Podcasts about Subgroup

Immunic Inc (NASDAQ:IMUX) president and chief operating officer Jason Tardio joined Proactive's Stephen Gunnion from the BIO International Convention in Boston with more on recent clinical developments. Tardio highlighted Immunic's ongoing business development efforts, particularly around its lead asset, vidofludimus calcium, aimed at treating multiple sclerosis (MS). Tardio described the compound as the first dual-mechanism treatment in development for MS, addressing both neuroinflammation and neurodegeneration. He explained, “Vidofludimus calcium is a highly selective DHODH inhibitor and also the first medicine in development that's an activator of Nurr1, which we know will provide neuroprotective benefits.” The recent Phase 2 CALLIPER trial in progressive MS involved 467 patients and showed a 24% reduction in confirmed disability worsening versus placebo. Subgroup analysis showed up to a 35% reduction in disability in primary progressive MS patients without inflammatory disease activity—a group previously lacking effective treatment options. Tardio also discussed the company's Phase 3 ENSURE trials in relapsing MS, which have now completed enrollment with over 1,100 patients each. Topline results are expected in the latter part of 2026. Beyond clinical developments, he commented on industry themes at the conference, including funding challenges and a shared focus on patient-driven innovation. For more interviews and updates, visit Proactive's YouTube channel. Don't forget to like the video, subscribe to the channel, and enable notifications for future content. #Immunic #MultipleSclerosis #MSResearch #BiotechNews #VidofludimusCalcium #ProgressiveMS #Neurodegeneration #BIO2025 #PharmaInnovation #ClinicalTrials

N Engl J Med 1991;325:293-302N Engl J Med 1992;327:685-691Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Background: Systolic heart failure affects millions worldwide and is associated with high mortality and morbidity. If left untreated, the one-year mortality ranges from 15-50%, depending on the severity of the disease.The CONSENSUS trial found mortality benefit with the use of the angiotensin converting enzyme inhibitor (ACEi) enalapril in patients with New York Heart Association (NYHA) class IV heart failure. Data on less severe heart failure were lacking.The Studies of Left Ventricular Dysfunction (SOLVD) sought to assess whether an ACEi, enalapril, would reduce mortality in patients with low left ventricular ejection fractions defined as 35% of less.Patients: Eligible patients had left ventricular ejection fraction of 35% or less. The ejection fraction was measured using radionuclide techniques in 68% of the patients, contrast angiography in 11%, and two-dimensional echocardiography in 21%.Patients were excluded if they were over 80 years of age, or if they had significant valvular disease requiring surgery, unstable angina pectoris, angina requiring revascularization procedures, myocardial infarction during the previous month, severe pulmonary disease, serum creatinine >2 mg/ dl, or any other disease that might significantly impact survival.At the end of the run-in period for placebo, patients who had overt congestive heart failure were enrolled in the Treatment trial, and patients who were not having overt congestive heart failure were enrolled in the Prevention trial.Baseline characteristics: Patients were recruited from 83 hospitals linked to 23 centers in the United States, Canada, and Belgium.The Treatment trial randomized 2,569 patients – 1,285 patients randomized to receive enalapril and 1,284 randomized to receive placebo. The average age of patients was 61 years and 80% were men. The average left ventricular ejection fraction was 25%. Approximately 42% had hypertension, 26% had diabetes, 71% had ischemic heart disease and 22% were current smokers. The NYHA class was I in 11% of the patients, II in 57% of the patients, III in 30% and IV 2%. At the time of enrollment, 8% were taking beta-blockers, 67% were taking digitalis, 85% were taking diuretics, 9% were taking potassium-sparing diuretics and 51% were taking vasodilators (other than ACEi).The Prevention trial randomized 4,228 patients – 2,111 patients randomized to receive enalapril and 2,117 randomized to receive placebo. The average age of patients was 59 years and 89% were men. The average left ventricular ejection fraction was 28%. Approximately 37% had hypertension, 15% had diabetes, 83% had ischemic heart disease and 23% were current smokers. The NYHA class was I in 67% of the patients and II in 33%. At the time of enrollment, 24% were taking beta-blockers, 12% were taking digitalis, 17% were taking diuretics, 4% were taking potassium-sparing diuretics and 46% were taking vasodilators (other than ACEi).Procedures: A total of 7,402 patients were deemed eligible across both the Treatment and Prevention trials.Eligible patients for either trial entered a run-in and stabilization phase. Patients were given enalapril 2.5 mg twice daily in a single-blind fashion for 2 - 7 days to identify patients who could not tolerate even a small dose of the drug or those who were unable to comply with the regimen. A total of 310/7402 patients (4.2%) were excluded from the study during this phase. Following the active dosing phase, patients were placed on a regimen of matching placebo in a single-blind manner for 14 - 17 days. This allowed identification of individuals whose clinical condition deteriorated after drug withdrawal or who demonstrated poor compliance. During this phase, 295/ 7,092 patients (4.2%) were excluded from the study.At the end of the run-in period for placebo, patients who had overt congestive heart failure were enrolled in the Treatment trial, and patients who were not having overt congestive heart failure were enrolled in the Prevention trial.After that patients were randomized in a 1:1 ratio to receive enalapril or placebo.Treatment with enalapril or placebo was initiated at 2.5 mg or 5 mg twice daily, based on the patient's clinical status and physician judgment. The dose was titrated up to 10 mg twice daily if tolerated without symptomatic hypotension or worsening renal function. After randomization, follow-up visits occurred at two weeks, six weeks, four months, and every four months thereafter until study completion.Endpoints: The primary outcome for both trials was all-cause mortality. Heart failure hospitalization was assessed as a secondary outcome.The estimated sample size was 2,500 patients for the treatment trial and 4,600 for the prevention trial. These sample sizes would provide 90% power at 5% two-sided alpha to detect 25% relative risk reduction in mortality, with the use of enalapril. The estimated 3-year mortality in the control group was 32% in the Treatment trial and 17% in the Prevention trial.Authors reported risk reduction which was calculate as (1 – relative risk)*100.Results: A total of 39,924 patients with a left ventricular ejection fraction of 35% or less were identified. Of these, 6.4% were enrolled in the Treatment trial and 7.4% in the Prevention trial. Among the excluded patients, the main reasons were prior use of an ACEi (28%), cardiovascular problems (12%), contraindications to using ACEi (11%), lack of patient consent (11%), administrative reasons (21%), cancer or other life-threatening illnesses (12%), and other miscellaneous reasons (5%).The average follow up time was 41.4 months in the Treatment trial and 37.4 months in the Prevention trial.In the Treatment trial, enalapril reduced all-cause mortality (35.2% vs 39.7%, risk reduction: 16%, 95% CI: 5% – 26%; p< 0.0036). The majority of deaths (89%) were cardiovascular and the majority of these (79%) were heart failure or arrhythmia related. Enalapril also reduced all-cause hospitalization (69.5% vs 74.0%; p= 0.006). The total number of hospitalizations for heart failure was also reduced with enalapril – 683 vs 971. Subgroup analysis showed a numerical increase in death, with enalapril, in patients with an ejection fraction of 30-35% - this was not statistically significant.In the Prevention trial, enalapril did not have a significant effect on mortality (14.8% with enalapril vs 15.8% with placebo, risk reduction: 8%, 95% CI: -8% – 21%; p= 0.30). Enalapril significantly reduced the development of heart failure (20.7% vs 30.2%; p< 0.001). Total number of hospitalizations for heart failure was also significantly reduced with enalapril – 306 vs 454. The reduction in the development of heart failure was seen across all ejection fractions below 35%, although the benefit was larger with lower ejection fractions.In both trials, the benefit of enalapril was seen early after treatment initiation.Conclusion: In patients with left ventricular ejection fraction of 35% or less and overt congestive heart failure, enalapril reduced all-cause mortality with a number needed to treat of approximately 22 patients. In patients with a left ventricular ejection fraction of 35% or less and without overt congestive heart failure, enalapril had no significant effect on mortality but it reduced the development of heart failure with an number needed to treat of approximately 11 patients.The SOLVD trials provide strong evidence supporting the use of ACEi in patients with systolic heart failure. The role of ACEi in systolic heart failure has been examined across diverse patient groups, and the totality of evidence consistently supports their use. However, when examining the SOLVD trials in isolation, it is important to recognize the selective nature of enrollment, which limits the trials' external validity. Additionally, the use of a run-in period introduces bias in favor of enalapril, although this concern is less significant when the primary outcome is all-cause mortality.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

N Engl J Med 2017;377:2419-2432Background: A small fraction of patients with acute myocardial infarction (5-10%) have cardiogenic shock. These patients have a high baseline mortality. Early revascularization had been established as better than initial stabilization with medical therapy. Many patients with cardiogenic shock due to acute myocardial infarction (AMI) have multivessel disease. The question arises about whether to do culprit-only percutaneous coronary intervention (PCI) or more complete PCI at the time of the initial intervention.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.The Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock (CULPRIT-SHOCK) trial was designed to test the hypothesis that PCI of the culprit lesion only, with the option of staged revascularization of nonculprit lesions, would result in better clinical outcomes than immediate multivessel PCI among patients who have multivessel coronary artery disease and acute myocardial infarction with cardiogenic shock.Patients: The trial enrolled 706 patients with acute myocardial infarction (ST-segment elevation or non-ST-segment elevation) complicated by cardiogenic shock who had multivessel coronary artery disease. Cardiogenic shock was defined as SBP < 90 mmHg for more than 30 minutes or requiring pressors, clinical signs of pulmonary congestion, and signs of organ hypoperfusion (altered mental status, cold/clammy skin, oliguria, or lactate > 2 mmol/L).Exclusion criteria were extensive and designed to exclude patients with extremely poor prognosis: prolonged resuscitation, no intrinsic heart action, fixed dilated pupils, an indication for urgent CABG, a mechanical cause of shock, age > 90 years, massive pulmonary embolism, or severe renal insufficiency at baseline.Baseline Characteristics: The median age was 70 years, and approximately 75% were male. About 63% of patients had three-vessel disease. More than half the patients had ST-segment elevation myocardial infarction (about 62%), and anterior ST-segment elevation MI accounted for approximately 54% of these cases. About 53% of patients required resuscitation before randomization. The median left ventricular ejection fraction was between 30-33%.Procedures: In the culprit-lesion-only PCI group, only the culprit lesion was treated during the initial procedure, with staged revascularization encouraged based on residual ischemic lesions. In the multivessel PCI group, PCI of all major coronary arteries with >70% stenosis was performed, including attempts to recanalize chronic total occlusions. Crossover from the culprit-lesion-only PCI group to the multivessel PCI group occurred in 12.5% of patients, while crossover in the opposite direction happened in 9.4% of patients. The overall dose of contrast material was significantly higher and the duration of fluoroscopy significantly longer in the multivessel PCI group. Other interventional therapeutic measures were allowed, independent of the assigned treatment strategy.Endpoints: The primary endpoint was a composite of death from any cause or severe renal failure leading to renal-replacement therapy within 30 days after randomization. Secondary endpoints included the individual components of the primary endpoint, recurrent myocardial infarction, rehospitalization for heart failure, repeat revascularization, time to hemodynamic stabilization, catecholamine therapy duration, ICU stay duration, and measurements of renal and myocardial injury. Safety end points included bleeding, which was defined as type 2, 3, or 5 on the Bleeding Academic Research Consortium (BARC) scale.Trialists estimated an event rate of the composite primary endpoint of 38% in the culprit-only group vs 50% in the complete group. Using a global type I error level of 0.05, the authors calculated that a sample of 684 patients would give the trial 80% power to rule out the null hypothesis of no difference between the two treatment groups in the event rate for the primary end point.Results: At 30 days, the composite primary endpoint occurred in 45.9% of patients in the culprit-lesion-only PCI group versus 55.4% in the multivessel PCI group (relative risk, 0.83; 95% CI, 0.71 to 0.96; P=0.01). Death occurred in 43.3% of the culprit-lesion-only PCI group versus 51.6% of the multivessel PCI group (relative risk, 0.84; 95% CI, 0.72 to 0.98; P=0.03). The rate of renal-replacement therapy was 11.6% in the culprit-lesion-only PCI group and 16.4% in the multivessel PCI group (relative risk, 0.71; 95% CI, 0.49 to 1.03; P=0.07).Rates of recurrent myocardial infarction, rehospitalization for heart failure, bleeding, and stroke did not differ significantly between groups. Subgroup analyses showed consistent results across all prespecified subgroups. The time to hemodynamic stabilization, the use of catecholamine therapy and the duration of such therapy, the duration of the ICU stay, and the use of mechanical ventilation and the duration of such therapy also did not differ significantly between the two groups.Conclusion: In patients with myocardial infarction and cardiogenic shock, culprit-only PCI was superior to multivessel PCI. Both components of the primary endpoint, death and severe renal failure were lower in the culprit-only arm. The authors and editorialists speculate why these findings contrast with trials in hemodynamically stable myocardial infarction patients, where early multivessel PCI showed benefit over culprit-only PCI.If you accept the thesis that multi-vessel PCI was superior to culprit-only PCI in stable AMI patients, the likely reason for the disparate results are that patients with cardiogenic shock differ substantially from stable patients. The sicker patients with cardiogenic shock benefit from a less-is-more approach where culprit-only PCI reduces treatment harm relative to multivessel PCI.We at CardiologyTrials, however, find the evidence for complete revascularization in stable AMI patients less than clear. The COMPLETE trial found benefit from multivessel PCI over culprit-only, but both composite endpoints were driven largely by non-fatal MI. CV death was not substantially different. The difference in MI could have been related to excluding procedure-related MI.What's more, the FULL-REVASC trial, which also compared culprit-only and multivessel PCI, failed to replicate the COMPLETE trial results. In FULL-REVASC the rates of the composite primary outcome of death, MI or unplanned revascularization were not significantly different. Sadly, FULL-REVASC was stopped early when COMPLETE results were published, which led to a possible loss of power.It's possible, likely even, that the null results of CULPRIT-SHOCK are not really that disparate from prior trials in patients with more stable AMI.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Commentary by Dr. Jian'an Wang.

The Lancet 2002;360:743-751Background: The TACTICS-TIMI 18 trial showed that an early invasive strategy in beneficial in selected patients with unstable angina or non-ST-elevation myocardial infarction (NSTEMI). These positive findings contrasted the findings from some earlier studies.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.The British Heart Foundation RITA 3 randomized trial sought to compare invasive vs conservative strategy in patients with unstable angina or NSTEMI, similar to the trial question of TACTICS-TIMI 18.Patients: Eligible patients had suspected cardiac chest pain at rest with at least one of the following: Evidence of ischemia on electrocardiogram (ST depression, transient ST elevation, old left bundle branch block, or T wave inversion), pathologic Q waves suggesting previous myocardial infarction, or documented coronary artery disease on prior coronary angiogram.Patients were excluded if they had evolving myocardial infarction in which reperfusion therapy was indicated. Patients were also excluded if creatine kinase or creatine kinase MB concentrations were twice the upper limit of normal before randomization, if they had myocardial infarction within a month, had percutaneous coronary intervention (PCI) in the previous 12 months, or coronary artery bypass grafting (CABG) at any time.Baseline characteristics: The trial randomized 1,810 patients – 895 randomized to the invasive strategy and 915 randomized to conservative strategy. Patients were recruited from 45 hospitals in England and Scotland.The average age of patients was 63 years and 62% were men. Approximately 35% had hypertension on drugs, 13% had diabetes and 28% had prior myocardial infarction.The majority (92%) of the patients were enrolled because they met the criteria for evidence of ischemia on electrocardiogram.Procedures: Patients were randomly assigned in a 1:1 ratio to undergo invasive vs conservative strategy.In the conservative arm, patients received aspirin and enoxaparin 1mg/kg subcutaneously twice a day for 2-8 days. Beta-blockers, other antiplatelets and glycoprotein IIb/IIIa inhibitors could also be used. Coronary angiography could be performed if patients had anginal symptoms at rest or with minimal exertion despite appropriate therapy or if they had ischemia on stress testing.Patients in the invasive strategy arm received similar medical therapy to the conservative arm. Coronary angiogram was to be performed as soon as possible after randomization and ideally within 72 hours. Revascularization was recommended for lesions of at least 70% stenosis or 50% or more if left main.Endpoints: The trial had two co-primary outcomes. The first was a composite of death from any cause, nonfatal myocardial infarction, or refractory angina at 4 months. The second was a composite of death from any cause or nonfatal myocardial infarction at 1 year.Analysis was performed based on the intention-to-treat principle. The estimated sample size to provide 80% power at 5% alpha, was 1,770 patients. This assumed that 12% of the patients in the conservative arm would experience the outcome of death or non-fatal myocardial infarction at 1-year, and that the invasive strategy would result in 33% relative risk reduction in this outcome.Results: In the invasive strategy, 97% of the patients underwent coronary angiogram at a median of 2 days after randomization, and 55.3% underwent PCI or CABG. In the conservative arm, 10.3% had revascularization during the index admission, and 17.3% had revascularization at 1-year. The median follow time was 2 years and 97% of the patients had at least 1-year of follow up.The first primary composite outcome of death from any cause, nonfatal myocardial infarction, or refractory angina at 4 months was lower with the invasive strategy (9.6% vs 14.5%, HR: 0.66, 95% CI: 0.51 – 0.85; p= 0.001). The second primary composite outcome of death from any cause or nonfatal myocardial infarction at 1 year was not significantly different between both groups (7.6% with invasive vs 8.3% with conservative, HR: 0.91, 95% CI: 0.67 – 1.25; p= 0.58). At 1-year, 4.6% patients died in the invasive arm compared to 3.9% in the conservative arm, and this was not statistically significant. Myocardial infarction at 1-year occurred in 3.8% of the patients in the invasive arm compared to 4.8% in the conservative arm, and this was not statistically significant as well.All bleeding occurred in 8.2% in the invasive arm and 3.5% in the conservative arm.Subgroup analysis showed that men benefited from an invasive strategy while women did not (p for interaction= 0.011). The endpoint of death or myocardial infarction at 1-year, in women, was 5.1% in the conservative arm and 8.6% in the invasive arm, while in men, the incidence of this endpoint was 10.1% in the conservative arm and 7.0% in the invasive arm.Conclusion: In patients with unstable angina or NSTEMI, an invasive strategy compared to conservative strategy, reduced refractory angina but not myocardial infarction or death at 1-year.The reduction in angina is a subjective endpoint, prone to bias and faith healing, as we have previously discussed in other trials of PCI. The reduction in this endpoint alone should not justify widespread adoption of invasive strategy for unstable angina or NSTEMI.A key distinction between this trial and TACTICS-TIMI 18—which demonstrated a reduction in myocardial infarction with an invasive approach—is that this study included patients with smaller myocardial infarctions. Only 41% of participants had ST depression or transient ST elevation, and patients were excluded if creatine kinase or creatine kinase MB levels were more than twice the upper limit of normal before randomization. This highlights the heterogeneity among patients with unstable angina and NSTEMI, where baseline risk and the extent of myocardial necrosis influence treatment effects. We encourage you to read again the subgroup interactions of TACTICS-TIMI 18.Additionally, in the current era, high-sensitivity troponin assays enable the detection of smaller myocardial infarctions, potentially limiting the applicability of older trial results to all present NSTEMI patients.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Featuring an interview with Dr Komal Jhaveri, including the following topics: Imlunestrant, an oral selective estrogen receptor degrader (SERD), with and without abemaciclib for ER-positive, HER2-negative advanced or metastatic breast cancer (0:00) Jhaveri KL et al. Imlunestrant, an oral selective estrogen receptor degrader (SERD), as monotherapy & combined with abemaciclib, for patients with ER+, HER2- advanced breast cancer (ABC), pretreated with endocrine therapy (ET): Results of the phase 3 EMBER-3 trial. San Antonio Breast Cancer Symposium 2024;Abstract GS1-01. Jhaveri KL et al. Imlunestrant with or without abemaciclib in advanced breast cancer. N Engl J Med 2024;[Online ahead of print]. Abstract Rugo HS et al. Elacestrant abemaciclib (abema) combination in patients (pts) with estrogen receptor-positive (ER+), HER2-negative (HER2-) advanced or metastatic breast cancer (mBC). San Antonio Breast Cancer Symposium 2024; Abstract PS7-07. Elacestrant for ER-positive, HER2-negative metastatic breast cancer with ESR1-mutated tumors: Subgroup analyses from the Phase III EMERALD trial by duration of prior endocrine therapy with a CDK4/6 inhibitor and in clinical subgroups (7:40) Bardia A et al. Elacestrant in ER+, HER2- MBC with ESR1-mutated tumors: Subgroup analyses from the phase III EMERALD trial by prior duration of endocrine therapy plus CDK4/6 inhibitor and in clinical subgroups. Clin Cancer Res 2024;30(19):4299-309. Abstract Pharmacokinetics and safety of imlunestrant in patients with hepatic impairment (11:25) Wang XA et al. Evaluation of pharmacokinetics and safety of imlunestrant in participants with hepatic impairment. San Antonio Breast Cancer Symposium 2024;Abstract P4-10-07. Precision therapeutics and emerging strategies for HR-positive metastatic breast cancer (13:15) Lloyd MR et al. Precision therapeutics and emerging strategies for HR-positive metastatic breast cancer. Nat Rev Clin Oncol 2024;21(10):743-61. Abstract CME information and select publications

