Outcome of patients with cystic fibrosis colonized by Scedosporium and Lomentospora species: A longitudinal cohort study.

Scedosporium and Lomentospora species rank second among the filamentous fungi colonizing the airways of cystic fibrosis (CF) patients. These fungi could be responsible for allergic bronchopulmonary mycosis (ABPM) and bronchitis before lung transplantation and invasive infections after. However, their role in CF lung disease is debated. This study aimed to identify clinical or environmental factors associated with an airway colonization by Scedosporium/Lomentospora species in patients with CF over a period of 7 years. A longitudinal cohort study was conducted from 2008 to 2014 in the CF reference centre in Lyon, France, to compare the characteristics of patients with Scedosporium/Lomentospora colonized and non-colonized patients. During the study period, 283 patients completed the clinical and microbiological follow-up. The analysis revealed that a higher number and duration of hospitalizations, an increased number of courses of parenteral antibiotic therapy, a history of ABPA, and treatment by itraconazole were significantly associated with an airway colonization by Scedosporium/Lomentospora species. The rate of decline of forced expiratory volume in the first second was not statistically different between colonized and non-colonized patients. This study provides evidence that patients colonized by Scedosporium/Lomentospora species require more medical care than non-colonized patients. Additional care could be in part explained by the management of Scedosporium/Lomentospora-related diseases such as ABPM or bronchitis. However, we did not demonstrate a faster rate of decline of respiratory function or body mass index in colonized patients, suggesting, as previously reported, that colonization of the airways by these fungi does not play a significant role in the progression of CF disease.

This prospective study did not demonstrate a faster rate of decline of respiratory function or body mass index in cystic fibrosis (CF) patients colonized by Scedosporium/Lomentospora species compared to non-colonized patients, suggesting that these fungi do not play a significant role in the progression of CF disease.

Adenoma detection with blue-water infusion colonoscopy: a randomized trial.

Background and aims Colonoscopy is currently the reference method to detect colorectal neoplasia, yet some adenomas remain undetected. The water infusion technique and dying with indigo carmine has shown interesting results for reducing this miss rate. The aim of this study was to compare the adenoma detection rate (adenoma and adenocarcinoma; ADR) and the mean number of adenomas per patient (MAP) for blue-water infusion colonoscopy (BWIC) versus standard colonoscopy. Methods We performed a multicenter, randomized controlled trial in eight units, including patients with a validated indication for colonoscopy (symptoms, familial or personal history, fecal occult blood test positive). Consenting patients were randomized 1:1 to BWIC or standard colonoscopy. All colonoscopies were performed by experienced colonoscopists. All colonoscopy quality indicators were prospectively recorded. Results Among the 1065 patients included, colonoscopies were performed completely for 983 patients (514 men; mean age 59.1). The ADR was not significantly different between the groups; 40.4 % in the BWIC group versus 37.5 % in the standard colonoscopy group (odds ratio [OR] 1.13; 95 % confidence interval [CI] 0.87 - 1.48; P = 0.35). MAP was significantly greater in the BWIC group (0.79) than in the standard colonoscopy group (0.64; P = 0.005). For advanced adenomas, the results were 50 (10.2 %) and 36 (7.3 %), respectively (P = 0.10). The cecal intubation rate was not different but the time to cecal intubation was significantly longer in BWIC group (9.9 versus 6.2 minutes; P < 0.001). Conclusion Despite the higher MAP with BWIC, the routine use of BWIC does not translate to a higher ADR. Whether increased detection ultimately results in a lower rate of interval carcinoma is not yet known. CLINICAL TRIALS REGISTRATION: EudraCT 2012-A00548 - 35; NCT01937429.

Pregnancy outcome in women with cystic fibrosis-related diabetes.

