Daily Archives: November 16, 2024
Cohort Study: High Rate of Preventable Adverse Events in Surgical Inpatients
16 Nov, 2024 | 17:29h | UTCBackground: Adverse events during hospital admissions, particularly in surgical settings, remain a significant cause of patient harm despite efforts to improve patient safety since the “To Err is Human” report. Advances in surgical techniques and patient care necessitate an updated assessment of the current state of perioperative safety.
Objective: To estimate the frequency, severity, and preventability of adverse events associated with perioperative care in surgical inpatients and to identify the settings and healthcare professionals involved.
Methods: A multicenter retrospective cohort study was conducted across 11 US hospitals in Massachusetts. A weighted random sample of 1,009 patients was selected from 64,121 adults admitted for surgery in 2018. Trained nurses reviewed electronic health records to identify adverse events, which were then adjudicated by physicians. Adverse events were classified by type, severity, preventability, setting, and professions involved.
Results: Adverse events occurred in 38.0% of patients (95% CI, 32.6–43.4%), with major adverse events in 15.9% (12.7–19.0%). Among 593 adverse events identified, 59.5% were potentially preventable, and 20.7% were definitely or probably preventable. The most common events were surgery-related (49.3%), adverse drug events (26.6%), healthcare-associated infections (12.4%), and patient care events (11.2%). Adverse events most frequently occurred in general care units (48.8%) and involved attending physicians (89.5%) and nurses (58.9%).
Conclusions: More than one-third of surgical inpatients experienced adverse events, with nearly half classified as major and most potentially preventable. These findings highlight the critical need for ongoing improvement in patient safety throughout perioperative care involving all healthcare professionals.
Implications for Practice: Healthcare providers should enhance patient safety protocols across all perioperative settings, not just in operating rooms. Emphasis should be placed on preventing surgery-related complications, adverse drug events, and healthcare-associated infections by fostering teamwork and continuous monitoring.
Study Strengths and Limitations: Strengths include a comprehensive review of medical records and systematic classification of adverse events by trained professionals. Limitations involve the study’s confinement to Massachusetts hospitals in 2018, potential variability in documentation practices, and limited sample size affecting generalizability and specialty-specific estimates.
Future Research: Further studies are needed to assess adverse event rates in diverse geographic locations and healthcare systems, explore effective interventions to reduce preventable harm, and evaluate long-term trends in surgical patient safety.
RCT: Intensive Systolic Blood Pressure Target Reduces Cardiovascular Events in Type 2 Diabetes
16 Nov, 2024 | 16:49h | UTCBackground: Patients with type 2 diabetes frequently have elevated systolic blood pressure, heightening their risk for cardiovascular disease. Optimal systolic blood-pressure targets in this population remain unclear due to inconclusive results from previous trials.
Objective: To determine whether intensive treatment targeting a systolic blood pressure of less than 120 mm Hg reduces major cardiovascular events compared to standard treatment targeting less than 140 mm Hg in patients with type 2 diabetes.
Methods: In this randomized controlled trial conducted at 145 sites in China, 12,821 patients aged 50 or older with type 2 diabetes, elevated systolic blood pressure, and increased cardiovascular risk were assigned to intensive treatment (target <120 mm Hg) or standard treatment (target <140 mm Hg). The primary outcome was a composite of nonfatal stroke, nonfatal myocardial infarction, treatment or hospitalization for heart failure, or death from cardiovascular causes.
Results: Over a median follow-up of 4.2 years, the intensive-treatment group achieved a mean systolic blood pressure of 121.6 mm Hg versus 133.2 mm Hg in the standard-treatment group at 1 year. Primary outcome events occurred in 393 patients in the intensive group (1.65 events per 100 person-years) versus 492 patients in the standard group (2.09 events per 100 person-years) (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.69 to 0.90; P<0.001). Serious adverse events were similar between groups, but symptomatic hypotension and hyperkalemia were more frequent in the intensive-treatment group.
Conclusions: Intensive systolic blood-pressure control to less than 120 mm Hg significantly reduced major cardiovascular events in patients with type 2 diabetes compared to standard treatment.
Implications for Practice: These findings support adopting more aggressive systolic blood-pressure targets in patients with type 2 diabetes to prevent cardiovascular events. Clinicians should balance the benefits with potential risks, monitoring for hypotension and hyperkalemia.
