England Journal Of Medicine Research Articles

Randomized Controlled Trials in ICU in the Four Highest-Impact General Medicine Journals.

To study ICU trials published in the four highest-impact general medicine journals by comparing them with concurrently published non-ICU trials in the same journals. PubMed was searched for randomized controlled trials (RCTs) published between January 2014 and October 2021 in the New England Journal of Medicine , The Lancet , the Journal of the American Medical Association , and the British Medical Journal. Original RCT publications investigating any type of intervention in any patient population. ICU RCTs were defined as RCTs exclusively including patients admitted to the ICU. Year and journal of publication, sample size, study design, funding source, study outcome, type of intervention, Fragility Index (FI), and Fragility Quotient were collected. A total of 2,770 publications were screened. Of 2,431 original RCTs, 132 (5.4%) were ICU RCTs, gradually rising from 4% in 2014 to 7.5% in 2021. ICU RCTs and non-ICU RCTs included a comparable number of patients (634 vs 584, p = 0.528). Notable differences for ICU RCTs were the low occurrence of commercial funding (5% vs 36%, p < 0.001), the low number of RCTs that reached statistical significance (29% vs 65%, p < 0.001), and the low FI when they did reach significance (3 vs 12, p = 0.008). In the last 8 years, RCTs in ICU medicine made up a meaningful, and growing, portion of RCTs published in high-impact general medicine journals. In comparison with concurrently published RCTs in non-ICU disciplines, statistical significance was rare and often hinged on the outcome events of just a few patients. Increased attention should be paid to realistic expectations of treatment effects when designing ICU RCTs to detect differences in treatment effects that are reliable and clinically relevant.

What's hot and why?

What's hot and why?

Visual analysis based on CiteSpace software: a bibliometric study of atrial myxoma.

To use CiteSpace and VOSviewer visual metrology to analyze the research status, frontier hotspots, and trends in research on atrial myxoma. The Web of Science core collection database was used to retrieve relevant literature on atrial myxoma from 2001 to 2022. CiteSpace software was used to analyze keywords with a co-occurrence network, co-polymerization class, and burst terms, and a corresponding visual atlas was drawn for analysis. A total of 893 valid articles were included. The country with the highest number of articles was the United States (n = 186). The organization with the highest number of articles was the Mayo Clinic (n = 15). The author with the highest number of articles was Yuan SM (n = 12). The highest cited author was Reynen K (n = 312). The highest cited journal was Annals of Thoracic Surgery (n = 1,067). The most frequently cited literature was published in the New England Journal of Medicine in 1995, which was cited 233 times. The keywords co-occurrence, copolymerization analysis, and Burst analysis revealed that the main research focuses were surgical methods, case reports, and genetic and molecular level studies on the pathogenesis of myxoma. This bibliometric analysis revealed that the main research topics and hotspots in atrial myxoma included surgical methods, case reports, genetic and molecular studies.

Possibilities of sulodexide use in clinical practice

Introduction. Sulodexide is a polymer, the structure of which includes unbranched polysaccharide chains formed by repeating a particular disaccharide unit. This drug was isolated from the endothelium of the pig, and it appeared on the pharmaceutical market in 1974. Sulodexide contains ≈ 80% heparan sulfate (also known as fast-acting heparin) and 20% dermatan sulfate. This drug is produced from the more sulfated waste heparinoids. During production, heparin is chemically decomposed and transformed into the clinical drug Sulodexide. Aim. To estimate the possibilities and prospects of using the drug Sulodexid in the treatment of various diseases. Materials and methods. During this study, we analyzed relevant sources of domestic and foreign literature on the use of the drug Sulodexid in various pathologies. Sources of information included publications from the Russian scientific electronic library integrated with the Russian Science Citation Index, the Medline database, Scopus, Science Direct, Cyberleninka.ru, and the New England Journal of Medicine. Results and discussion. The pharmacological action of the drug is not limited to anticoagulant action, it also has antiaggregant and angioprotective effects. The drug has found application in various fields of medicine, such as pediatrics, surgery, therapy, endocrinology, neurology and proctology. The possibility of wide application is also promoted by the availability of different forms and methods of administration of this drug: intramuscular, infusion and oral, which allows prescribing the drug both in inpatient and outpatient settings. In contrast to other anticoagulants the drug has the most favorable action, since the risk of bleeding is low. Conclusion. In spite of a sufficiently wide use of the study drug in clinical practice, inclusion in the national clinical guidelines, other effects of the drug require further studies. It is difficult to make a conclusion about the efficacy of the drug in the treatment of some diseases, but with further studies, there is a chance of including it in the therapy of different pathological conditions.