Dr. Neeraj Agarwal and Dr. Peter Hoskin discuss key abstracts in GU cancers from the 2025 ASCO Genitourinary Cancers Symposium, including novel therapies in prostate, bladder, and kidney cancer and the impact of combination therapies on patient outcomes. TRANSCSRIPT Dr. Neeraj Agarwal: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, the director of the Genitourinary Oncology Program and professor of medicine at the Huntsman Cancer Institute at the University of Utah, and editor-in-chief of ASCO Daily News. Today, we'll be discussing practice-informing abstracts and other key advances in GU oncology featured at the 2025 ASCO Genitourinary Cancers Symposium. Joining me for this discussion is Dr. Peter Hoskin, the chair of this year's ASCO GU Symposium. Dr. Hoskin is a professor in clinical oncology in the University of Manchester and honorary consultant in clinical oncology at the Christie Hospital, Manchester, and University College Hospital London, in the United Kingdom. Our full disclosures are available in the transcript of this episode. Peter, thank you for joining us today. Dr. Peter Hoskin: Thank you so much, Neeraj. I am very pleased to be here. Dr. Neeraj Agarwal: The GU meeting highlighted remarkable advancements across the spectrum of GU malignancies. What stood out to you as the most exciting developments at the ASCO GU Symposium?  Dr. Peter Hoskin: The theme of this year's meeting was "Driving Innovation, Improving Patient Care," and this reflected ASCO GU's incredible milestone in GU cancer research over the years. We were thrilled to welcome almost 6,000 attendees on this occasion from over 70 countries, and most of them were attending in person and not online, although this was a hybrid meeting. Furthermore, we had more than 1,000 abstract submissions. You can imagine then that it fostered fantastic networking opportunities and facilitated valuable knowledge and idea exchanges among experts, trainees, and mentees. So, to start I'd like to come back to you for a second because the first day started with a focus on prostate cancer and some of the key clinical trials. And congratulations to you, Neeraj, on sharing the data from the TALAPRO-2 trial, which we were eagerly awaiting. I'd love to get your thoughts on the data that you presented. Could you tell us more about that trial, Abstract LBA18?  Dr. Neeraj Agarwal: Yes, Peter, I agree with you. It was such an exciting conference overall and thank you for your leadership of this conference. So, let's talk about the TALAPRO-2 trial. First of all, I would like to remind our audience that the combination of talazoparib plus enzalutamide was approved by the U.S. FDA in June 2023 in patients with metastatic castration-resistant prostate cancer harboring HRR gene alterations, after this combination improved the primary endpoint of radiographic progression-free survival compared to enzalutamide alone in the randomized, double-blind, placebo-controlled, multi-cohort phase 3 TALAPRO-2 trial. In the abstract I presented at ASCO GU 2025, we reported the final overall survival data, which was a key alpha-protected secondary endpoint in cohort 1, which enrolled an all-comer population of patients with mCRPC. So, at a median follow-up of around 53 months, in the intention-to-treat population, the combination of talazoparib plus enzalutamide significantly reduced the risk of death by 20% compared to enzalutamide alone, with a median OS of 45.8 months in the experimental arm versus 37 months in the control arm, which was an active control arm of enzalutamide. This improvement was consistent in patients with HRR alterations with a hazard ratio of 0.54 and in those with non-deficient or unknown HRR status, with a hazard ratio of 0.87. In a post hoc analysis, the hazard ratio for OS was 0.78 favoring the combination in those patients who did not have any HRR gene alteration in their tumors by both tissue and ctDNA testing. Consistent with the primary analysis, the updated rPFS data also favored the experimental arm with a median rPFS of 33.1 compared to 19.5 months in the control arm, and a hazard ratio of 0.667. No new safety signals were identified with extended follow-up. Thus, TALAPRO-2 is the first PARP inhibitor plus ARPI study to show a statistically significant and a clinically meaningful improvement in OS compared to standard-of-care enzalutamide as first-line treatment in patients with mCRPC unselected for HRR gene alterations. Dr. Peter Hoskin: Thank you, Neeraj. That's a great summary of the data presented and very important data indeed. There was another abstract also featured in the same session, Abstract 20, titled “Which patients with metastatic hormone-sensitive prostate cancer benefit more from androgen receptor pathway inhibitors? STOPCAP meta-analyses of individual participant data.” Neeraj, could you tell us more about this abstract? Dr. Neeraj Agarwal: Absolutely, I would be delighted to. So, in this meta-analysis, Dr. David Fischer and colleagues pooled individual participant data from different randomized phase 3 trials in the mHSPC setting to assess the potential ARPI effect modifiers and determine who benefits more from an ARPI plus ADT doublet. The primary outcome was OS for main effects and PFS for subgroup analyses. Prostate cancer specific survival was a sensitivity outcome. The investigators pooled data from 11 ARPI trials and more than 11,000 patients. Overall, there was a clear benefit of adding an ARPI on both OS and PFS, with hazard ratios of 0.66 and 0.51, respectively, representing a 13% and 21% absolute improvement at 5 years, respectively, with no clear difference by the class of agent. When stratifying the patients by age group, the effects of adding an ARPI on OS and PFS were slightly smaller in patients older than 75, than in those younger than 65, or aged between 65 and 75 years. Notably, in the trials assessing the use of abiraterone, we saw very little OS effects in the group of patients older than 75, however there was some benefit maintained in prostate-cancer specific survival, suggesting that other causes of death may be having an impact. The effects of the other ARPIs, or ‘lutamides' as I would call them, were similar across all three age subgroups on both OS and PFS. Therefore, the majority of patients with mHSPC benefit from the addition of ARPIs, and the benefits/risks of abiraterone and other ‘amides' must be considered in older patients.  Dr. Peter Hoskin: Thanks, Neeraj. Another great summary relevant to our day-to-day practice. Of course, there's ongoing collection of individual patient data from other key trials, which will allow robust comparison of ARPI doublet with triplet therapy (including docetaxel), guiding more personalized treatment.   Dr. Neeraj Agarwal: I agree with you, Peter, we need more data to help guide personalized treatment for patients with mHSPC and potentially guide de-escalation versus escalation strategies. Now, moving on to a different setting in prostate cancer, would you like to mention Abstract 17 titled, “Overall survival and quality of life with Lu-PSMA-617 plus enzalutamide versus enzalutamide alone in poor-risk, metastatic, castration-resistant prostate cancer in ENZA-p (ANZUP 1901),” presented by Dr. Louise Emmett? Dr. Peter Hoskin: Of course I will. So, ENZA-p was a multicenter, open-label, randomized, phase 2 trial conducted in Australia. It randomized 163 patients into adaptive doses (2 or 4 cycles) of Lu-PSMA-617 plus enzalutamide versus enzalutamide alone as first-line treatment in PSMA-PET-CT-positive, poor-risk, mCRPC. The interim analysis of ENZA-p with median follow-up 20 months showed improved PSA-progression-free survival with the addition of Lu-PSMA-617 to enzalutamide. Here, the investigators reported the secondary outcomes, overall survival, and health-related quality of life (HRQOL). After a median follow up of 34 months, overall survival was longer in the combination arm compared to the enzalutamide arm, with a median OS of 34 months compared to 26 months; with an HR of 0.55. Moreover, the combination improved both deterioration-free survival and health-related quality of life indicators for pain, fatigue, physical function, and overall health and quality of life compared to the control arm. Consistent with the primary analysis, the rPFS also favored the experimental arm with a median rPFS of 17 months compared to 14 months with a HR of 0.61. So, the addition of LuPSMA improved overall survival, and HRQOL in patients with high-risk mCRPC. Dr. Neeraj Agarwal: Thank you, Peter. Great summary, and promising results with Lu-177 and ARPI combination in first line treatment for mCRPC among patients who had two or more high risk features associated with early enzalutamide failure. Before we move on to bladder cancer, would you like to tell us about Abstract 15 titled, “World-wide oligometastatic prostate cancer (omPC) meta-analysis leveraging individual patient data (IPD) from randomized trials (WOLVERINE): An analysis from the X-MET collaboration,” presented by Dr. Chad Tang?  Dr. Peter Hoskin: Sure. So, with metastatic-directed therapy (MDT), we have a number of phase 2 studies making up the database, and the X-MET collaboration aimed to consolidate all randomized data on oligometastatic solid tumors. This abstract presented pooled individual patient data from all the published trials involving patients with oligometastatic prostate cancer who received MDT alongside standard of care (SOC) against SOC alone. The analysis included data from five trials, encompassing 472 patients with oligometastatic prostate cancer, and followed for a median of 41 months. Patients were randomly assigned in a 1:1 ratio to receive either MDT plus SOC or SOC alone. The addition of MDT significantly improved PFS. The median PFS was 32 months with MDT compared to 14.9 months with SOC alone, with an HR of 0.45. Subgroup analyses further confirmed the consistent benefits of MDT across different patient groups. Regardless of factors like castration status, receipt of prior primary treatment, stage, or number of metastases, MDT consistently improved PFS. In patients with mHSPC, MDT significantly delayed the time to castration resistance by nine months, extending it to a median of 72 months compared to 63 months in the SOC group with an HR of 0.58. In terms of OS, the addition of MDT improved the 48-month survival rate by 12%, with OS rates of 87% in the MDT+SOC group compared to 75% in the SOC alone group. Dr. Neeraj Agarwal: Thank you, Peter. These data demonstrate that adding MDT to systemic therapy significantly improves PFS, rPFS, and castration resistance-free survival, reinforcing its potential role in the treatment of oligometastatic prostate cancer. So, let's switch gears to bladder cancer and start with Abstract 658 reporting the OS analysis of the CheckMate-274 trial. Would you like to tell us about this abstract?  Dr. Peter Hoskin: Yes, sure, Neeraj. This was presented by Dr. Matt Milowsky, and it was additional efficacy outcomes, including overall survival, from the CheckMate-274 trial which evaluated adjuvant nivolumab versus placebo in patients with high-risk muscle-invasive bladder cancer after radical surgery. The phase 3 trial previously demonstrated a significant improvement in disease-free survival with nivolumab. With a median follow-up of 36.1 months, disease-free survival was longer with nivolumab compared to placebo across all patients with muscle-invasive bladder cancer, reducing the risk of disease recurrence or death by 37%. Among patients who had received prior neoadjuvant cisplatin-based chemotherapy, nivolumab reduced this risk by 42%, whilst in those who had not received chemotherapy, the risk was reduced by 31%. Overall survival also favored nivolumab over placebo, reducing the risk of death by 30% in all patients with muscle-invasive bladder cancer and by 52% in those with tumors expressing PD-L1 at 1% or higher. Among patients who had received prior neoadjuvant chemotherapy, nivolumab reduced the risk of death by 26%, whilst in those who had not received chemotherapy, the risk was reduced by 33%. Alongside this, the safety profile remained consistent with previous findings. Dr. Neeraj Agarwal: Thank you, Peter, for such a nice overview of this abstract. These results reinforce adjuvant nivolumab as a standard of care for high-risk muscle-invasive bladder cancer, offering the potential for a curative outcome for our patients. Dr. Peter Hoskin: I agree with you Neeraj. Perhaps you would like to mention Abstract 659 titled, “Additional efficacy and safety outcomes and an exploratory analysis of the impact of pathological complete response (pCR) on long-term outcomes from NIAGARA.” Dr. Neeraj Agarwal: Of course. Dr. Galsky presented additional outcomes from the phase 3 NIAGARA study, which evaluated perioperative durvalumab combined with neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer. The study previously demonstrated a significant improvement in event-free survival and overall survival with durvalumab compared to chemotherapy alone, with a manageable safety profile and no negative impact on the ability to undergo radical cystectomy. Among the 1,063 randomized patients, those who received durvalumab had a 33% reduction in the risk of developing distant metastases or death and a 31% reduction in the risk of dying from bladder cancer compared to those who received chemotherapy alone. More patients who received durvalumab achieved a pathological complete response at the time of surgery with 37% compared to 28% in the chemotherapy-alone group. Patients who achieved a pathological complete response had better event-free survival and overall survival compared to those who did not. In both groups, durvalumab provided additional survival benefits, reducing the risk of disease progression or death by 42% and the risk of death by 28% in patients with a pathological complete response, while in those patients without a pathological complete response, the risk of disease progression or death was reduced by 23% and the risk of death by 16% when durvalumab was added to the chemotherapy. Immune-mediated adverse events occurred in 21% of patients in the durvalumab group compared to 3% in the chemotherapy-alone group, with grade 3 or higher events occurring in 3% compared to 0.2%. The most common immune-related adverse events included hypothyroidism in 10% of patients treated with durvalumab compared to 1% in the chemotherapy-alone group, and hyperthyroidism in 3% versus 0.8%. At the time of the data cutoff, these adverse events had resolved in 41% of affected patients in the durvalumab group and 44% in the chemotherapy-alone group. Dr. Peter Hoskin: Thank you, Neeraj, for the great summary. These findings further support the role of perioperative durvalumab as a potential standard of care for patients with muscle-invasive bladder cancer. Dr. Neeraj Agarwal: I concur with your thoughts, Peter. Before wrapping up the bladder cancer section, would you like to mention Abstract 664 reporting updated results from the EV-302 trial, which evaluated enfortumab vedotin in combination with pembrolizumab compared to chemotherapy as first-line treatment for patients with previously untreated locally advanced or metastatic urothelial carcinoma? Dr. Peter Hoskin: Yes, of course. Dr. Tom Powles presented updated findings from the EV-302 study, and in this abstract presented 12 months of additional follow-up for EV-302 (>2 y of median follow-up) and an exploratory analysis of patients with confirmed complete response (cCR). The study had a median follow-up of 29.1 months and previously demonstrated significant improvements in progression-free survival and overall survival with enfortumab vedotin and pembrolizumab. This is now the standard of care in global treatment guidelines. Among the 886 randomized patients, enfortumab vedotin and pembrolizumab reduced the risk of disease progression or death by 52% and the risk of death by 49% compared to chemotherapy. The survival benefit was consistent regardless of cisplatin eligibility or the presence of liver metastases. The confirmed objective response rate was higher with enfortumab vedotin and pembrolizumab at 67.5% compared to 44.2% with chemotherapy. The median duration of response was 23.3 months with enfortumab vedotin and pembrolizumab compared to 7.0 months with chemotherapy. A complete response was achieved in 30.4% of patients in the enfortumab vedotin and pembrolizumab group compared to 14.5% in the chemotherapy group, with the median duration of complete response not yet reached in the enfortumab vedotin and pembrolizumab group compared to 15.2 months in the chemotherapy group. Severe treatment-related adverse events occurred in 57.3% of patients treated with enfortumab vedotin and pembrolizumab compared to 69.5% in the chemotherapy group, while in patients who achieved a complete response, severe adverse events occurred in 61.7% of those treated with enfortumab vedotin and pembrolizumab compared to 71.9% with chemotherapy. Treatment-related deaths were reported in 1.1% of patients treated with enfortumab vedotin and pembrolizumab compared to 0.9% with chemotherapy, with no treatment-related deaths occurring in those who achieved a complete response. These findings clearly confirm the durable efficacy of enfortumab vedotin and pembrolizumab, reinforcing its role as the standard of care for the first-line treatment of patients with locally advanced or metastatic urothelial carcinoma, and no new safety concerns have been identified. Dr. Neeraj Agarwal: Thank you for this great summary. Moving on to kidney cancer, let's talk about Abstract 439 titled, “Nivolumab plus cabozantinib (N+C) vs sunitinib (S) for previously untreated advanced renal cell carcinoma (aRCC): Final follow-up results from the CheckMate-9ER trial.” Dr. Peter Hoskin: Sure. Dr. Motzer presented the final results from the phase 3 CheckMate-9ER trial, which compared the combination of cabozantinib and nivolumab against sunitinib in previously untreated advanced renal cell carcinoma. The data after more than five years follow-up show that the combination therapy provided sustained superior efficacy compared to sunitinib. In terms of overall survival, we see an 11-month improvement in median OS, 46.5 months for the cabo-nivo versus 35.5 months for sunitinib and a 42% reduction in the risk of disease progression or death, with median progression-free survival nearly doubling – that's 16.4 months in the combination group and 8.3 months with sunitinib. Importantly, the safety profile was consistent with the known safety profiles of the individual medicines, with no new safety concerns identified. Dr. Neeraj Agarwal: Great summary, Peter. These data further support the efficacy of cabo-nivo combination therapy in advanced renal cell carcinoma, which is showing a 11-month difference in overall survival. Dr. Peter Hoskin: Neeraj, before wrapping up this podcast, would you like to tell us about Abstract 618? This is titled “Prospective COTRIMS (Cologne trial of retroperitoneal lymphadenectomy in metastatic seminoma) trial: Final results.” Dr. Neeraj Agarwal: Sure, Peter. I would be delighted to. Dr Heidenrich from the University of Cologne in Germany presented the COTRIMS data evaluating retroperitoneal LN dissection in patients with clinical stage 2A/B seminomas. Seminomas are classified as 2A or B when the disease spreads to the retroperitoneal lymph nodes of up to 2 cm (CS IIA) or of more than 2 cm to up to 5 cm (CS 2B) in maximum diameter, respectively. They account for 10-15% of seminomas and they are usually treated with radiation and chemotherapy. However, radiation and chemo can be associated with long-term toxicities such as cardiovascular toxicities, diabetes, solid cancers, leukemia, particularly for younger patients. From this standpoint, Dr Heidenrich and colleagues evaluated unilateral, modified template, nerve-sparing retroperitoneal lymph node dissection as a less toxic alternative compared to chemo and radiation. They included 34 patients with negative AFP, beta-HCG, and clinical stage 2A/B seminomas. At a median follow-up of 43.2 months, the trial demonstrated great outcomes: a 99.3% treatment-free survival rate and 100% overall survival, with only four relapses. Antegrade ejaculation was preserved in 88% of patients, and severe complications such as grade 3 and 4 were observed in 12% of patients. Pathological analysis revealed metastatic seminoma in 85% of cases, with miR371 being true positive in 23 out of 24 cases and true negative in 100% of cases. It appears to be a valid biomarker for predicting the presence of lymph node metastases. These findings highlight retroperitoneal lymph node dissection is feasible; it has low morbidity, and excellent oncologic outcomes, avoiding overtreatment in 80% of patients and sparing unnecessary chemotherapy or radiotherapy in 10-15% of cases. Dr. Peter Hoskin: Great summary and important data on retroperitoneal lymphadenectomy in metastatic seminoma. These findings will help shape clinical practice. Any final remarks before we conclude today's podcast? Dr. Neeraj Agarwal: Before wrapping up this podcast, I would like to say that we have reviewed several abstracts addressing prostate, bladder, kidney cancers, and seminoma, which are impacting our medical practices now and in the near future. Peter, thank you for sharing your insights with us today. These updates are undoubtedly exciting for the entire GU oncology community, and we greatly appreciate your valuable contribution to the discussion and your leadership of the conference. Many thanks. Dr. Peter Hoskin: Thank you, Neeraj. Thank you for the opportunity to share this information more widely. I'm aware that whilst we have nearly 6,000 delegates, there are many other tens of thousands of colleagues around the world who need to have access to this information. And it was a great privilege to chair this ASCO GU25. So, thank you once again, Neeraj, for this opportunity to share more of this information that we discussed over those few days. Dr. Neeraj Agarwal: Thank you, Peter. And thank you to our listeners for joining us today. You will find links to the abstracts discussed today on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.  Find out more about today's speakers:   Dr. Neeraj Agarwal    @neerajaiims    Dr. Peter Hoskin Follow ASCO on social media:      @ASCO on Twitter      ASCO on Bluesky  ASCO on Facebook      ASCO on LinkedIn      Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas Dr. Peter Hoskin: Research Funding (Institution): Varian Medical Systems, Astellas Pharma, Bayer, Roche, Pfizer, Elekta, Bristol Myers  

