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Cohort Study: Impact of decreasing eGFR on serious adverse drug reactions in CKD patients – Am J Kidney Dis
25 May, 2024 | 18:48h | UTCThis prospective cohort study, part of the French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN), involved 3,033 outpatients with moderate to advanced chronic kidney disease (CKD). The study aimed to explore the correlation between estimated glomerular filtration rate (eGFR) and the incidence of serious adverse drug reactions (ADRs). Over a median follow-up of 4.7 years, 360 patients experienced 488 serious ADRs, predominantly kidney and urinary disorders, and hemorrhages, constituting 70% of cases. The study identified antithrombotics and renin-angiotensin system inhibitors as the most common medication classes leading to these ADRs. A significant finding was that a decrease in eGFR is associated with a higher risk of serious ADRs, specifically acute kidney injury and bleeding, which were largely preventable or potentially preventable. The outcomes highlight the critical need for careful drug prescription and monitoring in CKD patients to mitigate serious ADRs.
Reference (link to free full-text):
New ACC/AHA Guidelines for the Management of Lower Extremity Peripheral Artery Disease
16 May, 2024 | 11:05h | UTCIntroduction
The 2024 ACC/AHA guidelines, along with several associated societies, highlight the significance of peripheral artery disease (PAD) as a major public health issue, often underestimated, and linked to high risks of amputation and serious cardiovascular events. This document is crucial for clinicians seeking to optimize treatment and improve the quality of life for affected patients.
Key Points
1 – Risk Assessment: It is crucial to evaluate risks associated with PAD and health disparities that may impact treatment outcomes.
2 – Diagnosis: Diagnosis of PAD typically involves physical examination, medical history, and the resting ankle-brachial index.
3 – Medical Therapy: Management includes antiplatelet therapy (usually single), high-intensity statins, antihypertensive therapy, diabetes management, and smoking cessation. Rivaroxaban (2.5 mg twice daily) combined with low-dose aspirin (81 mg) has proven effective and can be included in the therapy for patients at low risk of bleeding.
4 – Structured Exercise: A central component of care, including supervised exercise therapy and community-based programs.
5 – Revascularization: Indicated to prevent limb loss in chronic limb-threatening ischemia and can improve quality of life in cases of claudication.
6 – Multidisciplinary Care: Optimized care involves a team of multiple specialties, especially for chronic limb-threatening ischemia.
New Guidelines for the Management of Corticosteroid-Induced Adrenal Insufficiency – J Clin Endocrinol Metab
15 May, 2024 | 11:21h | UTCIntroduction:
The European Society of Endocrinology and the Endocrine Society have co-published the first joint clinical guideline, focusing on the diagnosis and therapy for glucocorticoid-induced adrenal insufficiency. This document serves as an essential tool for health professionals involved in the care of patients undergoing chronic glucocorticoid therapy.
Key Points:
- Patient Education: Clinicians are recommended to inform patients about the endocrine effects of glucocorticoid treatment, particularly in relation to adrenal insufficiency.
- No Tapering in Short-Term Therapies: It is suggested not to taper glucocorticoid therapies of short duration (<3-4 weeks), regardless of the dose.
- Careful Tapering: For long-term therapies, tapering should be done gradually, especially when approaching physiological daily equivalent doses (e.g., 4-6 mg of prednisone).
- Monitoring Withdrawal Syndrome: Consideration of glucocorticoid withdrawal syndrome that may occur during tapering, adjusting the dose as needed to alleviate symptoms.
- Testing for Adrenal Insufficiency: Morning serum cortisol is recommended as the first test in the suspicion of disorders in the recovery of the HPA axis after cessation of glucocorticoids.
These guidelines offer practical and evidence-based guidance for managing patients who develop adrenal insufficiency due to prolonged use of glucocorticoids, emphasizing the importance of patient education and careful monitoring during the tapering process.
Reference (link to free full-text):
FDA grants approval for Colosense, a noninvasive stool RNA-based test for colorectal cancer screening
11 May, 2024 | 17:48h | UTCGeneoscopy, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved ColoSense™, a noninvasive stool RNA-based test for colorectal cancer (CRC) screening in adults aged 45 and older who are at average risk for CRC.
Test Performance and Specifications:
– Sensitivity and Specificity: In the CRC-PREVENT trial, ColoSense demonstrated a sensitivity of 93% for detecting colorectal cancer and 45% sensitivity for detecting advanced adenomas (AA).
