Culture-independent Multilocus sequence typing screening for Haemophilus influenzae cross-infection in non-cystic fibrosis bronchiectasis.

Whether cross-infection of respiratory pathogens between patients with non-cystic fibrosis bronchiectasis occurs is debated. Investigation with traditional microbiological culture risks simplifying the lung microbiome. We demonstrate the use of culture-independent Multilocus sequence typing to screen for Haemophilus influenzae strain types in a cohort of twenty-eight patients with non-cystic fibrosis bronchiectasis.

Long-term safety and efficacy of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis and at least one F508del allele: 144-week interim results from a 192-week open-label extension study.

BACKGROUND: In two pivotal phase 3 trials, up to 24 weeks of treatment with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was efficacious and safe in patients with cystic fibrosis (CF) ≥12 years of age who have at least one F508del allele. The aim of this study is to assess long-term safety and efficacy of ELX/TEZ/IVA in these patients. METHODS: In this phase 3, open-label, single-arm extension study, participants with F508del-minimal function (from a 24-week parent study; n=399) or F508del-F508del (from a 4-week parent study; n=107) genotypes receive ELX/TEZ/IVA at the same dose (ELX 200 mg once daily, TEZ 100 mg once daily and IVA 150 mg every 12 h). The primary end-point is safety and tolerability. A prespecified interim analysis was conducted when the last participant reached the Week 144 visit. RESULTS: At the Week 144 interim analysis, mean duration of exposure to ELX/TEZ/IVA in the extension study was 151.1 weeks. Exposure-adjusted rates of adverse events (AEs) (586.6 events per 100 participant-years) and serious AEs (22.4 events per 100 participant-years) were lower than in the ELX/TEZ/IVA treatment group in the 24-week parent study (1096.0 and 36.9 events per 100 participant-years, respectively); most participants had AEs classified as mild (16.4% of participants) or moderate (60.3% of participants) in severity. 14 participants (2.8%) had AEs that led to treatment discontinuation. Following initiation of ELX/TEZ/IVA, participants had increases in forced expiratory volume in 1 s (FEV1) percentage predicted, Cystic Fibrosis Questionnaire-Revised respiratory domain score and body mass index, and had decreases in sweat chloride concentration and pulmonary exacerbation rates that were maintained over the interim analysis period. The mean annualised rate of change in FEV1 % pred was +0.07 (95% CI -0.12-0.26) percentage points among the participants. CONCLUSIONS: ELX/TEZ/IVA was generally safe and well tolerated, with a safety profile consistent with the 24-week parent study. Participants had sustained improvements in lung function, respiratory symptoms, CF transmembrane conductance regulator function, pulmonary exacerbation rates and nutritional status. These results support the favourable safety profile and durable, disease-modifying clinical benefits of ELX/TEZ/IVA.

Culture-independent multilocus sequence typing of Pseudomonas aeruginosa for cross-infection screening.

The genotyping of pathogens within cystic fibrosis cohorts is an important process, enabling the detection of transmissible and clinically-important strains. Traditionally this has been via culture-dependent processes. However, culture-independent investigation of respiratory samples is becoming more common, with such approaches highlighting the limitations of culture-based methods. In this study we describe the culture-independent application of multilocus sequence typing (MLST) for Pseudomonas aeruginosa, performed on DNA extracted from the sputa of cystic fibrosis patients. We compare the output to conventional culture-dependent MLST applied to the same samples and demonstrate high concordance. Culture-independent MLST enabled genotyping of culture-negative samples in patients from whom P. aeruginosa was intermittently isolated, and revealed the hidden presence of transmissible strains. Culture-independent MLST is also capable of highlighting samples containing multiple strains, albeit inconsistently. We conclude that culture-independent MLST can be a useful genotyping tool for screening cohorts and identifying patients that warrant further detailed investigation.

The Value of Live Tissue Training for Combat Casualty Care: A Survey of Canadian Combat Medics With Battlefield Experience in Afghanistan.

INTRODUCTION: The optimum method for training military personnel for combat casualty care is unknown. In particular, there is debate regarding the incremental benefit of live animal tissue training (LTT) over inanimate human patient simulators (HPSs). Although both LTT and HPS are currently used for predeployment training, the efficacy of these models has not been established. MATERIALS AND METHODS: Canadian Armed Forces combat medics, deployed to Afghanistan between 2006 and 2011, were surveyed retrospectively regarding their experience with combat casualty care and predeployment training. HPSs were used to prepare these combat medics for early rotations. In later years, personnel received a combination of training modalities including HPS and LTT, using anaesthetized porcine models in accordance with appropriate animal care standards. Among those deployed on multiple rotations, there was a cohort who was prepared for deployment using only HPS training, and who later were prepared using mixed-modality training, which included LTT. We asked these medics to compare their predeployment training using HPS only versus their mixed-modality training in how each training package prepared them for battlefield trauma care. RESULTS: Thirty-eight individuals responded, with 20 respondents deployed on multiple rotations. Respondents performed life-saving skills during 89% of the rotations. Self-perceived competence and preparedness were notably higher after incorporation of LTT than after HPS alone. Of 17 respondents deployed on both early and late rotations, the majority felt the latter training was more worthwhile. In addition, almost all individuals felt that LTT should be added to HPS training. Narrative comments described multiple benefits of adding LTT to other types of training. CONCLUSIONS: Among many experienced Canadian Armed Forces personnel, LTT is considered essential predeployment preparation. Individuals who experienced only HPS training before active duty on their first combat deployment reported feeling more competent on subsequent combat deployments after the addition of live tissue models. IMPACT: There has been a movement away from the use of LTT in preparing combat medics for deployment. This article suggests that we should reconsider any decision to completely exclude Live Tissue Training as part of our training plan for combat medics. RECOMMENDATIONS: Military medical organizations should consider judiciously incorporating LTT with human patient simulation training to prepare combat medics for treating battlefield trauma.

Molecular epidemiology of Pseudomonas aeruginosa in an unsegregated bronchiectasis cohort sharing hospital facilities with a cystic fibrosis cohort.

While Pseudomonas aeruginosa (PA) cross-infection is well documented among patients with cystic fibrosis (CF), the equivalent risk among patients with non-CF bronchiectasis (NCFB) is unclear, particularly those managed alongside patients with CF. We performed analysis of PA within a single centre that manages an unsegregated NCFB cohort alongside a segregated CF cohort. We found no evidence of cross-infection between the two cohorts or within the segregated CF cohort. However, within the unsegregated NCFB cohort, evidence of cross-infection was found between three (of 46) patients. While we do not presently advocate any change in the management of our NCFB cohort, longitudinal surveillance is clearly warranted.

Tactical combat casualty care in the Canadian Forces: lessons learned from the Afghan war.

Tactical Combat Casualty Care (TCCC) is intended to treat potentially preventable causes of death on the battlefield, but acknowledges that application of these treatments may place the provider and even the mission in jeopardy if performed at the wrong time. Therefore, TCCC classifies the tactical situation with respect to health care provision into 3 phases (care under fire, tactical field care and tactical evacuation) and only permits certain interventions to be performed in specific phases based on the danger to the provider and casualty. In the 6 years that the Canadian Forces (CF) have been involved in sustained combat operations in Kandahar, Afghanistan, more than 1000 CF members have been injured and more than 150 have been killed. As a result, the CF gained substantial experience delivering TCCC to wounded soldiers on the battlefield. The purpose of this paper is to review the principles of TCCC and some of the lessons learned about battlefield trauma care during this conflict.

Spinal injuries after improvised explosive device incidents: implications for Tactical Combat Casualty Care.

BACKGROUND: Tactical Combat Casualty Care aims to treat preventable causes of death on the battlefield but deemphasizes the importance of spinal immobilization in the prehospital tactical setting. However, improvised explosive devices (IEDs) now cause the majority of injuries to Canadian Forces (CF) members serving in Afghanistan. We hypothesize that IEDs are more frequently associated with spinal injuries than non-IED injuries and that spinal precautions are not being routinely employed on the battlefield. METHODS: We examined retrospectively a database of all CF soldiers who were wounded and arrived alive at the Role 3 Multinational Medical Unit in Kandahar, Afghanistan, from February 7, 2006, to October 14, 2009. We collected data on demographics, injury mechanism, anatomic injury descriptions, physiologic data on presentation, and prehospital interventions performed. Outcomes were incidence of any spinal injuries. RESULTS: Three hundred seventy-two CF soldiers were injured during the study period and met study criteria. Twenty-nine (8%) had spinal fractures identified. Of these, 41% (n = 12) were unstable, 31% (n = 9) stable, and 28% indeterminate. Most patients were injured by IEDs (n = 212, 57%). Patients injured by IEDs were more likely to have spinal injuries than those injured by non-IED-related mechanisms (10.4% vs. 2.3%; p < 0.01). IED victims were even more likely to have spinal injuries than patients suffering blunt trauma (10.4% vs. 6.7%; p = 0.02). Prehospital providers were less likely to immobilize the spine in IED victims compared with blunt trauma patients (10% [22 of 212] vs. 23.0% [17 of 74]; p < 0.05). CONCLUSIONS: IEDs are a common cause of stable and unstable spinal injuries in the Afghanistan conflict. Spinal immobilization is an underutilized intervention in the battlefield care of casualties in the conflict in Afghanistan. This may be a result of tactical limitations; however, current protocols should continue to emphasize the judicious use of immobilization in these patients.

Zinc therapy for night blindness in cystic fibrosis.

This is the first report of a supplemented CF patient presenting with clinical vitamin A deficiency to be successfully treated with zinc therapy alone. Therefore in addition to retinol supplementation, normalizing serum zinc levels may be important in maintaining the vitamin A status of CF patients. The interactions and synergistic effects between the two micronutrients are discussed.

Gas cooking and smoking habits and the risk of childhood and adolescent wheeze.

The authors investigated the risk of wheezing illnesses in relation to contemporaneous pollutant exposures (gas cooking, heating, and smoking) in childhood and adolescence in a cohort of 2,289 United Kingdom subjects. Data from two questionnaires assessing wheezing at ages 7-8 and 15-17 years and one questionnaire on current and past pollutant exposures at age 16-18 years were studied (1987-1996). The 1,868 subjects returning all three questionnaires were divided into three groups representing childhood (10.5%), adolescent (10.9%), and persistent (i.e., both; 16.3%) wheezing and compared with 1,165 controls (62.4%) without wheezing. The estimated risks of childhood wheezing were increased by exposure to any gas in childhood (odds ratio (OR) = 1.47, 95% confidence interval (CI): 1.05, 2.04) and exposure to a gas hob in childhood (OR = 1.56, 95% CI: 1.13, 2.16) and were increased further in those persistently exposed. Risk of persistent wheezing in adolescence was paradoxically reduced by exposure to a gas hob (OR = 0.67, 95% CI: 0.50, 0.91), possibly because of selection avoidance. Contemporaneous exposure to combined smoking by both parents was associated with wheezing in all groups (odds ratios ranged from 1.62 (95% CI: 1.06, 2.46) to 1.93 (95% CI: 1.10, 3.38)). Maternal smoking alone was associated with persistent wheezing and with both childhood (OR = 1.90, 95% CI: 1.06, 3.39) and persistent (OR = 2.18, 95% CI: 1.15, 4.14) wheezing if smoking occurred throughout childhood and adolescence. The authors conclude that exposures to gas cooking and smoking in childhood and adolescence increase the overall risk of wheezing.

Iron deficiency in cystic fibrosis: relationship to lung disease severity and chronic Pseudomonas aeruginosa infection.

BACKGROUND: Iron deficiency (ID) is common in patients with cystic fibrosis (CF) and may be related to GI factors and chronic inflammation. Pseudomonas aeruginosa (PA) infection is predominantly responsible for chronic lung suppuration in patients with CF, but its survival is critically dependent on the availability of extracellular iron, which it obtains via highly efficient mechanisms. OBJECTIVE: To determine whether ID in CF patients is directly related to the severity of suppurative lung disease. DESIGN: We determined the iron status of 30 randomly selected adult CF patients (13 women) and assessed the relationship to lung disease severity and GI factors by determining their daily sputum volume, FEV(1) percent predicted, C-reactive protein (CRP) level, erythrocyte sedimentation rate, and degree of pancreatic supplementation. Additionally, we measured the sputum concentrations of iron and ferritin in a randomly selected subgroup of 13 of the 30 subjects. SETTING: Adult CF Service in a tertiary-care center. RESULTS: Seventy-four percent of subjects experienced ID (ie, serum iron levels < or = 12 micromol/L and/or transferrin saturation levels < or = 16%). There was no relationship found with the degree of pancreatic supplementation. The daily sputum volume was strongly associated with low serum iron levels, transferrin saturation, ferritin/CRP ratio, and FEV(1) percent predicted (p < 0.05). Serum iron levels and transferrin saturation were negatively related to CRP (r = -0.8 and r = -0.7, respectively; p < 0.01) and erythrocyte sedimentation rate (r = -0.5 and r = -0.4, respectively; p < 0.05). FEV(1) percent predicted was positively related to serum iron level (r = 0.5; p < 0.01), transferrin saturation (r = 0.4; p < 0.05), and ferritin/CRP ratio (r = 0.7; p < 0.05). Sputum iron concentration (median, 63 micromol/L; range, 17 to 134 micromol/L) and ferritin concentration (median, 5,038 microg/L; range, 894 to 6,982 microg/L) exceeded plasma levels and negatively correlated with FEV(1) percent predicted (r = -0.6 and r = -0.5, respectively; p < or = 0.05). CONCLUSION: In our CF patients, ID was directly related to the increased severity of suppurative lung disease but not to the degree of pancreatic insufficiency. Iron loss into the airway may contribute to ID and may facilitate PA infection.