Treatment of human airway epithelial Calu-3 cells with a peptide-nucleic acid (PNA) targeting the microRNA miR-101-3p is associated with increased expression of the cystic fibrosis Transmembrane Conductance Regulator () gene.

Eur J Med Chem. 2020 Oct 02;:112876

Authors: Fabbri E, Tamanini A, Jakova T, Gasparello J, Manicardi A, Corradini R, Finotti A, Borgatti M, Lampronti I, Munari S, Dechecchi MC, Cabrini G, Gambari R

Abstract
Since the identification of microRNAs (miRNAs) involved in the regulation of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, miRNAs known to down-regulate the expression of the CFTR and associated proteins have been investigated as potential therapeutic targets. Here we show that miR-101-3p, targeting the 3'-UTR sequence of the CFTR mRNA, can be selectively inhibited by a peptide nucleic acid (PNA) carrying a full complementary sequence. With respect to clinical relevance of microRNA targeting, it is expected that reduction in concentration of miRNAs (the anti-miRNA approach) could be associated with increasing amounts of target mRNAs. Consistently to this hypothesis, we report that PNA-mediated inhibition of miR-101-3p was accompanied by CFTR up-regulation. Next Generation Sequencing (NGS) was performed in order to verify the effects of the anti-miR-101-3p PNA on the Calu-3 miRNome. Upon inhibition of miR-101-3p we observed a fold change (FC) expression <2 of the majority of miRNAs (403/479, 84.13%), whereas we identified a list of dysregulated miRNAs, suggesting that specific miRNA inhibition (in our case miR-101-3p) might be accompanied by alteration of expression of other miRNAs, some of them known to be involved in Cystic Fibrosis (CF), such as miR-155-5p and miR-125b-5p.

PMID: 33127171 [PubMed - as supplied by publisher]

New strategies of physical activity assessment in cystic fibrosis: a pilot study.

BMC Pulm Med. 2020 Oct 30;20(1):285

Authors: Savi D, Graziano L, Giordani B, Schiavetto S, Vito C, Migliara G, Simmonds NJ, Palange P, Elborn JS

Abstract
BACKGROUND: Regular physical activity (PA) is a valued part of cystic fibrosis (CF) care. Although the accelerometer, SenseWear Armband (SWA), accurately measures habitual PA in CF, it is mostly used for research purposes. For the first time, we analyzed different methods of measuring PA in daily life by the use of smartphones and other electronic devices such as smartwatch and Fitbit.
METHODS: Twenty-four stable adults with CF (mean age 37.5 ± 11.5SD yrs.; FEV1 58 ± 19% predicted, BMI 22.9 ± 3.2) were studied. Daily PA was monitored for seven consecutive days. All patients wore the accelerometer SWA and at the same time they monitored PA with the electronic device they used routinely. They were allocated into one of four arms according to their device: Smartwatch, Fitbit, Android smartphones and iOS smartphones. PA related measurements included: duration of PA, energy expenditure, number of steps.
RESULTS: There was a good agreement between SWA and Fitbit for number of steps (p = 0.605) and energy expenditure (p = 0.143). iOS smartphones were similar to SWA in monitoring the number of steps (p = 0.911). Significant differences were found between SWA and both Smartwatch and Android smartphones.
CONCLUSIONS: Fitbit and iOS smartphones seem to be a valuable approach to monitor daily PA. They provide a good performance to measure step number compared to SWA.

PMID: 33126875 [PubMed - as supplied by publisher]

Characterization of Myocardial Injury in Patients With COVID-19.

