Podcasts about sbp

The Lancet Volume 353, Issue 9146 p9-13 January 02, 1999Background: Accumulating data at the time suggested functional benefits of antagonism of beta-adrenoreceptors in patients with heart failure. Multiple specific beta-blockers were being tested in trials. The CIBIS 1 trial found a trend towards 20% lower mortality in the bisoprolol (a highly cardio-selective beta-blocker) group and 30% fewer admissions to hospital for worsening heart failure. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II) trial was designed to test this evidence further.Patients Eligible patients had New York Heart Association Class III-IV symptoms with LVEF ≤ 35% and were stable on diuretics and ACE-inhibitors. Exclusion criteria included recent MI or coronary intervention, AV block or resting heart rate less 60 bpm and systolic BP < 100 mmHg. Patients already on beta-blockers or with planned therapy with beta-blockers were also not enrolled.Cardiology Trial's remains independent, free of industry ads, due to reader generosity. Please consider becoming a free or paid subscriber.Baseline Characteristics The mean age of patients was 61 years, 81% male, and 83% Class III. The mean LVEF was 28%. About half the patients had ischemic heart disease, 12% primary dilated cardiomyopathy and nearly 40% had a mixture of valvular heart disease, hypertensive heart disease or unproven ischemic disease.The mean SBP on enrollment was 130 mmHg and resting HR was 80 bpm. The mean duration of heart failure before enrollment was 3.5 years. About 20% had AF at baseline. Nearly all patients were on ACE-I and half were on digoxin.Trial Procedures There was no run-in period. CIBIS II was double blinded. Slightly more than 2,600 patients were randomized 1:1 to bisoprolol or placebo in 274 hospitals across 18 countries.Patients in the bisoprolol group were started at 1.25 mg daily and titrated up weekly to as high as 10 mg daily. The goal was to attempt the highest tolerated dose. Patients were seen every 3 months.Endpoints The primary endpoint was all-cause mortality. Secondary endpoints included all-cause hospital admissions, cardiovascular mortality, combined CV death and CV hospital admissions, and premature treatment withdrawals.The authors estimated a 11.2% mortality in the placebo group and powered the trial to find a 25% reduction in death in the bisoprolol arm over 2 years.Results The trial was sopped early (mean follow-up 1.3 years) after the planned second interim analysis for benefit. The primary outcome of all-cause death occurred in 11.8% in the bisoprolol group vs 17.3% in the placebo arm (HR 0.66 (95% CI 0.54-0.81, p < 0.0001)).Bisoprolol reduced sudden death (3.6% vs 6.3%), all-cause hospitalization (33% vs 39%), CV death (9% vs 12%). Permanent treatment withdrawal occurred in 15% of both arms.The subgroup analysis showed no substantial treatment heterogeneity. The most common dose was 10 mg daily reached in 43% of patients.Conclusion The 34% reduction in death was clinically meaningful and statistically robust. Our confidence in such a large effect size stems from a) previous data on beta-blockers, which found similar effects, b) the 42% reduction in sudden death in the bisoprolol arm and c) the large reductions in all-cause hospitalization. In addition, the trial conduct appeared strong with almost no lost-to-follow up. The lack of run-in period strengthens the external validity of CIBIS II.The same caveats seen in the US carvedilol trial also apply to CIBIS II, namely that patients were ambulatory, outpatients, mostly with Class III symptoms. Patients enrolled in the trial had a mean SBP of 130 mmHg and a resting heart rate of 80. Nearly all patients were tolerating ACE-I and half were taking digoxin. In addition, patients were started on low-dose and gradually titrated higher. The majority of patients were on higher than 5 mg daily.The authors warned against applying these results to non-ambulatory patients with Class IV symptoms, especially if there was recent instability. Get full access to Cardiology Trial's Substack at cardiologytrials.substack.com/subscribe

14th ACC 2025: SBP < 130 mmHg Linked to Reduced CV Mortality in Adults +80 Y

Lancet 1999;353:2001-07Background: Beta-blockers directly reduce cardiac contractility and myocardial oxygen demand. For decades, they were avoided in patients with acute and chronic heart failure over concerns they would facilitate decompensation of the condition. The therapeutic cornerstones of treatment, prior to the modern era of clinical trials, focused on managing symptoms and quality of life with diuretics and inotropic agents like digoxin; however, new paradigms were arising that focused on addressing neurohormonal mechanisms of chronic disease that were over-activated in the failing heart. The first major success came with inhibition of the renin angiotensin aldosterone system with angiotensin converting enzyme inhibitors whose effect on mortality for patients with mild and severe forms of chronic heart failure were demonstrated in the V-HEFT II, CONSENSUS, and SOLVD trials. Additional benefits were demonstrated with the mineralocorticoid receptor antagonist spironolactone in the RALES trial. These drug classes primarily work by reducing afterload and volume retention. Appreciating why they work for improving cardiac performance and managing symptoms in heart failure patients is straightforward when we consider the major factors that effect cardiac stroke volume - preload, afterload and contractility; however, it is also noteworthy the effects these agents have on sudden death. How beta-blockade benefits the failing heart is less obvious (outside prevention of sudden death). Mechanistic studies in patients with chronic heart failure have consistently shown that when beta blockers are used for more than 1 month, left ventricular function improves. Beta blocker therapy appears to restore the density of beta-adrenergic receptors after they have been downregulated by the chronic overactivity of the sympathetic nervous system. The first major placebo-controlled RCT to demonstrate a mortality benefit used the non-selective beta blocker carvedilol. The trial was small and not originally designed to test mortality and was stopped early without clearly predefined stopping rules. Furthermore, 8% of total patients selected for participation in the trial were excluded prior to randomization after a 2 week, open-label run-in phase with the study drug, which saw 2% of all patients experience worsening heart failure or death representing 24 patients (the difference in total deaths between groups was 9 when the trial was stopped). The Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF) was the first large scale trial designed to test the hypothesis that beta-blockade with metoprolol controlled/extended release (CR/XL) added to optimum medical therapy reduces mortality in patients with chronic systolic heart failure.Patients: Patients were recruited from 313 sites in 13 European countries and the United States. Eligible patients were men and women between the age of 40 to 80 years with symptomatic heart failure (NYHA class II-IV) for >/= 3 months before randomization. They had to be on a diuretic and ACE inhibitor for at least 2 weeks. Other drugs, including digoxin, could also be used. Patients also had to have an EF of /=68 beats per minute.Patients were excluded if: they had an MI or unstable angina within 28 days; had an indication or contraindication for treatment with beta-blocker; beta blockade within 6 weeks; heart failure due to systemic disease (i.e., amyloidosis) or alcohol abuse; scheduled or performed cardiac transplant; an ICD; procedures such as CABG or PCI planned or performed in the past 4 months; 2nd or 3rd degree AV block unless a pacemaker was present; unstable or decompensated heart failure defined by pulmonary edema or hypoperfusion or supine systolic BP 25% deviation of the number of observed versus expected consumed placebo tablets during the run-in period.Baseline characteristics: The mean age of patients was 64 years and approximately 78% were male. Slightly more than 30% of patients were above the age of 70. The average EF was 28%. The average SBP was 130 mmHg and heart rate was 82 bpm. Most patients had mild to moderate heart failure, with 41% in NYHA Class II, 56% in Class III, and only 3% in Class IV. Ischemic cardiomyopathy accounted for 65% of cases and nonischemic causes accounted for 35%. Most patients were on an ACE inhibitor or ARB (95%) and diuretic (90%). Digoxin was used in 63%. Trial procedures: Prior to randomization, the study was preceded by a single-blind, 2-week placebo run-in period. Patients meeting eligibility were then randomized to placebo or metoprolol CR/XL. The starting dose of placebo or metoprolol CR/XL was 12.5 mg daily for patients in NYHA class III or IV and 25 mg daily for patients in NYHA class II. The dose was doubled every 2 weeks until the target dose of 200 mg daily was reached. Patients were followed every 3 months.Endpoints: The primary outcome was all-cause mortality. It was estimated that 3,200 patients would need to be followed for 2.4 years to detect a 30% relative reduction in mortality based on annual mortality rate of 9.4% in the placebo group. This would achieve at least 80% power with a 2-sided alpha of 0.04. Patients were recruited faster then planned and so the final sample size of 3,991 patients increased the power of the study.The study was monitored by an independent safety committee and predefined stopping rules for efficacy were based on all-cause mortality, done when 25%, 50%, and 75% of expected deaths had occurred. Results: The trial was stopped early after the 2nd preplanned interim analysis when 50% of expected deaths had occurred. The mean duration of follow-up at the time of stopping was 1 year. The mean daily dose of metoprolol CR/XL was 159 mg once daily, with 87% receiving 100 mg or more and 64% receiving the target dose of 200 mg daily. In the placebo group, the corresponding values were 179 mg daily, 91% and 82%. The study drug was discontinued permanently in 14% of patients in the metoprolol group and 15% in the placebo group. Six months after randomization, heart rate decreased by 14 bpm in the metoprolol group compared to only 3 bpm in the placebo group. Systolic blood pressure decreased less in the metoprolol group (-2.1 vs 3.5 mmHg).Compared to placebo, metoprolol significantly reduced all-cause mortality (7.3% vs 10.8%; RR 0.66; 95% CI 0.53—0.81). Cardiovascular mortality accounted for 91% of all deaths; with sudden death accounting for 58% and death from worsening heart failure accounting for 24% of all deaths. All 3 of these causes of death were significantly reduced by metoprolol. The relative and absolute effects on death were greatest for patients with NYHA class III heart failure.Conclusions: In this trial of stable patients with mild to moderate chronic systolic heart failure, who were optimized on an ACEi or ARB and diuretic, metoprolol CR/XL significantly reduced all-cause mortality. Approximately 30 patients would need to be treated with metoprolol compared to placebo for 1 year to prevent 1 death. This trial represents a significant win for beta blockade in patients with chronic systolic heart failure. While the NNT in this trial is slightly higher than in SOLVD, it is important to appreciate that follow-up time in SOLVD was more than 3x longer. Limitations to external validity in this trial include the run-in period and stringent inclusion and exclusion criteria. Our enthusiasm is also tempered by early stopping, which has been found to be associated with false positive or exaggerated results but this concern is mitigated to some extent in this trial because the rules for early stopping were clearly defined in the protocol.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

