iScience. 2021 Dec 31;25(1):103710. doi: 10.1016/j.isci.2021.103710. eCollection 2022 Jan 21.

ABSTRACT

Characterization of I37R, a mutation located in the lasso motif of the CFTR chloride channel, was conducted by theratyping several CFTR modulators from both potentiator and corrector classes. Intestinal current measurements in rectal biopsies, forskolin-induced swelling (FIS) in intestinal organoids, and short circuit current measurements in organoid-derived monolayers from an individual with I37R/F508del CFTR genotype demonstrated that the I37R-CFTR results in a residual function defect amenable to treatment with potentiators and type III, but not type I, correctors. Molecular dynamics of I37R using an extended model of the phosphorylated, ATP-bound human CFTR identified an altered lasso motif conformation which results in an unfavorable strengthening of the interactions between the lasso motif, the regulatory (R) domain, and the transmembrane domain 2 (TMD2). Structural and functional characterization of the I37R-CFTR mutation increases understanding of CFTR channel regulation and provides a potential pathway to expand drug access to CF patients with ultra-rare genotypes.

PMID:35072004 | PMC:PMC8761696 | DOI:10.1016/j.isci.2021.103710

Pediatr Qual Saf. 2022 Jan 21;7(1):e529. doi: 10.1097/pq9.0000000000000529. eCollection 2022 Jan-Feb.

ABSTRACT

INTRODUCTION: Timely data entry into patient registries is foundational to learning health systems such as the Cystic Fibrosis Learning Network. The US Cystic Fibrosis Foundation Patient Registry (CFFPR) is an established registry that collects encounter data for clinical and research activities. Coordinators manually enter approximately 1,500 encounters annually at our institution, but there is limited evidence for interventions facilitating timely data entry. Our institution aimed to reduce the number of days between a clinical encounter and data entry into the CFFPR from an average of 43 days (range 0 to 183 days) to less than 30 days in a 3-month interval.

METHODS: Data coordinators tested interventions to address barriers in four themes: accountability, work burden, communication, and visibility using plan-do-study-act cycles. We used statistical process control charts to assess progress on average time of entry. Coordinators provided feedback about acceptability and satisfaction for process changes.

RESULTS: Initial interventions standardized process and reduced average time to data entry from 42.6 to 22.5 days in 3 months, but this process was not stable in the subsequent 6 months. Subsequent changes to increase metric visibility and improve team communication increased stability and decreased the average time to data entry to 23.0 days. Coordinators reported high satisfaction with process changes and have sustained improved time for over 2 years.

CONCLUSIONS: This quality improvement project reduced and maintained data entry time by addressing significant barriers without additional personnel. Increased access to near real-time data in CFFPR accelerates learning for clinical care, quality improvement, and research.

PMID:35071963 | PMC:PMC8782120 | DOI:10.1097/pq9.0000000000000529

Front Mol Biosci. 2022 Jan 4;8:718222. doi: 10.3389/fmolb.2021.718222. eCollection 2021.

ABSTRACT

Oral microecosystem is a very complicated ecosystem that is located in the mouth and comprises oral microbiome, diverse anatomic structures of oral cavity, saliva and interactions between oral microbiota and between oral microbiota and the host. More and more evidence from studies of epidemiology, microbiology and molecular biology is establishing a significant link between oral microecosystem and respiratory diseases. Microbiota settling down in oral microecosystem is known as the main source of lung microbiome and has been associated with the occurrence and development of respiratory diseases like pneumonia, chronic obstructive pulmonary disease, lung cancer, cystic fibrosis lung disease and asthma. In fact, it is not only indigenous oral microbes promote or directly cause respiratory infection and inflammation when inhaled into the lower respiratory tract, but also internal environment of oral microecosystem serves as a reservoir for opportunistic respiratory pathogens. Moreover, poor oral health and oral diseases caused by oral microecological dysbiosis (especially periodontal disease) are related with risk of multiple respiratory diseases. Here, we review the research status on the respiratory diseases related with oral microecosystem. Potential mechanisms on how respiratory pathogens colonize oral microecosystem and the role of indigenous oral microbes in pathogenesis of respiratory diseases are also summarized and analyzed. Given the importance of oral plaque control and oral health interventions in controlling or preventing respiratory infection and diseases, we also summarize the oral health management measures and attentions, not only for populations susceptible to respiratory infection like the elderly and hospitalized patients, but also for dentist or oral hygienists who undertake oral health care. In conclusion, the relationship between respiratory diseases and oral microecosystem has been established and supported by growing body of literature. However, etiological evidence on the role of oral microecosystem in the development of respiratory diseases is still insufficient. Further detailed studies focusing on specific mechanisms on how oral microecosystem participate in the pathogenesis of respiratory diseases could be helpful to prevent and treat respiratory diseases.

PMID:35071321 | PMC:PMC8767498 | DOI:10.3389/fmolb.2021.718222

Front Cell Infect Microbiol. 2022 Jan 6;11:824042. doi: 10.3389/fcimb.2021.824042. eCollection 2021.

ABSTRACT

Cystic fibrosis (CF) is an autosomal recessive genetic disorder that is characterized by recurrent and chronic infections of the lung predominantly by the opportunistic pathogens, Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa. While S. aureus is the main colonizing bacteria of the CF lungs during infancy and early childhood, its incidence declines thereafter and infections by P. aeruginosa become more prominent with increasing age. The competitive and cooperative interactions exhibited by these two pathogens influence their survival, antibiotic susceptibility, persistence and, consequently the disease progression. For instance, P. aeruginosa secretes small respiratory inhibitors like hydrogen cyanide, pyocyanin and quinoline N-oxides that block the electron transport pathway and suppress the growth of S. aureus. However, S. aureus survives this respiratory attack by adapting to respiration-defective small colony variant (SCV) phenotype. SCVs cause persistent and recurrent infections and are also resistant to antibiotics, especially aminoglycosides, antifolate antibiotics, and to host antimicrobial peptides such as LL-37, human β-defensin (HBD) 2 and HBD3; and lactoferricin B. The interaction between P. aeruginosa and S. aureus is multifaceted. In mucoid P. aeruginosa strains, siderophores and rhamnolipids are downregulated thus enhancing the survival of S. aureus. Conversely, protein A from S. aureus inhibits P. aeruginosa biofilm formation while protecting both P. aeruginosa and S. aureus from phagocytosis by neutrophils. This review attempts to summarize the current understanding of the molecular mechanisms that drive the competitive and cooperative interactions between S. aureus and P. aeruginosa in the CF lungs that could influence the disease outcome.

PMID:35071057 | PMC:PMC8770549 | DOI:10.3389/fcimb.2021.824042

ACS Appl Bio Mater. 2022 Jan 22. doi: 10.1021/acsabm.1c01198. Online ahead of print.

ABSTRACT

Chronic lung infection with bacterial biofilms is one of the leading causes of death in cystic fibrosis (CF) patients. Among many species infecting the lung airways, Pseudomonas aeruginosa is the major pathogen colonizing and persisting throughout the patient's life. The microorganism undergoes pathoadaptation, while switching from a nonmucoid to a mucoid phenotype, improving the mechanical properties of the resulting biofilms. Previous investigation of the dynamic rheological properties of nonmucoid (PANT) and mucoid (PASL) clinical P. aeruginosa isolates exposed to interfacial stresses demonstrated that the mucoid strains formed films with stronger resistance to bending and nonlinear relaxation to compression and tension. We hypothesize that the mucoid switch provides a growth advantage to P. aeruginosa through the development of interfacial films with viscoelastic properties enabling cell survival. Here, we investigate the physiological response of the mucoid and the nonmucoid P. aeruginosa to interfacial entrapment. Our results, both macroscopic and molecular, reveal that mucoid coating plays an important role in protecting the bacteria from interfacial stresses. Cell characterizations using electron and fluorescence microscopies showed higher proportion of dead nonmucoid cells compared to mucoid cells on interfacial exposure. For example, scanning transmission electron microscopy (STEM) imaging showed that 96.6% of nonmucoid cells vs only 22.2% of mucoid cells were lysed owing to interfacial stress. Furthermore, the transcriptional profiling of P. aeruginosa cells indicated the upregulation of pel, psl, and alginate genes encoding for exopolysaccharide biomaterials is associated with mucoid cells' ability to cope with the interfacial environments. Further characterization of real-time gene regulation at interfaces will elucidate the effects of interfacial environment on the regulation of bacterial virulence.

