Funding Opportunity RFA-HL-18-010 from the NIH Guide for Grants and Contracts. The purpose of this Funding Opportunity Announcement (FOA) is to encourage innovative molecular and physiological research that could lead to early diagnosis or effective medical therapy for calcific aortic valve disease (CAVD). Applications from investigators in related fields (for example, mineralization and bone physiology, extracellular matrix physiology, and molecular imaging) are strongly encouraged.

Funding Opportunity RFA-AT-18-001 from the NIH Guide for Grants and Contracts. The purpose of this FOA is to solicit applications to examine the impact of behavioral interventions within the context of states plans for use of the SAMHSA Opioid STR grant funds authorized under the 21st Century Cures Act. Applications are encouraged for studies that examine the impact of interventions such as mindfulness meditation, cognitive behavioral therapy, or multi-disciplinary rehabilitation for primary or secondary prevention for opioid use disorder (OUD) or as an adjunct to medication assisted treatment (MAT) of OUD. Applications that emphasize treatment of the comorbidity of OUD and chronic pain are of particular interest.

Funding Opportunity RFA-HL-18-009 from the NIH Guide for Grants and Contracts. The purpose of this FOA is to provide access to a consultative resource for planning activities for late phase (phase II and beyond) single-site or multi-site investigator-initiated clinical trials that address critical clinical questions within the mission of the National Heart, Lung, and Blood Institute (NHLBI) and that require non-traditional clinical trial designs with the opportunity for statistical novelty and/or innovation. The FOA will support the development of feasible and well-designed clinical trials utilizing consultative services provided by the Innovative Clinical Trials Resource (ICTR) (N01).

Funding Opportunity RFA-HL-18-008 from the NIH Guide for Grants and Contracts. The purpose of this FOA is to provide support for planning activities for late phase (phase II and beyond) single-site or multi-site investigator-initiated clinical trials that address critical clinical questions within the mission of the National Heart, Lung, and Blood Institute (NHLBI) and that require non-traditional clinical trial designs with the opportunity for statistical novelty and/or innovation. The FOA will support the development of feasible and well-designed clinical trials utilizing consultative services provided by the Innovative Clinical Trials Resource (ICTR) (N01).

Related Articles

Fibrodysplasia ossificans progressiva. A case report and focus on the BMP signaling pathway.

Morphologie. 2016 Dec;100(331):250-255

Authors: Bouvard B, Masson C, Legrand E, Audran M

Abstract
Fibrodysplasia ossificans progressiva is a very rare heritable disease characterized by a progressive heterotopic endochondal ossification, occurring in the first decade of life, and leading thereafter to a severe ankylosis of the spine, limbs and jaw, with a progressive and severe functional disability. To date the cause of the disease remains unknown and no medical treatment has been proved efficient. It has recently been shown that a recurrent mutation in activation domain of the activin-receptor IA (ACVR1), a BMP receptor, could lead to an abnormal signalling pathway of BMP-4 and contribute to the occurrence of the devastating lesions characteristic of the disease.

PMID: 26948676 [PubMed - indexed for MEDLINE]

Simultaneous determination of selective serotonin reuptake inhibitors and their main metabolites in human breast milk by liquid chromatography-electrospray mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Apr 27;1057:101-109

Authors: Weisskopf E, Panchaud A, Nguyen KA, Grosjean D, Hascoët JM, Csajka C, Eap CB, Ansermot N, collaborators of the SSRI-Breast Milk study

