title stringlengths 1 1.19k | keywords stringlengths 0 668 | concept stringlengths 0 909 | paragraph stringlengths 0 61.8k | PMID stringlengths 10 11 |
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Complete raw and unedited blots assembly used to determine PPARα expression. | (1) original and (2) inverted files of the full raw unedited alpha tubulin blot. (3) original and (4) inverted files of the full raw unedited PPAR alpha blot. (5) The uncropped blots with the relevant bands are clearly labeled.Exposing primary cells infected with the alpha variant of SARS-CoV-2 to therapeutic concentra... | PMC9937660 | ||
Metabolic regulators affect COVID-19 severity and progression | To assess the clinical relevance of these findings we collected a total of 3233 cases of confirmed COVID-19 patients admitted to Hadassah and Ichilov Medical Centers between March 2020 to February 2021. A total of 1156 of these patients (35.8%) were registered with in-hospital use of different metabolic regulators ( | PMC9937660 | ||
The host-immune response in hospitalized COVID-19 patients in different metabolic interventions. | INFLAMMATION, DISEASE PROGRESSION | (Reports suggest that severe COVID-19 is characterized by early inflammation, marked by elevated C-reactive protein (CRP) To track disease progression, we followed changes in CRP during the first 21 days of hospitalization. Data were fitted using locally weighted scatterplot smoothing (Lowess) comparing each drug group... | PMC9937660 | |
Pilot study of prospective administration of nanocrystallized fenofibrate in humans with COVID-19 treated with standard-of-care | respiratory deterioration, pneumonia | PNEUMONIA | To further assess the clinical relevance of our findings, we performed an interventional single-arm clinical study in severe, hospitalized COVID-19 patients, who exhibited respiratory deterioration and severe pneumonia (NCT04661930; | PMC9937660 |
Analysis of variant emergence dynamics and distribution during the study period in participants and other hospitalized patients. | VIRUS, DISEASE, DELETION | (Enrolled participants exhibited a higher prevalence of chronic medical conditions compared to other hospitalized patients admitted with severe COVID-19 during the same period and treated under the same standard-of-care, who were used as historical controls (Dynamic changes in serum levels of CRP and NLR, which mark th... | PMC9937660 | |
Discussion | inflammation | INFLAMMATION, VIRUS | Viruses are dependent on host metabolism to obtain macromolecules essential for their lifecycle. While metabolic interventions of host pathways offer promise, the current reliance on animal models and cell lines limits our ability to identify targets for intervention due to critical metabolic and genetic differences be... | PMC9937660 |
Clinical limitations | comorbidity | PATHOLOGY, SARS-COV-2 INFECTION, STILL | While our clinical results are highly encouraging, baseline differences between the groups and lack of randomization must be noted. Therefore, confounding and/or random error cannot be excluded. For instance, the higher comorbidity burden in the fenofibrate group may have conditioned a lower threshold for the initial h... | PMC9937660 |
Acknowledgements | Funding was provided by European Research Council Consolidator Grants OCLD (project no. 681870) and generous gifts from the Nikoh Foundation and the Sam and Rina Frankel Foundation (YN). The interventional study was supported by Abbott (project FENOC0003). The funders had no role in study design, data collection, and i... | PMC9937660 | ||
Additional information | PMC9937660 | |||
Competing interests | Heart Failure, heart failure, NDD | PCT, HEART FAILURE, HEART FAILURE, HEART, EDWARDS | is registered as an investor in a PCT regarding the use of metabolic regulators for COVID. The author has a patent on the use of PPAR agonists to treat COVID. The author has no other competing interests to declare.No competing interests declared.No competing interests declared.has received personal honoraria for statis... | PMC9937660 |
Author contributions | Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Writing – original draft, Project administration, Writing – review and editing.Data curation, Validation, Investigation, Methodology.Investigation.Investigation.Validation, Investigation, Visualization.Resources, Validation, Investigation.Va... | PMC9937660 | ||
Ethics | -20 | Clinical trial registration NCT04661930.Human subjects: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. ... | PMC9937660 | |
Additional files | PMC9937660 | |||
