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Meta-Analysis: Effects of extracorporeal CO2 removal on gas exchange and ventilator settings in critically ill adults – Crit Care

27 May, 2024 | 20:28h | UTC

Summary: Study Design and Population: This systematic review and meta-analysis included 49 studies (3 RCTs, 46 observational studies) involving 1672 critically ill adults undergoing extracorporeal carbon dioxide removal (ECCO2R) for respiratory failure between January 2000 and March 2022.

Main Findings: ECCO2R significantly reduced PaCO2, plateau pressure, and tidal volume, while increasing pH across all patient groups. Adverse event rate was 19%. The three RCTs did not show mortality benefits but indicated longer ICU and hospital stays.

Implications for Practice: ECCO2R improves gas exchange and reduces ventilation invasiveness, especially in ARDS and lung transplant patients. However, due to the lack of mortality benefits and increased adverse events, further studies are needed to identify patient groups that could benefit most from ECCO2R.

 

Reference (link to free full-text):

Stommel AM et al. (2024). Effects of extracorporeal CO2 removal on gas exchange and ventilator settings: a systematic review and meta-analysis. Critical Care, 28(146). DOI: 10.1186/s13054-024-04927-x.

 


Randomized Clinical Trial: Aficamten improves peak oxygen uptake in symptomatic obstructive hypertrophic cardiomyopathy – N Engl J Med

27 May, 2024 | 20:24h | UTC

Study Design and Population: This phase 3, double-blind trial randomized 282 adults with symptomatic obstructive hypertrophic cardiomyopathy (HCM) to receive aficamten or placebo for 24 weeks. The primary outcome was the change in peak oxygen uptake, with secondary outcomes including changes in the Kansas City Cardiomyopathy Questionnaire score and New York Heart Association functional class.

Main Findings: Aficamten significantly increased peak oxygen uptake by 1.7 ml/kg/min (95% CI, 1.0 to 2.4; P<0.001) compared to placebo. Improvements were also seen in all secondary outcomes. The incidence of adverse events was similar between the groups.

Implications for Practice: Aficamten shows promise in improving exercise capacity and symptoms in patients with obstructive HCM, potentially offering a new therapeutic option. Further research may confirm its long-term benefits and safety.

 

Reference (link to abstract – $ for full-text):

Maron, M. S., et al. (2024). Aficamten for Symptomatic Obstructive Hypertrophic Cardiomyopathy. New England Journal of Medicine. DOI: 10.1056/NEJMoa2401424.

 


AAN updated practice guidelines for epilepsy and pregnancy – Neurology

27 May, 2024 | 20:23h | UTC

Introduction:

The American Academy of Neurology (AAN), the American Epilepsy Society (AES), and the Society for Maternal-Fetal Medicine (SMFM) have published a comprehensive guideline focusing on the management of epilepsy in individuals of childbearing potential. This guideline addresses the use of antiseizure medications (ASMs) and the impact of folic acid supplementation on major congenital malformations (MCMs), perinatal outcomes, and neurodevelopmental outcomes.

 

Key Points:

  1. Optimizing ASM Therapy Preconceptionally: Clinicians should recommend ASMs and doses that optimize both seizure control and fetal outcomes should pregnancy occur, ideally starting this process preconceptionally.
  2. Minimizing Convulsive Seizures During Pregnancy: It is crucial to minimize convulsive seizures in pregnant individuals to reduce risks to both the parent and the fetus.
  3. Monitoring and Adjusting ASM Levels: ASM levels should be monitored throughout pregnancy, and doses should be adjusted based on serum levels and seizure control.
  4. Preferred ASMs for Pregnancy: Lamotrigine, levetiracetam, and oxcarbazepine are recommended when appropriate, as they are associated with lower risks of MCMs compared to other ASMs.
  5. Avoiding Certain ASMs: Valproic acid should be avoided to minimize risks of MCMs, neural tube defects, and poor neurodevelopmental outcomes. Topiramate should also be avoided due to risks of offspring being born small for gestational age.
  6. Folic Acid Supplementation: At least 0.4 mg of folic acid should be prescribed daily preconceptionally and during pregnancy to decrease the risk of neural tube defects and possibly improve neurodevelopmental outcomes.
  7. Counseling on Risks and Monitoring: Clinicians must counsel patients on the potential risks associated with different ASMs and ensure regular fetal screenings to detect congenital malformations early.

 

Conclusion:

These guidelines provide essential, evidence-based recommendations for managing epilepsy in individuals of childbearing potential, emphasizing the importance of preconception planning, careful medication selection, and ongoing monitoring to optimize both maternal and fetal health outcomes.

 

Guideline Reference (link to free full-text):

Pack, A.M., et al. (2024). Practice Guideline From the AAN, AES, and SMFM: Teratogenesis, Perinatal, and Neurodevelopmental Outcomes After In Utero Exposure to Antiseizure Medication. Neurology, 102, e209279. Available at: https://doi.org/10.1212/WNL.0000000000209279​​.

