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BACKGROUND: Urgent dental care may be the only place where many people, especially vulnerable groups, access care. This presents an opportunity for delivery of a behavioural intervention promoting planned dental visiting, which may help address one of the factors contributing to a socio-economic gradient in oral health. Although we know that cueing events such as having a cancer diagnosis may create a 'teachable moment' stimulating positive changes in health behaviour, we do not know whether delivering an opportunistic intervention in urgent dental care is feasible and acceptable to patients. METHODS: The feasibility study aimed to recruit 60 patients in a Dental Hospital and dental practices delivering urgent care within and outside working hours. Follow-up was by telephone, e mail and post over 4 months. RESULTS: Although the recruitment window was shortened because of COVID-19, of 47 patients assessed for eligibility, 28 were enrolled (70.1% of screened patients provided consent). A relatively high proportion were from disadvantaged backgrounds (46.4%, 13/28 receiving State benefits). Retention was 82.1% (23/28), which was also the rate of completion of the Oral Health Impact Profile co-primary outcome. The other primary outcome involved linking participant details at recruitment, with centrally-held data on services provided, with 84.6% (22/26) records partly or fully successfully matched. All intervention participants received at least some of the intervention, although we identified aspects of dental nurse training which would improve intervention fidelity. CONCLUSIONS: Despite recruitment being impacted by the pandemic, when the majority of clinical trials experienced reduced rates of recruitment, we found a high recruitment and consenting rate, even though patients were approached opportunistically to be enrolled in the trial and potentially receive an intervention. Retention rates were also high even though a relatively high proportion had a low socio-economic background. Therefore, even though patients may be in pain, and had not anticipated involvement before their urgent care visit, the study indicated that this was a feasible and acceptable setting in which to position an opportunistic intervention. This has the potential to harness the potential of the 'teachable moment' in people's lives, and provide support to help address health inequalities. TRIAL REGISTRATION: ISRCTN 10,853,330 07/10/2019.
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COVID-19 , Humanos , Estudios de Factibilidad , Encuestas y Cuestionarios , Atención Ambulatoria , Atención OdontológicaRESUMEN
BACKGROUND: People with disadvantaged backgrounds are less likely to visit the dentist for planned care, even though they have disproportionately poorer oral health. They are correspondingly more likely to experience dental problems and use urgent dental care, general practices and Accident and Emergency departments, which not only makes meeting their needs expensive, but, since these services often rely on prescriptions rather than addressing the clinical cause, can contribute to antimicrobial resistance. METHODS: The RETURN intervention has been developed with substantial community co-production, to be delivered opportunistically in urgent dental care settings. This brief intervention is delivered by dental nurses and involves material relevant to the 'in-group' targeted. The material includes booklets relating to barriers to planned dental visiting with corresponding short video clips featuring local people and including a modelling element. Dental nurses are trained to have supportive and non-judgemental conversations, assisting patients to set personal goals and action plans, which are reinforced in a follow-up text within a few weeks. A randomised controlled trial will be undertaken in 3 types of sites: dental practices delivering urgent care (a) within working hours, (b) out of hours, and (c) in a Dental Hospital. The trial will recruit 1180 adult urgent dental care users over 12 months, who have not visited a dentist for a planned care appointment for 2 years or more and do not have a dentist who they visit for routine care. It aims to investigate the effectiveness and cost-effectiveness of the intervention and to explore whether the intervention has different effects across the socio-economic gradient. Participants will be followed up at 6, 12 and 18 months after randomisation. Co-primary outcomes are attendance at a dental practice for planned care within 12 months and self-reported oral health-related quality of life at 12 months. DISCUSSION: This is a pragmatic trial, evaluating the effectiveness of the intervention under the usual condition in which it might be applied. Since dental practices work as independent contractors to the NHS, this brings implementation and fidelity challenges which will be explored and described in embedded qualitative work. TRIAL REGISTRATION: ISRCTN registry identifier ISRCTN84666712. Registered 12/04/2021.