J Am Coll Cardiol. 2020 Nov 03;76(18):2043-2055

Authors: Giustino G, Croft LB, Stefanini GG, Bragato R, Silbiger JJ, Vicenzi M, Danilov T, Kukar N, Shaban N, Kini A, Camaj A, Bienstock SW, Rashed ER, Rahman K, Oates CP, Buckley S, Elbaum LS, Arkonac D, Fiter R, Singh R, Li E, Razuk V, Robinson SE, Miller M, Bier B, Donghi V, Pisaniello M, Mantovani R, Pinto G, Rota I, Baggio S, Chiarito M, Fazzari F, Cusmano I, Curzi M, Ro R, Malick W, Kamran M, Kohli-Seth R, Bassily-Marcus AM, Neibart E, Serrao G, Perk G, Mancini D, Reddy VY, Pinney SP, Dangas G, Blasi F, Sharma SK, Mehran R, Condorelli G, Stone GW, Fuster V, Lerakis S, Goldman ME

Abstract
BACKGROUND: Myocardial injury is frequent among patients hospitalized with coronavirus disease-2019 (COVID-19) and is associated with a poor prognosis. However, the mechanisms of myocardial injury remain unclear and prior studies have not reported cardiovascular imaging data.
OBJECTIVES: This study sought to characterize the echocardiographic abnormalities associated with myocardial injury and their prognostic impact in patients with COVID-19.
METHODS: We conducted an international, multicenter cohort study including 7 hospitals in New York City and Milan of hospitalized patients with laboratory-confirmed COVID-19 who had undergone transthoracic echocardiographic (TTE) and electrocardiographic evaluation during their index hospitalization. Myocardial injury was defined as any elevation in cardiac troponin at the time of clinical presentation or during the hospitalization.
RESULTS: A total of 305 patients were included. Mean age was 63 years and 205 patients (67.2%) were male. Overall, myocardial injury was observed in 190 patients (62.3%). Compared with patients without myocardial injury, those with myocardial injury had more electrocardiographic abnormalities, higher inflammatory biomarkers and an increased prevalence of major echocardiographic abnormalities that included left ventricular wall motion abnormalities, global left ventricular dysfunction, left ventricular diastolic dysfunction grade II or III, right ventricular dysfunction and pericardial effusions. Rates of in-hospital mortality were 5.2%, 18.6%, and 31.7% in patients without myocardial injury, with myocardial injury without TTE abnormalities, and with myocardial injury and TTE abnormalities. Following multivariable adjustment, myocardial injury with TTE abnormalities was associated with higher risk of death but not myocardial injury without TTE abnormalities.
CONCLUSIONS: Among patients with COVID-19 who underwent TTE, cardiac structural abnormalities were present in nearly two-thirds of patients with myocardial injury. Myocardial injury was associated with increased in-hospital mortality particularly if echocardiographic abnormalities were present.

PMID: 33121710 [PubMed - in process]

Characterising the respiratory microbiome.

Eur Respir J. 2019 02;53(2):

Authors: Watson RL, de Koff EM, Bogaert D

PMID: 30487204 [PubMed - indexed for MEDLINE]

Autoimmunity to bactericidal/permeability-increasing protein in bronchiectasis exhibits a requirement for Pseudomonas aeruginosa IgG response.

Eur Respir J. 2019 02;53(2):

Authors: Skopelja-Gardner S, Theprungsirikul J, Meagher RE, Beliveau CM, Bradley KE, Avery M, Henkle E, Siegel S, Gifford AH, Winthrop KL, Rigby WFC

PMID: 30385530 [PubMed - indexed for MEDLINE]

17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2020/10/31

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Cystic Fibrosis"

These pubmed results were generated on 2020/10/30

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Strategies for cystic fibrosis transmembrane conductance regulator inhibition: from molecular mechanisms to treatment for secretory diarrhoeas.

FEBS Lett. 2020 Oct 28;:

Authors: de Jonge HR, Ardelean MC, Bijvelds MJ, Vergani P

Abstract
Cystic fibrosis transmembrane conductance regulator (CFTR) is an unusual ABC transporter. It acts as an anion-selective channel that drives osmotic fluid transport across many epithelia. In the gut, CFTR is crucial for maintaining fluid and acid-base homeostasis, and its activity is tightly controlled by multiple neuro-endocrine factors. However, microbial toxins can disrupt this intricate control mechanism and trigger protracted activation of CFTR. This results in the massive faecal water loss, metabolic acidosis and dehydration that characterise secretory diarrhoeas, a major cause of malnutrition and death of children under 5 years of age. Compounds that inhibit CFTR could improve emergency treatment of diarrhoeal disease. Drawing on recent structural and functional insight, we discuss how existing CFTR inhibitors function at the molecular and cellular level. We compare their mechanisms of action to those of inhibitors of related ABC transporters, revealing some unexpected features of drug action on CFTR. Although challenges remain, especially relating to the practical effectiveness of currently available CFTR inhibitors, we discuss how recent technological advances might help develop therapies to better address this important global health need.

PMID: 33113586 [PubMed - as supplied by publisher]

Getting Near to "Closing the gap" in the Pediatric Age-group for First Personalized Treatment of Cystic Fibrosis.

Am J Respir Crit Care Med. 2020 Oct 28;:

Authors: van Koningsbruggen-Rietschel S

PMID: 33113333 [PubMed - as supplied by publisher]

Clinical impact of respiratory virus in pulmonary exacerbations of children with Cystic Fibrosis.

PLoS One. 2020;15(10):e0240452

Authors: Meyer VMC, Siqueira MM, Costa PFBM, Caetano BC, Oliveira Lopes JC, Folescu TW, Motta FDC

Abstract
BACKGROUNDS: Cystic Fibrosis (CF) is a genetic, multisystemic, progressive illness that causes chronic suppurative lung disease. A major cause of morbimortality in this condition are pulmonary exacerbations. Although classically attributed to bacterial infections, respiratory virus have been increasingly recognized in its ethiopathogeny.
METHODS: Nasopharyngeal swab samples were collected from children < 18 years old with CF in Rio de Janeiro, Brazil, with pulmonary exacerbation criteria. Samples were submitted to RT-PCR for Adenovirus, Influenza A and B, Parainfluenza Virus, Respiratory Syncytial Virus (RSV), Metapneumovirus and Rhinovirus. Virus positive and virus negative groups were compared in regards to clinical presentation, severity of exacerbation and bacterial colonization.
RESULTS: Out of 70 samples collected from 48 patients, 35.7% were positive for respiratory viruses. Rhinovirus were the most common (28% of all positive samples), followed by RSV. The virus positive group was associated with change in sinus discharge (p = 0.03). Considering only patients younger than five years old, positive virus detection was also associated with fever (p = 0.01). There was no significant difference in clinical severity or in bacterial colonization between virus positive and negative groups.
CONCLUSIONS: Prospective studies are still needed to assess the long term impact of viral infections in patients with CF, and their interaction with the bacterial microbiome in these patients.

PMID: 33112873 [PubMed - as supplied by publisher]

The first five-year evaluation of cystic fibrosis neonatal screening program in São Paulo State, Brazil.

Cad Saude Publica. 2020;36(10):e00049719

Authors: Maciel LMZ, Magalhães PKR, Ciampo IRLD, Sousa MLB, Fernandes MIM, Sawamura R, Bittar RR, Molfetta GA, Silva Júnior WAD

Abstract
The Hospital of the Ribeirão Preto Medical School, University of São Paulo is one of the three screening centers in São Paulo State, Brazil, and has included a test for cystic fibrosis (CF) since February 6, 2010, by a court order. We evaluated the first five years of this CF-newborn screening program. The original immunoreactive trypsinogen (IRT)/IRT screening protocol was adopted in Brazil. A total of 173,571 newborns were screened, 1,922 (1.1%) of whom showed IRT1 ≥ 70ng/mL. Of these, 1,795 (93.4%) collected IRT2, with elevated results (IRT2 ≥ 70ng/mL) in 102 of them (5.2%). We identified a total of 26 CF cases during this period, including three CF cases that were not detected by the CF-newborn screening. The incidence of the disease among the screened babies was 1:6,675 newborns screened. Median age at the initial evaluation was 42 days, comparable to that of neonates screened with the IRT/DNA protocol. Almost all infants with CF already exhibited some manifestations of the disease during the neonatal period. The mutation most frequently detected in the CF cases was F508del. These findings suggest the early age at the beginning of treatment at our center was due to the effort of the persons involved in the program regarding an effective active search. Considering the false negative results of CF-newborn screening and the early onset of clinical manifestations of the disease in this study, pediatricians should be aware of the diagnosis of CF even in children with negative test.

PMID: 33111836 [PubMed - in process]

Protocol for Application, Standardization and Validation of the Forskolin-Induced Swelling Assay in Cystic Fibrosis Human Colon Organoids.

STAR Protoc. 2020 Jun 19;1(1):100019

Authors: Vonk AM, van Mourik P, Ramalho AS, Silva IAL, Statia M, Kruisselbrink E, Suen SWF, Dekkers JF, Vleggaar FP, Houwen RHJ, Mullenders J, Boj SF, Vries R, Amaral MD, de Boeck K, van der Ent CK, Beekman JM

Abstract
This protocol describes the isolation, handling, culture of, and experiments with human colon stem cell organoids in the context of cystic fibrosis (CF). In human colon organoids, the function of cystic fibrosis transmembrane conductance regulator (CFTR) protein and its rescue by CFTR modulators can be quantified using the forskolin-induced swelling assay. Implementation procedures and validation experiments are described for six CF human colon organoid lines, and representative CFTR genotypes are tested for basal CFTR function and response to CFTR-modulating drugs. For complete details on the use and execution of this protocol, please refer to Dekkers et al (2016) and Berkers and van Mourik (2019).

PMID: 33111074 [PubMed]

Gene Loss and Acquisition in Lineages of Pseudomonas aeruginosa Evolving in Cystic Fibrosis Patient Airways.

mBio. 2020 Oct 27;11(5):

Authors: Gabrielaite M, Johansen HK, Molin S, Nielsen FC, Marvig RL

Abstract
Genome analyses have documented that there are differences in gene repertoire between evolutionary distant lineages of the same bacterial species; however, less is known about microevolutionary dynamics of gene loss and acquisition within bacterial lineages as they evolve over years. Here, we analyzed the genomes of 45 Pseudomonas aeruginosa lineages evolving in the lungs of cystic fibrosis (CF) patients to identify genes that are lost or acquired during the first years of infection. On average, lineage genome content changed by 88 genes (range, 0 to 473). Genes were more often lost than acquired, and prophage genes were more variable than bacterial genes. We identified convergent loss or acquisition of the same genes across lineages, suggesting selection for loss and acquisition of certain genes in the host environment. We found that a notable proportion of such genes are associated with virulence; a trait previously shown to be important for adaptation. Furthermore, we also compared the genomes across lineages to show that the within-lineage variable genes (i.e., genes that had been lost or acquired during the infection) often belonged to genomic content not shared across all lineages. In sum, our analysis adds to the knowledge on the pace and drivers of gene loss and acquisition in bacteria evolving over years in a human host environment and provides a basis to further understand how gene loss and acquisition play roles in lineage differentiation and host adaptation.IMPORTANCE Bacterial airway infections, predominantly caused by P. aeruginosa, are a major cause of mortality and morbidity of CF patients. While short insertions and deletions as well as point mutations occurring during infection are well studied, there is a lack of understanding of how gene loss and acquisition play roles in bacterial adaptation to the human airways. Here, we investigated P. aeruginosa within-host evolution with regard to gene loss and acquisition. We show that during long-term infection P. aeruginosa genomes tend to lose genes, in particular, genes related to virulence. This adaptive strategy allows reduction of the genome size and evasion of the host's immune response. This knowledge is crucial to understand the basic mutational steps that, on the timescale of years, diversify lineages and adds to the identification of bacterial genetic determinants that have implications for CF disease.

PMID: 33109761 [PubMed - in process]

Feasibility study for supporting medication adherence for adults with cystic fibrosis: mixed-methods process evaluation.