Neoadjuvant Immunotherapy Increases Event-Free Survival in Melanoma

Neoadjuvant Immunotherapy Increases Event-Free Survival in Melanoma

Litifilimab (BIIB059), a promising investigational drug for cutaneous lupus erythematosus

ABSTRACT Introduction There are no U.S. Food and Drug Administration (FDA) approved therapies for cutaneous lupus erythematosus (CLE). Litifilimab is a monoclonal antibody against BDCA2, a plasmacytoid dendritic cell-specific antigen, currently under investigation for systemic lupus erythematosus (SLE) and CLE. The LILAC study, published in the New England Journal of Medicine, is a phase II randomized controlled trial for CLE which demonstrated superiority of Litifilimab over placebo using a skin directed outcome measure. Areas covered This review identifies challenges that have hindered the development of any approved treatments for CLE, recent SLE trials that include skin disease data, and the pharmacological properties of litifilimab. We review the clinical efficacy and safety of litifilimab for both SLE and CLE in the phase I and II clinical trials. This review aims to highlight the need for more CLE-specific clinical trials and examine the potential of litifilimab as the first FDA approved therapy for CLE. (Clinical trial registration: www.clinicaltrials.gov identifier is NCT02847598.) Expert opinion Litifilimab demonstrated efficacy in a randomized phase II clinical trial as a standalone CLE trial using validated skin-specific outcome measures, making it the first successful clinical trial for a CLE targeted therapy. If approved, litifilimab will be a pivotal change in the landscape of CLE management especially for severe and refractory disease.

Treatment‐resistant geriatric depression improves after adding aripiprazole

Older adults with treatment‐resistant depression who received augmentation of their existing antidepressant with aripiprazole experienced significantly greater improvement in psychological well‐being than patients who were switched to bupropion, an open‐label trial has found. Fall rates also were lower in the aripiprazole augmentation group than among patients receiving bupropion augmentation or switching. Results were published online March 3, 2023, in The New England Journal of Medicine.

Trends in women's representation as lead authors in high impact journals of lung cancer.

Women's participation in the clinical oncology practice has increased over the past decade. There is a need to investigate whether women's participation in academia, as reflected by publication activity, increased over the time. This study aimed to investigate trends in female authorship in top journals of lung cancer in the past ten years. In this cross-sectional study of all original research and review articles published in lung cancer journals including New England Journal of Medicine, Lancet journals, JAMA journals, Journal of Clinical Oncology, Annals of Oncology, Cancer Discovery, Journal of Thoracic Oncology, and Translational Lung Cancer Research (TLCR) between 2012 and 2021, the sex composition of lead authors were analyzed. The sex of the author was confirmed by internet searching for photographs, biographies, and gender-specific pronouns from journal or personal websites. The time-trend of female authorship was determined using Join-Point Regression (JPR) analysis. A total of 3,625 first authors and 3,612 corresponding authors were identified in the journals during the years studied. The sex of the author was revealed for 98.5%. Among 3,625 first authors with the sex being revealed, 1,224 (33.7%) were women. The proportion of female first authors increased remarkably from 29.4% in 2012 to 39.8% in 2021. The annual percentage change (APC) in female first authorship took place in 2019 [APC for 2019-2021, 37.03, 95% confidence interval (CI): 18.0-59.1, P=0.003]. The proportion of first authors in TLCR increased from 25.9% in 2012 to 42.8% in 2021 and showed the greatest rise in female first authorship. There were significant discrepancies in the female first authorship across the journals and regions. Among the 3,612 corresponding authors whose sex were determined, 884 (24.5%) were female. There is no significant increasing trend in female corresponding authorship. The sex gap in the first authorship of lung cancer research articles has improved markedly in the recent years, however, sex imparities persist especially in corresponding authorship. There is an urgent need to proactively support and promote women in taking the leadership roles, thereby increasing their contributions to and influence on the development or advancement for future healthcare policies and practices.

