Clinical characteristics and outcomes in adult cystic fibrosis patients with severe lung disease in Porto Alegre, southern Brazil

Background: Advanced lung disease in adult cystic fibrosis (CF) drives most clinical care requirements. The aim was to evaluate outcome (time to death while in the study) in a cohort of adult CF patients with severe lung disease, and to determine the association among baseline patient characteristics and outcome. Methods: A retrospective cohort study was performed and clinical records between 2000 and 2015 were reviewed. Severe lung disease was defined as forced expiratory volume in the first second (FEV1) < 30% of predicted. Outcomes of all patients, including their date of death or transplantation, were determined till January 1st, 2016. Clinical data were recorded at the entry date. Results: Among 39 subjects included in the study, 20 (51.3%) died, 16 (41.0%) underwent bilateral lung transplantation, and 3 were alive at the end of the study period. Two variables were independently associated with death: body mass index (BMI ≥ 18.5 kg/m2 ) (HR = 0.78, 95% CI = 0.64–0.96 and p = 0.017) and use of tobramycin inhalation therapy (HR = 3.82, 95% CI = 1.38–10.6 and p = 0.010). Median survival was 37 (95% CI = 16.4–57.6) months. The best cut-off point for BMI was 18.5 kg/m2 . Median survival in patients with BMI < 18.5 kg/m2 was 36 months (95% CI = 18.7–53.3). Conclusion: Median survival of CF subjects with FEV1 < 30% was 37 months. BMI and tobramycin inhalation therapy were independently associated with death. Median survival in patients with BMI < 18.5 kg/m2 was significantly lower than in patients with BMI ≥ 18.5 kg/m2 . The association of tobramycin inhalation with death was interpreted as confounding by severity (use was reserved for advanced lung disease)

A woman with cystic fibrosis, severe hypoxaemia, an atrial thrombus and a patent foramen ovale: a case report

<p>Abstract</p> <p>Introduction</p> <p>Cystic fibrosis is usually associated with chronic pulmonary sepsis and frequent infective exacerbations. We report a very unusual cause of severe hypoxaemia in a woman with cystic fibrosis caused by thrombus formation in the right atrium.</p> <p>Case presentation</p> <p>A 21-year-old Caucasian woman with cystic fibrosis and a totally implantable venous access device presented with severe hypoxaemia. This was initially treated with antibiotics but her oxygen levels did not improve significantly. Subsequently, a transient ischaemic attack occurred. Further investigations, including a contrast echocardiogram and a cardiac magnetic resonance scan, revealed the presence of a large right atrial thrombus and right-to-left intracardiac shunt through a patent foramen ovale.</p> <p>Conclusion</p> <p>This case highlights the need to consider a right-to-left shunt in chronic respiratory diseases when hypoxaemia is out of proportion to the degree of lung function impairment. Totally implantable venous access devices should always be considered as a source of thrombus formation.</p

ACTIVE: a randomised feasibility trial of a behavioural intervention to reduce fatigue in women undergoing radiotherapy for early breast cancer: study protocol

Background Fatigue is rated as the most distressing side effect of radiotherapy treatment for curable breast cancer. About four in ten women treated experience fatigue, which can last for years after treatment. The impact of this debilitating tiredness is loss of independence and impaired physical and mental function. Our study will take a behavioural intervention with demonstrated effect in treating fatigue in a mixed group of chemotherapy patients and adapt it for women undergoing radiotherapy for early breast cancer. The purpose of this trial is to evaluate the feasibility of delivering the intervention in the radiotherapy pathway for patients at a high risk of fatigue and to explore participants’ experiences of the trial and intervention. Methods A pragmatic single-site non-blinded feasibility trial of a behavioural intervention. Main inclusion criteria are prescription of the UK standard 40 Gy in 15 fractions over 3 weeks of radiotherapy (± tumour bed boost) for early (stage 0–IIIa) breast cancer. The total projected sample size after attrition is 70. A previously developed fatigue risk score tool will be used to predict individual’s likelihood of experiencing fatigue. Thirty women predicted to be at a high risk of experiencing significant fatigue will be allocated in the ratio 2:1 to the behavioural intervention or education trial arms, respectively. These feasibility trial participants will be assessed at baseline, after 10 and 15 fractions of radiotherapy and 10 days, 3 weeks and 6 months after radiotherapy. A further 40 women predicted to be at a lower risk of fatigue will join a risk score validation group. Measures to assess feasibility include recruitment, retention and completion rates and variation in implementation of the intervention. Process evaluation with intervention providers and users includes fidelity and adherence checks and qualitative interviews to understand how changes in behaviour are initiated and sustained. Discussion This feasibility study collates data to both inform the progression to and design of a future definitive trial and to refine the intervention

Burkholderia cepacia complex and limited cutaneous vasculitis in patients with cystic fibrosis : a case series

There is a high association of reactive skin presentations, mainly limited cutaneous vasculitis in patients with cystic fibrosis and Burkholderia cepcia complex chronic infection. This may be due to raised levels of circulating inflammatory mediators.Publisher PDFPeer reviewe

Emergence of methicillin resistance predates the clinical use of antibiotics

The discovery of antibiotics more than 80 years ago has led to considerable improvements in human and animal health. Although antibiotic resistance in environmental bacteria is ancient, resistance in human pathogens is thought to be a modern phenomenon that is driven by the clinical use of antibiotics1. Here we show that particular lineages of methicillin-resistant Staphylococcus aureus—a notorious human pathogen—appeared in European hedgehogs in the pre-antibiotic era. Subsequently, these lineages spread within the local hedgehog populations and between hedgehogs and secondary hosts, including livestock and humans. We also demonstrate that the hedgehog dermatophyte Trichophyton erinacei produces two β-lactam antibiotics that provide a natural selective environment in which methicillin-resistant S. aureus isolates have an advantage over susceptible isolates. Together, these results suggest that methicillin resistance emerged in the pre-antibiotic era as a co-evolutionary adaptation of S. aureus to the colonization of dermatophyte-infected hedgehogs. The evolution of clinically relevant antibiotic-resistance genes in wild animals and the connectivity of natural, agricultural and human ecosystems demonstrate that the use of a One Health approach is critical for our understanding and management of antibiotic resistance, which is one of the biggest threats to global health, food security and development

An international/multicentre report on patients with cystic fibrosis (CF) over the age of 40 years

AbstractBackgroundThe lifespan of patients with cystic fibrosis (CF) is increasing significantly. The objective of this international pilot study was to study the characteristics of these long-term survivors.MethodsFour centres with large CF clinics from London (UK), Minneapolis (USA), Toronto (Canada) and Verona (Italy) identified 366 patients who had survived 40years and longer.ResultsAt all centres males survived longer than females. There were more pancreatic sufficient patients in Verona (60%) and Toronto (40%) than in London (16%) and Minneapolis (21%). The percentage of ΔF508 homozygous patients varied between 47% in London and 45% in Minneapolis to only 26% in Toronto and 9% in Verona.Average FEV1 and BMI values of the surviving population appeared to stabilise after 40years of age. FEV1 was on average 12% higher in patients who were pancreatic sufficient (p > 0.0001). There was no difference in survival between the centres. The overall median survival after the age of 40 was 13years. The estimated annual death rate was approximately 3.4% from the age of 40–60years.ConclusionsSignificant numbers of patients are now surviving to 40years or more, and it is hoped that an in-depth study of these patients may identify the factors contributing to longer survival

Mediation of the total effect of cystic fibrosis‐related diabetes on mortality: A UK Cystic Fibrosis Registry cohort study

Abstract: Aim: To investigate whether the effect of cystic fibrosis‐related diabetes (CFRD) on the composite outcome of mortality or transplant could act through lung function, pulmonary exacerbations and/or nutritional status. Methods: A retrospective cohort of adult cystic fibrosis (CF) patients who had not been diagnosed with CFRD were identified from the UK Cystic Fibrosis Registry (n = 2750). Rate of death or transplant was compared between patients who did and did not develop CFRD (with insulin use) during follow‐up using Poisson regression, separately by sex. Causal mediation methods were used to investigate whether lung function, pulmonary exacerbations and nutritional status lie on the causal pathway between insulin‐treated CFRD and mortality/transplant. Results: At all ages, the mortality/transplant rate was higher in both men and women diagnosed with CFRD. Pulmonary exacerbations were the strongest mediator of the effect of CFRD on mortality/transplant, with an estimated 15% [95% CI: 7%, 28%] of the effect at 2 years post‐CFRD diagnosis attributed to exacerbations, growing to 24% [95% CI: 9%, 46%] at 4 years post‐diagnosis. Neither lung function nor nutritional status were found to be significant mediators of this effect. Estimates were similar but with wider confidence intervals in a cohort that additionally included people with CFRD but not using insulin. Conclusion: There is evidence that pulmonary exacerbations mediate the effect of CFRD on mortality but, as they are estimated to mediate less than one‐quarter of the total effect, the mechanism through which CFRD influences survival may involve other factors

The wheat Phs-A1 pre-harvest sprouting resistance locus delays the rate of seed dormancy loss and maps 0.3 cM distal to the PM19 genes in UK germplasm

The precocious germination of cereal grains before harvest, also known as pre-harvest sprouting, is an important source of yield and quality loss in cereal production. Pre-harvest sprouting is a complex grain defect and is becoming an increasing challenge due to changing climate patterns. Resistance to sprouting is multi-genic, although a significant proportion of the sprouting variation in modern wheat cultivars is controlled by a few major quantitative trait loci, including Phs-A1 in chromosome arm 4AL. Despite its importance, little is known about the physiological basis and the gene(s) underlying this important locus. In this study, we characterized Phs-A1 and show that it confers resistance to sprouting damage by affecting the rate of dormancy loss during dry seed after-ripening. We show Phs-A1 to be effective even when seeds develop at low temperature (13 °C). Comparative analysis of syntenic Phs-A1 intervals in wheat and Brachypodium uncovered ten orthologous genes, including the Plasma Membrane 19 genes (PM19-A1 and PM19-A2) previously proposed as the main candidates for this locus. However, high-resolution fine-mapping in two bi-parental UK mapping populations delimited Phs-A1 to an interval 0.3 cM distal to the PM19 genes. This study suggests the possibility that more than one causal gene underlies this major pre-harvest sprouting locus. The information and resources reported in this study will help test this hypothesis across a wider set of germplasm and will be of importance for breeding more sprouting resilient wheat varieties

Treatment preference amongst people with cystic fibrosis: the importance of reducing treatment burden

BACKGROUND: There is a growing consensus that the perspective of the patient should be considered in the evaluation of novel interventions. RESEARCH QUESTION: What treatment outcomes matter to people with cystic fibrosis (CF), and what trade-offs would they make to realise these outcomes? STUDY DESIGN AND METHODS: Adults attending a specialist CF centre were invited to complete an online discrete choice experiment (DCE). The DCE required participants to evaluate hypothetical CF treatment profiles, defined by impact on lung function, pulmonary exacerbations, abdominal symptoms, life expectancy, quality of life, inhaled medicines usage, and physiotherapy requirement. Choice data were analysed using multinomial logit and latent class models. RESULTS: 103 people with CF completed the survey (median age 35 years (range 18-76); 52% female; mean ppFEV1 69% (SD 22)). On average, an improvement in life expectancy by 10 years or more had the greatest impact on treatment preference, followed by a 15% increase in lung function. However, it was shown that people would trade substantial reductions in these key outcomes to reduce treatment time or burden. Preference profiles were not uniform across the sample: three distinct subgroups were identified, each placing markedly different importance on the relative importance of both life expectancy and lung function compared to other attributes. INTERPRETATION: The relative importance of treatment burden to people with CF, compared to life expectancy and lung function suggests it should be routinely captured in clinical trials as an important secondary outcome measure. When considering the patient perspective, it is important that decision makers recognise that the values of people with CF are not homogenous