BMJ Open. 2020 Oct 27;10(10):e039089

Authors: Hind D, Drabble SJ, Arden MA, Mandefield L, Waterhouse S, Maguire C, Cantrill H, Robinson L, Beever D, Scott A, Keating S, Hutchings M, Bradley J, Nightingale J, Allenby MI, Dewar J, Whelan P, Ainsworth J, Walters SJ, Wildman MJ, O'Cathain A

Abstract
OBJECTIVES: To undertake a process evaluation of an adherence support intervention for people with cystic fibrosis (PWCF), to assess its feasibility and acceptability.
SETTING: Two UK cystic fibrosis (CF) units.
PARTICIPANTS: Fourteen adult PWCF; three professionals delivering adherence support ('interventionists'); five multi-disciplinary CF team members.
INTERVENTIONS: Nebuliser with data recording and transfer capability, linked to a software platform, and strategies to support adherence to nebulised treatments facilitated by interventionists over 5 months (± 1 month).
PRIMARY AND SECONDARY MEASURES: Feasibility and acceptability of the intervention, assessed through semistructured interviews, questionnaires, fidelity assessments and click analytics.
RESULTS: Interventionists were complimentary about the intervention and training. Key barriers to intervention feasibility and acceptability were identified. Interventionists had difficulty finding clinic space and time in normal working hours to conduct review visits. As a result, fewer than expected intervention visits were conducted and interviews indicated this may explain low adherence in some intervention arm participants. Adherence levels appeared to be >100% for some patients, due to inaccurate prescription data, particularly in patients with complex treatment regimens. Flatlines in adherence data at the start of the study were linked to device connectivity problems. Content and delivery quality fidelity were 100% and 60%-92%, respectively, indicating that interventionists needed to focus more on intervention 'active ingredients' during sessions.
CONCLUSIONS: The process evaluation led to 14 key changes to intervention procedures to overcome barriers to intervention success. With the identified changes, it is feasible and acceptable to support medication adherence with this intervention.
TRIAL REGISTRATION NUMBER: ISRCTN13076797; Results.

PMID: 33109661 [PubMed - in process]

Association for European Paediatric and Congenital Cardiology recommendations for basic training in paediatric and congenital cardiology 2020.

Cardiol Young. 2020 Oct 28;:1-16

Authors: Heying R, Albert DC, Voges I, Sendzikaite S, Sarquella-Brugada G, Pluchinotta F, Brzezinska-Rajszys G, Stein JI, Milanesi O

Abstract
The recommendations of the Association for European Paediatric and Congenital Cardiology for basic training in paediatric and congenital cardiology required to be recognised as a paediatric cardiologist by the Association for European Paediatric and Congenital Cardiology are described below. Those wishing to achieve more advanced training in particular areas of paediatric cardiology should consult the training recommendations of the different Association for European Paediatric and Congenital Cardiology Working Groups available on the Association for European Paediatric and Congenital Cardiology website (www.aepc.org) and the respective publications 1-6. The development of training requirements is the responsibility of the Educational Committee and the Association for European Paediatric and Congenital Cardiology Council in collaboration with the Working Groups of the Association for European Paediatric and Congenital Cardiology. Trainees should be exposed to all aspects of general paediatric and congenital cardiology from fetal life to adolescence and adulthood. Centres performing generalised and specialised work in paediatric and congenital cardiology should be committed to deliver postgraduate training. At each training institute, trainers should be appointed to supervise and act as mentors to the trainees. Association for European Paediatric and Congenital Cardiology will provide basic teaching courses to supplement the training process.

PMID: 33109300 [PubMed - as supplied by publisher]

Use of medical marijuana in cystic fibrosis patients.