 


Subgroup Analysis Insights: Apixaban vs. aspirin in subclinical atrial fibrillation based on CHA2DS2-VASc score – J Am Coll Cardiol

27 May, 2024 | 20:21h | UTC

Study Design and Population: This study is a subgroup analysis of the ARTESiA trial, which compared the efficacy and safety of apixaban versus aspirin in preventing stroke and systemic embolism (SE) in patients with subclinical atrial fibrillation (SCAF). The analysis focused on 4,012 patients categorized by their baseline CHA2DS2-VASc scores: <4 (39.4%), 4 (33.6%), and >4 (27.0%).

Main Findings: For patients with a CHA2DS2-VASc score >4, apixaban significantly reduced the stroke/SE rate to 0.98%/year compared to 2.25%/year with aspirin, preventing 1.28 strokes/SE per 100 patient-years while causing 0.68 major bleeds. In patients with scores <4, the stroke/SE prevention was minimal (0.12 strokes/SE per 100 patient-years) with a similar rate of major bleeds. Patients with a score of 4 had intermediate results, with a moderate reduction in stroke/SE (0.32 per 100 patient-years) and a comparable risk of major bleeding.

Implications for Practice: The study suggests that for patients with SCAF and a CHA2DS2-VASc score >4, the benefits of apixaban in preventing stroke/SE outweigh the risks of major bleeding. For those with scores <4, aspirin might be a safer option. Patients with a score of 4 fall into an intermediate category, where individual patient preferences should guide the treatment decision.

 

Reference (link to abstract – $ for full-text):

Lopes, R. D., Granger, C. B., Wojdyla, D. M., et al. (2024). Apixaban versus Aspirin According to CHA2DS2-VASc Score in Subclinical Atrial Fibrillation: Insights from ARTESiA. Journal of the American College of Cardiology. Epublished. DOI: 10.1016/j.jacc.2024.05.002.

 


Randomized Clinical Trial: Intravenous acetaminophen in critically ill sepsis patients shows no significant improvement in organ support-free days – JAMA

27 May, 2024 | 20:19h | UTC

Study Design and Population: The ASTER trial was a phase 2b randomized, double-blind, clinical trial conducted between October 2021 and April 2023 across 40 US academic hospitals. The study enrolled 447 adults with sepsis and respiratory or circulatory organ dysfunction within 36 hours of presentation in emergency departments or intensive care units. Participants were randomized to receive either 1 g of acetaminophen intravenously every 6 hours or a placebo for 5 days.

Main Findings: The primary endpoint, days alive and free of organ support (mechanical ventilation, vasopressors, and kidney replacement therapy) up to day 28, showed no significant difference between the acetaminophen group (20.2 days) and the placebo group (19.6 days). Secondary outcomes revealed that the acetaminophen group had significantly lower total, respiratory, and coagulation SOFA scores on days 2 through 4 and a lower rate of acute respiratory distress syndrome within 7 days (2.2% vs 8.5%). No significant interaction was observed between cell-free hemoglobin levels and acetaminophen.

Implications for Practice: While intravenous acetaminophen was safe, it did not significantly enhance the number of days alive and free of organ support in critically ill sepsis patients. The findings suggest that acetaminophen may not be effective in improving organ dysfunction outcomes in this patient population, although certain secondary benefits were noted. Further research might be necessary to explore these secondary findings and potential subgroups that could benefit from acetaminophen treatment.

 

Reference (free for a limited period):

Ware LB, Files DC, Fowler A, et al. (2024). Acetaminophen for Prevention and Treatment of Organ Dysfunction in Critically Ill Patients With Sepsis: The ASTER Randomized Clinical Trial. JAMA. Published online May 19, 2024. doi:10.1001/jama.2024.8772

 


Randomized Clinical Trial: Dequalinium chloride demonstrates noninferiority to metronidazole in treating bacterial vaginosis – JAMA Netw Open

25 May, 2024 | 19:55h | UTC

This randomized clinical trial investigated the efficacy of dequalinium chloride compared to metronidazole for treating bacterial vaginosis in premenopausal women. Conducted across multiple centers from July 2021 to August 2022, the study involved 147 participants who were randomly assigned to receive either dequalinium chloride vaginal tablets or oral metronidazole. The primary outcome measured was the clinical cure rate shortly after treatment completion. Results showed that dequalinium chloride achieved a 92.8% cure rate, which was statistically noninferior to metronidazole’s 93.2% rate. Additionally, dequalinium chloride was better tolerated, with fewer adverse events reported compared to metronidazole. These findings suggest that dequalinium chloride is as effective as traditional antibiotic treatments for bacterial vaginosis and could be considered a viable non-antibiotic alternative due to its similar efficacy and enhanced tolerability.

