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1.
Psychol Med ; 53(2): 408-418, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-33952358

RESUMO

BACKGROUND: This study aimed to develop, validate and compare the performance of models predicting post-treatment outcomes for depressed adults based on pre-treatment data. METHODS: Individual patient data from all six eligible randomised controlled trials were used to develop (k = 3, n = 1722) and test (k = 3, n = 918) nine models. Predictors included depressive and anxiety symptoms, social support, life events and alcohol use. Weighted sum scores were developed using coefficient weights derived from network centrality statistics (models 1-3) and factor loadings from a confirmatory factor analysis (model 4). Unweighted sum score models were tested using elastic net regularised (ENR) and ordinary least squares (OLS) regression (models 5 and 6). Individual items were then included in ENR and OLS (models 7 and 8). All models were compared to one another and to a null model (mean post-baseline Beck Depression Inventory Second Edition (BDI-II) score in the training data: model 9). Primary outcome: BDI-II scores at 3-4 months. RESULTS: Models 1-7 all outperformed the null model and model 8. Model performance was very similar across models 1-6, meaning that differential weights applied to the baseline sum scores had little impact. CONCLUSIONS: Any of the modelling techniques (models 1-7) could be used to inform prognostic predictions for depressed adults with differences in the proportions of patients reaching remission based on the predicted severity of depressive symptoms post-treatment. However, the majority of variance in prognosis remained unexplained. It may be necessary to include a broader range of biopsychosocial variables to better adjudicate between competing models, and to derive models with greater clinical utility for treatment-seeking adults with depression.


Assuntos
Ansiedade , Depressão , Humanos , Adulto , Depressão/psicologia , Prognóstico , Resultado do Tratamento , Escalas de Graduação Psiquiátrica
2.
BMC Med ; 19(1): 109, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33952286

RESUMO

BACKGROUND: Depression is commonly perceived as a single underlying disease with a number of potential treatment options. However, patients with major depression differ dramatically in their symptom presentation and comorbidities, e.g. with anxiety disorders. There are also large variations in treatment outcomes and associations of some anxiety comorbidities with poorer prognoses, but limited understanding as to why, and little information to inform the clinical management of depression. There is a need to improve our understanding of depression, incorporating anxiety comorbidity, and consider the association of a wide range of symptoms with treatment outcomes. METHOD: Individual patient data from six RCTs of depressed patients (total n = 2858) were used to estimate the differential impact symptoms have on outcomes at three post intervention time points using individual items and sum scores. Symptom networks (graphical Gaussian model) were estimated to explore the functional relations among symptoms of depression and anxiety and compare networks for treatment remitters and those with persistent symptoms to identify potential prognostic indicators. RESULTS: Item-level prediction performed similarly to sum scores when predicting outcomes at 3 to 4 months and 6 to 8 months, but outperformed sum scores for 9 to 12 months. Pessimism emerged as the most important predictive symptom (relative to all other symptoms), across these time points. In the network structure at study entry, symptoms clustered into physical symptoms, cognitive symptoms, and anxiety symptoms. Sadness, pessimism, and indecision acted as bridges between communities, with sadness and failure/worthlessness being the most central (i.e. interconnected) symptoms. Connectivity of networks at study entry did not differ for future remitters vs. those with persistent symptoms. CONCLUSION: The relative importance of specific symptoms in association with outcomes and the interactions within the network highlight the value of transdiagnostic assessment and formulation of symptoms to both treatment and prognosis. We discuss the potential for complementary statistical approaches to improve our understanding of psychopathology.


Assuntos
Depressão , Transtorno Depressivo Maior , Adulto , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Transtornos de Ansiedade , Depressão/diagnóstico , Depressão/epidemiologia , Humanos , Prognóstico
3.
Bull World Health Organ ; 97(2): 154-159, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30728621

RESUMO

PROBLEM: Both sugar-sweetened beverage consumption and the incidence of obesity have increased in the Philippines in recent years. APPROACH: A proposal to tax sugar-sweetened beverages was introduced in the House of Representatives and merged into a proposed comprehensive Tax Reform for Acceleration and Inclusion (TRAIN) Bill to increase the likelihood of acceptance. The health department and finance department recommended a policy that would maximize benefits to both public health and government revenue. To advance discussions, the health department expanded the health argument to include the country's poor performance in oral health. The approved TRAIN Law adopted the term sweetened beverage to emphasize that the tax covers both sugar and non-sugar sweetened beverages. The tax rate was set to 6.00 Philippine pesos (0.111 United States dollars) per litre of sweetened beverages. The sugar industry successfully lobbied for higher tax rates on beverages containing high-fructose corn syrup, resulting in a differential rate of 12.00 Philippine pesos per litre. LOCAL SETTING: Despite a 12% value-added tax on sugar-sweetened beverages, sales had been sustained by enhanced marketing and product variants being offered in small portions. RELEVANT CHANGES: One month after implementation of the tax in 1 January 2018, prices of taxable sweetened beverages had increased by 16.6 to 20.6% and sales in sari-sari (convenience) stores had declined 8.7%. LESSONS LEARNT: The tax benefited from high-level government commitment and support, keeping policy simple reduced opportunities for tax avoidance and evasion, and taking both health and non-health considerations into account were helpful in arguing for the tax.