This week James and Jeff delve into one (...of the many) subgroup analyses of the DREAM study. What is better surgery or Physiotherapy for meniscal tears?How can we predict which patients will do well in each group? Why does Jeff hate the world of research?

LATE BREAKING CLINICAL SCIENCE: Benefits of Dynamx Bioadaptor Versus DES in Patients With Dyslipidemia: Subgroup Analysis Results from the BIOADAPTOR RCT

Why you should listenLearn how Google Ads work specifically for tech and consulting businesses, including different types of campaigns and their effectiveness.Discover why Google remains a dominant player in digital advertising and how to leverage its strengths even in a competitive landscape.Gain insights into the power of retargeting ads and how to create effective campaigns that resonate with your audience.Are you struggling to generate leads beyond referrals and partnerships? In this episode, we tackle this common challenge with expert insights from John Horn, CEO of the StubGroup. With over 11 years of experience in digital marketing, John reveals how Google Ads can be a game-changer for tech consultants and businesses seeking to attract more clients. He discusses the mechanics of Google Ads, the platform's enduring relevance despite emerging AI competitors, and effective strategies for retargeting ads to engage potential customers who have already shown interest in your services.About John HornJohn Horn is the CEO of StubGroup, a digital advertising agency and a premier Google ad agency. Subgroup has helped over 2000 clients, across 15k campaigns, with their paid ads and suspension issues. They have generated over half a billion dollars in revenue for their clients across many different verticals including ecommerce, lead generation, B2B, B2C, local services, and more.John has also taught digital advertising to over 100,000 students via online courses and the videos he produces through StubGroup's YouTube channel have received millions of views. When he's not marketing, John loves spending time with his wife and two little boys and exploring the Texas countryside he calls home.Resources and Linksstubgroup.comJohn's LinkedIn profileStubGroup Youtube channel: @StubgroupPrevious episode: 585 - The LinkedIn Assistant That Helps Users Save Time and Make Money with Joe ApfelbaumCheck out more episodes of The Paul Higgins ShowSubscribe to our YouTube channel: @PaulHigginsMentoringThe Tech Consultant's RoadmapJoin our newsletterJoin the Tech CollectiveSuggested resources

In this episode, we dive into the hottest updates in myeloma and amyloidosis at ASH 2024 annual meeting with Dr. Rakesh Popat. Here are the abstracts we discussed: 1. AQUILA Trial in High-Risk SMMOverview of the AQUILA trial testing single-agent daratumumab for high-risk smoldering multiple myeloma (HR-SMM) versus active monitoring. Discussion on patient characteristics, primary endpoints, and results showing significant progression-free survival (PFS) benefit with Dara. Insights into modes of progression, adequacy of active surveillance, and post-protocol therapy in control arm. Read the abstract. Read the simultaneous publication at NEJM. 2. Anito-Cel: New BCMA CAR T Therapy Early data from the iMMagine-1 trial showing strong efficacy and a promising safety profile for Anito-Cel, a novel BCMA CAR T. Discussion of its potential to rival cilta-cel while avoiding neurotoxicity concerns. Read the abstract.3. CARTITUDE-4 Update Updates on MRD-negativity rates and survival outcomes for cilta-cel in relapsed myeloma, with significant benefits over standard care. Read the abstract.4. ANDROMEDA OS Data in AL Amyloidosis Long-term data showing an overall survival (OS) benefit of Dara-VCd over VCd in AL amyloidosis. Insights into cardiac responses and crossover impact. Read the abstract.5. OPTIMUM Trial in Ultra-High-Risk NDMMFive-year follow-up of a tailored approach for ultra-high-risk newly diagnosed myeloma patients with continuous therapy incorporating multiple active agents. Subgroup outcomes highlighting both challenges and exceptional results. Read the abstract6. GMMG-HD7 Trial PFS Update Phase 3 trial results on Isa-VRD vs. VRD induction and risk-adapted tandem ASCT. Discussion on the role of CD38 in maintenance therapy. Read the abstract Read the simultaneous publication at JCO7. Exciting New Drugs Review of three innovative therapies: inobrodib, a BCMA-CD38 trispecific antibody, and cevostamab, a FcRH5-targeted bispecific antibody. Expert insights into their efficacy and potential to reshape myeloma care. Read the abstract

Episode 112: Grab the Ultimate Ad Script right HERE - https://join.digitaltrailblazer.com/ultimate-ad-scriptGoogle ads work for a lot of businesses, but do they actually work for selling online courses, coaching programs, or agency services?At first, it seems like you should be able to find very high-intent buyers if you target the right keywords… if someone is searching for “best fitness coach”, you would think that running ads for that keyword would give you “ready-to-buy” leads, right?The answer is more complicated than one might think.In this episode, Google Ads expert John Horn breaks down the pros and cons of Google ads for coaches and course creators and explains when it might make sense and when it doesn't. He also gives us a bunch of tips on how to make different types of paid ads work for online businesses.About John Horn: John Horn is the CEO of StubGroup, a digital advertising agency and a premier Google ad agency. Subgroup has helped over 2000 clients, across 15k campaigns, with their paid ads and suspension issues. They have generated over half a billion dollars in revenue for their clients across many different verticals including ecommerce, lead generation, B2B, B2C, local services, and more.John has also taught digital advertising to over 100,000 students via online courses and the videos he produces through StubGroup's YouTube channel have received millions of views. When he's not marketing, John loves spending time with his wife and two little boys and exploring the Texas countryside he calls home.Grab John's Free Resources Here: https://stubgroup.com/free/Connect with John: Website: https://stubgroup.com/ LinkedIn: https://www.linkedin.com/in/johnjhorn1/ Youtube: https://www.youtube.com/@Stubgroup Facebook: https://www.facebook.com/StubGroup/ Instagram: https://www.instagram.com/stubgroupadvertising/ TikTok: https://www.tiktok.com/@stubgroup Twitter: https://twitter.com/stubgroup LinkedIn: https://www.linkedin.com/company/stub-group/Grab our Ultimate Ad Script for Coaches, Agencies, and Course Creators.Learn the exact 5-step script we teach our clients that allows them to generate targeted, high-quality leads at ultra-low cost, so you can land paying customers and clients without breaking the bank on ad spend.Grab the Ultimate Ad Script right HERE - https://join.digitaltrailblazer.com/ultimate-ad-script✅ Connect With Us:Website - https://DigitalTrailblazer.comFacebook - https://www.facebook.com/digitaltrailblazer/TikTok: https://www.tiktok.com/@digitaltrailblazerTwitter: https://twitter.com/DgtlTrailblazerInstagram: https://www.instagram.com/DigitalTrailblazer

Instead of grouping together people with autism based on traditional severity scores, what if groupings were done based on functional outcome? Would this help better understand the broad spectrum of autism and why some people with autism are so different than others? Researchers at the University of Minnesota led by Kyle Sterrett, together with UCLA … Continue reading "Profound Autism: The first meaningful autism subgroup"

Lancet 1982;320:1173-1180Background: The first coronary artery bypass graft surgery (CABG) was performed in 1964 and by the 1970's it was commonly used for relief of angina. However, whether it improved survival was unknown. The European Coronary Surgery Study (ECSS) sought to test the hypothesis that CABG compared to medical therapy improved survival at 5 years.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Note to readers: Several preliminary reports of ECSS results were published at earlier time points (2 and 3-5 years). We are reporting the 5-year results since this was the prespecified hypothesis the investigators sought to test.Patients: Men under 65 years of age with angina pectoris of more than 3 months duration, a left ventricular ejection fraction >50%, and angiographic obstruction of >/=50% in at least 2 major coronary vessels with at least 1 vessel suitable for grafting. Patients with severe angina that could not be controlled with medical therapy were excluded.Baseline characteristics: No information is provided in the main paper on the number or characteristics of individuals screened to enrolled. There were 768 patients enrolled in the study. They were recruited from September, 1973 to March, 1976. The average age of patients was 50 years and the left ventricular ejection fraction was 65%. Approximately, 46% had a previous heart attack, 43% smoked, 35% had a high cholesterol, 15% had hypertension and 6% had diabetes. In terms of coronary anatomy, 53% had 3-vessel disease, 40% had 2-vessel disease, and 7% had left main disease.Procedures: Patients were randomly assigned to receive medical or surgical treatment. Medical measures varied based on location. The authors reported that strict standardization was not felt to be practical or necessary. Surgical treatment was either with saphenous-vein graft or internal mammary artery and was performed as soon as possible following randomization. The average time from randomization to surgery was approximately 4 months.Follow-up evaluations were performed 6 months after randomization and annually thereafter. Graft angiography was planned at 6 and 12 months after operation.Endpoints: The primary endpoint was all-cause death. The prespecified minimum follow-up time, set at the start of the trial, for all patients was 5 years. At the time of this report, some patients had been followed up to 8 years. A strict hypothesis was not tested (i.e., CABG would reduce death by X% compared to medical therapy). The primary analysis was a traditional intention to treat analysis and medical patients who crossed over to surgery and surgical patients who died prior to receiving surgery or refused surgery after randomization were retained within their original groups.Results: There were 767 patients included in the final analysis; 373 patients in the medical group and 394 in the surgical group (1 patient was lost from the surgical group immediately following randomization and was not counted in the group). At 5 years, 90 patients (24%) of the medical group had crossed over to surgery and 26 (7%) of the surgical patients were not operated on. An average of 1.9 grafts per patient were performed in the 2-vessel disease subgroup and 2.4 grafts per patient in the 3-vessel disease subgroup. The graft patency rate was 90% within 9 months and 77% between 9 and 18 months.Compared to medical therapy, surgery significantly reduced death at 5 years by 53% (7.6% vs 16.4%; p=0.00025). Operative (in-hospital) mortality was 3.6% for a total of 494 operations and 7.7% for 26 reoperations. Seven of 27 prespecified variables recorded at the time of randomization were found to be associated with significant treatment effect heterogeneity. They included: (i) extent of disease; (ii) location of lesion(s) in the proximal third of the left anterior descending artery (proximal LAD); (iii) resting ECG suggestive of previous possible or probable myocardial infarction and/or with other specified abnormalities (iv) ischemic ST-segment response predominantly in lead V5 during maximum level of a multistage symptom/sign-limited bicycle exercise test; (v) history of peripheral arterial disease; (vi) age; and (vii) mode of treatment.Subgroup analysis on the basis of coronary anatomy supported a significant advantage of surgery for patients with left main disease (14.3% vs 32.1%; p=0.11) and 3-vessel disease (6% vs 17.6%; p=0.003) but not in 2-vessel disease (8.8% vs 11.8%; p>0.20). The left main subgroup could have had 2- or 3-vessel disease and the p-value was insignificant due to the small sample size.Surgery significantly reduced death in patients with proximal LAD disease (7.3% vs 18%; p=0.0004) but not in those without it (6.7% vs 7.9%; p>0.20). In the subset of patients with 2-vessel disease and without proximal LAD disease, surgery caused a numerical increase in death at 5 years, attributed to operative mortality.Surgery significantly reduced death in patients with >/= 1.5mm exertional ST depression on bicycle testing (8.3% vs 21%; p=0.003) but not in those without it (5.1% vs 9.7%; p>0.20).Angina and exercise performance were significantly improved in the surgery group compared to medicine. Conclusions: Compared to medical therapy, bypass surgery using internal mammary arteries and saphenous vein grafts significantly reduced mortality at 5 years in men under 65 years of age with normal left ventricular function. Approximately 11 men would need to be treated with CABG to prevent 1 death. This represents a large benefit for bypass surgery in well-selected patients at the time the study was undertaken. Contemporary caveats to this interpretation include improvements in medical therapy since the publication of ECSS mainly involving aspirin and cholesterol lowering drugs for patients with CAD as well as an improvement in the general management of conditions like hypertension and diabetes. Also, smoking rates have significantly declined at the population level.Despite the impressive benefit of bypass surgery seen in this study, important treatment effect heterogeneity was identified for certain lower risk patient groups including those with 2-vessel disease, absence of proximal LAD disease, and minimal ST depression on symptom limited bicycle testing. Theoretically, such patients would be expected to benefit from bypass surgery even less today given the improvements in medical therapy mentioned above.Finally, it is worth pointing out the difference in treatment effects seen in this study compared to the Veterans Administration Cooperative Study that we reviewed earlier this week, which was a negative trial. In the Veterans Administration Cooperative Study, coronary bypass was performed primarily with saphenous vein grafting whereas ECSS used internal mammary arteries and saphenous vein grafts. Internal mammary arteries are superior conduits compared to vein grafts. They have improved long-term patency rates, which is attributed to their striking resistance to the development of atherosclerosis. Furthermore, they are used almost exclusively on the LAD, which is the most important vessel.In conclusion, ECSS demonstrated that CABG surgery dramatically reduced death at 5 years compared to medical treatment; however, we should be aware of the caveats mentioned above and appreciate that the trial was limited to highly selected male patients under the age of 65.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

