Funding Opportunity PAR-18-707 from the NIH Guide for Grants and Contracts. The purpose of this FOA is the rapid and efficient translation of innovative laboratory research findings into therapies, devices or other resources for use by clinicians to treat visual system diseases or disorders. Multidisciplinary teams of scientists and clinicians will focus on generating preclinical data that will lead to the development of biological interventions, such as gene therapy, cell-based therapy, pharmacological approaches, and/or medical devices. The ultimate goal of this program is to make technological, biological and pharmacological resources available to clinicians and their patients.

Funding Opportunity PAR-18-706 from the NIH Guide for Grants and Contracts. The goal of this FOA is to define and characterize neural cell populations, neural circuits, and brain networks and regions that are vulnerable to brain aging and Alzheimers disease (AD). Understanding mechanisms underlying selective vulnerability from cells to networks in AD is critical to fully define the disease process and to develop effective therapies.

Funding Opportunity RFA-DA-19-005 from the NIH Guide for Grants and Contracts. This FOA solicits applications proposing phased research projects, with transition milestones, to develop and rigorously test the effects of strategies to improve opioid treatment quality measures, both on changes in the measures themselves and on patient outcomes. The overall goal is to advance the field of clinical quality measurement and management in opioid use disorder treatment by generating research better aligning quality measurement with quality improvement.

Notice NOT-MH-18-027 from the NIH Guide for Grants and Contracts

Funding Opportunity PAS-18-698 from the NIH Guide for Grants and Contracts. This Funding Opportunity Announcement (FOA) seeks to stimulate HIV/AIDS research within the mission of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) that addresses high priority HIV/AIDS research priorities outlined by the NIH Office of AIDS Research (OAR). These priorities are described in NOT-OD-15-137: NIH HIV/AIDS Research Priorities and Guidelines for Determining AIDS Funding.

Notice NOT-MH-18-026 from the NIH Guide for Grants and Contracts

Funding Opportunity RFA-HD-19-001 from the NIH Guide for Grants and Contracts. A major objective of this funding opportunity announcement (FOA) is to invite SBIR applications to foster collaboration between clinical and bioengineering research communities to develop and test safe, accurate, and effective devices for use in neonatal, perinatal, and pediatric care settings. These can be new devices or improvements on existing devices. The studies may range from concept to developmental phases, with a clear commercialization plan to enable healthcare providers to use them in regular clinical care settings in the population, which is the focus of this FOA.

Notice NOT-NS-18-048 from the NIH Guide for Grants and Contracts

Funding Opportunity PA-18-695 from the NIH Guide for Grants and Contracts. This funding opportunity announcement (FOA) encourages innovative basic and translational exploratory research into mechanisms of HIV transmission, persistence, pathogenesis and co-morbidities in the oral cavity.

Funding Opportunity PA-18-699 from the NIH Guide for Grants and Contracts. This funding opportunity announcement (FOA) encourages innovative basic and translational research into mechanisms of HIV transmission, persistence, pathogenesis and co-morbidities in the oral cavity.

Notice NOT-EY-18-006 from the NIH Guide for Grants and Contracts

Funding Opportunity RFA-HL-19-014 from the NIH Guide for Grants and Contracts. This Funding Opportunity Announcement (FOA) seeks late-stage T4 Translation research (T4TR) and implementation studies that will lead to generalizable new knowledge to accelerate the adoption/adaptation, and sustained, high-fidelity use of proven-effective interventions for the prevention, treatment, and control of heart, lung, blood, and sleep disorders or diseases (HLBS conditions). It calls for multi-level strategies for delivery of proven-effective interventions to promote the prevention and management of HLBS conditions. The system-level change(s) being evaluated are to be designed, and findings reported so that others would have a contextually-informed understanding of workflow, workforce, and trade-off considerations. These considerations should reflect cultural and organizational contextual factors and values as they inform feasibility and flexibility of adopting, adaptable and sustainable, proven-effective interventions to address HLBS conditions.

Funding Opportunity PAR-18-697 from the NIH Guide for Grants and Contracts. This Funding Opportunity Announcement (FOA) , utilizing the U24 grant funding mechanism, encourages applications for a collaborating Data Coordinating Center (DCC) application that accompanies investigator-initiated, multi-site clinical trials (Phase III and beyond) applications submitted under PAR-18-124 (https://grants.nih.gov/grants/guide/pa-files/PAR-18-124.html). The DCC application must be specific to the collaborating Clinical Coordinating Center (CCC) application. The objective of the DCC application Is lo propose a, comprehensive plan that provides overall project coordination. and administrative, data management and biostatistical support for the proposed clinical trial. Both a DCC application and a corresponding CCC application need to be submitted simultaneously for consideration by NCCIH. Trials for which this FOA applies must be relevant to the research mission of the NCCIH and considered a high priority by the Center. For additional information about the mission, strategic vision, and research priorities of the NCCIH, applicants are encouraged to consult the NCCIH website: (https://www,nocih.nih.gov) . Applicants are encouraged to contact the appropriate Scientific/Research contact for the area of science for which they are planning to develop an application prior lo submitting to this FOA.

Funding Opportunity PAR-18-696 from the NIH Guide for Grants and Contracts. This Funding Opportunity Announcement (FOA) encourages cooperative agreement applications for investigator-initiated multi-site clinical trials (Phase III and beyond) to study the effects of natural products in NCCIH designated areas of high research priority. Applicants should describe plans for a Clinical Coordinating Center to develop and implement the proposed multi-site clinical trial. The objective of the Clinical Coordinating Center is to provide the design scientific rationale and a comprehensive scientific and operational plan for the clinical trial. The Clinical Coordinating Center is expected to be responsible for project management, participant recruitment and retention strategies, performance milestones, scientific conduct, and dissemination of results. Clinical Coordinating Center applications submitted under this FOA will utilize a two-phase, milestone-driven cooperative agreement (UG3/UH3) funding mechanism. In addition, an accompanying Data Coordinating Center application, submitted under PAR-18-123 (https://grants.nih.gov/grants/guide/pa-files/PAR-18-123.html), proposing a data analysis and data management plan for the clinical project is required. Both a Clinical Coordinating Center application and a corresponding Data Coordinating Center (DCC) application need to be submitted simultaneously for consideration by NCCIH.

Notice NOT-OD-18-134 from the NIH Guide for Grants and Contracts

Bronchiectasis in indigenous and non-indigenous residents of Australia and New Zealand.

Respirology. 2018 Mar 04;:

Authors: Blackall SR, Hong JB, King P, Wong C, Einsiedel L, Rémond MGW, Woods C, Maguire GP

Abstract
BACKGROUND AND OBJECTIVE: Bronchiectasis not associated with cystic fibrosis is an increasingly recognized chronic lung disease. In Oceania, indigenous populations experience a disproportionately high burden of disease. We aimed to describe the natural history of bronchiectasis and identify risk factors associated with premature mortality within a cohort of Aboriginal Australians, New Zealand Māori and Pacific Islanders, and non-indigenous Australians and New Zealanders.
METHODS: This was a retrospective cohort study of bronchiectasis patients aged >15 years at three hospitals: Alice Springs Hospital and Monash Medical Centre in Australia, and Middlemore Hospital in New Zealand. Data included demographics, ethnicity, sputum microbiology, radiology, spirometry, hospitalization and survival over 5 years of follow-up.
RESULTS: Aboriginal Australians were significantly younger and died at a significantly younger age than other groups. Age- and sex-adjusted all-cause mortality was higher for Aboriginal Australians (hazard ratio (HR): 3.9), and respiratory-related mortality was higher for both Aboriginal Australians (HR: 4.3) and Māori and Pacific Islander people (HR: 1.7). Hospitalization was common: Aboriginal Australians had 2.9 admissions/person-year and 16.9 days in hospital/person-year. Despite Aboriginal Australians having poorer prognosis, calculation of the FACED score suggested milder disease in this group. Sputum microbiology varied with Aspergillus fumigatus more often isolated from non-indigenous patients. Airflow obstruction was common (66.9%) but not invariable.
CONCLUSIONS: Bronchiectasis is not one disease. It has a significant impact on healthcare utilization and survival. Differences between populations are likely to relate to differing aetiologies and understanding the drivers of bronchiectasis in disadvantaged populations will be key.

