Daily Archives: August 18, 2024
Meta-Analysis: ERAS Protocols Improve Recovery and Reduce Complications After Emergency Laparotomy – Am J Surg
18 Aug, 2024 | 19:32h | UTCStudy Design and Population: This systematic review and meta-analysis assessed the effects of Enhanced Recovery After Surgery (ERAS) protocols compared to standard care (SC) in patients undergoing emergency laparotomy. The analysis included six randomized clinical trials (RCTs) with a total of 509 patients.
Main Findings: The ERAS group showed a reduction in length of hospital stay (mean difference: -2.92 days) and quicker recovery milestones, such as time to ambulation (mean difference: -1.67 days) and first bowel opening (mean difference: -1.26 days). The ERAS protocols were also associated with lower rates of pulmonary complications (odds ratio [OR]: 0.43) and surgical site infections (OR: 0.33). Mortality rates were similar between the ERAS and SC groups.
Implications for Practice: These findings suggest that ERAS protocols may enhance recovery and reduce complications in patients undergoing emergency laparotomy. Implementation of these protocols could be beneficial in emergency surgical settings, where feasible.
Systematic Review: Nasogastric Feeding Increases Diarrhea and Pain Compared to Nasojejunal Feeding in Acute Pancreatitis – BMC Gastroenterol
18 Aug, 2024 | 19:23h | UTCStudy Design and Population: This systematic review and meta-analysis compared the safety and efficacy of nasogastric (NG) versus nasojejunal (NJ) feeding initiated within 48 hours of hospital admission in patients with moderate to severe acute pancreatitis. The analysis included four randomized controlled trials (RCTs) involving a total of 217 patients.
Main Findings: The review found no significant difference in mortality between NG and NJ feeding groups. However, NG feeding was associated with a higher incidence of diarrhea (RR 2.75, P = 0.02) and pain (RR 2.91, P = 0.002). The risk of infection was also higher in the NG group (6.67% vs. 3.33%, P = 0.027). No significant differences were observed in the need for surgical intervention, the requirement for parenteral nutrition, or the success rates of feeding procedures.
Implications for Practice: The findings suggest that while NG feeding does not increase mortality in acute pancreatitis, it is associated with higher rates of certain complications, particularly diarrhea and pain. Clinicians should consider these risks when choosing a feeding strategy for patients with acute pancreatitis, especially within the critical early 48-hour period post-admission.
Cohort Study: One-Fourth of MS Relapses Occur Without MRI Activity, Highlighting ACES Phenomenon – JAMA Neurol
18 Aug, 2024 | 19:16h | UTCStudy Design and Population: This multicenter observational cohort study examined 637 clinical relapse events in 608 patients with relapsing-remitting multiple sclerosis (RRMS) from the French MS registry, spanning January 2015 to June 2023. The study included relapses with brain and spinal cord MRI performed within 12-24 months before and 50 days after the event.
Main Findings: Approximately 26% of relapses were classified as acute clinical events with stable MRI (ACES), showing no new T2 or gadolinium-enhanced T1 lesions. ACES were more likely in patients on highly effective disease-modifying therapies (DMTs), with longer disease duration, or with fatigue. ACES were associated with increased rates of relapse, confirmed disability accrual, and progression to secondary progressive MS, though their MRI stability was unaffected by DMTs.
Implications for Practice: The study suggests that MRI alone may not fully capture disease activity in RRMS, highlighting the need for comprehensive clinical assessment in therapeutic decision-making and clinical trial designs.
RCT: Chelation Fails to Reduce Cardiovascular Events in Post-MI Patients with Diabetes – JAMA
18 Aug, 2024 | 19:11h | UTCStudy Design and Population: This double-masked, placebo-controlled randomized clinical trial (RCT) included 959 participants aged 50 or older with diabetes and a history of myocardial infarction (MI) from 88 sites in the US and Canada. Participants were randomly assigned to receive either 40 weekly infusions of an EDTA-based chelation solution or a placebo infusion. The median follow-up period was 48 months.
Main Findings: The trial found no significant reduction in major adverse cardiovascular events (MACE) with EDTA-based chelation compared to placebo. The primary endpoint, a composite of all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for unstable angina, occurred in 35.6% of the chelation group and 35.7% of the placebo group (HR, 0.93; 95% CI, 0.76-1.16; P = .53). However, chelation did reduce median blood lead levels by 61%, from 9.0 μg/L at baseline to 3.5 μg/L by the 40th infusion (P < .001).
