Disease foundations that are taking an increasing role in capital formation for local biotechs are nervously watching as the stock market and private capital markets wreak havoc with the companies that may hold the key to their future cures.

Originally posted in Journal of Cystic Fibrosis

We were interested to read recently in the Journal of ‘cepacia syndrome’ being successfully treated by combined nebulised and intravenous (IV) therapy with both meropenem and tobramycin in a 31 year old woman with cystic fibrosis (CF) and an en-bloc liver–pancreas transplant . This reminded us of one of our current patients who survived the ‘cepacia syndrome’ following treatment with IV antibiotics, nebulised tobramycin and recombinant human deoxyribonuclease (rhDNase) and remains relatively well 8 years later.

Originally posted in Journal of Cystic Fibrosis

Abstract: Early diagnosis and treatment of the respiratory and gastrointestinal complications of cystic fibrosis (CF) have led to improved survival with many patients living beyond the fourth decade. Along with this increased life expectancy is the risk of further disease associated with the chronic manifestations of their condition. We report a patient with documented CF related liver disease for which he was under routine surveillance that presented with histologically proven hepatocellular carcinoma (HCC). It is important that physicians are aware of this association as increased vigilance may lead to earlier diagnosis and perhaps, a better outcome.

Originally posted in Journal of Cystic Fibrosis

Abstract: Many countries have introduced newborn screening for cystic fibrosis to facilitate diagnosis prior to the development of lung disease. Although most infants with cystic fibrosis are asymptomatic from a respiratory point of view at diagnosis, structural lung disease has been detected by computed tomography. We present a case of an asymptomatic infant with cystic fibrosis diagnosed following newborn screening who had endobronchial infection with Pseudomonas aeruginosa and radiological evidence of bronchiectasis at 3 months of age.

Originally posted in Journal of Cystic Fibrosis

Abstract: Cystic fibrosis (CF; MIM# 219700) is the most frequent recessive disease in Caucasian patients. However, immigration from the Middle East and Africa to Europe is revealing different CFTR mutations.Here, we have described an 875+1G?A mutation, found for the first time in a homozygous state in an 8 yr old boy. He was the child of a couple of Egyptian first level cousins, both carriers of the mutation.The functional test revealed the 875+1G?A to be a severe mutation, leading to defective protein function as detected by nasal potential difference (NPD) measurements.

Originally posted in Journal of Cystic Fibrosis

Abstract: Mutation epidemiology in each ethnic group is important for cystic fibrosis diagnosis and genetic counselling. To date, little has been reported on the prevalence of cystic fibrosis in the Ecuadorian population where the mutation distribution appears to differ from that of Europe. We present a series of four Ecuadorian patients homozygous for the H609R mutation in the CFTR gene. This is the first report of detection of this mutation in the Ecuadorian population. Taking advantage of the homozygous status of the patients, an evaluation of the most important clinical parameters is presented. From the diagnostic point of view, the information provided by our study is of relevance in designing an appropriate strategy for genetic testing of patients in Ecuador and in European countries where immigration from Ecuador is common.

Originally posted in Journal of Cystic Fibrosis

Abstract: We investigated the prevalence of cystic fibrosis-related diabetes (CFRD) and its association with various demographic and clinical conditions in a Dutch child and adult cystic fibrosis (CF) population.Patients were classified as having either normal glucose tolerance (NGT), impaired glucose tolerance (IGT) or CFRD. Associations with the following parameters were studied: age, gender, BMI, mutations, pulmonary function, infection status, and hospitalization.In our patient population the prevalence of IGT and CFRD was 16% and 31% respectively. After excluding pancreatic sufficient patients, the prevalence of CFRD was 40% and in patients over 40 years 52%. Compared with patients with NGT, CFRD patients were older, had more in-hospital days and had worse pulmonary function. Women developed CFRD at a significantly younger age than men.CFRD is a frequently occurring co-morbidity in patients with CF. The prevalence of CFRD is increasing in ageing CF populations and deserves rising attention in CF management.

Originally posted in Journal of Cystic Fibrosis

Abstract: Introduction: Extra-pulmonary complications of Burkholderia cepacia complex (Bcc) infection in patients with cystic fibrosis are unusual. To the best of the authors’ knowledge no case of pyomyositis secondary to Bcc infection has been reported previously.Case presentation: We report a case of pyomyositis of the forearm caused by Bcc infection in a patient with CF. We also briefly discuss the management of pyomyositis.Conclusion: Pyomyositis is a potential extra-pulmonary complication of Bcc infection in patients with CF. A high index of clinical suspicion is required to make a prompt diagnosis. Final diagnosis may need MRI. An early diagnosis, aggressive medical therapy, multidisciplinary care and timely surgical intervention are all essential for proper management of this condition.

Originally posted in Journal of Cystic Fibrosis

Abstract: Approximately 10–80% of patients with Cystic Fibrosis (CF) have vitamin D deficiency. Obtaining therapeutic vitamin D levels has been a challenge for CF care providers using current recommended high-dose oral ergocalciferol (400,000 IU over 2 months). The objective of this study was to evaluate the safety and efficacy of a 2-week, very high dose ergocalciferol (700,000 IU over 14 days) repletion strategy in children and young adults with CF.As part of a quality improvement initiative, a prospective cohort study was performed from January through May 2007. Phase I included identifying individuals with CF who were subtherapeutic in 25-OH D. In phase II, 50,000 IU of ergocalciferol was prescribed for a 14 day term and administered daily. During phase III, a post treatment 25-OH D level was obtained to determine improvement. Baseline demographics and clinical characteristics were obtained at study entry. Stratification of the post 25-OHD levels was defined.Eighteen individuals with CF participated in the study. The mean age was 17±5 years (range 6–25 years). One hundred percent were pancreatic insufficient and required pancreatic enzyme replacement. All 18 had 25-OHD levels less than 30 ng/mL pre-treatment.Seventeen of the 18 (94%) participants became therapeutic in the 2-week interval. No patients had values considered high abnormal (100–150 ng/mL) or toxic (>150 ng/mL). Mean change was noted at an increase of 37.3±22 ng/mL in the 2-week period (p<0.001). Pre and peripubertal individuals had a significantly greater increase in 25-OH D levels.The results of this study demonstrate that very high dosing of vitamin D using oral ergocalciferol over a 14 day period is an effective strategy in achieving therapeutic levels of 25-OH vitamin D in children and young adults with CF. We believe this regimen deserves further study.

Originally posted in Journal of Cystic Fibrosis

Abstract: Background: Sexual and reproductive health (SRH) is increasingly relevant for men with CF. However, the extent of similarities or differences in SRH clinical practices across different centres or states is unknown as single clinic studies are not informative about variations in male preferences or clinical practices. We wished to determine the variability of male SRH knowledge and preferences, and clinical practices across different CF clinics.Methods: Men attending 5 adult CF clinics in Australasia completed a survey of SRH knowledge, attitudes and behaviours.Results: 264 (64%) men participated, with a median age of 30 years (17–56). 65% knew of near universal infertility due to a transport problem. 43% heard about infertility from their preferred source, but significantly later than desired. Less than half had undergone semen analysis (SA), which, while varying by site, was consistently later than preferred. 57 men were fathers, of whom 29 had utilised ART.Conclusion: Men’s preferences around SRH were more consistent than clinical practices. Clinical practice guidelines and training for health professionals would help reduce the gap between men’s SRH preferences and clinical practice.

Originally posted in Journal of Cystic Fibrosis

Abstract: Background: Adaptive aerosol delivery (AAD) nebuliser devices can reduce treatment times whilst enabling adherence to be monitored using inbuilt data logs. Using one such device, we have monitored nebulised antibiotic adherence in children with Cystic Fibrosis (CF).Methods: In CF children infected with Pseudomonas aeruginosa, downloaded data from an AAD device was used to calculate morning, evening and overall monthly adherence to antibiotic therapy over a year.Results: Overall monthly adherence to nebulised antibiotic therapy in 28 children was maintained between 60 and 70% over the year. Considerable variation in adherence, both between and within patients, was evident (Mean [SD] coefficient of variation, 37[44]%). Evening adherence (75[37]%) was better than morning adherence (58[34]%: p=0.012). Treatment regimens were changed in 8/28 patients based on adherence data.Conclusions: Routine adherence monitoring can be implemented in an outpatient setting. Using this type of information it is possible to identify which aspects of treatment can be improved and to work together with families to individualise treatments.

Originally posted in Journal of Cystic Fibrosis

Abstract: Background: Allergic bronchopulmonary aspergillosis (ABPA) in patients with CF is associated with frequent exacerbations and deterioration of lung function. Oral corticosteroids are standard therapy for ABPA and are associated with severe side effects. Monthly pulses of high-dose intravenous methylprednisolone (HDIVPM) are an effective therapy for autoimmune diseases with fewer side effects compared to oral prednisone, implicating its use for patients with CF who suffer from ABPA.Methods: 9 patients with CF and ABPA (4 male, 5 female, ages 7–36 years) received HDIVPM (10–15 mg/kg/d), for 3 days per month, and itraconazole, until clinical and laboratory resolution of ABPA.Results: All patients showed clinical and laboratory improvement (FEV1 increase, serum IgE levels and total eosinophil counts decrease) and treatment was discontinued after 6–10 pulses. Adverse effects were minor and disappeared shortly after each IV pulse therapy.Conclusion: High-dose IV-pulse methylprednisolone is an effective treatment for ABPA in CF with minor side effects.

Originally posted in Journal of Cystic Fibrosis

Abstract: Background: Cystic fibrosis (CF) specific patient-derived and reported symptom tools are critical steps toward evaluating the outcomes of new therapies for CF.Methods: We conducted 25 in-depth qualitative interviews using the Day Reconstruction Method and 9 cognitive interviews at two CF programs, the University of Washington and Seattle Children’s Hospital and Regional Medical Center. The interviews were audio-recorded and transcribed, and then coded and analyzed for themes relating to pulmonary symptoms and related psychosocial impacts.Results: Six pulmonary symptoms were identified as central to CF: cough, sputum production, wheeze, chest tightness, difficulty breathing/shortness of breath, and fever. Emotional impacts included frustration, sadness/depression, irritability, worry, difficulty sleeping; while activity impacts included time spent sitting or lying down, reduction of usual activities, and missing school or work. In all, 8 symptom items, 4 emotional impacts items, and 4 activity impacts were selected for inclusion on a new daily diary. We also assessed triggers for seeking care.Conclusions: Using a qualitative inductive methodology, we have obtained patient centered data regarding pulmonary symptoms and burdens and have created a novel patient reported outcome measure for CF. Future studies will assess the validity of the instruments.

Originally posted in Journal of Cystic Fibrosis

Abstract: Background: For the past decade, percentage of ideal body weight (%IBW) was recommended by European and US nutrition consensus reports as preferred clinical measure of nutritional status in children with cystic fibrosis (CF). We and others have demonstrated that the %IBW method underestimates the prevalence of nutritional failure in CF, but the underlying mechanism for this methodological flaw remains incompletely defined.Design: We performed model calculations from cross sectional growth data of healthy and CF-children to assess the methodological limitations of %IBW calculation.Results: Here we demonstrate that an intrinsic limitation of %IBW method is that it largely ignores the statistical principle of regression to the mean. The key assumption of %IBW is that ideal weight-for-age is on exactly the same percentile ranking as height-for-age. We show that this assumption is only valid if the individual’s height is close to the reference median. When the stature deviates from the median of the reference population, however, the increments of height-for-age and weight-for-age percentiles are not the same. In consequence, %IBW method systematically underestimates the ideal weight for smaller-than-average individuals, like CF-patients, which results in significant underestimation of the prevalence of malnutrition in this group of patients.Conclusion: There is increasing scientific evidence that calculation of %IBW as a measure of nutritional status in children with CF is flawed and should be discontinued. It is expected that future guidelines will recommend the use of alternative measures of weight-for-height proportion, e.g. BMI percentiles, to assess underweight and malnutrition in patients with CF.

Originally posted in Journal of Cystic Fibrosis

Abstract: Patient registries are organized systems of data collection for scientific, clinical or health strategy purposes.Aims of our review were to document scientific literature based on data and information from cystic fibrosis (CF) registries; to understand which clinical problems have been addressed and for which of these the studies concerned have correctly answered the questions raised (i.e. a methodological critique) and to identify clinical issues in need of further investigation. The review included primary studies starting from a formally constituted CF registry of at least national level, using data from the registry to evaluate research hypotheses.This article is an overview of the research undertaken, focusing in detail on the issues of mortality and survival. The studies considered here focused mainly or secondarily on survival in CF, the aim being to ascertain an improving trend, identify any prognostic factors and, in some cases, attempt to provide a predictive model of survival.

Originally posted in Journal of Cystic Fibrosis

Originally posted in Cystic Fibrosis News From Medical News Today

One-step screening for both genetic and chromosomal abnormalities has come a stage closer as scientists announced that an embryo test they have been developing has successfully screened cells taken from spare embryos that were known to have cystic fibrosis.

Originally posted in Cystic Fibrosis News From Medical News Today

Women with cystic fibrosis can have fertility treatment to help them have babies without any long-term adverse effects on either themselves or their children, according to new research presented at the 25th annual meeting of the European Society of Human Reproduction and Embryology in Amsterdam. Until relatively recently, cystic fibrosis (CF) was a death sentence and most people with the disease died by the time they reached their teenage years.

The Great Strides Walk is the Cystic Fibrosis Foundation’s largest national fundraising event.