Assuntos
Bebidas/economia , Política de Saúde/economia , Edulcorantes/economia , Impostos , Diabetes Mellitus/prevenção & controle , Política de Saúde/legislação & jurisprudência , Promoção da Saúde/economia , Promoção da Saúde/métodos , Humanos , Obesidade/prevenção & controle , Filipinas , Avaliação de Programas e Projetos de Saúde , Açúcares/economia , Impostos/legislação & jurisprudência , Organização Mundial da Saúde
4.
Psychol Med ; 41(1): 141-50, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20346195

RESUMO

BACKGROUND: It is important for doctors and patients to know what factors help recovery from depression. Our objectives were to predict the probability of sustained recovery for patients presenting with mild to moderate depression in primary care and to devise a means of estimating this probability on an individual basis. METHOD: Participants in a randomized controlled trial were identified through general practitioners (GPs) around three academic centres in England. Participants were aged >18 years, with Hamilton Depression Rating Scale (HAMD) scores 12-19 inclusive, and at least one physical symptom on the Bradford Somatic Inventory (BSI). Baseline assessments included demographics, treatment preference, life events and difficulties and health and social care use. The outcome was sustained recovery, defined as HAMD score <8 at both 12 and 26 week follow-up. We produced a predictive model of outcome using logistic regression clustered by GP and created a probability tree to demonstrate estimated probability of recovery at the individual level. RESULTS: Of 220 participants, 74% provided HAMD scores at 12 and 26 weeks. A total of 39 (24%) achieved sustained recovery, associated with being female, married/cohabiting, having a low BSI score and receiving preferred treatment. A linear predictor gives individual probabilities for sustained recovery given specific characteristics and probability trees illustrate the range of probabilities and their uncertainties for some important combinations of factors. CONCLUSIONS: Sustained recovery from mild to moderate depression in primary care appears more likely for women, people who are married or cohabiting, have few somatic symptoms and receive their preferred treatment.


Assuntos
Transtorno Depressivo/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Transtorno Depressivo/psicologia , Feminino , Humanos , Modelos Logísticos , Masculino , Estado Civil , Pessoa de Meia-Idade , Atenção Primária à Saúde/estatística & dados numéricos , Escalas de Graduação Psiquiátrica , Indução de Remissão , Fatores Sexuais , Resultado do Tratamento , Adulto Jovem
5.
Diabet Med ; 28(11): 1300-10, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21418098

RESUMO

AIMS: The Illness Perception Questionnaire, the Revised Illness Perception Questionnaire and the Brief Illness Perception Questionnaire have been widely used to measure people's beliefs about diabetes. This review aimed to synthesize evidence on the relationship between the dimensions of the Illness Perception Questionnaire, the Revised Illness Perception Questionnaire and the Brief Illness Perception Questionnaire and HbA(1c) level in adults with diabetes. METHODS: A systematic literature search was carried out in January 2010 to identify relevant studies. Random-effects model meta-analyses were conducted with cross-sectional data to quantify the relationship between Illness Perception Questionnaire dimensions and HbA(1c) across studies. Randomized controlled trials that targeted Illness Perception Questionnaire perceptions and included HbA(1c) as an outcome measure were discussed in a narrative review. RESULTS: Nine cross-sectional studies and four randomized controlled trials were included. Stronger Identity (r+=0.14), Consequences (r+=0.14), Timeline Cyclical (r+ = 0.26) Concern (r+= 0.21), and Emotional Representations (r+=0.18) perceptions had significant positive associations with HbA(1c.) Greater Personal Control (r+=- 0.12) was negatively associated with HbA(1c) . For all relationships, heterogeneity tests were non-significant, suggesting little variability in effect size estimates. Two of the four randomized controlled trials successfully changed illness perceptions, with one also reporting an intervention group reduction in HbA(1c). CONCLUSIONS: Some Illness Perception Questionnaire dimensions had small significant associations with HbA(1c) , although the direction of these associations remains unclear. There was also tentative evidence that illness perceptions can be positively changed through targeted intervention and that these changes may also impact on glycaemic control. Future research could benefit from tailoring intervention content to perceptions that are most highly associated with HbA(1c).


