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OBJECTIVE: Pre-eclampsia (PE) remains a leading cause of maternal and fetal morbidity and mortality. A first-trimester screening algorithm predicting the risk of early-onset PE has been developed and validated. Early prediction coupled with initiation of aspirin at 11-13 weeks in women identified as high risk is effective at reducing the prevalence of early-onset PE. The aim of this study was to evaluate the cost-effectiveness of this first-trimester screening program coupled with early use of low-dose aspirin in women at high risk of developing early-onset PE, in comparison to current practice in Canada. METHODS: A decision analysis was performed based on a theoretical population of 387 516 live births in Canada in 1 year. The clinical and financial impact of early preventative screening using the Fetal Medicine Foundation algorithm for prediction of early-onset PE coupled with early (< 16 weeks) use of low-dose aspirin in those at high risk was simulated and compared with current practice using decision-tree analysis. The probabilities at each decision point and associated costs of utilized resources were calculated based on published literature and public databases. RESULTS: Of the theoretical 387 516 births per year, the estimated prevalence of early PE based on first-trimester screening and aspirin use was 705 vs 1801 cases based on the current practice. This was associated with an estimated total cost of C$9.52 million with the first-trimester screening program compared with C$23.91 million with current practice for the diagnosis and management of women with early-onset PE. This equals an annual cost saving to the Canadian healthcare system of approximately C$14.39 million. CONCLUSIONS: The implementation of a first-trimester screening program for PE and early intervention with aspirin in women identified as high risk for early PE has the potential to prevent a significant number of early-onset PE cases with a substantial associated cost saving to the healthcare system in Canada. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
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Aspirina/administração & dosagem , Programas de Rastreamento/economia , Inibidores da Agregação Plaquetária/administração & dosagem , Pré-Eclâmpsia/prevenção & controle , Adulto , Algoritmos , Análise Custo-Benefício , Árvores de Decisões , Feminino , Humanos , Pré-Eclâmpsia/diagnóstico por imagem , Pré-Eclâmpsia/economia , Gravidez , Primeiro Trimestre da Gravidez , Gravidez de Alto Risco , Ultrassonografia Pré-Natal/economiaRESUMO
Guidelines recommend that women take folic acid supplements in the preconception period to prevent neural tube defects (NTDs) in their offspring. Estimates of adherence to this recommendation across different countries worldwide have not been synthesized. Medline, CINAHL, and EMBASE were systematically searched to identify studies reporting the prevalence of preconception folic acid supplementation. Pooled prevalence estimates for each country (where data were available) were calculated; and differences based on demographic, methodological, and study quality characteristics were examined. Of 3372 titles and abstracts screened, 722 full-texts were reviewed and 105 articles that reported 106 estimates of preconception folic acid supplementation in 34 countries were included. Pooled prevalence estimates were 32-51% in North America, 9-78% in Europe, 21-46% in Asia, 4-34% in the Middle East, 32-39% in Australia/New Zealand, and 0% in Africa. No South American studies were identified. Higher supplementation prevalence was observed in studies that had more highly educated samples, were conducted in fertility clinics, and assessed folic acid use via self-report. Of note, only 32% and 28% of studies reported timing of folic acid use and adherence to folic acid, respectively. Preconception folic acid supplementation is highly variable worldwide and many women may not achieve sufficient folate levels to prevent NTDs. To better understand non-adherence, recommendations for future research include: more explicit reporting of methodology, more detailed assessment of folic acid use, assessment of variables potentially relevant to folic acid use, and surveillance of folic acid use in a greater diversity of countries, especially in the developing world.