Implications for Practice: Despite the significant reduction in blood lead levels, EDTA-based chelation did not reduce cardiovascular events in this high-risk population. These findings suggest that while chelation therapy may lower lead levels, it does not translate into cardiovascular benefits for patients with diabetes and a history of MI, challenging its use in this context.
RCT: Belantamab Mafodotin Combination Improves Progression-Free Survival in Relapsed/Refractory Multiple Myeloma Compared to Daratumumab-Based Therapy – N Engl J Med
18 Aug, 2024 | 19:03h | UTCStudy Design and Population: This phase 3, open-label, randomized controlled trial compared the efficacy and safety of belantamab mafodotin, bortezomib, and dexamethasone (BVd) versus daratumumab, bortezomib, and dexamethasone (DVd) in 494 patients with relapsed or refractory multiple myeloma after at least one prior therapy. Patients were randomly assigned to the BVd group (243) or the DVd group (251) and were followed for a median of 28.2 months.
Main Findings: The BVd regimen significantly improved median progression-free survival (36.6 months vs. 13.4 months; HR, 0.41; P<0.001) compared to the DVd regimen. Overall survival at 18 months was also higher in the BVd group (84% vs. 73%). The BVd group showed a higher rate of complete response or better plus MRD-negative status (25% vs. 10%). However, the BVd regimen was associated with a higher incidence of grade 3 or higher adverse events (95% vs. 78%), particularly ocular events.
Implications for Practice: BVd therapy offers a significant progression-free survival advantage over DVd in patients with relapsed or refractory multiple myeloma, though it is associated with a higher rate of serious adverse events, particularly ocular toxicity. These findings suggest BVd as a potent treatment option but highlight the need for careful monitoring and management of side effects, particularly eye-related complications.
Retrospective Cohort Study: Rheumatoid Arthritis Linked to Over 50% Increased Lung Cancer Risk, with a Three-Fold Risk in RA-Associated Interstitial Lung Disease – Arthritis Rheumatol
18 Aug, 2024 | 18:58h | UTCStudy Design and Population: This retrospective matched cohort study examined the risk of lung cancer in 72,795 patients with rheumatoid arthritis (RA) and 757 patients with RA-associated interstitial lung disease (RA-ILD) from the Veterans Health Administration database, compared with 633,937 non-RA controls. The study spanned from 2000 to 2019, with patients matched on age, gender, and enrollment year.
Main Findings: The study found that RA was associated with a 58% increase in lung cancer risk (adjusted hazard ratio [aHR] 1.58). The risk was significantly higher in RA-ILD patients, with a more than three-fold increase (aHR 3.25) compared to non-RA controls. Even among never smokers, RA patients showed a 65% increased lung cancer risk, indicating that factors beyond smoking contribute to the elevated risk.
Implications for Practice: The study underscores the significant increase in lung cancer risk among patients with RA, particularly those with RA-ILD. While this elevated risk is notable, further research is necessary to determine the most effective strategies for monitoring and managing this risk. Clinicians should be aware of these findings and consider them when evaluating the overall health and risk factors of patients with RA, especially those with additional pulmonary complications like ILD. Enhanced awareness and individualized risk assessments may help in early detection and management of lung cancer in this high-risk population.
Randomized Noninferiority Trial: Oral Vonoprazan Noninferior to IV Proton Pump Inhibitors in Preventing Rebleeding of High-Risk Peptic Ulcers – Gastroenterology
18 Aug, 2024 | 18:32h | UTCStudy Design and Population: This multicenter, randomized, open-label, noninferiority trial was conducted in Thailand across six centers, including both university and community hospitals. A total of 194 patients with high-risk peptic ulcer (PU) bleeding who had achieved successful endoscopic hemostasis were randomized to receive either vonoprazan or intravenous proton pump inhibitors (PPI). The study aimed to compare the efficacy of vonoprazan, a potassium-competitive acid blocker, with that of high-dose PPIs in preventing rebleeding.
