Effects of the selective AMPA modulator NBI-1065845 on the pharmacokinetics of midazolam or ethinyl estradiol-levonorgestrel in healthy adults.

This parallel-arm, phase I study investigated the potential cytochrome P450 (CYP)3A induction effect of NBI-1065845 (TAK-653), an investigational α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor potentiator in phase II development for major depressive disorder. The midazolam treatment arm received the sensitive CYP3A substrate midazolam on Day 1, followed by NBI-1065845 alone on Days 5-13; on Day 14, NBI-1065845 was administered with midazolam, then NBI-1065845 alone on Day 15. The oral contraceptive treatment arm received ethinyl estradiol-levonorgestrel on Day 1, then NBI-1065845 alone on Days 5-13; on Day 14, NBI-1065845 was administered with ethinyl estradiol-levonorgestrel, then NBI-1065845 alone on Days 15-17. Blood samples were collected for pharmacokinetic analyses. The midazolam treatment arm comprised 14 men and 4 women, of whom 16 completed the study. Sixteen of the 17 healthy women completed the oral contraceptive treatment arm. After multiple daily doses of NBI-1065845, the geometric mean ratios (GMRs) (90% confidence interval) for maximum observed concentration were: midazolam, 0.94 (0.79-1.13); ethinyl estradiol, 1.00 (0.87-1.15); and levonorgestrel, 0.99 (0.87-1.13). For area under the plasma concentration-time curve (AUC) from time 0 to infinity, the GMRs were as follows: midazolam, 0.88 (0.78-0.98); and ethinyl estradiol, 1.01 (0.88-1.15). For levonorgestrel, the GMR for AUC from time 0 to the last quantifiable concentration was 0.87 (0.78-0.96). These findings indicate that NBI-1065845 is not a CYP3A inducer and support its administration with CYP3A substrates. NBI-1065845 was generally well tolerated, with no new safety signals observed after coadministration of midazolam, ethinyl estradiol, or levonorgestrel.

Pharmacokinetic interactions between fexuprazan, a potassium-competitive acid blocker, and nonsteroidal anti-inflammatory drugs in healthy males.

Fexuprazan, a novel potassium-competitive acid blocker, is expected to be used for the prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) induced ulcer. This study aimed to evaluate pharmacokinetic (PK) interactions between fexuprazan and NSAIDs in healthy subjects. A randomized, open-label, multicenter, six-sequence, one-way crossover study was conducted in healthy male subjects. Subjects randomly received one of the study drugs (fexuprazan 40 mg BID, celecoxib 200 mg BID, naproxen 500 mg BID, or meloxicam 15 mg QD) for 5 or 7 days in the first period followed by the combination of fexuprazan and one of NSAIDs for the same days and the perpetrator additionally administered for 1-2 days in the second period. Serial blood samples for PK analysis were collected until 48- or 72-h post-dose at steady state. PK parameters including maximum plasma concentration at steady state (Cmax,ss) and area under plasma concentration-time curve over dosing interval at steady state (AUCτ,ss) were compared between monotherapy and combination therapy. The PKs of NSAIDs were not significantly altered by fexuprazan. For fexuprazan, differences in PK parameters (22% in Cmax, 19% in AUCτ,ss) were observed when co-administered with naproxen, but not clinically significant. The geometric mean ratio (90% confidence interval) of combination therapy to monotherapy for Cmax,ss and AUCτ,ss was 1.22 (1.02-1.46) and 1.19 (1.00-1.43), respectively. There were no significant changes in the systemic exposure of fexuprazan by celecoxib and meloxicam. Fexuprazan and NSAIDs did not show clinically meaningful PK interactions.

St. John's wort extract with a high hyperforin content does not induce P-glycoprotein activity at the human blood-brain barrier.

St. John's wort (SJW) extract, a herbal medicine with antidepressant effects, is a potent inducer of intestinal and/or hepatic cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp), which can cause clinically relevant drug interactions. It is currently not known whether SJW can also induce P-gp activity at the human blood-brain barrier (BBB), which may potentially lead to decreased brain exposure and efficacy of certain central nervous system (CNS)-targeted P-gp substrate drugs. In this study, we used a combination of positron emission tomography (PET) imaging and cocktail phenotyping to gain a comprehensive picture on the effect of SJW on central and peripheral P-gp and CYP activities. Before and after treatment of healthy volunteers (n = 10) with SJW extract with a high hyperforin content (3-6%) for 12-19 days (1800 mg/day), the activity of P-gp at the BBB was assessed by means of PET imaging with the P-gp substrate [11C]metoclopramide and the activity of peripheral P-gp and CYPs was assessed by administering a low-dose phenotyping cocktail (caffeine, omeprazole, dextromethorphan, and midazolam or fexofenadine). SJW significantly increased peripheral P-gp, CYP3A, and CYP2C19 activity. Conversely, no significant changes in the peripheral metabolism, brain distribution, and P-gp-mediated efflux of [11C]metoclopramide across the BBB were observed following the treatment with SJW extract. Our data suggest that SJW does not lead to significant P-gp induction at the human BBB despite its ability to induce peripheral P-gp and CYPs. Simultaneous intake of SJW with CNS-targeted P-gp substrate drugs is not expected to lead to P-gp-mediated drug interactions at the BBB.

Comparison of the forearm rotation restriction capacities of four upper-extremity immobilization methods: there is no difference between single and double sugar tong splinting.

BACKGROUND: The aim of this study was to compare the effects of four different immobilization methods [single sugar tong splint (SSTS), double sugar tong splint (DSTS), short arm cast (SAC), and long arm cast (LAC)] commonly used for restricting forearm rotation in the upper extremity. METHODS: Forty healthy volunteers were included in the study. Dominant extremities were used for measurements. Basal pronation and supination of the forearm were measured with a custom-made goniometer, and the total rotation arc was calculated without any immobilization. Next, the measurements were repeated with the SAC, LAC, SSTS and DSTS. Each measurement was compared to the baseline value, and the percentage of rotation restriction was calculated. RESULTS: The most superior restriction rates were observed for the LAC (p = 0.00). No statistically significant difference was detected between the SSTS and DSTS in terms of the restriction of supination, pronation or the rotation arc (p values, 1.00, 0.18, and 0.50, respectively). Statistically significant differences were not detected between the SAC and the SSTS in any of the three parameters (p values, 0.25; 1.00; 1.00, respectively). When the SAC and DSTS were compared, while there was no significant difference between the two methods in pronation (p = 0.50), a statistically significant difference was detected in supination (p = 0.01) and in the total rotation arc (p = 0.03). CONCLUSION: The LAC provides superior results in restricting forearm rotation. The SAC and SSTS had similar effects on forearm rotation. The DSTS, which contains, in addition to the SSTS, a sugar tong portion above the elbow, does not provide additional rotational stability.

Neurovascular Coupling Analysis Based on Multivariate Variational Gaussian Process Convergent Cross-Mapping.

Neurovascular coupling (NVC) provides important insights into the intricate activity of brain functioning and may aid in the early diagnosis of brain diseases. Emerging evidences have shown that NVC could be assessed by the coupling between electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS). However, this endeavor presents significant challenges due to the absence of standardized methodologies and reliable techniques for coupling analysis of these two modalities. In this study, we introduced a novel method, i.e., the collaborative multi-output variational Gaussian process convergent cross-mapping (CMVGP-CCM) approach to advance coupling analysis of EEG and fNIRS. To validate the robustness and reliability of the CMVGP-CCM method, we conducted extensive experiments using chaotic time series models with varying noise levels, sequence lengths, and causal driving strengths. In addition, we employed the CMVGP-CCM method to explore the NVC between EEG and fNIRS signals collected from 26 healthy participants using a working memory (WM) task. Results revealed a significant causal effect of EEG signals, particularly the delta, theta, and alpha frequency bands, on the fNIRS signals during WM. This influence was notably observed in the frontal lobe, and its strength exhibited a decline as cognitive demands increased. This study illuminates the complex connections between brain electrical activity and cerebral blood flow, offering new insights into the underlying NVC mechanisms of WM.

Extending Subcortical EEG Responses to Continuous Speech to the Sound-Field.

The auditory brainstem response (ABR) is a valuable clinical tool for objective hearing assessment, which is conventionally detected by averaging neural responses to thousands of short stimuli. Progressing beyond these unnatural stimuli, brainstem responses to continuous speech presented via earphones have been recently detected using linear temporal response functions (TRFs). Here, we extend earlier studies by measuring subcortical responses to continuous speech presented in the sound-field, and assess the amount of data needed to estimate brainstem TRFs. Electroencephalography (EEG) was recorded from 24 normal hearing participants while they listened to clicks and stories presented via earphones and loudspeakers. Subcortical TRFs were computed after accounting for non-linear processing in the auditory periphery by either stimulus rectification or an auditory nerve model. Our results demonstrated that subcortical responses to continuous speech could be reliably measured in the sound-field. TRFs estimated using auditory nerve models outperformed simple rectification, and 16 minutes of data was sufficient for the TRFs of all participants to show clear wave V peaks for both earphones and sound-field stimuli. Subcortical TRFs to continuous speech were highly consistent in both earphone and sound-field conditions, and with click ABRs. However, sound-field TRFs required slightly more data (16 minutes) to achieve clear wave V peaks compared to earphone TRFs (12 minutes), possibly due to effects of room acoustics. By investigating subcortical responses to sound-field speech stimuli, this study lays the groundwork for bringing objective hearing assessment closer to real-life conditions, which may lead to improved hearing evaluations and smart hearing technologies.

Spatio-temporal dynamics of the human small intestinal microbiome and its response to a synbiotic.

Although fecal microbiota composition is considered to preserve relevant and representative information for distal colonic content, it is evident that it does not represent microbial communities inhabiting the small intestine. Nevertheless, studies investigating the human small intestinal microbiome and its response to dietary intervention are still scarce. The current study investigated the spatio-temporal dynamics of the small intestinal microbiome within a day and over 20 days, as well as its responses to a 14-day synbiotic or placebo control supplementation in 20 healthy subjects. Microbial composition and metabolome of luminal content of duodenum, jejunum, proximal ileum and feces differed significantly from each other. Additionally, differences in microbiota composition along the small intestine were most pronounced in the morning after overnight fasting, whereas differences in composition were not always measurable around noon or in the afternoon. Although overall small intestinal microbiota composition did not change significantly within 1 day and during 20 days, remarkable, individual-specific temporal dynamics were observed in individual subjects. In response to the synbiotic supplementation, only the microbial diversity in jejunum changed significantly. Increased metabolic activity of probiotic strains during intestinal passage, as assessed by metatranscriptome analysis, was not observed. Nevertheless, synbiotic supplementation led to a short-term spike in the relative abundance of genera included in the product in the small intestine approximately 2 hours post-ingestion. Collectively, small intestinal microbiota are highly dynamic. Ingested probiotic bacteria could lead to a transient spike in the relative abundance of corresponding genera and ASVs, suggesting their passage through the entire gastrointestinal tract. This study was registered to http://www.clinicaltrials.gov, NCT02018900.

Effect of systemic vascular resistance on the agreement between stroke volume by non-invasive pulse wave analysis and Doppler ultrasound in healthy volunteers.

BACKGROUND: Stroke volume can be estimated beat-to-beat and non-invasively by pulse wave analysis (PWA). However, its reliability has been questioned during marked alterations in systemic vascular resistance (SVR). We studied the effect of SVR on the agreement between stroke volume by PWA and Doppler ultrasound during reductions in stroke volume in healthy volunteers. METHODS: In a previous study we simultaneously measured stroke volume by PWA (SVPWA) and suprasternal Doppler ultrasound (SVUS). We exposed 16 healthy volunteers to lower body negative pressure (LBNP) to reduce stroke volume in combination with isometric hand grip to elevate SVR. LBNP was increased by 20 mmHg every 6 minutes from 0 to 80 mmHg, or until hemodynamic decompensation. The agreement between SVPWA and SVUS was examined using Bland-Altman analysis with mixed regression. Within-subject limits of agreement (LOA) was calculated from the residual standard deviation. SVRUS was calculated from SVUS. We allowed for a sloped bias line by introducing the mean of the methods and SVRUS as explanatory variables to examine whether the agreement was dependent on the magnitude of stroke volume and SVRUS. RESULTS: Bias ± limits of agreement (LOA) was 27.0 ± 30.1 mL. The within-subject LOA was ±11.1 mL. The within-subject percentage error was 14.6%. The difference between methods decreased with higher means of the methods (-0.15 mL/mL, confidence interval (CI): -0.19 to -0.11, P<0.001). The difference between methods increased with higher SVRUS (0.60 mL/mmHg × min × L-1, 95% CI: 0.48 to 0.72, P<0.001). CONCLUSION: PWA overestimated stroke volume compared to Doppler ultrasound during reductions in stroke volume and elevated SVR in healthy volunteers. The agreement between SVPWA and SVUS decreased during increases in SVR. This is relevant in settings where a high level of reliability is required.

Stronger safeguards sought for trial 'guinea pigs'.

Global charter aims to prevent exploitation of paid, healthy volunteers in drug studies.

Determinants of hand pulse wave velocity and hand pulse transit time in healthy adults.

Arterial pulse wave velocity (PWV) is recognized as a convenient method to assess peripheral vascular stiffness. This study explored the clinical characteristics of hand PWV (hPWV) and hand pulse transit time (hPTT) in healthy adults (sixty males = 42.4 ± 13.9 yrs; sixty-four females = 42.8 ± 13.9 yrs) voluntarily participated in this study. The arterial pulse waveform and the anatomical distance from the radial styloid process to the tip of the middle finger of both hands were recorded in the sitting position. The hPWV was calculated as the traversed distance divided by hPTT between those two points. Male subjects showed significantly greater hPWV, systolic blood pressure, and pulse pressure than age-matched female subjects, while the hPTT was not significantly different between genders. Multiple linear regression analysis showed that gender is a common determinant of hPWV and hPTT, and that age and heart rate (HR) were negatively correlated with hPWV and hPTT, respectively. We conclude that male subjects have greater hPWV than female subjects. Ageing is associated with decreased hPWV, while increased HR is associated with a smaller hPTT. The hPWV and hPTT might be used as non-invasive indices to characterise the ageing and arterial stiffness of peripheral blood vessels.

The effects of music combined to paired associative stimulation on motor-evoked potentials and alertness in spinal cord injury patients and healthy subjects.

Paired associative stimulation (PAS) consisting of high-intensity transcranial magnetic stimulation (TMS) and high-frequency peripheral nerve stimulation (known as high-PAS) induces plastic changes and improves motor performance in patients with incomplete spinal cord injury (SCI). Listening to music during PAS may potentially improve mood and arousal and facilitate PAS-induced neuroplasticity via auditory-motor coupling, but the effects have not been explored. This pilot study aimed to determine if the effect of high-PAS on motor-evoked potentials (MEPs) and subjective alertness can be augmented with music. Ten healthy subjects and nine SCI patients received three high-PAS sessions in randomized order (PAS only, PAS with music synchronized to TMS, PAS with self-selected music). MEPs were measured before (PRE), after (POST), 30 min (POST30), and 60 min (POST60) after stimulation. Alertness was evaluated with a questionnaire. In healthy subjects, MEPs increased at POST in all sessions and remained higher at POST60 in PAS with synchronized music compared with the other sessions. There was no difference in alertness. In SCI patients, MEPs increased at POST and POST30 in PAS only but not in other sessions, whereas alertness was higher in PAS with self-selected music. More research is needed to determine the potential clinical effects of using music during high-PAS.

Comparative analysis of pulmonary ventilation distribution between low-cost and branded incentive spirometers using electrical impedance tomography in healthy adults: Study protocol.

BACKGROUND: The Incentive Spirometer (IS) increases lung volume and improves gas exchange by visually stimulating patients to take slow, deep breaths. It prevents respiratory complications and treats postoperative atelectasis in patients undergoing abdominal, thoracic, and neurosurgical procedures. Its effectiveness has been validated in studies that support improved lung capacities and volumes in individuals with respiratory complications, postoperative thoracic surgery, upper abdominal surgery, and bariatric surgery. The modified Pachón incentive spirometer (MPIS) is a cost-effective alternative to branded IS. It is crucial to validate whether the MPIS distributes ventilation as effectively as commercial devices do. Ventilation distribution will be measured using electrical impedance tomography. OBJECTIVE: The aim is to compare the distribution of pulmonary ventilation between the MPIS and another commercial IS in healthy adults using electrical impedance tomography. METHODS: A crossover clinical trial is proposed to evaluate the measurement of pulmonary ventilation distribution using EIT in a sample of healthy adults. All participants will use a commercial flow IS and the MPIS, with the order of assignment randomized. This research will use electrical impedance tomography to validate the operation of the MPIS. CONCLUSIONS: This study protocol will compare two incentive spirometers' impact on pulmonary ventilation, potentially endorsing the adoption of a cost-effective device to enhance accessibility for targeted populations. TRIAL REGISTRATION: The study was registered in ClinicalTrials.gov (NTC05532748).

Effect of lozenge surface texture, taste and acidity on salivary flow rate: A crossover preclinical trial in healthy subjects.

Dry mouth is a multifaceted condition which is caused by reduced salivary secretion. This study aimed to evaluate and compare the effects of different lozenge surface textures, tastes and acidity levels on stimulated salivary secretion for increased oral moistening in participants without hyposalivation. This randomized, double-blind, clinical crossover trial with before and after comparison involved 33 healthy volunteers. Five lozenges, including a baseline control (C), apple (A), sour (S), sour apple (SA) and granular pectin (P) were tested on five different days with all the subjects. Salivary flow, pH value, and subjective feeling (visual analog scale) were measured before and after consuming the lozenge each day. Throughout all trial days the unstimulated whole salivary flow (UWSF) averaged 0.65 ± 0.26 ml/min. Lozenges S, SA, and P showed higher stimulated whole salivary flow (SWSF) than C (P < 0.001) by more than 0.5 ml/min. Lozenge P, with a rough surface, demonstrated the highest difference between UWSF and SWSF, 2.41 ± 0.69 ml/min. The stimulated saliva with the lozenges containing acidifiers (S, SA and P) was more than 1.4 pH units lower compared to lozenges C and A (P < 0.001). Subjects reported the strongest subjective feeling of increased saliva with lozenges SA and P. Overall lozenges SA and P provided the best objective results in enhancing salivary flow rate and subjective feeling of increased salivary flow.

Serum Levels of Adiponectin Are Strongly Associated with Lipoprotein Subclasses in Healthy Volunteers but Not in Patients with Metabolic Syndrome.

Metabolic syndrome (MS) is a widespread disease in developed countries, accompanied, among others, by decreased adiponectin serum levels and perturbed lipoprotein metabolism. The associations between the serum levels of adiponectin and lipoproteins have been extensively studied in the past under healthy conditions, yet it remains unexplored whether the observed associations also exist in patients with MS. Therefore, in the present study, we analyzed the serum levels of lipoprotein subclasses using nuclear magnetic resonance spectroscopy and examined their associations with the serum levels of adiponectin in patients with MS in comparison with healthy volunteers (HVs). In the HVs, the serum levels of adiponectin were significantly negatively correlated with the serum levels of large buoyant-, very-low-density lipoprotein, and intermediate-density lipoprotein, as well as small dense low-density lipoprotein (LDL) and significantly positively correlated with large buoyant high-density lipoprotein (HDL). In patients with MS, however, adiponectin was only significantly correlated with the serum levels of phospholipids in total HDL and large buoyant LDL. As revealed through logistic regression and orthogonal partial least-squares discriminant analyses, high adiponectin serum levels were associated with low levels of small dense LDL and high levels of large buoyant HDL in the HVs as well as high levels of large buoyant LDL and total HDL in patients with MS. We conclude that the presence of MS weakens or abolishes the strong associations between adiponectin and the lipoprotein parameters observed in HVs and disturbs the complex interplay between adiponectin and lipoprotein metabolism.

Synbiotic Bacillus megaterium DSM 32963 and n-3 PUFA Salt Composition Elevates Pro-Resolving Lipid Mediator Levels in Healthy Subjects: A Randomized Controlled Study.

