Double-blind Test Research Articles

Blinded Oral Challenges with Lactose and Placebo Accurately Diagnose Lactose Intolerance: A Real-Life Study.

Lactose intolerance (LI) is characterized by diarrhea, abdominal pain, or bloating occurring after lactose consumption in patients with lactose malabsorption. The National Institute of Health (NIH) proposed a double-blind placebo testing to identify LI individuals correctly. However, until now, no study used this approach in a real-life setting. We aimed to assess double-blind placebo challenge accuracy in diagnosing LI in patients with self-reported symptoms of LI. 148 patients with self-reported LI were consecutively enrolled and blindly underwent hydrogen breath test (HBT) after 25 g lactose or 1 g glucose (placebo) load. One week later, the subjects were challenged with the alternative substrate. Each subject completed a validated questionnaire, including five symptoms (diarrhea, abdominal pain, vomiting, bowel sounds, and bloating) scored on a 10-cm visual analog scale. Home questionnaire (HQ) referred to symptoms associated with the consumption of dairy products at home, while lactose questionnaire (LQ) and placebo questionnaire (PQ) referred to symptoms perceived throughout the 4-h after the administration of the substrates, respectively. After lactose load, HBT was positive in 81 patients (55%), of whom 60 (74%) reported relevant symptoms at LQ (lactose malabsorbers, LM). After placebo challenge, 45 out of 60 with a positive lactose challenge did not complain of symptoms and therefore were diagnosed as lactose intolerant, according to NIH definition. The blinded oral challenges with lactose and placebo accurately diagnose LI and identify patients who will likely benefit from a lactose-free diet.

Biosensor for Detecting Fetal Growth Restriction in a Low-Resource Setting

One strategy for improving detection of fetal growth restriction (FGR) is developing biosensors identifying placental dysfunction as a leading pathogenesis for FGR. The aim of this pilot study was to investigate the performance of a biosensor specified to detect placental dysfunction by means of maternal arterial turbulence acoustics in a low-resource setting. A cohort of 147 singleton pregnant women were prospectively followed with double-blinded biosensor tests, sonographic estimation of fetal weight (EFW) and Doppler flow at 26–28, 32–34 and 37–39 weeks of pregnancy. Full term live births with recorded birth weights (BWs) and without major congenital malformations were included. Outcomes were defined as (A) a solitary biometric measure (BW < 3rd centile) and as (B) a biometric measure and contributory functional measure (BW < 10th centile and antenatally detected umbilical artery pulsatility index > 95th centile). Data from 118 women and 262 antenatal examinations were included. Mean length of pregnancy was 40 weeks (SD ± 8 days), mean BW was 3008 g (SD ± 410 g). Outcome (A) was identified in seven (6%) pregnancies, whereas outcome (B) was identified in one (0.8%) pregnancy. The biosensor tested positive in five (4%) pregnancies. The predictive performance for outcome (A) was sensitivity = 0.29, specificity = 0.97, p = 0.02, positive predictive value (PPV) was 0.40 and negative predictive value (NPV) was 0.96. The predictive performance was higher for outcome (B) with sensitivity = 1.00, specificity = 0.97, p = 0.04, PPV = 0.20 and NPV = 1.00. Conclusively, these pilot-study results show future potential for biosensors as screening modality for FGR in a low-resource setting.

A Novel Molecular Method for Simultaneous Identification of Vibrio parahaemolyticus 57 K-Serogroups Using Probe Melting Curve Analysis.

The serotyping of Vibrio parahaemolyticus, which is crucial to the surveillance and detection of outbreaks of vibriosis infection, has been widely used in many countries. In this study, we developed a molecular assay, named multiplex ligation reaction based on probe melting curve analysis (MLMA), for simultaneous identification of V. parahaemolyticus 57 K-serogroups. Based on the previous genomes of 418 strains including 39 K-serogroups and the 18 K-serogroups sequences from public databases, we obtained 57 K-serogroups specific gene sequences for designing primers and probes. The developed MLMA assay for identifying the V. parahaemolyticus 57 K-serogroups showed high reproducibility, with the intra- and inter-assay standard deviations and coefficients of variation of no more than 1°C and 1%, respectively. The limit of detection for all gene targets ranged from 0.1 to 1.0 ng/µl. We validated the MLMA assay with a double-blind test identifying 595 V. parahaemolyticus isolates using conventional serotyping methods for comparison. The results showed the kappa value between the MLMA assay and the traditional serological method was 0.936 and that there was a 96.97% consistency rate with conventional serotyping methods for all detected isolates. Additionally, five rare K-serogroups were identified using the MLMA assay, as well as 18 strains that could not be identified using the traditional serotyping method. Thus, the MLMA assay provides a rapid, robust, and promising tool for the molecular serotyping of V. parahaemolyticus K-serogroups and has the potential application to the detection of outbreaks and surveillance of V. parahaemolyticus infection.

