Search

Background Cystic fibrosis (CF) can be responsible for premature death in young adults, but few data exist on end-of-life care in CF patients. Methods All deaths that occurred in CF patients in France between 2007 and 2010 were identified using the French CF Registry and medical records were obtained from CF centres. Circumstances of death were determined by an independent Mortality Adjudication Committee using data contained in medical records. Results Of 256 deaths [129 without lung transplantation (LTX), 127 after LTX], 215 (84%) occurred in hospital and 151 (59%) occurred in intensive care units (ICUs). No difference in care setting at death was observed when comparing deaths occurring without LTX vs. after LTX (in hospital deaths: 80% vs. 88%, P = 0.09; ICU deaths: 53% vs. 65%, P = 0.08). Of 129 deaths occurring without transplantation, only 25 patients died when listed for lung transplantation. Among patients who died without LTX, palliative care was implemented in less than 30% of patients, mostly in patients with major contraindication to transplantation. Major difference in end-of-life care were observed in patients who died with the first year after LTX as compared to those who died more than one year after LTX: ICU deaths, 92% vs. 47%; invasive ventilation at the time of death, 90% vs. 41%; palliative care, 6% vs. 45%, respectively (all comparisons, P <0.0001). Conclusion Deaths in CF patients occurred mainly in hospital, most often in ICUs under mechanical ventilation, even in patients not listed for LTX. Palliative care was mostly applied to patients with contraindication to LTX and to patients who died of late complications after LTX. [ABSTRACT FROM AUTHOR]

Background A study conducted at Cochin Hospital in Paris showed that PICC lines were generally safe to infuse IV antibiotic courses at home for patients with Cystic Fibrosis (CF) and non-CF bronchiectasis (Burgel et al., 2014). However, in our CF centre, we have observed that dressing changes performed by free-lance nurses are oftentimes inadequate and inconsistent. In France, PICC lines have been used since 2005 and home care is provided by free-lance nurses who are responsible for their own training on PICC line care. Objectives To evaluate the skills and practice of free-lance nurses relating to PICC line care, particularly to identify the variables leading to improper PICC line dressing change. Methods A survey was conducted among free-lance nurses between March 2012 and January 2014. 296 self-administered questionnaires were filled by nurses at the beginning of IV therapy training sessions. Results 56.4% had already used a PICC line. 91.6% of them had changed the dressing at least once, 74.4% of which had changed the sutureless securement device (SSD) at least once (41.2% of the overall population). 41% found the SSD difficult to remove and to set up. 43.4% had been trained by private medical supply providers and 39.7% by hospital personnel. Nurses who had been trained were four times more likely to answer questions correctly and three times more likely to have the skills to follow practice guidelines. Conclusion This study enabled us to gain a better understanding of home care nursing practice, and to identify SSDs change as the main problem and therefore to tailor IV therapy training to the actual needs of free-lance nurses working in the home care setting. [ABSTRACT FROM AUTHOR]

Background: Phase 3 trials have demonstrated the safety and efficacy of lumacaftor-ivacaftor (LUMA-IVA) in patients with cystic fibrosis (CF) homozygous for the Phe508del CFTR mutation and percent predicted forced expiratory volume in 1 s (ppFEV 1 ) between 40 and 90. Marketing authorizations have been granted for patients at all levels of ppFEV 1 ., Methods: To evaluate the safety and effectiveness of LUMA-IVA over the first year of treatment in patients with ppFEV 1 <40 or ppFEV 1 ≥90 in comparison with those with ppFEV 1 [40-90[. Analysis of data collected during a real world study, which included all patients aged ≥12 years who started LUMA-IVA in 2016 across all 47 French CF centers., Results: 827 patients were classified into 3 subgroups according to ppFEV 1 at treatment initiation (ppFEV 1 <40, n = 121; ppFEV 1 [40-90[, n = 609; ppFEV 1 ≥90, n = 97). Treatment discontinuation rate was higher in ppFEV 1 <40 patients (28.9%) than in those with ppFEV 1 [40-90[(16.4%) or ppFEV 1 ≥90 (17.5%). In patients with uninterrupted treatment, significant increase in ppFEV 1 occurred in the ppFEV 1 [40-90[subgroup (+2.9%, P<0.001), and in those ppFEV 1 <40 (+0.5%, P = 0.03) but not in those with ppFEV 1 ≥90 (P = 0.46). Compared with the year prior to initiation, the number of days of intravenous antibiotics were reduced in all subgroups, although 72% of patients with ppFEV 1 <40 still experienced at least one exacerbation/year under LUMA-IVA. Comparable increase in body mass index was seen in the three subgroups., Conclusion: Phe508del homozygous CF patients benefit from LUMA-IVA at all levels of baseline lung function , but the characteristics and magnitude of the response vary depending on ppFEV 1 at baseline., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest related to the work submitted for publication., (Copyright © 2020. Published by Elsevier B.V.)

