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INTRODUCTION: The UK National Haemophilia Database (NHD) collects data from all UK persons with haemophilia A with inhibitors (PwHA-I). It is well-placed to investigate patient selection, clinical outcomes, drug safety and other issues not addressed in clinical trials of emicizumab. AIMS: To determine safety, bleeding outcomes and early effects on joint health of emicizumab prophylaxis in a large, unselected cohort using national registry and patient reported Haemtrack (HT) data between 01 January 2018 and 30 September 2021. METHODS: Prospectively collected bleeding outcomes were analysed in people with ≥6 months emicizumab HT data and compared with previous treatment if available. Change in paired Haemophilia Joint Health Scores (HJHS) were analysed in a subgroup. Adverse events (AEs) reports were collected and adjudicated centrally. RESULTS: This analysis includes 117 PwHA-I. Mean annualised bleeding rate (ABR) was .32 (95% CI, .18; .39) over a median 42 months treatment with emicizumab. Within-person comparison (n = 74) demonstrated an 89% reduction in ABR after switching to emicizumab and an increase in zero treated bleed rate from 45 to 88% (p < .01). In a subgroup of 37 people, total HJHS improved in 36%, remained stable in 46% and deteriorated in 18%, with a median (IQR) within-person change of -2.0 (-9, 1.5) (p = .04). Three arterial thrombotic events were reported, two possibly drug related. Other AEs were generally non-severe and usually limited to early treatment, included cutaneous reactions (3.6%), headaches (1.4%), nausea (2.8%) and arthralgia (1.4%). CONCLUSIONS: Emicizumab prophylaxis is associated with sustained low bleeding rates and was generally well-tolerated in people with haemophilia A and inhibitors.
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Anticuerpos Biespecíficos , Hemofilia A , Humanos , Hemofilia A/complicaciones , Hemofilia A/tratamiento farmacológico , Estudios de Seguimiento , Anticuerpos Biespecíficos/efectos adversos , Hemorragia/complicaciones , Reino Unido , Factor VIII/uso terapéuticoRESUMEN
OBJECTIVES: To report the 12-month prevalence of joint bleeds from the National Haemophilia Database (NHD) and Haemtrack, a patient-reported online treatment diary and concurrent joint disease status using the haemophilia joint health score (HJHS) at individual joint level, in children and adults with severe haemophilia A and B (HA/HB) without a current inhibitor. DESIGN: A 2018 retrospective database study of NHD from which 2238 cases were identified, 463 patients had fully itemised HJHS of whom 273 were compliant in recording treatment using Haemtrack. SETTING: England, Wales and Scotland, UK. PARTICIPANTS: Children (<18 years) and adults (≥18 years) with severe HA and HB (factor VIII/factor IX, <0.01 iu/mL) without a current inhibitor. PRIMARY AND SECONDARY OUTCOMES: Prevalence of joint haemarthrosis and concurrent joint health measured using the HJHS. RESULTS: The median (IQR) age of children was 10 (6-13) and adults 40 (29-50) years. Haemarthrosis prevalence in HA/HB children was 33% and 47%, respectively, and 60% and 42%, respectively, in adults. The most common site of haemarthrosis in children was the knee in HA and ankle in HB. In adults, the incidence of haemarthrosis at the ankles and elbows was equal. The median total HJHS in HA/HB children was 0 and in adults with HA/HB, were 18 and 11, respectively. In adults with HA/HB, the median ankle HJHS of 4.0 was higher than the median HJHS of 1.0 for both the knee and elbow. CONCLUSION: Despite therapeutic advances, only two-thirds of children and one-third of adults were bleed-free, even in a UK cohort selected for high compliance with prophylaxis. The median HJHS of zero in children suggests joint health is relatively unaffected during childhood. In adults, bleed rates were highest in ankles and elbows, but the ankles led to substantially worse joint health scores.
