All Posts
Cohort Studies: Metformin During Early Pregnancy or Spermatogenesis is Safe Regarding Congenital Malformation Risks – Ann Intern Med
10 Aug, 2024 | 20:05h | UTCStudy Design and Population: Two observational cohort studies assessed the safety of metformin, focusing on early pregnancy and paternal use during spermatogenesis. The first study involved 12,489 pregnant women with pregestational type 2 diabetes, comparing those on insulin monotherapy to those on insulin plus metformin. The second study analyzed 383,851 live births in Israel, examining the impact of paternal metformin use during spermatogenesis on congenital malformations in newborns.
Main Findings: The first study found no significant increase in the risk of nonlive births when continuing metformin in early pregnancy compared to switching to insulin monotherapy. The risk of congenital malformations was also comparable between the two groups. The second study showed that paternal metformin use in monotherapy did not raise the risk of major congenital malformations, though a slight risk increase was observed with metformin in polytherapy, potentially due to underlying cardiometabolic conditions.
Implications for Practice: These findings suggest that metformin use, either during early pregnancy or spermatogenesis, poses minimal risk for congenital malformations. However, clinicians should consider the overall cardiometabolic profile and diabetes management when prescribing metformin, especially in combination with other antidiabetic medications.
References:
RCT: Dapagliflozin Does Not Improve Outcomes in Critically Ill Patients With Acute Organ Dysfunction – JAMA
10 Aug, 2024 | 19:58h | UTCStudy Design and Population: This multicenter, open-label, randomized clinical trial conducted across 22 ICUs in Brazil evaluated the effect of adding dapagliflozin to standard care in 507 critically ill patients with at least one acute organ dysfunction (respiratory, cardiovascular, or kidney). The study took place between November 2022 and September 2023, with participants randomly assigned to either 10 mg of dapagliflozin plus standard care or standard care alone for up to 14 days or until ICU discharge.
Main Findings: The primary outcome, a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay, showed no significant difference between the dapagliflozin and control groups (win ratio, 1.01; 95% CI, 0.90 to 1.13; P = .89). Secondary outcomes also did not demonstrate significant benefits, although dapagliflozin had a slightly higher probability of reducing the need for kidney replacement therapy.
Implications for Practice: The addition of dapagliflozin to standard care in critically ill patients with acute organ dysfunction did not improve overall clinical outcomes. Although the study did not find significant benefits, the wide confidence intervals suggest that further research could be warranted to explore potential effects more definitively.
RCT: Tirzepatide Significantly Improves MASH Resolution Without Worsening Fibrosis Over 52 Weeks – N Engl J Med
10 Aug, 2024 | 19:53h | UTCStudy Design and Population: This phase 2, multicenter, double-blind, randomized, placebo-controlled trial evaluated the efficacy and safety of tirzepatide in 190 participants with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH) and moderate to severe liver fibrosis (stage F2 or F3). Participants were assigned to receive subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo weekly for 52 weeks.
Main Findings: Tirzepatide significantly improved MASH resolution without worsening fibrosis compared to placebo. Resolution rates were 44% for 5 mg, 56% for 10 mg, and 62% for 15 mg, versus 10% for placebo. Improvement in fibrosis stage without worsening MASH was also higher in tirzepatide groups (51-55%) than in the placebo group (30%). The most common adverse events were mild to moderate gastrointestinal symptoms.
Implications for Practice: Tirzepatide shows promise as a treatment for MASH with moderate to severe fibrosis, significantly improving disease resolution without worsening fibrosis. However, further research with larger and longer trials is needed to confirm these findings and evaluate long-term safety.
Phase 2 Trial: Survodutide Improves MASH Without Worsening Fibrosis, But Increases GI Side Effects – N Engl J Med
10 Aug, 2024 | 19:47h | UTCStudy Design and Population: This 48-week, phase 2 randomized trial evaluated the efficacy and safety of survodutide, a dual agonist of the glucagon and GLP-1 receptors, in 293 adults with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis (F1-F3 stages). Participants were randomized to receive weekly injections of survodutide (2.4, 4.8, or 6.0 mg) or placebo.
Main Findings: Survodutide significantly improved MASH without worsening fibrosis compared to placebo, with 47% to 62% of participants in the survodutide groups achieving histologic improvement versus 14% in the placebo group. A reduction in liver fat content by at least 30% was observed in 57% to 67% of participants receiving survodutide, compared to 14% in the placebo group. However, adverse events such as nausea, diarrhea, and vomiting were more common with survodutide.