Abstract
A bioanalytical method by high performance liquid chromatography coupled to electrospray mass spectrometry (HPLC-ESI-MS), adapted from a previously published method in plasma, was validated in breast milk for the simultaneous quantification of all antidepressants belonging to the class of selective serotonin reuptake inhibitors (citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline) and their major metabolites (desmethylcitalopram and norfluoxetine). Milk samples (250μl) first underwent protein precipitation followed by solid-phase extraction on a reversed phase/cation exchange sorbent. Analytes were thereafter separated on a XBridge C18 column (2.1mm×100mm; 3.5μm) using a mobile phase composed of ammonium acetate buffer (pH 8.1; 50mM) and acetonitrile in gradient mode. Detection was performed by a single quadrupole mass spectrometer running in selected ion monitoring in positive ionization mode. Method validation covered a wide concentration range of 2-500ng/ml for citalopram, desmethylcitalopram and paroxetine, 5-500ng/ml for sertraline, and 2-1000ng/ml for fluoxetine, norfluoxetine and fluvoxamine. Validation performances such as trueness (90.3-111.6%), repeatability (0.8-9.3%) and intermediate precision (0.9-9.5%) were in agreement with criteria from international guidelines and matrix effects for the analyte/internal standard ratios ranged from 92% to 110% (relative standard deviation <15%). Accuracy profiles (total error of trueness and precision) were lying within the limits of ±30% accepted in bioanalysis. Finally, the method was successfully applied to patient samples collected in a clinical pharmacokinetic study of nursing mothers taking an antidepressant treatment.

PMID: 28511118 [PubMed - as supplied by publisher]

Risk factors of allopurinol-induced severe cutaneous adverse reactions in a Thai population.

Pharmacogenet Genomics. 2017 May 15;:

Authors: Saksit N, Tassaneeyakul W, Nakkam N, Konyoung P, Khunarkornsiri U, Chumworathayi P, Sukasem C, Suttisai S, Piriyachananusorn N, Tiwong P, Chaiyakunapruk N, Sawanyawisuth K, Rerkpattanapipat T, Tassaneeyakul W

Abstract
BACKGROUND: Allopurinol is one of the most common causes of severe cutaneous adverse drug reactions (SCARs) including drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). This study identified the risk factors associated with the development of allopurinol-induced SCARs in a Thai population.
PATIENTS AND METHODS: Eighty-six allopurinol-induced SCARs (i.e. 19 DRESS and 67 SJS/TEN) and 182 allopurinol-tolerant patients were enrolled in the study. The HLA-B*58:01 allele was determined. Clinical and medicinal data were collected.
RESULTS: Results from multivariate analysis showed that only the HLA-B*58:01 and female sex were identified as risk factors of allopurinol-induced SCARs in this Thai population. Patients who carried the HLA-B*58:01 allele were at a higher risk of allopurinol-induced DRESS [odds ratio (OR)=149.2, 95% confidence interval (CI)=24.0-∞, P<1.00×10]. Similar results were observed in allopurinol-induced SJS/TEN (OR=175.0, 95% CI=44.3-690.9, P=1.69×10). The risk of allopurinol-induced SCARs in women was higher than that in men (OR=4.6, 95% CI=1.4-15.6, P=1.44×10). The overall mortality rate of allopurinol-induced SCARs was 11.39% and a higher mortality rate was observed in elderly women.
CONCLUSION: Among the risk factors identified, the HLA-B*58:01 allele had the greatest impact on the development of both phenotypes of allopurinol-induced SCARs in this studied Thai population. In case HLA-B*58:01 genotyping cannot be accessed, close monitoring of allopurinol usage, especially in elderly women with impaired renal function, is necessary to reduce the mortality rate of these life-threatening SCARs.

PMID: 28509689 [PubMed - as supplied by publisher]

The Importance of Gene-Drug-Drug-Interactions in Pharmacogenomics Decision Support: An Analysis Based on Austrian Claims Data.

Stud Health Technol Inform. 2017;236:121-127

Authors: Blagec K, Kuch W, Samwald M

Abstract
While pharmacogenomic testing combined with clinical decision support has the potential to increase the safety and efficacy of medical treatments, the intake of multiple prescription drugs can - if not sufficiently addressed by decision support solutions - impair the effectiveness of such interventions by modulating the capacity of precisely those enzymes whose function pharmacogenomic tests try to predict. We quantified the potential extent of such drug-mediated mismatches between genotype-derived phenotypes and real phenotypes, commonly called "phenoconversion", by screening claims data from 1,587,829 Austrian health insurance holders of the years 2006 and 2007 for concomitant prescriptions of drugs that can be dosed based on pharmacogenomics, and drugs that modulate enzyme activity. In total, 232,398 such prescription overlaps were detected, of which more than half (54.6%) could be attributed to co-prescriptions of moderate or strong modulators. Our results indicate that prescription drug-mediated phenoconversion is not uncommon, and should therefore be adequately reflected in decision support solutions by integrating algorithms to detect potential gene-drug-drug interactions.

PMID: 28508787 [PubMed - in process]

Supporting Molecular Tumor Boards in Molecular-Guided Decision-Making - The Current Status of Five German University Hospitals.

Stud Health Technol Inform. 2017;236:48-54

Authors: Hinderer M, Boerries M, Haller F, Wagner S, Sollfrank S, Acker T, Prokosch HU, Christoph J

Abstract
BACKGROUND: German university hospitals have started to establish molecular tumor boards in order to enable physicians to make molecular-guided decisions.
OBJECTIVE: Our aim was to describe the organizational structure and procedures which are currently supporting the molecular tumor boards of five German university hospitals.
METHODS: We conducted semi-structured interviews with experts of five university hospitals between December 2016 and February 2017.
RESULTS: We observed heterogeneity in both the organization of genetic testing and the management of the molecular tumor boards among the five hospitals. They used free-text documents in most of their support procedures rather than machine-readable documents.
CONCLUSION: There are three potentialities to support the process from genetic testing to reporting within the molecular tumor boards: (i) standardized pipeline to integrate automated variant calling and annotation; (ii) tools supporting the experts in creating their reports and presentations and (iii) implementing pharmacogenomic CDSS into clinical routine.

PMID: 28508778 [PubMed - in process]

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Brain-Derived Neurotrophic Factor Val66Met Gene Polymorphism Impacts on Migraine Susceptibility: A Meta-analysis of Case-Control Studies.

Front Neurol. 2017;8:159

Authors: Terrazzino S, Cargnin S, Viana M, Sances G, Tassorelli C

Abstract
Inconclusive results have been reported in studies investigating the association between the brain-derived neurotrophic factor (BDNF) rs6265 polymorphism and migraine. In the present study, we conducted a systematic review and meta-analysis on the published data in order to quantitatively estimate the relationship between rs6265 and migraine susceptibility. A comprehensive search was performed through PubMed, Web of Knowledge, and Cochrane databases up to October 2016. The pooled odds ratio (OR) with the corresponding 95% confidence interval (CI) was calculated to estimate the strength of the association with rs6265 under an additive, dominant, or recessive model of inheritance. A total of five studies including 1,442 cases and 1,880 controls were identified for the meta-analysis. The pooled data showed an increased risk of migraine for the allelic (OR: 1.17, 95% CI: 1.03-1.34, p = 0.014) or the dominant model of rs6265 (OR: 1.22, 95% CI: 1.05-1.41, p = 0.011). Statistical significance of rs6265 was lost when one single study was excluded from the analysis (dominant OR: 1.17, 95% CI: 1.00-1.38, p = 0.054; allelic OR: 1.14, 95% CI: 0.99-1.31, p = 0.067), suggesting lack of robustness of pooled estimates. When stratified by migraine type, a similar trend of association was detected with both MA and MO, but a statistically significant association of rs6265 was reached only with the MA subtype in the dominant model (OR: 1.22, 95% CI: 1.00-1.47, p = 0.047). The present meta-analysis supports that BDNF rs6265 may act as a genetic susceptibility factor for migraine. Nevertheless, large-scale studies are required to confirm our findings and to assess potential modifiers of the relationship between rs6265 and migraine.

PMID: 28507530 [PubMed - in process]

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Thiopurine S-methyltransferase polymorphisms in acute lymphoblastic leukemia, inflammatory bowel disease and autoimmune disorders: influence on treatment response.

