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1.
Br J Psychiatry ; 224(1): 3-5, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37850424

RESUMO

High mortality rates and poor outcomes from eating disorders, especially anorexia nervosa, are largely preventable and require urgent action. A national strategy to address this should include prevention; early detection; timely access to integrated physical and psychological treatments; safe management of emergencies; suicide prevention; and investment in training, services and research.


Assuntos
Anorexia Nervosa , Bulimia Nervosa , Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Anorexia Nervosa/psicologia , Prevenção do Suicídio , Bulimia Nervosa/psicologia
2.
BMC Psychiatry ; 23(1): 486, 2023 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-37420228

RESUMO

BACKGROUND: People with mental health difficulties often experience social isolation. The importance of interventions to enhance social networks and reduce this isolation is increasingly being recognised. However, the literature has not yet been systematically reviewed with regards to how these are best used. This narrative synthesis aimed to investigate the role of social network interventions for people with mental health difficulties and identify barriers and facilitators to effective delivery. This was undertaken with a view to understanding how social network interventions might work best in the mental health field. METHODS: Systematic searches using combinations of synonyms for mental health difficulties and social network interventions were undertaken across 7 databases (MEDLINE, Embase, PsycINFO, CINAHL, Cochrane Library, Web of Science) and 2 grey literature databases (EThoS and OpenGrey) from their inception to October 2021. We included studies reporting primary qualitative and quantitative data from all study types relating to the use of social network interventions for people with mental health difficulties. The quality of included studies was assessed using the Mixed Methods Appraisal Tool. Data were extracted and synthesised narratively. RESULTS: The review included 54 studies, reporting data from 6,249 participants. Social network interventions were generally beneficial for people with mental health difficulties but heterogeneity in intervention type, implementation and evaluation made it difficult to draw definitive conclusions. Interventions worked best when they (1) were personalised to individual needs, interests and health, (2) were delivered outside formal health services and (3) provided the opportunity to engage in authentic valued activities. Several barriers to access were identified which, without careful consideration could exacerbate existing health inequalities. Further research is required to fully understand condition-specific barriers which may limit access to, and efficacy of, interventions. CONCLUSIONS: Strategies for improving social networks for people with mental health difficulties should focus on supporting engagement with personalised and supported social activities outside of formal mental health services. To optimise access and uptake, accessibility barriers should be carefully considered within implementation contexts and equality, diversity and inclusion should be prioritised in intervention design, delivery and evaluation and in future research.


Assuntos
Saúde Mental , Rede Social , Adulto , Humanos , Isolamento Social
3.
Soc Psychiatry Psychiatr Epidemiol ; 57(5): 907-925, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35138427

RESUMO

BACKGROUND: Social connections have been linked to the genesis and amelioration of mental health problems and thus have potential therapeutic value. PURPOSE: To identify the current evidence base, assess risk of bias and synthesise findings on the effectiveness of social network interventions for people with mental health problems. METHODS: Electronic databases (MEDLINE, Embase, PsycINFO, CINAHL, Cochrane Library, Web of Science, Scopus) and grey literature databases were systematically searched from inception to October 2021 using free text syntax combining synonyms for 'mental health problems' and 'social network interventions'. Articles were eligible for inclusion if they reported data from randomised controlled trials on the effectiveness of interventions designed to improve social networks for adults (18+) with mental health problems. Papers were independently reviewed for inclusion with conflicts resolved through consensus. Included papers were quality assessed and data extracted and synthesized narratively. Risk of bias was assessed using the Cochrane Risk of Bias Tool. RESULTS: Nine studies randomising 2226 participants were included. Four focused on those with a diagnosis of schizophrenia or psychosis, one on major depressive disorder and four included all types of mental health diagnoses. The current evidence base is of unclear quality. However, interventions which focused on supporting social activities appear to hold the most promise for enhancing social networks. Data on cost-effectiveness and research acceptability were limited, but suggest the potential economic feasibility of and acceptability for evaluating these interventions. CONCLUSION: There is emerging evidence that social network interventions can be effective in improving social connections for people with mental health problems. However, further evaluations with robust methodological approaches are required to inform evidence-based recommendations for health services.


Assuntos
Transtorno Depressivo Maior , Transtornos Psicóticos , Adulto , Humanos , Saúde Mental , Narração , Rede Social
4.
BMC Health Serv Res ; 22(1): 1140, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36085063

RESUMO

BACKGROUND: Social integration, shared decision-making and personalised care are key elements of mental health and social care policy. Although these elements have been shown to improve service user and service-level outcomes, their translation into practice has been inconsistent and social isolation amongst service users persists. AIM: To co-adapt, with service users, carers/supporters and health professionals, a web-based social network intervention, GENIE™, for use in secondary mental health services. The intervention is designed to support social activity and preference discussions between mental healthcare professionals and service users as a means of connecting individuals to local resources. METHODS: In Phase 1 (LEARN), we completed two systematic reviews to synthesise the existing evidence relating to the i) effectiveness and ii) the implementation of social network interventions for people with mental health difficulties. We undertook semi-structured interviews with a convenience sample of 15 stakeholders previously involved in the implementation of the intervention in physical healthcare settings. Interviews were also conducted with 5 national key stakeholders in mental health (e.g., policy makers, commissioners, third sector leads) to explore wider implementation issues. In Phase 2 (ADAPT), we worked iteratively with eight service users, nine carers, six professionals/volunteers and our patient and public advisory group. We drew on a framework for experience-based co-design, consisting of a series of stakeholder consultation events, to discuss the use of the social network intervention, in mental health services. Participants also considered factors that could serve as enablers, barriers, and challenges to local implementation. RESULTS: Across the stakeholder groups there was broad agreement that the social network intervention had potential to be useful within mental health services. In terms of appropriate and effective implementation, such an intervention was predicted to work best within the care planning process, on discharge from hospital and within early intervention services. There were indications that the social connection mapping and needs assessment components were of most value and feasible to implement which points to the potential utility of a simplified version compared to the one used in this study. The training provided to facilitators was considered to be more important than their profession and there were indications that service users should be offered the opportunity to invite a carer, friend, or family member to join them in the intervention. CONCLUSION: The GENIE™ intervention has been co-adapted for use in mental health services and a plan for optimal implementation has been co-produced. The next phase of the programme of work is to design and implement a randomised controlled trial to evaluate clinical and cost effectiveness of a simplified version of the intervention.


Assuntos
Cuidadores , Serviços de Saúde Mental , Cuidadores/psicologia , Pessoal de Saúde/psicologia , Humanos , Rede Social , Reino Unido
5.
Trends Mol Med ; 30(4): 301-304, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38462421

RESUMO

Current theoretical understandings of eating disorders often characterize physiological symptoms as secondary consequences driven by core psychological difficulties. This article emphasizes the need to learn from the lived experiences of patients which indicate how biological factors can be central in the development, maintenance, and ultimately the treatment of eating disorders.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Biologia
6.
Clin Child Psychol Psychiatry ; 29(3): 1213-1227, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38290723

RESUMO

Before the COVID-19 pandemic, the prevalence and severity of psychiatric disorders among sexual and gender diverse (SGD) young people was greater than in their heterosexual/cisgender peers. We systematically reviewed literature examining the prevalence, severity, and risk factors for psychiatric disorders among SGD young people aged 25 and under during the pandemic. Four databases (MEDLINE, PsycInfo, Scopus and Web of Science) were searched. Eligibility criteria were studies assessing prevalence rates, mean symptomology scores and risk factors of psychiatric disorders using contemporaneous screening measures or diagnosis. Thirteen studies of mixed quality were identified. Most studies indicated SGD young people were at high risk of experiencing several psychiatric disorders including depressive and generalised anxiety disorder compared to the general population. This group also experienced more severe symptomology of various psychiatric disorders compared to their heterosexual/cisgender peers. Risk factors included those specific to the pandemic along with factors that led to greater risk before the pandemic. This systematic review has indicated evidence of heightened risk of psychiatric disorders among SGD young people during the COVID-19 pandemic. It is important for clinicians to acknowledge the needs of SGD young people, working with them to co-develop more inclusive care as they deal with the pandemic's fallout.


