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Journal = JCM
Section = Clinical Research Methods

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12 pages, 242 KiB  
Review
Large Language Model Prompting Techniques for Advancement in Clinical Medicine
by Krish Shah, Andrew Y. Xu, Yatharth Sharma, Mohammed Daher, Christopher McDonald, Bassel G. Diebo and Alan H. Daniels
J. Clin. Med. 2024, 13(17), 5101; https://doi.org/10.3390/jcm13175101 - 28 Aug 2024
Cited by 1 | Viewed by 1440
Abstract
Large Language Models (LLMs have the potential to revolutionize clinical medicine by enhancing healthcare access, diagnosis, surgical planning, and education. However, their utilization requires careful, prompt engineering to mitigate challenges like hallucinations and biases. Proper utilization of LLMs involves understanding foundational concepts such [...] Read more.
Large Language Models (LLMs have the potential to revolutionize clinical medicine by enhancing healthcare access, diagnosis, surgical planning, and education. However, their utilization requires careful, prompt engineering to mitigate challenges like hallucinations and biases. Proper utilization of LLMs involves understanding foundational concepts such as tokenization, embeddings, and attention mechanisms, alongside strategic prompting techniques to ensure accurate outputs. For innovative healthcare solutions, it is essential to maintain ongoing collaboration between AI technology and medical professionals. Ethical considerations, including data security and bias mitigation, are critical to their application. By leveraging LLMs as supplementary resources in research and education, we can enhance learning and support knowledge-based inquiries, ultimately advancing the quality and accessibility of medical care. Continued research and development are necessary to fully realize the potential of LLMs in transforming healthcare. Full article
(This article belongs to the Section Clinical Research Methods)
14 pages, 752 KiB  
Review
Methodological and Statistical Considerations for Cross-Sectional, Case–Control, and Cohort Studies
by Edsaúl Emilio Pérez-Guerrero, Miryam Rosario Guillén-Medina, Fabiola Márquez-Sandoval, José María Vera-Cruz, Martha Patricia Gallegos-Arreola, Manuel Alejandro Rico-Méndez, José Alonso Aguilar-Velázquez and Itzae Adonai Gutiérrez-Hurtado
J. Clin. Med. 2024, 13(14), 4005; https://doi.org/10.3390/jcm13144005 - 9 Jul 2024
Cited by 1 | Viewed by 3557
Abstract
Epidemiological studies are essential in medicine and public health as they help identify risk factors and causes of diseases. Additionally, they are key to planning, implementing, and evaluating health interventions aimed at preventing and controlling the spread of diseases. Among these studies, analytical [...] Read more.
Epidemiological studies are essential in medicine and public health as they help identify risk factors and causes of diseases. Additionally, they are key to planning, implementing, and evaluating health interventions aimed at preventing and controlling the spread of diseases. Among these studies, analytical observational studies, such as cross-sectional, case–control, and cohort studies, are the most used. The validity of their results largely depends on the robustness of the design, execution, and statistical analysis. Objective: The objective of this study is to examine the most common errors in the selection of methodological design and statistical tests in analytical observational studies and to provide recommendations to correct them. Methodology: A comprehensive review of the available literature on methodology in epidemiological observational studies was conducted, focusing on cross-sectional, case–control, and cohort studies. Common errors in the selection of designs and statistical tests were identified and analyzed. Results and Conclusions: Errors in the selection of methodological design and statistical tests are common in epidemiological observational studies. Based on the identified errors, a series of recommendations is provided to improve the selection of methodological design and statistical tests, thereby increasing the reliability of the results in cross-sectional, case–control, and cohort studies. Full article
(This article belongs to the Section Clinical Research Methods)
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10 pages, 360 KiB  
Article
Mediation Analysis of Racial Disparity for Infant Mortality Using Bayesian Estimation of Potential Outcomes
by James Thompson
J. Clin. Med. 2024, 13(12), 3464; https://doi.org/10.3390/jcm13123464 - 13 Jun 2024
Viewed by 822
Abstract
Background/Objectives: While the overall rate of infant mortality in the United States has been decreasing over decades, the racial disparity, defined as the difference between races, has increased. Even though a person’s race cannot change, it may be possible to identify factors [...] Read more.
