Healthcare (Basel). 2023 Aug 10;11(16):2245. doi: 10.3390/healthcare11162245.

ABSTRACT

Avoidant/Restrictive food intake disorder (ARFID) is a feeding disorder characterized by persistent difficulty eating, such as limited choices of preferred foods, avoidance or restriction of certain foods or food groups, and negative emotions related to eating or meals. Although ARFID mainly affects children, it can also occur in adolescents and adults. ARFID can have serious physical and mental health consequences, including stunted growth, nutritional deficiencies, anxiety, and other psychiatric comorbidities. Despite its increasing importance, ARFID is relatively underrecognized and undertreated in clinical practice. Treatment consists of a multidisciplinary approach involving pediatric gastroenterologists, nutritionists, neuropsychiatrists, and psychologists. However, there are several gaps in the therapeutic approach for this condition, mainly due to the lack of interventional trials and the methodological variability of existing studies. Few studies have explored the nutritional management of ARFID, and no standardized guidelines exist to date. We performed a systematic literature review to describe the different nutritional interventions for children and adolescents diagnosed with ARFID and to assess their efficacy and tolerability. We identified seven retrospective cohort studies where patients with various eating and feeding disorders, including ARFID, underwent nutritional rehabilitation in hospital settings. In all studies, similar outcomes emerged in terms of efficacy and tolerability. According to our findings, the oral route should be the preferred way to start the refeeding protocol, and the enteral route should be generally considered a last resort for non-compliant patients or in cases of clinical instability. The initial caloric intake may be adapted to the initial nutritional status, but more aggressive refeeding regimens appear to be well tolerated and not associated with an increased risk of clinical refeeding syndrome (RS). In severely malnourished patients, however, phosphorus or magnesium supplementation may be considered to prevent the risk of electrolyte imbalance, or RS.

PMID:37628443 | DOI:10.3390/healthcare11162245

Children (Basel). 2023 Jul 31;10(8):1317. doi: 10.3390/children10081317.

ABSTRACT

INTRODUCTION: Oral glucose tolerance testing is recommended for all children with CF older than 9 years, yet compliance remains poor across centers.

METHODS: We performed a small pilot study assessing the glycemic curves and participant satisfaction in seven children and adolescents.

RESULTS: We chose a dextrose-based candy (Nerds®) free of any fat, fiber, gelatin, or corn syrup and performed the candy OGTT 1-4 days following the standard oral dextrose solution OGTT. Glucose values at 120 min were similar between the candy and oral dextrose solution (p = 0.8986).

CONCLUSIONS: Our small pilot suggests that a carefully selected candy alternative may result in similar glycemic OGTT when compared to the standard oral dextrose solution. However, some participants preferred the oral dextrose solution to candy due to having to consume a large volume in a short period of time. This may have significant implications as centers consider candy alternatives to increase OGTT adherence rates.

PMID:37628316 | DOI:10.3390/children10081317

Biomolecules. 2023 Aug 16;13(8):1249. doi: 10.3390/biom13081249.

ABSTRACT

Inherited bone marrow failure syndromes (IBMFSs) include Fanconi anemia, Diamond-Blackfan anemia, Shwachman-Diamond syndrome, dyskeratosis congenita, severe congenital neutropenia, and other rare entities such as GATA2 deficiency and SAMD9/9L mutations. The IBMFS monogenic disorders were first recognized by their phenotype. Exome sequencing has validated their classification, with clusters of gene mutations affecting DNA damage response (Fanconi anemia), ribosome structure (Diamond-Blackfan anemia), ribosome assembly (Shwachman-Diamond syndrome), or telomere maintenance/stability (dyskeratosis congenita). The pathogenetic mechanisms of IBMFSs remain to be characterized fully, but an overarching hypothesis states that different stresses elicit TP53-dependent growth arrest and apoptosis of hematopoietic stem, progenitor, and precursor cells. Here, we review the IBMFSs and propose a role for pro-inflammatory cytokines, such as TGF-β, IL-1β, and IFN-α, in mediating the cytopenias. We suggest a pathogenic role for cytokines in the transformation to myeloid neoplasia and hypothesize a role for anti-inflammatory therapies.

PMID:37627314 | DOI:10.3390/biom13081249

Cells. 2023 Aug 12;12(16):2057. doi: 10.3390/cells12162057.

ABSTRACT

Pulmonary bacterial infections present a significant health risk to those with chronic respiratory diseases (CRDs) including cystic fibrosis (CF) and chronic-obstructive pulmonary disease (COPD). With the emergence of antimicrobial resistance (AMR), novel therapeutics are desperately needed to combat the emergence of resistant superbugs. Phage therapy is one possible alternative or adjunct to current antibiotics with activity against antimicrobial-resistant pathogens. How phages are administered will depend on the site of infection. For respiratory infections, a number of factors must be considered to deliver active phages to sites deep within the lung. The inhalation of phages via nebulization is a promising method of delivery to distal lung sites; however, it has been shown to result in a loss of phage viability. Although preliminary studies have assessed the use of nebulization for phage therapy both in vitro and in vivo, the factors that determine phage stability during nebulized delivery have yet to be characterized. This review summarizes current findings on the formulation and stability of liquid phage formulations designed for nebulization, providing insights to maximize phage stability and bactericidal activity via this delivery method.

PMID:37626867 | DOI:10.3390/cells12162057

Am J Transplant. 2023 Aug 23:S1600-6135(23)00652-4. doi: 10.1016/j.ajt.2023.08.014. Online ahead of print.

ABSTRACT

The Acute Rejection Score (A-score) in lung transplant recipients, calculated as the average of acute cellular rejection A-grades across transbronchial biopsies, summarises the cumulative burden of rejection over time. We assessed the association between A-score and transplant outcomes in two geographically distinct cohorts. The primary cohort included 772 double lung transplant recipients. The analysis was repeated in 300 patients from an independent comparison cohort. Time-dependent multivariable Cox models were constructed to evaluate the association between A-score and CLAD or graft failure. Landmark analyses were performed with A-score calculated at 6 and 12 months post-transplant. In the primary cohort, no association was found between A-score and graft outcome. However, in the comparison cohort, time A-score was associated with CLAD both as a time-dependent variable (HR 1.51, p < 0.01), and when calculated at 6 and 12 months post-transplant. The A-score can be a useful predictor of lung transplant outcomes in some settings but is not generalizable across all centres; its utility as a prognostication tool is therefore limited.

PMID:37625646 | DOI:10.1016/j.ajt.2023.08.014

J Ethnopharmacol. 2023 Aug 23:117077. doi: 10.1016/j.jep.2023.117077. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Resina Draconis (RD) is the red resin of Dracaena cochinchinensis (Lour.) S.C. Chen and most used as a hemostatic drug in traditional Chinese medicine. Recent studies have reported that RD has a therapeutic effect on gastrointestinal diseases. Loureirin A, B, and C (LA, LB, and LC) are dihydrochalcone compounds isolated from RD.

AIM OF THE STUDY: Dehydration is the primary cause of death in rotaviral diarrhea. Inhibition of Ca2+-activated Cl- channels (CaCCs)-mediated Cl- secretion significantly reduced fluid secretion in rotaviral diarrhea. RD was used to treat digestive diseases such as diarrhea and abdominal pain; however, the pharmacological mechanism remains unclear. This study investigated the effects of RD and loureirin on intestinal Cl- channels and their therapeutic effects on rotavirus-induced diarrhea, aiming to reveal RD's molecular basis, targets, and mechanisms for treating rotaviral diarrhea.

MATERIALS AND METHODS: Cell-based fluorescence quenching assays were used to examine the effect of RD and loureirin on Cl- channels activity. Electrophysiological properties were tested using short-circuit current experiments in epithelial cells or freshly isolated mouse intestinal tissue. Fecal water content, intestinal peristalsis rate, and smooth muscle contraction were measured in neonatal mice infected with SA-11 rotavirus before and after LC treatment or adult mice.

RESULTS: RD, LA, LB, and LC inhibited CaCCs-mediated Cl- current in HT-29 cells and colonic epithelium. The inhibitory effect of LC on CaCCs was primarily on the apical side in epithelial cells, which may be partially produced by affecting cytoplasmic Ca2+ levels. LC significantly inhibited TMEM16A-mediated Cl- current. Characterization studies revealed that LC inhibited basolateral K+ channel activity without affecting Na+/K+-ATPase activity in the colonic epithelium. Although LC activated the cystic fibrosis transmembrane regulator in epithelial cells, its effect was not apparent in colonic epithelium. In vivo, LC significantly reduced the fecal water content, intestinal peristalsis rate, and smooth muscle contraction of mice infected with rotavirus.

CONCLUSION: RD and its active compound LC inhibit intestinal CaCCs activity, which might mediate the anti-rotaviral diarrheal effect of RD.

PMID:37625605 | DOI:10.1016/j.jep.2023.117077

Cell Stem Cell. 2023 Aug 18:S1934-5909(23)00281-3. doi: 10.1016/j.stem.2023.07.014. Online ahead of print.

ABSTRACT

Life-long reconstitution of a tissue's resident stem cell compartment with engrafted cells has the potential to durably replenish organ function. Here, we demonstrate the engraftment of the airway epithelial stem cell compartment via intra-airway transplantation of mouse or human primary and pluripotent stem cell (PSC)-derived airway basal cells (BCs). Murine primary or PSC-derived BCs transplanted into polidocanol-injured syngeneic recipients give rise for at least two years to progeny that stably display the morphologic, molecular, and functional phenotypes of airway epithelia. The engrafted basal-like cells retain extensive self-renewal potential, evident by the capacity to reconstitute the tracheal epithelium through seven generations of secondary transplantation. Using the same approach, human primary or PSC-derived BCs transplanted into NOD scid gamma (NSG) recipient mice similarly display multilineage airway epithelial differentiation in vivo. Our results may provide a step toward potential future syngeneic cell-based therapy for patients with diseases resulting from airway epithelial cell damage or dysfunction.

PMID:37625411 | DOI:10.1016/j.stem.2023.07.014

Pathogens. 2023 Aug 17;12(8):1053. doi: 10.3390/pathogens12081053.

ABSTRACT

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen and the leading cause of infection in patients with cystic fibrosis (CF). The ability of P. aeruginosa to evade host responses and develop into chronic infection causes significant morbidity and mortality. Several mouse models have been developed to study chronic respiratory infections induced by P. aeruginosa, with the bead agar model being the most widely used. However, this model has several limitations, including the requirement for surgical procedures and high mortality rates. Herein, we describe novel and adapted biologically relevant models of chronic lung infection caused by P. aeruginosa. Three methods are described: a clinical isolate infection model, utilising isolates obtained from patients with CF; an incomplete antibiotic clearance model, leading to bacterial bounce-back; and the establishment of chronic infection; and an adapted water bottle chronic infection model. These models circumvent the requirement for a surgical procedure and, importantly, can be induced with clinical isolates of P. aeruginosa and in wild-type mice. We also demonstrate successful induction of chronic infection in the transgenic βENaC murine model of CF. We envisage that the models described will facilitate the investigations of host and microbial factors, and the efficacy of novel antimicrobials, during chronic P. aeruginosa respiratory infections.

PMID:37624013 | DOI:10.3390/pathogens12081053

Metabolites. 2023 Aug 9;13(8):932. doi: 10.3390/metabo13080932.

ABSTRACT

Most studies on single ventricle (SV) circulation take a physiological or anatomical approach. Although there is a tight coupling between cardiac contractility and metabolism, the metabolic perspective on this patient population is very recent. Early findings point to major metabolic disturbances, with both impaired glucose and fatty acid oxidation in the cardiomyocytes. Additionally, Fontan patients have systemic metabolic derangements such as abnormal glucose metabolism and hypocholesterolemia. Our literature review compares the metabolism of patients with a SV circulation after Fontan palliation with that of patients with a healthy biventricular (BV) heart, or different subtypes of a failing BV heart, by Pubmed review of the literature on cardiac metabolism, Fontan failure, heart failure (HF), ketosis, metabolism published in English from 1939 to 2023. Early evidence demonstrates that SV circulation is not only a hemodynamic burden requiring staged palliation, but also a metabolic issue with alterations similar to what is known for HF in a BV circulation. Alterations of fatty acid and glucose oxidation were found, resulting in metabolic instability and impaired energy production. As reported for patients with BV HF, stimulating ketone oxidation may be an effective treatment strategy for HF in these patients. Few but promising clinical trials have been conducted thus far to evaluate therapeutic ketosis with HF using a variety of instruments, including ketogenic diet, ketone esters, and sodium-glucose co-transporter-2 (SGLT2) inhibitors. An initial trial on a small cohort demonstrated favorable outcomes for Fontan patients treated with SGLT2 inhibitors. Therapeutic ketosis is worth considering in the treatment of Fontan patients, as ketones positively affect not only the myocardial energy metabolism, but also the global Fontan physiopathology. Induced ketosis seems promising as a concerted therapeutic strategy.

PMID:37623876 | DOI:10.3390/metabo13080932

mSystems. 2023 Aug 25:e0049123. doi: 10.1128/msystems.00491-23. Online ahead of print.

ABSTRACT

Epidemic strains of Pseudomonas aeruginosa often have increased levels of antibiotic resistance, and these resistance phenotypes are difficult to predict. We used quantitative proteomics to compare the responses of laboratory strain PAO1 and two isolates of the Liverpool epidemic strain (LES) to four antibiotics and hydrogen peroxide. The majority of proteome changes were unique to either one isolate or treatment, but smaller groups of proteins were differentially abundant in more than one sample. Proteins in these shared adaptive responses represent promising avenues for further investigation to understand the contribution of these proteins to resistance and their potential as targets for novel treatments. We observed the largest overlap between the proteome profiles of PAO1 challenged with tobramycin and hydrogen peroxide, and our data support previous work suggesting a role for heat shock protein IbpA in response to tobramycin. Our proteome profiling uncovered extensive changes in LESB58 in response to carbenicillin, with more than 1,000 proteins significantly changed in abundance. This included unique changes in the abundance of proteins involved in cell wall synthesis and division. We used phase contrast microscopy to check for corresponding changes in cell morphology and show that LESB58 maintained shorter cell lengths under treatment with β-lactams. We propose that the ability to maintain the processes of cell wall synthesis and division through changes in protein abundances contributes to the high levels of β-lactam resistance in LESB58. IMPORTANCE Pseudomonas aeruginosa is an important pathogen often associated with hospital-acquired infections and chronic lung infections in people with cystic fibrosis. P. aeruginosa possesses a wide array of intrinsic and adaptive mechanisms of antibiotic resistance, and the regulation of these mechanisms is complex. Label-free quantitative proteomics is a powerful tool to compare susceptible and resistant strains of bacteria and their responses to antibiotic treatments. Here we compare the proteomes of three isolates of P. aeruginosa with different antibiotic resistance profiles in response to five challenge conditions. We uncover unique and shared proteome changes for the widely used laboratory strain PAO1 and two isolates of the Liverpool epidemic strain of P. aeruginosa, LESlike1 and LESB58. Our data set provides insight into antibiotic resistance in clinically relevant Pseudomonas isolates and highlights proteins, including those with uncharacterized functions, which can be further investigated for their role in adaptive responses to antibiotic treatments.

PMID:37623324 | DOI:10.1128/msystems.00491-23

Genet Med. 2023 Aug 22:100966. doi: 10.1016/j.gim.2023.100966. Online ahead of print.

ABSTRACT

PURPOSE: Automated use of electronic health records may aid in decreasing the diagnostic delay for rare diseases. The phenotype risk score (PheRS) is a weighted aggregate of syndromically related phenotypes that measures the similarity between an individual's conditions and features of a disease. For some diseases, there are individuals without a diagnosis of that disease who have scores similar to diagnosed patients. These individuals may have that disease but not yet be diagnosed.

METHODS: We calculated the PheRS for cystic fibrosis (CF) for 965,626 subjects in the Vanderbilt University Medical Center electronic health record.

RESULTS: Of the 400 subjects with the highest PheRS for CF, 248 (62%) had been diagnosed with CF. Twenty-six of the remaining particpants, those who were alive and had DNA available in the linked DNA biobank, underwent clinical review and sequencing analysis of CFTR and SERPINA1. This uncovered a potential diagnosis for two subjects, one with CF and one with alpha-1-antitrypsin deficiency. An additional seven subjects had pathogenic or likely pathogenic variants, two in CFTR and five in SERPINA1.

CONCLUSION: These findings may be clinically actionable for the providers caring for these patients. Importantly, this study highlights feasibility and challenges for future implications of this approach.

PMID:37622442 | DOI:10.1016/j.gim.2023.100966

J Paediatr Child Health. 2023 Aug 25. doi: 10.1111/jpc.16480. Online ahead of print.

NO ABSTRACT

PMID:37621236 | DOI:10.1111/jpc.16480

PLoS Pathog. 2023 Aug 24;19(8):e1011559. doi: 10.1371/journal.ppat.1011559. eCollection 2023 Aug.

ABSTRACT

Mycobacterium abscessus (Mabs) drives life-shortening mortality in cystic fibrosis (CF) patients, primarily because of its resistance to chemotherapeutic agents. To date, our knowledge on the host and bacterial determinants driving Mabs pathology in CF patient lung remains rudimentary. Here, we used human airway organoids (AOs) microinjected with smooth (S) or rough (R-)Mabs to evaluate bacteria fitness, host responses to infection, and new treatment efficacy. We show that S Mabs formed biofilm, and R Mabs formed cord serpentines and displayed a higher virulence. While Mabs infection triggers enhanced oxidative stress, pharmacological activation of antioxidant pathways resulted in better control of Mabs growth and reduced virulence. Genetic and pharmacological inhibition of the CFTR is associated with better growth and higher virulence of S and R Mabs. Finally, pharmacological activation of antioxidant pathways inhibited Mabs growth, at least in part through the quinone oxidoreductase NQO1, and improved efficacy in combination with cefoxitin, a first line antibiotic. In conclusion, we have established AOs as a suitable human system to decipher mechanisms of CF-driven respiratory infection by Mabs and propose boosting of the NRF2-NQO1 axis as a potential host-directed strategy to improve Mabs infection control.

PMID:37619220 | DOI:10.1371/journal.ppat.1011559

Respir Care. 2023 Feb;68(2):284-285. doi: 10.4187/respcare.10832.

NO ABSTRACT

PMID:37615522 | DOI:10.4187/respcare.10832

Pharmacotherapy. 2023 Aug;43(8):740-777. doi: 10.1002/phar.2842.

ABSTRACT

Intravenous β-lactam antibiotics remain a cornerstone in the management of bacterial infections due to their broad spectrum of activity and excellent tolerability. β-lactams are well established to display time-dependent bactericidal activity, where reductions in bacterial burden are directly associated with the time that free drug concentrations remain above the minimum inhibitory concentration (MIC) of the pathogen during the dosing interval. In an effort to take advantage of these bactericidal characteristics, prolonged (extended and continuous) infusions (PIs) can be applied during the administration of intravenous β-lactams to increase time above the MIC. PI dosing regimens have been implemented worldwide, but implementation is inconsistent. We report consensus therapeutic recommendations for the use of PI β-lactams developed by an expert international panel with representation from clinical pharmacy and medicine. This consensus guideline provides recommendations regarding pharmacokinetic and pharmacodynamic targets, therapeutic drug-monitoring considerations, and the use of PI β-lactam therapy in the following patient populations: severely ill and nonseverely ill adult patients, pediatric patients, and obese patients. These recommendations provide the first consensus guidance for the use of β-lactam therapy administered as PIs and have been reviewed and endorsed by the American College of Clinical Pharmacy (ACCP), the British Society for Antimicrobial Chemotherapy (BSAC), the Cystic Fibrosis Foundation (CFF), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Diseases Society of America (IDSA), the Society of Critical Care Medicine (SCCM), and the Society of Infectious Diseases Pharmacists (SIDP).

PMID:37615245 | DOI:10.1002/phar.2842

Pharmacotherapy. 2023 Aug;43(8):736-739. doi: 10.1002/phar.2844.

ABSTRACT

Intravenous β-lactam antibiotics remain a cornerstone in the management of bacterial infections due to their broad spectrum of activity and excellent tolerability. β-lactams are well established to display time-dependent bactericidal activity, where reductions in bacterial burden are directly associated with the time that free drug concentrations remain above the minimum inhibitory concentration (MIC) of the pathogen during the dosing interval. In an effort to take advantage of these bactericidal characteristics, prolonged (extended and continuous) infusions (PI) can be applied during the administration of intravenous β-lactams to increase time above the MIC. PI dosing regimens have been implemented worldwide, but implementation is inconsistent. We report consensus therapeutic recommendations for the use of β-lactam PI developed by an expert international panel with representation from clinical pharmacy and medicine. This consensus guideline provides recommendations regarding pharmacokinetic and pharmacodynamic targets, therapeutic drug monitoring considerations, and the use of PI β-lactam therapy in the following patient populations: severely ill and nonseverely ill adult patients, pediatric patients, and obese patients. These recommendations provide the first consensus guidance for the use of β-lactam therapy administered as PIs and have been reviewed and endorsed by the American College of Clinical Pharmacy (ACCP), the British Society for Antimicrobial Chemotherapy (BSAC), the Cystic Fibrosis Foundation (CFF), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Diseases Society of America (IDSA), the Society of Critical Care Medicine (SCCM), and the Society of Infectious Diseases Pharmacists (SIDP).

PMID:37615244 | DOI:10.1002/phar.2844

J Pers. 2023 Aug 24. doi: 10.1111/jopy.12877. Online ahead of print.

ABSTRACT

OBJECTIVES: We tested whether generalized beliefs that the world is safe, abundant, pleasurable, and progressing (termed "primal world beliefs") are associated with several objective measures of privilege.

METHODS: Three studies (N = 16,547) tested multiple relationships between indicators of privilege-including socioeconomic status, health, sex, and neighborhood safety-and relevant world beliefs, as well as researchers and laypeople's expectations of these relationships. Samples were mostly from the USA and included general population samples (Study 2) as well as focused samples of academic researchers (Study 1) and people who had experienced serious illness or trauma (Study 3).

RESULTS: Studies 1-2 found mostly negligible relationships between world beliefs and indicators of privilege, which were invariably lower than researcher predictions (e.g., instead of the expected r = 0.33, neighborhood affluence correlated with Abundant world belief at r = 0.01). Study 3 found that people who had experienced serious illness (cancer, cystic fibrosis) only showed modest differences in beliefs from controls.

CONCLUSIONS: While results do not preclude that some individuals' beliefs were meaningfully affected by life events, they imply that such changes are smaller or less uniform than widely believed and that knowing a person's demographic background may tell us relatively little about their beliefs (and vice versa).

PMID:37614186 | DOI:10.1111/jopy.12877

BMC Health Serv Res. 2023 Aug 23;23(1):901. doi: 10.1186/s12913-023-09861-2.

ABSTRACT

BACKGROUND: Nationwide data for children for short-stay hospitalisation (SSH) and associated factors are scarce. This retrospective study of children in France < 18 years of age followed after their birth or birthday in 2018 focused on at least one annual SSH, stay < 1 night or ≥ 1 night, or 30-day readmission ≥ 1 night.

METHODS: Children were selected from the national health data system (SNDS), which includes data on long-term chronic disease (LTD) status with full reimbursement and complementary universal coverage based on low household income (CMUC). Uni and multivariate quasi-Poisson regression were applied for each outcome.

RESULTS: Among 13.211 million children (94.4% population, 51.2% boys), CMUC was identified for 17.5% and at least one LTD for 4% (0-<1 year: 1.5%; 14-<18 year: 5.2%). The most frequent LTDs were pervasive developmental diseases (0.53%), asthma (0.24%), epilepsy (0.17%), and type 1 diabetes (0.15%). At least one SSH was found for 8.8%: SSH < 1 night (4.9%), SSH ≥ 1 night (4.5%), readmission (0.4%). Children with at least one SSH were younger (median 6 vs. 9 years) and more often had CMUC (21%), a LTD (12%), an emergency department (ED) visit (56%), or various primary healthcare visits than all children. Those with a SSH ≥1 night vs. < 1 night were older (median: 9 vs. 4 years). They had the same frequency of LTD (13.4%) but more often an ED visit (78% vs. 42%). Children with readmissions were younger (median 3 years). They had the highest levels of CMUC (29.3%), LTD (34%), EDs in their municipality (35% vs. 29% for the whole population) and ED visits (87%). In adjusted analysis, each outcome was significantly less frequent among girls than boys and more frequent for children with CMUC. LTDs with the largest association with SSH < 1 night were cystic fibrosis, sickle cell diseases (SCD), diabetes type 1, those with SSH ≥1 night type 1 diabetes epilepsy and SCD, and those for readmissions lymphoid leukaemia, malignant neoplasm of the brain, and SCD. Among all SSH admissions of children < 10 years, 25.8% were potentially preventable.

CONCLUSION: Higher SSH and readmission rates were found for children with certain LTD living in low-income households, suggesting the need or increase of specific policy actions and research.

PMID:37612699 | DOI:10.1186/s12913-023-09861-2

Curr Opin Pulm Med. 2023 Aug 24. doi: 10.1097/MCP.0000000000001005. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: To discuss the existing health inequities in people with cystic fibrosis (CF) and how the recent development of cystic fibrosis transmembrane regulator (CFTR) modulators may impact these inequities.

RECENT FINDINGS: People with CF (pwCF) from low socioeconomic status (SES) have more pulmonary exacerbations, worse nutritional status, lower pulmonary function, and an increased mortality rate with less access to lung transplantation. pwCF who identify as racial and ethnic minorities have earlier mortality, lower lung function, are less likely to be detected on newborn screening resulting in a delayed diagnosis, are underrepresented in clinic trials, and less likely to be eligible for a CFTR modulator. Female sex is associated with more pulmonary exacerbations and earlier mortality. Sexual gender minorities are a vulnerable population with worse health outcomes, and more research is needed in CF. CFTR modulators are inaccessible to low to middle-income countries due to significant cost burden.

SUMMARY: People with CF from low SES, racial and ethnic minorities, female sex, and sexual gender minorities face health inequities. CFTR modulator use will further widen existing health inequities given the unequal access to modulators based on nonqualifying genetics and exorbitant cost restricting use both on an individual and global level.

PMID:37611037 | DOI:10.1097/MCP.0000000000001005

Curr Opin Pulm Med. 2023 Aug 24. doi: 10.1097/MCP.0000000000001006. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Cystic fibrosis is a genetic disease that increases risk of death from respiratory failure because of impairment in mucociliary clearance. Complex daily care regimens including medications and airway clearance techniques (ACTs) aim to preserve lung function and alleviate symptoms for people with cystic fibrosis (pwCF). The success of highly effective modulator therapy (HEMT) permits evaluation of treatment simplification. In this review, we evaluate adjustments made in daily respiratory care among pwCF taking HEMT and the feasibility of treatment simplification.

RECENT FINDINGS: Treatment simplification has been identified as a top priority among pwCF, with recent studies showing pwCF are willing to sacrifice mild to moderate amounts of lung function and longevity to reduce treatment burden. Retrospective studies have shown that patients taking HEMT with better baseline lung function have lower adherence to and prescription of inhaled medications. A randomized, controlled trial found that short-term discontinuation of dornase alfa or hypertonic saline was clinically noninferior to continuation of these medications. Major knowledge gaps remain about withdrawing ACTs.

SUMMARY: This review highlights trials evaluating the feasibility of treatment simplification among pwCF taking HEMT. More data is needed to evaluate approaches to simplification in this phenotypically diverse patient population.

PMID:37611027 | DOI:10.1097/MCP.0000000000001006