 

Reference (link to free full-text):

Grzegorz Raba et al. (2024). Efficacy of Dequalinium Chloride vs Metronidazole for the Treatment of Bacterial Vaginosis A Randomized Clinical Trial. JAMA Netw Open, 7(5), e248661. DOI: 10.1001/jamanetworkopen.2024.8661

 


Cohort Study: GLP1 receptor agonist use not associated with significant increase in thyroid cancer risk – The BMJ

25 May, 2024 | 19:51h | UTC

A large Scandinavian cohort study investigated the association between glucagon-like peptide 1 (GLP1) receptor agonist use and thyroid cancer risk in Denmark, Norway, and Sweden from 2007 to 2021. The study compared 145,410 patients treated with GLP1 receptor agonists to 291,667 patients treated with dipeptidyl peptidase 4 (DPP4) inhibitors and included an additional analysis with sodium-glucose cotransporter 2 (SGLT2) inhibitors. Results showed no significant increase in thyroid cancer risk among GLP1 users over a mean follow-up of 3.9 years, with a hazard ratio of 0.93 (95% CI, 0.66 to 1.31) compared to DPP4 inhibitor users. The study utilized nationwide cancer registers and employed an active-comparator, new user design to minimize confounding, using Cox regression models adjusted by propensity score weighting. The findings suggest that while small risk increases cannot be definitively ruled out, the use of GLP1 receptor agonists does not substantially elevate thyroid cancer risk.

 

Reference (link to free full-text):

Björn Pasternak et al. (2024). Glucagon-like peptide 1 receptor agonist use and risk of thyroid cancer: Scandinavian cohort study. BMJ, 385. DOI: https://doi.org/10.1136/bmj-2023-078225

 


APA workgroup update maintains skepticism on pharmacogenomic tools for depression – Am J Psychiatry

25 May, 2024 | 19:47h | UTC

A recent review by the American Psychiatric Association (APA) Council of Research Workgroup on Biomarkers and Novel Treatments revisits the use of pharmacogenomic (PGx) tools for selecting depression treatments. The review assesses new clinical trials and meta-analyses conducted from 2017 to 2022. Of the studies analyzed, few demonstrated significant efficacy in treatment response using PGx tools, with many suffering from methodological flaws such as lack of full blinding and insufficient control measures. Despite some trials showing promise, the overall evidence remains insufficient to support the widespread clinical application of PGx tools in managing major depressive disorder. The Workgroup reaffirms the 2018 conclusions and aligns with the U.S. Food and Drug Administration’s stance, recommending that future research should focus on more rigorous study designs and explore other potential benefits of pharmacogenomics, such as predicting rare adverse drug reactions.

 

Reference (link to abstract – $ for full-text)

Baum ML, et al. (2024). Pharmacogenomic Clinical Support Tools for the Treatment of Depression. American Journal of Psychiatry, Published Online: 30 Apr 2024. DOI: 10.1176/appi.ajp.20230657

 


Cohort Study: Thick liquids not linked to better outcomes in hospitalized patients with dementia—further studies required – JAMA Intern Med

25 May, 2024 | 19:41h | UTC

– This matched cohort study evaluated the impact of thick vs. thin liquids on clinical outcomes in 8916 hospitalized patients aged 65 and older with Alzheimer Disease and Related Dementias (ADRD) and oropharyngeal dysphagia. Conducted across 11 diverse hospitals in New York from January 2017 to September 2022, the study utilized propensity score matching to ensure comparability between the two diet groups based on demographic and clinical characteristics.

– The study found no significant difference in mortality rates between the thick and thin liquid groups (hazard ratio, 0.92; 95% CI, 0.75-1.14; P = .46). Patients on a thick liquid diet were less likely to require intubation (odds ratio [OR], 0.66; 95% CI, 0.54-0.80) but exhibited a higher incidence of respiratory complications such as pneumonia (OR, 1.73; 95% CI, 1.56-1.91).

– The findings suggest that while thick liquids may reduce the need for intubation, they may increase the risk of respiratory complications. These results underscore the necessity for future prospective studies to more definitively ascertain the effectiveness of thick liquids in improving clinical outcomes for this patient population.

 

Reference (link to abstract – $ for full-text):
Makhnevich, A. et al. (2024). Thick Liquids and Clinical Outcomes in Hospitalized Patients With Alzheimer Disease and Related Dementias and Dysphagia. JAMA Intern Med. Published online May 6, 2024. doi:10.1001/jamainternmed.2024.0736

 


Cohort Study: Efficacy of first-line color doppler ultrasound in diagnosing giant cell arteritis – Ann Intern Med

25 May, 2024 | 19:39h | UTC

This prospective multicenter study aimed to evaluate the efficacy of using color Doppler ultrasound of the temporal arteries as the first-line diagnostic tool for Giant Cell Arteritis (GCA) in 165 elderly patients with high clinical suspicion of the disease. The study followed participants over two years, comparing ultrasound results with temporal artery biopsy (TAB) and physician-based clinical diagnosis including other imaging tests. Key findings indicate that ultrasound confirmed GCA in 44% of cases, which was higher compared to TAB (17%) and clinical expertise (21%). The study showed that using ultrasound first can avoid the need for further invasive tests like TAB in patients with positive ultrasound results. The limitations of the study include its small sample size, unblinded test results, and the absence of a universally accepted objective diagnostic standard. However, it highlights the potential of ultrasound in the early and non-invasive diagnosis of GCA, potentially reducing the risk of severe complications by expediting treatment initiation.

