Journal Of Medicine Research Articles

Mastering the Sequential Organ Failure Assessment Score: Critical Choices of Score Statistic, Timing, Imputations, and Competing Risk Handling in Major Trials-A Systematic Review.

The Sequential Organ Failure Assessment (SOFA) score originated as a tool for assessing organ dysfunction in critical illness but has expanded to become an outcome measure in clinical trials. We aimed to assess how the SOFA score was used as the primary or secondary endpoint of major randomized controlled trials (RCTs). Independent reviewers searched MEDLINE/PubMed, Scopus, and Embase databases. Articles were selected when they fulfilled: 1) RCT; 2) SOFA score was primary or secondary endpoint; and 3) published in the Lancet, New England Journal of Medicine, or Journal of the American Medical Association. Data collection included study details, outcomes, statistical differences in SOFA score, choice of score statistics, timepoints of SOFA reporting, and how missing data and competing risks analysis were managed. Twenty-three RCTs had SOFA score as outcome measure, eight used it as primary endpoint. Daily maximum SOFA was the key statistic in 11 RCTs, delta SOFA was used in eight, and mean SOFA in four. Mean SOFA was most frequently chosen as primary endpoint (4/8, 50%). There were 18 different outcome assessment timepoints, ranging from 1 to 28 days. Three RCTs reported statistically significant difference in SOFA between groups. Handling of missing SOFA scores was not described in ten of 23 RCTs. When described, it varied from study to study with variable imputation methods and variable accounting for the competing risk of mortality and ICU discharge. There is major variability in the choice of summary statistic for SOFA score analysis and assessment timepoints, when using it as outcome measure in RCTs. There was either no information or great variability in the handling of missing values, use of imputation, and accounting for competing risk. The current use of SOFA scores in RCTs lacks sufficient reproducibility and statistical and methodological robustness.

Publication Pressure in Nuclear Medicine.

The aims of this study were to determine the publication pressure perceived by nuclear medicine scientists and to identify associated determinants. Corresponding authors who published in Clinical Nuclear Medicine, Journal of Nuclear Medicine, or European Journal of Nuclear Medicine and Molecular Imaging between 2021 and 2023 were invited to participate in this survey study. Publication pressure was assessed using the revised Publication Pressure Questionnaire in the domains of "publication stress" (stress due to perceived pressure to publish), "publication attitude" (attitude regarding current publication culture), and "publication resources" (resources when working on publications or experiencing stress when working on publishing), with 5-point Likert scales. A total of 181 individuals participated. Median Publication Pressure Questionnaire scores in the domains "publication stress," "publication attitude," and "publication resources" were 3.33, 3.33, and 2.17, respectively. None of the researchers' characteristics were significantly associated with publication stress. Age >65 years was significantly associated with a more positive view on the publication climate (β coefficient of -0.552, P = 0.007). Several variables were significantly associated with a perception of fewer factors available to alleviate publication pressure: age 45-54 years (β coefficient of 0.249, P = 0.030), age 55-64 years (β coefficient of 0.421, P = 0.002), associate professor position (β coefficient of 0.398, P < 0.001), fellow/resident position (β coefficient of 0.355, P = 0.007), <5 years of research experience (β coefficient of 0.410, P = 0.026), and 5-10 years of research experience (β coefficient of 0.361, P = 0.003). Publication pressure among nuclear medicine scientists is appreciable. Several researcher characteristics appear to be associated with vulnerability to publication pressure.

RETRACTION: Effects of Strength and Endurance Training on Antioxidant Enzyme Gene Expression and Activity in Middle-Aged Men.

D. García-López, K. Häkkinen, M. J. Cuevas, E. Lima, A. Kauhanen, M. Mattila, E. Sillanpää, J. P. Ahtiainen, L. Karavirta, M. Almar, and J. González-Gallego, "Effects of Strength and Endurance Training on Antioxidant Enzyme Gene Expression and Activity in Middle-Aged Men," Scandinavian Journal of Medicine and Science in Sports 17, no. 5 (2007): 595-604, https://doi.org/10.1111/j.1600-0838.2006.00620.x. The above article, published online on 20 February 2007 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, José A. Calbet, and John Wiley & Sons Ltd. Following publication, concerns were raised by a third party that portions of Figure1 were duplicated. Internal investigation confirmed the duplications in this figure, as well as in Figure2, and splicing in Figure2. The authors provided original data, but these were not sufficient to resolve the concerns, and the authors were unable to provide a satisfactory explanation to address the concerns. The retraction has been agreed because of concerns that the images were manipulated, affecting the interpretation of the data and results presented. The authors disagree with this decision.

