NEJM Evidence

Volume 3 Issue 7 of 𝘕𝘌𝘑𝘔 𝘌𝘷𝘪𝘥𝘦𝘯𝘤𝘦 is now available! Here is a preview of the latest content:      𝗢𝗿𝗶𝗴𝗶𝗻𝗮𝗹 𝗔𝗿𝘁𝗶𝗰𝗹𝗲𝘀  Proton-Pump Inhibitors to Prevent Gastrointestinal Bleeding — An Updated Meta-Analysis https://eviden.cc/4aONMBD     Early In-Bed Cycle Ergometry in Mechanically Ventilated Patients https://eviden.cc/4aTe0Tv    Influenza Infection and Acute Myocardial Infarction https://eviden.cc/3RHpRO2    Novel Autologous Dendritic Cell Therapy AVT001 for Type 1 Diabetes https://eviden.cc/4biuOUl    𝗥𝗲𝘃𝗶𝗲𝘄 𝗔𝗿𝘁𝗶𝗰𝗹𝗲  Types of Evidence Needed to Assess the Clinical Value of Diagnostic Imaging https://eviden.cc/3VtuZGk     𝗖𝘂𝗿𝗯𝘀𝗶𝗱𝗲 𝗖𝗼𝗻𝘀𝘂𝗹𝘁  Which Test Should I Order for an Inpatient Evaluation of Cardiac Ischemia? https://eviden.cc/45EeOL7     𝗠𝗼𝗿𝗻𝗶𝗻𝗴 𝗥𝗲𝗽𝗼𝗿𝘁   A 15-Month-Old with Faltering Growth https://eviden.cc/3xutwrp    𝗦𝘁𝗮𝘁𝘀, 𝗦𝗧𝗔𝗧!  How Meta-Analysis Works https://eviden.cc/3KTlsnl    Explore all the latest original research and specialty articles in the July issue: https://eviden.cc/current 

Testing for cardiac ischemia, or for the obstructive coronary artery disease (CAD) that causes cardiac ischemia, is common among hospitalized patients. Many testing options exist. Choosing an appropriate test can be challenging and requires accurate risk stratification. Two major categories of testing are available: stress testing (also known as functional testing) and anatomical testing. Stress testing evaluates specifically for ischemia and can be conducted with or without imaging. Anatomical testing visualizes the obstructive CAD that causes ischemia. An article by Rahul Aggarwal, MD, and Deepak L. Bhatt, MD, MPH, MBA, reviews how to choose an appropriate test for the evaluation of cardiac ischemia in the inpatient setting, using case examples to illustrate the considerations involved.    Read the Curbside Consult article “Which Test Should I Order for an Inpatient Evaluation of Cardiac Ischemia?” by Rahul Aggarwal, MD, and Deepak L. Bhatt, MD, MPH, MBA: https://eviden.cc/45EeOL7    #Cardiology #ClinicalMedicine 

The evidence underlying the use of advanced #DiagnosticImaging is based mainly on diagnostic accuracy studies and not on well-designed trials demonstrating improved patient outcomes. This has led to an expansion of low-value and potentially harmful patient care and raises ethical issues around the widespread implementation of tests with incompletely known benefits and harms. Randomized clinical trials are needed to support the safety and effectiveness of imaging tests and should be required for clearance of most new technologies. Large, diverse cohort studies are needed to quantify disease risk associated with many imaging findings, especially incidental findings, to enable evidence-based management. The responsibility to minimize the use of tests with unknown or low value requires engagement of clinicians, medical societies, and the public.    Read “Types of Evidence Needed to Assess the Clinical Value of Diagnostic Imaging,” the latest review in the Diagnostic Evidence Review series, by Carly Stewart, MHA, Matthew S. Davenport, MD, Diana L. Miglioretti, PhD, and Rebecca Smith-Bindman, MD: https://eviden.cc/3VtuZGk    #MedicalResearch 