Please join us at patreon.com/tortoiseshack "Ireland, once a proud republic of ideas and insurgents, now resembles a serfdom for supranational capital. It is time – long past time – for a reckoning. The question is not whether this gilded scaffolding will crumble. It is whether we will have the courage to build something real in its place." Business Post editorial May 2025 That's not a paragraph we expected to read from the SBP, so we had to dig into what was behind it. Joining us to do so is one of the authors of the Tax Mirage report, UCD Professor, Aidan Regan, and he breaks it down brilliantly. Don't miss this episode. Read the report here:https://democracychallenged.com/2025/05/07/irelands-1-trillion-mirage-how-a-nation-became-a-vault-for-global-profits/ Prof Richard Murphy on Keir Starmer - "Keir Starmer came out as a full-on racist" interview out now here:https://www.patreon.com/posts/patron-exclusive-129009639 Donate to Dignity for Palestine:https://www.patreon.com/posts/dignity-for-to-126186702

Are you planning for your U.S. Army retirement? If so, this week's Soldier for Life Podcast episode includes everything that you will need to know for your retirement planning journey! Listen as CW3 (Ret.) Lynn Peterson - the RSO Program Manager for the Army Retirement Services Office and our all-around retirement planning guru - shares LOADS of information and resources about planning steps, retirement resources and where to find them, major things to consider (including financial considerations, employment, healthcare, retirement locations, family considerations), veteran benefits, and SO much more! There were WAY too many great resources and links to websites/pages included in the podcast to include them all in this post, but here are a few to get you started (be sure to listen all the way through so you don't miss any of the fabulous resources that are available to you!):

N Engl J Med 1986; 314:1547-52Background Into the mid-1980's, digoxin and diuretics were the mainstay of chronic disease management for congestive heart failure. Vasodilator agents were also commonly used based on limited data of their favorable hemodynamic effects. No sufficiently powered trials in this space had been performed to assess whether administration of vasodilators or any other agents improved long-term morbidity or mortality for heart failure patients. The V-HEFT trial was undertaken to test the hypotheses that 2 widely used vasodilator regimens (prazosin or a combination of hydralazine and isosorbide dinitrate) were superior for reducing death versus placebo. The trial was sponsored by the Veterans Administration and only enrolled men.Patients Men between the ages of 18 and 75 were recruited from 11 participating Veterans Administration hospitals and had to have chronic congestive heart failure based on either evidence of cardiac dilatation or left ventricular dysfunction (EF 0.7 ng/mL and euvolemic volume status. Clinical evaluations and exercise-tolerance tests on 2 consecutive visits, two weeks apart, had to reveal clinical and exercise stability before randomization could occur. Following randomization, patients continued to receive the optimal dose of digoxin and diuretic along with 1 of 3 study regimens. The placebo group was given placebo tablets and placebo capsules and instructed to take them 4 times a day. The prazosin group took 2.5 mg prazosin capsules and placebo tablets 4 times a day. The hydralazine-isosorbide dinitrate group took 37.5 mg hydralazine capsules and 20 mg isosorbide dinitrate tablets 4 times a day.In all groups, therapy began with 1 capsule and 1 tablet to be taken 4 times a day. In the absence of side effects, this was increased to 2 capsules and 2 tablets 4 times a day for a total of 20 mg of prazosin or 300-160 mg of hydralazine-isosorbide dinitrate. If drug-related side effects occurred, the dose could be reduced to half a tablet 4 times per day or to one capsule 2 times per day. If the dose was reduced, an attempt was made later to reinstitute the full dose.In order to limit dropouts, rigorous criteria were established for “treatment failures.” Physicians were advised to hospitalize patients with worsening symptoms, and, if appropriate, to use temporary intravenous vasodilator or inotropic interventions for stabilization. Physicians were encouraged to resume study medications upon discharge. At least 2 such hospitalizations were required, along with objective evidence of deterioration, before the study medications were discontinued and replaced with known therapy.Endpoints The primary endpoint was all-cause mortality.Results 642 patients were enrolled (273 in placebo group, 183 in prazosin group and 186 in the hydralazine-isosorbide dinitrate group). Excluding discontinuations that took place within 1 month before death, 47 patients (17%) discontinued one or both types of placebos, 43 patients (23%) discontinued prazosin, and 60 patients (32%) discontinued either one or both drugs in the hydralazine-isosorbide group. Six months after randomization, the average prescribed doses were 18.6 mg per day of prazosin, 270 mg per day of hydralazine, and 136 mg per day of isosorbide dinitrate. More than 85% of the prescribed drugs were taken in each treatment group.The mean follow-up was 2.3 years (range 6 months to 5.7 years). Only 4 patients were lost to follow up (2 in placebo group, 1 in prazosin group, and 1 in hydralazine-dinitrate group). There were 120 deaths in placebo group (44%; 19 per 100 patient years), 91 in the prazosin group (50%; 22 per 100 patient years), 72 in the hydralazine-dinitrate group (39%; 17 per 100 patient years). A reduction in mortality over the entire follow-up period was observed in the hydralazine-nitrate group compared with placebo (p = 0.093 on the log-rank test and p = 0.046 on the generalized Wilcoxon test, which gives more weight to treatment differences occurring in the earlier part of the mortality curves and less weight to the latter part, where the numbers are smaller). The absolute difference in mortality between these groups increased during three years and then began to diminish. The absolute difference in mortality between the placebo group and hydralazine-isosorbide groups at years 1 through 4 was 7%, 9%, 11% and 4%, respectively.Prespecified subgroup analysis in CAD vs no CAD stratification showed no significant treatment effect heterogeneity for hydralazine-nitrate among those with CAD although the absolute difference in mortality between groups was numerically higher for patients with CAD.At 8 weeks and 1 year, SBP (-4.1 and -4.6 mmHg) and DBP (-3.2 and -2.7 mmHg) decreased the most in the prazosin group compared to placebo. Hydralazine-nitrate was not associated with a statistically significant nor clinically significant difference in BP with exception of DBP at 8 weeks. The EF rose significantly at 8 weeks and 1 year in the hydralazine-nitrate group (+2.9 and +4.2) compared to placebo but not in the prazosin group.Side effects were reported in 4.0% of placebo patients, 11% of prazosin patients and 19% of hydralazine-nitrate patients, respectively. The most common side effects were headache and dizziness. Headache was reported in 12% of hydralazine-nitrate patients.Conclusions This study compared the combination of hydralazine-isosorbide dinitrate or prazosin to placebo in patients with chronic congestive heart failure who were optimized on digoxin and diuretic therapy. In what appears to be a young (58 years) and highly selected population of clinically stable, male veterans with dilated cardiomyopathies and low symptom burdens, the combination of hydralazine-isosorbide reduced death by 2 per 100 patient years, increased EF by 4% at 1 year and did not significantly alter BP compared to placebo. Side effects were reported in approximately 1 out of 5 patients with the most common being headache and approximately 1 out of 3 discontinued 1 or both study drugs. Prasozin did not reduce death or increase EF but did reduce BP compared to placebo. The internal validity of the study is high with only a few minor imbalances in baseline characteristics, which do not appear clinically relevant nor to consistently favor any one group. Less than 1% of patients were lost to follow up with no significant imbalances between groups. The external validity is limited by the fact that this is a population of male veterans and the etiologic distribution of cardiomyopathy and heart failure is likely different from a general heart failure population; etiologic causes of death are also likely to be different. Furthermore, the population is highly selected and its unclear how many patients from the general heart failure population would meet study criteria.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

A recent 12-week randomised controlled trial involving healthy adults aged 55-70 yielded significant positive findings regarding pomegranate extract's effect on blood pressure. While the study might not have shown significant differences compared to placebo across all initially measured markers, it revealed important reductions within the group taking pomegranate extract daily. Specifically, participants supplementing with pomegranate extract saw a statistically significant average decrease in Systolic Blood Pressure (SBP) by 5.22 mmHg and Diastolic Blood Pressure (DBP) by 3.6 mmHg. The researchers highlight the potential clinical relevance of the SBP reduction, noting that a 5 mmHg drop is associated with an estimated 10% decrease in the risk of major cardiovascular events. These findings align with previous research and meta-analyses confirming pomegranate's blood pressure-lowering effects, suggesting pomegranate extract could be a supportive strategy for hypertension prevention in older adults."This information is for educational purposes only and should not be interpreted as medical advice.""The study discussed was a randomised controlled trial in healthy adults aged 55-70.""The significant positive findings highlighted are the reductions in Systolic and Diastolic blood pressure observed within the group taking pomegranate extract. The authors note the SBP reduction is potentially clinically relevant.""These blood pressure findings are consistent with other studies and meta-analyses on pomegranate, strengthening the evidence for this specific effect.""Always consult with a qualified healthcare professional before making any changes to your diet, supplement regimen, or treatment plan, especially regarding blood pressure management or if you have existing health conditions or take medications.""This channel is not monetized and does not provide medical advice."#PomegranateExtract, #BloodPressure, #SystolicBloodPressure, #ClinicalRelevance, #HypertensionPreventionFarhat G, Malla J, Vadher J, Al-Dujaili EAS. Effects of Pomegranate Extract on Inflammatory Markers and Cardiometabolic Risk Factors in Adults Aged 55–70 Years: A Randomised Controlled Parallel Trial. Nutrients. 2025; 17(7):1235.

Sens analyst Chris Stevenson on the atmosphere at SBP, hijinks at the end of Game 1, Dzone coverage and Ullmark, turning point of the game and Claude Giroux.

Episode Notes In this episode, DASON Clinical Pharmacist Liaison Dr. Angelina Davis chats with us about several articles about antibiotic prophylaxis for spontaneous bacterial peritonitis (SBP) in patients with cirrhosis. The materials reviewed in this episode can be found on the DASON Digest page on our website: https://dason.medicine.duke.edu/blog/sbp-prophylaxis-what-were-doing-why-were-doing-it-and-should-we-keep-doing-it For more information about DASON, please visit: https://dason.medicine.duke.edu/

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

This week on Stay By Plan, Afi and Zuu react to some of the most unhinged relationship stories the SBP team could find. From a husband who wants his wife to reschedule her birthday, to a guy who won't let his girlfriend chill with her friends alone, to a full-blown cheating confession—nothing is off-limits. Expect chaos, laughter, and hot takes (including Zuu's unforgettable quote: “If you're going to cheat, cheat well”

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Current fourth year students, Immy and Anya, share their experiences of working within the Placements Team in their role as Student Campus Partner (SCP), a paid internship with the University of Exeter. They discuss how they secured their roles, what they enjoy most about the position, and the benefits it offers students. SCP roles are available in other sections of the Career Zone and across the university.   The Student Campus Partnership (SCP) is exclusively for Exeter UK and international students who want to secure paid work on campus. The scheme promotes paid internships that are available across the university's campuses in Exeter and Penryn.   Useful Links: Find out more about Student Campus Partner (SCP) roles and sign up to the Student Internship Bulletin:  https://www.exeter.ac.uk/students/careers/internships/scp/ Find out more about Student Business Parnter (SBP) roles and sign up to the Student Internship Bulletin:  View current vacancies on  Handshake by searching for SCP or SBP in the job search. Sign up to a CV or Application form session via Handshake.

