Non-relevant Differences Research Articles

ChatGPT-4 and Human Researchers Are Equal in Writing Scientific Introduction Sections: A Blinded, Randomized, Non-inferiority Controlled Study.

Background Natural language processing models are increasingly used in scientific research, and their ability to perform various tasks in the research process is rapidly advancing. This study aims to investigate whether Generative Pre-trained Transformer 4 (GPT-4) is equal to humans in writing introduction sections for scientific articles. Methods This randomized non-inferiority study was reported according to the Consolidated Standards of Reporting Trials for non-inferiority trials and artificial intelligence (AI) guidelines. GPT-4 was instructed to synthesize 18 introduction sections based on the aim of previously published studies, and these sections were compared to the human-written introductions already published in a medical journal. Eight blinded assessors randomly evaluated the introduction sections using 1-10 Likert scales. Results There was no significant difference between GPT-4 and human introductions regarding publishability and content quality. GPT-4 had one point significantly better scores in readability, which was considered a non-relevant difference. The majority of assessors (59%) preferred GPT-4, while 33% preferred human-written introductions. Based on Lix and Flesch-Kincaid scores, GPT-4 introductions were 10 and two points higher, respectively, indicating that the sentences were longer and had longer words. Conclusion GPT-4 was found to be equal to humans in writing introductions regarding publishability, readability, and content quality. The majority of assessors preferred GPT-4 introductions and less than half could determine which were written by GPT-4 or humans. These findings suggest that GPT-4 can be a useful tool for writing introduction sections, and further studies should evaluate its ability to write other parts of scientific articles.

Effect of intra-operative intravenous lidocaine on opioid consumption after bariatric surgery: a prospective, randomised, blinded, placebo-controlled study.

Peri-operative lidocaine infusion warrants investigation in bariatric surgery because obese patients present different physiological and pharmacological risks. This single-centre, prospective, randomised double-blind placebo-controlled study enrolled obese patients scheduled for laparoscopic bariatric surgery using an enhanced recovery protocol. Patients received either lidocaine (bolus of 1.5mg.kg-1 , then a continuous infusion of 2mg.kg-1 .h-1 until the end of the surgery, then 1mg.kg-1 .h-1 for 1h in the recovery area) or identical volumes and rates of 0.9% saline. The primary outcome was the consumption of the equivalent of oxycodone consumption over the first 3 postoperative days. Secondary outcomes were: postoperative pain; incidence of nausea and vomiting; bowel function recovery; and lengths of stay in the recovery area and in hospital. Plasma concentrations of lidocaine were measured. On the 178 patients recruited, data were analysed from 176. The median (IQR [range]) equivalent intravenous oxycodone consumption was 3.3mg (0.0-6.0 [0.0-14.5]) and 5.0mg (3.3-7.0 [3.3-20.0]) in the lidocaine and saline groups, respectively (difference between medians (95%CI): 1.7 (0.6-3.4) mg; p=0.004). Length of stay in the recovery area, postoperative pain, nausea and vomiting, day of recovery of bowel function, and length of stay in hospital were not different between groups. Mean (SD) lidocaine plasma concentrations were 2.44 (0.70) µg.ml-1 and 1.77 (0.51) µg.ml-1 at the end of surgery and 1 hour after the end of infusion, respectively. Lidocaine infusion during bariatric surgery resulted in a clinically non-relevant difference in postoperative oxycodone consumption.

Comparative selective retention of particle size classes in the gastrointestinal tract of ponies and goats.

There is a discrepancy in the literature on potential digesta separation mechanisms in horses, with both a selective retention of fine and of large particles postulated in different publications. To assess the net effect of such mechanisms, we fed ponies on a hay-only diet a pulse dose of whole (unchopped) marked hay together with a solute marker, collected faeces on a regular basis, measured marker concentrations in whole faeces and in their large (2.0-16mm), medium (0.5-1.0mm) and small (0.063-0.25mm) particle fraction, and calculated the corresponding mean retention times (MRTs). For comparison, the same experiment was performed in goats. In goats, as expected, MRTsolute (35hr) was significantly shorter than MRTparticle (51hr); only a very small fraction of particle marker was excreted as large particles (2%); and the MRT of these large particles was significantly shorter than that of small particles (with a relevant difference of 8.6hr), indicating that those few large particles that escape the rumen do so mostly soon after ingestion. In ponies, MRTsolute (24hr) did not differ from MRTparticle (24hr); a higher fraction of particle marker was excreted as large particles (5%); and the MRT of these large particles was longer than that of small particles (but with a non-relevant difference of less than 1hr). These results indicate that no relevant net separation of digesta phases occurs in horses and that selective particle retention mechanisms in the large intestine are unlikely to represent important characteristics of the horse's digestive physiology.

Content Validity of a Short Calcium Intake List to Estimate Daily Dietary Calcium Intake of Patients with Osteoporosis

PurposeCalcium supplements are prescribed for prevention of osteoporotic fractures, but there is controversy whether excess of calcium intake is associated with cardiovascular events. While an accurate estimation of dietary calcium intake is a prerequisite to prescribe the adequate amount of supplementation, the most adequate tools for estimating intake are time-consuming. The aim of this study is to validate a short calcium intake list (SCaIL) that is feasible in daily clinical practice.MethodsBased on the food groups contributing most to daily dietary calcium intake and portion sizes determined in an earlier study, a three-item, 1-min SCaIL was designed. As a reference method, an extensive dietary history (DH) with specific focus on calcium-rich foods and extra attention for portion sizes was performed. Beforehand, a difference of ≥250 mg calcium between both methods was considered clinically relevant.ResultsSixty-six patients with either primary (n = 40) or secondary (n = 26) osteoporosis were included. On average, the SCaIL showed a small and clinically non-relevant difference in calcium intake with the DH: 24 ± 350 mg/day (1146 ± 440 vs. 1170 ± 485 mg, respectively; p = 0.568). Sensitivity and specificity of the SCaIL, compared to the DH, were 73 and 80%, respectively. However, in 50% of the individuals, a clinically relevant difference of ≥250 mg calcium was observed between both methods, while in 17% this was even ≥500 mg.ConclusionsThe SCaIL is a quick and easy questionnaire to estimate dietary calcium intake at a group level, but is not sufficiently reliable for use in individual patients. Remarkably, the mean dietary calcium intake estimated by the DH of 1170 mg/day indicates that a large proportion of osteoporosis patients might not even need calcium supplementation, although more data are needed to confirm this finding.

Equivalence Testing With Particle Size Distribution Data: Methods and Applications in the Development of Inhalative Drugs

ABSTRACTKey criteria of the quality of inhalative drugs are assessed in experiments generating so-called particle size distributions as data. Many experiments of that kind are carried out to demonstrate that necessary modifications to whatever part of the manufacturing process do not substantially change basic characteristics of an inhalable drug product. The equivalence testing procedures we derive for that purpose rely on different models accommodating the specific structure of such data and on different ways of specifying the region of nonrelevant differences. For each hypotheses formulation, three different tests are derived (two parametric and one asymptotically distribution-free procedures) and compared in terms of level and power. The results support the conclusion that the asymptotically distribution-free procedure exhibits surprisingly favorable properties. Supplementary materials for this article are available online.

Equivalent bronchodilation with budesonide/formoterol combination via Easyhaler and Turbuhaler in patients with asthma

BackgroundTherapeutic equivalence of Budesonide/formoterol Easyhaler compared to Symbicort Turbuhaler has been previously demonstrated with in vitro and pharmacokinetic studies. This study was performed to confirm equivalent bronchodilator efficacy of the products in asthmatic patients. MethodsA randomised, single-dose, 4-period crossover study was carried out in a double-blind, double-dummy manner in 11 study sites. The studied doses were 320/9 μg and 1280/36 μg of budesonide/formoterol delivered by Easyhaler and Turbuhaler. Spirometry was performed before and 10 min, 20 min and 1, 2, 3, 4, 6, 8, 10 and 12 h after administration of the study treatments. The primary efficacy endpoint was average 12-h forced expiratory volume in 1 s (FEV1). The secondary efficacy endpoints were maximum FEV1 and FEV1 at 12 h post-dose. Results72 asthma patients with reversible airway obstruction were randomised to receive study treatments. 53 patients completed all study periods according to the protocol and had sufficient data available to calculate the primary endpoint. They were included in the per-protocol analyses. The assay sensitivity of the study was shown as the common slope of average 12-h FEV1 between doses was 0.063 (95% CI 0.032–0.093) and showed statistical significance (p < 0.001). In equivalence testing, the difference in average 12-h FEV1 between the treatments (Easyhaler-Turbuhaler) was 0.013 l at the lower dose and −0.028 l at the higher dose, and their 95% confidence intervals (CIs) (−0.047 to 0.073 and −0.087 to 0.032, respectively) fell within the range of a clinically non-relevant difference. The results of the secondary efficacy endpoints were in line with the results of the primary endpoint. All treatments were well tolerated. ConclusionsThe results confirm equivalent bronchodilator efficacy of Budesonide/formoterol Easyhaler compared to Symbicort Turbuhaler. Trial registrationThis trial was registered on ClinicalTrials.gov, Identifier: NCT02308098.