Rationale: Lumacaftor-ivacaftor is a CFTR (cystic fibrosis transmembrane conductance regulator) modulator combination recently approved for patients with cystic fibrosis (CF) homozygous for the Phe508del mutation. Objectives: To evaluate the safety and effectiveness of lumacaftor-ivacaftor in adolescents (≥12 yr) and adults (≥18 yr) in a real-life postapproval setting. Methods: The study was conducted in the 47 CF reference centers in France. All patients who initiated lumacaftor-ivacaftor from January 1 to December 31, 2016, were eligible. Patients were evaluated for lumacaftor-ivacaftor safety and effectiveness over the first year of treatment following the French CF Learning Society's recommendations. Measurements and Main Results: Among the 845 patients (292 adolescents and 553 adults) who initiated lumacaftor-ivacaftor, 18.2% (154 patients) discontinued treatment, often owing to respiratory (48.1%, 74 patients) or nonrespiratory (27.9%, 43 patients) adverse events. In multivariable logistic regression, factors associated with increased rates of discontinuation included adult age group, percent predicted FEV 1 (ppFEV 1 ) less than 40%, and numbers of intravenous antibiotic courses during the year before lumacaftor-ivacaftor initiation. Patients with continuous exposure to lumacaftor-ivacaftor showed an absolute increase in ppFEV 1 (+3.67%), an increase in body mass index (+0.73 kg/m 2 ), and a decrease in intravenous antibiotic courses by 35%. Patients who discontinued treatment had significant decrease in ppFEV 1 , without improvement in body mass index or decrease in intravenous antibiotic courses. Conclusions: Lumacaftor-ivacaftor was associated with improvement in lung disease and nutritional status in patients who tolerated treatment. Adults who discontinued lumacaftor-ivacaftor, often owing to adverse events, were found at high risk of clinical deterioration.

Background: Ivacaftor has been shown to improve lung function and body weight in patients with CF and a gating mutation. Real-world evaluation is warranted to examine its safety and effectiveness over the long term., Methods: A retrospective observational multicentre study collected clinical data in the year before and the 2years after ivacaftor initiation in patients with CF and a Gly551Asp-CFTR mutation., Results: Fifty-seven patients were included. Mean absolute change in FEV 1 % predicted improved from baseline to Year 1 (8.4%; p<0.001) and Year 2 (7.2%; p=0.006). Statistically significant benefits were observed with increased body mass index, fewer Pseudomonas aeruginosa and Staphylococcus aureus positive cultures, and decreased IV antibiotics and maintenance treatment prescriptions (including azithromycin, Dornase alpha and nutritional supplements). No significant adverse events were reported., Conclusion: The clinical benefits of ivacaftor reported in previous clinical trials were confirmed in a real-world setting two years post-initiation, also reducing treatment burden., (Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the short-term adverse events and effectiveness of lumacaftor/ivacaftor combination treatment in adults with cystic fibrosis (CF) and severe lung disease in a real life setting., Methods: A multicentre observational study investigated adverse events, treatment discontinuation, FEV 1 and body mass index (BMI) one month and three months after lumacaftor/ivacaftor initiation in adults with CF and FEV 1 below 40% predicted., Results: Respiratory adverse events (AEs) were reported by 27 of 53 subjects (51%) and 16 (30%) discontinued treatment. The mean absolute change in FEV 1 was +2.06% after one month of treatment (P=0.086) and +3.19% after 3 months (P=0.009). BMI was unchanged., Conclusions: Treatment with lumacaftor/ivacaftor in patients with CF and severe lung disease was discontinued more frequently than reported in clinical trials, due to respiratory AEs. Nevertheless, the patients who continued treatment had an increase in lung function comparable to what was observed in pivotal trials., (Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Introduction: To define the characteristics of CF patients developing AA amyloidosis., Methods: A 30-year retrospective survey conducted within the national French CF network to identify cases of CF associated with AA amyloidosis., Results: Nine cases of AA amyloidosis were identified (CF prevalence in France is approximately 6000 patients) and sufficient data were collected in six. The clinical presentation was renal disease in four cases, a compressive goiter in one case, and epigastric pain in one case. Organ involvement included kidney disease in all cases (proteinuria, with a median age at onset of 24 years, 4 cases with nephrotic syndrome, 5 with renal failure); gastrointestinal (4 cases with duodenal ulcer); thyroid (2 cases); and hepatobiliary system (3 cases). The median age at diagnosis of CF was 6.5 years. Five patients had pancreatic insufficiency. All patients had chronic respiratory infections requiring intravenous antibiotics several times a year. Five patients have died, at a median age of 29 years and a median duration of 6 years after the onset of proteinuria., Conclusion: AA amyloidosis is a rare but morbid complication of CF. Renal involvement is predominant.

Biomass production in grasslands, a key component of food provision for domestic herbivores, is known to depend on climate, resource availability, and on the functional characteristics of communities. However, the combined effects of these different factors remain largely unknown. The aim of the present study was to unravel the causes of variations in the standing biomass of plant communities using a long-term experiment conducted in a Mediterranean rangeland of Southern France. Two management regimes, sheep grazing and grazing associated with mineral fertilization, were applied to different areas of the study site over the past 25 years. Abiotic (temperature, available water, nutrients) and biotic (components of the functional structure communities) factors were considered to explain interannual and spatial variations in standing biomass in these rangelands. Standing biomass was highly predictable, with the best model explaining -80% of variations in the amount of biomass produced, but the variation explained by abiotic and biotic factors was dependent on the season and on the management regime. Abiotic factors were found to have comparable effects in both management regimes: The amount of biomass produced in the spring was limited by cold temperatures, while it was limited by water availability and high temperatures in the summer. In the fertilized community, the progressive change in the functional structure of the communities had significant effects on the amount of biomass produced: the dominance of few productive species which were functionally close led to higher peak standing biomass in spring.

Objective: The long-term effects of protracted low level ionising radiation exposure are investigated in a combined analysis of French nuclear workers employed by the Commissariat à l'Energie Atomique (CEA), AREVA Nuclear Cycle (AREVA NC) and Electricité de France (EDF). Associations between cumulative external radiation dose and mortality due to solid cancers, leukaemia and circulatory disease were examined., Methods: All workers hired by CEA, AREVA NC and EDF between 1950 and 1994 who were employed for at least 1 year, badge-monitored for radiation exposure and alive on 1 January 1968 were included. Individual data of annual exposure to penetrating photons (X-rays and gamma rays) were reconstructed for each worker. Estimates of radiation dose-mortality associations were obtained using a linear excess relative risk (ERR) Poisson regression model., Results: Among the 59 021 nuclear workers, 2312 died of solid cancer, 78 of leukaemia and 1468 of circulatory diseases during the 1968-2004 period. Approximately 72% of the cohort had a non-zero cumulative radiation dose estimate, with a mean cumulative dose of 22.5 mSv. Positive but non-significant ERR/Sv were observed for all solid cancers, leukaemia excluding chronic lymphocytic leukaemia (CLL), ischaemic heart diseases and cerebrovascular diseases. A significant ERR/Sv was found for myeloid leukaemia., Conclusions: This is the first combined analysis of major French cohorts of nuclear workers. Results were consistent with risks estimated in other nuclear worker cohorts and illustrate the potential of a further joint international study to yield direct risk estimates in support to radiation protection standards.

