Clinical Pilot of Bacterial Transcriptional Profiling as a Combined Genotypic and Phenotypic Antimicrobial Susceptibility Test.

Antimicrobial resistance is a growing health threat, but standard methods for determining antibiotic susceptibility are slow and can delay optimal treatment, which is especially consequential in severe infections such as bacteremia. Novel approaches for rapid susceptibility profiling have emerged that characterize either bacterial response to antibiotics (phenotype) or detect specific resistance genes (genotype). GoPhAST-R is a novel assay, performed directly on positive blood cultures, that integrates rapid transcriptional response profiling with detection of key resistance gene transcripts, thereby providing simultaneous data on both phenotype and genotype. Here, we performed the first clinical pilot of GoPhAST-R on 42 positive blood cultures: 26 growing Escherichia coli, 15 growing Klebsiella pneumoniae, and 1 with both. An aliquot of each positive blood culture was exposed to 9 different antibiotics, lysed, then underwent rapid transcriptional profiling on the NanoString® platform; results were analyzed using an in-house susceptibility classification algorithm. GoPhAST-R achieved 95% overall agreement with standard antimicrobial susceptibility testing methods, with the highest agreement for beta-lactams (98%) and the lowest for fluoroquinolones (88%). Epidemic resistance genes including the extended spectrum beta-lactamase bla CTX-M-15 and the carbapenemase bla KPC were also detected within the population. This study demonstrates the clinical feasibility of using transcriptional response profiling for rapid resistance determination, although further validation with larger and more diverse bacterial populations will be essential in future work. GoPhAST-R represents a promising new approach for rapid and comprehensive antibiotic susceptibility testing in clinical settings.

Antibody responses in Klebsiella pneumoniae bloodstream infection: a cohort study.

Background: Klebsiella pneumonia (Kpn) is the fourth leading cause of infection-related deaths globally, yet little is known about human antibody responses to invasive Kpn. In this study, we sought to determine whether the O-specific polysaccharide (OPS) antigen, a vaccine candidate, is immunogenic in humans with Kpn bloodstream infection (BSI). We also sought to define the cross-reactivity of human antibody responses among structurally related Kpn OPS subtypes and to assess the impact of capsule production on OPS-targeted antibody binding and function. Methods: We measured plasma antibody responses to OPS (and MrkA, a fimbrial protein) in a cohort of patients with Kpn BSI and compared these with controls, including a cohort of healthy individuals and a cohort of individuals with Enterococcus BSI. We performed flow cytometry to measure the impact of Kpn capsule production on whole cell antibody binding and complement deposition, utilizing patient isolates with variable levels of capsule production and isogenic capsule-deficient strains derived from these isolates. Findings: We enrolled 69 patients with Kpn BSI. Common OPS serotypes accounted for 57/69 (83%) of infections. OPS was highly immunogenic in patients with Kpn BSI, and peak OPS-IgG antibody responses in patients were 10 to 30-fold higher than antibody levels detected in healthy controls, depending on the serotype. There was significant cross-reactivity among structurally similar OPS subtypes, including the O1v1/O1v2, O2v1/O2v2 and O3/O3b subtypes. Physiological amounts of capsule produced by both hyperencapsulated and non-hyperencapsulated Kpn significantly inhibited OPS-targeted antibody binding and function. Interpretation: OPS was highly immunogenic in patients with Kpn BSI, supporting its potential as a candidate vaccine antigen. The strong cross-reactivity observed between similar OPS subtypes in humans with Kpn BSI suggests that it may not be necessary to include all subtypes in an OPS-based vaccine. However, these observations are tempered by the fact that capsule production, even in non-highly encapsulated strains, has the potential to interfere with OPS antibody binding. This may limit the effectiveness of vaccines that exclusively target OPS. Funding: National Institute of Allergy and Infectious Diseases at the National Institutes of Health. Research in Context: Evidence before this study: Despite the potential of O-specific polysaccharide (OPS) as a vaccine antigen against Klebsiella pneumoniae (Kpn), the immunogenicity of OPS in humans remains largely unstudied, creating a significant knowledge gap with regard to vaccine development. A search of PubMed for publications up to March 18, 2024, using the terms " Klebsiella pneumoniae " and "O-specific polysaccharide" or "O-antigen" or "lipopolysaccharide" revealed no prior studies addressing OPS antibody responses in humans with Kpn bloodstream infections (BSI). One prior study 1 evaluated antibody response to a single lipopolysaccharide (which contains one subtype of OPS) in humans with invasive Kpn infection; however, in this study OPS typing of the infecting strains and target antigen were not described. Added value of this study: Our investigation into OPS immunogenicity in a human cohort marks a significant advance. Analyzing plasma antibody responses in 69 patients with Kpn BSI, we found OPS to be broadly immunogenic across all the types and subtypes examined, and there was significant cross-reactivity among structurally related OPS antigens. We also demonstrated that Kpn capsule production inhibit OPS antibody binding and the activation of complement on the bacterial surface, even in classical Kpn strains expressing lower levels of capsule.Implications of all the available evidence: While the immunogenicity and broad cross-reactivity of OPS in humans with Kpn BSI suggests it is a promising vaccine candidate, the obstruction of OPS antibody binding and engagement by physiologic levels of Kpn capsule underscores the potential limitations of an exclusively OPS-antigen based vaccine for Kpn. Our study provides insights for the strategic development of vaccines aimed at combating Kpn infections, an important antimicrobial resistant pathogen.

Clinical and Genomic Characterization of a Cohort of Patients With Klebsiella pneumoniae Bloodstream Infection.

BACKGROUND: The clinical and microbial factors associated with Klebsiella pneumoniae bloodstream infections (BSIs) are not well characterized. Prior studies have focused on highly resistant or hypervirulent isolates, limiting our understanding of K. pneumoniae strains that commonly cause BSI. We performed a record review and whole-genome sequencing to investigate the clinical characteristics, bacterial diversity, determinants of antimicrobial resistance, and risk factors for in-hospital death in a cohort of patients with K. pneumoniae BSI. METHODS: We identified 562 patients at Massachusetts General Hospital with K. pneumoniae BSIs between 2016 and 2022. We collected data on comorbid conditions, infection source, clinical outcomes, and antibiotic resistance and performed whole-genome sequencing on 108 sequential BSI isolates from 2021 to 2022. RESULTS: Intra-abdominal infection was the most common source of infection accounting for 34% of all BSIs. A respiratory tract source accounted for 6% of BSIs but was associated with a higher in-hospital mortality rate (adjusted odds ratio, 5.4 [95% confidence interval, 2.2-12.8]; P < .001 for comparison with other sources). Resistance to the first antibiotic prescribed was also associated with a higher risk of death (adjusted odds ratio, 5.2 [95% confidence interval, 2.2-12.4]; P < .001). BSI isolates were genetically diverse, and no clusters of epidemiologically and genetically linked cases were observed. Virulence factors associated with invasiveness were observed at a low prevalence, although an unexpected association between O-antigen type and the source of infection was found. CONCLUSIONS: These observations demonstrate the versatility of K. pneumoniae as an opportunistic pathogen and highlight the need for new approaches for surveillance and the rapid identification of patients with invasive antimicrobial-resistant K. pneumoniae infection.

The effect of a night shift nap on post-night shift performance, sleepiness, mood, and first recovery sleep: A randomized crossover trial.

OBJECTIVES: This study aimed to test the effect of a 30-minute nap versus a 2-hour nap opportunity taken during a simulated night shift on performance, fatigue, sleepiness, mood, and sleep at the end of shift and during post-night shift recovery. METHODS: We conducted a randomized crossover trial of three nap conditions (30-minute, 2-hour, and no-nap) during 12-hour simulated night shifts. We tested for differences in performance, fatigue, sleepiness, mood, and sleep during in-lab and at-home recovery. Performance was measured with the Brief Psychomotor Vigilance Test (PVT-B). Subjective ratings were assessed with single-item surveys. RESULTS: Twenty-eight individuals consented to participate [mean age 24.4 (standard deviation 7.2) years; 53.6% female; 85.7% Emergency Medical Services clinicians]. PVT-B false starts at the end of the 12-hour night shift (at 07:00 hours) and at the start of in-lab recovery (08:00 hours) were lower following the 2-hour nap versus other conditions (P<0.05). PVT-B response time at +0 minutes post-recovery nap was poorer compared to pre-recovery nap for the no-nap condition (P=0.003), yet not detected for other nap conditions (P>0.05). Sleepiness, fatigue, and some mood states were lower at most hourly assessments during the in-lab recovery period following the 2-hour nap condition compared to the other conditions. Sleep during recovery did not differ by duration of night shift nap. CONCLUSIONS: A 2-hour nap opportunity versus a 30-minute or no-nap opportunity is beneficial for performance, alertness, and mood post-night shift. No differences were detected in sleep during recovery.

