Intake of Pistachios as a Nighttime Snack Has Similar Effects on Short- and Longer-Term Glycemic Control Compared with Education to Consume 1-2 Carbohydrate Exchanges in Adults with Prediabetes: A 12-Wk Randomized Crossover Trial.

BACKGROUND: Nut intake is associated with better glycemic control and lower cardiovascular disease (CVD) risk. It remains unclear if nut intake timing affects glycemic control and CVD risk factors. Intake of pistachios as a nighttime snack may attenuate morning glucose production and lower fasting plasma glucose (FPG). OBJECTIVES: We assessed the effects of a nighttime (after dinner and before bedtime) pistachio snack (57 g/d) on glycemic control markers, vascular health, lipids/lipoproteins, and diet quality compared with education to consume 1-2 carbohydrate (CHO) exchanges (usual care) in individuals with prediabetes. METHODS: A 2-period, randomized crossover trial was conducted. Participants were provided 57 g/d of dry roasted unsalted pistachios (319 kcal; fat 26 g; CHO 16 g; protein 12 g; fiber 6 g) as a nighttime snack or received usual care for 12 wk. Primary (FPG) and secondary outcomes [hemoglobin A1c (HbA1c), insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), lipids/lipoproteins, vascular health, and Healthy Eating Index-2015 (HEI-2015)] were measured before and after each condition. RESULTS: A total of 66 participants (50.9 ± 11.6 y, FPG: 106.2 ± 6.4 mg/dL) were randomly assigned, and 51 participants completed the trial. No between-condition differences in FPG {0.9 mg/dL [95% confidence interval (CI): -1.2, 3.1]}, HbA1c, insulin, HOMA-IR, lipids/lipoproteins, blood pressure, or vascular health were observed. The HEI-2015 score was higher after the pistachio condition [6.8 points (95% CI: 1.5, 12.1)] than after usual care driven by higher component scores for seafood and plant proteins [2.0 points (95% CI: 1.0, 2.9)], refined grains [2.3 points (95% CI: 1.1, 3.5)], and the fatty acid ratio [1.7 points (95% CI: 0.0, 3.5)]. CONCLUSIONS: In adults with prediabetes, consuming 57 g/d of pistachios as a nighttime snack increased diet quality but had similar effects on glycemic markers, lipids/lipoproteins, blood pressure, and vascular health compared with the usual care comparator. Pistachios may be a healthful alternative to carbohydrate-rich nighttime snacks to increase alignment with Dietary Guidelines for Americans. This trial was registered at clinicaltrials.gov as NCT04056208.

A randomized crossover trial of regional anticoagulation modalities for intermittent hemodialysis.

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 efficacy of ball blankets on insomnia in depression in outpatient clinics: A randomised crossover multicentre trial.

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.

Complete denture palatal rugae design impact on satisfaction and quality of life.

OBJECTIVES: To compare the impact of three complete denture palatal rugae designs on participants' satisfaction and oral-health-related quality of life. BACKGROUND: Complete dentures palatal rugea are usually polished to a smooth finish, which can affect the patient's adaptation. Roughening or keeping an opening in the rugae area to replicate the natural sensation of the palatal rugae has been suggested but lacks clinical evidence. METHODS: This randomised crossover trial included participants with complete dentures randomly allocated to six sequences. Each sequence alternated between polished, roughened, and open rugae designs. Participants evaluated general and domain-specific satisfaction (eating, taste, speaking, phonetics, and ease of cleaning) on a 100-mm visual analogue scale. They also completed the Oral Health Impact Profile for Edentulous Patients (OHIP-EDENT) and indicated their preferred design at the end. Repeated-measure ANOVA compared satisfaction, and one-way ANOVA with Tukey's test compared OHIP-EDENT scores. RESULTS: Forty-two participants were randomised. Seven dropped out. General satisfaction ratings were comparable for the polished (Mean = 80.2, SD = 19.7) and roughened designs (Mean = 79.5, SD = 20.2). However, the open design had a significantly lower satisfaction rating (Mean = 41.1, SD = 32.2). OHIP-EDENT scores for the open design (Mean = 44.9, SD = 17.5) were significantly worse than those for the polished (Mean = 36.1, SD = 12.7) and roughened designs (Mean = 36.2, SD = 13.3). Two-thirds of the participants chose the polished design. One-third chose the roughened design; of those, 83% were first-time denture wearers. CONCLUSIONS: Complete dentures with polished and roughened rugae designs were perceived similarly. Both designs could be recommended based on the patient's preference. However, the open design should be avoided due to negative perception.