A Bibliometric Analysis of the Most Cited Journal Articles in Kidney Transplantation.

Citation analysis uses the number of times an author, article, or publication has been cited to determine its relative importance or effect. To provide an overview and identify the articles that have gotten the most attention in the field of kidney transplantation, this bibliometric analysis was conducted to analyze the top 100 most cited articles in the Scopus database. The search terms "kidney" and "renal"and transplant-related words such as "transplant," "donor," "recipient," and "procurement" were used to search the Scopus database. Articles up to the query date of December 21, 2022, were included, and all document types including articles, reviews, conference papers, editorials, book chapters, and meeting abstracts were analyzed. The analysis focused on authors, annual trends, journals, and countries. A total of 68,271 articles related to kidney transplantation were published in the Scopus database up to the search date of December 21, 2022. The top 100 cited papers had a total of 76,029 citations, with a mean citation count of 760.3 ± 284.6. The most cited article was a clinical practice guideline paper published by the Kidney Disease: Improving Global Outcomes (KDIGO) Work Group. The top cited journals were the New England Journal of Medicine, Transplantation, and the American Journal of Transplantation. The most productive authors were primarily based in the United States, with the most frequently cited first author being Kasiske B.L. The greatest number of articles and citations were published between 2000 and 2005. This bibliometric analysis provides a comprehensive overview of the top cited articles in the field of kidney transplantation. The results highlight the most influential and impactful research, as well as the most productive authors, journals, and countries. These findings can be used to guide future research and support decision-making in funding and policy.

Statistical analyses of ordinal outcomes in randomised controlled trials: protocol for a scoping review

IntroductionRandomised controlled trials (RCTs) aim to assess the effect of one (or more) unproven health interventions relative to other reference interventions. RCTs sometimes use an ordinal outcome, which is an endpoint that comprises of multiple, monotonically ordered categories that are not necessarily separated by a quantifiable distance. Ordinal outcomes are appealing in clinical settings as specific disease states can represent meaningful categories that may be of clinical importance to researchers. Ordinal outcomes can also retain information and increase statistical power compared to dichotomised outcomes and can allow multiple clinical outcomes to be comprised in a single endpoint. Target parameters for ordinal outcomes in RCTs may vary depending on the nature of the research question, the modelling assumptions and the expertise of the data analyst.The aim of this scoping review is to systematically describe the use of ordinal outcomes in contemporary RCTs. Specifically, we aim to: bullet Identify which target parameters are of interest in trials that use an ordinal outcome, and whether these parameters are explicitly defined. bullet Describe how ordinal outcomes are analysed in RCTs to estimate a treatment effect. bullet Describe whether RCTs that use an ordinal outcome adequately report key methodological aspects specific to the analysis of the ordinal outcome. Results from this review will outline the current state of practice of the use of ordinal outcomes in RCTs. Ways to improve the analysis and reporting of ordinal outcomes in RCTs will be discussed.Methods and analysisWe will review RCTs that are published in the top four medical journals (British Medical Journal, New England Journal of Medicine, The Lancet and the Journal of the American Medical Association) between 1 January 2012 and 31 July 2022 that use an ordinal outcome as either a primary or a secondary outcome. The review will identify articles through a PubMed-specific search strategy. Our review will adhere to guidelines for scoping reviews as described in the PRISMA-ScR checklist. The study characteristics and details of the study design and analysis, including the target parameter(s) and statistical methods used to analyse the ordinal outcome, will be extracted from eligible studies. The screening, review and data extraction will be conducted using Covidence, a web-based tool for managing systematic reviews. The data will be summarised using descriptive statistics.

Is financial toxicity captured in quality of life assessments in oncology randomized clinical trials?

