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Background Intradialytic hypotension (IDH) and subsequent tissue damage may contribute to the poor outcome of chronic haemodialysis (HD) patients. While the IDH-incidence is lower in high-volume haemodiafiltration (HV-HDF) than in standard HD (S-HD), survival is better in HV-HDF. Tissue injury, as measured by extracellular vesicle (EV)-release, was compared between four modalities. Methods Forty chronic patients were cross-over randomized to S-HD, cool-HD (C-HD), low-volume HDF (LV-HDF), and HV-HDF. Blood pressure was recorded every 15 minutes. EVs from circulating blood-cell-elements (bio-incompatibility-related) and cardiovascular (CV) tissues (CV-related), were measured before and after dialysis. The influence of modalities and IDH on the rate of change of EVs was assessed. Both crude and haemoconcentration-adjusted analyses were performed. Results Leukocyte and erythrocyte-derived EVs increased in all modalities. Platelet-derived EVs increased more in LV-HDF and HV-HDF (68.4 respectively 56.1 × 106/ml) than in S-HD (27.5 × 106/ml), P values for interaction were <.01 respectively.06. Endothelial-derived CD144+ (2.3 × 106/ml in HV-HDF and 9.8 × 106/ml in S-HD) and cardiomyocyte-derived Connexin-43+ (12.0 respectively 31.9 × 106/ml) EVs increased less in HV-HDF than in S-HD (P for interaction.03 respectively.06). Correction for haemoconcentration attenuated all changes, although the increase in platelet-derived EVs remained significant in LV-HDF and HV-HDF, and CD144+ and Connexin-43+ EVs increased most in S-HD. EV release was similar in patients with varying IDH susceptibility and in sessions with and without IDH. Conclusions Most EVs increase during HD and HDF. Regarding platelet-derived EVs, HDF appears less biocompatible than HD. Considering CV-related EVs, tissue injury seems less pronounced in HV-HDF. The finding that EV release is IDH-independent needs confirmation. [ABSTRACT FROM AUTHOR]

Background and Aims: Needle injection and needle-free injection were proven effective in improving glycated hemoglobin (HbA1c) in type 2 diabetes mellitus (T2DM) patients. However, it is unclear if needle-free and needle injections of insulin during intensive insulin therapy in hospitalized patients provide similar efficacy and safety benefits. Methods: A self-controlled cross-over study was conducted on 62 patients with T2DM who received intensive long-acting and short-acting insulin injections with or without needles. The 7-point blood glucose test was performed on the 6th day after insulin administration and the injection method switched on the 7th day of hospitalization. The difference was compared in 7-point blood glucose levels. Results: The blood glucose levels at fasting (mean difference=-1.09 ± 2.38mmol/L, 95% CI, -1.69 to -0.48, p=0.0007) and post-breakfast (-1.14 ± 3.02mmol/L, 95%CI, -1.91 to -0.37, p=0.004) were better when patients were receiving needle-free injections compared to when receiving a needle injection. Indeed, daily blood glucose fluctuation, which presented as the area under the curve of glycemia, was decreased in needle-free injection periods (-0.3.48 ± 9.64, 95%CI, -5.95 to -1.01, p=0.0065). There was no significant difference in the dose of long-acting insulin between the two injection methods (-0.32 ± 2.69, 95%CI, -0.99 to 0.37, p>0.05). The dose of fast-acting insulin during the needlefree period was lower than that of when patients received needle injections (-1.66 ± 6.45, 95%CI, -3.29 to -0.025, p<0.05). There was no significant difference in satisfaction between the two regimens (-0.59 ± 1.55,95%CI, -0.938 to 0.509, p=0.557), but there was a significant difference in pain experience, favoring needle-free injections (p < 0.001). Conclusion: Glycemia was better controlled by needle-free insulin injections in hospitalized T2DM patients subjected to intensive glycemic control. These patients also experienced less pain than when insulin was injected with a needle. [ABSTRACT FROM AUTHOR]

There are conflicting findings over the bioavailability of long‐chain n‐3 polyunsaturated fatty acids (n‐3 PUFA) from krill oil (KO) compared with fish oil (FO) in short‐ and long‐term studies. The aim of this study was to compare the effects of KO versus FO on the enrichment of molecular species of plasma phospholipids in young women following a 30‐day consumption of the n‐3 oils. Eleven healthy women aged 18–45 years consumed seven capsules of KO per day (containing a total of 1.27 g n‐3 PUFA) or five capsules of FO per day (total of 1.44 g n‐3 PUFA) for 30 days in a randomized crossover study, separated by at least a 30‐day washout period. Fasting blood samples were collected at day zero (baseline), day 15 and day 30 and analyzed by HPLC‐MS/MS for molecular species of phospholipids. Supplementation increased n‐3 PUFA in main phospholipids classes in both groups. After 30 days of supplementation, 35 out of 70 molecular species containing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPAn‐3) had a significantly greater concentration in KO group compared with the FO treated group. The majority (89%) of the differentiated molecular species were choline and ethanolamine ether‐phospholipids. These data reveal that analysis of plasma phospholipids following 30 days of consumption of KO (a marine oil rich in phospholipids, including ether phospholipids) resulted in an enrichment of n‐3 PUFA in molecular species of ether‐phospholipids compared with FO (a triacylglycerol‐rich marine oil). [ABSTRACT FROM AUTHOR]

Abstract Background The possible effect of transcranial direct current stimulation (tDCS) in improving cognitive function is clear from studies involving pre-dementia stage mild cognitive impairment (MCI). However, the application of tDCS in actual clinical practice entails repeated hospital visits almost every day for treatment. The objective of this study is to confirm the possibility of self-application of tDCS at home by elderly patients with declined cognitive function and the significant clinical effect of tDCS administered at home. Methods/design This study will be conducted in 20 elderly people aged 60 to 80 years with complaints of subjective memory impairment while maintaining general functions with limited activities of daily living. This study involves a cross-over design that will include 2-week active or sham stimulation of both dorsolateral prefrontal cortexes (left, anode; right, cathode) randomly with a 2-week wash-out phase. Changes in cognitive function will be evaluated using visual recognition tasks and neuropsychological tests. In this study, tDCS will be carried out by each patient at his/her home and its safety and suitability will be evaluated. Discussion In this study, patients will apply a portable tDCS, developed for home use, for more than 2 weeks. Such studies can contribute to the use of tDCS as a realistic therapy. In addition, the utility of home-based tDCS will be confirmed by application of tDCS at home by the elderly with declined cognitive function. Furthermore, confirmation of tDCS as a significant therapeutic method can facilitate treatment of Alzheimer’s dementia at an early stage, including MCI. Trial registration Clinical Research Information Service (CRIS), KCT0002721. Registered on 9 March 2018.

Retrospective chart reviews have reported hypophosphatemia associated with elemental formula use in infants and children with systemic disease involving multiple diagnoses. The present study aims to evaluate the bioavailability of phosphorus from 2 commercial elemental formulas and to test our hypothesis of bioequivalence of the 2 products in healthy volunteers receiving gastric acid-suppressive medication. A single-center, double-blind, randomized, cross-over study was conducted in healthy volunteers with esomeprazole-induced hypochlorhydria. After a standardized low phosphorus meal followed by overnight fasting, subjects consumed 1 gram of phosphorus in a single oral dose of 1217 kcal of Product A (Neocate) or Product B (Elecare). The alternate product was given following a 1-week washout period. Blood and urine were collected at baseline and different time-points for up to 6 hours after product consumption. Area-under-the-curve (AUC) and peak values (C peak) for serum phosphate and calcium and urinary creatinine-corrected phosphate and calcium were assessed for bioequivalence of Products A and B. Results show that the geometric mean ratio (GMR) and 90% CI for serum phosphate were 1.041 (0.998-1.086) and 1.020 (0.963-1.080) for AUC 0-360 and C peak , respectively, meeting the predetermined criteria for bioequivalence. Urinary creatinine-corrected phosphate followed a similar pattern after intake of Product A and B, but did not reach bioequivalence criteria (GMR: AUC 70-370 = 1.105 (0.918-1.330); C peak = 1.182 (1.040-1.343)). Serum calcium concentrations (GMR: AUC 0-360 = 1.002 (0.996-1.009); C peak = 0.991 (0.983-0.999)) and urinary creatinine-corrected calcium excretion (GMR: AUC 70-370 = 1.117 (1.023-1.219); C peak = 1.157 (1.073-1.247)) demonstrated bioequivalence of the products. In conclusion, both elemental infant formulas showed equivalent serum phosphorus and calcium bioavailability in healthy volunteers even if combined with treatment with acid-suppressive medication. [ABSTRACT FROM AUTHOR]

The purpose of this pilot study was to examine the impact of animal-assisted intervention (AAI) on ambulation, physiologic stability, patient satisfaction, and perceived benefit in hospitalized pediatric heart transplant patients. This pilot study used a two-period, two-sequence cross-over design. Using a convenience sample of heart transplant patients between the ages six and nineteen, each subject participated in one AAI and one non-AAI study session over one week. All study sessions started with an aspect of walking. Three males and two females participated. Average age was 15 years. Subjects walked on average 1906 ft during the AAI session as compared to 1933 ft in the non-AAI session. Subjects spent a longer time (17 min) walking in the AAI session as compared to the non-AAI session (15 min). Blood pressure and respiratory rates remained stable. All subjects reported they liked working with the dog. Eighty percent of subjects actively engaged in physical contact and communication with the dog. No safety-related adverse events were reported. AAI may assist adolescent heart transplant patients to be more motivated to participate in therapeutic ambulation when walking with a dog. Further studies are needed to identify successful recruitment strategies in this highly vulnerable patient population. Many clinical challenges exist in implementing AAI research in the pediatric heart transplant population. A conceptual model is introduced to better understand the methodological challenges of conducting AAI research in the hospital setting. Key components include research, organizational, AAI, subject and time factors. • Caring for heart transplant patients can be challenging for the healthcare team. • AAI may help engage pediatric heart transplant patients in therapeutic ambulation. • Many methodological challenges exist in implementing AAI research in the CVICU. [ABSTRACT FROM AUTHOR]

Background: The possible effect of transcranial direct current stimulation (tDCS) in improving cognitive function is clear from studies involving pre-dementia stage mild cognitive impairment (MCI). However, the application of tDCS in actual clinical practice entails repeated hospital visits almost every day for treatment. The objective of this study is to confirm the possibility of self-application of tDCS at home by elderly patients with declined cognitive function and the significant clinical effect of tDCS administered at home.Methods/design: This study will be conducted in 20 elderly people aged 60 to 80 years with complaints of subjective memory impairment while maintaining general functions with limited activities of daily living. This study involves a cross-over design that will include 2-week active or sham stimulation of both dorsolateral prefrontal cortexes (left, anode; right, cathode) randomly with a 2-week wash-out phase. Changes in cognitive function will be evaluated using visual recognition tasks and neuropsychological tests. In this study, tDCS will be carried out by each patient at his/her home and its safety and suitability will be evaluated.Discussion: In this study, patients will apply a portable tDCS, developed for home use, for more than 2 weeks. Such studies can contribute to the use of tDCS as a realistic therapy. In addition, the utility of home-based tDCS will be confirmed by application of tDCS at home by the elderly with declined cognitive function. Furthermore, confirmation of tDCS as a significant therapeutic method can facilitate treatment of Alzheimer's dementia at an early stage, including MCI.Trial Registration: Clinical Research Information Service (CRIS), KCT0002721 . Registered on 9 March 2018. [ABSTRACT FROM AUTHOR]