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Terapia Conductista , Calidad de Vida , Adulto , Atención Ambulatoria , Análisis Costo-Beneficio , Atención Odontológica , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Promoting well-being and preventing poor mental health in young people is a major global priority. Building emotional competence (EC) skills via a mobile app may be an effective, scalable and acceptable way to do this. However, few large-scale controlled trials have examined the efficacy of mobile apps in promoting mental health in young people; none have tailored the app to individual profiles. METHOD/DESIGN: The Emotional Competence for Well-Being in Young Adults cohort multiple randomised controlled trial (cmRCT) involves a longitudinal prospective cohort to examine well-being, mental health and EC in 16-22 year olds across 12 months. Within the cohort, eligible participants are entered to either the PREVENT trial (if selected EC scores at baseline within worst-performing quartile) or to the PROMOTE trial (if selected EC scores not within worst-performing quartile). In both trials, participants are randomised (i) to continue with usual practice, repeated assessments and a self-monitoring app; (ii) to additionally receive generic cognitive-behavioural therapy self-help in app; (iii) to additionally receive personalised EC self-help in app. In total, 2142 participants aged 16 to 22 years, with no current or past history of major depression, bipolar disorder or psychosis will be recruited across UK, Germany, Spain, and Belgium. Assessments take place at baseline (pre-randomisation), 1, 3 and 12 months post-randomisation. Primary endpoint and outcome for PREVENT is level of depression symptoms on the Patient Health Questionnaire-9 at 3 months; primary endpoint and outcome for PROMOTE is emotional well-being assessed on the Warwick-Edinburgh Mental Wellbeing Scale at 3 months. Depressive symptoms, anxiety, well-being, health-related quality of life, functioning and cost-effectiveness are secondary outcomes. Compliance, adverse events and potentially mediating variables will be carefully monitored. CONCLUSIONS: The trial aims to provide a better understanding of the causal role of learning EC skills using interventions delivered via mobile phone apps with respect to promoting well-being and preventing poor mental health in young people. This knowledge will be used to develop and disseminate innovative evidence-based, feasible, and effective Mobile-health public health strategies for preventing poor mental health and promoting well-being. TRIAL REGISTRATION: ClinicalTrials.gov ( www.clinicaltrials.org ). Number of identification: NCT04148508 November 2019.
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Teléfono Celular , Aplicaciones Móviles , Adolescente , Adulto , Bélgica , Alemania , Humanos , Salud Mental , Estudios Prospectivos , Calidad de Vida , España , Adulto JovenRESUMEN
There is a critical need for new treatment approaches that can slow or prevent the progression of Alzheimer's disease (AD). Targets that act simultaneously on multiple relevant pathways could have significant therapeutic potential. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1a) phosphorylates both amyloid precursor protein (APP) and tau. Dyrk1a is upregulated in post-mortem brains of AD patients, and such elevated expression is associated with cognitive deficits. We previously demonstrated that small molecule inhibition of Dyrk1 is well-tolerated and reduces amyloid plaques and pathological forms of tau in 3xTg-AD mice if administered after formation of these pathologies. However, while insoluble forms of hyperphosphorylated tau were reduced by Dyrk1 inhibition, overt neurofibrillary tangle (NFT) pathology remained unchanged. Herein, we specifically test the hypothesis that inhibition of Dyrk1 prior to NFT formation will delay the onset of pathology. 3xTg-AD mice were treated chronically, beginning at 6 months of age, prior to NFT pathology. Mice were dosed daily for either 3 or 6 months and amyloid and tau pathology were assessed. We show that chronic Dyrk1 inhibition reduces insoluble forms of amyloid beta peptides (Aß) and hyper-phosphorylated tau long-term and that these reductions are associated with dramatic delay in the onset of both amyloid plaques and NFTs. In addition, we show that DYR219, a potent and selective small molecule Dyrk1 inhibitor, induces degradation of Dyrk1a protein, likely contributing to the efficacy of this small molecule approach in vivo. Collectively, these results suggest that therapeutic strategies targeting tau phosphorylation will show the greatest effect if administered very early in the pathogenesis of AD.
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Enfermedad de Alzheimer/enzimología , Enfermedad de Alzheimer/patología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Amiloide/metabolismo , Animales , Masculino , Ratones Transgénicos , Fosforilación/efectos de los fármacos , Complejo de la Endopetidasa Proteasomal/metabolismo , Inhibidores de Proteínas Quinasas/farmacocinética , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Proteolisis/efectos de los fármacos , Proteínas tau/metabolismo , Quinasas DyrKRESUMEN
BACKGROUND: In trials incorporating a health economic evaluation component, reliable validated measures for health-related quality of life (HRQOL) are essential. The EQ-5D is the preferred measure for cost-effectiveness analysis in UK trials. This paper presents a qualitative evaluation of the use of the EQ-5D-3L in a feasibility randomised control trial with participants who had a mild- to moderate learning disability and type 2 diabetes. METHODS: Researchers administered the EQ-5D-3L to 82 participants at baseline and 77 at follow-up. After each interview, researchers rated the ease of administering the EQ-5D-3L and made free-text entries on the administration experience. For a subset of 16 interviews, researchers audio-recorded more detailed journal entries. Ease of administration data were analysed using descriptive statistics. Free-text responses were subject to a basic content analysis. The EQ-5D-3L-related journal entries were transcribed, coded and analysed thematically. RESULTS: Over half of participants were perceived to experience difficulty answering some or all of the items in the EQ-5D-3L (60% at baseline; 54% at follow-up). Analysis of the free-text entries and audio journals identified four themes that question the use of the EQ-5D-3L in this population. The first theme is related to observations of participant intellectual ability and difficulties, for example, in understanding the wording of the measure. Theme 2 is related to the normalisation of adjustments for impairments, which rendered the measure less sensitive in this population. Theme 3 is related to researcher adaptation and non-standard administration. An overarching fourth theme was identified in that people with learning disabilities were viewed as 'unreliable witnesses' by both researchers and supporters. CONCLUSIONS: It is recommended that the EQ-5D-3L should not be used in isolation to assess health-related quality of life outcomes in trials research in adults with a learning disability. Further research is required to develop and evaluate a version of the EQ-5D appropriate for this population in trials research. It is unrealistic to expect that adjustments to the wording alone will deliver an appropriate measure: supporter or researcher involvement will almost always be required. This requirement needs to be factored into the development and administration guidelines of any new version of the EQ-5D for adults with a learning disability. TRIAL REGISTRATION: Current Controlled Trials ISRCTN41897033 [registered 21 January 2013].
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AIM: Anastomotic leak (AL) is a major complication of rectal cancer surgery. Despite advances in surgical practice, the rates of AL have remained static, at around 10-15%. The aetiology of AL is multifactorial, but one of the most crucial risk factors, which is mostly under the control of the surgeon, is blood supply to the anastomosis. The MRC/NIHR IntAct study will determine whether assessment of anastomotic perfusion using a fluorescent dye (indocyanine green) and near-infrared laparoscopy can minimize the rate of AL leak compared with conventional white-light laparoscopy. Two mechanistic sub-studies will explore the role of the rectal microbiome in AL and the predictive value of CT angiography/perfusion studies. METHOD: IntAct is a prospective, unblinded, parallel-group, multicentre, European, randomized controlled trial comparing surgery with intra-operative fluorescence angiography (IFA) against standard care (surgery with no IFA). The primary end-point is rate of clinical AL at 90 days following surgery. Secondary end-points include all AL (clinical and radiological), change in planned anastomosis, complications and re-interventions, use of stoma, cost-effectiveness of the intervention and quality of life. Patients should have a diagnosis of adenocarcinoma of the rectum suitable for potentially curative surgery by anterior resection. Over 3 years, 880 patients from 25 European centres will be recruited and followed up for 90 days. DISCUSSION: IntAct will rigorously evaluate the use of IFA in rectal cancer surgery and explore the role of the microbiome in AL and the predictive value of preoperative CT angiography/perfusion scanning.
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Adenocarcinoma/cirugía , Fuga Anastomótica/etiología , Fuga Anastomótica/prevención & control , Angiografía con Fluoresceína , Neoplasias del Recto/cirugía , Recto/irrigación sanguínea , Anastomosis Quirúrgica/efectos adversos , Angiografía por Tomografía Computarizada , Microbioma Gastrointestinal , Humanos , Periodo Intraoperatorio , Valor Predictivo de las Pruebas , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Recto/microbiología , Recto/cirugíaRESUMEN
The specific consequences of hyperglycaemia on placental metabolism and function are incompletely understood but likely contribute to poor pregnancy outcomes associated with diabetes mellitus (DM). This study aimed to identify the functional biochemical pathways perturbed by placental exposure to high glucose levels through integrative analysis of the trophoblast transcriptome and metabolome. The human trophoblast cell line, BeWo, was cultured in 5 or 25 mM glucose, as a model of the placenta in DM. Transcriptomic analysis using microarrays, demonstrated 5632 differentially expressed gene transcripts (≥± 1.3 fold change (FC)) following exposure to high glucose. These genes were used to generate interactome models of transcript response using BioGRID (non-inferred network: 2500 nodes (genes) and 10541 protein-protein interactions). Ultra performance-liquid chromatography-mass spectrometry (MS) and gas chromatography-MS analysis of intracellular extracts and culture medium were used to assess the response of metabolite profiles to high glucose concentration. The interactions of altered genes and metabolites were assessed using the MetScape interactome database, resulting in an integrated model of systemic transcriptome (2969 genes) and metabolome (41 metabolites) response within placental cells exposed to high glucose. The functional pathways which demonstrated significant change in response to high glucose included fatty acid ß-oxidation, phospholipid metabolism and phosphatidylinositol phosphate signalling.
