Randomized Trials
RCT: Intravenous Amino Acids Reduce AKI Incidence in Cardiac Surgery Patients – N Engl J Med
3 Aug, 2024 | 19:12h | UTCStudy Design and Population: In this multinational, double-blind, randomized clinical trial, 3511 adult patients scheduled for cardiac surgery with cardiopulmonary bypass were recruited from 22 centers across three countries. Patients were randomly assigned to receive an intravenous infusion of either a balanced mixture of amino acids (2 g/kg/day) or a placebo (Ringer’s solution) for up to three days.
Main Findings: The primary outcome, occurrence of acute kidney injury (AKI), was significantly lower in the amino acid group (26.9%) compared to the placebo group (31.7%) with a relative risk of 0.85 (95% CI, 0.77 to 0.94; P=0.002). The incidence of severe AKI (stage 3) was also reduced in the amino acid group (1.6% vs. 3.0%; relative risk, 0.56; 95% CI, 0.35 to 0.87). There were no substantial differences between the groups regarding secondary outcomes such as the use and duration of kidney-replacement therapy or all-cause 30-day mortality.
Implications for Practice: The infusion of amino acids in adult patients undergoing cardiac surgery appears to reduce the incidence of AKI, indicating a potential protective renal effect. However, this intervention did not significantly impact other secondary outcomes, including mortality and the use of kidney-replacement therapy. These findings suggest that amino acids could be considered as a strategy to mitigate AKI risk in this patient population, although further research is needed to explore long-term benefits and other clinical outcomes.
RCT: Liberal vs. Restrictive Transfusion Strategy Shows No Significant Difference in Neurologic Outcomes for Traumatic Brain Injury Patients – N Engl J Med
3 Aug, 2024 | 19:06h | UTCStudy Design and Population: This randomized clinical trial evaluated the effects of liberal versus restrictive red cell transfusion strategies in 742 adults with moderate to severe traumatic brain injury (TBI) and anemia. Participants were randomized to either a liberal transfusion strategy (initiated at hemoglobin ≤10 g/dL) or a restrictive strategy (initiated at hemoglobin ≤7 g/dL). The primary outcome was an unfavorable neurologic outcome at 6 months, assessed using the Glasgow Outcome Scale–Extended.
Main Findings: The study found that 68.4% of patients in the liberal-strategy group and 73.5% in the restrictive-strategy group experienced an unfavorable outcome (adjusted absolute difference of 5.4 percentage points; 95% CI, −2.9 to 13.7). No significant difference in mortality or depression was observed between the two groups. Although some functional independence and quality of life measures were better in the liberal group among survivors, venous thromboembolic events and acute respiratory distress syndrome rates were comparable.
Implications for Practice: The findings indicate that a liberal transfusion strategy does not significantly improve neurologic outcomes at 6 months in critically ill TBI patients compared to a restrictive strategy. Clinicians may consider maintaining a restrictive transfusion strategy, given the similar outcomes and potential for fewer transfusions. Further research is needed to explore specific subgroups that might benefit from different transfusion strategies.
Randomized Controlled Trial: Mixed results with Andexanet Alfa for Factor Xa inhibitor-associated acute intracerebral hemorrhage – N Engl J Med
27 May, 2024 | 20:26h | UTCStudy Design and Population: This randomized controlled trial involved 530 patients with acute intracerebral hemorrhage who had taken factor Xa inhibitors within 15 hours before the event. They were randomly assigned to receive either andexanet alfa or usual care.
Main Findings: Hemostatic efficacy was achieved in 67% of patients receiving andexanet compared to 53.1% receiving usual care. Andexanet significantly reduced anti-factor Xa activity by 94.5%, compared to 26.9% with usual care. However, thrombotic events were more frequent in the andexanet group, including ischemic stroke.
Implications for Practice: Andexanet alfa is effective in controlling hematoma expansion in patients with factor Xa inhibitor-associated intracerebral hemorrhage but has an increased risk of thrombotic events. Further research is needed to balance efficacy and safety.
Reference (link to abstract – $ for full-text):
Randomized Clinical Trial: Aficamten improves peak oxygen uptake in symptomatic obstructive hypertrophic cardiomyopathy – N Engl J Med
27 May, 2024 | 20:24h | UTCStudy Design and Population: This phase 3, double-blind trial randomized 282 adults with symptomatic obstructive hypertrophic cardiomyopathy (HCM) to receive aficamten or placebo for 24 weeks. The primary outcome was the change in peak oxygen uptake, with secondary outcomes including changes in the Kansas City Cardiomyopathy Questionnaire score and New York Heart Association functional class.
Main Findings: Aficamten significantly increased peak oxygen uptake by 1.7 ml/kg/min (95% CI, 1.0 to 2.4; P<0.001) compared to placebo. Improvements were also seen in all secondary outcomes. The incidence of adverse events was similar between the groups.
Implications for Practice: Aficamten shows promise in improving exercise capacity and symptoms in patients with obstructive HCM, potentially offering a new therapeutic option. Further research may confirm its long-term benefits and safety.
Reference (link to abstract – $ for full-text):
Randomized Clinical Trial: Dequalinium chloride demonstrates noninferiority to metronidazole in treating bacterial vaginosis – JAMA Netw Open
25 May, 2024 | 19:55h | UTCThis randomized clinical trial investigated the efficacy of dequalinium chloride compared to metronidazole for treating bacterial vaginosis in premenopausal women. Conducted across multiple centers from July 2021 to August 2022, the study involved 147 participants who were randomly assigned to receive either dequalinium chloride vaginal tablets or oral metronidazole. The primary outcome measured was the clinical cure rate shortly after treatment completion. Results showed that dequalinium chloride achieved a 92.8% cure rate, which was statistically noninferior to metronidazole’s 93.2% rate. Additionally, dequalinium chloride was better tolerated, with fewer adverse events reported compared to metronidazole. These findings suggest that dequalinium chloride is as effective as traditional antibiotic treatments for bacterial vaginosis and could be considered a viable non-antibiotic alternative due to its similar efficacy and enhanced tolerability.
Reference (link to free full-text):
RCT: Thrombectomy improves outcomes in acute stroke with large infarcts – N Engl J Med
25 May, 2024 | 19:35h | UTCStudy Design and Population: This randomized clinical trial investigated the efficacy of thrombectomy in combination with standard medical care versus medical care alone in patients with acute stroke and large infarcts. Participants included 333 patients with proximal cerebral vessel occlusion in the anterior circulation, presenting within 6.5 hours of symptom onset. They were randomized in a 1:1 ratio to either undergo thrombectomy or receive only medical care. An Alberta Stroke Program Early Computed Tomographic Score of ≤5 was used to define large infarcts.
Main Findings: The primary outcome, assessed by the modified Rankin scale score at 90 days, showed a median score of 4 in the thrombectomy group compared to 6 in the control group, indicating better functional outcomes with thrombectomy (generalized odds ratio, 1.63; 95% CI, 1.29 to 2.06; P<0.001). Mortality at 90 days was significantly lower in the thrombectomy group (36.1%) compared to the control group (55.5%) with an adjusted relative risk of 0.65. However, thrombectomy was associated with a higher rate of symptomatic intracerebral hemorrhage (9.6% vs. 5.7% in the control group).
Implications for Practice: The findings suggest that thrombectomy, when added to standard medical care, can significantly improve functional outcomes and reduce mortality in patients with large infarct strokes. However, the increased risk of symptomatic intracerebral hemorrhage must be considered when deciding on this intervention. These results support the broader use of thrombectomy in clinical settings with similar patient profiles but underscore the need for careful risk-benefit analysis due to the potential for serious hemorrhagic complications.
Reference (link to abstract – $ for full-text):
RCT: Ponatinib shows superior MRD-negative complete remission rates compared to Imatinib in newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia – JAMA
25 May, 2024 | 19:03h | UTCThis global phase 3 randomized clinical trial investigated the efficacy and safety of ponatinib versus imatinib in adults with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL). The study, conducted across 77 sites, enrolled 245 patients who were randomized in a 2:1 ratio to receive either ponatinib (30 mg/d) or imatinib (600 mg/d) alongside reduced-intensity chemotherapy. The primary endpoint of the trial was minimal residual disease–negative (MRD-negative) complete remission, assessed at the end of cycle 3. Results showed that ponatinib achieved a significantly higher MRD-negative complete remission rate of 34.4% compared to 16.7% with imatinib. Additionally, the safety profile between the two drugs was comparable, with arterial occlusive events being rare and similar across groups. These findings suggest ponatinib as a potentially preferable frontline therapy in this patient population due to its superior efficacy in achieving MRD-negative status without compromising safety.
Reference (link to abstract – $ for full-text):
RCT: Impact of single PSA screening invitation on 15-year prostate cancer mortality – JAMA
25 May, 2024 | 19:01h | UTCStudy Design and Population: This study is a secondary analysis of the Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP), which focused on the long-term effects of prostate-specific antigen (PSA) screening on prostate cancer mortality. It involved 415,357 men aged 50 to 69 years from 573 primary care practices across England and Wales. Participants were randomized to either receive a single invitation for a PSA screening or to a control group receiving standard practice without invitation. The follow-up period concluded on March 31, 2021, after a median duration of 15 years.
Main Findings: The intervention group, which received one PSA screening invitation, showed a prostate cancer mortality rate of 0.69% compared to 0.78% in the control group, translating to a rate ratio of 0.92 and demonstrating a statistically significant but modest reduction in death from prostate cancer. Additionally, the screening led to increased detection rates of low-grade and localized prostate cancer. However, there were no significant differences in detection of more advanced cancer stages between the two groups. All-cause mortality rates were similar across both groups.
Implications for Practice: While the introduction of a single PSA screening invitation was associated with a slight decrease in prostate cancer mortality over 15 years, the absolute reduction was small. These findings suggest that while PSA screening can detect cancer earlier, its impact on long-term survival is limited and should be weighed against the potential for overdiagnosis and overtreatment. Future strategies in prostate cancer screening might need to focus more on risk stratification and personalized screening approaches to maximize benefits and minimize unnecessary interventions.
Reference (link to abstract – $ for full-text):
RCT: Omission of axillary dissection noninferior to complete dissection in clinically node-negative breast cancer with sentinel-node metastases – N Engl J Med
25 May, 2024 | 18:57h | UTCStudy Design and Population: This noninferiority trial explored the effects of omitting completion axillary-lymph-node dissection in patients with clinically node-negative primary T1 to T3 breast cancer who had one or two sentinel-node macrometastases. A total of 2766 patients were enrolled and randomized 1:1 to either undergo sentinel-node biopsy only or completion dissection. Patients received adjuvant treatment and radiation therapy as per national guidelines, focusing on recurrence-free survival as a secondary end point.
Main Findings: The study reported that the 5-year recurrence-free survival rates were 89.7% in the sentinel-node biopsy-only group and 88.7% in the dissection group, with a country-adjusted hazard ratio for recurrence or death at 0.89 (95% CI, 0.66 to 1.19), significantly below the noninferiority margin (P<0.001). This outcome demonstrates the noninferiority of the less invasive sentinel-node biopsy approach compared to the traditional dissection method in managing sentinel-node macrometastases.
Implications for Practice: The findings suggest that for clinically node-negative breast cancer patients with sentinel-node macrometastases, omitting axillary-lymph-node dissection could be considered a viable treatment option, potentially reducing the surgical burden without compromising recurrence-free survival outcomes. This could lead to adjustments in surgical practice and patient care strategies, emphasizing a less invasive approach while maintaining clinical efficacy.
Reference (link to abstract – $ for full-text):
RCT: Laparoscopic hemihepatectomy for primary or metastatic cancer offers faster recovery and improved quality of life compared to open surgery – J Clin Oncol
25 May, 2024 | 18:52h | UTCStudy Design and Population: This study was a multicenter, randomized controlled, patient-blinded, superiority trial involving adult patients undergoing major liver resection (hemihepatectomy) primarily for cancer. Conducted across 16 European hospitals from November 2013 to December 2018, it included 352 patients who were randomized, with 332 completing the surgery—166 each in the laparoscopic and open surgery groups.
Main Findings: The primary outcome, time to functional recovery, was significantly shorter for the laparoscopic group, averaging 4 days compared to 5 days for the open surgery group (P < .001). Quality of life assessments showed higher scores for global health status and body image in the laparoscopic group. Although major complication rates were similar between the two groups, the laparoscopic approach demonstrated a notable advantage in the secondary cancer-specific outcome of time to adjuvant systemic therapy, which was significantly shorter compared to the open surgery group.
Implications for Practice: The findings suggest that laparoscopic hemihepatectomy not only enhances functional recovery and quality of life but also accelerates the initiation of adjuvant therapy in cancer patients without compromising safety or oncological outcomes. This evidence supports the broader adoption of laparoscopic techniques in major liver resections, particularly for cancer-related surgeries, to improve postoperative recovery and patient well-being.