Differentially expressed genes (DEG) analysis in SARS-CoV-2 infected human lung epithelium. | LUNG | (Tab 2) Normal bronchial epithelial cells (Tab 3) Lung Biopsies (Tab 4) Small airway (Tab 5-6) Epithelial cells in bronchial alveolar lavage fluid. (Tab 7) Primer list used for qPCR gene expression validations. | PMC9937660 | |
Observational study descriptive statistics. | COPD | CHRONIC OBSTRUCTIVE PULMONARY DISEASE, COPD, -11 | (Tab 1-8) Characteristics of COVID-19 patients in the cohort. SBP, systolic blood pressure; DBP, diastolic blood pressure; COPD, chronic obstructive pulmonary disease; SpO2, oxygen saturation; ECMO, extracorporeal membrane oxygenation; IQR, interquartile range. Continuous variables were compared with a two-sample t-tes... | PMC9937660 |
International comparative validation cohorts descriptive statistics. | (Tab 1) Comparative Cohort of the Outpatient Lipid Clinics of the University of Bologna and of the Niguarda Hospital in Milan. (A) Characteristics of included patients stratified by lipid-lowering treatment. A cohort of 2,123 patients (M: 48.1%, F: 51.9%) on statins (1,791, mean age 59.2±15.2 years), fenofibrate (220, ... | PMC9937660 | ||
Interventional study descriptive statistics. | obesity, DM, chronic kidney disease, fever, cough, asthma, low immunoinflammatory stress, dyslipidemia, COPD, diabetes | OBESITY, CORONARY HEART DISEASE, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, COPD, ASTHMA, DYSLIPIDEMIA, REGRESSION, HYPERTENSION, CEREBROVASCULAR DISEASE, CHRONIC LIVER DISEASE, DIABETES | (Tab 1) Characteristics of patients compared in the patients in the interventional study 15 Participants who met the inclusion criteria were assigned to intervention with nanocrystallized fenofibrate (TriCor, AbbVie Inc, North Chicago, IL USA) at a dose of 145 mg (1 tablet) once per day. Standard care for severe-hospit... | PMC9937660 |
Strengthening the reporting of observational studies in epidemiology (STROBE) reporting standards used in the observetional studies. | PMC9937660 | |||
Consolidated Standards of Reporting Trials (CONSORT) reporting standards used in the interventional studies. | PMC9937660 | |||
Data availability | Software resources: Our custom Cell Analysis CellProfiler Pipeline is available on The following previously published datasets were used:
| PMC9937660 | ||
References | SARS-CoV-2 infection, toxicity, inflammation, primary lung bronchiole, deaths | VIRUS, SARS-COV-2 INFECTION, INFLAMMATION, DISEASE, VIRAL INFECTION, PATHOGENESIS | In this study, a metabolism-related drug screen showed that fenofibrate reversed lipid accumulation and blocked SARS-CoV-2 replication through a PPARα-dependent mechanism in both α and δ variants. Patients taking fibrates displayed significantly lower markers of inflammation and experienced faster recovery from disease... | PMC9937660 |
Background | T2D, type 2 diabetes | TYPE 2 DIABETES | The objective was to test the efficacy of a scalable, virtually delivered, diabetes-tailored weight management program on glycemic control in adults with type 2 diabetes (T2D). | PMC10079927 |
Methods | This was a single arm, three-site clinical trial. Participants had baseline HbA1c between 7–11% and BMI between 27–50 kg/m | PMC10079927 | ||
Results | Participants ( | PMC10079927 | ||
Conclusions | The scalable, virtually delivered T2D-tailored weight management program had favorable and clinically meaningful effects on glycemic control, body weight, and psychosocial outcomes. | PMC10079927 | ||
Subject terms | PMC10079927 | |||
Introduction | T2D, Diabetes | DISEASE, TYPE 2 DIABETES, DIABETES | Diabetes is a debilitating, deadly, and costly disease [The American Diabetes Association (ADA) Standards of Care underscore the multiple benefits of weight management in the effective management of type 2 diabetes (T2D) [While clinic-based lifestyle interventions that reduce both weight and HbA1c are the most studied ... | PMC10079927 |
Methods | T2D | This single-arm, three-site trial included Pennington Biomedical Research Center in Baton Rouge, LA, University of Florida in Gainesville, FL, and Virginia Commonwealth University in Richmond, VA. All participants were given verbal and written explanations about the study, provided written informed consent, and receive... | PMC10079927 | |
Statistical analyses | SECONDARY | Analyses adhered to the intent-to-treat principle; missing data were accounted for using maximum likelihood estimation. General linear mixed effect models adjusted for sex were used to evaluate changes over time in HbA1c and secondary outcomes (including percent change) at baseline, 12, and 24 weeks. Results are presen... | PMC10079927 | |
