Children and young adults with CF in the USA have better lung function compared with the UK.

BACKGROUND: People with cystic fibrosis (CF) are managed differently in the USA and UK providing an opportunity to learn from differences in practice patterns. OBJECTIVES: To compare cross-sectional demographics, practice patterns and clinical outcomes between US and UK CF patients. METHODS: This was a cross-sectional study using 2010 data from patients in the US Cystic Fibrosis Foundation and the UK Cystic Fibrosis patient registries. The a priori outcome measures of interest were lung function and nutritional status. Descriptive statistics and two sample comparisons were performed. Stratification and multivariable linear regression were used to adjust for confounding. RESULTS: The study cohort included 13 777 children and 11 058 adults from the USA and 3968 children and 3965 adults from the UK. In children, mean body mass index centiles were similar. Lung function (FEV1 and FVC% predicted) was significantly higher in US patients ages 6-25 years of age. In a regression model adjusted for only age, FEV1% predicted was on average 3.31% of predicted (95% CI 2.65 to 3.96) higher in the USA compared with the UK. When adjusted for age, age at diagnosis, gender, pancreatic insufficiency and genotype, FEV1% predicted was on average 3.03% of predicted (95% CI 2.37 to 3.69) higher in the USA compared with the UK These differences persisted despite adjustment for possible confounders. Hypertonic saline and dornase alfa were much more commonly prescribed in US children. CONCLUSIONS: Children and young adults with CF have better lung function in the USA compared with the UK despite similar nutritional status.

Longevity of patients with cystic fibrosis in 2000 to 2010 and beyond: survival analysis of the Cystic Fibrosis Foundation patient registry.

BACKGROUND: Advances in treatments for cystic fibrosis (CF) continue to extend survival. An updated estimate of survival is needed for better prognostication and to anticipate evolving adult care needs. OBJECTIVE: To characterize trends in CF survival between 2000 and 2010 and to project survival for children born and diagnosed with the disease in 2010. DESIGN: Registry-based study. SETTING: 110 Cystic Fibrosis Foundation-accredited care centers in the United States. PATIENTS: All patients represented in the Cystic Fibrosis Foundation Patient Registry (CFFPR) between 2000 and 2010. MEASUREMENTS: Survival was modeled with respect to age, age at diagnosis, gender, race or ethnicity, F508del mutation status, and symptoms at diagnosis. RESULTS: Between 2000 and 2010, the number of patients in the CFFPR increased from 21,000 to 26,000, median age increased from 14.3 to 16.7 years, and adjusted mortality decreased by 1.8% per year (95% CI, 0.5% to 2.7%). Males had a 19% (CI, 13% to 24%) lower adjusted risk for death than females. Median survival of children born and diagnosed with CF in 2010 is projected to be 37 years (CI, 35 to 39 years) for females and 40 years (CI, 39 to 42 years) for males if mortality remains at 2010 levels and more than 50 years if mortality continues to decrease at the rate observed between 2000 and 2010. LIMITATIONS: The CFFPR does not include all patients with CF in the United States, and loss to follow-up and missing data were observed. Additional analyses to address these limitations suggest that the survival projections are conservative. CONCLUSION: Children born and diagnosed with CF in the United States in 2010 are expected to live longer than those born earlier. This has important implications for prognostic discussions and suggests that the health care system should anticipate greater numbers of adults with CF. PRIMARY FUNDING SOURCE: Cystic Fibrosis Foundation.

Key findings of the US Cystic Fibrosis Foundation's clinical practice benchmarking project.

Benchmarking is the process of using outcome data to identify high-performing centres and determine practices associated with their outstanding performance. The US Cystic Fibrosis Foundation (CFF) Patient Registry contains centre-specific outcomes data for all CFF-certified paediatric and adult cystic fibrosis (CF) care programmes in the USA. The CFF benchmarking project analysed these registry data, adjusting for differences in patient case mix known to influence outcomes, and identified the top-performing US paediatric and adult CF care programmes for pulmonary and nutritional outcomes. Separate multidisciplinary paediatric and adult benchmarking teams each visited 10 CF care programmes, five in the top quintile for pulmonary outcomes and five in the top quintile for nutritional outcomes. Key practice patterns and approaches present in both paediatric and adult programmes with outstanding clinical outcomes were identified and could be summarised as systems, attitudes, practices, patient/family empowerment and projects. These included: (1) the presence of strong leadership and a well-functioning care team working with a systematic approach to providing consistent care; (2) high expectations for outcomes among providers and families; (3) early and aggressive management of clinical declines, avoiding reliance on 'rescues'; and (4) patients/families that were engaged, empowered and well informed on disease management and its rationale. In summary, assessment of practice patterns at CF care centres with top-quintile pulmonary and nutritional outcomes provides insight into characteristic practices that may aid in optimising patient outcomes.

Validation and use of a parametric model for projecting cystic fibrosis survivorship beyond observed data: a birth cohort analysis.

BACKGROUND: The current lifetable approach to survival estimation is favoured by CF registries. Recognising the limitation of this approach, we examined the utility of a parametric survival model to project birth cohort survival estimates beyond the follow-up period, where short duration of follow-up meant median survival estimates were indeterminable. METHODS: Parametric models were fitted to observed survivorship data from the US CF Foundation (CFF) Patient Registry 1980-1994 birth cohort. Model-predicted median survival was estimated. The best fitting model was applied to a Cystic Fibrosis Registry of Ireland dataset to allow an evaluation of the model's ability to estimate predicted median survival. This involved a comparison of birth cohort lifetable predicted and observed (Kaplan-Meier) median survival estimates. RESULTS: A Weibull model with main effects of gender and birth cohort was developed using a US CFF dataset (n=13,115) for which median survival was not directly estimable. Birth cohort lifetable predicted median survival for male and female patients born between 1985 and 1994 and surviving their first birthday was 50.9 and 42.4 years respectively. To evaluate the accuracy of a Weibull model in predicting median survival, a model was developed for the 1980-1984 Cystic Fibrosis Registry of Ireland birth cohort (n=243), which had an observed (Kaplan-Meier) median survival of 27.7 years. Model-predicted median survival estimates were calculated using data censored at different follow-up periods. The estimates converged to the true value as length of follow-up increased. CONCLUSIONS: Accurate prognostic information that is clinically critical for care of patients affected by rare, life-limiting disorders can be provided by parametric survival models. Problems associated with short duration of follow-up for recent birth cohorts can be overcome using this approach, providing better opportunities to monitor survival and plan services locally.

The application of current lifetable methods to compare cystic fibrosis median survival internationally is limited.

BACKGROUND: Comparing international estimates of survival can be a useful way of highlighting differences in life expectancy between cystic fibrosis (CF) populations. In this study, we compared survival in two CF populations. METHODS: The current lifetable method takes age-specific mortality rates observed in a given year and applies them to a hypothetical population assuming those rates will remain the same in the future. This was used to compare median predicted survival in the United States (US) and the Republic of Ireland (RoI) (1986-2008). Median age at death among decedents was also examined. RESULTS: In both countries, median age at death was lower than median predicted survival. Successive increases in annual median predicted survival were not observed; rather an overall improvement was discerned over time. In the RoI, where absolute numbers of deaths were small, year-on-year fluctuations in age-specific mortality rates resulted in wide-ranging annual median predicted survival estimates. CONCLUSION: Median age at death is not a good measure of CF survival. Though median predicted survival improved in each country over the study period, between-country comparison at a given time point may be misleading for rare disorders like CF. Longitudinal outcomes must be examined.

Bacterial contamination of cystic fibrosis clinics.

