Crossover Study Research Articles

A Randomized Crossover Study in Single-Sided Deafness Comparing a Cartilage Conduction CROS System and an Air-Conduction CROS System.

To investigate if cartilage conduction (CC) rerouting devices are noninferior to air-conduction (AC) rerouting devices for single-sided deafness (SSD) patients by measuring objective and subjective performance using speech-in-noise tests that resemble a realistic hearing environment, sound localization tests, and standardized questionnaires. Prospective, single-subject randomized, crossover study. Anechoic room inside a university. Nine adults between 21 and 58 years of age with severe or profound unilateral sensorineural hearing loss. Patients' baseline hearing was assessed; they then used both the cartilage conduction contralateral routing of signals device (CC-CROS) and an air-conduction CROS hearing aid (AC-CROS). Patients wore each device for 2 weeks in a randomly assigned order. Three main outcome measures were 1) speech-in-noise tests, measuring speech reception thresholds; 2) proportion of correct sound localization responses; and 3) scores on the questionnaires, "Abbreviated Profile of Hearing Aid Benefit" (APHAB) and "Speech, Spatial, and Qualities of Hearing Scale" with 12 questions (SSQ-12). Speech reception threshold improved significantly when noise was ambient, and speech was presented from the front or the poor-ear side with both CC-CROS and AC-CROS. When speech was delivered from the better-ear side, AC-CROS significantly improved performance, whereas CC-CROS had no significant effect. Both devices mainly worsened sound localization, whereas the APHAB and SSQ-12 scores showed benefits. CC-CROS has noninferior hearing-in-noise performance except when the speech was presented to the better ear under ambient noise. Subjective measures showed that the patients realized the effectiveness of both devices.

Pharmacokinetic Comparison of a Fixed-Dose Combination of Candesartan Cilexetil/Amlodipine/Atorvastatin Versus Co-administration of Individual Formulations in Healthy Participants.

Fixed-dose combinations (FDCs) of angiotensinII receptor blockers, calcium channel blockers, and statins are conventional therapeutic interventions prescribed for cardiovascular diseases. This study aimed at drawing a comparison between the pharmacokinetics and safety of an FDC and the corresponding individual formulations in healthy subjects. A randomized, open-label, single-dose, three-sequence, three-period, partially repeated crossover study was conducted with a cohort of healthy volunteers. A 14-day washout period was maintained between each of the three periods. In this study, candesartan cilexetil, amlodipine, and atorvastatin was administered orally as FDCs of 16/10/40mg in study1 and 16/5/20mg in study2. The maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of candesartan, amlodipine, and atorvastatin were estimated as the geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of the FDC to individual formulations. If the within-subject coefficient of variation (CVwr) of Cmax was greater than 0.3, the bioequivalence (BE) range calculated using the reference-scaled average bioequivalence was used to assess whether the 90%CI was within the BE range. The GMRs (90%CIs) for the AUClast for candesartan and amlodipine were 0.9612 (0.9158-1.0089)/0.9965 (0.9550-1.0397) and 1.0033 (0.9800-1.0271)/1.0067 (0.9798-1.0344), and the GMRs (90%CIs) for Cmax were 0.9600 (0.8953-1.0294)/0.9851 (0.9368-1.0359) and 1.0198 (0.9950-1.0453)/1.0003 (0.9694-1.0321) in studies1 and 2, respectively. The extended BE ranges calculated from the CVwr of the Cmax of atorvastatin were 0.7814-1.2797 and 0.7415-1.3485, respectively. The GMRs (90%CIs) for the AUClast of atorvastatin were 1.0532 (1.0082-1.1003)/1.0252 (0.9841-1.0680), and the GMRs (90%CIs) for Cmax were 1.0630 (0.9418-1.1997)/0.9888 (0.8792-1.1120) in studies1 and 2, respectively. The Cmax and AUClast values of candesartan cilexetil/amlodipine/atorvastatin 16/10/40mg and 16/5/20mg, respectively, were within the BE ranges. There were no clinically significant differences in safety between the two formulations. ClinicalTrials.gov identifier, study1: NCT04478097; study2: NCT04627207.

Impact of nocturnal hypoxia on glycaemic control, appetite, gut microbiota and inflammation in adults with type 2 diabetes mellitus: A single-blind cross-over trial.

High altitude residents have a lower incidence of type 2 diabetes mellitus (T2DM). Therefore, we examined the effect of repeated overnight normobaric hypoxic exposure on glycaemic control, appetite, gut microbiota and inflammation in adults with T2DM. Thirteen adults with T2DM [glycated haemoglobin (HbA1c): 61.1±14.1mmolmol-1; aged 64.2±9.4years; four female] completed a single-blind, randomised, sham-controlled, cross-over study for 10 nights, sleeping when exposed to hypoxia (fractional inspired O2 [ ]=0.155; ∼2500m simulated altitude) or normoxic conditions ( =0.209) in a randomised order. Outcome measures included: fasted plasma [glucose]; [hypoxia inducible factor-1α]; [interleukin-6]; [tumour necrosis factor-α]; [interleukin-10]; [heat shock protein 70]; [butyric acid]; peak plasma [glucose] and insulin sensitivity following a 2h oral glucose tolerance test; body composition; appetite indices ([leptin], [acyl ghrelin], [peptide YY], [glucagon-like peptide-1]); and gut microbiota diversity and abundance [16S rRNA amplicon sequencing]. During intervention periods, accelerometers measured physical activity, sleep duration and efficiency, whereas continuous glucose monitors were used to assess estimated HbA1c and glucose management indicator and time in target range. Overnight hypoxia was not associated with changes in any outcome measure (P>0.05 with small effect sizes) except fasting insulin sensitivity and gut microbiota alpha diversity, which exhibited trends (P=0.10; P=0.08 respectively) for a medium beneficial effect (d=0.49; d=0.59 respectively). Ten nights of overnight moderate hypoxic exposure did not significantly affect glycaemic control, gut microbiome, appetite, or inflammation in adults with T2DM. However, the intervention was well tolerated and a medium effect-size for improved insulin sensitivity and reduced alpha diversity warrants further investigation. KEY POINTS: Living at altitude lowers the incidence of type 2 diabetes mellitus (T2DM). Animal studies suggest that exposure to hypoxia may lead to weight loss and suppressed appetite. In a single-blind, randomised sham-controlled, cross-over trial, we assessed the effects of 10 nights of hypoxia (fractional inspired O2 ∼0.155) on glucose homeostasis, appetite, gut microbiota, inflammatory stress ([interleukin-6]; [tumour necrosis factor-α]; [interleukin-10]) and hypoxic stress ([hypoxia inducible factor 1α]; heat shock protein 70]) in 13 adults with T2DM. Appetite and inflammatory markers were unchanged following hypoxic exposure, but an increased insulin sensitivity and reduced gut microbiota alpha diversity were associated with a medium effect-size and statistical trends, which warrant further investigation using a definitive large randomised controlled trial. Hypoxic exposure may represent a viable therapeutic intervention in people with T2DM and particularly those unable or unwilling to exercise because barriers to uptake and adherence may be lower than for other lifestyle interventions (e.g. diet and exercise).

Effects of Breaking up Sitting on Gut Hormone Responses and Subsequent Compensatory Behaviours in Physically Inactive Adults.

The effects of breaking up sitting on gut hormone responses and free-living energy compensatory behaviours are still unclear in people of Asian ethnicity. 26 Asians including 13 lean individuals (Lean) and 13 individuals with centrally overweight/obesity (OW), aged between 20 to 45 years, completed a randomized crossover study with either 5.5-h uninterrupted sitting (SIT) or 5.5-h sitting with 2 min walking at 6.4 km/h every 20 min (ACTIVE) in the laboratory. Blood samples were collected at regular time-points to examine postprandial glucagon-like peptide 1 (GLP-1), peptide YY (PYY) and glucose-dependent insulinotropic polypeptide (GIP) concentrations. Free-living physical activity and energy intake were recorded using wearable devices and weighed food diaries outside the laboratory until midnight. Paired t-tests were conducted to compare responses between trials. Postprandial GLP-1 and PYY incremental area under curve values were higher in the ACTIVE trial versus SIT in both Lean and OW groups (all, p < 0.05), but there was no difference in GIP in either group (both, p > 0.05). There were no differences in free-living physical activity (volume and intensity) or energy intake (total and macronutrients) between trials in either group (all, p > 0.05), resulting in greater total physical activity over the 24-h monitoring period in ACTIVE trial versus SIT trial (both, p < 0.05). Breaking up sitting increases postprandial GLP-1 and PYY concentrations in Asians, but does not induce subsequent behavioural compensation, resulting in greater 24-h physical activity levels and lower relative energy intake, in inactive individuals irrespective of bodyweight status.

Network-targeted transcranial direct current stimulation of the hypothalamus appetite-control network: a feasibility study.

The hypothalamus is the key regulator for energy homeostasis and is functionally connected to striatal and cortical regions vital for the inhibitory control of appetite. Hence, the ability to non-invasively modulate the hypothalamus network could open new ways for the treatment of metabolic diseases. Here, we tested a novel method for network-targeted transcranial direct current stimulation (net-tDCS) to influence the excitability of brain regions involved in the control of appetite. Based on the resting-state functional connectivity map of the hypothalamus, a 12-channel net-tDCS protocol was generated (Neuroelectrics Starstim system), which included anodal, cathodal and sham stimulation. Ten participants with overweight or obesity were enrolled in a sham-controlled, crossover study. During stimulation or sham control, participants completed a stop-signal task to measure inhibitory control. Overall, stimulation was well tolerated. Anodal net-tDCS resulted in faster stop signal reaction time (SSRT) compared to sham (p = 0.039) and cathodal net-tDCS (p = 0.042). Baseline functional connectivity of the target network correlated with SSRT after anodal compared to sham stimulation (p = 0.016). These preliminary data indicate that modulating hypothalamus functional network connectivity via net-tDCS may result in improved inhibitory control. Further studies need to evaluate the effects on eating behavior and metabolism.

Impact of Hydrocolloid Dressing and Moisturizing Cream as Facial Skin Protectants Among Health Care Workers.

During the novel coronavirus disease 2019 pandemic, health care workers experienced facial problems from prolonged use of N95 masks, including skin irritation, pigmentation changes, and contact dermatitis. We assessed the use of hydrocolloid dressing versus dimethicone cream to prevent skin breakdown among military health care workers while wearing an N95. Participants were recruited using convenience and snowball sampling in this nonblinded, randomized, cross-over study with 2 active treatments, hydrocolloid dressing and dimethicone cream, across 3 time points. The skin was assessed using photographs and subepidermal moisture scanner (SEM). N95 seal integrity was assessed using qualitative fit test. Institutional review board approval was obtained from the Madigan Army Medical Center Institutional Review Board. Among the 73 participants, wearing an N95 alone versus with dimethicone cream or hydrocolloid dressing caused more adverse skin reactions. There were no significant differences in qualitative fit test failure rate between groups. Participants experienced minimal to no dizziness, loss of energy/tiredness/fatigue, claustrophobia, shortness of breath, difficulty breathing, and dry or itchy eyes. For all interventions, wearing an N95 did not interfere with participants' concentration, verbal communication, hearing, vision, and, importantly, delivery of care. Using a skin protectant with an N95 may prevent adverse skin reactions while preserving health care workers' ability to safely and competently care for patients in routine and pandemic conditions.

Acute Effects of Slow, Moderate and Fast Tempo Dynamic Stretching Exercises on Power in Well-Trained Male Wrestlers

Due to the potential detrimental effects of static stretching exercises on subsequent muscle power performance, athletes and trainers have started to replace static stretching with dynamic stretching exercises in their training routines. However, there are no well-accepted guidelines regarding dynamic stretching variables, including tempo/velocity, volume (reps and sets), etc. Therefore, this study aimed to evaluate the acute effects of slow, moderate, and fast tempo dynamic stretching exercises on jump height, relative power, the reactive strength index, and leg stiffness in well-trained male wrestlers. Seventeen wrestlers (aged 20.00 ± 4.06 years, wrestling experience 6.00 ± 3.09 years, and training volume per week 10.00 ± 5.69 hours) took part in the experiment under four conditions (control session, slow tempo dynamic stretching, moderate tempo dynamic stretching, and fast tempo dynamic stretching) on separate days with a 72-h interval in between, following a randomized, crossover study design. The control session consisted of a 10-min jog on a motor-driven treadmill at 6 km/h and a 0% slope. Dynamic stretching sessions consisted of seven dynamic stretching exercises performed at 50 bpm, 100 bpm, and 120 bpm, following a 5-min warm-up on a treadmill at 6 km/h and a 0% slope. After each condition, wrestlers performed a 2 x 30-s repeated vertical jump test with 5-min rest intervals in between. The best results for jump height, relative power, the reactive strength index, and leg stiffness were registered for statistical analysis. One-way repeated ANOVA results demonstrated that there were no significant differences in pairwise comparisons of all variables obtained after the four different conditions (p &gt; 0.05). Overall, none of the slow, moderate, and fast tempo dynamic stretching exercises led to a change in repeated jump performance of well-trained male athletes. Further studies are needed to clarify the acute effects of different tempo dynamic stretching on muscular performance in well-trained wrestlers.

