2-week Washout Period Research Articles

Comparison between natural rubber knee support and sponge knee support on the protection of knee joint: A crossover randomized controlled study among patients with bleeding disorders.

Knee support, frequently made from sponge, is used to reduce injury. Sponge has less elasticity and durability compared with natural rubber. To our knowledge, there was no study that demonstrated the effectiveness of natural rubber and sponge in prevention of injury in children with bleeding disorders. The study aimed to demonstrate the effectiveness and satisfaction of natural rubber knee support compared with sponge knee support among children with bleeding disorders. The study consisted of threephases: (I) measuring reduced compression force, (II) producing size-appropriate knee support prototypes, and (III) conducting a randomized crossover trial, including 8 weeks wearing natural rubber knee support and sponge knee support with a 4-week wash-out period. The number of knee bleeds and user satisfaction were recorded. A better compression force reduction in natural rubber (60%) than sponge (12%) was demonstrated. Knee support comprised a body part, made from natural-stretchable cotton and a protection part, made from either natural rubber or sponge. They were produced in foursizes: S, M, L, and XL and appropriately applied to 42 patients (21 hemophilia, 21 platelet disorders) with a mean (SD) age of 7.0 (2.9) years. The results from randomization showed no significant difference in the number of knee bleeds between the two knee support groups (10 vs. 7, p = 0.37). In terms of satisfaction score, the natural rubber knee supports were more durable (45.2% vs. 23.8%, p = 0.04) and easier to use (28.5% vs. 14.3%, p = 0.03). In addition, a higher percentage of parents chose natural rubber knee support when compared with sponge knee supports (71.0% vs. 29.0%, p = 0.006). Natural rubber knee support showed comparable effectiveness in the prevention of knee bleeding but was superior to sponge knee support in compression force reduction and satisfaction.

Single-dose nonsteroidal anti-inflammatory drugs in horses have no impact on concentrations of cytokines or growth factors in autologous protein solution and platelet-rich plasma.

To determine the effects of a single dose of the NSAIDs phenylbutazone, firocoxib, flunixin meglumine, and ketoprofen on concentrations of growth factors and cytokines in autologous protein solution (APS) and platelet-rich plasma (PRP). 6 adult university-owned horses. For the first phase, 6 horses were randomized to receive ketoprofen (1,000 mg) or flunixin meglumine (500 mg) IV. Blood was obtained and processed for APS (Pro-Stride) and PRP (Restigen) before and 6 hours after administration of NSAIDs. Horses underwent a 2-week washout period, after which the protocol was repeated using a crossover design. For the second phase, following at least a 2-week washout period, the study protocol was repeated with phenylbutazone (1 g) or firocoxib (57 mg) administered orally. Plasma was collected 6 hours after administration for evaluation of drug concentrations, and APS and PRP were analyzed for concentrations of drug, platelets, leukocytes, and several growth factors and cytokines (PDGF, fibroblast growth factor, TGF-β1, IL-1β, IL-10, IL-6, IL-8, and tumor necrosis factor-α) before and 6 hours after administration of NSAIDs using immunoassays. There were no significant differences in concentrations of cytokines or growth factors before or after administration of any NSAID. There were significant differences in concentrations of leukocytes and platelets based on both product and time. NSAID concentrations in plasma were not significantly different from concentrations in APS and PRP. These results help guide clinicians on the appropriate use of these NSAIDs in conjunction with the processing of APS and PRP, which is unlikely to significantly alter the final product after single-dose administration.

Magnetic collars improve owner-reported pain scores in dogs with osteoarthritis in a blinded crossover study.

To investigate changes in owner-reported pain, interference of pain on function, and quality of life (QOL) in dogs with clinically suspected osteoarthritis when wearing a collar containing a static magnet. 16 dogs over 5 years old weighing between 10 and 40 kg with a clinical diagnosis of osteoarthritis and on stable treatment. A prospective, blinded crossover study in which dogs wore a collar containing a static magnet or placebo for two 4-week study arms separated by a 2-week washout period. Clients completed the Canine Brief Pain Inventory prior to collar placement and then weekly throughout each arm. Changes in QOL, pain severity, and pain interference scores from the beginning to the end of these arms and changes between the arms were calculated and analyzed using Wilcoxon signed rank tests. 40% of included dogs were on stable doses of NSAIDs. The pain severity scores (PSS), pain interference scores (PIS), and QOL scores were not significantly different at the start of the arms. There was no significant change in PSS or PIS from the start to end of the placebo arms (median changes, 0 and -0.1). Both PSS and PIS reduced significantly during the magnet arms (median changes, -1.0 and -1.2, respectively). The QOL scores did not change significantly in either arm (median changes, 0 and 0). This preliminary study suggests that magnetic collars reduce owner-reported pain severity and pain interference on function in dogs with clinically suspected osteoarthritis, and further, larger investigations are now warranted.

