Internal Medicine
2024 Update to the ACC/AHA Clinical Performance and Quality Measures for Adults With Heart Failure – J Am Coll Cardiol
14 Aug, 2024 | 12:26h | UTCIntroduction:
The American Heart Association (AHA) and American College of Cardiology (ACC) have released the 2024 update to the 2020 clinical performance and quality measures for adults with heart failure. This update aligns with the latest 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure and introduces new performance and quality measures to improve patient care.
Key Points:
1 – Performance Measures (PM):
– PM-1: Guideline-Directed Medical Therapy (GDMT) at Discharge – Initiate optimal GDMT in hospitalized heart failure patients before discharge.
– PM-2: Blood Pressure Control in HFpEF – Ensure optimal blood pressure control in patients with heart failure with preserved ejection fraction (HFpEF).
– PM-3: SGLT2 Inhibitor Use in HFrEF – Prescribe sodium-glucose cotransporter-2 inhibitors for patients with heart failure with reduced ejection fraction (HFrEF).
2 – Quality Measures (QM):
– QM-1: SGLT2 Inhibitor in HFmrEF or HFpEF – Recommend SGLT2 inhibitors for patients with mildly reduced or preserved ejection fraction.
– QM-2: Social Determinants of Health – Screen and document actions addressing social determinants of health for heart failure patients.
– QM-3: Pregnancy Counseling – Provide patient-centered counseling on contraception and pregnancy risks for individuals with cardiomyopathy.
– QM-4: Continuation of GDMT in HFimpEF – Continue GDMT in patients with heart failure with improved ejection fraction (HFimpEF).
– QM-5: Optimization of GDMT before TEER – Optimize GDMT before performing transcatheter edge-to-edge repair (TEER) for chronic secondary severe mitral regurgitation.
– QM-6: Monoclonal Protein Screening for Cardiac Amyloidosis – Ensure monoclonal protein screening in patients undergoing bone scintigraphy for suspected transthyretin cardiac amyloidosis.
3 – Emphasis on Multidisciplinary Care: The guidelines highlight the importance of addressing cardiovascular disease risks, social determinants of health, and providing comprehensive patient education, particularly concerning reproductive health in women with cardiomyopathy.
4 – Exclusions: The measures exclude patients after heart transplantation or left ventricular assist device placement and allow for patient-specific exclusions when treatment is not appropriate based on clinical evidence or patient preference.
5 – No Retired Measures: The update did not retire any measures from the 2020 set, reflecting their continued relevance.
Conclusion:
The 2024 update introduces critical new performance and quality measures that reflect the latest evidence in heart failure management. These measures aim to improve patient outcomes by emphasizing guideline-directed therapies, multidisciplinary care, and consideration of social and health determinants.
Guideline Reference:
RCT: Bisoprolol Does Not Reduce COPD Exacerbations in High-Risk Patients – JAMA
14 Aug, 2024 | 12:31h | UTCStudy Design and Population: The Bisoprolol in COPD Study (BICS) was a double-blind, placebo-controlled randomized clinical trial conducted across 76 sites in the UK, including both primary and secondary care clinics. The study enrolled 515 patients with chronic obstructive pulmonary disease (COPD) who had moderate to severe airflow obstruction and a history of at least two exacerbations in the past year. Participants were randomly assigned to receive either bisoprolol (n=261) or placebo (n=258) and were followed for one year.
Main Findings: The primary outcome, the number of COPD exacerbations requiring treatment with oral corticosteroids, antibiotics, or both, did not differ significantly between the bisoprolol group (mean exacerbations, 2.03 per year) and the placebo group (mean exacerbations, 2.01 per year). The adjusted incidence rate ratio was 0.97 (95% CI, 0.84-1.13; P = .72), indicating no significant reduction in exacerbations with bisoprolol. Additionally, the rates of serious adverse events were similar between the two groups.
Implications for Practice: The findings suggest that bisoprolol does not reduce exacerbations in COPD patients at high risk and should not be recommended for this purpose. This study underscores the need for continued research into effective interventions for preventing COPD exacerbations in high-risk populations.