Acute respiratory infections can trigger acute myocardial infarction. Annemarijn R. de Boer, MD, PhD, et al. aimed to quantify the association between laboratory-confirmed influenza infection and acute myocardial infarction, particularly in patients with and without known coronary artery disease.      This observational, registry-based, self-controlled case series study evaluated the association between laboratory-confirmed influenza infection and occurrence of acute myocardial infarction. Laboratory records on respiratory virus polymerase chain reaction (PCR) testing from 16 laboratories across the Netherlands were linked to national mortality, hospitalization, medication, and administrative registries. Influenza infection was defined as a positive PCR test result. Acute myocardial infarction was defined as a registered diagnostic code for either acute myocardial infarction hospitalization or death. Using a self-controlled case series method, we then compared the incidence of acute myocardial infarction during the risk period (days 1 to 7 after influenza infection) versus the control period (1 year before and 51 weeks after the risk period).    Continue reading the Original Article “Influenza Infection and Acute Myocardial Infarction” by Annemarijn R. de Boer, MD, PhD, et al.: https://eviden.cc/3RHpRO2     𝗙𝗨𝗥𝗧𝗛𝗘𝗥 𝗥𝗘𝗔𝗗𝗜𝗡𝗚  📄 Editorial by C. Raina MacIntyre, MBBS, FRACP, FAFPHM, PhD, Zubair Akhtar, MPH, and Aye Moa, MPH, PhD: Influenza Vaccine — Low-Hanging Fruit for Prevention of Myocardial Infarction https://eviden.cc/3RE2Jjt  📄 Editorial by Lori E. Dodd, PhD: Influenza and Acute Myocardial Infarction — Causal Link or Spurious Association? https://eviden.cc/3zhs0tl    #Cardiology #MedicalResearch

The original LEAP (Learning Early About Peanut allergy) trial was a randomized controlled trial (RCT) that investigated whether the early introduction of peanut-based foods reduced the development of peanut allergies among high-risk children. The LEAP trial followed children from infancy to 5 years of age.     The LEAP-Trio study, published in NEJM Evidence, builds upon the earlier RCT to explore longer-term outcomes. In the LEAP-Trio study, the authors report on allergy rates in a subset of the original study cohort, now that the children have reached 12 years of age.    In assessing this study statistically, there are three dynamics of importance: the reporting of statistical conclusions, a subtle issue with what “treatment” is being evaluated, and the change in study participants.    Read the editorial "Statistical Considerations When Building upon an Existing Randomized Trial” by Michael Baiocchi, PhD; https://eviden.cc/3UWIzD3    𝗙𝗨𝗥𝗧𝗛𝗘𝗥 𝗥𝗘𝗔𝗗𝗜𝗡𝗚   📄 Original Article by George Du Toit, MB, BCh, Gideon Lack, MB, BCh, et al.: Follow-up to Adolescence after Early Peanut Introduction for Allergy Prevention https://eviden.cc/3V7DWqd  📄 Editorial by Sarita Patil, MD, Stephanie K. Dougan, PhD, and Michael Dougan, MD, PhD: Leaping toward Tolerance https://eviden.cc/3UZFq5L    #Immunology #MedicalResearch 

The clinical phase 1 study of the T regulatory (Treg) cell product CK0801 in nine patients with bone marrow failure syndromes reported by Kadia et al. in NEJM Evidence fits well into the current immunotherapy era. These cells, brought to the forefront by Shimon Sakaguchi two decades ago, constitute a subpopulation of CD4+ T cells characterized by the surface expression of the alpha chain of the interleukin-2 receptor, CD25, the inhibitory molecule CTLA-4, and the intracellular transcription factor FoxP3. They control, under healthy conditions and through several mechanisms, expansion and function of other immune cells, such as effector T cells and natural killer cells. Defective Treg functions lead to autoimmunity but also contribute to other diseases in which the immune system is involved.    In an editorial, Carole Seguin-Devaux, PhD, and Jacques Zimmer, MD, PhD, review the safety and preliminary efficacy results of CK0801. Read the full editorial: https://eviden.cc/4bgUGk8    𝗙𝗨𝗥𝗧𝗛𝗘𝗥 𝗥𝗘𝗔𝗗𝗜𝗡𝗚   Original Article by Tapan Kadia, MD, simrit parmar, MD, MSCI, et al.: Phase 1 Study of CK0801 in Treatment of Bone Marrow Failure Syndromes https://eviden.cc/4bkpyjR    #ClincialTrials #MedicalResearch 

Critical illness requiring invasive mechanical ventilation can precipitate important functional disability, contributing to multidimensional morbidity following admission to an intensive care unit (ICU). Early in-bed cycle ergometry added to usual physiotherapy may mitigate ICU-acquired physical function impairment.    Michelle Kho, PT, PhD, et al. randomly assigned 360 adult ICU patients undergoing invasive mechanical ventilation to receive 30 minutes of early in-bed Cycling + Usual physiotherapy (n=178) or Usual physiotherapy alone (n=182). The primary outcome was the Physical Function ICU Test-scored (PFIT-s) at 3 days after discharge from the ICU (the score ranges from 0 to 10, with higher scores indicating better function).    Read the Original Article “Early In-Bed Cycle Ergometry in Mechanically Ventilated Patients” by Michelle Kho, PT, PhD, et al.: https://eviden.cc/4aTe0Tv 𝗙𝗨𝗥𝗧𝗛𝗘𝗥 𝗥𝗘𝗔𝗗𝗜𝗡𝗚   Editorial by Carol Hodgson, PhD, and Michelle Paton, PhD: Cycling in ICU — Keep Peddling or Push the Brakes? https://eviden.cc/4cdksqb    #CriticalCare #ClinicalTrials 

