Short-term Trials Research Articles

Wearable Real-Time Haptic Biofeedback Foot Progression Angle Gait Modification to Assess Short-Term Retention and Cognitive Demand.

Foot progression angle gait (FPA) modification is an important part of rehabilitation for a variety of neuromuscular and musculoskeletal diseases. While wearable haptic biofeedback could enable FPA gait modification for more widespread use than traditional tethered, laboratory-based approaches, retention, and cognitive demand in FPA gait modification via wearable haptic biofeedback are currently unknown and may be important to real-life implementation. Thus, the purpose of this study was to assess the feasibility of wearable haptic biofeedback to assess short-term retention and cognitive demand during FPA gait modification. Ten healthy participants performed toe-in (target 10 degrees change in internal rotation) and toe-out (target 10 degrees change in external rotation) haptic gait training trials followed by short-term retention trials, and cognitive multitasking trials. Results showed that participants were able to initially respond to the wearable haptic feedback to modify their FPA to adopt the new toe-in (9.7 ± 0.8 degree change in internal rotation) and toe-out (8.9 ± 1.0 degree change in external rotation) gait patterns. Participants retained the modified gait pattern on average within 3.9 ± 3.6 deg of the final haptic gait training FPA values. Furthermore, cognitive multitasking did not influence short-term retention in that there were no differences in gait performance during retention trials with or without cognitive multitasking. These results demonstrate that wearable haptic biofeedback can be used to assess short-term retention and cognitive demand during FPA gait modification without the need for traditional, tethered systems.

Can Green Tea Alleviate the Effects of Stress Related to Learning and Long-Term Memory in the Great Pond Snail (Lymnaea stagnalis)?

Stress and anxiety have become more prevalent issues in recent years and teenagers are especially at high risk. Recent studies show that experiencing stress while learning can impair brain-cell communication, thus inhibiting learning. Green tea is believed to have the opposite effect, aiding in learning and memory retention. Lymnaea stagnalis is a pond snail with a simple nervous system and easily observable behaviors, making it an excellent model organism for human neurobiology. In this study, we used L. stagnalis to explore the relationship between green tea and a stressor that impairs memory formation to determine the effects of both green tea and stress on the snails’ ability to learn, form, and retain memories. Memory was assessed using a conditioning procedure known as conditioned taste aversion (CTA), where snails are exposed to a sweet substance followed by a bitter taste with the number of biting responses being recorded. For the CTA groups, a total of 33 snails in 3 separate cohorts (Control (i.e. no stress), stressed, and stressed with green tea) was used in the trainings. Our results indicated that the best learning and memory occurred in the combination stressed with green tea group, specifically for long-term memory, although snails displayed good learning and memory during the short-term and intermediate trials. Stress was shown to be harmful to snail learning and memory for short-term, intermediate, and long-term memory. Thus, green tea not only alleviated the effects of stress, but also improved the snails’ ability to learn and remember compared to their control counterparts (not stressed) group.

Preface

International scientific conference “World Technological Trends in Agribusiness (WTTA 2020)” was held at Omsk State Agrarian University, Omsk, Russia on 4-5 July 2020. WTTA 2020 aimed to develop the scientific cooperation between Russian and international researchers in the field of agrotechnologies.The conference has become an agriculture forum for researchers, practitioners and scholars to discuss the most recent developments in agroengineering, agriculture and melioration. The participants have presented innovative engineering solutions for automated crop production and cattle breeding. A range of technological advances for treatment, processing, and storage of vegetal raw materials and livestock products has been presented. Environmentally-friendly agricultural solutions turned out to be quite a topical issue to explore.There were more than 300 papers submitted for publication. After the reviewing process, 270 of them were selected and approved for publication in the WTTA 2020 proceedings. Due to the Covid-19 pandemic, the conference was held in a mixed format. Most of the participants took part in presentia, at the same time, about 60 people made presentations via videoconferencing.Virtual participation was organized using the Zoom platform. Remote technologies made it possible to make presentations for participants from Stavropol State Agrarian University, Federal Research Centre of Biological Systems and Agrotechnologies (RAS, Orenburg), Altai State University, Mari State University, Krasnoyarsk Research Center (RAS, Krasnoyarsk), Ingush Agricultural Research Institute, etc.Links for participation in virtual meetings were sent round by the speakers freely. Sending invitations to colleagues was encouraged. Registration of listeners was not carried out, as a result, it was not possible to accurately estimate their number. Nevertheless, according to the organizing committee’s estimates, at least 30 listeners attended the conference sessions. Among them were employees of the Belarusian State University, Tashkent Institute of Irrigation and Agricultural Mechanization Engineers, and Kazakh National Agrarian University.At the time of the conference, Omsk State Agrarian University did not use the Zoom platform as the main tool for organizing distance education. In this regard, Zoom was used as a short-term trial period, which determined the tight timing of the main conference meetings.During the conference, five conference rooms equipped for videoconferencing were used. A special group of volunteer moderators was created to ensure the integrity of discussion and involvement of both local and virtual participants. The main task for the moderators was to repeat the audience’s questions to the virtual participants. Besides, they provided the right to a voice question to registered participants and read questions from listeners sent to the chat.Holding the conference in such format has become a new and valuable experience for the entire team of organizers. This experience was successful thanks to the participation of the university administration, student volunteers and assistance from the client department of the Zoom platform. At last, we would like to express our gratitude to the editorial team and reviewers as well as to the conference organizers. We are glad that, despite all the challenges associated with the coronavirus pandemic, we were able to collect and review the papers and prepare the WTTA 2020 proceedings.

Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes

BackgroundFinerenone, a nonsteroidal, selective mineralocorticoid receptor antagonist, reduced albuminuria in short-term trials involving patients with chronic kidney disease (CKD) and type 2 diabetes. However, its long-term effects on kidney and cardiovascular outcomes are unknown.MethodsIn this double-blind trial, we randomly assigned 5734 patients with CKD and type 2 diabetes in a 1:1 ratio to receive finerenone or placebo. Eligible patients had a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 30 to less than 300, an estimated glomerular filtration rate (eGFR) of 25 to less than 60 ml per minute per 1.73 m2 of body-surface area, and diabetic retinopathy, or they had a urinary albumin-to-creatinine ratio of 300 to 5000 and an eGFR of 25 to less than 75 ml per minute per 1.73 m2. All the patients were treated with renin–angiotensin system blockade that had been adjusted before randomization to the maximum dose on the manufacturer’s label that did not cause unacceptable side effects. The primary composite outcome, assessed in a time-to-event analysis, was kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes. The key secondary composite outcome, also assessed in a time-to-event analysis, was death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure.ResultsDuring a median follow-up of 2.6 years, a primary outcome event occurred in 504 of 2833 patients (17.8%) in the finerenone group and 600 of 2841 patients (21.1%) in the placebo group (hazard ratio, 0.82; 95% confidence interval [CI], 0.73 to 0.93; P=0.001). A key secondary outcome event occurred in 367 patients (13.0%) and 420 patients (14.8%) in the respective groups (hazard ratio, 0.86; 95% CI, 0.75 to 0.99; P=0.03). Overall, the frequency of adverse events was similar in the two groups. The incidence of hyperkalemia-related discontinuation of the trial regimen was higher with finerenone than with placebo (2.3% and 0.9%, respectively).ConclusionsIn patients with CKD and type 2 diabetes, treatment with finerenone resulted in lower risks of CKD progression and cardiovascular events than placebo. (Funded by Bayer; FIDELIO-DKD ClinicalTrials.gov number, NCT02540993.)

An Interactive Smartphone App, Nenne Navi, for Improving Children's Sleep: Pilot Usability Study.

BackgroundHealthy sleep is important not only for physical health but also for brain development in children. Several reports have revealed that Japanese adults and children have later bedtimes and shorter sleep durations compared with those in other countries, possibly because of Japanese culture and lifestyles. Therefore, an intervention tool that is suitable to the Japanese sociocultural environment is urgently needed to improve children’s sleep problems in their early years.ObjectiveTo provide appropriate sleep health literacy to caregivers and change their parenting behavior, we developed a smartphone app that allows reciprocal interaction between caregivers and pediatric sleep experts. This paper describes a preliminary study to examine the app’s basic design and functions and to establish its acceptability and usability in a small sample.MethodsA total of 10 caregivers and 10 infants (aged 18-28 months; 4/10, 40% boys) living in Japan participated in the study. At the start of the trial, the e-learning content regarding sleep health literacy was delivered via a smartphone. Thereafter, caregivers manually inputted recorded data about their own and their infant’s sleep habits for 8 consecutive days per month for 2 months. After pediatric sleep experts retrieved this information from the Osaka University server, they specified the problems and provided multiple sleep habit improvement suggestions to caregivers. Caregivers then selected one of the feasible pieces of advice to practice and reported their child’s sleep-related behaviors via the app. Actigraphy was used to monitor children’s sleep behaviors objectively. The concordance between the information provided by caregivers and the actigraphy data was assessed. The acceptability and usability of the app were evaluated using self-report questionnaires completed by caregivers; qualitative feedback was obtained via semistructured interviews after the intervention.ResultsThere was no significant difference between the information provided by the caregivers and the actigraphy data for bedtimes and wake-up times (P=.13 to P=.97). However, there was a difference between the actigraphy data and the caregivers’ reports of nighttime sleep duration and nighttime awakenings (P<.001 each), similar to prior findings. User feedback showed that 6 and 5 of the 10 caregivers rated the app easy to understand and easy to continue to use, respectively. Additionally, 6 of the 10 caregivers rated the app’s operativity as satisfactory. Although this was a short-term trial, children’s sleep habits, caregivers’ sleep health consciousness, and parenting behaviors improved to some extent.ConclusionsThe present findings suggest that the app can easily be used and is acceptable by Japanese caregivers. Given the user feedback, the app has the potential to improve children’s sleep habits by sending individualized advice that fits families’ backgrounds and home lives. Further studies are needed to confirm the efficacy of the app and facilitate social implementation.

