Testing rimegepant for migraine—time to revise the trial design?

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Wearable Sensor for Real-time Monitoring of Hydrogen Peroxide in Simulated Exhaled Air

In this work, an innovative and cheap electrochemical sensor for hydrogen peroxide quantification in exhaled breath was developed. H2O2 is the most used biomarker among the Reactive Oxygen Species (ROS) for monitoring the level of oxidative stress in the respiratory system. This is due to its stability and ability to cross biological membranes and also because it is detectable in extracellular space. The electrochemical sensor was obtained using the silver layer of wasted compact discs (CDs). All three electrodes, working (WE), counter (CE), and pseudo-reference electrode (RE), were fabricated using a laser cutter. The working electrode was used directly, while an Ag/AgCl paste and a graphite paste were applied respectively on the RE and the CE. In addition, a chitosan layer was deposited by Electro-Phoretic Deposition (EPD) on the surface of the sensor. This biopolymer improves the wettability of the sensor in presence of a humid atmosphere such as that given by exhaled air. The sensor was tested in both liquid and nebulized solutions containing different concentrations of hydrogen peroxide. The detection of H2O2 was evaluated using Linear Sweep Voltammetry (LSV) as electrochemical technique. The results show that the peak current increases linearly with hydrogen peroxide concentration from 100 to 500 μM with a sensitivity of 0.068 µA µM−1 cm−2 and 0.108 µA µM−1 cm−2, a Limit Of Detection (LOD) of 60 μM and 30 μM respectively for liquid and nebulized solutions. Therefore, the use of the electrochemical sensor can allow the monitoring of hydrogen peroxide in real time with good results

Renal function decline in older men and women with advanced CKD:Results from the EQUAL study

INTRODUCTION: Understanding the mechanisms underlying the differences in renal decline between men and women may improve sex-specific clinical monitoring and management. To this end, we aimed to compare the slope of renal function decline in older men and women in chronic kidney disease (CKD) Stages 4 and 5, taking into account informative censoring related to the sex-specific risks of mortality and dialysis initiation. METHODS: The European QUALity Study on treatment in advanced CKD (EQUAL) study is an observational prospective cohort study in Stages 4 and 5 CKD patients ≥65 years not on dialysis. Data on clinical and demographic patient characteristics were collected between April 2012 and December 2018. Estimated glomerular filtration rate (eGFR) was calculated using the CKD Epidemiology Collaboration equation. eGFR trajectory by sex was modelled using linear mixed models, and joint models were applied to deal with informative censoring. RESULTS: We included 7801 eGFR measurements in 1682 patients over a total of 2911 years of follow-up. Renal function declined by 14.0% [95% confidence interval (CI) 12.9–15.1%] on average each year. Renal function declined faster in men (16.2%/year, 95% CI 15.9–17.1%) compared with women (9.6%/year, 95% CI 6.3–12.1%), which remained largely unchanged after accounting for various mediators and for informative censoring due to mortality and dialysis initiation. Diabetes was identified as an important determinant of renal decline specifically in women. CONCLUSION: In conclusion, renal function declines faster in men compared with women, which remained similar after adjustment for mediators and despite a higher risk of informative censoring in men. We demonstrate a disproportional negative impact of diabetes specifically in women

Effect of Vitamin D Receptor Activation on the AGE/RAGE System and Myeloperoxidase in Chronic Kidney Disease Patients

Vitamin D receptor (VDR) activation has been reported to increase circulating levels of the advanced glycation end products (AGE) and their decoy receptor (RAGE). However, until now, the effect of VDR activation on AGE and RAGE has not been tested in the setting of a randomized, double-blind clinical trial. We have therefore analyzed the effect of VDR activation by paricalcitol on pentosidine, S100A12/ENRAGE, and RAGE and on established biomarkers of oxidative stress like myeloperoxidase in CKD patients in the PENNY trial. At baseline, human S100A12/ENRAGE, RAGE, and myeloperoxidase, but not pentosidine, were intercorrelated, and the association between S100A12/ENRAGE and myeloperoxidase (r=0.71, P<0.001) was the strongest among these correlations. Paricalcitol failed to modify biomarkers of the AGE/RAGE system and myeloperoxidase in unadjusted and adjusted analyses by the generalized linear model (GLM). No effect modification by other risk factors was registered. Paricalcitol does not modify biomarkers of the AGE/RAGE system and myeloperoxidase in CKD patients. The apparent increase in RAGE levels by VDR activation reported in previous uncontrolled studies is most likely due to confounding factors rather than to VDR activation per se. This trial is registered with NCT01680198

Flexible electrode based on gold nanoparticles and reduced graphene oxide for uric acid detection using linear sweep voltammetry