PMID:35068143 | DOI:10.1021/acsabm.1c01198

J Clin Rheumatol. 2022 Jan 21. doi: 10.1097/RHU.0000000000001830. Online ahead of print.

ABSTRACT

Digital clubbing and hypertrophic osteoarthropathy (HOA) are long-standing clinical entities, but their prevalence have not been synthesized. We aimed to estimate the prevalence of digital clubbing and HOA in people with existing medical conditions.We comprehensively searched PubMed, Embase, and Web of Science to select studies addressing HOA or digital clubbing and published through March 23, 2021. Summary estimates of the prevalence were derived through random-effects meta-analysis and narrative synthesis. The review protocol has been registered with PROSPERO, CRD42021243934.Of 3973 records, we included 142 studies. In adults, the pooled prevalence of digital clubbing was 33.4% (95% confidence interval [CI], 16.6-52.8), 31.3% (95% CI, 22.4-41.1), 27% (95% CI, 9.4-49.5), and 22.8% (95% CI, 10.8-37.6) in subjects with intestinal diseases, interstitial lung diseases, infective endocarditis, and hepatic diseases, respectively. In children and adolescents, the pooled prevalence of digital clubbing was 29.1% (95% CI, 19.4-39.9), 23% (95% CI, 9.0-41.1), 19.5% (95% CI, 4.1-42.4), and 17.1% (95% CI, 9.5-26.5) in subjects with human immunodeficiency virus infection, hemoglobinopathies, cystic fibrosis, and tuberculosis. The pooled prevalence of HOA was 10.1% (95% CI, 2.0-23.1) in adults with cancers, and 5% (95% CI, 2.5-8.2) in children and adolescents with cystic fibrosis.In conclusion, the prevalence of digital clubbing varied across disease groups in both adults and children. Full-spectrum HOA was mostly reported in adults with liver disease and cancers, and in children and adolescents with cystic fibrosis.

PMID:35067513 | DOI:10.1097/RHU.0000000000001830

J Biol Chem. 2022 Jan 20:101615. doi: 10.1016/j.jbc.2022.101615. Online ahead of print.

ABSTRACT

Deletion of phenylalanine 508 (F508del) in the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel is the most common cause of cystic fibrosis (CF). The F508 residue is located on nucleotide-binding domain 1 (NBD1) in contact with the cytosolic extensions of the transmembrane helices, in particular intracellular loop 4 (ICL4). To investigate how absence of F508 at this interface impacts the CFTR protein, we carried out a mutagenesis scan of ICL4 by introducing second-site mutations at eleven positions in cis with F508del. Using an image-based fluorescence assay, we measured how each mutation affected membrane proximity and ion-channel function. The scan strongly validated the effectiveness of R1070W at rescuing F508del defects. Molecular dynamics simulations highlighted two features characterizing the ICL4/NBD1 interface of F508del/R1070W-CFTR: flexibility, with frequent transient formation of interdomain hydrogen bonds, and loosely stacked aromatic sidechains (F1068, R1070W, and F1074, mimicking F1068, F508 and F1074 in wild-type CFTR). F508del-CFTR displayed a distorted aromatic stack, with F1068 displaced towards the space vacated by F508, while, in F508del/R1070F-CFTR, which largely retained F508del defects, R1070F could not form hydrogen bonds and the interface was less flexible. Other ICL4 second-site mutations which partially rescued F508del-CFTR included F1068M and F1074M. Methionine side chains allow hydrophobic interactions without the steric rigidity of aromatic rings, possibly conferring flexibility to accommodate the absence of F508 and retain a dynamic interface. These studies highlight how both hydrophobic interactions and conformational flexibility might be important at the ICL4/NBD1 interface, suggesting possible structural underpinnings of F508del-induced dysfunction.