New AHA Guidelines for Managing Elevated Blood Pressure in Acute Care Settings – Hypertension
13 Aug, 2024 | 13:13h | UTCIntroduction:
The American Heart Association (AHA) has released a scientific statement focusing on the management of elevated blood pressure (BP) in acute care settings. This guideline addresses the significant variation in practice due to a lack of robust evidence for managing BP in such environments, particularly in emergencies or when elevated BP is asymptomatic.
Key Points:
1 – Classification of Elevated BP: Elevated BP in acute care settings is categorized into asymptomatic elevated BP and hypertensive emergency, the latter requiring immediate treatment due to acute target-organ damage.
2 – Hypertensive Emergency: Immediate treatment is necessary for patients with BP >180/110–120 mm Hg and evidence of new or worsening target-organ damage, typically using intravenous antihypertensive medications in a closely monitored environment.
3 – Asymptomatic Elevated BP: In cases where elevated BP is present without symptoms or target-organ damage, the use of antihypertensive medications should be approached cautiously. Recent studies suggest potential harm from aggressive treatment, highlighting the importance of verifying BP readings and identifying reversible causes before intervention.
4 – Proper BP Measurement: Accurate BP measurement is crucial. The guidelines stress using recently calibrated devices and following correct measurement techniques to avoid unnecessary treatment due to erroneous readings.
5 – PRN Orders: The use of “as needed” (PRN) antihypertensive medications for asymptomatic elevated BP is discouraged due to the risks of overtreatment and variability in BP control, which can lead to adverse outcomes.
6 – Treatment Thresholds: The guidelines recommend a high threshold for initiating or intensifying antihypertensive treatment in asymptomatic patients, emphasizing the need for repeated measurements and assessment of underlying causes.
7 – Post-Discharge Care: It is crucial to maintain prehospital antihypertensive regimens and avoid intensification at discharge unless clearly indicated. Effective care coordination and patient education are vital for successful transitions from hospital to home care.
Conclusion:
These guidelines represent a significant step toward standardizing BP management in acute care settings. By focusing on accurate measurement, cautious treatment of asymptomatic elevated BP, and proper follow-up, clinicians can reduce unnecessary interventions and improve patient outcomes.
Guideline Reference: Bress, A.P., et al. (2024). “The Management of Elevated Blood Pressure in the Acute Care Setting: A Scientific Statement from the American Heart Association.” Hypertension, 81–e106.
RCT: Eliminating Fasting Before Contrast-Enhanced CT in Outpatients Reduces Nausea and Vomiting Without Increasing Acute Adverse Reactions – Insights Imaging
11 Aug, 2024 | 13:41h | UTCStudy Design and Population: This single-center, randomized clinical trial was conducted in Spain with 1,103 adult outpatients undergoing non-emergency contrast-enhanced CT scans. Patients were randomized into two groups: one group fasted for at least 6 hours (control), while the other group had no food restrictions (intervention). The primary aim was to assess whether eliminating fasting affects the incidence of acute adverse reactions (AARs), such as nausea and vomiting.
Main Findings: The study found no significant difference in the overall incidence of acute adverse reactions between the fasting and non-fasting groups (3.21% vs. 2.30%; p = 0.36). However, the non-fasting group had a significantly lower incidence of nausea and vomiting (0.92% vs. 2.86%; p = 0.02). Multivariate logistic regression identified fasting, age, allergies, neurological diseases, and contrast media concentration as independent risk factors for nausea and vomiting.
Implications for Practice: The findings suggest that the traditional practice of fasting before contrast-enhanced CT scans is unnecessary and may increase the risk of nausea and vomiting. Therefore, unrestricted food intake should be allowed for most contrast-enhanced CT exams, reserving fasting only for specific imaging procedures.
Meta-Analysis: Inhaled Antibiotics Offer Modest Reductions in Exacerbations and Quality of Life Gains in Bronchiectasis – CHEST
11 Aug, 2024 | 13:12h | UTCStudy Design and Population: This study is an updated systematic review and meta-analysis of 20 randomized controlled trials involving 3,468 adults with bronchiectasis, who were treated with inhaled antibiotics. The trials included in the analysis were selected based on criteria such as a minimum treatment duration of 4 weeks and involved patients diagnosed by CT imaging. The primary endpoint was exacerbation frequency, while secondary endpoints included severe exacerbations, bacterial load, symptoms, quality of life, and FEV1.