THE CASE Mrs P is aged 56 and has Type 2 Diabetes. Her HBA1c has reduced from 69 (8.5) to 58 (7.5) and her SBP has been reduced from 150 to 135. Her GP gets this discharge summary: Mrs P had surgery for a bowel obstruction caused by adhesions from a previous hysterectomy 5 years […]

In this episode, Uzair talks to Khurram Husain about the PML-N government's economic performance over the last year. We talked about how IMF stabilization is the easy part, why generating growth risks creating the same problems for the country, and the ways in which business interest groups are advocating for a return to past policies. Chapters: 0:00 Introduction 1:20 Performance review 8:10 Reasons for lack of reforms 20:30 Stabilization a big achievement? 29:40 SBP's role in killing inflation

Ines erzählt Euch alles wissenswerte zu diesem gar nicht mal so seltenen Krankheitsbild. Für mehr Infos schaut auch in den Artikel zu SBP auf unserer Homepage! Viel Spaß beim Hören! Der Beitrag „titriert“ Spontan bakterielle Peritonitis erschien zuerst auf pin-up-docs - don't panic.

Thanks for rocking with me for another year. Love you guys Support the show on Patreon & get access to a bunch of perks https://www.patreon.com/smallbrainedamerican This video, as well as every podcast on this channel is now available on Spotify. https://open.spotify.com/show/6twCOTAW3UmiJOmvm1bja1?si=c6b5c97b1c294334 My gear: DJI Action 4 https://amzn.to/3VOlhyx DJI Wireless Mics https://amzn.to/3xLkkze Insta 360 x3 https://amzn.to/45Ywdyj Follow the show ⬇️ Facebook https://www.facebook.com/realsmallbrainedamerican Instagram https://www.instagram.com/smallbrainedamerican/ Twitter https://x.com/SBAmerican_ Apple Podcasts https://podcasts.apple.com/us/podcast/small-brained-pod/id1724261259 Get Your Merch https://www.smallbrainedamerican.store SBA Year in Review 2024 | SBP #48

Hear Bill's interview with his longtime friend, Dr. Elmer Hall. Dr. Hall is president of Strategic Business Planning Company. SBP develops plans that every organization needs (tm): Start-ups, nonprofit, sustainability and patent commercialization.And now, rapid planning using Regenerative Dynamic AI.Dr. Hall has published several books and has been a professor of business (DBA & MBA) and Management Information Systems (MIS). Bill and Elmer have collaborated on several local commercial renewable energy projects and his experience is invaluable when it comes to business owners wishing to control their overhead by harvesting the sun's free energy. This was a great conversation, as Elmer shares information about one of the world's most powerful educational tools, Artificial Intelligence (AI). To learn more about how Dr. Hall can help your business or nonprofit, please give him a call:Elmer Hall  (954) 704-9100  SBP Support the show

JACC Associate Editor Theresa McDonagh, MBBCH  speaks with author Akshay S. Desai, MD, FACC about this paper on pulse pressure published in JACC and presented at AHA. In a pooled analysis of 16,950 patients with chronic HFmrEF or HFpEF enrolled from 4 global randomized clinical trials, a J-shaped relationship was observed between SBP and the risk of adverse CV events, with the lowest risk occurring at SBP values between 120 and 130 mmHg. A similar pattern was seen with PP, with the lowest risk found between 50 and 60 mmHg. Both higher SBP and higher PP independently predicted adverse CV events. Notably, PP remained a strong predictor of CV risk, independent of baseline SBP.

Welcome to the emDOCs.net podcast! Join us as we review our high-yield posts from our website emDOCs.net. Today on the emDOCs cast with Brit Long, MD (@long_brit), we cover the literature on evaluation and management of primary SBP. To continue to make this a worthwhile podcast for you to listen to, we appreciate any feedback and comments you may have for us. Please let us know!Subscribe to the podcast on one of the many platforms below:Apple iTunesSpotifyGoogle Play

Bitcoin mining has long been criticized for its energy consumption and carbon footprint. With growing concerns about the environmental impact of the Proof of Work process, the digital asset community has seen a heightened focus on finding ways for Bitcoin to align with the global sustainability goals of investors, corporations, and governments. The Sustainable Bitcoin Protocol (SBP) is an initiative that seeks to make Bitcoin mining more environmentally responsible by verifying and incentivizing the use of renewable energy sources. SBP aims to address this pressing issue by enabling miners to monetize their use of sustainable energy sources, thereby promoting green practices within the industry. Join Mark and the Sustainable Bitcoin Protocol team as they discuss topics such as the Sustainable Bitcoin Certificate, sustainability as an investable asset, and the future of clean energy development in digital assets. Remember To Stay Current! To learn more, visit us on the web at https://www.morgancreekcap.com/morgan-creek-digital. To speak to a team member or sign up for additional content, please email mcdigital@morgancreekcap.com

How many myths have you been told about Bitcoin's environmental impact? My special guest Elliot David from the Sustainable Bitcoin Protocol is on a mission to help the world understand the truth about the environmental benefits and myths of Bitcoin. Elliot debunks common misconceptions about Bitcoin's energy consumption and explains how SBP is pioneering transparency and sustainability in the Bitcoin network. We explore the innovative ways Bitcoin mining can drive the energy transition and support sustainable development, particularly in energy-poor regions. Elliot shares his journey from working in energy and climate sectors to integrating Bitcoin as a climate tech solution. We discuss the potential of Bitcoin mining to utilize stranded renewable energy and its role in electrifying remote communities. The conversation also touches on the challenges and opportunities of integrating Bitcoin with global energy systems and the importance of collaboration between Bitcoin advocates and the climate community. Tune in to discover how Bitcoin can be a force for good in the fight against climate change and energy poverty.

N Engl J Med 2007;356:1503-1516Background: By the turn of the 21st century more than 1 million coronary stent procedures were performed each year in the United States and approximately 85% were undertaken electively in patients with stable coronary artery disease. This pattern evolved without a single clinical trial demonstrating a concrete improvement in hard endpoints with percutaneous coronary intervention (PCI) compared to optimal medical therapy (OMT) alone. We have already reviewed several of these trials including ACME, RITA-2 and the Atorvastatin vs Angioplasty trial. Each trial was relatively small and none showed a significant benefit for revascularization compared to medical therapy on death or MI.Previous trials involving PCI compared to standard care or OMT included less than 3,000 patients altogether, did not broadly use intracoronary stents (instead using balloon angioplasty only) and they did not employ what would be considered a contemporary standard of medical management. Thus many questions involving the efficacy and safety of PCI versus OMT alone for managing stable CAD remained unanswered.The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial was designed to test the hypothesis that up front PCI plus OMT would significantly reduce the risk of death and nonfatal MI compared to OMT alone in patients with stable CAD.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: Eligible patients had stable CAD defined as either 1) a coronary stenosis of >/= 70% in one or more proximal epicardial coronary arteries and objective evidence of myocardial ischemia (based on the resting ECG or with exercise or pharmacologic vasodilator stress testing) or 2) a coronary stenosis of >/= 80% and classic angina without provocative testing. Patients were excluded if they had persistent Canadian Cardiovascular Society (CCS) class IV angina, a markedly positive stress test defined by substantial ST-segment depression or hypotensive response during stage 1 of the Bruce protocol), refractory heart failure or cardiogenic shock, an EF /=50% (4%).Patients in the trial were adherent with medical interventions and motivated to improve diet and lifestyle. For all patients, BP and cholesterol were improved and activity levels increased over the course of the study. For example, in the OMT group, baseline SBP and LDL were 130 mm Hg and 102 mg/dl at baseline and declined to 122 mm Hg and 72 mg/dl at 5 years, respectively. Similar reductions were seen in the PCI group. Fifty five percent of patients performed moderate physical activity at baseline and this increased to 77% at 5 years. Dietary adherence improved across the board and smoking decreased. Patients were followed for a median time of 4.6 years and 9% were lost to follow up with no significant difference between group. Overall, PCI + OMT did not reduce the primary endpoint of death or nonfatal MI compared to OMT alone (19.0% with PCI vs 18.5% with medical therapy; HR 1.05; 95% CI 0.87-1.27). Periprocedural MI was numerically more frequent in the PCI group whereas spontaneous MI was nearly identical between groups (statistics not provided). There were no statistically significant differences noted in any of the endpoints reported with the exception of revascularization during the follow up period, which occurred less frequently in the PCI group (20% vs 30%; p

Michael aka The Voice in the First Room has built community online that come and stay for his unique voice. While on a trip to his native country Ghana, Michael stopped by SBP to sit with Afi and Zuu and talk about everything from his recent success and his creative processes to his adoring fans! Follow ​⁠  @michaeleok_  : https://www.instagram.com/michaeleok https://www.tiktok.com/@michaeleok Listen to the full audio: Spotify: https://spoti.fi/46UrLkx Apple Podcasts: https://apple.co/4dsT9sD Visit Stay by Plan: https://www.staybyplanpod.com Don't forget to share, rate, follow and subscribe to the podcast! Follow us! Instagram: https://www.instagram.com/staybyplanpod Twitter: https://www.x.com/staybyplanpod TikTok: https://www.tiktok.com/@staybyplanpod Subscribe to our YouTube channel: https://www.youtube.com/c/staybyplanpod Share your thoughts with #StayByPlan! Photography by Ellis Trace https://www.instagram.com/spotlightimaging Motion Graphics by Eugene https://www.instagram.com/eugenegyasi_ Intro song produced by: Lil Kwaw

My guest this week is Eric Danetz. He's the president and founder of Spencer Grace Advisors, a consultancy helping organizations navigate change and achieve growth. Previously, he was the Global Chief Revenue Officer at Reuters, overseeing global sales and customer success. He's also served as the Chief Business Officer at AccuWeather and SBP, and GM at Time Inc. International, where he managed a portfolio of 90 brands in 170 countries. He's held executive roles at Fortune, Money, Alloy Digital, Newsweek, Daily Beast, CBS Interactive, CNET, and more. He's been a board member for the IAB Video, Bite the Block, and Silicon Alley Sports. Finally, he's a proud father of two, one of whom I just learned is a new driver—congratulations! He's an avid traveler, animal lover, and racket sports enthusiast. 

