Perception, experience and relationship with food and eating in adults with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a multisystem disorder that primarily affects the respiratory and gastrointestinal systems. Dietetic therapy is a prominent aspect of CF management, with patients receiving nutritional surveillance and advice throughout their lifetime. The present study aimed to explore the perception, experience and relationship with food and eating in adults with CF. METHODS: Semi-structured telephone interviews were conducted with nine adults with CF. Interviews were audio-recorded, transcribed verbatim and analysed thematically following a previously described six-phase procedure. RESULTS: Six themes were identified: 'Sustained influence of eating experience in childhood', 'Eating for health: weight gain to prevent infection', 'Balancing health and body image', 'I'm different,' 'Strategies for managing food intake' and 'Support from family, friends and the CF Team'. Participants talked about the range of strategies they employ, with a focus on eating well and choosing high calorie foods being an important part of their health management strategy. This is driven by the belief that a good weight ensures better health and perceiving eating as a treatment. CONCLUSIONS: This group felt able to cope well and had developed strategies to manage their dietary needs. Food experience was variable throughout their lifetime, with childhood experience having a sustained effect on adult eating behaviour. Weight gain, body image and dietary health implications are considerable concerns for patients. New CF transmembrane modulator treatments (CFTR modulators) are changing the dietary needs of this population. It is important that these issues are explored during dietetic consultations to identify barriers to dietary change.

An exploration into experiences and attitudes regarding risky health behaviours in an adult cystic fibrosis population.

Health risk behaviours (HRBs) are prevalent within the cystic fibrosis (CF) population, and there is a lack of research around what influences their engagement. This research explored beliefs associated with HRBs within an adult CF population using qualitative semi-structured interviews. Participants' beliefs towards their CF and its life impact were investigated to explore reasons for engaging in HRB. A desire for normalcy was evident, often accompanied by engagement in everyday HRB as a method of minimising the illness identity. Evidence of a life-orientated illness perspective was also prevalent, with participants engaging in some risky behaviours for fun. Overall, there was a lack of knowledge on the consequences of HRB, with many participants reporting not being informed of these by clinicians. This research highlights a dilemma between clinical recommendations and personal life strategies undertaken by individuals with CF to support their identity.

Treatments for preventing recurrence of infection with Pseudomonas aeruginosa in people with cystic fibrosis.

BACKGROUND: Chronic infection with Pseudomonas aeruginosa (PA) in cystic fibrosis (CF) is a source of much morbidity and mortality. Eradication of early PA infection is possible, but can recur in many individuals. We sought to examine strategies to delay the time to PA recurrence in people with CF. OBJECTIVES: To establish whether secondary prevention strategies, using antibiotics or other therapies, increase the chances of people with CF remaining free from PA infection following successful eradication therapy. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched ongoing trials registries and the reference lists of relevant articles and reviews. Date of last search: 21 August 2019. SELECTION CRITERIA: Randomised controlled trials (and quasi-randomised trials where the risk of bias was low) comparing any treatment modality aimed at preventing recurrence of PA infection with placebo, standard therapy or any other treatment modality in people with CF who have undergone successful eradication of PA. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias. Quality of the evidence was assessed using GRADE. Conflicts were resolved by discussion and the opinion of a third review author was sought where necessary. Only a subset of participants in the included trial were eligible, therefore individual participant data were requested and obtained from the trial investigators. MAIN RESULTS: We included one trial (n = 306) in the review; however, only 253 participants had undergone successful eradication of PA, so fulfilling the inclusion criteria for our review. Information presented relates only to the included subset of participants. The trial recruited children aged one to 12 years (mean (standard deviation (SD)) age of 5.8 (3.5) years), 129 participants (51.0%) were female and the median follow-up was 494 days. We compared cycled therapy with tobramycin inhalation solution (TIS), in which participants underwent 28 days of TIS every three months, with culture-based therapy, in which participants were only prescribed medication when a quarterly sputum sample was positive for PA. Reasons for downgrading the quality of the evidence included applicability (only included children), incomplete outcome data and a small number of participants. The time to next isolation of PA was probably shorter with cycled TIS therapy than with culture-based therapy, hazard ratio (HR) 2.04 days (95% confidence interval (CI) 1.28 to 3.26) (moderate-quality evidence). This is in contrast to the main publication of the only included trial, which examined rate of PA positivity rather than time to PA infection and included participants not eligible for inclusion in this review. At the end of the trial, there was no difference between the cycled and culture-based groups in the change from baseline in forced expiratory volume in one second (FEV1) L, mean difference (MD) 0.0 L (95% CI -0.09 to 0.09) or in FEV1 % predicted, MD 0.70% (95% CI -4.33 to 5.73) (both very low-quality evidence). There was no difference in the change from baseline for FVC between the groups. There was also no difference in the frequency of pulmonary exacerbations between groups, MD -0.18 (95% CI -0.51 to 0.14) (moderate-quality evidence). Similarly, there was no difference between groups in the risk of participants developing novel resistant bacteria, RR 1.00 (95% CI 0.67 to 1.5) (moderate-quality evidence). There were more severe adverse events in the cycled group, but the type of treatment probably makes little or no difference to the results, RR 0.65 (95% CI 0.39 to 1.11) (moderate-quality evidence). There was no difference between groups in the change in weight or height from baseline or in rates of adherence to tobramycin or all trial medicines. The included trial did not assess changes in quality of life, the time to chronic infection with PA or the cost-effectiveness of treatment. AUTHORS' CONCLUSIONS: Cycled TIS therapy may be beneficial in prolonging the time to recurrence of PA after successful eradication, but further trials are required, specifically addressing this question and in both adults and children.

The top 10 research priorities in cystic fibrosis developed by a partnership between people with CF and healthcare providers.

There remain many treatment uncertainties in cystic fibrosis (CF). With limited resources, research should focus on questions which are most important to the CF community. We conducted a James Lind Alliance Priority Setting Partnership in CF. Research questions were elicited and then prioritised in successive surveys. A workshop agreed the final top 10. Online methods avoided cross infection and widened participation. The elicitation survey had 482 respondents (1080 questions) and prioritisation survey 677 respondents. Participants were drawn equally from the patient and clinical communities globally. We have achieved a consensus on 10 research priorities which will be attractive to funders.

A prospective pilot study of home monitoring in adults with cystic fibrosis (HOME-CF): protocol for a randomised controlled trial.

BACKGROUND: Home monitoring has the potential to detect early pulmonary exacerbations in people with cystic fibrosis (CF), with consequent improvements in health outcomes and healthcare associated costs. This study aims to assess the effects of home monitoring on hospital admissions, quality of life, antibiotic requirements, exacerbation frequency, lung function, nutritional outcomes, anxiety, depression, costs and health outcomes, as well as the qualitative effects on the patient experience. METHODS: This randomised controlled mixed-methods trial aims to recruit 100 adults with CF cared for in one large regional CF centre. Participants are randomly allocated 1:1 to the intervention group (twice-weekly home monitoring of symptoms measured by the Cystic Fibrosis Respiratory Symptom Diary - Chronic Respiratory Infection Symptom Score (CFRSD-CRISS) and Forced Expiratory Volume in one second (FEV1)) or a control group (routine clinical care) for the 12-month study period. Measurements are recorded at study visits at baseline, 3, 6, 9 and 12 months. Spirometry, body weight, co-morbidities, medications, hospital inpatient days, courses of antibiotics (oral and intravenous), pulmonary exacerbations (defined by the modified Fuchs criteria) are recorded at each study visit. Health status, capability and health economics are measured at each study visit by the Hospital Anxiety and Depression Scale (HADS), the ICEpop CAPability measure for Adults (ICECAP-A), EuroQol 5 dimensions (EQ-5D-5L) questionnaire and an adapted resource use questionnaire. The patient experience is assessed by semi-structured qualitative interviews at baseline and 12 months. DISCUSSION: Results from this study will help to determine the effect of home monitoring on inpatient bed days and quality of life in adults with CF, as well as other relevant health and health economic outcomes. TRIAL REGISTRATION: This study protocol is registered with Clinicaltrials.gov ( NCT02994706 ), date registered 16th July 2014.

Pseudomonas aeruginosa quorum sensing molecules correlate with clinical status in cystic fibrosis.

Pseudomonas aeruginosa produces quorum sensing signal molecules that are potential biomarkers for infection.A prospective study of 60 cystic fibrosis patients with chronic P. aeruginosa, who required intravenous antibiotics for pulmonary exacerbations, was undertaken. Clinical measurements and biological samples were obtained at the start and end of the treatment period. Additional data were available for 29 of these patients when they were clinically stable.Cross-sectionally, quorum sensing signal molecules were detectable in the sputum, plasma and urine of 86%, 75% and 83% patients, respectively. They were positively correlated between the three biofluids. Positive correlations were observed for most quorum sensing signal molecules in sputum, plasma and urine, with quantitative measures of pulmonary P. aeruginosa load at the start of a pulmonary exacerbation. Plasma concentrations of 2-nonyl-4-hydroxy-quinoline (NHQ) were significantly higher at the start of a pulmonary exacerbation compared to clinical stability (p<0.01). Following the administration of systemic antibiotics, plasma 2-heptyl-4-hydroxyquinoline (p=0.02) and NHQ concentrations (p<0.01) decreased significantly.In conclusion, quorum sensing signal molecules are detectable in cystic fibrosis patients with pulmonary P. aeruginosa infection and are positively correlated with quantitative measures of P. aeruginosa. NHQ correlates with clinical status and has potential as a novel biomarker for P. aeruginosa infection.

Nebulized and oral thiol derivatives for pulmonary disease in cystic fibrosis.

BACKGROUND: Cystic fibrosis is an inherited condition resulting in thickened, sticky respiratory secretions. Respiratory failure, due to recurrent pulmonary infection and inflammation, is the most common cause of mortality. Muco-active therapies (e.g. dornase alfa and nebulized hypertonic saline) may decrease sputum viscosity, increase airway clearance of sputum, reduce infection and inflammation and improve lung function. Thiol derivatives, either oral or nebulized, have shown benefit in other respiratory diseases. Their mode of action is likely to differ according to the route of administration. There are several thiol derivatives, and it is unclear which of these may be beneficial in cystic fibrosis. OBJECTIVES: To evaluate the efficacy and safety of nebulized and oral thiol derivatives in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches, hand searches of relevant journals, abstract books and conference proceedings.Most recent search: 13 June 2013.We also conducted a PubMed search on 26 February 2013 for relevant published articles. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing nebulized or oral thiol derivatives to placebo or another thiol derivative in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: The authors independently assessed trials for inclusion, analysed risk of bias and extracted data. MAIN RESULTS: Searches identified 23 trials; nine trials (255 participants) are included, of these seven trials are more than 10 years old. Three trials of nebulized thiol derivatives were identified (one compared 20% N-acetylcysteine to 2% N-acetylcysteine; another compared sodium-2-mercaptoethane sulphonate to 7% hypertonic saline; and another compared glutathione to 4% hypertonic saline). Although generally well-tolerated with no significant adverse effects, there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments.Six trials of oral thiol derivatives were identified. Three trials compared N-acetylcysteine to placebo; one compared N-acetylcysteine, ambroxol and placebo; one compared carbocysteine to ambroxol; and one compared low and high-dose N-acetylcysteine. Oral thiol derivatives were generally well-tolerated with no significant adverse effects, however there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments. AUTHORS' CONCLUSIONS: We found no evidence to recommend the use of either nebulized or oral thiol derivatives in people with cystic fibrosis. There are very few good quality trials investigating the effect of these medications in cystic fibrosis, and further research is required to investigate the potential role of these medications in improving the outcomes of people with cystic fibrosis.

A prospective randomised controlled mixed-methods pilot study of home monitoring in adults with cystic fibrosis.

BACKGROUND: Home monitoring (HM) is able to detect more pulmonary exacerbations (PEx) than routine care (RC) in individuals with cystic fibrosis (CF), but there is currently no evidence for benefits in health outcomes. Patient experiences of using HM and a health economics assessment have not been rigorously assessed to date. This study aimed to assess the effects of HM on hospital admissions, quality of life, antibiotic requirements, exacerbation frequency, lung function, nutritional outcomes, anxiety, depression, costs and health outcomes, as well as the qualitative effects on the patient experience. METHODS: This randomised controlled mixed-methods pilot study recruited CF adults cared for in one large regional CF centre. Participants were randomly allocated 1:1 to the intervention cohort [twice-weekly HM of symptoms measured by the Cystic Fibrosis Respiratory Symptom Diary - Chronic Respiratory Infection Symptom Score (CFRSD-CRISS) and forced expiratory volume in one second (FEV1)] or a control cohort (routine clinical care) for the 12-month study period. Measurements were recorded at study visits at baseline, 3, 6, 9 and 12 months. Spirometry, body weight, comorbidities, medications, hospital inpatient days, courses of antibiotics (oral and intravenous) and PEx (defined by the modified Fuchs criteria) were recorded at each study visit. Health status, capability and cost-effectiveness were measured at each study visit by the Hospital Anxiety and Depression Scale (HADS), the ICEpop CAPability measure for Adults (ICECAP-A), EuroQol 5 dimensions (EQ-5D-5L) questionnaire and an adapted resource use questionnaire. The patient experience of HM was assessed by semi-structured qualitative interviews at baseline and 12 months. RESULTS: Eighty-eight participants were recruited, with 44 (50%) randomised to receive HM and 44 (50%) randomised to receive RC. Patient hospital inpatient bed days per annum and overall health-related quality of life were similar between the groups. Protocol-defined PEx requiring intravenous and oral antibiotics were detected more frequently in the HM group, with no other differences between the groups in the secondary outcomes. The total mean National Health Service (NHS) costs were approximately £1500 more per patient for the RC arm than the HM group. The qualitative analysis demonstrated that the patient experience of HM was generally positive and overall the intervention was well accepted. CONCLUSION: The findings of this trial confirm that HM is effective in detecting PEx in adults with CF. There were no significant differences in hospital inpatient bed days and overall health-related quality of life between the groups. Despite the cost of the HM equipment and the salary of the research fellow to respond to the results, health economics analysis suggests the intervention was less expensive than RC. HM was generally well accepted, with most participants reporting that it resulted in them feeling more empowered and reassured. TRIAL REGISTRATION: The study protocol was registered with Clinicaltrials.gov (NCT02994706) on 16 July 2014 and published in a peer reviewed journal.Data from this trial has been presented in abstract form at the ECFS Conference in Lyon in September 2020.

Porphyromonas pasteri and Prevotella nanceiensis in the sputum microbiota are associated with increased decline in lung function in individuals with cystic fibrosis.

Although anaerobic bacteria exist in abundance in cystic fibrosis (CF) airways, their role in disease progression is poorly understood. We hypothesized that the presence and relative abundance of the most prevalent, live, anaerobic bacteria in sputum of adults with CF were associated with adverse clinical outcomes. This is the first study to prospectively investigate viable anaerobic bacteria present in the sputum microbiota and their relationship with long-term outcomes in adults with CF. We performed 16S rRNA analysis using a viability quantitative PCR technique on sputum samples obtained from a prospective cohort of 70 adults with CF and collected clinical data over an 8 year follow-up period. We examined the associations of the ten most abundant obligate anaerobic bacteria present in the sputum with annual rate of FEV1 change. The presence of Porphyromonas pasteri and Prevotella nanceiensis were associated with a greater annual rate of FEV1 change; -52.3 ml yr-1 (95 % CI-87.7;-16.9), -67.9 ml yr-1 (95 % CI-115.6;-20.1), respectively. Similarly, the relative abundance of these live organisms were associated with a greater annual rate of FEV1 decline of -3.7 ml yr-1 (95 % CI: -6.1 to -1.3, P=0.003) and -5.3 ml yr-1 (95 % CI: -8.7 to -1.9, P=0.002) for each log2 increment of abundance, respectively. The presence and relative abundance of certain anaerobes in the sputum of adults with CF are associated with a greater rate of long-term lung function decline. The pathogenicity of anaerobic bacteria in the CF airways should be confirmed with further longitudinal prospective studies with a larger cohort of participants.

Novel detection of specific bacterial quorum sensing molecules in saliva: Potential non-invasive biomarkers for pulmonary Pseudomonas aeruginosa in cystic fibrosis.

Pseudomonas aeruginosa produces specific signalling molecules, 2-alkyl-4-quinolones (AQs) that are detectable in the sputum of adults with cystic fibrosis (CF) and who have pulmonary infection with this opportunistic pathogen. This study aimed to determine whether AQs could be detected in saliva of patients with CF and known infection with Pseudomonas aeruginosa. Saliva and sputum samples were obtained from 89 adults with CF and analyzed using liquid chromatography-tandem mass spectrometry. AQs were detected in 39/89 (43.8%) saliva samples and 70/77(90.9%) sputum samples. Salivary AQs had a sensitivity of 50% (95%CI; 37.8; 62.2), specificity of 100% (95%CI; 47.8; 100), when compared to a molecular microbiological measure of P. aeruginosa in sputum as measured using polymerase chain reaction. Specific AQs produced by P. aeruginosa can be detected in the saliva and warrant investigation as potential non-invasive biomarkers of pulmonary P. aeruginosa.

Concerns regarding the safety of azithromycin in pregnancy - relevance for women with cystic fibrosis.

Chronic oral azithromycin therapy improves clinical outcomes in people with cystic fibrosis (CF), and is recommended for treatment of CF lung disease. Azithromycin is categorized as pregnancy class B. The data for risk of congenital malformations associated with use of azithromycin during pregnancy ranges from no risk to a small increased risk. As with other chronic medications used to treat CF, potential risk to the infant of use of azithromycin during pregnancy must be weighed against the potential risk to the mother of treatment discontinuation. Women with CF considering pregnancy while on chronic azithromycin should be counseled regarding potential risks and benefits.

2-Alkyl-4-quinolone quorum sensing molecules are biomarkers for culture-independent Pseudomonas aeruginosa burden in adults with cystic fibrosis.

Introduction. Pseudomonas aeruginosa produces quorum sensing signalling molecules including 2-alkyl-4-quinolones (AQs), which regulate virulence factor production in the cystic fibrosis (CF) airways.Hypothesis/Gap statement. Culture can lead to condition-dependent artefacts which may limit the potential insights and applications of AQs as minimally-invasive biomarkers of bacterial load.Aim. We aimed to use culture-independent methods to explore the correlations between AQ levels and live P. aeruginosa load in adults with CF.Methodology. Seventy-five sputum samples at clinical stability and 48 paired sputum samples obtained at the beginning and end of IV antibiotics for a pulmonary exacerbation in adults with CF were processed using a viable cell separation technique followed by quantitative P. aeruginosa polymerase chain reaction (qPCR). Live P. aeruginosa qPCR load was compared with the concentrations of three AQs (HHQ, NHQ and HQNO) detected in sputum, plasma and urine.Results. At clinical stability and the beginning of IV antibiotics for pulmonary exacerbation, HHQ, NHQ and HQNO measured in sputum, plasma and urine were consistently positively correlated with live P. aeruginosa qPCR load in sputum, compared to culture. Following systemic antibiotics live P. aeruginosa qPCR load decreased significantly (P<0.001) and was correlated with a reduction in plasma NHQ (plasma: r=0.463, P=0.003).Conclusion. In adults with CF, AQ concentrations correlated more strongly with live P. aeruginosa bacterial load measured by qPCR compared to traditional culture. Prospective studies are required to assess the potential of systemic AQs as biomarkers of P. aeruginosa bacterial burden.

Outcomes of pregnancy in women with cystic fibrosis (CF) taking CFTR modulators - an international survey.

BACKGROUND: As their long-term prognosis improves, women with CF are increasingly choosing to have children, but the safety of CFTR modulators in pregnancy and breastfeeding is currently unknown. METHODS: A survey was sent to lead clinicians of adult CF centres in Europe, the United Kingdom (UK), United States of America (USA), Australia and Israel requesting anonymised data on pregnancy outcomes in women using CFTR modulators before and during pregnancy and lactation. RESULTS: We identified 64 pregnancies in 61 women taking IVA (n = 31), LUM/IVA (n = 26) or TEZ/IVA (n = 7), resulting in 60 live births. In 44 pregnancies, CFTR modulators were either continued throughout pregnancy or temporarily stopped and then restarted. Two maternal complications were deemed related to CFTR modulator therapy; cessation of modulator therapy resulted in clinical decline in 9 women prompting resumption of therapy during pregnancy. No modulator-related complications were reported in infants exposed in utero and/or during breastfeeding. CONCLUSIONS: CFTR modulators were reported to be generally well tolerated in pregnancy and breastfeeding, with only 2 maternal complications that were deemed related to CFTR modulator therapy. Women stopping CFTR modulators in pregnancy may experience a decline in clinical status and in the cases identified in this survey, restarting therapy led to a clinical improvement. Current experience remains limited and longer-term prospective follow-up is required to exclude delayed adverse effects.

Characterising burden of treatment in cystic fibrosis to identify priority areas for clinical trials.

In a recent James Lind Alliance Priority Setting Partnership in cystic fibrosis (CF) the top priority clinical research question was: "What are effective ways of simplifying the treatment burden of people with CF?" We aimed to summarise the lived experience of treatment burden and suggest research themes aimed at reducing it. An online questionnaire was co-produced and responses subjected to quantitative and thematic analysis. 941 survey responses were received (641 from lay community). People with CF reported a median of 10 (interquartile range: 6-15) current treatments. Seven main themes relating to simplifying treatment burden were identified. Treatment burden is high, extending beyond time taken to perform routine daily treatments, with impact varying according to person-specific factors. Approaches to communication, support, evaluation of current treatments, service set-up, and treatment logistics (obtaining/administration) contribute to burden, offering scope for evaluation in clinical trials or service improvement.

Retinopathy and microalbuminuria are common microvascular complications in cystic fibrosis-related diabetes.

AIMS: To study the prevalence of microvascular complications and renal changes associated with cystic fibrosis-related diabetes (CFRD). METHODS: This retrospective cohort study was conducted at the West Midlands Adult Cystic Fibrosis centre, United Kingdom. Data regarding age, sex, microalbuminuria, retinopathy neuropathy, and biochemical results were collected for all people with CFRD who had an annual review from 1 January 2018 to 31 December 2018 at the centre. Descriptive statistics were analysed using STATAv15.1. RESULTS: A total of 189 patients were included, of which 56.6% were male and median age (interquartile range) was 33 (27-39) years; 79.4% (150/189) had their annual review in 2018. Those with a biochemically impaired renal function numbered 7.2% (13/180) and 22.7% (32/141) had microalbuminuria; 17.2% (10/58) had diabetes related retinopathy. No one in our cohort had diabetic ulcers; however, 10.3% (13/126) had absent foot pulses. CONCLUSION: We found a higher prevalence of microalbuminuria compared with retinopathy in a large cohort of cystic fibrosis adults. This study demonstrates the need for regular specialist follow-up to facilitate early identification of such complications and a long-term prospective cohort to understand underlying mechanisms.

Incidence of deep vein thrombosis associated with peripherally inserted central catheters in adults with cystic fibrosis.

PURPOSE: Peripherally inserted central catheters (PICCs) are commonly used in patients with cystic fibrosis (CF) to administer intravenous antibiotics for pulmonary exacerbations. The aim of this study was to determine the incidence of PICC-related deep vein thrombosis (DVT) in a large group of adults with CF with and without Burkholderia cepacia complex (BCC) infection, and to investigate the association between PICC-related DVT and preinsertion serum erythrocyte sedimentation rate (ESR). MATERIALS AND METHODS: This was a retrospective cohort study of all patients with PICCs inserted at a single institution during a 6-year period. A total of 524 adults with CF were treated in the clinic over this time period, with 147 (28.1%) having one or more PICCs inserted. Symptomatic venous thromboses were confirmed by Doppler ultrasound. Patients were classified as BCC-positive or BCC-negative, and preinsertion blood test results were analyzed. RESULTS: A total of 376 PICCs were inserted in 147 patients, with 12 patients (8.2%) developing symptomatic PICC-related DVT. Five additional subjects (3.4%) were diagnosed with asymptomatic PICC-related DVT. BCC-positive patients had a higher overall incidence of PICC-related DVT (20.9%) than BCC-negative patients (7.7%; P = .02). Preinsertion serum ESRs were higher in patients who subsequently developed PICC-related DVT (mean +/- SE, 54.4 mm/h +/- 7.2) compared with those without DVT (38.4 mm/h +/- 2.5; P < .05). CONCLUSIONS: The incidence of symptomatic PICC-related DVT was 3.7% per PICC. BCC-positive patients had a higher overall incidence of DVT than BCC-negative patients. Higher preinsertion ESRs in patients who developed PICC-related DVT suggest that systemic inflammation may be a risk factor for subsequent PICC-related DVT.

Nebulized and oral thiol derivatives for pulmonary disease in cystic fibrosis.

BACKGROUND: Cystic fibrosis is an inherited condition resulting in thickened, sticky respiratory secretions. Respiratory failure, due to recurrent pulmonary infection and inflammation, is the most common cause of mortality. Muco-active therapies (e.g. dornase alfa and nebulized hypertonic saline) may decrease sputum viscosity, increase airway clearance of sputum, reduce infection and inflammation and improve lung function. Thiol derivatives, either oral or nebulized, have shown benefit in other respiratory diseases. Their mode of action is likely to differ according to the route of administration. There are several thiol derivatives, and it is unclear which of these may be beneficial in cystic fibrosis. OBJECTIVES: To evaluate the efficacy and safety of nebulized and oral thiol derivatives in people with cystic fibrosis. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches, hand searches of relevant journals, abstract books and conference proceedings.Most recent search: November 2008. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing nebulized or oral thiol derivatives to placebo or another thiol derivative in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: The authors independently assessed trials for inclusion, analysed methodological quality and extracted data. MAIN RESULTS: Searches identified 18 trials; eight (seven older than 10 years) (234 participants) are included. Three trials of nebulized thiol derivatives were identified (one compared 20% n-acetylcysteine to 2% n-acetylcysteine; another compared sodium-2-mercaptoethane sulphonate to 7% hypertonic saline; and another compared glutathione to 4% hypertonic saline). Although generally well-tolerated with no significant adverse effects, there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments.Five studies of oral thiol derivatives were identified. Three studies compared n-acetylcysteine to placebo; one compared n-acetylcysteine, ambroxol and placebo; and one compared carbocysteine to ambroxol. Oral thiol derivatives were generally well-tolerated with no significant adverse effects, however there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments. AUTHORS' CONCLUSIONS: We found no evidence to recommend the use of either nebulized or oral thiol derivatives in people with cystic fibrosis. There are very few good quality trials investigating the effect of these medications in cystic fibrosis, and further research is required to investigate the potential role of these medications in improving the outcomes of people with cystic fibrosis.

Clinical significance of Pseudomonas aeruginosa 2-alkyl-4-quinolone quorum-sensing signal molecules for long-term outcomes in adults with cystic fibrosis.

Introduction. Pseudomonas aeruginosa is an important respiratory pathogen in cystic fibrosis (CF), which is associated with an accelerated decline in lung function, frequent pulmonary exacerbations and increased mortality. P. aeruginosa produces intercellular signalling molecules including 2-alkyl-4-quinolones (AQs), which regulate virulence-factor production and biofilm formation in the CF airways. Studies have shown that AQs are detectable in the sputum and plasma of adults with CF and chronic pulmonary P. aeruginosa.Aim. We tested the hypothesis that the presence of six AQs in plasma or sputum obtained from adults with CF was associated with long-term adverse clinical outcomes.Methodology. We analysed clinical data over an 8 year follow period for 90 people with CF who had previously provided samples for AQ analysis at clinical stability. The primary outcome was all cause mortality or lung transplantation. Secondary outcomes were the rate of lung-function decline and the number of intravenous (IV) antibiotic days for pulmonary exacerbations.Results. There was no statistical association between the presence of any of the six measured AQs and the primary outcomes or the secondary outcome of decline in lung function. One of the six AQs was associated with IV antibiotic usage. The presence of 2-nonyl-3-hydroxy-4(1 h)-quinolone (C9-PQS) in sputum was associated with an increase in the number of IV antibiotic days in the follow-up period (Mann-Whitney; P=0.011).Conclusion. Further investigation to confirm the hypothesis that C9-PQS may be associated with increased antibiotic usage for pulmonary exacerbations is warranted as AQ-dependent signalling is a potential future target for anti-virulence therapies.

Improving the care of patients with cystic fibrosis (CF).

BACKGROUND: The West Midlands Adult Cystic Fibrosis (CF) Centre based at Birmingham Heartlands Hospital provides care for adults with CF in the West Midlands. People with CF are prone to pulmonary exacerbations, which often require inpatient admission for intravenous antibiotics. We observed that the admission process was efficient during working hours (9:00-17:00, Monday-Friday) when the CF team are routinely available, but out-of-working hours, there were delays in these patients being clerked and receiving their first antibiotic dose. We were concerned that this was resulting in quality and potential safety issues by causing delays in starting treatment and prolonging hospital inpatient stays. We therefore undertook a quality improvement project (QIP) aimed at addressing these issues. An initial survey showed median time to clerk of 5 hours, with 60% of patients missing their first dose of antibiotics and mean length of stay of 16 days. METHODS: We applied the Plan-Do-Study-Act (PDSA) cycle approach, with the first PDSA cycle involving raising awareness of the issue through education to doctors, nurses and patients. RESULTS: This led to a reduction of median time to clerk from 5 to 2 hours with 23% of patients missing their first antibiotic dose and mean length of stay reducing to 14 days. The second cycle involved introducing an admissions checklist and displaying education posters around the hospital, resulting in median time to clerk remaining at 2 hours but only 20% of patients missing their first antibiotic dose and the mean length of stay remaining at 14 days. CONCLUSION: This QIP has improved the out-of-hours admissions process for adults with CF in our centre. We plan to review the longer term effects of the project including sustainability, effects on clinical outcomes and patient satisfaction.