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Hemofilia A , Adulto , Niño , Hemartrosis/complicaciones , Hemartrosis/epidemiología , Hemofilia A/complicaciones , Hemofilia A/tratamiento farmacológico , Hemofilia A/epidemiología , Humanos , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Prevalencia , Estudios Retrospectivos , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Bleeding of unknown cause (BUC) and unclassified bleeding disorders (UBD) are increasingly recognized. There is no guidance on diagnosis and management. OBJECTIVES: To examine UK haemophilia centre registration patterns and current practice for UBD patients. METHODS: In a two-step process, the UK National Haemophilia Database (NHD) was reviewed for registration patterns of UBD patients and a survey of UK haemophilia centers was conducted (January/February 2021) to capture current practice for diagnosis and management of patients with UBD. RESULTS/DISCUSSION: Overall, registrations with the NHD for UBD patients has sharply risen from 2012 to 2020 and in 2019 accounted for 2.65% of registered patients. For the survey, the response rate was 52/67 (78%). Practice was widely variable; 35/52 (67%) centers register UBD; among these 35 centers, terminology included UBD (28 centers), undiagnosed bleeding disorder (four centers), and BUC (three centers); 34/52 (65%) centers use a formal bleeding assessment tool. For management of dental extraction and high bleeding risk surgery in a fictional UBD patient we found that tranexamic acid was widely used; however, beyond this a variety of hemostatic products were advised including blood products, recombinant factor VIIa/prothrombin complex concentrate, and desmopressin. There was general consensus (≈90%) on avoiding regional anesthesia in pregnancy, but no agreement on the need for fetal precautions to avoid bleeding at delivery (50% would advise these). There was a disparity of opinion on chemical thromboprophylaxis, and management of patients without prior hemostatic challenges and offspring of these patients. CONCLUSION: This study provides a snapshot of current practice and real-world data in this area. Future studies need to address the gaps in evidence.
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Hemofilia A , Ácido Tranexámico , Tromboembolia Venosa , Anticoagulantes , Femenino , Hemofilia A/diagnóstico , Hemofilia A/tratamiento farmacológico , Hemofilia A/epidemiología , Humanos , Embarazo , Reino Unido/epidemiologíaRESUMEN
INTRODUCTION: In good risk patients (historic inhibitor peak < 200BU), the International Immune Tolerance Study demonstrated equal efficacy to induce tolerance between high (200iu/kg/day) and low dose (50iu/kg ×3 times/week) immune tolerance induction (ITI) regimens. However, the trial stopped early on account of the excessive bleed rate in the low dose ITI arm. METHODS: United Kingdom Haemophilia Centre Doctors' Organization (UKHCDO) Paediatric and Inhibitor working parties considered available ITI data alongside the bi-phenotypic antibody emicizumab (Hemlibra®) efficacy and safety data to develop a consensus guideline for the future UK ITI guideline. RESULTS: This revision of UKHCDO ITI guidance incorporates the recommendation to use emicizumab as a prophylaxis haemostatic agent to reduce bleeding rates and to facilitate low dose and reduced frequency of FVIII CFC for ITI in the majority of children. CONCLUSION: This consensus protocol will facilitate future evaluation of ITI outcomes in the evolving landscape of haemophilia therapeutics and ITI strategies.
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Hemofilia A , Niño , Factor VIII , Hemofilia A/tratamiento farmacológico , Hemorragia/prevención & control , Humanos , Tolerancia Inmunológica , Reino UnidoRESUMEN
INTRODUCTION: Standard treatment of congenital haemophilia A is based on replacement therapy with coagulation factor VIII (FVIII) products. A major complication of FVIII therapy is the occurrence of IgG alloantibodies (inhibitors) that neutralize FVIII activity. AIM: The aim of the analysis was estimating the risk of high-titre inhibitor associated with the second-generation full-length product compared to third-generation full-length product and other recombinant FVIII (rFVIII). METHODS: We conducted a combined analysis of individual patient data from three large studies in previously untreated patients (PUPs) with severe haemophilia A. RESULTS: A total of 1109 PUPs were treated from 1993 to 2013 including 787 PUPs treated from 2004 onwards (primary analysis cohort). A total of 322 patients (29.0%) developed an inhibitor, of which 192 (17.3%) a high-titre inhibitor. In the primary analysis set, 29.9% of patients developed an inhibitor and 17.2% a high-titre inhibitor. The combined analysis indicated a lower risk of high-titre inhibitor development for the third-generation rFVIII product compared to the second-generation rFVIII product (primary analysis: adjusted hazard ratio (HR) = 0.72, 95% CI: 0.49 to 1.06). Adjusted HR for all inhibitor development was significantly lower for the third-generation product compared to the second-generation product. CONCLUSION: The trend of an increased risk of inhibitor development in PUPs for one recombinant product illustrates that extrapolation from one recombinant factor VIII product to other products might not be justified.