Background/Objectives: While the overall rate of infant mortality in the United States has been decreasing over decades, the racial disparity, defined as the difference between races, has increased. Even though a person’s race cannot change, it may be possible to identify factors that mediate or cause this racial disparity. Evaluating the factors that mediate or cause racial disparity is imperative because current clinical recommendations could be based on preventative modalities that are more effective for white women and their children. Methods: A Bayesian approach modeled the data from the full United States National Natality Database for the years 2016 to 2018. The binomial rate parameters for each combination of race and mediators provided the potential outcomes. Estimating the mediation outcomes, including total effect, controlled direct effect, mediated effect, and proportion mediated used common counterfactual definitions for these probabilities. Results: Maternal smoking, low birthweight, and teenage maternity interacted in causing racial disparity for infant mortality. The proportion of racial disparity attributable to low birthweight was approximately 0.73, with only small variations attributable to maternal smoking and teenage maternity. Conclusions: The novel approach facilitated modeling of multiple mediators. Low birthweight caused racial disparity for infant mortality. The model can be extended to evaluate additional mediational factors with the objective of identifying the preventable causes. Full article
(This article belongs to the Section Clinical Research Methods)
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21 pages, 1641 KiB  
Article
A Real-World Investigation of MRI Changes in Bone in Patients with Type 1 Gaucher Disease Treated with Velaglucerase Alfa: The EIROS Study
by Monia Bengherbia, Marc Berger, Bénédicte Hivert, Florian Rigaudier, Luc Bracoud, Ole Vaeterlein, Karima Yousfi, Michele Maric, Marie Malcles and Nadia Belmatoug
J. Clin. Med. 2024, 13(10), 2926; https://doi.org/10.3390/jcm13102926 - 16 May 2024
Viewed by 1175
Abstract
Background/Objectives: Gaucher disease type 1 (GD1) is characterized by hepatosplenomegaly, thrombocytopenia, and disabling bone manifestations requiring regular MRI monitoring. The EIROS study assessed the real-world impact of velaglucerase alfa on GD1 bone disease, using MRI data collected in French clinical practice. Methods [...] Read more.
Background/Objectives: Gaucher disease type 1 (GD1) is characterized by hepatosplenomegaly, thrombocytopenia, and disabling bone manifestations requiring regular MRI monitoring. The EIROS study assessed the real-world impact of velaglucerase alfa on GD1 bone disease, using MRI data collected in French clinical practice. Methods: MRIs collected retrospectively from treatment initiation and prospectively during follow-up (12-months) were analyzed centrally by a blinded expert radiologist to evaluate bone infiltration using the Bone Marrow Burden (BMB) score and a qualitative method (stable, improved or worsened for the spine and femur). Abdominal MRIs were also centrally analyzed to assess hepatosplenomegaly. Bone manifestations, hepatosplenomegaly, and hematologic parameters were analyzed from medical records. Results: MRI data were available for 20 patients: 6 treatment-naive patients and 14 patients who switched to velaglucerase alfa from another GD treatment. Interpretable MRIs for BMB scoring were available for seven patients for the spine and one patient for the femur. Qualitative assessments (n = 18) revealed stability in spine and femur infiltration in 100.0% and 84.6% of treatment-switched patients (n = 13), respectively, and improvements in 80.0% and 60.0% of treatment-naive patients (n = 5), respectively; no worsening of bone infiltration was observed. Liver, spleen, and hematologic parameters improved in treatment-naive patients and remained stable in treatment-switched patients. Conclusions: The qualitative real-world data support findings from clinical trials suggesting the long-term effectiveness of velaglucerase alfa on GD1 bone manifestations. When MRI assessment by radiologists with experience of GD is not possible, a simplified qualitative assessment may be sufficient in clinical practice for monitoring bone disease progression and treatment response. Full article
(This article belongs to the Section Clinical Research Methods)
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10 pages, 463 KiB  
Article
Inpatient Outcomes of Patients Undergoing Robot-Assisted versus Laparoscopic Radical Cystectomy for Bladder Cancer: A National Inpatient Sample Database Study
by Le-Wei Fan, Yun-Ren Li, Cheng-Mu Wu, Kai-Ti Chuang, Wei-Chang Li, Chung-Yi Liu and Ying-Hsu Chang
J. Clin. Med. 2024, 13(3), 772; https://doi.org/10.3390/jcm13030772 - 29 Jan 2024
Viewed by 1070
Abstract
Background: Bladder cancer is a common urinary tract malignancy. Minimally invasive radical cystectomy has shown oncological outcomes comparable to the conventional open surgery and with advantages over the open procedure. However, outcomes of the two main minimally invasive procedures, robot-assisted and pure laparoscopic, [...] Read more.