PCN265 Assessment of Different Methods for the Extrapolation of Survival Statistics for Nivolumab in Metastatic Melanoma: Implications for Cost-Effectiveness in HTA

Extrapolation of immature overall survival (OS) or progression-free survival (PFS) trial data using standard parametric (SP) models based on prior distributions (e.g. Exponential, Weibull, Gompertz) is commonly used for economic modelling in HTA. Due to complex hazard functions, SP models may produce a poor fit for OS and PFS for immuno-oncology (I-O) treatments. This project aims to compare SP models with cubic spline (CS) methods, to assess the impact of extrapolation methods on estimated cost-effectiveness of nivolumab compared to dacarbazine in metastatic melanoma. OS and PFS data were extracted from digitised Kaplan-Meier curves reported in the CheckMate 066 trial. SP and CS models were fitted to two data cut-offs at 16 and 52 months to assess the effect of different follow-up periods on model choice. Incremental cost-effectiveness ratios (ICERs) per QALY gained were estimated using a partitioned survival model with a lifetime horizon. ICERs for nivolumab vs. dacarbazine were similar for SP and CS models fitted to the 16-month data cut-off (£23,244, £24,026). Based on the 52-month cut-off, nivolumab was more cost-effective based on SP fit compared to CS (£22,269 vs. £34,850). CS models were a better fit to the KM data based on visual inspection. The choice of distribution for SP model of nivolumab 16-month OS presented a wide range of ICER estimates (£13,753-52,466). The Gompertz SP model often presented the lowest AIC, but also resulted in a significantly different predicted survival (and thus lower ICER) compared to other distributions. The choice of statistical fit in SP models had a large impact on lifetime ICER with short-term trial data. Both models provided a good fit for the plateau in OS using the long data cut-off. CS models provide a robust fit and less uncertainty for HTA in the absence of long-term survival endpoints for I-O treatments.

SCN2A-Developmental and Epileptic Encephalopathies: Challenges to trial-readiness for non-seizure outcomes.

SCN2A-associated developmental and epileptic encephalopathies (DEEs) present with seizures, developmental impairments, and often both. We sought to characterize the level and pattern of development in children with SCN2A variants, and to address the sensitivity of the Vineland Adaptive Behavior Scales (VABS) in measuring changes over time in children with SCN2A-DEEs. Clinical histories for participants with pathogenic SCN2A variants in the Simons SearchLight project were analyzed for descriptive purposes. VABS scores obtained at study entry and yearly thereafter were analyzed for floor and ceiling effects, change with age, and association with epilepsy through use of regression and longitudinal regression methods. Sixty-four participants (50 with epilepsy, 30 [47%] female, median age 49months, interquartile range [IQR] 28 to 101) were included. Histories of birth complications (N=34, 54%), neonatal neurological signs (N=45, 74%), and other neurological symptoms (N=31, 48%) were common and similar in epilepsy and nonepilepsy subgroups. Mean standardized VABS scores (Composite 53.5; Motor, 55.8, Communication, 54.1, Socialization, 59.4, and Daily living skills, 55.1) reflected performance ~3 standard deviations below the normative test average. In longitudinal regression analyses, standardized scores decreased between 1.3 and 2.8 points per year, suggesting regression of abilities. Raw score analyses, however, revealed several subdomains with substantial floor effects (eg, community use); other raw scores increased with increasing age. Participants with epilepsy scored 0.6 to 1 SD lower than those without epilepsy (all P's<.05). The VABS, as standardly administered, has shortcomings for addressing growth or regression in individuals with SCN2A-DEEs. Some subdomain raw scores reflected substantial floor effects. Raw scores increased so slowly over time that standardized scores declined. Alternative measures sensitive to incremental meaningful change are required if outcomes such as adaptive behavior are to be primary outcomes in short-term clinical trials.

Long-Term IaaS Selection Using Performance Discovery

We propose a novel framework to select IaaS providers according to a consumer’s long-term performance requirements. The proposed framework leverages free short-term trials to discover the unknown QoS performance of IaaS providers. We design a temporal skyline-based filtering method to select candidate IaaS providers for the short-term trials. A novel cooperative long-term QoS prediction approach is developed that utilizes past trial experiences of similar consumers using a workload replay technique. We propose a new trial workload generation model that estimates a provider’s long-term performance in the absence of past trial experiences. The confidence of the prediction is measured based on the trial experience of the consumer. A set of experiments are conducted based on real-world datasets to evaluate the proposed framework.

Long-term dietary diludine (diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate) intake and gamete storage affect α-tocopherol status and reproductive performance in female rainbow trout, Oncorhynchus mykiss

Rainbow trout broodstocks were fed diets with varying levels of diludine [0 (D0; control), 0.25 (D1), 0.5 (D2) and 1 g kg−1 (D3)] during 2 consecutive reproduction seasons. Fish were started to be fed 3 months before spawning for the first reproduction season and they were kept on the same diets as well as an additional dietary group with 3 g kg−1 dietary diludine (D4) until the following reproduction season, providing short and long-term dietary treatments. Gametes storage at 6 °C for four and fifteen days prior to the fertilization in the first and second reproduction season, respectively, was also tested. Short-term feeding trial did not influence reproductive performance when the eggs were fertilized immediately after stripping, whereas survival at eyed-stage embryos significantly decreased in eggs, from fish fed diludine free diet, fertilized after 4-day storage. Dietary diludine level corresponded with increasing level of vitamin E in the eggs, which positively correlated with survival at eyed-stage embryos from the eggs with or without 15-day storage after long-term feeding. Fish fed the diet with highest level of diludine (D4) produced eggs higher in number but smaller in size in comparison to those from the other four experimental groups. In eggs fertilized after 15-day storage, survival rate was 20-fold higher in D4 diet fed fish in comparison to the other experimental groups. Our overall results indicate that dietary diludine has vitamin E sparing effect in the eggs and protects gamete viability during the storage when it is provided at 3 mg kg−1 dietary level, which result in lower lipid peroxidation and higher reproductive performance.

Immunomodulatory Effect of Sodium Saccharin and Potassium Acesulfame in BALB/C Mice in Short-Term Trials

Introduction: Sweeteners are molecules that give a sweet taste to a foodstuff. The question of the correct use of sweeteners is still being studied because the results of investigations are often contradictory.&#x0D; Objective: the current study aims at evaluating the risk of short-term immunotoxicity induced by sodium saccharin and potassium acesulfame in BALB/c mice.&#x0D; Methods: Animals are given low concentrations of sweeteners (0%, 0.5%, 1%, 2%) in drinking water for 90 days. During this period, a subcutaneous immunization is conducted. Blood is taken from the retro-orbital sinus and the animals are sacrificed by cervical dislocation. Weight measurements and histological studies have involved spleen, thymus, bladder and lungs. Levels of immunoglobulins are measured by reversed single radial immunodiffusion.&#x0D; Results: A significant rise in the consumption of sweeteners is found in the groups receiving doses of 1% and 2% (p&lt;0.05). Organ weight is not affected in both sexes (p&gt;0.05). Histology shows no tissue abnormality of thymus and lungs in groups consuming sweeteners. However, histological disturbances of the spleen are observed in mice that have received the dose of 2%. Histological study of bladder has revealed hyperplasia in the groups receiving 1% and 2% of sweeteners. Immunodiffusion assay shows no change in immunoglobulin levels in the groups consuming sweeteners (p&gt;0.05).&#x0D; Conclusion: Sweeteners have adverse effects on the immune system in BALB/c mice and induce histological abnormalities in the spleen and bladder.&#x0D; Keywords: Sweeteners, Saccharin, Potassium Acesulfame, Immunotoxicity, Immunoglobulins, Reversed single Radial Immunodiffusion.