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Factor VIII/inmunología , Factor VIII/uso terapéutico , Hemofilia A/tratamiento farmacológico , Hemofilia A/inmunología , Proteínas Recombinantes/uso terapéutico , Humanos , Factores de RiesgoRESUMEN
BACKGROUND: Temperature is one of the most important abiotic factors limiting plant growth and productivity. Many plants exhibit cold acclimation to prepare for the likelihood of freezing as temperatures decrease towards 0 °C. The physiological mechanisms associated with enabling increased tolerance to sub-zero temperatures vary between species and genotypes. Geographically and climatically diverse populations of Arabidopsis lyrata ssp. petraea were examined for their ability to survive, maintain functional photosynthetic parameters and cellular electrolyte leakage integrity after being exposed to sub-zero temperatures. The duration of cold acclimation prior to sub-zero temperatures was also manipulated (2 and 14 days). RESULTS: We found that there was significant natural variation in tolerances to sub-zero temperatures among populations of A. petraea. The origin of the population affected the acclimation response and survival after exposure to sub-zero temperatures. Cold acclimation of plants prior to sub-zero temperatures affected the maximum quantum efficiency of photosystem II (PSII) (Fv/Fm) in that plants that were cold acclimated for longer periods had higher values of Fv/Fm as a result of sub-zero temperatures. The inner immature leaves were better able to recover Fv/Fm from sub-zero temperatures than mature outer leaves. The Irish population (Leitrim) acclimated faster, in terms of survival and electrolyte leakage than the Norwegian population (Helin). CONCLUSION: The ability to survive, recover photosynthetic processes and cellular electrolyte leakage after exposure to sub-zero temperatures is highly dependent on the duration of cold acclimation.
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Aclimatación , Arabidopsis/fisiología , Clorofila/metabolismo , Fluorescencia , Congelación , Fotosíntesis/fisiología , Complejo de Proteína del Fotosistema II/metabolismo , Hojas de la Planta/fisiologíaRESUMEN
Inhibitor formation in non-severe haemophilia A is a life-long risk and associated with morbidity and mortality. There is a paucity of data to understand real-world inhibitor screening practice. We evaluated the treatment burden, haemostatic strategies, F8 genotyping and inhibitor screening practices in non-severe haemophilia A in seven London haemophilia centres. In the 2-year study period, 44% (377/853) patients received at least one haemostatic treatment. Seventy-nine percent of those treated (296/377) received factor VIII (FVIII) concentrate. F8 genotype was known in 88% (331/377) of individuals. Eighteen per cent (58/331) had 'high-risk' F8 genotypes. In patients with 'standard-risk' F8 genotypes treated on-demand with FVIII concentrate, 51·3% episodes (243/474) were screened within 1 year. However, poor screening compliance was observed after 'high-risk' treatment episodes. In patients with 'standard-risk' F8 genotypes, 12·3% (28/227) of treatment episodes were screened in the subsequent 6 weeks after surgery or a bleed requiring ≥5 exposure days. Similarly, in the context of 'high-risk' F8 genotypes after any FVIII exposure, only 13·6% (12/88) of episodes were screened within 6 weeks. Further study is required to assess optimal practice of inhibitor screening in non-severe haemophilia A to inform subsequent clinical decisions and provide more robust prevalence data to further understand the underlying immunological mechanism.
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Factor VIII/genética , Genotipo , Hemofilia A/inmunología , Hemofilia A/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Hemofilia A/genética , Hemostáticos/uso terapéutico , Humanos , Lactante , Tamizaje Masivo/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Adulto JovenRESUMEN
Antibody formation to factor VIII (FVIII) remains the greatest clinical and diagnostic challenge to the haemophilia-treating physician. Current guidance for testing for inhibitory FVIII antibodies (inhibitors) recommends the functional Nijmegen-Bethesda assay (NBA). A FVIII ELISA offers a complementary, immunological approach for FVIII antibody testing. It was the aim of this study to retrospectively evaluate the performance of a FVIII ELISA (index) for detection of FVIII antibodies, compared with the NBA (reference). All samples sent for routine FVIII antibody testing at two haemophilia Comprehensive Care Centres, were tested in parallel using the NBA and a solid-phase, indirect FVIII ELISA kit (Immucor). A total of 497 samples from 239 patients (severe haemophilia A=140, non-severe haemophilia A=85, acquired haemophilia A=14) were available for analysis. Sixty-three samples tested positive by the NBA (prevalence 12.7%, 95% confidence interval [CI], 9.9-15.9 %), with a median inhibitor titre of 1.2 BU/ml (range 0.7-978.0). The FVIII ELISA demonstrated a specificity of 94.0% (95%CI, 91.3-96.0), sensitivity of 77.8% (95%CI, 65.5-87.3), negative predictive value of 96.7% (95%CI, 94.5-98.2), positive predictive value 65.3% (95%CI, 53.5-76.0), negative likelihood ratio 0.2 (95%CI, 0.1-0.4), positive likelihood ratio 13.0 (95%CI, 8.7-19.3) and a diagnostic odds ratio of 54.9 (95%CI, 27.0-112.0). Strong positive correlation (r=0.77, p<0.001) was seen between the results of the NBA (log adjusted) and FVIII ELISA optical density. In conclusion, FVIII ELISA offers a simple, specific, surveillance method enabling batch testing of non-urgent samples for the presence of FVIII antibodies.
