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Podcast Journal Club

Podcast Journal Club

By: Giselle Aerni MD and Sonya Del Tredici MD
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Podcast Journal Club is an evidence-based medicine podcast where the residents at Wellspan Health discuss research and medical current events.

 Hygiene & Healthy Living Physical Illness & Disease
Episodes
  • 5. Fluid Resuscitation with Emergency Medicine

    5. Fluid Resuscitation with Emergency Medicine
    22 Nov 2020
    In this episode we discuss two articles about fluid resuscitation. Recorded on 6/25/20.Presenters: Alex Pizarro, MD and Ivana Margi, MD, Wellspan York Hospital Emergency Medicine DepartmentHosts: Giselle Aerni, MD and Sonya Del Tredici, MDProducer: Robert Stuntz, MD Article 1: Balanced Crystalloids versus Saline in Critically Ill Adults. Semler, Et. Al. N Engl J Med 2018 Mar 1;378(9):829-839. The SMART Investigators and the Pragmatic Critical Care Research Group. Notes By Dr. Pizarro.Question: In critically ill patients does the use of balanced crystalloids compared to normal reduce a 30-day composite outcome of death, new renal replacement therapy, and renal dysfunction?Background: Historically normal saline has been the most commonly administered IV fluid; however, its safety has been questioned. Normal saline is a hypertonic, acidotic fluid so far from “normal”.  Balanced crystalloid solutions (such as LR and Plasma-Lyte A) have electrolyte compositions closer to that of plasma which is why they make an excellent alternative! Normal saline causes hyperchloremic metabolic acidosis.  Several studies suggest that normal saline is associated with higher rates of acidosis, acute kidney injury, use of renal replacement therapy, and death.  Evidence that normal saline is associated with:Hemodynamic instability§  Kellum (2004): Septic rats who received normal saline had more profound hemodynamic dysfunction as compared to LR.§  Orbegozo (2016): Sheep who received normal saline had reduced cardiac index, reduced tissue oxygen levels, impaired microcirculatory perfusion, more coagulopathy, earlier development of oliguria, and earlier death.  §  Potura (2015): Retrospective control study on patients undergoing renal transplantation randomized to receive normal saline vs. Elomel Isoton solution (an acetate-buffered balanced crystalloid).  Patients receiving saline required vasopressors more frequently (30% vs 15%; p=0.03)Increased inflammation§  Kellum (2006):  Used hydrochloric acid in septic rats to induce a hyperchloremic acidosis resulting in increased levels of pro-inflammatory cytokines.§  Zhou (2014): In a rat sepsis model, resuscitation with saline produced higher levels of interleukin-6 compared to Plasmalyte.§  Wu (2011): Randomized control trial of patients with pancreatitis comparing LR to normal saline.  Normal saline had higher levels of C-reactive protein one day after the initiation of fluid resuscitation.  Normal saline also seemed to delay resolution of clinical features of systemic inflammation (SIRS criteria).  Based on this study, LR is generally recommended as the fluid of choice for pancreatitis resuscitation by the American College of Gastroenterology guidelines. §  de-Madaria (2018): Replicated Wu (2011) results.  Patients treated with normal saline had a nonsignificant trend towards more SIRS criteria (p=0.06) and increased level of C-reactive protein. Increased risk of acute kidney injury (Theory: hyperchloremia causes renal vasoconstriction which in turn decreases renal cortical blood flow leading to AKI thus increasing the need for renal replacement therapy and risk of death) §  Zhou (2014): In septic rats, saline resuscitation increased the rate of kidney injury compared to Plasmalyte.§  Chawdhury (2012): Patients who received two-liter saline bolus had reduced blood flow to the renal cortex compared to two-liter Plasmalyte. §  Yunos (2012): Before-after study which involved avoiding chloride-rich resuscitative fluids in an ICU.  Following this intervention, the rate of acute kidney injury decreased.  Debunked myths about LR:1. It is cheap – LR is only $0.25 more expensive than normal saline.  2. LR worsens hyperkalemia – Evidence suggests the exact opposite.  In fact, normal saline causes hyperchloremic acidosis which may exacerbate a hyperkalemic state due to shift of H+ intracellularly in exchange for K+.§  Martini (2013): Pig model for hemorrhagic shock found that normal saline is more likely to cause hyperkalemia when compared to LR.§  O’Malley (2005), Khajavi (2008), Modi (2012), and Weinberg (2017): Randomized control trials performed during renal transplant surgery showed that normal saline more frequently causes hyperkalemia when compared to LR or Plasmalyte. Design: Pragmatic, unblinded, cluster-randomized, multiple-crossover trialSetting: Location: Conducted in 5 ICUs at a single US academic center (Vanderbilt in Nashville, TN): Medical (34 beds), Neurologic (22 beds), Cardiac (27 beds), Trauma (31 beds), Surgical (22 beds).Dates: From June 1st 2015 to April 30th 2017Population: Inclusion: All adult patients admitted to the ICUExclusion: Age < 18 yrsSample Size: 15,802 adults Median age: 58-years-oldGender: 57.6% maleNo significant differences in baseline characteristics between groupsHow were they assigned?For every month of the trial, each ICUs was randomized to use saline or balanced crystalloids.  They then ...
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    Less than a minute
  • 4. 5 Notable papers of 2019

