Internal Medicine

RCT: Nonstandard Arm Positions Overestimate Blood Pressure Readings in Adults

12 Oct, 2024 | 22:55h | UTC

Background: Accurate blood pressure (BP) measurement is crucial for the diagnosis and management of hypertension, a leading cause of cardiovascular disease and mortality worldwide. Guidelines recommend measuring BP with the arm supported on a desk at heart level. However, in clinical practice, nonstandard arm positions—such as resting the arm on the lap or having it unsupported at the side—are commonly used, potentially leading to inaccurate readings.

Objective: To determine the effect of commonly used nonstandard arm positions on BP measurements compared to the standard, recommended position.

Methods: In a crossover randomized clinical trial from August 2022 to June 2023, 133 adults aged 18 to 80 years were recruited. Participants were randomly assigned to receive sets of triplicate BP measurements with the arm in three positions: (1) supported on a desk with the midcuff at heart level (desk 1; reference), (2) hand supported on the lap (lap), and (3) arm unsupported at the side (side). To account for intrinsic BP variability, all participants underwent a fourth set of BP measurements with the arm supported on a desk (desk 2). The primary outcomes were the difference in differences in mean systolic BP (SBP) and diastolic BP (DBP) between the reference BP (desk 1) and the two nonstandard arm positions (lap and side).

Results: Among 133 participants (mean age 57 years; 53% female), 36% had SBP ≥130 mm Hg, and 41% had a body mass index ≥30 kg/m². Compared to the reference position, the lap and side positions resulted in significantly higher BP readings. The difference in differences for the lap position was an increase in SBP of 3.9 mm Hg (95% CI, 2.5-5.2) and DBP of 4.0 mm Hg (95% CI, 3.1-5.0). For the side position, the increases were SBP 6.5 mm Hg (95% CI, 5.1-7.9) and DBP 4.4 mm Hg (95% CI, 3.4-5.4). These patterns were consistent across subgroups.

Conclusions: Commonly used nonstandard arm positions during BP measurements, such as resting the arm on the lap or having it unsupported at the side, significantly overestimate BP readings compared to the standard recommended position. This overestimation may lead to misdiagnosis and overestimation of hypertension.

Implications for Practice: Clinicians should adhere to guideline-recommended arm positioning during BP measurements to ensure accurate readings. Proper arm support with the midcuff at heart level is necessary to avoid overestimation of BP, which can result in unnecessary follow-up and overtreatment due to hypertension overdiagnosis.

Study Strengths and Limitations: Strengths include the randomized crossover design ideal for studying BP differences, a larger sample size than previous studies, and focus on arm positions commonly used in clinical practice with an automated BP device. Limitations include unequal randomization due to the randomization function used, small sample sizes in some subgroups, and uncertain generalizability to other settings or devices.

Future Research: Further studies are needed to investigate strategies to improve adherence to guideline-recommended arm positions in clinical practice, assess the impact of educational interventions on BP measurement accuracy, and explore the effects of arm position on BP readings using different devices or in diverse populations.

Reference: Liu H., et al. (2024). Arm Position and Blood Pressure Readings: The ARMS Crossover Randomized Clinical Trial. JAMA Internal Medicine. DOI: http://doi.org/10.1001/jamainternmed.2024.5213

 

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Review: Management of Atrial Fibrillation in Older Adults

12 Oct, 2024 | 19:52h | UTC

Introduction: Atrial fibrillation (AF) predominantly affects adults over 65 years old and often coexists with multiple chronic conditions, polypharmacy, and geriatric syndromes such as frailty. Despite this, most randomized controlled trials and guidelines do not tailor recommendations specifically for older adults with these complexities. This review addresses the gap by synthesizing evidence and applying aging science principles to AF management, aiming to provide a framework that prioritizes patients’ goals across the spectrum of older adults—from fit individuals to those who are frail or at the end of life.

Key Recommendations:

1. Individualized Care Approach: Clinicians should tailor AF management by considering patients’ comorbidities, frailty, and personal health goals. Tools like the Clinical Frailty Scale and comprehensive geriatric assessment can aid in assessing fitness and frailty.
2. Screening for AF: Systematic population-level screening for AF in older adults has not conclusively shown a reduction in stroke incidence. Decisions regarding screening should be individualized, weighing the potential benefits and burdens.
3. Lifestyle Interventions: For functional older adults, lifestyle modifications such as weight loss, moderate physical activity, blood pressure control, and alcohol avoidance are recommended to prevent and manage AF.
4. Symptom Management: Use validated patient-reported outcome measures to assess and manage AF symptoms effectively, aligning treatment with patients’ experiences and quality of life goals.
5. Rate and Rhythm Control:
   • Fit Older Adults: Early rhythm control is preferred, with catheter ablation showing superiority over anti-arrhythmic drugs in maintaining sinus rhythm and improving quality of life.
   • Multimorbid/Frail Older Adults: Treatment should be individualized, balancing the risks and benefits of anti-arrhythmic drugs versus catheter ablation.
   • Heart Failure Coexistence: Catheter ablation is recommended over medical therapy for patients with AF and heart failure with reduced ejection fraction.
6. Anticoagulation Therapy:
   • General Recommendation: Direct oral anticoagulants (DOACs) are preferred over warfarin due to similar efficacy and lower bleeding risk.
   • Multimorbid/Frail Older Adults: Apixaban is favored for its lower bleeding risk. Decisions should consider life expectancy and patient preferences.
   • End-of-Life Care: De-escalation of anticoagulation may be appropriate when risks outweigh benefits or when it aligns with the patient’s comfort-focused goals.
7. Left Atrial Appendage Closure (LAAC):
   • Indications: LAAC is considered for patients with contraindications to long-term anticoagulation.
   • Considerations: Procedural risks should be weighed against potential benefits, especially in frail older adults.

Conclusion: Implementing an individualized, goal-directed approach to AF management in older adults can enhance patient care by aligning treatments with patients’ health priorities and improving clinical outcomes. Recognizing the heterogeneity among older adults with AF, clinicians should adopt strategies that consider fitness, frailty, comorbidities, and patient preferences to optimize care across the aging spectrum.

Reference: Parks AL, Frankel DS, Kim DH, et al. (2024). Management of atrial fibrillation in older adults. BMJ. DOI: http://doi.org/10.1136/bmj-2023-076246

 

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Management of Ascites in Cirrhosis: Key Recommendations from the British Society of Gastroenterology Guidelines

12 Oct, 2024 | 18:23h | UTC

Introduction: Ascites, the pathological accumulation of fluid within the peritoneal cavity, is a common and serious complication of cirrhosis, indicating advanced liver disease and portending increased morbidity and mortality. Recognizing the need for updated clinical guidance, the British Society of Gastroenterology (BSG), in collaboration with the British Association for the Study of the Liver (BASL), has issued comprehensive guidelines. These aim to standardize the diagnosis and management of ascites in cirrhotic patients, incorporating recent advances to optimize patient outcomes.

Key Recommendations:

1. Diagnostic Paracentesis: It is strongly recommended that all patients with new-onset ascites undergo diagnostic paracentesis to measure total protein concentration and calculate the serum-ascites albumin gradient (SAAG). (Quality of evidence: moderate; Recommendation: strong)
2. Spontaneous Bacterial Peritonitis (SBP): Prompt diagnostic paracentesis should be performed in hospitalized patients with ascites, especially those with gastrointestinal bleeding or signs of infection, to rule out SBP. An ascitic neutrophil count >250/mm³ confirms SBP, necessitating immediate empirical antibiotic therapy tailored to local resistance patterns. (Quality of evidence: moderate; Recommendation: strong)
3. Dietary Salt Restriction: Patients should restrict dietary sodium intake to no more than 5–6.5 grams per day (87–113 mmol), equivalent to a no-added-salt diet, to manage fluid accumulation effectively. (Quality of evidence: moderate; Recommendation: strong)
4. Diuretic Therapy: For initial moderate ascites, spironolactone monotherapy is recommended. In cases of recurrent severe ascites, combination therapy with spironolactone and furosemide is advised. Regular monitoring for adverse events such as electrolyte imbalances and renal impairment is essential. (Quality of evidence: moderate; Recommendation: strong)
5. Large Volume Paracentesis (LVP): LVP is a safe and effective treatment for refractory ascites. Informed consent is required, and routine coagulation studies or prophylactic blood product infusions before the procedure are not recommended. (Quality of evidence: moderate; Recommendation: strong)
6. Use of Human Albumin Solution (HAS): After LVP exceeding 5 liters, infusion of HAS at 8 grams per liter of ascites removed is strongly recommended to prevent circulatory dysfunction. (Quality of evidence: high; Recommendation: strong)
7. Transjugular Intrahepatic Portosystemic Shunt (TIPSS): TIPSS should be considered for patients with refractory ascites not responding to medical therapy, with caution exercised in patients over 70 years or those with significant comorbidities. (Quality of evidence: high; Recommendation: strong)
8. Non-Selective Beta-Blockers (NSBBs): The presence of refractory ascites is not a contraindication for NSBB therapy. Patients should be closely monitored, and dose adjustments made in cases of hypotension or renal dysfunction. (Quality of evidence: moderate; Recommendation: strong)
9. Palliative Care: Patients unsuitable for liver transplantation should be offered palliative care referral to focus on symptom management and quality of life improvement. Alternative interventions for refractory ascites may also be considered. (Quality of evidence: weak; Recommendation: strong)

Conclusion: Implementation of these evidence-based guidelines is expected to enhance patient care by promoting early diagnosis, preventing complications, and standardizing management strategies for ascites in cirrhosis. Adherence to these recommendations can improve clinical outcomes, reduce hospitalizations, and enhance the quality of life for affected patients.

Reference: Aithal GP, Palaniyappan N, China L, et al. Guidelines on the management of ascites in cirrhosis. Gut. 2021;70(1):9–29. DOI: http://doi.org/10.1136/gutjnl-2020-321790

 

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RCT: Liberal Transfusion Strategy Reduced Unfavorable Neurological Outcomes in Acute Brain Injury

12 Oct, 2024 | 11:01h | UTC

Background: Patients with acute brain injury frequently develop anemia, and the optimal hemoglobin threshold for red blood cell transfusion in this population remains uncertain. Previous studies have shown conflicting results regarding the benefits of liberal versus restrictive transfusion strategies on neurological outcomes.

Objective: To determine whether a liberal transfusion strategy (hemoglobin threshold <9 g/dL) reduces the occurrence of unfavorable neurological outcomes at 180 days compared to a restrictive strategy (hemoglobin threshold <7 g/dL) in patients with acute brain injury.

Methods: The TRAIN trial, a multicenter, phase 3, randomized clinical trial, was conducted across 72 ICUs in 22 countries. It included patients with traumatic brain injury, aneurysmal subarachnoid hemorrhage, or intracerebral hemorrhage, who had hemoglobin levels below 9 g/dL within the first 10 days post-injury. Participants were randomized to a liberal strategy (transfusion triggered by hemoglobin <9 g/dL) or a restrictive strategy (transfusion triggered by hemoglobin <7 g/dL), with primary outcomes measured by the occurrence of an unfavorable neurological outcome, defined by a Glasgow Outcome Scale Extended score of 1-5 at 180 days.