Main Findings: The trial found that the 30-day rebleeding rate in the vonoprazan group was 7.1%, compared to 10.4% in the PPI group. This demonstrated noninferiority of vonoprazan within a 10% margin (risk difference: -3.3%, 95% CI: -11.2 to 4.7; P < .001). The 3-day and 7-day rebleeding rates were also noninferior. Secondary outcomes, including mortality rates, the need for rescue therapy, blood transfusion requirements, and length of hospital stay, were comparable between the two groups. Adverse events were similar in both groups.
Implications for Practice: Vonoprazan presents a viable alternative to intravenous PPIs for preventing rebleeding in patients with high-risk PU after endoscopic hemostasis. The availability of vonoprazan in oral form could potentially reduce hospital stays. However, further studies in multiethnic populations are needed to confirm these findings and assess the cost-effectiveness of vonoprazan in this setting.
RCT: Atezolizumab with Chemotherapy Extends Progression-Free Survival in dMMR Advanced Endometrial Cancer – Lancet Oncol
18 Aug, 2024 | 18:27h | UTCStudy Design and Population: The AtTEnd trial is a randomized, double-blind, placebo-controlled phase 3 study conducted in 89 hospitals across 11 countries. It enrolled 551 patients with advanced or recurrent endometrial carcinoma or carcinosarcoma, all of whom had not received prior systemic chemotherapy for recurrence.
Main Findings: The addition of atezolizumab to chemotherapy was associated with an improvement in progression-free survival, particularly in patients with mismatch repair-deficient (dMMR) tumors. In the overall population, progression-free survival and overall survival also showed positive trends.
Implications for Practice: The study suggests that atezolizumab may offer benefits when added to standard chemotherapy in patients with dMMR advanced or recurrent endometrial carcinoma, warranting further investigation as a potential first-line treatment option.
Non-Inferiority Trial: Burr-Hole Drainage Without Irrigation Results in Higher Reoperation Rate in Chronic Subdural Hematoma – The Lancet
18 Aug, 2024 | 18:17h | UTCStudy Design and Population: This Finnish, nationwide, multicentre, randomised, controlled non-inferiority trial (FINISH) evaluated whether subdural irrigation during burr-hole drainage for chronic subdural haematoma could be omitted without compromising outcomes. The trial enrolled 589 adults (165 women, 424 men) requiring burr-hole drainage, randomly assigned to receive drainage with or without irrigation.
Main Findings: The study found a 6.0 percentage point higher reoperation rate within 6 months in the non-irrigation group (18.3%) compared to the irrigation group (12.6%). There were no significant differences in secondary outcomes, including the proportion of patients with an unfavorable functional outcome (13.1% vs. 12.6%) or mortality (6.1% vs. 7.1%). Adverse events were comparable between the groups.
Implications for Practice: The trial results suggest that omitting subdural irrigation during burr-hole drainage increases the risk of reoperation, without improving functional outcomes or reducing mortality. The findings support the continued use of subdural irrigation in this procedure.
RCT: Isatuximab Plus VRd Significantly Improves Progression-Free Survival in Newly Diagnosed Multiple Myeloma – N Engl J Med
18 Aug, 2024 | 18:11h | UTCStudy Design and Population: This international, open-label, phase 3 trial assessed the efficacy of adding isatuximab to the bortezomib, lenalidomide, and dexamethasone (VRd) regimen in 446 patients aged 18 to 80 years with newly diagnosed multiple myeloma who were ineligible for transplantation. Participants were randomized in a 3:2 ratio to receive either the isatuximab-VRd combination or VRd alone.
Main Findings: At a median follow-up of 59.7 months, the isatuximab-VRd group showed a significantly higher estimated progression-free survival at 60 months (63.2% vs. 45.2%; HR, 0.60; P<0.001) compared to the VRd group. Additionally, the isatuximab-VRd group had higher rates of complete response or better (74.7% vs. 64.1%; P=0.01) and MRD-negative status with a complete response (55.5% vs. 40.9%; P=0.003). Safety profiles were comparable between the two groups.
Implications for Practice: The addition of isatuximab to the standard VRd regimen significantly improves progression-free survival and response rates in newly diagnosed multiple myeloma patients who are ineligible for transplantation, without increasing serious adverse events. This suggests that isatuximab-VRd may be considered a new standard of care in this patient population.