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Hemoglobinas Glicadas/metabolismo , Autocuidado , Adulto , Conscientização , Biomarcadores/sangue , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Autocuidado/estatística & dados numéricos , Inquéritos e Questionários
6.
Epidemiol Psychiatr Sci ; 30: e42, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34085616

RESUMO

AIMS: To determine whether age, gender and marital status are associated with prognosis for adults with depression who sought treatment in primary care. METHODS: Medline, Embase, PsycINFO and Cochrane Central were searched from inception to 1st December 2020 for randomised controlled trials (RCTs) of adults seeking treatment for depression from their general practitioners, that used the Revised Clinical Interview Schedule so that there was uniformity in the measurement of clinical prognostic factors, and that reported on age, gender and marital status. Individual participant data were gathered from all nine eligible RCTs (N = 4864). Two-stage random-effects meta-analyses were conducted to ascertain the independent association between: (i) age, (ii) gender and (iii) marital status, and depressive symptoms at 3-4, 6-8, and 9-12 months post-baseline and remission at 3-4 months. Risk of bias was evaluated using QUIPS and quality was assessed using GRADE. PROSPERO registration: CRD42019129512. Pre-registered protocol https://osf.io/e5zup/. RESULTS: There was no evidence of an association between age and prognosis before or after adjusting for depressive 'disorder characteristics' that are associated with prognosis (symptom severity, durations of depression and anxiety, comorbid panic disorderand a history of antidepressant treatment). Difference in mean depressive symptom score at 3-4 months post-baseline per-5-year increase in age = 0(95% CI: -0.02 to 0.02). There was no evidence for a difference in prognoses for men and women at 3-4 months or 9-12 months post-baseline, but men had worse prognoses at 6-8 months (percentage difference in depressive symptoms for men compared to women: 15.08% (95% CI: 4.82 to 26.35)). However, this was largely driven by a single study that contributed data at 6-8 months and not the other time points. Further, there was little evidence for an association after adjusting for depressive 'disorder characteristics' and employment status (12.23% (-1.69 to 28.12)). Participants that were either single (percentage difference in depressive symptoms for single participants: 9.25% (95% CI: 2.78 to 16.13) or no longer married (8.02% (95% CI: 1.31 to 15.18)) had worse prognoses than those that were married, even after adjusting for depressive 'disorder characteristics' and all available confounders. CONCLUSION: Clinicians and researchers will continue to routinely record age and gender, but despite their importance for incidence and prevalence of depression, they appear to offer little information regarding prognosis. Patients that are single or no longer married may be expected to have slightly worse prognoses than those that are married. Ensuring this is recorded routinely alongside depressive 'disorder characteristics' in clinic may be important.


Assuntos
Antidepressivos , Depressão , Adulto , Antidepressivos/uso terapêutico , Ansiedade , Depressão/diagnóstico , Depressão/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estado Civil , Prognóstico
7.
Eye (Lond) ; 31(9): 1337-1344, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28475181

RESUMO

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the developed world. Monthly or as-needed (PRN) dosing strategies of intravitreal ranibizumab have been established as efficacious treatment options for neovascular AMD. More recently, the 'treat-and-extend' dosing regimen (TREX) is being adopted in clinical practice as it represents a patient-centric and economical option, reducing treatment burden by extending injection intervals when possible. However, the efficacy of TREX using ranibizumab monotherapy remains to be defined. Therefore, we performed a systematic review to assess the current evidence for TREX using ranibizumab by searching MEDLINE, Embase and PubMed. Of the 1733 articles identified, nine TREX studies were included in our analysis (n=748 eyes). Average patient age was 79.25 (range: 77.34-82.00; SD: 7.27). Baseline BCVA ranged from 48.5-68.9 ETDRS letters. BCVA improvement was 8.92 letters at 1 year (range: 6.5-11.5; SD: 7.54), as a weighted mean accounting for numbers of study eyes. The weighted mean number of injections at one year was 8.60 (range: 7.3-12.0; SD: 1.73). Previously, the landmark ANCHOR and MARINA trials reported gains of 11.3 and 7.2 letters, respectively, using monthly ranibizumab. Chin-Yee et al reported a gain of 3.5 ETDRS letters with 5.3 (S.D. 0.66) PRN ranibizumab injections as weighted means at 1 year in their recent systematic review. Our analysis suggests that TREX delivers visual outcomes superior to PRN and approaches similar efficacy to monthly injections. Further RCTs are needed to fully evaluate the efficacy and economy of TREX in the long-term.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Ranibizumab/administração & dosagem , Degeneração Macular Exsudativa/tratamento farmacológico , Esquema de Medicação , Humanos , Injeções Intravítreas , Tomografia de Coerência Óptica , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/fisiopatologia
9.
Oncogene ; 35(16): 2098-111, 2016 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-26212012

RESUMO

Invasion and metastasis are controlled by the invadopodia, which delivers matrix-degrading enzymes to the invasion interface permitting cancer cell penetration and spread into healthy tissue. We have identified a novel pathway that directs Lyn/Src family tyrosine kinase signals to the invadopodia to regulate sarcoma cell invasion via the molecule AFAP-1-like-1 (AFAP1L1), a new member of the AFAP (actin filament-associated protein) family. We show that AFAP1L1 can transform cells, promote migration and co-expression with active Lyn profoundly influences cell morphology and movement. AFAP1L1 intersects several invadopodia pathway components through its multiple domains and motifs, including the following (i) pleckstrin homology domains that bind phospholipids generated at the plasma membrane by phosphoinositide 3-kinase, (ii) a direct filamentous-actin binding domain and (iii) phospho-tyrosine motifs (pY136 and pY566) that specifically bind Vav2 and Nck2 SH2 domains, respectively. These phosphotyrosine motifs are essential for AFAP1L1-mediated cytoskeleton regulation. Through its interaction with Vav2, AFAP1L1 regulates Rac activity and downstream control of PAK1/2/3 (p21-activated kinases) phosphorylation of myosin light chain (MLC) kinase and MLC2. AFAP1L1 interaction with Nck2 recruits actin-nucleating complexes. Significantly, in osteosarcoma cell lines, knockdown of AFAP1L1 inhibits phosphorylated MLC2 recruitment to filamentous-actin structures, disrupts invadopodia formation, cell attachment, migration and invasion. These data define a novel pathway that directs Lyn/Src family tyrosine kinase signals to sarcoma cell invadopodia through specific recruitment of Vav2 and Nck2 to phosphorylated AFAP1L1, to control cell migration and invasion.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Proteínas dos Microfilamentos/fisiologia , Invasividade Neoplásica , Metástase Neoplásica , Fosfotirosina/metabolismo , Sarcoma/patologia , Actinas/metabolismo , Animais , Divisão Celular , Linhagem Celular Tumoral , Humanos , Camundongos , Fosforilação , Sarcoma/metabolismo
10.
Health Technol Assess ; 9(16): 1-134, iii, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15876362

RESUMO

OBJECTIVE: To determine the relative cost-effectiveness of three classes of antidepressants: tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and the modified TCA lofepramine, as first choice treatments for depression in primary care. DESIGN: Open, pragmatic, controlled trial with three randomised arms and one preference arm. Patients were followed up for 12 months. SETTING: UK primary care: 73 practices in urban and rural areas in England. PARTICIPANTS: Patients with a new episode of depressive illness according to GP diagnosis. INTERVENTIONS: Patients were randomised to receive a TCA (amitriptyline, dothiepin or imipramine), an SSRI (fluoxetine, sertraline or paroxetine) or lofepramine. Patients or GPs were able to choose an alternative treatment if preferred. MAIN OUTCOME MEASURES: At baseline the Clinical Interview Schedule, Revised (CIS-R PROQSY computerised version) was administered to establish symptom profiles. Outcome measures over the 12-month follow-up included the Hospital Anxiety and Depression Scale self-rating of depression (HAD-D), CIS-R, EuroQol (EQ-5D) for quality of life, Short Form (SF-36) for generic health status, and patient and practice records of use of health and social services. The primary effectiveness outcome was the number of depression-free weeks (HAD-D less than 8, with interpolation of intervening values) and the primary cost outcome total direct NHS costs. Quality-adjusted life-years (QALYs) were used as the outcome measure in a secondary analysis. Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were computed. Estimates were bootstrapped with 5000 replications. RESULTS: In total, 327 patients were randomised. Follow-up rates were 68% at 3 months and 52% at 1 year. Linear regression analysis revealed no significant differences between groups in number of depression-free weeks when adjusted for baseline HAD-D. A higher proportion of patients randomised to TCAs entered the preference arm than those allocated to the other choices. Switching to another class of antidepressant in the first few weeks of treatment occurred significantly more often in the lofepramine arm and less in the preference arm. There were no significant differences between arms in mean cost per depression-free week. For values placed on an additional QALY of over 5000 pounds, treatment with SSRIs was likely to be the most cost-effective strategy. TCAs were the least likely to be cost-effective as first choice of antidepressant for most values of a depression-free week or QALY respectively, but these differences were relatively modest. CONCLUSIONS: When comparing the different treatment options, no significant differences were found in outcomes or costs within the sample, but when outcomes and costs were analysed together, the resulting cost-effectiveness acceptability curves suggested that SSRIs were likely to be the most cost-effective option, although the probability of this did not rise above 0.6. Choosing lofepramine is likely to lead to a greater proportion of patients switching treatment in the first few weeks. Further research is still needed on the management of depressive illness in primary care. This should address areas such as the optimum severity threshold at which medication should be used; the feasibility and effectiveness of adopting structured depression management programmes in the UK context; the importance of factors such as physical co-morbidity and recent life events in GPs' prescribing decisions; alternative ways of collecting data; and the factors that give rise to many patients being reluctant to accept medication and discontinue treatment early.


Assuntos
Antidepressivos Tricíclicos/economia , Transtorno Depressivo/economia , Lofepramina/economia , Inibidores Seletivos de Recaptação de Serotonina/economia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antidepressivos Tricíclicos/uso terapêutico , Análise Custo-Benefício , Transtorno Depressivo/tratamento farmacológico , Feminino , Humanos , Modelos Lineares , Lofepramina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Qualidade de Vida , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico
11.
Health Technol Assess ; 9(37): 1-104, iii, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16153354

RESUMO

OBJECTIVES: To compare the effectiveness of community mental health nurse (CMHN) problem-solving and generic CMHN care, against usual general practitioner (GP) care in reducing symptoms, alleviating problems, and improving social functioning and quality of life for people living in the community with common mental disorders; and to undertake a cost comparison of each CMHN treatment compared with usual GP care. DESIGN: A pragmatic, randomised controlled trial with three arms: CMHN problem-solving, generic CMHN care and usual GP care. SETTING: General practices in two southern English counties were included in the study. CMHNs were employed by local NHS trusts providing community mental health services. PARTICIPANTS: Participants were GP patients aged 18--65 years with a new episode of anxiety, depression or reaction to life difficulties and had to score at least 3 points on the General Health Questionnaire-12 screening tool. Symptoms had to be present for a minimum of 4 weeks but no longer than 6 months. INTERVENTIONS: Patients were randomised to one of three groups: (1) CMHN problem-solving treatment, (2) generic CMHN treatment, or (3) usual GP care. All three groups of patients remained free to consult their GPs throughout the course of the study, and could be prescribed psychotropic drug treatments. MAIN OUTCOME MEASURES: Patients were assessed at baseline, and 8 weeks and 26 weeks after randomisation. The primary outcome measure was psychological symptoms measured on the Clinical Interview Schedule -- Revised. Other measures included social functioning, health-related quality of life, problem severity and satisfaction. The economic outcomes were evaluated with a cost--utility analysis. RESULTS: Twenty-four CMHNs were trained to provide problem-solving under supervision, and another 29 were referred patients for generic support. In total, 247 patients were randomised to the three arms of the study, referred by 98 GPs in 62 practices. All three groups of patients were greatly improved by the 8-week follow-up. No significant differences were found between the groups at 8 weeks or 26 weeks in symptoms, social functioning or quality of life. Greater satisfaction with treatment was found in the CMHN groups. CMHN care represented a significant additional health service cost and there were no savings in sickness absence. CONCLUSIONS: The study found that specialist mental health nurse support is no better than support from GPs for patients with anxiety, depression and reactions to life difficulties. The results suggest that healthcare providers could consider adopting policies of restricting referrals of unselected patients with common mental disorders to specialist CMHNs, although there may be other roles in primary care that CMHNs could play effectively. Further research should address the predictors of chronicity in common mental disorders and target extra treatment. More research is also needed into the effectiveness and cost-effectiveness of problem-solving treatment for other disorders, of facilitated self-help treatments for common mental disorders and of CMHN care for people with severe and enduring mental illnesses, as well as the prevention of mental disorders.


Assuntos
Ansiedade/enfermagem , Serviços Comunitários de Saúde Mental , Depressão/enfermagem , Medicina de Família e Comunidade , Resolução de Problemas , Adolescente , Adulto , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Relações Enfermeiro-Paciente , Enfermagem Psiquiátrica , Medicina Estatal
12.
J Immunol Methods ; 169(2): 273-85, 1994 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-7510762