I read the $1,000.00 example that you write and 50% of 1K is 500.00 a month for my wife. That makes sense and I understand. My Q is my spouse is 12 yrs YOUNGER than I am. Does the Age difference make a difference in the SBP cost? - Albert 

Contributor: Aaron Lessen MD Educational Pearls: A recent study assessed EMS treatment of high blood pressure in the field 2404 patients randomized to prehospital treatment (1205)  vs. usual care (1199) Included patients with prehospital BP greater than 150 mm Hg The treatment arm's BP goal was 130-140 mm Hg The primary efficacy outcome was functional status 90 days out Stroke was confirmed by imaging upon hospital arrival On arrival, the mean SBP of the treatment arm was 159 mm Hg compared with 170 mm Hg in the usual care group No significant difference in functional outcomes between the treatment group and the usual care group (Common Odds Ratio of 1.00, 95% CI = 0.87-1.15) Post-imaging analysis revealed 46.5% of the undifferentiated patients had a hemorrhagic stroke Prehospital reduction in BP did reduce the odds of poor functional outcome in hemorrhagic stroke patients alone (Common Odds Ratio 0.75, 95% CI 0.60-0.92) Those with ischemic stroke had increased odds of poor functional outcome (Common Odds Ratio 1.30, 95% CI 1.06-1.60) Bottom line: it is challenging to identify the stroke type in the prehospital setting and therefore not necessarily helpful to treat the blood pressure References 1. Ren X, Zhang C, Xu P, et al. Intensive Ambulance-Delivered Blood- Pressure Reduction in Hyperacute Stroke. New England Journal of Medicine. 2024;390(20):1862-1872. doi:10.1056/NEJMoa2314741 Summarized by Jorge Chalit, OMSIII | Edited by Meg Joyce & Jorge Chalit  

In this episode: survivor benefit plans, VA benefits, VSO's disability benefits, tax planning, healthcare, and blended retirement systems. This week we are joined by Daniel Kopp, founder of Wise Stewardship Financial Planning, to outline ways you can best prepare for military retirement. Together we cover pensions, navigating the Survivor Benefit Plan and additional benefits, healthcare and disability resources, as well as other financial decisions you can consider as you begin to transition out of the military. When dealing with any kind of retirement planning, taking actionable steps to prepare and get a plan in place for you and your family is essential. While everyone's circumstances may be different as they transition out of the military, there are many resources available and benefit programs you are entitled to before and after you leave duty! Daniel Kopp, CFP Website: wisestewardshipfp.com Podcast: Military to Financial Planner Timestamps: 1:26 – Introduction 2:32 – Approaching Military Retirement/Blended Retirement System 9:38 – Military Benefits/Healthcare 15:36 – VA Benefits/Term Life Insurance 22:12 – Disability Benefits/VSO's 30:17 – Survivor Benefit Plans 43:13 – SBP Contingencies and Child Coverage 50:41 – Tax Planning 56:26 – Conclusion Resources Mentioned In Today's Episode: Blended Retirement VA education benefits for survivors and dependents Everything About The Military's Survivor Benefit Plan SBP Financial Analysis Tools Daniel Kopp Estate Planning for Military Families | Military Money Manual Podcast Episode 83 Accredited VSO Representatives Transition Planning from a Military Career on the Path to FI | ChooseFI Ep 296 “Military in Transition's Guide to The Survivor Benefit Plan: Navigating the SBP” by Forrest Baumhover How VA Disability Compensation Affects Military Retirement Pay Income Tax and Rental Properties When You're in the Military MFAA ChooseFI US Military Subscribe to The FI Weekly! More Helpful Links and FI Resources: Top 10 Recommended Travel Rewards Credit Cards Empower: Free Dashboard to Track Your Finances CIT Bank Platinum Savings Account M1 Finance: Commission-Free Investing, 1-click rebalancing CashFreely: Maximize Your Cash Back Rewards Travel Freely: Track all your rewards cards and points Emergency Binder: For Your Family's Essential Info (code ‘CHOOSEFI' for 20% off) Student Loan Planner: Custom Consult (with $100 Discount) Get a cheaper phone plan with Mint Mobile

Contributor: Travis Barlock MD Educational Pearls: There are three indications for IV albumin in the ED Spontaneous bacterial peritonitis (SBP) Patients with SBP develop renal failure from volume depletion Albumin repletes volume stores and reduces renal impairment Albumin binds inflammatory cytokines and expands plasma volume Reduced all-cause mortality if IV albumin is given with antibiotics Hepatorenal syndrome Cirrhosis of the liver causes the release of endogenous vasodilators The renin-angiotensin-aldosterone system (RAAS) fails systemically but maintains vasoconstriction at the kidneys, leading to decreased renal perfusion IV albumin expands plasma volume and prevents failure of the RAAS Large volume paracentesis Large-volume removal may lead to circulatory dysfunction IV albumin is associated with a reduced risk of paracentesis-associated circulatory dysfunction There are many other FDA-approved conditions for which to use exogenous albumin but the data are conflicted about the benefits on mortality References 1. Arroyo V, Fernandez J. Pathophysiological basis of albumin use in cirrhosis. Ann Hepatol. 2011;10(SUPPL. 1):S6-S14. doi:10.1016/s1665-2681(19)31600-x 2. Bai Z, Wang L, Wang R, et al. Use of human albumin infusion in cirrhotic patients: a systematic review and meta-analysis of randomized controlled trials. Hepatol Int. 2022;16(6):1468-1483. doi:10.1007/s12072-022-10374-z 3. Batool S, Waheed MD, Vuthaluru K, et al. Efficacy of Intravenous Albumin for Spontaneous Bacterial Peritonitis Infection Among Patients With Cirrhosis: A Meta-Analysis of Randomized Control Trials. Cureus. 2022;14(12). doi:10.7759/cureus.33124 4. Kwok CS, Krupa L, Mahtani A, et al. Albumin reduces paracentesis-induced circulatory dysfunction and reduces death and renal impairment among patients with cirrhosis and infection: A systematic review and meta-analysis. Biomed Res Int. 2013;2013. doi:10.1155/2013/295153 5. Sort P, Navasa M, Arroyo V, et al. Effect of Intravenous Albumin on Renal Impairment and Mortality in Patients with Cirrhosis and Spontaneous Bacterial Peritonitis. N Engl J Med. 1999;341(6):403-409. Summarized by Jorge Chalit, OMSII | Edited by Meg Joyce & Jorge Chalit  

In this study, the authors first sought to empirically derive centiles for heart rate (HR), respiratory rate (RR), and systolic blood pressure (SBP) for adults with out-of-hospital emergencies who were transported to an ED. Second, they aimed to evaluate the impact of adjusting for age in the evaluation of centile curves for vital signs to identify practical targets for adjustment of vital signs classification in adult patients based on age categories. Third, they examined the association of both unadjusted and age-adjusted vital signs with hospital admission and in-hospital mortality.

On this episode of the Lesson Learned for Vets podcast, we welcome Todd Nelson. Although not a veteran himself, he has dedicated his career to helping service members navigate their finances as a financial advisor for Edward Jones. There are often unique financial challenges that accompany transitioning service members into their next career. Todd is the host of Transition 30, a network that uses quarterly Zoom calls to connect service members to resources and organizations that support the military transition process.Todd lays out 3 considerations every service member must make as they exit the military. 1) How much money do I need to replace? 2) How much money do I want and how much money do I need? 3) How am I going to get from what I need to what I want? Having mentors and talking to subject matter experts in taxation can become a valuable piece of establishing your financial foundation. The first consideration when thinking about SGLI to VGLI is knowing what your needs are when it comes to insurance. Speak to your spouse, significant other and family members before you start the VA disability process. During the VA process, everything is documented. If you start your insurance research after you have already started the VA process, there may be some exclusions to your policy because of the VA documentation. The second consideration is realizing that VGLI is there for a reason. Sometimes private life insurance companies won't cover you because of your service-related injuries. When it comes to the Survivor Benefit Plan (SBP), it's important to realize that it's a personal decision that should be based off several factors. Research the SBP at militarypay.defense.gov prior to out-processing. During out-processing, you will be asked if you want to opt out of SBP because by default, you are opted into the plan. An alternative to SBP is life insurance. Another priority when transitioning from the military is knowing how your tax bracket will be influenced. Your pension and new job will affect your tax bracket. Start setting money aside for this reality. VA disability payments are tax free. It is a benefit that you have earned and can be viewed as a lifetime annuity. You are guaranteed that income with a cost-of-living adjustment each year. With just a 10% disability rating, you are eligible for a VA home loan. Service members who are separating and plan to file for disability compensation can file their claim before separation through the Benefits Delivery at Discharge (BDD) program. The BDD program allows service members to apply for VA disability compensation benefits between 180 to 90 days prior to separation. If your disability rating is 30% or higher, you will have preference when it comes to jobs in the federal government. There are many considerations when it comes to accepting a job offer. Look at the total compensation package, not just the salary. Benefits might include a 401K or a 403b and stock options. You will want to consider starting a Roth IRA or a traditional IRA. Do your research and seek assistance and advice to help you navigate your financial situation.Subscribe to our YouTube channel at https://tinyurl.com/llforvets22Connect with Todd at https://www.linkedin.com/in/todd-nelson-edward-jones/Transition 30 LinkedIn Group: AAFMA, the American Armed Forces Mutual Aid Association is the longest-standing nonprofit association offering life insurance, wealth management, mortgages, survivor assistance and more. AAFMA is dedicated to helping servicemembers be ready for life after the military. AAFMAA would like to offer you their free Transition Timeline, a guide to help you create a solid military transition plan. Let AAFMAA help you get ready for your next step by visiting www.aafmaa.com/ll4v.