Background: Cleansing the teeth with a toothbrush and paste is an indubitable mechanical plaque control method practiced by almost everyone. Eliminating dental plaque is an essential, fundamental and mandatory step to prevent the occurrence of periodontal diseases that are rife globally. The aim of the present study is to compare the antiplaque effectiveness of a prepared herbal and commercially available dentifrice. Materials and Methods: Thirty healthy individuals within the age group of 18–25 years were recruited to participate in the study. After achieving induced gingivitis and measuring plaque levels using Turesky modification of the Quigley Hein Plaque index in all the subjects, they were randomly divided into test arms A and B. Commercial dentifrice was distributed to one group, whereas the other group received prepared herbal dentifrice. Supervised brushing was carried out for 5 min, and plaque amounts after brushing were noted. After a washout period of 1 week, the same steps were repeated as per the cross-over study protocol. Unpaired t-test and paired t-tests were employed with P < 0.05. Results: Both the toothpastes show the difference in plaque scores immediately after brushing when compared to baseline and was statistically significant (P = 0.001). The mean plaque scores of commercial dentifrice (1.93 ± 1.52) were less than that of the prepared herbal dentifrice (2.35 ± 1.39) after brushing. Conclusion: The prepared herbal dentifrice had good antiplaque action. However, the plaque inhibitory action of self-prepared herbal toothpaste was marginally less when compared to commercial dentifrice. [ABSTRACT FROM AUTHOR]

In order to better understand the variability of pharmacodynamic and pharmacokinetic profiles of terfenadine between the previous studies as well as to qualitatively and quantitatively examine the proarrhythmic potential of its major active metabolite fexofenadine in comparison with that of terfenadine, we directly compared their electropharmacological effects with halothane-anesthetized dogs (n = 3). For this purpose, we adopted a cross-over design, which can directly compare the effects of terfenadine and fexofenadine under the identical metabolic condition. Terfenadine in doses of 0.03 and 0.3 mg/kg increased the mean blood pressure, but that of 3 mg/kg decreased it. Terfenadine also increased the heart rate and ventricular contractility in a dose-related manner; but delayed the atrioventricular nodal and intraventricular conductions as well as repolarization suggesting its proarrhythmic potential. Meanwhile, fexofenadine in the same dose increased the mean blood pressure in a dose-related manner without affecting any of the electrophysiological variables in the same animals that proarrhythmic risk of terfenadine was confirmed, indicating its lack of proarrhythmic risk. Peak plasma concentrations for fexofenadine were 3.7, 8.1 and 11.2 times greater than for terfenadine at each matching dose, indicating terfenadine may be metabolized much faster than fexofenadine. Taken together, after the low and middle doses of terfenadine, vasopressor effect of a metabolite fexofenadine could be greater than the depressor effect of parent compound terfenadine, but its reverse would be correct after the high dose. Thus, the cross-over analysis can be an effective way to better understand drug-induced cardiovascular responses. [ABSTRACT FROM AUTHOR]

Introduction: During hemodialysis (HD) the interaction of the blood with the dialyzer triggers both an inflammatory reaction and an activation of the coagulation cascade. An accepted parameter to quantify the extent of coagulation activation during HD is not available. This study aims to evaluate its amplitude, comparing dialyzers made of different polysulfone polymers, by measuring D-dimers in the filter-rinsing fluids (Frf) and to test whether Frf D-dimers are suitable candidate markers to assess contact coagulation activation during HD. Methods: In a prospective, cross-over study 41 hemodialysis patients were randomly allocated to nine HD sessions with three types of polysulfone membranes: Filter A: Poliflux®RevaclearMAX; Filter B: Helixone®Fx80, Filter C: Polyflux®H210. Findings: A total of 117 HD sessions were studied. The mean (SD) filter (Frf) D-dimers were 0.19 µg/L (0.56) for Filter A; 0.66 µg/L (2.81) for Filter B; 0.33 µg/L (1.13) for Filter C. Significant differences were found: A vs. B (P < 0.01), A vs. C (P = 0.01); B vs. C not significant. A large between-patient variability of D-dimer filter levels was found. D-Dimers in blood showed a similar trend but differences were not significant. Discussion: The contact activation of coagulation during HD may also vary among filters made up with similar polysulfones. D-dimer in the filter rinsing fluid but not in the blood can be considered a candidate marker for the evaluation of thrombogenicity during HD. Further studies are needed to elucidate the mechanism(s) and to confirm the usefulness of filter rinsing fluid D-Dimers as a clotting activation marker during HD. [ABSTRACT FROM AUTHOR]

Background and Aims: Needle injection and needle-free injection were proven effective in improving glycated hemoglobin (HbA1c) in type 2 diabetes mellitus (T2DM) patients. However, it is unclear if needle-free and needle injections of insulin during intensive insulin therapy in hospitalized patients provide similar efficacy and safety benefits., Methods: A self-controlled cross-over study was conducted on 62 patients with T2DM who received intensive long-acting and short-acting insulin injections with or without needles. The 7-point blood glucose test was performed on the 6th day after insulin administration and the injection method switched on the 7th day of hospitalization. The difference was compared in 7-point blood glucose levels., Results: The blood glucose levels at fasting (mean difference=-1.09 ± 2.38mmol/L, 95% CI, -1.69 to -0.48, p=0.0007) and post-breakfast (-1.14 ± 3.02mmol/L, 95%CI, -1.91 to -0.37, p=0.004) were better when patients were receiving needle-free injections compared to when receiving a needle injection. Indeed, daily blood glucose fluctuation, which presented as the area under the curve of glycemia, was decreased in needle-free injection periods (-0.3.48 ± 9.64, 95%CI, -5.95 to -1.01, p=0.0065). There was no significant difference in the dose of long-acting insulin between the two injection methods (-0.32 ± 2.69, 95%CI, -0.99 to 0.37, p>0.05). The dose of fast-acting insulin during the needle-free period was lower than that of when patients received needle injections (-1.66 ± 6.45, 95%CI, -3.29 to -0.025, p<0.05). There was no significant difference in satisfaction between the two regimens (-0.59 ± 1.55,95%CI, -0.938 to 0.509, p=0.557), but there was a significant difference in pain experience, favoring needle-free injections (p < 0.001)., Conclusion: Glycemia was better controlled by needle-free insulin injections in hospitalized T2DM patients subjected to intensive glycemic control. These patients also experienced less pain than when insulin was injected with a needle., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wu, Deng, Wang, Yu, Wang, Sun, Pan and Guo.)

Physical activity (PA) would increase the inhalation rate and thereby inhaled dose of air pollutants. However, it's still uncertain whether the effects of air pollutants on lung function are attenuated by PA, especially in the high-polluted areas. We aimed to disentangle the interaction between air pollution and PA on lung function among healthy adults. In this study, a real-world crossover study was conducted among 74 healthy adults. Each participant underwent both rest and 15-min intermittent moderate PA exposure scenarios (consisting of 15min stationary bike riding alternating with 15min of rest), which lasted for 2 h. On the same day, the participants among active and inactive group were exposed to the same air pollution. We have monitored the fine particulate matter (PM 2.5), particulate matter less than 10 μm (PM 10), particulate matter less than 1 μm (PM 1), black carbon (BC), nitrogen dioxide (NO 2), and ozone (O 3) continuously during 2-h exposure. Lung function were measured at five times points for each visit (before, immediately, 3 h, 5 h, and 24 h after the 2-h exposure scenario). Mixed-effects models were applied to explore the effects of air pollution, PA, and their interaction on lung function. The participants had a mean (standard deviation (SD)) age of 19.9 (0.9) years. The average concentration [mean ± SD] of PM 2.5 , PM 10 , PM 1 , BC, NO 2 , and O 3 were 59.4 ± 45.1 μg/m3, 122.8 ± 109.0 μg/m3, 38.8 ± 29.2 μg/m3, 1.94 ± 1.17 μg/m3, 59.5 ± 26.6 μg/m3, and 74.0 ± 30.3 μg/m3, respectively. Overall, greater increasement in lung function were observed among active group compared with inactive group at all timepoints. In fully adjusted models, we observed the benefits of PA and detrimental effects of air pollutants on lung function. Our results suggested that PA, compared to rest, alleviated the detrimental effects of air pollutants on lung function. We also stressed the importance of timing of measurements for capturing association. In conclusion, our observations suggested that PA might alleviate the associations between various pollutant exposures and lung function, which would drive further research towards potential pathway. [Display omitted] • Interaction of PA and air pollution were explored by crossover design. • PA benefits to lung function, while air pollution had detrimental effects. • PA alleviated the associations between air pollution and lung function. • It's critical to capture the time point on the negative associations of air pollution. [ABSTRACT FROM AUTHOR]

Vitamin D is typically supplied in capsule form, both in trials and in clinical practice. However, little is known regarding the efficacy of vitamin D administered via oral sprays – a method that primarily bypasses the gastrointestinal absorption route. This study aimed to compare the efficacy of vitamin D3 liquid capsules and oral spray solution in increasing wintertime total 25-hydroxyvitamin D (25(OH)D) concentrations. In this randomised, open-label, cross-over trial, healthy adults (n 22) received 3000 IU (75 µg) vitamin D3 daily for 4 weeks in either capsule or oral spray form. Following a 10-week washout phase, participants received the opposite treatment for a final 4 weeks. Anthropometrics and fasted blood samples were obtained before and after supplementation, with samples analysed for total 25(OH)D, creatinine, intact parathyroid hormone and adjusted Ca concentrations. At baseline, vitamin D sufficiency (total 25(OH)D>50 nmol/l), insufficiency (31–49 nmol/l) and clinical deficiency (<30 nmol/l) were evident in 59, 23 and 18 % of the participants, respectively. Overall, baseline total mean 25(OH)D concentration averaged 59·76 (sd 29·88) nmol/l, representing clinical sufficiency. ANCOVA revealed no significant difference in the mean and standard deviation change from baseline in total 25(OH)D concentrations between oral spray and capsule supplementation methods (26·15 (sd 17·85) v. 30·38 (sd 17·91) nmol/l, respectively; F=1·044, adjusted r2 0·493, P=0·313). Oral spray vitamin D3 is an equally effective alternative to capsule supplementation in healthy adults. [ABSTRACT FROM AUTHOR]

Purpose The aim of this clinical investigation was to identify and quantify the microbial species adhering to toothbrush bristles after controlled brushing and storage in different antimicrobial agents. Methods Sixteen healthy participants were enrolled in this study and randomly submitted to 4 interventions in a cross-over design: brushing and toothbrush storage in (I) Periogard/(II) Periobio (Chlorhexidine gluconate 0.12%), (III) Cepacol (cetylpyridinium chloride 0.05%) and (IV) distilled water (positive control). Thirty-eight bacterial species including putative pathogens and 5 Candida spp. were assessed by Checkerboard DNA-DNA hybridization. Results The results of the study have shown a striking reduction of the total microbial counts, including bacteria and Candida spp., on the toothbrush bristles after storage in cetylpyridinium chloride 0.05% ( p < 0.0001). Chlorhexidine gluconate 0.12% showed no differences on the total bacterial count when compared to distilled water ( p > 0.05). Cetylpyridinium chloride solution also presented the lowest genome counts and frequency of detection for individual target species; distilled water showed the highest individual genome counts ( p < 0.05). Potential pathogenic species were recorded in moderate to high levels for chlorhexidine gluconate and distilled water. Conclusion Cetylpyridinium chloride 0.05% was the most effective storage solution in the reduction of total and individual microbial counts, including pathogenic species. [ABSTRACT FROM AUTHOR]

Orlistat is a non-systemic treatment for obesity. The drug inhibits lipase in the gastrointestinal track mainly in the lumen of the stomach and small intestine by binding reversibly with the active site of gastric and pancreatic lipases, preventing the absorption of ∼30-35% of dietary fat. The undigested triglycerides are not absorbed, resulting in a caloric deficit and positive effect in weight control. The objective of this study was to assess the bioequivalence of orlistat administered as a generic and reference capsule formulations using a pharmacodynamic end-point. A total of 60 healthy volunteers followed a 5-day run-in diet period to be accustomed to a low fat diet; subjects were then randomized to receive under fed conditions oral doses of orlistat (60 mg) 3-times daily for 10 days as the generic (Ranbaxy Laboratories) or reference (Alli™, GlaxoSmithKline) capsule formulations. Subjects followed a standardized diet (2500 kcal/day, ∼30% as fat) for the entire study. Feces were collected over the last 2 days of the run-in period (baseline) and over the last 5 days of the two treatment periods. The amount of fat in meals and feces were assayed using the validated FTIR method with a limit of detection of 1.00 g%, respectively. Fecal fat excretion over 24 h (FFE24SS, calculated as the amount of fat excreted in feces adjusted by the amount of fat ingested) was used as a pharmacodynamic end-point to assess the bioequivalence between the two orlistat formulations. An analyses of variance (ANOVA) was performed on the log-transformed FFE24SS parameter to establish bioequivalence of the generic product with respect to the innovator formulation. Mean FFE24SS values at baseline and after repeated oral administrations of the generic and innovator formulations of orlistat were 0.88%, 40.55% and 40.54%, respectively. The ratio of least-squares means (LSM) of FFE24SS of the generic to the innovator formulation was 101.90%, with 90% confidence intervals of 97.94-106.01%. Orlistat was well tolerated by subjects in both periods of study and no serious adverse events were observed during the study. In conclusion, mean FFE24SS values were used as pharmacodynamic end-points to assess bioequivalence between two formulations of orlistat. Results from this study suggest that the test formulation of Orlistat capsule is bioequivalent to the reference marketed Alli™ when administered to healthy volunteers as a multiple dose under fed conditions. [ABSTRACT FROM AUTHOR]

Background This study compares waist circumference (WC) measured using the World Health Organization (WHO) and National Institutes of Health (NIH) protocols to determine if the results differ signi?? cantly, and whether equations can be developed to allow comparison between WC taken at the two different measurement sites. Data and Methods Valid WC measurements using the WHO and NIH protocols were obtained for 6,306 respondents aged 3 to 79 from Cycle 2 of the Canadian Health Measures Survey. Linear regression was used to identify factors associated with the difference between the NIH and WHO values. Separate prediction equations by sex were generated using WC_NIH as the outcome and WC_WHO and age as independent variables. Sensitivity and speci?? city were calculated to examine whether health risk based on the WC_WHO and on WC_NIH predicted measurements agreed with estimates based on WC_NIH actual measured values. Results For adults and children, WC_NIH signi?? cantly exceeded WC_WHO (1.0 cm for boys, 2.1 cm for girls, 0.8 cm for men and 2.2 cm for women). Predicted NIH values were statistically similar to measured values. Sensitivity (86% to 98%) and speci?? city (70% to 100%) values for health risk category based on the NIH predicted values were very high, meaning that respondents would be appropriately classi?? ed when compared with actual measured values. Interpretation The prediction equations proposed in this study can be applied to historical datasets to compare estimates based on WC data measured using the WHO and NIH protocols. [ABSTRACT FROM AUTHOR]

The study aim was to address the need for objective markers of pain-modifying interventions by testing the hypothesis that selective gait measures of knee joint loading can distinguish differences between non-steroidal anti-inflammatory (NSAID), analgesic treatment (opioid-receptor agonist), and placebo in patients medial knee osteoarthritis (OA). A randomized, single-blind washout, double-blind treatment, double-dummy cross-over trial using three treatment arms placebo, opioid (Oxycodone), and NSAID (Celecoxib) in medial compartment knee OA patients. Six patients with Kellgren-Lawrence radiographic severity grades of 2 or 3 completed six testing sessions (gait and pain assessment) at 2-week intervals. A significant increase was found in the knee total reaction moment and vertical ground reaction force (GRF) for Celecoxib compared to placebo ( p = 0.005, p = 0.003), but not for Oxycodone compared to placebo ( p = 0.20, p = 0.27) treatments. Walking speed was significantly higher for the Celecoxib and Oxycodone compared to placebo treatment ( p = 0.041 and p = 0.031, respectively). Self-reported function (WOMAC scores) was not different among treatments ( p > 0.05). The changes in total reaction moments and GRFs for only the NSAID suggest that greater increases in joint loading occurs when joint inflammation is treated in addition to pain. The total knee reaction moment, representing the magnitude of the extrinsic moment, appears to be a sensitive marker, more so than self-reported metrics, for evaluating knee OA treatment effects. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1118-1124, 2012 [ABSTRACT FROM AUTHOR]

Abstract: Objective: Nasal mucociliary clearance, which plays an important role in defending the respiratory system, tends to decrease under conditions of low relative humidity (RH). The purpose of this randomized cross-over study was to investigate the preventive effect of prehydration on nasal mucociliary clearance under low RH conditions. Methods: Fourteen young healthy subjects were assigned to three interventions: prehydration (6ml/kg body weight) using water (W), prehydration using a carbohydrate–electrolyte beverage (CE), and control conditions (Cont) with no prehydration. For each intervention trial, subjects sat for 4h in an environmental chamber (23°C, 10% RH). Nasal mucociliary clearance was measured by the saccharin transit time (ST). Furthermore, a dry sensation of the mucosa, urine volume, and body weight were measured at the baseline, 2h and 4h after entering the environmental chamber, respectively. Results: ST was prolonged under the Cont conditions after entering the environmental chamber. Prehydration with CE led to a significantly lower ST compared to the Cont pretreatment at 2h, whereas the W trial showed no significance difference in comparison to the Cont values. Conclusion: These results suggest that prehydration with a carbohydrate–electrolyte beverage is therefore beneficial for maintaining better nasal mucociliary clearance at least for 2h under low RH conditions. [Copyright &y& Elsevier]