Deciphering big data in consumer credit evaluation

Abstract This paper examines the impact of large-scale alternative data on predicting consumer delinquency. Using a proprietary double-blinded test from a traditional lender, we find that the big data credit score predicts an individual’s likelihood of defaulting on a loan with 18.4% greater accuracy than the lender’s internal score. Moreover, the impact of the big data credit score is more significant when evaluating borrowers without public credit records. We also provide evidence that big data have the potential to correct financial misreporting.

Bitter Taste Receptors and Chronic Otitis Media.

To evaluate the presence of bitter taste receptors (T2Rs) in the middle ear and to examine their relationship with chronic ear infections. Cross-sectional study. Tertiary care hospital. This study enrolled 84 patients being evaluated for otologic surgery: 40 for chronic otitis media (COM) and 44 for other surgical procedures (controls). We collected a small piece of mucosa from 14 patients for mRNA analysis and from 23 patients for immunohistochemistry. A total of 55 patients underwent a double-blind taste test to gauge sensitivity to phenylthiocarbamide, denatonium, quinine, sucrose, and sodium chloride; 47 patients gave a salivary sample for single-nucleotide polymorphism analysis of rs1376251 (TAS2R50) and rs1726866 (TAS2R38). Bitter taste receptors were found in all samples, but the repertoire varied among patients. T2R50 was the most consistently identified receptor by mRNA analysis. Its rs1376251 allele was related to susceptibility to COM but not the expression pattern of T2R50. Ratings of bitterness intensity of phenylthiocarbamide, a ligand for T2R38, differed significantly between the COM and control groups. T2Rs were found within the middle ear of every patient sampled; the rs1376251 allele of TAS2R50 appears to be related to chronic ear infections. These receptors are an intriguing target for future research and possible drug targeting.

E-Nose Urine Analysis for Non-Invasive Diagnosis of Prostate Cancer: Focus on Data Processing for Drift Compensation

Even though the prostate cancer (KP) represents the fifth most common cancer in men worldwide, the current diagnostic protocol is affected by poor accuracy, which results in the un-detection of cancers and a high false positive rate causing patients’ overtreatment and a huge impact on healthcare spending.In recent years, many innovative approaches, proposing the characterization of biological fluids, especially urine, have been proposed in the scientific literature to improve current procedures. Among them, the most promising results have been obtained by means of the analysis of odours emanated from urine samples by electronic noses (EN). Those studies proved the existence of a specific correlation between urine odour alteration and KP presence that can be exploited to develop a novel, non-invasive and accurate diagnostic tool for the KP.However, no study has already led to the introduction of EN into the clinical practice, despite the high diagnostic accuracies reported (i.e., close or above 90%), which are considerably higher than the 58% achieved by current protocols. One of the main limitations is represented by the fact that no study addresses the problem of sensor drift. Drift, consisting in the deviation over time of sensor response under the same conditions, currently represents the primary obstacle to the scaling up of EN from research objects to effective diagnostic devices for large-scale use because of the progressive worsening over time of the classification performance and the consequent need for periodical recalibration of the system.For this reason, the present study, conceived within a research project proposing an EN for the non-invasive detection of KP, focuses on the description of the data processing protocol specifically developed for compensating drift. In particular, we here describe the adoption of the Orthogonal Signal Correction (OSC) algorithm to implement a drift correction model for a dataset acquired over 9 months, comprising urine headspaces from 122 subjects (81 KP patients and 41 control donors). The model proved effective in mitigating drift effects on 1-year old sensors by restoring their diagnostic accuracy from 55% up to about 80%, which was achieved by new sensors not subjected to drift issues. The developed model was validated by means of double-blind verification tests. The KP diagnosis model built on 1-year-old sensors achieved on double-blind samples an accuracy, sensitivity and specificity of 77% (CI 95% 60.7 - 88.9), 82% (CI 95% 59.7 - 94.8) and 71% (CI 95% 44.0 - 89.7), respectively, thereby confirming results achieved on training data.