Why was the study done?Before the COVID-19 pandemic, the prevalence and severity of psychiatric disorders in sexual and gender diverse (SGD) young people was greater than in their heterosexual/cisgender peers, based on several risk factors. Research using validated screening measures assessed whether this continued during the pandemic. Yet, these studies have not been brought together in an organised fashion to provide a comprehensive summary of this evidence.What did the researchers do?We reviewed literature examining the prevalence, severity, and risk factors for psychiatric disorders among SGD young people aged 25 and under during the pandemic. Eligibility criteria were studies assessing prevalence rates, mean symptomology scores or risk factors of psychiatric disorders using contemporaneous screening measures or diagnosis.What did the researchers find?Thirteen studies of mixed quality were identified. Most studies indicated SGD young people were more likely to report experiencing several psychiatric disorders including depressive and generalised anxiety disorders compared to the general population. SGD young people also experienced more severe symptomology of various psychiatric disorders compared to their heterosexual/cisgender peers. Risk factors included those specific to the pandemic along with factors that existed before the pandemic.What do the findings mean?This review suggests SGD young people were at greater risk of psychiatric disorders during the COVID-19 pandemic. Clinicians should acknowledge the needs of SGD young people, working with them to co-develop more inclusive care as they deal with the pandemic's fallout.


Assuntos
COVID-19 , Transtornos Mentais , Minorias Sexuais e de Gênero , Humanos , COVID-19/epidemiologia , COVID-19/psicologia , Fatores de Risco , Transtornos Mentais/epidemiologia , Prevalência , Adolescente , Minorias Sexuais e de Gênero/psicologia , Adulto Jovem , Índice de Gravidade de Doença , Feminino , Masculino , Adulto
7.
J Eat Disord ; 12(1): 70, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831456

RESUMO

Eating disorders (EDs) are complex, multifaceted conditions that significantly impact quality-of-life, often co-occur with multiple medical and psychiatric diagnoses, and are associated with a high risk of medical sequelae and mortality. Fortunately, many people recover even after decades of illness, although there are different conceptualisations of recovery and understandings of how recovery is experienced. Differences in these conceptualisations influence categorisations of ED experiences (e.g., longstanding vs. short-duration EDs), prognoses, recommended treatment pathways, and research into treatment outcomes. Within recent years, the proposal of a 'terminal' illness stage for a subset of individuals with anorexia nervosa and arguments for the prescription of end-of-life pathways for such individuals has ignited debate. Semantic choices are influential in ED care, and it is critical to consider how conceptualisations of illness and recovery and power dynamics influence outcomes and the ED 'staging' discourse. Conceptually, 'terminality' interrelates with understandings of recovery, efficacy of available treatments, iatrogenic harm, and complex co-occurring diagnoses, as well as the functions of an individual's eating disorder, and the personal and symbolic meanings an individual may hold regarding suffering, self-starvation, death, health and life. Our authorship represents a wide range of lived and living experiences of EDs, treatment, and recovery, ranging from longstanding and severe EDs that may meet descriptors of a 'terminal' ED to a variety of definitions of 'recovery'. Our experiences have given rise to a shared motivation to analyse how existing discourses of terminality and recovery, as found in existing research literature and policy, may shape the conceptualisations, beliefs, and actions of individuals with EDs and the healthcare systems that seek to serve them.

8.
BJPsych Bull ; : 1-5, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37287111

RESUMO

Eating disorders are historically underserved in healthcare, but are increasingly prevalent and recognised for their high costs regarding mortality, quality of life and the economy. Those with longstanding eating disorders are commonly labelled 'severe and enduring' (SEED), which has been challenged for its conceptual vagueness and potential to discourage patients. Attempts to define individuals from this cohort as having 'terminal' illness have also gained traction in recent years. This paper is grounded in lived/living experience and relevant research. It challenges the logical coherence and utility of SEED, arguing that the word 'enduring' unhelpfully situates intractability of longstanding illness within patients themselves and the nature of their illness. This risks a sense of inevitability and overlooks the important role of contextual factors such as lacking resources and insufficient evidence for withholding active treatment. Recommendations suggest approaches to dismantling unhelpful binaries between early intervention and intensive support, recovery and decline.