 

Reference (link to abstract – $ for full-text):

Guillaume Denis et al. (2023). Diagnostic Strategy Using Color Doppler Ultrasound of Temporal Arteries in Patients With High Clinical Suspicion of Giant Cell Arteritis: A Prospective Cohort Study. Annals of Internal Medicine. DOI: 10.7326/M23-3417.

 


Retrospective Analysis: 7% of outpatients in Massachusetts experience adverse events, predominantly drug-related – Ann Intern Med

25 May, 2024 | 19:37h | UTC

This retrospective study reviewed electronic health records from 11 outpatient sites in Massachusetts during 2018 to assess the incidence and nature of adverse events (AEs) in 3,103 patients. AEs were identified in 7.0% of the patients, translating to 8.6 events per 100 patients annually. Adverse drug events were the most frequent type of AE, constituting 63.8% of events, followed by healthcare-associated infections (14.8%) and surgical or procedural events (14.2%). The severity of these events was notable, with 17.4% being serious and 2.1% life-threatening, though none were fatal. Notably, 23.2% of these events were deemed preventable. The risk of experiencing at least one AE varied significantly by age and race, with higher rates observed among older adults and Black patients compared to other demographics. The study highlights the pressing need for targeted interventions to reduce AEs in outpatient settings.

 

Reference (link to abstract – $ for full-text):

David M. Levine et al. (2023). The Safety of Outpatient Health Care: Review of Electronic Health Records. Annals of Internal Medicine, [insert volume and issue], [insert pages]. DOI: 10.7326/M23-2063

 


RCT: Thrombectomy improves outcomes in acute stroke with large infarcts – N Engl J Med

25 May, 2024 | 19:35h | UTC

Study Design and Population: This randomized clinical trial investigated the efficacy of thrombectomy in combination with standard medical care versus medical care alone in patients with acute stroke and large infarcts. Participants included 333 patients with proximal cerebral vessel occlusion in the anterior circulation, presenting within 6.5 hours of symptom onset. They were randomized in a 1:1 ratio to either undergo thrombectomy or receive only medical care. An Alberta Stroke Program Early Computed Tomographic Score of ≤5 was used to define large infarcts.

Main Findings: The primary outcome, assessed by the modified Rankin scale score at 90 days, showed a median score of 4 in the thrombectomy group compared to 6 in the control group, indicating better functional outcomes with thrombectomy (generalized odds ratio, 1.63; 95% CI, 1.29 to 2.06; P<0.001). Mortality at 90 days was significantly lower in the thrombectomy group (36.1%) compared to the control group (55.5%) with an adjusted relative risk of 0.65. However, thrombectomy was associated with a higher rate of symptomatic intracerebral hemorrhage (9.6% vs. 5.7% in the control group).

Implications for Practice: The findings suggest that thrombectomy, when added to standard medical care, can significantly improve functional outcomes and reduce mortality in patients with large infarct strokes. However, the increased risk of symptomatic intracerebral hemorrhage must be considered when deciding on this intervention. These results support the broader use of thrombectomy in clinical settings with similar patient profiles but underscore the need for careful risk-benefit analysis due to the potential for serious hemorrhagic complications.

 

Reference (link to abstract – $ for full-text):

Costalat, V. et al. (2024). Trial of Thrombectomy for Stroke with a Large Infarct of Unrestricted Size. N Engl J Med, 390(18), 1677-1689. DOI: 10.1056/NEJMoa2314063

 


RCT: Impact of single PSA screening invitation on 15-year prostate cancer mortality – JAMA

25 May, 2024 | 19:01h | UTC

Study Design and Population: This study is a secondary analysis of the Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP), which focused on the long-term effects of prostate-specific antigen (PSA) screening on prostate cancer mortality. It involved 415,357 men aged 50 to 69 years from 573 primary care practices across England and Wales. Participants were randomized to either receive a single invitation for a PSA screening or to a control group receiving standard practice without invitation. The follow-up period concluded on March 31, 2021, after a median duration of 15 years.

Main Findings: The intervention group, which received one PSA screening invitation, showed a prostate cancer mortality rate of 0.69% compared to 0.78% in the control group, translating to a rate ratio of 0.92 and demonstrating a statistically significant but modest reduction in death from prostate cancer. Additionally, the screening led to increased detection rates of low-grade and localized prostate cancer. However, there were no significant differences in detection of more advanced cancer stages between the two groups. All-cause mortality rates were similar across both groups.

Implications for Practice: While the introduction of a single PSA screening invitation was associated with a slight decrease in prostate cancer mortality over 15 years, the absolute reduction was small. These findings suggest that while PSA screening can detect cancer earlier, its impact on long-term survival is limited and should be weighed against the potential for overdiagnosis and overtreatment. Future strategies in prostate cancer screening might need to focus more on risk stratification and personalized screening approaches to maximize benefits and minimize unnecessary interventions.

