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1.
Psychol Med ; 54(6): 1074-1083, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38433596

RESUMO

Decision-making capacity (DMC) among psychiatric inpatients is a pivotal clinical concern. A review by Okai et al. (2007) suggested that most psychiatric inpatients have DMC for treatment, and its assessment is reliable. Nevertheless, the high heterogeneity and mixed results from other studies mean there is considerable uncertainty around this topic. This study aimed to update Okai's research by conducting a systematic review with meta-analysis to address heterogeneity. We performed a systematic search across four databases, yielding 5351 results. We extracted data from 20 eligible studies on adult psychiatric inpatients, covering DMC assessments from 2006 to May 2022. A meta-analysis was conducted on 11 papers, and a quality assessment was performed. The study protocol was registered on PROSPERO (ID: CRD42022330074). The proportion of patients with DMC for treatment varied widely based on treatment setting, the specific decision and assessment methods. Reliable capacity assessment was feasible. The Mini-Mental State Examination (MMSE), Global Assessment of Function (GAF), and Brief Psychiatric Rating Scale (BPRS) predicted clinical judgments of capacity. Schizophrenia and bipolar mania were linked to the highest incapacity rates, while depression and anxiety symptoms were associated with better capacity and insight. Unemployment was the only sociodemographic factor correlated with incapacity. Assessing mental capacity is replicable, with most psychiatric inpatients able to make treatment decisions. However, this capacity varies with admission stage, formal status (involuntary or voluntary), and information provided. The severity of psychopathology is linked to mental capacity, though detailed psychopathological data are limited.


Assuntos
Competência Mental , Esquizofrenia , Adulto , Humanos , Competência Mental/psicologia , Pacientes Internados/psicologia , Tomada de Decisões , Incerteza
2.
BMC Palliat Care ; 23(1): 56, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38403633

RESUMO

BACKGROUND: People living with severe mental illness (SMI) face significant health inequalities, including in palliative care. Advance Care Planning (ACP) is widely recommended by palliative care experts and could reduce inequalities. However, implementing ACP with this group is challenging. Electronic Palliative Care Coordination Systems such as Coordinate my Care (CMC) have been introduced to support documentation and sharing of ACP records with relevant healthcare providers. This study explores the use of CMC amongst those with SMI and aims to describe how those with a primary diagnosis of SMI who have used CMC for ACP, and makes recommendations for future research and policy. METHOD: A retrospective observational cohort analysis was completed of CMC records created 01/01/2010-31/09/2021 where the service user had a primary diagnosis of SMI, with no exclusions based on comorbidities. Descriptive statistics were used to report on characteristics including: age, diagnosis, individual prognosis and resuscitation status. Thematic analysis was used to report on the content of patients' statements of preference. RESULTS: 1826 records were identified. Of this sample most (60.1%) had capacity to make treatment decisions, 47.8% were aged under 70, 86.7% were given a prognosis of 'years' and most (63.1%) remained for full cardio-pulmonary resuscitation in the event of cardio-pulmonary arrest. Records with completed statements of preferences (20.3%) contained information about preferences for physical and mental health treatment care as well as information about patient presentation and capacity, although most were brief and lacked expression of patient voice. DISCUSSION: Compared to usual CMC users, the cohort of interest are relatively able, younger people using CMC to make long-term plans for active physical and mental health treatment. ADM is a service user-driven process, and so it was expected that authentic patient voice would be expressed within statements of preference, however this was mostly not achieved. CONCLUSIONS: This digital tool is being used by people with SMI but to plan for more than palliative care. This cohort and supporting professionals have used CMC to plan for longer term physical and mental healthcare. Future research and policy should focus on development of tailored digital tools for people with SMI to plan for palliative, physical and mental healthcare and support expression of patient voice.