Improved donor lung size matching by estimation of lung volumes based on chest X-ray measurements.

RATIONALE: Organ size matching is an important determinant of successful allocation and outcomes in lung transplantation. While computed tomography (CT) is the gold standard, it is rarely used in an organ-donor context, and chest X-ray (CXR) may offer a practical and accurate solution in estimating lung volumes for donor and recipient size matching. We compared CXR lung measurements to CT-measured lung volumes and traditional estimates of lung volume in the same subjects. METHODS: Our retrospective study analyzed clinically obtained CXR and CT lung images of 250 subjects without evidence of lung disease (mean age 9.9 ± 7.8 years; 129 M/121F). From CT, each lung was semi-automatically segmented and total lung volumes were quantified. From anterior-posterior CXR view, each lung was manually segmented and areas were measured. Lung lengths from the apices to the mid-basal regions of each lung were measured from CXR. Quantified CT lung volumes were compared to the corresponding CXR lung lengths, CXR lung areas, height, weight, and predicted total lung capacity (pTLC). RESULTS: There are strong and significant correlations between CT volumes and CXR lung areas in the right lung (R2 = .89, p < .0001), left lung (R2 = .87, p < .0001), and combined lungs (R2 = .89, p < .0001). Similar correlations were seen between CT volumes and CXR measured lung lengths in the right lung (R2 = .79, p < .0001) and left lung (R2 = .81, p < .0001). This correlation between anatomical lung volume (CT) and CXR was stronger than lung-volume correlation to height (R2 = .66, p < .0001), weight (R2 = .43, p < .0001), or pTLC (R2 = .66, p < .0001). CONCLUSION: CXR measures correlate much more strongly with true lung volumes than height, weight, or pTLC. The ability to obtain efficient and more accurate lung volume via CXR has the potential to change our current listing practices of using height as a surrogate for lung size, with a case example provided.

Complete genome sequences of cluster G1 and cluster K4 Mycobacterium smegmatis phages omnicritical and Barkley26.

We present the complete genome sequence of two Actinobacteriophages, OmniCritical and Barkley26, isolated in Clark County, NV. Over two semesters, The University of Nevada, Las Vegas (UNLV) students isolated and purified phages and manually annotated the genomes. The courses follow the HHMI Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Sciences (SEA-PHAGES) curricula.

Effect of Short versus Long Duration Naps on Blood Pressure during Simulated Night Shift Work: A Randomized Crossover Trial.

OBJECTIVE: Blunting of the sleep-related dip in blood pressure (BP) has been linked to numerous cardiovascular outcomes including myocardial infarction. Blunting of BP dipping occurs during night shift work and previous research suggest that a 60-min or longer on-shift nap is needed to restore normal/healthy BP dipping. We sought to determine the effect of different durations of napping on BP during and following simulated night shifts. We hypothesized that the greatest benefit in terms of restoration of normal BP dipping during night shift work would be observed during a longer duration nap versus a shorter nap opportunity. METHODS: We used a randomized crossover laboratory-based study design. Participants consented to complete three separate 72-hr conditions that included a 12-hr simulated night shift. Nap conditions included a 30-min and 2-hr nap compared to a no-nap condition. Ambulatory BP monitoring was assessed hourly and every 10-30 mins during in-lab naps. Blunted BP dipping during in-lab naps was the primary outcome. Goal enrollment of 25 (35 with attrition) provided 80% power to detect a mean difference of 5 mmHg in BP between nap conditions. RESULTS: Of the 58 screened, 28 were consented, and 26 completed all three 72-hr conditions. More than half (53.6%) were female. Mean age was 24.4 years (SD7.2). Most (85.7%) were certified as emergency medical technicians or paramedics. The mean percentage dip in systolic BP (SBP) and diastolic BP (DBP) did not differ between the 30-min and 2-hr nap conditions (p > 0.05), yet a greater proportion of participants experienced a 10-20% dip in SBP or DBP during the 2-hr nap versus the 30-min nap (p < 0.05). For every additional minute of total sleep during the 30-min nap, the percentage of SBP dip improved by 0.60%, and the percentage of DBP dip improved by 0.68% (p < 0.05). These improvements approximate to a 6% per minute relative advancement toward normal/healthy BP dipping. CONCLUSIONS: Restoration of a normal/healthy dip in BP is achievable during short and long duration nap opportunities during simulated night shift work. Our findings support the hypothesis that BP dipping is more common during longer 2-hr versus shorter 30-min naps. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04469803. Registered on 9 July 2020.