Reference (link to abstract – $ for 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):
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):
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):
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):
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):
RCT: Early patching proves more effective than extended optical treatment in pediatric amblyopia management – The Lancet
5 May, 2024 | 15:00h | UTCStudy Design and Population:
The EuPatch study was a multicenter, randomized controlled trial conducted across 30 hospitals in multiple European countries, including the UK, Greece, Austria, Germany, and Switzerland. It targeted children aged 3–8 years diagnosed with amblyopia due to anisometropia, strabismus, or both, with an interocular difference ≥0.30 logMAR in best corrected visual acuity (BCVA). Participants were divided into two groups: one underwent 18 weeks of glasses use before patching (Extended Optical Treatment, EOT), and the other just 3 weeks (early patching), each supplemented with an intensive patching regimen.
Main Findings:
Out of the 334 initially randomized participants, 317 were analyzed for the primary outcome. The early patching group demonstrated a significantly higher success rate, achieving ≤0.20 logMAR interocular difference in BCVA in 67% of cases compared to 54% in the EOT group after 12 weeks of patching (p=0.019). The median follow-up times were 42 weeks for the EOT group and 27 weeks for the early patching group, with dropout rates of 14% and 6%, respectively.
Implications for Practice:
The findings suggest that early patching is superior to EOT in the management of amblyopia in children, presenting a viable option for enhancing treatment effectiveness. This study supports the potential personalization of amblyopia treatments based on the quicker onset of patching. These results could influence future guidelines and clinical practices in pediatric ophthalmology.
Reference (link to free full-text):
RCT: Xanomeline-trospium reduces psychosis symptoms in patients with schizophrenia – JAMA Psychiatry
2 May, 2024 | 23:24h | UTCStudy Design and Population:
This study, titled EMERGENT-3 (NCT04738123), is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial conducted to evaluate the efficacy and safety of xanomeline-trospium chloride in adults with schizophrenia experiencing acute psychosis. It involved 256 participants across 30 inpatient sites in the US and Ukraine, with the study period running from April 1, 2021, to December 7, 2022. Data analysis occurred from February to June 2023.
Main Findings:
The primary outcome was the change from baseline to week 5 in the Positive and Negative Syndrome Scale (PANSS) total score. Xanomeline-trospium significantly reduced the PANSS total score compared to placebo, with a least squares mean difference of -8.4 and a Cohen’s d effect size of 0.60. The most common adverse events were gastrointestinal, mild to moderate in intensity, and generally transient. Safety and tolerability profiles were favorable, with similar discontinuation rates due to adverse events between the xanomeline-trospium and placebo groups.
Implications for Practice:
The results of EMERGENT-3, alongside the consistent findings from earlier phases of the trial, affirm xanomeline-trospium’s potential as a novel class of antipsychotic medication. Its mechanism of action, which does not involve D2 dopamine receptor blocking, offers a promising alternative to traditional antipsychotics, particularly for patients who may benefit from different therapeutic approaches due to issues with current treatments.
Commentary on X:
Xanomeline-trospium is efficacious & well tolerated in people with schizophrenia experiencing acute psychosis, finds EMERGENT-3 trial, and supports potential of xanomeline-trospium to be first in a putative new class of antipsychotic medications. https://t.co/ioBCKOgvQa pic.twitter.com/CDmYEgYN2O
— JAMA Psychiatry (@JAMAPsych) May 1, 2024
Reference (link to free full-text):
RCT: Radiation therapy alone superior to chemoradiation in low-grade localized endometrial cancer recurrences
1 May, 2024 | 21:41h | UTCThis randomized clinical trial assessed the effectiveness of radiation therapy alone versus concurrent chemoradiation in treating localized recurrences of endometrial cancer. Conducted from February 2008 to August 2020, the study involved 165 patients who were randomized to receive either radiation therapy alone or chemoradiation with weekly cisplatin. Findings indicate that radiation therapy alone resulted in longer progression-free survival (PFS) compared to chemoradiation, with a median PFS not reached for radiation alone versus 73 months for chemoradiation. Additionally, radiation therapy demonstrated lower rates of acute toxicity. The study concluded that for patients with low-grade and primarily vaginal recurrences, radiation therapy alone is the preferable treatment option, offering excellent outcomes without the added toxicity of chemotherapy.