BackgroundFinancial difficulties in relation with diagnosis and treatment of patients with cancer affects their quality-of-life (QoL). We aim to characterize how financial toxicity was captured in oncology randomized clinical trials (RCTs), and to estimate how often the study-drug or other expenses were covered by sponsors. MethodsThis was a cross-sectional analysis of articles published in six high impact journals (The New England Journal of Medicine, The Lancet, JAMA, The Lancet Oncology, Journal of Clinical Oncology, and JAMA Oncology). Selected articles needed to report on a RCT published between January 2018 and December 2019, study an anti-cancer drug, and have reported QoL results. We abstracted the QoL questionnaires used; whether the survey was directly assessing financial difficulties; whether a difference in financial toxicity was reported between arms; and whether the sponsor supplied the study-drug or covered other expenses. ResultsFor all 73 studies that met inclusion criteria, 34 studies (47%) utilized QoL questionnaires without direct assessment of financial difficulties. The study drug was provided by the sponsor in at least 51 trials (70%), provided according to local rules in 3 trials (4%), and undetermined in the remaining 19 trials (26%). We found 2 trials (3%) with payments or compensation to enrolled patients. ConclusionThis cross-sectional study found 47% of articles reporting on QoL in oncology RCTs did not use QoL questionnaires directly assessing financial toxicity. Additionnaly, the study drug was supplied by the sponsor in most trials. Financial toxicity occurs in real-life settings when patients have to pay for the drugs and other medical expenses. QoL assessments from oncology RCTs lack generalizability to real-world settings, due to limited querying of financial toxicity. Policy summaryReal-world evidence could be demanded by regulators as post-requirement studies to ensure QoL results observed in trials will replicate in patients treated outside investigational trials.

Definition and rationale for placebo composition: Cross-sectional analysis of randomized trials and protocols published in high-impact medical journals.

Inadequate description of trial interventions in publications has been repeatedly reported, a problem that extends to the description of placebo controls. Without describing placebo contents, it cannot be assumed that a placebo is inert. Pharmacologically active placebos complicate accurate estimation and interpretation of efficacy and safety data. In this study, we sought to assess whether placebo contents are described in study protocols and publications of trials published in high-impact medical journals. We identified all placebo-controlled randomized clinical trials (RCTs) published in 2016 in Annals of Internal Medicine, The BMJ, the Journal of the American Medical Association (JAMA), The Lancet, and the New England Journal of Medicine (NEJM). We included all trials with publicly available study protocols. From journal publications and associated study protocols, we searched and recorded: description of placebo contents; the amount of each placebo ingredient; and investigators' stated rationale for selection of placebo ingredients. We included 113 placebo-controlled RCTs. Of the 113 trials, placebo content was described in 22 (19.5%) journal publications and 51 (45.1%) study protocols. The amount of each placebo ingredient was described in 15 (13.3%) journal publications and 47 (41.6%) study protocols. None of the journal publications explained the rationale for the choice of placebo ingredients, whereas a rationale was provided in 4 (3.5%) study protocols. The stated rationales were to ensure the placebo was visually indistinguishable from the experimental intervention (N = 3) and ensure comparability with a previous study (N = 1). There is no accessible record of the composition of placebos for approximately half of high-impact RCTs, even with access to study protocols. This impedes reproducibility and raises unanswerable questions about what effects-beneficial or harmful-the placebo may have had on trial participants, potentially confounding an accurate assessment of the experimental intervention's safety and efficacy. Considering that study protocols are unabridged, detailed documents describing the trial design and methodology, the fact that less than half of the study protocols described the placebo contents raises concerns about clinical trial transparency. To improve the reproducibility and potential of placebo-controlled RCTs to provide reliable evidence on the efficacy and safety profile of drugs and other experimental interventions, more detail regarding placebo contents must be included in trial documents.

Prolific non-research authors in high impact scientific journals: meta-research study.

Journalistic papers published in high impact scientificjournals can be very influential, especially in hot fields. This meta-research analysis aimed to evaluate the publication profiles, impact, and disclosures of conflicts of interest of non-research authors who had published > 200 Scopus-indexed papers in Nature, Science, PNAS, Cell, BMJ, Lancet, JAMA or New England Journal of Medicine. 154 prolific authors were identified, 148 of whom had published 67,825 papers in their main affiliated journal in a non-researcher capacity. Nature, Science, and BMJ have the lion's share of such authors. Scopus characterized 35% of the journalistic publications as full articles and another 11% as short surveys. 264 papers had received more than 100 citations. 40/41 most-cited papers in 2020-2022 were on hot COVID-19 topics. Of 25 massively prolific authors with > 700 publications in one of these journals, many were highly-cited (median citations 2273), almost all had published little or nothing in the Scopus-indexed literature other than in their main affiliated journal, and their influential writing covered diverse hot topics over the years. Of the 25, only 3 had a PhD degree in any subject matter, and 7 had a Master's degree in journalism. Only the BMJ offered conflicts of interest disclosures for prolific science writers in its website, but even then only 2 of the 25 massively prolific authors disclosed potential conflicts with some specificity. The practice of assigning so much power to non-researchers in shaping scientific discourse should be further debated and disclosures of potential conflicts of interest should be emphasized.