The LEAP (Learning Early About Peanut allergy) trial established that early introduction of peanuts in high-risk infants prevents the childhood development of peanut allergy for most. LEAP-Trio, a 12-year follow up of the LEAP participants, published in NEJM Evidence, demonstrates long-term protection from peanut allergy. In comparison with the 80% reduction of peanut allergy in LEAP, LEAPTrio found a 75% reduction in the early peanut consumption group compared with the avoidance group, despite ad libitum consumption of peanuts in children who were originally peanut-tolerant. Clinically, LEAP-Trio demonstrates that early introduction of peanuts in high-risk children results in long-lived tolerance. That long-lasting tolerance to peanuts is induced by ingestion during an early developmental window suggests that gastrointestinal exposure is important, though the underlying immunological mechanisms of protection from allergy remain unclear.    Continue reading the editorial “Leaping toward Tolerance” by Sarita Patil, MD, Stephanie K. Dougan, PhD, and Michael Dougan, MD, PhD: https://eviden.cc/3UZFq5L     𝗙𝗨𝗥𝗧𝗛𝗘𝗥 𝗥𝗘𝗔𝗗𝗜𝗡𝗚   📄 Original Article by George Du Toit, MB, BCh, Gideon Lack, MB, BCh, et al.: Follow-up to Adolescence after Early Peanut Introduction for Allergy Prevention https://eviden.cc/3V7DWqd  📄 Editorial by Michael Baiocchi, PhD: Statistical Considerations When Building upon an Existing Randomized Trial https://eviden.cc/3UWIzD3    #Immunology #MedicalResearch 

The goal of this systematic review by Ying Wang, MSc, Deborah Cook, MD, MSc, et al. was to examine the efficacy and safety of proton-pump inhibitors for stress ulcer prophylaxis in critically ill patients.    The authors included randomized trials comparing proton-pump inhibitors versus placebo or no prophylaxis in critically ill adults, performed meta-analyses, and assessed certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations approach. To explore the effect of proton-pump inhibitors on mortality based on disease severity, a subgroup analysis was conducted combining within-trial subgroup data from the two largest trials and assessed credibility using the Instrument for Assessing the Credibility of Effect Modification Analyses.    Read the Original Article “Proton-Pump Inhibitors to Prevent Gastrointestinal Bleeding — An Updated Meta-Analysis” by Ying Wang, MSc, Deborah Cook, MD, MSc, et al.: https://eviden.cc/4aONMBD    𝗙𝗨𝗥𝗧𝗛𝗘𝗥 𝗥𝗘𝗔𝗗𝗜𝗡𝗚  Original Article: Stress Ulcer Prophylaxis during Invasive Mechanical Ventilation (published in NEJM) https://nej.md/3KD01Xp    #CriticalCare #ClinicalTrials 

Since January 2020, there have been over 775 million confirmed cases of Covid-19 and 7 million deaths globally. Vaccinations and increased virologic exposure in the population have attenuated the nature of the clinical illness and reduced the severe outcomes associated with the early pandemic stages. However, there is ongoing global transmission of SARS-CoV-2 and evolution of variant strains, with the potential to cause more serious illness. Only limited antiviral options are available to reduce symptomatic illness and disease progression.    In an editorial, Drs. Amy C. Sherman and Lindsey R. Baden examine a trial of olgotrelvir for outpatient Covid-19 and discuss the potential benefits of the treatment.    Read the full editorial: https://eviden.cc/3UW7FlF    𝗙𝗨𝗥𝗧𝗛𝗘𝗥 𝗥𝗘𝗔𝗗𝗜𝗡𝗚  Original Article by Rongmeng Jiang, MD, Hongzhou Lu, MD, Xiao Xu, MD, et al.: Olgotrelvir as a Single-Agent Treatment of Nonhospitalized Patients with Covid-19  https://eviden.cc/3UVXptz    #ClinicalTrials #MedicalResearch