Implications for Practice: The findings suggest that survodutide could be a promising treatment for MASH, with potential benefits for liver histology and fat content. However, the increased gastrointestinal side effects warrant careful consideration in future phase 3 trials to better evaluate the drug’s safety profile and long-term efficacy.
Randomized Trials: Tirzepatide Reduces Apnea-Hypopnea Index and Body Weight in Patients with Obstructive Sleep Apnea and Obesity – N Engl J Med
10 Aug, 2024 | 19:38h | UTCStudy Design and Population: This study comprises two phase 3, double-blind, randomized trials involving adults with moderate-to-severe obstructive sleep apnea (OSA) and obesity. Participants were either using or not using positive airway pressure (PAP) therapy at baseline and received tirzepatide or placebo over 52 weeks.
Main Findings: Tirzepatide significantly reduced the apnea-hypopnea index (AHI) by 20-24 events per hour compared to placebo and also lowered body weight, hypoxic burden, and systolic blood pressure.
Implications for Practice: Tirzepatide offers a promising treatment for reducing OSA severity and associated obesity-related complications, but further research is needed to confirm long-term benefits.
New Guidelines Recommend Against Routine Vitamin D Testing and Treatment for Healthy Adults – J Clin Endocrinol Metab
4 Aug, 2024 | 19:19h | UTCIntroduction: The Endocrine Society has developed new clinical practice guidelines focused on the use of vitamin D for the prevention of various diseases. These guidelines were created by a multidisciplinary panel, including experts in adult and pediatric endocrinology, internal medicine, obstetrics and gynecology, nutrition, and epidemiology.
Key Points:
1 – Empiric Vitamin D Supplementation in Children and Adolescents:
– Recommended to prevent nutritional rickets.
– May lower the risk of respiratory tract infections.
– Dosage in trials ranged from 300 to 2000 IU daily, with an average of about 1200 IU per day.
2 – Empiric Vitamin D Supplementation or Testing in Adults Under 75:
– Not recommended for generally healthy adults without specific indications.
3 – Empiric Vitamin D Supplementation in Adults Over 75:
– Suggested due to its potential to lower the risk of mortality.
– Treatment should be empirical, no testing recommended if there are no established indications for testing (e.g., hypocalcemia).
– Recommended daily rather than intermittent high doses. Dosage in clinical trials ranged from 400 to 3333 IU daily equivalent.
4 – Vitamin D Supplementation During Pregnancy:
– Suggested to lower the risk of preeclampsia, intrauterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality.
– Empiric supplementation recommended without routine 25(OH)D testing unless there are established indications for testing.
– Dosages in trials ranged from 600 to 5000 IU daily equivalent, with an average of about 2500 IU per day.
5 – Vitamin D and High-Risk Prediabetes:
– Suggested to reduce the progression to diabetes.
– In clinical trials, vitamin D dosages ranged from 842 to 7543 IU daily. The estimated weighted average was approximately 3500 IU per day.
6 – Routine 25(OH)D Testing:
– Not recommended for the general population, including those with obesity or dark complexion.
– No clear evidence defining optimal target levels for disease prevention.
Conclusion: These guidelines emphasize the importance of targeted vitamin D supplementation for specific age groups and conditions, while advising against routine testing for vitamin D levels in the general population. Empiric supplementation is considered beneficial, particularly in children, pregnant women, and older adults, and is feasible, cost-effective, and generally acceptable.
RCT: Intravenous Amino Acids Reduce AKI Incidence in Cardiac Surgery Patients – N Engl J Med
3 Aug, 2024 | 19:12h | UTCStudy Design and Population: In this multinational, double-blind, randomized clinical trial, 3511 adult patients scheduled for cardiac surgery with cardiopulmonary bypass were recruited from 22 centers across three countries. Patients were randomly assigned to receive an intravenous infusion of either a balanced mixture of amino acids (2 g/kg/day) or a placebo (Ringer’s solution) for up to three days.
Main Findings: The primary outcome, occurrence of acute kidney injury (AKI), was significantly lower in the amino acid group (26.9%) compared to the placebo group (31.7%) with a relative risk of 0.85 (95% CI, 0.77 to 0.94; P=0.002). The incidence of severe AKI (stage 3) was also reduced in the amino acid group (1.6% vs. 3.0%; relative risk, 0.56; 95% CI, 0.35 to 0.87). There were no substantial differences between the groups regarding secondary outcomes such as the use and duration of kidney-replacement therapy or all-cause 30-day mortality.
Implications for Practice: The infusion of amino acids in adult patients undergoing cardiac surgery appears to reduce the incidence of AKI, indicating a potential protective renal effect. However, this intervention did not significantly impact other secondary outcomes, including mortality and the use of kidney-replacement therapy. These findings suggest that amino acids could be considered as a strategy to mitigate AKI risk in this patient population, although further research is needed to explore long-term benefits and other clinical outcomes.