BMC Complement Med Ther. 2020 Oct 27;20(1):323

Authors: Stephen MJ, Chowdhury J, Tejada LA, Zanni R, Hadjiliadis D

Abstract
BACKGROUND: The usage and attitudes towards medical marijuana in Cystic Fibrosis (CF) patients is unknown. Through the use of a survey we aim to clarify rates and reasons for use.
METHODS: An anonymous survey was sent out to six centers in the Mid-Atlantic region of the United States. Use of and reason for medical marijuana was assessed, along with attitudes of the perceived utility of medical marijuana.
RESULTS: A total of 637 surveys were sent out, and 193 surveys were returned (30.3% return rate). Three did not give consent, and one was empty, for a total of 189 completed surveys. 31 subjects (16.5%) reported having used marijuana for medical purposes in their lifetime, with 29 (15.4%) of these in the past year. The most used forms were edible and vaporized. The most common indications for usage were pain and stress. 28 out of 31 found marijuana to be a great deal effective for their symptoms. 21 of the 31 rated marijuana very important or important to their health. There were two reported side effects, both mild. Of 156 subjects who responded to the question if they would be interested in medical marijuana if available, 72 (46.2%) replied yes.
CONCLUSION: The use of marijuana for medical reasons was 15.4% in the past year in this sample CF population, although more expressed interest if it was available through prescription. Side effects were rare. CF physicians are going to have to familiarize themselves with advantages and disadvantages of medical marijuana as there is a great deal of interest within the community, and legalization becomes more common.

PMID: 33109153 [PubMed - in process]

Neutrophil extracellular traps in ex vivo lung perfusion perfusate predict the clinical outcome of lung transplant recipients.

Eur Respir J. 2019 04;53(4):

Authors: Caldarone L, Mariscal A, Sage A, Khan M, Juvet S, Martinu T, Zamel R, Cypel M, Liu M, Palaniyar N, Keshavjee S

PMID: 30655281 [PubMed - indexed for MEDLINE]

Nutrition and Markers of Disease Severity in Patients With Bronchiectasis.

Chronic Obstr Pulm Dis. 2020 Oct;7(4):390-403

Authors: Despotes KA, Choate R, Addrizzo-Harris D, Aksamit TR, Barker A, Basavaraj A, Daley CL, Eden E, DiMango A, Fennelly K, Philley J, Johnson MM, McShane PJ, Metersky ML, O'Donnell AE, Olivier KN, Salathe MA, Schmid A, Thomashow B, Tino G, Winthrop KL, Knowles MR, Daniels MLA, Noone PG

Abstract
Background: Increasing numbers of patients are being diagnosed with bronchiectasis, yet much remains to be elucidated about this heterogeneous patient population. We sought to determine the relationship between nutrition and health outcomes in non-cystic fibrosis (non-CF) bronchiectasis, using data from the U.S. Bronchiectasis Nontuberculous Mycobacterial Research Registry (U.S. BRR).
Methods: This was a retrospective, observational, longitudinal study using 5-year follow-up data from the BRR. Bronchiectasis was confirmed on computed tomography (CT). We stratified patients into nutrition categories using body mass index (BMI), and correlated BMI to markers of disease severity.
Results: Overall, n = 496 patients (mean age 64.6- ± 13 years; 83.3% female) were included. At baseline 12.3% (n = 61) were underweight (BMI < 18.5kg/m2), 63.9% (n = 317) had normal weight (BMI ≥ 18.5kg/m2 and <25.0kg/m2), 17.3% (n = 86) were overweight (BMI ≥ 25.0kg/m2 and < 30.0kg/m2), and 6.5% (n= 32) were obese (BMI ≥ 30kg/m2). Men were overrepresented in the overweight and obese groups (25.6% and 43.8% respectively, p < 0.0001). Underweight patients had lower lung function (forced expiratory volume in 1 second [FEV1] % predicted) than the other weight groups (64.5 ± 22, versus 73.5 ± 21, 68.5 ± 20, and 76.5 ± 21 in normal, overweight, and obese groups respectively, p = 0.02). No significant differences were noted between BMI groups for other markers of disease severity at baseline, including exacerbation frequency or hospitalization rates. No significant differences were noted in BMI distribution between patients with and without Pseudomonas, non-tuberculous mycobacteria, or by cause of bronchiectasis. The majority of patients demonstrated stable BMI over 5 years.
Conclusions: Although underweight patients with bronchiectasis have lower lung function, lower BMI does not appear to relate to other markers of disease severity in this patient population.

