compared to 1.1% by radiologists at similar sensitivity levels.
Implications for Practice: The results suggest that AI tools could autonomously report up to 52.7% of unremarkable chest radiographs, potentially reducing radiologist workload without compromising patient safety. However, prospective studies are necessary to confirm these findings and optimize AI deployment in clinical practice.
Meta-Analysis: ERAS Protocols Improve Recovery and Reduce Complications After Emergency Laparotomy – Am J Surg
18 Aug, 2024 | 19:32h | UTCStudy Design and Population: This systematic review and meta-analysis assessed the effects of Enhanced Recovery After Surgery (ERAS) protocols compared to standard care (SC) in patients undergoing emergency laparotomy. The analysis included six randomized clinical trials (RCTs) with a total of 509 patients.
Main Findings: The ERAS group showed a reduction in length of hospital stay (mean difference: -2.92 days) and quicker recovery milestones, such as time to ambulation (mean difference: -1.67 days) and first bowel opening (mean difference: -1.26 days). The ERAS protocols were also associated with lower rates of pulmonary complications (odds ratio [OR]: 0.43) and surgical site infections (OR: 0.33). Mortality rates were similar between the ERAS and SC groups.
Implications for Practice: These findings suggest that ERAS protocols may enhance recovery and reduce complications in patients undergoing emergency laparotomy. Implementation of these protocols could be beneficial in emergency surgical settings, where feasible.
Systematic Review: Nasogastric Feeding Increases Diarrhea and Pain Compared to Nasojejunal Feeding in Acute Pancreatitis – BMC Gastroenterol
18 Aug, 2024 | 19:23h | UTCStudy Design and Population: This systematic review and meta-analysis compared the safety and efficacy of nasogastric (NG) versus nasojejunal (NJ) feeding initiated within 48 hours of hospital admission in patients with moderate to severe acute pancreatitis. The analysis included four randomized controlled trials (RCTs) involving a total of 217 patients.
Main Findings: The review found no significant difference in mortality between NG and NJ feeding groups. However, NG feeding was associated with a higher incidence of diarrhea (RR 2.75, P = 0.02) and pain (RR 2.91, P = 0.002). The risk of infection was also higher in the NG group (6.67% vs. 3.33%, P = 0.027). No significant differences were observed in the need for surgical intervention, the requirement for parenteral nutrition, or the success rates of feeding procedures.
Implications for Practice: The findings suggest that while NG feeding does not increase mortality in acute pancreatitis, it is associated with higher rates of certain complications, particularly diarrhea and pain. Clinicians should consider these risks when choosing a feeding strategy for patients with acute pancreatitis, especially within the critical early 48-hour period post-admission.