In this work, an electrochemical sensor for uric acid determination is shown with a preliminary study for its validation in real samples (milk and urine). Uric acid can be electrochemically oxidized in aqueous solutions and thus it is possible to obtain electrochemical sensors for this chemical by means of this electrooxidation reaction. Indium tin oxide coated on flexible polyethylene terephthalate substrate, modified with reduced graphene oxide and gold nanoparticles by co-electrodeposition, was used. Electrodeposition was performed at -0.8V vs SCE for 200 s. All samples were characterized by electron scan microscopy and electron diffraction spectroscopy. A careful investigation on the effect of pH was performed to understand its influence on uric acid oxidation. The detection of uric acid was using the linear sweep voltammetry. Results show that the peak current increases linearly with uric acid concentration from 10 to 1000 μM with a limit of detection of about 7.1 μM. The sensor shows high selectivity towards different interferents that can be found in the milk and urine matrix, such as chloride, calcium, sodium and ammonium ions. To prove the applicability of the proposed sensor, uric acid was quantified in real milk and urine samples with excellent results comparable to those of conventional techniques

Monitoring Risk Factors and Improving Adherence to Therapy in Patients With Chronic Kidney Disease (Smit-CKD Project): Pilot Observational Study

Background: Chronic kidney disease is a major public health issue, with about 13% of the general adult population and 30% of the elderly affected. Patients in the last stage of this disease have an almost uniquely high risk of death and cardiovascular events, with reduced adherence to therapy representing an additional risk factor for cardiovascular morbidity and mortality. Considering the increased penetration of mobile phones, a mobile app could educate patients to autonomously monitor cardiorenal risk factors. Objective: With this background in mind, we developed an integrated system of a server and app with the aim of improving self-monitoring of cardiovascular and renal risk factors and adherence to therapy. Methods: The software infrastructure for both the Smit-CKD server and Smit-CKD app was developed using standard web-oriented development methodologies preferring open source tools when available. To make the Smit-CKD app suitable for Android and iOS, platforms that allow the development of a multiplatform app starting from a single source code were used. The integrated system was field tested with the help of 22 participants. User satisfaction and adherence to therapy were measured by questionnaires specifically designed for this study; regular use of the app was measured using the daily reports available on the platform. Results: The Smit-CKD app allows the monitoring of cardiorenal risk factors, such as blood pressure, weight, and blood glucose. Collected data are transmitted in real time to the referring general practitioner. In addition, special reminders improve adherence to the medication regimen. Via the Smit-CKD server, general practitioners can monitor the clinical status of their patients and their adherence to therapy. During the test phase, 73% (16/22) of subjects entered all the required data regularly and sent feedback on drug intake. After 6 months of use, the percentage of regular intake of medications rose from 64% (14/22) to 82% (18/22). Analysis of the evaluation questionnaires showed that both the app and server components were well accepted by the users. Conclusions: Our study demonstrated that a simple mobile app, created to self-monitor modifiable cardiorenal risk factors and adherence to therapy, is well tolerated by patients affected by chronic kidney disease. Further studies are required to clarify if the use of this integrated system will have long-term effects on therapy adherence and if self-monitoring of risk factors will improve clinical outcomes in this population

Converting from face-to-face to postal follow-up and its effects on participant retention, response rates and errors:lessons from the EQUAL study in the UK

Background: Prospective cohort studies are challenging to deliver, with one of the main difficulties lying in retention of participants. The need to socially distance during the COVID-19 pandemic has added to this challenge. The pre-COVID-19 adaptation of the European Quality (EQUAL) study in the UK to a remote form of follow-up for efficiency provides lessons for those who are considering changing their study design. Methods: The EQUAL study is an international prospective cohort study of patients ≥65 years of age with advanced chronic kidney disease. Initially, patients were invited to complete a questionnaire (SF-36, Dialysis Symptom Index and Renal Treatment Satisfaction Questionnaire) at research clinics every 3–6 months, known as “traditional follow-up” (TFU). In 2018, all living patients were invited to switch to “efficient follow-up” (EFU), which used an abbreviated questionnaire consisting of SF-12 and Dialysis Symptom Index. These were administered centrally by post. Response rates were calculated using returned questionnaires as a proportion of surviving invitees, and error rates presented as the average percentage of unanswered questions or unclear answers, of total questions in returned questionnaires. Response and error rates were calculated 6-monthly in TFU to allow comparisons with EFU. Results: Of the 504 patients initially recruited, 236 were still alive at the time of conversion to EFU; 111 of these (47%) consented to the change in follow-up. In those who consented, median TFU was 34 months, ranging from 0 to 42 months. Their response rates fell steadily from 88% (98/111) at month 0 of TFU, to 20% (3/15) at month 42. The response rate for the first EFU questionnaire was 60% (59/99) of those alive from TFU. With this improvement in response rates, the first EFU also lowered errors to baseline levels seen in early follow-up, after having almost trebled throughout traditional follow-up. Conclusions: Overall, this study demonstrates that administration of shorter follow-up questionnaires by post rather than in person does not negatively impact patient response or error rates. These results may be reassuring for researchers who are trying to limit face-to-face contact with patients during the COVID-19 pandemic