The effect of silver fibre gloves on Raynaud's phenomenon in patients with systemic sclerosis: a double-blind randomized crossover trial.

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 [ß = 0.067 (95% CI -0.006, 0.19)]. Of secondary outcomes, total SHAQ [ß = 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.

Norepinephrine versus phenylephrine for treating hypotension during general anaesthesia in adult patients undergoing major noncardiac surgery: a multicentre, open-label, cluster-randomised, crossover, feasibility, and pilot trial.

BACKGROUND: Intraoperative hypotension is associated with postoperative complications. The use of vasopressors is often required to correct hypotension but the best vasopressor is unknown. METHODS: A multicentre, cluster-randomised, crossover, feasibility and pilot trial was conducted across five hospitals in California. Phenylephrine (PE) vs norepinephrine (NE) infusion as the first-line vasopressor in patients under general anaesthesia alternated monthly at each hospital for 6 months. The primary endpoint was first-line vasopressor administration compliance of 80% or higher. Secondary endpoints were acute kidney injury (AKI), 30-day mortality, myocardial injury after noncardiac surgery (MINS), hospital length of stay, and rehospitalisation within 30 days. RESULTS: A total of 3626 patients were enrolled over 6 months; 1809 patients were randomised in the NE group, 1817 in the PE group. Overall, 88.2% received the assigned first-line vasopressor. No drug infiltrations requiring treatment were reported in either group. Patients were median 63 yr old, 50% female, and 58% white. Randomisation in the NE group vs PE group did not reduce readmission within 30 days (adjusted odds ratio=0.92; 95% confidence interval, 0.6-1.39), 30-day mortality (1.01; 0.48-2.09), AKI (1.1; 0.92-1.31), or MINS (1.63; 0.84-3.16). CONCLUSIONS: A large and diverse population undergoing major surgery under general anaesthesia was successfully enrolled and randomised to receive NE or PE infusion. This pilot and feasibility trial was not powered for adverse postoperative outcomes and a follow-up multicentre effectiveness trial is planned. CLINICAL TRIAL REGISTRATION: NCT04789330 (ClinicalTrials.gov).

Serious gaming and virtual reality in the multimodal training of laparoscopic inguinal hernia repair: a randomized crossover study.

BACKGROUND: The aim of this study was to assess the transferability of surgical skills for the laparoscopic hernia module between the serious game Touch Surgery™ (TS) and the virtual reality (VR) trainer Lap Mentor™. Furthermore, this study aimed to collect validity evidence and to discuss "sources of validity evidence" for the findings using the laparoscopic inguinal hernia module on TS. METHODS: In a randomized crossover study, medical students (n = 40) in their clinical years performed laparoscopic inguinal hernia modules on TS and the VR trainer. TS group started with "Laparoscopic Inguinal Hernia Module" on TS (phase 1: Preparation, phase 2: Port Placement and Hernia Repair), performed the module first in training, then in test mode until proficiency was reached. VR group started with "Inguinal Hernia Module" on the VR trainer (task 1: Anatomy Identification, task 2: Incision and Dissection) and also performed the module until proficiency. Once proficiency reached in the first modality, the groups performed the other training modality until reaching proficiency. Primary endpoint was the number of attempts needed to achieve proficiency for each group for each task/phase. RESULTS: Students starting with TS needed significantly less attempts to reach proficiency for task 1 on the VR trainer than students who started with the VR trainer (TS = 2.7 ± 0.6 vs. VR = 3.2 ± 0.7; p = 0.028). No significant differences for task 2 were observed between groups (TS = 2.3 ± 1.1 vs. VR = 2.1 ± 0.8; p = 0.524). For both phases on TS, no significant skill transfer from the VR trainer to TS was observed. Aspects of validity evidence for the module on TS were collected. CONCLUSION: The results show that TS brought additional benefit to improve performances on the VR trainer for task 1 but not for task 2. Skill transfer from the VR trainer to TS could not be shown. VR and TS should thus be used in combination with TS first in multimodal training to ensure optimal training conditions.