Reference (link to abstract – $ for full-text):
RCT: Aspirin fails to improve invasive disease-free survival in breast cancer patients
1 May, 2024 | 21:37h | UTCThis randomized clinical trial assessed the efficacy of daily aspirin (300 mg) as adjuvant therapy in reducing breast cancer recurrence among 3020 participants with high-risk nonmetastatic breast cancer across the United States and Canada. The study, which followed participants for a median of 33.8 months, found no significant benefit of aspirin on invasive disease-free survival or overall survival, with the hazard ratio for disease-free survival being 1.27 (95% CI, 0.99-1.63; P = .06) and for overall survival 1.19 (95% CI, 0.82-1.72). Given these findings, aspirin is not recommended as an adjuvant treatment for breast cancer, challenging earlier observational data that suggested a potential survival benefit in breast cancer survivors. The trial was concluded early due to the lack of observed benefits, with adverse event rates being similar in both the aspirin and placebo groups.
Commentary on X:
Among participants with high-risk nonmetastatic breast cancer, daily aspirin therapy did not improve risk of breast cancer recurrence or survival in early follow-up. https://t.co/uPWTeaqXdJ pic.twitter.com/x6Qb4bRlqF
— JAMA (@JAMA_current) April 29, 2024
Reference (link to abstract – $ for full-text):
RCT: Beta-blockers post myocardial infarction showed no benefit in patients with preserved ejection fraction
30 Apr, 2024 | 13:40h | UTCThis randomized, open-label clinical trial conducted across 45 centers in Sweden, Estonia, and New Zealand examined the impact of long-term beta-blocker treatment in patients with acute myocardial infarction (AMI) who had undergone coronary angiography and had a preserved left ventricular ejection fraction (LVEF ≥ 50%). The study involved 5020 patients, predominantly from Sweden, with a median follow-up of 3.5 years. Participants were randomly assigned to receive either a beta-blocker (metoprolol or bisoprolol) or no beta-blocker. The primary endpoint was a composite of death from any cause or new myocardial infarction. The results showed no significant difference in the primary endpoint between the beta-blocker group (7.9%) and the no–beta-blocker group (8.3%) with a hazard ratio of 0.96 (95% CI, 0.79 to 1.16; P=0.64). Additionally, no significant differences were observed in secondary endpoints such as death from cardiovascular causes, myocardial infarction, or hospitalizations for atrial fibrillation and heart failure. Safety endpoints were also comparable between the groups. Overall, long-term beta-blocker treatment did not confer a reduction in risk for the primary composite endpoint or improve secondary outcomes in this patient population.
Commentary on X:
Original Article: Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction (REDUCE-AMI trial) https://t.co/z1NNeAK9Mm
Editorial: Routine Beta-Blockers in Secondary Prevention — On Injured Reserve https://t.co/NzlExH0LZm #ACC24 pic.twitter.com/8Jqpj2dM6E
— NEJM (@NEJM) April 17, 2024
Reference (link to abstract – $ for full-text):
RCT: No benefit of Apolipoprotein A1 infusions in preventing cardiovascular events post-myocardial infarction
29 Apr, 2024 | 12:42h | UTCThis international, double-blind, placebo-controlled trial investigated the effect of apolipoprotein A1 (CSL112) infusions on cardiovascular outcomes in patients with recent acute myocardial infarction and multivessel coronary disease. A total of 18,219 patients were randomized to receive either four weekly 6 g infusions of CSL112 or a placebo within five days of initial medical contact. Over 90, 180, and 365 days, the trial found no significant difference in the risk of myocardial infarction, stroke, or cardiovascular death between the two groups. Additionally, adverse events were similar across groups, though hypersensitivity was more common in the CSL112 group.
Reference (link to abstract – $ for full-text):
RCT: Semaglutide significantly improves symptoms and weight loss in HFpEF and type 2 diabetes patients
29 Apr, 2024 | 12:36h | UTCThis randomized clinical trial evaluated the effects of semaglutide on 616 patients with obesity-related heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes. Patients received weekly doses of 2.4 mg semaglutide or a placebo for 52 weeks. The study’s primary findings included a significant improvement in heart failure–related symptoms, as measured by the Kansas City Cardiomyopathy Questionnaire clinical summary score (average increase of 13.7 points in the semaglutide group versus 6.4 points in the placebo group). Additionally, semaglutide treatment resulted in a mean 9.8% reduction in body weight compared to 3.4% with placebo. Secondary outcomes also favored semaglutide, showing enhancements in 6-minute walk distance and reductions in C-reactive protein levels. Notably, semaglutide was associated with fewer serious adverse events compared to placebo.
Reference (link to abstract – $ for full-text):