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Journal of Neurological Surgery. Part... Jul 2024End-of-life (EoL) decisions are routine in neurosurgical care due to frequent devastating and life-threatening diagnoses. Advance directives, discussions with...
BACKGROUND
End-of-life (EoL) decisions are routine in neurosurgical care due to frequent devastating and life-threatening diagnoses. Advance directives, discussions with patients' relatives, and evaluation of the alleged will of the patient play an increasing important role in clinical decision-making. Institutional standards, ethical values, different ethnical backgrounds, and individual physician's experiences influence clinical judgments and decisions. We hypothesize that the implementation of palliative care in neurosurgical wards needs optimization. The aim of this study is to identify possible sources of error and to share our experiences.
METHODS
This is a retrospective observational analysis. One hundred and sixty-eight patients who died on a regular neurosurgical ward between 2014 and 2019 were included. Medical reports were analyzed in detail. A differentiation between consistent and nonconsistent palliation was made, with consistent palliative care consisting of discontinuation of medication that was no longer indicated, administration of medication for symptom control, and consequent discontinuation of nutrition and fluid substitution that went beyond satisfying hunger or thirst.
RESULTS
EoL decisions were made in 127 (84.1%) of all 168 cases; 100 patients were included in our analysis. Of these patients, only 24 had an advance directive, and the relatives were included in the communication about the therapy goals in 71 cases. Discontinuation of medication that is not for symptom control was performed in 63 patients, food withdrawal in 66 patients, and fluid substitution that went beyond the quenching of thirst was withdrawn in 27 patients. Thus, consistent palliative care was realized in 25% of all patients. The mean duration from the EoL decision until death was 2.1 days (range: 0-20 days). If a consistent palliative care was carried out, patients survived significantly shorter (nonconsistent palliative care: 2.4 days; range: 0-10 days vs. consistent palliative care: 1.2 days; range: 0-4 days; = 0.008).
CONCLUSIONS
The therapy goal should be thoroughly considered and determined at an early stage. If an EoL decision is reached, consistent palliative care should be carried out in order to limit suffering of moribund patients.
PubMed: 38959942
DOI: 10.1055/s-0043-1771278 -
EBioMedicine Jul 2024The clinical heterogeneity of myasthenia gravis (MG), an autoimmune disease defined by antibodies (Ab) directed against the postsynaptic membrane, constitutes a...
BACKGROUND
The clinical heterogeneity of myasthenia gravis (MG), an autoimmune disease defined by antibodies (Ab) directed against the postsynaptic membrane, constitutes a challenge for patient stratification and treatment decision making. Novel strategies are needed to classify patients based on their biological phenotypes aiming to improve patient selection and treatment outcomes.
METHODS
For this purpose, we assessed the serum proteome of a cohort of 140 patients with anti-acetylcholine receptor-Ab-positive MG and utilised consensus clustering as an unsupervised tool to assign patients to biological profiles. For in-depth analysis, we used immunogenomic sequencing to study the B cell repertoire of a subgroup of patients and an in vitro assay using primary human muscle cells to interrogate serum-induced complement formation.
FINDINGS
This strategy identified four distinct patient phenotypes based on their proteomic patterns in their serum. Notably, one patient phenotype, here named PS3, was characterised by high disease severity and complement activation as defining features. Assessing a subgroup of patients, hyperexpanded antibody clones were present in the B cell repertoire of the PS3 group and effectively activated complement as compared to other patients. In line with their disease phenotype, PS3 patients were more likely to benefit from complement-inhibiting therapies. These findings were validated in a prospective cohort of 18 patients using a cell-based assay.
INTERPRETATION
Collectively, this study suggests proteomics-based clustering as a gateway to assign patients to a biological signature likely to benefit from complement inhibition and provides a stratification strategy for clinical practice.
FUNDING
CN and CBS were supported by the Forschungskommission of the Medical Faculty of the Heinrich Heine University Düsseldorf. CN was supported by the Else Kröner-Fresenius-Stiftung (EKEA.38). CBS was supported by the Deutsche Forschungsgemeinschaft (DFG-German Research Foundation) with a Walter Benjamin fellowship (project 539363086). The project was supported by the Ministry of Culture and Science of North Rhine-Westphalia (MODS, "Profilbildung 2020" [grant no. PROFILNRW-2020-107-A]).