Power calculation | T2D | The sample size calculation was based on a previous WW study with T2D participants that found a 0.6 ± 1.4% decrease in HbA1c at 6 months [ | PMC10079927 | |
Results | The flow of participants from initial screening through week 24 is shown in Fig. | PMC10079927 | ||
Discussion | weight loss, diabetes distress, diabetes | DIABETES | The WW virtual weight loss and wellness program tailored for diabetes resulted in HbA1c reductions and improvements in diabetes distress similar to in-person trials [ | PMC10079927 |
Limitations | weight loss | REGRESSION | These promising results await replication in a randomized controlled trial. While it is possible that the observed effects were simply a regression to the mean, the baseline A1c of <8 suggest this is less likely. It is also unlikely that a nearly 6% weight loss occurs spontaneously in the absence of a structured weight... | PMC10079927 |
Acknowledgements | We are grateful for the PBRC cores including intervention resources (IR), clinical chemistry, and medical records for assisting with the completion of this work. | PMC10079927 | ||
Author contributions | TB | JWA, JGL, SDA, FLG, TB, and GDF contributed to the development of the study concept and design. All authors contributed to data acquisition and interpretation. RAB performed the analysis. JWA and MIC contributed to drafting of the manuscript. All authors contributed to critical revision of the manuscript of important i... | PMC10079927 | |
Funding | This work was funded by WW International, Inc. | PMC10079927 | ||
Competing interests | JWA: Grants NIH NIDDK and NIMHD, NSF, and USDA. JGL: Grants NIH NIDDK. FLG: Consultant: Ed Med Resources, NovMeta Pharma, GNC, Basic Research, Scientific Advisory Board: Altimune, Pfizer, Nutraceutical Corporation, Stock/stock options: UR Labs, Plensat, Ketogenic Health Systems, Slim Health Nutrition, Energesis, Rejuve... | PMC10079927 | ||
References | PMC10079927 | |||
Purpose | fractures | Tibial shaft spiral fractures and fractures of the distal third of the tibia (AO:42A/B/C and 43A) frequently occur with non-displaced posterior malleolus fractures (PM). This study investigated the hypothesis that plain X-ray is not sufficient for a reliable diagnosis of associated non-displaced PM fractures in tibial ... | PMC10728229 | |
Methods | fractures | 50 X-rays showing 42A/B/C and 43A fractures were evaluated by two groups of physicians, each group was comprised of a resident and a fellowship-trained traumatologist or radiologist. Each group was tasked to make a diagnosis and/or suggest if further imaging was needed. One group was primed with the incidence of PM fra... | PMC10728229 | |
Results | fracture, fractures | Overall, 9.13/25 (SD ± 5.77) PM fractures were diagnosed on X-ray. If the posterior malleolus fracture was named or a CT was requested, the fracture was considered “detected”. With this in mind, 14.8 ± 5.95 posterior malleolus fractures were detected.Significantly more fractures were diagnosed/detected (14 vs. 4.25/25;... | PMC10728229 | |
Conclusion | fractures | Only 17% of PM fractures were identified on plain X-ray and awareness of PM only improved diagnosis by 39%. While experiencing improved accuracy, CT imaging should be included in a comprehensive examination of tibial shaft spiral fractures. | PMC10728229 | |
Level of evidence | II. Diagnostic prospective cohort study. | PMC10728229 | ||
Trail registration number | DRKS00030075. | PMC10728229 | ||
Keywords | Open Access funding enabled and organized by Projekt DEAL. | PMC10728229 | ||
Background | fracture, dislocation, postoperative instability, fractures, Fractures | POST-TRAUMATIC OSTEOARTHRITIS, INTRAOPERATIVE COMPLICATIONS, SECONDARY | Concomitant fractures of the posterior malleolus (PM) typically occur in distal tibia fractures (Arbeitsgemeinschaft für Osteosynthesefragen Classification; AO:43A) and especially in spiral fractures of the tibial shaft (AO:42/43A) with a fracture line extending from proximal-lateral to distal-medial in the anterior–po... | PMC10728229 |
Material and methods | trauma, fracture, fractures, Trauma, Fractures | SECONDARY, PATHOLOGICAL FRACTURES | 50 plain X-rays of patients from the emergency department (ER) of a Level I Trauma Center with tibial shaft fractures (AO:42A/B/C and 43A) were prospectively evaluated by different physicians. 25 of the 50 patients had an additional fracture of the posterior malleolus. To avoid a selection bias, the last 25 patients ad... | PMC10728229 |
Results | fracture, fractures | SENSITIVITY | Overall, an average of 9.13 ± 5.77 of the 25 (36.5%) posterior malleolus fractures were correctly diagnosed. In group 1 (no awareness) 4.25 ± 3.77, in group 2 (increased awareness) 14 ± 0 were diagnosed. This was statistically significant (Sensitivity for detecting additional PM fractures in plain X-rays was 0.17 in gr... | PMC10728229 |
Discussion | trauma, fracture, dislocation, fractures, bimalleolar fractures, Fractures | SECONDARY | The results show that based on plain X-rays only it was not possible to rule out accompanying PM fractures in tibial shaft fractures with certainty. Although increased awareness led to a significant improvement in sensitivity (0.17 vs. 0.56), it was still not possible to achieve the required reliability for responsible... | PMC10728229 |
Conclusion | fracture, fractures | Concomitant fractures of the posterior malleolus in tibial shaft fractures were not reliably detected in plain X-rays, regardless of physicians’ specialty or level of training. Awareness of the frequency of these additional fractures in tibial shaft spiral fractures with a course from proximal-lateral to distal-medial ... | PMC10728229 | |
Abbreviations | ANTERIOR | Anterior–posterior X-rayComputed tomographyEmergency roomMaximumMinimumPosterior MalleolusVersus | PMC10728229 | |
Funding | Open Access funding enabled and organized by Projekt DEAL. | PMC10728229 | ||
Data availability | The datasets used and analysed during the study are available from the corresponding author on reasonable request. | PMC10728229 | ||
Declarations | PMC10728229 | |||
Ethics Committee approval | LUDWIG | Ethics Committee of the Ludwig Maximilians University in Munich. (Project Nr.: 21-0301). | PMC10728229 | |
References | PMC10728229 | |||
Background | The adoption of digital health technologies can improve the quality of care for polypharmacy patients, if the underlying complex implementation mechanisms are better understood. Context effects play a critical role in relation to implementation mechanisms. In primary care research, evidence on the effects of context in... | PMC10294464 | ||
Study aim | This study aims to identify contextual factors relevant to physician behavior and how they might mediate the adoption process. | PMC10294464 | ||
Methods | The physicians who participated in this formative evaluation study ( | PMC10294464 | ||
Results | The key dimensions of a (1) context-mechanism-outcome model were mapped and refined. A (2) latent construct of the physicians’ innovation beliefs related to the effectiveness of polypharmacy management practices was identified. Innovation beliefs play a (3) mediating role between the organizational readiness to impleme... | PMC10294464 | ||
Conclusion | Physician adoption is directly affected by the readiness of primary care organizations for the implementation of change. In addition, the mediation analysis revealed that this relationship is indirectly influenced by primary care physicians’ beliefs regarding the effectiveness of digital innovation. Both individual phy... | PMC10294464 | ||
Supplementary Information | The online version contains supplementary material available at 10.1186/s12875-023-02081-x. | PMC10294464 | ||
Keywords | Open Access funding enabled and organized by Projekt DEAL. | PMC10294464 | ||
Background | The implementation of digital health technologies is expected to improve the quality of care and simplify clinical actions [Research has already been conducted on a number of technology-related factors, including the interoperability of new technologies with existing practice systems [As part of the digital transformat... | PMC10294464 | ||
Theoretical framework | Although it is important to identify influential technology-related factors to analyze the complex implementation mechanisms of a digital innovation, these factors were not sufficient as explanatory variables for our theoretical framework. In our study design, we define complexity in terms of both the different levels ... | PMC10294464 | ||
Barriers and facilitators to adoption | Empirically studied implementation barriers and facilitators found in the initial literature search were categorized as follows:
Meso level: Research on organizational determinants that affect adoption include numerous topics, such as organizational culture; organizational readiness for change; networks and communicati... | PMC10294464 | ||
Context in implementation research: a new approach | In addition to the empirically observed organizational and behavioral determinants, we examined the current state of research on context in implementation research [Context is defined as “the relational and dynamic features that shape the mechanisms through which the intervention operates; context is assumed to be dyna... | PMC10294464 | ||
Methods | CMO | Thus, the paradigm of context in (1) realist approaches is situated scientifically and analytically between positivist and constructivist approaches. The goal is to discover semi-predictable patterns related to contexts, underlying generative mechanisms, and outcomes (CMO), and to develop middle-range theories related ... | PMC10294464 | |
Data collection and research design | CMO | MAY | We collected qualitative data (from May to September 2018) and quantitative data (from November 2019 to January 2020) from primary care physicians who participated in the formative evaluation study of the AdAM project. This formative evaluation study was conducted alongside the stepped-wedge, cRCT in AdAM. In the cRCT ... | PMC10294464 |
Description of the innovation | The digital innovation was implemented in 688 recruited general practices in North Rhine-Westphalia. It was expected to improve prescription quality and safety for adult patients with polypharmacy compared to patients receiving standard care. The innovation included several design components (e.g., a digitalized clinic... | PMC10294464 | ||
Data analysis | CMO | Qualitative data analysis was conducted for two purposes: (1) summarizing content-deductive mapping of the data material with the aim of describing the categories of context, resources, reasoning, and outcome (CMO) and (2) application of the belief elicitation approach through deductive-inductive qualitative content an... | PMC10294464 | |
Hypothesis development: structural equation model | M)Based | Because structural equation modeling focuses on testing of models of hypothesized theoretical relationships, we synthesized the results of our literature review to select theory-based latent constructs with the findings related to the qualitative configurational model (see Fig. Context-mechanism-outcome model for physi... | PMC10294464 | |
Measurement instrument | ’ | The data collected in our survey were used to develop the SEM model. The questionnaire was pre-tested in two stages: in think-aloud interviews (Accordingly, the survey included measurement items for each of the models’ latent constructs: ORIC (organizational readiness for implementing change) [Physicians answered the o... | PMC10294464 | |
Measurements: organizational readiness for implementing change (ORIC) (X) | The nine items used to measure ORIC are adapted from Shea et al. and the validated German version [ | PMC10294464 | ||
Measurements: contextualized innovation effectiveness beliefs (mediator) | Following the realist research approach, the items of the CB construct were developed to measure different components of beliefs regarding the effectiveness of innovation. The empirically observed influence of the context on the reasoning process from the qualitative analyses was included in the scale. The construct in... | PMC10294464 | ||
Measurements: behavioral intention to use (BI) (Y) | Three items are used to measure the behavioral intention to use technology for routinely performed and future work tasks (“I routinely use digital innovation for my work with polypharmacy patients,” “I would like to continue to use digital innovation for my work,” “I have performed many of the routine tasks for my poly... | PMC10294464 | ||
Measurements: covariates | Physician characteristics and structural factors were included as covariates. Physician characteristics included age, gender, and work experience in ambulatory care in full years. Age was categorized into three groups (< 50 years, > 50 years, and > 60 years). Gender was dichotomized into male and female (because no ans... | PMC10294464 | ||
Results | PMC10294464 | |||
Qualitative data | The initial qualitative data collection of the evaluation study was conducted with 27 physicians, of whom 15 were in the intervention group and 12 were in the waitlist control group. A brief summary of the qualitative findings is provided as an overview; details of the qualitative data collection and the COREQ checklis... | PMC10294464 | ||
Psychometric properties of the measurement analysis | MM | To test for unidimensionality, exploratory factor analyses of the individual construct items and their Cronbach alpha reliabilities were first examined. The results of these analyses revealed that all scale items associated with a given construct or subconstruct loaded highly (> 0.70) on a single factor. One item from ... | PMC10294464 | |
Discussion | MINOR | Our overarching research objective was to examine complex implementation mechanisms that may explain variations in behavior-related outcomes, such as the adoption of innovation. To this end, we examined the relations between the three meso- and micro-level factors, organizational readiness for change, contextualized in... | PMC10294464 | |
Practical implications | At the time of data collection, the physicians were using digital innovation for approximately 60% of the patients who could potentially derive benefit from it. This indicates that the application was not yet fully implemented. This observation may have practical implications for developing implementation strategies fo... | PMC10294464 | ||
Strengths and limitations | CMO | The sample consisted of primary care physicians who implemented digital innovation for polypharmacy management. Only physicians who had participated in the study between 2018 and 2020 and were part of the intervention group during that period were included in the data analyses. It is likely that physicians recruited fo... | PMC10294464 | |
Conclusion | Implementation research indicates inconsistent implementation effectiveness, possibly related to the proximal outcomes of the actual implementation behavior during the change processes. This study explored the underlying mechanisms. Empirical confirmation of contextual mechanisms expands the theories regarding the func... | PMC10294464 | ||
Acknowledgements | We acknowledge support for the Article Processing Charge from the DFG (German Research Foundation, 491454339). | PMC10294464 | ||
AdAM Study Group | See Supplementary Information (Additional File | PMC10294464 | ||
Authors’ contributions | SS drafted the manuscript and developed interview guides and questionnaires, supported by UK's knowledge. KIH contributed to the formal analysis. JKN provided conceptual input. BSM critically commented on the manuscript. SS performed the qualitative and quantitative data collection and analyses, developed structural eq... | PMC10294464 | ||
Funding | Open Access funding enabled and organized by Projekt DEAL. This study was funded by the Innovation Fund of the German Federal Joint Committee (grant no 01NVF16006). The funder had no role in the design of the study, collection, analysis or interpretation of data, or in the writing of the manuscript. | PMC10294464 | ||
Availability of data and materials | The datasets generated and analyzed during the current study are not publicly available due to participant consent restricting data use to the research team but are available from the corresponding author on reasonable request. | PMC10294464 | ||
Declarations | PMC10294464 | |||
Ethics approval and consent to participate | Study design and evaluation protocol were approved by the North Rhine Medical Association’s ethics committee (application no. 2017184). No objections were raised to any part of the study. This study processed anonymized data. Participants gave informed consent to participate in the study. All methods were carried out i... | PMC10294464 | ||
Consent for publication | Not applicable. | PMC10294464 | ||
Competing interests | The authors declare no competing interests. | PMC10294464 | ||
References | PMC10294464 | |||
Purpose | hemorrhoids, postoperative pain, Pain | HEMORRHOIDS | Pain and reduced quality of life (QoL) are major subjects of interest after surgery for hemorrhoids. The aim of this study was to find predictive parameters for postoperative pain and QoL after hemorrhoidectomy. | PMC10622377 |
Methods | NRS, tamponade, pain | This is a follow-up analysis of data derived from a multicenter randomized controlled trial including 770 patients, which examines the usefulness of tamponade after hemorrhoidectomy. Different pre-, intra-, and postoperative parameters were correlated with pain level assessed by NRS and QoL by the EuroQuol. | PMC10622377 | |
Results | NRS, pain | At univariate analysis, relevant (NRS > 5/10 pts.) early pain within 48 h after surgery was associated with young age (≤ 40 years, | PMC10622377 | |
Conclusion | pain | Early relevant pain affects younger patients but can be prevented by avoiding tamponades and using a pudendal block. Relevant pain after 1 week is associated only with early pain. Relief in preexisting pain and opioids improve QoL. | PMC10622377 | |
Trial registration | DRKS00011590 12 April 2017. | PMC10622377 | ||
Keywords | Open Access funding enabled and organized by Projekt DEAL. | PMC10622377 |
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