Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 33
Filtrar
Filtros adicionais











País/Região como assunto
Intervalo de ano
2.
Pharmacoecon Open ; 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31054048

RESUMO

INTRODUCTION: Cystic fibrosis (CF) is a life-limiting, hereditable condition, with the highest prevalence in Europe. CF treatments have led to improvements in clinical symptoms, disease management and decelerated disease progression. However, little is known about the health state utility (HSU) associated with CF disease states, adverse events, and changes in disease severity. Although HSU data have contributed to existing health economic modelling studies, a lack of such data have been highlighted. This systematic review aims to provide a summary of HSU-related research in CF and highlight related research gaps. METHODS: Online searches were performed in six databases and studies in any of the following categories were included: (1) estimation of HSUs in CF; (2) mapping studies between patient-reported outcome measures (PROMs) and HSUs; (3) economic evaluations on the management of CF that report primary HSU data; and (4) any CF clinical trial that reported HSU as an outcome. RESULTS: A total of 17 studies were reviewed, of which 12 provided HSU values for specific CF populations. The remaining five articles provided HSU data that were broken down by CF relevant health states, including lung transplantations, pulmonary exacerbation (PEx) events and forced expiratory volume in 1 s (FEV1). CONCLUSION: Current HSU data in CF are limited and there is considerable scope for further research, both in providing HSU values for CF and in investigating methods for HSU elicitation/evaluation in CF populations.

3.
J Cyst Fibros ; 18(4): 452-460, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30738801

RESUMO

INTRODUCTION: Cystic Fibrosis (CF) is a heritable chronic condition. Due to the genetic and progressive nature of CF, a number of interventions are available for the condition. In the United Kingdom (U.K.) average annual cost of CF treatment is between €49,000 to €76,000 (2012) per patient [1]. A review of health economic modelling studies is warranted to provide decision makers and researchers with an in depth understanding of modelling practices in CF and guidance for future research. METHODS: Online searches were performed in the 5 databases, studies were included if they were: a) Model based economic evaluation for management of Cystic Fibrosis. Articles were restricted to English language only, but no restriction was applied on publication year. RESULTS: Nine studies were reviewed, most were Markov cohort models. Models evaluated pharmaceutical interventions and drug adherence. Modelling structure was consistent across most articles and a range of sources were used to populate the models. Cost and utility data were based on different sources and elicitation methods respectively. The majority of models failed to incorporate significant health events which impact both cost and disease progression. CONCLUSION: In our review we observed a lack of, application of European Medicines Agency (EMA) guidelines for clinical trial endpoints, model structure justifications and lastly, health-related quality of life derived utility information around important clinical events. Future work around conceptual modelling of CF progression, utility valuation of significant health events and meeting EMA guidelines for trial reporting is encouraged.

4.
J Cyst Fibros ; 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30503032

RESUMO

BACKGROUND: Non-invasive ventilation (NIV) for respiratory failure and airway clearance is an established intervention in cystic fibrosis (CF), but its therapeutic benefit on lung function and survival remains under-investigated. METHODS: Using data from the UK CF Registry between 2007 and 2015, we explored the patterns of NIV use, and assessed changes in mean percent predicted FEV1 (ppFEV1) prior to and after NIV use, and the survival of patients on NIV. RESULTS: Among 11,079 patients, 1107 had at least one record of NIV treatment. Incidence and prevalence of NIV was lower in children and followed non-linear temporal patterns. Adjusting for other risk factors, ppFEV1 rose by 0.70 (95%CI: -0.83, 2.24) after first NIV use in children. In adults with a low ppFEV1 (<40%) at initiation of treatment, NIV increased mean ppFEV1 by 2.60 (95% CI: 0.93, 4.27). Our analysis showed that NIV initiation is associated with an increased risk of death/transplant in both children (HR = 2.47; 95%CI: 1.20-5.08) and adults (HR = 1.96; 95% CI: 1.63-2.36) but effect was attenuated in children with low ppFEV1 (<40%). CONCLUSIONS: NIV usage in CF improves spirometric values but does not benefit survival. Further studies are required to better understand survival outcomes and ultimately improve NIV outcomes in CF.