Lancet 2005;366:1622-32Background Beta blockers were routinely used for the early management of patients with AMI; however, their efficacy and safety remained uncertain in this clinical scenario. Recall that in the BHAT trial, propranolol reduced death 2 years following an AMI with an NNT of approximately 33 but the cohort was highly selected, the drug was started, on average, 14 days following admission and those over the age of 70 were excluded. ISIS-1 found that atenolol reduced death with an NNT of approximately 100 when started immediately in lower risk AMI patients but treatment effect heterogeneity was observed in patient subgroups with higher risk features. The ClOpidogrel and Metoprolol Infarction Trial (COMMIT) sought to test the hypothesis that early beta-blockade with metoprolol would reduce cardiac events and death in a broad population of patients with 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.Patients Patients with suspected myocardial infarction, who presented with ST elevation, left-bundle branch block, or ST depression within 24 hours of symptom onset were eligible. Patient eligibility was ultimately determined by the responsible physician but protocol guidance suggested the following relative contraindications: persistently low blood pressure (SBP

On this episode from our archive, originally posted on March 15, 2022, The Curious Clinicians examine why cirrhosis predisposes to SBP, and why bacterial translocation across the bowel wall into ascites doesn't actually occur! Read the show notes here. Click here to obtain AMA PRA Category 1 Credits™ (0.5 hours), Non-Physician Attendance (0.5 hours), or ABIM MOC Part 2 (0.5 hours). Audio edited by Clair Morgan of nodderly.com. This episode is sponsored by Audible! New members can try Audible free for 30 days using our own Curious Clinicians podcast code - visit Audible.com/TCCPOD or text TCCPOD to 500-500. 

Lancet 2001;357:1385-90.Background While beta blockers were frequently used in patients with acute myocardial infarction complicated by heart failure, at the time the CAPRICORN trial was undertaken, supportive evidence from contemporary, large scale randomized trials was lacking. The BHAT and ISIS-1 trials, reviewed in this section, were published in 1982 and 1986, respectively; before contemporary therapies like thrombolysis/revascularization and ACE-inhibition had been established. These early trials also excluded patients with overt heart failure or those who had concerning signals, such as soft hemodynamics. The CAPRICORN trial sought to test the hypothesis that early initiation of carvedilol in patients with AMI complicated by heart failure and LV dysfunction would reduce morbidity and mortality compared to placebo.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 Eligible patients were 18 years or older with a stable, definite myocardial infarction occurring 3-21 days prior to randomization with either a left ventricular ejection fraction of ≤40% or a wall motion index score of ≤1.3 and who were receiving an ACE inhibitor for at least 48 hr and were on a stable dose for at least 24 hr. Patients could have received IV diuretics during the acute phase but were excluded if they continued to require IV diuretics or inotropes or had uncontrolled heart failure. Other reasons for exclusion included unstable angina, SBP 80 mmHg, the dose was increased to the next level. The patient remained in the outpatient department for 2hr to ensure that no side effects ensued.During the maintenance period patients were reviewed every 3 months during the first year and every 4 months thereafter. Investigators were encouraged to review the dose of study medication at every visit and to ensure that doses of other drugs, especially ACE inhibitors, were adjusted accordingly to achieve optimum dose levels.Endpoints The original primary endpoint was all-cause mortality and the trial was intended to run until a total of 633 primary endpoint events occurred. However, during a masked analysis the data and safety monitoring committee noted that overall mortality was lower than predicted and that the study could not be completed with the original sample size and power as planned. The steering committee, therefore, designated co-primary endpoints. The first was a new composite primary endpoint of all-cause mortality or cardiovascular hospital admission and the second was all-cause mortality. The trial was still intended to run until 633 primary endpoint events occurred with the original sample size. The alpha (false-positive) was divided between the 2 primary endpoints so that the composite endpoint of all-cause mortality and cardiovascular hospitalization was tested at 0.045 and all-cause mortality was tested at 0.005. Secondary endpoints included sudden death, hospitalization for heart failure, recurrent nonfatal MI, and all-cause mortality or nonfatal MI.Results 1,959 patients were included in the final analysis; 984 in the placebo group and 975 in the carvedilol group. The mean follow-up was 1.3 years. Compared to placebo, carvedilol did not significantly reduce the composite primary endpoint of all-cause death or cardiovascular hospitalization (HR 0.92; 35% vs 37%; 95% CI 0.80-1.07) or all-cause death alone (HR 0.77; 12% vs 15%; 95% CI 0.6-0.98). The authors present the all-cause mortality result as positive; however, it is NOT. In table 1, the p for all-cause mortality is 0.031, which is >0.005. Thus, there is a good chance that the mortality result represents a false positive finding.For the secondary endpoints, there were reductions in nonfatal MI and the combined endpoint of all-cause death or nonfatal MI for patients in the carvedilol group but these results are based on a relatively small number of events.Of the 940 patients who entered the maintenance phase in the carvedilol group, 74% reached the maximum dose of 25 mg bid while 11% and 7% reached 12.5 mg bid and 6.25 mg bid.There is no subgroup data or safety data presented in the main paper.   Conclusions In patients with AMI complicated by heart failure and significant LV dysfunction, carvedilol did not significantly reduce all-cause death or cardiovascular hospitalizations compared to placebo. This trial is often presented and discussed as a positive trial but it is not. The appropriately powered endpoint in this case was the composite primary endpoint, which was clearly negative. The difference in all-cause mortality is based on a small number of events with a post-hoc power of 19.3% at the prespecified alpha of 0.005. The reported p-value for all-cause mortality was 0.031, which was much higher than the prespecified p value of ≤ 0.005 to declare a positive result. Due to the underpowered nature of all-cause death, the investigators chose to make the alpha as low as it was to avoid making false positive claims but then they did so anyway!While power is generally taught to infer a trial's strength to avoid false negative results, low power also increases a trial's susceptibility to false positive results. We have discussed this with small trials involving magnesium and nitrates, which were highlighted by the meta-analyses presented in the ISIS 4 publication.In conclusion, CAPRICORN was a negative trial. Its primary results were negative and differences in secondary endpoints, including the reduction in death, should be viewed as “hypothesis generating” only. It does not clearly establish a beneficial role for beta blockers in post-MI patients with significant LV dysfunction and heart failure.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

Did you know research shows that a person who sets (and achieves) goals tends to have higher motivation, higher self-esteem and a greater sense of self-confidence and autonomy? Setting an achievable goal also gives a boost to your systolic blood pressure (SBP). However, it wouldn't surprise me if, as a highly sensitive, your experience with goal setting has been quite different. Here's why: setting goals rooted in comparison or based on what you think you "should be" doing actually lowers your blood pressure. Which slows you down, and has you feel like you're trudging through mud - with no motivation to actually take the actions needed to accomplish the goal. “We are the balance to the other 80 percent.” - Heather Dominick. Learn more about this episode of Business Miracles at https://www.businessmiracles.com/178

Background: Massive pulmonary embolism  defined as sustained hypotension (SBP

Lancet 1995;345:669-685.Background The premises for ISIS-4 were similar to GISSI-3 with the notable exception of adding an arm to test the effect of magnesium in acute myocardial infarction. Up to this point magnesium was commonly used in patients with acute MI. It was suspected to limit infarct size and reduce arrhythmic events and death; however, it was backed only by animal experiments and small trials in humans that were underpowered to test for realistic differences in mortality. A meta-analysis of such trials was cited in the ISIS-4 manuscript, which reported a 50% relative reduction in mortality! You read that correctly. ISIS-4 was undertaken to test 3 distinct hypotheses: that 1 month of Captopril , 1 month of isosorbide mononitrate, and 24 hours of intravenous magnesium reduced mortality in patients presenting with definite or suspected 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.Patients Patients were eligible if they were thought to be within 24 hours of the onset of symptoms of suspected or definite AMI (with or without ECG changes) and if they had no definite contraindications to any of the study treatments. Contraindications were not specified by protocol but by the responsible physician but standard contraindications were suggested like conditions associated with a high risk of adverse events like cardiogenic shock or persistent hypotension (SBP 70 years of age who did not benefit despite their significant numbers and contribution to events in the trial. These results are in contrast to GISSI-3, which prespecified a subgroup analysis in elderly patients and found a statistically significant reduction in the primary combined endpoint and reduction in the rates of death (no statistics provided).In the discussion of ISIS-4 the authors provide results from a meta-analysis involving 15 trials of ACE inhibitors on short-term mortality when started early in AMI. This includes 11 small trials, and 4 larger trials; GISSI-3 and ISIS-4 are the largest and presented in this section; CONSENSUS-II and CCS-1 were smaller but still provide important data. All combined, early ACE inhibition reduced short-term mortality and the margin was very similar to that found in ISIS-4 and GISSI-3 (7.27% vs 7.73%; p=0.006).The ISIS-4 trial did not demonstrate a benefit for isosorbide mononitrate. Again, in the discussion, the authors provide results from a meta-analysis involving 22 trials, including 20 small trials as well as GISSI-3 and ISIS-4. When all results are combined, a statistically significant reduction in death is found for nitrates; however, significant treatment effect heterogeneity is demonstrated between the small trials and GISSI-3 and ISIS-4, which eliminates any confidence in the overall result. This demonstrates the importance of basing clinical translation on large trials, appropriately powered to detect differences in the endpoints of interest; otherwise, there is a good chance of being fooled by false positive findings.Finally, ISIS-4 conclusively shattered all delusions related to the efficacy of magnesium in AMI and effectively represented a reversal in standard practice. The authors present a meta-analysis involving 9 small trials, a larger but still underpowered trial called LIMIT-2, and ISIS-4. Extreme heterogeneity is identified between small and large studies and the treatment effect goes from a very large benefit in small studies to a likely small harm in the one appropriately powered trial.The story of magnesium in AMI is an excellent demonstration of positive outcome bias in medical research. It highlights how the published literature, especially for small, underpowered studies is more likely to contain studies reporting positive treatment effects but these should not be trusted. Multiple mechanisms for positive outcome bias exist including reporting bias on the part of investigators (i.e., the “file drawer effect”) and biases on the part of journal reviewers and editors to accept and publish positive studies compared to those that report negative findings.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