Are Short Duration Naps Better than Long Duration Naps for Mitigating Sleep Inertia? Brief Report of a Randomized Crossover Trial of Simulated Night Shift Work.

OBJECTIVE: We sought to test the effects of different duration naps on post-nap cognitive performance during simulated night shifts. METHODS: We used a randomized laboratory-based crossover trial design with simulated 12-hr night shifts and each participant completing three conditions of 72 hrs each (Clinicaltrials.gov; registration # NCT04469803). The three conditions tested included no-nap, a 30-min nap opportunity, and a 2-hr nap opportunity. Naps occurred at 02:00 hrs. Cognitive performance was assessed with the Brief 3-min Psychomotor Vigilance Test (PVT-B). Four PVT-B measures include: reaction time (RT in milliseconds (ms)), lapses (RT > 355 ms), false starts (reactions before stimulus or RT <100 ms), and speed (1,000/RT). The PVT-B was performed at the start of the simulated night shift (19:00), end of shift (07:00), pre-nap (02:00), and at 0 mins, 10 mins, 20 mins, and 30 mins following the 30-min and 2-hr nap conditions. Simultaneously, participants reported subjective ratings of fatigue and other constructs. RESULTS: Twenty-eight (15 female), mostly certified emergency medical technicians or paramedics, consented to participate. For all three conditions, looking within condition, PVT-B lapse performance at the end of the 12-hr simulated night shift (at 07:00) was poorer compared to shift start (p < 0.05). Performance on PVT-B speed, RT, and false starts were poorer at shift end than shift start for the no-nap and 30-min nap conditions (p < 0.05), but not for the 2-hr nap condition (p > 0.05). Compared to pre-nap measures, performance on the PVT-B assessed at 0 mins post-nap showed significant performance declines for lapses and speed for both the 30-min and 2-hr nap conditions (p < 0.05), but not at 10, 20, or 30 mins post-nap. After waking from the 2-hr on-shift nap opportunity (at 0 mins), participants rated sleepiness, difficulty with concentration, and alertness poorer than pre-nap (p < 0.05). Participants in the 30-min nap condition rated alertness poorer immediately after the nap (at 0 mins) compared to pre-nap (p < 0.05). CONCLUSIONS: While sleep inertia was detectable immediately following short 30-min and long 2-hr nap opportunities during simulated night shift work, deficits in cognitive performance and subjective ratings quickly dissipated and were not detectable at 10-30 mins post-nap.

The Beginning of the AI-Enabled Preventative PAP Therapy Era: A First-in-Human Proof of Concept Interventional Study.

Positive Airway Pressure (PAP) therapy is the most common and efficacious treatment for Obstructive Sleep Apnea (OSA). However, it suffers from poor patient adherence due to discomfort and may not fully alleviate all adverse consequences of OSA. Identifying abnormal respiratory events before they have occurred may allow for improved management of PAP levels, leading to improved adherence and better patient outcomes. Our previous work has resulted in the successful development of a Machine-Learning (ML) algorithm for the prediction of future apneic events using existing airflow and air pressure sensors available internally to PAP devices. Although researchers have studied the use of ML for the prediction of apneas, research to date has focused primarily on using external polysomnography sensors that add to patient discomfort and has not investigated the use of internal-to-PAP sensors such as air pressure and airflow to predict and prevent respiratory events. We hypothesized that by using our predictive software, OSA events could be proactively prevented while maintaining patients' sleep quality. An intervention protocol was developed and applied to all patients to prevent OSA events. Although the protocol's cool-down period limited the number of prevention attempts, analysis of 11 participants revealed that our system improved many sleep parameters, which included a statistically significant 31.6% reduction in Apnea-Hypopnea Index, while maintaining sleep quality. Most importantly, our findings indicate the feasibility of unobtrusive identification and unique prevention of each respiratory event as well as paving the path to future truly personalized PAP therapy by further training of ML models on individual patients.

Short-term structural and functional changes after airway clearance therapy in cystic fibrosis.

BACKGROUND: Airway clearance therapy (ACT) with a high-frequency chest wall oscillation (HFCWO) vest is a common but time-consuming treatment. Its benefit to quality of life for cystic fibrosis (CF) patients is well established but has been questioned recently as new highly-effective modulator therapies begin to change the treatment landscape. 129Xe ventilation MRI has been shown to be very sensitive to lung obstruction in mild CF disease, making it an ideal tool to identify and quantify subtle, regional changes. METHODS: 20 CF patients (ages 20.7 ± 5.1 years) refrained from performing ACT before arriving for a single-day visit. Multiple-breath washout (MBW), spirometry, Xe MRI, and ultrashort echo-time (UTE) MRI were obtained twice-before and after patients performed ACT using their prescribed HFCWO vests (average 4.7 ± 0.5 h). UTE MRIs were scored for structural abnormalities, and standard functional metrics were obtained from MBW, spirometry, and Xe MRI-FEV1,pp, LCI2.5, and VDPN4, respectively. RESULTS: Spirometry and Xe MRI detected significant improvements in lung function post-ACT. 15/20 patients showed improvements from a baseline median of 92% FEV1,pp. Similarly, 16/20 patients showed improvements in Xe MRI from a baseline median of 15.2% VDPN4. Average individual changes were +2.6% in FEV1,pp and -1.3% in VDPN4, but without spatial correlations to easily-identifiable causative structural defects (e.g. mucus plugs or bronchiectasis) on UTE MRI. CONCLUSIONS: Lung function improved after a single instance of HFCWO-vest ACT and was detectable by spirometry and Xe MRI. The only common structural abnormalities were mucus plugs, which corresponded to ventilation defects, but ventilation defects were often present without visible abnormalities.

High Frequency-Low Amplitude Oscillometry: Continuous Unobtrusive Monitoring of Respiratory Function on PAP Machines.

Oscillometry or Forced Oscillation Technique, traditionally used in intermittent clinical measurements, has recently gained substantial attention from its application as a continuous monitoring tool for large and small airways. However, low frequency (<8 Hz) continuous oscillometry faces high breathing noise, and hence requires high oscillation amplitudes to maintain an acceptable signal-to-noise ratio. Therefore, PAP machines that utilize low frequency oscillometry do so intermittently to distinguish airway patency several seconds after a breathing pause has occurred. We hypothesized that high frequency and low amplitude (HFLA) oscillometry may be as sensitive and applicable for monitoring upper airway patency to distinguish between central and obstructive apnea and hypopnea events, and for monitoring respiratory impedance. An inline oscillometry prototype device was developed and connected to commercial PAP machines to test whether oscillometry at 17, 43, and 79 Hz are as sensitive to airway patency as oscillometry at 4 Hz. Analysis of 11 patients with 171 apneas and hypopneas showed that all frequency oscillometry inputs were equally sensitive in distinguishing between central and obstructive apneas, while 17 Hz and 43 Hz oscillometry were most sensitive in distinguishing between central and obstructive hypopneas. Observations during normal breathing also showed the same periodicity and cross-correlation between impedance measurements from HFLA oscillometry compared to 4 Hz. Our findings provide an unobtrusive means of distinguishing airway patency during sleep and a means of continuous monitoring of respiratory function, with the potential for detection and prediction of developing respiratory diseases and significantly richer context for data analytics.

Hyperpolarized 129Xenon MRI Ventilation Defect Quantification via Thresholding and Linear Binning in Multiple Pulmonary Diseases.