INTRODUCTION: With increasing life expectancy, more women with cystic fibrosis and diabetes mellitus become pregnant. We investigated how pre-gestational diabetes (cystic fibrosis-related diabetes) influenced pregnancy outcome and the clinical status of these women. MATERIAL AND METHODS: We analyzed all pregnancies reported to the French cystic fibrosis registry between 2001 and 2012, and compared forced expiratory volume (FEV1 ) and body mass index before and after pregnancy in women with and without pre-gestational diabetes having a first delivery. RESULTS: A total 249 women delivered 314 infants. Among these, 189 women had a first delivery and 29 of these had pre-gestational diabetes. There was a trend towards a higher rate of assisted conception among diabetic women (53.8%) than non-diabetic women (34.5%, p = 0.06), and the rate of cesarean section was significantly higher in diabetic women (48% vs. 21.4%, p = 0.005). The rate of preterm birth and mean infant birthweight did not differ significantly between diabetic and non-diabetic women. Forced expiratory volume before pregnancy was significantly lower in the diabetic group. The decline in forced expiratory volume and body mass index following pregnancy did not differ between the women with and those without pre-gestational diabetes. CONCLUSION: Pre-gestational diabetes in women with cystic fibrosis is associated with a higher rate of cesarean section but does not seem to have a clinically significant impact on fetal growth or preterm delivery. The changes in maternal pulmonary and nutritional status following pregnancy in women with cystic fibrosis were not influenced by pre-gestational diabetes.

Impact of a transition nurse program on the prevention of thirty-day hospital readmissions of elderly patients discharged from short-stay units: study protocol of the PROUST stepped-wedge cluster randomised trial.

BACKGROUND: In France, for patients aged 75 or older, it has been estimated that the hospital readmission rate within 30 days is 14 %, a quarter being avoidable. Some evidence suggests that interventions "bridging" the transition from hospital to home and involving a designated professional (usually nurses) are the most effective in reducing the risk of readmission, but the level of evidence of current studies is low. Our study aims to assess the impact of a care transition program from hospital to home for elderly admitted to short-stay units. METHODS: This is a multicentre, stepped-wedge cluster randomised trial. The program will be implemented at three times of the transition: 1) during the patient's stay in hospital: development of a discharge plan, creation of a transitional care file, and notification of the primary care physician about inpatient care and hospital discharge by the transition nurse; 2) on the day of discharge: meeting between the transition nurse and the patient to review the follow-up recommendations; and 3) for 4 weeks after discharge: follow-up by the transition nurse. The primary outcome is the 30-day unscheduled hospital readmission or emergency visit rate after the index hospital discharge. The patients enrolled will be aged 75 or older, hospitalized in an acute care geriatric unit, and at risk of hospital readmission or an emergency visit after returning home. In all, 630 patients will be included over a 14-month period. Data analysis will be blinded to allocation, but due to the nature of the intervention, physicians and patients will not be blinded. DISCUSSION: Our study makes it possible to evaluate the specific effect of a bridging intervention involving a designated professional intervening before, during, and after hospital discharge. The strengths of the study design are methodological and practical. It permits the estimation of the intervention effect using between- and within-cluster comparisons; the study of the fluctuations in unscheduled hospital readmission or emergency visit rates; the participation of all clusters in the intervention condition; the implementation of the intervention in each cluster successively. TRIAL REGISTRATION: This study has been registered as a cRCT at clinicaltrials.gov (identifier: NCT02421133 ). Registered 9 March 2015.

A Nurse-Led Bridging Program to Reduce 30-Day Readmissions of Older Patients Discharged From Acute Care Units.

OBJECTIVES: Older hospitalized patients are at high risk of early readmissions, requiring the implementation of enhanced coordinated transition programs on discharge. The objective of this study was to evaluate the impact of a nurse-led transition bridging program on the rate of unscheduled readmissions of older patients within 30 days from discharge from geriatric acute care units. DESIGN: A stepped-wedge cluster randomized trial. SETTING AND PARTICIPANTS: Seven hundred five patients aged ≥75 years hospitalized in one of 10 acute geriatric units, with at least 2 readmission risk-screening criteria (derived from the Triage Risk Screening Tool), were included from July 2015 to August 2016. METHODS: The intervention condition consisted in a nurse-led hospital-to-home bridging program with 4 weeks postdischarge follow-up (2 home visits and 2 telephone calls). Unscheduled hospital readmission or emergency department (ED) visits were compared in intervention and control condition within 30 days from discharge. RESULTS: The rate of 30-day readmission or ED visit was 15.5% in the intervention condition vs 17.6% in the control condition [hazard ratio stratified on clusters: 0.61 (upper limit unilateral 95% confidence interval = 1.11), P = .09]. Rate of presence of professional caregivers was increased in the intervention condition (P < .001). CONCLUSIONS AND IMPLICATIONS: Although the intervention resulted in an increase in the rate of implementation of a package of care at the 4-week of follow-up, we could not demonstrate a reduction in the rate of 30-day readmissions or ED visits of older patients at risk of readmission. These findings support the evaluation of this type of program on the longer term.

