Predictors of pulmonary exacerbation treatment in cystic fibrosis.

J Cyst Fibros. 2019 Jun 27;:

Authors: Sanders DB, Ostrenga JS, Rosenfeld M, Fink AK, Schechter MS, Sawicki GS, Flume PA, Morgan WJ

Abstract
BACKGROUND: Most studies of pulmonary exacerbations (PEx) in cystic fibrosis (CF) focus on intravenous (IV)-treated PEx, though most PEx are treated with oral antibiotics. Our objectives were to describe predictors of antibiotic choice and outcomes for PEx initially identified in clinic.
METHODS: For each patient in the U.S. CF Foundation Patient Registry, we selected the first PEx recorded at a clinic visit in 2013-14 following a clinic visit without a PEx. We used multivariable logistic regression to determine associations between clinical characteristics and antibiotic treatment choice. We determined outcomes in the 90 days after the first PEx.
RESULTS: Among 14,265 patients with a PEx initially identified in clinic, 21.4% received no antibiotics, 61.5% received new oral and/or inhaled antibiotics, and 17.0% had IV antibiotics within 14 days. Compared to IV antibiotics, patients more likely to receive new oral and/or inhaled antibiotics: were male, <13 years old, had BMI >10th percentile or 18.5 kg/m2, >90 days between clinic visits, FEV1 > 70% predicted at the PEx, no prior-year IV-treated PEx, FEV1 decline <10% predicted, and private insurance. Following the PEx, 30.3% of patients had no clinical encounters within 90 days. Treatment with IV antibiotics within 90 days occurred for 23.7% treated without antibiotics, 22.8% of new oral and/or inhaled antibiotics, and 27.1% of IV antibiotics.
CONCLUSION: Most PEx identified in clinic are treated with new oral and/or inhaled antibiotics. Markers of disease severity are associated with antibiotic treatment choice. Many patients had no follow-up evaluation within 90 days of treatment.

PMID: 31257102 [PubMed - as supplied by publisher]

Fertility of women with cystic fibrosis: a French survey.

Reprod Biomed Online. 2019 May 07;:

Authors: Tournier A, Murris M, Prevotat A, Fanton A, Bettiol C, Parinaud J

Abstract
RESEARCH QUESTION: Although the impact of cystic fibrosis on male fertility is well known, very few studies have investigated its effect on female fertility. This study aimed to evaluate the fertility status of women with cystic fibrosis.
DESIGN: A questionnaire was sent to 220 women with cystic fibrosis. The questions concerned their desire to become a parent, achievement or not of a pregnancy, the time to become pregnant, the means of achieving pregnancy (spontaneously or with medical assistance) and the outcome of the pregnancy. Ninety-eight patients responded to the questionnaire.
RESULTS: Of the 46 women who sought pregnancy, 25 (54%) had at least one live birth without treatment, while 11 (24%) required infertility treatment to obtain a live birth and 10 (22%) had no delivery. The mean time-to-pregnancy was 12 months (1-180). The reasons for preferring not to become pregnant were mainly fear of the interaction between cystic fibrosis and pregnancy and of the transmission of cystic fibrosis to children.
CONCLUSIONS: Fertility seems to be slightly impaired in women with cystic fibrosis, because 37% of them failed to become pregnant without medical assistance. Because the outcome of pregnancies appears normal, patients should be informed about the possibility of becoming mothers and be made aware of the risk of unwanted pregnancies.

PMID: 31256948 [PubMed - as supplied by publisher]

Zebrafish aversive taste co-receptor is expressed in both chemo- and mechanosensory cells and plays a role in lateral line development.

Sci Rep. 2017 10 18;7(1):13475

Authors: Mojib N, Xu J, Bartolek Z, Imhoff B, McCarty NA, Shin CH, Kubanek J

Abstract
Fishes rely on both chemical and tactile senses to orient themselves to avoid predators, and to detect and taste food. This is likely achieved by highly coordinated reception of signals by mechano- and chemosensory receptors in fish. A small co-receptor from zebrafish, receptor activity modifying protein (RAMP)-like triterpene glycoside receptor (RL-TGR), was previously found to be involved in recognition of triterpene glycosides, a family of naturally occurring compounds that act as chemical defenses in various prey species. However, its localization, function, and how it impacts sensory organ development in vivo is not known. Here we show that RL-TGR is expressed in zebrafish in both i) apical microvilli of the chemosensory cells of taste buds including the epithelium of lips and olfactory epithelium, and ii) mechanosensory cells of neuromasts belonging to the lateral line system. Loss-of-function analyses of RL-TGR resulted in significantly decreased number of neuromasts in the posterior lateral line system and decreased body length, suggesting that RL-TGR is involved in deposition and migration of the neuromasts. Collectively, these results provide the first in vivo genetic evidence of sensory cell-specific expression of this unusual co-receptor and reveal its additional role in the lateral line development in zebrafish.

PMID: 29044184 [PubMed - indexed for MEDLINE]

Increased intracellular Cl- concentration mediates Trichomonas vaginalis-induced inflammation in the human vaginal epithelium.

Int J Parasitol. 2019 Jun 26;:

Authors: Xu JB, Zhang YL, Huang J, Lu SJ, Sun Q, Chen PX, Jiang P, Qiu ZE, Jiang FN, Zhu YX, Lai DH, Zhong WD, Lun ZR, Zhou WL

Abstract
Trichomonas vaginalis is a primary urogenital parasite that causes trichomoniasis, a common sexually transmitted disease. As the first line of host defense, vaginal epithelial cells play critical roles in orchestrating vaginal innate immunity and modulate intracellular Cl- homeostasis via the cystic fibrosis transmembrane conductance regulator (CFTR), an anion channel that plays positive roles in regulating nuclear factor-κB (NF-κB) signaling. However, the association between T. vaginalis infection and intracellular Cl- disequilibrium remains elusive. This study showed that after T. vaginalis infection, CFTR was markedly down-regulated by cysteine proteases in vaginal epithelial cells. The intracellular Cl- concentration ([Cl-]i) was consequently elevated, leading to NF-κB signaling activation via serum- and glucocorticoid-inducible kinase-1. Moreover, heightened [Cl-]i and activated NF-κB signaling could be sustained in a positive feedback regulatory manner resulting from decreased intracellular cAMP through NF-κB-mediated up-regulation of phosphodiesterase 4.,The results conclusively revealed that the intracellular Cl- of the human vaginal epithelium could be dynamically modulated by T. vaginalis, which contributed to mediation of epithelial inflammation in the human vagina.

PMID: 31254529 [PubMed - as supplied by publisher]

Longitudinal associations between gratitude and depression 1 year later among adult cystic fibrosis patients.

J Behav Med. 2019 Jun 28;:

Authors: Sherman AC, Simonton-Atchley S, O'Brien CE, Campbell D, Reddy RM, Guinee B, Wagner LD, Anderson PJ

Abstract
Individuals with cystic fibrosis (CF) are confronted by a range of difficult physical and psychosocial sequelae. Gratitude has drawn growing attention as a psychosocial resource, but it has yet to be examined among adults with CF. The current investigation evaluated longitudinal associations between trait gratitude and subsequent outcomes from depression screening 12 months later, adjusting for disease severity (FEV1% predicted) and other significant clinical or demographic covariates. Participants were 69 adult CF patients recruited from a regional adult treatment center. They completed a validated measure of gratitude (Gratitude Questionnaire-6) at baseline and a screening measure of depression (Hospital Anxiety and Depression Scale) at 12-month follow-up. In a logistic regression analysis controlling for disease severity, higher levels of baseline gratitude were associated with reduced likelihood of depression caseness at 12 months (OR .83, 95% CI .73-.91, p = .001). Gratitude remained predictive after adjusting for other psychosocial resource variables (i.e., perceived social support and positive reframing coping). Findings offer an initial indication of the potential salutary role of dispositional gratitude in an understudied clinical population.

PMID: 31254218 [PubMed - as supplied by publisher]

Antimicrobial stewardship impact on Pseudomonas aeruginosa susceptibility to meropenem at a tertiary pediatric institution.

Am J Infect Control. 2019 Jun 25;:

Authors: Stultz JS, Arnold SR, Shelton CM, Bagga B, Lee KR

Abstract
An antimicrobial stewardship program was implemented throughout 2012 at a tertiary pediatric institution with guideline development preceding prospective audit and feedback starting in 2013. Meropenem use decreased over 62% during the next 5 years. Non-cystic fibrosis Pseudomonas aeruginosa isolate susceptibility to meropenem increased from 89% in 2011 to 98% in 2017 (P < .001) and correlated with meropenem use the preceding year (Rs: -0.78, P = .008).

PMID: 31253550 [PubMed - as supplied by publisher]

Variation in lung function and nutritional decline in cystic fibrosis by genotype: An analysis of the Canadian cystic fibrosis registry.

J Cyst Fibros. 2019 Jun 25;:

Authors: Leung GJ, Cho TJ, Kovesi T, Hamid JS, Radhakrishnan D

Abstract
BACKGROUND: This study aimed to improve our understanding of the natural history of cystic fibrosis (CF) by comparing lung function and body mass index z-score (zBMI) between patients with different genotypes and identify a genotype with outcomes most comparable to homozygous ΔF508 patients.
METHODS: Data was obtained from the Canadian CF Registry between January 1st 2007-January 1st 2016. Patients were categorized into one of five groups based on their genotype. A mixed-effects model was conducted with adjustments for age, sex, age of diagnosis, and baseline clinical measures.
RESULTS: Among 2612 patients, those with non-mild forms of CF, and particularly adult patients with the same functional allele classification were found to have a lung function trajectory comparable to individuals with the homozygous ∆F508 genotype (annual change in percent predicted forced expiratory volume in 1 s of -0.83, 95% CI: -0.93, -0.73). The rates of zBMI change over the study period were not significantly different between the genotype groups.
CONCLUSION: This population-based study of Canadian CF patients provides adjusted rates of lung function decline and zBMI over ten years. The finding that there are different genotypes with comparable rates of lung function decline to patients of the homozygous ∆F508 group supports the use of multiple comparison groups to assess the long-term efficacy of emerging CF therapies.

PMID: 31253541 [PubMed - as supplied by publisher]

A phase 3 study of tezacaftor in combination with ivacaftor in children aged 6 through 11 years with cystic fibrosis.

J Cyst Fibros. 2019 Jun 25;:

Authors: Walker S, Flume P, McNamara J, Solomon M, Chilvers M, Chmiel J, Harris RS, Haseltine E, Stiles D, Li C, Ahluwalia N, Zhou H, Owen CA, Sawicki G, VX15-661-113 Investigator Group

Abstract
BACKGROUND: Tezacaftor/ivacaftor is a new treatment option in many regions for patients aged ≥12 years who are homozygous (F/F) or heterozygous for the F508del-CFTR mutation and a residual function (F/RF) mutation. This Phase 3, 2-part, open-label study evaluated the pharmacokinetics (PK), safety, tolerability, and efficacy of tezacaftor/ivacaftor in children aged 6 through 11 years with these mutations.
METHODS: Part A informed weight-based tezacaftor/ivacaftor dosages for part B. The primary objective of part B was to evaluate the safety and tolerability of tezacaftor/ivacaftor through 24 weeks; the secondary objective was to evaluate efficacy based on changes from baseline in percentage predicted forced expiratory volume in 1 s (ppFEV1), growth parameters, sweat chloride, and the Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score.
RESULTS: After PK analysis in part A, 70 children received ≥1 dose of tezacaftor/ivacaftor in part B; 67 children completed treatment. Exposures in children aged 6 through 11 years were within the target range for those observed in patients aged ≥12 years. The safety profile of tezacaftor/ivacaftor was generally similar to prior studies in patients aged ≥12 years. One child discontinued treatment for a serious adverse event of constipation. Tezacaftor/ivacaftor treatment improved sweat chloride levels and CFQ-R respiratory domain scores, mean ppFEV1 remained stable in the normal range, and growth parameters remained stable over 24 weeks.
CONCLUSIONS: Tezacaftor/ivacaftor was generally safe and well tolerated, and improved CFTR function in children aged 6 through 11 years with CF with F/F and F/RF genotypes, supporting tezacaftor/ivacaftor use in this age group. NCT02953314.

PMID: 31253540 [PubMed - as supplied by publisher]

Diversity of Achromobacter species recovered from patients with cystic fibrosis, in Argentina.

Rev Argent Microbiol. 2019 Jun 25;:

Authors: Papalia M, Steffanowski C, Traglia G, Almuzara M, Martina P, Galanternik L, Vay C, Gutkind G, Ramírez MS, Radice M

Abstract
Different phenotype-based techniques and molecular tools were used to describe the distribution of different Achromobacter species in patients with cystic fibrosis (CF) in Argentina, and to evaluate their antibiotic resistance profile. Phenotypic identification was performed by conventional biochemical tests, commercial galleries and MALDI-TOF MS. Genetic approaches included the detection of A. xylosoxidans specific marker blaoxa-114, the amplification and sequencing of the 16S rRNA gene, nrdA and blaOXA complete sequence, and MLST analysis. Phenotypic approaches, even MALDI-TOF, rendered inconclusive or misleading results. On the contrary, concordant results were achieved with the nrdA sequencing or sequence type (ST) analysis, and the complete blaOXA sequencing, allowing a reliable discrimination of different Achromobacter species. A. xylosoxidans accounted for 63% of Achromobacter infections and A. ruhlandii accounted for 17%. The remaining species corresponded to A. insuavis, A. dolens, A. marplatensis and A. pulmonis. Antimicrobial susceptibilities were determined by the agar dilution method according to CLSI guidelines. Piperacillin, piperacillin/tazobactam and carbapenems were the most active antibiotics. However, the emergence of carbapenem-resistant isolates was detected. In conclusion, prompt and accurate identification tools were necessary to determine that different Achromobacter species may colonize/infect the airways of patients with CF. Moreover, antimicrobial therapy should be administered based on the susceptibility profile of individual Achromobacter sp. isolates.

PMID: 31253503 [PubMed - as supplied by publisher]

Transcriptome analysis of the distal small intestine of Cftr null mice.

Genomics. 2019 Jun 25;:

Authors: Ikpa PT, Meijsen KF, Nieuwenhuijze NDA, Dulla K, de Jonge HR, Bijvelds MJC

Abstract
Cystic fibrosis (CF) is caused by mutations in the gene encoding the CFTR anion channel. Loss of CFTR function in pancreatic, biliary and intestinal epithelia, severely affects gastrointestinal function. Transcriptome analysis indicated the activation of an innate and adaptive immune response in the distal small intestine of Cftr null mice. Inflammation was associated with differential regulation of numerous genes involved in the transport and metabolism of nutrients and, particularly, lipids, that are targeted by ligand-dependent nuclear receptors and/or HNF4α. Among the most strongly down-regulated genes are the FXR targets Fgf15 and Nr0b2, the PPARα target Pdk4, and the PXR target Ces2a, whereas expression of the CF modifier gene Slc6a14 was strongly increased. Most changes in gene expression were reversed by bacterial containment. Our data suggest that the gut microbiota has a pervasive effect on gene expression in CF mice, affecting enterocyte maturation, lipid metabolism, and nutrient absorption in CF.

PMID: 31251978 [PubMed - as supplied by publisher]

Evaluation of eluforsen, a novel RNA oligonucleotide for restoration of CFTR function in in vitro and murine models of p.Phe508del cystic fibrosis.

PLoS One. 2019;14(6):e0219182

Authors: Beumer W, Swildens J, Leal T, Noel S, Anthonijsz H, van der Horst G, Kuiperij-Boersma H, Potman M, van Putten C, Biasutto P, Platenburg G, de Jonge H, Henig N, Ritsema T

Abstract
Cystic fibrosis (CF) is caused by mutations in the gene encoding the epithelial chloride channel CF transmembrane conductance regulator (CFTR) protein. The most common mutation is a deletion of three nucleotides leading to the loss of phenylalanine at position 508 (p.Phe508del) in the protein. This study evaluates eluforsen, a novel, single-stranded, 33-nucleotide antisense oligonucleotide designed to restore CFTR function, in in vitro and in vivo models of p.Phe508del CF. The aims of the study were to demonstrate cellular uptake of eluforsen, and its efficacy in functional restoration of p.Phe508del-CFTR both in vitro and in vivo. In vitro, the effect of eluforsen was investigated in human CF pancreatic adenocarcinoma cells and human bronchial epithelial cells. Two mouse models were used to evaluate eluforsen in vivo. In vitro, eluforsen improved chloride efflux in CF pancreatic adenocarcinoma cell cultures and increased short-circuit current in primary human bronchial epithelial cells, both indicating restoration of CFTR function. In vivo, eluforsen was taken up by airway epithelium following oro-tracheal administration in mice, resulting in systemic exposure of eluforsen. In female F508del-CFTR mice, eluforsen significantly increased CFTR-mediated saliva secretion (used as a measure of CFTR function, equivalent to the sweat test in humans). Similarly, intranasal administration of eluforsen significantly improved nasal potential difference (NPD), and therefore CFTR conductance, in two CF mouse models. These findings indicate that eluforsen improved CFTR function in cell and animal models of p.Phe508del-CFTR-mediated CF and supported further development of eluforsen in human clinical trials, where eluforsen has also been shown to improve CFTR activity as measured by NPD.

PMID: 31251792 [PubMed - in process]

Computer and mobile technology interventions to promote medication adherence and disease management in people with thalassemia.

Cochrane Database Syst Rev. 2019 Jun 28;6:CD012900

Authors: Badawy SM, Morrone K, Thompson A, Palermo TM

Abstract
BACKGROUND: Thalassemia syndromes are inherited hemoglobin disorders that result when the synthesis of normal hemoglobin is lacking or significantly reduced. For people with thalassemia, long-term red blood cell transfusion remains the mainstay of therapy, which may lead to iron overload causing severe complications and damage in different body organs. Long-term iron chelation therapy is essential for people with thalassemia to minimize the ongoing iron-loading process. In addition, suboptimal adherence can increase adverse events associated with iron overload and result in increased morbidity, mortality, healthcare utilization and cost of care.
OBJECTIVES: To identify and assess the effects of computer and mobile technology interventions designed to facilitate medication adherence and disease management in individuals with thalassemia, including:- evaluating the effects of using computer and mobile technology interventions for medication adherence and disease management on health and behavioral outcomes;- identifying and assessing the effects of computer and mobile technology interventions specific to different age groups (children, adolescents and adults) and type of modality (e.g. cell phone, the Internet).
SEARCH METHODS: We searched CENTRAL (the Cochrane Library), MEDLINE, Embase, CINAHL, PsycINFO, ProQuest Dissertations & Theses Global, Psychology and Behavioral Sciences Collection, Web of Science Science & Social Sciences Conference Proceedings Indexes, IEEE Xplore and ongoing trial databases (22 February 2018). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register (20 June 2019). We also searched for unpublished work in the abstract book of nine major conferences in the related field.
SELECTION CRITERIA: Randomized controlled trials (RCT) and quasi-RCTs comparing single- or multi-component interventions versus no intervention, placebo or standard care, with adherence to iron chelation as the primary outcome were eligible for inclusion. Non-randomized studies of interventions, controlled before-after studies, and interrupted-time-series studies were also eligible for inclusion.
DATA COLLECTION AND ANALYSIS: Three authors independently assessed study eligibility. If we had included any studies, we would have independently assessed risk of bias and extracted data; we planned to assess the quality of the evidence using GRADE.
MAIN RESULTS: We did not identify any eligible studies for inclusion in the review.
AUTHORS' CONCLUSIONS: Due to lack of evidence, we cannot comment on the efficacy or effectiveness of computer and mobile technology intervention strategies to promote disease management and adherence to iron chelation therapy in people with thalassemia.We concluded that RCTs are needed to examine a variety of computer and mobile technology intervention strategies that may be useful for promoting disease management and increasing adherence to iron chelation therapy in individuals with thalassemia.

PMID: 31250923 [PubMed - as supplied by publisher]

Using qualitative methods to inform the design of a decision aid for people with advanced cystic fibrosis: The InformedChoices CF patient decision aid.

Patient Educ Couns. 2019 Jun 22;:

Authors: Basile M, Andrews J, Wang J, Hadjiliadis D, Henthorne K, Fields S, Kozikowski A, Huamantla J, Hajizadeh N

Abstract
OBJECTIVE: To assess information needs of adults with Cystic Fibrosis and their families toward designing a patient decision aid about invasive mechanical ventilation (IMV) and lung transplant.
METHODS: Focus groups and in-depth interviews explored participants' knowledge, prior clinical conversations, and decisions about IMV and lung transplant. Interviews and focus groups were recorded and transcribed for analysis.
RESULTS: N = 24 participants were recruited. Themes identified were: prior communication with clinicians, decision-making process, and living with CF. Participants having prior conversations with CF clinicians regarding: lung transplant (N = 17/74%), and IMV (N = 3/13%). Most 15(65%) felt it was important to hear patients' real-life experience, others (3/13%) relied on their CF doctors for information. Most people (16/70%) believed hearing prognosis was helpful, but 5(22%) found this information frightening. High degrees of social isolation and a desire for more interaction with other CF adults were found.
CONCLUSIONS: Qualitative methods helped identify areas important for decision making about IMV and LT for CF adults. Future directions include usability and feasibility testing of the decision aid.
PRACTICE IMPLICATIONS: Because IMV is rarely discussed with CF adults, clinicians might approach this topic, as with transplant, as lung function begins to decline. CF-care teams should also foster CF patient-level information exchange.

PMID: 31248766 [PubMed - as supplied by publisher]

Long-Term Intrahost Evolution of Methicillin Resistant Staphylococcus aureus Among Cystic Fibrosis Patients With Respiratory Carriage.

Front Genet. 2019;10:546

Authors: Azarian T, Ridgway JP, Yin Z, David MZ

Abstract
Staphylococcus aureus is the most commonly identified airway colonizer of cystic fibrosis (CF) patients, and infections with methicillin-resistant S. aureus (MRSA) are associated with poor outcomes. Yet, little is known about the intrahost evolution of S. aureus among CF patients. We investigated convergent evolution and adaptation of MRSA among four CF patients with long-term respiratory carriage. For each patient, we performed whole-genome sequencing on an average of 21 isolates (range: 19-23) carried for a mean of 1,403 days (range: 903-1,679), including 25 pairs of isolates collected on the same day. We assessed intrahost diversity, population structure, evolutionary history, evidence of switched intergenic regions (IGRs), and signatures of adaptation in the context of patient age, antibiotic treatment, and co-colonizing microbes. Phylogenetic analysis delineated distinct multilocus sequence type ST5 (n = 3) and ST72 (n = 1) clonal populations in addition to sporadic, non-clonal isolates, and uncovered a putative transmission event. Variation in antibiotic resistance was observed within clonal populations, even among isolates collected on the same day. Rates of molecular evolution ranged from 2.21 to 8.64 nucleotide polymorphisms per year, and lineage ages were consistent with acquisition of colonization in early childhood followed by subsequent persistence of multiple sub-populations. Selection analysis of 1,622 core genes present in all four clonal populations (n = 79) found 11 genes variable in three subjects - most notably, ATP-dependent protease clpX, 2-oxoglutarate dehydrogenase odhA, fmtC, and transcription-repair coupling factor mfd. Only one gene, staphylococcal protein A (spa), was found to have evidence of gene-wide diversifying selection. We identified three instances of intrahost IGR switching events, two of which flanked genes related to quorum sensing. The complex microbial ecology of the CF airway poses challenges for management. We illustrate appreciable intrahost diversity as well as persistence of a dominant lineage. We also show that intrahost adaptation is a continual process, despite purifying selective pressure, and provide targets that should be investigated further for their function in CF adaptation.

PMID: 31244886 [PubMed]

Identification of 99% of CFTR gene mutations in Bulgarian-, Bulgarian Turk-, and Roma cystic fibrosis patients.

Mol Genet Genomic Med. 2019 Jun 27;:e696

Authors: Petrova G, Yaneva N, Hrbková J, Libik M, Savov A, Macek M

Abstract
BACKGROUND: The spectrum and frequencies of CFTR mutations causing Cystic fibrosis (CF) varies among different populations in Europe, and beyond.
METHODS: We identified 98.9% of all CFTR mutations in a representative cohort of 140 CF patients comprising 107 Bulgarian- (BG), 17 BG Turk-, and 16 BG Roma cases. The compiled clinical and genotype dataset includes 110 previously analyzed patients with 30 cases currently analyzed for rare CFTR variants by massively parallel sequencing of the entire CFTR coding region and adjacent introns combined with the analysis of intra-CFTR rearrangements.
RESULTS: Altogether 53 different mutations, of which 15 newly identified in the BG CF population, were observed. Comparison of clinical and laboratory data between individual BG ethnic groups proved that BG Roma have a more severe nutritional status and are younger than other CF patients, as well as that the spectrum mutations differs between them.
CONCLUSION: This collaborative study improves genetic counselling in BG, facilitates introduction of multitier CF neonatal screening and fosters public health measures for improvement of care in the Roma CF population.

PMID: 31245908 [PubMed - as supplied by publisher]

Autosomal recessive diseases among the Israeli Arabs.

Hum Genet. 2019 Jun 26;:

Authors: Zlotogora J

Abstract
The Israeli population mainly includes Jews, Muslim and Christian Arabs, and Druze. Data on genetic diseases present in the population have been systematically collected and are available online in the Israeli national genetic database. Among the Israeli Arabs in December 31 2018, the database included molecular data on six diseases relatively frequent in the whole population: thalassemia, familial Mediterranean fever (FMF), cystic fibrosis, deafness, phenylketonuria or congenital adrenal hyperplasia as well as data on 632 autosomal recessive diseases among Muslim Israeli Arabs, 52 among the Christian Arabs and 79 among Druze. A single variant was characterized in 590 out of the 771 genes causing disorders in which the molecular basis was known. Many of the variants reported among Arabs in Israel are novels, most being found in one community only. Some variants are ancient and for instance, consistent with the migration history, several variants are found in the Bedouins from the Negev as well as from the Arab peninsula. In the 181 other disorders more than one variant was characterized either in the same gene or in more than one gene. While it is probable that most of these cases represent random events in some cases the reason may be a selective advantage to the heterozygotes.

PMID: 31243543 [PubMed - as supplied by publisher]

Successful preservation and transplant of warm ischaemic lungs from controlled donors after circulatory death by prolonged in situ ventilation during normothermic regional perfusion of abdominal organs.

Interact Cardiovasc Thorac Surg. 2019 Jun 26;:

Authors: Palleschi A, Tosi D, Rosso L, Zanella A, De Carlis R, Zanierato M, Benazzi E, Tarsia P, Colledan M, Nosotti M

Abstract
OBJECTIVES: Donation after circulatory death (DCD) potentially provides transplantable lungs suitable for a transplant, but in Italy, the need for 20 min of a no-touch period after cardiac arrest for legal declaration of death poses real challenges to organ preservation.
METHODS: This is a single-institution, retrospective study using data collected prospectively between October and December 2017. After the approval of the multidisciplinary DCD study group of Regione Lombardia, Maastricht category III DCD donors became eligible for combined procurement of lungs and abdominal organs. Our group subsequently established a dedicated technical protocol. Our protocol consists of a non-rapid normothermic open-lung procurement process that takes place during abdominal normothermic regional perfusion, namely without pleural topical cooling before the start of pneumoplegia. After the lung is procured according to the technique described in the article, lung function is evaluated by ex vivo lung perfusion, which is run with the low-flow, open atrium, low haematocrit technique.
RESULTS: During the study, we managed 5 controlled DCDs. In 3 cases, the lungs were successfully transplanted. All 3 patients are alive after 1 year, with good respiratory function.
CONCLUSIONS: Our approach resulted in adequate lung preservation and successful transplants without detrimental effects on abdominal organ procurement, confirming the possibility of overcoming the obstacle of a long no-touch period in a DCD setting.

PMID: 31243436 [PubMed - as supplied by publisher]

Sensors for detecting pulmonary diseases from exhaled breath.

Eur Respir Rev. 2019 Jun 30;28(152):

Authors: Hashoul D, Haick H

Abstract
This review presents and discusses a new frontier for fast, risk-free and potentially inexpensive diagnostics of respiratory diseases by detecting volatile organic compounds (VOCs) present in exhaled breath. One part of the review is a didactic presentation of the overlaying concept and the chemistry of exhaled breath. The other part discusses diverse sensors that have been developed and used for the detection of respiratory diseases (e.g. chronic obstructive pulmonary disease, asthma, lung cancer, pulmonary arterial hypertension, tuberculosis, cystic fibrosis, obstructive sleep apnoea syndrome and pneumoconiosis) by analysis of VOCs in exhaled breath. The strengths and pitfalls are discussed and criticised, particularly in the perspective in disseminating information regarding these advances. Ideas regarding the improvement of sensors, sensor arrays, sensing devices and the further planning of workflow are also discussed.

PMID: 31243097 [PubMed - in process]

Using a stated preference discrete choice experiment to assess societal value from the perspective of patients with rare diseases in Italy.

Orphanet J Rare Dis. 2019 Jun 26;14(1):154

Authors: López-Bastida J, Ramos-Goñi JM, Aranda-Reneo I, Taruscio D, Magrelli A, Kanavos P

Abstract
BACKGROUND: Decision makers have huge problems when attempting to attribute social value to the improvements achieved by new drugs, especially when considering the use of orphan drugs for rare diseases. We present the results of a pilot study aimed to investigate patient preferences regarding public funding for drugs used to treat rare diseases.
METHODS: An online questionnaire was used as a discrete choice experiment (DCE) survey to explore the preferences of patients with cystic fibrosis and haemophilia in Italy. The questionnaire focused on relevant issues that were defined in a review of the literature. A conditional logistic model showed preferences for specific attributes.
RESULTS: A total of 54 questionnaires (20% response rate) were completed. The issues that received the greatest attention were improvement in health, treatment cost and value for money. However, disease severity and the availability of other treatments were important social values that could not be ignored.
CONCLUSIONS: The findings presented here provide evidence as to what patients with cystic fibrosis or haemophilia think are the most important considerations on which to base decisions in health technology scenarios, and regarding the priorities for funding.

PMID: 31242905 [PubMed - in process]

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