9.
Lancet Psychiatry ; 10(2): 146-154, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36697122

RESUMO

The evidence base for the treatment of severe eating disorders is limited. In addition to improving access to early intervention, there is a need to develop more effective treatments for complex presentations of eating disorders. For patients with long-standing and severe illnesses, particular difficulties might exist with their engagement with treatment and achieving treatment outcomes. Alarmingly, there is an emerging international discourse about a concept labelled as terminal anorexia and about the withdrawal of treatment for people with severe eating disorders, resulting in the death of patients, as a legitimate option. This concept has arisen in the context of vastly overstretched specialist services and insufficient research and funding for new treatments. This Personal View combines multiple perspectives from carers, patients, and mental health professionals based in the UK, highlighting how the risks of current service provision are best alleviated by increasing resources, capacity, and training, and not by a narrowing of the criteria according to which patients with eating disorders are offered the care and support they need.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Pacientes , Pessoal de Saúde , Resultado do Tratamento , Cuidadores
10.
Lancet Psychiatry ; 10(3): 220-227, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36696910

RESUMO

The importance of patient and public involvement (PPI) in mental health research is increasingly acknowledged by funders, researchers, and patients. However, the impact of PPI on those who bring their own lived experiences to research environments is underexplored. A retrospective reflective approach was undertaken collaboratively by four people bringing lived experiences of mental health difficulties to a study adapting a social network intervention for mental health services. Authors considered their experiences of involvement and how these affected them personally. We identified six characteristics of involvement that benefit not only research quality, but also people participating in PPI activities: reframing painful memories, recognising value, practising reciprocity, bridging gaps, countering stigma, and challenging established narratives. When designing and conducting research, it is important to engage empathetically with how involvement is experienced by different people. Values should be translated collaboratively into action so that unintended harms might be avoided. This Personal View offers reflections and recommendations to support this process.


Assuntos
Serviços de Saúde Mental , Saúde Mental , Humanos , Estudos Retrospectivos , Participação do Paciente , Dor
11.
J Eat Disord ; 11(1): 25, 2023 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-36805761

RESUMO

BACKGROUND: The concept of control has long been suggested as a central factor in eating disorder (ED) aetiology. The concept is now so mainstream that it risks being used in a potentially reductionist, stigmatising or otherwise harmful manner. In this paper, we explore and discuss our positions on the use of control-related terminology for EDs. METHODS: The authors of this auto-ethnographic position paper include academic researchers, individuals with lived experience and clinicians (not mutually exclusive). In sharing our experiences and observations, we aim to raise awareness of the wider impacts that control framing can have on ED perceptions, treatment, recovery and individuals' lived experience. RESULTS: We argue that although control can play a role in some ED experiences, an overemphasis upon this factor to the exclusion of other conceptualisations is not beneficial. CONCLUSIONS: To mitigate against pathologisation of an individual, it is important to challenge a discourse that can lead to EDs being perceived as something 'wrong' with the individual, rather than a consequence of life events or other environmental influences. We identify priorities for the future for researchers, clinicians, policy makers and the wider public.


Control has often been described as a central factor within Eating Disorders (EDs). Whilst control can play a role in ED experiences, we argue that overemphasis upon this factor can result in other important factors being overlooked. For many individuals, EDs are the consequence of life events and/or other environmental influences. With this in mind, discourse which overemphasises control (e.g., rather than coping) can inaccurately portray EDs as something 'wrong' with the individual. It is important to challenge this discourse to encourage more appropriate perceptions of EDs. In turn, this could improve understanding and treatment of EDs, reduce stigma, and promote recovery.