Gender Bias in Clinical Trial Enrollment: Female Authorship Matters

Despite initiatives to promote equal enrollment of human subjects in clinical trials, females continue to be underrepresented. The goal of this work is to determine if female enrollment in human clinical trials published in 3 high-impact journals from 2015 to 2019 is correlated with gender of first and/or senior authors. Clinical trials published in the Journal of the American Medical Association (JAMA), The Lancet, and the New England Journal of Medicine (NEJM) from January 1, 2015, to December 31, 2019, were reviewed. Trials were excluded for ongoing enrollment, sex-specific disease research, or author name without gender assignment. One-sample χ2 pairwise comparisons and two-tailed proportion tests on the proportion of females between gender author pairings were done overall and for each subset analysis. In total, 1,427 articles enrolled a total of 2,104,509 females and 2,616,981 males (44.6% vs. 55.4%, P≤0.0001) in clinical trials. Overall, more females were enrolled if both first and senior authors were female (51.7% vs. 48.3%, P≤0.0001). Proportion of females enrolled decreased with the following first and senior author pairings: female-male (48.9%), male-female (48.6%), and male-male (40.5%, P≤0.0001 compared to female-female authorship). Greater female enrollment in clinical trials with female-female compared to male-male authorship persisted in subset analyses by funding source, phase, randomization for study participants, drug and/or device trial, and geographic location. Female enrollment was higher in 3 surgical specialties: neurosurgery (all authors: 52%, P≤0.01), ophthalmology (all authors: 53.6%, P≤0.0001), and surgery (all authors: 54.4%, P≤0.0001). The majority of surgical specialties did not publish trials with female-female authorship but when stratifying by author gender pairing, surgical oncology had the highest female enrollment with female-female authorship (98.4%, P≤0.0001). Female authorship of clinical trial publications, specifically having both first and senior authors as female, was correlated with higher female enrollment in clinical trials when compared to male authorship and endured with multiple subset analyses.

Biology and Belonging.

Biology and Belonging.

Plain language summary of the INCREASE study: inhaled treprostinil (Tyvaso) for the treatment of pulmonary hypertension due to interstitial lung disease.

Here, we summarize the results from the INCREASE study, originally published in the New England Journal of Medicine. The INCREASE study looked at how well a medication called inhaled treprostinil works and how safe it is, compared to placebo (a fake medication), in adults who have pulmonary hypertension associated with interstitial lung disease or PH-ILD. A total of 326 participants took part in the study. Half the participants took inhaled treprostinil and the other half took placebo. After 16weeks, the INCREASE study showed that participants with PH-ILD who took inhaled treprostinil could walk around 31meters (102feet) further than the participants who took placebo. Participants taking inhaled treprostinil also had a decrease in NT-proBNP, which is a protein found in the blood. Lower NT-proBNP levels suggest that the heart is functioning better compared with higher levels. Participants taking inhaled treprostinil showed a decrease of NT-proBNP of 15% compared to a 46% increase in participants taking placebo. More participants taking placebo had worsening of their PH-ILD (33%) compared to participants taking inhaled treprostinil (∼23%). The most common side effects reported in the study were cough, headache, and shortness of breath. In the INCREASE study, on average, people with PH-ILD taking inhaled treprostinil, were able to be more active and had less chance of their PH-ILD getting worse, compared to placebo. Based on inhaled treprostinil showing positive results in most people with PH-ILD in this study, the drug has been approved in the USA for the treatment of PH-ILD. Clinical Trial Registration: NCT02630316 (ClinicalTrials.gov).

The 100 most cited papers in nasopharyngeal carcinoma between 2000 and 2019: a bibliometric study.