RATIONALE: There is no agreed upon method for quantifying ventilation defect percentage (VDP) with high sensitivity and specificity from hyperpolarized (HP) gas ventilation MR images in multiple pulmonary diseases for both pediatrics and adults, yet identifying such methods will be necessary for future multi-site trials. Most HP gas MRI ventilation research focuses on a specific pulmonary disease and utilizes one quantification scheme for determining VDP. Here we sought to determine the potential of different methods for quantifying VDP from HP 129Xe images in multiple pulmonary diseases through comparison of the most utilized quantification schemes: linear binning and thresholding. MATERIALS AND METHODS: HP 129Xe MRI was performed in a total of 176 subjects (125 pediatrics and 51 adults, age 20.98±16.48 years) who were either healthy controls (n = 23) or clinically diagnosed with cystic fibrosis (CF) (n = 37), lymphangioleiomyomatosis (LAM) (n = 29), asthma (n = 22), systemic juvenile idiopathic arthritis (sJIA) (n = 11), interstitial lung disease (ILD) (n = 7), or were bone marrow transplant (BMT) recipients (n = 47). HP 129Xe ventilation images were acquired during a ≤16 second breath-hold using a 2D multi-slice gradient echo sequence on a 3T Philips scanner (TR/TE 8.0/4.0ms, FA 10-12°, FOV 300 × 300mm, voxel size≈3 × 3 × 15mm). Images were analyzed using 5 different methods to quantify VDPs: linear binning (histogram normalization with binning into 6 clusters) following either linear or a variant of a nonparametric nonuniform intensity normalization algorithm (N4ITK) bias-field correction, thresholding ≤60% of the mean signal intensity with linear bias-field correction, and thresholding ≤60% and ≤75% of the mean signal intensity following N4ITK bias-field correction. Spirometry was successfully obtained in 84% of subjects. RESULTS: All quantification schemes were able to label visually identifiable ventilation defects in similar regions within all subjects. The VDPs of control subjects were significantly lower (p<0.05) compared to BMT, CF, LAM, and ILD subjects for most of the quantification methods. No one quantification scheme was better able to differentiate individual disease groups from the control group. Advanced statistical modeling of the VDP quantification schemes revealed that in comparing controls to the combined disease group, N4ITK bias-field corrected 60% thresholding had the highest predictive efficacy, sensitivity, and specificity at the VDP cut-point of 2.3%. However, compared to the thresholding quantification schemes, linear binning was able to capture and label subtle low-ventilation regions in subjects with milder obstruction, such as subjects with asthma. CONCLUSION: The difference in VDP between healthy controls and patients varied between the different disease states for all quantification methods. Although N4ITK bias-field corrected 60% thresholding was superior in separating the combined diseased group from controls, linear binning is able to better label low-ventilation regions unlike the current, 60% thresholding scheme. For future clinical trials, a consensus will need to be reached on which VDP scheme to utilize, as there are subtle advantages for each for specific disease.

Characterization of Secondary Bacterial Infections and Antibiotic Use in Mechanically Ventilated Patients With COVID-19 Induced Acute Respiratory Distress Syndrome.

BACKGROUND: COVID-19 has a widely variable clinical syndrome that is difficult to distinguish from bacterial sepsis, leading to high rates of antibiotic use. Early studies indicate low rates of secondary bacterial infections (SBIs) but have included heterogeneous patient populations. Here, we catalogue all SBIs and antibiotic prescription practices in a population of mechanically ventilated patients with COVID-19 induced acute respiratory distress syndrome (ARDS). METHODS: This was a retrospective cohort study of all patients with COVID-19 ARDS requiring mechanical ventilation from 3 Seattle, Washington hospitals in 2020. Data were obtained via electronic and manual review of the electronic medical record. We report the incidence and site of SBIs, mortality, and antibiotics per day using descriptive statistics. RESULTS: We identified 126 patients with COVID-19 induced ARDS during the study period. Of these patients, 61% developed clinical infection confirmed by bacterial culture. Ventilator associated pneumonia was confirmed in 55% of patients, bacteremia in 20%, and urinary tract infection (UTI) in 17%. Staphylococcus aureus was the most commonly isolated bacterial species. A total of 97% of patients received antibiotics during their hospitalization, and patients received nearly one antibiotic per day during their hospital stay. CONCLUSIONS: Mechanically ventilated patients with COVID-19 induced ARDS are at high risk for secondary bacterial infections and have extensive antibiotic exposure.

The negative impact of smartphone usage on nursing students: An integrative literature review.