5.
Am J Hum Genet ; 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30471717

RESUMO

Motile cilia move body fluids and gametes and the beating of cilia lining the airway epithelial surfaces ensures that they are kept clear and protected from inhaled pathogens and consequent respiratory infections. Dynein motor proteins provide mechanical force for cilia beating. Dynein mutations are a common cause of primary ciliary dyskinesia (PCD), an inherited condition characterized by deficient mucociliary clearance and chronic respiratory disease coupled with laterality disturbances and subfertility. Using next-generation sequencing, we detected mutations in the ciliary outer dynein arm (ODA) heavy chain gene DNAH9 in individuals from PCD clinics with situs inversus and in one case male infertility. DNAH9 and its partner heavy chain DNAH5 localize to type 2 ODAs of the distal cilium and in DNAH9-mutated nasal respiratory epithelial cilia we found a loss of DNAH9/DNAH5-containing type 2 ODAs that was restricted to the distal cilia region. This confers a reduced beating frequency with a subtle beating pattern defect affecting the motility of the distal cilia portion. 3D electron tomography ultrastructural studies confirmed regional loss of ODAs from the distal cilium, manifesting as either loss of whole ODA or partial loss of ODA volume. Paramecium DNAH9 knockdown confirms an evolutionarily conserved function for DNAH9 in cilia motility and ODA stability. We find that DNAH9 is widely expressed in the airways, despite DNAH9 mutations appearing to confer symptoms restricted to the upper respiratory tract. In summary, DNAH9 mutations reduce cilia function but some respiratory mucociliary clearance potential may be retained, widening the PCD disease spectrum.

6.
J Cyst Fibros ; 2018 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-30343891

RESUMO

BACKGROUND: Many risk factors for lung disease in cystic fibrosis (CF) display a seasonal pattern yet it is unclear whether this is reflected in seasonal fluctuations in lung function. METHODS: We conducted a longitudinal study using CF registries in Denmark and the UK. 471 individuals with a median of 104 FEV1 measurements per person and 7586 individuals with a median of nine FEV1 measures per person were included from Denmark and the UK respectively. We estimated the effect of seasonality on percent predicted FEV1 trajectories using mixed effects models whilst adjusting for clinically important covariates. RESULTS: We found no significant cyclical seasonal variation in lung function in either country. The maximum variation in percent predicted FEV1 around the yearly average was estimated to be 0.1 percentage points (95%CI 0 to 0.21) and 0.14 percentage points (95%CI 0 to 0.29) in Denmark and the UK, respectively. When considering possible step-like changes between the four seasons, we found that lung function was higher in spring compared to winter in the UK (0.34 percentage points, 95%CI 0.1 to 0.59) though the difference was not of clinical significance. CONCLUSION: In both the UK and Denmark there may be small seasonal changes in lung function but this effect is not of clinical importance.

7.
J Cyst Fibros ; 2018 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-30366848

RESUMO

BACKGROUND: We aimed to establish a national cystic fibrosis (CF) registry for Cuba, a developing country. METHODS: Regional centres that deliver care for all CF patients provided information for a national database. FINDINGS: The prevalence of CF in Cuba is 26.3 cases per 1,000,000 population. The median age at diagnosis is 2 years, and the median age of the total population was 15 years. Of those aged 16 years or older, the prevalence of Pseudomonas aeruginosa infection was 46%, the prevalence of Staphylococcus aureus infection was 36%, and 80% of individuals were receiving oral azithromycin. The commonest gene mutation was F508del which was observed in 50% of patients. INTERPRETATION: These data demonstrate that it is possible to establish a national CF registry in a developing country such as Cuba. This provides baseline data to permit evaluation of health care delivery enable the spread of good clinical practice nationally.