Pharmgenomics Pers Med. 2017;10:143-156

Authors: Abaji R, Krajinovic M

Abstract
The thiopurine S-methyltransferase (TPMT) gene encodes for the TPMT enzyme that plays a crucial role in the metabolism of thiopurine drugs. Genetic polymorphisms in this gene can affect the activity of the TPMT enzyme and have been correlated with variability in response to treatment with thiopurines. Advances in the pharmacogenetics of TPMT allowed the development of dosing recommendations and treatment strategies to optimize and individualize prescribing thiopurine in an attempt to enhance treatment efficacy while minimizing toxicity. The influence of genetic polymorphisms in the TPMT gene on clinical outcome has been well-documented and replicated in many studies. In this review, we provide an overview of the evolution, results, conclusions and recommendations of selected studies that investigated the influence of TPMT pharmacogenetics on thiopurine treatment in acute lymphoblastic leukemia, inflammatory bowel disease and autoimmune disorders. We focus mainly on prospective studies that explored the impact of individualized TPMT-based dosing of thiopurines on clinical response. Together, these studies demonstrate the importance of preemptive TPMT genetic screening and subsequent dose adjustment in mitigating the toxicity associated with thiopurine treatment while maintaining treatment efficacy and favorable long-term outcomes. In addition, we briefly address the cost-effectiveness of this pharmacogenetics approach and its impact on clinical practice as well as the importance of recent breakthrough advances in sequencing and genotyping techniques in refining the TPMT genetic screening process.

PMID: 28507448 [PubMed - in process]

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Non-maturational covariates for dynamic systems pharmacology models in neonates, infants, and children: Filling the gaps beyond developmental pharmacology.

Eur J Pharm Sci. 2017 May 12;:

Authors: Allegaert K, Simons SHP, Tibboel D, Krekels E, Knibbe C, van den Anker J

Abstract
Pharmacokinetics and -dynamics show important changes throughout childhood. Studies on the different maturational processes that influence developmental pharmacology have been used to create population PK/PD models that can yield individualized pediatric drug dosages. These models were subsequently translated to semi-physiologically or physiology-based PK (PBPK) models that support predictions in pediatric patient cohorts and other special populations. Although these translational efforts are crucial, these models should be further improved towards individual patient predictions by including knowledge on non-maturational covariates. These efforts are needed to ultimately get to systems pharmacology models for children. These models take developmental changes relating to the pediatric dynamical system into account but also other aspects that may be of importance such as abnormal body composition, pharmacogenetics, critical illness and inflammatory status.

PMID: 28506866 [PubMed - as supplied by publisher]

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Antibiotics-induced gut microbiota dysbiosis promotes tumor initiation via affecting APC-Th1 development in mice.

Biochem Biophys Res Commun. 2017 May 12;:

Authors: Xu C, Ruan B, Jiang Y, Xue T, Wang Z, Lu H, Wei M, Wang S, Ye Z, Zhai D, Wang L, Lu Z

Abstract
Gut microbiota is critical for maintaining body immune homeostasis and thus affects tumor growth and therapeutic efficiency. Here, we investigated the link between microbiota and tumorgenesis in a mice model of subcutaneous melanoma cell transplantation, and explored the underlying mechanism. We found disruption of gut microbiota by pretreating mice with antibiotics promote tumor growth and remodeling the immune compartment within the primary tumor. Indeed, gut microbial dysbiosis reduced the infiltrated mature antigen-presenting cells of tumor, together with lower levels of co-stimulators, such as CD80, CD86 and MHCII, as well as defective Th1 cytokines, including IFNγ, TNFα, IL12p40, and IL12p35. Meantime, splenic APCs displayed blunted ability in triggering T cell proliferation and IFNγ secretion. However, oral administration of LPS restored the immune surveillance effects and thus inhibited tumor growth in the antibiotics induced gut microbiota dysbiosis group. Taken together, these data highly supported that antibiotics induced gut microbiota dysbiosis promotes tumor initiation, while LPS supplementation would restore the effective immune surveillance and repress tumor initiation.

PMID: 28506830 [PubMed - as supplied by publisher]

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Variants of the ADRB2 Gene in COPD: Systematic Review and Meta-Analyses of Disease Risk and Treatment Response.

COPD. 2017 May 16;:1-10

Authors: Nielsen AO, Jensen CS, Arredouani MS, Dahl R, Dahl M

Abstract
The β2-adrenergic receptor (ADRB2) is an important regulator of airway smooth muscle tone in chronic obstructive pulmonary disease (COPD). Variants that impair ADRB2 function could increase disease risk or reduce the response to endogenous and inhaled adrenergic agonists in COPD. We performed a systematic review and three meta-analyses to assess whether three functional variants (Thr164Ile, Arg16Gly, and Gln27Glu) in the ADRB2 gene are associated with elevated risk of disease or reduced therapeutic response to inhaled β2-agonists in COPD. We searched the medical literature from 1966 to 2017 and found 16 relevant studies comprising 85381 study subjects. The meta-analyses found no significant association between ADRB2 genotype and COPD risk. The summary odds ratios (ORs) for COPD in Thr164Ile homozygotes and heterozygotes were 2.57 (95% confidence interval (CI): 0.54-12.4) and 1.17 (95% CI: 0.96-1.44), respectively. Corresponding summary ORs for COPD in Arg16Gly homozygotes and heterozygotes were 0.97 (95% CI: 0.76-1.22) and 1.01 (95% CI: 0.81-1.26), while summary ORs for COPD in Gln27Glu homozygotes and heterozygotes were 1.00 (95% CI: 0.80-1.25) and 0.94 (95% CI: 0.69-1.24), respectively. When stratified by ethnicity, the summary ORs for COPD did not differ from 1.0 for any of the ADRB2 variants among Asian, Caucasian, or African populations. We found no consistent associations between ADRB2 genotype and treatment response to inhaled β2-agonists in COPD. This systematic review and meta-analyses found that COPD risk and response to inhaled β2-agonists were not associated with Thr164Ile, Arg16Gly, and Gln27Glu genotypes. However, identified cases of Thr164Ile were few, and additional studies of rare ADRB2 genotypes are required.

PMID: 28506092 [PubMed - as supplied by publisher]

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Determinants of bone specific metastasis in prostate cancer.

Crit Rev Oncol Hematol. 2017 Apr;112:59-66

Authors: Manca P, Pantano F, Iuliani M, Ribelli G, De Lisi D, Danesi R, Del Re M, Vincenzi B, Tonini G, Santini D

Abstract
Prostate cancer is one of the most common type of cancer in Western countries. Although the majority of patients with PCa have a minimally aggressive disease, some of them will experience relapse and formation of metastasis. Bone metastasis are a major cause of quality of life impairment and death among patients with metastatic prostate cancer. Different "bone targeted therapies" and several follow-up strategies were developed in order to optimize bone metastasis prevention and treatment. Nevertheless there is still a great clinical need of identifying patients more likely to benefit from those interventions as not all patients will develop metastatic disease and not all patients with metastatic disease will develop bone metastasis. Here we review markers predictive of bone metastasis occurrence that have been tested in clinical settings, particularly focusing on the ability of such markers to predict bone metastasis over visceral metastasis occurrence.

PMID: 28325265 [PubMed - indexed for MEDLINE]

Alteration of protein function by a silent polymorphism linked to tRNA abundance.

PLoS Biol. 2017 May;15(5):e2000779

Authors: Kirchner S, Cai Z, Rauscher R, Kastelic N, Anding M, Czech A, Kleizen B, Ostedgaard LS, Braakman I, Sheppard DN, Ignatova Z

Abstract
Synonymous single nucleotide polymorphisms (sSNPs) are considered neutral for protein function, as by definition they exchange only codons, not amino acids. We identified an sSNP that modifies the local translation speed of the cystic fibrosis transmembrane conductance regulator (CFTR), leading to detrimental changes to protein stability and function. This sSNP introduces a codon pairing to a low-abundance tRNA that is particularly rare in human bronchial epithelia, but not in other human tissues, suggesting tissue-specific effects of this sSNP. Up-regulation of the tRNA cognate to the mutated codon counteracts the effects of the sSNP and rescues protein conformation and function. Our results highlight the wide-ranging impact of sSNPs, which invert the programmed local speed of mRNA translation and provide direct evidence for the central role of cellular tRNA levels in mediating the actions of sSNPs in a tissue-specific manner.

PMID: 28510592 [PubMed - in process]

Inhaled Antibiotic Therapy in Chronic Respiratory Diseases.

Int J Mol Sci. 2017 May 16;18(5):

Authors: Maselli DJ, Keyt H, Restrepo MI

Abstract
The management of patients with chronic respiratory diseases affected by difficult to treat infections has become a challenge in clinical practice. Conditions such as cystic fibrosis (CF) and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus, Burkholderia species and non-tuberculous Mycobacteria (NTM). These challenges prompted scientists to deliver antimicrobial agents through the pulmonary system by using inhaled, aerosolized or nebulized antibiotics. Subsequent research advances focused on the development of antibiotic agents able to achieve high tissue concentrations capable of reducing the bacterial load of difficult-to-treat organisms in hosts with chronic respiratory conditions. In this review, we focus on the evidence regarding the use of antibiotic therapies administered through the respiratory system via inhalation, nebulization or aerosolization, specifically in patients with chronic respiratory diseases that include CF, non-CF bronchiectasis and NTM. However, further research is required to address the potential benefits, mechanisms of action and applications of inhaled antibiotics for the management of difficult-to-treat infections in patients with chronic respiratory diseases.

PMID: 28509852 [PubMed - in process]

Palivizumab prophylaxis in infants with cystic fibrosis does not delay first isolation of Pseudomonas aeruginosa or Staphylococcus aureus.

Eur J Pediatr. 2017 May 16;:

Authors: Buchs C, Dalphin ML, Sanchez S, Perceval M, Coutier L, Mainguy C, Kassaï-Koupaï B, Reix P

Abstract
Respiratory syncytial virus (RSV) infections may worsen cystic fibrosis (CF) lung disease and favor Pseudomonas aeruginosa (Pa) or Staphylococcus aureus (Sa) acquisition, which is of particular importance in the youngest patients. We aimed to determine the effectiveness of PVZ on microbiological outcomes in young children with CF. We conducted a retrospective case-control study to compare these outcomes in children who systematically received PVZ (PVZ+; n = 40) or not (PVZ-; n = 140). One case was matched with at least three same-gender controls born the same year and month. Median (range) age at first Pa isolation was not statistically different between PVZ- (12.3 [3.8-32.6] months) and PVZ+ (10.4 [1.2-33.0] months; p = 0.953) patients. A similar trend was found for Sa (PVZ+: 6.4 [2.0-59.0] months; PVZ-: 3.8 [0.1-74.1] months; p = 0.191). The proportion of Pa isolations by 3 years of age did not differ between groups (PVZ+ 40% vs. PVZ- 41.4%), but this proportion was higher for Sa in the PVZ+ group (97%) than in the PVZ- group (85%; p = 0.001). Healthcare consumption and growth outcomes did not significantly differ between groups.
CONCLUSION: Systematic PVZ use did not delay key pathogen acquisition in young children with CF. What is known: • Palivizumab is the only available monoclonal antibody against respiratory syncytial virus infection. • Whether or not it is useful in infants with cystic fibrosis remains controversial. What is new: • Palivizumab does not delay key pathogens (Pseudomonas aeruginosa, Staphylococcus aureus) first isolation in young children with cystic fibrosis. • Palivizumab does not reduce healthcare consumption or improve growth during the first 3 years of life of young children with cystic fibrosis.

PMID: 28508992 [PubMed - as supplied by publisher]

Related Articles

The Vitamin D for Enhancing the Immune System in Cystic Fibrosis (DISC) trial: Rationale and design of a multi-center, double-blind, placebo-controlled trial of high dose bolus administration of vitamin D3 during acute pulmonary exacerbation of cystic fibrosis.

Contemp Clin Trials Commun. 2017 Jun;6:39-45

Authors: Tangpricha V, Smith EM, Binongo J, Judd SE, Ziegler TR, Walker S, Tirouvanziam R, Zughaier SM, Lee MJ, Chesdachai S, Hermes WA, Chmiel JF, Gaggar A, Grossmann RE, Joseph PM, Alvarez JA

Abstract
Vitamin D deficiency is highly prevalent in children and adults with cystic fibrosis (CF). Recent studies have found an association between vitamin D status and risk of pulmonary exacerbations in children and adults with CF. The ongoing Vitamin D for enhancing the Immune System in Cystic fibrosis (DISC) study is a multi-center, double-blind, randomized, placebo-controlled trial that will test the hypothesis of whether high dose vitamin D given as a single oral bolus of 250,000 IU to adults with CF during a pulmonary exacerbation followed by a maintenance dose of vitamin D will improve time to next pulmonary exacerbation and re-hospitalization, improve survival and lung function compared to placebo and reduce the rates of pulmonary exacerbation,. Subjects will be randomized 1:1 at each clinical site to vitamin D or placebo within 72 hours of hospital admission for pulmonary exacerbation. Clinical follow-up visits will occur at 1, 2, 3, and 7 days, and 1, 3, 6 and 12 months after randomization. Blood and sputum will be collected and determination of clinical outcomes will be assessed at each visit. The primary endpoint will be the time to next pulmonary exacerbation requiring antibiotics, re-hospitalization or death. The secondary endpoints will include lung function assessed by forced expiratory volume in 1 second (FEV1), blood markers of inflammatory cytokines, anti-microbial peptide expression by peripheral blood mononuclear cells and circulating concentrations in blood. Other exploratory endpoints will examine the phenotype of neutrophils and monocyte/macrophages in sputum. Nutritional status will be assessed by 3 day food records and food frequency questionnaire.

PMID: 28508087 [PubMed - in process]

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Investigating the feasibility of text message reminders to improve adherence to nebulized medication in children and adolescents with cystic fibrosis.

Patient Prefer Adherence. 2017;11:861-869

Authors: Morton RW, Elphick HE, Edwards E, Daw WJ, West NS

Abstract
BACKGROUND: Children with cystic fibrosis (CF) often have suboptimal adherence rates to nebulized medication. Adherence barriers cited include forgetting to take the nebulizers, due to busy home and social lives. Text message reminders have been shown to be effective at improving adherence rates in other chronic diseases such as asthma and diabetes.
OBJECTIVE: The objective of this study was to assess the feasibility and efficacy of sending text reminders for a prolonged period of time to children with CF.
MATERIALS AND METHODS: Children with CF aged 5-16 years taking at least one medication via a nebulizer with an electronic adherence monitor were consented for the study. Text message reminders were sent to participants and/or parents via the hospital's automated text service, up to twice a day, for 6 months. The adherence rates for the 6-month text period were compared to the previous 6 months before the study. Rates were calculated for weekdays, weekends, and school holidays.
RESULTS: Seventeen participants were recruited to the study, with a mean age of 12 years and a mean forced expiratory volume in 1 second (FEV1) of 81% predicted. Fifteen children completed the 6-month text period, and I-neb data were accurately analyzed for 13 participants. The mean adherence rate in the 6 months receiving texts was 80%, compared to 81% in the prior 6 months. Overall adherence rates on weekdays, weekends, and school holidays were equivalent during the 2 time periods. A subgroup of patients with moderate baseline adherence showed increased adherence during the text period, particularly at weekends.
CONCLUSION: It is feasible to send text message reminders to children with CF, and they are amenable to this approach. Although text reminders do not increase rates in patients with existing optimal adherence, they may be of value in patients with more moderate baseline rates.

PMID: 28507430 [PubMed - in process]