Performance on clinical outcomes, activities of daily living anduser experience on head-mounted displays for people withvision impairment.

To compare the objective performance, acceptance and usability of head-mounted displays (HMDs) to provide evidence-based data that could be used to increase the efficiency of device referrals based upon a person's vision loss and functional needs. A cross-sectional, counterbalanced, individually controlled crossover study was performed on 15 adults with various eye conditions. Performance was measured when using four HMDs: eSight4, Eyedaptic EYE3, Eyedaptic EYE4 and IrisVision Inspire. Performance on clinical visual acuity tests and contrast were assessed, as well as vision-related activities of daily living (ADL) which were divided into three categories: Reading, Searching & Identifying and Eye-hand Coordination. User-experience was also assessed. Logistic regression analyses, Friedman one-way repeated measure analyses of variance by ranks and multivariate permutation testing were used for analysis. There was a significant improvement in visual acuity when using all devices. For contrast tasks, only the eSight4 and Eyedaptic EYE3 improved performance relative to baseline. For most Reading and Searching & Identifying tasks, the odds of being able to perform the tasks were significantly higher while using the devices. However, the actual performance with most devices (e.g., number of words read or reading speed) did not improve significantly over baseline for most tasks. For the Eye-hand Coordination tasks, participants performed equivalent to or significantly poorer than baseline when using the devices. No demographic or clinical predictors of outcomes were identified. Participants expressed dissatisfaction with the devices' effectiveness, acceptability and usability. While performance on clinical tests was better when using the devices, performance on most real-world ADLs was equal to or worse than baseline. No single device improved performance on all tasks, and performance on any one task was not improved with all the devices. The overall dissatisfaction with the devices paralleled the lack of objective improvement in the performance of real-world tasks.

Effect of olfactory stimulation from aromatherapy on the autonomic nervous activity during aerobic exercises

Variations in the autonomic nervous system activity during exercise therapy in patients with cardiovascular diseases may lead to adverse events. Aromatherapy may reduce these adverse events by enhancing parasympathetic nervous activity (PNA). However, the effects of aromatherapy during exercise remain relatively unknown. This study aimed to evaluate the effect of aromatherapy on autonomic nervous activity during exercise and recovery. This randomized crossover study included 20 healthy men subjected to both aroma and placebo conditions which involved rest and moderate-intensity aerobic exercise on a cycle ergometer, followed by recovery. Blood pressure, heart rate variability indices, and SpO2 were measured during the rest, exercise, and recovery phases. Moreover, aroma preferences and emotional changes in response to the aroma were assessed. Under the placebo condition, high frequency (HF), root mean square of successive differences indices, and heart rate showed delayed recovery (P < 0.05). Furthermore, a moderate positive correlation was identified between aroma preference, pleasant emotions induced by aromatherapy, and the HF index (P < 0.05). These results indicate that aromatherapy facilitates the recovery of PNA after exercise. Furthermore, these effects were more pronounced among individuals who exhibited a stronger preference for and more positive emotions toward aromas.

Pharmacokinetics and Bioequivalence of Fixed-Dose Combination of Simvastatin and Ezetimibe Tablets: A Randomized, Crossover, Open-Label Study in Healthy Volunteers.

The current study aimed to evaluate the bioequivalence of a new generic combination of simvastatin and ezetimibe with the reference formulation. An open-label, randomized, 3-period, 3-sequence, crossover study, including 60 healthy volunteers, was implemented. Participants received the test and reference formulation, each containing 20mg of simvastatin and 10mg of ezetimibe as a single-dose tablet, separated by a minimum of 2-week washout periods. Blood samples were collected for 20 time points from predose to 72 hours after the dose. The total ezetimibe assay was carried out using a validated liquid chromatography-tandem mass spectrometry, while unconjugated ezetimibe, simvastatin, and simvastatin β-hydroxy acid determination was done via a validated ultra-performance liquid chromatography-tandem mass spectrometry. Each assay was preceded by a liquid-liquid extraction step. The pharmacokinetic parameters were derived using noncompartmental analysis and then compared between the reference and test formulations via a multivariate analysis of variance. No statistical difference was found in under the concentration-time curve from time 0 to the last quantifiable concentration and maximum concentration of unconjugated ezetimibe, total ezetimibe, and simvastatin between the reference and test formulations. The 90% confidence intervals of unconjugated ezetimibe, total ezetimibe, and simvastatin natural log-transformed under the concentration-time curve from time 0 to the last quantifiable concentration, and maximum concentration were in the range of 80%-125% as per the bioequivalence acceptance criteria. Therefore, the test formulation was bioequivalent to the reference formulation.

Effects of phytosterol supplementation on lipoprotein subfractions and LDL particle quality

Phytosterols are natural components of plant-based foods used as supplements because of their known cholesterol-lowering effect. However, their effects on lipoprotein subfractions and the quality of the LDL particle have not been studied in greater detail. We aimed to evaluate the effects of phytosterols supplements on lipids, lipoproteins subfractions, and on the quality of LDL. A prospective, pilot-type, open label, cross-over study, randomized 23 males in primary prevention of hypercholesterolemia to receive diet or diet plus phytosterol (2.6 g in 2 doses, with meals) for 12 weeks, when treatments were switched for another 12 weeks. Lipoprotein subfractions were analyzed by electrophoresis in polyacrylamide gel (Lipoprint System®). The Sampson equation estimated the small and dense (sd) and large and buoyant (lb) LDL subfractions from the lipid profile. Quality of LDL particle was analyzed by Z-scan and UV–vis spectroscopy. Primary outcome was the comparison of diet vs. diet plus phytosterols. Secondary outcomes assessed differences between baseline, diet and diet plus phytosterol. Non-parametric statistics were performed with p < 0.05. There was a trend to reduction on HDL-7 (p = 0.05) in diet plus phytosterol arm, with no effects on the quality of LDL particles. Heatmap showed strong correlations (ρ > 0.7) between particle size by different methods with both interventions. Diet plus phytosterol reduced TC, increased HDL-c, and reduced IDL-B, whereas diet increased HDL7, and reduced IDL-B vs. baseline (p < 0.05, for all). Phytosterol supplementation demonstrated small beneficial effects on HDL-7 subfraction, compared with diet alone, without effects on the quality of LDL particles.This trial is registered in Clinical Trials (NCT06127732) and can be accessed at https://clinicaltrials.gov.

Methodological Quality of Clinical Trials in Amyotrophic Lateral Sclerosis: A systematic Review.

More than 200 clinical trials have been performed worldwide in ALS so far, but no agents with substantial efficacy on disease progression have been found. To describe the methodological quality of all clinical trials performed in ALS and published before December 31, 2022. We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta Analyses. 213 trials were included. 47.4% manuscripts described preclinical study evaluation, with a positive effect in all. 67.6% of trials were conducted with a parallel-arm design, while 12.7% were cross-over studies; 77% were randomized, while in 5.6% historical-controls were used for comparison. 70% of trials were double blind. Participant inclusion allowed forced vital capacity (or corresponding slow vital capacity)<50% in 15% cases, between 55-65% in 21.6%, between 70-80% in 14.1% reports, and 49.3% of the evaluated manuscripts did not provide a minimum value for respiratory capacity at inclusion. Disease duration was < 6-months in 6 studies, 7-36 months in 68, 37-60 months in 24, 8 trials requested more than 1-month of disease duration, while in 107 reports a disease duration was not described. Dropout rate was ≥20% in 30.5% trials, while it was not reported for 8.5% . The methodological quality of the included studies was highly variable. Major issues to be addressed in future ALS clinical trials include: the requirement for standard animal toxicology and phase I studies, the resource-intensive nature of phase II-III studies, adequate study methodology and design, a good results reporting.

Assessment of the role of false-positive alerts in computer-aided polyp detection for assistance capabilities.

False positives (FPs) pose a significant challenge in the application of artificial intelligence (AI) for polyp detection during colonoscopy. The study aimed to quantitatively evaluate the impact of computer-aided polyp detection (CADe) systems' FPs on endoscopists. The model's FPs were categorized into four gradients: 0-5, 5-10, 10-15, and 15-20 FPs per minute (FPPM). Fifty-six colonoscopy videos were collected for a crossover study involving 10 endoscopists. Polyp missed rate (PMR) was set as primary outcome. Subsequently, to further verify the impact of FPPM on the assistance capability of AI in clinical environments, a secondary analysis was conducted on a prospective randomized controlled trial (RCT) from Renmin Hospital of Wuhan University in China from July 1 to October 15, 2020, with the adenoma detection rate (ADR) as primary outcome. Compared with routine group, CADe reduced PMR when FPPM was less than 5. However, with the continuous increase of FPPM, the beneficial effect of CADe gradually weakens. For secondary analysis of RCT, a total of 956 patients were enrolled. In AI-assisted group, ADR is higher when FPPM≤5 compared with FPPM>5 (CADe group: 27.78% vs 11.90%; P=0.014; odds ratio [OR], 0.351; 95% confidence interval [CI], 0.152-0.812; COMBO group: 38.40% vs 23.46%, P=0.029; OR, 0.427; 95% CI, 0.199-0.916). After AI intervention, ADR increased when FPPM≤5 (27.78% vs 14.76%; P=0.001; OR, 0.399; 95% CI, 0.231-0.690), but no statistically significant difference was found when FPPM>5 (11.90% vs 14.76%, P=0.788; OR, 1.111; 95% CI, 0.514-2.403). The level of FPs of CADe does affect its effectiveness as an aid to endoscopists, with its best effect when FPPM is less than 5.

The Effects of Displaying the Time Targets of the Manchester Triage System to Emergency Department Personnel: Prospective Crossover Study.

The use of triage systems such as the Manchester Triage System (MTS) is a standard procedure to determine the sequence of treatment in emergency departments (EDs). When using the MTS, time targets for treatment are determined. These are commonly displayed in the ED information system (EDIS) to ED staff. Using measurements as targets has been associated with a decline in meeting those targets. This study investigated the impact of displaying time targets for treatment to physicians on processing times in the ED. We analyzed the effects of displaying time targets to ED staff on waiting times in a prospective crossover study, during the introduction of a new EDIS in a large regional hospital in Germany. The old information system version used a module that showed the time target determined by the MTS, while the new system version used a priority list instead. Evaluation was based on 35,167 routinely collected electronic health records from the preintervention period and 10,655 records from the postintervention period. Electronic health records were extracted from the EDIS, and data were analyzed using descriptive statistics and generalized additive models. We evaluated the effects of the intervention on waiting times and the odds of achieving timely treatment according to the time targets set by the MTS. The average ED length of stay and waiting times increased when the EDIS that did not display time targets was used (average time from admission to treatment: preintervention phase=median 15, IQR 6-39 min; postintervention phase=median 11, IQR 5-23 min). However, severe cases with high acuity (as indicated by the triage score) benefited from lower waiting times (0.15 times as high as in the preintervention period for MTS1, only 0.49 as high for MTS2). Furthermore, these patients were less likely to receive delayed treatment, and we observed reduced odds of late treatment when crowding occurred. Our results suggest that it is beneficial to use a priority list instead of displaying time targets to ED personnel. These time targets may lead to false incentives. Our work highlights that working better is not the same as working faster.

Cyclic Meditation and Sleep Quality: A Review

Abstract Objectives Insufficient sleep leads to several short- and long-term physical and mental consequences. Yoga is a popularly known complementary health approach that maintains physical and mental health through asanas, meditation, and breathing techniques. Cyclic meditation (CM), derived from one of the Upanishads, is practiced by combining physical postures (asanas) with relaxation techniques. Recent findings emphasize the significance of CM as a means to enhance sleep quality. The current review aims to find the effects of CM on sleep quality through the available scientific data. Methods The current review includes research articles evaluating CM's effect on sleep quality from various databases such as PubMed, Cochrane, Embase, and Google Scholar up to January 22, 2023. We conducted a literature search using keywords related to CM and sleep quality, and search results were restricted to studies published in the English language. Results There were 5 articles with 277 participants meeting inclusion criteria, all conducted in India. Of those, 2 were randomized controlled trials and 3 were single-group or two-group pre-post and crossover studies. Participants ranged from healthy volunteers, type-2 diabetic patients, alcohol dependents, and caregivers for special needs children. Based on the available scientific evidence, CM has been found to be effective (d = 0.56–4.90) in enhancing the quality of sleep. Conclusion The CM technique could be tentatively considered as a beneficial practice to improve sleep. However, further, adequately powered, and randomized controlled studies with various other parameters of sleep are required to strongly recommend CM as a stand-alone yogic intervention for sleep disturbance.

Validation of a bupropion, dextromethorphan, and omeprazole cocktail for simultaneous phenotyping of cytochrome P450 2B11, 2D15, and 3A12 activities in dogs.

Develop a cytochrome P450 (CYP) phenotyping cocktail for dogs using specific substrates for hepatic P450 enzymes CYP2B11, CYP2D15, and CYP3A12 and determine whether alternative sampling methods (saliva and urine) or single time point samples could be used instead of multiple blood sampling. 12 healthy client-owned dogs (8 females and 4 males) from February 2019 to May 2019. In a randomized crossover study, dogs received oral administration of the probe drug bupropion (75 mg), dextromethorphan (30 mg), or omeprazole (40 mg) alone or as a 3-drug combination (Program in Individualized Medicine [PrIMe] cocktail) to evaluate simultaneous phenotyping of CYP2B11, CYP2D15, and CYP3A12. Pharmacokinetic profiles for the probe drugs and metabolites were determined using plasma, saliva, and urine. Dogs received probe drugs alone or combined. Pharmacokinetic profiles up to 6 hours postdose for the probe drugs and metabolites were determined using plasma, saliva, and urine. The PrIMe cocktail was well tolerated. There was no statistically significant interaction between the probe drugs when administered together. Single time point plasma metabolic ratios at 4 hours postdose for all probe drugs strongly correlated with the corresponding area under the plasma concentration-versus-time curve (AUC) ratios. Saliva AUC metabolic ratios for CYP3A12 and CYP2D15 and 6-hour urine for CYP2B11 and CYP2D15 were correlated with plasma AUC ratios. The PrIMe cocktail can be used for simultaneous CYP phenotyping using plasma 4-hour single time point sample metabolic ratios. Saliva and urine sampling are suitable for specific CYPs. The PrIMe cocktail has potential as a useful tool in dogs to detect clinically important CYP-mediated drug-drug interactions, identify novel pharmacogenes, determine the drug-metabolizing phenotype of individual dogs, aid in individualized dose selection, and evaluate the effects of various physiological states on drug metabolism.

A randomised, crossover trial exploring the patient perspective and effectiveness of biosimilar adalimumab transition: IBD reference and biosimilar adalimumab cross over study (iBaSS).

Patient satisfaction has been positively associated with adherence which is expected to impact outcomes. Although vital for successful implementation of biosimilar medicines, little is known about the patient perspective of transition. The aim of this study was to investigate clinical outcomes and patient experience of transitioning between reference adalimumab and a biosimilar (SB5). iBaSS is a phase IV single-centre, prospective, randomised, single-blind, cross-over study in adult subjects with Crohn's disease. Participants, stable on adalimumab before consent, received 24weeks of treatment with both reference adalimumab and SB5. The primary outcome was the proportion of patients maintaining baseline clinical status throughout each treatment period, with patients' perspective of disease control and treatment satisfaction assessed as secondary outcomes. A total of 112 participants, representative of the heterogeneous patient populations encountered in routine clinical practice, were enrolled. A similar proportion of participants maintained baseline clinical status through each treatment period: 81.8% with reference adalimumab and 79.5% with SB5. Patient reported outcomes (IBD-Control questionnaire (SB5: 15.5; reference adalimumab 15) and TSQM), adverse events and therapeutic drug monitoring remained consistent through both treatment periods, although a higher median injection pain VAS score was noted with SB5 (53/100 versus 6/100 with reference adalimumab). The number of switches undertaken in the study did not impact serum drug concentration or immunogenicity. This study, mimicking real world adalimumab transition, demonstrates that patients undertaking brand transition can be expected to have consistent clinical and satisfaction outcomes. Number 2018-004967-30.

The Effect of Myofascial Stretching on Mechanical Nociception and Contributing Neural Mechanisms

Myofascial stretching is often prescribed in the management of musculoskeletal pain. However, the neural mechanisms contributing to a decrease in pain are unknown. Stretching produces a sensation that may act as a conditioning stimulus in a conditioned pain modulation response. The purpose of this study was to compare immediate changes in pressure pain thresholds (PPTs) during a low-intensity stretch, moderate-intensity stretch, and cold water immersion task. A secondary purpose was to examine if personal pain sensitivity and psychological characteristics were associated with the responses to these interventions. Twenty-seven (27) healthy participants underwent a cross-over study design in which they completed a cold water immersion task, upper trapezius stretch to the onset of the stretch sensation, and a moderate-intensity stretch. A significant condition x time effect was observed (F (8,160) = 2.85, p &lt; 0.01, partial eta2 = 0.13), indicating reductions in pain sensitivity were significantly greater during a cold water immersion task compared to moderate-intensity stretching at minutes two and four. Widespread increases in heat pain threshold and lower pain-related anxiety were moderately correlated with the response to the cold water immersion task but not stretching. Moderate-intensity stretching may not elicit a conditioned pain modulation response possibly because the stretch was not intense enough to be perceived as painful.

Ozone therapy by rectal insufflation in dogs: safety and oxidative stress - a randomized cross-over study.

Ozone therapy acts in the body inducing controlled oxidative stress, thereby improving the antioxidant, immune and circulatory responses. However, very little is known about how this therapy affects oxidative stress indicators in dogs. We aimed to assess the clinical, hematological, biochemical and oxidative stress parameters of healthy dogs subjected to ozone therapy and oxygen therapy by rectal insufflation. Ten healthy dogs were allocated into three experimental groups in a cross-over design: control, without intervention; ozone, which received 100µg of O3/kg through rectal insufflation; and oxygen, which received an ozone-equivalent volume of medicinal O2 through rectal insufflation. Dogs received four applications weekly and were followed up until the seventh week. Ozone therapy significantly increased the weight, mean corpuscular volume and mean platelet volume and decreased total cholesterol of treated dogs. Regarding oxidative stress, ozone therapy reduced total antioxidant capacity by ferric reduction (TAC-FRAP) in D7 compared with baseline and the control, significantly increased total antioxidant capacity by cupric reduction (TAC-CUPRAC) in D42 and D49 compared with the control group, caused an increase in uric acid compared with the oxygen group and decreased lipid peroxidation on D21 compared with the control group. In conclusion, ozone therapy through rectal insufflation causes transient oxidative stress followed by an antioxidant response and discreetly interferes with a few clinical, hematological and biochemical variables in healthy dogs, although variables still remained within the reference ranges for the species, thus proving the safety of the therapy. Furthermore, oxygen therapy causes oxidative stress without inducing a subsequent antioxidant response.

Comparison of a portable, pneumotach flow-sensor–based spirometer (Spirofy™) with the vitalograph alpha Touch™ spirometer in evaluating lung function in healthy individuals, asthmatics, and COPD patients—a randomized, crossover study

BackgroundSpirofy™ is India’s first portable, pneumotach flow-sensor-based digital spirometer developed to diagnose asthma and chronic obstructive pulmonary disease (COPD). In this study, we compared the performance of the Spirofy™ device with that of the Vitalograph Alpha Touch™ spirometer in measuring the lung capacities of healthy individuals, asthmatics, and COPD patients. We also assessed the inter-device variability between two Spirofy™ devices.MethodsIn a randomized, three-way crossover, open-label study, we measured the differences in forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) between the Spirofy™ and Vitalograph Alpha Touch™ spirometers. A proportion of the FEV1/FVC ratio distribution of < 0.7 was used to compare the diagnostic accuracies of the Spirofy™ with Vitalograph™ Alpha Touch™ spirometers.ResultsNinety subjects participated in this study. The mean ± SD FVC values obtained from the Spirofy™ 1, Spirofy™ 2, and Vitalograph Alpha Touch™ devices were 2.60 ± 1.05 L, 2.64 ± 1.04 L, and 2.67 ± 1.04 L, respectively. The mean ± SD FEV1 values obtained from the Spirofy™ 1, Spirofy™ 2, and Vitalograph Alpha Touch™ devices were 1.87 ± 0.92 (L), 1.88 ± 0.92 (L), and 1.93 ± 0.93 (L), respectively. A significant positive correlation was found between the FVC and FEV1 values recorded by Vitalograph Alpha Touch™, Spirofy™ 1, and Spirofy™ 2. As compared to Vitalograph Alpha Touch™, the Spirofy™ device showed good sensitivity (97%), specificity (90%), and overall accuracy (93.3%) at an FEV1/FVC ratio < 0.7. No inter-device variability was observed between the two Spirofy™ devices.ConclusionSpirofy™ is a portable and easy-to-use device and is as accurate as the standard Vitalograph Alpha Touch™ spirometer for the diagnosis of COPD and asthma.Trial registrationCTRI/2021/09/036492 (Clinical Trials Registry - India)