Defecation after magnesium supplementation enhances cognitive performance in triathletes

Constipation is correlated with diminished cognitive function, revealing a possible rectum-brain connection. In this counter-balanced crossover trial, 13 elite triathletes underwent a Stroop test to assess cognitive function and executive control. The Stroop test was conducted both with and without magnesium oxide intake, with a 1-week washout period between sessions. Oxygenation and blood distribution during the cognitive challenge were measured using Near-Infrared Spectroscopy (NIRS). Measurements were taken in both the prefrontal brain and the sub-navel region, where the highest glucose uptake was detected under the 18F-fluorodeoxyglucose Positron Emission Tomography (PET) scan. A significant reduction in completion time for the Stroop test was observed after defecation compared to the non-defecated condition (non-defecation: [27.1 ​± ​1.1] s; non-magnesium defecation: [24.4 ​± ​0.9] s; magnesium defecation: [23.4 ​± ​0.8] s, p ​< ​0.05). Stroop test performance was improved in all (100%, 13/13) of the participants after magnesium-induced defecation and most (69%, 9/13) of the participants after non-magnesium-induced defecation. While no alterations in oxygenation and blood distribution were observed in the prefrontal brain during the Stroop test, decreased oxygenation levels were observed in the sub-navel region under both defecated conditions, without significant changes in blood distribution (p ​< ​0.05). This data suggests an acute increase in oxygen consumption at this specific region. The result of this study suggests an unexplored causal link between the state of the rectum and cognitive performance. Magnesium supplementation to improved rectal emptying presents a novel application for optimizing cognitive function in athletes navigating intricate racing conditions.

Three-minute nebulization of gentamicin in healthy dogs results in therapeutic concentrations in bronchoalveolar lavage fluid while remaining below the toxic range values in blood.

To determine and compare the concentration of gentamicin in the lower airways and serum of healthy spontaneously breathing dogs after nebulization with 5% undiluted gentamicin during 3 versus 10 minutes. 10 healthy experimental Beagles. This was a prospective crossover study. A standardized bronchoalveolar lavage (BAL) procedure was performed in each dog after 1 week of administration of each of 2 different gentamicin nebulization protocols separated by a 1-week washout period. The 2 protocols consisted of nebulization of 5% undiluted gentamicin (50 mg/mL) twice daily either during 10 minutes per session (± 95 mg; 10-minute protocol) or 3 minutes per session (± 28 mg; 3-minute protocol). BAL fluid (BALF) was obtained under general anesthesia using a bronchoscope within 15 minutes after administration of the last nebulization. Blood was collected within 5 minutes after BALF collection. BALF and serum gentamicin concentrations were determined by particle-enhanced turbidimetric inhibition immunoassay. Concentrations between protocols were compared using a paired t test. Both BALF and serum gentamicin concentrations were higher after the 10-minute protocol compared with the 3-minute protocol (mean ± SD: 2.41 ± 0.87 mg/L vs 1.25 ± 0.31 mg/L, P = .001; and 1.02 ± 0.59 mg/L vs 0.31 ± 0.24 mg/L, P < .0001 in BALF and serum, respectively), while the BALF-to-serum ratio did not differ between the protocols (3.75 [1.37 to 5.75] (median [IQR]) in the 3-minute protocol vs 2.48 [2.02 to 2.67] in the 10-minute protocol; P = .754). A 3-minute nebulization of gentamicin seems to achieve sufficient concentrations of gentamicin in the BALF to have good efficacy against aminoglycoside-sensitive bacteria while remaining below the toxic range values in blood.

Effects of post-exercise cold-water immersion on performance and perceptive outcomes of competitive adolescent swimmers

PurposeTo evaluate the effects of repeated use of cold-water immersion (CWI) during a training week on performance and perceptive outcomes in competitive adolescent swimmers.MethodsThis randomized-crossover study included 20 athletes, who received each intervention [CWI (14 ± 1 °C), thermoneutral water immersion (TWI) (27 ± 1 °C) as placebo, and passive recovery (PAS)] three times a week between the land-based resistance training and swim training. The interventions were performed in a randomized order with a 1-week wash-out period. We tested athletes before and after each intervention week regarding swim (100 m freestyle sprints) and functional performance (flexibility, upper and lower body power, and shoulder proprioception). We monitored athlete’s perceptions (well-being, heaviness, tiredness, discomfort and pain) during testing sessions using a 5-item questionnaire. Athlete preferences regarding the interventions were assessed at the end of the study. We used generalized linear mixed models and generalized estimating equations for continuous and categorical variables, respectively (intervention x time).ResultsWe found a time effect for swim performance (p = .01) in which, regardless the intervention, all athletes improved sprint time at post-intervention compared to baseline. There was an intervention effect for pain (p = .04) and tiredness (p = .04), but with no significant post-hoc comparisons. We found no significant effects for other outcomes. All athletes reported a preference for CWI or TWI in relation to PAS.ConclusionThe repeated use of CWI throughout a training week did not impact functional or swim performance outcomes of competitive adolescent swimmers. Perceptive outcomes were also similar across interventions; however, athletes indicated a preference for both CWI and TWI.

Morning exercise and pre-breakfast metformin interact to reduce glycaemia in people with type 2 diabetes: a randomized crossover trial.

Exercise is recommended in the treatment of type 2 diabetes and can improve insulin sensitivity. However, previous evidence suggests that exercise at different times of the day in people with type 2 diabetes may have opposing outcomes on glycaemia. Metformin is the most commonly prescribed initial pharmacological intervention in type 2 diabetes, and may alter adaptions to exercise. It is unknown if there is an interaction between metformin and diurnal exercise outcomes. We aimed to investigate glycaemic outcomes of moderate intensity morning vs. evening exercise in people with type 2 diabetes being prescribed metformin monotherapy. In this study, nine males and nine females with type 2 diabetes undergoing metformin monotherapy (age 61±8.2years, mean±SD) completed a 16-week crossover trial including 2-week baseline recording, 6weeks randomly assigned to a morning exercise (07.00-10.00h) or evening exercise (16.00-19.00h) and a 2-week wash-out period. Exercise arms consisted of 30min of walking at 70% of estimated max heart rate every other day. Glucose levels were measured with continuous glucose monitors and activity measured by wrist-worn monitors. Food-intake was recorded by 4-day food diaries during baseline, first and last 2weeks of each exercise arm. There was no difference in exercise intensity, total caloric intake or total physical activity between morning and evening arms. As primary outcomes, acute (24h) glucose area under the curve (AUC), was lower (P=0.02) after acute morning exercise (180.6±68.4mmol/l) compared to baseline (210.3±76.7mmol/l); and there were no differences identified for glucose (mmol/l) between baseline, morning and evening exercise at any specific time point when data were analysed with two-way ANOVA. As secondary outcomes, acute glucose AUC was significantly lower (P=0.01) in participants taking metformin before breakfast (152.5±29.95mmol/l) compared with participants taking metformin after breakfast (227.2±61.51mmol/l) only during the morning exercise arm; and during weeks 5-6 of the exercise protocol, glucose AUC was significantly lower (P=0.04) for participants taking metformin before breakfast (168.8±15.8mmol/l), rather than after breakfast (224.5±52.0mmol/l), only during morning exercise. Our data reveal morning moderate exercise acutely lowers glucose levels in people with type 2 diabetes being prescribed metformin. This difference appears to be driven by individuals that consumed metformin prior to breakfast rather than after breakfast. This beneficial effect upon glucose levels of combined morning exercise and pre-breakfast metformin persisted through the final 2weeks of the trial. Our findings suggest that morning moderate intensity exercise combined with pre-breakfast metformin intake may benefit the management of glycaemia in people with type 2 diabetes. KEY POINTS: Morning moderate exercise acutely lowers glucose levels in people with type 2 diabetes being prescribed metformin. This difference appears to be driven by individuals that consumed metformin prior to breakfast rather than after breakfast. Morning exercise combined with pre-breakfast metformin persistently reduced glucose compared to morning exercise combined with post-breakfast metformin through the final week (week 6) of the intervention. Our study suggests it may be possible to make simple changes to the time that people with type 2 diabetes take metformin and perform exercise to improve their blood glucose.

A deep-learning model for intracranial aneurysm detection on CT angiography images in China: a stepwise, multicentre, early-stage clinical validation study

Artificial intelligence (AI) models in real-world implementation are scarce. Our study aimed to develop a CT angiography (CTA)-based AI model for intracranial aneurysm detection, assess how it helps clinicians improve diagnostic performance, and validate its application in real-world clinical implementation. We developed a deep-learning model using 16 546 head and neck CTA examination images from 14 517 patients at eight Chinese hospitals. Using an adapted, stepwise implementation and evaluation, 120 certified clinicians from 15 geographically different hospitals were recruited. Initially, the AI model was externally validated with images of 900 digital subtraction angiography-verified CTA cases (examinations) and compared with the performance of 24 clinicians who each viewed 300 of these cases (stage 1). Next, as a further external validation a multi-reader multi-case study enrolled 48 clinicians to individually review 298 digital subtraction angiography-verified CTA cases (stage 2). The clinicians reviewed each CTA examination twice (ie, with and without the AI model), separated by a 4-week washout period. Then, a randomised open-label comparison study enrolled 48 clinicians to assess the acceptance and performance of this AI model (stage 3). Finally, the model was prospectively deployed and validated in 1562 real-world clinical CTA cases. The AI model in the internal dataset achieved a patient-level diagnostic sensitivity of 0·957 (95% CI 0·939-0·971) and a higher patient-level diagnostic sensitivity than clinicians (0·943 [0·921-0·961] vs 0·658 [0·644-0·672]; p<0·0001) in the external dataset. In the multi-reader multi-case study, the AI-assisted strategy improved clinicians' diagnostic performance both on a per-patient basis (the area under the receiver operating characteristic curves [AUCs]; 0·795 [0·761-0·830] without AI vs 0·878 [0·850-0·906] with AI; p<0·0001) and a per-aneurysm basis (the area under the weighted alternative free-response receiver operating characteristic curves; 0·765 [0·732-0·799] vs 0·865 [0·839-0·891]; p<0·0001). Reading time decreased with the aid of the AI model (87·5 s vs 82·7 s, p<0·0001). In the randomised open-label comparison study, clinicians in the AI-assisted group had a high acceptance of the AI model (92·6% adoption rate), and a higher AUC when compared with the control group (0·858 [95% CI 0·850-0·866] vs 0·789 [0·780-0·799]; p<0·0001). In the prospective study, the AI model had a 0·51% (8/1570) error rate due to poor-quality CTA images and recognition failure. The model had a high negative predictive value of 0·998 (0·994-1·000) and significantly improved the diagnostic performance of clinicians; AUC improved from 0·787 (95% CI 0·766-0·808) to 0·909 (0·894-0·923; p<0·0001) and patient-level sensitivity improved from 0·590 (0·511-0·666) to 0·825 (0·759-0·880; p<0·0001). This AI model demonstrated strong clinical potential for intracranial aneurysm detection with improved clinician diagnostic performance, high acceptance, and practical implementation in real-world clinical cases. National Natural Science Foundation of China. For the Chinese translation of the abstract see Supplementary Materials section.

Efficacy and Safety of Cannabidiol Oil on Chronic Insomnia: The First Randomized, Double-Blind, Placebo-Controlled, Crossover, Pilot Study in Thailand

Objective: Cannabidiol (CBD) is a non-intoxicating extract from Cannabis sativa. The advantages of CBD on sleep-wake cycle and insomnia remain sparse. The present study investigated the impact of a continuous four-week sublingual CBD intake on sleep indicators. Materials and Methods: The present study was a randomized, double-blind, placebo-controlled, crossover pilot study involving 45 chronic insomnia patients. The participants were administered medium-chain triglycerides oil soluble cannabidiol (MCT-CBD) using 1 mg/kg/dose, sublingually for four weeks, then two weeks of washout period, and a subsequent four-week placebo phase. Sleep architecture with N1, N2, N3, and rapid eye movement (REM), sleep quality (PSQI), daytime sleepiness (ESS), and quality of life were investigated. Results: Polysomnography (PSG) revealed that the total sleep time (TST), sleep onset latency (SOL), wake time after sleep onset (WASO), and arousal index were significantly improved compared to the patients who were taking placebo, while sleep structure remained unaltered. Additionally, actigraphy showed a substantial improvement in TST, sleep efficiency (SE), and SOL. The results of PSQI, ESS, and EQ-5D-5L were statistically significant and better than placebo (p&lt;0.05). Conclusion: Continuously sublingual CBD treatment could improve sleep duration, sleep maintenance, sleep induction, quality of life, and daytime sleepiness without altering the sleep architecture in patients with chronic insomnia. No evidence of serious side-effects was found. Keywords: Hemp; CBD; Cannabidiol; Cannabis; Insomnia; Sleep