 

Reference (link to abstract – $ for full-text):

Martin RM et al. (2024). Prostate-Specific Antigen Screening and 15-Year Prostate Cancer Mortality: A Secondary Analysis of the CAP Randomized Clinical Trial. JAMA, 331(17), 1460-1470. DOI: 10.1001/jama.2024.4011

 


Guidelines on the use of intravenous albumin in various clinical settings – CHEST

25 May, 2024 | 18:49h | UTC

The International Collaboration for Transfusion Medicine Guidelines provides comprehensive guidelines on the use of intravenous albumin across various clinical settings, including critical care, cardiovascular surgery, kidney replacement therapy, and complications of cirrhosis. The guideline emphasizes that there are few evidence-based indications supporting the routine use of albumin to improve patient outcomes. Key findings include:

 

1 – Critical Care: Limited recommendations for using albumin in adult, pediatric, and neonatal critical care, primarily advising against its routine use for volume replacement or managing hypoalbuminemia due to low or very low certainty of evidence.

2 – Cardiovascular Surgery: No recommendations for using albumin to prime cardiovascular bypass circuits or for volume replacement due to moderate to very low certainty of evidence.

3 – Kidney Replacement Therapy: Albumin is not suggested for preventing or managing intradialytic hypotension or improving ultrafiltration due to very low certainty of evidence.

4 – Cirrhosis Complications: Some conditional recommendations for using albumin in specific scenarios like large-volume paracentesis and spontaneous bacterial peritonitis due to low certainty of evidence; however, it is generally not suggested for other complications of cirrhosis.

 

Overall, the guidelines advise a cautious approach to albumin use, highlighting the need for more robust evidence to support its broader application in clinical practice.

 

Reference (link to free full-text):

Callum J et al. (2024). Use of Intravenous Albumin: A Guideline From the International Collaboration for Transfusion Medicine Guidelines. CHEST, 2024. DOI: https://doi.org/10.1016/j.chest.2024.02.049.

 


Cohort Study: Impact of decreasing eGFR on serious adverse drug reactions in CKD patients – Am J Kidney Dis

25 May, 2024 | 18:48h | UTC

This prospective cohort study, part of the French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN), involved 3,033 outpatients with moderate to advanced chronic kidney disease (CKD). The study aimed to explore the correlation between estimated glomerular filtration rate (eGFR) and the incidence of serious adverse drug reactions (ADRs). Over a median follow-up of 4.7 years, 360 patients experienced 488 serious ADRs, predominantly kidney and urinary disorders, and hemorrhages, constituting 70% of cases. The study identified antithrombotics and renin-angiotensin system inhibitors as the most common medication classes leading to these ADRs. A significant finding was that a decrease in eGFR is associated with a higher risk of serious ADRs, specifically acute kidney injury and bleeding, which were largely preventable or potentially preventable. The outcomes highlight the critical need for careful drug prescription and monitoring in CKD patients to mitigate serious ADRs.

 

Reference (link to free full-text):

Solène M. Laville et al. (2024). Kidney Function Decline and Serious Adverse Drug Reactions in Patients With CKD. American Journal of Kidney Diseases, 83(5), 601-614.e1. DOI: 10.1053/j.ajkd.2023.09.012.

 


New ACC/AHA Guidelines for the Management of Lower Extremity Peripheral Artery Disease

16 May, 2024 | 11:05h | UTC

Introduction

The 2024 ACC/AHA guidelines, along with several associated societies, highlight the significance of peripheral artery disease (PAD) as a major public health issue, often underestimated, and linked to high risks of amputation and serious cardiovascular events. This document is crucial for clinicians seeking to optimize treatment and improve the quality of life for affected patients.

 

Key Points

1 – Risk Assessment: It is crucial to evaluate risks associated with PAD and health disparities that may impact treatment outcomes.

2 – Diagnosis: Diagnosis of PAD typically involves physical examination, medical history, and the resting ankle-brachial index.

3 – Medical Therapy: Management includes antiplatelet therapy (usually single), high-intensity statins, antihypertensive therapy, diabetes management, and smoking cessation. Rivaroxaban (2.5 mg twice daily) combined with low-dose aspirin (81 mg) has proven effective and can be included in the therapy for patients at low risk of bleeding.

4 – Structured Exercise: A central component of care, including supervised exercise therapy and community-based programs.

5 – Revascularization: Indicated to prevent limb loss in chronic limb-threatening ischemia and can improve quality of life in cases of claudication.

6 – Multidisciplinary Care: Optimized care involves a team of multiple specialties, especially for chronic limb-threatening ischemia.

 

Reference: Gornik HL, et al. (2024). 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS guideline for the management of lower extremity peripheral artery disease. J Am Coll Cardiol. Available at: https://doi.org/10.1016/j.jacc.2024.02.013

 


New Guidelines for the Management of Corticosteroid-Induced Adrenal Insufficiency – J Clin Endocrinol Metab

15 May, 2024 | 11:21h | UTC

Introduction: 

The European Society of Endocrinology and the Endocrine Society have co-published the first joint clinical guideline, focusing on the diagnosis and therapy for glucocorticoid-induced adrenal insufficiency. This document serves as an essential tool for health professionals involved in the care of patients undergoing chronic glucocorticoid therapy.