The Treatment of Topical Drugs for Postherpetic Neuralgia: A Network Meta-Analysis

Background (PHN) is a neuropathic pain that causes a reduction in patients' quality of life. There are many drugs for PHN, including lidocaine patch, application of capsaicin, and others. Objectives This study aims to compare the efficacy and safety of drugs for PHN. Study design Relevant studies were found by systemically searching for terms including topical and Postherpetic neuralgia in PubMed, Cochrane library, MEDLINE, and EMBASE databases (inception through June 12, 2019). The primary outcome was the percentage of change in the Numeric Rating Scale or the Visual Analog Scale scores from baseline. The secondary outcome was the number of adverse events. Methods The efficacy and safety of drugs for PHN was investigated by the pairwise meta-analysis and Bayesian network meta-analysis, applying Revman 5.3, the Stata 14.0 software, and GeMTC 0.14.3. Results Twelve studies met the inclusion criteria, and eligible studies were selected for the ultimate meta-analysis. Our meta-analysis displayed 6 drugs for PHN. Lidocaine, high-concentration capsaicin, and aspirin/diethyl ether (ADE) had a higher possibility of bringing pain relief than placebo. Among them, lidocaine had the highest possibility of being the most effective drug for PHN and had the statistical significances compared with diclofenac, high-concentration capsaicin, indomethacin, low-concentration capsaicin, and placebo, and lidocaine was significantly preferable than other effective drugs in the aspect of safety. Limitations (1) The small number of included studies; (2) a small number of patients and short-term trials in progress, including lidocaine and ADE; (3) both randomized controlled trial and crossover randomized trial were included in our network meta-analysis; (4) only studies published in English were evaluated; (5) lack of head-to-head comparisons of some treatments; (6) different measurement methods were used in different trial, which may cause deviation; and (7) with the lack of cycles in the included trials, the inconsistency factors cannot be calculated, and node-splitting method cannot be performed in our network meta-analysis to check the inconsistency. Conclusions Compared with other drugs, lidocaine was the most effective and most tolerable drug to be recommended for PHN.

Transcriptional Response of Osmolyte Synthetic Pathways and Membrane Transporters in a Euryhaline Diatom During Long-term Acclimation to a Salinity Gradient.

How diatoms respond to fluctuations in osmotic pressure is important from both ecological and applied perspectives. It is well known that osmotic stress affects photosynthesis and can result in the accumulation of compounds desirable in pharmaceutical and alternative fuel industries. Gene expression responses to osmotic stress have been studied in short-term trials, but it is unclear whether the same mechanisms are recruited during long-term acclimation. We used RNA-seq to study the genome-wide transcription patterns in the euryhaline diatom, Cyclotella cryptica, following long-term acclimation to salinity that spanned the natural range of fresh to oceanic water. Long-term acclimated C. cryptica exhibited induced synthesis or repressed degradation of the osmolytes glycine betaine, taurine and dimethylsulfoniopropionate (DMSP). Although changes in proline concentration is one of the main responses in short-term osmotic stress, we did not detect a transcriptional change in proline biosynthetic pathways in our long-term experiment. Expression of membrane transporters showed a general tendency for increased import of potassium and export of sodium, consistent with the electrochemical gradients and dependence on co-transported molecules. Our results show substantial between-genotype differences in growth and gene expression reaction norms and suggest that the regulation of proline synthesis important in short-term osmotic stress might not be maintained in long-term acclimation. Further examination using time-course gene expression experiments, metabolomics and genetic validation of gene functions would reinforce patterns inferred from RNA-seq data.

The Long Tail Problem: Novel Parametric Methods Still Underestimate Conditional Long-Term Survival In Glioblastoma

The new potential for Long-Term Survival (LTS) in glioblastoma (GBM) demonstrated by the EF-14 trial, which showed significant survival benefit from adding Tumor-Treating Fields (TTFields) to maintenance temozolomide (TMZ) in newly diagnosed GBM (Stupp 2017), has made predictive modeling of LTS highly relevant for clinical and policy decision making. Reliable models must account for the evolution in prognosis over time in GBM. Previous studies (Bernard-Arnoux 2016, Connock 2019) have parametrically modeled the survival impact of TTFields with EF-14 data, but their results suffer from poor in-sample fit, clinical inconsistency, and poor fit to long-term epidemiological data. Here we evaluate LTS predictions from a novel, Responder Analysis-based method of parametric modeling with EF-14 data. Patients were classified as responders (R) or non-responders (NR) according to their Progression-Free Survival (PFS). If a patient’s PFS met or exceeded a given threshold time (TT), then they were classified as R. Otherwise they were classified as NR. Differences between R’s and NR’s Kaplan-Meier curves and resultant significance levels were studied for a range of TT’s. These significance levels are the result of the impact of longer PFS on OS and the opposing effect of smaller R-subgroup sample size with larger TT's. In the TTFields+TMZ arm, 10 months was the most significant TT, while in the TMZ-only arm, the most significant TT was 6.5 months. TT’s with high significance in both arms were selected for further study, including 10, 12, 18, and 20 months. Parametric survival distributions were separately calibrated for each R and NR subgroup in each trial arm using Maximum Likelihood Estimation. We studied results from exponential, Weibull, log-normal, log-logistic, Gamma, Gompertz, and Generalized Gamma and F distributions. The long-term conditional survival probabilities from each model were then calculated or estimated with Monte Carlo simulation and compared to epidemiological results from Porter et al. (2011) and from separate SEER database searches. For every TT and parametrization studied, the models for the R-subgroups clearly underestimated conditional LTS probabilities compared to epidemiological results beyond 5 years. Errors in these conditional probability estimates ranged from approximately -20% to -50% with models for TTFields+TMZ responders, while models for TMZ-only responders performed even worse, outputting values near 0% for conditional survival probabilities. This analysis provides further evidence that parametric models trained exclusively on relatively short-term EF-14 trial data, even with responder analysis-based enhancements, suffer from biases that limit their usefulness for LTS modeling in GBM. Long-term epidemiology data and modeling approaches that incorporate this data (Guzauskas 2018) are therefore necessary for informed decision making regarding novel treatments in glioblastoma.

Drug treatments for managing cystic fibrosis-related diabetes.

Drug treatments for managing cystic fibrosis-related diabetes.

Effects of Acute Exercise on Drug Craving, Self-Esteem, Mood, and Affect in Adults with Polysubstance Use Disorder: Protocol for a Multicenter Randomized Controlled Trial.

BackgroundNovel treatments for substance use disorders are needed. Acute bouts of exercise can improve mood states and craving in nonclinical populations. Exercise effects in those with polysubstance dependence are understudied; controlled trials are needed.ObjectiveThis protocol describes a clinical study examining the short-term psychological effects of 2 types of physical activity, soccer and circuit training, in patients with substance use disorders. Effects will be compared with a nonexercise control group. Specific aims are to investigate whether there are differences between the activities and the duration of changes.MethodsThis study is a short-term multicenter randomized control trial with a crossover design. Patients consecutively admitted to 4 inpatient treatment centers were invited to participate in 3 conditions, each lasting 45 minutes, within one week. The order of the conditions was randomized. There were a total of 5 assessments, taken at baseline, immediately before each condition, immediately after each condition, and 1, 2, and 4 hours postintervention, enabling patterns of change over time to be observed. Psychological effects were assessed with self-report questionnaires, which included scales for craving, state anxiety, positive and negative affect, self-esteem, and mood. Exercise intensity was assessed with the Borg Rating of Perceived Exertion scale and a heart rate monitor (Polar M200; Polar Electro Ltd). Cortisol was assessed in saliva before and 4 hours after the intervention.ResultsA total of 39 patients were included in the study. Data collection was completed in 2019.ConclusionsWe anticipate larger improvements in the intervention groups than among controls, indicating positive psychological effects during and after exercise. The study will add clinically relevant information about the short-term psychological effects of exercise in the treatment of substance use disorders, using activities that are easily accessible in different clinical settings.Trial RegistrationGerman Clinical Trials Register DRKS00018869; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00018869International Registered Report Identifier (IRRID)DERR1-10.2196/18553

No effect of resveratrol supplementation after 6 months on insulin sensitivity in overweight adults: a randomized trial

ABSTRACTBackgroundEffects of resveratrol on metabolic health have been studied in several short-term human clinical trials, with conflicting results. Next to dose, the duration of the clinical trials may explain the lack of effect in some studies, but long-term studies are still limited.ObjectivesThe objective of this study was to investigate the effects of 6-mo resveratrol supplementation on metabolic health outcome parameters.MethodsForty-one overweight men and women (BMI: 27–35 kg/m2; aged 40–70 y) completed the study. In this parallel-group, double-blind clinical trial, participants were randomized to receive either 150 mg/d of resveratrol (n = 20) or placebo (n = 21) for 6 mo. The primary outcome of the study was insulin sensitivity, using the Matsuda index. Secondary outcome measures were intrahepatic lipid (IHL) content, body composition, resting energy metabolism, blood pressure, plasma markers, physical performance, quality of life, and quality of sleep. Postintervention differences between the resveratrol and placebo arms were evaluated by ANCOVA adjusting for corresponding preintervention variables.ResultsPreintervention, no differences were observed between the 2 treatment arms. Insulin sensitivity was not affected after 6 mo of resveratrol treatment (adjusted mean Matsuda index: 5.18 ± 0.35 in the resveratrol arm compared with 5.50 ± 0.34 in the placebo arm), although there was a significant difference in postintervention glycated hemoglobin (HbA1c) between the arms (P = 0.007). The adjusted means showed that postintervention HbA1c was lower on resveratrol (35.8 ± 0.43 mmol/mol) compared with placebo (37.6 ± 0.44 mmol/mol). No postintervention differences were found in IHL, body composition, blood pressure, energy metabolism, physical performance, or quality of life and sleep between treatment arms.ConclusionsAfter 6 mo of resveratrol supplementation, insulin sensitivity was unaffected in the resveratrol arm compared with the placebo arm. Nonetheless, HbA1c was lower in overweight men and women in the resveratrol arm. This trial was registered at Clinicaltrials.gov as NCT02565979.

Design of electrical submersible pumps in methane hydrate production wells: A case study in Nankai trough methane hydrates

Gas hydrate industry aims to conduct long-term gas hydrate production trials after gaining the experiences in short-term gas hydrate production trials. Electrical submersible pumps (ESP) were mostly chosen in gas hydrate production trials to depressurize gas hydrate reservoirs. However, there is a knowledge gap about the usage and design of ESP systems in gas hydrate wells. Therefore, in this study, it is aimed to design ESP systems in methane hydrate production well in the conditions of Nankai Trough (Japan) methane hydrate reservoirs. For this purpose, a set of python codes was written to design ESP in the case study gas hydrate well and also HEP simulator was used to predict gas hydrate formation risks along the wellbore during gas production from methane hydrates via ESP production string. It was shown that high variances in water production rates (50–794 m3/day) affect the pump performance negatively, especially in the outside of suggested pump working flow rates. Moreover, pump efficiencies decrease from 70 s% to 20 s% in the outside of pump working flow rates due to huge variances in water flow rates during production. Different than conventional gas wells, the temperature rise generated by the motor is important to avoid any gas hydrate formation in gas hydrate well, which was affected by the operating frequency. Above 40 Hz of operating frequency, well temperature increases (nearly 0.65–1.75°C) by the motor with increasing frequency, which is good for the prohibition of gas hydrate formation in the well. In terms of pump power requirements, there is no difference of producing water at sea surface and releasing produced water to the seafloor. According to the methane hydrate equilibrium predictions in the wellbore during production with ESP, methane hydrate is not like to form in the design conditions. However, with ESP malfunction, methane hydrate might form inside the well due to increasing wellbore pressure and decreasing well temperature.

Acceptance of and six-month adherence to continuous positive airway pressure in patients with moderate to severe obstructive sleep apnea.

Continuous positive airway pressure (CPAP) is the most effective treatment for moderate to severe obstructive sleep apnea (OSA). Acceptance of and adherence to CPAP are crucial for optimal treatment outcomes. The aim of this study was to investigate the factors influencing patients' acceptance of and adherence to CPAP treatment. One hundred eighty-eight patients with moderate to severe OSA who had received CPAP titration from October 2017 to September 2018 were recruited. They were interviewed at 2weeks and at 6months to assess CPAP use and barriers to acceptance and adherence. One hundred fourteen patients (60.6%) accepted CPAP treatment. Disease severity, assessed by apnea-hypopnea index (AHI) (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.08), subjective satisfaction of titration (OR, 12.83; 95% CI, 3.83-42.99), initial intention of CPAP therapy (OR, 3.33; 95% CI, 1.05-10.51) and short-term home CPAP trial (OR, 9.40; 95% CI, 2.85-31.08) were associated with acceptance of CPAP treatment. Two-third of the 98 CPAP acceptors reported good CPAP adherence at 6months follow-up. Average hours of CPAP use per day for the first 2weeks (OR, 1.88; 95% CI, 1.28-3.04) and the global problems associated with CPAP use (OR, 0.82; 95% CI, 0.73-0.91) were independent predictors of the six-month CPAP adherence. Nearly 40% of patients with moderate to severe OSA did not accept CPAP treatment, and one-third of those CPAP acceptors had poor adherence to CPAP treatment. Improvement in disease awareness, comfortable titration experience, short-term home CPAP trial may be of help to increase CPAP acceptance and early experience with CPAP is important for long-term adherence. The differences in predicting factors for CPAP acceptance and adherence highlight the importance of focusing on specific aspects during the whole process management of OSA.