Results: Among 820 patients who completed the trial (mean age 51 years; 45.9% women), 806 had data on the primary outcome (393 liberal, 413 restrictive). The liberal group received a median of 2 units of blood (IQR, 1–3), while the restrictive group received a median of 0 units (IQR, 0–1), with an absolute mean difference of 1.0 unit (95% CI, 0.87–1.12 units). At 180 days, 62.6% of patients in the liberal group had an unfavorable neurological outcome compared to 72.6% in the restrictive group (absolute difference –10.0%; 95% CI, –16.5% to –3.6%; adjusted relative risk 0.86; P = .002). The effect was consistent across prespecified subgroups. Cerebral ischemic events were lower in the liberal group (8.8% vs 13.5%; relative risk 0.65; 95% CI, 0.44–0.97). No significant differences were observed in 28-day survival or other secondary outcomes.

Conclusions: In patients with acute brain injury and anemia, a liberal transfusion strategy resulted in a lower rate of unfavorable neurological outcomes at 180 days compared to a restrictive strategy.

Implications for Practice: A liberal transfusion threshold of 9 g/dL may improve neurological outcomes in patients with acute brain injury by reducing cerebral ischemic events. Clinicians should consider adopting a higher hemoglobin threshold for transfusion in this population, weighing the benefits against potential risks associated with transfusions, such as infection or lung injury.

Study Strengths and Limitations: Strengths include the large, multicenter international design and blinding of outcome assessors. Limitations involve the open-label nature, potential detection bias in assessing cerebral ischemic events, lack of standardized neuroprognostication, and incomplete assessment of concomitant interventions.

Future Research: Further studies are needed to confirm these findings in specific subgroups of acute brain injury, to explore optimal transfusion strategies, and to assess long-term outcomes and potential risks associated with liberal transfusion thresholds.

Reference: Taccone FS, et al. (2024) Restrictive vs Liberal Transfusion Strategy in Patients With Acute Brain Injury: The TRAIN Randomized Clinical Trial. JAMA. DOI: http://doi.org/10.1001/jama.2024.20424

 

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RCT: Tele-ICU Intervention Did Not Significantly Reduce ICU Length of Stay in Critically Ill Patients

10 Oct, 2024 | 17:40h | UTC

Background: Telemedicine in critical care, particularly through tele-ICU interventions, has gained traction as a potential solution to the global shortage of intensivists. These systems, which include remote intensivist-led care, have shown promise in improving outcomes, but robust evidence from randomized clinical trials is lacking. The TELESCOPE trial was conducted to assess whether daily remote multidisciplinary rounds combined with monthly audit and feedback meetings could reduce ICU length of stay (LOS) compared with standard care.

Objective: The primary objective of the TELESCOPE trial was to determine if a tele-ICU intervention, involving remote daily multidisciplinary rounds and monthly performance audits led by a board-certified intensivist, could reduce ICU LOS compared to usual care.

Methods: This was a cluster randomized clinical trial involving 30 general ICUs in Brazil, enrolling all consecutive adult patients admitted between June 2019 and April 2021. A total of 17,024 patients were included, with 15 ICUs receiving the tele-ICU intervention and 15 receiving standard care. The intervention consisted of daily remote rounds led by an intensivist, monthly audit meetings, and the provision of evidence-based protocols. The primary outcome was ICU LOS, and secondary outcomes included hospital mortality, ICU efficiency, and various infection rates.

Results: There was no statistically significant difference in ICU LOS between the intervention and control groups (mean LOS: 8.1 days in the tele-ICU group vs. 7.1 days in the usual care group; percentage change, 8.2%; 95% CI, −5.4% to 23.8%; P = .24). Hospital mortality was also similar (41.6% vs. 40.2%; odds ratio, 0.93; 95% CI, 0.78-1.12). No significant differences were found in secondary outcomes, including rates of central line-associated bloodstream infections, ventilator-associated events, or ventilator-free days at 28 days.

Conclusions: The tele-ICU intervention did not reduce ICU LOS in critically ill patients. The lack of observed benefit may be due to suboptimal implementation, variable adherence by local teams, and the high severity of illness in the patient population.

Implications for Practice: While tele-ICU models hold potential, this study suggests that remote intensivist-led care, as implemented in the TELESCOPE trial, may not be sufficient to improve outcomes in high-resource ICU settings with critically ill patients.

Study Strengths and Limitations: The study’s strengths include its pragmatic design, the large number of patients enrolled, and its reflection of real-world ICU settings. However, limitations include the unblinded nature of the trial, suboptimal adherence to the tele-ICU protocol in some centers, and the strain on ICU resources during the COVID-19 pandemic, which may have affected the trial’s outcomes.

Future Research: Further studies should explore how tele-ICU interventions can be optimized, with a focus on identifying the ICU environments and patient populations most likely to benefit. Trials should also address potential barriers to effective implementation, such as staff engagement and local resource constraints.

Reference: Pereira AJ, et al. (2024) Effect of Tele-ICU on Clinical Outcomes of Critically Ill Patients: The TELESCOPE Randomized Clinical Trial. JAMA. DOI: http://doi.org/10.1001/jama.2024.20651

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Meta-Analysis: Oral Anticoagulant Monotherapy Reduced Bleeding Without Increasing Ischemic Events in AF and Stable CAD

9 Oct, 2024 | 11:13h | UTC

Background: Atrial fibrillation (AF) patients with stable coronary artery disease (CAD) often require both oral anticoagulants (OACs) for stroke prevention and antiplatelet therapy for CAD management. However, dual antithrombotic therapy (DAT) increases bleeding risk. The optimal antithrombotic regimen in this population remains unclear.

Objective: To evaluate whether OAC monotherapy reduces major bleeding without increasing ischemic events compared to DAT in patients with AF and stable CAD.

Methods: This meta-analysis followed PRISMA guidelines, pooling data from three randomized controlled trials (RCTs) involving 3,945 patients with AF and stable CAD. The trials included used various OACs (rivaroxaban, edoxaban, or warfarin/DOAC) and compared them with DAT. The primary outcomes were all-cause death, cardiovascular death, and major bleeding. Secondary outcomes included stroke (ischemic and hemorrhagic) and myocardial infarction (MI).

Results: OAC monotherapy significantly reduced the risk of major bleeding compared to DAT (3.4% vs 5.8%; RR: 0.55; 95% CI: 0.32–0.95; p=0.03). There were no significant differences between groups in all-cause death (4.2% vs 5.4%; RR: 0.85; 95% CI: 0.49–1.48; p=0.57), cardiovascular death (2.4% vs 3.0%; RR: 0.84; 95% CI: 0.50–1.41; p=0.50), any stroke event (2.2% vs 3.1%; RR: 0.74; 95% CI: 0.46–1.18; p=0.21), or myocardial infarction (RR: 1.57; 95% CI: 0.79–3.12; p=0.20).

Conclusions: In patients with AF and stable CAD, OAC monotherapy significantly reduces major bleeding risk compared to DAT without increasing the risk of ischemic events or mortality.

Implications for Practice: OAC monotherapy may be a preferable antithrombotic strategy in patients with AF and stable CAD, balancing effective thromboembolic protection with a lower bleeding risk. Clinicians should consider OAC monotherapy to simplify antithrombotic regimens and reduce bleeding complications, especially beyond one year after coronary events or interventions.

Study Strengths and Limitations: Strengths include the inclusion of recent large-scale RCTs and the focus on a clinically relevant patient population. Limitations involve reliance on study-level data, limited number of trials, and potential heterogeneity among included studies. The duration of DAT was not consistently available, and individual patient data meta-analysis may provide more detailed insights.

Future Research: Additional large-scale RCTs and individual patient data meta-analyses are needed to confirm these findings and to determine the optimal duration and type of antithrombotic therapy in patients with AF and stable CAD.

Reference: Ahmed M., et al. (2024). Meta-Analysis Comparing Oral Anticoagulant Monotherapy Versus Dual Antithrombotic Therapy in Patients With Atrial Fibrillation and Stable Coronary Artery Disease. Clin Cardiol, 47(10), e70026. DOI: http://doi.org/10.1002/clc.70026

 

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Umbrella Review: 5-Day Antibiotic Courses Effective for Non-ICU Community-Acquired Pneumonia or Exacerbations of COPD

6 Oct, 2024 | 17:12h | UTC

Background: Respiratory tract infections (RTIs) significantly contribute to global disease burden and antibiotic usage. Optimizing antibiotic treatment duration is crucial for antimicrobial stewardship to minimize resistance. Despite evidence supporting shorter antibiotic courses for RTIs, prolonged treatment durations persist in clinical practice.

Objective: To evaluate the current evidence base for optimal antibiotic treatment durations in RTIs and determine whether shorter courses are supported.

Methods: An umbrella review was conducted by searching Ovid MEDLINE, Embase, and Web of Science up to May 1, 2024, without language restrictions. Systematic reviews comparing antibiotic treatment durations for community-acquired pneumonia (CAP), acute exacerbations of chronic obstructive pulmonary disease (AECOPD), hospital-acquired pneumonia (HAP), acute sinusitis, and streptococcal pharyngitis, tonsillitis, or pharyngotonsillitis in adults were included. Pediatric-focused reviews were excluded. Quality assessments utilized the AMSTAR 2 tool for reviews and the Cochrane risk-of-bias tool (version 1) for randomized controlled trials (RCTs). The GRADE approach determined the overall quality of evidence.

Results: Thirty systematic reviews were included, generally of low to critically low quality. For non-ICU CAP (14 reviews), moderate-quality evidence supports a 5-day antibiotic course, with insufficient data for shorter durations. In AECOPD (eight reviews), a 5-day treatment was non-inferior to longer courses regarding clinical and microbiological cure, with similar or fewer adverse events. Evidence for non-ventilator-associated HAP is lacking. In acute sinusitis, shorter regimens appear effective, but further research is needed for patients requiring antibiotics. For pharyngotonsillitis (eight reviews), evidence supports short-course cephalosporin therapy but not short-course penicillin when dosed three times daily.

Conclusions: Evidence supports a 5-day antibiotic treatment duration for non-ICU CAP and AECOPD in clinically improving patients. Implementing this evidence in practice is essential. High-quality RCTs are needed to assess shorter durations for CAP and AECOPD, establish optimal durations for HAP and acute sinusitis, and evaluate short-course penicillin with optimal dosing in pharyngotonsillitis.

Implications for Practice: Clinicians should adopt 5-day antibiotic courses for non-ICU CAP and AECOPD in patients showing clinical improvement, aligning with antimicrobial stewardship objectives to reduce unnecessary antibiotic exposure and resistance development.