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Glucosa/metabolismo , Hiperglucemia/metabolismo , Metaboloma , Placenta/metabolismo , Transcriptoma , Animales , Línea Celular , Complicaciones de la Diabetes/genética , Complicaciones de la Diabetes/metabolismo , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Femenino , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Hiperglucemia/genética , Metabolismo de los Lípidos , Ratones , Embarazo , Complicaciones del Embarazo/genética , Complicaciones del Embarazo/metabolismo , Trofoblastos/metabolismoRESUMEN
AIMS: To undertake a feasibility randomized controlled trial of supported self-management vs treatment as usual in a population of adults with obesity, Type 2 diabetes and an intellectual disability. METHODS: We conducted an individually randomized feasibility trial. Participants were adults aged >18 years with a mild or moderate intellectual disability, living in the community with Type 2 diabetes, on any therapy other than insulin. Participants had mental capacity to consent to research and the intervention. Inclusion criteria included HbA1c > 48 mmol/mol (6.5%), BMI >25 kg/m2 , or self-reported physical activity below national guideline levels. The experimental intervention was standardized supported self-management delivered by diabetes specialist nurses plus treatment as usual, compared with treatment as usual alone. Feasibility outcomes included: recruitment and retention; intervention acceptability and feasibility; data collection and completeness for physiological state and values for candidate primary outcomes (HbA1c and BMI). RESULTS: A total of 82 participants (89% of those contacted and eligible) were randomized. All supported self-management sessions were completed by 35/41 participants (85%); only four completed no sessions. Data on the follow-up candidate primary outcomes HbA1c and BMI were obtained for 75/82 (91%) and 77/82 participants (94%), respectively. The mean baseline HbA1c was 56±16.5 mmol/mol (7.3±1.5%) and the mean BMI was 34±7.6 kg/m2 . CONCLUSIONS: Adherence to supported self-management and willingness to have blood taken for outcome measurement was good. A definitive randomized controlled trial is feasible in this population. (Trial registration: Current Controlled Trials ISRCTN41897033).
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Diabetes Mellitus Tipo 2/enfermería , Discapacidad Intelectual/complicaciones , Obesidad/complicaciones , Automanejo/métodos , Afecto , Presión Sanguínea/fisiología , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/psicología , Estudios de Factibilidad , Femenino , Hemoglobina Glucada/metabolismo , Visita Domiciliaria/estadística & datos numéricos , Humanos , Discapacidad Intelectual/enfermería , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Obesidad/enfermería , Apoyo Social , Encuestas y CuestionariosRESUMEN
BACKGROUND: A recent large United Kingdom (UK) clinical trial demonstrated that positron-emission tomography-computed tomography (PET-CT)-guided administration of neck dissection (ND) in patients with advanced head and neck cancer after primary chemo-radiotherapy treatment produces similar survival outcomes to planned ND (standard care) and is cost-effective over a short-term horizon. Further assessment of long-term outcomes is required to inform a robust adoption decision. Here we present results of a lifetime cost-effectiveness analysis of PET-CT-guided management from a UK secondary care perspective. METHODS: Initial 6-month cost and health outcomes were derived from trial data; subsequent incidence of recurrence and mortality was simulated using a de novo Markov model. Health benefit was measured in quality-adjusted life years (QALYs) and costs reported in 2015 British pounds. Model parameters were derived from trial data and published literature. Sensitivity analyses were conducted to assess the impact of uncertainty and broader National Health Service (NHS) and personal social services (PSS) costs on the results. RESULTS: PET-CT management produced an average per-person lifetime cost saving of £1485 and an additional 0.13 QALYs. At a £20,000 willingness-to-pay per additional QALY threshold, there was a 75% probability that PET-CT was cost-effective, and the results remained cost-effective over the majority of sensitivity analyses. When adopting a broader NHS and PSS perspective, PET-CT management produced an average saving of £700 and had an 81% probability of being cost-effective. CONCLUSIONS: This analysis indicates that PET-CT-guided management is cost-effective in the long-term and supports the case for wide-scale adoption.
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Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/economía , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/economía , Costos de la Atención en Salud , Tomografía Computarizada por Tomografía de Emisión de Positrones/economía , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/terapia , Quimioradioterapia Adyuvante/economía , Simulación por Computador , Ahorro de Costo , Análisis Costo-Beneficio , Técnicas de Apoyo para la Decisión , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/terapia , Humanos , Masculino , Cadenas de Markov , Modelos Económicos , Disección del Cuello/economía , Terapia Neoadyuvante/economía , Valor Predictivo de las Pruebas , Años de Vida Ajustados por Calidad de Vida , Atención Secundaria de Salud/economía , Carcinoma de Células Escamosas de Cabeza y Cuello , Medicina Estatal/economía , Factores de Tiempo , Resultado del Tratamiento , Reino UnidoRESUMEN
Dyslexia is a specific impairment in learning to read and has strong heritability. An intronic deletion within the DCDC2 gene, with ~8% frequency in European populations, is increasingly used as a marker for dyslexia in neuroimaging and behavioral studies. At a mechanistic level, this deletion has been proposed to influence sensory processing capacity, and in particular sensitivity to visual coherent motion. Our re-assessment of the literature, however, did not reveal strong support for a role of this specific deletion in dyslexia. We also analyzed data from five distinct cohorts, enriched for individuals with dyslexia, and did not identify any signal indicative of associations for the DCDC2 deletion with reading-related measures, including in a combined sample analysis (N=526). We believe we conducted the first replication analysis for a proposed deletion effect on visual motion perception and found no association (N=445 siblings). We also report that the DCDC2 deletion has a frequency of 37.6% in a cohort representative of the general population recruited in Hong Kong (N=220). This figure, together with a lack of association between the deletion and reading abilities in this cohort, indicates the low likelihood of a direct deletion effect on reading skills. Therefore, on the basis of multiple strands of evidence, we conclude that the DCDC2 deletion is not a strong risk factor for dyslexia. Our analyses and literature re-evaluation are important for interpreting current developments within multidisciplinary studies of dyslexia and, more generally, contribute to current discussions about the importance of reproducibility in science.
