Peer-reviewed journal featuring in-depth articles to accelerate the transformation of health care delivery. Prepare to become a physician, build your knowledge, lead a health care organization, and advance your career with NEJM Group information and services. The in vitro activity of monoclonal antibodies and antiviral agents was assessed against the sublineages of the SARS-CoV-2 variant of concern omicron (BA.1, BA.1.1, and BA.2). Imai E, Chan JCN, Ito S, et al. ); and University of Hawaii Cancer Center, Honolulu (J.L.B.). The differences between the group with a recurrence score of 10 or lower and the combined randomly assigned groups were significant for age, menopausal status, histologic grade, progesterone receptor status, and surgical procedure (P<0.001 for all comparisons). Because of a rate of nonadherence (12%) that was larger than had originally been projected (5%), the sample size of the group that underwent randomization (i.e., women with a recurrence score of 11 to 25) was increased by 73% (relative to a design with 100% adherence, based on the LachinFoulkes correction),20 which resulted in a target sample size of 6517 eligible patients undergoing randomization. S1 in the Supplementary Appendix). A 5-year rate of invasive diseasefree survival of 90% with chemoendocrine therapy and of 87% or less with endocrine therapy alone, which corresponds to a 32.2% higher risk of an invasive disease recurrence, second primary cancer, or death as a result of not administering chemotherapy (hazard ratio, 1.322), was prespecified as unacceptable.12,14. A booster dose of mRNA-1273 after the initial two-dose vaccination resulted in neutralization titers against the BA.2.75 variant that were similar to those against BA.1 and BA.2 and higher than those against BA.5. Lancet 2012;379:432-444. The spread of the omicron variant produced an increase in Covid-19 in Israel in late 2021, and a second boost of BNT162b2 vaccine was authorized in early January 2022. To account for multiple testing, the weighted BonferroniHolm procedure was used for the primary outcome and the key secondary outcome, followed by a hierarchical testing procedure of additional secondary outcomes, as described previously.16 Because of the formal interim analysis, significance levels for the multiple-testing procedure in the final analysis were adjusted from 1.6667%, 3.3333%, and 5% to 1.5762%, 3.2827%, and 4.9674%, respectively. Panel B shows a sustained decrease of at least 40% in the eGFR from baseline maintained for at least 4 weeks (a component of the primary composite outcome). Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer. The median duration of endocrine therapy was 5.4 years, with similar distributions of durations in the two randomly assigned treatment groups, including approximately 35% rates of adjuvant endocrine therapy extending beyond 5 years (Fig. N Engl J Med 1985;312:665-673. Barriers at multiple levels impede the use of evidence-based medication for opioid use disorder. Further details are provided in the Supplementary Appendix and the trial protocol. Patients who received finerenone had a higher mean serum potassium level than those who received placebo; a maximal difference of 0.23 mmol per liter was observed at month 4, and the difference remained largely stable thereafter (Figure 3B). The standardized definitions for efficacy end points (STEEP) criteria were used for end-point definitions (Section 6B in the Supplementary Appendix).19 The primary end point was invasive diseasefree survival, defined as freedom from invasive disease recurrence, second primary cancer, or death. NEW! Sparano JA, Gray RJ, Makower DF, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. ); National Surgical Adjuvant Breast and Bowel Project Pathology Office (S.P.) Valuable tools for building a rewarding career in health care. Whether removal of these secondary stones improves patient outcomes is unclear. In the as-treated population, some of the differences in baseline characteristics between the treatment groups were significant (Table S3 in Supplementary Appendix). For the purposes of the trial, CKD was defined according to one of two sets of criteria. The trial was performed in accordance with the principles of the Declaration of Helsinki. If you detect resistance to the passage of the swab, back off and try reinserting it at a different angle, closer to the floor of the nasal canal. ); Vanderbilt University, Nashville (I.A.M. Eligible patients were then randomly assigned in a 1:1 ratio to receive oral finerenone or placebo; patients with an eGFR of 25 to less than 60 ml per minute per 1.73 m2 at the screening visit received an initial dose of 10 mg once daily, and those with an eGFR of 60 ml per minute per 1.73 m2 or more at the screening visit received an initial dose of 20 mg once daily. BMC Res Notes 2011;4:122-122. 