Background: Bladder cancer is a common urinary tract malignancy. Minimally invasive radical cystectomy has shown oncological outcomes comparable to the conventional open surgery and with advantages over the open procedure. However, outcomes of the two main minimally invasive procedures, robot-assisted and pure laparoscopic, have yet to be compared. This study aimed to compare in-hospital outcomes between these two techniques performed for patients with bladder cancer. Methods: This population-based, retrospective study included hospitalized patients aged ≥ 50 years with a primary diagnosis of bladder cancer who underwent robot-assisted or pure laparoscopic radical cystectomy. All patient data were extracted from the US National Inpatient Sample (NIS) database 2008–2018 and were analyzed retrospectively. Primary outcomes were in-hospital mortality, prolonged length of stay (LOS), and postoperative complications. Results: The data of 3284 inpatients (representing 16,288 US inpatients) were analyzed. After adjusting for confounders, multivariable analysis revealed that patients who underwent robot-assisted radical cystectomy had a significantly lower risk of in-hospital mortality (adjusted OR [aOR], 0.50, 95% CI: 0.28–0.90) and prolonged LOS (aOR, 0.63, 95% CI: 0.49–0.80) than those undergoing pure laparoscopic cystectomy. Patients who underwent robot-assisted radical cystectomy had a lower risk of postoperative complications (aOR, 0.69, 95% CI: 0.54–0.88), including bleeding (aOR, 0.73, 95% CI: 0.54–0.99), pneumonia (aOR, 0.49, 95% CI: 0.28–0.86), infection (aOR, 0.55, 95% CI: 0.36–0.85), wound complications (aOR, 0.33, 95% CI: 0.20–0.54), and sepsis (aOR, 0.49, 95% CI: 0.34–0.69) compared to those receiving pure laparoscopic radical cystectomy. Conclusions: Patients with bladder cancer, robot-assisted radical cystectomy is associated with a reduced risk of unfavorable short-term outcomes, including in-hospital mortality, prolonged LOS, and postoperative complications compared to pure laparoscopic radical cystectomy. Full article
(This article belongs to the Section Clinical Research Methods)
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14 pages, 1373 KiB  
Article
Validation of a Wearable Medical Device for Automatic Diagnosis of OSA against Standard PSG
by Jesus Sanchez Gomez, Renard Xaviero Adhi Pramono, Syed Anas Imtiaz, Esther Rodriguez-Villegas and Agustin Valido Morales
J. Clin. Med. 2024, 13(2), 571; https://doi.org/10.3390/jcm13020571 - 19 Jan 2024
Cited by 3 | Viewed by 1781
Abstract
Study objective: The objective of this study was to assess the accuracy of automatic diagnosis of obstructive sleep apnea (OSA) with a new, small, acoustic-based, wearable technology (AcuPebble SA100), by comparing it with standard type 1 polysomnography (PSG) diagnosis. Material and methods: This [...] Read more.
