HRB Open Res. 2021 Feb 9;4:17. doi: 10.12688/hrbopenres.13215.1. eCollection 2021.

ABSTRACT

Background: This study aims to examine the potential of currently available administrative health data for palliative and end-of-life care (PEoLC) research in Ireland. Objectives include to i) identify administrative health data sources for PEoLC research ii) describe the challenges and opportunities of using these and iii) estimate the impact of recent health system reforms and changes to data protection laws. Methods: The 2017 Health Information and Quality Authority catalogue of health and social care datasets was cross-referenced with a recognised list of diseases with associated palliative care needs. Criteria to assess the datasets included population coverage, data collected, data dictionary and data model availability and mechanisms for data access. Results: Eight datasets with potential for PEoLC research were identified, including four disease registries, (cancer, cystic fibrosis, motor neurone and interstitial lung disease), death certificate data, hospital episode data, community prescription data and one national survey. The ad hoc development of the health system in Ireland has resulted in i) a fragmented information infrastructure resulting in gaps in data collections particularly in the primary and community care sector where much palliative care is delivered, ii) ill-defined data governance arrangements across service providers, many of whom are not part of the publically funded health service and iii) systemic and temporal issues that affect data quality. Initiatives to improve data collections include introduction of i) patient unique identifiers, ii) health entity identifiers and iii) integration of the eircode postcodes. Recently enacted general data protection and health research regulations will clarify legal and ethical requirements for data use. Conclusions: With appropriate permissions, detailed knowledge of the datasets and good study design currently available administrative health data can be used for PEoLC research. Ongoing reform initiatives and recent changes to data privacy laws will facilitate future use of administrative health data for PEoLC research.

PMID:33842831 | PMC:PMC8014706 | DOI:10.12688/hrbopenres.13215.1

J Infect Prev. 2021 Jan;22(1):39-41. doi: 10.1177/1757177420948593. Epub 2020 Aug 29.

ABSTRACT

Conventional microbiological investigations, including pathogen detection, antibiotic susceptibility testing and molecular epidemiological testing, are valuable tools in helping to manage nosocomial outbreaks. However, the microbiology laboratory, by using other techniques, can investigate additional microbiological aspects of outbreaks, which are often overlooked. Bacterial isolates (n=6) from an outbreak of Pseudomonas aeruginosa bacteraemia in a neonatal intensive care unit (NICU) in Belfast were examined. Enhanced microbiology testing included: (1) susceptibility of outbreak strains to biocides in common use in the unit; (2) effect of organic soils relevant to the area of the outbreak and their effect on the efficacy of biocide; and (3) the persistence of outbreak strains in organic soils. By emulating bespoke conditions of the outbreak, these methods were able to demonstrate that: (1) biocides were effective against the outbreak strains; (2) the critical concentration of soil which rendered biocide ineffective; and (3) how long the outbreak strains could persist. Enhanced microbiological analysis outside the conventional repertoire of testing may therefore offer valuable data that may help guide outbreak management teams.

PMID:33841560 | PMC:PMC7841714 | DOI:10.1177/1757177420948593

J Heart Lung Transplant. 2021 Feb 27:S1053-2498(21)02203-8. doi: 10.1016/j.healun.2021.02.017. Online ahead of print.

ABSTRACT

BACKGROUND: Lung transplantation (LTx) requires a calcineurin inhibitor-based immunosuppressive regimen. A once daily (QD) tacrolimus regimen was developed to increase medication adherence. However, data concerning its safety and efficacy in LTx are lacking.

METHODS: In this prospective study, stable LTx patients were consecutively converted from twice daily (BID) tacrolimus to QD tacrolimus on a 1 mg:1 mg basis. Trough level (Cmin), renal function, cholesterol, fasting glucose, potassium and lung function were monitored six months before and up to one year after conversion. Adherence and its barriers were assessed by self-reported questionnaires (Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS) and Identification of Medication Adherence Barriers questionnaire (IMAB)) and blood-based assays (mean Cmin and coefficient of variation (CV)).

RESULTS: We included 372 patients, in whom we observed a decrease in tacrolimus Cmin of 18.5% (p < 0.0001) post-conversion, requiring subsequent daily dose adaptations in both cystic fibrosis (CF) (n = 72) and non-CF patients (n = 300). We observed a small decrease in eGFR one year post-conversion (p = 0.024). No significant changes in blood creatinine, potassium, fasting glucose, cholesterol or rate of lung function decline were observed. In a subgroup of 166 patients, significantly fewer patients missed doses (8.4% vs. 19.3%, p = 0.016) or had irregular intake post-conversion (19.3% vs. 32.5%, p = 0.019). Mean Cmin and CV, as well as the total number of barriers, also decreased significantly post-conversion.

CONCLUSIONS: In LTx, conversion from BID to QD tacrolimus (1 mg:1 mg) requires close monitoring of tacrolimus Cmin. QD tacrolimus after transplantation is safe with respect to renal function, metabolic parameters and allograft function and improves LTx recipient adherence.

PMID:33840608 | DOI:10.1016/j.healun.2021.02.017

Am J Transplant. 2021 Apr 11. doi: 10.1111/ajt.16602. Online ahead of print.

ABSTRACT

Vaccine-preventable viral infections are associated with increased risk of morbidity and mortality in post-transplant patients on immunosuppression regimens. Therefore, we studied rates of immunity against vaccine-preventable viruses in lung transplantation (LTx) candidates and their associations with underlying lung disease and clinical characteristics. We retrospectively studied 1025 consecutive adult patients who underwent first-time evaluation for LTx at a single center between January 2016 and October 2018. Viruses studied included varicella zoster (VZV), measles, and mumps. Young age (17-48 yo) was negatively associated with immunity for VZV (OR 4.54, p<0.001), measles (OR 15.45, p <0.001) and mumps (OR 3.1, p <0.001), as compared to those 65+. Many LTx candidates with cystic fibrosis (CF) had undetectable virus-specific antibody titers including:13.5% for VZV, 19.1% for measles, and 15.7% for mumps with significant odds of undetectable titers for VZV (OR 4.54, p<0.001) and measles (OR 2.32, p=0.010) as compared to those without CF. Therefore, a substantial number of patients undergoing LTx evaluation had undetectable virus-specific antibody titers. Our results emphasize the importance of screening for immunity to vaccine-preventable infections in this population and the need for revaccination in selected patients to boost their humoral immunity prior to transplantation.

PMID:33840158 | DOI:10.1111/ajt.16602

J Biol Chem. 2021 Mar 4;296:100392. doi: 10.1016/j.jbc.2021.100392. Online ahead of print.

ABSTRACT

Bacterial biofilms are surface-associated multicellular communities that are highly resistant to removal. Scheffler et al. discovered that Pseudomonas aeruginosa secretes a small molecule that inhibits other P. aeruginosa cells from adsorbing to surfaces by interfering with type IV pili dynamics. The inhibition of cell adsorption could present a method to prevent biofilm formation on sensitive surfaces in hospitals and industry.

PMID:33839681 | DOI:10.1016/j.jbc.2021.100392

J Biol Chem. 2021 Apr 8:100650. doi: 10.1016/j.jbc.2021.100650. Online ahead of print.

ABSTRACT

Most patients with cystic fibrosis (CF) suffer from acute and chronic pulmonary infections with bacterial pathogens, which often determine their life quality and expectancy. Previous studies have demonstrated a down-regulation of the acid ceramidase in CF epithelial cells resulting in an increase of ceramide and a decrease of sphingosine. Sphingosine kills many bacterial pathogens and the down-regulation of sphingosine seems to determine the infection susceptibility of cystic fibrosis mice and patients. It is presently unknown how deficiency of the cystic fibrosis transmembrane conductance regulator (CFTR) connects to a marked down-regulation of the acid ceramidase in human and murine CF epithelial cells. Here, we employed quantitative PCR, western blot analysis and enzyme activity measurements to study the role of IRF8 for acid ceramidase regulation. We report that genetic deficiency or functional inhibition of CFTR/Cftr results in an up-regulation of interferon regulatory factor 8 (IRF8) and a concomitant down-regulation of acid ceramidase expression with CF and an increase of ceramide and a reduction of sphingosine levels in tracheal and bronchial epithelial cells from both human individuals or mice. CRISPR/Cas9- or siRNA-mediated down-regulation of IRF8 prevented changes of acid ceramidase, ceramide and sphingosine in CF epithelial cells and restored resistance to Pseudomonas aeruginosa infections, which is one of the most important and common pathogens in lung infection of patients with CF. These studies indicate that CFTR-deficiency causes a down-regulation of acid ceramidase via up-regulation of IRF8, which is a central pathway to control infection susceptibility of CF cells.

PMID:33839155 | DOI:10.1016/j.jbc.2021.100650

Eur J Radiol. 2021 Mar 31;139:109653. doi: 10.1016/j.ejrad.2021.109653. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to assess the feasibility of Self-gated Non-Contrast-Enhanced Functional Lung (SENCEFUL) MRI for detection of pulmonary perfusion deficits in patients with cystic fibrosis.

METHODS: Twenty patients with cystic fibrosis and 20 matched healthy controls underwent SENCEFUL-MRI at 1.5 T with reconstruction of perfusion and perfusion phase maps (i.e. comparable to pulse wave delays). Four blinded readers rated both types of maps separately followed by simultaneous assessment thereof. Perfusion phase data was plotted in histograms and a Peak-to-Offset ratio was calculated for comparison to subjective scoring and correlation (Spearman) to lung function parameters. Sensitivity, specificity and positive and negative predictive values were calculated for subjective scoring and Peak-to-Offset ratios. Intraclass correlation (ICC) was used to assess the interrater agreement.

RESULTS: Readers attributed pathological ratings 2.2-3.5 times more frequently to the CF-group. The sensitivity with regard to a correct assignment to CF was similar between ratings (perfusion only vs. perfusions phase only vs. simultaneous assessment: 0.54-0.56), while specificity increased from 0.75 to 0.85 for simultaneous assessment. ICC was 0.77-0.84 for subjective scoring. ROC-analysis of Peak-to-Offset ratios on a mean per-subject basis revealed a sensitivity of 0.75 and specificity of 0.85 (PPV 0.83, NPV 0.77). Functional pulmonary parameters indicative of bronchial obstruction and Peak-to-Offset ratios showed positive correlation (FEV1: 0.77; FEF75: 0.76).

CONCLUSIONS: SENCEFUL-MRI bears the potential for monitoring CF including disease-associated patterns of altered pulmonary perfusion. The proposed Peak-to-Offset ratio derived from pulmonary perfusion phase measurements could represent an objective future marker for perfusion impairment.

PMID:33838429 | DOI:10.1016/j.ejrad.2021.109653

J Clin Psychol Med Settings. 2021 Apr 10. doi: 10.1007/s10880-021-09774-4. Online ahead of print.

ABSTRACT

Evidence suggests that individuals with Cystic Fibrosis (CF) experience difficulties with sleep architecture and hygiene, although research is limited. There are currently no behavioral sleep interventions for youth with CF. The current study used qualitative methods to understand sleep needs and concerns among youth with CF, as well as to obtain feedback about potentially useful behavioral sleep intervention strategies. Semi-structured interviews were conducted with youth with CF between the ages of 11-17 and their parents. Themes were extracted from the data and will be used to inform the development of a brief behavioral sleep intervention for youth with CF. Youth and their parents described several CF-specific sleep concerns, often related to respiratory symptoms, and a number of strategies used to manage these concerns. They also described concerns that apply to the general population, including pervasive use of technology around bedtime. Many evidence-based behavioral sleep intervention strategies are acceptable to youth with CF, although modifications are appropriate to reduce time burden and address CF-specific needs. Youth with CF experience a number of disease-specific and more generalized sleep concerns which are likely amenable to behavioral intervention. Results from this study will be used to inform the development of a brief behavioral sleep intervention for youth with CF.

PMID:33837923 | DOI:10.1007/s10880-021-09774-4

Ital J Pediatr. 2021 Apr 9;47(1):87. doi: 10.1186/s13052-021-01040-5.

ABSTRACT

BACKGROUND: Cystic Fibrosis newborn screening (CFNBS) is the optimal method to diagnose the disease during the asymptomatic period. The aim of the study was to determine how CFNBS affects long term clinical outcomes.

METHODS: Data from infants who were born in Lodz Voivodship, referred to CF center as a part of CFNBS according to IRT/DNA protocol were compared to the data of children with established CF diagnosis before the start of NBS in Poland (Group CF, n = 52).

RESULTS: In 37 children (during 151 referred infants) the diagnosis of CF was established due to CF NBS (CF NBS Group, n = 37). The average time of diagnosis was 1.59 month in Group CF NBS and 45.25 months in 52 children from Group CF. Pulmonary exacerbations occurred on average 4.2 times in Group CFNBS and they were hospitalized on average 0.5 times compared to Group CF - respectively 6.77 and 2.14 (p < 0.001). The number of PA infected patients increased between the fifth and eighth year of age (OR = 1.16 (95% CI: 1.04-19) (P = 0.007)) regardless of the study group (P = 0.984). Patients with MRSA infection have a higher risk of PA infections in subsequent years of their life (OR = 1.45 (95% CI: 1.03-2.03) (P = 0.032)).

CONCLUSIONS: CF NBS has beneficial effects primarily on decrease of pulmonary withhope for a longer life expectancy and better and centralised treatment in multidisciplinary CF focused centres.

PMID:33836782 | DOI:10.1186/s13052-021-01040-5

Am J Otolaryngol. 2021 Mar 31;42(5):103016. doi: 10.1016/j.amjoto.2021.103016. Online ahead of print.

ABSTRACT

PURPOSE: Pediatric cystic fibrosis (CF) patients have a variable onset, severity, and progression of sinonasal disease. The objective of this study was to identify genotypic and phenotypic factors associated with CF that are predictive of sinonasal disease, recurrent nasal polyposis, and failure to respond to standard treatment.

METHODS: A retrospective case series was conducted of 30 pediatric patients with CF chronic rhinosinusitis with and without polyps. Patient specific mutations were divided by class and categorized into high risk (Class I-III) and low risk (Class IV-V). Severity of pulmonary and pancreatic manifestations of CF, number of sinus surgeries, nasal polyposis and recurrence, age at presentation to Otolaryngology, and Pediatric Sinonasal Symptom Survey (SN-5)/Sinonasal Outcome Test (SNOT-22) scores were examined.

RESULTS: 27/30 patients (90%) had high risk mutations (Class I-III). 21/30 (70.0%) patients had nasal polyposis and 10/30 (33.3%) had recurrent nasal polyposis. Dependence on pancreatic enzymes (23/27, 85.2% vs 0/3, 0.0%, p = 0.009) and worse forced expiratory volumes (FEV1%) (mean 79, SD 15 vs mean 105, SD 12, p = 0.009) were more common in patients with high risk mutations. Insulin-dependence was more common in those with recurrent polyposis (5/10, 50% vs 2/20, 10%, p = 0.026). There was no statistical difference in ages at presentation, first polyps, or sinus surgery, or in polyposis presence, recurrence, or extent of sinus surgery based on high risk vs. low risk classification.

CONCLUSION: CF-related diabetes was associated with nasal polyposis recurrence. Patients with more severe extra-pulmonary manifestations of CF may also be at increased risk of sinonasal disease.

PMID:33836483 | DOI:10.1016/j.amjoto.2021.103016

Nutrition. 2021 Feb 27;89:111221. doi: 10.1016/j.nut.2021.111221. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study was to describe the relationship between the prevalence of Pseudomonas aeruginosa (PA) and lung function, as well as the nutritional status and type of gene mutation in adult patients with cystic fibrosis (CF).

METHODS: This cross-sectional study evaluated 103 Polish adults with CF the following: • The occurrence of PA and the level of bacterial susceptibility to antibiotics; • Type of mutation in the CFTR gene; • Nutritional status assessed by body mass index (BMI), and • Lung function measured by forced expiratory volume in 1 s (FEV1%).

RESULTS: The absence or presence of PA and the level of bacterial resistance were significantly related to the type of gene mutation (P < 0.001). In patients with a severe mutation, PA more often was extensively drug resistant or pandrug resistant compared with Pseudomonas culture-negative patients or patients with mild or unclassified mutations on both alleles. Associations were found between the presence of PA and lower values of BMI (P < 0.001), and FEV1% (P < 0.001). The risk for PA occurrence and the development of bacterial resistance increased twice in the case of severe mutation (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.62-3.89), four times when BMI decreased <18.5 (OR, 4.15; 95% CI, 1.43-10.08). and six times when FEV1% fell <40 (OR, 6.75; 95% CI, 3.11-14.64).

CONCLUSIONS: The presence of PA is associated with lower FEV1% and BMI values. Deterioration of lung function, undernutrition, and severe type of gene mutation are linked to a higher probability of PA acquisition and resistance to antibiotic treatment.

PMID:33836428 | DOI:10.1016/j.nut.2021.111221

Vet Rec. 2021 Apr;188(7):271-272. doi: 10.1002/vetr.377.

NO ABSTRACT

PMID:33835558 | DOI:10.1002/vetr.377

Immunology. 2021 Apr 9. doi: 10.1111/imm.13336. Online ahead of print.

ABSTRACT

The impairment of the cystic fibrosis transmembrane conductance regulator (CFTR) activity induces intracellular chloride (Cl- ) accumulation. The anion Cl- , acting as a second messenger, stimulates the secretion of interleukin-1β (IL-1β), which starts an autocrine positive feedback loop. Here we show that NLR family pyrin domain containing 3 (NLRP3) and caspase 1 (CASP1) are indirectly modulated by the intracellular Cl- concentration, showing maximal expression and activity at 75 mM Cl- , in the presence of the ionophores nigericin and tributyltin. The expression of PYD and CARD domain containing (PYCARD/ASC) remained constant from 0 to 125 mM Cl- . The CASP1 inhibitor VX-765 and the NLRP3 inflammasome inhibitor MCC950 completely blocked the Cl- -stimulated IL-1β mRNA expression and partially the IL-1β secretion. DCF fluorescence (cellular reactive oxygen species, cROS) and MitoSOX fluorescence (mitochondrial ROS, mtROS) also showed maximal ROS levels at 75 mM Cl- , a response strongly inhibited by the ROS scavenger N-acetyl-L-cysteine (NAC) or the NADPH oxidase (NOX) inhibitor GKT137831. These inhibitors also affected CASP1 and NLRP3 mRNA and protein expression. More importantly, the serum/glucocorticoid regulated kinase 1 (SGK1) inhibitor GSK650394, or its shRNAs, completely abrogated the IL-1β mRNA response to Cl- and the IL-1β secretion, interrupting the autocrine IL-1β loop. The results suggest that Cl- effects are mediated by SGK1, which under Cl- modulation stimulates the secretion of mature IL-1β, in turn, responsible for the upregulation of ROS, CASP1, NLRP3, and IL-1β itself, through autocrine signaling.

PMID:33835494 | DOI:10.1111/imm.13336

Hum Genet. 2021 Apr 8. doi: 10.1007/s00439-021-02272-5. Online ahead of print.

ABSTRACT

Gene therapies for genetic diseases have been sought for decades, and the relatively recent development of the CRISPR/Cas9 gene-editing system has encouraged a new wave of interest in the field. There have nonetheless been significant setbacks to gene therapy, including unintended biological consequences, ethical scandals, and death. The major focus of research has been on technological problems such as delivery, potential immune responses, and both on and off-target effects in an effort to avoid negative clinical outcomes. While the field has concentrated on how we can better achieve gene therapies and gene editing techniques, there has been less focus on when and why we should use such technology. Here we combine discussion of both the technical and ethical barriers to the widespread clinical application of gene therapy and gene editing, providing a resource for gene therapy experts and novices alike. We discuss ethical problems and solutions, using cystic fibrosis and beta-thalassemia as case studies where gene therapy might be suitable, and provide examples of situations where human germline gene editing may be ethically permissible. Using such examples, we propose criteria to guide researchers and clinicians in deciding whether or not to pursue gene therapy as a treatment. Finally, we summarize how current progress in the field adheres to principles of biomedical ethics and highlight how this approach might fall short of ethical rigour using examples in the bioethics literature. Ultimately by addressing both the technical and ethical aspects of gene therapy and editing, new frameworks can be developed for the fair application of these potentially life-saving treatments.

PMID:33834266 | DOI:10.1007/s00439-021-02272-5

Cureus. 2021 Mar 5;13(3):e13716. doi: 10.7759/cureus.13716.

ABSTRACT

Cystic fibrosis is an autosomal recessive disorder caused by a mutation in genes for cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR gene is responsible for the production of sweat, digestive fluids, and mucus, and any mutation in this would lead to the thickening of these secretions. Cystic fibrosis is a multi-organ disorder, but 80% of patients suffer from respiratory problems due to chronic infections most commonly caused by Pseudomonas aeruginosa (P. aeruginosa). Eradication of these infections has become a challenge as P. aeruginosa has developed resistance to multiple antibiotics. In several studies, iron has been shown to play an integral role in biofilm formation, which is the predominant resistance mechanism used by P. aeruginosa to combat antibiotics. The increased iron content in cystic fibrosis patients' sputum samples explains their increased susceptibility to Pseudomonas infections. Hence in this review article, we have used the research data available on therapeutic agents that target iron as an adjuvant treatment for chronic Pseudomonas infection. We systematically screened three databases using focused words and Medical Subject Headings (MeSH) terms for relevant articles. Further, we applied the inclusion and exclusion criteria and performed a thorough quality appraisal. Thirty shortlisted relevant studies were meticulously reviewed. In our opinion, novel therapeutic approaches targeting iron such as iron chelators, gallium, and cefiderocol have potent anti-biofilm properties. Future studies and clinical trials using these approaches in the management of chronic Pseudomonas infection might help in decreasing morbidity and mortality in patients with cystic fibrosis. Exploring these approaches might also help to combat other resistant organisms whose survival is dependent on iron.

PMID:33833927 | PMC:PMC8019538 | DOI:10.7759/cureus.13716

Front Immunol. 2021 Mar 23;12:651060. doi: 10.3389/fimmu.2021.651060. eCollection 2021.

ABSTRACT

In cystic fibrosis (CF) infectious and allergic airway inflammation cause pulmonary exacerbations that destroy the lungs. Staphylococcus aureus is a common long-term colonizer and cause of recurrent airway infections in CF. The pathogen is also associated with respiratory allergy; especially the staphylococcal serine protease-like proteins (Spls) can induce type 2 immune responses in humans and mice. We measured the serum IgE levels specific to 7 proteases of S. aureus by ELISA, targeting 5 Spls (76 CF patients and 46 controls) and the staphopains A and B (16 CF patients and 46 controls). Then we compared cytokine release and phenotype of T cells that had been stimulated with Spls between 5 CF patients and 5 controls. CF patients had strongly increased serum IgE binding to all Spls but not to the staphopains. Compared to healthy controls, their Spl-stimulated T cells released more type 2 cytokines (IL-4, IL-5, IL-13) and more IL-6 with no difference in the secretion of type 1- or type 3 cytokines (IFNγ, IL-17A, IL-17F). IL-10 production was low in CF T cells. The phenotype of the Spl-exposed T cells shifted towards a Th2 or Th17 profile in CF but to a Th1 profile in controls. Sensitization to S. aureus Spls is common in CF. This discovery could explain episodes of allergic inflammation of hitherto unknown causation in CF and extend the diagnostic and therapeutic portfolio.

PMID:33833764 | PMC:PMC8021911 | DOI:10.3389/fimmu.2021.651060

Front Pharmacol. 2021 Mar 23;12:627503. doi: 10.3389/fphar.2021.627503. eCollection 2021.

ABSTRACT

Nitric oxide (NO) is produced by a family of isoenzymes, nitric oxide synthases (NOSs), which all utilize L-arginine as substrate. The production of NO in the lung and airways can play a number of roles during lung development, regulates airway and vascular smooth muscle tone, and is involved in inflammatory processes and host defense. Altered L-arginine/NO homeostasis, due to the accumulation of endogenous NOS inhibitors and competition for substrate with the arginase enzymes, has been found to play a role in various conditions affecting the lung and in pulmonary diseases, such as asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), pulmonary hypertension, and bronchopulmonary dysplasia. Different therapeutic strategies to increase L-arginine levels or bioavailability are currently being explored in pre-clinical and clinical studies. These include supplementation of L-arginine or L-citrulline and inhibition of arginase.

PMID:33833679 | PMC:PMC8022134 | DOI:10.3389/fphar.2021.627503

J Pediatr Pharmacol Ther. 2021;26(3):248-252. doi: 10.5863/1551-6776-26.3.248. Epub 2021 Mar 31.

ABSTRACT

OBJECTIVE: Cystic fibrosis (CF) patients and caregivers are impacted by the number of pharmacological agents and unique administration needs; however, no data currently assesses how medication regimen complexity impacts clinical outcomes in this population. The objective of this study is to evaluate if an association exists between increased medication regimen complexity and clinical endpoints in pediatric patients with CF.

METHODS: This retrospective analysis included all pediatric patients with CF (ages 5-20 years) with at least 2 pharmacist encounters and acceptable pulmonary function tests at our pediatric pulmonary clinic during 2017. Each patient's medication regimen was scored using the validated Medication Regimen Complexity Index (MRCI) tool. The primary outcome was the correlation between MRCI score and lung function. Secondary endpoints included growth, number of infections requiring antibiotics, and hospitalizations.

RESULTS: MRCI scores of the 113 included patients ranged from 2 to 101 points. A negative correlation was found between initial and final MRCI score and initial and final forced expiratory volume in 1 second (FEV1; r = -0.323, p = 0.0005 and r = -0.287, p = 0.0021, respectively). MRCI scores were negatively correlated with BMI percentile for both encounters (r = -0.162 and r = -0.125) but were not significant. Higher MRCI scores were associated with increased use of oral and intravenous antibiotics and hospital admissions.

CONCLUSIONS: Higher MRCI scores are correlated with a significant decrease in FEV1, increased need for antibiotic therapy, and more hospital admissions in pediatric patients with CF. Larger studies are needed to determine if a correlation exists between MRCI score and growth.

PMID:33833625 | PMC:PMC8021245 | DOI:10.5863/1551-6776-26.3.248

Sci Rep. 2021 Apr 8;11(1):7719. doi: 10.1038/s41598-021-87099-w.

ABSTRACT

Vitamin D toxicity is associated with accidental overdoses due to manufacturing or intake errors and its secondary hypercalcemia can result in severe morbidity. Although patients with cystic fibrosis are potentially at increased risk for this intoxication as prescription of vitamin D preparations is a common practice in this population, the frequency of such events is currently unknown. We performed a retrospective analysis of all the files of cystic fibrosis patients followed at the Cliniques universitaires Saint-Luc over a 10-year period, recording 25(OH)- and 1,25(OH)2vitamin D levels as well as demographic data, lung function tests, Pseudomonas aeruginosa infection and results from pharmacological analysis of magistral liposoluble vitamins preparations. A total of 244 patients were included in the study. 13 patients (5%) had serum vitamin D levels corresponding to vitamin D overdose. Patients who had experienced an overdose were more likely to be F508del homozygous or suffer from exocrine pancreatic insufficiency. 2 patients developed significant hypercalcemia necessitating monitoring and hospitalization. Errors in the preparation of magistral liposoluble vitamin pills were identified in several intoxicated patients. Retrospective assessment of the dosing errors with the local pharmacists showed that trituration and dosing errors were their most frequent causes.

PMID:33833284 | DOI:10.1038/s41598-021-87099-w

J Cyst Fibros. 2021 Apr 6:S1569-1993(21)00098-9. doi: 10.1016/j.jcf.2021.03.016. Online ahead of print.

ABSTRACT

Despite being an important patient group, adult cystic fibrosis patients with an FEV1 below 40%predicted have been excluded from clinical trials with elexacaftor/tezacaftor/ivacaftor. We conducted a real-life 3 months follow-up study in 14 adult CF patients (median FEV1 34%predicted) demonstrating significant treatment effects in terms of FEV1 (an increase of 12%predicted at 4 weeks, remaining stable thereafter). Corresponding decreases in lung clearance index LCI (by 31%predicted, down from baseline 247%predicted) and ventilation heterogeneity in the acinar compartment (Sacin) (by 411%predicted, down from baseline 798%predicted) suggest a distinct peripheral lung effect. One patient had intermittent treatment interruptions because of drug-induced liver injury. Our real-life data confirm that treatment with elexacaftor/tezacaftor/ivacaftor is effective in severely obstructive patients, and this is the first study to show time evolution of ventilation distribution improvement, pointing to the peripheral lung as the main site of treatment effect.

PMID:33832855 | DOI:10.1016/j.jcf.2021.03.016