23. The value of comparative effectiveness research: projected return on investment of the RxPONDER trial (SWOG S1007). Original Article from The New England Journal of Medicine Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients The rate of nonadherence to the assigned treatment was 11.8% overall, including 5.4% among patients who were randomly assigned to receive endocrine therapy alone and 18.4% among those who were randomly assigned to receive chemoendocrine therapy (Table 1). Changing epidemiology of chronic kidney disease as a result of type 2 diabetes mellitus from 1990 to 2017: estimates from Global Burden of Disease 2017. Brentuximab Vedotin with Chemotherapy in Pediatric High-Risk Hodgkins Lymphoma, Early Amino Acids in Extremely Preterm Infants and Neurodisability at 2 Years, Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression, NEJM Catalyst Innovations in Care Delivery. Safety analyses included assessment of adverse events and central laboratory testing; serum potassium and creatinine levels were also measured at local laboratories at all trial visits. These events were classified according to the MedDRA preferred term. Welcome to books on Oxford Academic. Krop I, Ismaila N, Andre F, et al. 1. A data sharing statement provided by the authors is available with the full text of this article at NEJM.org. A complete list of the FIDELIO-DKD investigators is provided in the Supplementary Appendix, available at NEJM.org. N Engl J Med 2010;362:2053-2065. In a 6-month study in children while omicron was dominant, previous SARS-CoV-2 infection and the BNT162b2 vaccine lowered the risks of infection, hospitalization, and death, but protection against omicron declined rapidly. Safety analyses were performed in the safety analysis set (all randomly assigned patients without critical Good Clinical Practice violations who received at least one dose of finerenone or placebo). S5). Abstract Background The initial cases of novel coronavirus (2019-nCoV)infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. Owing to critical Good Clinical Practice violations (including violations that led to the closure of one site and other violations related to patient misconduct), 60 patients were prospectively excluded from all analyses (further details are provided in the Supplementary Appendix), leaving 5674 patients who were included in the statistical analyses. By mid 2022, the vaccine supply will no longer be a limiting factor in efforts to provide more equitable coverage. Bartlett J, Canney P, Campbell A, et al. In a small study involving 54 participants, omicron subvariants BA.2.12.1, BA.4, and BA.5 of SARS-CoV-2 were more likely to escape neutralizing antibodies induced by both vaccination and previous infection than were the prior omicron subvariants BA.1 and BA.2. The incidence was lower among White adults with diabetes than among most other adults with diabetes. Am J Hypertens 2018;31:1165-1174. The primary outcome, assessed in a time-to-event analysis, was a composite of kidney failure, a sustained decrease of at least 40% in the eGFR from baseline over a period of at least 4 weeks, or death from renal causes. After two doses of mRNA vaccine, health care workers had less viral neutralizing-antibody activity against the BA.4/5 and BA.2.12.1 omicron subvariants than against the BA.1 and BA.2 subvariants, but titers increased significantly with a booster dose. Gently insert the swab along the nasal septum, just above the floor of the nasal passage, to the nasopharynx, until resistance is felt (Figure 3). The most effective and engaging way for clinicians to learn, improve their practice, and prepare for board exams. NEW! 18. Distant recurrence was associated with recurrence score as a continuous variable between 11 and 25, but there was no significant interaction between chemotherapy treatment and recurrence score in this range (Figs. Information and tools for librarians about site license offerings. Data from Singapore on BNT162b2 vaccination in children 5 to 11 years of age showed that during a period of omicron-variant predominance, BNT162b2 reduced the risks of SARS-CoV-2 infection and Covid-19related hospitalization. If the recurrence score was 26 or higher, the patient was assigned to receive chemoendocrine therapy. Kwa M, Makris A, Esteva FJ. Carlson RW, Brown E, Burstein HJ, et al. Zelniker TA, Braunwald E. Mechanisms of cardiorenal effects of sodium-glucose cotransporter 2 inhibitors: JACC state-of-the-art review. Sign In or Create Account to save this article, Phase 2 Trial of Baxdrostat for Treatment-Resistant Hypertension, Progression of Atrial Fibrillation after Cryoablation or Drug Therapy, Surgery or Endovascular Therapy for Chronic Limb-Threatening Ischemia, Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease, Duration of Device-Based