BACKGROUND: Smartphones are ubiquitous, and for some, an indispensable companion. In nursing education curricula and clinical healthcare settings, smartphones have the potential to augment student learning. Nursing students report significant benefits to smartphone use, which extend beyond learning, to include enhanced communication, clinical decision making and evidence-based practice. Despite these benefits, little is known about the negative impact of smartphones on student learning. OBJECTIVES: This integrative review aimed to synthesise findings from published research that referred to the detrimental direct or indirect effect of smartphone usage on nursing students. DESIGN: The integrative review was guided by the five-stage approach as conceptualised by Whittemore and Knafl (2005). METHODS: Seven electronic databases were systematically searched in consultation with a university librarian (CINAHL Plus, Ovid Medline ALL, Nursing and Allied Health Database, PsycINFO, PubMed, Scopus and ERIC) using a combination of key search terms and medical subject headings. A total of 646 articles were retrieved, and following removal of duplicates, screening of titles and abstracts, a final 27 articles met the inclusion criteria for this review. RESULTS: Studies in the review originated from Korea (n = 7), Turkey (n = 6), India (n = 4), Spain (n = 3), USA (n = 2), Spain/Portugal (n = 1), Iran (n = 1), France (n = 1), Canada (n = 1) and Egypt (n = 1). Personal smartphone use was reported to be a distraction within clinical and classroom learning, and considered as uncivil, and compromised professionalism. Frequently, smartphones were used for entertainment (e.g. social networking) rather than professional purposes. The studies identified a concerning level of nomophobia and smartphone addiction among nursing students that caused stress and anxiety, and adversely affected sleep, learning and academic performance. Recommendations were proposed for smartphone policies. CONCLUSIONS: Excessive smartphones use among nursing students may adversely affect physical and mental health and potentially impact on student learning within the classroom and clinical environment. Educators should consider the implementation of policies or guidance for the responsible use of smartphones by nursing students whilst in the classroom setting and during clinical placement, to mitigate the potential negative impact on health and academic performance.

129Xe MRI as a measure of clinical disease severity for pediatric asthma.

BACKGROUND: Measurement of regional lung ventilation with hyperpolarized 129Xe magnetic resonance imaging (129Xe MRI) in pediatric asthma is poised to advance our understanding of disease mechanisms and pathophysiology in a disorder with diverse clinical phenotypes. 129Xe MRI has not been investigated in a pediatric asthma cohort. OBJECTIVE: We hypothesized that 129Xe MRI is feasible and can demonstrate ventilation defects that relate to and predict clinical severity in a pediatric asthma cohort. METHODS: Thirty-seven children (13 with severe asthma, 8 with mild/moderate asthma, 16 age-matched healthy controls) aged 6 to 17 years old were imaged with 129Xe MRI. Ventilation defect percentage (VDP) and image reader score were calculated and compared with clinical measures at baseline and at follow-up. RESULTS: Children with asthma had higher VDP (P = .002) and number of defects per image slice (defects/slice) (P = .0001) than children without asthma. Children with clinically severe asthma had significantly higher VDP and number of defects/slice than healthy controls. Children with asthma who had a higher number of defects/slice had a higher rate of health care utilization (r = 0.48; P = .03) and oral corticosteroid use (r = 0.43; P = .05) at baseline. Receiver-operating characteristic analysis demonstrated that the VDP and number of defects/slice were predictive of increased health care utilization, asthma, and severe asthma. VDP correlated with FEV1 (r = -0.35; P = .04) and FEV1/forced vital capacity ratio (r = -0.41; P = .01). CONCLUSIONS: 129Xe MRI correlates with asthma severity, health care utilization, and oral corticosteroid use. Because delineation of clinical severity is often difficult in children, 129Xe MRI may be an important biomarker for severity, with potential to identify children at higher risk for exacerbations and improve outcomes.

Sensitive structural and functional measurements and 1-year pulmonary outcomes in pediatric cystic fibrosis.

BACKGROUND: Two functional measurements (multiple breath washout [MBW] and hyperpolarized 129Xe ventilation magnetic resonance imaging [129Xe MRI]) have been shown to be more sensitive to cystic fibrosis (CF) lung obstruction than traditional spirometry. However, functional techniques may be sensitive to different underlying structural abnormalities. The purpose of this study was to determine relationships between these functional markers, their pathophysiology, and 1-year clinical outcomes. METHODS: Spirometry, MBW, 129Xe MRI, and ultrashort echo-time (UTE) MRI were obtained in a same-day assessment of 27 pediatric CF patients (ages 11.5±5.0) who had not begun CFTR modulator therapies. UTE MRI was scored for structural abnormalities and functional metrics obtained via spirometry, MBW and 129Xe MRI. 1-year outcomes (ΔFEV1 and pulmonary exacerbations), during which ≈50% initiated modulator therapy, were obtained from the electronic medical record. RESULTS: MBW, 129Xe MRI, and UTE MRI detected clinically significant disease in more subjects (>78%) compared to spirometry (<30%). UTE MRI suggests increased odds of bronchial changes when mucus plugging is present in the same lobe. MBW and 129Xe MRI correlated best with mucus plugging, while spirometry correlated best with consolidations. Bronchial abnormalities were associated with future pulmonary exacerbations. CONCLUSIONS: MBW, 129Xe MRI, and UTE MRI are more sensitive for detection of pediatric CF lung disease when compared to spirometry. MBW and 129Xe MRI correlated with structural abnormalities which occur in early CF disease, suggesting MBW and 129Xe MRI are valuable tools in mild CF lung disease that can guide clinical decision making.

