Prospective evaluation of nontuberculous mycobacteria disease in cystic fibrosis: The design of the PREDICT study.

BACKGROUND: Nontuberculous mycobacteria (NTM) are an important cause of airway infections in people with cystic fibrosis (pwCF). Isolation of NTM from respiratory specimens of pwCF do not mandate treatment in the absence of clinical and radiologic features of NTM pulmonary disease (NTM-PD), as some pwCF clear the infection without treatment and others do not appear to progress to NTM-PD despite persistent infection. An evidence-based protocol to standardize diagnosis of NTM-PD is needed to systematically identify pwCF who may benefit from treatment. METHODS: In this multicenter observational study, eligible pwCF who are 6 years of age and older and who have had a recent positive NTM culture are systematically evaluated for NTM-PD. Participants are identified based on positive NTM culture results obtained during routine clinical care and following enrollment are evaluated for NTM-PD and CF-related comorbidities. Participants are followed in PREDICT until they meet NTM-PD diagnostic criteria and are ready to initiate NTM treatment, or until study termination. Active participants who have not met these criteria are re-consented every 5 years to enable long-term participation. RESULTS: The primary endpoint will summarize the proportion of participants who meet the NTM-PD diagnosis definition. The time from enrollment to NTM-PD diagnosis will be derived from Kaplan-Meier estimates. CONCLUSION: A prospective protocol to identify NTM-PD in pwCF will test if this standardized approach defines a cohort with signs and symptoms associated with NTM-PD, to assist with clinical decision making and to build a framework for future therapeutic trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02073409.

Implementation and challenges of portable blood gas measurements in air medical transport.

OBJECTIVES: Ventilator management in prehospital settings using end-tidal CO2 can lead to inappropriate ventilation in the absence of point of care blood gas (POCBG) measurements. Implementation of POCBG testing in helicopter Emergency Medical Services (HEMS) is limited in part because of concern for preanalytical and analytical errors due to altitude, vibration, and other associated environmental factors and due to insufficient documentation of implementation challenges. METHODS: We performed accuracy and precision verification studies using standard materials tested pre-, in-, and post-flight (n=10) in a large HEMS agency. Quality assurance error log data were extracted and summarized for common POCBG errors during the first 31 months of use and air medical transport personnel were surveyed regarding POCBG use (n=63). RESULTS: No clinically significant differences were found between pre-, in-, and post-flight blood gas measurements. Error log data demonstrated a reduction in device errors over time. Survey participants found troubleshooting device errors and learning new clinical processes to be the largest barriers to implementation. Continued challenges for participants coincided with error log data including temperature and sampling difficulties. Survey participants indicated that POCBG testing improved patient management. CONCLUSIONS: POCBG testing does not appear to be compromised by the HEMS environment. Temperature excursions can be reduced by use of insulated transport bags with heating and cooling packs. Availability of POCBG results in air medical transport appeared to improve ventilator management, increase recognition of ventilation-perfusion mismatch, and improve patient tolerance of ventilation.

Interprofessional practice: the path toward openness.

This article seeks to shed light on the meanings healthcare practitioners attach to practicing interprofessionally and how interprofessional relationships play out in "everyday" practice. It draws on findings from a hermeneutic phenomenological study of health professionals' lived experience of practice, interpreted in relation to Martin Heidegger's concept of a path through the dense forest which leads to an open space where there is no predefined path to follow. Analysis of data from in-depth, semi-structured interviews with 12 health professionals from medicine, midwifery, nursing, occupational therapy, physiotherapy, speech and language therapy, and social work suggests that health practitioners come upon the clearing having walked their own track toward practicing interprofessionally. Our argument is that when: getting to know others; genuine dialogue; trust; and respect are in play, a spirit of interprofessional practice flourishes. The ontological view presented, sheds light on the nature of the relationships and the personal qualities that foster a spirit of interprofessional practice in these human-to-human interactions. It highlights how health practitioners need to be free to enact their humanity; to move beyond the "professional" pathway, which encourages them to leave "who they are" at home.

13†NHSBT Tissue and eye services: the role of the hospital development nurse practitioner.

