Age-related variations in corneal biomechanical properties

Purpose To determine age-related changes in corneal viscoelastic properties in healthy individuals. Methods This observational cross-sectional study was performed at the Department of Ophthalmology, Imam Khomeini Hospital, Ahvaz, Iran and included 302 healthy individuals in 6 age decades (range: 10�69 years). After complete ocular examination, corneal viscoelastic properties were measured by ocular response analyzer and central corneal thickness (CCT) by an ultrasonic pachymeter. Our main outcome measures were corneal viscoelastic properties in different age groups. Results Corneal hysteresis (CH) and corneal resistance factor (CRF) showed a significant negative correlation with age (P < 0.001 for both, r = �0.353 and r = �0.246, respectively). Female gender had significantly higher CH (P = 0.017) and CRF (P = 0.019). CH and CRF were significantly correlated (P < 0.001, r = 0.821). CCT showed a biphasic pattern with significantly higher thicknesses before 20 and after 50 years of age. CH and CRF were significantly correlated with CCT (P < 0.001 for both, r = 0.21 and r = 0.26, respectively) and intraocular pressure (IOP) (P < 0.001 for both, r = �0.474 and r = 0.598, respectively). Corneal-compensated IOP (IOPcc) was significantly higher after age 40 compared to age group <20 (p < 0.045). Goldmann-correlated IOP (IOPg) was significantly correlated with CCT (P = 0.001, r = 0.193), while IOPcc showed no correlation with CCT (P = 0.265, r = 0.062). CH was significantly higher in hyperopic eyes compared to emmetropic eyes (P = 0.009) and myopic eye (P < 0.001). Conclusions In this study, there was a decrease in CH and CRF with an increase in age. Hyperopia and female gender are associated with higher CH and CRF. CCT is higher toward the extremes of life and is significantly correlated with CH and CRF. © 2016 Iranian Society of Ophthalmolog

Age-related variations in corneal biomechanical properties

Purpose To determine age-related changes in corneal viscoelastic properties in healthy individuals. Methods This observational cross-sectional study was performed at the Department of Ophthalmology, Imam Khomeini Hospital, Ahvaz, Iran and included 302 healthy individuals in 6 age decades (range: 10�69 years). After complete ocular examination, corneal viscoelastic properties were measured by ocular response analyzer and central corneal thickness (CCT) by an ultrasonic pachymeter. Our main outcome measures were corneal viscoelastic properties in different age groups. Results Corneal hysteresis (CH) and corneal resistance factor (CRF) showed a significant negative correlation with age (P < 0.001 for both, r = �0.353 and r = �0.246, respectively). Female gender had significantly higher CH (P = 0.017) and CRF (P = 0.019). CH and CRF were significantly correlated (P < 0.001, r = 0.821). CCT showed a biphasic pattern with significantly higher thicknesses before 20 and after 50 years of age. CH and CRF were significantly correlated with CCT (P < 0.001 for both, r = 0.21 and r = 0.26, respectively) and intraocular pressure (IOP) (P < 0.001 for both, r = �0.474 and r = 0.598, respectively). Corneal-compensated IOP (IOPcc) was significantly higher after age 40 compared to age group <20 (p < 0.045). Goldmann-correlated IOP (IOPg) was significantly correlated with CCT (P = 0.001, r = 0.193), while IOPcc showed no correlation with CCT (P = 0.265, r = 0.062). CH was significantly higher in hyperopic eyes compared to emmetropic eyes (P = 0.009) and myopic eye (P < 0.001). Conclusions In this study, there was a decrease in CH and CRF with an increase in age. Hyperopia and female gender are associated with higher CH and CRF. CCT is higher toward the extremes of life and is significantly correlated with CH and CRF. © 2016 Iranian Society of Ophthalmolog

Customized clinical practice guidelines for management of adult cataract in Iran

Purpose: To customize clinical practice guidelines (CPGs) for cataract management in the Iranian population. Methods: First, four CPGs (American Academy of Ophthalmology 2006 and 2011, Royal College of Ophthalmologists 2010, and Canadian Ophthalmological Society 2008) were selected from a number of available CPGs in the literature for cataract management. All recommendations of these guidelines, together with their references, were studied. Each recommendation was summarized in 4 tables. The first table showed the recommendation itself in clinical question components format along with its level of evidence. The second table contained structured abstracts of supporting articles related to the clinical question with their levels of evidence. The third table included the customized recommendation of the internal group respecting its clinical advantage, cost, and complications. In the fourth table, the internal group their recommendations from 1 to 9 based on the customizing capability of the recommendation (applicability, acceptability, external validity). Finally, customized recommendations were sent one month prior to a consensus session to faculty members of all universities across the country asking for their comments on recommendations. Results: The agreed recommendations were accepted as conclusive while those with no agreement were discussed at the consensus session. Finally, all customized recommendations were codified as 80 recommendations along with their sources and levels of evidence for the Iranian population. Conclusion: Customization of CPGs for management of adult cataract for the Iranian population seems to be useful for standardization of referral, diagnosis and treatment of patients. © 2015 Journal of Ophthalmic and Vision Research | Published by Wolters Kluwer - Medknow

Microstructure, texture and tensile properties of ultrafine/nano grained magnesium alloy processed by accumulative back extrusion

An AZ31 wrought magnesium alloy was processed by employing multipass accumulative back extrusion process. The obtained microstructure, texture and room temperature tensile properties were characterized and discussed. Ultrafine grained microstructure including nano grains were developed, where the obtained mean grain size was decreased from 8 to 0.5 µm by applying consecutive passes. The frequency of both low angle and high angle boundaries increased after processing. Strength of the experimental alloy was decreased after processing, which was attributed to the obtained texture involving the major component lying inclined to the deformation axis. Both the uniform and post uniform elongations of the processed materials were increased after processing, where a total elongation of 68 pct was obtained after six-pass deformation. The contribution of different twinning and slip mechanism was described by calculating corresponding Schmid factors. The operation of prismatic slip was considered as the major deformation contributor. The significant increase in post uniform deformation of the processed material was discussed relying on the occurrence of grain boundary sliding associated with the operation of prismatic slip.Postprint (author's final draft

Microfluidic analysis techniques for safety assessment of pharmaceutical nano- and microsystems

This chapter reviews the evolution of microfabrication methods and materials, applicable to manufacturing of micro total analysis systems (or lab‐on‐a‐chip), from a general perspective. It discusses the possibilities and limitations associated with microfluidic cell culturing, or so called organ‐on‐a‐chip technology, together with selected examples of their exploitation to characterization of pharmaceutical nano‐ and microsystems. Materials selection plays a pivotal role in terms of ensuring the cell adhesion and viability as well as defining the prevailing culture conditions inside the microfluidic channels. The chapter focuses on the hepatic safety assessment of nanoparticles and gives an overview of the development of microfluidic immobilized enzyme reactors that could facilitate examination of the hepatic effects of nanomedicines under physiologically relevant conditions. It also provides an overview of the future prospects regarding system‐level integration possibilities facilitated by microfabrication of miniaturized separation and sample preparation systems as integral parts of microfluidic in vitro models.Non peer reviewe

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation &lt;92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p&lt;0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p&lt;0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome