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OBJECTIVE: Health literacy is a critical health determinant, for which few computerized, self-administered assessments exist. This study adapted and tested the reliability of the Newest Vital Sign© (NVS) as a computerized, self-administered health literacy screener. METHODS: Phase one involved 33 participants to create response options for a computerized, self-administered NVS (C-NVS). Phase two was a randomized crossover trial to test the consistency of C-NVS and original, interviewer-administered NVS (I-NVS) scores in 89 participants. RESULTS: Linear mixed-effects regression model results showed a significant carryover effect (p

The evidence on the impact of fruits and vegetable types on cardiovascular risk factors remains limited. Specifically, the utilisation of biomarkers to objectively measure dietary compliance and metabolic responses is emerging. This protocol and baseline characteristics of a pilot randomised controlled, crossover, dietary intervention study aimed to examine the effects of citrus fruits, cruciferous vegetables, or common fruits and vegetables on cardiovascular risk factors. A total of 39 volunteers with untreated prehypertension was recruited and consumed a standardised, provided diet with eight daily portions of citrus fruits and cruciferous vegetables, common fruits and vegetables, or a low fruit and vegetable diet (two portions/d, control diet) in a random order for 2 weeks each, separated by a wash-out week. A targeted cohort-based recruitment strategy was utilised and resulted in 74% of participants recruited by re-contacting preselected individuals from two cohort studies with a 15% average enrolment rate. Participants had an average age of 54.4 years (±6.1 years), BMI of 27.9 kg/m2, and BP of 135/81 mmHg and were mainly male (67%). The primary outcome was office blood pressure; secondary outcomes included arterial stiffness, lipid profiles, inflammation, cognitive function, and subjective mood. Biofluids, i.e., 24 h urine, stool, and blood samples, were collected for biomarker measurements with multiple metabolomic platforms and the gut microbial composition, together with traditional dietary biomarkers. [ABSTRACT FROM AUTHOR]

Summary Many patients with depression report insomnia symptoms that profoundly affect their health and well‐being. Non‐pharmacological treatments of insomnia may be preferable for some patients. In this randomised crossover trial, we investigated the efficacy of the Protac Ball Blanket® on insomnia among patients with depression. Included patients (n = 45) were diagnosed with unipolar depression, and with subjective insomnia and poor sleep quality (Pittsburgh Sleep Quality Index Score > 5). Each patient slept 2 weeks with a Protac Ball Blanket® and 2 weeks with a control duvet. Randomisation defined the order of the 2‐week sleep periods. Patients served as their own control in this design. The primary outcome was changes in total night‐time sleep. Secondary outcomes were sleep‐onset latency, number of awakenings, wake after sleep onset, daily use of pro necessitate sedatives and hypnotics, subjective sleep quality (Pittsburgh Sleep Quality Index), insomnia severity (Insomnia Severity Index), symptoms of depression (Hamilton Depression Rating Scale, Major Depression Inventory), symptoms of anxiety (Beck Anxiety Index), and patient‐reported outcomes concerning interpersonal sensitivity, neurasthenia, anxiety and depression (Self‐Reported Symptom State Scale). Paired two‐sided t‐tests were used to compare the means of the differences of the outcomes. Protac Ball Blanket® increased total night‐time sleep by 12.9 min (95% confidence interval: 1.21–24.63, p = 0.031). Among the secondary outcomes, Protac Ball Blanket® decreased Hamilton Depression Rating Scale by 2.78 (95% confidence interval: −5.44; −0.11, p = 0.042) and Insomnia Severity Index by 2.98 (95% confidence interval: −5.45; −0.50, p = 0.020). No changes were observed in sleep‐onset latency, number of awakenings, wake after sleep onset, Pittsburgh Sleep Quality Index, Major Depression Inventory, Beck Anxiety Index, Self‐Reported Symptom State Scale, and medication use. The results suggest that some patients may benefit from Protac Ball Blanket® as an add‐on non‐pharmacological treatment to improve sleep in depression. [ABSTRACT FROM AUTHOR]

Kale (Brassica oleracea species) is considered a functional food whose macronutrient and phytochemical contents are considered beneficial and widely considered as a superfood. In the present 6-week cross-over trial with a 2-week washout period, we compared the beneficial effects of freeze-dried kale over peas among Arab women with obesity. A total of 124 Saudi women with obesity were allocated to receive either freeze-dried kale (n = 62) or freeze-dried peas (n = 62) given in the form of 3-gram sachets thrice daily for 2 weeks, followed by a 2-week washout period and a cross-over of 4 weeks. Anthropometric measurements, glucose, lipids and markers of gut barrier function were assessed at baseline and post-intervention. Participants who took kale supplementation first resulted in significant weight reduction (p = 0.02) which was not observed among those who took peas first. Participants receiving pea supplementation first experienced a significant decline in Hba1c (p = 0.005) and CD14 (p = 0.03), but C-peptide increased (p = 0.05). Crossover analysis revealed significant carryover effects in most variables with non-significant combined treatment effects. Among the variables with no carryover effect with significant combined treatment effect include HbA1c which was in favor of the pea group (p = 0.005) and C-peptide which was modestly in favor of the kale group (p = 0.05). While both freeze dried kale and pea supplementation appear beneficial, supplementation of freeze-dried pea appears to be more effective in terms of acute glycemic control than kale. The study suggests that common but less-hyped vegetables such as pea maybe equally, if not more beneficial than the more expensive promoted superfoods such as kale. Longer clinical trials using a parallel design instead of cross-over are recommended to strengthen present findings.

Objective: Health literacy is a critical health determinant, for which few computerized, self-administered assessments exist. This study adapted and tested the reliability of the Newest Vital Sign© (NVS) as a computerized, self-administered health literacy screener. Methods: Phase one involved 33 participants to create response options for a computerized, self-administered NVS (C-NVS). Phase two was a randomized crossover trial to test the consistency of C-NVS and original, interviewer-administered NVS (I-NVS) scores in 89 participants. Results: Linear mixed-effects regression model results showed a significant carryover effect (p

To compare efficacy of continuous positive airway pressure (CPAP) and oral appliance (OA) in management of various grades of obstructive sleep apnea (OSA). Thirty polysomnography diagnosed cases of OSA were divided into three groups based on baseline apnea hypopnea index (AHI) as follows: group 1: mild OSA (AHI = 5-14.9), group 2: moderate OSA (AHI = 15-29.9), and group 3: severe OSA (AHI >30) with 10 patients in each group. Half of the patients in each group were randomly allocated to CPAP or OA therapy, and crossover of therapy was performed after two months. AHI, Epworth's Sleepiness Scale (ESS), and mean oxygen saturation (SPO2) were measured at baseline, after each arm of treatment and after the crossover. A questionnaire survey including information regarding pretreatment sleep symptoms and improvement after therapy was performed at above time frames. At the end of therapy, the patients were surveyed regarding satisfaction and perceived effectiveness with both modalities. CPAP was more efficacious in reducing AHI and SPO2 as compared with OA across the three study groups. The improvement in most sleep-related symptoms was higher with CPAP. The satisfaction and perception on effectiveness of treatment were higher with OA than CPAP across three study groups (P-value<0.05 for all). OA is an effective alternative to CPAP across all grades of OSA in selected cases, which is more preferred owing to higher effectiveness and satisfaction among the patients. [ABSTRACT FROM AUTHOR]

Objective: Dementia affects individuals older than 65 years. Currently, residential aged care facilities (RACF) use psychotropic medications to manage behavioural and neuropsychiatric symptoms of dementia (BPSD), which are recommended for short‐term use and have substantial side effects, including increased mortality. Cannabinoid‐based medicines (CBM) have some benefits that inhibit BPSD and cause minimal adverse effects (AEs), yet limited research has been considered with this population. The study aimed to determine a tolerable CBM dose (3:2 delta‐9‐tetrahydrocannabinol:cannabidiol), and assessed its effect on BPSD, quality of life (QoL) and perceived pain. Methods: An 18‐week randomised, double‐blinded, crossover trial was conducted. Four surveys, collected on seven occasions, were used to measure changes in BPSD, QoL and pain. Qualitative data helped to understand attitudes towards CBM. General linear mixed models were used in the analysis, and the qualitative data were synthesised. Results: Twenty‐one participants (77% female participants, mean age 85) took part in the trial. No significant differences were seen between the placebo and CBM for behaviour, QOL or pain, except a decrease in agitation at the end of treatment in favour of CBM. The qualitative findings suggested improved relaxation and sleep among some individuals. Post hoc estimates on the data collected suggested that 50 cases would draw stronger conclusions on the Neuropsychiatric Inventory. Conclusions: The study design was robust, rigorous and informed by RACF. The medication appeared safe, with minimal AEs experienced with CBM. Further studies incorporating larger samples when considering CBM would allow researchers to investigate the sensitivity of detecting BPSD changes within the complexity of the disease and concomitant with medications. [ABSTRACT FROM AUTHOR]

In clinical trials, crossover design is widely used to assess treatment effects of drugs. Due to many practical issues, each patient in the study may receive only a subset of treatments under comparison, which is called an incomplete block crossover design. Correspondingly, the associated challenges are limited information and small sample size. In this article, we propose a Bayesian approach to analyze the incomplete block crossover design. Markov chain sampling method is used to analyze the model. We use several approaches such as data augmentation, scaled mixture of normals representation, parameter expansion to improve efficiency. The approach is illustrated using a simulation study and a real data example. [ABSTRACT FROM AUTHOR]

Some studies have directly compared the National Acoustic Laboratories' prescription for non-linear hearing aids (HAs) version 2 (NAL-NL2) and Desired Sensation Level for non-linear HAs version 5 (DSLv5), although none were performed in Japan. As the Japanese language is a tonal language that has different linguistic characteristics than those of the studied languages, we compared the outcomes of the NAL-NL2 and DSLv5 in hearing-impaired Japanese participants. A crossover-controlled trial was conducted on 18 first-time HA users with bilateral moderate sensorineural hearing loss. Participants wore HAs adjusted with each prescriptive method for four weeks. The prescriptions were assessed using speech discrimination testing and the abbreviated profile of hearing aid benefit (APHAB). Consequently, participants were asked to select their preferred prescription and determine which was better for "listening to a conversation" and when "noisy." The mean DSLv5 real ear insertion gain for an input level of 65 dB sound pressure level (SPL) was higher than that of the NAL-NL2 at 250 and 500 Hz. The average speech discrimination score was 78 ± 14% at a 65-dB SPL and 75 ± 17% at an 80-dB SPL for the NAL-NL2, and 79 ± 11% at a 65-dB SPL and 77 ± 17% at an 80-dB SPL for the DSLv5. These differences were not significant. No significant differences were observed in APHAB subscale scores between the two prescription methods. Ultimately, 11 (61%) and 7 (39%) participants preferred the NAL-NL2 and DSLv5, respectively, with no significant differences. Although the gain of the NAL-NL2 is smaller than that of the DSLv5, both had the same hearing effect. Therefore, the NAL-NL2 may be more useful than the DSLv5 in Japanese. [ABSTRACT FROM AUTHOR]

The patient–physician relationship is a critical determinant of patient health outcomes. Verbal and non-verbal communication, such as eye gaze, are vital aspects of this bond. Neurobiological studies indicate that oxytocin may serve as a link between increased eye gaze and social bonding. Therefore, oxytocin signaling could serve as a key factor influencing eye gaze as well as the patient–physician relationsh ip. We aimed to test the effects of oxytocin on gaze to the eyes of the physician and the patient–physician relationship by conducting a randomized placebo-controlled crossover trial in healthy volunteers with intranasally administered oxytocin (with a prev iously effective single dose of 24 IU, EudraCT number 2018-004081-34). The eye gaze of 68 male volunteers was studied using eye tracking during a simulated video call consultation with a physician, who provided information about vaccination against the human papillomavirus. Relationship outcomes, including trust, satisfaction, and perceived physician communication style, were measured using questionnaires and corrected for possible confounds (social anxiety and attachment orientation). Additional secondary outcome measures for the effect of oxytocin were recall of information and pupil diameter and exploratory outcomes included mood and anxiety measures. Oxytocin did not affect the eye-tracking p arameters of volunteers’ gaze toward the eyes of the physician. Moreover, oxytocin did n ot affect the parameters of bonding between volunteers and the physician nor other secondary and exploratory outcomes in this setting. Bayesian hypothesis testing provided evidence for the absence of effects. These results contradict the notion that oxy tocin affects eye gaze patterns or bonding.

Background The aim was to investigate and challenge the belief that swimming immediately after eating is dangerous and also to investigate what potentially could happen when swimming immediately after a meal. We wanted to explore feasibility and get background data to perform sample size calculations and choose outcome parameters for a full-scale randomized trial. Methods The trial was performed during lunch breaks at a medical writing course in Turkey in June 2022. Participants were randomised on the first trial day to swim 14 meters breaststroke immediately after lunch or wait 30 minutes after eating, with crossover on the second trial day. Main outcomes measures were mortality, and mood, discomfort, and adverse events were assessed in participant-reported questionnaires. Participants completed a Profile of Mood States-Adolescents questionnaire, a visual analogue scale for discomfort, and a questionnaire of adverse events after each swim. Results A total of 26 participants completed the trial. No cases of mortality, drowning, resuscitation, side stitch, or muscle cramps were reported. The participants reported no significant difference in their mood states after each swim and no significant difference was found regarding the participants’ swimming time (P = 0.53). However, more discomfort was reported when swimming immediately instead of 30 minutes after eating (P = 0.05). Conclusions It seems that swimming after eating is safe since no mortality or cramps were registered. However, a significant level of discomfort was found when swimming immediately after eating lunch. This feasibility trial provides background data for a future full-scale randomised trial. Clinicaltrials.gov registration NCT05401396 (25/05/2022).

BackgroundN95 respirators are used to limit the transmission of respiratory viruses in clinical settings. There are two to three major types of N95 available for all healthcare workers in Hong Kong. However, after the coronavirus outbreak and the consequent shortage of many commonly used respirators, several new N95 respirators were adopted temporarily in clinical settings without evaluation. Prior literature indicates that traditional N95 respirators used in hospitals in Hong Kong are not fit for Chinese people and have fit rates ranging from 50 to 60%. This study aims to investigate and compare the fit rate, real-time leakage, and mask usability of traditional and new N95 respirators among Chinese healthcare workers.MethodsThis study will employ two sequential phases. Phase 1 has a cross-sectional exploratory design used to investigate the fit rate and mask usability of three types of respirators. Phase 2 will examine the effectiveness of respiratory protection by comparing traditional and new N95 respirators by a randomized crossover trial. Eligible participants will be randomly allocated through a controlled crossover experiment to either a traditional or new respirator group (n = 100 in each arm) for performing standard clinical procedures. The primary outcome (real-time leakage) will be recorded at 30 s intervals during nasopharyngeal suctioning and cardiopulmonary resuscitation. The secondary outcomes are the fit rate and mask usability. After a 2 min suctioning (15 s twice) and 4 min one-person CPR, the fit rate (assessed by standard N95 fit testing) and mask usability (measured by self-reported mask usability scale) will be recorded as data of post-procedure. After 10 min rest, measurement of real-time leakage (i.e., crossover), fit test, and usability will be repeated.DiscussionThe result of real-time leakage will be a vital indicator of the respiratory protection of Chinese healthcare workers while performing prevalent clinical procedures, such as resuscitation. The fit rate and usability result will serve as an essential reference for consumable purchase policy in clinical settings.Trial registration: ISRCTN registry: ISRCTN40115047. Retrospectively registered on May 9, 2023. https://www.isrctn.com/ISRCTN40115047.

BackgroundThe intestinal microbiome is an appealing target for interventions in ESKD because of its likely contribution to uremic toxicity. Before conducting clinical trials of microbiome-altering treatments, it is necessary to understand the within-person and between-person variability in the composition and function of the gut microbiome in patients with ESKD.MethodsWe conducted a multicenter, nonrandomized, crossover feasibility study of patients on maintenance hemodialysis consisting of three phases: pretreatment (8 weeks); treatment, during which the prebiotic, p-inulin, was administered at a dosage of 8 g twice daily (12 weeks); and post-treatment (8 weeks). Stool samples were collected 1-2 times per week and blood was collected weekly for 28 weeks. The gut microbiome was characterized using 16S ribosomal-RNA sequencing and metabolomic profiling.ResultsA total of 11 of the 13 participants completed the 28-week study. Interparticipant variability was greater than intraparticipant variability for microbiome composition (P

Adherence is a critical factor to consider when interpreting study results from randomized clinical trials (RCTs) comparing one diet to another, but it is frequently not reported by researchers. The purpose of this secondary analysis of the Keto-Med randomized trial was to provide a detailed examination and comparison of the adherence to the two study diets (Well Formulated Ketogenic Diet (WFKD) and Mediterranean Plus (Med-Plus)) under the two conditions: all food being provided (delivered) and all food being obtained by individual participants (self-provided). Diet was assessed at six time points including baseline (×1), week 4 of each phase when participants were receiving food deliveries (×2), week 12 of each phase when participants were preparing and providing food on their own (×2), and 12 weeks after participants completed both diet phases and were free to choose their own diet pattern (×1). The adherence scores for WFKD and Med-Plus were developed specifically for this study. Average adherence to the two diet patterns was very similar during both on-study time points of the intervention. Throughout the study, a wide range of adherence was observed among participants-for both diet types and during both the delivery phase and self-provided phase. Insight from this assessment of adherence may aid other researchers when answering the important question of how to improve behavioral adherence during dietary trials. This study is registered at clinicaltrials.gov NCT03810378.

Introduction: We developed a novel rice-based medical food for diabetes (MFDM) powder formula, using locally available ingredients in Thailand, which can potentially improve patient access to diabetes-specific formula (DSF) by reducing cost and improving availability. Purpose: The goals of our studies were to 1) measure the glycemic index (GI) and glycemic load (GL) of the MFDM powder formula in healthy individuals, and 2) assess postprandial glucose, insulin, satiety, hunger, and gastrointestinal (GI) hormone responses in adults with prediabetes or early type 2 diabetes after consuming MFDM in comparison with a commercially available standard formula (SF) and a DSF. Methods: In Study 1, glycemic responses were assessed using the area under the curve (AUC), which was used to calculate GI and GL. Study 2 was a doubleblinded multi-arm randomized crossover trial enrolling participants with either prediabetes or type 2 diabetes of ≤6 years. At each study visit, participants consumed either MFDM, SF, or DSF which contained 25 g of carbohydrates. Hunger and satiety were assessed using a visual analog scale (VAS). Glucose, insulin, and GI hormones were assessed using AUC. Results: All participants tolerated the MFDM well with no adverse events. In Study 1, the measured GI was 39 ± 6 (low GI) and GL was 11 ± 2 (medium GL). In Study 2, glucose and insulin responses were significantly lower after MFDM compared with SF (p-value<0.01 for both), however, those responses were similar between MFDM and DSF. MFDM suppressed hunger, promoted satiety, stimulated active GLP-1, GIP, and PYY, and suppressed active ghrelin although these changes were similar to SF and DSF. Conclusions: MFDM had a low GI and a low-to-medium GL. In people with prediabetes or early type 2 diabetes, MFDM elicited reduced glucose and insulin responses when compared with SF. Rice-based MFDM may be an option for patients who are at risk for postprandial hyperglycemia. [ABSTRACT FROM AUTHOR]

Background: γ-Aminobutyric acid (GABA) is a primary inhibitory neurotransmitter that plays a significant role in the central nervous system. Studies on both animals and humans show that GABA has the pharmacological potential for reducing the impact of cognitive disorders, as well as enhancing cognitive functions and mood. However, its specific effects on human attention and working memory have not yet been extensively studied. Aims: In this randomized, double-blind, placebo-controlled, and crossover trial, we aimed to test whether the administration of 800 mg GABA, dissolved in a drink, acutely affected visual working memory (VWM) maintenance, as well as temporal and spatial attention in healthy adults. Methods: The participants were 32 young adults (16 females and 16 males). Working memory recall precision, spatial attention and temporal attention were measured by a delayed match-to-sample task, a visual search (VS) task and a speeded rapid serial visual presentation task, respectively. Participants completed two experimental sessions (GABA and Placebo) in randomized and counterbalanced order. In each session, 45 min after administration of the drink, they completed all three aforementioned cognitive tasks. Results: Linear mixed model analysis results showed that GABA increased VS time, compared to the placebo, but did not affect VS accuracy, temporal attention, nor VWM precision. Conclusions: The results suggest that GABA increases VS time but does not affect temporal attention and memory, and that previously reported effects on cognition might rely on other functions. [ABSTRACT FROM AUTHOR]

Background: The Integrated Palliative Care Outcome Scale (IPOS) validly and reliably measures symptoms and concerns of those receiving palliative care. Aim: To determine the equivalence of the paper version with an electronic version of the IPOS (eIPOS). Design: Multicentre randomised crossover trial (NCT03879668) with a within-subject comparison of the two modes (washout period 30 min). Setting/Participants: Convenience sample of specialist inpatient and palliative home care patients aged over 18 years with cancer and non-cancer conditions was recruited. Scores were compared using intraclass correlation coefficients (ICC), Bland-Altman plots and via a mixed-effects analysis of variance. Results: Fifty patients were randomised to complete paper-electronic (n = 24) and electronic-paper (n = 26) IPOS with median age 69 years (range 24–95), 56% male, 16% non-cancer. The ICCs showed very high concordance for the total score (ICC 0.99, 95% CI 0.98–1.00), lowest ICCs being observed for symptoms 'Appetite loss' and 'Drowsiness' (ICC 0.95, 95% CI 0.92–0.97). Nine of seventeen items had ICCs above 0.98, as did all subscales. No statistically significant mode, order, age, and interaction effects were observed for IPOS total score and subscales, except for 'Communication' (Fmode = 5.9, p = 0.019). Fifty-eight percent preferred the electronic version. In the group 75+ years, 53% preferred the paper version. Only three entries in the free-text main problems differed between the versions. Conclusion: The very high equivalence in scores and free text between the IPOS and the eIPOS demonstrates that eIPOS is feasible and reliable in an older palliative population. [ABSTRACT FROM AUTHOR]

Objectives Silver fibre gloves transport heat from the palm to the fingers, possibly reducing the burden of RP in SSc patients. We aim to evaluate the clinical efficiency of this intervention. Methods A multicentre, double-blind, randomized trial was performed, accounting for interindividual differences and external factors using a crossover design. Patients were randomized in two groups: group 1 wore 8% silver fibre gloves in period 1 and normal gloves in period 2 and group 2 vice versa. Each period lasted 6 weeks. The primary outcome was the Raynaud Condition Score (RCS) over time (minimal clinical important difference 1.4), assessed three times per week using an online questionnaire. Secondary outcomes included vascular complications and Scleroderma-Health Assessment Questionnaire (SHAQ). Outcomes were evaluated before unblinding using linear mixed models. Results A total of 85 SSc patients were included, with 76 completing the study. The mean RCS during 2 weeks before the study (i.e. without gloves) was 6.4 (s. d. 1.6). Both with silver fibre gloves and normal gloves the mean RCS decreased to 3.9 (s. d. 2.3) with a similar course over time. There was no difference in mean RCS over time between the type of gloves [β = 0.067 (95% CI −0.006, 0.19)]. Of secondary outcomes, total SHAQ [β = 0.036 (95% CI 0.026, 0.046)] was slightly higher with silver fibre gloves, which is clinically irrelevant. Three patients developed new digital ulcers with normal gloves vs one patient with silver fibre gloves [odds ratio 3.2 (95% CI 0.32, 31.1)]. Conclusions Wearing gloves in SSc patients clearly decreases the RP burden. Our results do not support the hypothesis that increased heat transport of 8% silver fibre gloves is associated with less disease burden as measured in this study by the RCS compared with normal gloves. Clinical trial registration number Netherlands Trial register (https://www.trialregister.nl/) NL7904 [ABSTRACT FROM AUTHOR]

Stoma bag filter-related issues, such as ballooning (the bag filling with gas), remain highly prevalent among users. The full-circle filter was purposely designed to reduce ballooning through the inclusion of a unique, full-circle pre-filter. Two similar randomized crossover trials were conducted to compare the performance of the full-circle filter with a dual filter in adults with a colostomy (n = 20) or an ileostomy (n = 20). The frequency of ballooning was significantly lower with the full-circle filter versus the dual filter in participants with a colostomy (p < 0.0007) and in participants with an ileostomy (p < 0.0001). No significant differences were observed in the frequency of other issues (pancaking, odor problems, and ostomy solution discretion) between the filters. On average, participants with an ileostomy wore ostomy solutions with the full-circle filter for 3.3 h longer than ostomy solutions with the dual filter (p < 0.0001); wear-time in users with a colostomy was comparable between the filters. Considering the lack of published research on stoma bag filters and the high prevalence of filter-related issues, these data provide important information for health care practitioners who support people living with a stoma. [ABSTRACT FROM AUTHOR]

Background: Mild cognitive impairment (MCI) is an early stage of cognitive decline in individuals who are still able to perform their activities of daily living. They are at increased risk of developing dementia. Improving and maintaining cognitive functions are essential goals for older people with MCI to delay or prevent the transition to dementia. Objective: This study investigated the effect of the neurobic exercise program on memory performance among community-dwelling older adults with MCI. Methods: A single-blind, randomized, controlled, two-period crossover design was used. Thirty-two older adults who met the study criteria were randomly assigned to one of two sequence groups, A (n =16) and B (n = 16). Group A received three weeks of neurobic exercise, followed by a three-week washout period, and then three weeks of the traditional brain exercise program. Group B received the treatments in the reverse order but otherwise in a similar manner. Two aspects of memory performance were evaluated: subjective memory and objective memory. Blinded evaluators measured the outcomes four times at baseline, post-intervention (week 3), follow-up stage (week 7), and the end of the study (week 9). Descriptive statistics, independent t-tests, and repeated measures ANOVA were employed for data analyses. Results: For subjective memory, rmANOVA revealed a significant difference of within-subject (F1.437, 43.113 = 9.324, p

Abstract Background Venous cannulation is among the most stressful and painful experiences of children hospitalization. Children with thalassemia need regular blood transfusion which needs venous access each time. The quality of care and quality of life of children will be improved if appropriate methods are used to reduce pain. This study aimed to compare vapocoolant spray and music in the reduction of pain of Venous cannulation in children with thalassemia. Methods The study was a randomized controlled clinical trial with a cross-over design. Thirty-six children with thalassemia from Thalassemia Patients of Pasteur Hospital in Bam from October to December 2020 and were recruited and randomly allocated to two arms. The pain of venous cannulation (no treatment) was measured in the first blood transfusion session as control. In the second and third sessions, two arms received music and vapocoolant spray before the venous cannulation with a cross-over design. The intensity of pain was measured by a Visual Analogue Scale (VAS). The change in pain scores was tested by ANOVA and Tukey post-hoc test between three measurements. Results During and after the cannulation, the pain was significantly lower in the vapocoolant measurement than in control and music (p

Purpose: Evidence regarding the performance of digital dentures (DDs) fabricated using 3D printing is insufficient. This study aimed to evaluate patient satisfaction with conventional dentures (CDs) and DDs fabricated using 3D printing. Methods: This randomized controlled trial was conducted between November 2017 and May 2020. In the CD-DD group, CDs were fabricated before DDs, while the protocol was reversed in the DD-CD group. The primary outcome was patient satisfaction, quantified using a 100-mm visual analog scale, which assessed chewing efficiency, pain, stability, retention, comfort, esthetics, ease of cleaning, phonetics, and general satisfaction. Secondary outcomes were quality of life (QOL), number of visits, time required for definitive denture fabrication, number of adjustment appointments, and time required for denture stabilization after denture delivery. Results: Patient satisfaction with CDs was superior in terms of phonetics, ease of cleaning, stability, comfort, and general satisfaction. Secondary outcomes such as social disability and the number of clinic visits were significantly lower in patients with DDs. However, the two groups showed no significant differences in the other outcomes. Although patient satisfaction with DDs was inferior to that with CDs, 20% of patients preferred and used DDs (12 patients preferred CDs, and three patients opted for DDs). Conclusion: Although patient satisfaction or QOL with DDs may be somewhat inferior to that with CDs, 20% of patients preferred and used DDs daily. Thus, DDs fabricated using 3D printing may have comparable practicality and efficacy to CDs. [ABSTRACT FROM AUTHOR]

Abstract Background To compare clinical and psychological factors among patients with self-perceived statin-associated muscle symptoms (SAMS), confirmed SAMS, and refuted SAMS in coronary heart disease patients (CHD). Methods Data were obtained from a cross-sectional study of 1100 CHD outpatients and a study of 71 CHD outpatients attending a randomized, double-blinded, placebo-controlled, crossover study to test effects of atorvastatin 40 mg/day on muscle symptom intensity. Clinical and psychosocial factors were compared between patients with and without SAMS in the cross-sectional study, and between patients with confirmed SAMS and refuted SAMS in the randomized study. Results Bilateral, symmetric muscle symptoms in the lower extremities during statin treatment were more prevalent in patients with confirmed SAMS compared to patients with refuted SAMS (75% vs. 41%, p = 0.01) in the randomized study. No significant differences in psychological factors (anxiety, depression, worry, insomnia, type D personality characteristics) were detected between patients with and without self-perceived SAMS in the cross-sectional study, or between patients with confirmed SAMS and refuted SAMS, in the randomized study. Conclusions Patients with confirmed SAMS more often present with bilateral lower muscle symptoms compared to those with refuted SAMS. Psychological factors were not associated with self-perceived SAMS or confirmed SAMS. A careful pain history and a search for alternative causes of muscle symptoms are likely to promote communication in patients with SAMS, and may reduce the risk for statin discontinuation.

Background: The mainstay of treatment for diabetic peripheral neuropathic pain is pharmacotherapy, but the current National Institute for Health and Care Excellence guideline is not based on robust evidence, as the treatments and their combinations have not been directly compared. Objectives: To determine the most clinically beneficial, cost-effective and tolerated treatment pathway for diabetic peripheral neuropathic pain. Design: A randomised crossover trial with health economic analysis. Setting: Twenty-one secondary care centres in the UK. Participants: Adults with diabetic peripheral neuropathic pain with a 7-day average self-rated pain score of ≥ 4 points (Numeric Rating Scale 0–10). Interventions: Participants were randomised to three commonly used treatment pathways: (1) amitriptyline supplemented with pregabalin, (2) duloxetine supplemented with pregabalin and (3) pregabalin supplemented with amitriptyline. Participants and research teams were blinded to treatment allocation, using over-encapsulated capsules and matching placebos. Site pharmacists were unblinded. Outcomes: The primary outcome was the difference in 7-day average 24-hour Numeric Rating Scale score between pathways, measured during the final week of each pathway. Secondary end points included 7-day average daily Numeric Rating Scale pain score at week 6 between monotherapies, quality of life (Short Form questionnaire-36 items), Hospital Anxiety and Depression Scale score, the proportion of patients achieving 30% and 50% pain reduction, Brief Pain Inventory – Modified Short Form items scores, Insomnia Severity Index score, Neuropathic Pain Symptom Inventory score, tolerability (scale 0–10), Patient Global Impression of Change score at week 16 and patients’ preferred treatment pathway at week 50. Adverse events and serious adverse events were recorded. A within-trial cost–utility analysis was carried out to compare treatment pathways using incremental costs per quality-adjusted life-years from an NHS and social care perspective. Results: A total of 140 participants were randomised from 13 UK centres, 130 of whom were included in the analyses. Pain score at week 16 was similar between the arms, with a mean difference of –0.1 points (98.3% confidence interval –0.5 to 0.3 points) for duloxetine supplemented with pregabalin compared with amitriptyline supplemented with pregabalin, a mean difference of –0.1 points (98.3% confidence interval –0.5 to 0.3 points) for pregabalin supplemented with amitriptyline compared with amitriptyline supplemented with pregabalin and a mean difference of 0.0 points (98.3% confidence interval –0.4 to 0.4 points) for pregabalin supplemented with amitriptyline compared with duloxetine supplemented with pregabalin. Results for tolerability, discontinuation and quality of life were similar. The adverse events were predictable for each drug. Combination therapy (weeks 6–16) was associated with a further reduction in Numeric Rating Scale pain score (mean 1.0 points, 98.3% confidence interval 0.6 to 1.3 points) compared with those who remained on monotherapy (mean 0.2 points, 98.3% confidence interval –0.1 to 0.5 points). The pregabalin supplemented with amitriptyline pathway had the fewest monotherapy discontinuations due to treatment-emergent adverse events and was most commonly preferred (most commonly preferred by participants: amitriptyline supplemented with pregabalin, 24%; duloxetine supplemented with pregabalin, 33%; pregabalin supplemented with amitriptyline, 43%; p = 0.26). No single pathway was superior in cost-effectiveness. The incremental gains in quality-adjusted life-years were small for each pathway comparison [amitriptyline supplemented with pregabalin compared with duloxetine supplemented with pregabalin –0.002 (95% confidence interval –0.011 to 0.007) quality-adjusted life-years, amitriptyline supplemented with pregabalin compared with pregabalin supplemented with amitriptyline –0.006 (95% confidence interval –0.002 to 0.014) quality-adjusted life-years and duloxetine supplemented with pregabalin compared with pregabalin supplemented with amitriptyline 0.007 (95% confidence interval 0.0002 to 0.015) quality-adjusted life-years] and incremental costs over 16 weeks were similar [amitriptyline supplemented with pregabalin compared with duloxetine supplemented with pregabalin −£113 (95% confidence interval −£381 to £90), amitriptyline supplemented with pregabalin compared with pregabalin supplemented with amitriptyline £155 (95% confidence interval −£37 to £625) and duloxetine supplemented with pregabalin compared with pregabalin supplemented with amitriptyline £141 (95% confidence interval −£13 to £398)]. Limitations: Although there was no placebo arm, there is strong evidence for the use of each study medication from randomised placebo-controlled trials. The addition of a placebo arm would have increased the duration of this already long and demanding trial and it was not felt to be ethically justifiable. Future work: Future research should explore (1) variations in diabetic peripheral neuropathic pain management at the practice level, (2) how OPTION-DM (Optimal Pathway for TreatIng neurOpathic paiN in Diabetes Mellitus) trial findings can be best implemented, (3) why some patients respond to a particular drug and others do not and (4) what options there are for further treatments for those patients on combination treatment with inadequate pain relief. Conclusions: The three treatment pathways appear to give comparable patient outcomes at similar costs, suggesting that the optimal treatment may depend on patients’ preference in terms of side effects. Trial registration: The trial is registered as ISRCTN17545443 and EudraCT 2016-003146-89. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme, and will be published in full in Health Technology Assessment; Vol. 26, No. 39. See the NIHR Journals Library website for further project information.

