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There is widespread interest in reaching the practical efficiency of cadmium telluride (CdTe) thin-film solar cells, which suffer from open-circuit voltage loss due to high surface recombination velocity and Schottky barrier at the back contact. Here, we focus on back contacts in the superstrate configuration with the goal of finding new materials that can provide improved passivation, electron reflection, and hole transport properties compared to the commonly used material, ZnTe. We performed a computational search among 229 binary and ternary tetrahedrally bonded structures using first-principles methods and transport models to evaluate critical material design criteria, including phase stability, electronic structure, hole transport, band alignments, and p-type dopability. Through this search, we have identified several candidate materials and their alloys (AlAs, AgAlTe2, ZnGeP2, ZnSiAs2, and CuAlTe2) that exhibit promising properties for back contacts. We hope that these new material recommendations and associated guidelines will inspire new directions in hole transport layer design for CdTe solar cells.
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STUDY QUESTION: Does natural variation exist in the endometrial stem/progenitor cell and protein composition of menstrual fluid across menstrual cycles in women? SUMMARY ANSWER: Limited variation exists in the percentage of some endometrial stem/progenitor cell types and abundance of selected proteins in menstrual fluid within and between a cohort of women. WHAT IS KNOWN ALREADY: Menstrual fluid is a readily available biofluid that can represent the endometrial environment, containing endometrial stem/progenitor cells and protein factors. It is unknown whether there is natural variation in the cellular and protein content across menstrual cycles of individual women, which has significant implications for the use of menstrual fluid in research and clinical applications. STUDY DESIGN, SIZE, DURATION: Menstrual fluid was collected from 11 non-pregnant females with regular menstrual cycles. Participants had not used hormonal medications in the previous 3 months. Participants collected menstrual fluid samples from up to five cycles using a silicone menstrual cup worn on Day 2 of menstrual bleeding. PARTICIPANTS/MATERIALS, SETTING, METHODS: Menstrual fluid samples were centrifuged to separate soluble proteins and cells. Cells were depleted of red blood cells and CD45+ leucocytes. Menstrual fluid-derived endometrial stem/progenitor cells were characterized using multicolour flow cytometry including markers for endometrial stem/progenitor cells N-cadherin (NCAD) and stage-specific embryonic antigen-1 (SSEA-1) (for endometrial epithelial progenitor cells; eEPC), and sushi domain containing-2 (SUSD2) (for endometrial mesenchymal stem cells; eMSC). The clonogenicity of menstrual fluid-derived endometrial cells was assessed using colony forming unit assays. Menstrual fluid supernatant was analyzed using a custom magnetic Luminex assay. MAIN RESULTS AND THE ROLE OF CHANCE: Endometrial stem/progenitor cells are shed in menstrual fluid and demonstrate clonogenic properties. The intraparticipant agreement for SUSD2+ menstrual fluid-derived eMSC (MF-eMSC), SSEA-1+ and NCAD+SSEA-1+ MF-eEPC, and stromal clonogenicity were moderate-good (intraclass correlation; ICC: 0.75, 0.56, 0.54 and 0.52, respectively), indicating limited variability across menstrual cycles. Endometrial inflammatory and repair proteins were detectable in menstrual fluid supernatant, with five of eight (63%) factors demonstrating moderate intraparticipant agreement (secretory leukocyte protein inhibitor (SLPI), lipocalin-2 (NGAL), lactoferrin, follistatin-like 1 (FSTL1), human epididymis protein-4 (HE4); ICC ranges: 0.57-0.69). Interparticipant variation was limited for healthy participants, with the exception of key outliers of which some had self-reported menstrual pathologies. LARGE SCALE DATA: N/A. There are no OMICS or other data sets relevant to this study. LIMITATIONS, REASONS FOR CAUTION: The main limitations to this research relate to the difficulty of obtaining menstrual fluid samples across multiple menstrual cycles in a consistent manner. Several participants could only donate across <3 cycles and the duration of wearing the menstrual cup varied between 4 and 6 h within and between women. Due to the limited sample size used in this study, wider studies involving multiple consecutive menstrual cycles and a larger cohort of women will be required to fully determine the normal range of endometrial stem/progenitor cell and supernatant protein content of menstrual fluid. Possibility for selection bias and true representation of the population of women should also be considered. WIDER IMPLICATIONS OF THE FINDINGS: Menstrual fluid is a reliable source of endometrial stem/progenitor cells and related endometrial proteins with diagnostic potential. The present study indicates that a single menstrual sample may be sufficient in characterizing a variety of cellular and protein parameters across women's menstrual cycles. The results also demonstrate the potential of menstrual fluid for identifying endometrial and menstrual abnormalities in both research and clinical settings as a non-invasive method for assessing endometrial health. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the Australian National Health and Medical Research Council to C.E.G. (Senior Research Fellowship 1024298 and Investigator Fellowship 1173882) and to J.E. (project grant 1047756), the Monash IVF Research Foundation to C.E.G. and the Victorian Government's Operational Infrastructure Support Program. K.A.W., M.L.D.-T., S.G.S. and J.E. declare no conflicts of interest. C.E.G. reports grants from NHMRC, during the conduct of the study; grants from EndoFound USA, grants from Ferring Research Innovation, grants from United States Department of Defence, grants from Clue-Utopia Research Foundation, outside the submitted work. CEF reports grants from EndoFound USA, grants from Clue-Utopia Research Foundation, outside the submitted work.
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Endometrio , Ciclo Menstrual , Células Madre , Australia , Femenino , Humanos , MenstruaciónRESUMEN
OBJECTIVE: To examine the effectiveness of interventions using the World Health Organization Health Promoting Schools (HPSs) framework approach in increasing physical activity (PA) and improving the diet of 11-18-year-olds. STUDY DESIGN: A systematic review guided by the National Health Services Centre for Reviews and Dissemination framework and reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses. METHODS: Nine databases and trial registries were searched from 2013 to 2018 for cluster randomised controlled trials involving adolescents' aged 11-18 years. We also included relevant studies from a 2014 Cochrane Review of HPS approach on health behaviours. Data were extracted from included studies and assessed for quality. RESULTS: Twelve eligible studies were identified from seven countries. The studies varied in outcome measures, sample size, quality and duration of intervention and follow-up. Only four of the included studies were of high to moderate quality. We found some evidence of effectiveness for physical activity only interventions and limited evidence of effectiveness for nutrition only and combined PA and nutrition interventions. CONCLUSIONS: There were no discernible patterns across the studies to suggest effective mechanisms for the HPS approach. The family/community component was poorly developed and superficially reported in all studies. Future research should seek to understand how best to work in partnership with secondary schools, to foster and sustain a healthy eating and physical activity culture, which aligns with their core aims. More attention should be paid to the restriction of unhealthy foods in the school environment.
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Dieta , Ejercicio Físico , Promoción de la Salud , Servicios de Salud Escolar , Instituciones Académicas , Adolescente , Niño , Dieta Saludable , Conductas Relacionadas con la Salud , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudiantes , Organización Mundial de la SaludRESUMEN
A general problem for semiconductor applications is that very slow deposition on expensive single-crystal substrates yields high crystalline quality with excellent electro-optical properties, but at prohibitive costs and throughput for many applications. In contrast, rapid deposition on inexpensive substrates or nanocrystalline films yields low costs, but comparatively inferior crystallinity, carrier transport, and recombination. Here, we present methods to deposit single-crystal material at rates 2-3 orders of magnitude faster than state-of-the-art epitaxy with low-cost methods without compromising crystalline or electro-optical quality. For example, single-crystal CdTe and CdZnTe films that would take several days to grow by molecular-beam epitaxy are deposited in 8 minutes by close-spaced sublimation, yet retain the same crystalline quality measured by X-ray diffraction rocking curves. The fast deposition is coupled with effective n- and p-type in-situ doping by In, P, and As. The epitaxy can be extended to nanocrystalline substrates. For example, we recrystallize thin CdTe films on glass to deposit large grains with low defect density. The results provide new research paths for photovoltaics, detectors, infrared imaging, flexible electronics, and other applications.