PMID:35065958 | DOI:10.1016/j.jbc.2022.101615

Am J Hum Genet. 2022 Jan 19:S0002-9297(21)00467-5. doi: 10.1016/j.ajhg.2021.12.012. Online ahead of print.

ABSTRACT

Mucus obstruction is a central feature in the cystic fibrosis (CF) airways. A genome-wide association study (GWAS) of lung disease by the CF Gene Modifier Consortium (CFGMC) identified a significant locus containing two mucin genes, MUC20 and MUC4. Expression quantitative trait locus (eQTL) analysis using human nasal epithelia (HNE) from 94 CF-affected Canadians in the CFGMC demonstrated MUC4 eQTLs that mirrored the lung association pattern in the region, suggesting that MUC4 expression may mediate CF lung disease. Complications arose, however, with colocalization testing using existing methods: the locus is complex and the associated SNPs span a 0.2 Mb region with high linkage disequilibrium (LD) and evidence of allelic heterogeneity. We previously developed the Simple Sum (SS), a powerful colocalization test in regions with allelic heterogeneity, but SS assumed eQTLs to be present to achieve type I error control. Here we propose a two-stage SS (SS2) colocalization test that avoids a priori eQTL assumptions, accounts for multiple hypothesis testing and the composite null hypothesis, and enables meta-analysis. We compare SS2 to published approaches through simulation and demonstrate type I error control for all settings with the greatest power in the presence of high LD and allelic heterogeneity. Applying SS2 to the MUC20/MUC4 CF lung disease locus with eQTLs from CF HNE revealed significant colocalization with MUC4 (p = 1.31 × 10-5) rather than with MUC20. The SS2 is a powerful method to inform the responsible gene(s) at a locus and guide future functional studies. SS2 has been implemented in the application LocusFocus.

PMID:35065708 | DOI:10.1016/j.ajhg.2021.12.012

Infect Dis Now. 2022 Jan 19:S2666-9919(22)00002-1. doi: 10.1016/j.idnow.2022.01.002. Online ahead of print.

ABSTRACT

BACKGROUND: There have been reports of COVID-19 reinfections, but the immunological characterization of these cases is partial. We report a case of reinfection with SARS-CoV-2, where the first infection occurred in the course of late pregnancy.

CASE PRESENTATION: On May 27, 2020, a 37-year-old woman gave birth at full term, 3 hours after full dilatation. She developed fever (38.3°C) after delivery. Mild biological anomalies compatible with COVID-19 were observed: lymphopenia, thrombocytopenia, elevated D-Dimers, CRP, and LDH. At 6-month follow-up, she reported having contracted COVID-19 with high fever, rhinorrhea, hand frostbites, cough, headache, dysgeusia, and anosmia.

CONCLUSIONS: We report a case of COVID-19 reinfection with a first mild infection during late pregnancy and a more aggressive second infection 5 months later.

PMID:35065269 | DOI:10.1016/j.idnow.2022.01.002

J Cyst Fibros. 2022 Jan 18:S1569-1993(22)00026-1. doi: 10.1016/j.jcf.2022.01.005. Online ahead of print.

ABSTRACT

Aquagenic wrinkling of palms (AWP) in cystic fibrosis (CF) patients and common CFTR mutations is recognized as a frequent symptom of the disease. The long-term effect of CFTR targeting therapy on AWP has not been studied. AWP was monitored in 16 CF patients (8 children and 8 adults) before and for 6 months after initiation of ivacaftor therapy. Thirteen (81.3%) patients had at least mild and 8/16 (50%) moderate-to-severe AWP at baseline. AWP improved with ivacaftor therapy. This observation suggests that AWP is also common in individuals with CF and relatively rare mutations and is directly related to CFTR function.

PMID:35063397 | DOI:10.1016/j.jcf.2022.01.005

J Cyst Fibros. 2022 Jan 19:S1569-1993(22)00025-X. doi: 10.1016/j.jcf.2022.01.004. Online ahead of print.