Background: Venous cannulation is among the most stressful and painful experiences of children hospitalization. Children with thalassemia need regular blood transfusion which needs venous access each time. The quality of care and quality of life of children will be improved if appropriate methods are used to reduce pain. This study aimed to compare vapocoolant spray and music in the reduction of pain of Venous cannulation in children with thalassemia. Methods: The study was a randomized controlled clinical trial with a cross-over design. Thirty-six children with thalassemia from Thalassemia Patients of Pasteur Hospital in Bam from October to December 2020 and were recruited and randomly allocated to two arms. The pain of venous cannulation (no treatment) was measured in the first blood transfusion session as control. In the second and third sessions, two arms received music and vapocoolant spray before the venous cannulation with a cross-over design. The intensity of pain was measured by a Visual Analogue Scale (VAS). The change in pain scores was tested by ANOVA and Tukey post-hoc test between three measurements. Results: During and after the cannulation, the pain was significantly lower in the vapocoolant measurement than in control and music (p < 0.05). There was a significant effect of vapocoolant spray during the procedure F (2, 90) = 25.604, p = 0.001. Also, there was a significant effect of vapocoolant spray after the procedure F (2, 90) = 10.087, p = 0.004). Music did not reduce the pain during cannulation (p = 0.413) and after that (p = 0.807) significantly when compared with control. Conclusions: Vapocoolant was an effective method of pain reduction in the reduction of venous cannulation pain. Music was not effective in the reduction of venous cannulation pain when we compared it with controls. The pain of venous cannulation is rated as high and it can have negative effects on the children. There is a need to do more research on the methods of pain reduction of venous cannulation. Trial registration: The trial is registered: IRCT20111019007844N13, 13/03/2020. Available at: https://en.irct.ir/trial/42904. [ABSTRACT FROM AUTHOR]

Background & Aims: Metformin is a widely prescribed first line drug for the treatment of type 2 diabetes mellitus (DM). Studies have shown that the use of metformin is often associated with a decrease in vitamin B 12 (B 12 ) levels in patients with DM. Few studies have shown that this effect could be mitigated with calcium supplementation. In the present study, we quantified the effect of metformin, and metformin co-administered with calcium on B 12 absorption using a novel stable isotope [ 13 C] cyanocobalamin tracer., Methods: A pilot crossover study was conducted to estimate the bioavailability of B 12 in healthy subjects, using [ 13 C] cyanocobalamin as a tracer. In the study, [ 13 C] cyanocobalamin was administered orally to the participants followed by hourly venous sampling to measure the concentration of the tracer and estimate bioavailability. This protocol was followed for three experiment days, each separated by a one month wash out period. As part of the study, all participants received the tracer alone for the control day (C), metformin 850 mg along with the tracer for the metformin day (M) and metformin 850 mg with calcium 500 mg and the tracer for the metformin calcium day (MC)., Results: Seven participants completed all three experiment days. The mean B 12 bioavailability (±SD, n = 7) was 42.6 ± 10.2% for the control day (C), 30.8 ± 15.3% for the metformin day (M) and 46.4 ± 8.6% for the metformin-calcium day (MC). Repeated measures ANOVA was done and the pairwise comparison showed a significant difference in the B 12 bioavailability between control and metformin day (C vs M p = 0.010), and between the metformin and metformin with calcium day (M vs MC p = 0.003)., Conclusion: B 12 bioavailability reduced significantly from baseline (C) when metformin (M) was administered and this reduction was reversed when calcium was co-administered (MC) in healthy participants. In patients using metformin, calcium supplementation as a strategy to prevent B 12 deficiency needs to be further studied., Competing Interests: Declaration of competing interest No potential conflicts of interests to declare., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Kale ( Brassica oleracea species) is considered a functional food whose macronutrient and phytochemical contents are considered beneficial and widely considered as a superfood. In the present 6-week cross-over trial with a 2-week washout period, we compared the beneficial effects of freeze-dried kale over peas among Arab women with obesity. A total of 124 Saudi women with obesity were allocated to receive either freeze-dried kale ( n = 62) or freeze-dried peas ( n = 62) given in the form of 3-gram sachets thrice daily for 2 weeks, followed by a 2-week washout period and a cross-over of 4 weeks. Anthropometric measurements, glucose, lipids and markers of gut barrier function were assessed at baseline and post-intervention. Participants who took kale supplementation first resulted in significant weight reduction ( p = 0.02) which was not observed among those who took peas first. Participants receiving pea supplementation first experienced a significant decline in Hba1c ( p = 0.005) and CD14 ( p = 0.03), but C-peptide increased ( p = 0.05). Crossover analysis revealed significant carryover effects in most variables with non-significant combined treatment effects. Among the variables with no carryover effect with significant combined treatment effect include HbA1c which was in favor of the pea group ( p = 0.005) and C-peptide which was modestly in favor of the kale group ( p = 0.05). While both freeze dried kale and pea supplementation appear beneficial, supplementation of freeze-dried pea appears to be more effective in terms of acute glycemic control than kale. The study suggests that common but less-hyped vegetables such as pea maybe equally, if not more beneficial than the more expensive promoted superfoods such as kale. Longer clinical trials using a parallel design instead of cross-over are recommended to strengthen present findings., 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 © 2024 Aldisi, Sabico, Almiman, Al-Farraj, Basaeed, Wani, Hussain, Ansari, McTernan and Al-Daghri.)

Introduction: The optimal regional anticoagulation (RA) of dialysis filters in patients at risk of bleeding remains elusive. Inducing hypocalcemia within the filter by using a calcium-free dialysate has emerged as an easy-to-use heparin-free RA, including in critically ill patients, but comparative studies are lacking., Methods: We conducted a multicentre, randomized, crossover trial to compare the efficacy and tolerance of two RAs (heparin-coated membrane (HCM) or calcium free dialysate with calcium reinjection according to ionic dialysance (CFD)) in patients requiring hemodialysis and at risk of bleeding. During the study period, each patient received two dialysis sessions (one with each RA in a randomly assigned order). The primary endpoint was the proportion of dialysis sessions completed (≥ 240 min)., Results: 94 patients were included in the intention-to-treat analysis, including 16 critically ill patients (17.0%). Coagulation and inflammation parameters, as well as hemodynamic status at baseline, were balanced between groups. Premature coagulation of the filter occurred in 19 HCM (20.9%) compared to 3 (3.2%) CFD sessions. In half of the sessions with premature termination, coagulation occurred before 180 minutes. The proportion of patients who completed the CFD session while failing to complete the HCM session (n = 17) was significantly higher than the proportion of patients who completed the HCM session while failing to complete the CFD session (n = 1; p < 0.001). Hemodynamic and metabolic tolerance were not different between groups., Conclusions: In individuals at risk of bleeding, RA with calcium-free dialysate significantly reduces the incidence of premature dialysis termination compared to heparin-coated membrane without safety concerns. Trial registration and statistical analysis plan: ClinicalTrials.gov identifier: NCT03842657., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Cell culture and animal studies suggest puerarin could prevent cardiovascular disease (CVD). However, trials in human are scare, not primarily designed for prevention, and inadequately powered. We assessed the effect of puerarin supplementation on CVD risk factors in men using a crossover trial. Methods: In total, 217 Chinese men aged 18–50 years without a history of CVD were recruited. They were randomized to take a puerarin supplement (90.2 mg daily) or a placebo, followed by a 4-week wash-out period, and then crossed over to the other intervention. An intention-to-treat analysis was used. Differences in primary outcomes (lipid profile such as low-density lipoprotein (LDL) cholesterol) and secondary outcomes (other CVD risk factors such as blood pressure and fasting glucose, and some potential mediating pathways such as testosterone) between supplementation and placebo within participants were compared using a paired t-test, or a crossover (CROS)-based analysis where a period effect existed. Results: Lipid profile was similar after the puerarin supplementation or placebo (e.g., mean difference in LDL cholesterol: −0.02 mmol/L, 95% confidence interval (CI) −0.09 to −0.06). Conversely, fasting glucose was reduced after the puerarin supplementation (−0.13 mmol/L, 95% CI −0.25 to −0.008). There were no differences in blood pressure, testosterone, high-sensitive C-reactive protein, prothrombin time, liver or renal function. Conclusion: In young-to-middle-aged Chinese men, short-term puerarin supplementation did not improve the primary outcome of lipid profile, but an exploratory analysis suggested that puerarin could be beneficial for one of the secondary outcomes, i.e., fasting glucose.

Background: Endothelial dysfunction is an early pathophysiological feature and independent predictor of a poor prognosis in most forms of cardiovascular disease. We evaluated the effect of brown rice crackers (BR-C) on endothelial function. Methods: Effect of heat-moisture treated (HMT) -BR-C on postprandial flow-mediated dilation (FMD) in adults with mild endothelial dysfunction was compared with that of BR-C and white rice crackers (WR-C) in 12 adults with mild endothelial dysfunction (less than 7.0% of FMD) by a randomized, single-blind, three-treatment three-period crossover trial (UMIN 000034898). Since we considered that the FMD increase was associated with the treatment of HMT-BR-C, we examined the effect of three possible factors: postprandial glucose levels, polyphenol content, and polyphenol release from the food matrix. Results: Mean pre-intake baseline FMD values of HMT-BR-C, BR-C, and WR-C were 4.9%, 5.1%, and 4.9%, respectively, and those values 1 h post-intake were 6.3%, 5.1%, and 4.8%, respectively. There was no difference in intergroup comparisons of FMD using Dunnett's multiple comparison test. There was a significant increase in FMD only in HMT-BR-C in intragroup comparisons (P = 0.042 by paired-t test). In comparison with BR-C, no significant difference was noted in the postprandial glucose level nor in the content of total polyphenols and ferulic acid derivatives in HMT-BR-C. However, the 70% ethanol extracted from HMT-BR-C contained a significantly larger amount of free and bound ferulic acids than from BR-C. Conclusion: HMT-BR-C intake increased the postprandial FMD response.

Abstract Background There is an emerging body of evidence that links exposure to shift work to cardiovascular disease (CVD). The risk of coronary events, such as myocardial infarction, is greater among night shift workers compared to day workers. There is reason to believe that repeated exposure to shift work, especially night shift work, creates alterations in normal circadian patterns of blood pressure (BP) and heart rate variability (HRV) and that these alterations contribute to increased risk of CVD. Recent data suggest that allowing shift workers to nap during night shifts may help to normalize BP and HRV patterns and, over time, reduce the risk of CVD. The risk of CVD related to shift work is elevated for emergency medical services (EMS) shift workers due in part to long-duration shifts, frequent use of night shifts, and a high prevalence of multiple jobs. Methods We will use a randomized crossover trial study design with three study conditions. The targeted population is comprised of EMS clinician shift workers, and our goal enrollment is 35 total participants with an estimated 10 of the 35 enrolled not completing the study protocol or classified as lost to attrition. All three conditions will involve continuous monitoring over 72 h and will begin with a 36-h at-home period, followed by 24 total hours in the lab (including a 12-h simulated night shift), ending with 12 h at home. The key difference between the three conditions is the intra-shift nap. Condition 1 will involve a simulated 12-h night shift with total sleep deprivation. Condition 2 will involve a simulated 12-h night shift and a 30-min nap opportunity. Condition 3 will involve a simulated 12-h night shift with a 2-h nap opportunity. Our primary outcomes of interest include blunted BP dipping and reduced HRV as measured by the standard deviation of the inter-beat intervals of normal sinus beats. Non-dipping status will be defined as sleep hours BP dip of less than 10%. Discussion Our study will address two indicators of cardiovascular health and determine if shorter or longer duration naps during night shifts have a clinically meaningful impact. Trial registration ClinicalTrials.gov NCT04469803 . Registered on 9 July 2020

Introduction: Angiotensin receptor blockers (ARBs) are preferably used in hypertensive patients with CKD. Azilsartan is a strong antihypertensive ARB, but its antiproteinuric effects are not well understood. We compared the antiproteinuric effect of azilsartan and candesartan in CKD patients in an open-label, randomized, crossover trial. Methods: A total of 111 patients were treated with 20 mg of azilsartan daily for 2 months as a run-in period. After the run-in period, patients were randomized into 2 arms and received either 20 mg of azilsartan or 8 mg of candesartan daily for 3 months in a crossover trial. The primary outcome was the percent change in urinary protein-to-Cr ratio (UPCR). Results: Ninety-five patients completed the trial. The mean age was 64.3 years. The estimated glomerular filtration rate (eGFR) and UPCR were 41.5 mL/min/1.73 m2 and 1.8 g/gCr, respectively. The baseline systolic and diastolic blood pressures were 131.4 and 71.0 mm Hg, respectively. The mean percent change in the UPCR was −3.8% in the azilsartan group and 30.8% in the candesartan group at the 1st endpoint (p = 0.0004), and 6.1% in the azilsartan group and 25.8% in the candesartan group at the 2nd (final) endpoint (p = 0.029). The incidence of adverse events, including eGFR levels and serum potassium levels, was not significantly different between the groups. Conclusion: A 20 mg azilsartan dose had potent antiproteinuric effects compared with an 8 mg candesartan dose, without an increase in adverse events. Azilsartan may provide renal protection in addition to antihypertensive effects in CKD patients.

Purpose: Increased levels of uric acid (UA), which is mainly excreted through the kidneys, are independently associated with higher mortality in end-stage renal disease (ESRD) patients. The uricolysis of gut microbiota plays an important role in extrarenal excretion of UA. This study aimed to examine the effect of inulin-type prebiotics (a type of fermentable dietary fiber) on intestinal microbiota modulation and serum UA levels in ESRD patients. Methods: Continuous ambulatory peritoneal dialysis (CAPD) patients were recruited to a randomized, double-blind, placebo-controlled crossover trial of 12-week inulin-type prebiotics. Participants were visited before and after treatment with prebiotics or placebo. Serum UA levels, dietary purine intake, serum xanthine oxidase (XO) activity, daily "renal excretion" of UA, and fecal UA degradation capability were measured at each visit. Fecal metagenomic analysis was conducted to assess microbial composition and function. Results: Sixteen participants (mean age = 37 y; 10 men and 6 women) completed the trial, and 64 specimens were analyzed. The average concentration of serum UA decreased by approximately 10% in the prebiotic intervention group in comparison to the placebo group (p = 0.047) without an increase in daily "renal excretion" of UA via urine and dialysate. There were no significant changes in purine intake or activity of XO. Notably, enhanced fecal UA degradation was observed after prebiotic intervention (p = 0.041), and the ratio of Firmicutes/Bacteroidetes, which was positively associated with fecal UA degradation, increased in the prebiotic period (p = 0.032). Furthermore, prebiotics enriched purine-degrading species in the gut microbiota, including unclassified_o_Clostridiales, Clostridium sp. CAG:7, Clostridium sp. FS41, Clostridium citroniae, Anaerostipes caccae, and Clostridium botulinum. Conclusions: Inulin-type prebiotics is a promising therapeutic candidate to reduce serum UA levels in renal failure patients, and this urate-lowering effect could possibly be attributed to intestinal microbial degradation of UA. Trial registry: This study was registered at the Chinese Clinical Trials Registry (http://www.chictr.org.cn/), registration ID: ChiCTR-INR-17013739, registration date: 6th Dec 2017. [ABSTRACT FROM AUTHOR]

When there are multiple reference products, (e.g., EU-approved product and US-licensed product), a pharmacokinetic/pharmacodynamic (PK/PD) bridging study is often conducted in order to bridge the clinical data from the original region (e.g., Europe) to the new region (e.g., USA) in support of the biosimilar regulatory submission in the new region. The purpose is to avoid duplicated clinical trials for clinical similarity between a proposed biosimilar product and the reference product in the new region provided that there is no ethnic concern in the two regions. In this article, some innovative statistical designs for PK/PD biosimilar bridging studies are proposed. Statistical model and methods under the proposed statistical designs are studied. Power analysis for sample size requirement based on Schuirmann's two one-sided tests procedure is also derived and compared to pairwise testing using simulation. [ABSTRACT FROM AUTHOR]

Background Irritable bowel syndrome (IBS) has been associated with diets rich in fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs), and gluten. Most previous studies have been single-blind and have focused on the elimination of FODMAPs or provocation with single FODMAPs. The effect of gluten is unclear, large trials isolating the effect of gluten from that of FODMAPs are needed. Objectives The aims of this study were to ensure high intakes of a wide range of FODMAPs, gluten, or placebo, and to evaluate the effects on IBS symptoms using the IBS-severity scoring system (IBS-SSS). Methods The study was carried out with a double-blind, placebo-controlled, randomized 3-way crossover design in a clinical facility in Uppsala from September 2018 to June 2019. In all, 110 participants fulfilling the IBS Rome IV criteria, with moderate to severe IBS, were randomly assigned; 103 (90 female, 13 male) completed the trial. Throughout, IBS participants maintained a diet with minimal FODMAP content and no gluten. Participants were block-randomly assigned to 1-wk interventions with FODMAPs (50 g/d), gluten (17.3 g/d), or placebo, separated by 1-wk washout. All participants who completed ≥1 intervention were included in the intention-to-treat analysis. Results In participants with IBS (n  = 103), FODMAPs caused higher IBS-SSS scores (mean 240 [95% CI: 222, 257]) than placebo (198 [180, 215]; P  = 0.00056) or gluten (208 [190, 226]; P  = 0.013); no differences were found between the placebo and gluten groups (P  = 1.0). There were large interindividual differences in IBS-SSS scores associated with treatment. No adverse events were reported. Conclusion In participants with IBS, FODMAPs had a modest effect on typical IBS symptoms, whereas gluten had no effect. The large interindividual differences in responses to the interventions warrant further detailed studies to identify possible underlying causes and enable individual prediction of responses. This trial was registered at www.clinicaltrials.gov as NCT03653689. [ABSTRACT FROM AUTHOR]

Background: To compare clinical and psychological factors among patients with self-perceived statin-associated muscle symptoms (SAMS), confirmed SAMS, and refuted SAMS in coronary heart disease patients (CHD).Methods: Data were obtained from a cross-sectional study of 1100 CHD outpatients and a study of 71 CHD outpatients attending a randomized, double-blinded, placebo-controlled, crossover study to test effects of atorvastatin 40 mg/day on muscle symptom intensity. Clinical and psychosocial factors were compared between patients with and without SAMS in the cross-sectional study, and between patients with confirmed SAMS and refuted SAMS in the randomized study.Results: Bilateral, symmetric muscle symptoms in the lower extremities during statin treatment were more prevalent in patients with confirmed SAMS compared to patients with refuted SAMS (75% vs. 41%, p = 0.01) in the randomized study. No significant differences in psychological factors (anxiety, depression, worry, insomnia, type D personality characteristics) were detected between patients with and without self-perceived SAMS in the cross-sectional study, or between patients with confirmed SAMS and refuted SAMS, in the randomized study.Conclusions: Patients with confirmed SAMS more often present with bilateral lower muscle symptoms compared to those with refuted SAMS. Psychological factors were not associated with self-perceived SAMS or confirmed SAMS. A careful pain history and a search for alternative causes of muscle symptoms are likely to promote communication in patients with SAMS, and may reduce the risk for statin discontinuation. [ABSTRACT FROM AUTHOR]

Background: Chronotropic incompetence has shown to be associated with a decrease in exercise capacity in heart failure with preserved ejection fraction (HFpEF), yet β-blockers are commonly used in HFpEF despite the lack of robust evidence.Objectives: This study aimed to evaluate the effect of β-blocker withdrawal on peak oxygen consumption (peak Vo2) in patients with HFpEF and chronotropic incompetence.Methods: This is a multicenter, randomized, investigator-blinded, crossover clinical trial consisting of 2 treatment periods of 2 weeks separated by a washout period of 2 weeks. Patients with stable HFpEF, New York Heart Association functional classes II and III, previous treatment with β-blockers, and chronotropic incompetence were first randomized to withdrawing from (arm A: n = 26) versus continuing (arm B: n = 26) β-blocker treatment and were then crossed over to receive the opposite intervention. Changes in peak Vo2 and percentage of predicted peak Vo2 (peak Vo2%) measured at the end of the trial were the primary outcome measures. To account for the paired-data nature of this crossover trial, linear mixed regression analysis was used.Results: The mean age was 72.6 ± 13.1 years, and most of the patients were women (59.6%) in New York Heart Association functional class II (66.7%). The mean peakVo2 and peak Vo2% were 12.4 ± 2.9 mL/kg/min, and 72.4 ± 17.8%, respectively. No significant baseline differences were found across treatment arms. Peak Vo2 and peak Vo2% increased significantly after β-blocker withdrawal (14.3 vs 12.2 mL/kg/min [Δ +2.1 mL/kg/min]; P < 0.001 and 81.1 vs 69.4% [Δ +11.7%]; P < 0.001, respectively).Conclusions: β-blocker withdrawal improved maximal functional capacity in patients with HFpEF and chronotropic incompetence. β-blocker use in HFpEF deserves profound re-evaluation. (β-blockers Withdrawal in Patients With HFpEF and Chronotropic Incompetence: Effect on Functional Capacity [PRESERVE-HR]; NCT03871803; 2017-005077-39). [ABSTRACT FROM AUTHOR]

Stopping for futility is a useful tool in a clinical trial. It is widely used in single-arm trials in oncology and in many two-arm trials. We review three stopping rules for futility. We give recommendations for the optimal timing of futility looks in two-stage trials in terms of the information fraction and the probability of stopping under the alternative hypothesis. We discuss futility stopping in trials with substantial uncertainty about the variability of the outcome and in crossover trials. [ABSTRACT FROM AUTHOR]

Objective: Antibiotic overuse is one of the major prescription problems in rural China and a major risk factor for antibiotic resistance. Low antibiotic prescription rates can effectively reduce the risk of antibiotic resistance. We hypothesized that under a paperless, computer-based feedback system the rates of antibiotic prescriptions among primary care physicians can be reduced. Methods: A cluster randomized crossover open controlled trial was conducted in 31 hospitals. These hospitals were randomly allocated to two groups to receive the intervention for three months followed by no intervention for three months in a random sequence. The feedback intervention information, which displayed the physicians’ antibiotic prescription rates and ranking, was updated every 10 days. The primary outcome was the 10-day antibiotic prescription rate of the physicians. Results: There were 82 physicians in group 1 (intervention first followed by control) and 81 in group 2 (control first followed by intervention). Baseline comparison showed no significant difference in antibiotic prescription rate between the two groups (30.8% vs 35.2%, P-value = 0.07). At the crossover point, the relative reduction in antibiotic prescription rate was significantly higher among physicians in the intervention group than in the control group (33.1% vs 20.3%, P-value

Abstract Background This study aims to evaluate the effect of subcutaneous (SC) elamipretide dosing on exercise performance using the 6 min walk test (6MWT), patient‐reported outcomes measuring fatigue, functional assessments, and safety to guide the development of the Phase 3 trial. Methods MMPOWER‐2 was a randomized, double‐blind, placebo‐controlled, crossover trial that enrolled participants (N = 30) with genetically confirmed primary mitochondrial myopathy. Participants were randomly assigned (1:1) to 40 mg/day SC elamipretide for 4 weeks followed by placebo SC for 4 weeks, separated by a 4‐week washout period, or the opposite sequence. The primary endpoint was the distance walked on the 6MWT. Results The distance walked on the 6MWT by the elamipretide‐treated participants was 398.3 (±134.16) meters compared with 378.5 (±125.10) meters in the placebo‐treated group, a difference of 19.8 m (95% confidence interval, −2.8, 42.5; P = 0.0833). The results of the Primary Mitochondrial Myopathy Symptom Assessment Total Fatigue and Total Fatigue During Activities scores showed that participants treated with elamipretide reported less fatigue and muscle complaints compared with placebo (P = 0.0006 and P = 0.0018, respectively). Additionally, the Neuro‐QoL Fatigue Short Form and Patient Global Assessment showed reductions in symptoms (P = 0.0115 and P = 0.0421, respectively). In this 4‐week treatment period, no statistically significant change was observed in the Physician Global Assessment (P = 0.0636), the Triple Timed Up and Go (P = 0.8423) test, and wrist/hip accelerometry (P = 0.9345 and P = 0.7326, respectively). Injection site reactions were the most commonly reported adverse events with elamipretide (80%), the majority of which were mild. No serious adverse events or deaths were reported. Conclusions Participants who received a short‐course treatment of daily SC elamipretide for 4 weeks experienced a clinically meaningful change in the 6MWT, which did not achieve statistical significance as the primary endpoint of the study. Secondary endpoints were suggestive of an elamipretide treatment effect compared with placebo. Nominal statistically significant and clinically meaningful improvements were seen in patient‐reported outcomes. The results of this trial provided an efficacy signal and data to support the initiation of MMPOWER‐3, a 6‐month long, Phase 3 treatment trial in patients with primary mitochondrial myopathy.

Abstract Background This study aimed to evaluate the effectiveness of a customized interactive video game-based (IVGB) training on balance in older adults with mild-to-moderate Parkinson’s disease (PD). Methods In this 12-week crossover trial, PD patients ≥65 years of age were randomly divided into Group A (a 6-week intervention phase followed by a 6-week control phase) and Group B (a 6-week control phase followed by a 6-week intervention phase). Participants received IVGB exercise training during the intervention phase and no exercise during the control phase. Functional outcomes were measured using behavioral evaluation scales and questionnaires at baseline, week 6 and week 12. Results Twenty-four PD patients were included in this study, and were evenly divided into two groups. After Bonferroni adjustment, the changes in Modified Falls Efficacy Scale (MFES) and two subscales of Multi-Directional Reach Test were significantly different between two groups in the first 6-week period. In addition, the changes in Berg Balance Scale, MFES, and two subscales of Maximum Step Length were significantly different between two groups in the second 6-week period. Compared to controls, 6-week IVGB exercise intervention significantly improved different but overlapping functional outcomes in two groups of PD patients. Conclusions The customized IVGB exercise training improves balance, postural stability and confidence in preventing falls in older adults with mild-to-moderate PD. However, this IVGB exercise doesn’t have a significant impact on quality of life. Trial registration ClinicalTrials.gov. NCT03689764 . Registered 27 September 2018, retrospectively registered.

Abstract Background Dementia is a neurological condition that affects the cognitive and functional ability of the brain and is the leading cause of disability among those aged 65 years and above. More effective ways to manage dementia symptoms are needed because current treatment options (antidepressants and antipsychotics) can be ineffective and are associated with substantial side effects, including increased rate of mortality. Cannabinoid-based medicine (CBM) has shown an ability to inhibit some symptoms associated with dementia, and the adverse effects are often minimal; yet, little research has explored the use of CBM among this population. Aim To monitor the safety of a purified dose of CBM oil (3:2 delta-9-tetrahydrocannabinol:cannabidiol) on behaviour symptoms, quality of life and discomfort caused by pain. Methods/design We will carry out an 18-week, randomised, double-blind crossover trial that consists of a 2-week eligibility period, two 6-week treatment cycles, and two 2-week washout periods (between both cycles and after the second treatment cycle). We aim to recruit 50 participants with dementia who are living in residential aged-care facilities. The participants will be randomised into two groups and will receive a dose of either CBM oil or placebo for the first treatment cycle and the opposite medication for the second. Data will be collected using the Neuropsychiatric Inventory Questionnaire, the Cohen-Mansfield Agitation Inventory, the Quality of Life in Alzheimer’s Disease questionnaire, and the Abbey Pain Scale on seven occasions. These will be completed by the participants, aged-care staff, and nominated next of kin or family members. The participants’ heart rate and blood pressure will be monitored weekly, and their body composition and weight will be monitored fortnightly by a research nurse, to assess individual dose response and frailty. In addition, pre- and post-surveys will be administered to aged-care staff and family members to understand their perceptions of CBM and to inform proposed focus groups consisting of the aged-care staff and next of kin. Discussion The study design has been informed by medical professionals and key stakeholders, including those working in the residential aged-care industry to ensure patient safety, collection of non-invasive measures, and methodological rigor and study feasibility. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12619000474156. Registered on 21 March 2019

Abstract Background Crossover designs are commonly utilised in randomised controlled trials investigating treatments for long-term chronic illnesses. One problem with this design is its inherent repeated measures necessitate the availability of an estimate of the within-person standard deviation (SD) to perform a sample size calculation, which may be rarely available at the design stage of a trial. Interim sample size re-estimation designs can be used to help alleviate this issue by adapting the sample size mid-way through the trial, using accrued information in a statistically robust way. Methods The AIM HY-INFORM study is part of the Informative Markers in Hypertension (AIM HY) Programme and comprises two crossover trials, each with a planned recruitment of 600 participants. The objective of the study is to test whether blood pressure response to first line antihypertensive treatment depends on ethnicity. An interim analysis is planned to reassess the assumptions of the planned sample size for the study. The aims of this paper are: (1) to provide a formula for sample size re-estimation in both crossover trials; and (2) to present a simulation study of the planned interim analysis to investigate alternative within-person SDs to that assumed. Results The AIM HY-INFORM protocol sample size calculation fixes the within-person SD to be 8 mmHg, giving > 90% power for a primary treatment effect of 4 mmHg. Using the method developed here and simulating the interim sample size reassessment, if we were to see a larger within-person SD of 9 mmHg at interim, 640 participants for 90% power 90% of the time in the three-period three-treatment design would be required. Similarly, in the four-period four-treatment crossover design, 602 participants would be required. Conclusions The formulas presented here provide a method for re-estimating the sample size in crossover trials. In the context of the AIM HY-INFORM study, simulating the interim analysis allows us to explore the results of a possible increase in the within-person SD from that assumed. Simulations show that without increasing the planned sample size of 600 participants, we can reasonably still expect to achieve 80% power with a small increase in the within-person SD from that assumed. Trial registration ClinicalTrials.gov, NCT02847338. Registered on 28 July 2016.

Background: Labor pain varies significantly among pregnant women, ranging from mild to extremely distressing. Nonpharmacologic pain relief methods during vaginal birth are increasingly popular, either as a complement to pharmacologic agents or, at times, as the primary method of pain relief. Multiple trials have reported that manual or by-hand massage reduces labor pain. The effectiveness of full-body mechanical massage using electric massage chairs on labor pain remains unexplored., Objective: This study aimed to evaluate mechanical massage using an electric massage chair on labor pain in nulliparous women., Study Design: A randomized counterbalanced crossover trial was conducted in a university hospital in Malaysia from August 2022 to February 2023. Eligible nulliparas in labor with a minimum labor pain score of 5 (0-10 numerical rating scale) were enrolled. Participants were randomized to 30 minutes on the massage chair with mechanical massage followed by 30 minutes on the massage chair without mechanical massage or the other way around in the massage sequence. The primary outcome was a change in pain score comparing pain with and without mechanical massage as a paired comparison for the entire trial participants. The secondary outcomes were across arms analyses of maternal and neonatal outcomes. The paired t test, t test, Mann-Whitney U test, chi-square test, and Fisher exact test were used as appropriate for the data., Results: Overall, 208 women were randomized: 104 to each intervention. Data were available from 204 participants (103 randomized to massage first and 101 to no massage first). The primary outcomes of change in labor pain scores (0-10 numerical rating scale) after massage and no massage (all participants included after crossover, paired t test analysis) were 4.51±2.30 and 5.38±2.10, respectively (mean difference, -0.87; 95% confidence interval, -1.14 to -0.59; P<.001), a significant reduction in pain score after electric chair mechanical massage compared with no massage. On the across randomized arms secondary analyses, labor pain scores after their first massage chair session were 4.35±2.52 (randomized to massage first, received massage as initial intervention) and 5.66±1.73 (randomized to no massage first, received no massage as initial intervention) (mean difference, -1.31; 95% confidence interval, -1.91 to -0.748; P<.001), a significant reduction after mechanical massage. Other distal maternal outcomes (mode of delivery, labor analgesia, duration of labor, and maternal agreement that mechanical massage is effective for labor pain) and neonatal outcomes (Apgar scores at 1 and 5 minutes, cord artery blood pH and base excess, and neonatal admission) were not different across randomized arms., Conclusion: Mechanical massage using an electric massage chair significantly reduced labor pain, offering a potential nonpharmacologic pain management option during labor., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Most people who begin statins abandon them, most commonly because of side effects.Objectives: The purpose of this study was to assess daily symptom scores on statin, placebo, and no treatment in participants who had abandoned statins.Methods: Participants received 12 1-month medication bottles, 4 containing atorvastatin 20 mg, 4 placebo, and 4 empty. We measured daily symptom intensity for each using an app (scale 1-100). We also measured the "nocebo" ratio: the ratio of symptoms induced by taking statin that was also induced by taking placebo.Results: A total of 60 participants were randomized and 49 completed the 12-month protocol. Mean symptom score was 8.0 (95% CI: 4.7-11.3) in no-tablet months. It was higher in statin months (16.3; 95% CI: 13.0-19.6; P < 0.001), but also in placebo months (15.4; 95% CI: 12.1-18.7; P < 0.001), with no difference between the 2 (P = 0.388). The corresponding nocebo ratio was 0.90. In the individual-patient daily data, neither symptom intensity on starting (OR: 1.02; 95% CI: 0.98-1.06; P = 0.28) nor extent of symptom relief on stopping (OR: 1.01; 95% CI: 0.98-1.05; P = 0.48) distinguished between statin and placebo. Stopping was no more frequent for statin than placebo (P = 0.173), and subsequent symptom relief was similar between statin and placebo. At 6 months after the trial, 30 of 60 (50%) participants were back taking statins.Conclusions: The majority of symptoms caused by statin tablets were nocebo. Clinicians should not interpret symptom intensity or timing of symptom onset or offset (on starting or stopping statin tablets) as indicating pharmacological causation, because the pattern is identical for placebo. (Self-Assessment Method for Statin Side-effects Or Nocebo [SAMSON]; NCT02668016). [ABSTRACT FROM AUTHOR]

Abstract Background The number of people with diabetes is growing rapidly. Diabetes can cause nerve damage leading to severe pain in the feet, legs and hands, which is known as diabetic peripheral neuropathic pain (DPNP). In the UK, the National Institute for Health and Care Excellence (NICE) recommends amitriptyline, duloxetine, pregabalin or gabapentin as initial treatment for DPNP. If this is not effective, adding one of the other drugs in combination with the first is recommended. NICE points out that these recommendations are not based on robust evidence. The OPTION-DM randomised controlled trial has been designed to address this evidence deficit, with the aims of determining the most clinically beneficial, cost-effective and tolerated treatment pathway for patients with DPNP. Methods/design A multicentre, double-blind, centre-stratified, multi-period crossover study with equal allocation to sequences (1:1:1:1:1:1) of treatment pathways. Three hundred and ninety-two participants will be recruited from secondary care DPNP centres in the UK. There are three treatment pathways: amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline and duloxetine supplemented with pregabalin. All participants will receive all three pathways and randomisation will determine the order in which they are received. The primary outcome is the difference between 7-day average 24-h pain scores on an 11-point NRS scale measured during the final follow-up week of the treatment pathway. Secondary outcomes for efficacy, cost-effectiveness, safety, patient-perceived tolerability and subgroup analysis will be measured at week 6 and week 16 of each pathway. Discussion The study includes direct comparisons of the mainstay treatment for DPNP. This novel study is designed to examine treatment pathways and capture clinically relevant outcomes which will make the results generalisable to current clinical practice. The study will also provide information on health economic outcomes and will include a subgroup study to provide information on whether patient phenotypes predict response to treatment. Trial registration ISRCTN17545443. Registered on 12 September 2016.

Background: There is an emerging body of evidence that links exposure to shift work to cardiovascular disease (CVD). The risk of coronary events, such as myocardial infarction, is greater among night shift workers compared to day workers. There is reason to believe that repeated exposure to shift work, especially night shift work, creates alterations in normal circadian patterns of blood pressure (BP) and heart rate variability (HRV) and that these alterations contribute to increased risk of CVD. Recent data suggest that allowing shift workers to nap during night shifts may help to normalize BP and HRV patterns and, over time, reduce the risk of CVD. The risk of CVD related to shift work is elevated for emergency medical services (EMS) shift workers due in part to long-duration shifts, frequent use of night shifts, and a high prevalence of multiple jobs.Methods: We will use a randomized crossover trial study design with three study conditions. The targeted population is comprised of EMS clinician shift workers, and our goal enrollment is 35 total participants with an estimated 10 of the 35 enrolled not completing the study protocol or classified as lost to attrition. All three conditions will involve continuous monitoring over 72 h and will begin with a 36-h at-home period, followed by 24 total hours in the lab (including a 12-h simulated night shift), ending with 12 h at home. The key difference between the three conditions is the intra-shift nap. Condition 1 will involve a simulated 12-h night shift with total sleep deprivation. Condition 2 will involve a simulated 12-h night shift and a 30-min nap opportunity. Condition 3 will involve a simulated 12-h night shift with a 2-h nap opportunity. Our primary outcomes of interest include blunted BP dipping and reduced HRV as measured by the standard deviation of the inter-beat intervals of normal sinus beats. Non-dipping status will be defined as sleep hours BP dip of less than 10%.Discussion: Our study will address two indicators of cardiovascular health and determine if shorter or longer duration naps during night shifts have a clinically meaningful impact.Trial Registration: ClinicalTrials.gov NCT04469803 . Registered on 9 July 2020. [ABSTRACT FROM AUTHOR]