Hebe B. Quinton

A regional intervention to improve the hospital mortality associated with coronary artery bypass graft surgery. The Northern New England Cardiovascular Disease Study Group.

OBJECTIVE To determine whether an organized intervention including data feedback, training in continuous quality improvement techniques, and site visits to other medical centers could improve the hospital mortality rates associated with coronary artery bypass graft (CABG) surgery. DESIGN Regional intervention study. Patient demographic and historical data, body surface area, cardiac catheterization results, priority of surgery, comorbidity, and status at hospital discharge were collected on CABG patients in Northern New England between July 1, 1987, and July 31, 1993. SETTING This study included all 23 cardiothoracic surgeons practicing in Maine, New Hampshire, and Vermont during the study period. PATIENTS Data were collected on 15,095 consecutive patients undergoing isolated CABG procedures in Maine, New Hampshire and Vermont during the study period. INTERVENTIONS A three-component intervention aimed at reducing CABG mortality was fielded in 1990 and 1991. The interventions included feedback of outcome data, training in continuous quality improvement techniques, and site visits to other medical centers. MAIN OUTCOME MEASURE A comparison of the observed and expected hospital mortality rates during the postintervention period. RESULTS During the postintervention period, we observed the outcomes for 6488 consecutive cases of CABG surgery. There were 74 fewer deaths than would have been expected. This 24% reduction in the hospital mortality rate was statistically significant (P = .001). This reduction in mortality rate was relatively consistent across patient subgroups and was temporally associated with the interventions. CONCLUSION We conclude that a multi-institutional, regional model for the continuous improvement of surgical care is feasible and effective. This model may have applications in other settings.

Survival of patients with diabetes and multivessel coronary artery disease after surgical or percutaneous coronary revascularization: results of a large regional prospective study

OBJECTIVES We sought to assess survival among patients with diabetes and multivessel coronary artery disease (MVD) after percutaneous coronary intervention (PCI) and after coronary artery bypass grafting surgery (CABG). BACKGROUND The Bypass Angioplasty Revascularization Investigation (BARI) demonstrated that diabetics with MVD survive longer after initial CABG than after initial PCI. Other randomized trials or observational databases have not conclusively reproduced this result. METHODS A large, regional database was linked to the National Death Index to assess five-year mortality. Of 7,159 consecutive patients with diabetes who underwent coronary revascularization in northern New England during 1992 to 1996, 2,766 (38.6%) were similar to those randomized in the BARI trial. Percutaneous coronary intervention was the initial revascularization strategy in 736 patients and CABG in 2,030. Cox proportional hazards regression was used to calculate risk-adjusted hazard ratios (HR) and 95% confidence intervals (CI 95%). RESULTS Patients who underwent PCI were younger, had higher ejection fractions and less extensive coronary disease. After adjusting for differences in baseline clinical characteristics, patients with diabetes treated with PCI had significantly greater mortality relative to those undergoing CABG (HR = 1.49; CI 95%: 1.02 to 2.17; p = 0.037). Mortality risk tended to increase more among 1,251 patients with 3VD (HR = 2.02; CI 95%: 1.04 to 3.91; p = 0.038) than among 1,515 patients with 2VD (HR = 1.33; CI 95%: 0.84 to 2.1; p = 0.21). CONCLUSIONS In this analysis of a large regional contemporary database of patients with diabetes selected to be similar to those enrolled in the BARI trial, five-year mortality was significantly increased after initial PCI. This supports the BARI conclusion on initial revascularization of patients with diabetes and MVD.

Longevity of Patients With Cystic Fibrosis in 2000 to 2010 and Beyond: Survival Analysis of the Cystic Fibrosis Foundation Patient Registry