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Autoanticuerpos/sangre , Coagulantes/inmunología , Ensayo de Inmunoadsorción Enzimática , Factor VIII/inmunología , Hemofilia A/diagnóstico , Análisis de Varianza , Biomarcadores/sangre , Coagulantes/uso terapéutico , Factor VIII/uso terapéutico , Hemofilia A/sangre , Hemofilia A/tratamiento farmacológico , Hemofilia A/genética , Hemofilia A/inmunología , Humanos , Funciones de Verosimilitud , Londres , Variaciones Dependientes del Observador , Oportunidad Relativa , Valor Predictivo de las Pruebas , Juego de Reactivos para Diagnóstico , Reproducibilidad de los Resultados , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
The age-adjusted incidence of new factor VIII inhibitors was analyzed in all United Kingdom patients with severe hemophilia A between 1990 and 2009. Three hundred fifteen new inhibitors were reported to the National Hemophilia Database in 2528 patients with severe hemophilia who were followed up for a median (interquartile range) of 12 (4-19) years. One hundred sixty (51%) of these arose in patients ≥ 5 years of age after a median (interquartile range) of 6 (4-11) years' follow-up. The incidence of new inhibitors was 64.29 per 1000 treatment-years in patients < 5 years of age and 5.31 per 1000 treatment-years at age 10-49 years, rising significantly (P = .01) to 10.49 per 1000 treatment-years in patients more than 60 years of age. Factor VIII inhibitors arise in patients with hemophilia A throughout life with a bimodal risk, being greatest in early childhood and in old age. HIV was associated with significantly fewer new inhibitors. The inhibitor incidence rate ratio in HIV-seropositive patients was 0.32 times that observed in HIV-seronegative patients (P < .001). Further study is required to explore the natural history of later-onset factor VIII inhibitors and to investigate other potential risk factors for inhibitor development in previously treated patients.
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Inhibidores de Factor de Coagulación Sanguínea/sangre , Factor VIII/antagonistas & inhibidores , Hemofilia A/sangre , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Bases de Datos Factuales , Femenino , Seropositividad para VIH/sangre , Seropositividad para VIH/epidemiología , Seropositividad para VIH/terapia , Hemofilia A/epidemiología , Hemofilia A/terapia , Humanos , Incidencia , Masculino , Estudios Retrospectivos , Factores de Riesgo , Reino UnidoRESUMEN
Comparisons of psychiatric patients who die by suicide using different methods are scarce. We aimed to establish the methods of suicide used by those who are currently or have recently been in contact with mental health services in England and Wales (N = 6,203), and describe the social and clinical characteristics of suicides by different methods. We found that hanging, self-poisoning, and jumping (from a height or in front of a moving vehicle) were the most common methods of suicide, accounting for 79% of all deaths. The implications of these and other findings are discussed.
