In this issue of Proietti

In this Dihydromyricetin manufacturer issue of , Proietti and colleagues () analyzed pooled datasets (n=3646) from SPORTIF III and V trials of warfarin-treated patients dependent on renal function. Diminished creatinine clearance (<60ml/min) was reported in 952 (26%) patients. Overall, the time in therapeutic range (TTR) was higher in patients with normal renal function compared to those with RI (p<0.001). By logistic regression, chronic atrial fibrillation and male gender were associated with TTR>70%, whilst diabetes mellitus, aspirin use and RI were inversely associated with TTR>70%. On Cox analysis, RI was an independent predictor for stroke (p=0.006) and death (p<0.001); while TTR>70% was independently associated with a lower risk of stroke (p=0.024), death (p=0.001) and major bleeding (p=0.001). The combined SPORTIF warfarin data suggest that RI is highly prevalent among patients with atrial fibrillation, being a risk factor for stroke and death. Adjusting for RI, good quality anticoagulation control (TTR>70%) was an independent predictor for lower risks of stroke, death and major bleeding.
There are few important considerations yielded from these latest elegant data. Importantly, patients with even mild RI experience much more frequent vascular thrombotic events than patients with normal kidney function. The index data are in full agreement that despite huge differences among the trials with regard to exclusions, baseline characteristics, randomization or enrollment patterns, and length of follow up, RI patients have consistently higher risks to experience primary vascular endpoint event despite even a very liberal eGRF or creatinine clearance of <60ml/min cut-off to triage RI cohorts. Also, the RI patients experience much more frequent bleeding events, especially those with non-adjusted TTR. These two disturbing findings raise obvious concerns that we may consider OAC dose/regimen downgrades in such patients, the strategy which is currently not recommended by the regulatory agencies. The problem is that RI patients constitute no >10–15% of the entire trial pool generating woefully small dataset(s) for each particular OAC. Dichotomizing patients further into severe, mild, or moderate RI, make such groups very small, usually in double-digit numbers hence preventing quality analyses. These circumstances allow the regulatory authorities to ignore such obvious shortcomings, or/and demand unbiased risk assessment in RI patients receiving OAC. Indeed, the fact that patients exhibited such poor outcomes in RI, () we should consider the advantage of non-Vitamin K antagonist oral anticoagulants (NOACs) over warfarin. Indeed, there is some evidence () that NOACs may be superior to warfarin causing less bleeding complications. However, all OAC mega trials suffer from massive double-digit incomplete follow-up rates, challenging the quality of the analyzed datasets (). Overall, the current knowledge suggests no single superior OAC choice with regard to their safety and efficacy in patients with RI (). Further comparative randomized studies of different OACs in patients with moderate and severe RI are urgently needed.
Disclosure

Background
In this issue of EBioMedicine, Roerecke and Colleagues report that, in Japan, alcohol consumption as low as <20g daily was associated with significant protection from incident and prevalent fatty liver; however, no such association was found in countries other than Japan (Roerecke et al., 2016). This systematic review is based on the analysis of 18 articles (11 of which are from Japan) which recruited, overall, 99,370 participants, 25,662 of whom had steatosis.
Steatosis
Steatosis defines fatty changes either in >5% of hepatocytes based on histological analysis or >5.6% based on findings from proton magnetic resonance spectroscopy (EASL-EAS-EASO, 2016). Often, steatosis is diagnosed with ultrasonography both in clinical practice and in the research arena (Ballestri et al., 2015, 2016a).
A large variety of causes, notably including alcohol consumption, may eventually be conducive to accumulation of intrahepatic fat (EASL-EAS-EASO, 2016). In recent years nonalcoholic fatty liver disease (NAFLD) has reached massive proportions worldwide and has an epidemic diffusion in certain high-risk groups. However, the rationale for distinguishing alcoholic from nonalcoholic fatty liver disease has been questioned based on shared clinico-pathological commonalities (Völzke, 2012).

Introduction Worldwide Glaucoma is the second most common cause

Introduction
Worldwide, Glaucoma is the second most common cause of irreversible visual loss, with its prevalence in South India varying between 1.62% and 2.6%.
A chronic optic neuropathy with characteristic structural and functional changes in the optic nerve head, an important risk factor for glaucoma is increased Intraocular pressure (IOP). A normal Dihydromyricetin manufacturer intraocular pressure is essential to maintain the shape of the eye and visual function with prolonged elevation in IOP resulting in irreversible damage to the retinal ganglion Dihydromyricetin manufacturer and postganglionic nerve fibres. Detecting the IOP is essential in not only initiating treatment, but also in monitoring the response to treatment. The past few decades have seen a rapid evolution of tonometry instrumentation to ensure more accurate measurement of IOP. However, both ocular and nonocular factors often exert confounding influences in the accurate measurement of the IOP and complicate the treatment.

Materials and method
This study was approved by the Institute Research Board and Ethical Committee. Over a 4month period (January–April 2013), patients of both sexes between the ages of 20–80years attending the outpatient services were randomly screened and included in this study. Patients with pre-existing corneal pathologies and nystagmus were excluded from the study. The IOP was measured by a single investigator using the Noncontact Tonometer, Perkin’s applanation tonometer and Schiotz indentation tonometer in that order to prevent lowering of IOP induced by contact. In all cases, a 5min interval was ensured between any two methods of IOP measurement and an average of three measurements was taken as the final IOP obtained by that method. CCT was measured with the Altair Ultrasonic pachymeter after tonometric measurements had been completed.
Finally, the patient was placed in a supine position and asked to fix at a target. Zero error of Schiotz indentation tonometer (Medetz Surgical, USA) was taken by placing the footplate on the test block provided. The eyelids were separated by hand without exerting pressure on the globe, and the tonometer foot plate was placed on the anaesthetized cornea so that the plunger moved freely vertically. The scale reading was noted. The 5.5gram weight was initially used, but if scale reading was four or less additional weights were added to the plunger. The subsequent readings were taken with additional weights to overcome the influence of sclera rigidity. These readings were converted to IOP measurement in mm of Hg by using Friedenwald’s table.
Following the completion of IOP measurements, the ultrasonic pachymetry probe (Optikon 2000 S.p.A, Altair, Rome, Italy) was placed on the centre of the anaesthetized cornea. Three consecutive readings were taken and averaged to get the central corneal thickness. CCT values were categorized as per the findings of the Los Angeles Latino Eye Study Group.
Statistical analyses were performed using MedCalc for Windows, version 13.3.1 (MedCalc Software, Ostend, Belgium). IOP measurements were compared to those obtained by the Perkin’s handheld applanation tonometer which was assumed to be the gold standard (Sensitivity, specificity, positive and negative predictive values). Regression Analysis was also performed to determine any causal relationship (Dependant variable -Perkin’s Tonometer IOP; Independent variables- Noncontact tonometer IOP, Schiotz tonometer IOP, age, gender and CCT). A Bland–Altman plot was constructed to investigate the existence of any systematic difference between the different tonometry methods.

Discussion
Population screening for glaucoma based solely on IOP may not be necessarily identifying all patients due to variable response of the human eye to the changing IOP. Although multiple risk factors can account for the susceptibility to glaucomatous damage, the IOP is the only risk factor mutation rate is amenable to treatment by pharmacological and surgical measures. Baseline values of the IOP will help the clinician in monitoring progress of the disease and response to treatment. While a number of tonometers are available for measuring the IOP, each has its own advantages and disadvantages. The increased costs and the need for specialized training for optimal utilization of modern tonometers preclude the use of such tonometers in the rural camp setting and outreach mass screening programmes.