Context Cystic fibrosis (CF) is a life-shortening disease, but care has improved. An updated assessment of survival is important for patients and their families and to plan for the health care needs of an increasing number of patients with CF living to adulthood. Contribution The survival of patients with CF enrolled in a national registry increased between 2000 and 2010. Conservative estimates assuming no further improvements suggest that median survival of a patient born and diagnosed in 2010 would be about 39 years. Implication The prognosis of patients with CF has improved, and more of these patients can be expected to need adult care. The Editors Cystic fibrosis (CF) is a heritable, life-shortening disease in which dysfunction of the CF transmembrane conductance regulator (CFTR) epithelial chloride channel dehydrates secretions in the airways, the pancreatic ducts, and elsewhere in the body, causing progressive organ damage (1). In 1966, the Cystic Fibrosis Foundation Patient Registry (CFFPR) was established to track the natural history of the disease, the effect of treatments, and patient health status and to design clinical trials. Registry data have been used to describe survival in CF and the role of specific clinical features in outcomes (25). Approximately 30000 persons in the United States have CF (2), and slightly more than 26000 living persons were represented in the CFFPR in 2010. In the earliest years of the CFFPR, persons with CF did not live to attend elementary school (6). By 2010, almost half of the patients in the registry were aged 18 years or older (6, 7). Advances in pulmonary and nutritional therapies continue to extend the life span of patients with CF. Daily regimens include airway clearance therapy; inhaled mucoactive agents and antibiotics; and a high-calorie, high-fat diet (8, 9). Early identification and management of CF-related diabetes (CFRD) has also been emphasized as a standard of care (10). In addition, universal newborn screening for CF, which has been linked to overall improved health by enabling earlier initiation of treatment (11), was instituted in all 50 states by 2009. Of persons diagnosed in 2010, 57.5% were diagnosed by newborn screening compared with only 8.0% of those diagnosed in 2000 (12). As new therapies emerge and patients with CF live longer, estimating survival is essential to providing an accurate prognosis to parents of newly diagnosed infants. Understandably, parents of children diagnosed with the disease want to provide the best possible care for their child and seek to understand what their childs future will hold (13). Because adults with CF are increasingly apt to pursue life-defining activities, such as marriage, parenthood, higher education, and employment (7, 14), parents may also need to reassess their supportive roles, such as during the period of transition from pediatric to adult care (15). Updated survival estimates will also inform the medical needs of an expanding population of adults with CF (16, 17). Decades of exposure to aminoglycosides are likely to result in increased vestibular (18) and renal dysfunction (19) in the older CF patient population. The prevalence of microvascular complications from CFRD (microalbuminuria, peripheral neuropathy, and retinopathy) increases with the duration of CFRD and should therefore inform screening efforts in older adults (20). Clinicians must also remain vigilant for depression and anxiety (21) among aging patients with CF. Additional unanticipated complications may emerge as the CF patient population continues to age. Recent evaluations of survival in the United Kingdom suggest that children diagnosed with CF since 2000 can anticipate a median survival greater than 50 years (22). Our objective in this study was to characterize survival in the United States between 2000 and 2010 in order to project survival for children born and diagnosed with CF in 2010 and thereby improve the clarity of prognostic dialogue and inform adult care needs. Methods The CFFPR is an institutional review boardapproved observational study at 110 Cystic Fibrosis Foundationaccredited care centers, encompassing more than 260 adult, pediatric, and affiliate programs. Data on patients with CF who have provided consent are collected through a secure Web-based portal. Findings on clinical presentation (such as respiratory symptoms, failure to thrive, and positive newborn screening result confirmed as CF); age at diagnosis; and encounter-based measures of nutritional status, pulmonary function, respiratory cultures, prescribed therapies, and CF-related complications are collected. Our analyses used data from patients in the CFFPR between 1 January 2000 and 31 December 2010 with a confirmed diagnosis of CF based on genotype and phenotype (including sweat chloride, pulmonary function, pancreatic status, and respiratory microbiology) (23). We sought to describe survival between 2000 and 2010, with analysis of mortality according to