The fate of manuscripts rejected by the Turkish Journal of Physical Medicine and Rehabilitation

Objectives: The aim of this study was to evaluate the fate of the articles after they were rejected from the Turkish Journal of Physical Medicine and Rehabilitation (Turk J Phys Med Rehab). Materials and methods: Between January 2016 and December 2021, rejected manuscripts by the Turk J Phys Med Rehab were retrospectively analyzed and whether these rejected articles were published in another journal was identified. For the manuscripts published elsewhere, article type, change in the article name, and the number and order of authors were noted. The index of the new journal, the impact factor for SCI-E journals and journal quartile were recorded. Whether the journal was a national journal/international journal, a specialty or non-specialty journal, and whether the impact factors were higher, lower, or the same as Turk J Phys Med Rehab were evaluated. Results: Totally, 76% of 1,051 rejected articles were accepted for publication in another journal, after an average of 13.73 months. The name of the article, the order of the authors, and the number of the authors remained unchanged in 71.4%, 79.3%, and 80.8% of the articles, respectively. A total of 69.9% of the journals were non-specialty journals and 61.8% were general international medical journals. In addition, 32.6% of the journals were included in the SCI-E, and 70.9% of the articles in SCI-E were included in the Q4 and Q3 scope. The impact factor with 51.9% were lower or the same with the Turk J Phys Med Rehab. Conclusion: Our study results showed that a high percentage of the articles rejected by the Turk J Phys Med Rehab found a place in another journal later, and that non-specialty journals that accept general articles were more prominent in the selection of journal. The fact that an article rejected from a journal can be corrected and amended in accordance with valuable reviewer comments by improving its academic quality and seeking success in other journals may be promising for researchers who submit their articles to journals.

Heart Failure and All-Cause Hospitalizations in Patients With Heart Failure

Heart failure (HF) hospitalization is a common end point in HF trials; however, how HF hospitalization is associated with all-cause hospitalization in terms of proportionality, correlation of treatment effects, and concomitant reporting has not been studied. To determine the ratio of HF to all-cause hospitalizations, whether reported treatment effects on HF hospitalization are associated with treatment effects on all-cause hospitalization, and how often all-cause hospitalization is reported alongside HF hospitalization. PubMed was searched from inception to September 2, 2024, for randomized clinical trials (RCTs) of HF treatments using MeSH (medical subject heading) terms and keywords associated with heart failure, ventricular failure, ventricular dysfunction, and cardiac failure, as well as the names of specific journals. RCTs of HF treatments and reporting on HF hospitalization published in 1 of 3 leading medical journals (New England Journal of Medicine, The Lancet, or JAMA). The PRISMA guidelines were followed. Data extraction was performed by 2 reviewers, and disagreements were resolved by consensus. Trial baseline characteristics and outcome data on HF and all-cause hospitalizations were extracted. The ratio of HF to all-cause hospitalizations was calculated. The association of HF hospitalization effects with all-cause hospitalization effects was evaluated using hierarchical bayesian models with weak priors. The posterior distribution was used to calculate the HF hospitalization treatment effects that would need to be observed before a high probability (97.5%) of a reduction in all-cause hospitalization could be achieved. The proportion of trials reporting all-cause hospitalization was calculated. HF and all-cause hospitalizations. Of 113 trials enrolling 261 068 patients (median proportion of female participants, 25.4% [IQR, 21.3%-34.2%]; median age, 66.2 [IQR, 62.8-70.0] years), 60 (53.1%) reported on all-cause hospitalization. The weighted median ratio of HF to all-cause hospitalizations was 45.9% (IQR, 30.7%-51.7%). This ratio was higher in trials with greater proportions of New York Heart Association class III or IV HF, with lower left ventricular ejection fractions, investigating nonpharmaceutical interventions, and that restricted recruitment to patients with HF and reduced ejection fraction. Reported effects on HF and all-cause hospitalizations were well-correlated (R2 = 90.1%; 95% credible interval, 62.3%-99.8%). In a large trial, the intervention would have to decrease the odds of HF hospitalization by 16% to ensure any reduction, 36% to ensure a 10% reduction, and 56% to ensure a 20% reduction in the odds of all-cause hospitalization with 97.5% probability. In this meta-analysis of HF trials, all-cause hospitalization was underreported despite a large burden of non-HF hospitalizations. Large reductions in HF hospitalization must be observed before clinically relevant reductions in all-cause hospitalization can be inferred.