PMID: 33108111 [PubMed - as supplied by publisher]

Epidemiology, diagnosis & treatment of non-tuberculous mycobacterial diseases.

Indian J Med Res. 2020 Sep;152(3):185-226

Authors: Sharma SK, Upadhyay V

Abstract
Non-tuberculous mycobacteria (NTM) are ubiquitously present in the environment, but NTM diseases occur infrequently. NTM are generally considered to be less virulent than Mycobacterium tuberculosis, however, these organisms can cause diseases in both immunocompromised and immunocompetent hosts. As compared to tuberculosis, person-to-person transmission does not occur except with M. abscessus NTM species among cystic fibrosis patients. Lung is the most commonly involved organ, and the NTM-pulmonary disease (NTM-PD) occurs frequently in patients with pre-existing lung disease. NTM may also present as localized disease involving extrapulmonary sites such as lymph nodes, skin and soft tissues and rarely bones. Disseminated NTM disease is rare and occurs in individuals with congenital or acquired immune defects such as HIV/AIDS. Rapid molecular tests are now available for confirmation of NTM diagnosis at species and subspecies level. Drug susceptibility testing (DST) is not routinely done except in non-responsive disease due to slowly growing mycobacteria ( M. avium complex, M. kansasii) or infection due to rapidly growing mycobacteria, especially M. abscessus. While the decision to treat the patients with NTM-PD is made carefully, the treatment is given for 12 months after sputum culture conversion. Additional measures include pulmonary rehabilitation and correction of malnutrition. Treatment response in NTM-PD is variable and depends on isolated NTM species and severity of the underlying PD. Surgery is reserved for patients with localized disease with good pulmonary functions. Future research should focus on the development and validation of non-culture-based rapid diagnostic tests for early diagnosis and discovery of newer drugs with greater efficacy and lesser toxicity than the available ones.

PMID: 33107481 [PubMed - in process]

Sickle cell trait newborn screen results: disclosure and management.

J Community Genet. 2020 Oct 26;:

Authors: Lilley M, Hoang S, Blumenschein P, Peturson AM, Sosova I, Macneil L, Ridsdale R, Christian S

Abstract
This study aims to evaluate the notification process of sickle cell trait (SCT) identified by newborn screening in Alberta. On April 1, 2019, Alberta began newborn screening for sickle cell disease (SCD) and elected to report sickle cell trait (SCT). For 1 year, healthcare providers (HCPs) were sent a questionnaire which addressed the perceived importance of disclosing the SCT results, whether HCPs felt competent in disclosing the result, knowledge of available resources, and comfort with coordinating and interpreting testing for the newborn's parents. As a control, we collected data from HCPs receiving positive cystic fibrosis (CF) newborn screen results. A total of 107 out of 203 SCT questionnaires were returned and 41 of 66 CF questionnaires were returned. Respondents felt it was important that the results be shared with families (98% and 100%, respectively). Most respondents felt competent (SCT: 95%; CF: 85%), and willing to disclose the result to the family (SCT: 92%; CF: 88%). Fewer respondents were comfortable interpreting the results (SCT: 70%; CF: 51%)), and willing to arrange parental testing (SCT: 61%; CF: 59%). Family practitioners were significantly more willing to arrange SCT parental testing (88%) compared to pediatricians (40%) (OR = 5.3; CI 1.9, 15.4; p < 0.001). HCP comments revealed two themes: referral to another HCP for follow-up and identification of the primary HCP. Results support this disclosure process, and HCPs felt comfortable following up with SCT newborn screen results. The study identified challenges such as pediatricians being less comfortable ordering parental testing and the ordering HCP not always being the primary care provider.

PMID: 33106985 [PubMed - as supplied by publisher]