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Concept: Trigraph


BACKGROUND:Case reports indicate that the use of fluoroquinolones may lead to acute kidney injury. We studied the association between the use of oral fluoroquinolones and acute kidney injury, and we examined interaction with renin-angiotensin-system blockers. METHODS:We formed a nested cohort of men aged 40-85 enrolled in the United States IMS LifeLink Health Plan Claims Database between 2001 and 2011. We defined cases as men admitted to hospital for acute kidney injury, and controls were admitted to hospital with a different presenting diagnosis. Using risk-set sampling, we matched 10 controls to each case based on hospital admission, calendar time (within 6 wk), cohort entrance (within 6 wk) and age (within 5 yr). We used conditional logistic regression to assess the rate ratio (RR) for acute kidney injury with current, recent and past use of fluoroquinolones, adjusted by potential confounding variables. We repeated this analysis with amoxicillin and azithromycin as controls. We used a case-time-control design for our secondary analysis. RESULTS:We identified 1292 cases and 12 651 matched controls. Current fluoroquinolone use had a 2.18-fold (95% confidence interval [CI] 1.74-2.73) higher adjusted RR of acute kidney injury compared with no use. There was no association between acute kidney injury and recent (adjusted RR 0.87, 95% CI 0.66-1.16) or past (RR 0.86, 95% CI 0.66-1.12) use. The absolute in crease in acute kidney injury was 6.5 events per 10 000 person-years. We observed 1 additional case per 1529 patients given fluoroquinolones or per 3287 prescriptions dispensed. The dual use of fluoroquinolones and renin- angiotensin-system blockers had an RR of 4.46 (95% CI 2.84-6.99) for acute kidney injury. Our case-time-control analysis confirmed an increased risk of acute kidney injury with fluoroquinolone use (RR 2.16, 95% CI 1.52-3.18). The use of amoxicillin or azithro mycin was not associated with acute kidney injury. INTERPRETATION:We found a small, but significant, increased risk of acute kidney injury among men with the use of oral fluoroquinolones, as well as a significant interaction between the concomitant use of fluoroquinolones and renin- angiotensin-system blockers.

Concepts: Logistic regression, Acute kidney injury, Confounding, Trigraph, Gh, Case, Statistical terminology, Quinolone


BACKGROUND: The benefits of exercise are well established but one major barrier for many is time. It has been proposed that short period resistance training (RT) could play a role in weight control by increasing resting energy expenditure (REE) but the effects of different kinds of RT has not been widely reported. METHODS: We tested the acute effects of high-intensity interval resistance training (HIRT) vs. traditional resistance training (TT) on REE and respiratory ratio (RR) at 22 hours post-exercise. In two separate sessions, seventeen trained males carried out HIRT and TT protocols. The HIRT technique consists of: 6 repetitions, 20 seconds rest, 2/3 repetitions, 20 secs rest, 2/3 repetitions with 2[prime]30[prime][prime] rest between sets, three exercises for a total of 7 sets. TT consisted of eight exercises of 4 sets of 8–12 repetitions with one/two minutes rest with a total amount of 32 sets. We measured basal REE and RR (TT0 and HIRT0) and 22 hours after the training session (TT22 and HIRT22). RESULTS: HIRT showed a greater significant increase (p < 0.001) in REE at 22 hours compared to TT (HIRT22 2362 +/- 118 Kcal/d vs TT22 1999 +/- 88 Kcal/d). RR at HIRT22 was significantly lower (0.798 +/- 0.010) compared to both HIRT0 (0.827 +/- 0.006) and TT22 (0.822 +/- 0.008). CONCLUSIONS: Our data suggest that shorter HIRT sessions may increase REE after exercise to a greater extent than TT and may reduce RR hence improving fat oxidation. The shorter exercise time commitment may help to reduce one major barrier to exercise.

Concepts: Physical exercise, Exercise, Training, Strength training, Weight training, Trigraph, Gh, Order theory


ProCESS Investigators, Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, Terndrup T, Wang HE, Hou PC, LoVecchio F, Filbin MR, Shapiro NI, Angus DC. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014; 370:1683-93.