RESUMO

A small fraction of affinity-purified MHC class II molecules are known to bind antigenic peptides in vitro. No simple method with acceptable recovery exists for separation of complexes of a known antigenic epitope and MHC class II from empty MHC class II and complexes of MHC class II and endogenously bound peptide. Here we describe an one step metal chelate affinity chromatography method to purify complexes of MHC class II and antigenic peptide of known composition. Complexes of human HLA-DR2 (DRB1*1501/DRB5*0101) and a peptide analog from human myelin basic protein MBP(84-102) containing a 6 histidine tag (6 x His) and a tyrosine residue at the N-terminus end [6 x His-MBP(83-102)Y83] were prepared and purified. The absence of residual free 6 x His-MBP peptide in the complex preparations were confirmed by gel filtration and TLC analyses. The purified complexes were applied onto Ni2+.nitrilotriacetic acid (Ni2+.NTA)-agarose affinity support and 6 x His-tagged peptide class II complexes were selectively eluted with imidazole-containing buffer. The quantitation of bound peptide in the eluted complexes showed 100% occupancy of HLA-DR2 (DRB1*1501/DRB5*0101) with [6 x His-MBP(83-102)Y83] peptide with a recovery of 50-75%. The presence of a single peptide entity in the eluted complexes was confirmed by reverse-phase narrowbore HPLC analysis of the acid-extracted supernatant and by amino acid sequencing analyses. As expected, no endogenous polypeptide was detected in the Ni2+.NTA eluted complexes when analyzed by two-dimensional IEF gel electrophoresis. Finally, we demonstrate that both MBP(84-102) and [6 x His-MBP(83-102)Y83] peptides were equally capable of stimulating restricted T cell line in the presence of autologous antigen presenting cells (APCs). These results demonstrate that metal chelate affinity chromatography can be used to prepare MHC class II-peptide complexes containing single peptide. Such complexes of class II molecules containing known peptide have significant clinical relevance for antigen-specific therapy of various autoimmune diseases and may provide better understanding of the trimolecular interaction between MHC class II, antigenic peptide and T cell receptor (TCR).


Assuntos
Antígenos/isolamento & purificação , Quelantes , Cromatografia de Afinidade/métodos , Antígenos HLA-DR/isolamento & purificação , Níquel , Peptídeos/isolamento & purificação , Sequência de Aminoácidos , Células Apresentadoras de Antígenos , Antígenos/imunologia , Linhagem Celular , Transformação Celular Viral , Cromatografia Líquida de Alta Pressão , Eletroforese em Gel Bidimensional , Antígenos HLA-DR/imunologia , Humanos , Ativação Linfocitária/imunologia , Dados de Sequência Molecular , Proteína Básica da Mielina/imunologia , Proteína Básica da Mielina/isolamento & purificação , Ácido Nitrilotriacético , Linfócitos T/imunologia
13.
Br J Gen Pract ; 49(446): 745-9, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10756621

RESUMO

General practitioners (GPs) need to become more aware of a new generation of antipsychotic drugs that are 'atypical' in that, unlike traditional neuroleptics, they do not cause extrapyramidal side-effects; they may also be more effective against both the positive and negative symptoms of schizophrenia by their actions on various neurotransmitter pathways in the brain. This is a non-systematic review of the development of these new drugs and outlines how they are currently being used. It includes information found from an electronic search of the databases MEDLINE (from 1966 to June 1998) and EMBASE (from 1980 to January 1998) using the combined search terms 'antipsychotic agents', 'atypical', and 'schizophrenia'.


Assuntos
Antipsicóticos/uso terapêutico , Esquizofrenia/tratamento farmacológico , Antipsicóticos/efeitos adversos , Humanos , Tecnologia Farmacêutica
14.
Br J Gen Pract ; 51(469): 655-7, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11510395

RESUMO

Six million informal carers provide support for aged and disabled people in the United Kingdom. Government policies suggest that primary care teams are the main support for carers. This postal survey of 300 general practitioners (GPs) and 272 district nurses (DNs) aimed to determine current practice and views on their role in supporting informal carers. In practice, GPs and DNs lack time, resources, and training to provide support, and see themselves in a reactive role only.


Assuntos
Cuidadores/organização & administração , Enfermagem em Saúde Comunitária/organização & administração , Medicina de Família e Comunidade/organização & administração , Atitude do Pessoal de Saúde , Tamanho das Instituições de Saúde , Humanos , Papel do Médico , Inquéritos e Questionários , Reino Unido
15.
Br J Gen Pract ; 47(421): 515-20, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9302795

RESUMO

The proportion of patients with schizophrenia who lose contact with the secondary services is between 25% and 40%. The general practitioner remains the health care professional most likely to be in contact with such patients. A consensus group of 14 members met on four occasions, reviewed the relevant literature, and developed good-practice guidelines in five areas: establishing a register and organizing regular reviews; comprehensive assessments; information and advice for patients and carers; indications for involving specialist services; and crisis management. The guidelines are presented and their supporting evidence summarized.