Study objective: The objective of this study was to assess the accuracy of automatic diagnosis of obstructive sleep apnea (OSA) with a new, small, acoustic-based, wearable technology (AcuPebble SA100), by comparing it with standard type 1 polysomnography (PSG) diagnosis. Material and methods: This observational, prospective study was carried out in a Spanish hospital sleep apnea center. Consecutive subjects who had been referred to the hospital following primary care suspicion of OSA were recruited and underwent in-laboratory attended PSG, together with the AcuPebble SA100 device simultaneously overnight from January to December 2022. Results: A total of 80 patients were recruited for the trial. The patients had a median Epworth scoring of 10, a mean of 10.4, and a range of 0–24. The mean AHI obtained with PSG plus sleep clinician marking was 23.2, median 14.3 and range 0–108. The study demonstrated a diagnostic accuracy (based on AHI) of 95.24%, sensitivity of 92.86%, specificity of 97.14%, positive predictive value of 96.30%, negative predictive value of 94.44%, positive likelihood ratio of 32.50 and negative likelihood ratio of 0.07. Conclusions: The AcuPebble SA100 (EU) device has demonstrated an accurate automated diagnosis of OSA in patients undergoing in-clinic sleep testing when compared against the gold-standard reference of in-clinic PSG. Full article
(This article belongs to the Section Clinical Research Methods)
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8 pages, 224 KiB  
Article
Comparison of Manual versus Automated SARS-CoV-2 Rapid Antigen Testing in Asymptomatic Individuals
by David T. Harris, Nicole Ingraham and Michael Badowski
J. Clin. Med. 2023, 12(22), 7146; https://doi.org/10.3390/jcm12227146 - 17 Nov 2023
Viewed by 830
Abstract
The SARS-CoV-2 pandemic has infected more than 770 M people and killed more than 6.9 M persons worldwide. In the USA, as of August 2023, it has infected more than 103 M people while causing more than 1.1 M deaths. During a pandemic, [...] Read more.
The SARS-CoV-2 pandemic has infected more than 770 M people and killed more than 6.9 M persons worldwide. In the USA, as of August 2023, it has infected more than 103 M people while causing more than 1.1 M deaths. During a pandemic, it is necessary to rapidly identify those individuals infected with the virus so that disease transmission can be stopped. We examined the sensitivity of the Quidel Rapid Antigen test on the manual Sofia 2 platform and the Beckman-Coulter antigen test on the automated DxI-800 system for use in screening asymptomatic individuals at the University of Arizona from March through May 2021. A total of 378 asymptomatic subjects along with 176 validation sets of samples in 23 independent experiments were assessed in side-by-side antigen testing using both assays. Nasal swabs and saliva were used as viral sources. Manual testing (Quidel) was compared with automated testing (Beckman) methods for cost and efficiency. Limit dilution of viral antigen spiked samples was performed to determine sensitivity to antigen load by the tests. The results between the two tests were found to be concordant. Both tests were comparable in terms of detecting low numbers of positive subjects in the asymptomatic population. A concordance of 98% was observed between the two tests. Experiments also demonstrated that saliva specimens were an acceptable viral source and produced comparable results for each test. Overall, the two methods were interchangeable. Full article
(This article belongs to the Section Clinical Research Methods)
10 pages, 453 KiB  
Review
It’s Time to Go Quantum in Medicine
by Joseph Bisiani, Adith Anugu and Srinivas Pentyala
J. Clin. Med. 2023, 12(13), 4506; https://doi.org/10.3390/jcm12134506 - 5 Jul 2023
Cited by 5 | Viewed by 5725
Abstract
As the field of medicine grows and expands, new scientific developments hold great promise for improving quality of care, clinical research, and the diagnosis and treatment of diseases. Quantum physics is a promising field that intersects with medicine much more than originally understood. [...] Read more.