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Suplementos Nutricionais , Ácido Fólico/administração & dosagem , Defeitos do Tubo Neural/prevenção & controle , Cuidado Pré-Concepcional/métodos , Ásia , Europa (Continente) , Feminino , Saúde Global , Humanos , América do Norte , Gravidez , PrevalênciaRESUMO
OBJECTIVES: To define a protocol for the first-trimester assessment of uterine artery pulsatility index (UtA-PI) using the new transverse technique, to evaluate UtA-PI measured using the transverse approach vs that obtained using the conventional sagittal approach and to determine if accelerated onsite training (in both methods) of inexperienced sonographers can achieve reproducible UtA-PI measurements comparable with those obtained by an experienced sonographer. METHODS: This was a prospective observational study of women with a singleton pregnancy attending for routine combined first-trimester screening at 11 to 13 + 6 weeks' gestation. The study consisted of two parts, each conducted at a different center (Part 1 in Calgary, Canada and Part 2 in Hong Kong). In Part 1, UtA-PI measurements were performed using the transverse and sagittal techniques by four sonographers trained in both methods, in 10 cases each, and measurement indices (PI), time required and subjective difficulty in obtaining satisfactory measurements were compared. The one sample t-test and Wilcoxon signed rank test were used when appropriate. Bland-Altman plots were used to assess measurement agreement, and intraclass correlation coefficient (ICC) was used to evaluate measurement reliability. A target plot was used to assess measures of central tendency and dispersion. In Part 2, one experienced and three inexperienced sonographers prospectively measured UtA-PI using both approaches in 42 and 35 women, respectively. Inexperienced sonographers underwent accelerated onsite training by the experienced sonographer. Measurement approach and sonographer order were on a random basis. ICC, Bland-Altman and Passing-Bablok analyses were performed to assess measurement agreement and reliability and effect of accelerated training. RESULTS: In Part 1, no difference was observed between the two techniques in mean time to acquire the measurements (118 s for sagittal vs 106 s for transverse; P = 0.38). The four sonographers reported that the transverse technique was subjectively easier to perform (P = 0.04). Bias and ICC for mean UtA-PI between sagittal and transverse measurements were -0.05 (95% limits of agreement, -0.48 to 0.37) and 0.94, respectively. Measurements obtained using the transverse technique after correcting for gestational age were significantly closer to the expected distribution than those obtained using the sagittal technique. In Part 2, there were no significant differences in median UtA-PI measured using the different approaches for both experienced and inexperienced sonographers (P > 0.05 for all sonographers). Mean UtA-PI measurement reliability between approaches was high for the experienced (ICC = 0.92) and inexperienced (ICC > 0.80) sonographers. UtA-PI measurement approaches did not deviate from linearity, while bias ranged from -0.10 to 0.07. The median time required was similar between the techniques (56.1 s for sagittal vs 49.3 s for transverse; P = 0.054). CONCLUSIONS: This novel transverse approach for the measurement of UtA-PI in the first trimester appears to be comparable with the sagittal approach in terms of reliability, reproducibility and time required, and may be easier to perform. Providing accelerated onsite training can be helpful for improving the reliability of UtA-PI measurements and could potentially facilitate the broad implementation of first-trimester pre-eclampsia screening. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
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Pré-Eclâmpsia/diagnóstico por imagem , Ultrassonografia Pré-Natal , Artéria Uterina/diagnóstico por imagem , Adulto , Velocidade do Fluxo Sanguíneo , Feminino , Humanos , Pré-Eclâmpsia/fisiopatologia , Valor Preditivo dos Testes , Gravidez , Primeiro Trimestre da Gravidez , Estudos Prospectivos , Fluxo Pulsátil , Artéria Uterina/fisiologiaRESUMO
OBJECTIVES: An obstetric comorbidity index has been developed recently with superior performance characteristics relative to general comorbidity measures in an obstetric population. This study aimed to externally validate this index and to examine the impact of including hospitalisation/delivery records only when estimating comorbidity prevalence and discriminative performance of the obstetric comorbidity index. DESIGN: Validation study. SETTING: Alberta, Canada. POPULATION: Pregnant women who delivered a live or stillborn infant in hospital (n = 5995). METHODS: Administrative databases were linked to create a population-based cohort. Comorbid conditions were identified from diagnoses for the delivery hospitalisation, all hospitalisations and all healthcare contacts (i.e. hospitalisations, emergency room visits and physician visits) that occurred during pregnancy and 3 months pre-conception. Logistic regression was used to test the discriminative performance of the comorbidity index. MAIN OUTCOME MEASURES: Maternal end-organ damage and extended length of stay for delivery. RESULTS: Although prevalence estimates for comorbid conditions were consistently lower in delivery records and hospitalisation data than in data for all healthcare contacts, the discriminative performance of the comorbidity index was constant for maternal end-organ damage [all healthcare contacts area under the receiver operating characteristic curve (AUC) = 0.70; hospitalisation data AUC = 0.67; delivery data AUC = 0.65] and extended length of stay for delivery (all healthcare contacts AUC = 0.60; hospitalisation data AUC = 0.58; delivery data AUC = 0.58). CONCLUSIONS: The obstetric comorbidity index shows similar performance characteristics in an external population and is a valid measure of comorbidity in an obstetric population. Furthermore, the discriminative performance of the comorbidity index was similar for comorbidities ascertained at the time of delivery, in hospitalisation data or through all healthcare contacts.