PubMed: 38959848
DOI: 10.1016/j.ebiom.2024.105231 -
European Journal of Surgical Oncology :... Jun 2024Preoperative geriatric-specific variables (GSV) influence short-term morbidity in surgical patients, but their impact on long-term survival in elderly patients with...
BACKGROUND
Preoperative geriatric-specific variables (GSV) influence short-term morbidity in surgical patients, but their impact on long-term survival in elderly patients with cancer remains undefined.
STUDY DESIGN
This observational cohort study included patients ≥65 years who underwent hepatopancreatobiliary or colorectal operations for malignancy between 2014 and 2020. Individual patient data included merged ACS NSQIP data, Procedure Targeted, and Geriatric Surgery Research variables. Patients were stratified by age: 65-74, 75-84, and ≥85 and presence of these GSVs: mobility aid, preoperative falls, surrogate signed consent, and living alone. Bivariable and multivariable analyses were used to evaluate 1-year mortality and postoperative discharge to facility.
RESULTS
577 patients were included: 62.6 % were 65-74 years old, 31.7 % 75-84, and 5.7 % ≥ 85. 96 patients were discharged to a facility with frequency increasing with age group (11.4 % vs 22.4 % vs 42.4 %, respectively, p < 0.001). 73 patients (12.7 %) died during 1-year follow-up, 32.9 % from cancer recurrence. One-year mortality was associated with undergoing hepatopancreatobiliary operations (p = 0.017), discharge to a facility (p = 0.047), and a surrogate signing consent (p = 0.035). Increasing age (p < 0.001), hepatopancreatobiliary resection (p = 0.002), living home alone (p < 0.001), and mobility aid use (p < 0.001) were associated with discharge to a facility.
CONCLUSION
Geriatric-specific variables, living alone and use of a mobility aid, were associated with discharge to a facility. A surrogate signing consent and discharge to a facility were associated with 1-year mortality. These findings underscore the importance of preoperative patient selection and optimization, efficacious discharge planning, and informed decision-making in the care of elderly cancer patients.
PubMed: 38959846
DOI: 10.1016/j.ejso.2024.108509 -
Current Opinion in Psychology Jun 2024Machine Learning (ML) affords researchers tools to advance beyond research methods commonly employed in psychology, business, and public policy studies of federal... (Review)
Review
Machine Learning (ML) affords researchers tools to advance beyond research methods commonly employed in psychology, business, and public policy studies of federal nutrition programs and participant food decision-making. It is a sub domain of AI that is applied for feature extraction - a crucial step in decision making. These features are used in context-specific automated decisions resulting in predictive AI models. Whereas many prior studies rely on retrospective, static, "one-shot" decision-making in controlled laboratory environments, ML allows researchers to refine predictions about participation and food behaviors using large-scale datasets. We propose a case study using ML to predict an aspect of participation in a large, publicly funded nutrition education program (The Expanded Food and Nutrition Education Program). Participation has important downstream implications for diet quality, food security, and other important nutrition related decisions. We then suggest a process for validating the ML insights using qualitative research and survey data.
PubMed: 38959778
DOI: 10.1016/j.copsyc.2024.101830 -
European Journal of Medicinal Chemistry Jun 2024Agents that cause apoptotic cell death by interfering with tubulin dynamics, such as vinblastine and paclitaxel, are an important class of chemotherapeutics....
Agents that cause apoptotic cell death by interfering with tubulin dynamics, such as vinblastine and paclitaxel, are an important class of chemotherapeutics. Unfortunately, these compounds are substrates for multidrug resistance (MDR) pumps, allowing cancer cells to gain resistance to these chemotherapeutics. The indolesulfonamide family of tubulin inhibitors are not excluded by MDR pumps and have a promising activity profile, although their high lipophilicity is a pharmacokinetic limitation for their clinical use. Here we present a new family of N-indolyl-3,4,5-trimethoxybenzenesulfonamide derivatives with modifications on the indole system at positions 1 and 3 and on the sulfonamide nitrogen. We synthesized and screened against HeLa cells 34 novel indolic benzenesulfonamides. The most potent derivatives (1.7-109 nM) were tested against a broad panel of cancer cell lines, which revealed that substituted benzenesulfonamides analogs had highest potency. Importantly, these compounds were only moderately toxic to non-tumorigenic cells, suggesting the presence of a therapeutic index. Consistent with known clinical anti-tubulin agents, these compounds arrested the cell cycle at G/M phase. Mechanistically, they induced apoptosis via caspase 3/7 activation, which occurred during M arrest. The substituents on the sulfonamide nitrogen appeared to determine different mechanistic results and cell fates. These results suggest that the compounds act differently depending on the bridge substituents, thus making them very interesting as mechanistic probes as well as potential drugs for further development.
PubMed: 38959729
DOI: 10.1016/j.ejmech.2024.116617 -
European Journal of Radiology Jun 2024To assess the perceptions and attitudes of radiologists toward the adoption of artificial intelligence (AI) in clinical practice.
PURPOSE
To assess the perceptions and attitudes of radiologists toward the adoption of artificial intelligence (AI) in clinical practice.
METHODS
A survey was conducted among members of the SIRM Lombardy. Radiologists' attitudes were assessed comprehensively, covering satisfaction with AI-based tools, propensity for innovation, and optimism for the future. The questionnaire consisted of two sections: the first gathered demographic and professional information using categorical responses, while the second evaluated radiologists' attitudes toward AI through Likert-type responses ranging from 1 to 5 (with 1 representing extremely negative attitudes, 3 indicating a neutral stance, and 5 reflecting extremely positive attitudes). Questionnaire refinement involved an iterative process with expert panels and a pilot phase to enhance consistency and eliminate redundancy. Exploratory data analysis employed descriptive statistics and visual assessment of Likert plots, supported by non-parametric tests for subgroup comparisons for a thorough analysis of specific emerging patterns.
RESULTS
The survey yielded 232 valid responses. The findings reveal a generally optimistic outlook on AI adoption, especially among young radiologist (<30) and seasoned professionals (>60, p<0.01). However, while 36.2 % (84 out 232) of subjects reported daily use of AI-based tools, only a third considered their contribution decisive (30 %, 25 out of 84). AI literacy varied, with a notable proportion feeling inadequately informed (36 %, 84 out of 232), particularly among younger radiologists (46 %, p < 0.01). Positive attitudes towards the potential of AI to improve detection, characterization of anomalies and reduce workload (positive answers > 80 %) and were consistent across subgroups. Radiologists' opinions were more skeptical about the role of AI in enhancing decision-making processes, including the choice of further investigation, and in personalized medicine in general. Overall, respondents recognized AI's significant impact on the radiology profession, viewing it as an opportunity (61 %, 141 out of 232) rather than a threat (18 %, 42 out of 232), with a majority expressing belief in AI's relevance to future radiologists' career choices (60 %, 139 out of 232). However, there were some concerns, particularly among breast radiologists (20 of 232 responders), regarding the potential impact of AI on the profession. Eighty-four percent of the respondents consider the final assessment by the radiologist still to be essential.
CONCLUSION
Our results indicate an overall positive attitude towards the adoption of AI in radiology, though this is moderated by concerns regarding training and practical efficacy. Addressing AI literacy gaps, especially among younger radiologists, is essential. Furthermore, proactively adapting to technological advancements is crucial to fully leverage AI's potential benefits. Despite the generally positive outlook among radiologists, there remains significant work to be done to enhance the integration and widespread use of AI tools in clinical practice.
PubMed: 38959557
DOI: 10.1016/j.ejrad.2024.111590 -
Journal of Evaluation in Clinical... Jul 2024This is a protocol of a scoping review that will aim to synthesise methodological evidence on formulating plain language versions of recommendations from guidelines both... (Review)
Review
AIMS AND OBJECTIVES
This is a protocol of a scoping review that will aim to synthesise methodological evidence on formulating plain language versions of recommendations from guidelines both for clinical practice and for public health.
METHOD
We will conduct a search in MEDLINE (Ovid), Embase (Ovid) databases, and webpages of guidelines developers with no language and date limitations. The title/abstract and full-text screening will be performed by two reviewers independently. The team of reviewers will extract data on methods used for developing plain language versions of recommendations in a standardised manner. The data analysis and synthesis will be presented narratively in tabular form.