Assuntos
Planejamento Antecipado de Cuidados , Transtornos Mentais , Humanos , Idoso , Cuidados Paliativos , Estudos Retrospectivos , Transtornos Mentais/terapia , Atenção à Saúde
3.
Biol Res ; 56(1): 63, 2023 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-38041132

RESUMO

In December 2022 the US Food and Drug Administration (FDA) removed the requirement that drugs in development must undergo animal testing before clinical evaluation, a declaration that now demands the establishment and verification of ex vivo preclinical models that closely represent tumor complexity and that can predict therapeutic response. Fortunately, the emergence of patient-derived organoid (PDOs) culture has enabled the ex vivo mimicking of the pathophysiology of human tumors with the reassembly of tissue-specific features. These features include histopathological variability, molecular expression profiles, genetic and cellular heterogeneity of parental tissue, and furthermore growing evidence suggests the ability to predict patient therapeutic response. Concentrating on the highly lethal and heterogeneous gastrointestinal (GI) tumors, herein we present the state-of-the-art and the current methodology of PDOs. We highlight the potential additions, improvements and testing required to allow the ex vivo of study the tumor microenvironment, as well as offering commentary on the predictive value of clinical response to treatments such as chemotherapy and immunotherapy.


Assuntos
Neoplasias Gastrointestinais , Estados Unidos , Animais , Humanos , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/metabolismo , Organoides/metabolismo , Organoides/patologia , Microambiente Tumoral
4.
Lancet Psychiatry ; 10(11): 887-895, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37714174

RESUMO

Self-binding directives (SBDs) are an ethically controversial type of advance decision making involving advance requests for involuntary treatment. This study systematically reviewed the academic literature on psychiatric SBDs to elucidate reasons for and against their use in psychiatric practice. Full-text articles were thematically analysed within the international, interdisciplinary authorship team to produce a hierarchy of reasons. We found 50 eligible articles. Reasons for SBD use were promoting service user autonomy, promoting wellbeing and reducing harm, improving relationships, justifying coercion, stakeholder support, and reducing coercion. Reasons against SBD use were diminishing service user autonomy, unmanageable implementation problems, difficulties with assessing mental capacity, challenging personal identity, legislative issues, and causing harm. A secondary finding was a clarified concept of capacity-sensitive SBDs. Future pilot implementation projects that operationalise the clarified definition of capacity-sensitive SBDs with safeguards around informed consent, capacity assessment, support for drafting, and independent review are required.

5.
Molecules ; 28(12)2023 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-37375380

RESUMO

The coordination chemistry of scorpionate ligands based on borates containing the 7-azaindole heterocycle is relatively unexplored. Thus, there is a requirement to further understand their coordination chemistry. This article outlines the synthesis and characterization of a family of complexes containing anionic flexible scorpionate ligands of the type [(R)(bis-7-azaindolyl)borohydride]- ([RBai]-), where R = Me, Ph or naphthyl. The three ligands were coordinated to a series of copper(I) complexes containing a phosphine co-ligand to form the complexes, [Cu(MeBai)(PPh3)] (1), [Cu(PhBai)(PPh3)] (2), [Cu(NaphthBai)(PPh3)] (3), [Cu(MeBai)(PCy3)] (4), [Cu(PhBai)(PCy3)] (5) and [Cu(NaphthBai)(PCy3)] (6). Additional copper(II) complexes, namely, [Cu(MeBai)2] (7) and [Cu(PhBai)2] (8), were obtained during attempts to obtain single crystals from complexes 4 and 2, respectively. Complexes 7 and 8 were also prepared independently from CuCl2 and two equivalents of the corresponding Li[RBai] salt alongside an additional complex, namely, [Cu(NaphthBai)2] (9). The copper(I) and copper(II) complexes were characterized using spectroscopic and analytical methods. Furthermore, a crystal structure was obtained for eight of the nine complexes. In all cases, the boron-based ligand was found to bind to the metal centers via a κ3-N,N,H coordination mode.