age, age at diagnosis, gender, race or ethnicity, F508del mutation status, and calendar year, and to project survival of children born and diagnosed with CF in 2010. Statistical Analysis We assessed trends in mortality between 2000 and 2010 by using multivariable Cox proportional hazards models. Calendar year was included as a time-dependent covariate, both as a continuous variable to estimate the rate of change over the decade and as a categorical indicator variable to estimate the rate relative to the year 2000. The time scale in the Cox proportional hazards models was age, with left truncation at entry into the registry or the year 2000, whichever occurred later. We adjusted for gender, race or ethnicity, F508del mutation status, presence of symptoms at diagnosis, and age at diagnosis (24, 25) because these patient characteristics are known at diagnosis (time-independent), are not modifiable by clinical care, and have been shown to be important predictors of survival in CF (24, 25). Therefore, these factors will be most relevant to clinicians who are providing information on prognosis to parents of children with the disease. We adjusted for F508del mutation status because it is an important predictor of survival (26) and its distribution in the CFFPR decreased during the study period. Furthermore, the F508del mutation accounts for approximately 70% of abnormal CFTR alleles, and approximately half of persons with CF are homozygous for this mutation (27). We estimated absolute annual mortality as a function of age, gender, and F508del mutation status for the period from 2000 to 2010 by smoothing age-specific rates with a triangular kernel with a radius of 5 years. Further details on the Cox proportional hazards models, the smoothed estimate of mortality, and subgroup analyses can be found in Appendix 1. We projected survival of children born and diagnosed with CF in 2010 because most future diagnoses will be made early in life due to universal newborn screening. Diagnoses made beyond infancy will probably be in persons with residual CFTR function and a milder phenotype. We present overall results and those stratified by gender and F508del mutation status using the mortality hazards estimated with data from 2000 to 2010 (additional information is provided in Appendix 2). We derived projections assuming that mortality does not change from the rate observed in 2010, mortality decreases at the same rate observed between 2000 and 2010 (1.8%), and mortality decreases at half the rate observed between 2000 and 2010 (0.9%). Institutional review board approval to conduct these analyses was obtained from the Dartmouth Committee for the Protection of Human Subjects. We used R, version 2.15.1, for the analyses, specifically the libraries survival and quantreg. Role of the Funding Source This project was funded by the Cystic Fibrosis Foundation. The funding source had no role in the design, conduct, or analysis of the study but provided access to the CFFPR data and contributed to the interpretation of the findings and the manuscript. Results Table 1 shows characteristics of all 34547 unique patients in the CFFPR from 2000 to 2010. Of these, we excluded patients with missing genotype data (11.9%) and those with missing data on gender, age at diagnosis, or age at entry into the registry (0.4%) from further analyses. Fewer than 4000 individuals (approximately 2.0% per year) were lost to follow-up, with no death date recorded. Between 2000 and 2010, the median age of the cohort increased from 14.3 to 16.7 years and the proportion of patients aged 18 years or older increased from 39% to 48%. Among newly diagnosed patients (that is, those with incident disease), the median age at diagnosis decreased from 6 months in 2000 to 1 month in 2010. The proportion of persons in the CFFPR who were homozygous for the F508del mutation decreased from 51% to 48%. Forty-two percent of patients entering the CFFPR in 2000 were homozygous for the F508del mutation compared with 36% of those entering in 2010. Table 1. Characteristics of Patients in the Cystic Fibrosis Foundation Patient Registry Mortality rate ratios from 2000 to 2010 with respect to calendar year, age at diagnosis, presentation at diagnosis, race or ethnicity, gender, and F508del mutation status are shown in Table 2. Mortality decreased with increasing age at diagnosis; for example, patients diagnosed between ages 5 and 9 years had a 21% (95% CI, 9% to 31%) lower adjusted risk for death than those diagnosed before age 1 year. Males had a 19% (CI, 13% to 24%) lower adjusted risk for death than females. Compared with patients who were homozygous for the F508del mutation, those with 1 copy of the mutation and those with no copies had a 14% (CI, 7% to 20%) and 25% (CI, 15% to 34%) lower adjusted risk for death, respectively. As reported in Table 2, the adjusted hazard ratio for the 10-year change in calendar year (2000 to 2010) was 0.83 (CI, 0.75 to 0.93), which equates to a 17%