Lancet 1994;343:1115-22.Background By the time GISSI-3 was undertaken, evidence had emerged suggesting afterload reduction with angiotensin-converting-enzyme (ACE) inhibitors improved morbidity and mortality in patients with chronic systolic heart failure and these agents were already an established treatment for acute, severe heart failure based on theoretical grounds, despite lack of evidence from large scale RCTs. There was also lower level evidence that nitrates reduced mortality in patients with acute MI and these drugs were broadly used in coronary care units at the time. The GISSI-3 trial was undertaken to test the hypotheses that 6 weeks of treatment with lisinopril alone or transdermal glyceryl trinitrate (GTN) alone reduced the combined endpoint of mortality and severe LV dysfunction at 6 weeks compared to controls.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 were eligible if they presented with chest pain and ST segment elevations of ≥1 mm in any limb lead of the electrocardiogram and/or ≥2 mm in any precordial leads and were admitted to the cardiac intensive care unit (CCU) within 24 hr from the onset of symptoms. Absolute contraindications included: severe heart failure requiring any of the study treatments, Killip class 4, high risk of hemodynamic deterioration after treatment with vasodilators (SBP 70 years of age (41% of excluded vs 27% of enrolled). As expected, excluded patients had higher in-hospital mortality (12% of excluded vs 6% of enrolled).Seventy-eight percent of patients enrolled were men and nearly three quarters were under the age of 70. Patients with anterior STEMI accounted for approximately 27%, those with inferior 32% and non-Q-wave MI's approximately 19%. Time from symptom onset was between 12-24 hours in 40%, between 6-12 hours in 25% and less than 6 hours in 35%. The vast majority of patients had a Killip score of 1 (85%) with the remainder having a Killip score of 2 (14%). Procedures The study used a 2x2 factorial design, resulting in 4 treatment groups: lisinopril alone, transdermal GTN alone, combination therapy with lisinopril and transdermal GTN, or no trial therapy.Patients randomized to oral lisinopril received 5 mg at the time of randomization, followed by 5 mg 24 hours later and 10 mg 48 hours later to be continued at a dose of 10 mg daily for 6 weeks. Patients with SBP 70 years of age, lisinopril significantly decreased the combined endpoint (OR 0.83; 24.8% vs 28.3%; 95% CI 0.74-0.94) and death (14.0% vs 15.6%). Odds ratios were not provided on individual components of the endpoints in pre-specified subgroup analyses. In women, lisinopril significantly decreased the combined endpoint (OR 0.86; 20.8% vs 23.4%; 95% CI 0.74-0.99) and death (10.7% vs 12.9%). Adverse event outcomes are not provided for these subgroups.Unlike lisinopril, transdermal GTN did not significantly reduce the combined endpoint (OR 0.94; 15.9% vs 16.7%; 95% CI 0.87-1.02) or death (OR 0.94; 6.5% vs 6.9%; 95% CI 0.84-1.05). There were no significant differences in any other clinical events. In pre-specified subgroup analyses, transdermal GTN did not significantly reduce the combined endpoint; however, absolute differences in death were very close to those seen with lisinopril.Additional results from this trial can be gleaned from analyses of patients based on whether they were in 1 of 4 treatment groups based on the factorial design 1) lisinopril + GTN control, 2) GTN + lisinopril control, 3) lisinopril control + GTN control (i.e., double control), or 4) lisinopril + GTN (i.e., double treatment); however, caution was urged in interpreting these underpowered comparisons that included sample sizes half as large as the primary comparison groups.Compared to double controls, neither lisinopril alone or GTN alone significantly reduced the combined endpoint or death but the absolute differences in events mirrored the primary analyses; however, the combination of lisinopril and GTN significantly reduced both the combined endpoint (OR 0.85; 14.8% vs 17.0%; 95% CI 0.76-0.94) and death (0.83; 6.0% vs 7.2%; 95% CI 0.70-0.97). These treatment effects were slightly larger than those for lisinopril alone.Conclusions GISSI-3 is the first trial to show that immediate treatment with ACE inhibition can reduce death and severe LV dysfunction in patients with acute myocardial infarction and this benefit is maintained in women and elderly patients who are at higher risk for experiencing adverse events. The NNT for the combined endpoint and death at 6 weeks was 71 and 125, respectively. The NNTs to prevent these outcomes in women and elderly patients were considerably lower (e.g., relative risk reductions were preserved resulting in higher absolute treatment benefits). The same effect was not observed for transdermal GTN; however, there was some hint from the trial that GTN may have a synergistic effect when used in combination with lisinopril.It must be pointed out that, like the earlier beta blocker trials, patients in GISSI-3 were hemodynamically stable and severe heart failure was an absolute contraindication. Thus, this trial does not say anything about the efficacy of ACE inhibition or nitrate therapy for patients with acute myocardial infarction complicated by acute heart failure and/or hemodynamic instability. Yet both treatments were frequently used for severe heart failure based on pathophysiologic reasoning at the time (e.g., effects of reducing preload and afterload on congestion and cardiac performance).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

Lancet 1992;339:753-770.Background Results from the GISSI and ISIS-2 trials demonstrated a clear benefit for the early opening of acutely blocked arteries with fibrinolytic treatment in patients presenting with STEMIs. ISIS-2 also demonstrated the benefit of aspirin in the acute and subacute phases of MI. However, after opening a blocked artery, concern for re-occlusion persisted, especially in the first several days to week, and experts postulated that antithrombotic therapy with heparin could improve outcomes compared to use of aspirin alone. The 3rd study from the ISIS group sought to test the hypothesis that therapeutic heparin plus aspirin reduced mortality compared to aspirin alone in patients treated with early fibrinolytic therapy. The investigators also sought to test whether different fibrinolytic regimens were safer and more effective compared to each other. *Since treatment with fibrinolytic therapy is no longer standard practice in most places and no significant differences in fibrinolytic regimens were ultimately reported, we will focus only on the heparin plus aspirin versus aspirin alone portion of the study.Patients Patients were eligible for ISIS 3 if they were thought to be within 24 hours of the onset of symptoms of suspected or definite acute MI (with or without ECG changes) and if they had no definite contraindications to fibrinolytic therapy. Contraindications were not specified by protocol but by the responsible physician; standard contraindications to fibrinolysis were suggested. Patients were eligible even if aspirin or heparin was thought to be clearly contraindicated or if it was thought that aspirin alone was not enough (i.e., that some anticoagulant was clearly indicated). In such cases, patients were still to be randomized and the allocated antithrombotic regimen was then modified as thought appropriate for the particular patient.Baseline characteristics The majority of patients were men (73%) and under the age of 70 years who presented within 6 hours from the onset of pain (78%). Enrolled patients appeared to be generally stable as only 6% had SBP

Lancet 1990;336:65-71.Background Large trials up to this point had established the role of thrombolytic therapy and aspirin in patients with acute MI. The next question centered on the different types of thrombolytic agents as well as the merits of adding high dose heparin to aspirin following revascularization. Data from smaller studies showed that alteplase (tPA) had a higher recanalization rate at 90 minutes compared to streptokinase (SK). “Recanalization” is a surrogate endpoint – a person doesn't necessarily care whether their artery is open or not at 90 minutes, but instead, whether they live or die, and how they live in the aftermath of a heart attack. The GISSI-2 trial sought to test the hypothesis that tPA would reduce the composite hard endpoint of mortality and extensive LV dysfunction compared to streptokinase (SK) and that heparin plus aspirin compared to aspirin alone would do the same.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 were eligible who presented with chest pain and ST segment elevations of ≥1 mm in any limb lead of the ECG and/or ≥2 mm in any precordial leads and were admitted to the CCU within 6 hr from the onset of symptoms. Absolute contraindications included: recent or current bleeding, stroke within the previous 6 months, a surgical or invasive procedure or trauma within the previous 2 weeks, uncontrolled hypertension defined as SBP ≥200 mmHg or DBP ≥110 mmHg, or previous treatment with SK within 6 months.Baseline characteristics The number of patients who were admitted to CCUs with acute myocardial infarctions (MI) over the study period was 38,086 and 12,490 (33%) were ultimately enrolled. Reasons for exclusion included: more than 6 hr from onset of symptoms (61%), contraindications to fibrinolysis (15%), unlikely to have acute MI (13%), administrative reasons (5%), ST depressions (4%) and 1% were not reported. Similar to GISSI-1, which also provided information on patients enrolled versus those who were not, women were more likely to be excluded (30% of excluded vs 20% of enrolled) as were patients >70 years of age (41% of excluded vs 22% of enrolled). The death rate of those excluded was higher (11% of excluded vs 9% of enrolled).Approximately 80% of patients enrolled were men under the age of 70. Patients with inferior (34%) and anterior STEMI's (31%) composed more than half of the cohort. 72% of patients presented within 3 hours of symptom onset and over 95% had Killip scores of II or below with the vast majority being Killip I (78%).Procedures Immediately following randomization half of all patients received either 1.5 MU of SK infused over 1 hour or 100 mg of tPA infused over 3 hours. Since this was a 2x2 factorial design, half of all patients also received 12,500 U of subcutaneous heparin twice daily starting 12 hours after the beginning of the tPA or SK infusion and to be continued until hospital discharge.All patients without specific contraindications were recommended to receive oral aspirin 325 mg/day and 5-10 mg of IV atenolol, even before randomization, as soon as evolving MI was diagnosed.Endpoints The combined primary endpoint consisted of all-cause mortality plus the number of patients who had late (day 4 or later) clinical congestive heart failure, or extensive LV damage (LVEF

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

Lancet 1986;397-401Background This study by the Italian Group for the Study of Streptokinase in Myocardial Infarction (GISSI) is the first large trial to test the hypothesis that opening blocked heart arteries, in this case via use of the intravenous thrombolytic agent Streptokinase, reduces death in patients presenting with acute myocardial infarction (MI). Opening blocked arteries or revascularization is now a foundational element of cardiovascular medicine that arguably spurred much of the growth in the field over the 1990's and early 2000's. Therefore, it is critical to revisit this historic trial and appreciate the lessons it taught us.Patients Patients were eligible who presented with chest pain and ST segment elevations of ≥1 mm in any limb lead of the electrocardiogram and/or ≥2 mm in any precordial leads and were admitted to the cardiac intensive care unit (CCU) within 12 hours from the onset of symptoms. Absolute contraindications included recent or current bleeding, stroke within the previous 2 months, a surgical procedure or trauma within the previous 10 days, invasive procedures within the previous 10 days, SBP ≥200 mmHg, DBP ≥110 mmHg, previous treatment with streptokinase, or any other life-threatening condition.Baseline characteristics The number of patients who were admitted to CCUs with acute MIs over the study period was 31,826 and 11,806 (37%) were ultimately enrolled. Reasons for exclusion included being more than 12 hr from onset of symptoms (51%), contraindications to Streptokinase (21%), unlikely to have acute MI (19%), administrative reasons (8%) and 2% were not reported. Notably, women were more likely to be excluded (27% of excluded vs 20% of enrolled) as were patients >75 years of age (21% of excluded vs 11% of enrolled).Not a lot of demographic information is provided on the cohort in the main manuscript but it was composed primarily of men (80%) who were ≤65 years of age (65%). Only a small percentage of patients were unstable, as evidenced by SBP ≤90 mmHg (