Non-inferiority study of the efficacy of two hyaluronic acid products in post-extraction sockets of impacted third molars

BackgroundHyaluronic acid (HA) is well known to exert an anti-inflammatory effect during oral wound healing and is commonly applied after tooth extraction. However, no double-blind randomized controlled study comparing two hyaluronate mouthwash products has been conducted so far. The aim of this study was to comparatively analyze the efficacy of Mucobarrier® and Aloclair® in terms of clinical symptoms.ResultsA total of 112 patients were randomly assigned to assess the degree of discomfort, pain reduction, redness, burning sensation, and swelling between two groups on the day of surgery and 7 days later in a double blind test, with a total 56 Aloclair patients and 56 Mucobarrier patients. There was no statistically significant difference in the overall discomfort, degree of pain reduction, redness, burning sensation, and swelling between the Mucobarrier and Aloclair groups.ConclusionThe local application of hyaluronic acid mouth wash after wisdom tooth extraction is beneficial in reducing overall discomfort and pain reduction, and the clinical utility of Mucobarrier® is no different from Aloclair®.Trial registrationInstitutional Review Board of Yonsei University College of Dentistry, 2-2018-0036. Registered 10 September 2018—prospectively registered, https://eirb.yuhs.ac/

The diagnostic accuracy of isothermal nucleic acid point-of-care tests for human coronaviruses: A systematic review and meta-analysis

Many recent studies reported coronavirus point-of-care tests (POCTs) based on isothermal amplification. However, the performances of these tests have not been systematically evaluated. Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy was used as a guideline for conducting this systematic review. We searched peer-reviewed and preprint articles in PubMed, BioRxiv and MedRxiv up to 28 September 2020 to identify studies that provide data to calculate sensitivity, specificity and diagnostic odds ratio (DOR). Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) was applied for assessing quality of included studies and Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) was followed for reporting. We included 81 studies from 65 research articles on POCTs of SARS, MERS and COVID-19. Most studies had high risk of patient selection and index test bias but low risk in other domains. Diagnostic specificities were high (> 0.95) for included studies while sensitivities varied depending on type of assays and sample used. Most studies (n = 51) used reverse transcription loop-mediated isothermal amplification (RT-LAMP) to diagnose coronaviruses. RT-LAMP of RNA purified from COVID-19 patient samples had pooled sensitivity at 0.94 (95% CI: 0.90–0.96). RT-LAMP of crude samples had substantially lower sensitivity at 0.78 (95% CI: 0.65–0.87). Abbott ID Now performance was similar to RT-LAMP of crude samples. Diagnostic performances by CRISPR and RT-LAMP on purified RNA were similar. Other diagnostic platforms including RT- recombinase assisted amplification (RT-RAA) and SAMBA-II also offered high sensitivity (> 0.95). Future studies should focus on the use of un-bias patient cohorts, double-blinded index test and detection assays that do not require RNA extraction.

Using machine learning to develop an autoverification system in a clinical biochemistry laboratory.

Autoverification systems have greatly improved laboratory efficiency. However, the long-developed rule-based autoverfication models have limitations. The machine learning (ML) algorithm possesses unique advantages in the evaluation of large datasets. We investigated the utility of ML algorithms for developing an artificial intelligence (AI) autoverification system to support laboratory testing. The accuracy and efficiency of the algorithm model were also validated. Testing data, including 52 testing items with demographic information, were extracted from the laboratory information system and Roche Cobas® IT 3000 from June 1, 2018 to August 30, 2019. Two rounds of modeling were conducted to train different ML algorithms and test their abilities to distinguish invalid reports. Algorithms with the top three best performances were selected to form the finalized ensemble model. Double-blind testing between experienced laboratory personnel and the AI autoverification system was conducted, and the passing rate and false-negative rate (FNR) were documented. The working efficiency and workload reduction were also analyzed. The final AI system showed a 89.60% passing rate and 0.95 per mille FNR, in double-blind testing. The AI system lowered the number of invalid reports by approximately 80% compared to those evaluated by a rule-based engine, and therefore enhanced the working efficiency and reduced the workload in the biochemistry laboratory. We confirmed the feasibility of the ML algorithm for autoverification with high accuracy and efficiency.