Key Points:

  • Patient Education: Clinicians are recommended to inform patients about the endocrine effects of glucocorticoid treatment, particularly in relation to adrenal insufficiency.
  • No Tapering in Short-Term Therapies: It is suggested not to taper glucocorticoid therapies of short duration (<3-4 weeks), regardless of the dose.
  • Careful Tapering: For long-term therapies, tapering should be done gradually, especially when approaching physiological daily equivalent doses (e.g., 4-6 mg of prednisone).
  • Monitoring Withdrawal Syndrome: Consideration of glucocorticoid withdrawal syndrome that may occur during tapering, adjusting the dose as needed to alleviate symptoms.
  • Testing for Adrenal Insufficiency: Morning serum cortisol is recommended as the first test in the suspicion of disorders in the recovery of the HPA axis after cessation of glucocorticoids.

These guidelines offer practical and evidence-based guidance for managing patients who develop adrenal insufficiency due to prolonged use of glucocorticoids, emphasizing the importance of patient education and careful monitoring during the tapering process.

 

Reference (link to free full-text):

Beuschlein, F., et al. (2024). European Society of Endocrinology and Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency. The Journal of Clinical Endocrinology & Metabolism. Available at: https://doi.org/10.1210/clinem/dgae250

 


FDA grants approval for Colosense, a noninvasive stool RNA-based test for colorectal cancer screening

11 May, 2024 | 17:48h | UTC

Geneoscopy, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved ColoSense™, a noninvasive stool RNA-based test for colorectal cancer (CRC) screening in adults aged 45 and older who are at average risk for CRC.

 

Test Performance and Specifications:

Sensitivity and Specificity: In the CRC-PREVENT trial, ColoSense demonstrated a sensitivity of 93% for detecting colorectal cancer and 45% sensitivity for detecting advanced adenomas (AA).

Technology: ColoSense employs a multi-target stool RNA (mt-sRNA) approach, detecting colorectal neoplasia-associated RNA markers and occult hemoglobin. This method is designed to overcome variability in test performance that can occur with age-related changes in other biomarkers.

Breakthrough Device Designation: The test has been designated as a Breakthrough Device by the FDA, acknowledging its potential to offer more effective diagnosis compared to existing methods.

Accessibility: ColoSense is intended to facilitate increased screening uptake by providing a noninvasive alternative to traditional colonoscopy, particularly among populations reticent about invasive procedures.

 

Clinical Application:

Screening Recommendations: Approved for individuals at typical average risk for CRC, ColoSense aligns with updated screening guidelines that recommend starting CRC screening at age 45.

Role in Screening Strategy: ColoSense is indicated for use as a screening tool but is not intended to replace diagnostic or surveillance colonoscopy in individuals at high risk for CRC.

 

Geneoscopy is working towards a commercial launch of ColoSense in collaboration with Labcorp (NYSE: LH), aiming to make the test available by late 2024 or early 2025. (link to news release)

 


2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy – J Am Coll Cardiol

11 May, 2024 | 14:20h | UTC

In a significant advancement for the treatment of hypertrophic cardiomyopathy (HCM), the American Heart Association and the American College of Cardiology, along with other leading societies, have released updated guidelines to optimize patient care. Here are the essential updates and recommendations for practicing physicians:

1 – Updated Diagnostic Strategies: The guideline emphasizes the use of advanced imaging techniques and genetic testing to enhance diagnostic accuracy, enabling personalized treatment approaches.

2 – Risk Assessment Tools: Revised tools for sudden cardiac death (SCD) risk assessment are detailed, aiding clinicians in making informed decisions regarding the use of implantable cardioverter-defibrillators (ICDs).

3 – Management of Obstructive HCM: New recommendations for the pharmacological treatment of symptomatic obstructive HCM include the use of disopyramide and advanced therapies such as septal reduction when initial medication does not suffice.

4 – Guidelines on Exercise and Lifestyle: The guidelines provide a nuanced approach to physical activity, recognizing the benefits while outlining the risks for patients with HCM. Detailed advice is offered on managing competitive sports involvement and other lifestyle considerations.

5 – Multidisciplinary Approach: The guidelines advocate for a team-based approach involving specialized HCM centers, ensuring patients benefit from comprehensive expertise and the latest treatment modalities.

6 – Innovations in Treatment: Highlighting new therapeutic options like myosin inhibitors, the guidelines underscore their role in managing obstructive symptoms when traditional medications are inadequate.

7 – Special Populations: Detailed sections on the management of HCM in children and pregnant women, addressing the unique challenges these groups face.

These guidelines represent a cornerstone in the evolving landscape of HCM management, embodying a commitment to enhancing outcomes and quality of life for patients through evidence-based practices and collaborative care.

 

Reference (link to free full-text):

Ommen, S. R., Ho, C. Y., Asif, I. M., et al. (2024). 2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Journal of the American College of Cardiology. https://doi.org/10.1016/j.jacc.2024.02.014

 


RCT: Triple combination of paracetamol, ibuprofen, and dexamethasone reduces morphine use post-hip arthroplasty – Lancet Rheumatol

11 May, 2024 | 14:18h | UTC

Study Design and Population: The RECIPE trial was a randomized, blinded, placebo-controlled multicenter study conducted across nine Danish hospitals to evaluate the effectiveness of non-opioid analgesic combinations in managing postoperative pain following total hip arthroplasty. A total of 1,060 adults scheduled for surgery were enrolled and randomly assigned to one of four treatment groups, receiving combinations of paracetamol, ibuprofen, and dexamethasone. The study’s primary endpoint was the 24-hour intravenous morphine consumption, with a predefined minimal important difference set at 8 mg.