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Trastornos Mentales/epidemiología , Suicidio , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , Inglaterra/epidemiología , Femenino , Humanos , Masculino , Trastornos Mentales/terapia , Persona de Mediana Edad , Factores Sexuales , Factores Socioeconómicos , Encuestas y Cuestionarios , Gales/epidemiología , Adulto JovenRESUMEN
Cells associated with veins of petioles of C(3) tobacco possess high activities of the decarboxylase enzymes required in C(4) photosynthesis. It is not clear whether this is the case in other C(3) species, nor whether these enzymes provide precursors for specific biosynthetic pathways. Here, we investigate the activity of C(4) acid decarboxylases in the mid-vein of Arabidopsis, identify regulatory regions sufficient for this activity, and determine the impact of removing individual isoforms of each protein on mid-vein metabolite profiles. This showed that radiolabelled malate and bicarbonate fed to the xylem stream were incorporated into soluble and insoluble material in the mid-vein of Arabidopsis leaves. Compared with the leaf lamina, mid-veins possessed high activities of NADP-dependent malic enzyme (NADP-ME), NAD-dependent malic enzyme (NAD-ME) and phosphoenolpyruvate carboxykinase (PEPCK). Transcripts derived from both NAD-ME, one PCK and two of the four NADP-ME genes were detectable in these veinal cells. The promoters of each decarboxylase gene were sufficient for expression in mid-veins. Analysis of insertional mutants revealed that cytosolic NADP-ME2 is responsible for 80% of NADP-ME activity in mid-veins. Removing individual decarboxylases affected the abundance of amino acids derived from pyruvate and phosphoenolpyruvate. Reducing cytosolic NADP-ME activity preferentially affected the sugar content, whereas abolishing NAD-ME affected both the amino acid and the glucosamine content of mid-veins.
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Aminoácidos/metabolismo , Arabidopsis/enzimología , Arabidopsis/metabolismo , Metabolismo de los Hidratos de Carbono/fisiología , Fotosíntesis/fisiología , Arabidopsis/genética , Metabolismo de los Hidratos de Carbono/genética , Radioisótopos de Carbono/metabolismo , Cromatografía en Capa Delgada , Malato Deshidrogenasa/genética , Malato Deshidrogenasa/fisiología , Malatos/metabolismo , Mutagénesis Insercional , Fosfoenolpiruvato Carboxilasa/genética , Fosfoenolpiruvato Carboxilasa/fisiología , Fotosíntesis/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , XilemaRESUMEN
Cells associated with veins of C(3) species often contain significant amounts of chlorophyll, and radiotracer analysis shows that carbon present in the transpiration stream may be used for photosynthesis in these cells. It is not clear whether CO2 is also supplied to these cells close to veins via stomata, nor whether this veinal photosynthesis supplies carbon skeletons to particular metabolic pathways. In addition, it has not been possible to determine whether photosynthesis in cells close to veins of C(3) plants is quantitatively important for growth or fitness. To investigate the role of photosynthesis in cells in and around the veins of C(3) plants, we have trans-activated a hairpin construct to the chlorophyll synthase gene (CS) using an Arabidopsis thaliana enhancer trap line specific to veins. CS is responsible for addition of the phytol chain to the tetrapyrolle head group of chlorophyll, and, as a result of cell-specific trans-activation of the hairpin to CS, chlorophyll accumulation is reduced around veins. We use these plants to show that, under steady-state conditions, the extent to which CO2 is supplied to cells close to veins via stomata is limited. Fixation by minor veins of CO2 supplied to the xylem stream and the amount of specific metabolites associated with carbohydrate metabolism and the shikimate pathway were all reduced. In addition, an abundance of transcripts encoding components of pathways that generate phosphoenolpyruvate were altered. Leaf senescence, growth rate and seed size were all reduced in the lines with lower photosynthetic ability in veins and in cells close to veins.
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Arabidopsis/fisiología , Clorofila/biosíntesis , Fotosíntesis , Ácido Shikímico/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Metabolismo de los Hidratos de Carbono , Dióxido de Carbono/metabolismo , Ligasas de Carbono-Oxígeno/genética , Ligasas de Carbono-Oxígeno/metabolismo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo , Plantas Modificadas Genéticamente/fisiología , Interferencia de ARN , ARN de Planta/metabolismoRESUMEN
BACKGROUND: Self-harm is a major healthcare problem in the United Kingdom, but monitoring of hospital presentations has largely been done separately in single centres. Multicentre monitoring of self-harm has been established as a result of the National Suicide Prevention Strategy for England. METHOD: Data on self-harm presentations to general hospitals in Oxford (one hospital), Manchester (three hospitals) and Leeds (two hospitals), collected through monitoring systems in each centre, were analysed for the 18-month period March 2000 to August 2001. RESULTS: The findings were based on 7344 persons who presented following 10,498 episodes of self-harm. Gender and age patterns were similar in the three centres, 57.0% of patients being female and two-thirds (62.9%) under 35 years of age. The largest numbers by age groups were 15-19 year-old females and 20-24 year-old males. The female to male ratio decreased with age. Rates of self-harm were higher in Manchester than Oxford or Leeds, in keeping with local suicide rates. The proportion of patients receiving a specialist psychosocial assessment varied between centres and was strongly associated with admission to the general hospital. Approximately 80% of self-harm involved self-poisoning. Overdoses of paracetamol, the most frequent method, were more common in younger age groups, antidepressants in middle age groups, and benzodiazepines and sedatives in older age groups. Alcohol was involved in more than half (54.9%) of assessed episodes. The most common time of presentation to hospital was between 10 pm and 2 am. CONCLUSIONS: Multicentre monitoring of self-harm in England has demonstrated similar overall patterns of self-harm in Oxford, Manchester and Leeds, with some differences reflecting local suicide rates. Diurnal variation in time of presentation to hospital and the need for assessment of non-admitted patients have implications for service provision.
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Conducta Autodestructiva/epidemiología , Conducta Autodestructiva/psicología , Acetaminofén/envenenamiento , Adolescente , Adulto , Distribución por Edad , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/psicología , Analgésicos no Narcóticos/envenenamiento , Antidepresivos/envenenamiento , Recolección de Datos , Sobredosis de Droga/epidemiología , Sobredosis de Droga/psicología , Servicio de Urgencia en Hospital , Inglaterra/epidemiología , Femenino , Humanos , Hipnóticos y Sedantes/envenenamiento , Masculino , Servicio de Psiquiatría en Hospital , Distribución por Sexo , Factores Socioeconómicos , Intento de Suicidio/psicología , Intento de Suicidio/estadística & datos numéricos , TiempoRESUMEN
OBJECTIVE: To compare the cost-effectiveness of generic psychological therapy (counseling) with routinely prescribed antidepressant drugs in a naturalistic general practice setting for a follow-up period of 12 months. METHODS: Economic analysis alongside a randomized clinical trial with patient preference arm. Comparison of depression-related health service costs at 12 months. Cost-effectiveness analysis of bootstrapped trial data using net monetary benefits and acceptability curves. RESULTS: No significant difference between the mean observed costs of patients randomized to antidepressants or to counseling (342 pounds sterling vs 302 pounds sterling , p = .56 [t test]). If decision makers are not willing to pay more for additional benefits (value placed on extra patient with good outcome, denoted by K, is zero), then we find little difference between the treatment modalities in terms of cost-effectiveness. If decision makers do place value on additional benefit (K > 0 pounds sterling), then the antidepressant group becomes more likely to be cost-effective. This likelihood is in excess of 90% where decision makers are prepared to pay an additional 2,000 pounds sterling or more per additional patient with a good global outcome. The mean values for incremental net monetary benefits (INMB) from antidepressants are substantial for higher values of K (INMB = 406 pounds sterling when K = 2,500 pounds sterling). CONCLUSION: For a small proportion of patients, the counseling intervention (as specified in this trial) is a dominant cost-effective strategy. For a larger proportion of patients, the antidepressant intervention (as specified in this trial) is the dominant cost-effective strategy. For the remaining group of patients, cost-effectiveness depends on the value of K. Since we cannot observe K, acceptability curves are a useful way to inform decision makers.
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Antidepresivos/economía , Trastorno Depresivo/terapia , Costos de la Atención en Salud , Atención Primaria de Salud/economía , Psicoterapia/economía , Antidepresivos/uso terapéutico , Análisis Costo-Beneficio , Consejo/economía , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/economía , Investigación sobre Servicios de Salud , Humanos , Medicina Estatal , Reino UnidoRESUMEN
BACKGROUND: A major shortcoming of current research into personality is its failure to explore the relationship between theories of general personality and mental disorder. AIMS: To provide preliminary data to address this deficit. METHOD: In the first of two studies, we examined the relationship between the Neuroticism, Extraversion and Other - Five-Factor Inventory (NEO-FFI) and DSM personality disorders in a consecutive series of mentally disordered offenders. In the second, we sought to separate the personality dimension neuroticism from symptoms of depressive disorder in a sample of subjects with current depression. RESULTS: Factors from the NEO-FFI were associated with different personality disorders in a predictable manner (first study). It was possible to identify a component of neuroticism (i.e. 'worry') that could be separated from depressive symptoms (second study). CONCLUSIONS: Theories of general personality theory can enlighten and refine descriptions of abnormal mental states by informing both their aetiology and their prognosis.