Mamileiros e mamiletes, está no ar a nossa retrospectiva! Nesse programa, pra fazer aquele resumão com os principais fatos e acontecimentos de 2023, convidamos: Thomas Traumann, João Paulo Charleaux, Denize Ornelas, Cinthia Leone, Roberta Nina, Cris de Luca, Samuel Pessôa e Sarah Oliveira. O Mamilos continua na estrada há 9 anos porque você é nosso ouvinte. Toda semana você reserva mais de uma hora da sua semana para nos ouvir. Há 9 anos, o Mamilos continua no ranking dos mais ouvidos do Spotify e Apple e é isso que nos incentiva a continuar a produzir os programas. Obrigada por tanto! Agradecemos também todas as marcas que anunciaram no Mamilos esse ano e ajudam a viabilizar que nosso conteúdo seja disponibilizado de graça para os ouvintes. Feliz ano novo! Nos vemos em 2024! _____ SBP Quem tem bebê ou criança em casa, sabe como é agoniante ver eles acordarem de manhã cheios de picadas de pernilongos, né? SBP Repelente Elétrico Líquido Cheiro Suave torna as noites de sono bem mais tranquilas e livres de mosquitos. Fora que tem um cheiro mais suave em comparação com a versão regular e pode ser usado em ambientes com bebês a partir de 6 meses. Mas tem que usar do jeito certo pra funcionar direitinho: tem que pôr na tomada e deixar uma fresta da janela ou da porta aberta, pros mosquitos poderem sair! Não adianta por no quarto e deixar tudo fechado, porque os pernilongos vão continuar presos lá dentro. E tem que deixar a pelo menos 2 metros da cabeceira da cama. Dessa forma o SBP Repelente Elétrico Líquido Cheiro Suave mantém afastados do ambiente pernilongos e mosquitos, incluindo os transmissores da dengue. Amar é proteger, e proteger é SBP. Saiba mais em: sbpprotege.com.br _____ FALE CONOSCO . Email: mamilos@mamilos.me _____ CONTRIBUA COM O MAMILOS Quem apoia o Mamilos ajuda a manter o podcast no ar e ainda participa do nosso grupo especial no Telegram. É só R$9,90 por mês! Quem assina não abre mão. https://www.catarse.me/mamilos Equipe Mamilos _____ Mamilos é uma produção do B9 A apresentação é de Cris Bartis e Ju Wallauer. Pra ouvir todos episódios, assine nosso feed ou acesse mamilos.b9.com.br Quem coordenou essa produção foi Beatriz Souza. A edição foi de Mariana Leão e as trilhas sonoras, de Angie Lopez. A coordenação digital é feita por Agê Barros. O B9 tem direção executiva de Cris Bartis, Ju Wallauer e Carlos Merigo. O atendimento e negócios é feito por Telma Zennaro.

Mamileiros e mamiletes, tem alguém aí que não tá no clima do natal? Shopping lotado, papai noel pra tudo quanto é lado, trânsito pra tudo. Função infinita pra organizar a ceia de natal, correria pra terminar todas as tarefas do trabalho antes do recesso. Absolutamente tudo fica mais cheio, mais caro ou mais barulhento. Sem falar nas mesmas brigas de todo ano: panetone x chocotone, adoradores e haters de passas no arroz. E aqueles papos chatos com familiares que tão mais pra conhecidos que só vemos de vez em nunca? Se você também não tá super no clima do Natal esse ano, tá tudo bem, vem com a gente que o programa de hoje é pra liberar o Grinch sem julgamentos. Pra liberar o Grinch com a gente, convidamos Flavia Penido, Clarissa Borges e Mari Muradas. Dá o play e vem com a gente! _____ SBP Quem tem bebê ou criança em casa, sabe como é agoniante ver eles acordarem de manhã cheios de picadas de pernilongos, né? SBP Repelente Elétrico Líquido Cheiro Suave torna as noites de sono bem mais tranquilas e livres de mosquitos. Fora que tem um cheiro mais suave em comparação com a versão regular e pode ser usado em ambientes com bebês a partir de 6 meses. Mas tem que usar do jeito certo pra funcionar direitinho: tem que pôr na tomada e deixar uma fresta da janela ou da porta aberta, pros mosquitos poderem sair! Não adianta por no quarto e deixar tudo fechado, porque os pernilongos vão continuar presos lá dentro. E tem que deixar a pelo menos 2 metros da cabeceira da cama. Dessa forma o SBP Repelente Elétrico Líquido Cheiro Suave mantém afastados do ambiente pernilongos e mosquitos, incluindo os transmissores da dengue. Amar é proteger, e proteger é SBP. Saiba mais em: sbpprotege.com.br _____ FALE CONOSCO . Email: mamilos@mamilos.me _____ CONTRIBUA COM O MAMILOS Quem apoia o Mamilos ajuda a manter o podcast no ar e ainda participa do nosso grupo especial no Telegram. É só R$9,90 por mês! Quem assina não abre mão. https://www.catarse.me/mamilos Equipe Mamilos _____ Mamilos é uma produção do B9 A apresentação é de Cris Bartis e Ju Wallauer. Pra ouvir todos episódios, assine nosso feed ou acesse mamilos.b9.com.br Quem coordenou essa produção foi Beatriz Souza. A edição foi de Mariana Leão e as trilhas sonoras, de Angie Lopez. A coordenação digital é feita por Agê Barros. O B9 tem direção executiva de Cris Bartis, Ju Wallauer e Carlos Merigo. O atendimento e negócios é feito por Telma Zennaro.

Mamileiros e mamiletes, O Mamilos esteve na COP 28, pelo segundo ano consecutivo, a convite do Pacto Global da ONU no Brasil e no programa de hoje, o que vocês vão ouvir são as conversas que tivemos com pessoas que estão liderando as transformações necessárias à adaptação à mudança climática no Brasil. Esse programa foi feito pra você que tá ouvindo falar de COP o tempo inteiro, sabe que é importante e tá aí com várias abas abertas sobre o assunto mas não tá dando conta de acompanhar. Nossa missão aqui é, em pouco mais de uma hora, contar pra vocês pra que serve a COP, como o encontro funciona, como o Brasil tem atuando dentro das pautas debatidas e o que ficou estabelecido nesta edição acontecida em Dubai. Dá o play e vem com a gente! _____ SBP Quem nunca passou um tempão tentando matar todos os pernilongos do quarto antes de dormir? E claro que é só apagar a luz e deitar na cama que já vem um zumbido no ouvido pra te mostrar que tinham mais mosquitos escondidos prontinhos pra atrapalhar seu sono. Pra resolver esse problema, SBP lançou um produto novo com uma tecnologia revolucionária. O SBP com Ação Magnética Aerossol caça e mata até 100% dos mosquitos escondidos e difíceis*. Parece magia, mas é verdade: o produto caça e mata 100% dos mosquitos e deixa sua casa e sua família protegidas. Já pensou? Uma ótima solução para acabar com o zumbido na hora do sono. Amar é proteger, e proteger é SBP. Saiba mais em: sbpprotege.com.br (*) 100% de eficácia em testes de laboratório contra mosquitos Aedes aegypti (escondidos) e Culex quinquefasciatus (difíceis). _____ FALE CONOSCO . Email: mamilos@mamilos.me _____ CONTRIBUA COM O MAMILOS Quem apoia o Mamilos ajuda a manter o podcast no ar e ainda participa do nosso grupo especial no Telegram. É só R$9,90 por mês! Quem assina não abre mão. https://www.catarse.me/mamilos _____ Equipe Mamilos Mamilos é uma produção do B9 A apresentação é de Cris Bartis e Ju Wallauer. Pra ouvir todos episódios, assine nosso feed ou acesse mamilos.b9.com.br Quem coordenou essa produção foi Beatriz Souza. A edição foi de Mariana Leão e as trilhas sonoras, de Angie Lopez. A coordenação digital é feita por Agê Barros. O B9 tem direção executiva de Cris Bartis, Ju Wallauer e Carlos Merigo. O atendimento e negócios é feito por Telma Zennaro.

Don't disappoint the Chickadee! Subscribe to the SBP. Citations: https://www.npr.org/2015/09/03/434400838/warning-calls-decoded-squirrels-take-up-bird-alarms-to-foil-the-enemy https://www.nationalgeographic.com/animals/article/nuthatches-chickadees-communication-danger https://www.allaboutbirds.org/news/look-out-the-backyard-bird-alarm-call-network/# https://www.audubon.org/news/a-beginners-guide-common-bird-sounds-and-what-they-mean

Mamileiros e mamiletes, há algumas semanas, fizemos o Mamilos 419 sobre como educar nossos filhos entre o autoritarismo e a permissividade. A conversa foi tão boa, que terminamos o programa com a sensação de que ainda tinha tanto a ser dito que precisávamos de uma parte dois. E pelos comentários que recebemos, vocês também ficaram querendo esticar esse papo! Então, aqui estamos pra segunda parte dessa conversa sobre educação com limites. Naquele primeiro programa, falamos muito sobre o desafio de se equilibrar entre ser autoritário ou permissivo. Neste, queremos focar mais em situações práticas e em como podemos agir da melhor forma diante delas. E como cada faixa etária tem seus desafios particulares, nesse programa vamos focar na fase da pré adolescência. Quais são os limites para dar autonomia sem deixar de proteger? E vamos em boa companhia, sentam na mesa com a gente Ariella Wanner, pedagoga, especializada em neurociência das emoções, e Thais Basile, psicanalista, especialista em psicopedagogia institucional. Esse programa também foi publicado em vídeo no nosso canal do Youtube. Dá o play e vem com a gente! _____ SBP Quem nunca passou um tempão tentando matar todos os pernilongos do quarto antes de dormir? E claro que é só apagar a luz e deitar na cama que já vem um zumbido no ouvido pra te mostrar que tinham mais mosquitos escondidos prontinhos pra atrapalhar seu sono. Pra resolver esse problema, SBP lançou um produto novo com uma tecnologia revolucionária. O SBP com Ação Magnética Aerossol caça e mata até 100% dos mosquitos escondidos e difíceis*. Parece magia, mas é verdade: o produto caça e mata 100% dos mosquitos e deixa sua casa e sua família protegidas. Já pensou? Uma ótima solução para acabar com o zumbido na hora do sono. Amar é proteger, e proteger é SBP. Saiba mais em: sbpprotege.com.br (*) 100% de eficácia em testes de laboratório contra mosquitos Aedes aegypti (escondidos) e Culex quinquefasciatus (difíceis). _____ FALE CONOSCO . Email: mamilos@mamilos.me _____ CONTRIBUA COM O MAMILOS Quem apoia o Mamilos ajuda a manter o podcast no ar e ainda participa do nosso grupo especial no Telegram. É só R$9,90 por mês! Quem assina não abre mão. https://www.catarse.me/mamilos _____ Equipe Mamilos Mamilos é uma produção do B9 A apresentação é de Cris Bartis e Ju Wallauer. Pra ouvir todos episódios, assine nosso feed ou acesse mamilos.b9.com.br Quem coordenou essa produção foi Beatriz Souza. A edição foi de Mariana Leão e as trilhas sonoras, de Angie Lopez. A coordenação digital é feita por Agê Barros. O B9 tem direção executiva de Cris Bartis, Ju Wallauer e Carlos Merigo. O atendimento e negócios é feito por Telma Zennaro.

In episode 194 of America Adapts, we take a deep dive on climate risk and the insurance sector. Earlier in the fall host Doug Parsons attended a two day conference hosted at American University in Washington DC. The conference was organized by Environmental Defense Fund, SBP and American University. The event brought together experts that focus on the role of insurance when it comes to building equity in disaster recovery, reducing future losses, expanding coverage with new innovations, and managing increasing climate-related disasters. You'll hear the need for insurance companies to conduct climate risk analysis and the role of government in addressing these issues. Experts at this conference laid the intellectual groundwork on where the insurance industry will need to go and you'll hear highlights in this episode. This episode was generously sponsored by Environmental Defense Fund. Agenda from the Climate Risk conference available here. Video recordings from the Climate Risk Conference available here. Dr. Carolyn Kousky, Associate Vice President for Economics and Policy at Environmental Defense Fund  Francis Bouchard, Managing Director, Climate, Marsh McLennan  Helen Wiley, Disaster Preparedness Program Director, SBP Janelle Kellerman, Founder The Center for Sea Rise Solutions Rob Moore, Senior Policy Analyst, People & Communities Program, Natural Resources Defense Council  Theodora Makris, Program Manager at Center for NYC Neighborhoods  Kate Stillwell, Founder of Jumpstart Insurance  Doug Heller, Director of Insurance, Consumer Federation of America Topics covered: Managing climate risk Reducing Inequities in Recovery Community Models of Insurance Insurance and Local Government Financial Needs Escalating Climate Risk and Insurance Markets Rethinking public and private strategies for risk transfer Linking flood insurance to buyouts Check out the America Adapts Media Kit here! Subscribe to the America Adapts newsletter here. Donate to America Adapts Listen to America Adapts on your favorite app here! Facebook, Linkedin and Twitter: https://www.facebook.com/americaadapts/ @usaadaptshttps://www.linkedin.com/in/doug-parsons-america-adapts/ https://www.instagram.com/america_adapts/?hl=en Resources and Links in this episode: Inclusive Insurance for Climate-Related Disasters: A Roadmap for the United States SBP's Prepare Program Harnessing Risk Transfer to Support Immediate Post-Disaster Needs of Low- and Moderate-Income Households: A Meso-Insurance Pilot in New York City Improving the Post-Flood Financial Resilience of Lower-Income Households through Insurance Community-Based Catastrophe Insurance Parametric Insurance for Disasters Can Insurance Save us from Climate Disaster? Background on home buyouts: https://www.nrdc.org/bio/anna-weber/going-under-post-flood-buyouts-take-years-complete Jumpstart Insurance California Climate Insurance Working Group Learn your flood risk now: https://www.floodhelpny.org/   Battelle's third annual Innovations in Climate Resilience Conference (ICR24) takes place on April 22-24, 2024, in Washington, DC. This toolkit is meant to help share messaging and information with your audiences.   ICR24 Websitehttps://www.battelle.org/conferences/conference-on-innovations-in-climate-resilience IMPORTANT KEY DATES ·         Abstract Submission Deadline – December 11, 2023 – Submission link Early Bird Registration Opens – November 1, 2023 – Registration link Early Bird Registration Deadline - February 16, 2024 Standard Registration Closes - April 15, 2024 Donate to America Adapts Follow on Apple Podcasts Follow on Android Hey Adapters, I'm excited to announce a new partnership with Atmos. America Adapts has been selected as one of the non-profits that gets direct donations when you start banking with Atmos, the world's most climate-focused bank account. From solar loans, cash-back checking to high yield savings accounts, Atmos is 'banking with a purpose.' When you open a bank account you can increase your monthly savings rate when you regularly support their select list of non profits working for a sustainable future. Yes, there are other options besides America Adapts...like Amazon Watch, 1% for the Planet, Grist, Project Drawdown and many more. Please watch the short video below to get a specific explanation of what Atmos offers. America Adapts gets individual donors because we're a 501(c)3, but Atmos might be a better fit, as you get banking services with your donations.. Doug Parsons and Speaking Opportunities: If you are interested in having Doug speak at corporate and conference events, sharing his unique, expert perspective on adaptation in an entertaining and informative way, more information can be found here! Now on Spotify! List of Previous Guests on America Adapts Follow/listen to podcast on Apple Podcasts. Donate to America Adapts, we are now a tax deductible charitable organization! Federal Reserve Bank of San Francisco Strategies to Address Climate Change Risk in Low- and Moderate-income Communities - Volume 14, Issue 1 https://www.frbsf.org/community-development/publications/community-development-investment-review/2019/october/strategies-to-address-climate-change-low-moderate-income-communities/ Podcasts in the Classroom – Discussion guides now available for the latest episode of America Adapts. These guides can be used by educators at all levels. Check them out here! The 10 Best Sustainability Podcasts for Environmental Business Leadershttps://us.anteagroup.com/news-events/blog/10-best-sustainability-podcasts-environmental-business-leaders The best climate change podcasts on The Climate Advisorhttp://theclimateadvisor.com/the-best-climate-change-podcasts/ 7 podcasts to learn more about climate change and how to fight ithttps://kinder.world/articles/you/7-podcasts-to-learn-more-about-climate-change-and-how-to-fight-it-19813 Directions on how to listen to America Adapts on Amazon Alexa https://youtu.be/949R8CRpUYU America Adapts also has its own app for your listening pleasure!  Just visit the App store on Apple or Google Play on Android and search “America Adapts.” Join the climate change adaptation movement by supporting America Adapts!  Please consider supporting this podcast by donating through America Adapts fiscal sponsor, the Social Good Fund. All donations are now tax deductible! For more information on this podcast, visit the website at http://www.americaadapts.org and don't forget to subscribe to this podcast on Apple Podcasts.   Podcast Music produce by Richard Haitz Productions Write a review on Apple Podcasts ! America Adapts on Facebook!   Join the America Adapts Facebook Community Group. Check us out, we're also on YouTube! Executive Producer Dr. Jesse Keenan Subscribe to America Adapts on Apple Podcasts Doug can be contacted at americaadapts @ g mail . com

The following question refers to Section 4.7 of the 2021 ESC CV Prevention Guidelines. The question is asked by student Dr. Shivani Reddy, answered first by NP Carol Patrick, and then by expert faculty Dr. Eileen Handberg.Dr. Handberg is an Adult Nurse Practitioner, Professor of Medicine, and Director of the Cardiovascular Clinical Trials Program in the Division of Cardiovascular Medicine at the University of Florida. She has served as Chair of the Cardiovascular Team Section and the Board of Trustees with the ACC and is the President Elect for the PCNA.The CardioNerds Decipher The Guidelines Series for the 2021 ESC CV Prevention Guidelines represents a collaboration with the ACC Prevention of CVD Section, the National Lipid Association, and Preventive Cardiovascular Nurses Association.Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values. Question #34 Ms. BW presents after her best friend was diagnosed with hypertension and is interested in measuring her own blood pressure. According to the ESC Guidelines, what BP screening approach is recommended for making a diagnosis of hypertension? ARepeated measurements in one visitBA single measurement in a single visitCRepeated measurements in more than one visit  DReported patient history  Answer #34 Explanation The correct answer is C – Repeated measurements in more than one visit.It is recommended to base the diagnosis of hypertension on repeated office BP measurements on more than one visit except when hypertension is severe (e.g., Grade 3—defined as SBP > 180 and/ or DBP >110mmHg—and especially in high-risk patients) (Class I, LOE C). In addition to recommending repeat measurements across visits, the guidelines provide a number of considerations for appropriately measuring blood pressure, such as taking measurements when seated in a quiet environment for 5 minutes and measuring in both arms at the first visit and using the higher-level value arm for visits thereafter (see Table 14 on page 3283).Additionally, home blood pressure monitoring is recommended as an alternative to repeated office measurements. Blood pressure measurements are taken with a semiautomated, validated cuff for 3 consecutive days – and 6-7 days being preferred – in the morning and at night, averaged over that period. Notably, home blood pressure thresholds for the diagnosis of hypertension are lower than for that of in-office measurements, with a daytime systolic of 135mmHg or diastolic of 85mmHg given as the level at which hypertension is diagnosed, as opposed to 140mmHg and 90mmHg for systolic and diastolic levels, respectively, given for in-office diagnosis.Main TakeawayWith the exception of those with severely elevated blood pressures, the diagnosis of hypertension requires repeated measurements across multiple office visits.Guideline Loc.Sections 4.7.1 and 4.7.2, Table 13 and 14, Figure 14 CardioNerds Decipher the Guidelines - 2021 ESC Prevention SeriesCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor RollCardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron!