Time-series analysis of satellite-derived fine particulate matter pollution and asthma morbidity in Jackson, MS.

In order to examine associations between asthma morbidity and local ambient air pollution in an area with relatively low levels of pollution, we conducted a time-series analysis of asthma hospital admissions and fine particulate matter pollution (PM2.5) in and around Jackson, MS, for the period 2003 to 2011. Daily patient-level records were obtained from the Mississippi State Department of Health (MSDH) Asthma Surveillance System. Patient geolocations were aggregated into a grid with 0.1° × 0.1° resolution within the Jackson Metropolitan Statistical Area. Daily PM2.5 concentrations were estimated via machine-learning algorithms with remotely sensed aerosol optical depth and other associated parameters as inputs. Controlling for long-term temporal trends and meteorology, we estimated a 7.2% (95% confidence interval 1.7-13.1%) increase in daily all-age asthma emergency room admissions per 10 µg/m3 increase in the 3-day average of PM2.5 levels (current day and two prior days). Stratified analyses reveal significant associations between asthma and 3-day average PM2.5 for males and blacks. Our results contribute to the current epidemiologic evidence on the association between acute ambient air pollution exposure and asthma morbidity, even in an area characterized by relatively good air quality.

Microcoil-Guided Video-Assisted Thoracoscopic Excision of Nodules Suspicious for Metastasis in Patients With Extra-Thoracic Malignancies.

The purpose of this study is to determine the utility of preoperative CT-guided microcoil localization followed by fluoroscopy guided video-assisted thoracoscopic resection in the diagnosis and management of small peripheral pulmonary nodules in patients with extra-thoracic malignancies. This study is a retrospective analysis of prospectively collected data between August 2003 and September 2013. Fifty patients with extra-thoracic malignancies underwent preoperative localization of small indeterminate pulmonary nodules using CT-guided microcoil localization. Nodules were then resected by video-assisted thoracoscopic resection wedge excision and intraoperative fluoroscopy guidance. Univariate and multivariate logistic regression analysis were conducted. Fifty patients with a history of 14 different extra-thoracic cancers (57% female, mean age 62 years) had 55 nodules resected (mean size = 12 mm, depth from visceral pleura = 22 mm). Histology of resected nodules showed metastasis (25 of 50 patients), benign (10 of 50), and (15 of 50) early stage primary lung cancer. Smokers were found 6 times more likely to present with primary lung cancer than metastasis (P < 0.009). CT-guided microcoil localization procedure was successful in all patients with a mean time of 31(10) minutes and allowed successful wedge resection in all cases with no major complications. The mean operative time and fluoroscopy time were 27(12) minutes and 3(5) minutes, respectively. Microcoil-guided thoracoscopic wedge resection was effective in achieving early definitive diagnosis and changed management in 50% of patients with presumed metastasis with minimal morbidity.

Participant selection for lung cancer screening by risk modelling (the Pan-Canadian Early Detection of Lung Cancer [PanCan] study): a single-arm, prospective study.

BACKGROUND: Results from retrospective studies indicate that selecting individuals for low-dose CT lung cancer screening on the basis of a highly predictive risk model is superior to using criteria similar to those used in the National Lung Screening Trial (NLST; age, pack-year, and smoking quit-time). We designed the Pan-Canadian Early Detection of Lung Cancer (PanCan) study to assess the efficacy of a risk prediction model to select candidates for lung cancer screening, with the aim of determining whether this approach could better detect patients with early, potentially curable, lung cancer. METHODS: We did this single-arm, prospective study in eight centres across Canada. We recruited participants aged 50-75 years, who had smoked at some point in their life (ever-smokers), and who did not have a self-reported history of lung cancer. Participants had at least a 2% 6-year risk of lung cancer as estimated by the PanCan model, a precursor to the validated PLCOm2012 model. Risk variables in the model were age, smoking duration, pack-years, family history of lung cancer, education level, body-mass index, chest x-ray in the past 3 years, and history of chronic obstructive pulmonary disease. Individuals were screened with low-dose CT at baseline (T0), and at 1 (T1) and 4 (T4) years post-baseline. The primary outcome of the study was incidence of lung cancer. This study is registered with ClinicalTrials.gov, number NCT00751660. FINDINGS: 7059 queries came into the study coordinating centre and were screened for PanCan risk. 15 were duplicates, so 7044 participants were considered for enrolment. Between Sept 24, 2008, and Dec 17, 2010, we recruited and enrolled 2537 eligible ever-smokers. After a median follow-up of 5·5 years (IQR 3·2-6·1), 172 lung cancers were diagnosed in 164 individuals (cumulative incidence 0·065 [95% CI 0·055-0·075], incidence rate 138·1 per 10 000 person-years [117·8-160·9]). There were ten interval lung cancers (6% of lung cancers and 6% of individuals with cancer): one diagnosed between T0 and T1, and nine between T1 and T4. Cumulative incidence was significantly higher than that observed in NLST (4·0%; p<0·0001). Compared with 593 (57%) of 1040 lung cancers observed in NLST, 133 (77%) of 172 lung cancers in the PanCan Study were early stage (I or II; p<0·0001). INTERPRETATION: The PanCan model was effective in identifying individuals who were subsequently diagnosed with early, potentially curable, lung cancer. The incidence of cancers detected and the proportion of early stage cancers in the screened population was higher than observed in previous studies. This approach should be considered for adoption in lung cancer screening programmes. FUNDING: Terry Fox Research Institute and Canadian Partnership Against Cancer.

Dalbavancin Use for the Treatment of Methicillin-resistant Staphylococcus aureus Pneumonia.

Dalbavancin is a lipoglycopeptide with a long half-life that allows infrequent dosing. It is indicated for the treatment of acute bacterial skin and skin structure infections caused by susceptible organisms, including Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). Although this agent has been used off-label clinically, there are minimal data in infections outside the current indications. We report a case of a 28-year-old nonadherent male with HIV presenting with pneumonia due to MRSA that was treated with dalbavancin. The patient was admitted to the hospital with classic pneumonia symptoms, and sputum cultures and bronchoalveolar lavage grew MRSA. Other infections were ruled out. The patient was initially treated with vancomycin, but subtherapeutic concentrations prompted a change to dalbavancin upon discharge. The patient was readmitted 11 days later with the complaints of hemoptysis and shortness of breath, with unchanged imaging. However, no evidence of MRSA was found at this time. Utility of dalbavancin for other disease states has profound implications, particularly in patients with poor medication adherence.

Remembering Dr. Frederick Griffith Pearson.

SUMMARY: Canada has lost a remarkable surgeon and leader. Dr. Frederick Griffith "Griff" Pearson, aged 90, died in Kitchener, Ont., on Aug. 10, 2016, surrounded by his wife, Hilppa Pearson, and his family.

Acute bacterial skin and skin structure infections (ABSSSI): practice guidelines for management and care transitions in the emergency department and hospital.

BACKGROUND: Acute bacterial skin and skin structure infections (ABSSSI), formally referred to as complicated skin and soft tissue infections, include infections with resistance to previously effective antimicrobials. Increasing dramatically in incidence, they have become a challenging medical problem associated with high direct and indirect costs to both the medical system and society. OBJECTIVES: To describe the burden of ABSSSI and to explore multidisciplinary approaches to its management and new treatments that can be initiated in the emergency department. DISCUSSION: We offer a best practice model aimed at providing risk-stratified and convenient care for ABSSSI at the lowest possible cost, while minimizing complications, readmissions, and inappropriate antibiotic use. In doing so, we focus on the care provided by emergency physicians and hospitalists and the transition of management between them for inpatient care, as well as the facilitation of observation or direct-to-outpatient care for suitable patients. CONCLUSIONS: A standard, consistent, and multidisciplinary approach to ABSSSI can streamline care, reduce admissions, support antimicrobial stewardship, and improve clinical and resource consumption outcomes.

Preoperative computed tomography-guided microcoil localization of small peripheral pulmonary nodules: a prospective randomized controlled trial.

OBJECTIVES: Growing, small, peripheral, pulmonary nodules in patients at high risk for lung cancer lead to requests for video-assisted thoracoscopic (VATS) resection for pathologic diagnosis. The purpose of this randomized controlled trial was to determine if preoperative localization using percutaneously placed computed tomography (CT)-guided platinum microcoils decreases the need for thoracotomy or VATS anatomic resection (segmentectomy/lobectomy) for diagnosis. METHODS: Patients with undiagnosed nodules of 15 mm or less were randomized to either no localization or preoperative microcoil localization. Coils were placed with the distal end deep to the nodule and the superficial end coiled on the visceral pleural surface with subsequent visualization by intraoperative fluoroscopy and VATS. Nodules were removed by VATS wedge excision using endostaplers. The primary outcome was a VATS wedge excision for pathologic diagnosis of the nodule without the need for either thoracotomy or VATS anatomic resection. RESULTS: Sixty patients were randomized and 56 underwent surgery between March 2010 and June 2012. Twenty-nine underwent microcoil localization and 27 did not. The baseline characteristics (age, sex, forced expiratory volume in the first second of expiration, nodule size/depth) were similar. The coil group had a higher rate of successful diagnosis with VATS wedge resection alone (27/29 vs 13/27; P < .001), decreased operative time to nodule excision (37 ± 39 vs 100 ± 67 minutes; P < .001), and reduced stapler firings (3.7 ± 2.0 vs 5.9 ± 31; P = .003) with no difference in total costs. Pathologic diagnoses included 14 benign nodules, 32 primary lung malignancies, and 10 metastases. There were no clinically significant complications related to the coil placement or wedge resection. CONCLUSIONS: Preoperative CT-guided microcoil localization decreases the need for thoracotomy or VATS anatomic resection for the diagnosis of small peripheral pulmonary nodules.

Resource utilization and costs during the initial years of lung cancer screening with computed tomography in Canada.

BACKGROUND: It is estimated that millions of North Americans would qualify for lung cancer screening and that billions of dollars of national health expenditures would be required to support population-based computed tomography lung cancer screening programs. The decision to implement such programs should be informed by data on resource utilization and costs. METHODS: Resource utilization data were collected prospectively from 2059 participants in the Pan-Canadian Early Detection of Lung Cancer Study using low-dose computed tomography (LDCT). Participants who had 2% or greater lung cancer risk over 3 years using a risk prediction tool were recruited from seven major cities across Canada. A cost analysis was conducted from the Canadian public payer's perspective for resources that were used for the screening and treatment of lung cancer in the initial years of the study. RESULTS: The average per-person cost for screening individuals with LDCT was $453 (95% confidence interval [CI], $400-$505) for the initial 18-months of screening following a baseline scan. The screening costs were highly dependent on the detected lung nodule size, presence of cancer, screening intervention, and the screening center. The mean per-person cost of treating lung cancer with curative surgery was $33,344 (95% CI, $31,553-$34,935) over 2 years. This was lower than the cost of treating advanced-stage lung cancer with chemotherapy, radiotherapy, or supportive care alone, ($47,792; 95% CI, $43,254-$52,200; p = 0.061). CONCLUSION: In the Pan-Canadian study, the average cost to screen individuals with a high risk for developing lung cancer using LDCT and the average initial cost of curative intent treatment were lower than the average per-person cost of treating advanced stage lung cancer which infrequently results in a cure.

Validation of airway wall measurements by optical coherence tomography in porcine airways.

Examining and quantifying changes in airway morphology is critical for studying longitudinal pathogenesis and interventions in diseases such as chronic obstructive pulmonary disease and asthma. Here we present fiber-optic optical coherence tomography (OCT) as a nondestructive technique to precisely and accurately measure the 2-dimensional cross-sectional areas of airway wall substructure divided into the mucosa (WAmuc), submucosa (WAsub), cartilage (WAcart), and the airway total wall area (WAt). Porcine lung airway specimens were dissected from freshly resected lung lobes (N = 10). Three-dimensional OCT imaging using a fiber-optic rotary-pullback probe was performed immediately on airways greater than 0.9 mm in diameter on the fresh airway specimens and subsequently on the same specimens post-formalin-fixation. The fixed specimens were serially sectioned and stained with H&E. OCT images carefully matched to selected sections stained with Movat's pentachrome demonstrated that OCT effectively identifies airway epithelium, lamina propria, and cartilage. Selected H&E sections were digitally scanned and airway total wall areas were measured. Traced measurements of WAmuc, WAsub, WAcart, and WAt from OCT images of fresh specimens by two independent observers found there were no significant differences (p>0.05) between the observer's measurements. The same wall area measurements from OCT images of formalin-fixed specimens found no significant differences for WAsub, WAcart and WAt, and a small but significant difference for WAmuc. Bland-Altman analysis indicated there were negligible biases between the observers for OCT wall area measurements in both fresh and formalin-fixed specimens. Bland-Altman analysis also indicated there was negligible bias between histology and OCT wall area measurements for both fresh and formalin-fixed specimens. We believe this study sets the groundwork for quantitatively monitoring pathogenesis and interventions in the airways using OCT.

Daptomycin-induced rhabdomyolysis and acute liver injury.

Daptomycin use is a known cause of rhabdomyolysis; its role in liver injury is less certain. We report a case of daptomycin-induced rhabdomyolysis with liver injury. This report indicates a role for liver function monitoring while receiving daptomycin, as well as the importance of promptly considering drug toxicities in acute and emergency care settings.

Expression of matrix metalloproteinase-1 in alveolar macrophages, type II pneumocytes, and airways in smokers: relationship to lung function and emphysema.

BACKGROUND: An imbalance between proteolytic enzymes and their inhibitors is thought to be involved in the pathogenesis of chronic obstructive pulmonary disease. Matrix metalloproteinase-1, also known as interstitial collagenase, has been implicated as a potentially important proteinase in the genesis of chronic obstructive pulmonary disease and, more specifically, emphysema. METHODS: We performed quantitative immunohistochemical assessment of matrix metalloproteinase-1 expression in the resected lung of 20 smokers/ex-smokers who had varying severity of airflow obstruction and emphysema and compared this with the lungs of 5 nonsmokers. Emphysema was measured using a morphometric measure of the lungs' surface area/volume ratio and with qualitative and quantitative computed tomography (CT) measures of emphysema. RESULTS: There were significantly more matrix metalloproteinase-1-expressing alveolar macrophages and type II pneumocytes as well as a greater percentage of small airways that stained positively for matrix metalloproteinase-1 in the lungs of smokers than in those of nonsmokers (p < 0.0001, p < 0.0001, and p = 0.0003, respectively). The extent of staining of type II pneumocytes and airways for matrix metalloproteinase-1 was significantly related to the extent of smoking (p = 0.012 and p = 0.013, respectively). In addition, the extent of matrix metalloproteinase-1 staining of alveolar macrophages was related to the lung surface area/volume ratio and to qualitative estimates of emphysema on CT. CONCLUSION: These findings suggest that cigarette smoking increases expression of matrix metalloproteinase-1 in alveolar macrophages as well as in alveolar and small airway epithelial cells. Smokers who develop emphysema have increased alveolar macrophage expression of matrix metalloproteinase-1.

Alveolar macrophage proteinase/antiproteinase expression in lung function and emphysema.

Alveolar macrophages play an important role in chronic obstructive pulmonary disease via production of matrix metalloproteinases (MMPs) and cathepsins as well as their inhibitors, tissue inhibitors of metalloproteinases and cystatin C. We hypothesised that expression levels of these molecules by alveolar macrophages at baseline and after stimulation would be influenced by genotype and associated with chronic obstructive pulmonary disease phenotypes. Quantitative PCR and ELISAs/gelatine zymography were used to investigate expression levels of mRNA and protein, respectively. The relationships of expression with genotype, pulmonary function and emphysema were analysed. The results showed that basal expression level of MMP12 mRNA was inversely related to the diffusing capacity of the lung for carbon monoxide/alveolar volume and to forced expiratory volume in 1 s/forced vital capacity after correction for multiple comparisons. The expression level of MMP12 protein stimulated with lipopolysaccharide was also inversely related to the diffusing capacity of the lung for carbon monoxide/alveolar volume and was positively related to the extent of emphysema. The basal expression of MMP1 mRNA was positively correlated with the extent of emphysema. Cathepsin L protein level was positively associated with forced expiratory volume in 1 s % predicted. We conclude that increased MMP12 and MMP1 expression may play a role in the pathogenesis of emphysema. Cathepsin L and MMP9 may be involved in the development of airflow limitation.

GeoMedStat: an integrated spatial surveillance system to track air pollution and associated healthcare events.

Air pollutants, such as particulate matter with a diameter ≤2.5 microns (PM2.5) and ozone (O3), are known to exacerbate asthma and other respiratory diseases. An integrated surveillance system that tracks such air pollutants and associated disease incidence can assist in risk assessment, healthcare preparedness and public awareness. However, the implementation of such an integrated environmental health surveillance system is a challenge due to the disparate sources of many types of data and the implementation becomes even more complicated for a spatial and real-time system due to lack of standardised technological components and data incompatibility. In addition, accessing and utilising health data that are considered as Protected Health Information (PHI) require maintaining stringent protocols, which have to be supported by the system. This paper aims to illustrate the development of a spatial surveillance system (GeoMedStat) that is capable of tracking daily environmental pollutants along with both daily and historical patient encounter data. It utilises satellite data and the groundmonitor data from the US National Aeronautics and Space Administration (NASA) and the US Environemental Protection Agenecy (EPA), rspectively as inputs estimating air pollutants and is linked to hospital information systems for accessing chief complaints and disease classification codes. The components, developmental methods, functionality of GeoMedStat and its use as a real-time environmental health surveillance system for asthma and other respiratory syndromes in connection with with PM2.5 and ozone are described. It is expected that the framework presented will serve as an example to others developing real-time spatial surveillance systems for pollutants and hospital visits.

Probability of cancer in pulmonary nodules detected on first screening CT.

BACKGROUND: Major issues in the implementation of screening for lung cancer by means of low-dose computed tomography (CT) are the definition of a positive result and the management of lung nodules detected on the scans. We conducted a population-based prospective study to determine factors predicting the probability that lung nodules detected on the first screening low-dose CT scans are malignant or will be found to be malignant on follow-up. METHODS: We analyzed data from two cohorts of participants undergoing low-dose CT screening. The development data set included participants in the Pan-Canadian Early Detection of Lung Cancer Study (PanCan). The validation data set included participants involved in chemoprevention trials at the British Columbia Cancer Agency (BCCA), sponsored by the U.S. National Cancer Institute. The final outcomes of all nodules of any size that were detected on baseline low-dose CT scans were tracked. Parsimonious and fuller multivariable logistic-regression models were prepared to estimate the probability of lung cancer. RESULTS: In the PanCan data set, 1871 persons had 7008 nodules, of which 102 were malignant, and in the BCCA data set, 1090 persons had 5021 nodules, of which 42 were malignant. Among persons with nodules, the rates of cancer in the two data sets were 5.5% and 3.7%, respectively. Predictors of cancer in the model included older age, female sex, family history of lung cancer, emphysema, larger nodule size, location of the nodule in the upper lobe, part-solid nodule type, lower nodule count, and spiculation. Our final parsimonious and full models showed excellent discrimination and calibration, with areas under the receiver-operating-characteristic curve of more than 0.90, even for nodules that were 10 mm or smaller in the validation set. CONCLUSIONS: Predictive tools based on patient and nodule characteristics can be used to accurately estimate the probability that lung nodules detected on baseline screening low-dose CT scans are malignant. (Funded by the Terry Fox Research Institute and others; ClinicalTrials.gov number, NCT00751660.).

The use of thoracoscopy to enhance medical students' interest and understanding of thoracic anatomy.

AIM: To develop a video-based educational tool designed for teaching thoracic anatomy and to examine whether this tool would increase students' stimulation and motivation for learning anatomy. METHODS: Our video-based tool was developed by recording different thoracoscopic procedures focusing on intraoperative live thoracic anatomy. The tool was then integrated into a pre-existing program for first year medical students (n = 150), and included cadaver dissection of the thorax and review of clinical problem scenarios of the respiratory system. Students were guided through a viewing of the videotape that demonstrated live anatomy of the thorax (15 minutes) and then asked to complete a 5-point Likert-type questionnaire assessing the video's usefulness. Apart from this, a small group of entirely different set of students was divided into two groups, one group to view the 15-minute video presentation of thoracoscopy and chest anatomy and the other group to attend a 15-minute lecture of chest anatomy using radiological images. Both groups took a 10-item pretest and post-test multiple choice questions examination to assess short-term knowledge gained. RESULTS: Of 150 medical students, 119 completed the questionnaires, 88.6% were satisfied with the thoracoscopic video as a teaching tool, 86.4% were satisfied with the quality of the images, 69.2% perceived it to be beneficial in learning anatomy, 96.2% increased their interest in learning anatomy, and 88.5% wanted this new teaching tool to be implemented to the curriculum. Majority (80.7%) of the students increased their interest in surgery as a future career. Post-test scores were significantly higher in the thoracoscopy group (P = 0.0175). CONCLUSION: Incorporating live surgery using thoracoscopic video presentation in the gross anatomy teaching curriculum had high acceptance and satisfaction scores from first year medical students. The video increased students' interest in learning, in clinically applying anatomic fact, and in surgery as a future career.