– Technology: ColoSense employs a multi-target stool RNA (mt-sRNA) approach, detecting colorectal neoplasia-associated RNA markers and occult hemoglobin. This method is designed to overcome variability in test performance that can occur with age-related changes in other biomarkers.
– Breakthrough Device Designation: The test has been designated as a Breakthrough Device by the FDA, acknowledging its potential to offer more effective diagnosis compared to existing methods.
– Accessibility: ColoSense is intended to facilitate increased screening uptake by providing a noninvasive alternative to traditional colonoscopy, particularly among populations reticent about invasive procedures.
Clinical Application:
– Screening Recommendations: Approved for individuals at typical average risk for CRC, ColoSense aligns with updated screening guidelines that recommend starting CRC screening at age 45.
– Role in Screening Strategy: ColoSense is indicated for use as a screening tool but is not intended to replace diagnostic or surveillance colonoscopy in individuals at high risk for CRC.
Geneoscopy is working towards a commercial launch of ColoSense in collaboration with Labcorp (NYSE: LH), aiming to make the test available by late 2024 or early 2025. (link to news release)
2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy – J Am Coll Cardiol
11 May, 2024 | 14:20h | UTCIn a significant advancement for the treatment of hypertrophic cardiomyopathy (HCM), the American Heart Association and the American College of Cardiology, along with other leading societies, have released updated guidelines to optimize patient care. Here are the essential updates and recommendations for practicing physicians:
1 – Updated Diagnostic Strategies: The guideline emphasizes the use of advanced imaging techniques and genetic testing to enhance diagnostic accuracy, enabling personalized treatment approaches.
2 – Risk Assessment Tools: Revised tools for sudden cardiac death (SCD) risk assessment are detailed, aiding clinicians in making informed decisions regarding the use of implantable cardioverter-defibrillators (ICDs).
3 – Management of Obstructive HCM: New recommendations for the pharmacological treatment of symptomatic obstructive HCM include the use of disopyramide and advanced therapies such as septal reduction when initial medication does not suffice.
4 – Guidelines on Exercise and Lifestyle: The guidelines provide a nuanced approach to physical activity, recognizing the benefits while outlining the risks for patients with HCM. Detailed advice is offered on managing competitive sports involvement and other lifestyle considerations.
5 – Multidisciplinary Approach: The guidelines advocate for a team-based approach involving specialized HCM centers, ensuring patients benefit from comprehensive expertise and the latest treatment modalities.
6 – Innovations in Treatment: Highlighting new therapeutic options like myosin inhibitors, the guidelines underscore their role in managing obstructive symptoms when traditional medications are inadequate.
7 – Special Populations: Detailed sections on the management of HCM in children and pregnant women, addressing the unique challenges these groups face.
These guidelines represent a cornerstone in the evolving landscape of HCM management, embodying a commitment to enhancing outcomes and quality of life for patients through evidence-based practices and collaborative care.
Reference (link to free full-text):
RCT: Triple combination of paracetamol, ibuprofen, and dexamethasone reduces morphine use post-hip arthroplasty – Lancet Rheumatol
11 May, 2024 | 14:18h | UTCStudy Design and Population: The RECIPE trial was a randomized, blinded, placebo-controlled multicenter study conducted across nine Danish hospitals to evaluate the effectiveness of non-opioid analgesic combinations in managing postoperative pain following total hip arthroplasty. A total of 1,060 adults scheduled for surgery were enrolled and randomly assigned to one of four treatment groups, receiving combinations of paracetamol, ibuprofen, and dexamethasone. The study’s primary endpoint was the 24-hour intravenous morphine consumption, with a predefined minimal important difference set at 8 mg.
Main Findings: The trial results indicated significant reductions in 24-hour morphine consumption in the group receiving paracetamol, ibuprofen, and dexamethasone combined, compared to other groups, though none reached the minimal important difference. Specifically, this group consumed a median of 15 mg morphine, which was less than the other groups ranging from 16 mg to 24 mg. However, the differences did not meet the study’s threshold for a clinically important effect. Adverse events were lowest in the combined treatment group, suggesting a better safety profile primarily characterized by fewer incidents of nausea, vomiting, and dizziness.