Study Strengths and Limitations: Strengths include a comprehensive search and assessment of systematic reviews and meta-analyses. Limitations involve the generally low quality of included reviews and RCTs, with many studies exhibiting unclear or high risk of bias. Heterogeneity in definitions of short-course treatment and variability in patient populations and settings were also noted.

Future Research: High-quality RCTs are required to investigate antibiotic durations shorter than 5 days for CAP and AECOPD, determine optimal treatment lengths for HAP and acute sinusitis, and assess short-course penicillin therapy with optimal dosing schedules in pharyngotonsillitis.

Reference: Kuijpers SME, et al. (2024) The evidence base for the optimal antibiotic treatment duration of upper and lower respiratory tract infections: an umbrella review. Lancet Infect Dis. DOI: http://doi.org/10.1016/S1473-3099(24)00456-0

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Aspirin vs. Clopidogrel Monotherapy After PCI: 1-Year Follow-Up of the STOPDAPT-3 Trial

6 Oct, 2024 | 16:51h | UTC

Background: Following percutaneous coronary intervention (PCI) with drug-eluting stents (DES), patients are typically managed with dual antiplatelet therapy (DAPT). Recent evidence suggests that monotherapy with a P2Y12 inhibitor may reduce bleeding risks compared to aspirin monotherapy, but no prior trials have directly compared these regimens beyond one month of DAPT. The STOPDAPT-3 trial aimed to evaluate the cardiovascular and bleeding outcomes of aspirin versus clopidogrel monotherapy following a short duration of DAPT.

Objective: To compare the efficacy and safety of aspirin monotherapy with clopidogrel monotherapy from 1 month to 1 year after PCI with DES, focusing on cardiovascular and bleeding outcomes.

Methods: The STOPDAPT-3 trial was a prospective, multicenter, open-label, randomized clinical trial conducted in Japan. A total of 6002 patients with acute coronary syndrome (ACS) or high bleeding risk (HBR) were randomized to either a 1-month DAPT regimen followed by aspirin monotherapy (aspirin group, n=2920) or 1-month prasugrel monotherapy followed by clopidogrel monotherapy (clopidogrel group, n=2913). The primary endpoints were a composite of cardiovascular events (cardiovascular death, myocardial infarction, stent thrombosis, or ischemic stroke) and major bleeding (Bleeding Academic Research Consortium 3 or 5).

Results: At the 1-year follow-up, both the aspirin and clopidogrel groups had comparable cardiovascular outcomes (4.5% incidence in both groups; HR 1.00, 95% CI 0.77–1.30, P=0.97). Bleeding rates were also similar between groups (aspirin: 2.0%; clopidogrel: 1.9%; HR 1.02, 95% CI 0.69–1.52, P=0.92). No significant differences were observed in secondary outcomes, including all-cause mortality, myocardial infarction, stent thrombosis, or revascularization. Additionally, adherence to the assigned monotherapy at 1 year was high in both groups (87.5% for aspirin; 87.2% for clopidogrel).

Conclusions: Aspirin monotherapy, compared to clopidogrel monotherapy, resulted in similar cardiovascular and bleeding outcomes during the 1-year follow-up after PCI with DES. Both therapies appear equally effective and safe for use following short-duration DAPT.

Implications for Practice: These findings suggest that either aspirin or clopidogrel monotherapy could be safely used following a short course of DAPT, with similar clinical outcomes. In regions where more potent P2Y12 inhibitors are not widely used, aspirin monotherapy remains a cost-effective and safe alternative.

Study Strengths and Limitations: The study’s strengths include a large sample size and a well-structured, multicenter design. Limitations include the lack of randomization after 1 month and the high prescription of proton pump inhibitors, which may have affected bleeding outcomes. Additionally, the follow-up period of 1 year may be too short to detect long-term differences.

Future Research: Longer-term studies are needed to confirm the findings, particularly regarding cardiovascular outcomes beyond 1 year. Further research is also required to evaluate the impact of aspirin versus more potent P2Y12 inhibitors in diverse populations and clinical settings.

Reference: Watanabe H., et al. (2024). Aspirin vs. clopidogrel monotherapy after percutaneous coronary intervention: 1-year follow-up of the STOPDAPT-3 trial. European Heart Journal. DOI: https://doi.org/10.1093/eurheartj/ehae617

 

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RCT: Early Surgical AVR Improved Outcomes in Asymptomatic Severe Aortic Stenosis

6 Oct, 2024 | 16:29h | UTC

Background: Severe aortic stenosis (AS) is a prevalent valvular heart disease requiring intervention in symptomatic patients. The optimal timing for surgical aortic valve replacement (AVR) in truly asymptomatic patients with severe AS and normal left ventricular (LV) systolic function remains uncertain and is under investigation.

Objective: To determine whether early surgical AVR improves clinical outcomes compared to conservative management with watchful waiting in asymptomatic patients with severe AS and normal LV ejection fraction (LVEF ≥50%).

Methods: The AVATAR trial was a multicenter, randomized controlled trial involving 157 low-risk, asymptomatic patients (mean age 67 years, 57% men) with severe AS and normal LVEF. Patients were randomized to early surgical AVR (n=78) or conservative treatment (n=79). All participants had negative exercise stress tests to confirm asymptomatic status. The primary composite endpoint included all-cause death, acute myocardial infarction, stroke, or unplanned hospitalization for heart failure (HF). Secondary outcomes encompassed individual components of the primary endpoint, cardiovascular death, serious adverse events, and procedural metrics.

Results: Over a median follow-up of 63 months, the primary composite endpoint occurred in 23.1% of the early surgery group versus 46.8% of the conservative group (hazard ratio [HR] 0.42; 95% confidence interval [CI], 0.24–0.73; P=0.002). All-cause mortality was significantly lower in the early surgery group (16.7% vs. 34.2%; HR 0.44; 95% CI, 0.23–0.85; P=0.012). Unplanned HF hospitalizations were also reduced (4.0% vs. 17.0%; HR 0.21; 95% CI, 0.06–0.73; P=0.007). There were no significant differences in stroke rates between the groups. Serious adverse events occurred less frequently in the early surgery group (26.4% vs. 49.4%; P=0.013). Sudden cardiac death was less common in the early surgery group, though not statistically significant (5.1% vs. 11.4%; P=0.17).

Conclusions: Early surgical AVR in asymptomatic patients with severe AS and normal LVEF significantly improved clinical outcomes, including reductions in all-cause mortality and HF hospitalizations, compared to conservative management.

Implications for Practice: These findings support considering early surgical AVR in truly asymptomatic patients with severe AS and normal LV function to reduce the risk of adverse events and improve long-term outcomes. Clinicians should weigh the benefits of early intervention against surgical risks, emphasizing careful patient selection and monitoring.

Study Strengths and Limitations: Strengths of the study include its randomized design, extended follow-up period, and strict inclusion of truly asymptomatic patients confirmed by negative exercise testing. Limitations involve a smaller sample size than initially projected, potential impacts of the COVID-19 pandemic on follow-up and healthcare access, and early termination of enrollment, which may affect the generalizability of the results.

Future Research: Further large-scale randomized trials are needed to validate these findings and explore the role of early intervention strategies, including transcatheter aortic valve implantation (TAVI), in asymptomatic patients with severe AS.

Reference: Banovic M, et al. (2024). Aortic Valve Replacement vs. Conservative Treatment in Asymptomatic Severe Aortic Stenosis: Long-Term Follow-Up of the AVATAR Trial. European Heart Journal. DOI: https://doi.org/10.1093/eurheartj/ehae585

 

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Summary of the review “Neuroleptic Malignant Syndrome”

6 Oct, 2024 | 16:20h | UTC

In a comprehensive review published in the New England Journal of Medicine, Wijdicks and Ropper discuss neuroleptic malignant syndrome (NMS), a rare but potentially fatal complication of antipsychotic therapy characterized by fever, muscle rigidity, and autonomic dysfunction. Given the widespread use of dopamine-blocking agents across various medical specialties, it is crucial for practicing physicians to recognize and manage this syndrome promptly to improve patient outcomes.

Key Aspects Influencing Patient Care:

• Epidemiology and Risk Factors:
  • NMS occurs in approximately 0.02 to 3% of patients exposed to dopamine-blocking agents.
  • Risk factors include dehydration, high doses of antipsychotics, rapid dose escalation, intramuscular administration, and prior episodes of NMS.
  • Both first-generation (typical) and second-generation (atypical) antipsychotics can cause NMS, though it may be less severe with atypical agents.
• Clinical Presentation:
  • Hyperthermia: Elevated temperatures often exceeding 40°C.
  • Muscle Rigidity: Lead-pipe rigidity leading to rhabdomyolysis and elevated creatine kinase levels.
  • Autonomic Dysfunction: Tachycardia, fluctuating blood pressure, diaphoresis.
  • Altered Mental Status: Ranges from agitation to stupor or catatonia.
  • Laboratory Findings: Leukocytosis, electrolyte imbalances, and signs of renal impairment.
• Diagnosis:
  • Based on clinical criteria including recent exposure to dopamine antagonists and presence of key symptoms.
  • Important to differentiate from serotonin syndrome, malignant hyperthermia, heat stroke, and severe catatonia.
• Management:
  • Immediate Discontinuation of the offending agent.
  • Supportive Care in ICU:
    • Stabilize vital signs and manage autonomic instability.
    • Aggressive hydration to prevent renal failure from rhabdomyolysis.
    • Cooling measures for hyperthermia.
  • Pharmacologic Interventions:
    • Dantrolene: Reduces muscle rigidity and hyperthermia.
    • Dopamine Agonists: Bromocriptine or amantadine may reverse dopamine blockade.
    • Benzodiazepines: Lorazepam for sedation and muscle relaxation.
  • Monitoring for Complications:
    • Watch for respiratory failure, renal dysfunction, electrolyte disturbances, and cardiac arrhythmias.
  • Electroconvulsive Therapy (ECT):
    • Considered in refractory cases unresponsive to medical management.
• Outcome and Prognosis:
  • Recovery typically occurs within 7 to 11 days with appropriate treatment.
  • Mortality rates have decreased but can reach up to 15% within one year due to complications.
  • Rechallenge with Antipsychotics:
    • If necessary, reintroduce antipsychotics cautiously after full recovery, using low doses and slow titration.
    • Prefer atypical agents and monitor closely for recurrence.

Clinical Implications:

• Early Recognition: Timely identification of NMS is critical for initiating life-saving interventions.
• Interdisciplinary Approach: Collaboration among psychiatrists, intensivists, neurologists, and other specialists enhances patient care.
• Education and Prevention:
  • Educate healthcare providers about the signs and risk factors of NMS.
  • Monitor patients on antipsychotics closely, especially during dose changes or when using high-potency agents.