Study Strengths and Limitations: Strengths include a large sample size, multicenter design, and sufficient power to detect differences in cardiovascular outcomes. Limitations involve unblinded treatment assignment, which may introduce bias, and reliance on self-reported home blood-pressure measurements during the COVID-19 pandemic, potentially affecting data accuracy. The exclusive enrollment of Chinese patients may limit generalizability to other populations. The increased incidence of hypotension and hyperkalemia raises concerns about the safety of intensive blood-pressure lowering in broader practice.
Future Research: Further studies should assess the long-term safety and efficacy of intensive blood-pressure control in diverse populations and explore strategies to minimize adverse events. Investigations into personalized blood-pressure targets based on patient characteristics may enhance clinical outcomes.
RCT: Tirzepatide Reduces Heart Failure Events and Improves Health Status in Obese HFpEF Patients
16 Nov, 2024 | 16:42h | UTCBackground: Obesity significantly increases the risk of heart failure with preserved ejection fraction (HFpEF) due to visceral adiposity-induced systemic inflammation affecting the myocardium. Tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, induces substantial weight loss. However, its effects on cardiovascular outcomes in obese HFpEF patients were previously unknown.
Objective: To assess the impact of tirzepatide on cardiovascular events and health status in patients with HFpEF and obesity.
Methods: In this international, double-blind, randomized, placebo-controlled trial, 731 patients with HFpEF (ejection fraction ≥50%), a body-mass index (BMI) of at least 30, and New York Heart Association class II–IV symptoms were assigned to receive tirzepatide (up to 15 mg subcutaneously once weekly) or placebo for at least 52 weeks. The two primary endpoints were the composite of adjudicated death from cardiovascular causes or worsening heart-failure events, and the change from baseline to 52 weeks in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS).
Results: Over a median follow-up of 104 weeks, death from cardiovascular causes or worsening heart-failure events occurred in 9.9% of patients in the tirzepatide group versus 15.3% in the placebo group (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.41 to 0.95; P=0.026). Worsening heart-failure events occurred in 8.0% with tirzepatide versus 14.2% with placebo (HR, 0.54; 95% CI, 0.34 to 0.85). At 52 weeks, the mean increase in KCCQ-CSS was 19.5 points in the tirzepatide group compared to 12.7 points in the placebo group (between-group difference, 6.9; 95% CI, 3.3 to 10.6; P<0.001). Adverse events leading to discontinuation occurred in 6.3% of tirzepatide patients versus 1.4% of placebo patients, mainly due to gastrointestinal symptoms.
Conclusions: Tirzepatide significantly reduced the risk of cardiovascular death or worsening heart failure and improved health status in patients with HFpEF and obesity.
Implications for Practice: These findings suggest that tirzepatide may be an effective therapeutic option for reducing heart failure events and enhancing quality of life in obese patients with HFpEF. Its benefits may be attributed to significant weight loss and anti-inflammatory effects, offering a potential new approach in managing this patient population.
Study Strengths and Limitations: Strengths include the randomized, double-blind design and a long median follow-up of 104 weeks. Limitations involve the exclusion of patients with BMI less than 30, which may limit applicability to non-obese HFpEF patients with increased visceral adiposity. Additionally, the higher rate of gastrointestinal adverse events leading to discontinuation in the tirzepatide group warrants cautious consideration.
Future Research: Further studies are needed to evaluate tirzepatide’s effects in HFpEF patients with lower BMI but increased visceral adiposity and to elucidate the mechanisms underlying its cardiovascular benefits.
Retrospective Cohort Study: Midline Catheters Associated with Lower Major Complications Than PICCs in Outpatient Antimicrobial Therapy
16 Nov, 2024 | 14:35h | UTCBackground: Outpatient parenteral antimicrobial therapy (OPAT) requires reliable vascular access for administering intravenous antibiotics post-hospitalization. Peripherally inserted central catheters (PICCs) are commonly used due to their versatility and ease of placement. Recently, midline catheters have emerged as potential alternatives for OPAT, offering less invasive access. However, limited evidence exists comparing the safety and complication rates of midline catheters versus PICCs in OPAT patients.
Objective: To compare the risk of major and minor device complications associated with midline catheters versus PICCs in patients receiving OPAT.