To identify the 100 most-cited papers that have contributed to the understanding and treatment of nasopharyngeal carcinoma (NPC). We searched the NPC-related papers between 2000 and 2019 using the Web of Science database on October 12, 2022. Papers were identified in descending order according to the number of citations. The top 100 papers were analyzed. These 100 most cited papers on NPC have been cited for a total of 35,273 times, with a median number of citations of 281 times. There were 84 research papers and 16 review papers. The Journal of Clinical Oncology (n=17), International Journal of Radiation Oncology Biology Physics (n=13), and Cancer Research (n=9) published the most papers. Cancer Epidemiology Biomarkers & Prevention, Lancet, Cancer Cell, Molecular Cancer, and the New England Journal of Medicine had the largest average citations per paper. China contributed the most papers (n=71), followed by USA (n=13), Singapore (n=4) and, France (n=4). There were 55 clinical research papers and 29 laboratory research papers. Intensity-modulated radiation therapy technology (n=13), concurrent chemoradiotherapy (n=9), and neoadjuvant chemoradiotherapy (n=5) were the top three research topics. Epstein-Barr virus-related genes (n=9) and noncoding RNA (n=8) were the research domains in laboratory research papers. The top three contributors were Jun Ma (n=9), Anthony T C Chan (n=8), and Anne Wing-Mui Lee (n=6). This study provides an overview of the major areas of interest in the field of NPC with bibliometric analyses. This analysis recognizes some important contributions in the field of NPC and stimulates future investigations in the scientific community.

Investigating Empirical evidence on the Epidemiology, Diagnosis and Bibliometric analysis of the 100 topmost cited publications on Tuberculosis Disease

Tuberculosis (TB) disease remains a growing threat in public health globally. This study explored the epidemiology, diagnosis, management, and bibliometric analysis of the top 100 most cited articles on TB. The study adopted a narrative review and bibliometric analysis to explore publications on TB disease. Publications in the Web of Science were retrieved to provide extensive selection process. The present study of top 100 articles which are mostly cited are reported between 1969 to 2018. Reported documents were published in 37 journals, and a total of 1058 authors contributed with 10.5 authors per document, and 12 countries contributed, with most of TB research originating from the US (N=51) articles. We found 1058 occasional authors, and of these, 971 authors (0.003%) presented only three articles, followed by 11 authors (0.010%) and 18 authors (0.017%), respectively. About (n=34) research was published in General &amp; Internal Medicine and Science &amp; Technology. New England Journal of Medicine with 14 was top journal. The lead research institution was the University of Cape Town. The significant correlations were found between the number of citations and documents per year (r=0.9579, p&lt;0.0001), countries (r=0.9570, p&lt;0.0001), article per journal (r=0.8721, p&lt;0.0001), and authors (r=0.4601, p&lt;0.0001), and documents per Institution (r=0.6159, p&lt;0.0001). A new insight into TB scientific production was through social network. The evidence from this study provides a template for understanding the epidemiology of TB and the trends in research. It also exposes the hotspot of research along with research gaps for future studies.

Spotlight in Plastic Surgery: April 2023.

Spotlight in Plastic Surgery: April 2023.

Metrology and visualization analysis of literatures related to tumor immunotherapy based on CiteSpace

AbstractTo explore the development of global tumor immunotherapy in the past 20 years, and analyze the research status, hotspots and trends to provide theoretical support for subsequent research. CiteSpace 5.6.R2 software were used to analyze 290 articles related to tumor immunotherapy research from the Web of Science core data set from 2000 to 2019. CiteSpace was used to draw related visual maps and tables of coauthors, cooperating countries, cooperating institutions, literature and journal co‐citation, keyword co‐occurrence, and cluster analysis. The total amount of papers published in the field of tumor immunotherapy research has gradually increased. After receiving the Nobel Prize in Physiology or Medicine in 2018, the number of papers published in the field of research in tumor research reached 20. We found that the United States has the largest number of papers in all countries and China ranks 6. “Proceedings of the National Academy of Sciences of the United States of America,” “Journal of Immunology,” “Cancer Research,” “New England Journal of Medicine,” “Blood” is the top five core academic journals in this field. Cancer, disease, and tumor necrosis factor are the three keywords with the highest highlighting intensity. Comprehensive analysis shows that the coauthors, co‐institutions, and co‐cited journals of the literature are mostly concentrated in the United States. The rise of immunotherapy provides a new direction for tumor treatment. From 2018 to 2019, the number of literatures on tumor immunotherapy worldwide increased sharply. Immunotherapy combined with specific diseases is the current research frontier and hotspot.