Beneficial health effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) are partly attributed to specialized pro-resolving mediators (SPMs), which promote inflammation resolution. Strategies to improve n-3 PUFA conversion to SPMs may, therefore, be useful to treat or prevent chronic inflammatory disorders. Here, we explored a synbiotic strategy to increase circulating SPM precursor levels. Healthy participants (n = 72) received either SynΩ3 (250 mg eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) lysine salts; two billion CFU Bacillus megaterium; n = 23), placebo (n = 24), or fish oil (300 mg EPA plus DHA; N = 25) capsules daily for 28 days in a randomized, double-blind placebo-controlled parallel 3-group design. Biomarkers were assessed at baseline and after 2 and 28 days of intervention. The primary analysis involved the comparison between SynΩ3 and placebo. In addition, SynΩ3 was compared to fish oil. The synbiotic SynΩ3 comprising Bacillus megaterium DSM 32963 and n-3 PUFA salts significantly increased circulating SPM precursor levels, including 18-hydroxy-eicosapentaenoic acid (18-HEPE) plus 5-HEPE, which was not achieved to this extent by fish oil with a similar n-3 PUFA content. Omega-3 indices were increased slightly by both SynΩ3 and fish oil. These findings suggest reconsidering conventional n-3 PUFA supplementation and testing the effectiveness of SynΩ3 particularly in conditions related to inflammation.

Acute pharmacodynamic responses to sitagliptin: Drug-induced increase in early insulin secretion in oral glucose tolerance test.

DPP4 inhibitors are widely prescribed as treatments for type 2 diabetes. Because drug responses vary among individuals, we initiated investigations to identify genetic variants associated with the magnitude of drug responses. Sitagliptin (100 mg) was administered to 47 healthy volunteers. Several endpoints were measured to assess clinically relevant responses - including the effect of sitagliptin on glucose and insulin levels during an oral glucose tolerance test (OGTT). This pilot study confirmed that sitagliptin (100 mg) decreased the area under the curve for glucose during an OGTT (p = 0.0003). Furthermore, sitagliptin promoted insulin secretion during the early portion of the OGTT as reflected by an increase in the ratio of plasma insulin at 30 min divided by plasma insulin at 60 min (T30:T60) from mean ± SEM 0.87 ± 0.05 to 1.62 ± 0.36 mU/L (p = 0.04). The magnitude of sitagliptin's effect on insulin secretion (as judged by the increase in the T30:T60 ratio for insulin) was correlated with the magnitude of sitagliptin-induced increase in the area under the curve for intact plasma GLP1 levels during the first hour of the OGTT. This study confirmed previously reported sex differences in glucose and insulin levels during an OGTT. Specifically, females exhibited higher levels of glucose and insulin at the 90-180 min time points. However, we did not detect significant sex-associated differences in the magnitude of sitagliptin-induced changes in T30:T60 ratios for either glucose or insulin. In conclusion, T30:T60 ratios for insulin and glucose during an OGTT provide useful indices to assess pharmacodynamic responses to DPP4 inhibitors.

Pharmacokinetic Interactions Between Tegoprazan and the Combination of Clarithromycin, Amoxicillin and Bismuth in Healthy Chinese Subjects: An Open-Label, Single-Center, Multiple-Dosage, Self-Controlled, Phase I Trial.

BACKGROUND: Tegoprazan is a potassium-competitive acid blocker that inhibits gastric acid and which may be used for eradicating Helicobacter pylori. This study focuses on the pharmacokinetic interaction and safety between tegoprazan and the combination of clarithromycin, amoxicillin and bismuth in healthy Chinese subjects. METHODS: An open-label, three-period, single-center, multiple-dosage, single-sequence, phase I trial was conducted in 22 healthy subjects. In period 1, the subjects took tegoprazan 50 mg twice daily for 7 days, and in period 2 they were administered clarithromycin 500 mg, amoxicillin 1000 mg and bismuth potassium citrate 600 mg twice daily for 7 days (days 14-20). Tegoprazan, clarithromycin, amoxicillin and bismuth potassium citrate were then administered in combination for 7 days (days 21-27) in period 3. Blood samples were collected up to 12 h after the last dose of each period. Safety assessments were performed in each period. RESULTS: The geometric mean ratios (GMRs) [90% confidence interval (CI)] of maximum plasma concentration at steady state (Cmax,ss) and area under the plasma concentration-time curve over the dosing interval (AUCτ) at steady state were 195.93% (175.52-218.71%) and 287.54% (263.28-314.04%) for tegoprazan and 423.23% (382.57-468.22%) and 385.61% (354.62-419.30%) for tegoprazan metabolite M1, respectively. The GMRs (90% CI) of Cmax,ss and AUCτ were 83.69% (77.44-90.45%) and 110.30% (102.74-118.41%) for clarithromycin, 126.25% (114.73-138.93%) and 146.94% (135.33-159.55%) for 14-hydroxyclarithromycin, 75.89% (69.73-82.60%) and 94.34% (87.94-101.20%) for amoxicillin, and 158.43% (125.43-200.11%) and 183.63% (156.42-215.58%) for bismuth, respectively. All reported adverse events were mild. The frequency of adverse events during the coadministration stage was not higher than that during the single- or triple-drug administration stages. CONCLUSION: The plasma exposure of tegoprazan, M1, 14-hydroxyclarithromycin and bismuth was increased after the coadministration of tegoprazan, clarithromycin, amoxicillin and bismuth. The coadministration exhibited favorable safety and tolerability. CLINICAL TRIALS REGISTRATION: CTR20230643.

Measurement proprieties of the CROM instrument for assessing head posture, neck retraction and protraction.

BACKGROUND: The CROM instrument is widely used clinically and in research to measure neck range of motion. However, its measurement proprieties during the assessment of protraction and retraction movements were not examined so far. OBJECTIVE: To analyse the intra- and inter-rater reliability, the concurrent validity of the CROM for measuring head posture, retraction and protraction in healthy subjects. METHODS: Thirty-three asymptomatic subjects were recruited and assigned in a random order to one of two raters. After a 10-min break, they were examined by a second rater (Assessment 1). After a 30-min break, both raters repeated the examination (Assessment 2). The examination consisted of measuring the head posture, maximum head protraction and maximum retraction. Each movement was repeated 3 times and measured simultaneously with the CROM and with a 3D capture system laboratory. RESULTS: The intra-rater reliability of the CROM was excellent for both raters for head posture and all head movements (ICC>0.9, 95% CI: 0.82-0.99, p < 0.01). The inter-rater reliability was excellent for head posture (ICC>0.95, 95% CI: 0.92-0.98, p < 0.01) and good-to-excellent for all movements at both time-points (ICC = 0.73-0.98, 95%CI: 0.45-0.99, p < 0.01). The validity analysis showed moderate-to-strong correlation between instruments for the head posture and head movements [(r) = -0.47 to -0.78), 95% CI: 0.99 to -0.24, p < 0.01]. CONCLUSION: The CROM instrument has good-to-excellent reliability and adequate validity for measuring cervical position and displacement in the sagittal plane.

Comparison of Full-Field Stimulus Threshold Measurements in Patients With Retinitis Pigmentosa and Healthy Subjects With Dilated and Nondilated Pupil.

Purpose: The common protocol of full-field stimulus threshold (FST) testing recommends pupil dilation. The aim of this study is to investigate the difference between FST measurements with dilated and nondilated pupils in healthy subjects and patients with retinitis pigmentosa (RP). Methods: Twenty healthy subjects and 20 RP patients were selected. One pupil of each subject was dilated; the other eye was measured in physiological width of the pupil. The FST was conducted using Diagnosys Espion E2/E3 with white, blue, and red stimuli. Statistical analysis was conducted with a mixed-model analysis of variance and a paired t-test. Results: The statistical analysis revealed a significant difference between measurements of dilated and nondilated pupils with the following: blue stimuli for all subjects and groups except those with highly progressed RP; white stimuli for all tested subjects in total, for RP patients with better-preserved visual field (VF), and rod-mediated FST response; and red stimuli for RP patients with better-preserved VF and rod-mediated FST response. On average, the difference between the FST values for RP patients were -3.2 ± 3 dB for blue, -2.3 ± 2.9 dB for white, and -0.83 ± 3 dB for red stimuli. The correlation between the FST values of dilated and nondilated pupils with all three stimuli was linear. Conclusions: Current recommendations are to perform FST with dilated pupils. However, based on this study's findings, pupil dilation can be omitted for clinical diagnostics or rough follow-ups. Translational Relevance: Our data provide useful information for the clinical use of FST.