Background & Aims: Increased life expectancy in patients with cystic fibrosis (CF) allows better knowledge of non-pulmonary complications like liver disease (CFLD). However, few data have been published in large adult cohorts. The aim of this study was to estimate the prevalence and the prognosis of CFLD in adult CF patients., Methods: A retrospective analysis of a monocentric cohort of adult CF patients prospectively followed, at least every year, was performed. CFLD was diagnosed using published composite criteria. If cirrhosis was suspected, upper digestive endoscopy was realized to assess the presence of portal hypertension., Results: A cohort of 285 adult CF patients was followed during 4.8 ± 3.6 years. Among them, 90 had CFLD at the beginning of follow-up and 23 a suspicion of cirrhosis. Factors independently associated with liver disease at baseline were history of meconium ileus, pancreatic insufficiency, chronic colonization with Burkholderia cepacia and the number of IV antibiotic courses per year. Nine patients developed liver decompensation during follow-up, all with a suspicion of cirrhosis at baseline. Six patients underwent liver transplantation alone and three patients combined liver and lung transplantation. Factors independently associated with death or lung transplantation at baseline were liver disease, BMI, forced expiratory volume in 1 second and number of IV antibiotic courses per year., Conclusions: CFLD was present at baseline in one third of adult patients with CF with a marked risk of liver decompensation during follow-up. Moreover, CFLD at baseline appears as an independent factor associated with death or lung transplantation., (Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Purpose: Epidemiological studies in nuclear industry workers can produce relevant information to better appreciate the health risks related to chronic external exposure to low doses of ionizing radiation (IR). This work examined the relations between exposure to IR and mortality in workers at the French Electricity Company (EDF), followed up to year 2003., Methods: Permanent staff who had worked for at least 1 year at EDF during period 1961-1994 and who had been monitored for exposure to IR were included (n = 22,393). One-sided trend tests for mortality according to cumulative dose and relative risks at 100 mSv were estimated using Poisson regression. Main analyses were stratified on age, sex, calendar time and education., Results: A total of 874 deaths occurred, and 66 workers were lost to follow-up. Median age at end of follow-up was 48. None of the causes of death investigated increased significantly according to dose, except cerebrovascular diseases (p = 0.01), but this last observation was based on only 22 cases., Conclusions: These results do not allow dismissing a possible influence of IR on cancer risk in this population. The cohort is still relatively young and therefore confidence intervals for estimated relative risks remain wide, although they have considerably narrowed since a previous analysis. Chance is a possible explanation for the association between IR and cerebrovascular mortality, due to the low number of cases on which it is based. These results thus need to be stabilized by conducting joint analyses with similar cohorts.

A total of 657 sputum samples from 201 cystic fibrosis adult patients were collected during a 24-month period (2005-2006). We retrospectively analyzed the fungal colonization of the respiratory tract of these individuals by linking medical records and microbiological data. Filamentous fungi were isolated from specimens of 65.6% of the patients, with Aspergillus fumigatus being the predominant species recovered as it was found in specimens of 56.7% of the patients. We observed no difference for gender, pancreatic status and cirrhosis in patients with or without A. fumigatus colonization. We found a higher percentage of recovery of Pseudomonas aeruginosa, Stenotrophomonas maltophilia and nontuberculous mycobacteria in patients with A. fumigatus colonization. During the follow-up period of the study, 8.9% of the patients were diagnosed with allergic bronchopulmonary aspergillosis (ABPA). By a multivariate analysis we demonstrated that Scedosporium apiospermum was significantly associated with ABPA (Odds ratio = 13 [2-80]) as opposed to A. fumigatus (Odds ratio = 1.58 [0.49-5.05]).

Background: We conducted a mortality study on a cohort of French nuclear workers employed at Electricité de France (EDF). A first cancer mortality analysis had covered the period 1968-1994. This paper presents results from a mortality analysis including nine additional years of follow-up to cover workers employed from 1968 to 2003., Methods: The cohort includes 22393 workers, 97% of whom are males. Employment data were updated using the EDF personnel file. Vital status was ascertained using the French National Registry of Population, and further completed using EDF personnel and pension files. Causes of death were obtained from the National registry of causes of death. Standardised Mortality Ratios (SMR) were computed using national rates as references. Variations of all causes and all cancers SMRs were studied according to demographic and occupational characteristics., Results: At the study end point (31/12/2003), 74% of workers are still in active employment. Only 0.3% of workers are lost to follow-up. The median duration of follow-up is 20 years. Causes are ascertained for 96% of deaths. The total number of deaths is 874, 307 of which are cancer deaths. SMRs for all causes and cancers show a significant deficit compared to the French national mortality. No significant excess was observed for any of the cancer sites studied. Non-significant excesses are observed for pancreatic, pleural, kidney and brain cancer. Significant variations of all causes SMRs according to age at study entry and attained age are observed. Significant variations of all causes and all cancers SMRs according to diploma at employment are observed, with a reduced SMR for a higher level of diploma., Conclusion: There is a significant deficit of mortality compared to the general population, reflecting a strong Healthy Worker Effect. Although nine years of follow-up were added, this cohort is made up of young workers, most of whom are still in active service. Regular updating of the follow up of this cohort is planned, aiming for an occupational health surveillance of workers occupationally exposed to ionizing radiation in France.

Background: Because more patients reach adulthood, new questions as "what about having a child and/or paternity responsibility?" arose., Method: We performed a retrospective investigation based on the French CF registry. The context of the paternity and the health status of fathers were recorded. A comparison with clinical status of non-father patients and a compilation of follow-up data to evaluate its impact were done., Results: Forty-eight men had 69 children. One fourth was said to be natural conceptions, 69% needed assisted reproduction techniques. No child had CF. Clinical status of men was satisfactory: mean BMI was 20.9 kg/m(2) and mean FEV(1) and FVC were 50.5% and 69.2% of predicted, respectively. When matched to CF non-fathers, few significant differences appeared. More non-fathers were F508del/F508del (p=0.03). Fathers' sputum cultures were positive for non-Pseudomonas aeruginosa strain (p=0.05), including Staphylococcus aureus (p=0.01). Mean age at diagnosis was higher, and based on minor evidence of sterility as first symptom leading to the diagnosis of CF (p=0.01) or aspergillosis (p=0.03). The 3-year follow-up showed no degradation of the clinical status., Conclusion: Men having paternity responsibility over children did not differ from the CF male population and neither did it seem to have an impact on the disease course.

Background: Intensive care unit (ICU) admission of adults with cystic fibrosis (CF) is controversial because of poor outcome. This appraisal needs re-evaluation following recent changes in both CF management and ICU daily practice. Objectives were to determine long-term outcome of adults with CF admitted in ICU and to identify prognostic factors., Methods: Retrospective multicenter study of 60 ICU hospitalizations for 42 adult CF patients admitted between 2000 and 2003. Reason for ICU admission, ventilatory support provided and one-year survival were recorded. Multiple logistic analysis was used to determine predictors of mortality., Results: Prior to ICU admission, all patients (mean age 28.1 +/- 8 yr) had a severe lung disease (mean FEV1 28 +/- 12% predicted; mean PaCO2 47 +/- 9 mmHg). Main reason for ICU hospitalization was pulmonary infective exacerbation (40/60). At admission, noninvasive ventilation was used in 57% of cases and was successful in 67% of patients. Endotracheal intubation was implemented in 19 episodes. Overall ICU mortality rate was 14%. One year after ICU discharge, 10 of the 28 survivors have been lung transplanted. Among recognized markers of CF disease severity, only the annual FEV1 loss was associated with a poor outcome (HR = 1.47 [1.18-1.85], p = 0.001). SAPSII (HR = 1.08 [1.03-1.12], p < 0.001) and endotracheal intubation (HR = 16.60 [4.35-63.34], p < 0.001) were identified as strong independent predictors of mortality., Conclusion: Despite advanced lung disease, adult patients with CF admitted in ICU have high survival rate. Endotracheal intubation is associated with a poor prognosis and should be used as the last alternative. Although efforts have to be made in selecting patients with CF likely to benefit from ICU resources, ICU admission of these patients should be considered.

Congenital bilateal absence of the vas deferens (CBAVD) with obstructive azoospermia is a congenital reproductive disorder that affects one in 10000 male individuals. The observation that many men presenting with CBAVD have mutations in their CFTR genes had led to the proposal that CBAVD may be a primary genital form of cystic fibrosis. We report here one novel mutation located in exon 10 of the CFTR gene. This mutation, named D513G (A-->G at position 1670), has been found in one of 83 patients with CBAVD from France, the analysis of exon 10 using a chemical clamp DGGE assay allowed us to identify three CF mutations AEF508 (37/166; 22%), AE1507 (1/166; 0/6%) and D513G (1/166; 0.6%), and two variants M470V and E528E (1716 G>A). The novel D513G mutation has not been found in more than 200 non-CF chromosomes and in a sample of 300 CF chromosomes from French classical CF patients.

Congenital bilateral absence of the vas deferens is a congenital reproductive disorder that affects about one in 1000 male individuals. Screening of the entire coding and flanking sequences of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 64 males with CBAVD revealed that in only 23% CBAVD was caused by two CFTR mutations. The 5T allele in one copy, that causes reduced levels of the normal CFTR protein, in combination with a CFTR mutation in the other copy, was one of the most common causes of CBAVD. Twenty six per cent of men with CBAVD had the 5T allele. The presence of only one CFTR mutation or the 5T allele in 34% of patients suggests that undetected changes in CFTR may be involved in CBAVD. These molecular defects are probably mutations with partial penetrance. Moreover, the high proportion (20%) of patients with CBAVD who did not have CFTR mutations or the 5T allele allows to propose that another gene or genes could be responsible for CBAVD. In these cases, in vitro fertilization may be required and the genetic counselling appears to be very complex and additional studies, including CFTR mRNA and linkage analyses, are required to resolve these questions.

The aim of our study is to compare lifetime risk estimates for radiation-induced breast cancer between various populations. Some epidemiological studies, mainly on Japanese A-bomb survivors, but also on North American populations irradiated for medical reasons, provide risk coefficients for excess mortality from breast cancer after exposure to ionizing radiation. For this comparative study, these risk coefficients have been transferred into the Japanese, American, and French populations, using demographic data, risk projection models, and assuming an individual acute exposure. The lifetime risk estimates are similar in the three populations when the additive projection model is used because of the similarity of the life tables of the three countries. However, using the multiplicative model, large differences appear due to the discrepancies in the baseline breast cancer rates between the Japanese and Occidental populations. It is for this reason that transfer of risk coefficients fitted on the Japanese population data must be considered with caution when applied to an Occidental population. Lifetime risk estimates for a given population, the French population for example, are largely dependent on the risk coefficients considered from various epidemiological studies. Nevertheless, for each source of data, they are higher with the multiplicative model than with the additive one. Moreover, it should be noted that data from medical irradiation lead to higher risk estimates when using the additive model, whereas studies of the A-bomb survivors lead to higher risk estimates with the multiplicative model. This comparative study points out the variations of the lifetime risk calculations according to the baseline breast cancer mortality rates of the three populations and with the use of different mathematical projection models.

A flock of 50 Lacaune ewes grazed three paddocks (approximately 17ha each) in rotation. Thirteen areas were defined in each of the two selected paddocks on the account of vegetation and spatial utilization by the ewes. These areas represented one tenth of the total area of the paddock. For each area the following measures were estimated: species of grasses, bushes, grass disponibility, amount of faeces deposited, infective larval population of strongyles, duration of the utilization by the ewes for resting or grazing. The measures were achieved during two rotational cycles from May to July 1981. Among the several methods utilized for the assessment of the various parameters influencing the probable infection of animals, one was unsatisfying (estimation of grass intake) and another was of particular good value (estimation of the amount of faeces deposited by an index method). The areas at risk were characterized by a vegetation with Bromus erectus associated either with Festuca duriuscula or Brachypodium pinnatum. The infectivity of each area (number of larvae X duration of grazing) was correlated to the number of strongyle eggs deposited, the amount of faeces accumulated and to an index of pasture quality (pastoral value X biomass of available grass). This work demonstrates that in heterogeneous pasture, even if the level of parasitism (Ostertagia sp. and Nematodirus sp.) is low, area at risk could be determined.