At the 2024 European Hematology Association (EHA) Congress, CancerNetwork® spoke with a variety of experts in the hematologic oncology space about optimizing outcomes across different patient populations and subgroups based on updated research they presented at the meeting.  Manali Kamdar, MD, an associate professor of medicine-hematology and clinical director of Lymphoma Services at the University of Colorado Anschutz Medical Campus, in Colorado, spoke about data from the phase 1 TRANSCEND NHL 001 trial (NCT02631044) supporting the use of lisocabtagene maraleucel (liso-cel; Breyanzi) in earlier lines of therapy for patients with relapsed/refractory mantle cell lymphoma (MCL).1  Specifically, Kamdar highlighted how research should continue to focus on the potential utility of liso-cel in MCL subgroups such as those with TP53 mutations or blastoid morphology. Additionally, she stated that liso-cel may need to be further tested in earlier lines of therapy for patients with diffuse large B-cell lymphoma, including those with double-hit lymphoma. Michael R. Grunwald, MD, chief of the Leukemia Division and director of the Transplantation and Cellular Therapy Program at Atrium Health's Levine Cancer Institute, in North Carolina, discussed findings from the Prospective Observational Study of Patients With Polycythemia Vera (PV) in US Clinical Practices Trial (REVEAL) exploring risk factors for disease progression in patients with polycythemia vera (PV).2 According to Grunwald, a history of thromboembolic events, elevated white blood cell counts, and higher variant allele frequencies may contribute to a patient's likelihood of experiencing progression to myelofibrosis or acute myeloid leukemia (AML). Additionally, he highlighted ongoing research into the potential molecular factors that may prognosticate disease transformation in PV among a small cohort of patients enrolled on the REVEAL trial.3 Harry P. Erba, MD, PhD, a professor of medicine in the Division of Hematologic Malignancies and Cellular Therapy and the director of the Leukemia Program and Phase I Development in Hematologic Malignancies at Duke Cancer Institute, in North Carolina, discussed the clinical implications of data from the phase 3 QuANTUM-First study (NCT02668653).4  Specifically, findings demonstrated that continuation therapy with quizartinib (Vanflyta) elicited a more pronounced survival benefit vs placebo in patients with newly diagnosed FLT3-ITD–positive AML who did not undergo allogeneic hematopoietic stem cell transplant (allo-HSCT). However, Erba noted that survival outcomes were not significantly different in the quizartinib and placebo arms among patients who received allo-HSCT. References 1.        Palomba ML, Siddiqi T, Gordon LI, et al. Subgroup analyses in patients with R/R MCL treated with lisocabtagene maraleucel by prior lines of therapy and response to Bruton tyrosine kinase inhibitor from the TRANSCEND NHL 001 MCL cohort. Presented at the European Hematology Association (EHA) 2024 Congress; Madrid, Spain; June 13-16, 2024. P1126. 2.        Grunwald M, Zwicker J, Gerds A, et al. A real-world evaluation of risk factors for disease progression in patients with polycythemia vera (PV) enrolled in REVEAL. Presented at the 2024 European Hematology Association (EHA) Congress; June 13-16, 2024; Madrid, Spain. Abstract P1047. 3.        Crowgey E, Timmers C, Xue Z, et al. Analysis of molecular mechanisms and predictive biomarkers of disease transformation in polycythemia vera. Presented at the 2024 European Hematology Association (EHA) Congress; June 13-16, 2024; Madrid, Spain. Abstract S217. 4.        Sekeres MA, Erba H, Montesinos P, et al. QuANTUM-First: efficacy in newly diagnosed patients with FMS-like tyrosine kinase 3-internal tandem duplication–positive (FLT3-ITD+) acute myeloid leukemia (AML) who received continuation therapy. Presented at the 2024 European Hematology Association (EHA) Congress; June 13-16, 2024; Madrid, Spain. Abstract S142.

N Engl J Med 2013;369:999-1010Background: Adding P2Y12 inhibitors to aspirin improves outcomes in patients with acute coronary syndrome. Yet, debate persisted regarding the optimal timing for administering these drugs in patients undergoing percutaneous coronary intervention (PCI). The ATLANTIC trial showed that pre-hospital administration of ticagrelor did not improve outcomes compared to in-hospital administration, in patients with ST elevation myocardial infarction.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.The ACCOAST trial sought to test the hypothesis that administering the P2Y12 inhibitor, prasugrel, 2-48 hours before angiography in non-ST elevation myocardial infarction patients is superior to administering it during PCI.Patients: Patients were enrolled if they had non-ST elevation myocardial infarction. Patients were scheduled to undergo angiography with possible PCI within 2-48 hours after randomization. Patients were excluded if they had cardiogenic shock, refractory ventricular arrhythmias, prior hemorrhagic or ischemic stroke or TIA, history of intracranial neoplasms, history of intracranial AV malformations or aneurysm, surgery within 4 weeks, active bleeding or history of bleeding diathesis or had high risk of bleeding based on the judgement of the investigator.Baseline characteristics: The average age of patients was 64 years with 72% being men. The average weight was 82 kg. About 20% had diabetes, 45% had hyperlipidemia, 62% had hypertension and 33% were current smokers. Creatinine clearance was ≤ 30 ml/min in 3% of the patients and GRACE score was < 140 in 77% of them. Beta-blockers were given in 84% of the patients, statins in 90%, angiotensin-receptor blockers in 13% and ACE inhibitors in 70%.After randomization, 68.7% of the patients underwent PCI while 25.1% were treated medically. CABG within 7 days was performed in 6.2% of the patients.Procedures: Patients were randomized 1:1 to receive pretreatment with prasugrel or matching placebo (control group). Those in the pretreatment group received a 30 mg loading dose of prasugrel before coronary angiography with an additional 30 mg if angiography confirmed the need for PCI. Patients in the control group received placebo before coronary angiography and a 60 mg loading dose of prasugrel in patients undergoing PCI. Only the initial 30 mg loading dose of prasugrel or placebo were administered, if a decision, after coronary angiography, was made to pursue CABG or medical therapy.Endpoints: The primary efficacy end point was a composite endpoint of death from cardiovascular causes, myocardial infarction, stroke, urgent revascularization, or the need for rescue therapy with glycoprotein IIb/IIIa inhibitors. Follow up for the primary endpoint was 7 days post randomization. Secondary endpoints included death from any cause, stent thrombosis and a composite endpoint of death from cardiovascular causes, myocardial infarction, or stroke.Safety end points were major or minor bleeding according to Thrombolysis in Myocardial Infarction (TIMI) criteria.Statistical analysis was performed on the intention-to-treat principle. To achieve 80% power with two-sided alpha of 0.05 for detecting 24% relative risk reduction in the pretreatment compared to the control group, 400 patients with the primary outcome and approximately 4,100 enrolled patients would be needed.Results: The trial randomized 2,037 patients to the pre-treatment group and 1,996 to the control group. The median time from the initial loading dose to PCI was 4.3 hours.The incidence of the composite primary end point was similar between both treatment groups (10.0% in the pre-treatment group vs 9.8% in the control group, HR: 1.02, 95% CI: 0.84 – 1.25; p= 0.81). There was no significant difference between both treatment groups in any of the components of the primary end point, death from any cause, or stent thrombosis. Results were similar for patients who underwent PCI (about two thirds of study participants).There were more major bleeding events at 7 days in the pretreatment group (2.6% vs 1.4%, HR: 1.90, 95%: 1.19 – 3.02; p= 0.006). Major bleeding events not related to CABG were also higher in the pre-treatment group (1.3% vs 0.5%; p= 0.003). In the PCI cohort, 12 patients in the pre-treatment group had life-threatening bleeding compared to 2 in the control group. Most bleedings in this cohort were access site bleeding, pericardial bleeding and retroperitoneal bleeding.Subgroup analysis for the primary efficacy endpoint did not identify any subgroup who would benefit from pre-treatment with prasugrel.Conclusion: In patients with non-ST elevation myocardial infarction undergoing coronary angiography within 48 hours of admission, pre-treatment with prasugrel did not improve ischemic events and resulted in more major bleeding.The results of this trial led to the recommendation that prasugrel should be used after coronary anatomy is defined and PCI is chosen as the treatment strategy. This approach will reduce the risk of bleeding complications without increasing the risk of ischemic events.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

JAMA. 2013;309(12):1241-1250Background Case reports as early as the 1950s suggested chelation of lead might reduce angina. The popularity of chelation accelerated around the turn of the century. Small underpowered trials of chelation were inconclusive. Mainstream medicine considered chelation unproven and potentially hazardous.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.Chelation with disodium EDTA binds divalent and some trivalent cations, including calcium, magnesium, lead, cadmium, zinc, iron, aluminum, and copper, which facilitates their urinary excretion. High dose vitamins are often co-administered with chelation.The NIH-funded Trial to Assess Chelation Therapy (TACT) trial was conducted to respond to the public health problem posed by EDTA chelation therapy: namely, that large numbers of patients could be exposed to undefined risks for unproven benefits. TACT was a double-blind placebo-controlled 2x2 factorial randomized trial enrolling 1708 patients to test chelation therapy.Patients Eligibility for TACT required patients be older than 50 years, have a creatinine of < 2 mg/dl, and have survived a previous myocardial infarction. Exclusion criteria included platelet count less than 100 000/μL, abnormal liver function, BP > 160/100 mm Hg, past intolerance to the chelation or vitamin components, chelation therapy within 5 years, coronary or carotid revascularization planned or having taken place within 6 months, cigarette smoking within 3 months, active heart failure or heart failure hospitalization within 6 months, or inability to tolerate 500-mL infusions weekly. Enrollment began in 2003 and follow-up continued until 2011. There were 134 sites; 60% of which were established chelation centers.Baseline Characteristics The median age of patients was 65 years, 18% were women and the median body mass index was 30. More than 90% of patients had had either percutaneous coronary intervention or coronary bypass surgery. Approximately 31% of patients had diabetes. Use of guideline directed medications was typical of a well-treated population of post-MI patients. Procedures The active 10-component chelation solution consisted of up to 3 g of disodium EDTA; 7 g of ascorbic acid; 2 g of magnesium chloride; 100 mg of procaine; 2500 U of unfractionated heparin; 2 mEq of potassium chloride; 840 mg of sodium bicarbonate; 250 mg of pantothenic acid; 100 mg of thiamine; 100 mg of pyridoxine; and sterile water to make up 500 mL of solution. The identical-appearing placebo solution consisted of 500 mL of normal saline and 1.2% dextrose (2.5 g total).The chelation or placebo infusions were administered through a peripheral intravenous line, weekly for the first 30 infusions, followed by an additional 10 infusions 2 to 8 weeks apart. Patient also received an oral vitamin-mineral regimen vs an oral placebo. In this review, we focus on the intention-to-treat comparison of EDTA chelation vs placebo.Endpoints The primary endpoint was a composite of death, reinfarction, stroke, coronary revascularization, or hospitalization for angina.TACT trialists had planned to enroll 2300 patients over three years with a follow-up of one year. Enrollment was slow, and with permission from the data safety monitoring board (DSMB) enrollment was decreased to 1700 patients and follow-up was extended. The resultant power was 85% to detect a 25% reduction in the primary endpoint assuming a 2.5% per year event rate in the placebo arm.Over the course of the trial, the DSMB requested 11 interim analyses of the data. Because of the increased monitoring, the level of statistical significance required for the primary endpoint was enhanced to a P value of less than 0.036.Results After a median follow-up of 55 months, a primary end point occurred in 222 (26%) of the chelation group and 261 (30%) of the placebo group (hazard ratio [HR]: 0.82 [95% CI: 0.69-0.99]; p= .035). There was no effect on total mortality (10% vs 11%, HR: 0.93, 95% CI: 0.70-1.25; p= 0.64). Myocardial infarction and coronary revascularization favored chelation (6% vs 8% and 15% vs 18%, respectively), however this did not reach statistical significance for either endpoints.Subgroup analysis revealed a potentially important heterogenous treatment effect. In patients with diabetes (about a third of patients) there was an approximate 40% reduction in the primary endpoint (HR: 0.61, 95% CI: 0.45-0.83; p= 0.002).There were no significant differences in adverse effects between the two groups.The trialists did sensitivity analyses centering on patients who withdrew from the trial or were lost to follow-up. The comparison of the 2 groups remained significant even if the percentage of events among withdrawn/lost patients in the active group was 25% higher than in the placebo group.Conclusions The results of the TACT trial surprised the cardiology community. Prior beliefs were pessimistic because heavy metals was not a proven causal factor in atherosclerosis. What's more, the majority of patients were enrolled from non-traditional medical centers.Yet the effect size was both clinically important and statistically significant. The effect size in the diabetes subgroup, which was pre-specified, was even larger and more robust statistically than the general results. In fact, there was essentially no signal of benefit from chelation in non-diabetic patients. If this was confirmed, it would be a major finding both therapeutically and scientifically, as it would have discovered heavy metal exposure as an important cause of atherosclerosis.The Journal of the American Medical Association published the manuscript along with an explanatory letter from the editors, and an accompanying editorial from Dr. Steve Nissen, which challenged the internal validity of the trial.The results of TACT did not lead to widespread adoption of chelation, but it did lead primary investigator Gervasio Lamas to seek (and obtain) funding for a TACT 2 trial to study chelation in patients with diabetes. Experts often refer to subgroup findings as “hypothesis-generating” and so it was with the TACT 1 and TACT 2 trials.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

N Engl J Med 2010;363:930-942Background By 2010, dual antiplatelet therapy had been established as beneficial during and after percutaneous coronary intervention for acute coronary syndromes. Optimal dosing however remained unknown. This included the best loading dose of clopidogrel and optimal dose of aspirin.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.The Clopidogrel and Aspirin Optimal Dose Usage to Reduce Recurrent Events−Seventh Organization to Assess Strategies in Ischemic Syndromes (CURRENT–OASIS 7) trial was designed to determine whether a doubling of the loading and initial maintenance doses of clopidogrel is superior to the standard-dose regimen and whether higher-dose aspirin (300 to 325 mg daily) is superior to lower-dose aspirin (75 to 100 mg daily) in patients with acute coronary syndromes referred for an early invasive strategy.Patients Adult patients who presented with a non-ST-segment elevation acute coronary syndrome (ACS) or an ST-segment elevation myocardial infarction. Patients had to have had coronary angiography with a plan to perform PCI within 72 hours. Major exclusion criteria were an increased risk of bleeding or active bleeding and a known allergy to clopidogrel or aspirin. Baseline Characteristics Nearly all patients had angiography. About 68% had PCI and 32% did not have PCI due to lack of significant (≤70%) stenosis. About a quarter of patients had coronary-artery bypass surgery. The average age of patients was 61 years; 27% female sex, and 70% had a diagnosis of unstable angina or NSTEMI. The median time to randomization in patients with unstable angina/NSTEMI was 3.4 days vs 0.6 days in patients with STEMI. About 60% of patients were white, and 22% were Asian. The co-existing cardiac risk factors, such as smoking, hypertension, diabetes and previous MI were similar in all the trial arms, and typical of most trials at the time.Procedures The CURRENT-OASIS 7 trial had 2x2 factorial design. First, comparing in a double-blind fashion, a double dose vs standard dose clopidogrel regimen. In the second component, patients were randomly assigned in an open-labeled fashion to higher- or lower-dose aspirin.Immediately after randomization and before coronary angiography, patients randomly assigned to double-dose clopidogrel received a loading dose of 600 mg on day 1, followed by 150 mg once daily on days 2 through 7. Patients assigned to standard-dose clopidogrel received a 300-mg loading dose on day 1 before angiography, followed by 75 mg once daily on days 2 through 7. On days 8 through 30, both the double-dose and standard-dose groups received 75 mg of clopidogrel once daily.Patients randomly assigned to lower-dose aspirin received 75 to 100 mg daily on days 2 through 30, and those randomly assigned to higher-dose aspirin received 300 to 325 mg daily on days 2 through 30. An initial loading dose of aspirin 300 mg was used in both arms on day 1. Other therapies, such as anti-thrombotics were left to the discretion of the treating doctors. Endpoints The primary endpoint was cardiovascular death, myocardial infarction, or stroke at 30 days. The sample-size calculation estimated an event rate of 11% at 30 days with standard-dose clopidogrel or lower-dose aspirin. That would have led to 14,000 patients to have 90% power to detect a 16% reduction in the primary endpoint. Lower-than expected event rates required an increase in sample size to 25,000 patients. This allowed for an 80% power to detect a 16% reduction in the primary endpoint.Results  A primary outcome event occurred in 4.2% of patients in the double-dose clopidogrel group at 30 days, as compared with 4.4% in the standard-dose group (hazard ratio, 0.94, 95% confidence interval [CI], 0.83 to 1.06; P=0.30). The rate of death from any cause did not differ significantly between the double-dose and standard-dose groups (2.3% and 2.4%, respectively; hazard ratio with the double dose, 0.96; 95% CI, 0.82 to 1.13; P=0.61). Major bleeding occurred more often in the double-dose arm (2.5 vs 2.0% HR 1.24; 95% CI 1.05-1.46).For the aspirin comparison, the rate of primary outcome events did not differ: 4.2% in the higher-dose arm vs 4.4% in the lower-dose arm. Death from any cause was not statistically different in either arm. Major bleeding rates were also similar in the two aspirin arms (2.3% in both arms).The authors described a “nominally significant” interaction between clopidogrel dose and aspirin dose for the primary outcome. Among patients assigned to higher-dose aspirin, the primary outcome occurred in 3.8% of patients in the double-dose clopidogrel group, as compared with 4.6% of patients in the standard-dose clopidogrel group (hazard ratio, 0.82; 95% CI, 0.69 to 0.98; P=0.03). But in the lower dose aspirin group, there were no significant differences in the primary outcome between double-dose and standard-dose clopidogrel (4.5% vs 4.2% HR 1.07 95% CI 0.90-1.26, respectively). The p-value for the interaction here was 0.04. Subgroup analyses showed generally consistent results. One possible heterogenous treatment effect in the double- vs standard-dose clopidogrel comparison turned on whether the patient had PCI or did not have PCI. In the 68% (≈17,000) of patients who had PCI, double dose clopidogrel reduced the primary outcome by 15% (3.9% vs 4.5%) vs increasing it by 14% in the no PCI group (4.9% vs 4.3%). The p-value for interaction was 0.03. There were no indications of heterogenous treatment effects depending on aspirin.Conclusions In patients with ACS, double dose clopidogrel or aspirin compared to standard dose did not significantly reduce the composite endpoint of cardiovascular death, MI or stroke. Double dose clopidogrel did increase major bleeding with a NNH of approximately 200 patients. Treatment effect heterogeneity, favoring the double dose clopidogrel strategy, was suggested for patients undergoing PCI.This trial serves as a good example of the limitations of surrogate endpoints in predicting hard outcomes. Previous studies had demonstrated that higher doses of clopidogrel led to faster and more substantial platelets inhibition. The observed increase in bleeding events with double-dose clopidogrel supported these findings. Nonetheless, it did not correspond to better ischemic outcomes.As for the dose of aspirin, there was no added benefit (or increase in bleeding) with higher dose aspirin beyond 75-100 mg. Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: What should you do when you want to escape negative people of the community/subgroup you're in (but don't want to hamper your career)?, published by Polkashell on April 8, 2024 on The Effective Altruism Forum. I'm talking specifically of an EA group. Anyone have experiences or thoughts on if their local EA group became super toxic and was full of people that they thought were super questionable? What do you do when for instance, that group has a few people who are working on the same things you are (I.e, same career area) and so you feel that if you chose to work on your career separate from this community (instead of forcing yourself within it) your career would be hampered in some way? (Eg having to interact with them, not work with each other, same network where they might be community builders hosting events so you feel so unwelcome in those) I've for a while now felt a couple groups (not all) I've been in EA can be quite toxic, especially certain individuals. So it feels right to stay far away and not work with them at all. But you're worried since the talent pool is quite small it would be negative to not join forces in someway. I guess further, I've been feeling more disenthused with EA groups the past year, the group I was part of definitely had a lot of toxic community builders and members who said bad things, very red flag type things. It scares me to feel this way because it feels like it leaves me more alone among people who should care about things I do but they would actually seem not to (not all of them) and I think I could hamper my impact and career because I would be alone. It has made me seriously consider quitting EA and even the area I'm working on now just to be away from them because it's impossible not to interact with them if not. What advice does anyone have for me? Does anyone have similar experiences? How do you thrive in an EA career outside of EA when the network is so strong within EA? For instance if I want to work on X cause area but do not want to involve myself with EA specifically anymore, how can I be successful especially if the talent pool from where I'm from is quite small for that particular cause area? I keep thinking, if I distance myself from this pool then I might also distance myself from opportunity. Some people I think who are not super directly "EA" but are doing good work are Jess Whittlestone, Jaime Yassif, etc. (correct me if I'm wrong) Thoughts here? I'm really struggling with how I feel in this community and it's been really awful for my mental health. I feel like the community I was part of has been very unfair and yeah, toxic and if other people around the community I know not part of this group heard what they were doing or what they said they would think it were red flaggy. I might been roundabout there but this is a raw post/Q. I don't feel so comfortable talking to community health at the moment. I don't currently feel comfortable talking to the CH of my group too. But to be open, some of these experiences revolve: 1) intentionally sabotaging specifically people in the community 2) spreading false information about people in the community 3) badmouthing people in the community unfairly 4) being questionable in their EA intentions 5) showing signs of strong arrogance (entitled to someone's life information, throwing some mini tantrums when they're not chosen for job, etc. there are more but I don't think I should disclose that). If these people were to go around doing stuff would people recommend they be reported or flagged or not? Would people who might work with them want to know this stuff? It might look weird if I proactively told people this stuff, might make me a hypocrite. I'm not here to ruin people's careers or anything. But sometimes I feel very uneasy that I've just been quiet dealing with these pe...

Lancet 1996;347:561-68.Background In most of the prior AMI trials presented here, patients with non_ST-segment myocardial infarction (NSTEMI) and/or unstable angina were included with patients with ST-segment myocardial infarction (STEMI). Patients with NSTEMI usually represented about 1/3 of trial participants. It had become clear based on subgroup analyses from the previous trials that NSTEMI patients did not benefit from thrombolysis. So, while intravenous anticoagulation with heparin was not found to be beneficial in GISSI-2 or ISIS-3, where thrombolysis was also used, there remained the possibility that it may benefit patients with unstable coronary syndromes who were not candidates for thrombolytic therapy. This smaller trial represents a departure from the general eligibility criteria for the AMI trials that we have already reviewed. The Fragmin During Instability in Coronary Artery Disease (FRISC) study group sought to test the hypothesis that subcutaneous low-molecular-weight heparin, in combination with aspirin, reduces death and new cardiac events in patients with unstable CAD. For the purposes of this study, unstable CAD represents unstable angina and NSTEMI.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Patients Patients had to be men older than 40 years and women at least 1 year after menopause admitted to the hospital for chest pain within the previous 72 hours. All patients had to have either newly developed or increased angina symptoms during the previous 2 months or persisting chest pain with suspicion for AMI and at least one of the following ECG criteria: transient or persistent ST depression of ≥ 0.1 mV or T-wave inversion of ≥ 0.1 mV in at least 2 adjacent leads without pathological Q waves in the ischemic leads. Essentially, the authors were selecting patients with unstable angina or NSTEMIs and not STEMIs or completed infarcts. There were many exclusion criteria for the trial including the presence of conditions with an increased risk of bleeding, known renal or liver insufficiency, indications for thrombolysis, suspected myocarditis and many others; however, it is worth noting there was no upper age limit.Baseline characteristics There were 5,137 patients who met eligibility criteria and 1,506 (29%) were randomized. The 3 most common reasons for exclusion were risk of bleeding (20%), compliance problems (15%), and Q waves or bundle branch block (14%). Patients with other severe disease accounted for 4% of exclusions and those with renal or liver insufficiency accounted for 2%.The median age of participants was 69 years and approximately 65% were men. 20% of participants were active smokers, 13% had diabetes and nearly 30% had a previous heart attack. Patients with NSTEMI accounted for close to 40% of participants and the remainder had unstable angina.Procedures Treatment was started as soon as possible after admission. During the first 6 days (acute phase), 120 IU per kg bodyweight (maximum dose of 10,000 IU) of dalteparin or placebo was injected every 12 hr. There was then a home treatment phase. For the next 35-45 days—at home— 7,500 IU of dalteparin or placebo was injected once daily. Patients stayed in the hospital during the acute phase for at least 5 days and on day 5-8 were discharged with the lower home dose. On day 40-50, the treatment was stopped and the final follow-up visit was scheduled 5-7 months after trial enrollment.Endpoints The primary endpoint was the rate of death and new myocardial infarction during the first 6 days. Secondary endpoints were the rates of death and new MI after 40 and 150 days, the frequency of revascularization procedures and need for heparin infusion, and a composite endpoint. Cause of death and myocardial infarction were verified by the independent endpoint committee who had to differentiate a new event from an inclusion event. Safety endpoints included major and minor bleeding. Major bleeding was defined by a drop of ≥2 g/dL in hemoglobin with associated signs or symptoms of bleeding, and minor bleeding was any other bleeding not meeting the former criteria. A sample size of 1,500 was based on a power of 0.80 to detect a reduction in the primary composite endpoint from 6% to 3% at a 2-sided alpha of 5%. Subgroup analyses were prespecified and a “high-risk group” was defined by the presence of at least 2 of the following variables: age >70, previous MI, medically treated heart failure, or diabetes.Results 1,506 patients were included in the final analysis; 757 in the placebo group and 741 in the dalteparin group. At 6 days, dalteparin significantly reduced the occurrence of the primary endpoint (RR 0.37; 1.8% vs 4.8%; 95% CI 0.20-0.68), which was driven by myocardial infarction (RR 0.33; 1.4% vs 4.4%; 95% CI 0.16-0.60). There was no difference in death between groups (RR 0.88; 0.9% vs 1.1%; 95% CI 0.32-2.48) and minor bleeding events were much more common in the dalteparin group (8.2% vs 0.3%).At 40 (8.0% vs 10.7%) and 150 (14.0% vs 15.5%) days, differences between groups were less pronounced for the primary endpoint and the results, in favor of dalteparin, were not statistically significant. Bleeding events, driven by minor bleeding, continued to be much higher for the dalteparin group.Subgroup analyses are presented at 6 and 40 days and are generally concordant across subgroups, meaning the treatment effect goes in the same direction, but these analyses should be viewed skeptically as they represent small sample sizes, particularly compared to subgroups in the earlier mega trials. Subgroup data suggests concordant results for patients less than or greater than 70 years of age and for patients meeting high risk criterion compared to those not meeting it.Conclusions In patients with unstable angina and NSTEMI, dalteparin reduced the primary endpoint of death or nonfatal MI compared to placebo at 6 days and was associated with a NNT of 33 patients. This was driven by a reduction in nonfatal MI. The results were no longer significant at 40 or 150 days. This trial is limited by small sample size and highly selected patient population.Thank you for reading Cardiology Trial's Substack. This post is public so feel free to share it. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Claire chatted to Maria Jose (Marisé) Galvez Trigo from Cardiff University all about human-robot interaction, machine learning, and accessibility. Maria Jose Galvez Trigo (Marisé) is a Lecturer in the School of Computer Science and Informatics at Cardiff University, and part of the Human-centred Computing (HCC) Research Section and its Subgroup in Computational and Human-centred Robotics. Marisé is interested in Robotics, Human-Robot Interaction, Human-Computer Interaction and applications of Machine Learning in those areas, with accessibility and co-design as key aspects of her research. Within those areas, her research explores how the uptake of robotics systems can be improved. Win a Robot Talk T-shirt For a chance to win your very own organic cotton Robot Talk t-shirt, all you have to do is: Sign up to our newsletter Share our competition post on social media: Twitter, LinkedIn, Facebook, BlueSky, Threads or Mastodon You can enter across multiple platforms. One lucky winner will be randomly selected each month!  Find out more: https://www.robottalk.org/t-shirt-competition/.

In this episode of Carbless Conversations, we venture into the surprising intersection of Oreos, cholesterol, and statins in a bold experiment that challenges conventional wisdom. We will dive deep into a groundbreaking study conducted by Harvard medical student Nick Norwitz.  As we peel back the layers of this metabolic demonstration, the episode illuminates the nuances of this new "Lipid Energy Model" (LEM), the role of saturated fats, and the surprising efficacy of Oreos in lowering LDL cholesterol more dramatically than high-intensity statin therapy in people with a specific phenotype, namely the Lean Mass Hyper Responder (LMHR).  But it's not all cookies and cream; the conversation takes a critical look at the pharmaceutical industry's reliance on statins and the broader implications for those following a ketogenic diet.  With a blend of science and skepticism, this episode invites your brain to explode and for you to rethink everything you thought you knew about diet, cholesterol, saturated fat, and carbohydrates. Oreos Vs. Statins Study: https://www.mdpi.com/2218-1989/14/1/73 Keto/Low Carb/Carnivore recipes: https://trinakrug.com Keto/Low Carb/Carnivore/Diabetes Community: https://www.facebook.com/groups/335715249100159 Keto/Low Carb Recipes and Support Community: https://www.facebook.com/groups/1993303330779537 Email: trina@trinakrug.com   Please note that the content provided in this podcast is for informational purposes only and is not intended as professional advice. The views expressed by the hosts and guests are their own and should not be taken as expert guidance. While we strive to provide accurate and up-to-date information, we do not guarantee the completeness, reliability, or accuracy of this information. Listeners are encouraged to consult with a professional in the relevant field for any specific advice or information they may need. The creators of this podcast disclaim any liability for actions taken based on the content of this podcast.

This week we discuss the chronic neurological condition Multiple Sclerosis. Samantha Joseph BA (Hons), DipBCNH, mBANT, CNHC, is a Nutritional Therapist. Her husband Danny was diagnosed with MS in 2002 which led her to specialise in this area. She has been a guest lecturer for colleges of Integrative Nutrition covering modules on MS, Parkinson's disease, mental & behavioural health. In 2018 she joined the charity Overcoming MS as a senior facilitator. Samantha also worked together with the MS Academy (www.neurologyacademy.org) giving nutritional advice for their Healthy Living Services clinics and collaborated on the a paper pending in Frontiers of Neurology, highlighting holistic management of MS, https://linktr.ee/nutritionista_uk Karen Lee, previously intensive care nurse and practising registered nutritionist, combines her love of food with her professional background to inspire others to experience the powerful effects of food as medicine.  As ‘The Sensitive Foodie', Karen has run courses, workshops and cooking classes, and has a blog – The Sensitive Foodie Kitchen. In 2019, Karen published her first book Eat Well Live Well with The Sensitive Foodie and is currently working on her second. Karen is an Ambassador for Overcoming MS and helped to create The PBHP-UK factsheet on MS. She was co-author on a case study in The American Journal of Lifestyle Medicine. She is also Events Manager for Plant-Based Health Professionals UK. Website: https://thesensitivefoodiekitchen.com Facebook: https://facebook.com/thesensitivefoodie Instagram: https://Instagram.com/the.sensitive.foodie Historical Swank Evidence:  Swank RL, Dugan BB. Effect of low saturated fat diet in early and late cases of multiple sclerosis. Lancet. 1990 Jul 7;336(8706):37-9. Swank, RL. MS: a correlation of its incidence with dietary fat. Am J Med Sci. 1950;220:421-30  Bjørnevik, K. Polyunsaturated fatty acids and the risk of multiple sclerosis.  Multiple Sclerosis Journal,  2017. 23(14), 1830–1838  Jelinek GA, et al. Association of fish consumption and Ω 3 supplementation with quality of life, disability and disease activity in an international cohort of people with multiple sclerosis. Int J Neurosci. 2013 Nov;123(11):792-800 Esparza ML, et al. A brief original contribution: Nutrition, Latitude, and Multiple Sclerosis Mortality: An Ecologic Study. American Journal of Epidemiology, 1995. 142(7):733–737  Simpson-Yap S, et al. Longitudinal associations between quality of diet and disability over 7.5 years in an international sample of people with multiple sclerosis. Eur J Neurol. 2023 Jul 11. doi: 10.1111/ene.15980  Ayroza Galvão Ribeiro Gomes AB, et al. Immunoglobulin A Antibodies Against Myelin Oligodendrocyte Glycoprotein in a Subgroup of Patients With Central Nervous System Demyelination. JAMA Neurol. 2023 Aug 7:e232523 Agranoff BW & Goldberg D. Diet and the geographical distribution of multiple sclerosis. Lancet. 1974; 2:1061-6 Munger KL, et al. Vitamin D intake and incidence of MS. Neurology. 2004;62:60-5 Richards JB. Vitamin D and Risk of Multiple Sclerosis: A Mendelian Randomization Study., 2015. PLoS Medicine. Aug 25;12(8):e1001866 Hadgkiss EJ et al. The association of diet with quality of life, disability, and relapse rate in an international sample of people with multiple sclerosis. Nutritional Neuroscience. 2015;18(3):125-136. Fitzgerald KC, Tyry T, Salter A, Cofield SS, Cutter G, Fox R, Marrie RA. Diet quality is associated with disability and symptom severity in multiple sclerosis. Neurology. 2018 Jan 2;90(1):e1-e11. Simpson-Yap S, et al. Longitudinal associations between quality of diet and disability over 7.5 years in an international sample of people with multiple sclerosis. Eur J Neurol. 2023 Jul 11. doi: 10.1111/ene.15980 Evers I, et al. Adherence to dietary guidelines is associated with better physical and mental quality of life: results from a cross-sectional survey among 728 Dutch MS patients. Nutr Neurosci. 2022 Aug;25(8):1633-1640