Implications for Practice: The findings support the use of a combined regimen of paracetamol, ibuprofen, and dexamethasone for reducing morphine consumption post-total hip arthroplasty, which could be significant in clinical settings aiming to minimize opioid use. The improved safety profile also highlights the potential benefits of multimodal analgesia. Further research may explore the optimization of dosing schedules and long-term outcomes to enhance patient recovery and satisfaction.
Reference (link to abstract – $ for full-text):
Cohort Study: Late ventricular arrhythmias are rare in STEMI patients without left ventricular dysfunction post-primary PCI – JAMA Netw Open
11 May, 2024 | 14:15h | UTCStudy Design and Population: This cohort study analyzed data from the US National Cardiovascular Data Registry Chest Pain–MI Registry, involving 174,126 adults with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) from 2015 to 2018. The population included a broad demographic with a focus on those experiencing late ventricular tachycardia (VT) or ventricular fibrillation (VF) post-PCI, specifically examining occurrences one day or more after the intervention.
Main Findings: The study found that 8.9% of the patients developed VT or VF after PCI, with 2.4% experiencing these arrhythmias late in the hospitalization period. Among patients with uncomplicated STEMI, late VT or VF with cardiac arrest was exceedingly rare, occurring in only 0.1%. Notably, reduced left ventricular ejection fraction was strongly associated with an increased risk of late VT or VF with cardiac arrest. The presence of late VT or VF significantly correlated with higher in-hospital mortality rates.
Implications for Practice: The findings suggest that late VT or VF after primary PCI in STEMI patients is infrequent, particularly among those without complications. This data supports the potential for safe earlier hospital discharge in uncomplicated cases. However, vigilance is advised due to the significant mortality risk associated with late VT or VF events. Clinicians should consider patient-specific risk factors such as left ventricular function when making discharge decisions.
Reference (link to free full-text):
RCT: KarXT (xanomeline–trospium) demonstrates significant symptom reduction in schizophrenia compared to placebo – The Lancet
11 May, 2024 | 13:42h | UTCStudy Design and Population: The EMERGENT-2 study was a randomized, double-blind, placebo-controlled, flexible-dose, 5-week phase 3 trial conducted across 22 inpatient sites in the USA. It targeted adults aged 18–65 years diagnosed with schizophrenia, exhibiting a recent exacerbation in psychotic symptoms. A total of 252 participants, each with a Positive and Negative Syndrome Scale (PANSS) score of 80 or higher and a Clinical Global Impression-Severity score of 4 or more, were enrolled and randomized equally into two groups to receive either the muscarinic receptor agonist KarXT (xanomeline–trospium) or a placebo.
Main Findings: KarXT significantly reduced the PANSS total scores from baseline to week 5, with a mean decrease of 21.2 points compared to 11.6 points in the placebo group (least squares mean difference -9.6; 95% CI -13.9 to -5.2; p<0.0001; Cohen’s d=0.61). All secondary endpoints were also met favorably for KarXT. Common adverse events for KarXT included constipation, dyspepsia, and nausea, but rates of extrapyramidal symptoms were similar between the two groups. The treatment was generally well tolerated with comparable discontinuation rates due to adverse events.
Implications for Practice: These results indicate that KarXT could represent a new class of antipsychotic treatment, diverging from traditional D2 dopamine receptor antagonists and instead leveraging muscarinic receptor activation. The promising outcomes observed in EMERGENT-2 suggest that KarXT has the potential to improve both positive and negative symptoms of schizophrenia while maintaining a favorable safety profile. Ongoing and future studies (EMERGENT-3, EMERGENT-4, and EMERGENT-5) will further elucidate the long-term efficacy and safety of KarXT.
Reference (link to abstract – $ for full-text):
Meta-analysis reveals 24% prevalence of eating disorders among individuals with insulin-dependent diabetes – Eat Behav
11 May, 2024 | 13:41h | UTCThis systematic review and meta-analysis evaluated the prevalence of eating disorder symptoms (EDS) in individuals aged 16 and older with insulin-dependent diabetes, covering both type 1 and type 2 diabetes. The study involved an extensive search across several databases including PubMed, Embase, Scopus, PsycINFO, and CINAHL, culminating in the inclusion of 45 studies. The meta-analysis revealed a pooled prevalence of EDS at 24% (95% CI 0.21–0.28), with prevalence reaching 27% (95% CI 0.24–0.31) among studies using the Diabetes Eating Problem Survey-Revised (DEPS-R), the most frequently utilized screening tool. Notably, the prevalence of EDS varied based on the screening tool used and was significantly associated with sex distribution; studies with a higher percentage of female participants (over 58%) reported a higher prevalence of EDS (30% vs. 18%, prevalence ratio 1.7). The study also highlighted a concerning prevalence of insulin omission, reported at 21% (95% CI 0.13–0.33). This analysis underscores the substantial occurrence of eating disorder symptoms among this patient population, emphasizing the need for tailored screening and interventions.
Reference (link to abstract – $ for full-text):
Cluster Randomized Trial: Hyperangulated video laryngoscopy reduces intubation attempts in surgical patients – JAMA
11 May, 2024 | 13:39h | UTCStudy Design and Population: This cluster randomized multiple crossover clinical trial was conducted at a single U.S. academic hospital to compare the effectiveness of hyperangulated video laryngoscopy versus direct laryngoscopy in reducing the number of intubation attempts during surgery. The study involved 7,736 adult patients, aged 18 years or older, undergoing elective or emergent cardiac, thoracic, or vascular surgical procedures that required single-lumen endotracheal intubation for general anesthesia. The trial randomized two sets of 11 operating rooms on a weekly basis to use either video laryngoscopy or direct laryngoscopy for the initial intubation attempt from March 2021 to December 2022.
Main Findings: Hyperangulated video laryngoscopy significantly decreased the number of intubation attempts compared to direct laryngoscopy. Specifically, 1.7% of surgical procedures using video laryngoscopy required more than one intubation attempt versus 7.6% for direct laryngoscopy, with an estimated proportional odds ratio of 0.20 (95% CI, 0.14-0.28; P < .001). Furthermore, intubation failure was markedly lower with video laryngoscopy (0.27%) compared to direct laryngoscopy (4.0%). However, there was no significant difference in the rates of airway and dental injuries between the two methods.
Implications for Practice: The findings indicate that hyperangulated video laryngoscopy enhances initial intubation success and reduces the need for multiple intubation attempts in a variety of surgical settings. This suggests that video laryngoscopy could be considered a preferable technique for endotracheal intubation in the operating room, potentially improving patient outcomes and efficiency. Further research might explore the generalizability of these results to other medical centers and different patient populations.
Reference (link to abstract – $ for full-text):
RCT: Video laryngoscopy improves first-attempt intubation success in neonates compared to direct laryngoscopy – N Engl J Med
11 May, 2024 | 13:37h | UTCStudy Design and Population: This single-center randomized clinical trial investigated the efficacy of video laryngoscopy versus direct laryngoscopy for urgent intubation in neonates. A total of 226 neonates requiring intubation either in the delivery room or neonatal intensive care unit (NICU) were enrolled and stratified by gestational age into two groups: less than 32 weeks and 32 weeks or more. The study primarily focused on the success rate of the first intubation attempt, monitored through exhaled carbon dioxide detection.
Main Findings: The trial included 214 neonates, analyzing the success of intubation on the first attempt. Video laryngoscopy significantly outperformed direct laryngoscopy, achieving a first-attempt success rate of 74% (95% confidence interval [CI], 66 to 82) compared to 45% (95% CI, 35 to 54) in the direct laryngoscopy group. Moreover, the median number of attempts for successful intubation was lower in the video-laryngoscopy group (1 attempt, 95% CI, 1 to 1) versus the direct-laryngoscopy group (2 attempts, 95% CI, 1 to 2). Additionally, neonates in the video laryngoscopy group experienced higher median lowest oxygen saturations and heart rates during intubation.
Implications for Practice: The findings suggest that video laryngoscopy could be more effective than direct laryngoscopy for urgent neonatal intubation, particularly in increasing the likelihood of success on the first attempt. These results recommend reconsidering current intubation techniques in neonatal care settings to incorporate video laryngoscopy, potentially leading to safer and more efficient intubation processes in this vulnerable population.
Reference (link to abstract – $ for full-text):
RCT: Cytisinicline shows promising results in enhancing vaping cessation among adults – JAMA Intern Med
11 May, 2024 | 13:35h | UTCStudy Design and Population: The ORCA-V1 study was a double-blind, placebo-controlled randomized clinical trial conducted across five US clinical sites from July 2022 to February 2023. It enrolled 160 adults who used nicotine e-cigarettes daily and expressed a desire to quit, but were not current cigarette smokers. Participants were predominantly middle-aged (mean age 33.6 years), with a slight female majority (51.9%).
Main Findings: The trial assessed cytisinicline, a plant-based alkaloid, compared to placebo over a 12-week period with follow-up to 16 weeks. Results showed that cytisinicline significantly increased continuous abstinence from e-cigarette use during the last four weeks of treatment (31.8% vs 15.1% with placebo; odds ratio, 2.64; 95% CI, 1.06-7.10; P = .04). The effect was less pronounced but still present during the four weeks post-treatment (23.4% vs 13.2% with placebo; odds ratio, 2.00; 95% CI, 0.82-5.32; P = .15). The medication was well-tolerated, with only 3.8% of the cytisinicline group discontinuing due to adverse events.
Implications for Practice: Cytisinicline offers a promising pharmacotherapy option for adults seeking to quit vaping, demonstrating both efficacy and safety in this trial. Further research in larger populations and over longer periods is needed to confirm these findings and fully establish cytisinicline’s role in treating nicotine e-cigarette dependence.
Reference (link to abstract – $ for full-text):
Phase 2 RCT: Preventive subcutaneous L9LS monoclonal antibody reduces malaria incidence by 66-70% in Malian children – N Engl J Med
7 May, 2024 | 15:31h | UTCThis phase 2 randomized clinical trial investigated the safety and efficacy of the monoclonal antibody L9LS in preventing Plasmodium falciparum infection and clinical malaria in children aged 6 to 10 years in Mali. The trial was structured in two parts: initial dose assessment in adults followed by a randomized, placebo-controlled test in children over a 6-month malaria season. A total of 225 children participated, divided equally among three groups to receive either 150 mg of L9LS, 300 mg of L9LS, or a placebo. Results demonstrated a significant reduction in the rate of P. falciparum infection—66% efficacy with the 150-mg dose and 70% efficacy with the 300-mg dose. Similarly, efficacy against clinical malaria was 67% with the 150-mg dose and 77% with the 300-mg dose. Both doses were well-tolerated with no safety concerns reported, underscoring the potential of L9LS as a preventative treatment against malaria in endemic regions.
Reference (link to abstract – $ for full-text):
Meta-Analysis: Acute adverse effects of therapeutic psilocybin doses in treating depression and anxiety – JAMA Netw Open
7 May, 2024 | 15:29h | UTCThis meta-analysis examined the acute adverse effects of psilocybin when used in therapeutic doses for treating depression and anxiety. The study analyzed data from six randomized, double-blind clinical trials involving a total of 528 participants. Significant adverse effects identified included headaches, nausea, anxiety, dizziness, and elevated blood pressure, compared to controls. No significant risks of paranoia or transient thought disorder were associated with psilocybin use. Overall, the adverse effects were tolerable and typically resolved within 48 hours, although the study calls for further research into their management.
Reference (link to free full-text):
RCT: Effects of combined time-restricted eating and high-intensity functional training on body composition and cardiometabolic health in women with obesity – PLOS One
7 May, 2024 | 15:28h | UTCThis randomized clinical trial investigated the effects of time-restricted eating (TRE) and high-intensity functional training (HIFT), both separately and in combination, on body composition and cardiometabolic health in inactive women with obesity. Sixty-four participants were assigned to three groups: TRE alone, HIFT alone, and both TRE and HIFT (TRE-HIFT). Over 12 weeks, the TRE-HIFT group showed the most significant improvements in waist and hip circumference, fat mass, total cholesterol, triglyceride levels, insulin sensitivity, and blood glucose levels compared to the other groups. Weight and BMI reductions were also more substantial in the TRE-HIFT group than in the HIFT-only group. Furthermore, while all groups exhibited improvements, those combining both interventions experienced more pronounced changes in cardiometabolic parameters, suggesting the potential of integrated lifestyle interventions for enhancing health outcomes in this population.
Reference (link to free full-text):
RCT: Oral and topical minoxidil equally effective for male hair loss treatment – JAMA Dermatol
7 May, 2024 | 15:26h | UTCThis study examines the effectiveness, safety, and tolerability of oral minoxidil compared to topical minoxidil in treating male androgenetic alopecia. Conducted as a double-blind, placebo-controlled randomized clinical trial, 90 men aged 18 to 55 with varying degrees of hair loss were recruited and followed for 24 weeks. Participants were divided into two groups: one receiving oral minoxidil 5 mg daily and the other using topical minoxidil 5% twice daily. The primary endpoint was the change in terminal hair density in both the frontal and vertex regions. Results showed that oral minoxidil did not outperform topical minoxidil in terms of increasing hair density on the frontal scalp, though it did show a slight superiority on the vertex area. Common side effects for the oral minoxidil group included hypertrichosis and headaches. Overall, oral minoxidil demonstrated similar efficacy to its topical counterpart and offers an alternative for patients preferring oral treatment or those intolerant to topical formulations.
Reference (link to abstract – $ for full-text):
Review: Acute and complicated inflammatory pericarditis – Mayo Clin Proc
6 May, 2024 | 18:03h | UTCThe article provides a comprehensive review of current approaches to the diagnosis and management of inflammatory pericardial disease, with a particular focus on acute and complicated cases of pericarditis. Here’s a summary tailored for a medical audience:
Key Points:
1 – Epidemiology and Presentation:
– Acute pericarditis is relatively common, particularly among younger populations.
– It can be effectively managed in most cases but poses a significant risk of recurrence and morbidity if not properly treated.
– Presentations can vary, with chest pain being a predominant symptom, which improves upon leaning forward and worsens in the supine position.
2 – Diagnostic Evaluation:
– Diagnosis hinges on a combination of clinical signs (e.g., chest pain, pericardial rub), ECG changes, imaging findings, and laboratory markers (elevated CRP and white blood cell count).
– Multimodality imaging plays a critical role in diagnosis and management, including echocardiography, CT, and MRI to evaluate pericardial effusion and inflammation.
3 – Management Strategies:
– The treatment landscape has evolved with the introduction of targeted anti-inflammatory therapies and a more systematic approach to care.
– Management includes NSAIDs as first-line therapy, colchicine to reduce recurrence rates, and corticosteroids for severe cases. Recent advancements include the use of interleukin-1 receptor blockers for complicated cases.
– Pericardiectomy may be considered in chronic or recurrent cases that are refractory to medical management.
4 – Future Directions:
– Ongoing research is directed at improving diagnostic accuracy through advanced imaging techniques and refining treatment protocols to minimize recurrence and manage complicated cases effectively.
– The integration of novel biological agents and personalized medicine approaches is anticipated to enhance outcomes for patients with pericardial disease.
This article emphasizes the importance of a protocol-driven approach to the initial care, the use of targeted therapeutics based on individual patient profiles, and the integration of care pathways to manage acute and complicated pericarditis effectively.
Reference (link to free full-text):
Malik, A. A., Lloyd, J. W., Anavekar, N. S., & Luis, S. A. (2024). Acute and Complicated Inflammatory Pericarditis: A Guide to Contemporary Practice. Mayo Clinic Proceedings, 99(5), 795-811. https://doi.org/10.1016/j.mayocp.2024.01.012
RCT: No significant benefit of adjuvant prednisone for patients with cystic fibrosis with exacerbations unresponsive to antibiotics – Eur Respir J
6 May, 2024 | 06:32h | UTCThis randomized, double-blind, placebo-controlled trial investigated the effectiveness of adjuvant oral prednisone in enhancing lung function recovery in patients with cystic fibrosis (CF) experiencing pulmonary exacerbations (PExs) unresponsive to initial intravenous (IV) antibiotic treatment. The study involved 173 participants, with 76 not achieving more than 90% of their baseline forced expiratory volume in one second (ppFEV1) by Day 7 of antibiotic treatment and subsequently randomized to receive either oral prednisone (1 mg·kg−1 twice daily, up to 60 mg/day) or placebo for an additional 7 days. Results showed that 50% of the prednisone group and 39% of the placebo group recovered over 90% of their baseline ppFEV1 by Day 14. However, the difference was not statistically significant (11% difference; 95% CI -11, 34%; p=0.34). Additionally, prednisone did not significantly prolong the time to the next exacerbation compared to placebo. This study concludes that adjuvant oral prednisone does not significantly improve lung function recovery or delay subsequent exacerbations in CF patients not responding to initial antibiotic therapy.