BACKGROUND: Respiratory pathogens from CF patients can contaminate inpatient settings, which may be associated with increased risk of patient-to-patient transmission. Few data are available that assess the rate of bacterial contamination of outpatient settings. We determined the frequency of contamination of CF clinics and the effectiveness of alcohol-based disinfectants in reducing hand carriage of bacterial pathogens. METHODS: We conducted a point prevalence survey and before-after trial in outpatient clinics at 7 CF centers. The study examined CF patients with positive respiratory cultures for Pseudomonas, Staphylococcus, Stenotrophomonas or Burkholderia species. Hand carriage and environmental contamination with respiratory pathogens were assessed during clinic visits (Part I) and the effectiveness of hand hygiene performed by CF patients (Part II) was determined using molecular typing of recovered isolates. RESULTS: In Part I (n=97), the contamination rate was 13.6%. Pseudomonas and S. aureus, including methicillin-resistant strains, were cultured from patients' hands (7%), the exam room air (8%), and less commonly, environmental surfaces (1%). In Part II (n=100), the hand carriage rate of pathogens was 13.5% and 4 participants without initial detection of pathogens had hand contamination when recultured at the end of the clinic visit. CONCLUSIONS: Respiratory pathogens from CF patients can contaminate their hands and the clinic environment, but the actual risk of patient-to-patient transmission in the outpatient setting remains difficult to quantify. These findings support several recommendations CF infection control recommendations including hand hygiene for staff and patients, contact precautions for certain pathogens, and disinfecting equipment and surfaces touched by patients and staff.

Current issues in quality improvement in cystic fibrosis.

The modern history of cystic fibrosis (CF) is one of continuous improvement. Guidelines and evidence-based medicine provide a general roadmap for directing improvement efforts. Data and measurement are central to quality improvement (QI), a way of keeping score and staying on track. This article describes the history and context of QI in CF, the use of guidelines and data with some examples from the work of one regional consortium, some approaches to developing QI skills with a view to implementing and managing desired changes in CF clinic settings, and the potential benefits and impact of public reporting and data transparency.

Comparison of three measurements of cardiac surgery mortality for the Northern New England Cardiovascular Disease Study Group.

BACKGROUND: There is no consensus on the optimal period during which to assess death after coronary artery bypass graft (CABG) surgery. Three measures are commonly used: in-hospital, 30-day, and procedural (either in-hospital or 30-day) mortality. We used a regional database to calculate the CABG mortality rate using each of these mortality measures. METHODS: Data were collected prospectively on 31,592 consecutive isolated CABG surgeries in northern New England between January 1992 and December 2001. These data were linked to the National Death Index to obtain vital status through December 2001, and used to calculate 30-day and procedural mortality rates. Procedural mortality was defined as death occurring either within the hospital setting or within 30 days of the index procedure. Regional registry data were used to calculate in-hospital mortality rates. RESULTS: Mortality rates and their 95% confidence intervals were calculated. In all but one medical center, the in-hospital mortality was the lowest rate, while in all centers the procedural mortality rate was the highest. There were 1,082 deaths captured by the procedural mortality measure. Of these, 927 were included in the in-hospital mortality measure; 956 occurred within 30 days of surgery. CONCLUSIONS: Each of the measures studied has its advantages and may be used to assess the mortality outcomes of cardiac surgery. The more important issue other than the specific measure used is our ability to measure and validate it conveniently and accurately in actual practice.

Perioperative stroke and long-term survival after coronary bypass graft surgery.

BACKGROUND: Stroke is a devastating complication of coronary artery bypass graft (CABG) surgery. In-hospital outcomes have been described, yet the long-term effect of stroke on mortality following CABG surgery has not been well studied. METHODS: We examined the survival of 35,733 consecutive patients undergoing isolated CABG surgery in northern New England from 1992 through 2001. Stroke was defined as a new fixed neurologic defect that persisted at least 24 hours after surgery. Patient records were linked to the National Death Index to assess mortality. There were 147,931 person years of follow-up and 5,705 deaths. Cox proportional hazard regression was used to calculate the adjusted hazard ratios (HR) and 95% confidence intervals (95% CI). We identified the 5-year survival stratified by primary stroke mechanism, the patient's functional impact, and discharge location among a subset of patients who had strokes between 1992 and 2000. RESULTS: Perioperative stroke occurred in 575 patients (1.61%). Patients who had strokes had more comorbidities. After adjustments for differences in baseline patient and clinical characteristics, patients who had perioperative stroke were at a significantly increased risk for death (HR, 3.20; 95% CI, 2.80 to 3.66; p < 0.0001). Survival for patients with stroke at 1, 5, and 10 years was 83.0%, 58.7%, and 26.9%, respectively. Five-year survival decreased among patients who had major functional limitations before discharge, among those who had hypoperfusion strokes, and among patients who were discharged to locations other than home or rehabilitation facilities. CONCLUSIONS: Perioperative stroke is associated with a very substantial increased risk of postoperative death among CABG surgery patients. The greatest risk of death was noted within the first year after surgery. Survival after 1 year approximates that of patients who did not suffer a stroke.