The Festuco-Brometea Grasslands on Sandstone and Marl-Clay-Sandstone Substrata in Tuscany (Northern-Central Italy)

Abstract The grasslands dominated by Bromus erectus and/or Brachypodium rupestre cover large areas on sandstone and marl-clay-sandstone substrata (limestone is excluded), of the Apennines and pre-Apennines between Pistoia and Arezzo provinces (Tuscany, Central Italy). Our investigation was focused on to 71 unpublished releves and 45 literature releves from Tuscany and surrounding areas, reporting the original releves of Astragalo monspessulani-Brometum erecti, Centaureo bracteatae-Brometum erecti and Ononido masquillerii-Brometum erecti. The releves were submitted to exploratory multivariate analysis, allowing to detect nine distinct groups. Their consistence was verified by mean of NMDS against Ellenberg/Pignatti indicator values, and CCA constrained against chorotypes and growth forms. Diagnostic species of the definitive groups resulting from the analysis were chosen according to species fidelity, based on the φ coefficient of association. The analysis splits the data set in two main subclusters; the first one (A) includes few releves of low altitude, thermophilous conenoses, interpreted as a transition between the submediterranean aspects of Festuco-Brometea class and other Mediterranean herbaceous and shrubby classes; the second subcluster (B) includes most of the data set and can be clearly subdivided in pioneering, mesoxerophilous communities (B1 and B2a groups) and mesophilous communities (B2b group). The releves of clusters B1 and B2a are referred to Coronillo minimae-Astragaletum monspessulanii association and to three other groups: Plantago argentea-Carex caryophyllea communities, Tragopogon samaritani-Bromus erectus communities, Festuco trachyphyllae-Brometum erecti ass. nova. The mesophilous group (B2b) includes the original Centaureo bracteatae-Brometum erecti and Ononido masquillerii-Brometum erecti releves, together with a slightly differentiated community; due to the non-relevant differences between these grassland types from floristic, ecological and chorological perspectives, we propose herewith to treat them as three subassociations of Centaureo bracteatae-Brometum erecti (typicum, ononidetosum masquillerii and linetosum cathartici). Post-cultural grasslands in human-disturbed areas were also detected. All these communities can be attributed to Polygalo mediterraneae-Bromenion erecti suballiance (Bromion alliance), even if a clear subdivision between the mesoxerophilous pioneer aspects and the more mesophilous and evolved ones can be noted.

Comparison of Two Formulations of Sodium Divalproate Plasma Concentrations after a Single 500 mg Oral Dose in Healthy Subjects, and Stochastic Sub-analysis of the Individual ?Clinical Perceptible? Levels

A new generic formula containing 500 mg of sodium divalproate in enteric releasing coated tablets was compared to the reference product in a pharmacokinetic, randomized, cross-over 2×2 study performed in 24 healthy adult males. After administering a single dose, it was demonstrated that the maximum plasma concentration of valproic acid varies within the 98.4-113.0 range for 90% CI (test/reference); and the area under the curve of plasma levels over the 24 h period following the intake varies within the 91.1-99.5 range; therefore, it can be seen that both parameters are within the range of acceptance for the interchangeability of the products. Individual results show the typical inter- subject and inter -treatment variations of divalproate. Since the latter have an impact on the prescription decision, results are sub-analyzed considering a plasma threshold of valproic acid as effective or stochastically clinical perceptible (Cper).Complete duration of plasma levels above Cper is comparable for both formulations (p<0.81); nevertheless, the test product reaches the Cper value faster than the reference compound (p<0.04). Therefore, we consider that the individual perception of efficacy of the generic product should not be inferior to that of the reference. In conclusion, the tested formula is bioequivalent and the further sub-analysis of individual variations above a plasma level of stochastic clinical perception of effects shows non-relevant differences between both brands.