RESULTS AND CONCLUSION
We will conduct a scoping review based on this protocol.
PubMed: 38959391
DOI: 10.1111/jep.14075 -
Journal of Evaluation in Clinical... Jul 2024Reimbursement process of oncology drugs in Europe occurs within a complex decision-making process that varies between Member States. Distinctions between the States... (Review)
Review
RATIONALE
Reimbursement process of oncology drugs in Europe occurs within a complex decision-making process that varies between Member States. Distinctions between the States trigger societal debates since it is necessary to balance access to medicines and health systems sustainability.
AIMS AND OBJECTIVES
We aimed to review the evidence concerning factors associated with the reimbursement decision or Health Technology Agency recommendation of oncology drugs in Europe.
METHODS
A systematic literature search was performed in two databases from inception to august 2023. Screening and data extraction were performed by pairs.
RESULTS
Thirteen articles were included and encompassed data from 11 nations. Seven articles showed that cost-effective (C-E) drugs and lower Incremental Cost-Effectiveness Ratios (ICERs) had higher likelihood of reimbursement. Disease severity might influence the reimbursement decision with financial agreements. Improvement in clinical outcomes, substantial clinical benefit (p < 0.01) or overall survival gains (p < 0.05) were positively associated. Orphan drug designation impact varies between countries but positive decisions are usually achieved under specific conditions. Clinical and C-E uncertainty frequently led to reimbursement with financial agreements or outcomes-based conditions. Sociodemographic factors as: social health insurance system, higher Gross Domestic Product and larger elderly population were positively associated with reimbursement (p < 0.01).
CONCLUSION
There is a need for further research into key determinants of reimbursement decisions in Europe and the development of drug access models that can effectively address and overcome costs and effectiveness uncertainties.
PubMed: 38959379
DOI: 10.1111/jep.14080 -
Journal of Evaluation in Clinical... Jul 2024Addressing Diversity, Equity and Inclusion in health care is a multidimensional challenge. From a US perspective, the third-party payment system has disempowered and...
Addressing Diversity, Equity and Inclusion in health care is a multidimensional challenge. From a US perspective, the third-party payment system has disempowered and depersonalized health-care delivery. The net result is wasteful and inefficient use of human and financial resources, burnout among providers, as well as care inequities. Financial integration at the point of patient care is essential to aligning the needs of patients with advances in medical technology. Complexity theory offers valuable insights into the roles of government, intermediaries and patients. The government must focus on equity as a rule compiler and referee of the system. Patient and providers who are actively engaged in shared decision-making will naturally address the diverse needs of multitudinous communities. Intermediaries address inclusion by connecting resources with the point of care. In a dynamic, emerging health-care system that serves diverse communities, patient and community-based financing, vouchers and defined contributions are necessary first steps in addressing cultural diversity, inclusion and equity.
PubMed: 38959378
DOI: 10.1111/jep.14073 -
Pediatric Critical Care Medicine : a... Jul 2024To derive systematic-review informed, modified Delphi consensus regarding the management of bleeding and thrombotic complications during pediatric extracorporeal...
Management of Bleeding and Thrombotic Complications During Pediatric Extracorporeal Membrane Oxygenation: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.
OBJECTIVES
To derive systematic-review informed, modified Delphi consensus regarding the management of bleeding and thrombotic complications during pediatric extracorporeal membrane oxygenation (ECMO) for the Pediatric ECMO Anticoagulation CollaborativE Consensus Conference.
DATA SOURCES
A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021.
STUDY SELECTION
The management of bleeding and thrombotic complications of ECMO.
DATA EXTRACTION
Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Twelve references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form.
DATA SYNTHESIS
Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements for the management of bleeding and thrombotic complications in pediatric ECMO patients. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. Two good practice statements, 5 weak recommendations, and 18 consensus statements are presented.
CONCLUSIONS
Although bleeding and thrombotic complications during pediatric ECMO remain common, limited definitive data exist to support an evidence-based approach to treating these complications. Research is needed to improve hemostatic management of children supported with ECMO.
Topics: Extracorporeal Membrane Oxygenation; Humans; Thrombosis; Hemorrhage; Child; Delphi Technique; Anticoagulants; Consensus
PubMed: 38959361
DOI: 10.1097/PCC.0000000000003489