Fever Prevention after Cardiac Arrest. The serum creatinine level decreased in both recipients. EditorialTime to Stop Using Ineffective Covid-19 Drugs. Ann Intern Med 2009;150:604-612. The map is automatically updated to show current data. Clin Oncol (R Coll Radiol) 2013;25:109-116. Finerenone, a novel selective nonsteroidal mineralocorticoid receptor antagonist protects from rat cardiorenal injury. Breast cancer is the most common cancer in women in the United States and worldwide.1 Hormone-receptorpositive, axillary nodenegative disease accounts for approximately half of all cases of breast cancer in the United States.2 Adjuvant chemotherapy reduces the risk of recurrence,3-5 with effects that are proportionally greater in younger women but that are little affected by nodal status, grade, or the use of adjuvant endocrine therapy.6,7 These findings led a National Institutes of Health consensus panel to recommend adjuvant chemotherapy for most patients,8 a practice that has contributed to declining breast cancer mortality.9 However, the majority of patients may receive chemotherapy unnecessarily. Remove your PPE as shown in the video and described here or in accordance with the standards at your institution. N Engl J Med 2015;372:436-446. Vaccine efficacy during a delta-variant period was 88%. The most trusted, influential source of new medical knowledge and clinical best practices in the world. Brentuximab Vedotin with Chemotherapy in Pediatric High-Risk Hodgkins Lymphoma, Early Amino Acids in Extremely Preterm Infants and Neurodisability at 2 Years, Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression, https://medlineplus.gov/ency/article/003747.htm, https://apps.who.int/iris/bitstream/handle/10665/331329/WHO-COVID-19-laboratory-2020.4-eng.pdf, https://www.cdc.gov/coronavirus/2019-ncov/lab/guidelines-clinical-specimens.html, Prone Positioning of Intubated Patients with an Elevated Body-Mass Index, Use of eFAST in Patients with Injury to the Thorax or Abdomen, Placement of a Double-Lumen Endotracheal Tube, Nasal Cauterization with Silver Nitrate for Recurrent Epistaxis, NEJM Catalyst Innovations in Care Delivery. Bertelsen L, Bernstein L, Olsen JH, et al. Phase 2 Trial of Baxdrostat for Treatment-Resistant Hypertension, Progression of Atrial Fibrillation after Cryoablation or Drug Therapy, Surgery or Endovascular Therapy for Chronic Limb-Threatening Ischemia, Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease, Duration of Device-Based Fever Prevention after Cardiac Arrest. 5. The incidence of the primary composite outcome of kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes was significantly lower in the finerenone group than in the placebo group, occurring in 504 patients (17.8%) and 600 patients (21.1%), respectively (hazard ratio, 0.82; 95% confidence interval [CI], 0.73 to 0.93; P=0.001) (Figure 1A and Figure 2). Pitt B, Kober L, Ponikowski P, et al. 11. The key secondary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. both in Boston. Acute upper gastrointestinal bleeding is a common emergency condition associated with high morbidity and mortality. Concise summaries and expert physician commentary that busy clinicians need to enhance patient care. A digital journal for innovative original research and fresh, bold ideas in clinical trial design and clinical decision-making. NEW! March 2, 2020 (https://apps.who.int/iris/bitstream/handle/10665/331329/WHO-COVID-19-laboratory-2020.4-eng.pdf). Lancet Oncol 2010;11:55-65. Women with a midrange score of 11 to 25 underwent randomization and were assigned to receive either endocrine therapy alone or chemoendocrine therapy. In this double-dummy, randomized, controlled trial, tebipenem pivoxil hydrobromide (an orally bioavailable carbapenem) was noninferior to intravenous ertapenem for the treatment of complicated urinary tract infection. Address reprint requests to Dr. Bakris at the Department of Medicine, University of Chicago, 5841 S. Maryland Ave., MC 1027, Chicago, IL 60637, or at [emailprotected]. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. New research findings are summarized in a short video. 25. Fourth, the mechanisms of action differ between drug classes, including different effects on metabolic, hemodynamic, and diuretic factors and on inflammation and fibrosis.4,13,18,19. Greater protection in the youngest group was noted. ), and Duke University Medical Center, Durham (J.A.O.) Collection of specimens from the surface of the respiratory mucosa with nasopharyngeal swabs is a procedure used for the diagnosis of Covid-19 in adults and children.1-4 The procedure is also commonly used to evaluate patients with suspected respiratory infection caused by other viruses and some bacteria. ), and the Division of Pediatric Oncology, DanaFarber/Boston Childrens Cancer and Blood Disorders Center (K.A.V.)