Main Findings: The trial results indicated significant reductions in 24-hour morphine consumption in the group receiving paracetamol, ibuprofen, and dexamethasone combined, compared to other groups, though none reached the minimal important difference. Specifically, this group consumed a median of 15 mg morphine, which was less than the other groups ranging from 16 mg to 24 mg. However, the differences did not meet the study’s threshold for a clinically important effect. Adverse events were lowest in the combined treatment group, suggesting a better safety profile primarily characterized by fewer incidents of nausea, vomiting, and dizziness.

Implications for Practice: The findings support the use of a combined regimen of paracetamol, ibuprofen, and dexamethasone for reducing morphine consumption post-total hip arthroplasty, which could be significant in clinical settings aiming to minimize opioid use. The improved safety profile also highlights the potential benefits of multimodal analgesia. Further research may explore the optimization of dosing schedules and long-term outcomes to enhance patient recovery and satisfaction.

 

Reference (link to abstract – $ for full-text):

Steiness J et al. (2024). Non-opioid analgesic combinations following total hip arthroplasty (RECIPE): a randomised, placebo-controlled, blinded, multicentre trial. The Lancet Rheumatology, 6(4), e205-e215. DOI: 10.1016/S2665-9913(24)00020-1

 


Cohort Study: Late ventricular arrhythmias are rare in STEMI patients without left ventricular dysfunction post-primary PCI – JAMA Netw Open

11 May, 2024 | 14:15h | UTC

Study Design and Population: This cohort study analyzed data from the US National Cardiovascular Data Registry Chest Pain–MI Registry, involving 174,126 adults with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) from 2015 to 2018. The population included a broad demographic with a focus on those experiencing late ventricular tachycardia (VT) or ventricular fibrillation (VF) post-PCI, specifically examining occurrences one day or more after the intervention.

Main Findings: The study found that 8.9% of the patients developed VT or VF after PCI, with 2.4% experiencing these arrhythmias late in the hospitalization period. Among patients with uncomplicated STEMI, late VT or VF with cardiac arrest was exceedingly rare, occurring in only 0.1%. Notably, reduced left ventricular ejection fraction was strongly associated with an increased risk of late VT or VF with cardiac arrest. The presence of late VT or VF significantly correlated with higher in-hospital mortality rates.

Implications for Practice: The findings suggest that late VT or VF after primary PCI in STEMI patients is infrequent, particularly among those without complications. This data supports the potential for safe earlier hospital discharge in uncomplicated cases. However, vigilance is advised due to the significant mortality risk associated with late VT or VF events. Clinicians should consider patient-specific risk factors such as left ventricular function when making discharge decisions.

 

Reference (link to free full-text):

Rymer JA et al. (2024). Ventricular Arrhythmias After Primary Percutaneous Coronary Intervention for STEMI. JAMA Network Open, 7(5), e2410288. DOI: 10.1001/jamanetworkopen.2024.10288.

 


RCT: KarXT (xanomeline–trospium) demonstrates significant symptom reduction in schizophrenia compared to placebo – The Lancet

11 May, 2024 | 13:42h | UTC

Study Design and Population: The EMERGENT-2 study was a randomized, double-blind, placebo-controlled, flexible-dose, 5-week phase 3 trial conducted across 22 inpatient sites in the USA. It targeted adults aged 18–65 years diagnosed with schizophrenia, exhibiting a recent exacerbation in psychotic symptoms. A total of 252 participants, each with a Positive and Negative Syndrome Scale (PANSS) score of 80 or higher and a Clinical Global Impression-Severity score of 4 or more, were enrolled and randomized equally into two groups to receive either the muscarinic receptor agonist KarXT (xanomeline–trospium) or a placebo.

Main Findings: KarXT significantly reduced the PANSS total scores from baseline to week 5, with a mean decrease of 21.2 points compared to 11.6 points in the placebo group (least squares mean difference -9.6; 95% CI -13.9 to -5.2; p<0.0001; Cohen’s d=0.61). All secondary endpoints were also met favorably for KarXT. Common adverse events for KarXT included constipation, dyspepsia, and nausea, but rates of extrapyramidal symptoms were similar between the two groups. The treatment was generally well tolerated with comparable discontinuation rates due to adverse events.

Implications for Practice: These results indicate that KarXT could represent a new class of antipsychotic treatment, diverging from traditional D2 dopamine receptor antagonists and instead leveraging muscarinic receptor activation. The promising outcomes observed in EMERGENT-2 suggest that KarXT has the potential to improve both positive and negative symptoms of schizophrenia while maintaining a favorable safety profile. Ongoing and future studies (EMERGENT-3, EMERGENT-4, and EMERGENT-5) will further elucidate the long-term efficacy and safety of KarXT.

