The Effect of Health Literacy on Medication Knowledge and Medication Discrepancy in Chinese Americans.

Background. Functional health literacy (FHL) is increasingly recognized as a useful predictor of health outcomes in different populations. However, the effect of FHL on medication knowledge and medication discrepancy in Chinese Americans is not well defined. Objectives. To examine the effects of FHL on medication knowledge and medication discrepancy in Chinese American patients. Methods. This was a cross-sectional study conducted at an academic internal medicine clinic. The Short Test of Functional Health Literacy in Adults was used to assess participants' FHL. Data for patients' demographic information, medication knowledge, and medication discrepancy (direction discrepancy and name discrepancy) were collected through patient interviews and chart reviews. The primary outcome was medication knowledge of purpose and the secondary outcomes included medication direction discrepancy and medication name discrepancy. Results. Of the 158 Chinese American patients who participated in the study, 54% had adequate FHL. More participants with adequate FHL had correct medication knowledge compared to participants with inadequate FHL (87% vs 56%, respectively, odds ratio = 3.4, 95% confidence interval = 1.2-9.7). Fewer participants with adequate FHL had medication direction discrepancy compared to those with inadequate FHL (42% vs 62%, odds ratio = 0.18, 95% confidence interval = 0.06-0.55). Both adequate and inadequate FHL groups had high prevalence of medication name discrepancy (77% vs 89%) even though the between-group difference was insignificant. Conclusions. Adequate FHL among Chinese American patients is significantly associated with increased medication knowledge of purpose and decreased medication direction discrepancy. Both adequate and inadequate FHL groups had high prevalence of medication name discrepancy.

A methodology to establish a database to study gene environment interactions for childhood asthma.

BACKGROUND: Gene-environment interactions are likely to explain some of the heterogeneity in childhood asthma. Here, we describe the methodology and experiences in establishing a database for childhood asthma designed to study gene-environment interactions (PAGES--Paediatric Asthma Gene Environment Study). METHODS: Children with asthma and under the care of a respiratory paediatrician are being recruited from 15 hospitals between 2008 and 2011. An asthma questionnaire is completed and returned by post. At a routine clinic visit saliva is collected for DNA extraction. Detailed phenotyping in a proportion of children includes spirometry, bronchodilator response (BDR), skin prick reactivity, exhaled nitric oxide and salivary cotinine. Dietary and quality of life questionnaires are completed. Data are entered onto a purpose-built database. RESULTS: To date 1045 children have been invited to participate and data collected in 501 (48%). The mean age (SD) of participants is 8.6 (3.9) years, 57% male. DNA has been collected in 436 children. Spirometry has been obtained in 172 children, mean % predicted (SD) FEV1 97% (15) and median (IQR) BDR is 5% (2, 9). There were differences in age, socioeconomic status, severity and %FEV1 between the different centres (p≤0.024). Reasons for non-participation included parents not having time to take part, children not attending clinics and, in a small proportion, refusal to take part. CONCLUSIONS: It is feasible to establish a national database to study gene-environment interactions within an asthmatic paediatric population; there are barriers to participation and some different characteristics in individuals recruited from different centres. Recruitment to our study continues and is anticipated to extend current understanding of asthma heterogeneity.

Cystic fibrosis across Europe: EuroCareCF analysis of demographic data from 35 countries.

BACKGROUND: A 35-country European cystic fibrosis (CF) demographic registry was developed to compare outcomes (EuroCareCF EC-FP6). METHODS: We applied methods that had successfully created country-specific registries inviting wide participation to obtain consent and collate demographic and CFTR genotype data. RESULTS: Among 29,095 patients, a widely different country-specific prevalence of childhood CF exists that cannot be explained by differential population frequency of mutant-CFTR or case under-ascertainment with a significant paucity of the homozygous p.Phe508del genotype that presents in childhood in >90% of cases. CONCLUSIONS: Excess premature childhood CF mortality may still occur. The better resourced Western Europe now has a ~5% mortality for childhood CF, which is not apparent in many of the European countries reported here. In addition, a female survival disadvantage exists. The reasons require further investigation. We showcase the value of simple data collection in one rare disease, which might interest those managing rare diseases across the globe.

Comparative demographics of the European cystic fibrosis population: a cross-sectional database analysis.

BACKGROUND: Country-specific patients' registries are rarely used to make international comparisons because of protocol discrepancies in data collation. We present data from a European cystic fibrosis registry that is dedicated to collection of demographic data, and assess whether the resources available in countries with and without European Union (EU) membership affects care and survival of patients. METHODS: Data for demographic indicators-age, age at diagnosis, sex, and genotype-for patients with cystic fibrosis from 35 European countries were combined, and used to establish the differences in demographic indicators between EU and non-EU countries. EU membership status in 2003 was used to divide countries. We modelled demographic indicators of EU countries on non-EU countries to estimate the size of the cystic fibrosis population if non-EU countries had had the same resources available for patients as did EU countries. FINDINGS: Data were gathered for 29 025 patients, who had a median age of 16.3 years (IQR 8.9-24.8), with a difference of 4.9 years (95% CI 4.4-5.1; p<0.0001) between EU (median 17.0 years, IQR 9.5-25.6) and non-EU countries (12.1 years, 6.0-19.2). The proportion of patients older than 40 years was higher in EU countries (1205 [5%]) than in non-EU countries (76 [2%]), with an odds ratio of 2.4 (95% CI 1.9-3.0, p<0.0001). We estimated that the cystic fibrosis population in non-EU countries would increase by 84% if patients had a demographic profile comparable to that of patients in EU countries. INTERPRETATION: Future studies need to establish the reasons for the lower proportion of patients with cystic fibrosis in non-EU countries than in EU countries, such as underdiagnosis and premature childhood mortality. FUNDING: European Community's Sixth Framework Programme for Research, and Czech Ministry of Health.

European best practice guidelines for cystic fibrosis neonatal screening.

There is wide agreement on the benefits of NBS for CF in terms of lowered disease severity, decreased burden of care, and reduced costs. Risks are mainly associated with disclosure of carrier status and diagnostic uncertainty. When starting a NBS programme for CF it is important to take precautions in order to minimise avoidable risks and maximise benefits. In Europe more than 25 screening programmes have been developed, with quite marked variation in protocol design. However, given the wide geographic, ethnic, and economic variations, complete harmonisation of protocols is not appropriate. There is little evidence to support the use of IRT alone as a second tier, without involving DNA mutation analysis. However, if IRT/DNA testing does not lead to the desired specificity/sensitivity ratio in a population, a screening programme based on IRT/IRT may be used. Sweat chloride concentration remains the gold standard for discriminating between NBS false and true positives, but age-related changes in sweat chloride should be taken into account. CF phenotypes associated with less severe disease often have intermediate or normal sweat chloride concentrations. Programmes should include arrangements for counselling and management of infants where the diagnosis is not clear-cut. All newborns identified by NBS should be managed according to internationally accepted guidelines. CF centre care and the availability of necessary medication are essential prerequisites before the introduction of NBS programmes. Clear explanation to families of the process of screening and of implications of normal and abnormal results is central to the success of CF NBS programmes. Effective communication is especially important when parents are told that their child is affected or is a carrier. When establishing a NBS programme for CF, attention should be given to ensuring timely and appropriate processing of results, to minimise potential stress for families.

Economic implications of newborn screening for cystic fibrosis: a cost of illness retrospective cohort study.

BACKGROUND: Newborn screening for cystic fibrosis might not be introduced if implementation and running costs are perceived as prohibitive. Compared with clinical diagnosis, newborn screening is associated with clinical benefit and reduced treatment needs. We estimate the potential savings in treatment costs attributable to newborn screening. METHODS: Using the UK Cystic Fibrosis Database, we used a prevalence strategy to undertake a cost of illness retrospective snapshot cohort study. We estimated yearly costs of long-term therapies and intravenous antibiotics for 184 patients who were diagnosed as a result of screening as newborn babies, and 950 patients who were clinically diagnosed aged 1-9 years in 2002. Costs of adding cystic fibrosis screening to an established newborn screening service in Scotland were adjusted to 2002 prices and applied to the UK as a whole. Costs were recalculated in US$. FINDINGS: Cost of therapy for patients diagnosed by newborn screening was significantly lower than equivalent therapies for clinically diagnosed patients: mean ($7228 vs $12 008, 95% CI of difference -6736 to -2028, p<0.0001) and median ($352 vs $2442, -1916 to -180, p<0.0001). When we limited the clinically diagnosed group to only those diagnosable with a 31 cystic fibrosis transmembrane regulator mutation assay and assumed similar disease progression in the clinically diagnosed group as in the newborn screening group, we showed that mean ($3,397,344) or median ($947,032) drug cost savings could have offset the estimated cost of adding cystic fibrosis to a UK national newborn screening service ($2,971,551). INTERPRETATION: Including indirect costs savings, newborn screening for cystic fibrosis might have even greater financial benefits to society than our estimate shows. Clinical, social, and now economic evidence suggests that universal newborn screening programmes for cystic fibrosis should be adopted internationally.