As the field of medicine grows and expands, new scientific developments hold great promise for improving quality of care, clinical research, and the diagnosis and treatment of diseases. Quantum physics is a promising field that intersects with medicine much more than originally understood. In terms of diagnosing different diseases, incorporating quantum mechanics into the study of medicine can allow for efficient diagnosis before symptoms even arise in a patient. Applying theory-based mathematical structures that describe neuron transmission throughout the brain and mind on a quantum scale can help us to better understand neurological diseases in patients. Quantum theory can even give plausible explanations for subtle DNA changes and even telomere reduction in patients who develop cancer. Utilizing quantum theory in the field of medicine can help in understanding and applying treatments for a multitude of different diseases, such as Alzheimer’s disease or diverse types of cancer, and even expand upon efficient and reliable diagnosis in clinical settings. Quantum physics is a pertinent advancing field that may have a significant impact on expanding medical care and treatment in the near future. In this review, the application of quantum physics in medicine is discussed. Full article
(This article belongs to the Section Clinical Research Methods)
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18 pages, 290 KiB  
Article
Development of a Visuoperceptual Measure for Fiberoptic Endoscopic Evaluation of Swallowing (V-FEES) in Adults with Oropharyngeal Dysphagia: An International Delphi Study
by Reinie Cordier, Renée Speyer, Susan Langmore, Deborah Denman, Katina Swan and Daniele Farneti
J. Clin. Med. 2023, 12(12), 3875; https://doi.org/10.3390/jcm12123875 - 6 Jun 2023
Viewed by 1424
Abstract
Visuoperceptual evaluation of fiberoptic endoscopic evaluation of swallowing (FEES) is a commonly used assessment in dysphagia or swallowing disorders. Currently, no international consensus exists regarding which visuoperceptual measures to use for the analysis of FEES recordings. Moreover, existing visuoperceptual FEES measures are limited [...] Read more.
Visuoperceptual evaluation of fiberoptic endoscopic evaluation of swallowing (FEES) is a commonly used assessment in dysphagia or swallowing disorders. Currently, no international consensus exists regarding which visuoperceptual measures to use for the analysis of FEES recordings. Moreover, existing visuoperceptual FEES measures are limited by poor and incomplete psychometric data, identifying an urgent need for developing a visuoperceptual measure to interpret FEES recordings. Following the COSMIN group’s (COnsensus-based Standards for the selection of health Measurement INstruments) psychometric taxonomy and guidelines, this study aimed to establish the content validity of a new visuoperceptual FEES (V-FEES) measure in adults with oropharyngeal dysphagia. Using the Delphi technique, international consensus was achieved among dysphagia experts across 21 countries, resulting in a new prototype measure for V-FEES, comprising 30 items, 8 function testing items (i.e., specific tasks performed by patients while observing and rating items), and 36 unique operationalisations (i.e., defining items into measurable factors that could be measured empirically using visuoperceptual observation). This study supports good content validity for V-FEES, including participants’ feedback on the relevance, comprehensiveness, and comprehensibility of the included items. Future studies will continue the instrument development process and determine the remaining psychometric properties using both the classic test theory (CTT) and item response theory (IRT) models. Full article
(This article belongs to the Section Clinical Research Methods)
11 pages, 255 KiB  
Article
Assessment of the Utilization of Validated Diagnostic Predictive Tools and D-Dimer in the Evaluation of Pulmonary Embolism: A Single-Center Retrospective Cohort Study from a Public Hospital in New York City
by Amrin Kharawala, Jiyoung Seo, Diego Barzallo, Gabriel Hernandez Romero, Yunus Emre Demirhan, Gustavo J. Duarte, Charan Thej Reddy Vegivinti, Manuel Hache-Marliere, Prasanth Balasubramanian, Heitor Tavares Santos, Sanjana Nagraj, Majd Al Deen Alhuarrat, Dimitrios Karamanis, Dimitrios Varrias and Leonidas Palaiodimos
J. Clin. Med. 2023, 12(11), 3629; https://doi.org/10.3390/jcm12113629 - 23 May 2023
Cited by 3 | Viewed by 2304
Abstract
Introduction: A significant increase in the use of computed tomography with pulmonary angiography (CTPA) for the diagnosis of pulmonary embolism (PE) has been observed in the past twenty years. We aimed to investigate whether the validated diagnostic predictive tools and D-dimers were adequately [...] Read more.
