A Spatial Analysis of Functional Outcomes and Quality of Life Outcomes After Pediatric Injury

BACKGROUND: Changes in health-related quality of life (HRQoL) are more regularly being monitored during the first year after injury. Monitoring changes in HRQoL using spatial cluster analysis can potentially identify concentrations of geographic areas with injury survivors with similar outcomes, thereby improving how interventions are delivered or in how outcomes are evaluated. METHODS: We used a spatial scan statistic designed for oridinal data to test two different spatial cluster analysis of very low, low, high, and very high HRQoL scores. Our study was based on HRQoL scores returned by children treated for injury at British Columbia Children\u27s Hospital and discharged to the Vancouver Metropolitan Area. Spatial clusters were assessed at 4 time periods - baseline (based on pre-injury health as reported prior to discharge from hospital), and one, four, and twelve months after discharge. Outcome data were measured used the PedsQL™ outcome scale. Outcome values of very low, low, high, and very high HRQoL scores were defined by classifying PedsQL™ scores into quartiles. In the first test, all scores were assessed for clustering without specifying whether the response score was from a baseline or follow-up response. In the second analysis, we built a space-time model to identify whether HRQoL responses could be identified at specific time points. RESULTS: Among all participants, geographic clustering of response scores were observed globally and at specific time periods. In the purely spatial analysis, five significant clusters of \u27very low\u27 PedsQL physical and psychosocial health outcomes were identified within geographic zones ranging in size from 1 to 21 km. A space-time analysis of outcomes identified significant clusters of both \u27very low\u27 and \u27low\u27 outcomes between survey months within zones ranging in size from 3 to 5 km. CONCLUSION: Monitoring patient health outcomes following injury is important for planning and targeting interventions. A common theme in the literature is that future prevention efforts may benefit from identifying those most a risk of developing ongoing problems after injury in effort to target resources to those most in need. Spatial scan statistics are tools that could be applied for identifying concentrations of poor recovery outcomes. By classifying outcomes as a categorical variable, clusters of \u27potentially low\u27 outcomes can also be mapped, thereby identifying populations whose recovery status may decrease

Nontuberculous Mycobacteria in Respiratory Tract Infections, Eastern Asia

To characterize the distribution of nontuberculous mycobacteria (NTM) species isolated from pulmonary samples from persons in Asia and their association with pulmonary infections, we reviewed the literature. Mycobacterium avium complex bacteria were most frequently isolated (13%–81%) and were the most common cause of pulmonary NTM disease (43%–81%). Also pathogenic were rapidly growing mycobacteria (M. chelonae, M. fortuitum, M. abscessus). Among all NTM isolated from pulmonary samples, 31% (582/1,744) were considered clinically relevant according to American Thoracic Society diagnostic criteria. Most patients were male (79%) and had a history of tuberculosis (37%). In Asia, high prevalence of rapidly growing mycobacteria and a history of tuberculosis are distinct characteristics of pulmonary NTM disease. This geographic variation is not well reflected in the American Thoracic Society criteria for NTM infections and could be incorporated in future guidelines

All-cause admissions following a first-ever exacerbation-related hospitalization in COPD

Background Hospital admissions are important contributors to the overall burden of chronic obstructive pulmonary disease (COPD). Understanding the patterns and causes of hospital admissions will help to identify targets for preventive interventions. This study aimed to determine the 5-year all-cause hospital admission trajectories of patients with COPD following their first ever exacerbation-related hospitalisation. Methods Patients with COPD were identified from the Danish national registries. Patients experiencing their first ever exacerbation-related hospitalisation, defined as the index event, between 2000 and 2014 were included. All-cause hospital admissions were examined during a subsequent 5-year follow-up period, and categorised using the International Classification of Diseases, 10th revision. Results In total, 82 964 patients with COPD were included. The mean±sd age was 72±10 years and 48% were male. Comorbidities were present in 58%, and 65% of the patients collected inhalation medication ≤6 months prior to the index event. In total, 337 066 all-cause hospital admissions were identified, resulting in a 5-year admission rate of 82%. Most admissions were due to nonrespiratory causes (59%), amongst which cardiac events were most common (19%). Conclusion Hospital admissions following a first exacerbation-related hospitalisation are common; nonrespiratory events constitute the majority of admissions. Besides the respiratory causes, treatment targeting the nonrespiratory causes of hospital admission should be considered to effectively decrease the burden of hospitalisation in COPD

Activity of the efflux pump inhibitor SILA 421 against drug-resistant tuberculosis

Organosilicon compounds are efflux pump inhibitors with potency as an antituberculosis drug. Of the organisilicon compounds tested, SILA 421 has been shown to have a highest potency as an antituberculosis drug (1). It shares the common pathways for antimycobacterial killing with other efflux pump inhibitors: it revealed direct in vitro activity against M. tuberculosis (1), it has been shown to modify resistance by inhibiting mdr-1 efflux pumps and has shown to enhance killing of M. tuberculosis by macrophages (1)

The effects of signal transducer and activator of transcription three mutations on human platelets

Involvement of signal transducer and activator of transcription 3 (STAT3) in inflammation is well known. Recently, a role for STAT3 in platelet activation and platelet production has been suggested. Platelets exhibit important immune functions and engagement of STAT3 in platelet physiology may link inflammation and hemostasis. This study investigated the effects of STAT3 loss-of-function mutations and single nucleotide polymorphisms (SNPs) in STAT3 on glycoprotein VI (GPVI)-mediated platelet activation and platelet numbers in humans. Two cohorts were studied. The first cohort concerned patients with STAT3 loss-of-function mutations. Platelet numbers were investigated in eight patients and GPVI-mediated platelet activation was functionally tested in four patients. Additional experiments were performed to investigate underlying mechanisms. The second cohort concerned 334 healthy volunteers and investigated the consequences of SNPs in STAT3 on GPVI-mediated platelet activation and platelet numbers. Platelet activation was lower in STAT3 loss-of-function patients at baseline and after stimulation of the GPVI receptor, reflected by decreased P-selectin expression. This was independent of gene transcription. Blockade of the adenosine di-phosphate (ADP) pathway resulted in a further decrease of P-selectin expression, particularly in STAT3 loss-of-function patients. In contrast, the SNPs in STAT3 did not influence GPVI-mediated platelet activation. Also, platelet numbers were not affected by STAT3 loss-of-function mutations, nor was there an association with the SNPs. In conclusion, STAT3 signaling does not seem to play a major role in thrombopoiesis. We confirm that STAT3 is involved in GPVI-mediated platelet activation in humans, independent of gene transcription. GPVI-mediated platelet activation is highly dependent on secondary ADP release. Our findings suggest that STAT3 modulation may affect inflammation, hemostasis, and their interaction.</p

Chronic obstructive pulmonary disease and atrial fibrillation:an interdisciplinary perspective

Chronic obstructive pulmonary disease (COPD) is highly prevalent among patients with atrial fibrillation (AF), shares common risk factors, and adds to the overall morbidity and mortality in this population. Additionally, it may promote AF and impair treatment efficacy. The prevalence of COPD in AF patients is high and is estimated to be ∼25%. Diagnosis and treatment of COPD in AF patients requires a close interdisciplinary collaboration between the electrophysiologist/cardiologist and pulmonologist. Differential diagnosis may be challenging, especially in elderly and smoking patients complaining of unspecific symptoms such as dyspnoea and fatigue. Routine evaluation of lung function and determination of natriuretic peptides and echocardiography may be reasonable to detect COPD and heart failure as contributing causes of dyspnoea. Acute exacerbation of COPD transiently increases AF risk due to hypoxia-mediated mechanisms, inflammation, increased use of beta-2 agonists, and autonomic changes. Observational data suggest that COPD promotes AF progression, increases AF recurrence after cardioversion, and reduces the efficacy of catheter-based antiarrhythmic therapy. However, it remains unclear whether treatment of COPD improves AF outcomes and which metric should be used to determine COPD severity and guide treatment in AF patients. Data from non-randomized studies suggest that COPD is associated with increased AF recurrence after electrical cardioversion and catheter ablation. Future prospective cohort studies in AF patients are needed to confirm the relationship between COPD and AF, the benefits of treatment of either COPD or AF in this population, and to clarify the need and cost-effectiveness of routine COPD screening

Twin GEM-TPC prototype (HGB4) beam test at GSI and Jyväskylä : a development for the Super-FRS at FAIR

The FAIR facility is an international accelerator centre for research with ion and antiproton beams. It is being built at Darmstadt, Germany as an extension to the current GSI research institute. One major part of the facility will be the Super-FRS[2] separator, which will be include in phase one of the project construction. The NUSTAR experiments will benefit from the Super-FRS, which will deliver an unprecedented range of radioactive ion beams (RIB). These experiments will use beams of different energies and characteristics in three different branches; the high-energy which utilizes the RIB at relativistic energies 300-1500 MeV/u as created in the production process, the low-energy branch aims to use beams in the range of 0-150 MeV/u whereas the ring branch will cool and store beams in the NESR ring. The main tasks for the Super-FRS beam diagnostics chambers will be for the set up and adjustment of the separator as well as to provide tracking and event-by-event particle identification. The Helsinki Institute of Physics, and the Detector Laboratory and Experimental Electronics at GSI are in a joint R&D of a GEM-TPC detector which could satisfy the requirements of such tracking detectors, in terms of tracking efficiency, space resolution, count rate capability and momenta resolution. The current prototype, which is the generation four of this type, is two GEM-TPCs in twin configuration inside the same vessel. This means that one of the GEM-TPC is flipped on the middle plane w.r.t. the other one. This chamber was tested at Jyväskylä accelerator with protons projectiles and at GSI with Uranium, fragments and Carbon beams during this year 2016.Peer reviewe

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362