F661 STAYING AT WORK WITH CHRONIC MUSCULOSKELETAL PAIN: A NEW REFERENCE FOR PAIN REHABILITATION

European Journal of Pain SupplementsVolume 5, Issue S1 p. 186-187 F661 STAYING AT WORK WITH CHRONIC MUSCULOSKELETAL PAIN: A NEW REFERENCE FOR PAIN REHABILITATION H.J. de Vries, H.J. de Vries Department of Rehabilitation MedicineSearch for more papers by this authorS. Brouwer, S. Brouwer Department of Health Sciences, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsSearch for more papers by this authorJ.W. Groothoff, J.W. Groothoff Department of Health Sciences, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsSearch for more papers by this authorJ.H.B. Geertzen, J.H.B. Geertzen Department of Rehabilitation MedicineSearch for more papers by this authorM.F. Reneman, M.F. Reneman Department of Rehabilitation MedicineSearch for more papers by this author H.J. de Vries, H.J. de Vries Department of Rehabilitation MedicineSearch for more papers by this authorS. Brouwer, S. Brouwer Department of Health Sciences, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsSearch for more papers by this authorJ.W. Groothoff, J.W. Groothoff Department of Health Sciences, University Medical Center Groningen, University of Groningen, Groningen, The NetherlandsSearch for more papers by this authorJ.H.B. Geertzen, J.H.B. Geertzen Department of Rehabilitation MedicineSearch for more papers by this authorM.F. Reneman, M.F. Reneman Department of Rehabilitation MedicineSearch for more papers by this author First published: 30 January 2012 https://doi.org/10.1016/S1754-3207(11)70641-1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume5, IssueS1September 2011Pages 186-187 RelatedInformation

Population Pharmacokinetics of??Levetiracetam in Japanese and??Western Adults

To assess the population pharmacokinetics of levetiracetam, a second-generation antiepileptic drug, in adult Japanese and Western populations. Data were pooled from ten matched clinical trials conducted in Japan and in Europe and the USA, in which levetiracetam was administered orally to healthy subjects and subjects with epilepsy. Overall, 5408 plasma concentrations were available from 524 subjects in six clinical pharmacology studies and two confirmatory and two long-term safety studies of add-on treatment for partial epilepsy. A one-compartment open model with first-order absorption and elimination was fitted to the plasma concentrations using nonlinear mixed-effects modelling with first-order estimation. Ethnicity had no statistically significant effect on the pharmacokinetics of levetiracetam in the presence of the other covariates. Bodyweight, sex, creatinine clearance and concomitant intake of enzyme inducers or valproic acid had a statistically significant effect on apparent plasma clearance of levetiracetam. Bodyweight, disease and valproic acid had a statistically significant effect on the volume of distribution. Levetiracetam exposure (the area under the plasma concentration-time curve over the 12-hour dosing interval at steady state) was 12% higher in females than in males. Decreasing bodyweight from 70 kg to 40 kg was predicted to increase exposure by 16%, while halving creatinine clearance was predicted to increase exposure by 10%. Enzyme inducers reduced exposure by 8%, while valproic acid resulted in a 23% increase in exposure. The latter effect was assumed to arise from the known association between valproic acid and increased body fat, since levetiracetam is negligibly metabolised by cytochrome P450 enzymes. Population pharmacokinetic analysis points to the absence of ethnic differences in the pharmacokinetics of levetiracetam between Japanese and Western populations, other than those arising from bodyweight differences. Small, clinically non-relevant differences between individual demographic characteristics suggest that dose adjustment is usually not necessary.

The Rule of Law and Legal Efficacy: Private Values Versus General Standards

LTHOUGH citizens do not always comply with laws they approve, a primary factor which affects the ability of a law to produce deliberate social change Xis the degree of public support for it.1 A growing literature examines and speculates on a wide range of variables which shape individual attitudes toward certain laws, and thus influence the degree of compliance,2 e.g., perceptions of the legitimacy of the law, compatibility of the law with cultural or regional norms, and attitudes toward the source of the law. The same literature examines a number of variables which might influence an individual to obey a law despite his partial or serious disagreement with it (e.g., sanctions or partiotism). While prior research rightly focuses on the role of individual attitudes as determinants of compliance, in this paper we examine a largely ignored but potentially important factor in the compliance equation -public commitment to rule of law. In Western societies particularly, there is a tendency to assume public acceptance of socially prescribed rules which members of society not only obey, but accept as general standards that should be applied equitably to all members of society. A general standard stipulates how a law is to be applied prior to and independent of the consequences of a specific application. A general standard implies that unless there are relevant differences between individuals (e.g., adults vs. minors), a law is to be applied uniformly. Non-relevant differences, such as race, however, would not be a justifiable basis for variable applications of a law.3