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Background: Improving Access to Psychological Therapies (IAPT) constitutes a key element of England's national mental health strategy. Accessing IAPT usually requires patients to self-refer on the advice of their GP. Little is known about how GPs perceive and communicate IAPT services with patients from low-income communities, nor how the notion of self-referral is understood and responded to by such patients.Aims: This paper examines how IAPT referrals are made by GPs and how these referrals are perceived and acted on by patients from low-income backgroundsMethod: Findings are drawn from in-depth interviews with low-income patients experiencing mental distress (n = 80); interviews with GPs (n = 10); secondary analysis of video-recorded GP-patient consultations for mental health (n = 26).Results: GPs generally supported self-referral, perceiving it an important initial step towards patient recovery. Most patients however, perceived self-referral as an obstacle to accessing IAPT, and felt their mental health needs were being undermined. The way that IAPT was discussed and the pathway for referral appears to affect uptake of these services.Conclusions: A number of factors deter low-income patients from self-referring for IAPT. Understanding these issues is necessary in enabling the development of more effective referral and support mechanisms within primary care.
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Trastornos Mentales , Servicios de Salud Mental , Accesibilidad a los Servicios de Salud , Humanos , Trastornos Mentales/terapia , Atención Primaria de Salud , Derivación y ConsultaRESUMEN
BACKGROUND: The ability to predict defibrillation efficacy at the time of subcutaneous implantable cardioverter-defibrillator implantation without the need to induce ventricular fibrillation might eliminate the need for defibrillation testing. The purpose of this study was to determine the association of high-voltage impedance and system implant position on ventricular fibrillation conversion success with a submaximal 65-J shock. METHODS: In the subcutaneous implantable cardioverter-defibrillator IDE study (Investigational Device Exemption), a successful conversion test required 2 consecutive ventricular fibrillation conversions at 65 J in either shock vector. Chest radiographs were obtained after implantation. Patients with imaging and impedance data were included. Suboptimal device position was defined as an inferior electrode or pulse generator or electrode coil depth >3 mm anterior to the sternum. Absence of suboptimal positional parameters was defined as appropriate position. Conversion success rate was calculated among all 65-J tests. RESULTS: Of 314 patients who underwent subcutaneous implantable cardioverter-defibrillator implantation, 282 patients were included in this analysis. There were 637 inductions to test defibrillation at 65 J. Sixty-two conversion failures (9.7%) occurred in 42 (14.9%) patients. Lower body mass index and lower shock impedance were associated with higher conversion success rate, whereas white race was associated with lower conversion success rate. Suboptimal position was more common in obese patients. Inferior electrode and greater distance between the lead and sternum were associated with a higher impedance. When appropriate system position was achieved, conversion failure was not associated with high body mass index. CONCLUSIONS: Subcutaneous implantable cardioverter-defibrillator shock efficacy is associated with system position and high-voltage system impedance. A high impedance is associated with inferiorly placed pulse generator and electrode system, inadequate coil depth, and a lower rate of defibrillator success. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01064076.
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Desfibriladores Implantables , Fibrilación Ventricular/prevención & control , Adulto , Anciano , Índice de Masa Corporal , Impedancia Eléctrica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiografía Torácica , Fibrilación Ventricular/fisiopatologíaRESUMEN
Interfaces at the front of superstrate CdTe-based solar cells are critical to carrier transport, recombination, and device performance, yet determination of the chemical structure of these nanoscale regions has remained elusive. This is partly due to changes that occur at the front interfaces during high temperature growth and substantive changes occurring during postdeposition processing. In addition, these buried interfaces are extremely difficult to access in a way that preserves chemical information. In this work, we use a recently developed thermomechanical cleaving technique paired with X-ray photoelectron spectroscopy to probe oxidation states at the SnO2 interface of CdTe solar cells. We show that the tin oxide front electrode promotes the formation of nanometer-scale oxides of tellurium and sulfur. Most oxidation occurs during CdCl2/O2 activation. Surprisingly, we show that relatively low-temperature anneals (180-260 °C) used to diffuse and activate copper acceptors in a doping/back contact process also cause significant changes in oxidation at the front of the cell, providing a heretofore missing aspect of how back contact processes can modify device transport, recombination, and performance. Device performance is shown to correlate with the extent of tellurium and sulfur oxidation within this nanometer-scale region. Mechanisms responsible for these beneficial effects are proposed.