The Effect of Moringa Oleifera Leaves Plus Royal Jelly Supplement on Cortisol Hormone and Stress Levels on Anemia of Pregnant Women in Takalar Regency

This study aims to determine the effect of Moringa Oleifera plus Royal Jelly leaf extract supplements on stress levels and cortisol levels in anemic pregnant women. This study was a true experimental study with a controlled randomized double blind pretest-post test design. The subjects of this study were 44 pregnant women with anemia, taken based on inclusion and exclusion criteria and divided into two groups, namely the group given moringa capsules (n = 22) and moringa capsules plus royal jelly (n = 22). Data were analyzed using Chi-square test, Paired T-Test, Wilcoxon and Independent T-Test using SPSS. The result of the study shows a significant decrease in the stress level in the royal jelly moringa group from 29.23 ± 10.451 to 17.00 ± 6.325 with a value of P = 0.000 and in the moringa group from 23.59 ± 8.110 to 18.05 ± 4.498 with a value of P = 0.022. Likewise, the cortisol levels decreased significantly in the moringa royal jelly group from 41.17 ± 18.466 to 28.75 ± 15.024 with a P value = 0.002 and the moringa group from 34.54 ± 21.437 to 24.70 ± 18.218 with a P value = 0.009. However, the difference in the magnitude of change did not differ significantly for stress levels and cortisol levels (P> 0.05). It is concluded that the reduction in stress and changes in royal jelly moringa tends to be greater than that of moringa.

The Trained Sniffer Dog Could Accurately Detect the Urine Samples from the Patients with Cervical Cancer, and Even Cervical Intraepithelial Neoplasia Grade 3: A Pilot Study.

Simple SummaryTumor detection by dog sniffing is a possible new method in cancer diagnosis. The aim of this study is to assess whether a trained dog can distinguish urine samples from cervical cancer patients. Urine samples were collected from 34 with cervical cancer, 49 patients with CIN3, 49 with benign uterine diseases, and 63 healthy volunteers. In all 83 test runs, one positive sample among five samples were presented to the dog. The trained dog accurately distinguished the urine sample of a cancer patient from those of the controls. This study showed that cancer detection by dog sniffing can be a non-invasive, cost-effective screening technique for cervical cancer.(1) Background: Previous reports have indicated that cancers of the stomach, lung, and pancreas can be detected by dog sniffing, but results have been varied. Here, a highly trained dog was used to determine whether urine from patients with cervical premalignant lesions and malignant tumors have a cancer-specific scent. (2) Methods: A total of 195 urine samples were collected from patients with cervical cancer, cervical intraepithelial neoplasia grade 3 (CIN3), benign uterine diseases, and healthy volunteers. Each test was performed using one urine sample from a cancer patient and four samples from different controls. Each of the five urine samples was placed in a separate box. When the cancer sniffing dog stopped and sat in front of the box with a sample from a cancer patient, the test was considered as positive. (3) Results: 83 patients with cervical cancer (34 cases of cervical cancer and 49 cases of cervical intraepithelial neoplasia grade 3), 49 patients with uterine benign diseases, and 63 healthy volunteers were enrolled, and their urine samples were collected. In 83 times out of 83 runs in a double-blind test, the trained dog could correctly identify urine samples of cervical cancer patients. (4) Conclusion: A trained dog could accurately distinguish the urine of all patients with cervical cancer or CIN3, regardless of the degree of cancer progression.

Effects of Pre-Workout Multi-Ingredient Supplement on Anaerobic Performance: Randomized Double-Blind Crossover Study.