Cohort Study: Prenatal Exposure to Buprenorphine with Naloxone Appears Safe and More Effective than Buprenorphine Alone for Neonates and Mothers – JAMA
18 Aug, 2024 | 18:06h | UTCStudy Design and Population: This population-based cohort study used healthcare data from Medicaid-insured pregnancies in the US between 2000 and 2018. The study included 8,695 pregnant individuals linked to their liveborn infants. Participants were exposed to either buprenorphine combined with naloxone or buprenorphine alone during the first trimester.
Main Findings: The study found that prenatal exposure to buprenorphine with naloxone was associated with a lower risk of neonatal abstinence syndrome (37.4% vs 55.8%) and modest reductions in neonatal intensive care unit admission (30.6% vs 34.9%) and small for gestational age (10.0% vs 12.4%) compared to buprenorphine alone. No significant differences were observed for congenital malformations, low birth weight, preterm birth, respiratory symptoms, or cesarean delivery.
Implications for Practice: These findings suggest that buprenorphine combined with naloxone is a safe and potentially preferable option for treating opioid use disorder during pregnancy, providing more flexibility in treatment choices for pregnant individuals.
RCT: Methotrexate Shows Modest Pain Reduction in Knee Osteoarthritis, More Research Needed – Ann Intern Med
18 Aug, 2024 | 18:01h | UTCStudy Design and Population: This multicenter, randomized, double-blind, placebo-controlled trial evaluated the effects of oral methotrexate on 207 participants with symptomatic knee osteoarthritis (KOA) who had persistent knee pain despite prior treatments. Conducted across 15 musculoskeletal clinics in the UK from June 2014 to October 2017, participants were randomly assigned to receive either methotrexate or placebo over a 12-month period.
Main Findings: At 6 months, methotrexate resulted in a modest reduction in knee pain, with a statistically significant difference of 0.79 points on the NRS compared to placebo (95% CI, 0.08 to 1.51; P = 0.030). Small but statistically significant improvements were also noted in knee stiffness and function. However, the clinical significance of these findings remains uncertain, and potential side effects of methotrexate warrant caution.
Implications for Practice: While methotrexate may offer some symptomatic relief for patients with knee osteoarthritis who do not respond to standard treatments, the modest reduction in pain and improvement in function observed in this study may not justify its routine use given the potential for significant side effects. The small magnitude of benefit suggests that methotrexate should be considered cautiously and only in select patients. Further research is necessary to confirm these findings and to better understand the risk-benefit profile of methotrexate in this population before broader clinical adoption.
Systematic Review: Immune Checkpoint Inhibitors Plus Chemotherapy Improves Survival in NSCLC for Patients Aged 65-75 – Cochrane Database Syst Rev
18 Aug, 2024 | 15:24h | UTCStudy Design and Population: This Cochrane systematic review evaluated the efficacy and safety of immune checkpoint inhibitors (ICIs) combined with platinum-based chemotherapy versus platinum-based chemotherapy alone (with or without bevacizumab) in treatment-naïve older adults with advanced non-small cell lung cancer (NSCLC). The review included 17 randomized controlled trials (RCTs) with a total of 4,276 participants, focusing on three age groups: 65 years and older, 65-75 years, and 75 years and older.
Main Findings: The addition of ICIs to chemotherapy likely improves overall survival (HR 0.78, 95% CI 0.70 to 0.88) and progression-free survival (HR 0.61, 95% CI 0.54 to 0.68) in patients aged 65 years and older. For those aged 65-75, the benefits are more pronounced (HR 0.75 for overall survival; HR 0.64 for progression-free survival), although there may be an increase in treatment-related adverse events (RR 1.47). However, in patients over 75, the benefits in overall survival and progression-free survival are unclear, with a low-certainty evidence suggesting no significant improvement (HR 0.90 and HR 0.83, respectively).
Implications for Practice: The findings support the use of ICIs combined with chemotherapy in older adults aged 65-75 with advanced NSCLC, but caution is advised for those over 75 due to the lack of clear survival benefit and the potential for increased toxicity. Further research is needed to better understand the risks and benefits in the oldest patients.