Quantifying Long-Term Changes in Lung Function and Exacerbations after Initiation of Azithromycin in Cystic Fibrosis.

Rationale: In cystic fibrosis, information on the efficacy of azithromycin past 12 months of treatment is still scarce.Objectives: The study sought to quantify the changes in lung function and the number of intravenous antibiotic courses (IVACs) after initiation of azithromycin in patients included in the French Cystic Fibrosis Registry.Methods: The study followed 1,065 children and 990 adults from 2 years before to 5 years after long-term azithromycin treatment initiated between 2001 and 2011. Mixed change-point models were used to quantify the changes in the forced expiratory volume (FEV) in 1 second and the yearly number of IVACs.Results: In the year of treatment initiation, the mean FEV was significantly higher than expected (+1.6%, P = 0.007 in children; +1.3%, P = 0.02 in adults). The decline of the FEV over time was less marked after than before treatment initiation (slope difference = +0.7% per year [P = 0.03] in children and +0.6% per year [P = 0.06] in adults). The mean increase in the yearly number of IVACs was lower after than before treatment initiation. The rate ratio quantifying the effect on the mean increase was 0.93 (95% confidence interval = [0.88-0.99]; P = 0.02) in children and 0.95 (95% confidence interval = [0.90-1.01]; P = 0.08) in adults.Conclusions: In children, long-term azithromycin treatment was associated with immediate and sustained beneficial changes in lung function and sustained beneficial changes in the frequency of pulmonary exacerbations. In adults, it was associated with immediate beneficial changes in lung function.

Pregnancy outcome in women with cystic fibrosis and poor pulmonary function.

BACKGROUND: To investigate how poor pre-gestational pulmonary function influenced pregnancy outcome and clinical status evolution in women with cystic fibrosis. METHODS: Pregnancies in women without lung transplantation with a first delivery reported to the French cystic fibrosis registry between 2000 and 2012 were identified. Pregnancy outcomes and clinical trends (body mass index - BMI, and pulmonary function) over a 4-year follow-up in women with poor pre-gestational pulmonary function, defined as forced expiratory volume (FEV1) ≤ 50%, were compared to those in women with FEV1 ˃ 50%. RESULTS: A total of 149 women had a first delivery and 36 (24.2%) of these had pre-gestational FEV1 ≤ 50%. There was no significant difference in age or frequency of assisted conception between the 2 groups. The rate of cesarean section was significantly higher in women with FEV1 ≤ 50% (43.7% vs. 21.1%, p = .01). The frequency of preterm birth did not differ significantly between the two groups, but median infant birthweight was significantly lower in women with FEV1 ≤ 50% (2705 g; range: 650-3700 vs. 3044 g; range: 1590-3860, p = .003). Despite significantly lower FEV1 and BMI the year before pregnancy for women with poor pulmonary function, the decline in these parameters during the study period did not differ significantly between the two groups. CONCLUSION: Poor pre-gestational pulmonary function in women with cystic fibrosis was associated with a higher rate of cesarean section and a clinically significant impact on fetal growth, but was not associated with more important pulmonary and nutritional decline over the study period.

Adherence to long-term therapies in cystic fibrosis: a French cross-sectional study linking prescribing, dispensing, and hospitalization data.