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Thin film materials for photovoltaics such as cadmium telluride (CdTe), copper-indium diselenide-based chalcopyrites (CIGS), and lead iodide-based perovskites offer the potential of lower solar module capital costs and improved performance to microcrystalline silicon. However, for decades understanding and controlling hole and electron concentration in these polycrystalline films has been extremely challenging and limiting. Ionic bonding between constituent atoms often leads to tenacious intrinsic compensating defect chemistries that are difficult to control. Device modeling indicates that increasing CdTe hole density while retaining carrier lifetimes of several nanoseconds can increase solar cell efficiency to 25%. This paper describes in-situ Sb, As, and P doping and post-growth annealing that increases hole density from historic 1014 limits to 1016-1017 cm-3 levels without compromising lifetime in thin polycrystalline CdTe films, which opens paths to advance solar performance and achieve costs below conventional electricity sources.
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BACKGROUND: Recruitment and retention of participants is crucial for statistical power and internal and external validity and participant engagement is essential for behaviour change. However, many school-based interventions focus on programme content rather than the building of supportive relationships with all participants and tend to employ specific standalone strategies, such as incentives, to improve retention. We believe that actively involving stakeholders in both intervention and trial design improves recruitment and retention and increases the chances of creating an effective intervention. METHODS: The Healthy Lifestyles Programme, HeLP (an obesity prevention programme for children 9-10 years old) was developed using intervention mapping and involved extensive stakeholder involvement in both the design of the trial and the intervention to ensure that: (i) delivery methods were suitably engaging, (ii) deliverers had the necessary skills and qualities to build relationships and (iii) the intervention dovetailed with the National Curriculum. HeLP was a year-long intervention consisting of 4 multi-component phases using a range of delivery methods. We recruited 1324 children from 32 schools from the South West of England to a cluster-randomised controlled trial to determine the effectiveness of HeLP in preventing obesity. The primary outcome was change in body mass index standard deviation score (BMI SDS) at 24 months post randomisation. Secondary outcomes included additional anthropometric and behavioural (physical activity and diet) measures at 18 and 24 months. RESULTS: Anthropometric and behavioural measures were taken in 99%, 96% and 94% of children at baseline, 18 and 24 months, respectively, with no differential follow up between the control and intervention groups at each time point. All children participated in the programme and 92% of children and 77% of parents across the socio-economic spectrum were considered to have actively engaged with HeLP. CONCLUSIONS: We attribute our excellent retention and engagement results to the high level of stakeholder involvement in both trial and intervention design, the building of relationships using appropriate personnel and creative delivery methods that are accessible to children and their families across the social spectrum. TRIAL REGISTRATION: International Standard Randomised Controlled Trials Register, ISRCTN15811706 . Registered on 1 May 2012.