PMID: 29502335 [PubMed - as supplied by publisher]

Staphylococcus aureus in the airways of cystic fibrosis patients - A retrospective long-term study.

Int J Med Microbiol. 2018 Feb 24;:

Authors: Schwerdt M, Neumann C, Schwartbeck B, Kampmeier S, Herzog S, Görlich D, Dübbers A, Große-Onnebrink J, Kessler C, Küster P, Schültingkemper H, Treffon J, Peters G, Kahl BC

Abstract
BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disease associated with chronic airway infections by Staphylococcus aureus as one of the earliest and most prevalent pathogens. We conducted a retrospective study to determine the S. aureus infection status of CF patients treated since 1994 at two certified CF-centres in Münster, Germany, to get insights into the dynamics of S. aureus airway infection and the clinical impact on lung function on a long-term perspective.
MATERIALS AND METHODS: We used data from our microbiological database collected between 1994 and 2016 for patients treated at two centres in Münster, Germany, respectively, to determine the infection status for S. aureus. Furthermore, the resistance to selected antibiotics was determined for all patients' isolates and for 15 patients on a longitudinal basis. In addition, the prevalence of adaptive phenotypes such as small colony variants (SCVs) and mucoid S. aureus was assessed.
RESULTS: For this study, 2867 patient years with respiratory specimens (mean of 9.3 years for every patient, range 1-22 years) were evaluated for 283 CF patients (median age of 7 years at the beginning of the observation period, range 0-57 years, 51% male). 18% of patients were rarely infected by S. aureus (≤24% of observation years), 20% of patients intermittently (25-49%) and 61% persistently (≥50% of observation period). Susceptibility testing for 12969 S. aureus isolates resulted in resistance to methicillin in 9%, trimethoprim/sulfamethoxazole in 10%, levofloxacin in 14%, gentamicin in 20%, erythromycin and/or clindamycin in 30% and penicillin in 80% of all isolates. S. aureus isolates of 15 patients revealed dynamics of resistance with increase, decrease and loss of resistant isolates to the analysed antibiotics during the study period. SCVs were isolated at least once from 42% (n = 118) of patients and mucoid isolates from 2% (n = 7) of patients. In the last study year, 89 patients were infected by S. aureus only, 44 patients by S. aureus and Pseudomonas aeruginosa and 18 by P. aeruginosa only. Patients infected by S. aureus only were younger and had better lung function compared to the other two groups.
CONCLUSIONS: We determined a high percentage of patients with persistent S. aureus infection. During persistence, mostly fluctuation of resistance against various antibiotics was observed in the isolates indicating acquisition and loss of resistance genes by S. aureus. The prevalence of adaptive phenotypes during long-term persistence was high for SCVs (42% of patients), but low for mucoid isolates (2% of patients), which might be underestimated for mucoid phenotypes due to the retrospective study design and the difficulty to detect mucoid isolates in primary cultures. While patients with S. aureus only had better lung function and were younger, no difference was found between the group of P. aeruginosa and S. aureus co-infection and P. aeruginosa only with previous S. aureus infection.

PMID: 29501453 [PubMed - as supplied by publisher]

Descriptions of the Pain Experience in Adults and Adolescents with Cystic Fibrosis.

Pain Manag Nurs. 2018 Feb 28;:

Authors: Allgood SJ, Kozachik S, Alexander KA, Thaxton A, Vera M, Lechtzin N

Abstract
People living with cystic fibrosis experience pain that is associated with decreased quality of life, poorer health outcomes, and increased mortality. Though pain is highly prevalent as a symptom, it is currently unknown how persons with CF describe their pain experiences or the ways those experiences impact their lives. To explore and describe ways adolescents and adults with CF experience pain. An exploratory descriptive design was implemented to perform interviews with 10 individuals with CF and self-reported moderate to severe pain. The interviews explored their pain experiences within five domains: Pain Characteristics, Activities, Relationships, Work/School Life, and Health Care Team. Transcribed interviews underwent a content analysis with team-based constant comparisons. Individuals with CF identify the disease as being painful; express how pain negatively affects all aspects of their lives, including loss of functionality and productivity; and are able to disclose their pain to those with whom they have relationships. Adolescents feel an emotional toll from the loss of socialization as a result of pain and feel their health care team adequately supports their pain. Adults express a unique emotional pain component to CF and feel stigmatized and unsupported by their health care team when asking for pain management solutions.There are differences in how pain is perceived by adolescents and adults with CF that have otherwise not been reported in the current literature. Further explorations of pain across the lifespan and health care provider attitudes toward pain management are needed to guide the development of effective pain management interventions for those with CF.

PMID: 29501357 [PubMed - as supplied by publisher]

Airway clearance techniques in neuromuscular disorders: A state of the art review.

Respir Med. 2018 Mar;136:98-110

Authors: Chatwin M, Toussaint M, Gonçalves MR, Sheers N, Mellies U, Gonzales-Bermejo J, Sancho J, Fauroux B, Andersen T, Hov B, Nygren-Bonnier M, Lacombe M, Pernet K, Kampelmacher M, Devaux C, Kinnett K, Sheehan D, Rao F, Villanova M, Berlowitz D, Morrow BM

Abstract
This is a unique state of the art review written by a group of 21 international recognized experts in the field that gathered during a meeting organized by the European Neuromuscular Centre (ENMC) in Naarden, March 2017. It systematically reports the entire evidence base for airway clearance techniques (ACTs) in both adults and children with neuromuscular disorders (NMD). We not only report randomised controlled trials, which in other systematic reviews conclude that there is a lack of evidence base to give an opinion, but also include case series and retrospective reviews of practice. For this review, we have classified ACTs as either proximal (cough augmentation) or peripheral (secretion mobilization). The review presents descriptions; standard definitions; the supporting evidence for and limitations of proximal and peripheral ACTs that are used in patients with NMD; as well as providing recommendations for objective measurements of efficacy, specifically for proximal ACTs. This state of the art review also highlights how ACTs may be adapted or modified for specific contexts (e.g. in people with bulbar insufficiency; children and infants) and recommends when and how each technique should be applied.

PMID: 29501255 [PubMed - in process]

Amino acid-level signal-to-noise analysis of incidentally identified variants in genes associated with long QT syndrome during pediatric whole exome sequencing reflects background genetic noise.

Heart Rhythm. 2018 Mar 01;:

Authors: Landstrom AP, Fernandez E, Rosenfeld JA, Yang Y, Dailey-Schwartz AL, Miyake CY, Allen HD, Penny DJ, Kim JJ

Abstract
BACKGROUND: Due to rapid expansion of clinical genetic testing, an increasing number of genetic variants of undetermined significance are being identified in children with unclear diagnostic value. Variants found in genes associated with heritable channelopathies, such as long QT syndrome (LQTS), are particularly difficult to interpret given the risk of sudden cardiac death associated with pathologic mutations.
OBJECTIVE: To determine whether variants in LQTS-associated genes from whole exome sequencing (WES) represent disease-associated biomarkers or background genetic "noise."
METHODS: WES variants from Baylor Genetics Laboratories were obtained for 17 LQTS-associated genes. Rare variants from healthy controls were obtained from the GnomAD database. LQTS case variants were extracted from literature. Amino acid-level mapping and signal-to-noise calculations were conducted. Clinical history and diagnostic studies were analyzed for WES subjects evaluated at our institution.
RESULTS: Variants in LQTS case-associated genes were present in 38.3% of 7,244 WES probands. There was a similar frequency of variants in the WES and healthy cohorts for LQTS1-3 (11.2 and 12.9%, respectively) and LQTS4-17 (27.1 and 38.4%, respectively). WES variants preferentially localized to amino acids altered in control individuals compared to cases. Based on amino acid-level analysis, WES-identified variants are indistinguishable from healthy background variation while LQTS1 and 2 case-identified variants localized to clear pathologic "hot spots." No individuals who underwent clinical evaluation had clinical suspicion for LQTS.
CONCLUSIONS: The prevalence of incidentally identified LQTS-associated variants is ∼38% among WES tests. These variants most likely represent benign healthy background genetic variation rather than disease associated mutations.

PMID: 29501670 [PubMed - as supplied by publisher]