Introduction: A significant increase in the use of computed tomography with pulmonary angiography (CTPA) for the diagnosis of pulmonary embolism (PE) has been observed in the past twenty years. We aimed to investigate whether the validated diagnostic predictive tools and D-dimers were adequately utilized in a large public hospital in New York City. Methods: We conducted a retrospective review of patients who underwent CTPA for the specific indication of ruling out PE over a period of one year. Two independent reviewers, blinded to each other and to the CTPA and D-dimer results, estimated the clinical probability (CP) of PE using Well’s score, the YEARS algorithm, and the revised Geneva score. Patients were classified based on the presence or absence of PE in the CTPA. Results: A total of 917 patients were included in the analysis (median age: 57 years, female: 59%). The clinical probability of PE was considered low by both independent reviewers in 563 (61.4%), 487 (55%), and 184 (20.1%) patients based on Well’s score, the YEARS algorithm, and the revised Geneva score, respectively. D-dimer testing was conducted in less than half of the patients who were deemed to have low CP for PE by both independent reviewers. Using a D-dimer cut-off of <500 ng/mL or the age-adjusted cut-off in patients with a low CP of PE would have missed only a small number of mainly subsegmental PE. All three tools, when combined with D-dimer < 500 ng/mL or <age-adjusted cut-off, yielded a NPV of > 95%. Conclusion: All three validated diagnostic predictive tools were found to have significant diagnostic value in ruling out PE when combined with a D-dimer cut-off of <500 ng/mL or the age-adjusted cut-off. Excessive use of CTPA was likely secondary to suboptimal use of diagnostic predictive tools. Full article
(This article belongs to the Section Clinical Research Methods)
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16 pages, 482 KiB  
Opinion
When Characteristics of Clinical Trials Require Per-Protocol as Well as Intention-to-Treat Outcomes to Draw Reliable Conclusions: Three Examples
by David E. Scheim, Colleen Aldous, Barbara Osimani, Edmund J. Fordham and Wendy E. Hoy
J. Clin. Med. 2023, 12(11), 3625; https://doi.org/10.3390/jcm12113625 - 23 May 2023
Cited by 4 | Viewed by 4865
Abstract
Under exceptional circumstances, including high rates of protocol non-compliance, per-protocol (PP) analysis can better indicate the real-world benefits of a medical intervention than intention-to-treat (ITT) analysis. Exemplifying this, the first randomized clinical trial (RCT) considered found that colonoscopy screenings were marginally beneficial, based [...] Read more.
Under exceptional circumstances, including high rates of protocol non-compliance, per-protocol (PP) analysis can better indicate the real-world benefits of a medical intervention than intention-to-treat (ITT) analysis. Exemplifying this, the first randomized clinical trial (RCT) considered found that colonoscopy screenings were marginally beneficial, based upon ITT analysis, with only 42% of the intervention group actually undergoing the procedure. However, the study authors themselves concluded that the medical efficacy of that screening was a 50% reduction in colorectal cancer deaths among that 42% PP group. The second RCT found a ten-fold reduction in mortality for a COVID-19 treatment drug vs. placebo by PP analysis, but only a minor benefit by ITT analysis. The third RCT, conducted as an arm of the same platform trial as the second RCT, tested another COVID-19 treatment drug and reported no significant benefit by ITT analysis. Inconsistencies and irregularities in the reporting of protocol compliance for this study required consideration of PP outcomes for deaths and hospitalizations, yet the study coauthors refused to disclose them, instead directing inquiring scientists to a data repository which never held the study’s data. These three RCTs illustrate conditions under which PP outcomes may differ significantly from ITT outcomes and the need for data transparency when these reported or indicated discrepancies arise. Full article
(This article belongs to the Section Clinical Research Methods)
3 pages, 190 KiB  
Editorial
Simpson’s Paradox in Clinical Research: A Cautionary Tale
by Stefanos Bonovas and Daniele Piovani
J. Clin. Med. 2023, 12(4), 1633; https://doi.org/10.3390/jcm12041633 - 18 Feb 2023
Cited by 9 | Viewed by 2492
Abstract
The word paradox comes from the Greek paradoxon, meaning something that was contrary to, or contradicted, common sense [...] Full article
(This article belongs to the Section Clinical Research Methods)
4 pages, 190 KiB  
Editorial
On p-Values and Statistical Significance
by Stefanos Bonovas and Daniele Piovani
J. Clin. Med. 2023, 12(3), 900; https://doi.org/10.3390/jcm12030900 - 23 Jan 2023
Cited by 10 | Viewed by 5459
Abstract
At the beginning of our research training, we learned about hypothesis testing, p-values, and statistical inference [...] Full article
(This article belongs to the Section Clinical Research Methods)
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