    4. 5 Notable papers of 2019
    29 Aug 2020
    Dr. Del Tredici reviews 5 of her favorite papers from 2019. We discuss aortic stenosis, the SGLT2 inhibitors, the safety of PPIs, and whether or not you can treat osteomyelitis with oral antibiotics.Presenter: Sonya Del Tredici, MD Host: Giselle aerni, MDProducer: Robert Stuntz, MDPAPER 1: TAVR and more TAVRTranscatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients MJ Mack, et. al. The PARTNER-3 Investigators. The New England Journal of Medicine, 380 (18): 1695-1705. May 2, 2019.Why is this paper important?More TARVs than SAVRs are performed in the US, but they are traditionally reserved for intermediate and high-risk patients. This trial aimed to evaluate TAVR in low-risk surgical patients with aortic stenosis.What is the clinical question?Population: Patients with severe calcific aortic stenosis and low surgical risk. They excluded patients with low life expectancy, bicuspid aortic valves and disqualifying anatomy. The study included mostly American men, age ~71, 28% with CAD, 30% with DM, 15% with afib.Intervention: Transfemoral TAVR with a balloon-expandable valve, along with ASA+clopidogrel.Comparison: Surgical aortic valve replacement with a bioprosthetic.Outcomes: Patients were followed for 1 year.Primary endpoint: composite of all-cause mortality, stroke, and rehospitalization related to the valve.Secondary endpoints: new-onset afib, length of stay, death (30 d and 1 yr), stroke (30 d and 1 yr), rehospitalization, overall bad outcomes.These outcomes were both clinical and physiological.Is the study valid?I think this was a well-done study, and the conclusions were valid. It was randomized, but non-blinded. They enrolled 1000 patients, which was enough to power the study. The patients were similar at baseline. They had an appropriate intention-to-treat analysis, and pretty complete outcomes data. About 10% of patients in the surgery group withdrew, deciding they didn’t want surgery. The subgroups were pre-specified.Adverse events were reported.Some limitations were that they only collected 1 year of data, and since the patients were relatively young and healthy, they have a lot more than 1 year to go. I would have preferred to see what happened to them over a longer time. It was funded by the manufacturer of the valve, which may have caused some bias as well.What are the results?The results showed that TAVR is safer, has better outcomes at 30 days, and has better outcomes at 1 year. The patients who got a TAVR had shorter length of stay, fewer operative complications, were more likely to be discharged to home. They also had less afib, stroke, major bleeding, rehospitalization, and death. The only thing that was worse for the TAVR group was incidence of new LBBB.How will this study help us in patient care?The patients in this study are similar to my patients. The outcomes were clinically relevant. The benefits were both clinically and statistically significant. And TAVR is both cheaper and easier for patients. Therefore I conclude that this paper establishes TAVR as the treatment of choice for most patients whose anatomy allows it, especially older patients unconcerned about long-term valve durability. From now on surgical risk should no longer determine who should have a TAVR. Instead we can now look at life expectancy, anticoagulation needs, and long-term valve durability.PAPER 2: Doc, I feel fine. Do I have to get my valve replaced?Early Surgery or Conservative Care for Asymptomatic Aortic Stenosis The RECOVERY Trial. D Kang, S Park, S Lee, Et. al. N Eng J Med 382 (2), 111-119, January 9th, 2020Why is this paper important?In asymptomatic patients with aortic stenosis, the ideal time for surgical intervention is not known. Because the surgery is high-risk, previous guidelines recommended only doing valve replacement on symptomatic patients. But asymptomatic patients can die from sudden death, and they can sustain irreversible myocardial damage, causing later morbidity. But now that surgical techniques have improved, perhaps the risk-benefit calculation has changed, and we should be doing valve replacement on patients before they become symptomatic.What is the clinical question?Population: Included: adults with severe AS.The demographics of the participants were Korean adults, enrolled 2010-2015, mean age 64, BMI 24, HTN 40%, high chol 40%, bicuspid aortic valve 60% (which is important because that makes TAVR not an option), degenerative valve 33%.Excluded: symptomatic AS, CHF, other valve problems, and those who were not surgical candidates.Intervention: SAVR (50% mechanical, 50% biological).Comparison: conservative care, but offered surgery if AS became symptomatic. 74% eventually got surgery.Outcomes: primary endpoint: operative mortality (w/in 30 days) or CV death within trial period (4-7 yrs)Secondary endpoint: mortality, stroke, MI, repeat AV surgery, CHF hospitalizationIs the study valid?It is randomized, not blinded, multi-center study. There were 145 ...
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    32 min
  • 3: High Cholesterol with Internal Medicine