Background: The purpose of this research was to investigate the acute effects of a pre-workout supplement on anaerobic performance in resistance-trained men. Methods: Twenty-three men underwent three randomized, double-blind testing sessions separated by a seven-day break. The participants performed three tests: isokinetic strength, three repetition maximum (3-RM) strength and Wingate. Statistical analysis was conducted in R environment. Linear mixed models were estimated via R package lme4. Results: Mean T@0.2 s was significantly greater in supplemented condition for right and left knee flexors (PL: 103.2 ± 37.6 Nm; supplemented condition: 131.8 ± 29.3 Nm (p = 0.001)), and PL: 103.7 ± 39.3; supplemented condition: 129.4 ± 28.4 (p = 0.001)). T@0.2 s for right and left knee extensors (PL: 202.6 ± 58.6 Nm; supplemented condition: 237.2 ± 54.7 Nm (p = 0.001); PL: 203.3 ± 63.2 Nm, supplemented condition: 229.8 ± 50.8 Nm (p = 0.002)). Significant difference was in mean anaerobic power between supplemented and PL condition for right and left knee flexors (p = 0.002, p = 0.005) and for right and left knee extensors (p = 0.001 and p = 0.002). TTP was significantly shorter in supplemented condition for both sides knee flexors (p = 0.002). There was a significant difference for mean power in the Wingate test (placebo: 8.5 ± 0.6 W/kg; supplemented condition: 8.7 ± 0.5 W/kg (p = 0.038)). Mean 3-RM was significantly greater in supplemented condition (p = 0.001). Conclusions: The supplement significantly improves upper and lower body strength and power output in resistance-trained men.

A randomized, double-blind water taste test to evaluate the equivalence of taste between tap water and filtered water in the Taipei metropolis

High water quality and sufficient water availability are the main concerns of water users. Promoting the efficient use of tap water can contribute to sustainable drinking water management and progress towards Sustainable Development Goals. In many metropolises, water suppliers treat municipal water with appropriate treatment processes and well-maintained distribution infrastructure. Under this circumstance, it is acceptable that municipal water can be a source of drinking water. The presence of residual chlorine in tap water, connected to municipal water supply, inactivates pathogenic microorganisms and prevents recontamination. However, adding chlorine to tap water may affect the organoleptic properties of drinking water. On the other hand, the use of point-of-use (POU) water dispensers, which provides an additional treatment step on tap water, is not energy-efficient. A randomized, double-blind water taste test was conducted in the Taipei metropolis to assess whether tap water from public drinking fountains and filtered water from POU water dispensers have similar organoleptic properties. An odds ratio (OR) and the area under the receiver operating characteristic curve (AUC) were used to measure the participants’ ability to distinguish between the two water varieties. A five-region hypothesis test was conducted to test the OR, and a 95% bootstrap confidence interval of the AUC was calculated. The results of the study showed that the 95% five-region confidence interval of OR equal to (0.5, 1.49), and the 95% bootstrap confidence interval of AUC equal to (0.42, 0.56). These results implied that people in the Taipei metropolis could not distinguish between tap water and filtered water. It is recommended that more drinking fountains be installed and maintained fully functional and clean to achieve excellence in tap water access.

Post-marketing pharmaco-economics evaluation of Jinye Baidu Granules

To evaluate the economy and applicability of Jinye Baidu Granules in the treatment of acute upper respiratory tract infection, a randomized, double-blind, positive drug parallel control clinical trial was conducted in this study. Stratified block random, double-blind and double simulation test was used. The experimental group took Jinye Baidu Granules, 10 g/time, three times a day, and Compound Shuanghua Granules placebo, 6 g/time, four times a day. The control group took Compound Shuanghua Granules, 6 g/time, 4 times a day, and Jinye Baidu Granules placebo, 10 g/time, 3 times a day. The course of treatment was 5 days. The total cost of this study included direct medical cost and indirect medical cost. The incremental cost-effect analysis method was used for evaluation. Treeage Pro software was used to build a pharmaco-economics model and make statistical analysis. Patients from 10 hospitals were divided into experimental group(304 cases) and control group(302 cases). The baseline values of age, sex ratio, clinical symptoms and signs scores, and important physical examination indexes of the two groups were compared. After 5 days of treatment, the cost per capita of the experimental group was(388.06±94.17) Yuan, and that of the control group was(378.47±95.46) Yuan. The cost of direct medical treatment per capita was(271.24±54.11) Yuan for the experimental group and(264.88±112.71) Yuan for the control group. The average cost of indirect medical treatment was(116.82±82.75) Yuan in the experimental group and(113.59±87.77) Yuan in the control group, with no significant difference in the cost of medical treatment per capita, the cost of direct medical treatment per capita and the cost of indirect medical treatment per capita between both groups. The results of incremental cost-effect analysis based on the total score difference in symptoms and signs after 5 days of treatment showed that ICER=23.39 Yuan/score, which was less than the willingness to pay 100 Yuan/score determined through expert interviews. The experimental group had economic advantages over the experimental group, with the economic probability of 53%. Sensitivity analysis supported the robustness of the results. The results of incremental cost-effect analysis based on the total recovery rate of symptoms and signs showed that compared with the experimental group, the control group had lower cost, better effect and absolute economic advantage, with a corresponding probability of 55%. Based on the above results, it is concluded that there is no significant difference in economic outcome between Jinye Baidu Gra-nules and Compound Shuanghua Granules in the treatment of acute upper respiratory tract infection.

The First Human Clinical Trial on the Skin Depigmentation Efficacy of Glycinamide Hydrochloride

A previous study identified certain low molecular anti-melanogenic peptides that share a common sequence with α-melanocyte stimulating hormone (MSH) and end with a glycinamide moiety. Glycinamide itself also showed anti-melanogenic activity in cell-based assays, but neither glycine nor acetyl glycinamide were active, which indicated a special structure and activity relationship. The aim of this study was to examine the skin depigmentation efficacy of glycinamide hydrochloride in human subjects. The primary skin irritation potential of glycinamide hydrochloride was evaluated by patch testing in 30 human subjects. The skin depigmentation efficacy of glycinamide hydrochloride was evaluated in a double-blinded clinical test in 21 human subjects. The test product and a control product were applied to designated sites on the right or left side of the face twice daily for eight weeks. Skin color parameters, i.e., the melanin index, the L* value (representing skin lightness), a* value (redness), and b* value (yellowness) were measured using instruments. The individual topology angle (ITAo, representing skin color) was calculated from L* and b values. The degree of skin pigmentation was visually assessed by two testers. The primary skin irritation test showed that a solution containing glycinamide hydrochloride up to 10% did not induce any adverse skin responses. In the efficacy test, the test product significantly reduced the melanin index, and increased L* value and ITAo after two weeks of application relative to the baseline value at the start of the test. It also significantly lowered the degree of pigmentation after 6 weeks of application, relative to the baseline value. Differences in the melanin index, L* value, ITAo and the degree of pigmentation between the test and control groups became statistically significant after six weeks or eight weeks of application. No signs of skin irritation were observed during the efficacy test. The present study suggests that glycinamide hydrochloride has great potential to be used in the control of skin hyperpigmentation.

Efficacy and safety of oral immunotherapy with AR101 in European children with a peanut allergy (ARTEMIS): a multicentre, double-blind, randomised, placebo-controlled phase 3 trial

Peanut allergy is the leading cause of food-related anaphylaxis. Current management options can negatively affect food allergy-related quality of life. We aimed to investigate the efficacy of an investigational oral biologic drug (AR101). The AR101 Trial in Europe Measuring Oral Immunotherapy Success in peanut-allergic children (ARTEMIS) trial was a multicentre, double-blind, randomised, placebo-controlled phase 3 trial done at 18 hospitals in Ireland, France, Germany, Italy, Spain, Sweden, and the UK. Children and adolescents with peanut allergy, aged 4-17 years, who developed dose-limiting symptoms to 300 mg or less peanut protein (equivalent to approximately one peanut kernel) during a double-blind placebo-controlled food challenge test at study entry were enrolled. Participants were randomly assigned (3:1) to receive daily doses of either AR101 oral immunotherapy (AR101 group) or a taste-masked placebo (placebo group). All participants, investigators, and care providers were masked to treatment allocation until the study was completed. Doses were increased every 2 weeks over 6 months until a dose of 300 mg was reached and maintained for 3 months. The primary endpoint was the proportion of participants in the intention-to-treat or safety population (defined as those participants who had been randomly assigned and had received at least one dose of the assigned drug) who could consume a single dose of 1000 mg (cumulative dose 2043 mg) peanut protein without developing dose-limiting allergic symptoms at an exit double-blind placebo-controlled food challenge after 9 months of treatment. Additional endpoints included safety (ie, the frequency and severity of adverse events) and changes in food allergy-related quality of life, assessed by use of age-appropriate Food Allergy Quality of Life Questionnaires (FAQLQs) and the Food Allergy Independent Measure (FAIM). The study is registered with ClinicalTrials.gov, NCT03201003, and is completed. Between June 12, 2017, and Feb 15, 2018, 227 patients were screened, of whom 175 were randomly assigned to the AR101 group (n=132) and the placebo group (n=43). All primary and secondary endpoints were met. 77 (58%) of 132 participants in the AR101 group tolerated 1000 mg peanut protein at the exit food challenge versus one (2%) of 43 participants in the placebo group (AR101-placebo treatment difference 56·0% [95% CI 44·1-65·2], p<0·0001). Adverse events were reported by almost all participants. The maximum severity of adverse events reported was mild or moderate for most participants who received AR101 (mild, 66 [50%] of 132 participants; moderate, 63 [48%]; and severe, one [1%]) or placebo (mild, 24 [56%] of 43 participants; moderate, 18 [42%]; severe, none). Participants aged 8-12 years in the AR101 group reported improvements that exceeded the minimum clinically important difference between the two groups across all FAQLQ domains. Additionally, participants in the AR101 group and their caregivers reported improvements that exceeded the minimum clinically important difference in FAIM domains related to the perceived likelihood and outcomes of a severe allergic reaction. AR101 oral immunotherapy treatment led to rapid desensitisation to peanut protein, with a predictable safety profile that improved with treatment, and an associated improvement in self-reported and caregiver-reported food allergy-related quality of life. These patient-oriented outcomes provide invaluable data to help physicians, patients, and caregivers make informed, shared decisions on the management of peanut allergy. Aimmune Therapeutics.

Fluorescence spectroscopy on paraffin-preserved human liver samples to classify several grades of fibrosis.

Nowadays, it is well established that biopsy is the gold standard for medical diagnosis of liver disease; however, recent studies have shown numerous discrepancies in biopsy assessment, even when it is evaluated by senior pathologists. Fluorescence spectroscopy is a tool that has been of utility in the diagnosis of different diseases based on biopsy analysis. Thus, fluorescence study of liver samples with five different degrees of fibrosis is presented. Paraffin-preserved human liver tissue was provided on white plastic cassettes by the Hospital General de Mexico "Dr. Eduardo Liceaga". Specimens were diagnosed by two independent-senior pathologists in a double-blind test and classified into five different groups: F0, F1, F2, F3, and F4, according to the METAVIR scale for liver fibrosis. Fluorescence spectroscopy measurements were performed using three different excitation wavelengths: 385, 405, and 450nm. Besides, diffuse reflectance spectroscopy (DRS) measurements were taken with white light to determine morphological changes in the tissue and to compare the results with medical diagnosis. The spectral analysis at excitation wavelengths of 385nm and 405nm showed poor correlation with medical diagnosis. Likewise, in order to discard all possible error-sources involved in the measurements, an exhaustive study was carried out; it included the determination of the fluorescence noise produced by paraffin, cassette, and the tissue itself. At 450nm excitation wavelength, no fluorescence by the cassette was detected and noise-subtraction methods were not required, this allows a high correlation of hepatic fibrosis stages between pathological diagnosis and spectroscopic analysis. For this excitation wavelength, 89.87% correlation with DRS measurements and 82.00% with medical diagnosis were obtained. This work demonstrates that fluorescence spectroscopy using 450nm excitation wavelength might work as a complementary tool to grade hepatic fibrosis in human liver specimens.