NHS Blood and Transplant (NHSBT) Tissue and Eye Services (TES) save and improve the lives of thousands of patients every year.The roles and responsibilities of the nurses working in TES are diverse. Across the TES supply chain nursing roles are pivotal.They range from raising awareness of tissue donation and creating robust referral systems through to skilled communication with recently bereaved families over the telephone, as well as advanced nursing practice in clinical decision-making regarding suitability for transplantation and research.In the UK, around 25 million people have registered to donate organs and tissues. However, there is poor understanding around the tissue-donation process.Hospital development nurse practitioners (HDNPs) provide a professional link between service Providers/users and TES so that effective working partnerships can be developed. HDNPs ensure that there is a professional link from TES to support, educate and advise a wide range of health professionals about tissue donation. They are a visible and respected presence in the areas within which they work and continuously build on these successful working partnerships and contractual agreements to increase donor referrals.Consistent findings from a global body of research for organs and tissues over the past 15 years shows that there are key factors that influence family decision making (Sque et al, 2008; Siminoff et al, 2010; Long-Sutehall et al, 2012; Sque et al, 2018).Evidence suggests that key factors include:• Failure by health professionals to recognise potential donors• Reluctance of health professionals to talk about tissue donation• Family/next of kin not agreeing to donation due to concerns about the donation process (for example, the post donation appearance of the donor) or personally held views.The role of the HDNP aims to overcome some of these barriers and work towards increasing the number of referrals of potential tissue donors. This includes creating robust referral systems, raising awareness, educating, and sharing information about tissue donation so that patients and their families can make an informed choice about donating tissue for transplant and/or research. HDNPs work closely with selected NHS trusts at strategic levels to implement referral systems. This includes working alongside senior colleagues such as chief executives, directors of nursing, end-of-life-care specialists and coroners.HDNPs work closely with selected trusts in developing automatic referral systems whereby 100% of adult deaths are referred so nurses are able to reach many more families to discuss the option of donating tissue.

Urine lipoarabinomannan as a marker for low-risk of NTM infection in the CF airway.

BACKGROUND: Individuals with Cystic fibrosis (CF) are the most vulnerable population for pulmonary infection with nontuberculous mycobacteria (NTM). Screening, diagnosis, and assessment of treatment response currently depend on traditional culture techniques, but sputum analysis for NTM in CF is challenging, and associated with a low sensitivity. The cell wall lipoarabinomannan (LAM), a lipoglycan found in all mycobacterial species, and has been validated as a biomarker in urine for active Mycobacterium tuberculosis infection. METHODS: Urine from a CF cohort (n = 44) well-characterized for NTM infection status by airway cultures was analyzed for LAM by gas chromatography/mass spectrometry. All subjects with positive sputum cultures for NTM had varying amounts of LAM in their urine. No LAM was detected in subjects who never had a positive culture (14/45). One individual initially classified as NTM sputum negative subsequently developed NTM disease 657 days after the initial urine LAM testing. Repeat urine LAM testing turned positive, correlating to her positive NTM status. Subjects infected with subspecies of M. abscessus had greater LAM quantities than those infected with M. avium complex (MAC). There was no correlation with disease activity or treatment status and LAM quantity. A TB Capture ELISA using anti-LAM antibodies demonstrated very poor sensitivity in identifying individuals with positive NTM sputum cultures. CONCLUSION: These findings support the conclusion that urine LAM related to NTM infection may be a useful screening test to determine patients at low risk for having a positive NTM sputum culture, as part of a lifetime screening strategy in the CF population.

Ivacaftor in cystic fibrosis with residual function: Lung function results from an N-of-1 study.

BACKGROUND: Ivacaftor shows benefit in patients with cystic fibrosis (CF) and CFTR mutations associated with residual CF transmembrane conductance regulator (CFTR) function. Here we further assess the effect of ivacaftor in such patients using an N-of-1 study design. METHODS: Patients aged ≥12 years with CF with clinical or molecular evidence of residual CFTR function were randomized to 1 of 4 treatment sequences for two 4-week, double-blind crossover cycles (each divided into 2 weeks of ivacaftor treatment and placebo) followed by 8 weeks of open-label ivacaftor treatment. The primary endpoint was absolute change from cycle baseline of percent predicted forced expiratory volume in 1 s (ppFEV1) after 2 weeks of treatment with ivacaftor relative to placebo. RESULTS: Absolute change (SD) from study baseline in ppFEV1 favored ivacaftor by 2.3 (1.0) percentage points (95% credible interval, 0.4-4.1) after 2 weeks of treatment. Absolute mean change (SD) from open-label baseline (defined as day 1 of the open-label ivacaftor treatment period) in ppFEV1 after 8 weeks of treatment was 4.7 (4.2) percentage points (P<.0001). Safety of ivacaftor was consistent with that observed in prior studies. CONCLUSIONS: Ivacaftor improved lung function during the double-blind and open-label treatment periods in patients with CF and CFTR mutations associated with residual CFTR function (ClinicalTrials.gov, NCT01685801).

Interprofessional practice: beyond competence.

Interprofessional practice is commonly discussed in the literature in terms of competencies. In this study we move away from the theoretical notions of criteria, concepts and guidelines to adopt an ontological approach which seeks to stay as close to the lived experience as possible. Our research asked 12 participants from a variety of health disciplines to tell their stories of working interprofessionally. We sought to glean meaning from the lived experience. Our phenomenological hermeneutic approach and interpretation were informed by Heidegger and Gadamer. Rather than offering a thematic overview, in this article we share three stories from the research that were congruent with other stories. The first, told by a doctor, is of a resuscitation in an emergency department. It shows how the effective working together of the interprofessional team was more than each member following a resuscitation protocol. There was 'something' about how they worked together that made this story stand out, even though the patient died. The second story showcases how 'who' the person is makes a difference. This nurse makes an effort to get to know other staff as people, to find common interests. In such a way interprofessional practice comes to flourish. The third story shows how a physiotherapist and a psychologist joined in conversation to seek innovative possibilities for a challenging situation. In such a way each built on the others expertise and were excited at the success they achieved for the patient. From these ontological accounts we have come to see that interprofessional practice flourishes when practitioners are their authentic, caring selves. Who the person is matters.

Working in a spirit of interprofessional practice: a hermeneutic phenomenological study.

Interprofessional practice is recognized as essential to providing patient-centered, collaborative and high quality care, contributing to optimal health outcomes. Understandings of how best to cultivate practitioners able to 'be' and 'become' interprofessional remain problematic. To advance that understanding, this hermeneutic phenomenological study addressed the question: 'What are health professionals' experiences of working with people from other disciplines?' In-depth, semi structured interviews with 12 health professionals from nursing, occupational therapy, physiotherapy, speech and language therapy, medicine, social work, and midwifery were undertaken using a conversation style. Three unifying themes revealed things which appear to be at the 'heart' of interprofessional practice; the call to interprofessional practice, working in a spirit of interprofessional practice and safeguarding and preserving interprofessional practice. This paper focuses on the first two themes. The findings contribute to a deeper understanding of interprofessional practice as a way of being that extends beyond known and measureable skills and knowledge, to dispositions and qualities. Dispositional qualities come from within a person and what they care about, and from experiences that shape their understandings. This study points toward interprofessional practice as being about a spirit. Who people are, what they bring and how they act is what matters.

Restoring: How older adults manage their recovery from hip fracture.

AIMS AND OBJECTIVES: To generate a substantive theory that explained recovery from hip fracture from the perspective of older adults and find out how they managed it. BACKGROUND: Hip fracture is a well-researched phenomenon. The perspective of how older adults recover from hip fracture has been examined least of all. Patients spend less time in hospital following injury and generally recover in their home setting. DESIGN: A Glaserian grounded theory approach was used for this study. METHODS: Semi-structured interviews (n-21) were conducted with older adult's post discharge following hip fracture. Data were collected, analysed and theorised using the grounded theory methodology. RESULTS: Older adults recovering from hip fracture were restored back to normal through a process in which they continuously balanced regaining of physical and social functioning against reasserting usual psycho-social behaviours within different contexts. Importantly, the older adult's personal recovery process starts within the acute setting once the person regains physical functioning, especially regaining mobility. From this point onwards, older adults will respond to health professionals, instructions and interventions in many ways. The responses will be based on their developmental life stage to enable them to counter the diverse expectations placed on them by health professionals, social networks and their self-beliefs. CONCLUSION: Nurses need to understand that older adults will recover in their own way following discharge, often re-interpreting health information to fit their own situations.

Effects of gender and age at diagnosis on disease progression in long-term survivors of cystic fibrosis.

RATIONALE: Long-term survivors of cystic fibrosis (CF) (age > 40 yr) are a growing population comprising both patients diagnosed with classic manifestations in childhood, and nonclassic phenotypes typically diagnosed as adults. Little is known concerning disease progression and outcomes in these cohorts. OBJECTIVES: Examine effects of age at diagnosis and gender on disease progression, setting of care, response to treatment, and mortality in long-term survivors of CF. METHODS: Retrospective analysis of the Colorado CF Database (1992-2008), CF Foundation Registry (1992-2007), and Multiple Cause of Death Index (1992-2005). MEASUREMENTS AND MAIN RESULTS: Patients with CF diagnosed in childhood and who survive to age 40 years have more severe CFTR genotypes and phenotypes compared with adult-diagnosed patients. However, past the age of 40 years the rate of FEV(1) decline and death from respiratory complications were not different between these cohorts. Compared with males, childhood-diagnosed females were less likely to reach age 40 years, experienced faster FEV(1) declines, and no survival advantage. Females comprised the majority of adult-diagnosed patients, and demonstrated equal FEV(1) decline and longer survival than males, despite a later age at diagnosis. Most adult-diagnosed patients were not followed at CF centers, and with increasing age a smaller percentage of CF deaths appeared in the Cystic Fibrosis Foundation Registry. However, newly diagnosed adults demonstrated sustained FEV(1) improvement in response to CF center care. CONCLUSIONS: For patients with CF older than 40 years, the adult diagnosis correlates with delayed but equally severe pulmonary disease. A gender-associated disadvantage remains for females diagnosed in childhood, but is not present for adult-diagnosed females.

Physiotherapists' participation in peer review in New Zealand: implications for the profession.

BACKGROUND AND PURPOSE: Peer review is increasingly used for professional development and to monitor physiotherapists' competence to practice. This study set out to describe the experience of participating in peer review. METHOD: Qualitative descriptive methods were employed to elicit and analyze interview data from physiotherapists with experience as reviewers and having their practice reviewed. RESULTS: Reviewers managed the process to provide an appropriate level of challenge to junior and senior therapists, and to avoid disrupting professional relationships. Those being reviewed reduced anxiety about the process and risk of negative feedback by putting their best practice on show, and where they could, by carefully choosing the reviewer and patient interaction to be reviewed. CONCLUSION: When peer review has competing purposes it is neither an effective professional development tool nor an accurate measure of competence. Power and interpersonal relationships need to be acknowledged if peer review is used to assess practitioner competence.

Mutagenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the mammary gland of Big Blue rats on high-and low-fat diets.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a food-borne mutagen and mammary gland carcinogen in female rats. A high-fat diet has been shown to increase the incidence of PhIP-induced mammary gland tumors. The current study used Big Blue rats harboring the lambda lacI mutational reporter transgene, to address whether the promotional effect of a high-fat diet is mediated via modulation in mammary gland mutagenesis. Big Blue rats were given 10 doses of PhIP (75 mg/kg, p.o.) and placed on defined low-fat (5% corn oil) or high-fat (23.5% corn oil) diet for 6 weeks prior to collecting mammary glands. The lacI mutant frequency (mean +/- standard error, n = 3 rats) was 231 +/- 15 (x10(-6)) and 193 +/- 12 (x10(-6)) in the low-and high-fat group, respectively. Values were increased 12-fold over control but were not significantly different between the two diets. In a parallel study, diet did not alter the mutant frequency induced by 7,12-dimethylbenz[a]anthracene (DMBA) (125 mg/kg, p.o.) in the mammary gland. The findings suggest that the promotion by the high-fat diet is not mediated via an increase in mutations. Consistent with the high potency of DMBA as a mammary carcinogen, the mutant frequency was 20-30% higher with DMBA than with PhIP. Sixty-nine and 56 PhIP-induced lacI mutants were sequenced from the low-and high-fat diet groups, respectively. While the percentage of various types of mutations was identical between the diet groups, some difference in the distribution of mutations along the lacI gene was observed. The mutation spectrum in the mammary gland from rats on both diets was consistent with the formation of PhIP-guanine adducts which were detected by a (32)P-post-labeling assay. Guanine base substitutions accounted for approximately 85% of all mutations irrespective of diet. Single base pair deletions at guanine occurred in 11-17% of mutants. G:C to T:A transversions were the predominant base substitution mutation accounting for 35-43% of all mutations. The majority of all guanine mutations (74%) occurred at guanine bases adjacent to another G:C pair. Five out of 125 (4%) mutations involved a guanine deletion in the 5'-GGGA-3' sequence, a PhIP signature mutation reported previously. Twelve out of 125 (10%) mutations involved the guanine base in the sequence 5'-CAG(Purine)-3' (Pu). The findings from these studies suggest that 5'-CAG(Pu)-3' is an additional characteristic target site for PhIP-guanine adduct-induced mutations in vivo in the mammary gland.