ABSTRACT

More than five decades after the introduction of the quantitative pilocarpine iontophoresis technique, surveys still highlight inconsistencies in the performance and reporting of sweat tests in Europe. The sweat test remains key for the Cystic Fibrosis (CF) diagnostic pathway for all age groups, as it reflects the basic pathophysiological defect in the sweat gland. It is also critical following newborn screening as a confirmatory diagnostic step. Despite its importance, sweat test quality is variable whether performed in the laboratory or as a point of care test. The ECFS DNWG aims to improve sweat test performance, taking into account the barriers and issues identified in the European survey; the previous step in the ECFS sweat test project. This manuscript proposes a grading of sweat test guidance from "acceptable" to "optimal", aiming to pragmatically improve quality while taking into account local situations, especially in resource-limited settings.

PMID:35063396 | DOI:10.1016/j.jcf.2022.01.004

Lancet Respir Med. 2022 Jan 18:S2213-2600(22)00017-0. doi: 10.1016/S2213-2600(22)00017-0. Online ahead of print.

NO ABSTRACT

PMID:35063078 | DOI:10.1016/S2213-2600(22)00017-0

BMC Pulm Med. 2022 Jan 21;22(1):42. doi: 10.1186/s12890-022-01825-2.

ABSTRACT

BACKGROUND: CFTR-modulators are a category of drugs that facilitate trafficking and opening of the abnormal CFTR protein in individuals with cystic fibrosis (CF) who have certain genetic mutations. Clinical trial data show that individuals taking CFTR-modulators have increased or stable lung function (FEV1) as well as reduced frequency of pulmonary exacerbations. There are no data on whether CFTR-modulators influence psychosocial aspects of the lives of individuals with CF. The purpose of this qualitative study was to explore how the introduction of CFTR-modulators has affected individuals' lived experiences outside of clinical health variables; that is, to explore whether there is a relationship between using CFTR-modulator drugs and the psychological and social aspects of the lives of individuals with CF, including: career, relationships, family planning and psychological functioning.

METHODS: Eight men and women with CF ages 24-32, with a history of taking any approved CFTR-modulator for at least six months, were recruited from an adult CF center. A semi-structured interview guide was used to interview the participants. The data were coded using a grounded theory approach with an iterative methodology.

RESULTS: Four themes emerged from the data: stability, identity, potentiality, and hope.

CONCLUSIONS: Although these themes cannot be generalized to all individuals with CF, this study provides preliminary data for how CFTR-modulators may influence an individual with CF's outlook on life and that these individuals are feeling hopeful about the future.

PMID:35062937 | DOI:10.1186/s12890-022-01825-2

Eur J Public Health. 2022 Jan 21:ckab194. doi: 10.1093/eurpub/ckab194. Online ahead of print.

ABSTRACT

BACKGROUND: The proportion of reported causes of death (CoDs) that are not underlying causes can be relevant even in high-income countries and seriously affect health planning. The Global Burden of Disease (GBD) study identifies these 'garbage codes' (GCs) and redistributes them to underlying causes using evidence-based algorithms. Planners relying on vital registration data will find discrepancies with GBD estimates. We analyse these discrepancies, through the analysis of GCs and their redistribution.

METHODS: We explored the case of Italy, at national and regional level, and compared it to nine other Western European countries with similar population sizes. We analysed differences between official data and GBD 2019 estimates, for the period 1990-2017 for which we had vital registration data for most select countries.

RESULTS: In Italy, in 2017, 33 000 deaths were attributed to unspecified type of stroke and 15 000 to unspecified type of diabetes, these making a fourth of the overall garbage. Significant heterogeneity exists on the overall proportion of GCs, type (unspecified or impossible underlying causes), and size of specific GCs among regions in Italy, and among the select countries. We found no pattern between level of garbage and relevance of specific GCs. Even locations performing below average show interesting lower levels for certain GCs if compared to better performing countries.

CONCLUSIONS: This systematic analysis suggests the heterogeneity in GC levels and causes, paired with a more detailed analysis of local practices, strengths and weaknesses, could be a positive element in a strategy for the reduction of GCs in Italy.

PMID:35061890 | DOI:10.1093/eurpub/ckab194

J Membr Biol. 2022 Jan 21. doi: 10.1007/s00232-021-00212-y. Online ahead of print.

ABSTRACT

Shroom is a family of related proteins linked to the actin cytoskeleton, and one of them, xShroom1, is constitutively expressed in Xenopus laevis oocytes which is required for the expression of the epithelial sodium channel (ENaC). On the other hand, ENaC and the cystic fibrosis transmembrane regulator (CFTR) are co-expressed in many types of cells with a negative or positive interaction depending on the studied tissues. Here, we measured the amiloride-sensitive ENaC currents (INaamil) and CFTR currents (ICFTR) with voltage clamp techniques in oocytes co-injected with ENaC and/or CFTR and xShroom1 antisense oligonucleotides. The objective was to study the mechanism of regulation of ENaC by CFTR when xShroom1 was suppressed and the endocytic traffic of CFTR was blocked. CFTR activation had a measurable negative effect on ENaC and this activation resulted in a greater inhibition of INaamil than with xShroom1 antisense alone. Our results with Dynasore, a drug that acts as an inhibitor of endocytic pathways, suggest that the changes in INaamil by xShroom1 downregulation were probably due to an increment in channel endocytosis. An opposite effect was observed when ICFTR was measured. Thus, when xShroom1 was downregulated, the ICFTR was larger than in the control experiments and this effect is not observed with Dynasore. A speculative explanation could be that xShroom1 exerts a dual effect on the endocytic traffic of ENaC and CFTR and these actions were canceled with Dynasore. In the presence of Dynasore, no difference in either INaamil or ICFTR was observed when xShroom1 was downregulated.

PMID:35061048 | DOI:10.1007/s00232-021-00212-y

J Cell Sci. 2022 Jan 21:jcs.259002. doi: 10.1242/jcs.259002. Online ahead of print.

ABSTRACT

Membrane proteins often cluster in nanoscale membrane domains (lipid rafts) that coalesce into ceramide-rich platforms during cell stress, however the clustering mechanisms remain uncertain. The cystic fibrosis transmembrane conductance regulator (CFTR), which is mutated in cystic fibrosis (CF), forms clusters that are cholesterol-dependent and become incorporated into long-lived platforms during hormonal stimulation. We report here that clustering does not involve known tethering interactions of CFTR with PDZ domain proteins, filamin A or the actin cytoskeleton. It also does not require CFTR palmitoylation but is critically dependent on membrane lipid order and is induced by detergents that increase the phase separation of membrane lipids. Clustering and integration of CFTR into ceramide-rich platforms are abolished by the disease mutations F508del and S13F and rescued by the CFTR modulators elexacaftor+tezacaftor. These results indicate CF therapeutics that correct mutant protein folding restore both trafficking and normal lipid interactions in the plasma membrane.

PMID:35060604 | DOI:10.1242/jcs.259002

Clin Respir J. 2022 Jan 21. doi: 10.1111/crj.13473. Online ahead of print.

ABSTRACT

INTRODUCTION: Individuals with cystic fibrosis (CF) may be at increased risk of pulmonary embolism (PE). Symptoms of PE overlap substantially with those of CF respiratory exacerbations. CF patients commonly undergo chest computed tomography (CT) angiograms (CTPA) to evaluate for PE, but little is known about the clinical presentation and diagnosis of PE in this population.

OBJECTIVES: The objectives of this study are to determine the diagnostic yield of CTPA for PE in adult patients with CF and assess the utility of the Revised Geneva Score (RGS) in this population.

METHODS: Retrospective review of all CTPA results was performed on CF patients with suspected PE at a large CF center from 1 January 2011 through 31 March 2017. Patient demographics, medical history, and presenting signs and symptoms were abstracted by chart review.

RESULTS: A total of 103 unique CTPA studies were performed in 68 patients. Most were hospitalized at the time of CTPA, predominantly for respiratory manifestations of CF. CTPA identified four patients with PE. The small number of positive studies precluded analysis of predictors of PE. Fewer PE were diagnosed than predicted by the Revised Geneva Score, which was intermediate probability in 77/103 (75%) patients.

CONCLUSION: The prevalence of PE in CF patients undergoing CTPA for suspected PE was 4%, which is lower than predicted by the Revised Geneva Score. This may be due to a large overlap in the signs and symptoms of PE and exacerbations of CF lung disease.

PMID:35060348 | DOI:10.1111/crj.13473

J Clin Transl Endocrinol. 2021 Dec 21;27:100291. doi: 10.1016/j.jcte.2021.100291. eCollection 2022 Mar.

ABSTRACT

The advent of highly effective CFTR modulator therapies has slowed the progression of pulmonary complications in people with cystic fibrosis. There is increased interest in cystic fibrosis bone disease (CFBD) due to the increasing longevity of people with cystic fibrosis. CFBD is a complex and multifactorial disease. CFBD is a result of hypomineralized bone leading to poor strength, structure and quality leading to susceptibility to fractures. The development of CFBD spans different age groups. The management must be tailored to each group with nuance and based on available guidelines while balancing therapeutic benefits to risks of long-term use of bone-active medication. For now, the mainstay of treatment includes bisphosphonates. However, the long-term effects of bisphosphonate treatment in people with CF are not fully understood. We describe newer agents available for osteoporosis treatment. Still, the lack of data behooves trials of monoclonal antibodies treatments such as Denosumab and Romozosumab and anabolic bone therapy such as teriparatide and Abaloparatide. In this review, we also summarize screening and non-pharmacologic treatment of CFBD and describe the various options available for the pharmacotherapy of CFBD. We address the prospect of CFTR modulators on bone health while awaiting long-term trials to describe the effects of these medications on bone health.

PMID:35059303 | PMC:PMC8760456 | DOI:10.1016/j.jcte.2021.100291

Respir Med Case Rep. 2022 Jan 1;36:101572. doi: 10.1016/j.rmcr.2021.101572. eCollection 2022.

ABSTRACT

In Michigan (MI), NBS for CF was started in October 2007 using the IRT/DNA protocol. In 2016, a component of the Hologic molecular test kit used by the MI NBS lab was recalled (40 CF mutation 2nd tier test). This recall had a major impact on states using the Hologic test kits in their NBS programs. Michigan specimens were sent to another state's NBS Lab for 2nd tier testing using the Luminex 60 mutation test kit until the Luminex kit could be procured and validated in MI. In this report, we present five cases born during this time period. These cases were initially reported out as having normal NBS results for CF but had heterozygous F508 del (c.1521_1523delCTT) mutations later identified. Of the five cases, one was diagnosed with CF (Case1), one with CF related metabolic syndrome (CRMS), and the other three were carriers.

PMID:35059286 | PMC:PMC8760430 | DOI:10.1016/j.rmcr.2021.101572

Arch Dis Child. 2022 Feb;107(2):134-140. doi: 10.1136/archdischild-2021-321795. Epub 2021 Jun 21.

ABSTRACT

OBJECTIVE: To explore parent perspectives on accessing mental healthcare for children with a chronic physical health condition.

DESIGN: Qualitative research using semistructured interviews and Framework Analysis. Rankings were used to select attributes for a Discrete Choice Experiment (DCE).

SETTING: Four specialty outpatient clinics (diabetes, epilepsy, bronchiectasis unrelated to cystic fibrosis and epidermolysis bullosa) at an Australian tertiary paediatric hospital.

PARTICIPANTS: Eighteen parents of children with a chronical physical health condition.

RESULTS: Most parents identified the child's general practitioner and/or hospital team as an initial pathway to seek help if they were worried about their child's mental health. Parents see mental healthcare as part of care for the whole child and want the outpatient clinics to proactively discuss child and family mental health, as well as refer to appropriate services as needed. The hospital being a familiar, child-friendly environment was identified as a key reason the hospital might be a desired place to access mental healthcare, as previous research has found. Six attributes of mental health services were identified as important and will be included in an upcoming DCE: travel time, cost, wait time, available hours, knowledge of physical health condition, and recommendation.

CONCLUSIONS: This study highlights the opportunity presented in specialist outpatient clinics to address the often unmet mental healthcare needs of children with chronic physical health conditions. Parents identified practical ways for outpatient clinics to better facilitate access to mental healthcare. These will be further explored through a quantitative study of parent preferences.

PMID:35058237 | DOI:10.1136/archdischild-2021-321795