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Familia , Estilo de Vida Saludable , Selección de Paciente , Obesidad Infantil/prevención & control , Sujetos de Investigación , Conducta de Reducción del Riesgo , Servicios de Salud Escolar/organización & administración , Participación de los Interesados , Factores de Edad , Índice de Masa Corporal , Niño , Conducta Infantil , Dieta Saludable , Inglaterra , Ejercicio Físico , Familia/psicología , Femenino , Conductas Relacionadas con la Salud , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Obesidad Infantil/diagnóstico , Obesidad Infantil/fisiopatología , Obesidad Infantil/psicología , Investigadores/psicología , Sujetos de Investigación/psicología , Factores de Riesgo , Tamaño de la Muestra , Factores Socioeconómicos , Factores de Tiempo , Resultado del Tratamiento , Pérdida de PesoRESUMEN
Sterile haemorrhagic cystitis (SHC) is a known risk of cyclophosphamide treatment. Diuresis using furosemide is effective in canines when maximally tolerated dosed cyclophosphamide is administered. This retrospective study aimed to determine whether orally administered furosemide decreased the incidence of SHC. Secondary aims were to identify predisposing factors for SHC. One-hundred and fifteen dogs treated with metronomic cyclophosphamide were analysed retrospectively. Populations were not randomized. 25 dogs (21.7%) developed SHC. Furosemide administration significantly reduced the likelihood of SHC development (P = 0.010, where SHC was diagnosed in 30.3% of dogs administered cyclophosphamide without furosemide, and 10.2% of dogs administered cyclophosphamide with furosemide). Age, gender, breed, bodyweight, number of cyclophosphamide treatments, piroxicam use and previous or pre-existing disease were not found to be associated with SHC development. This study demonstrates furosemide is effective in the prevention of SHC and its use may be considered when implementing metronomic cyclophosphamide therapy.
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Antineoplásicos Alquilantes/efectos adversos , Ciclofosfamida/efectos adversos , Cistitis/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , Furosemida/uso terapéutico , Administración Metronómica , Animales , Antineoplásicos Alquilantes/administración & dosificación , Ciclofosfamida/administración & dosificación , Cistitis/inducido químicamente , Cistitis/prevención & control , Enfermedades de los Perros/inducido químicamente , Enfermedades de los Perros/prevención & control , Perros , Femenino , Masculino , Neoplasias/tratamiento farmacológico , Neoplasias/veterinaria , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Thrombocytopenia is commonly encountered in veterinary oncology. Currently, there are no standard guidelines regarding the administration of chemotherapy to the patients with thrombocytopenia. This observational epidemiological cohort study aimed to determine whether thrombocytopenic dogs were at increased risk of gastrointestinal adverse effects (vomiting, diarrhoea, inappetence) or haemorrhage following administration of standard doses of chemotherapy. The adverse effects following 77 prospectively identified episodes of thrombocytopenia (platelet count, <200 000 µL-1 ) were compared with the adverse effects experienced in a retrospective cohort (platelet count >200 000 µL-1 ), and evaluated by statistical analysis. Overall, there was no statistically significant difference in the incidence of gastrointestinal adverse effects or haemorrhage between thrombocytopenic and control dogs. The control group of dogs with lymphoma were statistically more likely to experience vomiting as an adverse effect of chemotherapy (P = 0.028). The results presented here showed no evidence for an increased risk of gastrointestinal adverse effects or haemorrhage in thrombocytopenic dogs after receiving standard doses of chemotherapy.
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Antineoplásicos/efectos adversos , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades Gastrointestinales/veterinaria , Neoplasias/veterinaria , Trombocitopenia/veterinaria , Animales , Antineoplásicos/uso terapéutico , Estudios de Cohortes , Enfermedades de los Perros/sangre , Perros , Enfermedades Gastrointestinales/sangre , Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/etiología , Neoplasias/sangre , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Trombocitopenia/etiología , Australia Occidental/epidemiologíaRESUMEN
Using two-photon tomography, carrier lifetimes are mapped in polycrystalline CdTe photovoltaic devices. These 3D maps probe subsurface carrier dynamics that are inaccessible with traditional optical techniques. They reveal that CdCl2 treatment of CdTe solar cells suppresses nonradiative recombination and enhances carrier lifetimes throughout the film with substantial improvements particularly near subsurface grain boundaries and the critical buried p-n junction.
