Altered Stool Microbiota of Infants with Cystic Fibrosis Shows a Reduction in Genera Associated with Immune Programming from Birth.

Previous work from our group indicated an association between the gastrointestinal microbiota of infants with cystic fibrosis (CF) and airway disease in this population. Here we report that stool microbiota of infants with CF demonstrates an altered but largely unchanging within-individual bacterial diversity (alpha diversity) over the first year of life, in contrast to the infants without CF (control cohort), which showed the expected increase in alpha diversity over the first year. The beta diversity, or between-sample diversity, of these two cohorts was significantly different over the first year of life and was statistically significantly associated with airway exacerbations, confirming our earlier findings. Compared with control infants, infants with CF had reduced levels of Bacteroides, a bacterial genus associated with immune modulation, as early as 6 weeks of life, and this significant reduction of Bacteroides spp. in the cohort with CF persisted over the entire first year of life. Only two other genera were significantly different across the first year of life: Roseburia was significantly reduced and Veillonella was significantly increased. Other genera showed differences between the two cohorts but only at selected time points. In vitro studies demonstrated that exposure of the apical face of polarized intestinal cell lines to Bacteroides species supernatants significantly reduced production of interleukin 8 (IL-8), suggesting a mechanism whereby changes in the intestinal microbiota could impact inflammation in CF. This work further establishes an association between gastrointestinal microbiota, inflammation, and airway disease in infants with CF and presents a potential opportunity for therapeutic interventions beginning in early life.IMPORTANCE There is growing evidence for a link between gastrointestinal bacterial communities and airway disease progression in CF. We demonstrate that infants with CF ≤1 year of age show a distinct stool microbiota versus that of control infants of a comparable age. We detected associations between the gut microbiome and airway exacerbation events in the cohort of infants with CF, and in vitro studies provided one possible mechanism for this observation. These data clarify that current therapeutics do not establish in infants with CF a gastrointestinal microbiota like that in healthy infants, and we suggest that interventions that direct the gastrointestinal microbiota closer to a healthy state may provide systemic benefits to these patients during a critical window of immune programming that might have implications for lifelong health.

New technologies and potential cost savings related to morbidity and mortality reduction in Class III/IV heart failure patients in Canada.

BACKGROUND: Heart failure affects 1-2% of the Canadian population. The 1-year mortality rates in New York Heart Association Class III/IV heart failure patients range from 11 to 44%. This study evaluates costs associated with current management of Class III/IV heart failure and potential savings if morbidity and mortality are reduced. OBJECTIVES: To construct an economic model to evaluate the components of treating Class III/IV heart failure patients in Canada and the resulting direct medical costs. The model also estimates the potential savings that could result from the introduction of a new technology such as cardiac resynchronization therapy that reduces morbidity and mortality. METHODS: The model evaluates costs of pharmacological therapy, medical care, laboratory and diagnostic tests, and complications, most commonly hospitalization. Estimates are based on a literature review, expert opinion, and standard cost sources using widely accepted health economic methods. RESULTS: The model, under conservative assumptions, estimates that Class III/IV heart failure costs between CAD$1.4 billion and CAD$2.3 billion in Canada overall. Costs are substantial on the provincial level as well and are estimated to be approximately CAD$700 million, CAD$500 million, and CAD$300 million in Ontario, Québec, and British Columbia, respectively. New treatments could bring substantial savings depending on their effectiveness-measured as reduction in morbidity and mortality-and the number of patients who receive that treatment. Potential savings in Canada could reduce the total annual costs for this group of patients by approximately 10% or up to CAD$200 million annually. CONCLUSIONS: The high level of morbidity and mortality in Class III/IV heart failure patients and costs associated with their care are an impetus for the development of new therapies such as cardiac resynchronization therapy, that could deliver long-term benefits including increased exercise tolerance, reduced hospitalizations, and improved quality of life. Successful therapies could provide substantial savings and present a favorable economic profile in the treatment of heart failure. In order to ensure that appropriate technologies are commercialized and marketed, prospective evaluation of new therapies should include critical assessment of direct medical costs in addition to evaluating morbidity, quality of life and survival.

Newborn hearing screening: costs of establishing a program.

OBJECTIVE: To evaluate the costs and performance characteristics associated with the start-up phase of Universal Newborn Hearing Screening Programs, one utilizing automated auditory brainstem response (AABR) and the other using transient evoked otoacoustic emissions (TEOAE). STUDY DESIGN: Economic and performance data were collected at the initiation of both screening programs. Data were collected until 1500 newborn infants were screened or until a referral rate for further audiologic evaluation at hospital discharge of less than or equal to 5% was achieved. Data collected included screening pass/fail rates, referral rates and personnel, equipment, and supply utilization. Actual costs of personnel, equipment, and supplies were used. Statistical comparisons of proportions using z-statistic with the one-tailed test and an alpha of 0.01 were made. RESULTS: Screening in the AABR program was performed by neonatal nurses, whereas screening in the TEOAE program was performed by master's level audiologists. The average age at initial screen was 29 hours for TEOAE, and 9.5 hours for AABR. Eighty-four percent of infants was screened within 24 hours in the AABR program, in contrast to 35% in the TEOAE program. Throughout the duration of the study, the referral rate at hospital discharge remained approximately 15% for the TEOAE program. The AABR referral rate began at 8% and was less than 4% at the completion of the study. Pre-discharge total costs for initiating and establishing the programs were US$49,316 for TEOAE and US$47,553 for AABR. Cost per infant screened was US$32.23 and US$33.68, respectively. When post-discharge screening and diagnostic evaluation costs were included, the total cost per infant screened was US$58.07 for TEOAE and US$45.85 for AABR. CONCLUSION: AABR appears to be the preferred method for universal newborn hearing screening. AABR was associated with the lowest costs, achieved the lowest referral rates at hospital discharge, and had the quickest learning curve to achieve those rates.