6.
Med Law Rev ; 31(4): 564-593, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-37295959

RESUMO

For many purposes in England and Wales, the Court of Protection determines whether a person has or lacks capacity to make a decision, by applying the test within the Mental Capacity Act 2005. This test is regularly described as a cognitive test with cognitive processes discussed as internal characteristics. However, it is unclear how the courts have framed interpersonal influence as negatively impacting upon a person's decision-making processes in a capacity assessment context. We reviewed published court judgments in England and Wales in which interpersonal problems were discussed as relevant to capacity. Through content analysis, we developed a typology that highlights five ways the courts considered influence to be problematic to capacity across these cases. Interpersonal influence problems were constructed as (i) P's inability to preserve their free will or independence, (ii) restricting P's perspective, (iii) valuing or dependence on a relationship, (iv) acting on a general suggestibility to influence, or (v) P denying facts about the relationship. These supposed mechanisms of interpersonal influence problems are poorly understood and clearly merit further consideration. Our typology and case discussion are a start towards more detailed practice guidelines, and raise questions as to whether mental capacity and influence should remain legally distinct.


Assuntos
Julgamento , Competência Mental , Humanos , Inglaterra , País de Gales , Tomada de Decisões
7.
Eur Psychiatry ; 66(1): e48, 2023 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-37293987

RESUMO

BACKGROUND: Self-binding directives (SBDs) are psychiatric advance directives that include a clause in which mental health service users consent in advance to involuntary hospital admission and treatment under specified conditions. Medical ethicists and legal scholars identified various potential benefits of SBDs but have also raised ethical concerns. Until recently, little was known about the views of stakeholders on the opportunities and challenges of SBDs. AIMS: This article aims to foster an international exchange on SBDs by comparing recent empirical findings on stakeholders' views on the opportunities and challenges of SBDs from Germany, the Netherlands, and the United Kingdom. METHOD: Comparisons between the empirical findings were drawn using a structured expert consensus process. RESULTS: Findings converged on many points. Perceived opportunities of SBDs include promotion of autonomy, avoidance of personally defined harms, early intervention, reduction of admission duration, improvement of the therapeutic relationship, involvement of persons of trust, avoidance of involuntary hospital admission, addressing trauma, destigmatization of involuntary treatment, increase of professionals' confidence, and relief for proxy decision-makers. Perceived challenges include lack of awareness and knowledge, lack of support, undue influence, inaccessibility during crisis, lack of cross-agency coordination, problems of interpretation, difficulties in capacity assessment, restricted therapeutic flexibility, scarce resources, disappointment due to noncompliance, and outdated content. Stakeholders tended to focus on practical challenges and did not often raise fundamental ethical concerns. CONCLUSIONS: Stakeholders tend to see the implementation of SBDs as ethically desirable, provided that the associated challenges are addressed.


Assuntos
Diretivas Antecipadas , Serviços de Saúde Mental , Humanos , Europa (Continente) , Procurador , Pesquisa Empírica
9.
BMC Psychiatry ; 23(1): 344, 2023 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-37198589

RESUMO

BACKGROUND: The UK government committed to legislating for Advance Choice Documents/Advance Statements (ACD/AS) following their recommendation by the Independent Review of the MHA (2018). ACDs/AS are yet to be implemented in routine practice despite evidence and high demand; they are associated with improved therapeutic relationships and a reduction (25%, RR 0.75, CI 0.61-0.93) in compulsory psychiatric admission. Barriers to their implementation are well documented, ranging from low knowledge levels to logistical challenges in accessing the content during episodes of acute care. In the UK this is an issue for Black people, who experience detention rates disproportionately (over three times) higher than those of White British people and have poorer care experiences and outcomes. ACDs/AS allow for Black people to have their concerns heard by mental health professionals in a care system where they often feel their views are ignored. AdStAC aims to improve Black service users' experiences in mental health services in South London by co-producing and testing an ACD/AS implementation resource with Black service users, mental health professionals and carers/supporters of Black service users. METHODS/DESIGN: The study will take place in South London, England over three phases: 1) formative work through stakeholder workshops; 2) co-production of resources through a consensus development exercise and working groups; and 3) testing of the resources using quality improvement (QI) methods. A lived experience advisory group, staff advisory group and project steering committee will support the study throughout. The implementation resources will comprise: advance choice document/advance statement (ACD/AS) documentation, stakeholder trainings, a manual for mental health professionals to facilitate the processes of creating and revising advance statements, and informatics development. DISCUSSION: The implementation resources will help increase the likelihood of the new mental health legislation in England being implemented effectively; through aligning evidence-based medicine, policy and law to effectively provide positive clinical, social and financial outcomes for Black people, the National Health Service (NHS) and wider society. This study will likely benefit a wider group of people with severe mental illness, as when marginalised groups who are least engaged, can be supported with these strategies, then the strategies are likely to work for others.


Assuntos
Transtornos Mentais , Serviços de Saúde Mental , Humanos , Medicina Estatal , População do Caribe , Transtornos Mentais/terapia , Transtornos Mentais/psicologia , População Negra
10.
Inorg Chem ; 62(17): 6704-6710, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37058454

RESUMO

Reaction of a new ligand 6-DiPPon (6-diisopropylphosphino-2-pyridone) with 0.5 equiv of [RuCl2(p-cymene)]2 resulted in the formation of a mixture of [RuCl2(p-cymene)(κ1-P-6-DiPPon)]2 (1) and [RuCl(p-cymene)(κ2-P,N-6-DiPPin)]Cl ([2]Cl) (where 6-DiPPin = 6-diisopropylphosphino-2-hydroxypyridine). The ratio between the two products can be controlled by the nature of the solvent. The similar reaction between 6-DiPPon and [RuCl2(p-cymene)]2 in the presence of AgOTf and Na[BArF24] (where BArF24 = [{3,5-(CF3)2C6H3}4B]-) resulted in the formation of the complexes [RuCl(p-cymene)(κ2-P,N-6-DiPPin)]OTf, ([2]OTf) and [RuCl(p-cymene)(κ2-P,N-6-DiPPin)]BArF24 ([2]BArF24), respectively. Reactions between complex [2]Cl, [2]OTf, or [2]BArF24 and a base (either DBU or NaOMe) resulted in the deprotonation of the hydroxyl functional group to form a novel neutral orange-colored dearomatized complex, 3. The identity of complex 3 was confirmed as [RuCl(p-cymene)(κ2-P,N-6-DiPPon*)], where 6-DiPPon* is the anionic species (6-diisopropylphosphino-2-oxo-pyridinide), which contains the deprotonated moiety. The new 6-DiPPon ligand and its corresponding air stable half-sandwich derivative ruthenium complexes 1, [2]OTf, [2]BArF24, and 3 were all isolated in good yields and fully characterized by spectroscopic and analytical methods. The interconversions between the neutral and anionic forms of the ligands 6-DiPPon, 6-DiPPin, and 6-DiPPon* offer the potential for novel secondary sphere interactions and proton shuttling reactivity. The consequences for this have been explored in the activation of H2 and the subsequent catalytic hydrogenations of CO2 into formate salts in the presence of a base.

11.
Psychol Med ; 53(5): 1700-1707, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36878884

RESUMO

The practice of formulation has been both championed and severely criticised within clinical psychiatry and interest in formulation within the teaching of clinical psychiatry is at a low ebb. This article traces the history of the biopsychosocial model, the concept of diagnostic hierarchy and the role of 'verstehen' (or intersubjective meaning grasping) in the clinical assessment. All three of these concepts are considered relevant to the practice of formulation. Responding to challenges aimed at these concepts, it argues that formulation in psychiatry needs resuscitating and rethinking and provides some recommendations for a practice of formulation fit for the 21st century.


Assuntos
Psiquiatria
12.
Cells ; 12(3)2023 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-36766848

RESUMO

Glioblastoma (GBM) is the most common and aggressive type of brain tumor due to its elevated recurrence following treatments. This is mainly mediated by a subpopulation of cells with stemness traits termed glioblastoma stem-like cells (GSCs), which are extremely resistant to anti-neoplastic drugs. Thus, an advancement in the understanding of the molecular processes underlying GSC occurrence should contribute significantly towards progress in reducing aggressiveness. High levels of endothelin-converting enzyme-1 (ECE1), key for endothelin-1 (ET-1) peptide activation, have been linked to the malignant progression of GBM. There are four known isoforms of ECE1 that activate ET-1, which only differ in their cytoplasmic N-terminal sequences. Isoform ECE1c is phosphorylated at Ser-18 and Ser-20 by protein kinase CK2, which increases its stability and hence promotes aggressiveness traits in colon cancer cells. In order to study whether ECE1c exerts a malignant effect in GBM, we designed an ECE1c mutant by switching a putative ubiquitination lysine proximal to the phospho-serines Lys-6-to-Arg (i.e., K6R). This ECE1cK6R mutant was stably expressed in U87MG, T98G, and U251 GBM cells, and their behavior was compared to either mock or wild-type ECE1c-expressing clone cells. ECE1cK6R behaved as a highly stable protein in all cell lines, and its expression promoted self-renewal and the enrichment of a stem-like population characterized by enhanced neurospheroid formation, as well as increased expression of stem-like surface markers. These ECE1cK6R-derived GSC-like cells also displayed enhanced resistance to the GBM-related chemotherapy drugs temozolomide and gemcitabine and increased expression of the ABCG2 efflux pump. In addition, ECE1cK6R cells displayed enhanced metastasis-associated traits, such as the modulation of adhesion and the enhancement of cell migration and invasion. In conclusion, the acquisition of a GSC-like phenotype, together with heightened chemoresistance and invasiveness traits, allows us to suggest phospho-ECE1c as a novel marker for poor prognosis as well as a potential therapeutic target for GBM.


Assuntos
Glioblastoma , Humanos , Glioblastoma/metabolismo , Enzimas Conversoras de Endotelina/genética , Enzimas Conversoras de Endotelina/metabolismo , Linhagem Celular Tumoral , Células-Tronco Neoplásicas/patologia , Fenótipo
13.
Med Law Rev ; 31(3): 340-357, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36637251

RESUMO

Challenges to the legitimacy of mental capacity over the past 10 years have been spearheaded by the Committee on the Rights of Persons with Disabilities, the treaty body for the UN Convention on the Rights of Persons with Disabilities (CRPD). This challenge has been asserted to have produced a 'paradigm shift'. In this article, we examine why that interpretation has had such limited traction in the legal policy arena, and whether it should have traction. We also analyse whether the Committee has subtly but importantly shifted its position. We then develop an argument that the true goal, compatible with the CRPD, is the satisfactory determination of whether a person has or lacks mental capacity to make or take a relevant decision. Our article contextualises multi-disciplinary, research-informed guidelines designed as a contribution to satisfactory determination. While our article is based upon the position in England and Wales, we suggest that our conclusions are of wider application.


Assuntos
Pessoas com Deficiência , Transtornos Mentais , Humanos , Direitos Humanos , Nações Unidas , Cooperação Internacional , Inglaterra
14.
Wellcome Open Res ; 7: 182, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36081756

RESUMO

Background Advance Decision Making (ADM) is strongly supported by stakeholders but implementation remains challenging. In England and Wales, implementation strategies are urgently required to prepare for the introduction of mental health 'Advance Choice Documents' (ACDs) as part of Mental Health Act reforms. We report on a pilot project which aimed to co-produce and evaluate implementation strategies for ACDs with those who experience fluctuating mental capacity in the context of bipolar. Methods A co-produced prototype ACD template was piloted in 'Plan, Do, Study Act' (PDSA) cycles. Implementation strategies were co-produced with participants and mapped onto the Expert Recommendations for Implementing Change (ERIC) framework. Strategies were evaluated during thematically analysed qualitative interviews. Results We piloted the template with 17 service users during 5 successive PDSA cycles and conducted 75 in depth interviews with stakeholders. Key strategies identified as accessible, appropriate and feasible were: interactive assistance from an independent 'supporter', a structured template and active offers of involvement to service users and informal carers. Conclusions Mental health professionals and organisations must prepare for increased expectations around mental health ADM. We recommend further pilot projects and the establishment of 'ACD workshops'. Resource is essential to fund independent 'supporters', training, network building and embedding ADM in clinical pathways.