Lancet 1988;349-360Background The introduction to the ISIS-2 manuscript opens with a remarkable statement from the authors:Reductions in mortality that are realistically moderate (eg, “only” 20-25%) are important, especially if produced by widely practicable treatments for common causes of death.At the time of this posting, January 2024, it's amazing to think, how in 1988, a 20-25% reduction in mortality was considered moderate for a “widely practicable treatment for a common cause of death” and now the profession seems to grasp at almost anything, at nearly any cost, that reduces some composite of hard, soft and, in some cases, completely meaningless endpoints by the same amount. Regardless, ISIS-2 sought to test the hypothesis that streptokinase and aspirin, either alone or together, would reduce vascular mortality in patients with MI.Patients Patients with suspected myocardial infarction, who the responsible physician thought were within 24 hours of symptom onset and had no clear indication for, or contraindication to, streptokinase or aspirin. Absolute contraindications included: any history of stroke or of gastrointestinal ulcer. Possible contraindications included: recent arterial puncture, recent severe trauma, severe persistent hypertension, allergy to streptokinase or aspirin, low risk of cardiac death, or some other life-threatening disease. ECG changes at entry were not required.The design was meant to be pragmatic to facilitate patient enrollment; however, exclusion criteria was more extensive for ISIS-2 compared to ISIS-1, which reflects concern about hemorrhagic side effects associated with use of these agents. Like ISIS-1, there were no special procedures dictating patient follow-up after the hospitalization ended.Baseline characteristics Basic demographic information is not provided in the main manuscript but we can infer from the subgroup Forest plots that more than two thirds of patients were men, the overwhelming majority were less than 70 years of age, and nearly half were less than 60. Less than 20% had a previous MI and only around 7% had diabetes. Patients with inferior and anterior STEMI's composed more than half of the cohort. About 43% of patients presented within 4 hours of symptom onset, another 42% presented between 5 and 12 hours, and the remaining 15% presented between 13 and 24 hours.Procedures A 2x2 factorial study design was used. All patients were randomly assigned to receive either streptokinase or a matching placebo. All patients were also randomly assigned to receive either aspirin or a matching placebo. This led to 4 distinct treatment groups: 1) streptokinase + aspirin placebo, 2) aspirin + streptokinase placebo, 3) streptokinase + aspirin, or 4) placebo onlyPatients allocated to receive streptokinase were immediately given 1.5 MU of ‘Streptase' over 1 hour. Patients allocated to receive aspirin were immediately given 162.5 mg of an enteric coated tablet that was crushed, sucked, or chewed for a rapid anti-platelet effect. Thereafter, they took a 162.5 mg tablet daily for 1 month.Endpoints Vascular mortality over 5 weeks was the primary endpoint. Follow-up after discharge involved only mortality, through government records wherever possible.Results 17,187 participants were randomized from 417 hospitals in 16 countries. Compliance with the assigned treatments was estimated to be between 90-95%.The results of ISIS-2 are not reported in a standard results table, making vascular mortality as well as all-cause mortality impossible to infer over the duration of the trial. The number of non-vascular deaths are presented in a table but vascular deaths beyond 5 weeks are not formally provided in the original publication. The only evidence of vascular deaths beyond 5 weeks is presented in survival curves.Over 5 weeks, Streptokinase alone reduced vascular mortality compared to placebo by approximately 25% (9.2% vs 12.0%) and these results were highly significant. The difference remained highly significant over the course of the trial. Non-vascular deaths accounted for a tiny fraction of all deaths (3.5%) and were unchanged between groups. Subgroup analysis of streptokinase efficacy based on time from pain onset showed it was more effective if given within 4 hours (8.2% vs 12.3%) vs between 5-24 hours (10.0% vs 11.8%).Streptokinase use was associated with higher rates of hypotension and bradycardia (10% vs 2.0%), allergic reactions (4.4% vs 0.9%), minor bleeding (3.5% vs 1.0%) and major bleeding (0.5% vs 0.2%). The bleeding excess appeared similar whether streptokinase was used with aspirin or not. Streptokinase was also associated with a small but significant risk of cerebral hemorrhage (7 vs 0 events) all of which were followed by death or severe disability. However, overall, streptokinase was not associated with an increase in stroke (0.7% vs 0.8%) or in the risk of disabling/fatal stroke (0.5% vs 0.6%).Aspirin alone reduced vascular mortality compared to placebo by 23%, approximately the same amount as streptokinase alone over 5 weeks (9.4% vs 11.8%), and these results were highly significant and remained so over the course of the trial. There were fewer non-vascular deaths among aspirin allocated patients, so all-cause deaths were also significantly reduced but like with streptokinase, non-vascular death accounted for a tiny fraction of all deaths. Unlike Streptokinase alone, the treatment effect of aspirin was unchanged regardless of when it was started relative to the onset of pain.Aspirin significantly increased minor bleeds (2.5% vs 1.9%) but there were no major differences in any other side effects.Streptokinase and aspirin compared to double placebo reduced vascular mortality nearly twice as much as either agent alone (8.0% vs 13.2%) and these results were highly significant and remained so over the course of the trial. Non-vascular deaths were the same between groups and so all-cause mortality was also significantly reduced by streptokinase and aspirin. Subgroup analysis based on time from pain onset demonstrated greater efficacy for those receiving treatment in under 4 hours (6.4% vs 13.1%) compared to those receiving treatment between 5-24 hours (9.2% vs 13.3%).Streptokinase and aspirin together were associated with increases in major and minor bleeding as well as cerebral hemorrhage that were similar to streptokinase alone both in terms of their relative and absolute differences.Additional subgroup analyses suggest that patients presenting with anterior STEMI's derived the greatest benefit from streptokinase alone and in combination with aspirin. The risk of death was about twice as high for patients presenting with an anterior vs inferior STEMI (15% vs 8%). Patient's presenting with ST depression on their ECGs experienced a similar overall risk of death compared to patients with anterior STEMI's but did not appear to derive a significant benefit from any combination of treatment.Conclusions Streptokinase alone and aspirin alone reduced death over 5 weeks compared to placebo. 30 to 40 patients would need to be treated with either agent alone to prevent 1 person from dying, which was very similar to the effect noted in the GISSI trial that tested Streptokinase alone. In ISIS-2, the combination of the 2 agents (Streptokinase and Aspirin) reduced death even further (nearly twice the effect of either agent alone) compared to double placebo controls and this was associated with an NNT of 20 or less. Streptokinase, whether alone or in combination with aspirin, exerted the greatest effect when given to patients presenting within 4 hours from pain onset but was still effective when given outside this window (subgroup stratification was not the same as GISSI, which showed that the benefit waned and possibly reversed after 6-9 hours). In ISIS-2 there was no evidence to suggest that sicker patients or those with larger MI's did worse (i.e, lower SBP, higher HR, or anterior STEMI) but again, not all subgroups presented were the same as in the GISSI trial, which did show less benefit for some higher risk groups. Like GISSI, ISIS-2 provided evidence that patients presenting with NSTEMI's did not benefit from streptokinase.In summation, ISIS-2, like the GISSI trial that preceded it, demonstrated the significant impact of early revascularization via thrombolysis on mortality in patients presenting with STEMI. It also demonstrated the significant benefit of aspirin and the additive effect of both agents together. To this day, the pillars of STEMI management involve aspirin and prompt revascularization, whether done via thrombolysis or PCI.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

Featuring an interview with Dr Joseph Mikhael, including the following topics: Daratumumab, carfilzomib, lenalidomide, and dexamethasone with minimal residual disease response-adapted therapy for newly diagnosed multiple myeloma (MM) (0:00) KRd versus elotuzumab and KRd for transplant-eligible patients with newly diagnosed MM (10:47) Subgroup analysis of patients with 1q21 and other cytogenetic abnormalities in the Phase III IKEMA and ICARIA-MM studies (15:12) Results with ciltacabtagene autoleucel among patients with relapsed/refractory (R/R) MM in the CARTITUDE-1 study (26:59) CARTITUDE-4 study: Ciltacabtagene autoleucel in earlier lines of treatment for patients with lenalidomide-refractory MM (34:56) KarMMa-3 trial: Idecabtagene vicleucel for patients with R/R MM (44:20) GPRC5D-targeted CAR (chimeric antigen receptor) T-cell therapy for patients with R/R MM (49:09) Efficacy of teclistamab for R/R MM in the MajesTEC-1 trial (53:45) Efficacy of elranatamab for R/R MM in the MagnetisMM-3 trial (58:43) Efficacy of linvoseltamab for R/R MM in the LINKER-MM1 trial (1:02:01) Talquetamab for patients with R/R MM in the MonumenTAL-1 trial (1:04:16) Future directions in the first-line management of MM (1:06:03) Strategies to improve diversity and inclusion in clinical trials (1:10:53) CME information and select publications

There is a new subgroup being added to SIN 541611 for Program Evaluation Services.  They have created a technical board to review all applicants to the new category, find out the details in the episode!As always if you have any questions, or if you'd like direct support from a GSA consultant to help with a specific project please feel free to reach out to us at podcast@elevategsa.com 

Welcome to the NeurologyLive® Mind Moments® podcast. Tune in to hear leaders in neurology sound off on topics that impact your clinical practice. In this episode, Thomas Crawford, MD, a pediatric neurologist at Johns Hopkins Medicine, spoke on the recently published 5-year analysis of the NURTURE study (NCT02386553), a long-term trial assessing the efficacy and safety of nusinersen (Spinraza; Biogen) in presymptomatic infants with spinal muscular atrophy (SMA). Crawford discussed the significance of the positive findings, the shift in conversations around treatment optimization in SMA, and how subgroup data may factor into the design of future trials. Looking for more Neuromuscular Disorders discussion? Check out the NeurologyLive® neuromuscular clinical focus page. Episode Breakdown: 1:20 – Benefits seen with nusinersen in NURTURE  4:10 – Changes in goals for treating SMA 6:05 – Complexities with getting infants therapy days after diagnosis 9:40 – Neurology News Minute 12:30 – Subgroup findings from NURTURE 15:20 – Ways to improve treatment optimization in SMA This episode is brought to you by Medical World News, a streaming channel from MJH Life Sciences®. Check out new content and shows every day, only at medicalworldnews.com. The stories featured in this week's Neurology News Minute, which will give you quick updates on the following developments in neurology, are further detailed here: World Health Organization Adds Several MS Treatments to List of Essential Medicines Ceribell's Status Epilepticus Software Receives FDA Clearance With CMS NTAP Coverage Included FDA Accepts New Drug Application for Long-Acting Form of Glatiramer Acetate Essential Tremor Agent Ulixacaltamide Continues to Show Positive Results in Essential1 Study Thanks for listening to the NeurologyLive® Mind Moments® podcast. To support the show, be sure to rate, review, and subscribe wherever you listen to podcasts. For more neurology news and expert-driven content, visit neurologylive.com.

The Mission of St. Stephen's United Methodist Church is to make disciples of Jesus Christ for the transformation of the world. To learn more about St. Stephen's or to view our full online services please visit wwww.ststephensfairfax.org

This episode is sponsored by Charm Economics– data-driven solutions for digital health & MedTech businesses. Dr. Block and his guest, Dr. Ken Milne, delve into the concept of knowledge translation and the time it takes for new information to be integrated into clinical practice. They reference a famous paper that found it takes an average of 17 years for clinically relevant information to reach the patient's bedside.  However, the hosts believe that this time frame can be shortened with the help of social media and evidence-based medicine. They emphasize the importance of evidence-based medicine but also note that it should not be the only factor in decision-making. The hosts also discuss their checklist for evaluating the validity of studies and how they use their podcast to share new information with their audience. Overall, the hosts believe that shortening the time it takes for new information to be integrated into clinical practice can lead to improved patient outcomes. The episode also touches on the potential benefits of vitamin C in treating sepsis patients. One study conducted at Dr. Paul Merrick's Institution showed a significant mortality benefit in patients who were given a cocktail of thiamine, Vitamin C, and hydrocortisone. However, the study was not a randomized control trial and was before-and-after observational, leading to skepticism about the conclusions. Over the next few years, properly designed randomized control trials were conducted and found that vitamin C had no significant impact on sepsis patients. Therefore, while there was initial interest in the potential benefits of vitamin C in treating sepsis, further research has shown that it is not an effective treatment. Looking for something specific within the show? Here you go! [00:00:00] Evidence-based medicine in practice.  [00:05:27] Knowledge translation takes 17 years.  [00:07:26] Randomized control trial questions.  [00:10:59] Shared decision-making in medicine.  [00:14:53] Evidence-based medicine in emergency room.  [00:18:18] Physicians' big egos.  [00:22:20] TXA: The Duct Tape.  [00:24:01] Health interventions and cost.  [00:27:46] Subgroup analysis in studies.  [00:31:12] Epistemology and scientific bias.  [00:34:32] Vitamin C and its benefits.  [00:38:17] Losing to get better. Guest bio: Dr. Milne is a staff physician at Staff at South Huron Hospital Association in Exeter, Ontario, Canada. He has been doing medical research for over 35 years publishing on a variety of topics. Dr. Milne has been working clinically for 25 years and is an adjunct professor in the Department of Medicine (Division of Emergency Medicine) and Department of Family Medicine at the Schulich School of Medicine and Dentistry. He teaches evidence-based medicine, clinical epidemiology, critical appraisal and biostatistics at Western University in London, Ontario. Dr. Milne is passionate about skepticism and critical thinking. He is the creator of the knowledge translation project, The Skeptics' Guide to Emergency Medicine (TheSGEM). Ken is married to Barb and has three amazing children. Dr. Milne serves as a senior editor of Academic Emergency Medicine. He has no funding from the pharmaceutical or biomedical device industry. He is on faculty for the Center for Medical Education and EMRAP. Dr. Milne does partake in medical malpractice reviews and does hold a patent on a pediatric resuscitation device. Connect with Dr. Milne on his LinkedIn.  Did ya know…  You can also be a guest on our show? Please email me at brad@physiciansguidetodoctoring.com to connect.  Socials: @physiciansguidetodoctoring on FB  @physicianguidetodoctoring on YouTube @physiciansguide on Instagram and Twitter

Dr. Deidre O'Connor is an Assistant Professor and Chair of the Disability Subgroup at the University College Dublin in Dublin Ireland. Today she'll be telling us about the subgroup's work. Learn more about University College Dublin's Disability Subgroup by checking out their website via the link below: https://www.ucd.ie/equality/groups/disabilitysub-group/ We mentioned the "Atelier für Alle" disability-oriented art program: https://www.atelierfuralle.org If you have any questions about this show please send them to: atelierfuralle@gmail.com Feel free to leave a review of this show.

The authors report that applicants to undergraduate health professions education prefer selection methods that provide a sense of control and allow the demonstration of more than just academic ability.   Read the accompanying article to this podcast:  https://onlinelibrary.wiley.com/doi/10.1111/medu.14949

The JournalFeed podcast for the week of Feb 6 to 10, 2023.These are summaries from just 2 of the 5 article we cover every week! For access to more, please visit JournalFeed.org for details about becoming a member.Zinc Vs. COVID Spoon FeedZinc supplementation for patients with COVID-19 decreased 30-day ICU admission rate and led to shorter symptom duration. Subgroup analysis showed these effects were especially pronounced for elderly patients and those with comorbid conditions.Tubing in Angioedema Spoon FeedIn patients presenting with angioedema, history of hypertension, shortness of breath, drooling, and anterior tongue or pharyngeal swelling were risk factors for eventual need for intubation.

For patients with ER+/HER2- advanced breast cancer, current treatment guidelines recommend the use of endocrine therapy plus a CDK 4/6 inhibitor as a first-line treatment. And while the guidelines recommend sequential endocrine therapy for disease progressions, this progression can lead to ESR1 mutations and resistance to endocrine therapy. Could a novel oral selective estrogen receptor have more efficacy in preventing ESR1 mutations associated with endocrine resistance? That's the exact question the EMERALD trial sought to answer, and what this study found in its subgroup analyses is the focus of this Audio Abstract.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.06.519361v1?rss=1 Authors: Broeren, B. O., Hundepool, C. A., Kumas, A. H., Duraku, L. S., Walbeehm, E. T., Hooijmans, C. R., Power, D. M., Zuidam, J. M., De Jong, T. Abstract: Background: Treatment of nerve injuries proves to be a worldwide clinical challenge. Acellular nerve allografts are suggested to be a promising alternative for bridging a nerve gap to the current gold standard, an autologous nerve graft. Objective: To systematically review the efficacy of the acellular nerve allograft, its difference from the gold standard (the nerve autograft) and to discuss its possible indications. Material and methods: PubMed, Embase and Web of Science were systematically searched until the 4th of January 2022. Original peer reviewed paper that presented 1) distinctive data; 2) a clear comparison between not immunologically processed acellular allografts and autologous nerve transfers; 3) was performed in laboratory animals of all species and sex. Meta analyses and subgroup analyses (for graft length and species) were conducted for muscle weight, sciatic function index, ankle angle, nerve conduction velocity, axon count diameter, tetanic contraction and amplitude using a Random effects model. Subgroup analyses were conducted on graft length and species. Results: Fifty articles were included in this review and all were included in the meta-analyses. An acellular allograft resulted in a significantly lower muscle weight, sciatic function index, ankle angle, nerve conduction velocity, axon count and smaller diameter, tetanic contraction compared to an autologous nerve graft. No difference was found in amplitude between acellular allografts and autologous nerve transfers. Post hoc subgroup analyses of graft length showed a significant reduced muscle weight in long grafts versus small and medium length grafts. All included studies showed a large variance in methodological design. Conclusion: Our review shows that the included studies, investigating the use of acellular allografts, showed a large variance in methodological design and are as a consequence difficult to compare. Nevertheless, our results indicate that treating a nerve gap with an allograft results in an inferior nerve recovery compared to an autograft in seven out of eight outcomes assessed in experimental animals. In addition, based on our preliminary post hoc subgroup analyses we suggest that when an allograft is being used an allograft in short and medium (0-1cm, greater than 1-2cm) nerve gaps is preferred over an allograft in long ( greater than 2cm) nerve gaps. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

In this podcast, we discuss the article 'Perioperative critical events and morbidity associated with anesthesia in early life: Subgroup analysis of United Kingdom participation in the Neonate and Children audit of Anaesthesia Practice IN Europe (NECTARINE) prospective multicenter observational study'. We hope you enjoy.

In this episode, Jubilee Brown, MD, and Elisabeth Diver, MD, provide expert insights on new data presented at ASCO 2022 for ovarian, endometrial, and cervical cancers regarding:Subgroup analyses from KEYNOTE-826 evaluating pembrolizumab in combination with chemotherapy with or without bevacizumab in persistent, recurrent, or metastatic cervical cancerPreliminary subgroup analyses from phase III ENGOT-EN5/GOG-3055 SIENDO trial of selinexor vs placebo maintenance in recurrent endometrial cancerUpdated analyses from phase I GARNET trial of dostarlimab in dMMR/MSI-H and pMMR/MSS advanced/recurrent endometrial cancer (cohorts A1 and A2)EndoBARR trial of atezolizumab, bevacizumab, and rucaparib in previously treated recurrent and progressive endometrial cancerPhase III ATHENA-MONO trial of first-line rucaparib vs placebo maintenance after platinum-based chemotherapy in patients with advanced ovarian cancerPresenters:Jubilee Brown, MDProfessor and Division DirectorGynecologic OncologyLevine Cancer Institute, Atrium HealthCharlotte, North CarolinaElisabeth Diver, MDClinical Assistant ProfessorDivision of Gynecologic OncologyDepartment of Obstetrics and GynecologyStanford UniversityStanford Cancer InstituteStanford University Hospital and ClinicsStanford, CaliforniaContent supported by educational grants from AstraZeneca, GlaxoSmithKline, Karyopharm Therapeutics, and Merck Sharp & Dohme Corp.Link to full program, including a downloadable highlights slideset, and ClinicalThought commentaries:https://bit.ly/3ufB8Js