Adherence to study drug in a stroke prevention trial"?>

ObjectiveStandards for reporting and analyzing adherence to medical therapy have recently improved due to international consensus efforts. If applied to clinical trial research in patients with stroke, these improvements have the potential to identify when in the sequence of trial operations participants are at risk for non-adherence and opportunities to safeguard adherence. MethodsWe analyzed three phases of adherence according to the European Society for Patient Adherence, COMpliance, and Persistence (ESPACOMP) Medication Adherence Reporting Guideline (EMERGE) taxonomy in the Insulin Resistance Intervention after Stroke (IRIS) trial: initiation (did patient start drug), implementation (did patient take a drug holiday, defined as temporary cessation lasting ≥14 days), and persistence (did patient prematurely and permanently discontinue drug). IRIS was a randomized, placebo controlled, double-blind trial testing pioglitazone to prevent stroke or myocardial infarction in patients with a recent ischemic stroke or transient ischemic attack. Adherence was classified by self-report. Researchers used coaching algorithms to seek adherence recovery if participants went off drug. ResultsDuring 2005-2013, 3876 participants were enrolled from 179 sites in seven countries and followed for a mean of 4.8 years. Less than 1% of participants in each group did not initiate study drug. 20% of patients assigned to pioglitazone and 17% assigned to placebo took at least one drug holiday. 36% and 30%, respectively, discontinued the study drug prematurely with or without a prior holiday. The risk for stopping the study drug (temporarily or permanently) in the first year after randomization was twice the risk in each of the subsequent four years. This was true both for patients assigned to active therapy and placebo. More participants assigned to pioglitazone, compared to placebo, took a drug holiday or permanently stopped study drug, but the difference in rates of discontinuation was only evident in year one. In years two through five, rates of discontinuation were similar in the two treatment groups. The difference in rates during year one was the result of adverse effects related to the active study drug, pioglitazone. During the remainder of the trial, the attribution of discontinuations to adverse effects potentially related to pioglitazone was reduced but still higher in those assigned to active drug. Other reasons for discontinuation were similar between treatment groups and were largely unrelated to pharmacodynamic effects of the study drug. Rates of discontinuation varied widely among research sites. ConclusionPatients in a drug trial for stroke prevention are at greatest risk for premature drug discontinuation early after randomization. Reasons for discontinuation change over time. Variable discontinuation rates among sites suggests that adherence can be improved by using best practices from high-performing sites.

An Investigation of the Skin Barrier Restoring Effects of a Cream and Lotion Containing Ceramides in a Multi-vesicular Emulsion in People with Dry, Eczema-Prone, Skin: The RESTORE Study Phase1.

IntroductionThe replenishment of skin lipids depleted in the dry skin state is a desirable therapeutic target to restore skin moisturization; however, there is limited evidence demonstrating the success of this approach through the use of topical emollients. The purpose of this study was to provide evidence of the benefits of a cream and equivalent lotion containing skin lipids in a multi-vesicular emulsion for the management of dry skin. The hypothesis was that the test cream and test lotion could sustain skin moisturization for longer than traditional emollients by sustainably delivering skin lipids.MethodsA double-blind intra-subject vehicle-controlled single open-application test on the lower legs in people with dry, atopic dermatitis (atopic eczema)-prone, skin was conducted. There were six treatment sites, three per lower leg in each participant, which were treated with the test cream, the test lotion, three reference creams commonly prescribed in the UK and no treatment as a control. After baseline measurements of skin hydration, 100 μl of the test/reference creams was applied to each of the relevant treatment sites (random site allocation). Following treatment, measurements of skin hydration and scoring of visual dryness was conducted at timed intervals (3, 6, 12 and 24 h post-product application).ResultsThe test cream and lotion both significantly increased skin hydration and reduced skin dryness for at least 24 h following a single application compared to a no treatment control site. Compared to three reference emollient creams the test cream and test lotion were the only products capable of sustaining clinically meaningful improvements in skin moisturization for 24 h.ConclusionThe sustained moisturization imparted by the test products reduces the need for frequent emollient application, often requiring 3–4 applications per day for traditional emollients, and should reduce the high burden of managing dry skin conditions like atopic dermatitis.

Sensory aspects of acceptability of bitter-flavoured 7.5mm film-coated tablets in adults, preschool and school children.

There is great interest in demonstrating acceptability of solid oral formulations in paediatric populations. This study investigated the acceptability of small, 7.5mm, bitter-flavoured, coated tablets in healthy children and adults. A randomised, double-blind acceptability test was performed involving 101 children (4-12years) and 52 adults (18-75years). Acceptability was measured by participants as sensory assessment of taste, mouthfeel and hedonic perception, and by researcher observations of ability to swallow the tablet and negative facial expressions. Additionally, the taste-masking effect of film coatings was assessed based on the intensity of bitterness perception. At least one tablet was voluntarily swallowed by 35.7% of 4-6-year olds, 74% of 7-12-year olds and 98% of adults. The bitterness of the tablet did not affect participants' ability to swallow it. The sensory properties determined whether the tablet was acceptable. The following factors: low bitterness, high smoothness, high slipperiness and pleasant aftertaste had a positive impact on overall palatability in both populations. The paediatric scores during sensory evaluation of tablets differed from adults, showing lower acceptability. This study demonstrates the multifactorial nature of palatability of tablets and highlights that adults' palatability evaluation cannot be directly translated to a paediatric population.