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BACKGROUND: Schools have long been viewed as a good setting in which to encourage healthy lifestyles amongst children, and schools in many countries aspire to more comprehensive, integrated approaches to health promotion. Recent reviews have identified evidence of the effects of school health promotion on children's and young people's health. However, understanding of how such programmes can be implemented in schools is more limited. METHODS: We conducted a realist review to identify the conditions and actions which lead to the successful implementation of health promotion programmes in schools. We used the international literature to develop programme theories which were then tested using evaluations of school health promotion programmes conducted in the United Kingdom (UK). Iterative searching and screening was conducted to identify sources and clear criteria applied for appraisal of included sources. A review advisory group comprising educational and public health practitioners, commissioners, and academics was established at the outset. RESULTS: In consultation with the review advisory group, we developed four programme theories (preparing for implementation, initial implementation, embedding into routine practice, adaptation and evolution); these were then refined using the UK evaluations in the review. This enabled us to identify transferable mechanisms and enabling and constraining contexts and investigate how the operation of mechanisms differed in different contexts. We also identified steps that should be taken at a senior level in relation to preparing for implementation (which revolved around negotiation about programme delivery) and initial implementation (which centred on facilitation, support, and reciprocity-the latter for both programme deliverers and pupils). However, the depth and rigour of evidence concerning embedding into routine practice and adaptation and evolution was limited. CONCLUSIONS: Our findings provide guidance for the design, implementation, and evaluation of health promotion in schools and identify the areas where further research is needed.
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Promoción de la Salud/organización & administración , Desarrollo de Programa/métodos , Servicios de Salud Escolar/organización & administración , Niño , Humanos , Evaluación de Programas y Proyectos de Salud , Reino UnidoRESUMEN
CASE HISTORY: A 5-year-old male neutered Poodle cross presented with a 2-week history of non-specific gastrointestinal signs including vomiting, inappetence and lethargy (Case 1). A 14-year-old male neutered Staffordshire Bull Terrier presented with a 6-week history of progressive inappetence and lethargy (Case 2). CLINICAL FINDINGS: On presentation, Case 1 was dehydrated and had repeatable cranial abdominal pain. Mild hypoproteinemia with hypoalbuminemia, and electrolyte disturbances were found on biochemistry profile. Abdominal ultrasonography showed moderate diffuse small intestinal wall irregularity and moderate local lymphadenopathy. Haematology was repeated 2 days after initial presentation and showed a marked leucocytosis associated with an elevated circulating neoplastic cell population. On presentation, Case 2 was dehydrated, had palpable hepatomegaly and a mild generalised lymphadenopathy. A low number of large, atypical lymphocytes were found on haematology. Sonographically there was hepatomegaly with diffuse parenchymal changes and severe mesenteric lymphadenopathy. LABORATORY FINDINGS: Aspirates from the abdominal lymph nodes (Cases 1 and 2) and liver (Case 2), and blood smears revealed atypical neoplastic lymphoid populations, predominantly comprising large lymphocytes. Immunocytochemistry failed to determine the lymphoid phenotype in Case 1 but supported a T cell phenotype in Case 2. Immunohistochemistry of formalin-fixed paraffin-embedded (FF-PE) blood clots was able to identify a T cell phenotype in both cases. PCR for antigen receptor rearrangement results from both cases were consistent with an expanded T cell population. DIAGNOSIS: In both cases, immunohistochemistry on FF-PE blood clots revealed a circulating T cell lymphocyte population, consistent with T cell lymphoproliferative neoplasia. CLINICAL RELEVANCE: Immunohistochemistry on FF-PE blood clots offers clinicians a reliable, inexpensive and minimally invasive method of phenotyping neoplastic cells in circulation. Compared to other available methods, prolonged sample stability allowing for transport and retrospective examination is a distinct advantage. This technique should be considered a useful adjunct to the currently available methods for the phenotypic evaluation of lymphoid leukaemia in dogs.