First year nursing students' perceptions of learning interpersonal communication skills in their paid work: A multi-site Australasian study.

Nursing students are increasingly undertaking paid work while studying and most choose paid work in health care or hospitality. This paper is drawn from a larger sequential exploratory mixed-method study which examined the relationship between students working while studying nursing and the impact on academic performance. In this paper, we explored first year nursing students' perceptions of communication skills gained through paid work. Using a qualitative exploratory design, 50 first year commencing nursing students from four nursing schools (3 Australia; 1 New Zealand) were interviewed. Inductive thematic analysis was used which identified two themes: (i) recognising the value of learning interpersonal communication skills and; (ii)opportunities to develop effective interpersonal communication skills. Paid work provides interpersonal communication skills; active listening, being present and interacting while multi-tasking and emotion management. Undergraduate education providers need to recognise the benefits of paid work for students, including enhancing interpersonal skills.

Whole Genome Sequencing of Peruvian Klebsiella pneumoniae Identifies Novel Plasmid Vectors Bearing Carbapenem Resistance Gene NDM-1.

BACKGROUND: Klebsiella pneumoniae is a bacterial pathogen with increasing rates of resistance to carbapenem antibiotics, but the population structure and genetic drivers of carbapenem-resistant K pneumoniae (CRKP) remain underexplored in developing countries. Carbapenem-resistant K pneumoniae were recently introduced into Peru but have grown rapidly in prevalence, enabling study of this pathogen as it expands into an unaffected environment. METHODS: In this study, using whole genome sequencing, we show that 3 distinct lineages encompass almost all CRKP identified in the hospital where it was first reported in Peru. RESULTS: The most prevalent lineage, ST348, has not been described outside of Europe, raising concern for global dissemination. We identified metallo- ß -lactamase NDM-1 as the primary carbapenem resistance effector, which was harbored on a novel vector resulting from recombination between 2 different plasmids, pKP1-NDM-1 and pMS7884A. CONCLUSIONS: This study is the first of its kind performed in Peru, and it furthers our understanding of the landscape of CRKP infections in Latin America.

Structural lung abnormalities on computed tomography correlate with asthma inflammation in bronchoscopic alveolar lavage fluid.

Objective: Image scoring systems have been developed to assess the severity of specific lung abnormalities in patients diagnosed with various pulmonary diseases except for asthma. A comprehensive asthma imaging scoring system may identify specific abnormalities potentially linking these to inflammatory phenotypes.Methods: Computed tomography (CT) images of 88 children with asthma (50 M/38 F, mean age 7.8 ± 5.4 years) acquired within 12 months of bronchoscopic alveolar lavage fluid (BALF) sampling that assessed airway inflammation cell types were reviewed along with CT images of 49 controls (27 M/22 F, mean age 3.4 ± 2.2 years). Images were scored using a comprehensive scoring system to quantify bronchiectasis (BR), bronchial wall thickening (BWT), ground glass opacity, mucus plugging (MP), consolidations, linear densities (LD), and air trapping (AT). Each category was scored 0-2 in each of six lobar regions (with lingula separated from left upper lobe).Results: Absolute average overall scores of the controls and children with asthma were 0.72 ± 1.59 and 5.39 ± 5.83, respectively (P < 0.0001). Children with asthma scored significantly higher for BR (N = 20, 0.33 ± 0.80, P = 0.0002), BWT (N = 28, 0.72 ± 1.40, P < 0.0001), MP (N = 28, 0.37 ± 1.12, P = 0.0052), consolidation (N = 31, 0.67 ± 1.22, P < 0.0001), LD (N = 58, 1.12 ± 1.44, P < 0.0001), and AT (N = 52, 1.78 ± 2.31, P < 0.0001). There was a significant difference between the BR score of children with positive inflammatory response in BALF (N = 53) and those who were negative for airway inflammation cells (0.14 ± 0.36, P = 0.040).Conclusions: Significant lung structural abnormalities were readily identified on CT of children with asthma, with image differentiation of those with an inflammatory response on BALF. Chest imaging demonstrates potential as a noninvasive clinical tool for additional characterization of asthma phenotypes.