Assuntos
Medicina de Família e Comunidade/normas , Guias de Prática Clínica como Assunto , Esquizofrenia/terapia , Conferências de Consenso como Assunto , Humanos , Serviços de Saúde Mental , Reino Unido
16.
Br J Gen Pract ; 48(434): 1560-4, 1998 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9830179

RESUMO

BACKGROUND: Studies have shown that bereaved individuals suffer increased rates of physical and mental ill health. Bereavement support has recently been advocated as an area of prevention in primary care, with suggestions that general practitioners (GPs) should adopt protocols for the active follow-up of their bereaved patients, which relies on the early notification of deaths by hospitals and hospices. Little is known about the routine care currently provided by GPs and primary health care teams (PHCTs) to support their bereaved patients. AIMS: To explore GPs' perceptions of patient death notifications by hospitals and hospices. To describe practice policies relating to patient deaths and the provision of bereavement support. METHOD: Postal questionnaires were sent to senior partners of a random sample of 500 general practices in South Thames Health Region. RESULTS: Three hundred and fifty-three practitioners responded (71%). Hospitals were perceived to be significantly slower than hospices in notifying deaths (P < 0.0001). One hundred and ninety-six practices (56%) kept death registers, 230 (65%) discussed deaths together, and 142 (40%) identified bereaved relatives. One hundred and thirty-seven practices (39%) routinely offered bereaved relatives contact with a PHCT member; while 133 (38%) supported only those who asked for help. Routine support was significantly more likely to be provided by practices that kept a death register, discussed deaths together, identified bereaved relatives, and had a special interest in palliative care. CONCLUSIONS: GPs perceive hospitals to be slower than hospices at notifying deaths, particularly in the first 24 hours. They are divided over whether bereavement support should be proactive or reactive. Keeping a practice death register, discussing deaths together, and identifying newly bereaved relatives are activities related to providing routine bereavement care.


Assuntos
Atitude do Pessoal de Saúde , Luto , Medicina de Família e Comunidade/organização & administração , Cuidados Paliativos na Terminalidade da Vida/organização & administração , Sistemas de Comunicação no Hospital/organização & administração , Médicos de Família/psicologia , Inglaterra , Pesquisas sobre Atenção à Saúde , Cuidados Paliativos na Terminalidade da Vida/normas , Sistemas de Comunicação no Hospital/normas , Humanos , Encaminhamento e Consulta , Inquéritos e Questionários
17.
Br J Gen Pract ; 49(441): 273-6, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10736903

RESUMO

BACKGROUND: Patients seen as 'extras' (or 'fit-ins') are usually given less time for their problems than those in pre-booked appointments. Consequently, long queues of 'extras' should be avoided. AIM: To determine whether a predictable relationship exists between the number of available appointments at the start of the day and the number of extra patients who must be fitted in. This might be used to help plan a practice appointment system. METHOD: Numbers of available appointments at the start of the day and numbers of 'extras' seen were recorded prospectively in 1995 and 1997 in one group general practice. Minimum numbers of available appointments at the start of the day, below which undesirably large numbers of extra patients could be predicted, were determined using logistic regression applied to the 1995 data. Predictive values of the minimum numbers calculated for 1995, in terms of predicting undesirable numbers of 'extras', were then determined when applied to the 1997 data. RESULTS: Numbers of extra patients seen correlated negatively with available appointments at the start of the day for all days of the week, with coefficients ranging from -0.66 to -0.80. Minimum numbers of available appointments below which undesirably large numbers of extras could be predicted were 26 for Mondays and four for the other week-days. When applied to 1997 data, these minimum numbers gave positive and negative predictive values of 76% and 82% respectively, similar to their values for 1995, despite increases in patient attendance and changes in the day-to-day pattern of surgery provision between the two years. CONCLUSION: A predictable relationship exists between the number of available appointments at the start of the day and the number of extras who must be fitted in, which may be used to help plan the appointment system for some years ahead, at least in this relatively stable suburban practice.