Guest host Dr. Vamsi Velcheti, of the NYU Langone Perlmutter Cancer Center, and Dr. Brian Henick, of the Columbia University Herbert Irving Comprehensive Cancer Center, discuss advances in KRAS-mutated lung cancer in the KRYSTAL-1 trial, and the association of ctDNA with overall survival in the NADIM trial, as well as other key advances in lung cancer presented at the 2022 ASCO Annual Meeting.   TRANSCRIPT   Dr. Vamsi Velcheti: Hello, everyone! This is Dr. Vamsi Velcheti, I'm your guest host for the ASCO Daily News podcast, today. I'm an associate professor and medical director for the Thoracic Oncology Program at Perlmutter Cancer Center at NYU Langone Health. My guest today is Dr. Brian Henick, an associate director of the Experimental Therapeutics Program, and assistant professor of Medicine at Columbia University's Herbert Irving Comprehensive Cancer Center. We'll be discussing key abstracts in lung cancer that were featured at the 2022 ASCO Annual Meeting. Our full disclosures are available in the notes and disclosures of all guests on the podcast can be found on the transcripts at asco.org/podcasts. Brian, it's great to speak with you today. Dr. Brain Henick: Thank you so much, Vamsi, and ASCO Daily News for letting me join you to discuss these abstracts. Dr. Vamsi Velcheti: So, let's dive in. So, it's an exciting ASCO Annual Meeting. And I hope you had a great time at the Meeting. So, let's start off with the LBA9009 and KRYSTAL-1 clinical trial. The study showed the activity of adagrasib in patients with KRAS-G12C mutant non-small cell lung cancer and active untreated brain mets. So, what is the key takeaway from this trial? Dr. Brain Henick: Well, Dr. Sabari presented some encouraging data on this important population. As we know, patients with active central nervous system (CNS) metastases represent a population of unmet medical need who are often excluded from clinical trials. So, it's a credit to the investigators for including this cohort. As Dr. Sabari noted, and as Dr. Goldberg emphasized in her discussion of the abstract, the measured CNS penetration of adagrasib compares favorably with other CNS active compounds from other settings. The overall response rate was 35%, with a disease control rate of 80%. But impressively, the median duration of intracranial response and progression-free survival (PFS) wasn't reached. This certainly seems to be a CNS active compound, and we'll need to see how sotorasib stacks up in their comparable cohort. Ideally, we'd have randomized data to prove superiority over the standard of care, but we may be a few steps away from that. Dr. Vamsi Velcheti: So, Brian, in terms of CNS mets, how big of a problem is it in patients with KRAS G12C mutant lung cancers? Dr. Brian Henick: We know that CNS metastases are a big problem for G12C mutant lung cancer. The rates have been quoted as high as up to 42% of patients. And in particular, as you know, Vamsi, a lot of times trials often don't include, specifically, cohorts with active untreated brain metastases. And so, this is a very unique cohort in that sense. Dr. Vamsi Velcheti: I just want to highlight that we really don't know the differential efficacy of sotorasib and adagrasib in the CNS met population because the trials were CodeBreak 100 and other trials and data readouts from sotorasib did not include patients with untreated brain mets. We did, however, [see] CNS progression-free survival data that go in line with sotorasib. So, it's really important to see that data from sotorasib. Dr. Brain Henick: I definitely look forward to seeing that. Dr. Vamsi Velcheti: So, let's talk about Abstract 8501. The primary endpoint that was presented at ASCO [Annual Meeting] was the pathologic complete response to chemotherapy and nivo vs. chemotherapy as a new adjuvant treatment for resectable stage 3, a non-small cell lung cancer. This was the phase 2 NADIM trial. So, what do you think about this study? And what's your key takeaway from the study? Dr. Brain Henick: Dr. Provencio from Spain presented data from this randomized study as you said, of nivo plus carbo taxol compared to carbo taxol as neoadjuvant therapy for potentially resectable stage 3-A and B non-small cell lung cancer. So, I did want to compare this to the randomized data that we have from Checkmate 816, which interestingly allowed for earlier-stage disease as low as 1-B. And they also allowed for more flexibility in the choice of platinum doublet regimens. This study, NADIM 2, employs 2:1 versus 1:1 randomization, which we saw in Checkmate 816. Another important difference was that NADIM 2 required adjuvant nivolumab for 6 months in the study arm, whereas Checkmate 816 didn't include any immunotherapy in the adjuvant setting, but they allowed for a standard of care chemotherapy. In NADIM 2, the control arm didn't include any adjuvant therapy. In keeping with the impressive improvements over historical pathologic complete response rates of about 5%, this chemotherapy-IO regimen yielded a path complete response (CR) rate of 36.8%. It also showed a major pathological response, which again is defined as less than 10% viable tumor of 52.6%, and an overall response rate of 75.4%. So, it looks like there's a benefit that's happening upfront with the immunotherapy and chemotherapy as opposed to this just being an adjuvant phenomenon. This is also in keeping with data that we saw with Checkmate 816, as well as neoadjuvant atezo plus chemotherapy in the phase 2 study that was led by Catherine Shu and colleagues here at Columbia a few years ago. Overall, this is more encouraging data for the neoadjuvant use of immunotherapy. The earlier immunotherapy marches into the treatment course of patients with lung cancer, the greater the cost of toxicity. So, I think an important thing for us to focus on going forward is trying to develop strategies to better identify the patients that are most likely to benefit. Dr. Vamsi Velcheti: So, Brian, I think from a practical standpoint, now that we have approval for neoadjuvant immunotherapy and adjuvant immunotherapy, we have some practical challenges in terms of how we manage our patients. Of course, the new adjuvant is very appealing because it's only 3 cycles of chemoimmunotherapy, but the challenge though, is a majority of the patients don't have a CR, or a significant proportion of the patients have an ongoing response or significant residual disease at the time of surgery. So, the question then would be what do you do after surgery if they're having an ongoing response? Do you think 3 cycles of immunotherapy are inadequate systemic therapy for these patients? Dr. Brian Henick: It's a really important question, Vamsi. I think until the data is mature, we're just kind of limited by the extent of what the data tells us so far, and then we have to kind of do our best as the treating doctor to navigate the patient's situation. So, tools that we'd still have available to us in the adjuvant setting that are approved are things like chemotherapy and radiation, leveraging things like circulating tumor DNA, I think maybe a promising path forward, as well to help guide strategies there, but I think until the data is mature, it has to be highly patient-focused to figure out what seems to be most appropriate there. How are you navigating those situations, Vamsi? Dr. Vamsi Velcheti: Yeah, as you said, it is very challenging. I think we need more data. And of course, the challenge now is like, if you use immunotherapy in the new adjuvant setting, it's very likely you're not going to get insurance authorization for 1 year of adjuvant atezolizumab. So, we really need studies to optimize treatment paradigms here. As you suggested, maybe circulating tumor DNA (ctDNA)-based approaches to look at residual disease, I think, that would be one great way to do it. Let's move on to the next abstract, Brian. I found Abstract 9001 really interesting. It's a U.S. Food and Drug Administration (FDA) pooled analysis that looked at outcomes of first-line immune checkpoint inhibitors, with or without chemotherapy based on the KRAS mutation status and PD-L1 expression. So, what is your take on this abstract and how do you think this is going to impact our practice? Dr. Brian Henick: So, Dr. Nakajima and colleagues explored the observation from individual trials that patients with KRAS-mutant lung cancer seem to have better responses than wild type with immunotherapy (IO) alone. But the favorability of these responses seems to be abrogated with chemotherapy-IO. We know that KRAS accounts for 25% of oncogene-driven non-small cell lung cancer predominantly at amino acid 12. And with the emergence of direct inhibitors of G12C, understanding the clinical features of these tumors may be critical to inform optimal integration of this new class of drugs and also to make sure that we've optimized treatment algorithms for KRAS patients in general. So, this study's authors at the FDA pulled data from 12 registrational clinical trials that were investigating first-line checkpoint inhibitor-containing regimens and they found no significant difference between KRAS wild type and mutant for overall survival regardless of the regimen used. The best outcomes were seen with chemoimmunotherapy regardless of KRAS status. This retrospective analysis does suggest that the notion of there being lesser benefit from chemoimmunotherapy from Dr. Gadgeel's study might not hold up in the overall population, but I think it raises important questions, like, are all KRAS mutations alike? The absence of KRAS mutation status for a majority of patients included in these studies limits the interpretation of the data. And also, the absence of commutation status makes it a little harder to interpret. And other important questions remain such as how G12C inhibitors will factor in? What were your thoughts, Vamsi? Dr. Vamsi Velcheti: No, I completely agree with you, Brian. I think we need more data and we know that commutation status is a very important aspect in terms of KRAS-directed therapies. And of course, with a lot of promising data from these KRAS inhibitors, there's an interest in moving these drugs into the front-line therapy for patients with KRAS mutations. But I think it's going to be quite challenging to incorporate them into the front-line therapies and we clearly will need better characterization of these patients with KRAS mutant [lung cancer] to further personalize treatment in the frontline setting for these patients. So, let's move on to the next abstract. This is the lung map study, Abstract 9004. This is a study sponsored by the National Cancer Institute (NCI), the lung map study, looking at overall survival from a phase 2 randomized study of ramucirumab and pembrolizumab, what's the standard of care in patients with advanced non—small cell lung cancer previously treated with immunotherapy. So, what were your key takeaway points here from this study? Dr. Brian Henick: So first of all, it's very exciting to see data from this very ambitious long map sub-study yield a positive result. Whereas many of the arms of this study were biomarker-guided, Dr. Reckamp presented the results from pembro plus ramucirumab as compared to the standard of care in unmarked patients with non-small cell lung cancer who had progressed after prior treatment with chemotherapy and immunotherapy. The data seems to suggest that pembro plus ramucirumab may be better tolerated than the standard of care chemo-containing regimens, as the experimental regimen had fewer serious adverse events. Pembro plus ramucirumab had a median overall survival of 14.6 months as compared to 11.6 months in the control arm and this was statistically significant. The PFS difference wasn't significant, but there was a late divergence in the curves. Dr. Bestvina nicely summarized some of the study's limitations such as the mixture of control regimens used, and there were really interesting signals that were found on subgroup analysis, such as benefit in those with mixed histology tumors, STK11 mutant tumors, and those who received chemotherapy prior to immunotherapy. The subgroups deserve further attention in the future. For now, this regimen may be an appealing option as an alternative to chemotherapy for the right patients. What do you think? Dr. Vamsi Velcheti: Yeah, I agree, Brian. I think it's a really promising combination. We've always seen some synergy with VEGF inhibitors and immunotherapy in multiple studies and multiple tumor types. So, we really need to develop better ways to select patients for VEGF combination-based approaches in lung cancer. So, let's move on to another interesting study. This is Abstract 9000. This explores the outcomes of anti-PD-L1 therapy with or without chemotherapy for first-line, metastatic non-small cell lung cancer with a PD-L1 score of greater than 50%. So, this is an FDA pooled analysis. So, what were your key takeaways from this abstract? Dr. Brain Henick: I thought this question was really well suited for a large pooled retrospective analysis and our colleagues at the FDA didn't let us down here. The question really was what's the optimal approach for patients with non-small cell lung cancer with greater than 50% PD-L1 in view of the absence of direct comparisons between these arms in prospective studies? I thought one of the most striking findings from Dr. Akinboro's presentation was the dismally low rate of underrepresented minority patients that were included in these registration trials. As far as the findings for the patients who were studied, although the Kaplan-Meier curves for overall survival showed early separation, the difference wasn't statistically significant. Subgroup analysis revealed a trend towards better outcomes for immunotherapy alone among patients who are [age] 75 and above, suggesting that this may need to be parsed out as a unique population in subsequent studies. But in all, our equipoise as a field on whether to include chemoimmunotherapy-based first-line regimens should persist and should be guided, in my opinion, largely by clinical considerations. Can the patient tolerate chemotherapy? Do you need a rapid response? Are there other things that you thought in hearing all this, Vamsi? Dr. Vamsi Velcheti: Yeah, absolutely. I think I am still struggling with the decision of whether to add chemotherapy for patients with greater than 50%. To a large extent, it's actually a clinical decision. In some patients who have a large disease burden, I tend to kind of opt for adding chemotherapy to immunotherapy in the front-line setting. But of course, we need more data here. And this is actually a very helpful piece of information from the FDA. And as you pointed out briefly, Brian, I think the fact that there are very few underrepresented patients in the pooled analysis, I think kind of speaks to the need for addressing increased diversity in clinical trial accruals. I think this is a great segue to also talk about Abstract 9012, talking about disparities in access to immunotherapy globally. This is a study from India looking at 15,000 patients who were checkpoint inhibitor eligible and who have very low rates of uptake of immunotherapy. This is something that reflects the global team of the ASCO Annual Meeting talking about disparities and improving access to treatments in underserved minority populations here in the United States, and also globally, in the developing world, the disparities in terms of access to care are humongous. So, what are your thoughts, Brian? And also, if you could highlight some of the work that you're doing at Columbia about disparities, I think that would be great. Dr. Brain Henick: Absolutely! I think access to medications is a really humbling topic for those of us who are involved in developmental therapeutics, particularly with the transformational impact we've seen with the advent of immunotherapy over the last decade-plus. Dr. Ravikrishna's presentation is therefore extremely important. He described very low rates of uptake of immunotherapy by indication. And perhaps most strikingly, the discrepancy in uptake by patients' ability to pay for therapy with the vast majority of immunotherapy received by those who are private is very concerning. Even if the definition of restricted access was permissive, for example, I didn't see mention of the cancer stage as an eligibility factor, the fact that this represents a single referral center's data doesn't bode well for uptake elsewhere. So, I think we need to continue to work as a field on prioritizing strategies to help overcome these gaps, but good quality data such as this study is an important first step. And to that point, Vamsi, I'm very excited to be working with you in collaboration on an observational study for patients with lung cancer from underserved minority populations with lung cancer in New York City so that we can better characterize access to care, efficacy, and toxicity in this population. Dr. Vamsi Velcheti: Thank you, Brian. I'd really like to thank you for sharing your valuable insights with us today on the ASCO Daily News Podcast. We really appreciate it. Brian, thank you so much for joining us. Dr. Brain Henick: My pleasure. Thanks for having me. Dr. Vamsi Velcheti: And thank you to all our listeners for joining in today. You will find links to all the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. Thank you so much.     Disclosures: Dr. Vamsi Velcheti: Honoraria: Honoraria Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline Dr. Brain Henick: None disclosed. Disclaimer: The purpose of this podcast is to educate and inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Show Notes:The Art of Gathering: How we meet and why it matters by Priya Parker The Essential Guide for Small Group Leaders by Bill SearchWhy does a group get tired? •Leader begins to coast•Meeting becomes routine•Relationships hit a plateau•Purpose is lost#1 Leader Coasting Am I practicing “Generous Authority”? – [Priya Parker] “'Chill' is selfishness disguised as kindness.” - Priya Parker Generous Authority Serves others by: 1.Protecting group members 2.Equalizing group members 3.Inter-Connecting group members We practice Generous Authority by:1.Practicing good MANNERS in the group 2.Reminding all of the “RULES” 3.Encourage “Sprout” Speeches not “Stump” Speeches Now What?1. Re-affirm Covenant 2. Have tough conversations3. Re-up as the leader or get out 4. Share Leadership #2 Meeting Routine “The room is doing 80% of the job” – Jerry Seinfeld Venue Matters 1.The space should be a symbol of reason for meeting 2.The space should bring out desired behaviors and discourage those you don't 3.Consider density Format Matters 1.Mix it up2.Curtail the dull parts 3.Try different curriculum Now What? 1. Rotate Hosting 2. Share testimony3. Serve together4. Choose an unlikely meeting place #3 Relationships Plateaued Why does this happen? 1.We stop being curious about others 2.We decide how far we will go relationally3.Potential conflict zones are avoided 4.We don't feel safe What can you do about it? 1.Don't avoid the awkward – embrace it 2.Utilize GOOD ice-breakers 3.Encourage people to share what no one in the group would guess/ know about them4.Talk about the forbidden subjects of politics, sex, and religion 5.Don't stop conflict but guide it 6.Navigate underlying conflicts Now What? 1. Split by gender 2. Subgroup for prayer3. Retreat4. Day trip, local restaurants, or local tourism #4 Lost Purpose “A good gathering purpose should be ‘disputable'” – The Art of Gathering by Parker Start by asking “WHY are we meeting?” 1.First, ask the church leadership 2.Reverse engineer current meeting and compare to stated goal 3.Who is this for? Second ask “Why are WE meeting?” 1.Is our goal the same as the leadership's goal? 2.Do we have a different goal? Third, re-state and re-affirm your purpose 1.Discuss the purpose as a group 2.Arrive at consensus3.Everyone has to re-up That didn't work. Now what? How to End Your Group (Page 87, Essential Guide for Small Group Leaders) 1.Understand all groups come to a natural end 2.Get input from group members3.Ask everyone to make a personal plan 4.Plan a final meeting and put it on the calendar5.End the group in a prayer circle6.Don't forget to tell your pastor or small group coach that your group has ended Recommended Resources: Dare to Lead by Brene BrownThe Art of Gathering By ParkerEssential Guide for Small Group Leaders by Search Questions? 

Show Notes:The Art of Gathering: How we meet and why it matters by Priya Parker The Essential Guide for Small Group Leaders by Bill SearchWhy does a group get tired? •Leader begins to coast•Meeting becomes routine•Relationships hit a plateau•Purpose is lost#1 Leader Coasting Am I practicing “Generous Authority”? – [Priya Parker] “'Chill' is selfishness disguised as kindness.” - Priya Parker Generous Authority Serves others by: 1.Protecting group members 2.Equalizing group members 3.Inter-Connecting group members We practice Generous Authority by:1.Practicing good MANNERS in the group 2.Reminding all of the “RULES” 3.Encourage “Sprout” Speeches not “Stump” Speeches Now What?1. Re-affirm Covenant 2. Have tough conversations3. Re-up as the leader or get out 4. Share Leadership #2 Meeting Routine “The room is doing 80% of the job” – Jerry Seinfeld Venue Matters 1.The space should be a symbol of reason for meeting 2.The space should bring out desired behaviors and discourage those you don't 3.Consider density Format Matters 1.Mix it up2.Curtail the dull parts 3.Try different curriculum Now What? 1. Rotate Hosting 2. Share testimony3. Serve together4. Choose an unlikely meeting place #3 Relationships Plateaued Why does this happen? 1.We stop being curious about others 2.We decide how far we will go relationally3.Potential conflict zones are avoided 4.We don't feel safe What can you do about it? 1.Don't avoid the awkward – embrace it 2.Utilize GOOD ice-breakers 3.Encourage people to share what no one in the group would guess/ know about them4.Talk about the forbidden subjects of politics, sex, and religion 5.Don't stop conflict but guide it 6.Navigate underlying conflicts Now What? 1. Split by gender 2. Subgroup for prayer3. Retreat4. Day trip, local restaurants, or local tourism #4 Lost Purpose “A good gathering purpose should be ‘disputable'” – The Art of Gathering by Parker Start by asking “WHY are we meeting?” 1.First, ask the church leadership 2.Reverse engineer current meeting and compare to stated goal 3.Who is this for? Second ask “Why are WE meeting?” 1.Is our goal the same as the leadership's goal? 2.Do we have a different goal? Third, re-state and re-affirm your purpose 1.Discuss the purpose as a group 2.Arrive at consensus3.Everyone has to re-up That didn't work. Now what? How to End Your Group (Page 87, Essential Guide for Small Group Leaders) 1.Understand all groups come to a natural end 2.Get input from group members3.Ask everyone to make a personal plan 4.Plan a final meeting and put it on the calendar5.End the group in a prayer circle6.Don't forget to tell your pastor or small group coach that your group has ended Recommended Resources: Dare to Lead by Brene BrownThe Art of Gathering By ParkerEssential Guide for Small Group Leaders by Search Questions? 