8.
Thorax ; 2018 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-30026297

RESUMO

BACKGROUND: Poor growth during infancy and childhood is a characteristic feature of cystic fibrosis (CF). However, the impact of CF on intrauterine growth is unclear. We studied the effect of CF on birth weight in Denmark and Wales, and assessed whether any associations are due to differences in gestational age at birth. METHODS: We conducted national registry linkage studies in two countries, using data for 2.2 million singletons born in Denmark (between 1980 and 2010) and Wales (between 1998 and 2015). We used hospital inpatient and outpatient data to identify 852 children with CF. Using causal mediation methods, we estimated the direct and indirect (via gestational age) effect of CF on birth weight after adjustment for sex, parity and socioeconomic background. We tested the robustness of our results by adjusting for additional factors such as maternal smoking during pregnancy in subpopulations where these data were available. RESULTS: Babies with CF were more likely to be born preterm and with low birth weight than babies with no CF (12.7% vs 5% and 9.4% vs 5.8% preterm; 11.9% vs 4.2% and 11% vs 5.4% low birth weight in Denmark and Wales, respectively). Using causal mediation methods, the total effect of CF on birth weight was estimated to be -178.8 g (95% CI -225.43 to -134.47 g) in the Danish population and -210.08 g (95% CI -281.97 to -141.5 g) in the Welsh population. About 40% of this effect of CF on birth weight was mediated through gestational age. CONCLUSIONS: CF significantly impacts on intrauterine growth and leads to lower birth weight in babies with CF, which is only partially explained by shorter gestation.

10.
Paediatr Respir Rev ; 27: 9-12, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29703693

RESUMO

Hypersensitivity reactions to intravenous antibiotics are common in cystic fibrosis (CF). As well as causing immediate morbidity, the need for future avoidance of the causative antibiotic can have a long-term negative impact on CF management. This paper reviews the epidemiology and clinical presentation of hypersensitivity reactions in CF patients, and using an illustrative case describes a rare but severe form of delayed drug reaction for which a high index of suspicion is required.

12.
J Cyst Fibros ; 17(6): 791-797, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29329721

RESUMO

BACKGROUND: Cystic fibrosis related diabetes (CFRD) is associated with increased morbidity in CF. Variability in physiological systems is associated with dysfunctional homeostasis. We examined whether fluctuation in glucose is a marker of CFRD or "pre-diabetes". METHODS: Using a machine learning approach, we compared glucose IQR to current diagnostic criteria in a review of continuous glucose monitoring data. RESULTS: Analysis was performed on 248 studies from 142 children. Calculated IQR (cIQR) was increased between children with CFRD, normal glucose homeostasis and indeterminate status (p<0.0001) and impaired glucose tolerance (p<0.05, Kruskal-Wallis test). In subjects who developed CFRD (n=20), cIQR increased between baseline and diagnosis (1.4mmol/L versus 2.4mmol/L, p<0.0001, Wilcoxon test). Area under the curve for CFRD on the basis of cIQR was 0.865 (p<0.0001). Neither episodes of hypoglycaemia nor cIQR at baseline predicted CFRD. CONCLUSIONS: Glucose fluctuation on CGMS can be quantified by calculating the IQR. This information may improve early recognition of abnormal glucose homeostasis.

13.
Thorax ; 73(2): 157-166, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28790179

RESUMO

RATIONALE: Primary ciliary dyskinesia is a genetically heterogeneous inherited condition characterised by progressive lung disease arising from abnormal cilia function. Approximately half of patients have situs inversus. The estimated prevalence of primary ciliary dyskinesia in the UK South Asian population is 1:2265. Early, accurate diagnosis is key to implementing appropriate management but clinical diagnostic tests can be equivocal. OBJECTIVES: To determine the importance of genetic screening for primary ciliary dyskinesia in a UK South Asian population with a typical clinical phenotype, where standard testing is inconclusive. METHODS: Next-generation sequencing was used to screen 86 South Asian patients who had a clinical history consistent with primary ciliary dyskinesia. The effect of a CCDC103 p.His154Pro missense variant compared with other dynein arm-associated gene mutations on diagnostic/phenotypic variability was tested. CCDC103 p.His154Pro variant pathogenicity was assessed by oligomerisation assay. RESULTS: Sixteen of 86 (19%) patients carried a homozygous CCDC103 p.His154Pro mutation which was found to disrupt protein oligomerisation. Variable diagnostic test results were obtained including normal nasal nitric oxide levels, normal ciliary beat pattern and frequency and a spectrum of partial and normal dynein arm retention. Fifteen (94%) patients or their sibling(s) had situs inversus suggesting CCDC103 p.His154Pro patients without situs inversus are missed. CONCLUSIONS: The CCDC103 p.His154Pro mutation is more prevalent than previously thought in the South Asian community and causes primary ciliary dyskinesia that can be difficult to diagnose using pathology-based clinical tests. Genetic testing is critical when there is a strong clinical phenotype with inconclusive standard diagnostic tests.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Síndrome de Kartagener/etnologia , Síndrome de Kartagener/genética , Proteínas Associadas aos Microtúbulos/genética , Mutação/genética , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Paquistão/etnologia , Reino Unido , Adulto Jovem
15.
Eur Respir J ; 50(6)2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29269581

RESUMO

Chronic respiratory disease can affect growth and nutrition, which can influence lung function. We investigated height, body mass index (BMI), and lung function in patients with primary ciliary dyskinesia (PCD).In this study, based on the international PCD (iPCD) Cohort, we calculated z-scores for height and BMI using World Health Organization (WHO) and national growth references, and assessed associations with age, sex, country, diagnostic certainty, age at diagnosis, organ laterality and lung function in multilevel regression models that accounted for repeated measurements.We analysed 6402 measurements from 1609 iPCD Cohort patients. Height was reduced compared to WHO (z-score -0.12, 95% CI -0.17 to -0.06) and national references (z-score -0.27, 95% CI -0.33 to -0.21) in male and female patients in all age groups, with variation between countries. Height and BMI were higher in patients diagnosed earlier in life (p=0.026 and p<0.001, respectively) and closely associated with forced expiratory volume in 1 s and forced vital capacity z-scores (p<0.001).Our study indicates that both growth and nutrition are affected adversely in PCD patients from early life and are both strongly associated with lung function. If supported by longitudinal studies, these findings suggest that early diagnosis with multidisciplinary management and nutritional advice could improve growth and delay disease progression and lung function impairment in PCD.

16.
Eur Respir J ; 50(5)2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29122914

RESUMO

With the advent of novel designer molecules for cystic fibrosis (CF) treatment, there is huge need for early-life clinical trial outcomes, such as infant lung function (ILF). We investigated the degree and tracking of ILF abnormality during the first 2 years of life in CF newborn screened infants.Forced expiratory volume in 0.5 s (FEV0.5), lung clearance index (LCI) and plethysmographic functional residual capacity were measured at ∼3 months, 1 year and 2 years in 62 infants with CF and 34 controls.By 2 years there was no significant difference in FEV0.5 z-score between CF and controls, whereas mean LCI z-score was 0.81 (95% CI 0.45-1.17) higher in CF. However, there was no significant association between LCI z-score at 2 years with either 3-month or 1-year results. Despite minimal average group changes in any ILF outcome during the second year of life, marked within-subject changes occurred. No child had abnormal LCI or FEV0.5 on all test occasions, precluding the ability to identify "high-risk" infants in early life.In conclusion, changes in lung function are mild and transient during the first 2 years of life in newborn screened infants with CF when managed according to a standardised UK treatment protocol. Their potential role in tracking disease to later childhood will be ascertained by ongoing follow-up.


Assuntos
Fibrose Cística/diagnóstico , Fibrose Cística/fisiopatologia , Pulmão/fisiopatologia , Triagem Neonatal , Estudos de Casos e Controles , Feminino , Volume Expiratório Forçado , Capacidade Residual Funcional , Humanos , Lactente , Recém-Nascido , Masculino , Análise de Regressão , Reino Unido
17.
Pediatr Pulmonol ; 52(3): 279-280, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28221735
18.
Eur Spine J ; 26(6): 1595-1599, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28180983

RESUMO

PURPOSE: Primary ciliary dyskinesia (PCD) is a respiratory syndrome in which 'random' organ orientation can occur; with approximately 46% of patients developing situs inversus totalis at organogenesis. The aim of this study was to explore the relationship between organ anatomy and curve convexity by studying the prevalence and convexity of idiopathic scoliosis in PCD patients with and without situs inversus. METHODS: Chest radiographs of PCD patients were systematically screened for existence of significant lateral spinal deviation using the Cobb angle. Positive values represented right-sided convexity. Curve convexity and Cobb angles were compared between PCD patients with situs inversus and normal anatomy. RESULTS: A total of 198 PCD patients were screened. The prevalence of scoliosis (Cobb >10°) and significant spinal asymmetry (Cobb 5-10°) was 8 and 23%, respectively. Curve convexity and Cobb angle were significantly different within both groups between situs inversus patients and patients with normal anatomy (P ≤ 0.009). Moreover, curve convexity correlated significantly with organ orientation (P < 0.001; ϕ = 0.882): In 16 PCD patients with scoliosis (8 situs inversus and 8 normal anatomy), except for one case, matching of curve convexity and orientation of organ anatomy was observed: convexity of the curve was opposite to organ orientation. CONCLUSIONS: This study supports our hypothesis on the correlation between organ anatomy and curve convexity in scoliosis: the convexity of the thoracic curve is predominantly to the right in PCD patients that were 'randomized' to normal organ anatomy and to the left in patients with situs inversus totalis.