Cohort Study: Long-Term Multivitamin Use Not Linked to Reduced Mortality in Over 390,000 US Adults
18 Aug, 2024 | 15:07h | UTCtudy Design and Population: This cohort study examined the association between daily multivitamin (MV) use and mortality risk using data from three large prospective cohorts in the United States. The study included 390,124 generally healthy adults with no prior history of cancer or major chronic diseases. Participants were followed for up to 27 years, with baseline MV use assessed between 1993 and 2001 and follow-up assessments from 1998 to 2004.
Main Findings: Daily MV use was not associated with a reduction in all-cause mortality. In fact, the study found a 4% higher risk of mortality among daily MV users compared to nonusers during the first half of the follow-up period (HR, 1.04; 95% CI, 1.02-1.07), although this risk was not significant in the second half. The findings were consistent across major causes of death, including heart disease, cancer, and cerebrovascular diseases.
Implications for Practice: These findings suggest that long-term MV use does not confer a mortality benefit among generally healthy adults. Healthcare providers may need to reconsider recommending MVs for longevity purposes, as the evidence does not support their efficacy in reducing mortality risk.
Updated Guidelines on Perioperative Management of Anticoagulant and Antiplatelet Therapy for Interventional Techniques – Pain Physician
18 Aug, 2024 | 14:52h | UTCIntroduction: The American Society of Interventional Pain Physicians (ASIPP) has published updated guidelines for the perioperative management of patients undergoing interventional techniques while receiving antiplatelet and anticoagulant therapy. These guidelines are essential for clinicians to balance the risk of thromboembolism against the risk of bleeding during interventional procedures.
Key Points:
1 – Risk of Thromboembolic Events:
– Thromboembolic events have a higher risk of morbidity and mortality compared to the risk of epidural hematoma. Thus, interruption of antithrombotic therapy should be carefully considered.
2 – Risk Stratification of Procedures:
– Interventional techniques are classified into three categories based on risk: low, moderate, or high. For high-risk procedures, cessation of anticoagulant or antiplatelet therapy is recommended, whereas for low to moderate-risk procedures, therapy may continue under certain conditions.
3 – Management of Direct Oral Anticoagulants (DOACs):
– DOACs such as dabigatran, apixaban, rivaroxaban, and edoxaban should generally be discontinued for 2 days before high-risk procedures and one day for moderate-risk procedures. Adjustments are needed based on renal function, specially for dabigatran.
4 – Discontinuation of Aspirin:
– For high-risk interventional procedures, discontinuation of aspirin (81 or 325 mg) is recommended 6 days before the procedure. However, for low to moderate-risk procedures, aspirin therapy may be continued or stopped for 3 days depending on individual risk factors and clinical judgment.
5 – Discontinuation of Other Antiplatelet Agents:
– Clopidogrel (Plavix) and Prasugrel (Effient): These agents should be discontinued 6 days before high-risk procedures. For low-risk procedures, these medications can be continued.
– Ticagrelor (Brilinta): Discontinue for 5 days before high-risk procedures, with consideration of patient-specific risk factors.
6 – Timing for Restarting Therapy:
– Antithrombotic therapy should typically be resumed within 12-24 hours after low to moderate-risk procedures and within 24-48 hours after high-risk procedures, depending on bleeding risk and patient status.
7 – Shared Decision-Making:
– Decisions on whether to continue or discontinue antithrombotic therapy should involve shared decision-making between the patient, the interventional pain specialist, and other treating physicians, considering all associated risks.
Conclusion: These guidelines provide a comprehensive framework for managing the delicate balance between thromboembolic and bleeding risks in patients on anticoagulant or antiplatelet therapy undergoing interventional procedures. They emphasize the importance of personalized care and multidisciplinary collaboration.
Innovative Antimicrobial Susceptibility Testing Bypasses Blood Culture, Promising Faster Sepsis Diagnosis – Nature
18 Aug, 2024 | 14:09h | UTCStudy Design and Population: This study introduces a novel ultra-rapid antimicrobial susceptibility testing (AST) method that bypasses the traditional blood culture process, potentially reducing diagnostic time by 40-60 hours. The method was evaluated using a cohort of 190 hospitalized patients in Korea with suspected sepsis, including those with blood cancers.
Main Findings: The new AST method identified bacterial species in all patients with positive blood infections, achieving a 100% match in species identification. For antimicrobial susceptibility, the method demonstrated a 94.9% categorical agreement with conventional AST methods, with a theoretical turnaround time of 13 ± 2.53 hours, significantly faster than current workflows.
Implications for Practice: This method could improve sepsis treatment by providing same-day results, potentially reducing sepsis-related mortality and the use of broad-spectrum antibiotics. However, further validation in a more diverse patient population is necessary to confirm its clinical efficacy and value.
RCT: Twice-Yearly Lenacapavir Prevents HIV Infections More Effectively Than Daily F/TAF in Women – N Engl J Med
18 Aug, 2024 | 13:56h | UTCStudy Design and Population: This phase 3, double-blind, randomized controlled trial included 5,338 adolescent girls and young women in South Africa and Uganda. Participants were assigned to receive either twice-yearly subcutaneous lenacapavir, daily oral emtricitabine–tenofovir alafenamide (F/TAF), or daily oral emtricitabine–tenofovir disoproxil fumarate (F/TDF) as an active control, with corresponding placebos.
Main Findings: Lenacapavir demonstrated superior efficacy in HIV prevention, with zero infections observed among its recipients. In contrast, the F/TAF group experienced 39 HIV infections (2.02 per 100 person-years), while the F/TDF group had 16 infections (1.69 per 100 person-years). HIV incidence was significantly lower with lenacapavir compared to background incidence and F/TDF, while no significant difference was observed between F/TAF and F/TDF.
Implications for Practice: Twice-yearly lenacapavir could be a more effective and potentially easier-to-adopt HIV prevention strategy than daily oral F/TAF in cisgender women, though considerations of injection-site reactions are necessary. This approach could improve adherence and outcomes in populations with low persistence in daily PrEP use.
CDC Updates Contraceptive Guidelines for 2024 – Centers for Disease Control and Prevention
18 Aug, 2024 | 13:51h | UTCIntroduction: The Centers for Disease Control and Prevention (CDC) has released updated recommendations in the “U.S. Selected Practice Recommendations for Contraceptive Use, 2024” and “U.S. Medical Eligibility Criteria for Contraceptive Use, 2024.” These guidelines provide healthcare providers with the latest evidence-based recommendations to support patient-centered contraceptive care, aiming to remove unnecessary barriers and ensure equitable access to contraception.
Key Points:
1 – Intrauterine Device (IUD) Placement:
– Routine use of misoprostol is not recommended for IUD placement, except in selected cases. Lidocaine (topical or paracervical block) is newly recommended to reduce patient pain during IUD placement.
2 – Bleeding Irregularities with Implants:
– Hormonal treatments and antifibrinolytic agents may improve bleeding irregularities associated with implant use, although bleeding often recurs after stopping treatment. NSAIDs and selective estrogen-receptor modulators may also be effective, with benefits persisting post-treatment.
3 – Testosterone Use and Pregnancy Risk:
– Testosterone therapy may not prevent pregnancy in transgender, gender-diverse, and nonbinary individuals with a uterus. Contraceptive counseling and services should be offered to those at risk of pregnancy who do not desire it.
4 – Self-Administration of Injectable Contraceptives:
– Subcutaneous depot medroxyprogesterone acetate (DMPA-SC) should be available for self-administration, providing an additional option for those seeking injectable contraception.
5 – Updates in Medical Eligibility Criteria:
– The 2024 guidelines include revised recommendations for patients with chronic kidney disease, updates for those who are breastfeeding, postpartum, or post-abortion, and considerations for individuals with obesity, cardiovascular conditions, and other comorbidities.
6 – Patient-Centered Counseling:
– The guidelines emphasize the importance of providing contraceptive care in a noncoercive manner, supporting the individual’s values, goals, and reproductive autonomy. Healthcare providers are encouraged to recognize and address structural inequities and avoid discrimination in contraceptive counseling.
Conclusion: These updated guidelines from the CDC are designed to support healthcare providers in delivering equitable, patient-centered contraceptive care. By removing unnecessary barriers and providing clear guidance on managing complex contraceptive issues, the recommendations aim to improve access to contraception and support informed, autonomous decision-making among patients.
Guideline Reference: Curtis, K. M., Nguyen, A. T., Tepper, N. K., et al. (2024). U.S. Selected Practice Recommendations for Contraceptive Use, 2024. MMWR Recommendations and Reports, 73(3).