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Dislexia/genética , Proteínas Asociadas a Microtúbulos/genética , Adolescente , Adulto , Niño , Femenino , Eliminación de Gen , Predisposición Genética a la Enfermedad , Humanos , Masculino , Percepción de Movimiento , Factores de Riesgo , Adulto JovenRESUMEN
Objectives: In the UK, patients who require intravenous antimicrobial (IVA) treatment may receive this in the community through outpatient parenteral antimicrobial therapy (OPAT) services. Services include: IVA administration at a hospital outpatient clinic (HO); IVA administration at home by a general nurse (GN) or a specialist nurse (SN); or patient self-administered (SA) IVA administration following training. There is uncertainty regarding which OPAT services represent value for money; this study aimed to estimate their cost-effectiveness. Methods: A cost-effectiveness decision-analytic model was developed using a simulation technique utilizing data from hospital records and a systematic review of the literature. The model estimates cost per QALY gained from the National Health Service (NHS) perspective for short- and long-term treatment of infections and service combinations across these. Results: In short-term treatments, HO was estimated as the most effective (0.7239 QALYs), but at the highest cost (£973). SN was the least costly (£710), producing 0.7228 QALYs. The combination between SN and HO was estimated to produce 0.7235 QALYs at a cost of £841. For long-term treatments, SN was the most effective (0.677 QALYs), costing £2379, while SA was the least costly at £1883, producing 0.666 QALYs. A combination of SA and SN was estimated to produce 0.672 QALYs at a cost of £2128. Conclusions: SN and SA are cost-effective for short- and long-term treatment of infections, while combining services may represent the second-best alternative for OPAT in the UK.
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Administración Intravenosa/estadística & datos numéricos , Atención Ambulatoria/economía , Antibacterianos/administración & dosificación , Enfermedades Transmisibles/tratamiento farmacológico , Análisis Costo-Beneficio , Utilización de Medicamentos/economía , Administración Intravenosa/economía , Antibacterianos/economía , Humanos , Modelos Estadísticos , Reino UnidoRESUMEN
BACKGROUND: Simvastatin therapy for patients with acute respiratory distress syndrome (ARDS) has been shown to be safe and associated with minimal adverse effects, but it does not improve clinical outcomes. The aim of this research was to report on mortality and cost-effectiveness of simvastatin in patients with ARDS at 12 months. METHODS: This was a cost-utility analysis alongside a multicentre, double-blind, randomised controlled trial carried out in the UK and Ireland. Five hundred and forty intubated and mechanically ventilated patients with ARDS were randomly assigned (1:1) to receive once-daily simvastatin (at a dose of 80 mg) or identical placebo tablets enterally for up to 28 days. RESULTS: Mortality was lower in the simvastatin group (31.8%, 95% confidence interval (CI) 26.1-37.5) compared to the placebo group (37.3%, 95% CI 31.6-43.0) at 12 months, although this was not significant. Simvastatin was associated with statistically significant quality-adjusted life year (QALY) gain (incremental QALYs 0.064, 95% CI 0.002-0.127) compared to placebo. Simvastatin was also less costly (incremental total costs -£3601, 95% CI -8061 to 859). At a willingness-to-pay threshold of £20,000 per QALY, the probability of simvastatin being cost-effective was 99%. Sensitivity analyses indicated that the results were robust to changes in methodological assumptions with the probability of cost-effectiveness never dropping below 90%. CONCLUSION: Simvastatin was found to be cost-effective for the treatment of ARDS, being associated with both a significant QALY gain and a cost saving. There was no significant reduction in mortality at 12 months, TRIAL REGISTRATION: ISRCTN, 88244364. Registered 26 November 2010.
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Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Simvastatina/efectos adversos , Tiempo , Adulto , Anciano , Análisis Costo-Beneficio , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Años de Vida Ajustados por Calidad de Vida , Síndrome de Dificultad Respiratoria/economía , Simvastatina/economía , Simvastatina/uso terapéutico , Medicina Estatal/estadística & datos numéricosRESUMEN
There is a growing body of literature that suggests that long-term memory (LTM) and short-term memory (STM) structures that were once thought to be distinct are actually co-dependent, and that LTM can aid retrieval from STM. The mechanism behind this effect is commonly argued to act on item memory but not on order memory. The aim of the current study was to examine whether LTM could exert an influence on STM for order by examining an effect attributed to LTM, the phonological neighbourhood effect, in a task that reduced the requirement to retain item information. In Experiment 1, 18 participants completed a serial reconstruction task where neighbourhood density alternated within the lists. In Experiment 2, 22 participants completed a serial reconstruction task using pure lists of dense and sparse neighbourhood words. In Experiment 3, 22 participants completed a reconstruction task with both mixed and pure lists. There was a significant effect of neighbourhood density with better recall for dense than sparse neighbourhood words in pure lists but not in mixed lists. Results suggest that LTM exerts an influence prior to that proposed by many models of memory for order.
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Memoria a Corto Plazo/fisiología , Aprendizaje Seriado/fisiología , Aprendizaje Verbal/fisiología , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , VocabularioRESUMEN
STUDY DESIGN: Review study. OBJECTIVES: The identification of prognostic biomarkers of spinal cord injury (SCI) will help to assign SCI patients to the correct treatment and rehabilitation regimes. Further, the detection of biomarkers that predict permanent neurological outcome would aid in appropriate recruitment of patients into clinical trials. The objective of this review is to evaluate the current state-of-play in this developing field. SETTING: Studies from multiple countries were included. METHODS: We have completed a comprehensive review of studies that have investigated prognostic biomarkers in either the blood or cerebrospinal fluid (CSF) of animals and humans following SCI. RESULTS: Targeted and unbiased approaches have identified several prognostic biomarkers in CSF and blood. These proteins associate with cellular damage following SCI and include components from neurons, oligodendrocytes and reactive astrocytes, that is, neurofilament proteins, glial fibrillary acidic protein, Tau and S100 calcium-binding protein ß. Unbiased approaches have also identified microRNAs that are specific to SCI, as well as other cell damage-associated proteins. CONCLUSIONS: The discovery and validation of stable, specific, sensitive and reproducible biomarkers of SCI is a rapidly expanding field of research. So far, few studies have utilised unbiased approaches aimed at the discovery of biomarkers within the CSF or blood in this field; however, some targeted approaches have been successfully used. Several studies using various animal models and some with small human patient cohorts have begun to pinpoint biomarkers in the CSF and blood with putative prognostic value. An increased sample size will be required to validate these biomarkers in the heterogeneous clinical setting.
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Mediadores de Inflamación/sangre , Mediadores de Inflamación/líquido cefalorraquídeo , Proteínas de Neurofilamentos/sangre , Proteínas de Neurofilamentos/líquido cefalorraquídeo , Traumatismos de la Médula Espinal/sangre , Traumatismos de la Médula Espinal/líquido cefalorraquídeo , Animales , Biomarcadores/sangre , Humanos , Pronóstico , Traumatismos de la Médula Espinal/diagnósticoRESUMEN
OBJECTIVE: To evaluate the clinical and cost-effectiveness of a new blended dental contract incentivising improved oral health compared with a traditional dental contract based on units of dental activity (UDAs). DESIGN: Non-randomised controlled study. SETTING: Six UK primary care dental practices, three working under a new blended dental contract; three matched practices under a traditional contract. PARTICIPANTS: 550 new adult patients. INTERVENTIONS: A new blended/incentive-driven primary care dentistry contract and service delivery model versus the traditional contract based on UDAs. MAIN OUTCOME MEASURES: Primary outcome was as follows: percentage of sites with gingival bleeding on probing. Secondary outcomes were as follows: extracted and filled teeth (%), caries (International Caries Detection and Assessment System (ICDAS)), oral health-related quality of life (Oral Health Impact Profile-14 (OHIP-14)). Incremental cost-effective ratios used OHIP-14 and quality adjusted life years (QALYs) derived from the EQ-5D-3L. RESULTS: At 24â months, 291/550 (53%) patients returned for final assessment; those lost to follow-up attended 6.46 appointments on average (SD 4.80). The primary outcome favoured patients in the blended contract group. Extractions and fillings were more frequent in this group. Blended contracts were financially attractive for the dental provider but carried a higher cost for the service commissioner. Differences in generic health-related quality of life were negligible. Positive changes over time in oral health-related quality of life in both groups were statistically significant. CONCLUSIONS: This is the first UK study to assess the clinical and cost-effectiveness of a blended contract in primary care dentistry. Although the primary outcome favoured the blended contract, the results are limited because 47% patients did not attend at 24â months. This is consistent with 39% of adults not being regular attenders and 27% only visiting their dentist when they have a problem. Promotion of appropriate attendance, especially among those with high need, necessitates being factored into recruitment strategies of future studies.
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Análisis Costo-Beneficio/economía , Atención Odontológica/economía , Salud Bucal/economía , Atención Primaria de Salud/economía , Reembolso de Incentivo/economía , Adulto , Análisis Costo-Beneficio/métodos , Atención Odontológica/métodos , Caries Dental/economía , Femenino , Gingivitis/economía , Humanos , Masculino , Persona de Mediana Edad , Atención Primaria de Salud/organización & administración , Reembolso de Incentivo/organización & administración , Medicina Estatal/economía , Medicina Estatal/organización & administración , Reino UnidoRESUMEN
INTRODUCTION: Outpatient parenteral antimicrobial therapy (OPAT) is used to treat a wide range of infections, and is common practice in countries such as the USA and Australia. In the UK, national guidelines (standards of care) for OPAT services have been developed to act as a benchmark for clinical monitoring and quality. However, the availability of OPAT services in the UK is still patchy and until quite recently was available only in specialist centres. Over time, National Health Service (NHS) Trusts have developed OPAT services in response to local needs, which has resulted in different service configurations and models of care. However, there has been no robust examination comparing the cost-effectiveness of each service type, or any systematic examination of patient preferences for services on which to base any business case decision. METHODS AND ANALYSIS: The study will use a mixed methods approach, to evaluate patient preferences for and the cost-effectiveness of OPAT service models. The study includes seven NHS Trusts located in four counties. There are five inter-related work packages: a systematic review of the published research on the safety, efficacy and cost-effectiveness of intravenous antibiotic delivery services; a qualitative study to explore existing OPAT services and perceived barriers to future development; an economic model to estimate the comparative value of four different community intravenous antibiotic services; a discrete choice experiment to assess patient preferences for services, and an expert panel to agree which service models may constitute the optimal service model(s) of community intravenous antibiotics delivery. ETHICS AND DISSEMINATION: The study has been approved by the NRES Committee, South West-Frenchay using the Proportionate Review Service (ref 13/SW/0060). The results of the study will be disseminated at national and international conferences, and in international journals.
Asunto(s)
Antibacterianos/administración & dosificación , Servicios de Salud Comunitaria/economía , Prioridad del Paciente , Administración Intravenosa , Atención Ambulatoria/economía , Australia , Análisis Costo-Beneficio , Servicios de Atención de Salud a Domicilio/economía , Atención Domiciliaria de Salud/economía , Humanos , Modelos Económicos , Investigación Cualitativa , Autoadministración/economía , Revisiones Sistemáticas como Asunto , Reino UnidoRESUMEN
BACKGROUND: The rising financial burden of cancer on health-care systems worldwide has led to the increased demand for evidence-based research on which to base reimbursement decisions. Economic evaluations are an integral component of this necessary research. Ascertainment of reliable health-care cost and quality-of-life estimates to inform such studies has historically been challenging, but recent advances in informatics in the United Kingdom provide new opportunities. METHODS: The costs of hospital care for breast, colorectal and prostate cancer disease-free survivors were calculated over 15 months from initial diagnosis of cancer using routinely collected data within a UK National Health Service (NHS) Hospital Trust. Costs were linked at patient level to patient-reported outcomes and registry-derived sociodemographic factors. Predictors of cost and the relationship between costs and patient-reported utility were examined. RESULTS: The study population included 223 breast cancer patients, 145 colorectal and 104 prostate cancer patients. The mean 15-month cumulative health-care costs were £12 595 (95% CI £11 517-£13 722), £12 643 (£11 282-£14 102) and £3722 (£3263-£4208), per-patient respectively. The majority of costs occurred within the first 6 months from diagnosis. Clinical stage was the most important predictor of costs for all cancer types. EQ-5D score was predictive of costs in colorectal cancer but not in breast or prostate cancer. CONCLUSION: It is now possible to evaluate health-care cost using routine NHS data sets. Such methods can be utilised in future retrospective and prospective studies to efficiently collect economic data.
Asunto(s)
Neoplasias de la Mama/economía , Neoplasias de la Mama/terapia , Neoplasias Colorrectales/economía , Neoplasias Colorrectales/terapia , Neoplasias de la Próstata/economía , Neoplasias de la Próstata/terapia , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/mortalidad , Neoplasias Colorrectales/mortalidad , Bases de Datos Factuales , Femenino , Estado de Salud , Costos de Hospital , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/metabolismo , Análisis de Supervivencia , Reino Unido , Adulto JovenRESUMEN
OBJECTIVE: The aim of this study was to assess the cost effectiveness of silicone and alginate impressions for complete dentures. METHODS: Cost effectiveness analyses were undertaken alongside a UK single centre, double blind, controlled, crossover clinical trial. Taking the perspective of the healthcare sector, effectiveness is measured using the EuroQol (EQ-5D-3L) which provides a single index value for health status that may be combined with time to produce quality adjusted life years (QALYs); and Oral Health Impact Profile (OHIP-EDENT). Incremental cost effectiveness ratios are presented representing the additional cost per one unit gained. RESULTS: Mean cost was higher in the silicone impression group (£388.57 vs. £363.18). Negligible between-group differences were observed in QALY gains; the silicone group had greater mean OHIP-EDENT gains. The additional cost using silicone was £3.41 per change of one point in the OHIP-EDENT. CONCLUSIONS: The silicone group was more costly, driven by the cost of materials. Changes in the EQ-5D and QALY gains over time and between arms were not statistically significant. Change in OHIP-EDENT score showed greater improvement in the silicone group and the difference between arms was statistically significant. Given negligible QALY gains and low level of resource use, results must be treated with caution. It is difficult to make robust claims about the comparative cost-effectiveness. CLINICAL SIGNIFICANCE: Silicone impressions for complete dentures improve patients' quality of life (OHIP-EDENT score). The extra cost of silicone impressions is £30 per patient. Dentists, patients and health care funders need to consider the clinical and financial value of silicone impressions. Different patients, different dentists, different health funders will have individual perceptions and judgements. ISRCTN01528038. NIHR-RfPB grant PB-PG-0408-16300. This article forms part of a project for which the author (TPH) won the Senior Clinical Unilever Hatton Award of the International Assocation for Dental Research, Capetown, South Africa, June 2014.
Asunto(s)
Alginatos/economía , Materiales de Impresión Dental/economía , Diseño de Dentadura/economía , Dentadura Completa/economía , Elastómeros de Silicona/economía , Adulto , Anciano , Anciano de 80 o más Años , Análisis Costo-Beneficio , Estudios Cruzados , Atención Odontológica/economía , Atención Odontológica/estadística & datos numéricos , Método Doble Ciego , Costos de los Medicamentos , Femenino , Estudios de Seguimiento , Costos de la Atención en Salud , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Salud Bucal , Estudios Prospectivos , Calidad de Vida , Años de Vida Ajustados por Calidad de Vida , Odontología Estatal/economía , Factores de Tiempo , Reino UnidoRESUMEN
OBJECTIVES: There is continuing demand for non-implant prosthodontic treatment and yet there is a paucity of high quality Randomised Controlled Trial (RCT) evidence for best practice. The aim of this research was to provide evidence for best practice in prosthodontic impressions by comparing two impression materials in a double-blind, randomised, crossover, controlled, clinical trial. METHODS: Eighty-five patients were recruited, using published eligibility criteria, to the trial at Leeds Dental Institute, UK. Each patient received two sets of dentures; made using either alginate or silicone impressions. Randomisations determined the order of assessment and order of impressions. The primary outcome was patient blinded preference for unadjusted dentures. Secondary outcomes were patient preference for the adjusted dentures, rating of comfort, stability and chewing efficiency, experience of each impression, and an OHIP-EDENT questionnaire. RESULTS: Seventy-eight (91.8%) patients completed the primary assessment. 53(67.9%) patients preferred dentures made from silicone impressions while 14(17.9%) preferred alginate impressions. 4(5.1%) patients found both dentures equally satisfactory and 7 (9.0%) found both equally unsatisfactory. There was a 50% difference in preference rates (in favour of silicone) (95%CI 32.7-67.3%, p<0.0001). CONCLUSION: There is significant evidence that dentures made from silicone impressions were preferred by patients. CLINICAL SIGNIFICANCE: Given the strength of the clinical findings within this paper, dentists should consider choosing silicone rather than alginate as their material of choice for secondary impressions for complete dentures. TRIAL REGISTRATION: ISRCTN 01528038. This article forms part of a project for which the author (TPH) won the Senior Clinical Unilever Hatton Award of the International Assocation for Dental Research, Capetown, South Africa, June 2014.
Asunto(s)
Materiales de Impresión Dental/química , Diseño de Dentadura , Dentadura Completa , Adaptación Fisiológica/fisiología , Anciano , Alginatos/química , Estudios Cruzados , Técnica de Impresión Dental , Retención de Dentadura , Método Doble Ciego , Femenino , Estudios de Seguimiento , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Humanos , Masculino , Masticación/fisiología , Persona de Mediana Edad , Salud Bucal , Prioridad del Paciente , Satisfacción del Paciente , Calidad de Vida , Elastómeros de Silicona/químicaRESUMEN
As providers of health care, we face increasing demand on our limited, indeed diminishing, resources. Economic appraisal of our interventions means assessing the trade-off between effectiveness, efficiency and equity. When rationing becomes inevitable, calculation of utility values is a valuable decision-making tool. This paper reviews objective measures of patient benefit, such as quality of life, and focuses on their application within otolaryngology.