12.
BJPsych Bull ; : 1-9, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37525957

RESUMO

AIMS/METHOD: This national pre-pandemic survey compared demand and capacity of adult community eating disorder services (ACEDS) with NHS England (NHSE) commissioning guidance. RESULTS: Thirteen services in England and Scotland responded (covering 10.7 million population). Between 2016-2017 and 2019-2020 mean referral rates increased by 18.8%, from 378 to 449/million population. Only 3.7% of referrals were from child and adolescent eating disorder services (CEDS-CYP), but 46% of patients were aged 18-25 and 54% were aged >25. Most ACEDS had waiting lists and rationed access. Many could not provide full medical monitoring, adapt treatment for comorbidities, offer assertive outreach or provide seamless transitions. For patient volume, the ACEDS workforce budget was 15%, compared with the NHSE workforce calculator recommendations for CEDS-CYP. Parity required £7 million investment/million population for the ACEDS. CLINICAL IMPLICATIONS: This study highlights the severe pressure in ACEDS, which has increased since the COVID-19 pandemic. Substantial investment is required to ensure NHS ACEDS meet national guidance, offer evidence-based treatment, reduce risk and preventable deaths, and achieve parity with CEDS-CYP.

13.
Lancet Psychiatry ; 10(6): 452-464, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37182526

RESUMO

Globally, too many people die prematurely from suicide and the physical comorbidities associated with mental illness and mental distress. The purpose of this Review is to mobilise the translation of evidence into prioritised actions that reduce this inequity. The mental health research charity, MQ Mental Health Research, convened an international panel that used roadmapping methods and review evidence to identify key factors, mechanisms, and solutions for premature mortality across the social-ecological system. We identified 12 key overarching risk factors and mechanisms, with more commonalities than differences across the suicide and physical comorbidities domains. We also identified 18 actionable solutions across three organising principles: the integration of mental and physical health care; the prioritisation of prevention while strengthening treatment; and the optimisation of intervention synergies across social-ecological levels and the intervention cycle. These solutions included accessible, integrated high-quality primary care; early life, workplace, and community-based interventions co-designed by the people they should serve; decriminalisation of suicide and restriction of access to lethal means; stigma reduction; reduction of income, gender, and racial inequality; and increased investment. The time to act is now, to rebuild health-care systems, leverage changes in funding landscapes, and address the effects of stigma, discrimination, marginalisation, gender violence, and victimisation.


Assuntos
Transtornos Mentais , Suicídio , Humanos , Mortalidade Prematura , Transtornos Mentais/terapia , Transtornos Mentais/psicologia , Saúde Mental , Atenção à Saúde
14.
Lancet Psychiatry ; 10(12): 966-973, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37769672

RESUMO

The effectiveness of mental health care can be improved through coordinated and wide-scale outcome measurement. The International Consortium for Health Outcomes Measurement has produced collaborative sets of outcome measures for various mental health conditions, but no universal guideline exists for eating disorders. This Position Paper presents a set of outcomes and measures for eating disorders as determined by 24 international experts from professional and lived experience backgrounds. An adapted Delphi technique was used, and results were assessed through an open review survey. Final recommendations suggest outcomes should be tracked across four domains: eating disorder behaviours and cognitions, physical health, co-occurring mental health conditions, and quality of life and social functioning. Outcomes are collected using three to five patient-reported measures. For children aged between 6 years and 12 years, the measures include the Children's Eating Attitude Test (or, for those with avoidant restrictive food intake disorder, the Eating Disorder in Youth Questionnaire), the KIDSCREEN-10, and the Revised Children's Anxiety and Depression Screener-25. For adolescents aged between 13 years and 17 years, the measures include the Eating Disorder Examination Questionnaire (EDE-Q; or, for avoidant restrictive food intake disorder, the Nine-Item Avoidant Restrictive Food Intake Disorder Screener [NIAS]), the two-item Patient Health Questionnaire (PHQ-2), the nine-item Patient Health Questionnaire (PHQ-9), the two-item Generalised Anxiety Disorder (GAD-2), the seven-item Generalised Anxiety Disorder (GAD-7), and the KIDSCREEN-10. For adults older than 18 years, measures include the EDE-Q (or, for avoidant restrictive food intake disorder, the NIAS), the PHQ-2, the PHQ-9, the GAD-2, the GAD-7, the Clinical Impairment Assessment, and the 12-item WHO Disability Assessment Schedule 2.0. These questionnaires should be supplemented by information on patient characteristics and circumstances (ie, demographic, historical, and clinical factors). International adoption of these guidelines will allow comparison of research and clinical interventions to determine which settings and interventions work best, and for whom.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos , Qualidade de Vida , Adulto , Criança , Adolescente , Humanos , Consenso , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Inquéritos e Questionários , Avaliação de Resultados em Cuidados de Saúde
17.
BMJ Open ; 9(6): e027513, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31227535

