Impact of CYP3A5 phenotype on tacrolimus concentrations after sublingual and oral administration in lung transplant.

Pharmacogenomics. 2019 Apr 15;:

Authors: Pasternak AL, Kidwell KM, Dempsey JM, Gersch CL, Pesch A, Sun Y, Rae JM, Hertz DL, Park JM

Abstract
AIM: This study evaluated the impact of CYP3A5 genotype and other patient characteristics on sublingual (SL) tacrolimus exposure and compared the relationship with oral administration.
PATIENTS & METHODS: Tacrolimus concentrations were retrospectively collected for adult lung transplant recipients, who were genotyped for CYP3A5*3, CYP3A4*22, CYP3A7*1C, and POR*28. Regression analyses were performed to determine covariates that impacted the SL and oral tacrolimus concentration/dose ratios.
RESULTS: An interaction of CYP3A5 genotype and CYP3A inhibitor increased the SL concentration/dose, while cystic fibrosis decreased the SL concentration/dose. The oral concentration/dose was independently associated with these covariates and was increased by serum creatinine and number of tacrolimus doses.
CONCLUSION: This study suggests personalized dosing strategies for tacrolimus likely need to consider characteristics beyond CYP3A5 genotype.

PMID: 30983501 [PubMed - as supplied by publisher]

[Chronic rhinosinusitis and cystic fibrosis in adult].

Rev Prat. 2019 Mar;69(3):279-280

Authors: Mortuaire G

PMID: 30983252 [PubMed - in process]

[Problems posed by genetic diseases, concerning: chromosomal disorders, trisomy 21; genetic diseases, cystic fibrosis, DNA instability disorders: fragile X syndrome].

Rev Prat. 2019 Feb;69(2):e47-e54

Authors: Yauy K, Geneviève D

PMID: 30983237 [PubMed - in process]

Effectiveness of ivacaftor in cystic fibrosis: Improvement of liver cirrhosis, nutritional status and respiratory function.

Med Clin (Barc). 2019 Apr 11;:

Authors: Martín de Vicente C, García Romero R

PMID: 30982531 [PubMed - as supplied by publisher]

A total pleural covering of absorbable cellulose mesh prevents pneumothorax recurrence in patients with Birt-Hogg-Dubé syndrome.

Orphanet J Rare Dis. 2018 05 15;13(1):78

Authors: Mizobuchi T, Kurihara M, Ebana H, Yamanaka S, Kataoka H, Okamoto S, Kobayashi E, Kumasaka T, Seyama K

Abstract
BACKGROUND: Birt-Hogg-Dubé syndrome (BHDS) is a recently recognized inherited multiple cystic lung disease causing recurrent pneumothoraces. Similarly to the lesions in patients with lymphangioleiomyomatosis (LAM), the pulmonary cysts are innumerable and widely dispersed and cannot all be removed. We recently described a total pleural covering (TPC) that covers the entire visceral pleura with oxidized regenerated cellulose (ORC) mesh. TPC successfully prevented the recurrence of pneumothorax in LAM patients. The purpose of this study was to evaluate the effect of an ORC pleural covering on pneumothorax recurrence in BHDS patients.
RESULTS: This retrospective study enrolled a total of 81 pneumothorax patients with the diagnosis of BHDS who underwent 90 covering surgeries from January 2010 to August 2017 at Tamagawa Hospital. During the first half of the study period, a lower pleural covering (LPC) which covered the affected area with ORC mesh was mainly used to treat 38 pneumothoraces. During the second half of the study period, TPC was primarily performed for 52 pneumothoraces. All the thoracoscopic surgeries were successfully performed without serious complications (≥ Clavien-Dindo grade III). The median follow-up periods after LPC/TPC were 66/34 months, respectively. Pneumothorax recurrence rates after LPC at 2.5/5/7.5 years postoperatively were 5.4/12/42%, respectively; none of the patients who had underwent TPC developed postoperative pneumothorax recurrence (P = 0.032).
CONCLUSIONS: TPC might be an effective option for surgical treatment of intractable pneumothorax in patients with BHDS.

PMID: 29764481 [PubMed - indexed for MEDLINE]

p.Phe508del, p.Gly542X, p.Arg1162X, p.Asn1303Lys, and p.Lys683serfsX38 mutations in CF newborn screening of Brazilian children.

Clin Genet. 2017 07;92(1):115-116

Authors: Ribas DIR, Escaliante CH, Bortoli CG, de Oliveira CRF, Mikami LR, Riedi CA, Raskin S, Rosário Filho NA, Pereira-Ferrari L

PMID: 28134438 [PubMed - indexed for MEDLINE]

Genistein antagonizes gliadin-induced CFTR malfunction in models of celiac disease.

Aging (Albany NY). 2019 Apr 12;:

Authors: Esposito S, Villella VR, Ferrari E, Monzani R, Tosco A, Rossin F, D'Eletto M, Castaldo A, Luciani A, Silano M, Bona G, Marseglia GL, Romani L, Piacentini M, Raia V, Kroemer G, Maiuri L

Abstract
In celiac disease (CD), an intolerance to dietary gluten/gliadin, antigenic gliadin peptides trigger an HLA-DQ2/DQ8-restricted adaptive Th1 immune response. Epithelial stress, induced by other non-antigenic gliadin peptides, is required for gliadin to become fully immunogenic. We found that cystic-fibrosis-transmembrane-conductance-regulator (CFTR) acts as membrane receptor for gliadin-derived peptide P31-43, as it binds to CFTR and impairs its channel function. P31-43-induced CFTR malfunction generates epithelial stress and intestinal inflammation. Maintaining CFTR in an active open conformation by the CFTR potentiators VX-770 (Ivacaftor) or Vrx-532, prevents P31-43 binding to CFTR and controls gliadin-induced manifestations. Here, we evaluated the possibility that the over-the-counter nutraceutical genistein, known to potentiate CFTR function, would allow to control gliadin-induced alterations. We demonstrated that pre-treatment with genistein prevented P31-43-induced CFTR malfunction and an epithelial stress response in Caco-2 cells. These effects were abrogated when the CFTR gene was knocked out by CRISP/Cas9 technology, indicating that genistein protects intestinal epithelial cells by potentiating CFTR function. Notably, genistein protected gliadin-sensitive mice from intestinal CFTR malfunction and gliadin-induced inflammation as it prevented gliadin-induced IFN-γ production by celiac peripheral-blood-mononuclear-cells (PBMC) cultured ex-vivo in the presence of P31-43-challenged Caco-2 cells. Our results indicate that natural compounds capable to increase CFTR channel gating might be used for the treatment of CD.

PMID: 30981209 [PubMed - as supplied by publisher]

AMPs as Anti-biofilm Agents for Human Therapy and Prophylaxis.

Adv Exp Med Biol. 2019;1117:257-279

Authors: Shahrour H, Ferrer-Espada R, Dandache I, Bárcena-Varela S, Sánchez-Gómez S, Chokr A, Martínez-de-Tejada G

Abstract
Microbial cells show a strong natural tendency to adhere to surfaces and to colonize them by forming complex communities called biofilms. In this growth mode, biofilm-forming cells encase themselves inside a dense matrix which efficiently protects them against antimicrobial agents and effectors of the immune system. Moreover, at the physiological level, biofilms contain a very heterogeneous cell population including metabolically inactive organisms and persisters, which are highly tolerant to antibiotics. The majority of human infectious diseases are caused by biofilm-forming microorganisms which are responsible for pathologies such as cystic fibrosis, infective endocarditis, pneumonia, wound infections, dental caries, infections of indwelling devices, etc. AMPs are well suited to combat biofilms because of their potent bactericidal activity of broad spectrum (including resting cells and persisters) and their ability to first penetrate and then to disorganize these structures. In addition, AMPs frequently synergize with antimicrobial compounds and were recently reported to repress the molecular pathways leading to biofilm formation. Finally, there is a very active research to develop AMP-containing coatings that can prevent biofilm formation by killing microbial cells on contact or by locally releasing their active principle. In this chapter we will describe these strategies and discuss the perspectives of the use of AMPs as anti-biofilm agents for human therapy and prophylaxis.

PMID: 30980362 [PubMed - in process]

[Other specific types of diabetes and exocrine pancreatic insufficiency (Update 2019)].

Wien Klin Wochenschr. 2019 Apr 12;:

Authors: Kaser S, Winhofer-Stöckl Y, Kazemi-Shirazi L, Hofer SE, Brath H, Sourij H, Vila G, Abrahamian H, Riedl M, Weitgasser R, Resl M, Clodi M, Luger A

Abstract
The heterogenous catagory "specific types of diabetes due to other causes" encompasses disturbances in glucose metabolism due to other endocrine disorders such as acromegaly or hypercortisolism, drug-induced diabetes (e. g. antipsychotic medications, glucocorticoids, immunosuppressive agents, highly active antiretroviral therapy (HAART)), genetic forms of diabetes (e. g. Maturity Onset Diabetes of the Young (MODY), neonatal diabetes, Down Syndrome, Klinefelter Syndrome, Turner Syndrome), pancreatogenic diabetes (e. g. postoperatively, pancreatitis, pancreatic cancer, haemochromatosis, cystic fibrosis), and some rare autoimmune or infectious forms of diabetes. Diagnosis of specific diabetes types might influence therapeutic considerations. Exocrine pancreatic insufficiency is not only found in patients with pancreatogenic diabetes but is also frequently seen in type 1 and long-standing type 2 diabetes.

PMID: 30980164 [PubMed - as supplied by publisher]

Integrated transcriptomic and proteomic analysis of human eccrine sweat glands identifies missing and novel proteins.

Mol Cell Proteomics. 2019 Apr 12;:

Authors: Na CH, Sharma N, Madugundu AK, Chen R, Atalar Aksit M, Rosson GD, Cutting GR, Pandey A

Abstract
The eccrine sweat gland is an exocrine gland that is involved in the secretion of sweat for control of temperature. Malfunction of the sweat glands can result in disorders such as miliaria, hyperhidrosis and bromhidrosis. Understanding the transcriptome and proteome of sweat glands is important for understanding their physiology and role in diseases. However, no systematic transcriptome or proteome analysis of sweat glands has yet been reported. Here, we isolated eccrine sweat glands from human skin by microdissection and performed RNA-seq and proteome analysis. In total, ~138,000 transcripts and ~6,100 proteins were identified. Comparison of the RNA-seq data of eccrine sweat glands to other human tissues revealed the closest resemblance to the cortex region of kidneys. The proteome data showed enrichment of proteins involved in secretion, reabsorption, and wound healing. Importantly, protein level identification of the calcium ion channel TRPV4 suggests the importance of eccrine sweat glands in re-epithelialization of wounds and prevention of dehydration. We also identified 2 previously missing proteins from our analysis. Using a proteogenomic approach, we identified 7 peptides from 5 novel genes, which we validated using synthetic peptides. Most of the novel proteins were from short open reading frames (sORFs) suggesting that many sORFs still remain to be annotated in the human genome. This study presents the first integrated analysis of the transcriptome and proteome of the human eccrine sweat gland and would become a valuable resource for studying sweat glands in physiology and disease.

PMID: 30979791 [PubMed - as supplied by publisher]

Cystic fibrosis dyslipidaemia: A cross-sectional study.

J Cyst Fibros. 2019 Apr 09;:

Authors: Nowak JK, Szczepanik M, Wojsyk-Banaszak I, Mądry E, Wykrętowicz A, Krzyżanowska-Jankowska P, Drzymała-Czyż S, Nowicka A, Pogorzelski A, Sapiejka E, Skorupa W, Miśkiewicz-Chotnicka A, Lisowska A, Walkowiak J

Abstract
BACKGROUND: The interest in cystic fibrosis (CF) dyslipidaemia as a potential risk factor for cardiovascular disease is increasing with patients' survival. This study aimed to investigate CF dyslipidaemia, its clinical correlates and links to oxidized low-density lipoprotein (oxLDL), adiponectin, and apolipoprotein E (APOE).
METHODS: This cross-sectional study assessed clinical characteristics of CF, as well as the serum lipid profile, oxLDL, adiponectin, and APOE.
RESULTS: In total, 108 CF subjects were enrolled in this study, with a median age of 22 years, BMI of 20.5 kg/m2, FEV1% of 61%, of which 81% were pancreatic insufficient (PI). Healthy subjects (HS; n = 51) were in similar age. Hypocholesterolaemia occurred in 31% of CF subjects and in no HS. Hypertriglyceridaemia concerned 21% of patients (HS: 8%, p = .04), and low HDL-C 45% (HS: 6%, p < .0001). At least one of these three CF dyslipidaemia disturbances was present in 62% of CF subjects, but there were no significant differences in oxLDL, oxLDL/LDL-C ratio, adiponectin, and APOE between CF and HS groups. PI was independently associated with low total cholesterol, LDL-C, and non-high density lipoprotein cholesterol, with age and sex also modifying lipid levels. In CF (n = 42), triglycerides did not correlate with serum tumour necrosis factor α (TNF-α).
CONCLUSIONS: CF dyslipidaemia is highly prevalent and heterogenous. The lipid profile weakly associates with the clinical characteristics of CF as well as oxLDL, adiponectin, and APOE. Further research is needed, especially regarding HDL function in CF, the causes of hypertriglyceridaemia, and the value of essential fatty acid supplementation for CF dyslipidaemia.

PMID: 30979683 [PubMed - as supplied by publisher]

Unusual Cystic Fibrosis Transmembrane Conductance Regulator Mutations and Liver Disease: A Case Series and Review of the Literature.

Transplant Proc. 2019 Apr;51(3):790-793

Authors: Khan HH, Mew NA, Kaufman SS, Yazigi NA, Fishbein TM, Khan KM

Abstract
Cystic fibrosis (CF) is caused by a mutation in the CF transmembrane conductance regulator (CFTR) gene, deranging the activity of chloride channels on the epithelial cell surface. Herein we describe end-stage liver disease in 3 infants with rare CFTR gene mutations; 2 of them were heterozygous. Case 1 was a premature male infant with negative CF screening at birth who developed a small bowel obstruction in the neonatal period requiring an ileostomy, with subsequent cholestatic liver disease and portal hypertension. In addition, he was noted to have frequent respiratory infections prompting a sweat test, which was positive. Genetic testing revealed that he was heterozygous for P.1177F. He then underwent a successful liver transplant. Case 2 was a female infant who developed progressive cholestasis with poor weight gain and was found to have neonatal hepatitis on liver biopsy. A sweat test was negative and genetic testing revealed she was heterozygous for CFTR and PEX26 gene mutations. She subsequently developed pneumatosis involving the cecum that was treated conservatively, followed by a successful liver transplant. Case 3 was a male infant who developed progressive liver disease, with liver biopsy showing neonatal hepatitis. He was extensively investigated but had a negative sweat test on repeated studies. Genetic testing revealed that the patient was heterozygous P.K186N-variant in the AKRID1 gene and homozygous P.R75Q-variant in the CFTR gene. Unfortunately, he succumbed to an acute upper gastrointestinal hemorrhage. Rare and unusual CFTR mutations, even in the heterozygous form, may be a feature in otherwise undiagnosed end-stage liver disease of infancy.

PMID: 30979466 [PubMed - in process]

Can Nebulised Colistin Therapy Improve Outcomes in Critically Ill Children with Multi-Drug Resistant Gram-Negative Bacterial Pneumonia?

Antibiotics (Basel). 2019 Apr 11;8(2):

Authors: Aygun F, Aygun FD, Varol F, Durak C, Cokugraş H, Camcioglu Y, Cam H

Abstract
In the past decade, multidrug-resistant (MDR) gram-negative bacteria have become a major problem, especially for patients in intensive care units. Recently, colistin became the last resort therapy for MDR gram-negative bacteria infections. However, nebulised colistin use was limited to adult patients. Thus, we investigated the efficacy and safety of nebulised colistin treatment against MDR microorganisms in the paediatric intensive care unit (PICU). Data of all patients admitted for various critical illnesses (January 2016 to January 2019) were reviewed. Differences between groups (with and without a history of nebulised colistin) were compared. Of 330 patients, 23 (6.97%) used nebulised colistin. Significant relationships were found between nebulised colistin usage and several prognostic factors (inotropic drug use (p = 0.009), non-invasive mechanical ventilation (p ≤ 0.001), duration in PICU (p ≤ 0.001), and C-reactive protein level (p = 0.003)). The most common microorganism in tracheal aspirate and sputum cultures was Pseudomonas aeruginosa (13 patients). The most common underlying diagnosis was cystic fibrosis, noted in 6 patients. No serious nephrotoxicity and neurotoxicity occurred. This study showed that colistin can be safely used directly in the airway of critically ill children. However, nebulised colistin use did not have a positive effect on mortality and prognosis.

PMID: 30979085 [PubMed]

Results from an online survey of adults with cystic fibrosis: Accessing and using life expectancy information.

PLoS One. 2019;14(4):e0213639

Authors: Keogh RH, Bilton D, Cosgriff R, Kavanagh D, Rayner O, Sedgwick PM

Abstract
Cystic fibrosis (CF) is the one of the most common inherited diseases. It affects around 10,000 people in the UK, and the median survival age is 47. Recent developments making use of longitudinal patient registry data are producing more detailed and relevant information about predicted life expectancy in CF based on current age and clinical measurements. The objective of this study was toconduct an online survey of adults with CF living in the UK using a web-based questionnaire to investigate: (i) if and how they access information on life expectancy; (ii) what they use it for; (iii) if they want more personalised information on life expectancy or the time until other milestones. The survey was advertised through the Cystic Fibrosis Trust using social media. There were 85 respondents, covering men (39%) and women (61%) aged 16-65. 75% had received information on life expectancy either from their CF care team (34%) or other sources (71%), the most common being the Cystic Fibrosis Trust website and research literature. Most people who received information found it to be beneficial and reported using it in a variety of ways, including to plan strategies for maintaining as best health as possible and to psychologically manage current health status. 82% of respondents were interested in more personalised information about their life expectancy, and participants also noted interest in other outcomes, including time to needing transplant or reaching a low level of lung function. Themes arising in text responses included the importance of good communication of information, the difficulty of relating general information to one's own circumstances, and a desire for increased information on factors that impact on survival in CF. As an outcome from this work, research is underway to establish how information on life expectancy can be presented to people with CF in an accessible way.

PMID: 30978192 [PubMed - in process]

Signalling Effects Induced by Acid Ceramidase in Human Epithelial Or Leukemic Cell Lines.

Cell Physiol Biochem. 2019;52(5):1092-1102

Authors: Baduva K, Büchter L, Kreyenkamp K, Westphal L, Wilker B, Kohnen M, Schuchman EH, Edwards MJ, Becker KA, Gulbins E, Carpinteiro A

Abstract
BACKGROUND/AIMS: Recent studies indicated that an inhalation treatment of cystic fibrosis mice with acid ceramidase prevents and eliminates infections with Pseudomonas aeruginosa and Stapyhlococcus aureus. Inhalation of acid ceramidase facilitated the elimination of P. aeruginosa in acutely- or chronically-infected mice with cystic fibrosis. Thus, inhalation of acid ceramidase might be a preventive and/or curative treatment for patients with cystic fibrosis suffering from pneumonia.
METHODS: We treated cultured epithelial cells or leukemic T-lymphocytes (Jurkat cells) with purified acid ceramidase and determined intracellular signalling events, proliferation and cell survival. Specifically, we measured the activity of AKT, p38-kinase and p70S6-kinase using activation-specific phospho-antibodies in western blot studies. Trypan Blue staining served to analyze proliferation and cell survival.
RESULTS: Our studies indicate that treatment of Chang epithelial cells or Jurkat T lymphocytes with purified acid ceramidase results in a dose dependent activation of AKT, p38-kinase and p70S6-kinase, while tyrosine phosphorylation of intracellular proteins remains largely unchanged. Acid ceramidase treatment did not change expression of tight junction proteins such as ZO-1, ZO-2 and occludin. Cellular viability and proliferation were not affected by acid ceramidase treatment.
CONCLUSION: Our data suggest that treatment of epithelial cells and lymphocytes with acid ceramidase results in activation of distinct pathways, in particular AKT- and p38K-dependent pathways, while no global activation or cell death was observed.

PMID: 30977990 [PubMed - in process]

lptG contributes to changes in membrane permeability and the emergence of multidrug hypersusceptibility in a cystic fibrosis isolate of Pseudomonas aeruginosa.

Microbiologyopen. 2019 Apr 12;:e844

Authors: Harrison LB, Fowler RC, Abdalhamid B, Selmecki A, Hanson ND

Abstract
PURPOSE: In the lungs of cystic fibrosis patients, Pseudomonas aeruginosa is exposed to a myriad of antibiotics leading to alterations in antibiotic susceptibility. This study identifies mutations resulting in hypersusceptibility in isogenic mutants of a P. aeruginosa clinical isolate, PA34.
METHODS: PA34 was exposed to subinhibitory concentrations of doripenem or meropenem during growth to mid-log phase. Antibiotic susceptibility of surviving colonies was determined by agar dilution. Two carbapenem-resistant colonies hypersusceptible to non-carbapenem antibiotics were selected for further analysis. Antibiotic resistance gene expression was evaluated by RT-rtPCR and OprD production by SDS-PAGE. PA34 and isogenic mutants were evaluated with whole genome sequencing. Sequence variants were confirmed by Sanger sequencing, and cognate genes in eight carbapenem-resistant clinical isolates hypersusceptible to non-carbapenem antibiotics were sequenced. Lipopolysaccharide preparations of PA34 and hypersusceptible mutants were evaluated with ProQ-Emerald stain.
RESULTS: Isogenic mutants showed 4- to 8-fold MIC increase for imipenem, meropenem, and doripenem. However, they were hypersusceptible (≥4-fold MIC decrease) to aminoglycosides, fluoroquinolones, and non-carbapenem β-lactams. Expression of ampC or mex-opr efflux pumps was unchanged, but OprD production was decreased. Mutations causing Q86H AlgU and G77C LptG amino acid substitutions and nonsense mutations within OprD were observed in both mutants. Lipopolysaccharide modifications were observed between isogenic mutants and PA34. Non-synonymous mutations in LptF or LptG were observed in 6/8 hypersusceptible clinical isolates resistant to carbapenem antibiotics.
CONCLUSION: Evaluation of hypersusceptible mutants identified the association between lptG and a hypersusceptible phenotype. Modifications in lipopolysaccharide profiles suggests LptG modification interferes with lipopolysaccharide transport and contributes to hypersusceptibility.

PMID: 30977288 [PubMed - as supplied by publisher]

Transcytosis maintains CFTR apical polarity in the face of constitutive and mutation-induced basolateral missorting.

J Cell Sci. 2019 Apr 11;:

Authors: Bidaud-Meynard A, Bossard F, Schnúr A, Fukuda R, Veit G, Xu H, Lukacs GL

Abstract
Apical polarity of cystic fibrosis transmembrane conductance regulator (CFTR) is essential for solute and water transport in secretory epithelia and can be impaired in human diseases. Maintenance of apical polarity in the face of CFTR non-polarized delivery and inefficient apical retention of mutant CFTRs lacking PDZ-domain protein (NHERF1) interaction, remains enigmatic. Here we show that basolateral CFTR delivery originates from biosynthetic (∼35%) and endocytic (∼65%) recycling missorting. Basolateral channels are retrieved via basolateral-to-apical transcytosis, enhancing CFTR apical expression by two-fold and suppressing its degradation. CFTR transcytosis is microtubule-dependent but independent of Myo5B-, Rab11- and NHERF1 binding to its C-terminal DTRL motif in airway epithelia. Increased basolateral delivery due to compromised apical recycling and accelerated internalization upon impaired NHERF1-CFTR association is largely counterbalanced by CFTR efficient basolateral internalization and apical transcytosis. Thus, transcytosis represents a previously unrecognized but indispensable mechanism for maintaining CFTR apical polarity by attenuating its constitutive and mutation-induced basolateral missorting.

PMID: 30975917 [PubMed - as supplied by publisher]

Reply - Cystic fibrosis complicated by cor pulmonale: The first case report in Taiwan.

Pediatr Neonatol. 2019 Mar 26;:

Authors: Shyur SD

PMID: 30975616 [PubMed - as supplied by publisher]

Cystic fibrosis complicated by cor pulmonale: The first case report in Taiwan.

Pediatr Neonatol. 2019 Mar 26;:

Authors: Moslehi MA

PMID: 30975615 [PubMed - as supplied by publisher]

"Fortunate are those who take the first steps"? The psychosocial impact of novel drug development.

Paediatr Respir Rev. 2019 Feb 27;:

Authors: Dobra R, Madge S, Martin I, Weldon P, Simmonds N, Davies JC

Abstract
Novel drug development offers people with cystic fibrosis exciting opportunities but is not without challenges. Currently, there is an understandable emphasis on protecting patients' physical health when developing treatments. However, there appears to be little consideration of how novel drug development impacts on psychosocial wellbeing, or the downstream consequences of this. Using an illustrative case and reviewing the literature we explore themes regarding the psychosocial impact of trial participation and novel drug development and identify areas requiring further research. Through this, we hope to prepare healthcare professionals to better understand the needs of their patients in this rapidly evolving landscape.

PMID: 30975518 [PubMed - as supplied by publisher]