Measurement equivalence of the paper-based and electronic version of the Integrated Palliative care Outcome Scale (IPOS): A randomised crossover trial.

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.

Chemical behavior of 20%-22% carbamide peroxide gels in at-home bleaching: Randomized crossover in situ trial.

OBJECTIVE: To evaluate if distinct 20%-22% carbamide peroxide bleaching gels present similar decomposition pattern and pH during the clinical use in both arches, as well as gels viscosity. METHODS: Participants randomly received treatments with carbamide peroxide gels (n = 10): OPF (OpalescencePF-20%); PNT (Polanight-22%); and WPC (Whiteness Perfect-22%) in three different days, with 2-day washout. Decomposition pattern was assessed by peroxide concentration. Both PC and pH of bleaching gels were measured in different time points in upper and lower trays during a total of 120 min of clinical use. Viscosity of bleaching gels was measured in triplicate. ANOVA and Tukey's test were applied (α = 0.05). RESULTS: Regarding decomposition pattern, no significant differences were observed for the interaction between gel, time, and tray position factors. The peroxide concentration progressively reduced until 120 min of trays use (p < 0.001), being overall more notable in lower trays (p < 0.001). Regarding pH, the lowest values were verified in WPC within time. At 120 min, an increase of pH was observed for both WPC and OPF (p < 0.001) compared to baseline means. PNT exhibited constant pH values over time. The values of viscosity were: OPF (1.682.000 ± 19 cP)a, WPC (1.388.667 ± 172.63 cP)ab, PNT (579.567 ± 0.98 cP)b. CONCLUSIONS: The bleaching gels presented overall decomposition pattern clinically equivalent, being more notable in lower trays over time. Nevertheless, distinct pH and viscosities were observed among the products. CLINICAL SIGNIFICANCE: Although the manufacturers recommend different times of use for bleaching gels with similar peroxide concentrations, the commercial products tested did not exhibit clinically relevant difference in the decomposition pattern during the 120 min of clinical procedure.

Efficacy of titratable mandibular advancement device versus continuous positive airway pressure therapy in the treatment of obstructive sleep apnea: A clinical crossover trial.

Background: To compare efficacy of continuous positive airway pressure (CPAP) and oral appliance (OA) in management of various grades of obstructive sleep apnea (OSA). Methods: 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. Results: 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). Conclusions: 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.

Survival analyses from the CENTAUR trial in amyotrophic lateral sclerosis: Evaluating the impact of treatment crossover on outcomes.

INTRODUCTION/AIMS: Trials incorporating placebo-to-active treatment crossover are encouraged in fatal conditions like amyotrophic lateral sclerosis (ALS) but may underestimate active treatment survival benefit. Here, we apply methods for modeling survival without crossover, including the rank-preserving structural failure time model (RPSFTM), to data from the CENTAUR trial of sodium phenylbutyrate and taurursodiol (PB and TURSO) in ALS incorporating both randomized placebo-controlled and open-label extension (OLE) phases. METHODS: Intent-to-treat (ITT) and RPSFTM survival analyses were performed with final data at a July 2020 cutoff date. Analyses of subgroups based on randomized treatment and OLE phase participation were also performed. RESULTS: Hazard ratios (95% confidence intervals) of death for PB and TURSO versus participants initially on placebo were 0.57 (0.35-0.92) on ITT analysis and 0.39 (0.17-0.88) in the primary on-treatment RPSFTM analysis (p = .023). Median ITT survival duration for PB and TURSO (25.8 mo) was 6.9 mo longer than placebo (18.9 mo) on ITT analysis and 10.6 mo longer than the median RPSFTM-adjusted survival duration for placebo (15.2 mo). Median survival duration was 18.8 mo longer in the PB and TURSO-randomized subgroup who continued into the OLE phase versus the placebo-randomized subgroup who did not continue into the OLE phase (p < .0001), although OLE phase selection bias may have potentially confounded these results. DISCUSSION: Similar to the prespecified ITT analysis, post hoc analyses adjusting for treatment crossover in CENTAUR showed a significant survival benefit for PB and TURSO. Such methods may provide clinical context for observed survival outcomes in future ALS crossover trials.

Inulin-type prebiotics reduce serum uric acid levels via gut microbiota modulation: a randomized, controlled crossover trial in peritoneal dialysis 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.

Comparison of music and vapocoolant spray in reducing the pain of venous cannulation in children age 6-12: a randomized clinical trial.

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 .

Vascular benefits of vitamin C supplementation against fine particulate air pollution in healthy adults: A double-blind randomised crossover trial.

Evidence on the health benefits of vitamin C supplementation in highly polluted areas has not been evaluated. We aimed to evaluate whether dietary vitamin C supplementation can improve vascular health linked to particulate matter (PM) exposure. A randomised double-blind crossover trial involving 58 health young adults was performed in Shijiazhuang, China in 2018. All subjects were randomly assigned to the vitamin C supplementation group (2000 mg/d) or placebo group for a week alternating with a 2 week washout period. Fifteen circulating biomarkers were measured. Linear mixed-effect model was applied to evaluate the effect of vitamin C supplementation on health outcomes. The average concentrations of PM2.5 and PM10 were 164.91 and 327.05 µg/m3, respectively. Vitamin C supplementation was significantly associated with a 19.47% decrease in interleukin-6 (IL-6), 17.30% decrease in tumour necrosis factor-a (TNF-α), 34.01% decrease in C-reactive protein (CRP), 3.37% decrease in systolic blood pressure (SBP) and 6.03% decrease in pulse pressure (PP). Furthermore, glutathione peroxidase (GSH-Px) was significantly increased by 7.15%. Sex-subgroup analysis showed that vitamin C significantly reduced TNF-α by 27.85% in male participants and significantly increased APOB by 6.28% and GSH-Px by 14.47% only in female participants. This study indicated that vitamin C supplementation may protect vascular vessels against PM exposure among healthy young adults in China.

The effect of Dioscorea esculenta powder on prostaglandin E2 and cytochrome c oxidase subunit 2 levels, menstrual pain, and premenstrual syndrome in young women: A randomized double-blind controlled trial.

Background Diosgenin, extracted from Dioscorea esculenta, has been reported to decrease prostaglandin E2 (PGE2) levels and any other inflammatory cytokine in rodents. However, it is still unclear whether D. esculenta intake suppressed PGE2 production and menstrual pain and premenstrual syndrome (PMS) in younger female. Aim This study aims to investigate the effect of D. esculenta intake on PGE2 and cytochrome c oxidase subunit 2 (COX-2) levels and on menstrual pain and PMS in young women. This is a randomized, double-blind, placebo-controlled, crossover study. Methods Ten healthy young females were administered either a placebo or D. esculenta (300 mg/day) for 4 weeks, followed by a 4-week washout period. Fasting blood sample was taken from the fingertips on the second day of menstrual cycle began and obtained 24h before the last D. esculenta to avoid acute effects. Participants then switched treatments for 4 weeks as a second trial. Plasma PGE2 and COX-2 levels were measured before and after each trial. The visual analogue scale (VAS), McGill pain questionnaire (MPQ), and Daily Record of Severity of Problems (DRSP) were also evaluated. The study was set and conducted from 2019 to 2020. Results PGE2 and COX-2 levels significantly decreased after D. esculenta intake compared to placebo (p = 0.038, p = 0.042 each). The VAS and DRSP scores were also significantly lower after D. esculenta intake (p = 0.046, p = 0.035 each). Conclusion Four-week D. esculenta intake suppressed PGE2 and COX-2 levels resulting in an improvement in PMS symptoms and menstrual pain in young women.

Information content of stepped wedge designs with unequal cluster-period sizes in linear mixed models: Informing incomplete designs.

In practice, stepped wedge trials frequently include clusters of differing sizes. However, investigations into the theoretical aspects of stepped wedge designs have, until recently, typically assumed equal numbers of subjects in each cluster and in each period. The information content of the cluster-period cells, clusters, and periods of stepped wedge designs has previously been investigated assuming equal cluster-period sizes, and has shown that incomplete stepped wedge designs may be efficient alternatives to the full stepped wedge. How this changes when cluster-period sizes are not equal is unknown, and we investigate this here. Working within the linear mixed model framework, we show that the information contributed by design components (clusters, sequences, and periods) does depend on the sizes of each cluster-period. Using a particular trial that assessed the impact of an individual education intervention on log-length of stay in rehabilitation units, we demonstrate how strongly the efficiency of incomplete designs depends on which cells are excluded: smaller incomplete designs may be more powerful than alternative incomplete designs that include a greater total number of participants. This also serves to demonstrate how the pattern of information content can be used to inform a set of incomplete designs to be considered as alternatives to the complete stepped wedge design. Our theoretical results for the information content can be extended to a broad class of longitudinal (ie, multiple period) cluster randomized trial designs.

Clinical and psychological factors in coronary heart disease patients with statin associated muscle side-effects.

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.

Stronger Effect of Azilsartan on Reduction of Proteinuria Compared to Candesartan in Patients with CKD: A Randomized Crossover Trial.

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.

Analgesic Efficacy of "Burst" and Tonic (500 Hz) Spinal Cord Stimulation Patterns: A Randomized Placebo-Controlled Crossover Study.

OBJECTIVES: The aim of this study was to compare the efficacy in reducing pain intensity in adult subjects suffering from chronic back and leg pain of burst (BST) and tonic sub-threshold stimulation at 500 Hz (T500) vs. sham stimulation delivered by a spinal cord stimulation (SCS) device capable of automated postural adjustment of current intensity. MATERIALS AND METHODS: A multicentre randomized double-blind, three-period, three-treatment, crossover study was undertaken at two centers in the United Kingdom. Patients who had achieved stable pain relief with a conventional SCS capable of automated postural adjustment of current intensity were randomized to sequences of BST, T500, and sham SCS with treatment order balanced across the six possible sequences. A current leakage was programmed into the implantable pulse generator (IPG) in the sham period. The primary outcome was patient reported pain intensity using a visual analog scale (VAS). RESULTS: Nineteen patients were enrolled and randomized. The mean reduction in pain with T500 was statistically significantly greater than that observed with either sham (25%; 95% CI, 8%-38%; p = 0.008) or BST (28%; 95% CI, 13%-41%; p = 0.002). There were no statistically significant differences in pain VAS for BST versus Sham (5%; 95% CI, -13% to 27%; p = 0.59). Exploratory sub-group analyses by study site and sex were also conducted for the T500 vs. sham and BST versus sham comparisons. CONCLUSIONS: The findings suggest a superior outcome versus sham from T500 stimulation over BST stimulation and a practical equivalence between BST and sham in a group of subjects with leg and back pain habituated to tonic SCS and having achieved a stable status with stimulation.

Sample size and power calculations for open cohort longitudinal cluster randomized trials.

When calculating sample size or power for stepped wedge or other types of longitudinal cluster randomized trials, it is critical that the planned sampling structure be accurately specified. One common assumption is that participants will provide measurements in each trial period, that is, a closed cohort, and another is that each participant provides only one measurement during the course of the trial. However some studies have an "open cohort" sampling structure, where participants may provide measurements in variable numbers of periods. To date, sample size calculations for longitudinal cluster randomized trials have not accommodated open cohorts. Feldman and McKinlay (1994) provided some guidance, stating that the participant-level autocorrelation could be varied to account for the degree of overlap in different periods of the study, but did not indicate precisely how to do so. We present sample size and power formulas that allow for open cohorts and discuss the impact of the degree of "openness" on sample size and power. We consider designs where the number of participants in each cluster will be maintained throughout the trial, but individual participants may provide differing numbers of measurements. Our results are a unification of closed cohort and repeated cross-sectional sample results of Hooper et al (2016), and indicate precisely how participant autocorrelation of Feldman and McKinlay should be varied to account for an open cohort sampling structure. We discuss different types of open cohort sampling schemes and how open cohort sampling structure impacts on power in the presence of decaying within-cluster correlations and autoregressive participant-level errors.