Reference: Wijdicks, E. F. M., & Ropper, A. H. (2024). Neuroleptic Malignant Syndrome. New England Journal of Medicine, 391(12), 1130–1138. DOI: 10.1056/NEJMra2404606

 

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Guideline Summary: Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitors for Adults with Chronic Kidney Disease

4 Oct, 2024 | 11:14h | UTC

Introduction

A recent clinical practice guideline published in The BMJ titled “Sodium-glucose cotransporter-2 (SGLT-2) inhibitors for adults with chronic kidney disease” provides evidence-based recommendations on the use of SGLT-2 inhibitors in adults with chronic kidney disease (CKD), regardless of diabetes status. The guideline aims to assist clinicians in making informed decisions to improve patient outcomes in CKD management.

Key Recommendations and Patient Care Implications

1. Risk Stratification
   • Assessment: Patients with CKD should be stratified based on their risk of disease progression and complications using estimated glomerular filtration rate (eGFR) and albuminuria levels, following the Kidney Disease Improving Global Outcomes (KDIGO) classification.
   • Clinical Implication: Proper risk stratification guides the intensity of treatment and monitoring.
2. Use of SGLT-2 Inhibitors
   • Low to Moderate Risk Patients: For adults at low or moderate risk, the guideline suggests administering SGLT-2 inhibitors (weak recommendation in favor).
     • Patient Care Impact: Clinicians should discuss potential benefits and risks with patients, considering individual preferences.
   • High to Very High Risk Patients: For adults at high or very high risk, a strong recommendation is made to administer SGLT-2 inhibitors.
     • Patient Care Impact: Clinicians should prioritize initiating SGLT-2 inhibitors in these patients to reduce risks of mortality and progression to kidney failure.
3. Benefits of SGLT-2 Inhibitors
   • Outcomes: Reduction in all-cause mortality, cardiovascular mortality, hospitalization for heart failure, kidney failure, non-fatal myocardial infarction, and non-fatal stroke.
   • Clinical Implication: SGLT-2 inhibitors provide significant protective effects on cardiovascular and kidney health in CKD patients.
4. Potential Harms and Monitoring
   • Adverse Effects: Minimal increase in risks of acute kidney injury requiring dialysis, bone fractures, lower limb amputations, ketoacidosis, genital infections, or symptomatic hypovolemia.
   • Patient Counseling: Patients should be informed about possible side effects and advised on when to seek medical attention.
   • Monitoring: Routine laboratory monitoring is not generally necessary, except in high-risk individuals.
5. Practical Considerations for Prescribing
   • Initiation: Start SGLT-2 inhibitors in patients with eGFR ≥20 mL/min/1.73 m².
   • Continuation: Medications can be continued even if eGFR falls below 20 mL/min/1.73 m² until dialysis is initiated.
   • Dosage: Initiate at the highest possible dose without the need for titration.
   • Drug Selection: Canagliflozin, dapagliflozin, and empagliflozin are suitable options.
   • Concurrent Medications: Review and adjust diuretics to prevent volume depletion.
6. Patient Education and Self-Management
   • Sick Day Rules: Advise patients to temporarily discontinue SGLT-2 inhibitors during acute illnesses causing dehydration.
   • Lifestyle Modifications: Encourage adherence to medication and healthy lifestyle changes to enhance treatment efficacy.
7. Applicability and Exceptions
   • Applicable Populations: Recommendations apply broadly to adults with CKD, with or without type 2 diabetes.
   • Exceptions: Caution or alternative approaches may be necessary for patients:
     • Receiving kidney replacement therapy.
     • With kidney transplants, polycystic kidney disease, rare kidney diseases.
     • With eGFR <20 mL/min/1.73 m² not on replacement therapy.

Conclusion

The guideline underscores the importance of incorporating SGLT-2 inhibitors into the management plan for adults with CKD to improve survival and reduce cardiovascular and kidney-related complications. Clinicians should evaluate each patient’s risk profile and engage in shared decision-making to optimize treatment outcomes.

Reference: Agarwal A, Zeng X, Li S, et al. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors for adults with chronic kidney disease: a clinical practice guideline. BMJ. DOI: https://doi.org/10.1136/bmj-2024-080257

 

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RCT: H. pylori Screening Added to Fecal Immunochemical Testing Did Not Reduce Gastric Cancer Incidence or Mortality

4 Oct, 2024 | 11:00h | UTC

Background: Gastric cancer is a leading cause of cancer-related mortality worldwide, particularly in East Asia. Helicobacter pylori infection is a well-established risk factor for gastric cancer development. While eradication therapy may prevent gastric cancer, the effectiveness of community-based H. pylori screening on gastric cancer incidence and mortality remains uncertain.

Objective: To determine whether adding H. pylori stool antigen (HPSA) testing to fecal immunochemical test (FIT) screening reduces gastric cancer incidence and mortality compared to FIT screening alone.

Methods: In a pragmatic randomized clinical trial conducted in Changhua County, Taiwan (2014–2018), 152,503 residents aged 50 to 69 years eligible for biennial FIT screening were randomized to receive an invitation for HPSA testing plus FIT (n = 63,508) or FIT alone (n = 88,995). Participants in the HPSA + FIT group with positive HPSA results were offered antibiotic eradication therapy. Primary outcomes were gastric cancer incidence and mortality, assessed via national cancer and death registries.

Results: Participation rates were higher in the HPSA + FIT group (49.6%) than in the FIT-alone group (35.7%). In the HPSA + FIT group, 38.5% tested positive for HPSA, and 71.4% of these received antibiotic treatment, achieving a 91.9% eradication rate. Over a median follow-up of approximately 5 years, gastric cancer incidence did not differ significantly between the HPSA + FIT and FIT-alone groups (0.032% vs 0.037%; mean difference –0.005%; 95% CI, –0.013% to 0.003%; P = .23). Gastric cancer mortality rates were also similar (0.015% vs 0.013%; mean difference 0.002%; 95% CI, –0.004% to 0.007%; P = .57). Adjusted analyses accounting for participation rates, follow-up duration, and baseline characteristics showed a lower gastric cancer incidence in the HPSA + FIT group (RR 0.79; 95% CI, 0.63–0.98; P = .04), but no difference in mortality (RR 1.02; 95% CI, 0.73–1.40; P = .91). Adverse effects from antibiotics were mild, with abdominal pain or diarrhea occurring in 2.1%.

Conclusions: An invitation to HPSA testing combined with FIT did not significantly reduce gastric cancer incidence or mortality compared to FIT alone over a median follow-up of about 5 years. Adjusted analyses suggest a potential reduction in gastric cancer incidence but not mortality when accounting for participation rates and follow-up duration.

Implications for Practice: Adding H. pylori screening to existing FIT programs may not significantly reduce gastric cancer incidence or mortality in the short term, possibly due to low participation rates, incomplete eradication, and limited follow-up. Clinicians should consider these factors when implementing community-based H. pylori screening and weigh the benefits against resource utilization and patient adherence.

Study Strengths and Limitations: Strengths include a large sample size and integration of HPSA testing into an existing FIT screening infrastructure. Limitations encompass differences in participation rates and baseline characteristics between groups, a relatively short follow-up period, and only 71.4% of HPSA-positive participants receiving eradication therapy, which may have reduced the ability to detect significant effects.

Future Research: Longer-term studies with higher participation and eradication rates are needed to assess the long-term benefits of H. pylori screening on gastric cancer incidence and mortality. Research should explore strategies to improve screening uptake and treatment adherence.

Reference: Lee Y-C, et al. (2024) Screening for Helicobacter pylori to Prevent Gastric Cancer: A Pragmatic Randomized Clinical Trial. JAMA. DOI: http://doi.org/10.1001/jama.2024.14887

 

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Summary of “Dialysis for Chronic Kidney Failure: A Review”

3 Oct, 2024 | 22:46h | UTC

In their comprehensive review published in JAMA on October 2, 2024, Dr. Jennifer E. Flythe and Dr. Suzanne Watnick discuss current evidence regarding the pathophysiology, diagnosis, and management of dialysis-dependent chronic kidney failure. The article emphasizes clinical considerations that directly impact patient care, particularly in the initiation and management of dialysis therapy.

Key Aspects Influencing Patient Care

1. Initiation of Dialysis
   • No Specific eGFR Threshold: There is no recommended estimated glomerular filtration rate (eGFR) for starting dialysis. Decisions should be individualized, focusing on persistent uremic symptoms (e.g., nausea, fatigue), volume overload (e.g., dyspnea, peripheral edema), worsening eGFR, metabolic acidosis, and hyperkalemia.
   • Shared Decision-Making: The timing of dialysis initiation should involve a collaborative approach between clinicians and patients, considering symptoms, laboratory trends, and patient preferences.
   • No Mortality Benefit from Early Initiation: A randomized clinical trial found no mortality advantage in starting dialysis at higher eGFR levels (10–14 mL/min/1.73 m²) compared to lower levels (5–7 mL/min/1.73 m²).
2. Dialysis Modalities
   • Hemodialysis vs. Peritoneal Dialysis: Observational data indicate no significant difference in 5-year mortality rates between the two modalities.
   • Modality Selection Factors: Decisions should consider patient lifestyle, comorbid conditions, availability of home support, and resource accessibility.
3. Common Complications
   • Cardiovascular Risks: Cardiovascular complications, such as arrhythmias and cardiac arrest, are leading causes of death among dialysis patients.
   • Infections:
     • Hemodialysis: Catheter-related bloodstream infections occur at rates of 1.1 to 5.5 episodes per 1000 catheter-days.
     • Peritoneal Dialysis: Peritonitis occurs at a rate of 0.26 episodes per patient-year.
   • Systemic Complications: Anemia, hyperphosphatemia, hypocalcemia, and hypertension are prevalent and often require pharmacologic intervention.
   • Dialysis-Related Issues: Hypotension during dialysis, muscle cramps, itching, and vascular access malfunction can hinder effective treatment.
4. Management Strategies
   • Anemia: Initiate intravenous iron and/or erythropoietin-stimulating agents when hemoglobin is below 10 g/dL, aiming to maintain levels between 10 and 11.5 g/dL.
   • Mineral and Bone Disorders: Use dietary phosphorus restrictions and phosphorus binders; monitor and manage parathyroid hormone levels to mitigate fracture risk.
   • Hypertension: Implement dietary salt restriction, adjust ultrafiltration, and prescribe antihypertensive medications, recognizing there’s no specific BP target in dialysis patients.
5. Practical Considerations for Clinicians
   • Medication Management: Avoid nephrotoxic agents like NSAIDs and iodinated contrast media in patients with residual kidney function. Adjust dosages for medications excreted renally.
   • Symptom Control: Address common symptoms such as pruritus with appropriate therapies such as oral antihistamines and moisturizers. Difelikefalin is a new agent that can also be used.
   • Patient Education: Counsel on dietary restrictions (salt, fluid, potassium) and ensure vaccinations are up to date, including hepatitis B, pneumococcal, COVID-19, and RSV vaccines.

Conclusion

For the over 540,000 patients in the U.S. receiving maintenance dialysis, individualized care plans that involve shared decision-making are crucial. Understanding when to initiate dialysis, selecting the appropriate modality, managing complications, and addressing patient-specific needs can significantly influence outcomes and quality of life.

Reference: Flythe JE, Watnick S. Dialysis for Chronic Kidney Failure: A Review. JAMA. Published online October 2, 2024. doi:10.1001/jama.2024.16338

 

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RCT: Telehealth-Delivered Early Palliative Care Equivalent to In-Person Care in Advanced Lung Cancer

26 Sep, 2024 | 15:06h | UTC

Background: Patients with advanced lung cancer often face a high symptom burden and decreased quality of life (QOL), but access to early palliative care, which can improve these outcomes, remains limited. While telehealth has become increasingly utilized due to the COVID-19 pandemic, it is unclear whether virtual palliative care is as effective as in-person care.

Objective: To compare the effect of early palliative care delivered via secure video vs in-person visits on the quality of life of patients with advanced non–small cell lung cancer (NSCLC).

Methods: This multisite, randomized comparative effectiveness trial enrolled 1250 adults with advanced NSCLC from 22 cancer centers in the US between June 2018 and May 2023. Participants were randomized to receive either early palliative care via video visits or in person every four weeks. The primary outcome was QOL measured by the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire at 24 weeks. Secondary outcomes included caregiver participation in palliative care visits and patient and caregiver satisfaction with care, mood symptoms, coping, and prognostic understanding.

Results: By week 24, patients in both groups reported equivalent QOL scores, with the video visit group scoring a mean of 99.7 compared to 97.7 in the in-person group (difference of 2.0 points, 90% CI, 0.1-3.9; P = .04 for equivalence). Both groups experienced similar improvements in QOL from baseline (mean increase of 8.4 points for video visits and 6.9 points for in-person care). Caregiver participation in palliative care visits was lower in the video visit group (36.6% vs 49.7%; P < .001). No significant differences were found between the groups in caregiver QOL, patient or caregiver satisfaction with care, mood symptoms, or coping strategies.

Conclusions: Early palliative care delivered via telehealth was equivalent to in-person visits in improving QOL for patients with advanced NSCLC. This underscores the potential of telehealth to increase access to essential palliative care services for this population without compromising care quality.

Implications for Practice: Telehealth can provide a feasible alternative to in-person palliative care, especially for patients with advanced lung cancer who face barriers to in-person visits, such as transportation challenges. However, strategies to enhance caregiver involvement in virtual visits may need to be developed.

Study Strengths and Limitations: Strengths include the large, multisite randomized design and the use of validated outcome measures. Limitations involve the COVID-19 pandemic’s impact, which caused some intervention contamination due to unavoidable video visits in the in-person group. Additionally, caregiver participation was lower than expected, potentially limiting the generalizability of results regarding caregiver outcomes.

Future Research: Further studies should explore the long-term impact of telehealth on palliative care outcomes and investigate ways to enhance caregiver involvement in virtual care.

Reference: Greer, J. A., et al. (2024). Telehealth vs In-Person Early Palliative Care for Patients With Advanced Lung Cancer: A Multisite Randomized Clinical Trial. JAMA. DOI: http://doi.org/10.1001/jama.2024.13964

 

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RCT: MRI-Guided Biopsy Reduces Overdiagnosis of Clinically Insignificant Prostate Cancer

26 Sep, 2024 | 12:22h | UTC

Background: Overdiagnosis of clinically insignificant prostate cancer is a significant issue in population-based screening programs, primarily when prostate-specific antigen (PSA) testing is followed by systematic biopsy. Magnetic resonance imaging (MRI)-guided biopsies, which avoid systematic biopsies in men with negative MRI results, have shown potential in reducing unnecessary cancer diagnoses. However, long-term data are needed to confirm the safety and efficacy of this approach.

Objective: To evaluate whether MRI-targeted biopsies, when combined with PSA screening, can reduce the detection of clinically insignificant prostate cancer without compromising the identification of clinically significant or advanced disease.

Methods: This population-based, randomized trial in Sweden (GÖTEBORG-2) enrolled 13,153 men aged 50-60 years who underwent PSA screening. Men with PSA levels ≥3 ng/mL were randomized into two groups: (1) MRI-targeted biopsy only in cases with suspicious lesions, or (2) systematic biopsy in all cases with PSA elevation. Screening occurred every 2, 4, or 8 years depending on PSA levels, with follow-up for up to four years. The primary outcome was the detection of clinically insignificant prostate cancer, and secondary outcomes included clinically significant and advanced or high-risk prostate cancer.

Results: After a median follow-up of 3.9 years, the detection of clinically insignificant prostate cancer was significantly lower in the MRI-targeted biopsy group (2.8%) compared to the systematic biopsy group (4.5%), with a relative risk (RR) of 0.43 (95% CI, 0.32-0.57; P < 0.001). The relative risk of detecting clinically significant cancer was 0.84 (95% CI, 0.66-1.07), indicating no significant difference between the two groups. Advanced or high-risk cancers were detected in 15 men in the MRI group and 23 men in the systematic group (RR, 0.65; 95% CI, 0.34-1.24). Severe adverse events occurred in five patients (three in the systematic biopsy group, two in the MRI-targeted biopsy group).

Conclusions: Omitting biopsies in men with negative MRI results substantially reduced the diagnosis of clinically insignificant prostate cancer without increasing the risk of missing clinically significant or advanced cancers. MRI-targeted biopsy strategies can effectively limit overdiagnosis while maintaining safety in screening programs.

Implications for Practice: MRI-targeted biopsies offer a promising strategy to reduce unnecessary cancer diagnoses and avoid overtreatment in prostate cancer screening. Clinicians should consider integrating MRI into prostate cancer screening algorithms, especially in cases with elevated PSA but no MRI-detected lesions. This approach may also decrease biopsy-related complications and patient anxiety.

Study Strengths and Limitations: Strengths of this trial include its population-based design, large sample size, and thorough follow-up. Limitations include its single-center setting in Sweden, which may limit generalizability to more diverse populations, and a modest participation rate of 50%.

Future Research: Further studies should assess the cost-effectiveness of widespread MRI use in prostate cancer screening and explore its utility in diverse populations. Investigations into novel biomarkers that could further refine patient selection for MRI-targeted biopsy are also warranted.

Reference: Hugosson J., et al. (2024). Results after Four Years of Screening for Prostate Cancer with PSA and MRI. N Engl J Med. DOI: https://doi.org/10.1056/NEJMoa2406050

 

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Network Meta-Analysis: Eletriptan, Rizatriptan, Sumatriptan, and Zolmitriptan Most Effective for Acute Migraine Episodes

23 Sep, 2024 | 22:34h | UTC

Background: Migraine, a highly prevalent neurological disorder, is a leading cause of disability, especially among women aged 15 to 49. Effective acute management is critical, with current guidelines recommending non-steroidal anti-inflammatory drugs (NSAIDs) and triptans for moderate to severe episodes. However, the relative efficacy of various drug interventions remains unclear, especially with newer treatments like lasmiditan and gepants entering the market.

Objective: To evaluate and compare the efficacy and tolerability of all licensed oral drugs for the acute treatment of migraine episodes in adults.

Methods: A systematic review and network meta-analysis was conducted, including 137 randomized controlled trials (RCTs) involving 89,445 participants. The study analyzed 17 drug interventions, including NSAIDs, triptans, ditans, and gepants, and compared them with placebo. Primary outcomes included pain freedom at two hours post-dose and sustained pain freedom from two to 24 hours post-dose. Certainty of evidence was assessed using the CINeMA framework, and sensitivity analyses were conducted to confirm the robustness of the findings.

Results: All active interventions outperformed placebo for pain freedom at two hours, with odds ratios ranging from 1.73 (95% CI 1.27 to 2.34) for naratriptan to 5.19 (4.25 to 6.33) for eletriptan. The most effective drugs for sustained pain freedom were eletriptan and ibuprofen. Among head-to-head comparisons, eletriptan was the most effective for pain freedom at two hours, followed by rizatriptan, sumatriptan, and zolmitriptan. Newer drugs like lasmiditan, rimegepant, and ubrogepant were less effective than the triptans and showed adverse effects like dizziness and nausea.

Conclusions: Triptans—specifically eletriptan, rizatriptan, sumatriptan, and zolmitriptan—demonstrated superior efficacy and tolerability profiles compared to newer treatments like lasmiditan and gepants. Given their efficacy, these triptans should be prioritized in acute migraine management. However, triptans are underused, and barriers to access should be addressed to ensure broader utilization. Lasmiditan and gepants may still serve as alternatives for patients contraindicated for triptans due to cardiovascular risks.

Implications for Practice: Clinicians should prioritize triptans, particularly eletriptan, rizatriptan, sumatriptan, and zolmitriptan, in managing acute migraine episodes due to their superior efficacy. Careful consideration is needed when selecting newer drugs like lasmiditan and gepants, as they may be less effective and have higher costs and adverse event risks. Cost-effectiveness and patient cardiovascular profiles should guide decision-making.

Study Strengths and Limitations: Strengths include the comprehensive inclusion of both published and unpublished data, as well as the large sample size and robust methodological framework. Limitations include moderate heterogeneity and low confidence in some comparisons due to reporting biases and imprecise treatment effects in older studies.

Future Research: Future studies should focus on re-evaluating the cardiovascular contraindications of triptans to ensure broader access. Additional research is also needed to assess the cost-effectiveness of newer treatments like lasmiditan and gepants, particularly in patients for whom triptans are unsuitable.

Reference: Karlsson WK, et al. Comparative effects of drug interventions for the acute management of migraine episodes in adults: systematic review and network meta-analysis. BMJ. 2024; DOI: https://doi.org/10.1136/bmj-2024-080107

 

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Phase 2 RCT: Ponsegromab Shows Promise for the Treatment of Cancer Cachexia

23 Sep, 2024 | 21:48h | UTC

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Summary of the review “Lipoprotein(a) and Cardiovascular Disease”

23 Sep, 2024 | 21:22h | UTC

Summary of the review “Lipoprotein(a) and Cardiovascular Disease“

By Prof Børge G Nordestgaard and Anne Langsted

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Key Takeaways for Practicing Physicians:

1. Significance of Lipoprotein(a) [Lp(a)]:
   • Causal Risk Factor: Elevated Lp(a) is a genetically determined causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis.
   • Prevalence: Approximately 1 in 5 individuals globally have high Lp(a) levels, increasing their cardiovascular risk.
2. Genetic Determinants and Ethnic Variations:
   • Genetic Influence: Over 90% genetically determined with minimal lifestyle impact.
   • Ethnic Differences:
     • Lowest levels: East Asians, Europeans, Southeast Asians.
     • Intermediate levels: South Asians, Middle Easterners, Latin Americans.
     • Highest levels: Individuals of African descent.
   • Sex Differences: Postmenopausal women have about 17% higher Lp(a) levels than men.
3. Clinical Measurement and Interpretation:
   • When to Measure:
     • Once in a Lifetime: Recommended for all individuals to measure Lp(a) at least once.
     • High-Risk Patients: Especially important in those with premature ASCVD, familial hypercholesterolaemia (FH), family history of elevated Lp(a) or early ASCVD.
   • Stability of Levels: Lp(a) levels are stable after age two and are unaffected by most lifestyle factors.
   • Interpreting Levels:
     • Elevated Risk Thresholds:
       • >30 mg/dL (≥62 nmol/L): Increased risk begins.
       • >50 mg/dL (≥105 nmol/L): Clinically significant high risk.
       • >90 mg/dL (≥190 nmol/L): Severe risk, comparable to FH.
   • Laboratory Considerations:
     • Assay Selection: Use isoform-independent assays with standardized calibration.
     • Reporting Units: Preferably in nmol/L; however, mg/dL is acceptable with appropriate conversion.
4. Impact on Patient Care:
   • Risk Stratification:
     • Independent Risk Factor: High Lp(a) increases ASCVD risk independent of other lipids.
     • Reclassification: Can reclassify patients into higher risk categories, influencing management decisions.
   • Management Strategies:
     • Current Limitations: No approved therapies specifically targeting Lp(a) reduction.
     • Aggressive Risk Factor Control:
       • LDL Cholesterol: Intensive lowering with high-intensity statins, ezetimibe, and PCSK9 inhibitors.
         • PCSK9 Inhibitors: Lower Lp(a) by ~25% and reduce cardiovascular events.
       • Lifestyle Modifications: Emphasize smoking cessation, healthy diet, physical activity, and weight management.
       • Blood Pressure and Diabetes Management: Optimize control per guidelines.
     • Avoid Unproven Therapies: Niacin is not recommended due to side effects and lack of cardiovascular benefit.
5. Familial Hypercholesterolaemia (FH):
   • Dual Risk: Elevated Lp(a) often coexists with FH, compounding cardiovascular risk.
   • Screening: Measure Lp(a) in all patients with FH and consider cascade screening in families.
6. Emerging Therapies:
   • Gene-Silencing Drugs:
     • Pelacarsen, Olpasiran, Lepodisiran: Lower Lp(a) levels by 80–98%.
     • Administration: Subcutaneous injections, varying from monthly to quarterly.
   • Small Molecule Inhibitors:
     • Muvalaplin: Oral agent reducing Lp(a) by ~65%.
   • Clinical Trials:
     • Phase 3 Trials Ongoing: Evaluating cardiovascular outcomes with significant Lp(a) reduction.
     • Potential Change in Practice: These therapies may soon provide effective options for patients with high Lp(a).
7. Practical Recommendations:
   • Include Lp(a) in Lipid Panels: Encourage laboratories to add Lp(a) measurements to standard profiles.
   • Patient Communication:
     • Educate on Risks: Explain the significance of high Lp(a) and its genetic nature.
     • Lifestyle Advice: Reinforce the importance of modifiable risk factor control.
   • Family Screening: Consider evaluating first-degree relatives due to genetic inheritance patterns.
8. Monitoring and Follow-Up:
   • Re-measurement: Generally, one measurement suffices unless a significant event (e.g., menopause) occurs.
   • Acute Phase Reactant Consideration: Be cautious interpreting levels during acute illness; recheck once stabilized.

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Conclusion:

Elevated Lp(a) is a significant and prevalent cardiovascular risk factor that is largely genetic and stable throughout life. While direct treatments are on the horizon, current management focuses on aggressive modification of other cardiovascular risk factors. Measurement of Lp(a) should become a routine part of cardiovascular risk assessment, guiding more personalized and effective patient care.

Reference: Nordestgaard, B. G., & Langsted, A. (2024). Lipoprotein(a) and cardiovascular disease. The Lancet, 404(10153), 295-306. https://doi.org/10.1016/S0140-6736(24)01308-4

 

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Summary: Perioperative Management of Patients Taking Direct Oral Anticoagulants

19 Sep, 2024 | 21:12h | UTC

Direct oral anticoagulants (DOACs)—including apixaban, rivaroxaban, edoxaban, and dabigatran—are increasingly used for stroke prevention in atrial fibrillation and for treating venous thromboembolism. Effective perioperative management of DOACs is essential to minimize bleeding and thromboembolic risks during surgical and nonsurgical procedures. Below are practical recommendations focused on the perioperative management of patients taking DOACs, based on a recent JAMA review article.

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Elective Surgical or Nonsurgical Procedures

Classify Bleeding Risk of Procedures:

1. Minimal Risk:
   • Minor dental procedures (e.g., cleaning, extractions)
   • Minor dermatologic procedures (e.g., skin lesion removal)
   • Cataract surgery
2. Low to Moderate Risk:
   • Endoscopic procedures without high-risk interventions
   • Cholecystectomy
   • Inguinal hernia repair
3. High Risk:
   • Major surgery (e.g., cancer surgery, joint replacement)
   • Procedures involving neuraxial anesthesia
   • Endoscopic procedures with high-risk interventions (e.g., large polyp removal)

DOAC Management Strategies:

1. Minimal Bleeding Risk Procedures:
   • Option 1: Continue DOACs without interruption.
   • Option 2: For added safety, withhold the morning dose on the day of the procedure (especially for twice-daily DOACs like apixaban and dabigatran).
2. Low to Moderate Bleeding Risk Procedures:
   • Preoperative:
     • Discontinue DOACs 1 day before the procedure.
     • This allows approximately 2 half-lives for drug clearance.
   • Postoperative:
     • Resume DOACs 1 day after the procedure, ensuring adequate hemostasis.
3. High Bleeding Risk Procedures:
   • Preoperative:
     • Discontinue DOACs 2 days before the procedure.
     • This allows approximately 4-5 half-lives for drug clearance.
   • Postoperative:
     • Resume DOACs 2-3 days after the procedure, based on bleeding risk and hemostasis.

Evidence Supporting These Strategies:

• The PAUSE study demonstrated that standardized interruption protocols without heparin bridging result in low rates of:
  • Thromboembolism: 0.2%–0.4%
  • Major Bleeding: 1%–2%

Postoperative DOAC Resumption:

• Assess surgical-site hemostasis before resuming DOACs.
• Delay resumption if there is ongoing bleeding or concerns about hemostasis.
• For high bleeding risk procedures, consider a longer delay (2–3 days).

Perioperative Heparin Bridging:

• Not recommended for patients on DOACs.
• Bridging increases bleeding risk without reducing thromboembolism.
• DOACs have rapid offset and onset, making bridging unnecessary.

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Special Considerations

Patients with Impaired Renal Function:

• For CrCl 30–50 mL/min:
  • Dabigatran: Extend preoperative discontinuation by an additional day.
• For CrCl <30 mL/min:
  • Dabigatran is contraindicated.
  • For other DOACs, consider extending discontinuation to 3–4 days before surgery.

Patients Undergoing Neuraxial Anesthesia:

• Discontinue DOACs for 3 days (apixaban, edoxaban, rivaroxaban) or 4 days (dabigatran) before the procedure.
• Minimizes risk of spinal or epidural hematoma.

Dental Procedures:

• Generally safe to continue DOACs.
• For added safety:
  • Omit or delay the dose on the day of the procedure.
  • Employ local hemostatic measures (e.g., tranexamic acid mouthwash).

Endoscopic Procedures:

• Low-risk procedures (e.g., diagnostic endoscopy without biopsy):
  • Follow standard DOAC interruption for low to moderate bleeding risk.
• High-risk procedures (e.g., polypectomy of large polyps):
  • Extend DOAC discontinuation by an additional day pre- and post-procedure.

Patients Unable to Resume Oral Medications Postoperatively:

• Use prophylactic low-molecular-weight heparin (LMWH) until oral intake is possible.
• Avoid therapeutic-dose LMWH due to bleeding risk.

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Emergent, Urgent, or Semiurgent Procedures

Risks:

• Higher bleeding risk: Up to 23%
• Thromboembolism risk: Up to 11%

Management Strategies:

1. Assess Time Since Last DOAC Dose:
   • If within 48 hours, consider that significant anticoagulant effect may persist.
2. Laboratory Testing (if available):
   • DOAC Level Testing:
     • ≥50 ng/mL: Consider using reversal agents.
     • <50 ng/mL: May proceed without reversal agents.
3. Use of Reversal Agents:
   • For Dabigatran:
     • Idarucizumab (5 g IV)
   • For Factor Xa Inhibitors (apixaban, rivaroxaban, edoxaban):
     • Andexanet alfa (dosing based on last dose timing and amount)
     • Prothrombin Complex Concentrates (PCCs): If andexanet alfa is unavailable or contraindicated.
4. Proceeding Without Testing:
   • If testing is unavailable and last DOAC dose was within 48 hours, consider reversal agents.
   • If >48 hours since last dose, may proceed without reversal.

Considerations:

• Reversal agents are expensive and may carry thrombotic risks.
• Use should be judicious, weighing risks and benefits.
• Consult hematology or thrombosis experts when possible.

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Key Takeaways

• Elective Procedures:
  • Utilize standardized protocols based on procedural bleeding risk.
  • Routine preoperative DOAC level testing is unnecessary.
  • Avoid heparin bridging.
• Emergent/Urgent Procedures:
  • Reversal agents may be appropriate when significant DOAC levels are present.
  • Decision to use reversal agents should consider bleeding risk, time since last dose, and availability of DOAC level testing.
• Patient Communication:
  • Ensure patients understand the plan for DOAC interruption and resumption.
  • Provide clear instructions regarding timing and dosing.
• Interdisciplinary Coordination:
  • Collaborate with surgical teams, anesthesiologists, and pharmacists.
  • Use electronic medical records and clinical decision support tools to enhance communication.

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Conclusion

By applying standardized perioperative management protocols, clinicians can effectively balance the risks of bleeding and thromboembolism in patients taking DOACs who require surgical or nonsurgical procedures. These strategies simplify decision-making, avoid unnecessary interventions like heparin bridging, and promote patient safety.

Reference: Douketis JD, Spyropoulos AC. Perioperative Management of Patients Taking Direct Oral Anticoagulants: A Review. JAMA. 2024;332(10):825–834. doi:10.1001/jama.2024.12708

 

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Summary: Community-Acquired Pneumonia

19 Sep, 2024 | 17:21h | UTC

Introduction

Community-acquired pneumonia (CAP) is a significant cause of morbidity and mortality, accounting for approximately 1.4 million emergency department visits, 740,000 hospitalizations, and 41,000 deaths annually in the United States. Effective management of CAP requires prompt and accurate diagnosis, appropriate antimicrobial therapy, and consideration of adjunctive treatments. This summary highlights key practice points from a review article in JAMA related to the diagnosis and treatment of CAP for medical professionals.

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Diagnosis of CAP

Clinical Presentation

• Signs and Symptoms: Suspect CAP in patients presenting with two or more of the following:
  • Fever (>38 °C) or hypothermia (≤36 °C)
  • Leukocytosis (>10,000/μL) or leukopenia (<4,000/μL)
  • New or increased cough
  • Dyspnea

Radiographic Confirmation

• Chest Imaging: Obtain a chest radiograph for all patients with suspected CAP to identify air space opacities or infiltrates.
  • Chest CT: Consider if the chest radiograph is inconclusive but clinical suspicion remains high.
• Differential Diagnosis: Rule out other causes of symptoms and radiographic findings, such as pulmonary embolism, heart failure, or malignancy.

Microbiological Testing

• Viral Testing:
  • SARS-CoV-2 and Influenza: Test all patients for COVID-19 and influenza during periods of community transmission, as results influence treatment decisions and infection control measures.
• Bacterial Testing:
  • Indications: Reserve sputum and blood cultures for patients with severe CAP or risk factors for methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa.
  • Risk Factors:
    • Previous infection or colonization with MRSA or P. aeruginosa.
    • Hospitalization with parenteral antibiotics within the past 90 days.

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Treatment of CAP

Empirical Antimicrobial Therapy

• Hospitalized Patients without Risk Factors for Resistant Bacteria:
  • First-Line Therapy: β-lactam plus macrolide combination.
    • Example: Ceftriaxone (1-2 g IV daily) plus azithromycin (500 mg IV or orally daily).
  • Alternative: Respiratory fluoroquinolone monotherapy (e.g., levofloxacin) if β-lactam/macrolide therapy is contraindicated.
• Patients with Severe CAP:
  • Similar to non-severe CAP but ensure coverage for atypical pathogens.
  • Consider Corticosteroids: Early administration (within 24 hours) of systemic corticosteroids may reduce mortality.
• Outpatients without Comorbidities:
  • First-Line Therapy: Amoxicillin (1 g orally three times daily) or doxycycline (100 mg orally twice daily).
• Outpatients with Comorbidities:
  • Combination Therapy: Amoxicillin/clavulanate (500 mg/125 mg orally three times daily) plus azithromycin (500 mg on day 1, then 250 mg daily).

Duration of Therapy

• Minimum Duration: Treat for a minimum of 3 days if the patient achieves clinical stability (normal vital signs) within 72 hours.
• Extended Duration: Extend to 5 days or more if the patient does not meet stability criteria by day 3 or has complications.
• Transition to Oral Therapy: Switch from intravenous to oral antibiotics when the patient can tolerate oral intake.

Antimicrobial Stewardship

• Avoid Unnecessary Antibiotics: Do not initiate antibiotics for confirmed viral CAP without evidence of bacterial coinfection.
• De-escalation: Narrow antibiotic coverage based on culture results and clinical improvement.
• Monitor for Adverse Effects: Be vigilant for antibiotic-associated complications, such as Clostridioides difficile infection.

Adjunctive Therapies

• Corticosteroids:
  • Severe CAP: Administer systemic corticosteroids (e.g., hydrocortisone 200 mg/day) within 24 hours of diagnosis to reduce mortality and complications.
  • Non-severe CAP: Routine use is not recommended due to lack of benefit and potential harm.

Secondary Prevention

• Vaccinations:
  • Pneumococcal Conjugate Vaccine: Recommend for eligible patients to prevent future pneumococcal infections.
  • Influenza Vaccine: Annual vaccination to reduce the risk of influenza-associated pneumonia.
  • COVID-19 and RSV Vaccines: Encourage vaccination per current guidelines.
• Lifestyle Modifications:
  • Smoking Cessation: Strongly advise quitting smoking to reduce the risk of CAP and improve respiratory health.
  • Alcohol Moderation: Counsel patients on reducing excessive alcohol intake.
• Management of Comorbidities:
  • Optimize treatment for chronic conditions such as chronic obstructive pulmonary disease (COPD), heart failure, and diabetes.

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Key Practice Points

1. Diagnostic Evaluation:
   • Use a combination of clinical signs, symptoms, and radiographic findings to diagnose CAP.
   • Test all patients for SARS-CoV-2 and influenza during times of community prevalence.
   • Reserve extensive pathogen testing for severe cases or those at risk for resistant organisms.
2. Antimicrobial Therapy:
   • Initiate empirical antibiotics promptly based on disease severity and risk factors.
   • Prefer β-lactam/macrolide combination therapy for most hospitalized patients.
   • Limit the duration of antibiotics to the shortest effective course to reduce resistance and adverse effects.
3. Use of Corticosteroids:
   • Consider early corticosteroid therapy in patients with severe CAP to improve outcomes.
   • Avoid routine corticosteroid use in non-severe CAP due to potential risks.
4. Antimicrobial Stewardship:
   • Reassess antibiotic therapy daily and de-escalate based on clinical response and microbiological data.
   • Transition to oral antibiotics when appropriate.
5. Preventive Measures:
   • Promote vaccinations and lifestyle changes to prevent recurrent CAP.
   • Address and manage underlying health conditions that may predispose to CAP.

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Conclusion

Effective management of CAP involves prompt diagnosis using clinical and radiographic criteria, appropriate empirical antimicrobial therapy tailored to disease severity and risk factors, and consideration of adjunctive treatments such as corticosteroids in severe cases. Antimicrobial stewardship principles should guide therapy duration and de-escalation to minimize resistance and adverse effects. Preventive strategies, including vaccinations and lifestyle modifications, are essential to reduce the incidence of CAP and improve patient outcomes.

Reference: Vaughn VM, Dickson RP, Horowitz JK, Flanders SA. Community-Acquired Pneumonia: A Review. JAMA. Published online September 16, 2024. doi:10.1001/jama.2024.14796

 

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RCT: Preoxygenation with Noninvasive Ventilation Reduced Hypoxemia during Emergency Intubation

19 Sep, 2024 | 12:53h | UTC

Background: Hypoxemia during tracheal intubation in critically ill adults increases the risk of cardiac arrest and death. Preoxygenation aims to mitigate this risk, but the optimal method remains uncertain. Noninvasive ventilation (NIV) may offer advantages over oxygen masks by providing positive pressure and higher inspired oxygen fractions, but evidence is limited.

Objective: To determine whether preoxygenation with noninvasive ventilation reduces the incidence of hypoxemia during tracheal intubation compared to preoxygenation with an oxygen mask among critically ill adults.

Methods: In a multicenter, pragmatic, unblinded, randomized trial conducted at 24 emergency departments and intensive care units in the United States, 1301 critically ill adults (age ≥18 years) undergoing tracheal intubation were randomized 1:1 to receive preoxygenation with either noninvasive ventilation (n=645) or an oxygen mask (n=656). Patients already receiving positive-pressure ventilation or at high risk of aspiration were excluded. In the NIV group, preoxygenation was administered using a tight-fitting mask connected to a ventilator, with an FiO₂ of 100%, expiratory pressure ≥5 cm H₂O, and inspiratory pressure ≥10 cm H₂O. In the oxygen-mask group, preoxygenation was provided using a nonrebreather mask or bag-mask device without manual ventilation, with oxygen flow ≥15 liters per minute. The primary outcome was hypoxemia during intubation, defined as oxygen saturation <85% between induction of anesthesia and 2 minutes after tracheal intubation.

Results: Hypoxemia occurred in 9.1% of patients in the NIV group versus 18.5% in the oxygen-mask group (difference –9.4 percentage points; 95% CI, –13.2 to –5.6; P<0.001). Cardiac arrest during intubation occurred in 0.2% of patients in the NIV group and 1.1% in the oxygen-mask group (difference –0.9 percentage points; 95% CI, –1.8 to –0.1). Aspiration occurred in 0.9% of patients in the NIV group and 1.4% in the oxygen-mask group (difference –0.4 percentage points; 95% CI, –1.6 to 0.7). No significant differences were observed in other adverse events.

Conclusions: Preoxygenation with noninvasive ventilation significantly reduced the incidence of hypoxemia during tracheal intubation among critically ill adults compared to preoxygenation with an oxygen mask, without increasing the risk of aspiration.

Implications for Practice: Preoxygenation with noninvasive ventilation should be considered for critically ill adults undergoing emergency tracheal intubation to reduce the risk of hypoxemia and potential cardiac arrest. Clinicians should ensure appropriate equipment and training are available for the use of NIV during preoxygenation.

Study Strengths and Limitations: Strengths include a large sample size, multicenter design across diverse emergency departments and ICUs, and pragmatic approach enhancing generalizability. Limitations include exclusion of patients already receiving positive-pressure ventilation or at high risk of aspiration, potentially limiting applicability to these populations. The unblinded design may introduce bias, although outcome data were collected by independent observers.

Future Research: Further studies are needed to evaluate the effectiveness of noninvasive ventilation for preoxygenation in patients at high risk of aspiration and to compare its efficacy with high-flow nasal cannula. Research should also assess long-term clinical outcomes and cost-effectiveness of implementing NIV for preoxygenation.

Reference: Gibbs K.W., et al. (2024) Noninvasive Ventilation for Preoxygenation during Emergency Intubation. New England Journal of Medicine. DOI: http://doi.org/10.1056/NEJMoa2313680

 

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Meta-analysis: Perioperative Colchicine Reduced Postoperative Atrial Fibrillation After CABG

18 Sep, 2024 | 13:33h | UTC

Background: Coronary artery disease (CAD) remains a leading cause of mortality worldwide. Inflammation is a key factor in the development and progression of CAD, and anti-inflammatory therapies have shown potential in improving cardiovascular outcomes. Colchicine, traditionally used to treat gout, has demonstrated efficacy in reducing cardiovascular events in patients with chronic CAD. Previous individual studies have suggested that perioperative colchicine may decrease the incidence of postoperative atrial fibrillation (POAF) in patients undergoing coronary artery bypass grafting (CABG), but a comprehensive analysis is needed to confirm these findings.

Objective: To evaluate the effect of perioperative colchicine administration on the incidence of POAF in patients undergoing isolated CABG surgery through a meta-analysis of randomized controlled trials (RCTs).

Methods: A systematic search was conducted across MEDLINE, Web of Science, and The Cochrane Library to identify RCTs comparing perioperative colchicine administration with standard care in patients undergoing CABG. Inclusion criteria encompassed studies involving isolated CABG patients randomized to receive colchicine or standard care without colchicine. The primary outcome was the incidence of POAF during short-term follow-up.

Results: Five RCTs published between 2014 and 2022 met the inclusion criteria, including a total of 839 patients undergoing isolated CABG. Perioperative colchicine administration was associated with a significant reduction in POAF rates compared to standard care (relative risk [RR], 0.54; 95% confidence interval [CI], 0.40–0.73; p < 0.01). Other outcomes, such as graft patency, myocardial infarction, or long-term mortality, were not uniformly reported and, therefore, not analyzed.

Conclusions: Perioperative administration of colchicine is associated with a significant reduction in the incidence of POAF in patients undergoing CABG surgery.

Implications for Practice: Colchicine may be considered as a prophylactic strategy to reduce POAF in patients undergoing CABG, potentially improving both short- and long-term outcomes. Given the association of POAF with increased perioperative morbidity and long-term adverse events, implementing colchicine could have substantial clinical benefits in this high-risk population.

Study Strengths and Limitations: Strengths of this meta-analysis include the exclusive inclusion of randomized controlled trials and the use of rigorous statistical methods, including sensitivity analysis, which confirmed the robustness of the results. Limitations involve the small number of studies (five RCTs), potential variability in colchicine dosing regimens, and the lack of data on other clinically relevant outcomes.

Future Research: Large-scale, multicenter RCTs are warranted to further assess the effects of colchicine on other important outcomes in CABG patients, such as graft patency, myocardial infarction rates, and long-term mortality. Future studies should also evaluate the risk-benefit profile of colchicine in this patient population to establish its full role in clinical practice.

Reference: Kirov H., Caldonazo T., Runkel A., et al. (2024). Colchicine in Patients with Coronary Disease Undergoing Coronary Artery Bypass Surgery – A Meta-Analysis of Randomized Controlled Trials. The American Journal of Cardiology. DOI: http://doi.org/10.1016/j.amjcard.2024.09.003

 

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RCT: Stereotactic Body Radiotherapy Reduced Incontinence and Sexual Dysfunction vs. Prostatectomy in Localized Prostate Cancer

18 Sep, 2024 | 10:51h | UTC

Background: Men with localized prostate cancer have several treatment options, including prostatectomy and radiotherapy. Patient-reported outcomes (PROs) are crucial in guiding treatment decisions due to potential impacts on quality of life. However, randomized data comparing stereotactic body radiotherapy (SBRT) with prostatectomy are lacking.

Objective: To compare patient-reported urinary, bowel, and sexual outcomes at 2 years following SBRT versus prostatectomy in men with low- to intermediate-risk localized prostate cancer.

Methods: In the phase 3 PACE-A randomized controlled trial conducted in the UK from 2012 to 2022, 123 men with National Comprehensive Cancer Network (NCCN) low- to intermediate-risk localized prostate cancer were randomized 1:1 to receive either SBRT (36.25 Gy in five fractions) or prostatectomy. Androgen deprivation therapy was not permitted. The co-primary outcomes were the number of absorbent urinary pads used daily and the Expanded Prostate Index Composite (EPIC-26) bowel domain score at 2 years. Secondary outcomes included clinician-reported toxicity and sexual function.

Results: Among 110 men who received treatment (median age 65.5 years; median PSA 7.9 ng/ml; 92% intermediate-risk), 50 underwent prostatectomy and 60 received SBRT. At 2 years, 50% of prostatectomy patients reported using one or more urinary pads daily compared to 6.5% of SBRT patients (p < 0.001; difference 43%, 95% CI 25%–62%). Bowel domain scores were better for prostatectomy (median 100) than for SBRT (median 87.5; p < 0.001; mean difference 8.9, 95% CI 4.2–13.7). Sexual function scores were worse for prostatectomy (median 18) compared to SBRT (median 62.5; p < 0.001). Clinician-reported genitourinary and gastrointestinal toxicities were low in both groups.

Conclusions: SBRT was associated with significantly less urinary incontinence and sexual dysfunction but slightly worse bowel function compared to prostatectomy at 2 years in men with localized prostate cancer.

Implications for Practice: These findings provide preliminary evidence to inform treatment decisions for men with low- to intermediate-risk localized prostate cancer. SBRT may offer advantages in reducing urinary incontinence and sexual dysfunction, which are significant considerations for patients. Clinicians should also discuss the potential for increased bowel symptoms with SBRT.

Study Strengths and Limitations: Strengths include the randomized design, use of contemporary treatment modalities, and comprehensive assessment of PROs. Limitations involve the small sample size due to slow recruitment, differential dropout rates, and incomplete PRO responses at the 2-year mark.

Future Research: Larger-scale randomized trials are needed to confirm these findings, assess long-term outcomes beyond 2 years, and evaluate the impact on disease control and quality of life.

Reference: van As N, et al. Radical Prostatectomy Versus Stereotactic Radiotherapy for Clinically Localised Prostate Cancer: Results of the PACE-A Randomised Trial. European Urology. 2024. DOI: http://doi.org/10.1016/j.eururo.2024.08.030

 

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RCT: Twice-Yearly Depemokimab Reduced Exacerbations in Severe Eosinophilic Asthma

17 Sep, 2024 | 22:39h | UTC

Background: Severe asthma with an eosinophilic phenotype often leads to frequent exacerbations despite treatment with medium- or high-dose inhaled glucocorticoids and additional controllers. Interleukin-5 is pivotal in eosinophil growth and survival, contributing to airway inflammation. Existing biologic therapies targeting interleukin-5 require frequent dosing intervals. Depemokimab is an ultra-long-acting anti–interleukin-5 biologic with enhanced binding affinity, potentially allowing effective dosing every six months.

Objective: To evaluate the efficacy and safety of twice-yearly depemokimab in reducing exacerbations in patients with severe eosinophilic asthma.

Methods: Two multicenter, randomized, double-blind, placebo-controlled phase 3A trials (SWIFT-1 and SWIFT-2) were conducted. Patients aged ≥12 years with severe asthma and an eosinophilic phenotype (blood eosinophil count ≥300 cells/μL in the previous 12 months or ≥150 cells/μL at screening) and at least two exacerbations in the prior year despite medium- or high-dose inhaled glucocorticoids plus another controller were enrolled. Participants were randomized 2:1 to receive depemokimab 100 mg or placebo subcutaneously at weeks 0 and 26, alongside standard care. The primary endpoint was the annualized rate of exacerbations over 52 weeks. Secondary endpoints included changes from baseline in the St. George’s Respiratory Questionnaire (SGRQ) score, prebronchodilator FEV₁, and asthma symptom scores at 52 weeks.

Results: A total of 792 patients were randomized, with 762 included in the full analysis set (502 depemokimab, 260 placebo). In SWIFT-1, depemokimab significantly reduced the annualized exacerbation rate compared to placebo (0.46 vs 1.11; rate ratio 0.42; 95% CI, 0.30–0.59; P < .001). Similar results were observed in SWIFT-2 (0.56 vs 1.08; rate ratio 0.52; 95% CI, 0.36–0.73; P < .001). No significant between-group differences were found in change from baseline in SGRQ scores. The incidence of adverse events was similar between groups in both trials.

Conclusions: Twice-yearly administration of depemokimab significantly reduced the annualized rate of exacerbations in patients with severe eosinophilic asthma.

Implications for Practice: Depemokimab administered every six months may offer an effective treatment option for reducing exacerbations in severe eosinophilic asthma, potentially enhancing patient adherence and reducing treatment burden associated with more frequent dosing schedules.

Study Strengths and Limitations: Strengths include large, multicenter, randomized, placebo-controlled design and replicate trials confirming efficacy. Limitations involve the lack of significant improvement in quality-of-life measures, low exacerbation rates in the placebo group, potential impact of the COVID-19 pandemic on trial conduct and outcomes, and limited data on certain subpopulations.

Future Research: Further studies are needed to assess long-term safety and efficacy, effects on quality-of-life measures, and the role of depemokimab in broader asthma populations, including those with varying eosinophil counts and biomarker profiles.

Reference: Jackson DJ, et al. (2024) Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype. New England Journal of Medicine. DOI: http://doi.org/10.1056/NEJMoa2406673

 

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Systematic Review: Antidepressants Offer Limited Pain Relief with Potential Harms in Older Adults

17 Sep, 2024 | 11:34h | UTC

Background: Chronic pain is prevalent among older adults and significantly affects their quality of life. Antidepressants are commonly prescribed for pain management in this population across various countries. While several systematic reviews have evaluated the efficacy and safety of antidepressants for pain in adults, none have specifically focused on individuals aged 65 years and older. The efficacy and safety profile of antidepressants for pain relief in older adults remains unclear.

Objective: To assess the efficacy and safety of antidepressant medications compared to all alternatives for the management of non-cancer pain in older adults aged 65 years and above.

Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. Thirteen databases were searched from inception to February 1, 2024, to identify relevant studies. Trials included compared any antidepressant medication to any alternative (e.g., placebo, other medications, or non-drug therapies) for the treatment of non-cancer pain in older adults. Data extracted included study and participant characteristics, primary efficacy outcomes (pain scores converted to a 0–100 scale), and harms. Estimates for efficacy were pooled using a random-effects model and reported as mean differences with 95% confidence intervals (CIs). The quality of included trials was assessed using the Cochrane risk of bias tool.

Results: Fifteen studies encompassing 1,369 participants met the inclusion criteria. The most frequently studied antidepressants were duloxetine and amitriptyline (six studies each). Pain related to knee osteoarthritis was the most commonly studied condition (six studies). For knee osteoarthritis:

• Immediate Term (0–2 weeks): Antidepressants did not provide a statistically significant reduction in pain compared to alternatives (mean difference [MD], –5.6; 95% CI, –11.5 to 0.3).
• Intermediate Term (≥6 weeks and <12 months): Duloxetine provided a statistically significant, albeit very small, reduction in pain (MD, –9.1; 95% CI, –11.8 to –6.4).

Nearly half of the studies (7 out of 15) reported increased withdrawal of participants in the antidepressant treatment group compared to the comparator group due to adverse events.

Conclusions: For most chronic painful conditions in older adults, the benefits and harms of antidepressant medications are unclear. The available evidence predominantly comes from trials with small sample sizes (less than 100 participants), disclosed industry ties, and trials classified as having unclear or high risk of bias.

Implications for Practice:

• Minimal Benefit: Antidepressants, particularly duloxetine, may offer a very small benefit for pain relief in older adults with knee osteoarthritis over the intermediate term.
• Risk of Harms: The potential harms, including increased adverse events leading to higher withdrawal rates, may outweigh these minimal benefits.
• Clinical Decision-Making: Clinicians should carefully weigh the benefits against the risks when considering prescribing antidepressants for pain in older adults.
• Alternative Strategies: Non-pharmacological interventions and alternative pain management strategies should be prioritized in this population.

Study Strengths and Limitations: Strengths include the comprehensive search strategy across multiple databases and the focus on older adults, a population often underrepresented in clinical trials. Limitations involve the generally low quality of the included trials, small sample sizes, high risk of bias, and inconsistent reporting of pain outcomes and adverse events among studies.

Future Research: Further large-scale, high-quality randomized controlled trials are needed to investigate the efficacy and safety of antidepressants for pain management in older adults. Future studies should also compare antidepressants to non-pharmacological interventions and explore long-term outcomes and optimal dosing regimens in this population.

Reference: Narayan SW, Naganathan V, Vizza L, et al. Efficacy and Safety of Antidepressants for Pain in Older Adults: A Systematic Review and Meta-Analysis. Br J Clin Pharmacol. Published online September 12, 2024. doi:10.1111/bcp.16234

 

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