RESUMO

INTRODUCTION: Care home residents are at increased risk of infections and antibiotic prescription. Reduced antibiotic use from fewer infections would improve quality of life. The Probiotics to Reduce Infections iN CarE home reSidentS (PRINCESS) trial aims to determine the efficacy and investigate mechanisms of daily probiotics on antibiotic use and incidence of infections in care home residents. METHODS AND ANALYSIS: PRINCESS is a double-blind, individually randomised, placebo-controlled trial that will assess the effect of a daily oral probiotic combination of Lactobacillus rhamnosus, GG (LGG) and Bifidobacterium animalis subsp. lactis, BB-12 (BB-12) on cumulative antibiotic administration days (CAADs) (primary outcome) for infection in up to 330 care home residents aged ≥65 years over up to 12 months. Secondary outcomes include: Infection: Total number of days of antibiotic administration for each infection type (respiratory tract infection, urinary tract infection, gastrointestinal infection, unexplained fever and other); number, site, duration of infection; estimation of incidence and duration of diarrhoea and antibiotic-associated diarrhoea; Stool microbiology: Clostridium difficile infection; Gram-negative Enterobacteriaceae and vancomycin-resistant enterococci; LGG and BB-12. Oral microbiology: Candida spp. Health and well-being: Self and/or proxy health-related quality of life EQ5D (5 L); self-and/or proxy-reported ICEpop CAPability measure for older people. Hospitalisations: number and duration of all-cause hospital stays. Mortality: deaths. Mechanistic immunology outcomes: influenza vaccine efficacy (haemagglutination inhibition assay and antibody titres); full blood count and immune cell phenotypes, plasma cytokines and chemokines; cytokine and chemokine response in whole blood stimulated ex vivo by toll-like receptor 2 and 4 agonists; monocyte and neutrophil phagocytosis of Escherichia coli; serum vitamin D. ETHICS AND DISSEMINATION: Ethics approval is from the Wales Research Ethics Committee 3. Findings will be disseminated through peer-reviewed journals and conferences; results will be of interest to patient and policy stakeholders. TRIAL REGISTRATION NUMBER: ISRCTN16392920; Pre-results.


Assuntos
Antibacterianos/farmacologia , Uso de Medicamentos/normas , Serviços de Assistência Domiciliar , Infecções/tratamento farmacológico , Probióticos/administração & dosagem , Qualidade de Vida , Idoso , Método Duplo-Cego , Humanos , Incidência , Infecções/epidemiologia , Reino Unido/epidemiologia
18.
Bioorg Med Chem Lett ; 17(23): 6529-34, 2007 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-17935984

RESUMO

Explorations in the pyrimidinetrione series of MMP-13 inhibitors led to the discovery of a series of spiro-fused compounds that are potent and selective inhibitors of MMP-13. While other spiro-fused motifs are hydrolytically unstable, presumably due to electronic destabilization of the pyrimidinetrione ring, the spiropyrrolidine series does not share this liability. Greater than 100-fold selectivity versus other MMP family members was achieved by incorporation of an extended aryl-heteroaryl P1'group. When dosed as the sodium salt, these compounds displayed excellent oral absorption and pharmacokinetic properties. Despite the selectivity, a representative of this series produced fibroplasia in a 14 day rat study.


Assuntos
Inibidores de Metaloproteinases de Matriz , Inibidores de Proteases/química , Pirimidinas/química , Pirrolidinas/química , Compostos de Espiro/química , Animais , Estabilidade Enzimática/efeitos dos fármacos , Metaloproteinase 13 da Matriz/metabolismo , Inibidores de Proteases/farmacologia , Pirimidinas/farmacologia , Pirrolidinas/farmacologia , Ratos , Compostos de Espiro/farmacologia , Relação Estrutura-Atividade
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