Assessment of the piriformis muscle and piriformis syndrome via Web of Science database: A bibliometric analysis

Background: Piriformis syndrome, which is seen as the cause of 0.3% to 6% of low back pain, is a painful condition that occurs as a result of compression of the piriformis muscle on the sciatic nerve. Although there are many studies in the literature about piriformis syndrome, no bibliometric analysis has been found. This study aims to evaluate piriformis syndrome and conduct a bibliometric analysis of studies related to piriformis muscle and syndrome. Methods: This study was conducted on March 27, 2024, using data recorded in the Web of Science Core Collection Database. The search was made as “Topic = Piriformis OR Piriformis Syndrome.” Accordingly, 1345 results were found, and as a result of the necessary inclusion and exclusion criteria, 961 documents remained. The data was transferred to the VOSviewer software for further analysis. Results: 961 documents based on piriformis muscle or piriformis syndrome were obtained. The country with the most publications was reported to be the USA with 31.42%. Other countries are ranked at around 5% or less. While 9 of the top 10 most cited institutions are based in the USA, clinics that make significant research contributions also attract attention among these institutions. Journals that publish articles containing piriformis syndrome are prominently surgery, physical therapy, anatomy, and general medicine journals. The most repeated keywords were reported as piriformis syndrome, diagnosis, pain, muscle, sciatic nerve, and hip. In contrast, the most repeated clinical terms were reported as approach, surgery, piriformis muscle, injection, sciatica, and compression. Conclusion: The findings obtained in this study are thought to be important for understanding to providing literature with new perspectives on this subject. They will also focus on the missing parts of the subject from this perspective. Also, this study would provide a novel perspective to the studies about piriformis syndrome and contribute to the researchers about the limits of the topic, and being aware of the active journals that publish papers on this issue would facilitate the work of the researchers.

Abstracts from international emergency medicine journals

Editor’s note: EMJ has partnered with the journals of multiple international emergency medicine societies to share from each a highlighted research study, as selected by their editors. This edition will...

Added Value of Medical Subject Headings Terms in Search Strategies of Systematic Reviews: Comparative Study.

The massive increase in the number of published scientific articles enhances knowledge but makes it more complicated to summarize results. The Medical Subject Headings (MeSH) thesaurus was created in the mid-20th century with the aim of systematizing article indexing and facilitating their retrieval. Despite the advent of search engines, few studies have questioned the relevance of the MeSH thesaurus, and none have done so systematically. The objective of this study was to estimate the added value of using MeSH terms in PubMed queries for systematic reviews (SRs). SRs published in 4 high-impact medical journals in general medicine over the past 10 years were selected. Only SRs for which a PubMed query was provided were included. Each query was transformed to obtain 3 versions: the original query (V1), the query with free-text terms only (V2), and the query with MeSH terms only (V3). These 3 queries were compared with each other based on their sensitivity and positive predictive values. In total, 59 SRs were included. The suppression of MeSH terms had an impact on the number of relevant articles retrieved for 24 (41%) out of 59 SRs. The median (IQR) sensitivities of queries V1 and V2 were 77.8% (62.1%-95.2%) and 71.4% (42.6%-90%), respectively. V1 queries provided an average of 2.62 additional relevant papers per SR compared with V2 queries. However, an additional 820.29 papers had to be screened. The cost of screening an additional collected paper was therefore 313.09, which was slightly more than triple the mean reading cost associated with V2 queries (88.67). Our results revealed that removing MeSH terms from a query decreases sensitivity while slightly increasing the positive predictive value. Queries containing both MeSH and free-text terms yielded more relevant articles but required screening many additional papers. Despite this additional workload, MeSH terms remain indispensable for SRs.

Abstract PR017: Anti-metastatic immunotherapy discovery using ex vivo lung tissue cultures and high-throughput single-cell chemical transcriptomics

Abstract Introduction: Tumors systemically remodel the immune system during metastasis. Developing anti-metastatic immunotherapies that target these tumor-immune interactions to make the metastatic niche hostile colonization would represent a paradigm shift in cancer treatment. However, traditional high-throughput screening (HTS) platforms that use simple read-outs and contrived in vitro systems are ill-suited to identify such therapies. In contrast, HTS platforms that accurately model the metastatic niche and use high-dimensional read-outs such as multiplexed single-cell RNA-sequencing (scRNA-seq) can accurately profile nuanced perturbation responses in individual immune cell types and therefore have the potential to discover anti-metastatic immunotherapies. In this study, we describe the development of an ex vivo lung tissue culture HTS platform that preserves immune gene expression signatures observed in the in vivo metastatic niche and is amenable to single-cell chemical transcriptomic analysis using MULTI- seq (McGinnis et al., Nature Methods, 2019). Inspired by our recent description of myeloid cell TLR-NFκB inflammation during breast cancer lung metastasis (McGinnis et al., Cancer Cell, 2024), we then performed the first anti-metastatic immunotherapy drug screen and identified TLR-NFκB inhibitors that effectively operate on all desired myeloid cell types in the lung metastatic niche. Methods and Results: Building upon existing techniques for culturing precision-cut lung slices (Wu et al., Journal of Experimental Medicine, 2024) and patient- derived tumor fragments (Voabil et al., Nature Medicine, 2021), we established and optimized an ex vivo lung tissue culture system that enables 48-hour culturing of lung slices isolated from 4T1 tumor-bearing mice. scRNA-seq profiling revealed successful capture of all relevant immune cell types and retention of metastasis-associated gene expression programs (e.g., myeloid TLR-NFκB inflammation and neutrophil degranulation) following culture. We then scaled our platform to address how myeloid cells in the lung metastatic niche respond to perturbations targeting every component of the canonical TLR-NFκB signaling cascade. Cell-type-specific perturbation modeling and quantification of TLR-NFκB signaling inhibition identified compounds that optimally perturb all intended myeloid cell types (e.g., tissue-resident macrophages, neutrophils, and monocytes) and represent prioritized candidates for future in vivo validation studies to assess impact on metastatic disease progression. Conclusions: In this study, we describe the development and application of a novel HTS platform that couples ex vivo lung tissue cultures with single-cell chemical transcriptomics to identify anti-metastatic immunotherapy candidates. We demonstrate how our platform can identify TLR-NFκB signaling inhibitors that optimally operate in the lung metastatic niche, paving the way for future interrogation of additional metastasis-associated immune cell signaling pathways in different disease and tissue backgrounds. Citation Format: Chris McGinnis, Winnie Yao, Ansuman Satpathy. Anti-metastatic immunotherapy discovery using ex vivo lung tissue cultures and high-throughput single-cell chemical transcriptomics [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr PR017.

Launching the Maternal and Neonatal section in the Primary Health Care and Family Medicine journal

Not available.

Answering the "100 Most Important Family Medicine Research Questions" from the 1985 Hames Consortium.

The 1985 Hames Consortium convened family medicine researchers to identify outstanding questions in their practice. In this descriptive review, we collected, codified, and analyzed available literature to describe the availability of evidence to answer these questions. Of 136 total questions, researchers rated 33 questions as not at all answered (24.2%), 49 questions as somewhat answered (36.0%), 37 as mostly answered (27.2%), and 17 as fully answered - will implement in practice (12.5%). Notably, 2 of the categories with the highest number of total questions, community oriented primary care and the value of comprehensive care, had the highest percentage of unanswered questions. The Hames 100 questions and categories themselves demonstrate the values and purpose of family medicine research and can serve as a powerful tool to discuss the future of family medicine research. The varied questions illustrate the broad scope of interest of family physicians in 1985, which remains just as relevant today. Our findings indicate that relatively few questions were fully answered, with even fewer questions answered in family medicine journals.

Amyloid Imaging Update: How the Amyloid Landscape Is Changing in Light of the Recent Food and Drug Administration Approval of Antiamyloid Therapeutics.

It has been some time since the Journal of Nuclear Medicine and Technology has published an article on best practices in amyloid imaging. In light of the recent Food and Drug Administration approval of new antiamyloid therapies (AATs) to decrease amyloid plaques in the brain and slow progression of mild cognitive impairment, and the potential increase in the number of amyloid PET scans being acquired to document amyloid plaques, the Journal of Nuclear Medicine and Technology felt it was a perfect time to publish a refresher on best practices. AATs are administered to help slow progression of mild cognitive impairment, allowing patients to live independently a little longer before having to give up their independence and move in with family or into an assisted living facility. Neurologists prescribing AATs must first document that the patient has amyloid plaques. To do this, amyloid PET can be performed, or a lumbar puncture can be used to look for amyloid plaques in the cerebrospinal fluid. Although the latter is more cost-effective and has no associated radiation exposure, it is highly invasive compared with amyloid PET. High-quality amyloid PET scans interpretated by a trained nuclear medicine physician are the first step and key to providing the dementia expert and patient with accurate information on amyloid status, allowing for the best decisions on patient management.