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 models 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 patients preoperative risk of stroke.

Results of a regional study of modes of death associated with coronary artery bypass grafting

BACKGROUND It is well known that surgeon-specific in-hospital mortality rates for coronary artery bypass grafting vary, but this aggregate measure does not suggest specific opportunities for improvement. METHODS We performed a regional prospective study of 8,641 consecutive patients undergoing isolated coronary artery bypass grafting by all of the 23 cardiothoracic surgeons practicing in northern New England during the study period. Mode of death was assigned by an end points committee using predetermined definitions. Surgeons were ranked according to risk-adjusted mortality rates and grouped in terciles, and cause-specific mortality rates were determined. RESULTS The mortality rate was 3.3% in the lowest surgeon mortality tercile and 5.8% in the highest tercile. Fatal heart failure accounted for 80.0% of the difference in aggregate mortality rates, ranging from 1.9% in lowest surgeon mortality tercile to 4.0% in the highest tercile (p < 0.001). Rates of other causes did not differ significantly across surgeon mortality terciles. Differences in rates of fatal heart failure could not be explained by differences in preoperative left ventricular dysfunction or other patient characteristics. CONCLUSIONS Most of the difference in observed mortality rates across surgeons is attributable to differences in rates of heart failure.

The effect of peripheral vascular disease on in-hospital mortality rates with coronary artery bypass surgery

PURPOSE The purpose of this study was to examine the effect of peripheral vascular disease (PVD) on in-hospital mortality rates after coronary artery bypass grafting (CABG). METHODS We performed a regional cohort study of 3003 patients undergoing CABG between 1987 and 1989 at five tertiary care centers in Maine, New Hampshire, and Vermont. Data reflecting patient characteristics, severity of heart disease, comorbidity, and in-hospital mortality rates were collected prospectively; the presence of clinical and subclinical indicators of PVD was determined retrospectively. RESULTS Observed in-hospital mortality rates with CABG were 2.4-fold higher in the 796 patients with indicators of PVD (7.7%) than in the 2207 patients without PVD (3.2%) (crude odds ratio [OR] 2.42 [95% confidence interval (CI) 1.73-3.37]). After adjusting for their higher comorbidity scores, more advanced heart disease, and age, patients with PVD remained 73% more likely to die in hospital after CABG (adjusted OR 1.73 [CI 1.19-2.51]). The excess risk of in-hospital death associated with PVD was attributable largely to lower extremity occlusive disease (adjusted OR 2.03 [CI 1.34-3.07]). Subclinical lower extremity occlusive disease (asymptomatic absence of pedal pulses) had the same effect as clinically overt disease. Cerebrovascular disease had a small and statistically nonsignificant effect on CABG-related deaths (adjusted OR 1.13 [CI 0.73-1.74]). Excess mortality rates in patients with PVD were primarily due to increased risk of death from heart failure and dysrhythmias, but not to cerebrovascular accidents or peripheral arterial complications. CONCLUSIONS The presence of lower extremity arterial occlusive disease is an important, independent predictor of in-hospital mortality rates for patients undergoing CABG. Controlled studies of the long-term effects of CABG in patients with PVD are needed to determine the optimal role of myocardial revascularization in this population.

Improved in-hospital mortality in women undergoing coronary artery bypass grafting

BACKGROUND Few studies have examined the changes in in-hospital mortality for women over time. We describe the changing case mix and mortality for women undergoing coronary artery bypass grafting (CABG) from 1987 to 1997 in northern New England. METHODS Data were collected on 8,029 women and 21,139 men undergoing isolated CABG. The study consisted of three time periods (1987 to 1989, 1990 to 1992, and 1993 to 1997) to account for regional efforts to improve quality of care that occurred during 1990 to 1992. RESULTS Compared with 1987 to 1989, women undergoing CABG in 1993 to 1997 were older, had poorer ventricular function, and more often required urgent or emergency operations. The crude and adjusted mortality rates for both women and men decreased significantly over time. The absolute magnitude of the change in adjusted rates was greater for women (3.1%) than for men (1.5%). Although women represented only 28% of the study population, the decrease in their mortality accounted for 44% of the total decrease in adjusted mortality during the study period. CONCLUSIONS Over the last decade there has been a marked decrease in CABG mortality for women, despite a worsening case mix.

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.

Sensitivity of prevertebral soft tissue measurement at C3 for detection of cervical spine fractures and dislocations

A prevertebral soft tissue measurement exceeding 4 to 5 mm at C3 on a lateral spine radiograph is considered to be evidence of cervical spine injury. The objective of this study was to determine the sensitivity of the prevertebral soft tissue measurement at C3 in patients with proven cervical spine fractures or dislocations and to determine if this measurement correlates with the location or mechanism of injury. Consecutive patients 16 years of age or older who were admitted from July 1988 to June 1995 to a tertiary referral hospital with a discharge diagnosis of cervical spine fracture or dislocation were retrospectively studied. Patients were excluded if an interpretable lateral cervical radiograph taken within 24 hours of the injury was unavailable, medical records were unavailable or incomplete, the injury was caused by penetrating trauma or attempted hanging, or retropharyngeal air was present on the lateral radiograph. For each study patient, the earliest available lateral radiograph was obtained, and the prevertebral soft tissue measurement at the inferior aspect of C3 was recorded. All medical records and reports of imaging studies were reviewed. Two hundred thirty-two patients were identified and 21 were excluded, leaving 212 study patients. Injuries were classified as high (C1 to C2), low (C3 to C7), anterior, or posterior. For each patient the mechanism of injury was inferred from the fracture pattern according to established criteria. For all patients the sensitivity of a prevertebral soft tissue measurement at C3 of > 4 mm was 66% (95% confidence interval [CI] 59, 72). For C1 to C2 (n = 71) and C3 to C7 (n = 138) injuries, the sensitivities were 64% (95% CI 56, 78) and 64% (95% CI 56, 72), respectively. For anterior (n = 95) and posterior (n = 70) injuries the sensitivities were 64% (95% CI 54, 74) and 64% (95% CI 52, 75), respectively. There was no statistically significant difference in the prevertebral soft tissue measurement at C3 for high versus low injury, anterior versus posterior injury, or mechanism of injury. These results show that the prevertebral soft tissue measurement at C3 is an insensitive marker of cervical spine fracture or dislocation and does not correlate with the location or mechanism of injury.

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 models 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.