Cystic fibrosis diagnosed after 2 months of age leads to worse outcomes and requires more therapy.

OBJECTIVE: Newborn screening for cystic fibrosis remains controversial because improved pulmonary function has not been established. Studies to date have not accounted for differences in treatments delivered to clinically diagnosed children and newborn-screened controls. Here, we compare outcomes and treatment of patients clinically diagnosed within the newborn-screening reporting window (early-clinically diagnosed), those presenting after this period (late-clinically diagnosed), and patients diagnosed by newborn screening. PATIENTS AND METHODS: In a cross-sectional analysis of cohorts retrospectively ascertained, patients who were homozygous deltaF508 with cystic fibrosis, attending specialist cystic fibrosis centers, and 1 to 10 years of age between 2000 and 2002 were identified from the United Kingdom Cystic Fibrosis Database and stratified into newborn-screened, early-clinically diagnosed, or late-clinically diagnosed cohorts. Two analyses were performed: (1) after restricting to the most recent year of data collection, early-clinically diagnosed and late-clinically diagnosed cohorts were matched to newborn-screened patients by patient age and year of data collection (133 patients per cohort were identified); and (2) for all years of data collection, annual sets of data for early-clinically diagnosed and late-clinically diagnosed patients were matched to newborn-screened patients by patient age and year of data collection (291 data sets per cohort were identified). Median height and weight z scores, proportion of patients with height and weight <10th percentile, prevalence of chronic Pseudomonas aeruginosa infection, Shwachman-Kulczyki morbidity scores, percent predicted forced expiratory volume in 1 second, and numbers of long-term therapies were compared. RESULTS: In both analyses, newborn screening was associated with higher height z score, higher Shwachman-Kulczyki score, lower likelihood of height <10th percentile, and fewer long-term therapies compared with late-clinically diagnosed patients. No other differences were found. CONCLUSIONS: Newborn screening was associated with improved growth, reduced morbidity, and reduced therapy, yet generated equivalent pulmonary outcome compared with late clinical diagnosis, suggesting that newborn screening may slow cystic fibrosis lung disease progression.

Neonatal screening for cystic fibrosis is beneficial even in the context of modern treatment.

OBJECTIVES: To determine whether early identification of babies with cystic fibrosis (CF) improves outcome in the current environment of new improved treatments, considering the criticism that there may be only marginal benefit gained by CF newborn screening (NBS). STUDY DESIGN: We tested whether CF NBS in the setting of modern CF center care still afforded benefit using the UK CF Database (UKCFD; ) to compare clinical outcomes in infants who underwent NBS and control subjects who were clinically diagnosed (CD). With Mann-Whitney rank tests, 184 patients who underwent NBS aged 1 to 9 years in 2002 (excluding meconium ileus) were compared with matched patients who were CD in 3-year age groups (950 control subjects). RESULTS: Patients as old as 6 years who underwent NBS had significantly greater median height z-scores, less severe Northern chest radiography scores, better Shwachman-Kulczycki scores, and lower rates of chronic Pseudomonas aeruginosa infection. No difference was found for weight z-score or % predicted forced expiratory value in 1 second or forced volume capacity. Nutritional benefit was demonstrated in patients who underwent NBS and were homozygous for the DeltaF508 mutation. CONCLUSIONS: NBS segregates with better outcomes in patients as old as 6 years compared with age- and gene-matched control subjects who are CD. This cross-sectional study shows that infants who undergo screening derive nutritional benefit in improved median height and reduced morbidity.

Newborn screening for cystic fibrosis is associated with reduced treatment intensity.

OBJECTIVES: To determine whether the improved clinical status after newborn screening (NBS) for cystic fibrosis (CF) segregates with increased therapeutic intervention compared with presentation by clinical diagnosis (CD). STUDY DESIGN: In 2002, two populations (1 to 9 years of age) who presented (excluding meconium ileus) by NBS < or = 3 months of age or by CD were compared in an observational, cross-sectional design. NBS and CD populations (184 and 950 patients, respectively) were divided into 3-year age groups (1 to 3, 4 to 6, and 7 to 9 years). Therapies of duration >3 months were compared together with Pseudomonas aeruginosa infection status. RESULTS: NBS patients < or = 6 years of age received significantly fewer and less demanding therapies not explained by age, genotype, geography, or social deprivation. In 7- to 9-year-olds, significantly fewer NBS patients received intravenous antibiotics. NBS patients without P aeruginosa infection received significantly fewer therapies, but no differences were found between intermittently or chronically infected NBS and CD populations. Comparable results were found in deltaF508/deltaF508 subpopulations. CONCLUSIONS: CF populations diagnosed by NBS are associated with reduced treatment compared with age- and genotype-matched CD control subjects.

Comparative analysis of Cystic Fibrosis Registry data from the UK with USA, France and Australasia.

BACKGROUND: Using the UK Cystic Fibrosis Database, we analysed the health of the UK CF paediatric population (UKPP) in terms of their biographical, clinical and infection status and compared outcomes with the US, French and Australasian CF Registries. METHODS: UKPP data were collected for 2,673 patients aged less than 18 years in 2001 and used as a reference base for comparison with the most recent equivalent CF Registry reports. RESULTS: Although differences exist between National CF Registries, all record similar demographic factors and key outcomes. Where plausible comparisons can be made, we report that the UKPP had the oldest median age (15.0 years), the Australasian population had the lowest median age at diagnosis (1.8 months). Approximately, double the expected number of UKPP patients (23% and 19%, respectively) fall below the 10th centile for height and weight with similar outcomes in Australasia. UKPP and French populations had similar proportions with FEV1 >80% predicted (53% and 54%, respectively). CONCLUSION: Each Registry's data systems have developed independently providing a first step towards international comparisons. Standardisation of data collection criteria and definition for national CF Registries is required and we propose a standardised minimum data set, which would facilitate data integration as part of a global Registry for CF.

Demographics of the UK cystic fibrosis population: implications for neonatal screening.

The objective was to determine the composition of the Cystic Fibrosis (CF) Population attending specialist UK CF centres in terms of age, gender, age at diagnosis, genotype and ethnicity. With the planned introduction of the national CF screening programme in the UK, cystic fibrosis transmembrane regulator (CFTR) mutations were compared between different ethnic groups enabling a UK-specific frequency of mutations to be defined. Data were analysed from the patient biographies held in the UK CF Database (see www.cystic-fibrosis.org.uk). The currently registered population of 5,274 CF patients is 96.3% Caucasian with a male preponderance that significantly increases with age. The majority of the 196 non-Caucasian CF patients are from the Indian Subcontinent (ISC), of which one in 84 UK CF patients are of Pakistani origin. The commonest CFTR mutation, deltaF508, is found in 74.1% of all CF chromosomes. In the Caucasian CF population, 57.5% are deltaF508 homozygotes but the UK ISC CF population with only 24.7%, has significantly fewer deltaF508 homozygotes patients (95% confidence interval (CI) 0.2-0.4). The distribution of Caucasian patients with deltaF508/deltaF508, deltaF508/Other and Other/Other does not fit the expected distribution with a Hardy-Weinberg model unless those patients without a detected mutation are excluded (P<0.001). The UK CF Database has shown the UK CF population to have distinct characteristics separate from the North American and European CF Registries. The ISC group contains many mutations not recognised by current genetic analysis, and one in four ISC patients have no CFTR mutations identified. The CFTR analysis proposed for the screening programme would detect 96% of patients registered in the database, but is unlikely to achieve the desired >80% detection rates in the ethnic minority groups. Screen-positive, non-Caucasian infants without an identifiable CFTR mutation should be referred for a sweat test and genetic counselling when serum trypsinogen concentrations remain elevated after birth.