RCT: Liberal vs. Restrictive Transfusion Strategy Shows No Significant Difference in Neurologic Outcomes for Traumatic Brain Injury Patients – N Engl J Med
3 Aug, 2024 | 19:06h | UTCStudy Design and Population: This randomized clinical trial evaluated the effects of liberal versus restrictive red cell transfusion strategies in 742 adults with moderate to severe traumatic brain injury (TBI) and anemia. Participants were randomized to either a liberal transfusion strategy (initiated at hemoglobin ≤10 g/dL) or a restrictive strategy (initiated at hemoglobin ≤7 g/dL). The primary outcome was an unfavorable neurologic outcome at 6 months, assessed using the Glasgow Outcome Scale–Extended.
Main Findings: The study found that 68.4% of patients in the liberal-strategy group and 73.5% in the restrictive-strategy group experienced an unfavorable outcome (adjusted absolute difference of 5.4 percentage points; 95% CI, −2.9 to 13.7). No significant difference in mortality or depression was observed between the two groups. Although some functional independence and quality of life measures were better in the liberal group among survivors, venous thromboembolic events and acute respiratory distress syndrome rates were comparable.
Implications for Practice: The findings indicate that a liberal transfusion strategy does not significantly improve neurologic outcomes at 6 months in critically ill TBI patients compared to a restrictive strategy. Clinicians may consider maintaining a restrictive transfusion strategy, given the similar outcomes and potential for fewer transfusions. Further research is needed to explore specific subgroups that might benefit from different transfusion strategies.
RCT: Tenecteplase Reduces Disability but Not Mortality in Ischemic Stroke 4.5 to 24 Hours Post-Onset – N Engl J Med
3 Aug, 2024 | 19:03h | UTCStudy Design and Population: This randomized clinical trial was conducted in China to assess the efficacy and safety of tenecteplase in patients with ischemic stroke caused by large-vessel occlusion. The study included 516 patients who were randomly assigned to receive either tenecteplase (264 patients) or standard medical treatment (252 patients) within 4.5 to 24 hours after stroke onset. All patients had salvageable brain tissue confirmed by perfusion imaging and did not have access to endovascular thrombectomy.
Main Findings: The primary outcome, absence of disability (modified Rankin scale score of 0 or 1) at 90 days, was achieved by 33.0% of patients in the tenecteplase group compared to 24.2% in the standard treatment group (relative rate, 1.37; 95% CI, 1.04 to 1.81; P=0.03). Mortality at 90 days was similar between the two groups (13.3% for tenecteplase vs. 13.1% for standard treatment). Symptomatic intracranial hemorrhage within 36 hours occurred in 3.0% of tenecteplase-treated patients compared to 0.8% of those receiving standard treatment.
Implications for Practice: The study suggests that tenecteplase administered 4.5 to 24 hours post-stroke onset can reduce disability in patients with large-vessel occlusion who do not have access to endovascular thrombectomy. However, the increased risk of symptomatic intracranial hemorrhage warrants cautious consideration. Further research may be needed to optimize patient selection and timing of administration to balance benefits and risks.
RCT: Reteplase More Likely to Achieve Excellent Functional Outcome Than Alteplase in Acute Ischemic Stroke – N Engl J Med
3 Aug, 2024 | 19:00h | UTCStudy Design and Population: This randomized clinical trial compared the efficacy and safety of reteplase versus alteplase in patients with acute ischemic stroke. The study involved 1,412 patients who presented within 4.5 hours of symptom onset. Patients were randomly assigned in a 1:1 ratio to receive either intravenous reteplase or intravenous alteplase.
Main Findings: The primary efficacy outcome, an excellent functional outcome (modified Rankin scale score of 0 or 1) at 90 days, was achieved in 79.5% of the reteplase group compared to 70.4% of the alteplase group (risk ratio, 1.13; 95% CI, 1.05 to 1.21; P<0.001 for noninferiority and P=0.002 for superiority). The primary safety outcome, symptomatic intracranial hemorrhage within 36 hours, was similar between groups (2.4% for reteplase vs. 2.0% for alteplase; risk ratio, 1.21; 95% CI, 0.54 to 2.75). However, reteplase was associated with a higher incidence of any intracranial hemorrhage at 90 days (7.7% vs. 4.9%; risk ratio, 1.59; 95% CI, 1.00 to 2.51) and more adverse events (91.6% vs. 82.4%; risk ratio, 1.11; 95% CI, 1.03 to 1.20).
Implications for Practice: Reteplase shows superior efficacy in achieving excellent functional outcomes compared to alteplase in acute ischemic stroke, making it a viable alternative thrombolytic agent. However, the higher risk of intracranial hemorrhage and adverse events necessitates careful patient selection and monitoring. Further research may be needed to refine dosage and administration protocols to mitigate these risks.
RCT: Pantoprazole Reduces GI Bleeding in Mechanically Ventilated ICU Patients – N Engl J Med
3 Aug, 2024 | 18:57h | UTCStudy Design and Population: This international, randomized, double-blind trial involved 4,821 critically ill adults undergoing invasive mechanical ventilation across 68 intensive care units (ICUs). Participants were assigned to receive either intravenous pantoprazole (40 mg daily) or a matching placebo. The primary efficacy outcome was the incidence of clinically significant upper gastrointestinal bleeding within 90 days, and the primary safety outcome was mortality from any cause within the same period.
Main Findings: The trial found that upper gastrointestinal bleeding occurred in 1.0% of patients treated with pantoprazole compared to 3.5% in the placebo group (hazard ratio, 0.30; 95% CI, 0.19 to 0.47; P<0.001). Mortality at 90 days was 29.1% in the pantoprazole group and 30.9% in the placebo group, showing no significant difference (hazard ratio, 0.94; 95% CI, 0.85 to 1.04; P=0.25). There were no significant differences in the rates of ventilator-associated pneumonia or Clostridioides difficile infection between the groups.
Implications for Practice: The study demonstrates that pantoprazole significantly reduces the risk of upper gastrointestinal bleeding in critically ill patients on mechanical ventilation without affecting overall mortality. This suggests that pantoprazole can be considered a safe and effective option for stress ulcer prophylaxis in this high-risk population, potentially improving patient outcomes in the ICU.
Meta-Analysis: Effects of extracorporeal CO2 removal on gas exchange and ventilator settings in critically ill adults – Crit Care
27 May, 2024 | 20:28h | UTCSummary: 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):
Randomized Controlled Trial: Mixed results with Andexanet Alfa for Factor Xa inhibitor-associated acute intracerebral hemorrhage – N Engl J Med
27 May, 2024 | 20:26h | UTCStudy Design and Population: This randomized controlled trial involved 530 patients with acute intracerebral hemorrhage who had taken factor Xa inhibitors within 15 hours before the event. They were randomly assigned to receive either andexanet alfa or usual care.
Main Findings: Hemostatic efficacy was achieved in 67% of patients receiving andexanet compared to 53.1% receiving usual care. Andexanet significantly reduced anti-factor Xa activity by 94.5%, compared to 26.9% with usual care. However, thrombotic events were more frequent in the andexanet group, including ischemic stroke.
Implications for Practice: Andexanet alfa is effective in controlling hematoma expansion in patients with factor Xa inhibitor-associated intracerebral hemorrhage but has an increased risk of thrombotic events. Further research is needed to balance efficacy and safety.
Reference (link to abstract – $ for full-text):
Randomized Clinical Trial: Aficamten improves peak oxygen uptake in symptomatic obstructive hypertrophic cardiomyopathy – N Engl J Med
27 May, 2024 | 20:24h | UTCStudy 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):
AAN updated practice guidelines for epilepsy and pregnancy – Neurology
27 May, 2024 | 20:23h | UTCIntroduction:
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:
- 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.
- 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.
- Monitoring and Adjusting ASM Levels: ASM levels should be monitored throughout pregnancy, and doses should be adjusted based on serum levels and seizure control.
- 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.
- 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.
- 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.
- 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):
Subgroup Analysis Insights: Apixaban vs. aspirin in subclinical atrial fibrillation based on CHA2DS2-VASc score – J Am Coll Cardiol
27 May, 2024 | 20:21h | UTCStudy 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):
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 | UTCStudy 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):
Randomized Clinical Trial: Dequalinium chloride demonstrates noninferiority to metronidazole in treating bacterial vaginosis – JAMA Netw Open
25 May, 2024 | 19:55h | UTCThis 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):
Cohort Study: GLP1 receptor agonist use not associated with significant increase in thyroid cancer risk – The BMJ
25 May, 2024 | 19:51h | UTCA 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):
Cohort Study: Prenatal opioid exposure linked to modest increase in neuropsychiatric disorders – The BMJ
25 May, 2024 | 19:50h | UTCThis nationwide birth cohort study from South Korea investigated the impact of prenatal opioid exposure on the risk of neuropsychiatric disorders among children. The study followed 3,128,571 infants born between 2010 and 2017 until the end of 2020. Researchers found that infants exposed to opioids prenatally showed a slightly increased risk of developing neuropsychiatric disorders, including mood disorders, attention deficit hyperactivity disorder, and intellectual disability. The increased risk was more pronounced with higher opioid doses, longer duration of use, and exposure during the first trimester of pregnancy. However, this association was not significant in sibling comparison cohorts, indicating a modest overall clinical impact. The study emphasizes the need for cautious interpretation due to its observational design and the specific conditions under which risk increases.
