Screening for hearing loss in adults with CF: does it make sense?

Thorax. 2020 Jul 09;:

Authors: Andrew J

PMID: 32646893 [PubMed - as supplied by publisher]

Clinical Effectiveness of Lumacaftor/Ivacaftor in Cystic Fibrosis Patients Homozygous for F508del-CFTR.

Ann Am Thorac Soc. 2020 Jul 09;:

Authors: Sagel SD, Khan U, Heltshe SL, Clancy JP, Borowitz D, Gelfond D, Donaldson SH, Moran A, Ratjen F, VanDalfsen JM, Rowe SM, PROSPECT Investigators of the Cystic Fibrosis Foundation Therapeutics Development Network

Abstract
RATIONALE: The combination of lumacaftor and ivacaftor (LUM/IVA) is an approved cystic fibrosis transmembrane conductance regulator (CFTR) modulator treatment for homozygous F508del CF patients.
OBJECTIVE: To evaluate the effectiveness of LUM/IVA in children (≥ 6 years) and adults (> 18 years) in a post-approval setting.
METHODS: This longitudinal cohort study, performed at 38 centers in the United States CF Therapeutics Development Network, enrolled homozygous F508del CF patients ages 6 and above with no prior exposure to LUM/IVA. Study assessments were performed at baseline, 1, 3, 6 and 12 months after LUM/IVA initiation.
RESULTS: 193 patients initiated LUM/IVA and 85% completed the study through 1 year. Baseline mean percent predicted forced expiratory volume in 1 second (ppFEV1) was 85 (SD=22.4) in this cohort. No statistically significant change in ppFEV1 was observed from baseline to any of the follow-up time points, with a mean absolute change at 12 months of -0.3 (95%CI: -1.8, 1.2). Body mass index improved from baseline to 12 months (mean change=0.8 kg/m2, p<0.001). Sweat chloride decreased from baseline to 1 month (mean change= -18.5 mmol/L, 95% CI = (-20.7, -16.3), p<0.001), and these reductions were sustained through the study period. There were no significant changes in hospitalization rate for pulmonary exacerbations and Pseudomonas aeruginosa infection status with treatment.
CONCLUSIONS: In this real-world multicenter cohort of children and adults, LUM/IVA treatment was associated with significant improvements in growth and reductions in sweat chloride, without statistically significant or clinically meaningful changes in lung function, hospitalization rates, or P. aeruginosa infection.

PMID: 32644818 [PubMed - as supplied by publisher]

Implementation Strategies for Depression and Anxiety Screening in a Pediatric Cystic Fibrosis Center: A Quality Improvement Project.

Pediatr Pulmonol. 2020 Jul 09;:

Authors: Liu FF, Lew A, Andes E, McNamara S, Cassidy J, Whitmore S, Plunkett R, Ong T

Abstract
BACKGROUND: Guidelines to integrate mental health screening (MHS) into cystic fibrosis (CF) care has increased adoption across US and European CF Centers, however there has been limited discussion on specific strategies for implementation.
OBJECTIVE: Share key strategies that led to successful MHS implementation in one pediatric CF center and report implementation and screening outcomes.
METHODS: Parent partners, mental health experts from the Department of Psychiatry, and the CF clinic team co-designed interventions to support 3 major stakeholders: (1) patients and families (2) clinic team, and (3) hospital system. The mental health coordinator approached patients (12 and older) to introduce MHS and administered screening and reviewed results using an electronic tablet and digital measurement feedback system. We used strategies that promoted visibility of screening progress and sharing of data with hospital administration. Descriptive statistics were used to assess prevalence of clinically significant symptoms of anxiety and depression and symptom severity within our sample.
RESULTS: Over the first 2 years of the project, we exceeded our goal of screening 80% of eligible patients per year (80-95% screened) and are on a similar trajectory within the first 7 months of Year-3. We identified high prevalence of clinically significant symptoms of depression (16%) and anxiety (14%) similar to those found in other chronic illness populations. These data helped us advocate hospital leadership to support the development of new mental health services to address identified needs at our center.
CONCLUSION: Leveraging co-production to address stakeholder needs led to successful implementation of a sustainable MHS process. This article is protected by copyright. All rights reserved.

PMID: 32644305 [PubMed - as supplied by publisher]

Is Endoscopic Sinus Surgery Beneficial Post Lung Transplant in Cystic Fibrosis Patients?

Laryngoscope. 2020 Jul 09;:

Authors: Hughes A, Adil EA

PMID: 32644240 [PubMed - as supplied by publisher]

Retinal Whitening After Lung Transplant for Cystic Fibrosis.

JAMA Ophthalmol. 2020 Jul 09;:

Authors: Conrady CD, Demirci H, Wubben TJ

PMID: 32644113 [PubMed - as supplied by publisher]

Inhalable nano-composite microparticles with enhanced dissolution and superior aerosol performance.

Mol Pharm. 2020 Jul 09;:

Authors: Zhu C, Chen J, Yu S, Que C, Taylor LS, Tan W, Wu C, Zhou QT

Abstract
Previous studies have shown that combining colistin (Col), a cationic polypeptide antibiotic, with ivacaftor (Iva), a cystic fibrosis (CF) drug, could achieve synergistic antibacterial effects against Pseudomonas aeruginosa. The purpose of this study was to develop dry powder inhaler (DPI) formulations for co-delivery of Col and Iva, aiming to treat CF and lung infection simultaneously. In order to improve solubility and dissolution for the water insoluble Iva, Iva was encapsulated into bovine serum albumin (BSA) nanoparticles (Iva-BSA-NPs). Inhalable composite microparticles of Iva-BSA-NPs were produced by spray-freeze-drying using water-soluble Col as the matrix material and L-leucine as an aerosol enhancer. The optimal formulation showed irregular-shaped morphology with fine particle fraction (FPF) values of 73.8 ± 5.2% for Col and 80.9 ± 4.1% for Iva. Correlations between "D×√(ρ_tapped )" and FPF were established for both Iva and Col. The amorphous solubility of Iva is 66 times higher than the crystalline solubility in the buffer. Iva-BSA-NPs were amorphous and remained in the amorphous state after spray-freeze-drying as examined by powder X-ray diffraction. In-vitro dissolution profiles of the selected DPI formulation indicated that Col and Iva were almost completely released within 3 hours, which was substantially faster regarding Iva release than the jet milled physical mixture of the two drugs. In summary, this study developed a novel inhalable nano-composite microparticle using a synergistic water-soluble drug as the matrix material, which achieved reduced use of excipients for high-dose medications, improved dissolution rate for the water-insoluble drug and superior aerosol performance.

PMID: 32643939 [PubMed - as supplied by publisher]

Airway complications after lung transplantation: benefit of a conservative bronchoscopy strategy.

J Thorac Dis. 2020 May;12(5):2625-2634

Authors: Patoir A, Luchez A, Tiffet O, Vercherin P, Grima R, Tronc F, Philit F, Mornex JF, Vergnon JM, Maury JM

Abstract
Background: After lung transplantation (LT), between 2% and 25% of bronchial anastomoses develop complications requiring therapeutic intervention. The status of healing of both bronchial anastomoses and downhill airways are well described by the French consensual MDS standardized grading system (Macroscopic, Diameter, Suture). We analyzed risks factors for airway complications (AC) after transplantation and the way we managed them. We report here our challenging method of early rigid bronchoscopic intervention with airway stenting on bronchial healing.
Methods: All single center consecutives LTs were retrospectively analyzed between 2010-2016. Patient-level data (demographic, peri-operative data) and anastomosis-level data (surgical parameters, bronchoscopy findings) were monitored. The incidence and contributive factors of ACs are reported. We also reported modalities of the conservative treatment and outcome.
Results: A total of 121 LTs were performed, 39 single-lung and 82 bilateral sequential LT. Main indication for LT were cystic fibrosis (45%) and emphysema (25%) and 58 were male patients (n=70). After a waiting period of healing, 28 patients presented AC on 41 anastomoses (prevalence: 23%). A multivariate analysis found as contributive factors of ACs, post-operative infection by Aspergillus [odds ratio (OR) 2.7, 95% confidence interval (CI): 1.08-6.75; P=0.033] at the patient level, and at the anastomosis level, emphysema (OR 2.4, 95% CI: 1.02-5.6; P=0.045), early dehiscence (OR 11.2, 95% CI: 1.7-76; P=0.01) and cold ischemia time >264 min (OR 2.45, 95% CI: 1.08-5.6; P=0.03). All the 41 ACs were managed conservatively with rigid bronchoscopy (range, 1-10), 41 stents (21 in silicone and 20 fully-covered Silicone Expandable Metallic Stents) without major complication. Two AC were still under regular bronchoscopic care and silicone stenting for long left bronchus reason. No surgical intervention was needed. The 2-years overall survival rate where not different between AC group and controls, respectively 85% and 81%.
Conclusions: Airway healing after transplantation remains a scalable process and the French consensual MDS classification helped us for therapeutic decisions. Rigid bronchoscopy and safety use of current stenting devices may have the pivotal role in the conservative management of ACs, avoiding perilous situation of surgery for AC. Despite a high rate of AC, their favorable evolution may be explained by the cautious care of airway healing and maybe by the use of the Celsior antioxidant solution.

PMID: 32642170 [PubMed]

Management of Refractory Distal Intestinal Obstruction Syndrome With Ileum Installation of a Hyperosmolar Solution.

J Pediatr Pharmacol Ther. 2020;25(5):467

Authors: Gokce S, Tutak E, Sarimurat N

PMID: 32641920 [PubMed]

Therapeutic Drug Monitoring of Inhaled Tobramycin in a Post-Hematopoietic Cell Transplant Patient With Bronchiolitis Obliterans and End-Stage Renal Disease.

J Pediatr Pharmacol Ther. 2020;25(5):451-454

Authors: Trone DJ, Hall EA

Abstract
There are no widely accepted dose alterations for inhaled tobramycin in the setting of renal dysfunction, and serum concentrations are not typically monitored. Herein we describe a case report of a 16-year-old female with a history of 2 hematopoietic cell transplants and a kidney transplant who received inhaled tobramycin for chronic Pseudomonas aeruginosa management. The patient developed chronic kidney disease, and tobramycin concentrations were monitored. Initially she received a reduced dose of inhaled tobramycin, with repeated doses based on serum concentrations. The dose was increased, but serum concentrations obtained the following day remained higher than desired, leading to a suspicion of delayed systemic absorption. Tobramycin administration was changed from immediately prior to dialysis to the evening prior to the next day's dialysis session, and serum concentrations were consistently <1 mg/L postdialysis. In conclusion, systemic absorption of inhaled tobramycin in non-cystic fibrosis (CF) patients may differ compared to that observed in CF patients. Renal dysfunction may lead to systemic accumulation of inhaled tobramycin, and the timing of inhaled tobramycin administration with respect to dialysis has a potentially significant influence on drug clearance. Thus, monitoring may be required. Further cases are required to verify these observations.

PMID: 32641916 [PubMed]

Practitioner Due Diligence: Real-World Lumacaftor/Ivacaftor Use.

J Pediatr Pharmacol Ther. 2020;25(5):431-436

Authors: Stephan EM, Nemastil CJ, Salvator A, Gemma S, Dilaveris CJ, Rice A, Sakellaris KT, Novak KJ, McCoy KS

Abstract
OBJECTIVE: Previous trials evaluated the efficacy of lumacaftor/ivacaftor in Phe508del homozygotes. These trials are limited by manufacturer sponsorship and were conducted under strict protocol. Additionally, this therapy is costly and does not allow for reduction in daily cystic fibrosis therapies. This study assessed the efficacy of lumacaftor/ivacaftor therapy and its effect on health care utilization in a real-world setting.
METHODS: Retrospective chart review comparing the first 12 months of therapy to the 24 months prior was conducted to evaluate the impact of lumacaftor/ivacaftor on pulmonary function following a streamlined process for therapy introduction. The impact on body mass index and healthcare utilization were also evaluated. The following measurements were assessed: percent predicted forced expiratory volume in 1 second, body mass index and z-scores, number of admissions, length of stay, number of emergency department visits.
RESULTS: Mean ppFEV1 was improved for the first 12 months on lumacaftor/ivacaftor treatment when compared with the 24 months prior: 78.8 (95% CI: 72.6, 84.9) vs 76.2 (95% CI: 70.1, 82.3) (p = 0.03). Body mass index significantly improved (patients ≥20 years), but improvement in BMI z-score (patients <20 years) was not significant. Number of admissions and LOS were significantly decreased, but ED visits were not.
CONCLUSIONS: Lumacaftor/ivacaftor is effective for improving ppFEV1 and BMI and for reducing health care utilization. However, this small reduction does not overcome the financial cost of treatment. Long-term outcomes and use must be studied to determine the overall effect of this therapy on cystic fibrosis interventions and their costs.

PMID: 32641913 [PubMed]

Investigating REPAIRv2 as a Tool to Edit CFTR mRNA with Premature Stop Codons.

Int J Mol Sci. 2020 Jul 06;21(13):

Authors: Melfi R, Cancemi P, Chiavetta R, Barra V, Lentini L, Di Leonardo A

Abstract
Cystic fibrosis (CF) is caused by mutations in the gene encoding the transmembrane conductance regulator (CFTR) protein. Some CF patients are compound heterozygous or homozygous for nonsense mutations in the CFTR gene. This implies the presence in the transcript of premature termination codons (PTCs) responsible for a truncated CFTR protein and a more severe form of the disease. Aminoglycoside and PTC124 derivatives have been used for the read-through of PTCs to restore the full-length CFTR protein. However, in a precision medicine framework, the CRISPR/dCas13b-based molecular tool "REPAIRv2" (RNA Editing for Programmable A to I Replacement, version 2) could be a good alternative to restore the full-length CFTR protein. This RNA editing approach is based on the targeting of the deaminase domain of the hADAR2 enzyme fused to the dCas13b protein to a specific adenosine to be edited to inosine in the mutant mRNA. Targeting specificity is allowed by a guide RNA (gRNA) complementarily to the target region and recognized by the dCas13b protein. Here, we used the REPAIRv2 platform to edit the UGA PTC to UGG in different cell types, namely IB3-1 cells, HeLa, and FRT cells engineered to express H2BGFPopal and CFTRW1282X, respectively.

PMID: 32640650 [PubMed - in process]

Vav3 Mediates Pseudomonas aeruginosa Adhesion to the Cystic Fibrosis Airway Epithelium.

Cell Rep. 2020 Jul 07;32(1):107842

Authors: Badaoui M, Zoso A, Idris T, Bacchetta M, Simonin J, Lemeille S, Wehrle-Haller B, Chanson M

Abstract
Pseudomonas aeruginosa (Pa) represents the leading cause of airway infection in cystic fibrosis (CF). Early airways colonization can be explained by enhanced adhesion of Pa to the respiratory epithelium. RNA sequencing (RNA-seq) on fully differentiated primary cultures of airway epithelial cells from CF and non-CF donors predict that VAV3, β1 INTEGRIN, and FIBRONECTIN genes are significantly enriched in CF. Indeed, Vav3 is apically overexpressed in CF, associates with active β1 integrin luminally exposed, and increases fibronectin deposition. These luminal microdomains, rich in fibronectin and β1 integrin and regulated by Vav3, mediate the increased Pa adhesion to the CF epithelium. Interestingly, Vav3 inhibition normalizes the CF-dependent fibronectin and β1-integrin ectopic expression, improves the CF epithelial integrity, and prevents the enhanced Pa trapping to the CF epithelium. Through its capacity to promote a luminal complex with active β1 integrin and fibronectin that favors bacteria trapping, Vav3 may represent a new target in CF.

PMID: 32640241 [PubMed - as supplied by publisher]

Mucosal bacterial vaccines in clinical practice - a novel approach to an old problem?

Rev Assoc Med Bras (1992). 2020 May;66(5):659-665

Authors: Machado JN, Costa JC, Costa T, Rodrigues C

Abstract
OBJECTIVES To evaluate the efficacy of mucosal bacterial vaccines (MBV) in reducing the number of exacerbations in patients with chronic respiratory disease. METHODS A prospective cohort study of patients followed at the Pneumology Unit of the University and Hospital Centre of Coimbra, with frequent infectious exacerbations (3 or more) despite the best therapeutic strategies employed. MBV was used as additional therapy. The number of exacerbations 1 year before therapy and 1 year after it were analyzed. RESULTS A sample of 11 individuals, 45.5% male, mean age 62.5 years. Eight patients had non-cystic fibrosis bronchiectasis, 2 COPD (1 on long-term oxygen therapy), and 1 patient with Mounier Kuhn's syndrome. Three patients were on azithromycin, 1 on inhaled colistin, and 2 on inhaled tobramycin. Out of the 11 patients, one presented complication (fever), which led to a suspension of therapy (excluded from results). Of the 10 patients who completed treatment, 5 had bacterial colonization and were submitted to a custom vaccine. The remaining 6 completed the standard composition. The average of infectious exacerbations in the previous year was 4.3 (0.7 with hospitalization). In the year after therapy, the mean number was 1.5 (0.5 with hospitalization). CONCLUSION The results obtained in this study favor the use of bacterial immunostimulation to reduce the frequency of RRIs in patients with chronic respiratory disease.

PMID: 32638954 [PubMed - in process]

Pulmonary Aspergillosis: An Evolving Challenge for Diagnosis and Treatment.

Infect Dis Ther. 2020 Jul 07;:

Authors: Russo A, Tiseo G, Falcone M, Menichetti F

Abstract
Aspergillus is a mold that may lead to different clinical pictures, from allergic to invasive disease, depending on the patient's immune status and structural lung diseases. Chronic pulmonary aspergillosis is an infection with a locally invasive presentation, reported especially in patients with chronic pulmonary disease, while aspergilloma is typically found in patients with previously formed cavities in the lungs. Allergic bronchopulmonary aspergillosis is due to a hypersensitivity reaction to Aspergillus antigens and is more frequently described in patients with moderate-severe asthma or cystic fibrosis. Invasive pulmonary aspergillosis mainly occurs in patients with neutropenia or immunodeficiency, but has increasingly been recognized as an emerging disease of non-neutropenic patients. The significance of this infection has dramatically increased in recent years, considering the high number of patients with an impaired immune state associated with the management and treatment of neoplasm, solid or hematological transplantation, autoimmune diseases, and inflammatory conditions. Moreover, prolonged steroid treatment is recognized as an important risk factor, especially for invasive disease. In this setting, critically ill patients admitted to intensive care units and/or with chronic obstructive pulmonary disease could be at higher risk for invasive infection. This review provides an update on the clinical features and risk factors of pulmonary aspergillosis. Current approaches for the diagnosis, management, and treatment of these different forms of pulmonary aspergillosis are discussed.

PMID: 32638227 [PubMed - as supplied by publisher]

Long Term Non-invasive Ventilation in Children With Central Hypoventilation.

Front Pediatr. 2020;8:288

Authors: Paglietti MG, Esposito I, Goia M, Rizza E, Cutrera R, Bignamini E

Abstract
Central hypoventilation (CH) is a quite rare disorder caused by some congenital or acquired conditions. It is featured by increased arterial concentration of serum carbon dioxide related to an impairment of respiratory drive. Patients affected by CH need to be treated by mechanical ventilation in order to achieve appropriate ventilation and oxygenation both in sleep and wakefulness. In fact, in severe form of Congenital Central Hypoventilation Syndrome (CCHS) hypercarbia can be present even during the day. Positive pressure ventilation via tracheostomy is the first therapeutic option in this clinical condition, especially in congenital forms. Non-Invasive ventilation is a an option that must be reserved for more stable clinical situations and that requires careful monitoring over time.

PMID: 32637385 [PubMed]

Epithelial vectorial ion transport in cystic fibrosis: Dysfunction, measurement, and pharmacotherapy to target the primary deficit.

SAGE Open Med. 2020;8:2050312120933807

Authors: Clunes LA, McMillan-Castanares N, Mehta N, Mesadieu A, Rodriguez J, Maj M, Clunes MT

Abstract
Cystic fibrosis patients display multi-organ system dysfunction (e.g. pancreas, gastrointestinal tract, and lung) with pathogenesis linked to a failure of Cl- secretion from the epithelial surfaces of these organs. If unmanaged, organ dysfunction starts early and patients experience chronic respiratory infection with reduced lung function and a failure to thrive due to gastrointestinal malabsorption. Early mortality is typically caused by respiratory failure. In the past 40 years of newborn screening and improved disease management have driven the median survival up from the mid-teens to 43-53, with most of that improvement coming from earlier and more aggressive management of the symptoms. In the last decade, promising pharmacotherapies have been developed for the correction of the underlying epithelial dysfunction, namely, Cl- secretion. A new generation of systemic drugs target the mutated Cl- channels in cystic fibrosis patients and allow trafficking of the immature mutated protein to the cell membrane (correctors), restore function to the channel once in situ (potentiators), or increase protein levels in the cells (amplifiers). Restoration of channel function prior to symptom development has the potential to significantly change the trajectory of disease progression and their evidence suggests that a modest restoration of Cl- secretion may delay disease progression by decades. In this article, we review epithelial vectorial ion and fluid transport, its quantification and measurement as a marker for cystic fibrosis ion transport dysfunction, and highlight some of the recent therapies targeted at the dysfunctional ion transport of cystic fibrosis.

PMID: 32637102 [PubMed]

Parallel Analysis of Cystic Fibrosis Sputum and Saliva Reveals Overlapping Communities and an Opportunity for Sample Decontamination.

mSystems. 2020 Jul 07;5(4):

Authors: Lu J, Carmody LA, Opron K, Simon RH, Kalikin LM, Caverly LJ, LiPuma JJ

Abstract
Culture-independent studies of the cystic fibrosis (CF) airway microbiome typically rely on expectorated sputum to assess the microbial makeup of lower airways. These studies have revealed rich bacterial communities. There is often considerable overlap between taxa observed in sputum and those observed in saliva, raising questions about the reliability of expectorated sputum as a sample representing lower airway microbiota. These concerns prompted us to compare pairs of sputum and saliva samples from 10 persons with CF. Using 16S rRNA gene sequencing and droplet digital PCR (ddPCR), we analyzed 37 pairs of sputum and saliva samples, each collected from the same person on the same day. We developed an in silico postsequencing decontamination procedure to remove from sputum the fraction of DNA reads estimated to have been contributed by saliva during expectoration. We demonstrate that while there was often sizeable overlap in community membership between sample types, expectorated sputum typically contains a higher bacterial load and a less diverse community compared to saliva. The differences in diversity between sputum and saliva were more pronounced in advanced disease stage, owing to increased relative abundance of the dominant taxa in sputum. Our effort to model saliva contamination of sputum in silico revealed generally minor effects on community structure after removal of contaminating reads. Despite considerable overlap in taxa observed between expectorated sputum and saliva samples, the impact of saliva contamination on measures of lower airway bacterial community composition in CF using expectorated sputum appears to be minimal.IMPORTANCE Cystic fibrosis is an inherited disease characterized by chronic respiratory tract infection and progressive lung disease. Studies of cystic fibrosis lung microbiology often rely on expectorated sputum to reflect the microbiota present in the lower airways. Passage of sputum through the oropharynx during collection, however, contributes microbes present in saliva to the sample, which could confound interpretation of results. Using culture-independent DNA sequencing-based analyses, we characterized the bacterial communities in pairs of expectorated sputum and saliva samples to generate a model for "decontaminating" sputum in silico Our results demonstrate that salivary contamination of expectorated sputum does not have a large effect on most sputum samples and that observations of high bacterial diversity likely accurately reflect taxa present in cystic fibrosis lower airways.

PMID: 32636336 [PubMed]

Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline.

Eur Respir J. 2020 Jul;56(1):

Authors: Daley CL, Iaccarino JM, Lange C, Cambau E, Wallace RJ, Andrejak C, Böttger EC, Brozek J, Griffith DE, Guglielmetti L, Huitt GA, Knight SL, Leitman P, Marras TK, Olivier KN, Santin M, Stout JE, Tortoli E, van Ingen J, Wagner D, Winthrop KL

Abstract
Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM. A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases.

PMID: 32636299 [PubMed - in process]

Objective Measures of Vest Therapy Adherence Among Pediatric Subjects With Cystic Fibrosis.

Respir Care. 2020 Jul 07;:

Authors: Benoit CM, Christensen E, Nickel AJ, Shogren S, Johnson M, Thompson EF, McNamara J

Abstract
BACKGROUND: Airway clearance techniques (ACTs), including high-frequency chest wall oscillation (vest therapy), are important for maintaining lung function for patients with cystic fibrosis, but daily completion of ACTs is time-consuming and cumbersome. Patient adherence is a persistent challenge, and adherence data are largely patient reported, which may reduce accuracy. To provide definitive adherence data, this study utilized a Bluetooth-enabled vest therapy system to remotely collect objective adherence data from a cohort of pediatric subjects.
METHODS: Vest usage data were collected over a 12-month period and compared to each subject vest prescription. Because vest prescriptions are multifaceted, we developed metrics to examine adherence to the various facets (eg, daily treatment, treatments per day, treatment duration, frequency settings, and frequency and pressure settings combined) as well as an overall adherence metric.
RESULTS: Among the 73 enrolled subjects, 62 (50% male, age range 2-19 y) completed the study. Among adolescent subjects age 13-19 y, average adherence to daily vest therapy (44.0%) was significantly lower than that among subjects 0-6 y old (77.8%) and subjects 7-12 y old (89.5%). As more prescribed therapy components were combined into a single adherence metric, all age groups declined in mean adherence rates, with overall adherence a decreasing function of age.
CONCLUSIONS: Employing new technology to remotely collect vest usage data allows for a granular examination of vest therapy adherence. While maintaining high levels of treatment adherence becomes increasingly difficult as children age, we also found substantial reductions in adherence rates among all age groups when more complex aspects of therapy prescriptions, such as frequency and pressure settings, were examined. These data illustrate areas providers and care teams can focus on to improve patient adherence to vest prescriptions.

PMID: 32636276 [PubMed - as supplied by publisher]

Role of Curcumin and (-)-Epigallocatechin-3-O-Gallate in Bladder Cancer Treatment: A Review.

Cancers (Basel). 2020 Jul 05;12(7):

Authors: Piwowarczyk L, Stawny M, Mlynarczyk DT, Muszalska-Kolos I, Goslinski T, Jelińska A

Abstract
The incidence of bladder cancer (BC) is increasing, and although current therapeutic approaches are effective in many cases, recurrence of BC is common. Therefore, it seems necessary to search not only for novel therapeutic approaches, but also for new therapeutic agents. Natural polyphenols, such as curcumin (CUR) and epigallocatechin gallate (EGCG), possess remarkable antitumor activity. Their biochemical mechanisms of action include regulation of signaling pathways, modeling of proteins involved in apoptosis and cell cycle inhibition, angiogenesis, and the proliferation, migration and adhesion of tumor cells. Both compounds also present antioxidant, anti-inflammatory, antibacterial and antiviral properties. CUR has been considered a promising candidate for the treatment of cystic fibrosis, Alzheimer's disease or malaria, whereas EGCG can play a supportive role in the treatment of obesity, metabolic and neurodegenerative diseases. The review summarizes the latest research on the role of CUR and EGCG in the treatment of BC. In particular, the effects of CUR and EGCG, and their prospects for use in BC therapy, their inhibition of cancer development and their prevention of multidrug resistance, are described. The literature's data indicate the possibility of achieving the effect of synergism of both polyphenols in BC therapy, which has been observed so far in the treatment of ovarian, breast and prostate cancer.

PMID: 32635637 [PubMed]