Ministry doesn't have to be a mystery. Attend an ALIGN workshop this March and get the basic and next steps of Small Group ministry. ALIGN will give you a foundational understanding of small groups and a plan for taking your church to the next level. But the most valuable part of an ALIGN workshop are the connections you'll make. Because no one should have to do ministry alone.ALIGN Irvine in Orange County, California is March 24thALIGN Atlanta at 1st Baptist Woodstock in Woodstock Georgia is March 31stFor more details, go to https://smallgroupnetwork.com/align-workshops/We can't wait to see you there!Show Notes:The Art of Gathering: How we meet and why it matters by Priya Parker The Essential Guide for Small Group Leaders by Bill SearchWhy does a group get tired? •Leader begins to coast•Meeting becomes routine•Relationships hit a plateau•Purpose is lost#1 Leader Coasting Am I practicing “Generous Authority”? – [Priya Parker] “'Chill' is selfishness disguised as kindness.” - Priya Parker Generous Authority Serves others by: 1.Protecting group members 2.Equalizing group members 3.Inter-Connecting group members We practice Generous Authority by:1.Practicing good MANNERS in the group 2.Reminding all of the “RULES” 3.Encourage “Sprout” Speeches not “Stump” Speeches Now What?1. Re-affirm Covenant 2. Have tough conversations3. Re-up as the leader or get out 4. Share Leadership #2 Meeting Routine “The room is doing 80% of the job” – Jerry Seinfeld Venue Matters 1.The space should be a symbol of reason for meeting 2.The space should bring out desired behaviors and discourage those you don't 3.Consider density Format Matters 1.Mix it up2.Curtail the dull parts 3.Try different curriculum Now What? 1. Rotate Hosting 2. Share testimony3. Serve together4. Choose an unlikely meeting place #3 Relationships Plateaued Why does this happen? 1.We stop being curious about others 2.We decide how far we will go relationally3.Potential conflict zones are avoided 4.We don't feel safe What can you do about it? 1.Don't avoid the awkward – embrace it 2.Utilize GOOD ice-breakers 3.Encourage people to share what no one in the group would guess/ know about them4.Talk about the forbidden subjects of politics, sex, and religion 5.Don't stop conflict but guide it 6.Navigate underlying conflicts Now What? 1. Split by gender 2. Subgroup for prayer3. Retreat4. Day trip, local restaurants, or local tourism #4 Lost Purpose “A good gathering purpose should be ‘disputable'” – The Art of Gathering by Parker Start by asking “WHY are we meeting?” 1.First, ask the church leadership 2.Reverse engineer current meeting and compare to stated goal 3.Who is this for? Second ask “Why are WE meeting?” 1.Is our goal the same as the leadership's goal? 2.Do we have a different goal? Third, re-state and re-affirm your purpose 1.Discuss the purpose as a group 2.Arrive at consensus3.Everyone has to re-up That didn't work. Now what? How to End Your Group (Page 87, Essential Guide for Small Group Leaders) 1.Understand all groups come to a natural end 2.Get input from group members3.Ask everyone to make a personal plan 4.Plan a final meeting and put it on the calendar5.End the group in a prayer circle6.Don't forget to tell your pastor or small group coach that your group has ended Recommended Resources: Dare to Lead by Brene BrownThe Art of Gathering By ParkerEssential Guide for Small Group Leaders by Search Questions? 

Subgroup analyses in combination with data visualisation is one of the hottest topics I can think about. And it hits us as statisticians during our careers again and again. We need to understand subgroups for efficacy reasons and safety reasons and it's a common question in terms of how consistent your drug works across the different subgroups. It gets even more complicated if you want to review it across multiple studies.

Dr. Neeraj Agarwal, ASCO Daily News editor-in-chief, and director of the Genitourinary Cancers Program at the University of Utah's Huntsman Cancer Institute, shares key takeaways from the practice-changing ARASENS trial in mHSPC, featured at the 2022 ASCO Genitourinary Cancers Symposium.   Transcript: ASCO Daily News: Hello, and welcome to the ASCO Daily News podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. Today in our continuing coverage of the 2022 ASCO Genitourinary (GU) Cancer Symposium. Dr. Neeraj Agarwal, the editor in chief of the ASCO Daily News will share key takeaways from the practice-changing ARASENS trial, which showed promising results in metastatic hormone-sensitive prostate cancer. Dr. Agarwal has no conflicts relating to the topic of this episode and his full disclosures are available in this show notes. Disclosures of all guests on the podcast can be found in our transcripts at asco.org/podcasts. Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News podcast. I'm Dr. Neeraj Agrawal, the director of the Genitourinary Cancers Program and professor of medicine at the University of Utah Huntsman Cancer Institute. Let's discuss the results of the practice-changing ARASENS trial in patients with metastatic castration-sensitive prostate cancer as presented at the 2022 ASCO GU Symposium. This abstract, Abstract 13, was presented by Dr. Matthew Smith from the Massachusetts General Hospital and Hartford Medical School. ARASENS is a randomized phase 3 trial evaluating the efficacy and safety of darolutamide, a novel hormonal therapy, plus ADT (antiandrogen therapy) plus docetaxel versus placebo plus ADT plus docetaxel in patients with metastatic castration-sensitive prostate cancer. Randomization was stratified by the extent of disease and alkaline phosphatase levels, below versus upper limit of normal or above. It is important to know that this study only included patients that were eligible for ADT and docetaxel chemotherapy, to begin with. The primary endpoint was overall survival with multiple secondary endpoints, including time to CRPC (castration-resistant prostate cancer), time to pain progression, time to first symptomatic skeletal event, and time to start off the next anti-neoplastic therapy, and safety. A total of 1,306 patients were randomly assigned to triplet therapy with darolutamide plus ADT plus docetaxel versus placebo plus ADT plus docetaxel. Baseline characteristics were well balanced between the treatment arms. Analysis of the primary endpoint was pre-specified. After, 533 events had occurred results show the primary endpoint of this study was met with a significant improvement in overall survival and a 32.5% reduction in risk of death for patients on the triplet therapy on for darolutamide plus ADT plus docetaxel versus placebo plus ADT plus docetaxel. It is important to know that the triplet therapy improved overall survival, despite 76% of patients in the control arm having received the next life-prolonging therapy. Subgroup analysis indicates consistent benefit across the 3 specified groups. Secondary endpoints also were favored by the triplet therapy combination over the control arm. While this study offers an additional excellent option for our patients with metastatic cancer-sensitive prostate cancer in older populations, the use of docetaxel may be a significant limitation to this triplet combination. In addition, and importantly, this study did not answer the question of whether adding docetaxel chemotherapy to the ADT plus novel hormonal therapy backbone will also improve survival. With the advent of multiple doublets and triplet combinations in recent years, as we saw in the form of ADT plus enzalutamide ADT plus apalutamide in the recent years, it is very important to find biomarkers that may predict response to these treatment options, which will allow personalization of therapy with that. I would like to conclude this podcast on the ARASENS trial. Thank you very much for your kind attention. ASCO Daily News: You've been listening to Dr. Neeraj Agarwal of the University of Utah's Huntsman Cancer Institute. Thanks for joining us today. If you're enjoying the content on the podcast, please take a moment to rate and review us wherever you get your podcasts. Disclosures: Dr. Neeraj Agarwal: Consulting or Advisory Role: Pfizer, Medivation/Astellas, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Merck, Novartis, lily, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, ORIC Pharmaceuticals, CRISPR therapeutics, and Arvinas Disclaimer: The purpose of this podcast is to educate and to inform this is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

When I hear the word " change ", I hear HAVING THE CHOICE. ... _______________________ CONNECT on Facebook https://www.facebook.com/groups/503166600709551/?ref=share ________________________ CONNECT on Instagram https://instagram.com/survivingtheodds_thepodcast?utm_medium=copy_link _________________________ CONNECT on YouTube https://youtube.com/channel/UCUDx2Q2iEZXEeCsZmM4WkHw ________________________ MENTOR Facebook@Spiritual Success Sorrority https://www.facebook.com/groups/SpiritualSuccessSorority/?ref=share _________________________ MENTOR on Facebook @Shessobossmindsetincubator https://www.facebook.com/groups/shessobossmindsetincubator/?ref=share _______________________ CONNECT on Facebook @Om Vision https://www.facebook.com/groups/122399858477116/?ref=share ___________________________________________________________________________ SUPPORT THIS PODCAST @https://linktr.ee/strokesto _________________________ JOIN MY TRAUMA WARRIOR TRIBE, SUBGROUP on Facebook https://www.facebook.com/groups/1140238053097474/?ref=share _________________________ Medical Disclaimer The content shared here is not intended to be a substitute for professional medical advice, care, diagnosis, or treatment. Always seek the advice of a qualified & licensed Healthcare professional. ■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■■ I'm a Survival coach specializing in Stroke survivors. 1- helping to find & accept the new identity. 2-Readdapt in day to day life. 3- Heal from this trauma. CALL WHAT'S APP 1-514-993-4454

How do I take down property and make sure the numbers work? How do I own and manage that property and make sure I have cash flow? - Look no further, let Garrick O'Connell helps you here from acquisition to financing, to property management, to possibly disposition and networking. So... Get ready… It's time to get some deeper insights from our expert guest for this episode one of the Subgroup Leader with Garrick O'Connell.  __ Garrick O'Connell Bio: Originally from San Diego CA, Garrick O'Connell growing up near the ocean he enjoyed action sports such as ocean kayaking, deep-sea fishing, snorkeling,  and practiced martial arts that taught him to seek adventure and discipline. Before landing in Arizona he had been working for a successful architecture and construction consulting firm in San Diego actively helping real estate owners and investors fix everything that can go WRONG with real estate where he developed a love and appreciation for buildings and homes. After reaching his peak in consulting he decided to seek a new adventure and no longer watch from the sidelines so he could help with everything that can go RIGHT with real estate. I have now been in Tempe for 2 years enjoying all it has to offer and working in the Central and uptown phoenix corridor as well. New homeownership, home sales, helping homeowners become investors, and experienced investors expand their portfolios. -- 

In Today's episode, let's welcome our special guest Patrick Allen.  Patrick Allen is a licensed real estate agent who moved to Tucson in 2013 from Nashville, TN. A former ultra-endurance triathlon coach, Patrick has a passion for helping home buyers and real estate investors alike accomplish their goals of buying their first, or next, property. Patrick enjoys serving his community through outreach programs surrounding investing and financial independence. In his free time, Patrick enjoys playing kickball, traveling, drinking craft beer and morning walks with his dog Artemis.  Make sure to listen to the full episode as Patrick discusses finding deals, how newbies can get started, and the Tucson group curriculum. Whether you are an experienced investor with a large portfolio, or just getting started and looking to secure income and wealth through real estate investing the AZREIA Show is here for you. This podcast provides you with exceptional education, resources, and support to help you further your real estate career. Our community consists of independent real estate investors who utilize a myriad of investment strategies. If you're looking to learn from the most successful investors in the industry then you have found your new home.   KEY TAKEAWAYS IN THIS EPISODE: 03: 14 Get to know Patrick Allen  06: 35 Real estate as a side hustle transition to full-time  07:47 The most straightforward ways to get started investing if you don't have a lot of capital. 13:13 Patrick provides service to the residents of Tucson  14:32 Patrick's primarily looking at Tucson market right now 15:49 Connect with Patrick  18:06 Benefits of being a member of Patrick's Subgroup in Tucson. 21:20 The beginning of Patrick's Subgroups in Tucson area (story revealed) 22:17 What is “Deal funnel at the top” 23:26 Newbie investors curriculum to learn real estate investing with Patrick (pretty polished) 27:42 Patrick's most intriguing part about being a Sub Group Leader. 28:49 Philosophy of “Why is this the next step?” 30:56 Characteristics that a newbie  investor should have in order to reach the level of success. 34:13 Azreia Calendar of Events.  Find out more about our guest at: https://www.biggerpockets.com/users/pat_allen Email: patrick@teamintegritytucson.com  Phone: 520.275.7368   ----- Thanks for listening to the AZREIA SHOW Podcast with Marcus Maloney and Michael Del Prete. Don't forget to subscribe to the show on iTunes and leave a rating and review. See you on our next episode!   To learn more about investing and to understand your investor identity to the free Entrepreneur Self Assessment at: https://azreia.org/entrepreneurial-self-assessment/  Azreia Real Estate Investing Entrepreneurial Self Assessment Who is if for? Anyone who wants to know if Real Estate Investing is right for them BEFORE spending time or money on education and training. Everyone new to Real Estate Investing Our Entrepreneurial Self Assessment is designed for you to understand if Real Estate Investing is right for you and if so, you are best suited for active or passive investing.   Join our conversation at: Facebook:   Twitter:  Instagram:  Website: LinkedIn:        

Whether you are an experienced investor with a large portfolio, or just getting started and looking to secure income and wealth through real estate investing the AZREIA Show is here for you. This podcast provides you with exceptional education, resources, and support to help you further your real estate career. Our community consists of independent real estate investors who utilize a myriad of investment strategies. If you're looking to learn from the most successful investors in the industry then you have found your new home. In today's episode, our special guest is Allan Woodruff he a Design Engineer, an Investor, an Electrical Contractor, an MBA, or a sales manager in the Asia Pacific region? These are all steps along the path. In 1968, Allan Woodruff left graduate school, moved to California, and started a career in technology. Within four months he bought his first duplex and was off and running as a part-time investor. His goal was simple: acquire enough properties that would pay themselves off over the next 30 years, so that they would then generate enough cash flow to allow him to break free. With this mission in mind, he was able to enjoy his high-tech career, and casually invest in real estate with a buy-hold strategy. He still enjoys the sport of the game. It's not all about the money... it's an art form, it's providing housing, it's improving the community. And it's fun. As a believer in building body, mind, and spirit, he's conscious of putting being into his doing. KEY TAKEAWAYS: 2:23 Get to know Alan Woodruff 7:03 How did Allan get his first duplex 30 days after he read a book? 12:50 The joy of providing housing to tenants kept Allan's passion & mission burning throughout the years 21:50  Allan's investment in different cities was a product of his market research & extensive analysis 29:04 Investing out of state as a result of ‘Serendipity' 30:27 Tips about finding contractors on both local or outside markets—REVEALED! 33:19 How did Allan bounce back after a mistake? 35:10 Allan bought deals out of state through CASH. How did he do that?       ----- Thanks for listening to the AZREIA SHOW Podcast with Marcus Maloney and Michael Del Prete. Don't forget to subscribe to the show on iTunes and leave a rating and review. See you on our next episode! To learn more about investing and to understand your investor identity to the free Entrepreneur Self Assessment at: https://azreia.org/entrepreneurial-self-assessment/  Azreia Real Estate Investing Entrepreneurial Self Assessment Who is if for? Anyone who wants to know if Real Estate Investing is right for them BEFORE spending time or money on education and training. Everyone new to Real Estate Investing Our Entrepreneurial Self Assessment is designed for you to understand if Real Estate Investing is right for you and if so, you are best suited for active or passive investing.   Join our conversation at: Facebook:   Twitter:  Instagram:  Website: LinkedIn:  

Guest: Xiaohong Wang, MD, PhD Association of Biomarker Cutoffs and Endoscopic Outcomes in Crohn's Disease: A Post Hoc Analysis From the CALM Study Walter Reinisch, Remo Panaccione, Peter Bossuyt, Filip Baert, Alessandro Armuzzi, Xavier Hébuterne, Simon Travis, Silvio Danese, William J Sandborn, Stefan Schreiber, Sofie Berg, Qian Zhou, Kristina Kligys, Ezequiel Neimark, Ahmed A Suleiman, Geert D'Haens, Jean-Frederic Colombel Background: CALM was a randomized phase 3 trial in patients with Crohn's disease (CD) that demonstrated improved endoscopic outcomes when treatment was escalated based on cutoffs for inflammatory biomarkers, fecal calprotectin (FC), C-reactive protein (CRP), and CD Activity Index (CDAI) remission vs CDAI response alone. The purpose of this post hoc analysis of CALM was to identify drivers of treatment escalation and evaluate the association between biomarker cutoff concentrations and endoscopic end points. Methods: The proportion of patients achieving CD Endoscopic Index of Severity (CDEIS)

Date: March 31st, 2021 Guest Skeptic: Prof Daniel Fatovich is an emergency physician and clinical researcher based at Royal Perth Hospital, Western Australia. He is Head of the Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research; Professor of Emergency Medicine, University of Western Australia; and Director of Research for Royal Perth […]

The Bootstrap Marketing Subgroup chatted with Prof Dan Ariely, author of numerous books explaining the vagaries of human behavior and choice. Subgroup lead and BootRap Producer, Brian Massey interviewed Dan about his research and book, Predictably Irrational, and how these insights could be used in marketing and pricing. Brian provides a summary of the book in the first section and the interview begins at: 8:44. Topics covered include: Decoy Model, the power of comparison; social vs market exchange; price anchoring and Starbucks; TiVo v DVRs; fe/male differences in purchasing; the challenges of focus groups and bad data; anti-depressants vs placebos; the importance of moving marketing earlier in the product-creation process; design for physical AND cognitive differences; how the 2008 mortgage crisis was created by short-circuited human decision-making; how credit cards separate consumption from experience; Gucci, Prada & fakes; why consuming gas is stressful; the pain of pain; how lawyers should charge for their services; and much more. Dan also provides advice on how to appreciate the pain associated with the entrepreneurial journey. The conversation ends with a fascinating puzzle, the answer to which reveals our own proclivity to being "predictably irrational!" BootRap ATX is produced by Brian Massey of the Intended Consequences Podcast.