Assuntos
Síndrome de Kartagener/patologia , Escoliose/patologia , Situs Inversus/patologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Síndrome de Kartagener/complicações , Síndrome de Kartagener/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Prevalência , Radiografia , Escoliose/diagnóstico por imagem , Escoliose/epidemiologia , Escoliose/etiologia , Situs Inversus/complicações , Situs Inversus/diagnóstico por imagem , Adulto Jovem
19.
Expert Rev Respir Med ; : 1-13, 2016 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-27680603

RESUMO

INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare, mostly autosomal-recessive disorder of motile cilia, characterized by chronic lung disease, rhinosinusitis, hearing impairment, and subfertility. PCD is still often missed or diagnosed late since symptoms overlap with common respiratory complaints, but should be considered if one or more of the cardinal clues are present. Areas covered: We provide an overview on clinical presentations of PCD and clues for when to consider PCD, these include unexplained neonatal respiratory distress, persistent rhinitis from the first days of life, situs anomalies, or otorrhoea following tympanostomy tube insertion. Diagnosis is on the basis of clinical suspicion, and an algorithm of nasal nitric oxide, ciliary beat pattern and frequency, transmission electron microscopy, immunofluorescence of ciliary proteins and genetic studies. However, there is no one gold-standard test as yet. We reviewed the current literature based on PubMed and Ovid databases literature search. Expert commentary: There is a need for increased awareness about PCD beyond specialist respiratory clinicians and a need for standardization of PCD diagnostics internationally. Early diagnosis means that inappropriate treatment based on misdiagnosed conditions can be avoided, and the onset of bronchiectasis may be delayed.

20.
Pediatr Pulmonol ; 51(12): 1362-1366, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27273679

RESUMO

RATIONALE: Spirometry in children with cystic fibrosis (CF) frequently fails to return to baseline after treatment for a pulmonary exacerbation. It is unclear whether the same is true for children with primary ciliary dyskinesia (PCD). OBJECTIVES: To determine in children with PCD treated with intravenous antibiotics for a pulmonary exacerbation: (1) the proportion who recover to baseline forced expiratory volume at 1 sec (FEV1 ) within 3 months after treatment and (2) to try to identify factors which are associated with failure to regain pre-exacerbation FEV1 . METHODS: Cohort study using the PCD database for children at the Royal Brompton Hospital, 2003-2013. We selected the first pulmonary exacerbation treated with intravenous antibiotics. The best FEV1 within 3 months after treatment was compared to the best FEV1 in the 12 months before treatment (baseline). Recovery to baseline was defined as any FEV1 after treatment that was greater than or equal to 90% of the baseline FEV1 . RESULTS: 32/150 children (21%) had at least one pulmonary exacerbation. 23/30 (77%) regained baseline spirometry within 3 months of treatment. There was no difference between responders and non-responders in any baseline characteristics. CONCLUSIONS: Around 25% of children with PCD fail to recover to baseline lung function within 3 months following treatment for a pulmonary exacerbation, similar to CF. Better treatment strategies are needed, and the results also suggest that prevention of exacerbations would be a useful end-point in clinical trials. Pediatr Pulmonol. 2016;51:1362-1366. © 2016 Wiley Periodicals, Inc.


Assuntos
Antibacterianos/uso terapêutico , Síndrome de Kartagener/fisiopatologia , Pulmão/fisiopatologia , Recuperação de Função Fisiológica , Infecções Respiratórias/tratamento farmacológico , Adolescente , Criança , Estudos de Coortes , Bases de Dados Factuais , Progressão da Doença , Feminino , Volume Expiratório Forçado , Humanos , Síndrome de Kartagener/complicações , Síndrome de Kartagener/tratamento farmacológico , Masculino , Infecções Respiratórias/complicações , Infecções Respiratórias/fisiopatologia , Estudos Retrospectivos , Espirometria
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA