Elementary, My Dear Watson! The Accumulating Evidence for the Lung Clearance Index in Monitoring Early Cystic Fibrosis Lung Disease.

Am J Respir Crit Care Med. 2017 May 01;195(9):1131-1132

Authors: Pittman J, Rosenfeld M

PMID: 28459345 [PubMed - in process]

AJRCCM: 100-Year Anniversary. Progress along the Pathway of Discovery Leading to Treatment and Cure of Cystic Fibrosis.

Am J Respir Crit Care Med. 2017 May 01;195(9):1092-1099

Authors: Ramsey BW, Welsh MJ

PMID: 28459323 [PubMed - in process]

Innate immunity and chronic rhinosinusitis: What we have learned from animal models.

Laryngoscope Investig Otolaryngol. 2016 Jun;1(3):49-56

Authors: London NR, Lane AP

Abstract
OBJECTIVE: Chronic rhinosinusitis (CRS) is a heterogeneous and multifactorial disease characterized by dysregulated inflammation. Abnormalities in innate immune function including sinonasal epithelial cell barrier function, mucociliary clearance, response to pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs), and the contribution of innate immune cells will be highlighted in this review.
DATA SOURCES: PubMed literature review.
REVIEW METHODS: A review of the literature was conducted to determine what we have learned from animal models in relation to innate immunity and chronic rhinosinusitis.
RESULTS: Dysregulation of innate immune mechanisms including sinonasal barrier function, mucociliary clearance, PAMPs, and innate immune cells such as eosinophils, mast cells, and innate lymphoid cells may contribute to CRS pathogenesis. Sinonasal inflammation has been studied using mouse, rat, rabbit, pig, and sheep explant or in vivo models. Study using these models has allowed for analysis of experimental therapeutics and furthered our understanding of the aforementioned aspects of the innate immune mechanism as it relates to sinonasal inflammation. These include augmenting mucociliary clearance through activation of the cystic fibrosis transmembrane conductance regulator (CFTR) and study of drug toxicity on ciliary beat frequency. Knockout models of Toll-like receptors (TLR) have demonstrated the critical role these PRRs play in allergic inflammation as loss of TLR2 and TLR4 leads to decreased lower airway inflammation. Mast cell deficient mice are less susceptible to ovalbumin-induced sinonasal inflammation.
CONCLUSION: Animal models have shed light as to the potential contribution of dysregulated innate immunity in chronic sinonasal inflammation.

PMID: 28459101 [PubMed - in process]

In vitro Multi-Species Biofilms of Methicillin-Resistant Staphylococcus aureus and Pseudomonas aeruginosa and Their Host Interaction during In vivo Colonization of an Otitis Media Rat Model.

Front Cell Infect Microbiol. 2017;7:125

Authors: Yadav MK, Chae SW, Go YY, Im GJ, Song JJ

Abstract
Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) are known to cause biofilm-related infections. MRSA and PA have been frequently isolated from chronically infected wounds, cystic fibrosis, chronic suppurative otitis media (CSOM), and from indwelling medical devices, and these bacteria co-exist; however, their interaction with each-other or with the host is not well known. In this study, we investigated MRSA and PA multi-species biofilm communities in vitro and their interaction with the host during in vivo colonization using an OM rat-model. In-vitro biofilm formation and in-vivo colonization were studied using CV-microtiter plate assay and OM rat-model respectively. The biofilms were viewed under scanning electron microscope and bacteria were enumerated using cfu counts. The differential gene expressions of rat mucosa colonized with single or multi-species of MRSA or PA were studied using RNA-sequencing of total transcriptome. In multi-species in-vitro biofilms PA partially inhibited SA growth. However, no significant inhibition of MRSA was detected during in-vivo colonization of multi-species in rat bullae. A total of 1,797 genes were significantly (p < 0.05) differentially expressed in MRSA or PA or MRSA + PA colonized rat middle ear mucosa with respect to the control. The poly-microbial colonization of MRSA and PA induced the differential expression of a significant number of genes that are involved in immune response, inflammation, signaling, development, and defense; these were not expressed with single species colonization by either MRSA or PA. Genes involved in defense, immune response, inflammatory response, and developmental process were exclusively up-regulated, and genes that are involved in nervous system signaling, development and transmission, regulation of cell growth and development, anatomical and system development, and cell differentiation were down-regulated after multi-species inoculation. These results indicate that poly-microbial colonization induces a host response that is different from that induced by single species infection.

PMID: 28459043 [PubMed - in process]

Inflammatory Responses Regulating Alveolar Ion Transport during Pulmonary Infections.

Front Immunol. 2017;8:446

Authors: Peteranderl C, Sznajder JI, Herold S, Lecuona E

Abstract
The respiratory epithelium is lined by a tightly balanced fluid layer that allows normal O2 and CO2 exchange and maintains surface tension and host defense. To maintain alveolar fluid homeostasis, both the integrity of the alveolar-capillary barrier and the expression of epithelial ion channels and pumps are necessary to establish a vectorial ion gradient. However, during pulmonary infection, auto- and/or paracrine-acting mediators induce pathophysiological changes of the alveolar-capillary barrier, altered expression of epithelial Na,K-ATPase and of epithelial ion channels including epithelial sodium channel and cystic fibrosis membrane conductance regulator, leading to the accumulation of edema and impaired alveolar fluid clearance. These mediators include classical pro-inflammatory cytokines such as TGF-β, TNF-α, interferons, or IL-1β that are released upon bacterial challenge with Streptococcus pneumoniae, Klebsiella pneumoniae, or Mycoplasma pneumoniae as well as in viral infection with influenza A virus, pathogenic coronaviruses, or respiratory syncytial virus. Moreover, the pro-apoptotic mediator TNF-related apoptosis-inducing ligand, extracellular nucleotides, or reactive oxygen species impair epithelial ion channel expression and function. Interestingly, during bacterial infection, alterations of ion transport function may serve as an additional feedback loop on the respiratory inflammatory profile, further aggravating disease progression. These changes lead to edema formation and impair edema clearance which results in suboptimal gas exchange causing hypoxemia and hypercapnia. Recent preclinical studies suggest that modulation of the alveolar-capillary fluid homeostasis could represent novel therapeutic approaches to improve outcomes in infection-induced lung injury.

PMID: 28458673 [PubMed - in process]

Standardized Treatment of Pulmonary exacerbations (STOP) study: Physician treatment practices and outcomes for individuals with cystic fibrosis with pulmonary exacerbations.

J Cyst Fibros. 2017 Apr 27;:

Authors: West NE, Beckett VV, Jain R, Sanders DB, Nick JA, Heltshe SL, Dasenbrook EC, VanDevanter DR, Solomon GM, Goss CH, Flume PA, STOP investigators

Abstract
BACKGROUND: Pulmonary exacerbations (PEx) are associated with increased morbidity and mortality in individuals with CF. PEx management practices vary widely, and optimization through interventional trials could potentially improve outcomes. The object of this analysis was to evaluate current physician treatment practices and patient outcomes for PEx.
METHODS: The Standardized Treatment of Pulmonary exacerbations (STOP) observational study enrolled 220 participants ≥12years old admitted to the hospital for PEx at 11 U.S. CF centers. Spirometry and daily symptom scores were collected during the study. Physicians were surveyed on treatment goals and their management practices were observed. Treatment outcomes were compared to stated goals.
RESULTS: The mean (SD) duration of IV antibiotic treatment was 15.9 (6.0) days. Those individuals with more severe lung disease (<50% FEV1) were treated nearly two days longer than those with >50% FEV1. Physician-reported FEV1 improvement goals were 10% (95% CI: 5%, 14%) lower for patients with 6-month baseline FEV1 ≤50% predicted compared with those with 6-month baseline FEV1 >50% predicted. There were clinically and statistically significant improvements in symptoms from the start of IV antibiotic treatment to the end of IV antibiotic treatment and 28days after the start of treatment. The mean absolute increase in FEV1 from admission was 9% predicted at end of IV antibiotic treatment, and 7% predicted at day 28. Only 39% fully recovered lost lung function, and only 65% recovered at least 90% of lost lung function. Treatment was deemed successful by 84% of clinicians, although 6-month baseline FEV1 was only recovered in 39% of PEx.
CONCLUSIONS: In this prospective observational study of PEx, treatment regimens and durations showed substantial variation. A significant proportion of patients did not reach physician's treatment goals, yet treatment was deemed successful.

PMID: 28457954 [PubMed - as supplied by publisher]

In vitro activity of a novel compound, mul-1867, against clinically significant fungi candida spp. and aspergillus spp.

Int J Antimicrob Agents. 2017 Apr 27;:

Authors: Tetz G, Cynamon M, Hendricks G, Vikina D, Tetz V

Abstract
There is an urgent need for new antifungal compounds to treat various types of fungal infections, including pulmonary infections. This study was designed to investigate the potency of a novel compound (Mul-1867) against Candida spp. and Aspergillus spp. isolated from patients with fungal pneumonia, cystic fibrosis and chronic obstructive pulmonary disease. Mul-1867 was highly effective against susceptible control strains as well as resistant clinical isolates, with minimum fungicidal concentrations (MFCs) varying from 0.06 µg/mL to 0.5 µg/mL. It was also highly effective against pre-formed 48-h-old biofilms formed by yeasts and moulds. The half-minimal biofilm eradication concentration (MBEC50) was equal to the MFC. The minimum biofilm eradication concentration to eliminate 90% of biofilms (MBEC90) varied from 1× to 4× MFC. Scanning electron microscopy revealed morphological changes accompanied by the release of intracellular material from the fungal cells following exposure to Mul-1867. Furthermore, an increased concentration of nucleic acids was found in the medium after 5 min and 20 min of Mul-1867 treatment, indicating leakage of cytoplasmic contents. Overall, these data indicate that Mul-1867 may be a promising inhaled antifungal agent for the treatment and prevention of fungal respiratory infections.

PMID: 28457835 [PubMed - as supplied by publisher]

Lung Transplantation From Donors After Previous Cardiac Surgery: Ideal Graft in Marginal Donor?

Transplant Proc. 2017 May;49(4):686-691

Authors: Palleschi A, Mendogni P, Tosi D, Montoli M, Carrinola R, Mariolo AV, Briganti F, Nosotti M

Abstract
Lung transplantation is a limited by donor pool shortage. Despite the efforts to extend the graft acceptability with recurrent donor criteria reformulations, previous cardiothoracic surgery is still considered a contraindication. A donor who underwent cardiac surgery could potentially provide an ideal lung but high intraoperative risks and intrinsic technical challenges are expected during the graft harvesting. The purpose of this study is to present our dedicated protocol and four clinical cases of successful lung procurements from donors who had a previous major cardiac surgery. One donor had ascending aortic root (AAR) substitution, another had mitral valve substitution, and two had coronary artery bypass surgery. The others' eligibility criteria for organ allocation, such as ABO compatibility, PaO2/FiO2 ratio, absence of aspiration, or sepsis were respected. In one of the cases with previous coronary bypass grafting, the donor had a veno-arterial extracorporeal membrane oxygenation support. Consequently, the grafts required an ex vivo lung perfusion evaluation. We report the technical details of procurement and postoperative courses of recipients. All procurements were uneventful, without lung damage or waste of abdominal organs related to catastrophic intraoperative events. All recipients had a successful clinical outcome. We believe that successful transplantation is achievable even in a complicated setting, such as cases involving donors with previous cardiac surgery frequently are. Facing lung donor shortage, we strongly support any effort to avoid the loss of possible acceptable lungs. In particular, previous major cardiac surgery does not strictly imply a poor quality of lungs as well as unsustainable graft procurement.

PMID: 28457372 [PubMed - in process]

Lobar Lung Transplantation From Deceased Donor: Monocentric Experience.

Transplant Proc. 2017 May;49(4):682-685

Authors: Mendogni P, Palleschi A, Tosi D, Righi I, Montoli M, Damarco F, Morlacchi LC, Santambrogio L, Nosotti M, Rosso L

Abstract
INTRODUCTION: Lung transplantation is considered a therapeutic option in selected patients affected by end-stage pulmonary disease. The mortality on the waiting list is mainly attributed to the shortage of the donor pool available for transplantation. There are various strategies to overcome this shortage; one of them is lobar transplantation.
METHODS: The aim of the current study was to analyze the outcome of lobar lung transplantation from deceased donors in our Lung Transplant Center. Overall survival, perioperative mortality and morbidity, problem on bronchial anastomosis, and chronic rejection were prospectively recorded in a 5-year time-frame.
RESULTS: From November 2010 to October 2015, we performed 100 lung transplantations; 6 of which (6%) were lobar transplantations from deceased donors. Three recipients were on an emergency list due to preoperative extracorporeal support. The causes of lobectomy leading to lobar transplantation were: size mismatch (3), iatrogenic vascular damage (2), and chronic atelectasis (1). One patient died 5 months after surgery for sepsis; and 5 patients were alive at the study end (median follow-up: 17.5 months). Prevalence of grade 3 primary graft dysfunction at 72 hours was 50%. One patient developed bronchial stenosis. No cases of chronic rejection were recorded.
CONCLUSIONS: Lobar transplantation can be considered a valid tool to overcome the donor pool shortage in selected cases; such a technique has proved particularly useful in critically ill patients who were scheduled in an emergency transplant program.

PMID: 28457371 [PubMed - in process]

Increased risk of PTLD in lung transplant recipients with cystic fibrosis.

J Cyst Fibros. 2017 Apr 26;:

Authors: Lowery EM, Adams W, Grim SA, Clark NM, Edwards L, Layden JE

Abstract
BACKGROUND: Post-transplant lymphoproliferative disease (PTLD) is an important cause of morbidity and mortality following lung transplantation. Recipients with cystic fibrosis (CF) may have an increased risk of PTLD although the literature is limited to single center cohorts. Our primary aim is to examine PTLD in an adult lung transplant population by utilizing the International Society for Heart and Lung Transplantation Registry.
METHODS: We studied 30,598 adult recipients of lung transplants performed between 1999 and 2011. The primary outcome was development of and time to PTLD. In addition to indication for transplant, other predictors examined included Epstein-Barr virus (EBV) and cytomegalovirus (CMV) serostatus, gender, and age. Outcomes were assessed with univariable and multivariable Cox proportional hazard models to obtain hazard ratios (HR).
RESULTS: 17% of the cohort had a diagnosis of CF. PTLD developed in 2% of CF recipients compared to 1% for non-CF recipients (p<0.001). Compared to non-CF recipients, CF recipients had higher prevalence of EBV and CMV seronegativity and higher prevalences of high risk EBV and CMV mismatch (D+/R-). There is a significant association between CF and the development of PTLD [HR 1.66 (95% CI 1.30-2.12)]. Stratified multivariable analysis controlling for age revealed EBV negative non-CF recipients have an almost 2 fold increased risk of developing PTLD, whereas EBV negative CF recipients had an almost 6.5 fold increased risk.
CONCLUSIONS: CF recipients have a higher risk for PTLD compared to non-CF recipients. Further studies are needed to account for additional risk factors and management in this population post-transplant.

PMID: 28456611 [PubMed - as supplied by publisher]

CFTR gene mutations and polymorphism are associated with non-obstructive azoospermia: From case-control study.

Gene. 2017 Apr 26;:

Authors: Jiang L, Jin J, Wang S, Zhang F, Dai Y, Shi L, Zhang S

Abstract
A variety of experimental studies have yielded evidence that the cystic fibrosis transmembrane conductance regulator (CFTR) protein participates in the process of spermatogenesis. However, the association between CFTR gene and non-obstructive azoospermia (NOA) disease remained to be a question. First, we reviewed available data from the PubMed and Embase databases before May 2016 to find the most common mutations of CFTR gene in NOA patients. Second, an original case-control study was conducted on NOA patients (n=100) and a control group consisting of fertile males (n=100), selected from August 2015 to March 2017, to detect CFTR gene mutations and polymorphism. Peripheral blood samples from NOA patients and normal controls were analyzed for the presence of specific sequences of CFTR gene by polymerase chain reaction amplification followed by direct sequencing. From our comprehensive review, 12 case-control studies were found concerning the relation between CFTR gene mutations and polymorphism and NOA disease. Fifty-four mutations were mentioned and IVS8 poly-T, TG repeats, F508del and R117H mutations were the most common ones. Based on that, we detected IVS8 poly-T, TG repeats, F508del, R117H and M470V mutations in our case control study. We found that the T5 allele was present at a significantly higher rate in NOA patients than in the control group (5.00% versus 0.00%, p<0.01) with increased risk having NOA [Odds ratios (OR) 2.05, 95% confidence intervals (CI) 1.85-2.27]. The T5 variant was always accompanied by TG12 (10/10) and V470 allele participated in most TG12T5 haplotypes (8/10). TG12T5-V470 haplotype also enhanced risk of having NOA [OR 2.04, 95% CI 1.84-2.26]. F508del and R117H mutations were not found in either group. In conclusion, the polyvariant mutant genes of CFTR: T5 allele and TG12-T5-V470 genotype are correlated with NOA, but F508del and R117H mutations have low possibility to be associated with NOA.

PMID: 28456595 [PubMed - as supplied by publisher]

Corrigendum to "Plasma metabolomics in adults with cystic fibrosis during a pulmonary exacerbation: A pilot randomized study of high-dose vitamin D3 administration" [Metabolism vol. 70, May 2017, pages 31-41].

Metabolism. 2017 Apr 26;:

Authors: Alvarez JA, Chong EY, Walker DI, Chandler JD, Michalski ES, Grossmann RE, Uppal K, Li S, Frediani JK, Tirouvanziam R, Tran VT, Tangpricha V, Jones DP, Ziegler TR

PMID: 28456337 [PubMed - as supplied by publisher]

Hypertonic Saline as a Useful Tool for Sputum Induction and Pathogen Detection in Cystic Fibrosis.

Lung. 2017 Apr 28;:

Authors: Ferreira ACM, Marson FAL, Cohen MA, Bertuzzo CS, Levy CE, Ribeiro AF, Ribeiro JD

Abstract
PURPOSE: The aim of this study was to compare the qualitative and semi-quantitative detection of pathogens in the airway secretions of patients with cystic fibrosis (CF) and the sputum induction capacity before and after inhalation of 7% hypertonic saline solution (HSS).
METHODS: The study enrolled 64 patients with CF. Airway secretions were collected from all enrolled patients with CF before and after inhalation of 7% HSS, and the samples were screened for pathogens.
RESULTS: Inhalation of 7% HSS increased the probability of producing sputum from 36 to 52% (p = 0.002) in children with CF. The effect was most in children under 11 years. Inhalation of 7% HSS improved qualitative pathogen identification (p = 0.008). Inhalation of 7% HSS increased the mucoid Pseudomonas aeruginosa (p = 0.002) and non-mucoid P. aeruginosa in the semi-quantitative analysis (p = 0.035). Four new pathogens (Aspergillus fumigatus, Achromobacter xylosoxidans, Ochrobactrum anthropi, and Elizabethkingia meningoseptica) were identified in the sputum samples collected from the airways of patients with CF following 7% HSS.
CONCLUSIONS: Inhalation of 7% HSS increased sputum production and pathogen identification in children with CF. The inhalation of 7% HSS was feasible and should be implemented for routine pathogen detection in the airways of patients with CF, particularly in those patients who do not produce sputum.

PMID: 28455785 [PubMed - as supplied by publisher]

Macrophage Dysfunction in Respiratory Disease.

Results Probl Cell Differ. 2017;62:299-313

Authors: Belchamber KBR, Donnelly LE

Abstract
In the healthy lung, macrophages maintain homeostasis by clearing inhaled particles, bacteria, and removing apoptotic cells from the local pulmonary environment. However, in respiratory diseases including chronic obstructive pulmonary disease (COPD), asthma, and cystic fibrosis, macrophages appear to be dysfunctional and may contribute to disease pathogenesis. In COPD, phagocytosis of bacterial species and apoptotic cells by both alveolar macrophages and monocyte-derived macrophages is significantly reduced, leading to colonization of the lung with pathogenic bacteria. COPD macrophages also release high levels of pro-inflammatory cytokines and chemokines, including CXCL8, TGFβ, and CCL2, driving recruitment of other inflammatory cells including neutrophils and monocytes to the lungs and promoting disease progression.In asthma, defective phagocytosis and efferocytosis have also been reported, and macrophages appear to have altered cell surface receptor expression; however, it is as yet unclear how this contributes to disease progression but may be important in driving Th2-mediated inflammation. In cystic fibrosis, macrophages also display defective phagocytosis, and reduced bacterial killing, which may be driven by the pro-inflammatory environment present in the lungs of these patients.The mechanisms behind defective macrophage function in lung diseases are not currently understood, but potential mechanisms include alterations in phagocytic receptor expression levels, oxidative stress, but also the possibility that specific diseases are associated with a specific, altered, macrophage phenotype that displays reduced function. Identification of the mechanisms responsible may present novel therapeutic opportunities for treatment.

PMID: 28455714 [PubMed - in process]

Protocol of a Pilot Study of Technology-Enabled Coproduction in Pediatric Chronic Illness Care.

JMIR Res Protoc. 2017 Apr 28;6(4):e71

Authors: Kaplan HC, Thakkar SN, Burns L, Chini B, Dykes DM, McPhail GL, Moore E, Saeed SA, Eslick I, Margolis PA, Opipari-Arrigan L

Abstract
BACKGROUND: Pediatric chronic illness care models are traditionally organized around acute episodes of care and may not meet the needs of patients and their families. Interventions that extend the patient-clinician interaction beyond the health care visit, allow for asynchronous and bidirectional feedback loops that span visits and daily life, and facilitate seamless sharing of information are needed to support a care delivery system that is more collaborative, continuous, and data-driven. Orchestra is a mobile health technology platform and intervention designed to transform the management of chronic diseases by optimizing patient-clinician coproduction of care.
OBJECTIVE: The aim of this study is to assess the feasibility, acceptability, and preliminary impact of the Orchestra technology and intervention in the context of pediatric chronic illness care.
METHODS: This study will be conducted in the cystic fibrosis and inflammatory bowel disease clinics at Cincinnati Children's Hospital Medical Center. We will enroll interested patients and their caregivers to work with clinicians to use the Orchestra technology platform and care model over a 6-month period. In parallel, we will use quality improvement methods to improve processes for integrating Orchestra into clinic workflows and patient/family lifestyles. We will use surveys, interviews, technology use data, and measures of clinical outcomes to assess the feasibility, acceptability, and preliminary impact of Orchestra. Outcome measures will include assessments of: (1) enrollment and dropout rates; (2) duration of engagement/sustained use; (3) symptom and patient-reported outcome tracker completion rates; (4) perceived impact on treatment plan, communication with the clinical team, visit preparation, and overall care; (5) changes in disease self-efficacy and engagement in care; and (6) clinical outcomes and health care utilization.
RESULTS: Participant recruitment began in mid-2015, with results expected in 2017.
CONCLUSIONS: Chronic disease management needs a dramatic transformation to support more collaborative, effective, and patient-centered care. This study is unique in that it is testing not only the impact of technology, but also the necessary processes that facilitate patient and clinician collaboration. This pilot study is designed to examine how technology-enabled coproduction can be implemented in real-life clinical contexts. Once the Orchestra technology and intervention are optimized to ensure feasibility and acceptability, future studies can test the effectiveness of this approach to improve patient outcomes and health care value.

PMID: 28455274 [PubMed - in process]

Bronchoprotective mechanisms for specialized pro-resolving mediators in the resolution of lung inflammation.

Mol Aspects Med. 2017 Apr 25;:

Authors: Duvall MG, Bruggemann TR, Levy BD

Abstract
Bronchi are exposed daily to irritants, microbes and allergens as well as extremes of temperature and acid. The airway mucosal epithelium plays a pivotal role as a sentinel, releasing alarmins when danger is encountered. To maintain homeostasis, an elaborate counter-regulatory network of signals and cellular effector mechanisms are needed. Specialized pro-resolving mediators (SPMs) are chemical mediators that enact resolution programs in response to injury, infection or allergy. SPMs are enzymatically derived from essential polyunsaturated fatty acids with potent cell-type specific immunoresolvent properties. SPMs signal by engaging cell-based receptors to turn off acute inflammatory responses and restore tissue homeostasis. Several common lung diseases involving the airways, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF), are characterized by unresolved bronchial inflammation. In preclinical murine models of lung disease, SPMs carry potent bronchoprotective actions. Here, we review cellular and molecular effects for SPM-initiated catabasis in the lung and their human translation.

PMID: 28455109 [PubMed - as supplied by publisher]

Optimization of the French cystic fibrosis newborn screening programme by a centralized tracking process.

J Med Screen. 2017 Jan 01;:969141317692611

Authors: Munck A, Delmas D, Audrézet MP, Lemonnier L, Cheillan D, Roussey M

Abstract
Objectives To evaluate the French cystic fibrosis newborn screening algorithm, based on data tracked by a centralized monitoring process, from 2002 to 2014. The programme aimed to attain European Standards in terms of positive predictive value, sensitivity, the ratio of screen positive patients diagnosed with cystic fibrosis to infants who screen positive but with inconclusive diagnosis (CFSPID), and time to diagnosis. Methods Retrospective analysis of programme performance, compliance with the algorithm, and changes in screening strategy. Results Modifications in the flow chart protocol improved the positive predictive value to 0.31 while maintaining the sensitivity at 0.95. Among infants diagnosed with cystic fibrosis, or identified as CFSPID, sweat test results were obtained for 94%, and two mutations were identified after exhaustive screening for the gene, when applicable, in 99.6%. The rate of pending diagnosis was very low (0.5%). The ratio of infants with cystic fibrosis:CFSPID was 6.3:1. Age at initial visit at the CF centre was ≤ 35 days, respectively, in 53%/26%. Conclusion Performances were in agreement with European standards, but timeliness of initial visit needed improvement. Our data complement an accumulating body of evidence demonstrating that attention must be paid to such ethical considerations as limiting carrier detection and inconclusive diagnosis. Newborn screening programmes should have a rigorous centralized monitoring process to warrant adjustments for improving performance to attain consensus guidelines.

PMID: 28454512 [PubMed - as supplied by publisher]

Does a checklist reduce the number of errors made in nurse-assembled discharge prescriptions?

Br J Nurs. 2017 Apr 27;26(8):464-467

Authors: Byrne C, Sierra H, Tolhurst R

Abstract
BACKGROUND: The safe supply of medicines is an integral part of being discharged from hospital. Locally, nurses are responsible for assembling medication for discharge prescriptions. Over a 2-year period 15 serious medication errors relating to discharge were reported on the health and ageing unit. This project was designed to evaluate whether a discharge medication checklist could reduce errors on nurse-assembled discharge prescriptions.
METHODS AND RESULTS: A baseline audit was conducted to identify the number of medication errors on nurse-assembled discharge prescriptions. After the audit period the discharge medication checklist was introduced and education and training was provided to nursing staff. There was a statistically significant reduction in the number of assembled discharge prescriptions with one or more errors (28/56 vs. 9/44; p=0.0478) when re-audited.
CONCLUSION: The introduction of a discharge medication checklist demonstrated a significant reduction in errors. The authors recommend that the discharge medication checklist and training programme be rolled out across medical wards to facilitate safe discharge.

PMID: 28453319 [PubMed - in process]

[EXPERIMENTAL MODEL AND CURRENCY OF EXPERIMENT OF DISTANT RESULTS OF LEAD EXPOSITION].

Georgian Med News. 2017 Feb;(263):125-129

Authors: Pataraia G, Bagashvili T, Andronikashvili G, Gurashvili T, Gogeshvili K, Avalishvili M

Abstract
In order to explore the distant results of exposition of little doses of lead, for the objective of the experiment model we have selected 32 mongral rats, of different age, but aged of both sex. Experimental animals were divided in two groups. During first two month from the beginning of the experiment, together with permissible food, animals were given the water, in which was open Pb(NO3)2 - to first group 1.5 mg on kg/weight and to II group 15 mg on kg/weight during the day and night. Before the beginning of the experiment, in the time of process and after it, observation was conducted, description and collection of photo-video materials about the behavior of animals, physiological parameters, possible change of weight, clear-sighted changes in appearance. During the autopsy of the animal, died during the experiment, it turned out that the reason of the death was acute heart failure caused by septicopyemia, the bilateral abscess pneumonia and right sided purulent pleurisy. The reason of the death of second animal was DIC (disseminated intravascular coagulation) Syndrome and the polyorganic pathology caused by it. We made the Nembutal injection to third animal because there was detected the 50×40×20 sized subcutaneous formation on the right surface of the chest, that turned out to be the breast adenoma with cystic fibrosis. After the completion of the experiment of distant results of lead exposition, surviving rats before autopsy will be dropped to sleep with high dose of drugs in compliance with the "Guidelines of animal care and ethical behavior", taken material will be processed for histopathological (in case of necessity histochemical and imunomorphological) and electronic microscopic researches.

PMID: 28452739 [PubMed - in process]

Respiratory viral detection in the paranasal sinuses of patients with cystic fibrosis.

Am J Rhinol Allergy. 2017 Mar 01;31(2):105-108

Authors: Rowan NR, Wang EW, Kanaan A, Sahu N, Williams JV, Phillips CD, Lee SE

Abstract
BACKGROUND: Pulmonary colonization with antibiotic-resistant organisms in patients with cystic fibrosis (CF) is often preceded by upper-airway infections. Although there is a well-described relationship between pulmonary respiratory viral infections and overall disease progression of CF, the pathogenicity of respiratory viral infections in the paranasal sinuses of patients with CF remains unknown. With recent advances in respiratory virus detection techniques, this study sought to detect the presence of respiratory viruses in the paranasal sinuses of patients with CF in comparison with healthy controls and to correlate the viral presence with clinical measures of sinonasal disease.
METHODS: This prospective individual cohort study compared 24 patients with CF with 14 healthy controls. Basic demographics, clinical measures of disease and respiratory viral screens (commercial multiplex) obtained directly from the paranasal sinuses were compared between the two groups.
RESULTS: Respiratory viruses were detected in 33% of patients with CF (8/24) compared with 0% of the healthy controls (0/14) (p = 0.017). Respiratory viruses were only detected during the winter months, and the most commonly identified were influenza A and human rhinovirus strains. There was no statistical difference in the 22-Item Sino-Nasal Outcome Test (SNOT-22) scores (p = 0.93) or modified Lund-Kennedy scores (p = 0.74) between patients with CF with a positive viral test and those without a positive result.
CONCLUSIONS: Respiratory viral detection is more commonly detected in the paranasal sinuses of patients with CF compared with healthy controls. Although respiratory viral presence did not correlate with a worse clinical severity of sinonasal disease, these findings may provide insight into the pathophysiology of CF and open new avenues for potential targeted therapy.

PMID: 28452706 [PubMed - in process]