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Enfermedades de los Perros/diagnóstico , Inmunohistoquímica/veterinaria , Linfocitos/patología , Linfoma de Células T/veterinaria , Animales , Enfermedades de los Perros/sangre , Enfermedades de los Perros/patología , Perros , Inmunohistoquímica/métodos , Linfoma de Células T/sangre , Linfoma de Células T/diagnóstico , Linfoma de Células T/patología , MasculinoRESUMEN
OBJECTIVE: To explore areas of consensus and conflict in relation to perceived public involvement (PI) barriers and drivers, perceived impacts of PI and ways of evaluating PI approaches in health and social care research. BACKGROUND: Internationally and within the UK the recognition of potential benefits of PI in health and social care research is gathering momentum and PI is increasingly identified by organisations as a prerequisite for funding. However, there is relatively little examination of the impacts of PI and how those impacts might be measured. DESIGN: Mixed method, three-phase, modified Delphi technique, conducted as part of a larger MRC multiphase project. SAMPLE: Clinical and non-clinical academics, members of the public, research managers, commissioners and funders. FINDINGS: This study found high levels of consensus about the most important barriers and drivers to PI. There was acknowledgement that tokenism was common in relation to PI; and strong support for the view that demonstrating the impacts and value of PI was made more difficult by tokenistic practice. PI was seen as having intrinsic value; nonetheless, there was clear support for the importance of evaluating its impact. Research team cohesion and appropriate resources were considered essential to effective PI implementation. Panellists agreed that PI can be challenging, but can be facilitated by clear guidance, together with models of good practice and measurable standards. CONCLUSIONS: This study is the first to present empirical evidence of the opinions voiced by key stakeholders on areas of consensus and conflict in relation to perceived PI barriers and drivers, perceived impacts of PI and the need to evaluate PI. As such it further contributes to debate around best practice in PI, the potential for tokenism and how best to evaluate the impacts of PI. These findings have been used in the development of the Public Involvement Impact Assessment Framework (PiiAF), an online resource which offers guidance to researchers and members of the public involved in the PI process.
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Participación de la Comunidad , Atención a la Salud , Investigación , Actitud , Consenso , Técnica Delphi , Humanos , Factores SociológicosRESUMEN
OBJECTIVES: To determine the effectiveness of enzyme replacement therapy (ERT) for adults with late-onset Pompe disease. DESIGN: A longitudinal cohort study including prospective and retrospective clinical outcome data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Treated patients contributed data before and during treatment. Untreated patients contributed natural history data. PARTICIPANTS: Consenting adults (N = 62) with a diagnosis of late-onset Pompe disease who attended a specialist treatment centre in England. This cohort represented 83 % of all patients in the UK with a confirmed diagnosis of this rare condition. At study entry, all but three patients were receiving ERT (range of treatment duration, 0 to 3.1 years). OUTCOME MEASURES: Percent predicted forced vital capacity (%FVC); ventilation dependency; mobility; 6 min walk test (6MWT); muscle strength and body mass index (BMI). RESULTS: An association was found between time on ERT and significant increases in the distance walked in the 6MWT (p < 0.001) and muscle strength scores (p < 0.001). Improvements in both these measures were seen over the first 2 years of treatment with ERT. No statistically significant relationship was found between time on ERT and respiratory function or in BMI. CONCLUSIONS: These data provide some further evidence of the effectiveness of ERT in adults with late-onset Pompe disease. SYNOPSIS: The results of this longitudinal cohort study of 62 adults with late-onset Pompe disease, provide further evidence on the effectiveness of ERT in this rare condition.
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Terapia de Reemplazo Enzimático/métodos , Enfermedad del Almacenamiento de Glucógeno Tipo II/tratamiento farmacológico , Adolescente , Adulto , Edad de Inicio , Anciano , Índice de Masa Corporal , Inglaterra , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Fuerza Muscular , Estudios Prospectivos , Estudios Retrospectivos , Resultado del Tratamiento , Caminata , Adulto JovenRESUMEN
OBJECTIVES: To determine the effectiveness of enzyme replacement therapy (ERT) for adults and children with Fabry disease. DESIGN: Cohort study including prospective and retrospective clinical data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Treated patients contributed data before and during treatment and untreated patients contributed natural history data. PARTICIPANTS: Consenting adults (N = 289) and children (N = 22) with a confirmed diagnosis of Fabry disease attending a specialist Lysosomal Storage Disorder treatment centre in England. At recruitment 211 adults and seven children were on ERT (range of treatment duration, 0 to 9.7 and 0 to 4.2 years respectively). OUTCOME MEASURES: Clinical outcomes chosen to reflect disease progression included left ventricular mass index (LVMI); proteinuria; estimated glomerular filtration rate (eGFR); pain; hearing and transient ischaemic attacks (TIA)/stroke. RESULTS: We found evidence of a statistically significant association between time on ERT and a small linear decrease in LVMI (p = 0.01); a reduction in the risk of proteinuria after adjusting for angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (p < 0.001) and a small increase in eGFR in men and women without pre-treatment proteinuria (p = 0.01 and p < 0.001 respectively). The same analyses in children provided no statistically significant results. No associations between time on ERT and pain, risk of needing a hearing aid, or risk of stroke or TIAs, were found. CONCLUSIONS: These data provide some further evidence on the long-term effectiveness of ERT in adults with Fabry disease, but evidence of effectiveness could not be demonstrated in children.
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Terapia de Reemplazo Enzimático/métodos , Enfermedad de Fabry/complicaciones , Enfermedad de Fabry/tratamiento farmacológico , alfa-Galactosidasa/uso terapéutico , Adolescente , Adulto , Anciano , Niño , Preescolar , Progresión de la Enfermedad , Inglaterra , Femenino , Tasa de Filtración Glomerular , Ventrículos Cardíacos/anatomía & histología , Humanos , Lactante , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteinuria/complicaciones , Análisis de Regresión , Estudios Retrospectivos , Accidente Cerebrovascular/complicaciones , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: To determine the effectiveness of enzyme replacement therapies (ERT) for children with Gaucher disease (GD). DESIGN: A longitudinal cohort study including prospective and retrospective clinical data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Children on treatment contributed data before and during treatment. Children not on treatment contributed natural history data. PARTICIPANTS: Consenting children (N = 25, aged 1.1 to 15.6 years) with a diagnosis of GD (14 with GD1 and 11 with GD3) who attended a specialist treatment centre in England. At recruitment, 24 patients were receiving ERT (mean treatment duration, 5.57 years; range 0-13.7 years). OUTCOME MEASURES: Clinical outcomes chosen to reflect disease progression, included platelet count; haemoglobin and absence/presence of bone pain. RESULTS: Duration of ERT was associated with statistically significant improvements in platelet count (p < 0.001), haemoglobin (p < 0.001), and reported bone pain (p = 0.02). The magnitude of effect on haematological parameters was greater in children with GD3 than in those with GD1. CONCLUSIONS: These data provide further evidence of the long-term effectiveness of ERT in children with GD.
Asunto(s)
Terapia de Reemplazo Enzimático/métodos , Enfermedad de Gaucher/tratamiento farmacológico , Glucosilceramidasa/uso terapéutico , Adolescente , Niño , Preescolar , Progresión de la Enfermedad , Inglaterra , Femenino , Enfermedad de Gaucher/complicaciones , Hemoglobinas/análisis , Humanos , Lactante , Estudios Longitudinales , Masculino , Recuento de Plaquetas , Estudios Prospectivos , Análisis de Regresión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVES: To determine the effectiveness of enzyme replacement therapies (ERT) for adults with Gaucher disease (GD). DESIGN: A longitudinal, multi-centre cohort study, including prospective and retrospective clinical data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Treated patients contributed data before and during treatment. Untreated patients contributed natural history data. PARTICIPANTS: Consenting adults (N = 150, aged 16 to 83 years) with a diagnosis of GD who attended a specialist treatment centre in England. At recruitment, 131 patients were receiving ERT (mean treatment duration, 10.8 years; range 0-18 years). OUTCOME MEASURES: Clinical outcomes chosen to reflect disease progression, included platelet count; haemoglobin; absence/presence of bone pain; spleen and liver volumes and AST levels. RESULTS: One hundred and fifty adults were recruited. Duration of ERT was associated with statistically significant improvements in platelet count (p < 0.001), haemoglobin (p < 0.001), liver and spleen volumes (p < 0.001) and AST levels (p = 0.02). CONCLUSIONS: These data provide further evidence of the long-term effectiveness of ERT in adults with GD.