Effect of levodopa on pathological gait in Dravet syndrome: A randomized crossover trial using three-dimensional gait analysis.

Individuals with Dravet syndrome (DS) exhibit progressive gait disturbance. No quantitative studies have been conducted to evaluate the effectiveness of medication for gait disturbance. Therefore, the aim of this study was to evaluate the effectiveness of levodopa for pathological gait in people with DS using three-dimensional gait analysis (3DGA). Nine individuals with DS, ages 6-20 years, participated in a crossover study of levodopa and were randomly assigned to the levodopa precedence or no levodopa precedence group. Levodopa/carbidopa hydrate was prescribed at a dose of 5 mg/kg/day (body weight <60 kg) or 300 mg/day (body weight ≥60 kg). The medication was taken for 4-6 weeks (4-week washout period). 3DGA was performed three times before the study, with and without levodopa. A mixed-effects model was used to evaluate the effectiveness of levodopa. The primary outcome was the change in the Gait Deviation Index (GDI). In addition, spatiotemporal gait parameters, 6-minute walking distance (6MD), and balance were evaluated. The correlation between the effectiveness of levodopa and age or gait performance before starting levodopa was analyzed. Levodopa improved the GDI by 4.2 points, (p = .029), 6MD by 52 m (p = .002), and balance test result by 4.1 mm (p = .011) in participants with DS. No severe adverse events were observed, with the exception of one participant, who exhibited fever and consequently stopped taking levodopa. Levodopa was more effective in younger participants with a higher baseline gait performance. Our randomized crossover trial showed that levodopa has the potential to improve gait disturbance in people with DS.

Comparison of the effects of different functional exercise sequences on lymphedema in breast cancer: protocol for an exploratory randomised controlled cross-over trial

IntroductionBreast cancer-related lymphedema (BCRL) is a common postoperative complication of breast cancer. It develops in a chronic and vicious cycle. Once lymphedema occurs, it cannot be cured and bring serious...

Comparison of two 3D reconstruction models for understanding of complicated female pelvic tumors.

Three-dimensional (3D) reconstructed models have been shown to improve visualization in complex female pelvic tumors. Cinematic rendering (CR) is a 3D imaging technique for computed tomography (CT) images, which creates more realistic images with the ability to enhance imaging of anatomical features for diagnosis. This study was set up to compare two types of 3D models and to validate the use of 3D anatomical techniques for the diagnosis of complex female pelvic tumors. The preclinical, randomized, two-sequence crossover investigation was performed from December 2022 to January 2023 at First Affiliated Hospital of Chongqing Medical University. Sixteen residents and 10 attending surgeons assessed the cases of 23 patients with two types of 3D model images. The surgeons were randomly assigned to two assessment sequences (CR-3D model group and CT-3D model group). For each case, participants selected one question that probed fundamental questions about the tumor's genesis throughout each assessment period. Following a 4-week washout period, case assessments were transferred to the other image modality. The main result assessment was the accuracy of the answers. The time to answer the questions and the case assessment questionnaire was added as a secondary outcome. The mean scores in the CR-3D models (19.35 ± 1.87) varied significantly from those in the CT-CR group (16.77 ± 1.8) (P < 0.001), and solving the questions in the CT-3D model sequence (41.96 ± 6.31 s) varied significantly from that in the CR-3D model sequence (52.88 ± 5.95 s) (P < 0.001). Subgroup analysis revealed that there were statistically significant variations in the scores of female reproductive tumors, pelvic tumors other than the reproductive system, and retroperitoneal tumors (P = 0.005). Analysis of the assessment questionnaire showed that more surgeons choose CR 3D reconstruction (8.31 ± 0.76 vs 7.15 ± 1.19, P < 0.001). The results suggest that each 3D reconstruction method has its own advantages. Surgeons feel that CR reconstruction models are a useful technique that can improve their comprehension of complex pelvic tumors, while traditional 3D models have an advantage in terms of speed to diagnosis.

UPDATE trial: investigating the effects of ultra-processed versus minimally processed diets following UK dietary guidance on health outcomes: a protocol for an 8-week community-based cross-over randomised controlled trial in people with overweight or obesity, followed by a 6-month behavioural intervention

IntroductionObesity increases the risk of morbidity and mortality. A major driver has been the increased availability of ultra-processed food (UPF), now the main UK dietary energy source. The UK Eatwell...

Accuracy of cone-beam breast computed tomography for assessing breast cancer tumor size-comparison with breast magnetic resonance imaging.

Accurate preoperative assessment of tumor size is important in developing a surgical plan for breast cancer. The purpose of this study was to evaluate the accuracy of cone-beam breast computed tomography (CBBCT) and magnetic resonance imaging (MRI) in the assessment of tumor size and to analyze the factors influencing the discordance. In this retrospective study, patients with breast cancer who underwent preoperative contrast-enhanced CBBCT (CE-CBBCT) and dynamic contrast-enhanced MRI (DCE-MRI) and received a complete pathologic diagnosis from August 2020 to December 2021 were included, using the pathological result as the gold standard. Two radiologists assessed the CBBCT and MRI features and measured the tumor size with a 2-week washout period. Intraclass correlation coefficient (ICC) and Bland-Altman analyses were used to assess inter-observer reproducibility and agreement based on CBBCT, MRI and pathology. Univariate analyses of differences in clinical, pathological and CBBCT/MRI features between the concordant and discordant groups was performed using the t-test, Mann-Whitney U-test, Chi-squared test and Fisher's exact test. Multivariate analyses were used to identify factors associated with discordance of CBBCT/MRI with pathology. A total of 115 female breast cancer patients (115 lesions) were included. All patients had a single malignant tumor of the unilateral breast. The reproducibility and the agreement ranged from moderate to excellent (ICC =0.607-0.983). Receiver operating characteristic (ROC) analyses showed that the cut-off values of CBBCT-pathology and MRI-pathology discordance were 2.25 and 2.65 cm, respectively. CBBCT/MRI-pathology concordance was significantly associated with the extent of pathology, lesion type, presence of calcification, human epidermal growth factor receptor 2 (HER2) status and fatty infiltration (P<0.05). In lesions containing calcification, the difference of CBBCT-pathology was significantly smaller than MRI-pathology (P=0.021). Non-mass enhancement (NME) was the main predictor of CBBCT- or MRI-pathology discordance [odds ratio (OR) =3.293-6.469, P<0.05], and HER2 positivity was a predictor of CBBCT-pathology discordance (OR =3.514, P=0.019). CBBCT and MRI have comparable accuracy in measurement of tumor size, and CBBCT is advantageous in assessing the size of calcified lesions. NME and HER2 positivity are significant predictors of CBBCT-pathology discordance. This suggests that CBBCT might serve as an alternative imaging technique to assess tumor size when patients do not tolerate MRI.

Effects of sodium-glucose co-transporter 2 inhibitors on ultrafiltration in patients with peritoneal dialysis: a protocol for a randomized, double-blind, placebo-controlled, crossover trial (EMPOWERED)

BackgroundVolume overload is common and associated with high mortality in patients on peritoneal dialysis (PD). Traditional strategies including diuretics, water/salt restriction, and icodextrin-based solutions cannot always fully correct this condition, necessitating novel alternative strategies. Recent studies confirmed the expression of sodium–glucose cotransporter 2 (SGLT2) in the human peritoneum. Experimental data suggest that SGLT2 inhibitors decrease glucose absorption from the PD solution, thereby increasing the ultrafiltration volume. This trial aims to assess whether SGLT2 inhibitors increase the ultrafiltration volume in patients on PD.MethodsThe EMPOWERED trial (trial registration: jRCTs051230081) is a multicenter, randomized, double-blind, placebo-controlled, crossover trial. Patients with clinically diagnosed chronic heart failure are eligible regardless of the presence of diabetes if they use at least 3 L/day glucose-based PD solutions. Participants will be randomly assigned (1:1) to receive empagliflozin 10 mg once daily and then placebo or vice versa. Each treatment period will last 8 weeks with a 4-week washout period. This study will recruit at least 36 randomized participants. The primary endpoint is the change in the daily ultrafiltration volume from baseline to week 8 in each intervention period. The key secondary endpoints include changes in the biomarkers of drained PD solutions, renal residual function, and anemia-related parameters.ConclusionsThis trial aims to assess the benefit of SGLT2 inhibitors in fluid management with a novel mechanism of action in patients on PD. It will also provide insights into the effects of SGLT2 inhibitors on solute transport across the peritoneal membrane and residual renal function.

Efficacy of a novel dentifrice containing bioactive glass-ceramic for dentinal hypersensitivity: A double-blind randomized controlled trial in Chinese adults

ObjectiveTo assess the efficacy and safety of a toothpaste containing 7.5 % HX-BGC in combating dentinal hypersensitivity. MethodsA single-center, randomized, double-blind, three-group parallel-controlled design was employed, with Schiff Index and Yeaple Index as measurement indicators. The study evaluated the effectiveness of HX-BGC toothpaste, NovaMin toothpaste, and a negative control toothpaste without desensitizing agents. Eligible subjects underwent baseline examination after a 2-week washout period, and those meeting inclusion criteria and not meeting exclusion criteria entered the study. Participants were randomly assigned to use one of the three toothpastes. Follow-up examinations were conducted immediately after a single use and at 2, 4, and 6 weeks. Intra-group and inter-group comparisons were made for Schiff and Yeaple indices. Safety of the experimental toothpastes was assessed through participant feedbacks and oral soft tissue examinations. ResultsSubjects in the three groups were balanced in terms of age and gender distribution, with no baseline differences in indicators. Immediately after a single application of toothpaste, Yeaple indices increased, and Schiff indices decreased, with no significant differences among the groups. After 2 weeks of continuous use, Yeaple indices increased in all groups, with significant differences observed between the HX-BGC group and the other two groups. Schiff indices decreased in all groups, with the NovaMin group showing significant differences compared to the negative control group. At weeks 4 and 6, both indices in the HX-BGC group and the NovaMin group were significantly better than those in the negative control group, with the HX-BGC group outperforming the NovaMin group in the Yeaple index. No serious adverse reactions related to the study products were observed or reported by any participants. Clinical SignificanceThis clinical trial confirmed the efficacy of HX-BGC in anti-dentinal hypersensitivity and supported the clinical application of the dentifrice containing HX-BGC. ConclusionCompared to the negative control group, both HX-BGC and NovaMin toothpaste groups demonstrated more significant effects in combating dentinal hypersensitivity. No adverse reactions related to the experimental toothpastes were observed.

Oral mirtazapine decreases the gastrointestinal adverse effects in cats on doxorubicin chemotherapy

Anorexia, depression, and vomiting are the common adverse effects of chemotherapy in humans and animals. Mirtazapine is primarily used as an appetite stimulant and antiemetic in dogs and cats. Therefore, we evaluated the efficacy of mirtazapine in reducing the gastrointestinal adverse effects in cats receiving doxorubicin chemotherapy. This single-masked, placebo-controlled crossover study enrolled 11 cats with malignant mammary gland tumors. The cats were randomly assigned to receive either mirtazapine (1.88 mg/cat) or placebo every 48 h for 2 weeks from the first initiation of doxorubicin chemotherapy. Each cat was then crossed over to the alternate group on the subsequent chemotherapy with a 1-week wash-out period. The owners were asked to record appetite score, activity score, episodes of vomiting and diarrhea for 2 weeks after each doxorubicin administration. Cats treated with mirtazapine showed significantly increased bodyweight compared with those on placebo (P = 0.010). The appetite and activity scores during mirtazapine treatment was significantly higher than those during placebo treatment (P = 0.005 and 0.018, respectively). Furthermore, the prevalence of episodes of vomiting during mirtazapine treatment was significantly lower than that during placebo treatment (P = 0.026). Our results demonstrate that mirtazapine can significantly increase bodyweight, appetite, and activity and reduce vomiting in cats after doxorubicin chemotherapy.

Deep-learning for automated detection of MSU deposits on DECT: evaluating impact on efficiency and reader confidence.