15.
Dalton Trans ; 51(31): 11582-11611, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35839074

RESUMO

A portfolio of value-added chemicals, fuels and building block compounds can be envisioned from CO2 on an industrial scale. The high kinetic and thermodynamic stabilities of CO2, however, present a significant barrier to its utilisation as a C1 source. In this context, metal-ligand cooperation methodologies have emerged as one of the most dominant strategies for the transformation of the CO2 molecule over the last decade or so. This review focuses on the advancements in CO2 transformation using these cooperative methodologies. Different and well-studied ligand cooperation methodologies, such as dearomatisation-aromatisation type cooperation, bimetallic cooperation (M⋯M'; M' = main group or transition metal) and other related strategies are also discussed. Furthermore, the cooperative bond activations are subdivided based on the number of atoms connecting the reactive centre in the ligand framework (spacer/linker length) and the transition metal. Several similarities across these seemingly distinct cooperative methodologies are emphasised. Finally, this review brings out the challenges ahead in developing catalytic systems from these CO2 transformations.


Assuntos
Dióxido de Carbono , Elementos de Transição , Dióxido de Carbono/química , Catálise , Ligantes , Metais/química
16.
Front Psychiatry ; 13: 946234, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35898632

RESUMO

Background: Assessment of capacity for treatment and discharge decisions is common in the general hospital. Liaison psychiatrists are often asked to support the treating medical or surgical team in difficult capacity assessments. However, empirical research on identification and resolution of difficult capacity cases is limited. Some studies have identified certain patient, decisional, and interpersonal factors which cause difficulty, but no study has explored how these issues are resolved in practice. Our study therefore aimed to describe how experienced liaison psychiatrists identify and resolve difficult capacity cases in a general hospital setting. Methods: We carried out semi-structured interviews with 26 liaison psychiatrists from England, Scotland, and New Zealand, on their most difficult capacity cases. Thematic analysis was used to examine types of difficulty and how these were resolved in practice. Summaries were prepared and example quotes extracted to illustrate phenomena described. Results: We identified four types of difficulty in capacity assessment, spanning both clinical and ethical domains: 1) Difficulty determining whether the decision is the patient's own or driven by illness, 2) Difficulty in applying ethical principles, 3) Difficulty in avoiding personal bias, and 4) Procedural difficulties. The liaison psychiatrists presented as self-reflective and aware of challenges and pitfalls in hard cases. We summarized their creative strategies to resolve difficulty in assessment. Conclusion: Practitioners approaching difficult capacity cases require both clinical skills, e.g., to uncover subtle illness impairing decision-making and to consider interpersonal dynamics, and ethical skills, e.g., to negotiate the role of values and risks in capacity assessment. Education and training programmes should incorporate both aspects and could include the resolution strategies identified in our study. Practitioners, supported by health and social care systems, should work to develop self-aware and reflective capacity assessment practice.

17.
J Surg Case Rep ; 2022(4): rjac160, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35481249

RESUMO

Primary tumors of the omentum, let alone omental lipomas, are rare causes of a large intra-abdominal mass. We report a case of an adult male presenting with an intra-abdominal mass, representative of a giant omental lipoma radiologically, confirmed on histopathology after complete resection at laparotomy. The case highlights the preoperative workup of a suspected omental lipoma, including the utility of various radiological modalities in differentiating from malignant pathologies, and anatomical characterization of the lesion for surgical planning.

18.
Int J Mol Sci ; 24(1)2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36613445

RESUMO

Recently, the combination of chemotherapy plus nivolumab (chemo-immunotherapy) has become the standard of care for advanced-stage gastric cancer (GC) patients. However, despite its efficacy, up to 40% of patients do not respond to these treatments. Our study sought to identify variations in gene expression associated with primary resistance to chemo-immunotherapy. Diagnostic endoscopic biopsies were retrospectively obtained from advanced GC patients previously categorized as responders (R) or non-responders (NR). Thirty-four tumor biopsies (R: n = 16, NR: n = 18) were analyzed by 3' massive analysis of cDNA ends (3'MACE). We found >30 differentially expressed genes between R and NRs. Subsequent pathway enrichment analyses demonstrated that angiogenesis and the Wnt-ß-catenin signaling pathway were enriched in NRs. Concomitantly, we performed next generation sequencing (NGS) analyses in a subset of four NR patients that confirmed alterations in genes that belonged to the Wnt/ß-catenin and the phosphoinositide 3-kinase (PI3K) pathways. We speculate that angiogenesis, the Wnt, and the PI3K pathways might offer actionable targets. We also discuss therapeutic alternatives for chemo-immunotherapy-resistant advanced-stage GC patients.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , beta Catenina/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Estudos Retrospectivos , Via de Sinalização Wnt/genética , Imunoterapia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
19.
J Med Ethics ; 48(11): 838-844, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-34341150

RESUMO

Most jurisdictions require that a mental capacity assessment be conducted using a functional model whose definition includes several abilities. In England and Wales and in increasing number of countries, the law requires a person be able to understand, to retain, to use or weigh relevant information and to communicate one's decision. But interpreting and applying broad and vague criteria, such as the ability 'to use or weigh' to a diverse range of presentations is challenging. By examining actual court judgements of capacity, we previously developed a descriptive typology of justifications (rationales) used in the application of the Mental Capacity Act (MCA) criteria. We here critically optimise this typology by showing how clear definitions-and thus boundaries-between the criteria can be achieved if the 'understanding' criterion is used narrowly and the multiple rationales that fall under the ability to 'use or weigh' are specifically enumerated in practice. Such a typology-aided practice, in theory, could make functional capacity assessments more transparent, accountable, reliable and valid. It may also help to create targeted supports for decision making by the vulnerable. We also discuss how the typology could evolve legally and scientifically, and how it lays the groundwork for clinical research on the abilities enumerated by the MCA.


Assuntos
Tomada de Decisões , Competência Mental , Humanos , Inglaterra , País de Gales
20.
Int J Soc Psychiatry ; 68(7): 1494-1506, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-34348507

RESUMO

BACKGROUND: Insight into illness is often used in clinical and legal contexts, for example, as evidence of decision-making capacity. However, it is unclear whether this disadvantages certain groups protected under equality legislation. To our knowledge, this question has yet to be addressed systematically. Therefore, the present study reviews empirical studies that look at the relationship between insight and sociodemographic variables. METHODS: A systematic search of six bibliographic databases (CENTRAL, CINAHL, Cochrane Library of Systematic Reviews, EMBASE, MEDLINE and PsycINFO) was conducted, which yielded 6,192 results. Study characteristics and outcomes (associations between insight and socio-demographic variables) were then extracted from 207 eligible studies. This included protected characteristics under the Equality Act (2010): age, sex, ethnicity, marital status and religion. Weighted confidence estimates were calculated and relevant moderators included in a random effects meta-analysis. A study protocol was registered prospectively on PROSPERO, ID: CRD42019120117. RESULTS: Insight was not strongly associated with any sociodemographic variable. Better insight was weakly but significantly associated with white ethnicity, being employed, younger age and more years of education. The age associations were mostly explained by relevant moderating variables. For people with schizophrenia, the associations between sociodemographic variables and insight were comparable to associations with decision making capacity. CONCLUSIONS: Our results suggest that insight is not strongly associated with any sociodemographic variables. Further research is needed to clarify potential associations, particularly with non-white ethnicity and proxies for social support.


Assuntos
Esquizofrenia , Apoio Social , Etnicidade , Humanos , Religião
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