-
JACC. Advances Oct 2023
PubMed: 38938345
DOI: 10.1016/j.jacadv.2023.100627 -
Health Technology Assessment... Jun 2024To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund...
BACKGROUND
To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund antimicrobials based on an evaluation of their value as opposed to the volumes used. The aim of this project was to evaluate the population-level health benefit of cefiderocol in the NHS in England, for the treatment of severe aerobic Gram-negative bacterial infections when used within its licensed indications. The results were used to inform the National Institute for Health and Care Excellence guidance in support of commercial discussions regarding contract value between the manufacturer and NHS England.
METHODS
The health benefit of cefiderocol was first derived for a series of high-value clinical scenarios. These represented uses that were expected to have a significant impact on patients' mortality risks and health-related quality of life. The clinical effectiveness of cefiderocol relative to its comparators was estimated by synthesising evidence on susceptibility of the pathogens of interest to the antimicrobials in a network meta-analysis. Patient-level costs and health outcomes of cefiderocol under various usage scenarios compared with alternative management strategies were quantified using decision modelling. Results were reported as incremental net health effects expressed in quality-adjusted life-years, which were scaled to 20-year population values using infection number forecasts based on data from Public Health England. The outcomes estimated for the high-value clinical scenarios were extrapolated to other expected uses for cefiderocol.
RESULTS
Among isolates with the metallo-beta-lactamase resistance mechanism, the base-case network meta-analysis found that cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.32, 95% credible intervals 0.04 to 2.47), but the result was not statistically significant. The other treatments were also associated with lower susceptibility than colistin, but the results were not statistically significant. In the metallo-beta-lactamase base-case network meta-analysis, cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.44, 95% credible intervals 0.03 to 3.94), but the result was not statistically significant. The other treatments were associated with no susceptibility. In the base case, patient-level benefit of cefiderocol was between 0.02 and 0.15 quality-adjusted life-years, depending on the site of infection, the pathogen and the usage scenario. There was a high degree of uncertainty surrounding the benefits of cefiderocol across all subgroups. There was substantial uncertainty in the number of infections that are suitable for treatment with cefiderocol, so population-level results are presented for a range of scenarios for the current infection numbers, the expected increases in infections over time and rates of emergence of resistance. The population-level benefits varied substantially across the base-case scenarios, from 896 to 3559 quality-adjusted life-years over 20 years.
CONCLUSION
This work has provided quantitative estimates of the value of cefiderocol within its areas of expected usage within the NHS.
LIMITATIONS
Given existing evidence, the estimates of the value of cefiderocol are highly uncertain.
FUTURE WORK
Future evaluations of antimicrobials would benefit from improvements to NHS data linkages; research to support appropriate synthesis of susceptibility studies; and application of routine data and decision modelling to assess enablement value.
STUDY REGISTRATION
No registration of this study was undertaken.
FUNDING
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment Policy Research Programme (NIHR award ref: NIHR135591), conducted through the Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions, PR-PRU-1217-20401, and is published in full in ; Vol. 28, No. 28. See the NIHR Funding and Awards website for further award information.
Topics: Humans; Cephalosporins; Anti-Bacterial Agents; Quality-Adjusted Life Years; Cost-Benefit Analysis; England; Technology Assessment, Biomedical; Cefiderocol; Gram-Negative Bacterial Infections; State Medicine; Quality of Life
PubMed: 38938145
DOI: 10.3310/YGWR4511 -
Journal of Cardiothoracic Surgery Jun 2024Currently, the differentiation between benign and malignant cystic pulmonary nodules poses a significant challenge for clinicians. The objective of this retrospective...
BACKGROUND
Currently, the differentiation between benign and malignant cystic pulmonary nodules poses a significant challenge for clinicians. The objective of this retrospective study was to construct a predictive model for determining the likelihood of malignancy in patients with cystic pulmonary nodules.
METHODS
The current study involved 129 patients diagnosed with cystic pulmonary nodules between January 2017 and June 2023 at the Neijiang First People's Hospital. The study gathered the clinical data, preoperative imaging features of chest CT, and postoperative histopathological results for both cohorts. Univariate and multivariate logistic regression analyses were employed to identify independent risk factors, from which a prediction model and nomogram were developed. In addition, The model's performance was assessed through receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA).
RESULTS
A cohort of 129 patients presenting with cystic pulmonary nodules, consisting of 92 malignant and 37 benign lesions, was examined. Logistic data analysis identified a cystic airspace with a mural nodule, spiculation, mural morphology, and the number of cystic cavities as significant independent predictors for discriminating between benign and malignant cystic lung nodules. The nomogram prediction model demonstrated a high level of predictive accuracy, as evidenced by an area under the ROC curve (AUC) of 0.874 (95% CI: 0.804-0.944). Furthermore, the calibration curve of the model displayed satisfactory calibration. DCA proved that the prediction model was useful for clinical application.
CONCLUSION
In summary, the risk prediction model for benign and malignant cystic pulmonary nodules has the potential to assist clinicians in the diagnosis of such nodules and enhance clinical decision-making processes.
Topics: Humans; Nomograms; Male; Female; Retrospective Studies; Tomography, X-Ray Computed; Middle Aged; Lung Neoplasms; Diagnosis, Differential; Multiple Pulmonary Nodules; Aged; Solitary Pulmonary Nodule; ROC Curve; Adult; Radiomics
PubMed: 38937772
DOI: 10.1186/s13019-024-02936-z -
Parasites & Vectors Jun 2024Mosquitoes are important vectors of pathogens. They are usually collected with CO-baited traps and subsequently identified by morphology. This procedure is very...
BACKGROUND
Mosquitoes are important vectors of pathogens. They are usually collected with CO-baited traps and subsequently identified by morphology. This procedure is very time-consuming. Automatic counting traps could facilitate timely evaluation of the local risk for mosquito-borne pathogen transmission or decision-making on vector control measures, but the counting accuracy of such devices has rarely been validated in the field.
METHODS
The Biogents (BG)-Counter 2 automatically counts mosquitoes by discriminating the size of captured objects directly in the field and transmits the data to a cloud server. To assess the accuracy of this counting device, 27 traps were placed at 19 sampling sites across Germany and used in daily, weekly or bimonthly intervals from April until October 2021. The BG-Counter 2 was attached to a CO-trap (BG-Pro trap = CO-Pro) and the same trap was converted to also attract gravid mosquitoes (upside-down BG-Pro trap with a water container beneath = CO-Pro-gravid). All captured mosquitoes were identified by morphology. The number of females (unfed and gravid), mosquito diversity and the number of identified specimens in relation to the counting data of the BG-Counter were compared between the two trapping devices to evaluate sampling success and counting accuracy.
RESULTS
In total 26,714 mosquitoes were collected during 854 trap days. The CO-Pro-gravid trap captured significantly more mosquitoes per trap day for all specimens, gravid females and non-gravid females, while there was no difference in the mosquito diversity. The linear model with the captured mosquitoes as a response and the counted specimens as a predictor explained only a small degree of the variation within the data (R = 0.16), but per individual trap the value could reach up to 0.62 (mean R = 0.23). The counting accuracy for the daily samples had a significant positive correlation with sample size, resulting in higher accuracy for the CO-Pro-gravid trap and higher accuracy for sites and sampling months with high mosquito abundance.
CONCLUSIONS
While the accuracy of the BG-Counter 2 is quite low, the device is able to depict mosquito phenology and provide information about local population dynamics.
Topics: Animals; Mosquito Control; Mosquito Vectors; Female; Culicidae; Germany
PubMed: 38937756
DOI: 10.1186/s13071-024-06338-x -
Journal of Translational Medicine Jun 2024Over the last two decades, tumor-derived RNA expression signatures have been developed for the two most commonly diagnosed tumors worldwide, namely prostate and breast...
BACKGROUND
Over the last two decades, tumor-derived RNA expression signatures have been developed for the two most commonly diagnosed tumors worldwide, namely prostate and breast tumors, in order to improve both outcome prediction and treatment decision-making. In this context, molecular signatures gained by main components of the tumor microenvironment, such as cancer-associated fibroblasts (CAFs), have been explored as prognostic and therapeutic tools. Nevertheless, a deeper understanding of the significance of CAFs-related gene signatures in breast and prostate cancers still remains to be disclosed.
METHODS
RNA sequencing technology (RNA-seq) was employed to profile and compare the transcriptome of CAFs isolated from patients affected by breast and prostate tumors. The differentially expressed genes (DEGs) characterizing breast and prostate CAFs were intersected with data from public datasets derived from bulk RNA-seq profiles of breast and prostate tumor patients. Pathway enrichment analyses allowed us to appreciate the biological significance of the DEGs. K-means clustering was applied to construct CAFs-related gene signatures specific for breast and prostate cancer and to stratify independent cohorts of patients into high and low gene expression clusters. Kaplan-Meier survival curves and log-rank tests were employed to predict differences in the outcome parameters of the clusters of patients. Decision-tree analysis was used to validate the clustering results and boosting calculations were then employed to improve the results obtained by the decision-tree algorithm.
RESULTS
Data obtained in breast CAFs allowed us to assess a signature that includes 8 genes (ITGA11, THBS1, FN1, EMP1, ITGA2, FYN, SPP1, and EMP2) belonging to pro-metastatic signaling routes, such as the focal adhesion pathway. Survival analyses indicated that the cluster of breast cancer patients showing a high expression of the aforementioned genes displays worse clinical outcomes. Next, we identified a prostate CAFs-related signature that includes 11 genes (IL13RA2, GDF7, IL33, CXCL1, TNFRSF19, CXCL6, LIFR, CXCL5, IL7, TSLP, and TNFSF15) associated with immune responses. A low expression of these genes was predictive of poor survival rates in prostate cancer patients. The results obtained were significantly validated through a two-step approach, based on unsupervised (clustering) and supervised (classification) learning techniques, showing a high prediction accuracy (≥ 90%) in independent RNA-seq cohorts.
CONCLUSION
We identified a huge heterogeneity in the transcriptional profile of CAFs derived from breast and prostate tumors. Of note, the two novel CAFs-related gene signatures might be considered as reliable prognostic indicators and valuable biomarkers for a better management of breast and prostate cancer patients.
Topics: Humans; Prostatic Neoplasms; Male; Breast Neoplasms; Female; Cancer-Associated Fibroblasts; Gene Expression Regulation, Neoplastic; Prognosis; Transcriptome; Gene Expression Profiling; Cluster Analysis; Treatment Outcome; Middle Aged; Kaplan-Meier Estimate
PubMed: 38937754
DOI: 10.1186/s12967-024-05413-2 -
BMC Geriatrics Jun 2024Breast cancer and frailty frequently co-occur in older women, and frailty status has been shown to predict negative health outcomes. However, the extent to which frailty...
BACKGROUND
Breast cancer and frailty frequently co-occur in older women, and frailty status has been shown to predict negative health outcomes. However, the extent to which frailty assessments are utilized in observational research for the older breast cancer population is uncertain. Therefore, the aim of this review was to determine the frequency of use of frailty assessments in studies investigating survival or mortality, and characterize them, concentrating on literature from the past 5 years (2017-2022).
METHODS
MEDLINE, EMBASE and Cochrane Library were systematically queried to identify observational studies (case-control, cohort, cross-sectional) published from 2017-2022 that focus on older females (≥ 65 years) diagnosed with breast cancer, and which evaluate survival or mortality outcomes. Independent reviewers assessed the studies for eligibility using Covidence software. Extracted data included characteristics of each study as well as information on study design, study population, frailty assessments, and related health status assessments. Risk of bias was evaluated using the appropriate JBI tool. Information was cleaned, classified, and tabulated into review level summaries.
RESULTS
In total, 9823 studies were screened for inclusion. One-hundred and thirty studies were included in the final synthesis. Only 11 (8.5%) of these studies made use of a frailty assessment, of which 4 (3.1%) quantified frailty levels in their study population, at baseline. Characterization of frailty assessments demonstrated that there is a large variation in terms of frailty definitions and resulting patient classification (i.e., fit, pre-frail, frail). In the four studies that quantified frailty, the percentage of individuals classified as pre-frail and frail ranged from 18% to 29% and 0.7% to 21%, respectively. Identified frailty assessments included the Balducci score, the Geriatric 8 tool, the Adapted Searle Deficits Accumulation Frailty index, the Faurot Frailty index, and the Mian Deficits of Accumulation Frailty Index, among others. The Charlson Comorbidity Index was the most used alternative health status assessment, employed in 56.9% of all 130 studies. Surprisingly, 31.5% of all studies did not make use of any health status assessments.
CONCLUSION
Few observational studies examining mortality or survival outcomes in older women with breast cancer incorporate frailty assessments. Additionally, there is significant variation in definitions of frailty and classification of patients. While comorbidity assessments were more frequently included, the pivotal role of frailty for patient-centered decision-making in clinical practice, especially regarding treatment effectiveness and tolerance, necessitates more deliberate attention. Addressing this oversight more explicitly could enhance our ability to interpret observational research in older cancer patients.
Topics: Humans; Female; Breast Neoplasms; Frailty; Aged; Observational Studies as Topic; Geriatric Assessment; Frail Elderly; Aged, 80 and over
PubMed: 38937703
DOI: 10.1186/s12877-024-05152-5 -
Scientific Reports Jun 2024Behavioural nudges are often criticised because they "work best in the dark". However, recent experimental evidence suggests that the effectiveness of nudges is not...
Behavioural nudges are often criticised because they "work best in the dark". However, recent experimental evidence suggests that the effectiveness of nudges is not reduced when they are delivered transparently. Most people also endorse transparent nudges. Yet, transparent nudging may undermine human autonomy-a minority may oppose to being nudged and feel manipulated, even if they know what is happening. We propose an alternative way of maintaining autonomy that is not reducible to transparency: individuals can be asked if they consent in advance to being nudged. To assess whether consensual nudges are effective, we ask consent from 1518 UK citizens to be nudged. Subsequently, we default all participants into donating to a charity of their choice, irrespective of self-reported consent. We find that the default nudge is equally effective for both consenting and non-consenting individuals, with negligible difference in average donations. However, non-consenting individuals report higher levels of resentment and regret and lower levels of happiness and support compared to the consenting group. Based on these findings, we argue that ignoring consent can have serious ethical ramifications for policy-making with nudges.
Topics: Humans; Male; Female; Informed Consent; Choice Behavior; Adult; Personal Autonomy; United Kingdom; Middle Aged
PubMed: 38937507
DOI: 10.1038/s41598-024-65122-0 -
Gaceta Sanitaria Jun 2024To examine the presence of women in the organs of the Interterritorial Council of the Spanish National Health System (CISNS).
OBJECTIVE
To examine the presence of women in the organs of the Interterritorial Council of the Spanish National Health System (CISNS).
METHOD
Annual reports of the CISNS from 2005 to 2022 were analyzed. Artificial intelligence was used to assign gender, and percentages of women's participation were calculated. Temporal evolution, vertical segregation, and horizontal segregation were analyzed.
RESULTS
Between 2005 and 2022, there were 14,308 participations in 85 organs, with 52% women, rising from 42% in 2005 to 61% in 2022. There was a higher participation of women in propositional organs (54%), followed by executive ones (50%), and plenary sessions (40%). The General State Administration had 61% women compared to 48% in autonomous communities. Women's participation varied by topic, being higher (82%) in gender violence and lower (35%) in inspection.