Concepts: Randomized controlled trial, Shock, Trigraph, Gh, Septic shock, Sepsis, Chinese-language surnames


Background Andexanet alfa (andexanet) is a recombinant modified human factor Xa decoy protein that has been shown to reverse the inhibition of factor Xa in healthy volunteers. Methods In this multicenter, prospective, open-label, single-group study, we evaluated 67 patients who had acute major bleeding within 18 hours after the administration of a factor Xa inhibitor. The patients all received a bolus of andexanet followed by a 2-hour infusion of the drug. Patients were evaluated for changes in measures of anti-factor Xa activity and were assessed for clinical hemostatic efficacy during a 12-hour period. All the patients were subsequently followed for 30 days. The efficacy population of 47 patients had a baseline value for anti-factor Xa activity of at least 75 ng per milliliter (or ≥0.5 IU per milliliter for those receiving enoxaparin) and had confirmed bleeding severity at adjudication. Results The mean age of the patients was 77 years; most of the patients had substantial cardiovascular disease. Bleeding was predominantly gastrointestinal or intracranial. The mean (±SD) time from emergency department presentation to the administration of the andexanet bolus was 4.8±1.8 hours. After the bolus administration, the median anti-factor Xa activity decreased by 89% (95% confidence interval [CI], 58 to 94) from baseline among patients receiving rivaroxaban and by 93% (95% CI, 87 to 94) among patients receiving apixaban. These levels remained similar during the 2-hour infusion. Four hours after the end of the infusion, there was a relative decrease from baseline of 39% in the measure of anti-factor Xa activity among patients receiving rivaroxaban and of 30% among those receiving apixaban. Twelve hours after the andexanet infusion, clinical hemostasis was adjudicated as excellent or good in 37 of 47 patients in the efficacy analysis (79%; 95% CI, 64 to 89). Thrombotic events occurred in 12 of 67 patients (18%) during the 30-day follow-up. Conclusions On the basis of a descriptive preliminary analysis, an initial bolus and subsequent 2-hour infusion of andexanet substantially reduced anti-factor Xa activity in patients with acute major bleeding associated with factor Xa inhibitors, with effective hemostasis occurring in 79%. (Funded by Portola Pharmaceuticals; ANNEXA-4 number, NCT02329327 .).

Concepts: Coagulation, Hemostasis, Bleeding, Enzyme inhibitor, Arithmetic mean, Inhibitor, Trigraph, Prime number


U.S. sewage sludges were analyzed for 58 regulated and non-regulated elements by ICP-MS and electron microscopy to explore opportunities for removal and recovery. Sludge/water distribution coefficients (KD, L/kg dry weight) spanned five orders of magnitude, indicating significant metal accumulation in biosolids. Rare-earth elements and minor metals (Y, La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu) detected in sludges showed enrichment factors (EFs) near unity, suggesting dust or soils as likely dominant sources. In contrast, most platinum group elements (i.e., Ru, Rh, Pd, Pt) showed high EF and KD values, indicating anthropogenic sources. Numerous metallic and metal oxide colloids (<100-500 nm diameter) were detected; the morphology of abundant aggregates of primary particles measuring <100 nm provided clues to their origin. For a community of 1 million people, metals in biosolids were valued at up to US$13 million annually. A model incorporating a parameter (KD x EF x $Value) to capture the relative potential for economic value from biosolids revealed the identity of the 13 most lucrative elements (Ag, Cu, Au, P, Fe, Pd, Mn, Zn, Ir, Al, Cd, Ti, Ga and Cr) with a combined value of US $280/ton of sludge.

Concepts: Metal, Sewage treatment, Trigraph, Value, Gh, Terbium, Platinum group, Ytterbium


BACKGROUND: The scope of prehospital (PH) interventions has expanded recently-not always with clear benefit. PH crystalloid resuscitation has been challenged, particularly in penetrating trauma. Optimal PH crystalloid resuscitation strategies remain unclear in blunt trauma as does the influence of PH hypotension. The objective was to characterize outcomes for PH crystalloid volume in patients with and without PH hypotension. METHODS: Data were obtained from a multicenter prospective study of blunt injured adults transported from the scene with ISS > 15. Subjects were divided into HIGH (>500 mL) and LOW (≤500 mL) PH crystalloid groups. Propensity-adjusted regression determined the association of PH crystalloid group with mortality and acute coagulopathy (admission International Normalized Ratio, >1.5) in subjects with and without PH hypotension (systolic blood pressure [SBP], <90 mm Hg) after controlling for confounders. RESULTS: Of 1,216 subjects, 822 (68%) received HIGH PH crystalloid and 616 (51%) had PH hypotension. Initial base deficit and ISS were similar between HIGH and LOW crystalloid groups in subjects with and without PH hypotension. In subjects without PH hypotension, HIGH crystalloid was associated with an increase in the risk of mortality (hazard ratio, 2.5; 95% confidence interval [95% CI], 1.3-4.9; p < 0.01) and acute coagulopathy (odds ratio [OR], 2.2; 95% CI, 1.01-4.9; p = 0.04) but not in subjects with PH hypotension. HIGH crystalloid was associated with correction of PH hypotension on emergency department (ED) arrival (OR, 2.02; 95% CI, 1.06-3.88; p = 0.03). The mean corrected SBP in the ED was 104 mm Hg. Each 1 mm Hg increase in ED SBP was associated with a 2% increase in survival in subjects with PH hypotension (OR, 1.02; 95% CI, 1.01-1.03; p < 0.01). CONCLUSION: In severely injured blunt trauma patients, PH crystalloid more than 500 mL was associated with worse outcome in patients without PH hypotension but not with PH hypotension. HIGH crystalloid was associated with corrected PH hypotension. This suggests that PH resuscitation should be goal directed based on the presence or absence of PH hypotension. LEVEL OF EVIDENCE: Therapeutic study, level III.

Concepts: Blood, Hypertension, Blood pressure, PH, Trigraph, Hypotension, Penetrating trauma, Blunt trauma


PURPOSE Anaplastic oligodendrogliomas, pure (AO) and mixed (anaplastic oligoastrocytoma [AOA]), are chemosensitive, especially if codeleted for 1p/19q, but whether patients live longer after chemoradiotherapy is unknown. PATIENTS AND METHODS Eligible patients with AO/AOA were randomly assigned to procarbazine, lomustine, and vincristine (PCV) plus radiotherapy (RT) versus RT alone. The primary end point was overall survival (OS). Results Two hundred ninety-one eligible patients were randomly assigned: 148 to PCV plus RT and 143 to RT. For the entire cohort, there was no difference in median survival by treatment (4.6 years for PCV plus RT v 4.7 years for RT; hazard ratio [HR] = 0.79; 95% CI, 0.60 to 1.04; P = .1). Patients with codeleted tumors lived longer than those with noncodeleted tumors (PCV plus RT: 14.7 v 2.6 years, HR = 0.36, 95% CI, 0.23 to 0.57, P < .001; RT: 7.3 v 2.7 years, HR = 0.40, 95% CI, 0.27 to 0.60, P < .001), and the median survival of those with codeleted tumors treated with PCV plus RT was twice that of patients receiving RT (14.7 v 7.3 years; HR = 0.59; 95% CI, 0.37 to 0.95; P = .03). For those with noncodeleted tumors, there was no difference in median survival by treatment arm (2.6 v 2.7 years; HR = 0.85; 95% CI, 0.58 to 1.23; P = .39). In Cox models that included codeletion status, the adjusted OS for all patients was prolonged by PCV plus RT (HR = 0.67; 95% CI, 0.50 to 0.91; P = .01). CONCLUSION For the subset of patients with 1p/19q codeleted AO/AOA, PCV plus RT may be an especially effective treatment, although this observation was derived from an unplanned analysis.