Methods: This retrospective cohort study analyzed data from 2,824 hospitalized patients across 69 Michigan hospitals who received either a midline catheter (n=1,999) or a PICC (n=825) for OPAT between January 2017 and November 2023. Patients receiving vancomycin were excluded. The primary outcome was major device complications, defined as catheter-related bloodstream infection (CRBSI) or catheter-related venous thromboembolism (CR-VTE). Secondary outcomes included minor device complications (e.g., catheter dislodgement, occlusion) and device failure, defined as catheter removal due to any complication.
Results: Midline catheters were associated with a lower risk of major complications compared to PICCs (0.8% vs 3.4%; adjusted hazard ratio [aHR], 0.46; 95% CI, 0.23-0.91; P < .001). This difference was more pronounced for devices with dwell times of 14 days or fewer (aHR, 0.29; 95% CI, 0.12-0.68). There were no significant differences in minor complications (10.3% vs 13.8%; aHR, 1.07; 95% CI, 0.83-1.38) or device failure rates (9.6% vs 12.1%; aHR, 1.26; 95% CI, 0.96-1.65) between midline catheters and PICCs.
Conclusions: Midline catheters are associated with a lower risk of major complications compared to PICCs in patients receiving OPAT, particularly for treatment durations of 14 days or fewer. These findings suggest that midline catheters are a safe and effective alternative to PICCs for short-term OPAT.
Implications for Practice: Clinicians should consider using midline catheters for OPAT when the anticipated therapy duration is 14 days or less and the infusate is peripherally compatible. This may reduce the risk of major complications such as CRBSI and CR-VTE, potentially improving patient outcomes and reducing healthcare costs.
Study Strengths and Limitations: Strengths of this study include a large, diverse patient population across multiple hospitals and rigorous data collection methods. Limitations include its retrospective design, potential for unmeasured confounding, and exclusion of patients receiving vancomycin, which may limit generalizability. Additionally, complications occurring after 30 days or post-device removal may have been missed.
Future Research: Further studies are needed to evaluate the safety and efficacy of midline catheters for OPAT durations exceeding 14 days and to explore factors influencing long-term device performance and patient outcomes.
Test-Negative Study: RSV Vaccine May Reduce Hospitalizations and ED Visits in Adults Aged ≥60
16 Nov, 2024 | 14:18h | UTCBackground: Respiratory syncytial virus (RSV) is a significant cause of morbidity and mortality among older adults in the USA, with an estimated 100,000–160,000 RSV-associated hospitalizations annually in those aged 60 years and older. In 2023, RSV vaccines were recommended for this population, showing efficacy in clinical trials. However, real-world effectiveness data, particularly against severe outcomes like hospitalizations in high-risk groups, are limited.
Objective: To assess the real-world effectiveness of RSV vaccination against RSV-associated hospitalizations and emergency department (ED) encounters among adults aged 60 years and older during the 2023–24 RSV season in the USA.
Methods: A test-negative design analysis was conducted using data from the Virtual SARS-CoV-2, Influenza, and Other Respiratory Viruses Network (VISION), encompassing eight states. Adults aged ≥60 presenting with RSV-like illness and tested for RSV from Oct 1, 2023, to Mar 31, 2024, were included. Vaccination status was determined through electronic health records, immunization registries, and medical claims. Vaccine effectiveness (VE) was estimated by comparing the odds of vaccination among RSV-positive cases and RSV-negative controls, adjusting for age, sex, race and ethnicity, comorbidities, and geographic region.
Results: Among 28,271 hospitalizations for RSV-like illness in immunocompetent adults aged ≥60, VE against RSV-associated hospitalization was 80% (95% CI 71–85). VE against RSV-associated critical illness (ICU admission or death) was 81% (95% CI 52–92). In 8,435 hospitalizations among immunocompromised adults, VE was 73% (95% CI 48–85) against RSV-associated hospitalization. Among 36,521 ED encounters in immunocompetent adults, VE against RSV-associated ED visits was 77% (95% CI 70–83). VE estimates were consistent across age groups and vaccine products.
Conclusions: RSV vaccination effectively prevented RSV-associated hospitalizations and ED visits among adults aged ≥60 during the first season post-approval, including those at highest risk due to advanced age or immunocompromise.
Implications for Practice: These findings support recommending RSV vaccination for adults aged ≥60 to reduce severe RSV-related morbidity and mortality. Clinicians should consider advising eligible patients to receive the RSV vaccine to prevent hospitalizations and critical illness.
Study Strengths and Limitations: Strengths include a large, geographically diverse cohort and integrated medical, laboratory, and vaccination data, allowing robust VE estimates across subgroups. Limitations involve potential misclassification of vaccination status, residual confounding, and reliance on clinician-directed RSV testing, which may introduce bias.
Future Research: Further studies are needed to evaluate the duration of vaccine protection over multiple RSV seasons and to assess VE in other high-risk populations and settings.
Phase 3 RCT: Resmetirom Significantly Improves NASH Resolution and Liver Fibrosis
16 Nov, 2024 | 13:56h | UTCBackground: Nonalcoholic steatohepatitis (NASH) is a progressive liver disease with no approved treatments. It significantly increases the risk of liver-related complications, especially in patients with type 2 diabetes. Resmetirom, a thyroid hormone receptor beta-selective agonist, is being investigated for its potential to treat NASH and liver fibrosis.
Objective: To evaluate the efficacy and safety of resmetirom in resolving NASH and improving fibrosis in adults with biopsy-confirmed NASH and fibrosis stages F1B to F3.
Methods: This double-blind, placebo-controlled phase 3 trial randomized 966 adults with NASH to receive once-daily resmetirom (80 mg or 100 mg) or placebo for 52 weeks. Primary endpoints included (1) NASH resolution with no fibrosis worsening and (2) fibrosis improvement by at least one stage without NAFLD activity score worsening. Secondary outcomes included changes in lipid profiles and liver biomarkers.
Results: At 52 weeks, NASH resolution occurred in 25.9% of patients receiving 80 mg and 29.9% receiving 100 mg of resmetirom, compared with 9.7% in the placebo group (P<0.001 for both doses vs. placebo). Fibrosis improved by at least one stage in 24.2% (80 mg) and 25.9% (100 mg) of resmetirom-treated patients versus 14.2% for placebo (P<0.001). LDL cholesterol reductions were −13.6% (80 mg) and −16.3% (100 mg) at 24 weeks versus 0.1% for placebo (P<0.001). Improvements were also noted in triglycerides, liver enzymes, and imaging biomarkers. Adverse events, primarily mild gastrointestinal symptoms, were more frequent with resmetirom. Serious adverse events were similar across groups (10.9%–12.7%).
Conclusions: Resmetirom significantly improved NASH resolution and fibrosis compared to placebo, demonstrating its potential as a treatment for NASH with liver fibrosis.
Implications for Practice: Resmetirom offers a promising treatment option for NASH, potentially altering the disease course and improving outcomes. Clinicians should monitor for regulatory approval and long-term safety data.
Study Strengths and Limitations: Strengths include robust biopsy-confirmed endpoints and a large sample size. Limitations include short follow-up and lack of clinical-outcome data.
Future Research: Long-term studies are needed to assess durability, safety, and effects on clinical outcomes like cirrhosis and liver-related mortality.
RCT: Once-Weekly Semaglutide Reduces Weight and Knee Osteoarthritis Pain in Obese Patients
16 Nov, 2024 | 13:41h | UTCBackground: Obesity is a major risk factor for the development and progression of knee osteoarthritis, leading to chronic pain and reduced mobility. Weight reduction has been shown to alleviate symptoms, but sustained, non-surgical interventions are limited. Glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide, have demonstrated efficacy in weight management; however, their impact on knee osteoarthritis pain is not well established.
Objective: To assess the efficacy of once-weekly subcutaneous semaglutide (2.4 mg) versus placebo, alongside lifestyle interventions, on body weight reduction and pain related to knee osteoarthritis in adults with obesity.
Methods: In this 68-week, double-blind, randomized, placebo-controlled trial conducted at 61 sites across 11 countries, 407 adults with obesity (BMI ≥30) and moderate knee osteoarthritis with at least moderate pain were enrolled. Participants were randomized in a 2:1 ratio to receive semaglutide or placebo, in addition to counseling on a reduced-calorie diet and increased physical activity. The primary endpoints were the percentage change in body weight and the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score from baseline to week 68.
Results: Semaglutide treatment resulted in a mean weight reduction of −13.7% compared to −3.2% with placebo (P<0.001). The mean change in WOMAC pain score was −41.7 points with semaglutide versus −27.5 points with placebo (P<0.001), indicating a significant reduction in pain. Additionally, semaglutide led to greater improvements in physical function scores and a decrease in the use of nonsteroidal anti-inflammatory drugs. Serious adverse events were similar between groups; however, gastrointestinal disorders led to more discontinuations in the semaglutide group (6.7% vs. 3.0%).
Conclusions: Once-weekly subcutaneous semaglutide significantly reduces body weight and alleviates pain related to knee osteoarthritis in obese adults, compared to placebo, when combined with lifestyle modifications. These findings support semaglutide as an effective non-surgical intervention for weight management and symptom relief in this population.
Implications for Practice: Semaglutide may be considered as part of a comprehensive treatment strategy for obese patients with knee osteoarthritis, potentially improving pain, physical function, and reducing reliance on analgesics. Clinicians should weigh the benefits against potential gastrointestinal side effects.
Study Strengths and Limitations: Strengths include the randomized, double-blind design and a sizable, diverse cohort. Limitations involve the absence of imaging follow-up, lack of metabolic and inflammatory marker assessments, and no post-treatment outcome data to evaluate the sustainability of benefits after discontinuation.
Future Research: Further studies are warranted to explore the long-term effects of semaglutide on knee osteoarthritis progression, its mechanisms of action on joint pathology, and its effectiveness in broader patient populations.
Review: Lung Transplantation
16 Nov, 2024 | 13:33h | UTCIntroduction: Lung transplantation has progressed from experimental to standard therapy for life-threatening lung diseases, offering improved survival and quality of life. Challenges include primary graft dysfunction, chronic lung allograft dysfunction (CLAD), infections, and long-term immunosuppression effects. This review highlights current practices, developments, and opportunities to enhance this transformative therapy.
Key Recommendations
- Candidate Selection: Selection criteria have shifted from strict contraindications to a holistic approach emphasizing physiologic age, frailty, and recoverability. Early referral and multidisciplinary assessment are recommended to address barriers and optimize outcomes.
- Donor-Lung Utilization: Extended-criteria donors, including older donors and those with smoking histories, are increasingly used. Ex vivo lung perfusion allows detailed lung assessment and reconditioning, while antiviral therapies enable transplantation of lungs from hepatitis C-positive donors.
- Lung Allocation: Urgency-weighted scores prioritize factors like medical urgency and post-transplant survival. Recent updates include biologic disadvantages, patient access, and logistical efficiency to improve fairness and outcomes.
- Surgical Techniques: Bilateral sequential lung transplantation is standard, with ECMO replacing cardiopulmonary bypass in many cases. Surgical approaches are tailored to individual needs, with options like volume reduction or lobectomy for size mismatches.
- Postoperative Management: Primary graft dysfunction affects up to 25% of recipients and is a major early complication. Preventive strategies, ECMO support, and infection management are critical. Attention to airway complications and acute kidney injury further improves recovery.
- Immunosuppression: Maintenance therapy typically includes a calcineurin inhibitor, glucocorticoid, and cell-cycle inhibitor. Induction therapy is individualized. Ongoing studies are exploring adjunct therapies like mTOR inhibitors and inhaled immunosuppressants to prevent CLAD.
- Management of ALAD and CLAD: Early detection and treatment of acute lung allograft dysfunction are essential. CLAD, affecting half of recipients within 5 years, remains a major challenge. Current therapies slow progression, but further research is needed for targeted prevention and treatment.
- Infections: Infections remain a leading cause of morbidity and mortality. Prophylaxis against cytomegalovirus, fungal pathogens, and community-acquired viruses is essential to minimize complications and reduce CLAD risk.
- Cancer Risk: Post-transplant cancer risk is elevated due to immunosuppression. Lung cancer and post-transplant lymphoproliferative disease are the most common malignancies, emphasizing the need for routine surveillance and early intervention.
- Long-Term Outcomes: Median survival remains limited at 6.7 years. Efforts focus on improving long-term outcomes by balancing graft function maintenance with minimizing adverse effects of immunosuppression. Collaborative research aims to refine diagnostics, personalize therapies, and address CLAD mechanisms.
Conclusion: Enhanced donor utilization, tailored candidate selection, refined perioperative care, and robust long-term monitoring are pivotal to advancing lung transplantation. Ongoing research and collaboration are critical to overcoming challenges like CLAD, improving survival, and enhancing patient quality of life.