 

Reference (link to abstract – $ for full-text):

Inder Kaul et al. (2023). Efficacy and safety of the muscarinic receptor agonist KarXT (xanomeline–trospium) in schizophrenia (EMERGENT-2) in the USA: results from a randomised, double-blind, placebo-controlled, flexible-dose phase 3 trial. The Lancet, DOI: https://doi.org/10.1016/S0140-6736(23)02190-6

 


Meta-analysis reveals 24% prevalence of eating disorders among individuals with insulin-dependent diabetes – Eat Behav

11 May, 2024 | 13:41h | UTC

This systematic review and meta-analysis evaluated the prevalence of eating disorder symptoms (EDS) in individuals aged 16 and older with insulin-dependent diabetes, covering both type 1 and type 2 diabetes. The study involved an extensive search across several databases including PubMed, Embase, Scopus, PsycINFO, and CINAHL, culminating in the inclusion of 45 studies. The meta-analysis revealed a pooled prevalence of EDS at 24% (95% CI 0.21–0.28), with prevalence reaching 27% (95% CI 0.24–0.31) among studies using the Diabetes Eating Problem Survey-Revised (DEPS-R), the most frequently utilized screening tool. Notably, the prevalence of EDS varied based on the screening tool used and was significantly associated with sex distribution; studies with a higher percentage of female participants (over 58%) reported a higher prevalence of EDS (30% vs. 18%, prevalence ratio 1.7). The study also highlighted a concerning prevalence of insulin omission, reported at 21% (95% CI 0.13–0.33). This analysis underscores the substantial occurrence of eating disorder symptoms among this patient population, emphasizing the need for tailored screening and interventions.

 

Reference (link to abstract – $ for full-text):

Pia E. Niemelä et al. (2024). Prevalence of eating disorder symptoms in people with insulin-dependent-diabetes: A systematic review and meta-analysis. Eating Behaviors, 53, 101863. DOI: https://doi.org/10.1016/j.eatbeh.2024.101863

 


RCT: Cytisinicline shows promising results in enhancing vaping cessation among adults – JAMA Intern Med

11 May, 2024 | 13:35h | UTC

Study Design and Population: The ORCA-V1 study was a double-blind, placebo-controlled randomized clinical trial conducted across five US clinical sites from July 2022 to February 2023. It enrolled 160 adults who used nicotine e-cigarettes daily and expressed a desire to quit, but were not current cigarette smokers. Participants were predominantly middle-aged (mean age 33.6 years), with a slight female majority (51.9%).

Main Findings: The trial assessed cytisinicline, a plant-based alkaloid, compared to placebo over a 12-week period with follow-up to 16 weeks. Results showed that cytisinicline significantly increased continuous abstinence from e-cigarette use during the last four weeks of treatment (31.8% vs 15.1% with placebo; odds ratio, 2.64; 95% CI, 1.06-7.10; P = .04). The effect was less pronounced but still present during the four weeks post-treatment (23.4% vs 13.2% with placebo; odds ratio, 2.00; 95% CI, 0.82-5.32; P = .15). The medication was well-tolerated, with only 3.8% of the cytisinicline group discontinuing due to adverse events.

Implications for Practice: Cytisinicline offers a promising pharmacotherapy option for adults seeking to quit vaping, demonstrating both efficacy and safety in this trial. Further research in larger populations and over longer periods is needed to confirm these findings and fully establish cytisinicline’s role in treating nicotine e-cigarette dependence.

 

Reference (link to abstract – $ for full-text):

Rigotti NA et al. (2024). Efficacy and Safety of Cytisinicline in Adult E-Cigarette Vaping Cessation: Findings from the ORCA-V1 Randomized Clinical Trial. JAMA Intern Med. Published online May 6, 2024. DOI: 10.1001/jamainternmed.2024.1313

 


RCT: Effects of combined time-restricted eating and high-intensity functional training on body composition and cardiometabolic health in women with obesity – PLOS One

7 May, 2024 | 15:28h | UTC

This randomized clinical trial investigated the effects of time-restricted eating (TRE) and high-intensity functional training (HIFT), both separately and in combination, on body composition and cardiometabolic health in inactive women with obesity. Sixty-four participants were assigned to three groups: TRE alone, HIFT alone, and both TRE and HIFT (TRE-HIFT). Over 12 weeks, the TRE-HIFT group showed the most significant improvements in waist and hip circumference, fat mass, total cholesterol, triglyceride levels, insulin sensitivity, and blood glucose levels compared to the other groups. Weight and BMI reductions were also more substantial in the TRE-HIFT group than in the HIFT-only group. Furthermore, while all groups exhibited improvements, those combining both interventions experienced more pronounced changes in cardiometabolic parameters, suggesting the potential of integrated lifestyle interventions for enhancing health outcomes in this population.

 

Reference (link to free full-text):

Ranya Ameur et al. (2024). Unlocking the power of synergy: High-intensity functional training and early time-restricted eating for transformative changes in body composition and cardiometabolic health in inactive women with obesity. PLOS ONE. DOI: https://doi.org/10.1371/journal.pone.0301369

 


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