Survival in patients with peripheral vascular disease after percutaneous coronary intervention and coronary artery bypass graft surgery.

BACKGROUND: Patients with peripheral vascular disease (PVD) undergoing coronary revascularization have high rates of adverse outcomes. Whether there are important differences in outcomes for surgical versus percutaneous coronary revascularization is unknown. The objective of this study was to compare survival in patients with PVD who underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) surgery for multivessel coronary artery disease. METHODS: In-hospital data were collected on 1,305 consecutive patients undergoing coronary revascularization (PCI, n = 341; CABG, n = 964) in northern New England from 1994 to 1996. Patient records were linked to the National Death Index to assess survival out to 3 years (mean 1.2 years). Logistic and Cox proportional hazards regression were used to calculate risk-adjusted odds ratios and hazard ratios. RESULTS: Compared with CABG patients, those undergoing PCI were more often women, had more renal failure, more prior coronary revascularizations, were more likely to have two-vessel coronary artery disease and were more likely to undergo the procedure emergently. They were less likely to have a history of heart failure. After adjusting for differences in baseline characteristics, patients undergoing CABG had better intermediate survival than did PCI patients (hazard ratio 0.68; 95% confidence interval, 0.46 to 1.00; p = 0.05). CONCLUSIONS: Patients with multivessel coronary artery disease and PVD undergoing CABG surgery have better intermediate survival out to 3 years than similar patients undergoing PCI. This information may be useful in counseling patients with PVD requiring coronary revascularization.

Development and validation of a prediction model for strokes after coronary artery bypass grafting.

BACKGROUND: A prospective study of patients undergoing coronary artery bypass graft surgery (CABG) was conducted to identify patient and disease factors related to the development of a perioperative stroke. A preoperative risk prediction model was developed and validated based on regionally collected data. METHODS: We performed a regional observational study of 33,062 consecutive patients undergoing isolated CABG surgery in northern New England between 1992 and 2001. The regional stroke rate was 1.61% (532 strokes). We developed a preoperative stroke risk prediction model using logistic regression analysis, and validated the model using bootstrap resampling techniques. We assessed the model's fit, discrimination, and stability. RESULTS: The final regression model included the following variables: age, gender, presence of diabetes, presence of vascular disease, renal failure or creatinine greater than or equal to 2 mg/dL, ejection fraction less than 40%, and urgent or emergency. The model significantly predicted (chi(2) [14 d.f.] = 258.72, p < 0.0001) the occurrence of stroke. The correlation between the observed and expected strokes was 0.99. The risk prediction model discriminated well, with an area under the relative operating characteristic curve of 0.70 (95% CI, 0.67 to 0.72). In addition, the model had acceptable internal validity and stability as seen by bootstrap techniques. CONCLUSIONS: We developed a robust risk prediction model for stroke using seven readily obtainable preoperative variables. The risk prediction model performs well, and enables a clinician to estimate rapidly and accurately a CABG patient's preoperative risk of stroke.

Median household income and mortality rate in cystic fibrosis.