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Comorbidade , Parto Obstétrico/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Complicações do Trabalho de Parto/epidemiologia , Avaliação de Resultados em Cuidados de Saúde/normas , Índice de Gravidade de Doença , Adulto , Área Sob a Curva , Canadá/epidemiologia , Feminino , Hospitalização , Humanos , Modelos Logísticos , GravidezRESUMO
OBJECTIVE: Non-invasive fetal Rhesus (Rh) D genotyping, using cell-free fetal DNA (cffDNA) in the maternal blood, allows targeted antenatal anti-RhD prophylaxis in unsensitized RhD-negative pregnant women. The purpose of this study was to determine the cost and benefit of this approach as compared to routine antenatal anti-RhD prophylaxis for all unsensitized RhD-negative pregnant women, as is the current policy in the province of Alberta, Canada. METHODS: This study was a decision analysis based on a theoretical population representing the total number of pregnancies in Alberta over a 1-year period (n = 69 286). A decision tree was created that outlined targeted prophylaxis for unsensitized RhD-negative pregnant women screened for cffDNA (targeted group) vs routine prophylaxis for all unsensitized RhD-negative pregnant women (routine group). Probabilities at each decision point and costs associated with each resource were calculated from local clinical and administrative data. Outcomes measured were cost, number of women sensitized and doses of Rh immunoglobulin (RhIG) administered. RESULTS: The estimated cost per pregnancy for the routine group was 71.43 compared with 67.20 Canadian dollars in the targeted group. The sensitization rates per RhD-negative pregnancy were equal, at 0.0012, for the current and targeted programs. Implementing targeted antenatal anti-RhD prophylaxis would save 4072 doses (20.1%) of RhIG over a 1-year period in Alberta when compared to the current program. CONCLUSIONS: These data support the feasibility of a targeted antenatal anti-RhD prophylaxis program, at a lower cost than that of the existing routine prophylaxis program, with no increased risk of sensitization.
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DNA/sangue , Complicações Hematológicas na Gravidez/prevenção & controle , Isoimunização Rh/prevenção & controle , Imunoglobulina rho(D)/uso terapêutico , Adulto , Canadá , Sistema Livre de Células , Análise Custo-Benefício , Feminino , Humanos , Recém-Nascido , Gravidez , Complicações Hematológicas na Gravidez/economia , Avaliação de Programas e Projetos de Saúde , Isoimunização Rh/economia , Sistema do Grupo Sanguíneo Rh-Hr , Imunoglobulina rho(D)/economiaRESUMO
OBJECTIVE: This study aimed to evaluate serum-only four-marker first trimester (1T-Quad) Down syndrome screening, alone or contingently to select 10-20% with highest risk for nuchal translucency (NT) or cell-free (cf)DNA. METHODS: Stored maternal serum samples (-80 °C) from 90 pregnancies with fetal Down syndrome and 1607 controls were retrieved and measured for placental growth factor, α-fetoprotein, pregnancy-associated plasma protein and free ß-human chorionic gonadotropin. Samples were from singleton pregnancies (9-13 + 6 weeks), and NT was measured between 11 and 13 + 6 weeks. Markers were expressed in multiples of the normal median (MoM) for gestation. Gaussian models were fitted to the distribution of log MoMs by using observed parameters, standardized maternal age distribution (mean 27, SD 5.5) and published cfDNA results. RESULTS: The model-predicted detection rate (DR) for 1T-Quad was 74% [5% false-positive rate (FPR)]. When used contingently to select for NT, the DR was 89% at 5%. When used to select for cfDNA, the DR was 91% (FPR < 0.05%). CONCLUSION: The 1T-Quad test can achieve a similar DR to a second-trimester Quad test. When used contingently to select for NT, the DR is similar to the Combined test. Used contingently to select for cfDNA would achieve even higher detection.