Concepts: Clinical trial, Oncology, Trigraph, Cox Models, Oligodendroglioma


This work established background concentrations for the pseudo total (HNO(3) + H(2)O(2)-soluble), mobilisable (NH(4)-acetate + EDTA-soluble) and mobile (1 M NH(4)NO(3)-soluble) element fractions of Hungarian surface soils that can be used as reference values for the soil quality standards. The 193 soils investigated were taken from the Hungarian Soil Information and Monitoring System. The background values for Al, As, B, Cd, Co, Cr, Cu, Mn, Ni, Pb, Sr and Zn were given as a range covering 95% of the variance of the representative samples. The differences between observed element concentrations and the calculated background values indicated anthropogenic or pedogenic impact in each fraction. The comparison of the calculated background values with the Hungarian quality standards and the contamination limit values of other countries showed that the limit values of a certain region or country are not suitable for other areas. Generally, Mn and Al had the highest, while Cd had the lowest concentration in each fraction. Cr and Al were the least and Sr was the most mobile element. The principal component analysis indicated different geochemical and physico-chemical behaviour of the elements in the fractions; the pseudo total fraction was influenced more by the geological behaviour, while mobilisable and mobile fraction explained a much higher proportion of the total variance of soil physico-chemical properties than soil geochemical properties. The Cd-Ni and Co-Mn element pairs were always in the same principal component in each fractions indicating similar geogenic origin and showing that their solubility changes are similar in function of soil properties.

Concepts: Chemistry, Soil, Chemical element, Zinc, Copper, Principal component analysis, Trigraph, Law of total variance


OBJECTIVE: Early hematoma expansion is a known cause of morbidity and mortality in patients with intracerebral hemorrhage (ICH). The goal of this study was to identify clinical predictors of ICH growth in the acute stage. MATERIALS AND METHODS: We studied 201 patients with acute (<6h) deep ganglionic ICH. Patients underwent CT scan at baseline and hematoma expansion (>33% or >12.5ml increase) was determined on the second scan performed within 24h. Fourteen clinical and neuroimaging variables (age, gender, GCS at admission, hypertension, diabetes mellitus, kidney disease, stroke, hemorrhagic, antiplatelet use, anticoagulant use, hematoma density heterogeneity, hematoma shape irregularity, hematoma volume and presence of IVH) were registered. Additionally, blood pressure was registered at initial systolic BP (i-SBP) and systolic BP 1.5h after admission (1.5h-SBP). The discriminant value of the hematoma volume and 1.5h-SBP for hematoma expansion were determined by the receiver operating characteristic (ROC) curves. Factors associated with hematoma expansion were analyzed with multiple logistic regression. RESULTS: Early hematoma expansion occurred in 15 patients (7.0%). The cut-off value of hematoma volume and 1.5h-SBP were determined to be 16ml and 160mmHg, respectively. Hematoma volume above 16ml (HV>16) ([OR]=5.05, 95% CI 1.32-21.36, p=0.018), hematoma heterogeneity (HH) ([OR]=7.81, 95% CI 1.91-40.23, p=0.004) and 1.5h-SBP above 160mmHg (1.5h-SBP>160) ([OR]=8.77, 95% CI 2.33-44.56, p=0.001) independently predicted ICH expansion. If those three factors were present, the probability was estimated to be 59%. CONCLUSIONS: The presented model (HV>16, HH, 1.5h-SBP>160) can be a practical tool for prediction of ICH growth in the acute stage. Further prospective studies are warranted to validate the ability of this model to predict clinical outcome.

Concepts: Regression analysis, Hypertension, Diabetes mellitus, Stroke, Blood pressure, Prediction, Trigraph, Cerebral hemorrhage


The aim of this paper was to determine the content of minor and major elements in apples by inductively coupled plasma atomic emission spectrometry (ICP-AES). Prior to ICP-AES measurement, dried apples were digested in a microwave assisted digestion system. The differences in the measured element concentrations after application of open and closed microwave system as sample preparation procedures are discussed. In whole apples, flesh and peel Ag, Al, Ba, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, Pb, Sr and Zn were analysed after optimisation and validating the analytical method using ICP-AES. The accuracy of the method determined by spiking experiments was very good (recoveries 88-115%) and the limits of detection of elements of interest were from 0.01 up to 14.7 μg g(-1). The reference ranges determined in all apple samples are 39-47 mg g(-1) for K, 9-14 mg g(-1) for Na, 3-7 mg g(-1) for Mg, 3-7 μg g(-1) for Zn, 0.7-2.8 μg g(-1) for Sr. The range of Mn in peel 4-6 μg g(-1) is higher compared to whole apple from 0.7 to 1.7 μg g(-1). Cd is found only in peel, in the concentration range of 0.4-1.1 μg g(-1).

Concepts: Electromagnetic radiation, Chemistry, Chemical element, Trigraph, Gh, Digestion, Atomic emission spectroscopy, Emission spectroscopy