Comparative efficacy of placebos in short-term antidepressant trials for major depression: a secondary meta-analysis of placebo-controlled trials

BackgroundThe issue of unblinded outcome-assessors and patients has repeatedly been stressed as a flaw in allegedly double-blind antidepressant trials. Unblinding bias can for example result from a drug‘s marked side effects. If such unblinding bias is present for a given drug, then it might be expected that the placebos of that drug are rated significantly less effective than that of other antidepressants.MethodsTo test this hypothesis, the present exploratory analysis conducted a Bayesian network meta-analysis (NMA) comparing the efficacy of 19 different placebos in placebo-controlled trials provided in the dataset by Cipriani et al. (Lancet 2018; 391: 1357–66). Primary outcome was efficacy (continuous) estimated on the standardized mean difference (SMD) scale and defined as the pre-post change on the Hamilton Depression scale (HAMD-17), on which information was available in N = 258 trials.ResultsComparative placebo ranking suggested mirtazapine-placebo (SMD -2.0 [− 5.0–1.0 95% CrI]) to be the most, and amitriptyline- (SMD 1.2 [− 1.6–3.9 95% CrI]) and trazodone- (SMD 2.1 [− 0.9–5.2 95% CrI]) placebos to be the least effective placebos. Other placebos suggested to be more effective than amitriptyline- and trazodone-placebos (based on 95% CrIs excluding zero) were citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, and venlafaxine placebos. These NMA results were corroborated by the observation that the relative efficacy between drug and placebo was considerably larger for amitriptyline and trazodone than for instance mirtazapine, duloxetine, and venlafaxine, supported by a small and insignificant correlation between drug-efficacy and placebo-efficacy (r = − 0.202, p = 0.408).DiscussionThe present exploratory NMA indicates that distinguishable side effects of older drugs may unblind outcome-assessors thus resulting in overestimation of the average drug-placebo difference and underrating bias in placebo-arms, particularly for the older antidepressant drugs amitriptyline and trazodone. If confirmed in prospective studies, these findings suggest that efficacy rankings for antidepressants are susceptible to bias and should be considered unreliable or misleading. The analysis is limited by the focus on the single-comparison placebos (76%, i.e., placebos assessed in two-arm trials), since double-comparison placebos (25%, i.e., placebos assessed in three-arm trials) are hard to interpret and therefore not included in the present interpretation. Another limitation is the problem of multiplicity, which was only approximately accounted for in the Bayesian NMA by modelling treatment effects as exchangeable.

Effects of Dietary Inclusion of Seaweed, Heat Stress and Genetic Strain on Performance, Plasma Biochemical and Hematological Parameters in Laying Hens.

Simple SummaryPrebiotics such as seaweeds have been proposed as positive influencers on hen health and productivity, including their response to stressors such as heat. The present study was undertaken to evaluate the effects of 3% red seaweed Chondrus crispus and 0.5% brown seaweed Ascophyllum nodosum supplements on the heat stress responses in two genetic strains of laying hens, Lohmann LSL-Lite (White) and Lohmann Brown-Lite (Brown). The short-term seaweed diet had little effect on blood characteristics, but long-term feeding affected several blood chemistry values. The seaweed supplement reduced the feed intake and improved the feed/egg efficiency in the short term, although did not consistently affect the long-term performance. Heat stress affected the leukocyte count and some plasma chemistry parameters, particularly in the Brown layer strain. Our results showed better production, feed efficiency and resistance to heat stress in the White layer strain, with significant liver enzyme changes in alkaline phosphatase (ALP), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT). More research on the biological effects of seaweed supplementation is necessary to better understand its impacts on health and performance.This study was planned to investigate the effects of seaweed supplementation, genetic strain, heat stress and their interactions on laying hen performances, blood chemistry and hematology. In a short-term trial, laying hens of the two genetic lines Lohman LSL-Lite (White) and Lohman Brown-Lite (Brown) were supplemented with Chondrus crispus (CC) at 3% for 21 days, while a control group was not. In a long-term trial, the same two strains were assigned to control (0%), 3% red seaweed Chondrus crispus (CC) or 0.5% brown seaweed Ascophyllum nodosum (AN)-supplemented diets for 41 weeks, concluding with a four-week control or heat-stress period. The White hens displayed higher egg production and a lower feed/egg ratio. The short-term inclusion of CC significantly reduced the feed intake, weight gain and feed/egg ratio. The long-term seaweed intake affected the plasma albumin and gamma-glutamyl transferase (GGT) (p < 0.05), and there were significant strain-heat stress interactions; heat stress in the Brown birds was associated with reduced protein, globulin and glucose and increased cholesterol and GGT levels and higher heterophil-to-lymphocyte (H/L) ratios (p < 0.05) in response to heat stress (p < 0.05). In conclusion, a long-term seaweed supplementation affected the plasma protein and enzyme profiles, yet had little effect on hen leukocyte counts and the overall performance.