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Biomarcadores/sangue , Análise Mutacional de DNA , Síndrome de Down/diagnóstico , Testes para Triagem do Soro Materno/métodos , Primeiro Trimestre da Gravidez/sangue , Diagnóstico Pré-Natal/métodos , Adulto , Estudos de Casos e Controles , Sistema Livre de Células , Gonadotropina Coriônica Humana Subunidade beta/sangue , DNA/sangue , Feminino , Humanos , Medição da Translucência Nucal , Fator de Crescimento Placentário , Gravidez , Proteínas da Gravidez/sangue , Proteína Plasmática A Associada à Gravidez/análise , Adulto Jovem , alfa-Fetoproteínas/análiseRESUMO
BACKGROUND: The role of men in the childbearing decision process and the factors that influence men's childbearing intentions have been relatively unexplored in the literature. This study aimed to describe the factors that strongly influence the childbearing intentions of men and to describe differences in these factors according to men's age group. METHODS: A telephone survey (response rate 84%) was conducted with 495 men between the ages of 20 and 45 living in an urban setting who, at the time of contact, did not have biological children. Men were asked about what factors strongly influence their intention to have children. Univariable and multivariable logistic regressions were conducted to determine if these factors were significantly associated with age. RESULTS: Of those sampled, 86% of men reported that at some point in the future they planned to become a parent. The factors that men considered to be most influential in their childbearing intentions were: the need to be financially secure, their partner's interest/desire to have children, their partner's suitability to be a parent and their personal interest/desire to have children. Men who were 35-45 years old had lower odds of stating that financial security (crude OR: 0.32, 95% CI: 0.18-0.54) and partner's interest in having children (crude OR: 0.57, 95% CI: 0.33-0.99) were very influential, but had higher odds of stating that their biological clock (crude OR: 4.37, 95% CI: 1.78-10.76) was very influential in their childbearing intentions than men in the 20-24 year age group. CONCLUSIONS: The factors that influence men's intentions about when to become a parent may change with age. Understanding what influences men to have children, and what they understand about reproductive health is important for education, program and policy development.
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Intenção , Comportamento Reprodutivo/psicologia , Adulto , Fatores Etários , Relógios Biológicos , Canadá , Humanos , Masculino , Idade Paterna , Fatores SexuaisRESUMO
UNLABELLED: Detailed consideration of the suggested association between calcium supplementation and heart attacks has revealed weakness in the evidence which make the hypothesis highly implausible. INTRODUCTION: The aim of this study was to evaluate the strength of the evidence that calcium supplementation increases the risk of myocardial infarction. METHODS: This study used critical examination of a meta-analysis of the effects of calcium supplements on heart attacks in five prospective trials on 8,016 men and women, and consideration of related publications by the same author. RESULTS: The meta-analysis was found to be subject to several limitations including non-adherence to the clinical protocol, multiple endpoint testing and failure to correctly adjust for endpoint ascertainment. The main risk factors for myocardial infarction were not available for 65% of the participants, and none of the trials had cardiovascular disease as its primary endpoint. There were more overweight participants, more subjects on thyroxine and more men on calcium than on placebo. In particular, over 65% of all the heart attacks were self-reported. When the evidence was considered in the light of Austin Bradford Hill's six main criteria for disease causation, it was found not to be biologically plausible or strong or to reflect a dose-response relationship or to be consistent or to reflect the relationship between the trends in calcium supplementation and heart attacks in the community or to have been confirmed by experiment. The addition of a more recent trial on 1,460 women over 5 years reduced the relative risk to 1.23 (P = 0.0695). CONCLUSION: Present evidence that calcium supplementation increases heart attacks is too weak to justify a change in prescribing habits.
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Cálcio da Dieta/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Metanálise como Assunto , Infarto do Miocárdio/induzido quimicamente , Atitude do Pessoal de Saúde , Medicina Baseada em Evidências , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa/normas , Fatores de RiscoRESUMO
BACKGROUND: We sought to identify which specific set of codes are used by each acute NHS trust in England to document the diagnosis and management of patellofemoral instability (PFI). METHODS: All acute NHS Trusts in England were sent freedom of information (FOI) requests regarding their use of International Statistical Classification of Diseases and Related Health Problems version 10 (ICD-10) codes for the diagnoses related to PFI, and Office of Population Censuses and Surveys Classification of Surgical Operations and Procedures 4th revision (OPCS-4) codes for surgical management of PFI. RESULTS: 106 of 132 (80%) relevant trusts who manage patients with PFI responded with information. Coding for diagnosis of patellar dislocation and recurrent dislocation were largely consistent with 96% of the trusts using the same code. However, coding of patellar instability varied widely with 10 different codes being used, the most common of which was being used by only 34% of trusts. Coding for operative management exhibited greater variety with the number of different codes being used by trusts for each of the eight surgical treatments ranging from 11 to 19 and the range for the most common code being used by trusts from 34% to 64%. Furthermore, a large number of trusts used multiple different codes for the same diagnosis or treatment of PFI. CONCLUSION: There is a lack of uniformity in how trusts code PFI diagnosis and treatment. Standardisation will enable further research involving focused analysis of trust databases to facilitate a better understanding of the epidemiology of this condition.
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Instabilidade Articular , Luxação Patelar , Articulação Patelofemoral , Inglaterra , Humanos , Instabilidade Articular/diagnóstico , Instabilidade Articular/cirurgia , Luxação Patelar/diagnóstico , Luxação Patelar/cirurgia , Articulação Patelofemoral/cirurgia , Inquéritos e QuestionáriosRESUMO
Endometriosis is a common benign condition affecting women. The disease has a broad spectrum of presentations from incidental lesions in asymptomatic women to causing significant and debilitating morbidity in others. Ectopic endometrial glands are located in predictable locations throughout the pelvis, including implantation on the ovaries and in the rectouterine cul-de-sac. Less commonly, the urinary tract may be involved. As genitourinary manifestations may remain symptomatically occult or masquerade as other diagnoses, it is essential for the radiologist to be aware of the imaging features, consider this diagnosis, and potentially save the patient from delayed treatment.
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Endometriose , Sistema Urinário , Endometriose/complicações , Endometriose/diagnóstico por imagem , Feminino , Humanos , Ovário , PelveRESUMO
Background: Readily available population-based data about cancer recurrence would improve surveillance and research for women of reproductive age. Methods: We randomly selected 200 women from the Alberta Cancer Registry who had received a cancer diagnosis and who ever had a pregnancy between 2003 and 2012. Administrative data were obtained and linked. Several definitions of recurrence were assessed using various minimum lengths of time between the initial diagnosis date and subsequent diagnoses or treatments, or both. Chart review was used as a "gold standard" definition of recurrence. Results: Chart review identified recurrences in 26 women. The definition that best captured "recurrence" was 2 or more cancer diagnosis codes 10 or more months from the diagnosis date [sensitivity: 80.8%; 95% confidence interval (ci): 60.7% to 93.5%; specificity: 81.0%; 95% ci: 74.4% to 86.6%; positive predictive value: 38.9%; 95% ci: 25.9% to 53.1%; negative predictive value: 96.6%; 95% ci: 92.2% to 98.9%; kappa = 0.42; 95% ci: 0.28 to 0.57]. Conclusions: Recurrence in reproductive-aged women can be captured with moderate validity using administrative data, but should be interpreted with caution.
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Neoplasias/epidemiologia , Adulto , Alberta , Algoritmos , Bases de Dados Factuais , Feminino , Humanos , Recidiva , Estudos de Validação como AssuntoRESUMO
INTRODUCTION: The International Methodology Consortium for Coded Health Information (IMeCCHI) is a collaboration of health services researchers who promote methodological advances in coded health information. The IMeCCHI-DATANETWORK initiative focuses on developing a multi-purpose distributed data infrastructure and common data model (CDM) to enable cross-border data sharing and international comparisons. METHODS: IMeCCHI consortium partners from six different countries - Canada, Denmark, Italy, New Zealand, South Korea, and Switzerland - used a questionnaire to describe their original databases which differ in size, structure, content and coding systems. To standardize these data, they agreed on a CDM and mapped their population-based databases to meet the CDM specifications. At the end of this process, local data had a more homogenous content and structure, which made them syntactically and semantically interoperable. Data transformation was performed using a common data management software called TheMatrix. RESULTS: The CDM encompasses four tables of structured data (person characteristics, hospitalizations, outpatient prescription medication and death), linked at the individual level through a person identifier. It can be used to answer research questions across countries using locally converted databases, which facilitates study replication in a distributed fashion. As a proof-of-concept study, an initial research question was addressed using an agreed protocol. Local data were transformed in csv files in the CDM structure and TheMatrix was tested to transform the standardized data from each partner into local analytical datasets. This allowed results to be shared between countries, whilst maintaining local control over each region's data. CONCLUSION: The IMeCCHI-DATANETWORK, a model of a distributed data network, demonstrated that it is feasible to analyze international data using standardized analytical methods that enable independent analyses by regions, without relocating datasets thereby protecting local confidentiality obligations. The distributed data infrastructure can produce results that can be generalized to several countries, while facilitating cross-border data sharing and international comparisons. KEYWORDS: Common data model, international comparison, cross-border data sharing, interoperability, observational data.
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BACKGROUND: Patellar instability is a relatively common condition that leads to disability and restriction of activities. People with recurrent instability may be given the option of physiotherapy or surgery though this is largely driven by clinician preference rather than by a strong evidence base. We sought to determine the feasibility of conducting a definitive trial comparing physiotherapy with surgical treatment for people with recurrent patellar instability. METHODS: This was a pragmatic, open-label, two-arm feasibility randomised control trial (RCT) with an embedded interview component recruiting across three NHS sites comparing surgical treatment to a package of best conservative care; 'Personalised Knee Therapy' (PKT). The primary feasibility outcome was the recruitment rate per centre (expected rate 1 to 1.5 participants recruited each month). Secondary outcomes included the rate of follow-up (over 80% expected at 12 months) and a series of participant-reported outcomes taken at 3, 6 and 12 months following randomisation, including the Norwich Patellar Instability Score (NPIS), the Kujala Patellofemoral Disorder Score (KPDS), EuroQol-5D-5L, self-reported global assessment of change, satisfaction at each time point and resources use. RESULTS: We recruited 19 participants. Of these, 18 participants (95%) were followed-up at 12 months and 1 (5%) withdrew. One centre recruited at just over one case per month, one centre was unable to recruit, and one centre recruited at over one case per month after a change in participant screening approach. Ten participants were allocated into the PKT arm, with nine to the surgical arm. Mean Norwich Patellar Instability Score improved from 40.6 (standard deviation 22.1) to 28.2 (SD 25.4) from baseline to 12 months. CONCLUSION: This feasibility trial identified a number of challenges and required a series of changes to ensure adequate recruitment and follow-up. These changes helped achieve a sufficient recruitment and follow-up rate. The revised trial design is feasible to be conducted as a definitive trial to answer this important clinical question for people with chronic patellar instability. TRIAL REGISTRATION: The trial was prospectively registered on the International Standard Randomised Controlled Trial Number registry on the 22/12/2016 (reference number: ISRCTN14950321). http://www.isrctn.com/ISRCTN14950321.
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In 2003, the UK Department of Health set out the genetics white paper, a plan for action and investment with particular emphasis on integration of genetic health care into primary care. Since the delivery of the genetics white paper, there has been little exploration of UK primary care doctors' attitudes towards extending their role to include provision of routine genetics services. We explored explore general practitioners' (GPs) attitudes towards provision of genetic health care including routine family history screening and familial risk assessment for common disorders in primary care using a quantitative, evaluative postal survey. Only 25% (797 of 3160) of the GPs returned a completed questionnaire. Although 32% of GPs supported collection of family history information and 41.5% familial risk assessment, 18% were not willing to offer these services even if training is provided. Of the GPs, 50% stated they recognized when referral to genetics services is appropriate, although 43% felt unprepared to collect family history or assess familial risk. Lack of training within the last 3 years was a significant predictor of feeling unprepared to undertake these activities (OR = 2.53,p = 0.012). A substantial group of GPs remain unprepared or unwilling to provide genetic health care. GPs' attitudes to delivery of genetic health care are significantly influenced by factors such as a lack of evidence of the direct benefits to patients, local guidelines and specialist services. These factors need addressing if delivery of genetic health care is to be incorporated into routine primary care.
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Atitude do Pessoal de Saúde , Predisposição Genética para Doença , Pesquisas sobre Atenção à Saúde/estatística & dados numéricos , Médicos de Família/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Demografia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Most normal cells require adhesion to extracellular matrix for survival, but the molecular mechanisms that link cell surface adhesion events to the intracellular apoptotic machinery are not understood. Bcl-2 family proteins regulate apoptosis induced by a variety of cellular insults through acting on internal membranes. A pro-apoptotic Bcl-2 family protein, Bax, is largely present in the cytosol of many cells, but redistributes to mitochondria after treatment with apoptosis-inducing drugs. Using mammary epithelial cells as a model for adhesion-regulated survival, we show that detachment from extracellular matrix induced a rapid translocation of Bax to mitochondria concurrent with a conformational change resulting in the exposure of its BH3 domain. Bax translocation and BH3 epitope exposure were reversible and occurred before caspase activation and apoptosis. Pp125FAK regulated the conformation of the Bax BH3 epitope, and PI 3-kinase and pp60src prevented apoptosis induced by defective pp125FAK signaling. Our results provide a mechanistic connection between integrin-mediated adhesion and apoptosis, through the kinase-regulated subcellular distribution of Bax.
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Apoptose/fisiologia , Sobrevivência Celular/fisiologia , Integrinas/fisiologia , Glândulas Mamárias Animais/citologia , Proteínas Proto-Oncogênicas c-bcl-2 , Proteínas Proto-Oncogênicas/química , Proteínas Proto-Oncogênicas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Adesão Celular , Linhagem Celular , Núcleo Celular/metabolismo , Núcleo Celular/ultraestrutura , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citosol/metabolismo , Citosol/ultraestrutura , Inibidores Enzimáticos/farmacologia , Feminino , Quinase 1 de Adesão Focal , Proteína-Tirosina Quinases de Adesão Focal , Camundongos , Camundongos Endogâmicos ICR , Fosfatidilinositol 3-Quinases/metabolismo , Poli-Hidroxietil Metacrilato/farmacologia , Gravidez , Conformação Proteica , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo , Proteínas Recombinantes/metabolismo , Transdução de Sinais/fisiologia , Frações Subcelulares/metabolismo , Frações Subcelulares/ultraestrutura , Transfecção , Proteína X Associada a bcl-2RESUMO
Little is understood about the regulation of gene expression in human preimplantation embryos. We set out to examine the expression in human preimplantation embryos of a number of genes known to be critical for early development of the murine embryo. The expression profile of these genes was analysed throughout preimplantation development and in response to growth factor (GF) stimulation. Developmental expression of a number of genes was similar to that seen in murine embryos (OCT3B/4, CDX2, NANOG). However, GATA6 is expressed throughout preimplantation development in the human. Embryos were cultured in IGF-I, leukaemia inhibitory factor (LIF) or heparin-binding EGF-like growth factor (HBEGF), all of which are known to stimulate the development of human embryos. Our data show that culture in HBEGF and LIF appears to facilitate human embryo expression of a number of genes: ERBB4 (LIF) and LIFR and DSC2 (HBEGF) while in the presence of HBEGF no blastocysts expressed EOMES and when cultured with LIF only two out of nine blastocysts expressed TBN. These data improve our knowledge of the similarities between human and murine embryos and the influence of GFs on human embryo gene expression. Results from this study will improve the understanding of cell fate decisions in early human embryos, which has important implications for both IVF treatment and the derivation of human embryonic stem cells.
Assuntos
Blastocisto/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Diferenciação Celular/genética , Células Cultivadas , Fase de Clivagem do Zigoto/metabolismo , Desenvolvimento Embrionário/efeitos dos fármacos , Desenvolvimento Embrionário/fisiologia , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Fator de Crescimento Semelhante a EGF de Ligação à Heparina , Humanos , Imuno-Histoquímica , Fator de Crescimento Insulin-Like I/farmacologia , Fator Inibidor de Leucemia/farmacologia , Mórula/metabolismo , Reação em Cadeia da Polimerase/métodos , Gravidez , Zigoto/metabolismoRESUMO
AIMS: Meniscal allograft transplantation is undertaken to improve pain and function in patients with a symptomatic meniscal deficient knee compartment. While case series have shown improvements in patient reported outcome measures (PROMs), its efficacy has not been rigorously evaluated. This study aimed to compare PROMs in patients having meniscal transplantation with those having personalized physiotherapy at 12 months. PATIENTS AND METHODS: A single-centre assessor-blinded, comprehensive cohort study, incorporating a pilot randomized controlled trial (RCT) was performed on patients with a symptomatic compartment of the knee in which a (sub)total meniscectomy had previously been performed. They were randomized to be treated either with a meniscal allograft transplantation or personalized physiotherapy, and stratified for malalignment of the limb. They entered the preference groups if they were not willing to be randomized. The Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) score and Lysholm score and complications were collected at baseline and at four, eight and 12 months following the interventions. RESULTS: A total of 36 patients entered the study; 21 were randomized and 15 chose their treatments. Their mean age was 28 years (range 17 to 46). The outcomes were similar in the randomized and preference groups, allowing pooling of data. At 12 months, the KOOS4 composite score (mean difference 12, p = 0.03) and KOOS subscales of pain (mean difference 15, p = 0.02) and activities of daily living (mean difference 18, p = 0.005) were significantly superior in the meniscal transplantation group. Other PROMs also favoured this group without reaching statistical significance. There were five complications in the meniscal transplantation and one in the physiotherapy groups. CONCLUSION: This is the first study to compare meniscal allograft transplantation to non-operative treatment. The results provide the best quality evidence to date of the symptomatic benefits of meniscal allograft transplantation in the short term, but a multicentre RCT is required to investigate this question further. Cite this article: Bone Joint J 2018;100-B:56-63.