    3: High Cholesterol with Internal Medicine
    16 May 2020
    In this episode we discuss two articles about high cholesterol, one dealing with new targets for treatment, and one about the PCSK9 inhibitors.Presenters: Nam Ha, MD and Britney Plotnick, MD, Wellspan York Hospital Internal Medicine Residency ProgramHosts: Giselle Aerni, MD and Sonya Del Tredici, MDProducer: Robert Stuntz, MDArticle 1: A Comparison of Two LDL Cholesterol Targets after Ischemic Stroke. Amarenco, Pierre MD; Kim, Jong MD et al., N Engl J Med 2020; 382:9-19.BackgroundAfter an ischemic stroke of atherosclerotic origin or TIA, guidelines recommend intensive statin therapy to lower serum lipid levels. The SPARCL trial (2006 by the same author) showed a reduction in recurrent stroke with atorvastatin compared to placebo in patients with stroke, and forms the basis for this recommendation. However, a subsequent analysis of the data from that trial showed patients with LDL < 70 had a 28% lower relative risk reduction of stroke than those with LDL < 100 mg/dL. The current guideline recommends a high intensity statin, but does not specify the LDL target. There are limited data on whether a target LDL of 70 is better than a target LDL of 100. Thus, the Treat Stroke to Target trial (TST) was done.What is the clinical question?Population: 3/2010–12/2018, Adults from France and South Korea, ischemic stroke in prior 3 months or TIA within prior 15 days (modified Rankin 0-3), confirmed with imaging. Some patients were on anticoagulation, but the reason was not given.Intervention: Any type and any dose of statin to reach the target of LDL < 70 mg.dL or LDL 90-110 mg/dL. Ezetimibe was also added throughout the follow-up to maintain target. Other interventions also include blood pressure control (target 130/80 in diabetes; less than 140/90 otherwise), hemoglobin A1c%<7, and encouraging smoking cessation.Comparison: Lower target group versus higher target group.Outcomes: Primary endpoints: Nonfatal cerebral infarction or stroke of undetermined origin, nonfatal myocardial infarction, hospitalization for unstable angina followed by urgent coronary revascularization, TIA with urgent carotid revascularization, cardiovascular death (including unexplained sudden death).Secondary endpoints: MI, urgent coronary revascularization after onset of new symptoms, cerebral infarct or urgent revascularization of carotid or cerebral artery after TIA, cerebral infarction with TIA, urgent or elective revascularization of coronary, cerebral, peripheral artery, CVS death, death from any cause, intracranial hemorrhage, newly diagnosed diabetes.Is the trial valid?Randomized? yesBlinded? Blinded adjudicators of events that are components of end pointsGroups similar at baseline? yes, (although a higher percentage of patients in the lower target group were receiving ezetimibe than the higher target one)Follow-up sufficiently long and complete? Maybe. First follow-up was 3 weeks after randomization to adjust medication dose. Follow-up every 6 months after that with measurement of LDL and readjustment of medication as needed. Median follow-up is 5.3 years for French patients vs 2 years for Korean patients (SK patients recruited much later in the trial). Study stopped short due to sponsors lacking funds. Longer follow-up would help see a better picture (e.g. increased incidence of intracranial hemorrhage with LDL target < 70?).Intention to treat analysis? YesWere there enough patients? There were 3760 patients per protocol, but 2873 patients eventually randomized; this may reduce validity of results.Funding bias? Maybe. Study was funded by Pfizer, AstraZeneca, and Merk. Authors received fees.What are the results?Sample size: 2873 patients; 2860 included.Treatment effects: primary endpoint 8.5% in the lower-target (2.27 per 100 person-years) vs 10.9% in the higher-target (2.98 per 100 person-years). Adjusted hazard ratio, 0.78; 95% CI; 0.61-0.98; P=0.04.NNT = 42 for the follow-up intervalAdverse events: Intracranial hemorrhage 18 patients (1.3%) in lower-target vs 13 patients (0.9%) in higher-target. Hazard ratio 1.38, 95% CI, 0.68-2.82. New diabetes in 103 patients (7.2%) in lower-target vs 82 (5.7%) in higher-target. Hazard ratio 1.27; 95% CI, 0.95-1.70.Will the results help me in patient care?Perhaps…in the future. It is good to keep in mind that keeping a lower target LDL is shown here to prevent more cardiovascular events, although the confidence intervals have not been adjusted for multiple comparisons in the trial. Patients, recruited in the FOURIER trial where there was addition of PCSK9 inhibitor for patients with persistent LDL > 70 despite of being on high-dose statin, have LDL level around 30 mg/dL in the intervention group, and these patients have a reduction in major cardiovascular events (including stroke and cardiovascular death).Secondary endpoints such as intracranial hemorrhage could not be statistically analyzed due to hierarchical testing. Perhaps we need more studies to see whether stricter control of LDL can ...
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    18 min
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