Dual-energy CT (DECT) is a non-invasive way to determine the presence of monosodium urate (MSU) crystals in the workup of gout. Color-coding distinguishes MSU from calcium following material decomposition and post-processing. Manually identifying these foci (most commonly labeled green) is tedious, and an automated detection system could streamline the process. This study aims to evaluate the impact of a deep-learning (DL) algorithm developed for detecting green pixelations on DECT on reader time, accuracy, and confidence. We collected a sample of positive and negative DECTs, reviewed twice-once with and once without the DL tool-with a 2-week washout period. An attending musculoskeletal radiologist and a fellow separately reviewed the cases, simulating clinical workflow. Metrics such as time taken, confidence in diagnosis, and the tool's helpfulness were recorded and statistically analyzed. We included thirty DECTs from different patients. The DL tool significantly reduced the reading time for the trainee radiologist (p = 0.02), but not for the attending radiologist (p = 0.15). Diagnostic confidence remained unchanged for both (p = 0.45). However, the DL model identified tiny MSU deposits that led to a change in diagnosis in two cases for the in-training radiologist and one case for the attending radiologist. In 3/3 of these cases, the diagnosis was correct when using DL. The implementation of the developed DL model slightly reduced reading time for our less experienced reader and led to improved diagnostic accuracy. There was no statistically significant difference in diagnostic confidence when studies were interpreted without and with the DL model.

Effect of amlodipine on the circulating renin-angiotensin-aldosterone system in healthy cats.

Systemic hypertension (SH) is a common cardiovascular disease in older cats that is treated primarily with the calcium channel blocker amlodipine besylate (AML). The systemic effect of AML on the classical and alterative arms of the renin-angiotensin-aldosterone system (RAAS) in cats is incompletely characterized. To determine the effect of AML compared to placebo on circulating RAAS biomarkers in healthy cats using RAAS fingerprinting. Twenty healthy client-owned cats. Cats were administered amlodipine besylate (0.625 mg in toto) or placebo by mouth once daily for 14 days in a crossover design with a 4-week washout period. Plasma AML concentrations and RAAS biomarker concentrations were measured at multiple timepoints after the final dose in each treatment period. Time-weighted averages for RAAS biomarkers over 24 hours after dosing were compared between treatment groups using Wilcoxon rank-sum testing. Compared to placebo, AML treatment was associated with increases in markers of plasma renin concentration (median 44% increase; interquartile range [IQR] 19%-86%; P = .009), angiotensin I (59% increase; IQR 27-101%; P = .006), angiotensin II (56% increase; IQR 5-70%; P = .023), angiotensin IV (42% increase; -19% to 89%; P = .013); and angiotensin 1-7 (38% increase; IQR 9-118%; P = .015). In healthy cats, administration of AML resulted in nonspecific activation of both classical and alternative RAAS pathways.

Effect of Hemodialysis with Medium Cut-Off versus High-Flux Membranes on Endothelial Function of Patients with Chronic Kidney Disease

Introduction: Endothelial dysfunction (ED) is considered a marker of vascular complications, especially in patients with end-stage kidney disease (ESKD). Inflammation and the uremic state contribute to ED in patients undergoing hemodialysis (HD). Recently, the medium cut-off (MCO) dialysis membrane has been proposed to efficiently remove inflammatory cytokines and large, middle-sized uremic toxins, with the potential effect to improve endothelial function. This study aimed to compare the effect of dialysis with MCO or high-flux membranes on the endothelial function of patients on chronic HD. Methods: A prospective, randomized, crossover study in which 32 patients with ESKD were dialyzed for 12 weeks with each membrane, including a 4-week washout period between treatments. Endothelial function was assessed by flow-mediated dilation (FMD) using brachial artery ultrasound at weeks 1, 12, 16, and 28. Results: The population consisted of 59% men, 52.7 ± 13.4 years, 16% non-black, on HD for 8.8 (4.1–15.1) years, and 72% with arteriovenous fistula. Hypertension was the most common etiology of chronic kidney disease, and 34% of patients had previous cardiovascular disease. Patients were grouped, regardless of treatment sequence, into MCO or high-flux groups, since no carryover (p = 0.634) or sequence (p = 0.998) effects were observed in the FMD assessment. The ANOVA model with repeated measures showed no effects of treatment (p = 0.426), time (p = 0.972), or interaction (p = 0.413) in the comparison of FMD between the MCO and high-flux groups. Conclusion: Dialysis performed with MCO, or high-flux membranes, had no influence on endothelial function in patients undergoing HD. However, a trend towards increased FMD was observed with the use of the MCO membrane.