Reference (link to abstract – $ for full-text):
RCT: Azithromycin fails to prevent moderate or severe chronic lung disease in preterm infants – Lancet Respir Med
6 May, 2024 | 06:28h | UTCThis randomized, placebo-controlled trial evaluated the effectiveness of azithromycin in preventing chronic lung disease (CLD) in preterm infants born at less than 30 weeks’ gestation across 28 UK neonatal intensive care units. A total of 799 infants were randomized to receive either intravenous azithromycin or a placebo. The primary outcome measured was survival without moderate or severe CLD at 36 weeks postmenstrual age. Results showed no significant difference between the azithromycin group (42% survival without CLD) and the placebo group (45% survival without CLD), with an adjusted odds ratio of 0.84 (95% CI 0.55–1.29, p=0.43). Pulmonary Ureaplasma spp colonization did not affect the treatment outcome. Given the lack of efficacy and the presence of several serious adverse events in the azithromycin group, the study concluded that azithromycin should not be recommended for preventing CLD in this population.
Reference (link to free full-text):
Cohort Study: Extending colonoscopy intervals to 15 years seems feasible in after a negative initial test in individuals without family history of CRC – JAMA Oncol
6 May, 2024 | 06:25h | UTCThis cohort study analyzed Swedish register-based data, examining colorectal cancer (CRC) diagnoses and CRC-specific mortality. The study included 110,074 individuals with a negative first colonoscopy (exposed group) and 1,981,332 matched controls, from 1990 to 2018. Participants were aged 45 to 69 at initial screening and were followed for up to 29 years.
During the follow-up, 484 new CRC cases and 112 CRC-specific deaths occurred in the exposed group. The study found significantly lower risks of CRC and CRC-specific death in the exposed group compared to controls over 15 years. The data suggest extending the screening interval from 10 to 15 years could miss only 2 CRC cases and prevent 1 CRC-specific death per 1,000 individuals while potentially reducing unnecessary colonoscopies.
The findings suggest that for individuals with no family history of CRC and a negative initial screening, the standard 10-year colonoscopy interval could safely be extended to 15 years. This adjustment could decrease the number of invasive procedures without significantly impacting cancer incidence and mortality, optimizing resource allocation and reducing patient burden.
Reference (link to abstract – $ for full-text):
Randomized Crossover Trial: Prophylactic recombinant ADAMTS13 prevents acute events in congenital thrombotic thrombocytopenic purpura – N Engl J Med
6 May, 2024 | 06:22h | UTCThis study evaluates the efficacy and safety of recombinant ADAMTS13 compared to standard plasma-derived therapy in managing congenital thrombotic thrombocytopenic purpura (TTP). In a phase 3, open-label, crossover trial involving 48 patients, each participant underwent two 6-month prophylaxis periods, receiving either recombinant ADAMTS13 or standard therapy, followed by a switch to the alternate treatment. Results indicate that recombinant ADAMTS13 prevented acute TTP events during prophylaxis, with no events recorded, versus one event under standard therapy. Furthermore, recombinant ADAMTS13 was associated with significantly lower rates of thrombocytopenia and adverse events compared to standard therapy. The treatment increased ADAMTS13 activity to approximately 100% of normal levels, with no development of neutralizing antibodies. Overall, recombinant ADAMTS13 was found to be safe and more effective than standard therapy in preventing TTP events and manifestations.
Reference (link to abstract – $ for full-text):
SCCM/IDSA Updated guidelines for evaluating new fever in adult ICU patients – Crit Care Med
5 May, 2024 | 15:12h | UTCThe 2023 revision of the guidelines for assessing new-onset fever in adult ICU patients stresses rigorous diagnostic processes using the GRADE methodology. These guidelines, developed without industry funding, offer 12 recommendations and nine best-practice statements focused primarily on the accurate measurement of core body temperature and initial diagnostic evaluations geared towards identifying potential infectious causes. Central temperature monitoring is recommended when possible; otherwise, oral or rectal measurements are preferred. The utility of imaging studies and rapid diagnostic tests is highlighted, along with the selective use of biomarkers to guide the cessation of antimicrobial therapy. The guidelines underscore that most recommendations are based on weak evidence, thus highlighting the need for continued research in diagnostic methodologies and fever management in the ICU setting.
Reference (link to free full-text):
M-A: Effects of long-term salt substitution on cardiovascular mortality and events – Ann Intern Med
5 May, 2024 | 15:10h | UTCThis systematic review and meta-analysis assessed the impact of long-term salt substitution on cardiovascular outcomes by analyzing data from 16 randomized controlled trials (RCTs). The primary investigation focused on mortality, major cardiovascular events (MACE), and adverse events with a study period of six months or longer. Key findings include a potential reduction in all-cause mortality (rate ratio [RR] of 0.88) and cardiovascular mortality (RR of 0.83), based on low-certainty evidence from studies predominantly conducted in China or Taiwan among older adults or those at higher cardiovascular risk. Results also indicated a slight reduction in MACE (RR of 0.85) with very low certainty. Evidence suggests no significant increase in serious adverse events. Limitations include the dominance of a single large RCT and limited generalizability of results to Western populations. The study concludes that while salt substitution could reduce mortality, the effects on cardiovascular events remain uncertain, with more robust evidence needed for broader demographic applicability.
Reference (link to abstract – $ for full-text):
Prospective Validation Study: High accuracy of PECARN rules in reducing unnecessary CT scans in pediatric blunt trauma – Lancet Child Adolesc Health
5 May, 2024 | 15:08h | UTCStudy Design and Population:
This multicenter prospective validation study tested the Pediatric Emergency Care Applied Research Network (PECARN) prediction rules aimed at reducing unnecessary CT scans for children presenting with blunt abdominal or minor head trauma. Over a nearly five-year period, children and adolescents under 18 from six U.S. emergency departments in cities including Sacramento, Dallas, and Los Angeles were enrolled. Exclusion criteria included pregnancy, pre-existing neurological disorders, penetrating trauma, injuries older than 24 hours, prior CT or MRI scans, or suspicion of non-accidental trauma.
Main Findings:
A total of 7,542 children with blunt abdominal trauma and 19,999 with minor head trauma were enrolled. The intra-abdominal injury rule demonstrated a sensitivity and negative predictive value (NPV) of 100%, confirming its reliability in detecting injuries requiring acute intervention. For head traumas, the sensitivity varied slightly with age; 100% for children under 2 years and 98.8% for those aged 2 years and older, with an NPV of 100% in both groups. Only two cases in the older cohort were misclassified, neither requiring neurosurgery.
Implications for Practice:
The validation of PECARN rules with high sensitivity and NPV supports their use as a safe guideline to minimize unnecessary CT scans in pediatric trauma cases, thereby promoting efficient use of resources and reducing exposure to radiation in children. These results suggest that implementation of these rules should be considered in emergency pediatric care to improve outcomes and healthcare efficiency.
Reference (link to abstract – $ for full-text):
RCT: Adding Ibrutinib to immunochemotherapy and autologous stem-cell transplantation improves PFS in young mantle cell lymphoma patients but increases toxicity – The Lancet
5 May, 2024 | 15:02h | UTCStudy Design and Population:
This study is a three-arm, randomized, open-label, phase 3 superiority trial named TRIANGLE, conducted across 165 centers in Europe and Israel. It aimed to compare the effectiveness of adding ibrutinib to standard immunochemotherapy, both with and without autologous stem-cell transplantation (ASCT), in 870 previously untreated mantle cell lymphoma patients aged 18-65 years, suitable for ASCT.
Main Findings:
After a median follow-up of 31 months, the arm with ibrutinib added to immunochemotherapy followed by ASCT (group A+I) demonstrated a 3-year failure-free survival rate of 88% compared to 72% in the standard immunochemotherapy plus ASCT group (group A). This indicates a significant improvement (hazard ratio 0.52; p=0.0008). Conversely, the efficacy of ASCT in the presence of ibrutinib (group A+I vs. group I, ibrutinib without ASCT) remains under analysis. Adverse events were more frequent and severe post-ASCT, particularly concerning hematological complications and infections.
Implications for Practice:
The results suggest that adding ibrutinib to first-line immunochemotherapy regimens significantly enhances clinical outcomes in younger patients with mantle cell lymphoma. However, the increased toxicity observed warrants careful patient monitoring, especially following ASCT. Further research is needed to evaluate the necessity and timing of ASCT in regimens containing ibrutinib.
Reference (link to free full-text):