Omitting Radiotherapy after Breast-Conserving Surgery in Luminal A Breast Cancer: The LUMINA Study.

The modern generation of trials evaluating the role of adjuvant radiation have turned to genomic profiling as a further risk stratification tool. The LUMINA trial by Whelan et al, published in the New England Journal of Medicine, applied Ki67 testing to identify those with luminal A disease and evaluated locoregional outcomes with Breast Conserving Surgery (BCS) and endocrine therapy (ET) alone. This paper was reviewed at the Canadian Association of General Surgeons' "Evidence-Based Reviews in Surgery" (EBRS) webinar series. Here, we present the EBRS panel's methodologic review and clinical commentary. The LUMINA study demonstrated very low rates of Local Recurrence (LR) in low-risk patients with luminal A biologic subtype treated with BCS and ET alone without radiation. While the LUMINA study was rigorously designed and executed, there are significant pragmatic limitations to the implementation of the proposed approach using their protocol. We advocate that there is no "one size fits all" approach to early ER+ breast cancer. Choice of treatment strategy should strongly consider patient goals and preferences, with need for incorporation of Quality of Life and patient-reported endpoints into future studies evaluating this population to help guide these nuanced decisions.

RETRACTION: MiR-129-5p Inhibits Glioma Cell Progression InVitro and InVivo by Targeting TGIF2.

Y. Diao, B. Jin, L. Huang, and W. Zhou, "MiR-129-5p Inhibits Glioma Cell Progression InVitro and InVivo by Targeting TGIF2," Journal of Cellular and Molecular Medicine 22, no. 4 (2018): 2357-2367. doi: 10.1111/jcmm.13529. The above article, published online on 12 February 2018 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Stefan Constantinescu; The Foundation for Cellular and Molecular Medicine; and John Wiley and Sons Ltd. The retraction has been agreed following an investigation into concerns raised by a third party, which revealed inappropriate duplications of image panels (Figure4A and 6G) between this and other articles that were either previously published or published later in the same year by different group of authors. Thus, the editors consider the conclusions of this manuscript substantially compromised. The authors and their institute were informed of the concerns and the decision to retract but they remained unresponsive.

Open science practices among authors published in complementary, alternative, and integrative medicine journals: An international, cross-sectional survey.

Open science practices aim to increase transparency in research and increase research availability through open data, open access platforms, and public access. Due to the increasing popularity of complementary, alternative, and integrative medicine (CAIM) research, our study aims to explore current open science practices and perceived barriers among CAIM researchers in their own respective research articles. We conducted an international cross-sectional online survey that was sent to authors that published articles in MEDLINE-indexed journals categorized under the broad subject of "Complementary Therapies" or articles indexed under the MeSH term "Complementary Therapies." Articles were extracted to obtain the names and emails of all corresponding authors. Eight thousand seven hundred eighty-six researchers were emailed our survey, which included questions regarding participants' familiarity with open science practices, their open science practices, and perceived barriers to open science in CAIM with respect to participants' most recently published article. Basic descriptive statistics was generated based on the quantitative data. The survey was completed by 292 participants (3.32% response rate). Results indicate that the majority of participants were "very familiar" (n = 83, 31.68%) or "moderately familiar" (n = 83, 31.68%) with the concept of open science practices while creating their study. Open access publishing was the most familiar to participants, with 51.96% (n = 136) of survey respondents publishing with open access. Despite participants being familiar with other open science practices, the actual implementation of these practices was low. Common barriers participants experienced in implementing open science practices include not knowing where to share the study materials, where to share the data, or not knowing how to make a preprint. Although participants responded that they were familiar with the concept of open science practices, the actual implementation and uses of these practices were low. Barriers included a lack of overall knowledge about open science, and an overall lack of funding or institutional support. Future efforts should aim to explore how to implement methods to improve open science training for CAIM researchers.

Research Methodology Matters: A Comment on the Newly Published Article in the Journal of Evidence-Based Medicine

Research Methodology Matters: A Comment on the Newly Published Article in the Journal of Evidence-Based Medicine

Editors' Picks: Top 10 Diversity, Equity, Inclusion, and Antiracism Papers in Family Medicine Journals.

Physicians within the family medicine workforce are the most diverse compared to other medical specialties in both primarily clinical and academic settings. Family physicians also provide care to the most diverse patients and communities across the United States. As such, research and scholarly work from family physicians on diversity, equity, inclusion, and antiracism (DEIA) can be incredibly impactful. Yet many practicing and teaching physicians are unaware of their colleagues' scholarly DEIA work, which aims to elucidate inequities and barriers to optimal care and, importantly, to educate on ways physicians and learners can recognize and address specific needs of patients and communities marginalized by health care policies and practices. In collaboration with editors from several family medicine journals, the authors move beyond the traditional editorial space to share recent practice-changing and innovative articles, adding voice and momentum to improve DEIA efforts in all spaces where the practice and teaching of family medicine exists.

The recent history and near future of digital health in the field of behavioral medicine: an update on progress from 2019 to 2024.

The field of behavioral medicine has a long and successful history of leveraging digital health tools to promote health behavior change. Our 2019 summary of the history and future of digital health in behavioral medicine (Arigo in J Behav Med 8: 67-83, 2019) was one of the most highly cited articles in the Journal of Behavioral Medicine from 2010 to 2020; here, we provide an update on the opportunities and challenges we identified in 2019. We address the impact of the COVID-19 pandemic on behavioral medicine research and practice and highlight some of the digital health advances it prompted. We also describe emerging challenges and opportunities in the evolving ecosystem of digital health in the field of behavioral medicine, including the emergence of new evidence, research methods, and tools to promote health and health behaviors. Specifically, we offer updates on advanced research methods, the science of digital engagement, dissemination and implementation science, and artificial intelligence technologies, including examples of uses in healthcare and behavioral medicine. We also provide recommendations for next steps in these areas with attention to ethics, training, and accessibility considerations. The field of behavioral medicine has made meaningful advances since 2019 and continues to evolve with impressive pace and innovation.

Hickam's Dictum: An Analysis of Multiple Diagnoses.

Hickam's dictum ("a patient can have as many diseases as he damn well pleases") has been touted as a counterargument to Ockham's razor, which enjoins clinicians to seek a single, simple, or unifying diagnosis. Yet the phenomenon of multiple diagnoses has not been formally analyzed. We evaluated multiple diagnoses using three methods of inquiry: (1) a review of 83 case reports; (2) a review of 220 cases from the New England Journal of Medicine; and (3) an online survey of providers' intuitions. Eighty-three published case reports claimed to instantiate Hickam's dictum or violate Ockham's razor. All reported a primary diagnosis that explained the presenting illness, and one or more additional diagnoses which could be classified into four categories: (1) an incidentaloma (n = 21; 25.3%); (2) a pre-existing disease (n = 26; 31.3%); (3) a disease causally linked to the primary diagnosis (n = 33, 39.8%); and (4) a causally unrelated second disease contributing to the acute presentation (n = 3, 3.6%). Among 220 cases from the New England Journal of Medicine, all reported a unifying final diagnosis. In an online survey, 265 respondents recruited using social media evaluated four hypothetical cases with multiple diagnoses representing this categorization scheme. A majority of respondents (79%; 95% CI, 74-84%) chose the case representing category 4 - a coincident, causally unrelated second diagnosis - as the most unlikely or surprising diagnostic combination. Multiple diagnoses commonly occur. However, the majority of the multiple diagnoses we analyzed were causally linked, or represented incidentalomas or known pre-existing diseases. These diagnostic combinations were unsurprising to a majority of surveyed providers. We show that multiple diagnoses can be arranged in a framework that considers time, probability, and causation. This framework reconciles the alleged conflict between Hickam's dictum and Ockham's razor and has greater practical and pedagogical utility.

GDF15 research from bench to bedside

Pre-clinical data suggest that increased circulating growth differentiation factor 15 (GDF15) is a cause of both anorexia/cachexia syndromes and hyperemesis gravidarum in pregnancy, serious conditions with no highly effective treatment. A phase 2 study of a therapeutic GDF15 monoclonal antibody in the New England Journal of Medicine suggests that effective treatment of anorexia/cachexia in cancer may be approaching.