Reference (link to free full-text):
APA workgroup update maintains skepticism on pharmacogenomic tools for depression – Am J Psychiatry
25 May, 2024 | 19:47h | UTCA 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)
Single-Arm Study: Evaluation of transcatheter aortic valve implantation in patients with high-risk symptomatic native aortic regurgitation – The Lancet
25 May, 2024 | 19:45h | UTCThis article discusses the ALIGN-AR study, a prospective, multicenter, single-arm trial conducted across 20 US sites. The study enrolled 180 high-risk patients suffering from moderate-to-severe or severe symptomatic aortic regurgitation, who were treated with the Trilogy transcatheter heart valve. The average age of participants was 75.5 years, with a roughly equal gender distribution among the 180 participants. The primary safety endpoint of the study was assessed against a prespecified performance goal of 40.5%, with results showing a 27% event rate, which was considered non-inferior (p<0.0001). Additionally, the primary efficacy endpoint, 1-year all-cause mortality, was 7.8%, significantly below the performance goal of 25%, also demonstrating non-inferiority (p<0.0001). The study reported a 95% technical success rate with adverse events such as new pacemaker implantation occurring in 24% of the patients. These findings suggest that the Trilogy transcatheter heart valve is a viable and effective option for high-risk patients, achieving favorable short-term clinical and hemodynamic outcomes. Further follow-up is necessary to determine long-term results and effects on left ventricular remodeling.
Reference (link to abstract – $ for full-text):
Post hoc analysis: Laparoscopic spleen-preserving hilar lymphadenectomy may improve 5-year survival in advanced proximal gastric cancer without greater curvature invasion – JAMA Surg
25 May, 2024 | 19:43h | UTCThis study presents the results of a post hoc secondary analysis from the Fuges-02 randomized clinical trial, investigating the effects of laparoscopic total gastrectomy (LTG) with and without spleen-preserving splenic hilar lymphadenectomy (LSPSHL) in 536 patients with resectable advanced proximal gastric cancer (APGC) lacking greater curvature invasion. Conducted from January 2015 to October 2018 with a minimum follow-up of five years, the study reported a significantly improved 5-year disease-free survival (DFS) rate of 63.9% in the LTG with LSPSHL group compared to 55.1% in the LTG alone group. The overall survival (OS) also favored the LSPSHL group at 66.2% versus 57.4% in the LTG group. Furthermore, the recurrence rate was lower in the LSPSHL group, with a notable reduction in recurrence at the No. 10 lymph node area, indicating a protective benefit from the addition of LSPSHL. The findings suggest a potential therapeutic advantage of incorporating LSPSHL in surgical protocols for APGC without greater curvature invasion, warranting further investigation through multicenter studies.
Reference (link to abstract – $ for full-text):
Phase 1-2 Study: Safety and efficacy of EDIT-101 CRISPR-Cas9 treatment for CEP290-associated retinal degeneration – N Engl J Med
25 May, 2024 | 19:42h | UTCThis study evaluates the safety and effectiveness of EDIT-101, a CRISPR-Cas9 gene-editing therapy, in treating inherited retinal degeneration caused by CEP290 IVS26 variants. Conducted as a phase 1-2, open-label, single-ascending-dose trial, it involved 14 participants (12 adults aged 17-63 and 2 children aged 9 and 14) who received subretinal injections of EDIT-101. Treatment doses varied, with two participants at a low dose, seven at an intermediate dose, and five at a high dose. The primary safety assessment showed no serious adverse events or dose-limiting toxic effects. Notably, 64% of participants exhibited significant improvements in visual acuity, retinal sensitivity to red light, or mobility. Additionally, improvements in vision-related quality of life were documented in six participants. These promising results suggest that EDIT-101 is safe and potentially effective, warranting further investigation into CRISPR-Cas9 gene therapy for similar genetic retinal conditions.
Commentary on X:
Original Article: Gene Editing for CEP290-Associated Retinal Degeneration (BRILLIANCE) https://t.co/LgSs2RGBZv #ARVO2024 @ARVOinfo pic.twitter.com/WztX2OvzXM
— NEJM (@NEJM) May 7, 2024
Reference (link to abstract – $ for full-text):
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