CONTEXT: Poverty has been shown to be a determinant of health outcomes in many epidemiologic studies. OBJECTIVE: The goal of this study was to assess the association between household income and the mortality rate in cystic fibrosis (CF) patients. DESIGN, SETTING, AND PATIENTS: We selected white patients diagnosed before 18 years old and having 1 or more records in the Cystic Fibrosis Foundation Patient Registry since 1991. These 23 817 patients were linked to the 1990 US Census by their zip code of residence. The median household income was adjusted for state level differences in cost of living using the 1998 Consumer Price Index. INTERVENTIONS: None. MAIN OUTCOME MEASURES: We examined the association between categories of the median household income and the mortality rate. We examined the association between income categories and age-related changes in pulmonary function and body weight as well as specific nutritional and pulmonary therapies. RESULTS: We found a strong monotonic association between the median household income and the mortality rate. The test of trend was significant, and this effect was maintained after adjustment for a variety of patient and disease characteristics. When the lowest income category (<20 000 dollars) is compared with the highest (> or = 50 000 dollars), the adjusted incidence rates were 90.3 and 62.6 per 10 000 person years, respectively; this represents a 44% increased risk of death in the lowest income category. Patients living in areas with lower median household income also had consistently lower pulmonary function and body weight than did those living in higher income areas. The differences in weight percentiles and forced expiratory volume in 1 second are substantial in magnitude, they appear at an early age, and they persist into adulthood for these CF patients. Prescribed nutritional treatments and screening for CF-related diabetes were significantly higher among patients living in areas with lower median household income. Prescription of deoxyribonuclease and inhaled tobramycin was not significantly associated with median household income. CONCLUSION: There was a strong association between lower household income and increased mortality rate among CF patients. Additional understanding of this effect will require more complete and direct measurement of socioeconomic status and a better understanding of treatment adherence, local environmental conditions, and especially the care of CF patients during the early years of life.

Case-mix adjustment for evaluation of mortality in cystic fibrosis.

Comparison of patient mortality rates in cystic fibrosis (CF) obtained from different institutions requires the use of case-mix adjustment methods to account for baseline differences in patient and disease characteristics. There is no current professional consensus on the use of case-mix adjustment methods for use in comparing mortality rates in CF. Characteristics used for this case-mix adjustment should include those that are different across institutions and are associated with patient survival. They should not include characteristics of disease severity that may be a consequence of effectiveness of treatment. The goal of these analyses was to identify a set of these characteristics of patients or disease that would be useful for case-mix adjustment of CF mortality rates. Data from the Cystic Fibrosis Foundation Patient Registry and from the United States Census of the Population (1990) were used in these analyses. Kaplan-Meier techniques, the log-rank test, and Cox proportional hazards regression were used to estimate survivorship, calculate hazard ratios (HR), 95% confidence intervals (CI(95%)), and to conduct tests of statistical significance. The data set included all 30,469 CF patients seen at CF Care Centers from 1982-1998. There were 5,906 deaths during 508,721 person-years of follow-up. In multivariate analyses, female gender (HR 1.30, CI(95%) (1.16, 1,47), P < 0.001), nonwhite race (HR 1.48, CI(95%) (1.07, 2.04), P = 0.018), Hispanic ethnicity (HR 1.85, CI(95%) (1.42, 2.43), P < 0.001), and symptomatic presentation (respiratory, gastrointestinal, respiratory and gastrointestinal, meconium ileus, and other symptomatic presentations; HRs 1.38-1.83; P values, 0.028 to < 0.001) were associated with higher risk of death. The homozygous Delta F508 genotype (HR 1.36, CI(95%) (1.19, 1.55), P < 0.001) and neither mutation being Delta F508 (HR 1.40, CI(95%) (1.15, 1.71), P = 0.001) were also associated with higher risk of death. Patients diagnosed after 36 months of age had almost 50% reduction in risk of death compared to those diagnosed before 6 months of age (HR 0.52 CI(95%) (0.44, 0.61), P < 0.001). When patients living in zip codes with a median household income > $50,000/year (corrected for the 1999 consumer price index) were compared with those living in areas with a median household income < $20,000/year, it was apparent that those in the wealthier areas had a 40% reduced risk of death (HR 0.60, CI(95%) (0.44, 0.82), P = 0.001). All of these characteristics were independently significant predictors of death, and all of these characteristics differed significantly across the CF Care Centers. This case-mix adjustment model uses patient and disease characteristics available at the time of diagnosis of CF, and is not believed to be influenced by subsequent treatment to predict the risk of death. If these case-mix adjustment methods are adopted broadly, they will make it possible to study treatment effects and differences in mortality outcomes, while adjusting for baseline differences in patient and disease characteristics.