CONCLUSIONS
Although there is a slight reduction in the participation gap between women and men, inequalities persist. Women have less presence in higher hierarchical levels (plenary sessions), maintaining vertical segregation. Additionally, women's representation in certain topics remains low, maintaining horizontal segregation. Concrete actions must be taken to continue advancing equality and improving health outcomes in society as a whole.
PubMed: 38936295
DOI: 10.1016/j.gaceta.2024.102406 -
JMIR Bioinformatics and Biotechnology Jun 2024Health care is at a turning point. We are shifting from protocolized medicine to precision medicine, and digital health systems are facilitating this shift. By providing...
Health care is at a turning point. We are shifting from protocolized medicine to precision medicine, and digital health systems are facilitating this shift. By providing clinicians with detailed information for each patient and analytic support for decision-making at the point of care, digital health technologies are enabling a new era of precision medicine. Genomic data also provide clinicians with information that can improve the accuracy and timeliness of diagnosis, optimize prescribing, and target risk reduction strategies, all of which are key elements for precision medicine. However, genomic data are predominantly seen as diagnostic information and are not routinely integrated into the clinical workflows of electronic medical records. The use of genomic data holds significant potential for precision medicine; however, as genomic data are fundamentally different from the information collected during routine practice, special considerations are needed to use this information in a digital health setting. This paper outlines the potential of genomic data integration with electronic records, and how these data can enable precision medicine.
PubMed: 38935958
DOI: 10.2196/55632 -
Journal of Medical Internet Research Jun 2024Artificial intelligence, particularly chatbot systems, is becoming an instrumental tool in health care, aiding clinical decision-making and patient engagement. (Comparative Study)
Comparative Study
BACKGROUND
Artificial intelligence, particularly chatbot systems, is becoming an instrumental tool in health care, aiding clinical decision-making and patient engagement.
OBJECTIVE
This study aims to analyze the performance of ChatGPT-3.5 and ChatGPT-4 in addressing complex clinical and ethical dilemmas, and to illustrate their potential role in health care decision-making while comparing seniors' and residents' ratings, and specific question types.
METHODS
A total of 4 specialized physicians formulated 176 real-world clinical questions. A total of 8 senior physicians and residents assessed responses from GPT-3.5 and GPT-4 on a 1-5 scale across 5 categories: accuracy, relevance, clarity, utility, and comprehensiveness. Evaluations were conducted within internal medicine, emergency medicine, and ethics. Comparisons were made globally, between seniors and residents, and across classifications.
RESULTS
Both GPT models received high mean scores (4.4, SD 0.8 for GPT-4 and 4.1, SD 1.0 for GPT-3.5). GPT-4 outperformed GPT-3.5 across all rating dimensions, with seniors consistently rating responses higher than residents for both models. Specifically, seniors rated GPT-4 as more beneficial and complete (mean 4.6 vs 4.0 and 4.6 vs 4.1, respectively; P<.001), and GPT-3.5 similarly (mean 4.1 vs 3.7 and 3.9 vs 3.5, respectively; P<.001). Ethical queries received the highest ratings for both models, with mean scores reflecting consistency across accuracy and completeness criteria. Distinctions among question types were significant, particularly for the GPT-4 mean scores in completeness across emergency, internal, and ethical questions (4.2, SD 1.0; 4.3, SD 0.8; and 4.5, SD 0.7, respectively; P<.001), and for GPT-3.5's accuracy, beneficial, and completeness dimensions.
CONCLUSIONS
ChatGPT's potential to assist physicians with medical issues is promising, with prospects to enhance diagnostics, treatments, and ethics. While integration into clinical workflows may be valuable, it must complement, not replace, human expertise. Continued research is essential to ensure safe and effective implementation in clinical environments.
Topics: Humans; Clinical Decision-Making; Artificial Intelligence
PubMed: 38935937
DOI: 10.2196/54571