Assuntos
Terapia por Exercício/métodos , Meniscos Tibiais/transplante , Lesões do Menisco Tibial/cirurgia , Atividades Cotidianas , Adolescente , Adulto , Terapia por Exercício/efeitos adversos , Feminino , Humanos , Traumatismos do Joelho/cirurgia , Masculino , Meniscectomia , Meniscos Tibiais/cirurgia , Medidas de Resultados Relatados pelo Paciente , Projetos Piloto , Complicações Pós-Operatórias , Medicina de Precisão/métodos , Índice de Gravidade de Doença , Método Simples-Cego , Lesões do Menisco Tibial/etiologia , Adulto JovemRESUMO
Aims: This study reports on the medium- to long-term implant survivorship and patient-reported outcomes for the Avon patellofemoral joint (PFJ) arthroplasty. Patients and Methods: A total of 558 Avon PFJ arthroplasties in 431 patients, with minimum two-year follow-up, were identified from a prospective database. Patient-reported outcomes and implant survivorship were analyzed, with follow-up of up to 18 years. Results: Outcomes were recorded for 483 implants (368 patients), representing an 86% follow-up rate. The median postoperative Oxford Knee Score (0 to 48 scale) was 35 (interquartile range (IQR) 25.5 to 43) and the median Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC, 0 to 100 scale) was 35 (IQR 25 to 53) at two years. There were 105 revisions, 61 (58%) for progression of osteoarthritis. All documented revisions were to primary knee systems without augmentation. The implant survival rate was 77.3% (95% confidence interval (CI) 72.4 to 81.7, number at risk 204) at ten years and 67.4% (95% CI 72.4 to 81.7 number at risk 45) at 15 years. Regression analysis of explanatory data variable showed that cases performed in the last nine years had improved survival compared with the first nine years of the cohort, but the individual operating surgeon had the strongest effect on survivorship. Conclusion: Satisfactory long-term results can be obtained with the Avon PFJ arthroplasty, with maintenance of patient-reported outcome measures (PROMs), satisfactory survival, and low rates of loosening and wear. Cite this article: Bone Joint J 2018;100-B:1162-7.
Assuntos
Artroplastia do Joelho/métodos , Osteoartrite do Joelho/cirurgia , Articulação Patelofemoral/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Joelho/efeitos adversos , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Prótese do Joelho/efeitos adversos , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Falha de Prótese , Reoperação/estatística & dados numéricos , Análise de Sobrevida , Resultado do TratamentoRESUMO
This paper investigates a Spatial Neyman-Scott Rectangular Pulse (SNSRP) model, which is one of only a few models capable of continuous simulation of rainfall in both space and time. The SNSRP is a spatial extension of the Neyman-Scott Rectangular Pulse model at a single point. The model is highly idealized having six parameters: storm arrival, cell arrival, cell radius, cell lifetime and two cell intensity parameters. A spatial interpolation of the scale parameter is used so that the model can be simulated continuously in space, rather than as a multi-site model. The parameters are calibrated using least-squares fits to statistical moments based on data aggregated to hourly and daily totals. The SNSRP model is calibrated to a very large network of 85 gauges over metropolitan Sydney and shows a good agreement to calibrated statistics. A simulation of 50 replicates over the region compares favourably to several observed temporal statistics, with an example given for one site. A qualitative discussion of the simulated spatial images demonstrates the underlying structure of non-advecting cylindrical cells.
Assuntos
Modelos Teóricos , Chuva , Austrália , Simulação por Computador , Geografia , Movimentos da ÁguaRESUMO
AIMS: The Bereiter trochleoplasty has been used in our unit for 12 years to manage recurrent patellar instability in patients with severe trochlea dysplasia. The aim of this study was to document the outcome of a large consecutive cohort of patients who have undergone this operation. PATIENTS AND METHODS: Between June 2002 and August 2013, 214 consecutive trochleoplasties were carried out in 185 patients. There were 133 women and 52 men with a mean age of 21.3 years (14 to 38). All patients were offered yearly clinical and radiological follow-up. They completed the following patient reported outcome scores (PROMs): International Knee Documentation Committee subjective scale, the Kujala score, the Western Ontario and McMaster Universities Arthritis Index score and the short-form (SF)-12. RESULTS: Outcomes were available for 199 trochleoplasties in 173 patients giving a 93% follow-up rate at a mean of 4.43 years (1 to 12). There were no infections or deep vein thromboses. In total, 16 patients reported further patella dislocation, giving an 8.3% rate of recurrence. There were 27 re-operations, giving a rate of re-operation of 14%. Overall, 88% were satisfied with the operation and 90% felt that their symptoms had been improved. CONCLUSION: All PROMs improved significantly post-operatively except for the mental component score of the SF-12. Trochleoplasty performed using a flexible osteochondral flap is an effective treatment for recurrent patellar instability in patients with severe trochlea dysplasia and gives good results in the medium term. Cite this article: Bone Joint J 2017;99-B:344-50.