Main Findings: The meta-analysis found that inhaled antibiotics modestly reduced the proportion of patients experiencing exacerbations (risk ratio [RR], 0.85) and exacerbation frequency (RR, 0.78). Severe exacerbations were also decreased (RR, 0.48), and there was a slight increase in the time to the first exacerbation (hazard ratio [HR], 0.80). Additionally, quality of life showed modest improvements as measured by the Quality of Life Questionnaire-Bronchiectasis (mean difference, 2.51) and the St. George Respiratory Questionnaire (mean difference, -3.13). Bacterial load was consistently reduced, although FEV1 did not change meaningfully with treatment. The rate of adverse effects was similar to placebo (odds ratio [OR], 0.99), but antibiotic resistance appeared more likely to increase with treatment.
Implications for Practice: Inhaled antibiotics appear to be a beneficial treatment for adults with bronchiectasis, as they can reduce both exacerbation rates and severity while also improving quality of life. However, the increased risk of antibiotic resistance is a concern, indicating the need for careful patient selection and monitoring during treatment. These findings support the use of inhaled antibiotics in appropriate cases, particularly for those at high risk of exacerbations.
Systematic Review: Uncertain Impact of Vitamin D Supplementation During Pregnancy on Key Maternal and Neonatal Outcomes – Cochrane Database Syst Rev
11 Aug, 2024 | 12:42h | UTCStudy Design and Population: This Cochrane systematic review evaluates the effects of vitamin D supplementation alone or in combination with calcium and other vitamins/minerals during pregnancy. The analysis included 10 randomized controlled trials (RCTs) with a total of 2,313 pregnant women. The review excluded 20 studies from previous versions due to trustworthiness concerns and incorporated one new study.
Main Findings: The evidence regarding vitamin D supplementation alone was very uncertain for its impact on pre-eclampsia, gestational diabetes, preterm birth, and nephritic syndrome. There is low-certainty evidence suggesting that vitamin D may reduce the risk of severe postpartum hemorrhage and low birthweight, though the possibility of increased risk cannot be excluded. Supplementation with vitamin D plus calcium showed very uncertain effects on preterm birth and low birthweight, with no conclusive data on pre-eclampsia, gestational diabetes, or maternal adverse events. The combination of vitamin D, calcium, and other vitamins/minerals also yielded very uncertain evidence for all outcomes examined.
Implications for Practice: The current evidence does not provide strong support for routine vitamin D supplementation during pregnancy due to the low and very uncertain evidence on key outcomes. Further high-quality RCTs are needed to better understand the effects, particularly concerning maternal adverse events and neonatal health.
IDSA 2024 Guidelines for Managing Complicated Intra-abdominal Infections – Clin Infect Dis
10 Aug, 2024 | 22:10h | UTCIntroduction: The Infectious Diseases Society of America (IDSA) has updated its clinical practice guidelines for managing complicated intra-abdominal infections in adults, children, and pregnant individuals. The update focuses on risk assessment, diagnostic imaging, and microbiological evaluation, with recommendations grounded in systematic literature reviews and the GRADE approach for rating evidence.
Key Points:
1 – Risk Stratification:
– For adults with complicated intra-abdominal infections, the APACHE II score is recommended for risk stratification within 24 hours of hospital or ICU admission. The WSES Sepsis Severity Score is an acceptable alternative.
– No specific severity scoring system is recommended for pediatric patients.
2 – Diagnostic Imaging for Appendicitis:
– In non-pregnant adults, CT is suggested as the initial imaging modality for suspected acute appendicitis.
– For children, an abdominal ultrasound (US) is preferred initially, with MRI or CT recommended if the US is inconclusive.
– In pregnant individuals, US or MRI can be considered, with MRI suggested if initial US results are inconclusive.
3 – Imaging for Acute Cholecystitis and Cholangitis:
– For non-pregnant adults, US is recommended initially. If inconclusive, a CT scan is suggested.
– For pregnant individuals, US or MRI can be used, but the guidelines do not specify a preferred modality due to a knowledge gap.
4 – Blood Cultures:
– Blood cultures are recommended in adults and children with suspected intra-abdominal infections presenting with severe symptoms such as hypotension or tachypnea, especially when antibiotic-resistant organisms are a concern.
– Routine blood cultures are not recommended for patients without these risk factors.
5 – Intra-abdominal Fluid Cultures:
– In complicated intra-abdominal infections requiring source control procedures, obtaining intra-abdominal cultures is advised to guide antimicrobial therapy.
– In uncomplicated appendicitis cases, routine cultures are not recommended unless the patient is immunocompromised or complicated disease is suspected during surgery.
Conclusion: These guidelines provide evidence-based recommendations to improve the management of complicated intra-abdominal infections, emphasizing appropriate risk stratification, targeted diagnostic imaging, and the selective use of cultures to guide therapy.
Cluster RCT: AI-ECG Shows Potential to Reduce Door-to-Balloon Time and Cardiac Deaths in STEMI Patients – NEJM AI
10 Aug, 2024 | 21:57h | UTCStudy Design and Population: This open-label, cluster randomized controlled trial assessed the impact of AI-powered electrocardiogram (AI-ECG) on reducing treatment delays for ST-elevation myocardial infarction (STEMI). The study involved 43,234 patients, with an average age of 60 years, at Tri-Service General Hospital in Taiwan. Patients were randomized 1:1 into an intervention group (AI-ECG-assisted STEMI detection) or a control group receiving standard care.
Main Findings: AI-ECG significantly reduced the median door-to-balloon time for emergency department patients (82.0 vs. 96.0 minutes, P=0.002) and the ECG-to-balloon time across all settings (78.0 vs. 83.6 minutes, P=0.011). While the AI-ECG intervention did not significantly affect all-cause mortality or new-onset heart failure, it led to a notable reduction in cardiac death rates (85 vs. 116 cases; odds ratio, 0.73; P=0.029).
Implications for Practice: AI-ECG can expedite the critical time to treatment for STEMI patients, potentially reducing cardiac death. Although overall mortality remained unchanged, the reduction in cardiac deaths suggests that AI-ECG could be a valuable tool in emergency and inpatient settings to improve outcomes for STEMI patients.
Consensus Recommendations: Cardiovascular Risks in People With Narcolepsy – J Am Hear Assoc
10 Aug, 2024 | 21:48h | UTCIntroduction: The Journal of the American Heart Association recently published a consensus guideline by a panel of sleep and cardiology experts to address the heightened cardiovascular risks in individuals with narcolepsy. Given the increased prevalence of hypertension and cardiometabolic comorbidities in this population, the panel developed recommendations aimed at mitigating these risks.
Key Points:
1 – Increased Cardiovascular Risk in Narcolepsy:
– Individuals with narcolepsy, both Type 1 (NT1) and Type 2 (NT2), exhibit higher rates of cardiovascular and cardiometabolic diseases, such as hypertension, obesity, and diabetes, compared to the general population.
– The association of narcolepsy with conditions like obstructive sleep apnea (OSA) and restless legs syndrome further elevates cardiovascular risk.
2 – Monitoring and Early Detection:
– Clinicians should annually monitor blood pressure, weight, and waist circumference in patients with narcolepsy, even in the absence of existing cardiovascular disease.
– Screening for lipid levels and hemoglobin A1c is recommended, especially in patients with risk factors like hypertension, obesity, and diabetes.
3 – Lifestyle and Therapeutic Interventions:
– Patients should be educated about the link between narcolepsy and cardiovascular disease. Emphasis should be placed on maintaining optimal sleep duration, regular exercise, healthy eating, and reducing sodium intake.
– The American Heart Association’s “Life’s Essential 8” guidelines should be followed to enhance overall cardiovascular health.
4 – Medication Management:
– Narcolepsy medications, particularly stimulants and sodium oxybate, can increase cardiovascular risk. Clinicians should consider the patient’s cardiovascular profile when prescribing these treatments and explore alternatives with lower cardiovascular impact if necessary.
5 – Sodium Reduction:
– High sodium intake, from both diet and certain narcolepsy medications, is associated with increased blood pressure and cardiovascular disease. Patients should be advised to reduce sodium intake, and clinicians should consider prescribing lower-sodium alternatives when possible.
Conclusion: These expert consensus recommendations underscore the importance of proactive cardiovascular risk management in patients with narcolepsy. By implementing these guidelines, clinicians can help mitigate the long-term cardiovascular risks associated with this chronic sleep disorder.
Retrospective Study: Automated Multiorgan CT Markers Predict Diabetes and Cardiometabolic Comorbidities – Radiology
10 Aug, 2024 | 21:36h | UTCStudy Design and Population: This retrospective study analyzed data from 32,166 Korean adults (mean age, 45 years) who underwent health screenings, including fluorodeoxyglucose PET/CT scans, between 2012 and 2015. The study aimed to evaluate the predictive ability of automated CT-derived markers, such as visceral and subcutaneous fat, muscle area, bone density, liver fat, and aortic calcification, for diabetes and associated cardiometabolic conditions.
Main Findings: Visceral fat index showed the highest predictive performance for both prevalent and incident diabetes, with an AUC of 0.70 for men and 0.82 for women in cross-sectional analyses. Combining visceral fat, muscle area, liver fat, and aortic calcification improved prediction, yielding a C-index of 0.69 for men and 0.83 for women. Additionally, the study found that these CT markers were effective in identifying metabolic syndrome, fatty liver, coronary artery calcium scores >100, sarcopenia, and osteoporosis, with AUCs ranging from 0.80 to 0.95.
Implications for Practice: Automated CT-derived markers can effectively predict diabetes and multiple cardiometabolic comorbidities, surpassing traditional anthropometric measures. These findings suggest that integrating such automated assessments into routine clinical practice could enhance risk stratification and preventive care, particularly through opportunistic screening during routine CT scans.
Nested Case-Control Study: Sulfonamide Antibiotics and Cephalosporins Linked to Highest Risk of Serious Cutaneous Adverse Drug Reactions – JAMA
10 Aug, 2024 | 21:16h | UTCStudy Design and Population: This population-based, nested case-control study assessed the risk of serious cutaneous adverse drug reactions (cADRs) among older adults (66 years and above) in Ontario, Canada, who received oral antibiotics between 2002 and 2022. The study included 21,758 cases of emergency department visits or hospitalizations for serious cADRs, matched with 87,025 controls.
Main Findings: The study found that sulfonamide antibiotics (adjusted odds ratio [aOR], 2.9) and cephalosporins (aOR, 2.6) posed the highest risk of serious cADRs compared to macrolides. Nitrofurantoin, penicillins, and fluoroquinolones also showed elevated risks. Cephalosporins had the highest crude rate of cADRs (4.92 per 1,000 prescriptions).
Implications for Practice: The findings suggest that clinicians should consider the higher risks of serious cADRs associated with sulfonamide antibiotics and cephalosporins when prescribing antibiotics, opting for lower-risk alternatives when appropriate.
Erythritol Ingestion Increases Platelet Reactivity and Thrombosis Potential in Healthy Adults – Arterioscler Thromb Vasc Biol
10 Aug, 2024 | 21:11h | UTCStudy Design and Population: This interventional study evaluated the effects of erythritol versus glucose on platelet reactivity and thrombosis potential in 20 healthy volunteers, with 10 participants in each group. Researchers measured erythritol plasma levels and assessed platelet function through aggregometry and granule marker analysis both before and after ingestion of 30 g of erythritol or glucose.
Main Findings: Erythritol ingestion resulted in a more than 1000-fold increase in plasma erythritol concentration and significantly enhanced stimulus-dependent platelet aggregation and release of serotonin and CXCL4, markers of platelet activation. In contrast, glucose ingestion did not significantly alter platelet reactivity or granule marker release, highlighting erythritol’s unique pro-thrombotic effects.
Implications for Practice: These findings raise concerns regarding the safety of erythritol as a non-nutritive sweetener, particularly its potential to enhance thrombosis risk. The results suggest a need to reevaluate erythritol’s safety status and consider its impact on cardiovascular health in regulatory guidelines.
Phase 3 RCT: Butantan-DV Dengue Vaccine is Safe and Shows 67.3% Efficacy Over 3.7 Years in Participants Aged 2–59 Years – Lancet Infect Dis
10 Aug, 2024 | 20:23h | UTCStudy Design and Population: This double-blind, randomized, placebo-controlled, phase 3 trial conducted in Brazil evaluated the efficacy and safety of the Butantan-dengue vaccine (Butantan-DV) in 16,235 healthy participants aged 2–59 years. Participants, who had not previously received a dengue vaccine, were randomly assigned to receive either a single dose of Butantan-DV or a placebo and were followed up for an average of 3.7 years.
Main Findings: The study found that Butantan-DV demonstrated 67.3% efficacy against virologically confirmed dengue (VCD) caused by any dengue virus serotype, with no cases of VCD caused by DENV-3 or DENV-4. The proportions of serious adverse events were similar between the vaccine and placebo groups, indicating that the vaccine was generally well tolerated.
Implications for Practice: The results support the potential of the Butantan-DV vaccine as an effective intervention for preventing symptomatic dengue, particularly from DENV-1 and DENV-2, across a broad age range regardless of dengue serostatus. Continued development and monitoring are warranted to confirm long-term efficacy and safety.
IDSA 2024 Guidelines for Treatment of Antimicrobial-Resistant Gram-Negative Infections – Clin Infect Dis
10 Aug, 2024 | 20:16h | UTCIntroduction:
The Infectious Diseases Society of America (IDSA) has released updated guidelines in 2024 addressing the treatment of infections caused by antimicrobial-resistant (AMR) Gram-negative bacteria. These guidelines cover pathogens including extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E), AmpC β-lactamase-producing Enterobacterales (AmpC-E), carbapenem-resistant Enterobacterales (CRE), difficult-to-treat Pseudomonas aeruginosa (DTR P. aeruginosa), carbapenem-resistant Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia.
Key Points:
1 – ESBL-E Infections:
– Preferred treatment for uncomplicated cystitis includes nitrofurantoin and TMP-SMX. Fluoroquinolones and carbapenems are alternatives but should be reserved to prevent resistance.
– For pyelonephritis or complicated urinary tract infections (cUTI), TMP-SMX, ciprofloxacin, or levofloxacin are preferred. Carbapenems are recommended when resistance precludes other options.
2 – AmpC-E Infections:
– Cefepime is suggested for treating infections caused by organisms at moderate risk of significant AmpC production (e.g., Enterobacter cloacae complex, Klebsiella aerogenes, and Citrobacter freundii).
– The use of cephamycins (e.g., cefoxitin, cefotetan) for treating ESBL-E infections is not recommended due to insufficient clinical outcome data.
3 – CRE Infections:
– Acknowledgement of increased prevalence of metallo-beta-lactamase (MBL)-producing CRE in the U.S.
– The combination of ceftazidime-avibactam and aztreonam is suggested for MBL-producing CRE, with updated dosing recommendations provided.
4 – DTR Pseudomonas aeruginosa:
– Traditional β-lactams (e.g., cefepime) with high-dose extended-infusion therapy are recommended.
– Tobramycin or amikacin, administered once daily, are alternatives for pyelonephritis or cUTI.
5 – CRAB and Stenotrophomonas maltophilia Infections:
– Sulbactam-durlobactam with meropenem or imipenem-cilastatin is the preferred treatment for CRAB.
– The order of preference for agents treating S. maltophilia includes cefiderocol, ceftazidime-avibactam, and aztreonam, among others.
Conclusion:
The 2024 IDSA guidelines provide critical updates on managing AMR Gram-negative infections, emphasizing the importance of selecting the appropriate antibiotic based on susceptibility, resistance mechanisms, and patient-specific factors. These guidelines are essential for optimizing treatment outcomes in the face of increasing antimicrobial resistance.
Reference:
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.