Whole-genome characterization of a Shewanella algae strain coharboring blaCTX-M-15 and armA genes on a novel IncC plasmid

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Health status in COPD cannot be measured by the St George's Respiratory Questionnaire alone: an evaluation of the underlying concepts of this questionnaire

Contains fulltext : 88421.pdf (publisher's version ) (Open Access)BACKGROUND: Improving patients' health status is one of the major goals in COPD treatment. Questionnaires could facilitate the guidance of patient-tailored disease management by exploring which aspects of health status are problematic, and which aspects are not. Health status consists of four main domains (physiological functioning, symptoms, functional impairment, and quality of life), and at least sixteen sub-domains. A prerequisite for patient-tailored treatment is a detailed assessment of all these sub-domains. Most questionnaires developed to measure health status consist of one or a few subscales and measure merely some aspects of health status. The question then rises which aspects of health status are measured by these instruments, and which aspects are not covered. As it is one of the most frequently used questionnaires in COPD, we evaluated which aspects of health status are measured and which aspects are not measured by the St George's Respiratory Questionnaire (SGRQ). METHODS: One hundred and forty-six outpatients with COPD participated. Correlations were calculated between the three sections of the SGRQ and ten sub-domains of the Nijmegen Integral Assessment Framework, covering Symptoms, Functional Impairment, and Quality of Life. As the SGRQ was not expected to measure physiological functioning, we did not include this main domain in the statistical analyses. Pearson's r > or = 0.70 was used as criterion for conceptual similarity. RESULTS: The SGRQ sections Symptoms and Total showed conceptual similarity with the sub-domain Subjective Symptoms (main domain Symptoms). The sections Activity, Impacts and Total were conceptual similar to Subjective Impairment (main domain Functional Impairment). The SGRQ sections were not conceptual similar to other sub-domains of Symptoms, Functional Impairment, nor to any sub-domain of Quality of Life. CONCLUSIONS: The SGRQ could facilitate the guidance of disease management in COPD only partially. The SGRQ is appropriately only for measuring problems in the sub-domains Subjective Symptoms and Subjective Impairment, and not for measuring problems in other sub-domains of health status, such as Quality of Life

Municipal mortality due to thyroid cancer in Spain

BACKGROUND: Thyroid cancer is a tumor with a low but growing incidence in Spain. This study sought to depict its spatial municipal mortality pattern, using the classic model proposed by Besag, York and Mollié. METHODS: It was possible to compile and ascertain the posterior distribution of relative risk on the basis of a single Bayesian spatial model covering all of Spain's 8077 municipal areas. Maps were plotted depicting standardized mortality ratios, smoothed relative risk (RR) estimates, and the posterior probability that RR > 1. RESULTS: From 1989 to 1998 a total of 2,538 thyroid cancer deaths were registered in 1,041 municipalities. The highest relative risks were mostly situated in the Canary Islands, the province of Lugo, the east of La Coruña (Corunna) and western areas of Asturias and Orense. CONCLUSION: The observed mortality pattern coincides with areas in Spain where goiter has been declared endemic. The higher frequency in these same areas of undifferentiated, more aggressive carcinomas could be reflected in the mortality figures. Other unknown genetic or environmental factors could also play a role in the etiology of this tumor

Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Measuring decrement in change-of-direction speed across repeated sprints in basketball: Novel vs. traditional approaches

Dalbo, VJ ORCiD: 0000-0002-5944-7558; Guy, JH ORCiD: 0000-0003-3000-2747; Madueno, MC ORCiD: 0000-0002-1726-0680; Scanlan, AT ORCiD: 0000-0002-0750-8697Approaches to quantify decrement in change-of-direction speed during repeated sprints in basketball players have traditionally used total performance time, which is strongly influenced by linear speed. The purpose of this study was to compare performance decrement across change-of-direction sprints using total performance time and a novel approach that better isolates change-of-direction speed, termed change-of-direction deficit (CODD). Semiprofessional basketball players (N = 8; 19.9 ± 1.5 years; 183.0 ± 9.6 cm; 77.7 ± 16.9 kg) completed 12 × 20-m change-of-direction sprints (Agility 5-0-5 trials) with 20-second recoveries between each sprint. Agility 5-0-5 performance time was taken as the duration to cover 5 m immediately before and after (10 m in total) a 180° directional change. Change-of-direction deficit was calculated as the difference between mean 10- and 20-m split time determined during reference 20-m linear sprints in a separate session and Agility 5-0-5 time in each sprint. Performance decrement was calculated for each approach as: ([total time/ideal time] × 100) - 100. Comparisons between approaches were made using a paired-sample t-test, effect size analyses, and magnitude-based inferences. A significantly greater (P < 0.001; effect size = 2.16, very large; almost certainly higher) performance decrement was apparent using CODD (5.99 ± 1.88%) than Agility 5-0-5 performance time (2.84 ± 0.84%). The present findings indicate that change-of-direction speed measured with CODD shows promise in providing different insight and deteriorates more than total performance time during repeated sprints in basketball players. Change-of-direction deficit has potential to better isolate decrements in change-of-direction speed across repeated sprints compared with total performance time. Scanlan, AT, Madueno, MC, Guy, JH, Giamarelos, K, Spiteri, T, and Dalbo, VJ. Measuring decrement in change-of-direction speed across repeated sprints in basketball: Novel vs. traditional approaches. J Strength Cond Res XX(X): 000-000, 2018