Assuntos
Agendamento de Consultas , Medicina de Família e Comunidade/organização & administração , Administração da Prática Médica/organização & administração , Coleta de Dados/métodos , Medicina de Família e Comunidade/economia , Medicina de Família e Comunidade/estatística & dados numéricos , Modelos Logísticos , Reino Unido
18.
Br J Gen Pract ; 44(384): 301-5, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8068376

RESUMO

BACKGROUND: Increasing numbers of long-term mentally ill people now live in the community, many of whom lose contact with psychiatric services and come to depend on general practitioners for medical care. However, it has been suggested that general practitioners may be unaware of some of these patients and their needs. AIM: This study set out to investigate the care received by this group of patients. METHOD: Case registers of adults disabled by long-term mental illness were set up in 16 of 110 group general practices asked to participate. A search of each practice's record systems was combined with a survey of local psychiatric and social service teams, to seek practice patients who might not be identified from the general practice data. RESULTS: Of the 440 patients found, 90% were identified from information within the practices, mainly computerized repeat prescription and diagnostic data. The other 10% were identified only by psychiatric services. Over one third of the patients had no current contact with psychiatric services. Patients in contact with psychiatric services had been ill for a shorter time than those not in contact. More patients suffering from psychotic illnesses were in current contact than those with non-psychotic diagnoses. Over 90% of the patients had been seen by their general practitioners within 12 months, on average eight times. Most consultations were for minor physical disorders, repeat prescriptions and sickness certificates. Elements of the formal mental state examination were recorded in one third of cases and adjustments of psychotropic medication in one fifth. CONCLUSION: These findings suggest that patients in long-term contact with specialist services cannot be taken as representative of the whole population with long-term mental illness. General practitioners could use their frequent contacts with long-term mentally ill people to play a greater role in monitoring the mental state and drug treatment of this group.


Assuntos
Serviços Comunitários de Saúde Mental/estatística & dados numéricos , Medicina de Família e Comunidade/estatística & dados numéricos , Transtornos Mentais/terapia , Continuidade da Assistência ao Paciente , Pessoas com Deficiência , Inglaterra , Feminino , Humanos , Assistência de Longa Duração , Masculino , Pessoa de Meia-Idade
19.
Br J Gen Pract ; 50(454): 380-3, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10897535

RESUMO

BACKGROUND: Early detection and management of patients with eating disorders is thought to improve prognosis, yet little is known about the factors associated with referral of these patients to treatment centres. AIM: To calculate general practitioner (GP) referral rates to a specialist eating disorder service and determine the association between referral rate and general practice and practitioner factors. METHOD: Referral rate was calculated from a database of routine referrals to St George's Hospital Eating Disorder Service from January 1990 to May 1996 and correlated with practice and practitioner details obtained from medical directories and health authority data. RESULTS: There was a wide variation in referral rates. A higher referral rate was found to be associated with practice size, proximity to the clinic, female GPs, GPs having the MRCGP qualification, being United Kingdom qualified, and offering full contraceptive services. Fundholding was associated with lower rates of referral. CONCLUSION: Patients with eating disorders may be at a disadvantage in certain practices. Educational interventions could be targeted towards low referrals.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Padrões de Prática Médica/estatística & dados numéricos , Encaminhamento e Consulta/estatística & dados numéricos , Adolescente , Adulto , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Médicos de Família/educação , Encaminhamento e Consulta/economia , Fatores Sexuais , Reino Unido/epidemiologia
20.
Br J Gen Pract ; 50(451): 121-6, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10750209

RESUMO

BACKGROUND: Around 25% of patients with psychoses lose contact with specialist psychiatric services, despite the government's policy to focus the efforts of community teams on this group. AIM: To identify patient and practice factors associated with continuing contact and loss of contact with specialist services. METHOD: Cross-sectional comparison was made of patients in and out of specialist contact, through detailed interviews with 102 patients among 26 south west London practices. Associations were sought between contact with specialist services and patient factors (illness severity, social functioning, quality of life, needs for care, and satisfaction with general practitioner [GP] services) and practice factors (size, location, fundholding status, training status, and the presence of mental health professionals on site). RESULTS: Thirty-one (30%) patients were currently out of specialist contact. No significant differences were found between those in and out of contact on any measures of diagnosis or psychiatric history. Those in contact had significantly more symptoms, poorer social functioning, poorer quality of life, and more needs for care. The proportion out of contact was significantly higher in two practices that had employed their own mental health professionals to provides services on site for severe mental illnesses. Two factors remained significant predictors of contact in a logistic regression model: whether or not the patient's practice offered a special service on site, and greater patient needs for care. CONCLUSIONS: Secondary mental health services are being targeted towards the more needy patients. The provision of special services in practices can shift care further away from secondary care while still meeting patients' needs.


Assuntos
Serviços Comunitários de Saúde Mental/provisão & distribuição , Medicina de Família e Comunidade/organização & administração , Avaliação das Necessidades , Atenção Primária à Saúde/organização & administração , Transtornos Psicóticos/terapia , Análise de Variância , Serviços Comunitários de Saúde Mental/organização & administração , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde/economia , Transtornos Psicóticos/reabilitação , Análise de Regressão , Reino Unido
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