BACKGROUND: Cystic fibrosis (CF) is a life-shortening genetic condition that usually affects several organs and involves significant treatment burden. Adherence to medication is important for successful CF management. OBJECTIVE: To describe medication adherence according to age, therapeutic class, and pharmaceutical form in adults and children followed in four regional CF centers in France. METHODS: We conducted a cross-sectional study with non-transplanted patients followed in two adult and two pediatric centers during 2015 who were covered by the French National Health Insurance (NHI). Sociodemographic, clinical, hospitalization, and prescription data were collected from patient medical records. Medication dispensations were extracted from the regional French NHI database. Adherence was calculated over 12 months using continuous medication availability (CMA) accounting for dose adjustments and hospitalizations. Drug-specific CMA was computed in R with the AdhereR package for each medication prescribed more than 3 months, which was averaged to obtain a composite CMA score (cCMA) for all treatments and per therapeutic class as well as pharmaceutical form for each patient. RESULTS: A total of 228 patients were included. The number of chronic medications increased with age (r=0.50, p<0.001): a median of 7 medications per patient were prescribed. The mean±SD cCMA was significantly different between age groups (p=0.0098): it was 0.71±0.20 for the 0-5 years age group, 0.73±0.16 for 6-11 years, 0.64±0.17 for 12-17 years, 0.57±0.23 for 18-25 years, and 0.65±0.20 for the over 25 years age group. cCMA varied significantly according to pharmaceutical forms: the mean±SD cCMA was 0.70±0.21 for oral medications and 0.54±0.28 for inhaled medications (p<0.001). CONCLUSION: This study suggests that adherence to medication regimens in CF patients remains suboptimal and varies substantially between age groups and pharmaceutical forms. These variations in adherence should be considered when developing effective strategies to improve adherence.

Cystic fibrosis-related diabetes before lung transplantation is associated with lower survival but does not affect long-term renal function.

OBJECTIVE: To describe the prevalence of cystic fibrosis-related diabetes (CFRD) before and after lung transplantation (LT); to analyse the survival and renal function after LT according to the CFRD status before LT. METHODS: Sixty cystic fibrosis (CF) patients transplanted at the Lyon University Hospital between 2004 and 2014 were included. Genotype, pancreatic status, age at LT, survival were recorded. Glucose tolerance status, daily insulin dose requirement, glomerular filtration rate (GFR), and daily glucocorticoid (GC) dose were recorded before LT and until December 2016. RESULTS: The median follow-up was 5.6 (3.8-8.2) years, and nine patients died. Survival was poorest for patients with CFRD before LT compared with those without CFRD (P = 0.03) but was not correlated with the GFR before LT, with sex, age at LT, or CF genotype. The prevalence of CFRD was 68% at 2 years and 54% at 5 years. For persistent insulin-treated CFRD, the insulin requirement decreased (-2.1 IU/d/y; P < 0.01) and was correlated with the daily GC dose (+0.4 IU/d for one additional milligram, P = 0.012). Seven (11%) patients who had insulin-treated CFRD before LT became nondiabetic after LT, with a median time of 2 (1-4) years. After LT, the GFR decreased (-5.3 ml/min/1.73 m 2 /y; P < 0.001) and was not correlated with the CFRD status before LT. CONCLUSIONS: CFRD before LT is associated with poor survival after LT, which should lead to better management of diabetes. Some patients with pre-LT CFRD became nondiabetic after LT. CFRD is not associated with renal insufficiency after LT.

Glucose trajectories in cystic fibrosis and their association with pulmonary function.

BACKGROUND: The prevalence of cystic fibrosis-related diabetes is increasing. This condition is potentially responsible for respiratory decline. METHODS: At inclusion, then yearly (over three years), 111 children and 117 adults with cystic fibrosis had oral glucose tolerance and insulin tests at one (G1) and 2h (G2). KmL analysis identified homogeneous G1 and G2 glucose trajectories. A linear mixed model quantified the relationships between trajectories and FEV1 changes. RESULTS: In children, there were three G1 and four G2 trajectories and FEV1 decrease was not significantly different between G1 or G2 trajectories. In adults, two G1 and four G2 trajectories were identified and FEV1 change was estimated at -0.85/year (95% CI: [-1.54; -0.17], p=0.01) whatever the G1 trajectory and found significantly faster in the high and increasing G2 trajectory (-2.1/year, [-3.9; -0.2], p=0.03). CONCLUSIONS: In case of persistent G2 abnormality, physicians should be alert for clinical deterioration and intensify patient surveillance.