Purpose: The aim of this study was to compare the influence of triangular and envelope flaps on trismus, pain, and facial swelling after mandibular third molar surgery. Methods: Twenty healthy patients with bilateral, symmetrically impacted mandibular third molars were included in this double-blinded, prospective, cross-over, randomized study. The patients were operated with envelope flap on one side and triangular flap on the other side. Trismus was determined by measuring maximum interincisal opening, and facial swelling was evaluated using a tape measuring method. Pain was determined using visual analog scale (VAS) and recording the number of pain pills taken. Results: The facial swelling measurements and VAS scores were lower in the envelope flap group compared to the triangular flap group. There was no significant difference between the two flap designs in operation time, maximum interincisal opening, and the number of analgesics taken. Conclusion: Envelope flap yields to less facial swelling and reduced VAS scores in comparison to triangular flap. There is no clinical difference in trismus between the two flap designs. Despite the higher VAS scores with triangular flap, no additional doses of analgesics were required in triangular flap. [ABSTRACT FROM AUTHOR]

Abstract: Objective: This study aimed to evaluate the effects of statin therapy on serum levels of antibodies to several specific heat shock proteins (HSPs) in dyslipidemic patients. Design and methods: Participants (n =102) were treated with simvastatin (40mg/day), or placebo in a randomized, double-blind, placebo-controlled, cross-over trial. Anti-HSP60, 65, 70, and hs-CRP levels were measured before and after each treatment period. Seventy-seven subjects completed the study. Results: Treatment with simvastatin was associated with significant reductions in serum anti-HSP60, 65, and 70 titers in the dyslipidemic patients (10%, 14%, and 15% decrease, respectively) (p <0.001). There have been previous reports of reductions in serum CRP with statin treatment, and although median CRP levels were 9% lower on simvastatin treatment, this did not achieve statistical significance. Conclusion: While it is unclear whether HSP antibodies are directly involved in atherogenesis, our findings suggest that simvastatin inhibits autoimmune responses that may contribute to the development of cardiovascular disease. [Copyright &y& Elsevier]

Objectives: The tolerability and efficacy of lanthanum carbonate has not been studied in the Indian population. This study was, therefore, undertaken to compare the efficacy and tolerability of lanthanum carbonate with calcium acetate in patients with stage 4 chronic kidney disease. Design: A randomized open label two group cross-over study. Materials and Methods: Following Institutional Ethics Committee approval and valid consent, patients with stage 4 chronic kidney disease were randomized to receive either lanthanum carbonate 500 mg thrice daily or calcium acetate 667 mg thrice daily for 4 weeks. After a 4-week washout period, the patients were crossed over for another 4 weeks. Serum phosphorous, serum calcium, serum alkaline phosphatase, and serum creatinine were estimated at fixed intervals. Results: Twenty-six patients were enrolled in the study. The mean serum phosphorous concentrations showed a declining trend with lanthanum carbonate (from pre-drug levels of 7.88 ± 1.52 mg/dL-7.14 ± 1.51 mg/dL) and calcium acetate (from pre-drug levels of 7.54 ± 1.39 mg/dL-6.51 ± 1.38 mg/dL). A statistically significant difference was seen when comparing the change in serum calcium produced by these drugs (P < 0.05). Serum calcium levels increased with calcium acetate (from pre-drug levels of 7.01 ± 1.07-7.46 ± 0.74 mg dL), while it decreased with lanthanum carbonate (from pre-drug levels 7.43 ± 0.77-7.14 ± 0.72 mg/ dL). The incidence of adverse effects was greater with lanthanum carbonate. Conclusion: Lanthanum carbonate and calcium acetate are equally effective phosphate binders with trends obvious in the first 4 weeks of therapy. The decrease in serum calcium levels with lanthanum carbonate when compared to the increase in serum calcium levels due to calcium acetate is statistically significant. The drawback of lanthanum carbonate is its high cost and relatively higher incidence of adverse events during treatment. [ABSTRACT FROM AUTHOR]

Background: Glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs) decrease acute postoperative pain and hyperalgesia. The objectives of this study were to investigate the effects of methylprednisolone and ketorolac on hyperalgesia around a skin burn injury and on pressure pain thresholds. Methods: In a double-blind, placebo-controlled, randomized trial with cross-over design, methylprednisolone 125 mg, ketorolac 60 mg or placebo was administered intravenously in 12 male volunteers on three separate days at least 4 days apart. Primary and secondary hyperalgesia were produced by a first-degree burn injury on abdominal skin 45 min before injection of the test medicines. The area of secondary mechanical hyperalgesia outside the site of injury was measured. Pressure pain stimuli were applied on the base of a fingernail, increasing until the pressure pain detection threshold (PPDT) and pressure pain tolerance threshold (PPTT) were reached. Results: Compared with placebo, the active drugs reduced the area of secondary hyperalgesia (methylprednisolone, P < 0.001; ketorolac, P < 0.01). Ketorolac but not methylprednisolone increased PPDT compared with placebo ( P < 0.05). Both active drugs increased PPTT compared with placebo (methylprednisolone, P < 0.01; ketorolac, P < 0.001). Ketorolac increased PPTT more than methylprednisolone ( P < 0.05). Conclusions: Methylprednisolone and ketorolac increased PPTT attenuated secondary hyperalgesia around a skin burn injury. PPTT increased after both methylprednisolone and ketorolac. The present study demonstrates analgesic and anti-hyperalgesic properties of a glucocorticoid and a non-selective NSAID that have not been demonstrated previously in human subjects. [ABSTRACT FROM AUTHOR]

There are indications that both intensive exercise and electrical stimulation have a beneficial effect on arm function in post-stroke hemiplegic patients. We recommend the use of Functional Electrical Therapy (FET), which combines electrical stimulation of the paretic arm and intensive voluntary movement of the arm to exercise daily functions. FET was applied 30 min daily for 3 weeks. Forty-one acute hemiplegics volunteered in the 18-months single blinded cross-over study (CoS). Nineteen patients (Group A) participated in FET during their acute hemiplegia, and 22 patients (Group B) participated in FET during their chronic phase of hemiplegia. Group B patients were controls during FET in acute hemiplegia, and Group A patients were controls during the FET in chronic hemiplegia. Thirty-two patients completed the study. The outcomes of the Upper Extremity Function Test (UEFT) were used to assess the ability of patients to functionally use objects, as were the Drawing Test (DT) (used to assesse the coordination of the arm), the Modified Ashworth Scale, the range of movement, and the questionnaire estimating the patients' satisfaction with the usage of the paretic arm. Patients who participated in the FET during the acute phase of hemiplegia (Group A) reached functionality of the paretic arm, on average, in less than 6 weeks, and maintained this near-normal use of the arm and hand throughout the follow-up. The gains in all outcome scores were significantly larger in Group A after FET and at all follow-ups compared with the scores before the treatment. The gains in patients who participated in the FET in the chronic phase of hemiplegia (Group B) were measurable, yet not significant. The speed of recovery was larger during the period of the FET compared with the follow-up period. The gains in Group A were significantly larger compared with the gains in Group B. The FET greatly promotes the recovery of the paretic arm if applied during the acute phase of post-stroke hemiplegia. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine the effect of intermittent training in a hypobaric chamber on physical exercise at sea level. Over a 10 day period, 16 male triathletes trained for 2 h each day on a cycle ergometer placed in a hypobaric chamber. Training intensity was at 60%-70% of the heart rate reserve. There were 8 subjects who trained at a simulated altitude of 2,500 m, the other 8 trained at sea level. A year later, a cross-over study took place. Baseline measurements were made on a cycle ergometer at sea level, which included an incremental test until exhaustion and a Win-gate Anaerobic Test. Altogether, 12 subjects completed the cross-over study. At 9 days after training in hypoxia, significant increases were seen in maximal power output (Vmax)(5.2%), anaerobic mean power (4.1%), and an- aerobic peak power (3.8%). A non-significant increase in maximal oxygen uptake (V'O2max) of 1.9% was observed. At 9 days after training at sea level, no significant changes were seen in Vmax (2.1 %), V'O2max (2.0%), anaerobic mean power (0.2%) and anaerobic peak power (0.2%). When comparing the results of the two training regimes, the anaerobic mean power was the only variable that showed a significantly larger increase as a result of training at altitude. And, although the differences in percentage change between the two training protocols were not significant, they were substantial for Vmax as well as for anaerobic peak power. The results of this study indicate that intermittent hypobaric training can improve the anaerobic energy supplying system, and also, to a lesser extent, the aerobic system. It can be concluded that the overall results of the cross-over study showed predominantly improvements in the anaerobic metabolism at variance with the previous study of our own group, where the relative V'O2max and Vmax increased by 7%. [ABSTRACT FROM AUTHOR]

Background. Vancomycin is often administered during the last hour of haemodialysis because it was not removed significantly by older hemodialyzers. However, newer higher permeability hemodialyzers remove vancomycin, although the amount removed varies considerably between dialyzers. The purpose of this study was to determine the apparent amount of vancomycin removed during the last hour of haemodialysis with a CAHP‐210 hemodialyzer. [ABSTRACT FROM PUBLISHER]

A double-blind, randomized cross-over trial was carried out in 50 patients undergoing surgical removal of bilaterally impacted lower wisdom teeth. Surgery in each patient was performed twice and paracetamol 1000 mg was administered once preoperatively and once postoperatively. The time interval to additional analgesic intake and the pain intensity up to and at that time were assessed. There was no difference between the 2 treatments. It was concluded that preoperative paracetamol does not offer any clinical advantage in patients who undergo surgical removal of impacted lower wisdom teeth. [ABSTRACT FROM AUTHOR]

Aim: To compare plaque removal and wear between charcoal infused bristle toothbrushes (T1) and nylon bristle toothbrushes (T2) in a randomized clinical crossover study., Materials and Methods: A cross-over study was conducted in 2 phases of 6 weeks duration each with an intervening 2-week washout. Twenty-five participants meeting inclusion criteria were randomly allocated into groups A (13) and B (12). In phase 1: group A was assigned T1 and group B was assigned T2. Toothbrushing was advised twice daily for 2 minutes by modified bass technique after meals. At baseline, 3 weeks and 6 weeks the wear index (WI), plaque index (PI) and gingival index (GI) were recorded. Following washout in phase 2 group A was assigned T2 and group B was assigned T1 and the same study protocol was followed., Results: Intra-group comparison between baseline, 3 and 6 weeks by the paired t-test resulted in significant reduction in PI, GI and increase in WI ( p <0.05) for T1 and T2. Inter-group comparison using the unpaired t-test resulted in WI for T1 being significantly higher ( p <0.05) at 3 weeks and lower at 6 weeks ( p <0.05) compared to T2. PI for T1 was significantly higher at 3 weeks ( p <0.05) and lower at 6 weeks ( p <0.05) compared to T2. No significant difference in GI scores between T1 and T2 at 3 and 6 weeks was observed ( p >0.05)., Conclusion: Charcoal infused bristles demonstrated less wear and more plaque removal compared to nylon bristles., Clinical Significance: Charcoal infused bristles demonstrate less wear compared to nylon bristles.

Introduction: Spinal cord stimulation (SCS) is an established, effective method of treating chronic pain. High frequency stimulation (HFS) is an alternative SCS waveform that has been shown to alleviate pain but also necessitates more frequent recharging. The purpose of this pilot study is to evaluate efficacy of alternating conventional stimulation and HFS (termed "shuffle" stimulation) in improving SCS outcomes., Methods: Shuffle stimulation was designed to deliver conventional stimulation in upright positions with relative HFS in lying positions, automated through accelerometer technology. In this 13-week cross-over study, patients were randomized to receiving conventional and shuffle stimulation in four-week blocks. Pain outcomes and sensory testing were compared from preoperative baseline and at the conclusion of each study period., Results: Twelve patients completed this study. Two patients showed no change from baseline visual analogue scale (VAS) with either type of stimulation and were excluded from statistical analysis of pain outcomes. Mean numerical rating scale (NRS) scores assessing current pain were significantly lower in shuffle stimulation (4.0 ± 1.6) compared to conventional stimulation (5.8 ± 2.3) (p = 0.024). In the total cohort, 7 of 11 patients preferred shuffle over conventional stimulation., Conclusions: This study generated preliminary evidence showing improved NRS current pain scores in shuffle stimulation compared to conventional stimulation. More patients preferred shuffle stimulation compared to conventional stimulation. Optimizing stimulation when patients are recumbent may increase patient satisfaction and pain control. The potential advantages of shuffle stimulation may warrant further investigation., (© 2018 International Neuromodulation Society.)

In order to better understand the variability of pharmacodynamic and pharmacokinetic profiles of terfenadine between the previous studies as well as to qualitatively and quantitatively examine the proarrhythmic potential of its major active metabolite fexofenadine in comparison with that of terfenadine, we directly compared their electropharmacological effects with halothane-anesthetized dogs (n = 3). For this purpose, we adopted a cross-over design, which can directly compare the effects of terfenadine and fexofenadine under the identical metabolic condition. Terfenadine in doses of 0.03 and 0.3 mg/kg increased the mean blood pressure, but that of 3 mg/kg decreased it. Terfenadine also increased the heart rate and ventricular contractility in a dose-related manner; but delayed the atrioventricular nodal and intraventricular conductions as well as repolarization suggesting its proarrhythmic potential. Meanwhile, fexofenadine in the same dose increased the mean blood pressure in a dose-related manner without affecting any of the electrophysiological variables in the same animals that proarrhythmic risk of terfenadine was confirmed, indicating its lack of proarrhythmic risk. Peak plasma concentrations for fexofenadine were 3.7, 8.1 and 11.2 times greater than for terfenadine at each matching dose, indicating terfenadine may be metabolized much faster than fexofenadine. Taken together, after the low and middle doses of terfenadine, vasopressor effect of a metabolite fexofenadine could be greater than the depressor effect of parent compound terfenadine, but its reverse would be correct after the high dose. Thus, the cross-over analysis can be an effective way to better understand drug-induced cardiovascular responses.

Prostate specific membrane antigen (PSMA) is expressed in unfavorable prostate cancer. PSMA is basis for new diagnostics and theranostics. PET/CT using PSMA is more sensitive than choline PET/CT. 177 Lu-PSMA radioligand therapy is mainly used for patients with end-stage prostate cancer. This report describes a patient with a third recurrence in lymph nodes. The recurrence was treated with 177 Lu-PSMA radioligand therapy instead of chemotherapy with docetaxel. The effect was in part evaluated relative to that of two established salvage treatments. Prior salvage radiotherapy and abiraterone of the first and second recurrence in lymph nodes had given only a partial reduction of PSA. Nevertheless within five months of follow-up, 177 Lu-PSMA radioligand therapy of the third recurrence in lymph nodes reduced PSA for a period to unmeasurable levels. 177 Lu-PSMA radioligand therapy gave only mild adverse effects. In conclusion, for a patient with lymph node metastatic prostate cancer, 177 Lu-PSMA-617 radioligand therapy had an attractive therapeutic profile. A follow-up study of similar patients is being planned., Competing Interests: CONFLICTS OF INTEREST The authors have stated that they have no conflicts of interest.

Scope: We have recently shown that coenzyme Q10 (CoQ10) enhances macrophage reverse cholesterol transport via activator protein-1/miRNA-378/ABCG1 signal pathway in vivo and in vitro. Whether CoQ10 exerts similar beneficial effects in human is currently unknown. The present study evaluated the effect of CoQ10 on ABCG1-mediated macrophage cholesterol efflux in 20 healthy volunteers., Methods and Results: Participants were given 100 mg CoQ10 twice daily or placebo for 1 week with a 1-week washout period. Human monocyte-derived macrophages (MDMs) were differentiated under pooled sera obtained before (preCoQ10) or after CoQ10 (postCoQ10) consumption. The CoQ10-induced inhibition of MDMs foam cell formation was blocked by ABCG1 silencing in postCoQ10 MDMs incubated with postCoQ10 sera compared to preCoQ10 sera. The cholesterol efflux to HDL, and mRNA as well as protein expressions of ATP-binding cassette transporter G1 (ABCG1) were augmented in postCoQ10 MDMs incubated with postCoQ10 sera compared to preCoQ10 sera. The change in the serum CoQ10 concentration positively correlated with cholesterol efflux to HDL and ABCG1 mRNA level in the CoQ10 group. MDMs treated with purified CoQ10 had an enhanced cholesterol efflux to HDL., Conclusion: CoQ10 consumption may have an atheroprotective property by inducing ABCG1 expression and enhancing HDL-mediated macrophage cholesterol efflux in healthy individuals., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

An abstract of the article "Hyperacusis, sound annoyance, and loudness hypersensitivity in children," by Claudia Barros Coelho and Tanit Ganz Sanchez is presented.